The reading requirements necessary for preparation of Professor Frederick Carrick's lecture on the Brain and its environment are taken from Kandel, Schwartz and Jessel, Principles of Neural Science, IIIrd edition

The reading requirements necessary for preparation of Professor Frederick Carrick's lecture on the Brain and its environment are taken from Kandel, Schwartz and Jessel, Principles of Neural Science, IIIrd edition.

Pages 2-16

Pages 275-282

Pages 287-293

Pages 296-308

Pages 359-365

Pages 501-510

Pages 533-546

Pages 610-624

The following references were utilized By Professor Frederick Carrick

in preparation of his lecture on the Brain and it's environment.

1. Adle Biassette, H.; Bourhy, H.; Gisselbrecht, M.; Chretien, F.;

Wingertsmann, L.; Baudrimont, M.; Rotivel, Y.; Godeau, B.; Gray,

F. Rabies encephalitis in a patient with AIDS: a

clinicopathological study. Acta-Neuropathol-Berl. 1996 Oct;

92(4): 415-20; ISSN: 0001-6322.

GERMANY. A 46-year-old man was bitten by a dog in Mali;

anti-rabies vaccination was incomplete. Three months later he

was admitted to hospital with fever and diarrhea. Human

immunodeficiency virus (HIV) serology was positive and CD4

count was 70/mm3. His status worsened rapidly with

confusion hydrophobia and hypersialorrhea. Despite anti-rabies

serotherapy and vaccination, he died suddenly 12 days after

admission. Immunofluorescence on cerebral tissue samples

established rabies encephalitis. Neuropathology showed mild

encephalitis with occasional Babes nodules and rare

perivascular mononuclear cuffs. Intraneuronal Negri inclusion

bodies were remarkably diffuse and abundant. They were

clearly demonstrated by immunocytochemistry and electron

microscopy. Apoptotic neurons were identified in the brain

stem and hippocampus in the vicinity of inflammatory foci. In

contrast, apoptosis could not be demonstrated in non-

inflammatory areas, even where Negri bodies were numerous.

There was no associated HIV encephalitis or opportunistic

infection. The occurrence of rabies encephalitis in AIDS

represents a random association, but is probably not

exceptional as rabies is endemic in many countries and the

AIDS epidemic is spreading worldwide. In this case, although

the incubation duration and clinical presentation were

comparable to those in classical rabies the T-cell-mediated

immunosuppression may account for the weak inflammatory

reaction and unusually abundant viral multiplication. This

observation confirms that all those at risk for rabies,

particularly immunocompromised patients, should receive

complete anti-rabies treatment including vaccines and

specific immunoglobulins, as soon as possible after infection..

2. al Hussain, S.; al Jomard, R. Morphology of neurons in the anterior

hypothalamic area and supraoptic hypothalamic nucleus of the

adult human brain. Ital-J-Neurol-Sci. 1996 Aug; 17(4): 261-6;

ISSN: 0392-0461.

ITALY. Morphological features of neuronal cell types in the

anterior hypothalamic area (AHA) and supraoptic hypothalamic

nucleus (SON) of the adult human brain were analysed in Golgi

impregnated preparations. Four neuronal cell types were

described for the first time in these human nuclei. Type I

neurons were found in both the AHA and SON, while the other

three cell types (types II-IV) were found only in the SON. Type

I neurons had elongated, triangular or multipolar somata,

which emitted 2-5 sparsely branching primary dendrites with

a moderate number of fine spines. Also many of type I neurons

in the AHA had thin dendritic side-branches. Type II neurons

had round or fusiform somata, and two occasionally branching

primary dendrites. Type III neurons were multipolar neurons

with 3-5 densely spined and sparsely branching dendrites.

Their axons had collaterals. Type IV neurons had very small

ovoid somata with one smooth and unbranched primary

dendrite. The neurons in the human AHA and SON were similar

to those observed in the same areas in other mammalian

species, except for the very small neurons in the SON and the

thin dendritic side-branches of type I neurons in the AHA, that

had not been previously described.

3. Alonso, J.; Rovira, A.; Capellades, J.; Ocana, I.; Rio, J.; Wicklow, K.;

Sauter, R.; Gili, J. [Cerebral proton spectroscopy of people

infected with the human immunodeficiency virus].

Espectroscopia de proton en el cerebro de personas infectadas

por el virus de la inmunodeficiencia humana. Med-Clin-Barc.

1996 Sep 28; 107(10): 361-5; ISSN: 0025-7753.

SPAIN. BACKGROUND: This article presents a combined

magnetic resonance imaging and proton spectroscopy protocol

(MRI/1H-MRS) applied to study the brain of human

immunodeficiency virus (HIV) infected patients. The

spectroscopic results were compared with clinical and

radiological parameters. PATIENTS AND METHODS: The proton

spectra of 57 HIV patients and 20 control subjects were

obtained from a volume of interest of 8 cm3 located in the

parietooccipital region of the brain that did not include any

focal lesion. The resonance areas due to N-acetyl aspartate

(NAA), creatine (Cr) and choline (Cho) were obtained. The MRI

exam allowed us to determine the presence of focal or diffuse

lesions and the degree of atrophy. Finally, the clinical

exploration included the performance of a Mini-Mental test.

The NAA/Cr, NAA/Cho and Cho/Cr ratios were correlated with

clinical characteristics, the result of the Mini-Mental test,

the presence of lesions and the degree of atrophy. RESULTS:

There were altered spectral patterns in a volume of the brain

that did not contain any focal lesion. The decrease in the

NAA/Cr or NAA/Cho ratios was significative when considering

the presence of atrophy, the existence of signs of cognitive

deficiencies or the diagnosis of AIDS-dementia complex.

CONCLUSIONS: The spectral changes found in the present study

suggest the existence of neuronal lesions that would be due to

the HIV-infection. A combined MRI/1H-MRS study may provide

a more complete information about the neurological

impairment by HIV and could constitute a marker of AIDS-

dementia complex.

4. Anand, P.; Parrett, A.; Chadwick, L.; Hamlyn, P. Nerve growth

factor concentrations in human cerebral blood vessels [letter].

J-Neurol-Neurosurg-Psychiatry. 1997 Feb; 62(2): 199-200;

ISSN: 0022-3050.

ENGLAND. 0.

5. Annunziato, P. W.; Gershon, A. Herpes simplex virus infections.

Pediatr-Rev. 1996 Dec; 17(12): 415-23; quiz 424; ISSN: 0191-

9601.

UNITED-STATES.

6. Baker, H. F.; Ridley, R. M. What went wrong in BSE? From prion

disease to public disaster. Brain-Res-Bull. 1996; 40(4): 237-

44; ISSN: 0361-9230.

UNITED-STATES. The recent report of 10 cases of a new

variant of Creutzfeldt-Jakob disease (CJD) which could be

related to bovine spongiform encephalopathy (BSE) has

precipitated alarm throughout Europe. The beef trade in the UK

has collapsed and the European beef market has been seriously

damaged. What went wrong? Much of the difficulty of handling

the BSE epidemic arose from the 4-5 year incubation period

which made it difficult to ascertain whether measures taken

to contain the epidemic had been effective. Public

consternation and scientific equivocation arose because these

prion diseases are unlike any other group of infectious

diseases. Rather than being caused by a conventional micro-

organism, the primary pathogenic event consists of the

transformation of a normal protein (the prion protein) into an

abnormal form, which can transmit disease. Prion disease is

endemic in humans and sheep where it is associated with

polymorphisms or mutations within the prion protein gene.

Although the disease in these cases arises spontaneously, it

produces an infectious prion protein. Under certain

circumstances, abnormal prion protein contaminates other

animals or humans resulting in epidemics of acquired prion

disease. This review describes the events of the BSE epidemic

and considers the difficulties in assessing the current risk to

human health.

7. Barton, A. J.; Crook, B. W.; Karran, E. H.; Brown, F.; Dewar, D.; Mann,

D. M.; Pearson, R. C.; Graham, D. I.; Hardy, J.; Hutton, M.; Duff, K.;

Goate, A. M.; Clark, R. F.; Roberts, G. W. Alteration in brain

presenilin 1 mRNA expression in early onset familial

Alzheimer's disease. Neurodegeneration. 1996 Sep; 5(3): 213-

8; ISSN: 1055-8330.

ENGLAND. The expression of the presenilin 1 (PS-1) gene has

been investigated by in situ hybridization in early onset

familial Alzheimer's disease (FAD), late onset Alzheimer's

disease (AD) and normal control brain. Mutations in this gene

are responsible for chromosome 14-linked FAD. We have found

that presenilin 1 mRNA is present throughout the human brain

with a distribution consistent with both a glial and neuronal

localization. The in situ hybridization pattern was similar for

the controls, the early onset FAD cases and the late onset AD

cases. However, one of the two forms of the mRNA for PS-1,

the long form (which contains a sequence encoding a four

amino acid (VRSQ) insert at its 5' end) was significantly

reduced in early onset FAD brain compared with late onset AD.

We suggest that this long transcript may alter the normal

pathway for processing of amyloid precursor protein, the

protein which appears to be central in the pathogenesis of AD..

0; 0; 0.

8. Bauer, L. O. Resting hand tremor in abstinent cocaine-dependent,

alcohol-dependent, and polydrug-dependent patients. Alcohol-

Clin-Exp-Res. 1996 Oct; 20(7): 1196-201; ISSN: 0145-6008.

UNITED-STATES. Laboratory studies of cocaine-exposed

rodents, and positron emission tomographic studies of human

cocaine abusers have suggested that chronic cocaine abuse

downregulates dopaminergic function in the basal ganglia. The

present study sought to provide behavioral evidence for this

phenomenon by demonstrating enhanced levels of resting hand

tremor among patients with previous histories of cocaine

dependence. to determine the specificity of the phenomenon,

patients with previous histories of alcohol dependence,

cocaine/alcohol codependence, and cocaine/opiate

codependence were also evaluated. Patients were assigned to

one of four groups according to DSM-IIIR diagnostic criteria:

(1) cocaine dependent (n = 19); (2) cocaine and alcohol

dependent (n = 12); (3) cocaine and opiate dependent (n = 7); (4)

alcohol dependent (n = 9). All were abstinent from their

primary drug of abuse for a period of 1 to 5 months. The three

patient groups with histories of cocaine dependence exhibited

significantly more resting hand tremor than the alcohol-

dependent and normal control groups. Furthermore, hand tremor

in the former three groups was positively related to the

number of self-reported uses of cocaine and negatively related

to the number of months of cocaine abstinence.. 0; 50-36-2.

9. Berger, D. S.; Bucher, G.; Nowak, J. A.; Gomatos, P. J. Acute primary

human immunodeficiency virus type 1 infection in a patient

with concomitant cytomegalovirus encephalitis. Clin-Infect-

Dis. 1996 Jul; 23(1): 66-70; ISSN: 1058-4838.

UNITED-STATES. We report what we believe is the first case

of primary human immunodeficiency virus type 1 (HIV-1)

infection and simultaneous cytomegalovirus (CMV)

encephalitis, which was confirmed by detection of CMV DNA in

the patient's cerebrospinal fluid with use of the polymerase

chain reaction. This coinfection had an unusual course, and the

patient's clinical status deteriorated despite administration

of combination antiretroviral therapy. The patient responded

clinically only after therapy for CMV infection was added to

his combination antiretroviral regimen. An atypical course and

duration of symptomatic primary HIV-1 infection should

suggest a possible coincident infection with other

opportunistic agents that are normally expected to cause

disease later in the course of HIV-1 infection. Current

recommendations from the Centers for Disease Control and

Prevention list CMV encephalitis as an AIDS-defining event..

0; 0.

10. Berkovic, S. F.; Kuzniecky, R. I.; Andermann, F. Human

epileptogenesis and hypothalamic hamartomas: new lessons

from an experiment of nature [editorial]. Epilepsia. 1997 Jan;

38(1): 1-3; ISSN: 0013-9580.

UNITED-STATES.

11. Berr, C.; Lafont, S.; Debuire, B.; Dartigues, J. F.; Baulieu, E. E.

Relationships of dehydroepiandrosterone sulfate in the elderly

with functional, psychological, and mental status, and short-

term mortality: a French community-based study. Proc-Natl-

Acad-Sci-U-S-A. 1996 Nov 12; 93(23): 13410-5; ISSN: 0027-

8424.

UNITED-STATES. In human beings of both sexes,

dehydroepiandrosterone sulfate (DHEAS) circulating in blood is

mostly an adrenally secreted steroid whose serum

concentration (in the micromolar range and 30-50% higher in

men than in women) decreases with age, toward approximately

20-10% of its value in young adults during the 8th and 9th

decades. The mechanism of action of DHEA and DHEAS is poorly

known and may include partial transformation into sex

steroids, increase of bioavailable insulin-like growth factor 1,

and effects on neurotransmitter receptors. Whether there is a

cause-to-effect relationship between the decreasing levels of

DHEAS with age and physiological and pathological

manifestations of aging is still undecided, but this is of

obvious theoretical and practical interest in view of the easy

restoration by DHEA administration. Here we report on 622

subjects over 65 years of age, studied for the 4 years since

DHEAS baseline values had been obtained, in the frame of the

PAQUID program, analyzing the functional, psychological, and

mental status of a community-based population in the south-

west of France. We confirm the continuing decrease of DHEAS

serum concentration with age, more in men than in women,

even if men retain higher levels. Significantly lower values of

baseline DHEAS were recorded in women in cases of functional

limitation (Instrumental Activities of Daily Living),

confinement, dyspnea, depressive symptomatology, poor

subjective perception of health and life satisfaction, and

usage of various medications. In men, there was a trend for the

same correlations, even though not statistically significant in

most categories. No differences in DHEAS levels were found in

cases of incident dementia in the following 4 years. In men

(but not in women), lower DHEAS was significantly associated

with increased short-term mortality at 2 and 4 years after

baseline measurement. These results, statistically established

by taking into account corrections for age, sex, and health

indicators, suggest the need for further careful trials of the

administration of replacement doses of DHEA in aging humans.

Indeed, the first noted results of such "treatment" are

consistent with correlations observed here between functional

and psychological status and endogenous steroid serum

concentrations.. 651-48-9.

12. Beyreuther, K.; Multhaup, G.; Masters, C. L. Alzheimer's disease:

genesis of amyloid. Ciba-Found-Symp. 1996; 199: 119-27;

discussion 127-31; ISSN: 0300-5208.

NETHERLANDS. Much of the present knowledge on the genes and

genetic processes involved in the genesis of amyloid formation

in Alzheimer's disease (AD) has come directly or indirectly

from the retrospective molecular and genetic analysis of

amyloid beta-protein (A beta or beta A4) deposits and from the

identification of genes involved in inherited susceptibility to

the disease. This analysis shows that the release and

aggregation of the A beta fragment from the amyloid precursor

protein (APP) is involved in APP (AD1), chromosome 14 (AD3),

1 (AD4) and 19(AD2) families as well as in the sporadic forms

of AD, suggesting that AD is a single disease with a common

APP/A beta amyloid pathogenesis. Synthetic A beta protein

readily forms beta sheets, filaments and amyloid at

micromolar concentrations. The principle to inhibit this

process has been worked out by our groups with A beta

variants. The N-terminal and C-terminal A beta sequences,

oxidative radicals, membrane integrity and metal ions also

affect the aggregation of A beta. Amino acid substitutions

within the A beta sequence, as occur in rodents, alter A beta

release and change the degree to which oxidation of the

peptides occurs. Transgenic approaches resulting in

overexpression of human APP have confirmed that A beta

sequence and concentration are critical prerequisites to

amyloid deposition in vivo.. 0; 0; 0.

13. Biesecker, L. G.; Abbott, M.; Allen, J.; Clericuzio, C.; Feuillan, P.;

Graham, JM Jr; Hall, J.; Kang, S.; Olney, A. H.; Lefton, D.; Neri, G.;

Peters, K.; Verloes, A. Report from the workshop on Pallister-

Hall syndrome and related phenotypes. Am-J-Med-Genet. 1996

Oct 2; 65(1): 76-81; ISSN: 0148-7299.

UNITED-STATES.

14. Biesecker, L. G.; Graham, JM Jr. Pallister-Hall syndrome. J-Med-

Genet. 1996 Jul; 33(7): 585-9; ISSN: 0022-2593.

ENGLAND.

15. Binder, J. R.; Frost, J. A.; Hammeke, T. A.; Cox, R. W.; Rao, S. M.;

Prieto, T. Human brain language areas identified by functional

magnetic resonance imaging. J-Neurosci. 1997 Jan 1; 17(1):

353-62; ISSN: 0270-6474.

UNITED-STATES. Functional magnetic resonance imaging

(FMRI) was used to identify candidate language processing

areas in the intact human brain. Language was defined broadly

to include both phonological and lexical-semantic functions

and to exclude sensory, motor, and general executive functions.

The language activation task required phonetic and semantic

analysis of aurally presented words and was compared with a

control task involving perceptual analysis of nonlinguistic

sounds. Functional maps of the entire brain were obtained from

30 right-handed subjects. These maps were averaged in

standard stereotaxic space to produce a robust "average

activation map" that proved reliable in a split-half analysis.

As predicted from classical models of language organization

based on lesion data, cortical activation associated with

language processing was strongly lateralized to the left

cerebral hemisphere and involved a network of regions in the

frontal, temporal, and parietal lobes. Less consistent with

classical models were (1) the existence of left hemisphere

temporoparietal language areas outside the traditional

"Wernicke area," namely, in the middle temporal, inferior

temporal, fusiform, and angular gyri; (2) extensive left

prefrontal language areas outside the classical "Broca area";

and (3) clear participation of these left frontal areas in a task

emphasizing "receptive" language functions. Although partly in

conflict with the classical model of language localization,

these findings are generally compatible with reported lesion

data and provide additional support for ongoing efforts to

refine and extend the classical model.

16. Bingham, P. M.; Spinner, N. B.; Sovinsky, L.; Zackai, E. H.; Chance, P.

F. Infantile spasms associated with proximal duplication of

chromosome 15q. Pediatr-Neurol. 1996 Sep; 15(2): 163-5;

ISSN: 0887-8994.

UNITED-STATES. We describe a case of infantile spasms

associated with a chromosome abnormality (supernumerary

inverted duplication of chromosome 15 [47,XX,+inv dup(15)]).

The patient was nondysmorphic and presented with mild

hypotonia and delay in acquisition of gross motor milestones

before the diagnosis of seizures at age 7 months. Additional

features included unilateral sensorineural deafness and

torticollis. Molecular cytogenetic studies confirmed that the

patient has a large inv dup(15). Inv dup(15) chromosomes are

variable with respect to the size and genetic composition of

the chromosome and in their phenotypic effects. Patients with

small inv dup(15s) may have no phenotypic abnormalities,

whereas patients with large inv dup(15s) may have multiple

abnormalities. ACTH therapy resulted in prompt remission of

seizures and resolution of EEG abnormalities. This is the

second report of a patient with IS and a supernumerary inv

dup(15). Several genes code for neurotransmitter receptor

subunits located in the duplicated region of chromosome 15,

and abnormal dosage of these genes may be involved in the

genesis of seizure activity in carriers of the inv dup(15).

Chromosome analysis may lead to a specific diagnosis in

infants with unexplained infantile spasms.. 9002-60-2.

17. Blok, B. F.; Willemsen, A. T.; Holstege, G. A PET study on brain

control of micturition in humans. Brain. 1997 Jan; 120( Pt 1):

111-21; ISSN: 0006-8950.

ENGLAND. Although the brain plays a crucial role in the control

of micturition, little is known about the structures involved.

Identification of these areas is important, because their

dysfunction is though to cause urge incontinence, a major

problem in the elderly. In the cat, three areas in the brainstem

and diencephalon are specifically implicated in the control of

micturition: the dorsomedial pontine tegmentum, the

periaqueductal grey, and the preoptic area of the

hypothalamus. PET scans were used to test whether these

areas are also involved in human micturition. Seventeen right-

handed male volunteers were scanned during the following four

conditions: (i) 15 min prior to micturition during urine

withholding: (ii) during micturition; (iii) 15 min after

micturition; (iv) 30 min after micturition. Ten of the 17

volunteers were able to micturate during scanning.

micuturition was associated with increased blood flow in the

right dorsomedial pontine tegmentum, the periaqueductal grey,

the hypothalamus and the right inferior frontal gyrus.

Decreased blood flow was found in the right anterior cingulate

gyrus when urine was withheld. The other seven volunteers

were not able to micturate during scanning, although they had

a full bladder and tried vigorously to do so. In this group,

during these unsuccessful attempts to micturate, increased

blood flow was found in the right ventral pontine tegmentum,

which corresponds with the hypothesis, formulated from

results in cats, that this area controls the motor neurons of

the pelvic floor. Increased blood flow was also found in the

right inferior frontal gyrus during unsuccessful attempts at

micturition, and decreased blood flow in the right anterior

cingulate gyrus was found during the withholding of urine. The

results suggest that, as that of the cat, the human brainstem

contains specific nuclei responsible for the control of

micturition, and that the cortical and pontine micturition

sites are predominantly on the right side.

18. Boneh, A. Protein kinase C activity, phosphate uptake and

endogenous substrate phosphorylation are altered in Zellweger

syndrome. J-Inherit-Metab-Dis. 1996; 19(5): 661-6; ISSN:

0141-8955.

NETHERLANDS. Protein kinase C (PKC) is a key enzyme in lipid-

mediated signal transduction. Regulation of PKC activation is

dependent upon the phospholipid constituents of cellular

membranes. PKC is also activated by very long-chain and long-

chain cis-unsaturated fatty acids. The present study was

undertaken as a first step towards elucidating a possible role

for PKC in the pathogenesis of Zellweger syndrome, in which

there are both perturbation of plasma membrane phospholipids

and accumulation of very long-chain fatty acids. PKC activity,

phosphate uptake and endogenous substrate phosphorylation

were examined in intact human skin fibroblasts from

Zellweger patients. PKC catalytic activity was increased in

the membranous fraction of Zellweger cells compared with

control cells, with no apparent translocation of the enzyme

from the cytosolic to the membranous compartment. Phosphate

uptake was increased in both cytosolic and membranous

fractions 2.5-fold and 4.5-fold, respectively. Several proteins

were extensively phosphorylated in Zellweger cells compared

with control cells. These findings indicate that PKC activity is

perturbed in Zellweger cells, but the exact role of PKC in

altered phosphate uptake and protein phosphorylation and its

relevance to the pathogenesis of Zellweger syndrome require

further study.. EC 2.7.1.-; 0.

19. Brandt, M. E.; Bohan, T. P.; Thorstad, K.; McCauley, S. R.; Davidson,

K. C.; Francis, D. J.; Kramer, L. A.; Fletcher, J. M. Reliability of

brain structure morphometry in hydrocephalic children using

MR images. Magn-Reson-Imaging. 1996; 14(6): 649-55; ISSN:

0730-725X.

UNITED-STATES. To assess the ability of human operators to

make decisions about region boundaries in significantly

malformed brains, we performed a study of the reliability of

morphometric measurements of specific brain structures from

MRI in children with hydrocephalus and controls. Cross-

sectional area measures of the corpus callosum, internal

capsules and centrum semiovale, and volumes of the lateral

ventricles were made in 50 children. Independent

measurements were made by two raters on T1 and T2-

weighted MR images. Pearson's correlation coefficients (r) and

intraclass correlation coefficients (ICC) between the two

rater's sets of measures were computed for each structure

across all subjects. ICCs ranged from a low of 0.7502 to a high

of 0.9895. All ICCs were significant at the p < .0001 level and

were generally less than or equal to the corresponding

Pearson's r value in every case. Therefore, the Pearson's r may

overestimate the reliability. The results of this study support

the claim that the ICC should be used rather than the Pearson's

r when assessing interater reliability in situations where

large between-group differences are present. In addition, the

results show that brains malformed by disorders, such as

hydrocephalus, can be reliably assessed using morphometric

measures of MR images.

20. Brazell, V. J. The human side of "mad cow" disease. RN. 1997 Jan;

60(1): 32-4; quiz 35; ISSN: 0033-7021.

UNITED-STATES.

21. Brugere Picoux, J.; Lasmezas, C.; Deslys, J. P.; Adjou, K.; Rerat, A.;

Dormont, D. [Bovine spongiform encephalopathy. Second update

of data collected since the report of February 6, 1996].

Encephalopathie spongiforme bovine. Deuxieme mise au point

des donnees recueillies depuis le voeu du 6 fevrier 1996. Bull-

Acad-Natl-Med. 1996 Jun; 180(6): 1443-9; discussion 1450-4;

ISSN: 0001-4079.

FRANCE. The observation in 1995 and 1996 of 12 cases of a

new variant of Creutzfeldt-Jakob disease (V-CJD) in U.K.

suggested a possible relation between this human cases and

bovine spongiform encephalopathy (BSE). Recent papers about

this topic are reviewed: BSE transmission to macaques,

transmission of scrapie with embryo transfer, incidence of

maternal transmission, PrP protein released by platelets,

diagnostic test by detection of PrP protein in tissues of sheep,

epidemiology of BSE, french regulations, identification of

cattle in U.K.

22. Brugere Picoux, J.; Rerat, A. [Bovine spongiform encephalopathy.

Review of data collected since the statement of February 6,

1996]. Encephalopathie spongiforme bovine. Mise au point des

donnees recueillies depuis le voeu du 6 fevrier 1996. Bull-

Acad-Natl-Med. 1996 May; 180(5): 1007-12; discussion 1012-

5; ISSN: 0001-4079.

FRANCE. The observation in 1995 and 1996 of 10 cases of a

new variant of Creutzfeldt-Jakob disease (V-CJD) in U.K.

suggested a possible relation between this human cases and

bovine spongiform encephalopathy (BSE). Recent papers about

this topic are reviewed : hypothesis of a possible genetic link

between man and cattle, hypothesis of a acquired resistance

against the agent of BSE after a previous infection by a less

virulent agent of ovine origin, importance of polymorphism at

codon 129 according to the hypothesis of a virus-induced

amyloidosis, diagnostic test with cerebrospinal fluid,

epidemiology of BSE and prediction of future BSE spread.

23. Bruning, R.; Wu, R. H.; Deimling, M.; Porn, U.; Haberl, R. L.; Reiser, M.

Diffusion measurements in the ischemic human brain with a

steady-state sequence. Invest-Radiol. 1996 Nov; 31(11): 709-

15; ISSN: 0020-9996.

UNITED-STATES. RATIONALE AND OBJECTIVES: The authors

evaluate the clinical usefulness of a diffusion-weighted

steady-state free-precession (SSFP) sequence to detect acute

and subacute ischemic changes. METHODS: Twenty-four

patients were examined on a 1.5-tesla scanner, using a SSFP-

sequence (repetition time [TR]/ echo time [TE] = 22/3-8

mseconds). The slice thickness was 5 mm, 10 averages, 57

seconds per slice. The diffusion gradient strength was 23

millitesla/m, with b-values from 165 to 598 seconds/mm2.

Diffusion-weighted images (DWI) were compared with T2-

weighted images. RESULTS: The diffusion-weighted SSFP

sequence produced diagnostic quality images in 23 of 24

patients. Diffusion depicted (group 1: 0-12 hours) more acute

lesions (3 of 6) than T2-weighted images (2 of 6); the mean

lesion diameter depicted by diffusion was 10.9 mm (standard

deviation [SD], 12.3) and in T2-weighted images was 4.7 mm

(SD 6.8). A significant correlation (P < 0.017) in subacute

lesions was found when diffusion was compared with turbo

spin echo (mean size difference/T2 = 18.5/17.5 mm, SD

13.2/12.2). CONCLUSIONS: The diffusion-weighted SSFP-

sequence is more sensitive in acute ischemia and delineates

likewise in subacute ischemia, when compared with T2-

weighted imaging.

24. Butterworth, R. J.; Wassif, W. S.; Sherwood, R. A.; Gerges, A.;

Poyser, K. H.; Garthwaite, J.; Peters, T. J.; Bath, P. M. Serum

neuron-specific enolase, carnosinase, and their ratio in acute

stroke. An enzymatic test for predicting outcome? Stroke.

1996 Nov; 27(11): 2064-8; ISSN: 0039-2499.

UNITED-STATES. BACKGROUND AND PURPOSE: Few admission

variables adequately predict neuronal damage and prognosis in

individual patients after stroke. Therefore, there is a need for

a reliable non-invasive surrogate measure of clinical outcome.

METHODS: We have developed a surrogate measure of stroke

outcome using the ratio of serum neuron-specific enolase

(NSE) to human serum carnosinase (HSC) in 124 patients with

acute ischemic or hemorrhagic stroke and 61 matched control

subjects. Serum NSE is known to rise and HSC to fall after

neuronal injury such as cerebral ischemia. RESULTS: Serum NSE

levels were significantly higher and HSC levels lower in the

patient group. The NSE/HSC ratio was elevated in patients

with stroke: median (semiquartile) hemorrhages, 0.072

(0.033); infarcts, 0.039 (0.026); and control subjects, 0.019

(0.014), P = .0001. Patients with a primary intracerebral

hemorrhage had nonsignificantly higher ratios than those with

an infarct (P = .082). The NSE/HSC ratio was significantly

associated with 90-day outcome measured in two out of three

disability and handicap scales: modified Barthel Index (rs = -

.34, P = .001), modified Rankin Scale (rs = .30, P = .002), and

Lindley Score (rs = .19, P = .057). Patients who died or were

institutionalized had higher ratios than those who were

discharged home: 0.069 (0.043) versus 0.038 (0.024), P = .011.

Correlations between the NSE/HSC ratio and outcome were

comparable to those between patient age or consciousness

level on admission and clinical outcome. CONCLUSIONS: We

believe that measurement of NSE, HSC, or their ratio may be

useful in the assessment of patients with acute stroke with

respect to diagnosis and prediction of clinical outcome.. EC

3.4.13.; EC 3.4.13.3; EC 4.2.1.11.

25. Byrum, C. E.; MacFall, J. R.; Charles, H. C.; Chitilla, V. R.; Boyko, O.

B.; Upchurch, L.; Smith, J. S.; Rajagopalan, P.; Passe, T.; Kim, D.;

Xanthakos, S.; Ranga, K.; Krishnan, R. Accuracy and

reproducibility of brain and tissue volumes using a magnetic

resonance segmentation method. Psychiatry-Res. 1996 Oct 7;

67(3): 215-34; ISSN: 0165-1781.

IRELAND. Magnetic resonance (MR) imaging now allows the

qualitative and quantitative assessment of the human brain in

vivo. As MR imaging resolution has improved, precise

measurement of small brain structures has become possible.

Methods of measuring brain regions from MR images include

both manual and semiautomated methods. Despite the

development of numerous volumetric methods, there have been

only limited attempts so far to evaluate the accuracy and

reproducibility of these methods. In this study we used

phantoms to assess the accuracy of the segmentation process.

Our results with simple and complex phantoms indicate an

error of 3-5% using either manual or semiautomated

techniques. We subsequently used manual and semiautomated

volumetric methodologies to study human brain structures in

vivo in five normal subjects. Supervised segmentation is a

semiautomated method that accomplishes the division of MR

images into several tissue types based on differences in signal

intensity. This technique requires the operator to manually

identify points on the MR images that characterize each tissue

type, a process known as seeding. However, the use of

supervised segmentation to assess the volumes of gray and

white matter is subject to pitfalls. Inhomogeneities of the

radiofrequency or magnetic fields can result in

misclassification of tissue points during the tissue seeding

process, limiting the accuracy and reliability of the

segmentation process. We used a structured seeding protocol

that allowed for field inhomogeneity that produced reduced

variation in measured tissue volumes. We used repeated

segmentations to assess intra- and inter-rater reliability, and

were able to measure small and large regions of interest with

a small degree of variation. In addition, we demonstrated that

measurements are reproducible with repeat MR acquisitions,

with minimal interscan variability. Segmentation methods can

accurately and reliably measure subtle morphometric changes,

and will prove a boon to the study of neuropsychiatric

disorders.

26. Chiba, H. [Physiology and pathology of the lipid transport in the

brain]. Rinsho-Byori. 1996 Mar; 44(3): 231-6; ISSN: 0047-1860.

JAPAN. Apolipoprotein E is the major lipid carrier protein in

the brain. This protein is contained in HDL1-like particles in

human and rat cerebrospinal fluid. Cerebrospinal fluid

apolipoprotein metabolism is resistant to the alteration in

plasma lipoprotein metabolism and to age-related changes. In

a patient with multiple sclerosis, immunoreactive

apolipoprotein E was seen in astrocytes and macrophages in

the brain section with a pathological change, indicating that

apolipoprotein E has a significant role in the lipid

redistribution process after demyelination. The epsilon4 allele

is more frequent in Japanese patients with Alzheimer's

disease than in control, as well as Caucasians, suggesting the

significant contribution of the epsilon4 allele to the

pathogenesis of the disease.. 0; 0.

27. Chrzanowska, K. H. [Microcephaly with chromosomal instability

and immunodeficiency--Nijmegen syndrome]. Maloglowie z

niestabilnoscia chromosomowa i zaburzeniami odpornosci--

zespol Nijmegen. Pediatr-Pol. 1996 Mar; 71(3): 223-34; ISSN:

0031-3939.

POLAND. The Nijmegen breakage syndrome (NBS) is a rare

autosomal recessive disease, which belongs to the family of

genetically determined instability syndromes and to the

growing category of ataxia telangiectasia (AT)--related

disorders. The main manifestations include pronounced

microcephaly with mental retardation in most patients, "bird-

like" facies, growth retardation, immunodeficiency,

chromosome instability with multiple chromosome 7 and 14

rearrangements, hypersensitivity to ionizing radiation and

normal AFP level. In light of high predisposition to malignancy,

an accurate diagnosis is very important for the patient.. 0.

28. Cinque, P.; Vago, L.; Dahl, H.; Brytting, M.; Terreni, M. R.; Fornara,

C.; Racca, S.; Castagna, A.; Monforte, A. D.; Wahren, B.; Lazzarin,

A.; Linde, A. Polymerase chain reaction on cerebrospinal fluid

for diagnosis of virus-associated opportunistic diseases of

the central nervous system in HIV-infected patients. AIDS.

1996 Aug; 10(9): 951-8; ISSN: 0269-9370.

UNITED-STATES. OBJECTIVE: To assess the diagnostic

reliability of polymerase chain reaction (PCR) on cerebrospinal

fluid (CSF) for virus-associated opportunistic diseases of the

central nervous system (CNS) in HIV-infected patients. DESIGN:

CSF samples from 500 patients with HIV infection and CNS

symptoms were examined by PCR. In 219 patients the PCR

results were compared with CNS histological findings.

METHODS: Nested PCR for detection of herpes simplex virus

(HSV) type 1 or 2, varicella zoster virus (VZV),

cytomegalovirus (CMV), Epstein-Barr virus (EBV), human

herpesvirus 6 (HHV-6), and JC virus (JCV) DNA.

Histopathological examination of CNS tissue obtained at

autopsy or on brain biopsy. RESULTS: DNA of one or more

viruses was found in CSF in 181 out of 500 patients (36%;

HSV-1 2%, HSV-2 1%, VZV 3%, CMV 16%, EBV 12%, HHV-6 2%,

and JCV 9%). Among the 219 patients with histological CNS

examination, HSV-1 or 2 was detected in CSF in all six

patients (100%) with HSV infection of the CNS, CMV in 37 out

of 45 (82%) with CMV infection of the CNS, EBV in 35 out of 36

(97%) with primary CNS lymphoma, JCV in 28 out of 39 (72%)

with progressive multifocal leukoencephalopathy.

Furthermore, HSV-1 was found in one, VZV in four, CMV in

three, EBV in three, HHV-6 in seven, and JCV in one patient

without histological evidence of the corresponding CNS

disease. CONCLUSIONS: CSF PCR has great relevance for

diagnosis of virus-related opportunistic CNS diseases in HIV-

infected patients as demonstrated by its high sensitivity,

specificity, and the frequency of positive findings.. 0; 0.

29. Colder, B. W.; Wilson, C. L.; Frysinger, R. C.; Chao, L. C.; Harper, R.

M.; Engel, J. Jr. Neuronal synchrony in relation to burst

discharge in epileptic human temporal lobes. J-Neurophysiol.

1996 Jun; 75(6): 2496-508; ISSN: 0022-3077.

UNITED-STATES. 1. Synchronous interactions between neurons

in mesial temporal structures of patients with complex

partial seizures were studied using cross-correlation

analyses. We recorded spontaneous activity from 293 neurons

in 24 patients during the interictal state. Patients had depth

microelectrodes chronically implanted in amygdala,

hippocampal formation, and parahippocampal gyrus to record

epileptic activity. One hundred twenty-five cells were

recorded from the temporal lobe commonly initiating seizures

(ipsilateral temporal lobe), and 168 cells from the

contralateral temporal lobe. Eight hundred forty-three cross-

correlograms were constructed between all pairs of

simultaneously recorded neurons. Cross-correlogram peaks or

troughs that exceeded confidence limits within 200 ms of the

origin were considered evidence of synchronous neuronal

interaction. 2. Synchronous neuronal interactions were

observed in 223 of 843 cross-correlograms. Eighty-six percent

of these 223 cross-correlograms showed significant central

peaks (peak interactions), suggesting excitatory interactions,

whereas the remainder displayed significant central troughs

(trough interactions), suggesting inhibitory interactions. 3.

Cross-correlograms constructed using cells from the

ipsilateral temporal lobe (ipsilateral cross-correlograms)

were more likely to display significant central troughs

(14/262) than cross-correlograms constructed using cells

from the contralateral temporal lobe (6/376; contralateral

cross-correlograms). Similarly, cross-correlograms

constructed using one cell from each hemisphere (11/205;

bilateral cross-correlograms) were also more likely to display

significant central troughs (trough interactions) than

contralateral cross-correlograms. Both ipsilateral (77/262)

and contralateral cross-correlograms (102/376) were more

likely to display significant central peaks (peak interactions)

than bilateral cross-correlograms (13/205). 4. Cells from

different structures in the ipsilateral temporal lobe were

more likely to display significant trough interactions (10/

114) than neurons in different contralateral structures. We

also compared the proportion of significant peak interactions

between cells within the ipsilateral and contralateral sides of

each structure. Neurons in the contralateral entorhinal cortex

were more likely to show peak interactions (21/55) than cells

from the ipsilateral entorhinal cortex (3/31). Also, cells in

the ipsilateral presubiculum showed a higher proportion of

peak interactions (9/16) than their contralateral homologues

(5/30). 5. Neuronal burst discharges were defined as three or

more action potentials (or spikes) separated by interspike

intervals of < or = 30 ms, or two spikes separated by an

interval of < or = 15 ms. The contribution of burst discharge to

synchronous peak interaction was compared between temporal

lobes. Cells used to construct ipsilateral cross-correlograms

displaying significant central peaks (n = 154) were found to

have significantly reduced burst discharge contributions to the

observed synchronous peaks in comparison with their

contralateral homologues (n = 204). When cross-correlograms

were separated by regions, burst discharge contributions to

synchronous peak interactions between cells in the ipsilateral

hippocampus (n = 72) were significantly smaller than the

contributions from cells in the contralateral hippocampus (n =

44). 6. The results suggest that in the interictal state,

synchronous neuronal burst discharge is not a distinguishing

feature of epileptogenic regions of patients with complex

partial seizures, but inhibitory neuronal interactions are

increased in regions of seizure initiation. Increases in the

strength and spread of local inhibition in seizure initiating

regions in these patients may result in a greater proportion of

inhibitory interactions and could also cause increased

synchrony between isolated action potentials.(ABSTRACT

TRUNCATED).

30. Connors, M. H.; Boggan, J. E.; Chong, B.; Kollipara, S. Expansion and

shrinkage of central nervous system tumor coinciding with

human growth hormone therapy: case report. Neurosurgery.

1996 Dec; 39(6): 1243-5; discussion 1245-6; ISSN: 0148-

396X.

UNITED-STATES. OBJECTIVE AND IMPORTANCE: The influence

of human growth hormone (hGH) therapy on the recurrence

rates of childhood central nervous system tumors is

controversial. Because growth hormone has the ability to

increase cell proliferation, it is recommended that hGH

therapy wait until central nervous system lesions are inactive

and antitumor therapy complete, usually 1 to 2 years. CLINICAL

PRESENTATION: We report the enlargement and decrease in size

of a hypothalamic pilocytic astrocytoma in a 12-year-old boy

after two trials of hGH. Partial resection and radiation of the

tumor were performed at 3 years of age, with no change noted

over the next 9 years. His height was less than the 5th centile

with midparental height at the 90th to 95th centiles. Growth

velocity was 3.3 cm/yr. Bone age was normal and there were

no signs of puberty. There was no GH response to clonidine and

L-dopa testing. INTERVENTION: Volume measurements were

performed on gadolinium enhanced tumor images. Growth rate

increased to 11.7 cm and the tumor volume increased 230%

over the 12 months of hGH therapy. Significant tumor

shrinkage (42%) and growth deceleration occurred within the 3

month interval of stopping hGH. Tumor volume again increased

(134%) and decreased (22%) after restarting and then stopping

hGH. No evidence of tumor necrosis or alteration in ventricular

size was found. The patient was asymptomatic. CONCLUSION:

These observations indicate that tumor size change is

associated with the metabolic response to hGH therapy. It is

unclear whether the volume increase represents altered blood-

brain or selective blood-tumor barrier permeability, growth

factor receptors, and/or tumor cell growth.. 12629-01-5.

31. Coria, F.; Cuadrado, N. [Genetic neuroepidemiology].

Neuroepidemiologia genetica. Neurologia. 1995 Dec; 10 Suppl 1:

50-5; ISSN: 0213-4853.

SPAIN. Many human diseases result from the combined effect

of several genetic and non genetic factors. Thanks to the

development of powerful tools for molecular analysis,

researchers in recent years have begun to uncover the genes

behind such multifactorial neurologic and systemic disorders

as Alzheimer's and Parkinson's diseases and diabetes. Likewise

investigators have been able to confirm that the course of

these diseases and their clinical manifestations depend on the

concurrence in the same individual of specific genetic

variations. Because each gene confers a certain degree of

predisposition to a specific disease, they are therefore called

susceptibility genes. The search for and analysis of

susceptibility genes in defined populations is termed genetic

epidemiology. This multidisciplinary science is providing

valuable data that further our understanding and ability to

diagnose of disorders of the nervous system. It also enables us

to predict the clinical course of disease in a given patient

with a high degree of reliability, even when no clinical signs

are yet evident.. 0; 0; 0.

32. Corrigan, F. M.; French, M.; Murray, L. Organochlorine compounds in

human brain. Hum-Exp-Toxicol. 1996 Mar; 15(3): 262-4; ISSN:

0960-3271.

ENGLAND. Having observed polychlorinated biphenyls (PCBs) in

brain tissue obtained post mortem from two men we have

carried out a study of organochlorine compounds in frontal

cortex from patients with Parkinson's disease (PD) and from

controls. No PCBs were found in any of those samples. There

was no difference in the concentration of the DDT metabolite

pp'-DDE in the PD brain samples. Dieldrin (HEOD) was

significantly decreased in PD brain when analysed by lipid

weight. While these findings would not support the hypothesis

that PCBs may contribute to the development of Parkinson's

disease in humans it remains possible that they may cause

damage to the basal ganglia before being displaced from brain

tissue.. 0; 50-29-3; 60-57-1.

33. Costa, A.; Benedetto, C.; Fabris, C.; Giraudi, G. F.; Testori, O.;

Bertino, E.; Marozio, L.; Varvello, G.; Arisio, R.; Ariano, M.;

Emanuel, A. Cortisol in human tissues at different stages of

life. J-Endocrinol-Invest. 1996 Jul; 19(7): 463-71; ISSN:

0391-4097.

ITALY. Aim of the work was to measure the cortisol level in

human tissues at different stages of life, by means of

radioimmunoassay and by chromatography. Viable samples of

13 different tissues were obtained during surgical

intervention from 30 to 70 years old patients of either sex.

Mean tissue cortisol concentration was 78 +/- 35 ng/g,

ranging from 20 +/- 10 ng/g in the thyroid to 124 +/- 76 ng/g

in the kidney. Similar values were measured in the

corresponding tissues from not decayed corpses, so that paired

values could be mediated. However the pancreas, and corrupted

autopsy tissues, gave nil or exceedingly high cortisol

concentration values; in some cases, opposite extreme values

were measured in different organs of the same body. Cortisol

concentration was also measured in 11 sound different tissues

of spontaneously aborted or stillbirth fetuses, between 16 and

36 weeks of gestation. Mean value was 63 +/- 27 ng/g, ranging

from 30 +/- 25 ng/g in the liver to 104 +/- 52 ng/g in the

lungs. Also in fetuses nil or exceedingly high cortisol values

occurred in altered tissues. One hundred and fourteen samples

of limbs and carcasses of 7 to 12 gestational weeks embryos,

obtained from voluntary abortions, were also examined: 20%

gave nil result, in the remaining mean cortisol concentration

was 32 ng/g. In 33 samples of embryos' mixed viscera, RIA and

chromatography gave unreliable exceedingly high values. The

nil and the exceedingly high values measured in the altered

autoptic tissue specimens were inconsistent with the cortisol

blood level measured in the patients, as were those measured

in embryonic tissues with the acknowledged blood and

adrenals cortisol levels at that stage of life. Thus cortisol

may be measured by RIA and by chromatography in sound

tissues, while the values obtained in the pancreas, in

corrupted tissues, and in embryonal viscera do not represent

the hormonal milieu, but are likely artifacts due to

impeachment of the diagnostic system.. 50-23-7.

34. Coull, J. T.; Frith, C. D.; Frackowiak, R. S.; Grasby, P. M. A fronto-

parietal network for rapid visual information processing: a

PET study of sustained attention and working memory.

Neuropsychologia. 1996 Nov; 34(11): 1085-95; ISSN: 0028-

3932.

ENGLAND. The rapid visual information processing (RVIP) task,

a test of sustained attention which also requires working

memory for its successful execution, has been used in a

number of human psychopharmacological studies. Single digits

are presented in quick succession (100 or 200 digits/min) on a

computer screen, and target sequences of numbers must be

detected with a button press. Although previous neuroimaging

studies have implicated the frontal and parietal cortices in

performance of simple sustained attention tasks, the

neuroanatomical substrates of RVIP performance are not yet

known. This information would prove invaluable in the

interpretation of drug effects on this task, possibly

delineating a neuronal network for neurotransmitter action.

Therefore, this study investigated the functional anatomy of

the RVIP task using positron emission tomography (PET)

derived measures of regional cerebral blood flow (rCBF) in

eight healthy volunteers. Subjects were required to perform

variants of the RVIP task which manipulated both the level of

working memory load and the speed of stimulus presentation.

Compared with a rest condition (eyes closed), the RVIP task

increased rCBF bilaterally in the inferior frontal gyri, parietal

cortex and fusiform gyrus, and also in the right frontal

superior gyrus rostrally. In comparison with a simple

sustained attention control condition, the aforementioned

right frontal activations were no longer apparent. We suggest

that these data are consistent with the existence of a right

fronto-parietal network for sustained, and possibly selective,

attention, and a left fronto-parietal network for the

phonological loop component of working memory.

35. Cox, R. W. AFNI: software for analysis and visualization of

functional magnetic resonance neuroimages. Comput-Biomed-

Res. 1996 Jun; 29(3): 162-73; ISSN: 0010-4809.

UNITED-STATES. A package of computer programs for analysis

and visualization of three-dimensional human brain functional

magnetic resonance imaging (FMRI) results is described. The

software can color overlay neural activation maps onto higher

resolution anatomical scans. Slices in each cardinal plane can

be viewed simultaneously. Manual placement of markers on

anatomical landmarks allows transformation of anatomical

and functional scans into stereotaxic (Talairach-Tournoux)

coordinates. The techniques for automatically generating

transformed functional data sets from manually labeled

anatomical data sets are described. Facilities are provided for

several types of statistical analyses of multiple 3D functional

data sets. The programs are written in ANSI C and Motif 1.2 to

run on Unix workstations.

36. De Caro, R.; Parenti, A.; Munari, P. F. Megalodolichobasilaris: the

effect of atherosclerosis on a previously weakened arterial

wall? Clin-Neuropathol. 1996 Jul; 15(4): 187-91; ISSN: 0722-

5091.

GERMANY. The morphological findings of 2 basilar artery giant

fusiform aneurysms are presented. In one case (a 63-year-old

man) the aneurysm was accidentally found at autopsy. Its wall

was mainly formed by fibrous tissue without a smooth muscle

layer and presented fragmented but still recognizable elastic

lamina. In the media there were small well-formed bony

spicules. In the other case (a 59-year-old man) the aneurysm

had broken causing subarachnoid hemorrhage. The wall showed

a marked reduction of smooth muscle cells and thinning and

fragmentation of elastic lamina. A second sacciform aneurysm

was present at the basilar tip. The review of the literature and

the morphological findings of the 2 cases, characterized by

abnormality of the portion of the basilar artery not directly

involved in the aneurysm wall, consisting of a diffuse deficit

of the tunica media and lamina elastica, might suggest that

the fusiform aspect of the aneurysm may be the result of the

degenerative effect of atherosclerosis on a cogenital,

structural or dysmetabolic, or acquired, inflammatory,

weakening of the arterial wall.

37. Dealler, S. A matter for debate: the risk of bovine spongiform

encephalopathy to humans posed by blood transfusion in the UK

[see comments]. Transfus-Med. 1996 Sep; 6(3): 217-22; ISSN:

0958-7578.

Note: Comment in: Transfus Med 1996 Sep;6(3 ):213-5.

ENGLAND. If human infection with bovine spongiform

encephalopathy (BSE) were to occur, donated peripheral blood

from humans that might have become infected from eating

adequate quantities of food containing BSE should, until

evidence is available to the contrary, be assumed to contain

the human form of the disease. The chance of disease transfer

to a blood recipient in 1995, which might in turn cause

clinical disease with an incubation period of 20 years, is

calculated. Transfusion is calculated to be a potential cause of

a maximum of only 0.2% of clinical cases of Creutzfeldt-Jakob

disease (CJD) in the UK population if the BSE epidemic were to

spread to humans. Prospective epidemiological techniques

would be unlikely to demonstrate any such minor contribution

that blood transfusion might make to CJD incidence.. 0.

38. Decruyenaere, M.; Evers Kiebooms, G.; Boogaerts, A.; Cassiman, J.

J.; Cloostermans, T.; Demyttenaere, K.; Dom, R.; Fryns, J. P.;

Van, den Berghe H. Prediction of psychological functioning one

year after the predictive test for Huntington's disease and

impact of the test result on reproductive decision making. J-

Med-Genet. 1996 Sep; 33(9): 737-43; ISSN: 0022-2593.

ENGLAND. For people at risk for Huntington's disease, the

anxiety and uncertainty about the future may be very

burdensome and may be an obstacle to personal decision

making about important life issues, for example, procreation.

For some at risk persons, this situation is the reason for

requesting predictive DNA testing. The aim of this paper is

two-fold. First, we want to evaluate whether knowing one's

carrier status reduces anxiety and uncertainty and whether it

facilitates decision making about procreation. Second, we

endeavour to identify pretest predictors of psychological

adaptation one year after the predictive test (psychometric

evaluation of general anxiety, depression level, and ego

strength). The impact of the predictive test result was

assessed in 53 subjects tested, using pre- and post-test

psychometric measurement and self-report data of follow up

interviews. Mean anxiety and depression levels were

significantly decreased one year after a good test result; there

was no significant change in the case of a bad test result. The

mean personality profile, including ego strength, remained

unchanged one year after the test. The study further shows

that the test result had a definite impact on reproductive

decision making. Stepwise multiple regression analyses were

used to select the best predictors of the subject's post-test

reactions. The results indicate that a careful evaluation of

pretest ego strength, depression level, and coping strategies

may be helpful in predicting post-test reactions,

independently of the carrier status. Test result (carrier/ non-

carrier), gender, and age did not significantly contribute to the

prediction. About one third of the variance of post-test

anxiety and depression level and more than half of the variance

of ego strength was explained, implying that other

psychological or social aspects should also be taken into

account when predicting individual post-test reactions.

39. DeMarchi, J. M.; Caskey, C. T.; Richards, C. S. Population-specific

screening by mutation analysis for diseases frequent in

Ashkenazi Jews. Hum-Mutat. 1996; 8(2): 116-25; ISSN: 1059-

7794.

UNITED-STATES. We describe a partially automated DNA

mutation assay for detecting the most frequent mutations in

the alpha-subunit of beta-hexosaminidase A, the acid beta-

glucosidase and the cystic fibrosis transmembrane

conductance regulator genes for the Ashkenazi Jewish

population. The assay detects carriers for Tay-Sachs disease,

Gaucher disease, and cystic fibrosis with sensitivities of at

least 92%, 96%, and 97%, respectively. Among 1,364 young

adults of Ashkenazic ancestry in the Dor Yeshurim community

who were tested, 52 were Tay-Sachs carriers, 110 were

Gaucher carriers, and 62 were cystic fibrosis carriers. Ten

individuals were carriers for two diseases, and three

unsuspected cases were diagnosed with Gaucher disease based

on mutation test results. In addition to Tay-Sachs mutation

data, results for hexosaminidase A activity were also

available. All of 1,254 samples normal by enzyme quantitation

were also negative for the three alpha-subunit mutations

tested, and all of 43 samples with 'inconclusive' enzyme

results were negative by DNA. Only 52 of 67 samples positive

by enzyme assay were also positive for one of the three

mutations tested for Tay-Sachs disease. The data suggest a

high degree of false positivity inherent in enzyme

identification of carriers. There are no correlative methods to

assess the sensitivity of Gaucher and CF carrier testing. The

results show that population screening can be carried out

efficiently by DNA analysis, with the accrual of carrier

information for three separate diseases conducted as a single

test. Furthermore, the DNA method for Tay-Sachs screening

appears to exceed the specificity of hexosaminidase A enzyme

testing.. EC 3.2.1.52; 0.

40. Deriu, F.; Roatta, S.; Grassi, C.; Urciuoli, R.; Micieli, G.; Passatore,

M. Sympathetically-induced changes in microvascular cerebral

blood flow and in the morphology of its low-frequency waves.

J-Auton-Nerv-Syst. 1996 Jun 10; 59(1-2): 66-74; ISSN: 0165-

1838.

NETHERLANDS. The effect of bilateral cervical sympathetic

nerve stimulation on microvascular cerebral blood flow,

recorded at various depths in the parietal lobe and in ponto-

mesencephalic areas, was investigated by laser-Doppler

flowmetry in normotensive rabbits. These areas were chosen

as representative of the vascular beds supplied by the carotid

and vertebro-basilar systems, which exhibit different degrees

of sympathetic innervation, the former being richer than the

latter. Sympathetic stimulation at 30 imp/s affects cerebral

blood flow in 77% of the parietal lobe and in 43% of the ponto-

mesencephalic tested areas. In both cases the predominant

effect was a reduction in blood flow (14.7 +/- 5.1% and 4.1 +/-

2.4%, respectively). The extent of the reduction in both areas

was less if the stimulation frequency was decreased.

Sometimes mean cerebral blood flow showed a small and

transient increase, mainly in response to low-frequency

stimulation. The morphology was analysed of low-frequency

spontaneous oscillations in cerebral blood flow, attributed to

vasomotion. Present in 41% of the tested areas (frequency 4-

12 cycles/min, peak-to-peak amplitude 10-40% of mean

value), these waves decreased in amplitude and increased in

frequency during sympathetic stimulation, irrespective of

changes in mean flow. The possibility has been proposed that

the sympathetic action on low-frequency spontaneous

oscillations may contribute to the protective influence that

this system is known to exert on the blood-brain barrier in

hypertension.

41. Desgranges, B.; Eustache, F.; Rioux, P.; de, La Sayette V.;

Lechevalier, B. Memory disorders in Alzheimer's disease and

the organization of human memory. Cortex. 1996 Sep; 32(3):

387-412; ISSN: 0010-9452.

ITALY. The Squire and Zola-Morgan parallel organization model

of the memory and the Tulving hierarchical model were

developed mainly through the study of amnesic patients. The

predictions of these two models are different, the first being

more open to double dissociations and less restrictive than the

second. Alzheimer's Disease is characterized by a differential

impairment of the memory systems and by an interindividual

variability which may take the form of dissociations between

preserved and disturbed abilities in some patients. The

objective of this study was to use the memory dysfunctions of

patients with AD to test the validity of the two models.

Analysis of the group data provided an average profile of

memory disturbance consistent both with much of the data

given in AD literature and with the two models. Using a

multiple single-case strategy, we demonstrated several

simple dissociations which are for the greater part compatible

with the two models. Two of the dissociations underline the

limits of the Tulving model, which otherwise accounts for a

lot of results. The study supports the relevance of AD for the

understanding of the cognitive architecture of the human

memory.

42. Domachowske, J. B.; Cunningham, C. K.; Cummings, D. L.; Crosley, C.

J.; Hannan, W. P.; Weiner, L. B. Acute manifestations and

neurologic sequelae of Epstein-Barr virus encephalitis in

children. Pediatr-Infect-Dis-J. 1996 Oct; 15(10): 871-5; ISSN:

0891-3668.

UNITED-STATES. BACKGROUND: Complications of Epstein-Barr

virus (EBV) infection are diverse and include a number of

neurologic manifestations such as meningitis,

meningoencephalitis, cerebellitis, cranial neuritis and others.

In general encephalitis caused by EBV in pediatric patients has

been considered a self-limited illness with few or no

sequelae. METHODS: Charts were reviewed from all patients <

18 years of age admitted to or discharged from the State

University of New York Health Science Center at Syracuse

between 1982 and 1992 with a diagnosis of encephalitis or

meningo-encephalitis. Eleven cases of EBV encephalitis

diagnosed during a 10-year period were reviewed to

characterize the clinical and laboratory findings in the acute

setting and the extent of neurologic sequelae on follow-up.

RESULTS: Acute neurologic manifestations were diverse and

included combative behavior (55%), seizures (36%), headache

(36%) and evidence of focal involvement (27%). Classic

findings of infectious mononucleosis were noted infrequently;

18% each had pharyngitis, adenopathy, positive heterophile

antibody tests or atypical lymphocytosis. Two patients (18%)

had abnormal neuroimaging studies, one in the acute stage and

the other at the time of follow-up. Seven patients (64%) had

abnormal electroencephalograms (EEGs) in the acute setting;

of these three had persistent abnormalities on follow-up.

Forty percent developed persistent neurologic abnormalities

including global impairment, perseverative autistic-like

behavior and persistent left upper extremity paresis.

CONCLUSIONS: Classic signs, symptoms and laboratory findings

in infectious mononucleosis may be absent in Epstein-Barr

virus encephalitis. Neurologic sequelae occur in a substantial

number of patients.

43. Doorduijn, J. K.; van, Lom K.; Lowenberg, B. Eosinophilia and

granulocytic dysplasia terminating in acute myeloid leukaemia

after 24 years. Br-J-Haematol. 1996 Dec 1; 95(3): 531-4; ISSN:

0007-1048.

ENGLAND. Eosinophilia of variable duration, and subsequent

progression to granulocytic sarcoma and acute myeloid

leukaemia, has been infrequently reported in the literature. We

report a patient with eosinophilia and normal cytogenetics

who, after 24 years, showed transformation to a granulocytic

sarcoma of the brain. Haematological counts were normal but

the marrow revealed the cytogenetic abnormality trisomy 8 in

25% of mitoses. Subsequently an AML-M2 developed, showing a

complex karyotype including the trisomy 8 in all metaphases.

FISH analysis combined with cytological examination

identified the trisomy 8 in blasts, eosinophils and dysplastic

granulocytes only. Thus progressive leukaemic transformation

selectively involved the myeloid compartment.

44. Drago, J.; Gerfen, C. R.; Westphal, H.; Steiner, H. D1 dopamine

receptor-deficient mouse: cocaine-induced regulation of

immediate-early gene and substance P expression in the

striatum. Neuroscience. 1996 Oct; 74(3): 813-23; ISSN: 0306-

4522.

UNITED-STATES. Psychomotor stimulants such as cocaine

alter gene expression in neurons of the striatum. Whereas

many of these effects are mediated by D1 dopamine receptors,

the involvement of other dopamine receptor subtypes or

neurotransmitters is likely. To distinguish between these

possibilities, regulation by cocaine of immediate-early genes

and genes encoding neuropeptides was analysed in mice that

lack functional D1 receptors. Gene expression was examined

with in situ hybridization histochemistry. In these animals,

cocaine failed to induce the immediate-early genes c-fos and

zif 268. In contrast, substance P expression was abnormally

increased by this drug. These results demonstrate that some of

the effects of cocaine on gene regulation are mediated via D1

receptor-dependent mechanisms, as evidenced by the absence

of immediate-early gene induction in D1-deficient mice,

whereas others also involve additional, non-D1 receptor

mechanisms, as shown for substance P expression.. 0; 0; 0; 0;

0; 0; 0; 0; 33507-63-0; 50-36-2; 74913-18-1.

45. Durand, P.; Debray, D.; Devictor, D. [Fulminant hepatitis in

children]. Les hepatites fulminantes de l'enfant. Presse-Med.

1996 Oct 19; 25(31): 1501-6; ISSN: 0755-4982.

FRANCE. Viral hepatitis are one of the main causes of

fulminant hepatic failure in children. Other causes of

fulminant hepatic failure include metabolic diseases,

especially in neonates and in infants, toxin-or drug-induced

liver injury, hematologic and immune diseases. The

spontaneous prognosis of fulminant hepatitis is poor with an

overall mortality reaching 80%. The management of children

with fulminant hepatic failure has been significantly

transformed by emergency orthotopic liver transplantation.

With this procedure, 1-year survival rates range from 55 to

80%. However, emergency liver transplantation still

encounters serious problems including patient selection, organ

availability, and the definition of optimum preoperative

management of these patients. Several surgical innovations

have been developed to resolve the shortage in liver grafts

such as liver graft reduction or splitting for transplantation in

two recipients. Because, spontaneous recovery remains

unpredictable, new techniques are proposed such as the

temporary orthotopic transplantation of auxiliary liver grafts,

xenografts with monkey or pigs livers, hepatic assistance and

bioartificial livers. These evolving strategies are currently

under evaluation. Preventive treatment is one of the most

effective approaches to fulminant hepatitis.

46. Eeg Olofsson, O.; Bergstrom, T.; Osterland, C. K.; Andermann, F.;

Olivier, A. Epilepsy etiology with special emphasis on immune

dysfunction and neurovirology. Brain-Dev. 1995; 17 Suppl: 58-

60; ISSN: 0387-7604.

NETHERLANDS. The etiology of epilepsy remains in most cases

an enigma. Based on the finding of a genetically dependent

immune dysfunction in focal epilepsies, brain specimens from

16 patients, ranging in age from 6 to 39 years and operated on

for therapy-resistant focal, mainly temporal lobe epilepsy

were analyzed for the presence of viral DNA. The PCR

technique was used for detection of viral DNA from the herpes

virus group. HSV-1 was found in 44% CMV in 50%, and HHV-6 in

25%. Three patients were positive for more than one of these

viruses. The control material, consisting of only 4 brain tissue

samples, showed DNA from HSV-1 in one case. Until more brain

samples from controls have been examined, caution must be

taken before a viral etiology is applied to focal epilepsy.. 0.

47. Elcuaz, R.; Bordes, A.; Aladro, Y.; Garcia, A.; Perera, A.; Valle, L.;

Canas, F.; Lafarga, B. [Clinical characteristics and

epidemiologic study of a listeriosis outbreak in Grand Canary].

Caracteristicas clinicas y estudio epidemiologico de un brote

de listeriosis en Gran Canaria. Enferm-Infecc-Microbiol-Clin.

1996 Aug; 14(7): 416-21; ISSN: 0213-005X.

SPAIN. BACKGROUND AND METHODS: Human infections caused

by Listeria monocytogenes often present as sporadic cases

without any epidemiological relationship among them; however

they also appear as outbreaks that are usually detected by an

increase in the number of cases diagnosed by hospitals of the

geographic area. Between December 1991 and May 1993,

twenty four cases of listeriosis were detected in three

hospitals of Las Palmas de Gran Canaria; and they were

classified as an outbreak. Our report describes its clinical,

epidemiological and microbiological aspects. RESULTS AND

CONCLUSIONS: Twenty four cases of listeriosis were

diagnosed, 12 occurred in pregnant women or neonates (5 and 7

respectively) and 12 in non pregnant adults. All adult

infections were community-acquired. The incidence rate was,

for the epidemic area, 76.3 cases per million population during

the period considered (18 months). Among non pregnant adults,

9/12 patients had some underlying disease and 9/12 presented

CNS affection (meningitis and/or cerebritis). In the group of

pregnant women, 4 cases occurred in the second trimester and

fetal loss was caused; one case was detected in the third

trimester and four weeks later the patient delivered an

unaffected infant. All cases of neonatal listeriosis presented

as early-onset sepsis. Of the 24 strains of L. monocytogenes,

21 were serotype 4, two were serotype 1 and one was not

typeable. Strains from 12 patients were available for

epidemiological analysis, seven of which corresponded to the

same pattern and there were three more different patterns.

48. Endo, K.; Sasaki, H.; Wakisaka, A.; Tanaka, H.; Saito, M.; Igarashi,

S.; Takiyama, Y.; Sanpei, K.; Iwabuchi, K.; Suzuki, Y.; Onari, K.;

Suzuki, T.; Weissenbach, J.; Weber, J. L.; Nomura, Y.; Segawa, M.;

Nishizawa, M.; Tsuji, S. Strong linkage disequilibrium and

haplotype analysis in Japanese pedigrees with Machado-Joseph

disease. Am-J-Med-Genet. 1996 Sep 20; 67(5): 437-44; ISSN:

0148-7299.

UNITED-STATES. To identify the markers tightly linked to

Machado-Joseph disease (MJD) and to investigate whether a

limited number of ancestral chromosomes are shared by

Japanese MJD pedigrees, a detailed linkage analysis employing

D14S55, D14S48, D14S67, D14S291, D14S280, AFM343vf1,

D14S81, D14S265, D14S62, and D14S65 was performed. The

results of multipoint linkage analysis as well as detection of

critical recombination events indicate that the gene for MJD is

localized in a 4-cM region between D14S280-D14S81. We

found strong linkage disequilibria at AFM343vf1 and D14S81,

and association of a few common haplotypes with MJD. These

results indicate that there is an obvious founder effect in

Japanese MJD and suggest the possibility of the existence of

predisposing haplotypes which are prone to expansions of CAG

repeats.. 0; 0; 0.

49. Ericsson, K.; Hilleras, P.; Holmen, K.; Winblad, B. Human-figure

drawing (HFD) in the screening of cognitive impairment in old

age. J-Med-Screen. 1996; 3(2): 105-9; ISSN: 0969-1413.

ENGLAND. OBJECTIVE: The aim of the study is to test the

hypothesis that freehand human-figure drawing (HFD), can be

used as a complementary screening instrument to

differentiate between demented elderly people and healthy

elderly controls in population based studies. METHOD: HFD was

examined in 668 elderly ( > or = 75 years of age) participants

from an epidemiological study in Stockholm, who were asked

to draw a human figure. The drawings were analysed on the

content of body details and structural characteristics. RESULT:

The results show quite clearly that the body details and the

height decrease with decreasing cognitive function, whereas

the centredness (the distance in cm from the centre of the

figure to the centre of the paper) increases with decreasing

cognitive functioning. Demented people place their figures in

the upper left corner of the sheet, compared with the mostly

well centred figures of non-demented people. Age, on the other

hand, has an influence on the HFD as after 90 years of age most

of the variables show regressive changes. CONCLUSION: The

HFD can help to differentiate between demented and non-

demented subjects as well as between dementia of different

severity. The HFD does not help us, however, to discriminate

between Alzheimer's disease and vascular dementia. Age has

an influence on the HFD in the sense that after 90 years most

of the variables regress to a smaller or more primitive form.

50. Esler, W. P.; Stimson, E. R.; Ghilardi, J. R.; Lu, Y. A.; Felix, A. M.;

Vinters, H. V.; Mantyh, P. W.; Lee, J. P.; Maggio, J. E. Point

substitution in the central hydrophobic cluster of a human

beta-amyloid congener disrupts peptide folding and abolishes

plaque competence. Biochemistry. 1996 Nov 5; 35(44): 13914-

21; ISSN: 0006-2960.

UNITED-STATES. Alzheimer's disease (AD) is pathologically

characterized by the presence of numerous insoluble amyloid

plaques in the brain composed primarily of a 40-43 amino acid

peptide, the human beta-amyloid peptide (A beta). The process

of A beta deposition can be modeled in vitro by deposition of

physiological concentrations of radiolabeled A beta onto

preexisting amyloid in preparations of unfixed AD cerebral

cortex. Using this model system, it has been shown that A beta

deposition is biochemically distinct from A beta aggregation

and occurs readily at physiological A beta concentrations, but

which regions and conformations of A beta are essential to A

beta deposition is poorly understood. We report here that an

active congener, A beta (10-35)-NH2, displays time

dependence, pH-activity profile, and kinetic order of

deposition similar to A beta (1-40), and is sufficiently soluble

for NMR spectroscopy in water under conditions where it

actively deposits. To examine the importance of the central

hydrophobic cluster of A beta (LVFFA, residues 17-21) for in

vitro A beta deposition, an A beta (10-35)-NH2 analog with a

single point substitution (F19T) in this region was synthesized

and examined. Unlike A beta (10-35)-NH2, the F19T analog was

plaque growth incompetent, and NMR analysis indicated that

the mutant peptide was significantly less folded than wild-

type A beta. These results support previous studies suggesting

that the plaque competence of A beta correlates with peptide

folding. Since compounds that alter A beta folding may reduce

amyloid deposition, the central hydrophobic cluster of A beta

will be a tempting target for structure-based drug design

when high-resolution structural information becomes

available.. 0; 0.

51. Exhenry, C.; Nadal, D. Vertical human immunodeficiency virus-1

infection: involvement of the central nervous system and

treatment. Eur-J-Pediatr. 1996 Oct; 155(10): 839-50; ISSN:

0340-6199.

GERMANY. Involvement of the central nervous system (CNS)

contributes substantially to morbidity and mortality of

vertical infection with the human immunodeficiency virus

(HIV)-1. The clinical spectrum ranges from minor

developmental disabilities to severe and progressive

encephalopathy. Progression of the disease varies

considerably. Both direct viral and indirect host-related

pathogenic mechanisms have been proposed. The diagnosis

depends on neurological and neurodevelopmental assessments.

So far, HIV-1-specific antiviral treatment has shown limited

effects on neurological manifestations in symptomatic

children. Thus, efforts are needed to improve prevention and

treatment of CNS involvement. It is still unclear whether early

use of antiretroviral agents is of benefit. CONCLUSION: Since

experience of treatment of HIV-1 infections in adults cannot

easily be translated to children, paediatric clinical trials are

needed to answer questions specific to the unique

characteristics of children.. 0.

52. Feucht, H. H.; Fischer, L.; Sterneck, M.; Broelsch, C. E.; Laufs, R. GB

virus C transmission by blood products [letter]. Lancet. 1997

Feb 8; 349(9049): 435; ISSN: 0140-6736.

ENGLAND.

53. Fleck, L. M. Just caring: the moral and economic costs of APOE

genotyping for Alzheimer's disease. Ann-N-Y-Acad-Sci. 1996

Dec 16; 802: 128-38; ISSN: 0077-8923.

UNITED-STATES. 0; 0.

54. Forss, N.; Merlet, I.; Vanni, S.; Hamalainen, M.; Mauguiere, F.; Hari,

R. Activation of human mesial cortex during somatosensory

target detection task. Brain-Res. 1996 Sep 23; 734(1-2): 229-

35; ISSN: 0006-8993.

NETHERLANDS. We recorded somatosensory evoked fields

(SEFs) from 10 healthy subjects to ulnar and median nerve

stimuli presented at random intervals of 2.4-21.6 s. The

subjects either counted the stimuli or ignored them by reading

a book. The stimuli activated in both conditions the

contralateral SI cortex, the ipsi- and contralateral SII

cortices, and the posterior parietal cortex (PPC), in line with

earlier observations. In addition, a novel response was

observed in nine subjects at 120-160 ms. It was clearly

enhanced by attention and was generated in the mesial cortex

of the paracentral lobule, close to the end of the central

sulcus.

55. Fujita, N.; Suzuki, K.; Vanier, M. T.; Popko, B.; Maeda, N.; Klein, A.;

Henseler, M.; Sandhoff, K.; Nakayasu, H.; Suzuki, K. Targeted

disruption of the mouse sphingolipid activator protein gene: a

complex phenotype, including severe leukodystrophy and wide-

spread storage of multiple sphingolipids. Hum-Mol-Genet. 1996

Jun; 5(6): 711-25; ISSN: 0964-6906.

ENGLAND. The four established or putative sphingolipid

activator proteins derive from a large precursor protein

encoded by a single gene. In addition to generating the four

sphingolipid activator proteins, the precursor protein is

suspected of having functions of its own, as, for example, a

lipid binding/transport protein or a neurotrophic factor. The

gene also appears to encode the Sertoli cell major sulfated

glycoprotein. Sequence similarities have been noted with many

other proteins of diverse functions. One patient and a fetus in

a single family with a complete defect of this gene due to a

mutation in the initiation codon exhibited complex

pathological and biochemical abnormalities. Mutant mice

homozygous for an inactivated gene of the sphingolipid

activator protein precursor exhibit two distinct clinical

phenotypes-neonatally fatal and later-onset. The latter

develop rapidly progressive neurological signs around 20 days

and die by 35-38 days. At 30 days, severe hypomyelination and

periodic acid-Schiff-positive materials throughout the

nervous system and in abnormal cells in the liver and spleen

are the main pathology. Most prominently lactosylceramide,

and additionally ceramide, glucosylceramide,

galactosylceramide, sulfatide, and globotriaosylceramide are

abnormally increased in the brain, liver, kidney, and their

catabolism abnormally slow in cultured fibroblasts. Brain

gangliosides are generally increased, particularly the

monosialogangliosides. The clinical, pathological and

biochemical phenotype closely resembles that of the human

disease. This model not only allows further clarification of

the physiological functions of the four individual sphingolipid

activator proteins but also should be useful to explore

putative functions of the precursor protein.. 0; 0; 0; 0.

56. Fukuyama, H.; Yamauchi, H. [Positron emission tomography and

single photon CT in the diagnosis of cerebrovascular

disorders]. Rinsho-Shinkeigaku. 1995 Dec; 35(12): 1578-80;

ISSN: 0009-918X.

JAPAN. The positron emission tomography (PET) and single

photon emission CT (SPECT) revealed the pathophysiology of

ischemic brain in the transaxial images. There are several

limitations in PET studies by continuous inhalation method

using oxygen-15 labeled gases. There has been a suspicion

about the constancy between the red cell volume and plasma

volume in the ischemic brain. We measured plasma volume by

PET using Cu-62 labeled human serum albumin in cases of

internal carotid artery occlusion. There was no remarkable

plasma volume alterations between the ischemic and non-

ischemic hemisphere. Powers et al demonstrated the

relationships between the intracranial perfusion pressure

changes and vascular or metabolic adaptations. The important

issue in acute stage of stroke is to differentiate the truly

alive and completely destroyed tissue. Cerebral blood flow

change might be affected during acute stage by diaschisis.

Recent examination using benzodiazepine receptor imaging by

SPECT might have a potential to depict the damaged tissues,

because cortical neuronal cell bodies have a lot of the

receptors and an ischemic insult induces the loss of the

receptors. The relationship of crossed cerebellar

hypoperfusion (CCH) and supratentorial circulatory conditions

is attractive, because supratentorial hypometabolism of

oxygen induced more severe CCH in internal carotid artery

occlusion. Therefore, we can predict the supratentorial oxygen

metabolism by CCH in a case of internal artery occlusion. We

have a lots of tools to explore the pathophysiological states of

ischemic brain. These must be dedicated to develop the more

effective therapeutic procedures.. 0.

57. Gatev, P.; Thomas, S.; Lou, J. S.; Lim, M.; Hallett, M. Effects of

diminished and conflicting sensory information on balance in

patients with cerebellar deficits. Mov-Disord. 1996 Nov; 11(6):

654-64; ISSN: 0885-3185.

UNITED-STATES. We studied the effects of altered sensory

information on standing balance in 25 patients with cortical

cerebellar atrophy (CCA), nine patients with olivoponto-

cerebellar atrophy (OPCA), and 10 normal subjects. The total

sway path and its components, the anteroposterior (AP) sway

path and the lateral sway path, were measured under six

conditions: (1) standing on a fixed platform with the eyes open

and visual surroundings fixed, (2) standing on a fixed platform

with the eyes closed, (3) standing on a fixed platform with the

eyes open and visual surroundings AP sway referenced, (4)

standing on an AP sway-referenced platform with the eyes

open and visual surroundings fixed, (5) standing on an AP

sway-referenced platform with the eyes closed, and (6)

standing on an AP sway-referenced platform with the eyes

open and visual surroundings AP sway referenced. Patients

swayed more than normal subjects during normal stance

(condition 1), when the visual information was absent

(condition 2) or distorted (condition 3), and when the

proprioceptive information from the ankles was distorted

(condition 4). Patients swayed much more than normal, and

most fell, when two sensory modalities were affected under

condition 5 (proprioceptive information distorted and visual

information absent) and condition 6 (both proprioceptive

information and visual information distorted). When the

patients' sway was normalized to that of the first condition,

however, only their lateral sway was greater than the sway in

normal subjects. Unlike in normal subjects, the patients'

lateral sway varied with the AP sway to approximately the

same degree in each condition for conditions 1-5. Clinical

ratings of gait and balance were highly correlated with the

sway measures. Quantitative testing of standing balance with

altered sensory information has better sensitivity than normal

stance testing.

58. Gentilini, P.; Laffi, G.; La Villa, G.; Casini Raggi, V.; Romanelli, R.

G.; Buzzelli, G.; Mazzanti, R.; Marra, F.; Pinzani, M.; Zignego, A. L.

[Viral liver cirrhosis: natural course, pathogenesis and clinical

implications of the complications]. La cirrosi epatica virus-

correlata: storia naturale, patogenesi e implicazioni cliniche

delle complicanze. Ann-Ital-Med-Int. 1996 Oct; 11 Suppl 2:

23S-29S; ISSN: 0393-9394.

ITALY. The role of hepatitis B virus (HBV) and hepatitis C

virus (HCV) as a major cause of chronic liver disease is now

accepted worldwide. This study was aimed at evaluating the

natural history of the disease in patients with virus-induced

chronic active hepatitis or cirrhosis, and the influence played

by age, sex and etiology, liver function tests and by the

occurrence of different complications. We retrospectively

examined the clinical records of 506 inpatients: 194 were

affected by chronic active hepatitis (125 males, 69 females,

mean age 45 +/- 11 years, 146 HCV- and 48 HBV-related), and

312 by cirrhosis without clinical evidence of portal

hypertension (178 males, 134 females, mean age 53 +/- 9

years, 249 HCV- and 63 HBV-related). The occurrence of

cirrhosis in the chronic active hepatitis group was then

calculated, together with the occurrence of complications and

the cumulative mortality rate of established cirrhosis. During

follow-up 93 patients with chronic hepatitis developed

cirrhosis. The cumulative probability of developing cirrhosis

in this group was 6.64% at 5 years, 56.1% at 10 years and

86.8% at 15 years. These patients were therefore included in

the cirrhosis group for the final analysis, so that a total of

405 cirrhotic patients were evaluated: these patients had a

cumulative survival rate of 99.1% at 5, 76.8% at 10 and 49.4%

at 15 years. Comparing the age-adjusted death rate of our

patients with the general Italian population, we observed that

in patients with liver cirrhosis it was 3.14 and 2.84 times

higher in men and women, respectively. Bilirubin was an

independent indicator of survival. Several complications, such

as esophageal varices, ascites, jaundice, hemorrhage, hepatic

encephalopathy and hepatocellular carcinoma significantly

reduced the survival rate and were indicated as major

complications, while thrombocytopenia, cholelithiasis and

diabetes did not affect survival and thus were called minor

complications. Incidence of hepatocellular carcinoma was very

high especially in males, without correlation with etiology. In

conclusion, the progression of virus-induced chronic active

hepatitis to cirrhosis is not influenced by sex and etiology.

Similarly, the different etiology does not modify the natural

history of cirrhosis while the occurrence of one or more major

complications significantly shortens survival. The longer

survival rate observed in patients with cirrhosis included in

this study is probably due to the selective inclusion of

patients with early disease and no evidence of portal

hypertension.

59. Gettler, J. F.; Garner, B. F. Long-term survival of an AIDS patient

with a tuberculous cerebral abscess. J-Natl-Med-Assoc. 1996

Sep; 88(9): 605-6; ISSN: 0027-9684.

UNITED-STATES. Unlike other forms of tuberculosis,

tuberculous cerebral abscess is a rare complication of human

immunodeficiency virus (HIV) infection and usually presents at

a late stage of the disease. This article describes a case of

tuberculous cerebral abscess in an HIV-infected patient that

was effectively treated with surgery and chemotherapy. The

patient has survived more than 5 1/2 years since being

diagnosed and remains in good health.. 0.

60. Gilissen, E.; Zilles, K. The calcarine sulcus as an estimate of the

total volume of human striate cortex: a morphometric study of

reliability and intersubject variability. J-Hirnforsch. 1996;

37(1): 57-66; ISSN: 0021-8359.

GERMANY. The human primary visual cortex consists of a

region buried in the calcarine sulcus and a region outside this

sulcus on the free surface of the occipital lobe. Since the

depth of the calcarine sulcus can be easily estimated in

magnetic resonance images of the living human brain, in vivo

morphometry of the human primary visual cortex would be

feasible for studying development, intersubject variability and

interhemispheric asymmetry if the sulcal depth or a

correlated measure such as the intracalcarine surface area

would be a precise and reliable estimate of the total volume of

the human primary visual cortex. The correlations between

total volume of the striate cortex and its intra- and extra-

calcarine surface areas were therefore tested in the present

observations. The total volume of the striate cortex and the

surface areas of its intra-and extracalcarine portions were

measured in Nissl-stained serial sections through 20 adult

human hemispheres. The intra- and extracalcarine portions of

the striate area are not significantly correlated with each

other, but correlated with the total volume of the striate

cortex. The intracalcarine surface area or the depth of the

calcarine sulcus are thus useful parameters for in vivo

estimates of the total size of the striate cortex.

61. Gitelman, D. R.; Alpert, N. M.; Kosslyn, S.; Daffner, K.; Scinto, L.;

Thompson, W.; Mesulam, M. M. Functional imaging of human

right hemispheric activation for exploratory movements. Ann-

Neurol. 1996 Feb; 39(2): 174-9; ISSN: 0364-5134.

UNITED-STATES. We employed positron emission tomography

to examine the functional anatomy of the exploratory-motor

aspect of spatial attention. Subjects moved their right hand

under nonexploratory (control) versus exploratory (active)

conditions. Movement architecture and eye movements were

matched across conditions. Statistical parametric maps of the

exploratory (active) minus nonexploratory (control) tasks in

subjects using their right hand in the right hemispace

demonstrated activation in right cingulate, premotor and

posterior parietal areas. The net activation of multiple right

hemisphere cortical areas ipsilateral to the active limb and

hemispace strongly supports the predicted, distributed

network anatomy and is consistent with possible right

hemispheric dominance for exploratory attentional movements.

62. Gotow, T.; Sakata, M.; Funakoshi, T.; Uchiyama, Y. Preferential

localization of annexin V to the axon terminal. Neuroscience.

1996 Nov; 75(2): 507-21; ISSN: 0306-4522.

UNITED-STATES. To examine the participation of annexin V, a

member of Ca(2+)-dependent phospholipid-binding proteins, in

the process of synaptic vesicle exocytosis, rat central nervous

tissue was analysed using biochemical and morphological

techniques. By both fluorescence and confocal laser scanning

microscopy, immunoreactivity for annexin V was

predominantly localized around neuronal somata and dendrites,

and the reactivity was mostly co-labeled with that for

synaptophysin. The annexin V immunoreactivity was also

detectable, but less intensely, in neuronal perikarya, glial

cells and endothelial cells. Both immunoblot and

immunoelectron microscopic analyses with intact tissues,

synaptosomes and purified synaptic vesicles showed that

annexin V was expressed in neurons, preferentially

concentrated in axon terminals and associated with synaptic

vesicles. Purified synaptic vesicles were relatively

homogeneously distributed in the medium where Ca2+ was

removed and thus the amount of annexin V was reduced

drastically. The vesicles tended to be clustered in the fraction

where endogenous annexin V is maintained, and the clusters

were more conspicuous when purified human annexin V was

added. Synaptic vesicles forming the clusters were not

directly fused with each other but separated by a 10-15 nm

gap that corresponded well with the size of single annexin V

molecules. In axon terminals, globular structures 12-13 nm in

diameter, similar in dimension to annexin V molecules, were

distinctly found to be attached to the cytoplasmic surface of

both vesicle membranes when the two vesicles were close to

each other. These results suggest that annexin V belongs to the

group of synaptic vesicle-associated proteins. Although its

localization and significance in non-neuronal cells were not

analysed here, at least in the axon terminal annexin V may

participate in the cluster formation of synaptic vesicles by

linking with the cytoplasmic surface of the vesicles in a

Ca(2+)-dependent manner.. 0.

63. Griffiths, P. D.; Crossman, A. R. Autoradiography of transferrin

receptors in the human brain. Neurosci-Lett. 1996 Jun 14;

211(1): 53-6; ISSN: 0304-3940.

IRELAND. Transferrin is the major protein concerned with iron

transport in the serum and may provide a route by which iron

enters the brain. This study was designed to show the optimal

binding conditions for in vitro transferrin receptor

autoradiography and to show the regional distribution of

transferrin receptors in the human brain. Optimal binding

conditions were: 120 min incubation with 5.0 nM 125I-

transferrin at 37 degrees C. Transferrin receptors degrade

quickly even with storage at -70 degrees C, therefore binding

studies should be performed within 7 days post mortem.

Transferrin receptors were widely distributed in the human

brain, with high density in the neocortex, moderate densities

in the putamen and caudate nuclei, and very low densities in

the globus pallidus and substantia nigra. Therefore transferrin

receptor density shows a mismatch with the known

distribution of iron in the human brain. The presence and

distribution of transferrin receptors in the human brain are

important because they may provide a route to deliver

lipophobic substances across the blood-brain barrier by

binding them to antibodies raised against transferrin

receptors.. 0; 0; 11096-37-0; 7439-89-6.

64. Grozdanovic, Z.; Gosztonyi, G.; Gossrau, R. Nitric oxide synthase I

(NOS-I) is deficient in the sarcolemma of striated muscle

fibers in patients with Duchenne muscular dystrophy,

suggesting an association with dystrophin. Acta-Histochem.

1996 Jan; 98(1): 61-9; ISSN: 0065-1281.

GERMANY. Previously, we have demonstrated the expression of

the brain-type nitric oxide synthase (NOS-I) in the

sarcolemmal region of somatic and visceral striated muscle

fibers in a variety of mammalian species through the use of

enzyme histochemical and immunochemical techniques. Here

we report that NOS-I protein and its NADPH diaphorase

(NADPHd) activity are co-localized in the sarcolemma of

human skeletal muscles. NOS-I immunolabeling and NADPHd

activity showed no significant variation between type I and II

fibers. In muscle biopsy specimens from patients with

Duchenne muscular dystrophy (DMD), both NOS-I protein and

activity were absent or markedly reduced. We, therefore,

propose that NOS-I is complexed with dystrophin and/or

dystrophin-associated proteins, adding a novel member to the

sarcolemmal dystrophin-glycoprotein complex (DGC). The

nature of the NOS-I-DGC link, and its role in skeletal muscle

physiology and pathophysiology remain to be elucidated.. EC

1.14.13.39; EC 1.6.99.1; 0.

65. Gudovic, R.; Milutinovic, B. Regression changes in inferior olivary

nucleus compared to changes of Purkinje cells during

development in humans. J-Hirnforsch. 1996; 37(1): 67-72;

ISSN: 0021-8359.

GERMANY. Human fetal brains were investigated in order to

establish the regressional process in two directly dependent

structures: in the inferior olivary nucleus and in cerebellar

Purkinje cells. Inferior olivary nucleus is the main origin of

the climbing fibres, that form one of two direct input systems

into the cerebellum. For the purpose 25 fetal human brains at

various stages of development (12.5, 15, 16.5 19.5 24, and 31

postovulatory week), together with one brain of newborn (in

further text: 41. postovulatory week) were used. Numerical

density of nuclei in both regions was determined by

stereological technique. In both structures appeared a

reduction in the number of nuclei, showing specific dynamics

during the intrauterine maturation. The data obtained were

analyzed by graphical and numerical method, that allowed the

formation of the adequate mathematical models for both

structures, that precisely described their regression changes.

The data presented indicate that the reduction is very

pronounced until the 18-19 postovulatory week, and after that

time it is remarkable slowed down. That period is therefore

the probable breakpoint of the appearance of synaptic contacts

between climbing fibres and Purkinje cell dendrites.

66. Guldberg, P.; Henriksen, K. F.; Sipila, I.; Guttler, F.; de, la Chapelle

A. Phenylketonuria in a low incidence population: molecular

characterisation of mutations in Finland. J-Med-Genet. 1995

Dec; 32(12): 976-8; ISSN: 0022-2593.

ENGLAND. The incidence of phenylketonuria (PKU) in Finland is

extremely low, probably below 1 in 100,000. We describe the

mutations and haplotypes in all four presently known patients.

Mutation R408W was found on four mutant chromosomes (all

haplotype 2), and IVS7nt1, R261Q, and IVS2nt1 were each

found on a single chromosome. No mutation was found on the

remaining chromosome. These findings support a pronounced

negative founder effect as the cause of the low incidence of

PKU in Finland, and are consistent with existing data regarding

the European and Baltic origin of Finnish genes.

67. Haass, C. Presenile because of presenilin: the presenilin genes and

early onset Alzheimer's disease. Curr-Opin-Neurol. 1996 Aug;

9(4): 254-9; ISSN: 1350-7540.

UNITED-STATES. Alzheimer's disease is a neurodegenerative

disorder characterized by the massive and invariant

accumulation of amyloid plaques in the brains of affected

patients. In many cases Alzheimer's disease occurs in the

absence of a prior history of the disease in other family

members and is designated as sporadic, whereas in

approximately 10% of patients, dominantly transmitted

mutations within one of three genes are found. A few

mutations have been identified within the gene encoding the

beta-amyloid precursor protein; however, these mutations

account for only about 1-3% of cases with familial

Alzheimer's disease. In the majority of autosomal dominant

cases (40-50%), mutations have been found in a gene localized

to chromosome 14. The responsible gene, now called

presenilin-1, has recently been identified and shown to encode

a putative seven transmembrane domain protein. Surprisingly,

a second highly homologous gene (named presenilin-2) was

cloned shortly thereafter. It is localized on human chromosome

1 and is also involved in a small number of cases with familial

Alzheimer's disease. Early data suggest that mutations found

within the two genes cause early onset Alzheimer's disease by

influencing the proteolytic processing of amyloid beta-peptide

in a pathological manner.. 0; 0; 0; 0.

68. Hand, P. A.; Inskip, A.; Gilford, J.; Alldersea, J.; Elexpuru

Camiruaga, J.; Hayes, J. D.; Jones, P. W.; Strange, R. C.; Fryer, A.

A. Allelism at the glutathione S-transferase GSTM3 locus:

interactions with GSTM1 and GSTT1 as risk factors for

astrocytoma. Carcinogenesis. 1996 Sep; 17(9): 1919-22; ISSN:

0143-3334.

ENGLAND. We describe studies to assess the influence of

polymorphism in the human glutathione S-transferase GSTM3

gene on susceptibility to high grade astrocytoma.

Immunohistochemical studies using a GSTM3-specific

antiserum identified expression of the GSTM3 subunit in

astrocytes. The relative levels of expression of GSTM1 and

GSTM3 in brain cytosols were determined after resolution of

these enzymes using chromatofocusing. We found no

differences in the level of GSTM3 activity in individuals with

GSTM1 null and those with GSTM1-positive genotypes (GSTM1

A, GSTM1 B and GSTM1 A/B). A case-control study was

performed to determine if GSTM3 alone or in combination with

GSTM1 or GSTT1 influenced susceptibility to high grade

astrocytoma. After correction for differences in age and

gender, GSTM3 AA was not significantly different in cases

compared with controls. No significant interactions between

GSTM3 AA and GSTM1 null were identified. The significant

interaction between GSTM3 AA and GSTT1 null appeared to

result from the strength of the main effect (GSTT1 null). The

data show that while GSTM3 is expressed in astrocytes and

contributes significantly to total GST activity in human brain,

it does not appear to influence susceptibility to high grade

astrocytoma. Further, unlike lung, there appears to be no

relationship between the level of GSTM3 activity in brain and

GSTM1 genotype.. EC 2.5.1.18; 0.

69. Haraldseth, O.; Jones, R. A.; Muller, T. B.; Fahlvik, A. K.; Oksendal,

A. N. Comparison of dysprosium DTPA BMA and

superparamagnetic iron oxide particles as susceptibility

contrast agents for perfusion imaging of regional cerebral

ischemia in the rat. J-Magn-Reson-Imaging. 1996 Sep; 6(5):

714-7; ISSN: 1053-1807.

UNITED-STATES. The aim of the study was to compare the

first-passage profiles of dysprosium diethylenetriamine

penta-acetic acid bis(methylamide) (DTPA BMA) and the

superparamagnetic iron oxide particles NSR 0430 in regions

with severe and moderate cerebral ischemia. In seven rats

subjected to middle cerebral artery occlusion, two dynamic MR

perfusion imaging series were acquired after intravenous

bolus injections of .5 mmol/kg dysprosium DTPA BMA and .06

mmolFe/kg iron oxide particles, respectively. The doses were

chosen to obtain similar maximum signal change in normally

perfused brain. The first-passage profiles were compared in a

region of interest (ROI) in the core area with severe ischemia

and in a ROI in the penumbra area of moderate ischemia. The

results were compared both as the calculated mean signal

intensity versus time curves for all seven rats and

statistically for an estimated mean transit time (MTT) after

gamma variate fitting of the calculated concentration versus

time curves. The first-passage profiles for the two contrast

agents were similar, both in the core area of severe ischemia

and in the penumbra area of moderate ischemia. In this rat

stroke model, dysprosium DTPA BMA and the

superparamagnetic iron oxide particles NSR 0430 were found

to be equally efficacious for the diagnosis of the perfusion

deficit, but if safe for human investigations, iron oxide

particles would have an advantage as equal susceptibility

effect may be achieved with smaller injection volumes.. 0; 0;

0; 128470-17-7; 1317-61-9; 67-43-6; 7429-91-6; 7439-89-

70. Harasty, J.; Halliday, G. M.; Kril, J. J. Reproducible sampling

regimen for specific cortical regions: application to speech-

associated areas. J-Neurosci-Methods. 1996 Jul; 67(1): 43-51;

ISSN: 0165-0270.

NETHERLANDS. The variability in the external gyri pattern of

human brains has made the identification of specific cortical

areas difficult. Studies correlating cortical structure and

function have not consistently controlled for this variability.

The aim of the present study was to develop a reliable and

reproducible regimen for sampling five speech-associated and

one non-speech associated cortical region in the human brain.

The gyri of interest were labelled using non-aqueous dye prior

to coronal slicing of brains at 3 mm intervals. Using the

labelled gyri, a set of internal brain landmarks was

established to aid in sampling one block of each cortical

region of interest. The position of each internal landmark was

determined as a percentage of the total brain length and

breadth. The variability in the position of each internal

landmark was investigated using analysis of variance and

found to be consistent in three dimensions in all cases. The

correlation of the sampled cortical region to the internal

landmark was consistent in different cases with point to point

agreement of 100%. This contrasts with the variability

between cases in external gyri features. The sampled region

was tested to determine cytoarchitectural variability by

measuring the depth of each cortical layer. This technique

found that the same cytoarchitectural regions were sampled in

each case. As expected, these regions were distinguishable by

the significant difference in the depth of different cortical

layers. Accurate identification of both the external gyri and

internal landmarks occurred with interrater point to point

agreement of 90-100%.

71. Harber, E. S.; O'Sullivan, M. G.; Jayo, M. J.; Carlson, C. S. Cerebral

infarction in two cynomolgus macaques (Macaca fascicularis)

with hypernatremia. Vet-Pathol. 1996 Jul; 33(4): 431-4; ISSN:

0300-9858.

UNITED-STATES. Hypernatremia resulting in neurologic

symptoms ranging from lethargy to coma, and with underlying

lesions of cerebral hemorrhage and thrombosis, has been

reported in human beings. Herein we report two cases of

cerebral infarction with venous thrombosis in cynomolgus

monkeys.Both animals were severely hypernatremic because of

water deprivation, with serum sodium levels of 185 and 193

meq/liter, respectively. At necropsy, there were bilateral

multiple hemorrhagic and malacic areas visible on the surface

of the cerebrum and extending into the parenchyma, primarily

involving the occipital lobes. These lesions were interpreted

microscopically as infarcts because, in addition to hemorrhage

and necrosis, multiple thrombi were present in small and

medium-sized veins of gray matter and meninges. The

pathogenesis of hypernatremia-induced cerebral lesions is

believed to involve cellular dehydration that caused shrinkage

of the brain. Because the vasculature of the brain is tightly

adherent to the skull, this shrinkage results in tearing of blood

vessels, with consequent hemorrhage and thrombosis.

72. Hendler, T.; Squires, N. K.; Moore, J. K.; Coyle, P. K. Auditory evoked

potentials in multiple sclerosis: correlation with magnetic

resonance imaging. J-Basic-Clin-Physiol-Pharmacol. 1996;

7(3): 245-78; ISSN: 0334-1534.

ENGLAND. The present study addresses issues regarding the

location of neural sources (i.e. generators) of human auditory

evoked potentials (AEPs), and the pattern of neural conduction

in the auditory pathway. AEPs were recorded from fifteen

patients with multiple sclerosis (MS) and compared to

normals. The recordings included auditory brainstem responses

(ABRs), mid-latency responses (MLRs), and long-latency

responses (LLRs). AEP latency abnormalities were related to

the locus of demyelinating lesions, as determined by magnetic

resonance imaging (MRI) scans. The data demonstrated several

anatomical patterns relating abnormal ABR wave intervals and

abnormal MRI signals. From these patterns specific loci for

ABR neural sources in the brainstem might be postulated. In

addition, the earlier the ABR waves, the more unilateral the

abnormalities appeared, suggesting bilateral sources for later

waves. The MLRs were highly correlated with ABR wave V and

were associated with greater abnormality in MRI signals in

midbrain and forebrain regions. In general, patients with

abnormal LLRs also had widespread AEP and MRI abnormalities,

supporting a multiple source approach for the N1 wave of the

LLRs. The observation that LLRs were only abnormal in the

presence of bilateral ABR abnormalities suggests a cross

wiring which would serve as a compensatory mechanism for

unilateral disturbances. The AEP data showed dissociation

between early and late wave abnormalities, thus supporting

parallel channels for neural conduction in the central auditory

system. Such a model calls for some degree of independence of

AEP generators along the auditory pathway.

73. Hinrichsen, S. L.; Moura, L. V.; Ataide Junior, L.; Travassos, F.;

Travassos, P.; Albuquerque, E.; Sepulveda, D. P.; Amorim, M. R.;

Luz, L. M.; Braga, A. A.; Rocha, L. V. [Cerebral malaria and AIDS:

case report]. Malaria cerebral e AIDS relato de caso. Arq-

Neuropsiquiatr. 1996 Jun; 54(2): 324-7; ISSN: 0004-282X.

BRAZIL. Although it has not been definitely proven that the

severity of malaria is associated to human immunodeficiency

virus (HIV) we know that infection through Plasmodium

falciparum can favor a rapid evolution of the HIV infection.

Besides, association of malaria with HIV/AIDS from a clinical

point of view can be clinically severe in the face of the

occurrence of other microorganisms or neoplasias, which

worsens the evolution and prognosis of the affected patients.

The concurrence of HIV with Plasmodium in malaria endemic

zones is a possibility which should always be taken into

consideration, since transmission is related to risk factors

caused by people's behavior which are not always promptly

revealed and/or identified. The authors report one case of

brain malaria infection by Plasmodium vivax and Plasmodium

falciparum in a patient with AIDS. They describe the clinical

evolution and therapy.

74. Hocking, B.; Gordon, I. R.; Grain, H. L.; Hatfield, G. E. Cancer

incidence and mortality and proximity to TV towers [see

comments]. Med-J-Aust. 1996 Dec 2; 165(11-12): 601-5; ISSN:

0025-729X.

Note: Comment in: Med J Aust 1996 Dec 2-16;165(11-12):599-

600.

AUSTRALIA. OBJECTIVE: To determine whether there is an

increased cancer incidence and mortality in populations

exposed to radiofrequency radiations from TV towers. DESIGN:

An ecological study comparing cancer incidence and mortality,

1972-1990, in nine municipalities, three of which surround

the TV towers and six of which are further away from the

towers. (TV radiofrequency radiation decreases with the

square of the distance from the source.) Cancer incidence and

mortality data were obtained from the then Commonwealth

Department of Human Services and Health. Data on frequency,

power, and period of broadcasting for the three TV towers

were obtained from the Commonwealth Department of

Communications and the Arts. The calculated power density of

the radiofrequency radiation in the exposed area ranged from

8.0 microW/cm2 near the towers to 0.2 microW/cm2 at a

radius of 4km and 0.02 microW/cm2 at 12 km. SETTING:

Northern Sydney, where three TV towers have been

broadcasting since 1956. OUTCOME MEASURES: Rate ratios for

leukaemia and brain tumour incidence and mortality,

comparing the inner with the outer areas. RESULTS: For all

ages, the rate ratio for total leukaemia incidence was 1.24

(95% confidence interval [CI], 1.09-1.40). Among children, the

rate ratio for leukaemia incidence was 1.58 (95% CI, 1.07-

2.34) and for mortality it was 2.32 (95% CI, 1.35-4.01). The

rate ratio for childhood lymphatic leukaemia (the most

common type) was 1.55 (95% CI, 1.00-2.41) for incidence and

2.74 (95% CI, 1.42-5.27) for mortality. Brain cancer incidence

and mortality were not increased. CONCLUSION: We found an

association between increased childhood leukaemia incidence

and mortality and proximity to TV towers.

75. Holt, D. J.; Hersh, L. B.; Saper, C. B. Cholinergic innervation in the

human striatum: a three-compartment model. Neuroscience.

1996 Sep; 74(1): 67-87; ISSN: 0306-4522.

UNITED-STATES. The mammalian striatum is divided into

compartments that are anatomically and neurochemically

distinct. The dorsal striatum has been described as containing

two compartments, striosomes and matrix, while the ventral

striatum is thought to have a more complex, multi-

compartmental organization. In this study, we sought to

characterize the compartmentalization of the dorsal and

ventral portions of the human striatum using choline

acetyltransferase as a marker. Image analysis was used to

assess relative densities of immunostaining, and three

distinct, choline acetyltransferase-immunostained

compartments were demonstrated: intensely immunostained,

moderately immunostained and weakly immunostained areas.

The dorsomedial portion of the striatum was made up of

moderately immunostained regions embedded within a densely

immunostained background, thus manifesting the

characteristic striosome/ matrix organization of the dorsal

striatum. However, the ventral and lateral two-thirds of the

striatum were made up of a mixture of densely immunostained,

moderately immunostained and weakly immunostained areas,

with the moderately immunostained region forming the bulk of

the background tissue, and smaller, densely immunostained and

weakly immunostained regions embedded within it. These

compartments were compared to regions defined by distinct

levels of acetylcholinesterase immunostaining in adjacent

sections; the staining patterns produced by the two

cholinergic markers were found to be identical except in some

portions of the nucleus accumbens, where

acetylcholinesterase immunostaining was found to be more

intense than choline acetyltransferase immunostaining. The

immunoreactive somata were mapped within sections stained

for choline acetyltransferase taken from different

rostrocaudal levels of the striatum, and the distributions and

densities of immunoreactive somata within these three

cholinergic compartments were determined. In general, the

densities of cholinergic somata roughly correlated with

immunostaining intensity of regions, e.g. the most intensely

immunostained compartment also had the highest densities of

cholinergic somata. However, in the rostroventral striatum,

the densities of cholinergic somata in the weakly

immunostained compartment roughly equalled the densities of

cholinergic somata in the moderately immunostained

compartment, suggesting that local axonal arborizations of

cholinergic cells may differ in density or orientation between

the two compartments, or, alternatively, that some of the

cholinergic cells in the weakly immunostained compartment

may project outside of the striatum. The large proportion of

striatum displaying ventral striatal characteristics (a

complex, multi-compart-mental organization) in humans

relative to that observed in other mammals suggests that the

role of the ventral striatum may be expanded and more highly

differentiated in the human brain.

76. Ikura, Y.; Sasaki, M.; Ohgami, M.; Ikebe, T.; Gotoh, K.; Bettoh, H.;

Sakurai, M. Mixed germ-cell tumor of the brain. Pathologic

study of six autopsy cases. Pathol-Res-Pract. 1996 Jun;

192(6): 595-603; ISSN: 0344-0338.

GERMANY. Intracranial mixed germ-cell tumors are rare. We

describe the findings from six autopsies of patients with

these tumors. The patients were all young at presentation

(mean age, 16 years), and five of the six were male. Headache,

vomiting, polyuria and diplopia were common symptoms.

Radiographic evaluation demonstrated a mass on the midline of

the brain. The patients were treated mainly with radiation, but

survival (mean, 3.7 years) was not as long as predicted. At

autopsy, the tumors occupied most of the ventricular spaces,

and ranged from being well-circumscribed to invasive. All

tumors contained both germinoma components and

nongerminomatous germ-cell tumor components. Because the

distribution of these components was not homogenous, at least

two sections were necessary for the diagnosis.

Immunoreactivity for placental alkaline phosphatase was

found in all tumors. Immunostaining for human chorional

gonadotropin, alpha-fetoprotein and carcinoembryonic antigen

was usually associated with abnormally high serum levels of

these tumors markers in life. A number of the cells in both

kinds of tumor components expressed proliferating cell

nuclear antigen, probably reflecting the intense malignant

potential.

77. Ito, H.; Kawashima, R.; Awata, S.; Ono, S.; Sato, K.; Goto, R.;

Koyama, M.; Sato, M.; Fukuda, H. Hypoperfusion in the limbic

system and prefrontal cortex in depression: SPECT with

anatomic standardization technique. J-Nucl-Med. 1996 Mar;

37(3): 410-4; ISSN: 0161-5505.

UNITED-STATES. Depression is a common psychiatric illness,

and several reports have described cerebral blood flow (CBF)

abnormalities on SPECT studies in affected patients. However,

because region of interest analyses were used to determine

significant CBF changes in these studies, there were

methodological limitations. Therefore, we investigated CBF

distribution abnormalities in depression on a pixel-by-pixel

basis using SPECT and an anatomic standardization technique

that has been commonly used for PET activation studies.

METHODS: Eleven patients with unipolar depression, six

patients with bipolar depression and nine age-matched normal

control subjects underwent HMPAO brain SPECT studies. The

radioactivities of SPECT images for each subject were

globally normalized to 100 counts/pixel. Then, each SPECT

image was transformed for standard brain anatomy using a

computerized Human Brain Atlas system. For each group, the

mean and variance images were calculated from the

standardized anatomic SPECT images, and group comparisons

were performed on a pixel-by-pixel basis. RESULTS:

Significant decreases in CBF in the prefrontal cortices, limbic

systems and paralimbic areas were observed in both

depression groups compared with the normal control group.

CONCLUSION: Decreases in CBF in these regions may be related

to impaired attention as well as cognitive and emotional

responses, which have been recognized as usual symptoms in

depression. The anatomic standardization technique promises

to be useful for group comparison analysis of brain SPECT on a

pixel-by-pixel basis for individual neurological and

psychiatric diseases.. 0; 0; 0.

78. Itoh, T.; Nishimura, R.; Matsunaga, S.; Kadosawa, T.; Mochizuki, M.;

Sasaki, N. Syringomyelia and hydrocephalus in a dog. J-Am-

Vet-Med-Assoc. 1996 Sep 1; 209(5): 934-6; ISSN: 0003-1488.

UNITED-STATES. A 7-year-old spayed female Pomeranian with

a 6-month history of progressive paraparesis was determined

to have syringomyelia accompanied with hydrocephalus.

Magnetic resonance imaging clearly revealed severe

syringomyelia in the cervical portion of the spinal cord, which

was directly connected to the marked dilated fourth ventricle.

Acetazolamide was prescribed for 3 weeks, but the neurologic

deficits progressed. Laminectomy of the first and second

vertebrae, which is one method of treating this type of

syringomyelia in human beings, was performed, and then,

acetazolamide was continued. The dog had partial

amelioration, and further deterioration was not evident in the

12 months after surgery.

79. Iuliano, L.; Signore, A.; Vallabajosula, S.; Colavita, A. R.;

Camastra, C.; Ronga, G.; Alessandri, C.; Sbarigia, E.; Fiorani, P.;

Violi, F. Preparation and biodistribution of 99m technetium

labelled oxidized LDL in man. Atherosclerosis. 1996 Sep 27;

126(1): 131-41; ISSN: 0021-9150.

IRELAND. Radiolabelled autologous low density lipoprotein

(LDL) has previously been used to study in vivo distribution and

metabolism of native-LDL. Non-invasive imaging of

atherosclerotic lesions using 99mTc-LDL was shown to be

feasible in animal models and patients but the clinical utility

remains to be assessed. Since recent reports suggest that

oxidized LDL may play a major role in the pathogenesis of

atherosclerosis, we developed a technique to oxidize

autologous LDL and compared the biodistribution of oxidized-

LDL with that of native-LDL in man. In addition, we evaluated

the uptake in vivo of oxidized- and native-LDL by

atherosclerotic plaques. LDL, obtained from human plasma was

treated with various combinations of copper ions and H2O2 to

induce oxidative modification by increasing the content of

lipid peroxidation products and electrophoretic mobility. When

LDL (0.3 mg/ml) was incubated with 100 microM Cu2+ and 500

microM H2O2 oxidation occurred rapidly within 1 h, and was

labelled with 99mTc efficiently as native LDL. In vivo

distribution studies revealed a faster plasma clearance of

oxidized-LDL compared to native-LDL, and a higher uptake by

the reticuloendothelial system. Tomographic scintigraphy of

the neck in patients suffering from transient ischemic

attacks, revealed accumulation of radiolabelled LDL

preparations in the carotid artery affected by atherosclerotic

lesions. We developed a technique to rapidly oxidize LDL using

copper and H2O2. Biodistribution data demonstrate that

oxidized-LDL is rapidly cleared from circulation, is taken up

mostly by organs rich in macrophages, and can be detected at

the level of carotid plaques.. 0; 0; 7440-26-8; 7722-84-1;

7758-98-7.

80. Jackson, S. R.; Husain, M. Visuomotor functions of the lateral pre-

motor cortex. Curr-Opin-Neurobiol. 1996 Dec; 6(6): 788-95;

ISSN: 0959-4388.

ENGLAND. Recent studies have provided new insights into the

visuomotor functions of the dorsal and ventral regions of the

lateral pre-motor cortex. Anatomical and physiological

investigations in non-human primates have demonstrated that

these regions have differing patterns of cortical connectivity

and distinctive neuronal responses. Brain-imaging techniques

and lesion studies have begun to probe the functions of

homologous regions in humans.

81. Jain, S.; Padma, M. V.; Puri, A.; Jyoti; Maheshwari, M. C. Occurrence

of epilepsies in family members of Indian probands with

different epileptic syndromes. Epilepsia. 1997 Feb; 38(2): 237-

44; ISSN: 0013-9580.

UNITED-STATES. PURPOSE: Large numbers of families with

many members having seizures have been used to understand

the role of hereditary factors in the pathogenesis of human

epileptic syndromes. We aimed to establish a genetic database

to form a hypothesis on the possible genetic contributions in

different epileptic syndromes. METHODS: The occurrence and

patterns of different epilepsies and epileptic syndromes in

1,219 Indian probands and their relatives were studied. The

concordance of epilepsies between probands and relatives was

also analyzed. RESULTS: Of probands, 231 (19% of 1219) had

first- or second-degree relatives affected with seizures.

Incidence of family history in probands with generalized

epilepsies (GES) and syndrome of single, small, enhancing

lesions (SSEL) was comparable and significantly higher than

that in probands with localization-related epilepsies (LRES).

The ratio of affected first- to second-degree relatives was

close to 4:1. Generalized epilepsies were the commonest type

of epileptic syndromes seen among all relatives. The

proportion of sibs and second-degree relatives with epileptic

syndromes similar to probands was significantly greater in

the GES group as compared with the concordant relatives of

probands with LRES and SSEL. CONCLUSIONS: A significant

percentage of first- and second-degree relatives of probands

with all types of epileptic syndromes have seizures. The risk

of relatives being affected varied as a function of the relation

with the proband. Concordance of epileptic syndromes between

probands and relatives was related to the epileptic syndromes

in probands. The syndrome of SSEL is probably a benign

epileptic syndrome seen in Indians genetically predisposed to

seizures. Hereditary factors may play an almost equal role in

the predisposition of relatives to epilepsy in families of

probands with different epileptic syndromes.

82. Jalan, R.; Seery, J. P.; Taylor Robinson, S. D. Review article:

pathogenesis and treatment of chronic hepatic encephalopathy.

Aliment-Pharmacol-Ther. 1996 Oct; 10(5): 681-97; ISSN:

0269-2813.

ENGLAND. The various treatment strategies for hepatic

encephalopathy are compared in the light of the available body

of scientific work on the pathogenesis of the syndrome. Data

on animal models of hepatic encephalopathy and in vitro

studies on brain slices are discussed. Difficulties in

extrapolating the results obtained to the human situation are

highlighted, while results of human positron emission

tomography and magnetic resonance spectroscopy studies are

outlined on the background of the potential weaknesses of

these non-invasive techniques.. 0; 0; 0; 0; 0; 0; 3230-94-2.

83. Jarvela, I.; Mitchison, H. M.; Munroe, P. B.; O'Rawe, A. M.; Mole, S. E.;

Syvanen, A. C. Rapid diagnostic test for the major mutation

underlying Batten disease. J-Med-Genet. 1996 Dec; 33(12):

1041-2; ISSN: 0022-2593.

ENGLAND. Batten disease is the most common progressive

neurodegenerative disorder of childhood in western countries.

A novel cDNA responsible for Batten disease has recently been

identified. We have developed a rapid diagnostic solid phase

minisequencing test to detect the major 1.02 kb deletion

which is responsible for 81% of affected chromosomes in

Batten disease worldwide. In Finland, 90% of Batten

chromosomes carry the major deletion owing to the

enrichment of the CLN3 gene in the isolated Finnish population.

84. Jarvik, J. G.; Lenkinski, R. E.; Saykin, A. J.; Jaans, A.; Frank, I.

Proton spectroscopy in asymptomatic HIV-infected adults:

initial results in a prospective cohort study. J-Acquir-

Immune-Defic-Syndr-Hum-Retrovirol. 1996 Nov 1; 13(3): 247-

53; ISSN: 1077-9450.

UNITED-STATES. The purpose of our study was to determine

whether proton magnetic resonance spectroscopy (MRS) could

detect early brain involvement by human immunodeficiency

virus (HIV). We recruited 19 asymptomatic HIV-infected

patients, 9 with and 10 without a history of intravenous drug

use (IDU), as well as 10 control subjects. All subjects had to

have normal MR imaging to be enrolled. We identified the

following peaks on proton MRS: n-acetyl aspartate, creatine,

choline, and a conglomerate amino acid peak between 2.1 and

2.6 parts per million that we call the marker peaks. Proton

MRS was able to demonstrate a statistically significant

difference between HIV-infected subjects and controls. The

marker/Cr was the best ratio to separate patients from

controls, with controls having a mean ratio of 0.50 +/- 0.51

and patients having a mean ratio of 1.8 +/- 0.85 (p = 0.001).

There was no difference between HIV-infected subjects with

and without a history of IDU. No significant relationship was

found between either neuropsychological test scores or CD4

count and metabolite ratios. In brief, MRS seems more

sensitive than magnetic resonance imaging (MRI), being able to

detect abnormalities in HIV-infected patients when imaging is

normal.. 0; 57-00-1; 62-49-7.

85. Jay, V.; Becker, L. E.; Blaser, S.; Hwang, P.; Hoffman, H. J.;

Humphreys, R.; Zielenska, M. Pathology of chronic herpes

infection associated with seizure disorder: a report of two

cases with tissue detection of herpes simplex virus 1 by the

polymerase chain reaction. Pediatr-Pathol-Lab-Med. 1995 Jan;

15(1): 131-46; ISSN: 1077-1042.

UNITED-STATES. Although uncommon, the association of

chronic encephalitis with epilepsy is well recognized. While a

viral etiology has been suspected based on the morphology, to

date no virus has been successfully cultured from the brain in

patients with Rasmussen's encephalitis. We describe the

pathologic findings and report the detection of herpes simplex

virus 1 (HSV1) in the brain in two patients who presented

primarily with intractable seizures. In the first patient, an

intrauterine infection was suspected as the underlying basis

for the seizure disorder and the extensive cerebral

calcification and gliosis. The second patient (with presumed

HSV1 encephalitis at age 7 months) underwent a temporal

lobectomy for medically refractory seizures at the age of 3

years and pathologic examination revealed a chronic

encephalitis. While immunohistochemical, ultrastructural, and

culture studies were negative for viral pathogens, molecular

analysis by the polymerase chain reaction (PCR) revealed HSV1

DNA sequences in both cases. Thus our cases represent two

examples of chronic encephalitis associated with a seizure

disorder, where a definitive viral etiology was documented by

PCR.. 0.

86. Ji, B. T.; Shu, X. O.; Linet, M. S.; Zheng, W.; Wacholder, S.; Gao, Y. T.;

Ying, D. M.; Jin, F. Paternal cigarette smoking and the risk of

childhood cancer among offspring of nonsmoking mothers. J-

Natl-Cancer-Inst. 1997 Feb 5; 89(3): 238-44; ISSN: 0027-

8874.

UNITED-STATES. BACKGROUND: Cigarette smoking has been

shown to increase oxidative DNA damage in human sperm cells.

Assessment of the role of cigarette smoking in the etiology of

childhood cancer has focused primarily on the effect of

maternal smoking. Similar studies in relation to paternal

smoking, however, have been inconclusive. Few studies have

evaluated the effect of paternal smoking in the preconception

period, and most of these could not disentangle the effects of

paternal from maternal smoking. PURPOSE: We investigated the

relationship of paternal smoking, particularly in the

preconception period, with childhood cancer among offspring

of the nonsmoking mothers. METHODS: We conducted a

population-based, case-control study in Shanghai, People's

Republic of China, where the prevalence of smoking is high

among men but extremely low among women. The study

included 642 childhood cancer case patients (<15 years of age)

and their individually matched control subjects. Information

concerning parental smoking, alcohol drinking, and other

exposures of the index child was obtained by direct interview

of both parents of the study subjects. Odds ratios (ORs),

derived from conditional logistic regression models, were

used to measure the association between paternal smoking and

risk of childhood cancers. RESULTS AND CONCLUSIONS: Paternal

preconception smoking was related to a significantly elevated

risk of childhood cancers, particularly acute leukemia and

lymphoma. The risks rose with increasing pack-years of

paternal preconception smoking for acute lymphocytic

leukemia (ALL) (P for trend = .01), lymphoma (P for trend =

.07), and total cancer (P for trend = .006). Compared with

children whose fathers had never smoked cigarettes, children

whose fathers smoked more than five pack-years prior to their

conception had adjusted ORs of 3.8 (95% confidence interval

[CI] = 1.3-12.3) for ALL, 4.5 (95% CI = 1.2-16.8) for lymphoma,

2.7 (95% CI = 0.8-9.9) for brain tumors, and 1.7 (95% CI = 1.2-

2.5) for all cancers combined. Statistically significant

increased risks of cancer were restricted to children under the

age of 5 years at diagnosis or those whose fathers had smoked

during all of the 5 years prior to conception. IMPLICATIONS:

Further studies are needed to confirm the association of

paternal smoking with increased risk of cancer in offspring, to

clarify the pattern of risks in relation to the timing of

cigarette smoking, and to elucidate the biologic mechanism

involved in predisposing the offspring to cancer. For example,

it may be that paternal smoking induces prezygotic genetic

damage that, in turn, acts as the predisposing factor.

87. Kapur, N.; Ellison, D.; Parkin, A. J.; Hunkin, N. M.; Burrows, E.;

Sampson, S. A.; Morrison, E. A. Bilateral temporal lobe

pathology with sparing of medial temporal lobe structures:

lesion profile and pattern of memory disorder.

Neuropsychologia. 1994 Jan; 32(1): 23-38; ISSN: 0028-3932.

ENGLAND. The lesion sustained by the amnesic patient H.M.

consisted of bilateral ablation of medial temporal lobe

structures with relative sparing of more lateral white matter

and neocortical structures. We present the first detailed

report of a case where the reverse pattern of lesions

predominated, namely bilateral pathology of white matter and

neocortical temporal lobe structures, with spared medial

temporal lobe structures. This damage, which was particularly

severe in anterior loci in the temporal lobes, was sustained as

a result of radionecrosis. High-resolution magnetic resonance

imaging was carried out to document the distinctive

anatomical profile of our patient, and this profile was

compared to that reported for the patient H.M. At the

anatomical level, there was an almost "mirror image" profile,

with contrasting involvement of lateral and medial temporal

lobe structures. At the neuropsychological level, our patient

was not amnesic but showed patchy impairment on traditional

tests of anterograde memory functioning, in the context of

notable "semantic" memory loss for knowledge acquired before

and after the onset of his illness. Our findings demonstrate

that bilateral temporal lobe pathology by itself does not lead

to a classical amnesic syndrome, but may result in a

significant but more subtle "semantic" memory loss. Our data

highlight the distinctive and dissociable contribution of

lateral and medial temporal lobe structures to human memory

processing, and suggest a major role for anterior-inferior

neocortical temporal lobe mechanisms in aspects of knowledge

acquisition, storage and retrieval.

88. Kawakami, H.; Maruyama, H.; Nakamura, S. [Molecular genetics of

Machado-Joseph disease]. Nippon-Rinsho. 1996 Mar; 54(3):

854-60; ISSN: 0047-1852.

JAPAN. Machado-Joseph disease (MJD) is an autosomal

dominant spinocerebellar degeneration. The CAG expansions of

the MJD1 gene at chromosome 14q32.1 was identified as the

cause of the disease. MJD has three factors that influence the

age of the onset. The MJD1 repeat length inversely correlated

with the age of onset (r = -0.87). Homozygosity of the gene

exhibited an additive effect on age of onset. MJD has a gender-

specific effect on the age of onset. A parent-child analysis

showed the unidirectional expansion of CAG repeats. Among

the three clinical subtypes, type I of MJD, with dystonia,

showed a larger degree of expansion in CAG repeats of the gene

and younger ages of onset than the other types.

89. Keita, M.; Bouteille, B.; Enanga, B.; Vallat, J. M.; Dumas, M.

Trypanosoma brucei brucei: a long-term model of human

African trypanosomiasis in mice, meningo-encephalitis,

astrocytosis, and neurological disorders. Exp-Parasitol. 1997

Feb; 85(2): 183-92; ISSN: 0014-4894.

UNITED-STATES. The search for a chronic experimental model

for human African trypanosomiasis (HAT) in animals with

cerebral lesions and neurological disorders has been difficult.

Models with meningo-encephalitis have been proposed using

Trypanosoma brucei gambiense or T. b. rhodesiense. Meningo-

encephalitis is rare in infection with T. b. brucei. It has been

shown that the treatment of mice infected with T. b. brucei

with diminazene aceturate (Berenyl) led to development of a

rapid meningo-encephalitis. In this study, we report the

development of a chronic experimental model of HAT in mice

infected with T. b. brucei AnTat 1.1E. To obtain a chronic

evolution of the infection, on Day 21 postinfection, mice were

treated with a dose of suramin (Moranyl) at 20 mg x kg(-1)

body weight, a dose which failed to eliminate trypanosomes in

the central nervous system (CNS). This treatment, repeated

after each parasitemic relapse in the blood, allowed animals

to survive more than 300 days postinfection. After a few

weeks of infection, mice displayed neurological signs.

Histological studies showed the appearance of increasing

inflammatory lesions, from meningitis to meningo-

encephalitis, with progression of lesions throughout the

perivascular spaces in cerebral and cerebellum parenchyma. No

demyelination or neuronal alteration were observed except in

the necrotic spaces. Trypanosomes were observed in different

structures in CNS. An immunohistochemical study of glial

fibrillary acidic protein (GFAP) showed an increasing

astrocytosis according to the duration of the infection. This

model reproduces neurological and histological pathology

observed in the human disease and can be useful for further

immunopathological, neurohistological and therapeutic studies

on this condition.. 0; 145-63-1.

90. Kenyon, L. C.; Dulaney, E.; Montone, K. T.; Goldberg, H. I.; Liu, G. T.;

Lavi, E. Varicella-zoster ventriculo-encephalitis and spinal

cord infarction in a patient with AIDS. Acta-Neuropathol-Berl.

1996 Aug; 92(2): 202-5; ISSN: 0001-6322.

GERMANY. Varicella-zoster virus (VZV) infection is usually

benign and self-limited. However, particularly in the

immunosuppressed host, serious central nervous system

complications may occur, including encephalitis, myelitis, and

cerebral vascular occlusion. We report the case of a 57-year-

old male with AIDS, who rapidly developed a sixth cranial

nerve palsy and progressive myelopathy. There was no

antecedent zoster rash. Autopsy revealed VZV ventriculo-

encephalitis and vasculitis, as well as a transverse infarction

of the spinal cord without evidence of direct infection of the

cord parenchyma. Spinal cord infarction secondary to VZV

vasculitis is an unusual cause of myelopathy in

immunosuppressed patients.

91. Kjeldsen, M. J.; Sorensen, T. T.; Friis, M. L. [Genetic aspects of

epilepsy]. Genetiske aspekter ved epilepsi. Nord-Med. 1996

Oct; 111(8): 275-8; ISSN: 0029-1420.

SWEDEN. Accumulating evidence suggests a significant

proportion of the forms of epilepsy to be genetically

determined. Several epilepsy syndromes have been mapped on

the human genome, though their molecular basis remains

unknown. Technical advances in molecular biology now provide

a basis for improving our understanding of the molecular

mechanisms involved in genetically determined types of

epilepsy Genetic mapping will improve the accuracy of genetic

counselling. Improved insight into the molecular biology may

help to elucidate the underlying epileptogenic mechanisms and

pave the way for new developments in pharmacological control

of epileptic seizures. Further advances in research on genetics

and epilepsy will require national and international

cooperation between epileptologists and geneticists in search

of informative families for linkage analysis.. 9007-49-2.

92. Kreuz, F. R. Attitudes of German persons at risk for Huntington's

disease toward predictive and prenatal testing. Genet-Couns.

1996; 7(4): 303-11; ISSN: 1015-8146.

SWITZERLAND. Huntington's disease is an autosomal dominant

neurodegenerative disorder characterized by involuntary

movements, psychological deterioration and dementia. Indirect

predictive testing by linkage analysis has been possible since

1983; direct predictive testing by detecting the instable CAG-

repeat has been possible since 1993. Persons at risk were

asked, by questionnaire, about their motivation and regarding

attitude taking part in indirect and direct predictive and

prenatal diagnostics. About half of the interrogated German

persons at risk wish to undertake DNA analysis, whereas 32.7%

do not want to take part in a direct predictive test. Motives

for taking the test are the same as those mentioned in the

literature (certainty of carrier status, decisions concerning

marriage and further children, planning a career). Motives for

not taking the test mostly involve psychological problems in

coping with the test result. 45.7% wish to undergo a direct

prenatal test (main cause: certainty of the gene status of the

child), whereas 27% would not take this test (because of non-

toleration of abortion). Only statistical trends could be seen

between the intention to take the predictive or prenatal test

and some social and demographic variables. The at-risk

persons would not change their attitudes regarding indirect or

direct predictive and prenatal DNA analysis; they seem to have

a confirmed opinion about molecular genetics, mostly

depending on familial and social background.

93. Kugler, C. [Can age-dependent cognitive functions be measured?

P300 potentials--concept of brain aging--early diagnosis of

dementia processes]. Alternsabhangigkeit kognitiver

Funktionen messbar? P300-Potentiale--Verstandnis der

Gehirnalterung--Fruhdiagnostik dementieller Prozesse.

Fortschr-Med. 1996 Oct 10; 114(28): 357-60; ISSN: 0015-

8178.

GERMANY. Event related P300 potentials as the

electrophysiological substrate of cognitive functions, such as

the stimulus processing time (P300 latencies) and visual

attention capacity (P300 amplitudes) are suitable for the

analysis of age-related changes in cognitive human brain

functions. P300 investigations carried out in a total of 330

test subjects aged between 18 and 98 years, showed an overall

slight prolongation of the P300 latencies by 10 ms for each

decade, as well as a discrete reduction in the P300 amplitudes

of 1 microV. To describe the relationship between the P300

parameters and chronological age, polynomial regression

models are more suitable than linear functions. This means

that in middle-age, P300 potentials change only slightly

while, from about the age of 60 upwards, a noticeable

acceleration in the P300 changes takes place. An interesting

observation was the fact that the acceleration in the P300

latency increase occurred some 10 years earlier in women

than in men, beginning in the early postmenopausal period. The

polynomial course of the regression function for the age-

dependence of P300 potentials might reflect the positive

influence of socio-cultural factors on the aging of cognitive

functions. The true extent of the age-related changes in

cognitive functions, however, can be determined only with the

aid of intra-individual longitudinal studies. This is of

considerable importance for the early diagnosis of both

metabolic and primarily degenerative encephalopathies.

94. Kwasa, T. O. Neurological manifestations of human

immunodeficiency virus infection and acquired immune

deficiency syndrome: a review. East-Afr-Med-J. 1995 Oct;

72(10): 664-8; ISSN: 0012-835X.

KENYA. Neurological manifestations of HIV/AIDS is reviewed

and discussed. It is noted that neurological manifestations are

some of the commonest modes of clinical presentation of

HIV/AIDS. At autopsy, the prevalence approaches 100%. These

manifestations include: involvement of the higher functions,

craniopathies, spinal cord disease, peripheral neuropathy and

muscle disease. It is therefore stressed that the central

nervous system must be particularly assessed in patients with

HIV/AIDS and where the clinician is not sure of the

neurological diagnosis, a referral to the neurologist is

recommended as some of these are treatable.

95. Lamade, U. M.; Lamade, W.; Hess, T.; Gosztonyi, G.; Kehm, R.; Sartor,

K.; Hacke, W. A mouse model of herpes simplex virus

encephalitis: diagnostic brain imaging by magnetic resonance

imaging. In-Vivo. 1996 Nov; 10(6): 563-8; ISSN: 0258-851X.

GREECE. Herpes simplex virus encephalitis is a severe

sporadic encephalitis in man with high mortality and

morbidity. A critical step in the establishment of therapy is

early diagnosis. Magnetic resonance imaging is a noninvasive,

accurate diagnostic test for the detection of central nervous

system disease. In an effort to monitor morphological changes

in vivo we present a new diagnostic neuroimaging model of

experimental herpes simplex virus encephalitis. A mouse

model of herpes simplex virus encephalitis was used. 40 SJL

mice were intranasally inoculated with an infectious dose of

wild-type strain HSV-I F. Morphological abnormalities were

studied by cranial magnetic resonance imaging (MRI). These

findings were correlated with sequential neuropathological

studies. 95% of animals developed cerebral abnormalities on

MRI. resembling human HSVE. Areas of increased signal

intensity on T2-weighted sequences and focal pathological

contrast enhancement were mostly found in the frontal and

temporal lobes and thalamic and cerebellar regions. All

animals with MRI abnormalities had neuropathological signs of

neuronal degeneration and reactive astrocytosis in

corresponding regions. The described monitoring system offers

a new approach for studies on neurovirulence and therapeutic

strategies.

96. Lanzi, G.; Fazzi, E.; Veggiotti, P.; Pagliano, E.; Gariglio, M.;

Bonaglia, C.; Landolfo, S. Ring chromosome 9: an atypical case.

Brain-Dev. 1996 May; 18(3): 216-9; ISSN: 0387-7604.

NETHERLANDS. A new case of ring chromosome 9 in a 36-

month-old child is presented. In addition to the pathognomonic

features of this rare disorder (only 21 cases reported), our

patient presents some peculiarities, such as corpus callosum

hypoplasia and epileptic seizures (infantile periodic spasms).

We also observed a reduced level of leukocyte interferon alpha

whose synthesis is controlled by a gene on chromosome 9 and

which could be responsible for the recurrent respiratory tract

infections, typical and sometimes fatal in these patients.

97. Larson, P. J.; Lukas, M. B.; Friedman, D. F.; Manno, C. S. Delayed

hemolytic transfusion reaction due to anti-Go(a), an antibody

against the low-prevalence Gonzales antigen. Am-J-Hematol.

1996 Dec; 53(4): 248-50; ISSN: 0361-8609.

UNITED-STATES. Go(a) (D(Cor)) is a low-frequency antigen in

the Rh system found on red cells lacking part of the D mosaic

(category IVa). Anti-Go(a) has not been previously reported to

cause hemolytic transfusion reactions. A 27-year-old African

American male with sickle-cell disease, maintained on chronic

transfusion, was noted to have dark plasma during an

erythrocytapheresis, procedure, and the pretransfusion

hemoglobin was noted to be 1 g/dl lower than 4 weeks before

(with hyperbilirubinemia and a significantly increased LDH).

Polyspecific direct antiglobulin test (DAT) was weakly

positive (C3-weak, IgG-weak), and indirect antiglobulin tests

(IATs) performed on the serum (pre- and posttransfusion

reaction) and a red blood cell (RBC) eluate from the

postreaction sample were negative. A segment from one of the

four implicated units from the prior month's transfusion was

strongly reactive at 37 degrees C and using anti-human

globulin (AHG) when crossmatched with the postreaction

serum and the eluate. The postreaction serum, screened with a

panel of red cells positive for low-prevalence antigens,

reacted with three Go(a+) cells. The implicated unit was

reactive with a previously identified anti-Go(a) serum.. 0; 0;

98. Laywell, E. D.; Friedman, P.; Harrington, K.; Robertson, J. T.;

Steindler, D. A. Cell attachment to frozen sections of injured

adult mouse brain: effects of tenascin antibody and lectin

perturbation of wound-related extracellular matrix molecules.

J-Neurosci-Methods. 1996 Jun; 66(2): 99-108; ISSN: 0165-

0270.

NETHERLANDS. Previous studies describing the use of

cryoculture methods have focused on the efficacy of the

method for studying neuron attachment and neurite outgrowth

on intact sections of nerve, and rodent and even human brain.

The cryoculture method has shown promise for determining the

presence of cell attachment- and neurite-growth-inhibiting

molecules in such specimens, and some studies have also

attempted to neutralize such molecules with antibodies to

myelin inhibitory proteins, nerve growth factor, or factors

present in conditioned media that may counteract the

repulsiveness of some of these molecules preserved in

sections of, for example, myelinated nerves or adult brain

white matter. The present study describes the novel use of

lesioned central nervous system cryocultures as substrates

for investigating the attachment of embryonic neurons and

PC12 cells. In addition to demonstrating the use of this novel

scar substrate to extend previous 'scar-in-a-dish' models

(David et al. (1990) Neuron, 5:463-469; Rudge and Silver

(1990) J. Neurosci., 10: 3594-3603; Rudge et al. (1989) Exp.

Neurol., 103: 1-16), the present study also describes antibody

and lectin perturbations of putative inhibitory molecules that

result in an enhanced attachment of cells to cryosection

cultures of brain and spinal cord wounds.. 0; 0; 0; 0; 0; 0.

99. Lee, C. A. Transfusion-transmitted disease. Baillieres-Clin-

Haematol. 1996 Jun; 9(2): 369-94; ISSN: 0950-3536.

ENGLAND. Many patients with haemophilia are infected with

viruses, due to treatment with blood products--particularly

from large pool clotting factor concentrates before 1985. AIDS

in haemophilic patients was first described in 1982 and it has

significantly reduced the life expectancy of these patients.

Although no new sero-conversions have occurred since 1986,

management of HIV in haemophilia remains a clinical

challenge. Transfusion-associated hepatitis was recognized in

1943, and it is now an important complication of haemophilia

treatment. Vaccination against HAV is recommended.

Intensively-treated older haemophilic patients usually have

serological evidence of HBV infection. HBV transmission has

been stopped, but hepatitis B vaccination is still practised,

because HDV requires HBV for propagation. Many patients are

infected with HCV: before 1985 almost all patients who

received clotting factor concentrate developed non-A, non-B

hepatitis, now recognized as HCV. Treatment strategies are

being developed for HCV in haemophilic patients. Parvo virus

can be transmitted by clotting factor concentrate; it is very

resistant to sterilization processes, transmission causing

severe illness even in immuno-competent individuals. New

blood-borne viruses responsible for sero-negative hepatitis

include: GBV-A, B and C, and HGV. Although there is no link

between CJD and haemophilia, there is concern about possible

blood product transmission.. 0; 30516-87-1.

100. Lehky, T. J.; Flerlage, N.; Katz, D.; Houff, S.; Hall, W. H.; Ishii, K.;

Monken, C.; Dhib Jalbut, S.; McFarland, H. F.; Jacobson, S. Human

T-cell lymphotropic virus type II-associated myelopathy:

clinical and immunologic profiles. Ann-Neurol. 1996 Nov;

40(5): 714-23; ISSN: 0364-5134.

UNITED-STATES. Human T-cell lymphotropic virus type II

(HTLV-II) is endemic in several ethnic tribes and among

intravenous drug users in metropolitan areas. Despite the

presence of HTLV-II in these various populations, the

association of HTLV-II with disease is sparse and mainly

limited to isolated case reports. This study is an extension of

an earlier description of an HTLV-II-infected patient with

neurologic disease and presents the clinical and immunologic

findings of 4 patients with HTLV-II seropositivity and spastic

paraparesis. The patients are of African-American origin with

3 of the patients being of Amerindian descent. All of the

patients are seronegative for the human immunodeficiency

virus (HIV). The patients progressed to a nonambulatory state

in less than 5 years. Magnetic resonance imaging studies

obtained from 3 of the patients demonstrated white matter

disease in the cerebrum and spinal cord. The cerebrospinal

fluid and serum contained antibodies to HTLV-II. The presence

of proviral HTLV-II was confirmed by polymerase chain

reaction analysis of peripheral blood lymphocytes (PBLs). A

spinal cord biopsy from 1 patient demonstrated HTLV RNA

within a lesion. Immunologic studies on 2 patients

demonstrated that spontaneous lymphoproliferation of PBLs

was present but decreased relative to HTLV-I-infected

patients. The clinical and immunologic findings from these

HTLV-II-infected patient resemble those found in HTLV-I-

associated myelopathy/tropical spastic paraparesis.. 0; 0.

101. Lehrnbecher, T.; Chittka, B.; Nanan, R.; Seidenspinner, S.; Kreth, H.

W.; Schuster, V. Activated T lymphocytes in the cerebrospinal

fluid of a patient with Epstein-Barr virus-associated

meningoencephalitis. Pediatr-Infect-Dis-J. 1996 Jul; 15(7):

631-3; ISSN: 0891-3668.

UNITED-STATES. 0; 0; 0.

102. Lewko, J. P.; Stokic, D. S.; Tarkka, I. M. Dissociation of cortical

areas responsible for evoking excitatory and inhibitory

responses in the small hand muscles. Brain-Topogr. 1996 Jun;

8(4): 397-405; ISSN: 0896-0267.

UNITED-STATES. Noninvasive transcranial magnetic

stimulation (TMS) of the brain using a focal eight-shaped coil

with 100% stimulation output was performed in eleven healthy

subjects to find out if excitatory and inhibitory responses in

the small hand muscles could be dissociated. Motor evoked

potentials (MEP) as well as silent periods (SP) were recorded

from the right abductor pollicis brevis (APB), and first dorsal

interosseus (FDI) muscles at rest and during weak voluntary

contraction. Mapping of the cortical representation area was

performed over different scalp locations on the left

hemisphere. The cortical representation maps for ABP and FDI

recorded during contraction covered much larger area and were

more elongated in the anterior-posterior than in the medial-

lateral direction compared to maps obtained during relaxation.

The distribution maps for SPs covered larger scalp areas

compared to the maps of MEPs obtained during voluntary

contraction. Also during voluntary contraction the locations

for evoking the longest SPs were not identical to locations for

evoking the peak MEP amplitudes; the longest SPs were

observed during stimulation of more medial and frontal

locations compared to peak MEPs. Interestingly, stimulation of

some locations resulted in the appearance of an isolated MEP

without the following SP and in other locations an isolated SP

was recorded. The areas for evoking isolated MEPs were in the

center, whereas the areas for isolated SPs were located in the

periphery of the map. Features such as exclusive locations for

MEPs and SPs, and different locations for peak MEP amplitudes

and longest SPs, suggest dissociation of the excitatory and

inhibitory cortical processes evoked by transcranial magnetic

stimulation during voluntary contraction.

103. Lipkin, W. I. European consensus on viral encephalitis. Lancet.

1997 Feb 1; 349(9048): 299-300; ISSN: 0140-6736.

ENGLAND. 0; 0; 59277-89-3.

104. Loscher, W.; Honack, D. Intravenous carbamazepine: comparison of

different parenteral formulations in a mouse model of

convulsive status epilepticus. Epilepsia. 1997 Jan; 38(1): 106-

13; ISSN: 0013-9580.

UNITED-STATES. PURPOSE: A drawback of carbamazepine

(CBZ), a major antiepileptic drug (AED) with clinical efficacy

against partial and generalized convulsive seizures, is its

isolubility in aqueous vehicles, which is generally considered

a contraindication to parenteral administration in epileptic

patients. However, CBZ can be dissolved in glycofurol, a

solvent used clinically as a vehicle for parenteral preparations

of drugs such as diazepam (DZP) and phenytoin (PHT).

Furthermore, aqueous CBZ solutions can be prepared by

complexing CBZ with 2-hydroxypropyl-beta-cyclodextrin (HP

beta CD), an inert beta-cyclodextrin derivative believed to

have acceptable tolerability for human use. Such solutions of

CBZ have been proposed to be suitable for intravenous

administration in treatment of convulsive (grand mal) status

epilepticus (CSE). METHODS: A series of five generalized tonic-

clonic seizures (GTCS) in 30 min was induced by repeated

transauricular electrical stimulation in mice. In this model of

convulsive (grand mal) SE, the anticonvulsant potency of

intravenous CBZ dissolved in aqueous dilutions of either HP

beta CD or glycofurol was evaluated. RESULTS: In both

solutions, CBZ rapidly suppressed seizures after intravenous

bolus injection. Potent anticonvulsant activity was obtained

as early as 30 s after injection, and peak effects were

observed at approximately 3 min. ED50 for blockade of GTCS

throughout the 30-min period of repeated electrical

stimulation was approximately 7 mg/kg, similar to the

potency of DZP in this model. Whereas the HP beta CD/CBZ

solutions were tolerated by the animals, with no pronounced

behavioral or motor adverse effects, the glycofurol/CBZ

solutions induced marked sedation and motor impairment,

indicating interactions between drug and solvent.

Determination of CBZ in plasma and brain demonstrated that

the rapid onset of anticonvulsant action after intravenous

bolus injection was related to rapid drug penetration into

brain tissue. CONCLUSIONS: An intravenous formulation of CBZ

achieved through complexing with HP beta CD might be

suitable for parenteral use in acute clinical conditions such as

SE, particularly because CBZ has the advantage of being almost

free of respiratory or cardiovascular adverse effects.. 0; 0; 0;

0; 0; 298-46-4; 9004-76-6; 94035-02-6.

105. Mandich, P.; Di Maria, E.; Bellone, E.; Ajmar, F.; Abbruzzese, G.

Molecular analysis of the IT15 gene in patients with

apparently 'sporadic' Huntington's disease. Eur-Neurol. 1996;

36(6): 348-52; ISSN: 0014-3022.

SWITZERLAND. The diagnosis of Huntington's disease (HD) may

be uncertain in patients without a positive family history,

particularly when atypical clinical features are present. We

examined the expanded trinucleotide (CAG) repeat sequence in

the IT15 gene of 27 'sporadic' cases, classified as having

clinically probable or clinically doubtful HD. An abnormal

number of CAG repeats (42-85) were found in 14 patients.

Mutation analysis confirmed the diagnosis in 63.6% of patients

with clinically probable HD and in 43.7% of patients with

clinically doubtful HD. DNA analysis allows an accurate

diagnosis of apparently 'sporadic' HD patients and has

important implications for genetic counselling.

106. Marshall, J. W.; Ridley, R. M. Assessment of functional impairment

following permanent middle cerebral artery occlusion in a

non-human primate species. Neurodegeneration. 1996 Sep; 5(3):

275-86; ISSN: 1055-8330.

ENGLAND. The purpose of the present study was to examine

and quantify the functional consequence of a focal cerebral

ischaemic lesion in a primate species, the marmoset.

Following craniotomy and retraction of the frontal and

temporal lobes, the middle cerebral artery was permanently

occluded by means of electrocoagulation. Three and eight

weeks after surgery, various behavioural tests were used to

give a quantifiable measure to the neurological deficits

produced. These tests required the monkeys to reach into tubes

for foodbits, retrieve rewards from the steps of two designs

of 'staircases', respond to one of two simultaneously

presented rewarded tubes, remove adhesive labels attached to

their feet, and respond to sensory stimuli. Unilateral motor

impairment of the contralateral forelimb and neglect of

contralateral tactile stimuli were seen in all subjects, and

spatial neglect was also present in some monkeys. Subsequent

histological analysis revealed unilateral cortical damage in all

subjects with varying amounts of injury to the caudate and the

putamen in some animals. These results demonstrate the

potential for the use of this species in future investigations

to examine the effect of neuroprotective treatment on

functional outcome after a focal ischaemic insult.

107. Mathern, G. W.; Kuhlman, P. A.; Mendoza, D.; Pretorius, J. K. Human

fascia dentata anatomy and hippocampal neuron densities

differ depending on the epileptic syndrome and age at first

seizure. J-Neuropathol-Exp-Neurol. 1997 Feb; 56(2): 199-212;

ISSN: 0022-3069.

UNITED-STATES. This study determined fascia dentata

anatomy and hippocampal neuron densities in patients with

different epileptic syndromes. Based on presurgical data,

patients were classified into: (a) pediatric patients (n=19); (b)

temporal mass lesion cases (n=14); and (c) hippocampal

sclerosis patients (n=31). Surgically removed hippocampi and

autopsies (n=34) were studied for: (a) hippocampal neuron

densities; (b) stratum granulosum (SG) widths and lengths; and

per tissue section were estimated from the neuron densities

and fascia dentata area measurements. Results showed that

compared with autopsies (p<0.05): (a) pediatric patients had

similar SG and hilar areas; granule cell density was lower (but

not hilar neuron density); and the estimated number of granule

cells was lower (but not the number of hilar neurons); (b) the

widths of SG and hilar areas were greater in mass lesion

cases; the density of granule cells and hilar neurons was

lower; and the total estimated numbers of granule cells and

hilar neurons were similar to those of the autopsies; and (c)

hippocampal sclerosis patients had wider, yet shorter SG;

hilar areas were smaller; granule cell and hilar densities were

lower; and the total estimated numbers of granule cells and

hilar neurons were lower than those of the autopsy cases. The

duration of the seizures did not correlate with lower fascia

dentata neuron densities or estimates of total granule cell and

hilar neurons. Furthermore, greater SG widths correlated with

lower hilar and CA4 neuron densities, but not with age at first

seizure or duration of epilepsy. These results indicate that the

size of the fascia dentata SG and hilus along with hippocampal

neuron densities differ between surgical patients with

different epileptic syndromes, and a wider SG was associated

with a lower density of end folium neurons. These findings

support the hypothesis that hippocampal sclerosis and granule

cell dispersion are not the consequence of repetitive seizures

beginning at an early developmental age, but seem to differ

depending on the type of epileptic syndrome.

108. Matsumoto, C.; Nara, Y.; Ikeda, K.; Tamada, T.; Mashimo, T.; Nabika,

T.; Sawamura, M.; Yamori, Y. Cosegregation of the new region on

chromosome 3 with salt-induced hypertension in female F2

progeny from stroke-prone spontaneously hypertensive and

Wistar-Kyoto rats. Clin-Exp-Pharmacol-Physiol. 1996 Dec;

23(12): 1028-34; ISSN: 0305-1870.

AUSTRALIA. 1. We investigated candidate loci for salt-

sensitive high blood pressure (BP) in F2 progeny from crossing

Wistar-Kyoto and stroke-prone spontaneously hypertensive

rats. 2. In female F2 progeny, systolic and diastolic BP on the

12th day and the seventh month after salt loading was

strongly linked with the D3Mgh12 and D3Mgh6 loci on

chromosome 3, respectively. 3. These loci were linked with BP

only in female F2 progeny, not in males. 4. These results

indicate that hormonal factors may influence salt sensitivity,

particularly with respect to gender differences.. 0; 7647-14-

109. Mercader Sobreques, J. M.; Berenguer Gonzalez, J.; Pujol Farre, T.

[Diagnosis by imaging of the brain affected by AIDS].

Diagnostico por imagen de la afectacion cerebral en el SIDA.

Rev-Neurol. 1996 Dec; 24(136): 1577-89; ISSN: 0210-0010.

SPAIN. Neurological complications are frequent in patients

with the acquired immunodeficiency syndrome (AIDS). They are

caused by neural structures being affected by the virus itself,

and/or the development of opportunist infections and

neoplasias secondary to the immunodepression. Cerebral

toxoplasmosis and human immunodeficiency virus (HIV)

encephalopathy are the commonest encephalopathic disorders

seen in these patients. Primary cerebral lymphoma,

progressive multifocal leukoencephalopathy (PML),

tuberculosis, etc. are less common. Computerized tomography

(CT) and magnetic resonance (MR) are the most suitable

techniques for diagnosis and follow-up of cerebral

involvement in patients with AIDS. Although MR is more

sensitive for the detection of lesions, particularly those in the

white matter, CT is still the most widely used technique since

its more readily available. Also it needs less cooperation from

the patient. Although on some occasions combination of both

techniques may suggest the aetiology of the lesion, these

techniques are non-specific.

110. Mesulam, M. M. The systems-level organization of cholinergic

innervation in the human cerebral cortex and its alterations in

Alzheimer's disease. Prog-Brain-Res. 1996; 109: 285-97; ISSN:

0079-6123.

NETHERLANDS. EC 2.3.1.6; 51-84-3.

111. Mizoi, K.; Yoshimoto, T.; Takahashi, A.; Nagamine, Y. A pitfall in

the surgery of a recurrent aneurysm after coil embolization

and its histological observation: technical case report.

Neurosurgery. 1996 Jul; 39(1): 165-8; discussion 168-9; ISSN:

0148-396X.

UNITED-STATES. OBJECTIVE AND IMPORTANCE: This case

report details the unexpected surgical difficulty encountered

in treating a recurrent aneurysm after coil embolization and

presents the histological findings of the resected aneurysm.

This is only the second reported case of histological

description of an aneurysm after coil embolization in a human.

CLINICAL PRESENTATION: A 60-year-old woman experienced a

3-month history of chronic headache. Neuroimaging studies

demonstrated a 2-cm anterior communicating artery aneurysm.

The aneurysm was treated with a two-stage endovascular coil

embolization, resulting in almost complete occlusion of the

aneurysm. A cerebral angiogram at 6-month follow-up

demonstrated slight refilling of the aneurysm, and angiography

at 18 months showed a marked increase in the size of the

small remnant. Therefore, the patient was referred for direct

surgical repair of the aneurysm. INTERVENTION: The distal

aneurysm dome, which had been packed with the coils and

thrombus, was resected under temporary arterial trapping. An

intra-aneurysmal endarterectomy was required, because the

aneurysm wall developed intimal dissection that extended to

the orifices of afferent and efferent arteries. The aneurysm

was then obliterated with multiple clips, reconstructing the

patent vessel lumen. However, the patient awoke from surgery

with left hemiparesis. A postoperative angiogram disclosed

occlusion of the right anterior cerebral artery. An histological

study of the thrombosed aneurysm showed that the luminal

surface of thrombus was not lined by endothelium.

CONCLUSION: This case demonstrated not only the limited

efficacy of coil embolization treatment for wide-necked

aneurysms but also the potential difficulty in the direct

surgical repair for such recurrent aneurysms.

112. Modayur, B. R.; Prothero, J.; Rosse, C.; Jakobovits, R.; Brinkley, J. F.

Visualization and mapping of neurosurgical functional brain

data onto a 3-D MR-based model of the brain surface. Proc-

AMIA-Annu-Fall-Symp. 1996; : 304-8.

UNITED-STATES. The Human Brain Project was initiated with

the goal of developing methods for managing and sharing

information about the brain. As a prototype Human Brain

Project application we are developing a system for organizing,

visualizing, integrating and sharing information about human

language function. The goal of the brain mapping component of

our work, described in this article, is to generate the 3D

location and extent of cortical language sites with respect to

a uniform, 3D patient coordinate system. The language sites of

individual patients can then be combined with or related to

other patient data in terms of a Talairach, surface-based, or

other deformable coordinate systems. Language site mapping

is done by visually comparing an intraoperative photograph

with the rendered image (from MRI data). The techniques

outlined in this article have been utilized to map cortical

language sites of six patients. Preliminary results point to the

adequacy of our volume visualizations for language mapping.

The strength of the visualization scheme lies in the

combination of interactive segmentation with volume and

surface visualization. We are now in the process of acquiring

more patient data to further validate the usefulness of our

method.

113. Morrell, M. J. The new antiepileptic drugs and women: efficacy,

reproductive health, pregnancy, and fetal outcome. Epilepsia.

1996; 37 Suppl 6: S34-44; ISSN: 0013-9580.

UNITED-STATES. As new antiepileptic drugs (AEDs) become

available, physicians will define their appropriate use in

particular patient populations. For women, the issues include

gender-specific efficacy and tolerability, including the impact

of the AED on reproductive health. Women with epilepsy who

are treated with established AEDs appear to be at risk for

compromised bone health, for disturbances in fertility,

menstrual cyclicity, ovulatory function, and sexuality and,

with some AEDs, for failure of hormonal contraception.

Finally, pregnancy outcome may be adversely affected by the

established AEDs, all of which are human teratogens.

Felbamate (FBM), gabapentin (GBP), lamotrigine (LTG),

oxcarbazepine (OCBZ), tiagabine (TGB), topiramate (TPM), and

vigabatrin (VGB) were reviewed. The preclinical development

process had not addressed all the issues of concern to women.

Although gender-specific efficacy is routinely evaluated,

impact on reproductive health is not. FBM, GBP, LTG, TGB, TPM,

and VGB have similar efficacy in women and men. It is not

known whether the new AEDs will affect bone health, fertility,

the menstrual cycle, and sexuality. FBM, GBP, LTG, TGB, and

probably VGB do not interfere with hormonal contraception.

Whether these new AEDs are good choices for the pregnant

woman with epilepsy awaits further experience in human

pregnancy. However, animal reproductive toxicology studies

appear promising. The limited number of human pregnancy

exposures do not, thus far, signal a significant number or

particular type of adverse outcomes. However, only with

improved postmarketing surveillance can essential

information about teratogenic effects by acquired in an

acceptably short time.. 0; 0; 0.

114. Moser, E.; Teichtmeister, C.; Diemling, M. Reproducibility and

postprocessing of gradient-echo functional MRI to improve

localization of brain activity in the human visual cortex. Magn-

Reson-Imaging. 1996; 14(6): 567-79; ISSN: 0730-725X.

UNITED-STATES. High reproducibility of human FMRI studies is

imperative for potential clinical applications of this new

method for mapping human brain functions. So far, published

data are not comparable quantitatively (even at the same field

strength) as differences in sequence design and parameters as

well as statistical methods applied to enhance function

related image contrast, in particular, to extract the size of

the "activated areas," are manifold. We present a study on

reproducibility of gradient-echo FMRI in the human visual

cortex using the different threshold strategies for correlation

analysis that shows that, (a) applying adaptive correlation

thresholds results in higher reproducibility compared to a

fixed (0.5) threshold; (b) highly reproducible data can be

obtained on a clinical 1.5 T MRI system, at least for repeated

single subject studies (i.e., standard deviation of 2-30% for

signal enhancement in 72-94% of the studies and 5-50% for

activated area size in 63-88% of the studies, respectively,

depending on threshold strategies); however, depending also on

subject cooperation; (c) reproducibility across groups (alpha =

const.) is worse, i.e., standard deviations are within 33-45%

for signal enhancement and 41-74% for activated area size,

respectively; (d) SNR is maximum at about 30 degrees flip

angle, suggesting significant contributions from T1-effects

for larger flip angles. Various technical, methodological, and

physiological factors are influencing variability of signal

enhancement and apparently activated area size, which should

be taken into account if interpreting FMRI data quantitatively.

115. Mullner, M.; Sterz, F.; Domanovits, H.; Zeiner, A.; Laggner, A. N.

Systemic and cerebral oxygen extraction after human cardiac

arrest. Eur-J-Emerg-Med. 1996 Mar; 3(1): 19-24; ISSN: 0969-

9546.

ENGLAND. The aim of this study was to observe cerebral and

systemic oxygen extraction after human cardiac arrest with

return of spontaneous circulation. Eight adult patients after

non-traumatic, cardiac arrest were included. Cerebral and

systemic oxygen extraction ratios were measured together

with haemodynamic variables beginning 2 hours after cardiac

arrest and every 4 hours thereafter until 24 hours. Between 2

and 12 hours after cardiac arrest cerebral oxygen extraction

values ranged from very low over normal to very high. In the

further course these values were reduced until 24 hours in six

patients. Two patients who were still alive after 6 months,

both severely mentally disabled, had a higher cerebral oxygen

extraction ratios in comparison with non-survivors. Systemic

oxygen extraction seemed to vary more than the cerebral

oxygen extraction. The two long-term survivors had normal to

supranormal values from 8 to 24 hours. In conclusion cerebral

oxygen extraction was higher in long-term cardiac arrest

survivors than in non-survivors between 12 and 24 hours after

the event. Further, a better quality of neurological recovery

was associated with higher cerebral oxygen extraction.

Systemic oxygen extraction was also impaired, but to a lesser

extent, especially in long-term survivors.

116. Murakami, T.; Ohtsuka, A.; Piao, D. X. Perineuronal sulfated

proteoglycans in the human brain are identical to Golgi's

reticular coating. Arch-Histol-Cytol. 1996 Aug; 59(3): 233-7;

ISSN: 0914-9465.

JAPAN. Many neurons in the human somatosensory cortex

(Area 7 of Brodmann) possess an intensely negative-charged

surface coat consisting of perineuronal sulfated proteoglycans

which were stained with cationic iron colloid. This surface

coat was stained doubly with cationic iron colloid and Golgi's

silver nitrate. The result indicates that the perineuronal

sulfated proteoglycans are identical with Golgi's reticular

coating, whose existence and nature have previously been

controversial. The result also suggests that Golgi's silver

nitrate stains the core proteins of proteoglycans.. 0; 0; 0; 0;

7439-89-6.

117. Nagasawa, H.; Tanji, H.; Itoh, M.; Itoyama, Y. [PET study using 6-

[18F]-fluorodopa in Parkinson's disease]. Nippon-Rinsho. 1997

Jan; 55(1): 213-7; ISSN: 0047-1852.

JAPAN. 6-[18F]-fluorodopa (FDOPA) was developed as an

analogue of L-DOPA across the blood-brain-barrier and to

carry into nigrostriatal dopaminergic neurons. PET study using

FDOPA revealed presynaptic dopaminergic function in the

striatum of nigrostriatal system of the human brain and many

studies have performed to clarify the pathogenesis of

Parkinson's disease. FDOPA is also an efficient tracer to

analyze pharmacokinetics of L-DOPA by measuring

radioactivities of its metabolites in the peripheral blood by

HPLC and to evaluate pharmacological effects on dopamine

metabolism by pretreatment of dopa decarboxylase inhibitor or

COMT inhibitor. PET study using FDOPA is useful not only to

diagnose Parkinson's disease but also to differentiate from

parkinsonism in combination with other radioactive ligands

and with other neuroimaging methods such as MRI.. 0; 51-61-

6; 63-84-3; 75290-51-6.

118. Naito, E.; Ito, M.; Yokota, I.; Saijo, T.; Matsuda, J.; Osaka, H.;

Kimura, S.; Kuroda, Y. [Defects of pyruvate metabolism in

cultured lymphoblastoid cells of 20 patients with Leigh

syndrome]. No-To-Hattatsu. 1996 Nov; 28(6): 495-500; ISSN:

0029-0831.

JAPAN. Lymphoblastoid cells are useful materials for the

diagnosis and basic studies of many human genetic disorders.

To elucidate the etiology of Leigh syndrome, biochemical

analyses and mitochondrial DNA analyses were performed on

cultured lymphoblastoid cells from 20 patients with the

clinical characteristics of this disorder. In 9 of 20 cases, we

were able to define the following defects. Eight patients had

biochemical defects, including 3 with pyruvate dehydrogenase

complex (PDHC), 3 with cytochrome c oxidase (complex IV),

and 2 with NADH-cytochrome c reductase (complex I)

deficiencies. Two of 3 patients with PDHC deficiency were

diagnosed with thiamine-responsive PDHC deficiency. One

patient had a point mutation (T-->G) of mitochondrial DNA at

nucleotide position 8993. These results indicate that the

underlying defects in Leigh syndrome are heterogeneous and

cultured lymphoblastoid cells are very useful materials for

diagnosis of the etiology of Leigh syndrome.. EC 1.6.99.3; EC

1.9.3.1; 0; 0; 127-17-3.

119. Nakasato, N.; Seki, K.; Fujita, S.; Hatanaka, K.; Kawamura, T.;

Ohtomo, S.; Kanno, A.; Ikeda, H.; Yoshimoto, T. Clinical

application of visual evoked fields using an MRI-linked whole

head MEG system. Front-Med-Biol-Eng. 1996; 7(4): 275-83;

ISSN: 0921-3775.

NETHERLANDS. We have demonstrated anatomo-functional

correlation of the brain visual function using an MRI-linked

whole-head magnetoencephalography system. Visual evoked

magnetic fields (VEFs) due to pattern reversal stimuli were

measured in seven healthy subjects and 13 patients with

intracranial structural lesions. Full-field stimuli evoked the

most prominent peak around 100 ms latency (P100m) as a

two-dipole pattern over the occipital area in all of the normal

subjects and four patients with mild and partial hemianopsia.

In five patients with homonymous hemianopsia due to

unilateral occipital lesion, a single-dipole pattern of the

P100m appeared over the normal occipital area only. In four

patients with bitemporal hemianopsia due to pituitary tumors,

a single-dipole pattern of the P100m appeared only over the

ipsilateral occipital area to the stimulated eye. Using current

dipole models, P100m sources were localized at the lateral

bottom of the calcarine fissures. Although human occipital

lobes are known to be morphologically variable, our results

indicate excellent correlation of the cortical anatomy and

human visual function. Full-field stimuli, requiring no strict

visual fixation, are especially useful for clinical application.

A clear two-dipole pattern in the normal VEFs enables us to

compare two hemispheric activities.

120. Nakashima, K.; Watanabe, Y.; Kusumi, M.; Nanba, E.; Maeoka, Y.; Igo,

M.; Irie, H.; Ishino, H.; Fujimoto, A.; Kobayashi, S.; et, a. l.

[Prevalence and founder effect of Huntington's disease in the

San-in area of Japan]. Rinsho-Shinkeigaku. 1995 Dec; 35(12):

1532-4; ISSN: 0009-918X.

JAPAN. After the DNA diagnosis, we evaluated the prevalence

of Huntington's disease (HD) in the San-in area of Japan, and

confirmed the founder effect. The population of the area was

1,387,000 on October 1st, 1993. There were 10 patients with

HD in the San-in area, who were diagnosed clinically. They all

had involuntary movement, mental disturbance, changes of

character and atrophy of the caudate nucleus. However, one of

the patients showed no positive family history of HD. The

other nine patients had members with HD in their families,

although those family members of the patients had already

died. The expansion of the CAG repeat was observed in nine of

the patients. In the patient who had no positive family history,

expansion of the CAG repeat was not seen. According to the

nine patients with expansion of the CAG repeat, the prevalence

was 0.65/100,000. Haplotypes using polymorphism markers of

D4S111 and D4 S136 were studied. The haplotypes which were

observed in only 2.7% of the normal population were shown in

all nine HD patients. Thus, the obvious disequilibrium was

seen. These results suggested a common ancestor of these HD

patients.

121. Nielsen, J. E.; Sorensen, S. A.; Hasholt, L.; Norremolle, A.

Dentatorubral-pallidoluysian atrophy. Clinical features of a

five-generation Danish family. Mov-Disord. 1996 Sep; 11(5):

533-41; ISSN: 0885-3185.

UNITED-STATES. We describe the first Danish family with

dentatorubral-pallidoluysian atrophy (DRPLA), containing 16

clinically affected individuals in five generations. Inheritance

is autosomal dominant. The disorder was diagnosed as

Huntington's disease (HD), but analysis of the IT15 gene for HD

revealed normal alleles. The diagnosis of DRPLA was based on

the finding of elongated CAG repeats in the B37 gene on

chromosome 12 in affected individuals. The age at onset

ranged from 13 to 60 years, with the most severe clinical

picture being associated with onset in childhood. Clinical

features included varying combinations of dementia, euphoria,

visuomotor disturbances, speech problems, ataxia, tremor,

epilepsy and involuntary movements presenting as chorea,

athetosis, and dystonia. We discuss characteristics of DRPLA

that may enable the differentiation from HD on a clinical

basis. In conclusion, DRPLA should be considered and DNA

analysis is recommended in patients manifesting varying

combinations of extrapyramidal and cerebellar symptoms,

especially when clinical features show pronounced

intrafamilial variability, and dyscoordination, tremor,

myoclonus, epilepsy, and euphoria are part of the syndrome.

122. Nishimura, M.; Saida, T.; Kuroki, S.; Kawabata, T.; Obayashi, H.;

Saida, K.; Uchiyama, T. Post-infectious encephalitis with anti-

galactocerebroside antibody subsequent to Mycoplasma

pneumoniae infection. J-Neurol-Sci. 1996 Sep 1; 140(1-2): 91-

5; ISSN: 0022-510X.

NETHERLANDS. Galactocerebroside (Gc) is a major component

of myelin in both the peripheral and central nervous systems.

Although it is regarded as an important glycolipid hapten of

myelin in rabbit experimental allergic neuritis (EAN), its role

in human demyelinating diseases is not known. We studied

three post-infectious encephalitis (PIE) patients related to

Mycoplasma pneumoniae infection. All three of three patients

with encephalitis and M. pneumoniae infection were positive

for Gc antibodies (100%), while 25% of 32 M. pneumoniae-

infected patients without neurological disease were positive,

and 3.8% of 52 healthy controls. This indicates anti-Gc

antibody is induced by M. pneumoniae infection. One of the PIE

patients, who had extraordinary high titer antibody to Gc,

showed an extensive, diffuse white matter demyelination and

poor recovery. Since circulating anti-Gc antibody induces

central nervous system demyelination in animals with

elevated antibody titers and disruption of the blood-brain

barrier, anti-Gc antibody may have an important function in

the increased demyelination in PIE patients after M.

pneumoniae infection.. 0; 0; 0.

123. Ogasawara, N. [Complete and partial deficiency of HPRT]. Nippon-

Rinsho. 1996 Dec; 54(12): 3315-20; ISSN: 0047-1852.

JAPAN. The Lesch-Nyhan syndrome results from a complete or

virtually complete deficiency of the purine salvage enzyme,

hypoxanthine guanine phosphoribosyl transferase (HPRT). The

disease is characterized by hyperuricemia, choreoathetosis,

spasticity, compulsive self-mutilation, and mental

retardation. Patients with a partial deficiency of HPRT are

spared most of the neurological disorder of Lesch-Nyhan

syndrome. The specific relationship between HPRT deficiency

and the neurological dysfunction in the Lesch-Nyhan syndrome

is not known, at present. The genetic lesion which result in

HPRT deficiency are heterogeneous. About 90 different

mutations were found in over 110 families. The DNA-based

mutation detection technique can be used for the diagnosis of

affected males and for the determination of carrier status of

asymptomatic females. This technique is also applicable for

the prenatal diagnosis for Lesch-Nyhan syndrome. Transgenic

mice, deficient in HPRT activity, have been obtained but they

do not show any neurological dysfunction. After administration

of 9-ethyladenine, however, they showed the self-injury

behavior.. EC 2.4.2.8; 2715-68-6; 73-24-5; 9007-49-2.

124. Ohtsuka, M.; Miyazaki, M.; Kondo, Y.; Nakajima, N. Neutrophil-

mediated sinusoidal endothelial cell injury after extensive

hepatectomy in cholestatic rats. Hepatology. 1997 Mar; 25(3):

636-41; ISSN: 0270-9139.

UNITED-STATES. The aim of this study was to assess the

hypothesis that hepatic failure after extensive hepatectomy in

patients with obstructive jaundice (OJ) may be mediated by

polymorphonuclear neutrophils (PMN). In the OJ group, rats

underwent a partial hepatectomy of 78% after 2 weeks of

cholestasis and subsequent external biliary drainage for 5

days. In the sham-operated control group, rats were partially

hepatectomized 19 days after the sham surgery. The

concentration of the serum cytokine-induced neutrophil

chemoattractant (CINC), which is homologous with the

growth-related oncogene (gro) product, a member of the human

interleukin (IL)-8 family, and a major neutrophil chemotactic

factor in rats, increased concomitantly with accumulation of

PMNs in the hepatic sinusoids during cholestasis and

subsequent external drainage. However, changes in the serum

purine nucleoside phosphorylase (PNP)/alanine transaminase

(ALT) ratio as a marker of sinusoidal endothelial cell (SEC)

injury showed no significant differences between the two

groups. Intercellular adhesion molecule-1 (ICAM-1) expression

on SECs was not affected by cholestasis and external drainage.

After partial hepatectomy, the serum CINC concentration

immediately elevated more prominently in the OJ group than in

the sham-operated control group, and accumulation of PMNs in

the sinusoids was more obvious and prolonged in the former.

ICAM-1 expression was enhanced in both groups with a peak

between 24 and 48 hours after partial hepatectomy. At this

peak period, a significantly higher PNP/ALT ratio was

observed in the OJ group. These results suggest that

accumulation of PMNs in the sinusoidal space and ICAM-1

expression on SECs might be closely associated with the

development of SEC injury after extensive hepatectomy in

cholestasis.. EC 2.6.1.1; EC 2.6.1.2; 0; 0; 0; 126547-89-5.

125. Ophoff, R. A.; Terwindt, G. M.; Vergouwe, M. N.; van Eijk, R.; Oefner,

P. J.; Hoffman, S. M.; Lamerdin, J. E.; Mohrenweiser, H. W.;

Bulman, D. E.; Ferrari, M.; Haan, J.; Lindhout, D.; van Ommen, G.

J.; Hofker, M. H.; Ferrari, M. D.; Frants, R. R. Familial hemiplegic

migraine and episodic ataxia type-2 are caused by mutations

in the Ca2+ channel gene CACNL1A4. Cell. 1996 Nov 1; 87(3):

543-52; ISSN: 0092-8674.

UNITED-STATES. Genes for familial hemiplegic migraine (FHM)

and episodic ataxia type-2 (EA-2) have been mapped to

chromosome 19p13. We characterized a brain-specific P/Q-

type Ca2+ channel alpha1-subunit gene, CACNL1A4, covering

300 kb with 47 exons. Sequencing of all exons and their

surroundings revealed polymorphic variations, including a

(CA)n-repeat (D19S1150), a (CAG)n-repeat in the 3'-UTR, and

different types of deleterious mutations in FHM and EA-2. In

FHM, we found four different missense mutations in conserved

functional domains. One mutation has occurred on two

different haplotypes in unrelated FHM families. In EA-2, we

found two mutations disrupting the reading frame. Thus, FHM

and EA-2 can be considered as allelic channelopathies. A

similar etiology may be involved in common types of migraine..

0; 0.

126. Pahan, K.; Smith, B. T.; Singh, I. Epoxide hydrolase in human and

rat peroxisomes: implication for disorders of peroxisomal

biogenesis. J-Lipid-Res. 1996 Jan; 37(1): 159-67; ISSN: 0022-

2275.

UNITED-STATES. To understand the basis of excretion of

excessive amounts of epoxydicarboxylic fatty acids (EDFA) in

urine of patients with disorders of peroxisomal biogenesis

(Pitt, J. J., and A. Poulos. 1993. Clin. Chim. Acta. 223: 23-29),

the activity of epoxide hydrolase (EH) was measured in

cultured skin fibroblasts from control subjects and patients

with peroxisomal disorders. EH activity was approximately

40% lower in fibroblasts that lack intact peroxisomes

(Zellweger syndrome), whereas the activity in other

peroxisomal disorders (X-adrenoleukodystrophy and rhizomelic

chondrodysplasia punctata) with intact peroxisomes was

similar to control. To identify the specific enzyme/organelle

that represents the decrease in EH activity in Zellweger cells,

we have analyzed this activity in different subcellular

organelles from control and Zellweger skin fibroblasts. EH

activity was enriched in peroxisomes from control fibroblast.

EH activity in isolated mitochondria, microsomes, or cytosol

from Zellweger fibroblast was similar to that of control

fibroblast. These observations indicate that deficient activity

of EH in cells from Zellweger patients is due to lack of

peroxisomal EH activity. The peroxisomal EH is differentially

induced to a higher degree by ciprofibrate, a hypolipidemic

agent and peroxisome proliferator, than EH activity in other

organelles and cytoplasm. The high specific activity of EH in

peroxisomes and differential induction of EH activity in

peroxisomes as compared to other organelles, and the

excretion of EDFA in patients who lack peroxisomes suggests

that peroxisomal EH may be responsible for the detoxification

of EDFA, and that this enzyme in peroxisomes may be a

different protein than the EH found in other organelles.. EC

3.3.2.3.

127. Palha, J. A.; Moreira, P.; Wisniewski, T.; Frangione, B.; Saraiva, M.

J. Transthyretin gene in Alzheimer's disease patients.

Neurosci-Lett. 1996 Feb 9; 204(3): 212-4; ISSN: 0304-3940.

IRELAND. Amyloid beta (Abeta) is known to be the main

component of Alzheimer's disease (AD) senile plaques. A

homologous peptide is a normal component of biological fluids

and is called soluble Abeta (sAbeta). Synthetic peptides

homologous to Abeta form amyloid-like fibrils in vitro. This

fibril formation can be inhibited by normal human

cerebrospinal fluid (CSF) [Wisniewski et al., Ann. Neurol. 34

(1993)]. Furthermore, it has been proposed that normal

transthyretin (TTR), which is a component of CSF, can itself

bind sAbeta, preventing amyloid fibril formation, and that

variants of TTR could be associated with AD [Schwarzman et

al., Proc. Natl. Acad. Sci. USA, 91 (1994)]. Because of this

possible association, we screened for TTR mutations from 47

sporadic and 19 early-onset familial AD patients using single

strand conformation polymorphism analysis. Our results show

no correlation between TTR variants and Alzheimer's disease

in this group of patients.. 0; 0; 0.

128. Panula, P.; Aarnisalo, A. A.; Wasowicz, K. Neuropeptide FF, a

mammalian neuropeptide with multiple functions. Prog-

Neurobiol. 1996 Mar; 48(4-5): 461-87; ISSN: 0301-0082.

ENGLAND. Neuropeptide FF (NPFF) and neuropeptide AF (NPAF)

are two mammalian amidated neuropeptides which are highly

concentrated in the posterior pituitary, spinal cord,

hypothalamus and medulla. One precursor protein has been

identified in mouse, rat, bovine and human brain. The precursor

contains a single copy of both peptides, followed by a glycine

residues necessary for amidation and flanked by basic residues

necessary for processing by enzymes. In the brain, NPFF-like

immunoreactive neurons are found in the hypothalamus and

medulla. These systems may be associated with observed

effects of NPFF on memory and autonomic regulation,

respectively. A hypothalamo-pituitary pathway may be

involved in neuroendocrine regulation. This is supported by

lack of NPFF in the pituitary gland of vasopressin-deficient

Brattleboro rats. It is also possible that NPFF acts as a

hormone, as it has been detected in human plasma. The spinal

cord contains an intrinsic NPFF-ir neuron system, with cell

bodies in the dorsal horn and around the central canal. Nerve

terminals are highly concentrated in the superficial laminae of

the dorsal horn, where NPFF-immunoreactivity can be released

by, e.g., potassium and substance P. One specific high-affinity

binding site, distinct from binding sites for other peptides,

has been characterized in the rat and human brain and spinal

cord. The NPFF receptor appears to be coupled to a G-protein,

but details of the second messenger systems have not been

clarified yet. Intracerebroventricular injection of NPFF

induces a vigorous abstinence syndrome in morphine-tolerant

rats. Although clear antiopioid-like effects of NPFF on pain

have been observed, some studies have also demonstrated

long-lasting analgesic effects. These findings and the

observed increase in NPFF-immunoreactivity in the

cerebrospinal fluid during development of opiate tolerance

render NPFF an interesting and challenging target of

investigation.. 0; 0; 0; 0; 99566-27-5.

129. Paoni, N. F.; Steinmetz, H. G.; Gillett, N.; Refino, C. J.; Badillo, J. M.;

Bunting, S. An experimental model of intracranial hemorrhage

during thrombolytic therapy with t-PA. Thromb-Haemost. 1996

May; 75(5): 820-6; ISSN: 0340-6245.

GERMANY. Multiple clinical trials have proven that

thrombolytic therapy is an effective treatment for acute

myocardial infarction. Spontaneous intracranial hemorrhage

(ICH) occurs in a small percentage of patients as a result of

the treatment. The etiology of the ICH is unknown and there is

currently no established experimental model for this side

effect. A model of ICH during thrombolytic therapy has been

developed using spontaneously hypertensive rats (SHR). The

SHR were made susceptible to ICH during thrombolytic therapy

by bilateral ligation of the external jugular veins. This

procedure produced asymptomatic hemorrhagic lesions in the

brains of the animals in the hours preceding the

administration of t-PA/heparin. The incidence of ICH following

the administration of test substances was assessed by

histological examination and by measuring the red blood cell

count in a sample of cerebrospinal fluid taken from the

atlanto-occipital space. t-PA administration produced a low

frequency of ICH in this model. The incidence and severity of

ICH were dramatically increased, and significant mortality at

24h was observed, by combining heparin were administered

sequentially rather than simultaneously. Furthermore, ICHs

were observed whether the t-PA dose was administered over 4

h, 1 h, or as a double bolus 30 min apart. The potentiation of

ICH by heparin was dose dependent and proportional to the

prolongation of the aPTT. Although the precise mechanism of

ICH during thrombolytic therapy is unknown, many similarities

exist between the observations made in this model and in the

human clinical experience.. EC 3.4.-; EC 3.4.21.-; 0; 8001-27-

2; 9000-94-6; 9005-49-6.

130. Pascual Velasco, F. [Meningoencephalitis and pancreatitis caused

by the varicella virus, herpes zoster (letter)].

Meningoencefalitis y pancreatitis por el virus de la varicela

herpes zoster. Enferm-Infecc-Microbiol-Clin. 1996 Jun; 14(6):

396-7; ISSN: 0213-005X.

SPAIN. 0.

131. Pascual, J.; del Arco, C.; Romon, T.; del Olmo, E.; Castro, E.; Pazos,

A. Autoradiographic distribution of [3H]sumatriptan-binding

sites in post-mortem human brain [see comments]. Cephalalgia.

1996 Aug; 16(5): 317-22; ISSN: 0333-1024.

Note: Comment in: Cephalalgia 1996 Aug;16(5 ):287-8.

NORWAY. The anatomical distribution of [3H]sumatriptan-

binding sites was analysed in brain tissue sections from 11

subjects. Relevant concentrations of [3H]sumatriptan-binding

sites were seen in areas such as visual cortex > locus niger >

globus pallidus > layers IV-V of the frontal cortex > subiculum

> entorhinal cortex > nucleus tractus solitarius > nucleus

trigeminalis caudalis. This distribution of [3H]sumatriptan-

binding sites in the human brain shows some differences when

compared with that of 5HT1D receptors, confirming that,

besides 5HT1D, sumatriptan also binds to 5HT1F receptor

subtype. Some species differences are evident between the

distribution of [3H]sumatriptan-binding sites in the human

brain and that reported for guinea-pig and rat brains,

emphasizing that caution is needed in extrapolating

experimental data from animals to humans. Furthermore, these

data help to explain some of the therapeutic actions of

sumatriptan. The remarkable levels of binding found in areas

as nucleus tractus solitarius and nucleus trigeminalis caudalis

suggest that in migraine attacks sumatriptan could exert its

specific anti-emetic effects and, partly at least, induce

analgesia by directly acting over these brain nuclei.. 0; 0; 0; 0;

0; 103628-46-2.

132. Perlmann, P.; Perlmann, H.; Flyg, B. W.; Hagstedt, M.; Elghazali, G.;

Worku, S.; Fernandez, V.; Rutta, A. S.; Troye Blomberg, M.

Immunoglobulin E, a pathogenic factor in Plasmodium

falciparum malaria. Infect-Immun. 1997 Jan; 65(1): 116-21;

ISSN: 0019-9567.

UNITED-STATES. Most children and adults living in areas

where the endemicity of Plasmodium falciparum malaria is

high have significantly elevated levels of both total

immunoglobulin E (IgE) and IgE antimalarial antibodies in

blood. This elevation is highest in patients with cerebral

malaria, suggesting a pathogenic role for this immunoglobulin

isotype. In this study, we show that IgE elevation may also be

seen in severe malaria without cerebral involvement and

parallels an elevation of tumor necrosis factor alpha (TNF).

IgE-containing serum from malaria immune donors was added

to tissue culture plates coated with rabbit anti-human IgE

antibodies or with P. falciparum antigen. IgE-anti-IgE

complexes as well as antigen-binding IgE antibodies induced

TNF release from peripheral blood mononuclear cells (PBMC).

Nonmalaria control sera with no IgE elevation induced

significantly less of this cytokine, and the TNF-inducing

capacity of malaria sera was also strongly reduced by passing

them over anti-IgE Sepharose columns. The cells giving rise to

TNF were adherent PBMC. The release of this cytokine probably

reflects cross-linking of their low-affinity receptors for IgE

(CD23) by IgE-containing immune complexes known to give rise

to monocyte activation via the NO transduction pathway. In

line with this, adherent monocytic cells exposed to IgE

complexes displayed increased expression of CD23. As the

malaria sera contained IgG anti-IgE antibodies, such

complexes probably also play a role in the induction of TNF in

vivo. Overproduction of TNF is considered a major pathogenic

mechanism responsible for fever and tissue lesions in P.

falciparum malaria. This overproduction is generally assumed

to reflect a direct stimulation of effector cells by certain

parasite-derived toxins. Our results suggest that IgE elevation

constitutes yet another important mechanism involved in

excessive TNF induction in this disease.. 0; 0; 0; 0; 37341-29-

133. Pierpaoli, C.; Jezzard, P.; Basser, P. J.; Barnett, A.; Di Chiro, G.

Diffusion tensor MR imaging of the human brain. Radiology.

1996 Dec; 201(3): 637-48; ISSN: 0033-8419.

UNITED-STATES. PURPOSE: To assess intrinsic properties of

water diffusion in normal human brain by using quantitative

parameters derived from the diffusion tensor, D, which are

insensitive to patient orientation. MATERIALS AND METHODS:

Maps of the principal diffusivities of D, of Trace(D), and of

diffusion anisotropy indices were calculated in eight healthy

adults from 31 multisection, interleaved echo-planar

diffusion-weighted images acquired in about 25 minutes.

RESULTS: No statistically significant differences in Trace(D)

(approximately 2,100 x 10(-6) mm2/sec) were found within

normal brain parenchyma, except in the cortex, where Trace(D)

was higher. Diffusion anisotropy varied widely among

different white matter regions, reflecting differences in

fiber-tract architecture. In the corpus callosum and pyramidal

tracts, the ratio of parallel to perpendicular diffusivities was

approximately threefold higher than previously reported, and

diffusion appeared cylindrically symmetric. However, in other

white matter regions, particularly in the centrum semiovale,

diffusion anisotropy was low, and cylindrical symmetry was

not observed. Maps of parameters derived from D were also

used to segment tissues based on their diffusion properties.

CONCLUSION: A quantitative characterization of water

diffusion in anisotropic, heterogeneously oriented tissues is

clinically feasible. This should improve the neuroradiologic

assessment of a variety of gray and white matter disorders.

134. Post, S. G.; Whitehouse, P. J.; Binstock, R. H.; Bird, T. D.; Eckert, S.

K.; Farrer, L. A.; Fleck, L. M.; Gaines, A. D.; Juengst, E. T.;

Karlinsky, H.; Miles, S.; Murray, T. H.; Quaid, K. A.; Relkin, N. R.;

Roses, A. D.; St. George, Hyslop PH; Sachs, G. A.; Steinbock, B.;

Truschke, E. F.; Zinn, A. B. The clinical introduction of genetic

testing for Alzheimer disease. An ethical perspective. JAMA.

1997 Mar 12; 227(10): 832-6; ISSN: 0098-7484.

UNITED-STATES. OBJECTIVE: Primary caregivers should be

aware of recent progress in the genetics of Alzheimer disease

(AD) and of the clinical and ethical considerations raised

regarding the introduction of genetic testing for purposes of

disease prediction and susceptibility (risk) analysis in

asymptomatic individuals and diagnosis in patients who

present clinically with dementia. This statement addresses

arguments for and against clinical genetic testing.

PARTICIPANTS: The 20 participants were selected by the

investigators (S.G.P., T.H.M., A.B.Z., and P.J.W.) to achieve

balance in the areas of genetics, counseling, ethics, and public

policy, and to include leadership from related consensus

projects. The consensus group met twice in closed meetings

and carried on extensive correspondence over 2 years (1995-

1997). The project was supported by the National Human

Genome Research Institute of the National Institutes of Health.

EVIDENCE: All 4 involved chromosomes were discussed in group

meetings against a background of information from several

focus group sessions with AD-affected families. The focus

groups comprised volunteers identified by the Cleveland Area

Chapter of the Alzheimer's Disease and Related Disorders

Association and represented a variety of ethnic populations.

CONSENSUS PROCESS: The first draft was written in April

1996 by the principal investigator (S.G.P.) after the consensus

group had met twice. The draft was mailed to all consensus

group members 3 times over 6 months for extensive response

and redrafting by the principal investigator until all members

were satisfied. CONCLUSIONS: Except for autosomal dominant

early-onset families, genetic testing in asymptomatic

individuals is unwarranted. Use of APOE genetic testing as a

diagnostic adjunct in patients already presenting with

dementia may prove useful but it remains under investigation.

The premature introduction of genetic testing and possible

adverse consequences are to be avoided.. 0.

135. Preiser, W.; Weber, B.; Klos, G.; Fischer, P. A.; Doerr, H. W. Unusual

course of herpes simplex virus encephalitis after acyclovir

therapy. Infection. 1996 Sep; 24(5): 384-9; ISSN: 0300-8126.

GERMANY. This is a report on a case of herpes simplex

encephalitis (HSE) taking an unusual course after initially

successful acyclovir therapy. The etiology of HSE was proven

serologically, by repeated detection of herpes simplex virus

(HSV)-specific DNA sequences in cerebrospinal fluid (CSF)

with polymerase chain reaction (PCR) and was supported by

cerebral imaging. After both the neurological symptoms and

laboratory findings had improved initially under acyclovir

therapy, the patient's clinical condition deteriorated

accompanied by a renewed increase in CSF pleocytosis and

protein content. Nuclear magnetic resonance (NMR) imaging

confirmed the finding of bilateral, mainly temporal lesions

compatible with a diagnosis of relapsing HSE. The patient

responded well to a second cycle of antiviral therapy but

required a third treatment cycle due to renewed deterioration

later on. HSV-specific DNA sequences could not be

demonstrated in several consecutive CSF samples taken after

the first week of illness but increased inflammatory changes

typical of HSE were seen on NMR during phases of

deterioration. IgM-class antibodies against HSV were detected

in CSF 4 weeks after onset of symptoms and stayed positive

for at least 7 weeks. Reasons for the repeated deterioration

and possible explanations for the absence of HSV DNA in spite

of what could be seen as relapses are discussed.. 0; 0; 0; 0; 0;

59277-89-3.

136. Public health issues and clinical and neurological characteristics

of the new variant of Creutzfeldt-Jakob disease and other

human and animal transmissible spongiform encephalopathies:

memorandum from two WHO meetings. Bull-World-Health-

Organ. 1996; 74(5): 453-63; ISSN: 0042-9686.

SWITZERLAND. The transmissible spongiform encephalopathies

(TSEs) include bovine spongiform encephalopathy (BSE), which

was first described in 1986 in cattle in the United Kingdom,

but has occurred subsequently also in other countries, and

Creutzfeldt-Jakob disease (CJD) in humans, which is rare but

with a worldwide distribution. Recently a new variant form of

CJD, with a characteristic clinical and pathological phenotype,

has been identified in the United Kingdom in a series of 11

young patients. This Memorandum reports the findings of two

WHO Consultations. The first, held on 2-3 April 1996, issued

conclusions and recommendations on certain animal products

in order to protect the health of consumers. The second, held

on 14-16 May 1996, examined, inter alia, the findings

associated with the new variant of CJD, compared these

findings with those for other TSEs, and proposed a protocol for

the diagnosis and surveillance of CJD and related diseases.. 0.

137. Puce, A.; Allison, T.; Asgari, M.; Gore, J. C.; McCarthy, G.

Differential sensitivity of human visual cortex to faces,

letterstrings, and textures: a functional magnetic resonance

imaging study. J-Neurosci. 1996 Aug 15; 16(16): 5205-15;

ISSN: 0270-6474.

UNITED-STATES. Twelve normal subjects viewed alternating

sequences of unfamiliar faces, unpronounceable nonword

letterstrings, and textures while echoplanar functional

magnetic resonance images were acquired in seven slices

extending from the posterior margin of the splenium to near

the occipital pole. These stimuli were chosen to elicit initial

category-specific processing in extrastriate cortex while

minimizing semantic processing. Overall, faces evoked more

activation than did letterstrings. Comparing hemispheres,

faces evoked greater activation in the right than the left

hemisphere, whereas letterstrings evoked greater activation

in the left than the right hemisphere. Faces primarily

activated the fusiform gyrus bilaterally, and also activated

the right occipitotemporal and inferior occipital sulci and a

region of lateral cortex centered in the middle temporal gyrus.

Letterstrings primarily activated the left occipitotemporal

and inferior occipital sulci. Textures primarily activated

portions of the collateral sulcus. In the left hemisphere, 9 of

the 12 subjects showed a characteristic pattern in which

faces activated a discrete region of the lateral fusiform

gyrus, whereas letterstrings activated a nearby region of

cortex within the occipitotemporal and inferior occipital

sulci. These results suggest that different regions of ventral

extrastriate cortex are specialized for processing the

perceptual features of faces and letterstrings, and that these

regions are intermediate between earlier processing in striate

and peristriate cortex, and later lexical, semantic, and

associative processing in downstream cortical regions.

138. Rao, S. M.; Bandettini, P. A.; Binder, J. R.; Bobholz, J. A.; Hammeke,

T. A.; Stein, E. A.; Hyde, J. S. Relationship between finger

movement rate and functional magnetic resonance signal

change in human primary motor cortex. J-Cereb-Blood-Flow-

Metab. 1996 Nov; 16(6): 1250-4; ISSN: 0271-678X.

UNITED-STATES. Functional magnetic resonance imaging

(FMRI) is a noninvasive technique for mapping regional brain

changes in response to sensory, motor, or cognitive activation

tasks. Interpretation of these activation experiments may be

confounded by more elementary task parameters, such as

stimulus presentation or movement rates. We examined the

effect of movement rate on the FMRI response recorded from

the contralateral primary motor cortex. Four right-handed

healthy subjects performed flexion-extension movements of

digits 2-5 of the right hand at rates of 1, 2, 3, 4, or 5 Hz.

Results of this study indicated a positive linear relationship

between movement rate and FMRI signal change. Additionally,

the number of voxels demonstrating functional activity

increased significantly with faster movement rates. The

magnitude of the signal change at each movement rate

remained constant over the course of three 8-min scanning

series. These findings are similar to those of previous rate

studies of the visual and auditory system performed with

positron emission tomography (PET) and FMRI.

139. Rao, S. D.; Rao, P. D.; Peter, R. E. Growth hormone-releasing

hormone immunoreactivity in the brain, pituitary, and pineal of

the goldfish, Carassius auratus. Gen-Comp-Endocrinol. 1996

May; 102(2): 210-20; ISSN: 0016-6480.

UNITED-STATES. Using antisera directed against carp growth

hormone-releasing hormone (cGHRH), the distribution of

immunoreactive (ir) structures in the brain, pituitary, and

pineal of the goldfish, Carassius auratus, was investigated.

The antisera were produced in rabbits by administration of

cGHRH(1-44)-NH(2) followed by cGHRH(1-45)-OH for different

periods of time, both coupled to human alpha-globulins via

bisdiazotized benzidine as immunogen. Immunoreactive

perikarya were visualized in the nucleus preopticus

periventricularis (NPP), nucleus lateralis tuberis (NLT),

nucleus of the lateral lemniscus (NLL), and the pineal. The

preoptic area and area ventralis telencephali seemed to

receive innervation from the NPP cells. The fibers of the NLT

cell bodies extended caudally along the infundibular floor and

innervated the hypophysis. The processes of the NLL perikarya

extended rostrally along the lateral lemniscus, curved

ventrally along the outer margin of the glomerular nuclear

complex, and extended to the dorsal area of the lateral recess,

while issuing fascicles that branched off and fanned out to

innervate extensively the nucleus diffusus of the hypothalamic

inferior lobes and the nucleus lateralis tori; several fiber

bundles branched off and extended toward the lateral areas of

the paraventricular organ area and even into the rostral region

of the hypothalamic inferior lobes. A small percentage of the

corticotrophs of the rostral pars distalis, a few cells in the

central area of the pars intermedia (PI), and neurohypophysial

fibers in the peripheral area of the PI of the pituitary gland

had colocalization of GHRH-ir; GHRH-ir fibers in the rostral

and proximal pars distalis were sparse. It is suggested that

the GHRH-ir perikarya of the diencephalon may stimulate

growth hormone release either by modulating the activity of

somatotrophs or of other hypothalamic neurosecretory

neurons. The innervation of the hypothalamic inferior lobe by

GHRH-ir perikarya of the NLL suggests some influence on

feeding processes. Presence of GHRH in the pineal implies

involvement in some daily cyclic activity.. 9034-39-3.

140. Raymond, A. A.; Fish, D. R. EEG features of focal malformations of

cortical development. J-Clin-Neurophysiol. 1996 Nov; 13(6):

495-506; ISSN: 0736-0258.

UNITED-STATES. Recent advances in neuroimaging have

allowed the detection and characterization of focal

malformations of cortical developmental in a significant

proportion of patients with epilepsy, many of whom were

previously labelled as cryptogenic, allowing a better

description of the associated electroencephalogram (EEG)

features. Alpha activity is usually preserved, although

superficial gyral abnormalities are often associated with

overlying localized polymorphic delta activity, and

occasionally abnormal fast activity. Most affected patients

with epilepsy show interictal spikes. These are often broadly

concordant with the structural abnormality but may show a

wider anatomic distribution and be multifocal, or occasionally

appear only in anatomically distant sites. In many patients the

spikes are frequent and sometimes they occur continuously or

in long trains. EEG findings are often stable over time, but

some patients only show the development of slow wave

changes or interictal spikes when followed serially for

several years. A small proportion of patients with focal

malformations of cortical development have EEG features

mimicking idiopathic generalized epilepsy, and occasionally

patients exhibit continuous generalized spike and slow wave

activity in sleep. Electrocorticography studies confirm the

often widespread nature of interictal spiking, but may also

show highly epileptogenic patterns recorded directly from

dysplastic cortex. The intrinsic epileptogenicity of areas of

cortical developmental abnormalities has also been

demonstrated by chronic intracranial studies and in vitro

recordings of slices obtained from resected human dysplastic

cortex. In this regard such developmental abnormalities are

fundamentally different from acquired lesions such as

tumors/vascular anomalies that usually exert their effects

through changes in adjacent cortex.

141. Retamal, C.; Zulantay, I.; Sariego, H.; Melo, R.; Apt, W. [Evaluation

of ELISA and counterimmunoelectrophoresis in diagnosis of

human neurocysticercosis in Chile]. Evaluacion de ELISA y

contrainmunoelectroforesis en el diagnostico de la

neurocisticercosis humana en Chile. Rev-Med-Chil. 1995 Dec;

123(12): 1461-6; ISSN: 0034-9887.

CHILE. The aim of this work was to assess the diagnostic

accuracy for neurocysticercosis, of ELISA and

counterimmunoelectrophoresis techniques, in sera and

cerebrospinal fluid. Two hundred eight serum samples (47

coming from patients with confirmed cysticercosis) and 87

cerebrospinal fluid samples (27 coming from patients with

confirmed cysticercosis) were analyzed. A crude and

standardized extract of swine muscle cysticercus cellulose

was used as antigen. ELISA and counter immunoelectrophoresis

had a 100% specificity in cerebrospinal fluid. In sera,

counterimmunoelectrophoresis had a 94.1% specificity. In sera

and cerebrospinal fluid, ELISA had a 85.1% sensitivity. Cross

reactions were observed in sera of patients with confirmed

hydatidosis. Thus, the high specificity of both techniques in

cerebrospinal fluid is probably due to the low incidence of

cerebral hydatidosis in Chile. It is concluded that for the

diagnosis of neurocysticercosis, antibodies against

cysticercus cellulosae must be sought paralelly in serum and

cerebrospinal fluid using ELISA and

counterimmunoelectrophoresis.. 0; 0.

142. Rho, M. B.; Wesselingh, S.; Glass, J. D.; McArthur, J. C.; Choi, S.;

Griffin, J.; Tyor, W. R. A potential role for interferon-alpha in

the pathogenesis of HIV-associated dementia. Brain-Behav-

Immun. 1995 Dec; 9(4): 366-77; ISSN: 0889-1591.

UNITED-STATES. Previous studies in patients receiving

interferon-alpha (IFN-alpha) therapy and patients with

systemic lupus erythematosus have demonstrated that

elevated cerebrospinal fluid (CSF) levels of IFN-alpha are

associated with cognitive dysfunction. We measured IFN-alpha

levels in CSF and blood by ELISA in human immunodeficiency

virus (HIV)-positive patients with (n = 21) and without (n =

23) dementia and HIV-negative controls (n = 48). IFN-alpha

was significantly elevated in the CSF of HIV-positive patients

with dementia compared to those without dementia and

controls. An increasing amount of IFN-alpha in the CSF was

correlated with the clinical parameter of increasing Memorial

Sloan Kettering scores; although these correlations were not

statistically significant, they further suggest an association

of increased CSF IFN-alpha with neurocognitive dysfunction in

AIDS. Immunocytochemical staining of brains demonstrated

IFN-alpha-positive macrophages and astrocytes in frontal

cortex and white matter and IFN-alpha mRNA was detected by

reverse transcriptase-polymerase chain reaction, further

indicating that IFN-alpha is made by cells within the brain and

suggesting that the significant increases of IFN-alpha protein

found in the CSF of patients with HIV-associated dementia

complex are derived from intrinsic brain cells such as

macrophages and astrocytes. Increased local production of

IFN-alpha during HIV infection may contribute directly or

indirectly to the pathogenesis of HIV-associated dementia.. 0;

0; 0.

143. Rihs, J. D.; Padhye, A. A.; Good, C. B. Brain abscess caused by

Schizophyllum commune: an emerging basidiomycete pathogen.

J-Clin-Microbiol. 1996 Jul; 34(7): 1628-32; ISSN: 0095-1137.

UNITED-STATES. Despite the worldwide distribution and

prevalence of Schizophyllum commune, an emerging

basidiomycetous pathogen, human infections occur only rarely.

We describe the first well-documented pulmonary infection

caused by S. commune which disseminated to the brain of a

58-year-old patient undergoing empiric corticosteroid

therapy. Magnetic resonance imaging scans revealed ring-

enhancing masses. Histologic examination of biopsy tissue

from lungs and brain showed hyaline, septate, branched hyphae

with clamp connections. Cultures of the lung tissue grew S.

commune, which produced numerous, characteristic

flabelliform and medusoid fruiting bodies on Czapek's agar.

The isolate was susceptible to amphotericin B (MIC, < 0.03

microgram/ml) and fluconazole (MIC, 8 micrograms/ml).

Despite treatment with antifungal and antibacterial agents,

the patient developed progressive pulmonary failure and

bacterial sepsis and died.. 0.

144. Rodhain, F. [Recent data on the epidemiology of Japanese

encephalitis]. Donnees recentes sur l'epidemiologie de

l'encephalite japonaise. Bull-Acad-Natl-Med. 1996 Jun; 180(6):

1325-37; discussion 1338-40; ISSN: 0001-4079.

FRANCE. Japanese encephalitis is an arbovirosis the incidence

and geographic distribution of which are increasing in rural

areas of tropical and temperate Asia. A total of about 45,000

to 50,000 clinical cases occur annually. The Flavivirus

responsible for the disease shows birds as usual hosts, and

Culex mosquitoes as vectors. After a first amplification cycle

in birds, the virus can be transmitted to domestic pigs, then to

man. This scheme, however, shows large variations in the

different regions, according to the climate which determines

the dynamics of mosquito and bird populations, and to the

ways of life of human populations, particularly for the rice-

growing technics and pig breeding. The epidemiologists

schematically distinguish tropical endemic areas, subtropical

endemic-epidemic zones, and temperate epidemic zones.

However, our knowledge on the epidemiology of Japanese

encephalitis carries many incompletely understood aspects,

for instance the reasons of the actual geographic distribution

of the disease, or the mechanisms for persistence of the virus

between epidemics. Furthermore, these epidemiological

situations are changing with time, particularly with the-

development of the new agrosystems linked with demographic

increase, while recent technics of genomic analysis allow the

recognition of several viral genotypes. The prevention of

Japanese encephalitis presently involves vector control,

vaccination and, in some cases, particular modifications of

environment. Each of these measures shows proper logistic,

technical or financial difficulties, which often prevent their

generalized use. However, one can observe that, in the

countries where vaccination is systematically carried out, the

incidence of the disease seems considerably decreasing, while

elsewhere it shows a tendency to increase. The main

difficulties lie in the high cost of the vaccine and in the

weight of immunization scheme, which make uneasy its

integration in the Expanded Vaccination Programme. For these

reasons, the virologists are looking for other vaccine types,

particularly recombinant vaccines relying on obtaining, by

genetical manipulation, envelop proteins with protection

effect. Finally, remains the question of immunization of

travellers and expatriate people. It seems desirable to

recommand this vaccine only to the really exposed persons;

this means persons performing a rather long stay in a rural

area of an endemo-epidemic region, or during the season of

transmission in an epidemic region. However, the risk cannot

be completely absent, and it is necessary to draw attention to

other methods aiming at decreasing man-vector contact.

145. Roland, P. E.; Zilles, K. Functions and structures of the motor

cortices in humans. Curr-Opin-Neurobiol. 1996 Dec; 6(6): 773-

81; ISSN: 0959-4388.

ENGLAND. Humans and non-human primates have several motor

areas. Exactly how many is a matter of current debate. A

proper parcellation of motor areas must be based on correlated

structural and functional differences. Recent studies indicate

that the primary motor cortex may be, in reality, two areas

(4a and 4p). Similarly, there are undoubtedly two or more

cingulate motor areas and perhaps two supplementary motor

areas. The homologies between human and monkey brains are

striking in some cases, making monkey models of human motor

cortices attractive. The doctrine of a strict 'homuncular'

somatotopical organization of motor areas will have to be

abandoned. The engagement of motor areas in different types

of voluntary seems merely a matter of degree of activation

rather than exclusive specific contributions.

146. Ross, B. D.; Danielsen, E. R.; Bluml, S. Proton magnetic resonance

spectroscopy: the new gold standard for diagnosis of clinical

and subclinical hepatic encephalopathy? Dig-Dis. 1996; 14

Suppl 1: 30-9; ISSN: 0257-2753.

SWITZERLAND. Human hepatic encephalopathy (HE) is

identified by a new noninvasive test, proton magnetic

resonance spectroscopy (1H MRS) applied to the brain in a few

minutes. Chemical changes identified by 1H MRS are elevated

glutamine, decreased choline and decreased myoinositol. The

specific association with HE is proven by clinical studies in

patients with cirrhosis, overt and subclinical HE, by the

appearance of the same changes after transjugular

intrahepatic portasystemic shunt, and by their complete

reversal by liver transplantation. The importance of the new

marker, myoinositol, may lie in its role as an osmolyte

regulating cell volume in the astrocytes. Other roles are also

postulated. Progress in the management of both HE and

subclinical hepatic encephalopathy may depend upon finding

means, short of liver transplantation, which will restore

cerebral choline and myoinositol. The finding of identical

changes in experimental animals simplifies the search.. 0;

1333-74-0; 62-49-7; 6899-04-3; 6917-35-7.

147. Rostrup, E.; Larsson, H. B.; Toft, P. B.; Garde, K.; Ring, P. B.;

Henriksen, O. Susceptibility contrast imaging of CO2-induced

changes in the blood volume of the human brain. Acta-Radiol.

1996 Sep; 37(5): 813-22; ISSN: 0284-1851.

DENMARK. PURPOSE: To investigate changes in the regional

cerebral blood volume (rCBV) in human subjects during rest

and hypercapnia by MR imaging, and to compare the results

from contrast-enhanced and noncontrast-enhanced

susceptibility-weighted imaging. MATERIAL AND METHODS:

Five healthy volunteers (aged 24-29 years) were studied

during inhalation of atmospheric air and 7% CO2. A bolus

injection of Gd-DTPA was given during the acquisition of a

series of susceptibility-weighted, fast gradient echo images

(TR/TE = 27/22 ms). The images were converted to delta R2*

maps, and CBV was calculated pixelwise by fitting a gamma-

variate function to the data. The tissue concentration vs time

curves were deconvoluted using an input function obtained by

arterial sampling. RESULTS: The ratio of gray to white matter

CBV (1.9-2.5) as well as the fractional increase in rCBV during

hypercapnia (about 30%) was found to be in accordance with

results obtained by other methods. Noncontrast functional MR

(fMR) imaging showed signal increases in gray matter, but also

inconsistent changes in some white matter regions.

CONCLUSION: In this experiment, contrast-enhanced imaging

seemed to show a somewhat higher sensitivity towards

changes in cerebral hemodynamics than noncontrast-enhanced

imaging. The results of the deconvolution analysis suggested

that perfusion calculation by conventional tracer kinetic

methods may be impracticable because of nonlinear effects in

contrast-enhanced MR imaging.. 0; 0; 124-38-9; 67-43-6;

80529-93-7.

148. Sadile, A. G.; Pellicano, M. P.; Sagvolden, T.; Sergeant, J. A. NMDA

and non-NMDA sensitive [L-3H]glutamate receptor binding in

the brain of the Naples high- and low-excitability rats: an

autoradiographic study. Behav-Brain-Res. 1996 Aug; 78(2):

163-74; ISSN: 0166-4328.

NETHERLANDS. The Naples high-excitability (NHE) and low-

excitability (NLE) rat lines, selectively bred for high and low

activity in a Lat maze, respectively, are used as an animal

model in the study of hippocampal functions. The aim of this

study was to investigate the anatomical distribution of N-

methyl-D-aspartate (NMDA) and non-NMDA sensitive

[3H]glutamate receptor binding by quantitative

autoradiography in the brain of the NHE and NLE rats with a

randomly bred line (NRB) as controls. Twenty-micron-thick

cryostat sagittal sections were incubated at 4 degrees C with

150 nM [L-3H]glutamate alone or in the presence of 100

microM NMDA or 2.5 microM quisqualate (QA). Non-specific

binding was determined in the presence of 1 mM of non-labeled

glutamate. The sections were exposed to tritium-sensitive

films for 3 weeks at 4 degrees C. Quantitative analysis

revealed: (1) higher levels of total binding in NHE than in NRB

and NLE rats in all areas but the cerebellum; (2) fewer binding

sites for both NMDA and QA receptors and larger binding sites

for QA receptors in the hippocampus of NLE and NHE rats,

respectively; (3) a positive correlation between total binding

sites and activity level in a Lat maze in all areas, except the

cerebellar molecular layer with NLE < NHE, which was due to

differential contribution from NMDA and non-NMDA types.

Thus, the brain of the NHE rats shows an imbalance between

NMDA and non-NMDA sensitive [L-3H]glutamate receptors.. 0;

0; 0; 52809-07-1; 6384-92-5.

149. Sande, R.; Tysnes, O. B. [A new variant of Creutzfeldt-Jakob

disease. Do we want development of a new epidemic?]. Ein ny

variant av Creutzfeldt-Jakobs sjukdom. Vil vi sja utvikling av

ein epidemi? Tidsskr-Nor-Laegeforen. 1997 Jan 30; 117(3):

384-8; ISSN: 0029-2001.

NORWAY. Human spongiform encephalopathies have been

receiving a lot of attention lately, because of a new variant of

Creutzfeldt-Jakob disease and its possible connection to

bovine spongiform encephalopathy which has reached epidemic

proportions in Great Britain during the last ten years. Four

different human spongiform encephalopathies have been

described, the most common being Creutzfeldt-Jakob disease,

which can occur in a sporadic, familial or transmissible form.

The infectious agent is mainly, possibly solely, composed of a

pathogenous isoform of a normal membrane-bound

glycoprotein, called a prion. In animals, spongiform

encephalopathies occur most frequently in sheep, as scrapie,

and in cattle, as bovine spongiform encephalopathy, also known

as mad cow disease. There is substantial evidence to suggest

that this disease in cattle is the source of the new variant of

Creutzfeldt-Jakob disease, although this has yet to be proven.

An important question is whether the cases of the new variant

of Creutzfeldt-Jakob disease registered so far are the start of

an epidemic, as in the case of bovine spongiform

encephalopathy.

150. Sandyk, R. Effect of weak electromagnetic fields on body image

perception in patients with multiple sclerosis. Int-J-Neurosci.

1996 Jul; 86(1-2): 79-85; ISSN: 0020-7454.

ENGLAND. Cerebellar ataxia is one of the most disabling

symptoms of multiple sclerosis (MS) and also one of the least

responsive to pharmacotherapy. However, cerebellar symptoms

often improve dramatically in MS patients by brief,

extracerebral applications of picotesla flux electromagnetic

fields (EMFs). This report concerns two MS patients with

chronic disabling ataxia who experienced rapid improvement in

gait and balance after receiving a series of treatments with

EMFs. To assess whether improvement in cerebellar gait is

accompanied by changes in body image perception, a parietal

lobe function, both patients were administered the Human

Figure Drawing Test before and after a series of brief

treatments with EMFs. Prior to application of EMFs these

patients' free drawings of a person showed a figure with a

wide-based stance characteristic of cerebellar ataxia. After

receiving a series of EMFs treatments both patients

demonstrated a change in body image perception with the

drawings of the human figure showing a normal stance. These

findings demonstrate that in MS improvement in cerebellar

symptoms by pulsed applications of picotesla EMFs is

associated with changes in the body image.

151. Saris, S. Multidisciplinary approach to malignant gliomas. Med-

Health-R-I. 1996 Jun; 79(6): 210-3; ISSN: 1086-5462.

UNITED-STATES. Primary malignant brain tumors are among

the most difficult human malignancies to manage. Other

common tumors such as in the lung or breast generally can be

cured if caught at an early stage. A 2 cm adenocarcinoma in

the peripheral lung field without mediastinal or systemic

metastasis can be cured. A small breast carcinoma which has

not invaded into the regional lymph nodes can generally be

removed with the expectation of permanent control. However,

a 1 cm glioblastoma in the anterior right frontal lobe, even

with gross total resection and maximum adjunctive radiation,

will recur and cause death within a year or two. There is no

realistic possibility of cure or even long-term survival. These

patients pose unusual management problems. They require

different medications such as anticonvulsants and steroids.

There are neurocognitive problems and the quality of life is

usually worse than for the other common malignancies. They

require a multidisciplinary approach with health care

providers skilled in a variety of disciplines. Malignant gliomas

have two components. There is the main bulk of the tumor (the

ring enhancing portion seen on the MRI) and the infiltrating

portion than cannot be seen by any imaging method. Local

control has improved over the past ten years, but control of

the infiltrating portion is still lacking. It is likely that some

form of biologic approach will be needed to seek out and kill

these infiltrating cells that travel with such ease within the

white matter tracts of the brain. Perhaps selective delivery of

self-destruct genes to these cells will be possible. Perhaps

the search and destroy potential of the immune system can be

harnessed. If so, this incurable cancer may some day be

brought under control. The effort involved will be extensive

both in the laboratory and in the clinic.

152. Sasseville, V. G.; Smith, M. M.; Mackay, C. R.; Pauley, D. R.;

Mansfield, K. G.; Ringler, D. J.; Lackner, A. A. Chemokine

expression in simian immunodeficiency virus-induced AIDS

encephalitis. Am-J-Pathol. 1996 Nov; 149(5): 1459-67; ISSN:

0002-9440.

UNITED-STATES. The pathogenesis of neurological dysfunction

associated with human immunodeficiency (HIV)-1 infection is

uncertain. However, the presence of macrophage infiltrates in

the central nervous system is a key feature of HIV

encephalitis and is correlated with HIV-associated dementia.

Moreover, it has been demonstrated that HIV-infected

monocyte/macrophages can produce toxic substances that may

play a critical role in the development of HIV-associated

dementia. However, the exact mechanisms responsible for HIV

infection and leukocyte recruitment to the central nervous

system remain speculative. Similar to HIV-infected patients,

simian immunodeficiency virus (SIV)-infected macaque

monkeys develop immunosuppression and acquired immune

deficiency syndrome (AIDS)-related inflammatory disorders,

including AIDS encephalitis. In this study, we demonstrate

that encephalitic brain from SIV-infected animals has

elevated immunohistochemical expression of the C-C

chemokines, macrophage inflammatory protein-1 alpha and -

beta, RANTES, and monocyte chemotactic protein-3, and the C-

X-C chemokine interferon-inducible protein-10. These findings

suggest that one or all of of these chemokines could be

involved in leukocyte recruitment to the brain in SIV-infected

macaque monkeys.. 0; 0; 0; 0; 0; 0; 0.

153. Schabel, A.; Konig, A. L.; Brand, U.; Schnaidt, M.; Sugg, U. [Severe

neonatal alloimmune thrombocytopenia with delayed antibody

detection]. Schwere neonatale Alloimmunthrombozytopenie

mit verzogertem Antikorpernachweis. Beitr-Infusionsther-

Transfusionsmed. 1996; 33: 156-9; ISSN: 1023-2028.

SWITZERLAND. Neonatal alloimmune thrombocytopenia (NAIT)

is caused by maternal immunisation against a paternal antigen

on fetal platelets. The antigen involved in the majority of

cases is HPA-1 a (PIA1). Usually circulating platelet

alloantibodies are detectable in the mother. In this report, we

present a thrombocytopenic newborn with severe hemorrhagic

diathesis due to materno-fetal HPA-1 a (PIA1)

incompatibility. Platelet antibodies could initially not be

demonstrated in the mother's serum but became detectable

after four weeks. Because of the severe and protracted course

of the disease, repeated platelet substitution was necessary

throughout the first two months of life.. 0; 0.

154. Schlingemann, R. O.; Bruinenberg, M.; Wertheim, van Dillen P.;

Feron, E. Twenty years' delay of fellow eye involvement in

herpes simplex virus type 2-associated bilateral acute retinal

necrosis syndrome. Am-J-Ophthalmol. 1996 Dec; 122(6): 891-

2; ISSN: 0002-9394.

UNITED-STATES. PURPOSE: To describe a case of acute retinal

necrosis with concurrent encephalitis and determine the

causative virus. The patient had a history of presumed acute

retinal necrosis in the left eye at the age of 8 years and

recurrent genital herpes. METHODS: Diagnostic anterior

chamber puncture of the eye and lumbar puncture for

laboratory analysis. RESULTS: Polymerase chain reaction

identified herpes simplex virus type 2 in the eye, and local

antibody production to herpes simplex virus was demonstrated

in the aqueous of this eye and in the cerebrospinal fluid.

CONCLUSION: Herpes simplex virus type 2 may cause bilateral

acute retinal necrosis with long delay of fellow eye

involvement and concurrent encephalitis.. 0; 0; 0; 59277-89-

155. Schupp, W. [Current aspects of neurologic and neurosurgical

rehabilitation in ambulatory medicine]. Aktuelle Aspekte der

neurologischen und neurochirurgischen Rehabilitation fur die

ambulante Medizin. Z-Arztl-Fortbild-Jena. 1996 Oct; 90(6):

501-9; ISSN: 0044-2178.

GERMANY. Nearly all neurological and neurosurgical diseases

can cause lasting disabilities. Therefore, neurorehabilitation

is needed. The German Pension Insurance Association has

developed a concept of phases working as a chain of treatment,

rehabilitation and care. This was confirmed as the one official

system by the German Federal Society for Rehabilitation

consisting of all social insurances and wellfare sponsors. The

goals and tasks of each phase are defined by the functional

status of the patients and their requirements for recovery. The

costs are mostly determined by the social health or the social

pension insurances. Different professions (physicians, nurses,

physiotherapists, occupational therapists, speech therapists,

(neuro-)psychologists, social workers) have to cooperate as a

"therapeutic team" to improve the patient's impairments,

disabilities and handicaps and to make full use of their

individual resources of recovery. Only this can be the basis for

valid prognostic decisions. In the long term treatment and care

of the general practitioner, stroke patients are the most

important group. Special problems are seen after traumatic

brain injuries. Other relevant diagnoses are Parkinson's

syndrome, multiple sclerosis, diseases and injuries of the

spinal cord or the peripheral nervous system. In many patients,

special aids have to be prescribed for several aspects of

human living.

156. Schwarzman, A. L.; Goldgaber, D. Interaction of transthyretin with

amyloid beta-protein: binding and inhibition of amyloid

formation. Ciba-Found-Symp. 1996; 199: 146-60; discussion

160-4; ISSN: 0300-5208.

NETHERLANDS. Aggregated amyloid beta-protein (A beta) is a

key component of the amyloid depositions found in the brains

of patients with Alzheimer's disease. In contrast, in

cerebrospinal fluid (CSF), A beta is found in a soluble form.

The analysis of complexes of A beta with CSF proteins in a KBr

gradient revealed an association of A beta only with free

proteins and not with lipoprotein particles. Transthyretin

(TTR), a second major CSF protein, formed SDS-stable

complexes with A beta and significantly decreased the rate of

A beta fibril formation. In physiological buffers and CSF, TTR

exclusively decreased the level of A beta pentamers.

Endogenous TTR-A beta complexes were detected in human CSF

by immunoprecipitation. Using site-directed mutagenesis and

computer-assisted modelling, we identified amino acid

residues on the surface of the TTR monomer that interact with

A beta. Specific TTR immunoreactivity was detected in

multiple cortical neurons and astrocytes in the human brain.

We propose that A beta binding proteins play a key role in the

modulation of A beta aggregation and normally prevent amyloid

formation in biological fluids and in the brain.. 0; 0; 0; 0.

157. Seeman, P.; Corbett, R.; Nam, D.; Van, Tol HH. Dopamine and

serotonin receptors: amino acid sequences, and clinical role in

neuroleptic parkinsonism. Jpn-J-Pharmacol. 1996 Jul; 71(3):

187-204; ISSN: 0021-5198.

JAPAN. This review summarizes the amino acid sequences of

the human dopamine and serotonin receptors and their human

variants. The review also examines the receptor basis of the

atypical antipsychotic drugs that elicit less parkinsonism than

the typical antipsychotics. Because the dissociation constant

of a drug varies with the radioligand, the dissociation

constants of many neuroleptics are here summarized for the

dopamine D2-, D4- and serotonin S2A-receptors using

different radioligands. Radioligands of low solubility in the

membrane (having low tissue/buffer partition) result in lower

values for the neuroleptic dissociation constants, compared to

radioligands of high membrane solubility. Such studies yield

the intrinsic K value for a neuroleptic in the absence of a

competing ligand. Clozapine, for example, has an intrinsic K

value of 1.6 nM at the D4-receptor, in agreement with the

value of 1.6 nM when directly measured with [3H]clozapine at

D4. However, because clozapine competes with endogenous

dopamine, the in vivo clozapine concentration to occupy 75% of

the dopamine D4-receptors is derived to be approximately 13

nM. This agrees with the value of 12 to 20 nM in the plasma

water (or spinal fluid) observed in treated patients. Moreover,

in L-DOPA psychosis (in Parkinson's disease), the clozapine

concentration for 75% blockade of D4 is predicted to be

approximately 3 nM. This agrees with the value of

approximately 1.2 nM observed by Meltzer et al. in plasma

water (Neuropsychopharmacology, 12, 39-45 (1995)). This

analysis supports the concept and practical value of the

intrinsic K values. Some atypical neuroleptics (remoxipride,

clozapine, perlapine, seroquel and melperone) have high

intrinsic K values (ranging from 30 to 88 nM) at the D2-

receptor, making them displaceable by high levels of

endogenous dopamine in the caudate/putamen. In contrast,

however, typical neuroleptics (i.e., those that typically cause

parkinsonism) have intrinsic K values of 0.3 to 6 nM, making

them less displaceable by endogenous dopamine. A relationship

exists between the neuroleptic doses for rat catalepsy and the

D2/D4 ratio of the intrinsic K values. Thus, the atypical

neuroleptics appear to fall into two groups, those that bind

loosely to D2 and those that are selective at D4.. 0; 0; 0;

5786-21-0.

158. Seidman, D. S.; Nass, D.; Mendelson, E.; Shehtman, I.; Mashiach, S.;

Achiron, R. Prenatal ultrasonographic diagnosis of fetal

hydrocephalus due to infection with parainfluenza virus type 3.

Ultrasound-Obstet-Gynecol. 1996 Jan; 7(1): 52-4; ISSN: 0960-

7692.

ENGLAND. Parainfluenza virus type 3 is one of the most

common causes of respiratory infection in infants. No

complications of pregnancy or fetal anomalies have been

reported in association with parainfluenza virus infection. A

pregnancy was terminated at 22 weeks' gestation due to

ultrasonographic diagnosis of hydrocephalus. Pathological

examination was consistent with viral encephalitis,

ventriculitis and pneumonia. Serological investigation

demonstrated a significant rise in maternal antibody titers for

parainfluenza virus type 3. Parainfluenza virus type 3 may be

associated with severe fetal infection in the first half of

pregnancy. Serological studies for this virus should be

considered in cases of fetal hydrocephalus.. 0.

159. Sekhon, L. H.; Morgan, M. K.; Spence, I. Normal perfusion pressure

breakthrough: the role of capillaries. J-Neurosurg. 1997 Mar;

86(3): 519-24; ISSN: 0022-3085.

UNITED-STATES. Excision of human cerebral arteriovenous

malformations (AVMs) can be complicated by postoperative

edema and hemorrhage in adjacent brain tissue, despite the

complete excision of the malformation. Various theories have

purported to explain the hemodynamic basis for this

predisposition, including disordered autoregulation causing

"normal perfusion pressure breakthrough" and obstruction of

venous drainage leading to "occlusive hyperemia." This study

did not evaluate the arterial or venous circulations in this

scenario, but rather examined the capillaries in adjacent brain

parenchyma for any structural deficiencies that would

predispose the brain to the postoperative formation of edema

and hemorrhage. Arteriovenous fistulas (AVFs) were created

surgically in the necks of 10 male Sprague-Dawley rats, which

caused chronic cerebral hypoperfusion with a reduction in

cerebral blood flow of between 25% and 50%. Ten age-matched

animals were used as controls. Twenty-six weeks after AVF

formation the animals were killed and perfusion fixed. Their

brain tissue was prepared for light microscopic studies by

staining for glial fibrillary acidic protein or for transmission

electron microscopy. In the CA1 pyramidal cell region of the

hippocampus, it was found that in the animals with AVFs there

was increased capillary density and absent astrocytic foot

processes in some of these vessels. It was concluded that

these vessels had developed as a result of neovascularization

in response to chronic cerebral ischemia and that their

anatomical configuration made them prone to mechanical

weakness and instability following the increase in perfusion

pressure that occurs in adjacent brain parenchyma after AVM

excision. The authors believe that this study pinpoints a

structural accompaniment to the hemodynamic changes that

occur in brain tissue in the vicinity of cerebral AVMs that

predispose these areas to the formation of edema and

hemorrhage after AVM excision.. 0; 0.

160. Shah, S. S.; Zimmerman, R. A.; Rorke, L. B.; Vezina, L. G.

Cerebrovascular complications of HIV in children. AJNR-Am-J-

Neuroradiol. 1996 Nov; 17(10): 1913-7; ISSN: 0195-6108.

UNITED-STATES. Two uncommon but important

cerebrovascular manifestations of human immunodeficiency

virus (HIV) infection in children are arteritis with formation

of fusiform aneurysms and arterial sclerosis with vascular

occlusion. We studied the CT and MR imaging features of HIV in

two girls and one boy (9 to 18 years old) and compared them

with autopsy findings in two patients. One of the children had

findings consistent with small areas of subacute infarction

and the other two had fusiform dilatation of the major vessels

of the circle of Willis. The ischemic lesions and arteriopathy

were confirmed at autopsy. In one patient, an incidental B-cell

lymphoma (not visible on the imaging studies) was diagnosed.

161. Shannon, K. M. Chorea. Curr-Opin-Neurol. 1996 Aug; 9(4): 298-302;

ISSN: 1350-7540.

UNITED-STATES. The Huntington's disease mutation and its

protein product are widely expressed in the brain, although the

link to presumed excitotoxic damage is unknown. The

availability of the genetic test increased the study of

preclinical changes in the disease and the identification of

more rare choreic illnesses. Other types of transient or

permanent basal ganglia dysfunction might cause chorea.

162. Shoshan, Y.; Siegal, T. Control of vasogenic edema in a brain tumor

model: comparison between dexamethasone and superoxide

dismutase. Neurosurgery. 1996 Dec; 39(6): 1206-13;

discussion 1213-4; ISSN: 0148-396X.

UNITED-STATES. OBJECTIVE: The production of prostaglandin

(PG) within brain tumors probably generates excessive

amounts of oxygen free radicals that may disrupt microvessel

permeability within the tumor and in the adjacent brain. We

evaluated the effect of systemic therapy with recombinant

human manganese-superoxide dismutase (r-hMnSOD) and with

dexamethasone on the vascular permeability (VP) of a brain

tumor and the adjacent brain. Treatment effect was also

evaluated in control animals subjected to mild penetration

injury. METHODS: Fischer rats were injected stereotactically

with either 10(5) cells of malignant sarcoma or with vehicle

into the right parietal hemisphere. Nine days later, the animals

were treated with r-hMnSOD (50 mg/kg of body weight every

12 h [one intravenous, then two intraperitoneal injections];

serum levels, 1100-1800 micrograms/ml), dexamethasone (2

mg/kg every 12 h [one intravenous, then two intraperitoneal

injections]), or vehicle and were killed after 30 hours for

evaluation of VP and PG production. RESULTS: The VP was

markedly increased within the tumor (P < 0.001), in the brain

adjacent to it, and in the vehicle injection site. The VP of the

normal brain was unaffected by r-hMnSOD or dexamethasone

treatment, unlike the VP in the tumor, the adjacent brain, and

the injection sites of control animals, where it was reduced

by 50, 54, and 23%, respectively (P < 0.04), for r-hMnSOD and

50, 41, and 71%, respectively (P < 0.05), for dexamethasone. A

one- to threefold increase in synthesis of thromboxane and

PGE2 was measured within the tumor, the adjacent brain, and

the injection sites of control animals (P < 0.0001). Treatment

with r-hMnSOD had no effect on tumor PG production, but it

reduced the synthesis in the brain tissue adjacent to the tumor

and in traumatized control animals (P < 0.04).

Immunohistochemical evaluation revealed vascular

proliferation with abnormal basal membrane, atypical

astrocytes, and large numbers of reactive macrophages

present in the adjacent brain and at the injection sites of

control animals but not within the tumor mass. CONCLUSION:

Oxygen free radicals probably enhance vasogenic brain edema

resulting from tumor and penetration injury. The edema can be

attenuated by systemic r-hMnSOD therapy, which has been

proven to be as effective as steroid treatment. An

inflammatory response may account for oxygen free radical

production in brain tissue adjacent to the tumor and at the

injection site of vehicle solution, but other mechanisms

probably generate oxygen free radicals within the tumor mass..

EC 1.15.1.1; 0; 0; 0; 50-02-2.

163. Smith, D. V.; Liu, H.; Vogt, M. B. Responses of gustatory cells in

the nucleus of the solitary tract of the hamster after NaCl or

amiloride adaptation. J-Neurophysiol. 1996 Jul; 76(1): 47-58;

ISSN: 0022-3077.

UNITED-STATES. 1. The responses of single nucleus of the

solitary tract (NST) neurons in the hamster were recorded to

an array of Na+ and non-Na+ stimuli under each of three

adaptation conditions: distilled H2O, 0.032 M NaCl, and 10

microM amiloride. Each adapting solution flowed for 60 s

before delivery of one of seven test stimuli: 0.032 M NaCl,

NaNO3, and Na-gluconate, 0.1 M KCl and sucrose, 1 mM HCl, and

3 mM quinine hydrochloride (QHCl). Stimuli were dissolved in

distilled H2O (H2O and NaCl adaptation conditions) or 10

microM amiloride (amiloride adaptation condition). 2. Both

amiloride treatment and NaCl adaptation reduced responses to

the Na+ stimuli. The effects of NaCl adaptation were generally

greater than those of amiloride, and the responses to the Na+

salts were reduced by NaCl adaptation in every cell that

responded to NaCl, regardless of its best-stimulus

classification. Amiloride treatment suppressed the responses

to Na+ salts with larger anions (NaNO3 and Na-gluconate) more

than the response to NaCl. 3. Unlike amiloride treatment, NaCl

adaptation also reduced responses to several non-Na+ stimuli

(KCl, HCl, and QHCl). This effect occurred primarily in the

NaCl-best neurons that were most highly responsive to NaCl

and that showed a postexcitatory suppression after NaCl. This

suppression has been observed in recordings from the chorda

tympani nerve in both rats and hamsters and in taste receptor

cell responses recorded in situ in the rat. If it is a receptor

phenomenon, these data would imply that some NaCl-sensitive

receptor cells are also responsive to these non-Na+

electrolytes. 4. The effects of amiloride on the responses to

Na+ stimuli were not limited to NaCl-best neurons, but

occurred in sucrose-best cells as well. These results suggest

that the sucrose-best cells in the NST receive converging

input from sucrose- and NaCl-best chorda tympani fibers,

because there is little Na+ sensitivity in the peripheral

sucrose-best fibers and the amiloride sensitivity is restricted

to NaCl-best chorda tympani fibers. The responses to NaCl in

the few HCl- and QHCl-best NST neurons were not affected by

amiloride. 5. Rinsing the tongue with amiloride for 60 s

resulted in a reduction in the baseline response rate of NST

cells. This effect occurred primarily in NaCl- and sucrose-best

NST neurons and implies that much of the spontaneous activity

in these brain stem cells arises from amiloride-sensitive

channel activity in the peripheral receptor cells. 6. The results

of human psychophysical studies show very different effects

of NaCl adaptation and amiloride treatment. Adaptation to NaCl

produces a robust and specific reduction in the saltiness of all

salts. The present results show that NaCl adaptation reduces

the responses of all cells sensitive to NaCl. Treatment of the

human tongue with amiloride produces a proportionately

smaller reduction in the response to NaCl than it does in

rodents, and it appears to have no effect on saltiness. Rather,

amiloride has been shown to specifically reduce the sour side

taste of NaCl, Nagluconate, and LiCl. Therefore conclusions

about the effects of amiloride on taste quality based on rodent

electrophysiology are questionable.. 2609-46-3; 7647-14-5.

164. Steinlein, O. [Familial nocturnal frontal lobe epilepsy. Clinical

aspects and genetics]. Familiare nachtliche

Frontallappenepilepsie. Klinik und Genetik. Nervenarzt. 1996

Oct; 67(10): 870-4; ISSN: 0028-2804.

GERMANY. Autosomal dominant nocturnal frontal lobe epilepsy

(ADNFLE) is a disease entity that has only recently been

discovered. Its clinical variability and the frequently missed

EEG features are probably some of the reasons why this

disease is often overlooked or misdiagnosed. In a large

Australian pedigree, a link was found between ADNFLE and

polymorphic markers on chromosome 22q13.2-q13.3. Mutation

analysis identified a mis-sense mutation in the gene coding

for the alpha 4 subunit of the neuronal nicotinic acetylcholine

receptor. The mutation was found in all affected family

members. Thus, for the first time a likely relationship

between an idiopathic epilepsy and a specific gene has been

found. Additional studies will be needed to clarify the

underlying pathologic mechanism. Furthermore, the hypothesis

that other members of this multigene family are involved in

epileptic diseases appears attractive.. 0; 0.

165. Supprian, T.; Kalus, P. [Sexual dimorphism of the human brain--a

review of the literature]. Sexueller Dimorphismus des

menschlichen Gehirns--eine Literaturubersicht. Fortschr-

Neurol-Psychiatr. 1996 Oct; 64(10): 382-9; ISSN: 0720-4299.

GERMANY. Some findings of neurobiological brain research

regarding structural sex differences of the human brain are

reviewed and discussed. Besides the well known difference in

brain size, especially some cell groups of the hypothalamus

display differences between the sexes. The results obtained

for other regions, such as the corpus callosum and other

commissural systems, are inconclusive. Further dimorphisms

involve the temporal lobes and sex-specific brain asymmetry.

These differences seem to be subtle and are superimposed by

high interindividual variability. Finally, little morphological

support is found for behavioural differences between the

sexes.

166. Tardieu, M. [The brain in children and the human immunodeficiency

virus (HIV-1) (editorial)]. Le cerveau de l'enfant et le virus de

l'immunodeficience humaine (VIH-1). Arch-Pediatr. 1996 Jun;

3(6): 523-7; ISSN: 0929-693X.

FRANCE.

167. Tashiro, K.; Goto, I.; Kanazawa, I.; Kowa, H.; Kuno, S.; Mizuno, Y.;

Ogawa, N.; Yanagisawa, N. Eight-year follow-up study of

bromocriptine monotherapy for Parkinson's disease. Eur-

Neurol. 1996; 36 Suppl 1: 32-7; ISSN: 0014-3022.

SWITZERLAND. An 8-year nationwide study of bromocriptine

monotherapy and combination therapy with bromocriptine and

levodopa in Parkinson's disease is reported. Fifteen patients

were on bromocriptine monotherapy, and 44 patients on

bromocriptine combined with levodopa for a certain time

during an 8-year period. By judging from Hoehn and Yahr's

grading, 4 of the 15 patients in the monotherapy group were in

a better condition than before treatment, while 7 cases

remained in the same grading, and only 4 showed deterioration.

On the other hand, 26 of 44 patients on combination therapy

showed more advanced grading at the end of 8 years compared

to the stage at the onset of the trial. Maintenance doses of

bromocriptine in the two groups were 12-13 mg per day, and

levodopa doses were kept at a relatively low level (310-370

mg per day) during this study period. Whether dopamine

receptor agonists have neuroprotective effect or not is

extremely difficult to prove in human subjects, but this type

of long-term follow-up study might give some clues as to

these important questions.. 0; 0; 0; 25614-03-3.

168. Temlett, J. A. Parkinson's disease: biology and aetiology. Curr-

Opin-Neurol. 1996 Aug; 9(4): 303-7; ISSN: 1350-7540.

UNITED-STATES. The cause of dopamine cell death, thought to

be the primary neurocytologic defect in idiopathic Parkinson's

disease, remains unknown. Mitochondrial oxidative dysfunction

causes premature cell death, and may be linked to accelerated

apoptosis, excessive free and toxic radicals, deficient

neurotrophic factors or combinations of these detrimental

factors. Neurochemical imbalances result both in the

substantia nigra and neostriatum, resulting in compensatory

mechanisms that make this chronic neurodegenerative disease

difficult to evaluate. Acute parkinsonism models have

limitations when compared with chronic disease states, and

caution should be present when comparing 'parkinsonism' data

with human disease. Better understanding of classical

neurotransmitters, neuroactive peptides and neurotrophic

factors, will hopefully lead to more rational treatment

approaches, cellular support strategies, and an understanding

of the causes of this disease. Glial derived neurotrophic factor

looks the most promising neurotrophic candidate so far tested

in culture and in vivo. The result of clinical trials utilizing

neurotrophic factors, both as mesencephalic implant support

strategies and as definitive treatment of idiopathic

Parkinson's disease, are awaited with cautious optimism.. 51-

61-6.

169. Thomas, P. K.; Hoffbrand, A. V. Hereditary transcobalamin II

deficiency: a 22 year follow up [letter]. J-Neurol-Neurosurg-

Psychiatry. 1997 Feb; 62(2): 197; ISSN: 0022-3050.

ENGLAND. 0; 68-19-9.

170. Ullman, J. S.; Bederson, J. B. Hypertensive, hypervolemic,

hemodilutional therapy for aneurysmal subarachnoid

hemorrhage. Is it efficacious? Yes. Crit-Care-Clin. 1996 Jul;

12(3): 697-707; ISSN: 0749-0704.

UNITED-STATES. Vasospasm is an important contributor to

death and disability after aneurysmal SAH. CBF is decreased

after SAH and correlates inversely with the severity of the

clinical grade. It is necessary to avoid hypotension and

hypovolemia, which can exacerbate an already reduced CBF,

resulting in critically low perfusion. There have been no

human, prospective, randomized trials of HHH therapy. This is

attributable, perhaps, to the fact that such trials are difficult

to blind. Nevertheless, there is strong evidence that HHH

therapy can reverse the delayed onset of profound neurologic

deficits by restoring blood flow to ischemic regions, and its

prophylactic use can reduce the incidence and severity of DID.

171. Vallarino, M.; Goula, D.; Trabucchi, M.; Masini, M. A.; Chartrel, N.;

Vaudry, H. Immunocytochemical localization of atrial

natriuretic factor and autoradiographic distribution of atrial

natriuretic factor binding sites in the brain of the African

lungfish, Protopterus annectens. J-Comp-Neurol. 1996 Nov 18;

375(3): 345-62; ISSN: 0021-9967.

UNITED-STATES. The localization of atrial natriuretic factor

(ANF)-immunoreactive elements was investigated in the brain

of the African lungfish, Protopterus annectens, by using

antisera raised against rat and human ANF(1-28).

Concurrently, the distribution of ANF binding sites was

studied by autoradiography using radioiodinated human ANF(1-

28) as a tracer. In general, there was a good correlation

between the distribution of ANF-immunoreactive structures

and the location of ANF binding sites in several areas of the

brain, particularly in the ventral part of the medial

subpallium, the rostral preoptic region, the preoptic

periventricular nucleus, the caudal hypothalamus, the neural

lobe of the pituitary, and the mesencephalic tectum. In

contrast, mismatching was observed in the pallium (which

contained a high density of binding sites and a low

concentration of ANF immunoreactive elements) as well as in

the lateral subpallium and the medial region of the ventral

thalamus, in which a low concentration of binding sites but a

high density of ANF-immunoreactive fibers were detected. The

present data provide the first localization of ANF-related

peptides in the brain of dipnoans and the first anatomical

distribution of ANF binding sites in the brain of fish. The

results show that the ANF peptidergic systems of P. annectens

exhibit similarities with those previously described in the

frog Rana ridibunda, supporting the existence of relationships

between dipnoans and amphibians. The location of ANF-like

immunoreactivity and the distribution of ANF binding sites

suggest that ANF-related peptides may act as hypothalamic

neurohormones as well as neurotransmitters and/or

neuromodulators in the lungfish brain.. 0; 0; 85637-73-6.

172. van Dijk, M. A.; Chang, P. C.; Peters, D. J.; Breuning, M. H.

Intracranial aneurysms in polycystic kidney disease linked to

chromosome 4. J-Am-Soc-Nephrol. 1995 Dec; 6(6): 1670-3;

ISSN: 1046-6673.

UNITED-STATES. Autosomal dominant polycystic kidney

disease is genetically heterogenous, with at least two

chromosomal loci accounting for the disease. When the

mutation is located on chromosome 16 (PKD1), extra-renal

manifestations such as the rupture of intracranial aneurysms

are well known. In the case of localization on chromosome 4

(PKD2), in which the renal disease runs a milder course, not

much is known about the incidence of extrarenal

manifestations. A PKD2 family is reported in which two

members had subarachnoidal bleeding due to intracranial

aneurysms; there was strong clinical evidence of

subarachnoidal bleeding in a third family member. This

indicates that the familial clustering of intracranial

aneurysms may also occur in PKD2 families. Because of the

considerable mortality and morbidity of intracranial

aneurysms, screening with magnetic resonance angiography in

PKD2 patients with a positive family history of intracranial

aneurysms is recommended.

173. Voorn, P.; Brady, L. S.; Berendse, H. W.; Richfield, E. K.

Densitometrical analysis of opioid receptor ligand binding in

the human striatum--I. Distribution of mu opioid receptor

defines shell and core of the ventral striatum. Neuroscience.

1996 Dec; 75(3): 777-92; ISSN: 0306-4522.

UNITED-STATES. Changes in opioid neurotransmission have

been implicated in several basal ganglia-related neurological

and psychiatric disorders. To gain a better insight into the

opioid receptor distribution in the normal human striatum, we

examined in post mortem brain the distribution of the mu

opioid receptor using ligand binding of [3H]O-ala2-N-methyl-

phe4, gly-ol5-enkephalin. Our results indicate at the regional

level the presence of a dorsal-to-ventral high-to-low density

gradient in the striatum, with lowest densities in the ventral

one-third of the putamen and in the nucleus accumbens. At the

subregional level, the nucleus accumbens shows two major

types of heterogeneities. First, low vs intermediate binding

densities distinguish the core and shell subdivisions,

respectively. The low-density core and intermediate-density

shell regions extend into the putamen and are therefore

characteristic for the entire ventral striatum. The second type

of heterogeneity is formed by small areas located along the

ventral contours of the nucleus accumbens and putamen that

display the highest binding density of the entire striatum.

Since these areas can also be recognized in the distribution

patterns of other markers and in the cytoarchitecture, they

appear to possess a separate identity. To emphasize their

special neurochemical characteristics we propose the

description "neurochemically unique domains in the accumbens

and putamen". The present results, with the difference

between core and shell of the ventral striatum as the most

prominent outcome, together with the notion that the

connectional relationships and neurochemical organization of

the striatum are very heterogeneous, suggest a strong regional

functional differentiation for mu receptor function in the

human striatum.. 0; 0; 0; 78123-71-4.

174. Walot, I.; Miller, B. L.; Chang, L.; Mehringer, C. M. Neuroimaging

findings in patients with AIDS. Clin-Infect-Dis. 1996 Jun;

22(6): 906-19; ISSN: 1058-4838.

UNITED-STATES. An increasing number of patients are

presenting with central nervous system complications of

human immunodeficiency virus infection. New imaging

technologies such as magnetic resonance imaging, magnetic

resonance proton spectroscopy, single-photon emission

computed tomography, and positron emission tomography are

playing an ever-increasing role in the diagnosis of these

complications. As therapeutic modes improve, imaging may

assume a growing role in monitoring the responses to therapy

among these patients.

175. Waritz, R. S.; Steinberg, M.; Kinoshita, F. K.; Kelly, C. M.; Richter,

W. R. Thyroid function and thyroid tumors in toxaphene-treated

rats. Regul-Toxicol-Pharmacol. 1996 Oct; 24(2 Pt 1): 184-92;

ISSN: 0273-2300.

UNITED-STATES. Historically, a direct and irreversible

genotoxic reaction of a xenobiotic with DNA has been

considered to be a universal and obligatory initiating event in

the etiology of neoplasia, and it was assumed therefore that

(1) there was no threshold other than zero exposure for cancer

initiation, and (2) like radiation, exposure was additive over a

lifetime. Human exposure to xenobiotics causing neoplasia in

laboratory rodents has been regulated in many countries on

that basis. In the last decade evidence has accumulated

indicating that some neoplasia in laboratory rodents may not

be caused by a direct and irreversible interaction of

xenobiotics with DNA. In addition, it has been found that some

neoplasia caused in laboratory rodents by xenobiotics may not

be relevant for biochemical/physiological reasons. This has

raised the question whether human exposure to these

xenobiotics should be regulated by the no-threshold philosophy

used for direct-acting genotoxic xenobiotics or whether they

can be regulated by the threshold philosophy used for classical

xenobiotic-induced toxic effects. In a bioassay carried out by

the National Cancer Institute and published in 1979, toxaphene

was found to cause an increase in the occurrence of two

spontaneously occurring tumors in laboratory rodents that

since have been found to have both genotoxic and nongenotoxic

etiologies in laboratory rodents. Experiments described in this

paper are part of a program to help elucidate whether the

increased incidence of these two neoplasms in laboratory

rodents could have had a nongenotoxic origin, and thus whether

toxaphene could be regulated by a threshold approach. Forty

male rats were orally intubated with 100 mg/kg/day technical

grade toxaphene in corn oil for 3 days. The dose was reduced to

75 mg/ kg/day on Day 4 due to toxicity. This lower dose was

administered daily for 25 days. Another group of 40 male rats

was orally gavaged daily with equivalent volumes of corn oil.

After 0, 7, 14, and 28 doses, 10 test and 10 vehicle control

animals were sacrificed for gross and histopathological

examination of thyroid, parathyroid, and pituitary glands.

Weights of these endocrine organs, body weights, and brain

weights were determined. Prior to sacrifice, a blood sample

was obtained from each animal for preparation of serum for

analyses of thyroid stimulating hormone (TSH), thyroxine (T4),

thyroid hormone (T3), and reverse T3 (rT3). Thyroid glands

were evaluated microscopically for follicular cell

hypertrophy, hyperplasia, and colloid storage. There were

significant time-related increases in serum TSH in the test

animals after 7, 14, and 28 doses of toxaphene. The serum

levels of T3, T4, rT3, and corrected T3 (CrT3) in the test group

were not significantly different from controls at each

interval. Thyroid gland weights and thyroid to brain weight

ratios were not significantly (p > 0.05) increased in the test

group at each sacrifice interval. Pituitary weight, brain

weight, and the ratios of these organ weights to body weights

were similar in the test and control groups at each sacrifice

interval. Thyroid follicular cell hypertrophy and intrafollicular

hyperplasia increased and thyroid follicular cell colloid stores

decreased with duration of treatment with toxaphene. The

hormonal and histopathologic changes seen in the test group

were consistent with increased excretion of T3 and/or T4

resulting from cytochrome P450 enzyme induction in the liver.

This mechanism for thyroid neoplasia is not known to occur in

humans.. 0; 0; 0; 8001-35-2; 9002-71-5.

176. Watson, J. D. Functional imaging studies of human visual cortex.

Clin-Exp-Pharmacol-Physiol. 1996 Oct; 23(10-11): 926-30;

ISSN: 0305-1870.

AUSTRALIA. 1. The past decade has seen a burgeoning of

functional imaging studies of cerebral activity in normal

humans. Much of this week has been performed on the visual

system, which is an important and often conveniently studied

part of the brain. 2. Previously, what we believed about the

functional anatomy of the human visual system was almost

entirely obtained by studying individual patients with cerebral

lesions and from experiments in animals. Early functional

imaging experiments were often quite simple, descriptive

exercises. 3. Techniques such as positron emission tomography

have become quite mature; with this and increasing experience

on the part of the investigators, the experiments performed

have become more novel. Functional imaging methods have

become part of the mainstream of investigations to be used

for research on vision. They already have led to novel

hypothesis about how aspects of this system work.

177. Weisgraber, K. H.; Mahley, R. W. Human apolipoprotein E: the

Alzheimer's disease connection. FASEB-J. 1996 Nov; 10(13):

1485-94; ISSN: 0892-6638.

UNITED-STATES. Human apolipoprotein (apo) E, long known for

its prominent role in cholesterol transport and plasma

lipoprotein metabolism, has recently emerged as a major

genetic risk factor for Alzheimer's disease, a

neurodegenerative disorder. In a variety of populations

worldwide, one of the three common alleles of apoE, apoE4, is

overrepresented in Alzheimer's subjects compared with age-

and sex-matched controls. The genetic and epidemiologic

evidence suggests that apoE is a major susceptibility gene for

Alzheimer's disease; it likely accounts for a major portion of

the genetic heterogeneity in the disease. Although its role in

the development of Alzheimer's disease is unknown,

biochemical and cell biology studies are providing important

insights into how apoE may be involved in neurodegenerative

disorders. Based on an understanding of the structure and

function of apoE in lipid transport and cellular metabolism, it

is suggested that apoE is involved in a final common pathway

of neuronal repair and remodeling: apoE3 (most common allele)

supporting effective repair and remodeling after neuronal

injury by noxious agents, and apoE4 being less effective in

these processes.. 0; 0; 0; 0; 0; 9005-49-6.

178. Werring, D. J.; Chaudhuri, K. R. Human immunodeficiency virus-

related progressive multifocal leukoencephalopathy presenting

with an akinetic rigid syndrome. Mov-Disord. 1996 Nov; 11(6):

758-61; ISSN: 0885-3185.

UNITED-STATES.

179. Wilkinson, I. D.; Paley, M. N.; Hall Craggs, M. A.; Chinn, R. J.; Chong,

W. K.; Sweeney, B. J.; Kendall, B. E.; Miller, R. F.; Newman, S. P.;

Harrison, M. J. Cerebral magnetic resonance relaxometry in HIV

infection. Magn-Reson-Imaging. 1996; 14(4): 365-72; ISSN:

0730-725X.

UNITED-STATES. A prospective, cross-sectional study was

designed to determine the magnetic resonance relaxation

times of cerebral white matter in human immunodeficiency

virus (HIV) infected individuals. T1 and T2 were estimated at

1.5 T using four-point methods. Seventy-five HIV-1

seropositive subjects, 48 seronegative blood donors, and 17

seronegative homosexual men were studied. Associations

between relaxometry and clinical classification, neurological

status, immunological status, and qualitative MRI were

investigated. Statistically significant differences in white

matter T1 relaxation time were found comparing low-risk

control and AIDS groups (p < .005), seropositive subjects with

neurological signs and those without (p < .005), and subjects

with low (CD4 < or = 200 x 10(6)/l) and high (CD4 > 200 x

10(6)/1) CD4 cell counts (p < .05). These findings add to the

body of information that reveals no HIV-related change in the

brain before the onset of symptomatic immunosuppression and

go someway to validating the previous visually rated,

qualitative findings. Statistically significant difference in

white matter T2 relaxation time were also found comparing

the two control groups (p < .005) highlighting the need for

appropriate controls.

180. Wilson, D. J.; Kim, D. S.; Clarke, G. A.; Marshall Clarke, S.; Moss, D.

J. A family of glycoproteins (GP55), which inhibit neurite

outgrowth, are members of the Ig superfamily and are related

to OBCAM, neurotrimin, LAMP and CEPU-1. J-Cell-Sci. 1996

Dec; 109( Pt 13): 3129-38; ISSN: 0021-9533.

ENGLAND. We have previously identified a

glycosylphosphatidylinositol-linked glycoprotein of 55 kDa

(GP55) which inhibits neurite outgrowth. We now provide

evidence that GP55, isolated from adult chick brain, consists

of at least two bands, both of which are active, i.e., block

outgrowth of neurites from chick dorsal root ganglion neurons.

An antiserum raised against the adult proteins reverses the

inhibition and preliminary experiments suggest that GP55 is

restricted to the nervous system, increases during

development from very low levels at embryonic day 10 and is

most abundant after hatching. Immunofluorescence reveals

that GP55 is expressed on neurons cultured from an embryonic

day 14 chick brain but is barely detectable on embryonic day

10 dorsal root ganglion neurons or embryonic day 8 forebrain

neurons; the neurons which respond to substrate-bound GP55.

Peptide sequencing revealed considerable homology with

OBCAM, a protein previously identified on the basis of binding

opiates. Nested polymerase chain reaction using primers to the

OBCAM sequence and internal primers to GP55 peptides

produced two different polymerase chain reaction fragments

with homology to OBCAM. A full length clone (E19S)

corresponding to one polymerase chain reaction product and a

partial length clone (E14S) corresponding to the second have

been isolated from an embryonic chick brain library. Both are

members of the immunoglobulin superfamily and have (or are

expected to have) three C2 domains. E19S has 90% homology

with LAMP at the amino acid level. This sequence only

partially matches the peptides from the adult protein and

hence is probably not a major component of the adult proteins.

E14S (GP55-A) has 83% homology to OBCAM at the amino acid

level over the region sequenced. The sequence matches several

of the peptides from the adult protein and is hence likely to

correspond to a major component of the adult proteins. Thus

members of the GP55 family are related to OBCAM,

neurotrimin, LAMP and a recently discovered chick protein

CEPU-1. Our results suggest molecules within this family are

capable of acting as cell adhesion molecules and inhibitors of

neurite outgrowth.. 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0.

181. Yamada, T. [The objective and perspective of recording electrical

activity from the central nervous system]. Rinsho-Shinkeigaku.

1995 Dec; 35(12): 1323-31; ISSN: 0009-918X.

JAPAN. In 1929 Hans Bergr successfully recorded electrical

activity from the human brain using surface scalp electrodes.

Since, the EEG has brought significant contributions to the

fields of clinical neurology and neurophysiology. As a clinical

diagnostic tool, the EEG has provided information for

functional as well anatomical (structural) brain disturbances.

As a functional diagnosis, the EEG is far superior to other

functional tests such as PET, SPECT or functional MRI because

of its excellent temporal resolution representing moment to

moment changes in the level of consciousness. However, the

progress has been hampered due to difficulty in quantifying

EEG data because of its extreme dynamics and variability,

which perhaps reflects yet unknown brain functions. This

difficulty will be overcome by improved quantification

methods and statistical measures using various computer

applications including topographic mapping, power spectrum

analysis, covariance, correlation or coherence function.

Because of its poor spacial resolution, the EEG has

relinquished its place to CT and MRI scans as an anatomical

diagnostic tool. The surface recorded electrical activity is

greatly attenuated and distorted by the time it reaches to the

scalp. This is due to the inhomogeneous tissues (CSF, dura,

skull, scalp) that intervene between the recording electrodes

and cortical surface. Because the human body or head consists

of electroconductive media of various geometries, current

distortion, far-field potentials or paradoxical lateralizations

further complicate the interpretation of EEG in postulating the

location of anatomical generator sources from surface

recorded EEG. Advanced computer technology is in progress to

quantify the EEG data by taking into account the factors of

conductivity, geometry shape and individual head size. This

will improve the accuracy of localizing current generator

sources in relationship to brain anatomy. By solving these

problems in a methodical fashion, EEG will become the

revelation for understanding the functional anatomy of brain

and will step closer to Berger's dream, "EEG is a window of

human mental activity".

182. Yew, D. T.; Webb, S. E.; Wong, C. K.; Hui, K. S. Differential

expression of the soluble 170 kDa brain protein in the fetal

and adult human brain. Int-J-Dev-Neurosci. 1996 Aug; 14(5):

551-7; ISSN: 0736-5748.

ENGLAND. The expression of the soluble 170 kDa brain protein

(BP170) was studied in the developing human brain. Using

immunohistochemical methods, it was possible to demonstrate

that BP170 was expressed very strongly in the visual cortex

up to approximately 27 weeks of gestation. After this time,

the level of expression was reduced so that by adulthood the

levels of BP170 were negligible. Similarly, BP170 was

expressed in the hippocampus at all stages of development;

however, unlike in the visual cortex, this protein was still

apparent, albeit at low levels, in the adult. In addition, BP170

was co-expressed with tyrosine hydroxylase which suggests

its possible role in the dopamine pathway.. EC 1.14.16.2; EC

2.3.1.6; 0.

183. Zaidel, D. W. The case for a relationship between human memory,

hippocampus and corpus callosum. Biol-Res. 1995; 28(1): 51-7;

ISSN: 0716-9760.

CHILE. Unilateral brain damage which includes the

hippocampus leads to memory impairments consistent with

hemispheric specialization on the same side. Damage to the

corpus callosum, the major connecting pathway between the

left and right hemispheres, also leads to memory impairments.

This suggests both hemispheric specialization on the

hippocampal level and a critical role for the corpus callosum

in memory functions. A complete hippocampal formation is

present on either side of the brain but traditionally only one is

studied. However, a comparison between the neuronal

populations in the hippocampus on both sides revealed

asymmetry in connectivity among hippocampal subfields. The

profile of memory impairments of commissurotomy ('split-

brain') patients is described. The results are discussed in

terms of a relationship between hippocampus and corpus

callosum in humans. As hemispheric specialization evolved,

inter-hippocampal connections became less important and the

corpus callosum became prominent in memory functions.

184. Zihl, J. [The contribution of neuropsychology to psychiatry]. Der

Beitrag der Neuropsychologie zur Psychiatrie. Fortschr-

Neurol-Psychiatr. 1996 Oct; 64(10): 403-17; ISSN: 0720-4299.

GERMANY. Human neuropsychology is the study of brain-

behavior relationships based on the analysis of functional

disturbances after brain damage. The assessment and analysis

of pathological states and processes in the brain on cognition,

speech and language, praxis, motivation and affectivity,

represent the main topics of neuropsychological research.

Patients with psychiatric disorders very often exhibit

cognitive impairments which should also be assessed by means

of specific neuropsychological diagnostic tools. The advantage

of such tools is their validity and reliability which allow

accurate qualitative and quantitative analysis and

characterization of the various cognitive impairments.

Neuropsychological methods of assessment can also be used

for follow-up measurements, for example, in studies on the

effect of medication. Finally, the outcome of a comprehensive

neuropsychological assessment can provide a useful basis for

the treatment of cognitive impairments in psychiatric

patients using means that have proved successful in brain-

damaged patients.

185. Zoccoli, G.; Lucchi, M. L.; Andreoli, E.; Bach, V.; Cianci, T.; Lenzi, P.;

Franzini, C. Brain capillary perfusion during sleep. J-Cereb-

Blood-Flow-Metab. 1996 Nov; 16(6): 1312-8; ISSN: 0271-678X.

UNITED-STATES. Brain capillary perfusion was evaluated in

the different states of the wake-sleep cycle-quiet

wakefulness (QW), quiet sleep (QS), and active sleep (AS)-in

rats. The extent of the perfused capillary network was

determined by intravascular distribution of a fluorescent

marker. Evans blue (EB); it remained unchanged across the

three behavioral conditions, QW, QS, and AS. The anatomical

network was assessed by alkaline phosphatase (AP)

endothelial staining, which is known to underestimate the

number of existing capillaries. The resulting number of AP

profiles were, therefore, significantly lower than the number

of EB profiles, but the percentage of AP-stained capillaries

that were perfused (96%) was also unchanged across the

behavioral conditions. The results indicate that no capillary

recruitment accompanies the wake-sleep cycle. Capillary

surface area is a relevant factor in determining exchanges

across the blood-brain barrier. In the absence of capillary

recruitment (relative constancy of the surface area), the CBF

changes during sleep should preferentially affect flow-limited

with respect to diffusion-limited transport.. 0; 314-13-6.

186. Zohar, A. H.; Pauls, D. L.; Ratzoni, G.; Apter, A.; Dycian, A.; Binder,

M.; King, R.; Leckman, J. F.; Kron, S.; Cohen, D. J. Obsessive-

compulsive disorder with and without tics in an

epidemiological sample of adolescents. Am-J-Psychiatry.

1997 Feb; 154(2): 274-6; ISSN: 0002-953X.

UNITED-STATES. OBJECTIVE: This study was undertaken to

discriminate subtypes of obsessive-compulsive disorder in

adolescents. METHOD: Forty individuals with obsessive-

compulsive spectrum disorders were ascertained from an

epidemiological sample of 861 adolescents. Interviews were

conducted by child psychiatrists using semistructured

diagnostic interviews, including a clinician-rated Yale-Brown

Obsessive Compulsive Scale. Discriminant analysis was

performed to compare the scores on the Yale-Brown scale of

groups with and without comorbid tics and to compare boys

and girls. RESULTS: Adolescents with tics were more prone to

aggressive and sexual images and obsessions than were

adolescents without tics; these differences could not be

wholly attributed to sex differences. CONCLUSIONS: The

subtypes among unreferred adolescents are similar to those of

adult patients with obsessive-compulsive disorder with and

without Gilles de la Tourette syndrome. Subtypes evident in

adulthood may be established relatively early in the natural

course of obsessive-compulsive disorder.