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V Sazdovitch

Publications and source records attributed to V Sazdovitch.

34 records · Page 2Linked to original sources

[Fronto-temporal degenerative dementia. A modern neuropathologic approach].

The classification of degenerative dementias with fronto-temporal atrophy has been debated since the description of Pick's disease. The study of a clinico-pathological series of 10 cases using immunohistochemistry lead to the following conclusions: reserving the name of Pick's disease to those cases with argyrophilic inclusions, the most recognisable and characteristic marker at neuropathological examination, allows an easy and reliable diagnosis; keeping on with the splitting of these disorders into various clinico-pathologic entities seems today more useful than grouping them into a single syndrome until new data, based for example on genetic analysis, show that different phenotypes correspond to the same disease.

Adult↗

DNA breaks detected by in situ end-labelling in dorsal root ganglia of patients with AIDS.

Distal sensory axonal polyneuropathy (DSP) is the most frequent HIV-associated peripheral neuropathy. DSPs tend to occur in full-blown AIDS and worsen as CD4 cell counts decrease in blood. To assess a possible role for apoptosis in the pathogenesis of the neuropathy, we used in situ end-labelling (ISEL) detecting DNA strand breaks in DRG neurons of 19 HIV-infected patients, of whom nine had axonal polyneuropathy, and 11 controls. Sensory neurons with ISEL-assessed DNA breaks were observed in 9/19 patients with AIDS, 0/3 patients with pre-AIDS, and 1/11 controls. The prevalence of DNA breaks in neurons was higher in AIDS patients than in controls (P < 0.05). Among AIDS patients, DNA breaks in neurons were more abundant in patients with peripheral neuropathy (P < 0.04). It is possible that DNA breaks of DRG neurons induce the axonopathy and consequently play a role in the pathogenesis of DSP. It cannot be excluded, however, that DNA breaks could represent the result rather than the cause of axonopathy. We suggest that ISEL may detect neurons that were primed to apoptosis before death in relation with the HIV infection, and undergo DNA fragmentation at time of death, rather than neurons that underwent premortem both priming and triggering steps of the apoptotic process. This hypothesis could explain why most ISEL-positive neurons lack typical apoptotic morphology and why normal controls do not show ISEL positive cells.

Acquired Immunodeficiency Syndrome↗

Identification of crystals in kidneys of AIDS patients treated with foscarnet.

Three acquired immune deficiency syndrome patients given foscarnet to treat cytomegalovirus retinitis developed renal failure with crystal deposits within the renal glomeruli. We identified these crystals as a mixture of sodium salt, calcium salt, and a mixed salt containing both sodium and calcium ions. This composition has not been previously reported. Foscarnet can complex available ionized calcium and secondarily precipitate in glomeruli. The percentage of complexing depends on calcium concentration in serum and the poor calcium salt solubility.

AIDS-Related Opportunistic Infections↗

[Diseases transmitted by non-conventional agents ("prions"): nosology and diagnosis].

Transmissible non conventional agents are currently called "Prions". This is not a neutral terminology: the attractive Prion hypothesis (the infectious agent being a protein able to replicate in the absence of DNA or RNA) due to Stanley Prusiner is the prevalent one, and has shown to be heuristic, but has not been formally proven and does not easily explain all the data, unless modified and expanded. No simple account has been given for the very unusual physical, chemical, and biological properties of non conventional agents. These infectious agents are associated with degenerative diseases of the nervous system that are either the consequence of a genetic mutation or develop spontaneously in apparently normal individuals, and then can be transmitted to various susceptible hosts, including man. Thus, non conventional agents cannot be considered only as fascinating biological enigmas. They constitute a challenge for public health. The changing characteristics of prion-associated diseases has led to a renewing of their clinical and neuropathological diagnostic criteria. A brief survey of the nosology and neuropathology of prions diseases, with emphasis on new data and on difficulties, is provided. A simple classification based on the familial, sporadic or infectious variety of the disease is suggested. Familial diseases can be named according to the genetic disorder. Sporadic and infectious diseases can be classified following the main clinical symptoms and signs, and the presence or absence of amyloid plaques in the brain, until new tools (analysis of the glycosylation pattern of PrP, strain recognition) allow a more precise nomenclature. The new epidemiology of Prion disorders allowed by these new approaches relies on a full study of Prion diseases affected patients, which necessarily involves their genetic study, and the analysis of brain tissue. This, for practical and ethical reasons, is better achieved by autopsy.

Diagnosis, Differential↗

Human immunodeficiency virus type 1 DNA and RNA load in brains of demented and nondemented patients with acquired immunodeficiency syndrome.

The relationship between dementia and human immunodeficiency virus type 1 (HIV-1) cerebral load is not clearly understood. We used immunohistochemistry and competitive polymerase chain reaction to evaluate the density ofgp 41 immunostained cells and the amount of HIV-1 DNA and RNA in the midfrontal gyrus of 21 HIV-1 infected patients, nine of whom were demented. The amounts of HIV-1 DNA and RNA, and the density of gp 41-positive cells were significantly linked. In this small series of cases, (1) although as a mean, there was a larger viral load in demented patients than in nondemented, this did not reach the significance level (2) discrepancies appeared in the population under study, some demented patients having low viral loads.

AIDS Dementia Complex↗

Astrocytic adhesion molecules are increased in HIV-1-associated cognitive/motor complex.

Half of AIDS dementia cases are associated with HIV-encephalitis or myelin pallor. Another half die with no HIV-related neuropathological changes. Previous observations suggest that cerebral dysfunction may result from more subtle cellular interactions. and that some of them may be mediated by cell adhesion molecules. In the present study the expression by astrocytes and endothelial cells of intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) was analysed as a function of the neuropathological diagnosis, the density of astrogliosis and of HIV-1 positive cells, and of the mental status. Twelve AIDS cases, without focal brain lesion, eight of whom were demented, were selected from a prospective study. They were compared with six control cases with multiple sclerosis, and with six control patients without neurological disease. ICAM-1 and VCAM-1 expression was localized by immunofluorescence and confocal microscopy. HIV protein gp41 was detected by immunohistochemistry on adjacent sections. Endothelial expression of ICAM-1 and VCAM-1 was significantly up-regulated in all AIDS patients. VCAM-1 only was related to myelin pallor. The density of VCAM-1 or ICAM-1 positive astrocytes increased in demented AIDS patients, independently of the neuropathological findings or the density of gp41 positive cells. Expression of cell adhesion molecules, together with other secondary mechanisms such as secretion of cytokines may play a role in the pathogenesis of white matter lesions leading to HIV-1-associated cognitive changes.

AIDS Dementia Complex↗

The neuropathologic diagnostic criteria of frontal lobe dementia revisited. A study of ten consecutive cases.

Ten successive cases from the Neuropathology Laboratory of La Salpêtrière Hospital in Paris, were selected on the presence of: dementia and prominent symptoms and signs of the frontal type; a degenerative disease without markers other than Pick cells, Pick bodies or ubiquitin-labelled non argyrophilic inclusions. We propose the following steps to diagnose the degenerative dementia associated with symptoms and signs of the frontal type: 1. If there is severe frontotemporal atrophy, severe neuronal loss and astrogliosis, many ballooned neurons and characteristic inclusions that are both tau and ubiquitin positive, the diagnosis is Pick disease. 2. If signs of motor involvement (sometimes unnoticed by the clinician) are present with mild cortical atrophy and mild spongiosis of layers II-III, the diagnosis of frontal lobe degeneration associated with motor neuron disease is warranted. Ubiquitin positive inclusions are useful, but non specific, markers. 3. When there are neither Pick inclusions nor motor neuron disease, the diagnosis may be frontal lobe atrophy lacking distinctive histology.

Adult↗

Occupational environment as risk factor for unemployment in multiple sclerosis.

INTRODUCTION: Few studies have examined the factors of occupational environment related to unemployment in multiple sclerosis (MS). MATERIAL AND METHODS: A case control-study was carried out. Cases were patients unemployed for less than five years before the study (n = 77); controls were patients currently employed (n = 94). The odds ratios of the relationship under study adjusted for sex, age, disease form and educational level, were estimated. RESULTS: Employment in the public sector, sedentary jobs and possibility of obtaining specific improvements in the work environment were found to be protective factors, while jobs needing force, rigid work schedule, manual precision, frequent moves and a daily work duration over 8 h were found as risk factors. Multivariate analyses showed that the only remaining factors were public sector jobs as protective factor (OR = 0.4), and strenuous work as risk factor (OR = 4.5). Factors were slightly different in male and female patients. CONCLUSION: This study suggests that simple and early changes in the occupational environment could maintain MS patients at work.

Adult↗

HIV-associated IgA nephropathy--a post-mortem study.

Between November 1983 and December 1991, we undertook a systematic study of kidney in deceased AIDS patients using light and immunofluorescence microscopy. Among the 116 examined kidneys (from 106 men and 10 women), nine (7.75%) showed diffuse mesangial IgA deposits. By light microscopy, glomerular lesions were absent or moderate (mesangial hypertrophy or some mesangial deposits). Urinary abnormalities were mild in all cases. Our study shows that the association between IgA nephropathy and HIV infection is not rare, and a review of the literature disclosed 18 reported cases. Some reported immunopathogenic data support the possibility of a link between HIV infection and IgA nephropathy.

Acquired Immunodeficiency Syndrome↗

Virological diagnosis of progressive multifocal leukoencephalopathy: detection of JC virus DNA in cerebrospinal fluid and brain tissue of AIDS patients.

Cerebrospinal fluid (CSF) from 12 AIDS patients with clinical signs consistent with progressive multifocal leukoencephalopathy (PML) was examined by the polymerase chain reaction (PCR) for the presence of JC virus (JCV). A specific JCV target sequence was amplified in the CSF from 9 of the 12 patients and also in brain tissue from all nine JCV-positive patients. The clinical course, neuroimaging features, and, in four cases, histopathology of brain tissue proved that the nine patients had PML. In the other three patients with central nervous system disorders, the JCV genome was undetectable by PCR and Southern blot analysis in CSF and brain tissue. The clinical course and neuroimaging features ruled out PML in these three patients. Five CSF samples and five brain tissue specimens from 10 PML-free AIDS patients with central nervous system disorders were all negative for the JCV genome by PCR and Southern blot analysis. These results show that detection of JCV in CSF by PCR is a good alternative to brain tissue studies for the virological diagnosis of PML in AIDS patients.

AIDS-Related Opportunistic Infections↗

A brain bank in a neuropathology laboratory (with some emphasis on diagnostic criteria).

The Brain Bank of La Salpêtrière Hospital (Paris) is implanted in a neuropathology laboratory. It is multipurpose, prospective, and "free of charge" for the users. Protocols are prospectively established, in collaboration with the neuroscientists. One of our major difficulties in the collection of cases concerns presently the controls: the neurological status of patients coming from Neurology departments has usually been correctly assessed but those patients are bad controls. The normality of the neurological status of patients dying in other departments is difficult to assess retrospectively. A general autopsy is performed in each case. Several systematic sampling and fixation procedures are currently in use; their pros and cons are discussed. The main safety problem we are confronted with is the risk of HIV and Jakob-Creutzfeldt transmission. We try to standardize our diagnostic procedures; criteria used in Alzheimer's disease, Parkinson's disease, Huntington's chorea are briefly reviewed. We plan, in the future, to standardize our procedures for control cases. The Brain Bank has had a very positive impact on the way this neuropathology laboratory works: it introduced new techniques; on the other hand, the adequate processing and diagnosis of the samples was, in many aspects, simplified by the collaboration with the neuropathology department. The demand for human brain samples is steadily increasing in Neuroscience, for at least 2 reasons: 1. some diseases are specifically human and lack adequate animal models (Alzheimer's disease, multisystem atrophy), or animal models may appear irrelevant in some aspects (multiple sclerosis) or finally, results obtained in animal models may have to be confronted with human pathology (AIDS ...) 2. many aspects of human neuroanatomy can not be extrapolated from animal data There are many ways of organizing a brain bank and no golden standard (Swaab et al., 1989): the neuroscientist himself may collect the samples in a given pathology or the neuropathologists may modify their practice to provide adequate samples to the neuroscientists. When the neuroscientist himself collects his own samples, he obviously proceeds more rapidly. However, he is confronted with the difficult problem of the controls, which require both a clinical follow-up and a pathological check up of the tissues, both of which may be difficult to obtain in a research unit. In our opinion, the neuropathologists are the natural "brain bankers": they are indeed naturally "rich", their job being precisely to collect human samples, in connection with the clinicians.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain↗

Effects of vigabatrin and of GABA on myelinated rat cerebellar cultures: preliminary data.

1. The aim of this study was to evaluate the effect of high concentrations of vigabatrin (gamma-vinyl GABA) and of GABA on myelin of the central nervous system cultures. 2. Explants of rat cerebellum were cultured for 14-19 days in vitro on collagen-coated coverslips in Leighton tubes. They were exposed for up to 14 days to 500 nmol ml-1 vigabatrin or to 1000 nmol ml-1 GABA. 3. Qualitative and quantitative blind examination of living cultures and of Sudan black B-stained slides showed mild toxicity of both drugs for myelinated fibres. No clear-cut differences could be demonstrated between the two compounds, although vigabatrin seemed slightly more toxic than GABA at these doses. 4. In electron microscopy, no patent intramyelinic oedema nor primary demyelination were seen. On the contrary, some degenerating myelinated fibres and astrocytic gliosis were seen in both experimental conditions. The changes involved axons as well as myelin sheaths. 5. The toxicity of GABA and vigabatrin was surprisingly mild in this very sensitive model.

Aminocaproates↗

Imaging of human brain lesions with an omega 3 site radioligand.

The topography and magnitude of increase in peripheral type benzodiazepine binding sites (omega 3 sites) was investigated autoradiographically in the brains of patients with ischemic cerebrovascular disease, with multiple sclerosis, and with malignant glioma. 3H-PK 11195, a selective omega 3 site ligand, was employed. A manyfold increase in omega 3 site density was observed in all these disease states; this increase reflects macrophage invasion or glial proliferation or both as demonstrated by neuropathological studies carried out in parallel. There was an excellent spatial correlation between increased omega 3 site densities and extent of the lesion histologically. Specifically, an elevated density of omega 3 sites was observed in the plaques of demyelination in multiple sclerosis patients, in the periphery of infarcted zones in stroke patients, and throughout tumor in patients with grade IV astrocytomas. As our approach is applicable to both tomographic (in vivo) and autoradiographic investigations, imaging of omega 3 sites may be considered for the detection and monitoring of the natural evolution of many disorders of the human central nervous system.

Adult↗

Neuropathological epidemiology of cerebral aging: a study of two genetic polymorphisms.

We studied whether ApoE and -219 GT (ApoE promoter) polymorphism modulates neurofibrillary tangle (NFT) and senile plaque (SP) development in aging among 190 non-institutionalized individuals (mean age 79.5 years). Analysis revealed that the mean Braak stage was higher in epsilon4 allele carriers. Once individuals with Braak stage V were excluded (n = 5), relationships between NFT and the two genotypes studied were weak, whereas in epsilon4 allele carriers, the risk of SP was multiplied by 4 to 7 in four areas (CA1, subiculum, isocortex and entorhinal cortex). This association was more pronounced in subjects under 80 years and was also observed when analysis was restricted to Braak stages 0, I and II. Epsilon 2 allele carriers appeared to have fewer lesions but, due to limited numbers, this trend was not significant. In two regions (CA1, subiculum), the number of SP increased significantly for individuals who were homozygous for the T allele of -219 GT. However the association was no longer significant when controlling for ApoE epsilon4. It should be noted that the brain of elderly subjects carrying one epsilon4 allele may not undergo senile changes.

Aged↗