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Biomedical subjects

F Gray

Publications and source records attributed to F Gray.

At least 109 records · Page 6Linked to original sources
PubMed1994

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism.

Fatal familial insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178-->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.

Codon↗
PubMed1994

Creutzfeldt-Jakob disease and cerebral amyloid angiopathy.

An 83-year-old female with no personal or familial neurological history developed progressive gait and speech disturbance and left motor deficit. She suffered intractable seizures and died 3 months after the onset of neurological signs. Neuropathology showed severe spongiosis and gliosis in the cortex and basal ganglia, and diffuse cerebral amyloid angiopathy. Immunostaining for prion protein (PrP) showed intense PrP positivity in areas of confluent spongiosis and some granular staining in astrocytes. The cortical vessel walls stained positively for beta/A4 amyloid but not for PrP amyloid. Both types of amyloid were only observed in pericapillary parenchyma, in areas with severe spongiosis. There were only a few tangles and neuritic plaques in the temporal cortex; amyloid plaques were not present either by silver stains or immunostains. There was neither arteriopathic leukoencephalopathy nor cerebral hemorrhage. Immunoblot analysis of brain extracts revealed an abnormal proteinase K-resistant isoform of PrP. Association of Creutzfeldt-Jakob disease and Cerebral amyloid angiopathy in the absence of Alzheimer changes in unusual. The association of PrP and beta/A4 amyloid deposits could have been fortuitous in an 83-year-old patient. An etiopathogenic relationship between beta/A4 amyloid deposition and PrP accumulation may also be considered.

Aged↗
PubMed1994

Primary Sjögren's syndrome and gamma heavy chain disease.

We describe a patient who has primary Sjögren's syndrome associated with asymptomatic gamma heavy chain disease and a tubulointerstitial nephritis. Sjögren's syndrome is known to be complicated by lymphoproliferative disorders and tubulointerstitial nephritis but gamma heavy chain disease is rare (approximately 100 cases described). There is one previously reported case of gamma heavy chain disease associated with primary Sjögren's syndrome and 2 cases associated with secondary Sjögren's syndrome. Our patient and the 3 other patients described in the literature did not have evidence of an underlying lymphoproliferative disorder.

Aged↗
PubMed1994

Varicella-zoster virus infection of the central nervous system in the acquired immune deficiency syndrome.

Productive varicella-zoster virus (VZV) infection of the central nervous system (CNS) was demonstrated in 11 acquired immune deficiency syndrome (AIDS) patients using immunocytochemistry and in situ hybridization. A characteristic zoster skin eruption was seen in only four cases. From our own series and 11 other cases in the literature, we identified five clinico-pathological patterns of VZV infection of the CNS in AIDS patients which could occur simultaneously. (i) Multifocal encephalitis predominantly involving the white matter, likely to be due to haematogenous spread of the infection was found in four cases. (ii) Ventriculitis was found in three cases. In two cases there was complete acute or chronic necrosis of the ventricular wall with marked vasculitis; in the third, the ependymal lining appeared irregular with foci of VZV-infected ependymal cells, some of which protruded into the ventricular lumen. (iii) Acute haemorrhagic meningo-myeloradiculitis with necrotizing vasculitis was observed in two cases. In one, this was associated with ventriculitis and was possibly due to shedding of infected ependymal cells into the ventricular lumen and secondary seeding of the CSF. (iv) Focal necrotizing myelitis was seen in one case. It followed cutaneous herpes zoster and was considered to result from neural spread from the diseased dorsal root ganglion similar to cases previously described of encephalitis limited to the visual system following VZV ophthalmicus, or bulbar encephalitis following a trigeminal zoster. (v) Vasculopathy involving leptomeningeal arteries and causing cerebral infarcts was seen in four cases, it was associated with meningitis in most cases. These findings are in keeping with the observation in non-AIDS patients that VZV spread to the CNS may follow different routes. Our study tends to show that VZV infection of the CNS occurs more frequently in AIDS than previously suspected and suggests that it must be considered as a diagnosis in cases of encephalitis, ventriculitis, focal myelitis, acute myeloradiculitis and cerebral infarcts in these patients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Zidovudine twice daily in asymptomatic subjects with HIV infection and a high risk of progression to AIDS: a randomized, double-blind placebo-controlled study. The European-Australian Collaborative Group (Study 017)

OBJECTIVE: To evaluate the efficacy of zidovudine given twice daily in subjects with asymptomatic HIV-1 infection and a high risk of progression to AIDS. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Multicentre study in five European countries and Australia. PATIENTS: Asymptomatic subjects (n = 329) with CD4 cell counts between 200 and 400 x 10(6)/l, or if > 400 x 10(6)/l, subjects with HIV p24 antigenaemia (> 10 pg/ml). INTERVENTION: Patients were randomly assigned to receive zidovudine 500 mg or placebo twice daily for 104 weeks, following a 250 mg four times daily dose regimen for the first 4 weeks. MAIN OUTCOME MEASURES: The primary end-point was the development of AIDS or severe AIDS-related complex (ARC). Before unblinding the study other end-points were defined: the development of Centers for Disease Control and Prevention (CDC) group IV disease (AIDS, severe ARC and other CDC stage IV disease) and the development of symptomatic HIV disease (AIDS, severe ARC, other CDC stage IV disease and minor HIV disease). Changes in CD4+ cell counts, p24 antigenaemia and toxicity were also reviewed. RESULTS: Median treatment duration was 57 weeks for the placebo and 60 weeks for the zidovudine group, respectively. Progression to AIDS or severe ARC occurred in 17 placebo and 12 zidovudine recipients (log-rank P = 0.26). However, in the first of the 2 study years the rate of progression to AIDS or severe ARC was significantly higher in the placebo than in the zidovudine group. Zidovudine delayed progression to symptomatic HIV disease (P = 0.01); a trend in a delay in progression to CDC stage IV disease was observed (P = 0.08). Zidovudine recipients maintained CD4+ cell counts at or above baseline levels for longer than placebo recipients (P = 0.04). HIV p24-antigen levels decreased in the zidovudine group and returned to pretreatment levels by week 36. Substantial toxicity was not observed. CONCLUSIONS: Zidovudine twice daily is effective in delaying progression to symptomatic HIV disease in high-risk, asymptomatic HIV-infected subjects. Modified definitions of clinical end-points may be useful for evaluating Phase III trials in comparable patient groups in the light of changes in the definition of AIDS and the increasing use of primary prophylaxis against opportunistic infections.

AIDS-Related Complex↗
PubMed1994

Zidovudine therapy and HIV encephalitis: a 10-year neuropathological survey.

OBJECTIVE: To assess the effect of zidovudine on productive HIV infection of the brain. DESIGN: To correlate the incidence of HIV-specific neuropathology with zidovudine therapy. PATIENTS: We examined 192 AIDS cases neuropathologically; 97 had never been treated with zidovudine, 72 had received zidovudine for over 3 months and until death, 23 had their treatment terminated more than 1 month before death. RESULTS: The incidence of HIV encephalitis/HIV leukoencephalopathy (HIVE/HIVL) and of multinucleated giant cells (MGC) was significantly lower in patients who had received zidovudine than in those who had never received zidovudine. The yearly incidence of HIVE/HIVL increased between 1982 and 1987 probably because of improved survival, and decreased between 1987 and 1990 although the percentage of patients treated with zidovudine increased. Since 1991 the incidence of HIVE/HIVL and of MGC increased slightly. The percentage of patients treated with zidovudine until death decreased and that of patients whose treatment was terminated increased concomitantly. In 1989 and 1990, most patients whose treatment was terminated had MGC and HIVE/HIVL. In 1991 and 1992 this incidence decreased markedly, coinciding with the introduction of dideoxyinosine therapy. CONCLUSION: Zidovudine treatment significantly reduces the occurrence of productive HIV infection of the brain in AIDS. Discontinuing zidovudine therapy may favour the occurrence of HIV encephalitis. Substitution therapy with dideoxyinosine also appears to protect against HIV-specific brain pathology.

AIDS Dementia Complex↗
PubMed1994

Immunohistochemical changes and PCR detection of HIV provirus DNA in brains of asymptomatic HIV-positive patients.

The stage of HIV infection at which the virus enters the nervous system remains poorly understood. Examination of brains of HIV-positive non-AIDS patients often shows lymphocytic meningitis, myelin pallor and gliosis, but no immunohistochemical (IHC) evidence of the virus. In this study we have examined a number of brains from HIV-positive patients with (23) and without (8) AIDS as well as brains from 5 HIV-negative controls by morphological, morphometric, IHC and polymerase chain reaction (PCR) methods in an attempt to establish at what stage of the infection HIV can be detected in the brain and to correlate its presence with the pathological changes in the cortex. HIV-1 proviral DNA was found by PCR in the cortex of the majority of AIDS and in 2 out of 8 non-AIDS cases. Astroglial reaction was observed in the cortex of the majority of AIDS brains but not in most of the non-AIDS brains which showed, in addition, a dramatic reduction of glial fibrillary acidic protein staining around blood vessels; moreover, in this group the density of microglial cells was higher than in the AIDS group. These results show that: 1) HIV proviral DNA can be found in the brains of HIV-positive non-AIDS patients; 2) in the same group there is an increase in density of microglial cells which 3) appears to be transient, since AIDS brains without neuropathology show a lower density of these cells. They also suggest that the status of 'immune reaction' existing in AIDS may predate this period.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1994

Autosomal dominant arteriopathic leuko-encephalopathy and Alzheimer's disease.

A 49-year-old man suffered from progressive dementia and seizures leading to death after 2 years. CT scans showed severe cortical-subcortical atrophy and hypodensity of the white matter. His father had died at about the same age with similar clinical signs. Two sisters and one brother were also affected. Neuropathological study revealed predominant involvement of the cerebral white matter with myelin loss, gliosis and type I lacunes. The small arteries and arterioles of the white matter and basal ganglia, and, to a lesser extent those of the subarachnoidal space, displayed fibrosis and replacement of the media by an eosinophilic, PAS positive, Congo Red negative, granular substance. Electron microscopy showed swollen myocytes surrounded by collagen, elastin and a compact electron-dense material. Immunofluorescence using antibodies against IgA, IgG, IgM, C1q and C3 stained the abnormal media weakly. In the cortex, there were diffuse senile plaques and neurofibrillary tangles. Immunohistochemistry demonstrated beta/A4 positive material in cortical senile plaques but not in arterial walls. Adventitial macrophages were, however, immunoreactive for gamma-trace. Systemic arterioles were normal. The vascular changes and leukoencephalopathy are comparable to those described in 'Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy' (CADASIL). Similar vascular changes were also observed in nonfamilial cases. An association with Alzheimer changes in the cortex has not been described previously. The relationship between both diseases and the role of each in the causation of the dementia is unclear.

Alzheimer Disease↗
PubMed1994

Selective deficit of visual size perception: two cases of hemimicropsia.

Hemimicropsia is a rare disorder of visual perception characterized by an apparent reduction of the size of objects when presented in one hemifield. We report two cases of hemimicropsia resulting from focal brain lesions. The first patient was an art teacher and could accurately depict his abnormal visual perception. He subsequently died and his brain was examined post mortem. In the second patient, micropsia was assessed by a quantified size comparison task. The size of a given object is normally perceived as constant across any spatial position. Hemimicropsia may thus be considered a limited violation of the size constancy principle. Behavioural and anatomical data are discussed in relation to the neural basis of visual object perception in humans.

Autopsy↗
PubMed1994

Spinal cord infarcts during long-term inhibition of nitric oxide synthase in rats.

BACKGROUND AND PURPOSE: Chronic hypertension is a major predisposing factor for stroke in humans. It has recently been shown that long-term inhibition of nitric oxide synthase activity causes a gradual time-dependent increase in arterial blood pressure in rats. We used this new animal model of chronic hypertension to study the occurrence and spatial features of infarcts in the central nervous system. METHODS: Rats were treated with a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, dissolved in the drinking water at 50 mg/kg per day for 11 weeks. The brains and spinal cords of hypertensive rats with and without motion disturbances were processed for standard microscopic examination. RESULTS: Seventy-nine percent of the hypertensive rats showed motion dysfunctions, especially front leg paralysis, and/or died suddenly when their systolic blood pressure reached approximately 215 mm Hg after approximately 7 weeks of treatment. All of the hypertensive rats with stroke had spinal cord infarcts (90% at the cervical or cervicothoracic level) either alone or combined with brain lesions (30%). These structural alterations ranged from focal areas of pale, spongy tissue to large necrotic sites with vascular alterations, including thickened or fibrinoid degenerated vessel wall, macrophage invasion, and reactive astrocytes. CONCLUSIONS: Infarcts occurred in the central nervous system with a high incidence in the spinal cord of hypertensive rats in which nitric oxide synthase was chronically blocked. This location of the hypertensive neuropathologic sequelae contrasts with the model of stroke-prone spontaneously hypertensive rats. The results suggest that nitric oxide is a key factor in spinal cord arteriolar vasomotion and structure in rats.

Amino Acid Oxidoreductases↗
PubMed1994

Isolated motor control dysfunction related to progressive multifocal leukoencephalopathy during AIDS with normal MRI.

We describe the case of a human immunodeficiency virus-infected 34-year-old man with progressive multifocal leukoencephalopathy (PML). His case displayed unusual features, including a bizarre movement disorder, predominant involvement of the subcortical U fibers on neuropathologic examination, and the absence of MRI abnormalities suggestive of PML. Anatomic-clinical correlations are discussed.

AIDS Dementia Complex↗
PubMed1994

[Intramedullary localization of a primary cerebral lymphoma in AIDS].

A 36 years-old male with AIDS, presented with left hemiparesis revealing a right parietal tumour. Stereotactic biopsy demonstrated a malignant non-Hodgkin's lymphoma. His condition partially improved following radiotherapy and chemotherapy. Three months later he was re-admitted with progressive bilateral root pain and urinary incontinence resulting in paraplegia with sensory loss below T10. He died one month later from generalized sepsis. Neuropathology confirmed an immunoblastic B-cell malignant non-Hodgkin's lymphoma in the white matter of the right parietal lobe and revealed a centrospinal localisation of the lymphoma in the thoracic cord at T10. There was no visceral localisation of the tumour. Secondary spread to the spinal cord of malignant non Hodgkin's lymphomas, usually causes meningo-myelo-radiculitis. Intraspinal deposits of primary cerebral lymphomas are uncommon and have never been previously described in AIDS, to our knowledge. Their pathogenesis is unclear. In our case, neuropathological findings are consistent with diffusion of the primary tumour to leptomeninges and secondary infiltration of the spinal cord along the perivascular spaces.

Adult↗
PubMed1994

Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV) latent infection and cerebral parenchymal infiltration during chronic lymphocytic leukemia.

We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV) cerebral co-infection. Multiple subcortical hypodensities lining the cortico-subcortical junction were present within the white matter on computerized tomography (CT) scan, with large areas of high signal intensity on T2-weighted sequences on magnetic resonance imaging (MRI). JCV DNA was identified in peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells with the same phenotype as leukemic blood cells were disseminated in the demyelinated areas. They were labeled by anti-latent membrane protein and by BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization. EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral reactivation of previously latent JCV infection with further development of simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.

B-Lymphocytes↗
PubMed1993

[Diagnosis of diffuse encephalopathies in adults with HIV infection. 2].

A variety of the central nervous system lesions may cause a diffuse encephalopathy in AIDS patients. Apart from viral encephalitides already described in part one, metabolic encephalopathies are a classical cause of diffuse brain dysfunction and are frequent at the terminal stage of the disease. Atypical forms of some infectious, vascular or tumoural processes which usually determine focal lesions, may cause diffuse encephalopathies. These forms are not exceptional in AIDS. The association in the same patient of lesions due to different agents is the rule. Whereas most of the neurological complications of AIDS occur late in the course of the disease, symptomatic, usually transient encephalopathies have been described in the early stages of HIV infection in rare cases. The authors conclude by proposing a management plan, since therapeutic advances have raised some hopes of improvement and even regression of some of these disorders in a few cases, so that physicians do not systematically give up when an AIDS patient presents with a diffuse encephalopathy.

AIDS-Related Opportunistic Infections↗
PubMed1993

[Diagnosis of diffuse encephalopathies in adults with HIV infection. I].

The diagnostic approach of focal central nervous system lesions in AIDS patients is now well established. In contrast, it is extremely difficult to determine the cause of diffuse encephalopathies, occurring frequently at the terminal stage of AIDS. Imaging is usually non specific and laboratory investigations are seldom contributive. In most cases, the aetiological diagnosis is provided by post mortem examination. In this first part of the study the authors deal with viral encephalitides which represent a classical and frequent cause of diffuse encephalopathy in AIDS. HIV encephalitis usually causes a progressive brain disease resulting in severe dementia; imaging may show diffuse leucoencephalopathy and/or cortico-subcortical atrophy. CMV encephalitis is often asymptomatic, discovered at autopsy; however, this diagnosis should be considered in patients with an encephalopathy of rapid onset, discrete signs of meningitis, symptoms of myelo-radiculitis, or a systemic CMV infection. Varicella-zoster virus encephalitis is not uncommon and may occur in the absence of characteristic rash. Infections by herpes simplex and measles viruses are exceptional.

AIDS Dementia Complex↗
PubMed1993

Crossed aphasia with visceral situs inversus.

A patient presenting the association of anomalous cerebral dominance for language, as revealed by crossed aphasia, and partial visceral situs inversus is described. Although it cannot be excluded that the two abnormalities coincided by chance, it is suggested that they both resulted from a single aberration of development.

Aged↗