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Biomedical subjects

B Doshi

Publications and source records attributed to B Doshi.

15 recordsLinked to original sources
PubMed2000

Comparative bioavailability study of clonazepam after oral administration of two tablet formulations.

OBJECTIVE: To assess the bioavailability of clonazepam from two brands of 2 mg tablet formulations--Epitril and reference brand. METHODS: A two-way randomised cross-over bioavailability study was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of clonazepam by high performance liquid chromatography (HPLC) method. RESULTS: The mean Cmax, Tmax t1/2 beta and AUC (0-48) for Epitril were: 16.31 +/- 3.07 ng/mL, 1.63 +/- 0.48 h, 46.97 +/- 12.26 h and 207.70 +/- 57.07 ng/ml.h; for reference brand were 19.75 +/- 5.95 ng/mL, 1.42 +/- 0.29 h, 46.88 +/- 11.29 h and 215.70 +/- 50.89 ng/ml.h respectively. These were comparable and the differences were not statistically significant. CONCLUSION: Based on above pharmacokinetic parameters, Epitril was bioequivalent to reference brand.

Administration, Oral↗
PubMed1999

Cytoskeletal pathology in familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation.

The histological features of familial cerebral amyloid angiopathy (British type) with non-neuritic amyloid plaque formation (FAB) include deposition of amyloid, (supposedly associated with the C-terminal fragments of both alpha- and beta-tubulin), in small cerebral and spinal arteries, hippocampal amyloid plaques and neurofibrillary tangles (NFTs) as well as ischaemic white matter changes. In the present study we report on the cytoskeletal pathology that occurs in association with FAB. Sections from the hippocampus and cerebellum of three cases from three unrelated families were stained with silver impregnation methods and antibodies to antigens including tau, neurofilaments, ubiquitin and glial fibrillary acidic protein. Electron microscopic examination of the hippocampus was carried out in one case. All hippocampal subregions contained large numbers of NFTs and neuropil threads (NT), which were stained with both phosphorylation-dependent and phosphorylation-independent tau antibodies and ultrastructurally were found to be composed of paired helical filaments (PHFs). Although the majority of the amyloid plaques were of the non-neuritic type, distended PHF-containing and tau-positive neurites were seen in close proximity of a minority of the hippocampal plaques. The perivascular amyloid deposits of the cerebellum contained numerous ubiquitin-positive granular elements similar to those seen in cerebellar A beta amyloid plaques in Alzheimer's disease. In FAB severe cytoskeletal pathology is present in areas most affected by amyloid plaque deposits, thus suggesting a localised neurotoxic effect of the poorly characterised amyloidogenic peptide characteristic of this condition.

Biomarkers↗
PubMed1997

Alterations in hippocampal non-phosphorylated MAP2 protein expression in schizophrenia.

Microtubule-associated proteins (MAPs) are central to the development of normal neuronal cytoarchitecture and have been suggested in previous studies to be altered in schizophrenia. We investigated hippocampal phosphorylated and non-phosphorylated MAP2 expression in schizophrenia in relation to neuronal orientation and interneuronal distance. One paraffin embedded mid-hippocampal block was obtained from each of 8 schizophrenic and 11 control postmortem brains and immunohistochemistry for the phosphorylated and non-phosphorylated forms of MAP2 performed. Within the corona ammonis (CA) subregions and the subiculum, we assessed densitometry readings for non-phosphorylated MAP2-positive neurones (MAP2-NP), and counted the number of neurones immunopositive for phosphorylated MAP2 (MAP2-P). Using image analysis computer software we measured interneuronal distances and neuronal orientation. While there were no overall alterations in densitometric density of MAP2-NP neurones in any hippocampal subregions, we found a left-sided increase in densitometric density of MAP2-NP neurones within the subiculum (F = 8.740, P < 0.021), and the CA1 (F = 7.044, P < 0.033) of schizophrenic subjects which were unrelated to age, postmortem interval or neuroleptic exposure. There was no accompanying alteration of interneuronal distances, neuronal orientation. The findings support previous work demonstrating altered subicular MAP2 expression in schizophrenia and indicate that the finding may be lateralised. However, in contrast to previous investigations, we have demonstrated this alteration in MAP2 expression is due to an increase in the non-phosphorylated form of MAP2, rather than a decrease in total MAP2 expression. These findings suggest that cytoskeletal assembly is abnormal in schizophrenia and generate testable hypotheses regarding the developmental basis of the disorder.

Adult↗
PubMed1995

Medullary cell carcinoma of the thyroid: metastases to the central nervous system.

We document a case of a patient who had been treated for a medullary cell carcinoma of the thyroid three years previously and who presented with a three month history of ataxia, weakness and headache. A CT scan showed contrast enhancing lesions in the posterior fossa. An MIBG uptake scan showed that there was some uptake in the cerebellar lesions; however, it was not sufficient to rely on this alone for treatment. The larger of these lesions was therefore surgically resected. Immunocytochemistry, using CAM 5.2, CEA and chromogranin, demonstrated a positive reaction which strongly favoured a diagnosis of metastases from a medullary cell carcinoma of the thyroid. However, absolute confirmation of the diagnosis was obtained using immunocytochemistry with calcitonin. Medullary cell carcinomas of the thyroid usually spread locally and metastasis to the brain has never before been reported.

Aged↗
PubMed1995

Perils of a 'true' posterior communicating artery aneurysm.

Successful 'clipping' of the apparent neck of a posterior communicating artery aneurysm was carried out, but 2 days later the patient had a further haemorrhage and died. Postmortem examination revealed that the aneurysm was that of a rare fusiform 'true' posterior communicating artery aneurysm.

Aged↗
PubMed1994

Delayed cerebral ischaemia: the pathological substrate.

Ischaemic complications both at the level of the cortex and the hypothalamus are well recognised after an aneurysmal subarachnoid haemorrhage. We have studied histological changes in the cortex (53 patients) and hypothalamus (48 patients) in patients who died after an aneurysmal subarachnoid haemorrhage. Cortical ischaemic lesions were demonstrated in 41 of the 53 patients studied. These changes were more common in patients who had impaired control of systemic blood pressure (p = 0.0004) and in patients who died gradually (p = 0.0003). Hypothalamic lesions were found in 24 of 48 patients studied; 23 of these patients had widespread associated changes in the cerebral cortex. Patients with moderate/severe cortical changes tended to have hypothalamic lesions and it was uncommon for patients with no cortical lesions to have changes in the hypothalamus (p = 0.0007). We believe that these histological changes are due to diffuse microangiopathy which develops slowly after a subarachnoid haemorrhage and affects the cortex and hypothalamus. Because the cortical lesions are widespread we postulate that they may be implicated in the aetiology of the well described psychosocial or cognitive problems in patients who survive a subarachnoid haemorrhage.

Adult↗
PubMed1991

Malignant glioma in laboratory workers.

In 1989 an increased risk of cancer, with a higher than expected incidence of brain tumours, was reported in laboratory workers at the Pasteur Institute, Paris. Three cases of primary brain tumours occurring in three laboratory workers from one laboratory in a district general hospital also came to light. Although this may have been due to coincidence or geographic clustering, the need for stringent safety standards in all laboratories is reiterated, and it is proposed that a national register should be established to record the causes of death in laboratory workers.

Adult↗
PubMed1986

Primary intracranial choriocarcinoma.

Two cases of primary intracranial choriocarcinoma are reported. One patient died with raised intracranial pressure and pulmonary metastases whereas the second patient, who was diagnosed early, has remained well a year after chemotherapy. Human chorionic gonadotrophin level estimation in serum and cerebrospinal fluid is a useful marker in suspected cases, and chemotherapy following biopsy appears to be the treatment of choice.

Adolescent↗
PubMed1981

Some patients with cerebral aneurysms are deficient in type III collagen.

Polyacrylamide gel electrophoresis of pepsin-digested skin biopsy specimens and carboxymethyl cellulose chromatography of radioactively labelled collagens produced by cultured fibroblasts demonstrated that 7 of 12 patients with congenital cerebral aneurysms were type III collagen deficient. This suggests that some cerebral aneurysms resemble various inherited defects of connective tissue-i.e., Ehlers-Danlos syndrome type IV-in which type III collagen deficiency causes arterial fragility.

Cerebral Hemorrhage↗
PubMed1979

Cerebral malaria in the United Kingdom.

Four fatal cases of cerebral Plasmodium falciparum malaria in English travellers returning from Africa have been seen in the last 13 years. The haemorrhages, accumulations of microglia, and destruction of cerebral white matter around small veins as a result of blockage of cortical capillaries by parasitised red blood corpuscles resemble the effect of fat embolism. Microglia in the lesions is demonstrated by special neuropathological techniques. Attention is drawn to the need for a prompt recognition of malaria since appropriate treatment can be successful.

Adult↗
PubMed1978

Effect of propranolol and phentolamine on myocardial necrosis after subarachnoid haemorrhage.

A study was set up to assess the effect on the clinical course of subarachnoid haemorrhage (SAH) of giving propranolol 80 mg eight-hourly plus phentolamine 20 mg three-hourly by mouth for three weeks. Out of the 90 patients studied, 14 died. Two of the deaths occurred in an open pilot study of 10 patients, the remaining 12 deaths occurring in patients in a randomised double-blind placebo-controlled study. Postmortem examination was carried out on 12 of the patients, six of whom had been receiving placebo and six propranolol plus phentolamine. Necrotic myocardial lesions were present in the hearts of all six patients (age range 30-59 years) who died while taking placebo (all had had abnormal electrocardiograms (ECGs). In contrast, no necrotic lesions were found in the hearts of the six patients (age range 28-59) who died while receiving the drugs (all had previously had normal ECGs). We conclude that the necrotic myocardial lesions were induced by catecholamines and that propranolol had a cardioprotective effect. While death from a further haemorrhage in cases of SAH is not affected by propranolol and phentolamine, propranolol may have a beneficial effect in other potentially lethal stresses.

Adult↗