Search PubMed⌕ Search

Biomedical subjects

R Doshi

Publications and source records attributed to R Doshi.

At least 19 recordsLinked to original sources
PubMed1998

PCNA and Ki-67 labelling indices in pre-irradiated and post-irradiated astrocytomas: a comparative immunohistochemical analysis for evaluation of proliferative activity.

AIM: To determine the tumour proliferative activity in a series of archival cerebral astrocytomas and compare proliferating cell nuclear antigen (PCNA) and Ki-67 labelling indices in the primary and recurring neoplasms following therapeutic radiation. METHOD: Twenty eight cases of pre-irradiated and post-irradiated astrocytomas (ranging from WHO grades I to IV) were stained immunohistochemically using the avidin-biotin horseradish peroxidase technique. Two antibodies, PC10 and MIB-1, were used to establish the proliferating labelling indices, PC10 identifies PCNA and MIB-1 recognises the Ki-67 antigen. RESULTS: Both antibodies showed significantly higher labelling indices in the post-irradiated specimens. However, in general, the Ki-67 indices were lower than those for PCNA. MIB-1 immunoreactivity showed less variation and was more intense than that seen with PC10. The discrepancy between the labelling indices of the pre-irradiated and post-irradiated samples raises questions about the evolution of astrocytomas and the effects of therapeutic intervention. CONCLUSIONS: The data may represent genetic alterations, the natural tumour course, and/or the effect of radiation. Although both of the antibodies reflected the state of growth of neoplastic cells in astrocytomas, MIB-1 was more reliable. A simple immunohistochemical method using proliferation markers does have an important role in the future care of patients with astrocytoma.

Adult↗
PubMed1996

Metastatic cerebral choriocarcinoma coexistent with a viable pregnancy.

Gestational choriocarcinoma associated with a viable pregnancy is extremely rare, and such choriocarcinoma with metastases presenting during the pregnancy is even more exceptional. Metastases from this tumor may present in a variety of ways depending on the site of the metastatic lesion, and can be fatal before choriocarcinoma is even suspected. We describe a 32-year-old primigravida presenting at 31 weeks gestation with a grand mal seizure due to cerebral metastases secondary to gestational choriocarcinoma who was subsequently successfully treated with chemotherapy. To our knowledge this is the first reported case of choriocarcinoma presenting with signs due to cerebral metastases during pregnancy where both the mother and child survived. This paper emphasizes the need to consider metastatic choriocarcinoma in any gravid female who presents with unusual neurological signs because of the life-threatening nature of this potentially curable disease.

Adult↗
PubMed1996

Mechanisms of injury-induced calcium entry into peripheral nerve myelinated axons: role of reverse sodium-calcium exchange.

To investigate the route of axonal Ca2+ entry during anoxia, electron probe x-ray microanalysis was used to measure elemental composition of anoxic tibial nerve myelinated axons after in vitro experimental procedures that modify transaxolemmal Na+ and Ca2+ movements. Perfusion of nerve segments with zero-Na+/Li(+)-substituted medium and Na+ channel blockade by tetrodotoxin (1 microM) prevented anoxia-induced increases in Na and Ca concentrations of axoplasm and mitochondria. Incubation with a zero-Ca2+/EGTA perfusate impeded axonal and mitochondrial Ca accumulation during anoxia but did not affect characteristic Na and K responses. Inhibition of Na(+)-Ca2+ exchange with bepridil (50 microM) reduced significantly the Ca content of anoxic axons although mitochondrial Ca remained at anoxic levels. Nifedipine (10 microM), an L-type Ca2+ channel blocker, did not alter anoxia-induced changes in axonal Na, Ca, and K. Exposure of normoxic control nerves to tetrodotoxin, bepridil, or nifedipine did not affect axonal elemental composition, whereas both zero-Ca2+ and zero-Na+ solutions altered normal elemental content characteristically and significantly. The findings of this study suggest that during anoxia, Na+ enters axons via voltage-gated Na+ channels and that subsequent increases in axoplasmic Na+ are coupled functionally to extraaxonal Ca2+ import. Intracellular Na(+)-dependent, extraaxonal Ca2+ entry is consistent with reverse operation of the axolemmal Na(+)-Ca2+ exchanger, and we suggest that this mode of Ca2+ influx plays a general role in peripheral nerve axon injury.

Animals↗
PubMed1995

Mechanisms of injury-induced calcium entry into peripheral nerve myelinated axons: in vitro anoxia and ouabain exposure.

In the present investigation, electron probe X-ray microanalysis was used to characterize the effects of in vitro ouabain (2 mM) or anoxia on elemental composition (e.g. Na, K, Ca) and water content of rat peripheral (tibial) nerve myelinated axons and Schwann cells. Results showed that independent of axon size, both ouabain and anoxia markedly increased axoplasmic Na and decreased K concentrations. However, only anoxia was associated with significant elevation of axonal Ca content. Mitochondrial areas from ouabain- or anoxia-exposed fibers exhibited changes in element and water contents that were similar to axoplasmic alterations. Schwann cells and myelin displayed small increases in Na and substantial losses of K in response to ouabain exposure. In contrast, these glial compartments were relatively resistant to anoxia as indicated by the modest and delayed nature of the elemental changes. Nonetheless, neither treatment significantly affected glial Ca concentrations. Our results suggest that Ca2+ accumulation in peripheral nerve axons is complex and involves not only deregulation of Na+ and K+ but other fundamental pathogenic changes as well. In addition to providing baseline information, we have identified an in vitro model (anoxia) which features Ca2+ build-up in PNS myelinated axons. Thus, the present study offers a foundation for investigation into mechanisms of Ca2+ entry following peripheral nerve injury.

Animals↗
PubMed1994

Postmortem brains reveal similar but not identical amyloid precursor protein-like immunoreactivity in Alzheimer compared with other dementias.

Concentrations of amyloid precursor protein (APP)-like immunoreactivity (APPLIR) have been determined by Western blotting in a soluble fraction and two membrane fractions of two areas of brain cortex from patients with Alzheimer's disease (AD) and other dementias. There were no significant differences between AD and other cases in species with the Kunitz protease inhibitor domain. However, the total soluble APPLIR was higher in AD and it was hypothesized that this relates to cholinergic hypoactivity.

Aged↗
PubMed1994

beta-Amyloid precursor protein isoforms show correlations with neurones but not with glia of demented subjects.

Post-mortem cerebral cortex from 15 demented patients was specially collected to minimise autolysis and two membrane fractions and one soluble fraction were quantitatively examined for the major species of beta-amyloid precursor protein (APP) of high apparent molecular mass (> or = 80 kDa) together with the major mRNA species encoding APP isoforms. The number of pyramidal neurones and astrocytes, putative biochemical indices of interneurones and pyramidal neurones, and choline acetyl transferase activity were also determined. Multiple regression analysis has been used to investigate intercorrelations of APP species with biochemical and morphometric measures, free of any effects of confounding demographic variables. Subjects with Alzheimer's disease showed a loss of cholinergic activity and D-aspartate uptake compared with patients with other causes of dementia. The major finding of the study is that measures of neurones rather than astrocytes most closely correlate with the concentration of APP. Pyramidal cell numbers were positively correlated with mRNA for APP695. APP in the soluble fraction showed a negative correlation with pyramidal cell numbers and cholinergic activity. These results indicate that neurones within the cerebral cortex are the major source of APP, and that secretion of APP is dependent upon cortical pyramidal neuronal activity and cholinergic activity.

Aged↗
PubMed1994

Detection of antibodies to defined M. tuberculosis antigen (38 kDa) in cerebrospinal fluids of patients with tuberculous meningitis.

Antibodies to the 38 kDa antigen of M. tuberculosis which is serospecific to the tuberculosis complex group of organisms was studied in CSF samples of patients with tuberculosis meningitis. Patients were classified into four groups, viz. post-mortem-proved, culture-proved, clinically suspected and tuberculoma. Anti-38 kDa antibody was detected by ELISA and was positive in 60%, 80% 62.5% and 0%, respectively in the four groups. Controls showed a false-positive detection of 5%. Follow-up of patients was done up to 6 weeks and antibody levels dropped in all the patient groups.

Antibodies, Bacterial↗
PubMed1993

Calculation of volume flow rate by the proximal isovelocity surface area method: simplified approach using color Doppler zero baseline shift.

OBJECTIVES: The goal of this study was to develop an accurate, simplified proximal isovelocity surface area (PISA) method for calculating volume flow rate using lower blue-red interface velocity produced by a color Doppler zero baseline shift technique. BACKGROUND: The Doppler color proximal isovelocity surface area method has been shown to be accurate for calculating the volume flow rate (Q) across a narrowed orifice by the formula Q = PISA x Blue-red interface velocity. A hemispheric model is generally used to calculate proximal isovelocity surface area (PISA = 2 pi a2, where a = the radius corresponding to the blue-red interface velocity). Although a hemispheric model is simple, requiring measurement of one radius, it may underestimate the actual volume flow rate because, in the general case, the shape of a proximal isovelocity surface area is hemielliptic. Although a hemielliptic model is generally more accurate for calculating proximal isovelocity surface area, it is more complex, requiring measurement of two orthogonal radii. METHODS: Sixteen in vitro constant flow model studies were performed using planar circular orifices (diameter range 6 to 16 mm). The blue-red interface velocity was changed from 3 to 54 cm/s using color Doppler zero baseline shift. RESULTS: 1) With decreasing blue-red interface velocity, the size of the proximal isovelocity surface area was increased, and its shape changed from hemielliptic to hemispheric. 2) With the blue-red interface velocity in the range 11 to 15 cm/s, the proximal isovelocity surface area became nearly hemispheric; however, it was difficult to determine the blue-red interface radius at a blue-red interface velocity < 10 cm/s because of interface fluctuations. 3) Calculated volume flow rate using the hemispheric proximal isovelocity surface area model with a single radius was relatively accurate at a blue-red interface velocity of 11 to 15 cm/s (mean percent difference from actual volume flow rate was -3.6%). CONCLUSIONS: Because the shape of the proximal isovelocity surface area is nearly hemispheric at a blue-red interface velocity of 11 to 15 cm/s, volume flow rate can be accurately calculated in this proximal isovelocity surface area interface velocity range (produced by zero baseline shift) by measuring a single-interface radius. This approach should be clinically useful for calculating the volume flow rate across stenotic and regurgitant valves and across shunt defects.

Blood Flow Velocity↗
PubMed1992

Can signal intensity of the continuous wave Doppler regurgitant jet estimate severity of mitral regurgitation?

Visual estimates of the intensity of the continuous wave (CW) Doppler regurgitant jet signal have been used to estimate the severity of valvular regurgitation. Theoretically, the strength of the reflected Doppler signal is a function of the number of scatterers. To test this approach quantitatively, free jets were produced in 27 experiments using a power injector and cornstarch suspension varying in concentration from 1% to 3%. Flow volume was varied from 5 to 15 ml, and orifice diameter varied from 2.5 to 10 mm. Machine settings were kept constant. Also, 22 patients with mitral regurgitation (MR)--5 mild, 11 moderate, and 6 severe by angiography--were studied. Average signal intensity under the CW Doppler flow curve was calculated using a computer image processor. In MR patients, average regurgitant flow (RF) intensity was compared with average mitral forward flow (FF) signal intensity. (1) The intensity under the CW flow signal in the free jet experiments correlated well with injection volume (r greater than 0.98). (2) RF average signal intensity did not correlate with angiographic MR severity (r = 0.21), but the ratio of RF to FF average signal intensity did correlate with MR severity (r = 0.73). (3) The sensitivity and the specificity of an RF/FF ratio greater than 0.65 for angiographically severe mitral regurgitation were both 83%. (4) The sensitivity and specificity of an RF/FF ratio less than 0.50 for angiographic mild mitral regurgitation were both 80%. The ratio of regurgitant to forward mitral flow CW Doppler signal intensity appears to be an accurate and clinically applicable method for estimating the severity of mitral regurgitation.

Adult↗
PubMed1992

Transcriptional regulation of left ventricular beta-adrenergic receptors during chronic hypoxia.

beta-Adrenergic receptor downregulation is the end result of cellular adaptation to prolonged agonist exposure. The factors mediating receptor downregulation include receptor phosphorylation, receptor movement from the plasma membrane to intracellular sites, and alterations in nascent receptor synthesis. We have previously demonstrated a downregulation of the left ventricular beta-receptor during chronic hypoxia in vivo. To determine the mechanism of this downregulation, we produced chronic hypoxia in seven newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 weeks. Six lambs served as normoxic controls. Sarcolemmal membrane and cytosolic fractions were prepared from left ventricular free wall samples. beta-Receptor density in each fraction was determined with the radioligand [125I]iodocyanopindolol. Steady-state levels of beta-receptor mRNA were determined by Northern blot analysis using a beta 1-adrenergic receptor cDNA probe. During chronic hypoxia, left ventricular membrane beta-adrenergic receptor density decreased by 55% (153 +/- 28 fmol/mg for hypoxic lambs versus 342 +/- 79 fmol/mg for control lambs, p < 0.05). There was no corresponding increase in beta-receptor density in the cytosolic fraction (23 +/- 3 fmol/mg for hypoxic lambs versus 33 +/- 9 fmol/mg for control lambs, p = NS), nor was there a significant change in the ratio of beta 1-receptor/beta 2-receptor subtypes as assessed by radioligand binding (beta 1 subtype, 84.1 +/- 10.1% for hypoxic lambs versus 93.2 +/- 8.8% for control lambs; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Venous occlusion secondary to subluxation of the shoulder--a case report.

This is the case report of an eighty-seven-year-old woman who was seen because of swelling of her left upper extremity and breast of one week's duration. She had a history of severe arthritis of the knees and had been wheelchair-bound for seven years. Venography showed compression of the cephalic vein and thrombosis of the distal basilic vein with extension into the axillary and subclavian veins. To the author's knowledge, this is the first case report of venous thrombosis in association with subluxation of the shoulder.

Aged↗