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Biomedical subjects

A Mehta

Publications and source records attributed to A Mehta.

At least 235 records · Page 13Linked to original sources
PubMed1990

Potency and selectivity of the non-steroidal aromatase inhibitor CGS 16949A in postmenopausal breast cancer patients.

A selective inhibitor of aromatase is widely sought for the treatment of postmenopausal women with breast cancer. CGS 16949A has been shown to be a highly selective, potent inhibitor of aromatase in vitro. Its potency as an oestrogen suppressant and its selectivity were examined by treating 24 postmenopausal patients with advanced breast cancer for 4 weeks with doses of 0.3, 1.0 and 2.0 mg twice daily. The study was conducted in two parts which compared the two lower doses and the two higher doses separately in a cross-over design protocol. All doses significantly suppressed serum oestradiol and oestrone levels below pretreatment levels. Cross-over analysis indicated that the 2.0 mg twice daily dose achieved significantly greater suppression of oestradiol levels than 0.1 mg twice daily but there was no significant differences between any of the doses in the suppression of oestrone. No significant effects were noted on serum levels of LH, FSH, SHBG, prolactin, testosterone, androstenedione, 17-hydroxyprogesterone or cortisol. For the four steroids this was true both for basal samples and those collected after Synacthen stimulation. However, serum aldosterone levels were significantly suppressed by 1.0 mg twice daily CGS 16949A and further suppressed by 2.0 mg twice daily. It is concluded that CGS 16949A is a potent oestrogen suppressant in postmenopausal patients but that its effect is not totally selective.

Aged↗
PubMed1990

Nucleolar organizer regions in gastric carcinoma and its precursor stages.

A silver technique for nucleolar organizer regions (AgNOR) was applied to sections from 156 gastric biopsies and gastrectomy specimens. These included normal controls, normal gastric mucosa from carcinoma-bearing stomachs, intestinal metaplasia types I and III, dysplasia and carcinoma. AgNOR counts gradually increased from normal, through intestinal metaplasia, to carcinoma. This finding supports the chronic atrophic gastritis-intestinal metaplasia-dysplasia-carcinoma sequence concept for gastric carcinogenesis. Normal gastric mucosa was different from all lesions, including normal mucosa from carcinoma-bearing stomachs. Significantly higher AgNOR counts were observed in tumours compared to all other lesions except dysplasia. Dysplasia differed from intestinal metaplasia type I but not from type III. Eighty-five per cent of metaplasia cases overlapped with carcinoma and 19% with normal controls. The spread of AgNOR values in intestinal metaplasia reinforces the concept that this lesion is a heterogeneous entity reflecting a dynamic and continuous process. The AgNOR technique may contribute to the assessment of the stage of evolution of 'borderline' lesions.

Biopsy↗
PubMed1990

The effects of steroid therapy on pulmonary hypertension secondary to fibrosing mediastinitis.

Mediastinal fibrosis, a rare cause of pulmonary hypertension, may produce cough, dyspnea, and hemoptysis. Steroid therapy has been suggested for individuals with progressive symptoms, but data demonstrating the efficacy of such therapy are lacking. We present a case of pulmonary hypertension secondary to fibrosing mediastinitis. Hemodynamic and scintigraphic studies performed before and after a trial of corticosteroid therapy were unable to demonstrate any therapeutic benefit from the corticosteroids. In order to achieve better use of steroids for the treatment of this disease, we suggest that similar determinations be made on other patients with mediastinal fibrosis who receive such treatment.

Adult↗
PubMed1989

Spectral diagnosis of atherosclerosis using an optical fiber laser catheter.

This communication demonstrates that fluorescence spectra of human aorta with good S/N ratios can be collected using an optical fiber laser catheter. The performance of this catheter is compared to a non-fiber optic collection system with an equivalent delivery/collection geometry. For a given sample, fluorescence lineshapes obtained using the two systems are identical; differences in peak fluorescence intensity are related to the different collection efficiencies of the two systems. It is shown that the fluorescence lineshape of arterial tissue depends on the delivery/collection geometry of the detection system, and that this is due to the interaction of absorption and fluorescence within the artery wall. This effect is investigated systematically using a specially designed collection system. Results are analyzed qualitatively using a simple, one-dimensional model of tissue fluorescence. With this analysis, we present design requirements for a collection system in which such geometric effects are eliminated, and show that our optical fiber laser catheter satisfies these requirements.

Aortic Diseases↗
PubMed1989

High doses of caffeine impair performance of a numerical version of the Stroop task in men.

The effects of caffeine ingestion on mid-morning cognitive performance were investigated in thirty-two male subjects. These were given drinks containing either no caffeine, 125 mg caffeine (mean dose: 1.38 mg/kg), or 250 mg caffeine (mean dose: 3.45 mg/kg) and were tested on three tasks: 1) free recall of supraspan word lists, 2) a response time (pointing) task and 3) a numerical Stroop task. There were no significant group differences on the recall task or in response times, but subjects having the higher caffeine dose were seriously impaired on the Stroop test, making particularly slow responses. Caffeine may have a deleterious effect on the rapid processing of ambiguous or confusing stimuli, and this may account for its clear effect on the Stroop test than on other cognitive tests used hitherto.

Adult↗
PubMed1988

Brain hexokinase has no preexisting allosteric site for glucose 6-phosphate.

Difference spectroscopic investigations on the interaction of brain hexokinase with glucose and glucose 6-phosphate (Glc-6-P) show that the binary complexes E-glucose and E-Glc-6-P give very similar UV difference spectra. However, the spectrum of the ternary E-glucose-Glc-6-P complex differs markedly from the spectra of the binary complexes, but resembles that produced by the E-glucose-Pi complex. Direct binding studies of the interaction of Glc-6-P with brain hexokinase detect only a single high-affinity binding site for Glc-6-P (KD = 2.8 microM). In the ternary E-glucose-Glc-6-P complex, Glc-6-P has a much higher affinity for the enzyme (KD = 0.9 microM) and a single binding site. Ribose 5-phosphate displaces Glc-6-P from E-glucose-Glc-6-P only, but not from E-Glc-6-P complex. It also fails to displace glucose from E-glucose and E-glucose-Glc-6-P complexes. Scatchard plots of the binding of glucose to brain hexokinase reveal only a single binding site but show distinct evidence of positive cooperativity, which is abolished by Glc-6-P and Pi. These ligands, as well as ribose 5-phosphate, substantially increase the binding affinity of glucose for the enzyme. The spectral evidence, as well as the interactive nature of the sites binding glucose and phosphate-bearing ligands, lead us to conclude that an allosteric site for Glc-6-P of physiological relevance occurs on the enzyme only in the presence of glucose, as a common locus where Glc-6-P, Pi, and ribose 5-phosphate bind. In the absence of glucose, Glc-6-P binds to the enzyme at its active site with high affinity. We also discuss the possibility that, in the absence of glucose, Glc-6-P may still bind to the allosteric site, but with very low affinity, as has been observed in studies on the reverse hexokinase reaction.

Adenosine Triphosphate↗
PubMed1988

Disposition of ifosfamide in patients receiving ifosfamide infusion therapy for the treatment of cervical carcinoma.

The disposition of ifosfamide was investigated in nine patients receiving a total of 23 72-h infusions. There was no linear relationship between steady-state plasma concentrations and either vomiting or CNS toxicity. The steady-state plasma concentrations were reproducible within patients, but there was a wide variation between patients. The progress of the disease did not affect the disposition of ifosfamide.

Female↗
PubMed1988

High temperature storage of potato (Solanum tuberosum L.) for processing--a feasibility study.

Tubers of three potato cultivars were stored at room temperature (20-39 degrees C, 30-75% RH), under an insulated storage run on passive evaporative cooling (16-30 degrees C, 70-90% RH) and a refrigerated storage (2-4 degrees C, 90-95% RH) for 14 weeks and studied periodically for storage losses, reducing sugar content and dry matter percent of tubers, in order to explore the possibility of storing potatoes for processing at higher temperatures. Physiological losses in tubers remained less than 10% until 12 weeks of storage under evaporatively cooled storage. Reducing sugar contents increased by only 52.4-242.1% in tubers stored in evaporatively cooled storage as compared to 90.5-484.2% increase in tubers stored in refrigerated storage until 14 weeks. Potatoes stored in evaporatively cooled store were more suitable for processing into chips and french fries due to lower physiological losses and lower reducing sugar content of tubers.

Feasibility Studies↗
PubMed1988

Peptide histidine methionine (PHM) increases ileostomy output.

The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PHM) which has substantial sequence homology with VIP. Both are present in nerve fibers in the human ileum and circulate in greatly increased concentrations in patients with the watery diarrhoea syndrome. We have infused PHM (23 pmol/kg/min) into 5 patients with ileostomies to determine the effect of PHM on human ileal output. Plasma PHM levels rose from 22 +/- 6 to 6013 +/- 874 pM (mean +/- S.E.M.) during PHM infusions and ileal output rose from 16 +/- 3 to 177 +/- 27 g/30 min (P less than 0.0001). PHM infusions also produced a significant fall in the percentage of solid material and a rise in the concentration of chloride in the ileal effluent. Mean plasma PHM concentrations during PHM infusions were equal to the highest levels seen in patients with the watery diarrhoea syndrome, so PHM may contribute to diarrhoea in this condition. Neuronal PHM may exert physiological control over ileal transport of water and electrolytes.

Chlorides↗
PubMed1988

Spinal cord cultured neurons: an in vitro model to study GABA synaptic pharmacology.

In summary, spinal cord cultured neurons provide an in vitro model for studying GABA synaptic pharmacology. GABAA agonists stimulate 36Cl-influx in these cells in a concentration-dependent manner. The enhancing effect of GABA is potentiated by BZ agonists, inhibited by GABA antagonists, and attenuated by the inverse agonist beta-carboline, DMCM. These cells also exhibit the specific binding of [3H]flunitrazepam with a pharmacological specificity of the central BZ receptors. Finally, BZ receptors are coupled to GABA, barbiturate, and picrotoxin sites in these cells, as indicated by allosteric interactions both by binding and 36Cl-influx assay.

Animals↗