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Biomedical subjects

A Mehta

Publications and source records attributed to A Mehta.

At least 253 records · Page 14Linked to original sources

A phase 2 study of surveillance in patients with metastatic renal cell carcinoma and assessment of response of such patients to therapy on progression.

Following preliminary studies suggesting that some patients with metastatic renal cell carcinoma had accelerated tumor growth after entry into chemotherapy studies, 73 patients with measurable metastatic disease referred to a tertiary referral center for consideration for experimental treatment protocol have been observed to attempt to establish the incidence of spontaneous regression. Initially, patients went off study if metastases showed greater than 25% increase in products of bidimensional measurement but with increasing confidence patients only went into therapy protocols with the development of symptomatic progression. In this selective series, on observation, three complete (histologically documented) and two partial unexplained "spontaneous" regressions were observed and a further four patients had prolonged stable disease for more than 12 months. On progression, 52 were entered into treatment protocols (BCG n = 19, Mitozantrone n = 12, and Welferon n = 21). A further two complete and five partial responses (14%) and four prolonged stable disease were observed confirming that the previously reported responses with these agents are not totally explicable on the basis of "spontaneous" response.

BCG Vaccine↗

Neurotensin and cholecystokinin coexistence within neurons of the ventral mesencephalon: projections to forebrain.

The colocalization of neurotensin- and cholecystokinin-like immunoreactivities was demonstrated in neurons of the ventral mesencephalon of the rat by using a double-labeling indirect immunofluorescence procedure for the simultaneous detection of two antigens in the same tissue section. Greater than 90% of the neurotensin-positive perikarya distributed throughout the ventral midbrain (primarily located in the ventral tegmental area, medial substantial nigra, and rostral and caudal linear raphe nuclei) were found to also contain cholecystokinin immunoreactivity. Neurons single-labeled for either peptide were also present, with those immunoreactive for cholecystokinin alone far outnumbering those containing only neurotensin. By combining the double-labeling colocalization technique with fluorescence retrograde tracing, some of the forebrain projections of these neurons were determined. Ventral mesencephalic neurons containing both neurotensin and cholecystokinin were found to project to the nucleus accumbens, prefrontal cortex, or amygdala. The present results, combined with those of previous studies, suggest that there are complex heterogeneous subpopulations of presumed dopaminergic ventral mesencephalic neurons which give rise to the ascending mesotelencephalic systems and which may contain both neurotensin and cholecystokinin, either peptide alone, or neither of these two peptides.

Animals↗

Effects of the gamma-aminobutyrate transaminase inhibitors gabaculine and gamma-vinyl GABA on gamma-aminobutyric acid release from slices of rat cerebral cortex.

The release of [3H]gamma-aminobutyric acid (GABA) from pre-loaded slices of rat cerebral cortex was investigated in the presence and absence of the GABA-transaminase inhibitors gabaculine and gamma-vinyl GABA. In the experiments carried out without an inhibitor, an ion-exchange column chromatographic technique was used to separate [3H]GABA from tritiated metabolites released with it into the superfusate. The presence of gabaculine (5 microM) substantially reduced the Ca2+-dependence of the release of [3H]GABA evoked by a 4 min 30 mM K+ pulse, whereas this was not appreciably reduced by the presence of gamma-vinyl GABA (2 mM or 10 mM). Nevertheless, the characteristics of [3H]GABA release were not identical in the presence and absence of either inhibitor.

4-Aminobutyrate Transaminase↗

Glycation of platelet protein in diabetes mellitus: lack of correlation with platelet function.

The relationship of nonenzymatic glycation of platelet proteins to altered platelet function was studied in 33 diabetic patients. Platelets isolated from diabetic patients were glycated to a greater extent than those isolated from nondiabetic controls. No relationship was found between the level of glycation of platelets in diabetics to parameters commonly used to monitor glycemic control (glycated hemoglobin, glycated albumin, fasting blood glucose). Platelets isolated from diabetics did not show an increased level of aggregation and Thromboxane B2 production as compared to nondiabetic controls. No significant relationship was found between the level of glycation and percent aggregation of platelets. The lack of a relationship between glycation and aggregation suggests that the former may not be responsible for the functional changes in platelets seen in diabetics.

Blood Glucose↗

Non-enzymatic glycation and altered renal structure and function in the diabetic rat.

Renal functional parameters including creatinine clearance, urinary albumin excretion, basement membrane thickening, and levels of non-enzymatic glycation of glomerular basement membrane were studied in rats rendered diabetic with streptozotocin. Diabetic animals had elevated, glycated hemoglobin levels (P less than 0.05), increased creatinine clearance, and urinary albumin excretion rates (P less than 0.05) as compared to insulin treated diabetic (euglycemic), age-matched, and streptozotocin non-diabetic animals. The level of non-enzymatic glycation of glomerular basement membrane was significantly elevated (P less than 0.05) in the diabetic animals as well, with the level of non-enzymatic glycation of all animals, correlating (P less than 0.05) to the average blood glucose level of each animal. Despite changes in functional parameters, and increased levels of non-enzymatic glycation between the diabetic and euglycemic animals, there was no difference in glomerular basement membrane thickness between the two groups. However, there was a difference between all diabetic euglycemics and the age-matched control animals. We hypothesize that increased glycation of glomerular basement membrane may alter renal function, possibly by affecting the net charge of the glomerular filtration barrier. However, glomerular basement membrane thickening per se does not affect the functional changes which have been observed, thus casting doubt upon its role in the development of diabetic nephropathy.

Animals↗

A comparison in neonatal piglets of model-dependent and model-independent methods for measuring glucose turnover.

Steady state glucose turnover was measured in 53 conscious, unrestrained neonatal piglets by two different methods using 3H-labelled glucose as the tracer. In the first, model-dependent method, the plasma tracer concentrations following a spike injection of tracer were fitted in various different ways and the turnover was calculated from the area under the fitted curve extrapolated to infinity. Both exponential curves and negative power functions of time were fitted by non-linear least squares. In the second, model-independent method, tracer was infused continuously and turnover calculated from its equilibrium concentration. Conditions during 34 of the 53 experiments failed various tests of the steady state and the data were therefore discarded. In the remaining 19, glucose turnover measured by the different methods agreed fairly well. Although there was little difference between the results obtained by a two-exponential curve fit, by those obtained when the fast component was ignored, by a single exponential curve fit, and by the results from fitting a negative power function of time, the conventional two-exponential curve is to be preferred. There was a suggestion that at high turnover rates, the injection result underestimated the infusion result, assuming the latter to represent the reference method. This might have been due to extrapolation errors in the injection technique, either in the first few minutes following injection, or in the interval after the last sample. However, the notional volumes of distribution of the tracer suggest that the terminal phase of tracer elimination is in fact slightly faster than that predicted on the basis of samples taken during the first 120 min post-injection.

Animals↗

Low-dose phenobarbitone as an indicator of compliance with drug therapy.

1 To assess the potential value of low-dose phenobarbitone (PB) as a marker of compliance we studied the relationship between plasma level of PB and dose (2-16 mg daily) following 3 or 4 weeks treatment in healthy volunteers (n = 26) and in-patient volunteers (n = 7). 2 Also, to simulate poor compliance, PB levels were measured in some volunteers following alternate-day (n = 6) or short-term (n = 5) treatment with similar doses. These levels, expressed as the level: dose ratios (LDRs), did not overlap with those obtained following 3 or 4 weeks of daily PB intake. 3 To evaluate the efficacy of this marker in patients taking other drugs we gave a group of out-patients (n = 24) compound tablets containing B vitamins and a small dose (16 mg) of PB; their compliance over 2-5 weeks was assessed both by measuring plasma levels of PB and residual tablet counting. 4 In the latter study, as well as providing absolute evidence of good compliance by many patients, the plasma levels of PB proved particularly valuable when non-compliant individuals 'forgot' to bring their residual tablets. 5 We suggest that phenobarbitone, in doses low enough to be non-sedative and non-enzyme inducing, is potentially useful as a pharmacological indicator of compliance with drug therapy.

Adult↗

Effect of diazoxide or glucagon on hepatic glucose production rate during extreme neonatal hypoglycaemia.

The relation between hepatic glucose production rate (HGPR) and plasma concentrations of insulin and glucagon was investigated in four term neonates who had severe hypoglycaemia. The hepatic glucose production rate was less than 20% of normal for fasting term neonates in all four babies and yet insulin concentrations were never greater than 12 microU/ml; two babies had very low glucagon concentrations (less than 60 ng/l). Two further neonates with similar histories also had plasma glucagon concentrations that were also extremely low (less than 20 ng/l). A single intravenous bolus of glucagon caused a rapid rise in hepatic glucose production rate towards the normal range, which was sustained for many hours after the bolus had been given. Diazoxide given to one baby suppressed previously 'normal' insulin concentrations still further (4.2 to less than 1.6 microU/ml) and thereby restored the hepatic glucose production rate to normal. In view of the normal plasma insulin concentrations at a time when the hepatic glucose production rate was reduced, we feel that the absolute concentration of insulin may be less important than the insulin/glucagon molar ratio in the control of glucose homeostasis in this group of infants. The changing of this ratio by means of boluses of glucagon may be useful in preventing rebound hypoglycaemia, which so often occurs when dextrose infusions are reduced either accidentally or in an attempt to restart oral feeds.

Blood Glucose↗

Changing pituitary reactivity to follicle-stimulating hormone and luteinizing hormone-releasing hormone after induced ovulatory cycles and after anovulation in patients with polycystic ovarian disease.

Pituitary reactivity to GnRH, characteristic of polycystic ovarian disease (PCOD), has been attributed both to a primary ovarian cause and to hypothalamic-pituitary dysfunction. If the heightened pituitary reactivity characteristic of PCOD patients is secondary to chronic anovulation, ovulatory cycles should produce changes in the LH to FSH ratio and reduce the augmented response to GnRH. In a randomized cross-over study of 10 women with PCOD, GnRH (100 micrograms) was injected iv on the fifth day of 2 consecutive cycles, 1 of them following anovulation and progesterone withdrawal bleeding and the other following an induced ovulatory cycle. Mean basal plasma 17 beta-estradiol, progesterone, and FSH levels were similar after ovulatory and anovulatory cycles. However, mean basal serum testosterone (P less than 0.05) and LH (P less than 0.01) levels were significantly lower, as were LH levels 30, 60, and 90 min (P less than 0.01) and FSH levels 60 and 90 min (P less than 0.05) after GnRH injection, after an ovulatory cycle than after an anovulatory cycle. The pituitary response to GnRH in those PCOD patients, therefore, was more normal after an ovulatory cycle than after an anovulatory cycle. We conclude that the heightened pituitary reactivity characteristic of PCOD patients is associated with chronic anovulation.

Adult↗

The effect of low-dose phenobarbitone on three indices of hepatic microsomal enzyme induction.

The effects of low-dose phenobarbitone on three indices of hepatic enzyme induction were studied. Eight healthy volunteers took phenobarbitone 7.5 mg daily for 4 weeks followed by 15 mg daily for 4 weeks; five subjects took 30 mg daily for a further 2 weeks. Phenobarbitone 15 mg daily produced a significant rise in antipyrine clearance (P less than 0.05). Phenobarbitone 30 mg daily produced a further rise, but probably because of the reduced numbers of subjects, this did not achieve significance (P = 0.06). Urinary 6-beta-hydroxycortisol and D-glucaric acid levels did not change significantly and remained within the range seen in subjects not taking enzyme-inducing drugs. We conclude that phenobarbitone 7.5 mg daily produces little (if any) enzyme induction whereas 15 mg, or more, may have the potential to produce drug interactions through enzyme induction.

Adult↗

Home care ventilation: the Cleveland Clinic experience from 1977 to 1985.

A need for long-term ventilation in the home has created a demand for home care services that has been a source of growth for an industry. Evaluation of the patient and family who will guarantee successful home care requires careful psychological and psychiatric evaluation. Beyond this evaluation, long-term success is possible if appropriate financial resources are available. The implementation of successful home care is best done by a team consisting of primary physician, primary ICU nurse, social worker, psychiatrist, and home care respiratory therapist. An appropriate classification of patients based on goals of care, as well as the study of the incidence and prevalence of associated disorders, will be helpful in the future allocation of resources.

Data Collection↗

Maternal and cord blood glycated albumin and total serum proteins: correlation with maternal glycemic control and birth weight.

Maternal and cord blood glycated albumin and total protein levels were measured in three groups: normal women (nondiabetic women who gave birth to infants that were normal for gestational age), test women (women who had no evidence of glucose intolerance with screening procedures and who gave birth to large for gestational age infants), and women with gestational diabetes. In all cases the cord glycated albumin and total protein levels were 20% to 30% less than the corresponding maternal levels, and no correlation could be detected between cord and maternal blood concentrations. There was no significant difference in cord and maternal glycated albumin and total protein levels among the three groups, although there was a slight upward trend detected in the test and diabetic groups. There was no significant correlation between birth weight ratio and either cord or maternal values for any of the groups except the diabetic cord samples, where a significant negative correlation between glycated albumin and total protein and birth weight ratios was found. The implications of these findings are discussed in respect to the usefulness of cord and maternal glycated albumin and total protein in retrospective screening for gestational diabetes.

Adult↗

Cord blood glycosylated (glycated) hemoglobin: correlation with maternal glycosylated (glycated) hemoglobin and birth weight.

Maternal and cord blood glycosylated hemoglobin levels were measured by an affinity chromatographic method in three groups: normal women (nondiabetic women who gave birth to infants that were normal for gestational age); test women (women who had no evidence of glucose intolerance with screening procedures and who gave birth to large-for-gestational age infants); and women with gestational diabetes. In all cases the level of cord blood glycosylated hemoglobin was approximately 40% less than the corresponding maternal blood levels, and no correlation could be detected between maternal and cord blood concentrations. The reference range for glycosylated hemoglobin in the normal maternal population was similar to that for nonpregnant adults. There was no significant difference in cord and maternal glycosylated hemoglobin levels among the three groups, although a slight upward trend was detected in the diabetic group. There was a lack of correlation of cord and maternal glycosylated hemoglobin with birth weight in all three groups. The implications of these findings are discussed in respect to the usefulness of cord and maternal glycosylated hemoglobin in retrospective screening for gestational diabetes.

Adult↗