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Biomedical subjects

A Sanghvi

Publications and source records attributed to A Sanghvi.

At least 19 recordsLinked to original sources
PubMed2006

When is a door not a door? The difference between documented and actual arrival times in the emergency department.

OBJECTIVES: An observational study to determine the difference between documented ambulance arrival times and the actual arrival times of patients from the ambulance into the emergency department. METHODS: In a busy, purpose built, modern emergency department with easy access, we recorded the time that ambulance borne patients were wheeled over the threshold of the clinical area and compared this to the times recorded by the ambulance trusts as the official ambulance arrival times. RESULTS: 352 ambulance arrivals were observed. Data were incomplete in 34 instances (9.5%) and were not included in the analysis. For the remaining 318 arrivals, the median time difference was 2 min 1 s (range 5 s to 21 min 45 s). In a subgroup of chest pain patients (45 patients), the median time difference was 2 min 11 s (range 23 s to 5 min 38 s). The difference between the chest pain group and the remaining patients was not significant (p = 0.528). CONCLUSIONS: There is inevitably some delay between the arrival of an ambulance and the arrival of the patient into a clinical area. This study quantifies that difference. In an era of stringent time related standards, this paper highlights the need for accurate recording of times to enable us to carry out valid audit of these standards. This study supports the redefining of an arrival time as the time when the patient arrives in the clinical area.

Ambulances↗
PubMed1996

Conjunctival transplantation for corneal surface reconstruction--case reports and review of literature.

Corneal persistent epithelial defects (PED) can occur due to various causes. In diffuse ocular surface disease, they often occur secondary to depletion of limbal stem cells. A number of complications occur secondary to PED and successful treatment usually requires conjunctival surgeries for corneal surface reconstruction. We report two cases of chemical injury successfully treated by two such procedures. This report highlights the encouraging results of limbal transplantation and reviews the literature in the management of PED with limbal stem cell loss.

Adult↗
PubMed1988

Regulation of bile acid synthesis. Isolation and characterization of microsomal phosphatases.

In preliminary experiments, we have shown that rat liver microsomes possess phosphatase activity which was inhibited in the presence of sodium fluoride. We have now separated six microsomal phosphatase fractions appearing to be isoenzymes. They all possess different kinetic constants and are not equally inhibited by tartrate and fluoride ions, inhibitors of phosphatase activity. One phosphatase fraction, in fact, is almost completely unaffected by fluoride ion. More pertinent to our interest, these isoenzymes exhibit differing abilities to modulate the activities of hydroxymethylglutaryl CoA reductase, acyl-CoA:cholesterol O-acetyltransferase, and cholesterol 7 alpha-hydroxylase. Interaction of four of the fractions with rat liver microsomes resulted in a decrease in cholesterol 7 alpha-hydroxylase activity; two were without effect.

Animals↗
PubMed1988

Abbott's fluorescence polarization immunoassay for cyclosporine and metabolites compared with the Sandoz "Sandimmune" RIA.

A new procedure for measuring cyclosporine in plasma has been introduced by Abbott Laboratories, involving their TDx instrumentation and fluorescence polarization immunoassay. Radioimmunoassay (RIA) and high-performance liquid chromatography are currently the conventional methods for measuring cyclosporine in plasma and whole blood. In an effort to find a method that will decrease the radioactive hazard, the reagent and supply cost, and the labor requirements associated with RIA procedures, we used specimens from transplantation patients to compare the Abbott assay with the Sandoz Sandimmune assay. We believe that the Abbott assay offers some advantages over the Sandimmune RIA procedure, providing a reliable but simpler and less hazardous technology.

Cyclosporins↗
PubMed1987

Cyclosporine kinetics in healthy volunteers.

The pharmacokinetics of cyclosporine was studied in five healthy male volunteers following intravenous administration. The subjects received 2.1 mg/kg of cyclosporine as a two-hour intravenous infusion. Blood samples were collected over the subsequent 48 hours. Cyclosporine was extracted from whole blood and analyzed by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Following the intravenous infusion of cyclosporine, the drug exhibited multicompartmental behavior. The harmonic mean distribution half-life based on HPLC data was 0.45 hours, and the harmonic mean terminal disposition half-life was 6.2 hours. The clearance of cyclosporine based on HPLC cyclosporine concentrations was 3.9 mL/min/kg, and the volume of distribution at steady state of cyclosporine was 1.23 L/kg. Cyclosporine has a shorter half-life, lower clearance, and smaller Vss in healthy persons as compared to patient populations. The differences observed in the pharmacokinetics of cyclosporine in healthy persons as compared to patient populations may be due to differences in hematocrit, lipoprotein profiles, and/or concurrent drug therapy between the groups. Cyclosporine concentrations determined by RIA were consistently higher than those determined by HPLC, resulting in a significantly higher area under the blood concentration versus time curve and lower clearance rate for cyclosporine. We conclude that: (1) kinetic parameter estimates for cyclosporine are different in healthy individuals as compared with organ-transplant recipients, and (2) the kinetic parameters for cyclosporine are different, depending on the assay technique used.

Adult↗
PubMed1987

Cyclosporin A-induced cholestasis. The mechanism in a rat model.

Cyclosporin A (CyA) causes cholestasis in a significant proportion of transplant patients. Doses of 5, 10, and 15 mg CyA/kg body wt or the Miglyol 812 vehicle were administered intraperitoneally for 1, 2, and 3 wk to separate groups of rats to investigate the mechanism of this cholestasis. At 1 wk a dose-response relationship between serum CyA levels and increasing CyA doses was noted. A maximum CyA blood level was achieved by 2 wk with the 10- and 15-mg/kg doses. Subsequent studies were performed using the smaller (10 mg/kg) dose administered for 3 wk. This dose resulted in a marked increase in serum bile acid levels compared with vehicle-treated controls (24.6 +/- 4.0 vs. 4.3 +/- 1.2 mumol/L, p less than 0.001) without inducing significant changes in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, bilirubin, alkaline phosphatase, and albumin levels or hepatic architectural alterations. With CyA treatment, baseline bile flow decreased by 35% and bile salt secretion decreased by 25% compared with vehicle-treated animals. Cyclosporin A and vehicle-treated rats were infused intravenously with taurocholate (4 mumol/min X kg) for 2 h and then depleted of bile salts over the next 24 h. Bile samples collected over this period were graphed as bile salt secretion versus bile flow. The mean slope of the linear regression for the CyA-treated rats was 62% of the control, demonstrating a decrease in bile salt-dependent flow. Extrapolation of the linear regression to the ordinate demonstrated a 22% decrease in bile-independent flow with CyA treatment. Therefore, in our experimental model of CyA-induced cholestasis, the decrease in flow observed was the result of a decrease in both bile salt-dependent and bile salt-independent flows and occurred in the absence of significant biochemical or histologically evident hepatotoxicity.

Animals↗
PubMed1986

Effect of insulin on low-density-lipoprotein metabolism in human lymphocytes in vitro.

The metabolism of low-density lipoproteins (LDL) in vitro in the presence of insulin was studied in freshly isolated human peripheral-blood lymphocytes. Insulin appeared to decrease the binding affinity of 125I-LDL to its cell-surface receptor, without any change in apparent Vmax or in the number of LDL receptors. As a consequence, the absolute amounts of 125I-LDL internalized and degraded were lower in the presence of insulin than in its abscence, although the fraction of internalized 125I-LDL degraded in either instance was quite similar. 3-Hydroxy-3-methylglutaryl-CoA reductase activity, and hence cholesterol synthesis, were stimulated by insulin. This effect of insulin was independent of the inhibitory effect of LDL on cholesterol synthesis. At the same time, acid cholesterol esterase and acyl-CoA: cholesterol O-acetyltransferase activities were lower in cells incubated with insulin than in controls. The net effect of these metabolic alterations seems to be that cells accumulate greater quantities of free and esterified cholesterol when treated with insulin.

AMP-Activated Protein Kinases↗
PubMed1986

Thyroid and pituitary hormone responses to TRH in advanced nonalcoholic liver disease.

Basal T4, T3, TSH, prolactin and growth hormone levels were determined in several groups: patients with postnecrotic cirrhosis with hepatocellular carcinoma (n = 14); patients with postnecrotic cirrhosis but without hepatocellular carcinoma (n = 26); cholangiolar carcinoma (n = 9); and normal controls age-matched to within 5 yr of the liver disease subjects studied. In addition, TRH stimulation (400 micrograms TRH) was performed; TSH, prolactin and growth hormone responses over a 180-min time interval were evaluated for each subject. The responses observed varied between liver disease groups. The presence or absence of hepatocellular carcinoma was found to determine, at least in part, the type of response observed. Similarly, the presence or absence of hepatic encephalopathy determined, and/or reflected, at least in part, the type of response observed. Finally, for purposes of continuity, basal and TRH-stimulated levels of TSH, prolactin, growth hormone, T4 and T3 are compared in 3 settings of cirrhosis: alcoholic, nonalcoholic postnecrotic cirrhosis, and postnecrotic cirrhosis with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1986

Cyclosporine metabolism and pharmacokinetics following intravenous and oral administration in the dog.

The influence of assay method on single dose cyclosporine (CsA) pharmacokinetics was studied in nine dogs receiving either i.v. or oral CsA. Samples were drawn from hepatic, portal, and systemic veins at various times after the dose and CsA levels were determined by radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC). Blood concentration-time data were analyzed by nonlinear least-squares regression, using two-compartment models. RIA/HPLC ratios for all samples were greater than one, and did not change significantly over time. The mean RIA/HPLC ratios for samples drawn from all three veins were higher after oral than i.v. doses of the drug (P less than 0.05). Area under the concentration-time curve (AUC) was higher and systemic clearance (CIs) lower than calculated on the basis of RIA results, regardless of the route of administration. AUC calculated for CsA metabolites (RIA-HPLC) was highest in the portal vein after an oral dose of CsA. Bioavailability was 20.4% and 27.0% when estimated using HPLC and RIA data, respectively. The mean CsA metabolite index (CMI), when calculated for hepatic, portal, or systemic vein, was greater when the drug was administered orally. The mean hepatic extraction ratio (HER) of the parent drug and for CsA metabolites was approximately 23% in i.v. and p.o. studies. These results suggest that the gastrointestinal tract may play a role in the metabolism of CsA when the drug is administered orally. In addition, if CsA metabolites not measured by HPLC have either toxic or immunosuppressive properties, the RIA assay may be more useful for monitoring patients.

Administration, Oral↗
PubMed1986

Impact of organ transplant program on the Clinical Chemistry Laboratory at the University of Pittsburgh.

The success of cyclosporine in immunosuppressive therapy in organ transplantation suggests that such existing programs may expand in scope, and new programs may be initiated at institutions that currently do not have them. Significant clinical laboratory support and the allocation of laboratory resources are necessary to sustain an organ transplant program. At the University of Pittsburgh, the number of transplant-related clinical chemistry procedures (primarily cyclosporine and liver and renal function tests) increased from 1.4% of the total chemistry tests in 1979-1980 to 21% of the total in 1983-1984. There was a concomitant increase in cost for transplant chemistry tests as follows: $47,000 in the fiscal year 1979-1980 to $1,250,000 in the fiscal year 1983-1984. Measurement of blood cyclosporine levels alone can consume a large fraction of a total laboratory budget; from being a negligible expense at the end of March 1983, it escalated to almost $300,000 by October 1984. Our experience in this regard indicates that it is difficult to gauge the magnitude of necessary laboratory resource commitment to such a program a priori with any degree of certainty. In this context, the capacity to be flexible in assigning laboratory resources appears critical.

Chemistry, Clinical↗
PubMed1985

Regulation of bile-acid synthesis. Role of sterol carrier protein 2 in the biosynthesis of 7 alpha-hydroxycholesterol.

Sterol carrier protein2 (SCP2) is known to stimulate utilization of cholesterol in enzymic reactions in which cholesterol is the substrate. Substantial recent experimental evidence indicates that SCP2: activates enzymic conversion of intermediates between lanosterol and cholesterol; stimulates the microsomal conversion of cholesterol into cholesterol ester in rat liver; and enhances mitochondrial utilization of cholesterol for pregnenolone formation in the adrenals. The conversion of cholesterol into 7 alpha-hydroxycholesterol is the rate-limiting step in bile-acid synthesis. We therefore investigated the effect of SCP2 on this physiologically critical reaction by using a gas-chromatography-mass-spectrometry procedure that measures the mass of 7 alpha-hydroxycholesterol formed. The results show that SCP2 enhances 7 alpha-hydroxycholesterol formation by rat liver microsomes (microsomal fractions), utilizing either endogenous membrane cholesterol, cholesterol supplied exogenously in serum or in the form of cholesterol/phospholipid liposomes. Microsomes immunotitrated with anti-SCP2 antibody exhibited considerably less capacity to synthesize 7 alpha-hydroxycholesterol, which was restored to control levels on addition of purified SCP2. These data are consistent with the suggestion that SCP2 may be of physiological significance in the overall metabolism of cholesterol.

Animals↗