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Biomedical subjects

M W Stewart

Publications and source records attributed to M W Stewart.

At least 37 records · Page 2Linked to original sources
PubMed1997

Platelet activation by a novel solid-phase agonist: effects of VWF immobilized on polystyrene beads.

The interaction between platelets stirred in suspension and VWF immobilized on polystyrene beads was studied. Platelets aggregated and released ATP in response to stirring with VWF beads. Closer examination of the interaction using transmission electron microscopy revealed that the platelets did not simply aggregate with one another but initially adhered to the beads and spread. Platelets in suspension then bound to the bead-adherent platelets forming layers of platelets associated with each bead. The VWF bead-induced platelet activation was completely inhibited by addition of monoclonal antibody (mAb) to GPIb or GPIIb/IIIa. In addition, the activation response was inhibited in the presence of aspirin, indomethacin or the thromboxane receptor antagonist BM13.177, demonstrating a dependence on an intact cyclo-oxygenase pathway. Platelet function studies were carried out on 30 patients with a history of mild bleeding using conventional optical aggregation and VWF bead-induced platelet activation. 12 patients were abnormal by conventional optical aggregometry, whereas 27 patients showed depressed ATP release in response to VWF beads. The results suggest that easily-bruised patients may have a platelet function defect rather than a vascular-based abnormality and that VWF bead-induced platelet activation is a more sensitive test for detecting platelet dysfunction.

Aspirin↗
PubMed1997

Antiphospholipid antibody-dependent C5b-9 formation.

The relationship between the presence of antiphospholipid antibodies (APA) and the production of the terminal membrane attack complex (MAC) of complement (C5b-9) was studied. Serum samples from known high positive APA patients induced platelet activation and destruction which was inhibited by heat-inactivation of the sera. The response was restored if the heat-inactivated APA-positive sera were supplemented with normal sera. Adsorption of the APA-positive sera with phospholipid (PL)-coated polystyrene beads inhibited platelet destruction. Addition of monoclonal antibody (mAb) to C5b-9 (aE11) also inhibited platelet destruction, suggesting that the APA-dependent platelet destruction might be complement-mediated. Purified APA, in the presence of normal serum, induced C5b-9 formation and binding to PL-coated beads in a dose-dependent manner as detected by flow cytometry. Prospective analysis of 200 serum samples for C5b-9 production showed that all sera testing negative for the presence of APA also tested negative for C5b-9 production. All sera with high levels of IgG binding to PL (GPL) showed evidence of C5b-9 production. Sera with low or moderate GPL values showed varying levels of C5b-9 production. These data suggest that complement may play a key role in APA-dependent platelet activation, in vivo.

Adenosine Triphosphate↗
PubMed1997

National health expenditures, 1996.

The national health expenditures (NHE) series presented in this report for 1960-96 provides a view of the economic history of health care in the United States through spending for health care services and the sources financing that care. In 1996 NHE topped $1 trillion. At the same time, spending grew at the slowest rate, 4.4 percent, ever recorded in the current series. For the first time, this article presents estimates of Medicare managed care payments by type of service, as well as nursing home and home health spending in hospital-based facilities.

Drug Prescriptions↗
PubMed1996

Human insulin receptor substrate-1: variant sequences in familial non-insulin-dependent diabetes mellitus.

The aetiology of NIDDM is uncertain, although family and twin studies indicate an important role for genetic factors in disease onset. The function and position of IRS-1 within the insulin signalling pathway make it a prime candidate gene for the development of insulin resistance and NIDDM. Insulin resistant families were identified by studying unaffected first degree relatives from families with 2 or more living NIDDM subjects. Insulin sensitivity was determined in the relatives using the insulin tolerance test, and 15 families were identified as insulin resistant. One NIDDM subject from the 10 most resistant families was selected and the entire coding region of IRS-1 analysed by SSCP analysis. Four normoglycaemic subjects with no family history of diabetes served as controls. Five variant sequences of IRS-1 were identified with the NIDDM subjects; 2 silent polymorphisms at codons 235 (GGG to GGA) and 893 (CCG to CCC): 2 non-conservative mutations (Ala513Pro; Gly972Arg) and a codon deletion (Ser681-7 to Ser681-6). The influence of the non-conservative mutations alone, and in combination with other abnormalities of the insulin signalling pathway on peripheral insulin action, remains to be determined.

Base Sequence↗
PubMed1996

Relationship between insulin sensitivity and insulin receptor substrate-1 mutations in non-diabetic relatives of NIDDM families.

Insulin receptor substrate-1 (IRS-1) occupies a key position in the insulin-signalling pathway. Two mutations of the IRS-1 gene (Gly(972)Arg and Ala(513)Pro) have been described, although their roles in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) remain controversial. Insulin resistance has been described in non-diabetic relatives of NIDDM families, suggesting that it may be due to an inherited defect of insulin action. We therefore examined the relationships between the two mutations and insulin sensitivity in 93 non-diabetic first degree relatives from North European families with 2 or more living NIDDM subjects. Anthropometric measurements, an oral glucose tolerance test, and an insulin tolerance test to assess insulin sensitivity (K(ITT)) were performed. Basal insulin sensitivity was assessed by homeostasis model assessment (HOMA). Comparisons were made between the following relative subgroups: with (n = 9) and without (n = 84) the 972 mutation; with (n = 5) and without (n = 88) the 513 mutation; and with either one or both mutations (n = 13) or without either (n = 80). General linear model analysis was used to compare K(ITT) and HOMA between the subgroups with the anthropometric variables known to influence insulin sensitivity as covariates. There were no significant differences between the subgroups for K(ITT) and HOMA. In conclusion, the 513 and 972 mutations, alone and in combination, are not associated with decreased insulin sensitivity in non-diabetic relatives of NIDDM families.

Adult↗
PubMed1996

Self-monitoring of triglycerides by type 2 diabetic patients: variability in fasting and postprandial levels.

Triglycerides are an important risk factor for coronary heart disease in Type 2 (non-insulin-dependent) diabetes mellitus. Although Type 2 diabetic patients have an exaggerated postprandial triglyceride response to a fat meal test, little is known about the variability of triglyceride concentrations in day-to-day life. We have studied the variability in triglyceride concentrations in 24 Type 2 diabetic patients over 6 months by having them record fasting and postprandial triglyceride concentrations at home using a Reflotron dry chemistry analyser. All patients were able to use the analyser effectively, with a correlation of 0.97 between patients' monthly Reflotron readings and those recorded by the laboratory. Over 1600 measurements were performed. The results demonstrate a large variation in both fasting (median 1.95 mmol l-1, range 0.8-6.7 mmol l-1) and postprandial triglyceride concentrations (median 2.68 mmol l-1, range 0.8-6.7 mmol l-1). This variation was accounted for by both a large intra- and inter-individual variation. Although there was a strong correlation overall between fasting and postprandial triglyceride concentrations r = 0.925 (p < 0.001), this did not apply on an individual basis. In conclusion, the large variability in triglyceride concentrations should be considered before introducing pharmacological therapy for hypertriglyceridaemia in Type 2 diabetes mellitus.

Body Mass Index↗
PubMed1996

Lipoprotein (a) concentrations and apolipoprotein (a) phenotypes in normoglycaemic relatives of type 2 diabetic patients.

Serum lipoprotein (a) concentrations (Lp(a)) are largely under genetic control, and are strong predictors of coronary heart disease. It has been hypothesised that Lp(a) may contribute to the increased risk of coronary heart disease in familial Type 2 diabetes mellitus. We therefore examined the Lp(a) concentrations and the apolipoprotein (a) (apo(a)) phenotypes in 126 normoglycaemic first degree relatives from families with two or more living Type 2 diabetic patients. These were compared with 147 sex matched normoglycaemic control subjects with no family history of diabetes. Lp(a) concentrations were measured using an enzyme-linked immunosorbent assay (ELISA), and apo(a) isoforms were determined and classified according to the relative mobility of apo(a) on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), relative to that of apolipoprotein B-100. There were no significant differences in Lp(a) concentrations between the relatives (R) and controls (C): 11.2 (R) vs. 11.1 (C) mg/dl (median). The distribution of apo(a) phenotypes was not significantly different between groups 0.65 (R) vs. 0.67 (C). These results show that first degree relatives at risk of developing Type 2 diabetes do not have abnormal Lp(a) concentrations or apo(a) phenotypes.

Adult↗
PubMed1996

Bleeding in a patient taking Lorenzo's oil: evidence for a vascular defect.

We describe a man with adrenoleukodystrophy receiving Lorenzo's oil (glycerol trioleate and glycerol trierucate) who developed purpura, petechiae, and bleeding. Bleeding time was markedly increased (>20 min), although he had only borderline thrombocytopenia (120 x 10(9)/1) and conventional platelet aggregation studies were normal (except for a borderline response to low concentration collagen), as were results using a new technique employing immobilised von Willebrand factor. Together these results suggest that bleeding in this man resulted from a defect in vascular wall function or in the interaction of platelets with the endothelium.

Adrenoleukodystrophy↗
PubMed1996

National health expenditures, 1994.

This article presents data on health care spending for the United States, covering expenditures for various types of medical services and products and their sources of funding from 1960 to 1994. Although these statistics for 1994 show the slowest growth in more than three decades, health spending continued to grow faster than the overall economy. The Federal Government continued to fund an increasing share of health care expenditures in 1994, offset by a falling share from out-of-pocket sources. Shares paid by State and local governments and by other private payers including private health insurance remained unchanged from 1993.

Ambulatory Care↗
PubMed1996

National health expenditures, 1995.

This article presents data on health care spending for the United States, covering expenditures for various types of medical services and products and their sources of funding from 1960 to 1995. In 1995, $988.5 billion was spent to purchase health care in the United States, up 5.5 percent from 1994. Growth in spending between 1993 and 1995 was the slowest in more than three decades, primarily because of slow growth in private health insurance and out-of-pocket spending. As a result, the share of health spending funded by private sources fell, reflecting the influence of increased enrollment in managed care plans.

Advertising↗
PubMed1995

Binding of cardiolipin to polystyrene beads: evidence for a lamellar phase orientation.

The association of cardiolipin with polystyrene beads was studied using 31P-NMR and electron microscopy. In the presence and absence of fetal calf serum, cardiolipin appeared to bind to the polystyrene beads in lamellar phase as assessed by 31P-NMR imaging. Electron microscopic analysis revealed an even coating of phospholipid about the beads with extensive micelle binding. Cardiolipin-coated beads challenged with ACA-positive sera followed by immunogold indicated antibody bound to micelles associated with the bead. Studies conducted with ACA IgG purified from patient sera indicated that some ACA bound to CL beads in the absence of a source of ACA cofactor (i.e. gelatin-blocked beads), some ACA required beta 2-GPI for binding (i.e. no binding in the presence of beta 2-GPI-depleted plasma), whereas other ACA which showed negligible binding with gelatin-blocked beads, showed enhanced binding in the presence of beta 2-GPI-depleted plasma. The data indicate that: (1) cardiolipin binds to polystyrene beads in lamellar phase, (2) ACA bind to phospholipid micelles bound directly to the polystyrene beads, and (3) ACA differ between individuals displaying varying phospholipid and phospholipid/cofactor substrate specificities.

Antibodies, Anticardiolipin↗
PubMed1995

Heparin-induced thrombocytopenia: an improved method of detection based on lumi-aggregometry.

Heparin-induced thrombocytopenia (HIT) is a recognized complication of heparin administration. Early detection of this syndrome is essential in the prevention of immune-mediated thromboembolic sequelae. The 14C-serotonin release assay (SRA) has been used in reference laboratories to identify sera from patients on heparin therapy capable of inducing platelet dense granule release. In an attempt to improve existing methodologies, we employed luminographic detection of platelet-dense granule ATP release as an endpoint of HIT antibody-mediated platelet activation. Sera tested included 10 SRA confirmed positive and five SRA confirmed negative samples (to establish the assay), five samples from patients with thrombocytopenia not on heparin therapy and 34 patients suspected of HIT syndrome. All SRA confirmed positive sera (n = 19) were positive by the luminographic procedure. 24/26 SRA confirmed negative sera and five sera from thrombocytopenic patients not on heparin therapy were negative using luminography. Two of four sera yielding equivocal SRA results were found to be positive by the luminographic technique. The data suggest that the use of a lumiaggregometer in the coagulation laboratory to detect HIT antibody-induced platelet activation is a reliable alternative to the SRA. The luminographic procedure is both rapid and sensitive, and does not require the use of biohazardous radio-isotopes.

Adenosine Triphosphate↗
PubMed1995

The effects of lipid lowering drugs on metabolic control and lipoprotein composition in type 2 diabetic patients with mild hyperlipidaemia.

Patients with Type 2 diabetes are at increased risk from macrovascular disease whether or not they are hyperlipidaemic. Several factors may contribute to this increased risk including abnormalities of lipoprotein composition. The aim of our study was to determine the effects of lipid lowering drugs on lipoprotein composition (lipoprotein fractions were separated by sequential flotation ultracentrifugation) and insulin sensitivity (measured by a modified Harano technique) in 44 patients with mild hyperlipidaemia. All patients had total cholesterol concentrations between 5.2 and 6.5 mmol l-1 and total triglyceride concentrations < 3.0 mmol l-1, and were randomized by minimization to receive treatment for 12 weeks with bezafibrate, acipimox, simvastatin or placebo. Total cholesterol concentrations were decreased by simvastatin, 5.7 +/- 0.4 to 3.7 +/- 0.6 mmol l-1 (p < 0.05), due mainly to reduced LDL-cholesterol levels (-1.25 mmol l-1; p < 0.05), and bezafibrate 5.7 +/- 0.6 to 4.6 +/- 0.4 mmol l-1 (p < 0.05). The LDL:HDL-cholesterol ratio was reduced in the simvastatin group 2.0 +/- 0.5 to 1.2 +/- 0.3 (p < 0.005). There was no effect of the drugs on glycated haemoglobin or insulin sensitivity. In conclusion bezafibrate and simvastatin improve the lipid profile in Type 2 diabetic patients without adversely affecting diabetic control.

Apolipoproteins B↗
PubMed1995

Features of syndrome X in first-degree relatives of NIDDM patients.

OBJECTIVE: To determine whether the features of syndrome X are more common in first-degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients than in control subjects with no family history of diabetes. RESEARCH DESIGN AND METHODS: A total of 154 first-degree relatives from 60 families with two or more NIDDM patients and 154 age- and sex-matched control subjects were studied. All subjects underwent a 75-g oral glucose tolerance test and baseline lipid blood and anthropometric measures. The features of syndrome X that were studied were obesity, hypertension, dyslipidemia (high triglyceride levels and low high-density lipoprotein [HDL] cholesterol concentrations), impaired glucose tolerance (World Health Organization criteria), and insulin resistance (as assessed by the homeostasis model assessment). RESULTS: Relatives were heavier than control subjects (body mass index 27.5 +/- 5.2 vs. 25.2 +/- 4.6 kg/m2, respectively [mean +/- SD], P < 0.0002), had lower HDL cholesterol concentrations (1.2 +/- 0.3 vs. 1.4 +/- 0.4 mmol/l, P < 0.001), were more insulin-resistant (2.3 [0.7-7.6] vs. 1.6 [0.5-5.1], geometric mean [95% confidence intervals], P < 0.0001), and had more individuals classified as having impaired glucose tolerance (28 of 154 [18%] vs. 7 of 154 [7%], chi 2, P < 0.001). The differences in insulin resistance and HDL cholesterol concentrations between the groups were independent of obesity. CONCLUSIONS: Features of syndrome X occur more frequently in relatives of NIDDM patients than in control subjects with no family history of diabetes.

Adult↗
PubMed1995

Justifying the cost of a computer-based patient record.

Computer-based patient records (CPRs) that integrate financial and clinical information are important tools for improving the quality and lowering the cost of care. However, purchasing, implementing, and maintaining a CPR requires a significant investment that must be justified. At The University of Texas M. D. Anderson Cancer Center, a cost-benefit analysis of a CPR involved identifying the goals of a CPR, determining its quantifiable and nonquantifiable benefits, estimating its initial costs, projecting its costs and benefits over 10 years, calculating its net present value, and monitoring its results.

Cancer Care Facilities↗