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Biomedical subjects

S Clark

Publications and source records attributed to S Clark.

At least 145 records · Page 8Linked to original sources
PubMed1997

Differential disposition of lysophosphatidylcholine in diabetes compared with raised glucose: implications for prostaglandin production in the diabetic kidney glomerulus in vivo.

An early increased formation of renal prostaglandins in diabetes which follows the hydrolysis of cellular phospholipids by cytosolic phospholipase A2 is of considerable importance in determining subsequent cellular function. As the disposition of concomitantly formed lysophosphatidylcholine may also affect cellular function, we investigated the cellular fate of exogenous lysophosphatidylcholine in mesangial cell-enriched glomerular cores and showed that in cells taken from diabetic rats there is an increased net reformation of phosphatidylcholine. Positional distribution of labelled palmitate from sn-1 position palmitate-labelled lysophosphatidylcholine showed distribution to both sn-1 and sn-2 position of the phosphatidylcholine formed with a significantly increased sn-2 position labelling in diabetes. Although both a coenzyme A-dependent acyltransferase activity and a coenzyme A-independent transacylase activity could be shown in these cells, the increased phosphatidylcholine formation in cells taken from diabetic animals was due to an increase in coenzyme A-independent transacylase activity. By contrast, an increase in coenzyme-A independent transacylase activity could not be demonstrated in cultured mesangial cells maintained with prolonged raised glucose concentrations. Cell homogenates possess the ability to transfer fatty acid from lysophosphatidylcholine to lysophosphatidylcholine and lysophosphatidylethanolamine with subsequent formation of phosphatidylcholine and phosphatidylethanolamine, respectively. In preparations from diabetic animals phosphatidylethanolamine formed in this manner was increased in the presence of an inhibitor of cytosolic phospholipase A2, indicating that it may provide a substrate for phospholipase A2 activity; an effect not seen in cultured cells maintained at raised glucose concentrations. It is concluded that one effect of an altered disposition of lysophosphatidylcholine in cells from diabetic animals would be to spare fatty acids released following phospholipase A2 hydrolysis of phospholipid, possibly providing the substrate for prostaglandin production, an effect not seen with raised glucose alone.

Acyltransferases↗
PubMed1997

Nutritional management of cardiovascular risk factors. A randomized clinical trial.

BACKGROUND: Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction. OBJECTIVE: To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan. METHODS: This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the Harris-Benedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks. MAIN OUTCOME MEASURES: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life. RESULTS: Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P < or = .001 for all findings except low-density lipoprotein-high-density lipoprotein ratio, P = .25) all improved on both nutrition plans. Mean differences (+/-SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-group P values), respectively, were as follows: systolic BP, -6.4 +/- 9.2 mm Hg and -4.6 +/- 9.0 mm Hg (P = .02); diastolic BP, -4.2 +/- 5.7 mm Hg and -3.0 +/- 5.1 mm Hg (P = .006); cholesterol, -0.32 +/- 0.58 mmol/L and -0.27 +/- 0.56 mmol/L (-12.4 +/- 22.5 mg/dL and -10.4 +/- 21.9 mg/dL) (P = .30); glucose, -0.65 +/- 1.88 mmol/L and -0.75 +/- 2.03 mmol/L (-11.7 +/- 34.0 mg/dL and -13.5 +/- 36.6 mg/dL) (P = .10); and HbA1c, -0.4% +/- 0.8% and -0.3% +/- 0.7% (P = .66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5 +/- 3.6 kg and -3.5 +/- 3.3 kg; and women, -4.8 +/- 3.0 kg and -2.8 +/- 2.8 kg. Quality of life was significantly improved for daily and work activities (P < .05) and nutritional health perceptions (P < .05) with the CCNW plan relative to the self-selected group. Overall nutrient intake and compliance were both significantly (P < .001) better with the CCNW plan. CONCLUSIONS: Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease.

Adult↗
PubMed1997

Engineered cell lines for insulin replacement in diabetes: current status and future prospects.

The recently completed diabetes complications and control trial has highlighted the need for improvement of insulin delivery systems for treatment of insulin-dependent diabetes mellitus. Despite steady improvement in methods for islet and whole pancreas transplantation over the past three decades, the broad-scale applicability of these approaches remains uncertain due in part to the difficulty and expense associated with procurement of functional tissue. To address this concern, we and others have been using the tools of molecular biology to develop cell lines with regulated insulin secretion that might serve as a surrogate for primary islets or pancreas tissue in transplantation therapy. This article seeks to provide a brief summary of the current status of this growing field, with a particular emphasis on progress in producing cell lines with appropriate glucose-stimulated insulin secretion.

Cell Line↗
PubMed1997

Generalizability of the limits of stability test in the evaluation of dynamic balance among older adults.

OBJECTIVE: Reliability of platform posturography tests is essential for the identification and treatment of balance-related disorders. The purposes of this study were to establish the reliability of the limits of stability (LOS) test and to determine the relative variance contributions from identified sources of measurement error. DESIGN: Generalizability theory was used to calculate (1) variance estimates and percentage of variation for the sources of measurement error, and (2) generalizability coefficients. Random effects repeated measures analysis of variance (RM ANOVA) was used to assess consistency of measurements across both days and targets. PARTICIPANTS: Thirty-eight community-dwelling older adults with no recent history of falls. MAIN OUTCOME MEASURES: Outcome measures derived from the LOS tests included movement velocity (MV), maximum center of gravity (COG) excursion (ME), end point COG excursion (EE), and directional control (DC). RESULTS: Estimated generalizability coefficients for 2 and 3 days of testing ranged from .69 to .91. Relative contributions of the day facet were minimal. The RM ANOVA results indicated that for three of the movement variables, no significant differences in scores were observed across days. CONCLUSIONS: The 75% and 100% LOS tests are reliable tests of dynamic balance when administered to healthy older adults with no recent history of falls. Dynamic balance measures were generally consistent across multiple evaluations.

Aged↗
PubMed1997

Pruritus in chronic hepatitis C: association with high serum bile acids, advanced pathology, and bile duct abnormalities.

Pruritus is a common symptom of chronic cholestatic liver diseases but is considered rare in chronic hepatitis. We observed pruritus to be an unusually common complaint in patients with advanced chronic hepatitis C. We reviewed the records of 175 chronic hepatitis C patients to identify patients with severe, diffuse, unexplained pruritus; 12 consecutive prospective patients undergoing liver biopsy for chronic hepatitis C served as controls. Assessment included laboratory biochemical tests and assessment of liver pathology by stage, grade, hepatic activity index, and a bile duct score. Pruritus was present in nine (5.1%) patients. Serum AST, ALT, alkaline phosphatase, GGTP, total bilirubin, and ferritin were similar in pruritics and controls. Pruritics had higher serum bile acids (2028.4 +/- 223.1 mmol/liter vs 423.1 +/- 194.3, P < 0.001), higher transferrin saturation (57.5 +/- 6.8% vs 33.2 +/- 3.3, P < 0.01), and lower HCV RNA by bDNA (24.5 +/- 12.7 x 10(5) vs 172.7 +/- 54.1 x 10(5), P < 0.05). Pathology revealed cirrhosis in 6/9 (66.6%) pruritics vs 1/12 (8.3%) controls (P < 0.01). Pruritics had higher pathologic stage (3.7 +/- 0.2 vs 2.2 +/- 0.4, P < 0.01), grade (4.4 +/- 0.2 vs 2.1 +/- 0.2, P < 0.001), activity index (14.3 +/- 1.9 vs 8.6 +/- 1.9, P < 0.025), and bile duct score (7.6 +/- 0.6 vs 4.7 +/- 0.4, P < 0.01). Of eight pruritics treated with IFN-alpha2b, two had complete ALT response and one relapsed. Pruritus followed a relapsing course and only three patients partially responded despite a variety of interventions. In conclusion, pruritus is a common complication of advanced CHC. Its presence is associated with high serum bile acids, advanced pathology and bile duct abnormalities. The clinical course of pruritus is relapsing and response to therapy is inconsistent. These features suggest that pruritus in CHC has a pathogenesis that may vary from that of chronic cholestatic diseases.

Antiviral Agents↗
PubMed1997

Diagnosis of perinatal human immunodeficiency virus infection by polymerase chain reaction and p24 antigen detection after immune complex dissociation in an urban community hospital.

Results of polymerase chain reaction (PCR) and p24 antigen detection after immune complex dissociation (p24-ICD) were compared with antibody results after 18 months of age for human immunodeficiency virus (HIV) diagnosis in 345 prospectively followed, perinatally exposed infants. Of 59 infected and 286 uninfected infants tested at 1-6 months of age, sensitivity and specificity were, respectively, 100% and > 97% for PCR and 90% and > 97% for p24-ICD. Testing was done on > or = 2 occasions in the first 6 months of life in 43 infected infants; 77% had > or = 2 positive results with the same test. Of these infants, 68% had 2 positive p24-ICD tests. In uninfected infants, 96% had only negative tests; none had > 1 positive. By 6 months, all uninfected infants with > or = 2 PCR results could have been diagnosed. HIV status can be determined by PCR by age 6 months in most HIV-exposed infants. p24-ICD should not be used alone, because of its lower sensitivity, but may be useful in areas without advanced laboratory support.

Antigen-Antibody Complex↗
PubMed1997

Dietary compliance and cardiovascular risk reduction with a prepared meal plan compared with a self-selected diet.

Noncompliance with therapeutic diets remains a major obstacle to achieving improvements in cardiovascular disease (CVD) morbidity and mortality. This study compared dietary compliance and CVD risk factor response to two dietary interventions designed to treat hypertension, dyslipidemia, and diabetes mellitus. In a multicenter trial, 560 adults were randomly assigned to either a self-selected, mixed-food plan (n = 277), or a nutrient-fortified prepared meal plan (n = 283); each was designed to provide 15-20% of energy from fat, 55-60% from carbohydrate, and 15-20% from protein. Nutrient intake was estimated from 3-d food records collected biweekly throughout the 10-wk intervention. Compliance was determined by evaluating the participants' ability to meet specific criteria for energy intake [+/-420 kJ (100 kcal) from the midpoint of the prescribed energy range], fat intake (< 20%, < 25%, or < 30% of energy from total fat), and the National Cholesterol Education Program/American Heart Association Step 1 and 2 diet recommendations. Compliance with energy, fat, and Step 1 and 2 criteria was better in participants who followed the prepared meal plan than in those who followed the self-selected diet (P < 0.0001). Compliant participants in both groups achieved greater reductions in body weight, systolic and diastolic blood pressure, and total and low-density-lipoprotein cholesterol than noncompliant participants (P < 0.05). In general, better endpoint responses were observed with lower fat intakes regardless of group assignment. The prepared meal plan is a simple and effective strategy for meeting the many nutrient recommendations for CVD risk reduction and improving dietary compliance and CVD endpoints.

Adult↗
PubMed1997

Cumulative pregnancy rates in couples with anovulatory infertility compared with unexplained infertility in an ovulation induction programme.

Using a retrospective analysis, we compared cumulative pregnancy rates, early pregnancy failure rates and multiple pregnancy rates in couples with polycystic ovarian syndrome (PCOS) (n = 148), hypogonadotrophic or eugonadotrophic hypogonadism (n = 91) and unexplained infertility (n = 117), who were treated in an ovulation induction clinic between January 1991 and December 1995. The women were treated with either human menopausal gonadotrophin (HMG) or purified follicle stimulating hormone (FSH). The cumulative pregnancy rate (derived from life-table analysis) after four ovulatory treatment cycles was 70% in the PCOS group, 74% in the hypogonadism group and 38% in the unexplained infertility group. The cumulative pregnancy rate in the unexplained infertility group was significantly lower than the other groups (P < 0.001) but there was no significant difference between PCOS and hypogonadism using the log rank test. The early pregnancy failure rate was 25% in the PCOS group, 27% in the hypogonadism group and 26% in the unexplained infertility group (chi(2) = 0.132, not significant). The multiple pregnancy rate was 20% in the PCOS group, 30% in the hypogonadism group and 17% in the unexplained infertility group (chi(2) = 2.105, not significant). Treatment of anovulatory infertility using HMG or FSH is effective irrespective of the cause. Couples with unexplained infertility are less successfully treated using HMG: correction of unexplained infertility may involve more than simple correction of possible subtle ovulatory defects.

Adult↗
PubMed1997

Language background, English language proficiency and medical communication skills of medical students.

Associations between language background, English language proficiency and medical communication skills were investigated in a group of 149 third year undergraduate medical students studying at an Australian university. Written and aural English proficiency were assessed with the Screening Test for Adolescent Language (STAL). Medical communication skills and the fluency of spoken language were scored during an Observed Structured Clinical Interview (OSCI), rated by a standardized patient and a clinician. An association was found between language background, performance on the STAL and spoken language proficiency. Satisfactory performance in medical communication skills was not associated with language background or overall performance on the STAL. In this study it was the global rating of unsatisfactory spoken language fluency that was associated with poorer performance in medical communication skills under examination conditions.

Adult↗
PubMed1997

The feasibility of establishing an Australian College of Rural and Remote Health.

The establishment of an Australian College of Rural and Remote Health was recommended at the Third National Rural Health Conference and subsequently endorsed by the National Rural Health Alliance. This paper outlines the progress of a feasibility study, conducted by the National Association of Rural Health Training Units, to determine the prospective role and level of support for the establishment of such a college among health professional groups in Australia. The findings of two national workshops indicated strong support for 'an organizational structure' to facilitate the development of national standards for rural and remote health education and training. While the exact nature of an organizational structure is yet to be determined, it was clear from the workshops that the formation of a college is not feasible at this time. The paper recommends an alternative collaborative forum: an Australian Consortium of Rural and Remote Health.

Attitude of Health Personnel↗
PubMed1997

Leptin inhibits insulin binding in isolated rat adipocytes.

Leptin is secreted from adipose tissue, and is thought to act as a 'lipostat', signalling the body fat levels to the hypothalamus resulting in adjustments to food intake and energy expenditure to maintain body weight homeostasis. In addition, plasma leptin concentrations have been shown to be related to insulin sensitivity independent of body fat content, suggesting that the hyperleptinemia found in obesity could contribute to the insulin resistance. We investigated the effects of leptin on insulin binding by isolated adipocytes. Adipocytes isolated from Sprague-Dawley rats exhibited a dose-dependent reduction in the uptake of 125I-labelled insulin when incubated with various concentrations of exogenous leptin. For example, addition of 50 nM leptin reduced total insulin binding in isolated adipocytes by 19% (P < 0.05). Analysis of displacement curve binding data suggested that leptin reduced maximal insulin binding in a dose-dependent manner, but had no significant effect on the affinity of insulin for its binding site. We conclude that leptin directly inhibited insulin binding by adipocytes, and the role of leptin in the development of insulin resistance in obese individuals requires further investigation.

Adipocytes↗