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Biomedical subjects

L Wilder

Publications and source records attributed to L Wilder.

9 recordsLinked to original sources

Protection of glomerular filtration rate by the thromboxane receptor antagonist L655,240 during low dose cyclosporine administration.

Cyclosporin A (CsA) alters the production of prostaglandins (PG) by the kidney. CsA causes an increase in renal vascular resistance, a decrease in renal blood flow, a decrease in glomerular filtration rate (GFR), and increases the renal production of the vasoconstrictor thromboxane. Recently, low dose CsA has been utilized in the treatment of refractory autoimmune diseases. To determine if low dose CsA administration could produce renal hemodynamic alterations and to determine if the thromboxane receptor antagonist L655,240 could prevent these alterations, we administered groups of rats either CsA, 5 mg/kg, subcutaneously and the L655,240 vehicle NaHCO3 (CsA-NaHCO3), or CsA and L655,240 (CsA-L655,240), or CsA vehicle and L655,240. The rats were administered the drugs for 7 days and then subjected to inulin and PAH clearances or kidneys were harvested for prostaglandin production studies. CsA significantly depressed GFR and renal plasma flow when compared to the L655,240 treated groups. There was no difference in inulin or PAH clearance between the CsA-L655,240 and CsA vehicle L655,240 groups. Glomerular prostaglandin production including thromboxane was depressed by CsA administration. No histologic alterations were noted in the glomeruli or the medullary portions of the kidney. We conclude that administration of low dose CsA, 5 mg/kg, for 7 days results in a decrease in renal blood flow and GFR without histologic alterations. Administration of the thromboxane receptor antagonist L655,240 prevents the renal hemodynamic alterations induced by CsA in this rat model.

Animals↗

Lipid-lowering diets in patients taking pravastatin, a new HMG-CoA reductase inhibitor: compliance and adequacy.

We examined seven 1-d diet records kept during 1 y by 272 men and women instructed to follow a lipid-lowering diet while participating in a clinical trial of pravastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. The mean percentage of calories from total fat and saturated, unsaturated, and monounsaturated fatty acids was similar throughout the year even though the patients knew they were taking an effective lipid-lowering agent. However, the diets of greater than 40% of women included less than two-thirds of the recommended dietary allowance (RDA) of folic acid, vitamins B-6 and D, and calcium and zinc; in men, folic acid and zinc intakes were low. We conclude that patients comply with lipid-lowering diets even when they know that they are receiving an effective serum lipid-lowering agent. However, for both men and women special attention should be given to the intake of several nutrients.

Adult↗

The effect of cyclosporine on agonist-stimulated glomerular and mesangial cell vasodilatory prostaglandin production.

Cyclosporine A administration produces an increase in renal vascular resistance and a decrease in glomerular filtration rate in both human and animal models. CsA usage in humans has also been shown to alter the ability of the kidney to adapt to alterations in renal hemodynamics. CsA alters the production of prostaglandins by isolated rat glomeruli. Normally, vasoconstrictive agents stimulate the production of vasodilatory glomerular and mesangial cell PG. To determine if CsA alters glomerular and mesangial cell (MC) vasodilatory PG production in response to vasoconstrictive agents, we administered CsA, 20 mg/kg, or vehicle to rats for 7 days, or incubated mesangial cells with CsA 1 mcg/ml for 24 hr. Ex vivo glomerular PGE2 and 6-keto-PGF1a production was determined in the presence or absence of angiotensin II 10(-6) M and norepinephrine 10(-5)M. CsA administration decreased glomerular production of both eicosanoids in the basal and stimulated state. Incubation of MC with CsA markedly suppressed PGE2 and 6-keto-PGF1a production in response to stimulation with 200 nM angiotensin II. To determine if CsA inhibits angiotensin II-stimulated PG production prior to protein kinase C, we incubated glomeruli and MC with the diacylglycerol mimetic OAG. CsA depressed OAG-stimulated glomerular and MC PGE2 and 6-keto-PGF1a production. Conversely, CsA stimulated the production of PGE2 by renal medullary slices. We conclude that CsA blunts the vasoconstrictor-induced increase in glomerular and mesangial cell vasodilatory PG production, thereby removing a compensatory mechanism that maintains GFR in states of vasoconstrictor excess.

6-Ketoprostaglandin F1 alpha↗

Overt and covert verbalization in normal and learning disabled children's problem solving.

The problem-solving ability of 18 learning-disabled high school students was increased by instructions to verbalize overtly, but not by instructions to verbalize their actions covertly. This suggests that Vygotsky's 1962 "internalization-of-speech" perspective may be as useful in understanding the limitations of disabled learners as it has been in understanding the limitations of young learners.

Adolescent↗

Human exposure to elemental mercury in a contaminated residential building.

Residents of a condominium building in Hoboken, New Jersey, were exposed to mercury contamination in indoor air. Elevated levels of mercury were detected in urine samples provided by the residents, and 69% of the urine mercury levels were 20 microg/l or greater. Urine mercury levels were correlated positively with the duration of residency in the building and with the time (i.e., h/d) residents spent in the building. Environmental and biomonitoring data indicated that the residents were being exposed to mercury levels that were cause for health concern. Local health authorities, therefore, declared the building to be unfit for habitation and ordered that the premises be vacated. Health officials monitored the personal belongings of residents for mercury contamination before the items were removed from the building. The residents were offered medical evaluations and support services as part of the relocation effort.

Adult↗

Prevalence of hypercholesterolemia among siblings of persons with premature coronary heart disease. Application of the Second Adult Treatment Panel guidelines.

BACKGROUND: Increased blood cholesterol, specifically high low-density lipoprotein cholesterol, increases risk for coronary heart disease (CHD). Persons with a positive family history of premature CHD also are at markedly increased risk. OBJECTIVE: To examine the prevalence of hypercholesterolemia based on the second report of the National Cholesterol Educational Program Adult Treatment Panel (ATP II) guidelines in the asymptomatic healthy siblings of people with premature CHD. METHODS: A total of 668 asymptomatic healthy siblings (354 men and 314 women) underwent screening for risk factors for CHD. Siblings were categorized into treatment categories for primary prevention defined by ATP II. The percentage who were candidates for intervention were compared with the published national estimates for those without CHD from the third National Health and Nutrition Examination Survey (NHANES III). RESULTS: Based on ATP II guidelines, 65% of the asymptomatic adult siblings required fasting lipoprotein analysis compared with 33% of adults without CHD in the national reference population. Of the siblings who met the criteria for fasting lipoprotein analysis, most (56%) were candidates for dietary therapy, more than twice the proportion of adults from NHANES III. The percentage of the siblings who qualified for drug intervention and dietary therapy was 3 times greater than the national sample, 33% vs 11%, respectively. Assuming a 10% hypothetical reduction in low-density lipoprotein cholesterol levels as the result of dietary modification, the proportion of the sibling sample who were possible candidates for drug therapy was 20%, still 4 times that predicted for the national sample. CONCLUSIONS: These results underscore the need for aggressive detection and treatment of hypercholesterolemia in this easily identifiable high-risk population of siblings of people with premature CHD.

Adult↗