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Biomedical subjects

T W Wilson

Publications and source records attributed to T W Wilson.

At least 91 records · Page 5Linked to original sources
PubMed1987

Effect of cyclooxygenase and thromboxane synthetase inhibition on furosemide-stimulated plasma renin activity.

We studied the effects of a specific thromboxane (TX) synthetase inhibitor (U-63,557A) and a cyclooxygenase inhibitor on furosemide-induced renin release. Furosemide (2.0 mg X kg-1) was injected into Sprague-Dawley rats pretreated with indomethacin (10 mg X kg-1, i.v.), U-63,557A (1.0-32.0 mg X kg-1, i.v.), or vehicle (Na2CO3 0.03 M). Plasma renin activity was measured in blood samples collected 0, 10, 20, and 40 min after the injection of furosemide. Blood was also collected after the administration of vehicle, indomethacin, or U-63,557A for serum TXB2, a measure of platelet TXA2 synthesis. The results demonstrated that plasma renin activity rose with time following furosemide in the various groups of rats; indomethacin suppressed the furosemide-induced increments in plasma renin activity, while U-63,557A at doses of 4-8 mg X kg-1 augmented it. At doses below 4 mg X kg-1 or above 8 mg X kg-1, U-63,557A did not augment renin secretion. Indomethacin and U-63,557A reduced serum thromboxane by 81 and 90%, respectively. Thus, these experiments suggest that thromboxane synthetase inhibition, within a narrow dosage range, potentiates furosemide-induced renin release while cyclooxygenase inhibition suppresses it.

Animals↗
PubMed1987

Characterization of polydimethacrylates and their composites by dynamic mechanical analysis.

The objective was to characterize, by dynamic mechanical analysis (DMA), the polymeric materials used to restore teeth and, in particular, to assign a glass transition temperature, Tg. Generally, in DMA work, Tg is taken as the temperature at which the internal damping, i.e., tan delta, has a maximum value. However, in the present work it was shown that the classical method of assigning Tg corresponds more closely to an assignment based on changes in elastic modulus. On this basis, a bis-GMA copolymer and a proprietary dental composite, both polymerized by exposure to light, were assigned Tg values of -25 degrees C and +10 degrees C, respectively. The composite had an even lower value, Tg = -10 degrees C, after saturation with water. The value of Tg can be increased considerably by treatments which are known to increase the degree of polymerization, i.e., by heating or by gamma-irradiation. The present findings imply that composites made by photopolymerization may undergo marked changes in mechanical state (becoming glassy, leathery, and rubbery) in the oral cavity, due to changes in temperature from about 0 degree C to 50 degrees C. It is not known which of these states would give best service properties, such as wear resistance, but in any case variation of properties in service would appear to be undesirable.

Bisphenol A-Glycidyl Methacrylate↗
PubMed1986

History of salt supplies in West Africa and blood pressures today.

Excess salt consumption has been implicated in the rising prevalence of essential hypertension in West Africa. It has been suggested that low supplies of salt in West African history were responsible for a genetic mutation that predisposes Blacks to high blood pressure. However, historical evidence concerning salt supplies in West Africa suggests that availability was not uniform. For instance, in Senegal and Gambia salt production has been extensive since ancient times, whereas in ancient Nigeria the population had to depend on local vegetables salts or meagre imports of the mineral. Reports that blood-pressures in Senegalese and Gambians are lower than those in Nigerians may be a reflection of historical differences in salt supply. The difference in blood pressure between members of a racial group also casts serious doubt on the concept of racial homogeneity often accepted in the medical sciences, and the relation between blood-pressure and salt availability in West Africa reveals that insights can be obtained from a study of history.

Africa, Western↗
PubMed1986

Effects of low-dose aspirin on responses to furosemide.

We assessed the effects of low-dose aspirin (0.5 and 15 mg/kg/d) on renal prostaglandin synthesis and action in healthy volunteers using intravenous furosemide as a stimulus. Inhibition of platelet cyclo-oxygenase was assessed by changes in serum thromboxane B2 (TXB2) level. After one week of treatment, ten healthy subjects did not show any change in weight, blood pressure, or diuretic and natriuretic responses to furosemide with either dose of aspirin. Serum TXB2 level was reduced to 3% of control by aspirin 0.5 mg/kg/d and to 0.1% by the higher dose. In contrast, urine excretion of TXB2 was only reduced to 68% and 51% of the placebo value, whereas 6-keto-prostaglandin F1 alpha (6kPGF1 alpha) excretion was not decreased by either dose. Furosemide produced a transient increase in excretion rates of TXB2 and 6kPGF1 alpha that was of lesser duration than the diuretic response. These transient increases were slightly reduced by aspirin. Baseline plasma renin activity was not affected by either dose of aspirin. The brisk increment in plasma renin activity seen ten minutes after furosemide, as well as later values (30 and 240 min) were not changed by aspirin. We conclude that chronic low-dose aspirin can profoundly affect platelet PG production without affecting stimulated renal PGI2 production or plasma renin activity. There is a modest reduction in urine TXB2 excretion that is consistent with a primarily renal source of this metabolite.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The association of congenital ptosis and congenital heart disease.

Congenital ptosis and congenital heart disease are known to occur simultaneously in the presence of several well-recognized clinical syndromes. We report seven cases of documented, structural congenital heart defects found among 156 consecutive congenital ptosis patients operated at the Wills Eye Hospital. The possibility that the concurrence found in the patients was a manifestation of a dysmorphic syndrome was carefully excluded by observers skilled in the recognition of such anomalies. The observed rate of congenital heart disease, in otherwise normal congenital ptosis patients, was five times the expected rate in the pediatric population at large. This should alert ophthalmologists examining pediatric ptosis patients to the possibility of a coexisting structural heart defect.

Adolescent↗
PubMed1986

The antihypertensive action of hydrochlorothiazide and renal prostacyclin.

To investigate whether chronic hydrochlorothiazide (HCTZ) therapy increases synthesis of tissue vasodilator prostaglandins (PG), we used intravenous furosemide as a standardized stimulus of renal PG synthesis before and after HCTZ dosing. Sixteen subjects with mild hypertension received placebo for 4 weeks, followed by HCTZ, 50 mg/day, and potassium chloride, 60 mmol/day, for 4 weeks. Nine subjects had decreased mean arterial pressure (-12.2 +/- 0.9 mm Hg) after HCTZ (responders), while seven others had no antihypertensive effect (nonresponders). Responders increased their excretion of the prostacyclin (PGI2) hydrolysis product 6-keto-PGF1 alpha in the first 10 minutes after furosemide, from 17.8 +/- 2.7 ng after placebo to 34.9 +/- 7.5 ng (P less than 0.05) after HCTZ, whereas nonresponders showed no such increase. These groups could not be distinguished on the basis of sex, age, or pretreatment plasma renin activity. After HCTZ dosing, responders showed evidence of increased action of PGI2 by increased plasma renin activity 10 minutes after furosemide (6.10 +/- 1.06 vs. 3.39 +/- 0.4 ng/ml/hr; P less than 0.05). Furthermore, creatinine clearance was maintained in responders (while decreasing slightly in nonresponders) despite lower blood pressure, a finding consistent with increased vasodilator effect. We conclude that an antihypertensive response to HCTZ is accompanied by an increase in renal PGI2 synthesis and action.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effects of indomethacin on furosemide induced renal prostaglandin synthesis and action in man.

We had previously shown that the early increment in plasma renin activity occurring within ten minutes of intravenous furosemide is accompanied by an increase in urine 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) the hydrolysis product of prostacyclin. Renal prostacyclin and thromboxane A2 synthesis are apparently limited to the cortex. To assess whether indomethacin would inhibit renal cortical eicosanoid synthesis and whether such reduction correlated with reduced early renin release, we assessed responses to intravenous furosemide (0.5 mg/kg) before and after indomethacin (150 mg/day for seven days) in ten normal male volunteers. Indomethacin did not change blood pressure but increased weight slightly (79.7 +/- 2.5 kg to 80.4 +/- 2.4 kg, p less than 0.05). Serum thromboxane B2 (TXB2), a measure of platelet thromboxane A2 production, was profoundly depressed (142 +/- 29 ng/ml to 4.8 +/- 1.6 ng/ml, p less than 0.001). Neither diuresis nor natriuresis were changed by indomethacin but potassium excretion was reduced (33 +/- 4 mmol/4 hr to 27 +/- 3 mmol/4 hr, p less than 0.05). Basal as well as furosemide stimulated plasma renin activity (at 10, 30 and 240 minutes) was reduced, as well as the transient increase in excretion rates of 6-keto-PGF1 alpha and TXB2. We conclude that the reduction in furosemide stimulated renin release by indomethacin is due to renal cyclo-oxygenase inhibition which is reflected in decreased excretion rates of hydrolysis products of renal eicosanoids.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Silsoft extended wear contact lenses in pediatric aphakia.

Fifty pediatric aphakic patients, ranging in age from 7 days to 11 years, were fitted with the Silsoft extended wear contact lens. Compared to other extended wear lenses, the Silsoft lens has several advantages. These include easier handling, a less traumatic fitting procedure for the child, the use of fluorescein for evaluation of the lens-cornea relationship and a low loss rate. This lens appears to be safe, with no permanent adverse effects on the cornea.

Aphakia, Postcataract↗
PubMed1985

Low plasma renin activity in diabetes. Relation to urine prostaglandin excretion.

Renal functional abnormalities, occurring before overt renal disease and possibly due to abnormal vascular control mechanisms, have been described in diabetes mellitus. We used intravenous (i.v.) furosemide, which stimulates renal prostaglandin (PG) synthesis and renin release, to compare these vasoactive systems in 14 diabetic and 23 normal control subjects. Using urine thromboxane B2 (TXB2) as an index of renal synthesis of the vasoconstrictor prostanoid TXA2, and urine 6keto-PGF1 alpha for the vasodilator PGI2, we found evidence of increased renal TXA2 synthesis in diabetic subjects in response to furosemide. The increased TXA2 synthesis did not occur at the expense of PGI2 synthesis, as urine 6keto-PGF1 alpha was not reduced. Increased TXB2 excretion in diabetic subjects was particularly marked in the first 10 min after i.v. furosemide. During this time, diabetic males excreted 31 +/- 6 ng of TXB2 compared with 10 +/- 1 ng for normal males (P less than 0.05), while diabetic females excreted 15 +/- 3 ng compared with 7 +/- 1 ng for normal females (P less than 0.05). Also, 6keto-PGF1 alpha excretion at 10 min was increased in diabetic subjects: males, 29 +/- 3 ng versus 19 +/- 3 (P less than 0.05); females, 33 +/- 8 versus 16 +/- 3 (P less than 0.05). The ratio of TXB2 to 6keto-PGF1 alpha tended to be higher in diabetic males.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Designing education interventions to improve physician performance in office practice.

Family doctors play a very important role in determining the health of the populace; however, surveys and expert opinions indicate that there is considerable room for improvement in the knowledge and skills of family physicians concerning the prevention, early detection and management of the major causes of death and disability. Effective Continuing Medical Education (CME) could help greatly to resolve this problem. THere is, however, little evidence that presently available systems of CME, though costly, are effective in improving either physician competence or patient health. Attractive and cost-effective CME methods are greatly needed. This study develops, field tests and evaluates more efficient office-based CME programs for family doctors. Prevention, early detection and improved management of cardiovascular disease and cancer are the primary goals. A pretest posttest control group and time series approach was chosen for the experimental design. Thirty-one family physicians are participating. Physician performance and patient outcome prior to and after education are being assessed largely through office record review.

Education, Medical, Continuing↗
PubMed1983

Amantadine-dyazide interaction.

To document an interaction between amantadine hydrochloride and Dyazide that had apparently produced amantadine toxicity, a patient was given amantadine alone for 1 week, followed by amantadine plus Dyazide for another week, under controlled conditions. A diuretic effect was observed after Dyazide was added to the regimen, but the urine amantadine excretion fell, and the drug's plasma concentration increased. It was concluded that one or both of the components of Dyazide (hydrochlorothiazide and triamterene) reduce the clearance of amantadine and can produce higher plasma concentrations and toxic effects.

Amantadine↗
PubMed1983

Responses to furosemide in normotensive and hypertensive subjects.

As well as inducing natriuresis, intravenous furosemide increases renal prostanoid synthesis and induces renal vasodilation and a rapid rise in plasma renin activity (PRA). Patients with hypertension have abnormalities in renin release and renal vascular resistance that might be due to abnormalities in renal prostaglandin synthesis. We investigated responses to furosemide and placebo in normotensive (n = 13) and hypertensive (n = 14) subjects. There were no clear differences in PRA, sodium and water excretion, or excretion of prostanoid hydrolysis products (6-ketoprostaglandin F1 alpha and thromboxane B2) after placebo. In the hours after furosemide, 0.5 mg/kg-1, hypertensive subjects excreted more sodium, 189 +/- 13 mEq (mean +/- SE) and 154 +/- 8, and water, 1990 +/- 116 ml and 1614 +/- 109, than normotensive subjects. Excretion rates of creatinine and 6-ketoprostaglandin F1 alpha were much the same. Thromboxane B2 excretion rose in hypertensive subjects and was greater than in normotensive subjects (117.6 +/- 17.2 and 58.3 +/- 8.2 ng). With timed urine samples the excretion rate of 6-ketoprostaglandin F1 alpha and thromboxane B2 increased transiently for 30 min or less, whereas sodium and water excretion rates remained elevated for 4 hr. PRA rose in both groups 10 min after injection but reached a higher level in normotensive subjects. These differences in excretion of prostanoid hydrolysis products likely reflect renal synthesis of prostanoids and may be responsible for functional abnormalities of the kidney of hypertensive patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Timolol and propranolol: bioavailability, plasma concentrations, and beta blockade.

Timolol, like propranolol, is a nonselective beta-adrenergic blocker, but it is much less lipid soluble and is formulated as a single enantiomer rather than a racemic mixture. We examined the effects of such differences on bioavailability, systemic clearance, and pharmacologic response. Ten healthy subjects received placebo, 0.2 mg/kg IV propranolol, 3.2 mg/kg oral propranolol, 0.025 mg/kg IV timolol, and 0.4 mg/kg oral timolol in double-blind, randomized crossover fashion. Plasma concentrations of total drug were monitored up to 8 hr, while responses to submaximal exercise were measured at 0, 2, and 6 hr. Timolol had greater bioavailability (F = 0.61 +/- 0.06(SEM) and 0.32 +/- 0.04) and lower systemic clearance (463 +/- 74 ml kg-1 hr-1 and 1040 +/- 120 ml kg-1 hr-1) than propranolol. Half-lifes were of the same order (2.7 and 2.9 hr). There was a marginal correlation between areas under the intravenous and oral plasma concentration-time curves for timolol (r = 0.66, P = 0.054), but none for propranolol (r = 0.48, P NS). There were also correlations of the response (percent reduction in heart rate) to oral and intravenous timolol at 2 hr (r = 0.72, P less than 0.05) and 6 hr (r = 0.84, P less than 0.01) hr, but none between responses to oral and intravenous propranolol. Finally, the response to oral timolol was related to the area under its plasma concentration-time curve, whereas that to propranolol was not. We conclude that the physicochemical properties of timolol lead to greater bioavailability. Pharmacologic response to an oral dose of timolol, unlike that to propranolol, can be predicted from the response to an intravenous dose and reflects its plasma concentration.

Administration, Oral↗
PubMed1978

Improving physician performance by continuing medical education.

In 1973 the division of continuing medical education of the University of Saskatchewan initiated a 3-year study to determine the effect of hospital-based education on the prescribing accuracy of physicians. This study was undertaken in response to an urgent need to develop more effective methods of continuing medical education and improved techniques of measuring their effectiveness. The educational program focused on common prescribing problems that had previously been defined by experts in the field. Problem frequency was determined by the monitoring of hospital records prior to institution of the educational program and at 3, 6 and 12 months after the program had concluded; this was found to be a satisfactory method of identifying educational needs and is considered to provide a measure of the quality of medical care. Fifteen physicians at three rural hospitals participated in the study. Seventeen physicians at two similar hospitals served as controls. The average problem frequency for topics selected at the study hospitals was reduced by 63% (the percentage of possible improvement), whereas at the control hospitals the frequency of the same problems declined by 32% over the same period. The results of this study provide evidence that an intensive, problem-based program on therapeutics can improve physician performance.

Drug Prescriptions↗