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Biomedical subjects

R C O'Brien

Publications and source records attributed to R C O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1992

Antihypertensive therapy in a model combining spontaneous hypertension with diabetes.

We have compared the effects of the angiotensin converting enzyme inhibitor, perindopril, and a conventional antihypertensive regimen (triple therapy: hydralazine, reserpine and hydrochlorothiazide) on kidney function and albuminuria in hypertensive diabetic rats. Diabetes was induced with streptozotocin in spontaneously hypertensive (SHR) rats and they were randomized to receive no treatment, perindopril or triple therapy. Antihypertensive drugs were commenced at the time of induction of diabetes and continued for 16 weeks. Blood pressure reduction was equal in the groups treated with perindopril or triple therapy. All groups had similar severity of diabetes as determined by body weight, serum glucose and glycated hemoglobin levels. Whereas plasma renin activity rose in both the perindopril and triple therapy groups, it is likely that the effects on angiotensin II levels were opposite since perindopril but not triple therapy was associated with a significant reduction in plasma angiotensin converting enzyme activity. Diabetes was associated with an increase in glomerular filtration rate. At 12 weeks, glomerular filtration rate was higher in the perindopril treated group when compared to the triple therapy group, but neither group treated with antihypertensive therapy was different to untreated diabetic rats. Both drug regimens reduced albuminuria in the diabetic rats to a similar degree apparently independently of their effects on the renin-angiotensin system. Studies in diabetic subjects are warranted to evaluate different classes of antihypertensive drugs with respect to their effects on kidney function, proteinuria and glomerular morphology.

Albuminuria↗
PubMed1991

Comparison of sequential cyproterone acetate/estrogen versus spironolactone/oral contraceptive in the treatment of hirsutism.

The effects of the antiandrogen drugs cyproterone acetate (CPA) and spironolactone on hair growth and androgen levels were compared in a randomized study of 48 hirsute women. Twenty six subjects completed 6 months of therapy with 100 mg/day CPA and 19 subjects completed 6 months of 100 mg/day spironolactone. All except 10 subjects received concomitant estrogen therapy. Measured objectively, total hair diameter fell by 17.1% with spironolactone (P less than 0.001), and by 16.8% with CPA (P less than 0.001). The diameter of the hair medulla fell by 17.8% with spironolactone (P less than 0.01), and by 31.7% with CPA (P less than 0.001). There was no difference between the drugs in their effect on hair diameter. Plasma testosterone levels also fell significantly with both drugs. As a subjective assessment of treatment efficacy, the frequency with which subjects performed cosmetic measures was recorded. This fell by 38% with spironolactone and by 44.7% with CPA (P less than 0.001 both drugs), and again there was no difference between the drugs. Side effects caused cessation of treatment in one subject taking CPA and two subjects taking spironolactone, and milder side effects were noted in two further subjects from each treatment group. We conclude that spironolactone and CPA, in the dosages used in this study, are effective and well tolerated agents for the treatment of hirsutism, and that neither drug demonstrates a particular advantage over the other.

Adult↗
PubMed1990

Comparison of simvastatin and cholestyramine in the treatment of primary hypercholesterolaemia.

The effects of simvastatin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on plasma lipid levels were compared with those of the bile acid sequestrant cholestyramine in a randomized parallel study of 60 subjects with primary hypercholesterolaemia. After a 12-week direct comparison period 37 subjects with inadequate cholesterol reduction received a combination of both drugs and all subjects were followed for a further 40 weeks. Simvastatin was more effective than cholestyramine in lowering total and LDL cholesterol levels and the LDL/HDL ratio (-31.7% v. -19.7% [P less than 0.01], -41.0% v. -31.8% [P less than 0.05] and -46.7% v. -33.6% [P less than 0.01], respectively at Week 12). Only simvastatin significantly increased the HDL cholesterol concentration (+13.3% [P less than 0.01] v. +6.4%). Cholestyramine increased plasma triglyceride levels by 37.5% (P less than 0.01) whereas simvastatin caused a slight non-significant reduction. Combined therapy produced a further decrease in total and LDL cholesterol levels, and in the LDL/HDL ratio, which was sustained for the duration of the study. Simvastatin was better tolerated than cholestyramine (P less than 0.01), and combining the two drugs enhanced efficacy without increasing the frequency of side effects.

Adult↗
PubMed1990

The use of simvastatin, an HMG CoA reductase inhibitor, in older patients with hypercholesterolemia and atherosclerosis.

Epidemiological evidence suggests that elevated serum cholesterol, especially the low density lipoprotein (LDL) fraction, the total/high density lipoprotein (HDL)-cholesterol ratio, and the LDL/HDL-cholesterol ratio, remains a risk factor for atheromatous disease up to the age of 79 years. We studied the efficacy and tolerability of simvastatin, an HMG CoA reductase inhibitor, in 20 patients aged 65 to 75 years with clinical evidence of atheromatous disease. After four weeks of treatment, there was a 29% fall in LDL-cholesterol levels (P less than .01 vs placebo) with low dose simvastatin and a 38% fall with high dose simvastatin (P less than .001 vs placebo). Similar falls were seen in total cholesterol levels and the LDL/HDL-cholesterol and total/HDL-cholesterol ratios. Apoprotein B levels decreased by approximately 20% with both doses (P less than .05 vs placebo). In an open extension of the study, the decreases in lipid parameters were sustained for a further 48 weeks of treatment with doses of simvastatin ranging from 10 to 40 mg. Two patients required the addition of cholestyramine. Although a small study like this cannot establish safety and tolerance, side effects were minor and did not require stopping therapy in any patient. Simvastatin is an effective cholesterol lowering agent in older patients.

Aged↗
PubMed1990

Glomerular filtration rate in streptozocin-induced diabetic rats. Role of exchangeable sodium, vasoactive hormones, and insulin therapy.

The interrelationships of sodium and volume status, atrial natriuretic peptide (ANP), plasma renin activity (PRA), insulinlike growth factor I (IGF-I), and kidney weight and their influence on glomerular filtration rate (GFR) were investigated in rats during the first 4 wk of streptozocin-induced diabetes (STZ-D). In each of three experiments, untreated diabetic rats were compared with nondiabetic control rats and rats with varying degrees of glycemic control during insulin therapy. The first experiment evaluated exchangeable sodium, plasma volume, and GFR. In untreated diabetic rats, exchangeable sodium and plasma volume, but not GFR, were increased by approximately 25% compared with control rats. Insulin-treated diabetic rats with plasma glucose levels ranging from 12 to 30 mM had increased GFR, whereas exchangeable sodium and plasma volume were reduced toward control values. Daily insulin therapy, titrated to maintain euglycemia, further reduced exchangeable sodium and plasma volume and decreased but did not normalize GFR. The second experiment evaluated the relationship between vasoactive hormones and GFR. In untreated diabetic rats, plasma ANP levels increased 89% and urinary cyclic GMP (cGMP) excretion increased 94%, with an 85% decrease in PRA, whereas GFR was unchanged. Moderate hyperglycemia (plasma glucose 12-30 mM) was associated with normalized plasma ANP levels and urinary cGMP excretion, a 52% decrease in PRA, and a 13% increase in GFR. The third experiment studied serial changes in food and water intake and vasoactive hormones and end-point measurement of kidney weight, GFR, and plasma IGF-I. In the untreated diabetic group, urinary cGMP excretion was significantly elevated after 3 wk, whereas the reduction in PRA levels was apparent after 1 wk.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Nephropathy in model combining genetic hypertension with experimental diabetes. Enalapril versus hydralazine and metoprolol therapy.

We compared the effects of the angiotensin-converting enzyme inhibitor enalapril and a conventional antihypertensive regimen (hydralazine and metoprolol) on kidney function, albuminuria, and glomerular ultrastructure in hypertensive diabetic and nondiabetic rats. Diabetes was induced with streptozocin at 8 wk of age in spontaneously hypertensive (SHR) rats. Antihypertensive drugs were administered in drinking water from the time of induction of diabetes in all groups. Blood pressure reduction was equal in the diabetic and nondiabetic SHR rats receiving either enalapril or hydralazine plus metoprolol. In diabetic SHR rats, there was a rise in serum creatinine after 32 wk, which did not occur in diabetic rats treated with either antihypertensive regimen or in nondiabetic rats. Both drug regimens reduced albuminuria in diabetic and nondiabetic SHR rats to a similar degree. Enalapril and the combination of hydralazine and metoprolol were associated with decreased glomerular basement membrane thickness and glomerular volume in diabetic and nondiabetic SHR rats without significant effect on fractional mesangial volume. Thus, antihypertensive therapy retards the development of albuminuria, glomerular basement membrane thickening, and glomerular hypertrophy in the rat in the presence or absence of diabetes. No specific benefit of angiotensin-converting enzyme inhibition was observed in these hypertensive models of nephropathy. Human studies comparing the effects of different classes of antihypertensive drugs on kidney function, proteinuria, and glomerular morphology are warranted.

Administration, Oral↗
PubMed1989

Ramipril reduces albuminuria in diabetic rats fed a high protein diet.

1. Streptozotocin diabetes was induced in Wistar-Kyoto rats fed a 50% protein diet. Animals were randomized to receive either the ACE inhibitor ramipril, 1 mg/L in drinking water (n = 7), or no treatment (n = 7) and were studied for 6 months. Blood glucose, body weight and glomerular filtration rate (GFR) were measured at 0, 1, 4, 8 and 16 weeks of diabetes and urinary albumin excretion was measured every 8 weeks. 2. In both groups, GFR increased significantly within 1 week of induction of diabetes (P less than 0.001) and thereafter remained stable. There was no difference in GFR between the treated and untreated groups. 3. Urinary albumin excretion increased progressively in both groups throughout the study. Ramipril treatment reduced albuminuria by approximately 50% at weeks 16 and 24 (P less than 0.01). 4. The amelioration of diabetic albuminuria by ACE inhibition, in the setting of high dietary protein intake, may have important implications for the treatment of human diabetic nephropathy.

Albuminuria↗
PubMed1988

A pharmacological study of hibernation in rodents.

1. Hamsters and ground squirrels in deep hibernation were infused intra-arterially with drugs. 2. Norepinephrine and epinephrine sometimes caused arousal, sometimes transitory effects. 3. Adrenalectomy did not affect arousal. L-DOPA and amphetamine produced a slow arousal. 4. Arousal was blocked with alpha-methyltyrosine and the block was released with L-DOPA, DL- and L-threo-DOPS resulted in arousal and bromocriptine did not cause arousal, indicating that dopamine was not necessary for arousal. 5. Isoproterenol caused a transient increase in heart rate which was blocked by propranolol. 6. Phenylephrine caused vasoconstriction, but did not result in arousal. 7. No drug increased the sensitivity to peripheral stimuli during hibernation.

Adrenalectomy↗
PubMed1988

Effects of genetic hypertension on diabetic nephropathy in the rat--functional and structural characteristics.

Streptozotocin (STZ) diabetes was induced in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Body weight, blood pressure, renal function, glycaemic control and proteinuria were assessed monthly for 32 weeks. At 32 weeks, the animals were killed and glomerular basement membrane (GBM) thickness and fractional mesangial volume were measured. There was no significant difference in renal function between diabetic SHR and diabetic WKY. Diabetic SHR showed an earlier and larger rise in total proteinuria and urinary albumin excretion than diabetic WKY. Urinary albumin excretion was increased more than tenfold in diabetic SHR compared to diabetic WKY after 32 weeks of diabetes. GBM thickness was significantly increased in diabetic SHR compared with diabetic WKY. Both diabetic WKY and diabetic SHR showed mesangial expansion when compared to their nondiabetic counterparts. On the other hand, both hypertensive models showed increased glomerular volume, which was not influenced by the presence of diabetes. The diabetic SHR model has features of accelerated nephropathy, as evidenced by increased albuminuria and GBM thickness. This suggests that pre-existing hypertension may play an important role in the progression of diabetic renal disease.

Animals↗
PubMed1976

Quantitative relationship of fecal asbestos to asbestos exposure.

A method is descirbed for isolating chrysotile fibers from feces and counting them with an electron microscope. The detection limit was 150,000 fibers per gram feces; average recovery was 85.5%. When the method was used to check the asbestos in feces of people subjected to industrial exposure vs. controls, the means were significantly different (p less than 0.02). Duplicate fecal samples were found to check within an average of +/- 31.1% of their means.

Asbestos↗