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Showing papers by "Mark E. Cooper published in 1991"


Journal ArticleDOI
01 Oct 1991-Diabetes
TL;DR: The concomitant changes in collagen-related fluorescence, albuminuria, and mesangial expansion with aminoguanidine therapy are consistent with the hypothesis that AGEs may play a role in the development of diabetic nephropathy.
Abstract: This study evaluated the relationship between the development of fluorescence related to advanced glycosylation end products (AGEs) in the kidney and experimental diabetic nephropathy over a 32-wk period. Control, untreated diabetic, and aminoguanidine-treated diabetic rats were followed for 32 wk with eight weekly measurements of urinary albumin excretion. After 32 wk, collagen-related fluorescence in aorta and kidney (whole kidney, isolated glomeruli, and renal tubules) and glomerular ultrastructure were evaluated. Diabetes was associated with a significant increase in collagen-related fluorescence in the aorta and kidney. Aminoguanidine prevented the increases in collagen-related fluorescence in aorta, isolated glomeruli, and renal tubules but not in whole kidney. Diabetes was associated with increased albuminuria, fractional mesangial volume, and glomerular basement membrane (GBM) thickness. Aminoguanidine attenuated the rise in albuminuria and prevented mesangial expansion without influencing GBM thickness in diabetic rats. The concomitant changes in collagen-related fluorescence, albuminuria, and mesangial expansion with aminoguanidine therapy are consistent with the hypothesis that AGEs may play a role in the development of diabetic nephropathy.

464 citations


Journal ArticleDOI
TL;DR: There may be a qualitative distinction between responders and nonresponders to dopamine antagonists in schizophrenic patients who improve with administration of neuroleptic drugs but not in patients who fail to display a treatment response.
Abstract: • Measurement of plasma concentrations of the dopamine metabolite, homovanillic acid, is an indirect tool to assess changes in dopamine turnover in schizophrenic patients. Plasma homovanillic acid concentrations have been reported to decrease during neuroleptic treatment, with the decrement correlating with symptomatic improvement in symptoms of schizophrenia. The present study tested the hypothesis that neuroleptic drugs decrease plasma homovanillic acid concentrations in those schizophrenic patients who improve with administration of neuroleptic drugs but not in patients who fail to display a treatment response. Twenty schizophrenic men who remained drug free for at least 2 weeks were treated with 20 mg/d of haloperidol for 5 weeks. Symptoms and plasma homovanillic acid concentrations were assessed on the last drug-free day and weekly for 5 weeks. Mean plasma homovanillic acid concentrations decreased in the group of patients who responded to neuroleptic treatment and did not change in the group of patients who did not improve. These findings suggest that there may be a qualitative distinction between responders and nonresponders to dopamine antagonists.

74 citations


Journal ArticleDOI
TL;DR: It is concluded 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.
Abstract: 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.

64 citations


Journal ArticleDOI
TL;DR: The administration of aldose reductase inhibitors from the time of induction of diabetes significantly reduces glomerular prostaglandin production and urinary albumin excretion in diabetic rats, although it remained elevated compared with non-diabetic rats.
Abstract: The effect of two structurally unrelated aldose reductase inhibitors, sorbinil and ponalrestat, on glomerular prostaglandin production and urinary albumin excretion was investigated in rats with diabetes induced by streptozotocin. It was found that both aldose reductase inhibitors, when administered from the time of induction of the diabetes, significantly decreased the raised urinary albumin excretion in the diabetic rats, although it remained elevated compared with non-diabetic rats. Glomerular prostaglandin E and 6-ketoprostaglandin F1α production was significantly increased in glomeruli obtained from the diabetic rats. Inhibition of aldose reductase caused a reduction in the raised glomerular prostaglandin production, although this remained above that observed in the non-diabetic rats. Subsequent experiments were performed to determine whether the effects of the aldose reductase inhibitors could be explained by effects on glomerular filtration rate. It was found that ponalrestat, at a dose which markedly reduced urinary albumin excretion, did not significantly affect glomerular filtration rate in non-diabetic rats, rats with untreated streptozotocin-induced diabetes and rats with diabetes partially treated with low dose insulin. Glomerular sorbitol concentrations were significantly elevated in untreated diabetic rats as early as two weeks after the induction of diabetes. It is concluded that the administration of aldose reductase inhibitors from the time of induction of diabetes significantly reduces glomerular prostaglandin production and urinary albumin excretion. The latter effect is not due to an effect on glomerular filtration rate. Increased polyol pathway activity may account in part for the increased glomerular prostaglandin production and urinary albumin excretion in early experimental diabetes.

56 citations


Journal ArticleDOI
TL;DR: A cross-sectional survey of an age- and sex-stratified random sample of the elderly population living in Southampton was undertaken, measuring the frequency of cardiovascular disease by questionnaire and examination, and assessing cardiac anatomy and physiological function by noninvasive methods.
Abstract: A cross-sectional survey of an age- and sex-stratified random sample of the elderly population living in Southampton was undertaken with the object of measuring the frequency of cardiovascular disease by questionnaire and examination, and assessing cardiac anatomy and physiological function by noninvasive methods. The response rate was 64% and 259 men and women aged between 65 and 95 years were interviewed and examined and had a twelve-lead ECG and chest radiograph. Forty per cent of men and 47% of women reported a diagnosis of one or more cardiovascular diseases, of which high blood pressure 33%, coronary heart disease 14% (angina pectoris 11% and myocardial infarction 8%), peripheral arterial disease of the lower limbs 7%, and cerebrovascular disease 6% occurred most frequently. With the exception of high blood pressure, which women reported more frequently than men (40% vs 27%), the prevalence of these diagnoses by sex was similar. The self-administered WHO questionnaires gave point prevalence estimates for angina pectoris of 13%, possible myocardial infarction 7% and intermittent claudication 5%, which were similar to reported prevalences of these diseases, although disagreement in the classification of individuals for each disease was common. When comparing the WHO chest pain questionnaire with the doctors' independent diagnosis of angina pectoris in this population, the sensitivity of the WHO questionnaire was 79%, with a specificity of 98% and a predictive value of 88%. For each sex the sensitivity of the WHO chest pain questionnaire was similar but specificity and predictive value were both lower for women.(ABSTRACT TRUNCATED AT 250 WORDS)

30 citations


Book
01 Jan 1991
TL;DR: New diagnostic techniques in the acute abdomen injuries to the liver and bile ducts, J.E.Terblanche and J.J.Keighley acute cholecystitis, calculous and acalculous, R.R.Shoetz Jr manifestations of appendicitis, M.L.Walt peptic ulcer haemorrhage, K.N.Stower septicaemic shock.
Abstract: New diagnostic techniques in the acute abdomen injuries to the liver and bile ducts, J.Terblanche and J.E.J.Krige injuries to the spleen and pancreas, B.F.Gilchrist and D.D.Trunkey fracture of the pelvic ring, L.Solomon and M.J.Stower septicaemic shock, M.S.Dahn and A.J.Walt peptic ulcer haemorrhage, K.E.Wheatley and M.R.B.Keighley acute cholecystitis, calculous and acalculous, R.C.N.Williamson early management of acute gallstone pancreatitis, M.J.McMahon surgical complications of acute pancreatitus, E.L.Bradley III adhesion obstruction of the small bowel, M.Lavelle-Jones and A.Cuschieri malignant obstruction of the large bowel, A.R.Berry and N.J.Mortensn colonic pseudo-obstruction, S.Paterson-Brown and H.A.F.Dudley complications of the small bowel diverticula, W.E.G.Thomas colonic perforation, D.J.Shoetz Jr manifestations of appendicitis, M.J.Cooper gynaecological causes of the acute abdomen, M.E.Setchell and P.L.Cass mesenteric ischaemia, L.W.Ottinger ruptured abdominal aneurysms, R.J.Lusby and D.Huber.

12 citations