Short term blood pressure and metabolic effects of tibolone in postmenopausal women with non-insulin dependent diabetes.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M D Feher.
Explore the source record for details and available documents.
A community-based survey was undertaken to ascertain current hormone replacement therapy (HRT) prescription rates in postmenopausal diabetic women. From age/sex and disease registers linked to prescription data which covered 144,237 patients, details on 6867 women aged 50-60 years were obtained. Of this group, 1684 (24.5%) were receiving prescriptions for HRT; the comparable figures for the 537 patients with hypertension and 135 (insulin-dependent and non-insulin dependent) diabetic patients were 117 (21.8%) and 15 (11.1%) respectively. While the presence of hypertension did not affect the likelihood of being prescribed HRT (odds ratio 0.85 [95% CI 0.68-1.05], p > 0.1), women with diabetes were less than half as likely as those from the general population to be prescribed HRT (odds ratio 0.38 [95% CI 0.21-0.67], p < 0.001). These data indicate that proportionately greater numbers of postmenopausal diabetic women, even compared with those with hypertension, another group at high risk of cardiovascular disease, are denied the potential benefits of HRT.
Explore the source record for details and available documents.
OBJECTIVE: To evaluate the long-term safety profile of treatment with a statin-fibrate combination in a cohort of patients with documented coronary artery disease. DESIGN: Retrospective cohort analytical study. SETTING: District general hospital. PATIENTS: 102 (81 male and 21 female) hypercholesterolaemic (total cholesterol concentration > 6.5 mmol/l) patients with documented coronary artery disease and who had been treated with a statin-fibrate combination for over 1 year. Coronary artery disease was confirmed by angiography in 93 patients and by a positive (Bruce protocol) exercise test in the remainder. Fifty eight patients had a history of previous coronary bypass graft surgery. INTERVENTIONS: Twice daily lipid lowering treatment was given, with the fibrate administered in the morning (either bezafibrate 400 mg (n = 101) or fenofibrate 200 mg (n = 1)) and the statin in the evening (either simvastatin 10 mg (n = 23), 20 mg (n = 72), or 40 mg (n = 2) or pravastatin 10 mg (n = 1) or 20 mg (n = 4)). Treatment continued for 1 (n = 9), 2 (n = 58), or 3 (n = 35) years. MAIN OUTCOME MEASURES: Selected laboratory variables (total cholesterol concentration and liver (aspartate transaminase (AST)) and muscle enzyme (creatine kinase (CK)) activities) and documented symptomatology. RESULTS: A mean (SD) total cholesterol concentration of 5.2 (0.8) mmol/l was achieved after combined treatment for 1 year which was maintained at annual follow up. Over a maximum 3 year follow up no patient reported myalgic symptoms and none had a measured CK activity > 10 times above nomal. Four men on a simvastatin-bezafibrate combination had a CK activity rise to less than three times normal. Fourteen patients with a negative history of alcohol excess (consumption < 21 units/week) had borderline raised AST values. CONCLUSIONS: Statin-fibrate combination treatment for up to 3 years in a cohort of patients with coronary artery disease was not associated with serious disturbances in biochemical markers of muscle or liver function.
Angiotensin converting enzyme (ACE) genotypes have been associated with hypertension in the general population. However, the relation of ACE genotype to the prevalence of hypertension in diabetic populations is less clear. This study investigated ACE genotypes in 100 patients with diabetes mellitus, of whom 41 were on anti-hypertensive medication. A significant association was found between the presence of the ACE-D allele and hypertension in both the overall diabetic group (D = 0.66, P < 0.01) and in the subset of diabetics who had non-insulin-dependent diabetes (D = 0.69, P < 0.001). There was no correlation of ACE genotype with hypertension in insulin-dependent diabetes (D = 0.57).
In Caucasian subjects, elevated erythrocyte sodium-lithium countertransport (SLC) activity, displaying an increased affinity for external Na+ (decreased KNa), has a strong association with hypertension and has also been proposed as a potential marker for vascular disease. We have compared SLC activity and the kinetic components, KNa and maximal rate of turnover (Vmax), of the countertransporter in groups of Caucasian, Asian and Black hypertensive subjects matched for ethnicity, age and sex with healthy normotensive controls. SLC activity was the same in all ethnic groups irrespective of the presence of hypertension. Similarly, hypertension had no impact on Vmax values within each ethnic group (normotensive vs. hypertensives: Caucasian, 0.360 +/- 0.186 vs. 0.335 +/- 0.137; Asian, 0.324 +/- 0.078 vs. 0.273 +/- 0.105; black people, 0.192 +/- 0.123 vs. 0.178 +/- 0.082 mmol Li/l erythrocytes h). However, in black people compared with the other two ethnic groups, Vmax was lower for both controls and hypertensives (P < 0.05; ANOVA). Median KNa values in hypertensive subjects were consistently lower than their normotensive counterparts in all ethnic groups (P < 0.01; Kruskal-Wallis); Caucasians, (89.1 vs. 41.2 mmol Na; P = 0.01), Asians (121.1 vs. 33.1; P = 0.04) and black people (74.4 vs. 27.2 mmol Na; P = 0.02; Wilcoxon). The results show that Vmax is altered in black people independently of the presence of hypertension. This contrasts with KNa which, for each ethnic group studied, is reduced in the hypertensive compared with the normotensive state.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Familial hypercholesterolaemia (FH) is caused by mutations in the gene for the low density lipoprotein (LDL) receptor. It is generally believed that homozygous FH patients do not respond well to lipid-lowering drug therapy with inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase because they cannot respond to an increased demand for hepatic cholesterol by up-regulation of LDL-receptor activity. In this paper we show that serum cholesterol in a homozygous FH patient with a receptor-negative LDL-receptor phenotype was reduced by 30% after treatment with simvastatin alone and by a further 11% with simvastatin in combination with probucol and nicotinic acid. The patient was a true homozygote, with two identical alleles of the LDL receptor gene in which a previously undescribed point mutation in exon 11 introduces a premature termination codon at residue 540 in the protein; the mutant protein is predicted to be truncated in the domain with homology to the epidermal growth factor precursor. Cultured cells from the patient were unable to bind, internalise or degrade LDL by the receptor pathway and there was no immunodetectable LDL receptor protein in the cells. Thus the lipid lowering effect of simvastatin in this individual must involve mechanisms other than stimulation of LDL receptors.
A reduction in serum total alkaline phosphatase (ALP) activity is a well-documented side effect of treatment with bezafibrate and other fibric acid derivatives. To evaluate the effect of bezafibrate treatment on individual ALP isoenzyme activities, 10 patients were studied on two separate occasions, first, after a 6-week period on no drug treatment, and second, after 6 weeks of bezafibrate therapy. On each occasion, serum total ALP and ALP isoenzyme activities and serum gamma-glutamyltransferase (GGT) activity were measured both after fasting and following the ingestion of a standardized high-fat meal rich in long-chain fatty acid triglycerides, as intestinal ALP activity is known to be influenced by dietary fat intake. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured on fasting samples. In the fasting state, bezafibrate treatment resulted in a 25% reduction (P < .01) in serum total ALP activity; liver ALP activity was reduced by 40% (P < .01), and biliary ALP activity was reduced in those patients in whom it was initially detectable, while bone and intestinal ALP activities were unchanged. There was also a 15% reduction (P < .05) in serum GGT activity, but no change in plasma AST or ALT activities. Serum intestinal ALP activity increased significantly (P < .01) by 1 hour following ingestion of the high-fat meal, but treatment with bezafibrate did not change the magnitude of this response. There was no change in the activity of any other ALP isoenzyme following fat ingestion. This study demonstrates that the effect of bezafibrate on serum ALP activity is confined to the liver and biliary isoenzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
Intestinal alkaline phosphatase (IALP) activity rises following the ingestion of a fat-containing meal. Previous studies on intestinal fluid and lymph have shown that the magnitude of this response is dependent upon fatty acid chain length. To examine this relation in the serum of healthy humans, 10 subjects consumed two standardized fat meals. One meal contained predominantly long chain fatty acid triglycerides, the other contained predominantly medium chain fatty acid triglycerides. Serum IALP activity was measured in serial blood samples using a sensitive immunological assay. IALP activity was ABO blood group and secretor status dependent. The post-prandial rise in serum IALP activity was significantly greater following the long chain fatty acid meal than following the medium chain fatty acid meal. Previous observations of the fatty acid chain length dependency of the IALP response to fat ingestion, therefore, also apply in the serum of healthy humans under normal physiological conditions. Standardized fat meals provide the basis of a useful method for the investigation of the role of IALP in fat absorption.
The prevalence of hypercholesterolaemia and the frequency of a reduced HDL-cholesterol (at different cholesterol concentrations) were evaluated in a group of 400 diabetic patients attending a single diabetic clinic. Despite regularly supervised diabetes, including dietary advice, over one quarter of the patients had a serum total cholesterol concentration greater than 6.5 mmol/l, while over a quarter of the non-insulin treated and one eighth of the insulin treated diabetic subjects had an HDL-cholesterol less than 0.9 mmol/l, with a greater prevalence in the males compared with the females. More than 60% of all the diabetic patients who had a reduced HDL-cholesterol less than 0.9 mmol/l also had a total cholesterol concentration less than 6.5 mmol/l. When the total/HDL-cholesterol ratio was calculated more non-insulin treated subjects had a value greater than 4.5 as compared with insulin treated diabetic patients. When comparisons were made between an age matched group of diabetic patients (n = 185) and a group of non-diabetic subjects attending for a health screen (n = 155), the frequencies of serum cholesterol concentrations greater than 5.2, 6.5, and 7.8 mmol/l were similar for both groups. Significantly greater numbers of diabetic patients had a reduced HDL-cholesterol less than 0.9 mmol/l (at any level of serum cholesterol) and a total/HDL cholesterol ratio greater than 4.5. This study has shown that the measurement of serum total cholesterol concentration alone will not characterize many subjects who are at risk of macrovascular complications due to a reduced HDL-cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)
Cigarette smoking is known to affect many haematological parameters but little is known of their rate of return to normal on withdrawal of cigarettes. Two groups of chronic smokers were studied whilst smoking and in the 2 weeks after cessation. A rapid return towards normal was found in the elevated haemoglobin concentration, packed cell volume, red cell count, white cell count, neutrophil count, lymphocyte count and platelet count, indicating that at least some of the abnormalities in these parameters are an acute, reversible effect of cigarette smoking rather than being a response to tissue damage.
The incidence of cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM) has not been reduced by the control of hyperglycemia alone. Hypertension and dyslipidemia may be the major determinants of macrovascular disease in these patients. With the high prevalence of hypertension in NIDDM, antihypertensive drugs are likely to be important determinants of an atherogenic lipid profile. To date, there is no completed major randomized controlled trial of antihypertensive treatment outcome in a diabetic population, and as such, drug choice for the treatment of diabetic hypertension is often based on evidence extrapolated from studies in nondiabetic groups. However, two short-term studies have assessed the effects of doxazosin antihypertensive therapy in subjects with NIDDM. Both studies showed that the significant reduction in blood pressure with doxazosin treatment was associated with favorable effects on the serum lipid profile. In one study, contrasting adverse effects of atenolol treatment on glycemic control, lipids, and lipoproteins were observed. Doxazosin therapy was associated with a trend toward correcting the disturbances of lipoprotein metabolism characteristic of NIDDM. These metabolic effects, combined with effective lowering of blood pressure by doxazosin, may be important determinants of cardiovascular disease in the long term.
To evaluate how steroid trials are currently used in the assessment of reversibility of air flow limitation, a postal questionnaire was sent to 355 consultant members of the British Thoracic Society working in England and Wales; 253 questionnaires were returned (71% response rate). Two respondents did not undertake steroid trials; of the remaining 251, 75% prescribed 30-40 mg oral prednisolone, with the commonest treatment period being 2 weeks. A high dose steroid inhaler was sometimes used as an alternative by 31% of respondents. Although 71% of respondents made lung function measurements on several occasions before starting steroids and 76% made measurements during treatment, 78% assessed patients on only one occasion at the end of the trials to ascertain its outcome. Weight, blood pressure and glycosuria were measured less frequently after the steroid treatment compared to the pre-trial period. Blood glucose and serum electrolytes were infrequently measured both before and after treatment. Wide variations exist in steroid trial regimens and current practice may neither provide definitive evidence of treatment benefit nor an adequate safeguard for patients against potential side-effects.
Explore the source record for details and available documents.