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M J Diver

Publications and source records attributed to M J Diver.

At least 19 recordsLinked to original sources
PubMed2000

Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Experimental studies suggest that androgens induce coronary vasodilatation. We performed this pilot project to examine the clinical effects of long-term low-dose androgens in men with angina. METHODS AND RESULTS: Forty-six men with stable angina completed a 2-week, single-blind placebo run-in, followed by double-blind randomization to 5 mg testosterone daily by transdermal patch or matching placebo for 12 weeks, in addition to their current medication. Time to 1-mm ST-segment depression on treadmill exercise testing and hormone levels were measured and quality of life was assessed by SF-36 at baseline and after 4 and 12 weeks of treatment. Active treatment resulted in a 2-fold increase in androgen levels and an increase in time to 1-mm ST-segment depression from (mean+/-SEM) 309+/-27 seconds at baseline to 343+/-26 seconds after 4 weeks and to 361+/-22 seconds after 12 weeks. This change was statistically significant compared with that seen in the placebo group (from 266+/-25 seconds at baseline to 284+/-23 seconds after 4 weeks and to 292+/-24 seconds after 12 weeks; P:=0.02 between the 2 groups by ANCOVA). The magnitude of the response was greater in those with lower baseline levels of bioavailable testosterone (r=-0. 455, P:<0.05). There were no significant changes in prostate specific antigen, hemoglobin, lipids, or coagulation profiles during the study. There were significant improvements in pain perception (P:=0.026) and role limitation resulting from physical problems (P:=0.024) in the testosterone-treated group. CONCLUSIONS: Low-dose supplemental testosterone treatment in men with chronic stable angina reduces exercise-induced myocardial ischemia.

Administration, Cutaneous↗
PubMed2000

Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms.

AIMS: High androgen levels are presumed by many to explain the male predisposition to coronary artery disease. However, natural androgens inhibit male atherosclerosis(1). Our aim was to determine whether levels of androgens differ between men with and without coronary artery disease. METHODS AND RESULTS: Ninety male subjects (60 with positive, and 30 with negative coronary angiograms) were recruited. Early morning, fasting blood samples were taken from each patient and free, total and bioavailable testosterone, sex hormone binding globulin, oestradiol, and lipids were measured. Bioavailable testosterone was assayed using a modified technique. Free androgen index was calculated. Men with coronary artery disease had significantly lower levels of free testosterone (mean (standard deviation)); 47.95 (13.77) vs 59.87 (26. 05) pmol. l(-1), P=0.027), bioavailable testosterone; 2.55 (0.77) vs 3.26 (1.18) nmol. l(-1), P=0.005 and free androgen index; 37.8 (10. 4) vs 48.47 (18.3), P=0.005, than controls. After controlling for differences in age and body mass index the differences in free androgen index and bioavailable testosterone remained statistically significant (P=0.008 and P=0.013, respectively). CONCLUSION: Men with coronary artery disease have significantly lower levels of androgens than normal controls, challenging the preconception that physiologically high levels of androgens in men account for their increased relative risk for coronary artery disease.

Adult↗
PubMed1999

Angiotensin II concentrations and gut mucosal perfusion in infants undergoing cardiopulmonary bypass.

OBJECTIVES: To determine whether hypothermic cardiopulmonary bypass (CPB) per se causes an increase in angiotensin II (A-II) concentration in infants and to investigate the relationship between A-II concentration and gut mucosal perfusion. DESIGN: Prospective, open, nonrandomized, observational study. SETTING: Children's teaching hospital. PARTICIPANTS: Thirty acyanotic infants requiring CPB. INTERVENTIONS: A-II concentrations were measured on six occasions before, during, and after CPB. An orogastric tonometer allowed intermittent calculations of gastric intramucosal pH (pHi). Gastric mucosal blood flow (flux) was monitored using a laser Doppler flowmeter. Ten infants acted as controls (group 1); 10 infants received captopril, 0.9 mg/kg orally, 45 minutes before induction of anesthesia (group 2), and 10 infants received enalaprilat, 0.06 mg/kg intravenously, just before CPB (group 3). MEASUREMENTS AND MAIN RESULTS: A-II concentrations were abnormally high in 28 of 30 patients before CPB (median, 450 pg/mL (range, 83 to 5,787 pg/mL). A-II concentrations in groups 1 and 2 decreased during CPB, but values remained at twice normal levels throughout surgery (median, 171 to 198 pg/mL post-CPB). A-II concentrations remained normal (range, 52 to 120 pg/mL) during and after CPB in patients receiving enalaprilat (group 3). The authors found no significant correlation between A-II concentration and pHi or flux before, during, or after surgery. CONCLUSIONS: Acyanotic infants requiring cardiac surgery may have high perioperative concentrations of A-II. Hypothermic CPB is associated with a decrease in A-II concentration. Reductions in gut mucosal perfusion seen in some infants during hypothermic CPB are not related to increases in A-II concentrations.

Angiotensin II↗
PubMed1999

Admission cortisol and adrenocorticotrophic hormone levels in children with meningococcal disease: evidence of adrenal insufficiency?

OBJECTIVE: To measure admission cortisol and adrenocorticotrophic hormone (ACTH) levels in children with meningococcal disease to try and determine the prevalence of adrenal insufficiency. DESIGN: Prospective observational study. SETTING: Pediatric departments of four hospitals in Merseyside, United Kingdom. PATIENTS: Ninety-six children with meningococcal disease; 29 with hypotension, ten of whom died. MEASUREMENTS AND MAIN RESULTS: Admission cortisol, ACTH, and proinflammatory cytokine levels were measured. Serial cortisol levels also were measured during the first 48 hrs. Significantly lower cortisol levels were found in those who died compared with survivors. Significantly higher ACTH levels also were found in those who died. However, no child had a cortisol level <5 microg/dL (<138 nmol/L) implying definite adrenal insufficiency. Three of 29 children with hypotension had plasma cortisol levels implying possible adrenal insufficiency (<18 microg/dL [<497 nmol/L]), but high ACTH levels were only found in one of those three. Cortisol levels decreased significantly after antibiotic treatment, unless steroid therapy was administered. ACTH levels did not correlate with cortisol or proinflammatory cytokine levels. CONCLUSIONS: Children with meningococcal disease have a wide range of initial plasma cortisol levels, with lower levels found in those who die. Many factors may affect cortisol levels, but adrenal insufficiency is probably uncommon.

Adolescent↗
PubMed1996

Undiagnosed morbidity in adult women with Turner's syndrome.

OBJECTIVE: Adult patients with Turner's syndrome are rarely followed up at specialist clinics after discharge from paediatric care but do have a predisposition to several long-term medical problems. We have assessed the undiagnosed morbidity that exists among adult women with Turner's syndrome. PATIENTS: A group of 32 women (age range 17-52 years; mean 25 years) attending a specialist out-patient clinic. MEASUREMENTS: Blood samples were obtained at the initial visit for lipid assessment, thyroid function, gonadal status and routine biochemical profile. Bone mineral density (BMD) was measured in 31 of the women. RESULTS: Thirty-one women were receiving some form of oestrogen replacement. Two were receiving T4 therapy. In 50%, total cholesterol was greater than 5.2 mmol/l (range 3.4-9.3 mmol/l, mean 5.8 mmol/l) and 28% had an abnormality of thyroid function tests. Two women were newly diagnosed as hypothyroid, 6 had compensated hypothyroidism and one was under-replaced with T4. Lumbar spine BMD was below 100% of age matched reference range in 84% and below 75% in 26% of patients. Femoral neck BMD was below 100% of age matched reference range in 90% and below 75% in 10% of patients. CONCLUSIONS: There is a high incidence of undiagnosed lipid, thyroid and bone mineral density abnormalities in the adult population with Turner's syndrome. Doctors caring for these women need to be aware of and look for the potential problems. Appropriate long-term treatment should be commenced to help prevent the development of lipid, skeletal and thyroid abnormalities which may cause these patients major problems in the future.

Adolescent↗
PubMed1995

Exaggerated effects of progestogen on uterine artery pulsatility index in Turner's syndrome patients receiving hormone replacement therapy.

OBJECTIVE: To investigate the effect of estrogen and progestogen on the resistance to blood flow in the uterine arteries of Turner's syndrome patients. DESIGN: Prospective clinical study. SETTING: A tertiary infertility clinic. PATIENTS: Five Turner's syndrome patients, six patients who had surgical castration, and five patients with idiopathic primary ovarian failure. INTERVENTIONS: The patients were treated with 2 mg E2 valerate to which 500 micrograms norgesterel was added for 10 days in a 28-day cycle. Transvaginal color Doppler was used to measure pulsatility index in the uterine arteries at eight regular intervals during a single cycle. MAIN OUTCOME MEASURE: Pulsatility index of the uterine arteries. RESULTS: The administration of norgesterel to Turner's syndrome patients resulted in an increase in pulsatility index that was significantly higher than in patients who had surgical castration (confidence interval = 0.17 to 2.42). CONCLUSION: The uterine arteries of Turner's syndrome patients are more sensitive to the tonic effect of progestogen. If manifest in cardiac arteries also this phenomenon may be partly responsible for the increased incidence of cardiovascular disease and shorter life expectancy in Turner's syndrome patients. To achieve optimal protection from cardiovascular disease, Turner's syndrome patients may benefit from hormone replacement treatment containing altered doses of estrogen and progestogen.

Arteries↗
PubMed1994

The long-term stability in whole blood of 14 commonly-requested hormone analytes.

Concentrations of 14 commonly-requested plasma hormones were measured in octuplicate in each of six subjects to determine their stability when unseparated from red cells for periods up to 1 week. Most of the analytes were stable when stored in this way and although statistically significant changes were recorded, in the great majority of cases the changes seen would have no bearing on the clinical interpretation of the result. In the light of these findings, we would confidently report results of analyses for these hormones in plasma that had remained in contact with red cells at ambient temperature for long periods of time.

17-alpha-Hydroxyprogesterone↗
PubMed1993

The effect of free fatty acids on the in-vitro binding of testosterone in human plasma.

The effect of supraphysiological levels of free fatty acids (FFA) on the binding of testosterone to sex-hormone binding globulin (SHBG) and on non-SHBG binding in both male plasma and plasma from pregnant women was studied. Six FFAs were added to plasma as individual acids. No alteration in testosterone binding to SHBG could be demonstrated with any of the FFAs in either male plasma or plasma from pregnant women. When the same plasma was heated to destroy SHBG binding, a highly significant (P < 0.01) increase in non-SHBG binding was seen in both male plasma and plasma from pregnant women when the unsaturated FFAs oleic, linoleic and linolenic acids were added. No significant difference was demonstrated with the saturated FFAs, palmitic, stearic and arachidic acids.

Fatty Acids, Nonesterified↗
PubMed1991

Autoimmune Addison's disease and thyrotoxic thyroiditis presenting as encephalopathy in twins.

An 11 year old boy who presented with neuropsychiatric symptoms including delirium and pronounced agitation was found to have simultaneous onset of autoimmune adrenocortical insufficiency and hyperthyroidism. His identical twin also had hyperthyroidism and six months later developed symptoms of adrenocortical insufficiency. In children presenting with neuropsychiatric symptoms, adrenal (or pituitary) and other endocrine disorders should be considered.

Addison Disease↗
PubMed1989

Plasma aldosterone and renin activity.

Eight infants had paired measurements of plasma aldosterone and plasma renin activity while being treated for congestive heart failure. There is parallelism with aldosterone and renin activity in the presence of a hyperactive renin-angiotensin-aldosterone system. Six patients had plasma renin activity and plasma aldosterone measured after commencing captopril and we have shown biochemical blockade of the renin-angiotensin-aldosterone system.

Aldosterone↗
PubMed1988

Virilization due to ovarian hyperthecosis in a postmenopausal woman.

A 51-year-old woman presented with hirsutism and virilization of gradual onset. The serum gonadotropin concentrations were in the postmenopausal range, the serum testosterone concentration was markedly elevated (9.8 nmol/l) and the serum estradiol concentration (220 pmol/l) was elevated above the postmenopausal range. A selective venous catheterization study demonstrated raised serum testosterone and androstenedione levels in ovarian veins and suggested the presence of a left ovarian tumor. The raised peripheral estradiol level was shown to be due to ovarian hypersecretion. After bilateral oophorectomy the serum testosterone became normal. Ovarian histology revealed bilateral stromal hyperthecosis. Ovarian hyperthecosis is a rare but important cause of serum testosterone levels in the neoplastic range. This is the third case reported of postmenopausal virilization due to ovarian hyperthecosis and the first report of a selective venous catheterization study in such a patient.

Androstenedione↗
PubMed1987

Plasma progesterone concentration in women with and without adenocarcinoma of the endometrium.

In the search for the postulated but elusive "estrogenic bias" in patients developing endometrial cancer, several authors have suggested lack of progesterone as the common denominator. In this study 21 patients at the time of diagnosis of Stage I disease are compared to stringently matched healthy control subjects. No significant difference was found in plasma progesterone concentrations between the two groups. These results, in conjunction with other calculated estrogenic indices based on these patients, provide no evidence of lack of progesterone at the onset of clinical disease. However, the effects of long-term progesterone lack related to chronic anovulation are not excluded by these findings.

Adenocarcinoma↗