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Biomedical subjects

D M Large

Publications and source records attributed to D M Large.

At least 19 recordsLinked to original sources
PubMed1992

Blisters, ulceration and autonomic neuropathy in carpal tunnel syndrome.

We describe three patients with trophic ulceration and blistering of the fingertips associated with carpal tunnel syndrome. One of the patients also had non-insulin-dependent diabetes mellitus. Autonomic neuropathy distal to the carpal tunnel was probably present in all subjects at the time of presentation; in the patient with recent symptoms the skin was warm, and sweating was virtually absent, whilst the other two patients described cold skin, consistent with prolonged autonomic neuropathy.

Aged↗
PubMed1991

Intravenous gammaglobulin therapy in the thrombocytopenia of haemorrhagic varicella.

We report the case of a teenage boy with thrombocytopenia complicating varicella infection, which responded promptly to treatment with intravenous immunoglobulin therapy. Such treatment is well recognized in the management of immune thrombocytopenia, particularly where steroids are contra-indicated, but we have not found any previous case reports of the use of immunoglobulin in this condition.

Adolescent↗
PubMed1985

Short-term effects of beta-adrenoceptor blocking drugs with and without cardioselectivity and intrinsic sympathomimetic activity on lipoprotein metabolism in hypertriglyceridaemic patients and in normal men.

In six patients with hypertriglyceridaemia presenting whilst receiving treatment with beta-adrenoreceptor blocking drugs (mean serum triglycerides 31.2 mmol/l) the half-life (t1/2) of an intravenously administered triglyceride emulsion was 32.8 +/- 7.9 min (mean +/- SEM) on beta-blocker and 22.8 +/- 4.8 min after stopping beta-blocker treatment. In three of these patients subsequent administration of a beta-blocker with intrinsic sympathomimetic activity had no effect on t1/2. In a cross-over trial of placebo, atenolol (beta 1-blocker), propranolol (beta 1- and beta 2-blocker) and pindolol (beta 1- and beta 2-blocker with intrinsic sympathomimetic activity) in 11 normal men t1/2 was 11.8 +/- 0.9, 12.6 +/- 1.1, 14.3 +/- 1.7 and 12.4 +/- 1.1 min respectively. None of the apparent differences achieved statistical significance, but in two men marked increases in t1/2 occurred on propranolol. The concentrations of serum triglycerides and very low density lipoprotein cholesterol in the normal men were, however, increased by beta-blockade, most markedly by pindolol. Serum high density lipoprotein (HDL) cholesterol concentration decreased in normal men on beta-blockers, most clearly on atenolol and propranolol. This decrease was due to a reduction in cholesterol in the HDL2 subfraction. No statistically significant effects on serum low density lipoprotein cholesterol or apolipoprotein B concentrations occurred in the normal men. The doses of atenolol and propranolol used in this study were equipotent as judged by the heart rate response to exercise.

Adrenergic beta-Antagonists↗
PubMed1985

Evidence that adrenal oestrogens are not involved in benign breast disease.

We have studied 30 women with symptomatic benign breast disease in order to test the hypothesis that in some it might be caused by an enzyme variant leading to excessive adrenal production of oestrone. Synthetic 1-24 ACTH (Synacthen) was given intramuscularly after overnight suppression with dexamethasone, during the early follicular phase of the menstrual cycle. In no subjects did plasma oestrone levels show a consistent and significant response to ACTH despite the expected consistent rises in androstenedione and cortisol. We conclude that it is unlikely that adrenal oestrogens play a significant role in the pathophysiology of even a minority of patients with benign breast disease.

Adult↗
PubMed1984

Dystrophic calcification, cataracts, and enamel hypoplasia due to long-standing, privational vitamin D deficiency.

A 19-year-old Indian girl presenting with intermittent tetany, enamel hypoplasia, bilateral cataracts, and calcification of the basal ganglia is described. Dental evidence suggested a calcification defect had been present from the age of 2-3 years. Hypocalcemia, hyperphosphatemia, and low levels of immunoassayable parathyroid hormone (iPTH), urinary cAMP, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were documented, suggesting hypoparathyroidism with vitamin D deficiency. A bone biopsy showed osteomalacia. Following ultraviolet irradiation and oral calciferol therapy, a symptomatic and biochemical response typical of privational vitamin D deficiency occurred. iPTH levels rose to normal and remained normal following withdrawal of treatment, indicating that the clinical features were entirely due to long-standing vitamin D deficiency.

Adult↗
PubMed1984

Gorlin's syndrome with a cardiac lesion and jaw cysts with some unusual histological features. A case report and review of the literature.

A 25-year-old male with Gorlin's syndrome associated with an intracardiac lesion, presented with jaw cysts requiring surgical treatment. One of the cysts contained unusual histological components including fibrous tissue, myxomatous stroma and abnormal epithelial hyperplasia. Metabolic investigation showed normal parathyroid function and normal tissue responsiveness to parathyroid hormone, despite several clinical and radiological features suggestive of pseudo-hypoparathyroidism. The principal features of the syndrome are reviewed.

Adult↗
PubMed1984

A simple test for the hormonal assessment of early puberty in boys.

The initial hormonal changes in male puberty occur at nighttime, with episodic rises of LH and testosterone (T). Only much later do the daytime levels of these hormones rise. Nocturnal sampling is impractical for routine clinical assessment, so we have examined the relationship between peak nocturnal T levels and those produced in the same subject by a single intravenous injection of gonadotrophin releasing hormone (GnRH, 100 micrograms) in the morning. Nocturnal T profiles and daytime GnRH tests have been conducted in eight boys in early (delayed) puberty, three with pubertal gynaecomastia in later puberty, two normal men, and one man with gynaecomastia. Excellent agreement was obtained between peak nocturnal and post-GnRH T levels. The serum testosterone level 3 hours after 100 micrograms IV GnRH is a simple and useful hormonal marker of pituitary-Leydig cell activity during puberty.

Adolescent↗
PubMed1984

Which testosterone replacement therapy?

Three different forms of testosterone (T) replacement therapy were compared; they were the intramuscular injection of mixed testosterone esters 250 mg; the subcutaneous implantation of 6 X 100 mg pellets of fused testosterone; and the oral administration of testosterone undecanoate (TU) 80 mg twice daily. Six hypogonadal males were treated with oral TU for an eight week period, during which time serial serum hormonal estimations were performed over 10 h at the initiation and after four and eight weeks of therapy. Serum T levels showed marked variability both between subjects and within the same subject on different occasions. We attribute this to variability in absorption of TU, which is formulated in oleic acid. The overall mean T level calculated from the areas under the profiles of TU was 12.0 nmol/l. Hormone responses to injected T esters were studied in nine hypogonadal males. Serum T rose to supraphysiological peak concentrations (mean 71 nmol/l) 24-48 h after an injection, followed by an exponential decay to reach baseline concentrations after 2-3 weeks. The overall calculated mean T level in subjects receiving testosterone esters 250 mg every three weeks was 27.7 nmol/l. Subcutaneous implantation of testosterone in six hypogonadal men produced a gradual rise in serum T followed by a slow decline, with T levels remaining within the normal range for 4-5 months. The calculated overall mean T level over 21 weeks after implantation was 17.0 nmol/l. Serum oestradiol (E2) levels remained within the normal male range throughout the study periods on both TU and T implant therapy but showed a supraphysiological peak (mean 347 pmol/l) 24-48 h after a T injection. 5 alpha-dihydrotestosterone (DHT) levels appeared to parallel those of T on the three forms of therapy, with DHT:T ratios being highest for TU therapy. This was also true for the target organ metabolite 5 alpha-androstane-3 alpha,17 beta-diol. At the doses studied drug costs were similar for T implantation (every 5 months) and T ester injections (every 3 weeks), but were 7-8 times higher for TU (80 mg twice a day). We conclude that T implantation remains overall the most physiological form of androgen replacement therapy, is generally well accepted and attended by few side effects; TU may have a useful role in the initial phases of therapy.

Administration, Oral↗
PubMed1984

Hyperkalaemia in diabetes mellitus--potential hazards of coexisting hyporeninaemic hypoaldosteronism.

Two patients with insulin-dependent diabetes mellitus (Type I), developed severe, life-threatening hyperkalaemia, the first following treatment with spironolactone, the second during treatment for staphylococcal septicaemia when glucose-induced hyperkalaemia occurred. Investigations demonstrated co-existing hyporeininaemic hypoaldosteronism. Prompt recognition of this combined hormone-deficiency syndrome led to appropriate treatment and recovery. The biochemical features and clinical importance of hyporeninaemic hypoaldosteronism are discussed.

Adult↗
PubMed1984

High dose androgen therapy in male pseudohermaphroditism due to 5 alpha-reductase deficiency and disorders of the androgen receptor.

We describe the clinical and biochemical features of six men with male pseudohermaphroditism due to androgen resistance. Each of the subjects had male-gender behavior but incomplete virilization. The underlying defects in androgen metabolism were defined by studies of the 5 alpha-reductase enzyme and the androgen receptor in fibroblasts cultured from biopsies of genital skin. Four of the six have 5 alpha-reductase deficiency, and two have defects of the androgen receptor (the Reifenstein syndrome). The responses of these men to androgen treatment were assessed by monitoring nitrogen balance, plasma luteinizing hormone (LH) values, and clinical parameters of virilization including penile growth, potency and ejaculatory volume, muscle bulk, and growth of body and facial hair. In all of the subjects with 5 alpha-reductase deficiency and one man with the Reifenstein syndrome significant response occurred, as evidence by nitrogen retention, lowered plasma LH levels, and improved virilization, with doses of parenteral testosterone esters that raised plasma testosterone levels above the normal male range and brought plasma dihydrotestosterone levels into the normal male range. The subject who did not respond with clinical virilization nevertheless showed nitrogen retention in response to acute testosterone administration. This patient had a profound deficiency of the androgen receptor, whereas the man with a receptor defect who did respond clinically to therapy had normal amounts of a qualitatively abnormal receptor. We conclude that high dose androgen therapy may be of benefit in improving virilization, self-image, and sexual performance in subjects with 5 alpha-reductase deficiency who have male-gender behavior and in some subjects with defects of the androgen receptor.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1983

Basal steroid production by the zona reticularis of the guinea-pig adrenal cortex.

The zonae glomerulosa and fasciculata (ZG/ZF) have been separated by microdissection from the zona reticularis (ZR) of the guinea-pig adrenal cortex. Using non-proliferative organ culture and specific radioimmunoassay the basal secretion of 12 steroids from each zone have been studied. The ZG/ZF secreted 9 times more cortisol (in pmol/mg dry weight 5 h culture) than the ZR. In contrast the androgens (androstenedione, 5-androstenediol, dehydroepiandrosterone, dehydroepiandrosterone-sulphate and testosterone) were preferentially produced (by a factor of 3) by the ZR which also secreted more of all the other steroids studied, with the exception of progesterone and 17-hydroxyprogesterone. The mean molar ratios of total androgen output to cortisol secretion were 1:1.7 and 1:45 for the ZR and ZF respectively. Using computerised image analysis the relative volumes of the ZG/ZF and ZR in the cortex were calculated to be 65 and 35% respectively. The medulla occupies 4.6% of the total gland. From the zonal composition of the cortex, the relationship between wet and dry weight for each zone and the basal secretion rate of each steroid/mg dry weight/5 h culture, we calculated that the ZR could be responsible for 7 and 66% of the cortisol and total androgen secretion respectively from the guinea-pig adrenal gland. It is concluded that the ZF and ZR are functionally as well as morphologically distinct.

Adrenal Cortex↗
PubMed1983

Gynaecomastia complicating the treatment of myeloma.

The hormonal mechanisms involved in the development of gynaecomastia accompanying the treatment of multiple myeloma in adult men have been investigated by studying levels of circulating testosterone (T), oestrone (EI), oestradiol (E2), sex-hormone binding globulin (SHBG), prolactin (PRL) and the gonadotrophins LH and FSH, before, during and after development of gynaecomastia in 4 men. These have been compared with 5 closely matched men who did not develop gynaecomastia during similar treatment for myeloma. Levels of circulating T fell, and levels of E1 and E2 rose during treatment periods in all subjects, and the changes were statistically significant in subjects developing gynaecomastia, which resolved as levels of sex steroid returned towards normal following cessation of treatment. We conclude that treatment of adult men for myeloma results in testicular dysfunction with a reduction in circulating T and a rise in circulating oestrogens. These changes are most marked in subjects developing gynaecomastia in whom the normal breast tissue is stimulated by a subtle, transient oestrogen:androgen imbalance in favour of oestrogens.

Aged↗