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Biomedical subjects

C G Semple

Publications and source records attributed to C G Semple.

At least 19 recordsLinked to original sources

Psychological factors and their relationship to diabetes control.

Thirty-nine Type 1 diabetic patients were asked to complete an Eysenck Personality Questionnaire (EPQ). A significant relationship was found between neuroticism scores and glycosylated haemoglobin concentrations (r = 0.43, p < 0.01) and also fructosamine (r = 0.45, p < 0.01). Patients with glycosylated haemoglobin concentrations greater than or equal to 10 (n = 13) had significantly higher neuroticism scores than patients with glycosylated haemoglobin results less than or equal to 8 (n = 11) (p < 0.01).

Adolescent

Audit of multiple insulin injection regimens in a large outpatient diabetic population.

One hundred out-patients treated by multiple insulin injection regimens underwent clinical audit by retrospective analysis of their case-notes. Patients had been on multiple insulin injection therapy (MIIT) for 1.0-4.5 years (median, 3.6 years) and had had diabetes for 2 months-33 years (median, 8.7 years) at the time of starting pen therapy. Median daily insulin dose per patient did not differ significantly following stabilisation on MIIT or at latest follow-up. The median glycated haemoglobin did not change during each of the 4 years of follow-up. During the year prior to commencing MIIT the patients showed no significant alteration in body weight. Patients' weights rose significantly during each subsequent year. Median weight gains were 0.9 kg (P less than 0.005) during the first year, 1.4 kg (P less than 0.005) during the second year, 0.9 kg (P less than 0.05) during the third year and 1.4 kg (P less than 0.05) during year 4. No such weight gain was recorded in a control group of 30 patients matched for age and duration of diabetes and treated by twice daily insulin injections. Multiple insulin injection regimens used over prolonged periods in a routine clinic setting do not alter metabolic control. However, continuing weight gain appears to occur despite similar daily insulin doses.

Adolescent

An investigation of LH pulsatility in burned men by bioassay and radioimmunoassay.

LH pulsatility studies were performed in six burned patients by removing blood samples at 10 min intervals over a 6 h period. All samples were assayed for LH by bioassay (B-LH), LH by radioimmunoassay (I-LH) and testosterone. Mean serum testosterone concentrations of the burned patients were low (6.7 +/- 1.6 nmol/l). I-LH levels were lower than B-LH in all samples. Frequency of bioactive or immunoreactive pulses as well as mean B-LH and I-LH concentrations were similar to previously published data from normal men examined in the same laboratory. The mean biological activity of LH (expressed as the ratio of B-LH to I-LH, the B:I ratio) was lower in burned subjects (1.9 +/- 0.1) than previously reported in normal men. The B:I ratios of burned men were lower (p less than 0.01) at pulse peaks than at nadirs (1.8 +/- 0.1 vs 2.0 +/- 0.1) and an increase in serum testosterone concentration did not follow an LH peak. Serum testosterone concentrations did not cross-correlate with B-LH or I-LH. This contrasts with the findings in normal subjects where the B:I ratios have been found to be higher at pulse peaks than at nadirs and an increase in serum testosterone concentration follows a pulse peak and serum testosterone cross-correlates with B-LH and I-LH. LH secreted in a pulse peak in normal men may contain a particularly biologically potent form of the molecule but this may not be the case in burned men.

Adult

An assessment of the accuracy of NovoPen 1 delivery after prolonged use.

Forty-five NovoPen 1 injection devices have been assessed for accuracy of insulin delivery. Twenty-six pen-injectors had been returned either because the device had developed structural faults or the patients had experienced unexpected deterioration in diabetic control. Twelve of these pen-injectors were unusable. The remaining 14 pen-injectors ('faculty pen-injectors') were assessed by measuring the weight of insulin solution delivered in each of 10 depressions of the plunger and compared with similar measurements from 10 unused pen-injectors ('new pen-injectors') and 9 pen-injectors ('used pen-injectors') which had been used uneventfully for greater than 3 years. New pen-injectors delivered insulin solution with an accuracy (median error) of 2.8% and reproducibility (median SD) of 2.0%. Used pen-injectors had an accuracy of 2.3% and reproducibility of 3.5%. The 14 suspect pen-injectors ('faculty pen-injectors') demonstrated an accuracy of 2.8% with reproducibility of 4.0%. The reduction in reproducibility was due to faults in 4 pen-injectors, 2 of which consistently delivered less insulin than expected, while a further two pen-injectors were intermittently inaccurate.

Humans

An evaluation of human chorionic gonadotrophin (HCG) therapy in boys with delayed puberty.

Fifty male patients with delayed pubertal development (chronological age 13.3-17.6 years; bone age 9.5-14 years) were treated with human chorionic gonadotrophin (HCG) 1500-2000 units twice weekly for six months to promote pubertal development and accelerate growth. Response was compared with an untreated control group of 28 patients (chronological age 12.5-17.5 years; bone age 7.0-13.0 years). Forty-four of 46 patients in the treatment group achieved genital stage 3 or 4 by the end of therapy; untreated patients either remained unchanged or advanced only one genital stage during this period. Testicular volumes increased from a median 4.5 ml (range 1-12 ml) to 9 ml (range 3.5-15 ml) in the treated patients. In untreated patients testicular volume increased from 6.0 ml (range 2-10 ml) to 9.5 ml (range 4-20 ml) over the same period. In patients initially growing at less than 7.0 cm/year height velocity increased from 3.9 cm/year (range 0-6.6 cm/year) to 12.7 cm/year (range 8.9-16.8 cm/year) during therapy, falling to 6.0 cm/year (range 0-12 cm/year) in the three-month period immediately following treatment. Patients initially growing at greater than 7.0 cm/year showed variable responses to treatment. Prepubertal patients showed the greatest acceleration in annual growth compared with controls. Treated patients with an initial skeletal age less than 12.0 years showed either a final height (when known) which was less than initially predicted or a significant reduction in predicted height following treatment. Skeletal age greater than 12.0 years was not associated with excess osseous maturation. In conclusion, pre-pubertal children growing at less than 7 cm/year show the greatest benefit from HCG therapy, but final height may be prejudiced if initial bone age is less than 12 years.

Adolescent

Endocrine effects of examination stress.

1. We have studied endocrine function in nine healthy young men 16 weeks before and immediately after Final degree examinations. Factors other than psychological stress which might have affected hormone levels were excluded. 2. The presence of psychological stress at the time of examinations was confirmed by finding increased values for two self-rating anxiety scales. 3. Urine metadrenaline excretion was increased in all subjects at the time of examination. Serum and early morning urine cortisol as well as pituitary-testicular and pituitary-thyroid function and prolactin levels were unaffected by examination stress. 4. This study questions the popular belief that psychological stress stimulates prolactin secretion and suppresses pituitary-testicular function.

Adult

Androgen levels in men with diabetes mellitus.

Patients in varying degrees of diabetic ketoacidosis had low serum testosterone levels which rose following recovery (5.4 +/- 1.3----13.7 +/- 1.7 nmol/l, p less than 0.02, mean +/- SE). Blood glucose control of 30 non-ketotic diabetic men (15 insulin-dependent and 15 non-insulin-dependent) did not correlate significantly with serum testosterone concentrations. Although previous authors had suggested that the adrenal androgen status of diabetic patients might be abnormal, adrenal androgens androstenedione and dehydroepiandrosterone sulphate (DHEAS) were similar in our 30 men to age-matched healthy men.

Androgens

Inhibition of glucose-induced insulin secretion by calcium channel blocking drugs in-vitro but not in-vivo in the rat.

The organic calcium channel blocking drugs darodipine, nicardipine, diltiazem and verapamil inhibited glucose-induced (8.3 mmol L-1) insulin secretion by rat isolated islets in a concentration-dependent manner. The IC50 values (mumol L-1) for nicardipine, diltiazem and verapamil were 0.0025, 1.94 and 3.6, respectively. There were no significant differences between the potencies of any one drug when compared at two different glucose concentrations (27.8 and 8.3 mmol L-1). Isolated islets were also responsive to the calcium channel activating drugs BAY K 8644 and CGP 28392, which enhanced glucose-induced insulin secretion and prevented the inhibitory effect of verapamil. BAY K 8644 was more potent than CGP 28392. In the anaesthetized rat, neither verapamil (1 mg kg-1 i.v. 10 min before glucose) nor nicardipine (0.2 mg kg-1 i.v.) modified the glucose or insulin response to intravenous glucose whilst producing marked cardiovascular effects. The plasma concentrations of nicardipine (3.9 X 10(-8) M at 10 min post injection) were similar to those producing effects in-vitro whereas the plasma concentrations of verapamil (5 X 10(-7) M) were lower. It thus appears that the islet B cell calcium channel is less sensitive to calcium channel blocking drugs in-vivo than in-vitro. Moreover, in-vivo, the cardiovascular system is more sensitive to these drugs than are the islet B cells, although the potencies of the calcium channel blocking drug in isolated islets are similar to those reported for cardiac muscle and vascular smooth muscle in-vitro.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Mechanisms leading to hypogonadism in men with burns injuries.

A profound and persistent depression of serum testosterone concentrations was found in 19 men with burns injuries. This could not be explained by changes in sex hormone binding globulin capacity, hyperprolactinaemia, classical primary testicular failure, or a hypogonadotrophic state. Pulsatile release of luteinising hormone was found in control subjects but was absent or diminished in burnt patients with low serum testosterone concentrations. In addition, these patients showed reduced biological activity of luteinising hormone as measured by bioassay even though normal concentrations of luteinising hormone were detected by radioimmunoassay. The temporary hypogonadism after burns injury and possibly in other clinical states may be related to hypothalamic dysfunction, which leads to abnormal generation of luteinising hormone releasing hormone and non-pulsatile secretion of luteinising hormone of reduced biological activity.

Adult

Can thyroid stimulating hormone levels by TSH (IRMA) predict relapse of thyrotoxicosis following carbimazole treatment?

Serum thyrotrophin receptor antibody (TRAb) and thyroid stimulating hormone (TSH) (IRMA) levels were measured in 38 patients at one month after the end of a course of carbimazole/T3 therapy for Graves' disease. Despite the increased sensitivity of the IRMA assay a TSH measurement at this stage was found to be of no predictive value, in contrast to estimation of serum TRAb levels which correctly predicted relapse and remission in 90% of patients.

Autoantibodies

A study of hypothalamic-pituitary-adrenal suppression following curative surgery for Cushing's syndrome due to adrenal adenoma.

The hypothalamic-pituitary-adrenal axis was investigated in all six patients requiring glucocorticoid replacement 2.5-11 years after unilateral adrenalectomy for adrenal adenomas causing Cushing's syndrome. The hypothalamic-pituitary-adrenal axis was assessed by insulin induced hypoglycaemia and CRF testing in each patient. Two patients showed normal cortisol and ACTH responses to hypoglycaemia. Two patients showed subnormal cortisol responses to hypoglycaemia in the presence of high or normal basal ACTH concentrations. ACTH concentrations increased with both hypoglycaemia and CRF. Two patients showed subnormal cortisol responses to hypoglycaemia and CRF. One of these patients showed an ACTH rise following hypoglycaemia but not CRF. Defects at either hypothalamic-pituitary or adrenal levels were demonstrated and recovery of the axis appears to commence at the hypothalamic-pituitary level.

Adenoma

Adrenal androgens and illness.

We have studied the adrenal androgen status of medically ill patients, patients before and after cholecystectomy and during recovery from burns injury. In patients ill for less than 2 weeks, serum androstenedione concentrations (mean +/- SEM) were raised (7.94 +/- 0.98 nmol/l) as compared with a control group (4.83 +/- 0.38 nmol/l, P less than 0.005) or with patients ill for more than 2 weeks (5.21 +/- 0.46 nmol/l, P less than 0.02); serum dehydroepiandrosterone sulphate (DHAS) levels were lower in patients ill for more than 2 weeks (1.21 +/- 0.42 mumol/l) than in either the acutely ill group (5.98 +/- 1.06 mumol/l, P less than 0.001) or the control ill group (5.56 +/- 0.59 mumol/l, P less than 0.001). In post-operative patients serum DHAS levels fell to below pre-operative levels reaching a nadir at day 8 (0.54 +/- 0.19 vs 1.66 +/- 0.56 mumol/l, P less than 0.02). In burned patients serum cortisol levels were increased on admission (661 +/- 91 vs 359 +/- 30 nmol/l, P less than 0.005) and remained high over the study period. Serum androstenedione concentrations were also high on admission (7.5 +/- 1.0 vs 3.9 +/- 0.3 nmol/l, P less than 0.02). Serum DHAS concentrations were similar to control values on admission (6.8 +/- 1.2 vs 5.2 +/- 0.7 mumol/l), fell to low levels thereafter reaching a nadir during week 3 (1.6 +/- 0.6 mumol/l, P less than 0.001). Steroid synthesis in times of chronic illness may be diverted from adrenal androgen to corticosteroid pathways ensuring maintained secretion of cortisol, which is essential to the health of ill patients.

Adrenal Cortex

Male hypogonadism--a non-specific consequence of illness.

Depressed thyroid hormone levels are commonly found in sick patients. Low serum testosterone concentrations have also been described in men suffering from a number of illnesses. To investigate whether this might be a non-specific marker of illness, various endocrine parameters were measured in 30 male patients in a general medical ward. Patients were suffering from a wide spectrum of medical disorders and were not receiving drugs known to affect endocrine function. Results were compared with a healthy age-matched control group. Serum testosterone concentrations (mean +/- SE) were low in the patient group (8.9 +/- 1.1 vs. 18.2 +/- 1.4 nmol/l, p less than 0.001), correlated significantly with serum T3 levels but were not related to prognosis. Half the patients had testosterone levels below the normal control range. Changes in testosterone concentrations could not be explained on the basis of binding protein changes, hyperprolactinaemia or depressed pituitary secretion of gonadotrophins. Depression of serum testosterone concentrations is a non-specific marker of illness.

Adolescent

Effect of oral verapamil on glibenclamide stimulated insulin secretion.

In order to study the effect of the calcium antagonist, verapamil, on glibenclamide stimulated insulin release, nine healthy fasted male volunteers were given 5 mg oral glibenclamide with either 120 mg oral verapamil or placebo in a double-blind crossover manner 1 week apart. Blood was withdrawn at intervals for drug, hormonal and glucose estimations. Concomitant administration of verapamil resulted in higher levels of glibenclamide at each time point (P less than 0.01) suggesting that verapamil interferes with glibenclamide metabolism. However, levels of plasma glucose, C-peptide, insulin and glucagon did not differ between the verapamil and placebo studies.

Adult

Addison's disease without pigmentation.

Four cases of Addison's disease are described in whom the diagnosis was unexpected or dangerously delayed because of the absence of pigmentation.

Addison Disease

Cushing's syndrome and autonomous thyroid nodules, a variant of multiple endocrine neoplasia?

Over a 20 year period 4 of 40 (10%) female patients with Cushing' syndrome also had a solitary thyroid nodule. In 3 cases this was an autonomous 'hot' nodule. In the same population only one case of presumed Graves' disease was seen. It is postulated that the association of autonomous thyroid nodule and Cushing's syndrome may represent a variant of multiple endocrine neoplasia.

Adenoma