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Plasma dexamethasone concentrations following oral dexamethasone administration were examined in 78 patients with major depression prior to and during treatment. The test-retest stability of plasma dexamethasone levels within patients was satisfactory with an overall significant positive correlation between tests for each patient. However, significant variability was noted in individual patients. Change in pre-DST cortisol and plasma dexamethasone levels were the two variables, in that order of importance, contributing to change in DST status. In studies examining the clinical utility of serial dexamethasone suppression tests as a guide to recovery from depression, the effect of variability in plasma dexamethasone concentrations should be taken into account.

The uptake of 2-[1-14C]deoxyglucose in vivo by brown adipose tissue was greater than that of brain or heart in control mice on a whole tissue basis. When mice were treated with noradrenaline the rate of uptake of 2-[1-14C]deoxyglucose by brown adipose tissue was increased 6-fold with the only other change occurring in heart where a 5-fold increase was observed. After administration of insulin the uptake of 2-[1-14C]deoxyglucose in vivo was increased in heart, brown adipose tissue, white adipose tissue and muscle. The amount of 2-[1-14C]deoxyglucose taken up by brown adipose tissue compared to other tissues and the changes in this uptake after administration of noradrenaline or insulin suggest that brown adipose tissue is capable of playing a quantitatively important role in glucose removal from the blood.

Testicular function was assessed in 24 men after renal transplantation who were on either Cyclosporin A (CSA) (8 men) or a combination of azathioprine and prednisone (AZP) (16 men) as immunosuppressive therapy. The different regimes were not associated with any differences in clinical or hormonal (LH, FSH, prolactin, testosterone, estradiol) indices of testicular function although adrenal androgen (dehydroepiandrosterone sulphate) was suppressed in prednisone-treated men. Overall, however, poor graft function was associated with abnormal testicular function. Renal allograft function rather than immunosuppressive regime was the major determinant of gonadal function.

Obese gold thioglucose injected mice were reduced to lean control weight by food restriction. When pair fed with lean controls these animals then gained weight (were metabolically more efficient). Serum glucose was also elevated in this group (14.5 +/- 0.4 (14) vs 12.1 +/- 0.3 mmol/L, p less than 0.001). If previously obese animals were weight maintained with lean controls (by mild food restriction), serum glucose remained at control levels. The activity of the pyruvate dehydrogenase complex in heart muscle was decreased in both obese and pair fed previously obese, whilst it was similar to that of lean controls in the weight maintained previously obese and in obese mice actually dieted. In all obese and previously obese animals serum insulin was elevated. In hearts from control animals subjected to mild food restriction the pyruvate dehydrogenase complex was activated (11.53 +/- 1.80 (5) vs 3.34 +/- 0.62 (9) U/g dry weight), despite a reduced serum insulin level (42 +/- 2 vs 74 +/- 10 microU/ml, p less than 0.01). These diverse changes in the proportion of the pyruvate dehydrogenase complex in the active form and insulin levels argue for a persistent alteration in the sensitivity of the pyruvate dehydrogenase complex to insulin in obesity, as well as indicating that glucose metabolism in obese animals is altered by both body weight and diet amount.

Pyruvate dehydrogenase complex activity is the major determinant of glucose oxidation in animal cells. Tissue glucose oxidation is reduced in obesity and states of insulin resistance and alternate fuels are utilized for energy and pyruvate dehydrogenase activity is reduced in cardiac muscle in obesity. The effect of four different diets (standard laboratory chow, high-carbohydrate, high-protein and high-fat) on weight gain, cardiac pyruvate dehydrogenase activity (PDHa) and serum insulin, glucose and free fatty acids was studied in the gold thioglucose obese mouse. All four diets produced significant weight gain in the gold thioglucose injected animal. Cardiac PDHa was influenced by both obesity and diet composition. The obese chow-fed animals had significantly reduced PDHa. On high-carbohydrate and high-protein feeding lean controls had a significant decrease in cardiac PDHa compared to chow-fed controls, but only in high-carbohydrate-fed animals was this further reduced by obesity. High-fat feeding produced a rapid and almost complete suppression of PDHa in both lean and obese animals. Serum insulin, glucose and free fatty acids were also affected by diet as well as obesity. The highest serum insulins were found in chow-fed obese animals whereas the highest serum glucoses were in high-carbohydrate-fed obese animals. Hyperinsulinaemia did not develop in the high-fat-fed obese animal, but the highest serum free fatty acids were found in high-fat feeding. It is concluded that both diet composition and obesity affect cardiac PDHa and therefore glucose utilization in this tissue. Insulin resistance in the acute stages of obesity development is also affected by diet composition.

We studied the effects of sleep apnea on neuroendocrine function in a cross-sectional study of 225 consecutive men undergoing sleep studies and in a longitudinal study of 43 men with severe obstructive sleep apnea before and after 3 months of successful treatment with nasal continuous positive airways pressure to eliminate upper airways obstruction. Blood samples were collected at 0600-0630 h on awakening for measurement of plasma insulin-like growth factor I (IGF-I), total and free testosterone, sex hormone-binding globulin (SHBG), LH, FSH, PRL, T4, T4-binding globulin, and cortisol. The plasma hormone levels were analyzed in relation to the severity of sleep apnea, as indicated by the desaturation index (the hourly rate of episodes of arterial oxygen desaturation greater than 4% of the stable baseline) and the mean minimal oxygen saturation during the desaturation episodes. In the cross-sectional study plasma IGF-I, free and total testosterone, and SHBG levels were significantly lower in relation to the severity of sleep apnea, whereas plasma LH, FSH, PRL, T4, T4-binding globulin, and cortisol were not. The decreases in plasma IGF-I and total and free testosterone were independent of the effects of aging and adiposity by covariance analysis. In the longitudinal study plasma IGF-I, total testosterone, and SHBG, but not free testosterone, significantly increased after 3 months of nasal continuous positive airways pressure treatment. We conclude that sleep apnea causes reversible neuroendocrine dysfunction in men, which is manifested by decreased plasma. IGF-I, testosterone, and SHBG levels. This neuroendocrine dysfunction is related to the severity of the sleep apnea, as indicated by the nadir levels of arterial oxygen desaturation and the rate of desaturation episodes. These hormonal measurements may provide biochemical markers for both the severity of sleep apnea and its response to therapeutic intervention. In addition, sleep apnea may be a previously unrecognized confounder of the neuroendocrine correlates of aging.

A 20-question multiple choice questionnaire on nutrition knowledge, health care and exercise was developed and validated (Cronbach alpha 0.83). When applied to a population of the obese and overweight, these individuals scored well (63.5 +/- 1.4 per cent) compared to other hospital patients (50.2 +/- 1.7 per cent), and out-patients (47.7 +/- 2.3 per cent). There was no difference between scores in patients presenting to a hospital clinic (who were heavier) and those presenting in the community. Even allowing for age and sex, the obese and overweight scored better than other groups (P less than 0.005). There was no relationship between knowledge score and weight. A group of overweight patients with non-insulin-dependent diabetes mellitus scored poorly (42.3 +/- 2.3 per cent). From this study it was apparent that good nutrition and health care knowledge is not necessarily related to good weight control, other factors seem limiting in this sample. The questionnaire itself may be used to assess whether change in knowledge following nutrition education is related to weight loss.