The insulin response to intravenous fructose in maturity-onset diabetes mellitus and in normal subjects.

Insulin responses to intravenous fructose and glucose were measured in 15 patients with maturity-onset diabetes mellitus. In eight patients given fructose first the insulin responses to fructose and glucose were similar. In seven patients given glucose first the insulin response to subsequently infused fructose was significantly greater than to glucose. Multiple regression analysis showed that the ratio of the fructose to glucose insulin response, assessed by area under the insulin serum concentration-time curve (F/G ratio) in individual patients, correlated most closely with prefructose infusion plasma glucose. Similar analysis, applied to results in 27 normal subjects, showed that the most important determinant of the insulin response to fructose in this group also was the immediate prefructose infusion plasma glucose. Thus in diabetics, as in normal controls, the response of the beta cell to intravenous fructose appears to be sensitively set by the ambient plasma glucose concentration at the onset of fructose infusion.

The effect of etomidate on adrenocortical function in dogs before and during hemorrhagic shock.

The effects of the hypnotic agent ethyl phenylethyl imidazole carboxylate (etomidate), on corticosteroidogenesis were studied in greyhound dogs during a 2-h period of anesthetic followed by a further 2 h of anesthetic combined with hemorrhage. Three groups of dogs were studied. The first, a control, received thiopentone and pentobartitone for induction and maintenance of anesthesia. A second control group received the chemically unrelated hypnotic preparation, althesin, after induction with thiopentone and pentobarbitone. In the first control group and the althesin-treated control group, changes in plasma ACTH and in plasma renin and angiotensin II concentrations were followed closely by changes in the levels of their respective dependent corticosteroids. A third experimental group received etomidate after induction of anesthesia with thiopentone and pentobarbitone. In these, in contrast, plasma levels of progesterone, 17 alpha-hydroxyprogesterone, corticosterone, cortisol, and aldosterone decreased during the experiment even failing to respond to massive rises in plasma ACTH concentration, renin, and angiotensin II levels after hemorrhage. However, the ability of 11-deoxycortisol and 11-deoxycorticosterone to respond was retained. These results suggest that etomidate inhibits corticosteroidogenesis directly, probably acting at more than one point in the biosynthetic pathway. It is suggested that it inhibits mitochondrial steroid hydroxylation (e.g. side chain cleavage, 11 beta-hydroxylation), but not 21-hydroxylation which occurs outside the mitochondrion.

Inhibition by etomidate of steroidogenesis in isolated bovine adrenal cells.

Adverse side effects of the anaesthetic etomidate have been indirectly linked with inhibition of adrenocorticoid synthesis. The present in vitro study has shown that this is a direct effect and indicated which biosynthetic reactions are affected by etomidate. Isolated bovine adrenocortical cells were incubated with and without 10(-8)M ACTH and with increasing doses of etomidate (0-625 ng/ml). ACTH-stimulated cortisol synthesis was significantly inhibited by a concentration of etomidate (25 ng/ml), which is much less than therapeutic plasma levels (100-500 ng/ml). Both basal and ACTH stimulated synthesis of cortisol, progesterone, 17 alpha hydroxyprogesterone and corticosterone were inhibited by 625 ng etomidate/ml whereas deoxycorticosterone output was more than doubled with this dose of anaesthetic. These observations suggest that etomidate inhibits mitochondrial cytochrome P450-dependent hydroxylation reactions in the adrenal steroidogenic pathway.

Effect of indapamide on blood pressure and glucose tolerance in non-insulin-dependent diabetes.

Ten hypertensive non-insulin-dependent diabetic patients were treated with the antihypertensive drug indapamide to assess its effect on glucose tolerance over 1 year. Both systolic and diastolic blood pressures fell significantly (p less than 0.001) over the first month of treatment, and no change in plasma glucose or plasma insulin levels during an oral glucose tolerance test occurred at any time. Indapamide is an effective antihypertensive drug and, in contrast to thiazide diuretics, has no adverse effect on glucose tolerance in non-insulin-dependent diabetic patients.

Serum androgens and gonadotrophins in bronchial carcinoma.

The concentrations of testosterone, free testosterone index derived by two independent techniques (FTI1, FTI2), dehydroepiandrosterone sulphate (DHAS), androstenedione (AND), luteinizing hormone (LH), follicle stimulating hormone (FSH), and sex hormone binding globulin (SHBG) were measured in 38 healthy male controls aged between 40 and 60 years (Group 1) and in 52 male patients with bronchial carcinoma of whom 28 were aged between 40 and 60 years (Group 2) and 24 were aged over 60 years (Group 3). Compared with Group 1, testosterone, FTI1, FTI2, and DHAS were significantly lower (P < 0.001), AND and LH were significantly higher (P < 0.001) and there was no significant difference in FSH or SHBG, in Group 2. No significant difference between Groups 2 and 3 was found for any variable. Analysis of covariance for Groups 2 and 3 combined, showed testosterone, FTI1 and FTI2 were significantly lower in the presence of metastases. These results suggest a more widespread abnormality of androgen metabolism in male patients with bronchial carcinoma than a simple reduction in serum testosterone; DHAS is also significantly reduced while AND is significantly increased. The primary abnormality appears to be at testicular and/or adrenal level as pituitary function appears normal as witnessed by compensatory increases in LH.

Magnetic resonance findings in sarcoidosis of the thorax.

Fifteen patients with sarcoidosis underwent thoracic MRI examinations. The T2 signal intensity of lymphadenopathy varied, with no characteristic pattern noted. Three of four patients with bright lymph nodes on T2 images had stage I sarcoidosis, but low intensity nodes were also seen in stage I patients. Coronal images were complementary to axial images and better depicted subcarinal adenopathy. MRI does not distinguish the lymphadenopathy of sarcoidosis from other entities, but is useful for defining the anatomic extent of disease and differentiating pulmonary artery enlargement from adenopathy.

Effects of Trypanosoma congolense on pituitary and adrenocortical function in sheep: changes in the adrenal gland and cortisol secretion.

The effect of trypanosomiasis on adrenal function was studied in 10 pubertal Scottish blackface rams infected with Trypanosoma congolense and nine uninfected controls. Plasma cortisol concentration was measured by radioimmunoassay in samples obtained twice a week for three weeks before infection and three times a week for 79 days after infection. There was a significant (P < 0.001) increase in cortisol concentration in all the infected rams after the onset of parasitaemia nine to 16 days after infection. This was followed by a transient non-significant decrease in cortisol levels between 19 and 41 days and a variable and parasitaemia-dependent increase in cortisol levels between 44 and 79 days after infection. Marked hypertrophy of the zona fasciculata-reticularis, infiltration of mononuclear cells into the cortical and medullary zones, hyperaemia and focal coagulative necrosis were evident in the adrenal glands of infected rams killed at the end of the study. Trypanosome infection induced a low grade persistent pyrexia, marked anaemia, reduced growth rates and general loss of body condition. These results demonstrate that T congolense infection in sheep causes marked pathological changes in the adrenal cortex and changes in the secretion of cortisol.

Effects of Trypanosoma congolense on pituitary and adrenocortical function in sheep: responses to exogenous corticotrophin-releasing hormone.

To investigate whether the aberrations in adrenocortical and gonadal activity observed in trypanosomiasis may be induced by the refractoriness of the pituitary to hypothalamic liberins, the responses of the pituitary and adrenal glands and the testes to stimulation with ovine corticotrophin-releasing hormone (oCRH) were studied in rams 23 days (acute phase) and 65 days (chronic phase) after they were infected with Trypanosoma congolense. On both occasions a peak of plasma ACTH was observed within 20 minutes of the injection of CRH but the rate of increase in ACTH and the mean peak values in the infected rams were significantly lower (P < 0.001) on day 23 but higher (P < 0.05) on day 65 than in the uninfected control rams. Plasma cortisol concentration increased in all the rams after the injection of CRH. The rate of increase in plasma cortisol and the mean peak values were not significantly different between the control and infected rams on day 23 but were significantly (P < 0.001) higher in the infected rams on day 65. However, the post peak concentrations of ACTH declined more rapidly in the infected rams than in the controls on both days 23 and 65. The plasma concentration of luteinising hormone (LH) did not change after the injection of CRH, whereas the testosterone levels showed a delayed response and its concentration increased when plasma ACTH and cortisol concentrations declined in both groups. On day 23, there was a greater increase in testosterone in the infected than in the control rams.(ABSTRACT TRUNCATED AT 250 WORDS)

Giant varices in portal hypertension: CT findings.

Two cases of giant varices in portal hypertension are presented. Dynamic computed tomography (CT) was useful in establishing that the masses were in fact dilated veins.

Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome.

OBJECTIVE: To study the dynamic function of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. DESIGN: Prospective comparison of patients with postviral fatigue syndrome with two control groups. SETTING: Department of neurology, University of Glasgow, Southern General Hospital; department of psychiatry, St James's Hospital, Dublin. SUBJECTS: 15 patients with postviral fatigue syndrome, 13 age and sex matched healthy subjects, and 13 patients with primary depression. MAIN OUTCOME MEASURES: Serum prolactin concentrations before and one, two, and three hours after administration of buspirone. RESULTS: Because of the effects of sex hormones on prolactin secretion data for men and women were analysed separately. There was no significant difference in baseline prolactin concentrations between patients with postviral fatigue syndrome and healthy subjects or those with primary depression. However, the percentage difference between peak and baseline values was significantly higher in patients with postviral fatigue syndrome than the control groups (one way analysis of variance: women, p = 0.003; men, p = 0.004). CONCLUSIONS: The results suggest upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome but not in those with primary depression. The buspirone challenge test may therefore be useful in distinguishing these two conditions. Larger studies are required to explore the potential value of drugs acting on central 5-hydroxytryptamine receptors in the treatment of patients with the postviral fatigue syndrome.

Failure of somatostatin analogue SMS 201-995 to control Cushing's syndrome due to ectopic release of ACTH from a bronchial carcinoid.

A patient with ectopic Cushing's syndrome secondary to a malignant thymic carcinoid tumour was treated with the somatostatin analogue SMS 201-995. The administration of the drug subcutaneously in increasing doses over a 34 day period failed to control the ACTH or glucocorticoid excess.

Thyrotropin receptor antibodies associated with post-operative relapse of thyrotoxicosis in a pregnancy complicated by neonatal thyrotoxicosis.

This case describes the clinical, biochemical and immunological features associated with relapse of thyrotoxicosis during pregnancy in a patient who had recently undergone a subtotal thyroidectomy for Graves' disease. The baby, shortly after birth, showed clinical and biochemical features of thyrotoxicosis which responded to carbimazole therapy. Thyrotropin receptor antibodies and thyroid stimulating antibodies were present in the blood of the mother and baby. The clinical course of the neonatal thyrotoxicosis correlated with the TSH receptor antibody levels.

The incidence of clinical thyroid dysfunction in an unselected group of pregnant and post partum women.

This study has examined the incidence of thyroid dysfunction during pregnancy and up to six months post partum in 65 women attending an antenatal clinic in the West of Scotland. Five were found to be positive for thyroid antibodies at presentation and in these the antibody titre fluctuated during pregnancy and in the post partum period. One patient developed thyroglobulin antibodies post partum. Mean total T3 and total T4 levels rose during pregnancy but had normalised by six weeks post partum. The changes in FT4 and TBG levels observed during pregnancy did not normalise until after six weeks post partum. Only one patient developed any biochemical evidence of thyrotoxicosis post partum and this was not found to be associated with the presence of thyroid antibodies. No patient showed any evidence of hypothyroidism.

Cold-pressed flaxseed oil reverses age-associated depression in a primary cell-mediated adaptive immune response in the mouse.

The objective of this investigation was to determine the influence of flaxseed oil on responses representative of primary humoral and cell-mediated adaptive immune competence in immunosenescent mice. Male and female C57BL/6J mice, 85 weeks old, were randomized between two complete purified diets differing only in oil source (cold-pressed safflower or flaxseed). After 8 weeks, humoral competence was assessed in six mice per group as the serum haemagglutinin titre to sheep red blood cells (SRBC) and cell-mediated competence was assessed, in an additional six mice per group, as the delayed hypersensitivity response to SRBC. A zero-time control group (88 weeks old) and a young adult positive control group (12 weeks old) were each tested similarly (six per immune response), revealing age-related depression in both antibody and cell-mediated competence at 88 weeks of age. After the 8-week experimental period, the antibody response of the two test groups of geriatric mice remained below the young adult level (P=0.04) and the cell-mediated response of the safflower oil group also continued to exhibit age-related depression (20 % of young adult level, P=0.0002). By contrast, the anti-SRBC delayed hypersensitivity response of the flaxseed group no longer differed from the response of the young adults but exceeded that of the safflower and zero-time control senescent groups (P=0.0002). Depression in primary cell-mediated competence, the most outstanding aspect of immunosenescence, can be addressed by means of a dietary source of 18 : 3n-3 without longer-chain PUFA.

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.

Anatomic variations and abnormalities in the diaphragm seen with US.

The authors report their experience with diaphragmatic structures that simulate intrahepatic masses at abdominal ultrasonography (US). In a series of 74 patients, diaphragmatic slips were the most common finding (34 patients). The slips could be differentiated from masses by scanning along their long axis to demonstrate elongated structures with multiple linear echoes. Scalloping of the diaphragm, associated with multiple slips, was seen in 10 patients. Partial eventration was found in 23. Inversion of a hemidiaphragm, caused by a large pleural effusion or intrathoracic mass, was seen in 13 patients. Pleural masses affecting the diaphragm were seen in 13 patients; focal hypertrophy of a diaphragmatic crus simulated a mass in three. Real-time US allowed the differentiation of diaphragmatic abnormalities from lesions.

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.