PubMed HealthSearch

Biomedical subjects

W J Jeffcoate

Publications and source records attributed to W J Jeffcoate.

At least 19 recordsLinked to original sources

The short Synacthen test in acute hospital admissions.

OBJECTIVE: We wished to define the cortisol response to 250 micrograms intramuscular tetracosactrin (Synacthen) in acute hospital admissions, using a modern immunoassay for cortisol. DESIGN: We performed a prospective study of, as near as possible, a consecutive series of 161 admissions to a single unit. PATIENTS: We studied 50 patients (age range 67-98, mean 80.3 years, 31-female, 19-male) admitted as an emergency, from whom it was possible to obtain informed consent, and whom it was possible to study within 24 hours of admission. MEASUREMENTS: We measured baseline, increment and peak serum cortisol following administration of 250 micrograms intramuscular tetracosactrin between 0800 and 0900 hours. RESULTS: Baseline cortisol concentrations ranged from 288 to 1585 nmol/l (mean 706; median 665). Peak cortisol concentrations ranged from 602 to 2265 nmol/l (mean 1076; median 999). Baseline and peak cortisol concentrations showed a significant correlation (P less than 0.001). Increment varied from 10 to 747 nmol/l (mean 374; median 336) and did not correlate with baseline. CONCLUSIONS: In acute hospital admissions, baseline serum cortisol between 0800 and 0900 hours should exceed 250 nmol/l. Peak serum cortisol after 250 micrograms intramuscular tetracosactrin should exceed 600 nmol/l. Calculation of the increment is of no value.

Acute Disease

Perceived needs of general practitioners and practice nurses for the care of diabetic patients.

This study compared the aims and needs of General Practitioners (GPs) and practice nurses who wished to improve the service they provided for non-insulin-treated diabetic patients. Contact was made with 242 GPs in 110 practices in Central and North Nottingham, and a questionnaire was sent to the 149 (62%) who requested one. Completed questionnaires were returned by 110 (74%) of these, and by 48 (80% of 60) of their practice nurses. Only 19 GPs ran a specific diabetic clinic, but nearly all (95%) wanted to improve the service they provided for diabetes care. In doing so, many wished for involvement of opticians, chiropodists, and dietitians, and all wished to involve the practice nurse. The need for involvement of hospital-based diabetes specialist nurses was perceived by only 37% GPs. More than two-thirds (69%) of practice nurses wanted more input into the care of diabetes. Both GPs and practice nurses felt that the role of the practice nurse should include screening for complications, although there was some disagreement about the extent of this involvement. GPs envisaged that patient education would be a major problem in establishing a diabetes service, but only 58% identified education as a task that could be accomplished by the practice nurse.

Attitude of Health Personnel

Effect of phase of menstrual cycle on insulin sensitivity, peripheral blood flow and cardiovascular responses to hyperinsulinaemia in young women with type 1 diabetes.

Disturbances of blood glucose control around the time of menstruation are often reported by women with Type 1 diabetes. To investigate the possibility that such changes may be due to alterations in insulin sensitivity or peripheral blood flow we have studied 9 women with Type 1 diabetes during the follicular and luteal phases of the menstrual cycle. Insulin sensitivity was assessed by the glucose clamp technique with insulin doses of 40 (low dose) and 100 (high dose) mU m-2 min-1. Glucose disposal rates were 2.5 +/- 0.3 (mean +/- SE) mg kg-1 min-1 during the follicular phase and 3.2 +/- 0.3 mg kg-1 min-1 in the luteal phase with low dose insulin, and 5.9 +/- 0.4 and 6.4 +/- 0.6 mg kg-1 min-1, respectively, with high dose insulin. These differences were not statistically significant. Forearm blood flow, heart rate, and blood pressure were similar during both phases.

3-Hydroxybutyric Acid

Autonomic neuropathy and the pathogenesis of glaucoma in diabetes mellitus.

In order to determine whether ocular hypertension and glaucoma may be a complication of autonomic neuropathy in diabetes mellitus, 30 asymptomatic diabetic patient volunteers were studied. A correlation was sought between reduced anterior chamber depth which is thought to predispose to the development of glaucoma, and two markers of autonomic dysfunction, loss of sinus arrhythmia and reduced diameter of dark adapted pupils. A significant correlation was found between reduced chamber depth and pupil diameter arrhythmia (r = 0.36, p = 0.025) and between chamber depth and pupil diameter (r = 0.45, p = 0.006). As expected, there was also a significant correlation between sinus arrhythmia and pupil diameter (r = 0.68, p less than 0.001). The correlation between pupil diameter and sinus arrhythmia, and between pupil diameter and chamber depth was preserved after the data were adjusted for age (r = 0.54, p less than 0.001 and r = 0.35, p = 0.03, respectively), while that between sinus arrhythmia and chamber depth was lost (r = 0.23, NS). No association was found between intraocular pressure and either marker of autonomic dysfunction, but intraocular pressure was not abnormal (less than 22 mmHg) in any individual case. These data suggest that autonomic denervation of the eye in diabetes may be associated with alteration of anterior chamber depth.

Adult

Diabetes insipidus complicating myelofibrosis.

A 68 year old man developed cranial diabetes insipidus 3 years after the diagnosis of myelofibrosis, coincident with a marked increase in nucleated cell count. No mass lesion was demonstrable on computed tomographic or magnetic resonance imaging. It is suggested that hypothalamic damage was caused by local infiltration or infarction, a complication of myelofibrosis which has not previously been reported.

Animals

Comparison of high fibre diets, basal insulin supplements, and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE: To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN: Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING: Teaching hospital diabetic clinics. PATIENTS: 33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS: During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT: Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS: No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS: High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.

Blood Glucose

Prevention of effects of alcohol intoxication by naloxone.

In a double-blind, cross-over study of twenty male volunteers intravenous injection of 0.4 mg naloxone prevented the impairment of psychomotor performance induced by low levels of blood alcohol. The possibility that alcohol produces intoxication by stimulating the release of endogenous opioid peptides should be investigated.

Adult

The circadian variation of immunoreactive lipotrophin and its relationship to ACTH and growth hormone in man.

There is a clear circadian rhythm of plasma immunoreactive LPH in man with the trough occurring between 22.00 h and 03.00 h and the peak between 07.00 h and 08.00 h, immediately after waking. At all times circulating LPH and ACTH levels follow each other closely. However, no correlation was observed between LPH levels and either plasma GH or the stage of sleep.

Adrenocorticotropic Hormone

Psychiatric manifestations of Cushing's syndrome: response to lowering of plasma cortisol.

The incidence of psychiatric abnormalities has been assessed in 38 patients with Cushing's syndrome and two with alcohol-induced pseudo-Cushing's syndrome. Twenty-six patients were examined by one of us using a standardized psychiatric interview, and this group included all those with severe to moderate psychiatric disorders. Depression was the commonest symptom: five patients (13%) were markedly or severely depressed, four (10%) were moderately depressed and 13 (32%) were mildly depressed. Four patients exhibited other, non-depressive psychiatric symptoms and only 14 (35%) were judged free from psychiatric abnormality. The first line of treatment was to reduce the circulating cortisol level either by adrenalectomy or by treatment with oral metyrapone; both patients with alcohol-induced pseudo-Cushing's syndrome were treated by alcohol withdrawal. Once the plasma cortisol level was successfully controlled, depressive symptoms were relieved in all five patients with marked or severe depression and in three of the four who were moderately depressed. Mild depressive symptoms were relieved in six of the 13 affected. It is concluded that metyrapone may be of considerable value in the management of the acute psychiatric states which may occur in Cushing's syndrome and these findings are discussed in the light of their possible pathogenesis.

Adolescent

Hormonal and metabolic responses to an enkephalin analogue in normal man.

An enkephalin analogue [D-Ala2, MePhe4, Met(o)-ol] enkephalin (DAMME), given intravenously to normal subjects raised serum prolactin and growth-hormone levels but lowered serum levels of luteinising hormone, follicle-stimulating hormone, cortisol, and corticotrophin. There was also a small fall in total glucagon and gastric inhibitory peptide (G.I.P.) and a rise in thyrotrophin. beta-Lipotrophin, motilin, vasoactive intestinal peptide, insulin, gastrin, and pancreatic glucagon were unchanged. Blood-glycerol increased, and blood lactate, alanine, and glucose fell. Prior administration of the opiate antagonist, naloxone, attenuated the hormonal responses to DAMME. This enkephalin analogue produces endocrine and metabolic changes in man which may be mediated through opiate-binding receptors both within and outside the brain. The enkephalins and related substances may provide an important link between perception, behaviour, and neuroendocrine regulation of hormone secretion and metabolism.

Adrenocorticotropic Hormone

beta-Endorphin in human cerebrospinal fluid.

beta-endorphin is a brain peptide with potent morphine-like activity structurally related to the anterior pituitary hormone beta-lipotrophin (beta-L.P.H.). We have developed a radioimmunoassay for human beta-endorphin in plasma and cerebrospinal fluid (C.S.F.). Since the antiserum also reacts with beta-L.P.H., beta-endorphin was distinguished by using a second antiserum which measures beta-L.P.H. alone. With these two immunoassay systems and gel chromatography, we found beta-endorphin in all 20 C.S.F. samples tested at a concentration always higher than, but with no other relationship to, that in plasma. beta-endorphin was found in C.S.F. of patients who had hypopituitarism and undetectable plasma-beta-endorphin, suggesting that it is synthesized in the brain rather in the pituitary.

Adult

A specific radioimmunoassay for human beta-lipotropin.

A homologous RIA for human beta-lipotropin (beta hLPH) has been developed. At a final dilution of 1:24,000, the antiserum employed shows cross-reaction with beta hLPH but none with human beta-MSH (beta hMSH), and it is concluded that the antigenic determinant lies within the N-terminal 1-36 region of beta hLPH. With extraction of 3-ml plasma samples, the assay is sufficiently sensitive to measure circulating beta hLPH levels in normal individuals at 0900 h (25-200 pg/ml). There is a circadian variation with levels falling to (less than 20-80 pg/ml) at 2300 h. beta hLPH levels rise after metyrapone and after insulin-induced hypoglycemia, and fall after administration of dexamethasone. In patients with a variety of diseases of the pituitary-adrenal axis, levels of beta hLPH follow immunoreactive ACTH levels, although the two are not always secreted on a 1:1 molar basis.

Humans