Undergraduate medical education.

Pressures from students and teachers, from professional bodies, and from changes in the way health care is delivered are all forcing a rethink of how medical students should be taught. These pressures may be more intense in London but are not confined to it. The recommendation the Tomlinson report advocates that has been generally welcomed is for more investment in primary care in London.

Effect of metyrapone on the pituitary-adrenal axis in depression: relation to dexamethasone suppressor status.

It has been suggested that the well-documented hypercortisolaemia found in a proportion of patients with severe depression occurs either in response to excessive secretion of corticotrophin-releasing hormone-41 (CRH-41) from the hypothalamus, or as a consequence of up-regulation of pituitary CRH-41 receptors. The attenuation of the normal ACTH response to CRH-41 in these subjects is thought to result from inhibition of corticotrophin secretion by elevated cortisol levels. We tested these hypotheses by examining ACTH responses to metyrapone, an 11 beta-hydroxylase inhibitor which blocks the formation of cortisol, followed by CRH-41 in 15 severely depressed in-patients diagnosed according to DSM-IIIR criteria.

Plasma atrial natriuretic peptide and renin-aldosterone in patients with cirrhosis and ascites: basal levels, changes during daily activity and nocturnal diuresis.

Measurements of plasma atrial natriuretic peptide concentrations at 8 AM showed raised levels in 21 patients with cirrhosis and ascites (10.5 +/- 0.8 pmol/L) compared with levels in 10 age-matched controls (4.

Regeneration of axons in the optic nerve of the adult Browman-Wyse (BW) mutant rat.

We have studied the regeneration of axons in the optic nerves of the BW rat in which both oligodendrocytes and CNS myelin are absent from a variable length of the proximal (retinal) end of the nerve. In the optic nerves of some of these animals, Schwann cells are present. Axons failed to regenerate in the exclusively astrocytic environment of the unmyelinated segment of BW optic nerves but readily regrew in the presence of Schwann cells even across the junctional zone and into the myelin debris filled distal segment.

Microcephaly, focal segmental glomerulonephritis and marfanoid habitus in two sibs.

Two female sibs aged 15 and 18 years with microcephaly, mental retardation and marfanoid habitus who developed focal segmental glomerulonephritis leading to renal failure are described. This combination of features appears to represent a unique syndrome distinct from previous reports of microcephaly in association with the nephrotic syndrome. The mode of inheritance is likely to be autosomal recessive.

Explanation at the opioid receptor level for differing toxicity of morphine and morphine 6-glucuronide.

The radiolabelled opioid receptor binding affinities of morphine and its active metabolite morphine 6-glucuronide at the total mu, mu 1, mu 2 and delta receptors were determined. Morphine 6-glucuronide was found to have a 4-fold lower affinity for the mu 2 receptor (IC50 17 nM and 82 nM for morphine and morphine 6-glucuronide respectively, P = 0.01), the receptor postulated to be responsible for mediating the respiratory depression and gastrointestinal effects after morphine.

Clinical significance of primitive reflexes in Alzheimer's disease.

Study Objective: To establish the relationship between cognition, behavior, function, and clinical characteristics on the one hand, and the presence of primitive reflexes (PR) (pout, snout, palmomental and grasp) in patients with Alzheimer's disease (AD).

Design: Cross-sectional survey.

Setting: Secondary care geriatric practice specializing in the assessment of cognitive impairment.

The impact of the appearance of the anaesthetist on the patient's perception of the pre-operative visit.

The clinician's appearance is often considered a symbol which identifies and defines specific characteristics of the individual. Opinion of both lay and medical personnel on appropriate clothing inclines towards formal dress. Our aim was to assess the effect of the anaesthetist's appearance during a ward visit on the patient's evaluation of either the visit or the anesthetist himself.

Involvement of calmodulin in depolarization-induced release of corticotrophin-releasing hormone-41 from the rat hypothalamus in vitro.

We have employed an acute explant system of the rat hypothalamus in vitro, as previously described, to examine the role of calcium and calmodulin in the release of corticotrophin-releasing hormone-41 (CRH-41). Release of CRH-41, as determined by radioimmunoassay, was stimulated in a dose-dependent manner by the membrane-depolarizing agents KCl and veratridine. Stimulation was also observed with the calcium ionophore A23187.

Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome.

Objective: To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome.

Design: An evaluation of the standard clinical practice at one institution.

Patients: Ninety-one patients with Cushing's syndrome: 57 pituitary-dependent Cushing's disease, 10 adrenocortical adenomas, six adrenocortical carcinomas and 18 ectopic ACTH syndrome.

The influence of steroid therapy and recombinant human erythropoietin on the growth of children with renal disease.

Long-term steroid therapy has a depressant effect on hypothalamo-pituitary pulsatile secretion of growth hormone (GH), and this results in an attenuated pubertal growth spurt. Oxandrolone and recombinant human GH improve growth rates in children taking long-term steroid therapy for renal disease, but there are potential side effects. Treatment with recombinant human erythropoietin improved the growth of three prepubertal, but not three pubertal haemodialysis patients.

Megavoltage pituitary irradiation in the management of prolactinomas: long-term follow-up.

OBJECTIVE To determine the long-term effects of external beam megavoltage radiotherapy (RT: 4500 cGy via three portals at 180 cGy or less total daily dose) on endocrine function in prolactinomas. DESIGN Longitudinal study following radiotherapy with periodic re-assessment at regular intervals, at least 2 months off dopamine agonist therapy. PATIENTS Thirty-six female patients, age range 19-50 years, with either macroprolactinomas (12 patients) or microprolactinomas (24 patients), but without significant suprasellar extensions.

Do attitudes towards persons with handicaps really shift over time? Comparison between 1975 and 1988.

A replication of a study by Spreen (1977) was conducted to assess whether a positive shift in attitudes towards persons with mental retardation has occurred. Undergraduate students (N = 191) were tested. Results compared to those of Spreen (1977) showed a positive shift over the 13-year period.

The effects on anterior pituitary hormone secretion of salmon calcitonin in healthy volunteers.

The reports of the effect of calcitonin on pituitary function are confusing and often refer to uncontrolled studies. We have now carried out a double-blind placebo-controlled trial of intravenous and subcutaneous salmon calcitonin on anterior pituitary function in 17 healthy volunteers. Visual analogue scores for the nausea and vomiting seen after salmon calcitonin correlated with the rise in ACTH and, secondarily, cortisol.

Simultaneous determination of clebopride and a major metabolite N-desbenzylclebopride in plasma by capillary gas chromatography-negative-ion chemical ionization mass spectrometry.

A procedure for the simultaneous assay of clebopride and its major metabolite N-desbenzylclebopride in plasma has been developed. The method utilizes capillary gas chromatography-negative-ion chemical ionization mass spectrometry with selected-ion monitoring of characteristic ions. Employing 2-ethoxy analogues as internal standards, the benzamides were extracted from basified plasma using dichloromethane.

Variable methylation of the 5'-flanking DNA of the human pro-opiomelanocortin gene.

The pro-opiomelanocortin gene is widely expressed in human tissues, although both transcriptional initiation sites and regulation appear to be tissue specific. In order to determine how promoter and enhancer choice is effected, we have studied the methylation pattern of the gene in a number of normal tissues, tumours and cell lines. Variability of this pattern was observed in the 5'-flanking DNA, particularly at the HpaII site located at -304 bp upstream from the pituitary CAP site.

Effect of tetrahydroaminoacridine on cognition, function and behaviour in Alzheimer's disease.

Objective: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer's disease.

Design: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration.

Setting: Referral-based geriatric practice in a community hospital.

Interleukins-1 and -6 stimulate the release of corticotropin-releasing hormone-41 from rat hypothalamus in vitro via the eicosanoid cyclooxygenase pathway.

It has previously been shown that interleukin-1 (IL-1) directly stimulates the release of CRH-41 from rat hypothalamus in vitro, suggesting that cytokines may mediate the effects of changes in immune state on the hypothalamo-pituitary adrenal axis (HPA). However, it is likely that several cytokines can cause changes in neuroendocrine function, and we have now investigated a series of others for central activity on the HPA: IL-2, IL-6, IL-8, tumor necrosis factor (cachectin), interferon-alpha 2, and interferon-gamma. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubation, and estimation of CRH-41 concentrations in the medium by a specific RIA; the acute effects of cytokines on ACTH release from rat dispersed pituitary cells were also measured.

Human atrial natriuretic factor and renin-aldosterone in paracetamol induced fulminant hepatic failure.

It has been postulated that deficiency of a putative natriuretic factor, or resistance to such a factor, may contribute to sodium retention in fulminant hepatic failure. Levels of plasma human atrial natriuretic factor (h-ANF), plasma renin activity, and aldosterone concentration were measured in 33 patients with fulminant hepatic failure due to paracetamol overdose, and 12 healthy control subjects. Levels of h-ANF were raised only in patients with evidence of severe renal impairment (serum creatinine greater than 300 mumol/l and urine output less than 100 ml/24 hours).

In vitro and in vivo analysis of the processing and fate of the peptide products of the short proopiomelanocortin mRNA.

Many peripheral tissues express the proopiomelanocortin (POMC) gene as an 800-base mRNA that lacks the 5' end of the 1200-base pituitary transcript. The missing region encodes the peptide signal sequence, and thus, it is unlikely that any translation product would be secreted. We have found that a RNA transcript equivalent to this short message, generated by transcription in vitro from a T7 polymerase promoter, is translatable in a rabbit reticulocyte lysate, generating peptides of 27.