PITUITARY ACTH DEPENDENT CUSHING''S SYNDROME DUE TO ECTOPIC PRODUCTION OF A BOMBESIN-LIKE PEPTIDE BY A MEDULLARY CARCINOMA OF THE THYROID

A 41-year-old man presented with Cushing's syndrome and the biochemical features of ectopic ACTH production. Investigation revealed mediastinal metastases from a medullary carcinoma of the thyroid. The peripheral plasma contained grossly elevated levels of bombesin-like immunoreactivity (irBombesin) as well as calcitonin; blood sampling via a venous catheter confirmed a gradient of irBombesin, but not of ACTH, in the mediastinal vein draining the tumour. On extraction the tumour contained a bombesin-like peptide, but not vasopressin or corticotrophin releasing factor and only very low levels of ACTH; immunohistochemical studies showed positive immunostaining for bombesin and calcitonin but none for ACTH or CRF. No ACTH was released from dispersed tumour cells in vitro. However an extract of the tumour stimulated ACTH release in vitro from perifused dispersed rat anterior pituitary cells. This is the first reported case of Cushing's syndrome due to ectopic production of a bombesin-like peptide, causing excessive pituitary ACTH secretion.     

A Dose-Response Analysis of Methoxychlor-Induced Alterations of Reproductive Development and Function in the Rat

A Dose-Response Analysis of Methoxychlor-Induced Alterationsof Reproductive Development and Function in the Rat. GRAY, L.E., JR., OSTBY, J., FERRELL, J., REHNBERG, G., LINDER, R., COOPER,R., GOLDMAN, J., SLOTT, V., AND LASKEY, J. (1989). Fundam. Appl.Toxicol12, 92–108. In the present study rats were dosed fromweaning, through puberty and gestation, to Day 15 of lactationwith methoxychlor at 25, 50, 100, or 200 mg/kg/day. Morphologicallandmarks of puberty were measured, including the ages at vaginalopening, first estrus, and first estrous cycle in females andat preputial separation in males. In the female, estrous cyclicity,fertility, litter size, number of implantation sites, organweights, and ovarian and uterine histology were also measured.The viability of the offspring (F1) and their fertility wereevaluated using a continuous breeding protocol. Males were necropsiedafter breeding, the reproductive organs were weighed, and thecauda epididymal sperm counts were determined. One testis wasused for histopathology, while the other was used to quantifyinterstitial fluid (IF) content, IF testosterone concentration,and testicular sperm production. Testosterone and an drogen-bindingprotein were measured in the caput epididymis, and sperm motilityand morphology were evaluated from a caudal sample. The serumand pituitary were saved for hormonal determinations. Methoxychloraccelerated the age at vaginal opening and first estrus, andthe vaginal smears were cornified. Growth was retarded at 100and 200 mg/kg/day and fertility was reduced when the femaleswere bred with untreated or similarly treated males. In thehighest- dose group, the mated females went from constant estrusinto pseudopregnancy following mating, but they had no implants.In males, methoxychlor treatment markedly reduced growth, seminalvesicle weight, cauda epididymal weight, caudal sperm content,and pituitary weight. Puberty was delayed in the two highest-dosagegroups. Testicular sperm measures were much less affected thancaudal measures. Testis weight and histology were slightly affected,and testicular sperm production, sperm morphology, and motilitywere unaffected. Endocrine function of the testes and pituitarywas altered by methoxychlor administration. Leydig cell testosteroneproduction, in response to human chorionic gonadotropin challenge,was reduced and pituitary levels of prolactin, thyroid-stimulatinghormone (TSH), and follicle-stimulating hormone (FSH) were altered.In contrast, serum levels of prolactin, FSH, and luteinizinghormone were unaffected. Serum TSH was reduced by 50% of controlat 100 and 200 mg/kg/day, while pituitary levels were increased.Gonadotropin-releasing hormone concentration in the mediobasalhypothalamus was also elevated. In spite of the many reproductivealterations, the fertility of treated males was not reducedwhen they were mated with untreated females. Growth and viabilityof the offspring (F1) from the 50 mg/kg/day treatment groupwere normal, but in the females, vaginal opening was accelerated,estrous cyclicity was abnormal in the rats during middle age,and fecundity was reduced.     

An audit of responding to symptoms in community pharmacy

A two-stage audit of community pharmacists' service in response to symptoms was carried out using a previously piloted method. Pharmacists from up to 46 pharmacies completed questionnaires indicating the advice they thought should be given in each of 12 scenarios that could present to community pharmacies. The six scenarios with the highest consensus response were later enacted in the same pharmacies by researchers. Three were used in the first stage and three in the second. Meetings were held between the stages to discuss the results and suggest ways of improving them. The consensus advice, determined by the questionnaire responses, was given on only 27 per cent of all visits — 18 per cent in the first stage and 35 per cent in the second. This was mainly due to non-drug advice being omitted. “Appropriate” products were recommended in 90 per cent of first stage visits but only 74 per cent of second stage visits. “Acceptable” advice was provided in 75 per cent of all visits, with little difference between the two stages. Questioning of the researchers was “good” in 35 per cent of first stage visits and 43 per cent of second stage visits. Inadequate questioning was significantly related to inappropriate advice being given. Inappropriate advice was given on 25 per cent of all visits, with equal frequency by both pharmacists and assistants. Participating pharmacists identified many problems that could contribute to a less than ideal service but most were outside their control, such as television advertising of products and customer expectations. The use of protocols, implementation of staff training and the audit were considered to have had a positive effect on the response to symptoms service. Most participants considered that the method used was acceptable and suggested a similar method should be used on a regular basis to monitor the service.     

Urgent psychiatric transfers from prison in England and Wales: a prison perspective

Prisoners on remand are at high risk of mental illness. They have a high rate of suicide and a high incidence of psychotic illness. Provision does exist within the Mental Health Act (1983) for the emergency transfer of remanded prisoners by transfer order (section 48), but this facility is used to varying degrees throughout England and Wales. This is a retrospective case study of all patients transferred from Belrnarsh Prison under this emergency provision (S48) between April 1991 and March 1992. Twenty-two transfers were enacted (two patients on two separate occasions) during the trial period. Of these 22, 15 (68%) had a paranoid psychotic illness; 14/20 (70%) had committed serious violent offences; 14/22 (63%) were transferred to locked wards of general psychiatric hospitals; 5 (22%) went to regional secure units; 3 (14%) went to maximum secure hospitals. Rapid transfer to psychiatric hospital for all those offenders who are seriously psychiatrically ill is one of the main recommendations of a recent Department of Health/Home Office Report (Department of Health/Home Office, 1991). The existing provisions are shown to be an effective means to enact such emergency transfers. Many such transfers can be managed in the general psychiatric service.     

Pilot Study to Enhance Start-up of a Multicenter Nutrition Intervention Trial

Multicenter trials are important for answering questions that require large numbers of subjects. Such trials require standardized implementation of behavioral change programs across diverse populations, regions, and staff. Researchers involved with the Trial of Nonpharmacologic Interventions in the Elderly conducted a 17-week pilot study of their most complex intervention (combined weight and sodium reduction) before actual start-up of the main study. This allowed staff to rehearse implementing the program and to identify and address intervention and standardization issues. Registered dietitians in 4 US communities recruited 28 participants for the pilot study, using eligibility criteria similar to those for the main trial. Participant evaluations reflected high satisfaction with the program materials and overall approach. Minor protocol changes suggested by results of the pilot study were made easily in time for start-up of the main study. Reductions in weight and sodium intake were less than targeted but were sufficient to suggest that the intervention would be effective under optimal conditions. This partial achievement of goals in the pilot study underscored the need to allow for a learning curve, for without it standardization and outcomes of the main study would be compromised. J Am Diet Assoc. 1998;98:322–325.     

An evaluation of a rehabilitation workshop

Staff awareness of the steps involved in rehabilitation was assessed before and after a multidisciplinary workshop concerned with the aims, methods and principles of rehabilitation in psychiatry. Results were compared with similar assessments derived from a matched control group which was not exposed to any educational programme. The data suggest severe limitations in staff performance on the rehabilitation problem solving task which was used. Performance was not improved by the workshop, and the limitations of staff opinion as measures of the educational value of the workshop were clearly demonstrated. These results are consistent with other findings, and demonstrate the need to evaluate educational programmes provided in the Health Services.