An association between certain congenital abnormalities and the malignant hyperthermia trait

Although an association between malignant hyperthermia (MH) and congenital abnormalities has been recorded, no prospective study has been attempted to investigate this relationship. Standardised in vitro muscle tests were performed, because of impending anaesthesia for corrective surgery, on 25 children with birth defects similar to those induced by hyperthermia in laboratory animals, and in whom excessive pyrexial reactivity to anaesthesia, drugs or stress were recorded. Fifteen of the 25 children were MH positive by responding abnormally to the administration of halothane/caffeine. Five of these patients reacted positively to both caffeine and halothane, while the remainder manifested a contractile response to halothane only. This study underlines the existence of an anaesthetic risk factor associated with certain congenital abnormalities and neurodevelopmental delay and emphasises the need for further research to elucidate the possible importance of heat stress during fetal development in genetically susceptible individuals.     

The antitumor effects of the quinoline-3-carboxamide linomide on Dunning R-3327 rat prostatic cancers.

Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxo-quinoline-3- carboxamide) is a quinoline 3-carboxamide which previously has been demonstrated to produce immunomodulator and antitumor effects when given in vivo. To test the possible antitumor effects of linomide against prostatic cancers, rats bearing five distinct Dunning R-3327 rat prostatic cancer sublines were treated daily with i.p. injections of linomide. These studies demonstrated that linomide has a reproducible antitumor effect against all of the prostatic cancers tested regardless of their growth rate, degree of morphologic differentiation, metastatic ability, or androgen responsiveness. This antitumor effect is observed only in vivo, not in vitro, and involves a cytotoxic response of the prostatic cancer cells. This cytotoxic response results in the retardation of the growth rate (i.e., increased tumor volume doubling time) of primary prostatic cancers and in metastatic lesions. Linomide's growth retardation is reversible, and thus continuous daily treatment with linomide is required for maximal antitumor response. Pretreatment of rats with linomide before tumor inoculation has no effect in addition to that produced by initiating linomide treatment at the time of tumor inoculation. No enhancement of either natural killer cell number or natural killer cell cytotoxic activity is induced by linomide treatment in the tumor-bearing rats. In addition, depletion of natural killer cell activity via injections of asialo-GM1 antiserum does not prevent the antitumor effects of linomide in vivo. Likewise, the antitumor effects of linomide are also produced in prostatic cancer-bearing athymic nude rats. These results suggest that the requirement for host involvement in the antitumor effects of linomide against rat prostatic cancers may involve both immune and nonimmune host mechanism(s) (e.g., antiangiogenesis).     

Cancer of the maxillary sinus treated with surgery and/or radiation therapy

This is an analysis of 37 previously untreated patients with squamous cell carcinoma of the maxillary sinus treated with curative intent at the University of Florida from January 1966 through January 1984. All patients were followed for at least two years and 86 per cent (32/27) were followed for a minimum of five years. Patients were treated for cure with radiation therapy alone (25), surgery alone (1), or surgery and preoperative (6) or postoperative (5) radiation therapy. This study presents the results of treatment and the incidence of treatment-related complications in this group of patients.     

Programmed death of nonproliferating androgen-independent prostatic cancer cells

Androgen ablation induces an energy-dependent process of programmed death in nonproliferating androgen-dependent prostatic cancer cells which involves fragmentation of genomic DNA into nucleosomal oligomers catalyzed by nuclear Ca2+, Mg(2+)-dependent endonuclease enzymes activated following a sustained elevation in intracellular free Ca2+ (Cai). In contrast, androgen-independent prostatic cancer cells are not induced to undergo such programmed cell death by androgen ablation. One explanation for the inability of androgen ablation to induce programmed death of androgen-independent prostatic cancer cells is that such ablation does not result in a sustained elevation in Cai in these cells. This raises the issue of whether androgen-independent prostatic cancer cells can be induced to undergo programmed death if an elevation in the Cai is sufficiently sustained by nonhormonal means. To test this possibility, androgen-independent, highly metastatic Dunning R-3327 AT-3 rat prostatic cancer cells were chronically exposed in vitro to the calcium ionophore ionomycin to sustain an elevation in their Cai. These studies demonstrated that an elevation of Cai as small as only 3-6-fold above baseline can induce the death of these cells if sustained for greater than 12 h. Temporal analysis demonstrated that the death of these cells does not require cell proliferation and involves Ca(2+)-induced fragmentation of genomic DNA into nucleosome-sized pieces as the commitment step in this process. These results demonstrate that even nonproliferating androgen-independent prostatic cancer cells can be induced to undergo programmed cell death if a modest elevation in the Cai is sustained for a sufficient time. These observations identify Cai as a potential target for therapy for androgen-independent prostatic cancer cells.     

Why do women doctors in the UK take hormone replacement therapy?

STUDY OBJECTIVES: To ascertain the determinants and experiences of hormone replacement therapy (HRT) use by menopausal women doctors. DESIGN: Postal questionnaire. SETTING: UK. PATIENTS: A randomized stratified sample of women doctors who obtained full registration between 1952 and 1976, taken from the current Principal List of the UK Medical Register. MAIN OUTCOME MEASURES: Current and previous use of HRT; reasons for and against HRT use; menopausal status; hormonal contraceptive use; lifestyle patterns; family and personal history of disease. MAIN RESULTS: While 73.2% of 471 users had started HRT for symptom relief, 60.9% cited prevention of osteoporosis and 32.7 prevention of cardiovascular disease. Altogether 18.7% had started for preventive purposes alone. Significant predisposing factors to starting HRT were the presence and severity of menopausal symptoms, surgical menopause, past use of hormonal contraception, and a family history of osteoporosis. HRT users were also more likely to use skimmed rather than full fat milk, to try to increase their intake of fruit, vegetables, and fibre, and to undertake vigorous physical activity at least once a week. They were less likely to have had breast cancer. Long duration users were more likely than short duration users to be past users of hormonal contraception and to be using HRT for prevention of osteoporosis as well as symptom relief; they were less likely to have experienced side effects. CONCLUSIONS: The high usage of HRT by women doctors reflects the fact that many started HRT on their own initiative and with long term prevention in mind. The results may become generalisable to the wider population as information on the potential benefits of HRT is disseminated and understood. However, HRT users may differ slightly from non-users in health-related behaviour and a substantial minority may never take up HRT, at least until the benefit-risk ratio is more clearly established.     

EMPHYSEMATOUS CHOLECYSTITIS CAN CAUSE PNEUMOPERITONEUM

A case of emphysematous cholecystitis with gall-bladder perforation, resulting in free intraperitoneal gas, is presented. It adds to only nine previous reports. A successful outcome was achieved by early surgery, combined with appropriate antibiotic therapy.     

Psychiatric morbidity in policemen and the effect of brief psychotherapeutic intervention — a pilot study

The level of psychiatric morbidity and perceived sources of stress among police officers were investigated using the General Health Questionnaire (GHQ) and a stress situation questionnaire, which were sent to 171 officers. Half of the responders were invited to attend group counselling sessions weekly for 12 weeks. Outcome measures studied were a second GHQ completed at the end of the treatment period and the amounts of sick leave taken in the 12-week period before, during and after the treatment period. The results were that 61 people returned the first GHQ of whom 59 were male and of whom 14 were classed as ‘cases’. Of the 31 assigned to the treatment group, 22 attended at least one session. Responses to the stress situation questionnaire and the content of counselling sessions tended to confirm the impression that internal aspects of the organization were viewed as prime sources of stress and dissatisfaction. There were no significant changes in GHQ score within or between groups, nor were there significant differences in the amount of sick leave taken. Nevertheless the sessions appeared to be valued and we conclude that this sort of intervention is at least feasible. We recommend that similar studies measure psychiatric morbidity during treatment and at follow-up, rather than immediately after finishing, when reactions to this termination are prominent.