POSSIBLE INVOLVEMENT OF INOSITOL-LIPID METABOLISM IN MALIGNANT HYPERTHERMIA

-Adrenoceptor stimulation may induce malignant hyperthermia(MH) in vivo. Consequently, we have investigated the effectsof the -adrenoceptor agonist phenylephrine and, for comparison,the effects of the ß-adrenoceptor agonist isoproterenolon inositol-lipid metabolism of malignant hyperthermia susceptible(MHS) and healthy control (MHN) swine. The experiments wereperformed on electrically stimulated (frequency 0.2 Hz) trabeculaeisolated from the right ventricles of the hearts of MHS andMHN animals. After labelling with [³H] inositol for 6 h, differentinositol phosphates were measured by high pressure liquid chromatography,including inositol 1 - phosphate, inositol 1,4-bisphosphate,inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP₃)and inositol 1,3,4,5 - tetrakisphosphate. After stimulationwith isoproterenol, the inositol phosphate content did not increaseor vary between muscle from MHS and MHN animals. In contrast,all inositol phosphates increased after stimulation with phenylephrinein both muscle types, the effects being greater in MHS thanin MHN, especially as regards 1,4,5-IP₃ content. As 1,4,5-IP₃,a presumed second messenger, has been shown to mobilize intracellularcalcium, it is concluded that an enhanced -adrenergic responseis involved in the development of MH. ^*Address for correspondence: Abteilung für Anästhesiologie,Universitäts-Krankenhaus Eppendorf, Martinistrasse52, D-2000Hamburg 20, Germany. Presented in part at the 1989 Meeting of the European Academyof Anaesthesiology in Bonn.     

A variant of guided exposure to mourning for use with treatment resistant patients.

We report a variant of "guided exposure to mourning," designed for use with patients who have proved resistant to other treatments for unresolved, morbid grief. The work provides some indication as to when such behavioral techniques for resolution of morbid grief are likely to prove successful, and when not.     

Exceptional diabetic arthropathy of the foot (author's transl)]

The osteopathy of the foot is a rare complication of diabetes mellitus. It is seen in the distal parts mostly. The arthropathy ("Charcot-joint") is even more rare, and is regularly combined with a neuropathy. The roentgen signs of the "diabetic foot" are demonstrated, as there are osteoporosis, iuxta-articular cortical defects, osteolysis of the bone ends, bone destruction and reconstruction, periost reaction and sklerosis of the bone shafts.     

Radiographic findings after duodenal surgery (author's transl)]

A gastroduodenostomy as part of partial gastric resection may change function and morphology of the duodenum in a typical fashion. End to side anastomosis may produce a blind pouch. An end to end anastomosis may lead to postanastomotic dilatation, which may mimick a duodenal bulb (a so called "neo -- or pseudobulb"). Abnormal duodenal peristalsis with atony may follow vagotomy, pyloroplasty, gastroduodenostomy or excisional duodenal biopsy and may thus result in functional obstruction. A blind loop syndrome may develop after bypass procedures for duodenal stenosis.     

Influence of age and of desmotropic drugs on the step phenomenon observed in rat skin

Summary Comprehensive analysis of the mechanical properties of rat skin revealed the step phenomenon. This particular observation was made after constant strain rate (analysis of stress strain curves) as well as after constant load (creep experiments). Relative low extensions or low loads were necessary to provoke the steps. In most cases two, sometimes three steps were observed. The step phenomenon was found mainly in skin strips punched out perpendicularly to the body axis. Probably some bonds in the fibrous network are broken giving way to additional elongation whereafter stronger links take over the stress. Since earlier studies demonstrated a pronounced influence of age and of desmotropic drugs on mechanical properties at ultimate load, e.g., tensile strength, ultimate modulus of elasticity, and ultimate strain, also the step phenomenon was studied under these conditions. In stress-strain experiments most of the steps were found at the ages of 2 and 4 months. Total stress loss and total work loss due to the steps were the highest at the age of 4 months. If, however, these values were calculated as percentage of ultimate values, the highest figures were found in young animals. Elongation gain due to the steps also showed a maximum at time of maturation, e.g., 4 months. Similar findings were achieved in creep experiments at medium load (200 g). After treatment with prednisolone acetate more steps and after treatment with d-penicillamine fewer steps were observed. In stress-strain experiments total stress loss and total work loss due to steps were more than twice as high than controls after prednisolone treatment and only one half after d-penicillamine. If calculated as percentage of ultimate stress or percentage of work input, these changes disappeared because of similar changes at ultimate load. However, elongation gain due to steps, which was not significantly influenced by prednisolone acetate but significantly decreased by d-penicillamine, showed the same changes when calculated as percentage of ultimate strain. Under all conditions the step phenomenon mainly influenced the extension parameters. The data presented here confirm earlier observations that mechanical properties at low loads or low and medium extensions show at least to some extent a different pattern under the influence of maturation and age and after treatment with desmotropic drugs compared to the mechanical parameters at ultimate load.     

MAO inhibition and the effects of centrally administered LSD,serotonin, and 5-methoxytryptamine on the conditioned avoidance response in rats

Pretreatment with the MAO-inhibitors iproniazid, clorgyline, or deprenyl abolishes the effects of LSD on the conditioned avoidance response (CAR) in rats. The effects of serotonin (5-HT) and 5-methoxytryptamine (5-MT) are greatly potentiated by these substances. Brain levels of LSD are not affected by MAO inhibition whereas levels of 5-HT and 5-MT are significantly elevated. It is postulated that the decreased behavioral response to LSD is the result of MAO inhibitor-induced changes whereas the increased response of 5-HT and 5-MT results from increased brain levels of these compounds.     

In vitro germ cell models for the detection of fertility impairment

Pluripotent embryonic carcinoma cells and pluripotent embryonic stem cells established from undifferentiated cells of an early mouse embryo were investigated for induction of proliferation inhibition, sister chromatid exchanges (SCE) and single-strand breaks by treatment with various germ cell mutagens. The comparison of malignant cells with nonmalignant cells showed an increased sensitivity of nonmalignant cells independent of their state of differentiation. Mitomycin C (MMC) inhibited the proliferation of nonmalignant cells at a concentration of 10(-6) M but did not affect growth of the teratocarcinoma cell line P19. There were no differences between the investigated cell lines at a lower MMC concentration. At the concentration of 10(-6) M MMC the sister chromatid exchanges of P19 were enhanced up to 41 SCE per metaphase. Testing of another germ cell mutagen, ethylnitrosourea (ENU), gave similar results: a decreasing generation time of nonmalignant cell lines after treatment with 1 mM ENU and no effect on the teratocarcinoma cells. This concentration also induced a high number of SCE. Single-strand breaks could be produced by exposure to methanmethylsulphonate (MMS). 56.3% of embryonic stem cell DNA was passing through the filter after MMS treatment. In contrast to the embryonic stem cells, only 35.6% of teratocarcinoma DNA was affected.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.