Acute Urinary Tract Toxicity of Tetraethylorthosilicate in Rats

Acute stomach, kidney, and bladder toxicity was evaluated inF344 rats after gastric gavage of tetraethylorthosilicate (TES)at daily doses of 0, 0.111, 0.223, and 0.333 g. Five rats ofeach sex at each dose were sacrificed after 1, 2, and 4 days.In TES-treated groups, silicate accumulated in the stomach glandsand the muscle layer of the forestomach and glandular stomach.Serum chemistries demonstrated acute onset of renal failure.In the kidneys, acute tubular necrosis, accumulation of silicates,and superficial necrotizing papillitis were observed. In therenal pelvis and bladder, there was urothelial simple hyperplasia,focal erosion of the mucosa, edema, and inflammation. Theseacute toxic changes were dose and time dependent, but significantsex differences were not observed. The microscopic changes inthe urothelium were similar to those observed following administrationof high doses of sodium saccharin to male rats in which urinarysilicate precipitate and crystals form.     

Health promotion and cost-effectiveness

Successful health promotion may save resources but this is notits main objective. Health promotion programmes which cost morethan they save may still be an economically efficient way ofreducing premature death and improving quality of life. Theprinciples of health economics emphasise how scarcity makesresource allocation choices inescapable. They highlight thefact that the benefits from health promotion are achieved atthe sacrifice of potentially achievable benefits elsewhere.The thinking of economics and the techniques of economic appraisalcan help to show how more efficient choices between health promotionand other health producing interventions, as well as choiceswithin health promotion, can be made. One major problem withapplying economic appraisal to health promotion is the way inwhich the technique reduces the value of future benefits toaccount for the lower value which society appears to place onfuture versus current benefits (and costs). Emphasising thepeace-of-mind benefits of health promotion, which arise immediatelyas a result of the knowledge that risks are reduced, is oneway of partly overcoming the accusation that economic appraisalsdiscriminate against health promotion in favour of treatmentand cure. A plea is made for greater use of economics in healthpromotion.     

Adenosine Deaminase and Thymocyte Maturation

The congenital absence of adenosine deaminase in humans results in severe combined immunodeficiency. To clarify the process whereby thymocytes are destroyed in the absence of adenosine deaminase activity, we induced a parallel condition in mice through the injection of an inhibitor of adenosine deaminase, deoxycoformycin. We have observed that deoxycoformycin, in addition to maintaining high levels of dATP in thymocytes, blocks the progression of thymocyte differentiation at two points. As a result of the first block, the cortex is depleted of immature cortical thymocytes while CD4+CD8+ thymocytes with functionally rearranged T-cell receptors survive. As a result of the second block, the CD4+CD8+ thymocytes are prevented from further differentiation to mature CD4+CD8- or CD4-CD8+ T lymphocytes and accumulate at the corticomedullar junction and in the medulla. These observations suggest that the maintenance of dNTP pools by adenosine deaminase is critical to at least two stages of thymocyte differentiation.     

The use of extracorporeal membrane oxygenation in a child with adult respiratory distress syndrome following post-obstruction pulmonary oedema

The use of extracorporeal membrane oxygenation (ECMO) for post-operative complications is not well described. ECMO, a partial venoarterial cardiopulmonary bypass, may permit the reversal of pulmonary insult from barotrauma and oxygen toxicity. This report concerns an 8-year-old girl who developed post-obstruction pulmonary oedema and adult respiratory distress syndrome (ARDS) after a general anaesthetic for an attempted aspiration of a peritonsillar abscess and demonstrates an effective use of this technique. In this patient, the extreme levels of ventilatory support required post-operatively caused haemodynamic instability and severe barotrauma. The institution of ECMO with accompanying decrease in ventilatory support resulted in rapid resolution of haemodynamic instability, hypoxia, and pulmonary pathology.     

AV Pacing and LV Performance

Five patients with impaired left ventricular function (LV) and implanted AV sequential pacemakers underwent serial radionuclide angiograms. The goal was a non-invasive evaluation of the rapid changes in left ventricular performance elicited by rate, pacing mode and AV interval manipulation. End diastolic volume, end systolic volume, stroke volume and cardiac output were increased by AV sequential pacing in comparison with ventricular pacing at 70 beats per minute. No significant change in ejection fraction and blood pressure were noted with changing AV sequential pacing rates at usual pacing rates. Our data suggest that a short A V interval (150 ms) improved LV performance more than a long AV interval (250 ms). A non-invasive technique to optimize left ventricular performance on an acute basis by varying heart rate, AV interval and pacing mode with the implanted AV sequential pacemaker is feasible and may be useful in selective clinical situations.     

CONTRASTING EFFECTS OF SUBCUTANEOUS PULSATILE GnRH THERAPY IN CONGENITAL ADRENAL HYPOPLASIA AND KALLMANN''S SYNDROME

A patient with congenital adrenal hypoplasia (AH) and hypogonadotrophic hypogonadism was treated with pulsatile subcutaneous GnRH therapy for 16 weeks in an attempt to induce puberty. No rise in serum LH or FSH concentrations occurred despite increasing doses of GnRH (2.8 micrograms/pulse-22.4 micrograms/pulse). In contrast a similar programme of therapy successfully initiated the biochemical changes of puberty in a patient with Kallmann's syndrome. Both patients before therapy had low basal serum LH and FSH concentrations with blunted LH and FSH responses to GnRH stimulation. After 1 week, serum LH and FSH rose into the normal adult range in the patient with Kallmann's syndrome. This study fails to confirm a previous report which suggested that intermittent low dose GnRH therapy may be of value in inducing puberty in AH. The reasons for the difference of pituitary responsiveness to GnRH in AH and Kallmann's syndrome are unclear at present.     

Evaluation of Lactobacillus Preparation on Enterotoxigenic E. Coli-induced Rabbit Ileal Loop Reactions

A commercially available lactobacillus-containing preparation has been used extensively in the treatment of diarrhea but few laboratory tests have been performed to determine the efficacy of this product. The rabbit ileal loop reaction was used here to determine the effect of the lactobacillus preparation and its ingredients on E. coli enterotoxin-induced loop fluid response. Enterotoxigenic E. coli cells grown overnight in shake cultures were washed and resuspended in saline to the original volume. They were then diluted in TSB suspensions of the lactobacillus preparation or its ingredients and injected into ileal loops. E. coli diluted in TSB served as positive controls. Fluid response was measured after 18 hours and the loop fluid ratio (LFR) (ml./cm.) of the lactobacillus preparations was compared to the positive controls. The positive controls always showed a high loop fluid ratio (> 1.1 ml./cm.) and negative saline controls showed no fluid response. The lactobacillus granules and tablets had low LFR's (0.08 and 0.05, respectively). Ingredients (whey, talc, sugar, evaporated milk, mineral oil) had variable LFR's (0.65, 0.78, 1.39, 1.46 and 1.54, respectively). Individual ingredients used to make this preparation show little antifluid response when used separately but the final product exhibits a significant antienterotoxin response.