Lung dose rate and interstitial pneumonitis in total body irradiation for bone marrow transplantation

The effect of dose rate to the lungs and development of interstitial pneumonitis (IP) was evaluated in 114 bone marrow transplant patients receiving fractionated total body irradiation (TBI) (1200 rads TD in 6 fractions twice daily over 3 days) as part of their pre-conditioning regimen. The tumour dose (TD) was calculated as the mean lung dose as previously described (1). A 6MV linear accelerator at a mid-line dose rate of 7.5 rads/minute was used between March 1981 and June 1985 and a Co-60 source at 5 rads/minute thereafter. This resulted in a range of dose rates to the lung of between 6.9 and 8.9 rads/minute and 2.9 and 6.5 rads/minute respectively. In the majority of patients the aetiology of IP was investigated by lung biopsy with histology and culture. There was no statistically significant difference in the incidence of IP over the two sets of dose rates. Our study suggests tat the incidence of IP using fractionated TBI is not influenced by dose rates below 8.9 rads per minute.     

Sickness Absence from Work and Influenza Immunization

The worth of influenza immunization for employees in U.K. industryhas been debated for more than a decade. In this study no evidencecould be found of a protective effect for sickness absence patterns.Other evidence is also cited that suggests routine influcnzalimmunization programmes for healthy adults of working age areno longer justilied. *Requests for reprints should be addressed to: Dr Robin Philipp, Department of Epidemiology and Community Medicine, University of Bristol, Bristol BS8 2PR.     

Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis

Inflammatory bowel disease is associated with mucosal neutrophil recruitment and activatation, mediated in part by arachidonic acid metabolites. G-CSF attenuates the immune response to sepsis and ameliorates glycogen storage disease Ib-related colitis. These actions may be effected through the shedding of neutrophil adhesion molecules, or inhibition of proinflammatory mediator synthesis. Immune complex colitis was used to evaluate the effect of rhG-CSF on colonic mucosal inflammation, neutrophil recruitment and the generation of eicosanoids. Immune complex colitis was induced in White New Zealand rabbits. Animals were pretreated with rhG-CSF either 24 h before induction, or at induction, with dosages of 50 and 200 μg/kg. rhG-CSF caused a time- and dose-dependent neutrophilia in all animals. Pretreatment with rhG-CSF resulted in increased tissue myeloperoxidase levels, despite a histologically similar mucosal polymorphonuclear cell infiltrate between treated and control colitis groups. Leukotriene B₄ (LTB₄) and thromboxane B₂ (TXB₂) dialysis fluid levels were lower in treated animals, in particular in the groups receiving two doses (LTB₄: both P < 0.01; TXB₂: both P < 0.01. Prostaglandin E₂ (PGE₂) levels in dialysis fluid of the rhG-CSF-treated animals showed no difference from controls. In this model of experimental colitis, high-dose therapy with G-CSF resulted in a marked decrease of proinflammatory mediators, but mucosal generation of the protective PGE₂ was preserved. These results suggest that prolonged high-dose therapy with G-CSF may have anti-inflammatory effects in colitis.     

Sensory Responses to Fat are Not Affected by Varying Dietary Energy Intake From Fat and Saturated Fat Over Ranges Common in the American Diet

Objective To examine the effects of manipulating dietary fat in foods on sensitivity and hedonic response to fat in selected foods.Design Twenty subjects were randomly assigned to a sequence of three 8-week experimental diets (average American diet, step 1 diet, low-saturated-fat diet) that varied in energy from fat (37%, 30%, and 26%, respectively) and saturated fat (17%, 10%, and 6%, respectively). Subjects participated in sensory tests designed to assess their sensitivity to and liking for fat in several foods, before the study (baseline), after consumption of each diet, and after the study (washout).Subjects/setting Subjects were participants in the Dietary Effects on Lipoprotein and Thrombogenic Activity (DELTA) study.Results No significant differences were found among diets for difference thresholds (ie, just noticeable differences) for fat in milk and pudding, ad libitum mixing of low- and high-fat samples of milk and soup, and hedonic scaling of fat concentrations in milk and muffins and of cheese, mayonnaise, hot dog, and pastry samples.Applications/conclusions Within the dietary fat ranges and for the fat stimuli tested in this study, dietary fat as percentage of energy from fat and saturated fat was not a significant determinant of sensitivity to and/or liking for fat. Sensory factors should not be a barrier to the implementation of low-fat diets such as the step 1 and low-saturated-fat diets. J Am Diet Assoc. 1999;99:690–696.     

Salivary gland botulinum toxin injections for drooling in children with cerebral palsy and neurodevelopmental disability: a systematic review

Aim The aim of this paper was to systematically review the efficacy and safety of botulinum toxin (BoNT) injections to the salivary glands to treat drooling in children with cerebral palsy and neurodevelopmental disability. Method A systematic search of The Cochrane Central Register of Controlled Trials, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and the Physiotherapy Evidence Database (PEDro) was conducted (up to 1 October 2011). Data sources included published randomized controlled trials (RCTs) and prospective studies. Results Sixteen studies met inclusion criteria. Three outcome measures support the effectiveness of BoNT for drooling. One RCT found an almost 30% reduction in the impact of drooling on patients’ lives, as measured by the Drooling Impact Scale (mean difference ?27.45; 95% confidence interval [CI] ?35.28 to ?19.62). There were sufficient data to pool results on one outcome measure, the Drooling Frequency and Severity Scale, which supports this result (mean difference ?2.71; 95% CI ?4.82 to ?0.60; p<0.001). There was a significant reduction in the observed number of bibs required per day. The incidence of adverse events ranged from 2 to 41%, but was inconsistently reported. One trial was terminated early because of adverse events. Interpretation BoNT is an effective, temporary treatment for sialorrhoea in children with cerebral palsy. Benefits need to be weighed against the potential for serious adverse events. More studies are needed to address the safety of BoNT and to compare BoNT with other treatment options for drooling.     

Mechanism-Specific Antiarrhythmic Effects of the Potassium Channel Activator Levcromakalim Against Repolarization-Dependent Tachycardias

Mechanism-Specific Action of Levcromakalim. Introduction: The hypothesis that levcromakalim. a potassium channel (I_K-ATP.) activator with antihypertensive properties, has a mechanism-specific antiarrhythmic action against repolarization-dependent ventricular tachycardias (VTs) was tested in dogs. Methods and Results: A low dose of leveromakalim (0.01 mg/kg) was selected, which decreased blood pressure by 25% but had almost no electrophysiologic effect on AV nodal or ventricular conduction or effective refractory period. In dogs with chronic AV block, the antiarrhythmic action of this dose of levcromakalim was evaluated in three models of abnormal impulse formation: (I) dsotalol (2 mg/kg) induced torsades de pointes VT, initiated by early afterdepolarizations (EADs). (2) sustained ouabain-induced VTs, which are dependent on delayed after depolarizations (DADs), and (3) VT occurring 24 hours after left anterior descending coronary artery occlusion, which are likely based on abnormal automaticity. Levcromakalim abolished d-sotalol induced U waves, ventricular ectopic beats, and self-terminating bouts of torsades de pointes. Induction of torsades de pointes by pacing was also completely prevented. The cycle length of the idioventricular rhythm, which was lengthened after d-sotalol from 1490 ± 515 to 1700 ± 610 msec (P < 0.05), remained similar after levcromakalim (1655 ± 580 msec). The QT(U) duration, which was increased after d-sotalol from 410 ± 55 to 550 ± 40 msec (P < 0.05), normalized to 405 ± 70 msec (P < 0.05). Lcvcromakulim did not suppress but rather enhanced ouabain-induced VT by decreasing the cycle length slightly from 315 ± 35 to 290 ± 35 msec (P < 0.05). Pretreatment with a beta Mocker prevented this acceleration in rate. Finally, levcromakalim had no effect on VT 24 hours after infarction. Conclusion: A low dose of levcromakalim has specific antiarrhythmic properties against repolarization-dependent arrhythmias, but it does not affect VTs based on other mechanisms of abnormal impulse formation.     

CARBAMAZEPINE USE IN AGGRESSIVE BEHAVIOUR ASSOCIATED WITH SENILE DEMENTIA

In a randomized placebo crossover controlled study, six patients meeting DSM-III-R criteria for Alzheimer's disease and exhibiting significantly aggressive behaviour were administered carbamazepine (in doses up to 600 mg daily) and placebo, with each treatment period lasting 8 weeks. Levels of aggression as measured by the RAGE scale were significantly reduced compared with placebo (p<0.05). The results suggest that carbamazepine is an effective anti-aggressive agent in patients with dementia. Recommendations for further studies are made.