First rotavirus vaccine licensed: Is there really a need?

The first rotavirus vaccine was licensed in the United States on 31 August 1998 for the prevention of severe rotavius diarrhea in children. Despite this landmark in new vaccines, many pediatricians and public health professionals in Europe are uncertain of the need for this vaccine for the routine immunization of infants. In Europe, ample evidence suggests that rotavirus is the most common cause of hospitalizations for severe diarrhea among children, but proper studies documenting the disease burden of rotavirus or th cost-effectiveness of a rotavirus immunization program have only been conducted in the United Kingdom following epidemiologic models used in the United States. All children are infected with rotavirus during their first few years of life, 30-50% of diarrheal hospitalizations among children <5 years are due to this agent, and, by the age of 5 years, between 1 in 40 and 1 in 77 children in Europe and the United States may be hospitalized for rotavirus. The first vaccine is a live, oral preparation combining four different serotypes of rotavirus and administered in three doses with other childhood immunizations. The good efficacy against severe rotavirus diarrhea, the low risk of adverse side effects and the positive costeffectiveness equation have led the two major immunization advisory groups in the U.S. to recommend this vaccine for routine use in American infants. European physicians and policymakers should re-examine the epidemiology and disease burden of rotavirus diarrhea now that an effective method of prevention is at hand. □ Childhood immunization, diseases, rotavirus, vaccination .     

A case of near‐drowning: a case for routine cerebral monitoring

A 6‐week‐old infant presenting with near‐drowning was medically paralysed and ventilated on admission. Status epilepticus was found on cerebral function monitoring, without which the diagnosis would have been missed or delayed for many hours. This case illustrates the value of cerebral function monitoring for patients in intensive care, where clinical signs of seizure activity are frequently masked by paralysis and sedation. Conclusion: Limited availability of electroencephalogram (EEG) and cerebral function monitoring (CFM) in paediatric intensive care may inadvertently delay diagnosis and appropriate treatments and so adversely affect outcomes. We propose that round‐the‐clock cerebral function and/or EEG monitoring should be available in all centres that provide paediatric intensive care.     

Losses disguised as wins in modern multi‐line video slot machines

Aims Players can wager on multiple lines of modern slot machines. When they spin and fail to gain any credits, the machine goes into a state of relative quiet. By contrast, when they spin and win, these spins are accompanied by reinforcing sights and sounds. Such reinforcement also occurs when the amount won is less than the spin wager. We sought to show that these ‘losses disguised as wins’, or LDWs, would be as arousing as wins, and more arousing than regular losses. Measurement and participants We measured skin conductance response (SCR) amplitudes and heart‐rate changes following wins, LDWs and losses for 40 novices playing a multi‐line slot machine. Findings SCR amplitudes were similar for wins and LDWs—both were significantly larger than for regular losses. Conclusions For novice players, the reinforcing sights and sounds of the slot machine triggered arousal on wins, where the number of credits gained was greater than the spin wager, but also on ‘losses disguised as wins’ where the amount ‘won’ was less than the spin wager. Despite the fact that players lost money on these spins, these outcomes were more arousing than regular losses where no credits were gained. Although these findings involve novice players, the heightened arousal associated with these losses may have implications for the development of problem gambling, as arousal has been viewed as a key reinforcer in gambling behaviour.     

A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition

Many drugs have been associated with QTc prolongation and, in some cases, this is augmented by concomitant administration with metabolic inhibitors. The effects of 6 antipsychotics on the QTc interval at and around the time of estimated peak plasma/serum concentrations in the absence and presence of metabolic inhibition were characterized in a prospective, randomized study in which patients with psychotic disorders reached steady-state on either haloperidol 15 mg/d (n = 27), thioridazine 300 mg/d (n = 30), ziprasidone 160 mg/d (n = 31), quetiapine 750 mg/d (n = 27), olanzapine 20 mg/d (n = 24), or risperidone 6-8 mg/d increased to 16 mg/d (n = 25/20). Electrocardiograms (ECGs) were done at estimated Cmax at steady-state on both antipsychotic monotherapy and after concomitant administration of appropriate cytochrome P-450 (CYP450) inhibitor(s). Mean QTc intervals did not exceed 500 milliseconds in any patient taking any of the antipsychotics studied, in the absence or presence of metabolic inhibition. The mean QTc interval change was greatest in the thioridazine group, both in the presence and absence of metabolic inhibition. The presence of metabolic inhibition did not significantly augment QTc prolongation associated with any agent. Each of the antipsychotics studied was associated with measurable QTc prolongation at steady-state peak plasma concentrations, which was not augmented by metabolic inhibition. The theoretical risk of cardiotoxicity associated with QTc prolongation should be balanced against the substantial clinical benefits associated with atypical antipsychotics and the likelihood of other toxicities.     

DNA adduct formation in precision-cut rat liver and lung slices exposed to benzo[a]pyrene.

Chemical-DNA adducts provide an integrated measure of exposure, absorption, bioactivation, detoxification, and DNA repair following exposure to a genotoxic agent. Benzo[a]pyrene (BaP), a prototypical polycyclic aromatic hydrocarbon (PAH), can be bioactivated by cytochrome P-450s (CYPs) and epoxide hydrolase to genotoxic metabolites which form covalent adducts with DNA. In this study, we utilized precision-cut rat liver and lung slices exposed to BaP to investigate tissue-specific differences in chemical absorption and formation of DNA adducts. To investigate the contribution of bioactivating CYPs (such as CYP1A1 and CYP1B1) on the formation of BaP-DNA adducts, animals were also pretreated in vivo with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) prior to in vitro incubation of tissue slices with BaP. Furthermore, the tissue distribution of BaP and BaP-DNA adduct levels from in vivo studies were compared with those from the in vitro tissue slice experiments. The results indicate a time- and concentration-dependent increase in tissue-associated BaP following exposure of rat liver and lung tissue slices to BaP in vitro, with generally higher levels of BaP retained in lung tissue. Furthermore, rat liver and lung slices metabolized BaP to reactive intermediates that formed covalent adducts with DNA. Total BaP-DNA adducts increased with concentration and incubation time. Adduct levels (fmol adduct/microg DNA) in lung slices were greater than liver at all doses. Liver slices contained one major and two minor adducts, while lung slices contained two major and 3 minor adducts. The tissue-specific qualitative profile of these adducts in tissue slices was similar to that observed from in vivo studies, further validating the use of this model. Pretreatment of animals with TCDD prior to in vitro incubation with BaP potentiated the levels of DNA adduct formation. TCDD pretreatment altered the adduct distribution in lung but not in liver slices. Together, the results suggest that tissue-specific qualitative and quantitative differences in BaP-DNA adducts could contribute to the lung being a target tissue for BaP carcinogenesis. Furthermore, the results validate the use of precision-cut tissue slices incubated in dynamic organ culture as a useful model for the study of chemical-DNA adduct formation.     

Evaluating the Impact of a School-based Prevention Program on Self-esteem,Body Image,and Risky Dieting Attitudes and Behaviors Among Kaua‘i Youth

Eating disorders and obesity (EDO) are increasing among youth, having serious long-term physical and psychological consequences. The purpose of this study was to determine if significant differences exist in EDO risk factors following participation of 4–6th grade students in a school-based EDO prevention curriculum. This community-based research project assessed students at baseline and one week following EDO intervention. Primary outcome variables measured self-esteem, body dissatisfaction, and high risk eating attitudes and behaviors. Pre and post-test differences were calculated using mixed models, correcting for clustering within schools and teachers. This study found mean changes in all scores in healthy directions, as well as movement of students into lower risk groups post-intervention. This program demonstrated that a classroom curriculum is associated with decreased risks of EDO in boys and girls, supporting prevention programs at an early age for both sexes. Studies to determine long term benefit and guide booster interventions are warranted.     

THE EFFECT OF PROSTAGLANDIN E1 ON PULMONARYBLOOD FLOW AFTER RETROGRADE FLUSH ANDCOLD STORAGE OF LUNGS

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Changes in lipids over twelve months after initiating protease inhibitor therapy among persons treated for HIV/AIDS

Background  

Protease inhibitors are known to alter the lipid profiles in subjects treated for HIV/AIDS. However, the magnitude of this effect on plasma lipoproteins and lipids has not been adequately quantified.