\u00a9 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To quantify the incidence of any reported adverse event in patients taking cephalosporins compared with placebo for any indication.
\n \n\n \n \nBackground. Reports of abnormalities of potassium-channel function in various cultured cells of Alzheimer's disease patients led us to attempt to characterise the pharmacological characteristics of the abnormal channel. Methods. We studied platelets from 14 patients with Alzheimer-type dementia and 14 non-demented controls matched for age and sex. The effects of specific inhibitors of K+ channels on the efflux of rubidium-86 ions, a radioactive analogue of K+, from the platelets were measured. Findings. Normal platelets contain three types of K+ channel, sensitive to the inhibitory actions of apamin (small-conductance calcium-dependent potassium channels), charybdotoxin (of less specificity, but probably intermediate-conductance calcium-dependent K+ channels), and \u03b1-dendrotoxin (voltage-sensitive K+ channels). However, 86Rb+ efflux from the platelets of patients with Alzheimer-type dementia was not inhibited by either apamin or charybdotoxin. By contrast, inhibition by \u03b1-dendrotoxin did occur. Interpretation. Our results suggest that calcium-dependent K+ channels in platelets are selectively impaired in Alzheimer's disease. A similar abnormality in neurons could contribute to the pathophysiology of the disorder.
\n \n\n \n \n\u00a9 2015 The Cochrane Collaboration. This is the protocol for a review and there is no abstract. The objectives are as follows: Our primary objective is to quantify the incidence of any reported adverse event in patients taking macrolide antibiotics compared to placebo for any indication. The adverse events will be handled separately as adverse reactions, adverse effects, serious adverse events or subsequent carriage of resistant bacteria. Our secondary objective is to quantify the overall incidence of any reported adverse events in patients taking macrolide antibiotics compared to placebo.
\n \n\n \n \nOBJECTIVE: To review the beneficial and harmful effects of laughter. DESIGN: Narrative synthesis. DATA SOURCES AND REVIEW METHODS: We searched Medline (1946 to June 2013) and Embase (1974 to June 2013) for reports of benefits or harms from laughter in humans, and counted the number of papers in each category. RESULTS: Benefits of laughter include reduced anger, anxiety, depression, and stress; reduced tension (psychological and cardiovascular); increased pain threshold; reduced risk of myocardial infarction (presumably requiring hearty laughter); improved lung function; increased energy expenditure; and reduced blood glucose concentration. However, laughter is no joke-dangers include syncope, cardiac and oesophageal rupture, and protrusion of abdominal hernias (from side splitting laughter or laughing fit to burst), asthma attacks, interlobular emphysema, cataplexy, headaches, jaw dislocation, and stress incontinence (from laughing like a drain). Infectious laughter can disseminate real infection, which is potentially preventable by laughing up your sleeve. As a side effect of our search for side effects, we also list pathological causes of laughter, among them epilepsy (gelastic seizures), cerebral tumours, Angelman's syndrome, strokes, multiple sclerosis, and amyotrophic lateral sclerosis or motor neuron disease. CONCLUSIONS: Laughter is not purely beneficial. The harms it can cause are immediate and dose related, the risks being highest for Homeric (uncontrollable) laughter. The benefit-harm balance is probably favourable. It remains to be seen whether sick jokes make you ill or jokes in bad taste cause dysgeusia, and whether our views on comedians stand up to further scrutiny.
\n \n\n \n \nObjective: To determine whether anecdotal reports of suspected adverse drug reactions are valuable early warning signals. Design: Systematic literature survey. Data sources: We evaluated all case reports of adverse drug reactions published in 1997 in five medical journals. Reports were excluded if the adverse reaction had previously been described in earlier publications and was already listed in the product information of the drug reference source (the British National Formulary (BNF) or the Medicines Compendium). We used the Web of Knowledge Citation Index and Medline for 2003 to identify follow-up studies. Main outcome measures: Primary: the number of suspected adverse reactions subjected to formal validation studies and the findings of these studies. Secondary: the number of instances in which the warning from the case report was incorporated into the product information. Results: We evaluated 63 suspected adverse reactions and found that most (52/63, 83%) had not yet been subjected to further detailed evaluation. Data from controlled studies that supported the postulated link between the drug and the adverse event were available in only three cases. Of the 48 agents listed in the drug reference sources, details of the suspected reaction were subsequently added to the Medicines Compendium in 15 instances, and to the BNF in seven instances. In each case, only one reaction had been confirmed. Conclusions: Published case reports of suspected adverse reactions are of limited value as suspicions are seldom subjected to confirmatory investigation. Furthermore, these alerts are not incorporated into drug reference sources in a systematic manner.
\n \n\n \n \nWe have studied the in vivo response of the Na+/H+ antiporter in skeletal muscle to beta 2-adrenoceptor stimulation with isoprenaline and the effect of blocking L-type calcium channels with nifedipine. Na+/H+ antiporter activity in skeletal muscle in vivo increased after beta 2-adrenoceptor stimulation with isoprenaline; nifedipine attenuated that effect. This suggests that opening of L-type calcium channels is necessary for full activation of the Na+/H+ antiporter in skeletal muscle. Bleeding also increased Na/H+ antiporter activity, which we believe could be explained by an increase in sympathetic nervous system activity as a result of hypotension. This may be one of the mechanisms by which animals under stress prepare their skeletal muscle for exercise as part of the 'fright and flight' reaction.
\n \n\n \n \n\u00a9 2016 The Author(s). Inhibition of the H+/K+-adenosine triphosphatase (the proton pump) is the final common mechanistic pathway in reducing gastric acid secretion pharmacologically. Proton pump inhibitors are widely used in upper gastrointestinal diseases, including gastric and duodenal ulcers, eradication of Helicobacter pylori in combination with antibiotics, gastroesophageal reflux disease, Zollinger-Ellison syndrome, eosinophilic esophagitis, and prevention of non-steroidal anti-inflammatory drug-induced peptic ulceration. Reviewing their benefits and harms in BMC Medicine, Scarpignato et al. report effectiveness in these conditions, and harms that are generally mild and uncommon (1-3 %). Serious adverse reactions, such as tubulointerstitial nephritis, are rare. However, the risks of gastric and pancreatic cancer are unclear. Drug-drug interactions can occur through effects on P glycoprotein and cytochrome P450 (CYP) isoenzymes. Several questions remain. Do all proton pump inhibitors carry the same risks of serious adverse reactions? Which individuals are most susceptible? What are the time courses of individual reactions? What monitoring strategies are best? New drugs for the same indications continue to emerge, including potassium-competitive acid blockers, inhibitors of transient lower esophageal sphincter relaxation, serotonergic agents/prokinetics, mucosal protectants, histamine H3 receptor agonists, anti-gastrin agents, and esophageal pain modulators. Their benefit to harm balance remains to be discovered. Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0718-z
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