Patients with manic depressive disorder (DSM-III-R bipolar disorder) have an abnormality of the Na+,K(+)-ATPase pumps in their lymphocytes: the pump numbers do not upregulate to stimulation with lithium and ethacrynate. We have now investigated the in vitro adaptive responses of lymphocyte Na+,K(+)-ATPase pumps in the first-degree unaffected relatives of patients with a clear history of manic depressive disorder. The lymphocytes of the healthy relatives upregulated their Na+,K(+)-ATPase pumps normally, suggesting that the abnormal response that we have previously observed in patients with the disorder reflects a complex relation between the biochemical phenotype and the development of clinical symptoms.
\n \n\n \n \nBackground: 'Preventability' is a crucial concept in the literature on adverse drug effects. However, a systematic review of the definitions of preventability of adverse drug effects has suggested that none fits all circumstances. Furthermore, when the reliability of these definitions has been examined they have been found to be imperfect. Objective: To propose and outline a method for determining the theoretical preventability of an adverse drug effect, based on frameworks for classifying adverse drug reactions - the EIDOS and DoTS methods. Methods: EIDOS is based on the mechanism of action of the drug. It observes that a drug (an Extrinsic species) causes an adverse effect by interacting with an Intrinsic species that is its target when the two are Distributed together, and that the resulting pathophysiological Outcome (the adverse effect) causes the Sequela (the adverse reaction). DoTS observes that the Dose-relatedness of the adverse effect compared with the beneficial effect is relevant (determining toxic, collateral, or hypersusceptibility effects), that adverse effects have Time-courses (varying from immediate to delayed), and that there are individual Susceptibility factors. Results and Discussion: We have elicited many published examples that show that each of these factors in the causation of an adverse drug effect can be adduced to assess its preventability. We have constructed a flowchart that illustrates how the processes can be logically analysed. Conclusions: This approach suggests methods for devising prospective preventive strategies and for deciding retrospectively whether an adverse reaction in an individual should have been prevented. \u00a9 2010 Adis Data Information BV. All rights reserved.
\n \n\n \n \n'Preventability' is a crucial concept in the literature on adverse drug reactions (ADRs). We have carried out a systematic review in order to identify and analyse the approaches used to define 'preventability' in relation to ADRs. We have restricted this investigation to definitions of preventability and have not dealt with other aspects. We searched MEDLINE (1963April 2009) and EMBASE (1980April 2009), without language restriction, for papers in which preventability of ADRs was likely to be defined.We found 234 papers, of which we retrieved 231. Of these, 172 either contained original definitions of preventability or referred to other papers in which preventability was defined. Forty contained no definition, and 19 were not relevant. In the 172 papers selected, we identified eight different general approaches to defining the preventability of ADRs: (1) analysis without explicit criteria; (2) assessment by consensus; (3) preventability linked to error; (4) preventability linked to standards of care; (5) preventability linked to medication-related factors; (6) preventability linked to information technology; (7) categorization of harmful treatments in explicit lists; and (8) a combination of more than one approach.These approaches rely on two general methods: the judgement of one or more investigators or the use of pre-defined explicit criteria; neither is satisfactory. Specific problems include the weakness of consensus as a method (since experts can agree and yet be wrong), inadequacy of definition of standards of care, and circularity in several definitions of preventability. Furthermore, attempts to list all preventable effects are bound to be incomplete and will not always apply to an individual case.We conclude that an approach based on analysis of the mechanisms of adverse reactions and their clinical features could be preferable; such an approach is described in a companion paper (Part II) in this issue of Drug Safety. \u00a9 2010 Adis Data Information BV. All rights reserved.
\n \n\n \n \n\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.
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