Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder (aswpd), delayed sleep-wake phase disorder (dswpd), non-24-hour sleep-wake rhythm disorder (n24swd), and irregular sleep-wake rhythm disorder (iswrd): an update for 2015

A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/ adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second- and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/ populations, due to either insufficient or absent data. Areas where further research is needed are discussed.

Preponderance of hypokalaemia as a cause of acute onset quadriparesis in northern India/southern Nepal.

Of 68 patients who were admitted with acute quadriparesis to a hospital in northern India, over 70% were found to be hypokalaemic. The most common cause of hypokalaemia was that associated with gastroenteritis (54%). These patients had all received intravenous fluids previously. It is likely that their hypokalaemia was caused by gastrointestinal loss compounded by parenteral fluid replacement. The next most common group of hypokalaemia-associated quadriparesis had no obvious cause for hypokalaemia (38%). Hypokalaemia-induced quadriparesis is a potentially life-threatening illness which can be readily treated with potassium supplements. The physician should consider hypokalaemia in patients who present with acute onset quadriparesis, and even if diagnostic tests for hypokalaemia are not available, should consider a judicious trial of potassium supplementation empirically, provided that there are no contraindications.

Evaluation of transcriptional fusions with green fluorescent protein versus luciferase as reporters in bacterial mutagenicity tests.

A bacterial plasmid was constructed on which the regulatory region of the umuC gene of Escherichia coli was fused to the coding sequence of the green fluorescent protein gene (gfp) from the jellyfish Aequorea victoria. Escherichia coli AB1157 strains carrying the plasmid emitted fluorescence in the presence of mutagens that induce the SOS DNA repair system. Data on tests with nitrosoguanidine, methylmethane sulphonate and UV radiation (254 nm) are presented. Although fluorescent detection using this system was not as rapid or sensitive as a similar luminescent equivalent (umuC-luxAB), the gfp reporter system was more robust. Escherichia coli umu gene induction was also analysed in Salmonella typhimurium TA1537 cells following plasmid transfer and exposure to the same range of mutagens. There was no significant difference in sensitivity between the two species. These preliminary results will provide the basis for development of mutagenicity test systems useful in the testing of complex mixtures, such as environmental samples, and the investigation of physiological parameters influencing spontaneous mutagenesis in bacteria.

Effect of high-dose verapamil administration on the Ca2+ channel density in rat cardiac tissue.

It is well known that beta-adrenergic receptors will down-regulate in the presence of high circulating levels of beta-adrenergic agonists over extended periods of time. However, less is known with respect to the effect of Ca2+ channel antagonist on their receptors. The purpose of this study was to determine if chronic administration of high dosages of verapamil (in the toxic range) could alter the density of Ca2+ channels in the heart as determined by [3H]PN 200-110 binding. A range of high verapamil concentrations was administered to rats via s.c. implantable slow-release pellets or s.c. injection. An increasing rate of mortality was observed as the dose of verapamil administered increased. Quantitation of serum verapamil concentrations demonstrated that the s.c. slow release implantable pellets were not releasing the drug evenly and instead released toxic quantities of drug during the first 24 h after implantation. Serum verapamil levels determined from verapamil-injected animals demonstrated a dose-dependent increase in circulating levels. No significant alterations in Ca2+ channel characteristics (Bmax and Kd) were noted in cardiac tissue obtained from either treatment regime. Our results demonstrate that implantable pellets are not a reliable administration method for verapamil and cardiac Ca2+ channels are unusually resistant to biochemical alterations even after administration of verapamil dosages in the toxic range.

Metronidazole prevention of serum liver enzyme abnormalities during total parenteral nutrition.

Abnormal serum liver enzymes are common in adults receiving total parenteral nutrition (TPN). The mechanism(s) responsible for these changes is unclear. One hypothesis is that there is overgrowth of intestinal anaerobic bacteria with subsequent toxic effects on the liver from endotoxins and/or bile acids. A retrospective survey of patients receiving TPN was undertaken. The patients were divided into two matched groups. One group had received metronidazole, a drug that suppresses anaerobic bacteria, while the other group had not. The administration of metronidazole during TPN was associated with prevention of the expected rise of serum alkaline phosphatase, gamma glutamyl transpeptidase, and aspartate amino-transferase. This study supports the concept that anerobic intestinal bacteria may be involved in the pathogenesis of liver changes commonly observed during TPN.