Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

Summary What is Known and objective Hot days are increasingly common and are often associated with increased morbidity and mortality, especially in the elderly. Most heat‐related illness and heat‐related deaths are preventable. Comment Medicines may accentuate the risk of dehydration and heat‐related illness, especially in elderly people taking multiple medicines, through the following mechanisms: diuresis and electrolyte imbalance, sedation and cognitive impairment, changed thermoregulation, reduced thirst recognition, reduced sweat production, and hypotension and reduced cardiac output. What is new and conclusion Commonly used medicines that may significantly increase the risk include diuretics, especially when combined with an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), anticholinergics and psychotropics. Initiation of individualized preventive measures prior to the start of the hot weather season, which includes a review of the patient and their medicines to identify thermoregulatory issues, may reduce the risk of heat‐related illness or death.

SUMMARY Four previously healthy children acquired skin problems that were treated with topical or intralesional fluorinated corticosteroids. Three developed signs that suggested Cushing's syndrome 1-4 months after initial treatment. Investigation showed low plasma cortisol levels and inadequate response to corticotrophin stimulation. After 7 months of treatment with topical steroids the fourth child presented with failure to thrive; during a febrile illness he had a convulsion followed by acute hypotension which responded to parenteral corticosteroid administration. Adrenal function was not studied in this patient. Although fluorinated corticosteroids seldom lead to overt adrenal suppression in children, they may impair pituitary-adrenal responses in some. Such patients should be given oral or parenteral steroid cover in the event of illness or trauma.

No abstract

SUMMARY 45 children were admitted to hospital after ingesting varying quantities of diphenoxylate (Lomotil). One died and 44 recovered without any sequelae. Four patients were comatose, 32 were drowsy, and 9 suffered respiratory depression. No correlation was found between ingested dose and the severity of symptoms. Because of its action in rendering the gut atonic, removal of diphenoxylate by gastric lavage is mandatory, even in patients admitted at least 24 hours after drug ingestion. Naloxone is the narcotic antagonist of choice, and should be used in all cases where suspected diphenoxylate poisoning leads to respiratory depression or coma.