Myositis and swollen knees: disease or treatment complication?

Interesting and unusual causes of knee pain in three patients with idiopathic inflammmatory myositis seen in the clinic over the past 12 months are reported. Their clinical features are described and treatment discussed emphasising the importance of being able to differentiate between a manifestation of the rheumatic disease and a treatment complication. Publications on this topic are also reviewed.     

Editorial: fecal granins in IBS: cause or indicator of intestinal or colonic irritation?

Ohman et al. report increased fecal granins in patients with irritable bowel syndrome (IBS). Several interesting questions arise from their observations. Are the granins a cause of the pathophysiology or phenotype in IBS? Is the elevation of granins specific to IBS? What is the cause of increased fecal granin levels? Can fecal granin levels be used to diagnose IBS? Are increased fecal granins an expression of intestinal or colonic irritation? This paper adds to the body of evidence suggesting there are gastrointestinal disturbances in IBS; understanding these disturbances may provide clues to its pathogenesis and optimize management.     

Gut microbiota modulation: probiotics,antibiotics or fecal microbiota transplantation?

Gut microbiota is known to have a relevant role in our health, and is also related to both gastrointestinal and extradigestive diseases. Therefore, restoring the alteration of gut microbiota represents an outstanding clinical target for the treatment of gut microbiota-related diseases. The modulation of gut microbiota is perhaps an ancestral, innate concept for human beings. At this time, the restoration of gut microbiota impairment is a well-established concept in mainstream medicine, and several therapeutic approaches have been developed in this regard. Antibiotics, prebiotics and probiotics are the best known and commercially available options to overcome gastrointestinal dysbiosis. Fecal microbiota transplantation is an old procedure that has recently become popular again. It has shown a clear effectiveness in the treatment of C. difficile infection, and now represents a cutting-edge option for the restoration of gut microbiota. Nevertheless, such weapons should be used with caution. Antibiotics can indeed harm and alter gut microbiota composition. Probiotics, instead, are not at all the same thing, and thinking in terms of different strains is probably the only way to improve clinical outcomes. Moreover, fecal microbiota transplantation has shown promising results, but stronger proofs are needed. Considerable efforts are needed to increase our knowledge in the field of gut microbiota, especially with regard to the future use in its modulation for therapeutic purposes.     

Overestimation of peer drinking: error of judgement or methodological artefact?

Aims To examine whether inclusion of both self‐ and peer‐referent items in the context of a single social norms drinking questionnaire plays an active role in producing the much‐reported tendency for young people to overestimate the extent of peers' alcohol‐related behaviour and the permissiveness of their attitudes towards alcohol. Design, setting, participants and measurements In a between‐subjects design pupils attending two Scottish secondary schools (n = 1074; 12–18 years; 52.5% male) completed one of three questionnaires designed to measure a range of alcohol‐related behaviours, attitudes and perceptions: a paradigmatic multiple‐target questionnaire included self‐ and peer‐referent items while two single‐target questionnaires included self‐referent or peer‐referent items only. Findings Pupils' self‐reported drinking behaviours and attitudes were similar, regardless of whether multiple or single‐target versions of the questionnaire were used, as were perceptions of peers' frequencies of alcohol use and drunkenness. In contrast, by comparison with pupils who responded to a single‐target version that omitted self‐referent items, use of a multiple‐target questionnaire was significantly more likely to result in reports that peers would consume alcoholic drinks when with friends and hold more permissive or liberal attitudes towards alcohol. Conclusions Social norms research and related health promotion programmes that seek to reduce the extent of overestimation of peer drinking norms are heavily reliant upon multiple‐target drinking questionnaires. The use of such a questionnaire may lead to more distorted or extreme perceptions being reported by pupils compared to single‐target versions, which omit self‐referent drinking items. By implication, use of multiple‐target questionnaires may encourage young people to ‘over‐overestimate’ peer drinking norms.     

Difficulties in classifying a/g recombinants: methodological problems or genetic variability?

Thirty pol gene plasma-derived sequences clustering with the circulating recombinant form (CRF) 02_AG (IbNG) (bootstrap 100%) were evaluated to analyze the genomic composition. Subtype assignment was also phylogenetically confirmed by C2-V3 region analysis for 18/21 sequences evaluated. Thereafter, we compared the genomic recombination of the CRF02_AG/IbNG prototype as predicted by bootscanning and Jumping HMMER software (jpHMM) to that of our strains. With these methods, 27% and 50%, respectively, of our clinical sequences demonstrated the same pol structure as the prototype CRF02_A/G-IbNG. However, in subtrees built for each segment predicted by jpHMM (with a bootstrap value of more than 75%), all fragments clustered with IbNG and were distinct from A and G clades. Overall, our sequences resulted in true members of CRF02_AG-IbNG, which, however, appeared to be a subtype phylogenetically separate from A or G, at least with regard to the pol gene.     

Depression in chronic heart failure: complication, risk factor or autonomous disease?

A major depressive episode is diagnosed based on several well-defined criteria as the presence of depressed mood and loss of interest. According to a large meta-analysis the prevalence of major depression in patients with chronic heart failure is more than 20%. Etiological factors include individual (genetic) disposition and social environment as well as psychosocial stress and biological risk factors related to the chronic cardiac illness. As in coronary artery disease, mortality rates are increased in patients suffering from heart failure and comorbid depression. Possible mechanisms mediating this relationship include both biological (e.g. severity of chronic heart failure, autonomic and immunological dysregulation, multiple comorbidities) and behavioral factors (health behavior, compliance with pharmacological and non-pharmacological therapy). Shared pathophysiological mechanisms as well as a common genetic disposition are also discussed. Simple screening instruments and effective treatment options (psychotherapy, selective serotonin re-uptake inhibitors) are available. However, at present evidence is lacking that beyond improvement of depression these strategies impact favorably on morbidity and mortality.     

Toxic oligomers and islet beta cell death: guilty by association or convicted by circumstantial evidence?

Type 2 diabetes is a progressive disease characterised by islet amyloid deposits in the majority of patients. Amyloid formation is considered a significant factor in deterioration of islet function and reduction in beta cell mass, and involves aggregation of monomers of the normally soluble beta cell peptide, human islet amyloid polypeptide (hIAPP) into oligomers, fibrils and, ultimately, mature amyloid deposits. Despite extensive in vitro studies, the process of hIAPP aggregation in vivo is poorly understood, though it is widely reported to promote cytotoxicity. Recently, studies have suggested that only the early stages of fibril assembly, and in particular small hIAPP oligomers, are responsible for beta cell cytotoxicity. This challenges the prior concept that newly formed fibrils and/or mature fibrillar amyloid are cytotoxic. Herein, evidence both for and against the toxic hIAPP oligomer hypothesis is presented; from this, it is apparent that what exactly causes beta cell death when hIAPP aggregates remains debatable. Moreover, substantially more work with more specific reagents and techniques than are currently available will be required to identify conclusively the toxic species resulting from hIAPP aggregation. Keeping an open mind on the nature of the cytotoxic insult has implications for therapeutic developments and clinical care in type 2 diabetes.     

Children's weights: guess or measure by tape?

Children's doses of drugs are prescribed according to bodyweight but in resource-poor countries weighing scales may be unavailable, inaccurate, or broken. We designed a length/weight tape for use in our community and found it reasonably accurate for weights of 4-16 kg and better than a clinician's guess.     

Insulinoma after streptozotocin therapy for metastatic gastrinoma: natural history or iatrogenic complication?

Islet cell carcinoma frequently produces more than one chemical product, although its clinical expression is usually restricted to a single hormone. We describe an unusual patient who presented with full-blown metastasizing gastrinoma. He was treated with cimetidine for five years and then streptozotocin therapy, which resulted in a regression in hepatomegaly and a fall in serum gastrin levels. Following one year's therapy with streptozotocin, he was admitted in hyperinsulinemic hypoglycemic stupor. This appears to be the first reported case of a "shift" from clinical gastrinoma to insulinoma possibly related to prolonged streptozotocin therapy.     

Postoperative diabetes insipidus: how to define and grade this complication?

Pituitary - Although transient diabetes insipidus (DI) is the most common complication of pituitary surgery, there is no consensus on its definition. Polyuria is the most overt symptoms of DI, but...