Incretins: a new treatment option for type 2 diabetes?

This article describes how the discovery of a protein almost 100 years ago led to a clinical treatment for type 2 diabetes. Food intake, but also stimulation of the sympathetic nervous system (for example physical exercise), stimulates the secretion of glucagon-like-peptide-1 (GLP-1), derived from the glucagon precursor proglucagon in the small intestine. GLP-1 stimulates the production and secretion of insulin, the release of somatostatin, glucose utilisation by increasing insulin sensitivity and in animal studies also beta-cell function and expansion (proliferation). It inhibits glucagon release, gastric emptying, appetite and food intake via the central nervous system and in animal experiments also apoptosis of beta-cells. Since GLP-1 has to be administered parenterally and its half-life is short, a long-acting GLP-1 receptor agonist (exenatide) and a long-acting GLP-1 analogue (liraglutide) have been developed as well as an inhibitor of DPP-IV (the enzyme that breaks down endogenous GLP-1). Clinical studies with exenatide and liraglutide as monotherapy show a significant increase in the postprandial insulin concentration as well as a smaller increase in the postprandial glucose values. Adding these drugs to standard oral glucose-lowering medication shows improvement in glucose and insulin concentrations and HbA1c compared with adding placebo. The effect of exenatide on HbA1c is the same as adding a long-acting insulin analogue (glargine), but the increase in weight after adding insulin is not seen after exenatide, where even a small decrease in weight is found. This is an important advantage, because most type 2 patients are already obese. Whether less beta-cell apoptosis and maintenance of beta-cell function occurs, as has been shown in animal studies, has to be awaited. Clinical studies with the oral DPPIV inhibitors sitagliptin and vildagliptin show promising results, but are only published as abstracts at scientific meetings.     

Transvaginal rectal repair: a new treatment option for symptomatic rectocele?

Purpose  

Widely differing surgical methods have been propagated to correct symptomatic rectocele. With transvaginal rectal repair (TVRR), we evaluate a method to reestablish the continuity of the rectal muscle wall, strengthen the weakened tunica muscularis, and restore normal rectal capacity and function.     

Bariatric embolization: a new and effective option for the obese patient?

Introduction: Obesity is a public health epidemic in the United States, which results in significant morbidity, mortality, and cost to the healthcare system. Despite advancements in traditional therapeutic options for the obese patients, there is a treatment gap for patients in whom lifestyle modifications alone have not been successful, but for whom bariatric surgery is not a suitable option.

Areas covered: This treatment gap needs to be addressed and thus, complimentary or alternative treatments to lifestyle changes and surgery are urgently needed. Recent evidence suggests that embolization of the gastric fundus (‘Bariatric Embolization’), which is predominantly supplied by the left gastric artery, may affect energy homeostasis by decreasing ghrelin production. The purpose of this special report is to discuss the background, rationale and latest data on this topic, as well as provide the latest data from the ongoing BEAT Obesity clinical trial.

Expert commentary: A multipronged approach is essential in the treatment of obesity. Bariatric embolization looks to treat the hormonal imbalances which contribute to obesity. If proven successful in the long-term, bariatric embolization represents a potential minimally invasive approach to treat obesity offered by interventional radiologists.     

Stroke prevention: what's new?

Abstract
Antithrombotic treatment has now been joined by other evidence-based drug interventions for pre­vention of stroke, including angiotensin-converting enzyme inhibitors and hydroxymethylglutaryl-CoA reductase inhibitors. The efficacy of oral anticoagulation in atrial fibrillation has not been seen in other stroke-prone groups, although trials are continuing. Diffusion-weighted magnetic resonance imaging improves diagnostic accuracy in acute stroke, which is important in arriving at the right secondary pre­vention strategy. Carotid endarterectomy has been shown to be beneficial for 50−69% symptomatic ­stenosis but with a much narrower therapeutic index than for 70−99% stenosis. A comparison of endarter­ectomy with angioplasty and/or stent placement has been the subject of one small trial suggesting similar procedural stroke and mortality risks. Device closure of cardiac abnormalities increases in the absence of any trial data, and in spite of a low subsequent stroke risk for young patients with isolated patent foramen ovale treated with aspirin. (Intern Med J 2003; 33: 177−181)     

Are cannabinoids a new treatment option for pain in patients with fibromyalgia?

Preliminary studies suggest that the synthetic cannabinoid nabilone might be an effective therapy in patients with fibromyalgia. Skrabek et al. performed a double-blind, randomized, placebo-controlled clinical trial to analyze the effects of nabilone on pain and quality of life in patients with fibromyalgia. After 4 weeks of treatment (0.5 mg once daily in week 1, 0.5 mg twice daily in week 2, 0.5 mg in the morning and 1 mg in the evening in week 3, and 1 mg twice daily in week 4), patients who received nabilone (n = 15) experienced significant improvements in clinical pain, measured on a visual analog scale (P <0.02), Fibromyalgia Impact Questionnaire score (P <0.02) and the 10-point anxiety scale of the Fibromyalgia Impact Questionnaire (P <0.02). After a 4-week wash-out period at the end of the trial, all benefits were lost in the nabilone cohort, which returned to their baseline levels of pain and quality of life. Patients who received placebo (n = 18) experienced no change throughout the study. Although nabilone was not associated with serious adverse effects, some patients did experience drowsiness, dry mouth, vertigo and ataxia as a result of treatment.     

Statins: a treatment option for chronic heart failure?

Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, consistently reduce cardiovascular risk. It has recently emerged that cholesterol reduction is not their only mode of action, with current research largely focused on the pleiotropic effects of statins. These include the improvement of endothelial dysfunction, their anti-inflammatory properties, and the mobilization of bone marrow-derived endothelial progenitor cells. All these effects are potentially beneficial in chronic heart failure (CHF), although prospective trials are needed to confirm this. However, cholesterol reduction by statins per se may prove detrimental in patients with CHF, as cholesterol seems to be able to inactivate endotoxin as a stimulus for proinflammatory cytokine production. It is therefore tempting to speculate that low doses of statins still confer pleiotropic effects without lowering plasma cholesterol levels.     

Treatment of sexually transmitted infections for HIV prevention: end of the road or new beginning?

Observational and biological data provide compelling evidence of the importance of sexually transmitted infections (STIs) in HIV transmission, but only one of nine intervention trials has shown an effect. This article reviews the observational studies, critically examines the nine randomized controlled trials evaluating the impact of STI treatment interventions on HIV incidence, and discusses implications for HIV prevention policy, programs and future research. The role of other vaginal infections is also briefly considered. In aggregate, the evidence strongly supports the concept that STI treatment prevents HIV infection. However, issues in trial design and conduct, including HIV epidemic phase, STI prevalence, intervention in comparison groups, and power have affected five of the six trials of treatment of curable STIs. In the three herpes intervention trials, antivirals for HSV suppression were insufficiently potent to alleviate persistent genital inflammation in HIV-negative HSV2-positive persons, and the reduction in HIV levels in HIV-positive persons was insufficient to reduce HIV transmission. It is time for a new phase of exploration of how, when, and in whom to include STI control as a key component of HIV prevention, driven by basic research to elucidate the mechanisms by which STIs and vaginal infections facilitate HIV transmission. From a policy perspective, treatment of curable STIs is an essential part of primary healthcare and is a cheap, simple, and effective intervention when appropriately targeted and delivered. It should be promoted as an essential component of HIV control programs in communities in which the burden of STIs is substantial.     

Split liver transplantation for acute Wilson's disease: new option for urgent recipient?

Wilson's disease is a rare metabolic disorder that may lead to fulminant hepatitis and subsequent liver failure. Herein, we present a case of split liver transplantation performed on a patient with acute Wilson's disease. A 27-year-old female with acute presentation of Wilson's disease and advanced neurological impairment, received a Right Split liver Graft (Segments: IV, V, VI, VII and VIII) transplant. The graft was obtained by an in situ splitting technique. The graft implantation was performed in a standard fashion. No acute rejection episodes of the organ occurred. The postoperative course was uneventful. The graft function, ceruloplasmine level and copper levels progressively normalized. The patient totally recovered from neurological symptoms and the Kayser-Fleischer rings disappeared within one month. At 13 months of follow-up, the patient presented with no symptoms and in good condition. The current literature reports high preoperative mortality rate in patients that underwent partial liver graft for acute hepatic failure. However, our experience indicates that in situ split technique of liver may be a feasible and effective alternative to whole graft transplantation in urgent cases. Moreover, to our knowledge, this is the first successfully case of in situ split liver transplantation for acute Wilson's disease described in literature.