Pro-inflammatory cytokines and their receptors in chronic heart failure: do they really matter?

The pathophysiological insights into the chronic heart failure (CHF) syndrome and, consequently, the management of patients with CHF have dramatically changed over the past few decades.Antagonists of the activated neurohormonal pathways are now a mainstay in the therapeutic arsenal. It seems, however, that a neurohormonal ceiling might have been reached. Other humoral mal-adaptations have recently gained importance. One of them is the presence of a low-grade inflammatory status characterising patients with moderate to severe CHF. The presence, both at tissue level and in the circulation, of increased levels of pro-inflammatory cytokines suggests that immune activation might be a relevant mechanism contributing to cardiac as well as peripheral manifestations of the disease. Whereas targeted anti-cytokine treatment has proven unsuccessful in the CHF population, the concept of immune modulation is still intensively studied.     

Does matching matter? Examining matches and mismatches between patient attributes and therapy techniques in alcoholism treatment

AIMS: This study assessed the predictive validity of the level of matching and mismatching between patients' personal attributes and aspects of outpatient psychotherapy they received. DESIGN AND PARTICIPANTS: On the basis of patient-by-treatment interactions observed for this sample in previous research, patients with alcohol abuse or dependence (n = 137) were designated retrospectively as being matched, unmatched or mismatched on each of four patient and treatment variable pairings. These pairings included (1) patient depressive symptoms and therapy emotion focus, (2) patient trait anger and therapy confrontation, (3) patient interpersonal reactance and therapy confrontation and (4) patient interpersonal reactance and therapy structure. MEASUREMENTS: Analyses of variance and logistic regression were used to assess the individual and additive effects of being matched and mismatched on the percentage of abstinent days (PDA) and recovery status in the year after treatment. FINDINGS: Being mismatched on any of the four patient-treatment pairings was a significant predictor of more frequent alcohol use post-treatment. Being matched on only two pairings predicted less frequent alcohol use, namely matches on therapy emotion focus with patient depressive symptoms and therapy structure with patient reactance. Matches appeared to optimize otherwise good outcomes, while mismatches had larger effect sizes and tended to predict relatively poor outcomes. The data supported the presence of an additive effect for mismatches on post-treatment PDA. The group with the most mismatches fared considerably worse than a group with fewer mismatches. Several matches and mismatches also predicted recovery status, with some support found for additive effects. CONCLUSIONS: Mismatches between patient attributes and treatment appear to have serious consequences, and this effect is magnified with multiple mismatches. Matches, on the other hand, while beneficial, may not be necessary to achieve good outcomes.     

Gastrointestinal endoscopy in children and adults: How do they differ?

Gastrointestinal endoscopy has grown dramatically over the past century, and with subsequent improvements in technology and anaesthesia, it has become a safe and useful tool for evaluation of GI pathology in children. There are substantial differences between paediatric and adult endoscopy beyond size, including: age-related patho-physiology and the different spectrum of diseases in children. Literature on endoscopic procedures in children is sparse but significant. The present review aims at describing the current knowledges on paediatric endoscopy practice and highlights the main areas of differences between paediatric and adult practice.     

New drugs for hypertension: What do they offer?

A new drug might make a positive contribution to existing therapies for hypertension by: 1) reducing blood pressure (BP) via a novel pharmacologic mechanism; 2) possessing pharmacologic or pharmacokinetic properties that make it superior to other members of its class; or 3) facilitating BP control in refractory patients. In this paper, we review four experimental agents that promise to advance therapeutics by one of these mechanisms. Aliskiren is the first in a new class of potent, orally effective renin inhibitors. Aliskiren produces dose-dependent BP reduction with few side effects and constitutes a novel pharmacologic approach to renin-angiotensin-aldosterone inhibition. Nebivolol is a third-generation, cardioselective β-blocker that produces vasodilation and improves endothelial function via the L-arginine/nitric oxide pathway. Clevidipine is an ultra-short-acting, vascular-selective, dihydropyridine calcium antagonist that is being developed for intravenous use in acute hospitalized patients. Darusentan is an endothelinA selective endothelin receptor antagonist that is effective in achieving BP control in a significant percentage of patients who remain uncontrolled despite treatment with three or more antihypertensive drugs.     

Antibiotics for inflammatory bowel disease: do they work?

A growing amount of evidence indicates that the intestinal flora plays a pathogenic role in inflammatory bowel disease (IBD): hence, the use of anti-bacterial agents as ancillary treatment in patients with ulcerative colitis, or Crohn's disease. While the results with anti-tubercular agents remain inconclusive, antibiotic treatment in IBD is usually carried out with either metronidazole or ciprofloxacin, or both. Controlled trials are scarce and, although both antibiotics appear to provide clinical benefit, definitive conclusions cannot be drawn and precise therapeutic guidelines cannot be suggested. The best results are achieved in the long-term treatment of Crohn's disease and in the management of pouchitis, or of perianal Crohn's disease. Long-term tolerability of antibiotic treatment may be poor due to the appearance of systemic side-effects. The use of non-absorbable anti-bacterial agents such as rifaximin deserves further investigation.     

Relationships between adipose tissues and brain: what do we learn from animal studies?

Over the last decades, more and more data supporting the importance of the relationships between the brain and adipose tissues (white and brown) in regards of body weight regulation and energy homeostasis have been published. Indeed the brain via the autonomic nervous system participates to the regulation of different parameters such as the metabolic (lipolysis, lipogenesis and thermogeneis), and secretory (leptin and other adipokines) activities but also plasticity (proliferation differentiation and apoptosis) of adipose tissues. In turn the various fat pads will send information via sensory innervation of white adipose tissue as well as metabolic and hormonal signals acting directly on some brain areas. Altogether these results showed the presence of a neural feedback loop between adipose tissues and the brain which plays a major role in the regulation of energy homeostasis and as been shown to vary according to physiological and pathological states.     

Arrhythmias after surgery for complete transposition: Do they matter?

SummaryConcern about long-term complications after intraatrial repair of complete transposition has been used as an argument in favor of "anatomic" repair by the arterial switch operation. Late arrhythmias, including loss of sinus rhythm and the development of supraventricular tachycardias, particularly atrial flutter, are widely reported after intraatrial repair. Despite modifications of technique, the electrophysiologic substrate for arrhythmia results from the extensive atrial surgery required. Arrhythmias occur, even in the "modern surgical era" after both Mustard and Senning operations, are progressive, and appear to be inevitable. The circulation after an intraatrial repair is more vulnerable to the effects of excessive tachycardia, and this may place the patient at risk from sudden cardiac death. Current attempts at individual stratification of risk are disappointing using even aggressive electrophysiologic approaches, and a combined assessment involving hemodynamics is likely to be necessary. The electrophysiologic and arrhythmic consequences of the arterial switch operation have been less extensively researched but, as might be expected, are quite different from those seen after intraatrial repair. The atrial activation sequence is relatively undisturbed, and sinus nodal dysfunction and supraventricular arrhythmia are uncommon. Ventricular extrasystoles are the arrhythmia most consistently found during the short follow-up currently available. In the longer term, myocardial ischemia, hemodynamic disturbances and autonomic imbalance may predispose to late arrhythmia. Current evidence would suggest that the lack of clinically significant arrhythmia and the restoration of the left ventricle to the systemic circulation are significant advantages of the arterial switch operation over intraatrial repair procedures.