Use of polyethylene glycol solution in slow transit constipation

Patients with long-standing functional slow-transit constipation were treated with low daily doses of polyethylene glycol solutions. Bowel frequency, stool consistency and colonic transit time improved markedly during the treatment. No relevant side-effects were reported during the study period.     

Phosphoinositide 3-kinase gamma-deficient hearts are protected from the PAF-dependent depression of cardiac contractility

OBJECTIVES: Following an ischemic insult, cardiac contractile recovery might be perturbed by the release of autacoids, like platelet-activating factor (PAF), that depress heart function by acting through G protein-coupled receptors (GPCRs). The signaling events downstream the PAF receptor that lead to the negative inotropic effect are still obscure. We thus investigated whether the GPCR-activated phosphoisositide 3-kinase gamma (PI3Kgamma) could play a role in the cardiac response to PAF. METHODS: The negative inotropic effect of PAF was studied ex vivo, in isolated electrically driven atria and in Langendorff-perfused whole hearts derived from wild-type and PI3Kgamma-null mice. Postischemic recovery of contractility was analyzed in normal and mutant whole hearts subjected to 30 min of ischemia and 40 min of reperfusion in the presence or absence of a PAF receptor antagonist. RESULTS: While wild-type hearts stimulated with PAF showed increased nitric oxide (NO) production and a consequent decreased cardiac contractility, PI3Kgamma-null hearts displayed reduced phosphorylation of nitric oxide synthase 3 (NOS3), blunted nitric oxide production and a complete protection from the PAF-induced negative inotropism. In addition, Langendorff-perfused PI3Kgamma-null hearts showed a better contractile recovery after ischemia/reperfusion, a condition where PAF is known to be an important player in depressing contractility. In agreement with a role of PI3Kgamma in this PAF-mediated signaling, postischemic contractile recovery in PI3Kgamma-null mice appeared overlapping with that of normal hearts treated with the PAF receptor antagonist WEB 2170. CONCLUSION: These data indicate a novel PAF-dependent signaling pathway that, involving PI3Kgamma and NOS3, contributes to postischemic contractile depression.     

Classification and histological, immunohistochemical, and molecular diagnosis of inflammatory myocardial disease

In the WHO 1996 classification of cardiomyopathies, myocarditis is defined as an “inflammatory disease of the myocardium associated with cardiac dysfunction” and is listed among “specific cardiomyopathies”. Myocarditis is diagnosed on endomyocardial biopsy (EMB) by established histological, immunological, and immunohistochemical criteria, and molecular techniques are recommended to identify viral etiology. Infectious, autoimmune, and idiopathic forms of inflammatory cardiomyopathy are recognized that may lead to dilated cardiomyopathy. According to Dallas criteria, myocarditis is diagnosed in the setting of an “inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes, not typical of ischemic damage associated with coronary artery disease”. The majority of experts in the field agree that an actual increase in sensitivity of EMB has now been reached by using immunohistochemistry together with histology. A value of >14 leukocytes/mm² with the presence of T lymphocytes >7 cells/mm² has been considered a realistic cut off to reach a diagnosis of myocarditis. The development of molecular biological techniques, particularly amplification methods like polymerase chain reaction (PCR) or nested-PCR, allows the detection of low copy viral genomes even from an extremely small amount of tissue such as in EMB specimens. Positive PCR results obtained on EMB should always be accompanied by a parallel investigation on blood samples collected at the time of the EMB. According to the recent Association for European Cardiovascular Pathology guidelines, optimal specimen procurement and triage indicates at least three, preferably four, EMB fragments, each 1–2 mm in size, that should immediately be fixed in 10 % buffered formalin at room temperature for light microscopic examination. In expected focal myocardial lesions, additional sampling is recommended. Moreover, one or two specimens should be snap-frozen in liquid nitrogen and stored at ?80 °C or alternatively stored in RNA-later for possible molecular tests or specific stains. A sample of peripheral blood (5–10 ml) in EDTA or citrate from patients with suspected myocarditis allows molecular testing for the same viral genomes sought in the myocardial tissue.     

Aldosterone and potassium balance in dialysis patients.

Sir, The article by Hussain et al. [1], showing that spironolactone,even at dosages as low as 25 mg/day, may cause dangerous hyperkalaemiain some dialysis patients (two out of 15 patients) reminds usof the importance of aldosterone-driven potassium (K) secretionin extrarenal sites (among others, the colon, salivary and sweatglands) in uraemia [2,3]. Though extrarenal K excretion is <10%of total K excretion in subjects