Changes in locomotory behavior and cAMP produced in Ascaris suum by neuropeptides from Ascaris suum or Caenorhabditis elegans

Injection of Ascaris FMRFamide-like (AF) peptides and peptides encoded by genes in Caenorhabditis elegans were analyzed for effects on locomotion, body waveforms, and cAMP concentrations in adult female Ascaris suum. Injection of AF1 (KNEFIRFamide) or AF2 (KHEYLRFamide) inhibited the propagation of locomotory waves and reduced the number of waveforms, decreased the body length, and caused a large, long-lasting increase in cAMP. Muscle tissue was identified as a major source of the cAMP response induced by AF1. The AF1 analog AF1R6A did not affect cAMP levels by itself, but inhibited the cAMP response produced by AF1. AF8 (KSAYMRFamide) produced ventral coiling in the behavioral assay, and AF10 (GFGDEMSMPGVLRFamide) decreased the body length and increased the number of body waveforms. In dorsal muscle strips, AF10 produced a long-lasting contraction. Neither AF8 nor AF10 changed cAMP concentrations. AF17 (FDRDFMHFamide) increased body length and decreased cAMP. The neuropeptides encoded by C. elegans genes flp-4, flp-7, flp-9, and flp-13 produced paralysis and loss of waveforms, increased body length and, like AF17, decreased cAMP. Three new predicted peptides from C. elegans genome sequences were synthesized and tested. One produced ventral coiling but no change in cAMP; the other two gave no detectable responses. The fact that C. elegans neuropeptides produce behavioral and physiological effects in A. suum suggests that structurally related peptides may exist in A. suum. The profound changes in cAMP produced by some neuropeptides has important implications for understanding cAMP signaling and shows that neuropeptide-mediated signal transduction pathways are potential targets for anthelmintic drug development.     

A critical risk-benefit assessment argues against the use of anthracyclines in induction regimens for newly diagnosed childhood acute lymphoblastic leukemia.

Although anthracyclines are associated with significant cardiac toxicity and their benefit remains unclear, they are included in nearly all current protocols for the treatment of childhood acute lymphoblastic leukemia (ALL). Currently open trials from most major groups use anthracyclines in the induction phase for all high-risk patients and in the delayed intensification phase for all patients regardless of risk classification. Our review of published randomized studies reveals no benefit for the addition of anthracyclines to induction phase of childhood ALL regimens consisting of vincristine, prednisone, and L-asparaginase (VPL), with or without a delayed intensification phase. No randomized studies have evaluated the use of anthracyclines in the delayed intensification phase of therapy. Furthermore, studies of relapsed patients indicated no benefit for the addition anthracyclines to maintenance regimens. Recent evidence from preclinical studies suggests that a combination of VPL with an anti-CD19 immunotoxin is more effective than VPL plus anthracyclines combination. Accumulated evidence exists that anthracyclines are associated with late-onset cardiac morbidity in about 25% of childhood ALL and other cancer survivors, and about 5% develop overt heart failure, with some requiring cardiac transplantation. Anthracycline-induced cardiotoxicity in children has no safe dose threshold and all doses are likely to cause significant myocardial damage. New data suggests that a unique cardiac mitochondrial exogenous NADH dehydrogenase is responsible for the anthracycline-induced oxygen radicals damage to the heart, and that chelators currently evaluated may not prevent late-onset cardiotoxicity in children. In view of these findings we urge extreme caution in using anthracyclines as part of multimodality ALL treatment programs, and strongly recommend reevaluation of what should be considered the best induction regimen for high-risk childhood ALL.     

Vascular access for hemodialysis by bovine graft arteriovenous fistulas.

A technique has been developed for vascular access in chronic dialysis using bovine graft arteriovenous fistulas in the forearm. Indications for use of bovine arteriovenous fistulas are failures of arteriovenous shunts and standard arteriovenous fistulas at the wrist or as a primary procedure in the event that arterial inflow or venous outflow are inadequate. Choice of either a straight or loop graft is dictated by the vascular anatomy. Loop grafts, orginating from the brachial artery, should be used for inflow problems; straight grafts, originating from an artery at the wrist, should be used for outflow problems. Results have been excellent in this series of 39 grafts in 36 patients observed from two months to one year with a follow-up average of six months. Ninety per cent of the grafts continue to function or functioned until successful transplantation or the death of the patient. Advantages of bovine graft arteriovenous fistulas compared with other fistulas include ease of access, high flows and decreased incidence of hematomas. The major complication has been thrombosis, and this incidence, most likely, can be decreased by more careful selection of the type of graft placement according to the vascular anatomy.     

Determination of left ventricular mass with ultrafast CT and two-dimensional echocardiography

Conventional methods for determining mass of the left ventricle (LV) require geometric assumptions. Eleven patients were studied with ultrafast computed tomography (CT) and with two-dimensional echocardiography (2-D echo) for calculation of LV mass. With ultrafast CT, calculations were performed on end-systole images and end-diastole images for each patient. Comparisons of the results from ultrafast CT with those from 2-D echo were made with linear, Spearman rank, and interclass correlation coefficients, as well as with slope and intercept values of regression lines. Adequate ultrafast CT and 2-D echo studies were obtained in nine of the 11 patients. After the systolic and diastolic ultrafast CT determinations of LV mass were averaged, the results demonstrated excellent agreement with the 2-D echo determinations (slope = 1.0 +/- 0.20, r = .89, P less than .002).     

Diabetes and the Heart – Revisited

Ohne Zusammenfassung