Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities

Cytogenetic studies of 68 patients who developed secondary leukemia (SL)/dysmyelopoietic syndrome (DMS) after extensive chemotherapy and/or radiation therapy as well as patients who developed SL/DMS without such treatment showed that those patients who received radiation alone or with chemotherapy had more extensive numerical and structural abnormalities than those who received only chemotherapy. In terms of the specific chromosomal abnormalities, there are no differences between the various treatment groups. Hypodiploidy is the most common form of aneuploidy in these patients, with the most common numerical abnormality being the loss of chromosome 7. The most common structural abnormalities involved chromosomes 3 and 5. When compared with patients with de novo leukemia and DMS, the chromosomal abnormalities in these patients are more complex and extensive. Serial studies revealed that cytogenetic abnormalities do not precede the development of hematologic changes by significant time periods.     

Correction of the platelet adhesion defect in delta-storage pool deficiency at elevated hematocrit--possible role of adenosine diphosphate

Previous studies on patients with storage pool deficiency (SPD) who are specifically deficient in platelet dense granules (delta-SPD) have suggested a role for dense granule substances, in all likelihood adenosine diphosphate (ADP), in mediating thrombus formation on subendothelium at high shear rates. The role of dense granule substances in mediating platelet adhesion appears to be more complicated Previous studies in delta-SPD suggested an adhesion defect that was strongly influenced by the patient's hematocrit (Hct) value. To explore further the possibility that red blood cells (RBCs) may influence the role that platelet storage granules play in mediating adhesion at high shear rates, we have measured adhesion (and thrombus formation) throughout a preselected range of Hct values (30% to 60%) in normal subjects and in patients with delta-SPD. The present studies confirm the defect in platelet adhesion in patients with delta-SPD, most significantly at Hct values of 30% to 40%. This defect (but not that of thrombus formation) can be completely corrected by the addition of RBCs. The correction of the platelet adhesion defect by RBCs was specific for delta-SPD; it was not observed in either von Willebrand's disease or thrombasthenia. Studies performed on normal blood under conditions that could be expected to block any effect of ADP on adhesion and an analysis of the type of adhesion defect in delta-SPD suggest that ADP may be involved in the process required for platelet spreading on the subendothelium. The corrective effect of RBCs on platelet adhesion in delta-SPD appears to be chemical rather than physical in nature, possibly due to shear-induced release of RBC ADP or to other recently described properties of RBCs that enhance collagen- induced platelet interactions.     

Clinical predictors of chronic chagasic myocarditis progression

INTRODUCTION AND OBJECTIVES: Previous prognostic studies of Chagas' disease have focused on mortality associated with end-stage cardiopathy (i.e., heart failure). Our aim was to identify indicators of progression in early-stage Chagas' heart disease. MATERIAL AND METHOD: The study included 856 patients with 3 positive anti-Trypanosoma cruzi test results. Those with heart failure were excluded. Patients were divided into 3 clinical groups: those without heart disease (Group I); those with heart disease but without left ventricular enlargement (Group II); and those with left ventricular enlargement but without heart failure (Group III). The endpoint was progression to a more severe clinical stage or death due to cardiovascular disease. A Cox regression model was used to derive a clinical risk score from clinical, electrocardiographic and echocardiographic variables. RESULTS: At study entry, the patients' mean age was 43.7 years. They were followed up for a mean of 8 years. The following were predictors of heart disease progression: age at entry (HR=1.05; 95% CI, 1.02-1.07; P<.001), left ventricular systolic diameter (HR=1.06; 95% CI, 1.04-1.09; P<.001), intraventricular conduction abnormalities (HR=1.85; 95% CI, 1.02-3.36; P=.04), and sustained ventricular tachycardia (HR=3.97; 95% CI, 1.65-9.58; P=.002). Treatment with benznidazole reduced the risk of progression (HR=0.40; 95% CI, 0.23-0.72; P=.002). The devised clinical risk score was effective in stratifying the likelihood of cardiopathy progression. CONCLUSIONS: Specific clinical indicators and a derived clinical risk score can be used to predict the progression of chronic chagasic myocarditis in patients without heart failure.     

Electrical conditioning of in situ skeletal muscle for replacement of myocardium

Eight canine right hemidiaphragms were electrically stimulated at 2Hz (N = 3) and 10 Hz (N = 5) for up to 135 days. ATPase histochemical studies showed nearly total transformation of type II fast twitch fatigable muscle fibers to type I slow twitch fatigue resistant muscle fibers. The thickness and vascular perfusion of the stimulated muscle increased significantly. Electrical thresholds remained unchanged. The muscle contracted vigorously and without fatigue for up to 135 days at 10 Hz stimulation. Electrical conditioning of canine diaphragm skeletal muscle at 10 Hz frequency for 5 weeks results in a 95% and greater population of slow twitch fatigue resistant muscle fibers. This change in diaphragmatic skeletal muscle should make it a more suitable autograft for replacement or augmentation of diseased cardiac muscle.     

Inflammation and adipose tissue: effects of progressive load training in rats

Introduction

Cytokines (IL-6, IL-10 and TNF-α) are increased after exhaustive exercise in the rat retroperitoneal (RPAT) and mesenteric adipose tissue (MEAT) pads. On the other hand, these cytokines show decreased expression in these depots in response to a chronic exercise protocol. However, the effect of exercise with overload combined with a short recovery period on pro- and anti-inflammatory cytokine expression is unknown. In the present study, we investigated the regulation of cytokine production in the adipose tissue of rats after an overtraining-inducing exercise protocol.

Methods

Male Wistar rats were divided into four groups: Control (C), Trained (Tr), Overtrained (OT) and recovered overtrained (R). Cytokines (IL-6, TNF-α and IL-10) levels and Toll Like Receptor 4 (TLR4), Nuclear Factor kBp65 (NF-kBp65), Hormone Sensitive Lipase (HSL) and, Perilipin protein expression were assessed in the adipose tissue. Furthermore, we analysed plasma lipid profile, insulin, testosterone, corticosterone and endotoxin levels, and liver triacylglycerol, cytokine content, as well as apolipoprotein B (apoB) and TLR4 expression in the liver.

Results

OT and R groups exhibited reduced performance accompanied by lower testosterone and increased corticosterone and endotoxin levels when compared with the control and trained groups. IL-6 and IL-10 protein levels were increased in the adipose tissue of the group allowed to recover, in comparison with all the other studied groups. TLR-4 and NF-kBp65 were increased in this same group when compared with both control and trained groups. The protein expression of HSL was increased and that of Perilipin, decreased in the adipose in R in relation to the control. In addition, we found increased liver and serum TAG, along with reduced apoB protein expression and IL-6 and IL-10 levels in the of R in relation to the control and trained groups.

Conclusion

In conclusion, we have shown that increases in pro-inflammatory cytokines in the adipose tissue after an overtraining protocol may be mediated via TLR-4 and NF-kBp65 signalling, leading to an inflammatory state in this tissue.     

Pregnancy in lung transplant recipients

Eight female lung transplant recipients, all of whom became pregnant after transplant, were reported to the National Transplantation Pregnancy Registry from US transplant centers. Outcomes of the 8 pregnancies were 4 live births, 3 therapeutic abortions, and 1 spontaneous abortion. Three of the 4 newborns were premature, with low birth weight (< 2500 grams). Rejection during pregnancy occurred in 3 pregnancies (38%). All 8 transplant recipients reported at least 1 complication during pregnancy, including shortness of breath, rejection, and infection. Two of the 4 deliveries were by cesarean section. At follow-up, all children were developing well with no residual problems. Female lung transplant recipients may face higher risks during pregnancy than other solid organ transplant recipients.     

Effects of local anesthetics on human platelets: filopodial suppression and endogenous proteolysis

Agents that affect platelet shape may be useful in understanding the mechanism of shape change; for this reason the effects of local anesthetics are worthy of further study. Local anesthetics cause platelets to retract filopodia. At short time intervals (up to about 30 min) and low concentrations of the drugs, the filopodia are reextended when the platelets are gel filtered with eluant free of anesthetic. At longer time intervals (1-2 hr) or higher drug concentrations, the retraction becomes irreversible. When the polypeptide composition of the total platelet lysate was examined on SDS gels, proteolysis of two high molecular weight bands was seen when the suppression became irreversible. These polypeptides, estimated as 250,000 and 230,000 daltons, were major components of a precipitate that formed when platelets were lysed at low ionic strength and were also enriched in a "cytoskeletal" preparation made by lysing platelets attached to glass beads and analyzing the adherent residue. Electron micrographs of platelets lysed on surfaces showed an intermeshed network of filaments to be a major component of the residue. The results suggest that the proteins comprised of these bands may be part of the cytoskeletal system and that their integrity may be necessary for the platelet to reextend filopodia following suppression.     

Evidence for the presence of tissue factor activity on subendothelium

By a variety of methods, tissue factor activity was demonstrated in the subendothelium of rabbit aorta and human umbilical artery. In one method, everted segments of de-endothelialized vessels were mounted in an annular perfusion chamber and the subendothelial surface was exposed to nonanticoagulated human blood under controlled flow. Procoagulant activity was assessed by measuring fibrin deposition on subendothelium and fibrinopeptide A (FPA) levels in post chamber blood. Both fibrin deposition and FPA were decreased with rabbit vessel segments exposed (at a shear rate of 650 seconds-1) to blood from patients with factor VII deficiency and with umbilical artery segments (at shear rates of 90 to 180 seconds-1) that had been pretreated with a monoclonal antibody to human tissue factor. In a second method, everted umbilical artery segments were mounted on a stir bar and the subendothelial surface was exposed, with stirring, to plasma or purified coagulation factors. The capacity of the surface to clot plasma on addition of calcium was inhibited by the antibody to tissue factor. The surface also activated purified 3H-factor X in the presence of factor VIIa, but not in its absence, and this surface property was almost entirely eliminated by pretreating the vessel segments with antitissue factor. Tissue factor activity in subendothelium could play a role in both the arrest of bleeding and in promoting the formation of thrombi at sites of vascular injury.