Hemodynamic comparison of different multisites and multipoint pacing strategies in cardiac resynchronization therapies

Purpose

Late cure after a previously failed ablation of ventricular arrhythmias (VAs) is a relatively common phenomenon. The present study sought to delineate the incidence and electrophysiological characteristics of late cure in idiopathic VA patients.

Methods

Totally, 45 idiopathic VA cases (mean age 44?±?18 years, 27 males) either failed acutely or recurred within 12 h were enrolled in this study. Based on intensive clinical observations in the acute period, 19 (42%) patients demonstrated late cure in the first week after the procedure.

Results

The late cure patients had significantly better acute and cumulative ablation effects during the procedure than did those without a late cure. Additionally, they had a prediction that originated from the right ventricular outflow tract, aortic-mitral continuum, and left summit area relative to other sites (13/18 vs 6/27, p?<?0.01). In a median follow-up of 24 [14, 46] months, 7/19 (37%) patients had their VAs recurred. The late cure group had significantly more patients cured at long-term follow-up than those without (12/19 vs 0/26, p?<?0.01). A cutoff value of the “time to eliminate VAs” >?7.0 s was able to predict a long-term recurrence of the VAs with 62.5% sensitivity and 85.7% specificity.

Conclusions

The late cure of VAs occurs in more than one third of patients who have a seemingly unsuccessful ablation session, which is clustered in the first week after the procedure. However, long-term recurrence of VAs occurred in 37% of the late cure patients, emphasizing the importance of long-term follow-up.

     

Hand‐foot‐skin reaction related to use of the multikinase inhibitor sorafenib and hard orthotics

Hand‐foot‐skin reaction is a distinct clinical condition arising in association with the use of multikinase inhibitors, including sorafenib. Because multikinase inhibitors are increasingly being used in children with cancer, recognition of this previously unfamiliar condition is of importance to pediatric dermatologists. We describe the diagnosis and successful treatment of a case of hand‐foot‐skin reaction in a child taking sorafenib for an unresectable desmoid tumor.     

In vivo effects of Bothrops jararaca venom on metabolic profile and on muscle protein metabolism in rats

This study investigated the in vivo effects of the Bothrops jararaca venom (BjV) on general metabolic profile and, specifically, on muscle protein metabolism in rats. The crude venom (0.4 mg/kg body weight, IV) was infused in awake rats, and plasma activity of enzymes and metabolites levels were determined after 1, 2, 3, and 4 hours. BjV increased urea, lactate, and activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase after 4 hours. The content of liver glycogen was reduced by BjV. Protein metabolism was evaluated by means of microdialysis technique and in isolated muscles. BjV induced increase in the muscle interstitial-arterial tyrosine concentration difference, indicating a high protein catabolism. The myotoxicity induced by this venom is associated with reduction of protein synthesis and increase in rates of overall proteolysis, which was accompanied by activation of lysosomal and ubiquitin-proteasome systems without changes in protein levels of cathepsins and ubiquitin-protein conjugates.     

Down-regulation of mannosyl receptor-mediated endocytosis and antigen F4/80 in bacillus calmette-guerin-activated mouse macrophages. Role of T lymphocytes and lymphokines

Bacillus Calmette-Guerin (BCG) infection alters the surface and endocytic properties of mouse peritoneal macrophages (PM) compared with thioglycollate- elicited (TPM) or resident PM (RPM). Expression of Ia antigen (Ag) is enhanced up to fourfold, but plasma membrane receptors that mediate binding and uptake of mannosyl/fucosyl-terminated glycoconjugates (MFR), Fc receptors, and the macrophage (m)-specific Ag F4/80 are reduced by 50-80 percent. Levels of Mac-1 remain relatively stable. These changes are accompanied by enhanced secretion of O(2)(-), after further stimulation with phorbyl myristate acetate, and of plasminogen activator. Both these products are released by TPM, but not RPM. The characteristic surface phenotype of BCG-PM can also be induced by injection of C. parvum, another m- activating agent, but not by thioglycollate broth, lipopolysaccharide, or proteose peptone. Purified protein derivative (PPD) and N-acetylmuramyl-L- alanyl-D-isoglutamine. 2H(2)0 are soluble agents with partial activity. Alteration of m markers by BCG infection depends on T lymphocyte function, although studies with nude mice indicate that other pathways may also serve to modify the surface of the m. M from uninfected animals displayed all markers of activation after adoptive transfer of specifically-sensitised lymphocytes with PPD, intraperitoneally, or after co- cultivation. Treatment of primed lymphocytes with anti-Thy-1 antibody and complement ablated this effect. Lymphokines obtaned by Ag or mitogen stimulation induced similar changes in TPM and RPM. Mannose-specific endocytosis decayed rapidly, time 1/2 approximately equal to 16 h and stabilized at approximately 25 percent of control values. Single-cell analysis showed that residual MFR activity was uniform in the target population. Loss of Ag F4/80 after activation by lymphocyte and PPD was less marked than after infection (35 percent vs 80 percent), unlike MFR activity, which declined to a similar extent. Induction of m Ia by lymphokine reached a peak after 2-3 d and was lost within 2 d of its removal. Recovery of MFR and F4/80 was incomplete under these conditions. These studies establish that activated m known to display enhanced antimicrobial/anticellular activity express markedly different surface properties distinct from elicited or resident cells. The role of antigen- stimulated T cell products in regulating m function is confirmed, and down-regulation of mannosyl-receptor-mediated endocytosis provides a sensitive, quantitative, and cell-specific new marker to study their properties and mechanism of action. Extensive, but selective remodeling of m plasma membrane structure could play an important role in controlling recognition and effector mechanisms of the activated m.     

Economic analysis of two structured treatment and teaching programs on asthma

The aims of the present study were as follows:

• 1). to evaluate the medical outcomes of two treatment and educational asthma programs
• 2). to determine by cost-analysis both cost and economic outcome of the programs
• 3). to perform a cost-benefit analysis (determining the net cost-benefit) and a cost-effectiveness analysis (determining the cost per unit of effect and the incremental cost-effectiveness ratio) from the perspective of health program policy makers (HPP; indirect costs, i.e., loss of productivity, excluded) and of society as a whole (Saw; all costs included).

Patients were randomly assigned to a complete (CP; n = 32) or reduced (RP; n = 33) program: the RP group received a reduced education (self-reading of an educational booklet on asthma), while the CP group attended an “asthma school”, consisting of six lessons based on the same booklet and including educational videotapes. Both programs included peak-flow monitoring and treatment according to international guidelines, and follow-up. The outcome variables (asthma attacks, urgent medical examinations, admission days, working days lost) did not differ significantly between CP and RP. Morbidity savings were $1894.70 (CP) and $1697.80 (RP) according to Saw, and $1349.50 and $1301.80, respectively, according to HPP. The net cost-benefit was $1181.50 for CP and $1028.00 for RP, and the cost-benefit ratio per dollar spent was 1:2.6 for CP and 1:2.5 for RP, according to Saw. One day of admission prevented had a cost of $110.20 (CP) and $94.10 (RP). CP gave slightly better results and was slightly more cost-effective than RP in improving patients' welfare. It cannot be excluded that the retrospective analysis used to determine baseline costs might have inflated differences for both groups. Sensitivity analysis was slightly in favor of RP when the outcome variables were tested at their upper and lower 95% CI.