Gap phenomenon in “the right and left bundle branch systems” during retrograde conduction in man

Gap phenomenon in right and left bundle branch systems during retrograde conduction is described in two patients with manifest reentry within the His-Purkinje System (V₃ phenomenon). In this form of gap the premature impulse (S₂) initially blocked in the right bundle branch system and conducted retrogradely via the left bundle branch system as manifested by sudden prolongation of S₂H₂ interval and appearance of V₃. At close coupling intervals S₂ impulse encountered retrograde block in the left bundle branch system and resumed retrograde conduction via the right bundle branch system with S₂H₂ intervals shorter than critical value and was not followed by V₃. However, on further shortening the S₁S₂ intervals S₂ impulse blocked again in right bundle branch system and resumed conduction via the left bundle branch system with S₂H₂ intervals longer than critical values and V₃ reappeared. The mechanism of these gaps is not clear but we believe is similar to the one proposed in Types I and II gaps in antegrade bundle branch conduction and involves proximal delay allowing distal recovery. The similarities and differences between the gap phenomenon in bundle branches during antegrade and retrograde conduction are discussed.     

Solubilization of homopolymers and copolymers by block copolymer micelles in dilute solutions

Solubilization by micelles of a three-block copolymer poly(styrene-butadiene-styrene) with a polybutadiene core was studied by the light scattering method on three types of solubilizate: polybutadiene with (a) low and (b) high molar mass (with respect to the polybutadiene block of the copolymer), and (c) a block copolymer poly(styrene-butadiene-styrene) with a high content of butadiene. True solubilization of polybutadiene into the cores of spherical micelles occurs in case (a); in case (b) polybutadiene forms partially stabilized, emulsion-like large droplets. In case (c) stable mixed micelles are formed having either lower or higher molar mass with respect to that of the original micelles, depending on the ratio of molar masses and on the composition of both copolymers. A similarity between solubilization of hydrocarbons by micelles of soaps or surfactants in aqueous solutions and solubilization of polymers by copolymer micelles in selective solvents is pointed out.     

Chemoprevention of prostate cancer

Prostate cancer is a common malignancy with multiple potential opportunities for cancer prevention. As the genetic basis of this malignancy is further understood, prevention strategies will be developed for individual patients based on specific risk factors and pathways of carcinogenesis. The PCPT has conclusively proven that prostate cancer prevention is possible. The results of the SELECT should be available within several years. An enormous challenge for the medical community will be the development of an efficient strategy to evaluate the substantial number of dietary, behavioral, and pharmacologic prevention opportunities. Ultimately, the goal of prostate can-cer prevention is to (1) identify men who are destined to develop clinically significant prostate cancer, and (2) provide individualized agents to prevent disease development.     

The pharmacokinetics of artemether and lumefantrine in pregnant women with uncomplicated falciparum malaria

Objective To determine the pharmacokinetic properties of artemether and lumefantrine (AL) in pregnant women with recrudescent uncomplicated multi-drug resistant falciparum malaria.Methods Pregnant women who had recurrence of parasitaemia following 7 days supervised quinine treatment were treated with AL. Serial blood samples were taken over a 7-day period, and pharmacokinetic parameters were estimated. For lumefantrine, these data were compared in a population pharmacokinetic model with data from non-pregnant, mainly male adults with acute malaria.Results The pregnant women (five in the second trimester and eight in the third trimester) had lower concentrations of artemether, dihydroartemisinin and lumefantrine, and the elimination of lumefantrine in pregnant women was more rapid than reported previously in non-pregnant adults.Conclusion Pregnancy is associated with reduced plasma concentrations of both artemether and lumefantrine. This is likely to be of therapeutic significance as plasma concentrations of lumefantrine, after elimination of artemether, are an important determinant of cure. Further studies are needed to determine the optimum dose regimen of artemether-lumefantrine in pregnancy.     

Oral rehydration for viral gastroenteritis in adults: a randomized, controlled trial of 3 solutions

BACKGROUND: Pedialyte and Gatorade are advocated for the treatment of dehydration in viral gastroenteritis, but there is limited evidence to support their use. We examine the efficacy, safety, and palatability of Pedialyte, Gatorade, and a New Oral Rehydration Solution (N-ORS). This was a randomized double-blind trial conducted in an inpatient, community hospital. Seventy-five consecutive adult patients (male, 42; female, 33) admitted with viral gastroenteritis were randomized to receive Gatorade, Pedialyte, or N-ORS for 48 hours. A yogurt/rice diet was allowed ad libitum. Stool and urine output, electrolytes, fluid intake, body weight, hematocrit, and palatability of solutions were measured. RESULTS: Sixty completed the study. Stool frequency, consistency, and body weight improved (p < .001) in all 3 groups, but there was no difference between groups. Likewise, urine output, hematocrit, and correlations between fluid ingested, stool weight, or urine output were similar. At admission and 24 and 48 hours later, hypokalemia was observed in 7, 10, and 8 patients with Gatorade; 3, 2, and 1 with N-ORS; and 2, 2, and 1 with Pedialyte, respectively. Similarly, hyponatremia was observed in 6, 9, and 3 patients with Gatorade; 5, 3, and 4 with N-ORS; and 4, 5, and 4 with Pedialyte. Tastewise, Gatorade and N-ORS were rated higher (p < .05) than Pedialyte. Limitations were a smaller sample size and higher dropout (20%). CONCLUSIONS: Gatorade and N-ORS seem to be as effective as Pedialyte in correcting dehydration and in improving bowel symptoms. All 3 solutions were safe. Unlike other groups, hypokalemia persisted in the Gatorade group. Gatorade and N-ORS may be effective in the treatment of dehydration associated with mild viral gastroenteritis.     

Towards the development of a pediatric ventricular assist device

The very limited options available to treat ventricular failure in children with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device at the University of Pittsburgh (UoP) and University of Pittsburgh Medical Center (UPMC). Our effort involves a consortium consisting of UoP, Children's Hospital of Pittsburgh (CHP), Carnegie Mellon University, World Heart Corporation, and LaunchPoint Technologies, Inc. The overall aim of our program is to develop a highly reliable, biocompatible ventricular assist device (VAD) for chronic support (6 months) of the unique and high-risk population of children between 3 and 15 kg (patients from birth to 2 years of age). The innovative pediatric ventricular assist device we are developing is based on a miniature mixed flow turbodynamic pump featuring magnetic levitation, to assure minimal blood trauma and risk of thrombosis. This review article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.     

HIV prevention programmes for female sex workers in Andhra Pradesh,India: outputs,cost and efficiency

Background  

Female sex workers and their clients play a prominent role in the HIV epidemic in India. Systematic data on the outputs, cost and efficiency for HIV prevention programmes for female sex workers in India are not readily available to understand programme functioning and guide efficient use of resources.     

A high throughput approach for simultaneous estimation of multiple synthetic trioxane derivatives using sample pooling for pharmacokinetic studies

The present study describes the application of concept of sample pooling to increase the throughput of pharmacokinetic screening at drug discovery and development stage. An HPLC-UV method for the simultaneous estimation of three synthetic antimalarial compounds 99/357, 99/408 and 99/411 has been developed and validated in rat serum with internal standard for pharmacokinetic profiling. Drug compounds in serum were extracted by two-step liquid-liquid extraction with 2% isopropyl alcohol in n-hexane and quantitated using a validated gradient HPLC-UV method, which was made feasible for all compounds using gradient elution scheme. The method was validated in terms of HPLC reproducibility, linearity, specificity, recovery, accuracy and precision, freeze thaw stability and long-term storage stability. Excellent linear relationships (r>0.99) were obtained for calibration as well as analytical standards over a concentration range of 25-1000 ng/ml for three analytes. Recoveries were fond to be >85% for 99/408 and 99/357 and >70% for 99/411. The method developed for three analytes was found to be accurate and precise as bias and percent relative standard deviation (% R.S.D.) values were within limits (<20%). By employing sample pooling approach, plasma level - time profile following single intravenous dose of all three compounds were obtained in a fraction of the time required by conventional single compound dosing and analysis.