IgE antibody against surface antigens of Leishmania promastigotes in American cutaneous leishmaniasis

As IgE-mediated immune mechanisms participate in the host defence against some types of parasites, we evaluated sera from American cutaneous leishmaniasis (ACL) patients for the presence of this antibody against Leishmania. Using monoclonal antibodies against human IgE and an immunoperoxidase staining technique, 48% of the patients sera tested were found to contain IgE antibody that bound strongly to Leishmania promastigotes. A much lower proportion of sera from non-symptomatic subjects from either endemic or non-endemic areas of the disease contained significant levels of anti-Leishmania IgE antibody (6.5% and 0% respectively). The results indicated that the IgE antibody bound predominantly to surface components of the promastigotes, and reactivity against the intracellular amastigote form of the parasite was rarely detected. Somewhat unexpectedly, in a small proportion of the sera, the IgE antibody showed apparent specificity for L. mexicana or L. braziliensis. This study demonstrates that ACL patients can develop anti-Leishmania IgE antibody responses, that seem to be directed preferentially against surface antigens of promastigotes, and that can be strain specific. This raises the question as to the possible contribution of this antibody to the immune defence mechanisms against the parasite.     

Electrophysiologic Effects of the New Class III Antiarrhythmic Drug Dofetilide Compared to the Class IA Antiarrhythmic Drug Quinidine in Experimental Canine Atrial Flutter:

Effects of Dofetilide in Canine Atrial Flutter. Introduction: Previous studios that Class III antiarrhythmic drugs are more effective in reentrant arrhythmias because they prolong refractoriness (ERP) and wavelength and reduce dispersion of refractoriness compared to Class IA antiarrhythmic drugs, which slow conduction velocity (CV) in addition to their effects on refractoriness. Methods and Results: To test this hypothesis, the Class III drug dofetilide and the Class IA drug quinidine were studied in the experimental canine crush-injury model of atrial flutter, utilizing right atrial multipoint programmed stimulation and activation mapping. In seven dogs dofetilide prolonged ERP by 23%, slowed CV by 9% at 200-msec cycle length (P < 0.001) and by 39% at 150-msec cycle length (P < 0.001), and increased wavelength by 11% (P < 0.02). Dofetilide reduced dispersion of ERP by 20% (P = 0.003) and adjacent electrodes with ERP difference ≥: 20 msec by 76% (P < 0.001). Dofetilide slowed atrial flutter by 37% (P = 0.003) prior to terminating and suppressing it in all dogs. In eight dogs quinidine prolonged ERP by 14% (P < 0.001), slowed CV by 14% at 200-msec cycle length (P < 0.00) and by 19% at 150-msec cycle length (P < 0.001), and reduced wavelength by 2% (P = NS). Quinidine did not reduce dispersion of refractoriness. Quinidine slowed atrial flutter by 57% (P < 0.001), terminating and suppressing it in only three dogs. Efficacy of dofetilide was greater than quinidine (P = 0.026) and correlated with reduced dispersion of ERP (r = -0.653, P = 0.01), reduced adjacent electrodes with ERP difference ≥ 20 msec (r = -0.637, P = 0.012), and prolonged wavelength (r = 0.61, P = 0.018). Dofetilide and quinidine terminated atrial flutter by similar mechanisms. Myocardial fiber orientation was nonuniform around the crush injury. Conclusions: Antiarrhythmic efficacy of dofetilide was greater than that of quinidine and correlated with drug-induced prolongation of wavelength and reduction in dispersion of refractoriness, effects produced only by dofetilide.     

Eating problems at age 6 years in a whole population sample of extremely preterm children

Aim The aim of this study was to investigate the prevalence of eating problems and their association with neurological and behavioural disabilities and growth among children born extremely preterm (EPC) at age 6 years. Method A standard questionnaire about eating was completed by parents of 223 children (125 males [56.1%], 98 females [43.9%]) aged 6 years who were born at 25 weeks’ gestation or earlier (mean 24.5wks, SD 0.7wks; mean birthweight 749.1g, SD 116.8g), and parents of 148 classmates born at term (66 males [44.6%], 82 females [55.4%]). All children underwent neurological, cognitive, and anthropometric assessment, and parents and teachers completed a behaviour scale. Results Eating problems were more common among the EPC than the comparison group (odds ratio [OR] 3.6, 95% confidence interval [CI] 2.1–6.3), including oral motor (OR 5.2, 95% CI 2.8–9.9), hypersensitivity (OR 3.0, 95% CI 1.6–5.6), and behavioural (OR 3.8, 95% CI 1.9–7.6) problems. Group differences were reduced after adjustment for cognitive impairment, neuromotor disability, and other behaviour problems. EPC with eating problems were shorter, lighter, and had lower mid‐arm circumference and lower body mass index (BMI) even after adjusting for disabilities, gestational age, birthweight, and feeding problems at 30 months. Interpretation Eating problems are still frequent in EPC at school age. They are only partly related to other disabilities but make an additional contribution to continued growth failure and may require early recognition and intervention.     

Consent issues and pediatric regional anesthesia

The need for consent to regional anesthetic procedures varies considerably between countries. It is likely that legislation and professional guidance will tighten consent procedures, and in several countries detailed written consent is required for regional blockade. This article discusses aspects of consent to regional anesthesia in children.     

Vitamin A status in children who are prone to respiratory tract infections

The effect of Vitamin A supplementation on susceptibility to acute respiratory infections was investigated in a randomized controlled trial. One hundred and forty-seven preschool-age children with a history of frequent respiratory illness were randomized into Vitamin A supplemented (450 g/day) and placebo groups. Respiratory symptoms were recorded on a daily basis over a period of 11 months. The children who received the supplement experienced 19% fewer episodes of respiratory symptomatology ( P <0.05) than their placebo counterparts, despite the fact that their plasma retinol levels did not change. Children with a prior history of lower respiratory illness or of allergy benefited most from supplementation. The plausibility of a role for Vitamin A in the aetiology of respiratory proneness is reviewed.     

EFFECTS OF ALPROSTADIL AND PRAZOSIN ON MOTILITY, VIABILITY AND MEMBRANE INTEGRITY OF HUMAN SPERM

Purpose

We evaluated the effects of alprostadil, prazosin hydrochloride, and alprostadil/prazosin hydrochloride, agents used in the clinical treatment of male erectile dysfunction, on the motility, viability and membrane integrity of human sperm.

Materials and Methods

Ten healthy volunteers provided semen samples that were incubated with 0.4 mg./ml. alprostadil, 0.1 and 0.2 mg./ml. prazosin hydrochloride and 0.4 mg./ml. alprostadil plus 0.1 mg./ml. prazosin hydrochloride for 2 hours. Control incubations included polyethylene glycol 1450, the formulation vehicle for the clinical use of alprostadil and prazosin, and Ham's F-10 buffer. Serial evaluations of percent sperm motility, percent viability, membrane function (by hypo-osmotic swelling test) and several computer generated measurements of sperm motion, including straight line velocity, curvilinear velocity, linearity and amplitude of lateral head displacement, were made.

Results

None of the agents had a significant impact on the percentage of motile or viable sperm or on sperm membrane function. Incubation with 0.2 mg./ml. prazosin reduced straight line velocity and curvilinear velocity significantly compared with the other agents. These changes were most likely a direct result of the viscosity of the 0.2 mg./ml. prazosin solution and not a cellular or metabolic effect on the sperm.

Conclusions

Alprostadil and prazosin hydrochloride at doses used in transurethral therapy for erectile dysfunction have no effect on the motility, viability and membrane integrity of human sperm.     

HEMODYNAMIC EFFECTS OF TRANSURETHRAL ALPROSTADIL MEASURED BY COLOR DUPLEX ULTRASONOGRAPHY IN MEN WITH ERECTILE DYSFUNCTION

Purpose

We evaluated the hemodynamic effects of transurethral alprostadil in 21 patients with erectile dysfunction using color duplex ultrasonography.

Materials and Methods

Penile arterial diameter, peak flow velocity and end diastolic velocity were compared following intraurethral administration of 500 micro g. alprostadil and intracavernosal injection of 10 micro g. alprostadil.

Results

A dose of 500 micro g. transurethral alprostadil resulted in significant increases in corporeal blood flow comparable to those achieved with intracavernosal injection of 10 micro g. alprostadil as measured by duplex ultrasonography in men with erectile dysfunction. Transurethral alprostadil resulted in statistically significant increases in arterial diameter and peak flow velocity comparable to those achieved with intracavernosal injection. End diastolic velocities were higher after transurethral alprostadil than intracavernosal injections. Color ultrasonography following transurethral alprostadil showed arterial and venous hyperemia of the corpus spongiosum and corpora cavernosa. Furthermore, color ultrasonography revealed communicating vessels between the corpus spongiosum and corpora cavernosa following administration of transurethral alprostadil.

Conclusions

The visualization of communicating vessels between the corpus spongiosum and corpora cavernosa after transurethral alprostadil suggests local mechanisms of drug transfer from one to the other. In addition to potential clinical benefits, transurethral alprostadil may be useful to visualize the vascular anatomy of the penis and to test for patient responsiveness to local vasoactive agents.     

Benzidine Dihydrochloride: Risk Assessment

Benzidine Dihydrochloride: Risk Assessment. LITTLEFIELD, N.A., NELSON, C. J., AND GAYLOR, D. W. (1984). Fundam. Appl. Toxicol.4, 69–80. Benzidine, recognized as a bladder carcinogenin man and as a liver carcinogen in experimental animals, isthe chemical basis of as many as 200 commercial dyes. Physiologicalprocesses can metabolize these dyes to release benzidine, therebycreating a potential exposure hazard. To assess this hazard,both sexes of F₁ hybrid (genetically homogeneous) and monohybrid(genetically heterogeneous) mice from a BALB/c male and C57BL/6female cross were exposed for their respective lifespans tobenzidine dihydrochloride in their drinking water at concentrationsof 0, 30, 40, 60, 80, 120, and 160 ppm for males, and 0, 20,30, 40, 60, 80, and 120 ppm for females. Animals were removedfrom the study when they were dead or moribund. This study wasterminated after 33 months of exposure. Using the endpoint ofhepatocellular adenomas and carcinomas, the Armitage Doll multistagemodel was used to describe the tumor rates in the experimentaldose range and to obtain the upper confidence level on tumorrates. Linear interpolation was used between zero dose and theupper confidence level of the lowest experimental dosage forpredicting potential low dose tumor rates. Dose-response effectson body weight, survival, and liver neoplasms were noted inboth stocks. For each of the endpoints, the females were moresusceptible than males and the F₁ (homogeneous) stock was moresusceptible than the monohybrid cross (heterogeneous). The calculatedvirtually "safe" dose predicted to produce less than one permillion F₁ female mice with a liver tumor is 0.045 ppb. Onepart per billion of benzidine dihydrochloride in the drinkingwater of these mice is estimated to produce liver tumors inless than 2.23 mice per 100,000 population.