Cutaneous Leishmaniasis In India

Fifteen patients with cutaneous leishmaniasis were randomly selected for clinical trials with itraconazole. A single daily itraconazole dose of approximately 4 mg per 1 kg of body weight was administered to each patient with breakfast for 6 weeks. Five patients served as controls. On completion of therapy, ten cases in the study group (66.6%) were considered to be cured. No major adverse effects were reported. No significant changes were seen in the controls at the end of the study. The possibility of spontaneous recovery will be discussed in this report even though it is considered to be unlikely. Itraconazole has promising potential in cutaneous leishmaniasis therapy.     

Isolation and characterization of a metallothionein-like protein from monkey brain

A cadmium-binding protein from monkey brain has been isolated, purified and characterized. The absorption spectrum of this protein indicates the presence of Cu-Zn thionein in the normal monkey brain which has a strong affinity to bind cadmium. On cadmium exposure the protein sequestered most of the cadmium which entered the brain. The apparent molecular weight of this protein as determined on a gel filtration column calibrated with marker proteins has been found to be in the range of 11,500-12,000 Da. The ratio of absorbance at 254 nm/280 nm is more than 1 indicating the presence of cadmium-mercaptide bonds, which was further confirmed by the presence of 15 cysteine residues. Polyacrylamide gel electrophoresis of the protein shows 3 bands indicating the presence of 3 isometallothionein forms. Unlike hepatic or renal thioneins, the cadmium-binding protein in brain is not inducible following administration of cadmium. However, when antibodies raised against hepatic metallothionein were cross-reacted with brain Cd-binding protein, a line of identity was observed, indicating the 2 proteins are immunologically identical and share a high degree of structural similarity.     

Complete inhibition of allergic airway inflammation and remodelling in quadruple IL-4/5/9/13−/− mice

BACKGROUND: T-helper type 2 (Th2)-derived cytokines such as IL-4, IL-5, IL-9 and IL-13 play an important role in the synthesis of IgE and in the promotion of allergic eosinophilic inflammation and airway wall remodelling. OBJECTIVE: We determined the importance of IL-13 alone, and of the four Th2 cytokines together, by studying mice in which either IL-13 alone or the Th2 cytokine cluster was genetically disrupted. METHODS: The knock-out mice and their BALB/c wild-type (wt) counterparts were sensitized and repeatedly exposed to ovalbumin (OVA) aerosol. RESULTS: Bronchial responsiveness measured as the concentration of acetylcholine aerosol needed to increase baseline lung resistance by 100% (PC100) was decreased in IL-13-/-, but increased in IL-4/5/9/13-/- mice. Chronic allergen exposure resulted in airway hyperresponsiveness (AHR) in wt mice but not in both genetically modified mice. After allergen exposure, eosinophil counts in bronchoalveolar lavage fluid and in airways mucosa, and goblet cell numbers were not increased in IL-4/5/9/13-/- mice, and were only attenuated in IL-13-/- mice. Airway smooth muscle (ASM) hyperplasia after allergen exposure was prevented in both IL-13-/- and IL-4/5/9/13-/- mice to an equal extent. Similarly, the rise in total or OVA-specific serum IgE levels was totally inhibited. CONCLUSION: IL-13 is mainly responsible for AHR, ASM hyperplasia and increases in IgE, while IL-4, -5 and -9 may contribute to goblet cell hyperplasia and eosinophilic inflammation induced by chronic allergen exposure in a murine model. Both redundancy or complementariness of Th2 cytokines can occur in vivo, according to specific aspects of the allergic response.     

Effects of norepinephrine on the dog common carotid, coronary and renal arteries: in vitro studies

The effects of norepinephrine were studied on segments of the common carotid, left circumflex and renal arteries of dogs with the endothelium intact and removed. Norepinephrine induced a dose-dependent increase in tension in segments of the renal and carotid artery but did not produce any effect on the coronary artery. Although the absence of endothelium did not affect the magnitude of the norepinephrine-induced vasoconstriction of the renal artery, it elicited a more pronounced response in the carotid artery in which the endothelium was removed. Our data suggest that the vascular response to norepinephrine is dependent upon the specific arterial bed and, secondly, that the endothelium plays a determinant role in the magnitude of the response of the carotid artery.     

Atrial septal defect in older adults: atypical radiographic appearances

Atrial septal defect (ASD) is the most common congenital cardiac anomaly manifested in adulthood. Clinical and radiographic features are well defined in patients less than 30 years of age. In older patients, however, the clinical symptoms are often atypical, and the auscultatory findings may be misleading. The radiographic manifestations in older patients have not been well described. In the current study, of 70 patients over the age of 50 years with proved ASD, 21 (30%) had atypical radiographic features, including apparently normal vascularity, left atrial enlargement, pulmonary venous hypertension, and pulmonary edema. In a control group of 70 younger patients with ASD, only 5.7% had atypical findings. The development of pulmonary venous hypertension and pulmonary edema in older patients was associated with smaller defects and a higher prevalence of mitral valve disease, left ventricular dysfunction, and pulmonary arterial hypertension than seen in older patients with typical radiographic findings.     

Comparison of Three Methods for Obtaining Principal Components from Family Data in Genetic Analysis of Complex Disease

Three multivariate techniques used to derive principal components (PCs) from family data were compared for their ability to model family data and power to detect linkage. Using the simulated data from Genetic Analysis Workshop 12, the five quantitative traits were first adjusted for age, sex, and environmental factors 1 and 2. Then, standard PCs, PCs obtained from between‐family covariance, and PCs obtained from within‐family genetic covariance were derived and subjected to multivariate sib pair linkage analysis. The standard PCs obtained from the overall correlation matrix allowed identification of key features of the true genetic model more readily than did the other methods. For detection of linkage, standard PCs and PCs obtained from the between‐family genetic covariance performed similarly in terms of both power and type 1 error, and both methods performed better than the PCs obtained from within‐family genetic covariance. © 2001 Wiley‐Liss, Inc.     

Comparative studies on the effect of vitamin A, B1 and B6 deficiency on oxalate metabolism in male rats

The study was conducted to investigate the effect of vitamin A, B1 and B6 deficiency on oxalate metabolism in rats. A significant hyperoxaluria was the common observation in all the three vitamin deficiencies (vitamin B6 greater than vitamin A greater than vitamin B1). The activities of hepatic glycolate oxidase and glycolate dehydrogenase were markedly enhanced in vitamin-A- and vitamin-B6-deficient rats. However, lactate dehydrogenase levels remained unaltered in these deficiencies as compared to their respective pair-fed controls. Vitamin B1 deficiency of 4 weeks' duration could augment the activity of glycolate oxidase only, with no alterations in the glycolate dehydrogenase and lactate dehydrogenase levels. Intestinal oxalate uptake studies revealed increased bio-availability of oxalate from the gut in vitamin-A- and vitamin-B6-deficient rats. Thus, the results suggest the relative contribution of both exogenous as well as endogenous oxalate in the process of calculogenesis under various nutritional stress conditions in rat.     

Deep brain stimulation for control of intractable pain in humans, present and future: a ten-year follow-up

Deep brain stimulation with chronically implanted electrodes has provided satisfactory control of pain in patients with intractable chronic pain syndromes, which have been refractory to medication and other conventional modalities of management. In this series the authors present their experience with 48 patients who have been followed for periods ranging from 6 months to 10 years. Long-term pain control was achieved in 30 patients (63%). Both the periventricular gray and specific sensory thalamic nuclei have been used as targets. Our results indicate that there is an initial 2-year fall-off of pain control caused by idiopathic tolerance, with stable results thereafter, regardless of site of the implant. This is suggestive of some biochemical modification of tissues around the electrode. Patients with failed-back syndrome secondary to multiple disc operations fared well; those with pain secondary to progressive neurological disorders or cancer had only short-term pain relief, and those with thalamic pain, cauda equina injury, or phantom limb pain usually had a poor result. Deep brain stimulation, in selected patients, appears to provide long-term pain control safely with few side effects or complications.     

Effect of cyclosporine on rubella virus-specific immune responses in chronic progressive multiple sclerosis

Cyclosporine A (CsA) has been used in putative autoimmune diseases after sensitization to unknown antigens. We have previously shown that CsA prevented continued activation of T-cells in chronic progressive multiple sclerosis (CPMS) patients. The current study was undertaken to determine whether CsA, or CsA and prednisone (CsA + P) could suppress immune responses to a common recall antigen. Serum antibody levels were higher in all CPMS patients than age-matched normal controls. However, rubella antibody titers in the CsA or CsA + P groups were no different from a placebo-treated CPMS patient group. The lymphocyte responses to inactivated rubella virus of CsA and CsA + P-treated CPMS patients were lower than placebo and control but not statistically different. Therapy with both CSA and CSA + P was associated with significantly lower panel mixed leukocyte responses and Ta1 expression than in the placebo-treated group; CD3, CD4, CD8 antigen expression and active rosette formation by T-cells were similar for the three CPMS groups. These results suggest that while CsA exerts measurable effects on non-specific indicators of cellular immunity in CPMS patients, it may not be as effective in suppressing pre-existent specific immune responses.     

Fetal Oxygen Saturation Monitoring in Labour: An Analysis of 118 Cases

Summary: Fetal oxygen saturation (FSpO₂) was recorded during labour to determine the relationship between FSpO₂ and indicators of fetal well-being, including umbilical blood gases, xanthine (X), hypoxanthine (Hx) and Apgar scores. This is one of me largest reported series of fetal pulse oximetry, with 118 fetuses monitored for over 329 hours. Mean FSpO, for all cases was 46.9% (SD=9.1%). There was no correlation between FSpO, during the last 10 minutes of monitoring and arterial pH, Hx or X. A mean FSpO₂, ≤ 30% was associated with a 5 minute Apgar score of ≤ 7 in the majority of cases. One fetus had a mean FSpO₂, <30% during the final 10 minutes of monitoring and an umbilical arterial pH<7.20, while there were 10 fetuses with an umbilical arterial pH<7.20, and mean FSpO₂, ≥ 30%. As these numbers are small, a larger series is necessary to further characterize the small number of fetuses who are significantly hypoxic.