Two multidrug fixed-dosage treatment regimens with multibacillary leprosy patients

This study compares the clinical, bacilloscopic, and histopathological evolution of 140 patients classified as having multibacillary leprosy with no previous specific treatment who were submitted to two multidrug treatment regimens with a fixed dose. Regimen I-Group 1: 70 cases received 600 mg rifampicin (RMP) + 100 mg dapsone (DDS) daily for three consecutive months followed by 100 mg DDS daily, self-administered doses for 21 months. Regimen II-Group II: 70 cases received 600 mg RMP + 300 mg clofazimine (CLO) once a month under supervision plus self-administered doses of 50 mg CLO + 100 mg DDS daily for 24 months. The bacilloscopic, histopathological and neuromotor evaluation parameters showed no statistically meaningful differences (P > 0.05) between the two groups except for reaction frequency (P < 0.05) in that group II patients presented the least number of reactional episodes during the treatment and in the dermatological examination at discharge. Follow-up after treatment was carried out for a consecutive four year period. During routine clinical examination one case submitted to regimen I developed nodular skin lesion over the right arm. Skin biopsy was done for histopathological examination and mouse foot-pad experiment by Shepard technique. The drug susceptibility test with DDS and RPM showed that M. leprae strain isolated was susceptible to both the drugs.     

Effect of homocysteine on copper ion-catalyzed, azo compound-initiated, and mononuclear cell-mediated oxidative modification of low density lipoprotein

Homocysteine is an independent risk factor for cardiovascular diseases. The mechanisms by which elevated plasma concentrations of homocysteine are related to the pathogenesis of atherosclerosis are not fully understood. To examine whether homocysteine is implicated in atherogenesis through the modification of low density lipoprotein (LDL), the effect of homocysteine on the oxidation of LDL was studied by three different oxidation systems. Thus, LDL was subjected to Cu(2+)-catalyzed, azo compound-initiated, and peripheral blood mononuclear cell-mediated oxidative modification. The extent of modification was assessed by measuring the formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances, and the relative electrophoretic mobility. Homocysteine at a normal plasma concentration (6 microM) showed no effect, whereas a concentration corresponding to moderate hyperhomocysteinemia (25 microM) or to concentrations seen in homocystinuria patients (100, 250, and 500 microM) protected LDL from modification of the lipid as well as of the protein moiety. One exception was observed: when the oxidation was initiated by copper ions, homocysteine at concentrations 6 and 25 microM stimulated the lipid peroxidation of LDL to a small, but statistically significant extent. High concentrations of homocysteine showed antioxidative properties as long as the thiol groups were intact, thereby delaying the onset of the oxidation. The 1,1-diphenyl-2-picrylhydracyl radical test demonstrated that homocysteine at concentrations > or = 50 microM possessed marked free radical scavenging capacity. Finally, LDL isolated from two patients with homozygous homocystinuria showed similar extent of Cu(2+)-catalyzed oxidation as LDL from a group of healthy control subjects. Taken together, our data suggest that low concentrations of homocysteine in the presence of copper ions may enhance the lipid peroxidation of LDL, whereas high concentrations of homocysteine may protect LDL against oxidative modification in the lipid as well as in the protein moiety. Thus, homocysteine-induced atherosclerosis may be explained by mechanisms other than oxidative modification of low density lipoprotein.     

The multiyear changes in the epidemic activity of the foci of zoonotic cutaneous leishmaniasis at the Murgab oasis. I. An analysis of the relations of morbidity to heliogeophysical factors

Attempts were made to analyse the relationships of changes in the pattern of zoonotic cutaneous leishmaniasis (ZCL) morbidity by the 1951-1993 statistics of the Turkmenistan Ministry of Health by the areas of Mary?ski? velaiat with heliogeophysical factors. For quantitative characterization of solar activity changes, various indices were used; among them there was the Wolf number, radio radiation flux at a wavelength of 10.7 cm. and the geomagnetic Aa-index. In some many-year observations, vague cyclic variations were detected on a personal computer by spectral and periodogram analyses proved to be effective in other diseases. Correlation and cross-correlation analyses were used to evaluate the possible relationships between the morbidity rates and the changes in heliogeophysical factors. The study has revealed that the epidemic activity of ZCL foci is characterized by cyclicity with variations of about 2.4, 3.6, 6.9, and 11.2 years. The changes in ZCL morbidity in the areas, including the natural ZCL foci of Murgab delta landscapes, slightly differ from those in the areas with valley foci in the south part of the velayat in the duration and expression of cycles. At the same time sun-caused 11-year cycles are observed in all groups of the areas, though they are slightly more pronounced in the north than in the south. The greatest epidemic outbreaks (1956-1957, 1965, 1977, and 1986-1988) occurred in various areas of the Murgab oasis on an average of 1-3 years after the minimum of 11-year solar cycles. Noteworthy, they are greatly marked in odd solar activity cycles (the 1957 and 1977 outbreaks) in many areas. Among the parameters chosen, the radio flux of solar radiation at a wavelenght of 10.7 cm and the Wolf number (the correlation coefficients are as high as 0.30-0.50 at P = 0.95) are closely related with ZCL morbidity changes when the plot is shifted. At the same time the values of the geomagnetic Aa-index are unlikely to greatly affect changes in the epidemiological situation. The regularities revealed are of particular significance for long-term prediction of the greatest rises of ZCL morbidity rates. Taking into account the estimated solar activity changes within the next years, one may expect activation of natural ZCL foci and, in case of untimely use of prophylactic measures, the following rise in the population's morbidity in 1998-1999.     

The role of nitric oxide in mechanisms of the nephrotoxic effect of verografin

A clinic based cross-sectional study was conducted at Immunoprophylaxis Clinic at Govt. Medical College, Nagpur. Mothers of 217 children were interviewed for infant feeding practices. In 62.67% of children, breast-feeding was initiated within 24 hrs. after birth. About 22% mother used prelacteal feed and 70% mothers preferred demand feeding. Prominent area of concern includes discarding of colostrum, low exclusive breast feeding rate, delayed weaning and early termination of breast feeding. Further improvement in present day infant feeding practices is possible by emphasising on the health education component of existing nutritional programmes.     

Preliminary immunohistochemical characterization of a monoclonal antibody (PRO:4-216) prepared from human prostate cancer nuclear matrix proteins

OBJECTIVES: A nuclear matrix protein (PC-1) was previously identified and reported to be present only in human prostate cancer but absent in tissue from the same prostate containing either benign prostatic hyperplasia (BPH) or normal prostate tissue. The PC-1 protein was identified by high resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and exhibited a molecular mass of 56 kDa and an isoelectric point of 6.58. This work investigates the immunohistochemical characterization of PRO:4-216, a monoclonal antibody to PC-1. METHODS: Areas of the 2D-PAGE gels containing the human prostate cancer nuclear matrix proteins near PC-1 were isolated, eluted, and injected into mice to develop monoclonal antibodies. Antibodies were screened by immunofluorescence for nuclear reactivity to a human prostate cancer cell line (LnCaP) and by 1D and 2D Western blots for reactivity with prostate cancer nuclear matrix proteins. Monoclonal antibodies from the selected clones were affinity purified. The monoclonal antibody PRO:4-216 was used to analyze frozen tissue from 20 cancerous, 22 BPH, and 22 normal regions from fresh human prostate specimens. Tissue sections were analyzed for their immunohistochemical (IHC) (horseradish peroxidase) staining. RESULTS: Using a reference value for positive staining at an IHC score of greater than 50, 85% (17 of 20) of the cancerous, 5% (1 of 22) of the BPH, and 9% (2 of 22) of the normal prostate tissues stained positive. The one BPH and two normal tissues that stained positive were taken from prostates in which the adjacent cancerous tissue also demonstrated high IHC scores (greater than 225). CONCLUSIONS: These data demonstrate nuclear reactivity on fresh frozen human prostate cancer tissue for the monoclonal antibody PRO:4-216. PRO:4-216 may aid in distinguishing normal prostate and BPH from cancerous tissue.     

Comparison of patient-assisted epidural analgesia with continuous-infusion epidural analgesia for postoperative patients

Number of electroconvulsive therapy (ECT) treatments administered and severity of psychopathology confound the interpretation of clinical studies that address the relationship between the rate of administration of ECT and cognitive morbidity occasioned by the treatment. A preclinical study was therefore conducted to address the issue. Three groups (n = 8/group) of adult male Sprague-Dawley rats received six electroconvulsive shocks (ECS) in daily ECS, 3 ECS/week, and 2 ECS/week schedules; a fourth group (control; n = 8) received only sham ECS. From days 2 to 7 after the conclusion of the ECS/sham ECS course, the rats were monitored for learning on the Hebb-Williams complex maze. The control, 2 ECS/week, and 3 ECS/week groups showed significant learning by days 3, 5, and 7, respectively, while the daily ECS group showed no significant learning during the assessment period. This indicates that even when the cumulative effect of ECS on learning is controlled for, more frequent ECS is associated with slower learning. Extrapolating to clinical settings, it is suggested that wider spacing of ECT may lessen ECT-induced cognitive morbidity.     

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom hospital

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89% being less than 60 years of age compared to 40% at NCH (p < 0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI and renovascular disease and chronic pyelonephritis at NCH. Nephrotic syndrome occurred more frequently at UHWI than at NCH but the numbers were small (p < 0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p < 0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76% v 19% on haemodialysis). At UHWI, CAPD was not available and 45% of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.     

The dynamics of cardiac contraction in dogs with alloxan diabetes

Development of alloxan diabetes was accompanied in dogs by regular changes in the phasic structure of the cardiac contractions. Direction of the changes in the indices of phasic analysis in the groups of dogs with an average (up to 144.3 +/- 12.5 mg%) and marked (up to 258.0 +/- 22.8 mg%) increase in the blood sugar level was the same, but their expression increased with the elevation of hyperglycemia. In marked hyperglycemia there was established an increase (in comparison with normal values) of the index of myocardial tension, a shortening of the period of ejection, a decrease of the mechanical coefficient and of the intrasystolic index, this coinciding with the character of changes of the corresponding indices in the patients suffering from diabetes mellitus, depending on the severity of the disease. The data obtained pointed to the significant influence of metabolic changes (assessed by hyperglycemia level) on the contractile function of the heart.     

The origin of ventricular arrhythmias 24 hours following experimental anterior septal coronary artery occlusion

The anterior septal coronary artery was acutely ligated in 16 open-chest anesthetized dogs to produce an infarct of the septal myocardium. Twenty-four hours following occlusion complete epicardial mapping and extensive plunge electrode recording techniques were used to localize the sites of origin and patterns of activation of the ventricular tachyarrhythmias that developed during recovery. The earliest electrical activity for 13 individual rhythms was recorded from surviving septal subendocardial Purkinje fibers at the margins of the infarct, in the right or left ventricle, directly underlying the sites of earliest epicardial breakthrough. The sites of origin were verified by demonstrating unchanged activation sequences during pacing through the electrode sites which recorded the earliest activity. None of the arrhythmias arose from the His bundle or bundle branches despite the fact that these tissues course directly through the necrotic septum. The data presented supports the hypothesis that ventricular arrhythmias occuring in the 24-36 hour post acute infarction period may originate in the surviving subendocardial Purkinje system. Our experimental model shows that in cases in which a malignant rhythm arises from a focus, whether it is due to enhanced automaticity or local re-entry, epicardial mapping alone may not identify the source of the arrhythmias. Extensive endocardial mapping may provide a more rational basis for surgical interventions designed to abolish these arrhythmias.