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Biomedical subjects

S Dixit

Publications and source records attributed to S Dixit.

At least 19 recordsLinked to original sources

Anti-filarial activity of novel formulations of albendazole against experimental brugian filariasis.

The study was aimed at developing better orally active albendazole (ALB) formulations. Six formulations (ALB-1 to ALB-6) were prepared and tested against Brugia malayi in Mastomys coucha and jird (Meriones unguiculatus) at 200 mg/kg, orally, for 5 consecutive days. The anti-filarial efficacy was assessed against microfilariae (mf), adult worms and female reproductive potential. Three of the 6 ALB formulations showed greatly improved female worm sterilizing potential (ALB-1: 90%; ALB-3: 63%; ALB-4: 77% of untreated control) in B. malayi - M. coucha model. Sterilization efficacy of ALB-1 was also better than that shown by pure-ALB (P<0.001) or its marketed tablet formulation, Zentel (P<0.01), while that of ALB-4 was better than pure-ALB (P<0.05). The activity of ALB-3, pure-ALB and Zentel was, however, comparable. ALB-1 also showed late microfilaricidal activity with a maximum of 78% fall in microfilarial count. In contrast, neither the pure ALB nor Zentel showed any microfilaricidal activity. In the jird - B. malayi model, ALB-1 and ALB-4 showed marginal sterilizing efficacy whereas pure ALB or Zentel were ineffective. In conclusion the anti-filarial efficacy of ALB-1 was found to be superior to pure-ALB or Zentel.

Albendazole↗

Protection against L3 induced Brugia malayi infection in Mastomys coucha pre-immunized with BmAFII fraction of the filarial adult worm.

The present study was aimed at investigating protective efficacy of BmAFII (Sephadex G-200 eluted fraction of Brugia malayi adult worm extract) against establishment of infective larvae (L3)-induced B. malayi infection in Mastomys coucha and to delineate immunological responses induced in the host. Healthy male M. coucha were immunized with BmAFII and subsequently inoculated with B. malayi L3. Specific IgG and cell mediated immune responses (cellular proliferation) including release of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta) and nitric oxide (NO) from host's cells stimulated with BmAFII or lipopolysaccharide (LPS)/concanavalin A (Con A) in vitro were determined. Immunization with BmAFII reduced the adult worm recovery by 85.7% (P<0.001) and microfilaraemia by 77-95% of unimmunized controls (P<0.05-0.01). Immunization alone resulted in downregulation of responses of cellular proliferation, IFN-gamma, TNF-alpha and NO production (P<0.01) but increased TGF-beta release (P<0.001) whereas the converse was seen after L3 inoculation in these animals. In unimmunized+L3 inoculated animals all the above parameters were found downregulated (P<0.01-0.001). The cell proliferative response of BmAFII immunized+L3 challenged animals was larger for Con A (P<0.001) but not for BmAFII. Specific IgG levels were higher in immunized, immunized+L3 inoculated and unimmunized+L3 inoculated groups (P<0.001) compared to unimmunized animals, the highest level being shown by immunized+L3 inoculated group. In conclusion, immunization with BmAFII suppresses establishment of L3-induced infection in M. coucha by stimulating proinflammatory responses to L3.

Animals↗

Justifying the need to prescribe limits for toxic metal contaminants in food-grade silver foils.

The use of silver foils in various food preparations is a common practice in Middle Eastern and South East Asian countries. The FAO/WHO Joint Expert Committee on Food Additives (JECFA) has included silver in the list of food additives, but specifications were not prepared. Indian food legislation has included food-grade silver foil and laid down a purity requirement of 99.9%. This leaves an unspecified margin of 0.1% or 1000 microg g(-1) for contaminants. Therefore, a study to investigate the levels of metallic contaminants in food-grade silver foil was undertaken. Of 178 foils analysed, 161 (90%) contained silver, whilst 10% were fraudulently made up of aluminium. In the case of silver foils, 46% of the samples adhered to the desired purity requirement of 99.9%, while 54% had a lower silver content. Copper was present in 86.3% of the silver foils, while chromium, nickel and lead contamination was found in over 54% of samples. Cadmium levels were detected in 28% of the silver foils and manganese was present in 6.8% of samples. In silver foils showing metal contaminants, average levels were found for nickel (487 microg g(-1)), lead (301 microg g(-1)), copper (324 microg g(-1)), chromium (83 microg g(-1)), cadmium (97 microg g(-1)) and manganese (43 microg g(-1)), which being appreciable justify the need to prescribe limits for some metals in food-grade silver foil as well as for silver powder used in confectioneries and medicinal preparations. The work reported here should encourage manufacturers to use high-purity raw materials and take suitable precautions to reduce unwarranted exposure of consumers to toxic metal contaminants.

Aluminum↗

Inflammatory antigens of Brugia malayi and their effect on rodent host Mastomys coucha.

The study was aimed at identifying pro- and anti-inflammatory cytokine releasing potential of Brugia malayi adult worm fractions and their role in filarial infection and pathogenesis. THP-1 cells were incubated with soluble somatic Brugia malayi adult worm extract (BmAS) and its Sephadex G-200 fractions BmAFI, BmAFII and BmAFIII and the effect of the fractions on parasitological, immunological and lymph node parameters was assessed in Mastomys coucha. BmAFII stimulated the pro-inflammatory TNF-alpha, IL-1beta and IL-6 release; IL-10 release was insignificant. Sensitization of animals with BmAFII and subsequent intraperitoneal implantation of worms enhanced CMI response. BmAFII also increased lymph node weight and cellularity, stimulated lymph node mast cells and eliminated intraperitoneally instilled worms. BmAFI stimulated several folds more release of IL-10, whereas TNF-alpha release was negligible. Sensitization with BmAFI elicited low CMI responses, moderately stimulated mast cells and facilitated survival of implanted adult parasites. Fifty percent of naive animals exposed to BmAFI showed oedematous lymph nodes and increased node weight. NCP-bound molecules corresponding to BmAFI and II showed cytokine-stimulating potential in vitro. It is concluded that BmAFII is protective and stimulates pro-inflammatory cytokines, whereas BmAFI facilitates parasite survival and stimulates IL-10.

Animals↗

Responses of Mastomys coucha, that have been infected with Brugia malayi and treated with diethylcarbamazine or albendazole, to re-exposure to infection.

The responses of Mastomys coucha to re-exposure to infection with homologous infective larvae (L(3)) of Brugia malayi were investigated, after initial infections with the nematode had been treated subcutaneously for 5 days with diethylcarbamazine (DEC; 150 mg citrate/kg. day) or albendazole (ALB; 50 mg/kg. day). The parasite burdens, serum concentrations of IgG reacting with a soluble somatic extract of adult B. malayi (BmAS), and cytokine and lymphocyte-proliferative responses to filarial antigen (BmAS) or mitogen (concanavilin A or lipopolysaccharide) were studied. The results demonstrated, for the first time, that re-infection with L(3) was only successful in the DEC-treated animals, not the ALB-treated ones. When the ALB-treated animals were re-exposed, interferon-gamma production decreased, lymphocyte-proliferative responses either remained the same (with concanavilin A) or decreased (with BmAS), and concentrations of specific IgG decreased. When the DEC-treated animals were re-exposed, microfilaraemias re-appeared and, although production of interferon-gamma decreased, there were no detectable lymphocyte proliferative responses, and concentrations of specific IgG remained unchanged. Taken together, the results indicate that, at least in the M. coucha model of human filariasis, ALB but not DEC treatment may help to prevent the development of re-infections.

Albendazole↗

Molecular segregation observed in a concentrated alcohol-water solution.

When a simple alcohol such as methanol or ethanol is mixed with water, the entropy of the system increases far less than expected for an ideal solution of randomly mixed molecules. This well-known effect has been attributed to hydrophobic headgroups creating ice-like or clathrate-like structures in the surrounding water, although experimental support for this hypothesis is scarce. In fact, an increasing amount of experimental and theoretical work suggests that the hydrophobic headgroups of alcohol molecules in aqueous solution cluster together. However, a consistent description of the details of this self-association is lacking. Here we use neutron diffraction with isotope substitution to probe the molecular-scale structure of a concentrated alcohol water mixture (7:3 molar ratio). Our data indicate that most of the water molecules exist as small hydrogen-bonded strings and clusters in a 'fluid' of close-packed methyl groups, with water clusters bridging neighbouring methanol hydroxyl groups through hydrogen bonding. This behaviour suggests that the anomalous thermodynamics of water alcohol systems arises from incomplete mixing at the molecular level and from retention of remnants of the three-dimensional hydrogen-bonded network structure of bulk water.

Journal Article↗

Clinical characteristics and catheter ablation of left ventricular outflow tract tachycardia.

Left ventricular outflow tract (LVOT) tachycardia is an uncommon form of idiopathic ventricular tachycardia (IVT). The underlying mechanism of this arrhythmia appears to be cyclic AMP-medicated triggered activity. The tachycardia occurs in the absence of structural heart disease and is generally benign, presenting commonly as palpitations and presyncope. It can manifest either a right or left bundle branch block morphology with an inferior axis. Subtle variations in the QRS morphology in leads I, V1, and V2 can help in localizing the anatomic site of origin (SOO). The arrhythmia is typically responsive to a variety of pharmacologic agents (beta-blockers, calcium channel blockers, Class I and II agents). Radiofrequency catheter ablation of LVOT tachycardia SOO as determined by pace mapping is quite efficacious (success rates of 90%). Magnetic electroanatomic mapping augments this by permitting three-dimensional catheter mapping and reproducible localization of the SOO. Catheter ablation should be considered relatively early in patients who experience severe symptoms with their arrhythmia and have failed, or are reluctant to take medications for the disorder.

Catheter Ablation↗

Cardiac involvement in patients with acute neurologic disease: confirmation with cardiac troponin I.

BACKGROUND: Patients with acute neurologic illness often manifest findings suggestive of cardiac injury. Their proper interpretation is unclear. Accordingly, we conducted a blinded evaluation to assess the incidence of cardiac injury determined by elevations of cardiac troponin I (cTnI) in patients presenting within 24 hours of a neurologic event and to determine their short- and long-term prognostic effect. METHODS: Blood samples for measurement of cTnI levels were obtained on hospital admission and daily for 3 days and were run by immunoassay. Extensive clinical evaluations including electrocardiograms and echocardiograms were obtained from all patients; daily follow-up evaluations were performed. The clinical electrocardiographic, echocardiographic, and biochemical data were analyzed independently by blinded observers. RESULTS: Peak levels of cTnI were elevated (> or =0.4 microg/L) in 17 patients (19%) (mean + SD, 2.5 + 2.7 microg/L). All patients with elevated cTnI levels had clinical, electrocardiographic, or echocardiographic evidence of cardiac injury except those (n = 5) with minor elevations. One-year mortality was 29% (23/80). Early death (< or =30 days) accounted for 44% of total mortality (n = 10) and was significantly higher in patients with elevated cTnI levels (Wilcoxon P =.01; odds ratio, 6. 4). This difference was less marked by 1 year (Wilcoxon P =.07). CONCLUSIONS: There is a substantial prevalence of myocardial injury in patients with acute neurologic illness. Cardiac injury in this population, as in others, seems to adversely affect prognosis.

Acute Disease↗

Status epilepticus associated with cefepime.

Cefepime is a fourth-generation cephalosporin widely used for gram-negative sepsis. The authors report two patients in whom nonconvulsive status epilepticus developed while they were on treatment with cefepime for Pseudomonas aeruginosa infection. The status epilepticus resolved completely once the drug was withdrawn. Cefepime therapy can result in status epilepticus, especially if given in higher doses than required.

Adult↗

Esophageal biopsy for the diagnosis of gastroesophageal reflux-associated otolaryngologic problems in children.

Recently, gastroesophageal reflux (GER) has been found to contribute to many types of otolaryngologic pathology in infants and children. The complaints may be intermittent and unresponsive to usual therapies, such as antimicrobial treatments. A high index of suspicion for GER and for the concept of "silent" GER (GER without overt symptoms) is necessary for accurate diagnosis and treatment of otolaryngologic manifestations of GER in these patients. In this prospective historical cohort study, the records were reviewed from 101 children who underwent esophagoscopy and biopsy as a diagnostic test for GER at the time of other otolaryngologic procedures. Significant associations were found between the presence of histologic esophagitis and asthma, recurrent croup, cough, apnea, sinusitis, stridor, laryngomalacia, subglottic stenosis, posterior glottic erythema, and posterior glottic edema. There were no complications. Esophageal biopsy is a rapid, safe and effective diagnostic test for GER that should be considered at the time of other procedures in children with selected GER-associated problems.

Biopsy↗

The relation between stress fractures and bone mineral density: evidence from active-duty Army women.

OBJECTIVE: To determine if bone mineral density (BMD) is associated with the probability of stress fractures in premenopausal women. DESIGN: Case-control study. SETTING: Large Army post, Fort Lewis, WA. PARTICIPANTS: Twenty-seven active duty Army women with documented stress fractures within the last 2 years and 158 female controls. METHODS AND MAIN RESULTS: All subjects were examined and interviewed. BMD of the femoral neck and posteroanterior lumbar spine (L2-L4) was measured using dual energy X-ray absorptiometry. Univariate comparisons revealed no significant differences in BMD of the femoral neck or lumbar spine between groups. Women with stress fractures had a significantly higher exercise intensity (428 vs 292 minutes per week, p<.05) and were more likely to be entry-level enlisted soldiers (63% vs. 44%, p<.05) than those without stress fractures. Multivariate analyses revealed a strong negative association between femoral neck BMD and the probability of stress fractures (lower BMD, higher risk). Exercise intensity and body mass index had a significant positive effect on BMD of the femoral neck and lumbar spine, yet both were associated with an increased probability of stress fractures. CONCLUSIONS: Femoral neck BMD was significantly associated with the probability of stress fractures. Optimal training programs should balance the beneficial indirect effect of increased exercise (through increased BMD) with its detrimental direct effect on stress fractures.

Adult↗

Spatially distributed dominant excitation frequencies reveal hidden organization in atrial fibrillation in the Langendorff-perfused sheep heart.

INTRODUCTION: Atrial fibrillation (AF) is characterized by complex wave propagation, yet periodic excitation suggesting a high degree of organization may be revealed during sustained AF. We provide a systematic quantification of the spatial distribution of dominant frequencies (DFs) of local excitation on the epicardium of the right atrial (RA) free wall and left atrial (LA) appendage of the isolated sheep heart during AF. The data reveal, for the first time, hidden organization, independent of the activation sequences or nature of electrograms. METHODS AND RESULTS: In 13 Langendorff-perfused sheep hearts, AF was induced in presence of 0.1 to 0.6 microM acetylcholine. Video movies (potentiometric dye di-4-ANEPPS) of the RA and LA (>30,000 and >20,000 pixels, respectively) were obtained at 120 frames/sec and a biatrial electrogram was recorded. Spectral analyses were performed on movies with DF maps constructed. During AF, the activity formed stable discrete domains with uniform DFs within each domain. Acceleration of AF increased the number of domains (R = 0.81, P < 0.0001) and the DF variance (R = 0.63, P < 0.001), indicating a decrease in organization. Also, the LA was faster and more homogeneous, with smaller number of DF domains, compared to the RA (P < 0.00001). CONCLUSION: In this model, AF is characterized by multiple domains with distinct DFs on the atrial epicardium. The decrease in domain area with increased rate suggests that AF results from high-frequency impulses that undergo spectral transformations. The LA is generally faster and more organized than the RA, suggesting that the sources for the impulses are localized to the LA.

Animals↗

Reducing obesity via a school-based interdisciplinary intervention among youth: Planet Health.

OBJECTIVE: To evaluate the impact of a school-based health behavior intervention known as Planet Health on obesity among boys and girls in grades 6 to 8. DESIGN: Randomized, controlled field trial with 5 intervention and 5 control schools. Outcomes were assessed using preintervention (fall 1995) and follow-up measures (spring 1997), including prevalence, incidence, and remission of obesity. PARTICIPANTS: A group of 1295 ethnically diverse grade 6 and 7 students from public schools in 4 Massachusetts communities. INTERVENTION: Students participated in a school-based interdisciplinary intervention over 2 school years. Planet Health sessions were included within existing curricula using classroom teachers in 4 major subjects and physical education. Sessions focused on decreasing television viewing, decreasing consumption of high-fat foods, increasing fruit and vegetable intake, and increasing moderate and vigorous physical activity. MAIN OUTCOME MEASURES: Obesity was defined as a composite indicator based on both a body mass index and a triceps skinfold value greater than or equal to age- and sex-specific 85th percentiles. Because schools were randomized, rather than students, the generalized estimating equation method was used to adjust for individual-level covariates under cluster randomization. RESULTS: The prevalence of obesity among girls in intervention schools was reduced compared with controls, controlling for baseline obesity (odds ratio, 0.47; 95% confidence interval, 0.24-0.93; P = .03), with no differences found among boys. There was greater remission of obesity among intervention girls vs. control girls (odds ratio, 2.16; 95% confidence interval, 1.07-4.35; P = .04). The intervention reduced television hours among both girls and boys, and increased fruit and vegetable consumption and resulted in a smaller increment in total energy intake among girls. Reductions in television viewing predicted obesity change and mediated the intervention effect. Among girls, each hour of reduction in television viewing predicted reduced obesity prevalence (odds ratio, 0.85; 95% confidence interval, 0.75-0.97; P = .02). CONCLUSION: Planet Health decreased obesity among female students, indicating a promising school-based approach to reducing obesity among youth.

Adolescent↗

Association of maternal short stature with stunting in Mexican children: common genes vs common environment.

OBJECTIVE: To evaluate the association between stunting in children and maternal short stature, controlling for potential environmental confounders. DESIGN: 1988 Mexico National Nutrition Survey. SETTING: Mexico SUBJECTS: The final sample size was 4663 pairs of children (<5 y) and their mothers (12-49 y) from a total of 13 236 surveyed houses. MAIN OUTCOME MEASURES: Stunting (height-for-age Z-scores <-2). RESULTS: The prevalence of stunting in children was 19%, and 10% of the mothers exhibited short stature (<145 cm). In the crude analysis, mothers with short stature were significantly more likely to have stunted children (odds ratio (OR)=4.0; 95% confidence interval (CI)=3.2-4.8; P-value <0.001). In a multiple logistic regression model the OR for child stunting was reduced, but remained significant OR=2.0; 95% CI=1.6-2.6; P-value <0.001) after adjustment for region, urban/rural residence, socio-economic status, household size, child age and presence of infection in the past 14 d, and maternal age, body mass index (BMI), and educational level. Adjusted ORs varied between regions (Mexico City, OR=3.9; North Mexico, OR=3. 1; Central Mexico, OR=2.0; South Mexico, OR=1.6. Comparison of crude vs adjusted estimates pointed to regional differences in the proportion of association between maternal and child short statures explained by environmental determinants. CONCLUSIONS: Maternal stature, reflecting her potential height and early environment, appeared to contribute to child height independently of the shared risk factors that could affect stature. Nonetheless, we could explain much of the association between stunting in children and maternal short stature by environmental factors, and part of the residual variability may be due to unmeasured determinants. Regional differences pointed to a predominance of environmental factors in explaining child stunting in poorer regions.

Adult↗

Surgery versus surgery and postoperative radiotherapy in squamous cell carcinoma of the buccal mucosa: a comparative study.

BACKGROUND: The efficacy of postoperative radiotherapy for squamous cell carcinoma of the buccal mucosa was evaluated. METHODS: One hundred seventy-six patients treated between 1989 and 1993 were analyzed. One hundred fifteen patients were treated with surgery alone (Group 1), and 61 patients were treated with a combination of surgery and postoperative radiotherapy (Group 2). RESULTS: Actuarial 3-year locoregional control in Groups 1 and 2 was 11% and 48% for patients with stage III + IV cancer (P = .001) and 71% and 75% for patients with stage I + II cancer (P = .74), respectively. On multivariate analysis for locoregional failure, surgical margin, bone invasion, high grade, and node involvement were significant factors in Group 1, whereas in Group 2 only tumor thickness was a significant factor. For local failure, margin, bone invasion, and stage in Group 1 and tumor thickness in Group 2 appeared as significant factors. For nodal failure, clinical nodal (cl N0 vs. N+) stage and grade in Group 1 and pathologic nodal stage (pN0 + 1 vs. pN2) in Group 2 were observed as significant factors. On subset analysis, postoperative radiotherapy was observed to have a significant advantage for surgical margins of 2 mm or less in both early pT (T1 + T2) (P = .019) and late pT (T3 + T4) (P = .016) stages. The local failure rate was higher if the time between surgery and radiotherapy was greater than 30 days. CONCLUSIONS: Postoperative radiotherapy was effective in decreasing locoregional failure in patients with close surgical margins, tumor thicker than 10 mm, high-grade tumors, positive node, and bone invasion. The effect of interval between surgery and postoperative radiotherapy on local failure was margin-dependent.

Adult↗

Compatibility evaluation of metered-dose inhaler valve elastomers with tetrafluoroethane (P134a), a non-CFC propellant.

Compatibility of propellants, excipients, and solvents with the components of the valve greatly influences performance of metered-dose inhalers (MDIs). Ozone-friendly hydrofluoroalkane propellant 134a has potential for use as a chlorofluorocarbon (CFC) replacement. No suitable replacement for propellant 11 and 114 has yet been found and the problems arising from this may be overcome by use of ethanol as a solvent. In this study, compatibility of MDI valve elastomers Dowty Nitrile 0117, White Buna, and Type 674 (B) with P134a placebo formulations having different concentrations of ethanol was investigated. The results indicate that formulations containing no ethanol adversely affected the functioning of the valves. Higher concentrations of ethanol improved valve performance, but showed increased leakage. Physical characteristics of the valve elastomers evaluated by determining swelling caused after exposure to the P134a placebo formulations exhibited increased swelling with increasing concentrations of ethanol in the formulation.

Administration, Inhalation↗

Safety and effectiveness of homemade and reconstituted packet cereal-based oral rehydration solutions: a randomized clinical trial.

OBJECTIVES: Parents may be deterred from obtaining commercial oral rehydration solutions (ORS) for their young children with acute diarrheal disease because of its availability and/or cost, especially if they are poor. We conducted a randomized clinical trial to determine 1) whether low-income parents could safely mix and administer cereal-based ORS (CBORS) both from ingredients commonly found in the home and from a premixed packet; 2) whether these CBORS were as effective in maintaining hydration as commercial glucose-based ORS; and 3) whether CBORS were more effective in reducing severity and duration of illness. METHODS: Children 4 to 36 months of age discharged from emergency departments and health centers with acute diarrheal disease were randomized to receive either homemade CBORS, reconstituted packet CBORS, or Pedialyte. A study nurse saw the child at home each day until the illness resolved, and obtained capillary blood for serum sodium at enrollment and at 24 to 48 hours; a sample of CBORS for sodium concentration; stool for pathogen analysis; and daily fluid intake, stool frequency, and weight. RESULTS: A total of 232 children were enrolled, of whom 203 (88%) completed the study. Two parents (3%) in the homemade CBORS group and one parent (1%) in the packet CBORS group made mixing errors resulting in a high sodium concentration (>100 mEq/L); their children refused the solution and had normal serum sodium values. Mean CBORS sodium concentration for the remainder of the homemade CBORS group was 60 +/- 10 mEq/L, and for the packet CBORS group, 54 +/- 13. Eighteen children (11%) had abnormal serum sodium values at presentation, which returned to normal in all groups in most cases. Three children (4.5%) in the homemade CBORS group, 4 (6%) in the packet CBORS group, and 1 child (1.4%) in the Pedialyte group failed therapy. Children refused to take homemade CBORS and packet CBORS (43% and 32%, respectively) more often than Pedialyte (9%), and those in the CBORS groups tended to take less ORS and total fluids. There were no significant differences among the three groups in incidence of daily vomiting or stooling, duration of diarrhea, or weight gain. CONCLUSIONS: CBORS do not offer a clinically significant advantage over glucose-based ORS. Homemade CBORS represent a treatment option in carefully selected cases, but it is not the safest alternative for regular clinical use.

Acute Disease↗