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Biomedical subjects

A Mishra

Publications and source records attributed to A Mishra.

At least 109 records · Page 6Linked to original sources

Acinetobacter sepsis in newborns.

OBJECTIVE: To evaluate the clinico-epidemiological profile of Acinetobacter sepsis in neonates. DESIGN: Retrospective study. SETTING: Level II Neonatal Care Unit. SUBJECTS: 79 neonates with blood culture positive for Acinetobacter. METHODS: Relevant information was collected on a predesigned proforma from the case records and analyzed for clinical and epidemiological characteristics. RESULTS: The incidence of Acinetobacter septicemia was 11.1/1000 live births. Fifty-five babies were hospital born, 24 were outborn. Out of these, 64.6% babies were born at term and 40.5% had a birth weight of 2500 g or more. A cluster of 53 cases was seen between May and September 1995. In cases with early onset sepsis (onset < 7 days of postnatal age), difficulty in breathing (n = 54), chest retraction (n = 35) and refusal to feed (n = 46) were seen more commonly as compared to late onset sepsis (p < 0.05). Complications observed included meningitis, bleeding manifestations and necrotising enterocolitis in three, six and five babies, respectively. The organism was sensitive to ciprofloxacin (96.2%), amikacin (92.4%) and gentamicin (87.3%). A response rate of 52.4% was observed with Ciprofloxacin in babies not responding to cefotaxime and amikacin combination. The overall mortality was 13.9%. CONCLUSION: Nosocomial Acinetobacter sepsis may affect fullterm, appropriate for gestational age babies. Clinical presentation is indistinguishable from Gram negative septicemia. Life threatening complications can also occur. Ciprofloxacin may prove to be useful drug in resistant cases.

Acinetobacter Infections↗

The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction.

OBJECTIVES: To develop a brief, reliable, self-administered measure of erectile function that is cross-culturally valid and psychometrically sound, with the sensitivity and specificity for detecting treatment-related changes in patients with erectile dysfunction. METHODS: Relevant domains of sexual function across various cultures were identified via a literature search of existing questionnaires and interviews of male patients with erectile dysfunction and of their partners. An initial questionnaire was administered to patients with erectile dysfunction, with results reviewed by an international panel of experts. Following linguistic validation in 10 languages, the final 15-item questionnaire, the international index of Erectile Function (IIEF), was examined for sensitivity, specificity, reliability (internal consistency and test-retest repeatability), and construct (concurrent, convergent, and discriminant) validity. RESULTS: A principal components analysis identified five factors (that is, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) with eigenvalues greater than 1.0. A high degree of internal consistency was observed for each of the five domains and for the total scale (Cronbach's alpha values of 0.73 and higher and 0.91 and higher, respectively) in the populations studied. Test-retest repeatability correlation coefficients for the five domain scores were highly significant. The IIEF demonstrated adequate construct validity, and all five domains showed a high degree of sensitivity and specificity to the effects of treatment. Significant (P values = 0.0001) changes between baseline and post-treatment scores were observed across all five domains in the treatment responder cohort, but not in the treatment nonresponder cohort. CONCLUSIONS: The IIEF addresses the relevant domains of male sexual function (that is, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), is psychometrically sound, and has been linguistically validated in 10 languages. This questionnaire is readily self-administered in research or clinical settings. The IIEF demonstrates the sensitivity and specificity for detecting treatment-related changes in patients with erectile dysfunction.

Adult↗

Significantly reduced incidence of stroke during coronary artery bypass grafting using transesophageal echocardiography.

OBJECTIVE: Protruding atheromas of thoracic aorta have been identified as a source of systemic emboli and a major cause of stroke following cardiac surgery. This prospective study used transesophageal echocardiography (TEE) to identify atherosclerosis of thoracic aorta intraoperatively. The influence of risk factors was studied. Finally the impact of modifying surgical technique on the outcome was evaluated. METHODS: Seven-hundred and ninety-two patients undergoing coronary artery bypass grafting (CABG) were evaluated with TEE. Depending on the location and extent of thoracic aortic disease various surgical modifications were carried out, e.g. hypothermic circulatory arrest with aortic arch atherectomy, CABG on beating heart and others. The stroke rate in this group of patients was determined and analysed. RESULTS: Of the 114 patients with grade II and III atheromas of aortic arch and ascending aorta in whom surgical modifications were done, none had stroke. The overall stroke rate in the study group was 0.76%, six patients had stroke. Stepwise logistic regression identified age, diabetes, serum triglycerides and VLDL as important risk factors. Associated carotid artery disease and calcium on chest X-ray (CXR) were identified as important predictors of disease. CONCLUSIONS: Intraoperative TEE is an invaluable modality for evaluating the thoracic aorta. There is significant reduction in stroke rate following identification of atheromas and modification of surgical technique.

Adult↗

Transmyocardial laser revascularisation combined with coronary artery bypass grafting without cardiopulmonary bypass.

OBJECTIVE: To achieve complete myocardial revascularisation in patients with diffuse coronary artery disease, patients with inordinately high risk of cardiopulmonary bypass (CPB) like severe systemic disease or diffuse atherosclerosis of the aorta. METHODS: We have adopted the technique of combining coronary artery bypass grafting (CABG) with transmyocardial laser revascularisation (TMLR) using 1000 W CO2 laser machine. TMLR is done to areas supplied by ungraftable arteries, while CABG without cardiopulmonary bypass is done to the left anterior descending artery (LAD) and/or right coronary artery (RCA). TMLR + CABG on beating heart without CPB has been performed on 56 patients. Age ranged from 37 to 81 years with a mean of 56.17. Four patients were in renal failure, two were redo CABG. Preoperatively 39.28% patients had angina class III and 10.71% had angina class IV. Four patients were on preoperative IABP support. RESULTS: The mean number of grafts was 1.09. Internal thoracic artery (ITA) was used in 96.4% of the patients. Five patients showed elevation of CPK-MB, while three patients had an increase in Troponin T. Mortality was 1.8% (one patient died of intractable ventricular arrhythmia). The mean follow-up is 9.2 months. Myocardial perfusion scanning showed a stepwise improvement in reversible ischemia increasing from 52% at baseline to 91% at 12 months; 90.9% of the patients were angina free at 12 months. Metabolic stress test demonstrated an average increase in exercise tolerance from 5.2 min at baseline to 9.4 min at 12 months. Metabolic equivalents (METs) increased from 4.5 at baseline to 9.4 at 12 months. The average 44% Karnofsky score preoperative also increased to 86% at 12 months. CONCLUSIONS: Our results indicate that the technique is surgically feasible and safe, with excellent short term results.

Adult↗

The congested-like tracheae gene of Drosophila melanogaster encodes a member of the mitochondrial carrier family required for gas-filling of the tracheal system and expansion of the wings after eclosion.

A recessive semi-lethal mutation resulting from the insertion of a P-lacW transposon at the cytological position 23A on the polytene chromosomes of Drosophila melanogaster was found to affect the unfolding and expansion of the wings resulting in a loss of venation and a marked decrease in their size. Lethality was polyphasic with numerous animals dying during early larval development and displaying apparently collapsed tracheal trees. The gene was therefore designated as congested-like tracheae, or colt. The colt mutation resulted from the insertion of a P-lacW transposon within the coding region of a 1.4-kb transcript. Wild-type function was restored by inducing a precise excision of the P-lacW transposon, while a deletion of the colt locus, produced by imprecise excision of the P element, showed a phenotype similar to that of the original P insert. The colt gene consists of a single exon and encodes a protein of 306 amino acids made of three tandem repeats, each characterized by two predicted transmembrane segments and a loop domain. The COLT protein shares extensive homology with proteins in the mitochondrial carrier family and particularly with the DIF-1 protein of Caenorhabditis elegans, which has been shown to be maternally required for embryonic tissue differentiation. Our analysis revealed that zygotic colt function is dispensable for normal embryonic morphogenesis but is required for gas-filling of the tracheal system at hatching time of the embryo and for normal epithelial morphogenesis of the wings.

Amino Acid Sequence↗

Inhaled asbestos fibers induce p53 expression in the rat lung.

Humans and rodents exposed to an aerosol of asbestos fibers develop lung injury that can lead to a fibroproliferative response culminating in excessive scarring and impaired lung function. To define the early events that precede asbestos-induced fibrotic lung disease, rats were exposed to an aerosol of chrysotile asbestos fibers for 5 h. At various times after exposure, the lungs of the asbestos-exposed animals were evaluated immunohistochemically for expression of the p53 tumor suppressor protein, a growth regulatory protein. p53 became detectable by immunostaining at the predicted sites of fiber deposition (the bronchiolar-alveolar duct bifurcations) by 24 h after exposure. The number of cells positive for p53 immunostaining increased to a maximal level at 8 days after exposure, decreased by 14 days and returned to a low basal level at the 30-day time point. Control groups of rats that were unexposed or exposed to an aerosol of iron beads were negative for p53 immunostaining throughout the 30-day assessment period. Simultaneous detection of the proliferating cell nuclear antigen (PCNA) at the sites of fiber deposition in the asbestos-exposed animals agrees with our previous finding that p53 binds and regulates the PCNA promoter.

Administration, Inhalation↗

Pharmacokinetics and biodistribution of samarium-153-labelled OC125 antibody coupled to CITCDTPA in a xenograft model of ovarian cancer.

The use of samarium-153 in the context of radioimmunotherapy of cancers has been limited by the instability of antibody labelling, which produces high uptake concentrations in liver and bone. This study compares the pharmacokinetics and biodistribution of 153Sm-labelled OC125 monoclonal antibody, in whole or F(ab')2 fragment form and with diethylene triamine penta-acetic acid (DTPA) or 6-p-isothiocyanatobenzyl diethylene triamine penta-acetic acid (CITCDTPA) coupling, in nude mice grafted subcutaneously with an ovarian adenocarcinoma line (SHIN-3) expressing CA125 antigen. The specific activity of the immunoconjugates was 18.5-55.5 MBq/mg, and their immunoreactivity exceeded 65%. With 153Sm-DTPA-OC125F(ab')2, the stability study in serum indicated that 50% of the metal remained bound to the antibody. The pharmacokinetic study showed a retention half-life of 25.1 h and blood clearance of 0.72 ml/h. The biodistribution study indicated tumour uptake of 4.53%+/-0.49% of injected activity per gram (%ID/g) at 24 h and tumour-to-liver and tumour-to-bone ratios of 0.23+/-0.02 and 1.54+/-0.49 respectively at 24 h. With 153Sm-CITCDTPA-OC125F(ab')2, serum stability was greater (87% of the metal remaining bound to the antibody), retention half-life was 22.25 h and blood clearance was 2.23 ml/h. Tumour was better targeted (8.30%+/-3.56%ID/g at 24 h), and tumour-to-liver and tumour-to-bone ratios were 1.17+/-0.36 and 7.08+/-3.09 respectively at 24 h. However, renal retention remained elevated (29.76%+/-9. 41%ID/g at 24 h). With intact IgG, renal uptake decreased (1.41%+/-0. 49%ID/g at 24 h), but tumour uptake was lower than with fragments (1. 46%+/-0.58%ID/g at 24 h). Liver uptake was higher (tumour-to-liver ratio 0.10+/-0.05), and blood clearance was slower. The stability and distribution of 153Sm-CITCDTPA were more favourable than those of 153Sm-DTPA for application in radioimmunotherapy. Quantitative analysis performed using digitized images obtained by conventional autoradiography and the imaging plate system indicated that the latter system is suitable for biodistribution studies of immunoconjugates.

Animals↗

Inclusion of supine period in short-duration pH monitoring is essential in diagnosis of gastroesophageal reflux disease.

Prolonged esophageal pH monitoring is the most accurate method for detecting abnormal gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). However, some investigators have found that short-duration postprandial pH monitoring in the upright position is also useful, while others have failed to find such results. Therefore, we have compared a 6-hr period of pH monitoring (3-hr postprandial period after daytime meal and 3-hr supine period) with a total 24-hr period in detecting abnormal gastroesophageal reflux. Sixty-five patients (44 men, mean age 41.3 years) with GERD and 16 healthy volunteers (11 men, mean age 34.3 years) underwent 24-hr pH monitoring according to a standard protocol. Various reflux parameters during 24-hr pH monitoring were compared with reflux parameters during the 6-hr period. Abnormal GER was detected in 56 patients presenting with typical symptoms of GERD (sensitivity 86.2%). These patients could be further divided into upright (N = 18), supine (N = 15), and combined (N = 23) refluxers, depending on the posture in which abnormal reflux occurred. Esophageal pH monitoring during the 3-hr postprandial upright period showed abnormal reflux in only 35 patients (sensitivity 53.8%; P < 0.00005, compared with the 24-hr pH monitoring period). Abnormal GER was identified in 13 of 18 upright, 19 of 23 combined, and only one of 15 supine refluxers, as well as in two of nine patients with normal 24-hr pH-metry. However, inclusion of the 3-hr supine monitoring period in the 3-hr postprandial upright period improved detection of abnormal GER to 78.5% (51 patients; P = NS compared with 24-hr pH monitoring period). This was related mainly to improved detection of abnormal GER in supine refluxers (11 of 15; 73.3%). Esophageal acid exposure time correlated significantly with severity of esophagitis only during the total and supine periods of both the 24- and 6-hr periods and not during the upright period. Esophageal acid clearance correlated significantly with increasing grades of esophagitis for the supine and total periods only. We conclude that 3-hr postprandial pH monitoring, as has been conventionally practiced, is not appropriate in the detection of abnormal GER; inclusion of a supine period in the short-duration pH monitoring schedule increases the detection of pathological reflux. We therefore recommend that a supine period should be included in short-duration pH monitoring schedules. We also found that supine reflex was the most important factor in the development of esophagitis.

Adult↗

Neoplastic transformation and aberrant cell-cell interactions in genetic mosaics of lethal(2)giant larvae (lgl), a tumor suppressor gene of Drosophila.

Homozygosity for lethal(2)giant larvae (lgl), a mutation in a tumor suppressor gene of Drosophila, induces neoplasia of the imaginal discs. To explore the developmental capacities of lgl mutant cells, we have investigated their growth and differentiation in genetic mosaics. Adult wings mosaic for lgl displayed abnormal growth and differentiation of the lgl mutant and neighboring wild-type cells, suggesting aberrant cell-cell interactions during development. lgl mutant clones also straddled the anteroposterior boundary of the wing imaginal disc, apparently due to failure of the cells of the anterior and the posterior compartment to segregate at the boundary. To further test if anteroposterior compartmentalization takes place in the neoplastic imaginal discs of lgl mutant larvae, we studied the expression of an engrailed (en)-specific lacZ reporter gene during progressive stages of their tumorous growth. Our results show that en is activated in the posterior compartments of the neoplastic imaginal discs. However, during later stages of tumorous overgrowth, the en-expressing and nonexpressing cells appear to show extensive intermixing. These observations suggest that neoplastic transformation of imaginal discs involves loss of their normal cell-cell interactions and signaling.

Animals↗

Epithelial hyperplasia of imaginal discs induced by mutations in Drosophila tumor suppressor genes: growth and pattern formation in genetic mosaics.

Lethal mutations in the giant discs (lgd) and fat (ft) tumor suppressor genes of Drosophila cause epithelial hyperplasia in all imaginal discs. By contrast, mutations in the vestigial (vg) gene adversely affect cell viability in the wing imaginal discs and consequently cause loss of pattern in the adult wings. However, combining homozygous lgd or ft mutations with homozygous vg1 increases the size of the wing imaginal discs and partially restores the bristle pattern in the wings of pharate adults. Comparable pattern restoration in vg1 wings is also induced by a newly isolated weak hypomorphic lgd3 allele. Further, mosaic analysis revealed that whereas lgd clones generated by the Minute technique display abnormal differentiation, those induced in a homozygous vg1 background exhibit autonomous restoration of wing pattern. These results suggest that pattern restoration in vg1 wings can serve as an assay for hyperplasia induced by mutations in Drosophila tumor suppressor genes.

Animals↗

Uterine rupture in association with alkaloidal ("crack") cocaine abuse.

The use of alkaloidal ("crack") cocaine in pregnancy can result in systemic and focal vasoconstriction and abnormal uterine contractions forceful enough to cause the complete rupture of a gravid uterus along a previous vertical cesarean section scar. A 43-year-old woman was admitted to the emergency department with acute abdominal pain at 34 weeks' gestation. She had had a low vertical cesarean section 3 years previously for breech presentation with acute fetal distress at 28 weeks' gestation. The patient had a history of heavy "crack" abuse and admitted to inhaling "crack" throughout the day until 4 hours before admission. Within 15 minutes after presentation a laparotomy was performed, revealing an infant floating in the abdominal cavity. A live baby was promptly delivered, and the ruptured uterus was repaired. The patient was discharged 4 days post partum. "Crack" cocaine, through its known effects on the vasculature and contractility of the myometrium, likely facilitated the uterine rupture in this patient. The edges of the rupture wound were surprisingly clean, with little bleeding, perhaps owing to the drug's vasoconstrictive effects. It was therefore feasible to repair the uterus as an alternative approach to hysterectomy.

Adult↗

Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing.

We have exploited "progeny testing" to map quantitative trait loci (QTL) underlying the genetic variation of milk production in a selected dairy cattle population. A total of 1,518 sires, with progeny tests based on the milking performances of > 150,000 daughters jointly, was genotyped for 159 autosomal microsatellites bracketing 1645 centimorgan or approximately two thirds of the bovine genome. Using a maximum likelihood multilocus linkage analysis accounting for variance heterogeneity of the phenotypes, we identified five chromosomes giving very strong evidence (LOD score > or = 3) for the presence of a QTL controlling milk production: chromosomes 1, 6, 9, 10 and 20. These findings demonstrate that loci with considerable effects on milk production are still segregating in highly selected populations and pave the way toward marker-assisted selection in dairy cattle breeding.

Animals↗

Correlation of 24-hr esophageal pH patterns with clinical features and endoscopy in gastroesophageal reflux disease.

We performed 24-hr ambulatory esophageal pH monitoring in north Indian patients with gastroesophageal reflux disease (GERD) and correlated it with symptom severity and endoscopic abnormalities. Thirty-six consecutive patients with symptomatic GERD and 16 healthy volunteers underwent objective grading of clinical symptoms and endoscopic findings. Total, supine, and upright reflux periods as well as frequency and duration of reflux episodes were determined from the 24-h pH-metry record using standard software. This was abnormal in 32 patients, who could be categorized into upright refluxers (31.2%), supine refluxers (34.4%), and combined refluxers (34.4%). Supine reflux and upright reflux were distinct entities that did not correlate with each other (r = 0.22, P = NS). In upright refluxers, symptoms (P < 0.02) and endoscopic abnormalities (P < 0.005) were milder than in combined refluxers. Total duration of acid exposure correlated significantly with severity of symptoms (P < 0.001) and endoscopic esophagitis (P < 0.005). Patients with GERD had three distinct patterns of abnormal gastroesophageal reflux, with upright refluxers having milder disease and supine and combined refluxers having more severe disease. This may reflect differences in underlying mechanisms of reflux.

Adult↗

Microsatellite mapping of the gene causing weaver disease in cattle will allow the study of an associated quantitative trait locus.

A genetic disease in cattle, progressive degenerative myeloencephalopathy (weaver disease), is associated with increased milk production. This association could result from population stratification, from a pleiotropic effect of a single gene, or from linkage disequilibrium between the gene causing weaver disease and a quantitative trait locus (QTL) for milk production. To test these hypotheses, we performed an extensive linkage study in a bovine pedigree segregating for the weaver condition and identified a microsatellite locus (TGLA116) closely linked to the weaver gene (zmax, 8.15; theta, 0.03). TGLA116 and, by extension, the weaver locus were assigned to bovine synteny group 13. This microsatellite can be used to identify weaver carriers, to select against this genetic defect, and to study the effect of the corresponding chromosomal region on milk production in Brown Swiss and other breeds of cattle.

Animals↗

Characterisation and epitope analysis of monoclonal antibodies to virions of clover yellow vein and Johnsongrass mosaic potyviruses.

Mouse monoclonal antibodies (MAbs) against the Australian B strain of clover yellow vein (ClYVV-B) and the JG strain of Johnsongrass mosaic (JGMV) potyviruses were produced, characterised and the epitopes with which they reacted were deduced. Using intact particles of ClYVV a total of ten MAbs were obtained which reacted strongly with ClYVV-B in an enzyme-linked immunosorbent assay and Western blots. Four of these MAbs (1, 2, 4, and 13) were found to be ClYVV-specific, as they reacted with all five ClYVV strains from Australia and the U.S.A. but not with 11 strains of bean yellow mosaic (BYMV), pea mosaic (PMV), and white lupin mosaic (WLMV) viruses which, together with ClYVV, form the BYMV subgroup of potyvirses. These MAbs failed to react with eight other potyvirus species, including six which infect legumes like the viruses in the BYMV subgroup. The ClYVV MAb 10 was found to be BYMV subgroup-specific. It reacted strongly with 15 of the 16 strains of viruses in the subgroup and gave no reaction with eight other potyviruses. The other five ClYVV MAbs reacted with varying degrees of specificity with the BYMV subgroup viruses and also with other potyviruses. Eight of the ClYVV MAbs (1, 2, 4, 5, 13, 17, 21, and 22) reacted with the intact coat proteins only and not with the truncated (minus amino terminus) coat protein of ClYVV suggesting that the epitopes for these MAbs are located in the surface-exposed, amino-terminal region of the ClYVV coat protein. Comparison of published coat protein sequences of BYMV and ClYVV isolates indicated that the epitopes for the four ClYVV-specific MAbs may be in the amino-terminal region spanning amino acid residues 18 to 30, whereas those for the other four MAbs may be located in the first 17 amino-terminal amino acid residue region. The epitopes that reacted with BYMV subgroup-specific MAb 10 and MAb 30 which reacted with 20 of the 24 potyvirus isolates, are probably located in the core region of ClYVV coat protein as these MAbs reacted with the intact as well as truncated coat protein of ClYVV. Analysis, in Western blot immunoassay, of 17 MAbs raised against virions of JGMV revealed that only two MAbs (1-25 and 4-30) were JGMV-specific, whereas others displayed varying degrees of specificity to different potyviruses.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Microsatellite mapping of a gene affecting horn development in Bos taurus.

The presence or absence of horns in Bos taurus is thought to be under the genetic control of the autosomal polled locus, characterized by two alleles: P dominant over p, and causing the polled or hornless phenotype. We have demonstrated genetic linkage between the polled locus and two microsatellite markers, GMPOLL-1 and GMPOLL-2, and have assigned the corresponding linkage group to bovine chromosome 1. This confirms the existence of the postulated polled locus and the hypothesized inheritance pattern. It will allow marker assisted selection for the polledness trait in breeding programs and is a first step towards positional cloning and molecular study of a gene that has been subjected to both natural and artificial selection.

Alleles↗