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Biomedical subjects

M Sinha

Publications and source records attributed to M Sinha.

At least 19 recordsLinked to original sources
PubMed2006

Septic arthritis of the small joints of the hand.

Twenty-five patients with sepsis of 26 hand joints were treated by urgent debridement, antibiotics and early hand therapy. We reviewed 15 patients (16 joints) in a clinic and three patients by postal questionnaire after a mean follow-up of 54 (range 10-94) months. Of the 26 involved joints, 14 had restricted motion at discharge. Stiffness increased with increase in delay between onset and treatment. At final review, one joint with painful degenerative changes had been fused. Seven patients had regained full movements. The remaining six had some stiffness but, nevertheless, had undergone significant improvement in the ranges of movement. There were two cases with radiological joint degeneration in this group of six patients. Three patients had mild, intermittent pain. No patient had significant disability. While there is significant loss of motion after this joint pathology in the early recovery period, overall motion and function appears to improve over the longer term.

Activities of Daily Living↗
PubMed2004

Does failure to visualize the ureter distal to an impacted calculus constitute an impediment to successful lithotripsy?

BACKGROUND: A severe degree of ureteral obstruction is viewed as a predictor of poor outcome in shockwave lithotripsy (SWL). Impacted stones are often considered a contraindication to in-situ SWL. PATIENTS AND METHODS: Impaction in our study was defined as failure to visualize the ureter distal to the calculus with proximal hold-up of contrast for as long as 3 hours on an intravenous urogram (IVU). We evaluated 30 patients with impacted ureteral calculi, who were compared with a second unimpacted group matched for stone size and stone location. The calculi were reorganized into < or =10-mm and >10-mm groups. The results were compared in terms of clearance rates, number of shockwaves, number of sessions, and number of days between the start of SWL and clearance. RESULTS: Between January 1998 and December 2001, 30 impacted stones were treated with lithotripsy. Complete clearance rates in the impacted as well as the non-impacted group were 76.7%. There was no statistical difference in the number of shockwaves, sessions, or time to clearance. The results were poorer in lower-ureteral than upper-ureteral calculi, but this difference did not reach statistical significance. However, the differences between the < or =10-mm and >10-mm stones were statistically significant. CONCLUSION: Impaction on an IVU does not affect the results of lithotripsy.

Humans↗
PubMed2003

Outcome following a second hip fracture.

Hip fracture has a significant impact on medical resources and patient morbidity and mortality. Few patients admitted with a hip fracture are considered for prophylactic measures aimed at the reduction of further fracture risk. Currently, 10-13% of patients will later sustain a second hip fracture. In considering the possible role of prophylactic measures in the prevention of second hip fracture, we investigated whether second hip fracture has a significant further impact on patients' mobility and social independence. We also sought to identify a pattern to second hip fracture that may allow targeting of those patients who are most likely to benefit from currently available prophylactic measures. We undertook a retrospective review of 49 consecutive patients admitted with a second hip fracture between August 1999 and September 2000. Fewer patients maintained their ability to walk independently after the second fracture than did so after the first (53 and 91% respectively, P<0.0005). Following second hip fracture, patients' level of mobility determined their future social independence. Older patients and those with a history of multiple falls had a shorter time interval between fractures. Second hip fracture has a significant further impact on patients' mobility and social independence. Younger patients and those without a history of multiple falls are most likely to benefit from medical prophylaxis.

Aged↗
PubMed2001

Full-length cDNAs: more than just reaching the ends.

The development of functional genomic resources is essential to understand and utilize information generated from genome sequencing projects. Central to the development of this technology is the creation of high-quality cDNA resources and improved technologies for analyzing coding and noncoding mRNA sequences. The isolation and mapping of cDNAs is an entrée to characterizing the information that is of significant biological relevance in the genome of an organism. However, a bottleneck is often encountered when attempting to bring to full-length (or at least full-coding) a number of incomplete cDNAs in parallel, since this involves the nonsystematic, time consuming, and labor-intensive iterative screening of a number of cDNA libraries of variable quality and/or directed strategies to process individual clones (e.g., 5' rapid amplification of cDNA ends). Here, we review the current state of the art in cDNA library generation, as well as present an analysis of the different steps involved in cDNA library generation.

Automation↗
PubMed2001

The glucocorticoid inhibition of LFA-1 and CD2 expression by human mononuclear cells is reversed by IL-2, IL-7 and IL-15.

Glucocorticoids are agents endowed with powerful immunosuppressive and anti-inflammatory properties partially related to the inhibition of adhesion-related processes. We have previously demonstrated that glucocorticoids inhibit LFA-1 and CD2 expression in human peripheral blood mononuclear cells (PBMC) by down-regulating mRNA steady-state levels. In this study, we investigated whether glucocorticoids could also act indirectly by modulating the effect/function of cytokines whose expression are known to inhibit. To test this hypothesis, we replenished the following cytokines IL-2, IL-7, IL-15, TNF-alpha, IL-1beta, IL-4 and IL-10, in an in vitro PBMC culture system. Our results indicate that only the IL-2Rgamma-chain-dependent cytokines IL-2, IL-7 and IL-15, among the cytokines of this panel, could reverse the inhibition of glucocorticoids on PBMC adhesion molecule expression and the related functions of intercellular aggregation and proliferation. Furthermore, we also demonstrated that IL-2, IL-7 and IL-15 could induce de novo the synthesis of LFA-1 and CD2. Taken together, these data suggest that glucocorticoids inhibit PBMC LFA-1 and CD2 expression not only directly by modulating transcriptional events, but also indirectly through the inhibition of IL-2Rgamma-dependent cytokines.

CD2 Antigens↗
PubMed2001

Reinfusion of drained blood as an alternative to homologous blood transfusion after total knee replacement.

In patients undergoing total knee replacement we carried out a longitudinal cohort study to determine the efficacy and safety of a postoperative autologous blood reinfusion system, as an alternative to homologous, banked blood transfusions. Fifty patients received reinfusion of unwashed, filtered, shed blood, supplemented with banked blood transfusions as required. A control group of 50 patients in whom standard suction drains were used received homologous blood transfusions as required. In the study group, the homologous blood requirement was reduced by 80%. There was no significant difference in the postoperative haemoglobin values between the two groups. None of the patients developed any adverse reactions after reinfusion.

Adult↗
PubMed2001

Artificial neural network predicts CT scan abnormalities in pediatric patients with closed head injury.

BACKGROUND: Artificial neural networks (ANNs) use nonlinear statistical modeling techniques to explore relationships in complex clinical situations. This study compared predictive ability of a trained ANN model to that of physician prediction of cranial computed tomographic (CT) scan abnormalities in children with head injury. METHODS: A prospective cohort of 351 patients who presented with head trauma and underwent CT scans were studied. All pertinent data on historical and demographic information, and clinical features were recorded. Emergency department physicians used clinical judgment to record pretest probability of abnormal CT scans for all patients prospectively. Similar data from a retrospective chart review of 382 patients with head injury in the immediate preceding year were collected and used to train the ANN. Data from the prospective study was used to validate the ANN, construct a logistic regression model, and compare physician prediction. RESULTS: Forty-five (12.9%) of 351 patients had abnormal CT scans. In predicting CT scan abnormality, the ANN model was more sensitive (82.2%) compared with physician prediction (62.2%). CONCLUSION: ANNs may serve as a useful aid for decision support for emergency physicians in predicting intracranial abnormalities in closed head injury.

Accidental Falls↗
PubMed2001

Isoforms of Na+, K+-ATPase in human prostate; specificity of expression and apical membrane polarization.

The cellular distribution of Na+, K+-ATPase subunit isoforms was mapped in the secretory epithelium of the human prostate gland by immunostaining with antibodies to the alpha and beta subunit isoforms of the enzyme. Immunolabeling of the alpha1, beta1 and beta2 isoforms was observed in the apical and lateral plasma membrane domains of prostatic epithelial cells in contrast to human kidney where the alpha1 and beta1 isoforms of Na+, K+-ATPase were localized in the basolateral membrane of both proximal and distal convoluted tubules. Using immunohistochemistry and PCR we found no evidence of Na+, K+-ATPase alpha2 and alpha3 isoform expression suggesting that prostatic Na+, K+-ATPase consists of alpha1/beta1 and alpha1/beta2 isozymes. Our immunohistochemical findings are consistent with previously proposed models placing prostatic Na+, K+-ATPase in the apical plasma membrane domain. Abundant expression of Na+, K+-ATPase in epithelial cells lining tubulo-alveoli in the human prostate gland confirms previous conclusions drawn from biochemical, pharmacological and physiological data and provides further evidence for the critical role of this enzyme in prostatic cell physiology and ion homeostasis. Na+, K+-ATPase most likely maintains an inwardly directed Na+ gradient essential for nutrient uptake and active citrate secretion by prostatic epithelial cells. Na+, K+-ATPase may also regulate lumenal Na+ and K+, major counter-ions for citrate.

Aged↗
PubMed2000

Cost effectiveness analysis of different strategies of management of chronic hepatitis C infection in children.

BACKGROUND: Chronic hepatitis C virus infection in the pediatric patients is commonly encountered by clinicians, and although interferon-based therapy has been shown to be reasonably effective in children no formal economic analysis of such treatment strategies is available. METHODS: With a Markov cycle tree simulation model, a cost effectiveness analysis was done to compare interferon-based treatment strategies for chronic HCV infection in children with a strategy of no treatment in a cohort of 10-year-old otherwise healthy children. Clinical probabilities used in the model was obtained from available literature, and cost estimates were obtained from two teaching hospitals. Cost per patient, quality-adjusted life years gained in each strategy and incremental cost-effective ratio were the primary outcome measures compared. RESULTS: In the baseline analysis the treatment strategies dominated the strategy of no treatment. A 12-month treatment strategy was better than the 6-month treatment strategy. Combination therapy for 6 months with interferon and ribavirin was at least equally if not more effective than 12-month monotherapy. All treatment strategies decreased the number of patients developing decompensated cirrhosis, hepatocellular carcinoma and also number of orthotopic liver transplants in the lifetime of the model cohort. CONCLUSIONS: Interferon-based treatment strategies were more effective in terms of quality-adjusted life years saved and at the same time cheaper when compared with the strategy of no treatment. Combination therapy may be more cost-effective than interferon monotherapy, and clinical trials of combination therapy in pediatric patients are needed.

Child↗
PubMed2000

Protein kinase C modulates insulin action in human skeletal muscle.

There is good evidence from cell lines and rodents that elevated protein kinase C (PKC) overexpression/activity causes insulin resistance. Therefore, the present study determined the effects of PKC activation/inhibition on insulin-mediated glucose transport in incubated human skeletal muscle and primary adipocytes to discern a potential role for PKC in insulin action. Rectus abdominus muscle strips or adipocytes from obese, insulin-resistant, and insulin-sensitive patients were incubated in vitro under basal and insulin (100 nM)-stimulated conditions in the presence of GF 109203X (GF), a PKC inhibitor, or 12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), a PKC activator. PKC inhibition had no effect on basal glucose transport. GF increased (P < 0.05) insulin-stimulated 2-deoxyglucose (2-DOG) transport approximately twofold above basal. GF plus insulin also increased (P < 0.05) insulin receptor tyrosine phosphorylation 48% and phosphatidylinositol 3-kinase (PI 3-kinase) activity approximately 50% (P < 0.05) vs. insulin treatment alone. Similar results for GF on glucose uptake were observed in human primary adipocytes. Further support for the hypothesis that elevated PKC activity is related to insulin resistance comes from the finding that PKC activation by dPPA was associated with a 40% decrease (P < 0.05) in insulin-stimulated 2-DOG transport. Incubation of insulin-sensitive muscles with GF also resulted in enhanced insulin action ( approximately 3-fold above basal). These data demonstrate that certain PKC inhibitors augment insulin-mediated glucose uptake and suggest that PKC may modulate insulin action in human skeletal muscle.

Abdominal Muscles↗
PubMed2000

Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia.

Interleukin (IL)-6 reportedly has negative inotropic and hypertrophic effects on the heart. Here, we describe endotoxin-induced IL-6 in the heart that has not previously been well characterized. An intraperitoneal injection of a bacterial lipopolysaccharide into C57BL/6 mice induced IL-6 mRNA in the heart more strongly than in any other tissue examined. Induction of mRNA for two proinflammatory cytokines, IL-1beta and tumor necrosis factor (TNF)-alpha, occurred rapidly before the induction of IL-6 mRNA and protein. Although stimulation of isolated rat neonatal myocardial cells with IL-1beta or TNF-alpha induced IL-6 mRNA in vitro, nonmyocardial heart cells produced higher levels of IL-6 mRNA upon stimulation with IL-1beta. In situ hybridization and immunohistochemical analyses localized the IL-6 expression primarily in nonmyocardial cells in vivo. Endotoxin-induced expression of cardiac IL-1beta, TNF-alpha, and intercellular adhesion molecule 1 was augmented in IL-6-deficient mice compared with control mice. Thus cardiac IL-6, expressed mainly by nonmyocardial cells via IL-1beta action during endotoxemia, is likely to suppress expression of proinflammatory mediators and to regulate itself via a negative feedback mechanism.

Animals↗
PubMed1999

Induction of the alpha(1)-antichymotrypsin gene in the brain associated with TGF-beta1 deficiency or systemic administration of endotoxin.

We report that mRNA levels for alpha(1)-antichymotrypsin (ACT), a component of beta-amyloid plaques in Alzheimer's disease, are significantly increased in the brains of two different mouse models that develop inflammation: (1) acute inflammation caused by intraperitoneal injection with lipopolysaccharide (LPS) and (2) chronic inflammation in knockout mice lacking the anti-inflammatory cytokine transforming growth factor beta1 (TGF-beta1). While brain mRNA levels for the inflammatory cytokines TNFalpha, IL-1beta, and IL-6 were all elevated in the LPS-injected mice, only the mRNA for IL-1beta increased significantly in TGF-beta1-deficient mice. The transcription factor C/EBPbeta was strongly activated in the brains of both models. These results support the hypothesis that, through induction of the ACT gene in the brain, inflammation plays an important role during the development of Alzheimer's disease and that IL-1beta and C/EBPbeta may be involved in this process.

Animals↗
PubMed1999

Sequencing and exon mapping of the inositol 1,4,5-trisphosphate receptor cDNA from Drosophila embryos suggests the presence of differentially regulated forms of RNA and protein.

A single gene appears to code for the inositol 1,4,5-trisphosphate receptor (itpr) in Drosophila melanogaster, as compared to three known genes in mammals. Expression of the itpr gene in Drosophila occurs in a wide range of tissues and developmental stages, suggesting its requirement during diverse cellular and physiological processes. A head cDNA for the Drosophila IP3R has previously been cloned and sequenced. Here we present and analyse the sequence of cDNAs encoding the complete IP3R, obtained from embryonic stages. The embryonic cDNA is 10525bp long and is a splice variant of the head cDNA. It differs from the latter in three main respects. It has longer 5' and 3' untranslated regions, two potential casein kinase II sites are missing in the embryo form and it contains an alternate exon which results in the replacement of three residues (VHF) in the head form by five residues (GVGHSV) in the embryo form. The significance of these changes is discussed. An exon-intron map of the gene derived from sequencing of intron-containing genomic fragments is also presented. The gene has a total of 11 introns, of which more than half are clustered in a region of the modulatory domain of the IP3R.

Animals↗
PubMed1999

Remodeling of forearm fractures in children.

A prospective study of 42 children with forearm fractures, treated by closed reduction and plaster, was conducted to assess the remodeling capacity of the radial epiphyseal plate after union of fracture with angulation. The children's ages ranged from 3 to 15 years. The effect of residual angulation of the healed fracture on the distal radial epiphyseal plate was examined radiographically over a median follow-up time of 3 years and 2 months, to observe the behavior of the distal radial epiphyseal plate during remodeling and to identify the factors that influenced this process. On the basis of these findings, guidelines are proposed for the treatment of forearm fractures that have healed with residual angulation. The inclinations of the distal radial epiphyseal plate on the fractured and normal forearms were compared on anteroposterior and lateral radiographs, at union and at final follow-up, in both the radioulnar and the dorsovolar planes. An alteration of inclination was seen in all patients with dorsovolar angulation of the radial growth plate, which always tended toward a correction of the abnormal inclination. In diaphyseal fractures, the distal radial epiphyseal plate realigned well only in children aged < or = 10 years, whereas with distal radial fractures, realignment of the epiphyseal plate and restoration of function was uniformly good up to age 15. Diaphyseal fractures, with radioulnar angulation in the growth plate, did not seem to remodel completely and were associated with loss of motion, whereas in distal fractures, irrespective of the final inclination of the epiphyseal plate, the range of motion returned completely at the end of follow-up. Abnormal angulation in the radioulnar plane was poorly corrected in all patients. These results could be helpful in the treatment of forearm fractures that are positioned or have healed in residual angulation.

Adolescent↗
PubMed1998

Conversion of dengue virus replicative form RNA (RF) to replicative intermediate (RI) by nonstructural proteins NS-5 and NS-3.

Dengue viruses infect more than 100 million people each year and cause serious clinical manifestations. It is important to understand the replication of these viruses so that therapeutic and/or prophylactic agents may be designed. Dengue virus type 2 nonstructural proteins NS-5 and NS-3 were produced by in vitro transcription and translation of cloned genes. Both proteins possessed RNA-dependent RNA polymerase activity as measured by their ability to convert purified replicative form (RF) RNA to replicative intermediate (RI). The recombinant proteins, however, required one or more cellular protein(s) for their activity. Examination of NS-3 protein sequence revealed heretofore unnoticed sequence similarities with other polymerases.

Amino Acid Sequence↗