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Biomedical subjects

P Bansal

Publications and source records attributed to P Bansal.

At least 19 recordsLinked to original sources

Oral quinolones in hospitalized patients: an evaluation of a computerized decision support intervention.

OBJECTIVE: To determine whether a computerized decision support system could increase the proportion of oral quinolone antibiotic orders placed for hospitalized patients. DESIGN: Prospective, interrupted time-series analysis. SETTING: University hospital in the south-eastern United States. SUBJECTS: Inpatient quinolone orders placed from 1 February 2001 to 31 January 2003. INTERVENTION: A web-based intervention was deployed as part of an existing order entry system at a university hospital on 5 February 2002. Based on an automated query of active medication and diet orders, some users ordering intravenous quinolones were presented with a suggestion to consider choosing an oral formulation. MAIN OUTCOME MEASURE: The proportion of inpatient quinolone orders placed for oral formulations before and after deployment of the intervention. RESULTS: There were a total of 15 194 quinolone orders during the study period, of which 8962 (59%) were for oral forms. Orders for oral quinolones increased from 4202 (56%) before the intervention to 4760 (62%) after, without a change in total orders. In the time-series analysis, there was an overall 5.6% increase (95% CI 2.8-8.4%; P < 0.001) in weekly oral quinolone orders due to the intervention, with the greatest effect on nonintensive care medical units. CONCLUSIONS: A web-based intervention was able to increase oral quinolone orders in hospitalized patients. This is one of the first studies to demonstrate a significant effect of a computerized intervention on dosing route within an antibiotic class. This model could be applied to other antibiotics or other drug classes with good oral bioavailability.

Administration, Oral↗

Substitution urethroplasty for anterior urethral strictures: a critical appraisal of various techniques.

OBJECTIVE: To retrospectively compare the outcome of various techniques of substitution urethroplasty. PATIENTS AND METHODS: Between 1989 and 2000, 109 patients (mean age 39.5 years) underwent substitution urethroplasty for recurrent anterior urethral strictures. Between 1989 and 1995 the procedure was by ventral placement of free grafts (bladder mucosa, buccal mucosa, penile skin) or penile skin flaps. From 1995 onwards the flaps and grafts (buccal mucosa) were applied either ventrally or dorsally. Stricture recurrence and the complications associated with each technique were compared. RESULTS: Ventral onlay repairs were associated with a higher incidence of complications than dorsal repairs, e.g. postvoid dribbling (39% vs 23%, P = 0.01), ejaculatory dysfunction (20% vs 5%, P = 0.03) and flap/graft pseudo-diverticulum or out-pouching (26% vs 2.6%, P = 0.01). Superficial penile skin necrosis was significantly more common with the use of penile skin flaps than with free grafts. There was no significant difference in stricture recurrence, erectile dysfunction and residual penile deformity among the various techniques. CONCLUSIONS: Dorsal free graft/flap onlay urethroplasty gives better results than ventrally placed free grafts/flaps. Dorsal onlay buccal mucosal urethroplasty is a versatile procedure and associated with fewer complications than other substitution methods.

Adolescent↗

Diagnosing the acutely locked knee.

A prospective cross-sectional study was undertaken to observe the management of acutely locked knees and identify features predictive of causes remediable by surgical intervention. A total of 50 consecutive patients presented for orthopaedic opinion with an acutely locked knee. In all, 48 underwent examination and arthroscopy under general anaesthesia. Among them, 43 were found to have distinct pathology causing a mechanical block to full extension. Four were found to have only degenerative changes, two "unlocked" without any surgical intervention, and one was entirely normal. A mechanical cause of the "locked" knee can be identified consistently using three key components from the history and examination: a history of a definite injury, localised joint line tenderness and the presence of an effusion. The use of such criteria would assist in the prompt, appropriate triage and referral of patients with an acutely locked knee.

Acute Disease↗

Sequential anastomosis of accessory renal artery to inferior epigastric artery in the management of multiple arteries in live related renal transplantation: a critical appraisal.

In live related renal transplant program, management of multiple renal arteries (MRA) is technically demanding and used to be considered a relative contraindication because of increased risk of vascular and urologic complications. We present a retrospective analysis of the outcome of grafts with MRA and suggest certain guidelines. Of the 680 live related kidney transplantations done, 53 allografts had MRA. Cases were grouped according to the reconstruction technique: group A, MRA reconstructed ex vivo into a single renal artery (n=27); group B, MRA with multiple anastomoses in vivo (n =13); group C, MRA with sequential revascularization using inferior epigastric artery (n=11). We compared serum creatinine, acute tubular necrosis, rejection rates and the rewarm ischemia time between the three groups. Overall patient survival and graft survival were excellent (100 and 96%). Mean serum creatinine at 1 yr did not differ significantly between the three groups. Rewarm ischemia time was significantly less in group C (p<0.01). Incidence of acute tubular necrosis and rejection episodes was also less in group C although the difference was statistically significant only between group C and group B. We conclude that allografts with MRA can be used successfully in a live related renal transplantation program. Bench reconstruction should be done whenever possible. For reconstruction of an accessory vessel, inferior epigastric artery with sequential revascularization is recommended.

Adolescent↗

T cells in mice expressing a transgenic human TCR beta chain get positively selected but cannot be activated in the periphery by signaling through TCR.

TCR-CD3 complex-mediated signaling is crucial for both developmental selection and antigenic activation of T cells. We report that mice expressing a recombined human TCRbeta chain (Tg), which have normal development of T cells, mounted very weak responses to immunization with protein antigens as well as the HA307-319 peptide recognized by the human T cell clone HA1.7 from which the transgene is derived. An anti-CD3epsilon mAb triggered equivalent proliferation from Tg and non-Tg T cells, but an anti-human TCRbeta mAb induced proliferation poorly in Tg T cells in contrast to human T cells or HA1.7. In Tg mice, T cells expressing endogenous TCR were CD44(high), whereas most transgene-expressing T cells remained CD44(low), suggesting that transgene-expressing cells are not activated in the periphery to participate in immune responses. However, anti-human TCRbeta could induce some activation markers on T cells and cross-linking of the Tg TCR by plate-coated anti-human TCRbeta efficiently induced T cell proliferation. Human TCRbeta-mediated Tg T cell activation could be rescued by exogenous IL-2, as well as by the calcium ionophore A23187, but not by phorbol esters. Thus, this human TCRbeta chain functions efficiently for positive selection of mouse T cells, but not for their peripheral activation, probably because of a lack of oligomerization leading to defects in signaling for calcium flux and IL-2 induction. The data thus suggest an early point of separation of signaling pathways between positive selection and peripheral activation of T cells.

Animals↗

A computer based intervention on the appropriate use of arterial blood gas.

OBJECTIVE: To evaluate impact of a computer-based intervention on arterial blood gas (ABG) usage in an intensive care setting. DESIGN: Retrospectively examined, via mixed group analysis, the effects of the intervention on ABG usage in the intensive care unit (ICU). SUBJECTS: Included all clinicians who placed ABG orders in an ICU using the computerized physician order-entry system, as well as controls in non-order entry units. METHODS: Computer-based intervention presenting ordering clinician with patient s previous ABG values and limiting forward duration of tests ordered. Study spanned 12 weeks, 5 weeks pre-intervention and 7-weeks post-intervention. Of 8 ICUs, intervention implemented in 6, not implemented in 2. Data analyzed using the repeated measure ANOVA. RESULTS: Physicians entered <40% ABG orders. 376 ABGs per week processed pre-intervention, 387 per week post. Results nonsignificant with a p= 0.09. Orders placed declined from 1039 per week, Jan 2000 to 662 per week, April 2001. DISCUSSION: Study did not demonstrate significant change; limited power. Need longer study periods. Impact improved in the future by targeting physician users and tailoring intervention to specific work flow pattern of high utilization units.

Analysis of Variance↗

Comparative anti-nociceptive, anti-inflammatory and toxicity profile of nimesulide vs nimesulide and piperine combination.

Piperine is an inhibitor of various hepatic and other enzymes involved in the biotransformation of drugs. Preliminary pharmacokinetic studies conducted by us suggested the increased bioavailability of nimesulide co-administered with piperine. The present study was, thus, conducted to evaluate the antinociceptive, anti-inflammatory and toxicity profile of a new nimesulide-piperine combination administered orally as compared with nimesulide alone. Antinociceptive efficacy was tested using an acetic acid writhing test and tail flick latency test (TFL). The ED50 value of a nimesulide-piperine combination in writhing test was calculated to be significantly lower (1.5 mg kg(-1)) as compared to (11.2 mg kg(-1)) of nimesulide alone. The antinociceptive effect was lesser in the tail flick latency test as compared to what was observed in the writhing test indicating the peripheral action of the Non-Steriodal Anti-Inflammatory Drug (NSAID). In carrageenan-induced inflammatory tests, the nimesulide-piperine combination was found to be dose-to-dose superior than nimesulide alone. Acute toxicity studies on mice revealed a reduction in lethal dose (LD50) of the combination (980 mg kg(-1)) as compared to nimesulide (1500 mg kg(-1)) alone. Results from the present study suggest a better therapeutic index for the nimesulide-piperine combination indicating that this combination would further reduce the frequency of adverse effects associated with nimesulide alone.

Administration, Oral↗

MHC class I-restricted presentation of maleylated protein binding to scavenger receptors.

Pathways for loading exogenous protein-derived peptides on MHC class I are thought to be present mainly in monocyte-lineage cells and to involve phagocytosis- or macropinocytosis-mediated antigenic leakage into either cytosol or extracellular milieu to give peptide access to MHC class I. We show that maleylation of OVA enhanced its presentation to an OVA-specific MHC class I-restricted T cell line by both macrophages and B cells. This enhanced presentation involved uptake through receptors of scavenger receptor (SR)-like ligand specificity, was TAP-1-independent, and was inhibited by low levels (2 mM) of ammonium chloride. No peptide loading of bystander APCs by maleylated (maleyl) OVA-pulsed macrophages was detected. Demaleylated maleyl-OVA showed enhanced MHC class I-restricted presentation through receptor-mediated uptake and remained highly sensitive to 2 mM ammonium chloride. However, if receptor binding of maleyl-OVA was inhibited by maleylated BSA, the residual presentation was relatively resistant to 2 mM ammonium chloride. Maleyl-OVA directly introduced into the cytosol via osmotic lysis of pinosomes was poorly presented, confirming that receptor-mediated presentation of exogenous maleyl-OVA was unlikely to involve a cytosolic pathway. Demaleylated maleyl-OVA was well presented as a cytosolic Ag, consistent with the dependence of cytosolic processing on protein ubiquitination. Thus, receptor-specific delivery of exogenous protein Ags to APCs can result in enhanced MHC class I-restricted presentation, suggesting that the exogenous pathway of peptide loading for MHC class I may be a constitutive property dependent mainly on the quantity of Ag taken up by APCs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Expression of an immunoglobulin heavy chain transgene in macrophage as well as lymphocyte lineages in vivo.

A rearranged immunoglobulin heavy chain (IgH) transgene-encoded protein is expressed in macrophage lineage cells, in addition to B and T lineages, in transgenic mouse bone marrow. Peripheral macrophages also express transgenic IgH protein. Mature T cells express lower levels than immature thymocytes. Almost all B220+ cells in the bone marrow express transgenic IgH protein, and this early expression in the B lineage is accompanied by a reduction of cell frequency even in the early B220+ CD43+ BP-1- stages, although it is more prominent in BP-1+ pre-B cells. Thus, an IgH transgene can be expressed not only in lymphoid but also in myeloid cells, although its developmental effects are restricted to the B cell lineage.

Animals↗

A placenta-derived suppressor factor with a T-cell bias.

PROBLEM: Functional and mechanistic aspects of immunosuppression by murine placental supernatants (MPS) were investigated. METHOD OF STUDY: MPS and a low molecular weight fraction of the supernatant (MPSf) were tested for suppressive action on T-cell reactivity in vitro and in vivo, on B-cell responses and on T-cell activation events. RESULTS: MPS and MPSf suppress mitogen-induced proliferation and mixed lymphocyte reactions of human and murine lymphocytes, antigen-induced proliferation of T cells in vitro and in vivo, proliferation of CD8+ lymphocytes, proliferation induced by cross-linking of surface CD3 and the in vivo response of mice to allogeneic stimuli. MPSf affects cell cycling of activated T cells and blocks interleukin (IL)-2 production. MPSf does not affect antibody production or the induction of MHC class II expression on B cells. CONCLUSIONS: MPSf is a potent inhibitor of T-cell responses in vitro and in vivo, with no demonstrable effect on B-cell function.

Animals↗

Presence of activated antigen-binding B cells during immunization enhances relative levels of IFN-gamma in T cell responses.

To examine the influence of Ag presentation by B cells on immune responses, we have used mice transgenic for an Ig heavy chain from a monoclonal anti-azobenzenearsonate (Ars) Ab to deliver Ag to B cells during immunization. A large proportion of transgene-expressing B cells in these mice binds Ars, while transgenic serum Ig shows poor Ars binding. Transgenic B cells present Ars proteins better than their nonhaptenated counterparts. This is associated with an increase in the proliferative responses of transgenic T cells to Ars protein immunization. Although B cell numbers in the transgenic mice are lower, many B cells in them show an activated phenotype, as identified by altered surface levels of peanut agglutinin reactivity, CD23, CD24, CD44, CD62L, and CD86. Even against nonhaptenated immunogens, transgenic responses show significant enhancement in the relative proportions of the Th1 cytokine IFN-gamma over the Th2 cytokines IL-4 and IL-10. Haptenated immunogens further enhance the predilection of transgenic mice to produce relatively more IFN-gamma. Consistent with this, there is an increase in IgG2a/IgG1 ratios in serum Abs in response to haptenated immunogens in transgenic mice. Adoptive transfer of primed hapten-specific secondary B cells into nontransgenic mice also induces an increase in relative levels of IFN-gamma in response to haptenated immunogens. Thus, presentation of immunogen in vivo by activated Ag-binding B cells contributes to enhanced immunogenicity and a Th1 cytokine bias.

Animals↗

Comorbid occurrence of cholelithiasis and gastrointestinal cancer.

OBJECTIVE: To test whether gallstone disease represents a general risk factor for gastrointestinal cancer. METHODS: The comorbid occurrences of cholelithiasis or choledocholithiasis with cancers of the biliary tract, pancreas, small and large intestine were analysed in a population of 3.41 million military veterans who were discharged from VA hospitals distributed throughout the USA between 1981 and 1993. Comorbidity was calculated as the ratio between the observed and expected number of hospitalized veterans with cholelithiasis plus cancer. A 95% confidence interval was calculated based on the Poisson distribution of the observed number of patients with comorbidity. RESULTS: In cholelithiasis, the ratio of comorbid occurrence with biliary cancer was 4.59 (4.06-5.31). In choledocholithiasis, the ratio of comorbid occurrence with biliary cancer was 9.31 (7.20-11.84) and with pancreatic cancer 4.34 (3.80-4.94). These ratios remained significant when the analyses were confined to cholelithiasis or choledocholithiasis documented before the first diagnosis of cancer. The ratios of the comorbid occurrences between cholelithiasis and cancers of the small or large intestine were only significant when total comorbid occurrences were analysed, but vanished in the analysis restricted to cholelithiasis or choledocholithiasis documented before the first diagnosis of cancer. CONCLUSION: The occurrence of gallstones represents a risk factor for pancreaticobiliary cancer, but not cancers involving other parts of the gastrointestinal tract. This association appears particularly strong in patients with choledocholithiasis.

Cholelithiasis↗

Risk factors of colorectal cancer in inflammatory bowel disease.

BACKGROUND: It is unknown whether colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) behaves differently from regular CRC in patients without IBD. A case-control study was conducted to compare CRC in patients with and without underlying IBD. METHODS: The Department of Veterans Affairs (VA) maintains a computerized file of all hospital discharges among U.S. military veterans since 1970. This file accrues the data of 1 million hospital discharges per year. All patients with IBD and all patients with CRC who had been discharged from a VA hospital between 1981 and 1993 were selected. The influence of various risk factors on the occurrence of CRC in IBD and its mortality in patients with and without IBD was tested by logistical regression analyses. RESULTS: Of the 11,446 subjects with IBD, 371 had colon cancer. CRC was diagnosed in 52,243 subjects without IBD. CRC patients with IBD were 7 yr younger than those without IBD, but in patients with Crohn's disease, more cancers were located in the proximal colon (chi 2 = 18.10, df = 5, p = 0.003). The occurrence of CRC in IBD was influenced by the following risk factors: age [odds ratio (OR) = 1.45, 95% confidence interval (CI) = 1.35-1.57], sclerosing cholangitis (OR) = 3.41, CI = 2.03-5.73), and history of a disease associated with consumption of nonsteroidal anti-inflammatory drugs (NSAID) (OR = 0.84, CI = 0.65-1.09). Sex, race, and type of IBD did not exert a significant influence on the development of cancer. Cancer-related mortality was influenced by the following risk factors: age (OR = 1.16, CI = 1.14-1.18), male gender (OR = 1.23, CI = 1.06-1.44), white race (OR) = 0.97, CI = 0.96-0.99), and history of NSAID consumption (OR = 0.68, CI = 0.65-0.72). Presence of IBD was not associated with a significant influence on CRC mortality (OR = 1.00, CI = 0.70-1.43). CONCLUSIONS: CRC affects IBD patients at a younger age and is characterized by a more proximal localization when compared with CRC of non-IBD patients. NSAID exert a protective influence against CRC in patients with IBD similarly as in patients without IBD. Sclerosing cholangitis is associated with a strong risk of developing colon cancer in patients with IBD.

Age Distribution↗

Pancreatitis is a risk factor for pancreatic cancer.

BACKGROUND & AIMS: The Department of Veterans Affairs (VA) maintains a computerized file of all hospital discharges since 1970. In taking advantage of this large database, the present study aimed to determine whether pancreatitis is a risk factor for pancreatic cancer. METHODS: A case control study compared the occurrence of pancreatitis in 2639 patients with pancreatic cancer and a matched control group of 7774 subjects using multivariate conditional logistic regression. RESULTS: The odds ratio associated with pancreatitis increased from 2.04 (95% confidence interval [CI], 1.53-2.72) 7 or more years before the first diagnosis of cancer to 2.14 (CI, 1.68-2.72) 3 or more years before cancer diagnosis and to 2.31 (CI, 1.87-2.86) 1 or more years before cancer diagnosis. In a multivariate analysis, all types of pancreatitis or chronic pancreatitis alone were associated with a significant risk, their odds ratios being 3.42 (CI, 1.98-5.91) and 2.23 (CI, 1.43-3.49), respectively. No influence was exerted by other variables, such as history of gallstone disease or alcoholism, frequency of hospital discharges with pancreatitis, and length of coverage in the VA system. CONCLUSIONS: A history of pancreatitis constitutes a significant risk for subsequent development of pancreatic cancer. The increase of the risk with decreasing time before the diagnosis of cancer may indicate that a fraction of pancreatic cancers are initially misdiagnosed as pancreatitis.

Adult↗

Immune responses to the capsular polysaccharide of Mycoplasma dispar in calves and mice.

Humoral and cell-mediated immune responses to the capsular polysaccharide (CPS) of M. dispar and polygalacturonic acid (pGaIU--a structurally similar polysaccharide) were investigated in calves experimentally infected with Mycoplasma dispar and in mice immunized with CPS or pGaIU. Sera, tracheobronchial lavage and nasal fluids, collected before and after infection in calves, were checked for the presence of anti-CPS and anti-pGaIU antibodies. The sera from mice injected with CPS or pGaIU were checked for different classes of anti-CPS and anti-pGaIU antibodies. Peripheral blood lymphocytes from calves and splenic lymphocytes from mice were monitored for specific proliferative responses to CPS and pGaIU. At about 2 weeks post-infection, anti-CPS IgM response in serum, anti-CPS and anti-pGaIU IgM and IgA response in lavage fluid and lymphocyte proliferative response was seen in the calves. Mice immunized with CPS and pGaIU gave exclusively IgM responses. No secondary response was seen in mice immunized with CPS in contrast to mice immunized with pGaIU. Antibodies cross-reactive with pGaIU were present in the sera of CPS-immunized mice but antibodies cross-reactive with CPS were not found in pGaIU-immunized mice. No significant blastogenic response was shown by mouse splenocytes to CPS or pGaIU.

Animals↗

Poly ADP ribosylation as a possible mechanism of microwave--biointeraction.

Electromagnetic fields (EMFs) affect the metabolism of the body including the nervous, endocrine, cardiovascular, hematological as well as the reproductive system. EMFs are environmental pollutants, thus posing a health hazard which can cause steric changes in the molecule located at the cell surface. Microwaves are known to cause chromosomal abberations and act as tumor promoters. The process involves a stream of signals from cell membrane to nucleus and other organelles. The present investigations aim to understand the mechanism of biological effects of microwaves (2.45 GHz). The effect was studied on poly ADP-ribosylation, which is a post translational modification of chromatin protein catalysed by the enzyme poly ADPR polymerase using NAD+ as the substrate. Poly ADP-ribosylation has been shown to be involved in several aspects of chromatin structure and function. Twenty-three days old rats weighing 42-48 gms were exposed at a microwave dose level of 1.0 mW/cm2. After exposure for sixty days the animals were sacrificed and an estimation of poly ADPR polymerase activity was undertaken in different organs of these animals. There was an increase of 20% in its activity in liver, 35% in testis, whereas brain showed a 53% decrease in diencephalon and 20% decrease in the cortex in the exposed animals as compared to their respective controls. There was no change in enzyme activity in spleen and kidney. This was accompanied by concomitant changes in NAD+ levels. The above results may be cited as important events in carcinogenesis and tumor promotion related to microwave exposure and the signal transduction mechanism involved. The goal is to shed light on complex ecogenetic interactions leading to cancer modulation of gene expression by epigenetic mechanism.

Animals↗