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Biomedical subjects

R Seshadri

Publications and source records attributed to R Seshadri.

At least 19 recordsLinked to original sources
PubMed2006

Weight loss and reduced body mass index: a critical issue in children with multiorgan chronic graft-versus-host disease.

Weight loss and malnutrition are major problems in patients with chronic graft-versus-host disease (GVHD). In adults, low body mass index (BMI) is a predictor for mortality; however, weight loss and BMI have not been studied in pediatric chronic GVHD. A retrospective study on 18 children with extensive chronic GVHD was completed. Median age at SCT was 12.3 (range 0.6-23) years; age at chronic GVHD diagnosis was 12.5 (1-23) years. Patients with multiorgan involvement had a mean maximal decrease in BMI of 20.9% and most dropped below 10th percentile in expected weight-for-age. This change in BMI not only indicates a significant decrease in weight but often a plateau in stature. In contrast, patients with one organ system involved had a mean maximal decrease in BMI of 5% and did not fall below 10th percentile. All patients with multiorgan involvement required salvage therapy beyond steroids and CSA. Three patients died due to complications of chronic GVHD. Weight loss and malnutrition (as reflected by a decrease in BMI) are clinically significant issues in children with multisystem chronic GVHD. Weight loss is likely another systemic manifestation of the disease and may contribute, along with other factors such as increased immunosuppression and infection, to increased mortality in this group.

Adolescent↗
PubMed2005

Why generic and disease-specific quality-of-life instruments should be used together for the evaluation of patients with persistent allergic rhinitis.

BACKGROUND: The importance of assessing health-related quality of life (HRQL) of patients with allergic rhinitis (AR) has been well established, but the specific roles of rhinitis-specific or general health instruments have not been delineated. OBJECTIVE: We analysed the psychometric properties of a disease-specific instrument, the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ) and the general health instrument, the Medical Outcome Short-Form 36 (SF-36) as they are employed in combination in patients with persistent AR in clinical practice. METHOD: We analysed the data collected from a prospective study of 43 newly diagnosed patients with persistent AR and 44 controls. We interviewed the patients four times, at baseline, weeks 4, 8 and 10. RESULTS: The RQLQ and SF-36 have good discriminative property, internal consistency, and test-retest reliability. The RQLQ is superior to the SF-36 as an evaluative instrument because more of its domains respond to change, the magnitude of change was greater, and the response was faster. The SF-36 is more susceptible to floor and ceiling effects. Both instruments are unsuitable for mildly symptomatic patients based on Rasch model analysis. Each questionnaire assesses a distinct and significant portion of the total HRQL of persistent AR. CONCLUSION: The SF-36 and RQLQ are good for discriminating rhinitis patients from controls, but the former is poor for detecting changes in QOL. Both are inappropriate for mildly symptomatic patients. Each instrument measures non-overlapping halves of the measurable HRQL. For an assessment of the HRQL in persistent AR that is complete and responsive both instruments should be employed together.

Adult↗
PubMed2004

Outcomes of unrelated cord blood transplants and allogeneic-related hematopoietic stem cell transplants in children with high-risk acute lymphocytic leukemia.

Acute lymphocytic leukemia (ALL) is a common indication for hematopoietic stem cell transplantation (HSCT) in children. Use of unrelated cord blood (UCB) has become increasingly popular as a stem cell source, given the rapid availability and decreased GVHD potential. Publications describing outcomes of children with leukemia who underwent UCB transplants have compared them to those having received unrelated donor marrow transplants. Results are similar. We compared our outcomes using UCB vs allogeneic-related hematopoietic stem cells in pediatric ALL patients since 1992. A total of 49 patients were analyzed. All patients were either in CR1 with high-risk features (n=21) or in CR2 (n=28) with initial remission less than 36 months. Patients received myeloablation with fractionated total body irradiation, cyclophosphamide, and etoposide and GVHD prophylaxis with cyclosporine and methotrexate. Antithymocyte globulin was added for UCB recipients to address the HLA differences. In all, 23 patients underwent allogeneic -related HSCT and 26 underwent UCB transplantation. Other than increased time to engraftment for UCB recipients, results are equivalent. The 3-year overall survival is 64% and 3-year event-free survival is 60% for both groups. Rates of GVHD and transplant-related mortality are also equivalent. UCB is a reasonable option for children with ALL who are referred for HSCT.

Adolescent↗
PubMed2003

Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus faecalis.

The complete genome sequence of Enterococcus faecalis V583, a vancomycin-resistant clinical isolate, revealed that more than a quarter of the genome consists of probable mobile or foreign DNA. One of the predicted mobile elements is a previously unknown vanB vancomycin-resistance conjugative transposon. Three plasmids were identified, including two pheromone-sensing conjugative plasmids, one encoding a previously undescribed pheromone inhibitor. The apparent propensity for the incorporation of mobile elements probably contributed to the rapid acquisition and dissemination of drug resistance in the enterococci.

Adhesins, Bacterial↗
PubMed2002

Frequency and genetic basis of MHC, beta-2-microglobulin and MEMO-1 loss of heterozygosity in sporadic breast cancer.

The Human Leukocyte Antigen (HLA) class I molecules are critical factors in T cell recognition of abnormal, including neoplastic, cells. Loss of HLA class I expression phenotypes, as defined by immunohistochemistry-based tests, have been previously described in many types of cancer. Here we describe a microsatellite marker DNA-based loss of heterozygosity (LOH) analysis of three distinct chromosomal regions which have been implicated in HLA class I expression on a cohort of 99 unselected sporadic breast cancer samples. These regions comprise the 4Mb major histocompatibility complex (MHC) region on chromosome 6p, which contains the HLA class I heavy chain loci and other genes responsible for antigen processing, the HLA class I light chain (beta-2-microglobulin, beta2m) gene on chromosome 15q, and the putative HLA class I modifier of methylation gene (MEMO-1) on chromosome 1p. Additional chromosome 6 markers were also employed to determine the likely genetic mechanism for MHC loss. We show that 25/99 (25%) of samples show allelic loss within the MHC, 28/95 informative samples (29%) show allelic loss of beta2m and 21/76 informative samples (28%) show allelic loss of MEMO-1. Approximately half of the samples are predicted to have compromised HLA class I gene expression due to LOH at one and/or other of these three loci. Sequencing of the remaining beta2m allele in samples displaying beta2m LOH failed to detect any additional intragenic mutations. Analysis of the frequency of samples showing LOH at either 0, 1, 2 or 3 of the genomic regions analyzed suggested clustering of tumors into either 'no loci loss' or '3 loci loss' categories. These results reveal major underlying genetic causes for the high level of HLA class I expression loss seen in breast cancer.

Breast Neoplasms↗
PubMed2001

Differential transduction efficiency of SCID-repopulating cells derived from umbilical cord blood and granulocyte colony-stimulating factor-mobilized peripheral blood.

The gene transfer efficiency into nonobese diabetic/severe combined immunodeficient (NOD/SCID)-repopulating cells (SRCs) derived from umbilical cord blood (UCB) (n = 11 NOD/SCID mice) and granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood (MPB) (n = 64 NOD/SCID mice) was compared using a clinically relevant protocol and a retrovirus vector expressing the enhanced green fluorescent protein (EGFP). At 6-9 weeks after transplantation, the frequency of transduced human cells in the bone marrow (BM) (40.5% +/- 2.4% [mean +/- SE]) and spleen (SPL) (36.4% +/- 3.2%) in recipients of UCB cells was significantly higher (p < 0.001) than that observed in the BM (2.2% +/- 1.8%) and SPL (2.0% +/- 2.6%) in recipients of MPB. In subsequent studies, MPB was cultured for 2-8 days in cytokines prior to transduction to determine if longer prestimulation was required for optimal gene transfer. A significant increase in gene transfer into CD45(+) human cells and clonogenic cells derived from MPB SRCs was observed when cells were prestimulated for 6 days compared to 2 days prior to transduction (p = 0.019). However, even after 6 days of prestimulation, transduction was still significantly less than UCB. A substantial discrepancy exists in the ability to introduce genes effectively via retrovirus vectors into SRCs derived from MPB as compared to UCB.

Animals↗
PubMed2001

Loss of heterozygosity mapping at chromosome arm 16q in 712 breast tumors reveals factors that influence delineation of candidate regions.

Loss of heterozygosity (LOH) at the long arm of chromosome 16 occurs in at least half of all breast tumors and is considered to target one or more tumor suppressor genes. Despite extensive studies by us and by others, a clear consensus of the boundaries of the smallest region of overlap (SRO) could not be identified. To find more solid evidence for SROs, we tested a large series of 712 breast tumors for LOH at 16q using a dense map of polymorphic markers. Strict criteria for LOH and retention were applied, and results that did not meet these criteria were excluded from the analysis. We compared LOH results obtained from samples with different DNA isolation methods, ie., from microdissected tissue versus total tissue blocks. In the latter group, 16% of the cases were excluded because of noninterpretable LOH results. The selection of polymorphic markers is clearly influencing the LOH pattern because a chromosomal region seems more frequently involved in LOH when many markers from this region are used. The LOH detection method, i.e., radioactive versus fluorescence detection, has no marked effect on the results. Increasing the threshold window for retention of heterozygosity resulted in significantly more cases with complex LOH, i.e., several alternating regions of loss and retention, than seen in tumors with a small window for retention. Tumors with complex LOH do not provide evidence for clear-cut SROs that are repeatedly found in other samples. On disregarding these complex cases, we could identify three different SROs, two at band 16q24.3 and one at 16q22.1. In all three tumor series, we found cases with single LOH regions that designated the distal region at 16q24.3 and the region at 16q22.1. Comparing histological data on these tumors did not result in the identification of a particular subtype with LOH at 16q or a specific region involved in LOH. Only the rare mucinous tumors had no 16q LOH at all. Furthermore, a positive estrogen content is prevalent in tumors with 16q LOH, but not in tumors with LOH at 16q24.3 only.

Breast Neoplasms↗
PubMed2001

Accuracy of bedside clinical methods compared with fiberoptic endoscopic examination of swallowing (FEES) in determining the risk of aspiration in acute stroke patients.

This prospective study was undertaken to determine the accuracy of bedside clinical methods compared with fiberoptic endoscopic examination of swallowing (FEES) for detecting aspiration in acute stroke patients. Fifty patients underwent an examination of their ability to swallow 50 ml of water in 10-ml aliquots. Later their oxygen saturation levels before and after swallowing 10 ml of water were measured using a pulse oximeter. Oxygen desaturation of more than 2%, was considered to be clinically significant. All patients then underwent a FEES assessment by a speech therapist and were followed up during their inpatient stay for evidence of aspiration pneumonia. The oxygen desaturation test had a sensitivity of 76.9% and specificity of 83.3% (chi2 = 18.154, p = 0.00002), while the 50-ml water swallow test had a sensitivity of 84.6% and specificity of 75.0% (chi2 = 18.001, p = 0.00002). However, when these two tests were combined into one test called "bedside aspiration," the sensitivity rose to 100% with a specificity of 70.8% (chi2 = 27.9, p = 0.000001). Five (10%) patients developed pneumonia during their inpatient stay. The relative risk (RR) of developing pneumonia, if there was evidence of aspiration on FEES, was 1.24 (1.03 < RR < 1.49). We conclude that the oxygen desaturation test combined with the 50-ml water swallow test is suitable as a screening test to identify all acute stroke patients at risk of aspiration for further evaluation and management.

Acute Disease↗
PubMed2001

Increase in hepatic arterial blood flow after transjugular intrahepatic portosystemic shunt creation and its potential predictive value of postprocedural encephalopathy and mortality.

PURPOSE: To determine (i) whether there is a significant increase in hepatic artery blood flow (HABF) after transjugular intrahepatic portosystemic shunt (TIPS) creation and (ii) whether the extent of incremental increase in HABF is predictive of clinical outcome after TIPS creation. MATERIALS AND METHODS: Prospective, nonrandomized, nonblinded duplex Doppler ultrasound (US) examinations were performed on 24 consecutive patients (19 men; Child Class A/B/C: 4/12/8, respectively) with a mean age of 52.8 years who were referred for TIPS creation for variceal bleeding. Peak hepatic artery velocity and vessel dimensions were used to calculate the hepatic arterial blood flow (HABF) before and after TIPS creation. Patients were clinically followed in the gastrohepatology clinic and TIPS US surveillance was performed at 1 and 3 months to assess shunt function. The extent of incremental increase in HABF was analyzed as a predictor of post-TIPS encephalopathy and/or death. RESULTS: The technical success rate of TIPS creation was 100%. The shunt diameters were either 10 mm (n = 11) or 12 mm (n = 13). TIPS resulted in a significant reduction in the portosystemic gradient from 24.3 mm Hg +/- 5.7 to 9.3 mm Hg +/- 2.9 (P <.001). The hepatic artery peak systolic velocity and HABF increased significantly after TIPS creation, from 60.8 cm/sec +/- 26.7 to 121 cm/sec +/- 51.5 (P <.001) and from 254.2 mL/min +/- 142.2 to 507.8 mL/min +/- 261.3 (P <.001), respectively. The average incremental increase in HABF from pre-TIPS to post-TIPS was 253.6 mL/min +/- 174.2 and the average decremental decrease in portosystemic gradient was 15.0 mm Hg +/- 5.3, but there was no significant correlation (r = 0.04; P =.86) between the two. All shunts were patent at 30 and 90 days without sonographic evidence of shunt dysfunction. After TIPS creation, new or worsened encephalopathy developed in five patients at 30 days and in an additional three at 90 days. They were all successfully managed medically. Three patients (12.5%) died within 30 days of the TIPS procedure. The extent of incremental increase in HABF after TIPS was variable and did not correlate with the development of 30-day and 90-day encephalopathy (P =.41 and P =.83, respectively) or 30-day mortality (P =.2). CONCLUSIONS: HABF increases significantly after TIPS but is not predictive of clinical outcome. The significance of the incremental increase is yet to be determined.

Adult↗
PubMed2001

Accuracy of CO(2) angiography in vessel diameter assessment: a comparative study of CO(2) versus iodinated contrast material in a porcine model.

PURPOSE: To compare, with use of intravascular ultrasound (IVUS) as an internal reference standard in a porcine model, arterial diameters measured from arteriograms obtained with use of CO(2) to those obtained with use of iodinated contrast material (ICM). MATERIALS AND METHODS: In nine pigs, digital subtraction angiograms (DSAs) were obtained in the aorta and iliac arteries to compare vessel diameters measured with use of CO(2) to those measured with use of ICM. These measurements were divided by measurements made with use of intravascular ultrasound (IVUS) to yield a DSA/IVUS ratio. Differences between ICM and CO(2) were compared with analysis of variance to assess the effect of location (aorta vs iliac), contrast material used (ICM vs CO(2)), and position (posteroanterior, right anterior oblique, or left anterior oblique). Secondary analysis compared measurements of dependent and nondependent iliac arteries and compared the use of hand-injected CO(2) to that of CO(2) injected by an injector. RESULTS: The DSA/IVUS ratio was 70.7% +/- 4.4% with ICM use and 69.6% +/- 6.3% with CO(2) use, which did not represent a significant difference (P =.311). Animal position had no effect (P =.477). Underestimation was worse in the iliac arteries than in the aorta (67.4% +/- 1.5% vs 71.4% +/- 1.7%; P =.038). There was no difference in nondependent (P =.163) arteries, but CO(2) underestimated dependent iliac artery size more than ICM did (66.3% +/- 4.8% vs 70.3% +/- 5.4%; P =.051). Vessel diameter was underestimated more with the CO(2) injector than with hand-injected CO(2) (64.3% +/- 2.3% vs 71.7% +/- 1.7%; P <.0001). CONCLUSION: There is no difference in diameter underestimation between CO(2) and ICM in this animal model. Hand-injection of CO(2) causes less underestimation of vessel diameter than does the CO(2) injector.

Angiography↗
PubMed2001

Recent trends in central venous catheter placement: a comparison of interventional radiology with other specialties.

The authors determined changing trends and growth in tunneled and nontunneled central venous catheter placement procedures. With use of Medicare billing data for tunneled and nontunneled catheter placement, a comparison was made among interventional radiology (IR), surgery, anesthesia, and internal medicine. There has been substantial growth in the placement of central venous catheters. Currently, a minority of these procedures are performed in IR departments. However, there has been significant growth in the radiologic placement of both types of catheters.

Catheterization, Central Venous↗
PubMed2001

Prognostic value of TP53 gene mutation in adjuvant treated breast cancer patients.

We investigated the prognostic significance of mutation to the TP53 tumor suppressor gene in a series of 908 breast cancer patients treated with or without adjuvant therapies. The frequency of TP53 mutation detected by single strand conformation polymorphism (SSCP) was 19.4% (176/908) in the overall tumor series. In multivariate analysis, TP53 mutation was independently associated with worse survival in the overall (HR = 2.1, 95% CI [1.5-3.1], P<0.0001), non-adjuvant treated (HR=2.2, 95% CI [1.2-4.2], P=0.017) and adjuvant treated (HR= 2.0, 95% CI [1.3-3.1], P = 0.0009) patients.

Adult↗
PubMed2001

Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis.

OBJECTIVE: To investigate adult heights attained by patients with 21-hydroxylase deficiency and to perform a meta-analysis of height outcomes reported in this population. STUDY DESIGN: A retrospective chart review of our patients >5 years of age (n = 65) who were followed up from 1978 to 1998 for 21-hydroxylase deficiency was conducted. Final height (FH) SD scores and target height (TH) SD scores were determined. The impact of sex, time of diagnosis, and compliance was assessed. Meta-analysis of results from 18 studies was performed; TH was available for 204 of 561 patients. RESULTS: Mean FH SD score-TH SD score for our 65 patients was -1.03. For the meta-analysis, mean weighted FH SD score for all 561 patients was -1.37, whereas weighted mean FH SD score-TH SD score for the 204 patients for whom TH was available was -1.21. No difference in outcome was seen for males compared with females, although a statistically significant difference was seen for patients identified early versus late. CONCLUSIONS: Adult height in patients with 21-hydroxylase deficiency is often within 1 SD of TH. Early diagnosis and good compliance appear to improve the outcome. Rather than pursuing alternate therapies for congenital adrenal hyperplasia, efforts may instead be focused on early detection and improved compliance with traditional medical therapy.

Adrenal Hyperplasia, Congenital↗
PubMed2001

Characterization of a stress-induced alternate sigma factor, RpoS, of Coxiella burnetii and its expression during the development cycle.

Coxiella burnetii is an obligate intracellular bacterium that resides in an acidified phagolysosome and has a remarkable ability to persist in the extracellular environment. C. burnetii has evolved a developmental cycle that includes at least two morphologic forms, designated large cell variants (LCV) and small cell variants (SCV). Based on differential protein expression, distinct ultrastructures, and different metabolic activities, we speculated that LCV and SCV are similar to typical logarithmic- and stationary-phase growth stages. We hypothesized that the alternate sigma factor, RpoS, a global regulator of genes expressed under stationary-phase, starvation, and stress conditions in many bacteria, regulates differential expression in life cycle variants of C. burnetii. To test this hypothesis, we cloned and characterized the major sigma factor, encoded by an rpoD homologue, and the stress response sigma factor, encoded by an rpoS homologue. The rpoS gene was cloned by complementation of an Escherichia coli rpoS null mutant containing an RpoS-dependent lacZ fusion (osmY::lacZ). Expression of C. burnetii rpoS was regulated by growth phase in E. coli (induced upon entry into stationary phase). A glutathione S-transferase-RpoS fusion protein was used to develop polyclonal antiserum against C. burnetii RpoS. Western blot analysis detected abundant RpoS in LCV but not in SCV. These results suggest that LCV and SCV are not comparable to logarithmic and stationary phases of growth and may represent a novel adaptation for survival in both the phagolysosome and the extracellular environment.

Alternative Splicing↗
PubMed2001

Outcome of polyester cuff retention following traction removal of tunneled central venous catheters.

PURPOSE: To elucidate the factors that contribute to cuff retention during traction removal of tunneled catheters, as well as to determine the risk of complication associated with polyester cuff retention. MATERIALS AND METHODS: A total of 428 tunneled, cuffed catheters were removed with traction and local anesthesia. Polyester cuff retention was recorded when it occurred, and the effects of cuff retention were determined at a mean follow-up of 250 days. Statistical analysis was performed to determine the variables influencing cuff retention. RESULTS: Traction removal was successful in 428 (100%) patients. Of 428 catheters removed, 41 (10%) cuffs were retained. Silicone 10-F double-lumen and 9.6-F single-lumen catheters had a higher rate of cuff retention (27 [32%] of 84 and nine [39%] of 23, respectively) than did the split-tip polyurethane hemodialysis catheter (two [1%] of 196; P <.001). Cuff retention rates among other catheter types compared with that of the polyurethane catheter were not significantly different. Duration of catheter dwell did not significantly influence cuff retention. Of 41 retained cuffs, three required removal with cutdown for cuff migration to the exit site, which inhibited healing (n = 1); for suspected infection (n = 1); or for cosmetic purposes as requested by the patient (n = 1). The remaining patients had no complications associated with cuff retention. CONCLUSION: Traction removal of smaller-bore silicone catheters is more likely to result in cuff retention than removal of larger silicone and polyurethane catheters, and cuff retention is usually inconsequential.

Catheterization, Central Venous↗
PubMed2001

Hairy cell leukemia: treatment prospects.

The recent advances in the management of hairy cell leukemia, a chronic and indolent B-cell lymphoproliferative disorder are reviewed. The introduction of alpha-interferon, purine analogs and recombinant monoclonal antibodies/immunotoxins has dramatically improved the outcome in a disease that once had a dismal prognosis. The underlying genetic defect remains unknown.

Antibodies, Monoclonal↗
PubMed2001

The impact of swallowing disorders in the elderly.

INTRODUCTION: Swallowing disorders are common in the elderly but its prevalence is often underestimated. They can result in increased morbidity and mortality. METHODS: This article summarises the findings of selected published papers in major international journals indexed on Medline on swallowing using the key words--swallowing, dysphagia, aged, geriatrics and deglutition. RESULTS: There are age-related changes in the oral, pharyngeal and oesophageal functions. In the elderly, central nervous system diseases such as stroke, parkinsonism, dementia, medications, local oral and oesophageal factors are common causes of swallowing dysfunction. Swallowing disorders in the elderly are associated with increased mortality and morbidity. Aspiration, dehydration, pneumonia, malnutrition, functional decline and institutionalisation are often encountered in the elderly with dysphagia. There is a choice of different interventions available to reduce morbidity and mortality arising from swallowing impairments, and improving their quality of life. CONCLUSION: The effective management of swallowing impairment in the elderly requires a multidisciplinary team approach.

Age Factors↗