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Biomedical subjects

S Shenoy

Publications and source records attributed to S Shenoy.

At least 19 recordsLinked to original sources
PubMed2006

Altruistic living donors: evaluation for nondirected kidney or liver donation.

A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral. During the initial 30 months of program operations, 731 donor inquiries were received of which 131 individuals called back after review of mailed information materials. Forty-seven candidates initiated and 19 completed the evaluation process. Seven underwent donation to include six kidneys and one liver segment, five are actively pending donation, five were excluded from donation following transplant center evaluation and two took no further action after their intended liver recipients received deceased donor (DD) transplants. Psychological evaluation of these 19 candidates found them to be free of psychopathology, highly cooperative and self-directed. They did not exhibit attention-seeking or religious motivations for their actions. All seven donors and recipients continue to do well postoperatively. This evaluation program has made possible large-scale screening and education of prospective altruistic LD within the general population and also provides a unique opportunity to further our understanding of those individuals interested in living-nondirected donation.

Adult↗
PubMed2006

Incompatible kidney donor candidates' willingness to participate in donor-exchange and non-directed donation.

Although paired donation, list donation and non-directed donation allow more recipients to receive living donor transplants, policy makers do not know how willing incompatible potential donors are to participate. We surveyed 174 potential donors ruled out for ABO-incompatibility or positive cross-match about their participation willingness. They were more willing to participate in paired donation as compared to list donation where the recipient receives the next deceased donor kidney (63.8% vs. 37.9%, p < 0.001) or non-directed donation (63.8% vs. 12.1%, p < 0.001). Their list donation willingness was greater when their intended recipients moved to the top versus the top 20% of the waiting list (37.9% vs. 19.0%, p < 0.001). Multivariate logistic regression modeling revealed that potential donors' empathy, education level, relationship with their intended recipient and the length of time their intended recipient was on dialysis also affected willingness. For paired donation, close family members of their intended recipient (odds ratio (OR) = 3.01, confidence intervals (CI) = 1.29, 7.02), with high levels of empathy (OR = 2.68, CI = 1.16, 6.21) and less than a college education (OR = 2.67, CI = 1.08, 6.61) were more willing to participate compared to other donors. Extrapolating these levels of willingness nationally, a 1-11% increase in living donation rates yearly (84-711 more transplants) may be possible if donor-exchange programs were available nationwide.

Adult↗
PubMed2006

Improved islet yields from pancreas preserved in perflurocarbon is via inhibition of apoptosis mediated by mitochondrial pathway.

Islet transplantation is a treatment option for type I diabetic patients. Preservation of human pancreata prior to islet isolation using two-layer method with perfluorocarbon (PFC) and University of Wisconsin solution (UW) results in twofold increase in islet yields. The objective of this study was to determine the mechanism by which islets undergo apoptosis and determine PFC's effects on this process. Gene array analysis was used to analyze the expression of pro- and anti-apoptotic genes in islets isolated from pancreata preserved under varying conditions. A 12-fold increase in the expression of inhibitor of apoptosis (IAP) and survivin was observed in islets isolated from pancreata preserved in PFC. This was accompanied by decreased expression of BAD (3.7-fold), BAX (2.7-fold) and caspases (5.2-fold). Levels of activated caspase-9 (77.98%), caspase-2 (61.5%), caspase-3 (68.3%) and caspase-8 (37.2%) were also reduced. 'Rescue' of pancreata after storage (12 h) in UW by preservation using PFC also resulted in a down-regulation of pro-apoptotic genes and inhibition of caspase activation. Apoptosis observed in islets from all groups was mainly mitochondria-dependent, mediated by change in redox potential initiated by hypoxia. We demonstrate that reduction in hypoxia of pancreata preserved using PFC leads to significant up-regulation of anti-apoptotic and inhibition of pro-apoptotic genes.

Apoptosis↗
PubMed2005

A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders.

Bone marrow transplantation (BMT) benefits nonmalignant diseases but is limited by regimen-related toxicity, graft-versus-host disease (GVHD), donor availability, and graft rejection (GR). To overcome some of these barriers, we developed a new conditioning strategy for these patients. In total, 16 patients received Campath-1H (33/48 mg; days -21 to -19), fludarabine (150 mg/m(2); days -8 to -4), melphalan (140/70 mg/m(2); day -3), and transplant using related/unrelated stem cells. GVHD prophylaxis included cyclosporine/methylprednisolone for cord cells. Other recipients also received methotrexate. Risk factors for GR included multiple transfusions (6), low stem cell numbers (1), and immunologic/metabolic disorders (3). Donor engraftment was present in 14/16 recipients. Neutrophils (ANC>0.5 x 10(9)/l) and platelets (>50 x 10(9)/l) engrafted at a median of 13 and 24 days. Two patients died of Pseudomonas sepsis prior to engraftment, one of CMV disease, and another of intracranial hemorrhage. With median follow-up of 281 days (78-907), 12/16 are stable/improved, or cured. Acute GVHD was absent (n=10) or mild and transient (grade1-2 skin) (n=4). There was no chronic GVHD. Toxicities were predominantly early infections within 100 days, and correlated with lymphopenia (CD4+ T and B cells). Stable engraftment and low incidence of significant GVHD, irrespective of age or stem cell source, make this reduced-intensity regimen attractive for nonmalignant disorders.

Adolescent↗
PubMed2005

Efficacy and safety of rasburicase, a recombinant urate oxidase (Elitek), in the management of malignancy-associated hyperuricemia in pediatric and adult patients: final results of a multicenter compassionate use trial.

The recombinant urate oxidase, rasburicase (Elitek, Sanofi-Synthelabo, Inc.), has recently received regulatory approval for the prevention and treatment of hyperuricemia in children with leukemia, lymphoma, and solid tumors. Prior to approval, 682 children and 387 adults in the US and Canada received rasburicase on compassionate-use basis. Uric acid concentration declined rapidly in both adult and pediatric patients after rasburicase treatment. Similar responses were observed in patients treated with subsequent courses. Possible drug-related adverse events, including allergic reactions, were uncommon. These data confirm that rasburicase is effective and safe for the treatment and prophylaxis of children and adults with malignancy-associated hyperuricemia.

Adolescent↗
PubMed2003

Antitumor activity of 4-amino and 8-methyl-4-(3diethylamino propylamino)pyrimido[4',5':4,5]thieno (2,3-b) quinolines.

The interaction of 4-aminopyrimido [4',5':4,5] thieno (2,3-b) quinoline and 8-methyl-4-(3-diethylaminopropylamino) pyrimido [4',5':4,5] thieno (2,3-b) quinoline with DNA was studied by UV-Vis and fluorescence spectrophotometry as well as by hydrodynamic methods. On binding to DNA, the absorption spectra underwent bathochromic and hypochromic shifts and the fluorescence was quenched. These compounds are able to bind to DNA with an affinity of about 10(6) M(-1) for calf thymus DNA at ionic strength 0.01 M and their intercalating characteristic (lengthening of the DNA) depends upon the length of the chain. Binding to the GC-rich DNA of Micrococcus lysodeikticus was stronger than the binding to calf thymus DNA at ionic strength 0.01 M. The cytotoxicities of these compounds on leukemia HL-60, melanoma B16F10 and neuro 2a cells are quite similar and inhibition (IC50) is in the range of 0.992-3.968 microM. The anticancer efficacy against B16 melanoma, has provided evidence of major antitumor activity for 8-methyl-4-(3diethylaminopropylamino) pyrimido [4',5':4,5] thieno(2,3-b)quinoline. Single or multiple intraperitonial (i.p) doses of drug proved high level activity against the subcutaneous (s.c) grafted B16 melanoma, significantly increasing survival (p<0.001) and inhibiting tumor growth (T/C of 4%). This study offers a new intercalation functional group to DNA-targeted drug design.

Animals↗
PubMed2003

Hydroxychloroquine for the prevention of acute graft-versus-host disease after unrelated donor transplantation.

Hydroxychloroquine (HCQ) is an immunosuppressive agent that interferes with antigen presentation and with activity against graft-versus-host disease (GVHD). In a phase II trial assessing the GVHD prophylactic effects of HCQ, 51 consecutive unrelated donor transplant recipients received HCQ in addition to cyclosporin A, methylprednisolone, and methotrexate. HCQ was initiated on pretransplantation day -21 at 800 mg/d and continued until day +100 after transplantation. HCQ was extremely well tolerated and was not associated with side effects. Pharmacokinetic analyses demonstrated large inter- and intrapatient variability. The addition of HCQ did not affect posttransplantation immune recovery. Grade II to IV acute GVHD was observed in 56% of patients, and grade III and IV GVHD was observed in 17%. Day +100 mortality was 22%. When compared with a matched cohort of patients reported to the International Bone Marrow Transplant Registry, patients receiving HCQ had comparable cumulative incidences of grade II to IV acute GVHD. However, lower incidences of grades III and IV GVHD and better GVHD-free survival were observed in HCQ-treated patients (P =.01). We conclude that prophylactic HCQ is well tolerated and associated with a low incidence of severe acute GVHD. An ongoing placebo-controlled randomized trial will further determine what role HCQ plays in preventing GVHD after allografting.

Adolescent↗
PubMed2003

Birthweight-specific neonatal mortality in developing countries and obstetric practices.

OBJECTIVES: To evaluate birthweight-specific neonatal mortality and perinatal interventions in major medical centers in developed and developing countries. METHODS: A survey was developed and electronically mailed to 13 medical centers participating in the Global Network for Perinatal and Reproductive Health (GNPRH). The ability of a center to provide requested data was assessed. The mortality rates and use of specific perinatal interventions in centers in developing countries were compared with developed countries. RESULTS: Nine centers in developing countries responded to the survey, and three centers in developed countries were used for comparison. Data collection was highly variable. Most developing country centers were able to provide data by birthweight but not by gestational age. The differences in mortality rates between developing and developed countries were more pronounced at lower gestational ages and birthweights. A difference was found in perinatal interventions between developing and developed countries. In the former, viability was generally considered 28 weeks, and the gestational age at which cesarean sections were usually performed for the sake of the fetus at preterm gestations varied from 26 to 37 weeks. Most centers did not routinely induce for pPROM; only five out of nine centers used antibiotics to prolong latency. Most centers used tocolysis beginning at 26-28 weeks through 32-37 weeks, and a variety of tocolytic agents were used. Most centers routinely used corticosteroids for preterm infants, and all centers employed repeat weekly steroid dosing if undelivered. CONCLUSIONS: Despite the fact that the GNPRH centers included in this study represent some of the best health care available in these countries, they lag far behind centers in developed countries in neonatal mortality rates and their use of various obstetric practices. Furthermore, incomplete and inconsistent data collection complicates the evaluation of the factors contributing to high neonatal mortality rates.

Birth Weight↗
PubMed2002

Antibodies to 70 kD and 90 kD heat shock proteins are associated with graft-versus-host disease in peripheral blood stem cell transplant recipients.

The development of graft-versus-host disease (GVHD) can be modified by non-MHC factors. Based on our previous studies that showed an involvement of 70kD heat shock protein (hsp70) in the pathology of acute GVHD in a rat model, we determined serum levels of antibodies to hsp70, hsp90 and hsp60 in human recipients after allogeneic peripheral blood stem cell transplantation (PBSCT). Serum levels of these antibodies were correlated with GVHD status in the recipients. Twenty-nine recipients with high-risk haematological malignances, who received G-CSF mobilized allogeneic PBSCT from HLA matched family donors, were evaluated between 30 and 960 days after transplantation. Two recipients had no GVHD, 18 developed acute followed by chronic GVHD and nine developed only chronic GVHD. Patients with acute GVHD had a significant increase in IgM anti-hsp70 and/or anti-hsp90 early (30-90 days) after transplantation. In addition, an increase in IgM anti-hsp70 and/or anti-hsp90 antibodies preceded or accompanied chronic GVHD. Antibody levels returned to normal within the next 400 days in the majority of patients. Anti-hsp60 antibody levels were not different from control levels regardless of GVHD status. This study implies that the development of acute and/or chronic GVHD in humans is accompanied by an increase in anti-hsp70 and anti-hsp90 antibodies. Monitoring levels of anti-hsp70 and anti-hsp90 antibodies in stem cell transplant recipients may serve as a diagnostic tool and help to predict the onset of GVHD.

Adult↗
PubMed2002

Antibiotic sensitivity patterns of Pseudomonas aeruginosa strains isolated from various clinical specimens.

1567 clinical samples were obtained for the study; 494 strains of Pseudomonas aeruginosa were isolated (isolation rate of 31.52) and their antibiotic sensitivity patterns tested using Kirby Bauer disk diffusion method. The antibiotic sensitivity testing revealed that Pseudomonas aeruginosa strains were highly resistant to most anti-pseudomonal antibiotics; Amikacin was found to be most suitable for routine use with a sensitivity of 68.01% and the most resistant antibiotic was Netilmicin showing 70.04% resistance. Surprisingly, Gentamycin showed a relatively higher sensitivity of 55.87%. Sensitivity to Imipenem and Meropenem was 100%.

Anti-Bacterial Agents↗
PubMed2001

Defective apoptosis in lymphocytes and the role of IL-2 in autoimmune hematologic cytopenias.

Fas-mediated signaling is important for lymphocyte elimination. We investigated lymphocytes for Fas-signaling defects in 20 pediatric patients with chronic hematologic autoimmunity. In 5 of 20 (25%), there was profound resistance to exogenous FasL-mediated lysis, Fas mAb, and anti-CD3. FasL function, though variable, was not significantly different from that of simultaneously evaluated controls. Only 1 patient had a Fas mutation and manifestations of autoimmune lymphoproliferative syndrome. In contrast, lymphocytes from his clinically normal mother with the same mutation were normally sensitive to FasL. In 3 patients, normal Fas-mediated lysis was restored with rhIL-2. IL-2 had no effect in the other 2 patients. Activation and proliferation functions of IL-2 were normal in all 5. We conclude that altered Fas signaling, independent of Fas mutations, can precipitate hematologic autoimmunity. IL-2 can rescue some lymphocytes from this defect. In IL-2 refractory cases, a persistently defective response to IL-2 continues to confer a lymphocyte survival advantage. Hence, altered Fas pathway signaling with or without defective IL-2 responses should be considered in the etiology of hematologic autoimmunity.

Adolescent↗
PubMed2001

An international survey of practice variation in the use of antibiotic prophylaxis in cesarean section.

OBJECTIVE: To examine the use of antibiotic prophylaxis in cesarean section in different countries and in relation to a reference regimen. METHOD: Fifty consecutive cesarean sections performed in eight centers in five countries were surveyed. Data from each center were compared to a regimen recommended by the Cochrane Collaboration (one dose of ampicillin or cefazolin administered to all women shortly before the procedure or immediately after cord clamping) using logistic regression with adjustment for procedure type. RESULT: Prophylaxis was used widely, but only four centers administered prophylaxis to all women. Ampicillin and cefazolin were the principal antibiotics used, but broad-spectrum agents and multidrug regimens were also used commonly. Only two centers reliably administered the antibiotic at the appropriate time. The majority of women received only one dose of antibiotic in only three centers. CONCLUSION: The use of antibiotic prophylaxis in cesarean section was variable and often at odds with published recommendations.

Antibiotic Prophylaxis↗
PubMed2001

Renal transplantation following previous heart, liver, and lung transplantation: an 8-year single-center experience.

BACKGROUND: Long-term follow-up of heart, liver, and lung transplantation has led to an increased recognition of secondary end-stage renal failure (ESRF) in transplant recipients. This study examines our center's experience with renal transplantation following previous solid organ transplantation. METHODS: From January 1, 1992, to September 30, 1999, our center performed 18 renal transplants in previous solid organ recipients. During the same period, 815 total renal transplants were performed. One- and 3-year graft and patient survival, recipient demographics, donor type, and reason for transplantation were compared between these groups. RESULTS: Of the 18 recipients, 7 had prior heart transplants, 4 had prior liver transplants, and 7 had prior lung transplants. Cyclosporine toxicity contributed to renal failure in 17 (94.4%) of the patients-either as a sole factor (11 patients) or in combination with hypertension, renal artery stenosis, or tacrolimus toxicity (6 patients). Kaplan-Meier 1- and 3-year patient survival was 82.9% and 73.7%, compared with 95.5% and 90.7% in all renal transplant recipients. No surviving patient has suffered renal allograft loss. Mean current creatinine level is 1.4 mg/dL. CONCLUSIONS: Renal transplantation is an excellent therapy for ESRF following prior solid organ transplantation. One and 3-year patient and graft survival demonstrate the utility of renal transplantation in this patient population.

Follow-Up Studies↗
PubMed2001

Effect of prophylactic ondansetron on postoperative nausea and vomiting after elective craniotomy.

This prospective, randomized, placebo-controlled, double-blind study was designed to evaluate the efficacy of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting (PONV) after elective craniotomy in adult patients. The authors also tried to discover certain predictors for postcraniotomy nausea and vomiting. We studied 170 ASA physical status I and II patients, aged 15 to 70 years, undergoing elective craniotomy for resecting various intracranial tumors and vascular lesions. A standardized anesthesia technique and postoperative analgesia were used for all patients. Patients were divided into two groups and received either saline placebo (Group 1) or ondansetron 4 mg (Group 2) intravenously at the time of dural closure. Patients were extubated at the end of surgery and episodes of nausea and vomiting were noted for 24 hours postoperatively in the neurosurgical intensive care unit. Demographic data, duration of surgery, and anesthesia and analgesic requirements were comparable in both groups. Overall, a 24-hour incidence of postoperative emesis was significantly reduced in patients who received ondansetron compared with those who received a saline placebo (39% in Group 1 and 11% in Group 2, P = .001). There was a significant reduction in the frequency of emetic episodes and rescue antiemetic requirement in patients treated with ondansetron; however, ondansetron did not significantly reduce the incidence of nausea alone (14% in Group 2 vs 5% in Group 1, P = .065). Prophylactic ondansetron had a favorable influence on PONV outcome measures such as patient satisfaction and number needed to prevent emesis (3.5). Side effects were similar in both groups. We conclude that ondansetron 4 mg given at the time of dural closure is safe and effective in preventing emetic episodes after elective craniotomy in adult patients.

Adolescent↗
PubMed2001

Balloon angioplasty for arteriovenous graft stenosis.

PURPOSE: To retrospectively review the long-term outcome as well as the cost effectiveness of thrombolytic therapy and balloon angioplasty (TBA) versus surgical thrombectomy and balloon angioplasty (SBA) in the treatment of prosthetic dialysis access grafts. METHODS: Between February 1996 and February 1999, 63 hemodialysis patients (35 women; mean age 62.2 years) were treated for 105 thromboses in 6-mm polytetrafluoroethylene straight or loop bridge arteriovenous grafts. Choice of treatment was at the discretion of the surgeon or interventional radiologist: either Fogarty balloon thrombectomy followed by balloon dilation of the venous anastomotic stenosis or urokinase thrombolysis followed by angioplasty. RESULTS: Forty-eight SBAs and 55 TBAs were performed in 63 patients without complications. The primary patency rates in the entire cohort were 34%, 29%, and 17% at 1, 2, and 3 months, respectively. Primary patency after TBA was 29%, 18%, and 11%, and that for SBA, 45%, 45%, and 33% over the same time intervals. The mean graft survival was 10 days for TBA versus 31 days for SBA. Repeat angioplasty performed in 23 grafts produced secondary patency rates of 52% at 1 month, 34% at 3 months, and 5% at 5 months. The Medicare reimbursement for both treatments was identical ($1638 for TBA and $1670 for SBA). CONCLUSIONS: The poor patency rate and high cost of TBA and SBA suggests that these procedures should not be routinely used for salvage of thrombosed arteriovenous grafts with outflow stenosis. Patch angioplasty or creation of simultaneous temporary and new permanent accesses may be a more cost-effective approach in these patients.

Angioplasty, Balloon↗
PubMed2001

Stent-related iliac artery and iliac vein infections: two unreported presentations and review of the literature.

PURPOSE: To discuss the presentation, diagnosis, and treatment of stent-related infections on the basis of 2 new cases and historical review. CASE REPORTS: Two previously unreported cases of vascular stent infection are presented with a summary of cases from the literature. One case involved an iliac artery stent infection secondary to a remote bacteremia 6 months after stent placement. The other case was an early iliac vein stent infection, a previously unreported site of this complication. Both cases were diagnosed by use of computed tomography and were treated surgically after medical management failed. Both patients survived. CONCLUSIONS: A high index of suspicion is necessary for the diagnosis of stent infections, and an aggressive treatment is usually necessary for survival. Prophylactic antibiotics should definitely be considered in cases involving repeat interventions and prolonged catheterization, as well as before bacteremia-inducing therapies.

Aged↗