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Biomedical subjects

S Iyer

Publications and source records attributed to S Iyer.

At least 19 recordsLinked to original sources
PubMed2006

Reducing the risk of peripherally inserted central catheter line complications in the oncology setting.

At our institution, a retrospective review of peripherally inserted central catheters (PICCs) in oncology patients had previously demonstrated a complication rate of 40.7%. Since then we have implemented strategies to reduce complications including staff and patient education, insertion technique modification and PICC maintenance utilizing a PICC nurse. The objectives of this study were to evaluate the recent PICC complication rate and to compare it with the previously reported findings. Prospectively collected PICC complication data and medical records from all patients with solid tumours who had PICCs inserted in 2003 were analysed. A historical cohort comparative analysis was performed using our PICC complication rate from 2000 to 2001. Eighty-eight PICC lines were inserted in 73 patients under radiological guidance. The median PICC dwell time was 44 days (1-524 days). The overall complication rate was 15.9% (14/88) or 2.0 complications per 1,000 PICC-days. Infections developed in 5.7% (5/88) and thrombotic events occurred in 4.5% (4 /88) of PICCs. The mean time to complication was 45 days. The complication rate for 2003 was significantly lower than the rate for 2001 (P = 0.006), especially of infective complications (P = 0.004). Strategies introduced to reduce PICC complications may have been the reason for this improvement.

Adult↗
PubMed2006

Methicillin-resistant Staphylococcus aureus infection following arthroscopy of the knee joint.

Arthroscopic surgery of the knee is considered to be a safe procedure. We had a microbiologically confirmed infection of methicillin-resistant Staphylococcus aureus (MRSA). Although various rare infective cases are reported following arthroscopy of the knee joint, to the best of our knowledge there is no previous report of MRSA infection following arthroscopy of the knee joint.

Adult↗
PubMed2005

Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.

AIM: The aim of this study was to assess the incidence of liver failure in association with antidiabetic treatment using pioglitazone vs. other oral antidiabetic medications. METHODS: The study was a retrospective analysis of claim data from the PharMetrics Patient-Centric Database that had over 1.12 million enrollees with type 2 diabetes. All patients, > or =18 years of age with type 2 diabetes, who had initiated treatment either with a thiazolidinedione (pioglitazone and rosiglitazone), sulfonylurea or metformin were identified and matched on the basis of propensity scores, which served as a proxy for severity of disease. The primary measure of interest was the incidence of liver failure or hepatitis post-index date. In addition to unadjusted comparisons, Cox proportional hazard models were employed to estimate the risk of developing liver failure or hepatitis. RESULTS: There was no significant difference in the 1- and 2-year incidence rates of liver failure or hepatitis (primary and secondary diagnoses) between the pioglitazone monotherapy group and the respective comparator groups. In Cox proportional hazard models controlling for age, pre-index total healthcare costs, Charlson comorbidity index, procedures and a hospitalization or Emergency room (ER) visit for pre-index hyperglycaemia, and pioglitazone were not associated with an increased risk of liver failure or hepatitis, compared to all other defined groups. Furthermore, no primary or secondary diagnosis of liver failure was reported in the pioglitazone group during the follow-up period. CONCLUSIONS: Results of retrospective data analysis demonstrate no evidence of increased risk of liver failure or hepatitis for patients initiating therapy on pioglitazone, compared to other oral antidiabetic agents. Pioglitazone therapy was not associated with an increased risk of liver failure at 2 years relative to other oral antidiabetic therapies.

Administration, Oral↗
PubMed2004

The risk of child and adolescent mortality among vulnerable populations in Rio de Janeiro, Brazil.

This study investigated the importance of socioeconomic factors such as education, income, religion, family structure and residence in explaining the increased risk of mortality among vulnerable populations aged less than 20 years in Rio de Janeiro, Brazil. Data used were from the 1991 Brazilian Demographic Census and comprised 121,060 women aged 15-49 residing in Rio de Janeiro. Two alternative statistical methods were used to calculate the risk of death: the widely used Brass method (an indirect estimate which assesses population risks) and a case-control study (which assesses individual risks). The study also focused on the importance of indicators of human and social capital, the lack of which may explain the higher risk of death among children and adolescents. Lack of education was found to be a major determinant of mortality at young ages. Residence in a favela (shantytown), families in which mothers were the head of the family, and a lower median level of income were found to be significant determinants of mortality among vulnerable populations in Brazil. However, religion was not found to be as important a predictor of high mortality.

Adolescent↗
PubMed2004

Induction of long-term cardiac allograft survival by heme oxygenase-1 gene transfer.

Elevated expression of heme oxygenase-1 (HO-1), an intracellular enzyme that degrades heme into carbon monoxide (CO), biliverdine and free iron, has anti-inflammatory and antiapoptotic effects in diverse models. Here, we analyzed the effects of specific overexpression of HO-1 following adenovirus-mediated (AdHO-1) gene transfer in an acute cardiac allograft rejection model. The intragraft (i.g.) injection of AdHO-1 into cardiac allografts, as well as intramuscular (i.m.) or intravenous (i.v.) administration, prolonged allograft survival with, respectively, 13.3, 62.5 and 80% of the grafts surviving long term (>100 days), whereas control grafts were rejected with acute kinetics. HO-1 overexpression was associated with inhibited allogeneic responses in MLRs using graft-infiltrating leukocytes and splenocytes, but not with lymph node cells. The inhibition of splenocyte proliferation was mediated by soluble factors and was dependent on the presence of APCs, since purified T cells proliferated normally. i.v. but not i.g. AdHO-1 administration decreased the number of graft-infiltrating leukocytes, cytokine mRNA accumulation and apoptosis in transplanted hearts, whereas i.v. and i.g. AdHO-1 did not modify normal immune responses against cognate antigens, indicating that there was no general immunosuppression. These results indicate that HO-1 overexpression prolongs the survival of vascularized allografts by promoting tolerogenic mechanisms acting on allogeneic cellular immune responses.

Adenoviridae↗
PubMed2004

Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature.

BACKGROUND: Wolcott-Rallison syndrome is a rare autosomal recessive condition characterized by early infancy onset diabetes mellitus and multiple epiphyseal dysplasia. So far, 17 children have been described in the world literature. Recently, mutations in the gene encoding EIF2AK3 have been shown to segregate with the syndrome in three affected families. AIMS: We aimed to describe the clinical characterization and mutation analysis of a further child, and full clinical and follow-up details on our first family including the longest surviving child. METHODS: Retrospective case notes review of three children presenting to the diabetic unit at our institution; mutation analysis of the EIF2AK3 gene in our most recent patient; and review of the literature on Wolcott-Rallison syndrome. RESULTS: Previously unreported phenotypic features in our patients included developmental regression after episodes of hepatic failure, and pachygyria on brain imaging. We have identified a novel 4-base pair deletion (nt 3021-3024 del GAGA) in exon 13, which results in a frameshift and premature stop codon (R908 F/S +22X), causing premature truncation of the protein and abolition of the carboxy-segment of the catalytic domain. CONCLUSIONS: Wolcott-Rallison syndrome causes early-onset diabetes and acute hepatic failure, before epiphyseal dysplasia is manifest. We have identified a novel mutation in EIF2AK3, and prenatal diagnosis may now be offered to affected families.

Adolescent↗
PubMed2003

Generation of heme oxygenase-1-transgenic rats.

Heme oxygenase-1 (HO-1) expression protects cells from a variety of cellular insults and inhibits inflammation. However, its role in the regulation of immune responses has not yet been clearly established. We generated HO-1 transgenic rats to directly test the impact of HO-1 on the different immune mechanisms. To temporally control the expression of HO-1, we used a one-plasmid tetracycline (tet)-inducible system. This plasmid contains the H-2K(b) promoter, which transcribes the tet transactivator (tTA) and expression of a human HO-1 cDNA is obtained in the absence of tetracycline. The DNA construct was microinjected into one-cell rat embryos and mothers and pups were maintained with tetracycline. Eight transgenic founders were obtained. Analysis of transgene expression in the absence of tet showed that 2 lines (12.4 and 12.6) expressed HO-1 mRNA in several organs (as detected by reverse transcription polymerase chain reaction) and at the protein level only in the thymus. Expression levels of transgene-derived HO-1 increased after withdrawal of tet compared with transgenic rats maintained with tet, as detected by analysis of mRNA levels by quantitative real-time reverse transcription polymerase chain reaction. Gross examination and histopathological analysis of several organs in both lines showed no anomalies. Thymocytes and splenocytes of both lines showed normal cell subpopulations and allogeneic proliferation compared with controls. Systemic immune responses against cognate antigens were normal in both lines, as evaluated by the proliferation of lymph node cells and the production of antibodies against keyhole limpet hemocyanin after immunization. Animals from line 12.6 rejected transplanted allogeneic hearts with the same kinetics as controls. In conclusion, short-term induction of HO-1 overexpression did not modify immune responses compared to those of control non-transgenic animals.

Animals↗
PubMed2002

Inhibition of graft arteriosclerosis development in rat aortas following heme oxygenase-1 gene transfer.

Heme oxygenase 1 (HO-1) is an enzyme which degrades heme into tree end products: biliverdin, free iron and carbon monoxide. This enzyme has recently been shown to have anti-inflammatory and tissue protective effects. HO-1 expression is involved in organ protection in pathological situations, and immunosuppressive treatments resulting in indefinite graft survival without chronic rejection have been associated with HO-1 expression by cells of the vessel wall. The aim of this study was to analyze the effect of specific HO-1 overexpression. We used a recombinant adenovirus coding for human HO-1 cDNA in a rat aorta chronic rejection model, 30 days after transplantation. Control groups included rats non treated or treated with a non-coding adenovirus Addl324. We first demonstrated that AdHO-1 was efficiently expressed in endothelial cells in vitro, and in rat aortas ex vivo after adenovirus gene transfer. We found that intimal thickening in AdHO-1 treated aortas (10.8 +/- 3.8%, n=5) was significantly decreased compared to untreated (21.2 +/- 5.6%, n = 5) or Addl324-treated (21.1 +/- 1.2%, n = 4) aortas. Immunohistology showed that treatment with AdHO-1 resulted in a significant reduction in leukocyte infiltration and a decreasing number of VSMC in the intima, compared to Addl324-treated aortas. However, this effect of HO-1 on chronic rejection did not imply modifications on numbers of apoptotic cells in the graft or of alloantibody levels. We have demonstrated, for the first time, that specific HO-1 overexpression following gene transfer of HO-1 inhibited chronic rejection by reducing leukocyte and VSMC infiltration of the aorta intima.

Adenoviridae↗
PubMed2002

H. pylori infection and genotyping in patients undergoing upper endoscopy at inner city hospitals.

Kings County Hospital (KCH), and St. John's Episcopal Hospital (SJH) are inner-city hospitals in New York City serving predominantly minority populations. Staten Island University Hospital (SIUH) serves a predominantly middle-class Caucasian population. We examined H. pylori (HP) infection in patients undergoing upper endoscopy at these hospitals. Two gastric biopsies were obtained from each patient. One biopsy was examined by histology or the rapid urease test for the presence of HP. The other was subjected to analysis by PCR to detect HP DNA and to identify putative HP virulence factors. Of 200 subjects, 54% were African-American, 10% were Hispanic, and 36% were Caucasian. HP infection rates in African-American, Hispanic, and Caucasian patients were 43%, 20%, and 11%, respectively. Many of the African-American patients are recent immigrants from the Caribbean Islands. In these patients, an inverse relationship was observed between HP infection and the number of years living in the United States. Higher levels of HP infection were observed in patients with duodenitis and peptic ulcer disease. With respect to HP virulence factors, the vacA s1b and m1 alleles, as well as the iceA2 allele were the predominant alleles expressed in HP-positive samples obtained from African-Americans. The cagA gene was detected in 81% of HP-positive samples. However, CagA positivity was not related to any specific gastrointestinal disorder. Our findings indicate that among several ethnic groups served by three hospitals, African-American patients have the highest rate of HP infection. Moreover, in AfricanAmerican patients undergoing endoscopy: (1) HP infection was inversely related to the number of years the patients have been living in the USA; (2) HP infection rates were higher in patients diagnosed with duodenitis and peptic ulcer disease versus other disorders; (3) expression of the CagA gene was not associated with any specific gastroduodenal disorder; and (4) there was little allelic heterogeneity with respect to VacA and IceA subtypes. These findings suggest that inner-city African-Americans are more likely to be infected with HP and suffer from more serious gastroduodenal disorders than other ethnic groups.

Black or African American↗
PubMed2002

Etanercept for severe psoriasis and psoriatic arthritis: observations on combination therapy.

BACKGROUND: The antitumour necrosis factor (TNF) activity of etanercept has been utilized to generate an important and novel treatment for rheumatoid arthritis. TNF has also been implicated in the pathogenesis of psoriasis. OBJECTIVES: To determine whether blockade of TNF activity by etanercept may provide an additional treatment option for patients with psoriasis. METHODS: In an uncontrolled trial, etanercept was added to the treatment regimen in six patients with severe recalcitrant psoriasis (three also with psoriatic arthritis) partially resistant to other ongoing systemic agents. RESULTS: In each case, the disease activity showed marked improvement on addition of etanercept therapy. No added toxicity was found with etanercept. CONCLUSIONS: Etanercept appears to be a promising immunomodulatory agent that can be used in combination therapy for the treatment of psoriasis, and a prospective controlled trial may be warranted.

Adult↗
PubMed2001

Effect of short pulsed nonablative infrared laser irradiation on vascular cells in vitro and neointimal hyperplasia in a rabbit balloon injury model.

BACKGROUND: Neointimal hyperplasia after PTCA is an important component of restenosis. METHODS AND RESULTS: Cultures of rabbit endothelial cells and smooth muscle cells (SMCs) were irradiated with different doses of nonablative infrared (1064-nm) radiation. Normalized viability index detected with nondestructive Alamar Blue assay and direct cell count were studied. Our experiments demonstrated dose-dependent cytostatic or cytotoxic effects of laser irradiation. We also evaluated the long-term effect of endoluminal nonablative infrared laser irradiation on neointimal hyperplasia in a rabbit balloon injury model. PTCA of both iliac arteries of 23 New Zealand White rabbits was performed. One iliac artery was subjected to intra-arterial subablative infrared irradiation via a diffuse tip fiber. The contralateral vessel served as control. The diet was supplemented with 0.25% cholesterol and 2% peanut oil for 10 days before and 60 days after PTCA. Morphometry after 60 days showed that intimal areas were 0.76+/-0.18 and 1.85+/-0.30 mm(2) in the laser and control arteries, respectively (P=2.2x10(-11)). CONCLUSIONS: We conclude that nonablative infrared laser inhibited neointimal hyperplasia after PTCA in cholesterol-fed rabbits for up to 60 days.

Angioplasty, Balloon, Coronary↗
PubMed2001

Mechanisms of JP-8 jet fuel toxicity. I. Induction of apoptosis in rat lung epithelial cells.

JP-8 is a kerosene-based fuel widely used by the U.S. military. Various models of human occupational and animal exposure to JP-8 have demonstrated the potential for local and systemic toxicity but the mechanisms involved are unknown. The purpose of our investigation was to study the molecular mechanisms of JP-8 toxicity by using an in vitro model. JP-8 exposure in a rat lung alveolar type II epithelial cell line (RLE-6TN) induces biochemical and morphological markers of apoptotic cell death: caspase-3 activation, poly(ADP-ribose) polymerase (PARP) cleavage, chromatin condensation, membrane blebbing, cytochrome c release from mitochondria, and genomic DNA cleavage into both oligonucleosomal (DNA ladder) and high-molecular-weight (HMW) fragments. The human histiocytic lymphoma cell line (U937) also responds to JP-8 with caspase-3 activation, cleavage of caspase substrates, including PARP, DNA-PK, and lamin B1, and degradation of genomic DNA with the production of HMW fragments. Caspase-3 activation and PARP cleavage also occur in the acute T-cell leukemia cell line (Jurkat) following treatment with JP-8. Furthermore, Jurkat cells stably transfected with a plasmid encoding the antiapoptotic protein Bcl-x(L) or pretreated with the pan-caspase inhibitor Boc-d-fmk, are relatively resistant to the cytotoxic effects of JP-8 compared to control cells. Finally, we demonstrate that PARP cleavage occurs in primary mouse thymocytes exposed to JP-8. In conclusion, our data support the hypothesis that apoptotic cell death is responsible at least partially for the cytotoxic effects of JP-8 and suggest that inhibition of the apoptotic cascade might reduce JP-8 toxicity.

Animals↗
PubMed2001

Short telomeres in yeast are highly recombinogenic.

We report that recombination rates specifically increase by up to 10(3) near shortened telomeres in K. lactis cells. This occurs in cells lacking telomerase that undergo growth senescence as well as in cells with stably shortened telomeres that cause little effect on cell growth. The high rates of gene conversion allowed a subtelomeric marker, initially present at a single telomere, to efficiently spread to most or all other telomeres in the cell. We propose that short telomeres in K. lactis are not fully competent at capping chromosome ends and hence are occasionally processed by proteins that normally act to repair broken DNA ends through recombination. This helps explain how recombination can be frequent enough to permit maintenance of telomeres in yeast cells lacking telomerase.

DNA Repair↗
PubMed2001

A double-blind, side-by-side comparison study of low fluence long pulse dye laser to coolant treatment for wrinkling of the cheeks.

BACKGROUND: Nonablative laser resurfacing with various lasers and light sources can improve skin texture and fine lines. The 595 nm pulsed dye laser has been reported to improve rhytides through nonablative mechanisms, minimizing the side effects and recovery period associated with traditional ablative resurfacing techniques. OBJECTIVE: The purpose of this study was to investigate the efficacy of the long pulse flashlamp pumped pulsed dye laser (LPDL) in improving rhytides and stimulating collagen synthesis and dermal remodeling. METHODS: The cheeks of 15 women with moderate to severe photoaging were treated on one side with a series of four monthly LPDL treatments, while the contralateral cheek was treated with cryogen coolant only. Clinical grading was performed at monthly intervals for up to 3 months after the fourth LPDL treatment. Skin biopsy before treatment and at 4-6 weeks was also performed for histologic evaluation and staining for type I procollagen. RESULTS: Eleven of 15 patients demonstrated improvement of the laser-treated cheek while only three of 15 patients the demonstrated improvement on the cryogen-treated cheek. A statistically significant (p = 0.0035) improvement in clinical grading of photodamage was noted in the treated side versus the control. In those patients who improved with LPDL treatment, an improvement of 18.1% in the mean pre- and post-treatment clinical grading scores was observed. Histologic evaluation demonstrated an increase in activated fibroblasts with positive procollagen staining on the LPDL-treated cheek. CONCLUSION: The 595 nm LPDL may be used in the treatment of moderate to severe wrinkles. A mild improvement may be expected with minimal to no side effects.

Adult↗
PubMed2001

Embolization via collateral circulation during carotid stenting with the distal balloon protection system.

PURPOSE: To describe a potential route for embolization to the middle cerebral artery (MCA) during carotid stenting with the distal balloon protection system. CASE REPORT: An 82-year-old man with symptomatic severe carotid artery stenosis underwent elective carotid stenting with distal-balloon protection. Despite complete occlusion of the distal internal carotid artery, frequent emboli were detected in the ipsilateral MCA by transcranial Doppler (TCD) during the procedure. Intracranial angiography, performed during the distal-balloon protection, revealed filling of the MCA through collaterals from the ipsilateral external carotid artery. The procedure was successfully completed without complications. The patient remains asymptomatic at 6 months. CONCLUSIONS: During carotid stenting with distal-balloon protection, asymptomatic embolization into the ipsilateral MCA may occur through collateral circulation. The clinical significance of these emboli is uncertain.

Aged↗
PubMed2001

Inhibition of cutaneous UV light-induced tumor necrosis factor-alpha protein production by Allotrap 1258, a novel immunomodulatory peptide.

Peptides derived from the heavy chain of the HLA Class-I molecules have been shown to modulate immune responses both in vivo and in vitro. Using a computer-aided rational drug design approach, novel immunomodulatory peptides were designed based on peptide 2702.75-85, derived from HLA-B2702. Several peptides were identified which had increased immunomodulatory activity, including peptides RDP1258 and its D-isomer the peptide Allotrap 1258. The present study using Skh/hr hairless mouse skin model evaluated the in vivo effects of Allotrap 1258 on acute UVB-induced skin inflammation. Here we demonstrate that intraperitoneal administration of Allotrap 1258 1 h prior to UV exposure resulted in significantly diminished levels of UV-induced tumor necrosis factor (TNF)-alpha protein production in the epidermis but had no effect on other parameters of the acute UV-induced inflammatory response. By virtue of its ability to suppress TNF-alpha protein production, Allotrap 1258 could prove to be an effective modulator of inflammatory responses.

Adjuvants, Immunologic↗