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Biomedical subjects

S Reddy

Publications and source records attributed to S Reddy.

At least 73 records · Page 4Linked to original sources
PubMed2000

Anterior ischemic optic neuropathy: a complication after systemic inflammatory response syndrome.

BACKGROUND: Patients are surviving previously fatal injuries. Unique morbidities are occurring in these survivors. Anterior ischemic optic neuropathy represents a previously unrecognized cause of blindness in the trauma victim. We hypothesize that this phenomenon is caused by unique characteristics of optic edema/ pressure or decreased blood flow associated with massive resuscitation. METHODS: Between November of 1991 and August of 1998, there were 18,199 admissions to our trauma center. Of this group, 350 patients required massive volume resuscitation (>20 liters infused over first 24 hours). Patients having closed head injuries, facial fractures or direct orbital trauma were excluded from study. The following variables were studied: demographics, injury severity (Injury Severity Score, highest lactate, worst base deficit, and lowest pH) crystalloid and transfusion requirements, ventilator requirements (PEEP) RESULTS: Of the 350 patients with massive resuscitation, 9 patients were diagnosed with anterior ischemic optic neuropathy (2.6%). Of these, seven patients required celiotomy (78%). Six of the seven celiotomy patients had damage control celiotomies and abdominal compartment syndrome (86%). One patient had a repair of a subclavian artery; one had a complex acetabular repair. Blindness was unilateral in five patients and bilateral in four. All nine patients had evidence of global hypoperfusion, systemic inflammatory response, massive resuscitation, and high ventilatory support; one patient required cardiopulmonary resuscitation. CONCLUSION: Prone positioning is known to be associated with an increased intraocular pressure. We postulate that the combination of massive resuscitation and prone positioning will increase the incidence of anterior ischemic optic neuropathy. As such, we recommend that prone positioning for adult respiratory distress syndrome be reserved for only those patients at risk of death.

Adolescent↗
PubMed2000

Prevention of autoimmune diabetes by oral administration of syngeneic pancreatic extract to young NOD mice.

Oral administration of relevant autoantigens is being considered as a realistic approach for the prevention of several autoimmune diseases. In this study we administered, orally, to young female NOD/Ak mice (diabetes incidence, 40%) and NOD/LtJ mice (diabetes incidence, 70%) whole pancreatic extract on days 19, 20, 21, 22, 23, 26, and 27 and studied its effects on the development of diabetes until day 250. The cumulative incidence of diabetes in both the colonies after pancreatic extract treatment was compared with the incidence after oral administration of syngeneic liver extract or in untreated mice. In the NOD/Ak mice, the incidence of diabetes in the pancreatic extract group was significantly lower (6%; n = 34, p = 0.004) and was delayed compared with 33% in the liver group (n = 34) and 44% in the untreated group (n = 18). Significant protection from diabetes and a delay in its onset also were observed in the NOD/LtJ mice treated with pancreatic extract (16%; n = 19, p = 0.002) compared with those liver extract treated (72%; n = 18) and in untreated mice (60%; n = 22). Pancreatic histology at day 90 from all the study groups showed that the protection from diabetes in the pancreatic-extract group was not associated with reduced insulitis. We speculate that the marked disease protection observed in this study with orally administered pancreatic extract may be associated with the presence of immunoregulatory cells with a predominant Th2 cytokine bias. Our studies may have implications for the prevention of insulin-dependent diabetes mellitus (IDDM) in humans.

Administration, Oral↗
PubMed2000

Diagnosis of invasive amebiasis by enzyme-linked immunosorbent assay of saliva to detect amebic lectin antigen and anti-lectin immunoglobulin G antibodies.

Saliva from subjects with amebic liver abscess (ALA), acute amebic colitis, asymptomatic infection with Entamoeba histolytica or Entamoeba dispar, and uninfected controls was tested by enzyme-linked immunosorbent assay (ELISA) for the presence of E. histolytica galactose-inhibitable lectin antigen and salivary immunoglobulin (IgG) antibodies to a recombinant cysteine-rich lectin-derived protein (LC3). Salivary lectin antigen was found in 65.8% of subjects with acute colitis, compared to 22.2% of those convalescent from ALA, 10.0% with asymptomatic E. histolytica infection, 9.8% with E. dispar infection, and 2.6% of controls (subjects from the United States and study patients with nonamebic diarrhea) (P < 0.001 for each compared to values for subjects with colitis). Salivary anti-LC3 IgG antibodies were found in 92% of ALA patients regardless of duration of illness and in 83.3% of colitis patients who were symptomatic for at least 7 days (P < 0.001 compared to other study groups). Serum anti-LC3 IgG antibodies were detected in 56.3% of subjects with acute colitis, 100% of subjects with ALA or prolonged colitis, 45% of subjects with asymptomatic E. histolytica infection, 32.3% of subjects with E. dispar infection, and 23.4% of diarrhea controls. In comparison to ELISA for serum anti-LC3 IgG antibodies, the salivary lectin antigen assay is a more sensitive and specific test for acute amebic colitis. Detection of salivary anti-LC3 IgG antibodies by ELISA is an effective means for the diagnosis of ALA and prolonged cases of amebic colitis.

Antibodies, Protozoan↗
PubMed2000

Expression and regulation of a molecular marker, SPR1, in multistep bronchial carcinogenesis.

A small proline-rich protein, SPR1, is overexpressed in squamous metaplasia of bronchial epithelium. We studied the expression and regulation of SPR1 in a series of human bronchial epithelial cell lines representing a model of multistep bronchial carcinogenesis. These cell lines included a primary culture of tracheobronchial epithelial cells (HTBE), a papilloma virus-transformed tracheobronchial epithelial cell line (HBE1), a cell line selected from HBE1 by a tobacco carcinogen and a phorbol ester (HBE1-C), a simian virus-transformed bronchial epithelial cell line (BEAS-2B), and a lung carcinoma cell line (H460). Different tumorigenic potentials of these cell lines were indicated by graded levels of telomerase activity. Concomitant with squamous transformation, there was an increase in SPR1 expression in HTBE, HBE1, and HBE1-C that was reversible by vitamin A. With progression of tumorigenicity, there was a marked reduction in SPR1 expression in BEAS-2B and a total loss of expression in H460. In these latter cell lines representing advanced malignant transformation, there was a loss of up- and downregulation, respectively, by the phorbol ester and vitamin A. Transfection study with chimeric constructs of the SPR1 promoter and a reporter gene showed that the dysregulation of SPR1 expression in malignant transformation was a result of perturbation of the basal and enhancer elements of the first 162 nucleotides in the 5'-flanking promoter region of the SPR1 gene. These findings suggest an association of transcriptional dysregulation of the SPR1 gene with multistep bronchial carcinogenesis.

Animals↗
PubMed2000

Genetic susceptibility to ozone-induced lung hyperpermeability: role of toll-like receptor 4.

The pollutant ozone (O(3)) induces lung hyperpermeability and inflammation in humans and animal models. Among inbred strains of mice, there is a 3-fold difference in total protein (a marker of permeability) recovered in bronchoalveolar lavage (BAL) fluid after a 72-h exposure to 0.3 ppm O(3). To determine the chromosomal locations of susceptibility genes, we performed a genome screen using recombinant inbred (RI) strains of mice derived from O(3)-susceptible C57BL/6J (B6) and O(3)-resistant C3H/HeJ (HeJ) progenitors. Each RI strain was phenotyped for O(3)-induced hyperpermeability, and linkage was assessed for 558 markers using Map Manager QTb27. A significant quantitative trait locus (QTL) was identified on chromosome 4. The likelihood ratio chi(2) statistic (16.6) for the peak of the QTL was greater than the significance threshold (16.3) determined empirically by permutation test. This QTL contains a candidate gene, Toll-like receptor 4 (Tlr4 ), that recently has been implicated in innate immunity and endotoxin susceptibility. The amount of the total trait variance explained by the QTL at Tlr4, the gene with the highest likelihood ratio statistic in the QTL, was approximately 70%. To test the role of Tlr4 in O(3)-induced hyperpermeability, BAL protein responses to O(3) were compared in C3H/HeOuJ (OuJ) and HeJ mice that differ only at a polymorphism in the coding region of Tlr4. Significantly greater protein concentrations (430 +/- 35 microg/ml) were found in OuJ mice compared with HeJ mice (258 +/- 18 microg/ml) after exposure to O(3). Furthermore, reverse transcriptase/polymerase chain reaction analysis demonstrated differential expression of Tlr4 message levels between HeJ and OuJ mice after O(3) exposure. Together, results indicate that a QTL on mouse chromosome 4 explains a significant portion of the genetic variance in O(3)-induced hyperpermeability, and support a role for Tlr4 as a strong candidate susceptibility gene.

Air Pollution↗
PubMed2000

Is there a difference between right and left femoral bone density?

Because of the known differences in bone mineral density (BMD) of the dominant and nondominant forearms, it has been customary to measure BMD of the nondominant forearm to reduce variance. However, it is less clear whether such systematic differences exist between BMD of the two hips. Accordingly, we measured BMD of both hips and the spine in 131 consecutive white women who presented to a community based private practitioner for evaluation and advice on osteoporosis. There was a highly significant correlation between BMD of the two hips at the femoral neck, trochanter, and Ward's triangle (r = 0.91, 0.93, and 0.89; p < 0.0001 for all three sites), and also between BMD at various measurement sites in the hip and the spine BMD (p < 0.0001). Although, there was no significant difference between the right and left femoral neck BMD, there were small (approximately 1-2.5%) but significant differences between BMD of the two hips at the trochanter and Ward's triangle (p = 0.008 and 0. 005, respectively). The left hip BMD was consistently higher than the right hip BMD at all measurement sites. Because of the small sample size of the left-handed persons, we were unable to determine the influence of dominant handedness on hip BMD. We concluded the following: (1) BMDs of the two hips are highly correlated at relevant measurement sites; (2) there does not appear to be a dominant hip as there is dominant forearm; (3) because of strong agreement between BMD of the two hips there is little justification to measure both hips in routine clinical practice.

Adult↗
PubMed2000

Dual-label immunohistochemical study of interleukin-4-and interferon-gamma-expressing cells within the pancreas of the NOD mouse during disease acceleration with cyclophosphamide.

Beta cell destruction has been shown to occur when rodent or human islets are exposed in vitro to inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). Other cytokines such as interleukin-4 (IL-4) or interleukin-10 (IL-10), when given to NOD mice, prevent insulin-dependent diabetes mellitus (IDDM). In this study, we have employed immunofluorescence histochemistry to study the expression of IFN-gamma and IL-4 in the pancreas of female NOD mice at various time-points (days 0, 4, 7, 11 and at onset of diabetes) following disease acceleration with cyclophosphamide (Cy). Dual-label confocal and light microscopy were employed to determine the precise cellular sources of the two cytokines. IL-4 immunolabelling was observed in a few immune cells at days 0, 4, and 7 within the pancreatic islets but in larger numbers at day 11 and at onset of diabetes. The cytokine was co-localized predominantly in CD4 cells, while only a small minority of CD8 cells and macrophages also expressed IL-4. At days 0, 4, 7 and 11, weak to moderate immunolabelling for IL-4 was also observed in beta cells. In contrast, immunolabelling for IFN-gamma within the islets was not observed until day 11 and this labelling persisted at onset of diabetes. It was immunolocalized in macrophages and to a lesser extent in CD4 cells. Only a few CD8 cells were immunopositive for IFN-gamma. At day 11, a proportion of beta cells showed weak immunolabelling for IFN-gamma. During the study period, immunolabelling for IFN-gamma was also observed in a proportion of endothelial cells located in the intra-islet and exocrine regions of Cy and diluent-treated mice. From day 11 onwards, both the cytokines were observed in some of the peri-vascular regions. Our results demonstrate that during Cy-induced diabetes, there is increasing expression of both IL-4 and IFN-gamma in specific immune cells within the inflamed islets in the late prediabetic stage and at onset of diabetes. Further studies are required to correlate our protein immunohistochemical findings with in situ cytokine gene expression and to determine whether there is a clear Th1 cytokine protein bias at clinical onset of diabetes and immediately preceding it.

Animals↗
PubMed2000

Active, multisite, laboratory-based surveillance for Cryptosporidium parvum.

Cryptosporidium parvum leaped to the attention of the United States following the 1993 outbreak in Milwaukee, Wisconsin, which sickened 400,000 people. Other outbreaks in the United States have been associated with drinking and recreational water, consumption of contaminated foods, contact with animals, and childcare attendance. Despite its public health importance, the number of people who become infected each year is not known. In 1997, active surveillance for C. parvum was added to the Foodborne Diseases Active Surveillance Network (FoodNet), a collaborative effort among the Centers for Disease Control and Prevention, selected state health departments, the U.S. Departments of Agriculture and Food and Drug Administration. During the first 2 years of surveillance, 1,023 laboratory-confirmed cases of cryptosporidiosis were detected in FoodNet (Connecticut, Minnesota, Oregon, and selected counties in California, Georgia, Maryland, and New York). The annual rate per 100,000 persons was 2.3. Sixteen percent of case-patients were hospitalized. A seasonal increase in case detection was noted in late summer among persons less than 15 years of age. These data represent the first active multistate ascertainment of laboratory-confirmed cryptosporidiosis cases and provide useful information on the burden of disease in the United States.

Adolescent↗
PubMed2000

Effect of the factor V Leiden mutation on the clinical expression of severe hemophilia A.

To determine whether the factor V Leiden mutation is associated with decreased bleeding in individuals with severe hemophilia A, factor concentrate utilization, maximum annual number of bleeding episodes, and the prevalence of hemophilic arthropathy between carriers and non-carriers of the factor V Leiden mutation were compared. Heterozygosity for the factor V Leiden mutation was found in 6 of 137 subjects (4.4%). Carriers of the factor V Leiden mutation utilized less factor concentrate (geometric mean: 310 vs. 1185 units/kg/year) and had fewer bleeding episodes than non-carriers (proportion with 10 or fewer bleeding episodes in their worst year: 50 vs. 11%). However, the factor V Leiden mutation was not associated with the absence of arthropathy. The intron 22 inversion mutation of the factor VIII gene was tested for in a subgroup of 80 subjects, but it was not found to be a significant variable for any of the bleeding endpoints. The results of this small study are consistent with the hypothesis that the factor V Leiden mutation imparts a protective effect; however, a larger confirmatory study in which the factor VIII molecular defects can be controlled for is needed. Furthermore, most severe hemophiliacs who used fewer than 200 units/kg/year of factor concentrate or who had experienced 10 or fewer bleeding episodes per year did not carry the factor V Leiden mutation, suggesting that the proportion of severe hemophiliacs whose mild clinical course can be attributed to the factor V Leiden mutation is small.

Adolescent↗
PubMed2000

Application of pericardial graft in the surgical management of Peyronie's disease.

PURPOSE: We investigated the use of Tutoplast cadaveric pericardium as an alternative material for grafting the tunica albuginea defect after Peyronie's plaque excision. MATERIALS AND METHODS: A total of 11 patients with significant penile curvature interfering with sexual intercourse were evaluated after at least 12 months of conservative therapy. Preoperative evaluation in all cases included penile duplex Doppler ultrasound studies. Chemically processed and gamma irradiated pericardium was used to graft the cavernosal defect after surgical excision of the penile plaque. In 3 patients a penile prosthesis was simultaneously placed secondary to documented erectile dysfunction at duplex Doppler ultrasound evaluation. RESULTS: Penile curvature resolved in all patients, allowing for normal sexual function after a mean followup of 14 months (range 9 to 19). No postoperative evidence of tissue rejection or infection was noted. In 1 patient urethro-corporal communication developed and a single penile cylinder was explanted. Another patient had a mild dorsal bulge at the site of graft placement when the prosthesis was fully inflated. CONCLUSIONS: Polymeric silicone material used to provide satisfactory results in the surgical treatment of Peyronie's disease but it is no longer available for biomedical use. We demonstrate the effective use of cadaveric pericardium as a graft material for cavernosal defects after Peyronie's plaque excision. Overall patient satisfaction, absence of a second surgical incision, relative low risk and ease of surgical placement make this material ideal for the surgical treatment of this disease process.

Adult↗
PubMed2000

Anaesthesia for caesarean section in a patient with Eisenmenger's syndrome.

Eisenmenger's syndrome was originally described in 1897 and redefined by Wood in 1958. This syndrome includes pulmonary hypertension with reversed or bi-directional shunt associated with septal defects or a patent ductus arteriosus. A 27-year-old G2 PO with Eisenmenger's syndrome presented to the hospital for management at 17 weeks of pregnancy. She was advised termination of pregnancy but she refused. An elective caesarean section was performed successfully under general anaesthesia uneventfully at 29 weeks due to severe intrauterine growth retardation (IUGR). Patient's postoperative complications like pulmonary thromboembolism, the advantages and disadvantages of anticoagulation are discussed. Pregnancy carries substantial maternal and fetal risk for patients with pulmonary hypertension and Eisenmenger's syndrome. Although pregnancy should be discouraged in women with Eisenmenger's syndrome it can be successful.

Adult↗
PubMed1999

Mitogen-activated protein kinase regulates transcription of the ApoCIII gene. Involvement of the orphan nuclear receptor HNF4.

The transcriptional regulation of the apoCIII gene by hormonal and metabolic signals plays a significant role in determining plasma triglyceride levels. In the current work we demonstrate that the apoCIII gene is regulated by the mitogen-activated protein (MAP) kinase signaling pathway. In HepG2 cells, repression of MAP kinase activity by treatment with the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD98059 caused a 5-8-fold increase in apoCIII transcriptional activity. Activation of MAP kinase by phorbol ester treatment caused a 3-5-fold reduction in apoCIII transcription. The region of the apoCIII promoter responsible for this regulation was mapped in transiently transfected HepG2 cells to a 6-base pair element located at -740. The major protein binding to this site was identified as the nuclear hormone receptor HNF4. An increase in HNF4 mRNA and protein levels was observed in HepG2 cells after treatment with PD98059, indicating that the MAP kinase pathway regulates the expression of the HNF4 gene. These findings demonstrate that the apoCIII gene can be regulated by signals acting through the MAP kinase pathway and that this regulation is mediated, at least in part, by changes in the amount of HNF4.

Apolipoprotein C-III↗
PubMed1999

Review of methods to predict and detect atrial fibrillation in post-cardiac surgery patients.

Atrial fibrillation (AF) is the most common sustained arrhythmia after cardiac surgery. Postoperative AF is known to substantially lengthen hospital stay and affect patient recovery. Identification of those at risk of developing AF after surgery and early detection of AF during recovery would be extremely helpful in effective management of these patients, including targeting prophylactic therapy to prevent AF in high-risk patients. In this communication, diagnostic methods to identify those at risk of developing AF after surgery and early identification of AF before, during, and after surgery have been reviewed. Signal-averaged P wave analysis, done before surgery, identifies patients who are likely to develop AF during recovery. When combined with low ejection fraction, signal-averaged P wave can discriminate those who develop AF from those who do not. During recovery, AF can be detected early either from a detailed analysis of atrial activity in a 10-second electrocardiogram or an analysis of R-to-R intervals from an extended rhythm strip (1 minute or longer). Analysis of the 10-second electrocardiogram includes median QRST subtraction from rhythm data and detection and analysis of atrial signals in the resulting residual. AF is detected from extended rhythm strips by using a statistical model to identify the presence of characteristic irregular patterns of R-to-R intervals.

Atrial Fibrillation↗
PubMed1999

Heparin-surface-modified intraocular lenses in pediatric cataract surgery: prospective randomized study.

PURPOSE: To evaluate the performance of heparin-surface-modified (HSM) intraocular lenses (IOLs) in pediatric eyes after cataract surgery. SETTING: L.V. Prasad Eye Institute, Hyderabad, India. METHODS: This prospective, randomized, double-masked, controlled clinical trial comprised 90 children aged 2 to 14 years with cataract. The patients were consecutively randomized to receive an HSM (Group 1) or an unmodified (Group 2) poly(methyl methacrylate) (PMMA) IOL. Extracapsular cataract extraction (ECCE) with IOL implantation was performed in children 8 years and older and ECCE with primary posterior capsulotomy, anterior vitrectomy, and IOL implantation in children younger than 8 years. Outcome parameters were inflammatory cell deposits on the IOL surface, posterior synechias, and anterior chamber reaction. RESULTS: Follow-up data were available for 73, 70, 60, and 68 patients at 1 week, 1 month, 3 months, and 6 months, respectively. Significantly fewer cell deposits were noted in Group 1 at 1, 3, and 6 months (P < .001). Synechia formation and anterior chamber reaction were comparable in the 2 groups. CONCLUSION: The lower incidence of inflammatory cell deposit formation in eyes with HSM PMMA IOLs indicates that these IOLs have greater bicompatibility than unmodified IOLs in pediatric cataract surgery.

Adolescent↗
PubMed1999

A high sucrose, high linoleic acid diet potentiates hypertension in the Dahl salt sensitive rat.

Insulin resistance can be induced by diets high in simple carbohydrates or fatty acids. To determine whether these nutrients also affect arterial pressure in genetic models of salt sensitive and salt resistant hypertension, Dahl salt sensitive (S) and salt resistant (R) rats were each fed the following isocaloric diets containing 3% NaCl for 4 weeks (10 rats/group): 1) control; 2) high sucrose (60%); 3) high linoleic acid (LA, provided as 10% safflower oil); and 4) high sucrose plus high LA. Tail systolic blood pressures (SBP) were measured weekly, and at 4 weeks, direct mean arterial pressures (MBP) were measured in conscious animals. Insulin sensitivity was assessed by in vitro uptake of tritiated glucose by adipocytes in response to graded doses of insulin. Weight gain did not differ among groups. High sucrose alone and high LA alone did not affect blood pressure in either strain. However, SBP and MBP were increased (P < .05) by the high sucrose plus high LA diet in Dahl-S but not in Dahl-R rats. Sucrose alone and LA alone decreased (P < .05) insulin sensitivity in Dahl-S and Dahl-R rats. In both strains, sucrose plus LA decreased insulin sensitivity to a greater extent (P < .05) than sucrose alone or LA alone. Thus, the sucrose plus LA diet decreased insulin sensitivity in both Dahl-S and Dahl-R rats, whereas blood pressure was increased only in Dahl-S rats. The phenotype of elevated arterial pressure is influenced both by a genetic-nutrient interaction and by an interaction among specific nutrients resulting in insulin resistance.

Adipocytes↗
PubMed1999

Adherence of Acanthamoeba to human corneal epithelial cells recovered from normal non-lens wearers and asymptomatic contact lens wearers.

To increase our knowledge of factors leading to Acanthamoeba keratitis in contact lens wearers, we determined the ability of this organism to adhere to corneal epithelial cells (EC) recovered from non-lens wearers (NL) and from subjects using hydrogel contact lenses on a daily (DW) and extended wear (EW) schedule. ECs were incubated with trophozoites of Acanthamoeba and, after 3 h, the median per cent of cells exhibiting adherence was 24, 23 and 23 for NL, DW and EW groups respectively (P=0.552, Kruskal-Wallis Test). There were no differences between the groups for the number of adherent amoebae and a significant majority had only one adherent trophozoite per EC. No difference in adherence was seen with increasing exposure time. Factors other than amoebic adherence to superficial corneal EC are responsible for the increased incidence of Acanthamoeba keratitis in lens wearers.

Journal Article↗