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Biomedical subjects

G Singh

Publications and source records attributed to G Singh.

At least 19 recordsLinked to original sources
PubMed2007

A likelihood approach to estimating sensitivity and specificity for binocular data: application in ophthalmology.

Binocular data typically arise in ophthalmology where pairs of eyes are evaluated, through some diagnostic procedure, for the presence of certain diseases or pathologies. Treating eyes as independent and adopting the usual approach in estimating the sensitivity and specificity of a diagnostic test ignores the correlation between eyes. This may consequently yield incorrect estimates, especially of the standard errors. The paper proposes a likelihood-based method of accounting for the correlations between eyes and estimating sensitivity and specificity using a model for binocular or paired binary outcomes. Estimation of model parameters via maximum likelihood is outlined and approximate tests are provided. The efficiency of the estimates is assessed in a simulation study. An extension of the methodology to the case of several diagnostic tests, or the same test measured on several occasions, which arises in multi-reader studies, is given. A further extension to the case of multiple diseases is outlined as well. Data from a study on diabetic retinopathy are analysed to illustrate the methodology.

Canada↗
PubMed2007

Presence or absence of lipopolysaccharide O antigens affects type III secretion by Pseudomonas aeruginosa.

Pseudomonas aeruginosa is one of the major causative agents of mortality and morbidity in hospitalized patients due to a multiplicity of virulence factors associated with both chronic and acute infections. Acute P. aeruginosa infection is primarily mediated by planktonic bacteria expressing the type III secretion system (TTSS), a surface-attached needle-like complex that injects cytotoxins directly into eukaryotic cells, causing cellular damage. Lipopolysaccharide (LPS) is the principal surface-associated virulence factor of P. aeruginosa. This molecule is known to undergo structural modification (primarily alterations in the A- and B-band O antigen) in response to changes in the mode of life (e.g., from biofilm to planktonic). Given that LPS exhibits structural plasticity, we hypothesized that the presence of LPS lacking O antigen would facilitate eukaryotic intoxication and that a correlation between the LPS O-antigen serotype and TTSS-mediated cytotoxicity would exist. Therefore, strain PAO1 (A+ B+ O-antigen serotype) and isogenic mutants with specific O-antigen defects (A+ B-, A- B+, and A- B-) were examined for TTSS expression and cytotoxicity. A strong association existed in vitro between the absence of the large, structured B-band O antigen and increased cytotoxicity of these strains. In vivo, all three LPS mutant strains demonstrated significantly increased lung injury compared to PAO1. Clinical strains lacking the B-band O antigen also demonstrated increased TTSS secretion. These results suggest the existence of a cooperative association between LPS O-antigen structure and the TTSS in both laboratory and clinical isolates of P. aeruginosa.

Animals↗
PubMed2006

Characterization of the snake venom ligand [125I]-DNP binding to natriuretic peptide receptor-A in human artery and potent DNP mediated vasodilatation.

BACKGROUND AND PURPOSE: The natriuretic peptides, ANP and BNP, modulate vascular smooth muscle tone in human conduit arteries. Surprisingly, the natriuretic peptide receptor-A (NPR-A) has not been visualized using radioligand binding in these vessels. A new member of this peptide family, Dendroaspis natriuretic peptide (DNP) identified from snake venom, has been proposed to be present in human plasma and endothelial cells. Also, recently a novel radioligand, [(125)I]-DNP, has been characterized as selective for NPR-A in human heart. EXPERIMENTAL APPROACH: Our aims were to investigate expression and function of NPR-A receptors in human mammary artery using [(125)I]-DNP to quantify receptor density, immunocytochemistry to delineate the cellular distribution of the receptor and in vitro pharmacology to compare DNP induced vasodilatation to that of ANP. KEY RESULTS: Saturable, sub-nanomolar affinity [(125)I]-DNP binding was detected to smooth muscle of mammary artery, with receptor density of approximately 2 fmol mg(-1) protein, comparable to that of other vasoactive peptides. NPR-A immunoreactivity was localised to vascular smooth muscle cells and this was confirmed with fluorescence dual labelling. NPR-A expression was not detected in the endothelium. Like ANP, DNP fully reversed the constrictor response to ET-1 in endothelium intact or denuded mammary artery, with comparable nanomolar potencies. CONCLUSIONS AND IMPLICATIONS: This is the first characterization of NPR-A in human mammary artery using [(125)I]-DNP and we provide evidence for the presence of receptor protein on vascular smooth muscle cells, but not endothelial cells. This implies that the observed vasodilatation is predominantly mediated via direct activation of smooth muscle NPR-A.

Adrenomedullin↗
PubMed2006

Treatment of neurocysticercosis: current status and future research needs.

Here we put forward a roadmap that summarizes important questions that need to be answered to determine more effective and safer treatments. A key concept in management of neurocysticercosis is the understanding that infection and disease due to neurocysticercosis are variable and thus different clinical approaches and treatments are required. Despite recent advances, treatments remain either suboptimal or based on poorly controlled or anecdotal experience. A better understanding of basic pathophysiologic mechanisms including parasite survival and evolution, nature of the inflammatory response, and the genesis of seizures, epilepsy, and mechanisms of anthelmintic action should lead to improved therapies.

Anticonvulsants↗
PubMed2006

The prevalence of anaemia depends on the definition: an example from the Aboriginal Birth Cohort Study.

OBJECTIVE: The cutoffs defining anaemia based on haemoglobin and haematocrit recommended by the World Health Organization (WHO) and the United States (US) are different. We compared the prevalences resulting from these definitions and explored the reasons for the variation observed. DESIGN: A cross-sectional survey within a cohort study of children recruited at birth at Royal Darwin Hospital. SETTING: Subjects were interviewed in their homes or other convenient location and had a blood sample drawn. SUBJECTS: Five hundred and seventeen Australian Aboriginal children aged 9-13 years inclusive. RESULTS: Depending on the criterion used, the prevalence of anaemia in the total group ranged between 6% (95% confidence interval: 4.1-8.4%) and 24.4% (20.7-28.3). Using the WHO criteria, girls aged 12-13 years were identified as a target group, having a two- to-six fold higher prevalence than the other groups. When compared to the US criteria, boys aged 12-13 years had the highest prevalence of anaemia, although this was not significant. Simulations show that the WHO cutoffs are based on inconsistent centiles of the age-sex haemoglobin and haematocrit distributions, and that this largely explains the discrepant results. CONCLUSIONS: This variability in definition could lead to inappropriate identification of target groups for intervention programmes.

Adolescent↗
PubMed2006

Study on oxidative stress in patients with abdominal trauma.

Reactive oxygen species have been implicated in the etiology of multiple organ dyspepsia syndrome and infection's complications in patients with trauma. But the oxidative stress and antioxidants levels in abdominal trauma have not yet been studied. Therefore, this study was planned to measure lipid peroxidation for oxidative stress and reduced glutathione, catalase and superoxide dismutase (SOD) for antioxidant levels in plasma & heamolysate of 30 patients with abdominal trauma and 30 controls. From this study we can summarize that there was an increase in oxidative stress and decrease in antioxidant levels (causing oxidative stress) on day zero in patients with abdominal trauma. This oxidative stress on day zero was not related to the development of complications. There was no significant difference in oxidative stress between patients with solitary and multiple abdominal organ injury and also between patients with hollow viscus injury and solid organ injury on day zero. From this study, we conclude that in patients with abdominal trauma there was increase in oxidative stress and decrease in antioxidant levels on day zero.

Abdominal Injuries↗
PubMed2006

Effects of geldanamycin on HIF-1alpha mediated angiogenesis and invasion in prostate cancer cells.

Geldanamycin (GA), a benzoquinone ansamycin, is a naturally occurring inhibitor of heat shock protein (Hsp90), which regulates the transcription activity of hypoxia-inducible factor 1 (HIF-1alpha). Under hypoxia, HIF-1alpha is activated in tumor cells, and induces the transcription of vascular endothelial growth factor (VEGF), which is the prime regulator for angiogenesis. VEGF promotes the formation of new blood vessels by stimulating endothelial cell division and migration. This eventually forms a vascular network that allows for tumor growth and metastasis. In this study, we used GA to inhibit HIF-1alpha transcription function. Human prostate cancer DU-145 cells were incubated in a hypoxic chamber at 1% O(2) and 37 degrees C for different durations. Both mRNA and protein levels of HIF-1alpha and VEGF were upregulated under hypoxic conditions. We demonstrated that GA treatment of hypoxic DU-145 cells abolished the induction of HIF-1alpha protein in a time-dependent manner and decreased VEGF mRNA and its protein levels. The transient transfection of DU-145 cells with luciferase reporter gene construct (5HRE/hCMVmp-luc) showed that the transcriptional activity of HIF-1alpha was significantly induced in response to hypoxia, but inhibited by GA. In addition, using conditioned medium from GA-treated hypoxic cells led to a significant decrease in cell invasion in comparison with using conditioned medium from nontreated hypoxic cells. These data provide evidence for the important role of GA in inhibition of angiogenesis and also invasion mediated by HIF-1alpha in prostate cancer cells.

Benzoquinones↗
PubMed2006

Chronic lymphocytic leukaemia, synchronous small cell carcinoma and squamous neoplasia of the urinary bladder in a paraplegic man following long-term phenoxybenzamine therapy.

STUDY DESIGN: A case report. OBJECTIVE: To raise awareness among spinal cord clinicians of the possible carcinogenic effect of phenoxybenzamine and of the rare occurrence of small cell carcinoma in the neuropathic bladder. SETTING: Regional Spinal Injuries Centre and District General Hospital, Southport, Merseyside, United Kingdom. CASE REPORT: A 28-year-old man sustained a fracture dislocation of L-1 with consequent paraplegia (ASIA impairment scale A). Phenoxybenzamine treatment enabled his indwelling catheter to be discarded in favour of a penile sheath, but it caused unacceptable dizziness and was stopped after 7 years. After 20 years, he developed chronic lymphocytic leukaemia, which was treated with chlorambucil and fludarabine. After 2 years, investigation of bilateral hydronephrosis revealed a primary small cell carcinoma of the bladder with coexistent squamous dysplasia. Uraemia supervened and, declining active treatment, the patient died 3 weeks after diagnosis. CONCLUSION: Phenoxybenzamine, a known carcinogen in rodents, is likely also to be carcinogenic in humans, and patients with spinal cord injury who have received the drug for any significant period of time, need close follow-up to allow early detection of cancer. Phenoxybenzamine should not be prescribed on a long-term basis, and should instead be replaced with a selective alpha-blocker.

Adult↗
PubMed2006

Brief overview of maternal triglycerides as a risk factor for pre-eclampsia.

BACKGROUND: Features of the metabolic syndrome-maternal obesity, diabetes mellitus and chronic hypertension-are risk factors for pre-eclampsia. OBJECTIVES: To determine the risk of pre-eclampsia in the presence of maternal hypertriglyceridemia, another major element of the metabolic syndrome. SEARCH STRATEGY: Two investigators independently searched PubMed and Embase databases from 1980 to December 2004 for relevant studies. The terms preeclampsia, eclampsia, pregnancy-induced hypertension or toxemia were combined with dyslipidemia, hyperlipidemia, hypertriglyceridemia, lipids, cholesterol, triglycerides (TG) or lipoprotein. SELECTION CRITERIA: We included case-control and cohort studies published in English that included at least 20 women with pre-eclampsia and that sampled serum or plasma TG at any time before, during or after pregnancy. DATA COLLECTION AND ANALYSIS: Mean maternal TG concentrations were compared between cases and controls within each study. The odds ratio of pre-eclampsia was calculated by comparing the risk of pre-eclampsia among women in each higher TG concentration category with that in the lowest reference category. MAIN RESULTS: A total of 19 case-control and 3 prospective cohort studies were included. In 14 studies, the mean TG concentration was significantly higher among pre-eclamptic cases than among unaffected controls; in seven other studies, there was a nonsignificant trend in the same direction. The risk of pre-eclampsia typically doubled with each increasing TG category. In the four studies that adjusted for potential confounders, such as maternal age, parity and body mass index, there was about a four-fold higher risk of pre-eclampsia in the highest relative to the lowest TG category. AUTHOR'S CONCLUSIONS: There exists a consistent positive association between elevated maternal TG and the risk of pre-eclampsia. Given that maternal hypertriglyceridemia is a common feature of the metabolic syndrome, interventional studies are needed to determine whether pre-pregnancy weight reduction and dietary modification can lower the risk of pre-eclampsia.

Biomarkers↗
PubMed2006

Epidemiologic classification of seizures associated with neurocysticercosis: observations from a sample of seizure disorders in neurologic care in India.

AIMS: To determine the etiologic role of neurocysticercosis (NC) in a hospital-based sample of epilepsies divided according to International League Against Epilepsy (ILAE) epidemiological criteria and number of seizures prior to presentation. METHODS: A sample comprising 1026 consecutive patients with either definite seizures or epilepsy attending a Neurology Outpatient Service was divided into four subgroups: single seizure (n = 314), incident epilepsy (n = 127), prevalent epilepsy (n = 398) and recurrent acute symptomatic seizures (RASS) (n = 175). The etiologic contribution of NC to each of the subgroups was examined with imaging studies. RESULTS: Neurocysticercosis was diagnosed on imaging studies in 34.6% of patients with seizure disorder of any type, 59.2% of those with a single seizure, 23.7% of those with recurrent seizure disorder, 92.0% of those with RASS, none of cases of incident epilepsy and 2.0% with prevalent epilepsy. A diagnosis of NC was significantly associated with single seizures (P < 0.001). CONCLUSIONS: Imaging abnormalities consistent with NC are frequently noted in persons presenting with a single seizure in neurologic care in NC-endemic countries like India. The probability of diagnosing NC diminishes with increasing numbers of seizures. Among samples of individuals with recurrent-unprovoked seizures, it is rare for imaging to demonstrate lesions of NC.

Adolescent↗
PubMed2006

Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data.

Due to increasing use of allografts from donation after cardiac death (DCD) donors, we evaluated DCD liver transplants and impact of recipient and donor factors on graft survival. Liver transplants from DCD donors reported to UNOS were analyzed against donation after brain death (DBD) donor liver transplants performed between 1996 and 2003. We defined a recipient cumulative relative risk (RCRR) using significant risk factors identified from a Cox regression analysis: age; medical condition at transplantation; regraft status; dialysis received and serum creatinine. Graft survival from DCD donors (71% at 1 year and 60% at 3 years) were significantly inferior to DBD donors (80% at 1 year and 72% at 3 years, p < 0.001). Low-risk recipients (RCRR < or = 1.5) with low-risk DCD livers (DWIT < 30 min and CIT < 10 h, n = 226) achieved graft survival rates (81% and 67% at 1 and 3 years, respectively) not significantly different from recipients with DBD allografts (80% and 72% at 1 and 3 years, respectively, log-rank p = 0.23). Liver allografts from DCD donors may be used to increase the cadaveric donor pool, with favorable graft survival rates achieved when low-risk grafts are transplanted in a low-risk setting. Whether transplantation of these organs in low-risk recipients provides a survival benefit compared to the waiting list is unknown.

Cadaver↗
PubMed2006

Subtenons infection by Dirofilaria repens.

Zoonotic filariasis caused by Dirofilaria repens, a parasite of carnivores occurs mainly in countries surrounding Mediterranean region. The infection occurs in and around eye among animal handlers through vector transmission. We are reporting a case of human Dirofilariasis affecting subtenons region in a 63 year-old woman from Coimbatore, South India. The purpose of this article is to review the clinical course and management of ocular Dirofilariasis.

Animals↗