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Biomedical subjects

N Singh

Publications and source records attributed to N Singh.

At least 217 records · Page 12Linked to original sources

Adherence of human immunodeficiency virus-infected patients to antiretroviral therapy.

The impact of demographic, psychosocial, and medical regimen-related variables on adherence of 123 human immunodeficiency virus (HIV)-infected patients to antiretroviral therapy was assessed by means of refill methodology. Satisfaction with social support (P = .029), problem-focused coping (P = .027), and active-behavioral coping (P = .011) correlated significantly with adherence, whereas loss of motivation (P = .006), hopelessness (P = .16), and avoidant coping (p = .015) correlated with nonadherence. At the 6-month follow-up, the mean CD4 cell count differed significantly among adherent versus nonadherent patients (a mean increase of 78/mm3 vs. a mean decrease of 5/mm3; P = .018). Adherence did not correlate with the number of antiretroviral medications consumed per day (mean, 3.0 vs. 2.5). Non-Caucasian patients were more likely to be nonadherent than Caucasian patients (relative risk, 2.5; 95% confidence interval, 1.2-5.3; P = .013); this difference was not explained by age, education, employment, income, history of intravenous drug use, or medical regimen. Non-Caucasian patients, however, were less satisfied with their social support (P = .04) and informational support (P = .016) and were more likely to utilize emotion-focused coping (P = .01). Thus, satisfaction with social support and coping style significantly impacted adherence and likely accounted for the observed racial difference in adherence among HIV-infected patients.

Adaptation, Psychological↗

Chemopreventive effect of 4'-demethyl epipodophyllotoxin on DMBA/TPA-induced mouse skin carcinogenesis.

The chemopreventive effect of topical application of 4'-demethyl epipodophyllotoxin (DMEP), an antimitotic agent, on a two-stage skin carcinogenesis model in Swiss Albino mice induced by 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) was investigated. Two topical applications with 0.24% DMBA over 1 week, followed later by 5 nmol of TPA twice weekly produced 100% incidence of tumors in these animals by 18 weeks. Treatment of animals with DMEP (until the end of the experiment), 30 min before TPA treatment, significantly reduced the tumor incidence, tumor volume and the conversion efficiency of papillomas to squamous cell carcinomas. The tumor formation and growth was also delayed by DMEP pre-treatment. Application of DMEP protected against the losses provoked in levels of glutathione and activity of catalase and superoxide dismutase in skin and liver of animals by the application of DMBA/TPA. Thus, DMEP might possibly be exerting its chemopreventive activity by acting as an antioxidant.

9,10-Dimethyl-1,2-benzanthracene↗

Peptide dependency of alloreactive CD4+ T cell responses.

Alloreactivity, the capacity of a large number of T lymphocytes to react with foreign MHC molecules, represents the cellular basis for the rejection of tissue grafts. Although it was originally assumed that the TCR of alloreactive T cells focus their recognition on the polymorphic residues that differ between the MHC molecules of responder and stimulator cells, studies in the MHC class I system have clearly demonstrated that MHC-bound peptides can influence this interaction. It remains unclear, however, whether peptides play an equally important role for the recognition of MHC class II molecules by alloreactive CD4+ T cells. Another issue that remains unresolved is the overall frequency of peptide-dependent versus peptide-independent alloreactive T cells. We have addressed these questions with antigen-presenting cells (APC) from H2-M mutant mice that predominantly express a single MHC class II-peptide complex, H2-Ab bound by a peptide (CLIP) derived from the class II-associated invariant chain. APC from these mice were used as targets and stimulators for alloreactive CD4+ T cells. Results demonstrated that the vast majority of CD4+ alloreactive T cells recognize MHC class II molecules in a peptide-dependent fashion.

Amino Acid Sequence↗

Infections in solid organ transplant recipients.

A disturbing trend in evolution for sometime has culminated in the fact that resistant Gram-positive bacteria including enterococci and staphylococci have emerged as the leading pathogens at many transplant centers. Recently published reports have highlighted the formidable challenge such antimicrobial-resistant microorganisms now pose in transplant recipients. Studies published within the past year have documented the clinical relevance of human herpesvirus-6 after transplantation, as well as the transmission of human herpesvirus-8 by transplanted allograft and the subsequent development of Kaposi's sarcoma in these patients. A novel hepatitis virus has been discovered; studies to elucidate its significance in the transplant setting are underway.

Journal Article↗

Benign familial neonatal epilepsy with mutations in two potassium channel genes.

The significant progress made over the past year in understanding the basis for a form of neonatal seizures can be attributed to the successful positional cloning of two new voltage-gated potassium channel genes. Expression studies have increased our understanding of the biology of these channels and their role in epilepsy.

Chromosomes, Human, Pair 20↗

Lipid antigen presentation in the immune system: lessons learned from CD1d knockout mice.

CD1 molecules represent a distinct lineage of antigen-presenting molecules that are evolutionarily related to the classical major histocompatibility complex (MHC) class I and class II molecules. Unlike the classical MHC products that bind peptides, CD1 molecules have evolved to bind lipids and glycolipids. Murine and human CD1d molecules can present glycolipid antigens such as alpha-galactosylceramide (alpha-GalCer) to CD1d-restricted natural killer (NK) T cells. Using CD1d knockout mice we demonstrated that CD1d expression is required for the development of NK T cells. These animals were also deficient in the rapid production of interleukin-4 and interferon-gamma in response to stimulation by anti-CD3 antibodies. Despite these defects, CD1d knockout animals were able to generate strong T-helper type 1 (TH1) and TH2 responses. Spleen cells from these animals neither proliferated nor produced cytokines in response to stimulation by alpha-GalCer. Repeated injection of alpha-GalCer into wild-type but not CD1d mutant mice was able to clear metastatic tumors. We further showed that alpha-GalCer can inhibit disease in diabetes-prone non-obese diabetic mice. Collectively, these findings with CD1d knockout animals indicate a critical role for CD1d-dependent T cells in various disease conditions, and suggest that alpha-GalCer may be useful for therapeutic intervention in these diseases.

Animals↗

A clinical and histopathological study of macular type of post-kala-azar dermal leishmaniasis.

Post-kala-azar dermal leishmaniasis (PKDL) is an uncommon sequel seen in patients with a previous attack of kala-azar (KA). It is characterized by hypopigmented macules and erythematous eruptions leading to the formation of papules, plaques and nodules. Little attention has been paid to the rare group of patients who present with only hypopigmented macules. The present study has described the distribution of lesions in macular PKDL and their histopathology.

Adolescent↗

The effect of glutamate uptake inhibitors on hippocampal evoked potentials in vitro.

The influence of four inhibitors of the high-affinity glutamate uptake system (DL-aspartic acid beta-hydroxymate, DL-AHM; L-aspartic acid beta-hydroxymate, L-AHM; threo-beta-methylaspartate, DLM; L-transpyrrolidine-2, 4-dicarboxylate, PDC) on potentials recorded from hippocampal slices was investigated. At low concentrations of DL-AHM, L-AHM and DLM (50-150 microM) the population spike was permanently amplified. NMDA receptor antagonists blocked this facilitatory effect of L-AHM, DL-AHM and DLM. At higher concentrations (400-700 microM) DL-AHM and DLM abolished the population spike, while L-AHM did not eliminate the population spike at any concentration tested. None of these uptake inhibitors influenced an antidromic potential recorded in Ca(2+)- free Ringer solution. PDC at lower concentrations (75 microM) did not affect the population spike and at higher concentrations (150 microM-500 microM) induced only a transient elevation in population spike. Our data demonstrate that modification of glutamate uptake may be an important factor in the regulation of synaptic efficiency of glutamergic pathways.

Animals↗

Role of caspases in apoptosis and disease.

Apoptosis, a genetically governed process of eliminating cells in response to a variety of stimuli provides protection against cancer and viral infections as well as maintains homeostasis. Recent studies using both molecular and cloning approaches, and in vitro systems have identified a class of highly specific proteases, termed caspases, that appear to have an important role in apoptotic execution. Caspases are synthesized as precursor molecules that require processing at specific aspartate residues to produce the active enzyme which in turn leads to the cleavage of various death substrates that lead to morphological changes typical of apoptosis. This review discusses caspases, their inhibitors and regulators. Since cytotoxic drugs used in chemotherapy of leukemia's and solid tumors cause apoptosis in target cells, elucidating the consequences of proteolytic activity occupies a central role for understanding of the molecular mechanism of apoptosis which can help us to use the caspase inhibitors as targets of therapy.

Apoptosis↗

The Guillain-Barré syndrome following dengue fever.

A 44 year old female presented with fever, muscle aches, rash and a low platelet count. IgM antibody to dengue virus was positive. Two weeks later she developed a flaccid areflexic quadriparesis. Nerve conduction studies showed a predominantly demyelitinating sensory motor polyneuropathy consistent with Guillain-Barré syndrome. Despite the relatively common occurrence of dengue fever, an associated polyradiculoneuropathy is distinctly uncommon.

Adult↗

Impact and inequity of inpatient waiting times for advanced cardiovascular services in community hospitals across the greater Toronto area.

OBJECTIVE: To assess waiting times for inpatients requiring urgent transfer for advanced cardiovascular procedures from community hospitals; the magnitude of adverse events while waiting; and possible inequity among community hospitals in access to these services. SETTING: Seven representative community hospitals in the Greater Toronto Area (GTA). DESIGN: Prospective data collection over 12 months (May 1997 to April 1998). PATIENTS: One thousand, two hundred and three inpatients who waited a total of 7261 hospital days for advanced cardiovascular procedures. MAIN RESULTS: The average (+/- SD) inpatient waiting time, in days, for catheterization was 5.7+/-1.3, angioplasty 5.8+/-2.1, bypass surgery 7.0+/-2.1 and pacemakers 4.2+/-1.6. During this time there were 14 deaths (1.2%) and 12 (1.0%) morbid events in-hospital. Extrapolation of these data to all 21 community hospitals in the GTA suggests that annually 21,783 bed days are used by inpatients awaiting transfer for advanced cardiovascular procedures, during which time 42 fatal and 36 morbid events can be expected to occur. Of the seven hospitals, one had a catheterization laboratory (group 1), two had no laboratory but had catheterizing cardiologists (group 2), and four had no laboratory and no catheterizing cardiologists (group 3). None of these hospitals had on-site revascularization facilities. The average number of days spent waiting for catheterization in group 1 (3.1+/-0.4) was significantly less than that in group 2 (5. 4+/-1.3, P<0.001) and group 3 (6.5+/-1.3, P<0.0001). The catheterization wait in group 2 was significantly less than that in group 3 (P<0.02). There were no significant differences among the three groups in the number of days spent waiting for angioplasty or bypass surgery. CONCLUSION: Waiting times for inpatients requiring advanced cardiovascular procedures in GTA community hospitals are long, and are associated with substantial morbidity and mortality. These waiting times also promote inefficient bed use and increased health care costs. Furthermore, these data suggest that access to inpatient coronary angiography in the GTA is inequitable and appears to depend more on the presence of on-site catheterization laboratories or catheterizing cardiologists than on illness severity.

Cardiovascular Diseases↗

Quality of life in patients with human immunodeficiency virus infection: impact of social support, coping style and hopelessness.

We aimed to determine whether the quality of life (QOL) in the patients infected with human immunodeficiency virus (HIV) infection was influenced by satisfaction with social support, coping style and hopelessness. One hundred and thirty-eight HIV-infected patients were prospectively studied in this multicentre, longitudinal study. The QOL was assessed by Medical Outcome Study Health Survey SF-36, social support by Sarason Social Support Questionnaire, hopelessness by Beck Hopelessness Scale, and coping by Billing and Moos Inventory of coping with illness. The QOL did not correlate with age, sex, race, HIV risk factor, education or marital status. Employment (P = 0.0001), higher income (P = 0.03), satisfaction with social support (P = 0.04), regardless of the source of that support, and problem-focused coping (P = 0.03) were associated with a significantly better QOL, while, emotion-focused coping (r = -0.19, P = 0.04), avoidant coping (r = 0.40, P = 0.0001), hopelessness (r = -0.64, P = 0.0001) and AIDS (P = 0.09) were predictors of poorer QOL. Physical functioning correlated positively with employment (P = 0.0001), and inversely with AIDS (P = 0.0002), hopelessness (P = 0.03), avoidant coping (P = 0.03), and age (P = 0.10). At 6 months follow up, QOL score had changed in 20% of the patients; older age (P = 0.01), and lesser satisfaction with social support (P = 0.15) were associated with a decline in QOL, while adherence with antiretroviral therapy (P = 0.006) was associated with an increase in QOL score. Seven of 138 patients died during follow up; these patients had significantly lower QOL at baseline than all other patients (P = 0.003). Interventions to alleviate hopelessness, maladaptive coping, and enhancement of satisfaction with social support may improve overall QOL in HIV-infected patients. Older patients with HIV were less satisfied with their social support, were more likely to utilize unhealthy coping styles, and experienced a greater decline in QOL over time.

Adult↗

Evaluation of a rapid test for the detection of antibodies to human immunodeficiency virus type 1 and 2.

Hema-Strip HIV-1/2 is a one-step rapid test for the detection of anti-HIV-1/2 antibodies in whole blood. The test requires no expensive equipment and the results are available within 10-15 min. Using 72 known HIV-1 positive samples and 780 high-risk prisoners, the sensitivity and specificity of Hema-Strip HIV-1/2 was found to be comparable to microparticle enzyme immunoassay (MEIA). The data also indicated that Hema-Strip HIV-1/2 is an effective alternate testing system to conventional ELISA where the use of ELISA is not suitable and the result of the HIV testing is needed urgently.

Evaluation Studies as Topic↗

Epidemiology of malaria in pregnancy in central India.

Analysis of three years of data from a malaria clinic operated by the Indian Council of Medical Research (ICMR) in the Government Medical College Hospital in Jabalpur, central India, showed a high malaria prevalence among pregnant women, which was statistically highly significant (P < 0.0001) compared with the situation among nonpregnant women. Cerebral malaria was a common complication of severe Plasmodium falciparum infection, with a high mortality during pregnancy, requiring immediate attention. The study also showed that malaria infection was more frequent in primigravidae, falling progressively with increasing parity. Mean parasite densities were significantly higher in pregnant women compared with nonpregnant women for both P. falciparum (P < 0.001; df = 137) and P. vivax (P < 0.05; df = 72) infection. Pregnant women with falciparum or vivax malaria were significantly more anaemic than noninfected pregnant women or infected nonpregnant women. The average weight of 155 neonates from infected mothers was 350 g less than that of 175 neonates from noninfected mothers. This difference in birth weight was statistically significant for both P. falciparum (P < 0.0001; df = 278) and P. vivax (P < 0.0001; df = 223) infection. Congenital malaria was not recorded. We conclude that pregnant women from this geographical area require systematic intervention owing to their high susceptibility to malaria during pregnancy and the puerperium.

Birth Weight↗

Population dynamics of Anopheles culicifacies and malaria in the tribal area of central India.

A longitudinal study (1993-94) on malaria was conducted in Dungaria, a typical forest fringe tribal village in Mandla district of central India (Madhya Pradesh). Our initial objective was to obtain in-depth baseline data on malaria transmission in the tribal village to elucidate the factors responsible for persistent malaria in the area and thereby to help in formulating an improved malaria control program. Anopheles culicifacies Giles was the predominant vector of malaria, although Anopheles fluviatilis James were recorded in small numbers. The transmission season was from May to November. Analysis of the malaria cases revealed hyperendemic malaria, with Plasmodium falciparum the predominant species. The prevalence of Plasmodium vivax was mainly in the summer and that of P. falciparum in autumn. The study suggested that a number of factors were responsible for the continuation of malaria transmission in the village.

Animals↗