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Biomedical subjects

N Singh

Publications and source records attributed to N Singh.

At least 325 records · Page 18Linked to original sources

Bloodstream infections in liver transplant recipients receiving tacrolimus.

The microbial origin, timing, risk factors, and outcome of bloodstream infections (bacteremia and fungemia) were prospectively analyzed in 130 consecutive liver transplant recipients receiving tacrolimus-based immunosuppression; median followup was 3 yr. 22% (29/130) of the patients developed 36 episodes of bloodstream infections (0.28 episodes/patient). Bloodstream infections accounted for 36% (36/100) of all major infections. 81% (29/36) of bloodstream infections were due to bacteremia and 19% (7/36) due to fungemia (candidemia 14% and cryptococcemia 5%). Intravascular catheters were the most frequent source and methicillin-resistant Staphylococcus aureus was the most frequent pathogen causing bloodstream infections. 70% of the catheter related and all bacteremias due to intra-abdominal infections occurred < or = 90 d, whereas 75% of the bacteremias due to biliary source occurred > 90 d after transplantation. Length of initial post-transplant intensive care unit stay (p = 0.014) and readmission to the intensive care unit (p = 0.003) were independently significant predictors of bloodstream infections. 40% of the candidemias occurred within 30 d of transplantation and were of unknown portal, whereas the portal in all candidemias occurring > 30 d post-transplant was known (catheter, hepatic abscess, urinary tract). Mortality in patients with bloodstream infections was 52% (15/29) vs. 9% (9/101) in patients without bloodstream infections (p = 0.0001). In conclusion, intravascular catheters (and not intra-abdominal infections) have emerged as the most common source of bloodstream infections, and gram-positive cocci (S. aureus) as the predominant pathogens in bloodstream infections after liver transplantation.

Abdomen↗

Efficacy of light-traps in sampling malaria vectors in different ecological zones in central India.

This preliminary field study was designed chiefly to test the efficiency of the light-trap as a tool for sampling malaria vectors, in tribal villages located in different ecological settings in comparison with indoor resting collections as an alternative method. Anopheles culicifacies, a known malaria vector, was the most prevalent species in the study villages and more than 80% of trap catches were obtained before midnight with peak activity during dusk. Reproductive status of trapped specimens revealed proportional representations of unfed, freshly fed, and gravid females. Another vector, An. fluviatilis was found in small numbers by both the methods. Thus the trap could give a reliable and unbiased sample of vector population. Seven species were abundant in the light-trap catches while only four in the indoor resting collections indicates the usefulness of the light-trap for sampling exophilic species. The study revealed that light-traps did not have any bias in favor of any particular species. The method may be useful for assessing the night time densities of different species or the fluctuation of a species at different dates and village to village variations. Light-traps could be used for sampling both endophilic and exophilic anophelines.

Animals↗

Vulnerability to psychologic distress and depression in patients with end-stage liver disease due to hepatitis C virus.

Psychosocial sequelae and quality of life impairment in patients with end-stage liver disease due to hepatitis C virus (HCV) are not known. Quality of life, psychological distress (Profile of Mood State scale), depression (Beck Depression Inventory), and coping (Ways of Coping scale) were prospectively assessed in 82 liver transplant candidates; comparisons were made between patients with HCV hepatitis versus patients with other liver diseases. Patients with HCV were significantly younger than all other patients (p = 0.002). Total mood disturbance (p = 0.038), tension and anxiety (0.047), confusion and bewilderment (p = 0.035) and depression and dejection (p = 0.035), as assessed by Profile of Mood States Scale were significantly higher in patients with HCV than other patients. Patients with HCV were significantly more depressed as assessed by Beck Inventory scores (p = 0.014). Karnofsky performance scores, Child-Pugh score, and liver function tests were not significantly different for patients with HCV vs. all other patients. However, somatic manifestations of the illness (e.g. pain) were greater in patients with HCV and may have contributed towards greater depression in these patients. Our findings warrant replication in other studies, since depression is a modifiable and treatable disorder.

Adaptation, Psychological↗

FNAC and transabdominal ultrasonography in the diagnosis of prostatomegaly.

Transrectal fine needle aspiration cytology (FNAC) was performed in 100 cases of prostatomegaly detected by digital rectal examination (DRE). The cytologic findings were compared with histolgic findings of material obtained by transurethral resection of prostate (TURP) in 84 of the cases. In addition, pre-prostatectomy transabdominal ultrasonography was done in 55 of the cases and the findings were compared with cytologic and histologic diagnoses. The accuracy of diagnosis by FNAC for benign lesions and carcinoma of prostate was 98.33% and 81.81% respectively. The accuracy of transabdominal ultrasonography for benign lesions was 91.66% but that for carcinoma was only 38.46%. The technique of transrectal FNAC was found to be simple quick, economical and easy to repeat with high accuracy and was suitable for outpatients.

Adenocarcinoma↗

Intra-abdominal lymphangioma--clinicopathological profile of a rare lesion.

Lymphangioma occurring in an intra-abdominal location is reported to be extremely rare. A series of 5 cases is presented and the differential diagnoses and diagnostic features discussed. None of the cases were diagnosed as lymphangioma clinically. It is suggested that their true incidence may be unknown due to both silent clinical course as well as lack of awareness of clinical and morphological features.

Abdominal Neoplasms↗

Effects of BN-50730 (PAF receptor antagonist) and physostigmine (AChE inhibitor) on learning and memory in mice.

The present study was designed to investigate the effect of BN-50730, a PAF receptor antagonist, on learning and memory in mice using elevated plus-maze and to delineate the role of acetylcholine in modulating the effect of PAF receptor antagonist on learning and memory. BN-50730 administered immediately after plus-maze training on day 1 induced retrograde amnesia as indicated by a dose-dependent increase in transfer latency (TL) measured on day 2 whereas no such increase in TL was noted when BN-50730 (2.5 mg/kg, i.p.) was administered prior to plus-maze training. Physostigmine (0.5 mg/kg; 1.0 mg/kg, i.p.) administered 30 min prior to plus-maze training attenuated BN-50730-induced increase in TL measured on day 2. These results suggest that BN-50730, a PAF receptor antagonist, produced retrograde amnesia and physostigmine attenuated BN-50730-induced amnesia possibly through increased concentration of cerebral acetylcholine and a consequent increase in PAF release.

Acetylcholine↗

Observations on mosquito breeding in rice fields in two ecological terrains of district Jabalpur, Madhya Pradesh.

Studies on ecological succession of anophelines and the malaria vectors were carried out in rice fields located in two ecologically different terrains, i.e. plains and forested hills in Jabalpur district during monsoon (July-October 1995). Nine and fifteen species of anophelines were found breeding in the rice fields of plain and forested hill villages respectively. Anopheles culicifacies and An. subpictus were dominant species in both the areas. The percentage emergence of adults of An. annularis, An. nigerrimus and An. pallidus was higher in plain villages while the percentage of An. theobaldi, An. fluviatilis and An. jeyporiensis was higher in forested hill villages. Among malaria vectors, three species were found breeding in rice fields of hilly terrain, i.e. An. culicifacies, An. fluviatilis and An. stephensi whereas in rice fields of plains An. culicifacies and An. fluviatilis were recorded.

Animals↗

The existence of a hexameric intermediate with molten-globule-like properties in the thermal denaturation of bovine-liver glutamate dehydrogenase.

We have studied the thermal denaturation of hexameric beef-liver glutamate dehydrogenase by itself and in the presence of ADP and guanidine-HCl by a variety of techniques. In differential scanning calorimetry studies, the observed melting temperature and total enthalpy of denaturation show no dependence on protein concentration, but do show significant dependence on the scan rate. This suggests that the overall denaturation process is irreversible and kinetically controlled. Isothermal unfolding kinetics from spectrophotometry confirm this result. The size of the protein, as shown by quasi-elastic light scattering measurements, does not change during the denaturation process. We interpret these results in terms of the following model: N6 reversible N'6-->6U(-->F) where N6 and N'6 are, respectively, the native hexamer and a hexameric, highly folded high-enthalpy species, U is the unfolded monomer and F is some final aggregated state. The kinetic intermediate, N'6, possesses the properties of one definition of a molten globule, having a very high enthalpy and a hexameric compact structured form. This "molten globule" is an obligatory intermediate in the unfolding pathway of the protein. The stabilization of the protein by ADP is due to the modulation of the high-enthalpy two-state predenaturational E reversible E' transition, resulting in the lowering of the energy of the native state of the protein.

Adenosine Diphosphate↗

Calcium ionophore A 23187 induces apoptotic cell death in rat thymocytes.

Apoptotic cell death was induced in rat thymocytes on exposure to calcium ionophore A 23187 (100 micron(s)) for 24 h as observed from morphological changes and DNA fragmentation into oligonucleosomal ladder. The cell death was independent of de novo syntheses of protein. However, the involvement of c-Myc, c-Jun, poly ADPR polymerase and antioxidant enzymes CuZn SOD and catalase was observed.

Animals↗

Human herpesvirus-6 in transplantation: an emerging pathogen.

BACKGROUND: Human herpesvirus-6 can be an opportunistic pathogen in transplant recipients. PURPOSE: To summarize the epidemiologic and clinical aspects of human herpesvirus-6 infection, the immunologic basis of the pathogenicity of human herpesvirus-6, and the management of human herpesvirus-6 infection in transplant recipients. DATA SOURCES: English-language articles identified through a MEDLINE search from 1986 (when human herpesvirus-6 was discovered) to the present, bibliographies of identified articles, and recognized texts. STUDY SELECTION: Reports on human herpesvirus-6 infections in bone marrow transplant recipients and in solid organ transplant recipients. DATA EXTRACTION: Data on the virology, detection, epidemiology, clinical features, and treatment of human herpesvirus-6 infection were manually abstracted from the indicated sources and summarized. Data quality and validity were independently assessed by both authors. DATA SYNTHESIS: Human herpesvirus-6 infection occurred in 38% to 60% of bone marrow transplant recipients and 31% to 55% of solid organ transplant recipients, usually 2 to 4 weeks after transplantation. Human herpesvirus-6 has two variants, designated variant A and variant B; transplant recipients were infected almost exclusively with variant B. Bone marrow suppression, interstitial pneumonitis, and encephalitis were the most commonly reported types of clinical disease caused by human herpesvirus-6. The marrow-suppressive effect of human herpesvirus-6 ranged from transient or self-limited bone marrow suppression to chronic or fatal aplastic anemia; bone marrow suppression was thought to be partially cytokine-mediated. Because it can depress cell-mediated immunity, human herpesvirus-6 may facilitate superinfection by other pathogens. Human herpesvirus-6 resembles cytomegalovirus in its antiviral susceptibilities: It is resistant to acyclovir but susceptible to ganciclovir and foscarnet. Prophylaxis of human herpesvirus-6 infection is feasible in transplant recipients, but this issue must be studied further. CONCLUSION: Human herpesvirus-6 can be a pathogen in transplant recipients. Prompt recognition of disease associated with human herpesvirus-6 is important because this virus is susceptible to currently available antiviral agents. Future research should focus on delineating the complete clinical spectrum, immunologic sequelae, and efficacy of prophylactic strategies for human herpesvirus-6 infection in transplant recipients.

Antiviral Agents↗

A novel class of cell surface glycolipids of mammalian cells. Free glycosyl phosphatidylinositols.

Glycosyl phosphatidylinositol (GPI) lipids function as anchors of membrane proteins, and free GPI units serve as intermediates along the path of GPI-anchor biosynthesis. By using in vivo cell surface biotinylation, we show that free GPIs: 1) can exit the rough endoplasmic reticulum and are present on the surface of a murine EL-4 T-lymphoma and a human carcinoma cell (HeLa), 2) arrive at the cell surface in a time and temperature-dependent fashion, and 3) are built on a base-labile glycerol backbone, unlike GPI anchors of surface proteins of the same cells. The free GPIs described in this study may serve as a source of hormone-sensitive phosphoinositol glycans. The absence of free GPIs from the cell surface may also account for the growth advantage of blood cells in paroxysmal nocturnal hemoglobinuria.

Animals↗

Heart rate variability assessment early after acute myocardial infarction. Pathophysiological and prognostic correlates. GUSTO ECG Substudy Investigators. Global Utilization of Streptokinase and TPA for Occluded Arteries.

BACKGROUND: Diminished heart rate variability is associated with less favorable prognosis after myocardial infarction. However, the prognostic value of early (first 48 hours) measurement and the influence of thrombolytic strategies, myocardial infarction location, left ventricular function, ST-segment shift, and infarct-related artery patency on heart rate variability have not been examined comprehensively. METHODS AND RESULTS: Heart rate variability and ST-segment analysis of 48-hour Holter tapes were performed with the use of a commercial system in 204 patients who were part of an ST-monitoring substudy of the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-I) trial. Both time-domain measures (SD of the average normal RR interval for all 5-minute segments of a 24-hour ECG recording [SDANN] and percent difference between adjacent normal RR intervals > 50 ms computed over the entire 24-hour ECG recording [pNN50]) and frequency-domain measures (low frequency [LF], high frequency [HF], and LF/HF ratio) were assessed on days 1 and 2 after acute myocardial infarction. Coronary angiography performed within the first 24 hours was also available in 75% of the patients. All heart rate variability measures decreased between day 1 and day 2 (P = .001) except the LF/HF ratio. There was no difference in heart rate variability among groups assigned to one of four different thrombolytic treatment strategies (streptokinase/subcutaneous heparin, streptokinase/intravenous heparin, accelerated tissue plasminogen activator, and combination streptokinase/tissue plasminogen activator). Heart rate variability measures were lower in anterior versus nonanterior infarcts (SDANN, 53 +/- 21 versus 63 +/- 24 ms; P < .005) and increased with TIMI grade 3 flow (LF, 5.3 +/- 1.0 versus 4.8 +/- 1.2 ms2; P < .01) and better ejection fraction (r = .2, P < .03). An inverse correlation between the duration of ST shift and frequency domain measures was observed (LF, r = -.2, P < .009; HF, r = -2, P < .03). Lower LF/HF ratio by 24 hours after myocardial infarction was seen in those who ultimately died at 30 days (1.0 +/- 0.2 versus 1.3 +/- 0.2, P < .001) or at 1 year (1.17 +/- 0.14 versus 1.26 +/- 0.19, P = .05). CONCLUSIONS: Changes in heart rate variability occurred early after thrombolysis and may be of prognostic value. Heart rate variability measures were improved in patients with better ejection fraction and greater angiographic patency. This suggests a possible mechanism for the enhanced survival observed with TIMI grade 3 flow in the GUSTO angiographic substudy. These data indicate that early heart rate variability assessment after myocardial infarction may be useful in noninvasive risk stratification.

Bradycardia↗

Pulmonary infections in liver transplant recipients receiving tacrolimus. Changing pattern of microbial etiologies.

Pulmonary infections are a significant cause of morbidity after liver transplantation; Gram-negative bacilli, cytomegalovirus, and Pneumocystis carinii were the usual pulmonary pathogens in the earlier studies in liver transplant recipients receiving cyclosporine. We prospectively assessed the impact of pulmonary infection in 101 consecutive liver transplant recipients receiving the new immunosuppressive agent tacrolimus (FK506). Fifteen percent (15/101) of the patients had 19 episodes of pneumonia; 58% (11/19) of the pneumonias were bacterial, 37% (7/19) were fungal, and 5% (1/19) were protozoal (Toxoplasma gondii). Twenty-seven percent of the bacterial pneumonias were due to Legionella. None of the patients had cytomegalovirus or P carinii pneumonia. Seven percent (7/10) of the study patients had fungal pneumonitis; 4% had invasive aspergillosis and 3% had cryptococcosis. Mortality was significantly higher (53%, 8/15) for patients with pneumonia than for patients without pneumonia (10%, 9/86, P = 0.0004). Only fungal pneumonias were the direct cause of death; 63% (5/8) of the deaths were in patients with fungal pneumonitis. Our data suggest a changing pattern of microbial etiologies of pneumonitis in the era of modern immunosuppressive agents. We show that P carinii pneumonia and cytomegalovirus can be effectively curtailed with appropriate prophylaxis. Fungal infections, on the contrary, not only constituted a major proportion of the pneumonia, but also carried the highest pneumonia-associated mortality. Legionella infections can be overlooked unless specialized laboratory methodology (cultured on selective media, urinary antigen) are applied routinely on all cases of pneumonia. We recommend routine culture on the water supply for Legionella in all transplant centers.

Adult↗

Increased infections in liver transplant recipients with recurrent hepatitis C virus hepatitis.

Infectious complications in patients with recurrent hepatitis C virus (HCV) hepatitis after liver transplantation were prospectively assessed and compared with those of all other liver transplant recipients without HCV hepatitis operated on during the same period. Major infections occurred in 64% (14/22) of the patients with recurrent HCV hepatitis versus 38% (30/78) of all other patients (P = 0.04). Patients with recurrent HCV hepatitis had significantly more episodes of major infections (mean 1.45 episodes/patient vs. 0.51 episodes/patients, P = .003) and were more likely to have recurrent episodes of major infections (45%, 10/22, vs. 10%, 8/78, P = 0.005) than all other patients, respectively. The incidence of major bacterial infections was not higher in patients with recurrent HCV hepatitis (41% vs. 28%, P = NS); however, incidence of fungal infections was higher (18% vs. 6%, P = 0.10) and incidence of cytomegalovirus disease was significantly higher (32% vs. 9%, P = 0.012) in patients with recurrent HCV hepatitis as compared with all other patients. Late infections, i.e., those occurring > 6 months after transplantation, were significantly higher in patients with recurrent HCV (27% vs. 6%, P = 0.011). Rejection episodes occurring within 6 months after transplantation were higher in patients with recurrent HCV hepatitis (P = 0.09); however, the intensity of immunosuppression as measured by corticosteroid boluses and cycles was not significantly different in these patients when compared with all other patients. Aminotransferase levels were significantly higher in patients with HCV recurrence than in other patients. We conclude that recurrent HCV hepatitis after liver transplantation is associated with a high incidence of infections due to pathogens associated with depressed cell-mediated immunity. Future studies should assess the exact nature of the suppressive effect on host defense in recurrent HCV hepatitis.

Adult↗

A high incidence of native portal vein thrombosis in veterans undergoing liver transplantation.

The incidence of native portal vein thrombosis (PVT) in liver transplant recipients has been reported to range from 2.1 to 13.8%. We have identified an inordinately high incidence of PVT in a consecutive series of U.S. veterans receiving liver transplants. Between October 1989 and February 1994, 88 consecutive U.S. veterans received 99 orthotopic liver transplants under primary Tacrolimus (Prograf, formerly FK506) based immunosuppression. A number of clinical features were examined in an effort to identify risk factors for PVT and outcome was compared to patients without PVT. Native PVT was present in 23/88 (26%) patients. All of these patients were male U.S. veterans with a mean age of 47 years. When compared to the 65 patients without PVT, we found no significant difference with respect to underlying liver disease, age, Childs-Pugh score (mean = 12), UNOS status as defined prior to April 1995 (95% UNOS 3 or 4), previous abdominal surgery, or liver volume. Median blood loss for patients with PVT (21 units of packed red blood cells) was greater than for those without PVT (14 units, P = 0.04). Portal thrombectomy was performed in 11 patients, 11 patients required mesoportal jump grafts, and 1 patient had an interposition graft. Standard veno-venous bypass was used in 10 patients with single bypass utilized for the remainder. Actuarial patient survival for all patients at 1, 2, and 4 years was 88, 85, and 79%, respectively. There was no significant difference in patients with or without PVT. Patients with PVT had poorer graft survival than patients without PVT (86% vs 65%, 1 year; 81% vs 65%, 2 years; 81% vs 61%, 4 years; P = 0.03); however, this was not related to technical problems with the portal venous inflow. PVT occurred in 26% of U.S. veterans undergoing liver transplantation. These patients had significantly higher operative blood loss and poorer graft survival. The high incidence of postnecrotic cirrhosis in a predominantly male group of patients with advanced disease, as is evident by the high mean Childs-Pugh score and UNOS status, perhaps accounts for our observations.

Female↗

Determinants of nontraditional therapy use in patients with HIV infection. A prospective study.

BACKGROUND: The popularity and use of nontraditional therapies among patients with human immunodeficiency virus (HIV) infection has grown enormously. DESIGN: A prospective, longitudinal cohort study of 56 patients aged 23 through 68 years with HIV infection followed up at the HIV clinic at a university-affiliated Veterans Affairs Medical Center. OBJECTIVE: To assess the demographic and psychologic characteristics of patients who seek nontraditional remedies, and their impact on disease progression and mortality from HIV. METHODS: A standardized, self-administered questionnaire to assess the incidence and type of nontraditional therapies used by patients with HIV. Data on demographics, medical status, physical functioning (Karnofsky performance score), CD4 lymphocyte counts, depression (Beck Depression Inventory), coping (inventory of coping with illness scale), psychological and/or emotional stress (Profile of Mood States scores), and compliance with prescribed therapy were prospectively assessed on all patients at baseline and every 6 months. RESULTS: Thirty percent of patients reported using nontraditional therapies. Nontraditional therapy users were significantly older than patients who did not use such therapies (44 vs 38 years, P = .03); with 94% of patients who used nontraditional therapy being older than 35 years compared with 56% of conventional therapy users (P = .005). Alternative therapy use did not correlate with race, education, HIV-risk group affiliation, duration of HIV seropositivity, stage of HIV disease, CD4 cell count, or Karnofsky performance scores. Nontraditional therapy users reported greater community-based acquired immunodeficiency syndrome group support (P = .06), greater perceived social support (P = .08), and significantly higher recreational or "street drugs" use (P = .02). Depression, adaptive coping, and emotional stress were not different between nontraditional and conventional therapy users; however, nontraditional therapy users were significantly more assertive (P = .04). On follow-up, CD4 cell count, HIV disease progression, physical functioning, or mortality were similar between the two groups. CONCLUSIONS: Recourse to nontraditional therapy is common among patients with HIV. Because of the possibility of untoward effects and potential adverse drug interactions associated with nontraditional therapy, HIV care givers should be aware of its use in their patients and take a history of nontraditional therapy first. Patients who choose nontraditional remedies do so not because they are depressed or emotionally disturbed, but rather because they seek greater control of the outcome of their disease. However, no beneficial effect on disease progression, CD4 cell count, or mortality was observed in these patients when compared with patients receiving only conventional medical therapy.

Adaptation, Psychological↗

Positive correlation between apoptotic and proliferative indices in gastrointestinal lymphomas of mucosa-associated lymphoid tissue (MALT).

To understand the role of deregulation of apoptosis in the pathogenesis of gastrointestinal MALT lymphoma, apoptosis has been quantitatively studied in paraffin sections from 40 cases (19 low grade, 21 high grade). The extent of apoptosis was correlated with histological grade, proliferative activity as measured by immunostaining of Ki67 proliferation antigen, and the expression of bcl-2 and p53 oncoproteins, which are known to participate in the regulation of apoptosis. Both apoptotic and proliferative indices were significantly (P < 0.00001) higher in high-grade than in low-grade tumours. Overall, apoptotic indices were negatively correlated with bcl-2 expression, particularly in low-grade tumours in which both strong bcl-2 expression and low levels of apoptosis were observed. Thus, the slow expansion of low-grade MALT lymphoma may partly result from a prolonged life-span of tumour cells, due to bcl-2-mediated blockage of apoptosis. No difference in apoptotic indices was found between p53-positive and p53-negative cases. Furthermore, correlation analysis revealed a significantly positive association between apoptotic and proliferative indices. This supports the current belief that the mechanisms controlling apoptosis and proliferation are both activated during the cell cycle and whether a cell enters the proliferation cycle or the apoptotic process depends on survival factors.

Apoptosis↗