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Biomedical subjects

N Singh

Publications and source records attributed to N Singh.

At least 253 records · Page 14Linked to original sources
PubMed1998

Late onset cytomegalovirus disease in liver transplant recipients: de novo reactivation in recurrent hepatitis C virus hepatitis.

Late onset cytomegalovirus (CMV) disease (occurring more than 1 year post-transplant] was documented in two liver transplant recipients with recurrent hepatitis C virus hepatitis in the absence of factors known to precipitate CMV disease, i.e., primary acquisition of CMV, allograft rejection, augmented immunosuppression, concomitant infections, or blood transfusions. Both patients had CMV enteritis (with CMV adrenalitis in one case]; however, other symptoms and signs of overt CMV infection, i.e., fever, leukopenia, or atypical lymphocytes, were lacking. Hepatitis C virus is an immunomodulatory virus; impaired CMV-specific T-cell responses may have accounted for the predisposition of our patients to unprovoked, late onset CMV disease. Given the high incidence of hepatitis C virus recurrence after liver transplantation, awareness of the occurrence and recognition of the unusual presentation of CMV disease in this setting is both clinically relevant and significant, particularly since CMV is treatable if recognized promptly.

Adult↗
PubMed1998

Outcome of patients with cirrhosis requiring intensive care unit support: prospective assessment of predictors of mortality.

Determinants of outcome and the utility of the Child-Pugh score and the acute physiology and chronic health evaluation (APACHE) II score as predictors of outcome were prospectively assessed in 54 consecutive patients with cirrhosis requiring intensive care unit (ICU) management. Overall mortality in the ICU was 43% (23/54). Child-Pugh scores did not differ between survivors or nonsurvivors (12.8 versus 12.3, P = 0.26), however APACHE II scores (P = 0.007), acute physiology scores (P = 0.006), and Karnofsky scores (P = 0.001) were significant predictors of outcome. By univariate analysis, requirement of mechanical ventilation analysis (P = 0.001), duration of mechanical ventilation (P = 0.001), pulmonary infiltrates (P = 0.0001), infections (P = 0.047), gastrointestinal bleeding (P = 0.005), and serum creatinine >1.5mg/dl (P = 0.0005) were significantly associated with mortality. By logistic regression analysis only pulmonary infiltrates (P = 0.0001) and renal dysfunction (P = 0.041) were independent predictors of mortality. When controlled for the severity of illness (APACHE II scores), the mortality in patients with cirrhosis caused by alcohol was significantly lower than that in patients with liver disease not caused by alcohol (P = 0.01). Our study not only identified predictors of poor outcome in patients with cirrhosis requiring ICU care but also provided data that may have implications for optimal timing for transplantation.

APACHE↗
PubMed1998

Causal prophylactic activity of antihistaminic agents against Plasmodium yoelii nigeriensis infection in Swiss mice.

The causal prophylactic activity of five tricyclic anti-histaminic agents (histamine H1-receptor antagonists) cyproheptadine, ketotifen, loratadine, azatadine and terfenadine was evaluated in an experimental murine malaria model. Sporozoite induced infections with Plasmodium yoelii nigeriensis (N-67), a strain innately resistant to choloroquine, were employed for the efficacy test and pyrimethamine and primaquine were used as standard reference drugs. Treatment with cyproheptadine or ketotifen at 5 mg/kg and terfenadine at 50 mg/kg, orally for 3 days (-1, 0, +1) completely prevented the establishment of patent infection in mice inoculated with 1 x 10(5) sporozoites on day 0. Partial activity was recorded with lower doses of the above agents as well as with azatadine and loratadine at 10 mg/kg as indicated by marginal delay in the development of patent infection after sporozoite challenge. None of these agents showed blood schizontocidal activity at doses found effective in the causal prophylactic test, though initial suppression of parasitaemia was observed with cyproheptadine and ketotifen at higher doses. This study is the first report on efficacy of antihistaminic agents for growth inhibition of pre-erythrocytic stages of any malaria parasite.

Animals↗
PubMed1998

Infective endocarditis in solid organ transplant recipients.

Infective endocarditis, defined as pathologically or clinically definite by the Duke criteria, was observed in 14 transplant recipients at our institutions. In addition, we reviewed 32 previously reported cases in solid organ transplant recipients. The spectrum of organisms causing infective endocarditis was clearly different in transplant recipients than in the general population; 50% of the infections were due to Aspergillus fumigatus or Staphylococcus aureus, but only 4% were due to viridans streptococci. Fungal infections predominated early (accounting for six of 10 cases of endocarditis within 30 days of transplantation), while bacterial infections caused most cases (80%) after this time. In 80% (37) of the 46 cases in transplant recipients, there was no underlying valvular disease. Seventy-four percent (34) of the 46 cases were associated with previous hospital-acquired infection, notably venous access device and wound infections. Three patients with S. aureus endocarditis had had an episode of S. aureus bacteremia > 3 weeks prior to the diagnosis of endocarditis and had received treatment for the initial bacteremia of < 14 days' duration. The overall mortality rate was 57% (26 of 46 patients died), with 58% (15) of the 26 fatal cases not being suspected during life. Endocarditis is an underappreciated sequela of hospital-acquired infection in transplant recipients.

Adult↗
PubMed1998

Mycobacterium tuberculosis infection in solid-organ transplant recipients: impact and implications for management.

Tuberculosis is a serious opportunistic infection in transplant recipients. On the basis of the compilation of published reports in the literature, the incidence of Mycobacterium tuberculosis infection in organ transplant recipients worldwide ranged from 0.35% to 15%. Nonrenal transplantation (P = .004), rejection within 6 months before the onset of tuberculosis (P = .02) and type of primary immunosuppressive regimen (P = .007) were predictors of M. tuberculosis infection occurring within 12 months after transplantation. Thirty-three percent (155) of 476 transplant patients with tuberculosis had disseminated infection; receipt of OKT3 or anti-T cell antibodies (P = .005) was a significant predictor of disseminated tuberculosis. Overall, the mortality rate among 499 patients was 29%; disseminated infection (P = .0003), prior rejection (P = .006), and receipt of OKT3 or anti-T cell antibodies (P = .0013) were significant predictors of mortality in patients with tuberculosis. Clinically significant hepatotoxicity due to isoniazid occurred in 2.5%, 4.5%, and 41% of renal, heart and lung, and liver transplant recipients, respectively. The diagnosis and effective management of tuberculosis after transplantation warrant recognition of the unique epidemiological and clinical characteristics of tuberculosis in transplant recipients.

Adolescent↗
PubMed1998

Fever in liver transplant recipients: changing spectrum of etiologic agents.

Febrile episodes in liver transplants were prospectively evaluated. Fever was due to infections in 78% of the episodes (35 of 45) and due to noninfectious causes in 22% (10 of 45). The predominant sources of fever were bacterial infections (62%; 28 of 45) and viral infections (6%; 7 of 45), whereas rejection accounted for only 4% of the episodes (2 of 45). Forty percent of the infections were unaccompanied by fever; fungal infections were significantly less likely to be associated with fever than were viral or bacterial infections (P = .001). Eighty-six percent (6) of the 7 febrile viral infections were due to viruses other than cytomegalovirus, of which human herpesvirus-6 was the predominant pathogen (71%; 5 of 7). Eighty percent (four) of the five febrile episodes with leukopenia were due to human herpesvirus-6. Episodes of fever were most likely to occur within 12 weeks (58%) or 1 year (29%) after transplantation; 100% of the latter episodes were in patients with recurrent hepatitis due to hepatitis C virus, malignancy, or chronic hemodialysis. In conclusion, cytomegalovirus and rejection were no longer the predominant etiologies of fever in liver transplant recipients, and viruses other than cytomegalovirus (e.g., human herpesvirus-6) are emerging as a significant cause of febrile viral illnesses in these patients.

Adult↗
PubMed1998

Staphylococcus aureus nasal colonization in patients with cirrhosis: prospective assessment of association with infection.

OBJECTIVE: To determine if Staphylococcus aureus colonization of the anterior nares was a risk factor for S aureus infection in patients with cirrhosis and to determine the predictors of S aureus infection in colonized patients. DESIGN: Prospective cohort study. PATIENTS: 84 consecutive patients with cirrhosis admitted to the liver transplant unit of a university-affiliated Veterans' Affairs Medical Center. RESULTS: Overall, 39 (46%) of the 84 patients were nasal carriers of S aureus, of which 24 (29%) were methicillin-resistant Staphylococcus aureus (MRSA) and 15 (18%) were methicillin-sensitive Staphylococcus aureus (MSSA). Only MRSA, but never MSSA, carriage was acquired in the hospital; all 15 of the MSSA versus 14 (58%) of the 24 MRSA carriers were nasal carriers on first (admission) culture (P=.001). Of the 10 (42%) of 24 MRSA carriers who were not colonized on admission, 3 became MRSA carriers within 1 month, and 7 acquired MRSA carriage more than a month later. Higher Child-Pugh score was independently associated with MRSA carriage (odds ratio [OR], 1.54; 95% confidence interval [CI95], 1.1-2.3). S aureus nasal carriers (9 [23%] of 39) were significantly more likely to develop S aureus infections than noncarriers (2 [4%] of 45; P=.02). Central venous catheter use was associated independently with S aureus infections in the carriers (OR, 4.1; CI95 2.8-6.1). Mortality was significantly higher in carriers who developed S aureus infections as compared to those who did not (57% vs 13%; P=.022); S aureus infection was an independent predictor of mortality in the carriers (OR, 8.7; CI95, 1.2-63.8). CONCLUSIONS: Colonization of the anterior nares was a significant predictor of S aureus infection in patients with cirrhosis.

Adult↗
PubMed1998

Evolution of transcriptional regulatory elements within the promoter of a mammalian gene.

Transcription of the murine D7Rp2e gene is highly variable among species of the genus Mus, indicating that extensive modifications in the gene's regulatory elements have occurred during evolution. Since promoter regions are well known to harbor cis-acting information that controls gene transcription, we compared the sequence and function of the D7Rp2e promoter in several Mus species, with the goal of understanding the molecular mechanisms underlying the interspecies variations in expression. Three overlapping binding sites for nuclear factors (sites A, B, and C in proximal to distal order) were identified about 300 bp upstream of the transcriptional start site. The sequences of these sites differ between the species Mus domesticus and M. pahari, which exhibit distinct D7Rp2e expression phenotypes. Site A binds a factor called RPBF-I; sites B and C bind a distinct factor that is termed RPBF-II and is likely a member of the NF-I family of transcription factors. DNase I footprinting experiments with the M. domesticus promoter show that binding of RPBF-II at site B is very strong, while binding of RPBF-I and RPBF-II at sites A and C, respectively, is weak; in contrast, with the M. pahari promoter, factor binding at sites A and C is strong, while that at site B is weak. These differences in patterns of binding-site occupancy derive from changes in the affinities of individual sites for their cognate nuclear factors. Transient transfection experiments indicate that the M. pahari binding pattern is capable of repressing transcription of a linked reporter. Such repression may contribute to the differences in D7Rp2e expression between the two species. We suggest that the species-specific footprinting patterns represent the existence of a dynamic equilibrium between two states of nuclear factor binding, the nature of which can be modified during evolution to result in new patterns of gene transcription.

Animals↗
PubMed1998

Infections in solid organ transplant recipients.

Delineation of the pathogenic potential and assessment of the efficacy of newer therapeutic modalities for a number of viruses have been among the more notable developments in solid organ transplant infections within the past year. Infection caused by the novel herpesvirus, human herpesvirus-6, was proposed to be a significant cause of fever of unknown origin and a predictor of subsequent cytomegalovirus infection. Interleukin-2-primed isologous T lymphocytes led to the complete regression of Epstein-Barr virus-positive post-transplant lymphoproliferative disorder. Although interferon-alpha alone was shown to be largely ineffective as prophylaxis and treatment for hepatitis C virus hepatitis, the combination of interferon-alpha and ribavirin appeared promising. Documentation within the past year, however, of lamivudine and famciclovir resistance in hepatitis B virus, ganciclovir resistance in cytomegalovirus, and azole resistance in Candida, is a sobering reminder that antimicrobial prophylaxis must be utilized rationally and selectively.

Journal Article↗
PubMed1998

Pulmonary nodules in liver transplant recipients.

Pulmonary nodules present a diagnostic dilemma in liver transplant recipients because of the broad differential diagnosis involved. Eleven of 155 (7.1%) liver transplant recipients at the Veterans Affairs Medical Center, Pittsburgh, developed pulmonary nodules. The underlying etiology included aspergillosis (3 cases), cryptococcosis (2), metastatic hepatocellular carcinoma (1), posttransplant lymphoproliferative disorder (1), Staphylococcus aureus (1), squamous cell carcinoma (1), adenocarcinoma of unknown primary site (1), and undifferentiated carcinoma (1). A review of the literature revealed 22 other liver transplant recipients with pulmonary nodules. There appears to be a definite relationship between time since transplantation and etiology of the nodule. Aspergillosis and bacterial infections appear early (within the first month), whereas nocardiosis, coccidiomycosis, tuberculosis, and cryptococcosis occur from 3 to 24 months posttransplantation. Metastatic hepatocellular carcinoma is a relatively common cause of pulmonary nodule and appears from 2 months to 2 years posttransplantation. Detection of skin lesions (indicating nocardiosis or cryptococcosis) and positive serologic tests may further narrow the diagnosis. However, radiographic appearances of nodules of differing etiology are relatively nonspecific, necessitating biopsy in virtually all cases.

Adult↗
PubMed1998

Is the heredity of reticulate acro pigmentation of Kitamura always autosomal dominant?

Reticulate acropigmentation of Kitamura (RAK) in three patients and their families is described. In one family, 2 women and 2 men were affected out of 9 individuals. In the other family, 6 women had lesions of reticulate acropigmentation out of total of 27 over three generations. In the third family, one man was affected. All of the cases had palmar pits; onset of lesions was after puberty in all the cases. The apparently different hereditary patterns in these three families are striking, and autosomal dominant inheritance appears unlikely in every case.

Acrodermatitis↗
PubMed1998

Nodular post-kala-azar dermal leishmaniasis: a distinct histopathological entity.

Post-kala-azar dermal leishmaniasis (PKDL) is an infrequently occurring sequel to treated visceral leishmaniasis. Diagnosis, particularly in non-endemic areas, is difficult because the clinical appearances may be subtle and simulate lepromatous leprosy. The histopathology of the condition has been a neglected subject. Nodular lesions constitute one of the large variety of lesions that can be seen in PKDL. This paper describes the histopathology of such lesions in 26 patients seen over a period of approximately 8 years in a non-endemic setting. All the biopsies had strikingly similar light microscopic features with characteristic findings: a dense lymphohistiocytic infiltrate beneath an atrophic epidermis, pronounced follicular plugging, vascular hyalinization and collagen changes and negative Fite stain. These allow a definite diagnosis of PKDL even in the absence of demonstrable Leishman-Donovan (L-D) bodies.

Biopsy↗
PubMed1998

Possible mechanism of alprazolam-induced amnesia in mice.

Alprazolam produced anterograde as well as retrograde amnesia in mice assessed using elevated plus-maze. Flumazenil (10 mg/kg i.p.) attenuated anterograde and retrograde amnesia produced by alprazolam. It is proposed that anterograde amnesia produced by alprazolam may be mediated through the activation of benzodiazepine receptors. Retrograde amnesia of alprazolam may be mediated through the blockade of PAF receptors. Moreover, flumazenil facilitates learning and memory perhaps by modulating the release of PAF and consequently attenuated alprazolam and BN-50730-(PAF receptor antagonist)-induced retrograde amnesia.

Alprazolam↗