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Biomedical subjects

N Singh

Publications and source records attributed to N Singh.

At least 343 records · Page 19Linked to original sources

Toxoplasma gondii pneumonitis in a liver transplant recipient: implications for diagnosis.

Toxoplasma gondii pneumonia developed 27 days after retransplantation for chronic rejection in a liver transplant recipient receiving tacrolimus as primary immunosuppression. Trimethoprim-sulfamethoxazole had been discontinued (due to cytopenia) before the onset of T gondii pneumonia. T gondii was isolated from bronchoalveolar lavage fluid by growth in fibroblast cell culture routinely used for the isolation of viruses and detected in lung on autopsy. Tissue culture used for the detection of viruses can also be diagnostically useful for the detection of T gondii.

Adult↗

Hemolytic uremic syndrome in solid-organ transplant recipients.

Post-transplant hemolytic uremic syndrome characterized by microangiopathic hemolysis, thrombocytopenia, and renal failure is an infrequent but potentially serious complication in organ transplant recipients. Hemolytic uremic syndrome developed in 2% (2/100) of our consecutive liver transplants. We report our patients and review a total of 91 cases of hemolytic uremic syndrome in adult solid organ transplant recipients reported in the literature. Ninety percent were observed in renal transplant recipients, 8% in liver, and 1% each in lung and heart transplant recipients. Eighty percent and 96% of cases occurred within 90 days and 1 year, respectively, post-transplantation. In renal transplant recipients, 23% of cases were due to post-transplant recurrence of hemolytic uremic syndrome. In 50% of renal transplant recipients and in all nonrenal solid-organ transplant recipients, hemolytic uremic syndrome was attributed to cyclosporin or tacrolimus therapy. Notably, infections were not a significant precipitating factor for post-transplant hemolytic uremic syndrome. Graft loss attributable to hemolytic uremic syndrome occurred in 43% of renal transplant recipients while renal transplantation and hemodialysis were required in the lung and heart transplant recipients due to hemolytic uremic syndrome induced renal failure. The overall mortality was 13% (12/91). Physicians caring for transplant recipients need to be aware of this potentially severe graft and life-threatening disorder since prompt recognition and removal of identifiable risk factors is critical in the management of post-transplant hemolytic uremic syndrome.

Adult↗

A randomized, prospective trial of stapled lung reduction versus laser bullectomy for diffuse emphysema.

Two procedures (laser bullectomy and lung reduction surgery with staples) are currently available for the surgical treatment of patients with diffuse emphysema. We compared the efficacy of these two surgical approaches in 72 patients, aged 67 +/- 7 years (mean +/- standard deviation), who had diffuse emphysema scored as severe on computed tomography and severe fixed expiratory airflow obstruction. The patients were prospectively randomized to undergo either neodymium:yttrium aluminum garnet contact laser surgery (n = 33) or stapled lung reduction surgery (n = 39) by unilateral thoracoscopy. The operative mortalities were 0% and 2.5%, respectively. No significant differences were noted between the groups (p < 0.05) with respect to operating time, hospital days, or air leakage for more than 7 days. However, a delayed pneumothorax developed in six patients (18%) who had laser treatment (p = 0.005). The operations eliminated dependency on supplemental oxygen in 52% of the laser group and 87.5% of the stapled lung reduction group (p = 0.02). The mean postoperative improvement in the forced expiratory volume in 1 second at 6 months was significantly greater for the patients undergoing the staple technique (32.9% vs 13.4%, p = 0.01) than for the laser treatment group.

Aged↗

Recurrent hepatitis C virus hepatitis in liver transplant recipients receiving tacrolimus: association with rejection and increased immunosuppression after transplantation.

BACKGROUND: Recurrent hepatitis C virus is associated with significant morbidity and mortality after liver transplantation. However, the risk factors for clinical recurrence including the role of rejection and immunosuppression have not been defined in patients receiving tacrolimus (FK506) as primary immunosuppression. METHODS: Sixty-six consecutive adult liver transplant recipients receiving tacrolimus as primary immunosuppression were monitored; 31 of 66 underwent transplantation for end-stage liver disease caused by hepatitis C virus. Median follow-up for the patients in the study was 3 1/2 years. Recurrent hepatitis C virus hepatitis determined on histopathologic evaluation developed in 58% (18 of 31). A number of clinical variables including rejection and intensity of immunosuppression were assessed for patients with and without recurrence. RESULTS: Rejection episodes preceding recurrence were documented in 72% (13 of 18) of patients with recurrence compared with 23% (3 of 13) in those without recurrence (p=0.007). A total of 33% (5 of 15) of patients with no rejection experienced recurrence versus 83% (5 of 6) with one episode of rejection (p=0.06) and 80% (8 of 10) with more than one episode of rejection (p=0.04). The mean number of steroid boluses for the treatment of rejection was higher for patients with recurrence (2.3 versus 0.77, p=0.01). Overall immunosuppression (as measured by steroids boluses, recycles, OKT3, and azathioprine) was significantly more intense for patients with recurrence (p=0.013). CONCLUSIONS: Greater rejection concurrent with increased immunosuppression was associated with a higher recurrence of hepatitis C in liver transplant recipients.

Adult↗

Oral complications of cancer therapies: prevention and management.

There is no doubt that, when the oncology team includes a dentist, the risks of development of serious complications such as osteoradionecrosis are significantly reduced for the cancer patient [15,157,158]. Ideally, all patients should be rendered dentally fit before the commencement of cancer therapy. Those receiving radiotherapy should then be seen weekly by the dentist during the course of radiotherapy and approximately every 1-2 weeks during the intensive phases of treatment, if receiving chemotherapy or surgery. All patients should be carefully followed up after cancer therapy in order to minimize orofacial complications and be in a position to intervene at an early stage, when therapy is likely to be easier and more rapidly effective.

Dental Care↗

Low grade gastric B-cell lymphoma of mucosa associated lymphoid tissue in immunocompromised patients.

An increased incidence of non-Hodgkin's lymphoma is seen in patients with immunodeficiency from any cause. The majority of these are high grade B-cell lymphoma and most are associated with the Epstein-Barr virus (EBV). In post-transplant lymphoma/lymphoproliferative disorders the tumour may regress following reduction of immuno-suppression but in AIDS the lymphomas show a characteristic aggressive course and poor prognosis. We describe low grade B-cell gastric lymphoma of mucosa associated lymphoid tissue (MALT) in three immunocompromised patients (two post-transplant, one HIV positive). In each case, the tumour showed classical morphological features of gastric MALT lymphoma and was not associated with EBV. Helicobacter pylori was identified in each case. Clinical follow-up suggests that the behaviour in these tumours is similar to that seen in MALT lymphomas in immunocompetent patients and not typical of the lymphomas usually associated with immunosuppression. Although the finding of MALT lymphoma in immunosuppressed patients might be coincidental, the association of some MALT lymphomas with autoimmune disease suggests that dysregulation of the immune system might play a role in the pathogenesis of these tumours.

Aged↗

Analysis of T-cell hybridomas with an unusual MHC class II-dependent ligand specificity.

We have characterized two unusual T-cell hybridomas, 1E3 and 3B8, from H-2k mice immunized with I-Ab-transfected L cells (H-2k), that are stimulated by L cells transfected with I-Ab, I-Ak or I-Eb, but not by non-transfected L cells. These hybridomas could not be stimulated by spleen cells from H-2i3, H-2k, H-2b or H-2d mice. Monoclonal anti-I-A antibodies did not block their responses, suggesting that mouse major histocompatibility complex (MHC) class II molecules may be peptide donors rather than restriction elements for them. The stimulation of these hybridomas by fibroblast targets was not blocked by an anti-H-2kk, Dk-specific monoclonal antibody. Lipopolysaccharide (LPS)-activated splenic and peritoneal exudate cells from H-2k, H-2d, H-2i3, H-2b as well as beta 2-microglobulin-deficient, TAP-1-deficient and I-A alpha-deficient H-2b mice stimulated these hybridomas. LPS could also activate a macrophage cell line, but not a B-cell line, to become stimulatory for 1E3. A rat antiserum against untransfected L cells specifically and significantly blocked the response of 1E3. Thus, 1E3 may recognize a conserved murine MHC class II peptide loaded in a TAP-1-independent fashion on a non-classical, monomorphic, beta 2-microglobulin-independent restriction element.

Animals↗

Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus: prospective assessment with implications for enhancing compliance.

Non-compliance with therapy is a significant problem, particularly when the disease process is chronic and therapeutic regimens are employed for prolonged periods. We assessed the prevalence and variables associated with compliance with antiretroviral therapy in patients with human immunodeficiency virus infection, by means of a longitudinal observational study of 46 patients aged 23 to 68 years, with human immunodeficiency virus infection, followed at the Pittsburgh VA Medical Center. Data on demographics, medical status, physical functioning (Karnofsky performance scores), CD4 lymphocyte count, depression (Beck depression inventory), coping (inventory of coping with illness scale scores), and psychological and emotional stress (profile of mood states scale scores), were prospectively assessed on all patients at baseline and every 6 months. Compliance was assessed at 6 and 12 months: patients taking > or = 80% of antiretroviral therapy were considered compliant. Overall, 63% of patients were compliant with antiretroviral therapy. Age, education, employment, religious support, and perceived quality of life did not correlate with compliance. By univariate analysis, lack of prior intravenous drug use was significantly associated with compliance (p = 0.01). Compliant patients had significantly better adaptive coping (p = 0.03), and less depression (p = 0.04). By multivariate analysis, black race was significantly associated with non-compliance independent of intravenous drug use and educational status. History of prior opportunistic infection (which presumably heightens the perceived severity of illness) (p = 0.02), and lesser psychological disturbance scores (p = 0.02) were associated with compliance. Compliance was observed despite the greater number of prescription medications taken by compliant patients (p = 0.04). At 12 months, Karnofsky scores were better in compliant patients (p = 0.02), although mortality was not different. Besides identifying predictors of compliance, our data suggest that symptoms of depression and psychological stress be sought in patients with non-adherence.

Activities of Daily Living↗

Low-dose fluconazole as primary prophylaxis for cryptococcal infection in AIDS patients with CD4 cell counts of < or = 100/mm3: demonstration of efficacy in a positive, multicenter trial.

The efficacy of low-dose fluconazole (200 mg orally administered thrice weekly) as primary prophylaxis for cryptococcal infection was prospectively assessed in a multicenter trial involving 218 patients who were infected with human immunodeficiency virus (HIV) and who had CD4 cell counts of < or = 100/mm3. The median CD4 cell count at baseline was 39/mm3, 58% of the patients had an AIDS-defining illness or infection prior to enrollment. Cryptococcal meningitis occurred in 0.4% (1) of the 218 patients. The breakthrough isolate was susceptible to fluconazole, and the fluconazole kinetic study demonstrated adequate drug absorption and serum fluconazole levels; noncompliance could not be excluded in this case. Mucocutaneous and/or esophageal candidiasis developed in 18% (40) of the patients. Noncompliance with fluconazole therapy was the only variable independently associated with breakthrough candidiasis in the study patients (P = .00002). Thus, fluconazole (200 mg thrice weekly) given to HIV-infected patients with CD4 cell counts of < or = 100/mm3 was efficacious as primary prophylaxis for cryptococcosis, with notably lower costs and increased convenience for patients in comparison with daily administration of the drug.

AIDS-Related Opportunistic Infections↗

Porokeratosis.

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Humans↗

Lymphomatoid granulomatosis: evidence that some cases represent Epstein-Barr virus-associated B-cell lymphoma.

Lymphomatoid granulomatosis is currently classified as part of a spectrum of angiocentric immunoproliferative lesions. These were initially thought to be of T-cell phenotype, but recent papers have shown that some cases are B-cell proliferations, sometimes associated with Epstein-Barr virus infection. We reviewed the clinicopathological features of 16 patients with pulmonary lymphomatoid granulomatosis, using immunohistochemistry to assess the phenotype of the infiltrate, the polymerase chain reaction to look for immunoglobulin heavy chain and T-cell receptor gene rearrangements, and in-situ-hybridization to look for Epstein-Barr virus infection. In seven of seven cases the atypical lymphoid population was of B-cell phenotype, with four cases showing evidence of either monoclonality or oligoclonality. All seven cases, including those that lacked unequivocal proof of malignancy, behaved aggressively. Epstein-Barr virus RNA was detected in four cases. We conclude that some cases of lymphomatoid granulomatosis are B-cell lymphomas, sometimes associated with Epstein-Barr virus infection.

Adult↗

HLA antigen expression in enteropathy associated T cell lymphoma.

AIMS: To investigate the occurrence of abnormal patterns of HLA-ABC and HLA-DR expression in enteropathy associated T cell lymphoma and to relate such abnormalities to the Epstein Barr virus (EBV) status of the tumours. METHODS: Eleven enteropathy associated T cell lymphomas were immunostained with HC10 (HLA-ABC heavy chain) and TAL 1B5 (HLA-DR alpha chain) monoclonal antibodies and polyclonal anti-beta 2 microglobulin (beta 2m, the HLA-ABC light chain) antibodies. In situ hybridisation for EBV using EBER probes was performed on all cases. RESULTS: Tumour cells of two of 11 patients were EBER positive. One of these showed partial, and the other, complete loss of beta 2m. HLA-DR expression was undetectable in both patients. Of the remaining nine EBER negative tumours, two were HLA-ABC heavy chain negative or showed only occasional positive cells and five of nine showed partial or complete loss of the HLA-ABC light chain, beta 2m. Seven of the nine cases were either negative for HLA-DR or showed weak expression in a proportion of tumour cells. CONCLUSIONS: These data show that low or absent HLA-ABC and HLA-DR antigen expression occurs commonly in enteropathy associated T cell lymphoma. These abnormal patterns of HLA expression may be associated with escape from immune attack which, in a minority of patients, could be directed against EBV antigens.

HLA-A Antigens↗

Fever of unknown origin: a prospective study.

Fever of unknown origin (FUO) is a problem frequently faced by clinicians all over the world. One hundred and twenty-one cases of FUO presenting to a large teaching hospital in northern India were prospectively studied over a period of 2 years. Infections were the commonest cause accounting for 43.8% cases of FUO, with tuberculosis (TB) being the commonest infection encountered. Collagen vascular diseases and tumours accounted for 15.7 and 8.3% cases, respectively. No cause could be found out in a substantial number of cases (19%) even after invasive investigations. Knowledge of the current patterns of FUO is important since many patients present with potentially treatable diseases.

Adult↗

Orthotopic liver transplantation in U.S. veterans under primary tacrolimus immunosupression.

The evolution and refinement of surgical techniques, per ioperative patient care, and immunosuppression hav~ estab~ished orthoto~ic li~er transplantation (OLTX) as a ~ighly successful therapeutic modality for patients wrth end-stage hver disease. In February 1989,Tacrohmus (Prograf®, formerly FK 506)was first used successfully at the University of Pittsburgh Medical Center to treat patients with rejection refractory to cyclosporine-based immunosuppression." Clinical trials utilizing Tacrolimus in solid organ transplantation followed, and in April of 1994 it was approved for use by the Food and Drug Administration,

Journal Article↗