Pure cartilaginous teratoma differentiated of the testis.
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Biomedical subjects
Publications and source records attributed to N Singh.
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Fifty consecutive patients with fever and cirrhosis were prospectively studied to assess if cirrhotic fever was a true clinical entity and to determine its characteristics and outcome. In 20% (10) of the 50 patients, an identifiable source of fever or infection, was not documented (these patients were defined as having cirrhotic fever). The patients with cirrhotic fever were significantly less toxic, as indicated by lower temperature (P = .0001), tachycardia (P = .0005), and tachypnea (P = .05), but had fever for a longer duration (P = .009) than did patients with infectious fever. Patients with cirrhotic fever were significantly less likely to have focal signs or symptoms (P < .0001) or a portal of infection confirmed by culture (P = .0001), as compared with patients with infectious fever. Outcome (at 30-days or long-term) was not different for patients with cirrhotic fever vs.-patients with infectious fever or matched controls who did not have fever. Eight (80%) of the 10 patients with cirrhotic fever underwent transplantation; fever did not recur after transplantation in any of these patients. Thus, fever in up to 20% of the febrile patients with cirrhosis may be attributable to cirrhosis itself; such patients may be spared the ongoing diagnostic maneuvers and unnecessary trials of antibiotics.
Tacrolimus is being increasingly used as an immunosuppressive agent in transplant recipients. The drug is metabolized by the cytochrome P-450 3A system, thus antimicrobials that inhibit or induce these enzymes can alter levels of tacrolimus in the bloodstream. Tacrolimus is potentially nephrotoxic and neurotoxic; the likelihood of toxicity rises as blood levels of the drug increase. Increased tacrolimus levels and subsequent toxicity have been produced by a number of antimicrobial agents that inhibit the cytochrome P-450 3A system. Conversely, drugs with the potential to induce the cytochrome P-450 3A system can reduce the levels of tacrolimus in the blood, leading to increased risk of acute rejection in transplant recipients. Antimicrobial agents that can have adverse effects on renal function may add to the nephrotoxicity of tacrolimus. The potential for drug interactions should be reviewed before antimicrobial agents are prescribed to patients treated with tacrolimus.
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Invasive fungal infections and their risk factors were prospectively assessed in 130 consecutive liver transplant recipients receiving tacrolimus as the primary immunosuppressive agent. Eleven percent (14) of the 130 patients had 17 episodes of invasive fungal infections. These included candidiasis (5%; 6 patients), cryptococcosis (5%; 6), aspergillosis (3%; 4), and chromomycosis (1%; 1). An elevated pretransplantation creatinine level, requirement of dialysis (pretransplantation or posttransplantation), duration of intensive care unit stay after transplantation surgery, and antibiotic use (other than for prophylaxis) within 4 weeks of transplantation were significant risk factors for fungal infections occurring within 100 days of transplantation. For fungal infections occurring after 100 days, persistence of renal dysfunction (serum creatinine level of >2.5 mg/dL at 3 months), dialysis, and histopathologically documented recurrence of hepatitis C virus hepatitis were significant risk factors. Mortality was significantly higher among patients with fungal infections than among all other patients (57% vs. 15%; P = .0009). Our study identified specific risk factors for invasive fungal infections in liver transplant recipients receiving tacrolimus; strategies to prevent fungal infections or to initiate early antifungal therapy might be most effectively targeted at these patients.
Dematiaceous fungi are being increasingly recognized as pathogens in organ transplant recipients. We describe a case of invasive esophagitis due to Cladophialophora bantiana in a small bowel transplant recipient and review a total of 34 cases of infections due to dematiaceous fungi in organ transplant recipients. The median time to the onset of fungal infection after transplantation was 22 months. Clinically, two distinct patterns of infections were observed: 79% of the patients had skin and/or soft-tissue infections or joint infections (predominantly due to Exophiala species), and 21% had systemic invasive infections (predominantly brain abscesses due to Ochroconis gallopavum [Dactylaria gallopava, Dactylaria constricta var. gallopava]). The overall mortality rate among the patients with skin and/or soft-tissue infections or joint infections and the patients with systemic invasive disease was 7% and 57%, respectively; two of five patients with brain abscesses were cured with antifungal therapy. Recognition of infections due to dematiaceous fungi is important since these infections, unlike invasive aspergillosis, may be more amenable to therapy.
The distribution of hepatitis C virus (HCV) genotypes was studied in 202 anti-HCV-positive liver transplant candidates with end-stage liver disease. HCV sequences were successfully amplified from 185 patients: In the first 100, the genotype was determined by direct sequencing in the NS5 region, and in the remaining 85, type-specific primers were used for genotyping. Eighty-five patients (46.0%) were infected with type 1a HCV strains, 52 (28.1%) with type 1b, 14 (7.6%) with type 2b, 13 (7.0%) with type 4, 5 (2.7%) with type 3a, 2 (1.1%) with type 2a, and 1 (0.5%) with type 2c. Thirteen HCV-positive patients (7.0%) could not be genotyped. The relatively low prevalence of genotype 1b in this population of end-stage liver disease patients speaks against postulated higher pathogenicity of this genotype.
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AIMS: To determine whether immunohistochemistry applied to paraffin wax embedded biopsy tissue can be used to distinguish between B-small lymphocytic lymphoma (B-SLL) and mantle cell lymphoma (MCL). METHODS: Formalin fixed, paraffin wax embedded tissue blocks of 12 cases of B-SLL and 12 cases of MCL were retrieved from the files of the Department of Pathology, Southampton University Hospitals Trust. Following antigen retrieval, where appropriate, sections were stained for CD3, CD5, CD20, CD23, CD43, Cyclin D, PGP9.5, and MIB1 using a streptavidin-biotin complex technique. RESULTS: CD20 stained the neoplastic cells of B-SLL and MCL, and CD3 labelled the reactive T cells in these tumours. In B-SLL, the T cells were generally dispersed among the tumour cells, whereas in MCL they often formed bands around tumour cell nodules. CD5 could be detected on T cells, following antigen retrieval. The level of expression on B cells of B-SLL and MCL was generally too low to allow detection in paraffin wax embedded tissues. CD23 stained B-SLL but not MCL. However, it could be detected in only five of the 12 cases of B-SLL. CD43 could be detected in most cases of B-SLL and MCL. It is not, therefore, of value in distinguishing between these tumours. It will, however, help in the differentiation of B-SLL and MCL from other low grade B cell lymphomas, such as follicle centre cell and marginal zone lymphomas. Cyclin D was expressed in all of the MCL but in none of the B-SLL. PGP9.5 showed reactivity in most cases of MCL and much weaker reactivity in B-SLL. The proliferation indexes of MCL were generally higher than those of B-SLL, as measured by MIB1 labelling. Both tumours, however, showed a wide range of values and considerable overlap. CONCLUSION: Staining for Cyclin D is the most reliable immunohistochemical mean of differentiating between B-SLL an MCL. High levels of PGP9.5, expressed in MCL, may be related to the degradation of Cyclin D by the ubiquitin pathway.
We aim to assess the age-related differences in psychological stress and depression in patients with human immunodeficiency virus (HIV) infection. Prospective, longitudinal, observational study of patients with HIV followed at a university affiliated VA Medical Center. Fifty-six consecutive patients with HIV infection aged 19-68 were studied. Data on demographics, living arrangements, education, employment, income, social, religious, and community support, medical status, psychological stress, depression, and coping was assessed at baseline and every 6 months. Instruments for psychological testing included Beck Depression Inventory, Profile Mood Status (POMS) scale and ways of coping scale (inventory of coping with illness scale). Sixty-nine per cent (38/56) of the patients were older than 35 years of age. Older patients exhibited significantly greater emotional and psychological stress; the mean POMS score for older patients was 56.8 as compared to 21.5 for younger patients (P = 0.004). Older patients had significantly greater depression (P = 0.001), higher tension and anxiety (P = 0.005), greater anger and hostility (P = 0.03), greater confusion and bewilderment (P = 0.01), and more fatigue (P = 0.003) as compared with younger patients. Older patients were significantly more likely to have intravenous drug use as an HIV risk factor (P = 0.02), less likely to be employed (P = 0.005), and more likely to use non-traditional therapies (P = 0). Intravenous drug use was an independent predictor of psychological stress in older patients. Patients with HIV, older than 35 years of age, are significantly more likely to suffer from depression and psychological stress; intravenous drug use was an independent predictor of stress. Interventions for the treatment of depression should be especially sought in this subgroup of patients with HIV.
A study was carried out in a highly malarious forested belt of central India (Madhya Pradesh) to evaluate the usefulness of a dipstick antigen-capture assay (ParaSight F) as a diagnostic method for Plasmodium falciparum appropriate for field use. In all, 1,231 patients with fever were screened in parallel with the taking of thick blood smears. The sensitivity and specificity of the dipstick test for detection of P. falciparum were 93% and 92.5%, respectively. Results also indicate that the dipstick test result became negative within seven days after initiation of curative chemotherapy in the majority of cases (95%). Tribal populations in remote forested areas are important reservoirs of P. falciparum that are mostly resistant to standard antimalarial drugs and a source of malaria to the rest of the country. Control of malaria is limited by inaccessibility, lack of medical services, public ignorance of the disease, and other technical problems. In this population, the dipstick assay was found to be highly accurate, simple, and rapid, suggesting that it may be used in remote forested areas without the need for microscopic examination. The simplicity of the dipstick test enabled administration of more effective and expensive antimalarials preventing further buildup and dissemination of resistant parasites and a return of symptoms.
This study describes the changes occurring in vitro in nerve growth factor (NGF) production and expression of p75 by murine Schwann cells and neurofibroblasts, following infection with Mycobacterium leprae and in the presence of macrophage secretory products, using a semiquantitative ELISA. These parameters are compared in two strains of mice, Swiss White (SW) and C57B1/6, as they differ in their response to M. leprae infection; C57B1/6 is the 'resistant' strain. On infection, NGF levels remained unaltered in Schwann cells from both strains, while fibroblasts from C57B1/6 strain showed an increase in NGF production. Expression of p75 by Schwann cells was decreased on infection in both strains of mice. In vivo, this opposing effect of infection on NGF production and p75 expression by Schwann cells and neurofibroblasts may result in suboptimal amounts of NGF reaching neurons of the affected leprous nerves. Macrophage secretory products suppressed the production of NGF by infected neurofibroblasts from SW strain mice and the expression of p75 in Schwann cells from both strains. These results indicate that macrophages do not assist in nerve repair in leprosy and the differences in response to macrophage secretory products in the two strains suggests that different mechanisms of nerve repair operate in SW and C57B1/6 mice and presumably in lepromatous and tuberculoid patients.
Invasive cryptococcal infections have been reported in 0.3-1% of the patients undergoing liver transplantation in the previous reports. In contrast, invasive cryptococcosis developed in 6% of 102 consecutive liver transplants at our institution receiving tacrolimus as primary immunosuppression. Cutaneous and/or osteoarticular infections due to cryptococcus were detected in 67% of the patients with cryptococcosis, whereas meningitis was present only in 17%. One of the six patients with cryptococcosis presented with refractory shock and multiorgan system failure attributable solely to cryptococcosis. Patients with cryptococcal infections were significantly older than all other liver transplant recipients (p = 0.017), suggesting reactivation as opposed to primary infection as pathogenesis of cryptococcosis. 100% of the patients with cryptococcosis resided on the Eastern coast of the United States as compared to 59% of the patients without cryptococcosis (p = 0.08). There was no difference in the severity of underlying liver disease, degree of immunosuppression or CMV infection or disease between patients who did and did not develop cryptococcosis. Atypical manifestations, e.g. cutaneous diseases or sepsis syndrome, as opposed to subclinical meningitis, may be a clinical feature of cryptococcal infection in liver transplant recipients.
Determinants of outcome of intensive care unit (ICU) stay and quality of life in survivors was prospectively assessed in 50 consecutive liver transplant recipients requiring intensive care unit (ICU) management. Variables assessed included demographic, clinical and laboratory characteristics, measures of severity of illness (Child-Pugh, Apache II, and organ system failure scores) and quality of life measures (physical functioning, perceived quality of life, stress, depression, and adaptive coping). Overall ICU survival was 82% (41/50). Nonsurvivors had significantly higher acute physiology scores (p = 0.03). Apache II score (p = 0.03), Karnofsky score (p = 0.01) and serum bilirubin (p = 0.05) on admission than survivors. Nonalert mental status (p = 0.0002), hypothermia (p = 0.035) and hypotension (p = 0.027) on admission were significantly associated with mortality. During the ICU stay, requirement of mechanical ventilation (p = 0.02), duration of ventilation (p = 0.01), requirement of dialysis (p = 0.0005), development of pulmonary infiltrates (p = 0.0001) and infections in the ICU (p = 0.003) were significantly associated with mortality. Requirement of mechanical ventilation was an independently significant predictor of mortality (with mechanical ventilation, dialysis and infections in the logistic regression analysis model). There was no difference in post-discharge quality of life (as assessed by the perceived quality of life, stress, depression, and coping scores) in survivors of ICU stay as compared with patients who never required ICU care. Our study suggests that the ICU management can have a positive impact on outcome for liver transplant recipients. If they survive (and 82% did in this study), their quality of life is unaffected and as good as those whose postoperative course was not complicated by a critical illness requiring ICU care.
Seven Toxoplasma gondii IgM antibody detection kits commercially available in the Indian markets were evaluated for their sensitivity, specificity, predictive values and cost-effectiveness on 140 serum samples (80 sera were positive and 60 negative). Modified direct agglutination test was used as standard. The principals of seven anti-Toxoplasma gondii IgM antibody detection kits were Organon-Teknika (Holland), Eurogenetics (Belgium), Labo Biomedical (Netherlands), Gamma-sa (Belgium), Viro-Immun Labor Diagnostika (Germany), Diamedix (USA) and Melotech (Spain). Of the seven kits, the first 4 were based on mu-capture principle. Organon-Teknika IgM ELISA kit was found to be most accurate, cost-effective and presentable, while Melotech and Viro-immun IgM kits were found unacceptable for clinical diagnosis of toxoplasmosis.
A comparison of the mechanism of action of benzoyl peroxide, a tumor promoter was studied in three different cell lines i.e. NIH 3T3, HDCS and A431. Benzoyl peroxide was found to mediate its effect by inducing poly ADP-ribosylation in all the three cell types studied but to different extents, with histone H1 serving as a common acceptor for poly ADP-ribose. It also stimulated the activities of the antioxidant enzymes CuZn superoxide dismutase and catalase in NIH 3T3 and HDCS cells, but not in A431. Alterations in the expression of c-jun and c-fos were observed in NIH 3T3 and A431 cells. Benzoyl Peroxide appeared to mediate its effect via genetic and epigenetic mechanisms.
HLA has been shown to be associated with many diseases. To find out whether host genetic factors like the HLA are involved in susceptibility to kala-azar (visceral leishmaniasis) in India, we formulated an association study with genetically related controls. All samples were typed by PCR SSOP (sequence specific oligonucleotide probes) for HLA class I (A and B) and class II (DR) antigens. The test of association we used was the transmission disequilibrium test (TDT). No significant evidence for association with any of the three HLA loci was obtained.