Biomedical subjects

N Schluger

Publications and source records attributed to N Schluger.

10 recordsLinked to original sources

PubMed2006

Mortality in a large tuberculosis treatment trial: modifiable and non-modifiable risk factors.

SETTING: North America. OBJECTIVES: Tuberculosis (TB) patients in North America often have characteristics that may increase overall mortality. Identifying modifiable risk factors would allow for improvements in outcome. DESIGN: We evaluated mortality in a large TB treatment trial conducted in the United States and Canada. Persons with culture-positive pulmonary TB were enrolled after 2 months of treatment, treated for 4 more months under direct observation, and followed for 2 years (total observation: 28 months). Cause of death was determined by death certificate, autopsy, and/or clinical observation. RESULTS: Of 1075 participants, 71 (6.6%) died: 15/71 (21.1%) HIV-infected persons, and 56/1004 (5.6%) non-HIV-infected persons (P < 0.001). Only one death was attributed to TB. Cox multivariate regression analysis identified four independent risk factors for death after controlling for age: malignancy (hazard ratio [HR] 5.28, P < 0.0001), HIV (HR 3.89, P < 0.0001), daily alcohol (HR 2.94, P < 0.0001), and being unemployed (HR 1.99, P = 0.01). The risk of death increased with the number of independent risk factors present (P < 0.0001). Extent of disease and treatment failure/relapse were not associated with an increased risk of death. CONCLUSIONS: Death due to TB was rare. Interventions to treat malignancy, HIV, and alcohol use in TB patients are needed to reduce mortality in this patient population.

Adult↗

PubMed2001

Characterization of the secreted MPT53 antigen of Mycobacterium tuberculosis.

MPT53 is a secreted protein of Mycobacterium tuberculosis. Southern transfer and hybridization showed mpt53 to be conserved in the M. tuberculosis complex and to have homology with DNA from Mycobacterium avium and other nontuberculous mycobacteria. However, anti-MPT53 polyclonal antibodies detected no antigen in the culture filtrates of M. avium and other nontuberculous mycobacteria. MPT53 of M. tuberculosis induced strong, tuberculosis-specific antibody responses in guinea pigs but induced no delayed-type hypersensitivity. Involvement in immune responses during human tuberculosis was very modest.

Animals↗

PubMed1998

Valvular endocarditis due to Mycobacterium tuberculosis.

Granulomas due to Mycobacterium tuberculosis are rarely observed in valvular structures. When observed, they are associated with disseminated tuberculosis in immunocompromised patients. We report the first case of tuberculous valvular endocarditis isolated in an immunocompetent patient. The patient had severe mitral valve regurgitation due to a perforation of the anterior leaflet of the mitral valve. M. tuberculosis was cultured from the vegetations and no other tuberculous foci were identified. This case exemplifies the protean manifestations of M. tuberculosis infections.

Endocarditis, Bacterial↗

PubMed1997

Widespread dissemination of a drug-susceptible strain of Mycobacterium tuberculosis.

In New York City, a large proportion of new tuberculosis cases has been caused by 1 drug-susceptible strain (called C strain) of Mycobacterium tuberculosis. Between 1991 and 1994, among >600 tuberculosis patients consecutively identified in four large hospitals in the city, 54 with C strain, 69 with non-C cluster pattern strains, and 42 with noncluster pattern strains were studied. Susceptibility to reactive nitrogen intermediates (RNI) of selected isolates was compared. In a case-control analysis, 51% of patients with C strain, 28% with non-C cluster strains (P < .05), and 14% with noncluster strains (P < .01) were found to be injection drug users. C strain but not 13 other unrelated isolates were resistant to RNI. Injection drug use may provide a selective pressure for an RNI-resistant tubercle bacillus to emerge, which may give the organism a biologic advantage and explain the widespread dissemination of C strain M. tuberculosis within the city.

Adolescent↗

PubMed1995

Human host response to Mycobacterium tuberculosis.

Despite the importance of tuberculosis as the leading cause of death due to infectious disease in the world, it has only been recently that an understanding of the human host response in this infection has begun to emerge. The key components of this response are cytokines and components of cellular immunity, predominantly T-lymphocytes and macrophages. Though the relationships among the components of the immune response are complex, it seems likely that in response to mycobacterial infection associated with active disease, cytokines such as TNF-alpha and IL-1 beta are produced; these cytokines serve to recruit more lymphocytes, generally of the T(H) (T helper) phenotype, which then produces substances such as the macrophage activating factor interferon-gamma. Macrophages activated by IFN-gamma ar thus stimulating to enhance intracellular killing of mycobacteria. The role of other cytokines, such as IL-6 and IL-8, both of which are induced by M. tuberculosis or its cell was components, is less clear. Further elucidation of the human host response to tuberculosis should help in the development of new vaccines and treatment strategies.

Cytokines↗

PubMed1995

Comprehensive tuberculosis control for patients at high risk for noncompliance.

The current tuberculosis epidemic in the United States is marked, in many areas, by high rates of noncompliance with antituberculous regimens. In response to this, a comprehensive program of medical, nursing, social services, and supervised therapy was developed at Bellevue Hospital. Most patients were referred to the on-site directly observed therapy program (DOT) located in the hospital. Patients on DOT received daily or twice weekly therapy, and were given incentives to enhance compliance. Outreach was used to track patients who missed appointments. From November 1992 through July 1993, 113 patients were referred. HIV infection, homelessness, illicit drug use, and alcoholism were common. Follow-up revealed that 11 patients were noncompliant and completely lost to follow-up; of the remaining 102, 99% achieved bacteriologic cure. Of the 102 patients who received therapy, 74 attended the Bellevue DOT clinic, 16 attended other DOT programs in the city or received medication at home, and three died of HIV-related, nontuberculous illness. Nine patients were self-medicated and judged treatment successes. We conclude that a comprehensive hospital-based tuberculosis control program is capable of achieving a high degree of success, even in a population at high risk for noncompliance.

Adult↗

PubMed1994

Diagnosis of pulmonary embolism at a large teaching hospital.

Pulmonary embolism (PE) is a common clinical entity, although the signs and symptoms that accompany it are nonspecific. This has led to the development of several diagnostic algorithms for diagnosis of PE. These approaches combine noninvasive tests such as ventilation/perfusion (V/Q) lung scanning, impedance plethysmography, and ultrasound, with invasive techniques such as venography and pulmonary angiography. To investigate the manner in which clinicians select and use these various diagnostic strategies, we retrospectively reviewed 316 consecutive cases of suspected PE to determine the sequence and type of diagnostic strategy employed by clinicians. We found that in the majority of cases, physicians chose not to further pursue a diagnosis of PE if the V/Q scan was nondiagnostic. These results suggest that physician behavior is often at variance with published clinical recommendations and that the implementation of clinical practice guidelines needs to be further examined.

Angiography↗

PubMed1993

DNA amplification in experimental pneumocystosis: characterization of serum Pneumocystis carinii DNA and potential P. carinii carrier states.

DNA amplification has identified P. carinii DNA in diverse biologic specimens, including the serum of patients with P. carinii pneumonia. To further examine the relationship between P. carinii DNA in serum and P. carinii infection, the corticosteroid-treated rat model of pneumocystosis was studied. By 4 weeks of immunosuppression, P. carinii DNA was detected in rat lungs and by 6 weeks, in their serum. P. carinii DNA persisted in lung tissue as long as 5 months after the withdrawal of steroids. Serum DNA disappeared 2 weeks after steroids were withdrawn. Nonimmunocompromised, sentinel rats housed near immunocompromised, P. carinii-infected rats also were studied. Within 6 weeks, P. carinii DNA became detectable in lung and by 8 weeks, in serum. P. carinii DNA disappeared rapidly from lungs and sera after sentinel rats were isolated away from corticosteroid-treated rats. These findings support the contagious transmission of P. carinii and suggest facile development of P. carinii carrier states.

Animals↗

PubMed1992

Application of DNA amplification to pneumocystosis: presence of serum Pneumocystis carinii DNA during human and experimentally induced Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia is a leading cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). Much remains unknown about the basic biology of P. carinii and studies of this infection have been hampered by the lack of cultivation methods. We developed a sensitive and specific assay for P. carinii by utilizing DNA amplification of the P. carinii dihydrofolate reductase (DHFR) gene. By this method, P. carinii DNA was detected in the lungs of rats with experimentally induced P. carinii pneumonia 2 wk before the onset of histopathological changes. DNA amplification analysis of serum demonstrated that by 10 wk of corticosteroid treatment, 12 of 12 (100%) infected rats had circulating DHFR DNA. P. carinii DHFR DNA also was detected in the serum of patients with AIDS and active P. carinii pneumonia (12 of 14 sera collected prospectively). Patients with advanced AIDS but without a history of P. carinii pneumonia were negative by this assay (0 of 6 sera examined). Serum polymerase chain reaction may facilitate investigations into the natural history and epidemiology of P. carinii infection, provide insight into the pathogenesis of parasite dissemination, and offer a useful, noninvasive diagnostic test for the detection of human pneumocystosis.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Detection of Pneumocystis carinii in serum of AIDS patients with Pneumocystis pneumonia by the polymerase chain reaction.

Amplification of DNA by the polymerase chain reaction (PCR) offers a highly sensitive and specific method for detecting DNA sequences in biological samples. We applied this technology to develop an assay for the P. carinii dihydrofolate reductase (DHFR) gene. This assay was found to be sensitive enough to detect as little as 1 organism-'equivalent' of DHFR DNA. In rats with experimentally-induced P. carinii pneumonia, DHFR DNA amplification demonstrated the presence of pulmonary P. carinii 2 wk prior to the onset of histopathological changes. When rat serum was analyzed by PCR, serum P. carinii DNA was found in 5 of 14 experimental rats. Finally, P. carinii DNA was detected in the serum of 7 of 18 patients (39%) with AIDS and active P. carinii pneumonia. These results suggest that circulating serum P. carinii DNA can be detected frequently in the course of pulmonary infection and may represent a blood-borne phase of infection. The PCR detection of P. carinii DNA provides a useful tool to study the natural history of P. carinii infection and may offer a non-invasive diagnostic procedure in some patients with P. carinii pneumonia.

Acquired Immunodeficiency Syndrome↗