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Biomedical subjects

S Bonk

Publications and source records attributed to S Bonk.

At least 19 recordsLinked to original sources

Increasing incidence of Mycobacterium xenopi at Bellevue hospital: An emerging pathogen or a product of improved laboratory methods?

STUDY OBJECTIVES: To investigate the dramatic rise in number of Mycobacterium xenopi isolates identified in our mycobacteriology laboratory, and to determine if this increase was due to emerging clinical pathology or to changes in culture technique. DESIGN: Retrospective chart and laboratory review. SETTING: University-affiliated tertiary-care city hospital. PATIENTS: Eighty-one patients with a single culture positive for M xenopi from 1975 to 1994 (period 1), and 47 patients with two or more cultures positive from 1994 to 1998 (period 2). INTERVENTIONS: The Bellevue mycobacteriology laboratory changed the culture medium from solid Lowenstein-Jensen medium (used from 1975 to 1990) to the Septi-Check AFB System (Becton-Dickinson; Glencoe, MD; used from 1991 to 1994), to the Mycobacteria Growth Indication Tube (MGIT; Becton-Dickinson; used from 1995 to 1998). MEASUREMENTS AND RESULTS: We recovered 29 M xenopi isolates from 1975 to 1990, 12 isolates from 1991 to 1994, and 381 isolates from 1995 to 1998. We subsequently identified and reviewed the medical records of all 81 patients who were culture positive for M xenopi from 1975 to 1994 (period 1), and 46 patients who had two or more isolates culture positive for M xenopi from 1995 to 1998 (period 2). For period 1, 75% of the subjects were male, 80% were minority, and at least 43% were HIV positive. Only one patient had clinical M xenopi lung disease during this period. For period 2, 79% of the subjects were male, 83% were minority, and at least 58% were HIV positive; two additional patients were identified who had clinical M xenopi lung disease. CONCLUSIONS: The dramatic increase in M xenopi isolates noted in our hospital was due to a more sensitive laboratory isolation technique, rather than a true increase in clinical disease. Other hospitals utilizing MGIT systems for mycobacterial recovery should interpret positive M xenopi cultures with caution.

AIDS-Related Opportunistic Infections↗

Low density lipoprotein receptor as a candidate receptor for hepatitis C virus.

Hepatitis C virus (HCV) binds to different human cell lines in vitro. However, the efficiency of adsorption is very low due mainly to a relatively small fraction of the virus being able to bind to these cells. Free low density lipoprotein (LDL > 200 microg/ml) is able to block the attachment of HCV to human fibroblasts in vitro completely. COS-7 cells being primarily not able to bind HCV were transfected with a vector containing the entire coding sequence of the human LDL-receptor (LDLR). HCV was now bound to these cells. We propose that HCV and LDL are competitive for the cellular LDLR and that LDL in sera of patients may regulate the binding of HCV to this target.

Adsorption↗

Risk factors for rifampin-monoresistant tuberculosis: A case-control study.

Rifampin is the cornerstone of short-course chemotherapy for the treatment of tuberculosis (TB). Rifampin monoresistance (RMR) is less common than resistance to isoniazid alone or in combination with other antituberculous medications. We conducted a retrospective case-control study to identify risk factors for RMR-TB. Complete records for 21 of a total of 26 RMR patients from 1990 to 1997 were available for review, and were compared with those of 48 patients with drug-susceptible TB, controlling for year of diagnosis. Cases more frequently had a history of TB than did controls (61% versus 22%, p < 0.01), and were more often human immunodeficiency virus (HIV) positive (81% versus 46%, p = 0.02). With control for HIV status, cases were more likely to have extrapulmonary involvement (47.6% versus 11.6%, p = 0.05). Four cases (19%) and one control (2. 1%) died (p = 0.02) during hospitalization. Cases more often had a history of incarceration (71.4% versus 37.5%, p = 0.09). Among the 13 cases with a history of TB, five had evidence of malabsorption (vomiting and/or diarrhea), versus none of the 11 controls with prior TB. These data support the hypothesis that RMR is seen primarily in individuals with a history of TB and who are HIV positive. Cases were frequently noncompliant with previous treatment for TB, had a history of incarceration, and had poor outcomes.

AIDS-Related Opportunistic Infections↗

Time to detection of Mycobacterium tuberculosis in sputum culture correlates with outcome in patients receiving treatment for pulmonary tuberculosis.

STUDY OBJECTIVE: The purpose of this study was to determine whether the time to detection (TTD) of Mycobacterium tuberculosis in sputum culture correlates with the response to antituberculous treatment in patients with pulmonary tuberculosis. STUDY DESIGN: Twenty-six consecutive patients were studied who had active pulmonary tuberculosis and sufficient sputum cultures and clinical follow-up to allow adequate assessment. RESULTS: Following initiation of antituberculous therapy, 13 patients (group 1, responders) had a complete response to treatment, and the TTD of M tuberculosis using the mycobacterial growth indicator tube increased steadily. The remaining 13 patients (group 2, nonresponders) had persistent evidence of active disease and demonstrated little or no increase in the TTD with treatment unless an additional therapeutic intervention was implemented (surgery, improved compliance with medications, or a change in medications). The presence of HIV infection, intravenous drug use, multidrug resistance, treatment with second-line therapy, extensive radiographic involvement, and cavitary disease were associated with a delayed increase in the TTD. CONCLUSIONS: The TTD was superior to clinical, radiographic, or conventional bacteriologic evaluation in determining treatment outcome. The TTD closely correlates with the overall response to treatment for pulmonary tuberculosis and may represent a useful adjunct to predict outcome in these patients.

Adult↗

Screening by specialists to reduce unnecessary test ordering in patients evaluated for tuberculosis.

STUDY OBJECTIVE: To determine if screening by specialists could reduce unnecessary test ordering and reduce costs related to diagnostic workup in patients undergoing evaluation for tuberculosis. DESIGN: Prospective evaluation of expert opinion in consecutive patients suspected of having tuberculosis. SETTING: A large municipal hospital. PATIENTS: Patients for whom sputum acid-fast smears were ordered. INTERVENTION: For patients from whom sputum acid-fast bacilli smears and cultures were requested, the chest radiograph and a brief clinical history were presented separately to two pulmonologists with considerable experience in tuberculosis. Each expert reviewed each case independently (and was blinded to the opinion of the other) and indicated if he thought sputum smear examination and culture was, in fact, necessary. Final clinical diagnosis and microbiological information were correlated with the experts' opinion. MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients had sputum smears ordered and had chest radiographs available for review. The two experts believed that sputum examination (smear and culture) was indicated in only 51.5% and 52.6% of cases, respectively. Interobserver agreement was 84.4%. Ultimately, six cases of active tuberculosis were diagnosed. Each expert detected all proven cases of tuberculosis, although one case occurred in a patient with a poor quality radiograph about which the experts offered no opinion. CONCLUSIONS: Screening by experienced clinicians may be effective in reducing unnecessary test ordering and reducing costs related to diagnostic workup in patients evaluated for tuberculosis.

AIDS-Related Opportunistic Infections↗

The significance of Mycobacterium avium complex cultivation in the sputum of patients with pulmonary tuberculosis.

Mycobacterium avium-intracellulare complex (MAC) is a ubiquitous environmental microorganism whose pathogenicity ranges from innocuous colonization to disease, in immunocompetent as well as immunocompromised individuals. We sought to determine the clinical significance of MAC in sputum cultures of patients with pulmonary tuberculosis (TB). A retrospective analysis between January 1994 and March 1995 at Bellevue Hospital Center revealed both Mycobacterium tuberculosis and MAC in 35 patients (11% of all patients with TB). Of 27 patients reviewed, 52% were HIV-1 infected (median CD4 + 25 cells per microliter). Radiographic manifestations in patients with TB and MAC were similar to those seen in patients with TB alone. Both mycobacteria were cultured primarily from respiratory sources. M tuberculosis was usually cultured first or concurrent with MAC, and in nearly all cases, both species were recovered within 2 months of each other. Most patients improved clinically, bacteriologically, and radiographically with standard antituberculous therapy, except those with advanced AIDS, multidrug-resistant TB (MDR-TB), or disseminated MAC. We conclude that recovery of MAC in sputum is common in patients with pulmonary TB, regardless of HIV-1 infection, MDR-TB, or other clinical, bacteriologic, or radiographic attributes. MAC cultivation in most of these patients likely represents transient colonization, and in most cases is not clinically significant.

Adult↗

Spinal tuberculosis in patients with human immunodeficiency virus infection: clinical presentation, therapy and outcome.

SETTING: Bellevue Hospital, a large public hospital in New York City. OBJECTIVE: To discern the clinical characteristics of spinal tuberculosis (Pott's disease) in patients with the human immunodeficiency virus (HIV). DESIGN: Review of all cases of spinal tuberculosis seen at the hospital from 1988 to 1995, with comparison of HIV-positive and HIV-negative cases. Chart reviews for all cases were performed and information regarding signs and symptoms, neurological findings, laboratory and radiographic data, medical and surgical treatment and eventual outcome were recorded. RESULTS: We collected 26 cases of tuberculosis of the spine between July 1988 and June 1995. Seven of our 26 patients (27%) were HIV seropositive. Six of these were PPD+ on presentation. When compared with HIV-negative patients, those with HIV and spinal tuberculosis had similar clinical presentations; most patients had a diagnosis made with percutaneous needle aspiration biopsy of clinically involved areas, and open procedures added little diagnostic information. Most were treated without surgery, and response to antituberculosis therapy was uniformly good. CONCLUSION: We conclude that clinical presentations of spinal tuberculosis are similar in HIV-positive and -negative patients, and good outcomes can be expected with regard to mycobacterial disease.

Adult↗

Isolation of the gene for the beta subunit of RNA polymerase from rifampicin-resistant Mycobacterium tuberculosis and identification of new mutations.

Tuberculosis (TB) is one of the most important infections worldwide, with an estimated incidence of 10 million active cases per year. Rifampicin is a key component of the first-line therapy used in the treatment of tuberculosis. In Escherichia coli and Mycobacterium leprae, rifampicin has been shown to inhibit the beta subunit of RNA polymerase. The gene (rpoB) encoding this enzyme has been described in both species. We report the isolation of the homologous functional rifampicin resistance gene from M. tuberculosis. A library was constructed with 15 to 25 kb BamHI-digested DNA fragments from a rifampicin-resistant M. tuberculosis clinical isolate that was ligated into an E. coli-mycobacterial shuttle plasmid. Southern analysis of BamHI-digested DNA from 200 recombinant plasmids was performed and filters were hybridized to a 411 bp fragment of the beta subunit of RNA polymerase from M. tuberculosis. Only DNA from one plasmid (#86) hybridized, which suggested that the gene is found as a single copy per genome. This plasmid was able to transfer rifampicin resistance to sensitive M. smegmatis and thus codes for a functional genetic unit. Sequence analysis in the expected "hotspot" region in eight rifampicin-resistant M. tuberculosis strains (including one multidrug-resistant strain) revealed two novel mutations as well as others previously described.

Cloning, Molecular↗

The third epidemic--multidrug-resistant tuberculosis.

We recently observed a striking increase in multidrug-resistant tuberculosis (MDR-TB) among patients admitted to the Chest Service at Bellevue Hospital Center in New York. We reviewed the laboratory susceptibility test results of 4,681 tuberculosis (TB) cases over the past 20 years, Combined resistance to isoniazid and rifampin increased from 2.5 percent in 1971 to 16 percent in 1991 with higher rates noted for individual drugs. We reviewed the medical records of 100 patients with drug-resistant TB, finding that these individuals were predominantly less than 40 years of age, minority, male, jobless, undomiciled, with a high percentage of drug abuse and human immunodeficiency virus infection. We conclude that the epidemics of AIDS and TB are complicated by a third epidemic of MDR-TB. This third epidemic requires urgent attention to achieve more rapid diagnosis, to develop new therapeutic regimens, and to address the social and hospital environment ot care for these individuals.

Adult↗

Density heterogeneities of hepatitis C virus in human sera due to the binding of beta-lipoproteins and immunoglobulins.

Heterogeneities in the density of hepatitis C virus RNA-carrying material (HCV-RNA-CM) found in human sera (1.03-1.20 g/cm3) are attributed to the binding of low-density lipoproteins and/or of IgG. In some sera HCV-RNA-CM seems to be nearly totally bound to beta-lipoproteins and cannot be precipitated by anti-IgG (gamma); in others more than 95% of HCV-RNA-CM is bound to IgG and cannot be precipitated by anti-beta-lipoprotein. Furthermore, there are sera from which HCV-RNA-CM can be completely be precipitated by either anti-beta-lipoprotein or anti-IgG (gamma), pointing to a binding of the two serum proteins to the same HCV-RNA-CM. There are other sera from which HCV-RNA-CM can be partially precipitated by the one or the other antiserum, leaving behind fractions, which are bound to beta-lipoprotein or to IgG. HCV-RNA-CM cannot be precipitated from some sera either by anti-beta-lipoprotein or by anti-IgG (gamma).

Centrifugation, Density Gradient↗

Association of hepatitis C virus in human sera with beta-lipoprotein.

Hepatitis C virus (HCV)-RNA in sera of patients with viral hepatitis C is supposed to be included, at least partially, into HCV particles. We found that the density of HCV-RNA-carrying material was variable, as determined by sucrose gradient density centrifugation (1.03-1.20 g/cm3). In some of the sera examined HCV-RNA was restricted to low densities between 1.03 and 1.08 g/cm3. In other sera additional densities of HCV-RNA were found distributed over the whole gradient with peaks at 1.12 and 1.17 and at 1.19-1.20 g/cm3. HCV-RNA banding at low densities could be completely co-precipitated with anti-beta lipoprotein, whereas HCV-RNA fractions of higher densities were only partially precipitated or not at all. In 8 of 20 sera directly examined, HCV-RNA could be completely and in 9 sera only partially co-precipitated by anti-beta lipoprotein. In 3 sera no significant precipitation could be observed.

Acute Disease↗

Screening for respiratory syncytial virus and assignment to a cohort at admission to reduce nosocomial transmission.

To limit nosocomial spread of respiratory syncytial virus (RSV) infection, a longitudinal intervention trial was instituted. Nasal secretions or washes were screened for RSV antigen by enzyme-linked immunosorbent assay, and patients were assigned to an RSV-infected or an RSV-uninfected cohort. The baseline (preintervention) rate of 7.17 nosocomial cases of RSV per 1000 patient-days of care was used for comparison. Despite continued infections in the community after screening was initiated, there were no cases of RSV infection in 1880 patient-days of care for 3 months (p = 0.039). During the fourth month, an RSV-infected child was erroneously assigned to the RSV-uninfected cohort, and three nosocomial cases occurred--5.33/1000 patient-days of care (p = 0.286). Overall, there were three nosocomial RSV infections in 2443 patient-days of care in the 1987 season after screening was introduced--1.23/1000 patient-days of care (p = 0.026). In the subsequent RSV season, there was one nosocomial case--0.461/1000 patient-days of care for 3 months (p = 0.0074). During the same period, nosocomial cases of RSV were observed in the pediatric and neonatal intensive care units, where assignment to a cohort was not possible. We conclude that entry into a cohort at the time of admission, on the basis of prospective RSV screening by enzyme-linked immunosorbent assay, effectively reduces nosocomial transmission of RSV.

Child, Preschool↗

A controlled trial of bovine dialyzable leukocyte extract for cryptosporidiosis in patients with AIDS.

Cryptosporidial infection causes severe diarrheal disease in patients with AIDS. Fourteen patients with AIDS and symptomatic cryptosporidiosis were treated with a specific bovine dialyzable leukocyte extract (immune DLE) prepared from lymph node lymphocytes of calves immunized with cryptosporidia or a nonspecific (nonimmune) DLE prepared from nonimmunized calves. Six of 7 patients given immune DLE gained weight and had a decrease in bowel movement frequency, with eradication of oocysts from stool in 5 patients. Six of 7 patients given nonimmune DLE showed no decrease in bowel movement and 4, no clearing of oocytes from stool; 5 continued to lose weight. Subsequently, 5 of these 7 were treated with immune DLE; 4 had a decrease in bowel movement frequency and significant weight gain, with eradication of oocytes from stool in 2 patients. Immune DLE produces sustained symptomatic improvement in patients with AIDS and active cryptosporidiosis, but lack of an appropriate cryptosporidial antigen allows only postulation that an augmentation of cellular immunity to Cryptosporidium parvum induced by immune DLE resulted in the microbiologic and clinical improvement observed.

Acquired Immunodeficiency Syndrome↗

Bacterial infections in human immunodeficiency virus-infected children.

A retrospective review of 71 children infected with human immunodeficiency virus cared for over a 3.5-year period revealed that 44 of 71 (63%) required a bacterial culture and 27 of 71 (37%) had bacteriologically documented infection. There were 125 episodes in 27 patients. Pneumonia (24 of 125 (19%)), upper respiratory tract syndromes (23 of 125 (19%)), urinary tract infection (24 of 125 (19%)) and wound infection (12 of 125 (10%)) were the most common syndromes identified. Bacteremic infections occurred in 35 of 125 (28%), and in 17 of 125 (14%) no other primary source could be identified. Pneumococci (11 of 35 (31%)) and Salmonella (4 of 35 (11%)) were the most common blood isolates; however, a wide spectrum of Gram-positive and Gram-negative pathogens were recovered. Bacterial pneumonia directly contributed to the death of 4 patients, in whom pneumonia caused by Pneumocystis carinii (2), cytomegalovirus (1) or varicella-zoster virus (1) also coexisted, respectively. Absolute T4 counts less than 400 and depressed lymphocyte-proliferative responses to diphtheria and tetanus toxoids, Candida antigen and pokeweed mitogen correlated with the occurrence of bacterial infection in human immunodeficiency virus-infected children. Although bacterial infections are a frequent cause of morbidity in human immunodeficiency virus-infected children, they are usually treatable.

Acquired Immunodeficiency Syndrome↗

Treatment of cryptosporidiosis with oral bovine transfer factor.

Cryptosporidia are intestinal protozoans long known to cause diarrhea in humans, especially those with acquired immune deficiency syndrome (AIDS). When transfer factor prepared from calves which possessed delayed-type hypersensitivity to Eimeria bovis was given to nonimmune calves and mice it conferred protection against clinical infection (coccidiosis). Recent studies with oral bovine transfer factor have shown that it can confer cell-mediated immunity to humans. Based on these findings we decided to treat eight AIDS patients suffering from Cryptosporidium-associated diarrhea with transfer factor prepared from calves immune to Cryptosporidium. Prior to treatment with transfer factor, three patients had been treated with spiramycin, one patient with alpha-difluoromethylornithine (DFMO), and one patient with furazolidone for greater than 1 month without clinical or laboratory improvement. Following administration of transfer factor, five or eight patients exhibited a decrease in the number of bowel movements and the development of formed stools. Cryptosporidium was eradicated from the stools of four patients but two of these patients subsequently relapsed and one patient continued to have diarrhea despite the absence of Cryptosporidium in the stool. One patient has been free of diarrhea and Cryptosporidium for 2 years after discontinuation of transfer factor therapy.

Acquired Immunodeficiency Syndrome↗