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Biomedical subjects

C Woodley

Publications and source records attributed to C Woodley.

13 recordsLinked to original sources

Use and efficacy of tuberculosis infection control practices at hospitals with previous outbreaks of multidrug-resistant tuberculosis.

OBJECTIVE: To evaluate the implementation and efficacy of selected Centers for Disease Control and Prevention guidelines for preventing spread of Mycobacterium tuberculosis. DESIGN: Analysis of prospective observational data. SETTING: Two medical centers where outbreaks of multidrug-resistant tuberculosis (TB) had occurred. PARTICIPANTS: All hospital inpatients who had active TB or who were placed in TB isolation and healthcare workers who were assigned to selected wards on which TB patients were treated. METHODS: During 1995 to 1997, study personnel prospectively recorded information on patients who had TB or were in TB isolation, performed observations of TB isolation rooms, and recorded tuberculin skin-test results of healthcare workers. Genetic typing of M tuberculosis isolates was performed by restriction fragment-length polymorphism analysis. RESULTS: We found that only 8.6% of patients placed in TB isolation proved to have TB; yet, 19% of patients with pulmonary TB were not isolated on the first day of hospital admission. Specimens were ordered for acid-fast bacillus smear and results received promptly, and most TB isolation rooms were under negative pressure. Among persons entering TB isolation rooms, 44.2% to 97.1% used an appropriate (particulate, high-efficiency particulate air or N95) respirator, depending on the hospital and year; others entering the rooms used a surgical mask or nothing. We did not find evidence of transmission of TB among healthcare workers (based on tuberculin skin-test results) or patients (based on epidemiological investigation and genetic typing). CONCLUSIONS: We found problems in implementation of some TB infection control measures, but no evidence of healthcare-associated transmission, possibly in part because of limitations in the number of patients and workers studied. Similar evaluations should be performed at hospitals treating TB patients to find inadequacies and guide improvements in infection control.

Adolescent↗

Spread of strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, across the United States.

Strain W, a highly drug-resistant strain of Mycobacterium tuberculosis, was responsible for large nosocomial outbreaks in New York in the early 1990s. To describe the spread of strain W outside New York, we reviewed data from epidemiologic investigations, national tuberculosis surveillance, regional DNA fingerprint laboratories, and the Centers for Disease Control and Prevention Mycobacteriology Laboratory to identify potential cases of tuberculosis due to strain W. From January 1992 through February 1997, 23 cases were diagnosed in nine states and Puerto Rico; 8 were exposed to strain W in New York before their diagnosis; 4 of the 23 transmitted disease to 10 others. Eighty-six contacts of the 23 cases are presumed to be infected with strain W; 11 completed alternative preventive therapy. Strain W tuberculosis cases will occur throughout the United States as persons infected in New York move elsewhere. To help track and contain this strain, health departments should notify the Centers for Disease Control and Prevention of cases of tuberculosis resistant to isoniazid, rifampin, streptomycin, and kanamycin.

Adult↗

Risk factors for rifampin mono-resistant tuberculosis.

Use of rifampin is required for short-course treatment regimens for tuberculosis. Tuberculosis caused by isolates of M. tuberculosis with resistance to rifampin and susceptibility to isoniazid is unusual, but it has been recognized through surveillance. Patients with tuberculosis (cases) with rifampin mono-resistance were compared with HIV-matched controls with tuberculosis caused by a drug-susceptible isolate. A total of 77 cases of rifampin mono-resistant tuberculosis were identified in this multicenter study. Three were determined to be laboratory contaminants, and 10 cases had an epidemiologic link to a case with rifampin mono-resistant tuberculosis, suggesting primary acquisition of rifampin-resistant isolates. Of the remaining 64 cases and 126 controls, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, or history of incarceration. Cases were more likely to have a history of prior tuberculosis than were controls. Of the 38 cases and 74 controls with HIV infection, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, history of incarceration, or prior tuberculosis. Cases were more likely to have histories of diarrhea, rifabutin use, or antifungal therapy. Laboratory analysis of available isolates showed that there was no evidence of spread of a single clone of M. tuberculosis. Further studies are needed to identify the causes of the development of rifampin resistance in HIV-infected persons with tuberculosis and to develop strategies to prevent its emergence.

AIDS-Related Opportunistic Infections↗

Transmission of a highly drug-resistant strain (strain W1) of Mycobacterium tuberculosis. Community outbreak and nosocomial transmission via a contaminated bronchoscope.

CONTEXT: Nosocomial transmission of multidrug-resistant tuberculosis (MDR TB) has been reported primarily in New York State and has generally been presumed to occur via respiratory aerosols. OBJECTIVE: To assess nosocomial transmission of MDR TB. In 1995, 8 patients with MDR TB were identified in South Carolina; all were resistant to 7 drugs and had matching DNA fingerprints (strain W1). Community linkswere identified for 5 patients (Patients 1-5). However, no links were identified forthe other 3 patients (Patients 6-8) except being hospitalized at the same hospital as 1 community patient. DESIGN: Outbreak investigation. SETTING: Community and hospital. PATIENTS: Eight patients whose MDR TB isolates had DNA fingerprint patterns matching strain W1. MAIN OUTCOME MEASURES: Clinical characteristics of patients with strain W1 Mycobacterium tuberculosis isolates. RESULTS: Patient 5 (community patient) and Patient 8, diagnosed April 1995 and November 1995, respectively, had clinical courses consistent with MDR TB, with smear-positive and culture-positive specimens and cavitary lesions on chest radiograph; both died of MDR TB less than 1 month after diagnosis. Patients 6 and 7 (diagnosed May 1995) each had 1 positive culture for MDR TB; specimens were collected during bronchoscopy. Patient 6 had a skin test conversion after bronchoscopy. Neither Patient 6 nor Patient 7 had a clinical course consistent with MDR TB, neither was treated for MDR TB, and both are alive and well. No evidence of laboratory contamination of specimens, transmission on inpatient wards, or contact among patients was found. All 4 received bronchoscopies in May 1995; Patients 6, 7, and 8 had bronchoscopies 1, 12, and 17 days, respectively, after Patient 5. Observations revealed that bronchoscope cleaning was inadequate, and the bronchoscope was never immersed in disinfectant. CONCLUSIONS: Inadequate cleaning and disinfection of the bronchoscope after the procedure performed on Patient 5 led to subsequent false-positive cultures in Patients 6 and 7 and transmission of infection to Patient 6 and active MDR TB to Patient 8.

Aged↗

Outbreak of drug-resistant tuberculosis with second-generation transmission in a high school in California.

BACKGROUND: In spring 1993, four students in a high school were diagnosed with tuberculosis resistant to isoniazid, streptomycin, and ethionamide. METHODS: To investigate potential transmission of drug-resistant tuberculosis, a retrospective cohort study with case investigation and screening by tuberculin skin tests and symptom checks was conducted in a high school of approximately 1400 students. Current and graduated high-school students were included in the investigation. DNA fingerprinting of available isolates was performed. RESULTS: Eighteen students with active tuberculosis were identified. Through epidemiologic and laboratory investigation, 13 cases were linked; 8 entered 12th grade in fall 1993; 9 of 13 had positive cultures for Mycobacterium tuberculosis with isoniazid, streptomycin, and ethionamide resistance, and all 8 available isolates had identical DNA fingerprints. No staff member had tuberculosis. One student remained infectious for 29 months, from January 1991 to June 1993, and was the source case for the outbreak. Another student was infectious for 5 months before diagnosis in May 1993 and was a treatment failure in February 1994 with development of rifampin and ethambutol resistance in addition to isoniazid, streptomycin, and ethionamide. In the fall 1993 screening, 292 of 1263 (23%) students tested had a positive tuberculin skin test. Risk of infection was highest among 12th graders and classroom contacts of the two students with prolonged infectiousness. An additional 94 of 928 (10%) students tested in spring 1994 had a positive tuberculin skin test; 22 were classroom contacts of the student with treatment failure and 21 of these had documented tuberculin skin test conversions. CONCLUSION: Extensive transmission of drug-resistant tuberculosis was documented in this high school, along with missed opportunities for prevention and control of this outbreak. Prompt identification of tuberculosis cases and timely interventions should help reduce this public health problem.

Adolescent↗

Multidrug-resistant tuberculosis in the New York State prison system, 1990-1991.

Three epidemiologically linked multidrug-resistant (MDR) tuberculosis (TB) outbreaks in 1990-1991 involving New York State (NYS) inmates suggested MDR-TB was widespread in NYS prisons. Inmate lists were linked to 1990-1992 TB registries, medical records were reviewed, and movement histories for inmates with MDR-TB were examined within and between prisons and hospitals. In 1990-1991, 171 inmates were diagnosed with TB. This rate (156.2/100,000) was significantly higher than the 1990-1991 US rate (10.4/100,000) and the 1986 rate among NYS inmates (105.5/100,000). Of 171 cases, 155 were cultured-confirmed; 37 (32%) of 116 with drug susceptibilities determined had MDR-TB. Two other inmates with TB before 1990 were diagnosed with MDR-TB in 1990-1991. Of 39 inmates with MDR-TB, 38 (97%) were infected with the human immunodeficiency virus and 34 (87%) have died. These 39 lived in 23 of the 68 NYS prisons while potentially infectious; 12 were transferred through 20 prisons while ill with MDR-TB. Policies of correctional systems on infection control and inmate transfers need to be reevaluated to prevent spread of TB.

Adult↗

Hospital outbreak of multidrug-resistant Mycobacterium tuberculosis infections. Factors in transmission to staff and HIV-infected patients.

OBJECTIVE: To describe transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis infection among patients and health care workers (HCWs) in a ward and clinic for human immunodeficiency virus (HIV)-infected patients in a hospital, four studies were conducted. METHODS: Case patients and control patients were persons who had been treated in the HIV ward or clinic, whose clinical course was consistent with tuberculosis and who had at least one positive culture for M tuberculosis between January 1, 1988, and January 31, 1990, resistant to at least isoniazid and rifampin (case patients), or whose isolates were susceptible to all drugs tested (control patients). In the first study, case patients and control patients were compared to identify risk factors for MDR tuberculosis. In the second study, inpatient and outpatient days of MDR tuberculosis case patients were compared to determine whether acid-fast bacillus (AFB) smear-positivity or aerosolized pentamidine use was associated with higher numbers of subsequent MDR tuberculosis cases among exposed patients. In the third study, restriction fragment length polymorphism analysis was performed on available MDR and sensitive M tuberculosis isolates. In the fourth study, skin test conversion rates among HCWs in the HIV ward and clinic were compared with those of HCWs in another ward, and the strength of the associations between skin test conversions among HCWs on the HIV ward and the number of person-days that AFB smear-positive case patients and control patients were on this ward was estimated. RESULTS: Case patients were more likely than control patients to have been exposed on the HIV ward or clinic to an AFB smear-positive case patient (P less than .001). Inpatient and outpatient days of MDR tuberculosis case patients were associated with more subsequent cases of MDR tuberculosis if exposing case patients were smear-positive or if they received aerosolized pentamidine (P less than or equal to .01). Of 13 MDR isolates, all had one of two restriction fragment length polymorphism patterns; 10 sensitive isolates had restriction fragment length polymorphism patterns that were different from each other. The HCW skin test conversion rate was higher on the HIV ward and clinic than on the comparison ward (P less than .01). The risk of occupational acquisition of infection increased in direct proportion to the number of person-days that AFB smear-positive case patients were on the HIV ward (r = .75; P = .005), but did not increase in proportion to the number of person-days that AFB smear-positive control patients were there (r = -.36; P = NS). After isolation measures for AFB smear-positive tuberculosis patients were improved, MDR tuberculosis cases decreased to seven of 214 tuberculosis patients. CONCLUSIONS: Nosocomial transmission of MDR M tuberculosis infection to patients and HCWs occurred on the HIV ward and clinic. Infectiousness of MDR tuberculosis case patients was associated with AFB sputum-smear positivity. Case patients with MDR tuberculosis created a greater risk of skin test conversion for HCWs on the HIV ward than drug-susceptible control patients.

Adult↗

Rapid purification of tissue inhibitor of metalloproteinases from human plasma and identification as a gamma-serum protein.

A rapid method is described for the purification of human tissue inhibitor of metalloproteinases (TIMP) from plasma which involves immuno-affinity chromatography and gel filtration. The purified plasma inhibitor is immunologically identical with the TIMP previously purified from human amniotic fluid, human synovial fluid and human fibroblast culture medium. It is proposed that this inhibitor is identical with the plasma inhibitor previously named 'B1 anticollagenase', although the plasma inhibitor was shown to migrate as a gamma-serum component.

Blood Proteins↗

Identification of tissue kallikrein in brain and in the cell-free translation product encoded by brain mRNA.

A monoclonal antibody against purified rat urinary kallikrein was coupled to agarose and used to isolate kallikrein from rat brain. The purified enzyme has N alpha-tosyl-L-arginine methyl esterase activity with a pH optimum at 9.0, kinin-releasing activity from a purified low molecular weight kininogen, and a parallelism with standard curves of rat urinary kallikrein in a direct radioimmunoassay. Brain kallikrein is inhibited by a series of tissue kallikrein inhibitors with IC50 values similar to those for urinary kallikrein. The purified brain enzyme was labeled with [14C]diisopropylphosphorofluoridate and visualized by fluorography on a sodium dodecyl sulfate-polyacrylamide gel. Electrophoretic mobility of the enzyme was closely similar to that of urinary kallikrein with estimated Mr of approximately 38,000. With Western blot analyses using a rabbit anti-kallikrein antibody, both brain and urinary kallikrein were visualized at identical positions by immunoperoxidase staining and by autoradiography with 125I-protein A binding. Brain mRNA was used to direct cell-free protein synthesis in wheat germ and rabbit reticulocyte lysate systems. [35S]Methionine-labeled kallikrein was identified by fluorography of sodium dodecyl sulfate-polyacrylamide gels after the translation products were subject to immunoprecipitation with affinity-purified kallikrein antibody. Collectively, the data show that tissue kallikrein exists in brain and can be synthesized by brain mRNA.

Animals↗

Effect of intravenous epinephrine on cerebral cortical blood flow, oxygen tension, and high-energy phosphate metabolism after hypoxic hypotension.

An experimental model was examined in which rats were subjected to 30 minutes of hemorrhagic hypotension and hypoxia. In addition to resuscitation by infusion of blood and saline and increasing the fraction of inspired oxygen (FIO2), the possible beneficial effects of including intravenous epinephrine as part of the resuscitative regimen were studied. Mean arterial pressure, cortical microflow, and brain tissue oxygen tension were increased after epinephrine (P less than 0.05). Cortical ATP concentration was decreased after hypoxic hypotension and failed to improve after epinephrine.

Adenosine Diphosphate↗

Effects of hypoxia and hypotension on oxygen delivery in the brain.

Failure of microvascular re-perfusion, no reflow, of the brain after a period of ischemia has been proposed as the etiology of the cerebral dysfunction frequently seen in patients after resuscitation from hemorrhagic shock. For this investigation rats were stressed by subjecting them to a period of combined hypoxia and hypotension followed by resuscitation. Micro-oxygen electrodes measured brain oxygen tension, thus allowing an assessment of the distribution of cerebral blood flow, during stress and after resuscitation. After resuscitation, a hyperemic response was noted, followed by gradual return of some areas of the brain to normal perfusion, while other areas remained hyperemic for at least 2 hours post-resuscitation. On the basis of these results there appears to be no support for the no-reflow hypothesis. These data imply that therapeutic modalities aimed at increasing cerebral blood flow and oxygenation in the post-resuscitation period are insufficient in themselves for improved survival of patients sustaining a hypotensive, hypoxic episode.

Animals↗