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Biomedical subjects

S V Goldberg

Publications and source records attributed to S V Goldberg.

12 recordsLinked to original sources

Outbreak of tuberculosis in a homeless population involving multiple sites of transmission.

SETTING: During 2002-2003, a large outbreak of tuberculosis (TB) occurred among persons using multiple homeless facilities in King County, Washington. OBJECTIVE: To control the transmission of TB in multiple settings. DESIGN: In 2002, contacts exposed to patients in homeless facilities were screened using tuberculin skin tests (TSTs) and symptom review. Based on these screening results, sites of transmission were identified and prioritised, and exposed cohorts at these sites were offered intensive screening tests in 2003 (e.g., symptom review, TST, chest radiograph [CXR], sputum examination and culture). Mycobacterium tuberculosis isolates from patients were genotyped using PCR-based methods to identify outbreak-associated patients quickly. RESULTS: During 2002-2003, 48 (15%) of 313 patients diagnosed in King County were outbreak-associated; 47 culture-positive patients had isolates that matched the outbreak strain by genotyping. Three facilities visited by >12 patients in 2002 had a higher prevalence of TST positive results (approximately 30%) among clients compared with the background rate (7%) in the homeless community. Screening contacts with one sputum culture was as sensitive as CXR in detecting TB disease (77% vs. 62%, respectively). CONCLUSIONS: A comprehensive, resource-intensive approach likely helped to control transmission. This outbreak highlights the vulnerability of homeless populations and the need to maintain robust TB programs in urban settings.

Adult↗

Cultural case management of latent tuberculosis infection.

SETTING: The proportion of tuberculosis (TB) among foreign-born individuals in the United States is steadily increasing. Treatment of latent TB infection can prevent future cases of disease, although generally only 60% of patients who start a 6-month regimen of isoniazid complete therapy. OBJECTIVE: Cultural case management--employing case manager cultural mediators who serve patient-defined needs in addition to performing TB control functions--may improve results of testing and treatment in one high-risk group, new refugees. DESIGN: A cultural case management approach was established for finding and treating latent TB infection among three groups of new refugees: from the former Soviet Union (FSU), former Yugoslavia (FY), and Somalia. RESULTS: From July 1999 through December 2000, treatment was offered to 442 refugees, of whom 389 (88%) started and 319 (82%) completed therapy. The completion rate among starters from the FSU was 76%, for those from FY it was 94% and for those from Somalia it was 88%. Among all refugees to whom treatment was offered, 319/442 (72%) completed therapy. CONCLUSION: Cultural case management may be a useful tool for expanding treatment of latent TB infection among foreign-born individuals.

Antitubercular Agents↗

Analysis of the frequency distribution of tuberculin skin test readings: a tool for the assessment of group contact investigations.

SETTING: The public health tuberculosis control program covering Seattle, Washington, and its surrounding suburban areas. OBJECTIVE: To describe a tool of potential usefulness in the assessment of transmission of tuberculosis in contact investigations of groups, such as co-workers or schoolmates of an infectious case, with a low prior probability of latent tuberculosis infection (LTBI). DESIGN: Tuberculin skin test (TST) readings in mm of the group being tested were graphed and compared with the known frequency distributions of TST readings of populations with and without LTBI, the latter including a fraction with non-specific tuberculin reactivity. RESULTS: Four group contact investigations were analyzed retrospectively with this tool. In two the graphed TST readings of contacts fell within the distribution of a population with LTBI, and suggested that transmission had occurred. In the other two, the graphed readings better fit the distribution of a population with non-specific tuberculin reactivity and suggested that transmission had not occurred. CONCLUSION: This simple tool to facilitate the determination of whether transmission of tuberculosis has occurred, and who should be offered treatment for LTBI in contact investigations of groups of people, deserves further study.

Adolescent↗

Treatment of isoniazid-resistant tuberculosis with isoniazid, rifampin, ethambutol, and pyrazinamide for 6 months.

SETTING: In 1992 the Seattle-King County Department of Public Health Tuberculosis Clinic began to treat patients with isoniazid-resistant tuberculosis with a regimen of isoniazid, rifampin, pyrazinamide, and ethambutol daily for 6 months. OBJECTIVE: To conduct a review of clinical and bacteriological outcomes of treatment for patients who received the four-drug, 6-month regimen for isoniazid-resistant tuberculosis. DESIGN: A retrospective review of medical records of TB cases meeting the study criteria, a Mycobacterium tuberculosis isolate resistant to isoniazid, and intent to treat with a 6-month course of isoniazid, rifampin, pyrazinamide, and ethambutol. RESULTS: Through December 1999, 44 consecutive patients with isoniazid-resistant, rifampin-susceptible tuberculosis were started on the four-drug, 6-month daily regimen. Among 42 patients followed until completion of therapy, three required changes in the regimen due to side effects. There was one case of drug-induced hepatotoxicity. Among 39 patients with pulmonary involvement, 37 converted sputum cultures from positive to negative within 2 months of starting treatment. There were no treatment failures. On passive follow-up of at least 2 years on all patients, two patients relapsed. The single patient with bacteriological relapse did not develop further drug resistance. CONCLUSION: The regimen of isoniazid, rifampin, pyrazinamide, and ethambutol given daily for 6 months produced successful outcomes when used in a public health tuberculosis clinic as routine therapy for isoniazid-resistant tuberculosis.

Adolescent↗

Hepatotoxicity associated with isoniazid preventive therapy: a 7-year survey from a public health tuberculosis clinic.

CONTEXT: Isoniazid preventive therapy for latent tuberculosis (TB) infection has been debated because of the risk of hepatotoxicity. The frequency of hepatotoxicity was 0.5% to 2.0% in early studies but may have changed with new criteria for diagnosis and patient selection. OBJECTIVE: To determine the rate of isoniazid hepatotoxicity in patients managed according to current guidelines and practice standards. DESIGN: Prospective cohort study. SETTING: A public health clinic operated by the TB control program of a city-county public health agency. PATIENTS: A total of 11141 consecutive patients who started a regimen of isoniazid preventive therapy for latent TB infection from January 1989 through December 1995. MAIN OUTCOME MEASURES: The rate of developing symptoms and signs of hepatotoxicity among all persons starting isoniazid preventive therapy, among all those completing therapy, and by age, sex, and race. RESULTS: Eleven patients (0.10% of those starting, and 0.15% of those completing treatment) had hepatotoxic reactions to isoniazid during preventive treatment. The rate of hepatotoxicity in persons receiving preventive therapy increased with increasing age (chi2 for linear trend = 5.22, P=.02) and there were trends toward increased rates in women (odds ratio [OR], 3.30; 95% confidence interval [CI], 0.87-12.45; chi2 = 3.28; P=.07) and in whites (OR, 2.60; 95% CI, 0.75-8.95; chi2 = 3.08; P=.08). CONCLUSIONS: The rate of isoniazid hepatotoxicity during clinically monitored preventive therapy was lower than has been reported previously. Clinicians should have greater confidence in the safety of isoniazid preventive therapy.

Adolescent↗

Four-month, four-drug preventive therapy for inactive pulmonary tuberculosis.

Standard preventive therapy for inactive pulmonary tuberculosis (TB) is 12 mo of isoniazid. Shorter multiple-drug preventive regimens have been proposed. From December 1993 through January 1996 we evaluated a 4-mo, four-drug regimen of preventive therapy for patients with inactive TB, mostly newly arriving immigrants from countries with high rates of TB and of isoniazid resistance. Fifty-three evaluable patients received a 4-mo regimen of isoniazid, rifampin, ethambutol, and pyrazinamide. We compared their completion rate, side effects, and cost of treatment with those of 108 age-matched patients who had received 12 mo of isoniazid at an earlier time. Sixty-eight percent of patients on the 4-mo regimen completed treatment; 69% of those on the 12-mo regimen completed treatment (p = 0.9393). Side effects were more frequent for the 4-mo regimen (30.2%) compared with 12 mo of isoniazid (11.1%) (p = 0. 0027). The cost of providing an uncomplicated, self-supervised regimen was estimated to be almost four times greater for the four-drug regimen compared with isoniazid. These results show that, in terms of compliance, a four-drug, 4-mo regimen had no advantage over standard preventive therapy for persons with inactive pulmonary TB. On the other hand, the shorter, more intensive regimen was associated with more frequent adverse effects and was more costly.

Adult↗

Directly observed isoniazid preventive therapy for released jail inmates.

This study was designed to determine whether an integrated screening program could be implemented that identified persons with latent tuberculosis infection among jail inmates and produced a high rate of completion of isoniazid preventive therapy (IPT) in those persons after their discharge from short-term detention, by means of community-based directly observed preventive therapy (DOPT). From June 1, 1992 through December 31, 1994 inmates in the King County Jail who were from populations at high risk of tuberculosis were screened by means of the tuberculin skin test and those with latent tuberculosis infection were offered IPT. Among 262 inmates receiving IPT upon release from jail, 105 (40%) could not be located after release. Among another 105 enrolled on DOPT, 63 (60%) completed therapy. Among 52 who chose self-supervised isoniazid therapy after release, 15 (29%) completed therapy (chi-square = 13.50, p = 0.0002). Among persons with latent tuberculosis infection detected during screening at a county jail, a postrelease DOPT program resulted in a high rate of immediate loss to follow-up and a low rate of completion of therapy. Based on these results, we suggest that funds for TB control, if limited, should not be diverted to jail-based screening and postrelease DOPT.

Adult↗

Tuberculosis prevention among foreign-born persons in Seattle--King County, Washington.

The purpose of this study was to evaluate the outcomes of classified immigrant and refugee (I&R) screening and of contact investigation (CI) of foreign-born TB cases in Seattle--King County (SKC), Washington. We reviewed I&R evaluations from the SKC TB clinic for 1992-1994 and contact evaluation records for 54 randomly selected U.S.-born and foreign-born pulmonary TB patients from 1993. Among 942 I&R evaluated, 693 (74%) had positive tuberculin skin tests (TST). Preventive therapy (PT) was prescribed for 324 (34%) and treatment for 49 (5%). The remaining 377 were dismissed, of whom 96% did not meet American Thoracic Society PT criteria. Contacts of foreign-born cases were more numerous (6.0 versus 3.4 per case, p = 0.04), and significantly more likely to be TST-positive (50% versus 18%) and to be started on PT (40% versus 23%). The large number of I&R eligible for treatment or PT emphasizes the benefit of prompt evaluation of new arrivals. CI provides an excellent opportunity to screen foreign-born persons at high risk for active TB.

Contact Tracing↗

Diuretic effect of acute hypoxia in humans: relationship to hypoxic ventilatory responsiveness and renal hormones.

Acute hypoxia causes increased sodium and water excretion. Animal studies suggest that this renal response is largely driven by direct peripheral arterial chemoreceptor stimulation, independent of accompanying changes in ventilation and acid-base status. Whether the diuresis and natriuresis observed in humans made acutely hypoxic are caused by peripheral chemoreceptor stimulation is not known, but, if so, we hypothesized that people with a high ventilatory response to hypoxia (high peripheral chemosensitivity) should have greater diuresis and natriuresis than those with a low ventilatory response to hypoxia. The isocapnic hypoxic ventilatory response (HVR) of 16 subjects on a fixed sodium intake was measured, as were their urinary volume and sodium and bicarbonate losses during 6 h of breathing air (in a normobaric environmental chamber) and, on the subsequent day, 12% O2. The isocapnic HVR correlated positively with hypoxic diuresis (r = 0.87) and natriuresis (r = 0.76). In contrast, the isocapnic HVR did not correlate with bicarbonate excretion, despite the expected respiratory alkalosis of acute hypoxia. The magnitude of diuresis and natriuresis with hypoxia did not correlate with changes in circulating aldosterone, renin, atrial natriuretic peptide, vasopressin, or a digoxin-like immunoreactive substance. These findings are compatible with a role of the peripheral arterial chemoreceptors in mediating the renal response to hypoxia in humans. The efferent pathway remains unknown.

Acute Disease↗

Evolution of rifampin resistance in human immunodeficiency virus-associated tuberculosis.

Acquired rifampin resistance without preexisting isoniazid resistance is highly unusual in patients with tuberculosis. The purpose of this report is to describe and characterize that unusual pattern of acquired drug resistance in three patients with human immunodeficiency virus (HIV) infection. The patients originally had Mycobacterium tuberculosis strains that were susceptible to isoniazid and rifampin. During treatment in two patients and after completion of therapy in the remaining one, each patient developed active, rifampin-resistant, isoniazid-susceptible tuberculosis. One patient subsequently developed isoniazid resistance also. Studies on patients' M. tuberculosis isolates using IS6110 restriction fragment length polymorphism typing and rpoB gene sequencing indicated that rifampin resistance in each patient arose during therapy by an rpoB gene mutation in the original M. tuberculosis isolate. Detection of this unusual drug-resistance phenotype in three patients with HIV infection suggests that acquired rifampin resistance is somehow associated with co-infection due to HIV and tuberculosis.

AIDS-Related Opportunistic Infections↗

Brain tissue pH and ventilatory acclimatization to high altitude.

31P nuclear magnetic resonance spectroscopy (31P-NMRS) was performed on brain cross sections of four human subjects before and after 7 days in a hypobaric chamber at 447 Torr to test the hypothesis that brain intracellular acidosis develops during acclimatization to high altitude and accounts for the progressively increasing ventilation that develops (ventilatory acclimatization). Arterial blood gas measurements confirmed increased ventilation. At the end of 1 wk of hypobaria, brain intracellular pH was 7.023 +/- 0.046 (SD), unchanged from preexposure pH of 6.998 +/- 0.029. After return to sea level, however, it decreased to 6.918 +/- 0.032 at 15 min (P less than 0.01) and 6.920 +/- 0.046 at 12 h (P less than 0.01). The ventilatory response to hypoxia increased [from 0.35 +/- 0.11 (l/min)/(-%O2 saturation) before exposure to 0.69 +/- 0.19 after, P = 0.06]. Brain intracellular acidosis is probably not a supplemental stimulus to ventilatory acclimatization to high altitude. However, brain intracellular acidosis develops on return to normoxia from chronic hypoxia, suggesting that brain pH may follow changes in blood and cerebrospinal fluid pH as they are altered by changes in ventilation.

Acclimatization↗

Exercise breathing pattern during chronic altitude exposure.

Breathing pattern in response to maximal exercise was examined in four subjects during a 7-day acclimatisation to a simulated altitude of 4247 m (barometric pressure, PB = 59.5 kPa). Graded exercise tests to exhaustion were performed during normoxia (day 0), and on days 2 and 7 of hypoxia, respectively. Ventilation was significantly augmented in the hypoxic environment, as were both the mean inspiratory flow (VT/TI) and inspiratory duty cycle (TI/TTOT) components of it. VI/TI was increased due to a significant increase in tidal volume (VT) and a corresponding decrease in inspiratory time duration (TI). Throughout a range of exercise ventilation, TI/TTOT was increased due to an apparently greater decrease in expiratory time duration (TE) with respect to TI. In all cases, the relation between VT and TI displayed a typical range 2 behaviour, with evidence of a range 3 occurring at very high ventilatory rates. There was essentially no difference observed in the VT-TI relation during exercise between the normoxic and hypoxic conditions. No significant changes were observed in the breathing pattern in response to exercise within the exposure period (from day 2 to day 7), although there was a discernible tendency to a higher stage 3 plateau by day 7 of altitude exposure.

Acclimatization↗