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Biomedical subjects

L Sacks

Publications and source records attributed to L Sacks.

At least 19 recordsLinked to original sources

Utility of blood cultures and incidence of mycobacteremia in patients with suspected tuberculosis in a South African infectious disease referral hospital.

SETTING: A 500-bed government referral institution for patients with tuberculosis and other infectious diseases in Gauteng, South Africa. OBJECTIVES: To assess the usefulness of BACTEC blood cultures over and above that of other microbiological methods for the diagnosis of tuberculosis in patients who are suspected of suffering from tuberculosis. DESIGN: Mycobacterial blood cultures were obtained from patients presenting with symptoms suspicious of tuberculosis and where there was no clinical evidence of other infectious etiologies, and from patients who had failed tuberculosis treatment. RESULTS: Sixteen (22%) of 71 patients included in the study were positive for Mycobacterium tuberculosis on blood culture, while seven (10%) were positive for M. avium complex (MAC). Twelve (75%) of the patients with tuberculosis and positive blood cultures were however also positive for acid-fast bacilli on sputum smears and eight (50%) were initially diagnosed clinically and radiographically as localized pulmonary tuberculosis. Blood cultures positive for mycobacteria were only found among patients with human immunodeficiency virus infection (HIV). CONCLUSIONS: Bacteremia with M. tuberculosis complex was detected in HIV-infected patients with suspected tuberculosis, even in patients presenting with localized pulmonary infection on initial clinical assessment. Among patients with suspected tuberculosis, blood cultures were useful in diagnosing unsuspected MAC disease, but did not add to the diagnostic yield of conventional tests for tuberculosis used routinely, namely sputum microscopy and culture, or occasional biopsy specimens.

AIDS-Related Opportunistic Infections↗

Phylogenetic analysis of the 5' subterminal region of isolates of Leishmania RNA virus-1.

Leishmania RNA virus-1 (LRV1) is a double-stranded RNA virus present in some Leishmania species. The virus genome consists of a 450-nucleotide, 5' untranslated region (UTR) followed by the coat gene and the RNA-dependent RNA polymerase (RDRP). It has been shown that the 5' end UTR of the genome promotes internal initiation of translation in an in-vitro assay, indicating the presence of an internal ribosomal entry site (IRES) element upstream of the coat gene. The nucleotide sequences of the 5' subterminal regions of six new isolates of LRV1, of different geographical origins, have now been determined. The RNA folding of the 5' subterminal region of LRV1 has been predicted, using a combination of thermodynamic parameters and folding constraints based on nucleotide substitutions. Furthermore, a putative pyrimidine-rich region (a feature unique to all IRES elements), which is complementary to the Leishmania 18S rRNA, has been identified. The significance and relevance of these findings in the context of the function of the 5' UTR of LRV1 as an IRES element are discussed.

Animals↗

Clinical and radiological features of South African patients with tuberculomas of the brain.

Intracranial tuberculomas are a rare complication of tuberculosis that typically occurs in immunocompromised patients not treated previously for tuberculosis. We identified tuberculomas in 12 patients (11 of whom were infected with human immunodeficiency virus) at a hospital in Johannesburg, South Africa. Responses to antituberculous therapy were good, often despite the presence of large lesions, and surgery was not considered necessary in any of the patients.

AIDS-Related Opportunistic Infections↗

Leadership 99. Interview by Terese Hudson.

Cost control, customer service and collaboration among health care sectors rank as top concerns with panelists in H&HN's annual Leadership Report. Efforts to improve community health are a priority, too, but are often frustrated by financial and other constraints. The 16 panelists represent managed care, physicians, and hospitals and health systems.

Attitude of Health Personnel↗

Intergroup comparisons of carpal tunnel dimensions.

Although it is a common disease entity worldwide, idiopathic carpal tunnel syndrome is rarely seen in black South Africans. This study compares anatomic dimensions of the carpal canal in black and white population groups, using computed tomography. No significant anatomic differences were found between the groups tested; thus, other explanations need to be sought to explain the difference in occurrence of carpal tunnel syndrome in these groups. A parameter, the carpal canal index, was defined and may prove useful in future investigations of this region.

Adult↗

CD4+ T lymphocyte counts and patterns of mortality among patients infected with human immunodeficiency virus who were enrolled in community programs for clinical research on AIDS.

CD4+ T lymphocyte measurements are used frequently in clinical practice and have important prognostic implications. In this study, we describe mortality patterns for 5,204 human immunodeficiency virus (HIV)-infected patients classified in different CD4+ cell strata; patients with and patients without a history of disease progression were included. Patients were enrolled in studies sponsored by the Terry Beirn Community Programs for Clinical Research on AIDS of the National Institute of Allergy and Infectious Diseases between September 1990 and December 1993. Over a median follow-up period of 23.6 months, 1,703 of the 5,204 patients died. For those with CD4+ cell counts (/mm3) of < 25, 25-49, 50-99, 100-199, and 200-499, the cumulative mortality rates after 24 months were 72%, 58%, 47%, 27%, and 10%, respectively. The median survival time was 15 months for those with CD4+ cell counts of < 25 cells/mm3; 21 months for those with CD4+ cell counts of 25-49 cells/mm3; and 40 months for patients with CD4+ cell counts of 100-199/mm3. In each CD4+ cell stratum, mortality rates were higher for those with a history of disease progression at entry into the study; across all CD4+ cell strata, mortality was 60% greater (relative risk = 1.6; 95% confidence interval = 1.5-1.8). These data should be useful in planning clinical trials, and they have implications in terms of the frequency with which CD4+ cell counts should be measured to monitor the progression of HIV infection.

Adult↗

Delayed diagnosis of pulmonary tuberculosis in city hospitals.

BACKGROUND: Delays in the diagnosis of tuberculosis may result in increased patient morbidity and in further spread of the disease. We examined the clinical acumen of the medical staff in the diagnosis of tuberculosis and investigated the reasons for delay in the identification and treatment of patients with pulmonary tuberculosis. METHODS: A retrospective chart review was undertaken between July 1985 and June 1988 on all patients with culture-proven pulmonary tuberculosis at two inner city hospitals. Time intervals between admission and the clinical suspicion, diagnosis, and treatment of tuberculosis were determined. Clinical features were evaluated for their effect on these time intervals. RESULTS: Eighty-five patients with culture-proven pulmonary tuberculosis were identified. Tuberculosis was suspected in 36 patients on admission. By the end of 1 week, tuberculosis was confirmed in 50 patients and suspected in 23 others. Twenty percent of patients either died or were discharged before the diagnosis of tuberculosis was made. Older patients (> 65 years) were misdiagnosed more commonly than younger patients (82% vs 48%). Patients without respiratory symptoms were misdiagnosed more frequently (78% vs 49%) than were those with symptoms. Other reasons for delayed diagnosis and treatment included low use of tuberculin skin tests, misinterpretation of unusual chest roentgenograms, and waiting for culture results in patients with negative acid-fast smears. CONCLUSIONS: The diagnosis and treatment of patients with pulmonary tuberculosis is often delayed owing to atypical presentations and slow confirmation by culture. Improved clinical acumen, development of rapid diagnostic tests, and the institution of early empiric therapy are desirable to control this disease.

Adult↗

Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: a controlled clinical trial.

The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.

Age Factors↗

N-acetylneuraminic acid accumulation in a buoyant lysosomal fraction of cultured fibroblasts from patients with infantile generalized N-acetylneuraminic acid storage disease.

Cultured fibroblasts from control individuals and two patients affected with the infantile variant of generalized N-acetylneuraminic acid (NeuAc) storage disease were disrupted by nitrogen cavitation, and the post-nuclear supernatant fractions were subjected to subcellular fractionation on Percoll gradients. Accumulating NeuAc in affected fibroblasts (approx. 150 nmol/mg protein) co-localized with the lysosomal marker N-acetyl-beta-hexosaminidase (Hex), in a fraction with a mean density of 1.035 g/ml. In contrast, more than 70% of the Hex activity of control cells sedimented in comparable gradients with a density of more than 1.07 g/ml. The lysosomal localization of NeuAc accumulation in affected fibroblasts was confirmed by treatment of post-nuclear supernatant fractions with 0.5 mM Gly-Phe-beta-naphthylamide (20 min, 37 degrees C) prior to centrifugation, which resulted in the simultaneous loss of latency of Hex and free NeuAc, and their association with the soluble fraction on Percoll gradients. The results provide direct evidence for the accumulation of free NeuAc in a unique buoyant lysosomal fraction of affected fibroblasts.

Carbohydrate Metabolism, Inborn Errors↗

Relationship of prolonged pharmacologic serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1,500 grams or less.

The incidence of culture-proven neonatal sepsis and necrotizing enterocolitis (NEC) in preterm infants maintained at pharmacologic (mean 5.1 mg/dL +/- 1.45 SD) serum vitamin E levels for long periods was prospectively studied as part of a double-masked clinical trial of the effect of prophylactic vitamin E v placebo treatment on the development and course of retinopathy of prematurity (ROP). Within a few days of birth, 914 preterm infants were enrolled in the study; 545 (275 placebo-treated infants, 270 vitamin E-treated infants had birth weight of 1,500 g or less. A significant difference in incidence of neonatal sepsis (17 placebo-treated infants, 37 vitamin E-treated infants) and NEC (18 placebo-treated infants, 32 vitamin E-treated infants) was observed among infants who had been treated for eight or more days and who had developed neither sepsis nor NEC before that time. The association of vitamin E treatment with increased incidence of disease was much higher with sepsis than with NEC. The most likely reason for these observations is a pharmacologic serum vitamin E-related decrease in oxygen-dependent intracellular killing ability which results in a decreased resistance to infection in preterm infants. The data suggest that, if this occurs, it is clinically significant only in the more immature infants. In view of the known variability of absorption of oral vitamin E and the association between high serum vitamin E levels and increased incidence of sepsis and late-onset NEC reported here, it can be concluded that serum vitamin E levels must be monitored when supplemental vitamin E is administered to premature infants, especially those with birth weight 1,500 g or less. The risk-benefit ratio of long-term treatment using vitamin E at high serum levels should be clearly assessed.

Administration, Oral↗