Mark F. Brady

Congenital Trypanosoma cruzi Transmission in Santa Cruz, Bolivia

BACKGROUND We conducted a study of congenital Trypanosoma cruzi infection in Santa Cruz, Bolivia. Our objective was to apply new tools to identify weak points in current screening algorithms, and find ways to improve them. METHODS Women presenting for delivery were screened by rapid and conventional serological tests. For infants of infected mothers, blood specimens obtained on days 0, 7, 21, 30, 90, 180, and 270 were concentrated and examined microscopically; serological tests were performed for the day 90, 180, and 270 specimens. Maternal and infant specimens, including umbilical tissue, were tested by polymerase chain reaction (PCR) targeting the kinetoplast minicircle and by quantitative PCR. RESULTS Of 530 women, 154 (29%) were seropositive. Ten infants had congenital T. cruzi infection. Only 4 infants had positive results of microscopy evaluation in the first month, and none had positive cord blood microscopy results. PCR results were positive for 6 (67%) of 9 cord blood and 7 (87.5%) of 8 umbilical tissue specimens. PCR-positive women were more likely to transmit T. cruzi than were seropositive women with negative PCR results (P < .05). Parasite loads determined by quantitative PCR were higher for mothers of infected infants than for seropositive mothers of uninfected infants P < .01). Despite intensive efforts, only 58% of at-risk infants had a month 9 specimen collected. CONCLUSIONS On the basis of the low sensitivity of microscopy in cord blood and high rate of loss to follow-up, we estimate that current screening programs miss one-half of all infected infants. Molecular techniques may improve early detection.

Corticosteroids Reduce Postoperative Morbidity After Third Molar Surgery: A Systematic Review and Meta-Analysis

PURPOSE The purpose of this study was to apply meta-analytical methods to measure the effect of corticosteroids (CS) on edema, trismus, and pain at early and late postoperative periods after third molar (M3) removal. MATERIALS AND METHODS A systematic search of the literature was carried out to identify eligible articles. The primary predictor variable was perioperative CS exposure (yes or no). The 3 outcome variables were edema, trismus, and pain assessed during the early (1-3 days) and late (>3 days) postoperative time periods. Standardized mean differences (SMD) for edema and weighted mean differences (WMD) for trismus and pain were pooled across studies. Differences between the 2 treatment groups were assessed using random effects models and metaregressions for both early and late postoperative assessments. RESULTS Twelve trials met the inclusion criteria. Subjects receiving CS had significantly less edema during both early (SMD, 1.4; 95% confidence interval [CI], 0.6, 2.2; P < .001) and late (SMD, 1.1; 95% CI, 0.1, 2.0; P = .03) time periods after surgery and less trismus than controls during the early and late postoperative periods (early WMD, 4.1 mm; 95% CI, 2.8 mm, 5.5 mm; P < .001; late WMD, 2.7 mm; 95% CI, 0.8 mm, 4.6 mm; P = .005). Average pain levels were not significantly different between the 2 groups (early WMD, 0.4 visual analog scale [VAS]; 95% CI, -0.04 VAS, 0.9 VAS; P = .07; late WMD, 0.5 VAS; 95% CI, -0.6 VAS, 1.5 VAS; P = .4). CONCLUSIONS The findings of this study suggest that perioperative administration of corticosteroids produces a mild to moderate reduction in edema and improvement in range of motion after M3 removal.

Effects of Initial Graft Tension on the Tibiofemoral Compressive Forces and Joint Position After Anterior Cruciate Ligament Reconstruction

Background The initial tension applied to an anterior cruciate ligament graft at the time of fixation modulates knee motion and the tibiofemoral compressive loads. Purpose To establish the relationships between initial graft tension, tibiofemoral compressive force, and the neutral tibiofemoral position in the cadaveric knee. Study Design Controlled laboratory study. Methods The tibiofemoral compressive forces and joint positions were determined in the anterior cruciate ligament-intact knee at 0°, 20°, and 90° of knee flexion. The anterior cruciate ligament was excised and reconstructed with a patellar tendon graft using graft tensions of 1, 15, 30, 60, and 90 N applied at 0°, 20°, and 90° of knee flexion. The compressive forces and neutral positions were compared between initial tension conditions and the anterior cruciate ligament-intact knee. Results Increasing initial graft tension increased the tibiofemoral compressive forces. The forces in the medial compartment were 1.8 times those in the lateral compartment. The compressive forces were dependent on the knee angle at which the tension was applied. The greatest compressive forces occurred when the graft was tensioned with the knee in extension. An increase in initial graft tension caused the tibia to rotate externally compared with the anterior cruciate ligament-intact knee (1.5° and 7.7° of external rotation when tensioned to 90 N at 0° and 90° of knee flexion, respectively). Increases in initial graft tension also caused a significant posterior translation of the tibia relative to the femur (0.9 and 5.3 mm of posterior translation when tensioned to 90 N at 0° and 90° of knee flexion, respectively). Conclusion Different initial graft tension protocols produced predictable changes in the tibiofemoral compressive forces and joint positions. Clinical Relevance The tibiofemoral compressive force and neutral joint position were best replicated with a low graft tension (1-15 N) when using a patellar tendon graft.

Microscopic observation drug susceptibility assay for tuberculosis screening before isoniazid preventive therapy in HIV-infected persons

BACKGROUND Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in persons infected with human immunodeficiency virus (HIV), but currently used screening strategies have poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in individuals suspected of having TB. This study compared the efficacy, effectiveness, and speed of the microscopic observation drug susceptibility (MODS) assay with currently used strategies for TB screening before IPT in HIV-infected persons. METHODS A total of 471 HIV-infected IPT candidates at 3 hospitals in Lima, Peru, were enrolled in a prospective comparison of TB screening strategies, including laboratory, clinical, and radiographic assessments. RESULTS Of 435 patients who provided 2 sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS culture, 22 (5.1%) by Lowenstein-Jensen culture, and 7 (1.6%) by smear. Of patients with any positive microbiological test result, a MODS culture was positive in 96% by 14 days and 100% by 21 days. The MODS culture simultaneously detected multidrug-resistant TB in 2 patients. Screening strategies involving combinations of clinical assessment, chest radiograph, and sputum smear were less effective than 2 liquid TB cultures in accurately diagnosing and excluding TB (P<.01). Screening strategies that included nonculture tests had poor sensitivity and specificity. CONCLUSIONS MODS culture identified and reliably excluded cases of pulmonary TB more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. Streamlining of the ruling out of TB through the use of liquid culture-based strategies could help facilitate the massive up-scaling of IPT required to reduce HIV and TB morbidity and mortality.

The MODS method for diagnosis of tuberculosis and multidrug resistant tuberculosis.

Patients with active pulmonary tuberculosis (TB) infect 10-15 other persons per year, making diagnosing active TB essential to both curing the patient and preventing new infections. Furthermore, the emergence of multidrug resistant tuberculosis (MDRTB) means that detection of drug resistance is necessary for stopping the spread of drug-resistant strains. The microscopic-observation drug-susceptibility (MODS) assay is a low-cost, low-tech tool for high-performance detection of TB and MDRTB. The MODS assay is based on three principles: 1) mycobacterium tuberculosis (MTB) grows faster in liquid media than on solid media 2) microscopic MTB growth can be detected earlier in liquid media than waiting for the macroscopic appearance of colonies on solid media, and that growth is characteristic of MTB, allowing it to be distinguished from atypical mycobacteria or fungal or bacterial contamination 3) the drugs isoniazid and rifampicin can be incorporated into the MODS assay to allow for simultaneous direct detection of MDRTB, obviating the need for subculture to perform an indirect drug susceptibility test. Competing current diagnostics are hampered by low sensitivity with sputum smear, long delays until diagnosis with solid media culture, prohibitively high cost with existing liquid media culture methods, and the need to do subculture for indirect drug susceptibility testing to detect MDRTB. In contrast, the non-proprietary MODS method has a high sensitivity for TB and MDRTB, is a relatively rapid culture method, provides simultaneous drug susceptibility testing for MDRTB, and is accessible to resource-limited settings at just under

Frictional Properties of Hartley Guinea Pig Knees With and Without Proteolytic Disruption of the Articular Surfaces

3 for testing for TB and MDRTB.