Factors associated with non-completion of follow-up: 33-month latent tuberculous infection treatment trial.

SETTING: A post-hoc exploratory analysis of a randomized, open-label clinical trial that enrolled 8053 participants from the United States, Canada, Brazil, and Spain. OBJECTIVE: To assess factors associated with non-completion of study follow-up (NCF) in a 33-month latent tuberculous infection treatment trial, PREVENT TB. DESIGN: Participants were randomized to receive 3 months of weekly directly observed therapy vs. 9 months of daily self-administered therapy. NCF was defined as failing to be followed for at least 993 days (33 months) from enrollment. Possible factors associated with NCF were analyzed using univariate and multivariate regression via Cox proportional hazard model. RESULTS: Of 7061 adults selected for analysis, 841 (11.9%) did not complete study follow-up. Homelessness, young age, low education, history of incarceration, smoking, missing an early clinic visit, receiving isoniazid only, and male sex were significantly associated with NCF. Similar results were found in the North American region (United States and Canada) only. In Brazil and Spain, the only significant factor was missing an early clinic visit. CONCLUSIONS: Study subjects at higher risk for NCF were identified by characteristics known at enrollment or in early follow-up. Evaluation of follow-up in other trials might help determine whether the identified factors consistently correlate with retention.

Tackling the unknowns of short-course rifapentine-based treatment for active tuberculosis: a decision analysis.

BACKGROUND: Shorter treatment regimens for tuberculosis (TB) are deemed vital for advancing TB control. Murine studies have suggested potential new regimens; however, Phase II human studies of these drug combinations have not shown clear improvement in 2-month culture conversion over current therapy. Nevertheless, drugs such as rifapentine (RPT) may have additional sterilizing effects after 2 months that are difficult to measure in current Phase II studies. OBJECTIVES: To model potential bactericidal effects of RPT in a Phase III trial of a 4-month anti-tuberculosis regimen. METHODS: We developed a Markov model of anti-tuberculosis treatment to compare two regimens for treating TB: a 6-month standard (rifampin-based) treatment and a 4-month regimen using high-dose RPT. The primary outcome was the number of relapses. RESULTS: In the base-case scenario, standard therapy resulted in fewer relapses; improvement in 2-month culture conversion rates in the RPT arm did not change this result. However, while RPT has better sterilizing ability during months 3 and 4 (as observed in the mouse model), the 4-month regimen results in fewer relapses. CONCLUSIONS: Higher 2-month culture conversion rates are neither sufficient nor necessary for making a theoretical 4-month anti-tuberculosis treatment regimen advantageous.

Expanding tuberculosis case notification among marginalized groups in Bangladesh through peer sputum collection.

Case notification rates of tuberculosis (TB) in Bangladesh remain poor despite a high burden of disease. Peer sputum collection among underserved populations was implemented to expand case notification and to provide socially empowering roles in society for often excluded members of marginalized populations. Over the 55 months of the evaluation, 32 587 members of key populations were screened for TB, with 1587 smear-positive TB cases detected. Broadening TB services at human immunodeficiency virus drop-in centers using peer sputum collection to target high-risk populations for TB may be an effective way to increase TB case notification among key populations in Bangladesh.

Le taux de déclaration des cas de tuberculose (TB) au Bangladesh reste médiocre en dépit du lourd fardeau de la maladie. Le recueil de crachats par les pairs au sein des populations vulnérables a été mis en œuvre pour augmenter la déclaration des cas et également fournir des rôles socialement valorisants à des membres des populations marginales souvent exclus. Pendant 55 mois d'évaluation, 32 587 membres de ces populations ont bénéficié d'un dépistage de la TB, qui a permis de détecter 1587 cas de TB à frottis positif. L'expansion des services de TB dans les centres pour le virus d'immunodéficience humaine sans rendez-vous, utilisant le recueil de crachats par les pairs pour cibler les populations à haut risque de TB, peut être une façon efficace d'augmenter la déclaration des cas de TB parmi les populations les plus touchées au Bangladesh.

Las tasas de notificación de la tuberculosis (TB) en Bangladesh siguen siendo bajas pese a la alta carga de morbilidad por esta enfermedad. Se introdujo una medida de recogida de esputo por los pares en las poblaciones desatendidas, con el objeto de aumentar la notificación de casos y al mismo tiempo crear funciones de empoderamiento social en poblaciones marginadas, dirigidas a miembros de la comunidad que con frecuencia están excluidos. Durante los 55 meses de la evaluación, se investigó la TB en 32 587 miembros de poblaciones clave y se detectaron 1587 casos de TB con baciloscopia positiva. Una ampliación de los servicios de atención de la TB a los centros de encuentro y consulta de la infección por el virus de la inmunodeficiencia humana con aplicación de una estrategia de recogida de esputo por los pares y destinada a llegar a las poblaciones de alto riesgo de contraer la TB, sería una medida efectiva en aras de mejorar la notificación de los casos en las poblaciones clave de Bangladesh.

Sprint interval exercise elicits near maximal peak VO2 during repeated bouts with a rapid recovery within 2 minutes.

AIM: We investigated the cardiorespiratory response during acute sprint interval exercise (SIE; 4 x 30 sec maximal efforts, each separated by 4 min recovery) vs. continuous endurance exercise (CEE; 30 min) at 70% VO2max. METHODS: Oxygen consumption (VO2) and heart rate were measured in 8 males (age: 23±2.3 y, height: 181±6.4 cm, body mass: 78±8.6 kg, VO2max: 52±3.1 ml·kg-1·min-1, mean±SD). Pre-exercise diet was controlled. RESULTS AND CONCLUSION: Total VO2 was greater with CEE vs. SIE (87.6±13.1 vs. 35.1±4.4 L O2) with small differences (P=0.06) in average heart rates (CEE: 157±10 bpm vs. SIE: 149±6 bpm) and peak heart rates (CEE: 166±10 vs. SIE: 173±6; P=0.14). VO2 increased during the sprint bouts (53-72% of VO2max) and attained near maximal values (84-96%) in the immediate recovery period (within 20 sec). Thereafter a rapid decrease occurred so that at 2 min of recovery VO2 was ~1.5 L/min (~38% VO2max). During the remaining 2 min of recovery VO2 declined more slowly to ~1.3 L/min or ~33% of VO2max. Similar heart rate responses with CEE and SIE and a greater VO2 during SIE suggest increased muscle oxygen extraction with SIE, which might explain the greater peripheral adaptations, observed previously with sprint vs. continuous training. The potential value of shorter recovery durations to SIE needs to be examined.

Intermittent tuberculosis treatment for patients with isoniazid intolerance or drug resistance.

SETTING: Twenty tuberculosis (TB) clinics in the United States and Canada. OBJECTIVE: To evaluate the efficacy and safety of a 6-month intermittent regimen of rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB) in human immunodeficiency virus (HIV) negative patients with culture-confirmed pulmonary or extra-pulmonary tuberculosis and either isoniazid (INH) resistance or INH intolerance. DESIGN: Patients were enrolled in a single-arm clinical trial to receive intermittent dosing after at least 14 initial daily doses of RMP+PZA+EMB. Treatment was continued twice (BIW) or thrice weekly (TIW) per physician/patient preference for a total of 6 months, with 2 years of follow-up for relapse after treatment. RESULTS: From 1999 to 2004, 98 patients were enrolled, 78 with reported INH resistance and 20 with INH intolerance. BIW dosing was used in 77 and TIW in 21. Study treatment was completed in 73 (74%). Reasons for discontinuation were hepatic adverse events (n= 12), other adverse effects (n= 3) and other reasons (n= 10). Failure (n= 1) and relapse (n= 2) occurred in 3 (3.5%, 95%CI 1.2-9.8) of 86 patients eligible for efficacy analysis, all occurring in patients with cavitary, acid-fast bacilli smear-positive pulmonary TB. CONCLUSIONS: Intermittent RMP+PZA+EMB appears to be effective in HIV-negative patients, but the regimen is poorly tolerated, possibly due to the prolonged use of PZA. Alternative regimens of lower toxicity are needed.

Impaired superficial femoral artery vasodilation and leg blood flow in young obese women following an oral glucose tolerance test.

This study was designed to test the hypothesis that glucose ingestion following an overnight fast increases leg vascular conductance (LVCd) and superficial femoral artery (SFA) vasodilation in lean but not obese young women. Obese (23.5 ± 4.0 years, 84.7 ± 14.7 kg, 37.2% ± 6.4% fat; mean ± SD, n = 8) and lean (23.8 ± 2.4 years, 60.6 ± 4.0 kg, 22.3% ± 2.8% fat; n = 8) women arrived in the laboratory at 0830 h after a 12-h overnight fast for body composition (densitometry) assessment. Then, capillary blood glucose (BGlu), plasma insulin, heart rate, cardiac output, mean arterial pressure, leg blood flow (Doppler ultrasound), and LVCd were measured (after 15 min in the supine position), and at 30-min intervals for 2 h following glucose ingestion (75 g glucose load, 12.5% solution). Fasting BGlu concentration was not different between groups (obese = 5.1 ± 0.47 vs. lean = 4.9 ± 0.37 mmol·L(-1), p = 0.71) but 60, 90, and 120 min post ingestion BGlu was elevated (p ≤ 0.03) in the obese women. Insulin differences were not significant. Fasting LVCd was not different between groups (lean = 0.72 ± 0.49 vs. obese = 0.70 ± 0.19 mL·min(-1)·mm Hg(-1); p = 0.48); however, LVCd, as well as Δ in SFA diameter were significantly elevated (p ≤ 0.04) in the lean compared with the obese group at 60, 90, and 120 min postglucose ingestion (LVCd, peak lean = 1.4 ± 0.5 vs. peak obese = 0.8 ± 0.1 mL·min(-1)·mm Hg(-1); Δ in SFA, peak lean = 0.51 ± 0.30 vs. peak obese = 0.09 ± 0.45 mm). The reduced LVCd following glucose ingestion could contribute to impaired glucose tolerance. Further, the lack of SFA dilation may be evidence of impaired vascular insulin responsiveness in these obese young women.

Mortality before or during treatment among tuberculosis patients in North Carolina, 1993-2003.

SETTING: North Carolina, United States. OBJECTIVE: To investigate the demographic and behavioral risk factors associated with death among tuberculosis (TB) patients in North Carolina. DESIGN: Retrospective cohort of all TB patients reported in North Carolina, 1993-2003 (inclusive). A surveillance dataset based upon Report of Verified Case of Tuberculosis (RVCT) records was cross-linked with the National Death Index (NDI) to confirm date of death and capture additional deaths. RESULTS: Among 5311 TB patients, 181 died before initiation of TB treatment, and 540 died before completion of TB treatment. Increasing age, miliary/meningeal disease, and human immunodeficiency virus (HIV) infection were associated with increased risk of death before treatment, during early treatment (initial 8 weeks) and later in TB treatment. In addition to these factors, excess alcohol use (HR 1.62, 95%CI 1.13-2.32) and residence in a nursing home (HR 1.65, 95%CI 1.20-2.29) were associated with a significantly increased risk of death during the first 8 weeks of treatment. CONCLUSION: Many of the deaths in TB patients occurred in the most vulnerable populations, such as the elderly or those with HIV infection, and may be attributable to delayed diagnosis and poor functional status.

Missed opportunities for diagnosis of tuberculosis and human immunodeficiency virus co-infection in Moshi, Tanzania.

SETTING: A community-based voluntary counseling and testing (VCT) center in Moshi, Tanzania. OBJECTIVE: To compare rates of prior human immunodeficiency virus (HIV) testing among clients with and without previous tuberculosis (TB) treatment, and HIV seropositivity among those with and without current TB symptoms. DESIGN: Cross-sectional study of consecutive clients presenting for initial testing; sociodemographic and clinical data were collected via a structured questionnaire. HIV status was compared among clients with or without three or more TB-related symptoms: weight loss, fever, cough, hemoptysis or night sweats. RESULTS: Overall, 225 (3%) of 6583 VCT clients who responded to questions on previous TB treatment reported a history of TB, but only 34 (15%) reported previous HIV testing. This rate of HIV testing was not different from the rate among those clients without a history of TB (OR 0.77, P = 0.175). One hundred thirty-five (61%) clients with a history of TB were HIV-infected at VCT, compared with 17% of all clients. Of the total 6592 first-time testers who responded, 372 (6%) had at least three symptoms suggestive of TB at VCT. These symptoms were strongly associated with HIV seropositivity (OR 16.30, P < 0.001). CONCLUSION: Missed opportunities for HIV diagnosis at the time of TB treatment appear frequent in this population, underscoring the need for integration of TB and HIV diagnostic services.

Association of SLC11A1 with tuberculosis and interactions with NOS2A and TLR2 in African-Americans and Caucasians.

SETTING: Host defense factors may influence the development of active tuberculosis (TB). OBJECTIVE: To test variants in solute carrier family 11A, member 1 (SLC11A1), for an association with TB. METHODS: A mixed case-control study of TB cases, relatives or close contact controls, consisting of 474 African-Americans (243 families) and 381 Caucasians (192 families), examined 13 SLC11A1 polymorphisms for association with pulmonary TB using generalized estimating equations adjusting for age and sex. RESULTS: Two associations were observed in Caucasians (rs3731863, P = 0.03, and rs17221959, P = 0.04) and one in African-Americans (rs3731865, P = 0.05). Multilocus analyses between polymorphisms in SLC11A1 and 11 TB candidate genes detected interactions between SLC11A1 and inducible nitric oxide synthase (NOS2A) in Caucasians (rs3731863 [SLC11A1] x rs8073782 [NOS2A], P = 0.009; rs3731863 [SLC11A1] x rs17722851 [NOS2A], P = 0.007) and toll-like receptor 2 (TLR2) in African-Americans (rs3731865 [SLC11A1] x rs1816702, P = 0.005). CONCLUSIONS: No association was detected with 5'(GT)(n) promoter polymorphism previously associated with lower SLC11A1 expression, rs17235409 (D543N), or rs17235416 (3' TGTG insertion/deletion polymorphism). SLC11A1 polymorphism rs3731865 was associated with TB in African-Americans, consistent with previous findings in West Africans. These results suggest that variants in SLC11A1 increase susceptibility to pulmonary TB and interact with other variants that differ by race.

The value of end-of-treatment chest radiograph in predicting pulmonary tuberculosis relapse.

SETTING: Patients with cavitary pulmonary tuberculosis (TB) on baseline chest radiograph (CXR) who remain culture-positive after 8 weeks of treatment are at high risk of relapse. The role of end-of-treatment (EOT) CXR in predicting relapse is unclear. OBJECTIVE: To determine whether EOT CXR independently predicts TB relapse. DESIGN: We conducted a secondary analysis of a randomized trial of intermittent treatment using rifapentine in the continuation phase of TB treatment among 1004 human immunodeficiency virus seronegative adults with culture-proven pulmonary TB. RESULTS: Relapse occurred in 17.3% of subjects with persistent cavity on EOT CXR, in 7.6% of subjects with a cavity that resolved by EOT, and 2.5% (P=0.002 for trend) of subjects who never had a cavity. In multivariable analysis, patients with persistent cavity on EOT CXR were significantly more likely to relapse than patients with no cavity on baseline or 2-month CXR (hazard ratio [HR] 4.22, 95%CI 2.00-8.91), and were more likely to relapse than subjects whose early cavity had resolved by EOT CXR (HR 1.92, 95%CI 1.09-3.39). CONCLUSION: A persistent cavity after 6 months of TB treatment was independently associated with disease relapse after controlling for other variables. EOT CXR may help predict those likely to relapse.

Tuberculosis knowledge and attitudes among physicians who treat young children in North Carolina, USA.

SETTING: North Carolina, USA. OBJECTIVE: To understand physicians' knowledge and attitudes toward the treatment of young children with latent tuberculosis infection (LTBI) in a low-incidence region. DESIGN: Cross-sectional survey of 525 pediatricians and 525 family practitioners in North Carolina. RESULTS: Of 1050 surveys mailed, 149 (14%) were returned. In the previous year, 96% of responding physicians had treated children who had emigrated from a tuberculosis (TB) endemic country. During the last 2 years, 84% of physicians had not diagnosed any young children with TB disease, and 46% had not treated any young children with LTBI. Most (83%) physicians routinely placed tuberculin skin tests (TSTs), and 26% reported placing > 10 TSTs per month. Experience in treating children with LTBI was the only predictor of TB knowledge. Physicians were particularly confused about two issues: 1) TST among bacille Calmette-Guérin (BCG) vaccinated children and 2) treatment of young children with recent exposure to an adult with infectious TB. CONCLUSIONS: Knowledge of important issues related to management of LTBI in children aged < 5 years was limited among physicians in an area with relatively low TB incidence. Creative methods must be developed to help physicians in low-incidence areas to appropriately diagnose and treat LTBI among young children.

Antiretroviral therapy effects on genetic and morphologic end points in lymphocytes and sperm of men with human immunodeficiency virus infection.

Many human immunodeficiency virus (HIV)-infected persons receive prolonged treatment with DNA-reactive antiretroviral drugs. A prospective study was conducted of 26 HIV-infected men who provided samples before treatment and at multiple times after beginning treatment, to investigate effects of antiretrovirals on lymphocyte and sperm chromosomes and semen quality. Several antiretroviral regimens, all including a nucleoside component, were used. Lymphocyte metaphase analysis and sperm fluorescence in situ hybridization were used for cytogenetic studies. Semen analyses included conventional parameters (volume, concentration, viability, motility, and morphology). No significant effects on cytogenetic parameters, semen volume, or sperm concentration were detected. However, there were significant improvements in sperm motility for men with study entry CD4 cell counts >200 cells/mm(3), sperm morphology for men with entry CD4 cell counts < or =200 cells/mm(3), and the percentage of viable sperm in both groups. These findings suggest that nucleoside-containing antiretrovirals administered via recommended protocols do not induce chromosomal changes in lymphocytes or sperm but may produce improvements in semen quality.

Vertical transmission of multidrug-resistant human immunodeficiency virus type 1 (HIV-1) and continued evolution of drug resistance in an HIV-1-infected infant.

To confirm the vertical transmission of multidrug-resistant (MDR) human immunodeficiency virus type 1 (HIV-1) and to assess its impact on further evolution of drug-resistant virus in an infant, proviral DNA amplified from infected peripheral blood mononuclear cell cultures was sequenced to identify reverse transcriptase (RT) and protease (PR) mutations. The infant had proviral DNA with evidence of RT mutations (M41L, L74V, and T215Y) and 3 PR substitutions (K20R, M36I, and V82A). After delivery, the mother's proviral DNA had the same substitutions. Phylogenetic analyses of these HIV-1 RT and PR sequences indicated epidemiological linkage. Plasma drug susceptibility was determined by using a recombinant virus assay. Plasma HIV-1 obtained after the infant's birth demonstrated reduced susceptibility to zidovudine and ritonavir. Thus, vertical transmission of MDR HIV-1 was demonstrated in the setting of detectable maternal plasma viremia. Further accumulation of broad MDR in the infant's virus to 3 antiretroviral classes occurred, despite postnatal therapy.

Diabetes reduces right atrial beta-adrenergic signaling but not agonist stimulation of heart rate in swine.

This study assessed the effects of streptozotocin diabetes in swine on the heart rate response to beta-adrenergic stimulation the adenylyl cyclase signal transduction pathway. Diabetic animals (n = 9) were hyperglycemic compared to the control group (n = 10) (12.6 +/- 1.0 vs. 3.53 +/- 0.29 mM). There were no significant differences between the diabetic and nondiabetic groups in the heart rate response to isoproterenol, however, there was a significant reduction (14%) in beta-adrenergic receptor density in the right atrium in the diabetic (61 +/- 3 fmol/mg protein) versus the nondiabetic group (71 +/- 3) (P < 0.05). The content of guanosine triphosphate binding regulatory proteins (Gs and Gi) in the right atrium was not affected by diabetes, nor was adenylyl cyclase activity under unstimulated conditions or with receptor-dependent stimulation with isoproterenol. On the other hand, adenylyl cyclase activity was 34% lower when directly stimulated with forskolin, and it was reduced by 23% when stimulated through Gs with Gpp(NH)p. In conclusion, beta-adrenergic stimulation of heart rate with isoproteronol and the receptor-dependent signal transduction pathway remained intact in the right atrium of diabetic swine despite reduced beta-adrenergic receptor density, G-protein content, and direct stimulation of adenylyl cyclase activity.

Hospital management of tuberculosis in a region with a low incidence of tuberculosis and a high prevalence of nontuberculous mycobacteria.

We prospectively assessed the management of patients with suspected tuberculosis (TB) in an area with a high prevalence of nontuberculous mycobacteria (NTM) and a low incidence of TB. Clinicians' assessments were sensitive for TB but had poor predictive value. The acid-fast smear was a weak predictor of TB, owing to a high rate of isolation of NTM.

Antepartum or postpartum isoniazid treatment of latent tuberculosis infection.

OBJECTIVE: To compare health outcomes and costs of different strategies for treatment of latent tuberculosis infection in pregnancy. METHODS: Using a Markov decision-analysis model, the following three strategies were evaluated for treatment of latent tuberculosis infection in pregnancy, defined as positive tuberculin skin reaction of 10 mm or greater and negative chest radiograph: no treatment, antepartum isoniazid administration, in which women were given 300 mg of isoniazid with pyridoxine beginning at 20 weeks' gestation for 6 months; and postpartum isoniazid, in which women were given isoniazid and pyridoxine for 6 months after delivery. Sensitivity analyses were performed for a wide range of probability and cost estimates, and considered discount rates. RESULTS: Under base-case assumptions, the fewest cases of tuberculosis within the cohort occurred with antepartum treatment (1400 per 100,000) compared with no treatment (3300 per 100,000) or postpartum treatment (1800 per 100,000). Antepartum treatment resulted in a marginal increase in life expectancy due to the prevented cases of tuberculosis, despite more cases of isoniazid-related hepatitis and deaths, compared with no treatment or postpartum treatment. Antepartum treatment was the least expensive. Only if the case-fatality rate for tuberculosis was tenfold lower than the base-case and the risk of fatal hepatitis tenfold higher did antepartum treatment become the least advantageous strategy. CONCLUSION: Rather than delaying treatment until postpartum, consideration for antepartum treatment of latent tuberculosis during pregnancy should be given. If isoniazid is not administered antepartum, then efforts to improve postpartum compliance should be instituted, as either antepartum or postpartum treatment is better than no treatment.

Excessive use of vancomycin: a successful intervention strategy at an academic medical center.

The project goal was to decrease excessive vancomycin use. Interventions included an educational chart note the first day of therapy, followed by pharmacists discussing the need for continued therapy with patients' physicians. Empirical vancomycin use improved from 20% to 90% compliance with guidelines within 6 months of the intervention.

The use of a transscrotal testosterone delivery system in the treatment of patients with weight loss related to human immunodeficiency virus infection.

PURPOSE: Weight loss is a strong predictor of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. Men with acquired immunodeficiency syndrome (AIDS) lose body cell mass. Hypogonadism is also common. This study tested the efficacy of a testosterone transscrotal patch (6 mg/day) in improving body cell mass and treating hypogonadism in these patients. SUBJECTS AND METHODS: This multicenter, randomized, double-blinded, placebo-controlled trial was conducted from August 1995 to October 1996 in 133 men, 18 years of age and older, who had AIDS, 5% to 20% weight loss, and either a low morning serum total testosterone level (<400 ng/dL) or a low free testosterone level (<16 pg/mL). Outcomes included weight, body cell mass as measured using bioelectrical impedance analysis, quality of life, and morning measurements of serum testosterone and dihydrotestosterone levels, lymphocyte subsets, and HIV quantification. RESULTS: There were no significant differences in baseline weight, CD4 cell counts, or HIV serum viral quantification between treatment arms. Morning total and free testosterone levels increased in those treated with testosterone, but not with placebo. Following 12 weeks of treatment there were no differences (testosterone-placebo) in mean weight change (-0.3 kg [95% confidence interval (CI): -1.4 to 0.8]) or body cell mass (-0.2 kg [95% CI: -1.0 to 0.6]) in the two groups. There were also no changes in quality of life in either group. CONCLUSION: Hypogonadal men with AIDS and weight loss can achieve adequate morning serum sex hormone levels using a transscrotal testosterone patch. However, this system of replacement does not improve weight, body cell mass, or quality of life.

Clostridium septicum myonecrosis presenting as a parapharyngeal abscess in a patient with aplastic anemia.

The first reported case of Clostridium septicum myonecrosis in an adult with aplastic anemia is described. The patient presented with sepsis, a parapharyngeal abscess that necessitated emergent intubation, and severe intravascular hemolysis attributed to clostridial alpha-toxin production. Despite prompt recognition and treatment, the patient died of his infection. C. septicum myonecrosis should be considered in any immunocompromised patient with sepsis, especially when accompanied by evidence of multiple sites of tissue infection.

The reharvested central third of the patellar tendon. A histologic and biomechanical analysis.

We assessed the histologic, mechanical, and structural properties of the reharvested central-third patellar tendon in greyhounds. Twelve dogs had the central third of the patellar tendon (5 mm) removed with corresponding bone blocks from the patella and tibia; the remaining tendon defect was loosely closed. Six dogs were sacrificed at 6 months and six at 12 months, and the central third of the patellar tendon was harvested from both the operative and the contralateral control knees. Analysis of the structural changes in the tendons revealed a significant increase in thickness for reharvested tendons at both 6 and 12 months when compared with controls. The entire residual tendons were narrower at 6 months and were shorter at 12 months compared with controls. Mechanical testing showed that the average failure load, ultimate tensile strength, strain at failure, and average modulus for the reharvested central third of the patellar tendon were significantly less than that of controls at both 6 and 12 months. Analysis of collagen fiber size by electron microscopy revealed a significant increase in collagen fiber diameter at 6 months (135 +/- 41 nm versus 49 +/- 4 nm) but no difference between the operative limbs and controls at 12 months. The reharvested bone-patellar tendon-bone complex does not have the same properties as the primary patellar tendon graft up to 1 year after harvest in a canine model, and its use for revision cruciate ligament reconstruction must be carefully reexamined.