Citations

Purpose We tested the hypothesis that the preimplantation mechanical properties of BioCleanse‐treated bone–patellar tendon–bone (BPTB) allografts are not significantly different from those of untreated specimens. Methods For this controlled laboratory study, specimens were harvested as central third or hemi‐BPTB units from both knees of 17 cadaveric tissue donors (11 men and 6 women) aged 19 to 88 years. Donor‐matched specimens (20 per group) were randomly assigned to either BioCleanse‐treated or untreated control groups. Specimens were subjected to 25 minutes of pretensioning at 89 N and then cyclically loaded under longitudinal tension between 50 N and 250 N for 1,000 cycles at 1 Hz, followed by ramp to failure at 50 mm/min. Results No statistically significant difference was found between untreated and BioCleanse‐treated specimens in stiffness (235.3 ± 37.6 N/mm v 222.3 ± 53.4 N/mm, P = .37), cyclic creep (0.38 ± 0.42 mm v 0.40 ± 0.26 mm, P = .81), maximum force (1,685.7 ± 471.6 N v 1,807.0 ± 657.8 N, P = .47), or ultimate stress (29.0 ± 9.8 MPa v 29.0 ± 12.8 MPa, P = .98). Conclusions The preimplantation mechanical properties of BPTB allografts treated with BioCleanse are not significantly different from those of untreated controls. Clinical Relevance This laboratory study compares the biomechanical properties of chemically treated allografts, which are currently being used in anterior cruciate ligament reconstruction, with those of nontreated fresh‐frozen allografts.

Purpose Our purpose was to evaluate the results of transphyseal anterior cruciate ligament (ACL) reconstruction with medial hamstring autograft in skeletally immature patients. Methods We reviewed the records of all skeletally immature patients who underwent transphyseal ACL reconstruction with medial hamstring autograft between 1988 and 2002 at our institution. Inclusion criteria were age less than 15 years for male patients, age less than 14 years for female patients, and radiographic evidence of wide open physes. We identified 16 patients (11 male and 5 female). All underwent preoperative and postoperative clinical evaluation (physical examination and modified Lysholm and International Knee Documentation Committee scores), and knee radiographs. Each patient was followed up until skeletal maturity was confirmed, with a mean clinical follow‐up of 41.1 months (range, 24 to 112 months). Results The mean time from ACL injury to reconstruction was 5.6 months (range, 0.7 to 26.9 months). During the preoperative time period, 4 patients (25%) developed meniscal tears that were not visualized on the index magnetic resonance imaging scans. At last follow‐up, the mean leg length discrepancy measured 0.62 cm (range, 0.2 to 1.5 cm), and clinical or radiographic evidence of malalignment was not present in any of the patients. In 1 patient a symptomatic 1.5‐cm limb overgrowth developed, which was treated with an internal shoe lift. At follow up, the mean modified Lysholm score was 98.8 (range, 94 to 100), and the mean International Knee Documentation Committee score was 89.9 (range, 73.6 to 94.3). Of the patients, 7 (43.8%) underwent a reoperation, and 2 suffered traumatic graft disruption. Conclusions ACL reconstruction with a medial hamstring autograft via a transphyseal technique yields satisfactory clinical results in skeletally immature patients. No new meniscal tears were identified after ACL reconstruction, and most patients (87.5%) returned to their previous level of activity. The rate of reoperation was high (43.8%). Physeal growth arrest did not occur. Level of Evidence Level IV, therapeutic case series.

Background— Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role. Methods and Results— Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180±71 versus 455±184 seconds; peak oxygen consumption 9.0±3.4 versus 14.4±3.4 mL · kg −1 · min −1 ; both P <0.001). At matched low-level workload, HFpEF subjects displayed ≈40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all P <0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups. Conclusions— HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.

AbstractPurpose: To determine the recommended starting doses and pharmacokinetics of irinotecan in cancer patients with impaired liver function treated on a weekly schedule.Experimental Design: Patients with solid tumors who had impaired liver function were enrolled into four groups based on baseline serum total bilirubin and aspartate aminotransferase (AST)/alanine aminotransferase (ALT): Group 1 (n = 19): total bilirubin 1.5 to 3.0 × institutional upper limit of normal (IULN) and ALT/AST ≤5.0 × IULN; Group 2 (n = 7): total bilirubin 3.1 to 5.0 × IULN and ALT/AST ≤5.0 × IULN; Group 3 (n = 6): total bilirubin ≤1.5 × IULN and ALT/AST 5.1 to 20.0 × IULN; Group 4 (n = 10): total bilirubin 1.5 to 3.0 × IULN and ALT/AST 5.1 to 20.0 × IULN. Irinotecan was given as a 90-minute i.v. infusion weekly for the first 4 weeks in each 6-week cycle at starting doses which escalated from 40 to as much as 75 mg/m2. After the first treatment, doses were adjusted based on individual patient toxicities. Starting doses for patients with hepatic dysfunction were derived from the maximum tolerated doses noted in the four hepatic dysfunction groups.Results: Forty-two patients were treated. Among the most frequent adverse events were neutropenia (41%, grades 3/4), diarrhea (15%, grades 3/4), nausea (10%, grade 3), and vomiting (5%, grades 3/4). Two patients died from drug-induced neutropenic sepsis. Two patients had objective tumor responses (complete response, liver metastases from unknown primary; partial response, colon cancer). Hepatic dysfunction reduced irinotecan clearance while increasing relative exposure to the active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). SN-38 exposures in patients receiving doses of 40 to 75 mg/m2 were comparable to exposures in patients with normal liver function treated with a starting dose of 125 mg/m2.Conclusions: Irinotecan starting doses that seem to be safe for hepatically impaired patients treated with the weekly schedule are 60, 50, 60, and 40 mg/m2 for groups 1 to 4, respectively. At these starting doses, exposure to SN-38 and the adverse event profile are similar to that observed in patients with normal liver function and antitumor activity can be observed.

Background— Vasoreactivity tests are fundamental in evaluating pulmonary arterial hypertension (PAH). Mutations of the transforming growth factor-β type II receptor gene, BMPR2 , predispose to the development of pulmonary hypertension and may alter the response to vasodilators. Previous investigations have not examined the relationship of BMPR2 mutations to vasoreactivity. Methods and Results— We identified 133 consecutive unrelated patients with either idiopathic or familial PAH. Sixty-six patients were excluded because we lacked either DNA samples (n=18) or complete data from a vasoreactivity test (n=48). The remaining 67 patients were screened for BMPR2 DNA sequence variations, and specific variations were confirmed by gene sequencing. The vasoreactivity of patients with nonsynonymous BMPR2 variations was compared with that of patients without nonsynonymous BMPR2 variations. We found nonsynonymous BMPR2 variations in 27 of 67 patients with idiopathic (n=16 of 52) or familial (n=11 of 15) PAH. Vasoreactivity was identified in 3.7% of 27 patients with nonsynonymous BMPR2 variations and in 35% of 40 patients without nonsynonymous BMPR2 variations ( P =0.003). Five of the 27 nonsynonymous variations occur commonly in healthy individuals. None of the remaining 22 patients with BMPR2 variations demonstrated vasoreactivity, and the analysis remained unchanged when we assumed that nonsynonymous BMPR2 variations were present in all 15 patients with familial PAH. Conclusions— Patients with familial or idiopathic PAH and nonsynonymous BMPR2 variations are unlikely to demonstrate vasoreactivity. Further trials are required to determine whether long-term therapy can be directed by tests for BMPR2 variations.

Abstract To assess the cost-effectiveness of interventions to prevent osteoporosis, it is necessary to estimate total health care expenditures for the treatment of osteoporotic fractures. Resources utilized for the treatment of many diseases can be estimated from secondary databases using relevant diagnosis codes, but such codes do not indicate which fractures are osteoporotic in nature. Therefore, a panel of experts was convened to make judgments about the probabilities that fractures of different types might be related to osteoporosis according to patient age, gender, and race. A three-round Delphi process was applied to estimate the proportion of fractures related to osteoporosis (i.e., the osteoporosis attribution probabilities) in 72 categories comprised of four specific fracture types (hip, spine, forearm, all other sites combined) stratified by three age groups (45–64 years, 65–84 years, 85 years and older), three racial groups (white, black, all others), and both genders (female, male). It was estimated that at least 90% of all hip and spine fractures among elderly white women should be attributed to osteoporosis. Much smaller proportions of the other fractures were attributed to osteoporosis. Regardless of fracture type, attribution probabilities were less for men than women and generally less for non-whites than whites. These probabilities will be used to estimate the total direct medical costs associated with osteoporosis-related fractures in the United States.

Abstract Arthroscopic debridement is a reliable and effective treatment for knee arthritis in appropriately selected patients. Debridement may include lavage, loose body removal, partial meniscectomy, and/or chondroplasty. Patient selection criteria include acute effusion, well localized joint line tenderness, or catching or locking, often associated with a specific mechanism of injury, patients with imaging studies confirming loose bodies, patients with earlier stages of degenerative joint disease, and patients with realistic understanding that the goal of arthroscopy is to diminish pain and improve function and not to cure their arthritis. Surgeons are cautioned, in patients with an osteoarthritic knee, MRI may be overly sensitive and inadequately specific with regard to correlation between pathologic findings (with the exception of loose bodies) and predictably treatable disease. In conclusion, the authors cite the Arthroscopy Association of North America Position Statement on Osteoarthritis: “There is…a sub‐group of patients with knee arthritis that can be significantly helped with appropriate arthroscopic surgery.”

Abstract Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate. Objectives To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin. Methods A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000–2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-γ treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed. Results Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5–11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7–9.2) and HRCT response by 4.9 times (95% CI, 1.9–13.0). Culture response was 1.5 times (95% CI, 1.1–2.2) higher for older subjects and 2.2 times (95% CI, 1.0–4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1–5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7–11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0–2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times. Conclusions TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.