Thirty-six of 44 patients (82%) who underwent ACL reconstruction using freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts were evaluated at least 2 years postoperatively. A detailed subjective evaluation using the Lysholm scale was recorded as well as a functional evaluation using the Tegner activity scale. All of the patients received a detailed physical examination that included testing with the KT-1000 ligament arthrometer and the Cybex dynamometer. Complete chart reviews and radiographic evaluations were also obtained. Only 17 patients were considered to be functionally successful and performing at their desired activity level. The average KT-1000 showed a side-to-side difference of 5.9 mm at 30 pounds for the successful group and 7.9 mm for those who had functional failure. The Lysholm scores were 91.6/100 versus 61.1/100 in the failures. Eight patients (22%) at repeat surgery were noted to have complete dissolution of the graft. Large femoral cysts were noted radiographically in all of these patients. It was concluded that freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts have a high failure rate and cannot be recommended for ACL reconstruction.

We performed a prospective, randomized study to evaluate the use of injected lidocaine as an anesthetic for closed reduction of acute anterior shoulder dislocations. Thirty consecutive patients who presented at the emergency department with acute anterior shoulder dislocations were randomly placed in one of two groups. One group received an intraarticular injection of 20 ml of 1% lidocaine and the other group, intravenous injections of morphine sulfate and midazolam. The groups were compared regarding time of reduction maneuver, difficulty of reduction, subjective pain, complications, and total time spent in the emergency department. The lidocaine provided adequate anesthesia and secondary relief of muscle spasm in 15 of 15 (100%) patients. When compared with the intravenous sedation group, the lidocaine group showed no statistically significant difference in time for reduction maneuver, difficulty of reduction, or subjective pain. The lidocaine group had no complications and had a statistically significant shorter emergency department visit when compared with the intravenous sedation group (mean, 78 minutes versus 186 minutes; P = 0.004). Lidocaine provides excellent anesthesia for patients with uncomplicated anterior shoulder dislocations and can be very beneficial when sedation is contraindicated. Lidocaine injections also proved to be cost effective in our institution, reducing total costs by as much as 62%.

Twenty-eight goats underwent ACL reconstruction with freeze-dried bone-patellar tendon-bone allografts in one knee, the opposite knee serving as a control. One group of 16 knees was evaluated, in groups of four, at 6, 12, 26, and 52 weeks by histologic and vascular injection techniques. The other group of 12 knees was evaluated in two groups of six at 26 and 52 weeks by morphological and biomechanical techniques of analysis. Within the first 12 weeks these allografts were revascularized; in the first 26 weeks they had matured to resemble normal connective tissue. Graft stiffness was 29% of the control value and maximum force to failure was 43% of the control value. The results of this study indicated that freeze-dried bone-patellar tendon-bone allografts are biomechanically and biologically similar to patellar tendon autografts.

Despite major advances in early detection and prognosis, chemotherapy resistance is a major hurdle in the battle against breast cancer. Identifying predictive markers and understanding the mechanisms are key steps to overcoming chemoresistance. Methylation-controlled J protein (MCJ, also known as DNAJC15) is a negative regulator of mitochondrial respiration and has been associated with chemotherapeutic drug sensitivity in cancer cell lines. Here we show, in a retrospective study of a large cohort of breast cancer patients, that low MCJ expression in breast tumors predicts high risk of relapse in patients treated with chemotherapy; however, MCJ expression does not correlate with response to endocrine therapy. In a prospective study in breast cancer patients undergoing neoadjuvant therapy, low MCJ expression also correlates with poor clinical response to chemotherapy and decreased disease-free survival. Using MCJ-deficient mice, we demonstrate that lack of MCJ is sufficient to induce mammary tumor chemoresistance in vivo. Thus, loss of expression of this endogenous mitochondrial modulator in breast cancer promotes the development of chemoresistance.

IgA1 proteases (IgA1P) from diverse pathogenic bacteria specifically cleave human immunoglobulin A1 (IgA1) at the hinge region, thereby thwarting protective host immune responses. Streptococcus pneumoniae (S. pneumoniae) IgA1P shares no sequence conservation with serine or cysteine types of IgA1Ps or other known proteins, other than a conserved HExxH Zn-binding motif (1604-1608) found in metalloproteases. We have developed a novel expression system to produce the mature S. pneumoniae IgA1P and we have discovered that this form is both attached to the bacterial cell surface and released in its full form. Our data demonstrate that the S. pneumoniae IgA1P comprises two distinct regions that associate to form an active metalloprotease, the first such example of a metalloprotease that can be split in vitro and recombined to form an active enzyme. By capitalizing on this novel domain architecture, we show that the N-terminal region of S. pneumoniae IgA1P comprises the primary binding region for IgA1, although the C-terminal region of S. pneumoniae IgA1P is necessary for cleavage of IgA1. Our findings lend insight into the protein domain architecture of the S. pneumoniae IgA1P and function of this important virulence factor for S. pneumoniae infection.