Solution phase synthesis of libraries of variably substituted olefin scaffolds: a library of allylic amines.

The synthesis of allylic amine libraries derived from olefin templates is described. The two-step, solution phase reaction sequence consists of amination of the template followed by Suzuki coupling and expedited purification via ion exchange chromatography. The methodology has been used to synthesize a 1344-member allylic amine library.

Levels of carbon dioxide in helmet systems used during orthopaedic operations.

The use of isolation helmets has gained popularity as a method of possible protection of the operating-room personnel from diseases that can be transmitted during operative procedures. However, the use of these systems has been associated with a variety of symptoms, including fatigue, diaphoresis, nausea, headache, and irritability. These symptoms have often been attributed to the mental stress of the operative procedure or the physical discomfort of the helmet. As far as we know, no manufacturers include the measured levels of carbon dioxide or the rate of air exchange of their helmet system. A possible common cause of discomfort with helmet systems is the level of carbon dioxide to which the person wearing the device is exposed. We measured the levels of carbon dioxide in four helmet systems from three different manufacturers during light exercise designed to approximate the exertion during an orthopaedic operation. All but one unit failed to meet the exposure limits recommended by the National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration regarding exposure to carbon dioxide. One unit, the Stackhouse Freedom Aire self-contained system, did meet these standards, but the levels of carbon dioxide in this helmet were more than 1000 per cent greater than the ambient levels in air (440 parts per million compared with 4939 parts per million). Isolation systems must be evaluated carefully not only for comfort but also for the physiological effects caused by exposure to elevated levels of carbon dioxide. Operating-room personnel who use such systems should be aware that many of the physical symptoms that they experience may be associated with elevated levels of carbon dioxide.

Arthroscopic-assisted outpatient anterior cruciate ligament reconstruction using the semitendinosus and gracilis tendons.

This study presents an average of 43-month results (range, 23 to 75 months) of 82 arthroscopically assisted, outpatient semitendinosus-gracilis anterior cruciate ligament reconstructions evaluated with the Cincinnati Knee Rating System. There were 44 acute and 38 chronic injuries. The results showed no significant effect of injury chronicity on all outcome variables except knee motion complications. Additionally, no significant difference was found between men and women in regards to outcome. At follow-up, 93% showed complete or partial graft function, 98% had a full range of knee motion, 83% had returned to sports with no problems, and 92% rated their knee condition as normal or very good. The mean overall point score (0 to 100 scale) for all patients was 92 +/- 10 points. All patients with chronic injuries showed improvement from their preoperative status, including 11 who had articular cartilage lesions. Complications were few; only five patients (6%) needed additional treatment for limitation of knee motion, and no patient had an increase in patellofemoral crepitus. We concluded that this procedure produced desirable results and that patients with long-standing functional limitations significantly improved and were able to return to an active lifestyle.

Combinatorial chemistry using polymer-supported reagents.

During the past several years, the field of combinatorial chemistry has expanded to include not only solid- and solution-phase methods for expedited compound synthesis, but also hybrid approaches that span these two extremes. In particular, polymer-supported reagents have emerged as useful combinatorial chemistry tools for the discovery and optimization of new pharmaceutical leads.

Arthroscopic reconstruction of the ACL with semitendinosus-gracilis autograft in skeletally immature adolescent patients.

It has been recommended that reconstruction of the anterior cruciate ligament (ACL) in skeletally immature patients should not violate the physeal plate of the distal femur or proximal tibia as growth irregularity might occur. Despite the lack of conclusive evidence that tendon transfers through growth areas cause growth irregularity, recent reports suggest that ligament reconstruction be performed in a nonisometric fashion to avoid violating the growth plate. Eight skeletally immature individuals underwent ligament reconstruction (average age: 14 years 9 months) and were reviewed retrospectively at an average of 32 months postsurgery. Surgery was performed using a hamstring tendon autograft through femoral and tibial tunnels (7 to 9 mm). Seven patients underwent scanograms at follow-up to confirm skeletal limb equality. All patients had at least 2 cm longitudinal growth after surgery. Stability tests were performed using both manual and KT-1000 arthrometer measurements. No clinically significant limb-length discrepancy or angular deformity was observed. Stability was excellent in five patients (< 3 mm side-to-side difference) and 8 mm in a patient with a repeat injury. Two patients presented with contralateral ACL-deficient knees. All eight patients were able to return to the same sport as before the injury. Modified Cincinnati Knee Rating scores revealed 100% excellent results in those four patients acutely reconstructed with average postoperative scores of 98 points. The four patients with chronic tears also exhibited average postoperative scores of 98 points. Ligament reconstruction using the semitendinosus and gracilis autograft can give excellent results in the skeletally immature individual. There appears to be minimal risk to the growth areas of the tibia or the femur at the knee. The graft can be safely passed through anatomically accurate bony drill holes in an arthroscopic fashion without apparent damage.

The use of high-throughput synthesis and purification in the preparation of a directed library of adrenergic agents.

A library of potential agonists and antagonists for adrenergic receptors was prepared using high-throughput solution-phase parallel synthesis. Traditional solution-phase reductive amination reactions followed by rapid purification by ion exchange chromatography yielded products with near-analytical purity. An array of ketones and amines, arranged in an 8 x 12 matrix, were combined to form 96 individual compounds.

Case report 808: Avulsion fracture of the greater trochanter.

The differential diagnosis of unexplained hip pain after trauma in patients with normal radiographs includes both soft tissue and bony abnormalities. We have presented a case of an isolated fracture of the greater trochanter in an adult with normal radiographs where the diagnosis was made by MRI.

Osteochondritis dissecans of the talus: a new technique for arthroscopic drilling.

Ankle arthroscopy is an effective procedure for the evaluation and management of osteochondritis dissecans of the talus. For active individuals with detached lesions, excision, curettage, and drilling are an effective treatment. The ability to drill arthroscopically significantly reduces the morbidity associated with open procedures. The use of an anterior cruciate ligament guide and the transmalleolar approach are techniques that have been advocated for the drilling of defects on the posteromedial aspect of the talar dome. However, we describe a new technique using the meniscal repair instrumentation that permits accurate arthroscopic localization and drilling of osteochondral lesions; no transmalleolar portal is required.

Meniscal allografts.

Loss of the meniscus has been proved to be associated with increased joint pressures, mechanical changes, and ultimately hyaline cartilage degradation. Since the first arthritic changes following meniscectomy were appreciated, attempts have been made to alter and reverse the joint deterioration that occurs after removal of the knee fibrocartilage. Replacement of the fibrocartilage with either a prosthetic or biologic implant appears to be the only method of restoring normal joint anatomy. By inserting a meniscus substitute for the removed meniscus, the development of joint pathology should be avoided. This article focuses on the procedure of allogenic implants. Allogenic meniscal implants have been performed in humans for over 8 years. Recent clinical work has shown a rapid increase in the number of implants in the last 3 years with clinical review only now being presented. At present, the orthopedic surgeon has available cryopreserved, fresh-frozen, or frozen and irradiated tissue. Although much work has been performed in the animal with fresh-frozen tissue, the newly appreciated risk of disease transmission may require that all future implants be secondarily sterilized. Regardless of the type of implant, the early results of cell viability studies appear the same. Allogenic implants sustain new cellular ingrowth from the host and the DNA is replaced with host DNA. The ultimate success of this operation is not whether allogenic collagen can be transplanted into a host knee, but whether this tissue can be made to function and to preserve hyaline cartilage. Available data suggest that the technique being used to transplant the meniscus does not preserve normal meniscus function. These menisci may not function as they did in the donor. Additionally, few surgical techniques have been tested mechanically to compare meniscus function after transplantation. For these reasons, although transplant surgery for the meniscus remains an exciting and encouraging procedure to save the knee in a person who has had a total meniscectomy, the operation is currently being limited to those involved in study groups and investigational protocols. The long-term follow-up is at present limited or nonexistent. Objective parameters for evaluating posttransplant meniscus function are only now being collected and reviewed. Meniscal transplantation remains a cautiously optimistic treatment for the future.

EGR3, a novel member of the Egr family of genes encoding immediate-early transcription factors.

We have previously described two cellular immediate-early genes, Egr-1 (mouse) and EGR2 (human) that encode zinc finger proteins. Here we report the characterization of a new member of the Egr family referred to as EGR3 (human). This cDNA clone was isolated using low stringency hybridization with the zinc finger domain of Egr-1. The EGR3 cDNA sequence predicts a 387 amino acid (a.a.) protein containing three Cys2-His2 zinc fingers nearly identical to those of Egr-1 and EGR2. This similarity has a functional consequence: EGR3 can activate transcription of a CAT gene linked to the sequence CGCCCCCGC, a cis element which is a target for Egr-1 and EGR2. We show that EGR3 is an immediate-early growth response gene induced by mitogenic stimulation of rodent and human fibroblasts and a monkey kidney epithelial cell line. The EGR3 gene has a single intron and maps to chromosome 8 at bands p21-23.

Mechanical properties of primate vascularized vs. nonvascularized patellar tendon grafts; changes over time.

Mechanical properties of patellar tendon autografts used to replace the anterior cruciate ligament (ACL) in the cynomolgus monkey were measured at four time periods up to 1 year. The ACL was replaced in each knee with the medial half of the patellar tendon: as a vascularized graft (VG) on one side and as a nonvascularized or free graft (FG) on the other. Postoperative care consisted of 4 weeks of cast immobilization at 30 degrees flexion followed by unrestricted activity in a large cage. Both grafts showed low stiffness and maximum force at 7 weeks (24% and 16% of ACL control values, respectively), increasing to 57% of control ACL stiffness and 39% of control maximum force by 1 year. Corresponding material properties, modulus and maximum stress, also increased over time, but at 1 year were only 34% and 26% of ACL values, respectively. The results indicate that retaining vascularity does not prevent significant reduction in graft properties that occur postoperatively, nor does it accelerate the return in strength and stiffness. Tissue stiffness, which returns earlier than maximum force and joint anteroposterior (AP) force displacement data, should be routinely reported in any healing study. Finally, in studies of this kind, the large variation in the results makes sampling only one or two animals from each time period unreliable.

The use of computerized thermography in the evaluation of non-traumatic anterior knee pain.

Computerized thermography was used to evaluate eight patients with the complaint of non-traumatic anterior knee pain. Computerized thermograms were recorded before and after subjects performed a specific rehabilitation program. Thermographic imaging was then repeated 4 weeks to 8 weeks after the initial thermogram. Among the subject group, thermal asymmetries were noted in the involved knees, but a specific abnormal thermal pattern could not be recognized. Changes in temperature and thermal patterns after exercise and over time were consistent within each subject, but were not consistent between subjects. Thermal asymmetries did not appear to resolve over time. It is felt that the pathology investigated by this study may involve many etiologies, therefore making it difficult to establish a single abnormal thermal pattern with regard to non-traumatic anterior knee pain.

Superior dislocation of the patella with interlocking osteophytes.

Superior dislocation of the patella with interlocking osteophytes was only once found roentgenologically documented. Such a dislocation occurs without tendon rupture, and can occur with a hyperextension force. Reduction is easily accomplished by manipulation of the patella without anesthesia. Full active motion is present post-reduction. This entity should not be confused with vertical dislocations of the patella.

Syntheses, analgetic activity, and physical dependence capacity of 5-phenyl-6,7-benzomorphan derivatives.

The synthesis, analgetic activity, and physical dependence capacity of a large number of 5-phenyl-6,7-benzomorphan derivatives are described. Observations made during the Stevens' rearrangement of 1-benzyl-1-methyl-delta 3-piperidinium salt derivatives (V) under various conditions are discussed. The absolute configuration of the 9-demethyl series and the 2'-deoxy series is established by comparison of their ORD and CD spectra with those of 49, whose absolute configuration was previously established by X-ray crystallography. A convenient synthesis of 3H-labeled phenols using 3H3PO4 is described, as well as the preparation of 14C-labeled compounds by conventional methods.