Bilateral, asynchronous, apophyseal fractures in the pelvis and proximal femur.
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Biomedical subjects
Publications and source records attributed to J S Williams.
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Endoscopic (single-incision) anterior cruciate ligament (ACL) reconstruction with bone patellar tendon bone can usually be secured with interference screws on the femur and tibia. Infrequently, patella alta, which results in a longer tendinous component of the graft construct, can result in construct mismatch, resulting in a large portion of the tibial bone plug extruding from the tibial tunnel, requiring graft fixation with staples or a suture/screw and post technique. This study investigated the hypothesis that initial graft fixation could be enhanced if the bone plug was removed and press fit into the tibial tunnel and then secured with an interference screw in the scenario of graft construct mismatch. Initial biomechanical fixation strengths of bovine patellar tendon were compared using a screw and post suture fixation compared with a free bone plug, which was removed from the graft and sandwiched along with the soft tissue with an interference screw. Twenty-eight bovine knees were randomly divided into two groups. Graft fixation was performed with a free bone plug excised from the tibial tubercle portion of the bone tendon bone construct. Fixation was achieved with a cannulated 9-mm x 20-mm interference screw. Fixation was performed in group 2 patients with a Krackow suture of no. 5 Ticron secured over a screw and post. An Instron materials testing system was used and loading rates at 1 mm/sec until failure was performed. Statistically significant differences were noted for load to failure and stiffness (P < .001). Group 1 specimens' mean maximum load to failure was 669 N (range, 511 to 819 N), whereas the load to failure for group 2 patients was 374 N (range, 266 to 491 N). Group 1 stiffness was 90 N/mm (range, 50 to 122 N/m) compared with a mean stiffness of 24 N/m (range, 16 to 33 N/m) for group 2 knees. In our bovine model, free bone block interference fixation was stronger and stiffer than fixation using sutures tied over a post. This fixation method of securing a soft tissue graft with an interference screw warrants further clinical investigation and may offer an improvement to the alternative of suture/post fixation.
Trauma accounts for nearly half of pediatric deaths in the United States. We reviewed all pediatric trauma-related deaths that occurred over a 5-year period at two Georgia trauma centers to determine the number of trauma deaths in children, mechanism of injury, cause of death, and compliance with safety standards. Of the 69 fatalities, 31 were caused by motor vehicle accidents. Twenty-five of these victims (81%) were unrestrained; 17 were 4 years old or less, and only 1 of them was restrained in a car seat. Pedestrian versus vehicle accidents resulted in 19 deaths, 10 of the victims being 4 years old or less. Bicycle versus vehicle accidents resulted in 4 deaths, 2 of them due to closed head injury; none of the victims wore headgear. All-terrain vehicle accidents resulted in 2 deaths from massive head injury; neither victim wore a helmet. One death occurred from bicycle handlebar injury; 12 deaths resulted from causes other than vehicle accidents. Major causes of pediatric fatalities were motor vehicle accidents (45%), pedestrian-vehicle accidents (28%), and bicycle accidents (6%). This study indicates that when safety measures such as restraint systems, helmets, or proper supervision are ignored, children may die as a result of trauma.
Two clinical lots of alum-adsorbed SPf66 vaccine produced in the United States were evaluated in separate, open-label, Phase I clinical trials involving 15 healthy, malaria-naive, 18-45-year old men and women. Subjects received 2 mg doses subcutaneously in alternate arms at 0, one, and six months. Safety was assessed by monitoring local and systemic reactions and laboratory parameters. The most common side effects were erythema and local tenderness at the site of injection, which increased in frequency with subsequent doses of vaccine. These local reactions were considered mild and resolved within 24-48 hr. Eleven of 14 volunteers who received all three doses of vaccine seroconverted by enzyme-linked immunosorbent assay. The distribution of high, medium, and low nonresponders was comparable with that seen in trials of Colombian-produced vaccine. One high responder developed antibodies reactive with asexual stage parasite antigens by immunofluorescence and immunoblot. The results indicated that at full adult doses, SPf66 of U.S. origin is mildly reactogenic and induces immune responses similar to those reported for SPf66 of Colombian origin.
Meniscal and nonosseous anterior cruciate ligament (ACL) injuries are being recognized in children and adolescents more frequently. This increase appears to be the result of better diagnostic skills, newer imaging techniques, and the ever-increasing physical demands of organized youth sports. We retrospectively reviewed all cases of knee arthroscopy performed at Brown University School of Medicine from August 1991 to April 1994 in patients < or = 15 years. Of the 24 patients with suspected meniscal or nonosseous ACL injuries based on history and physical examination, 18 (75%) were confirmed at arthroscopy. Fifty-six percent of the patients with nonosseous ACL tears had coexistent meniscal lesions. Twenty-one percent of the meniscal tears were peripheral and showed evidence of spontaneous healing at time of arthroscopy. Seventeen of these patients underwent preoperative magnetic resonance imaging (MRI). Four of the five patients with lateral meniscal tears, all three of the patients with medial meniscal tears, and both of the patients with ACL tears were identified correctly by MRI. This study suggests that a history and physical examination consistent with a meniscal or nonosseous ACL injury will be confirmed by arthroscopy in up to three quarters of adolescent patients. Therefore, the use of MRI should be reserved for those patients in whom the clinical findings are still in question after a careful history and physical examination has been completed.
Here we report the nucleotide sequence of the canine interleukin-2 (IL-2)-encoding cDNA. Cloning of the canine IL-2 cDNA was achieved by the polymerase chain reaction employing, as a template, a cDNA derived from mitogen-stimulated canine splenic lymphocyte mRNA. The deduced amino acid (aa) sequence of canine IL-2 consists of 155 aa and displays 84% sequence similarity to human IL-2.
The X gene product encoded by the hepatitis B virus, termed pX, is a promiscuous transactivator of a variety of viral and cellular genes under the control of diverse cis-acting elements. Although pX does not appear to directly bind DNA, pX-responsive elements include the NF-kappa B, AP-1, and CRE (cAMP response element) sites. Direct protein-protein interactions occur between viral pX and the CRE-binding transcription factors CREB and ATF. Here we examine the mechanism of the protein-protein interactions occurring between CREB and pX by using recombinant proteins and in vitro DNA-binding assays. We demonstrate that pX interacts with the basic region-leucine zipper domain of CREB but not with the DNA-binding domain of the yeast transactivator protein Gal4. The interaction between CREB and pX increases the affinity of CREB for the CRE site by an order of magnitude, although pX does not alter the rate of CREB dimerization. Methylation interference footprinting reveals differences between the CREB DNA and CREB-pX DNA complexes. These experiments demonstrate that pX titers the way CREB interacts with the CRE DNA and suggest that the basic, DNA-binding region of CREB is the target of pX. Transfection assays in PC12 cells with the CREB-dependent somatostatin promoter demonstrate a nearly 15-fold transcriptional induction after forskolin stimulation in the presence of pX. These results support the significance of the CREB-pX protein-protein interactions in vivo.
Deep vein thrombosis (DVT) with subsequent pulmonary emboli (PE) is the most life-threatening complication of knee arthroscopy. Although the incidence of clinically diagnosed DVT after arthroscopy is low, clinical examination is less sensitive and specific than other diagnostic modalities for the detection of venous clot. This study used compression ultrasound to prospectively evaluate patients before and after arthroscopic surgery for the presence of DVT. Preoperatively, patients were screened for DVT risk factors. Eighty-five patients completed the study. Three asymptomatic "silent" DVTs were identified, for an incidence of 3.5%. There was no statistically significant difference between those with and without risk factors for the development of DVT.
Complications of patellar-tendon allograft for anterior cruciate ligament (ACL) reconstruction in ACL-deficient patients have focused on disease transmission, strength, survivorship, technique, and processing to decrease antigenicity. Little has been described in regard to intrinsic complications of patellar-tendon allograft. This article discusses our experience with a damaged patellar-tendon allograft that was abnormally long and had a large osseous intratendinous mass. Based on this experience, we make recommendations on evaluating and procuring patellar-tendon allografts that will help orthopaedic surgeons avoid intrinsic patellar-tendon allograft complications.
Nursing home staff members frequently screen residents for competence, but the ability to assess competence has received limited attention. This study compared staff members' competence assessments with residents' (N = 100) mental status, measured by the Short Portable Mental Status Questionnaire (SPMSQ), and examined information used by staff to evaluate residents' competence. Staffers' evaluation of competence was significantly correlated with resident SPMSQ score. Staffers used information about orientation, alertness, and verbal function, with little consideration of decision making ability and mental status.
Our objective was to determine the prevalence of poisonous snakebite victims admitted to a regional trauma center in Southeastern Georgia over a 10-year period, as well as the type of snake, grade of envenomation, treatment administered, morbidity and mortality, and outcome. Records of patients admitted to the center for snakebite from a 24-county catchment area during the 10-year period (January 1984 to January 1994) were retroactively reviewed. Sixty-three (63) bites in 62 victims of venomous snakebites were treated. The snake distribution was rattlesnake: 19 (30%), copperhead: 18 (29%), cottonmouth moccasin: 8 (12%), unknown: 18 (29%). Envenomation grades were Grade I: 20 (32%), Grade II: 24 (38%), Grade III: 10 (16%), and Grade IV: 9 (14%). Fourteen of 19 (74%) Grades III and IV envenomations were from rattlesnakes. Antivenin was used in all Grade IV and half of the Grade III envenomations. Antivenin was administered within 3 hours of injury in all but one case. Five patients had surgery. Two patients (both Grade I) developed anaphylaxes from antivenin given before hospitalization. All patients recovered. An average of 6 snakebites were treated each year. Expeditious transport, attention to the type of snake inflicting the bite, and judicious use of antivenin will result in a favorable outcome for the snakebite victim.
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The cAMP-dependent protein kinase (PKA) phosphorylates CREB327/341 at a single serine residue, Ser119/133, respectively. Phosphorylation at this site creates the sequence motif SXXXS(P), a consensus site of the glycogen synthase kinase-3 (GSK-3) enzyme (Fiol, C.J., Mahrenholz, A.M., Wang, Y., Roeske, R.W., and Roach, P.J. (1987) J. Biol. Chem. 262, 14042-14048). We examined the phosphorylation of CREB at the SXXXS(P) consensus site and its role in CREB transactivation to cAMP induction. Neither isoform of the GSK-3 enzyme (GSK-3 alpha or beta) utilizes CREB as its substrate unless CREB is already phosphorylated at Ser119/133. A 13-amino acid peptide containing the sequence surrounding Ser119/133 was phosphorylated by GSK-3, at Ser115/129, only after the primary phosphorylation of the peptide by PKA (at Ser119/133), suggesting that Ser115/129 is a GSK-3 phosphoacceptor site. Mutant CREB327/341 proteins containing Ser-->Ala substitutions confirmed Ser115/129 as the only GSK-3 phosphorylation site. Transfection assays of wild type and mutant Gal4-CREB fusion proteins in PC12 cells demonstrated that Ser-->Ala substitution of residue 129 of CREB341 impairs the transcriptional response to cAMP induction. Analogous mutation in CREB327 results in 70% decrease in its transactivation response to cAMP. In undifferentiated F9 cells, which are refractory to cAMP induction, transfected GSK-3 beta kinase induces a 60-fold increase in cyclic AMP response element-dependent transcription, mediated via the endogenous CREB protein. We propose that the hierarchical phosphorylation at the PKA and GSK-3 sites of CREB are essential for cAMP control of CREB.
Intrinsic DNA curvature has previously been implicated in the condensation of satellite DNA in chromatin. In this article, electrophoretic methods and computer programs for predicting DNA structure from nucleotide sequence were used to determine if curvature is a conserved feature of satellite DNA. The results revealed that satellite sequences display wide variation in magnitude of intrinsic bending. Less than half of the satellites examined were strongly bent when compared with control DNA. However, a conserved pattern of bending was seen in all 57 satellite sequences that were studied. The pattern consisted of repeating units of two 50-60-base pair bending elements which were separated by a 20-30-base pair region of low curvature. This pattern resembles qualitatively the bending of DNA in the nucleosome where the helix is folded approximately two turns around the histone octomer with the turns interrupted by a less bent segment in the center of the particle. The distance between successive pairs of bending elements was also similar to the average spacing of nucleosomes in chromatin. Thus, the conserved structures could play some role in the positioning of nucleosomes along satellite chromatin. In order to strengthen the correlation between DNA structure and nucleosome positioning, sequences were examined which have been shown to position nucleosomes at single major sites. This analysis revealed a conserved pattern of DNA structure resembling the two peak units seen in satellites. In addition, the nucleotide sequence patterns responsible for the conserved patterns of bending were similar in both satellite and nucleosome positioning DNA. Likewise, nucleotide sequence patterns that are thought to direct the rotational orientation of DNA in the nucleosome were similar in both sequence sets. These results are considered in terms of a general model for the role of DNA bending and nucleotide sequence in the control of nucleosome positioning and chromatin condensation in eukaryotes.
A 5-year retrospective study of 530 motor vehicle fatalities revealed 105 aortic injuries occurring in 90 victims. These were reviewed to determine the injury patterns, circumstances, and mechanisms involved. In addition, the survival time, the driver's age and sex, the time of day of the accident, and the blood alcohol level were considered. The aortic injuries consisted of 61 transections and 44 tears (13% were multiple). Sixty-five percent of the injuries were located in the proximal descending aorta (66% of these were transections), 14% were in the ascending aorta and arch (33% of these were transections), 12% were in the distal descending aorta (more than 1 cm distal to the subclavian artery) (46% of these were transections), and 9% were in the abdominal aorta (56% of these were transections). Associated injuries consisted of multiple rib fractures (78%), liver lacerations (61%), head injuries (42%), first rib fractures (42%), splenic lacerations (36%), heart lacerations (34%), sternal fractures (28%), cervical spine fractures (26%), and thoracic spine fractures (20%). Death occurred within 1 hour in 94% and within 24 hours in 99%. The impact was head-on in 62% of the accidents. The victim was the driver 74% of the time and male in 77% of the cases, and the blood alcohol level exceeded 0.1 mg/dL in 43%. Most aortic disruptions were complete transections of the proximal descending aorta, associated with serious injury to the thorax, and occurred in head-on collisions. Findings support a compression and upward thrust of the heart as a mechanism responsible for the aortic disruption.
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