Factors influencing wear and osteolysis in press-fit condylar modular total knee replacements

The purpose of this study was to determine the factors influencing wear and osteolysis in patients who have had total knee arthroplasty with the Press-Fit Condylar modular system. Two-thousand ninety-one primary total knee replacements in 1737 patients were done using the Press-Fit Condylar system at three centers. Radiographic and manufacturing data were obtained for 2016 of the 2091 implants (96.4%). For the 1287 of 2016 knees (64%) with more than 5 years of followup, the prevalence of wear-related failure was 8.3%. The 13-year survivorship for all patients was 82.6%. Cox hazards analysis revealed five variables that were correlated with wear-related failure: patient age, patient gender, polyethylene sheet vendor, polyethylene finishing method, and polyethylene shelf age. We were unable to identify one factor as the defining reason for these wear-related failures. The multiple changes in manufacturing methods during the life of this implant may have precluded such a determination. These results may be specific to inserts sterilized in air with gamma irradiation and should not be generalized to current manufacturing techniques. This study emphasizes the potential deleterious effects that small changes in the manufacturing process may have on the outcome of a prosthesis with an initially favorable survivorship.     

Naturally occurring amino acid polymorphisms in human immunodeficiency virus type 1 (HIV-1) Gag p7(NC) and the C-cleavage site impact Gag-Pol processing by HIV-1 protease

Human immunodeficiency virus type 1 (HIV-1) protease activity is targeted at nine cleavage sites comprising different amino acid sequences in the viral Gag-Pol polyprotein. Amino acid polymorphisms in protease and in regions of Gag, particularly p7(NC) and the C-cleavage site between p2 and p7(NC), occur in natural variants of HIV-1 within infected patients. Studies were designed to examine the role of natural polymorphisms in protease and to identify determinants in Gag that modulate protease processing activity. Closely related Gag-Pol regions from an HIV-1-infected mother and two children were evaluated for processing in an inducible expression system, for protease activity on cleavage-site analogues, and for impact on replication by recombinant viruses. Gag-Pol regions displayed one of three processing phenotypes based on the appearance of Gag intermediates and accumulation of mature p24(CA). Gag-Pol regions that were processed rapidly to produce p24(CA) resulted in high-level replication by recombinant viruses, while slow-processing Gag-Pol variants resulted in recombinant viruses that replicated with reduced kinetics in both T cell lines and peripheral blood mononuclear cells. Direct impact by Gag sequences on processing by protease was assessed by construction of chimeric Gag-Pol regions and by site-directed mutagenesis. Optimal protease activity occurred when Gag and Pol regions were derived from the same gag-pol allele. Heterologous Gag regions generally diminished rates and extent of protease processing. Natural polymorphisms in novel positions in p7(NC) and the C-cleavage site have a dominant effect on protease processing activity. Accumulation of Gag products after processing at the C site appears to delay subsequent cleavage and production of mature p24(CA).     

Implementing a Web-based content management system

The Children's Hospital of Philadelphia transformed its web site to enhance patient satisfaction and attract new patients, as well as meet the needs of clinicians and the hospital's business plans. They accomplished this by implementing a content management system that would allow content creation and updating to be delegated to appropriate department staffers, thereby eliminating bottlenecks and unnecessary steps and ensuring that the web site receives fresh content much more quickly.     

The effectiveness of very short scales for depression screening in elderly medical patients

OBJECTIVE: To compare very short scales for screening for depression with longer, widely used scales. METHODS: Eighty-seven patients over the age of 60 who were admitted to rehabilitation wards or were attending a day rehabilitation facility at a British teaching hospital were screened for depression using the 1-item mental health inventory, and the 4-item, 15-item and 30-item geriatric depression scales. The sensitivity, specificity, and areas under receiver operating characteristic curves were compared, with the diagnostic criteria for research of ICD-10 providing the criterion diagnosis of depressive episode. RESULTS: All the scales had comparable sensitivity (82.4-100%), specificity (60.0-71.4%), and positive predictive values (33.3-42.9%). Comparison of receiver operating characteristic curves for each scale showed no statistically significant difference between them (range 0.80-0.88). CONCLUSIONS: The very short scales performed just as well as the widely used longer screening scales in this population. They are worthy of further examination in elderly populations at risk of depression, and may be particularly suitable for older adults due to their brevity and ease of use.     

Prenatal HIV prevention practices in a low seroprevalence state.

The purpose of this study was to build understanding of prenatal HIV counseling and testing practices in low seroprevalence states. Responses from a 1998 population-based survey of Kentucky prenatal care providers (67% response; 312 analyzed) were compared with findings from patient focus groups. Sixty-two percent of clinicians said they routinely counsel prenatal patients with risk factors, but only 46% routinely counsel patients without risk factors. The proportions routinely offering HIV testing to patients with and without risk factors were 94% and 84%, respectively. Prenatal patients identified "fear of a positive test result" as the major barrier to test acceptance. This fear was fueled by lack of knowledge regarding the benefits of early detection. The study concludes that achieving universal prenatal HIV testing will require new strategies, such as the distribution of a standardized protocol, that address clinicians' concerns about "time burdens" without depriving patients of the opportunity to receive individualized counseling.     

3,4-二氯苯丙烯酰另丁胺对大鼠脑缺血-再灌注损伤的影响

目的：研究新的桂皮酰胺类衍生物,３－４二氯苯丙烯酰另丁胺（ＡＥＤ８８０１）对大鼠脑缺血／再灌注损伤的影响。方法：采用Ｐｕｌｓｉｎｅｌｌｉ四血管阻断大鼠脑缺血／再灌注模型,观察了ＡＥＤ８８０１对脑组织中水含量、氨基到含量、６－ｋｅｔｏ－ＰＧＦ１α和ＴＸＢ２含量,以及二者之比值的影响。结果：一ＡＥＤ８８０１能够降低脑缺血／再灌注大鼠所引起的脑水含量增加。二采用氨基酸自动分析仪进行检测,发现脑缺血／再灌     

Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted but reside in the cytosol of squamous carcinoma cells

An elevation in the circulating level of the squamous-cell carcinoma antigen (SCCA) can be a poor prognostic indicator in certain types of squamous-cell cancers. Total SCCA in the circulation comprises 2 nearly identical, approximately 45 kDa proteins, SCCA1 and SCCA2. Both proteins are members of the high-molecular weight serine proteinase inhibitor (serpin) family with SCCA1 paradoxically inhibiting lysosomal cysteine proteinases and SCCA2 inhibiting chymotrypsin-like serine proteinases. Although SCCA1 and SCCA2 are detected in the cytoplasm of normal squamous epithelial cells, neither serpin is detected normally in the serum. Thus, their presence in the circulation at relatively high concentrations suggests that malignant epithelial cells are re-directing serpin activity to the fluid phase via an active secretory process. Because serpins typically inhibit their targets by binding at 1:1 stoichiometry, a change in the distribution pattern of SCCA1 and SCCA2 (i.e., intracellular to extracellular) could indicate the need of tumor cells to neutralize harmful extracellular proteinases. The purpose of our study was to determine experimentally the fate of SCCA1 and SCCA2 in squamous carcinoma cells. Using subcellular fractionation, SCCA-green fluorescent fusion protein expression and confocal microscopy, SCCA1 and SCCA2 were found exclusively in the cytosol and were not associated with nuclei, mitochondria, lysosomes, microtubules, actin or the Golgi. In contrast to previous reports, metabolic labeling and pulse-chase experiments showed that neither non-stimulated nor TNFalpha/PMA-stimulated squamous carcinoma cells appreciably secreted these ov-serpins into the medium. Collectively, these data suggest that the major site of SCCA1 and SCCA2 inhibitory activity remains within the cytosol and that their presence in the sera of patients with advanced squamous-cell carcinomas may be due to their passive release into the circulation.     

The effects of increased dose of exercise-based therapies to enhance motor recovery after stroke: a systematic review and meta-analysis

Background  

Exercise-based therapy is known to enhance motor recovery after stroke but the most appropriate amount, i.e. the dose, of therapy is unknown. To determine the strength of current evidence for provision of a higher dose of the same types of exercise-based therapy to enhance motor recovery after stroke.