Comparison of patient and doctor responses to a total hip arthroplasty clinical evaluation questionnaire

BACKGROUND: Surgeons traditionally undertake a prospective evaluation of patients undergoing total hip arthroplasty in order to determine outcomes. The validity of doctor-derived data is questionable because of the potential for interobserver error, reporting bias, and differences between the perceptions of doctors and patients. Also, the use of doctor-derived data necessitates the use of costly outpatient services. Consequently, there are likely to be benefits associated with the use of patient-derived clinical evaluation data. However, few studies have focused on whether data obtained from the patient and doctor differ. METHODS: The agreement between patient and doctor responses on a sixteen-item total hip arthroplasty clinical evaluation questionnaire completed at more than 2900 clinical assessments was determined. Data from repeated assessments performed preoperatively and postoperatively enabled stratified analyses that were used to examine reasons for disagreement and factors influencing agreement. Agreement was measured with use of the kappa coefficient. RESULTS: For twelve of the sixteen items, the patient responses had acceptable agreement with the doctor responses. Some important differences between patient-derived and doctor-derived data were found. If the patient had other joint or health problems, had a revision total hip arthroplasty, or reported mild or moderate pain, there was a greater chance of reduced agreement on the pain items. Younger patients demonstrated better agreement with doctors than older patients did. CONCLUSIONS: Patients' perceptions of symptoms and outcomes after total hip arthroplasty are relatively similar to those of their doctor. There is minimum risk of misinterpreting outcomes data by replacing doctor-completed questionnaires with patient-completed questionnaires in uncomplicated total hip arthroplasty cases. For patients with comorbid joint problems or other health problems, and for those reporting substantial pain, direct physician involvement in the evaluation of pain is recommended. The selective use of patient-completed questionnaires has the potential to substantially reduce the costs of outcomes evaluation programs by minimizing doctor input. Pending revision of some of the items, the use of this patient-completed questionnaire is advocated.     

Identification of an ARS element and development of a high efficiency transformation system for Pichia guilliermondii

An Autonomously Replicating Sequence element adjacent to the RIB1 gene encoding GTP cyclohydrolase II of the yeast Pichia guilliermondii was identified by transformation experiments. Detailed sequence analysis unveiled two potential ARS elements located 5′ and 3′ of the RIB1 open reading frame. The chromosomal fragment containing the ARS-like sequence 3′ to the RIB1 structural gene, called PgARS, conferred high transformation frequencies of 10⁴–10⁵ transformants/μg of DNA to a pUC19-derived plasmid in P. guilliermondii. The PgARS element also conferred autonomous replication to hybrid plasmids in this host. Based on this element a series of Escherichia coli shuttle vectors for efficient transformation of the flavinogenic yeast P. guilliermondii was developed. Received: 22 September 1998 / 1 June 1999     

Obesity and Mental Illness: Implications for Cognitive Functioning

A priority research and clinical agenda is to identify determinants of cognitive impairment in individuals with neuropsychiatric disorders (NPD). The bidirectional association between NPD and cognitive performance has been reported to be mediated and/or moderated by obesity in a subset of individuals. Obesity can be conceptualized as a neurotoxic phenotype among individuals with NPD as evidenced by alterations in the structure and function of neural circuits and disseminated networks, diminished cognitive performance, and adverse effects on illness trajectory. The neurotoxic effect of obesity provides a rationale for screening, treating, and preventing obesity in neuropsychiatric populations. Research endeavors that aim to refine mediators and moderators of this association as well as novel strategies to reverse the injurious process of obesity on cognition are warranted.     

Reactive granular histiocytosis secondary to arthroplasty prosthesis: a novel reaction pattern

A reactive histiocytic infiltrate can be seen as an incidental finding in a lymph node biopsy from a patient with a history of joint arthroplasty. We report the case of a 74-year-old female who underwent surgical revision of a polyethylene-based right total knee prosthesis due to chronic wear. At the time of surgery, a soft tissue mass adjacent to the tibial prosthetic insert was noted and excised. Histopathologic examination revealed a sheet-like proliferation of large, histiocytoid cells within the subcutis and superficial fascia. The cells showed abundant eosinophilic, granular cytoplasm and small round bland nuclei. Immunohistochemical evaluation revealed the cells to be positive only for CD68. In addition, abundant PAS-positive cytoplasmic granules were found, and minute particles of polarizable material were noted intracellularly and scattered throughout the interstitium of the infiltrate. These findings were interpreted as consistent with a reactive, non-Langerhans cell histiocytosis secondary to the patient's polyethylene knee prosthesis. This finding appears to be a local correlate of the process previously described in regional lymph nodes as reactive granular histiocytosis. Dermatopathologists should be cognizant of this uncommon reaction pattern to avoid mistaking it for a neoplastic process.     

Distinct dendritic spine and nuclear phases of calcineurin activation after exposure to amyloid-β revealed by a novel fluorescence resonance energy transfer assay

Calcineurin (CaN) activation is critically involved in the regulation of spine morphology in response to oligomeric amyloid-β (Aβ) as well as in synaptic plasticity in normal memory, but no existing techniques can monitor the spatiotemporal pattern of CaN activity. Here, we use a spectral fluorescence resonance energy transfer approach to monitor CaN activation dynamics in real time with subcellular resolution. When oligomeric Aβ derived from Tg2576 murine transgenic neurons or human AD brains were applied to wild-type murine primary cortical neurons, we observe a dynamic progression of CaN activation within minutes, first in dendritic spines, and then in the cytoplasm and, in hours, in the nucleus. CaN activation in spines leads to rapid but reversible morphological changes in spines and in postsynaptic proteins; longer exposure leads to NFAT (nuclear factor of activated T-cells) translocation to the nucleus and frank spine loss. These results provide a framework for understanding the role of calcineurin in synaptic alterations associated with AD pathogenesis.     

Quantitative high-throughput screening for chemical toxicity in a population-based in vitro model

A shift in toxicity testing from in vivo to in vitro may efficiently prioritize compounds, reveal new mechanisms, and enable predictive modeling. Quantitative high-throughput screening (qHTS) is a major source of data for computational toxicology, and our goal in this study was to aid in the development of predictive in vitro models of chemical-induced toxicity, anchored on interindividual genetic variability. Eighty-one human lymphoblast cell lines from 27 Centre d'Etude du Polymorphisme Humain trios were exposed to 240 chemical substances (12 concentrations, 0.26nM-46.0μM) and evaluated for cytotoxicity and apoptosis. qHTS screening in the genetically defined population produced robust and reproducible results, which allowed for cross-compound, cross-assay, and cross-individual comparisons. Some compounds were cytotoxic to all cell types at similar concentrations, whereas others exhibited interindividual differences in cytotoxicity. Specifically, the qHTS in a population-based human in vitro model system has several unique aspects that are of utility for toxicity testing, chemical prioritization, and high-throughput risk assessment. First, standardized and high-quality concentration-response profiling, with reproducibility confirmed by comparison with previous experiments, enables prioritization of chemicals for variability in interindividual range in cytotoxicity. Second, genome-wide association analysis of cytotoxicity phenotypes allows exploration of the potential genetic determinants of interindividual variability in toxicity. Furthermore, highly significant associations identified through the analysis of population-level correlations between basal gene expression variability and chemical-induced toxicity suggest plausible mode of action hypotheses for follow-up analyses. We conclude that as the improved resolution of genetic profiling can now be matched with high-quality in vitro screening data, the evaluation of the toxicity pathways and the effects of genetic diversity are now feasible through the use of human lymphoblast cell lines.     

A history of early stent thrombosis is associated with prolonged clot lysis time

It has been demonstrated that formation of compact plasma fibrin clots resistant to plasmin-mediated lysis characterises patients following in-stent thrombosis (IST). The relationship between defective fibrinolysis, reflected as prolonged clot lysis time (CLT) and IST is unclear. We sought to investigate whether patients with acute and subacute IST have impaired fibrinolytic capacity. We studied 41 definite IST patients, including 15 with acute and 26 with subacute IST experienced 2-73 months prior to enrollment, versus 41 controls matched for demographics, cardiovascular risk factors, concomitant treatment and angiographic/stent parameters. CLT, reflecting lysis of a tissue factor-induced plasma clot by exogenous tissue plasminogen activator, together with plasminogen activator inhibitor-1 (PAI-1) antigen and activity, thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and activity, thrombomodulin (TM), plasminogen and α2-antiplasmin (α2AP) were measured. There were no inter-group differences in angiographic parameters, indication to the first PCI, culprit vessel or a type of stent. Patients with IST had 11% longer CLT (p=0.005) and 13% higher PAI-1 antigen (p=0.04) compared to controls. There were positive correlations in both groups between CLT and PAI-1 antigen and TAFI activity (all p<0.001). Multiple regression analysis showed that CLT (odds ratio [OR]=1.04 per 1 minute, 95% CI 1.01-1.08, p=0.02) and platelet count (OR=1.01 per 1,000/μl, 95% CI 1.00-1.02, p=0.034) were independent predictors of IST (R(2)=0.28, p<0.05). Concluding, impaired fibrinolytic potential, that is in part determined by plasma PAI-1 antigen and TAFI activity, characterises patients with a history of acute and subacute IST, which might help identify patients at higher risk of IST.