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Biomedical subjects

K Bennett

Publications and source records attributed to K Bennett.

12 recordsLinked to original sources

EDucation and eXercise for gluteal tendinopathy in an Irish context (EDX-Ireland): findings from the LEAP-Ireland feasibility randomised controlled trial.

OBJECTIVE: To assess feasibility of a randomised controlled trial (RCT) investigating effectiveness of 6 sessions of an EDucation and eXercise intervention delivered over 8 weeks (EDX-Ireland) for gluteal tendinopathy, against usual care. EDX-Ireland was modified from a 14-session EDucation and eXercise intervention (EDX), delivered over 8 weeks, previously evaluated in an Australian RCT. DESIGN: Feasibility parallel RCT. METHODS: Participants were randomly assigned to physiotherapist-led EDX-Ireland or usual care. EDX-Ireland comprised 6 sessions of education, hip abductor strengthening and functional loading over 8 weeks, supported by a home exercise programme. Primary outcomes included success of different recruitment strategies and recruitment/retention rates. Secondary outcomes measured global rating of change and other clinical outcomes. Descriptive statistics (percentage, mean, standard deviations and 95% confidence intervals (CI)) are presented. RESULTS: Of 323 individuals who expressed interest in study participation, 119 completed physical examination screening, and 65 met criteria and consented to participate (recruitment rate 55%). Sixty-five people (89% women; mean age 53.1 ± 9.3 years), were randomised to EDX-Ireland (n = 32) or usual care (n = 33). Eighty-three percent (n = 54) were recruited via social media/community, 3% (n = 2) from general practitioners and 14% (n = 9) from orthopaedic/rheumatology. Retention was 92% (95% CI 82-97%, n = 60) at 8-weeks, and 89% (95% CI 79-96%, n = 58) at 3-months. Feasibility thresholds were met. Effect size estimates indicate that 134 participants would be required for a future RCT. CONCLUSION: Pre-defined recruitment and retention thresholds were met, indicating that a RCT evaluating 6 sessions of physiotherapist-delivered education and exercise against usual care for gluteal tendinopathy is feasible. TRIAL REGISTRATION: Clinicaltrials.gov (NCT05516563).

Humans

Quality-of-life assessment: patient compliance with questionnaire completion.

BACKGROUND: Previous investigators have found that compliance with quality-of-life data collection on cancer clinical trials is poor. There is general belief that collecting complete quality-of-life data is at present an unachievable goal. PURPOSE: We assessed the completeness of quality-of-life data collection on trials instituted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), since incorporation of quality-of-life outcomes into trials became mandatory for the group. METHODS: Data from three NCIC CTG trials in which quality of life was a study end point were examined to determine the extent to which protocol specifications were met with respect to questionnaire completion. Two of the studies examined adjuvant therapies, and one examined anti-emetics. In two trials, the quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer was used; in the other, the Breast Cancer Chemotherapy Questionnaire. RESULTS: Patient compliance with questionnaire completion was unexpectedly high: More than 95% of the scheduled questionnaires were returned, and more than 99% of the questions were answered. CONCLUSIONS: We attribute this success to a comprehensive set of measures taken to enhance compliance on these studies. Which of these measures was most contributory requires further investigation, as does the issue of whether similar results can be obtained in other circumstances. IMPLICATIONS: It seems that the commonly held belief that quality-of-life data cannot be successfully collected in multicenter cancer trials is incorrect.

Clinical Trials as Topic

Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E.

Proteolytic degradation (processing) of antigen by antigen-presenting cells is a major regulatory step in the activation of a T lymphocyte immune response. However, the enzymes responsible for antigen processing remain largely undefined. In this study we show that cathepsin E, and not the ubiquitous lysosomal cathepsin D, is the major aspartic proteinase in a murine antigen-presenting cell line, A20. This enzyme is localized to a non-lysosomal compartment of the endosomal system in these cells. Functional studies using a highly specific inhibitor of cathepsin E show that this enzyme is essential for the processing of ovalbumin by this cell line. Thus, cathepsin E, whose function was hitherto unknown, may play a major role in antigen processing.

Animals

cDNA cloning and sequence analysis of beta ig-h3, a novel gene induced in a human adenocarcinoma cell line after treatment with transforming growth factor-beta.

Transforming growth factor-beta (TGF-beta) is capable of affecting the proliferation of many cell types. To identify novel genes whose protein products may mediate cellular responses to this factor, a cDNA library was made from mRNA isolated from a human lung adenocarcinoma cell line (A549) that had been treated for 3 days with TGF-beta. The library was screened by differential hybridization and a cDNA clone, beta ig-h3, was isolated. This gene was induced up to 20-fold in A549 cells after 2 days of treatment with TGF-beta 1. It was also induced in several other cell lines, including PC-3 and H2981. DNA sequence analysis of beta ig-h3 indicated that it encoded a novel protein, beta IG-H3, of 683 amino acids, which contained an amino-terminal secretory sequence and a carboxy-terminal Arg-Gly-Asp (RGD) sequence that can serve as a ligand recognition site for several integrins. beta IG-H3 also contained short amino acid regions homologous to similar regions in Drosophila fasciclin-I and four homologous internal domains, which can be folded into a potential bivalent structure and could act as a bridge between cells expressing the appropriate ligand. beta ig-h3 RNA was detected in several cell lines and tissues. COS cells transfected with plasmids encoding beta IG-H3 secreted a major 68-kD protein that was detected by immunoblotting using antipeptide antibodies. Since beta ig-h3 is induced in several cell lines whose proliferation is affected by TGF-beta 1, it may be involved in mediating some of the signals of this multifunctional growth modulator.

Adenocarcinoma

Extending community health nursing services. The Student Learning Center.

Faced with scarce resources, the Visiting Nurse Association of Omaha (VNA), Bishop Clarkson College, Creighton University, and University of Nebraska Medical Center collaborated to maintain services. Baccalaureate students learned to deliver community health nursing while serving a population in need of these services, but not coverable by funding sources. The Student Learning Center established by the VNA enabled 254 students to provide 5,035 home visits to families without funding sources.

Community Health Nursing

Methodologic challenges in the development of utility measures of health-related quality of life in rheumatoid arthritis.

Utility measures of health-related quality-of-life (HRQL) are unique in that they focus on patient preferences for alternative health conditions and combine benefit and toxicity into one number. This paper addresses the application of utility measurement techniques to assess HRQL in rheumatoid arthritis (RA). More specifically, the measurement issues and empirical evaluation strategies relevant to establishing the usefulness of utility measures in clinical trials and "n of 1" studies in RA are presented. First, utilities are reviewed within the context of RA and the other measures of benefit and toxicity currently in use. Second, the key methodologic challenges relevant to the development of HRQL measures of RA treatment impact are identified. Finally, a new utility instrument suitable for use in both parallel group and "n of 1" drug trials in RA is presented. The work described also addresses the interpretation of utility values and hence their acceptability to clinicians, researchers and policy makers and may aid initiatives to establish HRQL as one of the criteria for approval by federal drug regulatory agencies. Given that patient preferences constitute a central concept within the framework of HRQL, further empirical evaluation of utility measures of preference is fundamental to improving the HRQL measurement tool-kit.

Arthritis, Rheumatoid

Effect of hydrocortisone on cell morphology in C6 cells.

Hydrocortisone has been found to induce cell spreading in rat glial C6 cells by 24 hours after its addition. This spreading phenomenon is correlated with an increase in the fraction of the peripheral cytoplasm occupied by microfilaments. Cytochalasin B causes disorganization of microfilaments in the peripheral cytoplasm of the cells. Additionally, it also prevents cell spreading in response to hormonal stimulation. High levels of calcium prevent recovery of normal microfilament organization and cell spreading following removal of cytochalasin B, but have no effect on normal microfilament organization alone. Additionally both the hydrocortisone induced spreading of C6 cells and increases in peripheral microfilaments are shown to be dependent on RNA ans protein synthesis. The levels of protein co-electrophoresing with actin are not effected by hydrocortisone.

Actins

Reversible inhibition of the hydrocortisone induction of glycerol phosphate dehydrogenase by cytochalasin B in rat glial C6 cells.

The hydrocortisone (HC) induction of glycerol phosphate dehydrogenase (GPDH; EC 1.1.1.8) in rat glial C6 cells was inhibited reversibly and in a dose-dependent manner by cytochalasin B (CB). CB had no effect on basal level GPDH, total cellular RNA, DNA or protein content nor did it act as a general inhibitor of the rate of protein synthesis. CB did not appear to be acting via dissociation of microtubules since colcemid had no effect on the induction process. The addition of an alternate energy source (sodium pyruvate) did not relieve the CB inhibition of GPDH induction suggesting that CB is not exerting its effect by blocking glucose utilization. The inhibition by CB is not dependent on the temporal sequence of the induction process since it specifically inhibited GPDH induction at any time it was added. CB did not alter the rate of degradation of GPDH in these cells and direct measurements of the specific rate of synthesis of GPDH demonstrated that CB decreased the induced rate of GPDH synthesis by about 60%. The site of inhibition was more precisely defined by experiments which demonstrated a 60% decrease in specific nuclear binding of 3H-HC even though total cellular uptake of 3H-HC was unaffected. This effect on nuclear binding of HC is sufficient to account for the decreased accumulation of GPDH activity in CB-treated cells.

Animals

Reversible inhibition of the norepinephrine induction of lactate dehydrogenase by cytochalasin B in rat glial C6 cells.

The cyclic AMP mediated induction of lactate dehydrogenase (LDH: E.C. 1.1.1.27) activity by norepinephrine in the rat glial cell line C6 is inhibited by cytochalasin B. Doses of 5, 15, and 25 microgram/ml of cytochalasin B inhibited the induction equally. Twenty-five microgram/ml of cytochalasin B inhibited the induction reversibly, and had no effect on basal enzyme level. No effect of cytochalasin B on general protein synthesis was found, nor did it increase the rate of decline of enzyme activity in deinduced cells. It therefore appears to block LDH induction by selectivity inhibiting its synthesis. Cytochalasin B had no effect on the transient (intracellular and extracelllular) rise in cyclic AMP generated in response to norepinephrine treatment. Cytochalasin B was effective when added during the transcription dependent phase (first 3 hours) but not during the translation dependent phase (after 3 hours) of LDH induction. The suggestion is discussed that cytochalasin B inhibits one of the early events of the inductive process.

Animals

Desmosterol in human and experimental brain tumors in tissue culture.

Desmosterol, a possible chemical indicator of brain tumors, was detected in cells of neurogenic, nitrosourea-induced rat tumors (neurinomas and gliomas, C6 cell line) and in human astrocytomas grown in lipid-poor media. A further increase in the amount of cell desmosterol was obtained when triparanol was added to media containing delipidized serum. Cholesterol was replaced almost completely by desmosterol in tumor cells grown in media containing nontoxic levels of 20,25-diazacholesterol. Desmosterol did not accumulate when these inhibitors of desmosterol-reductase were added to culture media containing cholesterol and other lipids (whole fetal calf serum). The results demonstrate that tumors of the nervous system grown in tissue culture are capable of sterol synthesis, and indicate that a central mechanism of cholesterol synthesis is operative in these cells, which may be related to the availability of exogenous cholesterol. It is concluded that these findings are relevant to clinical studies on the use of cholesterol inhibitors as tools for the detection of brain tumor activity.

Animals