Continuous versus interrupted sutures for repair of episiotomy or second degree tears.

Background: Millions of women worldwide undergo perineal suturing after childbirth and the type of repair may have an impact on pain and healing. For more than 70 years, researchers have been suggesting that continuous non-locking suture techniques for repair of the vagina, perineal muscles and skin are associated with less perineal pain than traditional interrupted methods.

Objectives: To assess the effects of continuous versus interrupted absorbable sutures for repair of episiotomy and second degree perineal tears following childbirth.

Development of a model of patient satisfaction with physiotherapy.

The purpose of the study was to build a model to describe patient satisfaction with outpatient physiotherapy, basing this on need theory and theories from marketing research. The model was developed following interviews and focus groups with patients who had recently completed a course of outpatient physiotherapy for musculoskeletal conditions. It describes the patients' overall evaluation of their physiotherapy care in terms of satisfaction with 1) the Therapeutic Encounter and 2) Clinical Outcome.

Toward a theory of patient satisfaction with physiotherapy: exploring the concept of satisfaction.

Patient satisfaction is increasingly seen as an important area of research because it has been found that satisfied patients are more likely to benefit from their health care. However, there has been comparatively little work in this field within physiotherapy. Eliciting patients' expectations and needs of their care and addressing these during treatment could not only influence their subsequent health-related behaviour but could also contribute to a more favourable evaluation of the whole therapeutic experience.

Substrate-dependent inhibition kinetics of an active site-directed inhibitor of ADAMTS-4 (Aggrecanase 1).

ADAMTS-4 (aggrecanase-1) is implicated in the breakdown of articular cartilage and is an attractive target for therapeutic intervention in arthritis. Cleavage of the native substrate, aggrecan, occurs through exosite interactions and peptide sequence recognition. Although expected to be competitive with aggrecan, the hydroxamic acid, SC81956, demonstrated noncompetitive inhibition kinetics with a Ki of 23 nM.

FLT3 tyrosine kinase domain mutations are biologically distinct from and have a significantly more favorable prognosis than FLT3 internal tandem duplications in patients with acute myeloid leukemia.

The prognostic impact of tyrosine kinase domain (TKD) mutations of the fms-like tyrosine kinase-3 (FLT3) gene in acute myeloid leukemia (AML) is currently uncertain. To resolve this issue we screened 1107 young adult nonacute promyelocytic leukemia AML patients with known FLT3 internal tandem duplication (ITD) status for FLT3/TKDs; they were detected in 127 (11%) cases. Mutations were associated with a high white cell count (P =.

Satisfaction with outpatient physiotherapy: a survey comparing the views of patients with acute and chronic musculoskeletal conditions.

Patient satisfaction is a complex construct and is regarded as an important component in the assessment of care quality. Investigations into patient satisfaction with care have steadily increased across a range of specialties over the last three decades, but there has been a paucity of studies into satisfaction with physiotherapy. The limitations of previous instruments used to examine satisfaction with outpatient (OP) physiotherapy suggested the need for a new tool.

Satisfaction with outpatient physiotherapy: focus groups to explore the views of patients with acute and chronic musculoskeletal conditions.

Patient satisfaction is generally regarded as an important component in quality health care. However, there has been little satisfaction research in physiotherapy compared with that in other clinical fields with few qualitative studies that have explored patients' perceptions and attitudes toward physiotherapy. We report on the use of focus groups, as part of a multimethod approach of qualitative data collection into patients' satisfaction with their outpatient physiotherapy within the NHS system of care in the United Kingdom.

Development of a fluorescence-based enzyme assay of human 5-lipoxygenase.

Leukotrienes are important mediators in a number of inflammatory diseases and therefore are a target of several therapeutic approaches. The first committed step in the synthesis of leukotrienes is the conversion of arachidonic acid to leukotriene A(4) (LTA(4)) in two successive reactions catalyzed by 5-lipoxygenase (5-LOX). Assays to measure 5-LOX activity typically have been low throughput and time consuming.

Hydrophobic cooperativity as a mechanism for amyloid nucleation.

The kinetics of amyloid fibril formation are in most cases explained by classical nucleation theory, yet the mechanisms behind nucleation are not well understood. We show using molecular dynamics simulations that the hydrophobic cooperativity in the self-association of the model amyloidogenic peptide STVIYE is sufficient to allow for nucleation-dependent polymerization with a pentamer critical nucleus. The role of electrostatics was also investigated.

A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment.

Background: The survival of older patients with acute myeloid leukemia has not improved. Few clinical trials have been available for older patients who are not considered fit for an intensive chemotherapy approach.

Methods: Between December 1998 and November 2003, as part of National Cancer Research Institute Acute Myeloid Leukemia 14 Trial, 217 patients, who were deemed unfit for intensive chemotherapy were randomized to receive low-dose cytarabine (Ara-C) (20 mg twice daily for 10 days) or hydroxyurea with or without all-trans retinoic acid (ATRA).

Identification of an ADAMTS-4 cleavage motif using phage display leads to the development of fluorogenic peptide substrates and reveals matrilin-3 as a novel substrate.

ADAMTS-4 and ADAMTS-5 are aggrecanases responsible for the breakdown of cartilage aggrecan in osteoarthritis. Multiple ADAMTS-4 cleavage sites have been described in several matrix proteins including aggrecan, versican, and brevican, but no concise predictive cleavage motif has been identified for this protease. By screening a 13-mer peptide library with a diversity of 10(8), we have identified the ADAMTS-4 cleavage motif E-(AFVLMY)-X(0,1)-(RK)-X(2,3)-(ST)-(VYIFWMLA), with Glu representing P1.

Assessing new interventions in women's health.

One of the most frequent clichés in evidence-based medicine (EBM) is that 'without evidence there can be no evidence-based practice'. How best to assemble evidence on the effectiveness (or ineffectiveness) of a treatment is central to the entire concept of EBM. Particularly in women's health, where even small or moderate improvements in the individual well-being of one woman can lead to an enormous impact on the overall health of the nation, it is important to be able to detect or refute reliably small to moderate treatment effects.

Factors predisposing women to chronic pelvic pain: systematic review.

Objective: To evaluate factors predisposing women to chronic and recurrent pelvic pain. DESIGN, DATA SOURCES, AND METHODS: Systematic review of relevant studies without language restrictions identified through Medline, Embase, PsycINFO, Cochrane Library. SCISEARCH, conference papers, and bibliographies of retrieved primary and review articles.

Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials.

Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience in the Medical Research Council (MRC) AML 10 and AML 12 trials, which enrolled 46 children with ML-DS from 1988 to 2002. Eight per cent of UK children with AML had DS, but DS children comprised only 5% of children registered in MRC trials.

A randomised-controlled trial in England of a postnatal midwifery intervention on breast-feeding duration.

Objective: To determine whether postnatal 'hands off' care by midwives on positioning and attachment of the newborn baby improves breast-feeding duration.

Design: Mothers were randomised at the first postnatal feed to receive either care by a midwife trained in the experimental protocol or by a control midwife undertaking routine care.

Setting: Eight wards in four English Midlands hospitals.

Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials.

Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested the role of bone marrow transplantation following four blocks of intensive chemotherapy and found that while both allogeneic bone marrow transplant (allo-BMT) and autologous bone marrow transplant (A-BMT) significantly reduced the relapse risk (RR), this did not translate into a significant improvement in overall survival (OS). A risk group stratification based on cytogenetics and response to the first course of chemotherapy derived from MRC AML 10 was used to deliver risk-directed therapy in MRC AML 12.

ADAMTS-4 (aggrecanase-1): N-terminal activation mechanisms.

ADAMTS-4 (aggrecanase 1) is synthesized as a latent precursor protein that may require activation through removal of its prodomain before it can exert catalytic activity. We examined various proteinases as well as auto-activation under a wide range of conditions for removal of the prodomain and induction of enzymatic activity. The proprotein convertases, furin, PACE4, and PC5/6 efficiently removed the prodomain through cleavage at Arg(212)/Phe(213), generating an active enzyme.

Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia.

The prognostic significance of FLT3 mutations in acute promyelocytic leukemia (APL) is not firmly established and is of particular interest given the opportunities for targeted therapies using FLT3 inhibitors. We studied 203 patients with PML-RARA-positive APL; 43% of the patients had an FLT3 mutation (65 internal tandem duplications [ITDs], 19 D835/I836, 4 ITD+D835/I836). Both mutations were associated with higher white blood cell (WBC) count at presentation; 75% of the patients with WBC counts of 10 x 10(9)/L or greater had mutant FLT3.

No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials.

Fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) are powerful adverse prognostic indicators for relapse in acute myeloid leukemia (AML) but the most efficacious therapy for FLT3/ITD(+) patients is currently unknown. We evaluated outcome according to FLT3/ITD status in 1135 adult patients treated according to United Kingdom Medical Research Council (UK MRC) AML protocols: 141 received an autograft, and 170 received a matched sibling allograft in first complete remission (CR). An FLT3/ITD was detected in 25% of patients and was an independent predictor for relapse (P < .