A single harmonised pharmacy process to improve clinical trial set-up times.

The UK has fallen from fourth to 10th place in the global ranking for clinical trial activities in the past 6 years. Due to the limited capacity of the clinical trial pharmacy workforce and delays in providing pharmacy approvals, pharmacy has been identified as one of the constraining services that delays the set-up and delivery of clinical trials. To tackle this problem, we developed a single pharmacy review process for multicentre trials across Greater Manchester (GM) and tested its feasibility and implementation in our region.

Early diagnosis and successful long-term management of a rare, severe lysosomal acid lipase deficiency/Wolman disease patient: Infancy to age five.

Background: This report describes a unique case of long-term survival of a young girl who was diagnosed with severe, rapidly progressive lysosomal acid lipase deficiency (LAL-D; historically "Wolman disease") at three months of age and began receiving therapeutic interventions at four months of age. This disease involves rapidly progressive multisystemic impairments and limited survival (6-12 months) without treatment.

Methods: Case report taking into account clinical aspects and patient management including a semi-structured interview with the main family caregiver.

Clinical performance of primary HPV screening cut-off for colposcopy referrals in HPV-vaccinated cohort: Observational study.

Objective: To understand the effect of changing from cytology-based to primary HPV screening on the positive predictive value (PPV) of colposcopy referrals for cervical intraepithelial neoplasia (CIN) in a cohort offered HPV vaccination.

Design: Retrospective pre/post observational cohort study.

Setting: Scotland.

Insights into the Antibacterial Mechanism of Action of Chelating Agents by Selective Deprivation of Iron, Manganese, and Zinc.

Bacterial growth and proliferation can be restricted by limiting the availability of metal ions in their environment. Humans sequester iron, manganese, and zinc to help prevent infection by pathogens, a system termed nutritional immunity. Commercially used chelants have high binding affinities with a variety of metal ions, which may lead to antibacterial properties that mimic these innate immune processes.

On the Antibacterial Activity of Azacarboxylate Ligands: Lowered Metal Ion Affinities for Bis-amide Derivatives of EDTA do not mean Reduced Activity.

EDTA is widely used as an inhibitor of bacterial growth, affecting the uptake and control of metal ions by microorganisms. We describe the synthesis and characterisation of two symmetrical bis-amide derivatives of EDTA, featuring glycyl or pyridyl substituents: AmGly and AmPy . Metal ion affinities (logK) have been evaluated for a range of metals (Mg , Ca , Fe , Mn , Zn ), revealing less avid binding compared to EDTA.

Effects of bovine colostrum supplementation on upper respiratory illness in active males.

Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise-induced immune dysfunction and increased risk of upper respiratory illness (URI) in athletic populations, however, the mechanisms remain unclear. During winter months, under double-blind procedures, 53 males (mean training load±SD, 50.5±28.

CT should replace three-view radiographs as the initial screening test in patients at high, moderate, and low risk for blunt cervical spine injury: a prospective comparison.

Background: An estimated 10,000 Americans suffer cervical spine injuries each year. More than 800,000 cervical spine radiographs (CSR) are ordered annually. The human and healthcare costs associated with these injuries are enormous especially when diagnosis is delayed.

Posterior displacement of a proximal epiphyseal clavicle fracture.

Posterior clavicle dislocations are uncommon injuries but are associated with serious complications based on their proximity to mediastinal structures. In children, the physis is the weakest point structurally, making a displaced Salter I fracture more common than a true sternoclavicular joint dislocation. This injury may be missed on exam and routine radiographs unless a high suspicion is maintained.

Symptom resolution in patients with Mycoplasma pneumoniae pneumonia.

Background: Mycoplasma pneumoniae generally causes pneumonia of mild to moderate severity in adults. However, little is known about the time course of the resolution of symptoms in this illness.

Objectives: To determine the time course of the resolution of symptoms in M pneumoniae pneumonia.

Resolution of symptoms in patients with community-acquired pneumonia treated on an ambulatory basis.

Objective: To describe the resolution of five symptoms commonly associated with community-acquired pneumonia (CAP).

Methods: Three hundred and ninety-nine patients with CAP (Fine Classes I to III) recorded the severity (from 0 to 5) of fatigue, cough, dyspnoea, sputum, and pleuritic chest pain daily from enrollment to day 14 and also on days 30 and 42. A total symptom score was obtained by multiplying an individual score by four and summing the score of the five symptom (transformed score).

A multicentre randomized controlled trial of expectant management versus IVF in women with Fallopian tube patency.

Background: Although observational studies suggest that IVF is more effective than no treatment for women with Fallopian tube patency, this has not been tested rigorously in a randomized controlled trial (RCT).

Methods: Eligible consenting couples planning their first treatment cycle in five Canadian fertility clinics received either IVF, within 90 days of randomization, or a period of 90 days with no treatment. Random allocation was stratified by female age and sperm quality, and administered using numbered, opaque, sealed envelopes.

Characterising doctor-parent communication in counselling for impending preterm delivery.

Objective: To examine the counselling of women admitted to hospital in preterm labour. Such women and their partners are often asked to participate in difficult decisions including mode of delivery, fetal monitoring, and resuscitation.

Study Design: Questionnaire based descriptive study.

Chemokine RANTES promoter polymorphism affects risk of both HIV infection and disease progression in the Multicenter AIDS Cohort Study.

Objective: To examine whether polymorphism in the RANTES gene is associated with HIV disease outcome.

Design: RANTES, a ligand of the major HIV co-receptor, CCR5, is known to block HIV-CCR5 interactions. Recently, two single nucleotide polymorphisms in the RANTES gene promoter region, designated -403G/A and -28C/G, have been described.

Albumin-corrected calcium and ionized calcium in stable haemodialysis patients.

Background: It is ionized calcium that is physiologically active and under homeostatic control; however, total calcium is more conveniently measured. Formulae for correction of calcium to account for albumin binding have not been validated in a dialysis setting.

Methods: We measured ionized calcium simultaneously with total calcium (t[Ca]), albumin, total protein and pH before dialysis in 50 stable outpatients and convalescent inpatients.

Randomized trial of a "stage-of-change" oriented smoking cessation intervention in infertile and pregnant women.

Objective: To assess a "stage-of-change" oriented smoking cessation intervention for infertile and pregnant women, compared with standard of care.

Design: Randomized controlled trial.

Setting: Three university teaching hospitals in Hamilton, Ontario, Canada.

Lysine: N6-hydroxylase: stability and interaction with ligands.

Recombinant lysine:N6-hydroxylase, rIucD, which is isolated as an apoenzyme, requires FAD and NADPH for its catalytic function. rIucD preparations have been found to undergo time-dependent loss in monooxygenase function due to aggregation from the initial tetrameric state to a polytetrameric form(s), a process which is reversible by treatment with thiols. Ligand-induced conformational changes in rIucD were assessed by monitoring its CD spectra, DSC profile, and susceptibility to both endo- as well as exopeptidases.

Acyclophostin: a ribose-modified analog of adenophostin A with high affinity for inositol 1,4,5-trisphosphate receptors and pH-dependent efficacy.

Adenophostin A is the most potent known agonist of D-myo-inositol 1, 4,5-trisphosphate [Ins(1,4,5)P3] receptors. Equilibrium competition binding studies with 3H-Ins(1,4,5)P3 showed that the interaction of a totally synthetic adenophostin A with both hepatic and cerebellar Ins(1,4,5)P3 receptors was indistinguishable from that of the natural product. At pH 8.

Luminal Ca2+ regulates passive Ca2+ efflux from the intracellular stores of hepatocytes.

Ca2+ uptake into the intracellular stores of permeabilized hepatocytes was entirely dependent on ATP and substantially inhibited by either ionomycin or thapsigargin, although both were required for complete inhibition. Unidirectional efflux of 45Ca2+ after removal of ATP from cells loaded to steady state (1.60+/-0.

Disaccharide polyphosphates based upon adenophostin A activate hepatic D-myo-inositol 1,4,5-trisphosphate receptors.

The glyconucleotides adenophostin A and B are the most potent known agonists at type 1 inositol trisphosphate [Ins(1,4,5)P3] receptors, although their stuctures differ markedly from that of Ins(1,4,5)P3. Equilibrium competition binding with [3H]Ins(1,4,5)P3 and unidirectional 45Ca2+ flux measurements were used to examine the effects of adenophostin A in hepatocytes, which express predominantly type 2 Ins(1,4,5)P3 receptors. Both Ins(1,4,5)P3 (Kd = 8.

Incremental Ca2+ mobilization by inositol trisphosphate receptors is unlikely to be mediated by their desensitization or regulation by luminal or cytosolic Ca2+.

The kinetics of Ins(1,4,5)P3 (InsP3)-stimulated Ca2+ release from intracellular stores are unusual in that submaximal concentrations of InsP3 rapidly release only a fraction of the InsP3-sensitive Ca2+ stores. By measuring unidirectional 45Ca2+ efflux from permeabilized rat hepatocytes, we demonstrate that such quantal responses to InsP3 occur at all temperatures between 2 and 37 degrees C, but at much lower rates at the lower temperatures. Preincubation with submaximal concentrations of InsP3, which themselves evoked quantal Ca2+ release, had no effect on the sensitivity of the stores to further additions of InsP3.

Cost analysis of dialysis treatments for end-stage renal disease (ESRD).

The cost of alternative dialysis modalities for the treatment of end-stage renal disease (ESRD) was evaluated, using a societal viewpoint, in a regional nephrology program in south-western Ontario. The dialysis treatments compared were hospital hemodialysis, home hemodialysis, self-care hemodialysis, and continuous ambulatory peritoneal dialysis (CAPD). The participants were all patients treated by the same dialysis modality for the fiscal year April 1990 to March 1991.

Effect of recombinant human erythropoietin on hospitalization of hemodialysis patients.

The effect of recombinant human erythropoietin (EPO) on hospitalization of patients with end-stage renal disease (ESRD) was evaluated in a controlled clinical trial. A cohort of 67 new hemodialysis patients prescribed EPO shortly after the clinical availability of EPO were the treatment group. The control group was a cohort of 67 new hemodialysis patients matched for clinical center, age, cardiovascular disease and transfusion history.