Protocol for an independent patient data meta-analysis of prophylactic mesh placement for incisional hernia prevention after abdominal aortic aneurysm surgery: a collaborative European Hernia Society project (I-PREVENT-AAA).

Introduction: Incisional hernia (IH) is a prevalent and potentially dangerous complication of abdominal surgery, especially in high-risk groups. Mesh reinforcement of the abdominal wall has been studied as a potential intervention to prevent IHs. Randomised controlled trials (RCTs) have demonstrated that prophylactic mesh reinforcement after abdominal surgery, in general, is effective and safe.

A risk-adjusted and anatomically stratified cohort comparison study of open surgery, endovascular techniques and medical management for juxtarenal aortic aneurysms-the UK COMPlex AneurySm Study (UK-COMPASS): a study protocol.

Introduction: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?'

Methods And Analysis: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases.

An Implanted Blood Vessel Support Device for Arteriovenous Fistulas: A Randomized Controlled Trial.

Rationale & Objective: Reducing turbulent blood flow through dialysis arteriovenous fistulas (AVFs) and radial stretching of their venous wall may attenuate hyperplasia and stenosis and improve AVF outcomes in hemodialysis patients. The goal of this study was to evaluate the safety and efficacy of the VasQ implant, which intervenes on these mechanisms by physically supporting the surgical arteriovenous anastomosis.

Study Design: Prospective, randomized, controlled, multicenter study.

Acute aortic dissection: a missed diagnosis.

A 60-year-old man with a history of indigestion and untreated hypertension presented with sudden-onset central chest pain which radiated to his back. Acute coronary syndrome was initially suspected but excluded in the emergency department before the patient was discharged. The pain subsequently abated to mild intermittent episodes and was misdiagnosed as indigestion.

The association between referral source and outcome in patients with colorectal cancer.

Aim: The colorectal two-week wait fast track (FT) referral system was nationally implemented in the UK in 2000 to ensure patients with colorectal cancer (CRC) received prompt access to specialized services. The aim of this study was to determine the association between the mechanism of referral to colorectal services and the 5-year outcomes for patients with CRC.

Methods: Consecutive patients with newly diagnosed CRC presenting between October 2002 and September 2004 were identified retrospectively.

Slipping through the bowel cancer screening programme.

Aim: Colorectal cancer is common and a leading cause of cancer death. Faecal occult blood screening has been shown to reduce mortality. The aim of this study was to identify patients in Gloucestershire with a new diagnosis of colorectal cancer who had previously been screened via the Bowel Cancer Screening Programme (BCSP).

Venous ulcer review.

Clinical Question: What is the best treatment for venous ulcers?

Results: Compression aids ulcer healing. Pentoxifylline can aid ulcer healing. Artificial skin grafts are more effective than other skin grafts in helping ulcer healing.

Randomized clinical trial of mesh versus sutured wound closure after open abdominal aortic aneurysm surgery.

Background: Incisional herniation is a common complication of abdominal aortic aneurysm (AAA) repair. This study investigated whether prophylactic mesh placement could reduce the rate of postoperative incisional hernia after open repair of AAA.

Methods: This randomized clinical trial was undertaken in three hospitals.

Radiocephalic and brachiocephalic arteriovenous fistula outcomes in the elderly.

Background: A recent meta-analysis has suggested that patients aged >65 have worse outcomes with radiocephalic arteriovenous fistulas (RCAVFs) compared with brachiocephalic arteriovenous fistulas (BCAVFs). We hypothesized that outcomes in patients aged > or = 80--a rapidly expanding cohort within this elderly group--might be skewing the results, and that age >65 may not be a contraindication to RCAVF formation. This study examined the effect of age group (<65, 65 to 79, >or =80) on functional outcomes (use; primary and secondary functional patency) in RCVAFs and BCAVFs.

A comparison between transposed brachiobasilic arteriovenous fistulas and prosthetic brachioaxillary access grafts for vascular access for hemodialysis.

Objective: Patients requiring access for hemodialysis in whom radiocephalic or brachiocephalic arteriovenous fistulas cannot be formed or have failed present a significant clinical challenge. We compare outcomes in patients undergoing transposed brachiobasilic arteriovenous fistulas (BBAVF) with expanded polytetrafluoroethylene brachioaxillary access grafts in a single European center.

Methods: We identified all patients undergoing a first upper limb tertiary-access procedure-that is, either BBAVF or brachioaxillary access graft for hemodialysis-between January 1, 2000, and December 31, 2005.

The association between referral source and stage of disease in patients with colorectal cancer.

Objective: The colorectal fast track (FT) referral system was set up to ensure patients with suspected cases of colorectal cancer (CRC) received prompt access to specialized services. The aim of this study was to ascertain the association between referral source and the time it took to be seen by a colorectal surgeon to establish whether referral source had any association with the stage of disease at presentation in patients with CRC.

Method: Consecutive patients with newly diagnosed CRC presenting between October 2002 and September 2004 were identified retrospectively.

Wound oozing after total hip arthroplasty.

Introduction: Total hip arthroplasty is a commonly performed operation and yet little information exists about the duration of wound oozing, the factors associated with this and the implications. The aim of this work was to identify factors influencing wound oozing by establishing their effect on the time taken for wounds to cease oozing after total hip arthroplasty.

Patients And Methods: Sixty-two consecutive patients undergoing total hip arthroplasty were included.

Disordered osteoclast formation and function in a CD38 (ADP-ribosyl cyclase)-deficient mouse establishes an essential role for CD38 in bone resorption.

We have evaluated the role of the ADP-ribosyl cyclase, CD38, in bone remodeling, a process by which the skeleton is being renewed constantly through the coordinated activity of osteoclasts and osteoblasts. CD38 catalyzes the cyclization of its substrate, NAD+, to the Ca2+-releasing second messenger, cyclic ADP-ribose (cADPr). We have shown previously that CD38 is expressed both in osteoblasts and osteoclasts.

Forty years of calcitonin--where are we now? A tribute to the work of Iain Macintyre, FRS.

Calcitonin was discovered as a hypocalcemic principal that was initially thought to originate from the parathyroid gland. This view was corrected subsequently, and an origin from the thyroid C cells was documented. The purification and sequencing of various calcitonins soon followed.

Ca(2+) influx through the osteoclastic plasma membrane ryanodine receptor.

We predict that the type 2 ryanodine receptor isoform (RyR-2) located in the osteoclastic membrane functions as a Ca(2+) influx channel and as a divalent cation (Ca(2+)) sensor. Cytosolic Ca(2+) measurements revealed Ca(2+) influx in osteoclasts at depolarized membrane potentials. The cytosolic Ca(2+) change was, as expected, not seen in Ca(2+)-free medium and was blocked by the RyR modulator ryanodine.

A novel mechanism for coupling cellular intermediary metabolism to cytosolic Ca2+ signaling via CD38/ADP-ribosyl cyclase, a putative intracellular NAD+ sensor.

CD38 is an ectocyclase that converts NAD+ to the Ca2+-releasing second messenger cyclic ADP-ribose (cADPr). Here we report that in addition to CD38 ecto-catalysis, intracellularly expressed CD38 may catalyze NAD+-->cADPr conversion to cause cytosolic Ca2+ release. High levels of CD38 were found in the plasma membranes, endoplasmic reticulum, and nuclear membranes of osteoblastic MC3T3-E1 cells.

Molecular cloning, expression, and functional characterization of a novel member of the CD38 family of ADP-ribosyl cyclases.

We report the molecular cloning and functional characterization of a novel member of the CD38 family of cyclic ADP-ribose (cADPr)-generating cyclases. We cloned a cDNA insert that encoded a 298-amino-acid-long protein (M(w) approximately 39 kDa). The predicted protein displayed 69, 61, and 58% similarity, respectively, to mouse, rat, and human CD38.

Novel biochemical and functional insights into nuclear Ca(2+) transport through IP(3)Rs and RyRs in osteoblasts.

We report the first biochemical and functional characterization of inositol trisphosphate receptors (IP(3)Rs) and ryanodine receptors (RyRs) in the nuclear membrane of bone-forming (MC3T3-E1) osteoblasts. Intact nuclei fluoresced intensely with anti-RyR (Ab(34)) and anti-IP(3)R (Ab(40)) antisera in a typically peripheral nuclear membrane pattern. Isolated nuclear membranes were next subjected to SDS-PAGE and blotted with isoform-specific anti-receptor antisera, notably Ab(40), anti-RyR-1, anti-RyR-2 (Ab(129)), and anti-RyR-3 (Ab(180)).

A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis.

Nucleoplasmic calcium ions (Ca2+) influence nuclear functions as critical as gene transcription, apoptosis, DNA repair, topoisomerase activation and polymerase unfolding. Although both inositol trisphosphate receptors and ryanodine receptors, types of Ca2+ channel, are present in the nuclear membrane, their role in the homeostasis of nuclear Ca2+ remains unclear. Here we report the existence in the inner nuclear membrane of a functionally active CD38/ADP-ribosyl cyclase that has its catalytic site within the nucleoplasm.

CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption.

The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr). The latter gates Ca(2+) release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library.

Meloxicam pharmacokinetics in renal impairment.

Aims: The aim of the present study was to determine how the pharmacokinetics of meloxicam are affected by kidney dysfunction and consequently to define the appropriate dose for the use of meloxicam in patients with mild or moderate renal impairment.

Methods: Meloxicam was administered to subjects with mild (creatinine clearance 41-60 ml min-1) to moderate (20-40 ml min-1) renal impairment compared with normal renal function (> 60 ml min-1). Thirty-eight subjects received meloxicam 15 mg once daily over 9 days.

Evaluation of the safety, tolerability, and efficacy of meloxicam tablets in patients with osteoarthritis.

This 12-week, open-label, multicenter study assessed the safety, tolerability, and efficacy of the tablet formulation of meloxicam 15 mg, a new, nonsteroidal antiinflammatory drug (NSAID), in patients with confirmed osteoarthritis (OA) of the hip or knee. Meloxicam differs from established NSAIDs in its preferential activity against cyclooxygenase type 2 compared with cyclooxygenase type 1. One hundred thirty-nine patients were given meloxicam tablets 15 mg once daily.

An open study to assess the safety and tolerability of meloxicam 15 mg in subjects with rheumatic disease and mild renal impairment.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which has shown potent anti-inflammatory properties but good gastrointestinal (GI) renal tolerability. The safety and tolerability profile of orally administered meloxicam 15 mg given once daily over a 28 day treatment period in renally impaired patients with rheumatic disease is presented here. A total of 25 patients (aged 43-78 yr, mean age 70 yr) with rheumatic disease and mild renal impairment were enrolled in this multicentre, open-label study, with 22 patients completing the 28 day treatment period.