Investigating the effect of verapamil on preservation of beta-cell function in adults with newly diagnosed type 1 diabetes mellitus (Ver-A-T1D): protocol for a randomised, double-blind, placebo-controlled, parallel-group, multicentre trial.

Introduction: Type 1 diabetes mellitus (T1DM) is a disorder that arises following the selective autoimmune destruction of the insulin-producing beta cells. Beta-cell protective or beta-cell regenerative approaches have gained wider attention, and pharmacological approaches to protect the patient's own insulin-producing beta-cell mass have been proposed. Verapamil is an L-type calcium channel blocker that has been reported to effectively lowers beta-cell thioredoxin-interacting protein expression in rodent beta cells and islets, as well as in human islets, and thus promotes functional beta-cell mass.

Ustekinumab for type 1 diabetes in adolescents: a multicenter, double-blind, randomized phase 2 trial.

Immunotherapy targeting the autoimmune process in type 1 diabetes (T1D) can delay the loss of β-cells but needs to have minimal adverse effects to be an adjunct to insulin in the management of T1D. Ustekinumab binds to the shared p40 subunit of interleukin (IL)-12 and IL-23, targeting development of T helper 1 cells and T helper 17 cells (T1 and T17 cells) implicated in the pathogenesis of T1D. We conducted a double-blind, randomized controlled trial of ustekinumab in 72 adolescents aged 12-18 years with recent-onset T1D.

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial.

Phase II multicentre, double-blind, randomised trial of ustekinumab in adolescents with new-onset type 1 diabetes (USTEK1D): trial protocol.

Introduction: Most individuals newly diagnosed with type 1 diabetes (T1D) have 10%-20% of beta-cell function remaining at the time of diagnosis. Preservation of residual beta-cell function at diagnosis may improve glycaemic control and reduce longer-term complications.Immunotherapy has the potential to preserve endogenous beta-cell function and thereby improve metabolic control even in poorly compliant individuals.

The use of randomisation-based efficacy estimators in non-inferiority trials.

Background: In a non-inferiority (NI) trial, analysis based on the intention-to-treat (ITT) principle is anti-conservative, so current guidelines recommend analysing on a per-protocol (PP) population in addition. However, PP analysis relies on the often implausible assumption of no confounders. Randomisation-based efficacy estimators (RBEEs) allow for treatment non-adherence while maintaining a comparison of randomised groups.

Electronic monitoring of medication adherence in a 1-year clinical study of 2 dosing regimens of mesalazine for adults in remission with ulcerative colitis.

Background: Adherence to medication is an issue of great importance for patients with ulcerative colitis. Once daily mesalazine seems to be no worse than divided doses in preventing relapse in remitting patients. Although this has been attributed to improved adherence, detailed measures of adherence have been lacking from previous studies.

One-year investigator-blind randomized multicenter trial comparing Asacol 2.4 g once daily with 800 mg three times daily for maintenance of remission in ulcerative colitis.

Background: Mesalazine (Asacol) is still widely prescribed in divided doses for ulcerative colitis (UC), despite evidence that adherence is improved by once-daily (OD) prescribing. We aimed to investigate whether OD Asacol was as effective as three times (TDS) daily dosing, and to evaluate the role of treatment adherence.

Methods: An investigator-blind randomized trial was undertaken comparing OD Asacol (three 800 mg tablets) versus one 800 mg TDS in maintenance of remission of UC over 1 year.

pH-conductivity hybrid gradient cation-exchange chromatography for process-scale monoclonal antibody purification.

The commercial production of recombinant human monoclonal antibody therapeutics demands robust processes. In this article we describe the development of a pH-conductivity hybrid gradient for a cation-exchange chromatography step to obtain high binding capacity and consistent purification resolution in scale process. Operational parameters and their ranges were characterized with DOE statistical method.

A new protocol for the in situ generation of aromatic, heteroaromatic, and unsaturated diazo compounds and its application in catalytic and asymmetric epoxidation of carbonyl compounds. Extensive studies to map out scope and limitations, and rationalization of diastereo- and enantioselectivities.

A variety of metalated tosylhydrazone salts derived from benzaldehyde have been prepared and were reacted with benzaldehyde in the presence of tetrahydrothiophene (THT) (20 mol %) and Rh(2)(OAc)(4) (1 mol %) to give stilbene oxide. Of the lithium, sodium, and potassium salts tested, the sodium salt was found to give the highest yield and selectivity. This study was extended to a wide variety of aromatic, heteroaromatic, aliphatic, alpha,beta-unsaturated, and acetylenic aldehydes and to ketones.

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy--a prospective, randomised, double-blind trial.

Background: Peristomal infection can sometimes complicate percutaneous endoscopic gastrostomy (PEG) placement. Antibiotic prophylaxis has, in some studies, been shown to reduce the incidence. However, the use of prophylaxis varies widely, possibly because the design and findings of the studies have differed, making their relevance to clinical practice difficult to interpret.

Crohn's disease incidence in Cardiff from 1930: an update for 1991-1995.

Objective: To report the incidence of Crohn's disease in the city of Cardiff between 1991 and 1995, in relation to the data of the preceding 65 years.

Methods: The incidence of Crohn's disease was studied by collecting information from clinical records, the department of pathology database and a questionnaire sent to local family practitioners.

Results: Eighty-four new patients with Crohn's disease, and resident in Cardiff, were diagnosed between 1991 and 1995.

A comparison of two rapid whole-blood tests and laboratory serology, in the diagnosis of Helicobacter pylori infection.

Objective: To compare two rapid whole-blood serology tests for Helicobacter pylori and a laboratory serology assay against a gold standard.

Design: Prospective comparison of tests in 81 patients.

Setting: A hospital rapid access endoscopy clinic.

Chemotherapy rapidly alternating with accelerated radiotherapy for advanced carcinoma of the uterine cervix.

The objective of this study was to determine the feasibility of treating patients with advanced cervical carcinoma using a regimen combining chemotherapy with intermittent hyperfractionated teletherapy. Eight patients with advanced cervical carcinoma were treated with bleomycin, ifosfamide and cisplatin, followed by a 5-day course of hyperfractionated external radiation. Three such courses were given at 21-day intervals.

The etiology and management of diarrhea in the gynecologic oncology patient.

Purpose: We determined the etiology and evaluated the usefulness of diagnostic tests in 42 gynecologic oncology patients with diarrhea.

Methods: All inpatients who developed diarrhea during treatment for gynecologic cancer were prospectively evaluated during the 12-month study period ending June 1992. Diarrhea was defined as five or more loose stools per 24 hr lasting for 48 hr or more.

Do we need second generation lithotripters in Hawaii?

The Kidney Stone Center of the Pacific (KSCoP) currently provides statewide services for kidney lithotripsy. The non-invasive technique uses shock waves to disintegrate kidney stones. Extracorporeal shock wave lithotripsy (ESWL) can be used successfully in 85% to 90% of kidney stone patients when surgery is indicated.

Incisional recurrence of squamous cell cervical carcinoma following operative staging.

A patient with FIGO Stage IIB cervical carcinoma underwent an extraperitoneal lymphadenectomy with exploratory laparotomy and washings for surgical staging. Intraperitoneal tumor was found. Seven months later, the tumor recurred as a subcutaneous nodule in the surgical incision.

A viable alternative to Medicare risk contracts and participation.

Throughout the 1980s, Medicare has 'turned against its service suppliers' and began to literally rewrite the rules of the health insurance game. This paper is set in that changing environment and describes one supplier's response.

Joint venture acquisition of expensive medical technology by Oahu hospitals. Planning, operations and impact of lithotripsy and magnetic resonance imaging.

Expensive diagnostic and treatment services and equipment are naturally suited to large, populous medical market areas, with sufficient forecasted service demand to justify the large investment in capital, construction and staffing. Only major tertiary or secondary medical centers with shared resources can justify the first-generation investment in the multimillion-dollar purchases of magnetic resonance imaging (MRI), megavoltage linear accelerators, or lithotripters. The regional referral system in most nations accommodates the outlying population in the less developed rural sectors.

Coronary artery-left ventricular communications: a report of two cases and review of the literature.

Two patients with chest pain had angiographically-demonstrated communications between the three coronary arteries and the left ventricular chamber. Communications between coronary arteries and the left ventricle are unusual and communications between all three coronary arteries and the left ventricle are rare. These anomalies are, however, commonly associated with symptoms of chest pain.