Rationale and design of the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) trial.

Exenatide once-weekly is an extended release formulation of exenatide, a glucagon-like peptide-1 receptor agonist, which can improve glycemic control, body weight, blood pressure, and lipid levels in patients with type 2 diabetes mellitus (T2DM). The EXenatide Study of Cardiovascular Event Lowering (EXSCEL) will compare the impact of adding exenatide once-weekly to usual care with usual care alone on major cardiovascular outcomes. EXSCEL is an academically led, phase III/IV, double-blind, pragmatic placebo-controlled, global trial conducted in 35 countries aiming to enrol 14,000 patients with T2DM and a broad range of cardiovascular risk over approximately 5 years.

Beyond indicators: advances in global HIV monitoring and evaluation during the PEPFAR era.

Monitoring and evaluation (M&E) is fundamental to global HIV program implementation and has been a cornerstone of the President's Emergency Plan for AIDS Relief (PEPFAR). Rapid results were crucial to demonstrating feasibility and scalability of HIV care and treatment services early in PEPFAR. When national HIV M&E systems were nascent, the rapid influx of funds and the emergency expansion of HIV services contributed to the development of uncoordinated "parallel" information systems to serve donor demands for information.

Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial.

Background: Most patients with type 2 diabetes begin pharmacotherapy with metformin, but eventually need additional treatment. We assessed the safety and efficacy of once weekly exenatide, a glucagon-like peptide 1 receptor agonist, versus maximum approved doses of the dipeptidyl peptidase-4 inhibitor, sitagliptin, or the thiazolidinedione, pioglitazone, in patients treated with metformin.

Methods: In this 26-week randomised, double-blind, double-dummy, superiority trial, patients with type 2 diabetes who had been treated with metformin, and at baseline had mean glycosylated haemoglobin (HbA(1c)) of 8.

DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks.

Objective: In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) study, the safety and efficacy of 30 weeks of treatment with the glucagon-like peptide-1 receptor agonist exenatide once weekly (exenatide QW; 2 mg) was compared with exenatide BID in 295 patients with type 2 diabetes. We now report the safety and efficacy of exenatide QW in 1) patients who continued treatment for an additional 22 weeks (52 weeks total) and 2) patients who switched from exenatide BID to exenatide QW after 30 weeks.

Research Design And Methods: In this randomized, multicenter, comparator-controlled, open-label trial, 258 patients entered the 22-week open-ended assessment phase (n = 128 QW-only; n = 130 BID-->QW).

Rosiglitazone reduces microalbuminuria and blood pressure independently of glycemia in type 2 diabetes patients with microalbuminuria.

Objective: To test the hypothesis that rosiglitazone combined with metformin provides a greater reduction in microalbuminuria and blood pressure than metformin and glyburide at comparable levels of glycemic control.

Methods: In a double-blind, parallel-group design 389 participants with type 2 diabetes were followed for 32 weeks.

Results: Urinary albumin: creatinine ratio was significantly reduced at 32 weeks compared with baseline in the rosiglitazone plus metformin group (-22.

Effect of early addition of rosiglitazone to sulphonylurea therapy in older type 2 diabetes patients (>60 years): the Rosiglitazone Early vs. SULphonylurea Titration (RESULT) study.

Aim: To compare the efficacy, safety and tolerability of adding rosiglitazone (RSG) vs. sulphonylurea (SU) dose escalation in older type 2 diabetes mellitus (T2DM) patients inadequately controlled on SU therapy.

Methods: A total of 227 T2DM patients from 48 centres in the USA and Canada, aged > or =60 years, were randomized to receive RSG (4 mg) or placebo once daily in combination with glipizide 10 mg twice daily for 2 years in a double-blind, parallel-group study.

Rosiglitazone, but not glyburide, reduces circulating proinsulin and the proinsulin:insulin ratio in type 2 diabetes.

An elevation in the ratio of proinsulin (PI) to immunoreactive insulin (IRI) is inversely related to beta-cell function in type 2 diabetes, and increased PI is an independent risk factor for coronary heart disease. An objective of the present studies was to assess the effects of the thiazolidinedione insulin sensitizer, rosiglitazone, on indirect markers of beta-cell function and cardiovascular risk in people with type 2 diabetes by measuring plasma PI and the PI:IRI ratio. Parameters of insulin processing, including plasma PI and PI:IRI ratios, were determined in type 2 diabetes patients enrolled in two randomized double-blind studies comparing the effects of rosiglitazone (4 or 8 mg/d) with placebo (study 1, 26-wk treatment) or the sulfonylurea glyburide (study 2, 52-wk treatment).

An unusual incident: breached 22Na sealed source.

A typical laboratory contamination with radioactive materials in an academic institution is the result of a spill or other handling errors with unsealed radioactive materials. An unusual incident occurred in late January 2002 at our institution when a 22Na sealed source was breached, and a small portion of the contents accidentally migrated to various locations in the very large laboratory. Damage control provided a challenge to radiation safety personnel.

Does the peak-end phenomenon observed in laboratory pain studies apply to real-world pain in rheumatoid arthritics?

Laboratory studies and investigations of patients undergoing painful procedures have compared recalled pain to an average of multiple momentary reports taken throughout the painful experience. This work has shown that recalled ratings of pain are more closely associated with a combination of peak pain and pain proximal to the recall ratings than an average of all momentary reports. However, these studies have examined recalled pain over relatively short periods, usually under 1 hour.

Rosiglitazone reduces urinary albumin excretion in type II diabetes.

This study examines the effect of rosiglitazone on urinary albumin excretion (UAE) in patients with type II diabetes. Urinary albumin: creatinine ratio (ACR) was measured in a 52-week, open-label, cardiac safety study comparing rosiglitazone and glyburide. Patients were randomised to treatment with rosiglitazone 4 mg b.

Use of reproductive health services among young men, 1995.

Purpose: To analyze the extent to which teenage males receive preventive reproductive health services and identify demographic and health factors associated with their receipt.

Methods: Bivariate and multivariate analyses of nationally representative data from the 1995 National Survey of Adolescent Males were conducted using logistic regression to determine which factors predicted whether teenagers had a physical examination and whether they discussed reproductive health topics with a medical professional, had a human immunodeficiency virus (HIV) test, or had a sexually transmitted disease (STD) test.

Results: Although 71% of males aged 15-19 years received a physical examination in the past year, only 39% of them received any of the three reproductive health services.

The paradox of the low-renin state in diabetic nephropathy.

Although diabetic nephropathy is often a low renin state, the renin system appears to be implicated in its pathogenesis. In this study, it was hypothesized that the low plasma renin activity (PRA) is misleading, masking and perhaps reflecting an activated intrarenal renin system. PRA and renal vascular responses (inulin and para-aminohippurate clearance) to graded doses of an angiotensin II (AngII) antagonist, irbesartan, were assessed in eight healthy volunteers and 12 patients with type 2 diabetes mellitus and nephropathy on a 10 mmol Na intake, to activate the renin system.

Laparoscopic biopsy for suspected abdominal lymphoma.

This study retrospectively reviewed the findings in laparoscopic biopsy specimens from 51 consecutive patients with suspected abdominal lymphoproliferative disorders. Histologic evaluation was supplemented (as necessary) by paraffin-section or frozen-section immunohistochemical analysis or by Southern blot hybridization. The laparoscopic procedure was diagnostic of a lymphoproliferative disorder in 24 patients (47%), of other neoplasms in 5 patients (10%), and of reactive tissue in 11 patients (22%); no tissue could be obtained for technical reasons (adhesions and inaccessible lesions) in 11 patients (22%).

Obesity, salt intake, and renal perfusion in healthy humans.

Renal perfusion rises as obesity develops during short-term overfeeding in animal studies. In humans, the assessment is complicated by the need to normalize renal perfusion for body size. We made use of the fact that radioactive xenon washout measures renal perfusion per unit of tissue mass to address this issue by comparing 45 moderately obese and 147 lean healthy potential kidney donors.

T cell activation and retargeting using staphylococcal enterotoxin B and bispecific antibody: an effective in vivo antitumor strategy.

The aim of this work was to test for cure and immunity in a micrometastatic tumor model using in vivo T cell activation with staphylococcal enterotoxin B (SEB) and retargeting with antitumor x anti-CD3 F(ab')2 bispecific antibodies (bsAb). All studies were performed in C3H/HeN mice using syngeneic tumor cell lines. For survival studies, mice were injected intravenously on day 0 with CL62 (a p97-transfected clone of the K1735 murine melanoma tumor).

Analysis of bacterial carbapenem antibiotic production genes reveals a novel β-lactam biosynthesis pathway.

Carbapenems are β-lactam antibiotics which have an increasing utility in chemotherapy, particularly for nosocomial, multidrug-resistant infections. Strain GS101 of the bacterial phytopathogen, Erwinia carotovora, makes the simple β-lactam antibiotic, 1-carbapen-2-em-3-carboxylic acid. We have mapped and sequenced the Erwinia genes encoding carbapenem production and have cloned these genes into Escherichia coli where we have reconstituted, for the first time, functional expression of the β-lactam in a heterologous host.

Analysis of bacterial carbapenem antibiotic production genes reveals a novel beta-lactam biosynthesis pathway.

Carbapenems are beta-lactam antibiotics which have an increasing utility in chemotherapy, particularly for nosocomial, multidrug-resistant infections. Strain GS101 of the bacterial phytopathogen, Erwinia carotovora, makes the simple beta-lactam antibiotic, 1-carbapen-2-em-3-carboxylic acid. We have mapped and sequenced the Erwinia genes encoding carbapenem production and have cloned these genes into Escherichia coli where we have reconstituted, for the first time, functional expression of the beta-lactam in a heterologous host.

Androgen receptor in human liver: characterization and quantitation in normal and diseased liver.

Liver is responsive to sex hormones. The role of androgens in normal human liver function is not well understood, although androgens have been implicated in several liver diseases. Because the human hepatic androgen receptor has not been adequately characterized, we analyzed cytosolic and nuclear fractions from normal human liver of both sexes for androgen-binding activity using multipoint saturation analysis with the androgenic radioligand methyltrienelone (R1881).

Effect of tamoxifen on hepatic regeneration in male rats.

A number of metabolic changes within the liver occur concurrent with hepatic regeneration. These processes suggest that the administration of an antiestrogen might alter the rate of hepatic regeneration. To examine this question, male Wistar rats were treated with tamoxifen (0.