Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis.

Background: Platelet activating factor (PAF) is believed to amplify the activity of key mediators of the systemic inflammatory response syndrome (SIRS) in acute pancreatitis, resulting in multiorgan dysfunction syndrome. We tested the hypothesis that a potent PAF antagonist, lexipafant, could dampen SIRS and reduce organ failure in severe acute pancreatitis.

Methods: We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6.

Specific patterns of chromosomal abnormalities are associated with RER status in sporadic colorectal cancer.

Current opinion of the genetic events driving colorectal tumourigenesis focuses on genomic instability. At least two apparently independent mechanisms are recognized, microsatellite instability and chromosomal instability. The genetic defects underlying each type of instability are only partially understood and controversy remains as to the role of p53 in the generation of chromosomal defects in colorectal cancer.

Indoor air quality in a middle school, Part II: Development of emission factors for particulate matter and bioaerosols.

A middle school (grades 6 to 8) in a residential section of Springfield, Illinois, with no known air quality problems, was selected for a baseline indoor air quality survey. The study was designed to measure and evaluate air quality at the middle school with the objective of providing a benchmark for comparisons with measurements in schools with potential air quality problems. The focus of this article is on the development of emission factors for particulate matter and bioaerosols.

Conjugated linoleic acid suppresses triglyceride accumulation and induces apoptosis in 3T3-L1 preadipocytes.

Four sets of experiments were conducted to examine the influence of conjugated linoleic acid (CLA) isomers during proliferation and differentiation of cultures of 3T3-L1 preadipocytes using physiological culturing conditions. Cultures treated with either albumin [bovine serum albumin (BSA) vehicle] or linoleic acid (LA) served as controls. For the proliferation study (Expt.

Association of asthma symptoms and severity with indoor bioaerosols.

Background: In this study, repeated measurements were made of levels of mold spores, bacteria, and dust-mite allergens over a 7-month period in the homes of asthmatics, and relationships with measures of asthma severity were evaluated.

Methods: A sample of 57 asthmatic individuals, living in 44 homes in East Moline, Illinois, and nearby communities, participated in a panel study. The homes were visited up to nine times during the study to collect air and dust samples.

Dieldrin induces cytosolic [3H]7, 12-dimethylbenz[a]anthracene binding but not multidrug resistance proteins in rainbow trout liver.

Previously it was demonstrated that biliary excretion of a single dose of [14C]dieldrin or [3H]7, 12-dimethylbenz/alanthracene (DMBA) was stimulated up to 700% and 300%, respectively, in rainbow trout fed 0.3-0.4 mg dieldrin/kg/d for 9-12 wk.

Racial differences in symptoms and complications in adults with type 2 diabetes mellitus.

Objective: To compare the frequency of common symptoms and complications between African- and white American adults with type 2 diabetes mellitus in a primary care setting, and to examine associations of these conditions with glycemic control.

Design: Three hundred and four adults with type 2 diabetes participated in this cross-sectional analysis; 142 of whom were African-Americans. Patients were recruited from a family practice ambulatory care unit and a community health center.

Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis.

Heme oxygenase-1 (HO-1) is a 32-kDa microsomal enzyme that catalyzes the conversion of heme to biliverdin, releasing iron and carbon monoxide. Induction of HO-1 occurs as a protective response in cells/tissues exposed to a wide variety of oxidant stimuli. The chemotherapeutic effects of cis-diamminedichloroplatinum(II) (cisplatin), a commonly used anticancer drug, are limited by significant nephrotoxicity, which is characterized by varying degrees of renal tubular apoptosis and necrosis.

A new look at the neuronal nicotinic acetylcholine receptor pharmacophore.

Interest in the field of nicotinic receptors has been recently stimulated both by the discovery of the potential therapeutic effects of new agonists, and by the discovery of an association between nicotinic receptor mutations and human neurological diseases. Expression of human receptors in an exogenous system allows their study in isolation. Receptors reconstituted by pairwise injection of either alpha4 or alpha3 with beta2 or beta4 subunits displayed important differences between the resulting receptor subtypes.

Salmonid sexual development is not consistently altered by embryonic exposure to endocrine-active chemicals.

Fish sexual development is sensitive to exogenous hormone manipulation, and salmonids have been used extensively as environmental sentinels and models for biomedical research. We simulated maternal transfer of contaminants by microinjecting rainbow trout (Oncorhynchus mykiss) and chinook salmon (Oncorhynchus tshawytscha) embryos. Fish were reared for 6 months and sexed, and gonads were removed for histology and measurement of in vitro steroid production.

A double-blind placebo-controlled study of an infusion of lexipafant (Platelet-activating factor receptor antagonist) in patients with severe sepsis.

Platelet-activating factor (PAF) is a potent endogenous proinflammatory mediator implicated in the pathogenesis of septic shock. A double-blind randomized placebo-controlled trial of an intravenous PAF receptor antagonist (lexipafant) was conducted with 131 adult Thai patients with suspected severe sepsis (66 of whom had positive blood cultures). Detailed serial clinical, biochemical, and cytokine measurements were performed.

Heterogeneity studies identify a subset of sporadic colorectal cancers without evidence for chromosomal or microsatellite instability.

Two apparently independent mechanisms of instability are recognized in colorectal cancer, microsatellite instability and chromosomal instability. Evidence from colorectal cancer cell lines indicates the presence of either, or both, types of instability in the vast majority. Here, we sought to determine the prevalence of such instability in primary sporadic colorectal cancers.

Chicago community-based asthma intervention trial: feasibility of delivering peer education in an inner-city population.

The most effective means of educating children with asthma and their families has not been clearly demonstrated in previous studies. Peer education is uniquely suited to the complex problems encountered in underserved populations. The purpose of this study was to show the feasibility of delivering a peer education program for children with asthma and the effect of the program on indoor allergen levels in an inner-city population in Chicago.

Predictors of patient-reported physical and mental health 6 months after percutaneous coronary revascularization.

Background: There is interest in measuring and comparing outcomes of percutaneous transluminal coronary angioplasty (PTCA) other than death, but there are no accepted methods for adjusting these outcomes for preprocedure differences in populations. We sought to identify independent predictors of functional outcome after PTCA.

Methods And Results: We developed multivariate risk adjustment models for the 6-month postprocedure physical and mental health summary scores of the MOS SF-36.

Apoptosis and carcinogenesis.

Apoptosis has long been known to be effected through a common sequence of structural changes, despite the wide variety of initiating stimuli. These common structural events appear to depend upon activation of a set of enzymes (caspases) which direct a strongly conserved, terminal effector pathway. The regulation of this pathway, and in particular its coupling to DNA damage, appears to be critical in maintaining at low levels the number of mutated cells within tissues.

Trematode accumulation by the estuarine gastropod Ilyanassa obsoleta.

The accumulation of larval trematodes by Ilyanassa obsoleta (Gastropoda) at 2 estuarine sites in Delaware was studied. Initial infection status of snails was assayed by looking for shed cercariae. Native snails (most already infected) were deployed at sites A and B, and sentinel snails (putatively uninfected) were deployed at site B.

Role of BAX mutations in mismatch repair-deficient colorectal carcinogenesis.

BAX gene mutations occur in approximately 50% of RER+ colorectal cancers. To determine the role of these mutations in tumour progression we analysed multiple different tumour sites from RER+ colorectal cancers for BAX mutations. Sixty colorectal carcinomas were analysed for microsatellite instability at loci BAT-26, L-myc, TGF betaRII, D13S160 and D2S123.

No evidence for linkage between schizophrenia and markers at chromosome 15q13-14.

Freedman et al. [1997: Proc Natl Acad Sci USA 94:587-592] reported linkage in nine multiplex schizophrenia families to markers on chromosome 15, using impaired neuronal inhibition to repeated auditory stimuli (P50), a neurophysiological deficit associated with schizophrenia, as the phenotype. The highest LOD score obtained (5.

Distribution of Na,K-ATPase is normal in the inner ear of a mouse with a null mutation of the glucocorticoid receptor.

This study was performed in order to test the hypothesis that the glucocorticoid hormone stimulates the formation of Na,K-ATPase in the inner ear of the mouse. An immunohistochemical study with respect to the presence and distribution of glucocorticoid receptors (GR) and Na,K-ATPase in the vestibular and cochlear regions of the inner ear was performed on a C57BL mouse with a null mutation of the glucocorticoid receptor (GR mutant mouse). The wild type C57BL mouse and the CBA mouse served as normal controls.

Amplification of DNA sequences from chromosome 19q13.1 in human pancreatic cell lines.

Conventional cytogenetics and comparative genomic hybridization (CGH) were utilized to identify recurrent chromosomal imbalances in 12 pancreatic adenocarcinoma cell lines. Multiple deletions and gains were observed in all cell lines. Losses affecting chromosomes or chromosome arms 9p, 13, 18q, 8p, 4, and 10p and gains involving chromosome arms or bands 19q13.

Reported alcohol consumption and the serum carbohydrate-deficient transferrin test in third-year medical students.

The serum carbohydrate-deficient transferrin (CDT) test was performed on 143 third-year medical students along with questionnaires for the self-reporting of alcohol consumption during the last 2 weeks, the last 6 months, and questions on any alcohol-related untoward events. We found that the CDT test has poor sensitivity for detecting binge drinking in our population of students, despite some likely under-reporting of drinking. Self-reporting of drinking is commonly unreliable, and we found no significant correlation between the CDT concentrations in serum and the magnitude of self-reported alcohol use during 2-week and 6-month periods.

A potential role for glucagon in the treatment of drug-induced symptomatic bradycardia.

Nine cases of symptomatic bradycardia are presented in which treatment with intravenous glucagon was administered when atropine failed to improve the patient's condition significantly. Although the cause often was not obvious at presentation, all nine subjects took oral medications that could have contributed to the development of symptomatic bradycardia. Eight of nine patients demonstrated clinical improvement 5 to 10 min after glucagon administration, which was consistent with its peak clinical action.

Modulation of 7,12-dimethylbenz[a]anthracene disposition and hepatocarcinogenesis by dieldrin and chlordecone in rainbow trout.

The present study examined whether modified xenobiotic transport, resulting from chlordecone (CD) or dieldrin pretreatment, would alter polycyclic aromatic hydrocarbon (PAH) or organochlorine (OC) target organ doses and subsequent tumor organospecificity or incidence rates in rainbow trout. Additionally, the potential for exposure to dieldrin or CD, following PAH exposure, to enhance tumor incidence was assessed. Evaluation of CD pretreatment effects on [14C]CD disposition in trout was conducted following two i.

Interaction of 2,2',4,4',5,5'-hexachlorobiphenyl with hepatic cytochrome P-4501A in rainbow trout (Oncorhynchus mykiss).

Di-ortho polychlorinated biphenyls (PCBs) are prominent environmental contaminants and their biological activity in fish may be more significant than previously thought. Four weeks after intraperitoneal (i.p.