Field evaluation of low-dose warfarin baits to control wild pigs (Sus scrofa) in North Texas.

Wild pigs (Sus scrofa) are a highly detrimental invasive species that occupy a rapidly expanding range within the United States. In Australia, field trials evaluating baits containing 0.09% warfarin resulted in wild pig population reduction >95%.

Characterisation of the HLA-DRB1*07:01 biomarker for lapatinib-induced liver toxicity during treatment of early-stage breast cancer patients with lapatinib in combination with trastuzumab and/or taxanes.

HLA-DRB1*07:01 allele carriage was characterised as a risk biomarker for lapatinib-induced liver injury in a large global study evaluating lapatinib, alone and in combination with trastuzumab and taxanes, as adjuvant therapy for advanced breast cancer (adjuvant lapatinib and/or trastuzumab treatment optimisation). HLA-DRB1*07:01 carriage was associated with serum alanine aminotransferase (ALT) elevations in lapatinib-treated patients (odds ratio 6.5, P=3 × 10, n=4482) and the risk and severity of ALT elevation for lapatinib-treated patients was higher in homozygous than heterozygous HLA-DRB1*07:01 genotype carriers.

Phlebotomine sandfly ecology on the Indian subcontinent: does village vegetation play a role in sandfly distribution in Bihar, India?

Visceral leishmaniasis (VL) is a disease that results in approximately 50 000 human deaths annually. It is transmitted through the bites of phlebotomine sandflies and around two-thirds of cases occur on the Indian subcontinent. Indoor residual spraying (IRS), the efficacy of which depends upon sandfly adults resting indoors, is the only sandfly control method used in India.

Effect of lapatinib on oral digoxin absorption in patients.

The potential for an interaction between lapatinib and absorption of the P-glycoprotein (ABCB1) substrate digoxin at a therapeutic dose in breast cancer patients was characterized. Seventeen women with HER2-positive metastatic breast cancer received a single oral 0.5-mg dose of digoxin on days 1 and 9 and oral lapatinib 1500 mg once daily on days 2 through 9.

Pyrexia in dabrafenib-treated melanoma patients is not associated with common genetic variation or HLA polymorphisms.

Aim: Pyrexia is a common adverse event (AE) on dabrafenib treatment (monotherapy or combination with trametinib). Since germline SNPs and HLA alleles are implicated in drug-induced AEs, this study investigated their association with pyrexia.

Patients & Methods: 1006 melanoma subjects from five dabrafenib-trametinib clinical studies underwent genotyping for genome-wide SNPs, which enabled imputation of 150 HLA alleles.

HLA-B*57:01 Confers Susceptibility to Pazopanib-Associated Liver Injury in Patients with Cancer.

Purpose: Pazopanib is an effective treatment for advanced renal cell carcinoma and soft-tissue sarcoma. Transaminase elevations have been commonly observed in pazopanib-treated patients. We conducted pharmacogenetic analyses to explore mechanistic insight into pazopanib-induced liver injury.

Rash in lapatinib-treated patients is not associated with human leukocyte antigen polymorphisms.

Rash is a common side effect of lapatinib treatment. Since human leukocyte antigen (HLA) alleles have been implicated in multiple drug-induced cutaneous reactions, this study investigated the association of HLA alleles with lapatinib-induced rash. 1191 participants from a large lapatinib monotherapy trial underwent HLA genotyping, and allele carriage frequencies between rash cases and controls were compared.

Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01.

Lapatinib is associated with a low incidence of serious liver injury. Previous investigations have identified and confirmed the Class II allele HLA-DRB1*07:01 to be strongly associated with lapatinib-induced liver injury; however, the moderate positive predictive value limits its clinical utility. To assess whether additional genetic variants located within the major histocompatibility complex locus or elsewhere in the genome may influence lapatinib-induced liver injury risk, and potentially lead to a genetic association with improved predictive qualities, we have taken two approaches: a genome-wide association study and a whole-genome sequencing study.

National survey of physicians' perception of the cause, complications, and management of gastroparesis.

Objectives: Manifestations of gastroparesis are heterogeneous and clinical complications are poorly defined. Misconceptions of gastroparesis may be common. The objective was to determine physicians' perception of gastroparesis and identify areas that need further research and education.

HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer.

Purpose: Hepatobiliary adverse events (AEs) have been observed in a small proportion of patients with metastatic breast cancer (MBC) treated with lapatinib. This study sought to identify gene variants associated with lapatinib-induced ALT elevation and hepatobiliary AEs.

Patients And Methods: A two-stage pharmacogenetic investigation of ALT elevation was conducted in lapatinib-treated patients with MBC.

The Population Reference Sample, POPRES: a resource for population, disease, and pharmacological genetics research.

Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections.

Death or hospitalization of patients on chronic hemodialysis is associated with a physician-based diagnosis of depression.

Depressive symptoms, assessed using a self-report type of questionnaire, have been associated with poor outcomes in dialysis patients. Here we determined if depressive disorders diagnosed by physicians are also associated with such outcomes. Ninety-eight consecutive patients on chronic hemodialysis underwent the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders administered by a physician.

Cutaneous mastocytosis: a review focusing on the pediatric population.

Cutaneous mastocytosis can be divided into 4 different clinical variants--urticaria pigmentosa, solitary mastocytoma, diffuse cutaneous mastocytosis, and telangiectasia macularis eruptiva perstans. Skin findings are often accompanied by symptoms secondary to mast cell release of mediators. These symptoms can be both localized to the skin lesion and systemic because of the release of mediators into the bloodstream.

Mortality, kidney disease and cardiac procedures following acute coronary syndrome.

Background: Cardiac interventions are underutilized in patients with chronic kidney disease (CKD) following acute coronary syndrome (ACS) partly due to nephrotoxicity concerns.

Methods: We analyzed outcomes of 4631 subjects with ACS enrolled in the Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion trial, including time to death, time to reduced renal function (50% reduction in estimated glomerular filtration rate (eGFR) or development of end-stage renal disease (ESRD)) and percent change in eGFR from baseline.

Results: Subjects with a lower baseline eGFR were more likely to be older, female and have diabetes, hypertension, congestive heart failure or peripheral vascular disease (all P < 0.

Risk for cardiovascular outcomes among subjects with atherosclerotic cardiovascular disease and greater-than-normal estimated glomerular filtration rate.

Background And Objectives: Estimating equations for calculating glomerular filtration rate (eGFR) occasionally identify patients with elevated eGFR, yet the prognostic significance remains to be determined. This study sought to define the association of an elevated eGFR on the risk for death and cardiovascular outcomes among subjects with atherosclerotic cardiovascular disease.

Design, Setting, Participants, & Measurements: Data from 8941 subjects who had a history of atherosclerotic vascular disease and were enrolled in the Blockade of the Glycoprotein IIb/IIIa Receptor to Avoid Vascular Occlusion trial were analyzed.

Mortality by dialysis modality among patients who have end-stage renal disease and are awaiting renal transplantation.

Comparing outcomes related to dialysis modality is complicated by selection bias introduced by patients and physicians. To address the impact of selection bias, this study compared mortality by initial dialysis modality among patients who had ESRD and were placed on the transplant waiting list. This study was a historical prospective cohort of 12,568 patients in the United States who initiated dialysis between May 1, 1995, and October 31, 1998, and were placed on the transplant waiting list before dialysis initiation.

Leptin and renal disease.

Leptin is a mediator of metabolism and disease in a variety of organ systems, most notably as an agent of energy stores. However, its role in renal disease as an inflammatory agent as well as its potential impact on the cachexia of uremia have sparked new interest in the molecule for nephrologists. This review elucidates the complex uremic state, the historical discovery of leptin and its physiology, and the potential interactions leptin has on both the progression of kidney disease as well as the morbidity and mortality of end-stage renal disease.

Case-control single-marker and haplotypic association analysis of pedigree data.

Related individuals collected for use in linkage studies may be used in case-control linkage disequilibrium analysis, provided one takes into account correlations between individuals due to identity-by-descent (IBD) sharing. We account for these correlations by calculating a weight for each individual. The weights are used in constructing a composite likelihood, which is maximized iteratively to form likelihood ratio tests for single-marker and haplotypic associations.

Analysis of a clonal selection event during transposon-mediated nested-deletion formation in rare BAC and PAC clones.

Nested deletions from one end of the genomic DNA in bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs) are readily generated by inserting a loxP site-containing Tn10 minitransposon into the recombinant clone and transducing with P1 phage. Although the size of clones in the deletion series is largely random, in about 5% of BACs and PACs the distribution appears skewed to a certain length, and in rare cases (<1%) is definitely skewed to a particular size. Here we investigate this relatively rare phenomenon and validate that sequence-specific transposon insertions are not the cause of such skewed nested-deletion libraries.

Genomewide search for type 2 diabetes susceptibility genes in four American populations.

Type 2 diabetes is a serious, genetically influenced disease for which no fully effective treatments are available. Identification of biochemical or regulatory pathways involved in the disease syndrome could lead to innovative therapeutic interventions. One way to identify such pathways is the genetic analysis of families with multiple affected members where disease predisposing genes are likely to be segregating.

Defective bypass replication of a leading strand cyclobutane thymine dimer in xeroderma pigmentosum variant cell extracts.

Xeroderma pigmentosum variant (XP-V) is an inherited disorder resulting in hypersensitivity to the cytotoxic, mutagenic, and carcinogenic effects of UV light. There is evidence suggesting that XP-V cells carry a defect in the replication of UV-induced DNA damage, leading to mutations in genes, e.g.

Biochemical characteristics of endonuclease activity within the nucleotidyl DNA excision repair pathway of permeable human fibroblasts.

DNA strand breage in response to damage produced by UV (254 nm) radiation was characterized after permeabilization of diploid normal and xeroderma pigmentosum variant fibroblasts. The breakage reaction required ATP, Mg2+ and sucrose for maximal activity and was inhibited by 150 mM Na+ or K+ and 1 mM N-ethylmaleimide. ATP-dependent strand breakage was saturated at UV fluences of above 10 J/m2 and in the presence of DNA precursors breakage was rapidly followed by DNA polymerase and ligase activities to seal the strand breaks.

Reparative strand incision in saponin-permeabilized human fibroblasts.

The damage-directed strand incision step in the nucleotidyl DNA excision-repair pathway (NDERP) was characterized in quiescent monolayer cultures of human fibroblasts in which the plasma membrane was selectively permeabilized with saponin. When permeable normal human fibroblasts (NHF) were incubated in a DNA-repair assay mixture lacking the deoxyribonucleoside triphosphate precursors, the numbers of UV-dependent DNA-strand breaks were increased by about 9-fold consistent with the uncoupling of incision from gap-filling DNA synthesis and ligation. In uncoupled NHF omission of ATP reduced the numbers of UV-dependent strand breaks by 84% confirming the requirement for ATP for reparative strand incision.