Biomedical subjects

Gary Meyer

Publications and source records attributed to Gary Meyer.

7 recordsLinked to original sources

PubMed2005

Liquid chromatography-tandem mass spectrometry analysis of erythrocyte thiopurine nucleotides and effect of thiopurine methyltransferase gene variants on these metabolites in patients receiving azathioprine/6-mercaptopurine therapy.

BACKGROUND: Polymorphic thiopurine S-methyltransferase (TPMT) is a major determinant of thiopurine toxicity. METHODS: We extracted 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) from erythrocytes with perchloric acid and converted them to 6-thioguanine (6-TG) and a 6-methylmercaptopurine (6-MMP) derivative during a 60-min acid hydrolysis step. The liquid chromatography system consisted of a C(18) column with an ammonium acetate-formic acid-acetonitrile buffer. 8-Bromoadenine was the internal standard. Analytes were measured with positive ionization and multiple reaction monitoring mode. With PCR-restriction fragment length polymorphism analysis and TaqMan allelic discrimination, common TPMT alleles (*1, *2, *3A, *3B, *3C) were determined in 31 792 individuals. We used perchloric acid extraction, acid hydrolysis, and HPLC with ultraviolet detection to measure erythrocyte 6-TG and 6-MMP nucleotide concentrations in 6189 patients with inflammatory bowel disease receiving azathioprine/6-mercaptopurine therapy. RESULTS: Intra- and interday imprecision were <10% at low and high analyte concentrations. The conversion of 6-TG and 6-MMP nucleoside mono-, di-, and triphosphates was complete after hydrolysis. Allelic frequency for TPMT variant alleles ranged from 0.0063% (*3B) to 3.61% (*3A). Compared with wild types, TPMT heterozygotes had an 8.3-fold higher risk for 6-TGNs >450 pmol/8 x 10(8) erythrocytes (concentration associated with increased risk for leukopenia), but an 8.2-fold lower risk for 6-MMPNs >5700 pmol/8 x 10(8) erythrocytes (concentration associated with increased risk for hepatotoxicity). CONCLUSIONS: The liquid chromatography-tandem mass spectrometry method can be applied to the routine monitoring of thiopurine therapy. The association between TPMT genotype and metabolite concentrations illustrates the utility of pharmacogenetics in the management of patients undergoing treatment with thiopurines.

Adult↗

PubMed2005

An evaluation of the Freedom From Smoking Online cessation program among Wisconsin residents.

OBJECTIVE: To study the effectiveness of the American Lung Association's Freedom From Smoking Online cessation program in assisting Wisconsin residents to quit smoking. METHODS: Five hundred fifty-three Wisconsin residents who signed up for the American Lung Association's Freedom From Smoking Online cessation program over a 10-month period were solicited for participation. Of these, 80 individuals completed the initial survey (response rate 14.41%). Follow-up surveys were conducted 3, 6, 9, and 12 months after participants completed the program. Fifty-two participants completed the 3-month follow-up, 43 completed the 6-month follow-up, 38 completed the 9-month follow-up, and 36 completed the 12-month follow-up. RESULTS: Initial point prevalence rates or whether participants reported that they had smoked in the previous 24-hour period revealed a quit rate of 55%. Sustained abstinence or whether they reported that they had smoked in the previous 3-month period ranged between 28.8% (3 months after program completion) and 16.3% (1 year after program completion). CONCLUSION: Quit rates compare favorably to current clinic-based smoking cessation programs. Given the low cost nature of an on-line cessation program and the ability to reach a wide audience, the evaluation undertaken of the American Lung Association's Freedom From Smoking Online cessation program revealed promising results.

Adult↗

PubMed2004

Diffusion methodology: time to innovate?

Over the past 60 years, thousands of diffusion studies have been conducted in numerous disciplines of study including sociology, education, communication, marketing, and pubic health. With few exceptions, these studies have been driven by a methodological approach that has become institutionalized in diffusion research. This approach is characterized by the collection of quantitative data about one innovation gathered from adopters at a single point in time after widespread diffusion has occurred. This dominant approach is examined here in terms of both its strengths and weaknesses and with regard to its contribution to the collective base of understanding the diffusion of innovations. Alternative methodological approaches are proposed and reviewed with consideration for the means by which they may expand the knowledge base.

Diffusion of Innovation↗

PubMed2004

Contribution of common polymorphisms in reduced folate carrier and gamma-glutamylhydrolase to methotrexate polyglutamate levels in patients with rheumatoid arthritis.

We investigated whether polymorphisms in reduced folate carrier (SLC19A1 G80A) and gamma-glutamyl-hydrolase (GGH-401C/T) are predictive of methotrexate polyglutamate (MTXPG) levels in patients with rheumatoid arthritis treated with weekly low-dose methotrexate (MTX). Adult patients treated with MTX were enrolled in a multicentred study. Blood was drawn at the time of the visit, DNA was extracted and red blood cell (RBC) MTXPG levels (up to the penta-order of glutamation) were measured by high-performance liquid chromatography-fluorometry. A G80A polymorphism in SLC19A1 and a -401C/T promoter polymorphism in GGH were measured by polymerase chain reaction-restriction fragment length polymorphism. Multivariate linear and logistic regressions were used to predict long-chain RBC MTXPG3-5. In 226 adult patients receiving MTX (median 15 mg range: 5-25 mg) median RBC long-chain MTXPG3-5 was 56 nmol/l (range < 5-224 nmol/l). A total of 35 patients carried the SLC19A1 80AA genotype whereas 36 patients carried the GGH-401TT genotype. Weekly MTX dose, age, presence of the SLC19A1 80AA and GGH-401TT genotypes predicted independently and significantly MTXPG3-5 levels (global r = 0.38; P < 0.0001). Patients with the GGH-401TT genotype were 4.8-fold [odds ratio (OR) 95% confidence interval (CI) 1.8-13.0; P = 0.002] more likely to have MTXPG3-5 below the group median compared to patient carriers of the GGH-401CC or CT genotype. Conversely, those with the SLC19A1 80AA genotype were 3.4-fold more likely to have MTXPG3-5 levels above the group median compared to those with the SLC19A1 80GG or 80GA genotype (OR CI 95% 1.4-8.4; P = 0.007). These data demonstrate that polymorphisms in SLC19A1 and GGH affect polyglutamation of MTX.

Adult↗

PubMed2004

Assessing the Get Real about Violence curriculum: process and outcome evaluation results and implications.

Guided largely by the theory of reasoned action, the Get Real about Violence curriculum attempts to reduce verbal and physical aggression, as well as behaviors that encourage verbal or physical aggression, such as watching a fight and spreading rumors about a fight that is going to happen. This 12-lesson curriculum was evaluated using a pretest-posttest control group design. Participants were 293 seventh-grade boys and girls enrolled in two public junior high schools in a moderate size Midwestern city. The curriculum had its greatest effect on verbal aggression, where the experimental school outperformed the control school on three of four variables, including behavior, behavioral intent, and attitudes. The experimental school also outperformed the control school in several other instances, including intent to watch a fight, intent to spread rumors about a fight, and beliefs and opinions about fighting and violence in general. Implications for the Get Real about Violence curriculum, and for youth violence prevention and intervention programs are discussed.

Adolescent↗

PubMed2003

A radio-based approach to promoting gun safety: process and outcome evaluation implications and insights.

Three radio public service announcements (PSA) were created to increase knowledge of 10 gun-safety practices in a mid-Michigan county. Concurrently, a direct-mail coupon highlighting the same gun-safety practices was disseminated to over 70,000 households in the same county. Results of a telephone survey indicate that, compared to unexposed individuals, those who were exposed to the PSA were able to name significantly more gun-safety practices. Specifically, significant differences between those exposed to the PSA versus those not exposed were found for 5 gun-safety practices, as well as for a 4-item index measuring gun locking and storage behaviors, and a 9-item index that included all gun-safety practices.

Firearms↗

PubMed2002

Signaling mechanisms that regulate actin-based motility processes in the nervous system.

Actin-based motility is critical for nervous system development. Both the migration of neurons and the extension of neurites require organized actin polymerization to push the cell membrane forward. Numerous extracellular stimulants of motility and axon guidance cues regulate actin-based motility through the rho GTPases (rho, rac, and cdc42). The rho GTPases reorganize the actin cytoskeleton, leading to stress fiber, filopodium, or lamellipodium formation. The activity of the rho GTPases is regulated by a variety of proteins that either stimulate GTP uptake (activation) or hydrolysis (inactivation). These proteins potentially link extracellular signals to the activation state of rho GTPases. Effectors downstream of the rho GTPases that directly influence actin polymerization have been identified and are involved in neurite development. The Arp2/3 complex nucleates the formation of new actin branches that extend the membrane forward. Ena/VASP proteins can cause the formation of longer actin filaments, characteristic of growth cone actin morphology, by preventing the capping of barbed ends. Actin-depolymerizing factor (ADF)/cofilin depolymerizes and severs actin branches in older parts of the actin meshwork, freeing monomers to be re-incorporated into actively growing filaments. The signaling mechanisms by which extracellular cues that guide axons to their targets lead to direct effects on actin filament dynamics are becoming better understood.

Actins↗