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Michael Gill

Publications and source records attributed to Michael Gill.

44 records · Page 3Linked to original sources
PubMed2002

Validation of a liquid chromatographic method for the determination of ibuprofen in human plasma.

A simple, rapid method of determining the ibuprofen concentration in small volumes of human plasma (50 microl) by HPLC was developed. The sample was prepared for injection using a solid-phase extraction method, with naproxen as the internal standard. A 96-well extraction plate was used, easing sample preparation and allowing the simultaneous extraction of multiple plasma samples directly into the HPLC injection vials. Samples were stable at room temperature for at least 48 h prior to injection. The HPLC method used an ultraviolet detector with a 5-min run time and measured concentrations across the range typically seen with the clinical use of this drug. The calibration curve was linear across the concentration range of 0.78-100 microg/ml with a limit of quantitation (LOQ) of 1.56 microg/ml. The coefficient of variation for intra-day and inter-day precision was 6% or less with accuracies within 2% of the nominal values for low (4.5 microg/ml), medium (40 microg/ml) and high (85 microg/ml) ibuprofen concentrations. For ibuprofen concentrations at the LOQ, the intra-day and inter-day precision and accuracy were within 10 and 15%, respectively. Recovery was 87% or greater for ibuprofen. This method was used to analyze plasma samples for unknown ibuprofen concentrations in bioequivalence and limited food effect studies of different formulations of ibuprofen. Thus, this method has been fully validated and used in the analysis of unknown plasma samples for ibuprofen.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Association of DRD4 in children with ADHD and comorbid conduct problems.

Recent family and twin study findings suggest that ADHD when comorbid with conduct problems may represent a particularly familial and heritable form of ADHD. Although several independent groups have shown association between the DRD4 7 repeat allele and ADHD, others have failed to replicate this finding. Previous TDT analyses of UK and Eire samples had also been negative. We set out to further examine the role of DRD4 but selecting a subgroup of children with ADHD and comorbid conduct problems. Families were recruited from Manchester, Ireland, Birmingham and London clinics. From these, 67 children who fulfilled diagnostic criteria for ADHD and who displayed conduct disorder symptoms were selected. TDT analysis, which had previously yielded negative results for the total sample, showed evidence of association between DRD4 and "ADHD with conduct problems" (7 repeat allele-24 transmissions, 13 non-transmissions; one-tailed P=0.05). These results provide further support for the role of DRD4 in ADHD. Furthermore, these results when considered together with family and twin study findings, suggest that those children with ADHD and comorbid conduct problems may be particularly informative for molecular genetic studies of ADHD. Further work is needed to examine these phenotype issues.

Adolescent↗
PubMed2002

Dopaminergic system genes in ADHD: toward a biological hypothesis.

Converging evidence has implicated abnormalities of dopamine neurotransmission to the pathology of attention deficit hyperactivity disorder (ADHD). Several genetic association studies have been published, but so far, no DNA variants have been unequivocally demonstrated as contributing to ADHD susceptibility. Four dopamine related gene loci have been implicated, however: DAT 1, DRD 4, DBH, and DRD 5. Each of these may influence the liability of ADHD to a small degree. Notably, all are involved in signal transduction at the neuronal synapse. In this article, we investigate as candidate genes for ADHD, DNA polymorphisms at dopamine receptors, the dopamine transporter, and genes known to be involved in dopamine synthesis and metabolism. In a recent article, we confirmed the previously reported association of DAT 1 (480 bp allele) with ADHD and identified polymorphisms at two additional loci showing preferential transmission to ADHD children of alleles at DRD 5 (148 bp allele) and at DBH (allele 2, Taq I polymorphism). Increased transmission of the 4 bp deletion in the untranslated exon 1 of the DOPA decarboxylase gene was also observed but was of marginal significance. Nonsignificant trends of association were found for TH (allele 2) and DRD2 (Ser-311). No preferential transmission of alleles to ADHD children was observed for polymorphisms at DRD 1, DRD 2 (Taq I), DRD 3, DRD 4, and COMT. Analyzing the data by sex of transmitting parent showed significant preferential paternal transmission of alleles at TH (allele 2) and a nonsignificant trend for paternal transmission for DRD 2 (Ser-311). We attempt to put these findings together with what is known of the function of the particular proteins, and suggest working hypotheses.

Adolescent↗
PubMed2002

Are patients with bipolar affective disorder socially disadvantaged? A comparison with a control group.

BACKGROUND: Bipolar affective disorder (BPAD) has considerable implications for personal and social functioning. However a tendency to be over-represented in high socio-economic classes has been reported in earlier studies, suggesting that social disadvantage accompanying the illness is not severe. In addition, an association between affective disorders in general and increased residential mobility has been suggested, but it is unclear if such an association exists with BPAD. OBJECTIVES: (1) To investigate the suggestion made in previous studies that patients with bipolar disorder are advantaged socially. (2) To test the hypothesis that patients with bipolar disorder show greater residential mobility compared with other patients with psychiatric disorders. METHODS: Ninety patients with DSM IV diagnosis of bipolar disorder admitted to the acute in-patient unit of a public-financed district psychiatric service in Dublin were compared with a control group of 91 randomly selected patients with other psychiatric diagnoses, excluding schizophrenia. Socio-economic, educational and employment ratings were compared, and also duration of illness, frequency of admission and residential mobility. The data were collected retrospectively from case notes and through semistructured interviews with patients or their relatives. The bipolar group was compared with the control group and to the unipolar depression subgroup. RESULTS: The bipolar and control groups were found to have similar demographic and socio-economic features, although the bipolar group had more years of education compared with the whole control group but not when compared with the unipolar depression group. The bipolar group showed longer duration of psychiatric disorder, more frequent hospital admissions and more frequent residential moves since the onset of the illness. CONCLUSION: Bipolar patients requiring in-patient care in this service experience severe disruption to their lives over prolonged periods.

Adult↗
PubMed2002

Transgenic Drosophila reveals a functional in vivo receptor for the Bacillus thuringiensis toxin Cry1Ac1.

The bacterium Bacillus thuringiensis synthesizes toxins (delta-endotoxins) that are highly specific for insects. Once ingested, the activated form of the toxin binds to a specific receptor(s) located on the midgut epithelial cells, inserts into the membrane causing the formation of leakage pores and eventual death of the susceptible insect larvae. Manduca sexta larvae are highly susceptible to Cry1Ac1, a toxin that is believed to bind M. sexta Aminopeptidase N, a glycoprotein located on the apical membrane. However, the binding data obtained to date only support the interaction of Cry1Ac1 with APN in vitro. To explore the in vivo role of APN, we have utilized the GAL4 enhancer trap technique to drive the expression of M. sexta APN in both midgut and mesodermal tissues of Cry1Ac1 insensitive Drosophila larvae. Transgenic Drosophila fed the toxin were now killed, demonstrating that APN can function as a receptor for Cry1Ac1 in vivo.

Animals↗
PubMed2002

Impact of current good manufacturing practices and emission regulations and guidances on the discharge of pharmaceutical chemicals into the environment from manufacturing, use, and disposal.

The current Good Manufacturing Practice (cGMP) and effluent emission (use and disposal) regulations of the U.S. Food and Drug Administration (FDA) and manufacturing effluent discharge and emission regulations of the U.S. Environmental Protection Agency (U.S. EPA) require contained manufacture, use, and disposal of pharmaceuticals with the goal of minimizing the release of pharmaceutical chemicals into the environment. However, debate has recently arisen in several scientific forums over whether these regulations adequately protect human and environmental health from the new pharmaceutical drugs introduced each year into the marketplace and the multitude of existing products, each with many distinct biochemical modes of actions. To address this issue, it is important to understand the relevance of current cGMP regulations and emission regulations that have a direct bearing on the releases of pharmaceutical chemicals into the environment during the manufacture, use, and disposal of active pharmaceutical ingredients (drug substances) and drug products. This knowledge may help us assess the quantity of residues that may be released into the environment. Additionally, the information on physical, chemical, and degradation and sorption properties of the pharmaceutical chemicals may help determine the net residue levels that could persist in the environment to evaluate if such residues have any bearing on human and environmental health. The scientific and regulatory aspects of issues related to the manufacture, use, and disposal of pharmaceutical chemicals are discussed in this article, with special emphasis on potential environmental exposure pathways during the life cycle of an active pharmaceutical ingredient or drug product. The mechanisms of degradation (transformation or depletion) and dilution of pharmaceutical residues that may be released into aquatic or terrestrial environmental compartments are described. Such degradation and dilution of pharmaceutical chemicals in the environment may significantly reduce the residues. It is important to evaluate whether such residue levels have any measurable impact on human and/or environmental health.

Drug Industry↗