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Biomedical subjects

F Patterson

Publications and source records attributed to F Patterson.

17 recordsLinked to original sources
PubMed2006

Association of OPRM1 A118G variant with the relative reinforcing value of nicotine.

RATIONALE: The endogenous opioid system has been implicated in substance abuse and response to pharmacotherapies for nicotine and alcohol addiction. We examined (1) the association of the functional OPRM1 A118G variant with the relative reinforcing value of nicotine and (2) the main and interacting effects of the mu-opioid receptor antagonist naltrexone on nicotine reinforcement. METHODS: In a within-subject, double-blind human laboratory study, 30 smokers of each OPRM1 genotype (A/A vs. A/G or G/G) participated in two experimental sessions following 4 days of orally administered naltrexone 50 mg or placebo. Participants completed a validated assessment of the relative reinforcing value of nicotine. This cigarette choice paradigm assesses self-administration of 0.6 mg nicotine vs. 0.05 mg (denicotinized) cigarettes after a brief period of nicotine abstinence. RESULTS: The relative reinforcing value of nicotine (number of nicotine cigarette puffs) was predicted by a significant OPRM1 by gender interaction. Among women, the low-activity G allele (A/G and G/G) was associated with a reduced reinforcing value of nicotine; among male smokers, there was no association with genotype. Smokers carrying a G allele were also significantly less likely to differentiate the nicotine vs. denicotinized cigarettes by subjective ratings of satisfaction and strength. No evidence for an effect of naltrexone on nicotine reinforcement was found in the overall sample or in the genotype or gender subgroups. CONCLUSIONS: This study provides initial evidence for an association of the OPRM1 A118G variant with nicotine reinforcement in women.

Adaptation, Psychological↗
PubMed2006

Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy.

We investigated the effect of slow metabolism of nicotine, predicted by CYP2A6 genotypes resulting in less than or equal to 50% activity, on baseline smoking behaviours and treatment variables in an open-label nicotine replacement therapy (NRT) clinical trial. Caucasian smokers with CYP2A6 slow vs normal metabolism had lower metabolic activity, indicated by the 3-hydroxycotinine/cotinine ratio (0.23+/-0.17 vs 0.45+/-0.22, P<0.01, respectively). CYP2A6 slow metabolizers also smoked fewer cigarettes per day compared to normal metabolizers (20+/-7 vs 24+/-10, respectively, P<0.04). With nicotine patch use, slow metabolizers had higher nicotine plasma levels compared to normal metabolizers (22.8+/-4.6 vs 15.8+/-7.6 ng/ml, respectively, P=0.02) while using the same numbers of patches/week. With nicotine spray use, where like in smoking the nicotine intake can be easily adjusted to adapt to rates of metabolism, slow metabolizers achieved similar nicotine levels compared to normal metabolizers (5.8+/-4.1 vs 8.0+/-9.1 ng/ml, P=0.82), by using fewer doses of nicotine spray/day (4.8+/-3.6 vs 10.5+/-8.0, respectively, P<0.02). These findings indicate that CYP2A6 genotype influences smoking behaviour in a Caucasian treatment-seeking population and that CYP2A6 genotype affects plasma levels obtained from, and usage of, NRT.

Administration, Cutaneous↗
PubMed2006

Selecting doctors for postgraduate training in paediatrics using a competency based assessment centre.

The design and implementation of an assessment centre in the South Yorkshire and South Humberside deanery for selecting doctors into postgraduate training in paediatric medicine is described. Eleven competency domains were identified in the job analysis. An assessment centre comprising of four exercises was implemented to assess candidates. There were modest relationships between candidates' performance on the various assessment centre exercises. Outcomes based on interview performance were related to, but not the same as, outcomes based on the combined results of the three other assessment centre exercises. Candidates perceived the assessment centre to be a fair selection method. It is concluded that an assessment centre approach to SHO recruitment is feasible and provides a greater breadth and depth of information about candidates than does a structured interview.

Chi-Square Distribution↗
PubMed2004

The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial.

To determine whether the functional mu-opioid receptor (OPRM1) Asn40Asp variant predicts the comparative efficacy of different forms of NRT, we conducted a clinical trial of transdermal nicotine (TN) vs nicotine nasal spray (NS) in 320 smokers of European ancestry. Smokers carrying the OPRM1 Asp40 variant (n=82) were significantly more likely than those homozygous for the Asn40 variant (n=238) to be abstinent at the end of treatment, and reported less mood disturbance and weight gain. The genotype effect on treatment outcome was most pronounced among smokers receiving TN, particularly during the 21 mg dose phase. Smokers who carry the OPRM1 Asp40 variant are likely to have a favorable response to TN and may benefit from extended therapy with the 21 mg dose.

Administration, Cutaneous↗
PubMed2003

Alveolar soft part sarcoma--reciprocal translocation between chromosome 17q25 and Xp11. Report of a case with metastases at presentation and review of the literature.

The molecular pathogenesis of alveolar soft part sarcoma, a rare tumor with uncertain histogenesis, was elucidated recently and was shown to be due to a translocation between chromosome 17q25 and Xp11 resulting in a fusion product between TFE3 (a transcription factor gene) at chromosome Xp11 and a novel gene designated as ASPL at chromosome 17q25. This results in the transcriptional dysregulation in the pathogenesis of this neoplasm. Of the 12 cases reported so far, the translocation was due to non-reciprocal translocation in 11 cases with only one case demonstrating a reciprocal translocation with respective fusion products. We report yet another case with reciprocal translocation between chromosomes 17q25 and Xp11 with TFE3/ASPL fusion product who presented with metastatic disease. A standard cytogenetic analysis of primary tumor cells with G-banding revealed an abnormal karyotype: 46, X, t(X;17)(p11;q25)[15]/46,XX[5]. PCR analysis of the frozen tumor tissue revealed a type 1 fusion product as described in the literature. We demonstrate a rare cytogenetic abnormality in ASPS, namely reciprocal translocation between chromosomes 17q25 and Xp11 with demonstration of molecular fusion product between TFE3 and ASPL in a patient who initially presented with pulmonary metastases.

Adult↗
PubMed2000

A competency model for general practice: implications for selection, training, and development.

BACKGROUND: The role of the general practitioner (GP) has changed significantly over the past decade. This problem is compounded by growing concern over postgraduate attrition rates from medicine, with current estimates as high as 19%. AIM: To define a comprehensive model of the competencies required for the job role of GP. METHOD: Three independent studies were conducted to define GP competencies including (1) critical incidents focus groups with GPs, (2) behavioural coding of GP-patient consultations, and (3) critical incidents interviews with patients. Study 1 was conducted with GPs (n = 35) from the Trent region. Study 2 involved observation of GP-patient consultations (n = 33 consultations), and Study 3 was conducted with patients (n = 21), all from a Midlands-based medical practice. RESULTS: The data collected from the three studies provided strong evidence for a competency model comprising 11 categories with a summary of the associated behavioural descriptions. Example competencies included empathy and sensitivity, communication skills, clinical knowledge and expertise, conceptual thinking, and coping with pressure. CONCLUSIONS: Triangulation of results was achieved from three independent studies. The competencies derived imply that a greater account of personal attributes needs to be considered in recruitment and training, rather than focusing on academic and clinical competency alone. The model could be employed for future research in design of selection techniques for the role of GP.

Clinical Competence↗
PubMed1994

Aspirin reduces the incidence of colonic carcinoma in the dimethylhydrazine rat animal model.

BACKGROUND: Epidemiological studies in humans suggest that regular use of non-steroidal anti-inflammatory drugs (NSAIDS) especially aspirin significantly decreases the risk of developing colorectal cancer. AIMS: The purpose of this study was to investigate the effect of aspirin on colonic carcinogenesis using the dimethylhydrazine (DMH) colonic cancer model in rats. METHODS: Groups of animals were given daily doses of aspirin either 0, 5, 30 or 60 mg/kg for 18 weeks. Half of each group also received 18 x 30 mg/kg/wk injections of DMH. RESULTS: Aspirin at doses of 5, 30 or 60 mg/kg/dy had a progressive effect on the reduction of tumour numbers and the percentage of tumours greater or equal to 5 mm in diameter. Aspirin at doses of 30 and 60 mg/kg/dy significantly reduced tumour incidence. CONCLUSION: These findings support the epidemiological studies in humans. The rat DMH model would appear to be suitable for investigating the mechanism of action of aspirin in reducing colonic tumour formation.

Animals↗
PubMed1992

The effect of therapeutic drugs used in inflammatory bowel disease on the incidence and growth of colonic cancer in the dimethylhydrazine rat model.

An increased incidence of colonic cancer is associated with chronic inflammatory bowel disease. Sulphasalazine, metronidazole and more recently, modified forms of 5-aminosalicylic acid are used for maintenance therapy of inflammatory bowel disease. In a series of experiments, we used the 1,2-dimethylhydrazine animal model of colonic cancer in conjunction with these drugs, to study the effect on the development of colon cancer. Inbred male Wistar rats were divided into groups receiving orally: metronidazole 18 mg Kg-1 dy-1; sulphasalazine 60 mg Kg-1 dy-1; 5-aminosalicylic acid 30 and 60 mg Kg-1 dy-1 and olsalazine 60 mg Kg-1 dy-1 administered daily. Half of each group also received weekly injections of DMH 40 mg Kg-1. Metronidazole, sulphasalazine and 30 mg Kg-1 dy-1 5-aminosalicylic acid were co-carcinogenic, increasing either the number of cancers or tumour size. In contrast 60 mg Kg-1 dy-1 5-aminosalicylic acid inhibited tumour size and olsalazine had no effect. These results may have a bearing on long term maintenance therapy in inflammatory bowel disease.

Adenocarcinoma↗
PubMed1987

Evidence of hepatitis virus infection among Australian prisoners of war during World War II.

A sample of Australian male veterans of World War II was surveyed after 40 years. One hundred and seventy veterans had been held by the Japanese as prisoners of war and 172 veterans had served in southeast Asia but had not been taken captive (non-prisoners of war). A medical history was obtained and a physical examination undertaken. Blood was drawn and analysed for standard liver biochemistry and serological markers of hepatitis A and B virus (HAV, HBV) infections. The prevalence of immunoglobulin (Ig)G class antibodies to HAV was 95.2% in non-prisoners of war and 93.3% in prisoners of war. Only three cases of hepatitis B surface antigen (HBsAg) seropositivity were identified (two cases from the prisoner-of-war group). Thirty-six (21.8%) prisoners of war were seropositive for the presence of antibodies to HBsAg (anti-HBs) and 34 (20.0%) prisoners of war for that of antibodies to hepatitis B core antigen (anti-HBc), compared with 16 (9.8%) and eight (4.7%) of the non-prisoners of war, respectively (P = 0.002 and P = 0.0001, respectively). Those veterans who reported jaundice during World War II had a higher prevalence of antibodies to HBV. Among prisoners of war who were forced to work on the Burma-Thailand railway, 24.1% were seropositive for anti-HBc compared with 11.1% of the remaining prisoners of war (P = 0.048). It would appear that hepatitis B was common in prisoners of war but that those who survived 40 years were able to clear the virus and do not appear to have significant liver disease.

Asia, Southeastern↗
PubMedDate not supplied

A histological study of the use of agar as a delivery vehicle for alcohol or iron to rats.

The supply of ethanol and other substances to the rat has necessitated the development of quite complex dietary preparation and feeding techniques. This study reports the use of ethanol/water solutions in conjunction with normal rat chow diet to provide up to 30 g/kg/day ethanol to study animals. By additionally supplying agar gels containing ethanol, voluntary intake of ethanol was raised to a possible maximum of 48 g/kg/day. Hepatic steatosis was produced in 7/18 rats supplied ethanol in this fashion. Agar gels were also used to provide carbonyl iron to rats and it produced grade 3 to 4 hepatocyte iron loading in all study animals. The study demonstrates a practical method for administering ethanol and iron to rats without altering normal dietary intake. Ethanol supplied in this way does produce hepatic injury in the rat.

Agar↗
PubMedDate not supplied

Carbohydrate-deficient transferrin in the ethanol-consuming rat model.

Regular ethanol consumption leads to the appearance of carbohydrate-deficient transferrin in the plasma of human subjects. The mechanism for this finding remains uncertain. We have exposed female Wistar rats to ethanol from 3 weeks of age to 22 weeks and have studied transferrin in these animals. Isoelectric focusing (IEF) of serum identified two additional transferrin forms in the ethanol-exposed rats. Routine staining and immunofixation demonstrated transferrin focused at pH 5.45 and 5.65. Neuraminidase-treated normal rat serum focused in 2 bands at pH 5.85 and 6.15 corresponding to the additional bands in ethanol-treated rats. Human transferrin exposed to neuraminidase focused at pH 5.7 as described by others. The results suggest that the rat may be used as an animal model to study the complex effects of ethanol on transferrin and iron metabolism.

Alcohol Drinking↗
PubMedDate not supplied

Interaction between variation in the D2 dopamine receptor (DRD2) and the neuronal calcium sensor-1 (FREQ) genes in predicting response to nicotine replacement therapy for tobacco dependence.

We have previously demonstrated that a functional dopamine D2 receptor promoter variant (DRD2 -141 Ins/Del) predicts response to nicotine replacement therapy (NRT). The present study extends this finding in the same population of 363 NRT-treated subjects, by examining variation in the gene encoding the neuronal calcium sensor-1 protein (FREQ), which functions to regulate D2 receptor desensitization. The results indicate a statistically significant interaction effect of DRD2-141 and FREQ genotypes on abstinence at the end of the NRT treatment phase; 62% of the smokers with at least one copy of the DRD2 -141 Del allele and two copies of the FREQ rs1054879 A allele were abstinent from smoking, compared to 29-38% abstinence rates for other smokers in the trial. This result suggests that the interaction between variation in the DRD2 and FREQ genes, which both encode components of the D2 dopamine receptor signal transduction pathway, impacts the efficacy of NRT.

Administration, Cutaneous↗
PubMedDate not supplied

Changing prevalence of hepatitis B virus in urbanized Australian aborigines.

Serological surveys of desert or rural Australian Aboriginal settlements report up to 85% positivity for hepatitis B virus (HBV) markers. We report the results of two cross-sectional HBV surveys carried out 5 years apart in the bi-racial town of Condobolin, New South Wales (population 3086; 14% Aborigines). In 1983-84, none of the 310 non-Aborigines tested were hepatitis B surface antigen (HBsAg) positive but 7.2% were positive for hepatitis B core antibody (anti-HBc). Among Aboriginal subjects, 57.6% had detectable HBV markers and 16.9% were HBsAg positive. In 1987-88, no non-Aborigines were HBsAg positive and only 1% (of 422 individuals) had anti-core antibodies. In contrast, 36% of Aboriginal subjects had HBV markers and 6% were HBsAg positive. No significant difference in detectable HBV markers was found among 98 Aborigines who were included in both surveys. Migration was the main factor influencing the HBV prevalence between the two surveys. Clustering of HBsAg carriers occurred within households and the likely mode of infection was intrafamilial horizontal childhood transmission. There was a significant association between HBV markers and tattooing in Aborigines (P < 0.02). Overall, HBV markers were less frequent in this population than in other desert or rural Aboriginal populations surveyed. The prevalence of HBV infection in non-Aboriginal households was not significantly different from that in the Australian Caucasian population.

Adult↗