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David M Purdie

Publications and source records attributed to David M Purdie.

80 records · Page 5Linked to original sources
PubMed2002

Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis.

BACKGROUND & AIMS: The progression of fibrosis to cirrhosis is the most significant prognostic factor in hereditary hemochromatosis. We aimed to determine the range of hepatic iron concentration associated with cirrhosis in the absence of alcohol and other pro-fibrogenic cofactors and to quantify the contribution of excess alcohol consumption to the development of cirrhosis. METHODS: Liver biopsy data were evaluated on 224 C282Y homozygous hemochromatosis subjects. To determine the effect of alcohol alone on the development of fibrosis, subjects with viral hepatitis or nonalcoholic steatohepatitis were excluded. Subjects were divided into those who consumed less than 60 g alcohol per day and those who consumed 60 g per day or more. RESULTS: Seven percent of subjects who consumed less than 60 g per day had severe fibrosis/cirrhosis compared with 61% of excess alcohol consumers. CONCLUSIONS: Hemochromatosis subjects who drink more than 60 g alcohol per day are approximately 9 times more likely to develop cirrhosis than those who drink less than this amount, and the range of hepatic iron concentration associated with cirrhosis in the absence of cofactors was 233-675 micromol/g dry weight.

Adult↗
PubMed2002

The CYP3A4*1B polymorphism has no functional significance and is not associated with risk of breast or ovarian cancer.

CYP3A4 is involved in the metabolism of endogenous steroids, and an allelic variant, CYP3A4*1B, consisting of an A to G polymorphism within the 5'-flanking region termed the nifedipine-specific response element (NFSE) has been associated with high grade and advanced stage of prostate cancers. Because steroid hormone exposure is known to influence breast and ovarian cancer risk, we conducted case-control studies to assess the relationship between CYP3A4*1B and risk of breast or ovarian cancer. CYP3A4 NFSE genotype was determined in 951 breast cancer cases and 500 controls frequency matched for age and 488 ovarian cancer cases and 276 controls of similar age distribution. Case-control analyses and comparisons of genotype distributions were conducted by unconditional logistic regression. In addition, the functional significance of the CYP3A4*1B polymorphism was assessed by analysis of CYP3A4-reporter gene constructs transiently transfected into liver-derived cell lines and primary cultures of well-differentiated rat hepatocytes. The GG genotype was rare in all groups (0-0.4%). There was no risk of cancer associated with the AG/GG genotypes combined, with an OR (95% CI) of 0.86 (0.54-1.33) for breast cancer (P = 0.5), and 1.51 (0.80-2.89) for ovarian cancer (P = 0.2). Analysis of CYP3A4-luciferase constructs showed that CYP3A4*1B did not consistently affect reporter gene activity. Our data suggest that the CYP3A4*1B polymorphism is not associated with risk of breast or ovarian cancer. In support of this negative finding, in-vitro functional studies indicate that NFSE genotype is not a critical factor in the transcriptional activity of the CYP3A4 5'-flanking region, and is thus unlikely to modulate CYP3A4-mediated metabolism of steroids.

5' Untranslated Regions↗
PubMed2002

The risk of Ross River and Barmah Forest virus disease in Queensland: implications for New Zealand.

OBJECTIVES: To describe the incidence of Ross River (RR) and Barmah Forest (BF) virus disease in Queensland and determine the risk of importation of RR virus from Queensland into New Zealand (NZ) via viraemic travellers. METHODS: Based on routine RR and BF virus notification data of seven major urban tropical and subtropical Queensland populations, incidence rates adjusted for age, sex, season and a baseline level of immunity were used to examine the annual and seasonal risk of disease in the specific populations and selected subgroups. The risk for NZ was determined by estimating the number of infections among major visitor groups travelling from Queensland to NZ, using seroconversion rates. RESULTS: In Queensland, annual rates of RR and BF virus disease ranged between 31.5-288.3 and 3.4-37.4/100,000 person years respectively and increased to between 48.4-423.5 and 3.8-40.4/100,000 person years at risk when adjusted for immunity. Our estimates indicate that more than 100 viraemic travellers may enter NZ from Queensland each year. Estimates were greatest among New Zealanders returning home. CONCLUSIONS AND IMPLICATIONS: Usefulness of notification data could be maximised by presenting more detailed information to the local governments responsible for the control and public health awareness of these pathogens. Given the high number of viraemic persons entering NZ, the abundance of possums and the emergence of Oc. camptorhynchus, transmission of RR virus within NZ is probable. Health authorities should prepare for a virgin soil epidemic of RR virus by initiating serological and clinical surveillance in key areas, enhance public and professional awareness and elevate national resources necessary to invoke emergency vector control and case management.

Adolescent↗
PubMedDate not supplied

Association between apolipoprotein E epsilon4 and neuropsychiatric symptoms during interferon alpha treatment for chronic hepatitis C.

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Adult↗
PubMedDate not supplied

Visual-tactile examination compared with conventional radiography, digital radiography, and Diagnodent in the diagnosis of occlusal occult caries in extracted premolars.

PURPOSE: This laboratory study compared visual-tactile examination with conventional radiographs, digital radiographs, and laser fluorescence in the detection of occlusal occult caries on extracted premolar teeth. METHODS: Extracted premolars without obvious caries or restorations were collected from school dental clinics. Occlusal surfaces of 320 extracted premolars were examined visually with an explorer, then examined using the KaVo Diagnodent unit and scored using specific criteria. The teeth were exposed using conventional and digital radiography, respectively. The radiographs were assessed for dentin radiolucencies beneath the occlusal surface. RESULTS: Of the 320 teeth used in this study, 302 were scored as sound by visual-tactile examination. Of these, 57 (19%) demonstrated dentin radiolucency on conventional bite-wings, and 245 (81%) were scored as radiographically sound. Thus, the sensitivity and specificity values of the visual-tactile examination compared with conventional radiography were 81% and 44%, respectively. In contrast, Diagnodent produced results of 82% sensitivity and 36% specificity when compared with conventional radiography. When compared to digital radiography, the sensitivity and specificity values of the visual-tactile examination were 90% and 44%, respectively. In contrast, when compared to digital radiography, Diagnodent showed a very low specificity of only 32%, although sensitivity was still high at 91%. Differences in specificity among the techniques were statistically significant (P < .03), whereas differences in sensitivity were not (P > .01). CONCLUSIONS: Although the diagnosis of occult dentinal caries may be further enhanced by the Diagnodent, a combination of visual-tactile examination and either conventional or digital radiography should identify over 80% of lesions.

Adolescent↗
PubMedDate not supplied

Searching for cancer deaths in Australia: National Death Index vs. cancer registries.

OBJECTIVE: To compare the accuracy, costs and utility of using the National Death Index (NDI) and state-based cancer registries in determining the mortality status of a cohort of women diagnosed with ovarian cancer in the early 1990s. METHODS: As part of a large prognostic study, identifying information on 822 women diagnosed with ovarian cancer between 1990 and 1993, was simultaneously submitted to the NDI and three state-based cancer registries to identify deceased women as of June 30, 1999. This was compared to the gold standard of "definite deaths". A comparative evaluation was also made of the time and costs associated with the two methods. RESULTS: Of the 450 definite deaths in our cohort the NDI correctly identified 417 and all of the 372 women known to be alive (sensitivity 93%, specificity 100%). Inconsistencies in identifiers recorded in our cohort files, particularly names, were responsible for the majority of known deaths not matching with the NDI, and if eliminated would increase the sensitivity to 98%. The cancer registries correctly identified 431 of the 450 definite deaths (sensitivity 96%). The costs associated with the NDI search were the same as the cancer registry searches, but the cancer registries took two months longer to conduct the searches. CONCLUSIONS AND IMPLICATIONS: This study indicates that the cancer registries are valuable, cost effective agencies for follow-up of mortality outcome in cancer cohorts, particularly where cohort members were residents of those states. For following large national cohorts the NDI provides additional information and flexibility when searching for deaths in Australia. This study also shows that women can be followed up for mortality with a high degree of accuracy using either service. Because each service makes a valuable contribution to the identification of deceased cancer subjects, both should be considered for optimal mortality follow-up in studies of cancer patients.

Adult↗
PubMedDate not supplied

Repeatability of self-reported information for population-based studies of cancer.

PURPOSE: To measure the repeatability of a cancer risk factor questionnaire in a population-based case-control study. METHODS: Questionnaires were completed on two occasions by patients with cancer of the ovary (n=25) or esophagus (n=23) and by 37 controls without cancer. We assessed general cancer risk factors including height and weight (for calculating body mass index (BMI)), smoking and anti-inflammatory (NSAID) use. Risk factors specific for ovarian and esophageal cancers were also assessed. Agreement was measured by the correlation coefficient and weighted kappa statistic (kw) for continuous and categorical variables respectively. RESULTS: We observed very high levels of agreement for BMI (kw=0.84) and smoking history, including ages at initiation and quitting (Pearson correlation = 0.87 and 0.86 respectively). There was moderate to substantial agreement for use of anti-inflammatory drugs (aspirin kw =0.52, other NSAIDS kw =0.72). Agreement for lifetime prevalence of medical conditions varied from almost perfect (e.g. history of benign breast disease (k =0.86)) to moderate (e.g. heartburn (k =0.57)). Item repeatability was not materially altered by case-control status, age or sex of respondents or interval between completions. CONCLUSIONS: Self-reported cancer risk factor information demonstrates moderate to almost perfect levels of agreement, suggesting these items are suitable for risk estimation and epidemiologic inference.

Adult↗