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Biomedical subjects

John Crowe

Publications and source records attributed to John Crowe.

9 recordsLinked to original sources
PubMed2006

Hepatic iron metabolism gene expression profiles in HFE associated hereditary hemochromatosis.

BACKGROUND: Individuals with pathogenic mutations in HFE, hemojuvelin (HJV) and transferrin receptor 2 (TfR2) have low levels of hepcidin, but little is known about the hepatic expression of these molecules in patients with physiological iron overload or HFE associated Hemochromatosis (HH). AIMS: To examine the hepatic mRNA expression of iron homeostasis genes in patients with HH, physiological iron overload and healthy controls. PATIENTS: Untreated C282Y homozygous HH patients (n=20) with elevated serum ferritin (SF) and patients with physiological iron overload (n=12) with positive hepatocellular iron staining and negative HFE mutation analysis were evaluated. The control cohort (n=10) had normal iron parameters, negative HFE mutation analysis and negative hepatocellular iron staining. METHODS: Hepcidin, HJV (hemojuvelin), TfR2 (transferrin receptor 2), HFE, IL6 (interleukin 6) and ferroportin mRNA expression patterns were evaluated using quantitative real-time PCR. RESULTS: Physiological iron overload led to significantly upregulated hepcidin, HJV and ferroportin mRNA expression while TfR2 expression was not significantly different to controls. In contrast, HFE associated iron overload failed to induce hepcidin or HJV. TfR2 mRNA expression was significantly reduced when compared to controls. Ferroportin expression in HH was comparable to that found in physiological iron overload. Neither HFE nor IL6 expression was altered by variation in iron status. CONCLUSIONS: These findings suggest that patients with HH, in contrast to those with physiological iron overload, have a weakened TfR2 sensing mechanism that leads to the lack of induction of hepcidin and HJV. The C282Y HFE mutation does not appear to impede the hepatocellular iron export function of ferroportin.

Adult↗
PubMed2006

Assessment of fibrosis progression in untreated irish women with chronic hepatitis C contracted from immunoglobulin anti-D.

BACKGROUND & AIMS: In 1996 we initiated a retrospective-prospective study in 184 untreated women infected in 1977 with chronic hepatitis C virus (HCV). To provide insight into the natural history of HCV, we determined liver fibrosis outcomes and any predictors of such. METHODS: Baseline 1994 biopsy specimens (size, >or=15 mm; portal areas, >or=5) and sequential biopsy specimens were assessed by Ishak score for grade change (increase or decrease of >or=2 points) and stage progression or regression (increase or reduction of >or=1 point), the latter correlated with digital quantification of fibrosis percentage. RESULTS: No baseline biopsy specimens had cirrhosis, therefore all could potentially progress. Grade and stage scores decreased or increased significantly in 28% and 18% and 24% and 27% of patients, respectively. There was a positive correlation between baseline and sequential grade/stage scores (r = .39, P < .001), and between semiquantitative Ishak scores and fibrosis percentage (Spearman rho = .85; P < .01). Baseline alanine transaminase values (mean, 49 U/L; range, 23-363 U/L) correlated positively with changes in grade (r = .41, P < .01) and stage (r = .39, P < .01), and regression analyses indicated that baseline alanine transaminase value was a good predictor of such changes. Confounding variables (alcohol, smoking, and herbal and paracetamol [acetaminophen] use) did not correlate with histologic outcomes. CONCLUSIONS: In a follow-up study, 49% of patients showed no change in fibrosis, 24% showed regression, and only 27% showed progression, including 4 patients (2.1%) who developed stage 6 cirrhosis. Unidirectional sequential grade/stage concordance attested to biopsy sample reliability. Given the current age of these women in their fifth decade, some still may have a risk for more advanced liver disease, but for most of these patients it appears unlikely.

Adult↗
PubMed2005

Host immune responses in hepatitis C virus clearance.

BACKGROUND AND AIM: The factors that determine the outcome of hepatitis C virus (HCV) infection are not fully understood. An increased and broadly targeted/multispecific T-cell response is thought to be paramount to a favourable outcome. Human leucocyte antigen (HLA) genes, in particular DRB1 and DQB1, are also reported to influence outcome of infection. We have previously demonstrated strong associations between DRB10101 and spontaneous viral clearance. The aim of the current study was to investigate HCV-specific T-cell response and the influence of DRB10101 in patients with long-term history of HCV clearance as compared to patients that developed persistent HCV infection. METHODS: The proliferation of peripheral blood mononuclear cells stimulated with five non-structural and core HCV antigens and 20 synthesized HCV peptides, designed using T-cell epitope-predictive software, was determined by the incorporation of H-thymidine. RESULTS: Although HCV-specific T-cell responses were more frequently detected and a broader range of peptides were targeted in the viral clearance group, the magnitude and breadth of the responses were not significantly different to that in the viral persistence group. The magnitude and breadth of the T-cell response was significantly associated, however, with possession of DRB10101. Furthermore DRB10101 positive individuals with viral clearance had broader HCV-specific T-cell responses. CONCLUSION: These findings lend further credence to the importance of the host immune system to the outcome of HCV infection and provide a rationale for the role of DRB10101 in the resolution of HCV infection.

Cells, Cultured↗
PubMed2004

Evaluation of a model of adjustment to an iatrogenic hepatitis C virus infection.

OBJECTIVE: The aim of this study was to evaluate a model of adjustment to an iatrogenic hepatitis C(HCV) infection in a cohort of women. PARTICIPANTS: Eighty-three women diagnosed with an iatrogenic HCV infection were recruited; 49 women had chronic infection (PCR positive) and the remaining 34 women were considered to have a self-limiting HCV infection (PCR negative). MEASURES: The Hepatitis C Survey Questionnaire (HCSQ; Coughlan, Sheehan, Carr, & Crowe, unpublished) and the General Health Questionnaire (GHQ30; Goldberg & Williams, 1988) were used in this study. RESULTS: Structural equation modelling (SEM) was carried out to evaluate and modify a recursive path model using Moos and Schaefer's (1984) model of coping with illness as the basis for developing a multivariate model of adjustment to an iatrogenic HCV infection. The final model fit, chi(2)(30) = 21.9 p =.86, CFI = 1.00, RMSEA = 0.000, was judged to be theoretically acceptable, indicating that positive illness appraisal, ability to work and negative behaviour as a consequence of feelings of anger and blame are directly related to adjustment. CONCLUSION: This model has provided support for the following general relationships, namely that, adjustment to an iatrogenic HCV infection is related to: (1) illness and social factors; (2) cognitive appraisals; (3) adaptive tasks; and (4) coping skills thus emphasizing the need to develop a biopsychosocial model of treatment.

Adaptation, Psychological↗
PubMed2002

Menstrual symptometrics: a simple computer-aided method to quantify menstrual cycle disorders.

OBJECTIVE: To validate a menstrual symptometrics device that can quantify menstrual blood loss, dysmenorrhea, and the premenstrual syndrome against traditional methods of collecting data on symptoms. DESIGN: Validation study. SETTING: Academic research clinic for menstrual cycle disorders. PARTICIPANT(S): Women 18-50 years of age who presented with menstrual cycle disorders. Controls were recruited from lists of patients requesting sterilization and from hospital staff. INTERVENTION(S): Participants were asked to complete the menstrual symptometrics device and to record pain, blood loss, and premenstrual symptoms by using traditional methods (paper-based scales and the alkaline hematin method) for two cycles. MAIN OUTCOME MEASURE(S): Agreement between traditional methods of quantifying menstrual cycle disorders and data obtained from the menstrual symptometrics device, and acceptability of the latter technique to patients. RESULT(S): A high level of agreement was observed between the traditional methods and the menstrual symptometrics device in quantifying and diagnosing menorrhagia, dysmenorrhea, and the premenstrual syndrome. Most patients preferred the menstrual symptometrics device as a data collection tool. CONCLUSION(S): The menstrual symptometrics device is a rapid and accurate method of quantifying blood loss, pain, and premenstrual symptoms. It has a high level of patient acceptability and can provide instant pictorial feedback on symptoms for patients and clinicians.

Adult↗
PubMed2002

Psychological well-being and quality of life in women with an iatrogenic hepatitis C virus infection.

OBJECTIVE: This study documents psychological well-being, mental health and quality of life in a group of women diagnosed with an iatrogenic hepatitis C (HCV) infection and examines the relationship between HCV RNA status and adjustment to their illness. DESIGN: A cross-sectional design was used. METHOD: Psychological well-being, mental health and quality of life were assessed in a consecutive clinical sample of 93 women who were anti-HCV positive (ELISA, third generation). Of these, 33 had a self-limiting HCV infection (HCV RNA negative), whereas 60 had chronic HCV infection (HCV RNA positive). RESULTS: Overall, psychological well-being and mental health were diminished in all women and were best predicted by their level of social functioning, which accounted for between 42% and 57% of the variance. When comparing women with chronic HCV infection and those with a self-limiting HCV infection, no differences were detected in quality of life and no association was found between HCV RNA status and a clinical diagnosis of depression or anxiety. Furthermore, no significant differences were demonstrated in HCV RNA positive women when compared according to liver histology on all measures. CONCLUSION: In both HCV RNA positive and HCV RNA negative women, high levels of psychological distress and impaired quality of life were found. Impairments were not related to HCV RNA status or liver histology.

Journal Article↗
PubMed2002

Hereditary hemochromatosis: a common, often unrecognized, genetic disease.

Hereditary hemochromatosis in people of northern European descent is more common than many physicians realize. It causes excessive gastrointestinal absorption of iron, leading to potentially fatal iron deposition in multiple organs. Early diagnosis and phlebotomy to reduce iron stores can prevent complications and provide normal life expectancy. Genetic testing of relatives of patients with hemochromatosis is warranted in some circumstances.

Algorithms↗
PubMedDate not supplied

DMT1 genetic variability is not responsible for phenotype variability in hereditary hemochromatosis.

BACKGROUND/AIMS: Homozygosity for a cysteine to tyrosine translocation at position 282 within the HFE gene (C282Y) is responsible for over 90% of hereditary hemochromatosis (HH) in Celtic populations. Determining those C282Y homozygotes at greatest risk for iron overload is a major clinical concern as only a small percentage will develop clinically significant iron overload. Divalent metal transport protein (DMT1) on the apical surface of duodenal enterocytes is recognised as the major iron import protein. We investigated whether genetic variability within the DMT1 gene may partly explain the phenotypic variability seen amongst a group of C282Y homozygotes with iron overload. METHODS: One hundred and one unrelated C282Y homozygotes and 103 C282Y negative controls were analysed for the presence of four specific mutations/polymorphisms within the DMT1 gene (1245T/C, 1303C/A, IVS4 + 44C/A, IVS15Ex16-16C/G) using standard PCR techniques. Hepatic iron deposition was determined in 32 HH patients following Perls Prussian blue staining (0-4+). Estimations of the haplotype frequencies were performed utilising the program Arlequin version 2. RESULTS: There were no significant differences in the allele frequencies of the IVS4 + 44C/A, 1303C/A, 1254T/C and IVS15Ex16-16C/G polymorphisms in the patient cohort compared to those observed in the control cohort. The commonest haplotypes identified were CCTC: IVS4C + 44C, 1303C, 1254T, IVS15ex16-16C; ACCC: IVS4C + 44A, 1303C, 1254C, IVS15ex16-16C and ACTG: IVS4C + 44A, 1303C, 1254T, IVS15ex16-16G. Similarly, there were no significant differences in the frequencies of these three haplotypes in the patient cohorts (regardless of the degree of hepatic iron deposition) compared to the control cohort. CONCLUSIONS: Polymorphisms within DMT1 gene do not influence penetrance of the HH phenotype.

Adolescent↗