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Biomedical subjects

B Coughlan

Publications and source records attributed to B Coughlan.

14 recordsLinked to original sources
PubMed2003

An investigation of the psychosocial impact of a Compensation Tribunal on women with latrogenic hepatitis C infection.

The aim of this study was to investigate the psychosocial impact of a Compensation Tribunal in women with an iatrogenic hepatitis C virus (HCV) infection. Eighty-three women diagnosed with an iatrogenic HCV infection were recruited, 19 women were Pre-Tribunal and 64 women were post-Tribunal. Both standardised and disease specific psychological measures were used. A series of t-tests revealed no differences in psychological well-being and adjustment to HCV infection in women pre and post Compensation Tribunal. Chi-square tests revealed no association between PCR status and 1) psychological well-being and 2) experience of anger/blame in women post-Compensation Tribunal. A further series of t-tests revealed that women with high levels of anger and blame post-Compensation Tribunal perceived their future as more uncertain, experienced more pain, low self-esteem and psychological distress, viewed their ability to work as impeded and complained of increased stress preparing for their Compensation Tribunal. This study suggests that poor adjustment in women with an iatrogenic HCV infection post-Compensation Tribunal is not associated with attendance at a Compensation Tribunal nor PCR status but rather to experiences of anger and blame.

Adaptation, Psychological↗
PubMed2002

Underdiagnosis of hereditary haemochromatosis: lack of presentation or penetration?

BACKGROUND: The majority of hereditary haemochromatosis (HH) patients are homozygous for the C282Y mutation in the HFE gene. We have demonstrated a homozygote frequency of 1 in 83 for the C282Y mutation in a retrospective analysis of Irish neonates. However, a fully developed phenotype is not observed at the same frequency clinically, suggesting that a large proportion of Irish HH patients may remain undiagnosed. AIMS: To determine whether underdiagnosis of HH results from the non-specific nature of early symptoms or incomplete penetrance of the C282Y mutation. METHODS: Seventy nine C282Y homozygous individuals identified from family screening for HH and 30 HH probands were investigated. Non-specific symptoms (fatigue, arthropathy, and impotence) and their association with iron indices (transferrin saturation and serum ferritin) and hepatic iron deposition were analysed. RESULTS: We found that 78% of men (mean age 42 years) and 36% of women (mean age 39 years) who were identified as C282Y homozygotes following family screening had iron overload, as defined by a transferrin saturation >or=52% combined with a serum ferritin >or=300 microg/l for men and >or=200 microg/l for women. The frequency of reports of non-specific symptoms in those individuals with iron overload was not significantly different from those who did not have iron overload. CONCLUSIONS: Our findings indicate that underdiagnosis of HH may be due to the non-specific nature of early symptoms and less frequently to the incomplete penetrance of the C282Y mutation.

Adult↗
PubMed2001

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection.

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.

Alanine Transaminase↗
PubMed1999

Objective evaluation of regional left ventricular wall motion during dobutamine stress echocardiographic studies using segmental analysis of color kinesis images.

OBJECTIVES: To test the feasibility of objective and automated evaluation of echocardiographic stress tests, we studied the ability of segmental analysis of color kinesis (CK) images to detect dobutamine-induced wall motion abnormalities and compared this technique with inexperienced reviewers of conventional gray-scale images. BACKGROUND: Conventional interpretation of stress echocardiographic studies is subjective and experience dependent. METHODS: CK images were obtained in 89 of 104 consecutive patients undergoing clinical dobutamine stress studies and were analyzed using custom software to calculate regional fractional area change in 22 segments in four standard views. Each patient's data obtained at rest was used as a control for automated detection of dobutamine-induced wall motion abnormalities. Independently, studies were reviewed without CK overlays by two inexperienced readers who classified each segment's response to dobutamine. A consensus reading of two experienced reviewers was used as the gold standard for comparisons. In a subgroup of 16 patients, these consensus readings and CK detection of wall motion abnormalities were compared with coronary angiography. RESULTS: The consensus reading detected ischemic response to dobutamine in 43 of 1958 segments in 23 of 89 patients. Automated detection of stress-induced wall motion abnormalities correlated more closely with the standard technique than the inexperienced reviewers (sensitivity 0.76 vs. 0.55, specificity 0.98 vs. 0.94 and accuracy 0.97 vs. 0.92). When compared with coronary angiography in a subgroup of patients, analysis of CK images differentiated between normal and abnormal wall motion more accurately than expert readers of gray-scale images (accuracy of 0.93 vs. 0.82). CONCLUSIONS: Analysis of CK images allows fast, objective and automated evaluation of regional wall motion, sensitive enough for clinical dobutamine stress data and more accurate than inexperienced readers. This method may result in a valuable adjunct to conventional visual interpretation of dobutamine stress echocardiography.

Aged↗
PubMed1999

Left atrial appendage stenosis.

Narrowing at the mouth of the left atrial appendage has been reported after partial surgical ligation of the appendage. This report describes a patient, without prior cardiac surgery, who had an anatomic narrowing at the opening of the left atrial appendage demonstrated by 2-dimensional, Doppler, and color Doppler echocardiography.

Aged↗
PubMed1999

Fatigue does not correlate with the degree of hepatitis or the presence of autoimmune disorders in chronic hepatitis C infection.

BACKGROUND: Fatigue is probably the most commonly reported symptom in chronic hepatitis C virus (HCV) infection. It is unclear whether fatigue is related to the severity of underlying liver disease or other autoimmune disorders often described with chronic HCV infection. OBJECTIVE: To quantify fatigue in terms of its impact on quality of life in a homogeneous cohort and examine its relationship to the status of liver disease or associated autoimmunity. METHODS: The Fatigue Impact Scale (FIS) questionnaire (Fisk et al. Clin Infect Dis 1994; 18:S79-S83), a recently validated psychometric tool for assessing patients' perceptions of the functional limitations attributable to fatigue (40 statements; three subscales: physical, cognitive and psychological; maximum score = 160), was applied to a cohort of Irish women who were PCR-positive for HCV genotype 1b via inoculation with contaminated anti-D products in 1977. RIBA-positive, PCR-negative patients (n = 20) and healthy age-matched women (n = 50) served as controls. The degree of hepatitis was assessed using the Knodell histological activity index (HAI) score on previous liver biopsies. Clinical and laboratory evidence of cryoglobulinaemia, Sjogren's syndrome, connective tissue diseases, autoimmune thyroid disease and glomerulonephritis was sought. RESULTS: The mean FIS score of the 66 PCR-positive women (mean 78+/-36; range 7-153) was significantly higher than in age-matched controls (mean 31+/-24, range 0-78, P<0.001) but not statistically different from that of the RIBA-positive, PCR-negative group. The FIS score did not correlate with the HAI score (median HAI = 4; range 2-9; Pearson's correlation coefficient r=0.01, P=0.9). Significant levels of cryoglobulins were detected in 10 (15.2%). The sicca complex was diagnosed in six patients, three of whom had associated cryoglobulinaemia. Thyroid antibodies, anti-nuclear antibody, rheumatoid factor, antimitochondrial antibody and anti-smooth muscle antibody were detected in 15.2%, 6%, 4.5%, 4.5% and 1.5%, respectively. There was no significant difference in the FIS score between the groups with autoimmune diseases and those without. The FIS score of the nine patients previously treated with interferon was not statistically different from the untreated group (P=0.39). CONCLUSION: The perceived functional impact of fatigue on quality of life is significantly higher in patients with chronic HCV genotype 1b infection compared to healthy controls. However, it is unrelated to the degree of hepatitis and cannot be accounted for by the co-existence of autoimmune disorders alone.

Adult↗
PubMed1995

p53 expression and DNA ploidy of cartilage lesions.

The aim of this study was to investigate the expression of a tumor suppressor gene (p53) in cartilage lesions of bone and its relationship to their histological grade and DNA ploidy. An immunohistochemical assay for p53 and Feulgen-stained DNA preparations was subjected to computerized image analysis. Enchondromas, synovial chondromatosis, and low grade (grade I and II) chondrosarcomas were diploid. High grade (grade III) chondrosarcomas and high grade sarcomatous components of dedifferentiated chondrosarcomas were aneuploid. Well differentiated cartilaginous components of dedifferentiated chondrosarcomas were diploid. Microscopic examination showed weak focal positivity for p53 in one of 10 enchondromas one of six examples of synovial chondromatosis, and three of four low grade (grade I and II) chondrosarcomas. All three high grade (grade III) chondrosarcomas were strongly positive for p53. The high grade sarcomatous component of all four dedifferentiated chondrosarcomas was strongly positive for p53, whereas only focal weak positivity was noted in the well differentiated cartilaginous areas. These results were confirmed by quantitative computer-assisted image analysis, which showed that high grade aneuploid cartilage tumors demonstrated strikingly higher levels of p53 than did diploid low grade malignant tumors or benign cartilage lesions.

Adult↗
PubMedDate not supplied

Increased duodenal DMT-1 expression and unchanged HFE mRNA levels in HFE-associated hereditary hemochromatosis and iron deficiency.

HFE-associated hereditary hemochromatosis is characterized by imbalances of iron homeostasis and alterations in intestinal iron absorption. The identification of the HFE gene and the apical iron transporter divalent metal transporter-1, DMT-1, provide a direct method to address the mechanisms of iron overload in this disease. The aim of this study was to evaluate the regulation of duodenal HFE and DMT-1 gene expression in HFE-associated hereditary hemochromatosis. Small bowel biopsies and serum iron indices were obtained from a total of 33 patients. The study population comprised 13 patients with hereditary hemochromatosis (C282Y homozygous), 10 patients with iron deficiency anemia, and 10 apparently healthy controls, all of whom were genotyped for the two common mutations in the HFE gene (C282Y and H63D). Total RNA was isolated from tissue and amplified via RT-PCR for HFE, DMT-1, and the internal control GAPDH. DMT-1 protein expression was additionally assessed by immunohistochemistry. Levels of HFE mRNA did not differ significantly between patient groups (P = 0.09), specifically between C282Y homozygotes and iron deficiency anemic patients, when compared to controls (P = 0.09, P = 0.9, respectively). In contrast, DMT-1 mRNA levels were at least twofold greater in patients with hereditary hemochromatosis and iron deficiency anemia when compared to controls (P = 0.02, P = 0.01, respectively). Heightened DMT-1 protein expression correlated with mRNA levels in all patients. Loss of HFE function in hereditary hemochromatosis is not derived from inhibition of its gene expression. DMT-1 expression in C282Y homozygote subjects is consistent with the hypothesis of a "paradoxical" duodenal iron deficiency in hereditary hemochromatosis. The observed twofold upregulation of the DMT-1 is consistent with the slow but steady increase in body iron stores observed in those presenting with clinical features of hereditary hemochromatosis.

Cation Transport Proteins↗
PubMedDate not supplied

Hepatitis C among drug users: consensus guidelines on management in general practice.

BACKGROUND: Hepatitis C (HCV) is a common cause of morbidity among patients who attend general practitioners (GPs) in Ireland for methadone maintenance treatment. AIMS: To describe the development and content of guidelines for the management of HCV among current or former opiate users in the Eastern Regional Health Authority area attending GPs for methadone treatment. METHODS: The guidelines were produced in five stages: identification of key stakeholders; development of evidence-based draft guidelines; discussion of content; determination of 'Delphi'-facilitated consensus and review by a sample of GPs for whom the guidelines would be intended. RESULTS: The guidelines contain advice for GPs on all aspects of care of patients at risk of HCV, including general and preventative care, care of other bloodborne and hepatotoxic viruses, and the factors to be considered and appropriate evaluation prior to referring a patient for assessment at a hepatology unit. CONCLUSIONS: GPs have an important role to play in the care of patients at risk of, or infected with, HCV.

Adolescent↗