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51.
MB Delatycki M Wolthuizen MA Aitken C Hickerton SA Metcalfe KJ Allen 《Clinical genetics》2013,84(3):286-289
Hereditary hemochromatosis (HH) is a common preventable disorder of iron overload that can result in liver cirrhosis and reduced lifespan. Most HH is due to homozygosity for the HFE p.C282Y substitution. We conducted a study of screening for p.C282Y in high schools where p.C282Y heterozygotes (CY) individuals were informed of their genotype by letter. We studied whether these individuals understood the implications of their genotype, whether this resulted in anxiety or reduced health perception and whether cascade testing was higher in families of CY than wild‐type homozygous (CC) individuals. We found 586 of 5757 (1 in 10) screened individuals were CY. One month after receiving their result, 83% correctly answered that they have one copy of p.C282Y. There was no adverse change in anxiety or health perception from prior to screening to 1 month after receiving results. Significantly more family members of CY individuals than CC individuals were informed about HH and had testing for HH. In conclusion, we found that informing CY individuals of their genotype does not increase anxiety and the implications are generally well understood. This leads to cascade testing in a minority of families. CY individuals should be informed of their genetic status when identified by population screening. 相似文献
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Elevation of Carbohydrate Antigen 19.9 in Benign Hepatobiliary Conditions and Its Correlation with Serum Bilirubin Concentration 总被引:2,自引:0,他引:2
Ong SL Sachdeva A Garcea G Gravante G Metcalfe MS Lloyd DM Berry DP Dennison AR 《Digestive diseases and sciences》2008,53(12):3213-3217
Background Carbohydrate antigen 19.9 (CA19.9), a tumor marker for malignancies of the hepatobiliary tract and pancreas, has frequently
been shown to be deranged in a number of non-malignant conditions that are associated with jaundice. This study aims to demonstrate
the correlation between CA19.9 and serum bilirubin concentration in patients with benign conditions and to determine the frequency
of a false-positive increase in CA19.9 in patients being investigated for potential HPB malignancies. Methods This is a retrospective review of 83 consecutive patients presenting with an abnormal CA19.9 and radiological or clinical
features suggestive of HPB malignancy subsequently shown to have benign disease. All patients were thoroughly investigated
and followed up until the diagnosis of malignancy could be safely excluded. Results Serum bilirubin, sodium, lymphocyte count, neutrophil:lymphocyte ratio (NLR), β-human chorionic gonadotrophin (HCG), and
age were found to correlate with CA19.9 by Pearson’s correlation (P = 0.001, P = 0.006, P = 0.006, P < 0.001, P = 0.012, and P = 0.049, respectively). In multivariate regression analysis, bilirubin was identified as an independent variable that may
predict CA19.9 level (P = 0.028). Conclusion CA19.9 level is significantly influenced by serum bilirubin and elevated levels have been observed in patients with non-malignant
HPB conditions. Adjusting CA19.9 according to bilirubin levels is likely to improve the specificity of this antigen in the
differential diagnosis of benign and malignant HPB diseases and its reliability in the monitoring of disease response to chemotherapy. 相似文献
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Identification of a point mutation in the catalytic domain of the protooncogene c-kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. 总被引:27,自引:0,他引:27 下载免费PDF全文
H Nagata A S Worobec C K Oh B A Chowdhury S Tannenbaum Y Suzuki D D Metcalfe 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(23):10560-10564
Both stem cells and mast cells express c-kit and proliferate after exposure to c-kit ligand. Mutations in c-kit may enhance or interfere with the ability of c-kit receptor to initiate the intracellular pathways resulting in cell proliferation. These observations suggested to us that mastocytosis might in some patients result from mutations in c-kit. cDNA synthesized from peripheral blood mononuclear cells of patients with indolent mastocytosis, mastocytosis with an associated hematologic disorder, aggressive mastocytosis, solitary mastocytoma, and chronic myelomonocytic leukemia unassociated with mastocytosis was thus screened for a mutation of c-kit. This analysis revealed that four of four mastocytosis patients with an associated hematologic disorder with predominantly myelodysplastic features had an A-->T substitution at nt 2468 of c-kit mRNA that causes an Asp-816-->Val substitution. One of one patient examined who had mastocytosis with an associated hematologic disorder had the corresponding mutation in genomic DNA. Identical or similar amino acid substitutions in mast cell lines result in ligand-independent autophosphorylation of the c-kit receptor. This mutation was not identified in the patients within the other disease categories or in 67 of 67 controls. The identification of the point mutation Asp816Val in c-kit in patients with mastocytosis with an associated hematologic disorder provides insight not only into the pathogenesis of this form of mastocytosis but also into how hematopoiesis may become dysregulated and may serve to provide a means of confirming the diagnosis, assessing prognosis, and developing intervention strategies. 相似文献
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Kahal Hassan Kyrou Ioannis Uthman Olalekan A. Brown Anna Johnson Samantha Wall Peter D. H. Metcalfe Andrew Parr David G. Tahrani Abd A. Randeva Harpal S. 《Sleep & breathing》2020,24(1):339-350
Sleep and Breathing - Obesity is a common risk factor for polycystic ovary syndrome (PCOS) and obstructive sleep apnoea (OSA). Both PCOS and OSA are associated with increased risk of type 2... 相似文献
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Wen Yuan Chung Gianpiero Gravante Dhya Al‐Leswas Ali Arshad Roberto Sorge Chris C. Watson Cristina Pollard Matthew S. Metcalfe Ashley R. Dennison 《Artificial organs》2013,37(5):457-466
We already developed an ex vivo liver‐kidney model perfused for 6 h in which the kidney acted as a homeostatic organ to improve the circuit milieu compared to liver alone. In the current study, we extended the multiorgan perfusions to 24 h to evaluate the results and eventual pitfalls manifesting with longer durations. Five livers and kidneys were harvested from female pigs and perfused over 24 h. The extracorporeal circuit included a centrifugal pump, heat exchanger, and oxygenator. The primary end point of the study was the evaluation of the organ functions as gathered from biochemical and acid‐base parameters. In the combined liver‐kidney circuit, the organs survived and maintained an acceptable homeostasis for different lengths of time, longer for the liver (up to 19–23 h of perfusions) than the kidney (9–13 h of perfusions). Furthermore, glucose and creatinine values decreased significantly over time (from the 5th and 9th hour of perfusion onward). The addition of a kidney to the perfusion circuit improved the biochemical environment by removing excess products from ongoing metabolic processes. The consequence is a more physiological milieu that could improve results from future experimental studies. However, it is likely that long perfusions require some nutritional support over the hours to maintain the organ's vitality and functionality throughout the experiments. 相似文献
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Johanna Temme Anneke Kramer Kitty J. Jager Katharina Lange Frederick Peters Gerhard-Anton Müller Reinhard Kramar James G. Heaf Patrik Finne Runolfur Palsson Anna V. Reis?ter Andries J. Hoitsma Wendy Metcalfe Maurizio Postorino Oscar Zurriaga Julio P. Santos Pietro Ravani Faical Jarraya Enrico Verrina Friedo W. Dekker Oliver Gross 《Clinical journal of the American Society of Nephrology》2012,7(12):1969-1976