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81.
Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease 总被引:5,自引:0,他引:5
Nøjgaard C Johansen JS Christensen E Skovgaard LT Price PA Becker U;EMALD Group 《Journal of hepatology》2003,39(2):179-186
BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004). CONCLUSIONS: Serum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information. 相似文献
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Maria Wessman Inka Aho Kristina Thorsteinsson Merete Storgaard Isik S Johansen Suzanne Lunding Gitte Pedersen Anne‐Mette Lebech Pia Kivel Marie Helleberg Terese L Katzenstein Nina Weis 《Journal of the International AIDS Society》2015,18(1)
Introduction
As the human immunodeficiency virus (HIV)-positive population ages, issues concerning sexuality and fertility, among others, are becoming relevant. HIV is still surrounded by stigma and taboos, and there have been few studies conducted in industrialized settings concerning these questions. We therefore wanted to investigate the perception of sexuality and fertility in women living with HIV (WLWH) in an industrialized setting, using a questionnaire.Methods
WLWH were recruited at their regular outpatient clinic visits, at the major Departments of Infectious Diseases in Denmark and Finland, from January 2012 to October 2013. A questionnaire was developed, study participants were informed of the nature of study and, if they agreed to participate and signed a consent form, they filled in the questionnaire. Demographic information on the participants was obtained from patient files (in Finland) or from a national HIV cohort (in Denmark). Statistical analysis was performed using STATA®, version 11.Results
In total, 560 women were included in the study. The median age was 44 years. The majority were of white European origin, with fully suppressed HIV viral load, CD4 cell count >350 µL and mild or no symptoms of their HIV infection. A total of 62% were sexually active, stating condom use as their sole form of contraception. Of the sexually inactive women, one-third were in steady relationships. Eighty percent reported prior pregnancies, of which the majority had one or more children. Most children were born prior to the women''s HIV diagnosis and the mode of conception was predominantly natural. One-quarter of the participating women desired pregnancy, while more than half did not. The remaining quarter either stated that they already had the desired number of children or chose not to answer the question. Fourteen percent stated that their HIV diagnosis ended their wish for children; of these women, the median time of diagnosis was between 1995 and 1996. Pregnancy had been attempted unsuccessfully in one-quarter of study participants. The final question inquired what the risk of mother-to-child transmission was, with all precautions taken. Fifteen percent estimated the risk to be above two percent.Conclusions
In conclusion, the majority of WLWH in industrialized settings in Denmark and Finland have few HIV-related symptoms, are sexually active and have a strong desire for children. 相似文献83.
Kristine Færch Dorte Vistisen Nanna Borup Johansen Marit Eika Jørgensen 《Current diabetes reports》2014,14(6):1-8
Prediabetes, covering individuals with impaired fasting glycemia, impaired glucose tolerance, or high-risk HbA1c levels, is associated with a ~20 % increased risk of developing cardiovascular disease (CVD) compared with normoglycemic individuals. It is well-known that lifestyle or pharmacologic interventions can prevent diabetes in prediabetic people; however, the evidence is less clear regarding prevention of CVD. Most diabetes prevention trials have failed to show beneficial effects on CVD morbidity and mortality despite significant improvements of CVD risk factors in individuals with prediabetes. Another challenge is how to estimate CVD risk in prediabetic people. In general, prediction models for CVD do not take glucose levels or prediabetes status into account, thereby underestimating CVD risk in these high-risk individuals. More evidence within risk stratification and management of CVD risk in prediabetes is needed in order to recommend useful and effective strategies for early prevention of CVD. 相似文献
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Lena Hanberger Niels Birkebaek Ragnar Bjarnason Ann Kristin Drivvoll Anders Johansen Torild Skrivarhaug Arni V. Thorsson Ulf Samuelsson 《Journal of diabetes science and technology》2014,8(4):738-744
Background:In 2008 a Nordic collaboration was established between the quality registries in Denmark, Iceland, Norway, and Sweden to improve quality of care for children with diabetes. This study aimed to describe those registries and confirm that the registry variables are comparable. Selected variables were used to demonstrate outcome measurements.Methods:The organization of the registries and methodology are described. Cross-sectional data for patients between birth and 14.9 years with type 1 diabetes mellitus in 2009 (n = 6523) from 89 centers were analyzed. Variables were age, gender, and diabetic ketoacidosis at onset, together with age, gender, HbA1c, insulin regimen, and severe hypoglycemia at follow-up in 2009.Results:All 4 registries use a standardized registration at the onset of diabetes and at follow-up, conducted at the local pediatric diabetes centers. Methods for measuring HbA1c varied as did methods of registration for factors such as hypoglycemia. No differences were found between the outcomes of the clinical variables at onset. Significant variations were found at follow-up for mean HbA1c, the proportion of children with HbA1c < 57 mmol/mol (NGSP/DCCT 7.4%), (range 15-31%), the proportion with insulin pumps (range 34-55%), and the numbers with severe hypoglycemia (range 5.6-8.3/100 patient years).Conclusions:In this large unselected population from 4 Nordic countries, a high proportion did not reach their treatment target, indicating a need to improve the quality of pediatric diabetes care. International collaboration is needed to develop and harmonize quality indicators and offers possibilities to study large geographic populations, identify problems, and share knowledge. 相似文献
88.
Johanna I. Kiiski Liisa M. Pelttari Sofia Khan Edda S. Freysteinsdottir Inga Reynisdottir Steven N. Hart Hermela Shimelis Sara Vilske Anne Kallioniemi Johanna Schleutker Arto Leminen Ralf Bützow Carl Blomqvist Rosa B. Barkardottir Fergus J. Couch Kristiina Aittom?ki Heli Nevanlinna 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(42):15172-15177
Inherited predisposition to breast cancer is known to be caused by loss-of-function mutations in BRCA1, BRCA2, PALB2, CHEK2, and other genes involved in DNA repair. However, most families severely affected by breast cancer do not harbor mutations in any of these genes. In Finland, founder mutations have been observed in each of these genes, suggesting that the Finnish population may be an excellent resource for the identification of other such genes. To this end, we carried out exome sequencing of constitutional genomic DNA from 24 breast cancer patients from 11 Finnish breast cancer families. From all rare damaging variants, 22 variants in 21 DNA repair genes were genotyped in 3,166 breast cancer patients, 569 ovarian cancer patients, and 2,090 controls, all from the Helsinki or Tampere regions of Finland. In Fanconi anemia complementation gene M (FANCM), nonsense mutation c.5101C>T (p.Q1701X) was significantly more frequent among breast cancer patients than among controls [odds ratio (OR) = 1.86, 95% CI = 1.26–2.75; P = 0.0018], with particular enrichment among patients with triple-negative breast cancer (TNBC; OR = 3.56, 95% CI = 1.81–6.98, P = 0.0002). In the Helsinki and Tampere regions, respectively, carrier frequencies of FANCM p.Q1701X were 2.9% and 4.0% of breast cancer patients, 5.6% and 6.6% of TNBC patients, 2.2% of ovarian cancer patients (from Helsinki), and 1.4% and 2.5% of controls. These findings identify FANCM as a breast cancer susceptibility gene, mutations in which confer a particularly strong predisposition for TNBC.Breast cancer is the most common cancer affecting women worldwide. It is also the principal cause of death from cancer among women globally, accounting for 14% of all cancer deaths (1). The etiology of breast cancer is multifactorial, and the risk depends on various factors like age, family history, and reproductive, hormonal, or dietary factors. The majority of breast cancers are sporadic, but approximately 15% of cases show familial aggregation (2, 3). Since the identification of the first breast and ovarian cancer susceptibility genes breast cancer 1 and 2 (BRCA1 and BRCA2, respectively) by linkage analysis and positional cloning, several breast cancer susceptibility genes and alleles with different levels of risk and prevalence in the population have been recognized. BRCA1 and BRCA2 mutation carriers have more than 10-fold increased risk of breast cancer compared with women in the general population, and mutations in TP53, PTEN, STK11, and CDH1 have also been associated with a high lifetime risk of breast cancer in the context of rare inherited cancer syndromes (4). In addition, rare variants in genes such as checkpoint kinase 2 (CHEK2), ataxia telangiectasia mutated (ATM), and BRCA1 interacting helicase BRIP1, that confer a two- to fourfold increased risk, and in partner and localizer of BRCA2 (PALB2), with even higher risk estimates, have been found with candidate gene approaches (5, 6), and an increasing number of common low-risk loci with modest odds ratios (ORs; as much as 1.26-fold increased risk for heterozygous carriers) have been identified by genome-wide association studies (7).However, the major portion of hereditary breast cancer still remains unexplained, and many susceptibility loci are yet to be found. Exome sequencing combined with genotyping of the identified variants in case-control analysis is an effective method to recognize novel risk alleles, based on the assumption that disease-causing variants are rare and often accumulate in the protein-coding areas of the genome (8–10).Since the discovery that proteins encoded by the BRCA1 and BRCA2 breast/ovarian cancer susceptibility genes are directly involved in homologous recombination repair of DNA double-strand breaks, it has been evident that other genes involved in DNA repair are attractive breast cancer susceptibility candidates (4). Biallelic mutations in ATM gene cause rare ataxia telangiectasia disease and are associated with an increased risk for breast cancer as a result of improper DNA damage response (11). Fanconi anemia (FA) is a rare genetic disorder caused by biallelic mutations in FA genes that also participate in DNA repair. At least 15 FA genes have been identified (12). Patients with heterozygous mutations in certain FA genes have an elevated risk for various cancers, and monoallelic mutations in at least four of these genes [BRCA2, BRIP1, PALB2, and RAD51 paralog C (RAD51C)] are associated with an increased risk of breast or ovarian cancer (12, 13). Recurrent founder mutations in several cancer susceptibility genes, including the BRCA2, PALB2, and RAD51C FA genes, have been identified in the Finnish population (14–16). The PALB2 and RAD51C founder mutations have been detected at 2% frequency in Finnish breast or ovarian cancer families (15–17), whereas, in other populations, mutations in these genes are rare and often unique for each family. Founder effects in the isolated populations such as Finland or Iceland may enrich certain mutations and thus explain a significant proportion of all mutations in certain genes (18, 19). This provides an advantage in the search for novel susceptibility genes and alleles.In this study, we used exome sequencing to uncover previously unidentified recurrent breast or ovarian cancer predisposing variants in the Finnish population with a focus on DNA repair genes. Selected variants were further genotyped in a large case-control sample set. Our investigation revealed an association of a nonsense mutation (rs147021911) in an FA complementation gene, FANCM, with breast cancer, especially with triple-negative (TN) breast cancer (TNBC). 相似文献
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