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Sample records for chc patients genotype

  1. Methylenetetrahydrofolate reductase (MTHFR C677T polymorphism and high plasma homocysteine in chronic hepatitis C (CHC infected patients from the Northeast of Brazil

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    Silva Filipe

    2011-08-01

    Full Text Available Abstract Background/Aim Hyperhomocysteinemia due to Methylenetetrahydrofolate Reductase (MTHFR gene, in particular the C677T (Ala222Val polymorphism were recently associated to steatosis and fibrosis. We analyzed the frequency of MTHFR gene in a cross-sectional study of patients affected by Chronic Hepatitis C (CHC from Northeast of Brazil. Method One hundred seven-four untreated patients with CHC were genotyped for the C677T MTHFR. Genomic DNA was extracted from peripheral blood cells and the C677T MTHFR polymorphism was identified by PCR-RFLP. The homocysteine (Hcy levels were determined by chemiluminescence method. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and have current and past daily alcohol intake less than 100 g/week. Results Among subjects infected with CHC genotype non-1 the frequency of MTHFR genotypes TT was 9.8% versus 4.4% genotype 1 (p = 0.01. Nevertheless, association was found between the MTHFR genotype TT × CT/CC polymorphism and the degree of steatosis and fibrosis in both hepatitis C genotype (p Conclusion Our results indicate that plasma Hcy levels is highly prevalent in subjects with chronic hepatits C with steatosis regardless of HCV genotype and vitamin deficiency. The presence of genotype TT of MTHFR C677T polymorphism was more common in CHC genotype non-1 infected patient regardless of histopathological classification and genotype TT+CT frequencies were significant in the presence of fibrosis grade 1+2 and of steatosis in CHC infected patients from the northeast of Brazil regardless of HCV genotype. The genetic susceptibility of MTHFR C677T polymorphism should be confirmed in a large population.

  2. Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese Treatment-naÏve Patients Infected with Genotype 1b Hepatitis C Virus

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    Ye Wang

    2015-01-01

    Conclusions: The majority of genotype 1b CHC patients in China present a virus population carrying HCV DAAs RAVs. Pretreatment sequencing of HCV genome might need to be performed when patients infected with GT1b HCV receiving DAAs-containing regimens in China. Population sequencing would be quite quantified for the work.

  3. None of the six SNPs of IL28B could predict treatment responses in genotype 2 chronic HCV infected patients by propensity score matching analysis.

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    Wen-Juei Jeng

    Full Text Available BACKGROUND & AIMS: A combination of pegylated interferon-alpha and ribavirin (PR is the standard therapy for patients with chronic hepatitis C. The impact of polymorphism of interleukin-28B (IL28B on sustained virological response (SVR to PR has been well documented in patients with CHC genotype-1 (GT1, but it is controversial in genotype-2 (GT2 CHC patients. This study investigated the predictability of six single nucleotide polymorphisms (SNP of IL28B on the treatment responses of PR in patients with CHC GT2. METHOD: 197 CHC GT2 consecutive patients who received PR treatment in our prospective cohort were enrolled. Hepatitis C virus (HCV genotyping, quantification of HCV-RNA and genotyping of the ten SNPs of IL28B were performed. Six SNPs of IL28B were chosen for analysis. The propensity score matching (PSM analysis was applied using patients with CHC GT1 in another prospective cohort as a positive comparison to avoid covariate bias. RESULTS: The distribution of the six SNPs was similar in GT1 and GT2 patients. Five of these SNPs had strong association with treatment responses in GT1 but not in GT2 patients. After PSM analysis, these five SNPs still showed strong association with rapid virological response (RVR, cEVR and SVR in GT1 and had no influence in GT2 patients. Furthermore, rs12979860 and baseline viral load were the predictors for both RVR and SVR in GT1 patients. However, only baseline viral load could predict RVR and SVR in GT2 patients. In addition, in patients without RVR, rs12979860 was the only predictor for SVR in GT1 but no predictor for SVR was found in GT2. CONCLUSIONS: The genetic polymorphisms of IL28B had no impact on treatment responses in GT2 patients.

  4. Dicty_cDB: CHC251 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHC251 (Link to dictyBase) - - - Contig-U16381-1 - (Link to Original site) CHC2...51F 150 - - - - - - Show CHC251 Library CH (Link to library) Clone ID CHC251 (Link to dicty...iol.tsukuba.ac.jp/CSM/CH/CHC2-C/CHC251Q.Seq.d/ Representative seq. ID - (Link to ...Original site) Representative DNA sequence >CHC251 (CHC251Q) /CSM/CH/CHC2-C/CHC251Q.Seq.d/ CTGTTGGCCTACTGGTA...d/ 186 6e-47 CHC476 (CHC476Q) /CSM/CH/CHC4-D/CHC476Q.Seq.d/ 186 6e-47 CHC251 (CHC251Q) /CSM/CH/CHC2-C/CHC251Q.Seq.d/ 186 6e-47 CHC2

  5. A Protease Inhibitor with Induction Therapy with Natural Interferon-β in Patients with HCV Genotype 1b Infection.

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    Kishida, Yutaka; Imaizumi, Naohiko; Tanimura, Hirohisa; Kashiwamura, Shinichiro; Kashiwagi, Toru

    2016-03-09

    The restoration of innate immune responses has potential as a novel therapeutic strategy for chronic hepatitis C (CHC). We compared the efficacy and safety of induction therapy (IT) with natural interferon-β (n-IFN-β) followed by pegylated-IFN-α/ribavirin (PR) alone (group A, n = 30) and IT with a protease inhibitor (PI) (simeprevir or vaniprevir)/PR (group B, n = 13) in CHC patients with genotype 1b and high viral loads. During IT with nIFN-β, virologic response rates in group A and group B were 10% and 8% (p = 0.6792) at week 4, 30% and 16% (p = 0.6989) at week 12 and 47% and 20% (p = 0.0887) at week 24 respectively. During and after the treatment with PR alone or PI/PR, virologic response rates in groups A and B were 50% and 82% (p = 0.01535) at week 4, 53% and 91% (p = 0.006745) at week 8, 57% and 91% (p = 0.001126) at week 12, 57% and 100% (p < 0.001845) at the end of the treatment and 57% and 80% (p < 0.005166) after treatment cessation. IT with PI/PR linked to the restoration of innate immune response was tolerated well, overcame virological breakthrough, enhanced early virologic responses, and resulted in a sustained virologic response in difficult-to-treat CHC patients. IT with PI/PR is beneficial for treating difficult-to-treat CHC patients.

  6. A Protease Inhibitor with Induction Therapy with Natural Interferon-β in Patients with HCV Genotype 1b Infection

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    Yutaka Kishida

    2016-03-01

    Full Text Available The restoration of innate immune responses has potential as a novel therapeutic strategy for chronic hepatitis C (CHC. We compared the efficacy and safety of induction therapy (IT with natural interferon-β (n-IFN-β followed by pegylated-IFN-α/ribavirin (PR alone (group A, n = 30 and IT with a protease inhibitor (PI (simeprevir or vaniprevir/PR (group B, n = 13 in CHC patients with genotype 1b and high viral loads. During IT with nIFN-β, virologic response rates in group A and group B were 10% and 8% (p = 0.6792 at week 4, 30% and 16% (p = 0.6989 at week 12 and 47% and 20% (p = 0.0887 at week 24 respectively. During and after the treatment with PR alone or PI/PR, virologic response rates in groups A and B were 50% and 82% (p = 0.01535 at week 4, 53% and 91% (p = 0.006745 at week 8, 57% and 91% (p = 0.001126 at week 12, 57% and 100% (p < 0.001845 at the end of the treatment and 57% and 80% (p < 0.005166 after treatment cessation. IT with PI/PR linked to the restoration of innate immune response was tolerated well, overcame virological breakthrough, enhanced early virologic responses, and resulted in a sustained virologic response in difficult-to-treat CHC patients. IT with PI/PR is beneficial for treating difficult-to-treat CHC patients.

  7. Cost-effectiveness of narlaprevir in the chronic hepatitis C (genotype 1) therapy in treatment-naïve patients and relapsers

    OpenAIRE

    D. A. Gusev; A. V. Rudakova; A. N. Uskov; L. N. Konovalova; Yu. V. Lobzin

    2016-01-01

    In the treatment of chronic hepatitis C (CHC) protease inhibitors (PI) are actively used. The aim of this analysis was to evaluate the cost-effectiveness of narlaprevir and simeprevir in the CHC (genotype 1) therapy in treatment-naïve patients and relapsers.Material and methods. Analysis of the cost-effectiveness of simeprevir and narlaprevir was conducted from the perspective of the health care system based on QUEST-1, QUEST-2, ASPIRE and PIONEER clinical trials. The relative risk of achievi...

  8. Dicty_cDB: CHC270 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHC270 (Link to dictyBase) - - - Contig-U11649-1 CHC270P (Link to Original site) CHC2...70F 433 CHC270Z 724 CHC270P 1137 - - Show CHC270 Library CH (Link to library) Clone ID CHC2...e URL http://dictycdb.biol.tsukuba.ac.jp/CSM/CH/CHC2-C/CHC270Q.Seq.d/ Representative seq. ID CHC2...70P (Link to Original site) Representative DNA sequence >CHC270 (CHC270Q) /CSM/CH/CHC2-C/CHC2...-cDNA Score E Sequences producing significant alignments: (bits) Value CHC270 (CHC270Q) /CSM/CH/CHC2-C/CHC27

  9. Medical resource utilization and costs among Australian patients with genotype 1 chronic hepatitis C: results of a retrospective observational study.

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    McElroy, Heather J; Roberts, Stuart K; Thompson, Alex J; Angus, Peter W; McKenna, Sarah Jane; Warren, Emma; Musgrave, Sharon

    2017-01-01

    To evaluate medical resource utilization (MRU) and associated costs among Australian patients with genotype 1 chronic hepatitis C (GT1 CHC), including both untreated patients and those receiving treatment with first-generation protease inhibitor-based regimens (telaprevir, boceprevir with pegylated interferon and ribavirin). Medical records were reviewed for a stratified random sample of GT1 CHC patients first attending two liver clinics between 2011-2013 (principal population; PP), supplemented by all GT1 CHC patients attending one transplant clinic in the same period (transplant population; TP). CHC-related MRU and associated costs are reported for the PP by treatment status (treated/not treated) stratified by baseline fibrosis grade; and for the TP for the pre-transplant, year of transplant and post-transplant periods. A total 1636 patients were screened and 590 patients (36.1%) were included. Comprehensive MRU data were collected for 276 PP patients (F0-1 n = 59, F2 n = 58, F3 n = 53, F4 n = 106; mean follow-up = 17.3 months). Thirty-eight (13.8%) were treatment-experienced prior to enrolment; 55 (19.9%) received triple therapy during the study. Data were collected for 112 TP patients (mean follow-up = 29.9 months), 33 (29.5%) received a transplant during the study, and 51 (45.5%) beforehand. The annual direct medical costs, excluding drug costs, were higher among treated PP vs untreated PP (AU$: $1,954 vs $1,202); and year of transplant TP vs pre-/post-transplant TP (AU$: pre-transplant $32,407, transplant $155,138, post-transplant $7,358). To aid interpretation of results, note that only patients with GT1 CHC who are actively managed are included, and MRU data were collected specifically from liver outpatient clinics. That said, movement of patients between hospitals is rare, and any uncaptured MRU is expected to be minimal. CHC-related MRU increases substantially with disease severity. These real-world MRU data for GT1 CHC will be

  10. The CHC22 clathrin-GLUT4 transport pathway contributes to skeletal muscle regeneration.

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    Hoshino, Sachiko; Sakamoto, Kazuho; Vassilopoulos, Stéphane; Camus, Stéphane M; Griffin, Christine A; Esk, Christopher; Torres, Jorge A; Ohkoshi, Norio; Ishii, Akiko; Tamaoka, Akira; Funke, Birgit H; Kucherlapati, Raju; Margeta, Marta; Rando, Thomas A; Brodsky, Frances M

    2013-01-01

    Mobilization of the GLUT4 glucose transporter from intracellular storage vesicles provides a mechanism for insulin-responsive glucose import into skeletal muscle. In humans, clathrin isoform CHC22 participates in formation of the GLUT4 storage compartment in skeletal muscle and fat. CHC22 function is limited to retrograde endosomal sorting and is restricted in its tissue expression and species distribution compared to the conserved CHC17 isoform that mediates endocytosis and several other membrane traffic pathways. Previously, we noted that CHC22 was expressed at elevated levels in regenerating rat muscle. Here we investigate whether the GLUT4 pathway in which CHC22 participates could play a role in muscle regeneration in humans and we test this possibility using CHC22-transgenic mice, which do not normally express CHC22. We observed that GLUT4 expression is elevated in parallel with that of CHC22 in regenerating skeletal muscle fibers from patients with inflammatory and other myopathies. Regenerating human myofibers displayed concurrent increases in expression of VAMP2, another regulator of GLUT4 transport. Regenerating fibers from wild-type mouse skeletal muscle injected with cardiotoxin also showed increased levels of GLUT4 and VAMP2. We previously demonstrated that transgenic mice expressing CHC22 in their muscle over-sequester GLUT4 and VAMP2 and have defective GLUT4 trafficking leading to diabetic symptoms. In this study, we find that muscle regeneration rates in CHC22 mice were delayed compared to wild-type mice, and myoblasts isolated from these mice did not proliferate in response to glucose. Additionally, CHC22-expressing mouse muscle displayed a fiber type switch from oxidative to glycolytic, similar to that observed in type 2 diabetic patients. These observations implicate the pathway for GLUT4 transport in regeneration of both human and mouse skeletal muscle, and demonstrate a role for this pathway in maintenance of muscle fiber type. Extrapolating

  11. Dicty_cDB: CHC222 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHC222 (Link to dictyBase) - - - Contig-U16381-1 - (Link to Original site) CHC2...22F 152 - - - - - - Show CHC222 Library CH (Link to library) Clone ID CHC222 (Link to dicty...iol.tsukuba.ac.jp/CSM/CH/CHC2-A/CHC222Q.Seq.d/ Representative seq. ID - (Link to ...Original site) Representative DNA sequence >CHC222 (CHC222Q) /CSM/CH/CHC2-A/CHC222Q.Seq.d/ CACTGTTGGCCTACTGG...NA Score E Sequences producing significant alignments: (bits) Value CHC222 (CHC222Q) /CSM/CH/CHC2-A/CHC222Q.

  12. Direct-acting Antiviral Agents Resistance-associated Polymorphisms in Chinese Treatment-na(i)ve Patients Infected with Genotype 1b Hepatitis C Virus

    Institute of Scientific and Technical Information of China (English)

    Ye Wang; Hui-Ying Rao; Xing-Wang Xie; Lai Wei

    2015-01-01

    Background:It has been reported that several baseline polymorphisms of direct-acting antivirals (DAAs) agents resistance-associated variants (RAVs) would affect the treatment outcomes of patients chronically infected with hepatitis C virus (CHC).The aim of this study is to investigate the prevalence of DAAs RAVs in treatment-na(i)ve GT1b CHC patients.Methods:Direct sequencing and ultra-deep sequencing of the HCV NS3,NS5A,and NS5B gene were performed in baseline serum samples of treatment-ha(i)ve patients infected with genotype lb hepatitis C virus (HCVs).Results:One hundred and sixty CHC patients were studied.Complete sequence information was obtained for 145 patients (NS3),148 patients (NS5A),and 137 patients (NS5B).Treatment-failure associated variants of DAAs were detected:56.6% (82/145) of the patients presented S122G for simeprevir (NS3 protease inhibitor);10.1% (14/148) of the patients presented Y93H for daclatasvir and ledipasvir (NS5A protein inhibitors);94.2% (129/137) of the patients presented C316N for sofosbuvir (NS5B polymerase inhibitor).Nearly,all of the DAAs RAVs detected by ultra-deep sequencing could be detected by direct sequencing.Conclusions:The majority of genotype lb CHC patients in China present a virus population carrying HCV DAAs RAVs.Pretreatment sequencing of HCV genome might need to be performed when patients infected with GTlb HCV receiving DAAs-containing regimens in China.Population sequencing would be quite quantified for the work.

  13. The CHC22 clathrin-GLUT4 transport pathway contributes to skeletal muscle regeneration.

    Directory of Open Access Journals (Sweden)

    Sachiko Hoshino

    Full Text Available Mobilization of the GLUT4 glucose transporter from intracellular storage vesicles provides a mechanism for insulin-responsive glucose import into skeletal muscle. In humans, clathrin isoform CHC22 participates in formation of the GLUT4 storage compartment in skeletal muscle and fat. CHC22 function is limited to retrograde endosomal sorting and is restricted in its tissue expression and species distribution compared to the conserved CHC17 isoform that mediates endocytosis and several other membrane traffic pathways. Previously, we noted that CHC22 was expressed at elevated levels in regenerating rat muscle. Here we investigate whether the GLUT4 pathway in which CHC22 participates could play a role in muscle regeneration in humans and we test this possibility using CHC22-transgenic mice, which do not normally express CHC22. We observed that GLUT4 expression is elevated in parallel with that of CHC22 in regenerating skeletal muscle fibers from patients with inflammatory and other myopathies. Regenerating human myofibers displayed concurrent increases in expression of VAMP2, another regulator of GLUT4 transport. Regenerating fibers from wild-type mouse skeletal muscle injected with cardiotoxin also showed increased levels of GLUT4 and VAMP2. We previously demonstrated that transgenic mice expressing CHC22 in their muscle over-sequester GLUT4 and VAMP2 and have defective GLUT4 trafficking leading to diabetic symptoms. In this study, we find that muscle regeneration rates in CHC22 mice were delayed compared to wild-type mice, and myoblasts isolated from these mice did not proliferate in response to glucose. Additionally, CHC22-expressing mouse muscle displayed a fiber type switch from oxidative to glycolytic, similar to that observed in type 2 diabetic patients. These observations implicate the pathway for GLUT4 transport in regeneration of both human and mouse skeletal muscle, and demonstrate a role for this pathway in maintenance of muscle fiber

  14. Dicty_cDB: CHC836 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ucing significant alignments: (bits) Value CHC836 (CHC836Q) /CSM/CH/CHC8-B/CHC836Q.Seq.d/ 170 3e-42 SFF285 (...te 2009. 4. 4 Homology vs DNA Score E Sequences producing significant alignments: (bits) Value...ificant alignments: (bits) Value U61987_1( U61987 |pid:none) Dictyostelium discoideum phosphoprotei... 37 0.

  15. Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

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    M Hashem Abdel

    2011-11-01

    Full Text Available Abstract Background Hepatitis C virus (HCV is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4 in the world; this study investigated effects of HCV genotype-4 (HCV-4 on prevalence of insulin resistance in chronic hepatitis C (CHC and HCC in Egyptian patients. Methods Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples. Results HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23. Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p Conclusions IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.

  16. Distribution of interferon lambda-3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: Analysis from the PREDICT and CHARIOT studies.

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    Roberts, Stuart K; Mitchell, Joanne; Leung, Reynold; Booth, David; Bollipo, Steven; Ostapowicz, George; Sloss, Andrew; McCaughan, Geoffrey W; Dore, Gregory J; Thompson, Alexander; Crawford, Darrell Hg; Sievert, William; Weltman, Martin; Cheng, Wendy; George, Jacob

    2014-01-01

    The aim of this study was to examine the distribution of interferon lambda-3 (IFN-λ3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN-λ3 genotype frequency among the different ethnic populations. This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment. IFN-λ3 single nucleotide polymorphisms were genotyped by the Applied Biosystems's Taqman single nucleotide polymorphism genotyping assay. Between May 2012 and June 2012, 1132 patients were recruited from 38 treatment clinics across Australia. Also, 561 subjects from the CHARIOT (collaborative group hepatitis C study using high dose Pegasys RBV Induction dose in genotype one) study of high-dose interferon who had baseline serum available were retrospectively tested. The overall frequency of IFN-λ3 rs12979860 CC/CT/TT genotypes was 36%, 52%, and 12%, and that of rs8099917 TT/TG/GG genotypes was 54%, 41%, and 5%, respectively. The prevalence of the favorable IFN-λ3 rs12979860 CC and rs8099917 TT genotypes in Causcasians, Asians, Aboriginals, Maori/Pacific Islanders, and Mediterraneans was 32% and 52%, 80% and 86%, 33% and 63%, 77% and 88%, and 19% and 29%, respectively. Compared with Caucasians, the frequency of IFN-λ3 CC was significantly higher among Asians (P < 0.0001) and Maori/Pacific Islander subjects (P < 0.0001). The distribution of IFN-λ3 polymorphisms among untreated patients with Gt1 CHC in Australia appears similar to that reported from North America. The frequency of the favorable response alleles varies considerably according to ethnicity, being more common in self-reported Asians and Maori/Pacific Islanders than Caucasians, Aboriginals, and Mediterraneans. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty

  17. The Efficacy and Safety of 12 Weeks of Sofosbuvir and Ledipasvir versus Sofosbuvir, Ledipasvir, and Ribavirin in Patients with Chronic Hepatitis C, Genotype 1, Who Have Cirrhosis and Have Failed Prior Therapy: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Fenton, Carol; James, Matthew; Tang, Karen L.

    2017-01-01

    Background. The recommended therapy for patients with chronic hepatitis C (CHC), genotype 1, who have cirrhosis and have failed prior therapy is 12 weeks of sofosbuvir (SOF), ledipasvir (LDV), and ribavirin (RBV). This recommendation is based on expert opinion, and the efficacy of 12 weeks of SOF/LDV compared to SOF/LDV/RBV in this patient population has not yet been established. Methods. We conducted a systematic review and meta-analysis. Two investigators independently searched electronic databases and relevant conference proceedings for randomized controlled trials comparing rates of sustained virologic response 12 weeks after therapy (SVR12) when using 12 weeks of SOF/LDV versus 12 weeks of SOF/LDV/RBV in patients with CHC, genotype 1, who have cirrhosis and failed previous therapy. Results. Our search strategy yielded 596 studies of which four met criteria for inclusion. The pooled RR of not achieving SVR12 with SOF/LDV versus SOF/LDV/RBV was 1.21 (95% CI: 0.42–3.48). Adverse events were lower in the SOF/LDV compared to the SOF/LDV/RBV arms (pooled RR: 0.11, 95% CI: 0.04–0.29). Conclusions. Our findings suggest that 12 weeks of SOF/LDV cannot be considered noninferior to 12 weeks of SOF/LDV/RBV to achieve SVR12 in patients with CHC who have cirrhosis and failed prior therapy. PMID:28367429

  18. Hepatic expression levels of interferons and interferon-stimulated genes in patients with chronic hepatitis C: A phenotype-genotype correlation study.

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    Noureddin, M; Rotman, Y; Zhang, F; Park, H; Rehermann, B; Thomas, E; Liang, T J

    2015-01-01

    IFNL4 is linked to hepatitis C virus treatment response and type III interferons (IFNs). We studied the functional associations among hepatic expressions of IFNs and IFN-stimulated genes (ISGs), and treatment response to peginterferon and ribavirin. Type I IFNs (IFNA1, IFNB1), type II (IFNG), type III (IFNL1, IFNL2/3), IFNL4 and ISG hepatic expressions were measured by qPCR from in 65 chronic hepatitis C (CHC) patients whose IFNL4-associated rs368234815 and IFNL3-associated rs12989760 genotype were determined. There was a robust correlation of hepatic expression within type I and type III IFNs and between type III IFNs and IFNL4 but no correlation between other IFN types. Expression of ISGs correlated with type III IFNs and IFNL4 but not with type I IFNs. Levels of ISGs and IFNL2/3 mRNAs were lower in IFNL3 rs12979860 CC patients compared with non-CC patients, and in treatment responders, compared with nonresponders. IFNL4-ΔG genotype was associated with high ISG levels and nonresponse. Hepatic levels of ISGs in CHC are associated with IFNL2/3 and IFNL4 expression, suggesting that IFNLs, not other types of IFNs, drive ISG expression. Hepatic IFNL2/3 expression is functionally linked to IFNL4 and IFNL3 polymorphisms, potentially explaining the tight association among ISG expression and treatment response.

  19. The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C.

    Science.gov (United States)

    Domagalski, Krzysztof; Pawłowska, Małgorzata; Kozielewicz, Dorota; Dybowska, Dorota; Tretyn, Andrzej; Halota, Waldemar

    2015-01-01

    The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer's modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007). We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004). Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients.

  20. The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C.

    Directory of Open Access Journals (Sweden)

    Krzysztof Domagalski

    Full Text Available The strong impact of interleukin 28B (IL28B polymorphisms on sustained virological response (SVR after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer's modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P 0.05; in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007. We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004. Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients.

  1. Baseline factors and very early viral response (week 1) for predicting sustained virological response in telaprevir-based triple combination therapy for Japanese genotype 1b chronic hepatitis C patients: a multicenter study.

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    Shimada, Noritomo; Toyoda, Hidenori; Tsubota, Akihito; Ide, Tatsuya; Takaguchi, Koichi; Kato, Keizo; Kondoh, Masaki; Matsuyama, Kazuhiro; Kumada, Takashi; Sata, Michio

    2014-11-01

    Genetic polymorphisms near Interleukin 28B (IL28B) (rs8099917) and a rapid virological response (RVR) have been reported as predictors for a sustained virological response (SVR) to telaprevir (TVR)-based triple combination therapy. However, the association between SVR and viral kinetics earlier than week 4 after initiation of therapy remains unclear. Thus, we evaluated the SVR prediction ability of baseline factors and reduced hepatitis C virus (HCV) RNA levels at week 1 after the initiation of TVR-based therapy in Japanese genotype-1b chronic hepatitis C (CHC) patients. A total of 156 Japanese CHC patients received a 24-week regimen of TVR-based therapy. Baseline factors and reduction in HCV RNA levels at weeks 1 and 4 after the initiation of therapy were analyzed for SVR prediction. Multiple logistic regression analysis for SVR in TVR-based therapy identified the IL28B TT genotype, a reduction of ≥ 4.7 log10 IU/mL in HCV RNA levels at week 1, RVR, and treatment-naïve/relapse. Whereas the SVR rate was higher than 90 % regardless of the reduction in HCV RNA levels at week 1 in patients with the TT genotype, a reduction of ≥ 4.7 log10 IU/mL in HCV RNA levels at week 1 was the strongest predictor of SVR in patients with the non-TT genotype, as determined by multiple logistic regression analysis (P = 0.0043). The IL28B TT genotype is the most important baseline factor for predicting SVR, and a ≥ 4.7 log10 IU/mL reduction in HCV RNA at week 1 is a useful very early on-treatment predictor of SVR, especially in the non-TT genotype.

  2. Serum Islet Cell Autoantibodies During Interferon α Treatment in Patients With HCV-Genotype 4 Chronic Hepatitis

    Directory of Open Access Journals (Sweden)

    Gamal Badra

    2006-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection is a leading cause of end-stage liver disease worldwide and HCV genotype 4 (HCV4 is predominant in African and Middle Eastern countries. It is well established that interferon-α (IFNa treatment for HCV may trigger serum autoantibodies against pancreatic islet cells (ICA in a subgroup of patients. Available data on the incidence of ICA during IFNa therapy for chronic HCV4 infection are not conclusive. We investigated the appearance of ICA in 40 naïve Egyptian patients (38 males, 32 ± 6 years with histologically defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million U/week for 24 weeks. Serum samples were collected at baseline and following IFNa therapy and ICA were detected using indirect immunofluorescence. Baseline evaluation indicated that 2/40 (5% patients had detectable serum ICA. After the completion of the treatment scheme, 12/38 (32% previously ICA negative patients became ICA positive; however, no patient developed impaired glucose tolerance (IGT or diabetes during follow-up. In conclusion, we submit that IFNa treatment for chronic hepatitis C (CHC may induce serum ICA in one-third of Egyptian patients with HCV4. These autoantibodies, however, do not lead to alterations in glucose metabolism.

  3. Prevalence of abnormal glycometabolism in patients with chronic hepatitis C and related risk factors in China

    Institute of Scientific and Technical Information of China (English)

    WANG Li-fen; WU Chi-hong; SHAN Yuan; FAN Xiao-hong; HUO Na; LU Hai-ying; XU Xiao-yuan

    2011-01-01

    Background An epidemiologic link between hepatitis C virus (HCV) and abnormal glycometabolism had been established.This study was designed to investigate the prevalence of type 2 diabetes rnellitus and insulin resistance,and to explore the relation between insulin resistance and hepatitis C virus genotype,serum hepatitis C virus-RNA level in chronic hepatitis C(CHC) patients.Methods Three hundred and fifty-nine consecutive patients (CHC,n=296;chronic hepatitis B (CHB),n=63) were evaluated.HCV genotyping was performed by restriction fragment method and serum hepatitis C virus-RNA quantified PCR for all CHC patients in the baseline serum.Fasting levels of insulin and glucose were measured in all patients and the homeostatic assessment of insulin resistance was calculated in the baseline serum.Results Type 2 diabetes mellitus was diagnosed in 15.5% of 296 CHC patients.Insulin resistance was present in 23.8% of the 235 nondiabetic CHC patients,in 23.1% of the 182 nondiabetic and noncirrhotic CHC patients,and associated with high serum HCV RNA level (OR: 1.754;95% CI:1.207-2.548,P=0.003) and age >40 years (OR.3.542;95% CI:1.257-9.978,P=0.017).Insulin resistance was less frequent in CHB than in matched CHC (7.9% vs.21.4%respectively,P <0.0001).Conclusion The incidence of insulin resistance in CHC was significantly higher than that in CHB patients,associated with high serum HCV RNA level and age >40 years.

  4. Interferon-free regimens in patients with hepatitis C infection and renal dysfunction or kidney transplantation

    Science.gov (United States)

    Cholongitas, Evangelos; Pipili, Chrysoula; Papatheodoridis, George V

    2017-01-01

    Treatment of patients with chronic kidney disease (CKD) and chronic hepatitis C (CHC) differs from that used in the general CHC population mostly when glomerular filtration rate (GFR) is below 30 mL/min, as sofosbuvir, the backbone of several current regimens, is officially contraindicated. Given that ribavirin free regimens are preferable in CKD, elbasvir/grazoprevir is offered in CHC patients with genotype 1 or 4 and ombitasvir/paritaprevir and dasabuvir in genotype 1b for 12 wk. Although regimens containing peginterferon with or without ribavirin are officially recommended for patients with CKD and genotype 2, 3, 5, 6, such regimens are rarely used because of their low efficacy and the poor safety and tolerance profile. In this setting, especially in the presence of advanced liver disease, sofosbuvir-based regimens are often used, despite sofosbuvir contraindication. It seems to have good overall safety with only 6% or 3.4% of CKD patients to discontinue therapy or develop serious adverse events without drug discontinuation. In addition, sustained virological response (SVR) rates with sofosbuvir based regimens in CKD patients appear to be comparable with SVR rates in patients with normal renal function. Treatment recommendations for kidney transplant recipients are the same with those for patients with CHC, taking into consideration potential drug-drug interactions and baseline GFR before treatment initiation. This review summarizes recent data on the current management of CHC in CKD patients highlighting their strengths and weaknesses and determining their usefulness in clinical practice. PMID:28217256

  5. ABO genotyping in leukemia patients reveals new ABO variant alleles

    OpenAIRE

    Novaretti,M.C.Z.; DOMINGUES, A. E.; MANHANI, R.; Pinto, E M; Dorlhiac-Llacer, P.E.; Chamone, D.A.F.

    2008-01-01

    The ABO blood group is the most important blood group system in transfusion medicine and organ transplantation. To date, more than 160 ABO alleles have been identified by molecular investigation. Almost all ABO genotyping studies have been performed in blood donors and families and for investigation of ABO subgroups detected serologically. The aim of the present study was to perform ABO genotyping in patients with leukemia. Blood samples were collected from 108 Brazilian patients with chronic...

  6. Superoxide Dismutase and Catalase Genotypes in Pediatric Migraine Patients.

    Science.gov (United States)

    Saygi, Semra; Erol, İlknur; Alehan, Füsun; Yalçın, Yaprak Yılmaz; Kubat, Gözde; Ataç, Fatma Belgin

    2015-10-01

    This study compared superoxide dismutase (SOD) and catalase (CAT) alleles in 97 consecutive children and adolescents with migraine to 96 healthy children and adolescents. Isolated genomic DNA was used as a template for SOD1 (35 A/C), SOD2 16 C/T, and CAT2 [(-262 C/T) and (-21 A/T)] allele genotyping. The SOD2 16 C/T genotype and C allele frequency differed significantly between controls and migraine (P = .047; P = .038). CAT -21 AA genotype and A allele frequency were significantly higher in both migraine with aura patients (P = .013; P = .004) and migraine without aura patients (P = .003; P = .001) compared to controls. To our knowledge, this is the first demonstration of differences in SOD and CAT genotypes between pediatric migraine patients and age-matched controls. Further studies on the functional implications of these genetic variants on neural antioxidant capacity and the use of antioxidant modulators for migraine treatment are warranted.

  7. Shortening of treatment duration in patients with chronic hepatitis C genotype 2 and 3 - impact of ribavirin dose - a randomized multicentre trial

    Directory of Open Access Journals (Sweden)

    Bischof Martin

    2011-06-01

    Full Text Available Abstract Background Chronic hepatitis C (CHC Patients, infected with genotype (GT 2 or 3 are treated with Peg-IFN and ribavirin (RBV (800 mg/day for 24 weeks. Treatment duration can be shortened to 12-16 weeks if a higher dose of RBV (1.000/1.200 mg/day was used without considerable loss of responsiveness or increased risk of relapse. Previously we have shown that in patients with CHC, GT 2/3 RBV can be reduced to 400 mg/day if administered for 24 weeks without an increase in relapse rates. Therefore we investigated the efficacy of a reduced RBV dosage of 400 mg/day with shorter treatment duration (16 weeks. Methods Treatment naïve patients with CHC, GT 2/3 were randomized to receive 180 μg peginterferonα2a/week in combination with either 800 (group C or 400 mg/d (group D for 16 weeks. The primary endpoint was SVR. Results 12 months after the first patient was randomized a inferior outcome of group D as compared to group C was noted, therefore the study was terminated. At study termination 89 patients were enrolled (group C: 31, D: 51. The SVR rate was statistically different in the two study groups with 51.6% in group C and 28.4% in group D (p = 0.038. Patients with low viral load had higher SVR rates (C: 67%, D: 33% than those with high viral load (C: 33%, D: 21%. Conclusion Both treatment duration and the dose of RBV play a major role to optimize outcome of patients with GT3. If one intends to shorten the treatment weight based RBV dose should be used, if lower RBV doses are used patients should be treated for at least 24 weeks as. A treatment regimen with a reduced RBV dosage and shortened treatment duration is associated with low SVR rates due to high relapse rates. Trial registration NCT01258101

  8. Determinant Factors of the Direct Medical Costs Associated with Genotype 1 Hepatitis C Infection in Treatment-Experienced Patients.

    Science.gov (United States)

    Akpo, Essè Ifèbi Hervé; Sbarigia, Urbano; Wan, George; Kleintjens, Joris

    2015-12-01

    Limited evidence is available on predictors of medical resource utilization (MRU) and related direct costs, especially in treatment-experienced patients infected with genotype 1 hepatitis C virus (HCV). This study aimed at investigating patient and treatment characteristics that predict MRU and related non-drug costs in treatment-experienced patients with chronic hepatitis C (CHC) treated with simeprevir (SMV) or telapravir (TVR) in combination with pegylated interferon and ribavirin (PegIFN/R). A total of 709 patients who completed the 72-week ATTAIN trial were included in the study. Cost data were analysed from the UK NHS perspective. Descriptive statistics and regression analyses were used to determine patterns and predictors of total MRU-related costs associated with SMV/PegIFN/R and TVR/PegIFN/R. Independent predictors for total MRU-related costs were age, region and the following interaction terms: (1) gender × F3-F4 METAVIR score × baseline viral load (BLVL), (2) body mass index (BMI) × F3-F4 METAVIR score × prior response to PegIFN/R and (3) gender × achievement of SVR at 12 weeks (SVR12) × BLVL. A F3-F4 METAVIR score was a stronger predictor of total MRU-related costs than SVR12. Predictors of adverse events included older age, female gender, low BMI, TVR/PegIFN/R and SVR12. Wilcoxon rank sum test revealed comparable total MRU-related costs between SMV/PegIFN/R and TVR/PegIFN/R. To the best of our knowledge, this study is the first to describe the relationship between commonly admitted predictors of MRU-related costs and their joint effect on total MRU-related costs in treatment-experienced patients with CHC. The identified predictors of MRU-related costs suggest that significant treatment costs can be avoided by starting treatment early before the disease progresses. Furthermore, adverse events seem to be the most important factor to take into consideration for the choice of treatment, especially when therapeutic options are associated with similar

  9. IS CHC student surface learner A cross-cultural perspective

    Institute of Scientific and Technical Information of China (English)

    李佩绮

    2008-01-01

    In the past decades, the "CH"(Confucian Heritage Culture)learner phenomenon had aroused the interest of sociologists, educators and psychologists. Examination orientation, achievement orientation, use of repetitive learning, synthesis of memorization and understanding, and the use of recitation to bring about sharp focus for better understanding were some of the themes of these researches. This paper will explain what the general paradox of CHC learners is and how cultural difference can affect students' motivation for learning according to Chen and Stevenson's model of cultural influence, and discuss the major misconception of CHC learners' study approach.

  10. On the interpretation of the CHC factor Gc

    NARCIS (Netherlands)

    K.-J. Kan; R.A. Kievit; C. Dolan; H. van der Maas

    2011-01-01

    On the one hand, the factors Gf and Gc in the Cattell-Horn-Carroll (CHC) model of intelligence are hypothesized to represent individual differences in unique psychological or biological capacities. On the other hand, they are interpreted as representing the theoretical variables fluid and crystalliz

  11. Childhood Pompe disease: clinical spectrum and genotype in 31 patients

    NARCIS (Netherlands)

    Capelle, C.I. van; Meijden, J.C. van der; Hout, J.M. van den; Jaeken, J.; Baethmann, M.; Voit, T.; Kroos, M.A.; Derks, T.G.; Rubio-Gozalbo, M.E.; Willemsen, M.A.A.P.; Lachmann, R.H.; Mengel, E.; Michelakakis, H.; Jongste, J.C. de; Reuser, A.J.; Ploeg, A.T. van der

    2016-01-01

    BACKGROUND: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the Net

  12. Childhood Pompe disease: Clinical spectrum and genotype in 31 patients

    NARCIS (Netherlands)

    C.I. van Capelle (Carine); J.C. van der Meijden (J.); J.M.P. van den Hout (Johanna); J. Jaeken; M. Baethmann; T. Voit; M.A. Kroos (Marian); T.G.J. Derks (Terry G J); M.E. Rubio-Gozalbo (Estela); M.A. Willemsen (Michél); R. Lachmann (Robin); E. Mengel; H. Michelakakis (Helen); J.C. de Jongste (Johan); A.J.J. Reuser (Arnold); A.T. van der Ploeg (Ans)

    2016-01-01

    textabstractBackground: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotter

  13. Childhood Pompe disease : clinical spectrum and genotype in 31 patients

    NARCIS (Netherlands)

    van Capelle, C I; van der Meijden, J C; van den Hout, J M P; Jaeken, J; Baethmann, M; Voit, T; Kroos, M A; Derks, T G J; Rubio-Gozalbo, M E; Willemsen, M A; Lachmann, R H; Mengel, E; Michelakakis, H; de Jongste, J C; Reuser, A J J; van der Ploeg, A T

    2016-01-01

    BACKGROUND: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the Net

  14. Childhood Pompe disease: Clinical spectrum and genotype in 31 patients

    NARCIS (Netherlands)

    C.I. van Capelle (Carine); J.C. van der Meijden (J.); J.M.P. van den Hout (Johanna); J. Jaeken; M. Baethmann; T. Voit; M.A. Kroos (Marian); T.G.J. Derks (Terry G J); M.E. Rubio-Gozalbo (Estela); M.A. Willemsen (Michél); R. Lachmann (Robin); E. Mengel; H. Michelakakis (Helen); J.C. de Jongste (Johan); A.J.J. Reuser (Arnold); A.T. van der Ploeg (Ans)

    2016-01-01

    textabstractBackground: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in

  15. Childhood Pompe disease: clinical spectrum and genotype in 31 patients

    NARCIS (Netherlands)

    Capelle, C.I. van; Meijden, J.C. van der; Hout, J.M. van den; Jaeken, J.; Baethmann, M.; Voit, T.; Kroos, M.A.; Derks, T.G.; Rubio-Gozalbo, M.E.; Willemsen, M.A.A.P.; Lachmann, R.H.; Mengel, E.; Michelakakis, H.; Jongste, J.C. de; Reuser, A.J.; Ploeg, A.T. van der

    2016-01-01

    BACKGROUND: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the

  16. Childhood Pompe disease : clinical spectrum and genotype in 31 patients

    NARCIS (Netherlands)

    van Capelle, C I; van der Meijden, J C; van den Hout, J M P; Jaeken, J; Baethmann, M; Voit, T; Kroos, M A; Derks, T G J; Rubio-Gozalbo, M E; Willemsen, M A; Lachmann, R H; Mengel, E; Michelakakis, H; de Jongste, J C; Reuser, A J J; van der Ploeg, A T

    2016-01-01

    Background: As little information is available on children with non-classic presentations of Pompe disease, we wished to gain knowledge of specific clinical characteristics and genotypes. We included all patients younger than 18 years, who had been evaluated at the Pompe Center in Rotterdam, the

  17. Hepatitis B virus genotypes and resistance mutations in patients under long term lamivudine therapy: characterization of genotype G in Brazil

    Directory of Open Access Journals (Sweden)

    Brandão Carlos E

    2008-01-01

    Full Text Available Abstract Background Lamivudine is an oral nucleoside analogue widely used for the treatment of chronic hepatitis B. The main limitation of lamivudine use is the selection of resistant mutations that increases with time of utilization. Hepatitis B virus (HBV isolates have been classified into eight genotypes (A to H with distinct geographical distributions. HBV genotypes may also influence pathogenic properties and therapeutic features. Here, we analyzed the HBV genotype distribution and the nature and frequency of lamivudine resistant mutations among 36 patients submitted to lamivudine treatment for 12 to 84 months. Results Half of the patients were homosexual men. Only 4/36 (11% patients were HBV DNA negative. As expected for a Brazilian group, genotypes A (24/32 positive individuals, 75%, D (3/32, 9.3% and F (1/32, 3% were present. One sample was from genotype C, which is a genotype rarely found in Brazil. Three samples were from genotype G, which had not been previously detected in Brazil. Lamivudine resistance mutations were identified in 20/32 (62% HBV DNA positive samples. Mean HBV loads of patients with and without lamivudine resistance mutations were not very different (2.7 × 107 and 6.9 × 107 copies/mL, respectively. Fifteen patients showed the L180M/M204V lamivudine resistant double mutation. The triple mutant rt173V/180M/204V, which acts as a vaccine escape mutant, was found in two individuals. The three isolates of genotype G were entirely sequenced. All three showed the double mutation L180M/M204V and displayed a large genetic divergence when compared with other full-length genotype G isolates. Conclusion A high (55% proportion of patients submitted to long term lamivudine therapy displayed resistant mutations, with elevated viral load. The potential of transmission of such HBV mutants should be monitored. The identification of genotypes C and G, rarely detected in South America, seems to indicate a genotype distribution different

  18. Is pegylated interferon superior to interferon, with ribavarin, in chronic hepatitis C genotypes 2/3?

    Institute of Scientific and Technical Information of China (English)

    Ijaz S Jamall; Shafaq Yusuf; Maimoona Azhar; Selene Jamall

    2008-01-01

    Over the past decade,significant improvements have been made in the treatment of chronic hepatitis C(CHC),especially with the introduction of combined therapy using both interferon and ribavarin.The optimal dose and duration of treatment is still a matter of debate and,importantly,the efficacy of this combined treatment varies with the viral genotype responsible for infection.In general,patients infected with viral genotypes 2 or 3 more readily achieve a sustained viral response than those infected with viral genotype 1.The introduction of a pegylated version of interferon in the past decade has produced better clinical outcomes in patients infected with viral genotype 1.However,the published literature shows no improvement in clinical outcomes in patients infected with viral genotypes 2 or 3 when they are treated with pegylated interferon as opposed to nonpegylated interferon,both given in combination with ribavarin.This is significant because the cost of a 24-wk treatment with pegylated interferon in lessdeveloped countries is between six and 30 times greater than that of treatment with interferon.Thus,clinicians need to carefully consider the cost-versusbenefit of using pegylated interferon to treat CHC,particularly when there is no evidence for clinically measurable benefits in patients with genotypes 2 and 3 infections.

  19. Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients: The effect of pegylated interferon plus ribavirin treatment

    Institute of Scientific and Technical Information of China (English)

    Ioannis S Elefsiniotis; Elena Vezali; Konstantinos Kamposioras; Konstantinos D Pantazis; Radostina Tontorova; Ioannis Ketikoglou; Antonios Moulakakis; George Saroglou

    2006-01-01

    AIM: To retrospectively evaluate the vaccinationinduced anti-HBs seroconversion rates in treatmentnaive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment.METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 μg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine.Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups:Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment.Determination of anti-HBs was performed at mo 1, 2,and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05).RESULTS: Fifty-eight of 70 group A patients (82.85%),20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1(20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%,P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up.CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR

  20. Alkaline phosphatase predicts relapse in chronic hepatitis C patients with end-of-treatment response

    Institute of Scientific and Technical Information of China (English)

    Gerd; Bodlaj; Rainer; Hubmann; Karim; Saleh; Tatjana; Stojakovic; Georg; Biesenbach; Jrg; Berg

    2010-01-01

    AIM: To investigate relapse predictors in chronic hepatitis C (CHC) patients with end-of-treatment response (ETR), after pegylated interferon-α (PegIFN-α) and ribavirin treatment. METHODS: In a retrospective study we evaluated a spectrum of predictors of relapse after PegIFN-α and ribavirin treatment in 86 CHC patients with ETR. Viral loads were determined with real-time reverse transcrip-tion polymerase chain reaction. Hepatitis C virus geno-typing was performed by sequencing analysis. Patients with genoty...

  1. Comparison of antibody responses against Mycobacterium tuberculosis antigen Rv0679c in tuberculosis patients from the endemic and non-endemic regions of the Beijing genotype: a case control study.

    Science.gov (United States)

    Zhao, Jingge; Matsuba, Takashi; Zhang, Xiaoyan; Leano, Susan; Nakajima, Chie; Chagan-Yasutan, Haorile; Telan, Elizabeth Freda; Suzuki, Yasuhiko; Hattori, Toshio

    2017-05-15

    Strains of the Beijing genotype of Mycobacterium tuberculosis (MTB) are reportedly associated with the virulence of tuberculosis (TB) infection, unfavorable outcomes of anti-TB treatment, and the global TB pandemic. Rv0679c, a hypothetical membrane protein related to host cell invasion, has a Beijing genotype-specific mutation at residue 142 (Asn142Lys). Antigenicity differences between Rv0679c-Asn142 (N-type) and Rv0679c-Lys142 (K-type) have been previously observed in mice antigen-antibody responses. However, the immune response to Rv0679c in humans remains unknown. Therefore, we aimed to investigate the anti-Rv0679c immune response in TB patients from the endemic and non-endemic regions of the Beijing MTB genotype. We analyzed the Rv0679c-specific antibody responses in 84 subjects from the endemic region of the Beijing genotype MTB in China, including 45 pulmonary TB patients (C-PTB) and 39 healthy controls (C-HC), and 81 subjects from the Philippines (the endemic region of the non-Beijing genotype), including 51 pulmonary TB patients (P-PTB) and 30 healthy controls (P-HC). Anti-tuberculous-glycolipid (TBGL) antigen was used as the control antibody. TBGL IgG titers were higher in both C-PTB and P-PTB than those in their corresponding HC (C-PTB median 4.2, P-PTB median 11.2; C-PTB vs. P-PTB, p > 0.05), suggesting immune response comparability in PTB from two different countries. C-PTB showed a higher response compared to C-HC for anti-K-type IgG (53.3%) than anti-N-type IgG (6.67%); this response was not observed in P-PTB (both N-type and K-type 9.80%). Dimorphic antigen Rv0679c was found to be associated with distinct immune response patterns, indicating the role of Beijing/non-Beijing genotype of MTB in stimulating specific responses in TB patients from the endemic region of Beijing MTB. Meanwhile, reactions to Rv0679c in patients and HC from non-endemic regions of the Beijing MTB may be caused by the response to the common epitope of Rv0679c N/K-type.

  2. An Improved CHC Algorithm for Damage Diagnosis of Offshore Platforms

    Institute of Scientific and Technical Information of China (English)

    HUANG Weiping; WANG Xiaoyan

    2007-01-01

    An improved CHC algorithm is proposed in the paper and it could be used for the damage diagnosis of structures. It breaks the bottle neck of genetic algorithm in the damage diagnosis of large structures and takes a shorter time than the SGA (Standard Genetic Algorithm) in diagnosing structural damage with the same level of error. The case studies show that the algorithm is rapid in convergence and produces satisfactory results in diagnosing both fixed-end beams and jacket offshore platforms.

  3. Distribution study of Chlamydia trachomatis genotypes in symptomatic patients in Buenos Aires, Argentina: association between genotype E and neonatal conjunctivitis

    Directory of Open Access Journals (Sweden)

    Corominas Ana I

    2010-02-01

    Full Text Available Abstract Background Chlamydia trachomatis infections are the most prevalent sexually transmitted bacterial infections in the world. There is scarce data available referring to the distribution of C. trachomatis genotypes in Argentina. The aim of this study was to identify the genotypes of C. trachomatis circulating in the metropolitan area of Buenos Aires (Argentina associated with ophthalmia neonatorum and genital infections. Findings From 2001 to 2006, 199 positive samples for C. trachomatis infection from symptomatic adult patients and neonates with ophthalmia neonatorum from two public hospitals were studied. C. trachomatis genotypes were determined by PCR-RFLP of an ompA fragment. Genotype E was the most prevalent regardless of the sample origin (46.3% 57/123 in adults and 72.4% 55/76 in neonates, followed by genotype D (19.5% 24/123 and F (14.6% 18/123 in adults, and G (9.2% 7/76 and D (7.9% 6/76 in neonates. We detected a significantly higher frequency of genotype E (p ophthalmia neonatorum than in genital specimens. Genotype D was associated with genital localization (p Conclusion We found a particularly increased frequency of C. trachomatis genotype E in neonatal conjunctivitis, which may indicate an epidemiological association between this genotype and the newborn population. The present study also contributed to increase the knowledge on genotype distribution of Chlamydia trachomatis in symptomatic adult patients in Buenos Aires, Argentina, in which genotypes E, D and F were the predominant ones.

  4. Genotypes of Helicobacter pylori in patients with peptic ulcer bleeding

    Institute of Scientific and Technical Information of China (English)

    Chin-Lin Perng; Hwai-Jeng Lin; Wen-Ching Lo; Guan-Ying Tseng; I-Chen Sun; Yueh-Hsing Ou

    2004-01-01

    AIM: Helicobacter pyloricauses chronic gastritis, peptic ulcer,gastric cancer and MALT-lymphoma. Different genotypes of Helicobacter pylori are confirmed from diverse geographic areas. Its association with bleeding peptic ulcer remains controversial. The aim of this study was to investigate the Helicobacter pylori vac4 alleles, cagA and iceA in patients with bleeding peptic ulcer.METHODS: We enrolled patients with bleeding, nonbleeding peptic ulcers and chronic gastritis. Biopsy specimens were obtained from the antrum of the stomach for rapid urease test, bacterial culture and PCR assay. DNA extraction and polymerase chain reaction were used to detect the presence or absence of cagA and to assess the polymorphism of vac4 and iceA.RESULTS: A total of 168 patients (60.4%) (25 patients with chronic gastritis, 26 patients with bleeding gastric ulcer,51 patients with non-bleeding gastric ulcer, 26 patients with bleeding duodenal ulcer, and 40 patients with non-bleeding duodenal ulcer) were found to have positive PCR results between January 2001 and December 2002. Concerning genotypes, we found cagA (139/278, 50%), vacA s1a (127/278, 45.7%), and iceA1 (125/278, 45%) predominated in all studied patients. In patients with bleeding peptic ulcers,vac4 s1a and m1T were fewer than those in patients with non-bleeding peptic ulcers (37/106 vs69/135, P=0.017, and 4/106 vs21/135, P=0.002).CONCLUSION: In patients with peptic ulcers, Hpylori vacA s1a and m1T prevent bleeding complication.

  5. Apolipoprotein E genotype in patients with Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    罗本燕; 陈智; 张艳艳; 潘小平; 李霞; 陈峰

    2003-01-01

    Objective To explore the frequency and significance of ApoE gene polymorphisms in patients with sporadic Alzheimer's disease (AD).Methods Single nucleotide polymorphisms of the ApoE gene were analyzed in 32 cases of AD and 26 controls, using PCR and gene sequencing.Results The single nucleotide polymorphism of ApoE gene 462C/G was significantly associated with AD (P<0.05).Conclusions The 462C/G polymorphism might be a specific genotype in Chinese patients with sporadic AD.

  6. Prevalence of hepatitis C genotypes in patients with hepatitis C in Lorestan province (2009-2013

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    Mohammad Reza Nazer

    2014-05-01

    Full Text Available Background: Determining hepatitis C genotypes is important to detect the various aspects of this infection, including its epidemiology, pathogenesis and response to anti-viral treatments. The aim of this study was to investigate the prevalence of hepatitis C genotypes in patients admitted to the Infectious Diseases Clinic in Khorramabad. Methods: Out of all the patients admitted to the Infectious Disease Clinic in Khorramabad in a four-year period (April 2009 to March 2013, 120 patients who met the inclusion criteria of the study were evaluated. The PCR method was used to examine the serums of the patients with hepatitis C in terms of the type of genotype. Results: Out of 120 patients, 101 (84.2% were male and 19 (15.8% were female. The most prevalent genotypes were 3a (65%, 1a (24.2%, 1a/1b (5%, and 2 (1.7%, respectively. The genotypes of 5 patients (4.2% could not be determined. No significant relationships were found between gender and genotype, and age group and genotype. Moreover, 18.3% of the patients were HIV-positive. Conclusion: In this study, genotype 3a, the most prevalent genotype, was not consistent with the prevalent genotypes in Arab, European, American, and African countries. Furthermore, genotype 1a was the second most prevalent genotype, while it has been reported as the most prevalent genotype by numerous studies conducted in Iran.

  7. Cost-effectiveness of narlaprevir in the chronic hepatitis C (genotype 1 therapy in treatment-naïve patients and relapsers

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    D. A. Gusev

    2016-01-01

    Full Text Available In the treatment of chronic hepatitis C (CHC protease inhibitors (PI are actively used. The aim of this analysis was to evaluate the cost-effectiveness of narlaprevir and simeprevir in the CHC (genotype 1 therapy in treatment-naïve patients and relapsers.Material and methods. Analysis of the cost-effectiveness of simeprevir and narlaprevir was conducted from the perspective of the health care system based on QUEST-1, QUEST-2, ASPIRE and PIONEER clinical trials. The relative risk of achieving SVR 24 compared to the peg-INF + RBV therapy was used in the model. Treatment discontinuation in patients receiving narlaprevir assumed in the absence of a SVR after 12 weeks and in patients receiving simeprevir in the SVR absence after 4 weeks. The cost of narlaprevir was calculated on the basis of estimated registration price in case of EDL inclusion, including VAT. Costs of other antiviral drugs were in line with the results of 2016 average auctions prices.Results. In the base case costs on antiviral drugs with narlaprevir as therapy are lower compared with simeprevir by 37,3 % (542,0 and 864,6 thousand rur, respectively, and the cost per patient with SVR 24 by 34,5%. In patients after relapse costs on antiviral drugs with narlaprevir as first-line therapy will decrease compared with simeprevir by 22,8% (542,0 and 702,5 thousand rur, respectively, and the cost per patient with SVR 24 by 41,3%. The sensitivity analysis demonstrated a high reliability of obtained results.Conclusions. With comparable clinical efficacy and tolerability of narlaprevir and simeprevir both in treatment-naïve patients and patients with relapse after therapy, which included pegylated interferon and ribavirin, narlaprevir reduces the burden on the budget.

  8. An IL28B genotype-based clinical prediction model for treatment of chronic hepatitis C.

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    Thomas R O'Brien

    Full Text Available BACKGROUND: Genetic variation in IL28B and other factors are associated with sustained virological response (SVR after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC. Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables. METHODS: HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC. RESULTS: Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p10% (43.3% of subjects had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study. CONCLUSION: A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC.

  9. Prevalence of antinuclear and anti-liver-kidney-microsome type-1 antibodies in patients with chronic hepatitis C in China

    Institute of Scientific and Technical Information of China (English)

    BAI Li; FENG Zhen-ru; LU Hai-ying; LI Wen-gang; YU Min; XU Xiao-yuan

    2009-01-01

    Background Hepatitis C virus (HCV) infection may induce autoimmune response and autoantibodies can be detected in chronic hepatitis C (CHC) patients. However, the reported positive rate of autoantibodies in CHC patients in China varies considerably. In this study, we investigated the prevalence of antinuclear antibodies (ANA) and anti-liver-kidney-microsome type 1 autoantibodies (anti-LKM-1) in a large cohort of CHC patients, and analyzed the factors related to the presence of the autoantibodies. Methods A total of 360 CHC patients were enrolled in this study. Serum ANA and anti-LKM-1 were detected by indirect immunofluorescence and enzyme-linked immunosorbent assay, respectively. Clinical analysis was performed to disclose the related factors to autoantibody production. Results The prevalence of ANA and anti-LKM-1 in CHC patients was 12.5% (45/360) and 2.5% (9/360), respectively. Women had a higher prevalence than men (18.9% vs 11.4%, P=0.046). Patients with positive autoantibodies had lower HCV RNA levels (1.2x107 copies/L vs 7.2x107 copies/L, P <0.05). Positive ANA was associated with higher serum globulin (P<0.05). Stratified analysis showed that there were no significant differences in age, HCV genotype, disease course, clinical stage, prevalence of cirrhosis and interferon therapy between autoantibody-positive and-negative subgroups. Conclusion Autoantibodies can be induced in the course of CHC, and some CHC patients can even develop autoimmune hepatitis.

  10. MTP -493G/T gene polymorphism is associated with steatosis in hepatitis C-infected patients

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, E.R.F. [Departamento de Gastroenterologia, LIM-07, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Departamento de Bioquímica, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Oliveira, C.P.M.S. [Departamento de Gastroenterologia, LIM-07, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Correa-Giannella, M.L. [Laboratório de Endocrinologia Celular e Molecular, LIM-25, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Stefano, J.T. [Departamento de Gastroenterologia, LIM-07, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Cavaleiro, A.M.; Fortes, M.A.H.Z. [Laboratório de Endocrinologia Celular e Molecular, LIM-25, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Muniz, M.T.C.; Silva, F.S. [Departamento de Bioquímica, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Pereira, L.M.M.B. [Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de Pernambuco, Recife, PE (Brazil); Instituto do Fígado de Pernambuco, Recife, PE (Brazil); Carrilho, F.J. [Departamento de Gastroenterologia, LIM-07, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2011-12-09

    The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.

  11. Prevalence of mixed hepatitis C virus (HCV genotypes among recently diagnosed dialysis patients with HCV infection

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    Mohammed A Al Balwi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV infection is considered a major health problem recognized globally. HCV is a major cause of chronic liver disease that may lead to cirrhosis and hepatocellular carcinoma. The aim of this study was to investigate the prevalence of multiple (mixed HCV genotypes in Saudi patients recently diagnosed with HCV infection and their association with various clinical risk factors. We examined a total of 1,292 newly diagnosed HCV-positive cases between January 2006 and July 2009 at the Molecular Pathology Laboratory, King Abdulaziz Medical City, Riyadh. The clinical and laboratory data of the study patients were collected. The HCV-RNA viral load and its genotyping were carried out with RT-PCR technology to assist in the follow-up and management of HCV-infected patients undergoing antiviral therapy. Twenty-two patients (1.7% were found to have mixed HCV genotypes; of them, mixed genotypes associated with genotype-4 were seen in 19 patients (86%, mixed genotypes associated with genotype-1 were found in 68.4%, with genotype-3 in 26.3% and with genotype-2 in 5.3%. Additionally, mixed genotypes associated with genotype-1 were seen in three cases (13.6%; they were associated with genotype-2 in two (66.7% and with genotype-5 in one patient (33.3%. In conclusion, the prevalence rate of mixed HCV genotypes in the cohort of the newly infected Saudi patients was 1.7%, with genotype-4 being the most frequent genotype encountered.

  12. Hepatitis B virus genotypes in chronic liver disease patients from New Delhi, India

    Institute of Scientific and Technical Information of China (English)

    Saket Chattopadhyay; Bhudev Chandra Das; Premashis Kar

    2006-01-01

    AIM: To study the Hepatitis B virus (HBV) genotypes and their effect on the progression and outcome in patients with chronic liver diseases from New Delhi, India.METHODS: Sera from 100 HBV-related chronic liver disease (CLDB) cases were tested for HBV genotype using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Type-specific primers-based PCR (TSP-PCR) targeting to the surface (S)gene encoding hepatitis B surface antigen.RESULTS: Only genotypes A and D were present and genotype D was dominant. Genotype D was present in all CLDB patient categories. The genotype distribution for the 100 patients with CLDB was as follows: genotype A, 16/100 (16%) (7/40- 17% chronic hepatitis B (CHB);8/47, 17%, HBV-related cirrhosis (CRB); 1/13, 7.6%,HBV-related hepatocellular carcinoma (HCCB); genotype D- 84/100 (84%) (32/40- 80% CHB; 38/47- 81%, CRB;11/13, 85%, HCCB); genotype A + D, 3/100 (3%) (1/40-3% CHB; 1/47- 2%, CRB; 1/13, 7.6%, HCCB); C, 0; B, 0;E, 0; F, 0; G 0, H 0; (P < 0.01, genotype D vs A).CONCLUSION: Only HBV genotypes A and D were present in patients with CLDB from New Delhi, India.Compared with genotype D, genotype A patients had no significant clinical or biochemical differences (P > 0.05).Mixed infection with genotype A and D were seen in 3%of the cases. Genotype D was the dominant genotype prevalent in all patient categories.

  13. Microcytic hypochromic anemia patients with thalassemia : Genotyping approach

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    Rahim Fakher

    2009-03-01

    Full Text Available Background: Microcytic hypochromic anemia is a common condition in clinical practice, and alpha-thalassemia has to be considered as a differential diagnosis. Aims: This study was conducted to evaluate the frequency of α-gene, β-gene and hemoglobin variant numbers in subjects with microcytic hypochromic anemia. Setting And Designs: Population-based case-control study in the Iranian population. Materials And Methods: A total of 340 subjects from southwest part of Iran were studied in the Research Center of Thalassemia and Hemoglobinopathies (RCTH, Iran. Genotyping for known a- and b-gene mutations was done with gap-PCR and ARMS. In cases of some rare mutations, the genotyping was done with the help of other techniques such as RFLP and ARMS-PCR. Statistical Analysis: Statistical analysis was carried out by SPSS 11.5 and an independent-sample t test. Results: Out of the total 340 individuals, 325 individuals were evaluated to have microcytic hypochromic anemia based on initial hematological parameters such as MCV< 80 fl; MCH < 27 pg; the remaining 15 patients were diagnosed with no definite etiology. The overall frequency of -α3.7 deletion in 325 individuals was 20.3%. The most frequent mutations were IVS II-I, CD 36/37 and IVS I-110 with frequencies of 6.31%, 5.27% and 1.64%, respectively. Only, there was a significant difference between beta-thalassemia trait and beta-thalassemia major with regard to MCV (P < 0.05 and MCH (P < 0.05 indices, and also MCH index between beta-thalassemia trait and Hb variants (P < 0.05. Conclusion: Molecular genotyping provides a rapid and reliable method for identification of common, rare and unknown a- and b-gene mutations, which help to diagnose unexplained microcytosis and thus prevent unnecessary iron supplementation.

  14. The prevalence of mixed genotype infections in Polish patients with hepatitis C

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    Ewelina Gowin

    2016-02-01

    Conclusions: The results obtained showed that infection with mixed HCV genotypes in Polish patients with hepatitis C is uncommon. The selective elimination of genotypes 3a and 4a after therapy confirms the greater resistance to treatment of genotype 1b. In the context of new anti-HCV drug development, further investigations are needed to determine the clinical importance of mixed HCV infection.

  15. Distribution of viral genotypes and extrahepatic manifestations in patients with chronic hepatitis C in Eastern Turkey

    OpenAIRE

    YILMAZ, Sibel İBA; Erol, Serpil; ÖZBEK, Ahmet; Parlak, Mehmet

    2015-01-01

    To investigate the distribution of viral genotypes, the extrahepatic manifestations, and the relationship between genotypes and extrahepatic manifestations in patients with chronic hepatitis C. Materials and methods: The study included 62 treatment-naive patients with chronic hepatitis C infection. Genotype determination was performed by DNA sequencing analysis. To investigate extrahepatic manifestations, the patients' data, recorded prospectively during the pretreatment period, were an...

  16. Study of Various HCV Genotypes in Patients Managing by Referral Clinic in Yazd Province

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    M Pedarzadeh

    2012-02-01

    Full Text Available Introduction: Determining virus genotype is a major factor for initiation of treatment because various kinds of genotypes need different antiviral drugs. Distribution of hepatitis C genotype in the word is variable in each country or even in each province. So we need to determine distribution pattern of hepatitis C genotype in our region. This study was performed in referral clinic of Yazd province. Methods: This was a descriptive study conducted between 2007 and 2010 on patients who were observed by Yazd referral clinic (the clinic for evaluating and management of patients with high risk behaviors. Ninety two patients who had positive RIBA test for hepatitis C infection were randomly selected and entered the study. Genotyping was performed using RT-PCR method. The primer was "universal primer HCV". Prevalence of various genotypes was analyzed according to gender, addiction and co- existence of HCV-HIV infection. Personal information and laboratory results were analyzed using SPSS. Results: The most common genotype in our study was genotype 3a (65% of cases, followed by 1a (35%. Globally 83% of patients were IV drug addict. Genotype distribution in these patients was similar to others. Fifteen patients had co-infection of HCV-HIV, and 47% of them were contaminated by genotype 1a and 53% with 3a. We could not find any patient contaminated with genotypes 2 or 4. No other genotypes except 1 & 3 or mixed genotype infection could be determined in our patients. Twenty three percent of patients had negative PCR despite positive RIBA test. This indicates that self improvement from acute hepatitis C infection in IV drug addict patients is similar to other people. Conclusion: According to the results of our study, about 2/3 of patients were infected by genotype 3a. This kind of chronic hepatitis C shows a better response to treatment comparing genotype 1a (or 1b with shorter duration and lower cost drugs. But despite higher incidence of genotype 3a, we

  17. Hepatitis B genotypes: Relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia

    Institute of Scientific and Technical Information of China (English)

    Ayman A Abdo; Badr M Al-Jarallah; Faisal M Sanai; Ahmad S Hersi; Khalid Al-Swat; Nahla A Azzam; Manal Al-Dukhayil; Amira Al-Maarik; Faleh Z Al-Faleh

    2006-01-01

    AIM: To identify the most common hepatitis B virus (HBV)genotype in Saudi Arabia, and correlate the prevailing genotypes with the clinical outcome of patients.METHODS: Patients were consecutively recruited from the hepatology clinics of two tertiary care referral centers. Patients were categorized into 4 different groups:group 1, patients with hepatitis B and normal liver enzymes; group 2, patients with hepatitis B and abnormal liver enzymes but without cirrhosis; group 3, patients with hepatitis B and liver cirrhosis; group 4, patients with hepatitis B and hepatocellular carcinoma. All patients had a positive hepatitis B surface antigen (HBsAg). Genotyping of HBV was performed by nested PCR-mediated amplification of the target sequence and hybridization with sequence-specific oligonucleotides.RESULTS: Seventy patients were enrolled in this study.They were predominantly male (72.9%) in their midforty's (mean age 47 years). Forty-nine (70%) patients were hepatitis B envelope antigen (HBeAg) negative.The majority of patients (64%) acquired HBV through unknown risk factors. Hepatitis B genotyping revealed that 57 patients (81.4%) were genotype D, 1 patient (1.4%) had genotype A, 1 patient (1.4%) had genotype C, and 4 patients (5.7%) had genotype E, while 7 patients (10%) had mixed genotype (4 patients ADG, 1 patient DE, 1 patient DF, and 1 patient ADFG). Based on univariate analysis of genotype D patients, significant predictors of advanced liver disease were age, gender,aspartate transaminase, alanine transaminase, albumin,bilirubin, and alkaline phosphatase (all P < 0.001). In multivariate analysis decreased hemoglobin (r = -0.05;95% CI: -0.08 to -0.03; P = 0.001) and albumin levels (r = -0.004; 95% CI: -0.007 to -0.001; P = 0.002) were highly significant predictors of advanced liver disease.In patients with HBV genotype D, HBeAg negativity was found to increase across advancing stages of liver disease (P = 0.024).CONCLUSION: This study highlights that the vast

  18. Genotyping and molecular analysis of Enterocytozoon bieneusi isolated from immunocompromised patients in Iran.

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    Mirjalali, Hamed; Mirhendi, Hossein; Meamar, Ahmad Reza; Mohebali, Mehdi; Askari, Zeynab; Mirsamadi, Elnaz Sadat; Rezaeian, Mostafa

    2015-12-01

    Microsporidia are known as opportunistic unicellular pathogens, particularly so in individuals with congenital or acquired immunodeficiency. Enterocytozoon bieneusi is one of the most common species infecting both immunocompromised and immunocompetent individuals. The aim of this study was to assess the distribution of E. bieneusi genotypes among immunocompromised patients in Iran. From 329 stool samples referred for parasitological analysis during 2011-2014, 14 samples from immunocompromised patients proving positive for E. bieneusi by SSU rDNA analysis were selected. Genotyping was carried out using specific primers targeting the Internal Transcribed Spacer (ITS) region. Subsequently, all samples were sequenced and results queried against the GenBank database. Moreover, sequences were subject to phylogenetic analysis. The expected amplification product was generated for all samples. Genotype D was identified in patients with HIV+/AIDS, transplant recipients, and cancer patients, while Genotype E was identified only in cancer and HIV+/AIDS patients. Phylogenetic analysis revealed that there was no relationship between genotypes and types of immunosuppression, whereas most genotype D isolates grouped with those described previously from cattle, horses, birds, and humans. E. bieneusi genotype D appears to be the most frequent genotype in immunocompromised patients, while Genotype E was observed only in HIV+/AIDS patients and cancer patients, not transplant recipients.

  19. Genotyping of human rhinovirus in adult patients with acute respiratory infections identified predominant infections of genotype A21

    Science.gov (United States)

    Ren, Lili; Yang, Donghong; Ren, Xianwen; Li, Mingkun; Mu, Xinlin; Wang, Qi; Cao, Jie; Hu, Ke; Yan, Chunliang; Fan, Hongwei; Li, Xiangxin; Chen, Yusheng; Wang, Ruiqin; An, Fucheng; An, Shuchang; Luo, Ming; Wang, Ying; Xiao, Yan; Xiang, Zichun; Xiao, Yan; Li, Li; Huang, Fang; Jin, Qi; Gao, Zhancheng; Wang, Jianwei

    2017-01-01

    Human rhinovirus (HRV) is an important causative agent of acute respiratory tract infections (ARTIs). The roles of specific HRV genotypes in patients suffering from ARTIs have not been well established. We recruited 147 adult inpatients with community-acquired pneumonia (CAP) and 291 adult outpatients with upper ARTIs (URTIs). Respiratory pathogens were screened via PCR assays. HRV was detected in 42 patients, with 35 species A, five B and two C. Seventeen genotypes were identified, and HRV-A21 ranked the highest (9/42, 21.4%). The HRV-A21-positive infections were detected in four patients with CAP and in five with URTIs, all without co-infections. The HRV-A21 genome sequenced in this study contained 12 novel coding polymorphisms in viral protein (VP) 1, VP2 EF loop, VP3 knob and 3D regions. The infections of HRV-A21 virus obtained in this study could not be neutralized by antiserum of HRV-A21 prototype strain (VR-1131), indicating remarkable antigenic variation. Metagenomic analysis showed the HRV-A21 reads were dominant in bronchoalveolar lavage fluid of the three HRV-A21-positive patients with severe CAP, in which two dead. Our results highlight an unexpected infection of genotype HRV-A21 in the clinic, indicating the necessity of precise genotyping and surveillance of HRVs to improve the clinical management of ARTIs. PMID:28128353

  20. Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses

    DEFF Research Database (Denmark)

    Pedersen, Jannie; Jensen, Tanja B; Carlsen, Thomas H R;

    2013-01-01

    patients with chronic HCV infection with and without sustained virologic response when tested against any of the included culture viruses. However, NAb50-titers varied significantly with a mean reciprocal NAb50-titer of 800 (range: 100-6400) against DH6/JFH1 compared to a mean NAb50-titer of 50 (range:......The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV) infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1......, infection treated with pegylated interferon-α and ribavirin. Thirty-nine patients with chronic hepatitis C, genotype 1a or 1b, with either sustained virologic response (n = 23) or non-sustained virologic response (n = 16) were enrolled. Samples taken prior to treatment were tested for their ability...

  1. Virologic and clinical characteristics of HBV genotypes/subgenotypes in 487 Chinese pediatric patients with CHB

    OpenAIRE

    Gu Mei-Lei; Li Xiao-Dong; Xing Xiao-Yan; Dong Yi; Duan Zhong-Ping; Song Hong-Bin; Li Jin; Zhong Yan-Wei; Han Yu-Kun; Zhu Shi-Shu; Zhang Hong-Fei

    2011-01-01

    Abstract Background The association of hepatitis B virus (HBV) genotypes/subgenotypes with clinical characteristics is increasingly recognized. However, the virologic and clinical features of HBV genotypes/subgenotypes in pediatric patients remain largely unknown. Methods Four hundred and eighty-seven pediatric inpatients with CHB were investigated, including 217 nucleos(t)ide analog-experienced patients. HBV genotypes/subgenotypes and reverse transcriptase (RT) mutations were determined by d...

  2. Distribution of Hepatitis B Virus Genotypes among Patients with Chronic Infection in Japan Shifting toward an Increase of Genotype A▿

    Science.gov (United States)

    Matsuura, Kentaro; Tanaka, Yasuhito; Hige, Shuhei; Yamada, Gotaro; Murawaki, Yoshikazu; Komatsu, Masafumi; Kuramitsu, Tomoyuki; Kawata, Sumio; Tanaka, Eiji; Izumi, Namiki; Okuse, Chiaki; Kakumu, Shinichi; Okanoue, Takeshi; Hino, Keisuke; Hiasa, Yoichi; Sata, Michio; Maeshiro, Tatsuji; Sugauchi, Fuminaka; Nojiri, Shunsuke; Joh, Takashi; Miyakawa, Yuzo; Mizokami, Masashi

    2009-01-01

    Acute hepatitis B virus (HBV) infection has been increasing through promiscuous sexual contacts, and HBV genotype A (HBV/A) is frequent in patients with acute hepatitis B (AHB) in Japan. To compare the geographic distribution of HBV genotypes in patients with chronic hepatitis B (CHB) in Japan between 2005 and 2006 and between 2000 and 2001, with special attention to changes in the proportion of HBV/A, a cohort study was performed to survey changes in genotypes of CHB patients at 16 hospitals throughout Japan. Furthermore, we investigated the clinical characteristics of each genotype and examined the genomic characteristics of HBV/A isolates by molecular evolutionary analyses. Of the 1,271 patients, 3.5%, 14.1%, and 82.3% were infected with HBV/A, -B, and -C, respectively. In comparison with our previous survey during 2000 and 2001, HBV/A was twice as frequent (3.5% versus 1.7%; P = 0.02). The mean age was lower in the patients with HBV/A than in those with HBV/B or -C. Based on phylogenetic analyses of 11 full-length genomes and 29 pre-S2/S region sequences from patients, HBV/A isolates were imported from Europe and the United States, as well as the Philippines and India. They clustered with HBV/A from AHB patients and have spread throughout Japan. HBV/A has been increasing in CHB patients in Japan as a consequence of AHB spreading in the younger generation through promiscuous sexual contacts, aided by a tendency of HBV/A to induce chronic hepatitis. The spread of HBV/A infection in Japan should be prevented by universal vaccination programs. PMID:19297602

  3. Spontaneous clearance of chronic hepatitis C is rare in HIV-infected patients after effective use of combination antiretroviral therapy.

    Science.gov (United States)

    Frias, Mario; Rivero-Juarez, Antonio; Tellez, Francisco; Perez-Perez, Monserrat; Camacho, Angela; Machuca, Isabel; Lorenzo-Moncada, Sandra; Lopez-Lopez, Pedro; Rivero, Antonio

    2017-01-01

    To evaluate the rate of spontaneous resolution of chronic hepatitis C (CHC) infection in a cohort of HIV-infected patients. A retrospective analysis of 509 HIV-infected patients with chronic HCV infection was performed at two reference hospitals in Andalusia. The main variable of the study was spontaneous clearance of CHC, defined as a negative HCV RNA result after at least two previous quantitative measurements of HCV RNA separated by a minimum of 12 months. Of 509 patients, 3 (0.59%; 95% CI: 0.15%-1.6%) experienced spontaneous clearance of CHC. After combination antiretroviral therapy (cART) initiation, two of three cases experienced an increased CD4+ count, coinciding with HCV viral clearance. All patients were IL28B CC carriers, 2 were co-infected with HCV genotype 3 (the HCV genotype of the remaining patient was not available). Spontaneous clearance of CHC is a rare event in the context of HIV/HCV co-infected patients and may be associated with the effective use of cART and thus HIV suppression.

  4. Serum interferon-related microRNAs as biomarkers to predict the response to interferon therapy in chronic hepatitis C genotype 4.

    Science.gov (United States)

    Motawi, Tarek Kamal; Shaker, Olfat Gamil; El-Maraghy, Shohda Assem; Senousy, Mahmoud Ahmed

    2015-01-01

    MicroRNAs are messengers during interferon-virus interplay and are involved in antiviral immunity, however, little is known about interferon-related microRNAs regarding their detection in serum and their potential use as non-invasive diagnostic and prognostic biomarkers in chronic hepatitis C (CHC). To elucidate some of the molecular aspects underlying failure of pegylated interferon-α/ribavirin therapy, we investigated pretreatment expression profiles of seven selected interferon-related microRNAs (miR-146a, miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296) by quantitative RT-PCR custom array technology in serum of Egyptian CHC genotype 4 patients and whether their pretreatment levels would predict patient response to the combination therapy. One hundred and six CHC patients and forty matched healthy controls were included. Patients were divided into sustained virological response (SVR) and non-responder (NR) groups. Serum miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296 were upregulated, whereas serum miR-146a was downregulated in CHC compared to controls. Significant correlations were found between expression levels of studied microRNAs and also with clinical data. Pretreatment levels of miR-34a, miR-130a, and miR-195 were significantly higher, whereas miR-192 and miR-296 levels were significantly lower in SVR than NR patients. miR-19a and miR-146a levels were not significantly different between the two groups. miR-34a was superior to differentiate CHC from controls, whereas miR-296 was superior to discriminate SVR from NR patients by receiver operating characteristic analysis. Multivariate logistic analysis revealed miR-34a and miR-195 as independent predictors for SVR and miR-192 as an independent variable for non-response. In conclusion, pretreatment expression profiles of five interferon-related microRNAs are associated with treatment outcome in CHC. Of these, miR-34a, miR-195, and miR-192 could predict treatment response. The profiling

  5. Prevailing HCV genotypes and subtypes among hiv infected patients in Georgia.

    Science.gov (United States)

    Karchava, M; Sharvadze, L; Gatserelia, L; Badridze, N; Tsertsvadze, T

    2009-12-01

    Recent analysis of antiretroviral treatment (ART) program data in Georgia showed that end-stage liver disease was a leading cause of death among HIV/HCV co infected patients in 2005. The objective of this retrospective study was to study prevailing genotypes and subtypes of HCV virus in a cohort of HIV infected patients. The investigation revealed that of 1490 patients, 879 (59%) were hepatitis C antibody positive. Detectable HCV RNA was found among 91% of patients. Median liver HCV RNA level was higher than among mono-infected patients. The most prevalent genotypes were genotype 1 (41.6%), followed by genotype 3 (34.7%) and genotype 2 (17.6%), inter (mix) genotype recombinants were found among 5.8 % of patients. The genotype distribution in our study is slightly different from what was seen in Georgia in 2000. The differences of prevailing HCV genotypes among general population and HIV co infected group was probably attributed to the different methods for sample selection used within our study or possible influence of diverse transmission networks among HIV infected group. Another explanation can be the possible shift from predominance of genotype 1 to non 1 genotypes. The higher number intergenotype recombinant forms might be the result of continues parenteral exposure to different HCV genotypes during drug injection paraphernalia. Our study demonstrated high prevalence of HCV infection among HIV-infected patients and revealed 1b as predominant genotype. IDUs were less likely to spontaneously clear the virus than homosexual man and heterosexually infected woman. A greater HCV RNA levels were associated with a greater chance to be infected with HCV genotypes 1. Possible shift from predominance of genotype 1 to non 1 genotypes can be of option. This shift may have a major and beneficial impact on treatment schedules and costs. The higher number intergenotype recombinant forms might be the results of continues parenteral exposure to different HCV genotypes during

  6. Microsatellite-based genotyping of Candida albicans isolated from patients with superficial candidiasis.

    Science.gov (United States)

    Shimizu, Kazue; Hattori, Hisao; Adachi, Hidesada; Oshima, Ryosuke; Horii, Toshinobu; Tanaka, Reiko; Yaguchi, Takashi; Tomita, Yasushi; Akiyama, Masashi; Kawamoto, Fumihiko; Kanbe, Toshio

    2011-01-01

    This study aimed to examine the genotype distribution of Candida albicans and the major genotypes involved in superficial candidiasis. The genotypes of C. albicans isolated from the infection sites of patients with superficial candidiasis (referred to as infection isolates) were analyzed by fragment analysis using 4 microsatellite markers (HIS3, CDC3, CAI and CAIII). Genotypes of the infection isolates were compared with those of C. albicans isolated from oral mucosa of non-candidiasis patients (referred to as oral isolates). Isolates of C. albicans showed 4 major genotypes for HIS3/CAI (" a " for 148 : 148 / 23 : 23," b " for 148 : 160 / 33 : 41," c " for 148 : 164 / 32 : 41 and " d " for 152 : 152 / 18 : 27). The genotypes " a "," b " and " d " were commonly found in oral (4.7, 8.8 and 7.6%, respectively) and infection (6.6, 9.2 and 15.4%, respectively) isolates. No isolates of genotype " c " were isolated from infection sites. The genotype " a " was found in the isolates from patients with genitalia candidiasis. Genotyping of multiple isolates from an individual patient showed that C. albicans from infection sites was genetically homogenous as compared with that of oral isolates, even in the same patient with candidiasis.

  7. Genotypes of Candida albicans isolated from healthy individuals and their distribution in patients with oral candidiasis.

    Science.gov (United States)

    Takagi, Yuki; Fukano, Hideo; Shimozato, Kazuo; Tanaka, Reiko; Horii, Toshinobu; Kawamoto, Fumihiko; Kanbe, Toshio

    2013-12-01

    For the study of Candida albicans genotypes involved in development of candidiasis, Candida albicans isolates were collected from healthy volunteers and patients with oral candidiasis and genotyped on the basis of 25S rDNA and microsatellite polymorphisms. In the microsatellite analysis using two microsatellite markers (CDC3 and CAI), 63 healthy volunteer isolates were classified into 35 genotypes (allelic relations to CDC3 alleles 1:2/CAI alleles 1:2), among which genotypes II (115:119/23:23), III (115:123/18:27), and V (123:127/32:41) were found at frequencies of 12.7%, 7.9%, and 7.9%, respectively. In 68 oral candidiasis isolates classified into 39 genotypes, genotypes II and III were identified in 4.4% and 20.6% of the isolates, respectively. The frequency of genotype III was higher in the candidiasis isolates than in the healthy isolates (p oral candidiasis.

  8. [Characterization of hepatitis C virus in chronic hepatitis patients: genotypes in the State of Amazonas, Brazil].

    Science.gov (United States)

    Araújo, Ana Ruth; Almeida, Carlos Mauríco de; Fraporti, Liziara; Garcia, Nadja; Lima, Tatiane Amábili de; Maia, Laura Patrícia Viana; Torres, Kátia Luz; Tarragô, Andréa Monteiro; Victória, Flamir; Victória, Marilu; Tateno, Adriana; Levi, José Eduardo; Talhari, Sinésio; Malheiro, Adriana

    2011-10-01

    In the State of Amazonas, data regarding the prevalence of different genotypes of hepatitis C virus remains scarce. The genotype of 69 HCV positive patients was determined. An in-house standardized nested-PCR was used to detect HCV RNA. Genotype assignment was based on type-specific motifs on the sequenced amplicons delimited by primers HC11/HC18 from the 5' untranslated region. Of the 69 patients studied, 65.2% were male and 34.8% were female. Genotype 1 showed the greatest prevalence, followed by 3 and 2. These data suggesting that Manaus is the point of arrival of HCV in the State of Amazonas.

  9. Interrelationship of hepatitis C virus genotypes with patient characteristics in Bahrain

    Science.gov (United States)

    Abdulla, Maheeba A; Murad, Eman A; Aljenaidi, Hend A; Aljowder, Duha R; Aljeeran, Omar IK; Farid, Eman; Al Qamish, Jehad R

    2017-01-01

    Aim Hepatitis C virus (HCV) shows genotype-based variation in prevalence across geographical regions. This study was conducted to understand the clinical interrelationship of HCV genotypes with patient characteristics. Methods Medical records of 122 patients positive for HCV RNA test collected during 2013 and 2014 were included for analysis. Only adults were included in the study. HCV RNA extraction and genotyping was done as part of the routine diagnostic requirements. The association of continuous and categorical variables with genotypes was analyzed through analysis of variance and chi-square tests, respectively. Results Of the 122 patients selected, 103 were Bahrainis, 18 non-Bahrainis, and 1 was unregistered. Genotype 1 was the predominant (53%) one, followed by types 3 (23%) and 4 (20%). Classical symptoms, clinical signs, liver function test, and ultrasonographic results were recorded. Cirrhosis and ascites showed significant variation across genotypes. Although alanine transaminase, total bilirubin, and albumin levels were increased, gamma-glutamyltransferase and alkaline phosphatase levels were normal. About 12% of the subjects were alcohol users, 4% were positive for HIV infection and 2.4% were positive for hepatitis B virus infection. The circulating HCV RNA load was at medium-level in the study cohort and showed significant association with the HCV genotypes and subtypes. Patients with genotype 1a had 6 times more load than patients with type 4 (Prelationship of HCV RNA viral load with the severity of liver disease in our cohort.

  10. Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept Talidomida, peginterferón alfa-2b y ribavirina en el tratamiento de pacientes no respondedores con hepatitis crónica C genotipo 1: estudio piloto

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    Benjamín Pardo-Yules

    2011-12-01

    Full Text Available Background: fewer than half of patients infected with hepatitis C virus (HCV achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV therapy. Aims: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. Methods: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC patients, who had failed to respond to the (Peg-IFN/RBV, with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study. Results: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. Conclusions: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.Antecedentes: menos de la mitad de los pacientes con hepatitis C logra eliminar el virus de manera sostenida después de la terapia con peginterferón alfa y ribavirina (Peg-IFN/RBV. Objetivos: la talidomida posee propiedades antiinflamatorias e inmunomoduladoras a través de la inhibición del TNF-α y al efecto estimulador sobre las células T CD8+. Métodos: se inició un estudio prospectivo y abierto de re-tratamiento de pacientes con hepatitis crónica C genotipo 1, no respondedores al tratamiento con Peg-IFN/RBV, mediante triple terapia añadiendo a los mismos antivirales 200 mg/día de talidomida. Resultados: ninguno de los once pacientes que fueron incluidos en

  11. LIPID METABOLISM DISORDERS IN PATIENTS WITH CHRONIC HEPATITIS C

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    L. I. Tkachenko

    2015-01-01

    Full Text Available Purpose of the study. To study lipid metabolism in chronic hepatitis C and to assess its impact on the formation of insulin resistance, steatosis and progression of liver fibrosis.Materials and methods. The study included 205 patients with chronic hepatitis C (CHC. Conducts research, depending on the genotype C, viral load and body mass index (BMI of the patients.Results. CHC patients revealed a combined hyperlipoproteinemia on the background of op-pression synthesis of apolipoproteins A1 and B. Formation of hepatic steatosis was associated with HCV genotype 3 virus-induced viral load at ≥ 6 log10 IU/ml and metabolic in VL < 6 log10 IU/ml. In patients with chronic hepatitis C genotype 1, high viral load leads to inhibition of protein synthesis conveyor ApoA1 and increased synthesis of cholesterol, accompanied by abdominal obesity and the formation of insulin resistance. CHC patients with BMI < 25 kg/m2 viral load ≥ 6 log10 ME/ml was associated with dyslipidemia IV type on D. Fredriskson (1970, hyperglycemia, insulin resistance and diabetes. The advanced stage of liver fi brosis (F ≥ 3 on a scale METAVIR and non-response to treatment were associated with a decrease in HDL cholesterol below normal. With an increase in viral load > 5 log10 ME/ml signifi cantly increased the risk of lipid and carbohydrate metabolism.

  12. Association of genotypes with viral load and biochemical markers in HCV-infected Sindhi patients

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    Saba Riaz

    Full Text Available Abstract The presented study had two objectives. The first was to examine distributions of Hepatitis C Virus (HCV genotypes in Sindh, Pakistan, where HCV is prevalent. The other was to explore clinically relevant relationships between the genotypes, viral load (measured by real-time polymerase chain reaction assays and biochemical markers. For this, 1471 HCV-infected patients in six cities in Sindh were recruited and sampled. HCV genotype distributions varied among the cities, but genotype 3a was most prevalent, followed by 3b, 1a and 1b (detected in 51.5, 22.7. 9.25 and 3.2% of the cases, respectively. No type-specific sequences were detected in serum samples from 189 (12.8% of the 1471 patients. Frequencies of low (600,000 IU/mL serum viral loads were respectively 45.4, 16.5 and 38.1% for patients infected with genotype 3, and 16.9, 36.9 and 46.2%, respectively, for patients with other genotypes. Infection with genotype 1a was associated with significantly higher (p < 0.005 alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase titers than infection with genotype 3a. The results will help in the formulation of treatment strategies.

  13. Clinical characteristics of Pneumocystis pneumonia in non-HIV patients and prognostic factors including microbiological genotypes

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    Ito Yutaka

    2011-03-01

    Full Text Available Abstract Background The number of patients with non-HIV Pneumocystis pneumonia (PCP is increasing with widespread immunosuppressive treatment. We investigated the clinical characteristics of non-HIV PCP and its association with microbiological genotypes. Methods Between January 2005 and March 2010, all patients in 2 university hospitals who had been diagnosed with PCP by PCR were enrolled in this study. Retrospective chart review of patients, microbiological genotypes, and association with 30-day mortality were examined. Results Of the 82 adult patients investigated, 50 patients (61% had inflammatory diseases, 17 (21% had solid malignancies, 12 (15% had hematological malignancies, and 6 (7% had received transplantations. All patients received immunosuppressive agents or antitumor chemotherapeutic drugs. Plasma (1→3 β-D-glucan levels were elevated in 80% of patients, and were significantly reduced after treatment in both survivors and non-survivors. However, β-D-glucan increased in 18% of survivors and was normal in only 33% after treatment. Concomitant invasive pulmonary aspergillosis was detected in 5 patients. Fifty-six respiratory samples were stored for genotyping. A dihydropteroate synthase mutation associated with trimethoprim-sulfamethoxazole resistance was found in only 1 of the 53 patients. The most prevalent genotype of mitochondrial large-subunit rRNA was genotype 1, followed by genotype 4. The most prevalent genotype of internal transcribed spacers of the nuclear rRNA operon was Eb, followed by Eg and Bi. Thirty-day mortality was 24%, in which logistic regression analysis revealed association with serum albumin and mechanical ventilation, but no association with genotypes. Conclusions In non-HIV PCP, poorer general and respiratory conditions at diagnosis were independent predictors of mortality. β-D-glucan may not be useful for monitoring the response to treatment, and genotypes were not associated with mortality.

  14. Distribution and heterogeneity of hepatitis C genotypes in hepatitis patients in Cameroon.

    Science.gov (United States)

    Pasquier, Christophe; Njouom, Richard; Ayouba, Ahidjo; Dubois, Martine; Sartre, Michèle Tagni; Vessière, Aurelia; Timba, Isabelle; Thonnon, Jocelyn; Izopet, Jacques; Nerrienet, Eric

    2005-11-01

    Hepatitis C virus infects humans world-wide. The virus genome varies greatly and it has several genotypes. HCV infection is highly prevalent in Central Africa and Cameroon. Initial studies on the genetic variability of HCV showed infection with HCV genotypes 1, 2, and 4. We have now sequenced the NS5b and E2 regions of 156 HCV isolates collected from patients presenting for diagnosis in Yaounde and used the data to describe the distribution of HCV genotypes and subtypes in patients with hepatitis in Cameroon. Genotype 1 was more frequent than Genotypes 4 and 2. Genotypes 1 and 4 were highly heterogeneous, containing many subtypes described previously (1b, 1c, 1e, 1h, 1l, 4f, 4t, 4p, 4k) and unsubtyped groups. There was a systematic phylogenetic concordance between NS5b and E2 sequence clustering. The Genotype 2 sequences did not vary. Neither subject age nor gender influenced HCV distribution. HCV Genotypes 1 and 4 are very heterogeneous in Cameroon, perhaps due to ancient infections. The homogeneity of HCV Genotype 2 indicates its more recent introduction from western Africa.

  15. Distribution of hepatitis B virus genotypes in patients with chronic hepatitis B in Turkey

    Institute of Scientific and Technical Information of China (English)

    Mustafa Sunbul; Hakan Leblebicioglu

    2005-01-01

    AIM: Hepatitis B virus (HBV) strains isolated worldwide has been classified into eight genomic groups deduced from genome comparisons and designated as genotypes A to H. We aimed to investigate prevalence of HBV genotypes and subtypes in Turkey.METHODS: A total of 88 chronic hepatitis B (CHB) patients from 15 hospitals throughout the country were included.Patients who were HBsAg positive in serum at least for 6 mo, who had HBV-DNA in serum and elevation of ALT levels more than two times upper limit of normal, and who had percutaneous liver biopsy within 6 mo were included. Genotyping of HBV was done by restriction fragment length polymorphism (RFLP). The patients received subcutaneous 9 MU interferon-α 2a thrice a week for a period of 6 mo.RESULTS: Genotype D was detected in 78 of 88 (88.7%)patients, however, genotyping failed in two patients (2.3%),while no product was obtained in eight (9.0%) patients.Regarding subtypes, D2 was more prevalent (67 patients between 78% and 85.9%) followed by subtype D2+deletion (seven patients of 78 or 8.9%), subtype D1 (three patients of 78% or 3.9%) and subtype D3 (one patient of 78% or 1.3%). Thirty-three patients (37.5%) were HBeAg positive compared to 55 (62.5%) anti-HBe positive patients. The endpoint for the viral response of HBeAg positive patients was 27.2%, while it was found 52.7% in HBeAg negative patients (P<0.05). Long-term persistent viral response was 29.5% for all patients.CONCLUSION: This multi-center study indicates that the predominant genotype with CHB patients in Turkey like in other Mediterranean countries is genotype D.

  16. Genotype comparisons of strains of Candida albicans from patients with cutaneous candidiasis and vaginal candidiasis

    Institute of Scientific and Technical Information of China (English)

    SHE Xiao-dong; WANG Xue-jun; FU Mei-hua; SHEN Yong-nian; LIU Wei-da

    2008-01-01

    Background It is uncertain whether genotypes of Candida albicans (C. Albicans) are associated with colonizing body locations or variant conditions of infection. The aim of this study was to investigate whether there are significant associations between strain genotypes and body sites of infection and to determine the potential pathogenesis of cutaneous candidiasis at multiple locations.Methods A total of 151 strains of C. Albicans were isolated from 74 infant patients with cutaneous candidiasis and 61 female patients with vaginal candidiasis. Patients were grouped according to the body sites and underlying conditions of infection. Genolypes were identified by polymerase chain reaction (PCR) of the 25S rDNA and PCR-restriction fragment length polymorphism (RFLP) of ALT repeals digested with EcoRI and Clal.Results Ten genotypes were detected. There were significant differences in genotype frequencies between the two groups. However, we found no clear association between genotypes and the sites of cutaneous infection or the underlying conditions of vaginal candidiasis (VVC). In addition, strains of C. Albicans from multiple cutaneous locations of the same patient had identical genotypes.Conclusions Populations of C. Albicans from patients with cutaneous and vaginal candidiasis were genetically different. However, the lack of genetic difference between strains from different body sites with cutaneous infections or from different underlying conditions for VVC suggests no evidence of genotype selection for different skin surfaces or patients with different underlying conditions for VVC.

  17. The Distribution of Hepatitis C Virus Genotypes in Patients with Chronic Hepatitis C Infection

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    Sevin Kırdar

    2015-12-01

    Full Text Available Objective: Hepatitis C virus (HCV infection represents a major public health problem worldwide. HCV can cause chronic hepatitis infection which may ultimately result in cirrhosis and hepatocellular carcinoma. Seven major genotypes and more than 100 subtypes of HCV are shown by sequence analysis. Genotype 1 is associated with more severity of liver disease than genotypes 2 and 3 and sustained response totreatment is known to be less. In this study, we aimed to determine the HCV genotype distribution in chronic hepatitis C patients. Materials and Methods: A total of 50 patients with chronic HCV infection who attended the Microbiology Laboratory at Adnan Menderes University Hospital between August 2007 and December 2010 found to be positive for anti-HCV and HCV-RNA were included in the study. Anti-HCV testing was performed using microparticle Enzyme-Linked immunosorbent assay test kit (Murex Anti-HCV version 4, UK with autoanalyser (Grifols Triturus, Spain. The quantification of serum HCV-RNA was carried out by a realtime polymerase chain reaction method with two different systems (Cobas TaqMan HCV, Roche Diagnostics, Germany and RotorGene 6000,Corbett Research, USA. HCV genotype analysis was performed by using a kit (HCV-TS; AB Analitica, Italy based on the reverse hybridization of 5’-untranslated region and amplified products with genotype-specific probes. Results: The mean age of the 50 chronic hepatitis C patients [27 (54% female, and 23 (46% male] was 57.1±14.3 years. Genotype 1b was found in 36 (72% subjects, genotype 1a in nine (18%, genotype 2b in one (2%, genotype 3 in one (2%, and genotype 1a/1b was found in three (6% patients. No statistically significant difference was detected in HCV-RNA quantities and anti-HCV index between HCV genotypes (p>0.05. Conclusion: Compatible with the previous data obtained in Turkey, genotype 1b was found to be the most common HCV genotype in patients with chronic hepatitis C followed in our hospital.

  18. Hepatitis C virus genotypes among multiply transfused hemoglobinopathy patients from Northern Iraq

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    Adil A Othman

    2014-01-01

    Full Text Available Background and Aim: Owing to the scarcity of data on hepatitis C virus (HCV genotypes in Iraq and due to their epidemiological as well as therapy implications, this study was initiated aiming at determining these genotypes in Northern Iraq. Materials and Methods: A total of 70 HCV antibody positive multi transfused patients with hemoglobinopathies, who had detectable HCV ribonucleic acid, were recruited for genotyping using genotype-specific nested polymerase chain reaction. Results: The most frequent genotype detected was genotype 4 (52.9% followed by 3a (17.1%, 1b (12.9% and 1a (1.4%, while mixed genotypes (4 with either 3a or 1b were detected in 7.1%. Conclusion: The predominance of genotype 4 is similar to other studies from surrounding Eastern Mediterranean Arab countries and to the only earlier study from central Iraq, however the significant high proportion of 3a and scarcity of 1a, are in contrast to the latter study and may be explainable by the differing population interactions in this part of Iraq. This study complements previous studies from Eastern Mediterranean region and demonstrates relative heterogeneity of HCV genotype distribution within Iraq and should trigger further studies in other parts of the country.

  19. KIR genotype distribution among Lebanese patients with Hodgkin's lymphoma

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    Rouba Hoteit

    2015-06-01

    Conclusion: In this first study from the Mediterranean region, KIR genotype does not seem to be associated with Hodgkin's lymphoma. Further clinical and translational research is needed to rule out the protective or predisposing role of KIR genes in this important clinical entity.

  20. The Study of DNA Methyltransferase-3B Promoter Variant Genotype among Iranian Sporadic Breast Cancer Patients

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    Ebrahim Eftekhar

    2014-05-01

    Full Text Available Background: DNA methyltransferase-3B (DNMT3B is an important enzyme responsible for maintaining the DNA methylation pattern in eukaryotic cells. In this study we have investigated the correlation between the 46359C→T polymorphism in the DNMT3B gene and the risk of breast cancer incidence among sporadic breast cancer patients in Fars Province, Southern Iran. Methods: In this case-control study, 100 breast cancer patients and 138 healthy control subjects were genotyped for the DNMT3B gene by the polymerase chain reaction-restriction fragment length polymorphism method. Results: The genotype frequency in the case (CC 27%, CT 47%, TT 26% group significantly (P=0.008 differed from the control (CC 19.56%, CT 67.3%, TT 13% group. We observed a decreased association between the CT genotype and lymph node involvement in breast cancer patients. Our results have shown that in comparison to the homozygous CC genotype carriers the DNMT3B-CT genotype has a significantly lower risk for breast cancer (OR=0.515, 95% CI=0.267-0.994, P=0.048. Conclusion: Our case-control study showed that the CT genotype was significantly associated with decreased breast cancer risk. Consistent with these results, a significant decrease of CT genotype among lymph node positive breast cancer patients was observed. However, a larger study population with more clinical data is needed to confirm these results.

  1. Genotype characterization of occult hepatitis B virus strains among Egyptian chronic hepatitis C patients.

    Science.gov (United States)

    Kishk, R; Atta, H Aboul; Ragheb, M; Kamel, M; Metwally, L; Nemr, N

    2014-03-13

    Chronic hepatitis C virus (HCV) infection combined with occult hepatitis B virus (HBV) infection has been associated with increased risk of hepatitis, cirrhosis and hepatocellular carcinoma. This study aimed to determine the prevalence of occult HBV infection among Egyptian chronic HCV patients, the genotype and occurrence of surface gene mutations of HBV and the impact of co-infection on early response to treatment. The study enrolled 162 chronic HCV patients from Ismailia Fever Hospital, Egypt, who were HBV surface antigen-negative. All patients were given clinical assessment and biochemical, histological and virological examinations. HBV-DNA was detectable in sera from 3 patients out of the 40 patients who were positive for hepatitis B core antibody. These 3 patients were responsive to combination therapy at treatment week 12; only 1 of them had discontinued therapy by week 24. HBV genotype D was the only detectable genotype in those patients, with absence of "a" determinant mutations among those isolates.

  2. Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in Europe

    DEFF Research Database (Denmark)

    Soriano, Vincent; Mocroft, Amanda; Peters, Lars

    2010-01-01

    Both natural history and treatment outcome of hepatitis B virus (HBV) infection are influenced by genotypes and viral load. Information about factors determining HBV genotype distribution and viraemia in HIV/HBV-co-infected patients is scarce.......Both natural history and treatment outcome of hepatitis B virus (HBV) infection are influenced by genotypes and viral load. Information about factors determining HBV genotype distribution and viraemia in HIV/HBV-co-infected patients is scarce....

  3. Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients with chronic hepatitis B in Europe

    DEFF Research Database (Denmark)

    Soriano, Vincent; Mocroft, Amanda; Peters, Lars

    2010-01-01

    Both natural history and treatment outcome of hepatitis B virus (HBV) infection are influenced by genotypes and viral load. Information about factors determining HBV genotype distribution and viraemia in HIV/HBV-co-infected patients is scarce.......Both natural history and treatment outcome of hepatitis B virus (HBV) infection are influenced by genotypes and viral load. Information about factors determining HBV genotype distribution and viraemia in HIV/HBV-co-infected patients is scarce....

  4. Interleukin 10 gene single nucleotide polymorphisms in Polish patients with chronic hepatitis C: Analysis of association with severity of disease and treatment outcome.

    Science.gov (United States)

    Świątek-Kościelna, Bogna; Kałużna, Ewelina; Strauss, Ewa; Januszkiewicz-Lewandowska, Danuta; Bereszyńska, Iwona; Wysocki, Jacek; Rembowska, Jolanta; Barcińska, Dominika; Antosik, Dariusz; Mozer-Lisewska, Iwona; Nowak, Jerzy

    2017-02-01

    It is suggested that interleukin 10 (IL-10), as a modulator of immune response, is likely to influence the elimination of hepatitis C virus (HCV), the progression of chronic hepatitis C (CHC) and the response to interferon-based therapy in CHC patients. The aim of the study was to analyze the association of single nucleotide polymorphisms (SNPs) of IL-10 gene with severity of liver disease (degree of inflammation and stage of fibrosis) and outcome of pegylated interferon alpha and ribavirin combined therapy (sustained virological response (SVR) and relapse) in 196 Polish CHC patients infected with HCV genotype 1. The analysis included IL-10 promoter SNPs: -1082(A/G) rs1800896, -819(C/T) rs1800871, -592(C/A) rs1800872 and SNP in the 3' UTR of IL-10 gene: +4529(A/G) rs3024498. Genotyping was performed using PCR-RFLP and HRM analysis. It was demonstrated that the -592C allele is associated with mild hepatic inflammation. Moreover, it was found that the -819C allele might be associated with SVR and that the ACCA haplotype and intermediate IL-10 producer ACC haplotype are associated with SVR and non-relapse. It can be concluded that IL-10 SNPs are associated with severity of disease and response to therapy and may be considered as potential prognostic and predictive markers in CHC.

  5. Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide

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    Martin Javorský

    2013-01-01

    Full Text Available Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1 with sulfonylureas binding to AB-site (Group 2. A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the previous metformin treatment. TCF7L2 rs7903146 C/T genotype was identified by real-time PCR with subsequent melting curve analysis. Analyses using the dominant genetic model showed significantly higher effect of gliclazide in the CC genotype group in comparison with combined CT + TT genotype group (1.32±0.15% versus 0.73±0.11%, Padj=0.005. No significant difference in ΔHbA1c between the patients with CC genotype and the T-allele carriers was observed in Group 2. In the multivariate analysis, only the TCF7L2 genotype (P=0.006 and the baseline HbA1c (P<0.001 were significant predictors of ΔHbA1c. After introducing an interaction term between the TCF7L2 genotype and the sulfonylurea type into multivariate model, the interaction became a significant predictor (P=0.023 of ΔHbA1c. The results indicate significantly higher difference in ΔHbA1c among the TCF7L2 genotypes in patients treated with gliclazide than in patients treated with glimepiride, glibenclamide, or glipizide.

  6. Different norovirus genotypes in patients with gastroenteritis in Kuwait.

    Science.gov (United States)

    Al-Rashidi, Amirah; Chehadeh, Wassim; Szücs, György G; Albert, M John

    2013-09-01

    Norovirus is a leading cause of acute gastroenteritis worldwide. The importance of this virus infection in Kuwait is not known. Eight out of 100 stool samples (8.0%) from children up to 5 years of age with gastroenteritis studied during 2006-2007 from one hospital, and 6 out of 70 stool samples (8.5%) from similar children studied from another hospital during 2010-2011 were positive for norovirus by RT-PCR. Out of these 170 samples studied from both hospitals, 10 samples were positive for norovirus when tested by ELISA. Phylogenetic tree analysis of norovirus strains showed that 50% of the norovirus strains belonged to genotype GII.4, and the predominant strain was GII.4 2006b. Other detected genotypes were GII.12, GII.b, GII.3, GII.8, and GII.7. This study highlights the importance of screening for norovirus infection in acute gastroenteritis and having a reporting system to understand better the epidemiology of norovirus infection in Kuwait.

  7. Helicobacter pylori genotyping from positive clotests in patients with duodenal ulcer

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    Mattar Rejane

    2000-01-01

    Full Text Available Even though the seroprevalence of H. pylori may be high in the normal population, a minority develops peptic ulcer. Colonization of the gastric mucosa by more pathogenic vacA strains of H. pylori seems to be associated with enhanced gastric inflammation and duodenal ulcer. H. pylori genotyping from positive CLOtests was developed to determine the vacA genotypes and cagA status in 40 duodenal ulcer patients and for routine use. The pathogenic s1b/ m1/ cagA genotype was the most frequently occurring strain (17/42.5%; only two (5% patients presented the s2/ m2 genotype, the less virulent strain. Multiple strains were also detected in 17 (42.5% patients. Multiple strains of H. pylori colonizing the human stomach have been underestimated, because genotyping has been performed from cultures of H. pylori. We concluded that genotyping of H. pylori from a positive CLOtest had the advantages of reducing the number of biopsies taken during endoscopy, eliminating the step of culturing H. pylori, and assuring the presence of H. pylori in the specimen being processed.

  8. Genotyping of occult hepatitis B virus infection in Egyptian hemodialysis patients without hepatitis C virus infection.

    Science.gov (United States)

    Esmail, Mona A; Mahdi, Wafaa K M; Khairy, Rasha M; Abdalla, Nilly H

    2016-01-01

    Occult hepatitis B viral infection is the presence of hepatitis B viral nucleic acids in the serum and/or liver in the absence of hepatitis B surface antigen. The study aimed to determine the prevalence of occult hepatitis B virus infection among hepatitis C virus-negative hemodialysis patients and to identify their genotypes. of 144 patients on maintenance hemodialysis, 50 hepatitis B surface antigen and hepatitis C virus nucleic acid-negative patients were selected according to strict inclusion criteria to avoid the effect of confounding variables. The following investigations were done: serum AST and ALT; HBsAg; HBcAb; HCV-Ab; HCV-RNA; and HBV-DNA. Positive hepatitis B viral nucleic acid was confirmed in 12/144 (8.3%) hemodialysis patients and 12/50 (24%) in our study group (occult infection). Mean hemodialysis periods for negative patients and occult hepatitis B virus patients were 27.3±18.8 and 38.4±8.14 months, respectively, and this difference was significant (p-value=0.02). Mean alanine transaminase levels were 20.27±5.5IU/L and 25.3±9.6 in negative patients and occult infection patients, respectively. This difference was non-significant. Aspartate transaminase levels were 21.4±10.2IU/L and 27.3±4.6IU/L, respectively, in negative patients and infected patients; this difference was significant (p-value=0.03). Half (6/12) of the positive samples belonged to genotype 'B', 33.3% (4/12) to 'C', and 16.6% (2/12) to genotype 'D'. OBI is likely among hemodialysis patients even without HCV coinfection (24%). Genotype D cannot be the only genotype distributed in Upper Egypt, as the current study reported relatively new results that 50% of the patients with occult B carry genotype B, 33.3% carry genotype C and only 16.6% carry genotype D. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  9. Risk Factors and Genotypes of Hepatitis C Virus Infection in Libyan Patients

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    Alashek WA

    2008-01-01

    Full Text Available Background: The prevalence and incidence of HCV infection varies geographically due to exposureto different risk factors. Identification of HCV genotype is important to defining the epidemiology of thedisease. The objective of this study was to describe genotype distribution and its relation to riskfactors among HCV infected patients attending virology clinic of the Department of InfectiousDiseases at the Tripoli Medical Centre. Methods: The medical records of 891 Libyan chronic HCVinfected patients registered and followed up from January 2003 to January 2007 were reviewed. Datagathered includes patient's age, gender, risk factors and family history of HCV infection. Statisticalanalysis was performed using t, x2 and contingency coefficient tests. Results: The mean age was40.22±13.09 years. Two thirds of patients were males. Normal alanine aminotransferase (ALT atdiagnosis was found in 62% of the patients. HCV RNA < 2 million copies at diagnosis was foundamong 54% of patients. HCV genotype 1 (G1 was the most frequent (30.9%, followed by G4(29.2%. Genotype 2 affected 19.3% and G3 13.6%. No classification of HCV genotype was availablefor 2% of the patients. Many subtypes of HCV were detected with different frequencies (G1a and b,G2a, b, c and a/c, G3a and G4a and c/d. All genotypes of HCV were more common among males(P<0.001. Genotype 3 was the most frequent among male patients (88.6%. Regarding the riskfactors, 33% of patients had a history of hospitalization and/or surgical procedures, and 22.7% had ahistory of blood transfusion. A past history of intravenous drug abuse (IVDA was reported by 15% ofthe patients, and 15.9% reported a history of dental procedures. The relationship between thegenotype of HCV and risk factors was statistically significant (P<0.001. No history of risky exposurewas found among 10.8% of patients. Conclusion: Genotypes 1 and 4 were more predominantamong HCV infected patients. Males were affected more than females and

  10. Mycobacterium tuberculosis strains of the Beijing genotype are rarely observed in tuberculosis patients in South America

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    Viviana Ritacco

    2008-08-01

    Full Text Available The frequency of the Beijing genotype of Mycobacterium tuberculosis as a cause of tuberculosis (TB in South America was determined by analyzing genotypes of strains isolated from patients that had been diagnosed with the disease between 1997 and 2003 in seven countries of the subcontinent. In total, 19 of the 1,202 (1.6% TB cases carried Beijing isolates, including 11 of the 185 patients from Peru (5.9%, five of the 512 patients from Argentina (1.0%, two of the 252 Brazilian cases (0.8%, one of the 166 patients from Paraguay (0.6% and none of the samples obtained from Chile (35, Colombia (36 and Ecuador (16. Except for two patients that were East Asian immigrants, all cases with Beijing strains were native South Americans. No association was found between carrying a strain with the Beijing genotype and having drug or multi-drug resistant disease. Our data show that presently transmission of M. tuberculosis strains of the Beijing genotype is not frequent in Latin America. In addition, the lack of association of drug resistant TB and infection with M. tuberculosis of the Beijing genotype observed presently demands efforts to define better the contribution of the virulence and lack of response to treatment to the growing spread of Beijing strains observed in other parts of the world.

  11. Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China

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    Ines Pinto-Ribeiro

    2016-05-01

    Full Text Available Helicobacter pylori is the major triggering factor for gastric carcinoma, but only a small proportion of infected patients develop this disease. Differences in virulence observed among H. pylori strains, namely in the vacuolating cytotoxin vacA gene, may contribute to this discrepancy. Infection with vacA s1, i1 and m1 strains increases the risk for progression of gastric premalignant lesions and for gastric carcinoma. However, in East Asian countries most of the H. pylori strains are vacA s1, regardless of the patients’ clinical status, and the significance of the vacA i1 and m1 genotypes for gastric carcinoma in this geographic area remains to be fully elucidated. The aim of the present study was to investigate this relationship in 290 patients from Macau, China. Using very sensitive and accurate genotyping methods, we detected infection with vacA i1 and with vacA m1 strains in, respectively, 85.2% and 52.6% of the patients that were infected with single genotypes. The prevalence of cagA-positive strains was 87.5%. No significant associations were observed between vacA genotypes or cagA and gastric carcinoma. It is worth noting that 37.5% of the infected patients had coexistence of H. pylori strains with different vacA genotypes. Additional studies directed to other H. pylori virulence factors should be performed to identify high risk patients in East Asia.

  12. Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype.

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    Goolsby Hunter, Alyssa; Rosenblatt, Lisa; Patel, Chad; Blauer-Peterson, Cori; Anduze-Faris, Beatrice

    2017-05-01

    In the United States, approximately 3 million people are infected with hepatitis C virus (HCV). Genotypes of HCV variably affect disease progression and treatment response. However, the relationships between HCV genotypes and liver disease progression, healthcare resource utilization, and healthcare costs have not been fully explored. In this retrospective study of patients with chronic hepatitis C (CHC), healthcare claims from a large US health plan were used to collect data on patient demographic and clinical characteristics. Main outcome measures include healthcare resource utilization (HCRU) and healthcare costs. Linked laboratory data provided genotype and select measures to determine liver disease severity. The sample (mean age 50.6 years, 63.5% male) included 10,331 patients, of whom 79.1% had genotype (GT)1, 12.8% had GT2, and 8.1% had GT3. Descriptive analyses demonstrated variation by HCV genotype in liver and non-liver related comorbidities, liver disease severity, and healthcare costs. The highest percentage of patients with liver-related comorbidities and advanced liver disease was found among those with GT3. Meanwhile, patients with GT2 had lower HCRU and the lowest costs, and patients with GT1 had the highest total all-cause costs. These differences may reflect differing rates of non-liver-related comorbidities and all-cause care. Multivariable analyses showed that genotype was a significant predictor of costs and liver disease severity: compared with patients having GT1, those with GT3 were significantly more likely to have advanced liver disease. Patients with GT2 were significantly less likely to have advanced disease and more likely to have lower all-cause costs. Results may not be generalizable to patients outside the represented commercial insurance plans, and analysis of a prevalent population may underestimate HCRU and costs relative to a sample of treated patients. These results suggest that liver disease progression varies by genotype and

  13. High prevalence of ACE DD genotype among north Indian end stage renal disease patients

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    Pandirikkal Baburajan Vinod

    2006-10-01

    Full Text Available Abstract Background The Renin-Angiotensin system (RAS is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1 is an important component of RAS which determines the vasoactive peptide Angiotensin-II. Methods In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8 and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease determined from the serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain reaction (PCR based DNA amplification using specific flanking primers Based on the method described elsewhere. Results The difference of DD and II genotypes was found highly significant among the two groups (p = 0.025; OR = 3.524; 95%CI = 1.54-8.07. The combined genotype DD v/s ID+II comparison validated that DD genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95%CI limit = 3.4-8.5. However, no correlation was obtained for different biochemical parameters of lipid profile and renal function among DD and non DD genotype. Interestingly, ~87% of the DD ESRD patients were found hypertensive in comparison to the 65% patients of non DD genotype Conclusion Based on these observations we conclude that ACE DD genotype implicate a strong possible role in the hypertensive state and in renal damage among north Indians. The study will help in

  14. Occurrence of pathogenic Acanthamoeba genotypes in nasal swabs of cancer patients in Iran.

    Science.gov (United States)

    Memari, Fatemeh; Niyyati, Maryam; Haghighi, Ali; Seyyed Tabaei, Seyyed Javad; Lasjerdi, Z

    2015-05-01

    Incidences of Acanthamoeba granulomatous encephalitis (AGE) have been increased due to a rise in the number of high-risk people, such as immunodeficient patients. Indeed, immunosuppress situation can render the patient in acquiring opportunistic Acanthamoeba infections. In this study, analysis was carried out to verify the presence of free-living amoebae of Acanthamoeba genus in nasal swabs of cancer patients in hospitals of Tehran, Iran. Detection of isolates was based on morphotyping and PCR sequencing of the Diagnostic Fragment 3 (DF3) to identify strains at the genotype level. In addition, the pathogenic potential of the isolates was assayed using temperature and osmotolerance assays. The obtained results revealed that nine isolated strains belonging to T4 genotype-exhibited pathogenic potential. After sequencing, genotype T4 was found to be the most common one in the samples included in this study. Genotype T3 and T5 were also identified. To the best of our knowledge, this is the first study on the typing of Acanthamoeba strains at the genotype level in cancer patients in Iran and worldwide.

  15. Characterization of multiple isolates of Aspergillus fumigatus from patients: genotype, mating type and invasiveness.

    Science.gov (United States)

    Alvarez-Perez, Sergio; Garcia, Marta E; Bouza, Emilio; Pelaez, Teresa; Blanco, Jose L

    2009-01-01

    The possible co-existence of different genotypes of Aspergillus fumigatus in the same case was studied in five patients colonized or infected by this opportunistic mould. A total of 22 isolates were typed by random amplified polymorphic DNA (RAPD) and microsatellite analysis. Differences in the mating type and invasiveness of the isolates were also considered. The combination of four arbitrary primers used in RAPD typing differentiated all the isolates. In microsatellite analysis, at least two different genotypes were identified in four of the five patients. The 22 isolates showed elastase activity after 10 days of incubation at 37 degrees C in an elastin-containing medium. The presence of strains of compatible mating type was observed in one of the colonized patients and one of the individuals with invasive aspergillosis. Some isolates that belonged to the same genotype in microsatellite analysis were of a different mating type. Taken together, our results suggest that multiple isolates of A. fumigatus obtained from colonized or infected patients may differ not only in their genotypes, but also in their invasiveness and mating types. Furthermore, mating type determination may be of great assistance in differentiating some isolates, as two isolates of different mating type cannot be genotypically identical.

  16. Transfusion-transmitted virus infection in hemodialysis patients in Arar, Saudi Arabia: Prevalence, predictors and genotyping

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    Sheref M El-taher

    2015-01-01

    Full Text Available Transfusion-transmitted virus (TTV is a single-stranded DNA virus that was identified in patients with post-transfusion hepatitis of non-A-to-G type. Patients with chronic renal failure on maintenance hemodialysis (HD have a higher risk of viral infections, and the prevalence of TTV infection is common. The aim of our study was to detect TTV-DNA and its genotype in HD patients. A case-control study compromising of 63 patients on maintenance HD therapy at the Nephrology Center of Central Arar Hospital and 100 healthy individuals who were tested for TTVDNA and its genotype by semi nested-polymerase chain reaction with primers derived from the conserved open reading frame 1 (ORF1 region followed by digestion with NdeI and PstI restriction enzyme. The results show that the prevalence of TTV in HD patients was high and statistically significant; 42.9% compared with 19% in the control group. History of blood transfusion was the only significant predictor, and we found that age of patients, duration of HD, hepatitis B and C infection, aspartate aminotransferase and alanine aminotransferase levels were not significant predictors of TT virus positivity in HD patients. TTV genotype 1 (G1 was found to be the most common genotype among both HD and healthy controls. The prevalence of TTV among HD patients was significantly higher than that in healthy individuals. History of blood transfusion was the only significant predictor of TTV positivity among them. Genotype 1 was the most predominant type among HD and healthy individuals. Further studies on TTV in peritoneal dialysis patients and transplant patients are needed.

  17. Prevalence of transfusion transmitted virus (TTV genotypes among HCC patients in Qaluobia governorate

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    Salim Rabab F

    2007-12-01

    Full Text Available Abstract Background Transfusion Transmitted virus (TTV is a novel single-stranded DNA virus that was identified in patients with post-transfusion hepatitis of non-A-G type. Clinical significance of TTV infection was analyzed in Egyptian hepatocellular carcinoma (HCC patients. The present study attempted to clarify these issues in Egypt, particularly in Qaluobia governorate, a country known for its high endemicity of liver disease and hepatotropic viruses. Methods TTV are determined in the serum of 60 samples obtained from HCC and liver cirrhosis (LC patients and 30 healthy individuals. TTV DNA is amplified by nested-PCR with TTV-specific mixed primers derived from the conserved open reading frame 1 (ORF1 region followed by digestion with restriction enzyme. Using the enzymes HaeIII, DraI, EcoRI and PstI, we are able to distinguish between the four TTV genotypes. Results The positive rate of TTV detection was 46.7%, 40% and 36.7% among HCC, LC patients and healthy individuals respectively. The more prevalence genotype was detected in the positive serum samples was genotype 1 (35.7% in HCC patients, (50% in LC and (63.3% in healthy individuals, Genotype 5 (21.4%, (25.5% and (18.2% in HCC, LC and healthy individuals respectively. Discussion This study indicates that TTV is commonly present in adult patients with HCC and LC as well as healthy individuals. The most prevalence TTV genotype is genotype 1. It seems that the infection neither contribute to the severity of liver disease no to the causation of HCC.

  18. Genotypes of Invasive Pneumococcal Isolates Recently Recovered from Italian Patients

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    Dicuonzo, Giordano; Gherardi, Giovanni; Gertz, Robert E.; D'Ambrosio, Fabio; Goglio, Antonio; Lorino, Giulia; Recchia, Simona; Pantosti, Annalisa; Beall, Bernard

    2002-01-01

    We examined 73 recent invasive pneumococcal isolates within selected areas of Italy for genotypic variability. Thirty-three genomic macrorestriction types were found, three of which represented multiple serotypes. Restriction fragment patterns of pbp2b, pbp2x, and pspA were conserved within the majority of isolates that shared macrorestriction types. Of the nine macrorestriction types found among the 22 penicillin-nonsusceptible Streptococus pneumoniae (PNSP) isolates, seven comprised isolates with allelic profiles showing five to seven allelic matches to profiles in the multilocus sequence typing database (www.mlst.net); however, three of the seven profiles represented serotypes not previously associated with these clonal clusters. Two PNSP macrorestriction types represented new clones with unique allelic profiles. Allelic profiles obtained from isolates of 3 of the 25 macrorestriction types found among the 51 penicillin-susceptible S. pneumoniae (PSSP) isolates were closely related to previously described profiles. One PSSP isolate was a novel type 24F isolate related to the multiresistant clone France9V-3. This work reports new PNSP strains and new serotype-clone associations. PMID:12354862

  19. Successful Treatment of Mixed Hepatitis C Genotypes in a Cirrhotic Patient With an All-Oral, Interferon-Free Regimen

    Science.gov (United States)

    Ahmed Sakr, Ayman; Hanifi, Jasmine M.

    2017-01-01

    Mixed hepatitis C virus (HCV) genotype infection is emerging with improved methods of detection. It is commonly seen in hemodialysis patients and intravenous drug users due to repeated HCV exposure and absence of protective immunity, and can contribute to treatment failure. Direct-acting antiviral regimens have been extensively studied in patients with different individual HCV genotypes; however, there are no reported data on their use in patients with mixed HCV genotype. We present a case of mixed HCV genotype 1a and 2 infection in a decompensated cirrhotic patient treated successfully with sofosbuvir, ledipasvir, and ribavirin. PMID:28184373

  20. Molecular epidemiology, genotype-phenotype correlation and BH4 responsiveness in Spanish patients with phenylketonuria.

    Science.gov (United States)

    Aldámiz-Echevarría, Luis; Llarena, Marta; Bueno, María A; Dalmau, Jaime; Vitoria, Isidro; Fernández-Marmiesse, Ana; Andrade, Fernando; Blasco, Javier; Alcalde, Carlos; Gil, David; García, María C; González-Lamuño, Domingo; Ruiz, Mónica; Ruiz, María A; Peña-Quintana, Luis; González, David; Sánchez-Valverde, Felix; Desviat, Lourdes R; Pérez, Belen; Couce, María L

    2016-08-01

    Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

  1. Increased hepatic expression of miRNA-122 in patients infected with HCV genotype 3.

    Science.gov (United States)

    Oliveira, Ketti G; Malta, Fernanda M; Nastri, Ana C S S; Widman, Azzo; Faria, Paola L; Santana, Rúbia A F; Alves, Venâncio A F; Carrilho, Flair J; Pinho, João R R

    2016-04-01

    Hepatitis C virus (HCV) infection affects approximately 3 % of the world population. HCV targets hepatic tissue, and most infected patients develop a chronic infection. Currently, studies have demonstrated an association between HCV-RNA replication and miR-122, the most abundant microRNA in the liver. Our aim was to evaluate liver and serum expression of miR-122 in patients infected with HCV genotypes 1 and 3, and to identify possible associations between miR-122 expression and lipid profiles, HCV viral load, apolipoproteins and liver enzymes. MicroRNAs were isolated from blood and liver tissue, and miR-122 expression was quantified by real-time PCR. HCV viral load was quantified by real-time PCR and HCV genotype, and serum biomarkers were obtained from medical report. The levels of miR-122 were higher in liver than those in blood from individuals infected with HCV genotypes 1 and 3 (p HCV genotype 3 (6.22-fold, p HCV genotype 1 (r = 0.302, p = 0.026); in these patients, an inverse correlation was observed between serum apolipoprotein A-II (ApoA-II) levels and the blood (r = -0.330; p = 0.014) and hepatic (r = -0.311; p = 0.020) levels of miR-122. In patients infected with HCV genotype 3, there was a positive correlation between the hepatic miR-122 and the high-density lipoprotein-HDL (r = 0.412, p = 0.036) and insulin (r = 0.478, p = 0.044). Lipid metabolism proteins and miR-122 expression levels have different relations in HCV-3- and HCV-1-infected patients.

  2. Lewis blood genotypes of peptic ulcer and gastric cancer patients in Taiwan

    Institute of Scientific and Technical Information of China (English)

    Chi-Jung Yei; Jan-Gowth Chang; Mu-Chin Shih; Sheng-Fung Lin; Chao-Sung Chang; Fu-Tsong Ko; Kuang-Yang Lin; Ta-Chin Liu

    2005-01-01

    AIM: The Lewis b (Leb) antigen has been implicated as a possible binding site for attachment of Helicobacter pylori (H pylori)to gastric mucosa. However, studies both supporting and denying this association have been reported in the literature. Differences in secretor (Se)genotype have been suggested as a possible reason for previous discrepancies. Therefore, we investigated the relationship between Le and Se genotypes and H pylori infection rates in people with peptic ulcer or gastric cancer.METHODS: Peripheral blood samples were obtained from 347 patients with endoscopic evidence of peptic ulcer disease (235 cases of duodenal ulcer, 62 of gastric ulcer,and 50 of combined duodenal ulcer/gastric ulcer) and 51patients with gastric cancer on endoscopy. Peripheral blood specimens from 101 unrelated normal volunteers were used as controls. Lewis phenotype was determined using an antibody method, whereas Le and Se genotypes were determined by DNA amplification and restriction enzyme analysis. Gastric or duodenal biopsies taken from patients with endoscopic evidence of peptic ulcer or gastric cancer were cultured for H pylori. Isolates were identified as H pylori by morphology and production of urease and catalase. The H pylori infection status was also evaluated by rapid urease test (CLO test), and urea breath test (13C-UBT). Results of studies were analyzed by chi-square test (taken as significant).RESULTS: H pyloriwas isolated from 83.7% (303/347)of patients with peptic ulcer disease. Statistical analysis did not show any significant difference in Lewis phenotype or genotype between patients with and without H pylori infection. No significant association was found between Lewis genotype and peptic ulcer or gastric cancer.CONCLUSION: Lewis blood genotype or phenotype may not play a role in the pathogenesis of H pyloriinfection.However, bacterial strain differences and the presence of more than one attachment mechanism may limit the value of epidemiological studies in

  3. Cost-effectiveness analysis of sofosbuvir compared to current standard treatment in Swiss patients with chronic hepatitis C.

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    Alena M Pfeil

    Full Text Available In clinical trials, sofosbuvir showed high antiviral activity in patients infected with hepatitis C virus (HCV across all genotypes. We aimed to determine the cost-effectiveness of sofosbuvir-based treatment compared to current standard treatment in mono-infected patients with chronic hepatitis C (CHC genotypes 1-4 in Switzerland. Cost-effectiveness was modelled from the perspective of the Swiss health care system using a lifetime Markov model. Incremental cost-effectiveness ratios (ICERs used an endpoint of cost per quality-adjusted life year (QALY gained. Treatment characteristics, quality of life, and transition probabilities were obtained from published literature. Country-specific model inputs such as patient characteristics, mortality and costs were obtained from Swiss sources. We performed extensive sensitivity analyses. Costs and effects were discounted at 3% (range: 0-5% per year. Sofosbuvir-containing treatment in mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1-4 showed ICERs between CHF 10,337 and CHF 91,570 per QALY gained. In subgroup analyses, sofosbuvir dominated telaprevir- and boceprevir-containing treatment in treatment-naïve genotype 1 cirrhotic patients. ICERs of sofosbuvir were above CHF 100,000 per QALY in treatment-naïve, interferon eligible, non-cirrhotic patients infected with genotypes 2 or 3. In deterministic and probabilistic sensitivity analyses, results were generally robust. From a Swiss health care system perspective, treatment of mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1-4 with sofosbuvir-containing treatment versus standard treatment would be cost-effective if a threshold of CHF 100,000 per QALY was assumed.

  4. Cost-effectiveness analysis of sofosbuvir compared to current standard treatment in Swiss patients with chronic hepatitis C.

    Science.gov (United States)

    Pfeil, Alena M; Reich, Oliver; Guerra, Ines M; Cure, Sandrine; Negro, Francesco; Müllhaupt, Beat; Lavanchy, Daniel; Schwenkglenks, Matthias

    2015-01-01

    In clinical trials, sofosbuvir showed high antiviral activity in patients infected with hepatitis C virus (HCV) across all genotypes. We aimed to determine the cost-effectiveness of sofosbuvir-based treatment compared to current standard treatment in mono-infected patients with chronic hepatitis C (CHC) genotypes 1-4 in Switzerland. Cost-effectiveness was modelled from the perspective of the Swiss health care system using a lifetime Markov model. Incremental cost-effectiveness ratios (ICERs) used an endpoint of cost per quality-adjusted life year (QALY) gained. Treatment characteristics, quality of life, and transition probabilities were obtained from published literature. Country-specific model inputs such as patient characteristics, mortality and costs were obtained from Swiss sources. We performed extensive sensitivity analyses. Costs and effects were discounted at 3% (range: 0-5%) per year. Sofosbuvir-containing treatment in mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1-4 showed ICERs between CHF 10,337 and CHF 91,570 per QALY gained. In subgroup analyses, sofosbuvir dominated telaprevir- and boceprevir-containing treatment in treatment-naïve genotype 1 cirrhotic patients. ICERs of sofosbuvir were above CHF 100,000 per QALY in treatment-naïve, interferon eligible, non-cirrhotic patients infected with genotypes 2 or 3. In deterministic and probabilistic sensitivity analyses, results were generally robust. From a Swiss health care system perspective, treatment of mixed cohorts of cirrhotic and non-cirrhotic patients with CHC genotypes 1-4 with sofosbuvir-containing treatment versus standard treatment would be cost-effective if a threshold of CHF 100,000 per QALY was assumed.

  5. A cross-battery, reference variable, confirmatory factor analytic investigation of the CHC taxonomy.

    Science.gov (United States)

    Reynolds, Matthew R; Keith, Timothy Z; Flanagan, Dawn P; Alfonso, Vincent C

    2013-08-01

    The Cattell-Horn-Carroll (CHC) taxonomy has been used to classify and describe human cognitive abilities. The ability factors derived from the CHC taxonomy are often assumed to be invariant across multiple populations and intelligence batteries, which is an important assumption for research and assessment. In this study, data from five different test batteries that were collected during separate Kaufman Assessment Battery for Children-Second Edition (KABC-II; Kaufman & Kaufman, 2004) concurrent validity studies were factor-analyzed jointly. Because the KABC-II was administered to everyone in the validity studies, it was used as a reference battery to link the separate test batteries in a "cross-battery" confirmatory factor analysis. Some findings from this analysis were that CHC-based test classifications based on theory and prior research were straightforward and accurate, a first-order Fluid/Novel Reasoning (Gf) factor was equivalent to a second-order g factor, and sample heterogeneity related to SES and sex influenced factor loadings. It was also shown that a reference variable approach, used in studies that incorporate planned missingness into data collection, may be used successfully to analyze data from several test batteries and studies. One implication from these findings is that CHC theory should continue to serve as a useful guide that can be used for intelligence research, assessment, and test development.

  6. Lamivudine resistance mutations in patients infected with hepatitis B virus genotype D

    Institute of Scientific and Technical Information of China (English)

    Orhan Y(l)ld(l)z; Bilgehan Aygen; Nese Demirtürk; Tuna Demirdal; Dilara Inan; Taner Y(l)ld(l)rmak; Arzu Kantürk; Ediz Tütüncü

    2011-01-01

    AIM: To determine the distribution of viral genotypes for primary or acquired lamivudine resistance. METHODS: A total of 283 patients with chronic hepatitis B virus (HBV) infection (245 patients with chronic hepatitis B and 38 inactive hepatitis B surface antigen carriers) were included in the study. The HBV genotype was determined by using quantitative real-time polymerase chain reaction and sequence analysis, and tyrosine-methionine-aspartate-aspartate (YMDD) motif mutations were determined using the reverse transcriptase hybridization method. RESULTS: Lamivudine resistance was determined in a total of 25 (10.7%) chronic hepatitis B patients. Eight subjects (4%) had primary resistance to lamivudine, and 17 (53.1%) had secondary resistance to lamivudine. Genotype D, which was isolated from 267 of the patients with chronic HBV infection, was the dominant genotype in Turkey.CONCLUSION: Identification of YMDD motif mutations should have a positive impact on the selection of proper antiviral medication for patients, even for those who are nucleoside na(i)ve.

  7. Hepatitis B virus infection profile in hemodialysis patients in Central Brazil: prevalence, risk factors, and genotypes

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    Renata C Ferreira

    2006-09-01

    Full Text Available Hemodialysis patients are at high risk for hepatitis B virus (HBV infection. A survey was conducted in the hemodialysis population of the state of Goiás, Central Brazil, aiming to assess the prevalence of HBV infection, to analyse associated risk factors, and also to investigate HBV genotypes distribution. A total of 1095 patients were interviewed in 15 dialysis units. Serum samples were screened for HBV serological markers by enzyme-linked immunosorbent assay. Hepatitis B surface antigen (HBsAg positive samples were tested for HBV DNA by polymerase chain reaction and genotyped by restriction fragment length polymorphism. Global HBV infection prevalence was 29.8% (95% CI: 27.1-32.5. Multivariate analysis of risk factors showed that male gender, length of time on hemodialysis, and blood transfusion before 1993 were associated with HBV positivity. HBV DNA was detected in 65.4% (17/26 of the HBsAg-positive samples. Thirteen of 17 HBV DNA positive samples were genotyped. Genotype D (61.5% was predominant, followed by A (30.8%, while genotype F was detected in only one (7.7% sample.

  8. Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

    Institute of Scientific and Technical Information of China (English)

    Perdita Wietzke-Braun; Volker Meier; Katrin Neubauer-Saile; Sabine Mihm; Giuliano Ramadori

    2005-01-01

    AIM: Before pegylated interferon alpha (IFN) was introduced for the therapy of chronic hepatitis C virus(HCV)-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time,higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C.METHODS: Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 (n = 12) were treated for 24 wk, and patients with genotypes other than 2 or 3 (n = 34) for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment (EOT).Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received RESULTS: During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients (n = 9) infected with genotype 2 or 3showed an initial virological response rate of 100%. Six patients (66.7%) were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed(33.3%). In comparison, patients infected with genotypes other than 2 or 3 (n = 34) showed an initial virological response rate of only 23.5% (n = 8), and even in combination with ribavirin a sustained virological response(SVR) rate of only 11.8% (n = 4) could be achieved.CONCLUSION: In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment

  9. Hepatitis E Virus Genotype 3 in Colombia: Survey in Patients with Clinical Diagnosis of Viral Hepatitis

    Science.gov (United States)

    Rendon, Julio; Hoyos, Maria Cristina; di Filippo, Diana; Cortes-Mancera, Fabian; Mantilla, Carolina; Velasquez, Maria Mercedes; Sepulveda, Maria Elsy; Restrepo, Juan Carlos; Jaramillo, Sergio; Arbelaez, Maria Patricia; Correa, Gonzalo; Navas, Maria-Cristina

    2016-01-01

    Background Hepatitis E virus is a major cause of outbreaks as well as sporadic hepatitis cases worldwide. The epidemiology of this enterically transmitted infection differs between developing and developed countries. The aims of this study were to describe HEV infection in Colombian patients and to characterize the genotype. Methods A prospective study was carried out on 40 patients aged over 15 with a clinical diagnosis of viral hepatitis, recruited from five primary health units in the city of Medellin, Colombia. Fecal samples obtained from the 40 consecutives cases were analyzed for HEV RNA using nested reverse transcription PCR for both ORF1 and ORF2-3. The amplicons were sequenced for phylogenetic analyses. Results Nine (22.5%) cases of HEV infection were identified in the study population. Three HEV strains obtained from patients were classified as genotype 3. No significant association was found between cases of Hepatitis E and the variables water drinking source, garbage collection system and contact with pigs. Conclusions This is the first prospective study of hepatitis E in Colombian patients. The circulation of the genotype 3 in this population is predictable considering the reports of the region and the identification of this genotype from pigs in the state of Antioquia, of which Medellin is the capital. Further studies are necessary to establish whether zoonotic transmission of HEV is important in Colombia. PMID:26886728

  10. Hepatitis E Virus Genotype 3 in Colombia: Survey in Patients with Clinical Diagnosis of Viral Hepatitis.

    Directory of Open Access Journals (Sweden)

    Julio Rendon

    Full Text Available Hepatitis E virus is a major cause of outbreaks as well as sporadic hepatitis cases worldwide. The epidemiology of this enterically transmitted infection differs between developing and developed countries. The aims of this study were to describe HEV infection in Colombian patients and to characterize the genotype.A prospective study was carried out on 40 patients aged over 15 with a clinical diagnosis of viral hepatitis, recruited from five primary health units in the city of Medellin, Colombia. Fecal samples obtained from the 40 consecutives cases were analyzed for HEV RNA using nested reverse transcription PCR for both ORF1 and ORF2-3. The amplicons were sequenced for phylogenetic analyses.Nine (22.5% cases of HEV infection were identified in the study population. Three HEV strains obtained from patients were classified as genotype 3. No significant association was found between cases of Hepatitis E and the variables water drinking source, garbage collection system and contact with pigs.This is the first prospective study of hepatitis E in Colombian patients. The circulation of the genotype 3 in this population is predictable considering the reports of the region and the identification of this genotype from pigs in the state of Antioquia, of which Medellin is the capital. Further studies are necessary to establish whether zoonotic transmission of HEV is important in Colombia.

  11. HIV-1 genotypic resistance profile of patients failing antiretroviral therapy in Paraná, Brazil

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    Paula Virginia Michelon Toledo

    2010-08-01

    Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality related to human immunodeficiency virus (HIV infection, but in spite of this advance, HIV mutations decrease antiretroviral susceptibility, thus contributing to treatment failure in patients. Genotyping HIV-1 allows the selection of new drugs after initial drug failure. This study evaluated the genotypic profile of HIV-1 isolates from treated (drug-experienced patients in Paraná, Brazil. The prevalence of mutations in reverse transcriptase (RT and protease (PR genes were assessed. We analyzed 467 genotypes of patients with HIV-1 viral loads above 1,000 copies/mL. Mutations at HIV-1 RT and PR genes and previously used ART regimens were recorded. The most prevalent RT mutations were: 184V (68.31%, 215YF (51.6%, 103NS (46%, 41L (39.4%, 67N (38.54%, 210W (23.5%, 190ASE (23.2%, and 181C (17.4%. PR mutations were 90M (33.33%, 82ATFS (29%, 46I (26.8% and 54V (22.2%. The prevalence of mutations was in line with previous national and international reports, except to nonnucleoside analogue reverse transcriptase inhibitors related mutations, which were more prevalent in this study. Previous exposure to antiretroviral drugs was associated with genotypic resistance to specific drugs, leading to treatment failure in HIV patients.

  12. Phenotype-genotype correlations in patients with Wilson's disease.

    Science.gov (United States)

    Ferenci, Peter

    2014-05-01

    There is considerable phenotypic variation in Wilson's disease (WD). Some patients present with hepatic disease during the first decade of life and some with neurological degeneration in adolescence or adult life, with or without overt liver disease. Although the absence of neurologic disease in patients with liver disease in childhood or adolescence can be explained by the limited time exposure of the central nervous system to copper toxicity, it is surprising that late-onset neurologic WD can occur without any evidence of liver involvement. This huge variability in the clinical presentation of WD in general reflects our limited knowledge on the natural history of WD. Genetic association studies require the phenotype to be defined as accurately as possible.

  13. Detection of mumps virus genotype H in two previously vaccinated patients from Mexico City.

    Science.gov (United States)

    Del Valle, Alberto; García, Alí A; Barrón, Blanca L

    2016-06-01

    Infections caused by mumps virus (MuV) have been successfully prevented through vaccination; however, in recent years, an increasing number of mumps outbreaks have been reported within vaccinated populations. In this study, MuV was genotyped for the first time in Mexico. Saliva samples were obtained from two previously vaccinated patients in Mexico City who had developed parotitis. Viral isolation was carried out in Vero cells, and the SH and HN genes were amplified by RT-PCR. Amplicons were sequenced and compared to a set of reference sequences to identify the MuV genotype.

  14. Autoantibodies and hepatitis C virus genotypes in chronic hepatitis C patients in Estonia

    Institute of Scientific and Technical Information of China (English)

    Eva Zusinaite; Kaja Metsküla; Riina Salupere

    2005-01-01

    AIM: To determine the prevalence of several autoantibodies in chronic hepatitis C patients, and to find out whether the pattern of autoantibodies was associated with hepatitis C virus (HCV) genotypes.METHODS: Sera from 90 consecutive patients with chronic hepatitis C were investigated on the presence of anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA),anti-liver-kidney microsomal type 1 (LKMA1), anti-parietal cell (PCA), anti-thyroid microsomal (TMA), and anti-reticulin (ARA) autoantibodies. The autoantibodies were identified by indirect immunofluorescence. HCV genotypes were determined by a restriction fragment length polymorphism analysis of the amplified 5' noncoding genome region.RESULTS: Forty-six (51.1%) patients were positive for at least one autoantibody. Various antibodies were presented as follows: ANA in 13 (14.4%) patients, SMA in 39 (43.3%),TMA in 2 (2.2%), and ARA in 1 (1.1%) patients. In 9 cases,sera were positive for two autoantibodies (ANA and SMA).AMA, PCA and LKMA1 were not detected in the observed sera. HCV genotypes were distributed as follows: 1b in 66 (73.3%) patients, 3a in 18 (20.0%), and 2a in 6 (6.7%)patients.CONCLUSION: A high prevalence of ANA and SMA can be found in chronic hepatitis C patients. Autoantibodies are present at low titre (1: 10) in most of the cases. Distribution of the autoantibodies show no differences in the sex groups and between patients infected with different HCV genotypes.

  15. Genotypic linkages of gene segments of rotaviruses circulating in pediatric patients with acute gastroenteritis in Thailand.

    Science.gov (United States)

    Chaimongkol, Natthawan; Khamrin, Pattara; Malasao, Rungnapa; Thongprachum, Aksara; Ushijima, Hiroshi; Maneekarn, Niwat

    2012-10-01

    Rotavirus is a major cause of morbidity and mortality of infants and young children with diarrhea throughout the world. In Thailand, extensive studies of rotavirus infections have been reported continually and rotavirus diarrhea remains a common illness. To monitor the epidemiological situation of rotavirus in Chiang Mai, Thailand, surveillance of rotavirus circulating in pediatric patients was conducted. A total of 160 fecal specimens collected from children hospitalized with diarrhea were tested for rotaviruses groups A, B, and C by RT-PCR and their genotypes were identified by multiplex PCR and nucleotide sequencing. Group A rotavirus was detected at 29.4% but none of group B and C was found in this study. Molecular characterizations of G- and P-genotypes revealed three different G-P combinations, G1P[8] was the most predominant genotype with the prevalence of 72.3% followed by G2P[4] at 19.2%, and G3P[8] at 8.5%. Phylogenetic analyses of VP7 and VP4 genes of the representative strains detected in the present study, G1, G2, G3, and P[4] and P[8], respectively, revealed that G1 belonged to G1-Ic and G1-II, G2 belonged to G2-II, and G3 belonged to G3-III-S4 lineages while P[4] and P[8] were identified as P[4]-V and P[8]-III lineages. Analyses of VP6, NSP4, and NSP5 genes demonstrated that these representative strains belonged to genotypes I1 and I2, E1 and E2, and H1 and H2, respectively. Analyzing the association of G- and P-genotypes with I, E, H genotypes revealed unique patterns of genotypic linkage. The G1P[8] and G3P[8] were intimately linked with I1, E1, H1 genotypes and displayed the genetic features of G1-P[8]-I1-E1-H1 and G3-P[8]-I1-E1-H1, respectively, while G2P[4] was closely linked to I2, E2, H2 genotypes and showed the genetic pattern of G2-P[4]-I2-E2-H2. This study provides epidemiological information and insight into the genetic background of rotaviruses circulating in pediatric patients in Chiang Mai, Thailand.

  16. Is Period3 Genotype Associated With Sleep and Recovery in Patients With Disorders of Consciousness?

    Science.gov (United States)

    Bedini, Gloria; Bersano, Anna; Sebastiano, Davide Rossi; Sattin, Davide; Ciaraffa, Francesca; Tosetti, Valentina; Brenna, Greta; Franceschetti, Silvana; Ciusani, Emilio; Leonardi, Matilde; Vela-Gomez, Jesus; Boncoraglio, Giorgio B; Parati, Eugenio A

    2016-06-01

    Background Sleep evaluation is increasingly being used as prognostic tool in patients with disorders of consciousness, but, surprisingly, the role of Period3 (Per3) gene polymorphism has never been evaluated. Objective The aim of this study was to investigate the contribution of Per3 genotype on sleep quantity and consciousness recovery level in patients with disorders of consciousness (DOC). Methods In this observational study, we evaluated 71 patients with DOC classified as vegetative state/unresponsive wakefulness syndrome or minimally conscious state. Demographic and clinical data were collected and a standardised diagnostic workup, including a polysomnographic record, was applied. After informed consent provided by proxy, genomic DNA was obtained and Per3 polymorphism was analysed by polymerase chain reaction to identify 5/5, 4/5, or 4/4 genotype. Results Per3(5/5) genotype was found in 12.7% of our DOC patients. The median total Coma Recovery Scale-revised score in Per3(5/5) carriers was significantly higher than 4/4 genotype (10, range 5-16 vs 7, range 4-11; post hoc P = .036). Moreover, total sleep time seemed to be higher in 5/5 genotype (5/5, 221 minutes, range 88-515 minutes; 4/4, 151.5 minutes, range 36-477 minutes; and 4/5, 188 minutes, range 44-422 minutes). Conclusion For the first time we have shown a possible association between Per3 polymorphism and consciousness recovery level in DOC patients. Even though the exact molecular mechanism has not been defined, we speculate that its effect is mediated by higher total sleep time and slow wave sleep, which would improve the preservation of main cerebral connections.

  17. [Comparative study of the Candida albicans genotypes isolated from immunocompromised patients and health carriers].

    Science.gov (United States)

    Carnovale, S; Elias Costa, M R; Relloso, S; Negroni, R; Negroni, M B; Iovannitti, C

    2001-01-01

    The aim of this study is to compare Candida albicans strain genotype isolates from oral cavity of immunocompromised patients due to different immunologic impairments with apparently normal carriers. Four populations were studied: 1) HIV positive hospitalized patients, 2) HIV negative immunocompromised patients (leukemia, lymphoma, organ transplant recipients), 3) drug addicts prior to AIDS pandemia in Argentina, 4) apparently normal carriers. DNA extracted was digested with the enzyme Eco RI, electrophoresed, transferred to nitrocellulose membrane and hybridized with the 27A probe labelled with 32P. The comparison between the profiles obtained permitted the differentiation of 16 genotypes. The distribution of the strains led to the conclusion that: a) all the isolated strains from AIDS patients were closely related and distributed in only three genotypes (1, 3, 11); b) a major genetic relationship between the isolates from AIDS patients and HIV negative immunocompromised patients was observed; c) strains from carriers showed a minor genetic similarity with those obtained from AIDS patients; d) characteristic profiles belonging to any of the studied groups were not found; e) significant genomic changes have not been observed during the last twenty years.

  18. Viral hepatitis B, C infection and genotype distribution among cholangiocarcinoma patients in northeast Thailand.

    Science.gov (United States)

    Barusrux, Sahapat; Nanok, Chaiyachet; Puthisawas, Watcharapong; Pairojkul, Chawalit; Poovorawan, Yong

    2012-01-01

    The prevalence of HBV and HCV infection among 295 cholangiocarcinoma (CCA) patients in northeast Thailand was analyzed. Hepatitis B surface antigen (HBsAg) was detected in 8.8% (26/295 cases) and antibodies to HCV (anti-HCV) in 2.7% (8/295 cases) of CCA cases. Screening for HBV DNA was performed in 15 of 26 HBV seropositive cases and genotypes could be determined in all 15. HBV genotypes C and B were detected in 73.3% (11/15 cases) and 26.7% (4/15 cases), respectively. HCV RNA was detected in 87.5% (7/8 cases) of anti-HCV positive cases. Specifically, 57.1% (4/7 cases) were HCV genotype 1a and 42.9% (3/7 cases) were HCV genotype 3a. The prevalence of infection and genotype distribution of both HCV and HBV among CCA in northeast Thailand is comparable to that in the general population, suggesting that HCV and HBV infections are, if at all, not serious risk factors for CCA.

  19. [COMPREHENSIVE DIAGNOSTICS IN PATIENTS WITH GENOTYPE 47,XXY KLINEFELTER SYNDROME].

    Science.gov (United States)

    Akbarova, G A

    2016-01-01

    We undertook biochemical, hormonal, cytological analysis and sequencing CAG repetitions of androgen receptor gene in order to elucidate the cause of clinical polymorphism of Klinefelter syndrome. Elevated levels of LH (19.8 ± 4.2 E/l), FSH (22.7 ± 6.1 U/l), total cholesterol (6.8 ± 2.6 mmol/l), triglycerides (3.3 ± 1.0 mmol/l), and glucose (9.9 ± 3.8 mmol/l) suggested disturbances of lipid and carbohydrate metabolism. Two thirds of the patients had Klinfelter syndrome associated with mental retardation and psychic disorders. Patients with cleft palate and mental retardation and with psycho-social disorders had 45 and 43 CA G repetitions respectively, those without associations 38-40 repetitions. Increased frequency of CAG repetitions was directly proportional to the level ofpsychic development, social adaptation and professional activity but inversely proportional to the development of masculine sexual traits.

  20. Genotyping of Kell, Duffy, Kidd and RHD in patients with b Thalassemia

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    Castilho Lilian

    2000-01-01

    Full Text Available Determination of Rh, Kell, Duffy and Kidd phenotypes in addition to ABO is used to prevent the alloimmunization to red blood cells (RBCs antigens and as part of the antibody identification process in patients with beta Thalassemia. However, phenotyping in these patients can be time consuming and difficult to interpret. In these situations, it would be valuable to have an alternative to hemagglutination tests to determine the patient's antigen profile. We used PCR-RFLP to genotype such patients. DNA was prepared from 50 patients with beta Thalassemia who had been phenotyped by routine hemagglutination, and tested for Kell, Kidd, Duffy/GATA mutation by PCR-RFLP. RHD/non-D was analysed by PCR product size associated to RHD gene sequence in intron 4 and exon 10/3'UTR. The genotyping assays were performed without knowledge of phenotype results. For RHD/non-D, 47 were RhD+ and RHD+/RHCE+, and 3 were RhD- and RHD-/RHCE+. For Kell, 48 kk were K2K2 and 2 Kk were K1K2. For Duffy, of 44 samples that had normal GATA box, 8 Fy(a+b- were FYA/FYA, 15 Fy(a+b+ were FYB/FYB, and 19 Fy(a+b+ were FYA/FYB; of the other 4 samples 3 were FYA/FYB and heterozygous GATA mutation, and 1 Fy(a-b- was FYB/FYB, homozygous GATA mutation. Two samples phenotyped as Fy(a+b- that had normal GATA , presented the 265T/298A mutations and two samples phenotyped as Fy(a-b+ were genotyped was FYA/FYB.. For Kidd , 15 Jk(a+b were JKA/JKA, 12 Jk(a-b+ were JKB/JKB, and 20 Jk(a+b+ were JKA/JKB. Three samples phenotyped as JK(a+b+ were genotyped as JKB/JKB. Genotype is more accurate than phenotype for determination of blood groups in polytransfused patients with betaThalassemia. Genotyping in these patients can be helpful to select antigen-negative RBCs for transfusion.

  1. HFE mutations and hemochromatosis in Danish patients admitted for HFE genotyping

    DEFF Research Database (Denmark)

    Koefoed, P; Dalhoff, K; Dissing, J

    2002-01-01

    Analysis of the common C282Y and H63D mutations in the HFE gene is widely used to diagnose hereditary hemochromatosis (HH). The aim of this study was to evaluate the efficiency with which different hospitals and general practitioners select patients for HH genotype and to determine the distribution...... of HFE mutations in such patients. Nine hundred unrelated patients from Danish hospitals and general practitioners (group A) and 69 consecutive patients from a specialized liver unit (group B) were examined for HFE substitutions using multiplex real-time polymerase chain reaction. In group A we found 13...

  2. Molecular epidemiology of Brucella genotypes in patients at a major hospital in central Peru.

    Science.gov (United States)

    Nöckler, Karsten; Maves, Ryan; Cepeda, David; Draeger, Angelika; Mayer-Scholl, Anne; Chacaltana, Jesus; Castañeda, María; Espinosa, Benjamin; Castillo, Rosa; Hall, Eric; Al Dahouk, Sascha; Gilman, Robert H; Cabeza, Franco; Smits, Henk L

    2009-10-01

    The multiple-locus variable-number repeat analysis of 90 human Brucella melitensis isolates from a large urban area in central Peru revealed variations at 4 (Bruce07, Bruce09, Bruce18, and Bruce42) out of 16 loci investigated, of which 1 (Bruce42) also is used for species identification. Ten genotypes were identified, separated by the number of Bruce42 repeats into two groups that may have distinct phenotypic characteristics. Whereas genotypes with five or six Bruce42 repeats were cultured mainly from adult patients, genotypes with three Bruce42 repeats were isolated from children and young adolescents as well as from adults. In addition, the isolates with three Bruce42 repeats were obtained more often from patients with splenomegaly (P = 0.02) or hepatomegaly (P = 0.006). An annual variation in the diversity of genotypes was observed, possibly reflecting changes in sources of fresh dairy products, supply routes to city shops and markets, and the movement of infected dairy goat herds.

  3. Genotypic resistance tests in the management of the HIV-infected patient at virological failure.

    Science.gov (United States)

    Aceti, Antonio; Carosi, Giampiero

    2003-01-01

    Witness for the prosecution: The IAS-USA and Euro-Resistance Group HIV guidelines recommend the use of resistance testing for all patients experiencing treatment failure for whom therapy change is being considered. However, these assays suffer from several limitations (problems in sensitivity, specificity, complexity of interpretation, cost) and the results of the prospective studies evaluating genotype-guided treatment in HIV patients failing antiretroviral treatment are inconclusive and partially contrasting (virological benefit is short-term). On this basis, incorporating genotypic resistance assays into the clinical management of HIV patients experiencing first treatment failure is not a sufficiently evidence-based practice. Witness for the defence: Highly active antiretroviral therapy (HAART) has markedly improved the prognosis of HIV-infected patients by controlling HIV replication. However, HAART fails to control HIV replication in an increasing number of patients as a result of a complex array of causes. There is now substantial evidence that the emergence of drug resistance is a leading cause (as well as consequence) of antiretroviral therapy failure. Moreover, HIV drug resistance can be transmitted and this can favour initial treatment failure. Several retrospective and prospective studies have indicated that both genotypic and phenotypic HIV-1 drug resistance testing results are associated with, or predictive of, the virological outcome. As a consequence, international guidelines have soundly recommended the use of resistance testing to guide treatment choices after virological failure. The rationale and advantages of using such testing after first virological failure will be discussed.

  4. ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

    Directory of Open Access Journals (Sweden)

    Frankfort Suzanne V

    2006-09-01

    Full Text Available Abstract Amyloid β is an in vitro substrate for P-glycoprotein (P-gp, an efflux pump at the blood brain barrier (BBB. The Multi Drug Resistance (ABCB1 gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26 and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.

  5. CHC: A Robust P2P Overlay Network with Simple Routing and Small-World Features

    Directory of Open Access Journals (Sweden)

    Wenjun Xiao

    2011-08-01

    Full Text Available Almost all recent researches on P2P systems focus on howto build a highly usable P2P overlay network. Researchersinclude small routing table, short query path and goodrobustness into their design objectives of overlay topology. Inthis paper, we present a general group theory method anddefine a new Cayley graph. Based on this Cayley graph, wepropose a novel P2P overlay network called CHC, which hassimple routing (searching scheme and many other excellentproperties such as short query path, high clustering and goodrobustness because of its symmetry. The performance isevaluated by simulation to show that CHC possesses shorterquery path length and higher clustering and better robustnessthan several popular P2P overlay networks such as Chord andUlysses.

  6. BDNF genotype influence the efficacy of rTMS in stroke patients.

    Science.gov (United States)

    Uhm, Kyeong Eun; Kim, Yun-Hee; Yoon, Kyung Jae; Hwang, Jung Min; Chang, Won Hyuk

    2015-05-06

    Brain-derived neurotrophic factor (BDNF) genotype can influence neural response to repetitive transcranial magnetic stimulation (rTMS) in normal individuals. In this study we established personalized stimulus intensity of facilitatory rTMS according to BDNF genotype in stroke patients. Twenty-two chronic stroke patients were enrolled. All patients underwent three different sessions of rTMS over the ipsilesional M1 in randomized order with a washout period exceeding 24h: first condition, high-frequency rTMS with sub-threshold intensity; second condition, high-frequency rTMS with supra-threshold intensity; third condition, sham rTMS. Cortical excitability in the affected hemisphere was assessed with motor evoked potentials (MEPs) before and after stimulation. Data were analyzed according to BDNF genotype. Six [27.3%] and 16 [72.7%] participants were classified in the Val/Val group and Met allele group, respectively. In each group, significant increases were observed in the amplitude of MEPs after the stimulation in the first and second conditions (prTMS is used for the modulation of cortical excitability in patients with chronic stroke.

  7. Blood genotyping for improved outcomes in chronic transfusion patients: current and future perspectives

    Directory of Open Access Journals (Sweden)

    Kutner JM

    2014-09-01

    Full Text Available Jose Mauro Kutner,1 Mariza Mota,1 Fabiana Conti,1 Lilian Castilho1,2 1Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; 2Hemocentro Unicamp, Campinas, SP, Brazil Abstract: Blood transfusions are life sustaining in chronically transfused patients. However, certain complications, such as alloimmunization to red blood cells, can create challenges in the management of those patients. Routine phenotyping of blood recipients and the use of phenotype-matched blood units for transfusion have been useful to lower the occurrence of red cell alloantibodies in chronically transfused individuals. Nevertheless, extensive phenotyping is expensive, laborious, and cannot be performed in certain situations. The molecular understanding of blood groups has enabled the design of assays that may be used to better guide matched red blood cell transfusions. This review summarizes key findings related to red cell alloimmunization, the already identified and potential future benefits of blood group genotyping, and how molecular typing is being incorporated in the blood bank's routine to improve clinical and long-term outcomes in chronically transfused patients. Keywords: blood group genotyping, chronically transfused patients, platelet genotyping, RBC alloimmunization

  8. Identification of a natural intergenotypic recombinant hepatitis delta virus genotype 1 and 2 in Vietnamese HBsAg-positive patients.

    Science.gov (United States)

    Sy, B T; Nguyen, H M; Toan, N L; Song, L H; Tong, H V; Wolboldt, C; Binh, V Q; Kremsner, P G; Velavan, T P; Bock, C-T

    2015-01-01

    Hepatitis D virus (HDV) infection is acquired as a co- /superinfection of Hepatitis B virus (HBV) and can modulate the pathophysiology of chronic hepatitis B and related liver diseases including hepatocellular carcinoma. Among the eight distinct HDV genotypes reported, relatively few studies have attempted to investigate the prevalence of HDV mixed genotypes and RNA recombination of HDV. With a recorded prevalence of 10-20% HBV infection in Vietnam, this study investigated the HDV variability, HDV genotypes and HDV recombination among twenty-one HDV isolates in Vietnamese HBsAg-positive patients. HDV subgenomic and full-length genome sequences were obtained using newly established HDV-specific RT-PCR techniques. The nucleotide homology was observed from 74.6% to 99.4% among the investigated full-length genome of the HDV isolates. We observed HDV genotype 1 and HDV genotype 2 in the investigated Vietnamese patients. Although no HDV genotype mixtures were observed, we report here a newly identified recombinant of HDV genotypes (HDV 1 and HDV 2). The identified recombinant HDV isolate C03 revealed sequence homology to both HDV genotype 1 (nt1 to nt907) and HDV genotype 2 (nt908 to nt1675; HDAg coding region) with a breakpoint at nt908. Our findings demonstrate the prevalence of intergenotypic recombination between HDV genotypes 1 and 2 in a Vietnamese HBsAg-positive patient. Extended investigation on the distribution and prevalence of HDV, HDV mixed genotypes and recombinant HDV genotypes in a larger Vietnamese population offers vital insights into understanding of the micro-epidemiology of HDV and subsequent pathophysiology in chronic HBV- /HDV-related liver diseases.

  9. Genotype-phenotype correlation in Chinese patients with spinal and bulbar muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Wang Ni

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is an X-linked recessive motor neuron disease characterized by slowly progressive weakness and atrophy of proximal limbs and bulbar muscles. To assess the genotype-phenotype correlation in Chinese patients, we identified 155 patients with SBMA and retrospectively examined available data from laboratory tests and neurophysiological analyses. Correlations between genotype and phenotype were analyzed. There was an inverse correlation between the length of CAG repeats and age at first muscle weakness (p<0.0001. The serum creatine kinase level showed a significant inverse correlation with disease duration and the age at examination (p=0.019 and p=0.004, respectively. Unlike previous classification of motor- and sensory-dominant phenotypes, all findings of nerve conduction, except the amplitudes of median nerve compound motor action potential, were positively correlated to the length of CAG repeats. A significant decline in sensory nerve action potential amplitudes may assist differential diagnosis of SBMA.

  10. Sexual dysfunction and dissatisfaction in chronic hepatitis C patients

    Directory of Open Access Journals (Sweden)

    Bruno Cópio Fábregas

    2014-10-01

    Full Text Available Introduction The prevalence of sexual dysfunction (SD and dissatisfaction with sexual life (DSL in patients with chronic hepatitis C virus infection (CHC was jointly investigated via a thorough psychopathological analysis, which included dimensions such as fatigue, impulsiveness, psychiatric comorbidity, health-related quality of life (HRQL and sociodemographic and clinical characteristics. Methods Male and female CHC patients from an outpatient referral center were assessed using the Brief Fatigue Inventory, the Barrat Impulsiveness Scale, the Beck Depression Inventory (BDI, the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale (HAM-A, and the World Health Organization Quality of Life Scale-Brief Version (WHOQOL-BREF. Structured psychiatric interviews were performed according to the Mini-International Neuropsychiatric Interview. SD was assessed based on specific items in the BDI (item 21 and the HAM-A (item 12. DSL was assessed based on a specific question in the WHOQOL-BREF (item 21. Multivariate analysis was performed according to an ordinal linear regression model in which SD and DSL were considered as outcome variables. Results SD was reported by 60 (57.1% of the patients according to the results of the BDI and by 54 (51.4% of the patients according to the results of the HAM-A. SD was associated with older age, female gender, viral genotype 2 or 3, interferon-α use, impulsiveness, depressive symptoms, antidepressant and benzodiazepine use, and lower HRQL. DSL was reported by 34 (32.4% of the patients and was associated with depressive symptoms, anxiety symptoms, antidepressant use, and lower HRQL. Conclusions The prevalence of SD and DSL in CHC patients was high and was associated with factors, such as depressive symptoms and antidepressant use. Screening and managing these conditions represent significant steps toward improving medical assistance and the HRQL of CHC patients.

  11. Duffy blood group genotypes among malariaPlasmodiumvivax patients of Baoulch population in southeastern Iran

    Institute of Scientific and Technical Information of China (English)

    Ebrahim Miri-Moghaddam; Zakaria Bameri; Mehdi Mohamadi

    2014-01-01

    Objective:To determine the distribution ofDuffy blood group genotypes inBalouch population as a major ethnic group that living in a sub-tropical area in southEast ofIran.Methods:In this study, theDuffy blood groupFY phenotypes were determined using indirect anti-globulin technique and also genotype byPCR-RFLP in160 vivax malaria patients and160 control individuals.Results:The results showed that the most commonDuffy genotype wasFYA/FYB (46.6%) followed byFYA/FYA(15.3%),FYA/FYO(14.4%),FYB/FYO(11.9%),FYB/FYB(10%) and FYO/FYO(1.9%).In case individuals, frequency ofFYA,FYB andFYO alleles were0.471,0.431 and0.097, respectively compaired to0.444,0.353 and0.203, respectively in control(non-infected) group.Conclusions:This data provide evidence that individuals with theFYA/FYB genotype have higher susceptibility to malaria and there are significant associations betweenDuffy blood group variants and susceptibility or resistance to vivax malaria.

  12. Cost-effectiveness of Cyp2d6 genotyping in older depressed patients, starting with nortriptyline therapy

    NARCIS (Netherlands)

    Berm, E.J.; Gout-Zwart, J.J.; Luttjeboer, J.; Maring, J.G.; Wilffert, B.; Postma, M.J.

    2015-01-01

    Objectives: Genotyping for the cytochrome P450-2D6 has the potency to predict differences in metabolism of nortriptyline. This information could optimize treatment. We explored if possible benefits could outweigh genotyping costs for Dutch depressed patients in clinical psychiatry. Methods: First, a

  13. Evaluation of glycoprotein B genotypes and load of CMV infecting blood leukocytes on prognosis of AIDS patients

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    Aldo Albuquerque Cunha

    2011-04-01

    Full Text Available BACKGROUND: Cytomegalovirus (CMV remains an important pathogen to immunocompromised patients even in the era of HAART. The present study aimed at evaluating the influence of CMV viral load and its gB genotypes on AIDS patients' outcome. METHODS: Blood samples of 101 AIDS patients were collected and tested for HIV load, CD4 - cell count and opportunistic pathogens, including CMV. Semi-nested PCRs were run to detect CMV genome and in the positive samples, gB genotyping and CMV load were established using enzymatic restriction and real time PCR, respectively. All patients were clinically followed for four years. RESULTS: In thirty patients (31% CMV was detected and all fatal cases (n = 5 occurred in this group of patients (p = 0.007, but only two patients had CMV disease (1.9%. However, viral load was not statistically associated with any analyzed parameter. The most frequently observed CMV genotype was gB2 (45.16% followed by gB3 (35.48%. gB2 genotype was more frequently found in patients with CD4-cell counts under 200 cells/mm³ (p = 0.0017, and almost all fatal cases (80% had gB2 genotype. CONCLUSIONS: Our study suggests that CMV and its polymorphisms in biologically relevant genes, such as the gB encoding ORF, may still influence the prognosis and outcome of AIDS patients. The gB2 genotype was associated to patient's bad outcome.

  14. Patients with Haemoglobinopathies and Chronic Hepatitis C: A Real Difficult to Treat Population in 2016?

    Science.gov (United States)

    Zachou, Kalliopi; Arvaniti, Pinelopi; Gatselis, Nikolaos K; Azariadis, Kalliopi; Papadamou, Georgia; Rigopoulou, Eirini; Dalekos, George N

    2017-01-01

    In the past, patients with haemoglobinopathies were at high risk of acquiring hepatitis C virus (HCV) due to multiple transfusions before HCV screening. In these patients, the coexistence of haemochromatosis and chronic hepatitis C (CHC) often leads to more severe liver disease. We assessed the HCV prevalence, clinical characteristics and outcome in this setting with particular attention to the response to treatment including therapies with the new direct acting antivirals (DAAs). The medical records of 81 consecutive patients followed the last 15 years were reviewed retrospectively. 43/81 (53%) patients were anti-HCV positive including 31/43 (72.1%) with CHC (HCV-RNA positive; age 25±7 years; 45.2% with genotype 1b; 19.4% cirrhotics; baseline ferritin 887 ng/ml; range: 81-10.820). Thirty patients received IFN-based therapy with or without ribavirin with sustained virological response (SVR) in 14/30 (46.7%). Eleven patients (9 non-responders to IFN-based therapies, one in relapse and one naïve) received treatment with DAAs (SVR: 100%). 3/11 patients increased their transfusion needs while 1/11 reported mild arthralgias. No drug-drug interactions between DAAs and chelation agents were observed as attested by the stability of ferritin levels during treatment. More than 1/3 of patients with haemoglobinopathies suffered from CHC. Response rates to IFN-based treatment seem to be similar to other patients with CHC, while most importantly, treatment with DAAs was excellent and safe even in difficult to treat patients (most null responders with severe fibrosis) suggesting that this group of HCV patients should no longer be regarded as a difficult to treat.

  15. PATIENTS WITH HAEMOGLOBINOPATHIES AND CHRONIC HEPATITIS C: A REALLY DIFFICULT TO TREAT POPULATION IN 2016?

    Directory of Open Access Journals (Sweden)

    Kalliopi Zachou

    2017-01-01

    Full Text Available Background & objectives: In the past, patients with haemoglobinopathies were at high risk for acquiring hepatitis C virus (HCV due to multiple transfusions before HCV screening. In these patients the coexistence of haemochromatosis and chronic hepatitis C (CHC often leads to more severe liver disease. We assessed the HCV prevalence, clinical characteristics and outcome in this setting with particular attention to the response to treatment including therapies with the new direct acting antivirals (DAAs. Methods: The medical records of 81 consecutive patients followed the last 15 years were reviewed retrospectively. Results: 43/81 (53% patients were anti-HCV positive including 31/43 (72.1% with CHC (HCV-RNA positive; age 25±7 years; 45.2% with genotype 1b; 19.4% cirrhotics; baseline ferritin 887 ng/ml; range: 81-10.820.  Thirty patients received IFN-based therapy with or without ribavirin with sustained virological response (SVR in 14/30 (46.7%.   Eleven patients (9 non-responders to IFN-based therapies, 1 relapser and 1 naïve received treatment with DAAs (SVR: 100%. 3/11 patients increased their transfusion needs while 1/11 reported mild arthralgias. No drug-drug interactions between DAAs and chelation agents were observed as attested by the stability of ferritin levels during treatment.  Conclusions: More than 1/3 of patients with haemoglobinopathies suffered from CHC. Response rates to antiviral treatment seem to be similar to other patients with CHC, while treatment with DAAs was very effective and safe even in difficult to treat patients (most null responders with severe fibrosis suggesting that this group of HCV patients should no longer be regarded as a difficult to treat.

  16. Mutations in the gene region of hepatitis B virus genotype in Turkish patients

    Indian Academy of Sciences (India)

    Mehmet Özaslan; Ersan Özaslan; Arzu Barsgan; Mehmet Koruk

    2007-12-01

    The gene region of the hepatitis B virus (HBV) is responsible for the expression of surface antigens and includes the ‘a’-determinant region. Thus, mutation(s) in this region would afford HBV variants a distinct survival advantage, permitting the mutant virus to escape from the immune system. The aim of this study was to search for mutations of the gene region in different patient groups infected with genotype variants of HBV, and to analyse the biological significance of these mutations. Moreover, we investigated gene mutation inductance among family members. Forty HBV-DNA-positive patients were determined among 132 hepatitis B surface antigen (HbsAg) carriers by the first stage of seminested PCR. Genotypes and subtypes were established by sequencing of the amplified S gene regions. Variants were compared with original sequences of these serotypes, and mutations were identified. All variants were designated as genotype and subtype ayw3. Ten kinds of point mutations were identified within the region. The highest rates of mutation were found in chronic hepatitis patients and their family members. The amino acid mutations 125 (M → T) and 127 (T → P) were found on the first loop of ‘a’-determinant. The other consequence was mutation inductance in a family member. We found some mutations in the S gene region known to be stable and observed that some of these mutations affected gene expression.

  17. Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

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    Stella M Martinez

    Full Text Available BACKGROUND/AIMS: Liver stiffness (LS measurement by means of transient elastography (TE is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC. METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7% and 192 untreated patients (37.3% were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001. The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively. Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR. In multivariate analysis, high baseline LS (P<0.0001 and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS and suggests an improvement in liver damage.

  18. Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

    Science.gov (United States)

    Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

    2012-01-01

    Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

  19. Clusters of patients with candidaemia due to genotypes of Candida albicans and Candida parapsilosis: differences in frequency between hospitals.

    Science.gov (United States)

    Marcos-Zambrano, L J; Escribano, P; Sanguinetti, M; Gómez G de la Pedrosa, E; De Carolis, E; Vella, A; Cantón, R; Bouza, E; Guinea, J

    2015-07-01

    The presence of clusters (identical genotypes infecting different patients) suggests patient-to-patient transmission or a common source for strains. We report the results of a genotyping study based on microsatellite markers of Candida albicans (n = 179) and Candida parapsilosis (n = 76) causing candidaemia, to assess and compare the percentage of patients grouped in clusters during the study period (January 2010 to December 2012). The study was performed in two large tertiary hospitals in Madrid, Spain. We detected 145 C. albicans genotypes (21 in clusters) and 63 C. parapsilosis genotypes (seven in clusters). Clusters involved two to seven patients each. Most of the clusters in the two centres involved two patients for both species, but the number of patients included in each cluster differed between hospitals. Considering both species, the percentage of patients per cluster ranged from 19% to 38% (p albicans and C. parapsilosis genotypes causing candidaemia differed between hospitals, suggesting differences in strain transmission. Occasionally, the same genotypes were found in patients admitted to different hospitals located in the same city.

  20. High proportion of hepatitis C virus genotypes 1 and 3 in a large cohort of patients from Southern Brazil

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    Cláudia Maria Dornelles da Silva

    2007-11-01

    Full Text Available Hepatitis C virus (HCV isolates have been divided into six genotypes (1 to 6. The duration of hepatitis C standard treatment is 48 weeks for patients infected with HCV genotype 1 vs 24 weeks for those infected with genotypes 2 and 3. A total of 1544 HCV isolates from chronic patients living in the southern Brazilian states of Rio Grande do Sul (RS, n = 627 and Santa Catarina (SC, n = 917 were genotyped by restriction fragment length polymorphism (RFLP of polymerase chain reaction (PCR products. In RS, 338 (53.9%; 95% CI 50.0 - 57.8%, 34 (5.4%; 95% CI 3.8 - 7.4% and, 255 (40.7%; 95% CI 36.9 - 44.6% samples were from genotypes 1, 2, and 3, respectively. In SC, 468 (51%; 95% CI 47.8 - 54.2%, 26 (2.9%; 95% CI 1.9 - 4.1% and, 423 (46.1%; 95% CI 42.9 - 49.3% samples were from genotypes 1, 2, and 3, respectively. Genotyping results were confirmed by direct nucleotide sequencing of PCR products derived from 68 samples, without any discrepancy between PCR-RFLP and nucleotide sequencing methods. In conclusion, almost half of the hepatitis C patients from South of Brazil are infected by genotypes 2 and 3 and, these results have important consequential therapeutic implications as they can be treated for only 24 weeks, not 48.

  1. Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2% of the Scand......The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in approximately 2...

  2. Genotyping Klebsiella pneumoniae isolated from hepatic abscesses in three patients from Bogota, Colombia

    Directory of Open Access Journals (Sweden)

    Dora I. Ríos

    2013-01-01

    Full Text Available Pyogenic liver abscess caused by Klebsiella pneumoniae represents an ever increasing entity which has mainly been described as occurring in Asia, even though, on a smaller scale, cases are being more frequently described from the USA and Europe, 13% overall mortality being reached worldwide. Affected patients are severely sick, suffering from fever, sweating, having increased acute phase reactants and risk factors such as Diabetes Mellitus, alcoholism and the inherent characteristics of the bacteria causing the disease. Objective: in this work we used a Multilocus Sequencing Typing (MLST, a nucleotide sequence-based method in order to characterize the genetic relationships among bacterial isolates. Materials and methods: the report is focused on three cases involving patients suffering from pyogenic liver abscess caused by Klebsiella pneumoniae in two hospitals in Bogota, Colombia, where phenotyping and hypermucoviscosity studies were carried out, as well as the genotyping of cultured Klebsiella isolates. Reults: it was found that the isolated microorganism in cases I and II corresponded to the same K. pneumoniae strain, having 100% sequence identity for the 5 genes being studied while the strain in Case III was genotypically different. Conclusion: it is important to carry out multidisciplinary studies allowing all pyogenic liver abscess cases reported in Colombia to be complied to ascertain the frequency of microorganisms causing this pathology in our country, as well as a genotyping study of different K. pneumoniae strains to compare them and confirm clonal and pathogenicity relationships through housekeeping gene analysis.

  3. Genotypes of Mycobacterium tuberculosis in patients at risk of drug resistance in Bolivia.

    Science.gov (United States)

    Monteserin, Johana; Camacho, Mirtha; Barrera, Lucía; Palomino, Juan Carlos; Ritacco, Viviana; Martin, Anandi

    2013-07-01

    Bolivia ranks among the 10 Latin American countries with the highest rates of tuberculosis (TB) and multidrug resistant (MDR) TB. In view of this, and of the lacking information on the population structure of Mycobacterium tuberculosis in the country, we explored genotype associations with drug resistance and clustering by analyzing isolates collected in 2010 from 100 consecutive TB patients at risk of drug resistance in seven of the nine departments in which Bolivia is divided. Fourteen isolates were MDR, 29 had other drug resistance profiles, and 57 were pansusceptible. Spoligotype family distribution was: Haarlem 39.4%, LAM 26.3%, T 22.2%, S 2.0%, X 1.0%, orphan 9.1%, with very low intra-family diversity and absence of Beijing genotypes. We found 66 different MIRU-VNTR patterns; the most frequent corresponded to Multiple Locus Variable Analysis (MLVA) MtbC15 patterns 860, 372 and 873. Twelve clusters, each with identical MIRU-VNTR and spoligotypes, gathered 35 patients. We found no association of genotype with drug resistant or MDR-TB. Clustering associated with SIT 50 and the H3 subfamily to which it belongs (pBolivia. However, results should be taken cautiously because the sample is small and includes a particular subset of M. tuberculosis population. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. HFE Genotyping in Patients with Elevated Serum Iron Indices and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Andreia Silva Evangelista

    2015-01-01

    Full Text Available Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS > 45%, and serum ferritin (SF > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n=16 were the HFE hereditary hemochromatosis (HFE-HH group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n=92. Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 μg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population.

  5. KIR-HLA genotypes in HIV-infected patients lacking immunological recovery despite effective antiretroviral therapy.

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    Alessandro Soria

    Full Text Available BACKGROUND: In HIV-infected individuals, mechanisms underlying unsatisfactory immune recovery during effective combination antiretroviral therapy (cART have yet to be fully understood. We investigated whether polymorphism of genes encoding immune-regulating molecules, such as killer immunoglobulin-like receptors (KIR and their ligands class I human leukocyte antigen (HLA, could influence immunological response to cART. METHODS: KIR and HLA frequencies were analyzed in 154 HIV-infected and cART-treated patients with undetectable viral load divided into two groups: 'immunological non responders' (INR, N = 50, CD4(+ T-cell count 350/mm(3. Molecular KIR were typed using polymerase chain reaction-based genotyping. Comparisons were adjusted for baseline patient characteristics. RESULTS: The frequency of KIR2DL3 allele was significantly higher in FR than in INR (83.7% vs. 62%, P = 0.005. The functional compound genotype HLA-C1(+/KIR2DL3(+, even at multivariable analysis, when adjusted for nadir CD4(+ T-cell count, was associated with reduced risk of INR status: odds ratio (95% Confidence Intervals 0.34 (0.13-0.88, P = 0.03. CONCLUSIONS: Reduced presence of the inhibitory KIR2DL3 genotype detected in INR might provoke an imbalance in NK function, possibly leading to increased immune activation, impaired killing of latently infected cells, and higher proviral burden. These factors would hinder full immune recovery during therapy.

  6. Isolation and characterization of new Leptospira genotypes from patients in Mayotte (Indian Ocean.

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    Pascale Bourhy

    Full Text Available BACKGROUND: Leptospirosis has been implicated as a severe and fatal form of disease in Mayotte, a French-administrated territory located in the Comoros archipelago (southwestern Indian Ocean. To date, Leptospira isolates have never been isolated in this endemic region. METHODS AND FINDINGS: Leptospires were isolated from blood samples from 22 patients with febrile illness during a 17-month period after a PCR-based screening test was positive. Strains were typed using hyper-immune antisera raised against the major Leptospira serogroups: 20 of 22 clinical isolates were assigned to serogroup Mini; the other two strains belonged to serogroups Grippotyphosa and Pyrogenes, respectively. These isolates were further characterized using partial sequencing of 16S rRNA and ligB gene, Multi Locus VNTR Analysis (MLVA, and pulsed field gel electrophoresis (PFGE. Of the 22 isolates, 14 were L. borgpetersenii strains, 7 L. kirschneri strains, and 1, belonging to serogoup Pyrogenes, was L. interrogans. Results of the genotyping methods were consistent. MLVA defined five genotypes, whereas PFGE allowed the recognition of additional subgroups within the genotypes. PFGE fingerprint patterns of clinical strains did not match any of the patterns in the reference strains belonging to the same serogroup, suggesting that the strains were novel serovars. CONCLUSIONS: Preliminary PCR screening of blood specimen allowed a high isolation frequency of leptospires among patients with febrile illness. Typing of leptospiral isolates showed that causative agents of leptospirosis in Mayotte have unique molecular features.

  7. Cytokine genotype distribution in patients with periodontal disease and rheumatoid arthritis or diabetes mellitus.

    Science.gov (United States)

    Crincoli, V; Ballini, A; Fatone, L; Di Bisceglie, M B; Nardi, G M; Grassi, F R

    2016-01-01

    The association between oral and systemic health has highlighted the importance of periodontal health and treatment, with the consequence that dental assessment and attention to oral hygiene have assumed an increasingly important part in the clinical management of patients with diabetes mellitus and rheumatoid arthritis. The aim of this work was to assess genotype frequencies in polymorphisms of genes of IL-1α-889 and IL-1β-511 in a case-controlled study population of patients affected by periodontal disease and rheumatoid arthritis or diabetes mellitus.

  8. Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Farah; Bokharaei; Salim; Hossein; Keyvani; Afsaneh; Amiri; Fatemeh; Jahanbakhsh; Sef; idi; Ramin; Shakeri; Farhad; Zamani

    2010-01-01

    AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications...

  9. Сost-effectiveness of the second wave of protease inhibitors in the treatment of chronic hepatitis C (genotype 1 in patients not previously treated with antiviral drugs, and for relapsed disease

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2016-01-01

    Full Text Available The protease inhibitors (PI actively using for the treatment of chronic hepatitis C (CHC.The aim of this analysis was to evaluate the cost-effectiveness of narlaprevir and simeprevir in the CHC (genotype 1 therapy in treatment-naïve patients and relapses.Material and methods. Analysis of the cost-effectiveness of simeprevir and narlaprevir was conducted from the perspective of the health care system and base on QUEST-1, QUEST-2, ASPIRE and PIONEER clinical trials. The relative risk of achieving SVR 24 compared to the peg-INF + RBV therapy was used in the model. Treatment discontinuation in patients receiving narlaprevir assumed in the absence of a SVR after 12 weeks and in patients receiving simeprevir in the SVR absence after 4 weeks. The cost of narlaprevir was calculate based on estimated registration price in case of EDL (essential pharmaceutical list approved by MOH inclusion, including VAT (10% and 10% as trade margin. Costs of other antiviral products were in line with the results of 2015 average auctions prices.Results. In the base case costs on antiviral products with narlaprevir as first-line therapy are lower compared with simeprevir by 12,2% (950,6 and 1083,0 thousand RUR, respectively, and the cost per patient with SVR 24 by 7,8%. In patients group after relapse costs on antiviral products with narlaprevir as first-line therapy will decrease compared with simeprevir by 4,3% (971,3 and 1014,7 thousand RUR, respectively, and the cost per patient with SVR 24 by 25,0%. The sensitivity analysis demonstrated a high reliability of obtained results. Thus, assuming equal clinical effectiveness of narlaprevir and simeprevir, costs of treatment naive patients will be 10.6% lower for narlaprevir group compared to simeprevir group (953,0 and 1066,0 thousand rur, respectively, and by 12,9% for the treatment of relapses (957,9 and 1100,0 thousand RUR, respectively.Conclusions. With comparable clinical efficacy and

  10. Revisiting the stopping rule for hepatitis C genotype 1 patients treated with peginterferon plus ribavirin.

    Directory of Open Access Journals (Sweden)

    Ming-Lung Yu

    Full Text Available BACKGROUND: The current stopping rule for peginterferon/ribavirin therapy in hepatitis C virus genotype-1 (HCV-1 patients is based on an early virological response (EVR, defined as >2 log(10 viral reduction at treatment week 12. We aimed to explore rapid stopping rules at week 4. METHODS: We randomly allocated 528 HCV-1 patients into training and validation sets (at a 1∶2 ratio. The interleukin-28B rs8099917 genotypes and on-treatment virological responses were evaluated to determine the negative predictive value (NPV for achieving a sustained virological response (SVR, defined as undetectable HCV RNA 24 weeks after end-of-treatment. The study was approved by the ethics committees of the participating hospitals. All of the patients gave written informed consent before enrollment. RESULTS: A poor week 4 response (W4R, defined as a HCV RNA reduction of 10,000 IU/mL with interleukin-28B non-TT genotype, had the highest NPV (95%. In the complete sample, poor W4R could identify 43.4% (59/136 of the non-responders, with an NPV of 95% and a false negative rate of only 0.8% (3/396. The multivariate analysis revealed that a poor W4R was the most important negative predictor (odds ratio/95% confidence intervals: 49.01/13.70-175.37, followed by the lack of an EVR. In addition to HCV RNA10,000 IU/mL/non-TT genotype helped identifying an additional one-third of non-SVR patients at W4.Using the strategy of sequential rapid stopping rule strategy could identify 53.7% (73/136 of the non-responders (43.4% at week 4 and an addition 11.3% at week 12, as compared to 40.4% for the classical week-12 early stopping rule. CONCLUSIONS: Sequential rapid stopping rules using on-treatment virological responses and interleukin-28B genotype can rapidly identify additional peginterferon/ribavirin non-responders.

  11. Cost-effectiveness analysis of therapeutic options for chronic hepatitis C genotype 3 infected patients.

    Science.gov (United States)

    Gimeno-Ballester, Vicente; Mar, Javier; O'Leary, Aisling; Adams, Róisín; San Miguel, Ramón

    2017-01-01

    This study provides a cost-effectiveness analysis of therapeutic strategies for chronic hepatitis C genotype 3 infected patients in Spain. A Markov model was designed to simulate the progression in a cohort of patients aged 50 years over a lifetime horizon. Sofosbuvir (SOF) plus peginterferon and ribavirin for 12 weeks was a cost-effective option when compared to standard of care (SoC) in the treatment of both 'moderate fibrosis' and 'cirrhotic' patients. Incremental cost-effectiveness ratios were €35,276/QALY and €18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens versus SoC were over the threshold limit considered, at €56,178/QALY and €77,378/QALY for 'moderate fibrosis' and 'cirrhotic' patients respectively. Addition of SOF to IFN-based regimens for genotype 3 was cost-effective for both 'moderate fibrosis' and 'cirrhotic' patients. IFN-free options including SOF and DCV association required price reductions lower than the list prices to be considered cost-effective.

  12. HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: a nationwide cohort study

    DEFF Research Database (Denmark)

    Krarup, Henrik Bygum; Andersen, Stig; Madsen, Poul Henning;

    2011-01-01

    To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....

  13. HBeAg and not genotypes predicts viral load in patients with hepatitis B in Denmark: A nationwide cohort study

    DEFF Research Database (Denmark)

    Krarup, Henrik; Andersen, Stig; Madsen, Poul Henning;

    2011-01-01

    To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe).......To explore the influence of HBV genotype on viral load in patients with HBV infection, and to investigate the relation to gender, age and country of origin or antibodies against hepatitis Be antigen (anti-HBe)....

  14. Hepatitis B virus genotype G: prevalence and impact in patients co-infected with human immunodeficiency virus.

    Science.gov (United States)

    Dao, Doan Y; Balko, Jody; Attar, Nahid; Neak, Enayet; Yuan, He-Jun; Lee, William M; Jain, Mamta K

    2011-09-01

    Relatively little is known about the role of hepatitis B virus (HBV) genotype G (HBV/G) in patients co-infected with human immunodeficiency virus (HIV) and HBV. This study examined the prevalence and association of HBV/G to liver fibrosis in co-infected patients. HBV genotypes were determined by direct sequencing of the HBV surface gene or Trugene® HBV 1.0 assay in 133 patients infected with HIV/HBV. Quantitative testing of HBV-DNA, HBeAg, and anti-HBe were performed using the Versant® HBV 3.0 (for DNA) and the ADVIA®Centaur assay. The non-invasive biomarkers Fib-4 and APRI were used to assess fibrosis stage. Genotype A was present in 103/133 (77%) of the cohort, genotype G in 18/133 (14%) with genotypes D in 8/133, (6%), F 2/133 (1.5%), and H 2/133 (1.5%). Genotype G was associated with hepatitis B e antigen-positivity and high HBV-DNA levels. Additionally, HBV/G (OR 8.25, 95% CI 2.3-29.6, P = 0.0012) was associated with advanced fibrosis score using Fib-4, whereas, being black was not (OR 0.19, 95% CI 0.05-0.07, P = 0.01). HBV/G in this population exhibited a different phenotype than expected for pure G genotypes raising the question of recombination or mixed infections. The frequent finding of HBV/G in co-infected patients and its association with more advanced fibrosis, suggests that this genotype leads to more rapid liver disease progression. Further studies are needed to understand why this genotype occurs more frequently and what impact it has on liver disease progression in patients with HBV/HIV.

  15. Adipocytokine Imbalance and Ghrelin in the Development of Insulin Resistance in Patients with Chronic Hepatitis C

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    Larisa Tkachenko

    2016-03-01

    Full Text Available The aim of this study was to determine the role of the most informative indicators of adipocytokine status and ghrelin in insulin resistance (IR formation in chronic hepatitis C (CHC patients at different stages of liver fibrosis (LF. Materials and Methods: This study included 205 CHC patients with HCV genotypes 1 and 3. A comparative analysis of the laboratory parameters was carried out in a group of patients with IR (n=110 and without IR (n=95 and in patients depending on the stage of LF. The serum levels of adipocytokines and ghrelin were determined using Bachem Group (USA and Immundiagnostik AG (Germany test systems with microplate reader Elx800 (FinBio, Finland. Diagnosis and assessment of the degree of fibrosis was performed by liver biopsy, liver elastometry and calculation test FibroTest. Results: Obtained data allow us to regard the decreased secretion of ghrelin, and increased production of leptin, resistin and TNF-α as a component involved in the formation of IR in CHC patients.

  16. Neutralizing antibodies in patients with chronic hepatitis C, genotype 1, against a panel of genotype 1 culture viruses: lack of correlation to treatment outcome.

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    Jannie Pedersen

    Full Text Available The correlation of neutralizing antibodies to treatment outcome in patients with chronic hepatitis C virus (HCV infection has not been established. The aim of this study was to determine whether neutralizing antibodies could be used as an outcome predictor in patients with chronic HCV, genotype 1, infection treated with pegylated interferon-α and ribavirin. Thirty-nine patients with chronic hepatitis C, genotype 1a or 1b, with either sustained virologic response (n = 23 or non-sustained virologic response (n = 16 were enrolled. Samples taken prior to treatment were tested for their ability to neutralize 6 different HCV genotype 1 cell culture recombinants (1a: H77/JFH1, TN/JFH1, DH6/JFH1; 1b: J4/JFH1, DH1/JFH1, DH5/JFH1. The results were expressed as the highest dilution yielding 50% neutralization (NAb50-titer. We observed no genotype or subtype specific differences in NAb50-titers between patients with chronic HCV infection with and without sustained virologic response when tested against any of the included culture viruses. However, NAb50-titers varied significantly with a mean reciprocal NAb50-titer of 800 (range: 100-6400 against DH6/JFH1 compared to a mean NAb50-titer of 50 (range: <50-400 against all other included isolates. Subsequent studies demonstrated that the efficient neutralization of DH6/JFH1 could be linked to engineered adaptive mutations in the envelope-2 protein. In analysis of envelope 1 and 2 sequences of HCV, recovered from a subset of patients, we observed no apparent link between relatedness of patient sequences with culture viruses used and the corresponding neutralization results. In conclusion, pre-treatment levels of neutralizing antibodies against HCV genotype 1 isolates could not predict treatment outcome in patients with chronic HCV infection. High neutralization susceptibility of DH6/JFH1 could be correlated with adaptive envelope mutations previously highlighted as important for neutralization. Our

  17. Prevalence of hepatitis C virus (HCV infection and HCV genotypes of hemodialysis patients in Salvador, Northeastern Brazil

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    Silva L.K.

    2006-01-01

    Full Text Available Hepatitis C virus (HCV infection has been identified as the major cause of chronic liver disease among patients on chronic hemodialysis (HD, despite the important reduction in risks obtained by testing candidate blood donors for anti-HCV antibodies and the use of recombinant erythropoietin to treat anemia. A cross-sectional study was performed to estimate the prevalence of HCV infection and genotypes among HD patients in Salvador, Northeastern Brazil. Anti-HCV seroprevalence was determined by ELISA in 1243 HD patients from all ten different dialysis centers of the city. HCV infection was confirmed by RT-PCR and genotyping was performed by restriction fragment length polymorphism. Anti-HCV seroprevalence among HD patients was 10.5% (95% CI: 8.8-12.3 (Murex anti-HCV, Abbott Murex, Chicago, IL, USA. Blood samples for qualitative HCV detection and genotyping were collected from 125/130 seropositive HD patients (96.2%. HCV-RNA was detected in 92/125 (73.6% of the anti-HCV-positive patients. HCV genotype 1 (77.9% was the most prevalent, followed by genotype 3 (10.5% and genotype 2 (4.6%. Mixed infections of genotypes 1 and 3 were found in 7.0% of the total number of patients. The present results indicate a significant decrease in anti-HCV prevalence from 23.8% detected in a study carried out in 1994 to 10.5% in the present study. The HCV genotype distribution was closely similar to that observed in other hemodialysis populations in Brazil, in local candidate blood donors and in other groups at risk of transfusion-transmitted infection.

  18. Genotype of cytochrome-450 2C9 in patients with tuberculosis

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    Kresyun V.I.

    2013-06-01

    Full Text Available The aim of present work was to investigate CYP2С9 polymorphism in the south of Ukraine in TB-patients and comparing with the same data of control group by the example of Odessa region. Gene CYP2С9 polymorphism was studied with the help of PCR (polymerase chain reaction and endonuclease analysis. The blood samples were obtained from patients with new cases of pulmonary TB from Odessa regional antituberculous dispensary and healthy donors in Odessa district station of blood transfusion in the year 2010-12. According to genotype of CYP2C9 of 55 TB-patients, 67,3% persons were the carriers of homozygote wild gene CYP2C9*1/*1, 21,8 and 3,6% - heterozygote genes CYP2C9*1/*2 and CYP2C9*1/*3. Only 7,2% individuals belonged to carriers of slow metabolizers genotype - CYP2C9*2/*2, *2/*3, *3/*3. In general, the mutated alleles CYP2C9*2 and CYP2C9*3 in TB-males were observed by 1,8 times more frequently than among healthy donors of the same gender. TB-patients older than 30 years more frequently had mutated allele CYP2C9*2, almost by 3 times than individuals from control group.

  19. Phenotype-Genotype Analysis of Chinese Patients with Early-Onset LMNA-Related Muscular Dystrophy.

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    Dandan Tan

    Full Text Available This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA-related muscular dystrophy (MD. The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293 cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD. Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

  20. Identification and isolation of Genotype-I Japanese Encephalitis virus from encephalitis patients

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    Gao Xiaoyan

    2010-11-01

    Full Text Available Abstract Historically, Japanese Encephalitis virus (JEV genotype III (GIII has been responsible for human diseases. In recent years, JEV genotype I (GI has been isolated from mosquitoes collected in numerous countries, but has not been isolated from patients with encephalitis. In this study, we report recovery of JEV GI live virus and identification of JEV GI RNA from cerebrospinal fluid (CSF of encephalitis patients in JE endemic areas of China. Whole-genome sequencing and molecular phylogenetic analysis of the JEV isolate from the CSF samples was performed. The isolate in this study is highly similar to other JEV GI strains which isolated from mosquitoes at both the nucleotide and deduced amino acid levels. Phylogenetic analysis based on the genomic sequence showed that the isolate belongs to JEV GI, which is consistent with the phylogenetic analysis based on the pre-membrane (PrM and Glycoprotein genes. As a conclusion, this is the first time to isolate JEV GI strain from CSF samples of encephalitis patients, so continuous survey and evaluate the infectivity and pathogenecity of JEV GI strains are necessary, especially for the JEV GI strains from encephalitis patients. With respect to the latter, because all current JEV vaccines (live and inactivated are derived from JEV GIII strains, future studies should be aimed at investigating and monitoring cross-protection of the human JEV GI isolates against widely used JEV vaccines.

  1. Hepatitis C virus seroprevalence and genotypes in patients with diffuse connective tissue diseases and spondyloarthropathies

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    Barbosa V.S.

    2005-01-01

    Full Text Available Many extrahepatic manifestations, including rheumatic diseases, have been reported to be associated with hepatitis C virus (HCV infection. In order to investigate the prevalence of HCV infection among patients with rheumatic diseases, in the present study we interviewed 367 patients and tested their blood samples for HCV antibodies (anti-HCV by an enzyme-linked immunosorbent assay. Anti-HCV-reactive samples were retested for confirmation by a line immunoassay and also for HCV RNA detection by the polymerase chain reaction. HCV RNA-positive samples were genotyped by INNO-LIPA. An overall HCV infection prevalence of 1.9% (7/367 was found. Of the 7 HCV-infected patients, 4 had systemic lupus erythematosus and 3 rheumatoid arthritis, resulting in positivity rates of 2.3 and 3.4%, respectively. HCV RNA genotyping revealed the presence of subtypes 1a (57.1%, 1b (28.6% and 3a (14.3%. The clinical course was favorable for all HCV-infected patients, except one, who died due to renal insufficiency related to lupus nephritis. These results demonstrate a low HCV infection prevalence among the population studied. In the few positive cases, we observed no adverse influence of this infection on the clinical evolution of the rheumatic disease.

  2. Comparative genotyping of Campylobacter jejuni strains from patients with Guillain-Barre syndrome in Bangladesh.

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    Zhahirul Islam

    Full Text Available BACKGROUND: Campylobacter jejuni is a common cause of acute gastroenteritis and is associated with post-infectious neuropathies such as the Guillain-Barré syndrome (GBS and the Miller Fisher syndrome (MFS. We here present comparative genotyping of 49 C. jejuni strains from Bangladesh that were recovered from patients with enteritis or GBS. All strains were serotyped and analyzed by lipo-oligosaccharide (LOS genotyping, amplified fragment length polymorphism (AFLP analysis, multilocus sequence typing (MLST, and pulsed-field gel electrophoresis (PFGE. METHODOLOGY/PRINCIPAL FINDINGS: C. jejuni HS:23 was a predominant serotype among GBS patients (50%, and no specific serotype was significantly associated with GBS compared to enteritis. PCR screening showed that 38/49 (78% of strains could be assigned to LOS classes A, B, C, or E. The class A locus (4/7 vs 3/39; p<0.01 was significantly associated in the GBS-related strains as compared to enteritis strains. All GBS/oculomotor related strains contained the class B locus; which was also detected in 46% of control strains. Overlapping clonal groups were defined by MLST, AFLP and PFGE for strains from patients with gastroenteritis and GBS. MLST defined 22 sequence types (STs and 7 clonal complexes including 7 STs not previously identified (ST-3742, ST-3741, ST-3743, ST-3748, ST-3968, ST-3969 and ST-3970. C. jejuni HS:23 strains from patients with GBS or enteritis were clonal and all strains belonged to ST-403 complex. Concordance between LOS class B and ST-403 complex was revealed. AFLP defined 25 different types at 90% similarity. The predominant AFLP type AF-20 coincided with the C. jejuni HS:23 and ST-403 complex. CONCLUSION/SIGNIFICANCE: LOS genotyping, MLST, AFLP and PFGE helped to identify the HS:23 strains from GBS or enteritis patients as clonal. Overall, genotypes exclusive for enteritis or for GBS-related strains were not obtained although LOS class A was significantly associated with GBS

  3. Proifle, spectrum and signiifcance of hepatitis B virus genotypes in chronic HBV-infected patients in Yunnan, China

    Institute of Scientific and Technical Information of China (English)

    Jing You; Bao-Zhang Tang; Hutcha Sriplung; Virasakdi Chongsuvivatwong; Alan Geater; Lin Zhuang; Jun-Hua Huang; Hong-Ying Chen; Lan Yu

    2008-01-01

    BACKGROUND:There are signiifcant variations in the geographical distribution of hepatitis B virus (HBV) genotypes throughout the world, and some genotypes are associated with different clinical outcomes. Eight genotypes of human HBV (designated A-H) have been reported. The present study was designed to examine the distribution of HBV genotypes among patients at various stages of chronic type B liver disease in Yunnan Province, China, and to explore its signiifcance and the relationship of HBV genotype with gender and age, clinical spectrum of chronic HBV infection, and viral replicative activity. METHODS:Serum samples from 126 patients with chronic HBV infection from Yunnan Province, including 26 chronic asymptomatic HBV carriers (ASC), 61 patients with chronic hepatitis B (CHB) (21 mild, 30 moderate and 10 severe), 20 patients with chronic fulminant hepatic failure (CFHF), 12 patients with HBV-related liver cirrhosis (LC) and 7 patients with HBV-related hepatocellular carcinoma (HCC) were analyzed using reverse dot blot (RDB) methodology, which is based on the reverse hybridization principle for HBV genotyping. The relations of HBV genotype with gender and age, clinical patterns, and serological data of the patients were analyzed. RESULTS: In this series, genotypes A, B, C, and D were found. 38.1%patients (48/126) belonged to B, 54.8%(69/126) to C, 0.8%(1/126) to D, 1.6%(2/126) to a mixture of B and C, and 1.6%(2/126) to a mixture of A and C. 3.2%patients (4/126) had unknown genotypes. No other genotypes (E, F, G, and H) were found. Genotypes B and C were predominant. There was a statistically signiifcant difference in the distributions of genotypes C and B (χ2=7.04, P=0.008), and C was the dominant genotype in all patient categories. The rate of genotype B in the mild CHB group was signiifcantly higher than that in the moderate and severe groups (χ2=12.16, P=0.0001; χ2=11.98, P=0.001, respectively), the ASC group (χ2=5.46, P=0.02), the CFHF group (χ2

  4. Limited protective effect of the CCR5Δ32/CCR5Δ32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus

    DEFF Research Database (Denmark)

    Iversen, Astrid K. N.; Christiansen, Claus Bohn; Attermann, Jørn

    2003-01-01

    The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)–infected patients with hemophilia. One patient (0.6%) had the CCR5Δ32/CCR5Δ32 genotype (which occurs in ∼2% of the Scandinavian population...

  5. Prevalence of Warfarin Genotype Polymorphisms in Patients with Mechanical Circulatory Support.

    Science.gov (United States)

    Awad, Morcos; Czer, Lawrence S C; Soliman, Camelia; Mirocha, James; Ruzza, Andrea; Pinzas, Joshua; Rihbany, Kelsey; Chang, David; Moriguchi, Jaime; Ramzy, Danny; Esmailian, Fardad; Kobashigawa, Jon; Arabia, Francisco

    2015-01-01

    Polymorphisms for VKORC1 and CYP2C9 are associated with increased warfarin sensitivity. The prevalence of these polymorphisms in patients with mechanical circulatory support (MCS) is unknown. Polymorphisms for VKORC1 and CYP2C9 were determined in 65 patients undergoing MCS surgery. Postoperative warfarin dose, international normalized ratio (INR), and bleeding events were measured until discharge, 6 months, or composite end point (in-hospital MCS recovery, heart transplant, or death). A total of 67.7% (44/65) had at least one polymorphism: VKORC1 (44.6%), CYP2C9*2 (7.7%), CYP2C9*3 (4.6%), CYP2C9*2 and VKORC1 (3.1%), or CYP2C9*3 and VKORC1 (7.7%). At discharge or before composite end point, patients with any polymorphism received a lower mean warfarin dosage than patients having no polymorphism (3.21 ± 1.47 vs. 5.57 ± 3.72 mg, p = 0.015) and achieved a similar mean INR (2.20 ± 0.67 vs. 2.19 ± 0.69, p = 0.96). There was no significant difference in bleeding rates within 6 months or before composite end point (6.13 vs. 8.02 events/patient-year, p = 0.13). One or more polymorphisms for VKORC1 or CYP2C9 (associated with warfarin sensitivity) were found in 67.7% of MCS patients. By using a warfarin genotype-guided approach, MCS patients with polymorphisms received a lower warfarin dosage to achieve a similar INR, with similar bleeding rates, in comparison with no polymorphisms. A warfarin genotype-guided approach avoided excessive anticoagulation and its attendant bleeding risks.

  6. Influence of Acanthamoeba genotype on clinical course and outcomes for patients with Acanthamoeba keratitis in Spain.

    Science.gov (United States)

    Arnalich-Montiel, Francisco; Lumbreras-Fernández, Blanca; Martín-Navarro, Carmen M; Valladares, Basilio; Lopez-Velez, Rogelio; Morcillo-Laiz, Rafael; Lorenzo-Morales, Jacob

    2014-04-01

    Genotype T4 is by far the most frequent genotype of Acanthamoeba keratitis (AK) and therefore has been considered the most virulent. This study included 14 cases of AK of genotype T4 and three cases of non-T4 genotype. We found that cases of non-T4 genotype had a worse response to medical therapy, greater need for surgical intervention, greater risk of extracorneal involvement, and remarkably poorer final visual outcome than those of T4 genotype, suggesting an association between Acanthamoeba virulence and genotype that requires additional case investigation.

  7. Phenotype and Genotype of Enterococcus faecalis Isolated form Root Canal and Saliva of Primary Endodontic Patients

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    Zaki Mubarak

    2016-04-01

    Full Text Available This study was carried out to investigate the phenotype and genotype of E. faecalis isolated from the root canal and saliva of primary endodontic patients with periapical lesions. Eighteen adult male and female individuals suffering from primary endodontic infection, either had or had not periapical lesions, were involved in this study. Root canal scraping and saliva were collected from each subject and used for bacterial quantitation using a real-time polymerase chain reaction (RT-PCR. Enterococci were isolated using ChromAgar medium and then identified using both biochemical (Gram staining and catalase tests and molecular biology (conventional PCR methods. Gelatinase activity, polysaccharide capsul profile and mRNA ace expression level were determined using microbiological, biochemical and molecular biology approach, respectively.  Genotype of E. faecalis was determined based on nucleotide sequence of ace and gelE genes analyzed using web-based 3730xl DNA Analyze software. The results showed that high proportion of E. faecalis found in both root canal and saliva of is related to the incidence of periapical lessions in the primary endodontic patients. This is contrast to the insignificant relationship found between Cps polymorphism, gelatinase activity, and mRNA ace expression with periapical lesions in the patients, respectively.DOI: 10.14693/jdi.v23i1.960

  8. Mutational analysis of paediatric patients with tuberous sclerosis complex in Korea: genotype and epilepsy.

    Science.gov (United States)

    Lee, Jin Sook; Lim, Byung Chan; Chae, Jong-Hee; Hwang, Yong Seung; Seong, Moon-Woo; Park, Sung Sup; Kim, Ki Joong

    2014-12-01

    To date, only a few studies have reported that, in tuberous sclerosis, TSC2 mutations are more frequently associated with infantile spasms and cognitive impairment compared to TSC1 mutations. We analyzed the mutational spectrum of patients with tuberous sclerosis in Korea and attempted to explore the associations between genotype and seizure type/outcome. We performed mutational analyses on 70 unrelated patients with clinically confirmed tuberous sclerosis by using direct DNA sequencing and/or multiplex ligation-dependent probe amplification. The patients' medical records, including epilepsy type and outcome, were reviewed retrospectively. We identified pathogenic mutations in 55 patients (79%), 25 of which were novel. There were 12 TSC1 mutations and 43 TSC2 mutations. TSC1 mutations included 8 frameshift and 4 nonsense mutations. TSC2 mutations included 12 frameshift, 10 nonsense, 6 splicing, and 6 missense mutations, as well as 4 in-frame deletions and 5 large deletions. Fifty-eight patients had epilepsy (83%), including 19 patients with a history of infantile spasms. Compared to patients with TSC1 mutations, individuals with TSC2 mutations had a significantly higher frequency of epilepsy (p<0.05) and tended to have a higher frequency of infantile spasms (37% vs 17%; p<0.3). Most of the patients with TSC2 mutations who developed infantile spasms exhibited subsequent epilepsy (13/14; 93%). However, the presence/absence of infantile spasms did not influence seizure remission or cognitive outcome.

  9. Implementing CHC to Counter Shoulder Surfing Attack in PassPoint – Style Graphical Passwords

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    M. Joshuva

    2011-05-01

    Full Text Available Graphical passwords are an alternative to existing alphanumeric passwords. In Graphical passwords users click on images than type a long, complex password. Passpoints scheme is one of the Graphical user authentication techniques. In this method the password is represented by multiple clicks on a single image. One of the advantages with Passpoints scheme is that, a user can click on any place in the image as a click point. Graphical authentication suffers a major drawback of Shoulder-surfing. Shoulder-surfing refers to someone observing the user’s action as the user enters a password. Due to this, the user’s action can be monitored by the attacker or it can be captured using recording devices such as camera. Sobrado and Birget suggested Convex Hull Click (CHC scheme to counter shoulder-surfing using PassIcons which is different from PassPoint scheme. In this paper, we described how CHC is implemented in Passpoint-sheme to counter Shoulder Surfing Attack.

  10. Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction

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    Seljeflot Ingebjørg

    2008-06-01

    Full Text Available Abstract Background Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfarin treatment reduced thrombotic events, but was associated with more frequent bleeding than use of acetylsalisylic acid (ASA alone. Aims The primary aim of the present study was to investigate the relation between genotypes of CYP2C9 and VKORC1 and warfarin maintenance dose in myocardial infarction. The secondary aim was to relate the genotypes to international normalized ratio (INR. Methods Genotyping was performed in 212 myocardial infarction patients from the WARIS-II study by robotic isolation of DNA from EDTA whole blood (MagNa Pure LC before PCR amplification (LightCycler and melting point analysis. Results The 420 C>T substitution of CYP2C9*2, the 1075 A>C substitution of CYP2C9*3 and the 1173 C>T substitution of VKORC1 had minor allele frequencies of, 11.3%, 5.7% and 36.6% respectively. Warfarin weekly dose varied between 17 mg and 74 mg among the patients. INR did not vary between genotypes. Warfarin dosage requirement was significantly associated with CYP2C9 and VKORC1 genotypes, treatment group and age. The VKORC1 genotype contributed 24.5% to the interindividual variation in warfarin dosage, whereas the combined CYP2C9 genotypes were only responsible for 7.2% of the dose variation. Conclusion CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.

  11. Relationship of sleep abnormalities to patient genotypes in Prader-Willi syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Vgontzas, A.N.; Kales, A.; Bixler, E.O. [Pennsylvania State Univ., Hershey, PA (United States)] [and others

    1996-09-20

    To assess whether sleep abnormalities are related to the genetic abnormalities in Prader-Willi Syndrome (PWS), we performed polysomnographic studies (nighttime and daytime) and determined the chromosome 15 genotypes in eight patients with PWS. Four patients demonstrated sleep onset REM periods (SOREM), and five met the objective polysomnographic criteria for severe or moderate excessive daytime sleepiness (EDS). Three of the four patients with SOREM displayed a paternally derived deletion of chromosome 15q11-q13, whereas the fourth exhibited maternal uniparental heterodisomy in this chromosomal region (UPD). Two of the four patients that did not display SOREM carried paternally derived deletions; the remaining two demonstrated UPD. Four of the five patients with EDS displayed paternal deletions, and the fifth exhibited UPD. One of three patients without evidence of EDS demonstrated paternal deletion; the remaining two showed UPD. Although neither EDS nor SOREM was not consistently associated with a specific genetic abnormality, these phenotypes may be more common in patients with paternal deletions than in those with UPD. Sleep abnormalities in PWS cannot be explained by a single genetic model. 32 refs., 1 tab.

  12. Efficacy of raltegravir switching strategies in HIV-infected patients with suppressed viraemia according to the genotypic sensitivity score.

    Science.gov (United States)

    Caby, F; Schneider, L; Blanc, C; Soulié, C; Tindel, M; Peytavin, G; Agher, R; Valantin, M A; Tubiana, R; Wirden, M; Calvez, V; Marcelin, A G; Katlama, C

    2014-04-01

    The lack of antiretroviral (ARV) backbone activity associated with raltegravir has been proposed as the main explanation for virological relapse observed in patients with undetectable viraemia who are switched from a ritonavir-boosted protease inhibitor (PI) to raltegravir. However ARV activity remains difficult to assess in this context. The aim of our study was to precisely assess the ARV backbone activity in patients with undetectable viraemia who underwent raltegravir switching strategies and to evaluate the efficacy of such switching strategies based on the genotypic sensitivity score (GSS). Patients with a plasma human immunodeficiency virus type 1 (HIV-1) RNA level of HIV-1 RNA of the last plasma measurement with a HIV-1 RNA level of >50 copies/mL before the switch and on the results of all previous genotyping tests. The primary endpoint was the proportion of patients with a plasma HIV-1 RNA level of HIV-1 RNA level of HIV-RNA genotyping test results.

  13. Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype Distribution in Familial Mediterranean Fever (FMF) Patients.

    Science.gov (United States)

    Erken, Ertugrul; Goruroglu Ozturk, Ozlem; Kudas, Ozlem; Arslan Tas, Didem; Demirtas, Ahmet; Kibar, Filiz; Dinkci, Suzan; Erken, Eren

    2015-11-17

    BACKGROUND Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease predominantly affecting Mediterranean populations. The gene associated with FMF is the MEFV gene, which encodes for a protein called pyrin. Mutations of pyrin lead to uncontrolled attacks of inflammation, and subclinical inflammation continues during attack-free intervals. Killer cell immunoglobulin-like receptor (KIR) genes encode HLA class I receptors expressed by NK cells. The aim this study was to look for immunogenetic determinants in the pathogenesis of FMF and find out if KIR are related to susceptibility to disease or complications like renal amyloidosis. MATERIAL AND METHODS One hundred and five patients with FMF and 100 healthy individuals were involved in the study. Isolated DNA from peripheral blood was amplified by sequence specific PCR probes and analyzed by Luminex for KIR genotypes. Fisher Exact test was used to evaluate the variation of KIR gene distribution. RESULTS All patients and healthy controls expressed the framework genes. An activator KIR gene, KIR2DS2, was significantly more frequent in FMF patients (p=0.036). Renal amyloidosis and presence of arthritis were not associated with KIR genes and genotype. KIR3DL1 gene was more common in patients with high serum CRP (p=0.016). CONCLUSIONS According to our findings, we suggest that presence of KIR2DS2, which is an activator gene for NK cell functions, might be related to the autoinflammation in FMF. The potential effect of KIR genes on amyloidosis and other clinical features requires studies with larger sample sizes.

  14. Angiotensin-Converting Enzyme Genotype and Peripheral Arterial Disease in Diabetic Patients

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    Chin-Hsiao Tseng

    2012-01-01

    Full Text Available We investigated the effect of traditional risk factors (hypertension, dyslipidemia and smoking on the association between angiotensin-converting enzyme (ACE gene insertion/deletion (I/D polymorphism and peripheral arterial disease (PAD in 945 (454 men and 491 women Taiwanese type 2 diabetic patients with a mean age of 63.5 (SD: 11.4 years. Among them, 81 (31 men and 50 women had PAD (ankle-brachial index <0.9. The adjusted odds ratios (95% confidence intervals were 2.48 (1.18–5.21, 1.69 (1.00–2.85 and 1.64 (1.12–2.39, respectively, for recessive (DD versus II + ID, dominant (DD + ID versus II and additive (II = 0, ID = 1 and DD = 2 models. While analyzing the interaction between DD and the individual risk factor of hypertension, smoking and dyslipidemia, patients with the risk factor and with DD had the highest risk compared to referent patients without the risk factor and with II/ID. The respective adjusted odds ratios were 5.41 (2.05–14.31, 7.38 (1.87–29.06 and 4.64 (1.70–12.64. We did not find a significant interaction between DD and any of the risk factors under multiplicative or additive scale. In conclusion, traditional risk factors (hypertension, smoking and dyslipidemia play an important role in the association between ACE genotypes and PAD. Patients with DD genotype and traditional risk factors are at the highest risk.

  15. Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4

    Science.gov (United States)

    Rizk, Hanan H.; Hamdy, Nadia M.; Al-Ansari, Nadia L.; El-Mesallamy, Hala O.

    2016-01-01

    Background Egypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA-4), could be candidate markers predicting treatment response. Methods This cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN α-2a and RBV in 2 hepatology centers. Genotyping of the polymorphisms in the IL28B gene region (rs12979860), PD1.3 (rs11568821) and CTLA-4 (rs231775) was performed on DNA collected from each patient using TaqMan® genotyping assay. Groups were classified according to response into sustained virological responders (SVR), or non-responders (NR). A multivariate logistic regression analysis was used to identify potential markers, host pretreatment clinical and viral predictive factors including viral load, insulin resistance, and alpha fetoprotein (AFP) related to treatment response. Results Our results showed that in a multivariate analyses IL28B C/C genotype was the most significant predictor for SVR (OR = 10.86; p<0.0001) followed by AFP (OR = 0.915; p = 0.001) then CTLA-4/G genotypes (OR = 1.948; p = 0.022). However, PD-1.3/A genotypes and platelets count were significantly related to response in univariate analysis only (OR = 1.973; p = 0.023; OR = 1.007; p = 0.009 respectively). Conclusion IL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients. PMID:27100663

  16. Hepatitis B virus genotypes and mutations in the basal core promoter and pre-core/core in chronically infected patients in southern Brazil: a cross-sectional study of HBV genotypes and mutations in chronic carriers

    Directory of Open Access Journals (Sweden)

    Flávia Miryan Martins Almeida de Mello

    2014-12-01

    Full Text Available Introduction In Brazil, little data exist regarding the distribution of genotypes in relation to basal core promoter (BCP and precore/core mutations among chronic hepatitis B virus (HBV carriers from different regions of the country. The aim of this study was to identify HBV genotypes and the frequency of mutations at the BCP and precore/core region among the prevalent genotypes in chronic carriers from southern Brazil. Methods Nested-polymerase chain reaction (nested-PCR products amplified from the S-polymerase gene, BCP and precore/core region from 54 samples were sequenced and analyzed. Results Phylogenetic analysis of the S-polymerase gene sequences showed that 66.7% (36/54 of the patients were infected with genotype D (D1, D2, D3, 25.9% (14/54 with genotype A (A1, A2, 5.6% (3/54 with subgenotype C2, and 2% (1/54 with genotype E. A comparison of virological characteristics showed significant differences between genotypes A, C and D. The comparison between HBeAg status and the G1896A stop codon mutation in patients with genotype D revealed a relationship between HBV G1896A precore mutants and genotype D and hepatitis B e antigen (HBeAg seroconversion. Genotype D had a higher prevalence of the G1896A mutation and the presence of a thymine at position 1858. Genotype A was associated with a higher prevalence of the G1862T mutation and the presence of a cytosine at position 1858. Conclusions HBV genotype D (D3 is predominant in HBV chronic carriers from southern Brazil. The presence of mutations in the BCP and precore/core region was correlated with the HBV genotype and HBeAg negative status.

  17. Effect of laparoscopic splenectomy in patients with Hepatitis C and cirrhosis carrying IL28B minor genotype

    Directory of Open Access Journals (Sweden)

    Motomura Takashi

    2012-11-01

    Full Text Available Abstract Background IL28B and ITPA genetic variants are associated with the outcome of pegylated-interferon and ribavirin (PEG-IFN/RBV therapy. However, the significance of these genetic variants in cirrhotic patients following splenectomy has not been determined. Methods Thirty-seven patients with HCV-induced cirrhosis who underwent laparoscopic splenectomy (Spx group and 90 who did not (non-Spx group were genotyped for IL28B and ITPA. The outcome or adverse effects were compared in each group. Interferon-stimulated gene 15 (ISG15 and protein kinase R expression in the spleen was measured using total RNA extracted from exenterate spleen. Results Sustained virological response (SVR rate was higher in patients carrying IL28B major genotype following splenectomy (50% vs 27.3% and in patients carrying minor genotype in the Spx group compared to non-Spx group (27.3% vs 3.6%, P 3/μl vs 168.7 × 103/μl, P Conclusions IL28B genetic variants correlated with response to PEG-IFN/RBV following splenectomy. Splenectomy improved SVR rate among patients carrying IL28B minor genotype and protected against anemia and thrombocytopenia during the course of PEG-IFN/RBV therapy regardless of ITPA genotype.

  18. Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever: differences in genotype and clinical features between Japanese and Mediterranean populations.

    Science.gov (United States)

    Kishida, Dai; Nakamura, Akinori; Yazaki, Masahide; Tsuchiya-Suzuki, Ayako; Matsuda, Masayuki; Ikeda, Shu-ichi

    2014-09-27

    Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis that mainly affects Mediterranean populations. Many patients with FMF have been reported in Japan due to increasing recognition of this condition and the availability of genetic analysis for the gene responsible, MEFV. The present study was performed to elucidate the clinical characteristics of Japanese FMF patients and to examine the precise genotype-phenotype correlation in a large cohort of Japanese FMF patients. We analyzed the MEFV genotypes and clinical manifestations in 116 patients clinically diagnosed as having FMF and with at least one mutation. The most frequent mutation in Japanese patients was E148Q (40.2%), followed by M694I (21.0%), L110P (18.8%), P369S (5.4%), and R408Q (5.4%). In contrast, common mutations seen in Mediterranean patients, such as M694V, V726A, and M680I, were not detected in this population. The clinical features with M694I were associated with more severe clinical course compared to those seen with E148Q. P369S/R408Q showed variable phenotypes with regard to both clinical manifestations and severity. Patients with M694I showed a very favorable response to colchicine therapy, while those with P369S and R408Q did not. Clinical features and efficacy of treatment in Japanese FMF patients vary widely according to the specific MEFV gene mutation, and therefore genetic analysis should be performed for diagnosis in cases of Japanese FMF.

  19. Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients.

    Science.gov (United States)

    Igumnova, Viktorija; Capligina, Valentina; Krams, Alvils; Cirule, Andra; Elferts, Didzis; Pole, Ilva; Jansone, Inta; Bandere, Dace; Ranka, Renate

    2016-07-01

    Pharmacogenomic testing of tuberculosis drug-metabolizing enzyme genes was proposed as a strategy to identify patients at risk for suboptimal responses to medications. However, variations of the genotype frequencies among ethnic groups exist and new alleles are been identified. The aim of this study was to identify polymorphisms of genes encoding metabolic enzymes NAT2 and GSTM1 in tuberculosis patients in Latvia and to estimate the frequency of NAT2 slow acetylator and GSTM1 null genotypes. In total, 85 DNA samples were genotyped, all individuals were Caucasian. An ethnic heterogeneity reflecting the multiethnic population of the country was observed. 49 patients were Latvians, 30 were Russians and 6 of other ethnicity. In total, 7 NAT2 alleles were identified: *4, *5, *6, *7, *11, *12, * and *13. The most frequent was the slow acetylation allele NAT2*6 (frequency 0.388) followed by the slow acetylation allele NAT2*5 and the rapid acetylation allele NAT2*4 (frequencies 0.306 and 0.194, respectively). The predominance of slow (51.8%) and intermediate (43.5%) acetylators compared with rapid acetylators (4.7%) was observed. The GSTM1 null genotype was detected in 48.2% of tuberculosis patients. When subgroup analysis was performed according to ethnicity, the results showed that neither NAT2 allele frequencies nor GSTM1 null genotype frequency did not differ significantly in TB patients of Latvian or Russian ethnicity. Overall, genotyping results were similar with previous reports of a NAT2 gene variation and GSTM1 null genotype frequency in Caucasians. Our findings have a contribution for the pharmacogenetics-based tuberculosis therapy in Latvia in future.

  20. Correlation of ATP7B genotype with phenotype in Chinese patients with Wilson disease

    Institute of Scientific and Technical Information of China (English)

    Xiao-Qing Liu; Ya-Fen Zhang; Tze-Tze Liu; Kwang-Jen Hsiao; Jian-Ming Zhang; Xue-Fan Gu; Ke-Rong Bao; Li-Hua Yu; Mei-Xian Wang

    2004-01-01

    AIM: To determine the mutational characterization of Ptype ATP7B gene and to explore the correlation of ATP7B genotype to phenotype in Chinese patients with Wilson disease (WD).METHODS: Seventy-five patients with WD from 72 no-kinship families, 44 males and 31 females, were enrolled in this study.The age of onset ranged from 4 to 39 years, ≤18 years in 72 patients. Some exons of ATP7B gene mutations were analyzed in patients with WD by using biochemical methods,polymerase chain reaction-single strand configuration polymorphism (PCR-SSCP) and DNA sequence analysis. A total of 778 coding regions were identified with restriction enzyme Msp I. The activity of Cu-ATPase was assessed by measuring inorganic phosphorus.RESULTS: Sixty-six of 75 patients (88%) had with hepatic manifestations, 39 of them had only hepatic manifestations,27 patients had hepatic and neurological manifestations or other symptoms at the same time (16 patients had associated neurological manifestation, 3 patients had osteopathy, 8patients had other symptoms). Eight of the 75 patients (10.7%) had only neurological symptoms, one patient (5 years old) had no symptom. Twelve changing patterns were detected in ATP7B gene by DNA sequencing, including seven mutations (R778L, C656X, G943D, V1140A, V1106I V1216M and 1384del17), six polymorphisms (IVS4-5t/c, A2495G, C2310G,IVS18+6c/t and IVS20+5a/g). R778L occurred in 49/66patients (74%) with hepatic manifestations, homozygosis of R778L in 16 patients, heterozygosity of R778L in 33 patients. V1106I mutation of ATP7B gene occurred in 2 patients with delaying onset of clinical symptoms. Cu-ATPase activity of three patients with known mutations (R778L/ V1106I/A2495G, R778L/V1216M and R778L/R778L) were determined; and the activity of Cu-ATPase was decreased by 44.55%, 88.23% and 69.49% respectively.CONCLUSION: 1384del17bp is a novel mutation found in WD patients. R778L is the most common mutation of ATP7B gene. There is a correlation between R778L and hepatic

  1. Emerging genotype-phenotype relationships in patients with large NF1 deletions.

    Science.gov (United States)

    Kehrer-Sawatzki, Hildegard; Mautner, Victor-Felix; Cooper, David N

    2017-04-01

    The most frequent recurring mutations in neurofibromatosis type 1 (NF1) are large deletions encompassing the NF1 gene and its flanking regions (NF1 microdeletions). The majority of these deletions encompass 1.4-Mb and are associated with the loss of 14 protein-coding genes and four microRNA genes. Patients with germline type-1 NF1 microdeletions frequently exhibit dysmorphic facial features, overgrowth/tall-for-age stature, significant delay in cognitive development, large hands and feet, hyperflexibility of joints and muscular hypotonia. Such patients also display significantly more cardiovascular anomalies as compared with patients without large deletions and often exhibit increased numbers of subcutaneous, plexiform and spinal neurofibromas as compared with the general NF1 population. Further, an extremely high burden of internal neurofibromas, characterised by >3000 ml tumour volume, is encountered significantly, more frequently, in non-mosaic NF1 microdeletion patients than in NF1 patients lacking such deletions. NF1 microdeletion patients also have an increased risk of malignant peripheral nerve sheath tumours (MPNSTs); their lifetime MPNST risk is 16-26%, rather higher than that of NF1 patients with intragenic NF1 mutations (8-13%). NF1 microdeletion patients, therefore, represent a high-risk group for the development of MPNSTs, tumours which are very aggressive and difficult to treat. Co-deletion of the SUZ12 gene in addition to NF1 further increases the MPNST risk in NF1 microdeletion patients. Here, we summarise current knowledge about genotype-phenotype relationships in NF1 microdeletion patients and discuss the potential role of the genes located within the NF1 microdeletion interval whose haploinsufficiency may contribute to the more severe clinical phenotype.

  2. Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: correlation with phenotype and genotype.

    Science.gov (United States)

    Orvisky, Eduard; Park, Joseph K; LaMarca, Mary E; Ginns, Edward I; Martin, Brian M; Tayebi, Nahid; Sidransky, Ellen

    2002-08-01

    Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, presents with a wide spectrum of clinical manifestations including neuronopathic and non-neuronopathic forms. While the lipid glucosylceramide is stored in both patients with Gaucher disease and in a null allele mouse model of Gaucher disease, elevated levels of a second potentially toxic substrate, glucosylsphingosine, are also found. Using high performance liquid chromatography, glucosylsphingosine levels were measured in tissues from patients with type 1, 2, and 3 Gaucher disease. Glucosylsphingosine was measured in 16 spleen samples (8 type 1; 4 type 2; and 4, type 3) and levels ranged from 54 to 728 ng/mg protein in the patients with type 1 disease, 133 to 1200 ng/mg protein in the patients with type 2, and 109 to 1298 ng/mg protein in the type 3 samples. The levels of splenic glucosylsphingosine bore no relation to the type of Gaucher disease, the age of the patient, the genotype, nor the clinical course. In the same patients, hepatic glucosylsphingosine levels were lower than in spleen. Glucosylsphingosine was also measured in brains from 13 patients (1 type 1; 8 type 2; and 4 type 3). While the glucosylsphingosine level in the brain from the type 1 patient, 1.0 ng/mg protein, was in the normal range, the levels in the type 3 samples ranged from 14 to 32 ng/mg protein, and in the type 2 samples from 24 to 437 ng/mg protein, with the highest values detected in two fetuses with hydrops fetalis. The elevated levels found in brains from patients with neuronopathic Gaucher disease support the hypothesis that glucosylsphingosine may contribute to the nervous system involvement in these patients.

  3. Comparison of genotypic resistance profiles and virological response between patients starting nevirapine and efavirenz in EuroSIDA

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Ruiz, Lidia; Cozzi-Lepri, Alessandro

    2008-01-01

    OBJECTIVE: To compare virological outcome and genotypic resistance profiles in HIV-1-infected patients starting non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens. METHODS: NNRTI-naive patients were included who started treatment with nevirapine (NVP) or efavirenz (EFV) wi...

  4. Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype.

    Science.gov (United States)

    Reiner, I; Van IJzendoorn, M H; Bakermans-Kranenburg, M J; Bleich, S; Beutel, M; Frieling, H

    2015-06-01

    The emerging field of epigenetics provides a biological basis for gene-environment interactions relevant to depression. We focus on DNA methylation of exon 1 and 2 of the oxytocin receptor gene (OXTR) promoter. The research aims of the current study were to compare OXTR DNA methylation of depressed patients with healthy control subjects and to investigate possible influences of the OXTR rs53576 genotype. The sample of the present study consisted of 43 clinically depressed women recruited from a psychosomatic inpatient unit and 42 healthy, female control subjects - mean age 30 years (SD = 9). DNA methylation profiles of the OXTR gene were assessed from leukocyte DNA by means of bisulfite sequencing. Depressed female patients had decreased OXTR exon 1 DNA methylation compared to non-depressed women. The association between depression and methylation level was moderated by OXTR rs53576 genotype. Exon 2 methylation was associated with OXTR rs53576 genotype but not with depression. Our findings suggest exon-specific methylation mechanisms. Exon 1 methylation appears to be associated with depressive phenotypes whereas exon 2 methylation is influenced by genotype. Previously reported divergent associations between OXTR genotype and depression might be explained by varying exon 1 methylation. In order to further understand the etiology of depression, research on the interplay between genotype, environmental influences and exon-specific methylation patterns is needed.

  5. Helicobacter Genotyping and Detection in Peroperative Lavage Fluid in Patients with Perforated Peptic Ulcer

    NARCIS (Netherlands)

    N.A.P. Komen (Niels); M.J.O.E. Bertleff (Marietta); J.F. Lange (Johan); P.W. de Graaf

    2008-01-01

    textabstractIntroduction and Objectives Certain Helicobacter pylori genotypes are associated with peptic ulcer disease; however, little is known about associations between the H. pylori genotype and perforated peptic ulcer (PPU). The primary aim of this study was to evaluate which genotypes are pre

  6. Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations.

    LENUS (Irish Health Repository)

    Geranmayeh, Fatemeh

    2010-04-01

    Merosin deficient congenital muscular dystrophy 1A (MDC1A) results from mutations in the LAMA2 gene. We report 51 patients with MDC1A and examine the relationship between degree of merosin expression, genotype and clinical features. Thirty-three patients had absence of merosin and 13 showed some residual merosin. Compared to the residual merosin group, patients with absent merosin had an earlier presentation (<7days) (P=0.0073), were more likely to lack independent ambulation (P=0.0215), or require enteral feeding (P=0.0099) and ventilatory support (P=0.0354). We identified 33 novel LAMA2 mutations; these were distributed throughout the gene in patients with absent merosin, with minor clusters in exon 27, 14, 25 and 26 (55% of mutations). Patients with residual merosin often carried at least one splice site mutation and less frequently frameshift mutations. This large study identified novel LAMA2 mutations and highlights the role of immunohistochemical studies for merosin status in predicting clinical severity of MDC1A.

  7. High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer

    OpenAIRE

    Yolanda López-Vidal; Sergio Ponce-de-León; Gonzalo Castillo-Rojas; Rafael Barreto-Zúñiga; Aldo Torre-Delgadillo

    2008-01-01

    BACKGROUND: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biops...

  8. Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    José Eymard Medeiros-Filho; Isabel Maria Vicente Guedes de Carvalho Mello; Jo(a)o Renato Rebello Pinho; Avidan U Neumann; Fernanda de Mello Malta; Luiz Caetano da Silva; Flair José Carrilho

    2006-01-01

    AIM: To evaluate the impact of hepatitis C virus (HCV)infection with genotype 1 or 3 and the presence or absence of liver cirrhosis (LC) in the early viral kinetics response to treatment.METHODS: Naive patients (n = 46) treated with interferon-α (IFN-α) and ribavirin and followed up with frequent early HCV-RNA determinations were analysed.Patients were infected with genotype 1 (n = 28, 7 with LC) or 3 (n = 18, 5 with LC).RESULTS: The first phase decline was larger in genotype 3 patients than in genotype 1 patients (1.72 vs 0.95log IU/mL, P < 0.001). The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients (0.87 vs 0.15 log/wk, P < 0.001). Differences were found in both cirrhotic and non-cirrhotic patients.Genotype 1 cirrhotic patients had a slower 2nd phase slope than non-cirrhotic patients (0.06 vs 0.18 log/wk, P< 0,02). None of genotype 1 cirrhotic patients had a 1stphase decline larger than 1 log (non-cirrhotic patients:55%, P < 0.02). A similar trend toward a slower 2ndphase slope was observed in genotype 3 cirrhotic patients but the 1st phase slope decline was not different.Sustained viral response was higher in genotype 3 patients than in genotype 1 patients ,(72% vs14%, P <0.001) and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients (19% vs 0%). A second phase decline slower than 0.3 log per week was predictive of non-response in all groups.CONCLUSION: Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1st phase slope decline in genotype 1 patients.

  9. Associations of GSTM1*0 and GSTA1*A genotypes with the risk of cardiovascular death among hemodialyses patients.

    Science.gov (United States)

    Suvakov, Sonja; Damjanovic, Tatjana; Pekmezovic, Tatjana; Jakovljevic, Jovana; Savic-Radojevic, Ana; Pljesa-Ercegovac, Marija; Radovanovic, Slavica; Simic, Dragan V; Pljesa, Steva; Zarkovic, Milos; Mimic-Oka, Jasmina; Dimkovic, Nada; Simic, Tatjana

    2014-01-14

    The presence of glutathione transferase (GST) M1 null genotype (GSTM1-null) in end-stage renal disease (ESRD) patients is associated with lower overall survival rate in comparison to those with GSTM1-active variants. We examined association between GSTM1 and GSTT1 deletion polymorphisms as well as SNPs in GSTA1/rs3957357 and GSTP1/rs1695 genes with overall and cause-specific cardiovascular mortality in ESRD patients. Total of 199 patients undergoing hemodialysis were included in the study. Median value of time elapsed from dialysis initiation until the death, or the end of follow-up was 8 ± 5 years. The effect of GSTM1, GSTT1, GSTP1 and GSTA1 gene polymorphisms on predicting overall and specific cardiovascular outcomes (myocardial infarction, MI or stroke) was analyzed using Cox regression model, and differences in survival were determined by Kaplan-Meier. GSTM1-null genotype in ESRD patients was found to be independent predictor of overall and cardiovascular mortality. However, after false discovery rate and Bonferroni corrections this effect was lost. The borderline effect modification by wild-type GSTA1*A/*A genotype on associations between GSTM1-null and analyzed outcomes was found only for death from stroke. Homozygous carriers of combined GSTM1*0/GSTA1*A genotype exhibited significantly shorter time to death of stroke or MI in comparison with carriers of either GSTM1-active or at least one GSTA1*B gene variant. The best survival rate regarding cardiovascular outcome was found for ESRD patients with combined GSTM1-active and mutant GSTA1*B/*B genotype. Combined GSTM1*0/GSTA1*A genotypes might be considered as genetic markers for cardiovascular death risk in ESRD patients, which may permit targeting of preventive and early intervention.

  10. Molecular identification and genotyping of Trypanosoma cruzi DNA in autochthonous Chagas disease patients from Texas, USA.

    Science.gov (United States)

    Garcia, Melissa N; Burroughs, Hadley; Gorchakov, Rodion; Gunter, Sarah M; Dumonteil, Eric; Murray, Kristy O; Herrera, Claudia P

    2017-04-01

    The parasitic protozoan Trypanosoma cruzi, the causative agent of Chagas disease, is widely distributed throughout the Americas, from the southern United States (US) to northern Argentina, and infects at least 6 million people in endemic areas. Much remains unknown about the dynamics of T. cruzi transmission among mammals and triatomine vectors in sylvatic and peridomestic eco-epidemiological cycles, as well as of the risk of transmission to humans in the US. Identification of T. cruzi DTUs among locally-acquired cases is necessary for enhancing our diagnostic and clinical prognostic capacities, as well as to understand parasite transmission cycles. Blood samples from a cohort of 15 confirmed locally-acquired Chagas disease patients from Texas were used for genotyping T. cruzi. Conventional PCR using primers specific for the minicircle variable region of the kinetoplastid DNA (kDNA) and the highly repetitive genomic satellite DNA (satDNA) confirmed the presence of T. cruzi in 12/15 patients. Genotyping was based on the amplification of the intergenic region of the miniexon gene of T. cruzi and sequencing. Sequences were analyzed by BLAST and phylogenetic analysis by Maximum Likelihood method allowed the identification of non-TcI DTUs infection in six patients, which corresponded to DTUs TcII, TcV or TcVI, but not to TcIII or TcIV. Two of these six patients were also infected with a TcI DTU, indicating mixed infections in those individuals. Electrocardiographic abnormalities were seen among patients with single non-TcI and mixed infections of non-TcI and TcI DTUs. Our results indicate a greater diversity of T. cruzi DTUs circulating among autochthonous human Chagas disease cases in the southern US, including for the first time DTUs from the TcII-TcV-TcVI group. Furthermore, the DTUs infecting human patients in the US are capable of causing Chagasic cardiac disease, highlighting the importance of parasite detection in the population. Copyright © 2017 Elsevier B

  11. Investigation of an Outbreak of Diphtheria in Dabela Village of Amirgagh Taluka and CHC, Banaskantha, Gujarat

    Directory of Open Access Journals (Sweden)

    Niti Talsania, Jignesh Chauhan, Himanshu Nayak, Chintul Shah, Krunal Modi, Jaydeep devaliya

    2011-01-01

    Full Text Available As outbreak of diphtheria reflects the impact of immunization outbreak investigation was carried out to assess the diphtheria outbreak pattern and case fatality rate in Dabela Village of Amirgagh Taluka and CHC, District, Banaskantha, Gujarat in 2007. Population stabilization, poverty alleviation, lifestyle modification, surveillance and control of communicable and non-communicable diseases constitute the major challenges demanding urgent attention in the future. Vaccine was efficacious among those who received >4 doses. The proportion of the population receiving boosters was low, especially among Muslims. We recommend increasing booster dose coverage. We investigated epidemic to 1 describe the epidemiology of diphtheria in terms of time, place, and person; 2 estimate vaccine coverage; and 3 to do SWOT analysis in Immunization services.4 To suggest successful vaccination.

  12. Data on genotypic distribution and linkage disequilibrium of several ANRIL polymorphisms in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    A. Arbiol-Roca

    2017-04-01

    Full Text Available A long non-coding RNA called ANRIL located on chromosome 9p21.3 has been identified as a novel genetic factor associated with cardiovascular disease. Investigation of several single nucleotide polymorphisms (SNPs of Noncoding Antisense RNA in the INK4 Locus (ANRIL gene are of particular interest. This article reports data related to the research article entitled: “Association of ANRIL gene polymorphisms with major adverse cardiovascular events in hemodialysis patients” (Arbiol-Roca et al. [1]. Data presented show the genotypic distribution of four selected ANRIL SNPs: rs10757278, rs4977574, rs10757274 and rs6475606 in a cohort constituted by 284 hemodialysis patients. This article analyzes the Hardy-Weinberg disequilibrium of each studied SNP, and the linkage disequilibrium between them.

  13. Dental management of amelogenesis imperfecta patients: a primer on genotype-phenotype correlations.

    Science.gov (United States)

    Ng, F K; Messer, L B

    2009-01-01

    Amelogenesis imperfecta (AI) represents a group of hereditary conditions which affects enamel formation in the primary and permanent dentitions. Mutations in genes critical for amelogenesis result in diverse phenotypes characterized by variably thin and/or defective enamel. To date, mutations in 5 genes are known to cause AI in humans. Understanding the molecular etiologies and associated inheritance patterns can assist in the early diagnosis of this condition. Recognition of genotype-phenotype correlations will allow clinicians to guide genetic testing and select appropriate management strategies for patients who express different phenotypes. The purpose of this paper was to provide a narrative review of the current literature on amelogenesis imperfecta, particularly regarding recent advances in the identification of candidate genes and the patterns of inheritance.

  14. Detection and genotyping of enteroviruses in cerebrospinal fluid in patients in Victoria, Australia, 2007-2013.

    Science.gov (United States)

    Papadakis, Georgina; Chibo, Doris; Druce, Julian; Catton, Michael; Birch, Chris

    2014-09-01

    Genotyping by VP1 fragment polymerase chain reaction (PCR) and nucleic acid sequencing to detect enterovirus (EV) genotypes was performed directly on 729 EV PCR positive cerebrospinal fluid (CSF) samples collected between 2007 and 2012 from Victorian hospital inpatients. The overall genotype identification rate from CSF-positive material was 43%. The four most common genotypes identified were Echovirus 6 (24%), Echovirus 30 (17%), Echovirus 25 (10%), and Coxsackievirus A9 (10%), together comprising 61% of all EVs typed. The seasonal distribution of all EVs identified followed the recognized pattern of mainly summer epidemics. Three of the four predominant genotypes were present in each of the 6 years in which the study was conducted, with 20 other EV genotypes also detected, often in only a single year. Genotyping of EVs directly in CSF is faster, simpler and more sensitive than traditional virus neutralization assays performed on EV positive samples. © 2014 Wiley Periodicals, Inc.

  15. The Matchmaker Exchange API: automating patient matching through the exchange of structured phenotypic and genotypic profiles.

    Science.gov (United States)

    Buske, Orion J; Schiettecatte, François; Hutton, Benjamin; Dumitriu, Sergiu; Misyura, Andriy; Huang, Lijia; Hartley, Taila; Girdea, Marta; Sobreira, Nara; Mungall, Chris; Brudno, Michael

    2015-10-01

    Despite the increasing prevalence of clinical sequencing, the difficulty of identifying additional affected families is a key obstacle to solving many rare diseases. There may only be a handful of similar patients worldwide, and their data may be stored in diverse clinical and research databases. Computational methods are necessary to enable finding similar patients across the growing number of patient repositories and registries. We present the Matchmaker Exchange Application Programming Interface (MME API), a protocol and data format for exchanging phenotype and genotype profiles to enable matchmaking among patient databases, facilitate the identification of additional cohorts, and increase the rate with which rare diseases can be researched and diagnosed. We designed the API to be straightforward and flexible in order to simplify its adoption on a large number of data types and workflows. We also provide a public test data set, curated from the literature, to facilitate implementation of the API and development of new matching algorithms. The initial version of the API has been successfully implemented by three members of the Matchmaker Exchange and was immediately able to reproduce previously identified matches and generate several new leads currently being validated. The API is available at https://github.com/ga4gh/mme-apis.

  16. Hepatitis B virus genotype E detected in Brazil in an African patient who is a frequent traveler

    Directory of Open Access Journals (Sweden)

    R Sitnik

    2007-12-01

    Full Text Available Genotype E of hepatitis B virus (HBV has not been described in Brazil and is found mainly in Africa. Genotype A is the most prevalent in Brazil, and genotypes B, C, D, and F have already been reported. We report here an HBV genotype E-infected patient and some characterization of surface (S protein, DNA polymerase (P and precore/core (preC/C coding regions based on the viral genome. The patient is a 31-year-old black man with chronic hepatitis B who was born and raised in Angola. He has been followed by a hepatologist in São Paulo, Brazil, since November 2003, and he is a frequent traveler to Latin America, Africa, and Europe. In 2003, he was diagnosed with HBV infection and started treatment with lamivudine with the later addition of adefovir dipivoxil. No known risk factor was identified. Serologically, he is HBsAg and anti-HBe positive, but HBeAg and anti-HBs negative. DNA sequence analysis of the S/P region confirmed that this patient is infected with genotype E, subtype ayw4. The preC/C region showed G1896A and G1899A mutations but no mutations in the basal core promoter. Nucleotide substitutions common in genotype E were also observed (C1772, T1858 and A1757. Although this is not an autochthonous case and there is no evidence of further spread, the description of this case in Brazil highlights the current risk of viral genotypes spreading with unprecedented speed due to constant travel around the world.

  17. An alternative Cattell-Horn-Carroll (CHC) factor structure of the WAIS-IV: age invariance of an alternative model for ages 70-90.

    Science.gov (United States)

    Niileksela, Christopher R; Reynolds, Matthew R; Kaufman, Alan S

    2013-06-01

    The Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV) is by the far the most popular intelligence test for the assessment of adults in clinical and neuropsychological practice. Despite a number of studies examining the factor structure of the WAIS-IV from a Cattell-Horn-Carroll (CHC) perspective (Benson, Hulac, & Kranzler, 2010; Ward, Bergman, & Hebert, 2012), a CHC interpretation of the WAIS-IV for individuals ages 70 and above has been absent from the literature. The exclusion of individuals ages 70 and above in previous research is likely due to the absence of several key supplemental subtests used to create a full CHC model. We provide an alternative five-factor CHC model of the WAIS-IV which includes only the subtests administered to individuals ages 70 and above in the standardization sample. Our results show (a) the alternative CHC model fits the data well; (b) this alternative CHC model met criteria for partial strict measurement invariance across the life span (only Similarities showed noninvariance) using strict criteria; (c) the five factors for ages 70-90 measure the same five CHC broad abilities identified in previous analyses reported for ages 16-69; and (d) the five-factor CHC solution for ages 70-90 is valid for the entire WAIS-IV age range and can be used whenever examiners administer the core battery but opt not to administer supplemental subtests. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  18. Quantitation of HBsAg predicts response to entecavir therapy in HBV genotype C patients

    Institute of Scientific and Technical Information of China (English)

    Etsuro Orito; Kei Fujiwara; Hiroshi Kanie; Tesshin Ban; Tomonori Yamada; Katsumi Hayashi

    2012-01-01

    AIM:To analysis the factors that predict the response to entecavir therapy in chronic hepatitis patients with hepatitis B virus (HBV) genotype C.METHODS:Fifty patients [hepatitis B e antigen (HBeAg)-negative:HBeAg-positive =26:24] with HBV genotype C,who received na(i)ve entecavir therapy for > 2 years,were analyzed.Patients who showed HBV DNA levels ≥3.0 log viral copies/mL after 2 years of entecavir therapy were designated as slow-responders,while those that showed < 3.0 log copies/mL were termed rapidresponders.Quantitative hepatitis B surface antigen (HBsAg) levels (qHBsAg) were determined by the Architect HBsAg QT immunoassay.Hepatitis B core-related antigen was detected by enzyme immunoassay.Pre-C and Core promoter mutations were determined using by polymerase chain reaction (PCR).Drug-resistance mutations were detected by the PCR-Invader method.RESULTS:At year 2,HBV DNA levels in all patients in the HBeAg-negative group were < 3.0 log copies/mL.In contrast,in the HBeAg-positive group,41.7% were slow-responders,while 58.3% were rapid-responders.No entecavir-resistant mutants were detected in the slow-responders.When the pretreatment factors were compared between the slow-and rapid-responders;the median qHBsAg in the slow-responders was 4.57log IU/mL,compared with 3.63 log IU/mL in the rapidresponders (P < 0.01).When the pretreatment factors predictive of HBV DNA-negative status at year 2 in all 50 patients were analyzed,HBeAg-negative status,low HBV DNA levels,and low qHBsAg levels were significant (P < 0.01).Multivariate analysis revealed that the low qHBsAg level was the most significant predictive factor (P =0.03).CONCLUSION:Quantitation of HBsAg could be a useful indicator to predict response to entecavir therapy.

  19. Algorithmic approach to high-throughput molecular screening for alpha interferon-resistant genotypes in hepatitis C patients.

    Science.gov (United States)

    Sreevatsan, S; Bookout, J B; Ringpis, F M; Pottathil, M R; Marshall, D J; De Arruda, M; Murvine, C; Fors, L; Pottathil, R M; Barathur, R R

    1998-07-01

    This study was designed to analyze the feasibility and validity of using Cleavase Fragment Length Polymorphism (CFLP) analysis as an alternative to DNA sequencing for high-throughput screening of hepatitis C virus (HCV) genotypes in a high-volume molecular pathology laboratory setting. By using a 244-bp amplicon from the 5' untranslated region of the HCV genome, 61 clinical samples received for HCV reverse transcription-PCR (RT-PCR) were genotyped by this method. The genotype frequencies assigned by the CFLP method were 44.3% for type 1a, 26.2% for 1b, 13.1% for type 2b, and 5% type 3a. The results obtained by nucleotide sequence analysis provided 100% concordance with those obtained by CFLP analysis at the major genotype level, with resolvable differences as to subtype designations for five samples. CFLP analysis-derived HCV genotype frequencies also concurred with the national estimates (N. N. Zein et al., Ann. Intern. Med. 125:634-639, 1996). Reanalysis of 42 of these samples in parallel in a different research laboratory reproduced the CFLP fingerprints for 100% of the samples. Similarly, the major subtype designations for 19 samples subjected to different incubation temperature-time conditions were also 100% reproducible. Comparative cost analysis for genotyping of HCV by line probe assay, CFLP analysis, and automated DNA sequencing indicated that the average cost per amplicon was lowest for CFLP analysis, at $20 (direct costs). On the basis of these findings we propose that CFLP analysis is a robust, sensitive, specific, and an economical method for large-scale screening of HCV-infected patients for alpha interferon-resistant HCV genotypes. The paper describes an algorithm that uses as a reflex test the RT-PCR-based qualitative screening of samples for HCV detection and also addresses genotypes that are ambiguous.

  20. A visit to CHC of a larger number of women. JICA Reproductive Health Project. Yen Than district.

    Science.gov (United States)

    Trinh Xuan Hong

    1999-01-01

    The situation of the Bac Than Commune Health Center (CHC) in Yen Than District, Vietnam is reported. Promotion of education, improvement in health care, and economic development are the strategic programs for improving the commune people's standard of living. For the promotion of education, the CHC upgraded educational facilities and trained teachers on the use of efficient teaching methods. In order to generate a bigger income, efforts are exerted to promote the development of agriculture by producing agricultural products that are popular and sell high in the market. These activities have yielded positive results. Many students are doing well in their classes and are attending universities and the per capita yield of products has increased. For the improvement in health care, the Japan International Cooperation Agency Reproductive Health project has contributed much to the CHC. The three activities observed were 1) implementation of information, education and communication activities; 2) training of health staff members; and 3) renovation of the health facility. Such improvements have led to a visit to CHC of a larger number of women for gynecological examinations and prenatal check-ups and safe delivery.

  1. The Role of Cattell-Horn-Carroll (CHC) Cognitive Abilities in Predicting Writing Achievement during the School-Age Years

    Science.gov (United States)

    Cormier, Damien C.; Bulut, Okan; McGrew, Kevin S.; Frison, Jessica

    2016-01-01

    Writing is a complex academic task--it involves numerous mental processes. Given the necessity for developing writing skills from elementary to secondary school, this study aimed to investigate the role of broad cognitive abilities derived from the Cattell-Horn-Carroll (CHC) theory of intelligence in predicting skills associated with writing…

  2. Impact of Interleukin-28B Polymorphism on Response to Treatment in Chinese Hepatitis C Patients

    Institute of Scientific and Technical Information of China (English)

    Lü Jian-nan; WANG Song; XU Yan; ZHANG Man-hua; SIQING Tunala; JI Shang-wei; JIAO Jian; WANG Xu; WANG Jiang-bin

    2012-01-01

    The candidate polymorphism rs12979860 of interleukin 28B(IL28B) gene was genotyped by means of polymerase chain reaction(PCR) amplification and direct PCR sequencing,and then the role of this single nucleotide polymorphism(SNP) in the response to the treatment of 172 Chinese patients with hepatitis C virus(HCV) chronic infection was analyzed.The results show that the frequencies of major homozygotes(CC) and heterozygotes(CT) of rs12979860 were 0.84 and 0.16,respectively,and the minor homozygotes(TT) wasn't found in this cohort.A highly significant association was found between the CC genotype and sustained virological response(SVR) in HCV genotype 1 infected patients(P<0.001) but not in HCV non-genotype 1 infected patients.In addition,a strong association was found between rs12979860 CC genotype and rapid virological response(RVR) in both HCV genotype 1 infected patients(P<0.001) and non-genotype 1 infected patients(P<0.001).Taken together,these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients.Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C(CHC) patients.

  3. Chronic Hepatitis C treatment for genotype 2 or 3 in Brazil: cost effectiveness analysis of peginterferon plus ribavirin as first choice treatment

    Directory of Open Access Journals (Sweden)

    Carine Raquel Blatt

    2014-04-01

    Full Text Available Brazilian Guidelines to HCV treatment (2007 recommended that the first choice treatment for patients with chronic hepatitis C (CHC and genotype 2 or 3 is interferon alpha (IFN plus ribavirin (RBV for 24 weeks. The aim of this study is compare the cost and effectiveness to Hepatitis C treatment in patients with genotype 2 or 3 of peginterferon alpha (PEG as the first choice of treatment within PEG for those that do not respond to IFN. The target population is CHC patients with genotype 2 or 3 in Brazil. The interventions are: PEG-SEC (first IFN plus RBV for 24 weeks, after, for non-responders and relapsers subsequently PEG plus RBV for 48 weeks; PEG-FIRST24 (PEG+RBV for 24 weeks. The type of the study is cost-effectiveness analysis. The data sources are: Effectiveness data from meta-analysis conducted on the Brazilian population. Treatment cost from Brazilian micro costing study is converted into USD (2010. The perspective is the Public Health System. The outcome measurements are Sustained Viral Response (SVR and costs. PEG-FIRST24 (SVR: 87.8%, costs: USD 8,338.27 was more effective and more costly than PEG-SEC (SVR: 79.2%, costs: USD 5,852.99. The sensitivity analyses are: When SVR rates with IFN was less than 30% PEG-FIRST is dominant. On the other hand, when SVR with IFN was more then 75% PEG-SEC is dominant (SVR=88.2% and costs USD $ 3,753.00. PEG-SEC is also dominant when SVR to PEG24 weeks was less than 54%. In the Brazilian context, PEG-FIRST is more effective and more expensive than PEG-SEC. PEG-SEC could be dominant when rates of IFN therapy are higher than 75% or rates of PEG24 therapy are lower than 54%.

  4. Genotypic and functional diversity of phenotypically defined primitive hematopoietic cells in patients with chronic myeloid leukemia.

    Science.gov (United States)

    Sloma, Ivan; Beer, Philip A; Saw, Kyi Min; Chan, Matthew; Leung, Donna; Raghuram, Kamini; Brimacombe, Cedric; Johnston, Bobby; Lambie, Karen; Forrest, Donna; Jiang, Xiaoyan; Eaves, Connie J

    2013-10-01

    Much progress has been made in the management of chronic-phase chronic myeloid leukemia (CP-CML), but there is a continuing imperative to develop curative treatments, predict patient responses to specific modalities, and anticipate disease relapse or progression. These needs underlie continuing interest in methods to detect and quantify the relevant leukemic cells in clinical samples with improved reliability and specificity. We report the results of comparing three methods to enumerate primitive CP-CML cells in the same samples: genotyping CD34(+)38(-) cells directly by fluorescence in situ hybridization, and measuring BCR-ABL1 transcript-genotyped colony-forming cell outputs in either 5-week long-term cultures (LTCs) containing non-engineered mouse fibroblasts or in 6-week LTCs containing mouse fibroblasts engineered to produce human Steel factor, granulocyte colony-stimulating factor, and IL-3. The results demonstrate that the first two methods significantly overestimate the prevalence of primitive CP-CML cells by comparison to the third. In additional studies, we found that CML-CD34(+) cells can repopulate the marrow and spleen of serially transplanted adult NOD/SCID-IL-2Rγ chain-null mice for more than 1 year with an almost exclusive myeloid differentiation in primary and secondary recipients and without evidence of disease progression. These findings underscore the importance of long-term functional in vitro and in vivo endpoints to identify and characterize CP-CML stem cells. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  5. Clinical characteristics of patients with chronic hepatitis B who developed genotypic resistance to entecavir: Real-life experience.

    Science.gov (United States)

    Kim, Hong Joo; Cho, Yong Kyun; Jeon, Woo Kyu; Kim, Byung Ik

    2017-09-05

    Clinical characteristics of patients with chronic hepatitis B (CHB) who developed genotypic resistance to entecavir (ETV) were compared to those without resistance. Two hundred fifty eight CHB patients who underwent ETV treatment in our institution from July 2007 to May 2013 were included. Eight (3.1%) patients developed genotypic resistance to ETV during the follow-up period. The patterns of genotypic resistance to ETV were as follows: L180M + M204V + S202G (n=3); M204I + V173M (n=1); I169V + V173M (n=1); L180M + M204V + V173L (n=1); L180M + M204V + V173L + M250V (n=1); M204I + V214A + P237H (n=1). The cumulative occurrence rates of genotypic resistance to ETV were not significantly different between CHB patients with prior nucleos(t)tide analogues (NA) exposure (NA experienced, n=56) and NA naïve patients (n=202, P=0.823 by log rank comparison). Older age, higher baseline log10hepatitis B virus-deoxynucleic acid (log10HBV-DNA), higher log10HBV-DNA at 3, 6, 12 and 24 months after baseline, and complete virologic response (CVR, undetectable serum HBV-DNA by polymerase chain reaction 6 months after ETV treatment) were significant contributors to the development of genotypic resistance to ETV. Multivariate analyses showed higher log10HBV-DNA 6 months after baseline and absence of CVR were independent and significant contributors to the development of ETV resistance. Clinical characteristics of patients who developed ETV resistance were higher log10HBV-DNA 6 months after baseline and absence of CVR during the ETV treatment.

  6. Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome : a series of 136 patients from the Eurofever Registry

    NARCIS (Netherlands)

    Levy, R.; Gerard, L.; Kuemmerle-Deschner, J.; Lachmann, H. J.; Kone-Paut, I.; Cantarini, L.; Woo, P.; Naselli, A.; Bader-Meunier, B.; Insalaco, A.; AI-Mayoutl, S. M.; Ozen, S.; Hofer, M.; Frenkel, J.; Modesto, C.; Nikishina, I.; Schwarz, T.; Martino, S.; Meini, A.; Quartier, P.; Martini, A.; Ruperto, N.; Neven, B.; Gattorno, M.

    2015-01-01

    Objective To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. Methods A web-based registry retrospectively collected

  7. Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients

    DEFF Research Database (Denmark)

    Hoornaert, Kristien P; Vereecke, Inge; Dewinter, Chantal;

    2010-01-01

    Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation ...

  8. Association of Angiotensin-Converting Enzyme Genotype, Insertion/Deletion Polymorphism and Saphenous Vein Graft Atherosclerosis in Iranian Patients

    Directory of Open Access Journals (Sweden)

    Neda Zeinali

    2015-10-01

    Full Text Available ABSTRACT OBJECTIVE: The aim of this study was to evaluate possible interactions among Angiotensin-I converting enzyme genotype, insertion/deletion polymorphism and atherosclerosis of vein grafts in Iranian patients, and characterize their clinical and demographic profile. METHODS: In this cross-sectional study, patients who underwent coronary artery bypass graft surgery more than five years ago, were included for angiographic analysis. Atherosclerosis was determined by quantitative angiography and adjusted Gensini score. The gene angiotensin converting enzyme I/D polymorphism was detected by polymerase chain reaction. RESULTS: A total of 102 patients participated in this study. Eighty-four patients were male. The frequency distribution of DD, ID and II polymorphism were 23.6%, 62.7% and 13.7% respectively. There were no differences among genotypic groups in age, sex, number of risk factors, number of vein grafts and months since bypass surgery. According to adjusted Gensini score [0.18±0.12 (II vs. 0.11±0.09 (ID and 0.1±0.09 (DD P=0.021] the II genotype was associated with severity of vein graft atherosclerosis. CONCLUSION: Although there are conflicting results about gene angiotensin converting enzyme I/D polymorphism and the degree of venous bypass graft degeneration, this study suggests an association between ACE genotype II and atherosclerosis of saphenous vein grafts, however, large samples considering clinical, demographic and ethnic profile are necessary to confirm these results.

  9. Clinically relevant RHD-CE genotypes in patients with sickle cell disease and in African Brazilian donors

    Science.gov (United States)

    Gaspardi, Ane C.; Sippert, Emília A.; de Macedo, Mayra Dorigan; Pellegrino, Jordão; Costa, Fernando F.; Castilho, Lilian

    2016-01-01

    Background As a consequence of the homology and opposite orientation of RHD and RHCE, numerous gene rearrangements have occurred in Africans and resulted in altered RH alleles that predict partial antigens, contributing to the high rate of Rh alloimmunisation among patients with sickle cell disease (SCD). In this study, we characterised variant RH alleles encoding partial antigens and/or lacking high prevalence antigens in patients with SCD and in African Brazilian donors, in order to support antigen-matched blood for transfusion. Material and methods RH genotypes were determined in 168 DNA samples from SCD patients and 280 DNA samples from African Brazilian donors. Laboratory developed tests, RHD BeadChipTM, RHCE BeadChipTM, cloning and sequencing were used to determine RHD-CE genotypes among patients and African Brazilian blood donors. Results The distributions of RHD and RHCE alleles in donors and patients were similar. We found RHCE variant alleles inherited with altered RHD alleles in 25 out of 168 patients (15%) and in 22 out of 280 (7.8%) African Brazilian donors. The RHD and RHCE allele combinations found in the population studied were: RHD*DAR with RHCE*ceAR; RHD*weak D type 4.2.2 with RHCE*ceAR, RHD*weak D type 4.0 with RHCE*ceVS.01 and RHCE*ceVS.02; RHD*DIIIa with RHCE*ceVS.02. Thirteen patients and six donors had RHD-CE genotypes with homozygous or compound heterozygous alleles predicting partial antigens and/or lacking high prevalence antigens. Eleven patients were alloimmunised to Rh antigens. For six patients with RHD-CE genotypes predicting partial antigens, no donors with similar genotypes were found. Discussion Knowledge of the distribution and prevalence of RH alleles in patients with SCD and donors of African origin may be important for implementing a programme for RH genotype matching in SCD patients with RH variant alleles and clinically significant Rh antibodies. PMID:27177398

  10. Maintenance of Chronic Fatigue Syndrome (CFS in Young CFS Patients Is Associated with the 5-HTTLPR and SNP rs25531 A > G Genotype.

    Directory of Open Access Journals (Sweden)

    Benedicte Meyer

    Full Text Available Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT may be important for the re-uptake of serotonin (5-HT in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S versus long (L 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS. All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12-18 years. Main outcomes were number of steps per day obtained by an accelerometer and disability scored by the Functional Disability Inventory (FDI. Patients with the 5-HTT SS or SLG genotype had a significantly lower number of steps per day than patients with the 5-HTT LALG, SLA or LALA genotype. Patients with the 5-HTT SS or SLG genotype also had a significantly higher FDI score than patients with the 5-HTT LALG, SLA or LALA genotype. Thus, CFS patients with the 5-HTT SS or SLG genotype had worse 30 weeks outcome than CFS patients with the 5-HTT LALG, SLA or LALA genotype. The present study suggests that the 5-HTT genotype may be a factor that contributes to maintenance of CFS.

  11. Hepatocellular Carcinoma in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Dmitry Konstantinov

    2016-09-01

    Full Text Available The purpose of the study was to examine the clinical and epidemiological data in patients with chronic hepatitis C (CHC and hepatocellular carcinoma (HCC before they sought specialized medical care. The study included 92 patients with CHC. All patients were divided into 2 groups: Group 1 consisted of CHC patients with HCC (n=45, and Group 2 (n=47 consisted of CHC patients without HCC. With the development of HCC in CHC patients, clinical manifestations were absent only in 2.2% of patients. Determining factors in HCC development are male sex, mature age, the maintained HCV replication, moderate and severe fibrosis, disease duration of more than 10 years, and the lack of effect of antiviral treatment.

  12. Genotyping of fanconi anemia patients by whole exome sequencing: advantages and challenges.

    Directory of Open Access Journals (Sweden)

    Kerstin Knies

    Full Text Available Fanconi anemia (FA is a rare genomic instability syndrome. Disease-causing are biallelic mutations in any one of at least 15 genes encoding members of the FA/BRCA pathway of DNA-interstrand crosslink repair. Patients are diagnosed based upon phenotypical manifestations and the diagnosis of FA is confirmed by the hypersensitivity of cells to DNA interstrand crosslinking agents. Customary molecular diagnostics has become increasingly cumbersome, time-consuming and expensive the more FA genes have been identified. We performed Whole Exome Sequencing (WES in four FA patients in order to investigate the potential of this method for FA genotyping. In search of an optimal WES methodology we explored different enrichment and sequencing techniques. In each case we were able to identify the pathogenic mutations so that WES provided both, complementation group assignment and mutation detection in a single approach. The mutations included homozygous and heterozygous single base pair substitutions and a two-base-pair duplication in FANCJ, -D1, or -D2. Different WES strategies had no critical influence on the individual outcome. However, database errors and in particular pseudogenes impose obstacles that may prevent correct data perception and interpretation, and thus cause pitfalls. With these difficulties in mind, our results show that WES is a valuable tool for the molecular diagnosis of FA and a sufficiently safe technique, capable of engaging increasingly in competition with classical genetic approaches.

  13. Emergence of occult minority genotype 2b hepatitis C infection in an HIV-1-co-infected patient treated for genotype 5a HCV infection with 48 weeks of pegylated-interferon-alpha 2b and ribavirin.

    Science.gov (United States)

    Buckton, A J; Kulasegaram, R; Ngui, S L; Fisher, M; James, R; Rangarajan, S; Teo, C G

    2007-09-01

    An HIV-1/hepatitis C virus (HCV) co-infected patient with haemophilia received a 48-week course of pegylated interferon-alpha-2b and ribavirin therapy for genotype 5a HCV infection. Virological response was achieved at week 24. At the end of treatment, HCV RNA in serum was detected and identified to belong to genotype 2b, rather than genotype 5a. A sensitive method for identifying minority HCV genotypes in pre-treatment serum showed genotype 2b HCV carriage prior to treatment. Sequencing the interferon sensitivity-determining region of the HCV NS5A gene obtained from pre-, intra- and post-treatment sera revealed emergence of quasispecies bearing R-->K and M-->A/T mutations at codons 2222 and 2223, respectively. Occult presence of minority HCV subpopulations and their acquisition of mutations following therapy can result in poor treatment outcome.

  14. CYP2C9 polymorphism in patients with epilepsy: genotypic frequency analyzes andphenytoin adverse reactions correlation

    Directory of Open Access Journals (Sweden)

    Carlos Alexandre Twardowschy

    2011-04-01

    Full Text Available OBJECTIVE: CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect therapeutic outcome during treatment. The distribution of variant CYP2C9 alleles and prevalence of phenytoin adverse reactions were hereby investigated in a population of patients diagnosed with epilepsy. METHOD: Allele-specific PCR analysis was carried out in order to determine frequencies of the two most common variant alleles, CYP2C9*2 and CYP2C9*3 in genomic DNA isolated from 100 epileptic patients. We also analyzed the frequency of phenytoin adverse reactions among those different genotypes groups. The data was presented as mean±standard deviation. RESULTS: The mean age at enrollment was 39.6±10.3 years (range, 17-72 years and duration of epilepsy was 26.5±11.9 years (range 3-48 years. The mean age at epilepsy onset was 13.1±12.4 years (range, 1 month-62 years. Frequencies of CYP2C9*1 (84%, CYP2C9*2 (9% and CYP2C9*3 (7% were similar to other published reports. Phenytoin adverse reactions were usually mild and occurred in 15% patients, without correlation with the CYP2C9 polymorphism (p=0.34. CONCLUSION: Our findings indicate an overall similar distribution of the CYP2C9 alleles in a population of patients diagnosed with epilepsy in the South of Brazil, compared to other samples. This sample of phenytoin users showed no drug related adverse reactions and CYP2C9 allele type correlation. The role of CYP2C9 polymorphism influence on phenytoin adverse reaction remains to be determined since some literature evidence and our data found negative results.

  15. HLA-DRB genotype and specific IgE responses in patients with allergies to penicillins

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.Methods Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction. Some (113 patients and 87 healthy control subjects) were chosen from all subjects to type for HLA-DRB alleles by sequence specific primer-polymerase chain reaction.Results Compared with control subjects, a significantly increased frequency of DR9 was present in 77 patients with allergic reactions, with immediate hypersensitive reaction and with urticaria (P = 0.011; P = 0.019; P = 0.005 respectively). Conversely, a significantly decreased frequency of DR14.1 was found in 80 patients with positive IgE antibodies, with immediate reaction and with urticaria compared with control group (P = 0.024; P = 0.038; P = 0.038). A possible excess of HLA-DR17 was found in subjects who were responsive to benzylpenicilloyl compared with those were not (χ2 = 5.134, P = 0.023), and of HLA-DR4 was found in subjects responsive to phenoxomethylpenicillanyl (PVA, χ2 = 4.057, P = 0.044).Conclusion HLA-DRB gene may be involved in allergy to penicillins through modulating specific serum IgE to penicillins.

  16. Base excision repair pathway: PARP1 genotypes as modulators of therapy response in cervical cancer patients.

    Science.gov (United States)

    Nogueira, Augusto; Assis, Joana; Faustino, Ilda; Pereira, Deolinda; Catarino, Raquel; Medeiros, Rui

    2017-02-01

    Genetic polymorphisms in genes of the base excision repair (BER) pathway appear to modulate the therapy response of cancer patients. PARP1 protein recognizes the DNA strand damage and facilitates the subsequent recruitment of BER proteins. Few studies have reported an association between PARP1 Val762Ala polymorphism (rs1136410) and cancer therapy response. The purpose of our study was to determine whether PARP1 Val762Ala polymorphism have prognostic value in patients with cervical cancer. Two hundred and sixty adult patients, with histologically confirmed cervical cancer, at FIGO-stages IB2-IVA, primarily treated with concurrent chemotherapy (cisplatin) and radiotherapy. Overall survival (OS) and disease-free survival (DFS) were the primary end points of the analysis. The PARP1 Val762Ala genetic variants were analyzed by allelic discrimination by real-time PCR. We observed that peri- and postmenopausal women carrying the C-allele present a statistically significant lower OS and DFS (log-rank test, p = 0.008 and p = 0.006, respectively) among those with early stage cervical cancer. Cox regression analysis confirmed these results, after adjustment for other prognostic factors (for OS: HR, 3.70; 95%CI, 1.32-10.38; p = 0.013 and for DFS: HR, 3.97; 95%CI, 1.59-9.93; p = 0.003). This is the first study evaluating the effect of PARP1 Val762Ala polymorphism in treatment response in cervical cancer patients. PARP1 genotypes may contribute as an independent prognostic factor in cervical cancer, being useful in predicting the clinical outcome.

  17. Relationship between Genotypes Sult1a2 and Cyp2d6 and Tamoxifen Metabolism in Breast Cancer Patients

    Science.gov (United States)

    Fernández-Santander, Ana; Gaibar, María; Novillo, Apolonia; Romero-Lorca, Alicia; Rubio, Margarita; Chicharro, Luis Miguel; Tejerina, Armando; Bandrés, Fernando

    2013-01-01

    Tamoxifen is a pro-drug widely used in breast cancer patients to prevent tumor recurrence. Prior work has revealed a role of cytochrome and sulfotransferase enzymes in tamoxifen metabolism. In this descriptive study, correlations were examined between concentrations of tamoxifen metabolites and genotypes for CYP2D6, CYP3A4, CYP3A5, SULT1A1, SULT1A2 and SULT1E1 in 135 patients with estrogen receptor-positive breast cancer. Patients were genotyped using the Roche-AmpliChip® CYP450 Test, and Real-Time and conventional PCR-RFLP. Plasma tamoxifen, 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen, endoxifen and tamoxifen-N-oxide were isolated and quantified using a high-pressure liquid chromatography-tandem mass spectrometry system. Significantly higher endoxifen levels were detected in patients with the wt/wt CYP2D6 compared to the v/v CYP2D6 genotype (p<0.001). No differences were detected in the remaining tamoxifen metabolites among CYP2D6 genotypes. Patients featuring the SULT1A2*2 and SULT1A2*3 alleles showed significantly higher plasma levels of 4-hydroxy-tamoxifen and endoxifen (p = 0.025 and p = 0.006, respectively), as likely substrates of the SULT1A2 enzyme. Our observations indicate that besides the CYP2D6 genotype leading to tamoxifen conversion to potent hydroxylated metabolites in a manner consistent with a gene-dose effect, SULT1A2 also seems to play a role in maintaining optimal levels of both 4-hydroxy-tamoxifen and endoxifen. PMID:23922954

  18. Relationship between genotypes Sult1a2 and Cyp2d6 and tamoxifen metabolism in breast cancer patients.

    Science.gov (United States)

    Fernández-Santander, Ana; Gaibar, María; Novillo, Apolonia; Romero-Lorca, Alicia; Rubio, Margarita; Chicharro, Luis Miguel; Tejerina, Armando; Bandrés, Fernando

    2013-01-01

    Tamoxifen is a pro-drug widely used in breast cancer patients to prevent tumor recurrence. Prior work has revealed a role of cytochrome and sulfotransferase enzymes in tamoxifen metabolism. In this descriptive study, correlations were examined between concentrations of tamoxifen metabolites and genotypes for CYP2D6, CYP3A4, CYP3A5, SULT1A1, SULT1A2 and SULT1E1 in 135 patients with estrogen receptor-positive breast cancer. Patients were genotyped using the Roche-AmpliChip® CYP450 Test, and Real-Time and conventional PCR-RFLP. Plasma tamoxifen, 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen, endoxifen and tamoxifen-N-oxide were isolated and quantified using a high-pressure liquid chromatography-tandem mass spectrometry system. Significantly higher endoxifen levels were detected in patients with the wt/wt CYP2D6 compared to the v/v CYP2D6 genotype (p<0.001). No differences were detected in the remaining tamoxifen metabolites among CYP2D6 genotypes. Patients featuring the SULT1A2*2 and SULT1A2*3 alleles showed significantly higher plasma levels of 4-hydroxy-tamoxifen and endoxifen (p = 0.025 and p = 0.006, respectively), as likely substrates of the SULT1A2 enzyme. Our observations indicate that besides the CYP2D6 genotype leading to tamoxifen conversion to potent hydroxylated metabolites in a manner consistent with a gene-dose effect, SULT1A2 also seems to play a role in maintaining optimal levels of both 4-hydroxy-tamoxifen and endoxifen.

  19. Relationship between genotypes Sult1a2 and Cyp2d6 and tamoxifen metabolism in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Ana Fernández-Santander

    Full Text Available Tamoxifen is a pro-drug widely used in breast cancer patients to prevent tumor recurrence. Prior work has revealed a role of cytochrome and sulfotransferase enzymes in tamoxifen metabolism. In this descriptive study, correlations were examined between concentrations of tamoxifen metabolites and genotypes for CYP2D6, CYP3A4, CYP3A5, SULT1A1, SULT1A2 and SULT1E1 in 135 patients with estrogen receptor-positive breast cancer. Patients were genotyped using the Roche-AmpliChip® CYP450 Test, and Real-Time and conventional PCR-RFLP. Plasma tamoxifen, 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen, endoxifen and tamoxifen-N-oxide were isolated and quantified using a high-pressure liquid chromatography-tandem mass spectrometry system. Significantly higher endoxifen levels were detected in patients with the wt/wt CYP2D6 compared to the v/v CYP2D6 genotype (p<0.001. No differences were detected in the remaining tamoxifen metabolites among CYP2D6 genotypes. Patients featuring the SULT1A2*2 and SULT1A2*3 alleles showed significantly higher plasma levels of 4-hydroxy-tamoxifen and endoxifen (p = 0.025 and p = 0.006, respectively, as likely substrates of the SULT1A2 enzyme. Our observations indicate that besides the CYP2D6 genotype leading to tamoxifen conversion to potent hydroxylated metabolites in a manner consistent with a gene-dose effect, SULT1A2 also seems to play a role in maintaining optimal levels of both 4-hydroxy-tamoxifen and endoxifen.

  20. UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study.

    NARCIS (Netherlands)

    Kweekel, D.M.; Gelderblom, H.; Straaten, T Van der; Antonini, N.F.; Punt, C.J.A.; Guchelaar, H.J.

    2008-01-01

    The aim of the study was to investigate the associations between UGT1A1(*)28 genotype and (1) response rates, (2) febrile neutropenia and (3) dose intensity in patients with metastatic colorectal cancer treated with irinotecan. UGT1A1(*)28 genotype was determined in 218 patients receiving irinotecan

  1. Moderator effect of CYP2B6 genotype in HIV-1 patients with tuberculosis treated with rifampicin and efavirenz

    Directory of Open Access Journals (Sweden)

    C De la Calle

    2012-11-01

    Full Text Available Efavirenz (EFV is the preferred non-nucleoside reverse transcriptase inhibitor component of the ARV regimen in HIV-TB patients. Concomitant use of EFV with rifampicin (RIF, an important component of first-line tuberculosis treatment, induces various hepatic cytochrome P450 enzymes and is known to decrease EFV plasma concentrations in healthy volunteers and HIV-1 patients and EFV plasma concentrations below 1,000 µg/mL have been associated with an increased risk of virological failure [1]. Moreover, previous studies have shown that inter-individual variability in EFV plasma concentrations are associated with the presence of allelic variants in CYP2B6 gene. Carriers of the T allele of polymorphism 516 G>T are reported to be associated with slower EFV oral clearance. The aim of our study was to determine the influence of CYP2B6 genotype in EFV levels in HIV patients with TB treated with RIF. Four HIV patients who started ARV treatment concomitantly with TB treatment were analyzed. These patients started a regimen based on EFV at doses higher than standard due to RIF interaction. Viral load, CD4+ cell count and plasma levels of EFV in plasma were measured at each visit, and genotyping for CYP2B6 (516G>T polymorphism were performed. The self-reported rates of adherence to HAART were very high. One patient, who had TT genotype, required progressive dose reduction by toxic levels (Cmin: 20 µg/mL and effects on the central nervous system. Dose was adjusted to 600 mg qd despite treatment with RIF, and he required even lower doses after completion of TB treatment, 400 mg qd. Two other patients with non-mutated genotype (GG required dose escalation up to 1000 mg qd to achieve minimum recommended EFV concentrations between 1 and 4 µg/mL. All of them achieved virological suppression at six months. The fourth patient, who had non-mutated genotype, required dose increases for several months until dose adjustment. He needed 1600 mg qd during treatment with

  2. Mutation frequency and genotype/phenotype correlation among phenylketonuria patients from Georgia

    Energy Technology Data Exchange (ETDEWEB)

    Woo, S.L.C.; Martinez, D.; Kuozmine, A. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH). To determine the molecular basis of PKU in the state of Georgia, thirty-five Georgian PKU patients representing sixty independent alleles were examined by a combination of DGGE and direct sequence analysis. At present, this approach has led to the identification of 55/60 or about 92% of all mutant alleles. The relatively high frequencies of mutations common to the British Isles (R408W, I65T and L348V) are compatible with 1990 census data showing that 34% of the general Georgian population claim Irish, English or Scottish ancestors. Three new mutations, E76A (1/60), R241L (2/60), and R400R (2/60), were also detected in this study. Although the nucleotide substitution in codon 400 (AGG{r_arrow}CGG) did not change the amino acid sequence, it was the only base change detected in a scan of all 13 exons of two independent alleles. Since codon 400 is split between exons 11 and 12, this change may exert some effect on splicing, as has previously been seen in the PAH gene for the silent mutation Q304Q and the nonsense mutation Y356X, each of which effect codons immediately adjacent to splicing signals. This hypothesis remains to be tested by expression analysis or studies of ectopic transcripts. The remaining 19 characterized alleles contained one of 15 previously identified mutations. Twenty-five of the thirty non-related patients examined in this study were completely genotyped, and there was a strong correlation between mutant PAH genotype, PAH activity predicted from in vitro expression studies where known, and PKU or HPA phenotype. For mutations not yet studied by expression analysis, this correlation suggests that L213P, R241L, Y277D may drastically reduce residual PAH activity while F39L and E76A may retain significant amounts of PAH activity.

  3. GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients.

    Science.gov (United States)

    Marlin, Sandrine; Feldmann, Delphine; Blons, Hélène; Loundon, Natalie; Rouillon, Isabelle; Albert, Sébastien; Chauvin, Pierre; Garabédian, Eréa-Noël; Couderc, Rémy; Odent, Sylvie; Joannard, Alain; Schmerber, Sébastien; Delobel, Bruno; Leman, Jacques; Journel, Hubert; Catros, Hélène; Lemarechal, Cédric; Dollfus, Hélène; Eliot, Marie-Madeleine; Delaunoy, Jean-Louis; David, Albert; Calais, Catherine; Drouin-Garraud, Valérie; Obstoy, Marie-Françoise; Goizet, Cyril; Duriez, Françoise; Fellmann, Florence; Hélias, Jocelyne; Vigneron, Jacqueline; Montaut, Bettina; Matin-Coignard, Dominique; Faivre, Laurence; Baumann, Clarisse; Lewin, Patricia; Petit, Christine; Denoyelle, Françoise

    2005-06-01

    To analyze the clinical features of hearing impairment and to search for correlations with the genotype in patients with DFNB1. Case series. Collaborative study in referral centers, institutional practice. Patients A total of 256 hearing-impaired patients selected on the basis of the presence of biallelic mutations in GJB2 or the association of 1 GJB2 mutation with the GJB6 deletion (GJB6-D13S1830)del. The prevalence of GJB2 mutations and the GJB6 deletion and audiometric phenotypes related to the most frequent genotypes. Twenty-nine different GJB2 mutations were identified. Allelic frequency of 35delG was 69%, and the other common mutations, 313del14, E47X, Q57X, and L90P, accounted for 2.6% to 2.9% of the variants. Concerning GJB6, (GJB6-D13S1830)del accounted for 5% of all mutated alleles and was observed in 25 of 93 compound heterozygous patients. Three novel GJB2 mutations, 355del9, V95M, and 573delCA, were identified. Hearing impairment was frequently less severe in compound heterozygotes 35delG/L90P and 35delG/N206S than in 35delG homozygotes. Moderate or mild hearing impairment was more frequent in patients with 1 or 2 noninactivating mutations than in patients with 2 inactivating mutations. Of 93 patients, hearing loss was stable in 73, progressive in 21, and fluctuant in 2. Progressive hearing loss was more frequent in patients with 1 or 2 noninactivating mutations than in those with 2 inactivating mutations. In 49 families, hearing loss was compared between siblings with similar genotypes, and variability in terms of severity was found in 18 families (37%). Genotype may affect deafness severity, but environmental and other genetic factors may also modulate the severity and evolution of GJB2-GJB6 deafness.

  4. John cunningham (JC) virus genotypes in kidney transplant recipients, rheumatoid arthritis patients and healthy individuals in Isfahan, Iran.

    Science.gov (United States)

    Atyabi, Sayyedeh Rahmaneh; Bouzari, Majid; Kardi, Mohammad Taghi

    2017-02-01

    In healthy individuals John Cunningham virus is latent without any clinical signs, but in the cases of the use of immunosuppressive drugs in graft recipients, autoimmune diseases and also increasing of age, that the immune system is suppressed it may cause disease in reactivation. Progressive multifocal leukoencephalopathy (PML) is the well-known disease caused by the virus. It has also been associated with nephropathy and tumorogensis. At present, based on vp1 capsid gene 7 genotypes have been detected. Genetic variations of JC virus in different geographical areas and the presence of different subtypes is a useful tool for reconstructing of the genetic information of JC virus and understanding of its evolution. The aim of this study was to investigate different genotypes of the JC virus in the urine of 100 kidney transplant recipients, 43 rheumatoid arthritis patients, and 100 healthy individuals as control group in Isfahan. DNA was extracted by phenol-chloroform method and subjected to a nested PCR using specific primer for vp1 capsid gene designed by Oligo 7 software. Fisher's exact test was used for statistical analyses. Using MEGA 6 software the sequences were aligned using Clustal W tool and phylogenetic trees were constructed by neighbor joining method. Thirty-one positive samples were sequenced. Genotypes 1, 3, and 4 of the virus were detected for the first time in Iran. For the first time genotype 3 was reported as the dominant genotype in Iran. For the first time in the world, genotype 4 was detected in rheumatoid arthritis patients. J. Med. Virol. 89:337-344, 2017. © 2016 Wiley Periodicals, Inc.

  5. Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D.

    Science.gov (United States)

    Fouad, Rabab; Abdo, Mahmoud; Eldeen, Hadeel Gamal; Sabry, Dina; Atef, Mira; Ahmed, Rasha; Zayed, Naglaa

    2016-05-01

    Hepatitis delta virus (HDV) usually have an unfavorable clinical outcome in chronic hepatitis B virus (HBV) patients. In Egypt, data about epidemiology, the spectrum of disease, and impact of HDV on HBV infection are rare. To assess the prevalence, clinical and virological characteristics of HDV infection among Egyptian patients with chronic HBV. Adult patients with Hepatitis B surface antigen (HBsAg)-positive were evaluated for the presence of HDV using anti HDV-IgG and HDV RNA by RT-PCR. Routine laboratory investigations, genotypes and subtypes for both HBV and HDV, abdominal sonography, and transient elastography (TE) were done. Liver biopsy was performed only in whenever indicated. One hundred and twenty-one treatment-naïve chronic HBV patients were included. Wild HBV genotype-D2 was found in 98.2% and 81.9% were HBeAg negative. Prevalence of HDV was 8.3% by anti-HDV IgG and 9.9% by RT-PCR. Wild HDV genotype-IIb was reported in 83.3%. HDV infection was more common in males, 90.9% of delta patients were HBeAg negative. Compared to the mono-infected HBV, concomitant HBV/HDV infection was not associated with more derangment in ALT nor advanced stage of fibrosis. 66.7% of HDV patients had significantly lower HBV-DNA level compared to the non-delta patients (P infection was associated with negative HBeAg status, reduction of HBV replication, but neither influenced the clinical course nor increased significant liver damage risk. © 2015 Wiley Periodicals, Inc.

  6. Paraoxonase 1 genotype-phenotype correlation in patients with metabolic syndrome.

    Science.gov (United States)

    Ciumărnean, Lorena; Dronca, Eleonora; Vesa, Ştefan Cristian; Sâmpelean, Dorel; Buzoianu, Anca Dana; Achimaş-Cadariu, Andrei

    2015-01-01

    The aim of the study was to investigate the influence of three single nucleotide polymorphisms (SNPs) (-108C>T, -162A>G and -909G>C) from the promoter region of paraoxonase 1 (PON1) gene on the enzyme activity, in patients with metabolic syndrome (MS). The study group consisted of 61 individuals with MS and the control group of 73 individuals without MS, matched for age and gender. For each individual, clinical and genetic parameters with possible influence on PON1 activities (paraoxonase, arylesterase and lactonase) were measured. PON1 genotyping was performed with PCR-RFLP, using specific primers and restriction enzymes. We found no differences for distribution of PON1 -108C>T, -162A>G and -909G>C polymorphisms, between the two groups (p-NS). The -108C>T and -909G>C polymorphisms were associated with paraoxonase (p=0.03, p=0.006, respectively), arylesterase (p162A>G polymorphism was not associated with paraoxonase (p-NS) or lactonase (p-NS) activities, but influenced the arylesterase activity (p=0.03). PON1 activities were influenced by all three polymorphisms, regardless of the presence of MS.

  7. The rs2071559 AA VEGFR-2 Genotype Frequency Is Significantly Lower in Neovascular Age-Related Macular Degeneration Patients

    Directory of Open Access Journals (Sweden)

    Stefano Lazzeri

    2012-01-01

    Full Text Available In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377 of VEGF-A receptor-2 (VEGFR-2 gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33% in patients with AMD than in the control subjects (34.62%; P=0.0095, chi-square test; Pcorr=0.038; OR=0.42, 95% CI 0.22 to 0.82. In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  8. The rs2071559 AA VEGFR-2 genotype frequency is significantly lower in neovascular age-related macular degeneration patients.

    Science.gov (United States)

    Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Cascio, Elisa; Di Desidero, Teresa; Agosta, Elisa; Canu, Bastianina; Sartini, Maria Sole; Danesi, Romano; Nardi, Marco; Bocci, Guido

    2012-01-01

    In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD) cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377) of VEGF-A receptor-2 (VEGFR-2) gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33%) in patients with AMD than in the control subjects (34.62%; P = 0.0095, chi-square test; P(corr) = 0.038; OR = 0.42, 95% CI 0.22 to 0.82). In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  9. The ABCB1, rs9282564, AG and TT Genotypes and the COMT, rs4680, AA Genotype are Less Frequent in Deceased Patients with Opioid Addiction than in Living Patients with Opioid Addiction.

    Science.gov (United States)

    Christoffersen, Dorte J; Damkier, Per; Feddersen, Søren; Möller, Sören; Thomsen, Jørgen L; Brasch-Andersen, Charlotte; Brøsen, Kim

    2016-10-01

    Sudden death due to acute intoxication occurs frequently in patients with opioid addiction (OA). To examine whether certain genotypes were associated with this, we examined the frequencies of 29 SNPs located in candidate genes related to opioid pharmacology: ABCB1, OPRM1, UGT2B7, CYP3A5, CYP2B6, CYP2C19, CYP2D6, COMT, KCNJ6 and SCN9A in 274 deceased patients with OA (DOA), 309 living patients with OA (LOA) and in 394 healthy volunteers (HV). The main hypothesis of the study was that subjects homozygous for the variant 3435T in ABCB1 (rs1045642) occur more frequently in DOA than in LOA and HV because morphine and methadone more readily cross the blood barrier in these subjects due to a lower efflux transporter activity of the ABCB1 (p-glycoprotein) transporter. Our results did not support this hypothesis, because no statistically significant difference (p = 0.506) in the frequency of the TT genotype of rs1045642 was observed between the DOA, LOA and HV cohorts. However, for another ABCB1 variant, rs9282564, we found that the frequencies of the AG and TT genotypes were 13, 21 and 25% in DOA, LOA and HV, respectively, and after correcting for age, sex and multiple testing, the differences between DOA and LOA were statistically significantly different (p = 0.027). The COMT rs4680 AA genotype frequencies were 25%, 35% and 31% in DOA, LOA and HV, respectively, and the difference between DOA and LOA was also statistically significant (p = 0.0028). In conclusion, this study generated two hypotheses suggesting possible associations of a reduced risk of death and carrying, respectively, the ABCB1 rs9282564 AG and TT genotypes and the COMT rs4680 AA genotype among patients with OA. These findings should be confirmed in independent cohorts, and if a causal relationship between these variants and fatal poisoning in OA is confirmed, then it may be possible at least in theory to personalize prevention of sudden death in this patient group.

  10. Molecular characterization of Echinococcus granulosus cysts in north Indian patients: identification of G1, G3, G5 and G6 genotypes.

    Directory of Open Access Journals (Sweden)

    Monika Sharma

    Full Text Available BACKGROUND: Cystic echinococcosis (CE caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s of the parasite responsible for human hydatidosis in North India. METHODOLOGY/PRINCIPAL FINDINGS: To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1 sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32 were found to be infected with hydatid cyst of either G3 (53.1% or G1 (40.62% genotype and one each of G5 (cattle strain and G6 (camel strain genotype. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate the zoonotic potential of G1 (sheep strain and G3 (buffalo strain genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain in an Asian country and presence of G6 genotype (camel strain in India. The results may have important implications in the planning of control strategies for human hydatidosis.

  11. Molecular characterization of Echinococcus granulosus cysts in north Indian patients: identification of G1, G3, G5 and G6 genotypes.

    Directory of Open Access Journals (Sweden)

    Monika Sharma

    Full Text Available BACKGROUND: Cystic echinococcosis (CE caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s of the parasite responsible for human hydatidosis in North India. METHODOLOGY/PRINCIPAL FINDINGS: To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1 sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32 were found to be infected with hydatid cyst of either G3 (53.1% or G1 (40.62% genotype and one each of G5 (cattle strain and G6 (camel strain genotype. CONCLUSIONS/SIGNIFICANCE: These findings demonstrate the zoonotic potential of G1 (sheep strain and G3 (buffalo strain genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain in an Asian country and presence of G6 genotype (camel strain in India. The results may have important implications in the planning of control strategies for human hydatidosis.

  12. Nitric oxide synthase genotype modulation of impulsivity and ventral striatal activity in adult ADHD patients and healthy comparison subjects.

    Science.gov (United States)

    Hoogman, Martine; Aarts, Esther; Zwiers, Marcel; Slaats-Willemse, Dorine; Naber, Marlies; Onnink, Marten; Cools, Roshan; Kan, Cornelis; Buitelaar, Jan; Franke, Barbara

    2011-10-01

    Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. The NOS1 gene encoding nitric oxide synthase is a candidate gene for ADHD and has been previously linked with impulsivity. In the present study, the authors investigated the effect of a functional variable number of tandem repeats (VNTR) polymorphism in NOS1 (NOS1 exon 1f-VNTR) on the processing of rewards, one of the cognitive deficits in ADHD. A sample of 136 participants, consisting of 87 adult ADHD patients and 49 healthy comparison subjects, completed a reward-related impulsivity task. A total of 104 participants also underwent functional magnetic resonance imaging during a reward anticipation task. The effect of the NOS1 exon 1f-VNTR genotype on reward-related impulsivity and reward-related ventral striatal activity was examined. ADHD patients had higher impulsivity scores and lower ventral striatal activity than healthy comparison subjects. The association between the short allele and increased impulsivity was confirmed. However, independent of disease status, homozygous carriers of the short allele of NOS1, the ADHD risk genotype, demonstrated higher ventral striatal activity than carriers of the other NOS1 VNTR genotypes. The authors suggest that the NOS1 genotype influences impulsivity and its relation with ADHD is mediated through effects on this behavioral trait. Increased ventral striatal activity related to NOS1 may be compensatory for effects in other brain regions.

  13. rs11613352 polymorphism (TT genotype) associates with a decrease of triglycerides and an increase of HDL in familial hypercholesterolemia patients.

    Science.gov (United States)

    Aledo, Rosa; Padró, Teresa; Mata, Pedro; Alonso, Rodrigo; Badimon, Lina

    2015-04-01

    Recent genome-wide association studies have identified a locus on chromosome 12q13.3 associated with plasma levels of triglyceride and high-density lipoprotein cholesterol, with rs11613352 being the lead single nucleotide polymorphism in this genome-wide association study locus. The aim of the study is to investigate the involvement of rs11613352 in a population with high cardiovascular risk due to familial hypercholesterolemia. The single nucleotide polymorphism was genotyped by Taqman(®) assay in a cohort of 601 unrelated familial hypercholesterolemia patients and its association with plasma triglyceride and high-density lipoprotein cholesterol levels was analyzed by multivariate methods based on linear regression. Minimal allele frequency was 0.17 and genotype frequencies were 0.69, 0.27, and 0.04 for CC, CT, and TT genotypes, respectively. The polymorphism is associated in a recessive manner (TT genotype) with a decrease in triglyceride levels (P=.002) and with an increase in high-density lipoprotein cholesterol levels (P=.021) after adjusting by age and sex. The polymorphism rs11613352 may contribute to modulate the cardiovascular risk by modifying plasma lipid levels in familial hypercholesterolemia patients. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Randomized controlled trial of consensus interferon with or without zinc for chronic hepatitis C patients with genotype 2

    Institute of Scientific and Technical Information of China (English)

    Hideyuki Suzuki; Masatomo Mori; Ken Sato; Hitoshi Takagi; Daisuke Kanda; Naondo Sohara; Satoru Kakizaki; Hiroaki Nakajima; Toshiyuki Otsuka; Takeaki Nagamine

    2006-01-01

    AIM: The beneficial effect of zinc supplementation on the efficacy of interferon as a treatment for chronic hepatitis C had been demonstrated in hepatitis virus genotype 1b of high viral load. This study focused on patients with genotype 2, which is more sensitive to interferon than genotype 1b, and used consensus interferon (CIFN) with or without zinc.METHODS: We randomized 83 patients with chronic hepatitis C to CIFN at 18 MIU six times/wk for 4 wk,followed by CIFN at 18 MIU six times/wk for another 20wk, in combination with polaprezinc 300 mg (regimen A,n=41) or as monotherapy (regimen B, n=42). Thirtyone patients in regimen A and 33 patients in regimen B completed the clinical trial; the remaining patients withdrew because of side effects or a transfer to another hospital.RESULTS: Sustained biochemical response, defined as a normal aminotransferase level at the end of the 6-mo post-treatment observation, was 68% and 69%, and sustained virological response, defined as undetectable HCV-RNA at the end of the 6-mo post-treatment observation, was 54% and 67% for regimens A and B,respectively.CONCLUSION: CIFN treatment combined with zinc did not enhance the effect of CIFN as shown by biochemical,virological criteria. No side effects related to polaprezinc were noted.

  15. Genotype-phenotype correlation and functional studies in patients with cystic fibrosis bearing CFTR complex alleles.

    Science.gov (United States)

    Terlizzi, Vito; Castaldo, Giuseppe; Salvatore, Donatello; Lucarelli, Marco; Raia, Valeria; Angioni, Adriano; Carnovale, Vincenzo; Cirilli, Natalia; Casciaro, Rosaria; Colombo, Carla; Di Lullo, Antonella Miriam; Elce, Ausilia; Iacotucci, Paola; Comegna, Marika; Scorza, Manuela; Lucidi, Vincenzina; Perfetti, Anna; Cimino, Roberta; Quattrucci, Serena; Seia, Manuela; Sofia, Valentina Maria; Zarrilli, Federica; Amato, Felice

    2017-04-01

    The effect of complex alleles in cystic fibrosis (CF) is poorly defined for the lack of functional studies. To describe the genotype-phenotype correlation and the results of either in vitro and ex vivo studies performed on nasal epithelial cells (NEC) in a cohort of patients with CF carrying cystic fibrosis transmembrane conductance regulator (CFTR) complex alleles. We studied 70 homozygous, compound heterozygous or heterozygous for CFTR mutations: p.[Arg74Trp;Val201Met;Asp1270Asn], n=8; p.[Ile148Thr;Ile1023_Val1024del], n=5; p.[Arg117Leu;Leu997Phe], n=6; c.[1210-34TG[12];1210-12T[5];2930C>T], n=3; p.[Arg74Trp;Asp1270Asn], n=4; p.Asp1270Asn, n=2; p.Ile148Thr, n=6; p.Leu997Phe, n=36. In 39 patients, we analysed the CFTR gating activity on NEC in comparison with patients with CF (n=8) and carriers (n=4). Finally, we analysed in vitro the p.[Arg74Trp;Val201Met;Asp1270Asn] complex allele. The p.[Ile148Thr;Ile1023_Val1024del] caused severe CF in five compound heterozygous with a class I-II mutation. Their CFTR activity on NEC was comparable with patients with two class I-II mutations (mean 7.3% vs 6.9%). The p.[Arg74Trp;Asp1270Asn] and the p.Asp1270Asn have scarce functional effects, while p.[Arg74Trp;Val201Met;Asp1270Asn] caused mild CF in four of five subjects carrying a class I-II mutation in trans, or CFTR-related disorders (CFTR-RD) in three having in trans a class IV-V mutation. The p.[Arg74Trp;Val201Met;Asp1270Asn] causes significantly (pT] and a class I-II mutation had mild CF or CFTR-RD (gating activity: 18.5-19.0%). The effect of complex alleles partially depends on the mutation in trans. Although larger studies are necessary, the CFTR activity on NEC is a rapid contributory tool to classify patients with CFTR dysfunction. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. The Mutasynthetic Production of CHC-B1 from a Streptomyces avermitilis Mutant in the Presence of Cyclohexanecarboxylic Acid%阿维菌素衍生物CHC-B1的突变生物合成

    Institute of Scientific and Technical Information of China (English)

    姜薇; 汪洋; 张晓琳; 郭伟群; 刘娣

    2009-01-01

    利用成功构建的基因缺失载体pLJ04(pKC1139∶∶△bkdF+△bkdH)对阿维菌素(avennectin)高产菌阿维链霉菌(Streptomyces avermitilis)76-02-e的bkdFGH基因进行缺失,获得的bkdFGH缺失突变株经过摇瓶发酵和HPLC检测,发现该突变株完全丧失了产生阿维菌素的能力.2-甲基丁酸及异丁酸的前体添加试验表明,当有外源前体存在时,突变株又能恢复阿维菌素合成的能力.将该bkdFGH基因缺失突变株命名为S.avermitilis bkd76-3.环己羧酸(CHC)前体添加试验及HPLC检测发现存在4种产物,经LC/MS分析验证,其中两种产物分别为CHC-B1和CHC-A2.

  17. Genetic distance and heterogenecity between quasispecies is a critical predictor to IFN response in Egyptian patients with HCV genotype-4

    Directory of Open Access Journals (Sweden)

    Fouad Inas

    2007-02-01

    Full Text Available Abstract Background HCV is one of the major health problems in Egypt, where it is highly prevalent. Genotype 4 is the most common genotype of HCV and its response to treatment is still a controversy. Methods HCV genotype 4 quasispecies diversity within the 5' untranslated region (5'UTR was studied in a series of 22 native Egyptian patients with chronic hepatitis C virus with no previous treatment who satisfied all NIH criteria for combined treatment of pegylated IFN and ribavirine and was correlated with the outcome of treatment. The study also included 7 control patients with no antiviral treatment. HCV sequencing was done using the TRUGENE HCV 5-NC genotyping kit. Results At the 48th week of treatment, 15 patients (68% showed virological response. Whereas HCV-RNA was still detected in 7 patients (32% in this period; of those, 6 experienced a partial virological response followed by viral breakthrough during treatment. Only one patient did not show any virological or chemical response. The four females included in this study were all responders. There was a significant correlation between the response rate and lower fibrosis (p = 0.026 as well as the total number of mutation spots (including all the insertions, deletions, transitions and transversions (p = 0.007, p = 0.035. Conclusion Patients who responded to interferon treatment had statistically significant less number in both transitions (p = 0.007 and the genetic distances between the quasispecies (p = 0.035. So, viral genetic complexity and variability may play a role in the response to IFN treatment. The consensus alignment of all three groups revealed no characteristic pattern among the three groups. However, the G to A transitions at 160 was observed among non responders who need further study to confirm this observation.

  18. Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

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    Nora Alma Fierro

    2011-12-01

    Full Text Available A high prevalence of occult hepatitis B (OHB genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21 and patients that had recovered from HBV infection (n = 20. Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20 and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta. IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.

  19. Characterization of hepatitis B virus genotypes/subgenotypes in 1301 patients with chronic hepatitis B in North China

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-dong; XU Dong-ping; WANG Lin; LIU Yan; XU Zhi-hui; DAI Jiu-zeng; LI Le; YAO Zeng-tao; XIN Shao-jie; ZHAO Jing-ming

    2011-01-01

    Background There is still a paucity of data on hepati tis B virus (HBV) subgenotype prevalence in North China based on sequencing of large-size samples.In addition,whether HBV genotypes impact drug-resistance-associated and HBV e antigen (HBeAg)-Ioss-associated mutations in patients with chronic hepatitis B (CHB) is still under investigation.This study aimed to disclose clinical prevalence of HBV genotypes/subgenotypes in North China and the clinical implications of HBV genotype classification in respect to HBeAg loss and drug-resistant occurrence.Methods Sera were collected from 1301 nucleos(t)ide analog-experienced CHB patients.Viral DNA was extracted and used as template for HBV genome amplification by nested PCR.DNA sequencing was performed for the analysis of HBV genotypes/subgenotypes,drug-resistance-associated mutations in polymerase gene and HBeAg-loss-associated mutations in precore/basal core promoter (BCP) regions.Results HBV/B,HBV/C,and HBV/D were detected in 190 (14.6%),1096 (84.2%),and 15 (1.2%) patients,respectively.HBV/B2 (182/190),HBV/C2 (1069/1096),and HBV/D1 (12/15) were predominant subgenotypes within individual genotypes.By contrast,C2 prevalence is relatively lower in Beijing area (77.2%) than in other north areas (84.9%-87.4%).HBV/C-infected patients had an older age and a lower serum albumin level but similar HBV DNA and alanine aminotransferase (ALT) levels compared to HBV/B-infected patients.HBV/C infection had a higher incidence of lamivudine-resistant mutations rtM2041/V (44.9% vs.30.2%,P <0.01) and BCP mutations A1762T+G1764A (65.8% vs.40.0%,P<0.01) compared with HBV/B infection.Conclusions C2 is the most prevalent HBV subgenotype followed by B2 in CHB patients in North China; and HBV genotype prevalence is influenced by immigrant population.HBV/C infection is likely to have longer disease duration and severer liver functional impairment and might be more susceptible to develop lamivudine resistance compared to

  20. High Diversity of vacA and cagA Helicobacter pylori Genotypes in Patients with and without Gastric Cancer

    Science.gov (United States)

    López-Vidal, Yolanda; Ponce-de-León, Sergio; Castillo-Rojas, Gonzalo; Barreto-Zúñiga, Rafael; Torre-Delgadillo, Aldo

    2008-01-01

    Background Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. Methodology/Principal Findings Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008), and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003). A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036). A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003). Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. Conclusion/Significance High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work. PMID:19050763

  1. High diversity of vacA and cagA Helicobacter pylori genotypes in patients with and without gastric cancer.

    Directory of Open Access Journals (Sweden)

    Yolanda López-Vidal

    Full Text Available BACKGROUND: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008, and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003. A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036. A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003. Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. CONCLUSION/SIGNIFICANCE: High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work.

  2. Safety and efficacy of simeprevir plus sofosbuvir with or without ribavirin in patients with decompensated genotype 1 hepatitis C cirrhosis.

    Science.gov (United States)

    Modi, Apurva A; Nazario, Hector; Trotter, James F; Gautam, Manjushree; Weinstein, Jeffrey; Mantry, Parvez; Barnes, Maisha; Habib, Adil; McAfee, Jean; Teachenor, Olga; Tujague, Lauren; Gonzalez, Stevan

    2016-03-01

    Combination antiviral therapy involving sofosbuvir (SOF) and simeprevir (SIM) is a treatment option in patients with genotype 1 chronic hepatitis C; however, the safety of this regimen in patients with decompensated cirrhosis is not established. Data from a combined treatment cohort of 2 large hepatology referral centers were evaluated to assess for safety and efficacy of SIM plus SOF with or without ribavirin (RBV) in patients with Child B or C cirrhosis. All (n = 42) patients included in the analysis had Child B (n = 35) or C (n = 7) cirrhosis and received 400 mg daily of SOF plus 150 mg daily of SIM, with (n = 7) or without (n = 35) RBV, for 12 weeks. Of the 42 patients in this cohort, 31 (74%) were male, 22 (52%) had failed prior treatments, and 28 (67%) were genotype 1a. Prior decompensating events included encephalopathy (57%), fluid overload (88%), or variceal hemorrhage (24%). Median Model for End-Stage Liver Disease score was 12 (range, 6-25). Treatment was well tolerated overall with more than one-half (57%) reporting no adverse events. In those reporting adverse events, the most common were fatigue (n = 6), insomnia (n = 4), headache (n = 5), nausea (n = 4), and grade 1 rash (n = 1). One patient developed chemical pancreatitis that did not require treatment discontinuation. Three of 7 patients who received RBV developed anemia, with 2 requiring blood transfusions and 1 requiring a dose reduction. No episodes of decompensation requiring hospitalization or deaths occurred on treatment. Of 42 patients, 38 (90%) patients had negative viral load at end of treatment (EOT), and 31 of 42 patients (74%) achieved sustained virological response 12 weeks after EOT; 10 of 10 patients (100%) with HCV genotype 1b achieved sustained virological response for 12 weeks (SVR12). In conclusion, SOF plus SIM was very well tolerated in patients with advanced Child B/C decompensated cirrhosis. Overall, 74% of patients achieved SVR12

  3. Prognostic phenotypic and genotypic factors associated with photodynamic therapy response in patients with age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tsuchihashi T

    2014-12-01

    Full Text Available Takashi Tsuchihashi,1 Keisuke Mori,1 Kuniko Horie-Inoue,2 Yasushi Okazaki,3 Takuya Awata,4,5 Satoshi Inoue,2 Shin Yoneya1 1Department of Ophthalmology, 2Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Division of Translational Research, Research Center for Genomic Medicine, 4Division of Endocrinology and Diabetes, Department of Medicine, 5Division of RI Laboratory, Biomedical Research Center, Saitama Medical University, Iruma, Saitama, Japan Background: This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT for age-related macular degeneration (AMD.Methods: The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996 in the complement factor H (CFH gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1 gene, two SNPs (rs699947, rs2010963 in the vascular endothelial growth factor (VEGF gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287 in the pigment epithelium-derived factor (PEDF gene were evaluated. Results: A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10-4, 1.95×10-2, 1.24×10-3, respectively. Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10-3. Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10-3; odds ratio 2.363; 95% confidence interval 1.303–4.285.Conclusion: The HTRA1

  4. Human papillomavirus genotyping by multiplex pyrosequencing in cervical cancer patients from India

    Indian Academy of Sciences (India)

    Cheryl M Travasso; Mona Anand Mansi; Mansi Samarth; Aditi Deshpande; Chandan Kumar-Sinha

    2008-03-01

    Cervical cancer is a leading cause of cancer-related deaths among women in India. Human papillomavirus (HPV) infection is the causative agent of cervical cancer; and infection with the high-risk genotypes, predominantly HPV16 and 18, is the biggest risk factor. Vaccines targeting HPV16 and 18 have been found to confer protection in large-scale clinical trials. HPV genotyping has traditionally been carried out to screen the population “at risk” using indirect methods based on polymerase chain reaction (PCR) using consensus primers combined with various DNA hybridization techniques, and often followed by the sequencing of candidate products. Recently, a high-throughput and direct method based on DNA sequencing has been described for HPV genotyping using multiplex pyrosequencing. We present a pilot study on HPV genotyping of cervical cancer and non-malignant cervical samples using multiplex pyrosequencing. Using genomic DNA from cell lines, cervical biopsies, surgical tissues or formalin-fixed, paraffin-embedded tissue samples, we could successfully resolve 6 different HPV types out of the 7 tested, with their prevalence found to be in agreement with earlier reports. We also resolved coinfections with two different HPV types in several samples. An HPV16 genotype with a specific and recurrent sequence variation was observed in 8 cancer samples and one non-malignant sample. We find this technique eminently suited for high-throughput applications, which can be easily extended to large sample cohorts to determine a robust benchmark for HPV genotypes prevalent in India.

  5. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection.

    Science.gov (United States)

    Osinusi, Anu; Townsend, Kerry; Kohli, Anita; Nelson, Amy; Seamon, Cassie; Meissner, Eric G; Bon, Dimitra; Silk, Rachel; Gross, Chloe; Price, Angie; Sajadi, Mohammad; Sidharthan, Sreetha; Sims, Zayani; Herrmann, Eva; Hogan, John; Teferi, Gebeyehu; Talwani, Rohit; Proschan, Michael; Jenkins, Veronica; Kleiner, David E; Wood, Brad J; Subramanian, G Mani; Pang, Phillip S; McHutchison, John G; Polis, Michael A; Fauci, Anthony S; Masur, Henry; Kottilil, Shyam

    There is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV). To evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir. Open-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed. Fifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily for 12 weeks. The primary study outcome was the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment. Forty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug. In this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype

  6. Filaggrin genotype determines functional and molecular alterations in skin of patients with atopic dermatitis and ichthyosis vulgaris.

    Directory of Open Access Journals (Sweden)

    Mårten C G Winge

    Full Text Available BACKGROUND: Several common genetic and environmental disease mechanisms are important for the pathophysiology behind atopic dermatitis (AD. Filaggrin (FLG loss-of-function is of great significance for barrier impairment in AD and ichthyosis vulgaris (IV, which is commonly associated with AD. The molecular background is, however, complex and various clusters of genes are altered, including inflammatory and epidermal-differentiation genes. OBJECTIVE: The objective was to study whether the functional and molecular alterations in AD and IV skin depend directly on FLG loss-of-function, and whether FLG genotype determines the type of downstream molecular pathway affected. METHODS AND FINDINGS: Patients with AD/IV (n = 43 and controls (n = 15 were recruited from two Swedish outpatient clinics and a Swedish AD family material with known FLG genotype. They were clinically examined and their medical history recorded using a standardized questionnaire. Blood samples and punch biopsies were taken and trans-epidermal water loss (TEWL and skin pH was assessed with standard techniques. In addition to FLG genotyping, the STS gene was analyzed to exclude X-linked recessive ichthyosis (XLI. Microarrays and quantitative real-time PCR were used to compare differences in gene expression depending on FLG genotype. Several different signalling pathways were altered depending on FLG genotype in patients suffering from AD or AD/IV. Disease severity, TEWL and pH follow FLG deficiency in the skin; and the number of altered genes and pathways are correlated to FLG mRNA expression. CONCLUSIONS: We emphasize further the role of FLG in skin-barrier integrity and the complex compensatory activation of signalling pathways. This involves inflammation, epidermal differentiation, lipid metabolism, cell signalling and adhesion in response to FLG-dependent skin-barrier dysfunction.

  7. Genotype-phenotype correlation in cystic fibrosis patients bearing [H939R;H949L] allele

    Directory of Open Access Journals (Sweden)

    Angela Polizzi

    2011-01-01

    Full Text Available Cystic fibrosis (CF is caused by CFTR (cystic fibrosis transmembrane conductance regulator gene mutations. We ascertained five patients with a novel complex CFTR allele, with two mutations, H939R and H949L, inherited in cis in the same exon of CFTR gene, and one different mutation per patient inherited in trans in a wide population of 289 Caucasian CF subjects from South Italy. The genotype-phenotype relationship in patients bearing this complex allele was investigated. The two associated mutations were related to classical severe CF phenotypes.

  8. Increased level of acute phase reactants in patients infected with modern Mycobacterium tuberculosis genotypes in Mwanza, Tanzania

    DEFF Research Database (Denmark)

    Stavrum, Ruth; PrayGod, George; Range, Nyagosya;

    2014-01-01

    BACKGROUND: There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from...... a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different lineages. METHODS: Two-hundred-fifty-two isolates from pulmonary TB patients in Mwanza, Tanzania were...... characterized by spoligotyping, and 45 isolates were further characterized by mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). The patients' level of the acute phase reactants AGP, CRP and neutrophil counts, in addition to BMI, were measured and compared to the M...

  9. Hepatitis B virus prevalence, risk factors and genotype distribution in HIV infected patients from West Java, Indonesia.

    Science.gov (United States)

    Fibriani, Azzania; Wisaksana, Rudi; Alisjahbana, Bachti; Indrati, Agnes; Schutten, Martin; van Crevel, Reinout; van der Ven, Andre; Boucher, Charles A B

    2014-04-01

    Indonesia currently faces both an increasing HIV incidence and a high hepatitis B virus (HBV) burden. The objective of our study is to examine the prevalence, risk factors, and genotypic distribution of HBV infection among HIV infected patients in West Java, Indonesia. A cross sectional study was conducted among a cohort of HIV infected patients in 2008. Demographic and disease related variables were compared between HBV negative and positive patients. Logistic regression was applied to determine risk factors for HBV co-infection. HBV and HIV genotyping was performed in co-infected patients. Of 636 HIV-infected patients, the rate of HBV co-infection was 7%. The proportion of males was higher in HBV/HIV co-infected patients than in HIV mono-infected patients (93% vs. 72%, P=0.001). A history of injecting drug use (IDU), but not tattooing, was associated with HBV co-infection [P=0.035 OR 2.41 (95% CI 1.06-5.47)]. In the HIV and HBV treatment naive patients, CD4 cells counts Java. However, an increased prevalence was observed in men with a history of IDU, underlining the need for routine HBV screening and monitoring. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Genotyping of Haemophilus influenzae type b strains and their incidence in the clinical samples isolated from Iranian patients

    Science.gov (United States)

    Bagherzadeh Khodashahri, Somayeh; Siadat, Seyed Davar; Rahbar, Mohammad; Abdollahpour-Alitappeh, Meghdad; Vaziri, Farzam; Rahnamaye-Farzami, Mrjan; Mohammadzadeh, Mona; Davari, Mehdi; Fateh, Abolfazl; Masoumi, Morteza

    2015-01-01

    Background and Objective: Haemophilus influenzae type b (Hib) is divided into two distinct genotypes, type I and type II, based on the structure of capsular polysaccharides. The capsulation locus of Haemophilus influenzae type b consists of three functionally distinct regions, designated regions 1 to 3. Region III contains hcsA and hcsB genes; however, notable sequence variation in this region can be used to recognize different Hib genotypes. The purpose of this study was to investigate the prevalence and genotype of the Hib strains isolated from patients with invasive disease in Iran. Materials and Methods: In the present study, 8 pairs of primers were used for identification and serotyping of encapsulated Haemophilus influenzae strains, as well as confirmation of species identification. Additionally, in order to identify the capsular genotypes of Haemophilus influenzae type b (type I and II), two additional primer pairs were used to amplify the hcsA gene. Results: Out of 50 isolates of H. influenzae, four were found to be type b. Interestingly, among these 4 Hib isolates, 2 strains belonged to the type-II category. Conclusion: Our study shows that the prevalence of both Hib types I and II seems to be high in Iran. PMID:26668700

  11. Pseudomonas aeruginosa blood stream infection isolates from patients with recurrent blood stream infection: Is it the same genotype?

    Science.gov (United States)

    McCARTHY, K L; Kidd, T J; Paterson, D L

    2017-08-22

    The type identity of strains of Pseudomonas aeruginosa from primary and recurrent blood stream infection (BSI) has not been widely studied. Twenty-eight patients were identified retrospectively from 2008 to 2013 from five different laboratories; available epidemiological, clinical and microbiological data were obtained for each patient. Isolates were genotyped by iPLEX MassARRAY MALDI-TOF MS and rep-PCR. This showed that recurrent P. aeruginosa BSI was more commonly due to the same genotypically related strain as that from the primary episode. Relapse due to a genotypically related strain occurred earlier in time than a relapsing infection from an unrelated strain (median time: 26 vs. 91 days, respectively). Line related infections were the most common source of suspected BSI and almost half of all BSI episodes were associated with neutropenia, possibly indicating translocation of the organism from the patient's gut in this setting. Development of meropenem resistance occurred in two relapse isolates, which may suggest that prior antibiotic therapy for the primary BSI was a driver for the subsequent development of resistance in the recurrent isolate.

  12. [Prevalence and genotype distribution changes in hepatitis C virus co-infection among human immunodeficiency virus-infected patients].

    Science.gov (United States)

    Cifuentes, Celia; Mancebo-Hernández, María; Pérez-Navarro, Elisabet; Recio, Eva; Monje-Agudo, Patricia; Valiente, Adoración; Pineda, Juan A

    2015-02-01

    The prevalence of hepatitisC is decreasing among new diagnoses of HIV/HCV coinfection in Spain. The increasing use of the HCV treatment could have changed the HCV genotype distribution. The aim of this study is to analyze changes in the prevalence of HCV coinfection and in HCV genotype distribution among HIV-infected patients. A serial cross-sectional study was conducted that included all HIV-infected patients who attended the Outpatient Clinic of a hospital in Andalusia, between September 2008 and February 2009 (first period), and between January 2013 and June 2013 (second period). A total of 520 and 651 patients were included in the first and second period, respectively. The risk factors of HCV infection in the first vs. second period were: IDU, 319 (61%) vs. 348 (53%); heterosexual contact, 111 (21%) vs. 135 (21%); homosexual men, 76 (15%) vs. 114 (22%) (P=.006). The prevalence of HCV antibody per period was: 358 (69%) vs. 380 (58%) (P=virus and active infection during the last 5 years. However, the HCV genotype distribution has not changed. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  13. Human cytomegalovirus glycoprotein B genotypes in blood of AIDS patients: lack of association with either the viral DNA load in leukocytes or presence of retinitis.

    Science.gov (United States)

    Gilbert, C; Handfield, J; Toma, E; Lalonde, R; Bergeron, M G; Boivin, G

    1999-09-01

    It has been suggested that human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes could be used as a marker for viral virulence in patients with AIDS. The present study was designed to evaluate a possible association between specific gB genotypes, the presence of HCMV retinitis, and the HCMV viral load. Fifty-four blood samples were obtained from 54 HIV- and HCMV-infected patients. Twenty-seven of these patients were asymptomatic for HCMV, whereas the other 27 patients had been diagnosed recently with HCMV retinitis. HCMV gB genotyping was carried out by using restriction enzyme analysis of PCR-amplified PMNL extracts. Determination of the HCMV viral load in the same specimens was carried out using a quantitative-PCR. HCMV gB genotype 2 was found more frequently than other genotypes in PCR-amplified polymorphonuclear leukocytes (PMNL) of patients with AIDS (P < 0.05) but not more frequently in samples from patients with HCMV retinitis. No significant association was found between any HCMV gB genotypes and the viral load in blood. In conclusion, the actual HCMV gB genotyping system using PMNL provides no additional benefit over the viral load in blood for identification of HIV-infected subjects at risk of HCMV disease.

  14. Genotype- phenotype correlation in trisomy X: a retrospective study of a selected group of 36 patients and review of literature.

    Science.gov (United States)

    Butnariu, Lăcrămioara; Rusu, Cristina; Caba, Lavinia; Pânzaru, Monica; Braha, Elena; Grămescu, Mihaela; Popescu, Roxana; Bujoranu, C; Gorduza, E V

    2013-01-01

    Trisomy X (47,XXX) is a gonosomal aneuploidy characterized by the presence of an extra X chromosome in a female person. Usually the diagnosis is established made postnatally by chromosome analysis in patients with suggestive clinical signs. Clinical signs vary by age. In prepubertal patients have a growth retardation associated with uncharacteristic facial dysmorphism, mild mental retardation with behavioral disorders, plus clinical signs of ovarian dysgenesis, postpubertal. We analyzed retrospectively the genotype - phenotype correlations for a selected group of 36 patients diagnosed with trisomy X (homogeneous or mosaic) by cytogenetic methods (X chromatin and karyotype). Analysis of the clinical data of 36 patients diagnosed with trisomy X and correlation with the results of X chromatin and karyotype. Clinical signs detected in patients with homogeneous trisomy X 47,XXX (22.22%), mosaic 46,XX/47,XXX (16.66%) or 47,XXX/48,XXXX (5.55%) were prepubertal, growth retardation associated with dysmorphic facial (upslanted palpebral fissure, epichantus, thin lips) and postpubertal, signs of ovarian dysgenesis (secondary amenorrhea, early menopause). The phenotype of patients with different gonosomal mosaic corresponding to Turner syndrome, incorporating a cell line with trisomy X (55.55%) was variable, correlated with the type of chromosomal abnormalities detected. The results of our study are similar to those obtained in other studies and emphasizes that phenotypic variability of patients with trisomy X feature makes it difficult to genotype - phenotype correlations.

  15. May some HCV genotype 1 patients still benefit from dual therapy? The role of very early HCV kinetics.

    Science.gov (United States)

    Tontodonati, Monica; Cento, Valeria; Polilli, Ennio; Colabattista, Cecilia; Cascella, Raffaella; Sciotti, Mariapina; Di Giammartino, Dante; Trave, Francesca; Di Maio, Velia Chiara; Monarca, Roberto; Di Candilo, Francesco; Prinapori, Roberta; Rastrelli, Elena; Vecchiet, Jacopo; Ceccherini-Silberstein, Francesca; Manzoli, Lamberto; Giardina, Emiliano; Perno, Carlo Federico; Parruti, Giustino

    2015-10-01

    When treating HCV patients with conventional dual therapy in the current context of rapidly evolving HCV therapy, outcome prediction is crucial and HCV kinetics, as early as 48 hours after the start of treatment, may play a major role. We aimed at clarifying the role of HCV very early kinetics. We consecutively enrolled mono-infected HCV patients at 7 treatment sites in Central Italy and evaluated the predictive value of logarithmic decay of HCV RNA 48 hours after the start of dual therapy (Delta48). Among the 171 enrolled patients, 144 were evaluable for early and sustained virological response (EVR, SVR) prediction; 108 (75.0%) reached EVR and 84 (58.3%) reached SVR. Mean Delta 48 was 1.68 ± 1.22 log10 IU/ml, being higher in patients with SVR and EVR. Those genotype-1 patients experiencing a Delta 48 >2 logs showed a very high chance of success (100% positive predictive value), even in the absence of rapid virological response (RVR). Evaluation of very early HCV kinetics helped identify a small but significant proportion of genotype-1 patients (close to 10%) in addition to those identified with RVR, who could be treated with dual therapy in spite of not reaching RVR. In the current European context, whereby sustainability of HCV therapy is a crucial issue, conventional dual therapy may still play a reasonable role in patients with good tolerance and early prediction of success.

  16. The Clinical and Economic Impact of Genotype Testing at First-line Antiretroviral Therapy Failure for HIV-Infected Patients in South Africa

    Science.gov (United States)

    Levison, Julie H.; Wood, Robin; Scott, Callie A.; Ciaranello, Andrea L.; Martinson, Neil A.; Rusu, Corina; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2013-01-01

    Background. In resource-limited settings, genotype testing at virologic failure on first-line antiretroviral therapy (ART) may identify patients with wild-type (WT) virus. After adherence counseling, these patients may safely and effectively continue first-line ART, thereby delaying more expensive second-line ART. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications International model of human immunodeficiency virus (HIV) disease to simulate a South African cohort of HIV-infected adults at first-line ART failure. Two strategies were examined: no genotype vs genotype, assuming availability of protease inhibitor–based second-line ART. Model inputs at first-line ART failure were mean age 38 years, mean CD4 173/µL, and WT virus prevalence 20%; genotype cost was $300 per test and delay to results, 3 months. Outcomes included life expectancy, per-person costs (2010 US dollars), and incremental cost-effectiveness ratios (dollars per years of life saved [YLS]). Results. No genotype had a projected life expectancy of 106.1 months, which with genotype increased to 108.3 months. Per-person discounted lifetime costs were $16 360 and $16 540, respectively. Compared to no genotype, genotype was very cost-effective, by international guidance, at $900/YLS. The cost-effectiveness of genotype was sensitive to prevalence of WT virus (very cost-effective when prevalence ≥12%), CD4 at first-line ART failure, and ART efficacy. Genotype-associated delays in care ≥5 months decreased survival and made no genotype the preferred strategy. When the test cost was ART failure is very cost-effective in South Africa. The cost-effectiveness of this strategy will depend on prevalence of WT virus and timely response to genotype results. PMID:23087386

  17. Human leukocyte antigen genotypes and trial of desensitization in patients with oxcarbazepine-induced skin rash: a pilot study.

    Science.gov (United States)

    Lee, Bolyun; Yu, Hee Joon; Kang, Eun-Suk; Lee, Munhyang; Lee, Jeehun

    2014-08-01

    Skin rash associated with specific antiepileptic drugs occurs not infrequently and it usually necessitates discontinuation of the causative drugs. An alternative strategy is to desensitize the individual to the offending drug. We checked the human leukocyte antigen genotypes and conducted a pilot study to investigate the usefulness and safety of desensitization in pediatric patients with skin rash associated with oxcarbazepine. We enrolled 19 patients with epilepsy who had discontinued oxcarbazepine because of skin rash despite an initial good response and then became refractory to other antiepileptic drugs along with an individual with paroxysmal kinesigenic dyskinesia with a similar situation. High-resolution HLA-A and -B genotyping was performed to investigate the genetic risk. The desensitization began with 0.1 mg daily reaching 120 mg on the thirty-first day. Thereafter, the dose was increased at a rate of 12 mg/day. Nineteen patients completed the desensitization protocol to a target dosage over 2-5 months. Five patients developed itching and erythema during desensitization, but the symptoms disappeared after withholding a dose increment transiently. There were no human leukocyte antigen genotypes relevant to aromatic antiepileptic drug-induced severe hypersensitivity reactions. The seizure frequency was reduced to less than at baseline in 18 individuals. This study demonstrated 95% efficacy, including 42% seizure-free patients and the favorable tolerability of desensitization to oxcarbazepine in patients with intractable epilepsy and one patient with paroxysmal kinesigenic dyskinesia. Screening for sensitive human leukocyte antigen types and exclusion of severe hypersensitivity reactions should precede desensitization. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Hospitalization due to norovirus and genotypes of rotavirus in pediatric patients, state of Espírito Santo

    Directory of Open Access Journals (Sweden)

    Leandro Rua Ribeiro

    2008-03-01

    Full Text Available Viruses are the leading cause for hospitalization due to gastroenteritis worldwide. Group A rotaviruses (RV are the most prevalent and are assorted in glycoproteins (G and protease sensitive (P dual genotypes based on polymorphic genes that encode the external VP7 and VP4 capsid proteins, respectively. Noroviruses (NoV have increasingly answered by sporadic gastroenteritis. This study aimed to determine the prevalence of NoV and RV in 68 hospitalized children, between July 2004 and November 2006, at a pediatric hospital in Vitória city, state of Espírito Santo, Southeastern Brazil. Nucleic acid was extracted from fecal suspension following the guanidine-silica procedure. Reverse transcriptase-polymerase chain reaction (RT-PCR and polyacrylamide gel electrophoresis were employed for NoV and RV detection, respectively. RV genotyping was accomplished using RT-PCR followed by heminested multiplex PCR with specific primers for the most prevalent types of G and P. Fecal samples were positive for NoV and RV in 39.7% (27/68 and 20.5% (14/68, respectively and together were responsible for 60% (41/68 of the cases. RV genotypes were: 50% G9P[8], 28.7% G2P[4], 7.1% G1P[8], G2P[8] and G?P[8]. Vomit was a prominent manifestation observed in 92% and 85% of the NoV and RV cases, respectively. The median hospitalization was 5 and 5.5 days for the patients infected with NoV and RV, respectively. The data showed that NoV prevailed over RV and it also corroborated the emergence of RV G9 genotype followed by G2P[4], reinforcing the need for RV genotype surveillance.

  19. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, Louise B; Kronborg, Gitte

    2007-01-01

    in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk...... with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic...... HIV Cohort Study (DHCS). METHODS: We included all patients in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We...

  20. HLA-G 14-bp Ins/Ins Genotype in Patients Harbouring Helicobacter pylori Infection: A Potential Risk Factor?

    Science.gov (United States)

    Genre, J; Reginaldo, F P Santos; Andrade, J Marco de Leon; Lima, F P; da Camara, A V Coutinho; Donadi, E A; Crispim, J C

    2016-01-01

    H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA-G), a non-classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA-G 14-bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA-G and its genetic polymorphisms in bacterial infection. Sixty-eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA-G 14-bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14-bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection.

  1. Colonic mucosal gene expression and genotype in irritable bowel syndrome patients with normal or elevated fecal bile acid excretion.

    Science.gov (United States)

    Camilleri, Michael; Carlson, Paula; Acosta, Andres; Busciglio, Irene

    2015-07-01

    The mucosal gene expression in rectosigmoid mucosa (RSM) in irritable bowel syndrome with diarrhea (IBS-D) is unknown. Our objectives were, first, to study mRNA expression [by RT(2) PCR of 19 genes pertaining to tight junctions, immune activation, intestinal ion transport and bile acid (BA) homeostasis] in RSM in IBS-D patients (n = 47) and healthy controls (n = 17) and study expression of a selected protein (PDZD3) in 10 IBS-D patients and 4 healthy controls; second, to assess RSM mRNA expression according to genotype and fecal BA excretion (high ≥ 2,337 μmol/48 h); and third, to determine whether genotype or mucosal mRNA expression is associated with colonic transit or BA parameters. Fold changes were corrected for false detection rate for 19 genes studied (P colonic transit. We concluded that mucosal ion transport mRNA (for several genes and PDZD3 protein) is upregulated and barrier protein mRNA downregulated in IBS-D compared with healthy controls, independent of genotype. There are no differences in gene expression in IBS-D with high compared with normal fecal BA excretion.

  2. Sofosbuvir with peginterferon-ribavirin for 12 weeks in previously treated patients with hepatitis C genotype 2 or 3 and cirrhosis

    Science.gov (United States)

    Lawitz, Eric; Poordad, Fred; Brainard, Diana M; Hyland, Robert H; An, Di; Dvory-Sobol, Hadas; Symonds, William T; McHutchison, John G; Membreno, Fernando E

    2015-01-01

    Sofosbuvir (SOF) in combination with ribavirin (RBV) for 12 or 24 weeks is the current standard of care for patients infected with hepatitis C virus (HCV) genotypes 2 and 3, respectively. However, in clinical trials treatment-experienced patients, particularly those with cirrhosis, had suboptimal sustained virological response (SVR) rates. We assessed the efficacy and safety of sofosbuvir plus peginterferon and ribavirin (SOF+Peg-IFN+RBV) administered for 12 weeks to treatment-experienced patients with HCV genotypes 2 and 3, with and without cirrhosis. We enrolled 47 patients in this open-label, nonrandomized, uncontrolled phase 2 study. The primary endpoint was the proportion of patients with SVR at 12 weeks after cessation of study treatment (SVR12). The overall rate of SVR12 was 89% (95% confidence interval [CI]: 77-97). Rates of SVR12 were higher in patients with genotype 2 than in those with genotype 3, 96% (95% CI: 78-100) and 83% (95% CI: 62-95), respectively. Rates of SVR12 were similar in patients with and without cirrhosis: for genotype 2, 93% of patients with cirrhosis and 100% of patients without cirrhosis achieved SVR12, and for genotype 3, the SVR12 rate was 83% in patients both with and without cirrhosis. One patient discontinued study treatment because of an adverse event and four patients experienced serious adverse events. The most common adverse events were influenza-like illness, fatigue, anemia, and neutropenia. Conclusion: In treatment-experienced patients with HCV genotypes 2 and 3, 12-week administration of SOF+Peg-IFN+RBV provided high SVR rates, irrespective of cirrhosis status. No safety concerns were identified. (Hepatology 2015;61:769–775) PMID:25322962

  3. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, Louise B; Kronborg, Gitte

    2007-01-01

    in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk...... with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic...

  4. Test of IL28B polymorphisms in chronic hepatitis C patients treated with PegIFN and ribavirin depends on HCV genotypes: results from a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhifang Jia

    Full Text Available BACKGROUND: Many studies have been published on the association between single nucleotide polymorphisms (SNP near the IL28B gene and response to the combined treatments of pegylated-interferon (PegIFN and ribavirin (RBV in chronic HCV-infected patients, but without identical conclusions. The aim of this study was to assess impact of the IL28B polymorphisms on the effect of HCV standard treatment using meta-analysis based method. METHODS: Association studies between polymorphisms of rs12979860 or rs8099917 and response to PegIFN/RBV treatment in chronic HCV patients were retrieved from PubMed. Data of qualified studies on sustained virological response (SVR in different genotypes were extracted and analyzed using meta-analysis method in Stata 10 software. RESULTS: Thirty-four papers, containing 46 independent studies, were included in the analysis. In the HCV G1/4 patients without treatment history, individuals carrying rs12979860 CC genotype were more likely to achieve SVR (OR 3.97, 95%CI 3.29-4.80 compared to those carrying CT/TT genotypes. Similar results were observed in the HCV G1/4 patients with unsuccessful or unknown treatment history (OR 3.76, 95%CI 2.67-5.28 or in the patients co-infected with human immunodeficiency virus (OR 5.20, 95%CI 3.04-8.90. However, associations could not be observed in HCV G2/3 patients. For rs8099917, similar results were obtained for genotype TT compared to genotypes TG/GG, indicating that TT genotype was significantly associated with better treatment response in patients infected with genotype 1 or 4 HCV, but not genotype 2 or 3 HCV. CONCLUSION: Polymorphisms of rs12979860 and rs8099917 near IL28B only associate with the treatment response to PegIFN/RBV in patients infected with HCV genotype 1 or 4 but not with genotype 2 or 3, irrespective of the previous treatment history or HIV co-infected status. Therefore, identification of IL28B genotypes is necessary only in patients infected with relatively difficult

  5. Genotyping of Mycobacterium leprae present on Ziehl-Neelsen-stained microscopic slides and in skin biopsy samples from leprosy patients in different geographic regions of Brazil.

    Science.gov (United States)

    Fontes, Amanda Nogueira Brum; Gomes, Harrison Magdinier; Araujo, Marcelo Ivens de; Albuquerque, Edson Cláudio Araripe de; Baptista, Ida Maria Foschiani Dias; Moura, Maria Manuela da Fonseca; Rezende, Denise Silva; Pessolani, Maria Cristina Vidal; Lara, Flávio Alves; Pontes, Maria Araci de Andrade; Gonçalves, Heitor de Sá; Lucena-Silva, Norma; Sarno, Euzenir Nunes; Vissa, Varalakshmi D; Brennan, Patrick J; Suffys, Philip Noel

    2012-12-01

    We analysed 16 variable number tandem repeats (VNTR) and three single-nucleotide polymorphisms (SNP) in Mycobacterium leprae present on 115 Ziehl-Neelsen (Z-N)-stained slides and in 51 skin biopsy samples derived from leprosy patients from Ceará (n = 23), Pernambuco (n = 41), Rio de Janeiro (n = 22) and Rondônia (RO) (n = 78). All skin biopsies yielded SNP-based genotypes, while 48 of the samples (94.1%) yielded complete VNTR genotypes. We evaluated two procedures for extracting M. leprae DNA from Z-N-stained slides: the first including Chelex and the other combining proteinase and sodium dodecyl sulfate. Of the 76 samples processed using the first procedure, 30.2% were positive for 16 or 15 VNTRs, whereas of the 39 samples processed using the second procedure, 28.2% yielded genotypes defined by at least 10 VNTRs. Combined VNTR and SNP analysis revealed large variability in genotypes, but a high prevalence of SNP genotype 4 in the Northeast Region of Brazil. Our observation of two samples from RO with an identical genotype and seven groups with similar genotypes, including four derived from residents of the same state or region, suggest a tendency to form groups according to the origin of the isolates. This study demonstrates the existence of geographically related M. leprae genotypes and that Z-N-stained slides are an alternative source for M. leprae genotyping.

  6. Genotyping of Mycobacterium leprae present on Ziehl-Neelsen-stained microscopic slides and in skin biopsy samples from leprosy patients in different geographic regions of Brazil

    Directory of Open Access Journals (Sweden)

    Amanda Nogueira Brum Fontes

    2012-12-01

    Full Text Available We analysed 16 variable number tandem repeats (VNTR and three single-nucleotide polymorphisms (SNP in Mycobacterium leprae present on 115 Ziehl-Neelsen (Z-N-stained slides and in 51 skin biopsy samples derived from leprosy patients from Ceará (n = 23, Pernambuco (n = 41, Rio de Janeiro (n = 22 and Rondônia (RO (n = 78. All skin biopsies yielded SNP-based genotypes, while 48 of the samples (94.1% yielded complete VNTR genotypes. We evaluated two procedures for extracting M. leprae DNA from Z-N-stained slides: the first including Chelex and the other combining proteinase and sodium dodecyl sulfate. Of the 76 samples processed using the first procedure, 30.2% were positive for 16 or 15 VNTRs, whereas of the 39 samples processed using the second procedure, 28.2% yielded genotypes defined by at least 10 VNTRs. Combined VNTR and SNP analysis revealed large variability in genotypes, but a high prevalence of SNP genotype 4 in the Northeast Region of Brazil. Our observation of two samples from RO with an identical genotype and seven groups with similar genotypes, including four derived from residents of the same state or region, suggest a tendency to form groups according to the origin of the isolates. This study demonstrates the existence of geographically related M. leprae genotypes and that Z-N-stained slides are an alternative source for M. leprae genotyping.

  7. Subgrouping of patients with oral lichen planus according to cytochrome P450 enzyme phenotype and genotype

    DEFF Research Database (Denmark)

    Kragelund, Camilla; Jensen, Siri Beier; Hansen, Claus

    2014-01-01

    Objective. This study aimed to determine if the activity of the environmentally influenced cytochrome P450 enzyme CYP1A2, alone or in combination with CYP2D6*4 genotype, discriminates subgroups of oral lichen planus (OLP) according to lifestyle factors and clinical manifestations. Study Design. A...

  8. Comparative genotyping of Campylobacter jejuni strains from patients with Guillain-Barré syndrome

    NARCIS (Netherlands)

    Z. Islam (Zhahirul); A.F. van Belkum (Alex); J.A. Wagenaar (Jaap); A.J. Cody (Alison); A.G. de Boer (Albert); H. Tabor (Helen); B.C. Jacobs (Bart); K.A. Talukder (Kaisar); H.P. Endtz (Hubert)

    2009-01-01

    textabstractBackground: Campylobacter jejuni is a common cause of acute gastroenteritis and is associated with post-infectious neuropathies such as the Guillain-Barré syndrome (GBS) and the Miller Fisher syndrome (MFS). We here present comparative genotyping of 49 C. jejuni strains from Bangladesh t

  9. HFE mutations and hemochromatosis in Danish patients admitted for HFE genotyping

    DEFF Research Database (Denmark)

    Koefoed, P; Dalhoff, K; Dissing, J

    2002-01-01

    .0% (0%) C282Y homozygotes, 5.8% (2.6%) H63D/C282Y compound heterozygotes and 1.9% (3.1%) S65C heterozygotes. The values for 420 Danish blood donors are shown in parentheses. The distribution of genotypes in group B was similar to that of the blood donors. Serum ferritin, transferrin iron saturation...

  10. Comparative genotyping of Campylobacter jejuni strains from patients with Guillain-Barré syndrome

    NARCIS (Netherlands)

    Z. Islam (Zhahirul); A.F. van Belkum (Alex); J.A. Wagenaar (Jaap); A.J. Cody (Alison); A.G. de Boer (Albert); H. Tabor (Helen); B.C. Jacobs (Bart); K.A. Talukder (Kaisar); H.P. Endtz (Hubert)

    2009-01-01

    textabstractBackground: Campylobacter jejuni is a common cause of acute gastroenteritis and is associated with post-infectious neuropathies such as the Guillain-Barré syndrome (GBS) and the Miller Fisher syndrome (MFS). We here present comparative genotyping of 49 C. jejuni strains from Bangladesh t

  11. Blood group genotyping: from patient to high-throughput donor screening

    NARCIS (Netherlands)

    B. Veldhuisen; C.E. van der Schoot; M. de Haas

    2009-01-01

    Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human platele

  12. Molecular Epidemiology of Brucella Genotypes in Patients at a Major Hospital in Central Peru

    NARCIS (Netherlands)

    K. Noeckler; R. Maves; D. Cepeda; A. Draeger; A. Mayer-Scholl; J. Chacaltana; M. Castaneda; B. Espinosa; R. Castillo; E. Hall; S. Al Dahouk; R.H. Gilman; F. Cabeza; H.L. Smits

    2009-01-01

    The multiple-locus variable-number repeat analysis of 90 human Brucella melitensis isolates from a large urban area in central Peru revealed variations at 4 (Bruce07, Bruce09, Bruce18, and Bruce42) out of 16 loci investigated, of which 1 (Bruce42) also is used for species identification. Ten genotyp

  13. Estimation of tamoxifen metabolite concentrations in the blood of breast cancer patients through CYP2D6 genotype activity score.

    Science.gov (United States)

    Wu, Alan H B; Lorizio, Wendy; Tchu, Simone; Lynch, Kara; Gerona, Roy; Ji, Wuyang; Ruan, Weiming; Ruddy, Kathryn J; Desantis, Stephen D; Burstein, Harold J; Ziv, Elad

    2012-06-01

    Tamoxifen, a prodrug used for adjuvant breast cancer therapy, requires conversion to the active metabolite endoxifen through CYP 2D6. We aimed to construct an algorithm to predict endoxifen concentrations based on a patient’s CYP 2D6 genotype, demographic factors, and co-medication use. Eighty-eight women enrolled in the UCSF TamGen II study and 81 women enrolled in a prospective study at Dana-Farber Cancer Institute were included in this analysis. All the women had been on tamoxifen for at least 3 months before blood collection. Demographic information included the patient’s age, race/ethnicity, body mass index (where available), and self-reported and measured medications and herbals that affect 2D6 activity. DNA was extracted and genotyped for 2D6 (Amplichip, Roche Diagnostics). An activity score was calculated based on genotypes and adjusted for use of medications known to inhibit 2D6. Serum was tested for tamoxifen and metabolite concentrations and for the presence of drugs by liquid chromatography/mass spectrometry. Univariate and multivariate regression analysis were computed for age, body mass index, ethnicity, and adjusted activity score to predict tamoxifen metabolite concentrations in the training data-set of UCSF patients, and the resulting algorithm was validated in the Dana-Farber patients. For the training set, the correlation coefficient (r2) for log endoxifen and N-desmethyltamoxifen:endoxifen ratio to activity score, age, and race, were 0.520 and 0.659, respectively; 0.324 and 0.567 for the validation; and 0.396 and 0.615 for both the datasets combined. An algorithm that incorporates genotype and demographic variables can be used to predict endoxifen concentrations for women on tamoxifen therapy. If endoxifen levels are confirmed to be predictive of tamoxifen benefit, then this algorithm may be helpful to determine which women warrant endoxifen testing.

  14. Retreatment with peg-interferon and ribavirin in patients with chronic hepatitis C virus genotype 2 or 3 infection with prior relapse

    DEFF Research Database (Denmark)

    Lagging, Martin; Rembeck, Karolina; Rauning Buhl, Mads

    2013-01-01

    Uncertainty remains regarding the efficacy of retreatment with current standard-of-care peg-interferon (peg-IFN) and ribavirin among patients infected with hepatitis C virus (HCV) genotypes 2 or 3 with relapse after prior therapy....

  15. Genotyping of Toxoplasma gondii: DNA extraction from formalin-fixed paraffin-embedded autopsy tissues from AIDS patients who died by severe disseminated toxoplasmosis.

    Science.gov (United States)

    Bastos da Silva, Inara; Batista, Tatiana Pimental de Andrade; Martines, Roosecelis Brasil; Kanamura, Cristina Takami; Ferreira, Isabelle Martins Ribeiro; Vidal, Jose Ernesto; Pereira-Chioccola, Vera Lucia

    2016-06-01

    This study investigated the genetic features of Toxoplasma gondii isolated directly in autopsies of HIV-infected patients who died with severe disseminated toxoplasmosis. This retrospective analysis was conducted in a cohort of 15 HIV-infected patients with clinical and laboratory data. They had previous cerebral toxoplasmosis at least 6 months before the disseminated toxoplasmosis episode. The hypothesis was that they were infected with highly virulent parasites due to the condition in which they died. T. gondii genotyping was done directly in DNA extracted from 30 autopsy brain and lung samples (2 per patient) and mutilocus PCR-RFLP genotyping was done using 12 molecular markers. The 30 clinical samples were genotyped successfully in 8 or more loci and six suggestive genotypes were identified. One of them was Toxo DB #11, previously identified in different domestic animals and virulent in experimental animals. The other five suggestive genotypes identified in 14 patients were not described. TgHuDis1 was the most frequent and was determined in 8 patients. TgHuDis3 and TgHuDis5 were identified in two patients each. TgHuDis2 and TgHuDis4 have been identified in one patient each. These suggestive genotypes could be considered as virulent, since they caused severe tissue damage and had similar characteristics as Toxo # DB 11.

  16. Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection

    DEFF Research Database (Denmark)

    Pedersen, C; Alsiö, Å; Lagging, M

    2011-01-01

    Summary. In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin...... is generally recommended. The primary aim of this study was to investigate the correlation between ribavirin concentration at day 29 and therapeutic response in patients with HCV genotype 2/3 infection. A total of 382 patients were randomized to 12 or 24 weeks of treatment with pegylated interferon-alfa 2a 180...

  17. Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin

    Institute of Scientific and Technical Information of China (English)

    María Trapero-Marugán; Jorge Mendoza; María Chaparro; Leticia González-Moreno; José Andrés Moreno-Monteagudo

    2011-01-01

    AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SVR) after peginterferon (PEG-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SVR after treatment with PEG-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SVR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SVR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SVR to PEG-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

  18. Impact of host IL28B rs12979860, rs8099917 in interferon responsiveness and advanced liver disease in chronic genotype 3 hepatitis C patients.

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    Rushna Firdaus

    Full Text Available BACKGROUND AND AIMS: Genetic polymorphisms near interleukin 28B gene are associated with spontaneous and treatment induced clearance of hepatitis C virus (HCV. Our objective was to evaluate the impact of interleukin 28B single nucleotide polymorphism (rs12979860, rs8099917 variability in HCV genotype 3 infected populations. METHODS: 400 hepatitis C seroreactive patients from different population groups in Eastern and North Eastern part of India were assessed for host and viral genotypic analysis. 83 HCV genotype 3 infected patients were administered pegylated interferon- ribavirin therapy. Viral genotyping was performed using nested reverse transcriptase-PCR followed by direct sequencing methods. Host interleukin 28B genotyping was performed using real-time PCR based single nucleotide polymorphism analysis. RESULTS: Out of 400 hepatitis C seroreactive individuals, 73.25% were found to be RNA positive. HCV genotype 3 (65.87% was found to be the major circulating strain in this region followed by genotype 1 (32.08%. rs12979860 CC genotype was significantly associated with sustained virological response in HCV genotype 3 infected population. In patients achieving rapid virological response, favourable CC/TT allele at rs12979860, rs8099917 was found to be predominant at both the alleles at 77%, 73.2% respectively; whereas in case of patients with relapsed HCV infection CT, TG alleles were found to be predominant. Additionally, CC genotypes at rs12979860 were found to be associated with sustained virological response in patients with high viral load (OR = 6.75, 0.05patients with relapsed HCV infection respectively. Also unfavourable CT, TG genotypes were found to be predominant in patients with advanced stages of liver disease. CONCLUSION: CC, TT the two favourable markers at SNPs rs12979860 and rs8099917 are strongly associated with sustained virological response

  19. Distinct patterns of the lipid alterations between genotype 1 and 2 chronic hepatitis C patients after viral clearance.

    Directory of Open Access Journals (Sweden)

    Ming-Ling Chang

    Full Text Available The hepatitis C virus (HCV genotype-specific impacts on the host metabolic alterations remained inconclusive.A prospective study including 229 (118 genotype 1 (G1 and 111 G2 consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR ≥ 2.5. Paired t-tests were used to compare the pre- and post-treatment variables.Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001 and apolipoprotein A1 (p = 0.012 were only found in G2, whereas increased triglyceride/HDL (p = 0.01 ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019 and apolipoprotein A1 (p = 0.012 but a decrease in HOMA-IR (p = 0.04, C-peptide (p = 0.019 and hemoglobin A1c (p = 0.047 were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002 was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01 but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041 and triglyceride (p = 0.044 levels than G2 patients.G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR.

  20. Phenotype and Genotype in a Cohort of 312 Adult Patients with Nontransfusion-Dependent Thalassemia in Northeast Thailand.

    Science.gov (United States)

    Prayalaw, Patcharawadee; Teawtrakul, Nattiya; Jetsrisuparb, Arunee; Pongudom, Saranya; Fucharoen, Goonnapa; Fucharoen, Supan

    2016-01-01

    Patients with nontransfusion-dependent thalassemia (NTDT) do not require regular blood transfusion for survival but may encounter several complications that contribute to morbidity and mortality. We report the molecular heterogeneity and hematological features of NTDT in 312 adult patients in northeast Thailand. Hemoglobin (Hb) and DNA analyses identified 177 subjects with Hb E-β-thalassemia, 1 with homozygous β0-thalassemia and 134 with Hb H, AEBart's and EEBart's diseases. For β-thalassemia, 12 different mutations including both β0- and β+-thalassemias were detected. Coinheritance of α-thalassemia as an ameliorating factor was observed in 18 of 178 cases (10.1%) with β-thalassemia. The α-globin gene triplicated haplotype (αααanti3.7) was observed in 1 case of Hb E-β0-thalassemia. The presence of the -158 (Cx2192;T) Gx03B3;-XmnI polymorphism (+/+) was found to be associated with increased Hb F expression, but its frequency in the studied subjects was low. Those with α-thalassemia included 17 with deletional and 51 nondeletional Hb H, and 63 with AEBart's and 3 with EEBart's diseases. The hematological parameters of these NTDT and genotype-phenotype relationships are presented. The diverse molecular heterogeneity of NTDT underlines the importance of complete genotyping of the patient. These results should prove useful for management planning, the prediction of clinical outcome and to improve genetic counseling for NTDT patients. © 2015 S. Karger AG, Basel.

  1. Multiple isolates from Aids patients: aspects of an analysis by a genotypic marker and antimicrobial susceptibilities variations

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    Maria Helena Féres Saad

    2000-10-01

    Full Text Available Twenty-one Mycobacterium avium multisolates, from ten human immunodeficiency virus-infected patients, were typed by restriction fragment length polymorphism using as marker the IS1245 and characterized by minimum inhibitory concentration for nine different antibiotics. Two out of four patients harboring multisolates with different fingerprint profile, were therefore considered as having a polyclonal infection, since their isolates were taken from sterile site. This result confirms that polyclonal infection caused by M. avium occurs with a nonnegligenciable frequency. Analyzing the multisolates susceptibility profile of each patient it was observed that most of them were infected with strains having appreciably different antimicrobial susceptibility patterns, no matter what the genotypic pattern of the strains was. These results have strong implication for the treatment of the patients.

  2. ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Færch, Louise H; Sejling, Anne-Sophie; Lajer, Maria

    2015-01-01

    AIMS: Carrying the D-allele of the angiotensin-converting enzyme (ACE) I/D polymorphism and high ACE activity are prognostic factors in diabetic nephropathy, which predicts mortality in type 1 diabetes. We studied the association between the ACE D-allele and ACE phenotype and long-term all......-cause mortality in three single-institution outpatient cohorts. METHODS: Genotype-based analyses were performed in 269 patients from Hillerød Hospital (HIH) (follow-up: 12 years) and in 439 patients with diabetic nephropathy and 437 patients with persistent normoalbuminuria from the Steno Diabetes Center (SDC......) (follow-up: 9.5 years). Patients not on renin-angiotensin system (RAS)-blocking treatment were included in analyses of serum ACE activity (HIH: n = 208) and plasma ACE concentration (SDC: n=269). RESULTS: In the HIH cohort, carrying a D-allele was associated with excess mortality (hazard ratio (HR) = 4...

  3. Phenotypic and genotypic detection of Candida albicans and Candida dubliniensis strains isolated from oral mucosa of AIDS pediatric patients.

    Science.gov (United States)

    Livério, Harisson Oliveira; Ruiz, Luciana da Silva; Freitas, Roseli Santos de; Nishikaku, Angela; Souza, Ana Clara de; Paula, Claudete Rodrigues; Domaneschi, Carina

    2017-04-13

    The aim of this study was to assess a collection of yeasts to verify the presence of Candida dubliniensis among strains isolated from the oral mucosa of AIDS pediatric patients which were initially characterized as Candida albicans by the traditional phenotypic method, as well as to evaluate the main phenotypic methods used in the discrimination between the two species and confirm the identification through genotypic techniques, i.e., DNA sequencing. Twenty-nine samples of C. albicans isolated from this population and kept in a fungi collection were evaluated and re-characterized. In order to differentiate the two species, phenotypic tests (Thermotolerance tests, Chromogenic medium, Staib agar, Tobacco agar, Hypertonic medium) were performed and genotypic techniques using DNA sequencing were employed for confirmation of isolated species. Susceptibility and specificity were calculated for each test. No phenotypic test alone was sufficient to provide definitive identification of C. dubliniensis or C. albicans, as opposed to results of molecular tests. After amplification and sequencing of specific regions of the 29 studied strains, 93.1% of the isolates were identified as C. albicans and 6.9% as C. dubliniensis. The Staib agar assay showed a higher susceptibility (96.3%) in comparison with other phenotypic techniques. Therefore, genotypic methods are indispensable for the conclusive identification and differentiation between these species.

  4. Hepatic fibrosis in patients with chronic hepatitis C assessed by transient elastography: implications for determining the efficacy of antiviral therapy Evaluación de la fibrosis hepática en pacientes con hepatopatía crónica C mediante elastografía transitoria: implicaciones para determinar la eficacia del tratamiento antiviral

    Directory of Open Access Journals (Sweden)

    J. Mendoza

    2010-07-01

    Full Text Available Background: the efficacy of combination therapy with peginterferon plus ribavirin to eradicate viral infection in patients with chronic hepatitis C (CHC is well established; moreover, it is able to arrest or even reverse liver fibrosis. Aims: to analyze the measurements of hepatic stiffness as an index of liver fibrosis using transient elastography (TE in patients who underwent a sustained virological response (SVR during long-term follow-up; comparing the changes in the severity of fibrosis with non-responders patients. Material and methods: after hepatic fibrosis was studied in three patients with CHC who underwent a SVR during long-term follow up, a prospective study was initiated in 24 patients with CHC who received combination therapy to compare the evolution of fibrosis in those with SVR and those who were non-responders. The genotype of hepatitis C virus (HCV and the degree of viremia were determined. METAVIR scoring system was used for liver fibrosis. Hepatic stiffness was measured by TE. Results: of the initial three patients pre-treatment liver biopsies revealed active disease and fibrosis (stage 3 in two and mild fibrosis (stage 1 in one. After several years of follow up serum AST/ALT levels were normal and HCV RNA was undetectable in each case; in contrast to the baseline histological assessments of fibrosis, values for hepatic stiffness (3.4-6.9 KPa were compatible with an absence of any appreciable hepatic fibrosis. In the prospective study, 8 patients underwent a SVR and 16 were non-responders. TE indicated that the severity of hepatic fibrosis in the SVR group improved in 7 (88% patients, whereas in the non-responder it improved in only 4 (25% (p < 0.05. The difference between development of severe fibrosis (F ≥ 3 in responders and non-responders was not significant (p = 0.23, possibly due to the small sample size. Conclusions: regression of hepatic fibrosis appears to be common in patients with CHC who undergo a SVR. TE is a

  5. Sofosbuvir-Based Therapy for Genotype 4 HCV Recurrence Post-Liver Transplant Treatment-Experienced Patients

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    A. Ajlan

    2016-01-01

    Full Text Available Background and Aim. This is an open label prospective cohort study conducted at a tertiary care hospital. The primary endpoint is SVR12 in patients treated with sofosbuvir-based therapy in post-liver transplant patients with genotype 4 HCV recurrence. Methodology. Thirty-six treatment-experienced liver transplant patients with HCV recurrence received sofosbuvir and ribavirin ± peginterferon. Results. We report here safety and efficacy data on 36 patients who completed the follow-up period. Mean age was 56 years, and the cohort included 24 males and one patient had cirrhosis. Mean baseline HCV RNA was 6.2 log10 IU/mL. The majority of patients had ≥ stage 2 fibrosis. Twenty-eight patients were treated with pegylated interferon plus ribavirin in addition to sofosbuvir for 12 weeks and the remaining were treated with sofosbuvir plus ribavirin only for 24 weeks. By week 4, only four (11.1% patients had detectable HCV RNA. Of the 36 patients, 2 (5.5% relapsed and one died (2.75%. Conclusion. Our results suggest that sofosbuvir + ribavirin ± pegylated interferon can be utilized successfully to treat liver transplant patients with HCV recurrence.

  6. Sofosbuvir-Based Therapy for Genotype 4 HCV Recurrence Post-Liver Transplant Treatment-Experienced Patients

    Science.gov (United States)

    Ajlan, A.; Al-Jedai, A.; Elsiesy, H.; Alkortas, D.; Al-Hamoudi, W.; Alarieh, R.; Al-Sebayel, M.; Broering, D.; Aba Alkhail, F.

    2016-01-01

    Background and Aim. This is an open label prospective cohort study conducted at a tertiary care hospital. The primary endpoint is SVR12 in patients treated with sofosbuvir-based therapy in post-liver transplant patients with genotype 4 HCV recurrence. Methodology. Thirty-six treatment-experienced liver transplant patients with HCV recurrence received sofosbuvir and ribavirin ± peginterferon. Results. We report here safety and efficacy data on 36 patients who completed the follow-up period. Mean age was 56 years, and the cohort included 24 males and one patient had cirrhosis. Mean baseline HCV RNA was 6.2 log10 IU/mL. The majority of patients had ≥ stage 2 fibrosis. Twenty-eight patients were treated with pegylated interferon plus ribavirin in addition to sofosbuvir for 12 weeks and the remaining were treated with sofosbuvir plus ribavirin only for 24 weeks. By week 4, only four (11.1%) patients had detectable HCV RNA. Of the 36 patients, 2 (5.5%) relapsed and one died (2.75%). Conclusion. Our results suggest that sofosbuvir + ribavirin ± pegylated interferon can be utilized successfully to treat liver transplant patients with HCV recurrence. PMID:27446833

  7. A type-specific nested PCR assay established and applied for investigation of HBV genotype and subgenotype in Chinese patients with chronic HBV infection

    Directory of Open Access Journals (Sweden)

    Nie Jing-Jing

    2012-06-01

    Full Text Available Abstract Background Many studies have suggested that hepatitis B virus (HBV genotypes show not only geographical distribution and race specificity, but also are associated with disease progression and response to interferon treatment. The objective of this study was to develop a nested polymerase chain reaction (nPCR assay for genotypes A-D and subgenotypes B1, B2, C1 and C2 of hepatitis B virus (HBV and to investigate the distribution characteristics of HBV genotypes/subgenotype in China. Methods After redesigning the primers and optimizing the reaction conditions using common Taq polymerase, the sensitivity, specificity and reproducibility of the method were evaluated using plasmids and serum samples. In total, 642 serum samples from patients with chronic HBV infection were applied to investigate the distribution of HBV genotype and subgenotype in China. Results The genotype and subgenotype could be identified when the HBV DNA load of a sample was ≥102.3 IU/mL. For the 639 successfully genotyped samples, the sequencing results of 130 randomly selected samples (20.3%, 130/639 were consistent with those of the nPCR method. The present study showed that HBV genotype B (11.2%, 72/642, C (68.2%, 438/642 and D (7.2%, 46/642 were circulating in China, while genotype C was the dominant strain except for western region where genotype D was the prevalent strain. The main subgenotypes of genotypes B and C were B2 (87.5%, 63/72 and C2 (92.9%, 407/438, respectively. Conclusions The low-cost nPCR method would be a useful tool for clinical and epidemiological investigation in the regions where genotypes A-D are predominant.

  8. Helicobacter pylori vacA and cagA genotype diversity and interferon gamma expression in patients with chronic gastritis and patients with gastric cancer.

    Science.gov (United States)

    Martínez-Carrillo, D N; Atrisco-Morales, J; Hernández-Pando, R; Reyes-Navarrete, S; Betancourt-Linares, R; Cruz-del Carmen, I; Illades Aguiar, B; Román-Román, A; Fernández-Tilapa, G

    2014-01-01

    Helicobacter pylori (H. pylori) is the main risk factor for the development of chronic gastritis, gastric ulcer, and gastric cancer. In H. pylori-infected individuals, the clinical result is dependent on various factors, among which are bacterial components, the immune response, and environmental influence. To compare IFN-γ expression with the H. pylori vacA and cagA genotypes in patients with chronic gastritis and patients with gastric cancer. Ninety-five patients diagnosed with chronic gastritis and 20 with gastric cancer were included in the study. Three gastric biopsies were taken; one was used for the molecular detection and genotyping of H. pylori; another was fixed in absolute alcohol and histologic sections were made for determining IFN-γ expression through immunohistochemistry. No differences were found in the cells that expressed IFN-γ between the patients with chronic gastritis (median percentage of positive cells: 82.6% in patients without H. pylori and 82% in infected persons) and those with gastric cancer (70.5% in H. pylori-negative patients and 78.5% in infected persons). IFN-γ expression was 69% in chronic gastritis patients infected with H. pylori vacAs2m2/cagA⁻ it was 86.5% in patients infected with H. pylori vacAs1m2/cagA⁻, 86.5% in vacAs1m1/cagA⁻, and 82% in vacAs1m1/cagA⁺. Similar data were found in the patients with gastric cancer. IFN-γ expression varied depending on the H. pylori vacA and cagA genotype, but not in accordance with the presence of chronic gastritis or gastric cancer.

  9. Mix-infections with different genotypes of HCV and with HCV plus other hepatitis viruses in patients with hepatitis C in China

    Institute of Scientific and Technical Information of China (English)

    Yuan-Ding Chen; Ming-Ying Liu; Wen-Lin Yu; Jia-Qi Li; Qin Dai; Zhen-Quan Zhou; Sergio G. Tisminetzky

    2003-01-01

    AIM: Clinical therapy and prognosis in HCV infections are not good, and mix-infections with different HCV genotypes or quasispecies and mix-infections with HCV plus other hepatitis viruses are important concerns worldwide. The present report describes the sequence diversity and genotying of the 5'NCR of HCV isolates from hepatitis patients mix-infected with different HCV genotypes or variants, and the conditions of mix-infections with HCV plus other hepatitis viruses, providing important diagnostic and prognostic information for more effective treatment of HCV infections.METHODS: The 5' non-coding region (5'NCR) of HCV was isolated from the patients sera and sequenced, and sequence variability and genotypes of HCV were defined by nucleotide sequence alignment and phylogenetic analysis, and the patients mix-infected with HCV plus other hepatitis viruses were analyzed. The conditions and clinical significance of mix-infections with HCV plus other hepatitis viruses were further studied.RESULTS: Twenty-four out of 43 patients with chronic hepatitis C were defined as mix-infected with different genotypes of HCV. Among these 24 patients, 9 were mixinfected with genotype 1 and 3, 7 with different variants of genotype 1, 2 with different variants of genotype 2, 6with different variants of genotype 3. No patients were found mix-infected with genotype 1 and 2 or with genotype 2 and 3. The clinical virological analysis of 60 patients mixinfected with HCV plus other hepatitis viruses showed that 45.0 % of the patients were mix-infected with HCV plus HAV, 61.7 % with HCV plus HBV, 6.7 % with HCV plus HDV/HBV, 8.4 % with HCV plus HEV, 3.3 % with HCV plus HGV. Infections with HCV plus other hepatitis viruses may exacerbate the pathological lesion of the liver.CONCLUSION: The findings in the present study imply that mix-infections with different HCV genotypes and mixinfections with HCV plus other hepatitis viruses were relatively high in Yunnan, China, providing important

  10. New Insights into Genotype-phenotype Correlations in Chinese Facioscapulohumeral Muscular Dystrophy: A Retrospective Analysis of 178 Patients

    Institute of Scientific and Technical Information of China (English)

    Feng Lin; Zhi-Qiang Wang; Min-Ting Lin; Shen-Xing Murong; Ning Wang

    2015-01-01

    Background:Facioscapulohumeral muscular dystrophy (FSHD),a common autosomal dominant muscular disorder,is caused by contraction of the D4Z4 repeats on 4q35.The complicated genotype-phenotype correlation among different ethnic population remains a controversial subject.We aimed to refine this correlation in order to provide new information for genetic counseling.Methods:Here,a cohort of 136 Chinese families including 178 affected individuals and 137 unaffected members were investigated.Genetic analyses were performed using the pl3E-11,4qA and 4qB probes after pulsed field gel electrophoresis separation and southern blotting.A 10-grade FSHD clinical severity scale was adopted for clinical assessment.The genotype-phenotype correlation was established by linear regression analyses.Results:We observed a roughly inversed correlation between the short EcoRI fragment size and age-corrected clinical severity score in 154 symptomatic patients (P < 0.05).Compared to male patients,a significant higher proportion of females in both asymptomatic carriers and severe patients showed larger variation in the size of short EcoRI fragment.A high incidence (19/42,45.2%) of asymptomatic (or minimally affected) carriers was found in familial members.Conclusions:Although the number of D4Z4 repeats is known as one of the critical influences on genotype-phenotype correlation,a majority of phenotypic spectrum was still incompatible with their heterozygous contraction of the D4Z4 repeat,especial in female cases.Our results suggest that there are multi-factors synergistically modulating the phenotypic expression.

  11. Genotype-Phenotype Correlation of SMN1 and NAIP Deletions in Korean Patients with Spinal Muscular Atrophy

    Science.gov (United States)

    Ahn, Eun-Ji; Yum, Mi-Sun; Kim, Eun-Hee; Yoo, Han-Wook; Lee, Beom Hee; Kim, Gu-Hwan

    2017-01-01

    Background and Purpose Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscle weakness and atrophy. Most SMA patients have a homozygous deletion in survival of motor neuron 1 (SMN1) gene, and neuronal apoptosis inhibitory protein (NAIP) gene is considered a phenotype modifier. We investigated the genotype-phenotype correlation of SMN1 and NAIP deletions in Korean SMA patients. Methods Thirty-three patients (12 males and 21 females) treated at the Asan Medical Center between 1999 and 2013 were analyzed retrospectively. The polymerase chain reaction (PCR), restriction-fragment-length polymorphism analysis, and multiplex PCR were used to detect deletions in SMN1 (exons 7 and 8) and NAIP (exons 4 and 5). We reviewed clinical presentations and outcomes and categorized the patients into three clinical types. NAIP deletion-driven differences between the two genotypes were analyzed. Results Deletion analysis identified homozygous deletions of SMN1 exons 7 and 8 in 30 patients (90.9%). Among these, compared with patients without an NAIP deletion, those with an NAIP deletion showed a significantly lower age at symptom onset (1.9±1.7 months vs. 18.4±20.4 months, mean±SD; p=0.007), more frequent type 1 phenotype (6/6 vs. 8/24, p=0.005), and worse outcomes, with early death or a requirement for ventilator support (4/4 vs. 2/12, p=0.008). Conclusions Homozygous deletion in SMN1 and a concurrent NAIP deletion were associated with an early onset, severe hypotonia, and worse outcome in SMA patients. Deletion analysis of NAIP and SMN1 can help to accurately predict prognostic outcomes in SMA. PMID:27730768

  12. [Lymphocyte metabolism in patients with acute pancreatitis with different genotypes of GSTM1 and GSTT1 genes].

    Science.gov (United States)

    Markova, E V; Zotova, N V; Savchenko, A A; Titova, N M; Slepov, E V; Cherdantsev, D V; Konovalenko, A N

    2006-01-01

    In this study, we have investigated correlation between enzymatic activity of NAD(P)-dependent dehydrogenases of lymphocytes and polymorphic variants of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genes in the group of unrelated patients with acute pancreatitis in comparison with healthy Russians from Krasnoyarsk. Thus, genotype GSTM1 0/0 is the marker of predisposition to the acute pancreatitis, wheras polymorphism of the GSTT1 gene is not involved in the development of the pancreatitis, at least in our group. The bioluminescence analysis showed statistically significant decrease of the levels of G3PD, NAD(+)MDH and the increase of NADH(+)LDH, NAD(+)GDH, NADH(+)GDH in lymphocytes of pancreatic group. Development of pancreatitis in patients with different genotypes GSTM1 and GSTT1 genes showed the rearrangement of the basic intracellular processes: dominance of a plastic metabolism in the patients with GSTM1--deletions and predominance of energetic processes at GSTT1 0 - pancreatitis.

  13. vacA genotypes of Helicobacter pylori in the oral cavity and stomach of patients with chronic gastritis and gastric ulcer.

    Science.gov (United States)

    Román-Román, Adolfo; Giono-Cerezo, Silvia; Camorlinga-Ponce, Margarita; Martínez-Carrillo, Dinorah Nashely; Loaiza-Loeza, Salome; Fernández-Tilapa, Gloria

    2013-03-01

    Helicobacter pylori adheres to various components of the human saliva. Therefore, the objective of this research was to simultaneously detect H. pylori in saliva and in gastric biopsy, and to determine the agreement between the vacA genotypes in both saliva and gastric biopsy. A total of 162 patients with chronic gastritis and 34 with gastric ulcer were studied, and saliva and biopsy samples were collected from each patient. H. pylori DNA was detected by conventional PCR and nested PCR was used for vacA genotyping. In 24% of the patients (47/196) H. pylori DNA was found in saliva and in biopsy; 52.5% (103/196) were saliva(negative)/biopsy(positive) and 6.6% (13/196) were saliva(positive)/biopsy(negative). In either or both H. pylori vacAs1m1 or s1m2 genotypes were detected in saliva in 41.5% of the patients with chronic gastritis. Forty-seven percent had >1 genotype, and the s1m1/s1m2 combination was found in 36% of them. H. pylori vacAs1m1 and s1m2 were also found in the saliva and biopsy of patients with gastric ulcer. The genotypes found in saliva and biopsy of the same patient had 51.1% agreement. In 27.6% of the 47 patients saliva(positive)/biopsy(positive) two genotypes were found in saliva, and one or both in the stomach. The s1m1/s1m2 genotypes, alone or together, are found simultaneously in saliva and gastric biopsy of the same patient. These results suggest that H. pylori reaches the oral cavity by various ways, and that saliva can be the transmitting and re-infecting vector. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  14. Outbreak of infections by hepatitis B virus genotype A and transmission of genetic drug resistance in patients coinfected with HIV-1 in Japan.

    Science.gov (United States)

    Fujisaki, Seiichiro; Yokomaku, Yoshiyuki; Shiino, Teiichiro; Koibuchi, Tomohiko; Hattori, Junko; Ibe, Shiro; Iwatani, Yasumasa; Iwamoto, Aikichi; Shirasaka, Takuma; Hamaguchi, Motohiro; Sugiura, Wataru

    2011-03-01

    The major routes of hepatitis B virus (HBV) infection in Japan has been mother-to-child transmission (MTCT) and blood transfusion. However, HBV cases transmitted through sexual contact are increasing, especially among HIV-1-seropositive patients. To understand the molecular epidemiology of HBV in HBV/HIV-1 coinfection, we analyzed HBV genotypes and HIV-1 subtypes in HBV/HIV-1-coinfected patients at Nagoya Medical Center from 2003 to 2007. Among 394 HIV-1-infected Japanese men having sex with men (MSM) who were newly diagnosed during the study period, 31 (7.9%) tested positive for the hepatitis B virus surface antigen. HBV sequence analyses were successful in 26 cases, with 21 (80.7%) and 5 (19.3%) cases determined as genotypes A and C, respectively. Our finding that HBV genotype A was dominant in HIV-1-seropositive patients alerts clinicians to an alternative outbreak of HBV genotype A in the HIV-1-infected MSM population and a shift in HBV genotype from C to A in Japan. The narrow genetic diversity in genotype A cases suggests that genotype A has been recently introduced into the MSM population and that sexual contacts among MSM were more active than speculated from HIV-1 tree analyses. In addition, we found a lamivudine resistance mutation in one naïve case, suggesting a risk of drug-resistant HBV transmission. As genotype A infection has a higher risk than infection with other genotypes for individuals to become HBV carriers, prevention programs are urgently needed for the target population.

  15. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, Louise B; Kronborg, Gitte

    2007-01-01

    OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients...... with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic...

  16. Towards a genotype-based approach for a patient-centered pharmacologic therapy of type 2 diabetes.

    Science.gov (United States)

    Scheen, André J

    2015-05-01

    The recent data reported by Tang and colleagues in Science Translational Medicine suggest that alpha-2 adrenoceptors (α2AAR) genetic heterogeneity may explain diverging results regarding the effects of α2AAR antagonists on insulin secretion and glucose control in patients with type 2 diabetes. They first confirmed that the risk variant for rs553668 (the A allele for a single-nucleotide polymorphism in ADRA2A) is likely to cause defective insulin secretion in human pancreatic islets. Second they showed that blocking α2AAR with yohimbine dose-dependently improves the reduced insulin secretion during an oral glucose tolerance test in patients with the risk variant. The successful translation of genomic information into clinical intervention in patients with type 2 diabetes provides proof of concept for the feasibility of individualized treatment based on genotype.

  17. Interleukin 28B gene variation at rs12979860 determines early viral kinetics during treatment in patients carrying genotypes 2 or 3 of hepatitis C virus

    DEFF Research Database (Denmark)

    Lindh, Magnus; Lagging, Martin; Färkkilä, Martti

    2011-01-01

    Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon λ3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n...... years (P = .01). Patients carrying CC(rs12979860) had higher baseline HCV RNA levels (P 12 weeks, achieve sustained virologic response more often than those carrying CT(rs1297986) or TT(rs1297986). The results indicate that IL28B gene testing may identify patients...

  18. Differing von Hippel Lindau genotype in paired primary and metastatic tumors in patients with clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Susan A.J. Vaziri

    2012-05-01

    Full Text Available In sporadic clear cell renal cell carcinoma (CCRCC, the von Hippel Lindau (VHL gene is inactivated by mutation or methylation in the majority of primary (P tumors. Due to differing effects of wild-type (WT and mutant (MT VHL gene on downstream signaling pathways regulating angiogenesis, VHL gene status could impact clinical outcome. In CCRCC, comparative genomic hybridization (CGH analysis studies have reported genetic differences between paired P and metastatic (M tumors. We thus sequenced the VHL gene in paired tumor specimens from 10 patients to determine a possible clonal relationship between the P tumor and M lesion(s in patients with CCRCC. Using paraffin embedded specimens, genomic DNA from microdissected samples (>80% tumor of paired P tumor and M lesions from all 10 patients, as well as in normal tissue from 6 of these cases, was analyzed. The DNA was used for PCR-based amplification of each of the 3 exons of the VHL gene. Sequences derived from amplified samples were compared to the wild-type VHL gene sequence (GeneBank Accession No. AF010238. Methylation status of the VHL gene was determined using VHL methylation-specific PCR primers after DNA bisulfite modification. In 4/10 (40% patients the VHL gene status differed between the P tumor and the M lesion. As expected, when the VHL gene was mutated in both the P tumor and M lesion, the mutation was identical. Further, while the VHL genotype differed between the primary tumor in different kidneys or multiple metastatic lesions in the same patient, the VHL germline genotype in the normal adjacent tissue was always wild-type irrespective of the VHL gene status in the P tumor. These results demonstrate for the first time that the VHL gene status can be different between paired primary and metastatic tissue in patients with CCRCC.

  19. Helicobacter pylori vacA and cagA genotypes in patients from northeastern Brazil with upper gastrointestinal diseases

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    Meyssa Quezado de Figueiredo Cavalcante

    2012-06-01

    Full Text Available Helicobacter pylori causes chronic gastric inflammation and significantly increases the risk of duodenal and gastric ulcer disease and distal gastric carcinoma. In this study, we evaluated the Helicobacter pylori vacA and cagA genotypes in patients from a Brazilian region where there is a high prevalence of gastric cancer. Polymerase chain reaction (PCR was used to investigate vacA mosaicism and cagA status in the gastric mucosa of 134 H. pylori-positive patients, including 76 with gastritis: 28 with peptic ulcer disease and 30 with gastric cancer. The s1m1 variant was the predominant vacA genotype observed, whereas the s1 allele was more frequently observed in patients with more severe diseases associated with H. pylori infection [p = 0.03, odds ratio (OR = 5.72, 95% confidence interval (CI = 1.15-38.60]. Furthermore, all of the s1 alleles were s1b. Mixed vacA m1/m2 strains were found more frequently in patients with gastric cancer and a cagA-positive status was significantly associated with gastric cancer (p = 0.016, OR = 10.36, 95% CI = 1.35-217.31. Patients with gastric cancer (21/21, 100%, p = 0.006 or peptic ulcers (20/21, 95%, p = 0.02 were more frequently colonised by more virulent H. pylori strains compared to gastritis patients (41/61, 67.2%. In conclusion, in the northeastern of Brazil, which is one of the regions with the highest prevalence of gastric cancer in the country, infection with the most virulent H. pylori strains, carrying the cagA gene and s1m1 vacA alleles, predominates and is correlated with more severe H. pylori-associated diseases.

  20. Cardiovascular disease in patients with genotyped familial hypercholesterolemia in Norway during 1994-2009, a registry study.

    Science.gov (United States)

    Mundal, Liv; Veierød, Marit B; Halvorsen, Thomas; Holven, Kirsten B; Ose, Leiv; Iversen, Per Ole; Tell, Grethe S; Leren, Trond P; Retterstøl, Kjetil

    2016-12-01

    Background Familial hypercholesterolaemia increases the risk for cardiovascular disease. The primary aim of the present study was to describe sex differences in incidence and prevalence of cardiovascular disease leading to hospitalisation in a complete cohort of genotyped familial hypercholesterolaemia patients. Design and methods In this registry study data on 5538 patients with verified genotyped familial hypercholesterolaemia were linked to data on all Norwegian cardiovascular disease hospitalisations, and hospitalisations due to pre-eclampsia/eclampsia, congenital heart defects and diabetes. Results During 1994-2009 a total of 1411 of familial hypercholesterolaemia patients were hospitalised, and ischaemic heart disease was reported in 90% of them. Mean (SD) age at first hospitalisation and first re-hospitalisation was 45.1 (16.5) and 47.6 (16.3) years, respectively, with no sex differences ( P = 0.66 and P = 0.93, respectively). More men (26.9%) than women (24.1%) with familial hypercholesterolaemia were hospitalised ( P = 0.02). The median (25th-75th percentile) number of hospital admissions was four (two to seven) per familial hypercholesterolaemia patient, with no sex differences ( P = 0.87). Despite having familial hypercholesterolaemia at the time of hospitalisation, the diagnosis of familial hypercholesterolaemia was registered in only 45.7% of the patients at discharge. Conclusion Most cardiovascular disease hospitalisations were due to ischaemic heart disease. Familial hypercholesterolaemia patients were first time hospitalised at age 45.1 years, with no significant sex differences in age, which are important novel findings. The awareness and registration of the familial hypercholesterolaemia diagnosis during the hospital stays were disturbingly low.

  1. Novel subtypes (subgenotypes) of hepatitis B virus genotypes B and C among chronic liver disease patients in the Philippines.

    Science.gov (United States)

    Sakamoto, Tomoyuki; Tanaka, Yasuhito; Orito, Etsuro; Co, Jonard; Clavio, Joseph; Sugauchi, Fuminaka; Ito, Kiyoaki; Ozasa, Atsushi; Quino, Alvin; Ueda, Ryuzo; Sollano, Jose; Mizokami, Masashi

    2006-07-01

    Several hepatitis B virus (HBV) subtypes (subgenotypes), HBV/Aa (A1 : Asia/Africa), Ae (A2 : Europe), Bj (B1 : Japan) and Ba (B2 : Asia), have been reported with respect to clinical differences between patients infected with these subtypes (subgenotypes). HBV genotype distribution among patients with chronic liver diseases was investigated in the Philippines, where such studies have not been carried out previously. One hundred sera were obtained from such patients, consisting of 32 chronic hepatitis (CH), 37 cirrhosis and 31 hepatocellular carcinoma (HCC) patients. Nine complete genomes and 100 core promoter/precore genes of HBV were sequenced directly. Phylogenetic analyses revealed 51 HBV/A (Aa/A1), 22 HBV/B and 27 HBV/C strains. Interestingly, most HBV/C strains in the Philippines formed a specific cluster distinct from previous HBV/C strains (C1-4), indicating a novel subtype (subgenotype), HBV/C5. Moreover, most HBV/B strains fell within the specific cluster of the HBV/B subtype (subgenotype) B5, with viral characteristics of HBV/Ba (B2) carrying a recombination with HBV/C over the precore and core genes. Of the three genotypes, HBV/B and HBV/C were significantly more prevalent than HBV/A in cirrhosis and HCC patients (P<0.02). The prevalence of the core promoter mutations T1762/A1764 was higher in HCC patients with HBV/B and HBV/C. Multivariate analysis indicated that age [odds ratio (OR) 3.43; 95 % confidence interval (CI) 1.04-11.36; P=0.044] and the core promoter mutation (OR 14.08; 95% CI 3.62-4.74; P<0.001) were significant factors for HCC development. In conclusion, novel HBV subtypes (subgenotypes) C5 and B5 are prevalent in the Philippines, as well as HBV/Aa (A1).

  2. Sofosbuvir plus simeprevir for the treatment of HCV genotype 4 patients with advanced fibrosis or compensated cirrhosis is highly efficacious in real life.

    Science.gov (United States)

    Willemse, S B; Baak, L C; Kuiken, S D; van der Sluys Veer, A; Lettinga, K D; van der Meer, J T M; Depla, A C T M; Tuynman, H; van Nieuwkerk, C M J; Schinkel, C J; Kwa, D; Reesink, H W; van der Valk, M

    2016-12-01

    Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver-related death. Recently, multiple regimens of different direct-acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real-life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon-based treatment, and one was treatment naive. In this real-life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment-experienced patients as recommended in guidelines.

  3. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe

    DEFF Research Database (Denmark)

    Soriano, Vincent; Mocroft, Amanda; Rockstroh, Juergen

    2008-01-01

    BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV...... for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4...

  4. FGFR2 protein expression in breast cancer: nuclear localisation and correlation with patient genotype

    Directory of Open Access Journals (Sweden)

    Thompson Alastair M

    2011-03-01

    Full Text Available Abstract Background Single Nucleotide Polymorphisms (SNPs in intron 2 of the Fibroblast Growth Factor Receptor Type 2 (FGFR2 gene, including rs2981582, contribute to multifactorial breast cancer susceptibility. The high risk polymorphism haplotype in the FGFR2 gene has been associated with increased mRNA transcription and altered transcription factor binding but the effect on FGFR2 protein expression is unknown. 40 breast tumours were identified from individuals with known rs2981582 genotype. Tumour sections were stained for FGFR2 protein expression, and scored for nuclear and cytoplasmic staining in tumour and surrounding normal tissue. Findings FGFR2 immunohistochemistry demonstrated variable nuclear staining in normal tissue and tumour tissue, as well as consistent cytoplasmic staining. We did not find an association between nuclear staining for FGFR2 and genotype, and there was no association between FGFR2 staining and estrogen or progestogen receptor status. There was an association between presence of nuclear staining for FGFR2 in normal tissue and presence of nuclear staining in the adjacent tumour (Fishers exact test, p = 0.002. Conclusions Variable nuclear staining for FGFR2 in breast cancer, but an absence of correlation with rs2981582 genotype suggests that the mechanism of action of polymorphisms at the FGFR2 locus may be more complex than a direct effect on mRNA expression levels in the final cancer. The effect may relate to FGFR2 function or localisation during breast development or tumourigenesis. Nuclear localisation of FGFR2 suggests an important additional role for this protein in breast development and breast cancer, in addition to its function as a classical cell surface receptor.

  5. The Predictive Value of On-treatment Virological Response for Sustained Virological Response in Patients with Chronic Hepatitis C Receiving a Personalized Treatment Program

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Objective To investigate the effects of individualised treatment with peginterferon alpha-2a (40 kD) plus ribavirin in Chinese patients with CHC. Methods Total of 297 consecutive Chinese patients were enrolled, including 250 na?ve cases and 47 cases who were previously treated. Treatment duration was determined according to viral genotypes, prior treatment history and viral responses at week 4, 12 and 24. Results Totally, 235 patients (79.1%) completed treatment and 186 (87.3%) achieved SVR. And 219 out of 289 (75.8%) patients achieved HCV RNA negative at week 4 (RVR) and 259 of 276 (93.8%) at week 12. Among the 164 patients with RVR who completed follow-up, 158 (96.3%) achieved SVR. Patients with RVR had lower baseline viral loads than patients without RVR (P=0.034). The positive predictive value (PPV) of RVR for SVR was 90.7%(OR 2.10 vs. non-RVR, 95%CI:0.50-8.7). Similar outcomes were observed among patients with HCV undetectable at week 12. Conclusions Viral suppression by week 4 is associated with a high rate of treatment success in treatment na?ve and experienced patients receiving individualized CHC therapy.

  6. Distribution of genotypes C825T polymorphism G-protein β3-subunit gene in patients with hypertension depending on body mass index

    Directory of Open Access Journals (Sweden)

    Prystupa L.N.

    2015-09-01

    Full Text Available The aim of the study was to investigate the frequency of genotypes of C825T polymorphism G-protein β3-subunit gene (GNB3 in patients with arterial hypertension (AH, depending on body mass index (BMI. The study involved 155 patients with verified diagnosis of AH (study group and 50 healthy individuals (control group. The patients of the main group were divided into 3 groups according to BMI: I - 35 patients with normal body weight, II - 38 patients with overweight, III - 82 patients with obesity. We used general clinical, anthropometric, instrumental, molecular-genetic and statistical methods. Probability of differences in the frequency of alleles and genotypes was determined using χ² criteria. Pairwise comparison of groups was made using nonparametric Mann-Whitney test. The difference was considered statistically significant at p <0,05. Investigation of the distribution of genotypes C825T polymorphism GNB3 in patients with AH according to BMI showed statistically significant increase in the frequency of genotypes C / T and T / T and T allele in patients with overweight and obesity as compared with patients with normal body weight (χ² = 26 8; p <0.001. The risk of weight increase in AH patients with T allele carriers is 2,2 times higher than in C allele carriers. Association of C825T polymorphism of GNB3 with a tendency to obesity and overweight in patients with AH was proved.

  7. Predictability of IL-28B-polymorphism on protease-inhibitor-based triple-therapy in chronic HCV-genotype-1 patients: A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Nicolae-Catalin; Mechie; Christian; Rver; Silke; Cameron; Ahmad; Amanzada

    2014-01-01

    AIM: To investigate the predictability of interleukin-28 B single nucleotide polymorphism rs12979860 with respect to sustained virological response(SVR) in chronically hepatitis C virus(HCV) genotype-1 patients treated with a protease-inhibitor and pegylated interferon-α(Peg-INF-α) based triple-therapy. METHODS: We searched PubMed, the Cochrane Library and Web of Knowledge for studies regarding the interleukin 28B(IL-28B)-genotype and protease-inhibitor based triple-therapy. Ten studies with 2707 patients were included into this meta-analysis. We used regression methods in order to investigate determinants of SVR.RESULTS: IL-28B-CC-genotype patients achieved higher SVR rates(odds 5.34, 95%CI: 3.81-7.49) than IL-28B-non-CC-genotype patients(1.88, 95%CI: 1.43-2.48) receiving triple-therapy. The line of therapy(treatment-nave or-experienced for Peg-INF-α) did not affect the predictive value of IL-28B(P = 0.1). IL-28BCC-genotype patients treated with protease inhibitorbased triple-therapy consisting of Boceprevir, Simeprevir, Telaprevir or Vaniprevir showed odds of 3.38, 14.66, 7.84 and 2.91, respectively. The odds for CC genotype patients treated with Faldaprevir cannot be quantified, as only a single study with a 100% SVR rate was available.CONCLUSION: IL-28B-SNP predicts the outcome for chronic HCV genotype-1 patients receiving protease inhibitor-based triple-therapy. The predictive value varies between the different protease inhibitors.

  8. Changing prevalent T serotypes and emm genotypes of Streptococcus pyogenes isolates from streptococcal toxic shock-like syndrome (TSLS) patients in Japan.

    Science.gov (United States)

    Ikebe, T; Murai, N; Endo, M; Okuno, R; Murayama, S; Saitoh, K; Yamai, S; Suzuki, R; Isobe, J; Tanaka, D; Katsukawa, C; Tamaru, A; Katayama, A; Fujinaga, Y; Hoashi, K; Ishikawa, J; Watanabe, H

    2003-06-01

    We surveyed T serotypes and emm genotypes of Streptococcus pyogenes isolates from streptococcal toxic shock-like syndrome (TSLS) patients. T1 (emm1) remained dominant through 1992 to 2000, but the dominant T3 (emm3.1) strains from 1992 to 1995 disappeared during 1996-2000. Strains of several emm genotypes emerged during 1996-2000, indicating alterations in the prevalent strains causing TSLS.

  9. Value of preemptive CYP2C19 genotyping in allogeneic stem cell transplant patients considered for pentamidine administration.

    Science.gov (United States)

    Afrin, Lawrence B; Afrin, Jessica B

    2011-01-01

    Pneumocystis jirovecii prophylaxis is standard in allogeneic stem cell transplantation (alloSCT), sometimes with pentamidine at a low dose inhaled monthly. Human metabolism of pentamidine depends on cytochrome P450 2C19 (CYP2C19). The frequency of mutant CYP2C19 forms with decreased function (from 2% of Caucasians to 30% of Asians and 79% of certain Polynesians), together with common use of CYP2C19 inhibitors in the alloSCT process, creates risk for impaired pentamidine clearance resulting in toxicity ordinarily expected only with high doses given for active infection. We examined the charts of 32 consecutive pentamidine-prophylaxed alloSCT patients at our center. We assessed hospital charges for the management of toxicities unexplained at the time but likely attributable, in retrospect, to pentamidine. Twenty-eight percent experienced significant toxicities (incurring added charges of at least US$5000). Thirteen percent suffered major toxicity (incurring added charges of at least US$25, 000; median added charge $351, 701) and shorter survival (326 vs. 622 d for all pentamidine recipients), including 6% who died of pentamidine toxicities [one proven postmortem to have a (non-functional) homozygous CYP2C19*2 mutation]. Charges for care attributable to pentamidine toxicity exceeded what preemptive genotyping would have cost by 73-fold. These findings encourage routine use of preemptive CYP2C19 genotyping in alloSCT patients considered for pentamidine.

  10. Social Cognition in Williams Syndrome: Genotype/phenotype Insights from Partial Deletion Patients

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    Annette eKarmiloff-Smith

    2012-05-01

    Full Text Available Identifying genotype-phenotype relations in human social cognition has been enhanced by the study of Williams syndrome (WS. Indeed, individuals with WS present with a particularly strong social drive, and researchers have sought to link deleted genes in the WS Critical Region (WSCR of chromosome 7q11.23 to this unusual social profile. In this paper, we provide details of two case studies of children with partial genetic deletions in the WSCR: an 11-year-old female with a deletion of 24 of the 28 WS genes, and a 14-year-old male who presents with the opposite profile, i.e. the deletion of only 4 genes at the telomeric end of the WSCR. We tested these two children on a large battery of standardised and experimental social perception and social cognition tasks - both implicit and explicit - as well as standardised social questionnaires and general psychometric measures. Our findings reveal a partial WS socio-cognitive profile in the female, contrasted with a more autistic-like profile in the male. We discuss the implications of these findings for genotype/phenotype relations, as well as the advantages and limitations of animal models and of case study approaches.

  11. Vitamin D improves viral response in hepatitis C genotype 2-3 na(i)ve patients

    Institute of Scientific and Technical Information of China (English)

    Assy Nimer; Abu Mouch

    2012-01-01

    AIM:To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3.METttODS:Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups:Treatment group [20 subjects,age 48 ± 14 years,body mass index (BMI) 30 ± 6,65% male],who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV),together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d,10 drops/d,normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects,age 45 ± 10 years,BMI 26 ± 3,60% male),who received identical therapy without vitamin D.HCV RNA was assessed by reverse transcription polymerase chain reaction.Undetectable HCV RNA at 4,12 and 24 wk after treatment was considered as rapid virological response,complete early virological response,and sustained virological response (SVR),respectively.Biomarkers of inflammation were measured.RESULTS:The treatment group with vitamin D had higher BMI (30±6 vs 26 ± 3,P < 0.02),and high viral load (> 400 000 IU/mL,65% vs 40%,P < 0.01)than controls.Ninety-five percent of treated patients were HCV RNA negative at week 4 and 12.At 24 wk after treatment (SVR),19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001).Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment,to a mean level of (34 ± 11 ng/mL).Logistic regression analysis identified vitamin D supplement [odds ratio (OR) 3.0,95% CI 2.0-4.9,P <0.001],serum vitamin D levels (< 15 or > 15 ng/mL,OR 2.2,P < 0.01),and BMI (< 30 or > 30,OR 2.6,P < 0.01) as independent predictors of viral response.Adverse events were mild and typical of Peg/RBV.CONCLUSION:Low vitamin D levels predicts negative treatment outcome,and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 significantly improves viral response.

  12. Querying phenotype-genotype relationships on patient datasets using semantic web technology: the example of Cerebrotendinous xanthomatosis.

    Science.gov (United States)

    Taboada, María; Martínez, Diego; Pilo, Belén; Jiménez-Escrig, Adriano; Robinson, Peter N; Sobrido, María J

    2012-07-31

    Semantic Web technology can considerably catalyze translational genetics and genomics research in medicine, where the interchange of information between basic research and clinical levels becomes crucial. This exchange involves mapping abstract phenotype descriptions from research resources, such as knowledge databases and catalogs, to unstructured datasets produced through experimental methods and clinical practice. This is especially true for the construction of mutation databases. This paper presents a way of harmonizing abstract phenotype descriptions with patient data from clinical practice, and querying this dataset about relationships between phenotypes and genetic variants, at different levels of abstraction. Due to the current availability of ontological and terminological resources that have already reached some consensus in biomedicine, a reuse-based ontology engineering approach was followed. The proposed approach uses the Ontology Web Language (OWL) to represent the phenotype ontology and the patient model, the Semantic Web Rule Language (SWRL) to bridge the gap between phenotype descriptions and clinical data, and the Semantic Query Web Rule Language (SQWRL) to query relevant phenotype-genotype bidirectional relationships. The work tests the use of semantic web technology in the biomedical research domain named cerebrotendinous xanthomatosis (CTX), using a real dataset and ontologies. A framework to query relevant phenotype-genotype bidirectional relationships is provided. Phenotype descriptions and patient data were harmonized by defining 28 Horn-like rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were designed following the initial list of competency questions. As the approach is based on OWL, the semantic of the framework adapts the standard logical model of an open world assumption. This work demonstrates how semantic web technologies can be used to support flexible representation and computational inference mechanisms

  13. Improved Prediction of Endoxifen Metabolism by CYP2D6 Genotype in Breast Cancer Patients Treated with Tamoxifen

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    Werner Schroth

    2017-08-01

    Full Text Available Purpose: Prediction of impaired tamoxifen (TAM to endoxifen metabolism may be relevant to improve breast cancer treatment, e.g., via TAM dose increase. The polymorphic cytochrome P450 2D6 (CYP2D6 strongly determines an individual’s capacity for endoxifen formation, however, CYP2D6 phenotype assignments inferred from genotype widely differ between studies. Thus, we modeled plasma endoxifen predictability depending on variable CYP2D6 genotype groupings.Methods: CYP2D6 diplotype and metabolite plasma concentrations were assessed in 908 pre- and post-menopausal estrogen receptor (ER-positive, TAM treated early breast cancer patients of Caucasian (N = 678, Middle-Eastern Arab (N = 77, and Asian (N = 153 origin. Robust coefficients of determination (R2 were estimated for endoxifen (E or metabolic ratio endoxifen/desmethyl-TAM (E/DMT as dependent and different CYP2D6 phenotype assignments as independent variables. Allele activity scores (ASs were modified with respect to a reduced ∗10 allele activity. Predictability of endoxifen plasma concentrations above the clinical threshold of 5.9 ng/mL was investigated by receiver operating characteristic (ROC analysis.Results: CYP2D6 diplotypes (N = 898 were strongly associated with E and E/DMT independent of age (P < 10-15. Across all ethnicities, 68–82% inter-patient variability of E/DMT was explained by CYP2D6 diplotype, while plasma endoxifen was predictable by 39–58%. The previously used codeine specific phenotype classification showed worse prediction for both endpoints particularly in Asians (median R2< 20%; P < 10-9. Downgrading of ∗10 activity slightly improved the explanatory value of metabolizer phenotype (P < 0.002. Endoxifen plasma concentrations above the clinical threshold of 5.9 ng/mL were achieved in 82.3% of patients and were predictable (96% sensitivity, 57% specificity by CYP2D6 diplotypes with AS > 0.5, i.e., omitting PM/PM and PM/IM patients.Conclusion: The CYP2D6 explanatory

  14. Querying phenotype-genotype relationships on patient datasets using semantic web technology: the example of cerebrotendinous xanthomatosis

    Directory of Open Access Journals (Sweden)

    Taboada María

    2012-07-01

    Full Text Available Abstract Background Semantic Web technology can considerably catalyze translational genetics and genomics research in medicine, where the interchange of information between basic research and clinical levels becomes crucial. This exchange involves mapping abstract phenotype descriptions from research resources, such as knowledge databases and catalogs, to unstructured datasets produced through experimental methods and clinical practice. This is especially true for the construction of mutation databases. This paper presents a way of harmonizing abstract phenotype descriptions with patient data from clinical practice, and querying this dataset about relationships between phenotypes and genetic variants, at different levels of abstraction. Methods Due to the current availability of ontological and terminological resources that have already reached some consensus in biomedicine, a reuse-based ontology engineering approach was followed. The proposed approach uses the Ontology Web Language (OWL to represent the phenotype ontology and the patient model, the Semantic Web Rule Language (SWRL to bridge the gap between phenotype descriptions and clinical data, and the Semantic Query Web Rule Language (SQWRL to query relevant phenotype-genotype bidirectional relationships. The work tests the use of semantic web technology in the biomedical research domain named cerebrotendinous xanthomatosis (CTX, using a real dataset and ontologies. Results A framework to query relevant phenotype-genotype bidirectional relationships is provided. Phenotype descriptions and patient data were harmonized by defining 28 Horn-like rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were designed following the initial list of competency questions. As the approach is based on OWL, the semantic of the framework adapts the standard logical model of an open world assumption. Conclusions This work demonstrates how semantic web technologies can be used to support

  15. NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain

    Science.gov (United States)

    Jimenez-Sousa, María Ángeles; Gutiérrez-Rivas, Mónica; Álvaro-Meca, Alejandro; García-Álvarez, Mónica; Harrigan, P. Richard; Fedele, Cesare Giovanni; Briz, Verónica

    2016-01-01

    Background Resistance-associated variants have been related to treatment failure of hepatitis C virus (HCV) therapy with direct-acting antiviral drugs. The aim of our study was to analyze the prevalence of clinically relevant resistance-associated variants within NS3 in patients infected with HCV genotype 1a (GT1a) in Spain. Methods We performed a cross-sectional study on 2568 patients from 115 hospitals throughout Spain (2014–2015). The viral NS3 protease gene was amplified by nested polymerase chain reaction and sequenced by Sanger sequencing using an ABI PRISM 377 DNA sequencer. Additionally, clade information for genotype 1a was obtained by using the software geno2pheno (http://hcv.geno2pheno.org/). Results In total, 875 out of 2568 samples were from human immunodeficiency virus (HIV)/HCV-coinfected patients. Q80K was the main RAV found in our patients (11.1%) and the rest of the resistance-associated variants had a lower frequency, including S122G (6.23%), T54S (3.47%), V55A (2.61%), and V55I (2.15%), which were among the most frequent after Q80K. Overall, 286 samples had the Q80K polymorphism (11.1%) and 614 (23.9%) were GT1a clade I. HIV/HCV-coinfected patients had a higher frequency of Q80K and GT1a clade I than HCV-monoinfected patients (12.9% vs. 9.6% [p = 0.012] and 28.5% vs. 21.4% [p<0.001], respectively). Both the prevalence of Q80K and GT1a clade I were not uniform throughout the country (p<0.001), which ranged from 7.3%-22.2% and 15.7%-42.5%, respectively. The frequency of the Q80K polymorphism was far higher in patients infected with GT1a clade I than in patients infected with GT1a clade II (41.5% vs. 1.6%; p<0.001). Conclusions The prevalence of most resistance-associated variants in NS3 was low in patients infected with HCV GT1a in Spain, except for Q80K (11.1%), which was also notably higher in HIV/HCV-coinfected patients. The vast majority of Q80K polymorphisms were detected in GT1a clade I. PMID:27685471

  16. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations

    Science.gov (United States)

    Boylan, Brian; Rice, Anne S.; De Staercke, Christine; Eyster, M. Elaine; Yaish, Hassan M.; Knoll, Christine M.; Bean, Christopher J.; Miller, Connie H.

    2015-01-01

    Summary Background Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand Factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA, and pose a potential for misdiagnosis. Objectives Investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities, and VWF genotypes. Patients/Methods Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, patient's VWF capacity to bind FVIII (VWF:FVIIIB), and VWF sequence. Results Four cases had VWF:Ag <3 IU/dL and VWF mutations consistent with Type3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type1 VWD (VWD1) (n=5 cases and 1 control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n=1 case). One control had VWF:Ag <30 IU/dl, and seven patients (4 cases and 3 controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. Conclusions These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy. PMID:25780857

  17. the rtA181 Mutation Produces Similar Clinical and Cellular Characteristics in Patients infected with Hepatitis B Virus Genotypes B and C

    Institute of Scientific and Technical Information of China (English)

    Ping Li; Xi Xiong; Xin Zhang; Zhi-guo Yang; Lei Gao; Mao-rong Wang

    2014-01-01

    Objective To investigate the association between HBV genotypes and characteristics of rtA181 mutation. Methods Total of 85 chronic hepatitis B (CHB) patients who appeared rtA181 mutation after nucleos(t)ide analogs (NAs) therapy were enrolled in this study. Levels of serum ALT, AST, HBV DNA and HBsAg titers were monitored during therapy. HBV reverse transcriptase genes were amplified and sequenced to identify genotypes and resistance mutations. Virions and HBsAg in HepG2 cell with rtA181 mutation were also compared between genotypes B and C. Results The majority of sera contained HBV genotypes B (15.7%) and C (84.3%). There were no significant difference of rtA181 mutant patterns between genotypes (P> 0.05). After emergence of rtA181 mutation, serum ALT, AST, HBV DNA levels and HBsAg titers were decreased than that at baseline (P0.05). In cellular experiment, there were no significant differences between genotypes B and C not only in HBV virions but also in HBsAg titres (P>0.05). Conclusions No differences of clinical characteristics and cellular results were found in rtA181 mutation of HBV genotypes B and C.

  18. Ribavirin rather than PEG-interferon pharmacodynamics predict nonresponse to antiviral therapy in naive chronic hepatitis C patients.

    NARCIS (Netherlands)

    Vlerken, L.G. Van; Huisman, E.J.; Soest, H. van; Boland, G.J.; Drenth, J.P.H.; Siersema, P.D.; Burger, D.M.; Erpecum, K.J. van

    2012-01-01

    Twenty to fifty per cent of patients with chronic hepatitis C (CHC) experience nonresponse to current antiviral therapy, which may relate in part to ribavirin or PEG-interferon pharmacodynamics. We evaluated potential relevance of various factors for nonresponse. Two hundred forty-two naive CHC pati

  19. Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients.

    Science.gov (United States)

    Zumárraga, Mercedes; Dávila, Ricardo; Basterreche, Nieves; Arrue, Aurora; Goienetxea, Biotza; Zamalloa, María I; Erkoreka, Leire; Bustamante, Sonia; Inchausti, Lucía; González-Torres, Miguel A; Guimón, José

    2010-01-01

    Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.

  20. Prevalence of human papillomavirus and its genotype among 1336 invasive cervical cancer patients in Hunan province, central south China.

    Science.gov (United States)

    Wang, Linqian; Wu, Baiping; Li, Junjun; Chen, Liyu

    2015-03-01

    Existing data on the genotype distribution of human papillomavirus (HPV) are limited in Hunan province, central south China. To evaluate the prevalence of HPV infection and its genotype among women with invasive cervical cancer in Hunan, a total of 1,336 patients were included in this study between July 2012 and June 2013. Eighteen high-risk and eight low-risk genotypes of HPV were detected by Luminex xMAP technology. The results show that HPV prevalence in invasive cervical cancer in Hunan was 75.7%. A single HPV infection was found in 82.3% of the HPV-positive samples, and 91.8% of the cases had high-risk HPV infection. The most common HPV type was HPV 16 (50.6%), followed by HPV 58 (12.4%), HPV 52 (10.9%), HPV 18 (7.3%), HPV 33 (5.5%), HPV 59 (4.2%), HPV 39 (4.0%), HPV 61 (3.4%), HPV 31 (3.3%), and HPV 56 (3.2%). A single infection with HPV 16 was detected in 42.5% of the samples, which was significantly more frequent than any other HPV type in this population. Dual-infection with HPV 16 and HPV 52 were relatively common. The available vaccines for HPV 16 and 18 are therefore expected to have a substantial impact on reducing the burden of cervical cancer in China, even though HPV 18 showed a lower frequency. In addition to HPV 16 and 18, other HPV types including 58, 52, and 33, should be targeted in the next generation HPV vaccines.

  1. Prevalence of HFE mutations and relation to serum iron status in patients with chronic hepatitis C and patients with nonalcoholic fatty liver disease in Taiwan

    Institute of Scientific and Technical Information of China (English)

    Tsung-Jung Lin; Chih-Lin Lin; Chaur-Shine Wang; Shu-O Liu; Li-Ying Liao

    2005-01-01

    AIM: To assess the prevalence of the two mutations, C282Y and H63D of HFE gene, in healthy subjects, patients with chronic hepatitis C (CHC), and patients with nonalcoholic fatty liver disease (NAFLD) in Taiwan and to explore the contribution of the HFE mutation on serum iron stores in CHC and NAFLD groups.METHODS: We examined C282Y and H63D mutations of HFE gene in 125 healthy subjects, 29 patients with CHC,and 33 patients with NAFLD. The serum iron markers,including ferritin, iron, and total iron binding capacity (TIBC),were assessed in all patients.RESULTS: All of the healthy subjects and patients were free from C282Y mutation. The prevalence of H63D heterozygosity was 4/125 (3.20%) in healthy subjects, 2/29(6.90%) in CHC group, and 1/33 (3.03%) in NAFLD group.The healthy subjects showed no significant difference in the prevalence of H63D mutation as compared with the CHC or NAFLD group. Increased serum iron store was found in 34.48% of CHC patients and 36.36% of NAFLD patients.In three patients of H63D heterozygosity, only one CHC patient had increased serum iron store. There was no significant difference in the prevalence of HFE mutations between patients with increased serum iron store and those without in CHC or NAFLD group.CONCLUSION: The HFE mutations may not contribute to iron accumulation in the CHC or NAFLD group even when serum iron overload is observed in more than one-third of these patients in Taiwan.

  2. Diltiazem augments the influence of MDR1 genotype status on cyclosporine concentration in Chinese patients with renal transplantation.

    Science.gov (United States)

    Wang, Yi-xi; Li, Jia-li; Wang, Xue-ding; Zhang, Yu; Wang, Chang-xi; Huang, Min

    2015-07-01

    Co-administration of diltiazem can reduce the dosage of cyclosporine (CsA) in patients with renal transplantation. In this study, we investigated how diltiazem altered the relationship between MDR1 genetic polymorphisms and CsA concentration in Chinese patients with renal transplantation. A total of 126 renal transplant patients were enrolled. All the patients received CsA (2-4 mg·kg(-1)·d(-1)), and diltiazem (90 mg/d) was co-administered to 76 patients. MDR1-C1236T, G2677T/A, and C3435T polymorphisms were genotyped. The whole blood concentration was measured using the FPIA method, and the adjusted trough concentrations were compared among the groups with different genotypes. In all patients, MDR1-C1236T did not influence the adjusted CsA trough concentration. With regard to MDR1-3435, the adjusted CsA trough concentration was significantly higher in TT carriers than in CC and CT carriers when diltiazam was co-administered (58.83±13.95 versus 46.14±7.55 and 45.18±12.35 ng/mL per mg/kg, P=0.011), and the differences were not observed in patients without diltiazam co-administered. With regard to MDR1-2677, the adjusted CsA trough concentration was significantly higher in TT carriers than in GG and GT carriers when diltiazam was co-administered (61.31±12.93 versus 52.25±7.83 and 39.70±7.26 ng/mL per mg/kg, P=0.0001). The differences were also observed in patients without diltiazam co-administered (43.27±5.95 versus 35.22±7.55 and 29.54±5.35 ng/mL per mg/kg, P=0.001). The adjusted CsA trough blood concentration was significantly higher in haplotype T-T-T and haplotype T-T-C carriers than in non-carriers, regardless of diltiazem co-administered. MDR1 variants influence the adjusted CsA trough concentration in Chinese patients with renal transplant, and the influence more prominent when diltiazem is co-administered.

  3. Cost-effectiveness analysis of HLA-B5801 genotyping in the treatment of gout patients with chronic renal insufficiency in Korea.

    Science.gov (United States)

    Park, Dong-Jin; Kang, Ji-Hyoun; Lee, Jeong-Won; Lee, Kyung-Eun; Wen, Lihui; Kim, Tae-Jong; Park, Yong-Wook; Park, Sung-Hwan; Lee, Shin-Seok

    2015-02-01

    Allopurinol-induced severe cutaneous adverse reactions (SCARs) are relatively rare but cause high rates of morbidity and mortality. Studies have shown that the HLA-B5801 allele and renal impairment are strongly associated with SCARs. Recent American College of Rheumatology guidelines recommend that, prior to treatment with allopurinol, the HLA-B5801 genotype of gout patients at high risk for SCARs, including Korean patients with chronic renal insufficiency, should be determined. However, whether such genotyping is cost-effective is unknown. This study evaluated the cost-effectiveness of HLA-B5801 genotyping for the treatment of gout in patients with chronic renal insufficiency in Korea. A decision analytical model over a time period of 12 months was employed to compare the cost and outcomes of treatment informed by HLA-B5801 genotyping with that of a conventional treatment strategy using a hypothetical cohort of gout patients with chronic renal insufficiency. Direct medical costs were obtained from real patients with SCARs from 2 tertiary hospitals. Outcomes were measured as a total expected cost and an incremental cost-effectiveness ratio. In the base model, the total expected cost and probability of continuation of gout treatment without SCARs for the conventional and HLA-B5801 screening strategies were $1,193 and 97.8% and $1,055 and 100%, respectively. The results were robust according to sensitivity analyses. Our model suggests that gout treatment informed by HLA-B5801 genotyping is less costly and more effective than treatment without genotyping, and HLA-B5801 genotyping could considerably reduce the occurrence of allopurinol-induced SCARs and related deaths. Copyright © 2015 by the American College of Rheumatology.

  4. Association of ATP-Binding Cassette Transporter (ABC) Gene Polymorphisms with Viral Load in Patients with Genotype 1 Hepatitis C Virus Infection.

    Science.gov (United States)

    Chen, Long; Rao, Huiying; Zhang, Wei; Liu, Feng; Jiang, Dong; Wei, Lai

    2016-09-01

    ATP-binding cassette transporters (ABC) gene polymorphisms are associated with various biological functions, including hepatitis C virus (HCV) infection. This study aims to explore the impact of ABC transporters polymorphisms on HCV viral load in chronic treatment-naïve hepatitis C patients. We recruited 347 Chinese Han patients chronically infected with genotype 1 HCV in this study. Ten single nucleotide polymorphism (SNPs) in ABCA1, ABCB5, ABCB11, ABCG2, ABCG5, ABCG10 were analyzed by custom chip from Illumina. Allele frequency analysis and genotype frequency analysis were performed. Patients were categorized according to pretreatment HCV viral load (VL) with a cutoff level 600 000 IU/mL. No significant variations on gender and age were observed in the two groups. G allele of rs3890182 and C allele of rs1883025 in ABCA1 gene were significantly associated with lower HCV viral load (p = 0.013 and p = 0.006) in allele frequency analysis. GG genotype of rs3890182 and CC genotype of rs1883025 in ABCA1 gene were significantly associated with lower HCV viral load (p = 0.027 and p = 0.013) in genotype frequency analysis. Quantitative analysis showed significantly lower viral load in patients with CC genotype of rs1883025 (p = 0.012). Allele associated lower HCV viral load was reported to be associated with higher HDL cholesterol level. Our finding suggests that ABCA1 gene polymorphism in rs1883025 is significantly associated with HCV VL in patients infected with HCV genotype 1.

  5. Comparison and significance of specific and non-specific cellular immunity in patients with chronic hepatitis B caused by infection with genotypes B or C of hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The present study was designed to investigate possible relationships between the genotypes of hepatitis B virus(HBV) and the HBV-specific cytotoxic T lymphocyte(CTL) responses.HBV genotypes,HBV specific CTL HBV DNA and other markers of HBV infection were determined in 138 patients with chronic hepatitis B.The results showed that the patients infected with genotype C(n=62) had a significantly lower HBV-specific CTL response than those who were infected with HBV genotype B(P<0.01).HBV DNA titer was higher in patients infected with HBV genotype C than in those infected with HBV geno-type B(P<0.01).Both alanine aminotransferase(ALT) and total bilirubin(TBIL) were higher in HBV genotype C infected patients than in those infected with genotype B(P<0.01 and <0.05,respectively).These results suggest that compared with CHB patients infected with HBV genotype B,the higher HBV DNA level and more severe liver damages in the patients infected with genotype C of HBV may be associated with genotype C of the virus.

  6. Molecular epidemiological analysis of Saffold cardiovirus genotype 3 from upper respiratory infection patients in Taiwan.

    Science.gov (United States)

    Lin, Tsuey-Li; Lin, Ting-Han; Chiu, Shu-Chun; Huang, Yuan-Pin; Ho, Cheng-Mao; Lee, Chia-Chi; Wu, Ho-Sheng; Lin, Jih-Hui

    2015-09-01

    Saffold cardiovirus (SAFV) belongs to the Cardiovirus genus of Picornaviridae family, and may be a relevant new human pathogen; Thus far, eleven genotypes have been identified. The SAFV type 3 (SAFV-3) is thought to be the major genotype and is detected relatively frequently in children with acute gastroenteritis and respiratory illness. The epidemiology and pathogenicity of SAFV-3 remain unclear. To investigate the genomic and epidemiologic profiles of SAFV-3 infection in Taiwan. Virus was detected in respiratory samples from children suffering for URI. SAFV-3 isolates were detected by isolation on cell culture and IF assay. The molecular typing was performed by RT-PCR and was sequenced to compare with reference strains available in the NCBI GeneBank. Serum samples were collected from 2005 to 2013 in Taiwan for seroprevalence investigation. A total of 226 specimens collected from children with URIs, 22 (9.73%) were positive for SAFV-3. The majority of SAFV-3 infections were found in children less than 6 years of age (14 of 22, 63.6%). Genetic analysis of VP1 coding region of Taiwanese isolates shown an 83.2-97.7% difference from other available SAFV-3 sequences in NCBI GenBank. Phylogenetic analysis revealed there is three genetic groups of SAFV-3 co-circulated in Taiwan during the study period. In addition, seroprevalence investigation results indicated that SAFV-3 infection occurs early in life and 43.7-77.8% of children aged between 6 months to 9 years old, had neutralizing antibodies against SAFV-3. SAFV-3 may have circulated in Taiwan for some time and it appears to be one of the etiological agents responsible for URIs in children. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Impact of Body Weight Reduction via Diet and Exercise on the Anti-Viral Effects of Pegylated Interferon Plus Ribavirin in Chronic Hepatitis C Patients with Insulin Resistance: A Randomized Controlled Pilot Trial.

    Science.gov (United States)

    Iwane, Shinji; Mizuta, Toshihiko; Kawaguchi, Yasunori; Takahashi, Hirokazu; Oza, Noriko; Oeda, Satoshi; Nakashita, Shunya; Kuwashiro, Takuya; Otsuka, Taiga; Kawazoe, Seiji; Eguchi, Yuichiro; Anzai, Keizo; Ozaki, Iwata; Fujimoto, Kazuma

    2015-01-01

    Insulin resistance (IR) modifies the anti-viral effects of interferon (IFN) therapy in patients with chronic hepatitis C (CHC). This prospective study evaluated whether lifestyle interventions improve the anti-viral response to treatment with pegylated (PEG)-IFN plus ribavirin (RBV) in patients with CHC. The study cohort consisted of 60 patients chronically infected with a high viral load of hepatitis C virus genotype 1b and a homeostasis model assessment of IR (HOMA-IR) value above 2. The patients were divided into two groups, an intervention group (n=26) and a control group (n=34). The patients in the intervention group were prescribed diet and exercise treatment for 3-6 months to reduce their body weight by ≥5% before starting treatment with PEG-IFN plus RBV. Diet and exercise significantly reduced the HOMA-IR values in the intervention group, from 3.4 to 2.5 (p=0.0009), especially among the 15 patients who achieved a body weight reduction of ≥5%. The viral disappearance rate at 12 weeks was significantly higher in the intervention group among the patients with a ≥5% weight reduction than in the control group (53.3% vs. 23.5%, p=0.01). However, the sustained viral response (SVR) rates were similar. Improvements in IR achieved through weight reduction via lifestyle interventions may enhance the early viral response to PEG-IFN plus RBV in patients with CHC. However, this intervention program has no effect on the SVR rate.

  8. Robust full-length hepatitis C virus genotype 2a and 2b infectious cultures using mutations identified by a systematic approach applicable to patient strains

    DEFF Research Database (Denmark)

    Li, Yi-Ping; Ramirez, Santseharay; Gottwein, Judith M;

    2012-01-01

    Hepatitis C virus (HCV) infection is a leading cause of chronic liver diseases worldwide, but treatment options are limited. Basic HCV research required for vaccine and drug development has been hampered by inability to culture patient isolates, and to date only the JFH1 (genotype 2a) recombinant...... replicates spontaneously in hepatoma cells and releases infectious virus. A JFH1 chimera with the 5' end through NS2 from another genotype 2a strain, J6, had enhanced infectivity. However, the full-length J6 clone (J6CF), which we previously found to be fully functional in vivo, was replication incompetent...... of the genetically divergent isolate J8 (genotype 2b), which differed from the J6 nucleotide sequence by 24%. The most efficient recombinant, J8cc, had nine adaptive mutations and was genetically stable after viral passage. The availability of these robust JFH1-independent genotype 2a and 2b culture systems...

  9. First baseline of circulating genotypic lineages of Mycobacterium tuberculosis in patients from the brazilian borders with Argentina and Paraguay.

    Science.gov (United States)

    Machado, Luzia Neri C; Marcondes, Nadir R; Leite, Clarice Q Fijimura; Santos, Adolfo C Barreto; Pavan, Fernando Rogério; Baldin, Vanessa Pietrowski; Castilho, Aline Lemes; Siqueira, Vera Lúcia D; Baeza, Lilian Cristiane; Berghs, Henri; Cardoso, Rosilene Fressatti

    2014-01-01

    At the triple border Brazil/Paraguay/Argentina there is easy mobility from one city to another for economic and tourism activities. This constant and fast population mobility is mainly to visit Iguazu Falls, in the Iguazu River, on the border of the Brazilian state of Paraná and the Argentina. As the incidence of tuberculosis is high in this setting, our study aimed to establish a first baseline of circulating genotypic lineages of Mycobacterium tuberculosis. This study included 120 patients from 10 cities in southwestern Paraná, Brazil with pulmonary symptoms, from July 2009 to July 2011. Information about sex, age, clinical features and address was collected by reviewing the national tuberculosis notification database. Of these, 96 (80%) isolates were identified as M. tuberculosis and 22 (22.9%) were drug resistant (20, 20.8% INH mono-resistant and 2, 2.1% multidrug-resistant). All isolates were subjected to genotyping by Spoligotyping and MIRU-VNTR typing. The distribution of the isolates analyzed by spoligotyping revealed 30 distinct patterns. The four mainly detected clades were Latin American and Mediterranean (LAM), ill-defined T, Haarlem (H) and S. The MIRU-VNTR showed 85 distinct patterns. Spoligotyping combined to MIRU-VNTR allowed 90 distinct patterns. Our study demonstrated that there is significant molecular diversity in circulating M. tuberculosis, with predominance of the LAM and T clades in cities of southwestern Paraná, Brazil, bordering Argentina and Paraguay.

  10. Variations in the core promoter/pre-core region in HBV genotype C in Japanese and Northern Vietnamese patients.

    Science.gov (United States)

    Truong, Bui Xuan; Yano, Yoshihiko; Seo, Yasushi; Phuong, Tran Minh; Tanaka, Yasuhito; Kato, Hirotaka; Miki, Akira; Utsumi, Takako; Azuma, Takeshi; Trach, Nguyen Khanh; Mizokami, Masashi; Hayashi, Yoshitake; Kasuga, Masato

    2007-09-01

    Hepatitis B virus (HBV) subgenotypes Cs (C1) and Ce (C2) are common in East Asia. To investigate the genomic difference of HBV genotype C between two separated regions, 50 subgenotype Cs-infected Vietnamese and 70 subgenotype Ce-infected Japanese patients were enrolled for analysis. The patients were categorized to either a hepatocellular carcinoma group (HCC) or a non-HCC group including liver cirrhosis, chronic hepatitis, and asymptomatic carriers. HBV serology, HBV-DNA level, and variations in core promoter/pre-core region were examined. Phylogenetic analysis based on the full genome sequences and nucleotide sequences partly in the S gene and in the P gene revealed that all Japanese strains (70/70) were subgenotype Ce, and nearly all of the Vietnamese strains (50/51) were subgenotype Cs, excluding one subgenotype C5. C1858 and G1775 were common in the Vietnamese (64% and 40%) but not in the Japanese (0%). The prevalence of C/A1753 in Vietnamese was higher than that in the Japanese (32% vs. 17.1%), however the frequency of A1896 in the Japanese was significantly higher (32.9% vs. 12%, P HBV-DNA, the Japanese HCC had a relatively low level. In the Vietnamese, C/A1753 and C1858 were associated closely with T1762A1764, higher HBV-DNA levels and higher HCC incidence. The multivariate analysis revealed that male, T1653 and C/A1753 were independent risk factors for HCC. The subgenotypes and unique mutations of HBV genotype C in the Vietnamese and Japanese differed, and C/A1753 and C1858 variants might play a role in the pathogenesis of liver disease in Vietnamese patients.

  11. Putative IL-10 Low Producer Genotypes Are Associated with a Favourable Etanercept Response in Patients with Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Heiko Schotte

    Full Text Available Outcome predictors of biologic therapeutic drugs like TNF inhibitors are of interest since side effects like serious infections or malignancy cannot be completely ruled out. Response rates are heterogeneous. The present study addressed the question whether in patients with rheumatoid arthritis (RA interleukin-10 (IL-10 promoter genotypes with potential relevance for IL-10 production capacity are associated with response to long-term treatment with etanercept. Caucasian RA patients that, according to the EULAR criteria, responded well (n = 25, moderately (n = 17 or not (n = 8 to etanercept therapy (median 36 months, range 4-52, and 160 matched controls were genotyped for the IL-10 promoter SNPs -2849 G>A (rs6703630, -1082 G>A (rs1800896, -819 C>T (rs1800871 and -592 C>A (rs1800872. Haplotypes were reconstructed via mathematic model and tested for associations with disease susceptibility and therapy response. We identified the four predominant haplotypes AGCC, GATA, GGCC, and GACC in almost equal distribution. Patients that responded well carried the putative IL-10 low producer allele -2849 A or the haplotypes AGCC and GATA (RR 2.1 and 4.0, respectively; 95% CI 1.1-4.0 and 1.1-14.8, whereas an unfavourable response was associated with carriage of the putative high producer haplotype GGCC (RR 1.9, 95% CI 1.1-3.3. No significant associations of alleles or haplotypes with disease susceptibility were observed. In RA, a low IL-10 production which is genetically determined rather by haplotypes than by SNPs may favour the response to etanercept treatment. Iatrogenic blockade of TNF may reveal proinflammatory effects of its endogeneous antagonist IL-10. Further studies are needed to correlate these genetic findings to direct cytokine measurements.

  12. Genotype-phenotype relationships in the low-phospholipid-associated cholelithiasis syndrome: a study of 156 consecutive patients.

    Science.gov (United States)

    Poupon, Raoul; Rosmorduc, Olivier; Boëlle, Pierre Yves; Chrétien, Yves; Corpechot, Christophe; Chazouillères, Olivier; Housset, Chantal; Barbu, Véronique

    2013-09-01

    The low-phospholipid-associated cholelithiasis syndrome (LPAC; OMIM 171060) is a peculiar form of intrahepatic cholelithiasis occurring in young adults, associated with ABCB4/MDR3 gene sequence variations. Our aim was to determine the genotype-phenotype relationships in 156 consecutive patients with the criteria of LPAC syndrome. A variant was detected in 79 (61 missense and 18 truncating sequence variants), 63 being monoallelic. The clinical features (age at onset, high prevalence in women, frequency and severity of acute and chronic complications, intrahepatic cholestasis of pregnancy [ICP]) were similar in the patients with or without ABCB4 gene sequence variation. Truncating variations were associated with an earlier onset of symptoms both in women and men. Acute and chronic biliary complications were variant-independent. Half of the women who had pregnancy developed ICP. The frequency of ICP and fetal complications were similar in patients with missense and truncating variants. The LPAC syndrome is more frequent in women and highly associated with ICP. Half of the patients harbored missense or truncating variants of the ABCB4 gene. The characteristics of the patients without detectable variant are similar to those with variant, indicating that yet unexplored regions of the ABCB4 and other genes may be involved. © 2013 by the American Association for the Study of Liver Diseases.

  13. Genotyping Analysis of Bitter-Taste Receptor Genes TAS2R38 and TAS2R46 in Japanese Patients with Gastrointestinal Cancers.

    Science.gov (United States)

    Yamaki, Michiko; Saito, Hiroki; Isono, Kunio; Goto, Tomoko; Shirakawa, Hitoshi; Shoji, Noriaki; Satoh-Kuriwada, Shizuko; Sasano, Takashi; Okada, Ryo; Kudoh, Katsuyoshi; Motoi, Fuyuhiko; Unno, Michiaki; Komai, Michio

    2017-01-01

    Type-2 bitter-taste receptors (TAS2Rs) are important for the evaluation of food quality and the nutritional control in animals. Mutations in some TAS2Rs including TAS2R38 are known to increase susceptibility to various diseases. However, the involvement of TAS2Rs in cancers has not been well understood. We conducted a pilot study by genotyping two TAS2R genes, TAS2R38 and TAS2R46, in Japanese cancer patients diagnosed with the following types of cancer: biliary tract cancer, hepatocellular carcinoma, pancreatic cancer, colorectal cancer and gastric cancer. We selected the two TAS2Rs because they carry virtually non-functional alleles in human populations. We found that cancer risk is not associated with any TAS2R46 genotypes since there were no significant differences in genotype frequencies between cancer patients and controls. On the other hand, we confirmed that phenylthiocarbamide (PTC) non-tasters homozygous (AVI/AVI) for TAS2R38 were more frequent among Japanese cancer patients than those among controls as suggested in a previous study. The AVI/AVI genotype was therefore considered to increases cancer risk. In contrast, we also found that homozygous (PAV/PAV) PTC tasters are less frequent among cancer patients, suggesting that the PAV/PAV is a cancer resistant genotype that decreases cancer risk. Genotype frequencies for heterozygous AVI/PAV genotype were not significantly different between the two groups. It is suggested that the risk and resistance of cancers is antagonistically controlled by the two TAS2R38 alleles, PAV and AVI, rather than by the AVI allele alone.

  14. The frequency of SLCO1B1*5 polymorphism genotypes among Russian and Sakha (Yakutia patients with hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Sychev DA

    2016-05-01

    Full Text Available Dmitrij Alekseevitch Sychev,1 Grigorij Nikolaevich Shuev,2 Jana Valer'evna Chertovskih,3 Nadezhda Romanovna Maksimova,3 Andrej Vladimirovich Grachev,1 Ol'ga Aleksandrovna Syrkova2 1Department of Internal Medicine and Clinical Pharmacology, Russian Medical Academy of Postgraduate Education, Moscow, 2Faculty of Postgraduate Education, Far Eastern State Medical University, Khabarovsk, 3Genetic Laboratory, Ammosov North-Eastern Federal University, Yakutsk, Russian Federation Introduction: Statins are the most commonly prescribed medicines for treatment of hypercholesterolemia. At the same time, up to 25% of patients cannot tolerate or have to discontinue the statin therapy due to statin-induced myopathy. In a majority of cases, statin-induced myopathy is attributed to SLCO1B1 gene polymorphism. The strongest association between statin-induced myopathy and SLCO1B1 gene polymorphism was described for simvastatin. Our research was focused on the frequency of SLCO1B1*5 genetic variant in the Russian population and in the native population of Sakha (Yakutia.Materials and methods: A total of 1,071 hyperlipidemic Russian and 76 hyperlipidemic Sakha (Yakutian patients were included in the study. Genotypes of SLCO1B1*5 (c.521T>C, rs4149056 were determined with polymerase chain reaction amplification. The results of our study were compared with data about hyperlipidemic patients in available publications.Results: In the Russian population 665 (62% patients had TT genotype of SLCO1B1*5, 346 (32% patients had TC genotype, and in 60 patients (6% CC variant was found (Hardy–Weinberg's chi-square test was 3.1 P=0.21. In comparison with Brazil, France, the People's Republic of China, Japan, and the native population of Sakha (Yakutia, C-allele, which causes an increased risk of statin-induced myopathy, was found significantly more often in the Russian population. In the native population of Sakha (Yakutia SLCO1B1 polymorphism was TT – 62 (82%, TC – 11 (14

  15. NOD2/CARD15 Gene Polymorphisms in Crohn's Disease: A Genotype-Phenotype Analysis in Danish and Portuguese Patients and Controls

    DEFF Research Database (Denmark)

    Vind, Ida; Vieira, A; Hougs, L;

    2005-01-01

    to a healthy background population and to compare genotype-phenotype relations in the two countries. METHODS: 58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were...... recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC. RESULTS: 22% of the Danish patients vs. 9% of Danish controls compared to 21% of the Portuguese patients vs. 16% had at least one mutation. Mutation rates...... in Danish patients were significantly different (p=0.02) compared with Danish controls, no difference (p=0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p=0.03) using...

  16. NOD2/CARD15 Gene Polymorphisms in Crohn's Disease: A Genotype-Phenotype Analysis in Danish and Portuguese Patients and Controls

    DEFF Research Database (Denmark)

    Vind, Ida; Vieira, A; Hougs, L

    2005-01-01

    to a healthy background population and to compare genotype-phenotype relations in the two countries. METHODS: 58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were...... recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC. RESULTS: 22% of the Danish patients vs. 9% of Danish controls compared to 21% of the Portuguese patients vs. 16% had at least one mutation. Mutation rates...... in Danish patients were significantly different (p=0.02) compared with Danish controls, no difference (p=0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p=0.03) using...

  17. ASSOCIATION OF THE NUTRITIONAL PROFILE WITH HISTOLOGICAL FINDINGS OF PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C INFECTION

    Directory of Open Access Journals (Sweden)

    Vanessa Aparecida de SANTIS E SILVA

    2015-12-01

    Full Text Available Background - Different factors are responsible for the progression of hepatic fibrosis in chronic infection with hepatitis C virus, but the role of nutritional factors in the progression of the disease is not clearly defined. This study aimed to evaluate the nutritional status and dietary profile among patients with chronic hepatitis C who were candidates for treatment and its association with histopathological features. Methods - A crossectional study was conducted on treatment-naïve patients with chronic hepatitis C genotype 1, between 2011 and 2013. The following assessments were performed before treatment: liver biopsy, anthropometric measurements and qualitative/quantitative analysis of food intake. Results - Seventy patients were studied. The majority of patients was classified as obese (34% or overweight (20% according to body mass index [BMI] and as at risk for cardiovascular diseases by waist circumference (79%. Unhealthy food intake was presented by 59% according to qualitative parameters and several patients showed an insufficient intake of calories (59%, excessive intake of protein (36% and of saturated fat (63%, according to quantitative analysis. With respect to histology, 68% presented activity grade ≥2, 65% had steatosis and 25% exhibited fibrosis stage >2. Comparative analysis between anthropometric parameters and histological features showed that elevated waist circumference was the only variable associated to hepatic steatosis ( P =0.05. There was no association between qualitative and quantitative food intake parameters with histological findings. Conclusion - In this study, most of the patients with hepatitis C presented inadequate qualitative food intake and excessive consumption of saturated fat; in addition, excess of abdominal fat was associated to hepatic steatosis. Therefore, nutritional guidance should be implemented prior to treatment in patients with chronic hepatitis C, in order to avoid nutritional disorders

  18. Killer immunoglobulin-like receptor (KIR) and KIR-ligand genotype do not correlate with clinical outcome of renal cell carcinoma patients receiving high-dose IL2.

    Science.gov (United States)

    Wang, Wei; Erbe, Amy K; Gallenberger, Mikayla; Kim, KyungMann; Carmichael, Lakeesha; Hess, Dustin; Mendonca, Eneida A; Song, Yiqiang; Hank, Jacquelyn A; Cheng, Su-Chun; Signoretti, Sabina; Atkins, Michael; Carlson, Alexander; Weiss, Jonathan M; Mier, James; Panka, David; McDermott, David F; Sondel, Paul M

    2016-12-01

    NK cells play a role in many cancer immunotherapies. NK cell activity is tightly regulated by killer immunoglobulin-like receptor (KIR) and KIR-ligand interactions. Inhibitory KIR-ligands have been identified as HLA molecules, while activating KIR-ligands are largely unknown. Individuals that have not inherited the corresponding KIR-ligand for at least one inhibitory KIR gene are termed the "KIR-ligand missing" genotype, and they are thought to have a subset of NK cells that express inhibitory KIRs for which the corresponding KIR-ligand is missing on autologous tissue, and thus will not be inhibited through KIR-ligand recognition. In some settings where an anticancer immunotherapeutic effect is likely mediated by NK cells, individuals with a KIR-ligand missing genotype have shown improved clinical outcome compared to individuals with an "all KIR-ligands present" genotype. In addition, patients receiving hematopoietic stem cell transplants for leukemia may do better if their donor has more activating KIR genes (i.e., KIR haplotype-B). In a recent multi-institution clinical trial of patients with metastatic renal cell carcinoma receiving high-dose IL2 (HD-IL2), 25 % of patients showed a complete or partial tumor response to this therapy. We genotyped KIR and KIR-ligand genes for these patients (n = 107) and tested whether KIR/KIR-ligand genotypes correlated with patient clinical outcomes. In these analyses, we did not find any significant association of KIR/KIR-ligand genotype (either KIR-ligand missing or the presence of KIR haplotype-B) with patient outcome in response to the HD-IL2 therapy.

  19. Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Hertz, Daniel L; Damkier, Per;

    2017-01-01

    -infiltrated tissues, all of which showed excellent CYP2D6 genotype agreement. We applied these concordance data to a quantitative bias analysis of the subset of the 31 studies that were based on genotypes from tumor-infiltrated tissue to examine whether genotyping errors substantially biased estimates of association....... The bias analysis showed negligible bias by discordant genotypes. Summary estimates of association, with or without bias adjustment, indicated no clinically important association between CYP2D6 genotype and breast cancer survival in tamoxifen-treated women....

  20. Experimental investigation of HFC407C/HC290/HC600a mixture in a window air conditioner

    Energy Technology Data Exchange (ETDEWEB)

    Jabaraj, D.B.; Avinash, P.; Lal, D. Mohan; Renganarayan, S. [Department of Mechanical Engineering, College of Engineering, Anna University, Chennai 600 025 (India)

    2006-09-15

    HCFC22, one of the widely used refrigerants in window air conditioners must be phased out soon as per the Montreal protocol. Presently, HFC407C is considered as a potential drop in substitute for HCFC22, but retrofitting HCFC22 systems with HFC407C with polyol ester oil (POE) is a major issue as HFC407C is immiscible with mineral oil. The miscibility issue of HFC407C with mineral oil was overcome with the addition of a HC blend to it. The above technoeconomic feasibility issues to retrofit the existing HCFC22 systems with an ozone friendly refrigerant and retain the energy efficiency of the system are challenges in the air conditioning sector. In this present work, an experimental analysis has been conducted in a window air conditioner retrofitted with eco-friendly refrigerant mixtures of HFC407C/HC290/HC600a without changing the mineral oil. Its performance, as well as energy consumption, was compared with the conventional one. It is observed that the mixtures demand lengthening of the condenser in order to maintain the discharge pressure within acceptable limits. This also resulted in better heat transfer at the condenser. Therefore, in this study, the condenser tube length was increased by 19% to suit the mixtures as compared to HCFC22. Compared to HCFC22, the refrigeration capacity of the new mixture was 9.54-12.76% higher than that of HCFC22, while the actual COP was found to be 11.91-13.24% higher than that of HCFC22. The overall performance has proved that the HFC407C/HC blend refrigerant mixture could be an eco-friendly substitute to phase out HCFC22. (author)

  1. Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes

    DEFF Research Database (Denmark)

    Østergaard, Jakob A; Thiel, Steffen; Lajer, Maria

    2015-01-01

    OBJECTIVE: Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore...... are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations....... aimed to investigate this. RESEARCH DESIGN AND METHODS: We studied an existing 12-year prospective cohort with type 1 diabetes with 198 patients with diabetic nephropathy (121 men, age 41 years [95% CI 40-42], estimated glomerular filtration rate [eGFR] 67 mL/min/1.73 m(2) [95% CI 63-70]) and 174...

  2. Negotiating substance use stigma: the role of cultural health capital in provider-patient interactions.

    Science.gov (United States)

    Chang, Jamie; Dubbin, Leslie; Shim, Janet

    2016-01-01

    Diverse aspects of life and lifestyles, including stigmatised attributes and behaviors are revealed as providers and patients discuss health. In this article, we examine how the stigma associated with substance use issues shapes clinical interactions. We use the theoretical framework of cultural health capital (CHC) to explain how substance use stigma is created, reinforced and sometimes negotiated as providers and patients engage in health interactions. We present two main findings using examples. First, two theoretical concepts--habitus and field--set the social position and expectations of providers and patients in ways that facilitate the stigmatisation of substance use. Second, we found both providers and patients actively exchanged CHC as a key strategy to reduce the negative effects of stigma. In some clinical encounters, patients possessed and activated CHC, providers acknowledged patient's CHC and CHC was successfully exchanged. These interactions were productive and mutually satisfying, even when patients were actively using substances. However, when CHC was not activated, acknowledged and exchanged, stigma was unchallenged and dominated the interaction. The CHC theoretical framework allows us to examine how the stigma process is operationalized and potentially even counteracted in clinical interactions. © 2015 Foundation for the Sociology of Health & Illness.

  3. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, Louise B; Kronborg, Gitte

    2007-01-01

    OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients...... with increased mortality (mortality rate ratio [MRR] 2.3 [95% confidence interval (CI) 1.1-4.8]), as were the individual mutations T215Y (MRR 3.4 [95% CI 1.6-7.0]), G190A/S (MRR 3.2 [95% CI 1.6-6.6]) and V82F/A/T/S (MRR 2.5 [95% CI 1.2-5.3]). CONCLUSIONS: In HIV patients with TCF, the total number of genotypic...... resistance mutations and specific single mutations predicted mortality.OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish...

  4. The 4G/4G Genotype of PAI-1 Polymorphism Is Associated with Higher Plasma PAI-1 Concentrations and Mortality in Patients with Severe Sepsis.

    Science.gov (United States)

    Lorente, Leonardo; Martín, María M; Borreguero-León, Juan M; Barrios, Ysamar; Solé-Violán, Jordi; Ferreres, José; Labarta, Lorenzo; Díaz, César; Jiménez, Alejandro

    2015-01-01

    Two studies have reported that patients with the 4G/4G genotype of the plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism had higher plasma PAI-1 concentrations and higher risk of death than those with the 4G/5G or 5G/5G genotypes; one study involved 175 children with meningococcal disease, and the other included 88 adult patients with septic shock. Thus, the objective of this study was to determine whether there is an association between carriage of the 4G/4G genotype, plasma PAI-1 concentrations and mortality in a large series of adult septic patients. An observational, prospective, multicenter study was carried out in six Spanish Intensive Care Units including severe septic patients. We determined the PAI-1 4G/5G polymorphism and plasma PAI-1 concentrations in all patients. The end-points of the study were 30-day and 6-month mortality. We included a total of 260 patients, 82 (31.5%) with 4G/4G, 126 (48.5%) with 4G/5G and 52 (20.0%) with 5G/5G genotype. Multivariate logistic regression analysis showed that the 4G/4G genotype was associated with higher mortality at 30 days (Odds Ratio = 1.95; 95% CI = 1.063-3.561; p = 0.03) and at 6 months (Odds Ratio = 2.19; 95% CI = 1.221-3.934; p = 0.01), and that higher plasma PAI-1 concentrations were associated with higher mortality at 30 days (Odds Ratio = 1.01; 95% CI = 1.002-1.022; p = 0.02) at 6 months (Odds Ratio = 1.01; 95% CI = 1.003-1.023; p = 0.01). Multivariate linear regression analysis showed that increased plasma PAI-1 concentrations were associated with the PAI-1 4G/4G genotype (regression coefficient = 4.82; 95% CI = 3.227 to 6.406; p4G/5G polymorphism of the PAI-1 gene, plasma PAI-1 concentrations and mortality in septic patients, were that septic patients with the 4G/4G genotype had higher plasma PAI-1 concentrations and higher risk of death than those with 4G/5G or 5G/5G genotypes.

  5. A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus.

    Science.gov (United States)

    Ahn, S H; Lim, Y S; Lee, K S; Paik, S W; Lee, Y J; Jeong, S H; Kim, J H; Yoon, S K; Yim, H J; Tak, W Y; Han, S Y; Yang, J C; Mo, H; Mathias, A; Han, L; Knox, S J; Brainard, D M; Kim, Y J; Byun, K S; Kim, Y S; Heo, J; Han, K H

    2016-05-01

    In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.

  6. Genotyping of samples from German patients with ocular, cerebral and systemic toxoplasmosis reveals a predominance of Toxoplasma gondii type II.

    Science.gov (United States)

    Herrmann, Daland C; Maksimov, Pavlo; Hotop, Andrea; Groß, Uwe; Däubener, Walter; Liesenfeld, Oliver; Pleyer, Uwe; Conraths, Franz J; Schares, Gereon

    2014-10-01

    Toxoplasmosis is an important zoonosis transmitted from animals to humans world-wide. In order to determine Toxoplasma gondii genotypes in individuals living in Germany and to compare findings with those in animals, we analysed nine independent and unlinked genetic markers (nSAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) by PCR-RFLP in 83 archived T. gondii-positive DNA samples from patients with ocular toxoplasmosis (n=35), toxoplasmic encephalitis (n=32), systemic toxoplasmosis after bone-marrow transplantation (n=15) and congenital toxoplasmosis (n=1). In 46 of these 83 samples the presence of T. gondii DNA was confirmed by conventional end-point PCR. Among these, 17 T. gondii-positive samples were typed at all nine loci. The majority (15/17, 88.2%) of these samples were of T. gondii type II (i.e., including both, the Apico type II and Apico type I variants). In addition, in one sample a T. gondii type II/type III allele combination and in another sample a T. gondii genotype displaying type III alleles at all markers was observed. In the remaining 11 samples, in which T. gondii could only be partially typed, exclusively type II (n=10) or type III (n=1) alleles were observed. Results of the present study suggest that the majority of patients in Germany are infected with type II T. gondii regardless of the clinical manifestation of toxoplasmosis. This finding is in accord with the predominance of type II T. gondii in oocysts isolated from cats and in tissues of other intermediate hosts in Germany.

  7. The CYP2C19*17 genotype is associated with lower imipramine plasma concentrations in a large group of depressed patients.

    Science.gov (United States)

    Schenk, P W; van Vliet, M; Mathot, R A A; van Gelder, T; Vulto, A G; van Fessem, M A C; Verploegh-Van Rij, S; Lindemans, J; Bruijn, J A; van Schaik, R H N

    2010-06-01

    CYP2C19 converts the tricyclic antidepressant imipramine to its active metabolite desipramine, which is subsequently inactivated by CYP2D6. The novel CYP2C19*17 allele causes ultrarapid metabolism of CYP2C19 substrates. We genotyped 178 depressed patients on imipramine for CYP2C19*17, and measured steady-state imipramine and desipramine plasma concentrations. Mean dose-corrected imipramine plasma concentration was significantly dependent on CYP2C19 genotype (Kruskal-Wallis test, P=0.01), with circa 30% lower levels in CYP2C19*17/*17 individuals compared with CYP2C19*1/*1 (wild-type) patients. The mean dose-corrected imipramine+desipramine plasma concentrations and imipramine/desipramine ratios were not significantly different between genotype subgroups (Kruskal-Wallis tests, P>or=0.12). In a multivariate analysis, we found a significant, but limited effect (P=0.035, eta(2)=0.031) of the CYP2C19*17 genotype on imipramine+desipramine concentrations. Although the CYP2C19*17 allele is associated with a significantly increased metabolism of imipramine, CYP2C19*17 genotyping will, in our view, not importantly contribute to dose management of patients on imipramine therapy guided by imipramine+desipramine plasma concentrations.

  8. Mutation spectrum and genotype-phenotype correlation of hearing loss patients caused by SLC26A4 mutations in the Japanese: a large cohort study.

    Science.gov (United States)

    Miyagawa, Maiko; Nishio, Shin-Ya; Usami, Shin-Ichi

    2014-05-01

    Mutations in SLC26A4 cause a broad phenotypic spectrum, from typical Pendred syndrome to nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Identification of these mutations is important for accurate diagnosis, proper medical management and appropriate genetic counseling and requires updated information regarding spectrum, clinical characteristics and genotype-phenotype correlations, based on a large cohort. In 100 patients with bilateral enlarged vestibular aqueduct among 1511 Japanese hearing loss probands registered in our gene bank, goiter data were available for 79, of whom 15 had Pendred syndrome and 64 had nonsyndromic hearing loss. We clarified the mutation spectrum for the SLC26A4 mutations and also summarized hearing levels, progression, fluctuation and existence of genotype-phenotype correlation. SLC26A4 mutations were identified in 82 of the 100 patients (82.0%). Of the Pendred syndrome patients, 93% (14/15) were carriers, as were 77% (49/64) of the nonsyndromic hearing loss patients. Clinical characteristics of patients with SLC26A4 mutations were congenital, fluctuating and progressive hearing loss usually associated with vertigo and/or goiter. We found no genotype-phenotype correlations, indicating that, unlike in the case of GJB2 mutations, the phenotype cannot be predicted from the genotype. Our mutation analysis confirmed the importance of mutations in the SLC26A4 gene among hearing loss patients with enlarged vestibular aqueduct and revealed the mutation spectrum, essential information when performing genetic testing.

  9. Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study.

    Science.gov (United States)

    Petta, Salvatore; Marzioni, Marco; Russo, Pierluigi; Aghemo, Alessio; Alberti, Alfredo; Ascione, Antonio; Antinori, Andrea; Bruno, Raffaele; Bruno, Savino; Chirianni, Antonio; Gaeta, Giovanni Battista; Giannini, Edoardo G; Merli, Manuela; Messina, Vincenzo; Montilla, Simona; Perno, Carlo Federico; Puoti, Massimo; Raimondo, Giovanni; Rendina, Maria; Silberstein, Francesca Ceccherini; Villa, Erica; Zignego, Anna Linda; Pani, Luca; Craxì, Antonio

    2017-06-01

    We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83-12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. Our findings

  10. Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Gattu Mahanandeeshwar

    2007-07-01

    Full Text Available Abstract Background Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC virus infection and fibrosis. Methods Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1 and 23 with advanced fibrosis (F3, F4 were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups. Results Seven individual protein spots were identified as either significantly increased (α2-macroglobulin, haptoglobin, albumin or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α2-macroglobulin, are included in existing non-invasive serum marker panels. Conclusion Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.

  11. Identification of HIV-1 Genotypic Resistance in Patients on First-line Antiretroviral Therapy Using Polymerase Chain Reaction and Sequencing

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Objective The aim of the study was to evaluate the characteristics of HIV drug-genotypic resistance among patients taking ifrst-line ARV regimens using polymerase chain reaction and sequencing, and guide to design optimal ARV regimens for these patients. Methods HIV reverse transcriptase-encoded gene was ampliifed with RT-PCR and ampliifed PCR products were aligned and comparatively analyzed with HIV resistance database to ifnd drug-resistance mutations. Results Twenty-eight PCR products were amplified and sequenced successfully in 30 serum samples of recruited HIV-infected patients with virologic failure. The resistance rate was 96%, mutations in NRT region were found in 26 patients (93%), while mutations in NNRT region were found in 27 patients (96%). M184V was the most common mutation (86%), K65R was selected in 14%of recruited individuals and TAMs occurred in 50%of patients, which resulted in resistance to NRTIs. Y181C and V179D were the most common mutations in NNRTIs and prevalence was 43%(12/28) and 36%(10/28), respectively, which resulted in cross-resistance to NNRTIs due to low-genetic barrier. Conclusions Virologic failure may occur in long-term administration of ifrst-line ARV regimens, and drug-resistance mutations can be found in these patients, which resulted in resistance to ifrst-line ARV regimens. We emphasized that HIV viral load assay and resistance assay were important tools to guide healthcare workers to design an optimal second-line ARV regimens for HAART-experienced individuals with virologic failure.

  12. HLA-DRB1 alleles genotyping in patients with rheumatoid arthritis in Chinese.

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    Objective: To explore the role of HLA-DRB1 genes in the development of rheumatoid arthritis (RA) and the correlations between HLA-DR alleles and clinical manifestations of patients with RA. Methods: 86 patients and 106 race matched controls in whom HLADR typing was performed by the method of DNA amplification with sequence-specific primers (PCR-SSP)

  13. Hepatitis C virus long-term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1.

    Science.gov (United States)

    Parodi, C; García, G; Monzani, M C; Culasso, A; Aloisi, N; Corti, M; Campos, R; de E de Bracco, M M; Baré, P

    2015-07-01

    Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.

  14. Health-related quality of life in adult dermatitis patients stratified by filaggrin genotype

    DEFF Research Database (Denmark)

    Heede, Nina G; Thyssen, Jacob P; Thuesen, Betina H

    2017-01-01

    . METHODS: This cross-sectional study included patients diagnosed with atopic dermatitis and/or hand eczema (n = 520). Patients completed questionnaires about dermatitis, skin symptoms, HRQoL, and comorbidities, including actinic keratosis, and atopic and mental disorders. RESULTS: FLG mutations (R501X......, 2282del4, and R2447X) were identified in 16.9% of patients, and were significantly associated not only with atopic dermatitis, but also independently with skin fissures on the fingers and heels, and self-reported actinic keratosis. Although FLG mutations were significantly associated with reduced HRQo......L, as measured by use of the Dermatology Life Quality Index (DLQI), no association with self-reported anxiety or depression was identified. Notably, the highest median DLQI score, reflecting greater impairment, was reported by patients with both FLG mutations and atopic dermatitis. Overall, 19.7% of patients...

  15. Amplification refractory mutation system polymerase chain reaction versus optimized polymerase chain reaction restriction-fragment length polymorphism for apolipoprotein E genotyping of majorly depressed patients.

    Science.gov (United States)

    You, Hongmin; Chen, Jin; Zhou, Jingjing; Huang, Hua; Pan, Junxi; Wang, Ziye; Lv, Lin; Zhang, Lujun; Li, Juan; Qin, Bin; Yang, Yongtao; Xie, Peng

    2015-11-01

    Major depressive disorder (MDD) is a prevalent, debilitating mood disorder that has been associated with several genetic polymorphisms. One such polymorphism, namely that of apolipoprotein E (APOE), has three allelic forms (ε2, ε3 and ε4) that encode for six unique isoforms of the APOE protein. A growing number of techniques have been developed for APOE genotyping; however, not all polymerase chain reaction (PCR)‑based genotyping techniques are equally accurate or cost‑effective. In order to find a more accurate and cost‑effective APOE genotyping method for MDD screening in large populations, the present study comparatively evaluated two genotyping methods, amplification refractory mutation system PCR (ARMS‑PCR) and optimized PCR restriction‑fragment length polymorphism (PCR‑RFLP), in blood samples taken from a population of 708 MDD patients. Although either of the two methods were able to detect all six unique APOE genotypes, comparisons of the two methods with Sanger sequencing demonstrated that ARMS‑PCR (94%) was significantly more accurate than optimized PCR‑RFLP (82%). ARMS‑PCR should prove useful in quickly verifying ambiguous results obtained by other APOE genotyping methods and can be cost-effectively performed in the setting of a small laboratory or a population-based screening program.

  16. Global, Broad, or Specific Cognitive Differences? Using a MIMIC Model to Examine Differences in CHC Abilities in Children with Learning Disabilities

    Science.gov (United States)

    Niileksela, Christopher R.; Reynolds, Matthew R.

    2014-01-01

    This study was designed to better understand the relations between learning disabilities and different levels of latent cognitive abilities, including general intelligence (g), broad cognitive abilities, and specific abilities based on the Cattell-Horn-Carroll theory of intelligence (CHC theory). Data from the "Differential Ability…

  17. Comparing Models of Intelligence in Project TALENT: The VPR Model Fits Better than the CHC and Extended Gf-Gc Models

    Science.gov (United States)

    Major, Jason T.; Johnson, Wendy; Deary, Ian J.

    2012-01-01

    Three prominent theories of intelligence, the Cattell-Horn-Carroll (CHC), extended fluid-crystallized (Gf-Gc) and verbal-perceptual-image rotation (VPR) theories, provide differing descriptions of the structure of intelligence (McGrew, 2009; Horn & Blankson, 2005; Johnson & Bouchard, 2005b). To compare these theories, models representing them were…

  18. Patients receiving opioid maintenance treatment in primary care: successful chronic hepatitis C care in a real world setting

    Directory of Open Access Journals (Sweden)

    Seidenberg André

    2013-01-01

    Full Text Available Abstract Background Injection drug users (IDUs represent a significant proportion of patients with chronic hepatitis C (CHC. The low treatment uptake among these patients results in a low treatment effectiveness and a limited public health impact. We hypothesised that a general practitioner (GP providing an opioid maintenance treatment (OMT for addicted patients can achieve CHC treatment and sustained virological response rates (SVR comparable to patients without drug dependency. Methods Retrospective patient record analysis of 85 CHC patients who received OMT for more than 3 months in a single-handed general practice in Zurich from January 1, 2002 through May 31, 2008. CHC treatment was based on a combination with pegylated interferon and ribavirin. Treatment uptake and SVR (undetectable HCV RNA 6 months after end of treatment were assessed. The association between treatment uptake and patient characteristics was investigated by multiple logistic regression. Results In 35 out of 85 CHC patients (52 males with a median (IQR age of 38.8 (35.0-44.4 years, antiviral therapy was started (41.2%. Median duration (IQR of OMT in the treatment group was 55.0 (35.0-110.1 months compared to the group without therapy 24.0 (9.8-46.3 months (p Conclusion In addicted patients a high CHC treatment and viral eradication rate in a primary care setting in Switzerland is feasible. Opioid substitution seems a beneficial framework for CHC care in this “difficult to treat” population.

  19. Co-infection of SENV-D among chronic hepatitis C patients treated with combination therapy with high-dose interferon-alfa and ribavirin

    Institute of Scientific and Technical Information of China (English)

    Chia-Yen Dai; Liang-Yen Wang; Ming-Lung Yu; Wan-Long Chuang; Wen-Yu Chang; Shinn-Cherng Chen; Li-Po Lee; Ming-Yen Hsieh; Nei-Jen Hou; Zu-Yau Lin; Ming-Yuh Hsieh

    2005-01-01

    AIM: The clinical significance of co-infection of SENV-D among patients with chronic hepatitis C (CHC) and response of both viruses to combination therapy with high-dose interferon-alfa (IFN) plus ribavirin remain uncertain and are being investigated.METHODS: Total 164 (97 males and 67 females, the mean age 48.1±11.4 years, range: 20-73 years, 128histologically proved) naive CHC patients were enrolled in this study. SENV-D DNA was tested by PCR method.Detection of serum HCV RNA was performed using a standardized automated qualitative RT-PCR assay (COBAS AMPLICOR HCV Test, version 2.0). HCV genotypes 1a,1b, 2a, 2b, and 3a were determined by using genotypespecific primers. Pretreatment HCV RNA levels were determined by using the branched DNA assay (Quantiplex HCV RNA 3.0). There are 156 patients receiving combination therapy with IFN 6 MU plus ribavirin for 24 wk and the response to therapy is determined.RESULTS: Sixty-one (37.2%) patients were positive for SENV-D DNA and had higher mean age than those who were negative (50.7±10.6 years vs46.6±11.6 years,P = 0.026). The rate of sustained viral response (SVR)for HCV and SENV-D were 67.3% (105/156) and 56.3%(27/48), respectively. By univariate analysis, the higher rate of SVR was significantly related to HCV genotype non-1b (P<0.001), younger ages (P = 0.014), lower pretreatment levels of HCV RNA (P = 0.019) and higher histological activity index (HAI) score for intralobular regeneration and focal necrosis (P = 0.037). By multivariate analyses, HCV genotype non-1b, younger age and lower pretreatment HCV RNA levels were significantly associated with HCV SVR (odds ratio (OR)/95% confidence interval (CI): 12.098/0.02-0.19, 0.936/0.890-0.998, and 3.131/1.080-9.077, respectively). The SVR of SENV-D was higher among patients clearing SENV-D than those who had viremia at the end of therapy (P = 0.04).CONCLUSION: Coexistent SENV-D infection, apparently associated with higher ages, is found in more than onethird Taiwanese

  20. The relationship between genotype, psychiatric symptoms and quality of life in adult patients with sickle cell disease in São Paulo, Brazil: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Érika Bergamini Mastandréa

    Full Text Available CONTEXT AND OBJECTIVE: Health-related quality of life (HRQoL may be worsened in sickle cell patients due to the presence of psychiatric disorders. The aims of this study were to describe the psychiatric symptoms in Brazilian sickle cell patients and to evaluate the relationship of these symptoms to the genotype of the disease and the subject's HRQoL. DESIGN AND SETTING: Cross-sectional study conducted at the hematology outpatient clinic, Hospital São Paulo. METHODS: Adult patients with sickle cell disease completed the Medical Outcome Study - Short Form 36 and the Patients' Health Questionnaire. Clinical data were gathered from their medical files. Linear regression models were developed to study the dependency of HRQoL domains on the genotype controlling for psychiatric symptoms. RESULTS: In the study period, 110 patients were evaluated. The most frequent psychiatric symptom was depression (30%, followed by anxiety (12.7% and alcohol abuse (9.1%. Patients with the more severe genotype (SS and Sβthal0 showed lower scores for the "general health" and "role-physical" HRQoL domains, without interference from psychiatric symptoms. In the "role-physical" domain, the more severe genotype operated as a protective factor for HRQoL (β = 0.255; P = 0.007. CONCLUSION: The more severe genotypes worsened HRQoL in two domains of physical health (general health and role-physical, but they did not have any influence on mental health, thus suggesting that physicians should be more attentive to aspects of HRQoL relating to the functionality of sickle cell disease patients, so as to be aware of the limitations that these patient live with.

  1. Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial

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    Picardi Antonio

    2010-02-01

    Full Text Available Abstract Background In patients with chronic hepatitis C virus (HCV genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha and ribavirin induces a sustained virological response (SVR in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR. The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment. Methods Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week and ribavirin (800-1200 mg/day for 4 weeks. Patients with a RVR (HCV RNA not detectable were randomized (1:1 to either 12 (group A1 or 24 (group A2 weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B. HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment. Results At study end, end of treatment response (ETR was observed in 62 (86% patients of group A1 and in 55 (77% patients of group A2 (p Conclusion In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR. Trial registration Trial number ISRCTN29259563

  2. Genotype-phenotype correlation in cystic fibrosis patients compound heterozygous for the A455E mutation.

    Science.gov (United States)

    De Braekeleer, M; Allard, C; Leblanc, J P; Simard, F; Aubin, G

    1997-12-01

    Cystic fibrosis (CF) has a high incidence in the French-Canadian population of Saguenay Lac-Saint-Jean (Quebec). The A455E mutation accounts for 8.3% of the CF chromosomes. This mutation was shown to be associated with a milder lung disease in the Dutch population. Twenty two CF patients distributed in 17 families and compound heterozygotes for the A455E mutation have been followed at the Clinique de Fibrose Kystique de Chicoutimi. Fourteen patients also carried the delta F508 mutation while the remaining eight patients had the 621 + 1G-->T mutation. Each patient was matched by sex and age to a patient homozygous for the delta F508 mutation. The pairs were analyzed for several clinical and laboratory variables. The A455E compound heterozygotes were diagnosed at a later age (P = 0.003) and had chloride concentrations at the sweat test lower than those homozygous for the delta F508 mutation (P = 0.007). More patients were pancreatic sufficient (P = 0.004). They had a higher Shwachman score (P = 0.001) and better pulmonary function tests (P < 0.02). CF patients compound heterozygous for the A455E mutation have a milder pancreatic and lung disease than the delta F508 homozygotes. Therefore, the A455E should be associated with a better prognosis.

  3. Negotiating substance use stigma: the role of cultural health capital in provider–patient interactions

    Science.gov (United States)

    Chang, Jamie; Dubbin, Leslie; Shim, Janet

    2016-01-01

    Diverse aspects of life and lifestyles, including stigmatised attributes and behaviors are revealed as providers and patients discuss health. In this article, we examine how the stigma associated with substance use issues shapes clinical interactions. We use the theoretical framework of cultural health capital (CHC) to explain how substance use stigma is created, reinforced and sometimes negotiated as providers and patients engage in health interactions. We present two main findings using examples. First, two theoretical concepts – habitus and field – set the social position and expectations of providers and patients in ways that facilitate the stigmatisation of substance use. Second, we found both providers and patients actively exchanged CHC as a key strategy to reduce the negative effects of stigma. In some clinical encounters, patients possessed and activated CHC, providers acknowledged patient’s CHC and CHC was successfully exchanged. These interactions were productive and mutually satisfying, even when patients were actively using substances. However, when CHC was not activated, acknowledged and exchanged, stigma was unchallenged and dominated the interaction. The CHC theoretical framework allows us to examine how the stigma process is operationalized and potentially even counteracted in clinical interactions. PMID:26382837

  4. Data on IL-6 c.-174 G>C genotype and allele frequencies in patients with coronary heart disease in dependence of cardiovascular outcome

    Directory of Open Access Journals (Sweden)

    Stefan Reichert

    2016-09-01

    Full Text Available In this data article we present data on the distribution of alleles and genotypes of the interleukin (IL-6 c.-174 G>C polymorphism (rs 1800795 in patients with coronary heart disease (CHD in dependence of the incidence of new cardiovascular events (combined endpoint: myocardial infarction, stroke/TIA, cardiac death, death according to stroke within three years follow-up. Moreover, we investigated putative associations between individual expression of IL-6 genotypes and IL-6 serum level. This investigation is a subanalysis of the article entitled “The Interleukin 6 c.-174 CC genotype is a predictor for new cardiovascular events in patients with coronary heart disease within three years follow-up“ (ClinicalTrials.gov identifier: NCT01045070 (Reichert et al., 2016 [1].

  5. Inflammatory effects of blood leukocytes: association with vascular function in neuropeptide Y proline 7-genotyped type 2 diabetes patients.

    Science.gov (United States)

    Kakko, Tanja; Jaakkola, Ulriikka; Raitakari, Olli T; Kallio, Jaana

    2011-07-01

    We investigated the associations of inflammatory blood cell activation with vascular parameters in patients with type 2 diabetes to elucidate the possible mechanisms of accelerated atherosclerosis observed in subjects with the Leucine 7 to Proline 7 polymorphism (Leu7Pro) in the neuropeptide Y (NPY). Our study included 31 Caucasian patients with type 2 diabetes; 12 of them had the Leu7Pro7 (heterozygous), and 19 had the Leu7Leu7 (wild type) genotype. Vascular parameters were determined by ultrasound methods. Leukocyte analyses were performed from blood samples using flow cytometry. NPY concentrations were determined in plasma. The amount of platelet-granulocyte complexes was positively correlated with NPY concentration (p=0.008) and carotid intima-media thickness (p=0.035) in the Leu7Pro7 group. Interferon gamma (IFN-γ) expression in monocytes correlated negatively with brachial artery flow-mediated dilatation also in the Leu7Pro7 group (p=0.037). The expression of tissue factor on monocytes correlated negatively with brachial artery diameter in the Leu7Pro7 patients as well (p=0.019). The results indicate significant associations between inflammatory cell activation in blood and vascular atherosclerosis in genetically prone subjects, and provide possible mechanistic information about the role of NPY and the Leu7Pro polymorphism in the development of atherosclerosis.

  6. Molecular diversity in irregular or refugee immigrant patients with HBV-genotype-E infection living in the metropolitan area of Naples.

    Science.gov (United States)

    Sagnelli, Caterina; Ciccozzi, Massimo; Coppola, Nicola; Minichini, Carmine; Lo Presti, Alessandra; Starace, Mario; Alessio, Loredana; Macera, Margherita; Cella, Eleonora; Gualdieri, Luciano; Caprio, Nunzio; Pasquale, Giuseppe; Sagnelli, Evangelista

    2016-11-02

    In a recent testing in the metropolitan area of Naples, Italy, on 945 irregular immigrants or refugees, 87 HBsAg chronic carriers were identified, 53 of whom were infected by HBV-genotype E. The aim of the present study was to identify the genetic diversity of HBV-genotype E in these 53 immigrants. The 53 immigrant patients with HBV-genotype-E infection were born in Africa, central or eastern Asia, eastern Europe or Latin America. These patients had been seen for a clinical consultation at one of the four first-level units from January 2012 to 2013. The first dataset contained 53 HBV-S gene isolates plus 128 genotype/subgenotype specific reference sequences downloaded from the National Center for Biotechnology Information. The second dataset, comprising the 53 HBV-S gene isolates, previously classified as HBV-genotype E, was used to perform the time-scaled phylogeny reconstruction using a Bayesian approach. Phylogenetic analysis showed that all 53 HBV-S isolates belonged to HBV-genotype E. Bayes factor analysis showed that the relaxed clock exponential growth model fitted the data significantly better than the other models. The time-scaled Bayesian phylogenetic tree of the second dataset showed that the root of the tree dated back to the year 1990 (95% HPD:1984-2000). Four statistically supported clusters were identified. Cluster A dated back to 2012 (95% HPD:1997-2012); cluster B dated back to 2008 (95% HPD:2001-2015); cluster C to 2006 (95% HPD:1999-2013); cluster D to 2004 (95% HPD:1998-2011). This study disclosed the genetic evolution and phylogenesis in a group of HBV-genotype-E-infected immigrants. J. Med. Virol. © 2016 Wiley Periodicals, Inc.

  7. The presence of PAI-1 4G/5G and ACE DD genotypes increases the risk of early-stage AVF thrombosis in hemodialysis patients.

    Science.gov (United States)

    Güngör, Yahya; Kayataş, Mansur; Yıldız, Gürsel; Özdemir, Öztürk; Candan, Ferhan

    2011-01-01

    In this study, we investigated the relationship between early arteriovenous fistula (AVF) thrombosis with angiotensin-converting enzyme (ACE) gene and thrombophilic factor gene polymorphisms. Thirty-five patients who suffered from three or more fistula thrombosis episodes in the early period after AVF operation and 33 control patients with no history of thrombosis for at least 3 years were enrolled in this study. Factor V G1691A Leiden, factor V H1299R (R2), prothrombin G20210A, factor XIIIV34L, β-fibrinogen-455 G-A, glycoprotein IIIa L33P human platelet antigens (HPA-1), methylenetetrahydrofolate reductase C677T, and methylenetetrahydrofolate reductase A1298C gene polymorphisms were similar in both groups (p > 0.05). Plasminogen activator inhibitor 1 (PAI-1) 4G/5G genotype in the study group and 4G/4G genotype in the control group were significantly higher (p = 0.014). No significant difference was detected in terms of the 5G/5G genotype. With regard to the ACE gene polymorphism, the control group showed more ID genotype (19/33, 57.6%), whereas the study group showed more DD genotype (17/35, 48.6%). II genotype was similar in both groups (x(2) = 7.40, p = 0.025). The rate of ACE inhibitor-angiotensin II receptor blockers use was 5/35 in the study group (14.3%) and 5/33 in the control group (15.2%). Individuals with PAI-1 4G/5G genotype showed 5.03 times more risk of thrombosis when compared with 4G/4G and 5G/5G genotypes [p = 0.008, OR = 5.03, 95% confidence interval (1.44:17.64)]. Individuals with ACE DD genotype showed 4.25 times more risk of thrombosis when compared with II and ID [p = 0.008, OR = 4.25, 95% confidence interval (1.404:12.83)]. PAI-1 4G/5G and ACE DD genotypes are associated with increased risk for early AVF thrombosis.

  8. Mutational analysis of ATP7B gene and the genotype-phenotype correlation in patients with Wilson's disease in Serbia

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    Tomić Aleksandra

    2013-01-01

    Full Text Available Background/Aim. Wilson’s disease (WD is an autosomal-recessive disorder which is characterized with a marked clinical heterogeneity. The gene responsible for WD is located in 13q14.3 chromosome, contains 21 exons and codes for copper specific transporting P-type adenosinetriphosphatase (ATPase (ATP7B. Mutations in ATP7B gene change biosynthetic and transporting role of ATPase in cell leading to damaged billiary excretion of copper and its accumulation in the liver, brain, cornea and other tissues. Until now, it has been described more than 400 mutations in ATP7B gene with characteristic geographic distribution. The aim of this study was to assess the spectrum of mutations of ATP7B gene on a large number of patients in Serbian population and to make a correlation between particular genotypes and specific phenotypes. Methods. Eighty-six consecutive patients with WD from WD Clinical Research programme were included in this study. Genetic analysis was performed by direct gene sequencing method. Results. Mutations in ATP7B gene were found in 93% analyzed patients (81.4% of all alleles analyzed. Thirteen mutations were identified, one of which (G998E was the novel one, so far undescribed in the literature. The most frequent mutation in our population was H1069Q, which was present in 38.4% patients, and the second most frequent mutation was 2304-2305insC (11.6%. Also, a great number of gene polymorphisms of DNA sequences, which do not disturb the ATP7B gene function, was identified. Although neurological form of the disease was more frequent in the group of homozygous for H1069Q and the group of non- H1069Q carriers, there was no statistically significant difference between the groups. Conclusion. Our research showed that genetic diagnosis of WD can be done in 80% of cases by analysis of 5 most common mutations in our population, which facilitate diagnosis significantly. There was no correlation between different genotypes and specific phenotypic

  9. Early predictive efficacy of core antigen on antiviral outcomes in genotype 1 hepatitis C virus infected patients

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    Bo Feng

    Full Text Available Response-guided therapy is of limited use in developing countries because hepatitis C virus RNA detection by sensitive molecular methods is time- and labor-consuming and expen- sive. We evaluated early predictive efficacy of serum hepatitis C virus core antigen kinetics on sustained virologic response in patients with genotype 1 hepatitis C virus during pegylated interferon plus ribavirin treatment. For 478 patients recruited, hepatitis C virus RNAs were detected at baseline, and at weeks 4, 12, 24, 48, and 72 using Cobas TaqMan. Architect hepatitis C virus core antigen was performed at baseline, and weeks 4 and 12. Predictive values of hepatitis C virus core antigen on sustained virologic response were compared to hepatitis C virus RNA. In the first 12 weeks after treatment initiation the dynamic patterns of serum hepatitis C virus core antigen and hepatitis C virus RNA levels were similar in sustained virologic response, relapse, and null response patients groups. Although areas under the receiver operating characteristics curves of hepatitis C virus core antigen were lower than those of hepatitis C virus RNA at the same time points, modeling analysis showed that undetectable hepatitis C virus core antigen (rapid virological response based on hepatitis C virus core antigen had similar positive predictive value on sustained virologic response to hepatitis C virus RNA at week 4 (90.4% vs 93.3%, and hepatitis C virus core antigen decrease greater than 1 log10 IU/mL (early virological response based on hepatitis C virus core antigen had similar negative predictive value to hepatitis C virus RNA at week 12 (94.1% vs 95.Z%. Analysis on the validation group demonstrated a positive predictivevalue of 97.5% in rapid virological response based on hepatitis C virus core antigen and a negative predictive value of 100% in early virological response based on hepatitis C virus core antigen. In conclusion, hepatitis C virus core antigen is comparable to

  10. Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHUO Ming-lei; DUAN Jian-chun; WANG Yu-yan; GUO Qing-zhi; LIU Xu-yi; LIU Ning-hong; WANG Jie; WU Mei-na; ZHAO Jun; Sonya Wei Song; BAI Hua; WANG Shu-hang; YANG Lu; AN Tong-tong; WANG Xin

    2011-01-01

    Background The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy,but its role in cytotoxic chemotherapy is still unknown.Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy.Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC).In this study,we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis.Methods We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department.We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes.Results There were 54 patients with known EGFR mutations and 91 cases of wild types.No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs.31.9%).The median survival time and 1-,2-year survival rates were higher in mutation carriers than wild-types (24months vs.18 months,85.7% vs.65.7% and 43.7% vs.25.9%,P=0.047).Clinical stage (IV vs.Ⅲb),response to the first-line chemotherapy (partial vs.no) and EGFR genotype were independent prognostic factors.Conclusion Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy,but an independent prognostic factor indicating longer survival.

  11. Analysis of Borrelia burgdorferi Genotypes in Patients with Lyme Arthritis: High Frequency of RST 1 Strains in Antibiotic-Refractory Arthritis

    Science.gov (United States)

    Jones, Kathryn L.; McHugh, Gail A.; Glickstein, Lisa J.; Steere, Allen C.

    2009-01-01

    Objective Most of the B. burgdorferi genotypes have been isolated from erythema migrans (EM) skin lesions in patients with Lyme disease; outer-surface protein C (OspC) type K strains, which are 16S-23S rRNA intergenic spacer type 2 (RST 2), are most commonly recovered, but a higher percentage of OspC type A strains (RST 1), the next most common type, are detectable in blood. Our goals were to determine the B. burgdorferi genotypes in the joints of patients with Lyme arthritis. Methods Joint fluid samples from 124 patients seen over a 30-year period were analyzed for OspC types by semi-nested PCR and sequencing, and for RST by nested PCR and RFLP techniques. This information was correlated with clinical outcome. Results OspC and RST genotypes could be determined in 49 of the 124 joint fluid samples (40%). Of the 49 samples, 21 (43%) were OspC type K (RST 2), 11 (22%) were type A (RST 1), and 17 (35%) were distributed among 8 other OspC types and all 3 RSTs. However, among 17 patients who received current antibiotic regimens, all 7 infected with RST 1 strains had antibiotic-refractory arthritis compared with 4 of 6 patients infected with RST 2 strains and only 1 of 4 infected with RST 3 strains (P=0.03). Conclusions Most of the B. burgdorferi genotypes infected the joints of patients with Lyme arthritis, particularly OspC type K (RST 2); and genotype frequencies reflected those in EM skin lesions. However, RST 1 strains were most frequent in patients with antibiotic-refractory arthritis. PMID:19565522

  12. Virology analyses of HCV genotype 4 isolates from patients treated with simeprevir and peginterferon/ribavirin in the Phase III RESTORE study.

    Science.gov (United States)

    Fevery, B; Verbinnen, T; Peeters, M; Janssen, K; Witek, J; Jessner, W; De Meyer, S; Lenz, O

    2017-01-01

    Simeprevir is a hepatitis C virus NS3/4A protease inhibitor. Hepatitis C virus baseline NS3/4A polymorphisms and emerging mutations were characterized in treatment-naїve and treatment-experienced genotype 4-infected patients treated with simeprevir+peginterferon/ribavirin in the RESTORE study. Population sequencing of the NS3/4A region was performed and in vitro simeprevir activity against site-directed mutants or chimeric replicons with patient-derived NS3 protease sequences was assessed in a transient replicon assay. Simeprevir remained active against most (83/91 [91%]) baseline isolates tested in the chimeric replicon assay. Eight baseline isolates reduced simeprevir activity; these carried I132L or D168E substitutions reducing simeprevir median activity by 4.6- and 39-fold, respectively. Six of these eight isolates were from patients achieving sustained virologic response. Baseline NS3 Q80K polymorphism was not observed in the genotype 4-infected patients. Of the 107 simeprevir-treated patients, 37 did not achieve sustained virologic response for any reason. Of the 32 patients who failed treatment and had sequencing information, 28 (88%) had emerging mutations at NS3 positions 80, 122, 155, 156 and/or 168 at time of failure, similar to those in genotype 1. Emerging mutations were mainly D168V and D168E alone or combined with mutations at position 80. In general, isolates obtained at time of failure displayed high-level in vitro resistance to simeprevir (fold change ≥50) in a chimeric replicon assay with a median simeprevir fold change value of 440, consistent with observed mutations. In conclusion, emerging mutations in genotype 4 patients failing simeprevir+peginterferon/ribavirin treatment were similar to those in genotype 1 and conferred high-level resistance to simeprevir.

  13. Evaluation of immunological indices in HIV-infected patients with chronic hepatitis C in Kazakhstan

    Directory of Open Access Journals (Sweden)

    Sarsekeyeva N

    2016-05-01

    Full Text Available Nazgul Sarsekeyeva,1,2 Bakhyt Kosherova3 1Department of Infectious Diseases and Dermatovenerology, Karaganda State Medical University, 2Karaganda Regional Center for the AIDS Prevention and Control, 3Rectorate of Karaganda State Medical University, Karaganda, Kazakhstan Aim: To evaluate immunological indices in HIV-infected patients with chronic hepatitis C (CHC who are injecting drug users. Materials and methods: The study examined 38 patients coinfected with HIV and CHC who were injecting drug users and 36 patients with HIV/CHC who were not injecting drug users. In the study of immune status, the relative and absolute numbers of CD3+, CD4+, CD8+, CD16+, and CD20+ cells were determined by means of flow cytofluorometry of “FACSCount” using monoclonal antibodies of the company Becton Dickinson. The level of circulating immune complexes in blood serum was determined by means of precipitation in polyethylene glycol solution. Results: It was found that T-cell immunodeficiency was developing in patients coinfected with HIV and CHC. T-cell immunodeficiency was characterized by a decrease in the number of T-helpers, mainly for injecting drug users. At the same time, patients coinfected with HIV and CHC experienced markedly elevated levels of circulating immune complexes, mainly among injecting drug users. The evaluation of immunogram indices in injecting drug users coinfected with HIV and CHC, depending on the stage of HIV infection, revealed a greater degree of immune-suppression of T-helper cells in clinical stage III. Conclusion: Our comprehensive immunological study of patients coinfected with HIV and CHC revealed a pronounced dysfunction of the immune system. The comparison of the immune system indices in patients with HIV/CHC showed a more pronounced T-cell suppression in injecting drug users than in patients with HIV/CHC but who were not injecting drug users. Keywords: HIV infection, chronic hepatitis C, immunological indices, injecting drug

  14. KRAS genotypic changes of circulating tumor cells during treatment of patients with metastatic colorectal cancer.

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    Aristea Kalikaki

    Full Text Available INTRODUCTION: Circulating tumor cells (CTCs could represent a non-invasive source of cancer cells used for longitudinal monitoring of the tumoral mutation status throughout the course of the disease. The aims of the present study were to investigate the detection of KRAS mutations in CTCs from patients with metastatic colorectal cancer (mCRC and to compare their mutation status during treatment or disease progression with that of the corresponding primary tumors. MATERIALS AND METHODS: Identification of the seven most common KRAS mutations on codons 12 and 13 was performed by Peptide Nucleic Acid (PNA-based qPCR method. The sensitivity of the assay was determined after isolation of KRAS mutant cancer cells spiked into healthy donors' blood, using the CellSearch Epithelial Cell kit. Consistent detection of KRAS mutations was achieved in samples containing at least 10 tumor cells/7.5 ml of blood. RESULTS: The clinical utility of the assay was assessed in 48 blood samples drawn from 31 patients with mCRC. All patients had PIK3CA and BRAF wild type primary tumors and 14 KRAS mutant tumors. CTCs were detected in 65% of specimens obtained from 74% of patients. KRAS mutation analysis in CTC-enriched specimens showed that 45% and 16.7% of patients with mutant and wild type primary tumors, respectively, had detectable mutations in their CTCs. Assessing KRAS mutations in serial blood samples revealed that individual patient's CTCs exhibited different mutational status of KRAS during treatment. CONCLUSIONS: The current findings support the rationale for using the CTCs as a dynamic source of tumor cells which, by re-evaluating their KRAS mutation status, could predict, perhaps more accurately, the response of mCRC patients to targeted therapy.

  15. Genetic signatures of Mycobacterium tuberculosis Nonthaburi genotype revealed by whole genome analysis of isolates from tuberculous meningitis patients in Thailand.

    Science.gov (United States)

    Coker, Olabisi Oluwabukola; Chaiprasert, Angkana; Ngamphiw, Chumpol; Tongsima, Sissades; Regmi, Sanjib Mani; Clark, Taane G; Ong, Rick Twee Hee; Teo, Yik-Ying; Prammananan, Therdsak; Palittapongarnpim, Prasit

    2016-01-01

    Genome sequencing plays a key role in understanding the genetic diversity of Mycobacterium tuberculosis (M.tb). The genotype-specific character of M. tb contributes to tuberculosis severity and emergence of drug resistance. Strains of M. tb complex can be classified into seven lineages. The Nonthaburi (NB) genotype, belonging to the Indo-Oceanic lineage (lineage 1), has a unique spoligotype and IS6110-RFLP pattern but has not previously undergone a detailed whole genome analysis. In addition, there is not much information available on the whole genome analysis of M. tb isolates from tuberculous meningitis (TBM) patients in public databases. Isolates CSF3053, 46-5069 and 43-13838 of NB genotype were obtained from the cerebrospinal fluids of TBM Thai patients in Siriraj Hospital, Bangkok. The whole genomes were subjected to high throughput sequencing. The sequence data of each isolate were assembled into draft genome. The sequences were also aligned to reference genome, to determine genomic variations. Single nucleotide polymorphisms (SNPs) were obtained and grouped according to the functions of the genes containing them. They were compared with SNPs from 1,601 genomes, representing the seven lineages of M. tb complex, to determine the uniqueness of NB genotype. Susceptibility to first-line, second-line and other antituberculosis drugs were determined and related to the SNPs previously reported in drug-resistant related genes. The assembled genomes have an average size of 4,364,461 bp, 4,154 genes, 48 RNAs and 64 pseudogenes. A 500 base pairs deletion, which includes ppe50, was found in all isolates. RD239, specific for members of Indo Oceanic lineage, and RD147c were identified. A total of 2,202 SNPs were common to the isolates and used to classify the NB strains as members of sublineage 1.2.1. Compared with 1,601 genomes from the seven lineages of M. tb complex, mutation G2342203C was found novel to the isolates in this study. Three mutations (T28910C, C1180580T

  16. Genetic signatures of Mycobacterium tuberculosis Nonthaburi genotype revealed by whole genome analysis of isolates from tuberculous meningitis patients in Thailand

    Directory of Open Access Journals (Sweden)

    Olabisi Oluwabukola Coker

    2016-04-01

    Full Text Available Genome sequencing plays a key role in understanding the genetic diversity of Mycobacterium tuberculosis (M.tb. The genotype-specific character of M. tb contributes to tuberculosis severity and emergence of drug resistance. Strains of M. tb complex can be classified into seven lineages. The Nonthaburi (NB genotype, belonging to the Indo-Oceanic lineage (lineage 1, has a unique spoligotype and IS6110-RFLP pattern but has not previously undergone a detailed whole genome analysis. In addition, there is not much information available on the whole genome analysis of M. tb isolates from tuberculous meningitis (TBM patients in public databases. Isolates CSF3053, 46-5069 and 43-13838 of NB genotype were obtained from the cerebrospinal fluids of TBM Thai patients in Siriraj Hospital, Bangkok. The whole genomes were subjected to high throughput sequencing. The sequence data of each isolate were assembled into draft genome. The sequences were also aligned to reference genome, to determine genomic variations. Single nucleotide polymorphisms (SNPs were obtained and grouped according to the functions of the genes containing them. They were compared with SNPs from 1,601 genomes, representing the seven lineages of M. tb complex, to determine the uniqueness of NB genotype. Susceptibility to first-line, second-line and other antituberculosis drugs were determined and related to the SNPs previously reported in drug-resistant related genes. The assembled genomes have an average size of 4,364,461 bp, 4,154 genes, 48 RNAs and 64 pseudogenes. A 500 base pairs deletion, which includes ppe50, was found in all isolates. RD239, specific for members of Indo Oceanic lineage, and RD147c were identified. A total of 2,202 SNPs were common to the isolates and used to classify the NB strains as members of sublineage 1.2.1. Compared with 1,601 genomes from the seven lineages of M. tb complex, mutation G2342203C was found novel to the isolates in this study. Three mutations (T28910

  17. Impact of ribavirin dosage in chronic hepatitis C patients treated with simeprevir, pegylated interferon plus ribavirin combination therapy.

    Science.gov (United States)

    Tahata, Yuki; Hiramatsu, Naoki; Oze, Tsugiko; Urabe, Ayako; Morishita, Naoki; Yamada, Ryoko; Yakushijin, Takayuki; Hosui, Atsushi; Oshita, Masahide; Kaneko, Akira; Hagiwara, Hideki; Mita, Eiji; Ito, Toshifumi; Yamada, Yukinori; Inada, Masami; Katayama, Kazuhiro; Tamura, Shinji; Imai, Yasuharu; Hikita, Hayato; Sakamori, Ryotaro; Yoshida, Yuichi; Tatsumi, Tomohide; Hayashi, Norio; Takehara, Tetsuo

    2016-10-01

    The factors associated with sustained virologic response (SVR) in chronic hepatitis C (CH-C) genotype 1 patients treated with simeprevir (SMV), pegylated interferon (Peg-IFN) plus ribavirin (RBV) triple therapy have not been fully investigated. Two hundred and twenty-nine treatment-naïve CH-C patients treated with SMV triple therapy were enrolled in this study. The overall SVR rate was 87% in per-protocol analysis. In multivariate analysis, the interleukin (IL) 28B genotype (rs8099917, TT vs. non-TT, odds ratio [OR]: 0.044, P = 0.001) and RBV dose (< 10/10-12/ ≥ 12 mg/kg/day, OR: 4.513, P = 0.041) were significant factors associated with SVR. In patients with the IL28B non-TT genotype, RBV dose affected SVR dose-dependently in stratified analysis of RBV dose (P = 0.015); it was 44% (8/18) for patients administered <10 mg/kg/day of RBV, 78% (14/18) for those administered 10-12 mg/kg/day of RBV, and 100% (3/3) for those administered ≥12 mg/kg/day of RBV, whereas in patients with the IL28B TT genotype, a significant correlation between SVR and RBV dose was not observed (P = 0.229). Regarding RBV dose reduction of less than 10 mg/kg/day, the inosine triphosphate pyrophosphatase (ITPA) genotype (rs1127354, CC vs. non-CC, OR: 0.239, P = 0.003) and age (by 1 y.o., OR: 1.084, P = 0.002) were significant independent factors. RBV dosage affected SVR dose-dependently in patients with the IL28B non-TT genotype treated with SMV triple therapy. Special attention to anemia progression and RBV dosage should be paid to aged patients with the ITPA CC genotype. J. Med. Virol. 88:1776-1784, 2016. © 2016 Wiley Periodicals, Inc.

  18. HLA-DRB1 ALLELES GENOTYPING IN PATIENTS WITH RHEUMATOID ARTHRITIS IN CHINESE

    Institute of Scientific and Technical Information of China (English)

    赵岩; 董怡; 朱席林; 邱长春

    1996-01-01

    Objective. To explore the role of HLA-DRB1 genes in the development of rheumatoid arthritis(RA) and the correlations between HLA-DR alleles and clinical manifestations of patients with RA.Methods. 86 patients with rheumatoid arthritis and 106 race matched controls were studied in whom HLA-DR typing was perfomed by the method of DNA amplification with sequence-specific primers(PCR-SSP). The subtypes of HLA-DR4 were determined by the method of hybridization of PCR products with sequence-specific oligonucletides(PCR SSO). The absence or presence of the patients.Results.Compared with controls,an increased gene frequency of HLA-DR4(48.8% vs 17.9%,P<0.001) and a decreased frequency of HLA-DR7(16.3% vs 27.4%,P=0.06) were found.The DRB1 0405 account for 61.9% of DR4+RA patients with respect to age,sex,duration of disease,rheumatoid factor(RF),extra-articular manifestations including secondary Sjogren's syndrome.According to the wrisr X-ray stage,the patlents of DR4+were more severe than that of DR4-P(P<0.05).Conclusion.HLA-DR4 and DR4 subtype of DRB1 0405 are related to the development of RA in Chinese.HLA-DR4 can be a useful prognosric marker in the patients with RA.

  19. First baseline of circulating genotypic lineages of Mycobacterium tuberculosis in patients from the brazilian borders with Argentina and Paraguay.

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    Luzia Neri C Machado

    Full Text Available BACKGROUND: At the triple border Brazil/Paraguay/Argentina there is easy mobility from one city to another for economic and tourism activities. This constant and fast population mobility is mainly to visit Iguazu Falls, in the Iguazu River, on the border of the Brazilian state of Paraná and the Argentina. As the incidence of tuberculosis is high in this setting, our study aimed to establish a first baseline of circulating genotypic lineages of Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: This study included 120 patients from 10 cities in southwestern Paraná, Brazil with pulmonary symptoms, from July 2009 to July 2011. Information about sex, age, clinical features and address was collected by reviewing the national tuberculosis notification database. Of these, 96 (80% isolates were identified as M. tuberculosis and 22 (22.9% were drug resistant (20, 20.8% INH mono-resistant and 2, 2.1% multidrug-resistant. All isolates were subjected to genotyping by Spoligotyping and MIRU-VNTR typing. The distribution of the isolates analyzed by spoligotyping revealed 30 distinct patterns. The four mainly detected clades were Latin American and Mediterranean (LAM, ill-defined T, Haarlem (H and S. The MIRU-VNTR showed 85 distinct patterns. Spoligotyping combined to MIRU-VNTR allowed 90 distinct patterns. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated that there is significant molecular diversity in circulating M. tuberculosis, with predominance of the LAM and T clades in cities of southwestern Paraná, Brazil, bordering Argentina and Paraguay.

  20. Prevalence of Helicobacter pylori cagA genotype among dyspeptic patients in Southern Thailand

    Institute of Scientific and Technical Information of China (English)

    Sueptrakool Wisessombat; Chatruthai Meethai

    2014-01-01

    Objective: To investigate the prevalence of Helicobacter pylori (H. pylori) infection in dyspepsia patients and its relation to virulence factor cagA gene. Methods: In total, 110 gastric biopsies from dyspeptic patients were comparatively studied using rapid urease test and multiplex polymerase chain reaction (PCR). Results: Multiplex PCR detected three genes of 16S rRNA, cagA, and ureC. H. pylori was detected in 14 gastric biopsies (13%). Significantly higher numbers of female were infected. Furthermore,cag A gene was found in all H. pylori-positive specimens. In addition, the result indicated that the multiplex PCR with annealing temperature at 57 oC was able to effectively amplify specific products. Conclusions:The results confirmed high prevalence of cagA gene in H. pylori among dyspeptic patients in Southern Thailand.

  1. Molecular Characterization of Acanthamoeba spp. Occurring in Water Bodies and Patients in Poland and Redefinition of Polish T16 Genotype.

    Science.gov (United States)

    Adamska, Małgorzata

    2016-01-01

    Acanthamoeba genus is divided into 20 genotypes (T1-T20) on the basis of the gene encoding 18S rRNA sequence. Using of at least 2 kbp gene fragments is strongly recommended to identify new genotypes and 5% difference is commonly used as a criterion of new genotypes, however, this value is questionable. In this paper, Polish Acanthamoeba strains described earlier on the basis of ~850 bp Ami fragment of 18S rRNA gene as T4, T11 and a new T16 genotype, have been analyzed using near-complete sequence of the gene. This analysis was needed because the Ami fragment does not reveal full variability within 18S rRNA gene. Phylogenetic analysis based on Ami fragment is biased by artifacts in the construction of the tree, so the fragment should not be used for identification of new putative Acanthamoeba genotypes. The analysis confirmed that the Polish sequences represent T4 and T11 genotypes and that the strains described earlier as T16 genotype are in fact a new subgroup of the T20 genotype and that this genotype should be divided into two subgroups: T20a (two strains described by [J. Eukaryot. Microbiol. 62 (2015) 69]) and T20b (11 Polish strains described in this study). The T20b subgroup was isolated from both clinical samples and water bodies used by people as bathing places and there is a risk of infection for humans during contact with water.

  2. Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype).

    Science.gov (United States)

    Hannemann, A; Rees, D C; Tewari, S; Gibson, J S

    2015-11-01

    Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

  3. Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response

    DEFF Research Database (Denmark)

    Dalgard, Olav; Bjøro, Kristian; Larsen, Helmer Ring

    2008-01-01

    A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428...

  4. Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection: A prospective, real-life, observational study

    Institute of Scientific and Technical Information of China (English)

    Patrice Cacoub; Denis Ouzan; Pascal Melin; Jean-Philippe Lang; Michel Rotily; Thierry Fontanges; Marina Varastet; Michel Chousterman; Patrick Marcellin

    2008-01-01

    AIM: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C, as there are few adherence data in genotype 2/3 infection, even from randomized trials. METHODS: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin. There was no intervention. Adherence was self-reported over the past 4 wk (peg-interferon) or 7 d (ribavirin). Adherence to bitherapy was defined as adherence to the two drugs for≥20 wk. SVR was defined as undetectable RNA≥12 wk after the end of treatment. RESULTS: 370/674 patients received education during the first 3 mo of treatment. After 6 mo, adherence to bitherapy was higher in educated patients (61% vs 47%, P=0.01). Adherence to peg-interferon was 78% vs 69% (P=0.06). Adherence to ribavirin was 70% vs 56% (P=0.006). The SVR (77% vs 70%, P = 0.05) and relapse (10% w 16%, P = 0.09) rates tended to be improved. After adjustment for baseline differences, education improved adherence [Odds ratio (OR) 1.58, P=0.04] but not the SVR (OR 1.54, P=0.06). CONCLUSION: In genotype 2/3 patients, therapeutic education helped maintain real-life adherence to bitherapy.

  5. Genotype-phenotype relationship in patients with mutations in thyroid hormone transporter MCT8

    NARCIS (Netherlands)

    J.A. Jansen (John); E.C.H. Friesema (Edith); M.H.A. Kester (Monique); C.E. Schwartz; T.J. Visser (Theo)

    2008-01-01

    textabstractLoss-of-function mutations in thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to severe X-linked psychomotor retardation and elevated serum T3levels. Most patients, for example those with mutations V235M, S448X, insI189, or delF230, cannot stand, walk, or speak. Pat

  6. Analysis of phenotype, enzyme activity and genotype of Chinese patients with POMT1 mutation.

    Science.gov (United States)

    Yang, Haipo; Manya, Hiroshi; Kobayashi, Kazuhiro; Jiao, Hui; Fu, Xiaona; Xiao, Jiangxi; Li, Xiaoqing; Wang, Jingmin; Jiang, Yuwu; Toda, Tatsushi; Endo, Tamao; Wu, Xiru; Xiong, Hui

    2016-08-01

    Protein O-mannosyltransferase 1 (POMT1) is a glycosyltransferase involved in α-dystroglycan glycosylation. POMT1 mutations cause a wide spectrum of clinical conditions from Walker-Warburg syndrome (WWS), which involves muscle, eye and brain abnormalities, to mild forms of limb-girdle muscular dystrophy with mental retardation. We aimed to elucidate the impact of different POMT1 mutations on the clinical phenotype. We report five Chinese patients with POMT1 mutations: one had a typical clinical manifestation of WWS, and the other four were diagnosed with congenital muscular dystrophy with mental retardation of varying severity. We analyzed the influence of the POMT1 mutations on POMT activity by assaying the patients' muscles and cultured skin fibroblasts. We demonstrated different levels of decreased POMT activity that correlated highly with decreased α-dystroglycan glycosylation. Our results suggest that POMT activity is inversely proportional to clinical severity, and demonstrate that skin fibroblasts can be used for differential diagnosis of patients with α-dystroglycanopathies. We have provided clinical, histological, enzymatic and genetic evidence of POMT1 involvement in five unrelated Chinese patients.

  7. Phenotype and genotype in 17 patients with Goltz-Gorlin syndrome

    NARCIS (Netherlands)

    Maas, S.M.; Lombardi, P.M.; van Essen, A.J.; Wakeling, E.L.; Castle, B.; Temple, I.K.; Kumar, V.K.A.; Writzl, K.; Hennekam, R.C.M.

    2009-01-01

    Background: Goltz-Gorlin syndrome or focal dermal hypoplasia is a highly variable, X-linked dominant syndrome with abnormalities of ectodermal and mesodermal origin. In 2007, mutations in the PORCN gene were found to be causative in Goltz-Gorlin syndrome. Method: A series of 17 patients with Goltz-G

  8. Phenotype and genotype in 17 patients with Goltz-Gorlin syndrome

    NARCIS (Netherlands)

    Maas, S. M.; Lombardi, M. P.; van Essen, A. J.; Wakeling, E. L.; Castle, B.; Temple, I. K.; Kumar, V. K. A.; Writzl, K.; Hennekam, Raoul C. M.

    2009-01-01

    Background: Goltz-Gorlin syndrome or focal dermal hypoplasia is a highly variable, X-linked dominant syndrome with abnormalities of ectodermal and mesodermal origin. In 2007, mutations in the PORCN gene were found to be causative in Goltz-Gorlin syndrome. Method: A series of 17 patients with Goltz-G

  9. Effect of ezetimibe coadministered with statins in genotype-confirmed heterozygous FH patients.

    Science.gov (United States)

    Pisciotta, Livia; Fasano, Tommaso; Bellocchio, Antonella; Bocchi, Letizia; Sallo, Raffaella; Fresa, Raffaele; Colangeli, Isabella; Cantafora, Alfredo; Calandra, Sebastiano; Bertolini, Stefano

    2007-10-01

    We investigated the effect of statins and statins plus ezetimibe in 65 FH heterozygotes carrying LDLR-defective or LDLR-negative mutations as well as the effect of ezetimibe monotherapy in 50 hypercholesterolemic (HCH) patients intolerant to statins. PCSK9 and NPC1L1 genes were analysed to assess the role of genetic variants in response to therapy. In FH patients combined therapy reduced LDL-C by 57%, irrespective of the type of LDLR mutation. The additional decrease of plasma LDL-C induced by ezetimibe showed wide inter-individual variability (from -39% to -4.7%) and was negatively correlated with percent LDL-C decrease due to statin alone (r=-0.713, PG polymorphism (L272L) in hyper-responders, an observation confirmed also in FH patients hyper-responders to ezetimibe. In both FH and HCH patients, the G allele carriers tended to have a higher LDL-C reduction in response to ezetimibe. These observations suggest that in FH heterozygotes LDL-C reduction following combined therapy reflects a complex interplay between hepatic synthesis and intestinal absorption of cholesterol.

  10. Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections.

    Directory of Open Access Journals (Sweden)

    Maxime Levert

    Full Text Available Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients or by members of a single clone that exhibit micro-heterogeneity (11 patients; both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC. We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious

  11. Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections.

    Science.gov (United States)

    Levert, Maxime; Zamfir, Oana; Clermont, Olivier; Bouvet, Odile; Lespinats, Sylvain; Hipeaux, Marie Claire; Branger, Catherine; Picard, Bertrand; Saint-Ruf, Claude; Norel, Françoise; Balliau, Thierry; Zivy, Michel; Le Nagard, Hervé; Cruveiller, Stéphane; Cruvellier, Stéphane; Chane-Woon-Ming, Béatrice; Nilsson, Susanna; Gudelj, Ivana; Phan, Katherine; Ferenci, Thomas; Tenaillon, Olivier; Denamur, Erick

    2010-09-30

    Although polymicrobial infections, caused by combinations of viruses, bacteria, fungi and parasites, are being recognised with increasing frequency, little is known about the occurrence of within-species diversity in bacterial infections and the molecular and evolutionary bases of this diversity. We used multiple approaches to study the genomic and phenotypic diversity among 226 Escherichia coli isolates from deep and closed visceral infections occurring in 19 patients. We observed genomic variability among isolates from the same site within 11 patients. This diversity was of two types, as patients were infected either by several distinct E. coli clones (4 patients) or by members of a single clone that exhibit micro-heterogeneity (11 patients); both types of diversity were present in 4 patients. A surprisingly wide continuum of antibiotic resistance, outer membrane permeability, growth rate, stress resistance, red dry and rough morphotype characteristics and virulence properties were present within the isolates of single clones in 8 of the 11 patients showing genomic micro-heterogeneity. Many of the observed phenotypic differences within clones affected the trade-off between self-preservation and nutritional competence (SPANC). We showed in 3 patients that this phenotypic variability was associated with distinct levels of RpoS in co-existing isolates. Genome mutational analysis and global proteomic comparisons in isolates from a patient revealed a star-like relationship of changes amongst clonally diverging isolates. A mathematical model demonstrated that multiple genotypes with distinct RpoS levels can co-exist as a result of the SPANC trade-off. In the cases involving infection by a single clone, we present several lines of evidence to suggest diversification during the infectious process rather than an infection by multiple isolates exhibiting a micro-heterogeneity. Our results suggest that bacteria are subject to trade-offs during an infectious process and that

  12. Genotyping analysis for the 46 C/T polymorphism of coagulation factor XII and the involvement of factor XII activity in patients with recurrent pregnancy loss.

    Directory of Open Access Journals (Sweden)

    Eriko Asano

    Full Text Available BACKGROUND: Established causes of recurrent pregnancy loss (RPL include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations and abnormal embryonic karyotype. A systematic review concluded that coagulation factor XII (FXII deficiency was associated with RPL. However, it could not be established whether the 46 C/T SNP of FXII or low activity of FXII was a risk factor for RPL, because of the small sample size. METHODS AND FINDINGS: We conducted a cross-sectional and cohort study in 279 patients with two or more unexplained consecutive pregnancy losses and 100 fertile women. The association between the lupus anticoagulant (LA activity and FXII activity was examined. The frequency of the CC, CT and TT genotypes and the FXII activity were also compared between the patients and controls. Subsequent miscarriage rates among the CC, CT, TT genotypes and according to the FXII activity was examined. LA was associated with reduced FXII activity. The CT, but not the TT, genotype was confirmed to be a risk factor for RPL in the cross-sectional study using multivariate logistic regression analysis (OR, 2.8; 95% CI, 1.37-5.85. The plasma FXII activity in the patients was similar to that in the controls. Neither low FXII activity nor the CT genotype predicted the subsequent pregnancy outcome in the cohort study. On the other hand, and intermediate FXII activity level of 85-101% was predictive of subsequent miscarriage. CONCLUSIONS: Low FXII activity was not associated with RPL. The FXII gene was found to be one of the significant susceptibility genes for RPL, similar to the FV Leiden mutation. However, the clinical influence of the CT genotype might be relatively small, because the presence/absence of this genotype did not have any predictive value for the subsequent pregnancy outcome. This was the first study indicating the influence of FXII 46C/T on further pregnancy outcomes.

  13. Genotyping, levels of expression and physical status of human papilloma virus in oropharyngeal squamous cell carcinoma among Colombian patients.

    Science.gov (United States)

    Erira, Alveiro; Motta, Leidy Angélica; Chala, Andrés; Moreno, Andrey; Gamboa, Fredy; García, Dabeiba Adriana

    2015-10-23

    One of the risk factors for squamous cell oropharyngeal carcinoma is infection with the human papilloma virus (HPV), with prevalences that vary depending on the geographical region.  To identify the most frequent HPV viral types in oropharyngeal cancer, the levels of expression and the physical condition of the viral genome.  Forty-six patients were included in the study from among those attending head and neck surgical services in the cities of Bogotá, Manizales and Bucaramanga. In the histopathological report all study samples were characterized as oropharyngeal squamous cell carcinoma. DNA extraction was subsequently performed for HPV genotyping and to determine the physical state of the viral genome, as well as RNA to determine viral transcripts using real-time PCR.  HPV prevalence in tumors was 21.74% (n=10) and the most common viral type was HPV-16 (nine cases). Viral expression for HPV-16 was low (one of 11 copies) and the predominant physical state of the virus was mixed (eight cases), with disruption observed at the E1 - E2 binding site (2525 - 3720 nucleotides).  The prevalence of HPV associated with oropharyngeal carcinoma among the Colombian study population was 21.7%, which is relatively low. The most frequent viral type was HPV-16, found in a mixed form and with low expression of E7, possibly indicating a poor prognosis for these patients.

  14. Recent insights into genotype-phenotype relationships in patients with Rett syndrome using a fine grain scale.

    Science.gov (United States)

    Fabio, Rosa Angela; Colombo, Barbara; Russo, Silvia; Cogliati, Francesca; Masciadri, Maura; Foglia, Silvia; Antonietti, Alessandro; Tavian, Daniela

    2014-11-01

    Mutations in MECP2 gene cause Rett syndrome (RTT), a neurodevelopmental disorder affecting around 1 in 10,000 female births. The clinical picture of RTT appears quite heterogeneous for each single feature. Mutations in MECP2 gene have been associated with the onset of RTT. The most known gene function consists of transcriptional repression of specific target genes, mainly by the binding of its methyl binding domain (MBD) to methylated CpG nucleotides and recruiting co-repressors and histone deacetylase binding to DNA by its transcription repressor domain (TRD). This study aimed at evaluating a cohort of 114 Rett syndrome (RTT) patients with a detailed scale measuring the different kinds of impairments produced by the syndrome. The sample included relatively large subsets of the most frequent mutations, so that genotype-phenotype correlations could be tested. Results revealed that frequent missense mutations showed a specific profile in different areas of impairment. The R306C mutation, considered as producing mild impairment, was associated to a moderate phenotype in which behavioural characteristics were mainly affected. A notable difference emerged by comparing mutations truncating the protein before and after the nuclear localization signal; such a difference concerned prevalently the motor-functional and autonomy skills of the patients, affecting the management of everyday activities.

  15. Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Kjeldsen, A D; Møller, T R; Brusgaard, K

    2005-01-01

    BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically...... heterogeneous disorder involving at least two loci; HHT 1 mapping to chromosome 9 q 34.1 (ENG) and HHT 2 mapping to chromosome 12 q 31 (ALK-1). OBJECTIVE: To evaluate and describe the diversity of clinical manifestations in a Danish population of HHT patients with known HHT 1 or HHT 2 subtype. DESIGN......: Prospective clinical examination with genetic evaluation and follow-up. SETTING: Investigation centre was Odense University Hospital. All HHT patients in the County of Fyn were included. METHODS: HHT family members were invited to a clinical examination including registration of HHT manifestations, screening...

  16. Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation

    Institute of Scientific and Technical Information of China (English)

    Cathy Lu; Alistair Waugh; Robert J Bailey; Raeleen Cherry; Levinus A Dieleman; Leah Gramlich; Kata Matic

    2012-01-01

    AIM:To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission.METHODS:Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response,were identified by review of an electronic database and charts.Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI)< 150] during follow-up visits based on physician global assessments.A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI > 220) and a therapeutic intervention with CD medication(s),or a hospitalization with complications related to active CD.Genetic analyses were performed on samples from 14 patients (n =6 who had a sustained long term remission after stopping infliximab,n =8 who rapidly relapsed after stopping infliximab).Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W,G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5)polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group.RESULTS:Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects.There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W,G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab.Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission,while two-thirds relapsed rapidly.There was a marked

  17. Difference in Antibody Responses to Mycobacterium tuberculosis Antigens in Japanese Tuberculosis Patients Infected with the Beijing/Non-Beijing Genotype

    Science.gov (United States)

    Zhao, Jingge; Okumura, Masao; Yanai, Hideki; Matsumoto, Makoto; Mizuno, Kazue; Ono, Kenji; Oda, Tetsuya; Ashino, Yugo; Matsuba, Takashi; Yoshiyama, Takashi; Suzuki, Yasuhiko

    2017-01-01

    The Beijing genotype Mycobacterium tuberculosis (MTB), notorious for its virulence and predisposition to relapse, could be identified by spoligotyping based on genetic heterogeneity. The plasma samples from 20 cases of Beijing and 16 cases of non-Beijing MTB infected individuals and 24 healthy controls (HCs) were collected, and antibodies against 11 antigens (Rv0679c142Asn, Rv0679c142Lys, Ag85B, Ag85A, ARC, TDM-M, TDM-K, HBHA, MDP-1, LAM, and TBGL) were measured by ELISA. Compared to the HCs, the MTB infected subjects showed higher titers of anti-Ag85B IgG (positivity 58.2%) and anti-ACR IgG (positivity 48.2%). Of note, anti-ACR IgG showed higher titer in Beijing MTB infected tuberculosis (TB) patients than in HC (Kruskal–Wallis test, p < 0.05), while the levels of anti-Ag85B, anti-TBGL, anti-TDM-K, and anti-TDM-M IgG were higher in non-Beijing TB patients than in HC. Moreover, anti-Ag85B IgG showed higher response in non-Beijing TB patients than in Beijing TB patients (p < 0.05; sensitivity, 76.9% versus 44.4%). The sensitivity and specificity analysis showed that 78.8% Beijing infected individuals were negative in anti-TBGL-IgG or/and anti-Ag85B-IgG, while 75.0% of those were positive in anti-TBGL-IgA or/and anti-ACR-IgG tests. These results indicate the possibility of developing antibody-based test to identify Beijing MTB. PMID:28182078

  18. Phenotypic and genotypic characterization of Stenotrophomonas maltophilia isolates from patients with cystic fibrosis: genome diversity, biofilm formation, and virulence.

    Science.gov (United States)

    Pompilio, Arianna; Pomponio, Stefano; Crocetta, Valentina; Gherardi, Giovanni; Verginelli, Fabio; Fiscarelli, Ersilia; Dicuonzo, Giordano; Savini, Vincenzo; D'Antonio, Domenico; Di Bonaventura, Giovanni

    2011-07-05

    Stenotrophomonas maltophilia is emerging as one of the most frequently found bacteria in cystic fibrosis (CF) patients. In the present study, phenotypic and genotypic traits of a set of 98 isolates of S. maltophilia obtained from clinical (CF and non-CF patients) and environmental sources were comparatively evaluated. S. maltophilia exhibited a high level of genomic diversity in both CF and non-CF group, thus possibly allowing this bacterium to expand its pathogenic potentials. Strains sharing the same pulsotype infected different patients, thus likely indicating the occurrence of clonal spread or acquisition by a common source. CF isolates differed greatly in some phenotypic traits among each other and also when compared with non-CF isolates, demonstrating increased mean generation time and susceptibility to oxidative stress, but reduced ability in forming biofilm. Furthermore, in CF isolates flagella- and type IV pili-based motilities were critical for biofilm development, although not required for its initiation. Sequential isogenic strains isolated from the same CF patient displayed heterogeneity in biofilm and other phenotypic traits during the course of chronic infection. CF and non-CF isolates showed comparable virulence in a mouse model of lung infection. Overall, the phenotypic differences observed between CF and non-CF isolates may imply different selective conditions and persistence (adaptation) mechanisms in a hostile and heterogeneous environment such as CF lung. Molecular elucidation of these mechanisms will be essential to better understand the selective adaptation in CF airways in order to design improved strategies useful to counteract and eradicate S. maltophilia infection.

  19. Phenotype and genotype of deaf patients with combined genomic and mitochondrial inheritance models.

    Science.gov (United States)

    Huang, Shasha; Wang, Guojian; Jiang, Yi; Yuan, Yongyi; Han, Dongyi; Song, Yueshuai; Dai, Pu

    2013-11-01

    In most studies, sensorineural hearing loss is reported as a single-gene disease with autosomal dominant or autosomal recessive or with X-linked or maternal inheritance. It is uncommon that the hearing impairment is caused by a combined inheritance model including genomic and mitochondrial models. Here, we report six patients with sensorineural hearing loss caused by co-existing mutations in GJB2 or SLC26A4 and the mitochondrial gene. And there was no significant difference in hearing phenotypes between the six patients and the controls. The results indicate the complicated genetic etiology of, and may impact the diagnostic strategy for, hereditary hearing impairment. All patient siblings will carry mitochondrial DNA A1555G or C1494T mutations, and 25% of siblings may carry the same homozygous or compound heterozygote mutations in GJB2 or SLC26A4. Although this combined inheritance is not common in the Chinese deaf population (0.10%), our findings will have great impact in genetic counseling and risk prediction for deafness.

  20. Effect of N-acetylcysteine in COPD patients with different microsomal epoxide hydrolase genotypes

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    Zhang JQ

    2015-05-01

    Full Text Available Jian-Qing Zhang,1 Jia-Qiang Zhang,1 Hua Liu,2 Zhi-Huan Zhao,1 Li-Zhou Fang,1 Ling Liu,1 Wei-Ping Fu,1 Jing-Kui Shu,1 Jia-Gang Feng,1 Lu-Ming Dai1 1Department of Respiratory Critical Care Medicine, 2Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China Background: The role of the antioxidant N-acetylcysteine (NAC in the treatment of chronic obstructive pulmonary disease (COPD has not been clarified as yet. In early studies, we found that the proportion of smokers with COPD having extremely slow/slow microsomal epoxide hydrolase (EPHX1 enzyme activity is significantly higher than that in healthy smokers. The purpose of this study was to evaluate whether different EPHX1 enzyme activity is related to differential therapeutic effects of treatment with NAC in COPD.Methods: A total of 219 patients with COPD were randomly allocated to an extremely slow/slow EPHX1 enzyme activity group (n=157 or a fast/normal EPHX1 enzyme activity group (n=62 according to their EPHX1 enzyme activity. Both groups were treated with NAC 600 mg twice daily for one year. The main study parameters, including forced expiratory volume in one second (FEV1, St George’s Respiratory Questionnaire (SGRQ, and yearly exacerbation rate, were measured at baseline and at 6-month intervals for one year.Results: Both FEV1 and SGRQ symptom scores were improved after treatment with NAC in the slow activity group when compared with the fast activity group. Further, changes in FEV1 and SGRQ symptom score in patients with mild-to-moderate COPD were more significant than those in patients with severe-to-very severe COPD. The yearly exacerbation rates were reduced in both groups, but the reduction in the slow activity group was significantly lower than in the fast activity group.Conclusion: NAC treatment in COPD patients with extremely slow/slow EPHX1 enzyme activity improves FEV1 and the SGRQ symptom score, especially

  1. High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in Singapore.

    Science.gov (United States)

    Tan, Louise Soo Yee; Fredrik, Petersson; Ker, Liang; Yu, Feng Gang; Wang, De Yun; Goh, Boon Cher; Loh, Kwok Seng; Lim, Chwee Ming

    2016-12-27

    Human papillomavirus (HPV), especially HPV16 genotype, is associated with oropharyngeal squamous cell carcinoma (OPSCC). We aim to determine the prevalence and characterize the high-risk (HR)-HPV genotypes in head and neck SCC (HNSCC) in a South-East Asian multi-ethnic society in Singapore and examine its prognostic significance.159 HNSCC archival tissue samples were retrieved and tumour DNA was screened for 18 HR-HPV genotypes using a PCR-based assay (Qiagen, digene HPV genotyping RH test). P16 protein overexpression was identified using immunohistochemistry (IHC). Statistical correlation between clinical outcomes were performed between HPV-positive and negative HNSCC patients.Six HR-HPVs (HPV16, 18, 31, 45, 56, 68) were detected in 90.6% of HNSCC; and 79.9% had multiple HPV genotypes detected. HPV31 and HPV45 were the most prevalent (79.2% and 87.4%, respectively); and HPV16 was predominantly found in OPSCC (p HPV-DNA PCR assay yielded a high sensitivity (96%) but low specificity (11%) when compared to p16 immunohistochemistry as the reference standard.P16-positive HNSCC was predominantly observed in OPSCC (73.7%; p = 0.005); and p16-positive OPSCC exhibited improved overall survival compared to p16-negative OPSCC (p = 0.022). Similarly, smoking and alcohol consumption were poor prognostic factors of overall survival (p = 0.007; p = 0.01) in OPSCC patients.HR-HPVs were identified in 90.6% of HNSCC patients using the HPV-DNA PCR assay. This test had a poor specificity when compared to p16 IHC; making it an unreliable detection technique in selecting patients for radiation dose de-escalation treatment protocol. P16-positive tumor was predominantly found in the oropharynx these patients demonstrated better overall survival than those with p16-negative OPSCC.

  2. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients

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    Alessandro Grasso

    2015-01-01

    Full Text Available Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033 and 0.048, resp. in patients who achieved an early viral load decay (EVR, a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

  3. Lack of correlation between UGT1A1*6, *28 genotypes, and plasma raltegravir concentrations in Japanese HIV-1-infected patients

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    M Takahashi

    2012-11-01

    Full Text Available Background: Raltegravir is metabolized by glucuronidation via UGT1A1. Among the genetic polymorphisms of UGT1A1, the *6, *27 and *28 alleles are associated with reduced levels of UGT1A1. In particular, the *28 allele accounts for most of the UGT1A1 polymorphisms, and the level of UGT1A1 activity has been the focus of most studies. On the other hand, among Asians, the *6 and *27 alleles are more commonly found in comparison with white populations. In this study, we aimed to clarify the contribution of UGT1A1 polymorphisms (*6, *27 to plasma raltegravir concentrations in Japanese HIV-1-infected patients.Materials & Methods: We analyzed the presence of genotypic variants (*6, *27 and *28 among the 74 patients recruited at the National Hospital Organization Nagoya Medical Center. Genotyping of *6 and *27 in UGT1A1 was performed using the TaqMan drug metabolism genotyping assay. Genotyping of *28 in UGT1A1 was performed using the primers described by Ehmer et al. Plasma raltegravir concentrations were determined by a LC-MS method. Results: Among the 74 patients, the UGT1A1 genotype in 3 patients (two male, one female was *6 homozygote. Heterozygous variants were found in 20 patients for *6, and in 14 patients for *28, while all of the patients were found to carry wild-type sequences at the position corresponding to the *27 allele. The male *6 homozygote patient had modestly higher plasma raltegravir concentration (0.53 µg/ml than other patients who were wild type (0.12 µg/ml or heterozygous (0.16 µg/ml for the *6 polymorphism. The other two UGT1A1*6 homozygote patients had a lower plasma raltegravir concentration (0.03 and 0.05 µg/ml. On the other hand, plasma raltegravir concentrations were 0.12 µg/ml (*6−/− *28−/−; n=37, 0.11 µg/ml (*6−/− *28−/+; n=14, 0.16 µg/ml (*6−/+ *28−/−; n=20. There were no statistically significant differences in the plasma raltegravir concentrations between patients carrying wild-type alleles and

  4. Validation of celiac disease diagnoses recorded in the Danish National Patient Register using duodenal biopsies, celiac disease-specific antibodies, and human leukocyte-antigen genotypes

    DEFF Research Database (Denmark)

    Sander, Stine Dydensborg; Stordal, Ketil; Hansen, Tine Plato

    2016-01-01

    PURPOSE: The purpose of this study was to validate the celiac disease diagnoses recorded in the Danish National Patient Register. To validate the diagnoses, we used information on duodenal biopsies from a national register of pathology reports (the Patobank) and information on celiac disease......-specific antibodies and human leukocyte antigen (HLA) genotypes obtained from patient medical records. PATIENTS AND METHODS: We included all the children who were born from 1995 to 2012 and who were registered as having celiac disease in the Danish National Patient Register. We reviewed all the pathology reports...... on duodenal biopsies in the Patobank and the information in the medical records on celiac disease-specific antibodies (ie, anti-tissue transglutaminase 2 IgA and IgG, endomysial antibodies IgA, and anti-deamidated gliadin peptide IgG) and HLA genotypes. RESULTS: We identified 2,247 children who were...

  5. Heterogeneity of cag genotypes of Helicobacter pylori in the esophageal mucosa of dyspeptic patients and its relation to histopathological outcomes

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    Monica Contreras

    2014-09-01

    Conclusions: H. pylori may coexist in similar proportions without dominance of one cag genotype, suggesting a heterogeneous distribution in the esophagus. The cagE and virB11 genes can be used as markers of cag-PAI in the esophagus. The single cag-PAI genotype in both mucosae confers an increased risk of developing histological damage.

  6. Fatal Cryptococcus gattii genotype VGI infection in an HIV-positive patient in Barranquilla, Colombia

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    María Clara Noguera

    Full Text Available ABSTRACT Cryptococcosis is a major invasive fungal disease related worldwide with the AIDS population. New reports of HIV/AIDS cases to the national public health surveillance system (SIVIGILA in Colombia have shown that there is a growing community at risk of contracting cryptococcosis throughout the country who do not have access to ART. Even though the most prevalent species Cryptococcus neoformans is mainly associated with the HIV population, we report a fatal case of cryptococcosis in an AIDS patient in Barranquilla, associated with Cryptococcus gattii VGI, isolated from blood culture.

  7. Fatal Cryptococcus gattii genotype VGI infection in an HIV-positive patient in Barranquilla, Colombia.

    Science.gov (United States)

    Noguera, María Clara; Escandón, Patricia; Castañeda, Elizabeth

    2017-06-01

    Cryptococcosis is a major invasive fungal disease related worldwide with the AIDS population. New reports of HIV/AIDS cases to the national public health surveillance system (SIVIGILA) in Colombia have shown that there is a growing community at risk of contracting cryptococcosis throughout the country who do not have access to ART. Even though the most prevalent species Cryptococcus neoformans is mainly associated with the HIV population, we report a fatal case of cryptococcosis in an AIDS patient in Barranquilla, associated with Cryptococcus gattii VGI, isolated from blood culture.

  8. Phenotypic and Genotypic Analysis of Multidrug-Resistant Mycobacterium tuberculosis Isolates from Sudanese Patients

    Science.gov (United States)

    Salih, Mohamed Ahmed; Ali, Manasik; EL-Zaki, Salah-Eldin; Abuzeid, Nadir; Elgadi, Zeinab Abubaker Mohammed; Altayb, Hisham N.; Elegail, Asrar M. A.; Ibrahim, Nuha Y.; Elamin, Bahaeldin K.

    2017-01-01

    Background. Currently, mutations in rpoB, KatG, and rrs genes and inhA promoter were considered to be involved in conferring resistance to rifampicin, isoniazid, and streptomycin in Mycobacterium tuberculosis (MTB). Objective. The aims of this study were to detect the prevalence of first-line tuberculosis (TB) drug resistance among a group of previously treated and newly detected TB patients, to determine the association between prevalence of multidrug resistance (MDR) and demographic information (age and sex), to explain genes correlated with MDR Mycobacterium tuberculosis, and to characterize MTB via 16S ribosomal RNA (16S rRNA) analysis. Methods. A hundred MTB isolates from Sudanese pulmonary TB patients were included in the study. The proportional method of drug susceptibility test was carried out on Löwenstein-Jensen media. Multiplex PCR of rpoB and KatG genes and inhA promoter was conducted; then rrs genes were amplified by conventional PCR and were sequenced. The sequences of the PCR product were compared with known rrs gene sequences in the GenBank database by multiple sequence alignment tools. Result. The prevalence of MDR was 14.7% among old cases and 5.3% among newly diagnosed cases. Conclusion. Mutations in rrs could be considered as a diagnostic marker. PMID:28197340

  9. Serotypes, antimicrobial resistance and genotypes of Streptococcus pneumoniae associated with infections in cancer patients in Brazil.

    Science.gov (United States)

    Cardoso, Nayara Torres; Santos, Bárbara Araújo; Barbosa, André Victor; Superti, Silvana Vargas; Teixeira, Lúcia Martins; Neves, Felipe Piedade Gonçalves

    2017-03-01

    We sought to characterize pneumococcal isolates associated with bacteremia, pneumonia and meningitis in cancer patients and to estimate the coverage of the available pneumococcal vaccines. Fifty isolates recovered from 49 patients attending a cancer reference center over a 1-year period were analyzed. The prevalent serotypes were: 23F (12%), 6A (8%), 3, 4, 20, and 23A (6% each). All isolates were susceptible to chloramphenicol, levofloxacin, rifampicin, and vancomycin. Resistance or reduced susceptibility to penicillin made up 14%, and one isolate was also intermediately resistant to ceftriaxone. The three (6%) erythromycin-resistant isolates presented the M or cMLSB phenotypes and harbored the mef(A/E) gene exclusively or along with the erm(B) gene. Twenty-two (44%) isolates were closely related to 11 international clones, being strongly associated with penicillin non-susceptibility. Combined immunization with the 13-valent conjugate and the 23-valent polysaccharide vaccines might contribute to reduce (76%) the burden of the pneumococcal infections in the population investigated.

  10. Phenotypic and Genotypic Analysis of Multidrug-Resistant Mycobacterium tuberculosis Isolates from Sudanese Patients

    Directory of Open Access Journals (Sweden)

    Solima M. A. Sabeel

    2017-01-01

    Full Text Available Background. Currently, mutations in rpoB, KatG, and rrs genes and inhA promoter were considered to be involved in conferring resistance to rifampicin, isoniazid, and streptomycin in Mycobacterium tuberculosis (MTB. Objective. The aims of this study were to detect the prevalence of first-line tuberculosis (TB drug resistance among a group of previously treated and newly detected TB patients, to determine the association between prevalence of multidrug resistance (MDR and demographic information (age and sex, to explain genes correlated with MDR Mycobacterium tuberculosis, and to characterize MTB via 16S ribosomal RNA (16S rRNA analysis. Methods. A hundred MTB isolates from Sudanese pulmonary TB patients were included in the study. The proportional method of drug susceptibility test was carried out on Löwenstein-Jensen media. Multiplex PCR of rpoB and KatG genes and inhA promoter was conducted; then rrs genes were amplified by conventional PCR and were sequenced. The sequences of the PCR product were compared with known rrs gene sequences in the GenBank database by multiple sequence alignment tools. Result. The prevalence of MDR was 14.7% among old cases and 5.3% among newly diagnosed cases. Conclusion. Mutations in rrs could be considered as a diagnostic marker.

  11. Duchenne's/Becker's muscular dystrophy: Analysis of genotype-feno-type correlation in 28 patients

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    Keckarević Milica

    2002-01-01

    Full Text Available Duchenne's and Becker's muscular dystrophy (DMD & BMD is a X linked disease caused by mutations in the dystrophic gene. DMD is the malign form of the disease, which significantly shortens the lifetime of the patient, while BMD has late onset with slow progression. Sixty five percent of DMD and BMD cases are caused by deletion of one or more exons in the dystrophic gene, while duplications cause these diseases in 6 to 7% of the cases. There are two hot spots for deletions and duplications. These are exons in the proximal part of the gene (3rd to 18th and exons of a distal part of the gene (45th to 52nd. The remaining 30% of DMD and BMD cases are caused by point mutations, small deletions or inversions in the dystrophic gene. The correlation between School of Medicine, University of Belgrade, Belgrade the severity of the disease and the position of deletion shows that most of the out of frame deletions cause DMD phenotype, while in frame deletions result in BMD pheno-type. We report on the results of 28 non-related DMD and BMD patients. In 57% of cases deletions were detected and all were found in the distal hot spot of the gene. These results suggest that in most of the cases, out of frame deletions produce DMD phenotype while in frame deletions result in BMD phenotype. This is in compliance with data from literature.

  12. Rapid virological response of telaprevir and boceprevir in a Brazilian cohort of HCV genotype 1 patients: a multicenter longitudinal study

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    Borba HHL

    2017-01-01

    Full Text Available Helena HL Borba,1 Astrid Wiens,1 Laiza M Steimbach,1 Fernanda S Tonin,1 Maria LA Pedroso,2 Cláudia AP Ivantes,3 Fernando Fernandez-Llimos,4 Roberto Pontarolo1 1Pharmaceutical Sciences Postgraduate Research Program, Department of Pharmacy, 2Gastroenterology Service, Hospital de Clínicas, Federal University of Paraná, 3Guidance and Counseling Center, Curitiba City Hall, Curitiba, Paraná, Brazil; 4Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines, University of Lisboa, Lisbon, Portugal Background: Chronic hepatitis C is a major public health issue, but there is a gap in the literature regarding the effectiveness and safety of direct-acting antiviral agents in the Brazilian population. The main aim of this study was to describe the effectiveness of boceprevir and telaprevir in patients treated at public health care institutions in Brazil.Materials and methods: A prospective longitudinal and multicenter study was conducted in five centers in the State of Paraná between September 2014 and June 2016. Data regarding effectiveness and safety were collected from medical records of patients treated with boceprevir or telaprevir. The effectiveness outcome comprised the rapid virological response (RVR. Multivariate analysis was performed to verify the influence of independent variables (ie, age, gender, baseline viral load on RVR achievement.Results: Data were collected from 117 patients with chronic hepatitis C virus (HCV genotype 1 infection. Fifteen patients received treatment with boceprevir and 102 received telaprevir. The mean age was 51.6 years, 64.1% were male, 44.4% were infected with HCV subtype 1a, 62.4% had a high baseline viral load (≥800,000 IU/mL and 33% were cirrhotic. Furthermore, 79.5% of patients achieved RVR (26.7% in the boceprevir group and 87.3% in the telaprevir group. Multivariate analysis demonstrated that the type of protease inhibitor (boceprevir or telaprevir and the baseline viral load

  13. Genotype-Phenotype Relationship in Patients with Mutations in Thyroid Hormone Transporter MCT8

    Science.gov (United States)

    Jansen, Jurgen; Friesema, Edith C. H.; Kester, Monique H. A.; Schwartz, Charles E.; Visser, Theo J.

    2008-01-01

    Loss-of-function mutations in thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to severe X-linked psychomotor retardation and elevated serum T3 levels. Most patients, for example those with mutations V235M, S448X, insI189, or delF230, cannot stand, walk, or speak. Patients with mutations L434W, L568P, and S194F, however, walk independently and/or develop some dysarthric speech. To study the relationship between mutation and phenotype, we transfected JEG3 and COS1 cells with wild-type or mutant MCT8. Expression and function of the transporter were studied by analyzing T3 and T4 uptake, T3 metabolism (by cotransfected type 3 deiodinase), Western blotting, affinity labeling with N-bromoacetyl-T3, immunocytochemistry, and quantitative RT-PCR. Wild-type MCT8 increased T3 uptake and metabolism about 5-fold compared with empty vector controls. Mutants V235M, S448X, insI189, and delF230 did not significantly increase transport. However, S194F, L568P, and L434W showed about 20, 23, and 37% of wild-type activity. RT-PCR did not show significant differences in mRNA expression between wild-type and mutant MCT8. Immunocytochemistry detected the nonfunctional mutants V235M, insI189, and delF230 mostly in the cytoplasm, whereas mutants with residual function were expressed at the plasma membrane. Mutants S194F and L434W showed high protein expression but low affinity for N-bromoacetyl-T3; L568P was detected in low amounts but showed relatively high affinity. Mutations in MCT8 cause loss of function through reduced protein expression, impaired trafficking to the plasma membrane, or reduced substrate affinity. Mutants L434W, L568P, and S194F showed significant residual transport capacity, which may underlie the more advanced psychomotor development observed in patients with these mutations. PMID:18187543

  14. Portal hypertension and an atypical reactive arthritis like presentation in a patient infected with hepatitis C virus genotype 3

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    Moushumi Lodh

    2014-01-01

    Full Text Available Background: Reactive arthritis (ReA is defined as a peripheral arthritis lasting longer than 1 month, associated with urethritis, cervicitis, or diarrhea. The reported annual incidence of ReA is approximately 30-40 cases per 100,000 adults, occurring commonly in the age group of 16 and 35 years. It is known to be associated with gastrointestinal infections with Shigella, Salmonella, and Campylobacter species and other microorganisms, as well as with genitourinary infections (especially with Chlamydia trachomatis. Case Report: This article reports the case of a 53-year-old, post-right total hip replacement, Indian man, with ReA, who presented with fever, respiratory distress, and abdominal discomfort. He complained of itching, tingling sensation, pain on urination, and retention of urine. He had right hip joint pain for 3 weeks, inability to move right leg since 10 days, and melena since 1 week. Laboratory tests revealed anemia, high liver and kidney function tests, elevated erythrocyte sedimentation rate, C reactive protein, procalcitonin and occult blood in stool. He tested positive for hepatitis C virus genotype 3. Gastroduodenoscopy revealed multiple apthoid ulcers at D2 and large gastric varix. Ultrasonography of whole abdomen revealed cholelithiasis and splenomegaly. Skin lesions and arthritis led to the diagnosis of associated ReA. The patient was managed conservatively and discharged in a stable condition. Conclusions: Our case is unlike classical ReA because the patient is older, HLA B27 negative, and without florid urethritis. Admitted for fever and lower urinary tract symptoms, along with respiratory distress, the primary objective of the emergency doctors was to prevent the patient from progressing to organ failure. The diagnosis of underlying atypical/incomplete ReA could easily have been missed without adequate awareness, dermatological consultation, and a skin biopsy.

  15. M. tuberculosis genotypic diversity and drug susceptibility pattern in HIV- infected and non-HIV-infected patients in northern Tanzania

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    van Soolingen Dick

    2007-05-01

    Full Text Available Abstract Background Tuberculosis (TB is a major health problem and HIV is the major cause of the increase in TB. Sub-Saharan Africa is endemic for both TB and HIV infection. Determination of the prevalence of M. tuberculosis strains and their drug susceptibility is important for TB control. TB positive culture, BAL fluid or sputum samples from 130 patients were collected and genotyped. The spoligotypes were correlated with anti-tuberculous drug susceptibility in HIV-infected and non-HIV patients from Tanzania. Results One-third of patients were TB/HIV co-infected. Forty-seven spoligotypes were identified. Fourteen isolates (10.8% had new and unique spoligotypes while 116 isolates (89.2% belonged to 33 known spoligotypes. The major spoligotypes contained nine clusters: CAS1-Kili 30.0%, LAM11- ZWE 14.6%, ND 9.2%, EAI 6.2%, Beijing 5.4%, T-undefined 4.6%, CAS1-Delhi 3.8%, T1 3.8% and LAM9 3.8%. Twelve (10.8% of the 111 phenotypically tested strains were resistant to anti-TB drugs. Eight (7.2% were monoresistant strains: 7 to isoniazid (INH and one to streptomycin. Four strains (3.5% were resistant to multiple drugs: one (0.9% was resistant to INH and streptomycin and the other three (2.7% were MDR strains: one was resistant to INH, rifampicin and ethambutol and two were resistant to all four anti-TB drugs. Mutation in the katG gene codon 315 and the rpoB hotspot region showed a low and high sensitivity, respectively, as predictor of phenotypic drug resistance. Conclusion CAS1-Kili and LAM11-ZWE were the most common families. Strains of the Beijing family and CAS1-Kili were not or least often associated with resistance, respectively. HIV status was not associated with spoligotypes, resistance or previous TB treatment.

  16. Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2: A project of the Kyushu University Liver Disease Study Group

    Institute of Scientific and Technical Information of China (English)

    Norihiro Furusyo; Akihide Masumoto; Shinji Shimoda; Kazuhiro Takahashi; Koichi Azuma; Jun Hayashi; Kyushu University Liver Disease Study Group; Masaki Katoh; Yuichi Tanabe; Eiji Kajiwara; Toshihiro Maruyama; Junya Shimono; Hironori Sakai; Makoto Nakamuta; Hideyuki Nomura

    2006-01-01

    AIM: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2,a multi-center study was retrospectively analyzed.METHODS: In total, 173 patients with HCV genotype 2stared to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk.RESULTS: The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9%vs 92.9 %), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8 % vs 92.0 %).CONCLUSION: The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16weeks.

  17. Association of H pylori cagA and vacA genotypes and IL-8 gene polymorphisms with clinical outcome of infection in Iranian patients with gastrointestinal diseases

    Institute of Scientific and Technical Information of China (English)

    Eskandar Kamali-Sarvestani; Abdulah Bazargani; Malihe Masoudian; Kamran Lankarani; Ali-Reza Taghavi; Mehdi Saberifiroozi

    2006-01-01

    AIM: To find out if a functional promoter polymorphism in the IL-8 gene along with cagA status and polymorphisms in vac4 gene influence the type of diseases in Iranian patients infected by H pylori.METHODS: IL-8 -251 A/T polymorphism was genotypedby oligonucleotide allele specific PCR (ASO-PCR) in a sample of 233 patients with H pylori infection undergoing upper gastrointestinal endoscopy. The presence of cagA gene and polymorphisms in vacA gene was also determined by PCR. Association of these genetic polymorphisms with the development of gastritis, peptic ulcers as well as gastric cancer was tested. RESULTS: When the patients with different clinical manifestations were compared according to the presence of cagA gene or various vacA genotypes, only the vacA genotypes were significantly different among gastritis, peptic ulcer and gastric cancer patients (x2= 17.8; P =0.001). Furthermore, there was a significant difference in the frequency of IL-8 -251 A/T genotypes between patients with gastric cancer and benign diseases (x2=10.47; P = 0.005).CONCLUSION: The IL-8 -251 A/T polymorphism and the polymorphisms in H pylori vacA gene are involved in limiting the infection outcome to gastritis and peptic ulcer or in favoring cancer onset in Iranian patients.

  18. Hepatitis A virus genotype IA-infected patient with marked elevation of aspartate aminotransferase levels.

    Science.gov (United States)

    Miura, Yoshifumi; Kanda, Tatsuo; Yasui, Shin; Takahashi, Koji; Haga, Yuki; Sasaki, Reina; Nakamura, Masato; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Nishizawa, Tsutomu; Okamoto, Hiroaki; Yokosuka, Osamu

    2017-02-01

    We describe a case of acute liver failure (ALF) without hepatic encephalopathy with marked elevation of aminotransferase due to hepatitis A, according to the revised Japanese criteria of ALF. This liver biopsy of the patient showed compatible to acute viral hepatitis and she immediately recovered without intensive care. She had no comorbid disorders. Of interest, phylogenetic tree analysis using almost complete genomes of hepatitis A virus (HAV) demonstrated that the HAV isolate from her belonged to the HAV subgenotype IA strain and was similar to the HAJFF-Kan12 strain (99% nucleotide identity) or FH1 strain (98% nucleotide identity), which is associated with severe or fulminant hepatitis A. Careful interpretation of the association between HAV genome variations and severity of hepatitis A is needed and the mechanism of the severe hepatitis should be explored.

  19. Analysis of HBV genotype, drug resistant mutations, and pre-core/basal core promoter mutations in Korean patients with acute hepatitis B.

    Science.gov (United States)

    Lee, Jong Ho; Hong, Sun Pyo; Jang, Eun Sun; Park, Sang Jong; Hwang, Seong Gyu; Kang, Sook-Kyoung; Jeong, Sook-Hyang

    2015-06-01

    Acute hepatitis B, caused by hepatitis B virus (HBV) strains with drug resistant mutations or pre-core/basal core promoter (PC/BCP) mutations, is a public health concern, because this infection is often associated with poor disease outcome or difficulty in therapeutic choice. The HBV genotype, the prevalence of drug resistant mutations, and PC/BCP mutations in Korean patients with acute hepatitis B were studied. From 2006 to 2008, 36 patients with acute hepatitis B were enrolled prospectively in four general hospitals. Among them, 20 showed detectable HBV DNA (median value was 4.8 log copies/mL). HBV genotyping and analysis of HBV mutations that conferred resistance against lamivudine, adefovir, or entecavir and of PC/BCP mutations were performed using highly sensitive restriction fragment mass polymorphism (RFMP) analysis. All 20 patients were infected with HBV genotype C, which causes almost all cases of chronic hepatitis B in Korea. No patient showed mutations that conferred resistance against lamivudine (L180M, M204V/I), adefovir (A181T, N236S), or entecavir (I169M, A184T/V, S202I/G, M250V/I/L). However, four patients had BCP mutations, and two had PC mutations. Platelet counts were significantly lower in the four patients with PC/BCP mutations compared to those with wild type. In this study, all acute hepatitis B patients had genotype C HBV strains with no drug resistant mutations. However, 20% showed PC/BCP mutations. This highlights the need for further study on the significance of PC/BCP mutations.

  20. The influence of 5-HTTLPR genotype on the association between the plasma concentration and therapeutic effect of paroxetine in patients with major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Tetsu Tomita

    Full Text Available INTRODUCTION: The efficacy of treatment with selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD can differ depending on the patient's serotonin transporter-linked polymorphic region (5-HTTLPR genotype, and the effects of varying plasma concentrations of drugs can also vary. We investigated the association between the paroxetine plasma concentration and clinical response in patients with different 5-HTTLPR genotypes. METHODS: Fifty-one patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale (MADRS was used to evaluate patients at 0, 1, 2, 4, and 6 weeks. The patients' paroxetine plasma concentrations at week 6 were measured using high-performance liquid chromatography. Additionally, their 5-HTTLPR polymorphisms (alleles S and L were analyzed using a polymerase chain reaction with specific primers. We divided the participants into two groups based on their L haplotype: the SS group and the SL and LL group. We performed single and multiple regression analyses to investigate the associations between MADRS improvement and paroxetine plasma concentrations or other covariates for each group. RESULTS: There were no significant differences between the two groups with regard to demographic or clinical data. In the SS group, the paroxetine plasma concentration was significantly negatively correlated with improvement in MADRS at week 6. In the SL and LL group, the paroxetine plasma concentration was significantly positively correlated with improvement in MADRS at week 6 according to the results of the single regression analysis; however, it was not significantly correlated with improvement in MADRS at week 6 according to the results of the multiple regression analysis. CONCLUSION: Among patients with MDD who do not respond to paroxetine, a lower plasma concentration or a lower oral dose of paroxetine might be more effective in those with the SS genotype, and a higher plasma concentration might

  1. Clinical significance of interleukin-1 genotype in smoking patients as a predictor of peri-implantitis: A case-control study

    Science.gov (United States)

    García-Delaney, Cristina; Sánchez-Garcés, Maria-Ángeles; Sánchez-Torres, Alba; Gay-Escoda, Cosme

    2015-01-01

    Background Interleukin-1 (IL-1) is a proinflammatory cytokine that plays an important role in the pathogenesis of periodontitis, and so it might be useful to detect high-risk cases of peri-implantitis. It has been reported that IL-1 polymorphisms and smoking habit have a synergic effect, increasing the incidence of peri-implantitis. The aim of the present study was to evaluate the relationship between IL-1 gene polymorphisms and peri-implantitis in smoking patients. Material and Methods A case-control study was performed in 27 patients with peri-implantitis and 27 patients with healthy implants. All patients included were smokers. IL-1A-C889T, IL-1B+C3953T and IL-1RN+T2018C were identified by polymerase chain reaction (PCR) amplification in order to establish a relation between these variables and the presence of peri-implantitis. A bivariate analysis was performed and odds-ratio (OR) were calculated. Results The incidence of peri-implantitis was significantly higher in patients with previous history of periodontitis (p=0.024; OR=10.9). Both groups were similar regarding IL-1A-C889T, IL-1B+C3953T and IL-1RN+T2018C genotypes. No increased risk in heavy smokers with IL-1 polymorphism was found. Conclusions IL-1 genotypes do not seem to be good predictors of peri-implantitis in the great majority of smoking patients. Furthermore, no synergic effect was found between IL-1 genotypes and heavy smokers. Patients with a previous history of periodontitis were more prone to peri-implantitis. Key words:Peri-implantitis, interleukin-1 genotype positive, case-control study, smoking. PMID:26449434

  2. Stenotrophomonas maltophilia Phenotypic and Genotypic Diversity during a 10-year Colonization in the Lungs of a Cystic Fibrosis Patient.

    Science.gov (United States)

    Pompilio, Arianna; Crocetta, Valentina; Ghosh, Dipankar; Chakrabarti, Malabika; Gherardi, Giovanni; Vitali, Luca Agostino; Fiscarelli, Ersilia; Di Bonaventura, Giovanni

    2016-01-01

    The present study was carried out to understand the adaptive strategies developed by Stenotrophomonas maltophilia for chronic colonization of the cystic fibrosis (CF) lung. For this purpose, 13 temporally isolated strains from a single CF patient chronically infected over a 10-year period were systematically characterized for growth rate, biofilm formation, motility, mutation frequencies, antibiotic resistance, and pathogenicity. Pulsed-field gel electrophoresis (PFGE) showed over time the presence of two distinct groups, each consisting of two different pulsotypes. The pattern of evolution followed by S. maltophilia was dependent on pulsotype considered, with strains belonging to pulsotype 1.1 resulting to be the most adapted, being significantly changed in all traits considered. Generally, S. maltophilia adaptation to CF lung leads to increased growth rate and antibiotic resistance, whereas both in vivo and in vitro pathogenicity as well as biofilm formation were decreased. Overall, our results show for the first time that S. maltophilia can successfully adapt to a highly stressful environment such as CF lung by paying a "biological cost," as suggested by the presence of relevant genotypic and phenotypic heterogeneity within bacterial population. S. maltophilia populations are, therefore, significantly complex and dynamic being able to fluctuate rapidly under changing selective pressures.

  3. Stenotrophomonas maltophilia phenotypic and genotypic diversity during a 10-year colonization in the lungs of a cystic fibrosis patient

    Directory of Open Access Journals (Sweden)

    Arianna Pompilio

    2016-09-01

    Full Text Available The present study was carried out to understand the adaptive strategies developed by S. maltophilia for chronic colonization of the cystic fibrosis (CF lung. For this purpose, 12 temporally isolated strains from a single CF patient chronically infected over a 10-year period were systematically characterized for growth rate, biofilm formation, motility, mutation frequencies, antibiotic resistance, and pathogenicity. Pulsed-field gel electrophoresis showed over time the presence of 2 distinct groups, each consisting of 2 different pulsotypes. The pattern of evolution followed by S. maltophilia was dependent on pulsotype considered, with strains belonging to pulsotype 1.1 resulting to be the most adapted, being significantly changed in all traits considered. Generally, S. maltophilia adaptation to CF lung leads to increased growth rate and antibiotic resistance, whereas both in vivo and in vitro pathogenicity as well as biofilm formation were decreased. Our results show for the first time that S. maltophilia can successfully adapt to a highly stressful environment such as CF lung by paying a biological cost, as suggested by the presence of relevant genotypic and phenotypic heterogeneity within bacterial population. This indicates that S. maltophilia populations are significantly more complex and dynamic than can be described by the analysis of any single isolate and can fluctuate rapidly to changing selective pressures.

  4. Identification of novel mutations by targeted exome sequencing and the genotype-phenotype assessment of patients with achromatopsia.

    Science.gov (United States)

    Li, Fen-Fen; Huang, Xiu-Feng; Chen, Jie; Yu, Xu-Dong; Zheng, Mei-Qin; Lu, Fan; Jin, Zi-Bing; Gan, De-Kang

    2015-10-22

    Achromatopsia (ACHM) is a severe congenital autosomal recessive retinal disorder caused by loss of cone photoreceptors. Here, we aimed to determine the underlying genetic lesions and phenotypic correlations in two Chinese families with ACHM. Medical history and clinical evaluation were obtained from both families. Targeted exome sequencing (TES) was performed on 201 disease-causing genes of inherited retinal dystrophies to screen for ACHM causative mutations in the two probands. The compound heterozygous mutations in CNGA3 (c.1074G > A, p.W358X; c.1706G > A, p.R569H) were identified in the first proband, and a novel homozygous mutation (c.968C > A, p.A323D) was detected in the other pedigree. The proposed topological model of the CNGA3 polypeptide suggested that the missense mutations primarily affected the transmembrane helix 5 and the cGMP-binding domain, respectively. Crystal structure modeling of the cyclic nucleotide-gated cation channel α-3 (CNGA3) protein encoded by the CNGA3 gene revealed an abnormal combined structure generated by R569H. We firstly used the TES approach to identify genetic alterations in patients with ACHM. We uncovered three mutations in CNGA3, including one novel mutation. Our results not only expand the genotypic spectrum for CNGA3 mutations, but also demonstrate that the TES approach is a valuable tool for molecular diagnosis.

  5. Stenotrophomonas maltophilia Phenotypic and Genotypic Diversity during a 10-year Colonization in the Lungs of a Cystic Fibrosis Patient

    Science.gov (United States)

    Pompilio, Arianna; Crocetta, Valentina; Ghosh, Dipankar; Chakrabarti, Malabika; Gherardi, Giovanni; Vitali, Luca Agostino; Fiscarelli, Ersilia; Di Bonaventura, Giovanni

    2016-01-01

    The present study was carried out to understand the adaptive strategies developed by Stenotrophomonas maltophilia for chronic colonization of the cystic fibrosis (CF) lung. For this purpose, 13 temporally isolated strains from a single CF patient chronically infected over a 10-year period were systematically characterized for growth rate, biofilm formation, motility, mutation frequencies, antibiotic resistance, and pathogenicity. Pulsed-field gel electrophoresis (PFGE) showed over time the presence of two distinct groups, each consisting of two different pulsotypes. The pattern of evolution followed by S. maltophilia was dependent on pulsotype considered, with strains belonging to pulsotype 1.1 resulting to be the most adapted, being significantly changed in all traits considered. Generally, S. maltophilia adaptation to CF lung leads to increased growth rate and antibiotic resistance, whereas both in vivo and in vitro pathogenicity as well as biofilm formation were decreased. Overall, our results show for the first time that S. maltophilia can successfully adapt to a highly stressful environment such as CF lung by paying a “biological cost,” as suggested by the presence of relevant genotypic and phenotypic heterogeneity within bacterial population. S. maltophilia populations are, therefore, significantly complex and dynamic being able to fluctuate rapidly under changing selective pressures. PMID:27746770

  6. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

    Science.gov (United States)

    Rodriguez-Auad, Juan Pablo; Rojas-Montes, Othon; Maldonado-Rodriguez, Angelica; Alvarez-Muñoz, Ma. Teresa; Muñoz, Onofre; Torres-Ibarra, Rocio; Vazquez-Rosales, Guillermo

    2015-01-01

    Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings. PMID:26779533

  7. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

    Directory of Open Access Journals (Sweden)

    Juan Pablo Rodriguez-Auad

    2015-01-01

    Full Text Available Monitoring antiretroviral therapy using measurements of viral load (VL and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6% of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

  8. Possible role of fructosamine 3-kinase genotyping for the management of diabetic patients.

    Science.gov (United States)

    Avemaria, Francesca; Carrera, Paola; Lapolla, Annunziata; Sartore, Giovanni; Chilelli, Nino Cristiano; Paleari, Renata; Ambrosi, Alessandro; Ferrari, Maurizio; Mosca, Andrea

    2015-08-01

    Diabetes mellitus is a global pandemic and continues to increase in numbers and significance. Several pathogenic processes are involved in the development of such disease and these mechanisms could be influenced by genetic, epigenetic and environmental factors. Non-enzymatic glycation reactions of proteins have been strongly related to pathogenesis of chronic diabetic complications. The identification of fructosamine 3-kinase (FN3K), an enzyme involved in protein deglycation, a new form of protein repair, is of great interest. FN3K phosphorylates fructosamines on the third carbon of their sugar moiety, making them unstable and causing them to detach from proteins, suggesting a protective role of this enzyme. Moreover, the variability in FN3K activity has been associated with some polymorphisms in the FN3K gene. Here we argue about genetic studies and evidence of FN3K involvement in diabetes, together with results of our analysis of the FN3K gene on a Caucasian cohort of diabetic patients. Present knowledge suggests that FN3K could act in concert with other molecular mechanisms and may impact on gene expression and activity of other enzymes involved in deglycation process.

  9. Genotype-phenotype correlation in Japanese patients with familial Mediterranean fever: differences in genotype and clinical features between Japanese and Mediterranean populations

    OpenAIRE

    Kishida, Dai; Nakamura, Akinori; Yazaki, Masahide; Tsuchiya-Suzuki, Ayako; MATSUDA, Masayuki; Ikeda, Shu-ichi

    2014-01-01

    Introduction Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent self-limiting fever and serositis that mainly affects Mediterranean populations. Many patients with FMF have been reported in Japan due to increasing recognition of this condition and the availability of genetic analysis for the gene responsible, MEFV. The present study was performed to elucidate the clinical characteristics of Japanese FMF patients and to examine the precise ge...

  10. Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients

    DEFF Research Database (Denmark)

    Hellemann, Dorthe; Larsson, Lars Anders Sune; Madsen, Hans O;

    2007-01-01

    .0045) at completion. No difference in MBL2 frequency was observed between patients and controls at baseline, and between patients classified as having sepsis or not. However, patients with the MBL2 O/O genotype had an increased frequency of Gram-positive bacterial infection (P = 0.01). Heterozygosity for MBL2 alleles...... by a PCR-based assay. Homozygosity for MBL2 variant alleles (O/O) causing MBL structural defects was associated with the highest adjusted mortality rate followed by homozygosity for the normal MBL2 allele (A/A) encoding high MBL levels, whereas heterozygous A/O patients had the most favour