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1.
Rheumatol Int ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31363829

RESUMO

In patients with gout, the serum uric acid (SUA) is usually lower during acute gouty attacks than during intercritical periods. It has been suggested that systemic inflammatory response can cause this phenomenon. The objective is to determine whether therapy with TNF inhibitors (TNFis) affects SUA levels in patients with systemic autoimmune rheumatic diseases (SARDs) and whether SUA changes correlate with pro-inflammatory cytokines or with the oxidative stress marker allantoin. In this study, SUA, CRP, creatinine, MCP-1, IFN-α2, IFN-γ, Il-1ß, IL-6, IL-8, IL-10, IL-12, IL-17a, IL-18, IL-23, IL-33, TNF-α, and allantoin levels were measured prior to and after 3 months of TNFis treatment in patients with SARDs. The values obtained in the biochemical assays were then tested for associations with the patients' demographic and disease-related data. A total of 128 patients (rheumatoid arthritis, n = 44; ankylosing spondylitis, n = 45; psoriatic arthritis, n = 23; and adults with juvenile idiopathic arthritis, n = 16) participated in this study. Among the entire patient population, SUA levels significantly increased 3 months after starting treatment with TNFis (279.5 [84.0] vs. 299.0 [102.0] µmol/l, p < 0.0001), while the levels of CRP, IL-6, IL-8, and MCP-1 significantly decreased. Male sex was the most powerful baseline predictor of ΔSUA in univariate and multivariate models. None of the measured laboratory-based parameters had statistically significant effects on the magnitude of ΔSUA. 3 months of anti-TNF therapy increased the levels of SUA in patients with SARDs, but neither the measured pro-inflammatory cytokines nor the oxidation to allantoin appeared responsible for this effect.

2.
Early Hum Dev ; 137: 104832, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31422343

RESUMO

BACKGROUND: Maternal characteristics may be associated with human milk macronutrients but no definite conclusions have been made to date. AIM: This study aimed to determine the relationship of maternal-associated factors on the content of macronutrients in human milk for the first six weeks after preterm delivery. STUDY DESIGN: Prospective observational cohort study. SUBJECTS: Milk samples were collected from mothers after premature birth between 24 + 0-35 + 6 weeks. OUTCOME MEASURES: Macronutrients and energy content were analyzed by mid-infrared transmission spectroscopy. Demographic and anthropometric data from mothers were systematically recorded. RESULTS: A total 1.558 human milk samples from 192 mothers were analyzed. Colostrum: higher protein (p = 0.001) and lower carbohydrate content (p = 0.003) were present in primiparous compared to multiparous milk. Vaginal birth was associated with increased carbohydrate content (p = 0.021). Fat and energy content in colostrum was not related to any maternal characteristics. Mature human milk: similarly to colostrum, higher protein content (p = 0.001) and lower carbohydrates content (p = 0.022) were observed in primiparous compared to multiparous milk. The mode of delivery was found to be another factor possibly influencing protein and carbohydrate levels (p = 0.036, p = 0.003, respectively). Pre-pregnancy obesity was associated with increased fat (p = 0.030) and energy content (p = 0.020) in human milk. On the contrary, smoking had a negative relationship to fat and energy content (p = 0.026, p = 0.007, respectively). CONCLUSION: Human milk macronutrient concentration after preterm delivery is associated with pre-pregnancy obesity, parity, mode of delivery and smoking. The impact of maternal factors on human milk composition should be taken into account in a strategy of feeding in premature infants.

3.
J Pediatr Endocrinol Metab ; 32(5): 479-488, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31075085

RESUMO

Background Females with Turner syndrome (TS) are prone to develop autoimmune diseases (AIDs). The X chromosome contains several immune-related genes. Growth hormone (GH) and estrogens modulate the immune system. We aimed to clarify whether the loss of a specific X chromosome gene locus and the administration of GH and estradiol facilitate the development of AIDs in TS females. Methods Retrospective data on clinical course, AIDs, karyotype and treatment were analyzed from a cohort of 286 Czech females with TS (current age 2.8-43.3 years; median age 18.7 years). The karyotypes were sorted using two different classification systems: a mosaicism-focused and an isochromosome (isoXq)-focused approach. Karyotype subgroups with a significantly higher prevalence of AIDs were further evaluated. Data of common therapies were correlated with the prevalence of AIDs. Results The most frequent AIDs were autoimmune thyroid disease (AITD; 37.4%; n = 107) and celiac disease (CD; 8.7%; n = 25). All karyotype subgroups were prone to develop AIDs. Females with an isolated Xp deletion had a significantly higher prevalence of AITD and CD compared to all other individuals with TS (AITD: 66.0% vs. 31.5%, p < 0.0001; CD: 17.4% vs. 7.2%; p = 0.04, respectively). We observed no link between the mean age at initiation as well as the duration of GH and/or estrogen administration and the occurrence of AIDs. Conclusions Isolated Xp deletion contributes to the development of AIDs in TS patients. The haploinsufficiency of genes located in Xpter-p11.2 may explain this observation. Common therapies used in TS do not modify the risk of AIDs.

4.
Cells ; 8(4)2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003562

RESUMO

ATP-binding cassette subfamily G member 2 (ABCG2) is a physiologically important urate transporter. Accumulating evidence demonstrates that congenital dysfunction of ABCG2 is an important genetic risk factor in gout and hyperuricemia; recent studies suggest the clinical significance of both common and rare variants of ABCG2. However, the effects of rare variants of ABCG2 on the risk of such diseases are not fully understood. Here, using a cohort of 250 Czech individuals of European descent (68 primary hyperuricemia patients and 182 primary gout patients), we examined exonic non-synonymous variants of ABCG2. Based on the results of direct sequencing and database information, we experimentally characterized nine rare variants of ABCG2: R147W (rs372192400), T153M (rs753759474), F373C (rs752626614), T421A (rs199854112), T434M (rs769734146), S476P (not annotated), S572R (rs200894058), D620N (rs34783571), and a three-base deletion K360del (rs750972998). Functional analyses of these rare variants revealed a deficiency in the plasma membrane localization of R147W and S572R, lower levels of cellular proteins of T153M and F373C, and null urate uptake function of T434M and S476P. Accordingly, we newly identified six rare variants of ABCG2 that showed lower or null function. Our findings contribute to deepening the understanding of ABCG2-related gout/hyperuricemia risk and the biochemical characteristics of the ABCG2 protein.

5.
Arthritis Res Ther ; 21(1): 77, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894219

RESUMO

BACKGROUND: ABCG2 is a high-capacity urate transporter that plays a crucial role in renal urate overload and extra-renal urate underexcretion. Previous studies have suggested an association between hyperuricemia and gout susceptibility relative to dysfunctional ABCG2 variants, with rs2231142 (Q141K) being the most common. In this study, we analyzed the ABCG2 gene in a hyperuricemia and gout cohort focusing on patients with pediatric-onset, i.e., before 18 years of age. METHOD: The cohort was recruited from the Czech Republic (n = 234) and consisted of 58 primary hyperuricemia and 176 gout patients, with a focus on pediatric-onset patients (n = 31, 17 hyperuricemia/14 gouts); 115 normouricemic controls were used for comparison. We amplified, sequenced, and analyzed 15 ABCG2 exons. The chi-square goodness-of-fit test was used to compare minor allele frequencies (MAF), and the log-rank test was used to compare empirical distribution functions. RESULTS: In the pediatric-onset cohort, two common (p.V12M, p.Q141K) and three very rare (p.K360del, p.T421A, p.T434M) allelic ABCG2 variants were detected. The MAF of p.Q141K was 38.7% compared to adult-onset MAF 21.2% (OR = 2.4, P = 0.005), to the normouricemic controls cohort MAF 8.5% (OR = 6.8, P <  0.0001), and to the European population MAF 9.4% (OR = 5.7, P <  0.0001). The MAF was greatly elevated not only among pediatric-onset gout patients (42.9%) but also among patients with hyperuricemia (35.3%). Most (74%) of the pediatric-onset patients had affected family members (61% were first-degree relatives). CONCLUSION: Our results show that genetic factors affecting ABCG2 function should be routinely considered in a hyperuricemia/gout diagnosis, especially in pediatric-onset patients. Genotyping of ABCG2 is essential for risk estimation of gout/hyperuricemia in patients with very early-onset and/or a family history.

6.
J Inherit Metab Dis ; 42(1): 128-139, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30740731

RESUMO

PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. METHODS: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. RESULTS: NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. CONCLUSIONS: Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.

7.
Mult Scler Relat Disord ; 22: 59-67, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29579644

RESUMO

BACKGROUND: A wide variety of interventions exists in physical therapy (PT), but knowledge about their use across different geographical regions is limited. This study investigated the use of PT interventions in people with multiple sclerosis (MS) across Europe. It aimed to determine whether regions differ in applying interventions, and explore whether factors other than regions play a role in their use. METHODS: In an online cross-sectional survey, 212 respondents from 115 European workplaces providing PT services to people with MS representing 26 countries (four European regions) participated. Cluster analysis, Pearson Chi-squared test and a Poisson regression model were used to analyze the data. RESULTS: Thirteen of 45 listed PT interventions were used by more than 75% of centers, while nine interventions were used by less than 25%. For 12 interventions, regions differed markedly in their use. Cluster analysis of centers identified four clusters similar in their intervention use. Cluster assignment did not fully align with regions. While center region was important, center size, number and gender of physical therapists working in the center, and time since qualification also played a role. Cluster analysis exploring the use of the interventions provided the basis for a categorization of PT interventions in line with their primary focus: 1. Physical activity (fitness/endurance/resistance) training; 2. Neuroproprioceptive "facilitation/inhibition"; 3. Motor/skill acquisition (individualized therapy led); 4. Technology based interventions. CONCLUSIONS: To our knowledge this is the first study that has explored this topic in MS. The results broaden our understanding of the different PT interventions used in MS, as well as the context of their use.


Assuntos
Esclerose Múltipla/terapia , Modalidades de Fisioterapia , Análise por Conglomerados , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Masculino , Análise de Regressão
8.
Rheumatology (Oxford) ; 56(11): 1982-1992, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28968913

RESUMO

Objectives: Common dysfunctional variants of ATP binding cassette subfamily G member 2 (Junior blood group) (ABCG2), a high-capacity urate transporter gene, that result in decreased urate excretion are major causes of hyperuricemia and gout. In the present study, our objective was to determine the frequency and effect on gout of common and rare non-synonymous and other functional allelic variants in the ABCG2 gene. Methods: The main cohort recruited from the Czech Republic consisted of 145 gout patients; 115 normouricaemic controls were used for comparison. We amplified, directly sequenced and analysed 15 ABCG2 exons. The associations between genetic variants and clinical phenotype were analysed using the t-test, Fisher's exact test and a logistic and linear regression approach. Data from a New Zealand Polynesian sample set and the UK Biobank were included for the p.V12M analysis. Results: In the ABCG2 gene, 18 intronic (one dysfunctional splicing) and 11 exonic variants were detected: 9 were non-synonymous (2 common, 7 rare including 1 novel), namely p.V12M, p.Q141K, p.R147W, p.T153M, p.F373C, p.T434M, p.S476P, p.D620N and p.K360del. The p.Q141K (rs2231142) variant had a significantly higher minor allele frequency (0.23) in the gout patients compared with the European-origin population (0.09) and was significantly more common among gout patients than among normouricaemic controls (odds ratio = 3.26, P < 0.0001). Patients with non-synonymous allelic variants had an earlier onset of gout (42 vs 48 years, P = 0.0143) and a greater likelihood of a familial history of gout (41% vs 27%, odds ratio = 1.96, P = 0.053). In a meta-analysis p.V12M exerted a protective effect from gout (P < 0.0001). Conclusion: Genetic variants of ABCG2, common and rare, increased the risk of gout. Non-synonymous allelic variants of ABCG2 had a significant effect on earlier onset of gout and the presence of a familial gout history. ABCG2 should thus be considered a common and significant risk factor for gout.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Gota/genética , Hiperuricemia/genética , Proteínas de Neoplasias/genética , Adolescente , Adulto , Idoso , Alelos , República Tcheca , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Grupo com Ancestrais Oceânicos/genética , Reino Unido , Adulto Jovem
9.
J Inherit Metab Dis ; 40(1): 49-74, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27778219

RESUMO

Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 µmol/L. Nevertheless, we recommend keeping the concentration below 100 µmol/L because levels fluctuate and the complications associated with high levels are so serious.


Assuntos
Cistationina beta-Sintase/deficiência , Homocistinúria/dietoterapia , Homocistinúria/tratamento farmacológico , Betaína/metabolismo , Homocisteína/metabolismo , Humanos , Metionina/metabolismo , Piridoxina/uso terapêutico
10.
BMC Health Serv Res ; 16(1): 552, 2016 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-27716390

RESUMO

BACKGROUND: Understanding the organisational set-up of physiotherapy services across different countries is increasingly important as clinicians around the world use evidence to improve their practice. This also has to be taken into consideration when multi-centre international clinical trials are conducted. This survey aimed to systematically describe organisational aspects of physiotherapy services for people with multiple sclerosis (MS) across Europe. METHODS: Representatives from 72 rehabilitation facilities within 23 European countries completed an online web-based questionnaire survey between 2013 and 2014. Countries were categorised according to four European regions (defined by United Nations Statistics). Similarities and differences between regions were examined. RESULTS: Most participating centres specialized in rehabilitation (82 %) and neurology (60 %), with only 38 % specialising in MS. Of these, the Western based Specialist MS centres were predominately based on outpatient services (median MS inpatient ratio 0.14), whilst the Eastern based European services were mostly inpatient in nature (median MS inpatient ratio 0.5). In almost all participating countries, medical doctors - specialists in neurology (60 %) and in rehabilitation (64 %) - were responsible for referral to/prescription of physiotherapy. The most frequent reason for referral to/prescription of physiotherapy was the worsening of symptoms (78 % of centres). Physiotherapists were the most common members of the rehabilitation team; comprising 49 % of the team in Eastern countries compared to approximately 30 % in the rest of Europe. Teamwork was commonly adopted; 86 % of centres based in Western countries utilised the interdisciplinary model, whilst the multidisciplinary model was utilised in Eastern based countries (p = 0.046). CONCLUSION: This survey is the first to provide data about organisational aspects of physiotherapy for people with MS across Europe. Overall, care in key organisational aspects of service provision is broadly similar across regions, although some variations, for example the models of teamwork utilised, are apparent. Organisational framework specifics should be considered anytime a multi-centre study is conducted and results from such studies are applied.


Assuntos
Esclerose Múltipla/terapia , Modalidades de Fisioterapia/organização & administração , Assistência Ambulatorial/estatística & dados numéricos , Europa (Continente) , Humanos , Pacientes Internados , Equipe de Assistência ao Paciente/organização & administração , Prescrições , Encaminhamento e Consulta/estatística & dados numéricos , Inquéritos e Questionários
11.
PLoS One ; 9(9): e107902, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25268603

RESUMO

OBJECTIVE: Using European descent Czech populations, we performed a study of SLC2A9 and SLC22A12 genes previously identified as being associated with serum uric acid concentrations and gout. This is the first study of the impact of non-synonymous allelic variants on the function of GLUT9 except for patients suffering from renal hypouricemia type 2. METHODS: The cohort consisted of 250 individuals (150 controls, 54 nonspecific hyperuricemics and 46 primary gout and/or hyperuricemia subjects). We analyzed 13 exons of SLC2A9 (GLUT9 variant 1 and GLUT9 variant 2) and 10 exons of SLC22A12 by PCR amplification and sequenced directly. Allelic variants were prepared and their urate uptake and subcellular localization were studied by Xenopus oocytes expression system. The functional studies were analyzed using the non-parametric Wilcoxon and Kruskall-Wallis tests; the association study used the Fisher exact test and linear regression approach. RESULTS: We identified a total of 52 sequence variants (12 unpublished). Eight non-synonymous allelic variants were found only in SLC2A9: rs6820230, rs2276961, rs144196049, rs112404957, rs73225891, rs16890979, rs3733591 and rs2280205. None of these variants showed any significant difference in the expression of GLUT9 and in urate transport. In the association study, eight variants showed a possible association with hyperuricemia. However, seven of these were in introns and the one exon located variant, rs7932775, did not show a statistically significant association with serum uric acid concentration. CONCLUSION: Our results did not confirm any effect of SLC22A12 and SLC2A9 variants on serum uric acid concentration. Our complex approach using association analysis together with functional and immunohistochemical characterization of non-synonymous allelic variants did not show any influence on expression, subcellular localization and urate uptake of GLUT9.


Assuntos
Proteínas Facilitadoras de Transporte de Glucose/genética , Gota/genética , Hiperuricemia/genética , Transportadores de Ânions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Animais , Transporte Biológico , Estudos de Casos e Controles , República Tcheca , Grupo com Ancestrais do Continente Europeu , Feminino , Expressão Gênica , Frequência do Gene , Gota/patologia , Humanos , Hiperuricemia/patologia , Masculino , Pessoa de Meia-Idade
12.
PLoS One ; 9(5): e97646, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24827988

RESUMO

OBJECTIVE: Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals. METHODS: The cohort consisted of 589 healthy subjects aged 18-65 years. We studied the associations between the serum uric acid concentration and the following: (i) demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii) the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii) selected genetic variants of the MTHFR (c.665C>T, c.1286A>C), SLC2A9 (c.844G>A, c.881G>A) and ABCG2 genes (c.421C>A). A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables. RESULTS: The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations. CONCLUSION: Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.


Assuntos
Transportadores de Cassetes de Ligação de ATP/sangue , Consumo de Bebidas Alcoólicas/sangue , Síndrome Metabólica/sangue , Proteínas de Neoplasias/sangue , Polimorfismo de Nucleotídeo Único , Ácido Úrico/sangue , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Idoso , Consumo de Bebidas Alcoólicas/genética , Consumo de Bebidas Alcoólicas/patologia , Estudos de Coortes , Feminino , Expressão Gênica , Proteínas Facilitadoras de Transporte de Glucose/sangue , Proteínas Facilitadoras de Transporte de Glucose/genética , Humanos , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Modelos Genéticos , Proteínas de Neoplasias/genética , Análise de Regressão , Fatores Sexuais
13.
J Nutr ; 142(8): 1403-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22695967

RESUMO

The role of folates as coenzymes in 1-carbon metabolism and the clinical consequences of disturbed folate metabolism are widely known. Folate status is a complex trait determined by both exogenous and endogenous factors. This study analyzed the association between 12 genetic variants and folate status in a Czech population with no folate fortification program. These 12 genetic variants were selected from 56 variant alleles found by resequencing the coding sequences and adjacent intronic regions of 6 candidate genes involved in folate metabolism or transport (FOLR1, FOLR2, FOLR3, MTHFR, PCFT, and RFC) from 29 individuals with low plasma and erythrocyte folate concentrations. Regression analyses of a cohort of 511 Czech controls not taking folate supplements revealed that only 2 variants in the MTHFR gene were associated with altered folate concentrations in plasma and/or erythrocytes. In our previous study, we observed that the common variant MTHFR c.665C > T (known as c.677C > T; p.A222V) was associated with decreased plasma folate concentrations. In the present study, we show in addition that the rare variant MTHFR c.1958C > T (p.T653M) is associated with significantly increased erythrocyte folate concentrations (P = 0.02). Multivariate regression analysis revealed that this uncommon variant, which is present in 2% of Czech control chromosomes, explains 0.9% of the total variability of erythrocyte folate concentrations; the magnitude of this effect size was comparable with that of the common MTHFR c.665C > T variant. This result indicates that the rare genetic variants may determine folate status to a similar extent as the common allelic variant.


Assuntos
Alelos , Ácido Fólico/metabolismo , Regulação da Expressão Gênica/fisiologia , Variação Genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adulto , Estudos de Coortes , República Tcheca , Suplementos Nutricionais , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Modelos Biológicos , Análise Multivariada , Mutação de Sentido Incorreto , Análise de Regressão
14.
Int Urogynecol J ; 22(5): 529-33, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20976440

RESUMO

INTRODUCTION AND HYPOTHESIS: Polypropylene meshes are frequently used in abdominal and vaginal reconstructive surgery. Recently, several authors have claimed that mesh-associated complications may be linked to mesh shrinkage. We have performed a prospective study with postoperative follow-up by ultrasound examination at two time points after Prolift anterior implantation to assess changes in the ultrasound appearance of mesh implants over time. METHODS: We assessed 36 patients who had undergone mesh implantation with Prolift anterior mesh for the correction of symptomatic anterior vaginal wall prolapse. During the surgery, we measured the actual midline length of the mesh (initial length). On the fourth postoperative day, we performed a vaginal ultrasound examination (US) to measure mesh length in the midsagittal plane. A second US was performed 3-5 months after surgery to repeat this measurement. RESULTS: There was a significant difference in mesh length determined before and 4 days after surgery (90.3 vs. 57.1 mm, P = <0.0001) indicating intraoperative folding. On comparing early and late postoperative ultrasound measurements, there was a reduction in length from 57.1 to 48.3 mm (P < 0.0001), indicating possible shrinkage or retraction. CONCLUSIONS: Intraoperative folding seems to be responsible for a large part of the difference between preoperative (in vitro) and postoperative (US) measurements of mesh dimensions, suggesting that surgical techniques may require adjustment.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/instrumentação , Prolapso de Órgão Pélvico/diagnóstico por imagem , Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas/efeitos adversos , Falha de Equipamento , Feminino , Seguimentos , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Ultrassonografia , Vagina/diagnóstico por imagem , Vagina/cirurgia
15.
Artigo em Inglês | MEDLINE | ID: mdl-19219379

RESUMO

INTRODUCTION AND HYPOTHESIS: The hypotheses of this study were that the TVT-SECUR procedure restricts urethral mobility, which leads to a greater likelihood of curative effect, and that the restriction might change over time. METHODS: Analyses of the position of the urethra and the tape of 85 patients who underwent the TVT-S procedure were performed using perineal ultrasonography. The efficacy of the TVT-S procedure was evaluated by cough test and by the questionnaire ICIQ-UI SF. RESULTS: Objectively, 53/85 (62%) of patients had a negative cough test, and in 32/85 (38%) of patients leakage of urine persisted. The TVT-S procedure restricts urethral mobility, and a higher degree of obstruction is associated with a higher likelihood of cure. The restriction weakens within the first 3 months after surgery. CONCLUSIONS: The objective cure rate of TVT-S procedure is low irrespective of placement technique. This may be due to insufficient restriction of urethral mobility.


Assuntos
Implantação de Prótese/métodos , Slings Suburetrais , Uretra/diagnóstico por imagem , Incontinência Urinária por Estresse/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Inquéritos e Questionários , Resultado do Tratamento , Ultrassonografia , Uretra/cirurgia
16.
Eur J Obstet Gynecol Reprod Biol ; 143(2): 121-5, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19181436

RESUMO

OBJECTIVE: The aim of this study is to present our first experience with a novel modification of the tension-free sling idea and to evaluate the safety and efficacy of this new procedure for the treatment of stress urinary incontinence in women. STUDY DESIGN: Eighty-five women with previously untreated stress urinary incontinence were recruited to participate in a clinical study. The efficacy of this surgical procedure was evaluated perioperatively and 3 months (+/-1 week) after operation--objectively by cough test and subjectively by the questionnaires Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire and the International Consultation on Incontinence Questionnaire-Short Form. All data were processed and statistical analyses performed in statistical environment R, version 2.5.1. RESULTS: From our results we conclude that there were no perioperative complications, objectively 62% of these patients were completely dry and 25% of patients improved. We observed a higher proportion of vaginal wall erosion (7/85) and urgency de novo (5/85) in the learning period group with respect to the routine period group. CONCLUSIONS: Our first experience with the tension-free vaginal tape secur system procedure is that it has a low percentage of perioperative complications. The learning curve has to be taken in account with reference to postoperative complications.


Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse/cirurgia , Idoso , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Slings Suburetrais/efeitos adversos , Resultado do Tratamento
17.
J Mol Med (Berl) ; 83(8): 647-54, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15806320

RESUMO

We have identified 21 different alpha-galactosidase A gene (GLA) mutations in 22 unrelated Czech and Slovak families with Fabry disease. Eleven of these mutations were novel (point mutations D93N, A135V, D155H, G171R, Q280K, G360S, Q330X, splicing errors c.194ins14, c.801ins36 and deletions c.674_732del59, g.3405_6021del2617). Genotyping of family members for family-specific mutations revealed 55 heterozygotes that manifested clinical symptoms of different severity. To examine the contribution of X-inactivation skewing to disease manifestation in Fabry heterozygotes, we have adopted the Mainz severity scoring scheme and compared the score values with the X-inactivation status in 39 carriers in an age-dependent manner. The age-score trendline of Fabry females who had a predominantly inactivated X-chromosome bearing a wild-type GLA allele (10 of 38 females) was markedly steeper than in the rest of the cohort. One female carrier with an inactivated mutated allele had a low score value when compared to the other heterozygotes of the same age. These data suggest that X-inactivation is indeed a major factor determining the severity of clinical involvement in Fabry heterozygotes. There was a statistically significant difference between the severity score values of heterozygotes with random and non-random X-chromosome inactivation at the 5% level of significance. Further studies will show if the degree of the wildtype allele inactivation will be useful as a predictive marker of severity of phenotype in Fabry heterozygotes. Although the correlation between X-inactivation skewing and presentation of the disease in Fabry heterozygotes has previously been suggested in the literature, this report is among the first attempts to examine this relationship systematically.


Assuntos
Doença de Fabry/genética , Inativação Gênica , Doenças Genéticas Ligadas ao Cromossomo X , alfa-Galactosidase/genética , Adolescente , Adulto , Fatores Etários , Criança , República Tcheca/epidemiologia , Doença de Fabry/epidemiologia , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Índice de Gravidade de Doença , Eslováquia/epidemiologia
18.
Mol Genet Metab ; 79(3): 167-75, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12855221

RESUMO

It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD.


Assuntos
Doença da Artéria Coronariana/etiologia , Cistationina beta-Sintase/genética , Homocisteína/sangue , Análise de Variância , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Frequência do Gene , Variação Genética , Genótipo , Heterozigoto , Humanos , Modelos Logísticos , Metionina/administração & dosagem , Metionina/sangue , Mutação , Polimorfismo Genético , Fatores de Risco
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