Needs of family caregivers of stroke patients: a longitudinal study of caregivers' perspectives.

BACKGROUND: After a stroke, patients often suffer from varying degrees of disability that require acute inpatient treatment and extended care at home. Therefore, the caregivers assume multiple responsibilities that can result in stress, particularly when their own needs are inadequately addressed during the patient's recovery. OBJECTIVES: This study aimed to explore the changing needs of family caregivers of stroke patients and factors related to the needs in four stages, before the transfer from intensive care unit to neurological unit, before discharge, 2 weeks post-hospitalization, and 3 months post-hospitalization. METHODS: The design of this study was based on longitudinal research, and the participants were family caregivers of stroke patients. Sixty family caregivers were recruited in this study. Data were collected at four time points by questionnaire. RESULTS: We found that the total number of needs of family caregivers decreased as the illness duration increased and that needs differed significantly between the four time points (P<0.01). Although the needs were different in each stage, health information, professional support, and community networks were the leading need domains in all four stages. The major factors affecting the care needs of family caregivers were the National Institutes of Health Stroke Scale scores of patients on admission, length of hospital stay, and physical dependence of patients. CONCLUSION: Family caregivers expected to obtain assistance and related care information from professionals during the course of the disease. Assessing the needs of family caregivers is important for health care workers in understanding problems from the caregivers' perspectives. Relevant information and counseling should be provided to family caregivers to help them access support when needed.

Adaptive robust genetic association tests using case-parents triad families.

Using the conditional likelihood, a model-specific score test can be derived under a given genetic model to test genetic association for case-parents triad family data. When the underlying genetic model is correctly specified, the score test is most powerful. However, it can lose substantial power when the model is misspecified. Several robust tests have been proposed to deal with the problem, such as the maximum test statistic, the maximin efficiency robust test, and the constrained likelihood ratio test. These tests have been shown to be robust against model misspecification compared with those model-specific score tests, but they are either time-consuming in computation or not sufficiently high in power robustness under some situations. In this study, a data-driven procedure is proposed to construct two adaptive robust genetic association tests WMERT and WMAX . The WMERT is simple in calculation and has fairly high power robustness. The empirical power of WMAX is quite stable and close to those of the model-specific score tests. The two proposed tests should be beneficial to practical genetic association studies. A real dataset consisting of neural tube defect triad families is used for illustration of the methods. R-scripts are also provided for numerical calculation of the proposed methods in practical studies.

A family-based robust multivariate association test using maximum statistic.

For characterizing the genetic mechanisms of complex diseases familial data with multiple correlated quantitative traits are usually collected in genetic studies. To analyze such data, various multivariate tests have been proposed to investigate the association between the underlying disease genes and the multiple traits. Although these multivariate association tests may have better power performance than the univariate association tests, they suffer from loss of testing power when the genetic models of the putative genes are misspecified. To address the problem, in this paper we aim to develop a family-based robust multivariate association test. We will first establish the optimal multivariate score tests for the recessive, additive, and dominant genetic models. Based on these optimal tests, a maximum-type robust multivariate association test is then obtained. Simulations are conducted to compare the power of our method with that of other existing multivariate methods. The results show that the robust multivariate test does manifest the robustness in power over all plausible genetic models. A practical data set is applied to demonstrate the applicability of our approach. The results suggest that the robust multivariate test is more powerful than the robust univariate test when dealing with multiple quantitative traits.

Gene-wide tagging study of the effects of common genetic polymorphisms in the α subunits of the GABA(A) receptor on epilepsy treatment response.

AIM: We aimed to identify the effect of SNPs in the α-subunits of GABAA receptors on epilepsy treatment outcomes by using a gene-wide tagging method. MATERIALS & METHODS: There were 720 epileptic patients included in the present study. A total of 136 tagging SNPs in GABRA1, GABRA2, GABRA3, GABRA4, GABRA5 and GABRA6 were genotyped by Illumina(®)GoldenGate(®) Genotyping platform. Clinical information, such as prescribed antiepileptic drugs, height, weight, epilepsy syndrome classification, etiology, number of attacks, renal function and liver function were collected. The associations between SNPs and epilepsy treatment outcomes were analyzed using SAS(®) version 9.1.3. Both multivariate logistic regression and multifactor dimensionality reduction analyses were performed. RESULTS: The results of single gene effects did not remain significant after Bonferroni's corrections. Further multivariate logistic regression and multifactor dimensionality reduction analyses of interactions between these genes showed that under adjustment of clinical factors, the epilepsy treatment outcomes were significantly associated with the genotype combinations of GABRA1 rs6883877, GABRA2 rs511310 and GABRA3 rs4828696 (p < 0.0001; adjusted r(2) = 0.149). CONCLUSION: Our results indicated that genetic variants in the α subunits of GABA(A) receptors may interactively affect the treatment responses of antiepileptic drugs. Further replication using an independent sample collection would be essential to confirm our findings.

Likelihood-based concordance tests for analysis of ascertained twin pair multinomial data.

The classic twin model design has a wide application in human genetics. Under the assumption that nongenetic effects are shared to the same degree by monozygotic (MZ) and dizygotic (DZ) twin pairs, a test of the equality of casewise concordances between MZ and DZ twins provides a clue to the influence of genetic and environmental factors on a disease. The casewise concordance is the conditional probability that given that one member of a twin pair is affected, the other is also affected. When disease prevalence is low or cost-effectiveness is considered, collection of twin pairs by ascertainment for performing casewise concordance analysis is required. In this article, by defining an overall casewise concordance parameter, several likelihood-based tests, such as likelihood ratio test LR, score test Score, the usual Wald test Wald and an alternative Wald test WaldA are investigated for a test of the equality of concordances between ascertained MZ and DZ twin pairs under multinomial models. Simulation studies were conducted for data with small sample sizes. The results show that the type I error rates and power of LR and Score are stable only when the overall casewise concordances are not extremely small or large. The Wald has higher power performance in most cases but would slightly inflate type I error rates; the WaldA is the most robust and recommended approach.

Association of polymorphisms in EPHX1, UGT2B7, ABCB1, ABCC2, SCN1A and SCN2A genes with carbamazepine therapy optimization.

AIM: Carbamazepine (CBZ) is one of the most widely used antiepileptic drugs. The aim of the present study is to investigate the impacts of polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathways of CBZ on the large interindividual variability in dosages and concentrations. METHODS & RESULTS: Genetic polymorphisms in the candidate genes were detected in 234 epileptic patients under maintenance CBZ monotherapy by real-time PCR and PCR-RFLP. Results of statistical analysis demonstrated that carriers of the variant SCN1A IVS5-91G>A and EPHX1 c.337T>C allele tended to require higher CBZ dosages and lower ln(concentration-dose ratios) than noncarriers (p < 0.0001) and the homozygous carriers also seemed to require higher CBZ dosages and lower ln(concentration-dose ratios) (p < 0.0001). In addition, the multiple regression model of concentration-dose ratio of CBZ also revealed that genetic variants in SCN1A, EPHX1 and UGT2B7 genes interactively affect the concentration-dose ratio of CBZ (adjusted r(2) = 55%). CONCLUSION: The present study identified genetic factors associated with CBZ therapy optimization and provided useful information for individualized CBZ therapy in epileptic patients. Further studies in larger populations are needed to confirm our results.

Association of genetic variants in six candidate genes with valproic acid therapy optimization.

AIMS: Valproic acid (VPA) is one of the most widely used antiepileptic drugs. The aim of the study was to investigate whether polymorphisms in genes related to pharmacokinetic and pharmacodynamic pathways of VPA were associated with the large interindividual variability in dosages and concentrations. METHODS & RESULTS: Genetic polymorphisms in six candidate genes were detected in 162 epileptic patients under maintenance with VPA monotherapy and stable seizure control by real-time PCR and PCR-RFLP. Results of statistical analysis demonstrated that carriers of the variant UGT1A6 19T>G, 541A>G and 552A>C allele tended to require higher VPA dosages and lower ln(concentration-to-dose ratios [CDRs]) than noncarriers (p < 0.0001) and the homozygous carriers also seemed to require higher VPA dosages and lower lnCDRs (p < 0.0001). On the other hand, carriers of the variant GRIN2B -200T>G allele were more likely to require lower VPA dosages than noncarriers (p < 0.0001) and the homozygous carriers also tended to require lower dosages and higher lnCDRs (p < 0.0001). In addition, the regression model of CDR of VPA also revealed that genetic variants in UGT1A6, GRIN2B and UGT2B7 genes interactively affect CDRs of VPA (adjusted r² = 47%). CONCLUSION: Although there was a limited sample size, the study identified genetic factors associated with VPA therapy optimization that has not been revealed, and provided useful information for individualized VPA therapy in epileptic patients.

A prevascularized tissue engineering chamber supports growth and function of islets and progenitor cells in diabetic mice.

Recent studies have shown that type 1 diabetes can be reversed in a murine model by islet transplantation to a vascularized tissue engineering chamber. In preliminary experiments using a prevascularized chamber we observed that islet grafts not functioning initially can show a delayed onset of function several weeks after implantation. We sought to characterize this phenomenon. Islets were transplanted into prevascularized tissue engineering chambers based on the epigastric vessels in streptozotocin induced diabetic C57BL/6J mice. Animals were transplanted with 500 islets and observed at 1, 4, 8 and 16 weeks post transplantation. Weekly blood glucose (BG) measurements revealed an average onset of maintained graft function 6.8 weeks post transplantation. Graft function was proven by a return to a diabetic state following chamber removal. Mature grafts showed islet tissue clustered together within the tissue construct. The quantity of endocrine tissue staining positive for insulin correlated with graft function at 8 and 16 weeks. However, at 1 and 4 weeks, islet tissue was not evidently visible as observed by endocrine staining. All islet tissue showed dense vascularization and sporadic sympathetic innervation, irrespective of the graft's function. Immunopositive cells for Cytokeratin-7 and -19 were observed in the grafts at early time points and hormone producing cells appear to have been differentiated from these progenitors. Our data demonstrates that pancreatic duct-derived progenitors remain viable in vivo and eventually differentiate and mature to functional islets following transplantation. Our prevascularized tissue-engineering chamber in the groin supports maturation and function of the grafted tissue by two months after implantation.

Leisure-time physical activities for community older people with chronic diseases.

AIMS: (1) To explore the types and three components (frequency, duration and caloric expenditure) of leisure-time physical activity in community older people with chronic diseases. (2) To identify leisure-time physical activity-related factors in these community older people. BACKGROUND: Previous research has focused primarily on measuring the actual physiological or psychological benefits of exercise or leisure-time physical activity, little is known about the factors that determine the frequency, intensity and duration of exercise or leisure-time physical activity. The identification of reliable predictors of the various components of leisure-time physical activity will enable healthcare providers to intervene and change the patterns of leisure-time physical activity in the sedentary older people more effectively. DESIGN: A cross-sectional design was used for this study. METHODS: Participants were recruited from the Xinyi District in Taipei, Taiwan. A total of 206 older people were recruited and were asked to complete three questionnaires during a face-to-face interview with a researcher at the activity setting. RESULTS: The results showed that walking leisurely was the most frequent leisure-time physical activity for participants. The age, gender, living arrangement, affective feeling and environmental control were significant variables of leisure-time physical activity. CONCLUSIONS: The study constructs accounted for moderate amounts of variance (22% for leisure-time physical activity frequency, 27% for leisure-time physical activity duration and 24% for leisure-time physical activity caloric expenditure). This study also showed that different variables play different influential roles in the different components of LTPA. RELEVANCE TO CLINICAL PRACTICE: An effective intervention strategy for improving leisure-time physical activity of older people may involve tailoring the type, format, intensity, frequency and duration of a physical activity according to an individual's needs. This study described some environmental barriers to LTPA and recommended an increase in the accessibility to LTPA areas.

Correlation of Occupational Stress Index with 24-hour Urine Cortisol and Serum DHEA Sulfate among City Bus Drivers: A Cross-sectional Study.

OBJECTIVES: The questionnaire of occupational stress index (OSI) has been popular in the workplace, and it has been tailored for bus drivers in Taiwan. Nevertheless, its outcomes for participants are based on self-evaluations, thus validation by their physiological stress biomarker is warranted and this is the main goal of this study. METHODS: A cross-sectional study of sixty-three city bus drivers and fifty-four supporting staffs for comparison was conducted. Questionnaire surveys, 24-hour urine cortisol testing, and blood draws for dehydroepiandrosterone-sulfate (DHEA-S) testing were performed. The measured concentrations of these biological measures were logarithmically transformed before the statistical analysis where various scores of stressor factors, moderators, and stress effects of each OSI domain were analyzed by applying multiple linear regression models. RESULTS: For drivers, the elevated 24-hour urine cortisol level was associated with a worker's relationship with their supervisor and any life change events in the most recent 3 months. The DHEA-S level was higher in drivers of younger age as well as drivers with more concerns relating to their salary and bonuses. Non-drivers showed no association between any stressor or satisfaction and urine cortisol and blood DHEA-S levels. CONCLUSION: Measurements of biomarkers may offer additional stress evaluations with OSI questionnaires for bus drivers. Increased DHEA-S and cortisol levels may result from stressors like income security. Prevention efforts towards occupational stress and life events and health promotional efforts for aged driver were important anti-stress remedies.

An endoscopic training model to improve accuracy of colonic polyp size measurement.

PURPOSE: Most studies of colonic polyps rely on visual estimation when regarding polyp size; however, the reliability of a visual estimate is questionable. Our study aims to develop a training model to improve the accuracy of size estimation of colonic polyps in vivo. METHODS: Colon polyps were recorded on 160 video clips during colonoscopy. The size of each polyp was estimated by visual inspection and subsequently measured with a flexible linear measuring probe. The study included a pretest, an intervention, and a posttest. The pretest included 160 video clips, which comprised the visual-estimation portion of the study. The intervention was an educational model consisting of 30 video clips which included a visual-estimation section and a linear-measuring-probe section, designed to help the endoscopists to compare their visual estimate of size with the measured size of the polyps. The posttest included the 160 video clips used in the pretest, presented in random order. Intraobserver agreement and diagnostic accuracy were compared before and after the training session. RESULTS: Eight beginners and four experienced colonoscopists were enrolled. The overall kappa (kappa) values of intraobserver agreement for pretest and posttest were 0.74 and 0.85 for beginner group as well as 0.83 and 0.88 for experienced group, respectively. The overall diagnostic accuracy improved from 0.52 to 0.78 for beginner group and 0.71 to 0.87 for experienced group (P < 0.05) after education with the training model. CONCLUSIONS: This training model could help endoscopists improve the accuracy of measurement of polyps on colonoscopy in a short period. The durability of learning effect needs further investigation.

Different prevalence rates of Parkinson's disease in urban and rural areas: a population-based study in Taiwan.

BACKGROUND: Rural living has long been debated as a risk factor for idiopathic Parkinson's disease (IPD). But few community-based studies compared this difference between urban and rural areas. METHODS: Population-based surveys by neurologists using a standardized diagnostic protocol were conducted in the urban areas of Keelung City and compared the prevalence rates of IPD with those we had previously determined in the rural area of Ilan County, Taiwan. Subjects were diagnosed with IPD when at least 2 of the 4 cardinal signs of parkinsonism were present and by exclusion of secondary parkinsonism. Gender-specific age-standardized prevalence rates of IPD by using the 1970 and 2000 US censuses were calculated for comparison. RESULTS: The participation rate was 84.9%. The crude prevalence rate of IPD in persons aged 40 years and over was 706 (95% CI: 551-864) per 100,000 population. The age-adjusted prevalence rates by using the 1970 US census were 633 (95% CI: 620-646) for people aged 40 and over and 230 (95% CI: 227-234) for all ages. Our results were similar to those obtained in Sicily, Rotterdam, and 3 communities in China. Moreover, the prevalence rates of IPD in Keelung, the urban area studied, were twice as high as those in Ilan, the rural area studied (p < 0.001). CONCLUSIONS: Our results suggest that urban living is more important as a risk factor for IPD development than rural living in Taiwan.

Ethnic-specific prevalence of hepatitis B/C virus infection in Pin-Jen, Taiwan.

OBJECTIVES: The study aimed to estimate prevalence rate of hepatitis B/C virus infection by three ethnic groups including Hakka, Minnan, and Mainlander in Taiwan where there was a high incidence of hepatocellular carcinoma. METHODS: We enrolled a total of 5007 people aged 30 years or older who participated in Li-Shin Out-Reaching Neighboring Screening (LIONS) project in 2004-2005 in Pin-Jen township of Taoyuan county. The ethnic group was classified in the current study by using the criteria on the basis of the ethnicity of mother of participants. We collected the character of participants, hepatitis B/C virus infection, and life-style factors for the comparison across three ethnic groups. RESULTS: The highest positive rate of hepatitis B virus infection was seen in Minnan descendants (15.1%), followed by Hakka descendants (11.4%), and Mainlander descendants (6.6%). The difference by three groups was statistically significant (P<.001). Positive hepatitis B virus infection declined with age whereas positive hepatitis C virus infection increased with age regardless of ethnic group. By using ecological analysis, the higher proportion of Minnan was positively correlated to the elevated incidence of hepatocellular carcinoma (HCC) (correlation coefficient=.46, P=.03). CONCLUSIONS: Our population-based study shows prevalence rate of hepatitis B and C virus infection varies with ethnic group, with higher rate in Minnan. This finding was consistent with the ecological result, the higher the composition of Minnan the higher the incidence of HCC.

Unplanned readmission within the most recent postoperative year of heart transplant patients in Taiwan.

AIMS: The aim of this study was to examine the rate of unplanned readmissions within the most recent postoperative year for heart transplant patients and the causes and contributing factors leading to such readmissions. BACKGROUND: Advances in medical technology have significantly increased the survival rate of heart transplant patients. However, several postoperative complications make it common for patients to be readmitted to hospitals. An 'unplanned readmission' rate will better reflect the quality of postdischarge care than will mortality rate alone. Little research has been conducted on the heart transplant population in Taiwan. DESIGN: Descriptive, cross-sectional. METHODS: Data were collected from a purposive sample by structured questionnaires and medical record reviews. RESULTS: Seventy-one patients were recruited at different times after heart transplantation. The unplanned readmission rate was 35.2% in the most recent postoperative year. The unplanned readmission rate was 52.2% for patients who had received transplantation five years ago or less, which was significantly higher than that for patients who had received transplantation more than five years ago (27.1%). Leading causes of unplanned readmission included infection (31.8%), rejection (25.0%) and cardiac allograft vasculopathy (18.2%). Blood urea nitrogen and creatinine levels were significantly higher in readmitted patients than in patients who were not (t = 2.09, p < 0.05 and t = 2.12, p < 0.05, respectively). CONCLUSION: To reduce unplanned readmissions, the health professionals must continuously evaluate and monitor for adverse effects of treatment on patients, providing suitable guidance to equip the patient with the knowledge and ability to manage symptoms appropriately. RELEVANCE TO CLINICAL PRACTICE: Continuous postoperative follow-up should be performed for patients. Nurses can function as the patient's evaluator, advisor, educator and advocator, to conduct postoperative care and carry out follow-up plans to prevent readmission.

Association of polymorphisms in NR1I2 and ABCB1 genes with epilepsy treatment responses.

OBJECTIVES: The aim of this study was to investigate whether the polymorphisms in the NR1I2 and ABCB1 genes were associated with epilepsy treatment responses. METHODS & RESULTS: NR1I2and ABCB1 polymorphisms were genotyped in 114 drug-resistant epileptic patients, 213 seizure-free patients and 287 normal controls. Highly specific real-time PCR was applied to detect the variants by using TaqMan allelic specific probe. For a single gene test, it was demonstrated that 3435C>T in the ABCB1 gene had a significant effect on epilepsy treatment responses, but polymorphisms in the NR1I2 gene did not. Further analysis using a logistic regression model revealed that only 2677G>T and 3435C>T in the ABCB1 gene and their interaction term were associated with drug-resistant epilepsy after adjustment for etiology and epilepsy classification. In the present study, the polymorphisms in the NR1I2 gene were not significantly associated with epilepsy treatment responses. CONCLUSION: Our results indicated that 2677G>T and 3435C > T in the ABCB1 gene contributed to drug-resistant epilepsy. Although biologically plausible, the polymorphisms in NR1I2 investigated in the present study did not play a role in epilepsy treatment responses. Other unveiled genetic variants in the NR1I2 gene that may have the potential to affect ABCB1 gene expression are worth further investigation in future studies.

Twin concordances test for ascertained trichotomous traits data.

In human genetics, twin studies are widely underwent for investigation of the genetic influence on diseases. There are several measures that had been proposed to evaluate the similarity between two twins for dichotomous traits when the twins are sampled at random. These measures include the correlations, odds ratios, and casewise and pairwise concordances. When data are sampled through an ascertainment procedure, truncated data are formed. Under this circumstance, odds ratio cannot be defined and correlations cannot be correctly estimated. However, concordance measures for dichotomous traits can still be estimated using the likelihood method. On the other hand, though theoretically concordance measures can be extended to trichotomous traits, how to define them and to derive their estimators for ascertained trichotomous traits data have not been thoroughly discussed. In this study, we aim to address several relevant issues for ascertained trichotomous traits data. We define two new (casewise and pairwise) concordance measures for trichotomous traits and demonstrate how to apply a so-called 'self-contained subsets method (SCSM)' to estimation of twin concordances for ascertained data. We show that this method can obtain the same estimates as the likelihood method in an easier way and derive the asymptotic variances of the SCSM estimates under ascertainment. We establish the testing procedure for test of the equality of concordance measures between monozygotic twin pairs and dizygotic twin pairs, and illustrate the methods with a real data set and conduct Monte Carlo simulation to investigate its power performance.

A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose.

OBJECTIVES: A broad range of phenytoin doses is used in clinical practice, with the final 'maintenance' dose normally determined by trial and error. A common functional polymorphism in the SCN1A gene (one of the genes encoding the drug target) has been previously associated with maximum dose of phenytoin used clinically, and also maximum dose of carbamazepine, another antiepileptic drug with the same drug target. METHODS: We have related variation at the SCN1A IVS5-91 G>A polymorphism to maximum dose and to maintenance dose of phenytoin in 168 patients with epilepsy treated with phenytoin. We also related genotype to phenytoin serum levels at maximum dose and at maintenance dose of phenytoin. We genotyped the polymorphism using an Applied Biosystems Taqman assay. RESULTS: The polymorphism is associated with phenytoin serum concentration at maintenance dose (P=0.03). In a reduced cohort of 71 patients receiving phenytoin monotherapy this association is also significant (P=0.03). Neither association remains significant after Bonferroni correction for multiple testing. CONCLUSIONS: These results are not a replication of the original study. They do, however, support the hypothesis that this polymorphism influences the clinical use of phenytoin. They also demonstrate the utility of using multiple phenotypes in pharmacogenetics studies, particularly when attempting to separate pharmacokinetic and pharmacodynamic effects. As the SCN1A polymorphism affects phenytoin pharmacodynamics, it is particularly useful to obtain data on serum levels in addition to dose because association of a pharmacodynamic variant may be stronger with serum levels than dose as the serum level may eliminate or reduce pharmacokinetic variability.

Long-term results of anti-Helicobacter pylori therapy in early-stage gastric high-grade transformed MALT lymphoma.

BACKGROUND: Several independent clinical studies have reported that Helicobacter pylori eradication therapy could achieve complete remission in some patients with H. pylori-positive early-stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: To compare the long-term results of anti-H. pylori therapy in early-stage, gastric low-grade and high-grade transformed MALT lymphoma, two multicenter prospective studies of anti-H. pylori therapy for early-stage gastric lymphoma conducted in Taiwan, one for low-grade MALT lymphoma, with 34 patients enrolled from March 1996 through April 1999, and one for high-grade transformed tumors (diffuse large B-cell lymphoma with features of MALT, DLBCL[MALT] lymphoma), with 24 patients enrolled since June 1995, were directly compared. In both studies, patients generally received 2 weeks of antibiotics and had multiple sequential follow-up endoscopic examinations until complete histologic remission (CR) or disease progression; patients were monitored through January 31, 2004. CR was defined as regression of lymphoid infiltration to Wotherspoon's score of 2 or less on all pathologic sections of endoscopic biopsy specimens. All statistical tests were two-sided. RESULTS: The H. pylori-positive rate among the 34 low-grade patients was 94% (32 of 34). All 24 selected high-grade patients were H. pylori positive. H. pylori was eradicated in 97% (30 of 31) of evaluable H. pylori-positive low-grade patients and in 92% (22 of 24) of high-grade patients, which led to CR in 80% (24 of 30, 95% confidence interval [CI] = 65% to 95%) and 64% (14 of 22, 95% CI = 42% to 86%) of patients, respectively. None of the five patients who were either initially H. pylori negative or had persistent H. pylori infection after antibiotics achieved CR. After median follow-up of more than 5 years in complete responders, tumor recurrence was observed in three (13%) low-grade patients but not in high-grade patients. CONCLUSIONS: Anti-H. pylori therapy may be considered as one of the treatment options for early-stage H. pylori-positive gastric DLBCL(MALT), and large-scale prospective studies to validate its use as first-line therapy for such tumors should be undertaken.

Complex haplotypic effects of the ABCB1 gene on epilepsy treatment response.

OBJECTIVES: The aim of this study was to investigate the association of the complex haplotype system of the adenosine triphosphate-binding cassette B1 (ABCB1) gene with the epilepsy treatment response. METHODS AND RESULTS: Ten polymorphisms were genotyped in 108 drug-resistant epileptic patients, 223 seizure-free patients and 287 normal controls. Highly significant linkage disequilibrium was shown among exon 12 C1236T, exon 21 G2677T and exon 26 C3435T. Haplotypic analysis demonstrated that patients with the CGC, TGC, and TTT haplotypes were more likely to be drug resistant. Further analysis of haplotype combinations demonstrated that drug-resistant patients tended to have the CGC/CGC, CGC/TGC, CGC/TTT, and TGC/TTT haplotype combinations over the seizure-free patients and controls (all p-values < 0.0001). In contrast, patients with the TTC/TTC, TTC/CGT, TTC/TGT, CGT/CGT and TGT/CGT haplotype combinations were more likely to be seizure-free (all p-values<0.0001 except CGT/CGT [p=0.0063]). CONCLUSION: Our results showed that the three loci, C1236T, G2677T and C3435T, jointly influenced the treatment response for epileptic patients. They should be regarded together as a complex polymorphic drug-response system. These findings suggest that examination of the haplotypes of the three loci could be useful in predicting drug resistance in epilepsy.