CTLA-4 gene polymorphisms and their influence on predisposition to autoimmune thyroid diseases (Graves’ disease and Hashimoto's thyroiditis)

Introduction

Autoimmune thyroid disease (AITD) is associated with both genetic and environmental factors which lead to the overactivity of immune system. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene polymorphisms belong to the main genetic factors determining the susceptibility to AITD (Hashimoto''s thyroiditis, HT and Graves'' disease, GD) development. The aim of the study was to evaluate the relationship between CTLA-4 polymorphisms (A49G, 1822 C/T and CT60 A/G) and HT and/or GD in Polish patients.

Material and methods

Molecular analysis involved AITD group, consisting of HT (n=28) and GD (n=14) patients, and a control group of healthy persons (n=20). Genomic DNA was isolated from peripheral blood and CTLA-4 polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism method, using three restriction enzymes: Fnu4HI (A49G), BsmAI (1822 C/T) and BsaAI (CT60 A/G).

Results

Statistical analysis (χ² test) confirmed significant differences between the studied groups concerning CTLA-4 A49G genotypes. CTLA-4 A/G genotype was significantly more frequent in AITD group and OR analysis suggested that it might increase the susceptibility to HT. In GD patients, OR analysis revealed statistically significant relationship with the presence of G allele. In controls, CTLA-4 A/A genotype frequency was significantly increased suggesting a protective effect. There were no statistically significant differences regarding frequencies of other genotypes and polymorphic alleles of the CTLA-4 gene (1822 C/T and CT60 A/G) between the studied groups.

Conclusions

CTLA-4 A49G polymorphism seems to be an important genetic determinant of the risk of HT and GD in Polish patients.     

Practice patterns with hormone therapy after surgical menopause

Objectives

The aim of this study was to examine hormone therapy (HT) users’ experiences, perceptions and information sources in 2009.

Study design

Questionnaire survey was conducted in 2009 among women using HT. The questionnaire (n = 500) was distributed from pharmacies across Finland. The response rate was 58% (n = 281).

Main outcome measures

The survey measured self-reported benefits and adverse reactions, fears and information sources.

Results

The number of systemic HT users reporting fears was 50% (n = 99). The most common fear was breast cancer (27%). Systemic HT users who had considered discontinuation of HT or had temporarily discontinued HT experienced fears more often than other respondents (p < 0.001 and p = 0.029). The most common source of information on the benefits of HT in both surveys was a physician (91%), whereas the most common source of information on adverse reactions was the media (54%). Vaginal HT users had experienced similar fears as users of systemic HT.

Conclusions

Women using HT need more information about the risks of HT from their physician. This is especially important for women who are not able to manage the symptoms without HT, but have tried or considered discontinuation and for vaginal HT users.     

The 8-hydroxydeoxyguanosine concentrations according to hormone therapy and S326C polymorphism of OGG1 gene in postmenopausal women

Background

The 8-hydroxydeoxyguanosine (8-OHdG) is widely used for determination of DNA damage since it is excised from oxidative damaged DNA with endonuclease repair enzymes coded by 8-oxoguanine DNA N-glycosylase gene (OGG1). The present study aimed at investigating whether hormone therapy (HT) may influence on the blood/urinary 8-OHdG levels and whether the level of 8-OHdG is different according to OGG1 S326C polymorphism in postmenopausal women receiving HT.

Methods

In 102 postmenopausal women receiving HT, the 8-OHdG levels were measured in the blood and urine using high performance liquid chromatography (HPLC) before HT and 3 months after HT. The genotyping of the S326C polymorphism of the OGG1 was performed by polymerase chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) analysis.

Results

After HT, mean blood 8-OHdG level significantly decreased compared to those before HT (P = 0.003), while urinary 8-OHdG level did not show any difference according to HT. Pre-HT level of 8-OHdG was not different according to OGG1 genotypes and similar finding was demonstrated in post-HT 8-OHdG concentration.

Conclusions

These findings imply that hormone therapy can reduce blood 8-OHdG concentration, one of the markers of oxidative damage. Further study is needed to confirm this association in larger population.     

Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma

Background

Cancer stem cells (CSCs) are thought to be a critical subpopulation in tumor development, progression, metastasis and recurrence, and the identification of these cells is an initial step in understanding their role in oncogenesis and in seeking valuable markers for diagnosis or development of targeting therapeutics.

Aims

To identify CSCs in hepatocellular carcinoma (HCC) specimens and define their tissue specificity.

Methods

Immunohistochemical staining of CSC markers: CD44, CD90, CD133 and aldehyde dehydrogenase (ALDH) was performed in 25 HCC specimens, 4 hepatoblastomas, 8 peri-malignant tissues, and 19 cases of viral hepatitis.

Results

The positivity of CD44 staining in HCC specimens was significantly lower than in viral hepatitis specimens. The positive rate of CD133 in HCC was similar to viral hepatitis specimens. CD133⁺ cells were largely localized to ALDH-positive cells in HCC as revealed by confocal microscopy. In contrast, the co-expression of both markers was visualized within vessels or in the portal areas in viral hepatitis. Moreover, among 7 liver specimens adjacent to HCC tissue, 3-6 samples were positive for CD44, CD90, CD133 and ALDH, especially in dysplastic cells. One of 4 hepatoblastoma cases was positive for all these markers; whereas, the other three specimens were negative for all these CSC markers.

Conclusions

In HCC and dysplastic tissues, clusters of CD133⁺/ALDH^high cells were identified. The use of cancer stem cell markers to screen tissues with chronic liver diseases provides limited guidance in the identification of malignant cells.     

Wellness in community living adults: the Weigh to Life program

Objective

To examine physiological and health-related quality of life (HRQOL) outcomes in community living adults attending a 12-week combined lifestyle wellness program.

Methods

A sample of overweight and obese adults (n = 319) and a subgroup who also had diabetes (n = 46 of 319) were studied. The program focuses on dietary, physical activity, and behavioral strategies to promote cardiovascular health. Baseline and 12-week measures were obtained.

Results

In the total sample, all physiological and HRQOL outcomes improved (p < .05), except HDL. High attendance was associated with the highest weight loss. In the diabetic subgroup, weight, steps/day, low density lipoprotein, and most aspects of HRQOL improved significantly.

Conclusion

Physiological and HRQOL benefits can be gained from a 12-week combined lifestyle program; greater benefits were obtained with higher attendance. Although the diabetic subgroup was not large, positive outcomes were realized.

Practice implications

The 12-week combined lifestyle program shows promise for improving outcomes in community living overweight and obese adults who may also be diabetic. By attending class, participants are reminded about strategies they are to apply during the 12-week program and, by program end, they are equipped with a tool kit of strategies for use in everyday life.     

Analysis of demographic and clinical factors affecting the outcome of radioiodine therapy in patients with hyperthyroidism

Introduction

The influence of demographic and clinical factors on the outcome of ¹³¹I therapy in hyperthyroid patients has been examined, based on a retrospective evaluation of results obtained in patients submitted to ¹³¹I treatment at the Department of Nuclear Medicine and Oncological Endocrinology, Medical University of Lodz (Province Hospital, Zgierz). The goal of the study was to analyse such factors as the age and sex of patients, disease duration, as well as the hormonal status before ¹³¹I application, which could have an influence on the effects of therapy with radioiodine ¹³¹I.

Material and methods

The study involved 500 randomly selected patients with hyperthyroidism, treated with ¹³¹I radioiodine. The following 3 groups were defined: group 1 – patients with multinodular goitre (MNG), n = 200; group 2 – patients with a single autonomous nodule of the thyroid (AFTN), n = 100; group 3 – patients with Graves’ disease (GD), n = 200. The local ethics committee (in the Polish Mother''s Memorial Hospital – Research Institute, Lodz) approved the study.

Results

The obtained results indicate that the efficacy of therapy with ¹³¹I applied in patients with MNG, AFTN and GD does not depend on either patient sex or patient age. The length of antithyroid treatment before ¹³¹I therapy onset does not appear to have any effect on the therapy outcome, and the baseline thyrotropin concentration seems to be significant only in the case of GD.

Conclusions

The analysed demographic factors do not affect the outcome of ¹³¹I therapy in hyperthyroidism.     

Inclusion of ALKBH5 as a candidate gene for the susceptibility of autoimmune thyroid disease

PurposeRNA demethylase AlkB homolog 5 (ALKBH5) gene is pivotal in N6-methyladenosine (m6A) modification. Therefore, this study aimed to explore the potential relationship between polymorphisms of ALKBH5 gene and the development of autoimmune thyroid disease (AITD).Material and methodsA case-control study of 979 AITD patients, including 620 Graves' disease (GD) and 359 Hashimoto's thyroiditis (HT), and 732 normal controls of the Chinese Han population was performed using high-throughput sequencing (HiSeq) genotyping method for detecting 5 variants in ALKBH5 gene (rs12936694, rs2124370, rs4925144, rs8068517, and rs9913266). In addition, the associations between ALKBH5 single nucleotide polymorphisms (SNPs) and clinical phenotypes of AITD were investigated.ResultsCompared to normal controls, rs9913266 displayed significant differences in allele and genotype distributions in AITD and GD. rs12936694 also showed significantly different frequencies of alleles in AITD and GD. The link of these 2 loci polymorprhisms to AITD and GD also existed after adjusting for age and gender. When stratified by sex, the minor allele of rs9913266 was associated with the risk of female AITD and HT development before and after adjusting for age and gender. There was a significant association between rs8068517 locus and GD in females after adjusting for the confounders. Finally, we observed significant correlations of haplotypes CGACA and CAGCG to the susceptibility of AITD and GD.ConclusionsOur results provided evidence of association of polymorphisms in ALKBH5 gene with AITD, GD, and HT patients, and hence ALKBH5 might be the candidate gene for susceptibility to AITD.     

Concentraciones de interleucina-18 en preeclámpticas y embarazadas normotensas sanas

Objective

To compare concentrations of interleukin-18 in pre-eclampsia patients and healthy normotensive pregnant women.

Method

A total of 100 patients were selected. Fifty pre-eclamptic patients were selected as cases (group A) and a control group selected by having the same age and body mass index to study group, consisting of 50 healthy normotensive pregnant women. Blood samples were collected in all patients before labour and immediately after diagnosis in group B to determine interleukin-18 concentrations.

Results

There were no significant differences in relation to maternal age, gestation age and body mass index at the time of taking the sample (P = ns). There was a statistically significant difference in interleukin-18 concentrations between patients in cases group (group A; 38.6 ± 6.5 pg/ml) and patients in control group (group B; 32.2 ± 8.5 pg/ml; P < .05). There was a moderate, positive and significant correlation with systolic blood pressure values (r = 0.341; P < .05) and with diastolic blood pressure values (r = 0.408; P < .05).

Conclusions

Pre-eclampsia patients had significantly higher concentrations of interleukin-18 when compared with healthy normotensive pregnant women.     

A usability study of a computerized decision aid to help patients with, early stage papillary thyroid carcinoma in, decision-making on adjuvant radioactive iodine treatment

Objective

We tested the usability of a patient-directed decision aid (DA), intended for patients with early stage papillary thyroid carcinoma (PTC) deciding to accept or reject adjuvant radioactive iodine (RAI) treatment. This decision is complicated by uncertainty of the medical evidence relating to potential treatment benefits.

Methods

The DA was tested by 12 thyroid cancer survivors, 7 thyroid specialty physicians, and 30 lay individuals with no history of thyroid cancer. The participants completed the System Usability Scale for human-computer interaction questionnaire. The medical knowledge of lay participants was assessed before and after DA exposure. Qualitative participant feedback was obtained by thinking aloud during DA use, as well as from interviews.

Results

Participants generally found the usability of the DA acceptable. The DA significantly increased medical knowledge. In spite of some physicians’ concerns about disclosure of treatment controversy and evidence uncertainty, it was found to be acceptable to non-physicians.

Conclusion

A computerized DA on RAI treatment is acceptable to physicians and non-physicians and can improve medical knowledge.

Practice implications

In counseling patients about complex medical decisions, disclosure of uncertainty related to medical evidence may be acceptably conveyed using a DA.     

Pathologic Spectrum of Lymphocytic Infiltration and Recurrence of Papillary Thyroid Carcinoma

Purpose

The aim of this study was to investigate the prognosis of papillary thyroid carcinoma (PTC) patients according to different pathologic grades of lymphocytic thyroiditis (LT).

Materials and Methods

This study included 144 PTC patients who underwent total thyroidectomy with radioactive iodine remnant ablation therapy. Pathologic grades of LT were separated at two points, chronic lymphocytic thyroiditis (CLT) and Hashimoto thyroiditis (HT). Patients were divided into two groupings according to the presence of the diseases (Grouping 1; patients with CLT or HT and without CLT or HT, Grouping 2; patients with HT and without HT). The groupings were compared according to recurrence, clinicopathologic and ultrasound (US) characteristics, and disease free survival.

Results

Of 144 patients, 41 had CLT and 19 had HT. There were 10 patients (6.9%) with tumor recurrence. In both groupings, the presence of calcification was more frequently associated with patients with LT (p=0.041 and 0.047, respectively). In Grouping 2, the mean age at diagnosis was older in patients without HT compared to patients with HT (p=0.032). On multivariate analysis, the presence of LT was not an independent predictor of recurrence in both groupings. For both groupings, pathologic tumor size and taller than wide shape on US were independent predictors of recurrence. The presence of LT in PTC patients did not affect recurrence.

Conclusion

There was no relationship between PTC prognosis and different grades of LT. Pathologic tumor size and taller than wide shape on ultrasound were independent predictors of PTC recurrence regardless of concurrent LT.     

A course for nurses to handle difficult communication situations. A randomized controlled trial of impact on self-efficacy and performance

Objective

To evaluate the impact of a communication skills course for nurses on how to handle difficult communication situations in their daily work.

Methods

A 7-h course was developed using a construct of “Awareness, Feelings, Listen, Solve” (AFLS). A pedagogy of experiential, learner-centered learning was adopted. The course evaluation used a randomized controlled design with pre- and post-measures of self-efficacy and performance.

Results

Forty-one nurses volunteered and thirty-three nurses completed all assigned parts of the study. On self-assessment, there was significant improvement for self-efficacy (F = 24.43, p < 0.001), but not for emotional awareness. On performance, there was no significant improvement between intervention and control groups (F = 3.46, p = 0.073).

Conclusion

A short course for nurses on handling difficult communication situations achieved significant improvements in self-efficacy but not in performance.

Practice implications

Teaching communication skills in community-based settings is important for the safety and effectiveness of patient care. Sponsoring organizations should weigh trade-offs between feasibility and achievement of measurable improvements in performance. One possible approach is to focus on specific communication skills rather than a full suite of skills.     

自身免疫性甲状腺疾病胰岛素样生长因子及其结合蛋白的改变

为探讨胰岛素样生长因子 (IGF )、胰岛素样生长因子结合蛋白 (IGFBP )在自身免疫性甲状腺疾病 (AITD )中的变化及其影响 ,本研究检测了 5 6例AITD患者与 2 4例正常对照血清IGF 1、IGFBP 1～ 3及甲状腺功能 ,发现IGF 1在GD、HT与GD控制组明显低于正常对照 (P <0 0 1) ,IGFBP 1、IGFBP 2在GD组明显高于正常对照 (P <0 0 1,0 0 5 ) ,IGFBP 3在HT组明显低于正常对照 (P <0 0 5 ) ;IGF 1与甲状腺激素间无相关 ,IGFBP 1～ 3均与TT4相关 (r =0 34、 0 38、 0 31;P <0 0 5 )。提示机体甲状腺激素、免疫状态均可能影响IGF、IGFBP水平 ,而后者有可能参与调节AITD的进程。     

Perception of empathy in the therapeutic encounter: effects on the common cold

Objective

To evaluate the effects of patient-practitioner interaction on the severity and duration of the common cold.

Methods

We conducted a randomized controlled trial of 719 patients with new cold onset. Participants were randomized to three groups: no patient-practitioner interaction, “standard” interaction or an “enhanced” interaction. Cold severity was assessed twice daily. Patients randomized to practitioner visits used the Consultation and Relational Empathy (CARE) measure to rate clinician empathy. Interleukin-8 (IL-8) and neutrophil counts were obtained from nasal wash at baseline and 48 h later.

Results

Patients’ perceptions of the clinical encounter were associated with reduced cold severity and duration. Encounters rated perfect on the CARE score had reduced severity (perfect: 223, sub-perfect: 271, p = 0.04) and duration (perfect: 5.89 days, sub-perfect: 7.00 days, p = 0.003). CARE scores were also associated with a more significant change in IL-8 (perfect: mean IL-8 change 1586, sub-perfect: 72, p = 0.02) and neutrophil count (perfect: 49, sub-perfect: 12, p = 0.09).

Conclusions

When patients perceive clinicians as empathetic, rating them perfect on the CARE tool, the severity, duration and objective measures (IL-8 and neutrophils) of the common cold significantly change.

Practice implications

This study helps us to understand the importance of the perception of empathy in a therapeutic encounter.     

Third year medical students perceptions towards learning communication skills: implications for medical education

Objective

To analyze students’ perceptions towards learning communication skills pre-and-post training in a Communication and Clinical Skills Course (CCSC) at a Portuguese Medical School.

Methods

Content analysis was used to describe and systematically analyze the content written by students (n = 215 from a total of 229) in an open-ended survey. In addition, content analysis association rules were used to identify meaning units.

Results

Students’ pre-training definitions of communication skills were not specific; their post-training definitions were more precise and elaborated. Students perceived communications skills in Medicine as important (61%), but recommended that teaching methodologies (52%) be restructured. There appeared to be no connection between criticism of teaching skills performance and perceptions of the other aspects of the course.

Conclusion

Students’ experiences at CCSC are associated with their perceptions of communications skills learning. Content analysis associations indicated that these perceptions are influenced by context.

Practice implications

Improvement of curricula, teaching and assessment methods, and investment in faculty development are likely to foster positive perceptions towards learning communication skills in these students.     

Ciclesonide modulates in vitro allergen-driven activation of blood mononuclear cells and allergen-specific T-cell blasts

Background

Ciclesonide, an inhaled corticosteroid with almost no affinity for the glucocorticoid receptor, is highly effective in downregulating in vitro pro-inflammatory activities of airway parenchymal cells when converted into the active metabolite desisobutyryl-ciclesonide.

Objective

We evaluate whether ciclesonide could effectively downregulate also antigen- or allergen-induced activation of peripheral blood mononuclear cell and of allergen-specific T-cell blasts.

Methods

Peripheral blood mononuclear cells were isolated from non atopic and atopic asthmatic children sensitized to Phleum pratense (PhlP5). Proliferation toward Candida albicans or PhlP5 in the presence of ciclesonide or desisobutyryl-ciclesonide (0.003-3.0 μM) was evaluated as [³H]thymidine incorporation. Modulation of PhlP5-specific T-cell blasts proliferation and PhlP5-induced interleukin 4 expression by ciclesonide and desisobutyryl-ciclesonide were measured.

Results

Peripheral blood mononuclear cell proliferation to C. albicans was dose-dependently inhibited by 0.3-3.0 μM ciclesonide and desisobutyryl-ciclesonide but inhibition by desisobutyryl-ciclesonide was higher. A significant proliferation to PhlP5 was observed only in cultures from atopic subjects: an effective downregulation was already detected at 0.03 μM ciclesonide and 0.003 μM desisobutyryl-ciclesonide (complete inhibition at 3 μM ciclesonide and 0.03 μM desisobutyryl-ciclesonide). 3 μM ciclesonide and desisobutyryl-ciclesonide reduced the PhlP5-specific T-cell blast proliferation and interleukin 4-producing cell proportion.

Conclusions and clinical relevance

These in vitro data, obtained at concentrations similar to those reached in vivo at bronchial level, are in favor of an efficient inhibition of ciclesonide on the T-cell mediated response toward allergens. Additional studies are required to confirm these preliminary data on the reduced activity of the drug on allergen-specific T-cell blast activation that may have clinical relevance.     

A development framework for semantically interoperable health information systems

Background

Semantic interoperability is a basic challenge to be met for new generations of distributed, communicating and co-operating health information systems (HIS) enabling shared care and e-Health. Analysis, design, implementation and maintenance of such systems and intrinsic architectures have to follow a unified development methodology.

Methods

The Generic Component Model (GCM) is used as a framework for modeling any system to evaluate and harmonize state of the art architecture development approaches and standards for health information systems as well as to derive a coherent architecture development framework for sustainable, semantically interoperable HIS and their components. The proposed methodology is based on the Rational Unified Process (RUP), taking advantage of its flexibility to be configured for integrating other architectural approaches such as Service-Oriented Architecture (SOA), Model-Driven Architecture (MDA), ISO 10746, and HL7 Development Framework (HDF).

Results

Existing architectural approaches have been analyzed, compared and finally harmonized towards an architecture development framework for advanced health information systems.

Conclusion

Starting with the requirements for semantic interoperability derived from paradigm changes for health information systems, and supported in formal software process engineering methods, an appropriate development framework for semantically interoperable HIS has been provided. The usability of the framework has been exemplified in a public health scenario.     

The value of training in communication skills for continuing medical education

Objective

Question arises as to what extent communication skills are considered in continuing medical education (CME).

Methods

Analysis for CME-courses in communication skills in the area of the Chamber of Physicians North Rhine (ÄkNo), Germany. Supply Arm(A): CME events (n = 19,320) certified in 2007 were evaluated. Demand Arm(B): course participation of 850 family physicians in the period 2002-2007 was analyzed (n = 37,724). Tests were calculated to the level 0.05 using Mann-Whitney U-test.

Results

(A) 388 (2.0%) events were concerned with the topic communications. 59.3% involved active cooperation of the participants. 0.5% events devoted more than 50% of their duration to the topic communication. Proportions in the subjects of internal medicine, general medicine and pediatrics amounted to 0.2%. (B) 803 (2.1%) events with a focus on communication were identified. Women took part in significantly more events than men (p < 0.002) and selected more interactive courses.

Conclusion

Content on communication training was small. Increasing experience does not automatically improve communication skills but an extent of deliberate praxis seems to be necessary and must be sought and developed.

Practice implications

Communication skills are still insufficiently provided in CME-courses and should be more directed to focus as treatment strategies and scientifically investigated for outcome improvements.     

Graves病和桥本病甲状腺细胞凋亡与Fas表达的研究

为了研究正常、Graves病 (GD )和桥本甲状腺炎 (HT )甲状腺细胞凋亡和凋亡相关蛋白Fas的变化特征及其临床意义 ,采用细胞培养方法和流式细胞术检测正常、GD和HT甲状腺细胞凋亡率和Fas表达量。结果发现 :(1)GD和HT甲状腺细胞凋亡率明显高于正常甲状腺细胞 (P <0 0 1)。其中 ,尤以HT甲状腺细胞凋亡增加最为显著 ;(2 )HT甲状腺细胞Fas表达阳性率明显高于正常和GD甲状腺细胞 (P <0 0 1) ,而GD与正常对照相比无统计学差异。以上结果表明 ,自身免疫性甲状腺疾病 (AITD )患者甲状腺细胞存在细胞凋亡和Fas表达的异常变化 ,尤以HT为显著 ,提示Fas介导的细胞凋亡参与AITD的发病过程 ,可能与HT甲状腺细胞破坏有关。     

Promoting decision aid use in primary care using a staff member for delivery

Objective

To determine the feasibility and effectiveness of in-clinic decision aid distribution using a care assistant.

Methods

We identified potentially eligible patients scheduled for upcoming appointments in our General Internal Medicine Clinic (n = 1229). Patients were deemed eligible for two decision aids: prostate cancer screening and/or weight loss surgery. Patients were approached to view the decision aid in-clinic. Our primary measures were the proportion of decision aids distributed to eligible patients, and the proportion of decision aids viewed.

Results

Among 913 patients who attended their scheduled appointments, 58% (n = 525) were approached and eligibility was assessed by the staff member. Among the 471 who remained eligible, 57% (n = 268) viewed at least a portion of the target decision aid. The mean viewing time for patients who watched less than the complete decision aid was 13 min.

Conclusions

In clinic viewing of decision aids may be a feasible and effective distribution method in primary care.

Practice implications

In clinic distribution requires an electronic health information system to identify potentially eligible patients, and a staff member dedicated to DA distribution. Brief decision aids (less than 10 min) are needed so patients can complete their use prior to the visit to facilitate patient-physician decision making.