bluuebunny/crossref_metadata_2025 huggingface dataset:
Attachment Styles and Outcome of Psychoanalytic Psychotherapy for Children and Adolescents
Authors: Stefini Annette , Horn Hildegard , Winkelmann Klaus , Geiser-Elze Annette , Hartmann Mechtild , Kronmüller Klaus-Thomas
Published: November 2012

Background: Until now few studies have proven that an attachment style can be changed in the course of psychotherapy and that the attachment style has an impact on the therapy outcome. In particular, there is a lack of studies about these relationships in long-term psychoanalytic psychotherapy with children and adolescents. Sampling and Methods: Seventy-one children with mental disorders receiving long-term outpatient psychodynamic psychotherapy were assessed 4 times using the Heidelberg Attachment Style Rating for Children and Adolescents. The measurements were conducted at the beginning of treatment, at the 25th treatment session, at the end of treatment and 1 year after the completion of treatment. Results: The results showed a significant change in attachment style during treatment. The proportion of children and adolescents with a secure attachment style increased from 23% to 63%. There was no significant difference in the attachment style between patients with good and poor treatment outcome, but a significant relationship between secure attachment and the number of treatment sessions could be demonstrated. Conclusions: A reorientation towards a secure main attachment style over the course of psychotherapy is possible. However, attachment style seems to be not a moderator but a mediator for the outcome of psychoanalytic psychotherapy in children and adolescents.
Enhanced Detection of Emotional Facial Expressions in Borderline Personality Disorder
Authors: Schulze Lars , Domes Gregor , Köppen Dürken , Herpertz Sabine C.
Published: November 2012

Background: Borderline personality disorder (BPD) is commonly proposed to be characterized by an enhanced sensitivity for emotional stimuli. In the present study, we investigated whether BPD patients show a superior detection of emotional facial expressions relative to healthy controls. The detection of emotional information in the environment represents an important facet of emotional sensitivity. Sampling and Methods: Twenty patients with BPD were compared with 25 healthy controls. The participants were presented a rapid, continuous stream of neutral and randomly inserted emotional facial expressions and were asked to report the presentation of an emotional facial stimulus after each trial. Availability of cognitive resources was manipulated via two different task demands. Results: The participants with BPD performed significantly better in the detection of positive and negative facial expressions compared to the healthy controls. False alarm rates did not differ significantly between the two groups. Conclusions: The BPD participants showed an enhanced detection of emotional expressions that might be related to the emotional disturbances they experience. In particular, we will discuss the role of this superior emotion detection (in combination with previously reported deficits in the labeling of emotional states) for the understanding of emotional instability in BPD.
Behavioral and Psychological Symptoms of Dementia: Factor Analysis and Relationship with Cognitive Impairment
Authors: Poletti Michele , Nuti Angelo , Cipriani Gabriele , Bonuccelli Ubaldo
Published: November 2012

Background/Aims: Behavioral and psychological symptoms of dementia (BPSD) affect almost all people with dementia at some stage during the progression of disease. The current study aimed at replicating previous findings on BPSD clustering in behavioral sub-syndromes. Methods: One hundred and sixty-six consecutive outpatients with dementia attending a dementia outpatient clinic were enrolled and evaluated with the Neuropsychiatric Inventory and the Mini Mental State Examination. Results: BPSD were reported in 157 patients included in the final sample: 140 patients (89.17%) had Alzheimer’s disease (AD), while 17 patients had frontotemporal dementia or vascular dementia. The most frequent BPSD were depression in the whole sample and irritability in the AD subgroup. The severity of cognitive impairment was predicted by two BPSD in the whole sample (apathy and motor disturbance) and only by nighttime behavior in the AD subgroup. Factor analyses identified 4 factors, accounting for about 60% of variance in the whole group and in the AD subgroup of patients. Conclusions: The current study confirmed findings of previous studies on BPSD clustering, regarding the number of BPSD clusters and the total variance explained. This study has some limitations, including the small number of non-ADs and its monocentric character.
Prognostic Impact of the Charlson Comorbidity Index on Mortality following Acute Pulmonary Embolism
Authors: Ng Austin Chin Chwan , Chow Vincent , Yong Andy Sze Chiang , Chung Tommy , Kritharides Leonard
Published: November 2012

Objectives: It was the aim of this study to determine the prognostic significance of the Charlson Comorbidity Index (CCI) following acute pulmonary embolism (PE) and assess the prognosis of patients without comorbidities (defined as a CCI score of 0). Methods: Outcomes of 1,023 consecutive patients admitted with confirmed PE were tracked after a median of 3.7 years (25-75th interquartile range 1.5-6.1 years). All were assigned a non-age-adjusted CCI score. Results: The median CCI score was 1.0 (interquartile range 0.0-3.0). Three hundred and fifty-one (34%) patients had a CCI score of 0. Only 1 (0.3%) of 31 in-hospital deaths occurred in patients with a CCI score of 0. Long-term mortality for these patients was similar to the population-derived age- and sex-matched mortality rate, and was significantly better than for those with a CCI score ≥1 (12.5 vs. 47.5%; p < 0.0001 adjusted for age and sex). In multivariate analysis, CCI (per 1-score increase) independently predicted in-hospital (hazard ratio 1.27, 95% confidence interval 1.09-1.49; p = 0.003) and post-discharge (hazard ratio 1.35, 95% confidence interval 1.29-1.42; p < 0.0001) death. The c statistics for the multivariate prediction models for in-hospital (incorporating CCI score and serum sodium level) and post-discharge death (age, CCI score, hyperlipidemia, serum sodium and hemoglobin) were 0.738 and 0.788, respectively (both p < 0.0001). Conclusion: The CCI can be incorporated into risk models, with good discriminatory power, for predicting in-hospital and long-term outcomes following acute PE. Patients with a CCI score of 0 have a favorable long-term outcome following acute PE.
Head Position and Expressed Emotion of Adolescents with Schizophrenia and Their Caregivers Compared to Non-Patient Controls
Authors: Ramsauer Brigitte , Lotzin Annett , Parzer Peter , Resch Franz
Published: November 2012

Background: Family interactions with schizophrenia patients and caregivers rated as high expressed emotion (EE) are characterized by increased negative non-verbal behaviour. Head position is one important component of non-verbal behaviour and has not been examined in relation to EE before. The aim of this pilot study was to investigate the influence of caregivers' EE on the head position of adolescents with schizophrenia and their caregivers. Sampling and Methods: 15 adolescent schizophrenia patients and 17 non-patient adolescents were videotaped during a 10-min problem-solving task with their caregiver. The head position was coded by the Berner System of Non-Verbal Behaviour. The caregivers' EE level (high EE vs. low EE) was measured by the Five-Minute Speech Sample. Results: Adolescent patients and non-patients showed a higher frequency of averted head positions towards high EE caregivers compared to low EE caregivers (β = 47.85, t = 2.41, p = 0.023). They displayed longer mean times of averting towards high EE caregivers compared to low EE caregivers (β = -1.78, t = -2.51, p = 0.018). An indirect approach was shown more frequently by adolescent patients towards low EE compared to high EE caregivers (β = 39.99, t = 2.31, p = 0.028). In contrast, non-patient adolescents showed a more indirect approach towards high EE caregivers compared to low EE caregivers. Caregivers of schizophrenia patients had head positions with a straight ahead lowered approach for a longer time compared to caregivers of non-patients (β = -29.75, t = -2.51, p = 0.018). Within the patient and non-patient groups, low EE caregivers showed longer total times of positions with a straight ahead lowered approach than high EE caregivers. Conclusions: High EE communication may be characterized by a higher ratio of averting head position in adolescents, which is especially pronounced in adolescents with schizophrenia. Low EE communication seems to be better adjusted by a more indirect approach being shown by the adolescent and straight ahead lowered head positions by the caregiver, especially when the adolescent suffers from schizophrenia.
Microlesion Effect as a Predictor of the Effectiveness of Subthalamic Deep Brain Stimulation for Parkinson’s Disease
Authors: Tykocki Tomasz , Nauman Paweł , Koziara Henryk , Mandat Tomasz
Published: November 2012

Background: Microlesion effect (MLE) is a commonly observed phenomenon after electrode insertion into the subthalamic nucleus (STN) for deep brain stimulation (DBS). Objectives: The aim of this study was to determine the presence of the MLE in the early postoperative period and the relationship between MLE and STN DBS. Methods: 74 patients with Parkinson’s disease were included in this study. Motor symptoms were evaluated preoperatively, within 48 h after electrode implantation and at 6 months with United Parkinson’s Disease Rating Scale part III (UPDRS-III). According to the improvement level with MLE, all participants were stratified into three groups: (1) less than 20%; (2) 20–40%, and (3) more than 40% in OFF medication states. The degree of improvement in UPDRS-III with DBS ON for each MLE group was assessed at the 6-month follow-up. Regression analysis was applied for the evaluation of the relationship between MLE and improvement with DBS ON. Results: Mean results in UPDRS-III with the MLE in ON and OFF medication states were 22.1 ± 10.5 and 42.1 ± 14 points, respectively. At the 6-month follow-up, with active stimulation, results tended to further ameliorate to 14.6 (59.4%) points in ON and 20.8 (55.3%) in OFF. Mean improvement in MLE groups were: 33.6% group 1, 47.5% group 2 and 61.4% group 3. Regression analysis revealed a positive correlation between the MLE and results at 6 months with DBS ON. Conclusion: Results proved the presence of MLE in the early postoperative period. Furthermore, a positive correlation between MLE and improvement degree with active stimulation was observed.
Neuroimmunomodulatory Alterations in Non-Lesional Peritoneum Close to Peritoneal Endometriosis
Authors: Arnold Julia , Vercellino Giuseppe Filiberto , Chiantera Vito , Schneider Achim , Mechsner Sylvia , Barcena de Arellano Maria Luisa
Published: November 2012

Objectives: An imbalance in the ratio of sensory to sympathetic nerve fibre (NF) density in peritoneal endometriotic lesions (pEL) has recently been demonstrated and leads to the assumption that this preponderance of the sensory pro-inflammatory milieu is a major cause of pain in endometriosis. Therefore, the density of sensory and sympathetic NFs was determined in distal unaffected peritoneum of endometriosis patients to be able to detect possible alterations in unaffected peritoneum. Methods: In serial pEL sections (n = 40), lesional and matching unaffected peritoneum as well as healthy peritoneum (HP) from patients without endometriosis (n = 15) were immunohistochemically analysed to identify protein gene product 9.5-, substance P- and tyrosine hydroxylase-positive NFs (intact, sensory and sympathetic NFs, respectively). In addition, the amount of immune cell infiltrates and the expression of nerve growth factor (NGF) and interleukin (IL)-1β in nerves of peritoneal endometriotic specimens were compared to those in the HP. Results: The overall NF density in the non-lesional, unaffected peritoneum of endometriosis patients is significantly reduced in comparison to both HP and pEL, while sensory NFs remain the same; the sympathetic NF density is significantly decreased compared to HP, but is still higher than the density close to the pEL. Immune cell infiltrates as well as NGF and IL-1β expression in nerves is significantly elevated in distal unaffected peritoneum in comparison to HP. Conclusion: The altered NF density in the non-lesional, unaffected peritoneum of endometriosis patients suggests new aspects in the understanding of the development of endometriosis and pain management in endometriosis.
Thalamotomy as a Treatment Option for Tremor after Ineffective Deep Brain Stimulation
Authors: Bahgat Diaa , Magill Stephen T. , Berk Caglar , McCartney Shirley , Burchiel Kim J.
Published: November 2012

Background: As the number of deep brain stimulation (DBS) surgeries increases, complications from malpositioned electrodes, tolerance to stimulation and loss of efficacy have also increased. Our objective was to assess thalamotomy as a salvage treatment option after ineffective DBS. Methods: A retrospective chart analysis of patients who underwent ipsilateral stereotactic thalamotomy after an ineffective ventrointermediate nucleus DBS procedure was undertaken. Patient outcome was based on follow-up visit chart notes, and a nonvalidated patient telephone questionnaire to assess patients’ perception of tremor and functional ability after thalamotomy. Results: Six patients with essential tremor and 1 with tremor-predominant Parkinson’s disease met our inclusion criteria. Thalamotomies were undertaken for ineffective DBS due to dysarthria and paresthesias with programming in 2 patients, tremor that failed to respond to increased DBS despite a lack of side effects in 2 patients, malpositioned electrode in 2 patients, and sudden loss of DBS efficacy following eye surgery in 1 patient. Following thalamotomy, 3 patients reported improvement in symptoms and function, 3 patients reported improvement in symptoms that were not reflected in functional improvement, and 1 patient reported no improvement in symptoms or function. Conclusion: Thalamotomy may provide a viable salvage solution in patients who fail to respond to DBS due to complications such as malpositioned electrodes, tolerance to stimulation or loss of efficacy.
Cognitive-Behavioral Therapy for Schizophrenia: A Critical Evaluation of Its Theoretical Framework from a Clinical-Phenomenological Perspective
Authors: Škodlar B. , Henriksen M.G. , Sass L.A. , Nelson B. , Parnas J.
Published: November 2012

Background: Cognitive-behavioral therapy (CBT) has played an increasingly important role in psychotherapy for schizophrenia since the 1990s, but it has also encountered many theoretical and practical limitations. For example, methodologically rigorous meta-analyses have recently found only modest overall effect sizes of CBT treatment, and therefore questions have emerged about forwhat and for whom it actually works. Method: The focus of the present paper is to elucidate the theoretical assumptions underlying CBT for schizophrenia and to examine their consistency with abnormalities of experience and self-awareness frequently reported by schizophrenia patients and systematically studied in phenomenological psychopathology from the beginning of the 20th century. Results: We argue that a strong theoretical emphasis on cognitive appraisals with only subsidiary attention devoted to affective and behavioral processes - as is characteristic of many forms of CBT - cannot satisfactorily account for the complex subjective experiences of schizophrenia patients. We further argue that certain theoretical strategies widely employed in CBT to explore and explain mental disorders, which involve atomization and, at times, a reification of mental phenomena, can be problematic and may result in a loss of explanatory potential. Finally, we provide a detailed account of how negative symptoms and delusions are conceptualized in CBT and consider the question of how these concepts fit the actual phenomenology of schizophrenia. Conclusion: We suggest that further advancement of CBT theory and practice can benefit from a dialogue with phenomenological psychiatry in the search for effective psychotherapeutic strategies for schizophrenia patients.
Mitochondrial DNA Damage Mediates Hyperoxic Dysmorphogenesis in Rat Fetal Lung Explants
Authors: Gebb Sarah A. , DeCoux Ashley , Waggoner Alicia , Wilson Glenn L. , Gillespie Mark N.
Published: November 2012

Background: Numerous studies in cultured cells indicate that damage to mitochondrial DNA (mtDNA) dictates cellular responses to oxidant stress, yet the consequences of mtDNA damage have not been studied directly in the preterm lung. Objective: We sought to determine whether hyperoxia-induced fetal lung dysmorphogenesis is linked to mtDNA damage and establish mtDNA repair as a potential therapeutic approach for treating lung dysplasia in the preterm neonate. Methods: Hyperoxia-induced mtDNA damage was assessed by quantitative alkaline gel electrophoresis in normoxic (3% O2) and hyperoxic (21% O2) fetal rat lung explants. A fusion protein construct targeting the DNA repair enzyme endonuclease III (Endo III) to the mitochondria was used to augment mtDNA repair. Fetal lung branching and surfactant protein C (SFPTC) were assessed in these tissues. Results: Hyperoxia induced mtDNA damage in lung explants and was accompanied by impaired branching morphogenesis and decreased SFPTC mRNA expression. Treatment of lung explants with Endo III fusion protein prevented hyperoxia-induced mtDNA damage and restored normal branching morphogenesis and SFPTC mRNA expression. Conclusion: These findings support the concept that mtDNA governs cellular responses to oxidant stress in the fetal lung and suggest that modulation of mtDNA repair is a potential pharmacologic strategy in the prevention of hyperoxic lung injury.
Impact of Thyrotropin Receptor Antibody Levels on Fetal Development in Two Successive Pregnancies in a Woman with Graves’ Disease
Authors: Bjørgaas Marit R. , Farstad Hanne , Christiansen Sverre C. , Blaas Harm-Gerd K.
Published: November 2012

Background: Treatment with radioiodine for Graves’ disease regularly increases the level of antithyroid antibodies, and transplacental passage of stimulating thyrotropin receptor antibodies (TRAb) may cause fetal hyperthyroidism. Case presentation: A 21-year-old woman with Graves’ disease received radioiodine treatment to avoid use of antithyroid drugs in pregnancy. She became pregnant 4 months later and was euthyroid during pregnancy. In gestational week (GW) 33, she was admitted with an increased fetal heart rate of 176–180 beats/min. Fetal echocardiography indicated cardiac decompensation. The neonate had severe hyperthyroidism (free thyroxine >100 pmol/l, nv 12.0–22.0), cardiac insufficiency, insufficient weight gain, goiter and considerably accelerated skeletal age. In the mother and neonate, TRAb was >40 IU/l (nv <1.0), indicating transplacental passage of stimulating antibodies. After delivery, TRAb remained >40 IU/l in the woman, and 18 months later she underwent total thyroidectomy with subsequent decline in TRAb. In her next pregnancy, TRAb fluctuated between 38 and 17 IU/l, and repeated fetal ultrasound showed no goiter or sign of hyperthyroidism. In cord blood, TRAb was 10.9 IU/l, and the neonate had normal thyroid hormone levels. Conclusion: This case report illustrates the impact of maternal TRAb level for neonatal outcome in two successive pregnancies.
Efficacy, Safety, and Survival Factors for Sorafenib Treatment in Japanese Patients with Advanced Hepatocellular Carcinoma
Authors: Nakano Masahito , Tanaka Masatoshi , Kuromatsu Ryoko , Nagamatsu Hiroaki , Sakata Kenji , Matsugaki Satoru , Kajiwara Masahiko , Fukuizumi Kunitaka , Tajiri Nobuyoshi , Matsukuma Norito , Sakai Terufumi , Ono Noriyuki , Yano Yoichi , Koga Hironori , Kurogi Junichi , Takata Akio , Sumie Shuji , Satani Manabu , Yamada Shingo , Niizeki Takashi , Aino Hajime , Iwamoto Hideki , Torimura Takuji , Sata Michio ,   for the Kurume Liver Cancer Study Group of Japan
Published: November 2012

Background: Sorafenib, an oral multikinase inhibitor, was approved for the treatment of advanced hepatocellular carcinoma (HCC), but has not been adequately evaluated for safety and effectiveness in Japanese patients with advanced HCC. Aims: The purpose of this study was to prospectively assess the efficacy, safety, and risk factors for survival in patients with advanced HCC treated with sorafenib. Methods: Between May 2009 and December 2010, 96 Japanese patients with advanced HCC (76 male, 20 female, mean age: 70.4 years) were treated with sorafenib. Eighty-eight patients had Child-Pugh class A, and 8 patients had Child-Pugh class B liver cirrhosis. Barcelona Clinic Liver Cancer stage B and C were found in 64 and 32 patients, respectively. Results: Twelve patients demonstrated partial response to sorafenib therapy, 43 patients had stable disease, and 33 patients had progressive disease at the first radiologic assessment. The most frequent adverse events leading to discontinuation of sorafenib treatment were liver dysfunction (n = 8), hand-foot skin reaction (n = 7), and diarrhea (n = 4). The median survival time and time to progression were 11.6 and 3.2 months, respectively. By multivariate analysis, des-γ-carboxy prothrombin serum levels and duration of treatment were identified as independent risk factors for survival. Conclusions: This study showed that sorafenib was safe and useful in Japanese patients with advanced HCC. In addition, this study demonstrated that sorafenib should be administered as a long-term treatment for advanced HCC regardless of therapeutic effect and dosage.
Improvement in Hematopoiesis after Iron Chelation Therapy with Deferasirox in Patients with Aplastic Anemia
Authors: Lee Sung-Eun , Yahng Seung-Ah , Cho Byung-Sik , Eom Ki-Sung , Kim Yoo-Jin , Lee Seok , Min Chang-Ki , Kim Hee-Je , Cho Seok-Goo , Kim Dong-Wook , Min Woo-Sung , Park Chong-Won , Lee Jong Wook
Published: November 2012

Iron overload due to regular transfusions of packed red cells can cause multiple organ damage. Iron chelation therapy (ICT) is important in patients with aplastic anemia (AA) who require blood transfusions as supportive management. With the introduction of the oral iron chelator deferasirox, ICT has become more widely available and feasible. We studied 4 adult AA patients who had transfusion-induced iron overload and showed hematological improvement after ICT with oral deferasirox. Following deferasirox treatment, hemoglobin increased and serum ferritin levels decreased, and the patients subsequently became transfusion independent. Our experience raises the possibility of the potential benefit of ICT on hematopoiesis. Further long-term studies in larger patient cohorts are needed to clarify the effect of the restoration of hematopoiesis after iron chelation therapy.
Cocktail Blood Biomarkers: Prediction of Clinical Outcomes in Patients with Acute Ischemic Stroke
Authors: Zeng Lili , Liu Jianrong , Wang Yongting , Wang Ling , Weng Suiqing , Chen Shengdi , Yang Guo-Yuan
Published: November 2012

Background: Timely prediction of stroke outcomes is important for proper personalized treatment. In the present study, we aimed to develop cocktail blood biomarkers to increase prediction efficiency using a combination of hemostasis, inflammatory and repair-related biomarkers. Methods: 105 patients suffering from acute ischemic stroke were divided into good outcome group and poor outcome group by modified Rankin Scale (mRS). Cytokines including CD40L, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-17 and TNF-α, as well as hemostasis markers fibrinogen, fibrin degradation products (FDP), D-dimer, tissue plasminogen activator, and plasminogen activation inhibitor-1 in plasma were examined by ELISA. Repair-related biomarker microRNA-210 (miR-210) was measured by real-time PCR. The prediction efficiency was explored by receiver operator characteristic analysis. Results: We demonstrated that FDP, IL-6 and miR-210 levels were closely associated with mRS in stroke patients. The prediction sensitivity of FDP, IL-6 and miR-210 for stroke outcome was 72.0, 86.7 and 82.5%, respectively. Using a combination of biomarkers including FDP, IL-6 and miR-210, the prognostic sensitivity of ischemic stroke increased to 95.2%. Conclusion: The combination of FDP, IL-6 and miR-210 has a high sensitivity for predicting stroke recovery, it serves as a potential cocktail blood biomarker. It provides a novel approach for stroke prognosis.
The Evolution of Technological Strategies in the Prevention of Dialysis Water Pollution: Sixteen Years’ Experience
Authors: Bolasco Piergiorgio , Contu Antonio , Meloni Patrizia , Vacca Dorio , Murtas Stefano
Published: November 2012

Aim: This report attempts to illustrate the positive impact on the quality of dialysis water produced over a 16-year period through the progressive optimization of technological procedures. Methods: Fundamental steps included the following: elimination of polyvinyl chloride (PVC), periodical controls, introduction of stainless steel and/or polyethylene polymer and substitution of single-pass reverse osmosis (SRO) with double-pass reverse osmosis (DRO). Daily overnight automatic thermal disinfection of distribution piping rings represented the final step. Results: A dramatic improvement was observed in 645 water samples obtained from distribution piping. The measures applied resulted in a significant improvement of water quality, featuring levels of colony-forming units per milliliter ranging from 247.4 ± 393.7 in the presence of PVC and SRO to 14.1 ± 28.0 with stainless steel and DRO and 2.8 ± 3.2 with cross-linked polyethylene thermoplastic polymer and DRO (p < 0.01). Conclusions: Dialysis water should be viewed by nephrologists as a medicinal product, and every effort should be made to ensure a high-quality liquid.
Hydroxychloroquine-Induced Cardiomyopathy That Presented as Pulmonary Hypertension: A Newly Noted Complication
Authors: Bae Sang Mook , Jung Hae Ok , Ihm Sung Min , Kim Jin Jin , Chin Jung Yeon , Kim Tae-Seok , Park Sung Hwan , Youn Ho-Joong , Lee Kyo Young
Published: November 2012

We examined a 63-year-old woman with progressive dyspnea. Two years prior to admission to our hospital, she had been diagnosed with rheumatoid arthritis and treated with hydroxychloroquine (HCQ) with a cumulative dose of 164 g. In addition, 2 months earlier, she had been diagnosed with connective tissue disease-related pulmonary artery hypertension. We performed an electrocardiogram and noted complete atrioventricular block. A transthoracic echocardiogram showed pulmonary hypertension. Due to the unclear nature of the pulmonary hypertension, we performed cardiac catheterization and right ventricular endomyocardial biopsy. Cardiac catheterization revealed that pulmonary hypertension was due to left ventricular dysfunction. Electron microscopy of the cardiac biopsy demonstrated a curvilinear body, diagnostic of HCQ toxicity. Thus, we diagnosed pulmonary hypertension owing to left heart disease and complete atrioventricular block that resulted from HCQ toxicity. Insertion of a permanent pacemaker and discontinuation of HCQ dramatically improved the disease state. This is the first report of this type of cardiac complication with HCQ; it raises the awareness that HCQ may cause cardiac complications despite a small cumulative dose relative to doses reported in other cases. Furthermore, we emphasize that cardiac catheterization played a critical role in the differential diagnosis from pulmonary hypertension associated with connective tissue disease.
Expression of Nogo-A Is Decreased with Increasing Gestational Age in the Human Fetal Brain
Authors: Haybaeck J. , Llenos I.C. , Dulay R.J. , Bettermann K. , Miller C.L. , Wälchli T. , Frei K. , Virgintino D. , Rizzi M. , Weis S.
Published: November 2012

Nogo is a member of the reticulon family. Our understanding of the physiological functions of the Nogo-A protein has grown over the last few years, and this molecule is now recognized as one of the most important axonal regrowth inhibitors present in central nervous system (CNS) myelin. Nogo-A plays other important roles in nervous system development, epilepsy, vascular physiology, muscle pathology, stroke, inflammation, and CNS tumors. Since the exact role of Nogo-A protein in human brain development is still poorly understood, we studied its cellular and regional distribution by immunohistochemistry in the frontal lobe of 30 human fetal brains. Nogo-A was expressed in the following cortical zones: ependyma, ventricular zone, subventricular zone, intermediate zone, subplate, cortical plate, and marginal zone. The number of positive cells decreased significantly with increasing gestational age in the subplate and marginal zone. Using different antibodies, changes in isoform expression and dimerization states could be shown between various cortical zones. The results demonstrate a significant change in the expression of Nogo-A during the development of the human brain. The effects of its time- and region-specific regulation have to be further studied in detail.
Long-Term Changes in the Personality and Psychopathological Profile of Opiate Addicts after Nucleus Accumbens Ablative Surgery Are Associated with Treatment Outcome
Authors: Ge Shunnan , Chang Chongwang , Adler John R. , Zhao Haikang , Chang Xiaozan , Gao Li , Wu Heming , Wang Jing , Li Nan , Wang Xuelian , Gao Guodong
Published: November 2012

Objective: To investigate the long-term outcome and changes of the personality and psychopathological profile of opiate addicts after bilateral stereotactic nucleus accumbens (NAc) ablative surgery. Methods: 60 patients were followed up for 5 years and abstinent status and adverse events were evaluated. NAc lesion volumes and locations were obtained by postoperative MRI scans. The Chinese version of the Eysenck Personality Questionnaire (EPQ-RSC), the Symptom Checklist-90-Revised (SCL-90-R), the Beck Depression Inventory (BDI), the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the World Health Organization’s Quality of Life Questionnaire – Brief Version (WHOQOL-BREF) were administered to the patients before and 5 years after the stereotactic surgery. Results: The total abstinence rate of all patients in their 5th postoperative year was 47.4%. The abstinent patients had a significantly larger lesion volume than the relapsed ones, but a larger lesion volume also increased the risk of adverse events. 5 years after surgery, the abstinent patients showed significant decreases on the Psychoticism (EPQ-P) and Neuroticism (EPQ-N) scores by EPQ-RSC, a significant decline on the Global Severity Index and the subscores in all 10 dimensions by SCL-90-R, significant decreases on the BDI and Y-BOCS scores, and significant improvements on the scores of all domains by WHOQOL-BREF, while for the relapsed patients, only the subscores of obsessive-compulsive by SCL-90-R and the Y-BOCS scores significantly decreased. Postoperative analysis revealed that the abstinent patients had a significantly better score than the relapsed ones by various instruments, and NAc lesion volumes and locations did not correlate with the outcome of any of these instruments. Conclusion: The bilateral ablation of NAc by stereotactic neurosurgery was a feasible method for alleviating psychological dependence on opiate drugs and preventing a relapse. Long-term follow-up suggested that surgery can improve the personality and psychopathological profile of opiate addicts with a trend towards normal levels, provided persistent abstinence can be maintained; relapse, on the other hand, may ruin this effect.
Maternal Serum Soluble Endoglin at 30-33 Weeks in the Prediction of Preeclampsia
Authors: Lai Jonathan , Syngelaki Argyro , Poon Leona C.Y. , Nucci Marta , Nicolaides Kypros H.
Published: November 2012

Objective: To investigate the potential value of maternal serum concentration of soluble endoglin (sEng) at 30-33 weeks' gestation in the prediction of preeclampsia (PE) developing at or after 34 weeks. Methods: Serum sEng was measured at 11-13 and at 30-33 weeks' gestation in a case-control study of 50 cases that developed PE at or after 34 weeks and 250 unaffected controls. Regression analysis was used to determine which of the factors amongst the maternal characteristics were significant predictors of first- and third-trimester log10 sEng in the control group. The measured values of sEng were converted into multiples of the unaffected median (MoM) and the MoM values in the PE and controls were compared. Results: The median sEng MoM at 30-33 weeks was significantly higher in the PE group (1.39, IQR 0.94-2.18) than in the controls (0.95, IQR 0.77-1.19), but at 11-13 weeks there was no significant difference between the groups. In screening by a combination of maternal characteristics and third-trimester sEng, the detection rates of intermediate- and late-PE, at a false-positive rate of 10%, were 64.3 and 50.0%, respectively. Conclusion: Screening by maternal characteristics and sEng at 30-33 weeks could identify most pregnancies that will subsequently develop PE.
Plaque Characteristics of Asymptomatic Carotid Stenosis and Risk of Stroke
Authors: Mono Marie-Luise , Karameshev Alexander , Slotboom Johannes , Remonda Luca , Galimanis Aekaterini , Jung Simon , Findling Oliver , De Marchis Gian Marco , Luedi Rudolf , Kiefer Claus , Stuker Carole , Mattle Heinrich P. , Schroth Gerhard , Arnold Marcel , Nedeltchev Krassen , El-Koussy Marwan
Published: November 2012

Background: The optimal treatment of asymptomatic carotid stenosis (ACS) is controversial. To optimize the risk-benefit ratio of carotid artery revascularization, it is crucial to identify ACS patients who are at increased stroke risk. Recent data suggest that plaque vulnerability depends on its composition. Therefore, we assessed plaque composition in ACS to determine predictors for ipsilateral cerebrovascular events. Methods: 62 patients with 65 ACS ≥50% underwent 3-T MRI of the carotid bifurcation (TOF, special dark-blood weighted noncontrast and contrast-enhanced T1 and T2 images) and of the brain. The different plaque components (lipid core, intraplaque hemorrhage, calcification and the status of the fibrous cap) were assessed. Furthermore, the plaque volume and the volume of clinically silent cortical and subcortical infarcts in the territory of the stenosed carotid artery as seen on FLAIR images were determined by using a semi-automated software. Carotid stenosis was considered asymptomatic if there had not been any clinically apparent ischemic events in the corresponding vascular territory within the previous 6 months. During follow-up, information on the occurrence of cerebrovascular events, medical treatment and sonographic changes of the stenosis was collected. Results: At baseline, 24 ACS (37%) were classified as high grade. A lipid-rich necrotic core was the dominant plaque component in 16 ACS (25%). The plaque volume was higher in ACS with a lipid-rich necrotic core as dominant plaque component (p = 0.002) and in patients with prior stroke/TIA (p = 0.010). After a median follow-up of 18.9 months (interquartile range 3.5–30.1) there were 2 ipsilateral strokes and 3 ipsilateral TIAs. The average annual event rate was 7.7%. A lipid-rich necrotic core (HR 7.21; 95% CI 1.12–46.28; p = 0.037), sonographic progression of the stenosis (HR 7.00; 95% CI 1.13–41.34; p = 0.036), history of stroke (HR 11.03; 95% CI 1.23–99.36; p = 0.032), and the volume of clinically asymptomatic ischemic brain lesions (HR 1.14/cm3; 95% CI 1.03–1.25; p = 0.008) predicted cerebrovascular events. Patients on statin therapy at follow-up were at lower risk of events (HR 0.17; 95% CI 0.03–1.00; p = 0.05). Conclusions: In addition to medical history and sonographic findings, a lipid-rich necrotic core within the plaque turned out as a predictor of cerebrovascular events. Therefore, MR imaging of carotid plaques deserves further attention and might be helpful to improve risk stratification of asymptomatic carotid disease. The identified predictors could be combined in a risk model and tested in larger prospective studies.
The Polyketide Synthase-Associated Multidrug Tolerance in Mycobacterium intracellulare Clinical Isolates
Authors: Matsunaga Isamu , Meda Shinji , Nakata Noboru , Fujiwara Nagatoshi
Published: November 2012

Background: Intrinsic multidrug resistance of the Mycobacterium avium-intracellulare complex presents a serious problem in the treatment of the diseases caused by these bacteria. Recently, it was shown that deletion of a polyketide synthase, Pks12, in an M. avium laboratory strain decreases this intrinsic resistance. Methods: We investigated Pks12 expression and its enzymatic activity in 9 clinical isolates of M. intracellulare, and compared their drug susceptibilities to 4 drugs. Also, we made pks12-disrupted M. bovis bacillus Calmette-Guérin (BCG) mutant and its complemented strain. Using these BCG and M. intracellulare strains, we observed intracellular accumulation of ethidium bromide (EtBr). Results: We found positive correlations between Pks12 and drug resistance for all of the antibiotics tested. The drug susceptible M. intracellulare strain showed higher EtBr accumulation. Consistent with this, EtBr was much more accumulated in pks12-disrupted BCG than wild-type or the complemented strains. Conclusions: Collectively, these results suggest that Pks12 controls the multidrug resistance in part through intracellular drug accumulation.
The Screening of Methicillin-Resistant Staphylococcus aureus in Vascular Surgery Patients: A Comparison of Molecular Testing and Broth-Enriched Culture
Authors: Fiolic Zlatko , Bosnjak Zrinka , Snajdar Irena , Crkvenac Gregorek Andrea , Kalenic Smilja , Budimir Ana
Published: November 2012

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a major global health care-associated pathogen. This study sought to examine the prevalence of MRSA in patients who were admitted to a vascular surgery ward during a 3-month period. Methods: MRSA screening was accomplished through the acquisition of nasal, throat and perineal swabs. These swabs were placed in tryptic soy broth that had been supplemented with 6.5% NaCl and incubated for 24 h. The resulting isolates were subcultured on agar plates containing 5% sheep blood. The BD GeneOhm MRSA assay for screening swabs was performed in accordance with the manufacturer’s instructions. Results: A total of 58 patients were included in the study and swabs from 232 sites were obtained during the sampling period. MRSA was detected in 33 samples of 12 patients during the study period; thus, there was a 20.6% prevalence of patients who were recognized as MRSA carriers. There were discrepancies between the results of classical bacteriological screening and molecular MRSA detection methods in 8 of the patients. Conclusions: Nasal, throat and perineal MRSA screening can detect the carriage of this pathogen and allow for the timely use of appropriate infection control measures. The choice of screening techniques poses a challenge; it has been demonstrated that molecular detection methods should be performed with great sensitivity, specificity and, most importantly, speed. The cost of the PCR screening method is the only disadvantage of this approach.
Pyoderma Gangrenosum, Acne and Suppurative Hidradenitis Syndrome following Bowel Bypass Surgery
Authors: Marzano Angelo V. , Ishak Rim S. , Colombo Antonella , Caroli Francesco , Crosti Carlo
Published: November 2012

The clinical triad of pyoderma gangrenosum (PG), acne and suppurative hidradenitis (PASH) has recently been described as a new disease entity within the spectrum of autoinflammatory syndromes, which are an emerging group of inflammatory diseases distinct from autoimmune, allergic and infectious disorders. PASH syndrome is similar to PAPA (pyogenic arthritis, acne and PG), but it differs in lacking the associated arthritis and on a genetic basis. PAPA syndrome is caused by mutations in a gene involved in the regulation of innate immune responses, the PSTPIP1, while no mutations have been detected to date in patients with PASH syndrome. We report a young male patient who developed coexisting disseminated PG, typical suppurative hidradenitis and acneiform eruption on the face, after he had undergone bowel bypass surgery for obesity. The cutaneous manifestations associated with bowel bypass syndrome often mimic PG or other neutrophilic dermatoses, suggesting a pathogenesis related to neutrophil-mediated inflammation for this condition. This is the first report describing PASH syndrome after bariatric surgery, and we propose to include such neutrophilic dermatoses in the list of complications occurring after bowel bypass surgery. Extensive genetic studies may help to clarify the etiopathogenesis of PASH as well as of autoinflammatory diseases in general.
Treating the Small Airways
Authors: Usmani Omar S.
Published: November 2012

The final article in this series evaluates the approaches undertaken to treating the small-airway region of the lungs and the clinical implications of inhaled therapy targeting the periphery in patients with asthma and chronic obstructive pulmonary disease.
Challenging False Discovery Rate: A Partition Test Based on p Values in Human Case-Control Association Studies
Authors: Ott Jurg , Liu Zhe , Shen Yuanyuan
Published: November 2012

Background/Aims: We consider the situation that multiple genetic variants are underlying a heritable trait and assume that each contributes to the trait only to a small degree. The aim is to develop a statistical test for disease association of these multiple variants. Methods: We expect that p values resulting from a genome-wide case-control association analysis will fall into two classes: those reflecting true association and those occurring randomly in the interval from 0 to 1. We develop a partition test to find the set of smallest p values deviating most from the number of p values expected under randomness. Results: Power calculations demonstrate the superiority of our partition test over conventional SNP-by-SNP analyses. Applications of the partition test to six published datasets show that our test is particularly suitable when multiple SNPs appear to contribute to a trait, and furnished more significant results than a well-known procedure to estimate the false discovery rate. Conclusions: Our partition test also furnishes an estimate of the number of functional SNPs underlying disease and can be highly significant, while single-locus tests may be far from significant.
Comparison of the Effects of Electrical Stimulation and Posterior Tibial Nerve Stimulation in the Treatment of Overactive Bladder Syndrome
Authors: Gungor Ugurlucan Funda , Onal Murat , Aslan Ergul , Ayyildiz Erkan Habibe , Kizilkaya Beji Nezihe , Yalcin Onay
Published: November 2012

Aim: To compare the effects of transvaginal electrical stimulation (ES) and posterior tibial nerve stimulation (PTNS) in the treatment of overactive bladder syndrome (OAB). Methods: Women applying with symptoms of urgency, frequency, and nocturia with or without incontinence and diagnosed with OAB were divided into an ES or PTNS group. Bladder diary, urodynamics, 1-hour pad test, and King’s Health Questionnaire were performed before and after treatment. ES was applied for 20 min, 6–8 weeks with pulses of 10–50 Hz square waves at a 300-µs or 1-ms pulse duration and a maximal output current of 24–60 mA with 5–10 Hz frequency, three times per week. PTNS was applied for 30 min once a week for 12 weeks. Results: Thirty-five patients received ES, 17 patients received PTNS. Pad test, urinary diary, and quality of life parameters after both treatments decreased significantly; the decrease in the ES group was greater. The number of patients who describe themselves as cured was higher in the ES group. Conclusion: PTNS and ES are both effective in the treatment of OAB with significant improvement in objective and subjective parameters. Objective results show no significant difference between the two groups; however, the number of patients who describe themselves as cured in the ES group was significantly higher.
Reduction of Miscarriages through Universal Screening and Treatment of Thyroid Autoimmune Diseases
Authors: Lepoutre Thibault , Debiève Frederic , Gruson Damien , Daumerie Chantal
Published: November 2012

Background/Aims: Universal screening for thyroid diseases during pregnancy is controversial. Targeted screening does not identify all women with thyroid dysfunction. Furthermore, antithyroid peroxidase antibodies (TPOAb) are suspected to be associated with an increased risk of fetal loss, premature delivery and hypothyroidism. The aim of our study was to assess the rationale behind universal screening and propose thyroxine treatment in particular cases. Methods: Between January 2008 and May 2009, 537 consecutive iodine-supplemented women with a singleton pregnancy [441 TPOAb– controls and 96 TPOAb+ women (47 nontreated and 49 treated)] were evaluated using thyroid and obstetric parameters. According to our algorithm for thyroid screening in pregnancy, if thyroid-stimulating hormone (TSH) exceeded 1 mU/l in TPOAb+ women, 50 µg of levothyroxine (L-T4) was prescribed. Results: The miscarriage rate was significantly higher in the nontreated TPOAb+ group compared with the treated group (16 vs. 0%; p = 0.02). Compared to the control group, TSH in TPOAb+ patients was higher at the first prenatal visit prior to L-T4 treatment (p < 0.01), while free thyroxine was higher than in the control group after the 20th week (p < 0.05). Conclusions: Our study supports the potential benefit of universal screening and L-T4 treatment for autoimmune thyroid disease during pregnancy. Efforts are still needed to further decrease miscarriage rates.
An Optimum Projection and Noise Reduction Approach for Detecting Rare and Common Variants Associated with Complex Diseases
Authors: Turkmen Asuman , Lin Shili
Published: November 2012

Background: Despite the thrilling advances in identifying gene variants that influence common diseases, most of the heritable risk for many common diseases still remains unidentified. One of the possible reasons for this missing heritability is that the genome-wide association study (GWAS) approaches have been focusing on common rather than rare single nucleotide variants (SNVs). Consequently, there is currently a great deal of interest in developing methods that can interrogate rare variants for association with diseases. Methods: We propose a two-step method (termed rPLS) to reveal possible genetic effects related to rare as well as common variants. The procedure starts with removing irrelevant variants using penalized regression (regularization) which is followed by partial least squares (PLS) on the surviving SNVs to find an optimal linear combination of rare and common SNVs within a genomic region that is tested for its association with the trait of interest. Results: Simulation settings based on the 1000 Genomes sequencing data and reflecting real situations demonstrated that rPLS performs well compared to existing methods especially when there are a large number of noncausal variants (both rare and common) present in the gene and when causal SNVs have different effect sizes and directions.