bluuebunny/crossref_metadata_2025 huggingface dataset:
Herpes Viral Origin of the Parsonage-Turner Syndrome: Highlighting of Serological Immune Anti-Herpes Deficiency Cured by Anti-Herpes Therapy
Authors: Le Goaster Jacqueline , Bourée Patrice , Ifergan Charles , Tangy Frederic , Olivier René , Haenni Anne-Lise
Published: June 2015

In 2012, a 50 year-old athletic male presented with weakness, pain and unilateral phrenic paralysis, followed by bilateral phrenic paralysis with deep dyspnea. In 2013, the Parsonage-Turner syndrome was diagnosed. When the patient was seen in September 2014 for the first time, he was facing phrenic neuromuscular failure, which led to the hypothesis of neurotropic herpes viruses. A control of the global serological anti-Herpes immunity to analyze his antibody (Ab) levels confirmed herpes immune genetic deficiency. An appropriate herpes chemotherapy treatment was proposed. Immediately, a spectacular recovery of the patient was observed, and after a few weeks, the respiratory function tests showed normal values. The hypothesis of the inductive role of viruses of the herpes family in the Parsonage-Turner syndrome was thus substantiated. The patient's immune deficiency covers the HSV2, HHV3, HHV4, HHV5 and HHV6 Ab levels. This led to the control of herpes in the family lineage: indeed, his daughter presented alterations of her serological herpes Ab levels.
Endothelial Repair in Childhood Arterial Ischaemic Stroke with Cerebral Arteriopathy
Authors: Eleftheriou Despina , Ganesan Vijeya , Hong Ying , Klein Nigel J. , Brogan Paul A.
Published: June 2015

Background: We have previously shown that recurrent arterial ischaemic stroke (AIS) in children with cerebral arteriopathy is associated with increased circulating endothelial cells and endothelial microparticles, consistent with ongoing endothelial injury. To date, however, little is known about endothelial repair responses in childhood AIS. We examined the relationship between the number and function of circulating endothelial progenitor cells (EPC), the levels of brain-derived neurotrophic factor (BDNF) and AIS recurrence. Methods: Flow cytometry was used to identify peripheral blood mononuclear cells positive for CD34/kinase insert domain-containing receptor (KDR). In a subgroup of patients (5 in each group selected at random), monocytic EPC function was assessed by colony-forming unit (EPC-CFU) capacity and incorporation into endothelial cell networks in Matrigel. BDNF was measured using ELISA. Results: Thirty-five children, aged 12 years (range: 5-16.5; 9 males), with AIS and cerebral arteriopathy were studied; 10 had recurrent AIS. CD34+/KDR+ cells were significantly higher in recurrent AIS compared to non-recurrent AIS patients (p = 0.005) and controls (p = 0.0002). EPC-CFU and EPC incorporation into endothelial cell networks were significantly reduced in recurrent compared to non-recurrent AIS patients (p = 0.04 and p = 0.01, respectively). Levels of BDNF were significantly higher in recurrent compared to non-recurrent AIS patients (p = 0.0008) and controls (p = 0.0002). Conclusions: Children with recurrent AIS and cerebral arteriopathy had increased circulating CD34+/KDR+ cells and BDNF consistent with an endothelial repair response. However, EPC function was impaired. Future studies are needed to examine whether suboptimal endothelial repair contributes to childhood AIS recurrence.
Serotonin Syndrome in a Patient on Trazodone and Duloxetine Who Received Fentanyl following a Percutaneous Liver Biopsy
Authors: Gaffney Ryan R. , Schreibman Ian R.
Published: June 2015

Serotonin syndrome is a rare but potentially life-threatening adverse drug reaction resulting from the use or overuse of serotonergic medications alone or in combination. Mild symptoms, overlapping features with similar conditions and clinician lack of awareness are the major reasons for an often missed diagnosis. Not surprisingly, this condition is significantly underreported as a potential complication of endoscopy if serotonergic medications are used periprocedurally for sedation and analgesia. Here we report the case of a patient with relapsed chronic hepatitis C on antidepressant medications who developed signs and symptoms of serotonin syndrome after a percutaneous liver biopsy. Review of the patient's medication list suggested a possible interaction between her home antidepressants and the post-procedure use of fentanyl for abdominal pain. The patient required monitoring in the medical intensive care unit and stabilized after the administration of benzodiazepines and temporary discontinuation of her home medications. We propose that clinicians need to be aware of the increased risk of serotonin syndrome in the outpatient endoscopy setting, particularly with the wider use of serotonergic antidepressants now available and the repeated number of liver biopsies being performed for management of patients with chronic liver disease.
Complete Endoscopic Submucosal Dissection of a Giant Rectal Villous Adenocarcinoma with Electrolyte Depletion Syndrome
Authors: Kure Kazumasa , Kawai Masaya , Ishiyama Shun , Kamiyama Hirohiko , Tomiki Yuichi , Sakamoto Kazuhiro , Arakawa Atsushi , Yao Takashi
Published: June 2015

An 81-year-old female consulted a local physician due to diarrhea. Since general fatigue and body weight loss were observed, she was admitted for detailed examination and treatment. Colonoscopy revealed a circumferential giant tumor with a maximum diameter of 10 cm in the rectum, and biopsy findings indicated villous adenoma. The tumor secreted a large amount of mucus, and a diagnosis of electrolyte depletion syndrome causing electrolyte disorders was made. We performed endoscopic submucosal dissection (ESD) as a less invasive procedure. The tumor was so big that the procedure had to be completed in two separate steps and it took 1,381 min in total. The tumor was histologically diagnosed as well-differentiated adenocarcinoma in high-grade adenoma located in the lower to upper rectum, invading into the mucosa without lymphatic or venous invasion. The stump of the resected specimen was negative for adenocarcinoma, however the horizontal stump was positive for adenoma. We administered steroid suppositories to prevent stenosis. After ESD, general fatigue and diarrhea disappeared and electrolyte disorders resolved. The patient had good clinical outcome without recurrence or stenosis.
Factitious Disorder in Crohn's Disease: Recurrent Pancytopenia Caused by Surreptitious Ingestion of 6-Mercaptopurine
Authors: Kahn Allon , Boroff Erika S. , Martin Kari A. , Northfelt Donald W. , Heigh Russell I.
Published: June 2015

Factitious disorder is a rare psychiatric illness characterized by the willful and deceptive induction of illness for the purpose of assuming the sick role. It presents a substantial diagnostic challenge, as patients often go to great lengths to conceal their deception. Accordingly, its presence in the full spectrum of gastrointestinal diseases is likely underappreciated. While factitious gastrointestinal bleeding, abdominal pain and diarrhea are relatively common, factitious non-gastrointestinal symptoms in the setting of gastrointestinal illness have been infrequently reported. We present the case of a patient with Crohn's disease with recurrent pancytopenia attributed to the surreptitious ingestion of 6-mercaptopurine. In patients with possible access to immunomodulatory drugs, a high suspicion for and early identification of factitious disorder may improve patient outcomes and avoid invasive and costly diagnostic evaluations.
X4 Tropic Virus Prediction Is Associated with a Nadir CD4 T-Cell Count below 100 Cells/mm3
Authors: Sechet Matthieu , Roussel Catherine , Schmit Jean-Luc , Saroufim Carlo , Ghomari Kamel , Merrien Dominique , Cordier François , Pik Jean-Jacques , Landgraf Nathalie , Douadi Youcef , Liné Dominique , Duverlie Gilles , Castelain Sandrine
Published: June 2015

Objective: The aim of this study was to evaluate tropism prediction performances of three algorithms [geno2pheno false-positive rate 10% (G2P10), position-specific scoring matrix (PSSM) and a combination of the 11/25 and net charge rules] and to investigate the viral and host factors potentially involved in the X4 or R5 prediction in human immunodeficiency virus-1 (HIV-1) patients. Methods: Viral tropism was determined in 179 HIV-1-infected patients eligible for CCR5 antagonist therapy. HIV-1 RNA or DNA was extracted and amplified for env gp120 sequencing. In parallel, demographic, viral, immunological and clinical determinants were analyzed. Results: According to the G2P10 algorithm, 48 patients harbored X4 or X4R5 virus. The tropism prediction was concordant for 87.7 and 88.2% of samples when comparing G2P10 with PSSM or with a combination of the 11/25 and net charge rules, respectively. X4 prediction was significantly associated with more than 35 amino acids in the V3 domain (p < 0.0001) and loss of an N-linked glycosylation site (p < 0.0001). Of the factors studied, only the nadir CD4 T-cell count was significantly associated with X4 tropism (p = 0.01). Conclusion: We determined that the X4 virus detection is closely linked to the nadir CD4 T-cell count below 100 cells/mm3 that must be taken into account when considering a CCR5 antagonist therapy switch.
Pulmonary Adenocarcinoma Metastatic to the Choroid Diagnosed by Biopsy of an Extrascleral Nodule
Authors: Jakobiec Frederick A. , Ramsey David J. , Stagner Anna M. , Wu David M. , Yoon Michael K.
Published: June 2015

Purpose/Background: To report a patient with orbital extension of a choroidal metastasis produced by a pulmonary adenocarcinoma which was diagnosed by biopsy of the extrascleral nodule. Methods: Clinical history and imaging studies (including fundus photography, autofluorescence, fluorescein angiography, B-scan, and orbital MRI) were reviewed along with histopathologic and immunohistochemical studies. Results: A 60-year-old woman presented with decreased vision in the right eye. Fundus examination revealed a leopard-spotted choroidal lesion and associated serous retinal detachment. Imaging disclosed an enhancing orbital lesion abutting the sclera near the choroidal mass, which had spread outside of the eye. Histopathology revealed lumen-forming cells elaborating mucin. The cells were immunohistochemically positive for epithelial membrane antigen, thyroid transcription factor 1, and cytokeratin 7 and negative for cytokeratin 20. This was consistent with a pulmonary adenocarcinoma. Widespread metastases were subsequently found. Conclusions: This is the first detailed case report of a successful biopsy of the orbital extension of an essentially posterior intraocular tumor. Such a maneuver permits a much more generous tissue sample than a needle biopsy. In the current case, a large tissue sample provided the basis for complete immunohistochemical evaluation, leading to the diagnosis of an intraocular metastatic mucin-producing adenocarcinoma of lung origin.
The Emerging Role of Inhibitor of Growth 4 as a Tumor Suppressor in Multiple Human Cancers
Authors: Cui Shiyun , Gao Yanping , Zhang Kai , Chen Jing , Wang Rui , Chen Longbang
Published: June 2015

Inhibitor of growth 4 (ING4), a member of the conserved ING family, has been identified as an important tumor suppressor since it plays a critical role in the regulation of chromatin modification, cell proliferation, angiogenesis and cell migration. Some observations suggest that ING4 acts as a key regulator of tumorigenesis through modifying gene transcription in part by regulating the transcription factors p53 and NF-kappaB (NF-κB). However, these models have yet to be substantiated by further investigations. Numerous reports describe the reduced expression of ING4 in cancers, and the responsible mechanisms are involved in gene deletion, mutation, transcriptional and post-transcriptional dysregulation. This review aims to summarize the recent published literature that investigates the role of ING4 in regulating tumorigenesis and progression, and explore its potential for cancer treatment.
Identify Potential Regulators in HIV-1 Latency by Joint microRNA and mRNA Analysis
Authors: Yang Zongxing , Yang Jin , Wang Juan , Lu Xiangyun , Jin Changzhong , Xie Tiansheng , Wu Nanping
Published: June 2015

Background/Aims: The main obstacle to cure HIV infection is the existence of long-lasting latent reservoirs. Many efforts have been made to understand basal mechanisms of HIV-1 latency, in which miRNAs play an important role. However, integrated analysis of miRNA and mRNA expression in HIV-1 latency is lacking. Methods and Results: Global miRNA and mRNA expression was determined by microarrays and quantitative reverse transcription PCR in well-characterized HIV-1 latently and actively infected cells, respectively. Interactions of miRNA-mRNA, mRNA-mRNA, and transcription factor-miRNA pairs were assembled into the function network. Our results show that transcription regulation related genes were mostly enriched in HIV-1 latently infected cells. Gene set enrichment analysis revealed nuclear transport related pathways were up-regulated in the latency group. Network dynamic analysis highlighted many gene-pairs sharing the largest changes in different HIV-1 infection state. 83.33% miRNA-target pairs were validated against database, and RHOB related genes constitute the interface between HIV-1 latency and replication state. Conclusion: We show for the first time a joint miRNA and mRNA expression profile related to a HIV-1 latency phenotype, outline a dynamic network of potential regulators involving in HIV-1 latency or replication state, and gain new insights into the source messages for affecting HIV-1 latency.
IFN Regulatory Factor-1 Modulates the Function of Dendritic Cells in Patients with Acute Coronary Syndrome
Authors: Guo Min , Yan Rui , Wang Caixia , Shi Hongtao , Sun Meng , Guo Shuang , Xiao Chuanshi
Published: June 2015

Background: Atherosclerosis is widely recognized as a complex inflammatory disease involving pathogenic immune response of T cells and antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. Accumulating evidence has revealed that mature DCs play critical roles in the differentiation of effector T cells into CD4+ T cells, which effectively participate in the onset of acute coronary syndrome (ACS). IFN regulatory factor (IRF)-1 has been shown to be involved in various immune processes. The role of IRF-1 in DCs in the pathogenesis of ACS has not been investigated. Methods and Results: We examined the relative mRNA and protein expression of IRF-1 in human monocyte-derived DCs in patients with coronary artery disease (CAD). The overexpression or silencing of IRF-1 expression in DCs in patients with ACS was performed to explore the possible role of IRF-1 in the maturation and function of DCs involved in ACS. The results showed that the relative expression of IRF-1 in DCs is obviously increased in patients with ACS. The overexpression or silencing of IRF-1 expression could effectively promote or attenuate the maturation and function of DCs. In addition, we revealed that the MAPK pathway (phosphorylation of JNK, p38 and ERK1/2) might be downstream of IRF-1 signalling pathway in activation of circulating DCs in ACS patients. Conclusion: The present data demonstrate that IRF-1 could effectively promote the immune maturation and function of DCs in ACS patients.
MicroRNA-130a Targets MAP3K12 to Modulate Diabetic Endothelial Progenitor Cell Function
Authors: Ye Meng , Li Dan , Yang Jian , Xie Jing , Yu Fei , Ma Yushui , Zhu Xuchao , Zhao Jinwei , Lv Zhongwei
Published: June 2015

Aims: The aim of the present study was to explore the influence of microRNA (miR)-130a dysregulation on the JNK signal pathway through its target MAP3K12 in diabetic endothelial progenitor cells (EPCs). Methods: The expression of miR-130a was compared between diabetic and normal EPCs. Computational target prediction was performed to identify MAP3K12 as a functionally relevant target of miR-130a in EPCs. The role of miR-130a was investigated regarding its anti-apoptotic effects and its role on the regulation of EPC function was evaluated through the negative regulation of the JNK signal pathway Results: MiR-130a expression was significantly downregulated in diabetic EPCs, and cell proliferation was reduced in EPCs under high glucose condition. miR-130a inhibited the JNK pathway by targeting MAP3K12, contributing to its anti-apoptotic effect and the maintenance of EPC function. In diabetic EPCs, high glucose affects the expression of miR-130a, inducing sustained JNK activation and promoting EPC apoptosis and dysfunction. Conclusions: Downregulation of miR-130a may underlie endothelial dysfunction in diabetes through the activation of JNK signal pathway.
Periostin Mediates TGF-β-Induced Epithelial Mesenchymal Transition in Prostate Cancer Cells
Authors: Hu Qingfeng , Tong Shijun , Zhao Xiaojun , Ding Weihong , Gou Yuancheng , Xu Ke , Sun Chuanyu , Xia Guowei
Published: June 2015

Background: In our previous study, we found that periostin was upregulated in prostate cancer, and its expression could be modulated by TGF-β. TGF-β could upregulate periostin expression in some cells, and both TGF-β and periostin could induce epithelial mesenchymal transition (EMT). We aimed to study the effect of periostin in the process of TGF-β-induced EMT in prostate cancer cells. Methods: We constructed a lentivirus vector containing the periostin gene and transduced it into PC3 and DU145 cells. After confirming periostin overexpression by PCR and Western blotting, we used an MTT assay to establish a growth curve to measure cell proliferation. Additionally, we performed transwell and wound healing assays to measure cell invasion and migration, respectively. Lastly, we measured the expression of EMT associated factors using Western blot analysis to test the effect of periostin on EMT in prostate cancer cells. Results: PCR and Western blot analyses confirmed that periostin was upregulated after infection with the periostin lentiviral vector. Periostin overexpression promoted increased cell proliferation, invasion, and migration as measured by MTT, transwell, and wound healing assays, respectively. Western blot analysis illustrated that periostin overexpression increased the expression of EMT associated factors, and periostin overexpression activated Akt and GSK-3β, which could be inhibited using a PI3K inhibitor. Additionally, TGF-β increased the levels of STAT3, Twist1 and periostin, while both STAT3 shRNA and Twist1 shRNA inhibited periostin expression. However, STAT3 shRNA also decreased Twist1 expression. Although reduction of STAT3, Twist1 or periostin levels with shRNA inhibited TGF-β-induced overexpression of EMT associated factors, periostin overexpression could reverse such inhibition by interfering with STAT3 and Twist1. Similarly, periostin overexpression also reversed inhibition of cell invasion induced by interference of STAT3 and Twist1. Conclusion: Our findings indicate that periostin is an important mediator of TGF-β-induced EMT and suggest that periostin is a potential therapeutic target for suppressing the metastatic progression of prostate cancer.
Identification and Characterization of a Novel IL-4 Receptor α Chain (IL-4Rα) Antagonist to Inhibit IL-4 Signalling
Authors: Ahmed Nayyar , Dhanapala Pathum , Suphioglu Cenk
Published: June 2015

Background/Aims: In recent times, allergy has become a financial, physical and psychological burden to the society as a whole. In allergic cascades, cytokine IL-4 binds to IL-4 receptor (IL-4R), consequently producing allergen-specific IgE antibodies by B cells. In addition, among other functions, IL-4 is also responsible for B and T cell proliferation and differentiation. Hence, characterization of novel antagonists that inhibit IL-4 signalling forms the overall aim of this study. Methods: Phage display was used to screen a random 12-mer synthetic peptide library with a human IL-4Rα to identify peptide candidates. Once identified, the peptides were commercially synthesized and used for in vitro immunoassays. Results: We have successfully used phage display to identify M13 phage clones that demonstrated specific binding to IL-4Rα. The peptide N1 was synthesized for use in ELISA, demonstrating significant binding to IL-4Rα and inhibiting interaction with cytokine IL-4. Furthermore, the peptide was tested in a transfected HEK-Blue IL-4 reporter cell line model, which produces alkaline phosphatase (AP). QUANTI-Blue, a substrate, breaks down in the presence of AP producing a blue coloration. Using this colorimetric analysis, >50% inhibition of IL-4 signalling was achieved. Conclusion: We have successfully identified and characterised a synthetic peptide antagonist against IL-4Rα, which effectively inhibits IL-4 interaction with the IL-4Rα in vitro. Since IL-4 interaction with IL-4Rα is a common pathway for many allergies, a prophylactic treatment can be devised by inhibiting this interaction for future treatment of allergies.
Ginsenoside Rh2 Suppresses Neovascularization in Xenograft Psoriasis Model
Authors: Zhou Jing , Gao Yunlu , Yi Xuemei , Ding Yangfeng
Published: June 2015

Background/Aims: Psoriasis is a common inflammatory skin disease of undetermined etiology and poor prognosis. The current therapies have focused on direct inhibition of local inflammation, e.g. through hormone treatments. However, neovascularization plays a critical role in the development of psoriasis but so far no therapies have been developed to suppress psoriasis-associated neovascularization. Methods: We treated AGR129 mice that had received human PN skin grafts with different doses of Ginsenoside Rh2 (GRh2). The acanthosis and papillomatosis index were evaluated. The percentage of T lymphocytes in the grafts was quantified by flow cytometry. The levels of vascularization in the grafts were quantified based on CD31-positive area. We examined the levels of VEGF-A in the skin treated with GRh2. We treated AGR129 mice that had received human PN skin grafts with different doses of soluble Flt-1 (sFlt1) and then evaluated the effects on the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density. Results: GRh2 dose-dependently decreased the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density in PN skin grafts in mice. GRh2 inhibited VEGF-A levels in the PN skin grafts. Treatment with sFlt1 mimicked the effects of GRh2 on the acanthosis and papillomatosis index, T lymphocyte percentage and vessel density in PN skin grafts in mice. Conclusions: GRh2 may have an anti-psoriasis effect through neovascularization suppression.
The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach
Authors: Karimian Hamed , Fadaeinasab Mehran , Moghadamtousi Soheil Zorofchian , Hajrezaei Maryam , Zahedifard Maryam , Razavi Mahboubeh , Safi Sher Zaman , Mohan Syam , Khalifa Shaden A.M. , El-Seedi Hesham R. , Abdulla Mahmood Amin , Ali Hapipah Mohd , Noordin Mohamad Ibrahim
Published: June 2015

Background: Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models. Methods and Results: Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels. Conclusion: This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.
Clinico-Pathological Correlations of the Frontal Lobe Syndrome: Results of a Large Brain Bank Study
Authors: Krudop Welmoed A. , Bosman Sjanne , Geurts Jeroen J.G. , Sikkes Sietske A.M. , Verwey Nicolaas A. , Stek Max L. , Scheltens Philip , Rozemuller Annemieke J.M. , Pijnenburg Yolande A.L. ,   Netherlands Brain Bank
Published: June 2015

Aims: A clinical frontal lobe syndrome (FLS) is generally attributed to functional or structural disturbances within frontal-subcortical circuits. We studied the distribution of pathological brain changes in FLS. Additionally, the prevalence of FLS among various disorders was studied. Methods: We systematically screened clinical files of donors to the Netherlands Brain Bank (n = 2,814) for FLS. A total of 262 FLS cases were identified, and the distribution of postmortem pathological changes within the frontal-subcortical circuits was extracted from their neuropathological reports. Results: In 244 out of 262 patients (93%), pathological changes within the frontal-subcortical circuits were found: 90 subjects (34%) with frontal cortical pathology and 18 (7%) with pathology restricted to subcortical grey matter nuclei, whereas 136 subjects (52%) showed both cortical and subcortical pathology. In 18 subjects (7%), no pathology was found in the examined areas. The prevalence of FLS was highest in frontal-temporal lobar degeneration, followed by progressive supranuclear palsy and vascular dementia [χ2(6, n = 1,561) = 222.64, p < 0.01]. Conclusion: In this large brain bank study, the distribution of pathological changes in subjects with FLS was shown to be frontal-subcortical for the first time. A minority of FLS cases had pathology in the subcortical regions only or no frontal pathology at all.
Long-Term Follow-Up of Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infection in a Dual Solid Organ Transplant Recipient
Authors: Bilal Mohammad , Khehra Raman , Strahotin Cristina , Mitre Ricardo
Published: June 2015

Clostridium difficile infection is one of the most frequent causes of healthcare-associated infections, and its rates are also increasing in the community. Mounting evidence suggests that fecal microbiota transplantation (FMT) may be effective; however, as there is paucity of data regarding the use of FMT in patients with solid organ transplants, we present a case of successful FMT in a patient with dual solid organ transplant.
Brachial-Ankle Pulse Wave Velocity: Myths, Misconceptions, and Realities
Authors: Sugawara Jun , Tanaka Hirofumi
Published: June 2015

A variety of techniques to evaluate central arterial stiffness have been developed and introduced. None of these techniques, however, have been implemented widely in regular clinical settings, except for brachial-ankle pulse wave velocity (baPWV). The most prominent procedural advantage of baPWV is its ease of use, since it only requires the wrapping of blood pressure cuffs on the 4 extremities. There is mounting evidence indicating the ability of baPWV to predict the risk of future cardiovascular events and total mortality. Additionally, the guidelines for the management of hypertension in Japan recommended the measurement of baPWV be included in the assessment of subclinical target organ damage. However, baPWV has not been fully accepted worldwide due to perceived theoretical and methodological issues. In this review, we address the most frequently mentioned questions and concerns regarding baPWV to shed some light on this simple and easy arterial stiffness measurement.
Qualität in der Weiterbildung: Aktueller Stand und Zukunft psychotherapeutischer Aus- und Weiterbildung
Authors: Tripp Jürgen , Schweiger Ulrich , Ströhm Walter , Stromberg Claudia , Quaschner Kurt
Published: June 2015

Das Reformkonzept der psychotherapeutischen Direktausbildung, das eine Angleichung der Ausbildungsstruktur der Psychologischen Psychotherapeuten und Kinder- und Jugendlichenpsychotherapeuten an die anderer akademischer Heilberufe mit einem durch eine Approbationsordnung geregelten Studium, Staatsexamen und anschließender Weiterbildung beinhaltet, stößt zum Teil auf deutliche Kritik. Insbesondere wird kritisiert, dass in einer Weiterbildung analog zur Facharztausbildung die Qualität der jetzigen Psychotherapieausbildung nicht aufrechterhalten werden könne. Um diese Diskussion auf eine fundierte Basis zu stellen, legen wir dar, was aus unserer Sicht zur Qualität psychotherapeutischer Ausbildung beiträgt, und stellen empirische Befunde zur Qualität der Psychotherapieausbildung sowie zur ärztlichen Weiterbildung vor. Dargestellt werden außerdem Konsequenzen für eine zukünftige Weiterbildung nach einer Direktausbildung, welche notwendig erscheinen, um für eine hohe Qualität des Kompetenzerwerbs zu sorgen: Die Weiterbildung sollte eine Verbindung von praktischem Erfahrungserwerb unter Anleitung mit den bewährten bisherigen Ausbildungselementen wie Theorieworkshops und Selbsterfahrung ermöglichen. Es sollten verschiedene Versorgungssettings und Patientengruppen kennengelernt werden. Die bisherigen Ausbildungsinstitute sollten als Weiterbildungsinstitute weiterhin eine zentrale Rolle spielen und mit anderen Weiterbildungsstätten kooperieren. Der Kompetenzerwerb sollte beschrieben werden und überprüfbar sein und den Psychotherapeutenkammern käme eine wichtige Funktion als Aufsichts- und Anerkennungsinstanz zu. Damit diese Qualitätsmerkmale umgesetzt werden können, müssen die Weiterbildungsstrukturen finanziell ausreichend ausgestattet werden.
The Q* Index: A Useful Global Measure of Dementia Screening Test Accuracy
Authors: Larner A.J.
Published: June 2015

Background/Aims: Single, global or unitary, indicators of test diagnostic performance have intuitive appeal for clinicians. The Q* index, the point in receiver operating characteristic (ROC) curve space closest to the ideal top left-hand corner and where test sensitivity and specificity are equal, is one such measure. Methods: Datasets from four pragmatic accuracy studies which examined the Mini-Mental State Examination, Addenbrooke's Cognitive Examination-Revised, Montreal Cognitive Assessment, Test Your Memory test, and Mini-Addenbrooke's Cognitive Examination were examined to calculate and compare the Q* index, the maximal correct classification accuracy, and the maximal Youden index, as well as the sensitivity and specificity at these cutoffs. Results: Tests ranked similarly for the Q* index and the area under the ROC curve (AUC ROC). The Q* index cutoff was more sensitive (and less specific) than the maximal correct classification accuracy cutoff, and less sensitive (and more specific) than the maximal Youden index cutoff. Conclusion: The Q* index may be a useful global parameter summarising the test accuracy of cognitive screening instruments, facilitating comparison between tests, and defining a possible test cutoff value. As the point of equal sensitivity and specificity, its use may be more intuitive and appealing for clinicians than AUC ROC.
Recurrent Facial Erythema with Cytotoxic T Cell Infiltration as a Possible Reactive Eruption in a Human T-Cell Lymphotropic Virus Type 1 Carrier
Authors: Kaneko Yasuhiro , Tatsuno Kazuki , Fujiyama Toshiharu , Ito Taisuke , Tokura Yoshiki
Published: June 2015

Human T-cell lymphotropic virus type 1 (HTLV-1) induces adult T cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. Approximately half of ATLL patients have direct skin involvement of neoplastic cells. However, there exist HTLV-1-associated reactive eruptions with a predominant infiltrate of non-neoplastic CD8+ T cells in ATLL, HAM/TSP and carrier. A 50-year-old Japanese female HTLV-1 carrier had several episodes of itchy, indurated erythema that occurred diffusely on the face and neck, lasted for 2 weeks and spontaneously subsided without sequelae. Histopathologically, CD3+ T cells infiltrated the upper dermis, and part of the infiltrating cells were CD4+CD25+, sharing the phenotype with ATLL neoplastic cells. An aggregate of CD8+ T cells bearing the cytotoxic molecule TIA-1 was also present. It is possible that skin-affinitive HTLV-1+CD4+ T cells propagated and subsequently disappeared as a result of cytotoxic T cell attack.
Short- and Long-Term Stroke Risk after Urgent Management of Transient Ischaemic Attack: The Bologna TIA Clinical Pathway
Authors: Guarino Maria , Rondelli Francesca , Favaretto Elisabetta , Stracciari Andrea , Filippini Massimo , Rinaldi Rita , Zele Ivana , Sartori Michelangelo , Faggioli Gianluca , Mondini Susanna , Donti Andrea , Strocchi Enrico , Degli Esposti Daniela , Muscari Antonio , Veronesi Maddalena , D''Addato Sergio , Spinardi Luca , Faccioli Luca , Pastore Trossello Marco , Cirignotta Fabio
Published: June 2015

Background: Rapid management can reduce the short stroke risk after transient ischaemic attack (TIA), but the long-term effect is still little known. We evaluated 3-year vascular outcomes in patients with TIA after urgent care. Methods: We prospectively enrolled all consecutive patients with TIA diagnosed by a vascular neurologist and referred to our emergency department (ED). Expedited assessment and best secondary prevention was within 24 h. Endpoints were stroke within 90 days, and stroke, myocardial infarction, and vascular death at 12, 24 and 36 months. Results: Between August 2010 and July 2013, we evaluated 686 patients with suspected TIA; 433 (63%) patients had confirmed TIA. Stroke at 90 days was 2.07% (95% confidence interval (CI), 1.1-3.9) compared with the ABCD2-predicted risk of 9.1%. The long-term stroke risk was 2.6% (95% CI, 1.1-4.2), 3.7% (95% CI, 1.6-5.9) and 4.4% (95% CI, 1.9-6.8) at 12, 24 and 36 months, respectively. The composite outcome of stroke, myocardial infarction, and vascular death was 3.5% (95% CI, 1.7-5.1), 4.9% (95% CI, 2.5-7.4), and 5.6% (95% CI, 2.8-8.3) at 12, 24, and 36 months, respectively. Conclusions: TIA expedited management driven by vascular neurologists was associated with a marked reduction in the expected early stroke risk and low long-term risk of stroke and other vascular events.
Downregulation of BDNF Expression by PKC and by TNF-α in Human Endothelial Cells
Authors: Xu Hui , Czerwinski Petra , Xia Ning , Förstermann Ulrich , Li Huige
Published: June 2015

Brain-derived neurotrophic factor (BDNF) is a neurotrophin best characterized for its survival and differentiative effects on neurons. Recent studies demonstrated that BDNF and its receptors are also expressed in the peripheral vasculature, where it stimulates angiogenesis and promotes the survival of endothelial cells. This study was designed to investigate the angiogenic effects of BDNF and its expressional regulation by tumor necrosis factor (TNF-α) and protein kinase C (PKC) in endothelial cells. In the Matrigel angiogenesis assay, BDNF-stimulated vascular tube formation of human umbilical vein endothelial cells (HUVEC) was completely blocked by an inhibition of the TrkB receptor, but only partially inhibited by the inhibition of the p75NTR signaling. Treatment of HUVEC and HUVEC-derived EA.hy 926 cells with TNF-α resulted in a downregulation of BDNF expression, which could be prevented by the TNFR1 antagonist WP9QY. BDNF downregulation by TNF-α was associated with decreased angiogenic activity of HUVEC. The effect of TNF-α on BDNF expression could not be abolished by the inhibition of PKC. Treatment of HUVEC and EA.hy 926 cells with PKC-activating phorbol esters (phorbol-12-myristate-13-acetate, PMA or phorbol-12,13-dibutyrate) resulted in a downregulation of BDNF expression, whereas the inactive 4α-phorbol-12,13-didecanoate was without effect. PMA had no significant effect on BDNF mRNA stability and the downregulation of BDNF mRNA expression by PKC activation was likely a transcriptional event. BDNF downregulation by PMA could be prevented by PKC inhibitors Gö 6983 and rottlerin, but not by Gö 6976. Thus, a Gö 6983/rottlerin-sensitive PKC isoform is likely to be responsible for PMA-induced BDNF downregulation.
Protein Profiling of Women with Spontaneous Preterm Birth
Authors: Immaculate Mbongo Langmia , Yamunah Devi Apalasamy , Zain Shamsul , Omar Siti Zawiah , Mohamed Zahurin
Published: June 2015

Background: Preterm birth (PTB) is the largest cause of neonatal mortality and morbidity in the world. Ethnicity disparity in the occurrence of PTB has been associated with the cytokine function. In this study, we aimed at examining cytokine levels in women with spontaneous preterm and term births. Method: Women with spontaneous preterm birth (SPTB) between 24 and 31 weeks (n = 40) and women with spontaneous term birth between 37 and 41 weeks (n = 40) admitted to the University of Malaya Medical Centre from 2011 to 2013 were involved in this study. Plasma proteins were determined for 35 cytokines using ProcartaPlex™ immunoassay. Protein levels were compared between women with SPTB and women with term birth. Result: Six specific cytokines were significantly high among women with SPTB. This includes TNFA (odds ratio (OR) 3.4, 95% confidence interval (CI) 2.0-6.0, p = 0.001), MCP-3 (OR 2.5, 95% CI 1.29-4.67, p = 0.007), IL16 (OR 2.4, 95% CI 1.34-4.30, p = 0.003), IL17A (OR 2.3, 95% CI 1.28-4.06, p = 0.005), IFNG (OR 3.8, 95% CI 2.0-8.0, p = 0.001), and farctalkine (OR 2.1, 95% CI 1.17-4.22, p = 0.031), respectively. Conclusion: This study identifies high levels of specific cytokines in women with PTB. These inflammatory biomarkers may play an important role in the mechanisms that result in uterine contraction and PTB.
Fibroblast Growth Factor-23 and Vitamin D Metabolism in Subjects with eGFR ≥60 ml/min/1.73 m2
Authors: Nakatani Shinya , Nakatani Ayumi , Tsugawa Naoko , Yamada Shinsuke , Mori Katsuhito , Imanishi Yasuo , Ishimura Eiji , Okano Toshio , Inaba Masaaki
Published: June 2015

Background/Aims: Fibroblast growth factor (FGF)-23 and parathyroid hormone (PTH) are both potent phosphaturic hormones. Since they exert opposite effects on vitamin D metabolism, the measurement of 3 vitamin D metabolites; 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D), allows the distinction of the effects of FGF-23 from those of PTH. The aim of this study was to elucidate which factor, FGF-23 or PTH, plays a more important role in the regulation of vitamin D metabolites in subjects with estimated glomerular filtration (eGFR) ≥60 ml/min/1.73 m2. Methods: Subjects with eGFR ≥60 ml/min/1.73 m2 (n = 20) were enrolled and their serum levels of FGF-23, intact PTH, and vitamin D metabolites were determined. Results: Serum FGF-23 correlated inversely with 1,25(OH)2D (r = -0.717, p = 0.0004) and the 1,25(OH)2D/25-OH-D ratio (r = -0.518, p = 0.019), compared with a significant positive correlation between serum intact PTH and the 1,25(OH)2D/25-OH-D ratio (r = 0.562, p = 0.010). Multiple regression analyses revealed serum FGF-23 as a significant factor that was associated with serum 1,25(OH)2D (β = -0.593, p = 0.018), 1,25(OH)2D/25-OH-D ratio (β = -0.521, p = 0.025), and the 24,25(OH)2D/1,25(OH)2D ratio (β = 0.632, p = 0.008), and intact PTH as a significant factor associated with the 1,25(OH)2D/25-OH-D ratio (β = 0.445, p = 0.028). Conclusions: This study demonstrated that, even in subjects with eGFR ≥60 ml/min/1.73 m2, FGF-23 might play an important role in the regulation of vitamin D metabolism. In addition to the established role of PTH, the association between FGF-23 and indices of vitamin D metabolism suggested the potential role of FGF-23 on phosphate metabolism in such patients.
Increased Ocular Pulse Amplitude Associated with Unilateral Dysgenesis of the Orbital Roof
Authors: Vira Ami Shah , Mahmoud Ashraf M. , Roberts Cynthia J. , Katz Steven E.
Published: June 2015

Introduction: Two patients (one with neurofibromatosis type 1) presented with unilateral ocular pulsation. Methods: A CT scan of the orbits revealed extensive dysgenesis of the orbital roof with herniation of the frontal lobe into the orbit in both cases. PASCAL dynamic contour tonometry was performed. Results: The ipsilateral ocular pulse amplitude (OPA) was greater than the contralateral side, and the ocular pulse waveform morphology more closely approximated the known intracranial waveform in these patients. Conclusions: We hypothesize that the greater OPA was due to stronger transmission of the intracranial pressure waveform amplitude and morphology in the absence of the orbital roof.
Iatrogenic Colonic Perforation due to Computed Tomographic Colonography
Authors: Kato Takashi , Muroya Tsukasa , Goda Takayuki , Takabayashi Ken , Sasaki Kiyotaka , Takahashi Toshiyuki , Horita Shoichi
Published: June 2015

Although the complications of computed tomographic colonography (CTC) are very rare, CTC is associated with potential risk of colonic perforation. In the present report we describe two cases of colonic perforation secondary to CTC. In the first case with ascending colonic carcinoma, insertion of a rigid double-balloon catheter caused direct rectal wall perforation. In the second case with obstructive colonic carcinoma, pneumoperitoneum developed due to automated carbon dioxide insufflation. Both patients were asymptomatic after examination and recovered without any complications. Based on the findings of the current cases, we recommend that a soft-tip catheter be used for CTC, and suggest that colonic perforation can occur even with automatic insufflation, depending on patient characteristics.
Incidence of Newborn Stabilization and Resuscitation Measures and Guideline Compliance during the First Minutes of Life in Norway
Authors: Skåre Christiane , Kramer-Johansen Jo , Steen Thorbjørn , Ødegaard Silje , Niles Dana E. , Nakstad Britt , Solevåg Anne L. , Nadkarni Vinay M. , Olasveengen Theresa M.
Published: June 2015

Background: Most newborns manage the transition from intra- to extrauterine life without interventions, yet neonatal morbidity caused by failure of transition remains an important health problem. Objective: To determine the incidence of neonatal stabilization and resuscitation measures and guideline compliance during the first minutes after birth. Methods: This is a prospective, observational study of all births in three Norwegian hospitals. All interventions performed, including suctioning, use of pulse oximetry, continuous positive airway pressure (CPAP), positive pressure ventilation (PPV), supplemental oxygen, intubation, and administration of drugs, were registered at every on-call team shift during the study period. Results: A total of 1,507 live-born infants were included, of whom 264 (18%) were brought to the resuscitation crib. Oropharyngeal suctioning was performed in 77 (5%), deep blind suctioning was carried out in 10 (1%) and 84 (6%) were monitored using pulse oximetry. PPV was provided in 58 cases (4%) - 8 (21%) of <34 weeks and 50 (3%) of ≥34 weeks of gestation. Sustained inflation is not routinely used in these departments. CPAP (without PPV) was provided in 17 cases (1%) - 4 (0.3%) were intubated and ventilated through the endotracheal tube. Supplemental oxygen was given to 39 infants (3%) - 9 without pulse oximetry monitoring. The median (interquartile range) birth weight and gestational age of the newborns requiring PPV and/or CPAP were 3,220 g (2,643-3,858) and 39 weeks (37-41), respectively. Conclusion: In this study, the need for resuscitation and/or stabilization measures was commonly considered, and 4% of all newborns received PPV. Despite strong guideline emphasis on the use of pulse oximetry to guide oxygen administration, many infants received oxygen treatment without pulse oximetry monitoring.
Carotid Artery Stenting Successfully Prevents Progressive Stroke Due to Mobile Plaque
Authors: Oomura Masahiro , Sato Chikako , Yamada Kentaro , Ikeda Toshimasa , Anan Chise , Kamimoto Kaoru
Published: June 2015

We report a case of progressive ischemic stroke due to a mobile plaque, in which carotid artery stenting successfully prevented further infarctions. A 78-year-old man developed acute multiple infarcts in the right hemisphere, and a duplex ultrasound showed a mobile plaque involving the bifurcation of the left common carotid artery. Maximal medical therapy failed to prevent further infarcts, and the number of infarcts increased with his neurological deterioration. Our present case suggests that the deployment of a closed-cell stent is effective to prevent the progression of the ischemic stroke due to the mobile plaque.
Plasma Catecholamine Profile of Subarachnoid Hemorrhage Patients with Neurogenic Cardiomyopathy
Authors: Moussouttas Michael , Mearns Elizabeth , Walters Arthur , DeCaro Matthew
Published: June 2015

Purpose: To investigate the connection between sympathetic function and neurogenic cardiomyopathy (NC), and to determine whether NC is mediated primarily by circulating adrenal epinephrine (EPI) or neuronally transmitted norepinephrine (NE), following subarachnoid hemorrhage (SAH). Methods: This is a prospective observational investigation of consecutive severe-grade SAH patients. All participants had transthoracic echocardiography and serological assays for catecholamine levels - dopamine (DA), NE and EPI - within 48 h of hemorrhage onset. Clinical and serological independent predictors of NC were determined using multivariate logistic regression analyses, and the accuracy of predictors was assessed by receiver operating characteristic (ROC) curves. Multivariate linear regression analyses were used to evaluate correlations among the catecholamines. Results: The investigation included a total of 94 subjects: the mean age was 55 years, 81% were female and 57% were Caucasian. NC was identified in approximately 10% (9/94) of cases. Univariate analyses revealed associations between NC and worse clinical severity (p = 0.019), plasma DA (p = 0.018) and NE levels (p = 0.024). Plasma NE correlated with DA levels (ρ = 0.206, p = 0.046) and EPI levels (ρ = 0.392, p < 0.001), but was predicted only by plasma EPI in bivariate [parameter estimate (PE) = 1.95, p < 0.001] and multivariate (PE = 1.89, p < 0.001) linear regression models. Multivariate logistic regression analyses consistently demonstrated the predictive value of clinical grade for NC (p < 0.05 for all analyses) except in models incorporating plasma NE, where NC was independently predicted by NE level (OR 1.25, 95% CI 1.01-1.55) over clinical grade (OR 4.19, 95% CI 0.874-20.1). ROC curves similarly revealed the greater accuracy of plasma NE [area under the curve (AUC) 0.727, 95% CI 0.56-0.90, p = 0.02] over clinical grade (AUC 0.704, 95% CI 0.55-0.86, p = 0.05) for identifying the presence or absence of NC. Conclusions: Following SAH, the development of NC is primarily related to elevated plasma NE levels. Findings implicate a predominantly neurogenic process mediated by neuronal NE (and not adrenal EPI), but cannot exclude synergy between the catecholamines.