bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Parathyroid Hormone Affect Erythropoietin Therapy in Dialysis Patients?
Authors: Al-Hilali Nabieh , Al-Humoud Hani , Ninan Vadakethu T. , Nampoory Mangalathillam R.N. , Puliyclil Mini A. , Johny Kaivilayil V.
Published: December 2006

Objective: The objective of this study was to assess the response to recombinant human erythropoietin (rHuEPO) during treatment of anemia in dialysis patients with hyperparathyroidism. Subjects and Methods: A total of 118 patients with stage 5 renal failure on dialysis therapy were selected for this study. Anemia was treated with rHuEPO. Laboratory data for each patient included intact parathyroid hormone (iPTH), hemoglobin (Hb), hematocrit (Hct), blood urea nitrogen, serum creatinine, calcium, phosphate, and alkaline phosphatase. Patients with iPTH >32 pmol/l were considered hyperparathyroid. Erythropoietin resistance index (ERI) was expressed as the ratio of weekly rHuEPO dose/Hct level. Results: Of the 118 patients, 83 (70.3%) were on hemodialysis (HD) and 35 (29.7%) were on continuous ambulatory peritoneal dialysis (CAPD). Sixty-three patients (64.3%) with iPTH >32 pmol/l had Hb <11 g/dl, while 34 (54.8%) with iPTH <32 had Hb >11 g/dl (p = 04). Thirty-three (56%) patients with iPTH >32 pmol/l had hemocrit <33%, while 38 (61.3%) with iPTH <32 had hemocrit <33% (p = 0.4). The median value of weekly rHuEPO dose in HD patients (12,000 units) was significantly higher in comparison with CAPD patients (6,000 units; p < 0.0001). ERI was significantly higher in HD than CAPD patients with iPTH <16 pmol/l (p = 0002) as well as with patients with 16–32 pmol/l (p = 0.012). Conclusions: CAPD patients showed a reduced requirement for rHuEPO and better control of anemia compared with HD patients. ERI was also lower in CAPD than in HD patients. Hyperparathyroidism is a parameter predictive of rHuEPO hyporesponsiveness in dialysis patients.
Hydatid Disease of the First Rib Causing Thoracic Outlet Syndrome
Authors: Gezer Suat , Altınok Tamer , Ağaçkıran Yetkin , Taştepe İrfan
Published: December 2006

Objective: To present a case of hydatid disease of the first rib as a rare cause of thoracic outlet syndrome. Clinical Presentation: A 57-year-old female patient who had suffered from pain on the left shoulder radiating to the arm and numbness and weakness on the left arm for 3 months was admitted to our hospital. She had undergone an operation due to a mass lesion of the first rib compressing the thoracic outlet which was detected in the preoperative examinations. During the intraoperative examination it was decided that the lesion was a hydatid cyst and the first rib was totally resected. Conclusion: This report shows that hydatid disease should be taken into consideration amongst the tumoral diseases of the first rib as a very rare cause of thoracic outlet syndrome.
Expression of Tyrosine Kinase Receptors in Malignant Midgut Carcinoid Tumors
Authors: Welin Staffan , Fjällskog Marie Louise , Saras Jan , Eriksson Barbro , Janson Eva T.
Published: December 2006

Background: The expression of certain tyrosine kinase receptors (TKR) has been shown to have a prognostic value in many tumor entities. In recent years, inhibitors and monoclonal antibodies directed towards these receptors have been developed. Several have shown antitumoral effects and have been tested in clinical trials. We wanted to investigate whether midgut carcinoid tumors express TKR and therefore would be suitable for clinical trials with TKR inhibitors (TKRI) or monoclonal antibodies. Material and Methods: Tumor tissue from 36 patients (24 women and 12 men) with a malignant midgut carcinoid tumor was obtained. The tissues were examined with immunohistochemistry, using polyclonal antibodies against platelet-derived growth factor receptor-α (PDGFRα), platelet-derived growth factor receptor-β (PDGFRβ), epidermal growth factor receptor (EGFR) and c-kit. Human BON1 cells were cultivated and stimulated with PDGF-BB. We also present a case report of a patient with a malignant midgut carcinoid tumor who had stabilization of tumor growth during treatment with imatinib. Results: Immunohistochemical staining for PDGFRα in tumor cells showed immunoreaction for the receptor in 13/34 (38%) for PDGFRβ in 29/33 (88%), and 24/33 (73%) were immunoreactive for EGFR. No tumor tissue showed immunoreaction for c-kit. In tumor stroma PDGFRα was expressed in 35%, PDGFRβ in 94% and EGFR in 9%. We show that human neuroendocrine tumor cells respond to PDGF, indicating that these tumors express functional PDGF receptors. Conclusion: Malignant midgut carcinoid tumors may express three of the four TKR tested in this investigation. Therefore, these tumors might be susceptible for treatment with TKRI or monoclonal antibodies and this should be further explored in clinical trials.
Difference of Hepatitis B Virus Genotype Distribution in Two Groups of Mexican Patients with Different Risk Factors
Authors: Sánchez L.V. , Tanaka Y. , Maldonado M. , Mizokami M. , Panduro A.
Published: December 2006

Background: Hepatitis B virus (HBV) has been classified in eight genotypes, from A to H (HBV/A to HBV/H). HBV genotypes were determined in two groups with different risk factors. Methods: Group I consisted of 42 patients with chronic and acute hepatitis and group II with 25 men who have sex with men (MSM). HBV genotypes were determined by DNA sequencing of the S-gene. Results: Both groups differed with respect to genotype distribution (p < 0.001). In group I, there were 31 (74%), 9 (21%) and 2 patients (5%) with HBV/H, HBV/D and HBV/A; respectively. In group II, HBV/H, HBV/A, and HBV/G were found in 13 (52%), 8 (32%) and 4 (16%) cases, respectively. By using an HBV/G-specific PCR, 3 more cases of HBV/G were identified in group II, rising to a total 28%. All HBV/G strains were present in coinfection with other HBV genotypes, 86% with HBV/H, and 14% with HBV/A. Conclusions: HBV/H predominated in both groups. A high frequency of HBV/G was found in MSM, which was always coinfected with HBV/H or HBV/A. Significant differences in HBV genotype distribution were also found, since HBV/D was present only in patients with liver disease, whereas HBV/G was present only in MSM.
Long-Term Outcome after Interferon Therapy in Elderly Patients with Chronic Hepatitis C
Authors: Arase Yasuji , Ikeda Kenji , Suzuki Fumitaka , Suzuki Yoshiyuki , Saitoh Satoshi , Kobayashi Masahiro , Akuta Norio , Someya Takashi , Koyama Rikako , Hosaka Tetsuya , Sezaki Hitomi , Kobayashi Mariko , Kumada Hiromitsu
Published: December 2006

Objective: The purpose of this study was to elucidate the long-term outcome after interferon (IFN) therapy in chronic hepatitis C elderly patients. Methods: We studied the incidence of hepatocellular carcinoma (HCC) and survival probability after the initiation of IFN therapy in 500 Japanese chronic hepatitis C patients >60 years. The mean age of initiation of IFN was 63 years and the mean follow-up period was 7.4 years. Cox proportional hazard regression analysis was used to evaluate the long-term outcome after initiation of IFN therapy.Sustained virological response (SVR) was defined as negative HCV-RNA by RT-nested PCR 6 months after the completion of long-term IFN therapy. Non-response (NR) was applied to patients who did not show SVR. Hepatic fibrosis was defined as the fibrosis score (score 0–4) according to Knodell et al. Results: 140 patients (28%) had an SVR and 360 patients (72%) had an NR. 71 of 500 patients developed HCC during follow-up. The cumulative incidence of HCC was 9.6% at the 5th year, 17.4% at the 10th year, and 31.3% at the 15th year. HCC developed with significance when: (1) HCV was not cleared after IFN therapy (p < 0.0001), (2) sex was male (p < 0.0001), and (3) staging of liver fibrosis was >2 (p = 0.008). 53 of the patients died. The cumulative survival probability was 95.7% at the 5th year, 86.4% at the 10th year, and 78% at the 15th year. Patients achieved a long survival with significance when: (1) staging of liver fibrosis was 1 (p < 0.0001), (2) HCV was cleared after IFN therapy (p = 0.034), and (3) sex was female (p = 0.015). Conclusion: Chronic hepatitis C patients with clearance of HCV after IFN therapy had a significantly reduced risk of HCC appearance and achieved prolonged survival even if they are ≧60 years.
Clinical Characteristics of NonBNonC- HCC: Comparison with HBV and HCV Related HCC
Authors: Hatanaka Kinuyo , Kudo Masatoshi , Fukunaga Toyokazu , Ueshima Kazuomi , Chung Hobyung , Minami Yasunori , Sakaguchi Yasuhiro , Hagiwara Satoshi , Orino Akio , Osaki Yukio
Published: December 2006

Objective: To clarify the frequency and trends of both HBsAg and HCVAb negative hepatocellular carcinoma (NonBNonC-HCC) in all HCC, to clarify the etiology of NonBNonC-HCC, and to elucidate the clinical characteristics of NonBNonC-HCC compared with those of HBsAg-positive HCC (B-HCC) and HCVAb-positive HCC (C-HCC). Methods: A total of 2,542 patients with HCC examined at three institutions between 1991 and 2004 were categorized based on their serum viral antigen/antibody positivities, and compared between groups for the etiology, annual trend of the incidence, and clinical characteristics. Results: For the etiology, C-HCC was most prevalent, followed by B-HCC, NonBNonC-HCC, and both HBsAg and HCVAb-positive HCC (BC-HCC) in order. For survival, C-HCC had the most favorable prognosis, followed by NonBNonC-HCC, and B-HCC patients had the poorest prognosis in the three groups (C-HCC, B-HCC, and NonBNonC-HCC). In tumor-node metastasis (TNM) stages I+II, however, NonBNonC-HCC patients took the most favorable clinical course. The incidence of NonBNonC-HCC in all HCC was 5–8% from 1991 to 1998, and has increased to 10–12% since 1999. Additionally, the incidence of HBcAb-positive HCC in NonBNonC-HCC declined each year. Among NonBNonC-HCC patients, the morbidity of diabetic complications was significantly higher in HBcAb-negative patients than in HBcAb-positive patients. Conclusion: Although the incidence of NonBNonC-HCC among all HCC has an increasing trend recently, the incidence of HBcAb-positive HCC in NonBNonC-HCC has a tendency of decreasing. This fact suggest its etiology might be changing from occult HBV related HCC to unknown etiology such as nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) related HCC. The prognosis of NonBNonC-HCC was fairly good if the HCC was found in its early stage.
Analysis of Repeat Units in the R2 Region among Different Oka Varicella-Zoster Virus Vaccine Strains and Wild-Type Strains in Germany
Authors: Sauerbrei A. , Zell R. , Wutzler P.
Published: December 2006

Objective:The present study compared the number of R2 repeat units in six different Oka strains and in 54 varicella-zoster virus (VZV) wild-type strains isolated from patients with varicella or zoster in Germany. Methods:TheR2 genomic region was characterized by polymerase chain reaction and sequencing methods. Results:Five VZV Oka vaccine strains showed a number of seven 42-bp units and, in one, eight repeats were found. In 11 VZV wild-type strains isolated from patients with varicella, the copy number ranged between four and eight, and in 43 strains from zoster a similar range between four and nine copies was observed. About 80% of all strains showed between five and seven repeated units. More than one third of strains revealed seven repeats like Oka. Conclusions: The size of the R2 repeat region can also be different in single Oka vaccine strains. In German VZV wild-type strains, the R2 fragment seems to be not as variable as in Japanese wild-type strains.
Molecular Epidemiology of Hepatitis B Virus (HBV) Genotypes and Serotypes in Patients with Chronic HBV Infection in Korea
Authors: Kim Hong , Jee Young Mee , Song Byung-Cheol , Shin Jung Woo , Yang Soo Hyun , Mun Ho-Suk , Kim Hyun-Ju , Oh Eun-Ju , Yoon Jung-Hwan , Kim Yoon-Jun , Lee Hyo-Suk , Hwang Eung-Soo , Cha Chang-Yong , Kook Yoon-Hoh , Kim Bum-Joon
Published: December 2006

Objectives: Although hepatitis B virus (HBV) is endemic to Korea, no large-scale survey of HBV genotypes and serotypes based on sequence analysis has been performed. Methods: In the present study, we genotyped and serotyped HBV strains from 209 patients in two Korean regions, Seoul (107 patients) and Jeju (102 patients), an island off the southeastern Korean coast. Analyses were conducted using the direct sequencing method targeting the partial surface (S) gene (541 bp). Results: Phylogenetic analysis showed that all HBV strains from the 209 patients belonged to genotype C2 (100%). Of the 209 patients, 193 (92.3%), 12 (5.7%) and 1 (0.5%) were found to have the adr, adw and ayr serotypes, respectively. The other three strains (1.5%) showed unique serotype and were not typeable by sequence analysis. No HBV strains characteristic of Jeju island were observed. Conclusions: The extraordinary predominance of genotype C2 in chronic Korean patients, which is known to be associated with more severe liver disease than genotype B, suggests that the clinical manifestations of Korean HBV chronic patients are likely to differ from those found in other Asian countries, especially in Japan and Taiwan, where genotypes B and C coexist.
Cross-Protection against Homologous Drift Variants of Influenza A and B after Vaccination with Split Vaccine
Authors: Heckler R. , Baillot A. , Engelmann H. , Neumeier E. , Windorfer A.
Published: December 2006

The aim of this serological study was to demonstrate the extent to which antibodies react against subsequent drift variants, after vaccination with split vaccine (FluarixTM). Antibody titers have been determined by hemagglutination inhibition test (HI) against different influenza A and B drift variants in sera from three past multicenter trials. Individuals of two different age groups, i.e. 18–60 years and above 60 years, were enrolled. Vaccine components influenza A/H1N1 and influenza B of FluarixTM show a high degree of cross immunogenicity against subsequent homologous drift variants. The genetically more variable component influenza A/H3N2 shows somewhat lower protection rates. High levels of cross immunogenicity were found between the variants of influenza A/Panama/2007/99 (H3N2) and influenza A/Wyoming/3/2003 (H3N2). The results demonstrate that in situations where drift variants emerge too late to be included in the influenza vaccine formulation, the cross-protection conferred must be evaluated on a case-by-case basis.
Should the Use of Selective Serotonin Reuptake Inhibitors in Child and Adolescent Depression Be Banned?
Authors: Cohen David
Published: December 2006

Background: European and US pharmaceutical agencies have recently warned against the use of selective serotonin reuptake inhibitors (SSRIs) in child and adolescent depression. This came as a surprise to many practitioners, who had made treatment decisions based on data from pharmaceutical trials using adult samples. Method: The author reviews the recent literature relevant to the use of SSRIs in youth depression, including psychiatricclinical trials, pharmacology and drug safety data. Recommendations and rationales for the use of SSRIs in this context are offered. Results: Ten publications, comprising a total of 2,046 patients, evaluated the efficacy of four SSRIs (fluoxetine, paroxetine, sertraline and citalopram) in child and adolescent depression. It is noted that an additional 6 trials (with a total of 1,234 patients) were not reported by the industry because of a lack of efficacy or problematic side effects, including suicidal behaviors. Meta-analyses revealed no data supporting the use of SSRIs, except for fluoxetine. To formulate recommendations for clinical practice, it is necessary to examine specific issues such as (1) the link between SSRIs, depression and suicidal risk; (2) SSRI age-related specific effects, and (3) the high placebo response in child and adolescent depression. Conclusion: An SSRI prescription is still a second-line option in severe and resistant forms of youth depression. However, in children and adolescents only specialists well trained in child and adolescent psychiatry should prescribe SSRIs.
Psychotherapy of Childhood Anxiety Disorders: A Meta-Analysis
Authors: In-Albon Tina , Schneider Silvia
Published: December 2006

Background: The present study compared the efficacy of psychotherapy for childhood anxiety disorders (excluding trials solely treating post-traumatic stress disorder or obsessive-compulsive disorder). Methods: The meta-analysis included studies that met the basic CONSORT (consolidated standards of reporting trials) criteria. Several outcome variables (e.g. effect sizes, percentage of recovery) were analyzed using completer and intent-to-treat analyses during post-treatment and follow-up assessment. Twenty-four studies published by March 2005 were included in this meta-analysis. Results: In all the included studies, the active treatment condition was cognitive-behavioral. The overall mean effect of treatment was 0.86. No differences in outcome were found between individual and group treatments or child- and family-focused treatments. Follow-up data demonstrated that treatment gains were maintained up to several years after treatment. Conclusions: These findings provide evidence that anxiety disorders in children can be treated efficaciously. The gathered data support the clinical utility of cognitive-behavioral therapy in this regard. Randomized controlled trial studies investigating treatments other than cognitive-behavioral therapy are missing.
Treatment-Associated Suicidal Ideation and Adverse Effects in an Open, Multicenter Trial of Fluoxetine for Major Depressive Episodes
Authors: Perlis Roy H. , Beasley Jr. Charles M. , Wines Jr. James D. , Tamura Roy N. , Cusin Cristina , Shear Deborah , Amsterdam Jay , Quitkin Frederick , Strong Robert E. , Rosenbaum Jerrold F. , Fava Maurizio
Published: December 2006

Background: Some reports suggest that a subset of depressed patients may experience suicidality – that is increase or emergence of suicidal ideation (SI) or behavior – after initiation of an antidepressant. The time course and clinical correlates of this phenomenon have not been characterized in detail. Method: We conducted a secondary analysis of a multicenter, prospective, open, 12-week trial of fluoxetine 20 mg in outpatients with nonpsychotic major depressive episodes. Adverse effects and other clinical features associated with the emergence of suicidality, defined using item 3 of the Hamilton Depression Rating Scale, were examined using Cox regression models. Results: Among 414 subjects without SI at baseline, 59 (14.3%) reported SI on at least 1 postbaseline visit. In a Cox regression, emergence of activation and worsening of depression severity were independently associated with emergence of SI, along with female gender, younger age and having thoughts that life was not worth living prior to treatment. Treatment response and remission were significantly less likely among subjects who developed SI. Conclusions: New SI was relatively common in this trial of fluoxetine and associated with the emergence of activation and overall symptomatic worsening. Whether prophylaxis against or aggressive treatment of adverse events can decrease emergence of SI merits further study.
Perspectives of Gene Therapy in Stem Cell Tissue Engineering
Authors: Goessler Ulrich Reinhart , Riedel Katrin , Hörmann Karl , Riedel Frank
Published: December 2006

Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain or improve tissue function. It is hoped that forming tissue de novo will overcome many problems in plastic surgery associated with such areas as wound healing and the immunogenicity of transplanted tissue that lead to dysfunctional repair. Gene therapy is the science of the transfer of genetic material into individuals for therapeutic purposes by altering cellular function or structure at the molecular level. Recently, tissue engineering has been used in conjunction with gene therapy as a hybrid approach. This combination of stem-cell-based tissue engineering with gene therapy has the potential to provide regenerative tissue cells within an environment of optimal regulatory protein expression and would have many benefits in various areas such as the transplantation of skin, cartilage or bone. The aim of this review is to outline tissue engineering and possible applications of gene therapy in the field of biomedical engineering as well as basic principles of gene therapy, vectors and gene delivery.
Coated Glass and Vicryl Microfibers as Artificial Axons
Authors: Howe Charles L.
Published: December 2006

The complex interactions that occur between oligodendrocytes and axons during the process of central nervous system myelination and remyelination remain unclear. Elucidation of the cell-biological and -biochemical mechanisms supporting myelin production and elaboration requires a robust in vitro system that recapitulates the relationship between axons and oligodendrocytes in a manner that is open to molecular dissection. We provide evidence for an artificial axon culture system in which we observed oligodendrocytes extending large plasma membrane projections that frequently completely ensheathed fibers coated with a variety of extracellular matrix molecules. These membrane projections varied in extent and thickness depending upon the substrate and upon the diameter of the coated fiber. Matrigel-coated glass microfibers were found to support the development of thick membrane sheaths that extended for hundreds of microns and exhibited many features suggestive of the potential for true myelin deposition. Likewise, Matrigel-coated Vicryl fibers supported plasma membrane extensions that covered extremely large surface areas and occasionally wrapped the coated Vicryl fibers in more than one membrane layer. Our findings suggest that the deposition of molecular cues onto glass or polymer fibers either via adsorption or chemical modification may be a useful tool for the discovery or validation of axonal factors critical for myelination and remyelination. Herein, we provide evidence that polyglactin 910 and glass microfibers coated with adhesion factors may provide a reasonable system for the in vitro analysis of myelination, and may eventually serve a role in engineering artificial systems for neural repair.
Regulation of Proopiomelanocortin Gene Transcription during Single and Repeated Immobilization Stress
Authors: Noguchi Tohru , Makino Shinya , Maruyama Hiroshi , Hashimoto Kozo
Published: December 2006

We have previously reported that repeated immobilization produces persistent activation of the hypothalamic-pituitary-adrenocortical axis in rats. In an attempt to assess whether any adaptational responses occur at the pituitary level, we examined the detailed time courses of proopiomelanocortin (POMC) gene transcription in the anterior pituitary (AP) in comparison with those of corticotropin-releasing hormone (CRH) gene transcription in the hypothalamic paraventricular nucleus (PVN) during single and repeated immobilization using both intronic and exonic probes. During single immobilization, there was a robust and rapid increase in both CRH heteronuclear RNA (hnRNA) in the PVN and POMC hnRNA in the AP, together with a slower increase in CRH mRNA, but no significant increase in POMC mRNA. Single immobilization also caused significant increases in the plasma concentrations of both ACTH and corticosterone. Daily immobilization for 6 days increased the basal levels of CRH hnRNA and CRH mRNA in the PVN and POMC mRNA in the AP. Both CRH hnRNA and POMC hnRNA responded rapidly to a final episode of acute immobilization on day 7, whereas the peak values of CRH hnRNA and POMC hnRNA after 15 min of the final stress were smaller than those during single immobilization. In contrast to single stress, CRH mRNA did not change significantly, whereas POMC mRNA robustly increased after the final immobilization on day 7. Plasma ACTH increased to a similar degree to single stress, but its initial increase at 5 min was significantly higher than that during single immobilization. The increase in the plasma corticosterone concentration was higher during final immobilization than during single stress. These results suggest that, in response to the hypothalamic drive during repeated immobilization stress, pituitary corticotrophs are capable of upregulating the basal and stress-induced POMC mRNA levels via increased efficiency of the posttranscriptional processing of the hnRNA and/or increased mRNA stability.
Contribution of Magnetic Resonance Imaging in Non-Tumoral Hypopituitarism in Children
Authors: Garel Catherine , Léger Juliane
Published: December 2006

Background: Magnetic resonance imaging (MRI) is of paramount importance for evaluating the hypothalamo-pituitary axis in children. Methods: We summarize the main points of the MRI technique, and describe the normal appearance of the hypothalamo-pituitary axis as a function of age and pubertal status. The most frequent causes of non-tumoral hypopituitarism include anterior pituitary deficiency (growth hormone deficiency may be isolated or associated with other anterior pituitary hormone deficiencies, with or without other malformations, and related to a known genetic abnormality in some cases), isolated hypogonadotropic hypogonadism and posterior pituitary deficiency with or without anterior pituitary hormone deficiency (central diabetes insipidus may be observed without tumor development). Results: We describe in detail the appearance of the adenohypophysis, the pituitary stalk and the neurohypophysis, correlations with hormone deficiencies, the abnormalities that may be associated and progression over time for each condition. Conclusion: An accurate description of hypothalamo-pituitary axis abnormalities is necessary for accurate diagnosis and prognosis evaluation, with certain features suggestive of particular diseases and some prognostic data correlated with phenotype.
Clinical Characteristics of a Dutch DFNA9 Family with a Novel COCH Mutation, G87W
Authors: Pauw Robert J. , Collin Rob W.J. , Huygen Patrick L.M. , Hoefsloot Lies H. , Kremer Hannie , Cremers Cor W.R.J.
Published: December 2006

The present study aims to report audiological and vestibular characteristics of a Dutch DFNA9 family with a novel mutation, G87W, in the LCCL domain of COCH. From the family with the novel G87W COCH mutation audiometric data were collected and analyzed longitudinally. Results were compared with those obtained in previously identified P51S COCH mutation carriers (n = 74) and with those obtained in G88E mutation carriers. Special attention was also given to a comparison of age-related features, such as progressive hearing loss and vestibular impairment. A novel mutation (G87W) in COCH is indicative of hearing impairment and vestibular dysfunction in the present family. Pure-tone thresholds, phoneme recognition scores, and vestibular responses of the G87W mutation carriers were essentially similar to those previously established in the P51S and G88E mutation carriers. Deterioration of hearing and vestibular function in the G87W mutation carriers started at the age of 43 years. Remarkably, similar to G88E mutation carriers, the proportion of patients over 40 years of age who developed complete vestibular areflexia was significantly lower for the G87W mutation carriers than for the P51S mutation carriers. In conclusion, the phenotype associated with the novel COCH (G87W) mutation is largely similar to that associated with the P51S and G88E mutation carriers. However, subtle differences in terms of onset age and rate of progression seem to exist.
Decreased Expression of Breast Cancer Resistance Protein in the Duodenum in Patients with Obstructive Cholestasis
Authors: Zimmermann Christian , Hruz Petr , Gutmann Heike , Terracciano Luigi , Beuers Ulrich , Lehmann Frank , Beglinger Christoph , Drewe Juergen
Published: December 2006

Background/Aims: The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis. Methods: Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry. Results: We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%. Conclusions: BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies.
Tension-Free Vaginal Tape for the Treatment of Stress Urinary Incontinence in Geriatric Patients
Authors: Touloupidis S. , Papatsoris A.G. , Thanopoulos C. , Charalambous S. , Giannakopoulos S. , Rombis V.
Published: December 2006

Objective: To evaluate the safety and efficacy of tension-free vaginal tape (TVT) for the treatment of stress urinary incontinence (SUI) in geriatric patients. Patients and Methods: Fifty-one women, aged 65–80 (mean 72.3) years, underwent a TVT procedure for genuine SUI from 2001 to 2004. A urodynamic test together with uroflowmetry were performed. The patients’ SUI bother score was assessed using a visual analog scale (VAS). Results: The mean operative time was 25 (range 14–29) min and mean hospitalization time was 1.2 (range 1–2) days. Bladder perforation occurred in 3 cases (5.8%) and was managed conservatively. Pre- and postoperative maximum flow rate were not significantly different (p > 0.05). The patients’ SUI bother score estimated by the VAS was statistically significantly improved (p < 0.0001). After a mean follow-up of 35.6 (range 14–60) months, 49 patients (96%) had no SUI, while 2 patients (3.9%) had persistent SUI. Also, during the follow-up 5 patients (9.8%) were diagnosed with de novo urgency due to detrusor overactivity and 1 patient (1.9%) had persistent dysuria that was resolved with urethrolysis. Conclusions: SUI in elderly women can be safely treated with the TVT procedure in the vast majority of the patients. However, bladder perforation during surgery and de novo urgency postoperatively should be taken into account.
Vitamin D Analogs Modulate the Expression of Plasminogen Activator Inhibitor-1, Thrombospondin-1 and Thrombomodulin in Human Aortic Smooth Muscle Cells
Authors: Wu-Wong J. Ruth , Nakane Masaki , Ma Junli
Published: December 2006

Background/Aims: Plasminogen activator inhibitor-1 (PAI-1), thrombospondin-1 (THBS1) and thrombomodulin (TM) are involved in atherothrombosis. Vitamin D receptor agonists (VDRAs) provide survival/cardiovascular benefits for chronic kidney disease patients. Methods: The effects of VDRAs on regulating PAI-1, THBS1 and TM in human aortic smooth muscle cells (SMC) and endothelial cells (EC) were studied. Results: In SMC, paricalcitol and calcitriol downregulated the expression of PAI-1 mRNA and protein in a dose-dependent manner (EC50 = 0.7 and 4.4 nM, respectively). Both drugs also downregulated THBS1 mRNA and protein (EC50 = 1.6 and 3.9 nM, respectively). In contrast, paricalcitol and calcitriol upregulated TM mRNA and protein (EC50 = 28.9 and 25.5 nM, respectively). EC did not express VDR, and VDRAs failed to induce CYP24A1, a VDR target gene. The effect of paricalcitol on THBS1 in SMC was blocked by cycloheximide, while its effect on TM and CYP24A1 was not affected, suggesting that the regulation of THBS1 by VDR may be mediated through intermediate factors, but that TM is likely a direct target of VDR. Conclusion: VDR may play a role in atherothrombosis via regulation of PAI-1, THBS1 and TM.
Investigation of the Mechanisms Underlying the Gastroprotective Effect of Nicorandil
Authors: Ismail H.A.F. , Khalifa M.M.A. , Hassan M.K. , Ashour O.M.
Published: December 2006

Aim: This study investigated possible mechanisms underlying the gastroprotective effect of nicorandil on experimentally-induced gastric lesions in rats. Methods: Rats were randomly assigned to vehicle-, nicorandil (10 mg/kg)-, glibenclamide (6 mg/kg)-, nicorandil + glibenclamide- and cimetidine-pretreated groups, in addition to non-stressed control group, to demonstrate whether the KATP channel opening contributed to nicorandil’s gastroprotection. Lesions were induced by water immersion-restraint stress (WIRS) and ulcer indices were determined. Gastric juice parameters (pH, acid output, pepsin and mucin concentrations) were determined. Another set of rats was divided into control, saline-pretreated and nicorandil (10 mg/kg)-pretreated groups. Rats underwent WIRS and their stomachs were used for determination of gastric mucosal lipid peroxides, histamine, PGE2, and total nitrites levels. Results: Nicorandil displayed significant protection against gastric lesions formation, abolished by concomitant administration of glibenclamide. Nicorandil significantly reduced gastric acid and pepsin secretion, but upon coadministration with glibenclamide, these effects were blocked. Additionally, nicorandil significantly reduced gastric mucosal lipid peroxides and total nitrites, but did not affect PGE2 and histamine levels. Conclusion: Results confirm a gastroprotective effect for nicorandil, the mechanism of which comprises KATP channel opening, free radical scavenging, decrease of pepsin and acid secretion and prevention of the detrimental rise in nitric oxide during WIRS.
Alterations of Cell Adhesion Molecules in Human Glomerular Endothelial Cells in Response to Nephritis-Associated Plasminogen Receptor
Authors: Khan Fahima , Yamakami Kazuo , Mahmood Javed , Li Bing , Kikuchi Tamami , Kumagai Naoki , Morioka Tetsuo , Yoshizawa Nobuyuki , Oite Takashi
Published: December 2006

Background: Acute post-streptococcal glomerulonephritis (APSGN) is induced by glomerular deposition of nephritogenic streptococcal antigen-antibody complexes. Recently, a streptococcal antigen, nephritis-associated plasminogen receptor (NAPlr) was purified from ruptured streptococcal cell supernatants (RCS). However, the cellular and molecular mechanisms of NAPlr action on the glomerular vas culature are still unknown. Methods: Expression of cell adhesion molecules were measured by cellular ELISA (enzyme-linked immunosorbent assay), immunofluorescence microscopy and Western blot analysis. Results: RCS and NAPlr significantly decreased the PECAM-1 expression in human glomerular endothelial cells (HGECs) as compared to that in the control cells. Plasminogen treatment reversed the RCS or NAPlr-induced decrease of PECAM-1 expression and increase of MCP-1 expression. Immunofluorescent microscopy and Western blot analysis also showed that PECAM-1 expression in HGECs was downregulated upon treatment with RCS or NAPlr and this effect was reversed by plasminogen treatment. Furthermore, we found that tumor necrosis factor-α production in culture medium of HGECs was increased at the lower level when the culture system was treated with RCS. Conclusion: RCS and NAPlr modulated PECAM-1 expression and MCP-1 production in HGECs, indicating the involvement of NAPlr in inflammatory cell accumulation in glomerular tufts and functional abnormality of glomerular microvasculature such as hyperpermeability.
Aspiration Rate following Nonsurgical Therapy for Laryngeal Cancer
Authors: Nguyen Nam P. , Moltz Candace C. , Frank Cheryl , Vos Paul , Millar Carrie , Smith Herbert J. , Lee Howard , Karlsson Ulf , Nguyen Phuc D. , Martinez Tomas , Nguyen Ly M. , Sallah Sabah
Published: December 2006

The aim of this study was to evaluate the aspiration rate following nonsurgical therapy, i.e. chemoradiation or radiation alone for laryngeal cancer. Modified barium swallow was performed in 43 patients who complained of dysphagia following chemoradiation (n = 22) or radiation alone (n = 21) for laryngeal cancer. Patients were selected if they were cancer free at the time of the swallowing study. Dysphagia severity was graded on a scale of 1–7. Patients were grouped according to the dysphagia severity: no aspiration (grade 1–4), and severe (grade 5–7). Mean and median dysphagia grades were 4.4/5 and 3.5/3 for chemoradiation and radiation, respectively. Aspiration occurred in 12 patients (54%) of the chemoradiation group and 7 (33%) of the radiation alone group (p = 0.13). There was a higher proportion of patients with large tumor (T3–T4) in the chemoradiation group (64%) compared to the radiation group (5%) (p = 0.0001). Aspiration is a significant source of morbidity in patients treated for laryngeal cancer with chemoradiation or radiation alone. Aspiration occurred in both groups. Although the observed difference in aspiration rates did not achieve statistical significance, the higher aspiration rate in the chemoradiation group may be due to a higher proportion of large tumors, to the additional toxic effect of chemotherapy, or to the small number of patients in both groups. Diagnostic studies such as modified barium swallow should be part of future laryngeal cancer prospective studies to assess the prevalence of aspiration as it may be silent.
Comparative Study of Three Amniotic Fluid Markers in Premature Rupture of Membranes: Prolactin, Beta Subunit of Human Chorionic Gonadotropin, and Alpha-Fetoprotein
Authors: Shahin Maha , Raslan Hanan
Published: December 2006

Objective: To evaluate whether prolactin, α-fetoprotein (AFP) or B-human chorionic gonadotropin (BHCG) is the most effective marker in vaginal fluid for diagnosing prelabor rupture of membranes (PROM). These proteins are present in amniotic and vaginal fluid and have been reported to be potent markers of PROM, but have not been used clinically nor compared to each other. Study Design: A total of 100 pregnant women between 28 and 37 weeks of gestation were recruited for the study. Patients were divided into 2 groups. The first group consisted of 50 pregnant women diagnosed with ruptured membranes. The second group consisted of 50 normal pregnant women seen during routine antenatal clinic visit (control) group. All women underwent speculum examination aiming to sample prolactin, BHCG and AFP in the vaginal fluid. Ultrasonographic examination for gestational age and amniotic fluid index measurement was performed. The electrochemoluminescence (ECLIA) method was used for quantitative measurement of the three proteins (the total duration of the assay was 18 min). Results: Vaginal fluid concentrations of the three markers were significantly higher in the PROM group than in the control group (p < 0.001). Receiver operator curve analysis indicated that AFP had 94% specificity, sensitivity, positive and negative predictive values, and efficiency. The other two markers have lower specificity, sensitivity, positive and negative predictive values, and efficiency: 70, 76, 71.7, 74.5 and 73% for prolactin and 72, 84, 75, 81.8 and 78% for BHCG, respectively. Conclusion: This work demonstrates that of the three markers investigated AFP has the highest diagnostic performance. Using the ECLIA method it can be an ideal marker for diagnosing PROM particularly in equivocal cases. The technique could be introduced into laboratory tests to meet clinical needs.
Affective Disorders in Motor Neuron Disease: A Population-Based Study
Authors: Patten Scott B. , Svenson Lawrence W. , White Christopher M. , Khaled Salma M. , Metz Luanne M.
Published: December 2006

Several studies have suggested that there may be an increased prevalence of affective disorders in people with motor neuron disease (MND). However, the literature is inconsistent, possibly because of small sample sizes in the existing studies. The Canadian province of Alberta has a universal health care system in which physician contacts are recorded along with ICD-9-CM diagnostic codes. In this analysis, diagnostic codes indicative of MND and affective disorders were used. Stratified analysis and logistic regression were used in the analysis. There were 336 cases of MND leading to a prevalence of 14.5 per 100,000 in provincial residents ≧20 years old. Affective disorders were identified in 8.6% of the total population during the same year. The crude odds ratio for affective disorders in MND was 2.3 (95% CI = 1.7–3.0). However, the prevalence of affective disorders declined with increasing illness duration.
Prevalence of Multiple Sclerosis in Bogotá, Colombia
Authors: Toro Jaime , Sarmiento Olga L. , Díaz del Castillo Adriana , Satizábal Claudia Liliana , Ramírez Jhon Darwin , Montenegro Ana Cristina , Góngora María Carolina , Quiñones Jairo Alonso , Díaz Andrés , Tobón Alejandro
Published: December 2006

Among Latin American countries, Colombia is considered a low-risk area for multiple sclerosis (MS) and no studies on MS prevalence have been conducted in any of the country’s large urban settings. To fill this gap and assess the prevalence of MS in Bogotá as of December 31, 2002, this study reviewed the clinical records of patients diagnosed with MS in most Bogotá hospitals. This review produced a sample of 296 patients with an MS diagnosis whose reliability was verified by a neurologist with expertise in MS. The total prevalence rate identified for December 2002 was 4.41/100,000 inhabitants (95% CI 3.9–4.9), including a rate of 5.98/100,000 (95% CI 5.2–6.8) for women and 2.71/100,000 (95% CI 2.2–3.3) for men (differences measured at p < 0.001). The prevalence estimates for Bogotá, confirm the city’s status as a low-risk area for MS.
Stroke Associated with Diabetes among Canadians: Sex and Age Differences
Authors: Lin Mei , Chen Yue , Sigal Ronald J.
Published: December 2006

Objective: To determine the age and sex variations in the relationship between diabetes and stroke. Methods: This analysis was based on data from 61,327 Canadians ≧45 years of age who participated in the Canadian Community Health Survey in 2000–2001. Logistic regression analysis was conducted to evaluate the association between diabetes and stroke, and effect modification by age and sex. Results: The association between diabetes and stroke was stronger in the 45- to 64-year age group than the ≧65 year age group in men but not in women. The increased risk of stroke associated with diabetes was much stronger in men (adjusted OR = 3.86, 95% CI = 2.44–6.13) than in women (adjusted OR = 1.63, 95% CI = 0.88–2.99), and this difference was only observed in the younger age group. The results were similar after further adjustment for hypertension and heart disease. Conclusions: There is a stronger association between stroke and diabetes in men than in women 45–64 years of age, suggesting men are more susceptible to stroke than women when they have diabetes.
Association Analysis of Genetic Polymorphisms in the CDC2 Gene with Late-Onset Alzheimer Disease
Authors: Liang Xueying , Schnetz-Boutaud Nathalie , Bartlett Jackie , Anderson Brent M. , Gwirtsman Harry , Schmechel Don , Carney Regina , Gilbert John R. , Pericak-Vance Margaret A. , Haines Jonathan L.
Published: December 2006

Background: Alzheimer disease (AD) is a complex neurodegenerative disorder resulting from multiple genetic and non-genetic factors. Linkage studies indicated that chromosome 10 has at least one locus for this disease. The cell division cycle 2 (CDC2) gene, which is close to one of the linkage regions, has previously been associated with the risk of AD with an odds ratio of 1.78. Biologically, CDC2, which is involved in paired helical filament-tau formation, is thought as a candidate gene in AD. Methods: In this study, six single nucleotide polymorphisms spanning the entire gene were selected and examined for association for late-onset AD (LOAD) in two large independent datasets. A family-based dataset including 1,337 Caucasian discordant sib pairs and an independent dataset of 745 Caucasian cases and 998 controls for LOAD were used. Family-based association tests and logistic regression conditional on the apolipoprotein E genotype and sex were applied to association study in family-based and case-control datasets, respectively. Results: Neither dataset demonstrated any association with LOAD in our samples with all p values >0.16. Conclusion: Our results suggest that if any contribution of common genetic variants in CDC2 to the risk of developing AD exists, it is likely to be very small.
Invasive Sphenoidal Aspergillosis: Successful Treatment with Sphenoidotomy and Voriconazole
Authors: Baumann Ariane , Zimmerli Stefan , Häusler Rudolf , Caversaccio Marco
Published: December 2006

Treatment of invasive sphenoidal aspergillosis is surgical, followed by antifungal therapy, mostly amphotericin B. To optimize the adjuvant antifungal treatment, which is often limited by severe side effects, the new triazole antifungal agent voriconazole with broad coverage of fungal pathogens including Aspergillus was investigated in a study of 4 patients with clinical, radiological and histological signs of invasive sphenoidal aspergillosis. They first underwent endoscopic sphenoidotomy with drainage and extraction of the fungal mass. Postoperatively, 2 patients were immediately treated with voriconazole. Two patients initially received amphotericin B; but this treatment had to be stopped because of acute renal toxicity. Finally, all patients were treated orally with 200 mg voriconazole twice a day for 12–14 weeks. After this combined treatment all patients were asymptomatic and there were no endoscopic or radiological signs of residual fungal disease. The only side effects were nausea in one and transient visual disturbances in 2 other patients. In the 4 patients presented and treated, voriconazole was shown to be effective and less toxic than amphotericin B in adjuvant treatment of invasive sphenoidal aspergillosis.
Sphingosine-1-Phosphate Stimulates the Functional Capacity of Progenitor Cells by Activation of the CXCR
4
-Dependent Signaling Pathway via the S1P
3
Receptor
Authors: Walter Dirk H. , Rochwalsky Ulrich , Reinhold Johannes , Seeger Florian , Aicher Alexandra , Urbich Carmen , Spyridopoulos Ioakim , Chun Jerold , Brinkmann Volker , Keul Petra , Levkau Bodo , Zeiher Andreas M. , Dimmeler Stefanie , Haendeler Judith
Published: December 2006

Objective—

Sphingosine-1-phosphate (S1P) is a bioactive lipid, which influences migration and proliferation of endothelial cells through activation of S1P receptors and has been shown to support SDF-1 induced migration and bone marrow homing of CD34
+
progenitors.

Methods and Results—

Here, we show that incubation of patient-derived endothelial progenitor cells (EPCs) with S1P or its synthetic analog FTY720 improved blood flow recovery in ischemic hind limbs. Likewise, recovery of blood flow was dramatically reduced after induction of hindlimb ischemia in mice deficient for the S1P receptor 3 (S1P
3
). S1P
3
−/−
bone marrow–derived mononuclear cells (BMCs) failed to augment neovascularization after hind limb ischemia. Of note, treatment of BMCs derived from S1P
3
−/−
mice with S1P did not rescue blood flow recovery. Mechanistically, S1P and FTY720 induced phosphorylation of CXCR
4
, activated the Src kinase, and stimulated phosphorylation of JAK2. The contribution of CXCR
4
for S1P-mediated effects was further supported by the findings that S1P preincubation failed to stimulate invasion capacity and in vivo blood flow recovery of BMCs from CXCR
4
+/−
mice. The activation of CXCR
4
was dependent on the Src kinase family as demonstrated by preincubation with the Src inhibitor PP2. The activation of the CXCR
4
signaling by S1P is mediated via the S1P
3
receptor, since S1P-induced Src phosphorylation was abrogated in EPC from S1P
3
−/−
mice.

Conclusions—

S1P agonists might serve as sensitizers of CXCR
4
-mediated signaling and may be applied in clinical progenitor cell therapy to improve EPC or BMC function in patients with coronary artery disease.