bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Locally Advanced Prostate Cancer – The Case for Radical Prostatectomy
Authors: Hakenberg Oliver W. , Fröhner Michael , Wirth Manfred P.
Published: October 2006

The treatment of clinically locally advanced prostate carcinoma (stage cT3) remains controversial. One of the main reasons for this controversy results from the substantial staging error attached to the clinical diagnosis cT3 with overstaged T2 tumors and understaged node-positive cases. Treatment options in this situation include radical prostatectomy, external beam radiotherapy, immediate or delayed androgen deprivation treatment and the so-called ‘watchful waiting’. Acceptable and often surprisingly good tumor-specific survival rates have been reported for radical prostatectomy in pT3 series – based on good clinical case selection – approaching those of pT2 series. In lymph node-positive pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does not in lymph node-negative pT3 disease. A benefit of adjuvant external beam radiotherapy after radical prostatectomy for pT3 cases in prolonging overall survival has not been shown, despite the fact that it can prevent or delay biochemical and local recurrence. External beam radiotherapy as the only treatment for cT3 disease results in unfavorable tumor-specific survival rates, which can be significantly improved with adjuvant hormonal treatment with LHRH agonists. If, in case of advanced age and/or significant comorbidity, primary hormonal treatment is chosen, early hormonal deprivation therapy seems to offer marginal benefits in survival compared to delayed treatment.
Validity and Reliability of the Arabic Version of the National Institutes of Health Chronic Prostatitis Symptom Index
Authors: El-Nashaar AbdelRahman , Fathy Ahmad , Zeedan Ashraf , Al-Ahwany Amr , Shamloul Rany
Published: October 2006

Introduction: In order to accurately assess the extent of chronic pelvic pain syndrome (CPPS) and to objectively measure symptoms for natural history studies and to assess the outcome parameters for clinical trials, the National Institutes of Health (NIH) Chronic Prostatitis Collaborative Research Network developed and validated the NIH Chronic Prostatitis Symptom Index (NIH-CPSI). The aim of the current study was to develop and validate a fluent and comprehensive Arabic version of the NIH-CPSI. Methods: This study consisted of 80 consecutive male patients affected by CPPS and 80 healthy controls who were asked to complete the Arabic version of the NIH-CPSI. The translation was performed by a group consisting of an andrologist and professional translators. Psychometric data were collected. Results: Of the 160 subjects enrolled, 82 (50 patients and 32 controls) completed the study. The total Arabic NIH-CPSI scores and the scores of each subscale differed significantly between the two groups with good discriminant validity. The questionnaire had also a high internal consistency. Conclusion: The present study provides the Arabic version of the NIH-CPSI and recognizes it as a valid and reliable tool in the assessment of local patients with CPPS.
Is the Determination of the Soluble Interleukin-2 Receptor after Application of Interleukin-2 Receptor Antibodies Still Appropriate for Immunological Monitoring after Renal Transplantation?
Authors: Hamza Amir , Fischer Kersten , Loertzer Hagen , Fornara Paolo
Published: October 2006

Introduction: The use of monoclonal antibodies against the α-chain of the membrane-bound interleukin-2 receptor (IL-2Rα) as immune suppressants causes characteristic changes in the levels of soluble interleukin-2 receptor (sIL-2R) in serum and urine. Methods: 38 kidney transplant patients were included in this study. 28 of them received an induction therapy with the IL-2R antibody basiliximax (Simulect®) in addition to standard immunosuppression, 10 patients constituted the control group. Results: Time courses of sIL-2R levels of Simulect patients with and without complications after transplantation have been compared. It turned out that of a total of 18 cases with complications 15 cases could be identified by their elevated sIL-2R levels, which corresponds to a sensitivity of 83%. Conclusion: Acute rejection, CMV infection, extrarenal bacterial infection and pyelonephritis in the transplant all cause a significant increase of the sIL-2R level even after application of Simulect.
Are Lower Urinary Tract Symptoms Associated with Erectile Dysfunction in Aging Males of Taiwan?
Authors: Liu Chia-Chu , Huang Shu-Pin , Li Wei-Ming , Wang Chii-Jye , Wu Wen-Jeng , Chou Yii-Her , Huang Chun-Hsiung
Published: October 2006

Introduction: This study was conducted to evaluate the relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in aging males of Taiwan. Patients and Methods: A free health screening for aging males (≧45 years old) was conducted in Kaohsiung Medical University Chung-Ho Memorial Hospital in August 2004. LUTS and ED were assessed by validated symptom scales: the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function-5 (IIEF-5). The subjects also completed a health and demographics questionnaire and underwent detailed physical examination, serum prostate-specific antigen level determination, and transrectal ultrasonography. Results: The final study population consisted of 141 patients with a mean age of 59.8 years. The severity of LUTS and ED increased with age. After controlling for comorbidities, age (p < 0.001) and IPSS score (p < 0.001) were significantly associated with the IIEF-5 score. Furthermore, men with moderate to high IPSS scores were more likely to have ED as compared with those with mild symptoms after age adjustment (age-adjusted odds ratio 3.27, p = 0.002). Conclusions: ED and LUTS are highly prevalent in our study population, and this prevalence increases with age. ED is significantly associated with the severity of LUTS after controlling for age and comorbidities. These results highlight the clinical importance of evaluating LUTS in patients with ED and the need to consider sexual issues in the management of patients with benign prostatic hyperplasia.
Aberrant DNA Methylation Silences the Novel Heat Shock Protein H11 in Melanoma but Not Benign Melanocytic Lesions
Authors: Sharma B.K. , Smith Cynthia C. , Laing Jennifer M. , Rucker Dakara A. , Burnett Joseph W. , Aurelian Laure
Published: October 2006

Background: The heat shock protein H11 is silenced in melanoma cell lines, where its forced expression by demethylation with Aza-C triggers apoptosis. Objective: To examine whether H11 is silenced by aberrant DNA methylation in melanoma as compared to nevi and normal skin tissues. Methods: Cell suspensions from benign intradermal nevi, atypical nevi and malignant melanoma tissues were used in reverse-transcriptase PCR and methylation-specific PCR. Paraffin-embedded tissues were stained with H11 antibody. Results: H11 is methylated in 60–75% of melanoma and atypical nevi, but not in normal skin or most benign nevi. Methylation is inversely correlated with H11 expression. Conclusion: The heat shock protein H11 is silenced by aberrant DNA methylation in melanoma, but not benign melanocytic lesions or normal skin melanocytes. The data suggest that H11 is a promising target for the molecular therapy of melanoma.
A New Mutation of the Double-Stranded RNA-Specific Adenosine Deaminase Gene in a Family with Dyschromatosis Symmetrica Hereditaria
Authors: Liu Yan , Xiao Shengxiang , Peng Zhenhui , Chu Yonglie , Wang Junmin , Li Xiaoli , Zhou Shaona
Published: October 2006

Background: Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules localized on the back of the extremities and caused by mutations in the double-stranded RNA-specific adenosine deaminase (DSRAD) gene. Objective: To identify gene mutations of DSRAD in patients with DSH. Methods: A Chinese pedigree of typical DSH was subjected to mutation detection in DSRAD. Direct sequencing of all PCR products of the whole coding regions of DSRAD was performed to identify the mutation. Results: A missense mutation 2747G→T in the DSRAD gene was found in the affected members but not in the healthy individuals in this family and in 50 unrelated controls. Conclusion: Our study found a novel missense mutation in exon 9 of the DSRAD gene. We add new variants to the knowledge of DSRAD mutations in DSH.
Tumescent Suction Curettage in the Treatment of Axillary Hyperhidrosis: Experience in 63 Patients
Authors: Böni Roland
Published: October 2006

Background: Axillary hyperhidrosis is a common and most distressing problem, which can be addressed by a variety of treatment modalities. Objective: To assess the value of tumescent suction curettage in the treatment of axillary hyperhidrosis. Methods: 63 patients (39 female, 25 male; mean age 30.3 ± 7.6 years) with axillary hyperhidrosis were enrolled in the study. All patients were treated in an outpatient setting with tumescent suction curettage of the axillary cavity, using two entry sites. The results were evaluated with the iodine-starch test after 4 weeks and after 6 months. Two years after the procedure, patient satisfaction was evaluated as ‘satisfied’, ‘partially satisfied’ or ‘dissatisfied’. Results: None of the patients had early postoperative complications of infection or seroma. All patients had a marked reduction of hyperhidrosis after 4 weeks, confirmed by the iodine-starch test. After 6 months, 15 patients had high sweat rates and asked for repeat surgery. Two years after the procedure, 49 patients were satisfied, 11 patients were partially satisfied and 3 patients were dissatisfied. Conclusion: Tumescent suction curettage is a safe and effective treatment of axillary hyperhidrosis resulting in a high level of patient satisfaction. Some patients will need repeat surgery. Suction curettage, however, should not be used as the first line of treatment in axillary hyperhidrosis.
A Case of Vulvar Pyoderma Gangrenosum Associated with Collagenous Colitis
Authors: Roé E. , Dalmau J. , García-Navarro X. , Corella F. , Monfort D. , Busquets D. , Ribé A. , Delgado E. , Alomar A.
Published: October 2006

Pyoderma gangrenosum is a reactive inflammatory dermatosis which belongs to the spectrum of neutrophilic dermatoses. Due to a lack of diagnostic criteria, pyoderma gangrenosum is mainly a diagnosis of exclusion. It is rarely observed on the perineum, and vulvar involvement is even less frequent. Collagenous colitis is an idiopathic inflammatory colonic disease that is included in the microscopic colitides. The colonic mucosa and the crypt architecture are preserved but histologic alterations are found. We describe a case of collagenous colitis associated with vulvar pyoderma gangrenosum that improved spectacularly with cyclosporine 3 mg/kg/day and the twice-daily application of topical tacrolimus 0.1%.
Angioma Serpiginosum Arranged in a Systematized Segmental Pattern Suggesting Mosaicism
Authors: Chen WenChieh , Liu Ta-Ju , Yang Yi-Chien , Happle Rudolf
Published: October 2006

In a 15-year-old Taiwanese girl, multiple purple punctate lesions arranged in a systematized, segmental pattern had developed since childhood, beginning from the right thigh and gradually progressing upwards to the right buttock, the left side of the abdomen, circumventing to the left side of the back, and extending to the right arm as well as to the posterolateral aspect of the left leg. Histopathological examination showed dilated capillaries in the uppermost part of the dermal papillae characteristic of angioma serpiginosum. The systematized, segmental and asymmetric arrangement of lesions as noted in the present case suggest that angioma serpiginosum reflects genetic mosaicism.
Music Perception with Cochlear Implants and Residual Hearing
Authors: Gfeller Kate E. , Olszewski Carol , Turner Christopher , Gantz Bruce , Oleson Jacob
Published: October 2006

Aim: The aims of this study were to examine the music perception abilities of Cochlear Nucleus Hybrid (acoustic plus electric stimulation) cochlear implant (CI) recipients and to compare their performance with that of normal-hearing (NH) adults and CI recipients using conventional long-electrode (LE) devices (Advanced Bionics: 90K, Clarion, CIIHF; Cochlear Corporation: CI24M, CI22, Contour; Ineraid). Hybrid CI recipients were compared with NH adults and LE CI recipients on recognition of (a) real-world melodies and (b) musical instruments. Patients and Methods: We tested 4 Hybrid CI recipients, 17 NH adults, and 39 LE CI recipients on open-set recognition of real-world songs presented with and without lyrics. We also tested 14 Hybrid CI recipients, 21 NH adults, and 174 LE CI recipients on closed-set recognition of 8 musical instruments playing a 7-note phrase. Results: On recognition of real-world songs, both the Hybrid recipients and NH listeners were significantly more accurate (p < 0.0001) than the LE CI recipients in the no lyrics condition, which required reliance on musical cues only. The LE group was significantly less accurate than either the Hybrid or NH group (p < 0.0001) on instrument recognition for low and high frequency ranges. Conclusions: These results, while preliminary in nature, suggest that preservation of low-frequency acoustic hearing is important for perception of real-world musical stimuli.
The Size of the Cochlea and Predictions of Insertion Depth Angles for Cochlear Implant Electrodes
Authors: Escudé Bernard , James Chris , Deguine Olivier , Cochard Nadine , Eter Elias , Fraysse Bernard
Published: October 2006

Aims: To establish normative data on the size of the basal turn of the cochlea using high-resolution computed tomography of the temporal bone in adults and children. To determine whether final insertion depth angle for a perimodiolar cochlear implant electrode varies according to cochlear size. Methods: Forty-two patients screened for cochlear anomaly using computed tomography were randomly selected from patients with otologic disease. Reconstruction of the full basal turn was performed for both ears using a 1.0-mm layer, minimum intensity projection. The largest distance from the round window to the lateral wall (distance A) and the perpendicular distance (B) were measured. Distances were averaged between ears for each individual. In addition, 15 patients were implanted with the Nucleus 24 Contour Advance electrode array using a linear insertion depth of either 17 mm (n = 9) or 19 mm (n = 6). Postoperative X-rays were analyzed using the method of Xu et al. [Am J Otol 2000;21:49–56] to obtain the insertion depth angles for individual electrodes. Results: Mean distance A was 9.23 mm (SD = 0.53, range 7.9–10.8 mm). Perpendicular distance B was significantly correlated with distance A (r2 = 0.57, p < 0.001). The mean difference in insertion depth angle between the 17 and 19 mm groups was 80°. A statistically significant correlation (r2 = 0.51) was found between distance A and the insertion depth angle for the 17 mm group. Conclusions: The cochlear size measure distance A was repeatable to within the resolution of the high-resolution computed tomography image data. The basal turn of the normally formed cochlea is variable in size. These variations in size would produce >5.0 mm variation in the length of the lateral wall to the point consistent with an insertion depth angle of 360°. Cochlear size influenced final insertion depth angles obtained for the perimodiolar Nucleus 24 Contour Advance electrode.
Acoustic plus Electric Speech Processing: Preliminary Results of a Multicenter Clinical Trial of the Iowa/Nucleus Hybrid Implant
Authors: Gantz Bruce J. , Turner Christopher , Gfeller Kate E.
Published: October 2006

Aim: This communication details the latest preliminary results from an ongoing multicenter single-subject design clinical trial of the Iowa/Nucleus Hybrid 10-mm cochlear implant. Selection criteria, surgical strategies used for hearing preservation, and the benefits of preserved residual low-frequency hearing, improved word understanding in noise, and music appreciation are described. Patients and Methods: The device has been implanted in 48 individuals with residual low-frequency hearing. Results:Hearing preservation has been accomplished in 46/48 subjects. Acoustic speech perception has also been preserved. Combined acoustic plus electric speech processing has enabled most of this group of volunteers to gain improved word understanding as compared to their preoperative hearing with bilateral hearing aids. A subset of subjects with 12 months or more experience demonstrates CNC word understanding continues to improve more than 24 months after implantation. Improved word understanding in noise is also a benefit of acoustic plus electric speech processing. Conclusions:The improvement of speech in noise and melody recognition is linked to the ability to distinguish fine pitch differences as the result of preserved residual low-frequency acoustic hearing. Both of these measures are very important in real life to the hearing impaired. Preservation of residual low-frequency hearing should be considered when expanding candidate selection criteria for standard cochlear implants.
Association of Eating Disorders with Catechol-O-Methyltransferase Gene Functional Polymorphism
Authors: Mikołajczyk Elżbieta , Śmiarowska Małgorzata , Grzywacz Anna , Samochowiec Jerzy
Published: October 2006

Aim: The aim of this study was to evaluate functional catechol-O-methyltransferase (COMT) genetic variation as a risk factor for eating disorders (ED). Method: Eighty women receiving treatment for serious ED (52 for anorexia nervosa, 28 for bulimia nervosa) and 116 age-matched females in the control group underwent COMT genotyping for polymorphism in exon 4 (codon 158). Both the low-activity allele and the high-activity allele (H) were determined. Results: The H/H genotype was twice as frequent in the ED group as in the control group (52.5% in the ED group and 25% in controls, χ2 = 15.5, d.f. = 2, p < 0.001, odds ratio = 3.343). The H/H genotype was found in 57.7% of anorexia nervosa patients (χ2 = 16.860, p < 0.001, Hardy-Weinberg equilibrium = 0.003, odds ratio = 4.202). The H allele (val) was discovered in 66.9% of ED patients in comparison to 47.8% of patients from the control group (χ2 = 13.89, p < 0.001, odds ratio = 6.088). In the anorexia group, H allele frequency was enhanced even higher (70.2 vs. 47.8%, χ2 = 14.48, p < 0.001, odds ratio = 8.175). The genotype associations in the subgroup of bulimia patients were not significant, but a trend for a higher frequency of the H allele was found (p = 0.084, odds ratio = 5.309). Conclusions: These findings seem to suggest that a turnover of catecholamines, connected with polymorphism determining high activity of COMT enzyme, is connected with the risk of ED occurrence, particularly anorexia nervosa. The risk is significantly higher for women with an allele of higher activity.
Unique Deletion in Exon 5 of SHOX Gene in a Patient with Idiopathic Short Stature
Authors: Shanske Alan L. , Puri Mala , Marshall Barbara , Saenger Paul
Published: October 2006

Background/Aim: It is known that haploinsufficiency for the SHOX gene (short-stature homeobox gene on the X chromosome) is responsible for short stature in Turner syndrome and Leri-Weill dyschondrogenesis, and it has been reported that it is responsible for upwards of 1 in 50 cases of idiopathic short stature. SHOX haploinsufficiency is also associated with various radiographic abnormalities, such as coarse trabecular pattern, short metacarpals/metatarsals with metaphyseal flaring, altered osseous alignment at the wrist, radial/tibial bowing, triangularization of the radial head, abnormal tuberosity of the humerus, and an abnormal femoral neck. Shortening and bowing of the radius and dorsal dislocation of the distal ulna characterize the Madelung deformity. These characteristic findings led us to do a study assessing the predictive value of certain radiographic features in association with genetic markers of idiopathic short stature. Methods: Here we describe a case of a Hispanic male with idiopathic short stature and Madelung deformity with a novel mutation in the SHOX gene. Results: Additional studies revealed a strong family history of short stature and the same SHOX mutation segregating from the mother. Conclusion: This case resulted in the description of a novel mutation in exon 5 (M202delA) and suggests the importance of screening for SHOX mutations in patients with idiopathic short stature with subtle radiographic abnormalities, including the components of the Madelung deformity in their bone age films.
Intrathecal Immunoglobulin G Synthesis and Brain Injury by Quantitative MRI in Multiple Sclerosis
Authors: Brandão Carlos O. , Ruocco Heloisa H. , Farias Alessandro S. , Oliveira Celina , Cendes Fernando , Damasceno Benito P. , Santos Leonilda M.B.
Published: October 2006

Objectives: It was the aim of this study to evaluate if the quantitative intrathecal immunoglobulin G (IgG) synthesis correlates with the brain atrophy and the total lesion volume (TLV) in brain magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients. Methods: A total of 50 patients with relapsing-remitting MS were included in this study. MRIs were performed and cerebrospinal fluid samples were collected during the diagnostic determination when patients were in remission without treatment. Results: At study baseline, IgG index values were elevated in 36 patients (72%), and oligoclonal IgG bands were positive in 42 of 50 patients (84%). Brain MRI was abnormal in 94% of patients, and, compared with healthy controls, brain atrophy was observed in MS patients. A positive correlation among IgG index, cerebrospinal fluid leukocyte count and TLV was observed; the Expanded Disability Status Scale correlated positively with TLV and the number of lesions, although a significant relationship between disability and brain atrophy was not demonstrated. Conclusions: Although new parameters will be necessary in longitudinal studies to characterize the axonal injury in various stages of the disease, the data suggest that the high intrathecal IgG synthesis may predict a greater brain lesion burden.
Morphological Changes in the Rat Sublingual Gland Parenchyma with Aging
Authors: Kikuchi Ken-ichiro , Aiyama Shigeo , Ikeda Rie , Sato Sumie
Published: October 2006

Background: The characteristics of mucous cells in the aging rat sublingual gland were investigated in this study. Particular attention was paid to accumulated amyloid protein and changes of the properties of the secretory granules at the histochemical and ultrastructural level. Objective: This study was designed to examine age-related morphological changes in the sublingual gland of male Wistar rats from 12 to 27 months. Methods: For light microscopy, the sublingual glands were fixed with 10% neutral-buffered formalin, embedded in paraffin, and processed for Alcian blue, Congo red, and TUNEL staining. For transmission electron microscopy, some of the samples were fixed with Karnovsky solution, postfixed with 2% osmium tetroxide, and embedded in epoxy resin for pronase treatment. Results: The sublingual gland showed slight shrinkage after 21 months. After 24 months, Congo red staining showed positive reaction to the intralobular connective tissue surrounding the terminal portions and to the interlobular connective tissue around the blood vessels and the excretory ducts. At 27 months, some of the granules in the serous demilunes had difficulty in digesting with pronase treatment. The appearance rate of TUNEL-positive cells was low in both mucous and serous portions during the observation period, though the positive cell number was higher in the serous than in the mucous portion. Conclusions: These findings indicate that the rat sublingual gland accumulates amyloid protein in the parenchyma and changes the properties of secretory granules of the acinar cells in the serous demilune with aging, though apoptosis of the parenchymal cells and the decrease of the gland weight are slight.
Hospital Admissions Associated with Traumatic Brain Injury in the US Army during Peacetime: 1990s Trends
Authors: Ivins Brian J. , Schwab Karen A. , Baker Gayle , Warden Deborah L.
Published: October 2006

Introduction: This paper examines 10-year trends in traumatic brain injury (TBI)-related hospitalization rates for active duty US Army personnel in the 1990s. It does this within the context of various factors, including enhanced injury prevention policies and changed hospital admission practices, that may have affected TBI hospitalization rates. It also compares TBI hospitalization rates in the Army to those from an age-comparable segment of the US civilian population over this time period. Methods: Crude (unadjusted) incidence rates for all active duty US Army personnel hospitalized with a TBI diagnosis from fiscal years (FY) 1990 to 1999 were calculated. Once the trends were identified, the percentage change in the overall rate, as well as the rates for different TBI severity levels, and in-hospital deaths from FY1990 and FY1999 were analyzed. Changes in age- and gender-specific rates as well as crude rates for cases with and without other injuries and cases treated in military and civilian hospitals were also analyzed. Rate ratios were used to compare aggregated 5-year TBI hospitalization rates in the Army to rates for civilians 17–49 years of age during the following time periods: 1990–1994 and 1995–1999. The rates used in the comparison were adjusted to control for differences in age and gender. Results: The overall incidence of TBI-related hospitalization in the Army decreased 75% from FY1990 to FY1999. The rates for all TBI severity levels decreased, but the rate for mild TBI decreased more than the rates for moderate and severe TBI. The rate of in-hospital deaths from TBI also decreased. Rates decreased similarly for males and females, across all age groups, as well as for cases with and without other injuries. TBI rates decreased for Army personnel treated in military hospitals but changed minimally for Army personnel treated in civilian hospitals. The Army’s TBI hospitalization rates were generally higher than civilian rates in the early 1990s but by the late 1990s, most of the Army’s rates were lower than or equal to the civilian rates. Conclusions: The incidence of TBI-related hospitalization in the active duty US Army decreased markedly (75%) during the 1990s. As a result, most of the Army’s TBI hospitalization rates were lower than civilian rates by the late 1990s. Effective injury prevention and changes in the Army population were two of the factors that likely contributed to the decrease in rates for all TBI severity levels, while changes in hospital admission practices likely contributed to the disproportionate decrease in the Army’s rates for mild TBI.
Decision Rules Guiding the Clinical Diagnosis of Alzheimer’s Disease in Two Community-Based Cohort Studies Compared to Standard Practice in a Clinic-Based Cohort Study
Authors: Bennett David A. , Schneider Julie A. , Aggarwal Neelum T. , Arvanitakis Zoe , Shah Raj C. , Kelly Jeremiah F. , Fox Jacob H. , Cochran Elizabeth J. , Arends Danielle , Treinkman Anna D. , Wilson Robert S.
Published: October 2006

We developed prediction rules to guide the clinical diagnosis of Alzheimer’s disease (AD) in two community-based cohort studies (the Religious Orders Study and the Rush Memory and Aging Project). The rules were implemented without informant interviews, neuroimaging, blood work or routine case conferencing. Autopsies were performed at death and the pathologic diagnosis of AD made with a modified version of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) criteria. We compared the positive predictive value of the clinical diagnosis in the two community-based studies to the positive predictive value of the clinical diagnosis of AD made by standard clinical practice in a clinic-based cohort study using AD pathology as the gold standard. Of 306 clinic cases with probable AD, 286 (93.5%) met CERAD neuropathologic criteria for AD; the results were comparable for those with possible AD (51 of 54, 94.4%). Of 141 study subjects with probable AD, 130 (92.2%) met CERAD neuropathologic criteria for AD; the results were lower but acceptable for those with possible AD (26 of 37, 70.3%). The results were similar in secondary analyses using alternate neuropathologic criteria for AD. The clinical diagnosis of AD can be made in community-based studies without the use of informant interviews, neuroimaging, blood work or routine case conferencing. This approach holds promise for reducing the operational costs of epidemiologic studies of aging and AD.
Auditory Brainstem Implantation to Rehabilitate Profound Hearing Loss with Totally Ossified Cochleae Induced by Pneumococcal Meningitis
Authors: Bozorg Grayeli Alexis , Kalamarides Michel , Bouccara Didier , Ben Gamra Loutfa , Ambert-Dahan Emmannuelle , Sterkers Olivier
Published: October 2006

Hearing rehabilitation by cochlear implantation is not always possible in case of total ossification after pneumococcal meningitis. We report 3 cases of postmeningitis profound hearing loss with total cochlear ossification in adults who underwent auditory brainstem implantation (Nucleus 22®, Cochlear Inc., Lane Cove, Australia) between 1999 and 2004. The postoperative follow-up period ranged from 1 to 6 years. Eleven to 15 out of 22 electrodes were activated. All patients had significant speech discrimination in the sound-only mode and an enhanced lip-reading performance with the implant. Auditory brainstem implants are an efficient means of auditory rehabilitation and may be considered in selected cases of bilateral profound hearing loss with the impossibility of cochlear implantation.
Age- and Training-Dependent Development of Arrhythmogenic Right Ventricular Cardiomyopathy in Heterozygous Plakoglobin-Deficient Mice
Authors: Kirchhof Paulus , Fabritz Larissa , Zwiener Melanie , Witt Henning , Schäfers Michael , Zellerhoff Stephan , Paul Matthias , Athai Timur , Hiller Karl-Heinz , Baba Hideo A. , Breithardt Günter , Ruiz Patricia , Wichter Thomas , Levkau Bodo
Published: October 2006

Background—

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder that causes sudden death and right ventricular heart failure in the young. Clinical data suggest that competitive sports may provoke ARVC in susceptible persons. Genetically, loss-of-function mutations in desmosomal proteins (plakophilin, desmoplakin, or plakoglobin) have been associated with ARVC. To test the hypothesis that reduced desmosomal protein expression causes ARVC, we studied the cardiac effects of heterozygous plakoglobin deficiency in mice.

Methods and Results—

Ten-month-old heterozygous plakoglobin-deficient mice (plakoglobin
+/−
) had increased right ventricular volume, reduced right ventricular function, and spontaneous ventricular ectopy (all
P
<0.05). Left ventricular size and function were not altered. Isolated, perfused plakoglobin
+/−
hearts had spontaneous ventricular tachycardia of right ventricular origin and prolonged right ventricular conduction times compared with wild-type hearts. Endurance training accelerated the development of right ventricular dysfunction and arrhythmias in plakoglobin
+/−
mice. Histology and electron microscopy did not identify right ventricular abnormalities in affected animals.

Conclusions—

Heterozygous plakoglobin deficiency provokes ARVC. Manifestation of the phenotype is accelerated by endurance training. This suggests a functional role for plakoglobin and training in the development of ARVC.
Endotoxin-Induced Cardiomyopathy and Systemic Inflammation in Mice Is Prevented by Aldose Reductase Inhibition
Authors: Ramana Kota V. , Willis Monte S. , White Michael D. , Horton Jureta W. , DiMaio J. Michael , Srivastava Deepak , Bhatnagar Aruni , Srivastava Satish K.
Published: October 2006

Background—

Sepsis is a systemic inflammatory response syndrome characterized by excessive production of inflammatory cytokines and cardiovascular collapse. Postreceptor signaling events that lead to stress responses and cytokine production are sensitive to redox changes and products of lipid peroxidation.

Methods and Results—

We tested the hypothesis that inflammatory signaling and cytokine generation during sepsis depend on the activity of the enzyme aldose reductase, which catalyzes the reduction of lipid peroxidation–derived aldehydes and their glutathione conjugates. The results of the present study show that pharmacological inhibition of aldose reductase by sorbinil or knockdown of the enzyme by small interfering RNA prevents the activation of nuclear factor-κB and the release of tumor necrosis factor-α from lipopolysaccharide-stimulated RAW264.7 or H9c2 cells. Increases in serum and cardiac cytokines in response to lipopolysaccharide challenge were suppressed by inhibition of aldose reductase. Treatment with sorbinil blunted the activation of protein kinase C, c-Jun NH
2
-terminal kinase, and p38, as well as phosphorylation of interleukin receptor–associated kinase, IκB-α, IκB kinase complex-α/β, and phospholipase-γ1 and -β1. These changes were associated with decreased myocardial nuclear factor-κB and activating protein-1 activity, prostaglandin E2 production, induction of cyclooxygenase 2, and inducible nitric oxide synthase. Sorbinil treatment also induced functional recovery in myocardial fractional shortening in vivo and preserved contractile function of isolated perfused hearts. Inhibition of aldose reductase increased survival in mice injected with lethal doses of lipopolysaccharide.

Conclusions—

The present demonstration that aldose reductase mediates endotoxin-induced inflammation and cardiomyopathy suggests that inhibition of this enzyme may be useful to attenuate maladaptive host responses and to treat acute cardiovascular dysfunction associated with endotoxic shock.
Gene Transfer of a Synthetic Pacemaker Channel Into the Heart
Authors: Kashiwakura Yuji , Cho Hee Cheol , Barth Andreas S. , Azene Ezana , Marbán Eduardo
Published: October 2006

Background—

One key element of natural pacemakers is the pacemaker current encoded by the hyperpolarization-activated nucleotide-gated channel (HCN) gene family. Although HCN gene transfer has been used to engineer biological pacemakers, this strategy may be confounded by unpredictable consequences of heteromultimerization with endogenous HCN family members and limited flexibility with regard to frequency tuning of the engineered pacemaker.

Methods and Results—

To circumvent these limitations, we converted a depolarization-activated potassium-selective channel, Kv1.4, into a hyperpolarization-activated nonselective channel by site-directed mutagenesis (R447N, L448A, and R453I in S4 and G528S in the pore). Gene transfer into ventricular myocardium demonstrated the ability of this construct to induce pacemaker activity with spontaneous action potential oscillations in adult ventricular myocytes and idioventricular rhythms by in vivo electrocardiography.

Conclusions—

Given the sparse expression of Kv1 family channels in the human ventricle, gene transfer of a synthetic pacemaker channel based on the Kv1 family has novel therapeutic potential as a biological alternative to electronic pacemakers.
Party Strength and International Trade
Authors: Hankla Charles R.
Published: October 2006

What explains the variation of trade protection across countries and years? The author argues that other things equal, democracies with strong parties will choose freer trade policies. He focuses on two aspects of party strength—organizational centralization and stable party linkages to large groups of the electorate. He contends that legislative logrolls leading to high protection are significantly less likely when parties are centralized. Furthermore, because parties with stable connections to the electorate have longer time horizons, the author argues that they will generally support more open trade policies that provide long-run economic benefits. Finally, he contends that parties linked to large electoral groups—as measured by district size—will prefer public goods such as freer trade over trade patronage. After coding a measure of party centralization developed by Cary and Shugart (1995), the author conducts a quantitative analysis of democracies from 1975-2000. His results support the theory and highlight an understudied institution in trade policy.
We Are All Comparativists Now
Authors: Lees Charles
Published: October 2006

This article asks, “What is the way forward for single-country scholarship?” It also discusses why and how single-country scholars should adopt a more comparative approach in their research. To do this, the article presents cross-sectional and longitudinal data that illustrate the relative isolation of the single-country canon, especially nondomestic single-country studies, within the wider discipline of political science. To suggest how this be redressed, the article then discusses how single-country scholarship might build bridges to the comparative approach and the benefits this might generate. The article argues that careful and innovative use of the case study research design provides the ideal means to do this.
Cortisol Levels and Longitudinal Cortisol Change as Predictors of Anxiety in Adolescents
Authors: Schiefelbein Virginia L. , Susman Elizabeth J.
Published: October 2006

Although previous research has suggested cortisol-emotion relationships, little is known regarding the effect of anxiety type on cortisol levels or relationships between anxiety and longitudinal cortisol change in adolescents. The authors examine the differential relationship of cortisol levels with generalized and social anxiety and relationships between longitudinal cortisol change and anxiety in 106 youth ages 9 through 14. Cortisol levels were assessed three times at 6-month intervals; anxiety sections of the Diagnostic Interview Schedule for Children were administered at the final occasion of measurement. In girls, cortisol exhibited positive relationships with concurrent general and social anxiety. Greater cortisol increase across the year predicted higher general and social anxiety in girls at the end of the study. No significant relationships were found in boys. Sex differences may reflect differences in the physiology of anxiety or in self-reports of emotion.
Popularity in Early Adolescence: Prosocial and Antisocial Subtypes
Authors: de Bruyn Eddy H. , Cillessen Antonius H. N.
Published: October 2006

The present study was designed to examine early adolescents’ stereotypical descriptions of two types of youth who are seen as popular by their peers. Participants were 13- to 14-year-old early adolescents (N = 287). The results indicated that early adolescents distinguished two types of popular peers: a “populistic” (popular but not necessarily well liked) type and a “prosocial-popular” (popular and well liked and accepted) type. These two types differed in terms of academic and interpersonal behaviors. Populistic adolescents were seen as relationally aggressive, stuck up, vulgar, bullies, and academically disengaged. They were also seen as leaders, influential, and arrogant more than were prosocial-popular adolescents. Adolescents in the latter group were seen as affiliative, helpful, and academically engaged. Both types of popular youth were seen as attractive and fashionable. The implications of these findings for future research on high status in the adolescent peer group are discussed.
Penetrance of eye defects in mice heterozygous for mutation of Gli3 is enhanced by heterozygous mutation of Pax6
Authors: Zaki Paulette A , Collinson J Martin , Toraiwa Junko , Simpson T Ian , Price David J , Quinn Jane C
Published: October 2006

Background

Knowledge of the consequences of heterozygous mutations of developmentally important genes is important for understanding human genetic disorders. The Gli3 gene encodes a zinc finger transcription factor and homozygous loss-of-function mutations of Gli3 are lethal. Humans heterozygous for mutations in this gene suffer Greig cephalopolysyndactyly or Pallister-Hall syndromes, in which limb defects are prominent, and mice heterozygous for similar mutations have extra digits. Here we examined whether eye development, which is abnormal in mice lacking functional Gli3, is defective in Gli3
+/- mice.

Results

We showed that Gli3 is expressed in the developing eye but that Gli3
+/- mice have only very subtle eye defects. We then generated mice compound heterozygous for mutations in both Gli3 and Pax6, which encodes another developmentally important transcription factor known to be crucial for eye development. Pax6
+/-; Gli3
+/- eyes were compared to the eyes of wild-type, Pax6
+/- or Gli3
+/- siblings. They exhibited a range of abnormalities of the retina, iris, lens and cornea that was more extensive than in single Gli3
+/- or Pax6
+/- mutants or than would be predicted by addition of their phenotypes.

Conclusion

These findings indicate that heterozygous mutations of Gli3 can impact on eye development. The importance of a normal Gli3 gene dosage becomes greater in the absence of a normal Pax6 gene dosage, suggesting that the two genes co-operate during eye morphogenesis.
Design factors that influence PCR amplification success of cross-species primers among 1147 mammalian primer pairs
Authors: Housley Donna JE , Zalewski Zachary A , Beckett Stephanie E , Venta Patrick J
Published: October 2006

Background

Cross-species primers have been used with moderate success to address a variety of questions concerning genome structure, evolution, and gene function. However, the factors affecting their success have never been adequately addressed, particularly with respect to producing a consistent method to achieve high throughput. Using 1,147 mammalian cross-species primer pairs (1089 not previously reported), we tested several factors to determine their influence on the probability that a given target will amplify in a given species under a single amplification condition. These factors included: number of mismatches between the two species (the index species) used to identify conserved regions to which the primers were designed, GC-content of the gene and amplified region, CpG dinucleotides in the primer region, degree of encoded protein conservation, length of the primers, and the degree of evolutionary distance between the target species and the two index species.

Results

The amplification success rate for the cross-species primers was significantly influenced by the number of mismatches between the two index species (6–8% decrease per mismatch in a primer pair), the GC-content within the amplified region (for the dog, GC ≥ 50%, 56.9% amplified; GC<50%, 74.2% amplified), the degree of protein conservation (R2 = 0.14) and the relatedness of the target species to the index species. For the dog, 598 products of 930 primer pairs (64.3%) (excluding primers in which dog was an index species) were sequenced and shown to be the expected product, with an additional three percent producing the incorrect sequence. When hamster DNA was used with the single amplification condition in a microtiter plate-based format, 510 of 1087 primer pairs (46.9%) produced amplified products. The primer pairs are spaced at an average distance of 2.3 Mb in the human genome and may be used to produce up to several hundred thousand bp of species-specific sequence.

Conclusion

The most important factors influencing the proportion of successful amplifications are the number of index species mismatches, GC-richness of the target amplimer, and the relatedness of the target species to the index species, at least under the single PCR condition used. The 1147 cross-species primer pairs can be used in a high throughput manner to generate data for studies on the genetics and genomics of non-sequenced mammalian genomes.
Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1genes in familial colorectal cancer predisposition
Authors: Broderick Peter , Bagratuni Tina , Vijayakrishnan Jairam , Lubbe Steven , Chandler Ian , Houlston Richard S
Published: October 2006

Background

The observation that germline mutations in the oxidative DNA damage repair gene MUTYH cause colorectal cancer (CRC) provides strong evidence that dysregulation of the base excision repair (BER) pathway influences disease susceptibility. It is conceivable that germline sequence variation in other BER pathway genes such as NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 also contribute to CRC susceptibility.

Methods

To evaluate whether sequence variants of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes might act as CRC susceptibility alleles, we screened the coding sequence and intron-exon boundaries of these genes in 94 familial CRC cases in which involvement of known genes had been excluded.

Results

Three novel missense variants were identified NEIL2 C367A, TDG3 A196G and UNG2 C262T in patients, which were not observed in 188 healthy control DNAs.

Conclusion

We detected novel germline alterations in NEIL2, TDG and UNG patients with CRC. The results suggest a limited role for NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 in development of CRC.
Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine
Authors: Meissner Peter E , Mandi Germain , Coulibaly Boubacar , Witte Steffen , Tapsoba Théophile , Mansmann Ulrich , Rengelshausen Jens , Schiek Wolfgang , Jahn Albrecht , Walter-Sack Ingeborg , Mikus Gerd , Burhenne Jürgen , Riedel Klaus-Dieter , Schirmer R Heiner , Kouyaté Bocar , Müller Olaf
Published: October 2006

The development of safe, effective and affordable drug combinations against malaria in Africa is a public health priority. Methylene blue (MB) has a similar mode of action as chloroquine (CQ) and has moreover been shown to selectively inhibit the Plasmodium falciparum glutathione reductase. In 2004, an uncontrolled dose-finding study on the combination MB-CQ was performed in 435 young children with uncomplicated falciparum malaria in Burkina Faso (CQ monotherapy had a > 50% clinical failure rate in this area in 2003). Three serious adverse events (SAE) occurred of which one was probably attributable to the study medication. In the per protocol safety analysis, there were no dose specific effects. The overall clinical and parasitological failure rates by day 14 were 10% [95% CI (7.5%, 14.0%)] and 24% [95% CI (19.4%, 28.3%)], respectively. MB appears to have efficacy against malaria, but the combination of CQ-MB is clearly not effective in the treatment of malaria in Africa.
Traditional medicinal plant use in Loja province, Southern Ecuador
Authors: Bussmann Rainer W , Sharon Douglas
Published: October 2006

This paper examines the traditional use of medicinal plants in Loja province, Southern Ecuador.

Two hundred fifteen plant species were collected, identified and their vernacular names and traditional uses recorded. This number of species indicates that the healers, market vendors and members of the public interviewed still have a very high knowledge of plants in their surroundings, which can be seen as a reflection of the knowledge of the population in general. However, the area represents only an outlier of the larger Northern Peruvian cultural area, where more than 500 species of plants are used medicinally, indicating that in Ecuador much of the original plant knowledge has already been lost.

Most plant species registered are only used medicinally, and only a few species have any other use (construction, fodder, food). The highest number of species is used for the treatment of "magical" (psychosomatic) ailments (39 species), followed by respiratory disorders (34), problems of the urinary tract (28), Fever/Malaria (25), Rheumatism (23) and nervous system problems (20).