bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity and Reliability of the Turkish Migraine Disability Assessment (MIDAS) Questionnaire
Authors: Ertaş Mustafa , Siva Aksel , Dalkara Turgay , Uzuner Nevzat , Dora Babür , İnan Levent , İdiman Fethi , Sarica Yakup , Selçuki Deniz , Şirin Hadiye , Oğuzhanoğlu Atilla , İrkeç Ceyla , Özmenoğlu Mehmet , Özbenli Taner , Öztürk Musa , Saip Sabahattin , Neyal Münife , Zarifoğlu Mehmet , MIDAS group Turkish 
Published: August 2004

Objectives.—The aim of this study is to assess the comprehensibility, internal consistency, patient‐physician reliability, test‐retest reliability, and validity of Turkish version of Migraine Disability Assessment (MIDAS) questionnaire in patients with headache.Background.—MIDAS questionnaire has been developed by Stewart et al and shown to be reliable and valid to determine the degree of disability caused by migraine. Design and Methods.—This study was designed as a national multicenter study to demonstrate the reliability and validity of Turkish version of MIDAS questionnaire. Patients applying to 17 Neurology Clinics in Turkey were evaluated at the baseline (visit 1), week 4 (visit 2), and week 12 (visit 3) visits in terms of disease severity and comprehensibility, internal consistency, test‐retest reliability, and validity of MIDAS. Since the severity of the disease has been found to change significantly at visit 2 compared to visit 1, test‐retest reliability was assessed using the MIDAS scores of a subgroup of patients whose disease severity remained unchanged (up to ±3 days difference in the number of days with headache between visits 1 and 2).Results.—A total of 306 patients (86.2% female, mean age: 35.0 ± 9.8 years) were enrolled into the study. A total of 65.7%, 77.5%, 82.0% of patients reported that “they had fully understood the MIDAS questionnaire” in visits 1, 2, and 3, respectively. A highly positive correlation was found between physician and patient and the applied total MIDAS scores in all three visits (Spearman correlation coefficients were R= 0.87, 0.83, and 0.90, respectively, P < .001). Internal consistency of MIDAS was assessed using Cronbach's α and was found at acceptable (>0.7) or excellent (>0.8) levels in both patient and physician applied MIDAS scores, respectively. Total MIDAS score showed good test‐retest reliability (R= 0.68). Both the number of days with headache and the total MIDAS scores were positively correlated at all visits with correlation coefficients between 0.47 and 0.63. There was also a moderate degree of correlation (R= 0.54) between the total MIDAS score at week 12 and the number of days with headache at visit 2 + visit 3, which quantify headache‐related disability over a 3‐month period similar to MIDAS questionnaire.Conclusion.—These findings demonstrated that the Turkish translation is equivalent to the English version of MIDAS in terms of internal consistency, test‐retest reliability, and validity. Physicians can reliably use the Turkish translation of the MIDAS questionnaire in defining the severity of illness and its treatment strategy when applied as a self‐administered report by migraine patients themselves.
New medication treatment options for bipolar disorders
Authors: Ketter T. A. , Wang P. W. , Nowakowska C. , Marsh W. K. 
Published: August 2004

Objective:  To assess new treatment options for bipolar disorders.Method:  Controlled studies of new treatments for bipolar disorders were identified by computerized searches and reviews of scientific meeting proceedings, and were compiled by drug category.Results:  Two main categories of medications, newer anticonvulsants and newer antipsychotics, are yielding emerging new treatment options for bipolar disorders. Newer anticonvulsants have diverse psychotropic profiles, and although not generally effective for acute mania, may have utility for other aspects of bipolar disorders (e.g. lamotrigine for maintenance or acute bipolar depression), or for comorbid conditions (e.g. gabapentin for anxiety or pain, topiramate for obesity, bulimia, alcohol dependence, or migraine, and zonisamide for obesity). In contrast, newer antipsychotics generally appear effective for acute mania, and some may ultimately prove effective in acute depression (e.g. olanzapine combined with fluoxetine, quetiapine) and maintenance (e.g. olanzapine).Conclusion:  Emerging research is yielding new treatment options for bipolar disorders and comorbid conditions.
Scale matters: the need for a Bipolar Depression Rating Scale (BDRS)
Authors: Berk M. , Malhi G. S. , Mitchell P. B. , Cahill C. M. , Carman A. C. , Hadzi‐Pavlovic D. , Hawkins M. T. , Tohen M. 
Published: August 2004

Objective:  To briefly review the clinical and biological distinctions between unipolar and bipolar depression critiquing in particular currently available depression rating scales and discuss the need for a new observer‐rated scale tailored to bipolar depression.Method:  Relevant literature pertaining to the symptomatic differences between bipolar disorder and unipolar disorder as well as their measurement using existing assessment scales was identified by computerized searches and reviews of scientific journals known to the authors.Results:  Bipolar depression is distinct from unipolar depression in terms of phenomenology and clinical characteristics. These distinguishing features can be used to identify bipolarity in patients that present with recurrent depressive episodes. This is important because current self‐report and observer‐rated scales are optimized for unipolar depression, and hence limited in their ability to accurately assess bipolar depression.Conclusion:  The development of a specific bipolar depression rating scale will improve the assessment of bipolar depression in both research and clinical settings and assist the development of better treatments and interventions.
Bipolaroids: functional imaging in bipolar disorder
Authors: Malhi G. S. , Lagopoulos J. , Owen A. M. , Yatham L. N. 
Published: August 2004

Objective:  To evaluate the literature pertaining to the use of functional magnetic resonance imaging (fMRI) in bipolar disorder research.Method:  A search for papers published in English in journals from 1984 onwards was conducted using MedLine and EMBASE with the following terms: functional neuroimaging or fMRI and depression or bipolar disorder. In addition, retrieved papers and literature known to the authors was also scrutinized for further relevant reports.Results:  The research findings from 26 articles are tabulated and the results from 10 articles dealing specifically with bipolar disorder are discussed in detail.Conclusion:  fMRI is a useful tool for investigating bipolar disorder. Preliminary studies point to trait and state abnormalities involving structures known to be associated with the generation and modulation of emotion. The patterns of fMRI activation are different to those found in healthy subjects and patients with major depression. FMRI studies are likely to provide valuable insights into the pathophysiology of bipolar disorder.
Lithium treatment in Aarhus: contributions and controversies through half a century
Authors: Vestergaard Per 
Published: August 2004

In 1954 the first of several hundred publications on the use of lithium for treatment of affective disorders, lithium's unwanted effects, and its pharmacology was authored at the Aarhus University Psychiatric Hospital, the majority with Professor, now emeritus, Mogens Schou playing the principal part. The early part of this long series of papers highlights the pharmacology of lithium with its renal excretion, low therapeutic index, and ensuing risk of intoxication, the prophylactic effect not only against manic episodes but also the depressive ones and finally the long‐term renal structural and functional impairment.Later papers present the problems related to lithium's lower effectiveness in routine clinical use, the problems of non‐adherence, the dose effect relationships, and the problems inherent to establishing effective treatment service delivery.The present priority of the Aarhus lithium group is the simple large scale pragmatic effectiveness studies in which, together with domestic and foreign collaborators, we compare the long‐term effectiveness of lithium with new promising drugs with mood stabilizing properties.The story of treatment with lithium in aarhus highlights important steps in the development of effective and comprehensive treatments for bipolar patients.
Discrepancies between clinical and postmortem diagnoses in Jamaica: a study from the University Hospital of the West Indies
Authors: Gibson T N , Shirley S E , Escoffery C T , Reid M 
Published: August 2004

Aims:It has previously been shown that the low necropsy request rate at the University Hospital of the West Indies (UHWI) in Jamaica (35.3%) results primarily from clinicians’ confidence in clinical diagnoses and laboratory investigations. This study aimed to determine the rates of discrepancy between clinical and necropsy diagnoses at the UHWI, because many previous studies from other institutions have shown persistent high rates of discrepancy, despite advances in medical investigative technology over the past several years.Methods:Data were extracted retrospectively from consecutive necropsies performed at the UHWI over a two year period. The data were analysed to determine the categories and rates of discrepancy, and to determine the relation between discrepancy rates and age, sex, type and number of diagnoses for each patient, hospital service, and length of hospitalisation.Results:Necropsies were performed on 446 patients; 348 were suitable for further analysis. The overall discrepancy rate was 48.4% and the diagnoses with the highest individual discrepancy rates were pneumonia (73.5%), pulmonary thromboembolism (68.3%), and myocardial infarction (66.7%). Males and older patients were more likely to have discrepant diagnoses. There was a high frequency of discrepancies in patients who died within 24 hours of admission, but there was no consistent relation between length of hospitalisation and discrepancy rate.Conclusions:The high discrepancy rates documented at the UHWI are similar to those reported globally. This study supports previous attestations that the necropsy remains a vital tool for determining diagnostic accuracy, despite modern modalities of clinical investigation and diagnosis.
Prognostic significance of tenascin-C expression in superficial and invasive bladder cancer
Authors: Brunner A , Mayerl C , Tzankov A , Verdorfer I , Tschörner I , Rogatsch H , Mikuz G 
Published: August 2004

Aims:Tenascin-C (Tn-C) is an extracellular matrix glycoprotein that is upregulated in malignant tumours. Tn-C promotes cell growth, cell migration, and angiogenesis. It has been suggested to be a prognostic factor in various types of malignant tumours, but there is little information on its significance in bladder cancer with regard to overall survival (OS) and recurrence free survival (RFS).Methods:Tn-C expression was studied in 106 patients with bladder cancer diagnosed between 1994 and 1997. Immunohistochemistry was performed using a monoclonal antibody against Tn-C. RFS and OS were estimated by the Kaplan–Meier method and compared by the log rank test in univariate analysis and by the Cox multistep regression method in multivariate analysis.Results:Within the mean follow up period of 126 months, patients with diffuse Tn-C staining in the tumour stroma had a significantly worse OS than those with negative staining or only moderate Tn-C expression (p  =  0.025). Patients with cytoplasmic expression of Tn-C had a significantly better OS than those without (p  =  0.001). Multivariate analysis, taking into consideration age, grade, stage, tumour associated carcinoma in situ, progression, and Tn-C staining in tumour stroma, showed that only expression of Tn-C in invasive tumour cells was an independent positive prognostic factor for OS (p  =  0.049).Conclusions:Tn-C may provide important prognostic information in bladder cancer depending on the expression pattern in the tumour stroma or cytoplasm of the tumour cells.
Presence of vascular adventitial fibroblastic cells in diffuse-type gastric carcinomas
Authors: Nakayama H , Enzan H , Miyazaki E , Kuroda N , Toi M , Hiroi M , Yasui W 
Published: August 2004

Aim:To investigate morphological changes in the tumour vessel adventitia, particularly the distribution of vascular adventitial fibroblastic cells (VAFCs)—namely, CD34 positive fibroblastic cells just outside the vascular media—in diffuse-type gastric carcinomas.Method:In total, 18 surgically resected advanced typical diffuse-type gastric carcinomas and their normal tissues were examined. Immunostaining for CD34, CD31, high molecular weight caldesmon (HCD), and cytokeratin 8 (CAM5.2) was performed to detect VAFCs. VAFCs are positive for CD34 but negative for CD31, and are located just outside the vascular media (HCD positive vascular smooth muscle bundle). The areas just outside the vascular media in the whole maximum tumour cut surface were assessed, except the tumour growing edge, which was confirmed by immunostaining with CAM5.2. CD34 positive and CD31 negative cells just outside the vascular media were defined as VAFCs.Results:VAFC containing vessels were seen in 17 of the 18 diffuse carcinoma tissues. Vessels lacking VAFCs were also detected in these 17 tumours. In contrast, all of the vessels lacked VAFCs in the remaining tumour. In the 18 samples of normal tissue, all of the vessels contained VAFCs.Conclusions:These results suggest that the presence of VAFCs is associated with the infiltration of diffuse scattered gastric carcinoma cells.
Ki-ras gene mutations, LOH of the APC and DCC genes, and microsatellite instability in primary colorectal carcinoma are not associated with micrometastases in pericolonic lymph nodes or with patients’ survival
Authors: Zauber N P , Wang C , Lee P S , Redondo T C , Bishop D T , Goel A 
Published: August 2004

Aims:The primary aim of this study was to look for possible correlations between molecular genetic changes in primary colorectal cancer and the presence or absence of micrometastases in the accompanying pericolonic lymph nodes. The secondary aim was to correlate the data on these molecular genetic changes and micrometastases with survival.Methods:One hundred and twenty five Dukes’s stage B colorectal cancers from 1989 to 1992 were analysed. The primary tumours were evaluated for Ki-ras mutation, adenomatous polyposis coli (APC) loss of heterozygosity (LOH), deleted in colon cancer (DCC) LOH, and microsatellite instability using standard molecular techniques. All available lymph nodes were immunohistochemically stained for micrometastases.Results:Micrometastases were present in 41% of patients. There were significantly more lymph nodes removed in the patients with micrometastases. Micrometastases were not associated with Ki-ras mutation, APC LOH, DCC LOH, or microsatellite instability, even when controlling for the number of lymph nodes removed. None of the molecular variables considered had a significant impact on either overall survival or on death with disease.Conclusions:There are insufficient data to justify using molecular genetic changes in primary colorectal carcinomas as prognostic markers. Micrometastases do not provide prognostic information on survival. There is value in increasing the numbers of lymph nodes removed and analysed along with the primary tumour.
Morules in endometrial carcinoma and benign endometrial lesions differ from squamous differentiation tissue and are not infected with human papillomavirus
Authors: Chinen K , Kamiyama K , Kinjo T , Arasaki A , Ihama Y , Hamada T , Iwamasa T 
Published: August 2004

Background:Squamous differentiation/squamous metaplasia is often associated with endometrial adenocarcinoma and benign lesions, such as endometrial hyperplasia and chronic endometritis. Morules have distinct histological characteristics, and are referred to as squamous metaplasia or squamoid metaplasia.Aim:To focus on the histological characteristics of morules and clarify the difference between morules and squamous differentiation.Materials/Methods:Twenty endometrioid carcinomas with morules or squamous differentiation, five adenosquamous carcinomas, and eight non-carcinomatous endometrial lesions with morules were investigated. Numerous antibodies for epithelial membrane antigen (EMA), involucrin, cytokeratins, neuropeptides, and oncofetal antigens were used for immunohistochemistry. In situ hybridisation and polymerase chain reaction were used to detect human papillomavirus (HPV).Results:The morules observed were uniform cell clusters, with no squamous differentiation. They were immunonegative for epithelial antigens including involucrin, EMA, and cytokeratins, but were positive for neurone specific enolase. A few morules were immunopositive for acetylcholine esterase, and one case was positive for somatostatin; neither oncofetal nor proliferative cell markers, including blood group A, B, and AB, or other neuropeptides were demonstrated in the morules. HPV DNA was not found in either the morules in the carcinomas or in the benign lesions. However, true squamous differentiation tissue in four endometrioid carcinomas and two adenosquamous carcinomas was HPV positive using in situ hybridisation.Conclusion:Morules are histologically distinct from squamous metaplasia/squamous differentiation tissue. Morules are thought to be neuroectodermal-like cell clusters, and are not infected with HPV. In contrast, some of the true squamous differentiation tissue was associated with HPV infection.
The phosphodiesterase PDE4B limits cAMP-associated PI3K/AKT–dependent apoptosis in diffuse large B-cell lymphoma
Authors: Smith Peter G. , Wang Fengfei , Wilkinson Kathryn N. , Savage Kerry J. , Klein Ulf , Neuberg Donna S. , Bollag Gideon , Shipp Margaret A. , Aguiar Ricardo C. T. 
Published: August 2004

Abstract
Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Advances in the treatment of this disease will require the identification of novel therapeutic targets. We previously defined an expression signature of outcome in DLBCL and found that the phosphodiesterase PDE4B was overexpressed in fatal/refractory tumors. Phosphodiesterase 4B (PDE4B) inactivates the second messenger cyclic adenosine 3′,5′ monophosphate (cAMP) and abrogates its inhibitory effects in B lymphocytes. Hence, DLBCLs that express high PDE4B levels may be resistant to cAMP-induced apoptosis, contributing to their less favorable outcome. Herein, we confirmed the risk-related expression of PDE4B in an independent series of primary DLBCLs and defined the enzyme's role in modulating cAMP-induced apoptosis in parental DLBCL cell lines or those reconstituted with wild-type or mutant PDE4B. The cAMP-mediated apoptosis of DLBCLs was largely independent of the previously described cAMP effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC), but associated with inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The central role of AKT in this process was confirmed by expressing constitutively active mutants of this kinase in DLBCL cells. Our findings highlight the important role of cAMP signaling in DLBCL and suggest that clinically relevant PDE4 and PI3K/AKT inhibitors might be useful in the treatment of DLBCL and additional B-lymphoid malignancies with increased PDE4B expression. (Blood. 2005;105:308-316)
Mycoplasma fermentans infection promotes immortalization of human peripheral blood mononuclear cells in culture
Authors: Zhang Shimin , Tsai Shien , Wu Timothy T. , Li Bingjie , Shih James W.-K. , Lo Shyh-Ching 
Published: August 2004

Abstract
Chronic infection or colonization by mycoplasma(s) could gradually and significantly alter many biologic properties of mammalian host cells in culture, including induction of malignant transformation. We examined effects of Mycoplasma fermentans infection on the continuing survival and immortality of human peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Without specific supplemental growth factors, human PBMCs normally die rapidly, with few cells other than macrophages/monocytes surviving after 2 weeks in cultures. Only occasional Epstein-Barr virus (EBV)–positive B lymphocytes would continue to proliferate and undergo spontaneous immortalization. Our present study revealed that infection of human PBMCs in culture with the incognitus and PG18 strains of M fermentans, but surprisingly not with some other strains tested in parallel, markedly enhanced the rate of EBV-positive B lymphocytes to undergo immortalization (74% vs 17%). Compared with spontaneously immortalized PBMCs, the PBMCs immortalized in cultures infected with the mycoplasmas often had prominent karyotype changes with chromosomal loss, gain, or translocations. Furthermore, many of these immortalized B lymphocytes were found to be monoclonal in nature. The in vitro findings would be of relevance to lymphoproliferative disorders that occurred in patients with immune suppression. The mycoplasma-mediated promotional effect in cell immortalization and its potential clinical implications warrant further study.
Intracellular kinetics of iron in reticulocytes: evidence for endosome involvement in iron targeting to mitochondria
Authors: Zhang An-Sheng , Sheftel Alex D. , Ponka Prem 
Published: August 2004

AbstractIn erythroid cells the vast majority of iron (Fe) released from endosomes must cross both the outer and the inner mitochondrial membranes to reach ferrochelatase that inserts Fe into protoporphyrin IX. In the present study, we developed a method whereby a cohort of 59Fe-transferrin (Tf)-laden endosomal vesicles were generated, from which we could evaluate the transfer of 59Fe into mitochondria. Iron chelators, dipyridyl or salicylaldehyde isonicotinoyl hydrazone (SIH), were able to bind the 59Fe when they were present during a 37°C incubation; however, addition of these agents only during lysis at 4°C chelated virtually no 59Fe. Bafilomycin A1 (which prevents endosome acidification) and succinylacetone (an inhibitor of 5-aminolevulinate dehydratase) prevented endosomal 59Fe incorporation into heme. Importantly, both the myosin light chain kinase inhibitor wortmannin and the calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), caused significant inhibition of 59Fe incorporation from 59Fe-Tf-labeled endosomes into heme, suggesting that myosin is required for Tf-vesicle movement. Our results reaffirm the astonishing efficiency of Tf-derived Fe utilization in hemoglobin (Hb)-producing cells and demonstrate that very little of this Fe is present in a chelatable pool. Collectively, these results are congruent with our hypothesis that a transient endosome-mitochondrion interaction mediates iron transfer between these organelles. (Blood. 2005;105:368-375)