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Terms modified by ICC Selected AbstractsDifficulties in diagnosing small round cell tumours of childhood from fine needle aspiration cytology samplesCYTOPATHOLOGY, Issue 2 2008ekArticle first published online: 18 MAR 200, iva Pohar-Marin There are four basic reasons for the difficulties in diagnosing small round cell tumours (SRCT) in childhood from fine needle aspiration cytology (FNAC) samples. First, SRCTs are rare and it is difficult for cytopathologists to obtain enough experience for rendering reliable diagnoses. Second, SRCTs are morphologically very similar. Third, many SRCTs do not have specific antigens which could be demonstrated with immunocytochemistry (ICC) or they lose them when poorly differentiated. In addition, cross reactivity exists between some SRCTs. Unstandardized performance of ICC also contributes to the difficulties due to unreliable results. Fourth, suboptimal FNAC samples add additional pitfalls. The latter may be due to partly degenerate samples or to unrepresentative ones in cases where a SRCT is a heterologous component of another nosological entity. Lymphoma, neuroblastoma, nephroblastoma, Ewing's tumour/primitive neuroendocrine tumours and rhabdomyosarcoma are discussed in detail, while other less common SRCTs are mentioned as differential diagnoses when appropriate. The use of cytogenetic and molecular techniques for differentiating between certain SRCTs is helpful in some doubtful cases. However, there are still problems in the use of these techniques, especially their cost which may delay their being introduced in every cytopathology laboratory. [source] Immature cortical responses to auditory stimuli in specific language impairment: evidence from ERPs to rapid tone sequencesDEVELOPMENTAL SCIENCE, Issue 4 2004D.V.M. Bishop Event-related potentials (ERPs) to tone pairs and single tones were measured for 16 participants with specific language impairment (SLI) and 16 age-matched controls aged from 10 to 19 years. The tone pairs were separated by an inter-stimulus interval (ISI) of 20, 50 or 150 ms. The intraclass correlation (ICC) was computed for each participant between the ERP to a single tone and the ERP to the tone pair. A high ICC indicates that the brain response to a tone pair is similar to that for a single tone. ICCs were significantly higher at short than at long ISIs. At 50-ms ISI, ICCs were higher for younger than older participants. Age and ISI interacted with SLI status: ERPs of older participants with SLI differed from age-matched controls, and resembled ERPs of younger controls, consistent with a theory of immature auditory processing in SLI. [source] Differentiating reactive mesothelial cells from metastatic adenocarcinoma in serous effusions: The utility of immunocytochemical panel in the differential diagnosis,DIAGNOSTIC CYTOPATHOLOGY, Issue 5 2009F.I.A.C., Husain A. Saleh M.D., M.B.A. Abstract Differentiating reactive mesothelial cells (RMs) from metastatic adenocarcinoma cells (MAC) in serous fluids based on cytomorphologic features alone can be very challenging. Various immunocytochemical (ICC) markers have been used to maximize the diagnostic accuracy, however, cytopathologists still encounter difficulties in effusion cytologic diagnosis. The aim of this study was to evaluate previous and recent ICC stains to identify the most sensitive and specific markers and the best panel for differentiating RM from MAC. Cell block sections from 41 MAC and 43 RM effusions cases were subjected to ICC staining for MOC-31, BerEp4, carcinoembryonic antigen (CEA), calretinin, HBME-1, CK5/6, and D2-40. For the MAC cases, the sensitivity of BerEp4, MOC-31, and CEA was 82.9, 92.6, and 17%, respectively, and the specificity was 95.3, 93, and 100%, respectively. For the RM cases, the sensitivity of calretinin, CK5/6, D2-40, and HBME-1 was 95.3, 27.9, 58.1, and 93%, respectively, and the specificity was 70.7, 73.1, 75.6, and 82.9%, respectively. The results show that BerEp4 and MOC-31 are highly sensitive and specific for detecting MAC, whereas calretinin and HBME1 are highly sensitive but only modestly specific for detecting RM cases (P < 0.05). Forced entry logistic regression revealed that using MOC-31, BerEp4, HBME-1, and calretinin, is an excellent panel for making correct diagnosis with 97.6% sensitivity in detecting MAC and 90.7% specificity in detecting RM. We conclude that adding a panel of MOC-31, BerEp4, calretinin, and HBME-1 immunostains to routine cytomorphologic features can greatly enhance the diagnostic accuracy of serous effusions. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Utility of the thromboplastin-plasma cell-block technique for fine-needle aspiration and serous effusionsDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2009D.M.L.T., Manisha B. Kulkarni M.Sc. Abstract (I) To assess the feasibility of thromboplastin-plasma (TP) method for cell block, (II) to concentrate the minimal cellular material from effusions and needle-rinses by block preparation and improve visual details, (III) to compare conventional cytological smears with cell blocks for final assessment, and (IV) to assess utility of immunocytochemistry (ICC) for diagnostic accuracy. Seventy cell blocks were prepared by TP technique using surplus fluid from 38 serous effusions, and for 32 ultrasonography-guided fine-needle aspiration cytology (FNAC) material, rinses of syringes and needles were collected in normal saline after conventional cytological smears. Then, cell blocks were compared with conventional smears for adequacy, morphologic preservation, and ICC. Absolute concordance seen in 66 cases (94%) between the smears and cell blocks. Advantages with the blocks were cellular concentration in a limited field and better cellular preservation with architectural pattern. Quality of ICC was comparable to that of standard controls. Diagnostic discrepancy was seen in two cases where cell blocks were positive but smears were negative. Two cell blocks were nonrepresentative. Cell block serves as a useful adjunct to traditional cytological smears. TP method is simple, cost effective, and reproducible. It is easy when compared with agar-embedding technique. Ancillary techniques like ICC can be performed successfully. Diagn. Cytopathol. 2009. © 2008 Wiley-Liss, Inc. [source] Secretory activity in medullary thyroid carcinoma: A cytomorphological and immunocytochemical studyDIAGNOSTIC CYTOPATHOLOGY, Issue 6 2007D.Sc., Dilip K. Das M.B.B.S., F.R.C.Path., Ph.D. Abstract Medullary thyroid carcinoma (MTC) is a relatively rare thyroid malignancy of C-cell origin that secretes calcitonin. Although its varied cytomorphologic features are well described in literature, very little is mentioned about the morphologic manifestation of its secretory activity. This study, based on nine fine needle aspiration (FNA) samples from eight MTC patients, is an attempt to present the varied cytomorphologic features suggesting secretory activity in MTC as observed in Papanicolaou and MGG stained FNA smears and correlate them with the immunocytochemical (ICC) staining for calcitonin performed on FNA smears and the serum calcitonin values. The average number of cells in these nine samples was as follows: oval/triangular/plasmacytoid (56.7%), small round (23.6%), spindle-shaped (12.7%), and miscellaneous (7.1%). The cytomorphological features suggesting secretory activity, viz., fine cytoplasmic vacuoles, azurophillic granules, marginal vacuoles, and intracytoplasmic lumina (ICL) with secretions were present in eight, eight, five, and six samples, respectively. Material likely to be amyloid, based on morphological features, was present extracellularly in three samples and both intracellularly and extracellularly in six samples. Immunocytochemically, all the nine samples stained for calcitonin and all the three stained for chromogranin showed positive cytoplasmic reaction in the neoplstic cells. The background amyloid (in six samples), the coarse cytoplasmic granules (in two samples), and the contents of ICL (in one sample) were found to be positively stained for calcitonin. The intracytoplasmic secretory material appeared to be diffusing out of some cells both in the routine MGG stained smears and in the smears stained for calcitonin. Histopathology reports of seven samples in six patients confirmed the cytodiagnosis of MTC in all. Baseline serum calcitonin values in three cases and postoperative serum calcitonin levels during follow-up in three others were high. Thus, our study highlighted the morphological manifestations of secretory activity in MTC and the nature of secretory material as calcitonin, supported by immunocytochemical staining and serum calcitonin level. Diagn. Cytopathol. 2007;35:329,337. © 2007 Wiley-Liss, Inc. [source] Detection of tumor cells in body cavity fluids by flow cytometric and immunocytochemical analysisDIAGNOSTIC CYTOPATHOLOGY, Issue 8 2006Awtar Krishan Ph.D. Abstract Measurement of electronic volume versus DNA content of nuclei can be used to discriminate between normal and malignant cells. Epithelial membrane antigen immunocytochemistry (EMA-ICC), a helpful ancillary test in body cavity fluids, is not universally accurate for detecting malignancy in effusions. The current study was undertaken to determine if multiparametric flow cytometry (based on simultaneous analysis of light scatter, nuclear volume, DNA, and nuclear protein content) in combination with (EMA-ICC) could be used for the detection of malignant cells in peritoneal and pleural fluids. We studied 130 body cavity fluids (68 peritoneal and 62 pleural fluids) by conventional cytology and multiparametric laser flow cytometry. EMA-ICC was performed using EMA antibodies and L-SAB detection system (DakoCytomation, Carpinteria, CA). EMA-ICC had significantly higher sensitivity than conventional cytology (79% versus 59%, P = 0.016) and ploidy (79% versus 38%, P = 0.001). Cytology had significantly higher specificity than ploidy (97% versus 82%, P = 0.012). The differences in specificity between EMA-ICC and ploidy (87% versus 82%, P= 0.607) or EMA-ICC and cytology (87% versus 97%, P = 0.109) were not statistically significant. However, assuming serial testing, sensitivity increased significantly for the combinations of cytology and EMA-ICC (79.4%, P = 0.016) and cytology and ploidy (73.5%, P = 0.004) as compared to cytology alone (58.8%). Also, the combination of cytology and ploidy had a higher sensitivity than ploidy alone (73% versus 38%, P < 0.0001). However, the sensitivity associated with the three tests used in serial (85.3%) was not significantly different from the sensitivities corresponding to the combination of cytology and EMA-ICC (79%) or cytology and ploidy (73%). Multiparametric flow cytometry utilizing high resolution DNA, nuclear volume, protein measurement, and ICC, in combination with cytomorphology, may be a valuable tool for rapid identification of malignant cells in body cavity fluids. Diagn. Cytopathol. 2006;34:528,541. © 2006 Wiley-Liss, Inc. [source] Comparison of three cytologic preparation methods and immunocytochemistries to distinguish adenocarcinoma cells from reactive mesothelial cells in serous effusionDIAGNOSTIC CYTOPATHOLOGY, Issue 1 2006(I.A.C.), Junko Ueda Ph.D. Abstract We assessed whether a panel of seven antibodies is useful in the differentiation of adenocarcinoma cells (ACCs) from reactive mesothelial cells (RMCs) in effusion samples and to determine optimal specimen preparation conditions for immunocytochemical analysis of effusion samples. Immunocytochemistry (ICC) was performed on three types of effusion preparations from the same effusion specimens: ethanol-fixed smears, ethanol-fixed cell -blocks, and formalin-fixed cell-blocks. Commercially available antibodies MOC-31, Ber-EP4, CA19-9, CEA, EMA, CA125, and HBME-1 were tested on RMCs from four samples of various etiology and 15 samples of adenocarcinoma from various primary sites. Ethanol-fixed smears showed strong immunoreactivity to all antibodies tested. The immunoreactivity of ethanol-fixed and formalin-fixed cell-blocks was significantly lower with all antibodies except CA19-9. Smear preparations are more sensitive than cell-blocks for immunocytochemical study. A panel of antibodies MOC-31, Ber-EP4, CA19-9, and CEA appears to be suitable to distinguish between ACCs and RMCs. Diagn. Cytopathol. 2006;34:6,10. © 2005 Wiley-Liss, Inc. [source] Desmoplastic round cell tumor of childhood: Can cytology with immunocytochemistry serve as an alternative for tissue diagnosis?DIAGNOSTIC CYTOPATHOLOGY, Issue 6 2005Dr Brijal Dave M.D. Abstract There are limited reports on the cytology of desmoplastic small round cell tumors (DSRCT). Fine needle aspiration biopsy (FNAB) findings in seven aspirates from four cases of histologically and immunohistochemically confirmed cases were analyzed with the main intention of ascertaining if cytological diagnosis of DSRCT is possible. Also assessed were the immunocytochemistry(ICC) findings in these cases. The basic cytological impression was that of a cohesive small round cell tumor. Nuclei showed granular chromatin with grooves, nuclear molding and inconspicuous nucleoli. Stromal fragments were noted in all four cases. In two cases, awareness of cytological features in the appropriate clinical context led to a suggestion of the diagnosis of DSRCT on cytology itself. ICC on destained smears showed positivity for cytokeratin, epithelial membrane antigen (EMA), desmin and WT-1 in two cases. In conclusion, given the right clinical setting, a cytological diagnosis of DSRCT is plausible and in conjunction with ICC may help in documenting the polyphenotypic nature and thereby confirming the diagnosis. Diagn. Cytopathol. 2005;32:330,335. © 2005 Wiley-Liss, Inc. [source] Role of immunocytochemistry and DNA flow cytometry in the fine-needle aspiration diagnosis of malignant small round-cell tumorsDIAGNOSTIC CYTOPATHOLOGY, Issue 4 2001Urmil Brahmi M.Sc. Abstract In the present study, DNA flow cytometry (FCM) and immunocytochemistry (ICC) with a selected panel of antibodies were performed on 51 cases of malignant tumors which were referred for fine-needle aspiration biopsy (FNAB) to our Department of Cytology for the last 2 yr. Twelve cases were diagnosed as neuroblastoma, 16 as Ewing's sarcoma, 2 as retinoblastoma, 5 as non-Hodgkin's lymphoma (NHL), 5 as rhabdomyosarcoma, 2 as peripheral neuroectodermal tumors (PNETs), and 8 as Wilms' tumor. Eleven of 12 neuroblastomas were diploid by FCM, and 1 was aneuploid, with an S-phase fraction (SPF) of 8.3%. Neuron-specific enolase (NSE) was negative in 3 and positive in 8 cases of neuroblastoma, whereas neuroblastoma marker was positive in 3/11. Sixteen of 17 Ewing's sarcomas were diploid, and 1 showed tetraploid aneuploidy, with an SPF of 10.06%. Eight of 13 Ewing's sarcomas were positive for Mic-2 gene product (Ewing's marker). All 5 NHL were positive for leukocyte-common antigen (LCA). Three of 5 rhabdomyosarcomas were diploid, and 2 cases showed aneuploidy. Rhabdomyosarcoma showed muscle-specific actin positivity in 4 and desmin positivity in 3 cases. All 3 cases of PNET were diploid and positive for the Mic-2 gene product, whereas NSE and vimentin were positive in 2 cases. Both cases of retinoblastoma were diploid. Immunostaining was noncontributory in 1 case, and the other showed positivity for the retinoblastoma gene product, NSE, and chromogranin. Seven of 8 Wilms' tumors were diploid, and 1 showed aneuploid, with an SPF of 11.13%. Seven of 8 Wilms' tumors were positive for cytokeratin (CK), 5 were positive for NSE, 6 were positive for epithelial membrane antigen (EMA), and 5 were positive for vimentin. FNAB diagnosis of malignant round-cell tumors is difficult only by light microscopy. Due to the availability of specific markers for subgrouping tumors, ICC has proved to be more useful these days, while DNA FCM has little diagnostic value, as most of them are diploid. Further ancillary studies, e.g., electron microscopy, image analysis, and other molecular investigations, are required to further categorize these tumors more precisely for better clinical management of these cases. Diagn. Cytopathol. 24:233,239, 2001. © 2001 Wiley-Liss, Inc. [source] Reproducibility, validity, and responsiveness of a disease-specific symptom questionnaire for gastroesophageal reflux diseaseDISEASES OF THE ESOPHAGUS, Issue 4 2000C. J. Allen The purpose of this study was to establish the reproducibility, validity, and responsiveness of a symptom questionnaire to assess patients with gastroesophageal reflux disease (GERD). A total of 300 patients with GERD completed questionnaires before and 6 months after laparoscopic Nissen fundoplication. Forty-six GERD patients who continued on omeprazole served as controls. Lower esophageal sphincter pressure, 24-h pH, and quality of life (SF36) were measured at baseline and follow-up. Reproducibility was calculated as an intraclass correlation coefficient (ICC) from a repeated-measures analysis of variance on symptom scores (SS) on two consecutive days. Validity was established by correlating SS with 24-h pH and SF36 scores. Responsiveness was calculated as the the ratio of the mean paired difference in score in the surgical group to the within-subject variability in control subjects. Reproducibility was very high, as revealed by an ICC of 0.92. Strong correlations between SS and SF36 scores at baseline and after surgery demonstrated high cross-sectional validity. Correlation between change in SS and change in pH, SF36 pain, general health, and physical health scores demonstrated longitudinal validity. The mean (95% confidence interval) paired differences in SS were 25.6 (23.7, 27.5) in the study and 2.0 (,3.2, 7.3) in the control groups, and the responsive index was 1.0. The estimated minimally important clinical difference was 7. We conclude that the symptom score is a reproducible, valid, and responsive instrument for assessing symptoms caused by GERD. [source] Association between tobacco control policies and smoking behaviour among adolescents in 29 European countriesADDICTION, Issue 11 2009Anne Hublet ABSTRACT Aims To investigate the associations between well-known, cost-effective tobacco control policies at country level and smoking prevalence among 15-year-old adolescents. Design Multi-level modelling based on the 2005,06 Health Behaviour in School-aged Children Study, a cross-national study at individual level, and with country-level variables from the Tobacco Control Scale and published country-level databases. Setting Twenty-nine European countries. Participants A total of 25 599 boys and 26 509 girls. Main outcome measures Self-reported regular smoking defined as at least weekly smoking, including daily smoking (dichotomous). Findings Interaction effects between gender and smoking policies were identified, therefore boys and girls were analysed separately. Large cross-national differences in smoking prevalence were documented. Intraclass correlations (ICC) of 0.038 (boys) and 0.035 (girls) were found. In the final multi-level model for boys, besides the significance of the individual variables such as family affluence, country-level affluence and the legality of vending machines were related significantly to regular smoking [b(country affluence) = ,0.010; b(partial restriction vending machines) = ,0.366, P < 0.05]. Price policy was of borderline significance [b(price policy) = ,0.026, P = 0.050]. All relationships were in the expected direction. The model fit is not as good for girls; only the legality of vending machines had a borderline significance in the final model [b(total ban vending machines) = ,0.372, P = 0.06]. Conclusions For boys, some of the currently recommended tobacco control policies may help to reduce smoking prevalence. However, the model is less suitable for girls, indicating gender differences in the potential efficacy of smoking policies. Future research should address this issue. [source] Interstitial cells of Cajal (ICC) in equine colic: an immunohistochemical study of horses with obstructive disorders of the small and large intestinesEQUINE VETERINARY JOURNAL, Issue 6 2004C. FINTL Summary Reasons for performing study: The gastrointestinal pacemaker cells, the interstitial cells of Cajal (ICC), have been implicated in several human gastrointestinal dysmotility syndromes. Recently, the involvement of these cells in equine gastrointestinal diseases has been investigated in cases of equine grass sickness where a significant reduction in ICC density was observed. Objective: To investigate ICC density in equine obstructive gastrointestinal disorders using immunohistochemical labelling methods. Methods: Intestinal samples were analysed from 44 horses undergoing exploratory surgery for colic and from 11 control animals subjected to euthanasia for conditions not related to the gastrointestinal tract. Immunohistochemical labelling of ICC was carried out using an anti-c-Kit antibody. Two independent observers assessed ICC density using a semiquantitative grading system. Results: There was a significant reduction in ICC density in horses with large colon disorders compared to the controls (P<0.01). Horses with strangulating lesions of the small intestine showed no difference when compared to the controls. Conclusions: There was a reduction in ICC density in horses with large intestinal disorders. Potential relevance: The reduction in ICC density may be associated with the clinical findings as well as recurrent colic episodes observed in a number of these cases. This immunohistochemical study provides a basis for future functional electrophysiological investigations to determine the precise effect of ICC reduction on equine intestinal motility. [source] Mapping responses to frequency sweeps and tones in the inferior colliculus of house miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2003Steffen R. Hage Abstract In auditory maps of the primary auditory cortex, neural response properties are arranged in a systematic way over the cortical surface. As in the visual system, such maps may play a critical role in the representation of sounds for perception and cognition. By recording from single neurons in the central nucleus of the inferior colliculus (ICC) of the mouse, we present the first evidence for spatial organizations of parameters of frequency sweeps (sweep speed, upward/downward sweep direction) and of whole-field tone response patterns together with a map of frequency tuning curve shape. The maps of sweep speed, tone response patterns and tuning curve shape are concentrically arranged on frequency band laminae of the ICC with the representation of slow speeds, build up response types and sharp tuning mainly in the centre of a lamina, and all (including high) speeds, phasic response types and broad tuning mainly in the periphery. Representation of sweep direction shows preferences for upward sweeps medially and laterally and downward sweeps mainly centrally in the ICC (either striped or concentric map). These maps are compatible with the idea of a gradient of decreasing inhibition from the centre to the periphery of the ICC and by gradients of intrinsic neuronal properties (onset or sustained responding). The maps in the inferior colliculus compare favourably with corresponding maps in the primary auditory cortex, and we show how the maps of sweep speed and direction selectivity of the primary auditory cortex could be derived from the here-found maps of the inferior colliculus. [source] The International Criminal Court: Reforming the Politics of International JusticeGOVERNMENT AND OPPOSITION, Issue 1 2003Spyros Economides The International Criminal Court (ICC) came into effect on 1 July 2002. This article gives an account of the historical background to the ICC and an overview of the Court's Statute, remit and powers. It is argued that the ICC is a highly politicized legal institution which will only be effective through inter-state cooperation. Despite its lengthy historical antecedents and legal precedents, prudence suggests that , due to the nature of international politics , the establishment of the ICC should be viewed as the beginning of a cumulative process of reforming the politics of international justice rather than the end of a process of transformation in international law. [source] Reliability and construct validity of the compatible MRI scoring system for evaluation of elbows in haemophilic childrenHAEMOPHILIA, Issue 2 2008A. S. DORIA Summary., We assessed the reliability and construct validity of the Compatible MRI scale for evaluation of elbows, and compared the diagnostic performance of MRI and radiographs for assessment of these joints. Twenty-nine MR examinations of elbows from 27 boys with haemophilia A and B [age range, 5,17 years (mean, 11.5)] were independently read by four blinded radiologists on two occasions. Three centres participated in the study: (Toronto, n = 24 examinations; Atlanta, n = 3; Cuiaba, n = 2). The number of previous joint bleeds and severity of haemophilia were reference standard measures. The inter-reader reliability of MRI scores was substantial (ICC = 0.73) for the additive (A)-scale and excellent (ICC = 0.83) for the progressive (P)-scale. The intrareader reliability was excellent for both P-scores (ICC = 0.91) and A-scores (ICC = 0.93). The total P- and A-scores correlated poorly (r = 0.36) or moderately (r = 0.54), but positively, with clinical-laboratory measurements. The total MRI scores demonstrated high accuracy for discrimination of presence or absence of arthropathy [P-scale, area-under-the-curve (AUC) = 0.94 ± 0.05; A-scale, AUC = 0.89 ± 0.06], as did the soft tissue scores of both scales (P-scale, AUC = 0.90 ± 0.06; A-scale, AUC = 0.86 ± 0.06). Areas-under-the-curve used to discriminate severe disease demonstrated high accuracy for both P-MRI scores (AUC = 0.83 ± 0.09) and A-MRI scores (AUC = 0.87 ± 0.09), but non-diagnostic ability to discriminate mild disease. Similar results were noted for radiographic scales. In conclusion, both MRI scales demonstrated substantial to excellent reliability and accuracy for discrimination of presence/absence of arthropathy, and severe/non-severe disease, but poor to moderate convergent validity for total scores and non-diagnostic discriminant validity for mild/non-mild disease. Compared with radiographic scores, MRI scales did not perform better for discrimination of severity of arthropathy. [source] A view from the bridge: agreement between the SF-6D utility algorithm and the Health Utilities IndexHEALTH ECONOMICS, Issue 11 2003Bernie J. O'Brien Abstract Background: The SF-6D is a new health state classification and utility scoring system based on 6 dimensions (,6D') of the Short Form 36, and permits a "bridging" transformation between SF-36 responses and utilities. The Health Utilities Index, mark 3 (HUI3) is a valid and reliable multi-attribute health utility scale that is widely used. We assessed within-subject agreement between SF-6D utilities and those from HUI3. Methods: Patients at increased risk of sudden cardiac death and participating in a randomized trial of implantable defibrillator therapy completed both instruments at baseline. Score distributions were inspected by scatterplot and histogram and mean score differences compared by paired t -test. Pearson correlation was computed between instrument scores and also between dimension scores within instruments. Between-instrument agreement was by intra-class correlation coefficient (ICC). Results: SF-6D and HUI3 forms were available from 246 patients. Mean scores for HUI3 and SF-6D were 0.61 (95% CI 0.60,0.63) and 0.58 (95% CI 0.54,0.62) respectively; a difference of 0.03 (p<0.03). Score intervals for HUI3 and SF-6D were (-0.21 to 1.0) and (0.30,0.95). Correlation between the instrument scores was 0.58 (95% CI 0.48,0.68) and agreement by ICC was 0.42 (95% CI 0.31,0.52). Correlations between dimensions of SF-6D were higher than for HUI3. Conclusions: Our study casts doubt on the whether utilities and QALYs estimated via SF-6D are comparable with those from HUI3. Utility differences may be due to differences in underlying concepts of health being measured, or different measurement approaches, or both. No gold standard exists for utility measurement and the SF-6D is a valuable addition that permits SF-36 data to be transformed into utilities to estimate QALYs. The challenge is developing a better understanding as to why these classification-based utility instruments differ so markedly in their distributions and point estimates of derived utilities. Copyright © 2003 John Wiley & Sons, Ltd. [source] Epidemiology, risk factors, and pathogenesis of cholangiocarcinomaHPB, Issue 2 2008S. A. KHAN Abstract Cholangiocarcinoma (CCA) is a fatal cancer of the biliary epithelium, arising either within the liver (intrahepatic, ICC) or in the extrahepatic bile ducts (extrahepatic ECC). Globally, CCA is the second most common primary hepatic malignancy. Several recent epidemiological studies have shown that the incidence and mortality rates of ICC are increasing. This review of the literature on the international epidemiological rates of CCA, both intra- and extrahepatic, explores possible explanations for the trends found. The possible role of epidemiological artifact in the findings is discussed and the known risk factors for CCA are summarized. These include primary sclerosing cholangitis, liver fluke infestation, congenital fibropolycystic liver, bile duct adenomas, and biliary papillomatosis, hepatolithiasis, chemical carcinogens such as nitrosamines, Thorotrast, chronic viral hepatitis, cirrhosis, chronic non-alcoholic liver disease and obesity. Potential pathways involved in the molecular pathogenesis of CCA are also summarized. [source] Validity, reliability, and responsiveness of the EQ-5D in inflammatory bowel disease in GermanyINFLAMMATORY BOWEL DISEASES, Issue 1 2010Renee G. Stark MD Abstract Background: The EuroQol (EQ)-5D questionnaire is a generic instrument measuring health-related quality of life. Its validity, reliability, and responsiveness were assessed in a large sample of Crohn's disease (CD) and ulcerative colitis (UC) patients. Methods: The EQ-5D was completed initially (270 CD and 232 UC subjects) and after 4 weeks (447 subjects) with a transition question rating health change. Responsiveness of EQ visual analog scale (EQ-VAS) and the United Kingdom (UK-index) and German EQ-5D index (EQ-index) scores to reported changes in health was evaluated by standardized response means (SRM) and meaningful differences (MDs). Results: EQ-VAS and EQ-index scores correlated well with disease activity indices and differed significantly between active disease and remission groups. All scores were reliable in test,retest (ICC: EQ-VAS: 0.89; UK-index: 0.76; German EQ-index: 0.72). According to SRM, EQ-VAS was more responsive for deterioration in health than for improvement in health and was more responsive than index scores. Index scores were most responsive for deterioration in health in subjects in remission and for improved health in subjects with active disease. MDs for improved health (EQ-VAS: 10.9; UK EQ-index: 0.076; German EQ-index: 0.050) and deteriorated health (EQ-VAS: ,14.4; UK EQ-index: ,0.109; German EQ-index: ,0.067) were significant, but MD of EQ-VAS also differed significantly according to disease activity. Conclusions: The EQ-5D generates valid, reliable, and responsive preference-based valuations of health in CD and UC. EQ-VAS scores were more responsive than EQ-5D index scores. Thus, small health differences that are important from the patient's perspective may not be reflected in the EQ-index. Inflamm Bowel Dis 2010 [source] Quantitive cytokine mRNA expression profiles in the colonic mucosa of patients with steroid naďve ulcerative colitis during active and quiescent diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2009Reikei Matsuda MD Abstract Background: Cytokines have validated roles in the immunopathogenesis of inflammatory bowel disease (IBD). This study was to investigate the expressions of tumor necrosis factor (TNF)-,, interleukin (IL)-6, IL-8, and IL-10 mRNAs in the colonic mucosa of patients with ulcerative colitis (UC) during active and quiescent UC. Methods: At colonoscopy, biopsies were taken from inflamed and non-inflamed mucosa of patients with steroid-naive UC (n = 15), non-IBD inflammatory colitis controls (ICC, n = 6), and non-colitis controls (NCC, n = 14). The presence of extensive mononuclear cells and neutrophils infiltrate in the lamina propria, cryptitis, and epithelial damage defined an inflammatory lesion in the mucosa. Quantitative cytokine mRNA expressions in biopsies were measured by real-time polymerase chain reaction (PCR). Results: Of 15 UC patients, 3 remitted with 5-aminosalicylate and 11 received granulocytapheresis; of these, 10 remitted. At baseline, IL-6, IL-8, TNF-,, and IL-10 mRNAs were high in inflamed mucosa compared with NCC (P < 0.01). In active UC, IL-6, IL-8 and IL-10 mRNAs were high compared with non-inflamed mucosa (P = 0.03, P = 0.03, P < 0.05, respectively). Both TNF-, mRNA (P = 0.03) and IL-6 mRNA (P = 0.04) were higher in UC compared with ICC. Even in non-inflamed mucosa, IL-8 and TNF-, mRNA expressions were high compared with NCC. Both IL-6 and IL-8 mRNAs decreased to normal levels after granulocytapheresis. Conclusions: During active UC, all 4 cytokine mRNA levels were high; only IL-6 and IL-8 mRNAs decreased to normal levels during remission. IL-8 mRNA was high even at sites of endoscopically quiescent UC during active disease. Steroid naďve patients respond well to granulocytapheresis. (Inflamm Bowel Dis 2008) [source] Human papillomavirus (HPV) genotype distribution in invasive cervical cancers in France: EDITH study ,INTERNATIONAL JOURNAL OF CANCER, Issue 2 2008Jean-Luc Prétet Abstract Invasive cervical cancer (ICC) remains a significant cause of morbidity and mortality in France. Since human papillomavirus (HPV) is the necessary cause of ICC, the aim of this study was to assess the type-specific prevalence of HPV in ICC in France in order to locally evaluate the potential benefit of an HPV 16/18 L1 virus-like particles (VLP) vaccination. A total of 516 histological specimens collected in 15 centers were analyzed. Among them, 86% had a diagnosis of squamous cell carcinoma (SCC) whereas 14% were adenocarcinomas (ADC). HPV genotyping was performed using the INNO-LiPA assay allowing the specific detection of 24 HPV genotypes both high risk (HR) and low risk (LR). The overall HPV prevalence in ICC was 97%. The most prevalent genotypes were HPV 16 (73%) and HPV 18 (19%) followed by HPV 31 (7%), 33, 68, 45, 52 and 58 (4.1,2.3%). HPV 16 and/or 18 were associated with 82% of ICC, 10% being HPV 16 and 18 coinfections. While HPV 16 was the most prevalent type in both SCC (74%) and ADC (64%), HPV 18 was by far more prevalent in ADC (37%) compared to SCC (16%; p < 0.001). Multiple infections with at least two different HR HPV genotypes were observed in 22% of ICC. Given the high HPV 16/18 prevalence and taking into account possible production of crossneutralizing antibodies against other HPV types, HPV 16/18 L1 VLP vaccination would be expected to significantly reduce the burden of ICC in France. © 2007 Wiley-Liss, Inc. [source] Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis updateINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Jennifer S. Smith Abstract Data on human papillomavirus (HPV) type distribution in invasive and pre-invasive cervical cancer is essential to predict the future impact of HPV16/18 vaccines and HPV-based screening tests. A meta-analyses of HPV type distribution in invasive cervical cancer (ICC) and high-grade squamous intraepithelial lesions (HSIL) identified a total of 14,595 and 7,094 cases, respectively. In ICC, HPV16 was the most common, and HPV18 the second most common, type in all continents. Combined HPV16/18 prevalence among ICC cases was slightly higher in Europe, North America and Australia (74,77%) than in Africa, Asia and South/Central America (65,70%). The next most common HPV types were the same in each continent, namely HPV31, 33, 35, 45, 52 and 58, although their relative importance differed somewhat by region. HPV18 was significantly more prevalent in adeno/adenosquamous carcinoma than in squamous cell carcinoma, with the reverse being true for HPV16, 31, 33, 52 and 58. Among HSIL cases, HPV16/18 prevalence was 52%. However, HPV 16, 18 and 45 were significantly under-represented, and other high-risk HPV types significantly over-represented in HSIL compared to ICC, suggesting differences in type-specific risks for progression. Data on HPV-typed ICC and HSIL cases were particularly scarce from large regions of Africa and Central Asia. © 2007 Wiley-Liss, Inc. [source] HLA-B alleles, high-risk HPV infection and risk for cervical neoplasia in southern Chinese women,INTERNATIONAL JOURNAL OF CANCER, Issue 6 2006Paul K.S. Chan Abstract A population-based study was conducted on 256 southern Chinese with cervical intraepithelial neoplasia grade III (CIN III) or invasive cervical cancer (ICC) and on 258 controls to examine the associations between HLA-B alleles, infection with high-risk human papillomaviruses (HPVs) and the development of cervical neoplasia. HLA-B15 was found to be protective for CIN III/ICC overall (pcorrected = 0.003), and for HPV52-positive CIN III/ICC (pcorrected = 0.003). A marginal protective effect of B15 was observed for HPV16-positive CIN III/ICC, but no significant associations were revealed for HPV18- or HPV58-positive cases. None of the HLA-B alleles were found to confer an increased risk for cervical neoplasia. HLA-B15 is common among Asian for whom HPV52, a worldwide uncommon HPV type, also exists in a relatively high prevalence. It would also be worthwhile to assess the association between HLA-B15, HPV52 and cervical cancer in other Asian populations. © 2005 Wiley-Liss, Inc. [source] Infrequent microsatellite instability in liver fluke infection-associated intrahepatic cholangiocarcinomas from ThailandINTERNATIONAL JOURNAL OF CANCER, Issue 3 2003Upama Liengswangwong Abstract The liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. The molecular basis of this ICC is poorly understood. To address possible roles of the DNA mismatch repair (MMR) system in ICC carcinogenesis, a fluorescence-labeling PCR/laser scanning technique with high sensitivity was employed to analyze genomic instability in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in 24 fresh and 13 formalin-fixed, paraffin-embedded tissues of ICC and their corresponding normal parts. Microsatellite instability (MSI) was assessed in nDNA, using 12 highly polymorphic loci including 5 Bethesda markers. These loci were mainly related to major MMR genes, hMSH2 and hMLH1. Also 3 (C)n and/or (C)n(A)n repeat instability at 1 noncoding region in the displacement-loop (D-loop) and 2 coding sequences in NADH dehydrogenase subunit 1 and subunit 5 gene in mtDNA were analyzed. MSI was only detected in 1 (2.7%), 6 (16.7%), 1 (2.9%), 1 (2.9%) or 2 (6.3%) out of 37, 36, 35, 35 or 32 cases at BAT-25, D2S123, D3S1611, D11S904 or D17S250, respectively. LOH was found at D3S1298, D3S1561, D5S346 and TP53 in 4 (18.2%) out of 22, 2 (18.2%) out of 11, 6 (33.3%) out of 18 and 3 (12.5%) out of 24 informative cases, respectively. In mtDNA, none except a single case out of the 37 (2.7%) exhibited repeat sequence instability in the D-loop. We conclude that the liver fluke infection-associated ICC in Thailand is classified as low frequency MSI or microsatellite stable type and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis. © 2003 Wiley-Liss, Inc. [source] Ethics and Foreign Policy: Structured Debates for the International Studies ClassroomINTERNATIONAL STUDIES PERSPECTIVES, Issue 2 2004Jeffrey S. Lantis Debates about humanitarian intervention, foreign and defense policy priorities, and the ethics of the use of force have become highly politicized in the post-Cold War era. This article explores the value of structured classroom debates on ethical dimensions of international relations as active teaching and learning tools for introductory and advanced international studies courses. Specifically, this article presents design information for structured debates on the ethics of the use of military force, humanitarian interventions, and U.S. foreign policy toward international institutions such as the International Criminal Court (ICC). Building on the literature on active teaching and learning, the article describes the development of these exercises and assesses their effectiveness through ten years of classroom application. [source] Tests of Muscle Strength and Physical Function: Reliability and Discrimination of Performance in Younger and Older Men and Older Men with Mobility LimitationsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2008Nathan K. LeBrasseur PT OBJECTIVES: To compare the reliability of muscle strength and physical function measures in younger and older men. DESIGN: Cross-sectional. SETTING: Academic research center. PARTICIPANTS: Thirty younger men, 31 older men, and 39 older men with mobility limitations. MEASUREMENTS: Test,retest measures of one repetition maximum (1 RM), unloaded and loaded 50-m walk and stair climb, and a lift-and-lower task. Reliability was assessed using intraclass correlation (ICC) analysis and the Bland-Altman method. RESULTS: Leg and chest press 1 RM measures identified significant differences between the groups, exhibited excellent test,retest reliability in younger men, older men, and older men with mobility limitations (ICCs=0.946,0.994) and minimal bias between Trials 1 and 2 (Bland-Altman=improvement of 21.1 and 1.1 N for leg and chest press, respectively). Test,retest measures of the time to walk 50 m and climb 12 steps also demonstrated excellent agreement (ICCs=0.980,0.988 and 0.942,992, respectively) and minimal bias (Bland-Altman=0.755,1.007 and 0.141,0.361 seconds faster, respectively). When a subject repeated these measures carrying a modest load, ICCs remained greater than 0.940, bias was similar, and the tests better discriminated between the groups. The lift-and-lower measure demonstrated excellent agreement (ICCs=0.925,0.947) and minimal bias (1.4,2.9 more shelves) and revealed significant differences between groups. CONCLUSION: Measures of muscle strength and physical function can be performed in younger men, older men, and older men with mobility limitations with high reliability. In future clinical trials, more-challenging measures of performance may better discriminate between higher-functioning study participants. [source] TELOCYTES , a case of serendipity: the winding way from Interstitial Cells of Cajal (ICC), via Interstitial Cajal-Like Cells (ICLC) to TELOCYTESJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2010L. M. Popescu Abstract Ramon y Cajal discovered a particular cell type in the gut, which he named ,interstitial neurons' more that 100 years ago. In the early 1970s, electron microscopy/electron microscope (EM) studies showed that indeed a special interstitial cell type corresponding to the cells discovered by Cajal is localized in the gut muscle coat, but it became obvious that they were not neurons. Consequently, they were renamed ,interstitial cells of Cajal' (ICC) and considered to be pace-makers for gut motility. For the past 10 years many groups were interested in whether or not ICC are present outside the gastrointestinal tract, and indeed, peculiar interstitial cells were found in: upper and lower urinary tracts, blood vessels, pancreas, male and female reproductive tracts, mammary gland, placenta, and, recently, in the heart as well as in the gut. Such cells, now mostly known as interstitial Cajal-like cells (ICLC), were given different and confusing names. Moreover, ICLC are only apparently similar to canonical ICC. In fact, EM and cell cultures revealed very particular features of ICLC, which unequivocally distinguishes them from ICC and all other interstitial cells: the presence of 2,5 cell body prolongations that are very thin (less than 0.2 ,m, under resolving power of light microscopy), extremely long (tens to hundreds of ,m), with a moniliform aspect (many dilations along), as well as caveolae. Given the unique dimensions of these prolongations (very long and very thin) and to avoid further confusion with other interstitial cell types (e.g. fibroblast, fibrocyte, fibroblast-like cells, mesenchymal cells), we are proposing the term TELOCYTES for them, and TELOPODES for their prolongations, by using the Greek affix ,telos'. [source] Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channelJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5a 2008Yaohui Zhu Abstract Nitrergic nerves are structurally and functionally associated with ICC. To further understand mechanisms of communication, the hypothesis was investigated that NO might affect large conductance K channels. To that end, we searched for IbTX-sensitive currents in ICC obtained through explant cultures from the mouse small intestine and studied effects of the NOS inhibitor omega N-nitro-L-arginine (LNNA) and the NO donor sodium nitroprusside (SNP). IbTX-sensitive currents acquired in the whole-cell configuration through nystatin perforated patches exhibited high noise levels but relatively low amplitude, whereas currents obtained in the conventional whole-cell configuration exhibited less noise and higher amplitudes; depolarization from ,80 to + 40 mV evoked 357 ± 159 pA current in the nystatin perforated patch configuration and 1075 ± 597 pA using the conventional whole-cell configuration. Immunohistochemistry showed that ICC associated with ganglia and Auerbach's plexus nerve fibers were immunoreactive to BK antibodies. The IbTX-sensitive currents were increased by SNP and inhibited by LNNA. BK blockers suppressed spontaneous transit outward currents in ICC. After block of BK currents, or before these currents became prominent, calcium currents were activated by depolarization in the same cells. Their peak amplitude occurred at ,25 mV and the currents were increased with increasing extracellular calcium and inhibited by cobalt. The hypothesis is warranted that nitrergic innervation inhibits ICC excitability in part through activation of BK channels. In addition, NO is an intracellular regulator of ICC excitability. [source] Interstitial Cajal-like cells in rat mesentery: an ultrastructural and immunohistochemical approachJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2008M. E. Hinescu Abstract Interstitial Cajal-like Cells (ICLC) were recently recognized in a plethora of non-digestive organs. Here, we describe a cell type of rat mesentery sharing ultrastructural and immunohistochemical features with ICLC. Mesenteric ICLC were demonstrated by transmission electron microscopy (TEM) and further tested by light microscope immunohistochemistry. The cell described here fulfils the TEM diagnostic criteria accepted for ICLC: location in the connective interstitium; close vicinity to nerves, capillaries and other interstitial cells; characteristic long, moniliform cell processes; specialized cell-to-cell junctions; caveolae; mitochondria at 5,10% of cytoplasmic volume; rough endoplasmic reticulum at about 1,2%; intermediate and thin filaments, microtubules; undetectable thick filaments. The processes of this mesenteric ICLC were particularly long, with a mean length of 24.91 ,m (10.27,50.83 ,m), and a convolution index of 2.32 (1.37,3.63) was calculated in order to measure their potential length. Mean distances versus main target cells of ICLC,nerve bundles, vessels, adipocytes and macrophages,were 110.69, 115.80, 205.07 and 34.65 nm, respectively. We also tested the expression of CD117/c-kit, CD34, vimentin, ,-smooth muscle actin, nestin, NK-1, tryptase and chymase and the antigenic profile of the mesenteric ICLC was comparable if not identical with that recently observed in ICLC from other extra-digestive tissues. Due to the peculiar aspect of the mesenteric ICLC processes it can be hypothesized that these cells form a three-dimensional network within the mesentery that is at the same time resistant and deformable following stretches consequent to intestine movements, mainly avoiding blood vessels closure or controlling blood vessels rheology. It remains, however, to be established if and how such cells are connected with the archetypal enteric ICC. [source] Close relation of arterial ICC-like cells to the contractile phenotype of vascular smooth muscle cellJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2007Vladimír Pucovský Abstract This work aimed to establish the lineage of cells similar to the interstitial cells of Cajal (ICC), the arterial ICC-like (AIL) cells, which have recently been described in resistance arteries, and to study their location in the artery wall. Segments of guinea-pig mesenteric arteries and single AIL cells freshly isolated from them were used. Confocal imaging of immunostained cells or segments and electron microscopy of artery segments were used to test for the presence and cellular localization of selected markers, and to localize AIL cells in intact artery segments. AIL cells were negative for PGP9.5, a neural marker, and for von Willebrand factor (vWF), an endothelial cell marker. They were positive for smooth muscle ,-actin and smooth muscle myosin heavy chain (SM-MHC), but expressed only a small amount of smoothelin, a marker of contractile smooth muscle cells (SMC), and of myosin light chain kinase (MLCK), a critical enzyme in the regulation of smooth muscle contraction. Cell isolation in the presence of latrunculin B, an actin polymerization inhibitor, did not cause the disappearance of AIL cells from cell suspension. The fluorescence of basal lamina protein collagen IV was comparable between the AIL cells and the vascular SMCs and the fluorescence of laminin was higher in AIL cells compared to vascular SMCs. Moreover, cells with thin processes were found in the tunica media of small resistance arteries using transmis-sion electron microscopy. The results suggest that AIL cells are immature or phenotypically modulated vascular SMCs constitutively present in resistance arteries. [source] About the presence of interstitial cells of Cajal outside the musculature of the gastrointestinal tractJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2005Jan D. Huizinga Santiago Ramon y Cajal observed a special cell type that appeared to function as endstructures of the intrinsic nervous system in several organs. These cells were structurally and functionally further characterized in the gut musculature and named interstitial cells of Cajal (ICC). In recent years, interstitial cells have been identified in the vasculature, urinary tract, glands and other organs. Their morphologies and functions are just beginning to be clarified. It is likely that amongst them, subtypes will be discovered that warrant the classification of interstitial cells of Cajal. This "point of view" continues the discussion on the criteria that should be used to identify ICC outside the musculature of the gut. [source] | ||||||||||||||||||||||||||||||||||||||||||||||