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Clinical Markers (clinical + marker)
Kinds of Clinical Markers Selected AbstractsBrain involvement in rheumatoid arthritis: A magnetic resonance spectroscopy studyARTHRITIS & RHEUMATISM, Issue 11 2009Bart J. Emmer Objective Tumor necrosis factor , was recently implicated as an important mediator of communication between the peripheral and cerebral immune systems in an animal model of chronic inflammation. The purpose of this study was to examine by proton magnetic resonance spectroscopy (1H-MRS) the influence of inflammation on cerebral metabolism in patients with rheumatoid arthritis (RA). Methods Single-voxel 1H-MRS of the centrum semiovale was performed on 35 RA patients (6 men and 29 women; mean ± SD age 51.8 ± 14.6 years) and 28 healthy age- and sex-matched control subjects (9 men and 19 women; mean ± SD age 50.2 ± 10.4 years). None of the study subjects had any neurologic signs or symptoms. Clinical markers of disease activity were correlated with the 1H-MRS findings. Results Patients with active RA, as reflected by an elevated erythrocyte sedimentation rate (ESR), had a significantly higher ratio of choline to creatine and a significantly lower ratio of N -acetylaspartate to choline than did patients with inactive RA, as reflected by a normal ESR. Moreover, the ratios of choline to creatine and NAA to choline were significantly correlated with the ESR after correction for age, sex, smoking status, handedness, alcohol consumption, medication use, and disease duration. Medication use had no additional effect on these associations. Conclusion Our data show that systemic inflammation in RA is associated with metabolic changes in the brain. [source] Review of animal models for autism: implication of thyroid hormoneCONGENITAL ANOMALIES, Issue 1 2006Miyuki Sadamatsu ABSTRACT,, Autism is a behaviorally defined disorder associated with characteristic impairments in social interactions and communication, as well as restricted and repetitive behaviors and interest. Its prevalence was once thought to be 2/10 000, but recently several large autism prevalence reviews revealed that the rate of occurrence was roughly 30/10 000. While it has been considered a developmental disorder, little is certain about its etiology. Neuroanatomical studies at the histological level in the brains of autistic patients provide many arguments in the etiology of autism. Results from postmortem and imaging studies have implicated many major structures of the brain including the limbic system, cerebellum, corpus callosum, basal ganglia and brainstem. There is no single biological or clinical marker for autism. While several promising candidate genes have been presented, the critical loci are yet unknown. Environmental influences such as rubella virus, valproic acid, and thalidomide exposure during pregnancy are also considered important, as concordance in monozygotic twins is less than 100% and the phenotypic expression of the disorder varies widely. It is thus hypothesized that non-genetic mechanisms contribute to the onset of autistic syndrome. In light of these ambiguities, hope is held that an animal model of autism may help elucidate matters. In this article, we overview most of the currently available animal models for autism, and propose the rat with mild and transient neonatal hypothyroidism as a novel model for autism. [source] Sub-threshold manic symptoms in recurrent major depressive disorder are a marker for poor outcomeACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2009D. J. Smith Objective:, A small but significant proportion of patients with major depressive disorder (MDD) report mild manic symptoms which are below the diagnostic threshold for a hypomanic episode. Method:, We tested for an association between sub-threshold manic symptoms and clinical outcome in almost 600 patients with recurrent MDD who also had no known family history of bipolar disorder. Results:, 9.6% of this large sample had a life-time history of sub-threshold manic symptoms. These patients were significantly more likely to have a history of poor response to antidepressants (OR 2.84; 95% CI 1.23,6.56; P < 0.02) and more likely to have experienced psychosis (OR 2.07; 95% CI 1.05,4.09; P < 0.04). They had also experienced more depressive episodes on average (P = 0.006) and were more likely to have been admitted to hospital (P < 0.03). Conclusion:, Sub-threshold manic symptoms in patients with recurrent MDD may be a useful clinical marker for poor response to antidepressants and a more morbid long-term clinical course. [source] Nationwide prevalence and prognostic significance of clinically diagnosable protein-calorie malnutrition in hospitalized inflammatory bowel disease patientsINFLAMMATORY BOWEL DISEASES, Issue 8 2008Geoffrey C. Nguyen MD Abstract Background Inflammatory bowel disease (IBD) patients are at increased risk of protein-calorie malnutrition. We sought to determine the prevalence of clinically diagnosable malnutrition among those hospitalized for IBD throughout the United States and whether this malnutrition influenced health outcomes. Methods We queried the Nationwide Inpatient Sample between 1998 and 2004 to identify admissions for Crohn's disease (CD) or ulcerative colitis (UC) and a representative sample of non-IBD discharges. We assessed the prevalence and predictors of malnutrition and its association with in-hospital mortality and resource utilization. Results The prevalence of malnutrition was greater in CD and UC patients than in non-IBD patients (6.1% and 7.2% versus 1.8%, P < 0.0001). The adjusted odds ratio for malnutrition among IBD admissions compared with non-IBD admissions was 5.57 [95% confidence interval (CI): 5.29,5.86]. More IBD discharges than non-IBD discharges with malnutrition received parenteral nutrition (26% versus 6%, P < 0.0001). There was increased likelihood of malnutrition among those with fistulizing CD (OR 1.65; 95% CI: 1.50,1.82) and among those who had undergone bowel resection (OR 1.37; 95% CI: 1.27,1.48). Malnutrition was associated with increased in-hospital mortality 3.49 (95% CI: 2.89,4.23), length of stay (11.9 days versus 5.8 days, P < 0.00001), and total charges ($45,188 versus $20,295, P < 0.0001). Conclusions Clinically apparent malnutrition is more frequent among IBD admissions than among non-IBD admissions. Its association with greater mortality and resource utilization may reflect more severe underlying disease that can lead to both malnutrition and worse outcomes. Nonetheless, diagnosable malnutrition may serve as a clinical marker of poor IBD prognosis in hospitalized patients. (Inflamm Bowel Dis 2008) [source] Circulating soluble cytochrome c in liver disease as a marker of apoptosisJOURNAL OF INTERNAL MEDICINE, Issue 2 2003Z. Ben-Ari Abstract. Ben-Ari Z, Schmilovotz-Weiss H, Belinki A, Pappo O, Sulkes J, Neuman MG, Kaganovsky E, Kfir B, Tur-Kaspa R, Klein T (Beilinson and Golda Campuses, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and In Vitro Toxicology Laboratory, Sunnybrook Women's College, Toronto, Canada) Circulating soluble cytochrome c in liver disease as a marker of apoptosis. J Intern Med 2003; 254: 168,175. Objectives. To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity. Design. Laboratory research study with comparison group. Setting. Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada. Subjects. A total of 108 patients with liver disease and 30 healthy controls. Interventions. Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme-linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick-end-labelling (TUNEL) assay. Main outcome measures. Soluble cytochrome c level by type of liver disease by clinical and histological findings. Results. Soluble cytochrome c concentration (mean 187.1 ± 219.5 ng mL,1) was significantly higher in patients with liver disease than in controls (39.8 ± 35.1 ng mL,1; P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 ± 2844.8 ng mL,1; P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 ± 297.0 ng mL,1) than the portal vein (mean 169.2 ± 143.3 ng mL,1), and it was highly detectable in bile (mean 2288.0 ±4596.0 ng mL,1) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 ±304.3 ng mL,1) than treated patients (77.9 ± 35.8 ng mL,1; P = 0.001). Conclusions. Soluble cytochrome c levels are increased in different types of liver disease. Soluble cytochrome c is probably derived from the liver and secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble cytochrome c may serve as a serum marker of apoptosis. [source] Oral candidiasis as a clinical marker related to viral load, CD4 lymphocyte count and CD4 lymphocyte percentage in HIV-infected patientsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2002J. Campo Abstract Background:, High viral load is currently considered to be one of the main indicators of the progression of HIV-induced immunodepression, but few studies have analysed its relationship to the presence of oral candidiasis (OC). The aim of this cross-sectional study is to analyse the relationship between viral load, total CD4 lymphocyte count, and percentage of CD4 lymphocytes to the occurrence of OC. Methods:, The present cross-sectional study included 156 HIV-infected patients seen at a clinic for sexually transmitted diseases and HIV. We assesed the presence or absence of OC, and microbiological samples were obtained from the palatine mucosa and dorsal tongue for a smear stained with KOH (potassium hydroxide) and culture on Sabouraud's dextrose agar in all patients. Viral load was determined by quantification of viral RNA in peripheral blood with a minimum detectable level of 500 RNA copies/ml. CD4+ counts/CD4+ percentage were categorized as <200/<14%, 200,499/14,28%, and >500/>29%, and HIV viral loads were categorized as <500, 500,10,000, >10,000 copies/ml. Results:, Thirty-eight percent (37.8%) of the patients had OC. Patients with CD4+ lymphocyte counts below 200×106/l and CD4+ percentages below 14% showed a significantly higher frequency of OC (57.9% and 48.0%, respectively). Patients with a viral load over 10,000 copies/ml also had OC more frequently (44.8%). In the multiple logistic regression analysis, OC showed a statistically significant association with high viral load [>10,000 vs <500, odds ratio (OR)=11.4], low percentage of CD4+ lymphocytes (<14% vs >28%, OR=5), and injection drug use (IDU vs heterosexual transmission, OR=10.2). In HIV-infected patients, high viral load was associated with more frequent OC, regardless of CD4+ lymphocyte level. Conclusions:, These findings suggest that oral candidiasis could be a useful clinical marker of patients with high viral load. In view of these results, emphasis should be placed on the importance of systematic examination of the oral cavity in all medical follow-up examinations of HIV-infected patients. [source] Absence of inferior labial or lingual frenula is not a useful clinical marker for Ehlers,Danlos syndrome in the UKJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2006S Shankar [source] Measuring protein excretion in pregnancyNEPHROLOGY, Issue 5 2007JANE L HOLT SUMMARY: The recognition and detection of proteinuria has been acknowledged as an important clinical marker of renal disease since 1827 when Richard Bright published his landmark medical case reports. In more recent times, the broader community of clinicians has come to share the enthusiasm of nephrologists in recognizing the importance of protein excretion, not only as a marker of current renal disease but also as a predictor of long-term renal and cardiovascular morbidity and mortality. It is important that methods for detecting and measuring proteinuria are accurate, and this is particularly relevant to diseases that are defined by the detection of proteinuria, such as pre-eclampsia. This review will first discuss current knowledge of protein handling by the normal kidney, then the changes in normal and hypertensive pregnancy, and finally, how recent advances in our understanding of proteinuria may affect our future management of hypertensive pregnancies. [source] Development of a client-generated health outcome measure for community nursingAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 5 2000Rhonda Griffiths Objective:To develop a client-generated outcome measure for use in community nursing. Method:Participants for the study were identified from the case load of community health nurses, from a nursing home service and from residents of a retirement village. All participants had a diagnosis of venous leg ulcer (VLU) and/or type 2 diabetes. Preliminary development of the measure involved focus groups of community clients and health professionals, and pilot testing of an existing quality of life (QoL) measure, the Patient-Generated Index. The resulting Client-Generated Index was tested for reliability and validity. Results:The Pearson's correlation coefficient between administration of the CGI at T1 and T2 was 0.526 (n=51; p=0.0001). The CGI correlated significantly with four of eight dimensions of the SF-36, and with pain as a clinical marker for VLU r=0.54 (p=0.001). Overall, participants with VLU reported a lower QoL (mean CGI score 2.8) compared to those with diabetes (mean CGI score 4.1). Conclusions:The CGI was developed to measure outcomes in community health settings. Some measures of its reliability and validity are demonstrated and further research is needed to validate the instrument using other client groups. Implications:If routine assessment and evaluation is to contribute to measures of outcome, the instruments need to be concise and acceptable to health care providers. The CGI has all these properties. [source] Plasma P-selectin is elevated in the first trimester in women who subsequently develop pre-eclampsiaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 7 2001P.M. Bosio Objective To report plasma concentrations of the adhesion cell molecule P-selectin during pregnancy to determine the effect of subsequent development of hypertension and pre-eclampsia. Design A longitudinal study. Methods A longitudinal study involving 70 women followed up from early pregnancy; 20 who subsequently developed pre-eclampsia were compared with 24 who developed gestational hypertension and 26 normotensive women with normal obstetric outcome. The determination of citrate plasma soluble P-selectin levels throughout pregnancy was performed using a commercial quantitative sandwich immunoassay kit. The temporal course of plasma P-selectin in the three groups of subjects was analysed. Results There was no significant difference in mean plasma P-selectin concentration between normotensive and gestational hypertensive subjects at any stage of pregnancy. Using a cutoff level of 60 ng/mL, P-selectin concentration at 10,14 weeks had a negative predictive value for pre-eclampsia of almost 99%. Mean plasma P-selectin concentrations were significantly elevated by 10,14 weeks in women who later developed pre-eclampsia (P<0.001). Conclusions Our data support an inflammatory model for pre-eclampsia whereby endothelial cell activation may be secondary to a primary inflammatory response. Plasma P-selectin has significant potential as a first trimester clinical marker of pre-eclampsia. [source] Prediction of posthepatectomy hepatic functional reserve by serum hyaluronateBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2009S. Yachida Background: Serum hyaluronate can be used as an index of hepatic sinusoidal endothelial cell function and hepatic fibrosis. This study was designed to clarify the clinical significance of the serum hyaluronate level as a parameter of functional reserve. Methods: The study included 283 patients undergoing hepatectomy. Liver function parameters were examined before surgery and compared with outcomes. Patients were retrospectively grouped according to the presence or absence of postoperative hepatic dysfunction. Results: Preoperative serum hyaluronate levels were significantly raised in parallel with the degree of severity of the underlying chronic liver disease. Regression analysis revealed serum hyaluronate level to be an independent predictor of portal hypertension. In 131 patients undergoing major hepatectomy, preoperative hyaluronate levels were significantly higher in patients with poor outcome. Multivariable logistic regression analysis demonstrated serum hyaluronate and total bilirubin levels to be independent variables associated with postoperative hepatic dysfunction. Patients with high indocyanine green retention rate at 15 min (over 15 per cent) showed significantly higher morbidity and mortality rates when their serum hyaluronate levels were over 180 ng/ml. Conclusion: Serum hyaluronate is a simple clinical marker for portal venous pressure and a reliable auxiliary parameter of hepatic functional reserve in combination with other liver function tests. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab eraCANCER SCIENCE, Issue 10 2009Ritsuko Seki We evaluated the usefulness of prognostic markers in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab (R-CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R-CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl-6), postgerminal center B cells (Multiple myeloma-1), and apoptosis (Bcl-2). The median follow-up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R-CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non-GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl-6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl-2 (P = 0.001) or MUM1 (P = 0.011), or non-GCB subtype (P = 0.05) was associated with worse overall survival. In the R-CHOP group, however, these biomarkers except Bcl-6 were not significant prognostic factors. The patients with non-GCB subtype showed improved survival in the R-CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R-CHOP group (P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re-evaluated. (Cancer Sci 2009; 100: 1842,1847) [source] Long-term study of vascular perfusion effects following arteriovenous sheathotomy for branch retinal vein occlusionACTA OPHTHALMOLOGICA, Issue 3 2010Mahiul M. K. Muqit Abstract. Purpose:, To evaluate the perfusion effects and long-term visual outcome of pars plana vitrectomy (PPV) combined with arteriovenous sheathotomy (AVS) with or without triamcinolone for nonischaemic branch retinal vein occlusion (NI-BRVO). Methods:, Prospective, interventional case series of eight patients with NI-BRVO and haemorrhagic macular oedema. Patients underwent PPV and AVS (n = 5), or PPV, AVS and intravitreal triamcinolone (IVT, n = 3). A masked grading technique assessed fundus photographs and fluorescein angiography (FFA) following surgery. Scanning laser ophthalmoscopy/optical coherence tomography (SLO/OCT) evaluated macular oedema and outer retinal architecture. Main outcomes examined included visual acuity (VA), retinal reperfusion, collateral vessel regression, vascular dilatation, cystoid macular oedema (CMO), and ocular neovascularization. Results:, Seven of eight patients underwent uncomplicated surgery, with increased intraretinal perfusion and reduced engorgement of distal retinal veins. The mean pre-logMAR VA was 0.8 (SD 0.17) and did not improve significantly after surgery (post-logMAR 0.6, SD 0.38; p = 0.11, paired t -test). SLO/OCT showed persistent CMO in four patients, and subfoveal thinning of the photoreceptor layer. Collateral vessels disappeared at the blockage site post-AVS in 7/8 eyes, and this was associated with improved retinal perfusion. Six of eight patients developed epiretinal membrane. No patients developed ocular neovascularization. The average follow-up was 34.5 months. Conclusions:, PPV with AVS is a safe procedure, and adjunctive IVT had no additional effects on vascular perfusion. Successful decompressive surgery was followed by disappearance of collateral vessels at the BRVO blockage site and was a clinical marker for intravascular reperfusion. Long-term epiretinal gliosis and subfoveal photoreceptor atrophy limited functional and visual recovery. [source] Kisspeptin serum levels in girls with central precocious pubertyCLINICAL ENDOCRINOLOGY, Issue 4 2009L. De Vries Summary Objective, Central precocious puberty (CPP) causes early epiphyseal maturation, and early initiation of treatment improves final height. Unfortunately, there is no one parameter that can distinguish CPP from premature thelarche (PT), which is self-limited and requires no therapy. In animal models, kisspeptin, the ligand for the G-protein coupled receptor GPR54, was found to induce precocious activation of the gonadotrophic axis. Data on kisspeptin levels in girls with precocious puberty or in healthy prepubertal girls are lacking. We measured blood kisspeptin levels in girls with CPP and evaluated its potential as a clinical marker for CPP. Design, This was a case,control study. Patients, Thirty-one girls clinically diagnosed with CPP and 14 prepubertal age-matched healthy controls. Measurements, Kisspeptin blood levels. Results, Kisspeptin levels were significantly higher in the girls with CPP than in the controls: 14·62 ± 10·2 pmol/l vs. 8·35 ± 2·98 pmol/l, P < 0·05. Within the CPP group, there were no significant differences between the girls with a peak LH >5·0 IU/l and those with a peak LH ,5·0 IU/l regarding kisspeptin or any of the clinical, laboratory or ultrasound parameters, or in Tanner stage. No correlation was found between kisspeptin and body mass index standard deviation score (BMI-SDS) or height-SDS (Ht-SDS) for the entire cohort, or when analysed separately for the CPP group and the control group. Conclusions, Although kisspeptin is significantly higher in girls with true CPP than in age-matched prepubertal controls, the evident overlap limits its use as a single diagnostic tool until further data obtained in larger studies should prove otherwise. [source] Recombinant hGH replacement therapy and the hypothalamus,pituitary,thyroid axis in children with GH deficiency: when should we be concerned about the occurrence of central hypothyroidism?CLINICAL ENDOCRINOLOGY, Issue 6 2003Claudia Giavoli Summary objective, Recombinant hGH treatment may alter thyroid hormone metabolism and we have recently reported that 50% of patients with GH deficiency (GHD) due to organic lesions, previously not treated with thyroxine, developed hypothyroidism during treatment with recombinant human GH (rhGH). These results prompted us to evaluate the impact of rhGH treatment on thyroid function in children with GHD. design, Open study of GH treatment up to 12 months. Investigations were performed at baseline, and after 6 and 12 months of GH therapy. measurement and study subjects, Serum TSH, FT4, FT3, AbTg and AbTPO, IGF-I, height and weight, were evaluated in 20 euthyroid children (group A) with idiopathic isolated GHD and in six children (group B) with multiple pituitary hormone deficiencies (MPHD) due to organic lesions. Among the latter, four already had central hypothyroidism and were on adequate LT4 replacement therapy, while two were euthyroid at the beginning of the study. results, Serum IGF-I levels normalized in all patients. In both groups, a significant reduction in FT4 levels (P < 0·01) occurred during rhGH therapy. No patient in group A had FT4 values into the hypothyroid range, while in four of six patients in group B, fell FT4 levels into the hypothyroid range during rhGH. In particular, the two euthyroid children developed central hypothyroidism during rhGH treatment, and their height velocities did not normalize until the achievement of euthyroidism through appropriate LT4 substitution. No variation in serum FT3 and TSH levels was recorded in either groups. conclusion, Contrary to that observed in patients with MPHD, rhGH replacement therapy does not induce central hypothyroidism in children with idiopathic isolated GHD, further supporting the view that in children with MPHD, as in adults, GHD masks the presence of central hypothyroidism. Slow growth (in spite of adequate rhGH substitution and normal IGF-I levels) is an important clinical marker of central hypothyroidism, therefore a strict monitoring of thyroid function is mandatory in treated children with MPHD. [source] Evidence that thalidomide modifies the immune response of patients suffering from actinic prurigoINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2004Iris Estrada-G PhD Background, Actinic prurigo (AP) is a photodermatosis with a restricted ethnic distribution, mainly affecting Mestizo women (mixed Indian and European). The lesions are polymorphic and include macules, papules, crusts, hyperpigmentation and lichenification. Thalidomide, an effective immunomodulatory drug, was first used successfully to treat AP in 1973. In this work we describe the effect that thalidomide had on TNF-, sera levels and on IL-4- and IFN gamma (IFN,)-producing lymphocytes of actinic prurigo (AP) patients. Methods, Actinic prurigo patients were analyzed before and after thalidomide treatment. The percentage of IL-4+ or IFN,+ CD3+ lymphocytes was analyzed in eight of them by flow cytometry. TNF, in sera was measured by ELISA in 11 patients. Results, A direct correlation was observed between resolution of AP lesions and an increase in IFN,+ CD3+ peripheral blood mononuclear cells (P , 0.001) and a decrease in TNF, serum levels (no statistical difference). No IL-4+ CD3+ cells were detected. Conclusions, Our findings confirm that AP is a disease that has an immunological component and that thalidomide clinical efficacy is exerted not only through inhibition of TNF, synthesis, but also through modulation of INF,-producing CD3+ cells. These cells could be used as clinical markers for recovery. [source] Haemolytic uraemic syndrome: prognostic factorsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2000D. A. Green Haemolytic uraemic syndrome (HUS) associated with Escherichia coli O157:H7 is the commonest cause of acute renal failure (ARF) in childhood. Production of verotoxin by the organism is pivotal in the pathogenesis of the disease. Verotoxin binds to a receptor on blood and endothelial cells, expressed as the P1 blood group antigen on red blood cells. A protective effect of the P1 phenotype has been proposed in this disease. This study investigates prognostic factors and the relationship between outcome and P1 phenotype in 27 cases of diarrhoea-associated HUS. A poor outcome as defined by the presence of chronic renal failure (CRF), hypertension or proteinuria on 6 month follow-up was associated with the age of the patient at presentation and with the following clinical markers: maximum WBC and duration of raised WBC, duration of anuria and duration of need for dialysis. None of these outcome measures or prognostic factors, and no extra-renal manifestations of the disease were associated with P1 phenotype. [source] Early Markers of Prolonged Hospital Stays in Older People: A Prospective, Multicenter Study of 908 Inpatients in French Acute HospitalsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2006Pierre-Olivier Lang MD OBJECTIVES: To identify early markers of prolonged hospital stays in older people in acute hospitals. DESIGN: A prospective, multicenter study. SETTING: Nine hospitals in France. PARTICIPANTS: One thousand three hundred six patients aged 75 and older were hospitalized through an emergency department (Sujet Âgé Fragile: Évaluation et suivi (SAFEs) ,Frail Elderly Subjects: Evaluation and follow-up). MEASUREMENTS: Data used in a logistic regression were obtained through a gerontological evaluation of inpatients, conducted in the first week of hospitalization. The center effect was considered in two models as a random and fixed effect. Two limits were used to define a prolonged hospital stay. The first was fixed at 30 days. The second was adjusted for Diagnosis Related Groups according to the French classification (f-DRG). RESULTS: Nine hundred eight of the 1,306 hospital stays that made up the cohort were analyzed. Two centers (n=298) were excluded because of a large volume of missing f-DRGs. Two-thirds of subjects in the cohort analyzed were women (64%), with a mean age of 84. One hundred thirty-eight stays (15%) lasted more than 30 days; 46 (5%) were prolonged beyond the f-DRG-adjusted limit. No sociodemographic variables seemed to influence the length of stay, regardless of the limit used. For the 30-day limit, only cognitive impairment (odds ratio (OR)=2.2, 95% confidence interval (CI)=1.2,4.0) was identified as a marker for prolongation. f-DRG adjustment revealed other clinical markers. Walking difficulties (OR=2.6, 95% CI=1.2,16.7), fall risk (OR=2.5, 95% CI=1.7,5.3), cognitive impairment (OR=7.1, 95% CI=2.3,49.9), and malnutrition risk (OR=2.5, 95% CI=1.7,19.6) were found to be early markers for prolonged stays, although dependence level and its evolution, estimated using the Katz activity of daily living (ADL) index, were not identified as risk factors. CONCLUSION: When the generally recognized parameters of frailty are taken into account, a set of simple items (walking difficulties, risk of fall, risk of malnutrition, and cognitive impairment) enables a predictive approach to the length of stay of elderly patients hospitalized under emergency circumstances. Katz ADLs were not among the early markers identified. [source] Prediction of diagnosis of immunoglobulin a nephropathy prior to renal biopsy and correlation with urinary sediment findings and prognostic gradingJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2008Kazutaka Nakayama Abstract Several clinical markers correlate well with the diagnosis and prognosis of IgA nephropathy (IgAN). In the present study, we re-evaluated the usefulness of these four clinical markers for prediction of the diagnosis of patients with IgAN through a comparison between many more patients with IgAN and those with other types of renal diseases. 364 patients with IgAN and 289 with other types of renal disease were examined. An analysis was performed prior to renal biopsy, using clinical markers including, serum IgA, serum IgA/C3 ratio, number of red blood cells in urinary sediments, and urinary protein. Patients with IgAN were divided into four groups according to histopathological findings. Presence of microscopic hematuria, persistent proteinuria, high serum IgA levels, and the serum IgA/C3 ratios are useful for prediction of diagnosis of IgAN and distinguishing it from other renal diseases. Blood pressure, urinary protein, serum uric acid, renal function, and urinary sediment findings may be useful for prediction of prognostic grading in patients with IgAN. J. Clin. Lab. Anal. 22:114,118, 2008. © 2008 Wiley-Liss, Inc. [source] Anthropometric and cephalometric measurements in X-linked hypohidrotic ectodermal dysplasiaORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 4 2007MO Lexner Structured Abstract Authors,,, Lexner MO, Bardow A, Bjorn-Jorgensen J, Hertz JM, Almer L, Kreiborg S. Objective,,, To describe the somatic development and craniofacial morphology in males affected with hypohidrotic ectodermal dysplasia (HED) and female carriers and to find clinical markers for early clinical diagnosis of possible female carriers. Design,,, A clinical and radiographic examination of the affected males and the female carriers. Setting and sample population,,, Twenty-four affected males and 43 female carriers with a known mutation in the ED1 gene were examined in a dental clinic in either Copenhagen or Aarhus, Denmark. Experimental variables,,, Height, body mass index (BMI) and head circumference. Cephalometric analysis of the craniofacial morphology. Outcome measure,,, Data on the somatic and craniofacial development in the affected males and female carriers. Results,,, No difference was observed regarding body height in the affected males and female carriers, BMI values were lower than the mean in most affected boys and adolescence and head circumference was somewhat decreased in both groups compared to normative data. The cephalometric analysis showed a reduced maxilla length and prognathism, a normal size and shape of the mandible and a reduced sagittal jaw relationship in both HED groups. Furthermore, affected males had a retroclined nasal bone and a more anteriorly inclined maxilla. A short nose, protruding lips, reduced facial convexity and facial height, characterized the soft tissue profile of the affected males. In female carriers, the lips were significantly retruded when compared with controls. Conclusion,,, No specific somatic or cephalometric markers could be observed, in the female carrier group. [source] Transforming growth factor-,1 in bronchoalveolar lavage fluid from children with cystic fibrosis,PEDIATRIC PULMONOLOGY, Issue 11 2009William T. Harris MD Abstract Rationale Transforming factor ,1 (TGF-,1) genetic polymorphisms have been identified as a modifier of cystic fibrosis (CF) lung disease severity. However, few data link TGF-,1 protein levels and clinical markers of CF lung disease severity. Objectives To determine the association between protein levels of TGF-,1 in pediatric CF bronchoalveolar lavage fluid (BALF) and clinical parameters of CF lung disease severity. Methods Total TGF-,1 was measured in BALF from 30 pediatric CF patients and 12 non-CF disease controls undergoing clinically indicated flexible bronchoscopy, and compared to four indicators of clinical disease: infection, inflammation, pulmonary function, and recent/recurrent hospitalization. Results TGF-,1 was elevated in CF BALF compared to non-CF controls (135,±,15,pg/ml vs. 57,±,10,pg/ml, P,<,0.01). In CF BALF, increased TGF-,1 was associated with elevated BALF PMN % (r,=,0.67, P,<,0.01). BALF TGF-,1 was increased in CF subjects whose FEV1 after the completion of antibiotic therapy remained below CF age-normative median values (205.9,±,20.5,pg/ml vs. 106.4,±,24.0, P,=,0.01). BALF TGF-,1 was increased in CF children hospitalized in the previous year compared to those not recently hospitalized (169.9,±,21.6,pg/ml vs. 107.5,±,17.5,pg/ml, P,=,0.04). Neither the presence of a bacterial pathogen nor bacterial quantity was associated with BALF TGF-,1. Conclusions In CF, BALF TGF-,1 is elevated compared to non-CF controls. Increased BALF TGF-,1 is associated with neutrophilic inflammation, diminished lung function and recent hospitalization. Further investigation is needed to address mechanisms behind these associations. Pediatr Pulmonol. 2009; 44:1057,1064. ©2009 Wiley-Liss, Inc. [source] Expression of Integrin Receptors on Peripheral Lymphocytes: Correlation with Endometrial Receptivity1AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2001VENKATA RAMI K. REDDY PROBLEM: To investigate the expression of integrin (ITG) cell adhesion molecules on peripheral blood lymphocytes (PBL) and their correlation with endometrial cell ITG expression in fertile and infertile women during peak uterine receptive period (day 19/20). METHOD OF STUDY: Surface marker expression and quantification of ,6, ,4 and ,3 ITG subunits was done by immunohistochemistry, indirect immunofluroscence and cell-enzyme-linked immunosorbent assay methods using endometrial cells and PBL obtained from fertile and infertile (unexplained infertility) women. RESULTS: The expression of ITGs was significantly (P<0.001) decreased in the endometrial cells of infertile women compared to normal fertile women. These results correlated well with the data obtained using PBL-ITG expression. CONCLUSIONS: If these preliminary data are consistent in a larger group of patients, the expression of ,4 and ,3-ITG subunits on PBL may be used as clinical markers to assess endometrial receptivity in infertile women. Moreover, frequent blood sampling is advantageous over repeated endometrial biopsies as the former approach is easier, non-traumatic and avoids intra-uterine infections. [source] The Elephant in the Room: Failings of Current Clinical Endpoints in Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010J. D. Schold In this opinion piece, we address the limitations of the two most common clinical endpoints in kidney transplantation trials (acute rejection and renal function) and attempt to offer a reasonable framework by which to find true and reliable early endpoints that reflect long-term outcomes. Other potential endpoints tested in recent years, including the use of genomic and proteomic markers are still in development. Until other reliable endpoints are established, it is important to understand what can be inferred from ongoing studies that utilize these endpoints and what further information we need to derive ,true' surrogate endpoints. We consider evaluation of current markers using the ,Prentice criteria', which bases assessment of endpoints as true surrogates on four primary rules. Based on our assessment, progress in understanding the safety and efficacy of new therapies and interventions in kidney transplantation will remain limited with current makers. Prospectively, we advocate: (i) significant caution in extrapolating long-term outcomes from currently utilized clinical markers, (ii) use of traditional hard endpoints whenever feasible and (iii) dedication of efforts for more data collection on specific disease entities and greater diligence in determining the onset of deleterious processes. [source] Impact of QT Variables on Clinical Outcome of Genotyped Hypertrophic CardiomyopathyANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 1 2009Katsuharu Uchiyama M.D. Background: Although QT variables such as its interval and/or dispersion can be clinical markers of ventricular tachyarrhythmia, few data exist regarding the role of QT variables in genotyped hypertrophic cardiomyopathy (HCM). Therefore, we analyzed QT variables in genotyped subjects with or without left ventricular hypertrophy (LVH). Methods: QT variables were analyzed in 111 mutation and 43 non-mutation carriers who were divided into three groups: A, those without ECG abnormalities and echocardiographically determined LVH (wall thickness ,13 mm); B, those with ECG abnormalities but LVH; and C, those with ECG abnormalities and LVH. We also examined clinical outcome of enrolled patients. Results: Maximal LV wall thickness in group C (19.0 ± 4.3 mm, mean ±SD) was significantly greater than that in group A (9.2 ± 1.8) and group B (10.4 ± 1.8). Under these conditions, maximum QTc interval and QT dispersion were significantly longer in group C than those in group A (438 ± 38 ms vs 406 ± 30 and 64 ± 31 vs 44 ± 18, respectively; P < 0.05). QTc interval and QT dispersion in group B (436 ± 50 and 64 ± 22 ms) were also significantly greater than those in group A. During follow-up periods, four sudden cardiac deaths and one ventricular fibrillation were observed in group C, and two nonlethal ventricular tachyarrhythmias were observed in group B. Conclusions: Patients with HCM-related gene mutation accompanying any ECG abnormalities frequently exhibited impaired QT variables even without LVH. We suggest that careful observation should be considered for those genotyped subjects. [source] Identifying Subjects Who Benefit from Additional Information for Better Prediction of the Outcome VariablesBIOMETRICS, Issue 3 2009L. Tian Summary Suppose that we are interested in using new bio- or clinical markers, in addition to the conventional markers, to improve prediction or diagnosis of the patient's clinical outcome. The incremental value from the new markers is typically assessed by averaging across patients in the entire study population. However, when measuring the new markers is costly or invasive, an overall improvement does not justify measuring the new markers in all patients. A more practical strategy is to utilize the patient's conventional markers to decide whether the new markers are needed for improving prediction of his/her health outcomes. In this article, we propose inference procedures for the incremental values of new markers across various subgroups of patients classified by the conventional markers. The resulting point and interval estimates can be quite useful for medical decision makers seeking to balance the predictive or diagnostic value of new markers against their associated cost and risk. Our proposals are theoretically justified and illustrated empirically with two real examples. [source] Cystatin-C and beta trace protein as markers of renal function in pregnancyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 5 2005Ayub Akbari Objective To assess the validity of Cystatin-C (Cys-C) and beta trace protein (BTP) as clinical markers of glomerular filtration rate (GFR) in pregnant women. Design Prospective cross sectional study. Setting Obstetric unit of a tertiary care hospital. Population One hundred and thirty-seven normal pregnant women and 13 women postpartum. Methods Twenty-four hour creatinine clearance (CrCl), serum creatinine, Cys-C and BTP concentrations were measured on normal pregnant women in the first trimester (n= 5), second trimester (n= 68) and third trimester (n= 64) and in 13 women postpartum. Data are given as median (2.5th centile, 97.5th centile). Main outcome measures Serum concentrations of Cys-C and BTP compared with creatinine clearance and serum creatinine. Results The median serum creatinine throughout gestation was 53 ,mol/L (39, 71), and median CrCl was 143 mL/minute (91 to 216). Postpartum, creatinine rose to 74 ,mol/L (58, 86) and CrCl decreased to 104 mL/minute (71, 159). For Cys-C, the median concentration was 0.70 mg/L (0.46, 1.32), and 0.54 mg/L (0.36, 0.96) for BTP. Comparing the second and third trimesters, there was no significant difference between CrCl (median 145 vs 141 mL/minute) and BTP concentrations (median 0.51 vs 0.55 mg/L), while median Cys-C was significantly higher in the third trimester (0.61 vs 0.88 mg/L; P < 0.001). Unlike creatinine and BTP, Cys-C levels decreased to 0.72 mg/L (0.57, 0.95) postpartum. The only significant relationship of either of these markers to the standard used for GFR was between Cys-C and CrCl in the third trimester, and the correlation was weak (r= 0.27 for 1/Cys-C vs CrCl). Conclusion These data demonstrate that despite claims to the contrary, Cys-C is a poor marker of GFR during pregnancy. Similarly, BTP shows little promise. [source] Electrolytic liver ablation is not associated with evidence of a systemic inflammatory response syndromeBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 2 2004B. D. Teague Background Local ablation has been proposed for treatment of liver tumours. Cryoshock, a variant of the systemic inflammatory response syndrome (SIRS), is a potentially fatal complication of cryoablation caused by systemic release of necrotic breakdown products from ablated liver. The proinflammatory cytokines tissue necrosis factor (TNF) , and interleukin (IL) 1 are important mediators of this response. This study assessed the risk of SIRS complicating electrolytic liver ablation by measuring circulating levels of inflammatory cytokines, other inflammatory markers and clinical markers of organ function. Methods Electrolytic liver ablation was performed in 16 pigs and four pigs served as controls. Platelet count, and serum levels of urea, creatinine, liver enzymes, C-reactive protein (CRP), TNF-, and IL-1, were measured before treatment and for 72 h after the procedure. Results There were significant dose-related increases in CRP and alanine aminotransferase levels with liver electrolysis. There was no significant derangement in renal function or platelet count following ablation. A rise in serum TNF-, and IL-1, levels was not associated with liver electrolysis. Conclusion There was no evidence of organ failure or significantly raised levels of proinflammatory cytokines as a result of liver electrolysis, suggesting that this is a safe procedure for liver ablation. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Determination of metastasis-associated proteins in non-small cell lung cancer by comparative proteomic analysisCANCER SCIENCE, Issue 8 2007Tian Tian The development of metastasis is the leading cause of death and an enormous therapeutic challenge in cases of non-small cell lung cancer. To better understand the molecular mechanisms underlying the metastasis process and to discover novel potential clinical markers for non-small cell lung cancer, comparative proteomic analysis of two non-small cell lung cancer cell lines with different metastatic potentials, the non-metastatic CL1-0 and highly metastatic CL1-5 cell lines, was carried out using two-dimensional electrophoresis followed by matrix-assisted laser desorption ionization,time of flight mass spectrometry and tandem mass spectrometry. Thirty-three differentially expressed proteins were identified unambiguously, among which 16 proteins were significantly upregulated and 17 proteins were downregulated in highly metastatic CL1-5 cells compared with non-metastatic CL1-0 cells. Subsequently, 8 of 33 identified proteins were selected for further validation at the mRNA level using real-time quantitative polymerase chain reaction, and three identified proteins, S100A11, PGP 9.5 and HSP27, were confirmed by western blotting. The protein S100A11 displaying significant differential expression at both the protein and mRNA levels was further analyzed by immunohistochemical staining in 65 primary non-small cell lung cancer tissues and 10 matched local positive lymph node specimens to explore its relationship with metastasis. The results indicated that the upregulation of S100A11 expression in non-small cell lung cancer tissues was significantly associated with higher tumor,node,metastasis stage (P = 0.001) and positive lymph node status (P = 0.011), implying that S100A11 might be an important regulatory molecule in promoting invasion and metastasis of non-small cell lung cancer. (Cancer Sci 2007; 98: 1265,1274) [source] Airway cell and cytokine changes in early asthma deterioration after inhaled corticosteroid reductionCLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2007Y. H. Khor Summary Background Back-titration of inhaled corticosteroid (ICS) dose in well-controlled asthma patients is emphasized in clinical guidelines, but there are few published data on the airway cell and cytokine changes in relation to ICS reduction. In our study, 20 mild-to-moderate persistent (inspite of low-moderate dose ICS treatment) asthmatic subjects prospectively rendered largely asymptomatic by high-dose ICS were assessed again by clinical, physiological, and airway inflammatory indices after 4,8 weeks of reduced ICS treatment. We aimed at assessing the underlying pathological changes in relation to clinical deterioration. Methods Patients recorded daily symptom scores and peak expiratory flows (PEF). Spirometry and airways hyperreactivity (AHR) were measured and bronchoscopy was performed with assessment of airway biopsies (mast cells, eosinophils, neutrophils, and T lymphoctyes), bronchoalveolar lavage (BAL) IL-5 and eotaxin levels and cellular profiles at the end of high-dose ICS therapy and again after ICS dose reduction. Baseline data were compared with symptomatic steroid-free asthmatics (n=42) and non-asthmatic controls (n=28). Results After ICS reduction, subjects experienced a variable but overall significant increase in symptoms and reductions in PEF and forced expiratory volume in 1 s. There were no corresponding changes in AHR or airways eosinophilia. The most relevant pathogenic changes were increased CD4+/CD8+ T cell ratio, and decreased sICAM-1 and CD18 macrophage staining (potentially indicating ligand binding). However, there was no relationship between the spectrum of clinical deterioration and the changes in cellular profiles or BAL cytokines. Conclusions These data suggest that clinical markers remain the most sensitive measures of early deterioration in asthma during back-titration of ICS, occurring at a time when AHR and conventional indices of asthmatic airway inflammation appear unchanged. These findings have major relevance to management and to how back-titration of ICS therapy is monitored. [source] Epidemiology and stratification of risk for sudden cardiac deathCLINICAL CARDIOLOGY, Issue S1 2005Philip J. Podrid M.D. Abstract Sudden cardiac death (SCD) is a major cause of mortality in the United States. Approximately 65% of cases of SCD occur in patients with underlying acute or chronic ischemic heart disease. The incidence of SCD increases 2- to 4-fold in the presence of coronary disease and 6- to 10-fold in the presence of structural heart disease. Ventricular fibrillation (VF) precipitated by ventricular tachycardia (VT) is a common mechanism of cardiac arrest leading to SCD. Triggers for SCD include electrolyte disturbances, heart failure, and transient ischemia. Although a large percentage of patients with out-of-hospital SCD do not survive, successful resuscitation to hospitalization has improved in recent years. One of the challenges for preventing SCD lies in identifying individuals at highest risk for SCD within a lower-risk population. The progression from conventional risk factors of coronary artery disease to arrhythmogenesis and SCD can be represented as a cascade of changes associated with levels of increasing risk. At the first level is atherogenesis, followed by changes in atherosclerotic plaque anatomy, which may be mediated by inflammatory processes. Disruption of active plaque formed during a transitional state initiates the thrombotic cascade and acute occlusion, after which acute changes in myocardial electrophysiology become the immediate trigger for arrhythmogenesis and SCD. Each level of the cascade offers different opportunities for risk prediction. Among the classes of risk predictors are clinical markers, such as ECG measures and ejection fraction. Transient risk markers, such as inflammatory markers, are potentially useful for identifying triggers for SCD. In the future, genetic profiling is expected to allow better assessment of individual risks for SCD. [source] |