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Poor Correlation (poor + correlation)
Selected AbstractsComparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemiaGENES, CHROMOSOMES AND CANCER, Issue 3 2004Alicja M. Gruszka-Westwood The functional consequences of a high-hyperdiploid karyotype, found in up to one-third of cases of acute lymphoblastic leukemia (ALL), are unknown. Using the technique of comparative expressed sequence hybridization (CESH), we sought to address the question of whether increased chromosome copies in hyperdiploid ALL lead to increased gene expression. Relative expression of hyperdiploid ALL blasts versus peripheral blood mononuclear cells was analyzed in 18 patients. Common regions of overexpression corresponding to the presence of tri-/tetrasomies included: Xp22.1,22.2, 4q28, 6q14,15, 6q24, 10p13, 14q23,24, 17q21, 18q12, and 21q21, identified in 28,89% of cases. However, increased expression without underlying trisomy occurred at 3p21.3, 7q11.2, 8p21, and 8q24.1 in 39,90% of cases. High expression at 7q11.2, the most consistent change detected, was confirmed by quantitative PCR. Poor correlation between the presence of tri-/tetrasomy and overexpression was observed for chromosomes 14 and 17. Two cases were reanalyzed versus (i) B cells, (ii) transformed B cells, and (iii) CD34+19+ cells (the putative counterpart of the leukemic cell). A reduction in the number of relatively overexpressed regions was observed with CD34+19+ cells. In particular, the peak at 7q11.2 disappeared, suggesting up-regulation of genes from this region in the early ontology of normal B-cell development. In conclusion, we have shown that tri-/tetrasomies in hyperdiploid ALL lead to an increase in the expression of associated sequences. The choice of a biologically relevant reference is crucial for data interpretation. © 2004 Wiley-Liss, Inc. [source] Poor correlation between clinical impression, the small colonic polyp and their neoplastic riskJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2006Ian Craig Lawrance Abstract Background and Objectives:, ,Significance of the small colonic polyp is unclear and its removal is frequently determined by the proceduralist's clinical impression. Our aims were to determine if clinical discernment is accurate, and the likelihood that lesions <,10 mm are histologically advanced. Method:, ,We prospectively collected 1988 lesions from 854 subjects (2215 consecutive colonoscopies). Lesion size, location, patient age, sex and the colonoscopist's clinical impression was recorded. Results:, Clinical assessment for neoplasia had a sensitivity of 87.4%, specificity of 65.0%, positive predictive value of 76.0% and negative predictive value of 80.2%, resulting in an accuracy of 73.4%. Factors predictive of correct clinical impression were polyp size, location in the rectum and being pedunculated, but not the patient's age, sex or the endoscopist's experience. Of the 1434 lesions ,,5 mm in size, 44.5% were neoplastic and 3.5% were histologically advanced. Of the 266 lesions 6,9 mm, 79.3% were neoplastic, 19.9% were histologically advanced, five demonstrated high-grade dysplasia and three were malignant. Only two patients with an adenocarcinoma or high-grade dysplasia in a polyp <10 mm had a lesion ,10 mm elsewhere in the colon. Of the 288 lesions ,10 mm in size, 92.7% were neoplastic, 29.5% had a villous component, 6.9% demonstrated high-grade dysplasia and 29.2% were malignant. Factors predictive of neoplasia were patient age, polyp size and sessile nature of the lesion. Conclusion:, Polyps <,10 mm had a significant risk of neoplasia and advanced histology and, in general, clinical impression correlated poorly with neoplasia. Removal of all lesions proximal to the rectum, regardless of size, should therefore be considered. [source] Enantioselectivity of thalidomide serum and tissue concentrations in a rat glioma model and effects of combination treatment with cisplatin and BCNUJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2007Susan Murphy Thalidomide is currently under evaluation as an anti-angiogenic agent in cancer treatment, alone and in combination with cytotoxic agents. Thalidomide is a racemate with known pharmacologic and pharmacokinetic enantioselectivity. In a previous study with thalidomide combination chemotherapy, we found evidence of anti-tumour synergy. In this study, we examined whether the synergy involved altered pharmacokinetics of thalidomide enantiomers. Adult female F344 rats were implanted with 9L gliosarcoma tumours intracranially, subcutaneously (flank), or both. Effectiveness of oral thalidomide alone, and with intraperitoneal BCNU or cisplatin combination chemotherapy, was assessed after several weeks treatment. Presumed pseudo steady-state serum, tumour and other tissues, collected after treatment, were assayed for R - and S -thalidomide by chiral HPLC. Both serum and tissue concentrations of R -thalidomide were 40,50% greater than those of S -thalidomide. Co-administration of BCNU or cisplatin with thalidomide did not alter the concentration enantioselectivity. Poor correlation of concentration with subcutaneous anti-tumour effect was found for individual treatments, and with all treatments for intracranial tumours. The consistency of the enantiomer concentration ratios across treatments strongly suggests that the favourable anti-tumour outcomes from interactions between thalidomide and the cytotoxic agents BCNU and cisplatin did not have altered enantioselectivity of thalidomide pharmacokinetics as their basis. [source] Liver biopsy results in patients with sickle cell disease on chronic transfusions: Poor correlation with ferritin levelsPEDIATRIC BLOOD & CANCER, Issue 1 2008Lina B. Karam MD Abstract Background: Chronic transfusions are effective in preventing stroke and other complications of sickle cell disease. The aim of this study was to determine whether serum ferritin levels correlated with liver iron content in sickle cell patients on chronic transfusion. Procedure: Forty-four liver biopsy specimens from 38 patients with homozygous sickle cell anemia (HbSS) and one patient with sickle thalassemia receiving chronic transfusions were studied. Five patients underwent a second liver biopsy for follow up. Three ferritin measurements were used to calculate a mean for each patient. The association between serum ferritin levels and liver iron quantitation was measured using the Spearman rank correlation, and sensitivity and specificity were determined for selected threshold values of serum ferritin. Results: Serum ferritin levels ranged from 515 to 6076 ng/ml, liver iron concentration ranged from 1.8 to 67.97 mg/g dry weight. The amount of iron per gram liver dry weight was moderately correlated with serum ferritin values (r,=,0.46). The correlation of duration of transfusion with serum ferritin (r,=,0.40) and with liver iron content (r,=,0.41) also indicated moderate correlation. Liver biopsy results led to changes in the management after 29/44 (66%) of the biopsies. Serum ferritin ,2500 ng/ml predicted high liver iron content (,7 mg/g), with a sensitivity of 62.5% and a specificity of 77.8%. Conclusion: We found a poor correlation between serum ferritin levels and liver iron content (LIC). Despite being on chelation therapy, many patients on chronic transfusion had high levels of liver iron. Measurement of LIC is highly recommended in these patients. Pediatr Blood Cancer 2008;50:62,65. © 2007 Wiley-Liss, Inc. [source] Prospective study of urine cytology screening for BK polyoma virus replication in renal transplant recipientsCYTOPATHOLOGY, Issue 6 2008M. Koukoulaki Objective:, BK virus (BKV) may be associated with interstitial nephritis in renal transplant recipients and this can lead to irreversible chronic allograft dysfunction. Early diagnosis of BKV nephropathy determines its progress because no specific antiviral therapy exists. Urine cytology, detection of viral DNA in urine or blood and renal biopsy are the main diagnostic tools. The purpose of this study was to evaluate the use of urine cytology for diagnosis of BKV replication in renal graft recipients. Patients and methods:, We studied 32 de novo renal transplant recipients prospectively with sequential urine samples for a period of 1 year. Thin-Prep methodology was used to prepare the slides. Cytology results were correlated with polymerase chain reaction (PCR) in urine and blood. Results:, Decoy cells indicative of BKV infection were detected in 14 (7.3%) of the 190 urine samples derived from 11 recipients. In three cases with positive decoy cells, BK viraemia and viruria were simultaneously identified. In a further three cases, BKV active replication was confirmed in urine by both cytology and PCR. Conclusions:, Urine cytology is an easy and rapid method of detecting decoy cells in cases where renal biopsy is not possible. However, the low incidence of detection of decoy cells in the present study, together with poor correlation with PCR results, questions its sensitivity and specificity in diagnosing BKV reactivation. [source] Interpretation of urinary concentrations of pseudoephedrine and its metabolite cathine in relation to doping controlDRUG TESTING AND ANALYSIS, Issue 5 2009K. Deventer Abstract Until the end of 2003 a urinary concentration of pseudoephedrine exceeding 25 µg/mL was regarded as a doping violation by the World Anti-Doping Agency. Since its removal from the prohibited list in 2004 the number of urine samples in which pseudoephedrine was detected in our laboratory increased substantially. Analysis of 116 in-competition samples containing pseudoephedrine in 2007 and 2008, revealed that 66% of these samples had a concentration of pseudoephedrine above 25 µg/mL. This corresponded to 1.4% of all tested in competition samples in that period. In the period 2001,2003 only 0.18% of all analysed in competition samples contained more than 25 µg/mL. Statistical comparison of the two periods showed that after the removal of pseudoephedrine from the list its use increased significantly. Of the individual sports compared between the two periods, only cycling is shown to yield a significant increase. Analysis of excretion urine samples after administration of a therapeutic daily dose (240 mg pseudoephedrine) in one administration showed that the threshold of 25 µg/mL can be exceeded. The same samples were also analysed for cathine, which has currently a threshold of 5 µg/mL on the prohibited list. The maximum urinary concentration of cathine also exceeded the threshold for some volunteers. Comparison of the measured cathine and pseudoephedrine concentrations only indicated a poor correlation between them. Hence, cathine is not a good indicator to control pseudopehedrine intake. To control the (ab)use of ephedrines in sports it is recommended that WADA reintroduce a threshold for pseudoephedrine. Copyright © 2009 John Wiley & Sons, Ltd. [source] Proximal Coronary Hemodynamic Changes Evaluated by Intracardiac Echocardiography during Myocardial Ischemia and Reperfusion in a Canine ModelECHOCARDIOGRAPHY, Issue 3 2008Beibei Han M.D. Background: The purpose of this study was to assess whether the dynamic changes in coronary flow velocity and coronary flow velocity reserve (CFVR) by intracardiac echocardiography (ICE) within proximal coronary arteries are related to myocardial perfusion status and infarct size in a myocardial ischemia-reperfusion injury model. Methods: In 14 dogs, left anterior descending coronary artery (LAD) was ligated for 2 hours followed by 2 hours reperfusion. Coronary flow velocity was obtained by ICE within coronary arteries at baseline, and at the end of both occlusion and reperfusion period. The CFVR was calculated as the ratio of hyperemic to resting peak diastolic velocity (PDV). Myocardial perfusion was evaluated by real time myocardial contrast echocardiography (MCE). The infarct area was detected by triphenyltetrazolium chloride (TTC) staining and expressed as the percentage of the whole left ventricular (LV) area. Results: CFVR significantly decreased both in proximal LAD and left circumflex (LCx) artery at the end of occlusion, and did not recover at the end of reperfusion. However, no significant difference in flow parameters was observed between dogs with myocardial perfusion defect and those without. CFVR in LAD at the end of reperfusion did not correlate with the infarct size (r =,0.182, P = NS) either. Conclusions: Decreased CFVR detected by ICE occurs both in ischemic and in nonischemic proximal arteries during myocardial ischemia and early stage of reperfusion. This change in CFVR has poor correlation with the extent of microvascular impairment and cannot be used to predict infarct size. [source] Comparison of Proximal Isovelocity Surface Area Method and Pressure Half Time Method for Evaluation of Mitral Valve Area in Patients Undergoing Balloon Mitral ValvotomyECHOCARDIOGRAPHY, Issue 9 2005Thottuvelil Narayanan Sunil Roy M.D. Background: The pressure half time (PHT) method is unreliable for measurement of mitral valve area (MVA) immediately after valvotomy. The proximal isovelocity surface area (PISA) method has been used to derive mitral valve area in patients with mitral stenosis. The aim of our study was to compare PISA method and PHT method in patients undergoing percutaneous balloon mitral valvotomy (BMV). Methods: The PISA was recorded from the apex and MVA was calculated using continuity equation by the formula 2,r2 Vr/Vm, where 2,r2 is the hemispheric isovelocity area, Vr is the velocity at the radial distance "r" from the orifice, and Vm is the peak velocity. A plain angle correction factor (,)/180 was used to correct the inlet angle subtended by leaflet tunnel as a result of leaflet doming. Results: MVA calculated using PISA method (r = 0.5217, P < 0.0001, SE = 0.016) and PHT (r = 0.6652, P < 0.0001, SE = 0.017) correlated well with 2D method in patients with mitral stenosis before BMV. After BMV, MVA by PISA method correlated well with 2D planimetry (r = 0.5803, P < 0.0001, SE = 0.053) but PHT showed poor correlation (r = 0.1334, P = 0.199, SE = 0.036). The variability of measurement of MVA was most marked with PHT method in the post-BMV period. Conclusion: The PISA method correlates well with 2D planimetry in patients with mitral stenosis before and after BMV and is superior to the PHT method in the post-BMV period where the latter may be unreliable. [source] Determination of tocopherols and phytosterols in sunflower seeds by NIR spectrometryEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 5 2007Alicia Ayerdi Gotor Abstract The objective of this work was to develop a near-infrared reflectance spectrometry (NIRS) calibration estimating the tocopherol and phytosterol contents in sunflower seeds. Approximately 1000 samples of grinded sunflower kernels were scanned by NIRS at 2-nm intervals from 400 to 2500,nm. For each sample, standard measurements of tocopherol and phytosterol contents were performed. The total tocopherol content was obtained by high-performance liquid chromatography coupled with a fluorescence detector, while the total phytosterol content was assessed by gas chromatography. For tocopherol, the calibration data set ranged from 175 to 1005,mg/kg oil (mean value around 510,±,140,mg/kg oil), whereas for the phytosterol content, the calibration data set ranged from 180 to 470,mg/100,g oil (mean value of 320,±,50,mg/100,g oil). The NIRS calibration showed a relatively good correlation (R2,=,0.64) between predicted by NIRS and real values for the total tocopherol content but a poor correlation for the total phytosterol content (R2,=,0.27). These results indicate that NIRS could be useful to classify samples with high and low tocopherol content. In contrast, the estimation of phytosterol contents by NIRS needs further investigation. Moreover, in this study, calibration was obtained by a modified partial least-squares method; the use of other mathematical treatments can be suitable, particularly for total phytosterol content estimation. [source] Comparison of near-infrared emission spectroscopy and the Rancimat method for the determination of oxidative stabilityEUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 1 2007Fabiano B. Gonzaga Abstract This work presents a comparison between a new method for the determination of the oxidative stability of edible oils at frying temperatures, based on near-infrared emission spectroscopy (NIRES), and the Rancimat method at 110,,°C. In the NIRES-based method, the induction time (IT) is determined by means of the variation of the emission band at 2900,nm during heating at 160,,°C. The comparison between the IT values obtained with the two methods for 12,samples of edible oils shows some correlation for samples of the same type once there is an agreement on the sequence of highest to lowest IT values between the methods, but a poor correlation considering all samples (correlation coefficient of 0.78). This lack of correlation demonstrates that the results obtained with the Rancimat method cannot be used as an indication of the oxidative stability, or the resistance to degradation, of edible oils at frying temperatures. The difference in the heating temperatures used in the two methods leads to 20,36,times higher IT values for the Rancimat method in relation to the NIRES-based method, but with similar repeatabilities (2.0 and 2.8%, respectively). [source] Accuracy and definitive interpretation of preoperative technetium 99m sestamibi imaging based on the discipline of the reader,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2009Ayesha N. Khalid MD Abstract Background. Technetium 99m sestamibi scans have become a principal means of localizing parathyroid adenomas. Its accuracy and reliability has allowed for the proliferation of minimal access parathyroidectomy. Localizing interpretation of these scans often drives referral of hyperparathyroid patients for surgery. Interpretation of these scans may differ between nuclear medicine physicians and surgeons. Methods. We reviewed patients (N = 65) with digital images from an academic medical center with the diagnosis of primary hyperparathyroidism. We assessed the willingness to define an adenoma's location, the interrater reliability, and the accuracy of technetium (Tc-99m) sestamibi read by a surgeon and a nuclear medicine physician. Results. There was poor correlation between both readers for assessment of quality of images (k = 0.54, 0.07) but very good correlation for adenoma location (k = 0.81). Conclusion. Both readers had good accuracy in predicting the location of the parathyroid adenoma. The surgeon was more likely to call a scan positive. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] Comparison of High Resolution Magnifying Endoscopy and Standard Videoendoscopy for the Diagnosis of Helicobacter pylori Gastritis in Routine Clinical Practice: A Prospective StudyHELICOBACTER, Issue 1 2009Can Gonen Abstract Background:, It has been shown that standard endoscopic features often labeled as gastritis has a poor correlation with histopathology. Recently, high resolution magnifying endoscopy has been reported to be an effective method to diagnose gastritis. The aim of the present study was to compare standard endoscopy with magnifying endoscopy for the diagnosis of Helicobacter pylori gastritis, and to determine whether gastritis can be diagnosed based on findings at magnification endoscopy. Materials and Methods:, A total of 129 patients were enrolled into the study. Erythema, erosions, prominent area gastrica, nodularity, and regular arrangement of collecting venules (RAC) were investigated by standard endoscopy. Standard endoscopy was followed by magnifying endoscopy in all patients, and repeated in 55 patients after indigo carmine spraying. Results:, None of the standard endoscopic features showed a sensitivity of more than 70% for H. pylori gastritis, except RAC pattern analysis. Absence of a corporal RAC pattern had 85.7% sensitivity and 82.8% specificity for predicting H. pylori infection. Under magnification, the sensitivity and specificity of regular corporal pattern (regular collecting and capillary vascular structures with gastric pits resembling pinholes) for predicting normal histology were 90.3% and 93.9%, respectively. Loss of collecting venules, or both collecting and capillary structures was correlated with chronic inflammation and activity. With the progression of mucosal atrophy, irregular collecting venules became visible. The values for irregularly arranged antral ridge pattern for the prediction of antral gastritis were 89.3% and 65.2%, respectively. Indigo carmine staining increased sensitivity and specificity up to 97.6% and 100% for corporal gastritis, and up to 88.4% and 75.0% for antral gastritis, respectively. Indigo carmine staining significantly increases the detection of intestinal metaplasia. Conclusions:, High resolution magnifying is superior to standard endoscopy for the diagnosis of H. pylori gastritis, and identification of specific histopathologic features such as atrophy and intestinal metaplasia seems possible. [source] Investigation of the correlation of sensitivity vectors of hydrogen combustion modelsINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2004Judit Zádor A well-established method for the analysis of large reaction mechanisms is the calculation and interpretation of the sensitivity of the kinetic model output Yi to parameter changes. Comparison of the sensitivity vectors si = {, Yi/,p} belonging to different model outputs is a new tool for kinetic analysis. The relationship of the sensitivity vectors was investigated in homogeneous explosions, freely propagating and burner-stabilized laminar flames of hydrogen,air mixtures, using either calculated adiabatic or constrained temperature profiles, for fuel-to-air ratios , = 0.5,4.0. Sensitivity vectors are called locally similar, if the relationship si = ,ijsj is valid, where ,ij is a scalar. In many systems, only approximate local similarity of the sensitivity vectors exists and the extent of it can be quantified by using an appropriate correlation function. In the cases of adiabatic explosions and burner-stabilized flames, accurate local similarity was present in wide ranges of the independent variable (time or distance), and the correlation function indicated that the local similarity was not valid near the concentration extremes of the corresponding species. The regions of poor similarity were studied further by cobweb plots. The correlation relationships found could be interpreted by the various kinetic processes in the hydrogen combustion systems. The sensitivity vector of the laminar flame velocity is usually considered to be characteristic for the whole combustion process. Our investigations showed that the flame velocity sensitivity vector has good correlation with the H and H2O concentration sensitivities at the front of the adiabatic flames, but there is poor correlation with the sensitivity vectors of all concentrations in homogeneous explosions. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 238,252 2004 [source] Attitudes towards skills examinations for basic surgical traineesINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 1 2005S.D. Bann Summary Objective measures of surgical skill and cognition are becoming available. A questionnaire study examining surgeons' beliefs towards a skills-based examination, current standards and possible benefits was devised. Three hundred pairs of standardised anonymous questionnaires were sent to consultants and their basic surgical trainees (BSTs) irrespective of surgical speciality. Responses were requested using a Likert scale (1,5, 3 = neutral response). Two-hundred and two replies were received (including 54 pairs). BST experience ranged from 6 to 60 months (mean 24 months). When questioned regarding current training in basic surgical skills, only 34% believed that they were given adequate training at present. Sixty-four per cent of respondents believed the introduction of a skills examination would raise standards and 66% believed it necessary. Eighty-three per cent of respondents believed that they or their BST would practice these skills, if an examination were introduced and 85% wanted or would provide dedicated teaching time for this. However, 68% had no access to a dedicated skills facility, and uptake of these, where available, was variable. When questioned about their ability to perform the six appropriate tasks, there was a poor correlation of scoring between the groups. Consultants and their BSTs do not believe that they are given adequate training in basic skills. The introduction of an examination would lead to practice of these skills and is seen as a positive move. [source] Morphological sperm defects analyzed by light microscopy and transmission electron microscopy and their correlation with sperm motilityINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2010Vincenzo Visco Objectives: To compare sperm defects as assessed by light microscopy (LM) and transmission electron microscopy (TEM), and to correlate them with sperm motility. Methods: A cohort of 40 male partners of infertile couples was selected. Group 1 (n = 31) included subjects with motility >5 and <50%, group 2 (n = 9) included those with motility <5% and the control group consisted of 10 normospermic subjects. Semen analysis of morphological parameters was carried out by LM and TEM. Results: A linear correlation between LM and TEM regarding head defects and excess residual cytoplasm (r = 0.87 and 0.90) was found, whereas there was a poor correlation between tail and midpiece anomalies (r = 0.46 and 0.21). No significant variations were detected by LM and TEM regarding sperm head defects and excess residual cytoplasm, whereas TEM showed a significantly greater percentage of tail and midpiece alterations compared with LM in groups 1 and 2, as well as controls (P < 0.05). The microtubular pattern ,<9 + 2' represented the most frequent axonemal morphological alteration. Conclusions: TEM might represent an additional diagnostic tool in the presence of severe sperm hypomotility or absence of motility. [source] Correlation of Left Atrial Diameter by Echocardiography and Left Atrial Volume by Computed TomographyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2 2009IRENE HOF M.D. Introduction: For patients undergoing catheter ablation of atrial fibrillation (AF), left atrial size is a predictor of recurrence of AF during follow-up. For this reason, major clinical trials have used a left atrial diameter (LAD) of more than 5.0 or 5.5 cm, assessed by echocardiography, as an exclusion criterion for patients deemed candidates for ablation of AF. However, whether LAD accurately reflects true left atrial size has not been systematically investigated. Therefore, the purpose of this study was to test the hypothesis that LAD, measured by echocardiography, accurately correlates to left atrial volume measured by computed tomography (CT). Methods and Results: We included 50 patients (mean age 56 ± 12 years, five female) with symptomatic AF (40% paroxysmal, 60% persistent), referred for catheter ablation. In each patient, transthoracic echocardiography was performed. Additionally, all patients underwent CT using a 64-slice CT scanner. Left atrial volume was calculated by manually tracing left atrial area on each CT cross-sectional image. Patients had a mean LAD measured by echocardiography of 4.5 ± 0.7 cm, ranging from 2.9 to 5.7 cm. Left atrial volume measured by CT ranged from 67 mL to 270 mL with a mean value of 146 ± 49 mL. A poor correlation was noted between LAD and left atrial volume, r = 0.49 (P < 0.001). Conclusion: LAD measured by echocardiography correlates poorly with left atrial volume measured by CT in patients with AF. As a result, selecting patients with AF for treatment with catheter ablation should not be based on an echocardiographic-derived LAD alone. [source] Population pharmacokinetic modelling of carbamazepine in epileptic elderly patients: implications for dosageJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2006I. B. Bondareva PhD Summary Background:, Proper use of antiepileptic drugs in the elderly involves knowledge of their pharmacokinetics to ensure a patient-specific balance between efficacy and toxicity. However, populations of epileptic patients on chronic carbamazepine (CBZ) therapy which have been studied have included data of relatively few elderly patients. Aims:, The aim of the present study was to evaluate the population pharmacokinetics of CBZ in elderly patients on chronic monotherapy. Methods:, We have used the non-parametric expectation maximization (NPEM) program in the USC*PACK collection of PC programs to estimate individual and population post-induction pharmacokinetics of CBZ in epileptic elderly patients who received chronic CBZ monotherapy. Age-related changes of CBZ population pharmacokinetics were evaluated from routine therapeutic drug monitoring (TDM) data of 37 elderly and 35 younger patients with epilepsy. As a ,historical control' we used previously published population modelling results from 99 young epileptic patients on chronic CBZ monotherapy. In that control group, TDM was performed in the same pharmacokinetic (PK) laboratory, using the same sampling strategy as in the present study, and the same PK population modelling software was used for data analysis. Results and conclusions:, A poor correlation was found between daily CBZ dose and serum concentrations in the elderly patients (r = 0·2, P = 0·25). Probably statistically significant difference in the median values of the CBZ metabolic rate constant (P < 0·001) between elderly and relatively young epileptic patients was found. Our results showed that age-related influences in CBZ pharmacokinetics in elderly patients should be considered in the optimal planning of CBZ dosage regimens. Most elderly patients with epilepsy will usually need CBZ dosages lower than those based on the median population PK parameter values obtained from younger patients. The present population model is also uniquely well suited for the new ,multiple model' design of dosage regimens to hit target therapeutic goals with maximum precision. [source] Calorie restriction reduces rDNA recombination independently of rDNA silencingAGING CELL, Issue 6 2009Michčle Riesen Summary Calorie restriction (CR) extends lifespan in yeast, worms, flies and mammals, suggesting that it acts via a conserved mechanism. In yeast, activation of the NAD-dependent histone deacetylase, Sir2, by CR is thought to increase silencing at the ribosomal DNA, thereby reducing the recombination-induced generation of extrachromosomal rDNA circles, hence increasing replicative lifespan. Although accumulation of extrachromosomal rDNA circles is specific to yeast aging, it is thought that Sirtuin activation represents a conserved longevity mechanism through which the beneficial effects of CR are mediated in various species. We show here that growing yeast on 0.05 or 0.5% glucose (severe and moderate CR, respectively) does not increase silencing at either sub-telomeric or rDNA loci compared with standard (2% glucose) media. Furthermore, rDNA silencing was unaffected in the hxk2,, sch9, and tor1, genetic mimics of CR, but inhibited by FOB1 deletion. All these interventions extend lifespan in multiple yeast backgrounds, revealing a poor correlation between rDNA silencing and longevity. In contrast, CR and deletion of the FOB1, HXK2, SCH9 and TOR1 genes, all significantly reduced rDNA recombination. This silencing-independent mechanism for suppressing rDNA recombination may therefore contribute to CR-mediated lifespan extension. [source] A comparison of Ktrans measurements obtained with conventional and first pass pharmacokinetic models in human gliomasJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2004Hamied A. Haroon MSc Abstract Purpose To compare in a group of patients with cerebral gliomas the estimates of Ktrans between a conventionally established pharmacokinetic model and a recently developed first pass method. Materials and Methods Glioma patients (23) were studied using T1 -weighted dynamic contrast-enhanced magnetic resonance imaging (MRI), and two alternative pharmacokinetic models were used for analysis to derive the volume transfer constant Ktrans. These were a modified version of the established model (yielding KTK) and a recently published method based on first pass leakage profile (FP) of contrast bolus (yielding Kfp). Results We found a strong correlation between intra-tumoral median KTK and Kfp (rho = 0.650, P < 0.01), but the values from the conventional model were consistently and significantly higher (mean of inter-tumoral Kfp and KTK medians were 0.018 minute,1 and 0.284 minute,1, respectively, P < 0.001). The spatial distribution of KTK and Kfp showed poor correlation in the presence of large vascular structures and good correlation elsewhere. Conclusion KTK and Kfp produce similar biologic information within voxels not dominated by vascular tissue. The FP method avoids erroneous overestimation of Ktrans in areas of significant intravascular contrast. Findings are in keeping with the predictions of previous mathematical simulations. J. Magn. Reson. Imaging 2004;19:527,536. © 2004 Wiley-Liss, Inc. [source] Temporal Variability of Ventricular Arrhythmias in Boxer Dogs with Arrhythmogenic Right Ventricular CardiomyopathyJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2009B.A. Scansen Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is prevalent in the Boxer. There is little information on the temporal variability of ventricular arrhythmias within affected dogs. Objective: To evaluate ambulatory electrocardiograms (AECG) from Boxers with ARVC for hourly variation in premature ventricular complexes (PVC) and heart rate (HR). Animals: One hundred and sixty-two Boxer dogs with ARVC. Methods: Retrospective, observational study of 1,181 AECGs collected from Boxer dogs at The Ohio State University from 1997 to 2004 was evaluated. The proportion of depolarizations that were PVCs was compared across each hour of the day, during six 4-hour periods of day, to the time after AECG application, and to the maximum and minimum HR. Results: A lower proportion of PVCs was noted during early morning (midnight to 0400 hours) as compared with the morning (0800,1200 hours) and late (1600,2000 hours) afternoon (P= .012). There was no increase in PVC proportion in the 1st hour after AECG application as compared with all other hours of the day (P= .06). There was poor correlation between maximum (,= 0.19) and minimum (,= 0.12) HR and PVC proportion. Conclusions and Clinical Importance: The likelihood of PVC occurrence in Boxer dogs with ARVC was relatively constant throughout the day, although slightly greater during the hours of 0800,1200 and 1600,2000. A biologically important correlation with HR was not apparent. The role of autonomic activity in the modulation of electrical instability in the Boxer with ARVC requires further study. [source] Pain versus discomfort,is differentiation clinically useful?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2001V. Stanghellini Functional dyspepsia is highly variable in its clinical presentation and multifactorial in its underlying causes. Since many of the symptoms included in the definition of dyspepsia are intuitively suggestive of different pathogenic mechanisms, it has been proposed that patients with functional dyspepsia be divided into distinct dyspepsia sub-groups according to symptom clusters. The goal was to classify patients more homogeneously for research purposes as well as to target treatment. However, recent epidemiological, pathophysiological, and clinical studies indicate that a priori definitions based on the presence/absence of symptoms or clusters of symptoms have no clinical utility due to the considerable overlap between symptoms, as well as the poor correlation between pathogenic factors and responses to treatment. Attention is now focused on identifying predominant symptoms. Recent studies suggest that the analysis of predominant symptoms, demographic features, and overlapping digestive syndromes can help to identify dyspepsia sub-groups with different underlying pathophysiological features and aid in selecting appropriate treatment. The utility of this approach has been demonstrated in gastro-oesophageal reflux disease, which can be reliably diagnosed and managed on the basis of the presence and severity of the predominant symptom, heartburn. It is likely that precise symptom definitions and history-taking will be of pivotal importance in management strategies for functional dyspepsia. [source] Strain Energies as a Steric Descriptor in QSAR CalculationsMOLECULAR INFORMATICS, Issue 7 2004Catherine Abstract The difference between the calculated heats of formation of gauche and anti conformers of monosubstituted propanes was determined and used as a new steric parameter (AG60 value) in QSAR calculations. The dihedral angle of the gauche conformation was fixed at 60° during the calculation to force interaction of the gauche groups. AG60 values are a thermodynamically determined steric measure in contrast to the Taft steric parameter, which is based upon kinetic measurements of ester hydrolyses. In comparisons to published QSAR studies, AG60 values correlated steric effects and biological activities very similarly to the Taft parameter. The average of r2 values from five QSAR studies for the Taft parameter was 0.887, while AG60 values averaged 0.883. Direct comparison of the Taft parameter and AG60 values showed a poor correlation (r2=0.300), indicating the two parameters are fundamentally different methods of measuring steric bulk. [source] Motor evoked potentials from the pelvic floorNEUROUROLOGY AND URODYNAMICS, Issue 7 2003Sřren Brostrřm Proper function of the lower urinary tract depends on the integrity of the central and peripheral nervous pathways on multiple levels, and the complexity of this system leaves it susceptible to even minor lesions. While dysfunction of the lower urinary tract is prevalent amongst patients with nervous system disease, e.g., multiple sclerosis (MS), most women with lower urinary tract dysfunction (LUTD) have no overt neurological cause. Refined neuro-diagnostic approaches are needed to reveal neurogenicity in these patients. A potential method is transcranial magnetic stimulation (TMS), which is used routinely to test the motor innervation of limb muscles, but also can be applied to test pelvic floor efferents. To resolve the lack of methodological clarity and the need for normative values for the use of pelvic floor motor evoked potentials (MEPs), 30 healthy women and 16 women with MS were studied. Methods The healthy women underwent MEP studies with various stimulus and recording modalities, and, to test reproducibility, 18 of them were retested at a separate session. The women with MS underwent MEP testing as well as urodynamic studies. Results From the methodological studies of healthy women, the use of invasive concentric needle electrodes was found to be superior to surface electrodes. When applying magnetic stimuli over the sacral region, various methodological problems were encountered. In the healthy women, a large variability of responses was noted, the long-term reproducibility of pelvic floor MEP latencies was poor, and in some cases responses could not be obtained. In the study of women with MS, prolonged central conduction times were found, along with many cases of unevokable responses, and a poor correlation of MEPs to urodynamic findings. The problems of obtaining selective recordings from the inaccessible pelvic floor musculature are discussed, and possible sources of variability in MEPs from the pelvic floor are considered. By relating the findings in the present studies to those of others using different modalities, some reflections are presented on the nature of the neural pathways to the pelvic floor activated by magnetic stimulation. As unevokable responses from the pelvic floor were an occasional finding among the healthy women, it is argued that a pelvic floor non-response in a patient with suspected corticospinal lesion should be interpreted with care, and should not carry the same clinical significance as an absent limb response. Conclusions The inherent limitations of pelvic floor MEPs are discussed, and it is concluded that while there seems to be only limited clinical value of pelvic floor MEP testing, there might be some interesting scientific perspectives in studies that aim to control and explain the variability of responses. Neurourol. Urodynam. 22:620,637, 2003. © 2003 Wiley-Liss, Inc. [source] ECG Leads I and II to Evaluate Diuresis of Patients with Congestive Heart Failure Admitted to the Hospital via the Emergency DepartmentPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2009SUTHAPORN LUMLERTGUL M.D. Background: Attenuation of electrocardiogram (ECG) QRS complexes is observed in patients with a variety of illnesses and peripheral edema (PERED), and augmentation with alleviation of PERED. Serial ECGs in stable individuals display variation in the amplitude of QRS complexes in leads V1,V6, stemming from careless placement of recording electrodes on the chestwall. Electrocardiographs record only leads I and II, and mathematically derive the other four limb leads in real time. This study evaluated the sum of the amplitudes of ECG leads I and II, along with other sets of ECG leads in the monitoring of diuresis in patients with congestive heart failure (CHF). Methods: Twenty patients with CHF had ECGs and weights recorded on admission and at discharge. The amplitude of the QRS complexes in all ECG leads were measured and sums of I and II, all limb leads, V1,V6, and all 12 leads were calculated. Results: There was a good correlation between the weight loss and the increase in the sums of the amplitudes of the QRS complexes from leads I and II (r = 0.55, P = 0.012), and the six limb leads (r = 0.68, P = 0.001), but a poor correlation with the V1,V6 leads (r = 0.04, P = 0.85) and all 12 leads (r = 0.1, P = 0.40). Conclusions: Sums of the amplitudes of the ECG QRS complexes from leads I and II constitute a reliable, easily obtainable, ubiquitously available, bedside clinical index, which can be employed in the diagnosis, monitoring of management, and follow-up of patients with CHF. [source] Liver biopsy results in patients with sickle cell disease on chronic transfusions: Poor correlation with ferritin levelsPEDIATRIC BLOOD & CANCER, Issue 1 2008Lina B. Karam MD Abstract Background: Chronic transfusions are effective in preventing stroke and other complications of sickle cell disease. The aim of this study was to determine whether serum ferritin levels correlated with liver iron content in sickle cell patients on chronic transfusion. Procedure: Forty-four liver biopsy specimens from 38 patients with homozygous sickle cell anemia (HbSS) and one patient with sickle thalassemia receiving chronic transfusions were studied. Five patients underwent a second liver biopsy for follow up. Three ferritin measurements were used to calculate a mean for each patient. The association between serum ferritin levels and liver iron quantitation was measured using the Spearman rank correlation, and sensitivity and specificity were determined for selected threshold values of serum ferritin. Results: Serum ferritin levels ranged from 515 to 6076 ng/ml, liver iron concentration ranged from 1.8 to 67.97 mg/g dry weight. The amount of iron per gram liver dry weight was moderately correlated with serum ferritin values (r,=,0.46). The correlation of duration of transfusion with serum ferritin (r,=,0.40) and with liver iron content (r,=,0.41) also indicated moderate correlation. Liver biopsy results led to changes in the management after 29/44 (66%) of the biopsies. Serum ferritin ,2500 ng/ml predicted high liver iron content (,7 mg/g), with a sensitivity of 62.5% and a specificity of 77.8%. Conclusion: We found a poor correlation between serum ferritin levels and liver iron content (LIC). Despite being on chelation therapy, many patients on chronic transfusion had high levels of liver iron. Measurement of LIC is highly recommended in these patients. Pediatr Blood Cancer 2008;50:62,65. © 2007 Wiley-Liss, Inc. [source] Spontaneous platelet aggregation in Kawasaki disease using the particle counting methodPEDIATRICS INTERNATIONAL, Issue 6 2003Masashi Taki AbstractBackground:,Platelet aggregation is generally measured by the optical density method. This method is not very sensitive in detecting platelet activation because of the poor correlation between the formation of platelet aggregates and light transmission, and inability to detect small platelet aggregates. Recently, a new method was developed that detects small platelet aggregates formed in the early phase of platelet aggregation by means of a particle counting technique using light scattering. Methods:,The present study used the particle counting method to measure spontaneous platelet aggregation (SPA) produced by agitation with a stirrer bar without agonists in patients with Kawasaki disease (KD) and children's thrombotic disease, and compared the results with the conventional optical density method. Results:,Using the particle counting method, significantly higher SPA rates were found before treatment than in healthy adults and at the other stages of treatment. A similar tendency was noted with the optical density method; however, the positive rate of SPA was significantly higher with the particle counting method in each stage except the second stage, which was the period from the start of gamma-globulin therapy to 20 days. Conclusion:,These results indicate that enhanced platelet aggregation is noted at a high frequency before treatment of KD and that the particle counting method is superior to the optical density method in detecting enhanced platelet aggregation. [source] 2-D protein maps of rat gastrocnemius and soleus muscles: A tool for muscle plasticity assessmentPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 1 2006Cecilia Gelfi Dr. Abstract Functional characterization of muscle fibers relies on ATPase activity and on differential measurements of metabolic proteins, including mitochondrial and glycolytic enzymes, glucose, lactate and lactic acid transporters, calcium cycling proteins and components of the contractile machinery. The recent introduction of microarray technology has enabled detailed gene expression studies under different physiological and pathological conditions, thus generating novel hypotheses on muscle function. However, microarray approaches are limited by the incomplete genome coverage of currently available chips, and by poor correlation between mRNA concentration and protein expression level. We have used 2-DE and MS to build a reference map of proteins from rat mixed gastrocnemius and soleus muscle, and to assess qualitative and quantitative differences in protein distribution between these two functionally dissimilar muscles. More than 800 spots on each gel were detected by silver staining, of which 167 were excised, digested in-gel with trypsin and analyzed by ESI-MS/MS. One hundred and twenty eight distinct gene products were identified, including metabolic, transport and contractile proteins. Forty one spots displayed differences in relative expression level between mixed gastrocnemius and soleus samples. These data not only enable differentiation of functionally distinct slow-twitch and fast-twitch fiber types, but also provide tools for investigating muscle plasticity in response to physiological and environmental conditions such as aging or hypoxia. [source] A transcriptomic and proteomic analysis of the effect of CpG-ODN on human THP-1 monocytic leukemia cellsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2005Cheng-Chin Kuo Abstract The CpG motif of bacterial DNA (CpG-DNA) is a potent immunostimulating agent whose mechanism of action is not yet clear. Here, we used both DNA microarray and proteomic approaches to investigate the effects of oligodeoxynucleotides containing the CpG motif (CpG-ODN) on gene transcription and protein expression profiles of CpG-ODN responsive THP-1 cells. Microarray analysis revealed that 2,h stimulation with CpG-ODN up-regulated 50,genes and down-regulated five genes. These genes were identified as being associated with inflammation, antimicrobial defense, transcriptional regulation, signal transduction, tumor progression, cell differentiation, proteolysis and metabolism. Longer stimulation (8,h) with CpG-ODN enhanced transcriptional expression of 58,genes. Among these 58,genes, none except one, namely WNTI inducible signaling pathway protein,2, was the same as those induced after 2,h stimulation. Proteomic analysis by two-dimensional gel electrophoresis, followed by mass spectrometry identified several proteins up-regulated by CpG-ODN. These proteins included heat shock proteins, modulators of inflammation, metabolic proteins and energy pathway proteins. Comparison of microarray and proteomic expression profiles showed poor correlation. Use of more reliable and sensitive analyses, such as reverse transcriptase polymerase chain reaction, Western blotting and functional assays, on several genes and proteins, nonetheless, confirmed that there is indeed good correlation between mRNA and protein expression after CpG-ODN treatment. This study also revealed that several anti-apoptotic and neuroprotective related proteins, not previously reported, are activated by CpG-DNA. These findings have extended our knowledge on the activation of cells by CpG-DNA and may contribute to further understanding of mechanisms that link innate immunity with acquired immune response(s). [source] Differential Antibody Recognition of Four Allelic Variants of the Merozoite Surface Protein-2 (MSP-2) of Plasmodium falciparumTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 5 2001RENATA TONHOSOLO ABSTRACT. The merozoite surface protein-2 (MSP-2) is a major vaccine candidate for the asexual blood stage of Plasmodium falciparum. MSP-2 is essentially dimorphic, and allelic families are named after the representative isolates FC27 and IC1. The polymorphic central region contains immunodominant repeats, which vary in number, length, and sequence within and between allelic families. We have examined the antibody recognition of repeat regions from both MSP-2 allelic families expressed as recombinant fusion peptides. The results are summarized as follows. (1) Immunization of mice with the fusion peptides elicited IgG antibodies that cross-reacted with the native MSP-2 molecule in an allelic family-specific manner. (2) These mouse antibodies recognized the recombinant proteins in both a variant-specific and a family-specific manner, as shown in inhibition immunoassays. Antibodies raised against the peptide FC27 seemed to be essentially variant-specific, since the soluble form of the S20 antigen (a member of FC27 family) had relatively little inhibitory effect on them. (3) The overall pattern of human IgG antibody responses to MSP-2 in Karitiana Indians, a population continuously exposed to hypoendemic malaria in the Brazilian Amazon Region, differs from that described in hyperendemic areas in Africa and Papua New Guinea in two important features: there was no clear age-dependent increase in the prevalence and mean concentration of specific IgG antibodies, and there was no skewing towards the IgG, subclass in antibody responses. (4) The relatively poor correlation between concentrations of IgG antibodies that are specific for members of the same allelic family suggests that recognition of MSP-2 peptides by naturally acquired antibodies was largely variant-specific in this population. The potential role of naturally acquired variant-specific antibodies in immune evasion, by selecting mutant parasites carrying insertions or deletions of repeat sequences, is briefly discussed. [source] Validation of a bedside activated clotting time test (Hemochron® Jr II Signature) with low dose heparin therapyANAESTHESIA, Issue 4 2009L. Racioppi Summary The purpose of this study was to validate a device designed to measure activated clotting time in low-range heparin plasma concentrations (ACT-LR) prospectively during the post-operative period of vascular surgery. Measurement of ACT-LR and activated partial thromboplastin time (APTT) were performed before heparinisation (T0) and at the end of surgery (T1). ACT-LR(T1) and ,ACT-LR (defined as ACT-LR(T1) , ACT-LR(T0)) were evaluated as diagnostic tests for excessive anticoagulation, defined by APTT more than twice the laboratory's normal, by Bland-Altman method and receiver operating characteristic (ROC) curves. In 103 patients, mean (SD) ACT-LR was 137 (33) s at T0 and 176 (39) s at T1. Bland-Altman graph did not show a good agreement between APTT and ACT-LR. Areas under ROC curves were 0.82 (95% CI: 0.75,0.89) and 0.87 (95% CI: 0.80,0.93) for ACT-LR(T1) and ,ACT-LR, respectively. Using a threshold of 32 s for ,ACT-LR, test sensitivity was 87% (95% CI: 81,93%), specificity was 85% (95% CI: 78,92%), positive predictive value was 90% (95% CI: 84,96%) and negative predictive value was 81% (95% CI: 73,86%). While ,ACT-LR may have some potential in evaluating excessive anticoagulation in vascular surgery, the poor correlation between ACT-LR and APTT does not support its routine use. [source] |