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Discordant Results (discordant + result)
Selected AbstractsMeasurement of HIV RNA in patients infected by subtype C by assays optimized for subtype B results in an underestimation of the viral loadJOURNAL OF MEDICAL VIROLOGY, Issue 2 2004Bat-Sheva Gottesman Abstract Quantitation assays of HIV-1 RNA used currently were designed and optimized for subtype B viruses. However, infection with non-B HIV viruses has become more common worldwide. Unfortunately, little information is available regarding the suitability of these assays for measurement of viral load in specific non-B subtypes. The performance of two commercial HIV-1 RNA quantitation assays was evaluated in 82 HIV subtype C-infected patients and in 43 HIV-1 subtype B-infected patients. Blood samples were tested by the Amplicor HIV-1 Monitor Assay, Version 1.5, and by the nucleic acid sequence-based amplification HIV-1 assay (NucliSens). The results were compared by using a paired, two-tailed Student's t -test; the difference between the assays was found to be significant only for subtype C. Discordant results (>0.5 log difference) between the two assays were detected in 39% of subtype C samples, compared to 23.2% of subtype B samples. In all cases in which a discordant result was detected, the lower results were obtained by the NucliSens assay. Discordant results between CD4 and viral load (CD4,<,200 cells/ml with a viral load <5,000 copies/ml) were observed in eight of the subtype C-infected patients when a viral load was measured by NucliSens (9.7%), compared to three patients (3.6%) when measured by the Amplicor assay. In conclusion, in patients with HIV subtype C infection, measurement of HIV RNA by the NucliSens assay resulted in a significant underestimation of the viral load as compared to the Amplicor assay. As a consequence, such an underestimation may result in sub-optimal care of patients infected with HIV subtype C. J. Med. Virol. 73:167,171, 2004. © 2004 Wiley-Liss, Inc. [source] Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD geneBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2007M. Méndez Summary Background, Porphyria cutanea tarda (PCT) results from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. In the majority of patients, the disease is sporadic (S-PCT or type I) and the enzyme deficiency is limited to the liver. Familial PCT (F-PCT or type II) is observed in 20,30% of patients in whom mutations on one allele of the UROD gene reduce UROD activity by approximately 50% in all tissues. Another variant of PCT (type III) is characterized by family history of the disease although it is biochemically indistinguishable from S-PCT. Objectives, To investigate the molecular basis of PCT in Spain and to compare enzymatic and molecular analysis for the identification of patients with F-PCT. Methods, Erythrocyte UROD activity measurement and mutation analysis of the UROD gene were carried out in a cohort of 61 unrelated Spanish patients with PCT and 50 control individuals. Furthermore, each novel missense mutation identified was characterized by prokaryotic expression studies. Results, Of these 61 patients, 40 (66%) were classified as having S-PCT, 16 (26%) as having F-PCT and five (8%) as having type III PCT. Discordant results between enzymatic and molecular analysis were observed in two patients with F-PCT. In total, 14 distinct mutations were found, including 10 novel mutations: five missense, one nonsense, three deletions and an insertion. Prokaryotic expression of the novel missense mutations demonstrated that each results in decreased enzyme activity or stability. Conclusions, These results confirm the high degree of molecular heterogeneity of F-PCT in Spain and emphasize the usefulness of molecular genetic analysis to distinguish between F-PCT and S-PCT. [source] 2263: Analysis of the utility of QuantiFERON-TB GoldTM in tube and measurement of IFN, release by peripheral mononuclear cells in response to different mycobacterium antigen in the work-up of patients with uveitisACTA OPHTHALMOLOGICA, Issue 2010D MAKHOUL Purpose Tuberculosis remains an important cause of infectious uveitis and immune reaction against mycobacteria may contribute to the development of certain forms of autoimmune uveitis. Moreover, many non-infectious uveitis patients are treated with immunomodulatory treatment. The evaluation of tuberculosis immunity is thus an important aspect in the work-up of patients with uveitis. In this work, we would like to investigate the usefulness of different methods of tuberculosis immunity testing in a series of patients with intraocular inflammation. Methods Patients with uveitis will undergo a standard diagnosis procedure, including a chest Xray. Quantiferon TB Gold in Tube (QFT) and tuberculin skin test (TST) will be performed. IFN, production by mononuclear cells in response to PPD and to HBHA will be measured by ELISA. Results Thirty-two patients have already been recruited. Sixteen had a negative QFT and a negative TST. In two of them, mononuclear cells produce IFN, in response to PPD (but not to HBHA) and in 1 in response to HBHA (but not to PPD). In 11 patients QFT and TST were positive. In this group, IFN, response to PPD was observed in 82% but only in 50% in response to HBHA. Discordant results between QFT and TST were observed in 5 patients. One had a positive QFT and a negative TST and 4 had a positive TST and a negative QFT. In this group IFN, response to PPD or HBHA was not observed. Conclusion Discordant results between QuantiFERON-TB Gold and TST were observed in 15 % of uveitis patients. Analysis of the IFN, production in response to PPD and to HBHA seems to add important information in both concordant and discordant group. [source] Measurement of HIV RNA in patients infected by subtype C by assays optimized for subtype B results in an underestimation of the viral loadJOURNAL OF MEDICAL VIROLOGY, Issue 2 2004Bat-Sheva Gottesman Abstract Quantitation assays of HIV-1 RNA used currently were designed and optimized for subtype B viruses. However, infection with non-B HIV viruses has become more common worldwide. Unfortunately, little information is available regarding the suitability of these assays for measurement of viral load in specific non-B subtypes. The performance of two commercial HIV-1 RNA quantitation assays was evaluated in 82 HIV subtype C-infected patients and in 43 HIV-1 subtype B-infected patients. Blood samples were tested by the Amplicor HIV-1 Monitor Assay, Version 1.5, and by the nucleic acid sequence-based amplification HIV-1 assay (NucliSens). The results were compared by using a paired, two-tailed Student's t -test; the difference between the assays was found to be significant only for subtype C. Discordant results (>0.5 log difference) between the two assays were detected in 39% of subtype C samples, compared to 23.2% of subtype B samples. In all cases in which a discordant result was detected, the lower results were obtained by the NucliSens assay. Discordant results between CD4 and viral load (CD4,<,200 cells/ml with a viral load <5,000 copies/ml) were observed in eight of the subtype C-infected patients when a viral load was measured by NucliSens (9.7%), compared to three patients (3.6%) when measured by the Amplicor assay. In conclusion, in patients with HIV subtype C infection, measurement of HIV RNA by the NucliSens assay resulted in a significant underestimation of the viral load as compared to the Amplicor assay. As a consequence, such an underestimation may result in sub-optimal care of patients infected with HIV subtype C. J. Med. Virol. 73:167,171, 2004. © 2004 Wiley-Liss, Inc. [source] Discrepancy in measuring CD4 expression on T-lymphocytes using fluorescein conjugates in comparison with unimolar CD4-phycoerythrin conjugates,,CYTOMETRY, Issue 6 2007Lili Wang Abstract Background: Numerous methods for quantitative fluorescence calibration (QFC) have been developed to quantify receptor expression on lymphocytes. However, the results from the use of these different QFC methods vary considerably in the literature. To better identify the causes of these discrepancies, we measured CD4 expression using FITC and phycoerythrin (PE) conjugates to stain CYTO-TROLŌ Control Cells and T-lymphocytes in whole blood and isolated cell preparations. We further examined pH of the cellular microenvironment as a cause of discordant results obtained with the FITC conjugate. Methods: Calibration with Quantibrite PE-labeled microspheres and the use of unimolar CD4-PE conjugates provided direct measurement of the antibody bound per cell value (ABC) for CD4 expression on normal T-lymphocytes. Calibration for CD4-FITC monoclonal antibody (Mab) labeled CYTO-TROL Control Cells and normal T-lymphocytes was based on molecules of equivalent soluble fluorochrome (MESF) as determined by FITC-labeled microspheres traceable to NIST RM 8640. The MESF value for CD4-FITC Mab was determined that enabled the conversion of the MESF values obtained for CYTO-TROL cells to ABC. We investigated the likely pH change in the fluorescein microenvironments within FITC-labeled Mab and cells stained with FITC-labeled Mab using a pH sensitive indicator. Results: The mean ABC value for T-lymphocytes prepared from fresh whole blood using CD4-PE conjugate (48,321) was consistent with previous results, and it was much higher than the mean ABC using CD4-FITC Mab (22,156). The mean ABC value for CYTO-TROL cells using CD4-PE conjugate (43,090) was also higher than that using CD4-FITC conjugate (34,734), although the discrepancy was not as great. Further studies suggested the discrepancy in CYTO-TROL results may be accounted for by the low pH of the membrane microenvironment, but the greater discrepancy in T-lymphocytes could not be fully explained. Conclusion: CD4 expression on fresh normal whole blood samples and CYTO-TROL cells can be consistently quantified in ABC units using Quantibrite PE quantification beads and unimolar CD4-PE conjugates. Quantification with CD4-FITC conjugate is not as consistent, but may be improved by the use of CD4 T-cells as biological calibrators. This approximation is valid only for surface receptors with consensus ABC values measured by different QFC methods serving as biological standards. Published 2007 Wiley-Liss, Inc. [source] Comparison of bone marrow and peripheral blood ZAP-70 status examined by flow cytometric immunophenotyping in patients with chronic lymphocytic leukemiaCYTOMETRY, Issue 4 2006Rachel Sheridan Abstract Background: The mutational status of the immunoglobulin heavy chain variable gene in patients with chronic lymphocytic leukemia correlates with prognosis. Patients with mutated IgVH genes fare better than those with unmutated genes. Gene expression profiling studies identified the tyrosine kinase ZAP-70 to be expressed in unmutated CLL samples. Flow cytometric examination of ZAP-70 expression in tumor cells has been proposed to be a convenient surrogate marker for IgVH mutational status. However, a few studies have shown a small number of discordant results between ZAP-70 positivity, IgVH mutational status, and clinical outcome. There have been no reported studies comparing bone marrow samples with peripheral blood for ZAP-70 expression in CLL patients. Methods: We searched our flow cytometry files from October 2004 through April 2006 and identified CLL in 311 bone marrow and peripheral blood specimens from 256 patients. We defined ZAP-70 positivity as greater than 30% of the CD19+ B-cells above the isotype control value that coexpress ZAP-70. Statistical analyses were performed using the Fisher exact test and student t -test. Results: A significantly greater number of bone marrow specimens were positive for ZAP-70 when compared with the number of peripheral blood specimens. Of all the ZAP-70 negative specimens, CLL cells from bone marrow had a greater mean percentage of ZAP-70 positive cells when compared with the CLL cells from peripheral blood. Finally, six patients were identified who were ZAP-70 positive in the bone marrow but ZAP-70 negative in the peripheral blood. Conclusions: These results may be due to either an increase in the false positive rate in bone marrow specimens or to an intrinsic feature of CLL cells in the compartment that is biologically distinct from peripheral tumor cells. As prognosis and treatment decisions may be based on ZAP-70 results from either specimen type, it is prudent to further examine this observation. © 2006 International Society for Analytical Cytology [source] Plasma nitrotyrosine levels, antioxidant vitamins and hyperglycaemiaDIABETIC MEDICINE, Issue 9 2005S. Bo Abstract Aims Studies on plasma nitrotyrosine (NT) levels, a measure of oxidative injury, in diabetes are limited and discordant; the amount of antioxidants might represent a possible explanation for the discordant results. The aim of this paper is to evaluate the association between plasma NT levels and glucose tolerance status, according to antioxidant vitamin intakes. Methods In three hundred men randomly selected from a population-based cohort, NT levels were measured and dietary intake assessed by a food-frequency questionnaire. Results NT values were similar in patients with diabetes (n = 34), impaired fasting glucose (n = 77) and normoglycaemic subjects (n = 189). However, in subjects with lower than recommended daily intakes of antioxidant vitamins C and A, NT levels were significantly higher in the diabetic patients. In a multiple regression model, after adjustments for age, body mass index (BMI) and smoking habits, NT levels were significantly associated with fasting glucose in patients with lower intakes of vitamin C (, = 11.4; 95% CI 1.3 21.5) and vitamin A (, = 14.9; 95% CI 3.9 25.9), but not in subjects with lower intake of vitamin E. Conclusion A significant positive correlation between NT levels and fasting glucose is evident only in the presence of a reduced intake of some antioxidant vitamins. These findings might explain, at least in part, the discrepant results of previous studies and, if confirmed by further studies, suggest a simple measure (a balanced diet) to alleviate the increased oxidative stress of diabetes. [source] Genetic variability in Irish populations of the invasive zebra mussel, Dreissena polymorpha: discordant estimates of population differentiation from allozymes and microsatellitesFRESHWATER BIOLOGY, Issue 7 2008ELIZABETH GOSLING Summary 1. The recent arrival and explosive spread of the zebra mussel, Dreissena polymorpha (Pallas), in Ireland provided a rare opportunity to study the population genetics of an invasive species. 2. Eight polymorphic allozyme loci (ACO-1, ACO-2, EST-D, GPI, IDH-2, MDH, OPDH and PGM) were used to investigate genetic diversity and population structure in five Irish populations, and the results were compared with those from a previous microsatellite study on the same samples. 3. The mean number of alleles per locus (2.7 ± 0.1) was similar to the mean for the same loci in European populations, suggesting that Irish founder populations were large and/or multiple colonization events took place after foundation. A deficiency of heterozygotes was observed in all populations, but was uneven across loci. 4. Pairwise comparisons, using Fisher's exact tests and FST values, revealed significant genetic differentiation among populations. The overall multilocus FST estimate was 0.118 ± 0.045, which contrasted with an estimate of 0.015 ± 0.007 from five microsatellite loci on the same samples in a previous study. 5. Assuming that microsatellites can be used as a neutral baseline, the discordant results from allozymes and microsatellites suggest that selection may be acting on some allozyme loci, specifically ACO-1, ACO-2, IDH-2 and MDH, which contributed most to the significant differentiation between samples. [source] SAFE biopsy: A validated method for large-scale staging of liver fibrosis in chronic hepatitis C,HEPATOLOGY, Issue 6 2009Giada Sebastiani The staging of liver fibrosis is pivotal for defining the prognosis and indications for therapy in hepatitis C. Although liver biopsy remains the gold standard, several noninvasive methods are under evaluation for clinical use. The aim of this study was to validate the recently described sequential algorithm for fibrosis evaluation (SAFE) biopsy, which detects significant fibrosis (,F2 by METAVIR) and cirrhosis (F4) by combining the AST-to-platelet ratio index and Fibrotest-Fibrosure, thereby limiting liver biopsy to cases not adequately classifiable by noninvasive markers. Hepatitis C virus (HCV) patients (2035) were enrolled in nine locations in Europe and the United States. The diagnostic accuracy of SAFE biopsy versus histology, which is the gold standard, was investigated. The reduction in the need for liver biopsies achieved with SAFE biopsy was also assessed. SAFE biopsy identified significant fibrosis with 90.1% accuracy (area under the receiver operating characteristic curve = 0.89; 95% confidence interval, 0.87-0.90) and reduced by 46.5% the number of liver biopsies needed. SAFE biopsy had 92.5% accuracy (area under the receiver operating characteristic curve = 0.92; 95% confidence interval, 0.89-0.94) for the detection of cirrhosis, obviating 81.5% of liver biopsies. A third algorithm identified significant fibrosis and cirrhosis simultaneously with high accuracy and a 36% reduction in the need for liver biopsy. The patient's age and body mass index influenced the performance of SAFE biopsy, which was improved with adjusted Fibrotest-Fibrosure cutoffs. Two hundred two cases (9.9%) had discordant results for significant fibrosis with SAFE biopsy versus histology, whereas 153 cases (7.5%) were discordant for cirrhosis detection; 71 of the former cases and 56 of the latter cases had a Fibroscan measurement within 2 months of histological evaluation. Fibroscan confirmed SAFE biopsy findings in 83.1% and 75%, respectively. Conclusion: SAFE biopsy is a rational and validated method for staging liver fibrosis in hepatitis C with a marked reduction in the need for liver biopsy. It is an attractive tool for large-scale screening of HCV carriers. (HEPATOLOGY 2009.) [source] Frequently discordant results from therapeutic drug monitoring for digoxin: clinical confusion for the prescriberINTERNAL MEDICINE JOURNAL, Issue 1 2010N. M. Rogers Abstract Background: Digoxin remains a commonly prescribed medication for the treatment of congestive cardiac failure or atrial tachyarrhythmias. Its utility is offset by its narrow therapeutic index requiring regular blood concentration monitoring. Recent evidence suggests that a lower therapeutic range (0.5,0.8 µg/L, or 0.6,1.0 nmol/L) is associated with reduced mortality in patients with congestive cardiac failure. Therapeutic drug monitoring for digoxin is carried out by immunoassays that are well established in routine clinical practice. Laboratories using different immunoassays may be involved in monitoring individual patients throughout the protracted course of therapy. These results should be concordant to ensure consistent dose individualization and optimum clinical management. We have investigated the discordance in digoxin measurements involving five different laboratories across the Adelaide metropolitan area. Methods: Aliquots from routine digoxin samples (n= 261) were analysed by accredited laboratories using commercially available immunoassays. Results: The results showed that 119 (46%) of 261 samples were so varied that a different clinical outcome was indicated when reviewed by the treating physician. The differences between the highest and lowest readings from any one sample were also substantial, with 45% of the measurements exceeding 0.3 µg/L. Conclusions: Our study shows the considerable variation in the routine monitoring of digoxin. This makes therapeutic drug monitoring difficult to interpret and complicates clinical management when treating physicians are endeavouring to avoid toxicity and optimize dosing. These results raise a significant concern for the quality of therapeutic drug monitoring of digoxin and have direct repercussions on patient care. [source] Comparison Insight Bone Measurements by Histomorphometry and ,CT,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005Daniel Chappard MD Abstract Morphometric analysis of 70 bone biopsies was done in parallel by ,CT and histomorphometry. ,CT provided higher results for trabecular thickness and separation because of the 3D shape of these anatomical objects. Introduction: Bone histomorphometry is used to explore the various metabolic bone diseases. The technique is done on microscopic 2D sections, and several methods have been proposed to extrapolate 2D measurements to the 3D dimension. X-ray ,CT is a recently developed imaging tool to appreciate 3D architecture. Recently the use of 2D histomorphometric measurements have been shown to provide discordant results compared with 3D values obtained directly. Material and Methods: Seventy human bone biopsies were removed from patients presenting with metabolic bone diseases. Complete bone biopsies were examined by ,CT. Bone volume (BV/TV), Tb.Th, and Tb.Sp were measured on the 3D models. Tb.Th and Tb.Sp were measured by a method based on the sphere algorithm. In addition, six images were resliced and transferred to an image analyzer: bone volume and trabecular characteristics were measured after thresholding of the images. Bone cores were embedded undecalcified; histological sections were prepared and measured by routine histomorphometric methods providing another set of values for bone volume and trabecular characteristics. Comparison between the different methods was done by using regression analysis, Bland-Altman, Passing-Bablock, and Mountain plots. Results: Correlations between all parameters were highly significant, but ,CT overestimated bone volume. The osteoid volume had no influence in this series. Overestimation may have been caused by a double threshold used in ,CT, giving trabecular boundaries less well defined than on histological sections. Correlations between Tb.Th and Tb.Sp values obtained by 3D or 2D measurements were lower, and 3D analysis always overestimated thickness by ,50%. These increases could be attributed to the 3D shape of the object because the number of nodes and the size of the marrow cavities were correlated with 3D values. Conclusion: In clinical practice, ,CT seems to be an interesting method providing reliable morphometric results in less time than conventional histomorphometry. The correlation coefficient is not sufficient to study the agreement between techniques in histomorphometry. The architectural descriptors are influenced by the algorithms used in 3D. [source] Do intrinsic factor antibodies assays provide univocal answers in Biermer's disease?JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2008Jean-Benoīt Corcuff Abstract The objective of the study is to evaluate the concordance of four assays for antibodies against intrinsic factor (IF-Ab). Sixty-two sera were tested with one competitive automated and three manual noncompetitive assays. Thirty-five percent patients had discordant results with at least one of the four assays. However, any method uncovered patients with proven Biermer's disease missed by the others assays. The observed discordance partly explains the poor sensitivity of IF-Ab in studies using a single assay. J. Clin. Lab. Anal. 22:337,339, 2008. © 2008 Wiley-Liss, Inc. [source] Extracranial and intracranial vertebral artery dissection: Long-term clinical and duplex sonographic follow-upJOURNAL OF CLINICAL ULTRASOUND, Issue 8 2008Tiemo Wessels MD Abstract Purpose. To determine the value of color Doppler sonography (CDUS) in the diagnosis and follow-up of patients with extracranial and intracranial vertebral artery (VA) dissection. Method. Thirty-three patients aged 42 ± 12 years with 40 VADS confirmed via digital subtraction angiography (DSA) (n = 37) and magnetic resonance angiography (MRA) (n = 3) were included in the study. All patients were investigated with extracranial CDUS and transcranial CDUS (TCCDUS) over a mean ± SD follow-up period of 42 ± 24 months and occurrence of new ischemic symptoms was assessed. Sonographic results were compared with initial and follow-up angiographic results. Results. At presentation, 24/33 (73%) patients had suffered an ischemic stroke, 5/33 (15%) had a transient ischemic attack (TIA), and 4/33 (12%) were asymptomatic. Two patients had a recurrent vertebrobasilar TIA; there was no recurrent stroke. The initial DSA findings consisted of 14 stenoses, 20 tapered occlusions, and 6 pseudoaneurysms. During follow-up, 63% of the vessels recanalized. Sonographic findings were consistent with angiographic findings in 80% at the initial examination and in 86% during follow-up. The main reason for discordant results was the failure of CDUS to detect pseudoaneurysms. No recurrence occurred in the vertebral arteries (VA), but 1 patient had an asymptomatic carotid artery dissection during follow-up. Conclusion. Recurrent TIA or stroke after VAD appears to be extremely rare, independent of recanalization or persistent occlusion of the affected artery. CDUS and TCCDUS provide reliable follow-up of VAD in all patients presenting with stenosis or occlusion, but do not allow for detection of pseudoaneurysms of the VA. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008 [source] Preoperative localization of parathyroid adenoma with sonography and 99mTc-sestamibi scintigraphy in primary hyperparathyroidismJOURNAL OF CLINICAL ULTRASOUND, Issue 4 2007Ilaria Grosso MD Abstract Purpose. To evaluate the sensitivity, specificity, and usefulness of dual-phase 99mTc-Sestamibi scintigraphy (SS) and sonography (US) of the neck, alone and in combination, as noninvasive adenoma localizing procedures in patients with primary hyperparathyroidism prior to parathyroidectomy. Methods. We retrospectively analyzed the charts of 79 patients with parathyroid (PT) adenomas and confirmed diagnosis of hyperparathyroidism who were evaluated with SS and US prior to successful parathyroidectomy. Results. Ninety-three adenomas were removed during bilateral neck exploration. SS alone showed a sensitivity of 76% and a specificity of 79% compared with 89% and 75%, respectively, for US performed after SS on the same day. Combination of the 2 procedures yielded a sensitivity of 89% and a specificity of 90%, with 22% discordant results. The differences in sensitivity and specificity between the 2 techniques alone or in combination were not statistically significant. Conclusions. No benefit was gained from using both SS and US for the preoperative localization of PT adenomas in patients with primary hyperparathyroidism. Each technique can be negatively affected by thyroid enlargment and nodularity. US, when performed by a skilled operator, is a reliable tool for PT adenoma localization. If the US findings are inconclusive, SS should be used. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007 [source] Evaluating the use of plasma hematocrit samples to detect ketones utilizing urine dipstick colorimetric methodology in diabetic dogs and catsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 1 2003Mark A. Brady DVM Abstract Objective: To determine whether plasma from a heparinized hematocrit tube placed on a urine dipstick would accurately reflect (positive or negative) urine ketone results in diabetic dogs and cats. Design: Prospective study, 37 dogs and 43 cats, with a known history of diabetes or hyperglycemia, glucosuria, and symptoms of undiagnosed diabetes mellitus were tested. Setting: Veterinary Referral Hospital. Animals: Client owned dogs and cats. Interventions: None. Measurement and main results: Heparinized plasma and urine ketone results were recorded using urine reagent strips. Plasma dipstick results were compared to urine dipstick results as the standard. Results were recorded based on the color chart provided by the manufacturer. Two individuals were responsible for verifying the results of the colorimetric test. Test efficiency was 97% (sensitivity = 96%, specificity = 100%) for the canine population, 93% (sensitivity = 100%, specificity = 83%) for the feline population, and 95% (sensitivity = 98%, specificity = 91%) for the total population. Four of 80 animals were found to have discordant results (1 dog and 3 cats). Conclusion: Plasma from heparinized hematocrit tubes is clinically useful for detecting the presence or absence of ketonuria, and therefore ketosis, in diabetic dogs and cats using urine dipstick colorimetric methodology. [source] Gene expression microarray analysis and genome databases facilitate the characterization of a chromosome 22 derived homogenously staining regionMOLECULAR CARCINOGENESIS, Issue 1 2004Suzanna L. Arcand Abstract Karyotype and fluorescence in situ hybridization (FISH) analyses previously identified a homogenously staining region (HSR) derived from chromosome 22 in OV90, an epithelial ovarian cancer (EOC) cell line. Affymetrix® expression microarrays in combination with the UniGene and Human Genome Browser databases were used to identify the candidate genes comprising the amplicon of the HSR, based on comparison of expression profiles of OV90, EOC cell lines lacking HSRs and primary cultures of normal ovarian surface epithelial (NOSE) cells. A group of probe sets displaying a minimum 3-fold overexpression with a high reliability score (P-call) in OV90 were identified which represented genes that mapped within a 1,2 Mb interval on chromosome 22. A large number of probe sets, some of which represent the same genes, displayed no evidence of overexpression and/or low reliability scores (A-call). An investigation of the probe set sequences with the Affymetrix® and Sanger Institute Chromosome 22 Group databases revealed that some of the probe sets displaying discordant results for the same gene were complementary to intronic sequences and/or the antisense strand. Microarray results were validated by RT-PCR. Genomic analysis suggests that the HSR was derived from the amplification of a 1.1 Mb interval defined by the chromosomal map positions of ZNF74 and Hs.372662, at 22q11.21. The deduced amplicon is derived from a complex region of chromosome 22 that harbors low-copy repeats (LCRs). The amplicon contains 18 genes as likely targets for gene amplification. This study illustrates that large-scale expression microarray analysis in combination with genome databases is sufficient for deducing target genes associated with amplicons and stresses the importance of investigating probe set design before engaging in validation studies. © 2004 Wiley-Liss, Inc. [source] Population genetic structure, gene flow and sex-biased dispersal in frillneck lizards (Chlamydosaurus kingii)MOLECULAR ECOLOGY, Issue 15 2008BEATA UJVARI Abstract By using both mitochondrial and nuclear multiloci markers, we explored population genetic structure, gene flow and sex-specific dispersal of frillneck lizards (Chlamydosaurus kingii) sampled at three locations, separated by 10 to 50 km, in a homogenous savannah woodland in tropical Australia. Apart from a recombinant lizard, the mitochondrial analyses revealed two nonoverlapping haplotypes/populations, while the nuclear markers showed that the frillneck lizards represented three separate clusters/populations. Due to the small population size of the mtDNA, fixation may occur via founder effects and/or drift. We therefore suggest that either of these two processes, or a combination of the two, are the most likely causes of the discordant results obtained from the mitochondrial and the nuclear markers. In contrast to the nonoverlapping mitochondrial haplotypes, in 12 out of 74 lizards, mixed nuclear genotypes were observed, hence revealing a limited nuclear gene flow. Although gene flow should ultimately result in a blending of the populations, we propose that the distinct nuclear population structure is maintained by frequent fires resulting in local bottlenecks, and concomitant spatial separation of the frillneck lizard populations. Limited mark,recapture data and the difference in distribution of the mitochondrial and nuclear markers suggest that the mixed nuclear genotypes were caused by juvenile male-biased dispersal. [source] Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Ashkan Emadi The objective of this study is to systematically review methods for detecting Factor V Leiden or prothrombin G20210A. English-language literature from MEDLINE®, EMBASE®, The Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo©, 2000-December 2008. Studies assessed methods for detection of these mutations in at least 10 human blood samples and reported concordance, discordance, or reproducibility. Two investigators abstracted data on the sample selection criteria, test operators, DNA extraction, experimental test, reference standard, commercial instruments, concordance rates, explanation of any discordance, and whether discordance resolved after repetition. We assessed strength of the evidence using the GRADE criteria. We reviewed 7,777 titles and included 66 articles. The majority of the reviewed studies used PCR-RFLP or AS-PCR as the reference standard. The studies demonstrated that commercially available and precommercial tests have high analytic validity with all having greater than 99% concordance with the reference standard. With a few exceptions, discordance resolved with repetition of the test, suggesting operator or administrative errors were responsible for the discordant results. In the quality assurance studies, greater than 98% of laboratories demonstrated high, even perfect, accuracy when asked to diagnose a sample with a known mutation. The majority of errors came from a limited number of laboratories. Although not all methods may be accurate, there is high-grade evidence that genetic tests for the detection of FVL and prothrombin G20210A have excellent analytic validity. There is high-grade evidence that most, but not all, clinical laboratories test for FVL and prothrombin G20210A accurately. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Rapid prenatal diagnosis of common trisomies: discordant results between QF-PCR analysis and karyotype analysis on long-term culture for a case of trisomy 18 detected in CVSPRENATAL DIAGNOSIS, Issue 12 2006S. K. Allen Abstract Objectives QF-PCR analysis can be used as a rapid test to diagnose primary trisomy in prenatal samples. Mosaicism in CVS detected by QF-PCR has previously been reported; however, no case has so far been reported in which the QF-PCR result was completely discrepant to that of the karyotype analysis from a long-term culture. Methods A CVS, referred because of a high serum screening risk of 1:10 for Down Syndrome and 1:110 for Edwards Syndrome, was tested by QF-PCR analysis and chromosome analysis of cultured cells. Subsequent analyses were carried out on a follow-up amniotic fluid sample and foetal tissue samples. Results Conflicting results were obtained between QF-PCR analysis on two independent fronds from the chorionic villi and chromosome analysis on cultured CVS. Cytogenetic and molecular analysis on a subsequent amniotic fluid sample indicated trisomy 18 with no evidence of mosaicism. Analysis of follow-up tissue confirmed trisomy in a foetal skin sample and mosaicism for trisomy 18 in four placental sites tested. Conclusion We report here an apparently normal CVS QF-PCR result that was completely discrepant with the trisomy 18 positive karyotype result on long-term culture. This has important implications regarding our current testing protocol. Copyright © 2006 John Wiley & Sons, Ltd. [source] Scanning for chorionicity: comparison between sonographers and perinatologistsPRENATAL DIAGNOSIS, Issue 9 2005Boaz Weisz Abstract Objective In most prenatal settings, twin pregnancies are initially evaluated by sonographers. Pregnancies diagnosed as monochorionic are subsequently referred to perinatologists or specialists in fetal medicine for the confirmation of chorionicity. In order to assess this screening strategy, we have compared the diagnosis of chorionicity made by the sonographers in the ultrasound department with the diagnosis done in the fetal medicine unit. Methods A cohort of women presenting with twin pregnancy and booked for prenatal care at University College London Hospitals over a 4-year period were investigated prospectively. All women were scanned at their initial visit at 11,14 weeks in the ultrasound department (US), and were subsequently referred to the Fetal Medicine Unit (FMU) for a second ultrasound evaluation. Ultrasound data were compared and diagnosis of chorionicity was confirmed by examination of the inter-twin membranes after delivery. Results Chorionicity was determined in 172 twin cases by the two different departments. The overall rate of concordant chorionicity determination between both units was 90.1%. The rate of discordant results in dichorionic pregnancies was extremely small, 1 in 119 pregnancies (0.8%). The rate of discordant results for monochorionic diamniotic pregnancies was 5.5%. Monoamniotic pregnancies were over-diagnosed by the US technicians. Discussion These results demonstrate that DC/DA chorionicity is accurately determined by sonographers at less than 14 weeks. In our opinion, it is both efficient and safe to rely on the diagnosis of the sonographers in DC/DA pregnancies in early pregnancy. In such pregnancies, a decision can be made either not to refer these patients for further evaluation of chorionicity by the fetal medicine team or to postpone the referral to after 14 weeks. Copyright © 2005 John Wiley & Sons, Ltd. [source] The relationship between women's subjective and physiological sexual arousalPSYCHOPHYSIOLOGY, Issue 1 2005Alessandra H. Rellini Abstract Previous literature presents discordant results on the relationship between physiological and subjective sexual arousal in women. In this study, the use of hierarchical linear modeling (HLM) revealed a significant concordance between continuous measures of physiological and subjective sexual arousal as assessed during exposure to erotic stimuli in a laboratory setting. We propose that past studies that have found little or no association between the two measures may have been in part limited by the methodology and statistical analyses employed. [source] The new ATS/ERS guidelines for assessing the spirometric severity of restrictive lung disease differ from previous standardsRESPIROLOGY, Issue 5 2007Ashutosh N. AGGARWAL Background and objectives: The ATS/ERS Task Force on Lung Function Testing recently proposed guidelines for the interpretation of pulmonary function tests and suggested that a reduction in FEV1 be used for categorizing both obstructive and restrictive abnormalities. This changes the severity stratification algorithm of restrictive patterns diagnosed by spirometry, that are currently categorized based on reduction in VC. This study examined the level of agreement between these two categorization schemes. Methods: Spirometry records of 2527 adult patients evaluated over 1 year were retrieved; 361 of these patients showed a restrictive pattern. Severity of airway restriction was separately assessed in these patients using the indicative schemes provided in the new ATS/ERS and the earlier ATS guidelines. Results: There were 212 (58.7%) patients with a restrictive pattern who had identical severity categorization using both guidelines. In most instances of discordance, the severity categorization differed only by a single stratum. Of 149 discordant results, 91 (60.1%) were placed in a better category, and 58 (39.9%) in a worse category, when using the new ATS/ERS recommendations. Overall weighted kappa estimate for agreement between the two schemes of categorization was 0.649. Conclusion: Based on spirometry results, the level of severity of restriction cannot be described interchangeably between the old and new guidelines for all patients. The new guidelines tend to give lower severity scores for restrictive lung diseases in up to 25% of patients. [source] Discordant performance of assays for free and total prostate-specific antigen in relation to the early detection of prostate cancerBJU INTERNATIONAL, Issue 6 2001B.G. Blijenberg Objective To assess the value of applying rigid threshold values in interpreting prostate specific antigen (PSA) results, by selecting and comparing five current methods for measuring free and total PSA. Materials and methods Samples taken from an ongoing screening study for prostate cancer (total PSA by Tandem-E assay, 17,334 participants; biopsy criterion a PSA of 3.0 µg/L, 4,464 men) from men with a total PSA of 1.0,6.0 µg/L were measured for free and total PSA using the Access, Immulite, Elecsys and Prostatus analysis kits, in two patient groups, i.e. with prostate cancer or no evidence of disease. Results Both patient groups had equal means for total PSA but not for free PSA. In all, 360 samples from men with cancer and 96 from men with no evidence of disease were analysed. All methods applied to both groups deviated statistically significantly from the Tandem-E result for total PSA, except for the Access kit. There was a close correlation among all the methods (correlation coefficients of 0.89,0.97). There were very discordant results for the combination of the Tandem-E vs Prostatus (8% difference), representing 315 participants at a threshold of 3.0 µg/L. For free PSA (free/total PSA) the situation was worse, with extreme differences of 32% and 36% for both patient groups (Elecsys vs Access). Conclusions Depending on the threshold value applied as an indication for biopsy, when using the total PSA alone or combined with the free/total PSA, care is needed in interpreting patient groups because of the discordance among PSA assays. [source] Does subclinical hypercortisolism adversely affect the bone mineral density of patients with adrenal incidentalomas?CLINICAL ENDOCRINOLOGY, Issue 1 2003D. Hadjidakis Summary objective Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. patients and measurements,Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0·5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of > 70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2,L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method. results Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm2: 0·72 ± 0·08 vs. 0·79 ± 0·09; Z -score: ,0·20 ± 0·82 vs. +0·43 ± 0·94, P < 0·05) and trochanter (BMD g/cm2: 0·60 ± 0·09 vs. 0·69 ± 0·10; Z -score: ,0·32 ± 1·0 vs. +0·30 ± 1·05, P < 0·01). BMD measurements of the Ward's triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm2: 0·60 ± 0·10 vs. 0·68 ± 0·13, P = 0·06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm2: 0·888 ± 0·13 vs. 0·90 ± 0·16, P = 0·78; z-score: +0·50 ± 1·16 vs. +0·11 ± 1·5, P = 0·36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18·6 ± 8·6 vs. 26·2 ± 8·1 ng/ml, P < 0·01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 ± 15·6 vs. 41·2 ± 14·8 pg/ml, P = 0·72). conclusions In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical,trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients. [source] | |||||||||||||