Urinary FOXP3 messenger RNA and renal-allograft rejection.
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Acute Disease↗
Biomedical subjects
James C Boyd
Publications and source records attributed to James C Boyd.
The use of urinary dipstick tests to exclude urinary tract infection: a systematic review of the literature.
Several systematic reviews have examined the use of dipstick tests to diagnose or rule in urinary tract infection (UTI). We examined the evidence relating to the use of urine leukocyte esterase and nitrite tests in adults to exclude or rule out UTI. A search of the literature from 1966 to 2003 revealed 30 studies as containing relevant and suitable information and 23 of these, which used a cut-off of 108 colony-forming units per liter, were combined in a meta-analysis. The leukocyte esterase or nitrite test combination, with one or the other test positive, was used in 14 studies, showed the highest sensitivity and the lowest negative likelihood ratio. While there was significant heterogeneity between the studies, 7 of 14 demonstrated significant decreases in pretest to posttest probability with a pooled posttest probability of 5% for the negative result. In certain circumstances, there is evidence for the use of urinalysis as a rule-out test for UTI.
Carboxylic Ester Hydrolases↗
Imported platelets demonstrate decreased pH and glucose by reagent strip testing when compared to locally derived platelets.
The most common infectious risk from blood transfusion in the United States is bacterial contamination of platelet components. Although detection of bacterially contaminated platelet components is best achieved with a culture system, AABB standards permit alternatives including the use of staining methods or reagent strips. In this study, 13,216 consecutive platelet components were screened using reagent strips for evidence of the presence of bacteria. Testing was performed immediately prior to release of the platelet components for transfusion; 10,836 were collected locally and 2,380 were imported from other blood banks. A mix of whole-blood-derived and apheresis products was included. If either the glucose concentration was <250 mg/ml or the pH was <7.0, the platelet component was quarantined and a specimen was obtained for Gram's stain and culture. Every transfused platelet component that was associated with a reported transfusion reaction was also tested by Gram's stain and culture. Overall, 1.47% of imported platelet components were reactive while only 0.12% of locally collected platelets were reactive. Of 48 reactive platelet components, 44 were tested by Gram's stain and culture. None was found to be bacterially contaminated. In summary, imported platelet components were significantly more likely to be falsely reactive by reagent strip screening as compared to locally prepared platelet components.
Bacteria↗
Use of protein:creatinine ratio measurements on random urine samples for prediction of significant proteinuria: a systematic review.
BACKGROUND: Proteinuria is recognized as an independent risk factor for cardiovascular and renal disease and as a predictor of end organ damage. The reference test, a 24-h urine protein estimation, is known to be unreliable. A random urine protein:creatinine ratio has been shown to correlate with a 24-h estimation, but it is not clear whether it can be used to reliably predict the presence of significant proteinuria. METHODS: We performed a systematic review of the literature on measurement of the protein:creatinine ratio on a random urine compared with the respective 24-h protein excretion. Likelihood ratios were used to determine the ability of a random urine protein:creatinine ratio to predict the presence or absence of proteinuria. RESULTS: Data were extracted from 16 studies investigating proteinuria in several settings; patient groups studied were primarily those with preeclampsia or renal disease. Sensitivities and specificities for the tests ranged between 69% and 96% and 41% and 97%, respectively, whereas the positive and negative predictive values ranged between 46% and 95% and 45% and 98%, respectively. The positive likelihood ratios ranged between 1.8 and 16.5, and the negative likelihood ratios between 0.06 and 0.35. The cumulative negative likelihood ratio for 10 studies on proteinuria in preeclampsia was 0.14 (95% confidence interval, 0.09-0.24). CONCLUSION: The protein:creatinine ratio on a random urine specimen provides evidence to "rule out" the presence of significant proteinuria as defined by a 24-h urine excretion measurement.
Creatinine↗
Evaluation of analytical methods and workflow performance of the Architect ci8200 integrated serum/plasma analyzer system.
BACKGROUND: The Architect ci8200 is an integrated serum analyzer for photometric, electrochemical and immunological assays. Several assays of each category and the workflow performance of the system were compared with established laboratory procedures in two laboratories. METHODS: Measurements were compared with the ELECSYS 2010 (Roche Diagnostics) for CEA, PSA, FPSA, AFP, folate, vitamin B12, with the CENTAUR (Bayer) for TSH, T4, FT4, FSH and Estradiol, with the LIAISON (DiaSorin) for TSH, FT4 and FT3, with the Behring Nephelometer BN II (Dade-Behring) for ferritin, and with the INTEGRA 800 (Roche Diagnostics), and the AU640 (Olympus) for clinical chemistry assays. Workflow studies were performed to compare times of analysis required for defined analytical workloads. RESULTS: The coefficients of variation (CVs) for within-run imprecision were between 3% and 6% for CEA, PSA, FPSA, AFP and ferritin, and between 3% and 11% for TSH, FT4, FT3, folate and vitamin B12. The CVs for day-to-day imprecision for immunoassays were between 3% and 10%, except for vitamin B12 (CVs 11-13%) and FT4 (CV 10% -13%). For clinical chemistry tests corresponding CVs for within-run imprecision were < 1%, except for HDL, triglyceride, creatinine, ALT, LD and lipase (CVs<2%) and bicarbonate (CV 3%-6%) and magnesium (CV < 3%). The CVs for day-to-day imprecision for clinical chemistry tests were < 1%, except for sodium, CO(2), magnesium, phosphorus, glucose, uric acid, HDL, triglyceride, ALT, AST CK, lipase with CVs < 6% and for CO(2)<11%. Dilutional linearity testing of seven immunoassays and five clinical chemistry analytes resulted in recovery rates of 90-110%. Correlation studies with 15 immunoassays and 25 clinical chemistry tests showed acceptable agreements with established methods. Work flow analyses demonstrated a net gain in time of analysis up to 109 min depending on the size of the sample batch analyzed with the Architect ci8200 as the main analyzer as compared to the currently installed routine laboratory equipment. Median turn-around times were 7 and 30 min for chemistry assays and immunoassays, respectively, when ordered as STAT analyses, and 18 min when chemistry assays were ordered as routine determinations. CONCLUSIONS: Assays on the Architect ci8200 performed well, fulfilling quality control requirements as defined for instance by German quality control guidelines (RiliBAK). Method comparisons showed acceptable agreements with established assays. Workflow studies using the Architect ci8200 documented shorter times of analyses as compared with the conventionally established laboratory routine demonstrating the potential of integrated chemistry/immunoassay analyzers to provide faster and more efficient performance.
Bicarbonates↗
Partitioning of nongaussian-distributed biochemical reference data into subgroups.
BACKGROUND: The aim of this study was to develop new methods for partitioning biochemical reference data, covering in particular nongaussian distributions. METHODS: We recently proposed partitioning criteria for gaussian distributions. These criteria relate to proportions of the subgroups outside each of the reference limits of the combined distribution (proportion criteria) and to distances between the subgroup distributions as correlates of these proportions (distance criteria). However, distance criteria do not seem to be ideal for nongaussian distributions because a generally valid relationship between proportions and distances cannot be established for these. RESULTS: Proportion criteria appear preferable to distance criteria for two additional reasons: (a) The prevalences of the subgroup populations may have a considerable effect on stratification, but these are hard to account for by using distance criteria. Two methods to handle prevalences are described, the root method and the multiplication method. (b) Tied reference values, another complication of the partitioning problem, could also be hard to take care of using distance criteria. Some solutions to the problems caused by tied reference values are suggested. CONCLUSIONS: Partitioning of biochemical reference data should preferably be based on proportion criteria; this is particularly true for nongaussian distributions. Both of the described complications of the partitioning problem, the prevalences of the subgroups and tied reference values, are hard to deal with using distance criteria, but the proposed methods make it possible to account for them when proportion criteria are applied.
Clinical Laboratory Techniques↗
Reference regions of two or more dimensions.
Despite being proposed over 30 years ago, the multivariate reference region (MRR) remains an interpretive tool with uncertain value in clinical practice. This paper reviews the mathematical theory of the MRR, presents topics in the clinical application of MRRs, and examines the advantages and disadvantages of MRRs. Finally, some thoughts are offered regarding future directions for work in this field.
Analysis of Variance↗
Why patients choose prostatectomy or brachytherapy for localized prostate cancer: results of a descriptive survey.
OBJECTIVES: Limited data exist as to the reasons patients have for deciding among potentially curative treatment choices in clinically localized prostate cancer. Therefore, we carried out a descriptive pilot study to determine such motivations, sources of information, and other variables that influence how such patients choose between radical prostatectomy (RP) and brachytherapy (BT). METHODS: Three hundred fifty-one men with clinically localized Stage T1c-T3 adenocarcinoma of the prostate were treated by RP or palladium-103 BT, either alone (BTM) or in combination with external radiotherapy (BTC). On June 1, 2000, patients were mailed a questionnaire, and cross-sectional analysis of the returned questionnaires was carried out. RESULTS: Of 351 men, 262 (74.6%) responded to the survey; 65% chose treatment on the basis of evidence or an impression that it was the best procedure to cure their cancer. The possible side effects were also an important motivation for choosing a procedure. BTC patients listed the risk of urinary incontinence as the most disturbing and both RP and BTM patients listed sexual dysfunction. The most common unpleasant surprise for all treatment groups was bowel or bladder dysfunction. The most common pleasant surprise was a quick recovery. Urologists were the most important source of information and the major factor influencing the treatment decision. Surprisingly, spouses and fellow patients were relatively minor influences in this process. CONCLUSIONS: The results from this pilot study indicate that other factors beyond "cancer cure" are very important patient treatment decisions. In addition, by examining post-treatment "surprises," our data will allow the development of improved educational approaches to aid decision making.
Adenocarcinoma↗
Massive caffeine overdose requiring vasopressin infusion and hemodialysis.
INTRODUCTION: Massive caffeine overdose is associated with life-threatening hemodynamic complications that present challenges for clinicians. We describe the highest-reported serum concentration of caffeine in a patient who survived and discuss the first-reported use of vasopressin and hemodialysis in a caffeine-poisoned patient. CASE REPORT: A 41-yr-old woman presented 3 h after ingesting approximately 50 g of caffeine. She subsequently underwent cardiopulmonary resuscitation and received multiple medications in an attempt to raise her blood pressure and control her heart rate without success. Vasopressin infusion increased her blood pressure to the point where hemodialysis could be performed. Despite ensuing multisystem organ failure, she survived and has made a complete recovery. CONCLUSION: Hemodialysis and vasopressin infusions may be of benefit in the management of caffeine-intoxicated patients who fail to respond to standard therapies.
Adult↗
Comparison of diagnostic accuracies in outpatients and hospitalized patients of D-dimer testing for the evaluation of suspected pulmonary embolism.
BACKGROUND: The ability of various D-dimer assays to exclude the diagnosis of thromboembolic diseases is controversial. We examined the diagnostic accuracy of two D-dimer methods in hospitalized patients and outpatients. METHODS: We studied consecutive patients for whom D-dimer testing was ordered for investigation of suspected pulmonary embolism. We measured D-dimer by an ELISA (VIDAS D-dimer) and an enhanced microlatex immunoassay method (Diagnostica Stago STA Liatest D-di). Patient diagnoses were based on imaging studies or, when these were not performed, on follow-up by review of medical records 3 months later. RESULTS: We examined 233 hospitalized patients and 234 outpatients with a mean age of 58 years (range, 1-92 years) and a female-to-male ratio of 1.4 to 1. Thromboembolism was present in 8% of outpatients and 12% of hospitalized patients. In outpatients, the negative predictive values were 98% [95% confidence interval (CI), 93-100%] and 99% (94-100%) for the microlatex and ELISA methods, respectively, at the recommended cutoffs. Areas under the ROC curves were similar for the two methods [0.77 (95% CI, 0.67-0.87) and 0.81 (0.73-0.89), respectively]. By contrast, in hospitalized patients, the confidence intervals for the areas under the ROC curves included 0.5 [0.60 (95% CI, 0.50-0.71) and 0.56 (0.44-0.67)]. CONCLUSIONS: For hospitalized patients, in contrast to outpatients, the diagnostic accuracy of D-dimer testing for pulmonary embolism is poor in a tertiary care setting, presumably reflecting thrombosis and comorbidities, other than pulmonary embolism, that increase the D-dimer concentrations in these patients. The patient population studied appears more important than assay method in studies of the diagnostic accuracy of D-dimer testing.
Adolescent↗
Gleason scores of prostate biopsy and radical prostatectomy specimens over the past 10 years: is there evidence for systematic upgrading?
BACKGROUND: With the advent of the prostate specific antigen (PSA) assay, an increased detection rate of prostate carcinoma has ensued. This has been associated with a downward stage migration. In contrast, grade has shifted heavily toward moderate differentiation. The authors sought to test the hypothesis that such changes in grade in part may be because of trends among pathologists to upgrade similar specimens over time. METHODS: Two expert genitourinary pathologists regraded 23 prostate biopsies and 15 radical prostatectomy specimens during a 3-year period (1989-1991). Each pathologist then regraded 32 prostate biopsies and 15 radical prostatectomies from 1998 to 2000. For both time periods, each pathologist regraded only specimens that they personally had graded initially. All specimens were scored using the Gleason system, the predominant system used in describing prostate carcinoma grade. In evaluating original and regraded scores, the authors classified score changes between less than or equal to 6 and greater than or equal to 7 or between 7 and greater than or equal to 8 as significant because such changes have a high probability of altering clinical management. The results were analyzed using the two-tailed Fisher exact test. RESULTS: Of 23 prostate biopsies from 1989 to 1991, 10 of 23 (44%) had a clinically significant Gleason score change when regraded, whereas 2 of 15 (13%) radical prostatectomy specimens from the same period had a clinically significant Gleason score change. A significant change in the distribution of biopsy Gleason scores on regrading was observed (P < 0.04). In comparison, when the prostate biopsies from 1998-2000 were regraded, 10 of 32 (31%) had a clinically significant grade change. Radical prostatectomy specimens from the same period revealed 3 of 15 (20%) with a clinically significant grade change. After regrading the biopsies from 1989-1991, 8 of 23 (35%) of were upgraded, whereas 2 of 23 (9%) were downgraded. In comparison, of the biopsies with significant changes from 1998 to 2000, 3 of 32 (9%) were upgraded, whereas 7 of 32 (22%) were downgraded. Of the radical prostatectomy specimens with significant change, only 2 of 15 from each period were upgraded. Significant upgrading (P < 0.005) occurred only in the biopsy specimens from 1989 to 1991. CONCLUSIONS: The authors' data suggest that rates of upgrading and downgrading of biopsy specimens differ between the 1989-1991 cases and the 1998-2000 cases, with the 1989-1991 samples exhibiting a significant change toward higher grades. Although not excluding the possibility of a change in the biology of prostate carcinoma over time, these findings suggest that the apparent trend toward higher biopsy grades in part may be because of how pathologists interpret these specimens today as compared with 10 years ago. Therefore, outcome studies including a biopsy Gleason score from older specimens as a risk variable have a significant chance of being vulnerable to this phenomenon. Based on the authors' data, all such specimens should undergo rereview.
Biopsy, Needle↗
Perioperative costs and charges of prostate brachytherapy and prostatectomy.
OBJECTIVES: To compare the costs and charges incurred for transrectal ultrasound-guided brachytherapy (USBT) and radical prostatectomy (RP) at a single institution. METHODS: From February 1998 to March 1999, 66 consecutive patients underwent potentially curative therapy for clinically localized prostate cancer. Thirty-seven were treated by USBT using palladium-103 brachytherapy and 29 by RP. Hospital costs and charges and professional fees were obtained for a 2-month period beginning 1 month before RP or USBT and compared between the two procedures. RESULTS: The mean total charges for USBT ($26,320) and RP ($22,660) were not significantly different. Compared with RP, USBT incurred significantly lower operating room time cost ($628 for USBT versus $2093 for RP, P <0.05). The average cost of seeds for USBT was $6184, which resulted in higher technical costs for USBT than for RP ($12,209 versus $7746, P <0.05). This was offset by lower professional fees for USBT ($7575 versus $9531). The ratio of charge to cost was lower for USBT than for RP (2.2 versus 3.0). CONCLUSIONS: The total charges associated with brachytherapy appear similar to those associated with RP, although RP had relatively lower technical costs. Without a clear cost advantage of USBT over RP, the choice of therapy should continue to be primarily influenced by tumor characteristics, treatment efficacy, and patient preference.
Adenocarcinoma↗
Localization of the neuronal class III beta-tubulin in oligodendrogliomas: comparison with Ki-67 proliferative index and 1p/19q status.
The class III beta-tubulin isotype (betaIII) is widely regarded as a neuronal marker in development and neoplasia. Whereas the expression of betaIII in neuronal/neuroblastic tumors is differentiation-dependent, the aberrant expression of this cytoskeletal protein in astrocytomas is associated with an ascending gradient of malignancy. To test the generality of this observation we have compared the immunoreactivity (IR) profiles of the betaIII isotype with the Ki-67 nuclear antigen proliferative index in 41 archival, surgically excised oligodendrogliomas (32 classical [WHO grade II] and 9 anaplastic [WHO grade III]). Seventeen of 41 tumors were examined by quantitative microsatellite analysis for loss of 1p and/or 19q. Minimal deletion regions were defined on 1p (D1S468, D1S214) and 19q (D19S408, D19S867). Three of 10 classical oligodendrogliomas had combined 1p/19q loss, while 2 exhibited loss of either 1p or 19q. Three of 7 anaplastic tumors had combined 1p/19q loss. BetaIII IR was present in all tumors, but was significantly greater in the anaplastic (median labeling index [MLI] 61%, interquartile range [IQR] 55%-64%) as compared with the classical variants (MLI, 19%, IQR, 11-36%) (p < 0.0001). A highly significant relationship was found to exist between betaIII and Ki-67 LIs (betaIII, p < 0.0001 and Ki-67, p < 0.0001. r = 0.809). BetaIII localization delineated hitherto understated unipolar or bipolar tumor phenotypes with growth cones and leading cell processes resembling migrating oligodendrocyte progenitor cells. Codistribution of betaIII and GFAP IR was present in "gliofibrillary" tumor areas. Synaptophysin IR was detected in rare tumor cells (mean LI, 0.7%), and only in 4/41 samples (10%), denoting a lack of relationship between betaIII and synaptophysin expression. No significant differences in betaIII LIs were observed in tumors with 1p and/or 19q loss as compared to those with 1p/19q intact status. Increased betaIII IR in oligodendrogliomas is associated with an ascending degree of malignancy and thus is a potentially useful tumor marker. However, the significance of high betaIII LIs in low-grade oligodendrogliomas with respect to prognostic and predictive value requires further evaluation. Class III beta-tubulin expression in oligodendrogliomas should not be construed as a priori evidence of divergent neuronal differentiation.
Biomarkers, Tumor↗
Objective criteria for partitioning Gaussian-distributed reference values into subgroups.
BACKGROUND: The aim of this study was to develop new and useful criteria for partitioning reference values into subgroups applicable to gaussian distributions and to distributions that can be transformed to gaussian distributions. METHODS: The proposed criteria relate to percentages of the subgroups outside each of the reference limits of the combined distribution. Critical values suggested as partitioning criteria for these percentages were derived from analytical bias quality specifications for using common reference intervals throughout a geographic area. As alternative partitioning criteria to the actual percentages, these were transformed mathematically to critical distances between the reference limits of the subgroup distributions, to be applied to each pair of reference limits, the upper and the lower, at a time. The new criteria were tested using data on various plasma proteins collected from approximately 500 reference individuals, and the outcomes were compared with those given by the currently widely applied and recommended partitioning model of Harris and Boyd, the "Harris-Boyd model". RESULTS: We suggest 4.1% as the critical minimum percentage outside that would justify partitioning into subgroups, and 3.2% as the critical maximum percentage outside that would justify combining them. Percentages between these two values should be classified as marginal, implying that nonstatistical considerations are required to make the final decision on partitioning. The correlation between the critical percentages and the critical distances was mathematically precise in the new model, whereas this correlation is rather approximate in the Harris-Boyd model because focus on the difference between means in this model makes high precision hard to achieve. The application examples suggested that the new model is more radical than the Harris-Boyd model. CONCLUSIONS: New percentage and distance criteria, to be used for partitioning gaussian-distributed data, have been developed. The distance criteria, applied separately to both reference limit pairs of the subgroup distributions, seemed more reliable and correlated more accurately with the critical percentages than the distance criteria of the Harris-Boyd model. As opposed to the Harris-Boyd model, the new model is easily adjustable to new critical values of the percentages, should they need to be changed in the future.
Clinical Laboratory Techniques↗
Impact of subgroup prevalences on partitioning of Gaussian-distributed reference values.
BACKGROUND: The aims of this report were to examine how unequal subgroup prevalences in the source population may affect reference interval partitioning decisions and to develop generally applicable guidelines for partitioning gaussian-distributed data. METHODS: We recently proposed a new model for partitioning reference intervals when the underlying data distribution is gaussian. This model is based on controlling the proportions of the subgroup distributions that fall outside each of the common reference limits, using the distances between the reference limits of the subgroup distributions as functions to these proportions. We examine the significance of the unequal prevalence effect for the partitioning problem and quantify it for distance partitioning criteria by deriving analytical expressions to express these criteria as a function of the ratio of prevalences. An application example, illustrating various aspects of the importance of the prevalence effect, is also presented. RESULTS: Dramatic shrinkage of the critical distances between reference limits of the subgroups needed for partitioning was observed as the ratio of prevalences, the larger one divided by the smaller one, was increased from unity. Because of this shrinkage, the same critical distances are not valid for all ratios of prevalences, but specific critical distances should be used for each particular value of this ratio. Although proportion criteria used in determining the need for reference interval partitioning are not dependent on the prevalence effect, this effect should be accounted for when these criteria are being applied by adjusting the sample sizes of the subgroups to make them correspond to the ratio of prevalences. CONCLUSIONS: The prevalences of subgroups in the reference population should be known and observed in the calculations for every reference interval study, irrespective of whether distance or proportion criteria are being used to determine the need for reference interval partitioning. We present detailed methods to account for the prevalences when applying each of these types of criteria. Analytical expressions for the distance criteria, to be used when high precision is needed, and approximate distances, to be used in practical work, are derived. General guidelines for partitioning gaussian distributed data are presented. Following these guidelines and using the new model, we suggest that partitioning can be performed more reliably than with any of the earlier models because the new model not only offers an improved correspondence between the critical distances and the critical proportions, but also accounts for the prevalence effect.
Biometry↗