Barbara M. Goldsmith

Comparison of Urine Dipstick, Microscopy, and Culture for the Detection of Bacteriuria in Children

The authors compared dipstick tests for leukocyte esterase and nitrite and microscopic examination of urinary sediment with urine culture to assess whether the former tests could reliably rule out bacteriuria in specimens from children. The authors studied urine specimens from 1010 infants and children younger than age 18. Compared with culture at ≥105 colony forming units (cfu)/ml, the sensitivities of leukocyte esterase, nitrite, and microscopic examination of white blood cells (≥5 wbc/hpf) or bacteria (in at least moderate numbers) were 76 percent, 29 percent, 82 percent, and 80 percent, respectively. The specificities of the same tests were 81 percent, 99 percent, 81 percent, and 83 percent, respectively. Compared with culture at ≥104 cfu/ml, the sensitivities of the tests were 64 percent, 21 percent, 64 percent, and 59 percent; the specificities were 82 percent, 99 percent, 81 percent, and 83 percent, respectively. The negative predictive values of leukocyte esterase and microscopic examinations of urinary sediment for white blood cells and bacteria were all 95 percent (≥104 cfu/ml) or 98 percent (≥105 cfu/ml). The authors conclude that the leukocyte esterase test is as accurate as sediment microscopy in identifying urine specimens from infants and children harboring <10 4 or <105 cfu/ml.

Pharmacokinetics of cyclosporine after renal transplant in children.

The pharmacokinetics of cyclosporine and the relationship between blood levels and average drug concentration were prospectively evaluated in 18 children 1 month after renal transplantation. All children had normal renal function and no hepatic or gastrointestinal dysfunction. Cyclosporine was administered after an overnight fast, and serial blood samples were drawn over a 24‐hour period. Analysis of cyclosporine levels was performed by means of monoclonal radio immunoassay on whole blood. Children were divided into three age groups for comparison: 2–5 years, 5–10 years, and >10 years. There were no differences between age groups in serum protein, serum lipids, or hemoglobin levels, or in the pharmacokinetic parameters of cyclosporine except as follows: significant differences were noted in cyclosporine dose based on body weight, apparent steady‐state volume of distribution, and apparent blood clearance, with the youngest children (2–5) requiring higher doses, a relative greater distribution, and exhibiting more rapid drug clearance than those > 10 years of age. In addition, we observed diurnal variation in trough levels, with morning levels (0 hr) significantly higher than those obtained in the evening (12 hours after administration of cyclosporine). Trough levels demonstrated a fair correlation with area under the concentration‐time curve (AUC) and average concentration (Cav), but an abbreviated kinetic profile using cyclosporine levels 1 and 3.5 hours after administration accurately predicted AUC.

Effects of Carbamazepine on Cyclosporine Metabolism in Pediatric Renal Transplant Recipients

This study documents a pharmacokinetic interaction between carbamazepine and cyclosporine (CsA) in pediatric renal transplant recipients. Noncompartmental steady‐state CsA pharmacokinetics were determined in three pediatric renal transplant recipients who were receiving both CsA and carbamazepine as long‐term therapy (carbamazepine group) and in three matched renal transplant subjects who were not receiving carbamazepine (control group). Even though the mean daily dosage of CsA was consistently higher in the carbamazepine group than in the control group (16.2 mg/kg/24 hrs vs 10.8 mg/kg/24 hrs, respectively), the predose trough CsA blood concentrations were significantly lower in the carbamazepine group (57 ng/ml vs 162 ng/ml, respectively; p=0.0023). Mean average steady‐state blood concentrations of CsA (Cav) per mg of CsA administered were less than 50% in the carbamazepine group compared with the control group. This reflects either an induction of CsA hepatic metabolism or a reduced systemic bioavailability (possible induction of pre‐hepatic metabolism) by concurrent use of carbamazepine.

Glucose meters – fit for clinical purpose

Abstract Glucose meters have improved considerably since they were first introduced in 1960, but many questions are being asked about their accuracy and reliability in certain clinical situations. These questions have arisen because of the widespread use of these meters into clinical areas they have not been designed for such as critical care. The lack of understanding by some health professionals on factors that affect glucose results, such as sample type, glucose test strip methodologic limitations, calibration to recognized reference methods, and interferences, leads to misleading results that may affect patient care. Much debate continues on the quality specifications for glucose meters. Because there is an extensive use of these meters in different clinical scenarios, the setting of quality specifications will remain a challenge for regulatory and professional organizations. In this article, we have attempted to collect and provide relevant information addressing the limitations above. Pivotal to obtaining the best quality of results is education, particularly for diabetic patients monitoring their glucose. The International Federation of Clinical Chemistry and Laboratory Medicine through its Point-of-Care Testing Task Force and its Working Group on Glucose Point-of-Care Testing is actively working toward improving the quality of glucose results by improving education and working with the industry to improve strip performance and work toward the better standardization of strips.

Teaching pediatric laboratory medicine to pathology residents

CONTEXT Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine. OBJECTIVE Childrens Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs. DATA SOURCES Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine. CONCLUSIONS Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

Effects of fenfluramine on social behavior in autistic children

Deficit in social interaction is a primary component of infantile autism. However, in the majority of drug studies, social interaction has not been measured consistently over time. Therefore, we examined, in a crossover design, the effect of fenfluramine on the social interactions of seven autistic children. Social interaction was measured one to three times per week, while the children were in open placebo, placebo, or drug phases of the study. The results demonstrated that the effect of fenfluramine on social interaction was inconsistent across children, with two children possibly demonstrating a tolerance to the behavioral effects of the drug. The results are discussed with respect to genetic and pharmacologic factors.

Systemic membrane defect and the inhibition of lymphocyte capping in Duchenne Muscular Dystrophy

Eight reversible inhibitors were used to study decreases in lymphocyte capping in patients with Duchenne Muscular Dystrophy (DMD) when compared to controls. The inhibitors included hydrocortisone, chlorpromazine, calcium ionophore, Cytochalasin D, propranolol, dibucaine, fluoride and azide. All of these inhibitors disrupt cap formation. Mononuclear leukocytes from DMD patients and controls were isolated from whole blood, incubated with fluorescein-conjugated polyvalent antisera and inhibitor, induced to form caps, and the caps counted using a fluorescent microscope. Cell viabilities and morphology were assessed. After removal of inhibitor, the cells were recounted. All of the inhibitors significantly lowered capping in controls (p less than 0.001), but this effect was seen with only four out of the eight inhibitors in DMD patients. Dibucaine and azide were less inhibitory in patients (p less than 0.005, p greater than 0.05, and p greater than 0.05 respectively) while capping in patients was not inhibited by fluoride and hydrocortisone (p greater than 0.5). The lack of hydrocortisone inhibition suggests that the differences in capping between DMD patients and controls may lie within the membrane itself, rather than its associated components (i.e. cytoskeletal network), and that the defect occurs toward the beginning of the capping sequence.

Determination of a reference range for whole blood serotonin in a pediatric population using high pressure liquid chromatography with electrochemical detection.

Whole blood serotonin (5HT) concentrations were measured in a group of children and adolescents to determine a reference range for this population. Blood was collected after at least a 6-hour fast, mixed with ascorbic acid and EDTA, and frozen at -70 degrees C until analysis. 5HT was determined by HPLC with electrochemical detection. Matrix-matched whole blood standards and controls were used to determine 5HT concentrations, and monitor performance of the assay. 5HT concentrations in boys ranged from 0.53 to 3.13 mumol/L (mean = 1.27, SD = 0.47) while the range for girls was 0.63 to 2.46 mumol/L (mean = 1.21, SD = 0.47). There was no significant difference in 5HT concentrations between boys and girls, nor was there any significant change in 5HT concentration with age. The nonparametric central 95 percent reference range for boys and girls was determined to be 0.64-2.45 mumol/L.

Multiple Myeloma: The Case of the Disappearing Band

This case study presents a patient with multiple myeloma whose serum specimen exhibits 2 distinct bands in serum protein electrophoresis but only one band in immunofixation electrophoresis. This latter, single band corresponds to the M-spike. An investigation is presented to determine the identity of this disappearing or phantom band. Furthermore, this case is used as a teaching point to explain the criteria used for staging multiple myeloma, how a cell can become a myeloma propagating cell, methods that can be used to identify unexpected bands in serum protein electrophoresis, possible explanations for bands in the beta region, the usual treatment regimens in multiple myeloma and finally specimen collecting and handling procedures for serum protein electrophoresis.

Non-linearity within the primary measurement range of a lipase assay as the cause of a gap in the interpatient lipase results distribution

OBJECTIVES Interpatient distribution data for lipase (Roche Cobas® assay) showed an unexpected data gap, where no results were reported. This gap occurred beginning at a point just above the assays primary measurement range (i.e., above the cutoff (300U/L) for automated repeat-on-dilution). Calculation or other errors within the automated dilution process were ruled out. Linearity of assay results was investigated. DESIGN AND METHODS Linearity of experimental sample dilution series data was assessed by correlation coefficient, intercept, and constancy of slope. RESULTS Dilution experiment data demonstrated a discontinuity of results between 300 and 400U/L consistent with the observed gap in patient data. Although data within the presumed linear range of the assay had a high linear correlation coefficient (r2>0.99), a non-zero intercept and progressively variable slope were inconsistent with linearity. Although the assay was assessed as linear by the College of American Pathology linearity survey, survey data also demonstrated non-linearity for this assay when analyzed for slopes and intercept. CONCLUSIONS Non-linearity in the presumed linear range of an assay can produce gaps in patient data above a repeat-on-dilution cutoff. As in this instance, CAP linearity surveys may not identify certain forms of non-linearity.