Efficacy of oral ganciclovir in prevention of cytomegalovirus infection in post-kidney transplant patients

We devised a diagnosis and management algorithm for acute onset of central diabetes insipidus (CDI), and conducted a retrospective evaluation of its efficacy. Fourteen patients admitted to our pediatric intensive care unit (PICU) over a three year period were diagnosed with acute CDI secondary to various brain injuries. All patients were treated as per the algorithm guidelines. The initial dose of aqueous vasopressin ranged from 0.25 to 1.0 mU/kg/h. Low sodium content solution (0-0.5 normal saline) was used to replace urine output in excess of 3 ml/kg/h and for maintenance fluid therapy. The therapeutic goals included: urine output 2-3 ml/kg/h, urine specific gravity 1.010-1.020 and serum sodium 140-145 mEq/l. The pitressin dose was adjusted as deemed necessary to achieve the aforementioned goals. Our results indicate that urine specific gravity is the most sensitive parameter to respond to treatment. It was the best determinant of the adequacy of pitressin dose as it had the best linear correlation with it (r = 0.96; p = 0.009). Urine output was second best (r = 0.93; p = 0.02), whereas no linear correlation was established between pitressin dose and serum sodium concentration, nor with serum osmolality. We conclude that the algorithm developed and used by us for the management of CDI is generally efficacious. Changes in urine specific gravity follow changes in pitressin dose very closely and thus should be used as the primary parameter for determination of intravenous pitressin dose adjustment.     

First-morning urine specific gravity and enuresis in preschool children

The object of the study was to determine whether a first-morning urine specific gravity of less than or equal to 1.015 was associated with enuresis in children 3 to 6 years old. Parents of preschool children seen at the Cleveland Clinic Foundation during a 5-month period completed a questionnaire concerning bed-wetting and voiding habits of their child and collected first-morning urine specimens for specific gravity analysis. Of 101 children, 12 had a urine specific gravity of less than or equal to 1.015 (11.9%), including seven of 73 (9.6%) nonbed-wetters, two of 19 (10.5%) bed-wetters by history (who did not wet their beds on the night of the study), and three of nine (33.3%) bed-wetters (who wet their beds on the night of the study). The 73 nonbed-wetters (72.3%) had a mean (+/- standard deviation) urine specific gravity of 1.022 (+/- 0.006); 19 bed-wetters by history (18.9%) had a mean urine specific gravity of 1.024 (+/- 0.006); and nine bed-wetters (8.9%) had a mean urine specific gravity of 1.019 (+/- 0.005). The groups' mean urine specific gravities were not significantly different (p = 0.10) and the enuretic children were not more likely to have first-morning-void urine specific gravity of less than or equal to 1.015 than nonenuretic children (p = 0.14). Enuretic children who wet their beds on the night of the study had lower mean urine specific gravity than nonbed-wetters although the difference was not significant. Therefore, we do not recommend routine use of first warning void urine specific gravity analysis for predicting presence or absence of enuresis.     

Evaluation of the CLINITEK ATLAS for routine macroscopic urinalysis

OBJECTIVES: To evaluate the performance of a new, benchtop, fully automated urine analyzer the CLINITEK ATLAS and compare it with the URICHEM 1000 CHEMSTRIP UA analyzer. Macroscopic analysis included measurement of 8 urine analyte chemistries and specific gravity by the refractive index method (SgRl). METHODS: The analytical performance studies conducted were calibration stability, precision (within-run and day-to-day), comparison of results of 437 fresh patient urine specimens, analysis of time performance, and problem logging over a 16-day evaluation period. RESULTS: Satisfactory calibration reproducibility, within-run (n = 10), and day-to-day (n = 16) precision was found because results fell within the +/- one color-block by the proposed National Committee for Clinical Laboratory Standards (NCCLS) criteria. Patient results (n = 437) from the 2 analyzers giving the same color-block agreement was found to be for pH, 52%; glucose, 92%; ketones, 86%; protein, 79%; bilirubin, 97%; leukocytes, 72%; blood, 80%; and nitrite, 98%. The concordance defined by the NCCLS criteria as the agreement of results +/- one color-block between the 2 analyzers was found to be for pH, 96%; glucose, 99%; ketones, 100%; protein, 95%; bilirubin, 100%; leukocytes, 97%; and blood 86%. The SgRl determined on ATLAS was correlated with the RD-10 Rapid Density analyzer with the following results: slope = 0.97, intercept = 0.033, r = 0.94, Syx = 0.003, for a range of values from 1.002 to 1.070. CONCLUSION: Our preliminary data indicate that the analytical performance, and automatable features for complete walk-away function of this analyzer can significantly increase the overall testing efficiency in the urinalysis laboratory.     

Hearing improvement after resection of cerebellopontine angle meningioma: case study of the preoperative role of transient evoked otoacoustic emissions

OBJECTIVE: The present study was initiated to investigate the validity of cadmium (Cd) and lead (Pb) in urine in comparison with the metals in blood as a biological marker of nonoccupational exposure of general populations to these metals as environmental pollutants. DESIGN: Peripheral blood samples, morning spot-urine samples, and 24-h total food duplicate samples were collected from 107 nonsmoking women (aged 30-59 years) in four urban and rural survey sites in Korea. METHODS: Portions of the samples were digested by heating in the presence of mineral acids, and the digests were analyzed for Cd and Pb by graphite furnace atomic absorption spectrophotometry. The metal concentrations in urine were adjusted for creatinine concentration and a specific gravity of 1.016. The analyte levels were evaluated on an individual basis (n = 107) and also on a group basis, i.e., in terms of geometric means for the survey sites (n = 4). RESULTS: Cd in urine correlated with Cd in blood on an individual as well as survey-site basis and tended to correlate with Cd in food duplicates on a group basis. The correlation of Pb in urine with Pb in blood was weaker than that of Cd in urine with Cd in blood when evaluated on an individual and survey-site basis. Pb in urine correlated with Pb in food duplicates either weakly or even negatively when examined on a survey-site basis. CONCLUSIONS: Cd in urine proved to be valid as a biological marker of environmental exposure of general populations, whereas less support was obtained for Pb in urine as an exposure marker.     

In vivo adulteration: excess fluid ingestion causes false-negative marijuana and cocaine urine test results

Drug users can be highly motivated to obtain negative results on urine drug tests and may attempt to subvert the process by in vivo adulteration. The use of herbal products for "flushing" and "detoxification" is frequently advertised as an effective means of passing drug tests. Accordingly, a study was designed to determine the effects of ingestion of two herbal products, Naturally Klean Herbal Tea and Golden Seal root, and a diuretic medication, hydrochlorothiazide. The herbal tea was prepared in 1 gal of water as specified by the manufacturer. All other products were consumed with 1 gal of water. Two control conditions in which the subject consumed only water (1 gal; 12 oz) were included. The 1-gal liquid treatments were divided into 4-qt aliquots, and 1-qt was consumed each hour for 4 h. All treatments were begun approximately 22 h after smoking of a marijuana cigarette (3.58% THC) and 22 h after intranasal administration of cocaine hydrochloride. Following all treatments with excess fluid, creatinine and specific gravity dropped in 1.5-2.0 h to levels indicative of diluted specimens (<20 mg/dL creatinine, <1.003 specific gravity). Marijuana and cocaine metabolite concentrations by immunoassay (EMIT and TDx) also dropped rapidly, and the results frequently switched from positive to negative. By the time subjects had consumed 2 qt of any fluid, they were generally producing false-negative results. For example, ingestion of excess water produced dilute specimens (<20 mg/dL creatinine; <1.003 specific gravity) in an average time plus or minus the standard error of the mean of 1.47 +/- 0.17 h (N = 5) and 1.45 +/- 0.2 h (N = 5) following smoked marijuana and intranasal cocaine, respectively. In comparison, ingestion of Klean Tea produced dilute specimens in 1.36 +/- 0.07 h (N = 4) and 1.39 +/- 0.11 h (N = 4) following marijuana and cocaine administration. Recovery of urine test measures to pre-treatment levels occurred over a period of 8-10 h. Average detection times for marijuana metabolite appeared to be slightly shorter following ingestion of 1 gal of fluids compared with ingestion of 12 oz of water as a result of the time of testing being near the end of the cannabinoid metabolite excretion phase. Consequently, negative cannabinoid results induced by fluid ingestion rarely returned to positive after excess water was eliminated. In contrast, negative cocaine results reverted to positive quickly after the dilution effects disappeared. It was concluded that excess water ingestion can produce false-negative test results, but the claims of herbal products to be an aid in passing a urine test appear to be unfounded.     

Accuracy of formulae for calculating left ventricular volumes of the equine heart

Echocardiography may be an accurate method of measuring left ventricular (LV) volumes and mass of the horse's heart. If so, studies of the heart size and hypertrophy would be possible. This study evaluated geometric models of the external and internal LV shapes, to determine which could be applied to echocardiographic measurements. We preserved 30 horses' hearts and measured their dimensions and cross sectional areas. These measurements were entered into seven formulae representing different geometric models of the ventricle and its chamber. We derived a correction factor to estimate the long axis as a fixed proportion of the external diameter, so that volumes could be determined from an M-mode or a cross sectional echocardiogram. Statistical analysis of the regressions of known volumes against calculated volumes measured by water displacement, demonstrated that the ellipsoid formula using cross sectional areas was very accurate in representing the external shape of the left ventricle (slope = 1.01 r2 = 96.3) and its chamber (slope = 0.83, r2 = 94.3). Myocardial volume, measured by subtracting internal (chamber) volume from external volume, was also calculated accurately (slope = 1.01, r2 = 96.5). The ellipsoid formula using directly measured diameter was only slightly less accurate. LV mass could be calculated by applying the specific gravity of equine myocardium, 1.05, to the myocardial volume. Formulae recommended for evaluating are, with M-mode echocardiography: [equation: see text] and with 2D echocardiography [equation: see text] where De is the external diameter, Di is the internal diameter, Ae the external area and Ai the internal area.     

Urine specific gravity and osmolarity in hypertension patients with dehydration

Results are reported from the comparative investigations of kidney concentration function by urine specific gravity and its osmolatity of 58 patients with arterial hypertension. Significant differences were found in more of the half of the patients. On the base of certain theoretical prerequisites and possibilities of technical errors was concluded that the determination of the maximal urine osmolality is a more reliable and more accurate index for the actual renal concentration ability. Urine specific gravity can be used in the everyday clinical practice due to the more convenient and easier determination. Urine osmolality must be used predominantly in scientific-clinical studies.     

Cloning of the rat brain cDNA encoding for the SLC-1 G protein-coupled receptor reveals the presence of an intron in the gene

OBJECTIVE: Glomerular filtration rate (GFR) can be estimated in patients with renal disease from plasma creatinine concentration, age, sex, and body weight according to the formula of Cockcroft and Gault. The hypothesis that this method can be improved when tubular secretion of creatinine is inhibited by cimetidine was studied in NIDDM patients. RESEARCH DESIGN AND METHODS: In 30 outpatients with NIDDM and normo- (n = 10), micro- (n = 9), or macroalbuminuria (n = 11), GFR was measured as the urinary clearance during continuous infusion of 125I-labeled iothalamate. Plasma creatinine concentration was analyzed with an enzymatic assay before and after 800 mg t.i.d. oral cimetidine was given during a 24-h period. RESULTS: Plasma creatinine rose in all patients after cimetidine administration and, as a consequence, the clearance calculated with the Cockcroft-Gault formula fell. The ratio of this formula and GFR decreased from 1.16 +/- 0.20 to 0.97 +/- 0.16 (means +/- SD). This ratio tended to be smaller in the normo- (0.93) than in the micro- (0.98) and macroalbuminuric (1.00) groups. Also, 20 patients with a BMI < 30 kg/m2 had a smaller ratio than those with a BMI > 30 kg/m2 (0.92 vs. 1.07; P < 0.05). Bland and Altman analysis showed a difference of the Cockcroft-Gault formula and GFR of 12.0 +/- 17.4 ml.min-1 (1.73 m2)-1, which decreased to -3.8 +/- 14.8 ml.min-1.(1.73 m2)-1. The same analysis of 24-h creatinine clearance with urine collection and GFR showed larger standard deviations. CONCLUSIONS: GFR can be estimated in an acceptable way from plasma creatinine concentration after cimetidine administration in outpatients with NIDDM. Despite a nonsignificant underestimation in normoalbuminuric and overestimation in overweighted patients, this method is superior to 24-h creatinine clearance with outpatient urine collection.     

Depolarization-induced tyrosine phosphorylation of p130(cas)

OBJECTIVE: To determine whether there were immediate adverse effects of an umbilical artery pH < or = 7.0 in term and near-term infants. STUDY DESIGN: All infants triaged to the newborn nursery with an umbilical artery pH < or = 7.0 from May 1993 through April 1994 (n = 37) were prospectively identified; 35 of the 37 infants were enrolled and matched with nonacidemic control infants (n = 35). Organ system dysfunction (neurologic, renal, hepatic, gastrointestinal) was evaluated either clinically or biochemically with selected blood and urine parameters. RESULTS: Acidemic and control groups were similar for pregnancy complications before labor, but acidemic infants were more often delivered by cesarean section (20/35 vs 6/35, p = 0.001). No differences existed between acidemic and control infants in gestational age, birth weight, neurologic evaluations, hearing deficits, feeding tolerance, and hepatic function. The acidemic group had a higher mean serum creatinine than control infants on day 2 of life (0.90 +/- 0.34 vs 0.71 +/- 0.12 mg/dl, p = 0.005) and a greater number of infants with a urine Chemstrip positive for heme (14/35 vs 3/35, p = 0.005). No differences existed between groups in time to first void, urine specific gravity, and number of infants with microscopic hematuria. CONCLUSION: Term and near-term infants born with an umbilical artery pH < or = 7.0 and triaged to the newborn nursery on the basis of a stable appearance in the delivery room do not have clinical manifestations of hypoxia-ischemia in the 48 hours after birth. The higher mean serum creatinine for acidemic compared with control groups is presumably prerenal in origin and results from processes responsible for profound fetal acidemia. Infants with an umbilical artery pH < or = 7.0 and assessed to be clinically well can be treated similar to nonacidemic infants.     

振动成型机力学参数对阳极炭块质量的影响

论述振动成型机激振力的计算方法,推导出详细的计算公式,并结合多台引进的振动成型机技术及国内振动成型机的设计与实践经验,给出激振力的取值范围。以此为依据计算出的激振力,经过实践检验,炭块的比重指标达到了理想数值。在生产1520 mm×790 mm×555 mm规格的阳极炭块时,当转速n=1650 r/m in、激振力F=230 kN时,生产出的阳极炭块比重值较为理想,满足工艺要求,且焙烧后的理化指标良好。     

Activated T cells and genetic restriction in celiac disease

Studies in the last decade demonstrated that in children tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) is identical to TP/GFR; TP indicating tubular phosphate reabsorption under basal conditions, without phosphate load. TP/GFR is calculated from the formula TP/GFR = SP-UP x SCr:UCr, based on simultaneous urine and blood creatinine and phosphate concentrations, and is applicable in both the fasting and non-fasting child. These studies also demonstrated that the use of Walton and Bijvoet nomogram in children may result in overestimation of TmP/GFR compared with TP/GFR calculated from the above formula. When using the formula, one should bear in mind that creatinine is used to express GFR and as a result a significant deviation from true GFR may occur in patients with renal failure. Therefore when employing TP/GFR for the investigation of the renal handling of phosphate in children, three factors should be taken into consideration: (1) the formula in reality expresses TP/CCr; (2) only data obtained by exactly the same methodology can be used as reference values; data obtained from studies in which the nomogram was utilized or in which methods other than CCr were used to measure GFR should not be used for reference; (3) in patients with renal failure, TP/CCr will significantly overestimate TP/Cinulin.     

Treatment failure and dietary habits in women with breast cancer

Although variously shaped urinary red cells have been reported in glomerulonephritic hematuria, no specific shapes with concrete definition have been proposed. This made morphological differentiation of hematuria vague and caused different results among different observers. To solve these problems and improve the diagnostic rate, we employed a uniquely shaped red cell, which only appeared in glomerulonephritic hematuria, as a probe for diagnosis. We studied 182 hematuria cases from 90 glomerulonephritic patients and 95 hematuria cases from 68 urological disease patients. Fresh urine was collected and observed by differential interference microscopy. The red cell, referred to as G1, has a distinctive doughnut-like shape with blebs and was highly specific for glomerulonephritic hematuria. Occurrence of G1 cells increased at lower pH an higher osmolality of urine. A presence of 5% or more G1 cells could be an indicator of glomerulonephritic hematuria. Specificity and sensitivity of this criterion were 100 and 73%. However, when only acidic concentrated urine (pH < or = 6.4, osmolality > or = 400 mosm/kg H2O) was used, the specificity and sensitivity increased to 100 and 99.2%, respectively. Glomerulonephritic and urological hematuria were correctly diagnosed by counting the urinary red cells with doughnut-like shape in acidic and concentrated urine. This method seems to be superior to others in diagnostic rate, simplicity and clarity.     

Hepatic steatosis during treatment with zidovudine and lamivudine in an HIV-positive patient

BACKGROUND: Polydipsia-hyponatremia is a poorly understood disorder that causes considerable mortality and morbidity. Hyponatremia in polydipsia-hyponatremia has been attributed to disturbances in antidiuretic hormone (ADH) function. Improvements in polydipsia-hyponatremia during clozapine treatment offered the chance to see if levels of ADH and other hormones associated with osmoregulation changed with improvement in biochemical and clinical measures of polydipsia-hyponatremia. METHOD: In this preliminary, longitudinal study, we studied 2 male schizophrenic patients (DSM-III-R) who had polydipsia-hyponatremia. Measures were (1) biochemical and clinical: serum sodium and osmolality, urine osmolality and specific gravity, normalized diurnal weight gain, and estimated urine volume and (2) endocrine: ADH, angiotensin II, atrial natriuretic peptide, and prolactin. Measures were collected during 2 months of baseline (typical neuroleptic) and 6 months of clozapine treatment. RESULTS: Single-case statistical procedures showed significant changes in sodium levels (a.m. and p.m.), estimated urine volume, and a.m. urine specific gravity in both patients and significantly decreased diurnal weight gain in 1 patient. Both serum and urine osmolality showed improvement, but values did not reach statistical significance. Low baseline ADH levels persisted through 6 months of clozapine treatment and showed no changes in the context of improvements in serum sodium and osmolality. No significant changes were seen in levels of angiotensin II and atrial natriuretic peptide. CONCLUSION: Given the limitations of this study, there is some evidence to suggest that the improvements in serum sodium and osmolality during clozapine treatment of polydipsia-hyponatremia may not be related to serum levels of ADH, although altered ADH receptor function cannot be ruled out. These data need to be extended in larger samples.     

Seasonal effects on concentrations of monomethylformamide in urine samples

Eleven du Pont operators participated in a special dimethylformamide metabolite (monomethylformamide, MMF) urine monitoring study to investigate a possible seasonal influence on urine metabolite concentrations. Variables considered included urine volume, MMF concentration, MMF mass, urine specific gravity, and ambient temperature. Statistical analysis revealed a 13% reduction in urine volume under hot weather conditions as a cause of increased MMF concentrations. A correction for this change in urine volume should be made subjectively.     

When the patient cannot come to the doctor: a medical housecalls program

The activation energy (Ea) of beta-N-acetylhexosaminidase (Hex, EC 3.2.1.52) was determined with 3,3'-dichlorophenylsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide as substrate, with a much higher value being found for the Hex B isoenzyme (Ea = 75.1 kJ/mol) than for the Hex A isoenzyme (Ea = 41.8 kJ/mol). This fact allowed for the development of a fast and reliable thermodynamic method to determine the isoenzyme composition of Hex in different biological specimens (serum/plasma, saliva, cerebrospinal fluid, seminal plasma, urine, and leukocyte lysates). The results in serum given by the proposed method may be superimposed upon those obtained by the heat inactivation assay of O'Brien et al. (N Engl J Med 1970;273:15-20), and the catalytic activity calculated for Hex A offers a good correlation with that obtained by using the specific substrate 4-methylumbelliferyl-N-acetyl-beta-D-glucosaminide-6 sulfate (n = 25, r = 0.953).     

Estimation of the composition of broiler carcasses from their specific gravity

An experiment was conducted to quantify the relationships between broiler carcass specific gravity and chemical composition (percentage moisture, percentage lipid, percentage protein). Carcasses of widely varying compositions were produced by feeding several dietary protein and energy combinations (52 to 64% moisture, 0.6 to 2.5% ash, 1.6 to 11.7% lipid, and 4.9 to 8.0% nitrogen). Very strong relationships were found between percentage moisture and percentage lipid (r = -0.969) and percentage moisture and percentage N (r = 0.968). Strong relationships were found between specific gravity and percentage lipid (r = -0.872) and specific gravity and percentage N (r = 0.857). Specific gravity is recommended as a means to estimate carcass fat in broiler chickens.     

Chromium-51-EDTA clearance in adults with a single-plasma sample

In 1996, a committee on renal clearance recommended a mean sojourn time-based methodology for single-sample determination of plasma clearance of 99mTc-diethylenetriamine pentaacetic acid (DTPA) to be used on adults if the patient's glomerular filtration rate (GFR) is suspected to be >30 ml/min. The main purpose of this study was to derive a mean sojourn time-based formula for calculation of 51Cr-ethylenediamine tetraacetic acid (EDTA) clearance in adults. METHODS: Two groups of patients with 51Cr-EDTA clearance (Cl) between 16 and 172 ml/min were studied. In Group I (n = 46), reference Cl was determined as a multiplasma sample, single-injection method (ClSM). Sixteen blood samples were drawn from 0 until 5 hr after a single intravenous injection of 51Cr-EDTA. In Group II (n = 1046), reference Cl was determined by the Br?chner-Mortensen four-sample clearance method (ClBM). The plasma time-activity curves of Group I were used to derive two mean sojourn time-based formulas (Formulas 1 and 2) for calculation of a single-sample clearance. Formula 1 was derived from the entire time-activity curve, whereas the derivation of Formula 2 used only the final slope of the time-activity curve. The accuracy of the two formulas and the Christensen and Groth 99mTc-DTPA formula was tested on Group II. RESULTS: Chromium-51-EDTA Cl calculated by Formula 1 was almost identical to the Cl calculated by the reference Cl method (r = 0.982; SDdiff = 5.82 ml/min). Both 51Cr-EDTA Cl calculated by Formula 2 and by the 99mTc-DTPA formula showed close correlation with the reference method (r = 0.976, r = 0.985, respectively) but systematically overestimated GFR for the whole range of clearance values by 3.5 and 3.2 ml/min (p<0.001), respectively. CONCLUSION: It is possible to get an accurate determination of 51Cr-EDTA Cl from a single-plasma sample in adults by the mean sojourn time methodology. The determination is marginally more accurate (p<0.001) if using a formula derived from the entire plasma time-activity curve than from only the final slope. The single-sample formula derived for determination of 99mTc-DTPA Cl tends slightly to overestimate GFR if used to calculate 51Cr-EDTA Cl.     

强夯法处理路基的加固效果

在强夯法处理湿陷性黄土路基施工中,为了及时掌握和了解强夯加固深度,并对加固效果进行正确评估,利用测振仪进行现场测振,通过对测得的振动波参数进行数值分析,获得强夯法有效加固深度计算公式,同时利用重力触探方法对强夯后路基承载力进行平行检验.结果表明,有效加固深度计算公式与经验公式有较好的一致性,采用测振仪测控强夯法处理湿陷性黄土路基加固效果是一种有效的新方法.     

Is urine leukocyte esterase test a useful screening method to predict Chlamydia trachomatis infection in women?

We evaluated the use of the leukocyte esterase test (LET) on first-catch urine specimens from women as a screening test to predict infection with Chlamydia trachomatis. For diagnosis, we used Abbott's ligase chain reaction (LCR) on urine specimens and isolation by tissue culture (TC) on cervical brushes. Of 4,053 women attending sexually transmitted disease and family planning clinics, 4.3% (n = 174) were positive by TC and 5.9% (n = 239) were positive by LCR. When LET was compared to TC, the sensitivity, specificity, positive predictive value, and negative predictive value were 54.0, 67.0, 6.8, and 97.0%, respectively. The corresponding performance of LET versus LCR was 53.1, 67.3, 10.1, and 95.8%. Almost half of the laboratory-confirmed chlamydial infections were negative by LET. The low specificity probably reflects multiple causes of pyuria in women and results in a low positive predictive value. LET is neither sensitive nor specific as a predictor of chlamydial infection and cannot be recommended for use as a screening test for C. trachomatis with first-catch urine samples from females from low- or moderate-prevalence populations.     

Quantification of orotic acid in dried filter-paper urine samples by stable isotope dilution

A rapid, sensitive, and specific method for quantification of orotic acid from dried filter-paper urine samples is described. The method involves stable isotope dilution with 1,3-[15N2]orotic acid analysis by gas chromatography-mass spectrometry. The assay is sufficiently sensitive to be used with solvent extraction techniques commonly used for urinary organic acid analysis. Extraction efficiencies of both native and isotopic orotic acid from dried filter paper and from water were 31% and 28%, respectively. The concentration of orotic acid in dried filter-paper urine specimens from 50 healthy controls was 1.1 +/- 0.67 (mean +/- SD) mmol/mol of urinary creatinine. The same 50 urine samples, analyzed directly from a 5-mL aliquot of liquid urine, gave values of 0.93 +/- 0.51. The correlation coefficient between the results obtained by the two different collection methods was 0.87. Age-related reference values in filter-paper samples are also reported. The concentrations, which are normalized to urinary creatinine, decrease with age. This method is applicable to rapid screening for urea cycle disorders and may also be used for carrier testing of ornithine transcarbamylase deficiency.