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.     

Value of nucleic acid amplification methods Amplicor (Roche) and Amplified MTD (Gen-Probe) for the rapid diagnosis of tuberculosis

The nucleic acid amplification methods: Amplicor (Roche diagnostic) and AMTD Amplified Mycobacterium tuberculosis Test Direct-(Gen-Probe) were tested in 278 specimens from 231 patients suspect to be affected by mycobacterial infection. When results of both methods: Amplicor and AMTD were compared with culture results (specimens grow M tuberculosis) and clinical characteristics, the sensitivity and specificity were 91.4% and 97.9% respectively for pulmonary specimens and 61.1% and 98.6% respectively for extrapulmonary specimens. Detection of amplification inhibitors reduce false-negative reactions and control of specimen with microscopic negative and amplification positive, reduce the false-positive reactions. Amplicor and AMTD kits can be used in clinical laboratories. Both assays have the potential to reduce the time of tuberculosis diagnosis to one day.     

Prevalence of illicit drugs detected in the urine of women of childbearing age in Alabama public health clinics

Each year, it is estimated that from 350,000 to 739,000 U.S. infants are exposed in utero to one or more illicit drugs. To estimate the prevalence of and risk factors for illicit drug use by women of childbearing age in Alabama, during 2 months in 1991 the authors collected patient-reported histories, clinical histories, and urine specimens from 6,195 women statewide attending public health maternity clinics, family planning clinics, and a high-risk referral obstetrical clinic. Blind drug screening of urine specimens for marijuana, cocaine, opiates, barbiturates, and amphetamines was performed with the use of a fluorescent polarization immunoassay. The overall prevalence of positive results for drugs tested was 10.1 percent, including 8.4 percent of the 3,554 pregnant and 12.3 percent of the 2,571 nonpregnant women screened. The drugs most frequently detected were marijuana and cocaine. Characteristics of the subjects associated with a higher prevalence of positive results for any drug tested or for marijuana included white race, older age, being divorced, non student occupation, having 12 or less years of education, attending a clinic located in a suburban county, self-reported substance use, increased risk for human immunodeficiency virus infection, and reproductive history. Characteristics of women with positive screening for cocaine results were similar to those who tested positive for any drug, except that the prevalence of cocaine was higher among black women and those attending urban county clinics and did not vary by years of education. Patient-reported histories of drug use were insensitive in identifying women who had positive drug screening results (sensitivity, 6.3 percent; specificity, 98.2 percent). Thus, in this study,the use of illicit drugs among women of childbearing age attending public clinics in Alabama was common and emphasizes the need for targeted drug education and interventions to reduce the impact of drug use on this high-risk population.     

Urinary excretion half-life of 11-nor-9-carboxy-delta9-tetrahydrocannabinol in humans

The excretion of marijuana metabolites occurs over an extended period of time, yet few studies have been designed for accurate estimation of excretion half-lives. The authors monitored excretion of the primary urinary metabolite of marijuana, 11-nor-9-carboxy-delta9-tetrahydrocannabinol (THCCOOH), by gas chromatography-mass spectrometry in a controlled clinical study of marijuana smoking that included measurement of the drug in each urine void collected during the 3-week study. Terminal excretion half-lives of THCCOOH were determined in six healthy male subjects with histories of marijuana smoking; the study was conducted on the clinical research unit of a major medical institution. Subjects smoked a single marijuana cigarette (placebo, 1.75% or 3.55% THC) each week. Urine specimens (N=953) were analyzed under blind conditions for THCCOOH by gas chromatography-mass spectrometry. Mean+/-SEM half-lives calculated by the amount remaining to be excreted method after the low and high doses were 31.5+/-1.0 hours (range, 28.4 to 35.3 hours) and 28.6+/-1.5 hours (range, 24.9 to 34.5 hours), respectively, when a 7-day monitoring period was used. The amounts of THCCOOH excreted over a 7-day period were 93.9 +/-24.5 microg (range, 34.6 to 171.6 microg) and 197.4+/-33.6 microg after the low- and high-dose sessions. Longer half-lives, 44.3 to 59.9 hours, were obtained with a 14-day sample collection. This study documents the prolonged excretion of THCCOOH in urine and emphasizes the importance of study design in the precise estimation of terminal excretion half-lives. A sensitive analytical method and a prolonged specimen collection period are important study considerations in the monitoring of marijuana excretion.     

Magnetic resonance coronary angiography in heart transplant recipients

BACKGROUND: Magnetic resonance angiography (MRA) using segmented k-space fast low-angle shot imaging has recently been used to demonstrate the proximal coronary arteries in healthy subjects and in patients with coronary artery disease. We assessed the sensitivity and specificity of coronary MRA in heart transplant recipients and investigated the feasibility of coronary MRA in patients with metallic sutures and clips in the chest. MATERIALS AND METHODS: Sixteen cardiac transplant patients aged 57.2 +/- 7.9 years (mean +/- SD) were recruited. Forty-eight arterial segments were evaluated, including the left main artery (LMA), left anterior descending artery (LADA) and right coronary artery (RCA). We excluded the left circumflex artery which could not be imaged accurately. The average time between heart transplant operation and MRA was 6 years, whereas that between MRA and X-ray angiography was 4 months. The coronary MRA was interpreted by two experienced investigators who were blinded to the coronary X-ray angiography results. Similarly, the coronary X-ray angiography results were interpreted by two experienced investigators blinded to the MRA results. The coronary arterial segments were classified by MRA as being normal or as having an amount of disease that was significant (> 50% lesion) or insignificant (< 50% lesion). RESULTS: There were 28 true-negative, five true-positive, four false-negative and six false-positive results. Of the 28 true-negative cases, 13 were in the LMA, six in the LADA and nine in the RCA. There was one false-positive LMA, two false-positive LADA and three false-positive RCA stenoses. There were four false-negative results in the LADA and one in the RCA. Clips precluded evaluation in one LMA, one LADA and one RCA. One LMA and one LADA were not evaluated as a result of poor images. One false-positive RCA stenosis was caused by a metallic clip. Three of the false-negative LADA stenoses had lesions in the distal third of the artery. The sensitivity, specificity, negative and positive predictive values were generally poor for the left coronary artery. The best results were for the RCA (sensitivity 100%, specificity 75%, positive predictive value 50% and negative predictive value 100%). The specificity in the left coronary arteries (LMA and LADA) was 86%, but the other indicators were all poorer. For the RCA, LMA and LADA combined, the overall sensitivity was 56%, specificity 82%, predictive accuracy 45% and negative predictive value 88%. In three patients, < 50% RCA lesions were seen in the MRA data, which were all confirmed by angiography. No < 50% lesions were seen in the LMA or in the LADA by MRA or by X-ray angiography. CONCLUSION: Coronary MRA using the segmented fast low-angle shot technique is feasible in heart transplant recipients but the sensitivity and specificity of this method are limited. Further developments in coil design, rapid imaging techniques and respiratory monitoring methods are necessary to improve the accuracy of coronary MRA.     

A new screening protocol combining urine beta-core fragment and ultrasonography for Down syndrome detection

OBJECTIVE: Our purpose was to ascertain the screening efficiency of a new midtrimester Down syndrome detection protocol that combines maternal urine testing and ultrasonographic examination. STUDY DESIGN: In a prospective study, beta-core fragment, the stable end product of human chorionic gonadotropin metabolism, was measured in maternal urine. The results were standardized for urine creatinine levels. The study was performed in women undergoing midtrimester genetic amniocentesis (15 to 24 weeks' gestation). Urine beta-core fragment values were expressed as multiples of the normal median for gestational age. The screening performance of a combination of ultrasonographic parameters and urine beta-core values for Down syndrome detection was determined. RESULTS: A total of 511 singleton pregnancies in women undergoing amniocentesis were studied, 18 of the women (3.5%) had a Down syndrome fetus. A urine beta-core fragment level > or = 97th percentile had a sensitivity of 61.1% and a false-positive rate of 3.2%. An abnormal prenatal screen was defined as a urine beta-core level > or = 97th percentile, increased nuchal thickness (> or = 5 mm), or the presence of gross structural defects. Corresponding values for the screening efficiency of an abnormal prenatal screen were sensitivity of 77.8% and a false-positive rate of 4.1%. With an abnormal prenatal screen the odds ratio is 82.8 (95% confidence interval 22.6 to 364.9) for having a Down syndrome fetus. CONCLUSION: The presence of an abnormal maternal urine beta-core level, a gross ultrasonographic anomaly, or increased nuchal thickness had a high detection rate and a low false-positive rate for Down syndrome. This novel screening algorithm is useful for further delineating the risk status in patients at high risk who are reluctant to undergo or decline genetic amniocentesis.     

Combining beta-core fragment and total oestriol measurements to test for Down syndrome pregnancies

Recent articles by Cuckle et al., Canick et al., and Isozaki et al. have evaluated urine beta-core fragment as a screening test for Down syndrome in second-trimester pregnancies. They found over four-fold elevation of beta-core fragment levels in Down syndrome pregnancies, and between 62 and 88 per cent detection of this trisomy at a 5 per cent false-positive rate. Urine beta-core fragment may be a superior screening test for Down syndrome pregnancies. In the present study, urinary total oestriol has been evaluated as a marker to use in combination with beta-core fragment in screening for Down syndrome pregnancies. The two markers were evaluated separately in relation to the urine creatinine concentration. To amplify screening performance, we evaluated the ratio of beta-core fragment to total oestriol levels (creatinine-independent). beta-core fragment and total oestriol levels were determined (normalized to creatinine, ng/mg creatinine) in urine samples from 480 unaffected and 12 Down syndrome pregnancies, collected consecutively at a single prenatal diagnosis centre. The median beta-core fragment level in Down syndrome cases was 4.5 MOM. Fifty-eight per cent of Down syndrome cases had beta-core fragment levels exceeding the 95th centile of unaffected pregnancies. The median total oestriol level in Down syndrome cases was 0.33 MOM. Forty-two per cent of Down syndrome cases had total oestriol levels exceeding the 95th centile of unaffected pregnancies. We investigated the ratio of the two determinants (beta-core fragment, ng/ml divided by total oestriol, ng/ml) in our sample set. The median beta-core fragment:total oestriol ratio in Down syndrome cases was 13 MOM. Seventy-five per cent of Down syndrome cases had a ratio exceeding the 95th and the 99.5th centile of unaffected pregnancies. Total oestriol complements beta-core fragment in urine screening for Down syndrome pregnancies. A test measuring the ratio of the two urine determinants may be a significant improvement over current serum methods for detecting Down syndrome.     

Apolipoprotein A-I mutations and low high density lipoproteinemia

Urinary catecholamines (CAs) and their metabolites are usually measured during the process of diagnosing pheochromocytoma (pheo), but a 24-hour urine collection is not convenient for outpatients. Since 1987 we have utilized "spot" urine metanephrine (MN) and normetanephrine (NMN) assays for management of patients with pheo or adrenal incidentaloma. MN and NMN were measured by radioimmunoassay in 82 patients with surgically proved pheo and 15 patients with incidentaloma. In 10 patients with pheo, MN and NMN were measured with fractional every-3-hour urine samples, which were accumulated and then measured as a 24-hour urinary specimen. Fractions of 3-hour MN and NMN excretion were constant (MN 98.5 +/- 9.6%, NMN 97.6 +/- 10.8%; 24-hour MN and NMN 100%). The average levels of MN and NMN in patients with pheo were 6801 ng/mg creatinine (Cr) (range 93-88,248, median 1426) and 5627 ng/mg Cr (range 219-31,528, mean 3190), whereas the MN and NMN levels in patients with incidentaloma were 123 ng/mg Cr (range 36-246, mean 133) and 251 ng/mg Cr (range 84-472, mean 220), respectively. When we selected a cutoff value for MN + NMN of 1000 ng/mg Cr, the sensitivity was 97.6% and the specificity 100% for diagnosing pheo. When the standard was set as > 500 ng/mg Cr for either MN or NMN, both the sensitivity and specificity were 100%. The assay for MN and NMN is simple and effective, not only for screening but for diagnosing pheo and managing incidentaloma.     

Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) enhance lipopolysaccharide binding to neutrophils via CD14

BACKGROUND: Microalbuminuria is an early marker of prognostic significance in diabetic renal disease. However, testing for microalbuminuria in a timed sample of urine using the double antibody radioimmunoassay (RIA) method is cumbersome and requires special laboratory facilities. Recently, a test strip for microalbuminuria, the Micral Test was available and we evaluated the performance of this test strip as a screening method for detection of microalbuminuria. METHODS: One hundred consecutive diabetic patients who were tested to be dipstick-negative (Albustix) for proteinuria were enrolled for the study. Micral Tests were performed on a paired first morning and random urine specimen from the same patient and the results compared with a timed 24-hour urine measurement of urine albumin excretion using the RIA method. RESULTS: Eighteen specimens were tested positive by the RIA method with a urinary albumin range of 32-177 mg/24 hours. With the Micral Test, the following sensitivity, specificity, positive and negative predictive values were obtained: 66.7%. 97.6%, 85.7% and 93.0% for the first morning urine specimens, and 77.8%, 91.5%, 66.7% and 94.9% for the random urine specimens. CONCLUSIONS: These results suggest that Micral Test with either the first morning or random urine specimen offers a simple, reliable, rapid and convenient method for screening of microalbuminuria in the diabetic patient.     

Clinical evaluation of the Serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides

The Serum CrossLaps One Step ELISA is a sandwich assay using two monoclonal antibodies specific for a beta-aspartate form of the epitope EKAHDGGR derived from the carboxy-terminal telopeptide region of type I collagen alpha1-chain. Our objective was to assess the clinical value of the Serum CrossLaps assay for monitoring antiresorptive therapy in osteoporosis treatment. Samples obtained from postmenopausal women treated with different doses of cyclic or continuous hormone replacement therapy (HRT) with an estrogen analog (tibolone) or with a bisphosphonate (ibandronate) were measured in the Serum CrossLaps One Step ELISA at baseline and at various time points during therapy. The corresponding urine samples were measured in the urine CrossLaps ELISA and corrected for creatinine excretion. The serum CrossLaps measurements and corresponding urinary CrossLaps measurements were highly correlated (r >0.8 for all studies). The serum and urine CrossLaps measurements showed a significant decrease among the women treated with clinically relevant doses of either of the antiresorptive agents. Furthermore, the annual percentage change in bone mineral density (BMD) correlated with the measured changes in CrossLaps concentration. The serum CrossLaps assay showed a specificity of 83-100% and a sensitivity of 59-83% for assessing BMD changes. The corresponding values for the creatinine-corrected urinary measurements were 83-92% specificity and 68-79% sensitivity. We conclude that performance of the convenient Serum CrossLaps One Step ELISA is at least equivalent to that of the urine text for follow up of antiresorptive treatment in osteoporosis. Further studies are needed to optimize its use in this and other clinical applications.     

Primary cryptococcal infection of the larynx in a patient with AIDS: a case report

From January of 1990 to December of 1992, 6,954 consecutive cytologic breast fine-needle aspiration biopsies (FNAB) were performed at the Laboratory of Pathology of Sant'Anna Hospital in Turin. Of these cases 62% were solid nodes, 35% were cystic nodes, and 2.7% were nonpalpable breast lesions (stereotaxic or ultrasound guided FNAB). We verified 4,110 cases: 913 cases underwent surgery and 3,197 were evaluated clinically, and/or cytologically, and/or with mammography at least 1 yr after the first diagnosis, or checked with the database of the Tumor Registry of Turin. In our series the FNAB sensitivity was 94.6%, specificity was 99.9%, accuracy was 98.8%, inadequate samples were 6.4%, false-negative rate was 1.4%, and false-positive rate was 0.3%. Our results indicate that the use of cell block improves sensitivity (from 85.2 to 94.6%) and strongly reduces false-negative results (from 3.9 to 1.4%). We conclude that FNAB is a discriminant procedure to the surgical biopsy in cases with clinical, ultrasound, or mammographic low or intermediate suspect, contributing to allow a high malignant/benign surgical biopsy rate and to reduce the need for frozen section diagnosis and medical costs.     

Urinary protein excretion of semidomesticated mink in a chronic methylmercury study

A model using semidomesticated mink was set up to study the effects of chronic oral methylmercury exposure in piscivorous mammals. Three groups of mink were fed daily with diets containing approximately 0.1, 0.5, and 0.9 micrograms/g of total mercury. Piscivorous and non-piscivorous fish, naturally contaminated with methylmercury, were used to prepare diets. Renal injury was evaluated using total urine protein/creatinine ratio and differentiation of urinary low-molecular-weight and high-molecular-weight proteins on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The significance of the total urine protein/creatinine ratio data was assessed by comparing the results to a 95% group-based reference interval. The values for total urine protein/creatinine ratio did not reveal any significant increased excretion, and no dose-related trends were observed within the reference interval. Overall the total urine protein data did not suggest renal damage. Analysis of the SDS-PAGE electrophoretograms did not suggest the presence of any persistent glomerular damage in any group. High-molecular-weight proteins were not detected more frequently for any of the dose groups. During the adaptation phase, the B2M-like protein band was not remarked during the visual analysis of the gels. The B2M-like protein band was remarked during the gel analysis only several weeks into the exposure phase. This B2M-like protein band was more prevalent in urine samples taken from minks in the 0.5 and 0.9 micrograms/g groups than in the 0.1 microgram/group. These latter data, however, did not allow an evaluation of a quantitative dose-response excretion with time. The B2M-like data are suggestive of very minor renal injury.     

Stimulation of the collagen alpha 1 (I) endogenous gene and transgene in carbon tetrachloride-induced hepatic fibrosis

1. The diurnal pattern of urinary estradiol and creatinine excretion was investigated in order to evaluate the relationship between total estradiol excretion per day and the estradiol concentration or the estradiol-to-creatinine ratio from single urine samples in female common marmosets (Callithrix j. jacchus). 2. During a 36-day period, urine was collected from five adult female marmosets in 3-hr intervals during the light time of an LD 12:12 (400:0.1 lx) which corresponded to the animals' activity time. 3. Estradiol concentration was determined by radioimmunoassay after glucuronidase treatment and creatinine concentration was measured photometrically. 4. Concentration and amount of excreted estradiol, and the creatinine concentration showed a distinct diurnal pattern with significantly higher levels at the beginning of the activity time compared to later sampling times. 5. No diurnal pattern was present in the estradiol-to-creatinine ratio, but the difference between lower follicular and higher luteal phase levels of estradiol excretion remained significant in the 36-day period. 6. Correlation analyses revealed significantly positive correlations between the total estrogen mass excreted per day and the estradiol-to-creatinine ratio in "morning urine" samples. 7. Thus the estradiol-to-creatinine ratio of single urine samples collected at the beginning of the activity time provides a reliable estimate of total estrogenic output in this species. 8. Studies of the circadian pattern of urinary hormone excretion, however, require total urine sampling.     

Effects of cicletanine on the urinary excretion of prostanoids and kallikrein, and on renal function in man

The effects of cicletanine, a new antihypertensive agent, on the prostaglandin-kallikrein system and the renin-angiotensin system were studied. A single oral dose of 200 mg cicletanine or placebo was administered to 9 healthy male volunteers, with samples of blood and urine obtained before and 2 hours after drug administration. Cicletanine increased the urine flow, urinary excretion of sodium, and fractional excretion of sodium by 47%, 115%, and 104%, respectively. While the excretion of 6-keto-prostaglandin-F1 alpha was enhanced significantly, urinary excretion of thromboxane-B2, prostaglandin-E2, and kallikrein were unchanged. Cicletanine also did not alter plasma renin activity, plasma aldosterone concentration, or creatinine clearance. These observations suggest that cicletanine may suppress sodium reabsorption at the nephron, and it may stimulate prostacyclin generation with no effect on that of thromboxane-A2. Thus cicletanine may be beneficial in the management of cardiovascular disorders in which the equilibrium between prostacyclin and thromboxane is disturbed.     

Somatosensory- and motor-evoked potential monitoring without a wake-up test during idiopathic scoliosis surgery. An accepted standard of care

STUDY DESIGN: This was a retrospective study of 500 patients undergoing corrective surgery between 1987 and 1997 for spinal deformity caused by idiopathic scoliosis. OBJECTIVES: To report the sensitivity and specificity of somatosensory-evoked and neurogenic motor-evoked potentials monitoring and the requirements for an intraoperative wake-up test for all idiopathic scoliosis surgeries at a single institution. SUMMARY OF BACKGROUND DATA: Intraoperative monitoring is recommended for use during corrective spinal surgery. Accepted monitoring standards and requirements for an intraoperative wake-up test are still debated. METHODS: The study group consisted of 500 patients undergoing corrective surgery for idiopathic scoliosis between 1987 and 1997. All patients were monitored using somatosensory-evoked and neurogenic motor-evoked potential techniques, using a standard protocol developed at this institution. RESULTS: The false-positive rate (significant data change without postoperative neurologic deficit) was 0.014% (n = 7). The true-positive rate (degradation of data that met warning criteria, with a corresponding postoperative neurologic deficit) was 0.004% (n = 2). No false-negative results (normal data during with a postoperative neurologic deficit) were seen. The sensitivity of combined somatosensory-evoked and neurogenic motor-evoked potential data in predicting neurologic status was 98.6%, and the specificity of normal data predicting normal findings in a neurologic examination was 100%. CONCLUSION: Combined somatosensory-evoked and neurogenic motor-evoked potentials monitoring during idiopathic scoliosis surgery represents a standard of care that obviates the need for an intraoperative wake-up test when reliable data are obtained and maintained.     

Proteinuria is still useful for the screening and diagnosis of overt diabetic nephropathy

OBJECTIVE: To assess the performance of urinary total protein measurements in timed 24-h urine collection (24-h UP) and in a diurnal random urine specimen (RUS) for the screening and diagnosis of overt diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 167 diabetic patients (20 type 1 and 147 type 2 diabetic patients; 78 women and 89 men), aged 20-84 years, collected 217 timed 24-h urine specimens. Albumin was measured by immunoturbidimetry, total protein by sulfosalicylic acid technique, and creatinine by Jaffe's method. According to the timed 24-h urinary albumin excretion rate (UAER), samples were divided into three groups: normoalbuminuric (NORMO) (UAER < 20 micrograms/min; n = 84), microalbuminuric (MICRO) (UAER 20-200 micrograms/min; n = 78), and macroalbuminuric (MACRO) (UAER > or = 200 micrograms/min; n = 55). Eighty-six patients also collected 105 RUSs (NORMO, n = 47; MICRO, n = 37; MACRO, n = 21), and urinary protein concentration (UPC) and urinary protein-to-creatinine ratio (UPCR) were measured. The receiver operating characteristics (ROC) curve approach was used to analyze the performance of the diagnostic tests. RESULTS: Spearman's coefficient of correlation of 24-h UAER versus 24-h UP was 0.95 (P < 0.001), and of 24-h UAER versus UPC and UPCR were 0.77 and 0.72, respectively (P < 0.001). The calculated areas (+/- SEM) under the ROC curve for the diagnosis of over diabetic nephropathy were 0.9987 +/- 0.001 for 24-h UP, 0.9926 +/- 0.006 for UPC, and 0.9751 +/- 0.014 for UPCR. In the ROC curves, the first points with 100% sensitivity were 541 mg (95.7% specificity) for 24-h UP, 431 mg/l (92.9% specificity) for UPC, and 0.2 (76.2% specificity) for UPCR. CONCLUSIONS: Measurements of proteinuria presented almost perfect accuracy for the screening and diagnosis of overt diabetic nephropathy. Protein measurement in spot urine is a reliable and simple method for the screening and diagnosis of overt diabetic nephropathy.     

Pitfalls in HIV testing. Application and limitations of current tests

Enzyme-linked immunosorbent assay (ELISA) and Western blot assay are the most commonly used laboratory tests for HIV infection. Both detect antibodies to HIV. ELISA results are based on detection of antigen-antibody complexes by using antibodies labeled with an enzyme that produces a color change in the presence of a specific substrate. Currently licensed ELISA tests have greater than 98% sensitivity and specificity for HIV. Western blot analysis detects antibodies to specific HIV antigens and is best used as a confirmatory test. In spite of the high sensitivity and specificity of both tests, false-positive and false-negative results do occur. Physicians should be aware of specific causes of inaccurate results. In individual cases, knowledge of the patient's history and the criteria used by the laboratory performing the test is important.     

Functional parameters and 99mtechnetium-dimercaptosuccinic acid scan in acute pyelonephritis

The diagnostic value of 99mtechnetium-dimercaptosuccinic acid (DMSA) scintigraphy, ultrasonography and renal functional parameters [urine N-acetyl-beta-D-glucosaminidase (NAG)/creatinine and urine albumin/creatinine quotients] in acute pyelonephritis (APN) were studied in 39 children (28 girls, 11 boys, median age 9 months, range 2 weeks to 9.4 years, 28 patients < 1 year, 11 patients > 1 year) with first-time urinary tract infection. Ultrasonography of the urinary tract was performed on admission and together with DMSA scintigraphy (< 10 days from admission). Urine NAG/creatinine and urine albumin/creatinine quotients were measured daily and after 6-8 weeks. Ultrasonography revealed abnormalities in 12 of 39 (31%) patients [11/32 patients (34%) with positive DMSA scintigraphy], while DMSA uptake defects were present in 32 of 39 (82%) patients [21/28 < 1 year (75%), 11/11 > 1 year (100%), P = 0.08]. Urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in children < 1 year with APN, as well as in non-renal fever controls, than in older children. However, in both age groups the urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in APN than in non-renal fever. The urine NAG and albumin excretion decreased rapidly after the initiation of antimicrobial therapy and had normalized at 6-8 weeks. The size and grade of the DMSA uptake defect (DMSA score) did not correlate with duration of disease at admission, maximum C-reactive protein or maximum fever. The urine NAG/creatinine quotient in the children < 1 year showed, however, a significant correlation with the DMSA score (r = 0.58, P < 0.05), while no correlation was found in the older children. We conclude that DMSA scintigraphy is a sensitive method to confirm the clinical diagnosis of APN, although a substantial number of infants appear to have normal scans. Early determination of the urine NAG/creatinine and albumin/ creatinine quotients may further improve the diagnostics in the infant.     

Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions

The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers.     

Diagnosis of infection in ununited fractures. Combined imaging with indium-111-labeled leukocytes and technetium-99m methylene diphosphonate

The results of combined scintigraphy in which indium-111-labeled leukocytes and technetium-99m methylene diphosphonate were used were compared with the results of cultures of open bone at 102 sites of delayed union or non-union, to determine the effectiveness of this combination as a preoperative indicator of osteomyelitis. There were twenty-five true-positive, fifty-nine true-negative, eleven false-positive, four false-negative, and three indeterminate interpretations, yielding, for the diagnosis of osteomyelitis, a sensitivity of 86 per cent, a specificity of 84 per cent, an accuracy of 82 per cent, a positive predictive value of 69 per cent, and a negative predictive value of 94 per cent. There were few false-negative scans; false-positive results were most likely at a metaphyseal site adjacent to a joint in which there was post-traumatic arthropathy, at the site of a failed arthrodesis, and at the site of an unstable delayed union or non-union.