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Drugs in sport. A report of laboratory investigations into the prevalence of their use in South Africa.

Screening procedures utilizing two-dimensional thin-layer chromatography, gas-liquid chromatography and gas chromatography-mass spectrometry were carried out in an attempt to detect stimulant drugs in urine specimens collected from competitors in three major sporting events held during 1983. Drugs classified as forbidden stimulants by the International Olympics Committee were detected in 4% of the specimens collected from competitors in the South African Athletics Championships and in 28% of the specimens collected from competitors in the 1983 Rapport Cycling Tour, while none were detected in specimens collected from competitors in the South African Senior Swimming Championships.

Bicycling↗

[Urinary excretion of rifampicin in kidney failure when administered alone or together with isoniazid].

Rifampicin excretion with urine and its plasma levels were studied in 46 patients with nephrophthisis treated with rifampicin alone or in combination with isoniazid in doses of 8--10 mg/kg bw with regard to the degree of renal insufficiency. It was shown that excretion of rifampicin with urine decreased with progression of renal insufficiency and had no effect on its plasma levels. The combined use of isoniazid and rifampicin in a single dose was accompanied by a decrease in the latter's excretion with urine and different changes in its plasma concentration. The use of the two drugs for 4--6 weeks resulted in a further decrease in rifampicin excretion with urine not dependent on renal function and in decreased plasma levels of the antibiotic in 1/3 of patients. The findings indicate that the use of rifampicin in a dose less than 10 mg/kg of the body weight in patients with chronic renal insufficiency is not advisable. The absence of rifampicin in the urine specimens collected during the first hours on the 2nd day after its single use or its use for 4--6 weeks indicate that rifampicin does not accumulate in patients with renal insufficiency.

Administration, Oral↗

Urinary tryptophan metabolites and cancer of the bladder in humans.

Urinary excretion of six aromatic amine metabolites of tryptophan was compared between a group of 30 patients with bladder cancer and a group of 33 controls selected from the general population of the study area. Measurements were based on a single overnight urine specimen collected at home by each subject, without a "loading" does of L-tryptophan. For each metabolite, both the distribution and the mean amount excreted were nearly identical for cases and controls. The small cases-control differences in mean values were virtually unchanged by adjustment for age, sex, and smoking status. Generally, excretion levels were higher for females than for males. Excretion levels also tended to be higher for older than for younger subjects and for smokers compared to nonsmokers. However, most of these differences also were small.

Adult↗

Urinary p-aminobenzoic acid determined in the pancreatic function test by liquid chromatography, with electrochemical detection.

We describe a liquid-chromatographic procedure for determining urinary p-aminobenzoic acid (PABA) in the exocrine pancreatic function test. The urine specimen, collected for 6 h after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid, is hydrolyzed in 4 mol/L NaOH containing m-hydroxybenzoic acid as internal standard, to free PABA metabolites, then diluted and injected into the chromatograph. PABA and the internal standard are eluted from a reversed-phase C18 column with phosphate buffer (0.2 mol/L, pH 3.5)/acetonitrile, 87.5/12.5 (by vol), and detected with an electrochemical detector at +1100 mV. Urinary PABA concentration as measured by this method agreed well with that by colorimetry involving p-dimethylaminocinnamaldehyde. The present procedure is specific for PABA, precise, and fairly rapid. We hope that the present method will minimize instances of interference from drugs, which cannot be avoided in the colorimetric method.

4-Aminobenzoic Acid↗

Urine cytology. Part I: urinary tract cytology.

Urinary tract cytology is an excellent means of detecting urinary tract neoplasia. It is not a good localizing technique but is an exceptionally useful diagnostic tool for monitoring high-risk patients. The closer the lesion is to the collecting point, the higher the degree of diagnostic accuracy. Thus, cells from a bladder cancer are more frequently seen than malignant cells from the ureter or renal pelvis. Properly collected urine specimens examined by qualified cytologists can also aid in the diagnosis of infections and inflammatory diseases.

Epithelial Cells↗

[Histopathological assessment of renal biopsy specimens of subjects with urine abnormality].

Between April 1985 and April 1992, 25,672 men (age 47 +/- 9 years, mean +/- SD) and 9,791 women (48 +/- 9 years) underwent mass urinalysis in the Center for Adult Complete Physical Examination in our hospital. The results revealed proteinuria in 6.3% of the men and 4.4% of the women and hematuria in 17.4% of the men and 37.8% of the women. Thirty-five subjects with asymptomatic persistent proteinuria and/or hematuria identified as a result of follow-up testing by the nephrologists at our hospital underwent renal biopsy. All of the biopsy specimens obtained were examined by light microscopy, fluorescence microscopy and electron microscopy. Histopathological findings in the biopsy specimens from these 35 subjects were as follows: One case (3%) of chronic pyelonephritis, 11 cases (31%) of IgA nephropathy, 4 cases (11%) of IgA nephropathy (severe type), 5 cases (14%) of membranous nephropathy, 4 cases (11%) of thin basement membrane disease (TMD), 7 cases (28%) of benign nephrosclerosis and 3 cases (9%) of minor glomerular abnormality. Light microscopy, fluorescence microscopy and electron microscopy for histopathological assessment of renal specimens, especially for the diagnosis of TDM, which was not uncommon, were indispensable tools in our study. Moreover, it is essential for proteinuria and hematuria to be tested simultaneously using the same standard method in all the urine specimens collected.

Adult↗

Assessment of cocaine use with quantitative urinalysis and estimation of new uses.

Qualitative urinalysis methods of monitoring cocaine use may over-detect frequency of use, possibly decreasing the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in non-treatment-seeking subjects (n = 5) and a cocaine treatment trial (n = 37) were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria ('New Use' rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self-reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use.

Adolescent↗

Which bacteria are found in Belgian women with uncomplicated urinary tract infections in primary health care, and what is their susceptibility pattern anno 95-96?

Dysuria is a frequent reason for encounter in general practice and also gynaecologists and urologists will be frequently confronted with it. In female patients 1/2 to 2/3 of dysuric episodes are due to urinary tract infections. In nearly all cases therapy is started before the results of a culture is available. Therefore it is very important to know which bacteria are most prevalent in the treated population, and what their susceptibility pattern is . Because most available information is based on retrospective data issued from very mixed populations, we performed a prospective study including the most frequently involved population: symptomatic adult women without any symptom of complicated UTI. Among 279 urine specimens collected in general practices, 164 were positive (59%). The most frequent micro-organism found was E. coli (78%), followed by S. saprophyticus (9%) and Proteus spp. (4%). In the 15 remaining specimens, 8 different bacterial species were found. Overall resistance to ampicillin was 30%, to cotrimoxazole 14%, to nitrofurantoin 7%, to fluoroquinolones 1%. The E.coli resistance to ampicillin was 27%, to co-trimoxazole 17%, to nitrofurantoin 1% and to fluoroquinolones 1%. In this population the same bacteria, in the same proportion, are found as in earlier studies in other countries. The susceptibility pattern confirms a substantial resistance level to ampicillin and co-trimoxazole. On the contrary, resistance to nitrofurantoin and fluoroquinolones is negligible. Resistance data from Belgian regional laboratories in their outpatient population were significantly different from ours.

Adolescent↗

Collecting midstream specimens of urine--the research base.

The study reported here, which is based on an undergraduate dissertation, analyses the content of medical and nursing articles published between 1956 and 1989 which consider the collection of mid-stream specimens of urine (MSSUs). Subjective or qualitative and objective or quantitative content analyses were performed. A large disparity was discovered between the results of the two methods of analysis, implying that this research base cannot be translated into recommendations for collecting MSSUs.

Adolescent↗

Intensive surveillance for cocaine use in obstetric patients.

OBJECTIVE: To determine the value of intensive surveillance for cocaine use in pregnancy and also determine the prevalence of cocaine use in our institution. METHODS: Among 124 consecutive new obstetrical clinic patients, urine specimens were collected anonymously at the first prenatal visit, in each subsequent trimester of pregnancy, and on labor and delivery. Corresponding newborn urine and meconium were also collected for these patients. 324 urine specimens and 49 meconium specimens were obtained. A local private group also collected first prenatal visit urine from an additional 104 patients. Urine specimens were analyzed for cocaine metabolites by fluorescent polarization immunoassay with confirmation of positive results by gas chromatography/mass spectrophotometry. RESULTS: One clinic patient had a positive cocaine screen. All other urine and meconium screens were negative. CONCLUSION: Intensive surveillance did not increase the detection rate for cocaine abuse in our obstetric population. We also found that the prevalence of cocaine abuse among obstetrical patients at our institution is low (< 1%). These data reconfirm that resource allocation for drug treatment centers should be based on prevalence data specific to an area or institution.

Cocaine↗

A method for the determination of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in urine using high performance liquid chromatography with electrochemical detection.

11-Nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) was isolated using solid phase extraction and identified with high performance liquid chromatography (HPLC) with electrochemical detection (EC). HPLC/EC was compared to an established HPLC procedure using ultraviolet (UV) detection. Statistical analysis revealed good precision, linearity, and correlation between the HPLC/EC and HPLC/UV methods. Within-run and between-run precision for the HPLC/EC vs. HPLC/UV analyses yielded coefficients of variation of 4.1 vs. 6.7% and 8.3 vs. 10.9%, respectively. Standard curves over a range of 20 to 160 ng/mL of THC-COOH in fortified urine on four separate analytical runs yielded correlation coefficients of greater than 0.99 for each method. Quantitative results from 15 positive urine specimens also compared favorably between the two methods (r = 0.9923). Using an immunoassay screening technique with confirmation by HPLC/UV and high efficiency thin layer chromatography (HETLC), further evaluation of the HPLC/EC method was achieved by examining 50 cannabinoid positive and 50 cannabinoid negative clinical urine specimens and 500 sequentially collected postmortem urine specimens.

Chromatography, High Pressure Liquid↗

Comparison between blood and urinary toluene as biomarkers of exposure to toluene.

OBJECTIVES: To compare blood toluene (TOL-B) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene, and to set a suitable procedure for collection and handling of specimens. METHOD: An assay based on headspace solid-phase microextraction (SPME) was used both for the determination of toluene urine/air partition coefficient (lambdaurine/air) and for the biological monitoring of exposure to toluene in 31 workers (group A) and in 116 non-occupationally exposed subjects (group B). Environmental toluene (TOL-A) was sampled during the work shift (group A) or during the 24 h before specimen collection (group B). Blood and urine specimens were collected at the end of the shift (group A) or in the morning (group B) and toluene was measured. RESULTS: Toluene lambdaurine/air was 3.3 +/- 0.9. Based on the specimen/air partition coefficient, it was calculated that the vial in which the sample is collected had to be filled up to 85% of its volume with urine and 50% with blood in order to limit the loss of toluene in the air above the specimen to less than 5%. Environmental and biological monitoring of workers showed that the median personal exposure to toluene (TOL-A) during the work-shift was 80 mg/m3, the corresponding TOL-B was 82 microg/l and TOL-U was 13 microg/l. Personal exposure to toluene in environmentally exposed subjects was 0.05 mg/m3, TOL-B was 0.36 microg/l and TOL-U was 0.20 microg/l. A significant correlation (P < 0.05) was observed between TOL-B or TOL-U and TOL-A (Pearson's r = 0.782 and 0.754) in workers, but not in controls. A significant correlation was found between TOL-U and TOL-B both in workers and in controls (r = 0.845 and 0.681). CONCLUSION: The comparative evaluation of TOL-B and TOL-U showed that they can be considered to be equivalent biomarkers as regards their capacity to distinguish workers and controls and to correlate with exposure. However, considering that TOL-U does not require an invasive specimen collection, it appears to be a more convenient tool for the biological monitoring of exposure to toluene.

Adult↗

Chronic urinary tract infection in dogs: induction by inoculation with bacteria via percutaneous nephropyelostomy.

Dogs were inoculated via percutaneous nephropyelostomy with bacteria isolated from canine patients with urinary tract infections (4 dogs were inoculated with Escherichia coli, 2 were inoculated with Proteus mirabilis, and 1 was inoculated with coagulase-positive staphylococci). At approximately monthly intervals after bacterial inoculation, bladder urine specimens were collected via antepubic cystocentesis, and renal pelvic urine specimens were collected via percutaneous nephropyelocentesis. Dogs were euthanatized between 89 and 294 days after bacterial inoculation. Extensive microscopic examination was conducted on the urinary tract of each dog. The dogs did not develop any of the common clinical signs of urinary tract infections (ie, increased frequency of urination, fever, craniodorsal abdominal [renal] pain, or malaise). Inflammation in the lower urinary tract of the dogs was more severe than that in the kidneys. Although pyelitis was present, extension into the outer medulla and renal cortex seemed to be confined to nephropyelostomy tracts. The most severe bladder lesion was found in the dog that developed cystic calculi after inoculation with coagulase-positive staphylococci.

Animals↗

Urinary and blood manganese in occupationally nonexposed populations and in manual metal arc welders of mild steel.

To obtain reference values for blood and serum manganese levels, blood specimens were collected from 29 men and 36 women. Mn in blood showed a normal distribution; its upper 97.5% limit in blood was 0.38 mumol/l. Mn in serum showed a skewed distribution, which did not differ from the normal one after logarithmic transformation. The respective reference limit was 19 nmol/l. In both specimens, the levels of Mn were significantly lower in men than in women. To obtain reference values for Mn in urine, midday urine specimens were collected from 58 men and 96 women. Mn in urine also showed a skewed distribution, and the upper 97.5% limit was 38 nmol/l. The levels of Mn in blood and urine were statistically significantly higher in manual metal arc (MMA) welders of mild steel (MS) than in the reference populations. Five MMA/MS welders were subjected to a further study in which the ambient intramask Mn levels and urinary Mn excretion were monitored throughout a full working week. For two welders the correlation of Mn in urine specimens voided in the afternoon was good with the before noon Mn concentrations in the hygienic measurements; for the rest the correlation was minimal. Mn in diurnal urine specimens collected in six portions showed fluctuation if specific gravity or creatinine in urine was used to standardize for the urinary flow, but it was less evident for urinary Mn excretion rate. Our results seem to indicate that the measurement of Mn in urine or blood may be used for monitoring Mn exposure in MMA/MS welders only at the group level.

Adolescent↗

Comparison of tampon and urine as self-administered methods of specimen collection in the detection of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in women.

Self-administered sampling techniques for the detection of sexually transmitted diseases (STDs) are particularly useful due to their ease of collection and better patient compliance. Urine specimens, and recently tampons, have been described as methods of specimen collection for the detection of some STDs in women. In this study, 660 women had both first-void urine (FVU) and tampon specimens analysed by polymerase chain reaction (PCR) for the detection of Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis. Overall 6.5%, 10.1% and 17.9% of urine samples were positive whereas 7%, 21.2% and 22% of tampon specimens were positive for C. trachomatis, N. gonorrhoeae and T. vaginalis respectively. Tampon-collected specimens tested by PCR were more sensitive than urine specimens for the detection of N. gonorrhoeae and T. vaginalis (P < 0.001) and equally sensitive for the detection of C. trachomatis (P=0.45).

Animals↗

The Danish Breast Cancer Group (DBCG) biochemical tumor marker program.

One hundred and thirty-three high-risk breast cancer patients entered the DBCG (Danish Breast Cancer Cooperative Group) tumor marker program between May 1978 and June 1980. Eleven were excluded from the DBCG protocol and 23 left the program prematurely. The remaining patients were seen at the clinical laboratory once a month during the first year and every third month during the second and third year following mastectomy. Blood and urine specimens were collected and plasma, serum and urine specimens stored at -80 degrees C. The purposes of the program were 1) to collect a biological material which may later be used to assess the usefulness of biochemical markers for the prediction of recurrence and 2) to develop statistical time series models suitable for this assessment. Such a model is presented and its application for the assessment of the usefulness of 14 common tumor markers reviewed. Only P-CEA proved to be of any value but its usefulness was marginal.

Biomarkers, Tumor↗

Competitive binding inhibition enzyme-linked immunosorbent assay that uses the secreted aspartyl proteinase of Candida albicans as an antigenic marker for diagnosis of disseminated candidiasis.

The secreted aspartyl proteinases (Saps) of Candida albicans have been implicated as virulence factors associated with adherence and tissue invasion. The potential use of proteinases as markers of invasive candidiasis led us to develop a competitive binding inhibition enzyme-linked immunosorbent assay (ELISA) to detect Sap in clinical specimens. Daily serum and urine specimens were collected from rabbits that had been immunosuppressed with cyclophosphamide and cortisone acetate and infected intravenously with 10(7) C. albicans blastoconidia. Disseminated infection was confirmed by organ culture and histopathology. Although ELISA inhibition was observed when serum specimens from these rabbits were used, more significant inhibition, which correlated with disease progression, occurred when urine specimens were used. Urine collected as early as 1 day after infection resulted in significant ELISA inhibition (mean inhibition +/- standard error [SE] compared with preinfection control urine, 15.7% +/- 2.7% [P < 0.01]), and inhibition increased on days 2 through 5 (29.4% +/- 4.8% to 44.5% +/- 3.5% [P < 0.001]). Urine specimens from immunosuppressed rabbits infected intravenously with Candida tropicalis, Candida parapsilosis, Candida krusei, Cryptococcus neoformans, Aspergillus fumigatus, or Staphylococcus aureus were negative in the assay despite culture-proven dissemination. Nonimmunosuppressed rabbits receiving oral tetracycline and gentamicin treatment were given 2 x 10(8) C. albicans blastoconidia orally or intraurethrally to establish colonization of the gastrointestinal tract or bladder, respectively, without systemic dissemination; urine specimens from these rabbits also gave negative ELISA results. Dissemination to the kidney and spleen occurred in one rabbit challenged by intragastric inoculation, and urine from this rabbit demonstrated significant inhibition in the ELISA (mean inhibition +/- SE by day 3 after infection, 32.9% +/- 2.7% [P < 0.001]). The overall test sensitivity was 83%, the specificity was 92%, the positive predictive value was 84%, the negative predictive value was 91%, and the efficiency was 89% (166 urine samples from 33 rabbits tested). The specificity, positive predictive value, and efficiency could be increased to 97, 95, and 92%, respectively, if at least two positive test results were required for a true positive designation. The ELISA was sensitive and specific for the detection of Sap in urine specimens from rabbits with disseminated C. albicans infection, discriminated between colonization and invasive disease, reflected disease progression and severity, and has the potential to be a noninvasive means to diagnose disseminated candidiasis.

Animals↗

Urinary excretion profiles of 11-nor-9-carboxy-delta9-tetrahydrocannabinol and 11-hydroxy-delta9-THC: cannabinoid metabolites to creatinine ratio study IV.

The objective of this study was to compare urinary excretion patterns of two cannabinoid metabolites in subjects with a history of chronic marijuana use. The first metabolite analyzed was nor-9-carboxy-delta9-tetrahydrocannabinol (delta9-THC-COOH), the major urinary cannabinoid metabolite that is pharmacologically inactive. The second metabolite 11-OH-delta9-THC is an active cannabinoid metabolite and is not routinely measured. Urine specimens were collected from four subjects on 12-20 occasions > or = 96 h apart in an uncontrolled clinical setting. Creatinine was analyzed in each urine specimen by the colorimetric modified Jaffé reaction on a SYVA 30R biochemical analyzer. All urine specimens analyzed for 11-OH-delta9-THC had screened positive for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/mL) on a SYVA 30R analyzer and submitted for delta9-THC-COOH confirmation by GC-MS (cut-off concentration 15 ng/mL). Eleven-OH-delta9-THC was measured by GC-MS with a cut-off concentration of 3 ng/mL. Both GC-MS methods for cannabinoid metabolites used deuterated internal standards for quantitative analysis. The mean (range) of urinary delta9-THC-COOH concentration was 1153 ng/mL (78.7-2634) with a cut-off of 15 ng/mL. The mean (range) of delta9-THC-COOH/creatinine ratios (ng/mL delta9-THC-COOH/mmol/L creatinine) was 84.1 (8.1-122.1). The mean (range) urinary of 11-OH-delta9-THC concentration was 387.6 ng/mL (11.9-783) with a cut-off of 3 ng/mL, and the mean (range) of 11-OH-delta9-THC/creatinine ratio (ng/mL 11-OH-delta9-THC/mmol/L creatinine) was 29.7 (1.2-40.7). Of the 63 urine specimens submitted for delta9-THC-COOH confirmation by GC-MS, 59/63 urine specimens (94%) were positive for delta9 -THC-COOH and 51/63 (81%) were positive for 11-OH-delta9-THC. Overall, the concentrations of 11-OH-delta9-THC in urine specimens collected > or = 96 h apart were lower than delta9-THC-COOH concentrations in 50/51 of the urine specimens in this population. Further urinary cannabinoid excretion studies are needed to assess whether 11-OH-delta9-THC analyses have a role when assessing previous marijuana or hashish use in chronic users whose urine specimens remain positive for delta9-THC-COOH for an extended period of time after last drug use.

Creatinine↗