Comparison of continuously collected urines from the two normal kidneys and some effects of unilateral denervation.
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To determine whether there is a delay between the appearance of anti-HIV in serum/plasma and its detection in saliva and urine, salivary and urine specimens were collected from nine individuals who, on the basis of increasing IgG anti-HIV reactivity, Western blot band patterns and presence of strong IgM anti-HIV reactivity in their serum specimens, were believed to have recently become anti-HIV-positive. Serum from 8 of these patients and 3 commercial panels of plasma specimens collected during seroconversion were diluted to mimic the low immunoglobulin concentrations present in saliva and urine and tested in Wellcozyme HIV 1 + 2 GACELISA and four commercial EIAs intended for testing serum specimens. The 9 pairs of saliva and urine specimens were collected between 4 and 43 days (median 24 days) after the first evidence of seroconversion. All were reactive by Wellcozyme HIV 1 + 2 GACELISA and gave optical density/cut off (OD/CO) ratios in the range 3.8 to 9.8 (median 5.2) for dribbled saliva and 2.4 to 10.1 (median 6.3) for urine. Salivary specimens taken with commercial collection devices gave OD/CO ratios in the range 1.6 to 10.6 (median 5.9). In the serum/plasma specimens Wellcozyme HIV 1 + 2 GACELISA detected anti-HIV at higher dilutions than the other assays, often with a 100-fold or more difference. Saliva and urine specimens were all strongly reactive by Wellcozyme HIV 1 + 2 GACELISA. We therefore predict that it would first detect anti-HIV in salivary and urine specimens at about the same time as it becomes detectable in serum/plasma but that other commercial EIAs would not.
A study of the urinary concentration of fentanyl (F) and its major metabolite norfentanyl (NF) in chronic pain patients treated with the Duragesic continuous release transdermal patches is presented. These patches are available in 10, 20, 30, and 40 cm(2) sizes releasing 25, 50, 75, and 100 microg/h F, respectively. F is rapidly and extensively metabolized, with NF as the major metabolite. Five hundred-forty six random urine specimens were collected from chronic pain patients wearing 25, 50, 75, or 100 ug F transdermal patches. Urine specimens were collected from hours after application to several days later after continuous F release. Each specimen was analyzed for F, NF, creatinine, and pH. Additionally, each was screened by enzyme immunoassay for the following: amphetamines, barbiturates, benzodiazepines, cocaine metabolite, methadone, phencyclidine, d-propoxyphene, opiates, and marijuana metabolites. All positive screening results were confirmed by gas chromatography-mass spectrometry (GC-MS). F and NF were isolated from urine by solid-phase extraction then identified and quantified by GC-MS in SIM mode. The LODs and LOQs for F and NF were 3 ng/mL, respectively. The results of F and NF analysis of urine form those wearing 25-microg patches (N = 142) was mean F, 47 ng/mL with a range of 0 to 983 ng/mL, and 97% of the specimens contained < 200 ng/mL and mean NF, 175 ng/mL with a range of 0-980 ng/mL, while 95% of the specimens contained < 400 ng/mL. The results of F and NF analysis of urine form those wearing 50 microg patches (N = 184) was: mean F, 74 ng/mL with a range of 0 to 589 ng/mL, and 92% of the specimens contained < 200 ng/mL and mean NF, 257 ng/mL with a range of 0-2200 ng/mL, and 98% of the specimens contained < 1000 ng/mL. The results of F and NF analysis of urine form those wearing 75 microg patches (N = 85) was mean F, 107 ng/mL with a range of 0 to 1280 ng/mL, and 98% of the specimens contained < 400 ng/mL and mean NF, 328 ng/mL with a range of 0-5630 ng/mL, and 99% of the specimens contained < 1000 ng/mL. The results of F and NF analysis of urine form those wearing 100 ug patches (N = 135) was mean F, 100 ng/mL with a range of 0 to 1080 ng/mL, while 96% of the specimens contained < 400 ng/mL and mean NF, 373 ng/mL with a range of 0-5730 ng/mL, and 95% of the specimens contained < 1000 ng/mL. The incidence of other drugs detected as a percentage the specimens was opiates, 48%, benzodiazepines, 43%; barbiturates, 3%; methadone, 4%; marijuana metabolite, 3%; and cocaine metabolite, 1%. With the exception of F and/or NF, no other drugs were detected in 25% of the specimens. These data demonstrate the wide variation in concentrations of F and NF in random urine specimens following application of Duragesic patches. However, these values obtained during therapeutic use far exceed concentrations previously reported in fatal poisoning. In general, one may expect to find urine NF concentrations 3-4 times higher than those of F.
OBJECTIVE: In a previous study, elevated urine antibody levels in institutionalized subjects with asymptomatic bacteriuria were associated with decreased survival. This study was undertaken to confirm the previous observation in a prospective study in a larger cohort and to explore selected other variables that may be associated with survival. DESIGN: A prospective, 24-month, observational cohort study. SETTING: Three large nursing homes in Winnipeg, Manitoba. PARTICIPANTS: Permanent residents were identified by initial screening urine cultures and subjects with bacteriuria were enrolled. The median age of subjects was 76 years, 51% were women, and the median duration of residence before enrollment was 26 months. Subjects were highly functionally impaired. MEASUREMENTS: Monthly urine specimens were collected for culture, leukocyte count, and urine antibody. Serum specimens for antibody to uropathogens and IL6 were obtained at enrollment and every 6 months. Anthroporphometric tests of nutritional status and functional and mental status were also measured every 6 months. Residents were stratified as having elevated or not elevated urine antibody, based on the initial urine specimen. The mean urine antibody for all of each subject's specimens was also calculated, and subjects were stratified as low, intermediate, or elevated urine antibody. Outcomes measured included mortality, infection and antibiotic use, and functional, mental, and nutritional decline. RESULTS: Ninety-eight bacteriuric subjects were enrolled in the study; 34 (35%) had elevated urine antibody and 64 (65%) had not elevated urine antibody. The two groups did not differ in demographic features, co-morbidities, functional status, medication use, or infecting organisms. Survival was significantly (P < .001) poorer in the group with elevated urine antibody. At 24 months, 35% of subjects with an elevated urine antibody were alive compared with 75% with a low urine antibody level. This survival difference was consistent when the two groups were stratified by sex, institution, and presence of a chronic indwelling catheter. Subjects with elevated urine antibody had no evidence for accelerated functional or nutritional decline during the study period compared with the group with low urine antibody. These subjects did, however, have an increased incidence of episodes of symptomatic urinary infection and infections at non-urinary sites. CONCLUSIONS: Older, bacteriuric, institutionalized subjects with elevated urine antibody had decreased survival rates compared with subjects with lower urine antibody levels. There is no clinical evidence to support accelerated decline caused by chronic infection to explain this observation. Urine antibody may be a marker for immune dysregulation, which precedes death in older impaired subjects.
To assess the appropriateness of a single measurement of urinary 6-sulfatoxymelatonin (aMT6S) as a marker for long-term exposure to endogenous melatonin in epidemiological studies, we examined the reproducibility of aMT6S in first morning urine voids collected from 40 postmenopausal women. Urine specimens were collected on three different occasions, and the mean time between the first and the third urine sample was 5.1 years. Urinary aMT6S levels were measured by radioimmunoassay and adjusted for creatinine. The intraclass correlation for aMT6S adjusted for creatinine was 0.56 (95% confidence interval, 0.39-0.73). The classification of aMT6S concentrations in first morning voids from postmenopausal women appears to be sufficiently reproducible to justify its use as a marker for long-term exposure to melatonin in epidemiological studies.
The objective of this study was to determine whether the method of urine collection impacts the adequacy and cell counts of cytology specimens in a low-risk population. Voided, post-cystometrogram (CMG), and bladder irrigant specimens were collected and evaluated for cytologic adequacy and average cell count by a single cytopathologist masked to the source of each sample. Data were analyzed to detect differences in specimen adequacy and cell counts based on method of collection. Both the voided and post-CMG specimens (97.3%, 93.7% respectively) were significantly more likely to be adequate compared to the bladder irrigant specimen (11.7%, p < 0.0001). The spontaneously voided specimen (211.4 +/- 100.1) had significantly higher cell counts than both the post-CMG specimen (85.9 +/- 86.6) and the cystoscopy specimen (6.4 +/- 19.6, p < 0.0001). In a multivariate linear model, collection method and specimen adequacy were associated with increased cell count/hpf (p < 0.001), as was the presence of hematuria on urine dipstick (p = 0.03). No cytologic abnormalities were diagnosed. Whereas both spontaneously voided and post-CMG specimens were consistently adequate for interpretation, spontaneous voided specimens were optimal with regard to maximizing cell count/hpf.
The dose-response relationship between cadmium (Cd) exposure and renal dysfunction, as measured by urinary Cd and metallothoinein (MT), was evaluated in a population living in the Kakehashi River basin, a Cd-polluted area in Japan. Morning urine specimens were collected from 1397 men and 1713 women who were 50 years or older. In addition, urine specimens were collected from a control population consisting of 110 men and 130 women. The 97.5% upper limits for MT in the control population were used to determine the prevalence rates for MT-uria at various urinary Cd concentrations. Probit linear regression analysis showed significant dose-response relationships between MT and Cd. In the control population, prevalence rates of MT-uria for men and women were 1.8 and 3.1%, respectively. Based on the prevalence rates of MT-uria in the control population, the upper limits for the urinary Cd concentrations were calculated from the slopes of the regression lines to be 4.2 and 4.8 micrograms/g creatinine for men and women, respectively. These values, which are similar to those reported previously using urinary beta 2-microglobulin as the indicator, may be of use in establishing the biological threshold, i.e. maximum allowable concentration, for urinary Cd in the environmentally exposed Japanese population.
The subchronic toxicity of chloral hydrate, a disinfection byproduct, was studied in rats following 13 weeks of drinking water exposure. Male (262 +/- 10 g) and female (190 +/- 8 g) Sprague-Dawley rats, ten animals per group, were administered chloral hydrate via drinking water at 0.2, 2, 20 and 200 ppm. Control animals received distilled water only. Gross and microscopic examinations, serum chemistry, hematology, biochemical analysis, neurogenic amine analysis and serum trichloroacetic acid (TCA) analysis were performed at the end of the treatment period. Bronchoalveolar fluids were collected at necropsy and urine specimens were collected at weeks 2, 6 and 12 for biochemical analysis. No treatment-related changes in food and water intakes or body weight gains were observed. There were no significant changes in the weights of major organs. Except for a mild degree of vacuolation within the myelin sheath of the optic nerves in the highest dose males, there were no notable histological changes in the tissues examined. Statistically significant treatment-related effects were biochemical in nature, with the most pronounced being increased liver catalase activity in male rats starting at 2 ppm. Liver aldehyde dehydrogenase (ALDH) was significantly depressed, whereas liver aniline hydroxylase activity was significantly elevated in both males and females receiving the highest dose. A dose-related increase in serum TCA was detected in both males and females starting at 2 ppm. An in vitro study of liver ALDH confirmed that chloral hydrate was a potent inhibitor, with an IC(50) of 8 micro M, whereas TCA was weakly inhibitory and trichloroethanol was without effect. Analysis of brain biogenic amines was conducted on a limited number (n = 5) of male rats in the control and high dose groups, and no significant treatment-related changes were detected. Taking into account the effect on the myelin sheath of male rats and the effects on liver ALDH and aniline hydroxylase of both males and females at the highest dose level, the no-observed-effect level (NOEL) was determined to be 20 ppm or 1.89 mg kg(-1) day(-1) in males and 2.53 mg kg(-1) day(-1) in females. This NOEL is ca. 1000-fold higher than the highest concentration of chloral hydrate reported in the municipal water supply.
OBJECTIVE: To examine the age dependency of the urinary para-aminobenzoic acid (PABA) excretion, and if a delayed PABA excretion can be overcome by advancing intake schedule; and to examine the recovery of PABA in fractionated urinary samples collected during 24 h after single and repeated doses of PABA. DESIGN: Cross-over study with subjects randomized to start with recommended schedule of PABA administration (80 mg at 08:00, 12:00 and 18:00; PABA18) and then an advanced schedule (80 mg at 08:00, 12:00 and 15:00; PABA15) or vice versa. One subgroup of eight subjects collected individual urine specimens for 24 h after a morning dose of 80 mg of PABA, and another subgroup of 10 subjects collected individual urine specimens for 24 h after ingestion of 80 mg of PABA three times at mealtimes. SUBJECTS: Employees and relatives from the Danish Food Administration. SETTING: Ninety-nine healthy volunteers (61 females and 38 males) aged 30-91 y. RESULTS: Linear regressions for PABA15 and PABA18 demonstrate significantly less recovery with age (PABA15: r(2)=0.1784, P=0.0002; PABA18: r(2)=0.1273, P=0.0019). Linear regression of DeltaPABA (PABA15-PABA18) with age showed the best fit line to be horizontal (slope -0.0066, P=0.89; 95% CI -0.1046, 0.0915) and with a Y-intercept not significantly different from 0 (1.575; 95% CI -4.176, 7.326). In this population the lower limit for complete 24 h urine collection was 79.2%. After a single dosage of 80 mg PABA 70-85% was recovered after 8 h. Within 16 h after ingestion of 240 mg PABA at recommended hours the lowest acceptable recovery (78.1%) was reached. CONCLUSION: There is a gradual decline of PABA recovery with age that cannot be overcome by advancing the dosage schedule. Because of a lower delimiting PABA recovery for the elderly, some 24 h collections in this age group will be rejected unjustly (false-negatives). Also, with the currently recommended dosage schedule (PABA taken with the main meals) the risk of false-positive 24 h urine collections prevails. With refinement of the PABA test procedure, ie employing a specific analytical method and age-dependent cut-off values, the test may achieve a higher specificity and sensitivity.
An immunoradiometric assay for free beta-human chorionic gonadotropin (F beta hCG) is now available. Measurement of serum F beta hCG has been shown to be valuable for the diagnosis of trophoblastic disease and for screening Down's syndrome pregnancies. Urine specimens may be preferable to blood samples since collection of urine specimens usually are less inconvenient to patients than venipuncture. We have evaluated whether the immunoradiometric assay can be applicable to urine samples. The assay was sensitive and precise. When urine samples were diluted 4-fold or more, the diluted samples gave quantitative values, and recovery of beta hCG added to urine samples was satisfactory. Creatinine corrected urinary F beta hCG levels correlated with serum F beta hCG levels. Thus, the immunoradiometric assay was considered to be applicable to urine samples. Serum F beta hCG to hCG ratio has been reported to be important to distinguish among normal pregnancies, hydatidiform mole and choriocarcinoma. However, urinary F beta hCG to hCG ratio did not significantly correlate with serum F beta hCG to hCG ratio. And therefore, the clinical value of urinary F beta hCG to hCG ratio should be further investigated.
We intensively studied 30 women attempting pregnancy in order to lay groundwork for larger studies of early pregnancy loss. These women collected first morning urine specimens for up to 6 months after discontinuing use of birth control. Urine specimens were successfully collected for 98% of the woman-days in the study. Three assays for human chorionic gonadotropin (hCG) were performed on each urine specimen. An immunoradiometric assay (IRMA) specific to the carboxyterminal peptide of the hCG beta-chain proved to be more sensitive and more specific than two radioimmunoassays (RIAs). Using the IRMA, we found four cases in which hCG rose and fell over successive days, consistent with early pregnancy loss. For three of these four cases, the level of hCG was too low to be detectable with the RIAs. Among the control group of five women with tubal ligations, there was no detectable hCG above threshold with the IRMA. Thus, the enhanced sensitivity and specificity of the IRMA allows very early pregnancy losses to be identified that would otherwise be undetectable. Furthermore, its effectiveness with small quantities of first morning urine makes the IRMA a useful tool for epidemiologic studies.
OBJECTIVE: To estimate the optimal relative light unit ratio, as a measure of viral load, of the Hybrid Capture II human papillomavirus (HPV) test in self-collected specimens for detecting cervical intraepithelial neoplasia (CIN). METHODS: Two hundred women referred for colposcopy with abnormal cytologic, self-collected vaginal and vulvar swabs and urine for HPV testing. The receiver operating characteristic (ROC) curve method was used to estimate optimal cutoffs for the Hybrid Capture II test. The reference standard was colposcopy, with directed biopsy as required. RESULTS: The estimated optimal cutoffs of the relative light unit ratio for detecting CIN 2 or higher for urine, vulvar, and vaginal samples gave sensitivities of 72.4%, 82.8%, and 89.0% and specificities of 57.0%, 52.1%, and 55.9%, respectively. At the manufacturer's recommended 1.0 cutoff, sensitivities were 44.8%, 62.1%, and 86.2% for urine, vulvar, and vaginal samples, with specificities of 69.7%, 62.7%, and 53.5%, respectively. The likelihood ratios (likelihood of being truly positive after a positive test result) were similar for the optimal and the 1.0 cutoff. CONCLUSIONS: The ROC curve methods did not improve the overall diagnostic accuracy of the Hybrid Capture II test compared with the 1.0 relative light unit ratio cutoff.
Review of scientific literature shows that ingestion of poppy seed containing products can result in a positive urinalysis test for opiates. In many cases the amount of seeds ingested is unrealistically high or is not specified. This study is designed to correlate the amount of seeds ingested with the urinary concentration of total morphine as a function of time. Two males and two females were involved in all four protocols, which were separated by at least one week. Subjects ingested one, two, or three poppy seed rolls, each containing 2 g of Australian seeds (108 micrograms morphine/g seed) in three protocols. In the fourth protocol subjects ingested two rolls per day for four consecutive days. Urine specimens were collected for 48 h after ingestion, analyzed by RIA, EMIT, and TDx, and selected samples were confirmed by GC/MS. The data show that the highest concentrations of total morphine in urine were found 3-8 h after ingestion or in the first-void samples. Of the 264 samples collected, there were only 16 specimens that exceeded 300 ng/mL by any of the methods used for analysis with only three samples exceeding 400 ng/mL by GC/MS (406, 611, and 954 ng/mL). In all cases, the total opiates level was less than 150 ng/mL 24 h after ingestion. Following these studies, one of the subjects ingested a poppy seed cake containing 15 g seed obtained from a bakery which analyzed for 169 micrograms morphine/g seed. Urine specimens were collected over 48 h, and all specimens were analyzed by GC/MS.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: This study aimed to clarify the iodine deficiency status in the Semipalatinsk region that has been contaminated by radioactive fallout from nuclear testing during the period of the former USSR. DESIGN: Based on the Japan-Kazakstan joint project of adult cancer screening around the Semipalatinsk Nuclear Testing Site (SNTS), from May to October 2002 spot urine specimens were collected at random in each village. Separately, children aged 5-15 years from around the SNTS were chosen at random and spot urine specimens were collected from them. SETTING: Area contaminated by radioactive fallout around the SNTS, Republic of Kazakstan. SUBJECTS: A total of 2609 adults aged >40 years from 16 settlements in three regions and one city, and 298 children aged 5-15 years from two regions and one city. RESULTS: Median urinary iodine concentrations of adults and children in all regions were in the range of 116.0-381.7 and 127.7-183.0 microg l(-1), respectively. The highest prevalence of values <50 microg l(-1) (14.1%) did not exceed 20%. Distributions within each group, adults and children, showed almost the same pattern, except for one region where more than 50% of adults had urinary iodine concentration >100 microg l(-1). CONCLUSIONS: In agreement with our previous studies, the urinary iodine concentration data showed no clear evidence of iodine deficiency around the SNTS. Kazakstan is geographically and nutritionally at moderate risk of iodine deficiency disorders without fortification or iodine replacement by iodised salt. The socio-medical prophylaxis against iodine deficiency has been successfully maintained in East Kazakstan.
A group of 14 subjects, who had been identified from 261 volunteers in a 1-week screen as being able to metabolize the sweetener cyclamate to cyclohexylamine (>0.2% of a daily dose), and 31 nonconverters (<0.2% metabolism) were given calcium cyclamate tablets (equivalent to 250 mg cyclamic acid, 3 times daily) for a period of 13 weeks. The metabolism of cyclamate to cyclohexylamine was determined using twice-weekly timed (3 h) urine collections during week 1-3 and 7-13. Urine specimens were collected on all other study days to investigate day-to-day fluctuations in cyclohexylamine excretion. Analyses of the twice weekly timed urine collections showed that subjects recruited as nonconverters essentially remained nonconverters. Of the converters, three showed consistently low metabolism, five showed erratic metabolism, five showed low metabolism initially, which increased during the latter part of the study, and one subject showed consistently high metabolism throughout the study. Analysis of the day-to-day urine specimens showed marked intrasubject variability. The plasma concentrations of cyclohexylamine measured on weeks 1-3 and 7-13 reflected the urine profiles. The highest individual long-term average steady-state excretion values based on the 3-h urine collections and daily samples were 21%, 23%, 25%, 29%, 34%, and 38%. The maximum % metabolism detected in the high converters occasionally reached the value of 60% reported in previous short-term studies, but this high activity was not maintained, and was followed by periods of lower metabolism. The results of this metabolism study support an acceptable daily intake (ADI) of 0-11 mg/kg body weight per day.
Twenty-four hour urine specimens were collected from caged domestic cats using modified rubber dish pans. This simple method provided an uncontaminated specimen, total daily urine output and required no training of the animals.
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In the multicenter, randomized, placebo-controlled trial of alternate-day injections of recombinant interferon beta-1b in relapsing-remitting multiple sclerosis (MS), urine specimens were collected periodically from all patients (n = 64) in two of the clinical test sites over the 2 years of the study. Urine specimens were also collected over two consecutive 24-hour periods from 43 patients from a third center. Urine samples were assayed for their content of myelin basic protein-like material (MBPLM), the level of which was correlated with clinical changes, cranial magnetic resonance imaging results, and the development of progressive disease. Concordant changes in creatinine values affected some of the relationships of MBPLM. The level of urinary MBPLM correlated with a chronic progressive course and with the number of lesions and the total lesion area on cranial magnetic resonance images. A rise in the level of urinary MBPLM appeared to antedate the clinical transition from a relapsing-remitting to a chronic progressive course. By chance, the randomized entry of patients led to significant differences in urinary MBPLM levels among the three treatment groups, thus precluding correlation studies of treatment effects. However, the patient group from which 24-hour specimens were collected showed that the patients with relapsing-remitting MS changing to a chronic progressive course, and more specifically, those patients with chronic progressive MS receiving placebo, had the highest values of urinary MBPLM. These findings indicate that urinary MBPLM may offer an objective test and possibly serve as a surrogate marker for detecting or predicting the failure of remission or the transition to a progressive phase of MS.