Opiates and human chromosome alterations

Methods of monitoring occupational exposure to methanol were investigated in volunteer subjects who had ingested small amounts of methanol. It was confirmed that urinary methanol concentrations accurately reflected those in the blood. This relationship was maintained over a considerable range of concentrations in spite of large variations of urine flow. Concomitant ingestion of ethanolic beverages increased the urinary methanol concentration slightly. Urinary formic acid concentration was too variable to be of value but rate of urinary excretion of formic acid did reflect methanol uptake. The ratio of urinary formic acid to creatinine concentrations (F/C ratio) is a practical monitoring method. However, formic acid elimination rate is reduced by ingestion of ethanolic beverages. Urinary methanol concentration is favoured as a method of monitoring and a concentration of 10 microgram/ml measured at the end of the work shift is suggested as the level above which occupational exposure should be suspected and the appropriate action taken.     

Effects of Bromide Ion and Natural Organic Matter Fractions on the Formation and Speciation of Chlorination By-Products

The impacts of bromide concentration and natural organic matter (NOM) characteristics on the formation and speciation of disinfection by-products (DBPs) in chlorinated NOM fractions were investigated. A total of 20 bulk water NOM fractions with a wide range of specific ultraviolet (UV) absorbance (SUVA254) values were obtained from a source water employing XAD-8 or XAD-4 resin adsorption in completely mixed batch reactors. SUVA was not a good predictor of DBP [trihalomethanes (THMs), haloacetic acids (HAAs), and adsorbable organic halogens (AOX)] formation and speciation. The destruction in the UV254 absorbance from chlorination did not correlate with DBP formation at any bromide level. NOM moieties which do not absorb UV light at 254?nm significantly contributed to DBP formation. Mass balance calculations on halogens using THMs, HAAs, and AOX data indicated that significant amounts of DBPs (>54% of AOX) other than THMs and HAAs were formed in NOM fractions with 60–110?μg/L bromide concentration. The relative occurrence of such other halogenated by-products decreased with increasing bromide concentrations up to 500?μg/L level. NOM in the studied water was more susceptible to the formation of brominated THM species as opposed to brominated HAAs. At constant dissolved organic carbon concentration, chlorine dose and pH, increasing bromide concentrations in NOM fractions increased the total concentrations of DBPs and resulted in a shift toward the formation of brominated species. Further, increasing bromide concentrations increased the spectrum of detected species (i.e., occurrence of all nine HAAs) and provided a competitive advantage to THM and HAA precursors in NOM over precursors of other DBPs.     

Effect of acute water loading on urinary excretion of prostaglandin E in hypertensive patients

To assess the relationship or urine flow to the urinary excretion of prostaglandin E (PGE), urinary excretion of PGE was measured before and after acute water loading (20 ml/kg orally) in patients with hypertension. Water loading promptly increased urinary excretion of PGE as well as urine flow rate and decreased urine osmolality (all p less than 0.001), but did not affect urinary excretions of sodium, potassium and creatinine, plasma renin activity and plasma aldosterone concentration. There was a significant positive correlation between urine flow rate and urinary PGE excretion rate (p less than 0.01). Urinary PGE concentration correlated negatively with urine flow rate when the flow was lower than 5 ml/min (p less than 0.01). Urinary PGE concentration correlated negatively with urine flow rate when the flow was lower than 5 ml/min (p less than 0.01), whereas it did not change when the urine flow rate was larger than 5 ml/min. These results may support the hypothesis that urinary excretion of PGE is determined mainly by urine flow rate in the situation of water diuresis.     

Familial aggregation of urinary kallikrein concentration in childhood: relation to blood pressure, race and urinary electrolytes

Biochemical alterations that have been correlated with elevated blood pressure have not received extensive epidemiologic study because of the technical difficulties involved. Because the excretion of urinary kallikrein is reduced significantly in adult hypertensives, we have studied urinary kallikrein in a cohort of children in whom familial aggregation of blood pressure has been demonstrated. Casual specimens of urine were obtained in household surveys, and urinary concentration of kallikrein was determined in 601 children aged 5-18 years. The children were from 163 families, whose members also had their blood pressures measured. Familial aggregation of urinary kallikrein concentration was found by analysis of variance (F=3.45, p less than 0.001) even in these casual specimens and was demonstrable for black and white children analyzed separately. Urinary kallikrein concentration was significantly lower in black children than in white children (p less than 0.001) and was positively correlated with urinary creatinine and urinary potassium and inversely related to urinary sodium concentrations. Urinary kallikrein concentration also was being altered by season (being lowest in the summer) and by time of day (being highest in the morning). Families with the lowest mean kallikrein concentrations tended to have higher blood pressures than did families with the highest mean kallikrein concentrations, although the effect is small and subject to many variables.     

Estimation of the flow of microbial nitrogen to the duodenum using urinary uric acid or allantoin

Data were collected from six experiments using duodenally cannulated Holstein dairy cows (88 combinations of cow and period) to evaluate the relationship between urinary purine metabolites and microbial N flow. Experiments evaluated the effects of dietary factors on microbial N production, which included 1) varying concentrations of ruminally degradable protein and nonstructural carbohydrates, 2) supplemental sources of protected amino acids, 3) grass silage treated with fibrolytic enzymes, 4) bacterial inoculation of corn silage, and 5) ruminal starch availability as affected by corn silages of varying maturity. The coefficient of determination for individual experiments that measured the relationship between microbial N flow and allantoin or uric acid excretion in urine ranged from 0.01 to 0.68 and 0.02 to 0.82, respectively. Across all experiments, the coefficients of determination between microbial N flow and allantoin or uric acid excretion in urine were r2 = 0.002 and 0.11, respectively. Removal of data from one experiment improved the overall coefficient of determination between microbial N flow and urinary uric acid to r2 = 0.32. Urinary allantoin excretion across experiments was negatively correlated with microbial N flow, but urinary allantoin excretion within experiments was positively correlated with microbial N flow. Uric acid excretion in urine was positively correlated with microbial N flow across and within experiments, except for one experiment. Our data demonstrate that uric acid excretion in urine can be used to predict microbial N production, except in early lactation, and that urinary allantoin excretion cannot be used to predict microbial N production accurately among cows at different stages of lactation.     

Replica cytology in cancer of the larynx: an evaluation of a replica method in the diagnosis of laryngeal malignancy

Dopamine, noradrenaline and adrenaline were measured in plasma and in urine, using double-isotope derivative techniques, in 46 normal subjects and in 17 tetraplegic patients with physiologically complete cervical spinal cord transections above the sympathetic outflow. Dopamine was present in plasma in normal subjects in a concentration of 0.33 mug/l +/- 0.06 (SEM). Twenty-four hour urinary excretion of dopamine averaged 248 mug +/- 22. There was a significant correlation between the 24 h urinary excretion of dopamine and of noradrenaline. In the normal subjects plasma dopamine and the urinary excretion of dopamine did not change during three days of fasting while urinary excretion of adrenaline increased twofold. In the normal subjects exercise significantly increased plasma dopamine from 0.25 mug/l to 0.43 mug/l, but significantly decreased the urinary excretion of dopamine. Exercise significantly increased the excretion of noradrenaline. In the tetraplegic patients the plasma dopamine concentration and the urinary excretion of dopamine were lower but not significantly different from the corresponding values in the normal subjects. Plasma noradrenaline and the urinary excretion of noradrenaline and adrenaline were significantly lower in the tetraplegic patients. It is concluded that dopamine is present in human plasma in concentrations similar to that of noradrenaline. Free dopamine in plasma and urine of normal subjects is not dependent on foot intake. Urinary dopamine may be derived from circulating dopamine. Urinary dopamine does not necessarily appear to reflect changes in plasma dopamine. The relationship between plasma dopamine and changes in adrenergic nervous activity deserves further investigation.     

Vagal dysfunction and impaired urinary sodium and water excretion in cirrhosis

OBJECTIVE: To evaluate the possible role of vagal impairment in the disturbances of urinary sodium and water excretion observed in cirrhosis. METHODS: Standard cardiovascular reflex tests were used to assess Autonomic function in 11 cirrhotic patients, and the response to an acute intravenous water load was determined. Changes in plasma noradrenaline, antidiuretic hormone, renin, and atrial natriuretic peptide also were evaluated. RESULTS: Patients with vagal dysfunction were shown to have significantly impaired urinary sodium and water excretion, compared with those whose cardiovascular tests were normal (5-h urinary sodium excretion, 32.3 +/- 9.0 vs. 69.4 +/- 12.7 mmol, p < 0.05; % water load excreted at 5 h, 67.8 +/- 10.5 vs. 109.2 +/- 3.67%, p < 0.008). This was associated with higher circulating noradrenaline, renin, and antidiuretic hormone levels after the water load in the vagal dysfunction group. Urinary sodium excretion correlated with the heart rate variation on deep breathing (r = 0.74, p < 0.013) and the heart rate response to atropine (r = 0.75, p < 0.020); the % water load excreted correlated with the number of abnormal cardiovascular tests in each patient (rS = 0.67, p < 0.02). Although patients with vagal abnormalities had worse liver function, urinary sodium and water excretion correlated better with parasympathetic tests than with standard parameters of hepatic function. CONCLUSIONS: The presence of vagal impairment in cirrhosis appears to be associated with impaired urinary sodium and water excretion, as well as disturbances in circulating vasoactive hormones. These findings could be due to an afferent defect resulting in diminished inhibitory input from intrathoracic volume and arterial baroreceptors, although a confounding effect of worse hepatic function in patients with vagal impairment cannot be excluded.     

Exposure to glycols and their renal effects in motor servicing workers

Ten car mechanics frequently exposed to glycol-based cooling liquids were followed during a workshift. Airborne ethylene and propylene glycol concentrations in the car mechanics' environment were measured. The car mechanics gave urine samples after the workshift and their excretion of ethylene glycol, propylene glycol, oxalic acid, calcium and ammonia was analysed and compared to that of unexposed office workers. Urinary succinate dehydrogenase activity and glycosaminoglycans were also measured in both groups. Airborne ethylene and propylene glycol concentrations in the car mechanics' environment were negligible. Urinary ethylene glycol excretion in exposed workers was significantly higher than that in unexposed workers, but propylene glycol excretion was at the same levels as in controls. In the exposed group, the excretion of the end metabolite of ethylene glycol, oxalic acid (47 +/- 11 mmol/mol creatinine, mean +/- SD, n = 10) differed slightly from that of controls (36 +/- 14 mmol/mol creatinine, mean +/- SD, n = 10). Urinary excretion of ammonia was higher among exposed workers than office workers. The excretion of calcium did not differ from that of controls. A marginally decreased urinary succinate dehydrogenase activity was found in the exposed men. The excretion of glycosaminoglycans was significantly lower in exposed workers. Therefore, it seems that ethylene glycol is absorbed by skin contact. The internal body burden is associated with oxaluria and increased ammoniagenesis typical of chronic acidosis.     

Opportunities for promoting palliative medicine in cancer research

OBJECTIVE: To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS: Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Renal clearances were calculated by dividing urinary excretions by the respective plasma concentrations. RESULTS: Before treatment, all patients had a normal plasma carnitine concentration. During treatment with cisplatin, the plasma total carnitine concentration increased by approximately 30% and normalized 7 days after stopping therapy. Urinary excretion of total carnitine increased by a factor of 10 during cisplatin administration and also normalized 7 days after cessation of chemotherapy. This increase was due to excretion of both free carnitine and acylcarnitine and averaged approximately 1 mmol carnitine per day. Similarly, urinary clearance of total carnitine was increased during therapy with cisplatin by a factor of approximately 8 and returned to normal 7 days after chemotherapy. In comparison, patients with similar malignancies treated with radiotherapy showed no significant increase in renal carnitine excretion. Similar to urinary excretion of carnitine, excretion of glucose and phosphate, two metabolites also reabsorbed by the proximal tubule of the nephron, was increased during therapy with cisplatin. There was a strong linear correlation between urinary excretion of free carnitine and acylcarnitines. CONCLUSIONS: Treatment with cisplatin is associated with a tenfold increase in renal carnitine excretion, most likely due to inhibition of carnitine reabsorption by the proximal tubule of the nephron. Well-nourished patients support this loss of carnitine even after repeated cycles of chemotherapy without developing hypocarnitinaemia. However, cachectic patients with decreased dietary carnitine uptake may develop carnitine deficiency when treated repeatedly with chemotherapies including cisplatin.     

Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotriene production

Asthma may respond to dietary modification, thereby reducing the need for pharmacologic agents. This study determined the effectiveness of n-3 polyunsaturated fatty acid (PUFA) ingestion in ameliorating methacholine-induced respiratory distress in an asthmatic population. The ability of urinary leukotriene excretion to predict efficacy of n-3 PUFA ingestion was assessed. After n-3 PUFAs in ratios to n-6 PUFAs of 0.1:1 and 0.5:1 were ingested sequentially for 1 mo each; patient respiratory indexes were assessed after each treatment. Forced vital capacity (FVC), forced expiratory volume for 1 s (FEV1), peak expiratory flow (PEF), and forced expiratory flow 25-75% (FEF 25-75) were measured along with weekly 24-h urinary leukotriene concentrations. With low n-3 PUFA ingestion, methacholine-induced respiratory distress increased. With high n-3 PUFA ingestion, alterations in urinary 5-series leukotriene excretion predicted treatment efficacy. Elevated n-3 PUFA ingestion resulted in a positive methacholine bronchoprovocation dose change in > 40% of the test subjects (responders). The provocative dose to cause a 20% reduction (PD20) in FEV1, FVC, PEF, and FEF25-75 values could not be calculated because of a lack of significant respiratory reduction. Conversely, elevated n-3 PUFA ingestion caused some of the patients (nonresponders) to further lose respiratory capacity. Five-series leukotriene excretion with high n-3 PUFA ingestion was significantly greater for responders than for nonresponders. A urinary ratio of 4-series to 5-series leukotrienes < 1, induced by n-3 PUFA ingestion, may predict respiratory benefit.     

Religiosity as a protective or prognostic factor of depression in later life; results from a community survey in The Netherlands

OBJECTIVES: This study explored the possibility of using urinary 1-naphthol excretion as a marker of complex exposure among workers handling creosote. METHODS: Urine specimens of 6 workers from a creosote impregnation plant, where railroad ties were impreganted with coal tar creosote, were collected during 1 workweek, and the concentration of 1-naphthol was determined. 1-Naphthol in spot urine samples of 5 occupationally nonexposed male smokers was used as the background reference. Concurrently, naphthalene and 10 different polycyclic aromatic hydrocarbons (PAH) were determined in personal air samples. RESULTS: The mean airborne exposure of the workers was 1.5 mg/m3 for vaporous naphthalene, 5.9 micrograms/m3 for particulate PAH and 1.4 micrograms/m3 for PAH with 4-6 aromatic rings. The mean urinary concentration of 1-naphthol at the end of the workshift was 20.5 (range 3.5-62.1) mumol/l, whereas the referents' urinary concentration was below the detection limit (0.07 mumol/l). Airborne naphthalene correlated fairly well with 1-naphthol when measured at the end of the shift (r = 0.745). CONCLUSIONS: This method of analysis for 1-naphthol is sufficiently sensitive for measuring low occupational exposures to naphthalene. Low background exposures are, however, unlikely to result in detectable urinary levels of 1-naphthol. Since naphthalene is the most abundant compound in creosote vapor, urinary 1-naphthol determination serves well as a biological marker of exposure to vaporous creosote. Urinary 1-naphthol alone is not, however, a suitable marker for inhalatory or cutaneous exposure to PAH originating from creosote.     

Endoscopic endonasal dacryocystorhinostomy: indications, technique and results

To understand the changes of urinary endothelin-1 (ET-1) concentrations in acute renal failure (ARF) and to investigate the origin of human urinary ET-1, we studied urinary ET-1 excretion in 70 normal children and 12 children with ARF caused by tubular dysfunction. Urinary ET-1 excretion was expressed as a ratio of urinary ET-1 to urinary creatinine (ET-1/Cr). Among healthy children, the highest urinary ET-1/Cr values were found during infancy. In patients with ARF, there was a positive correlation between urinary ET-1/Cr values and daily total urinary ET-1 (r = 0.42, n = 26, p < 0.05). Plasma ET-1 concentrations were elevated in children with ARF during the period of peak serum creatinine concentration. During the course of ARF, the lowest urinary ET-1/Cr value occurred during the period of peak serum creatinine, whereas the plasma ET-1 concentration declined after the peak. These results provide insight into the developmental changes of urinary ET-1 values in normal children, and illustrate the pattern of changes in plasma and urinary ET-1 concentrations during the course of ARF in children. The results suggest that renal production, rather than clearance from the circulation by glomerular filtration, may be the source of urinary ET-1.     

Evaluation of the FREEDOM O2, DC Concentrator, a portable oxygen concentrator capable of operating under car battery power

Many sensitive biomarkers are available for the surveillance of the early health effects of chemicals on humans. This study was conducted to evaluate the usefulness of glycosaminoglycans (GAG) as biomarkers of early kidney effects in exposure to 2-alkoxyethanols and their acetates. GAG were compared with effects on the urinary beta-N-acetylglycosaminidase activity (NAG). According to the results of the present study, the excretion rate of GAG was higher among women than men. On the other hand, the excretion rate of GAG was lower among exposed subjects than among the controls, and the level was decreased at the tested levels of exposure. The NAG activity was higher in most of the exposed groups than in the controls. The data indicated that an appropriate urinary limit value for ethoxyacetic acid was 30 mmol/mol creatinine in postshift samples and that this value corresponded to an 8-hour exposure level of 2 cm3/m3 2-ethoxyethylacetate. Urinary butoxyacetic acid excretion of 60 mmol/mol creatinine corresponded to the inhalation exposure level of 5 cm3/m3 2-butoxyethanol and its acetate in postshift samples.     

Trihalomethane and Haloacetic Acid Disinfection By-Products in Full-Scale Drinking Water Systems

Trihalomethane (THM), haloacetic acid (HAA5), and total organic carbon (TOC) data provided by the Missouri Dept. of Natural Resources for drinking water treatment systems in the State of Missouri was analyzed for the years 1997–2001. These data indicated that a significant portion of systems exceeded the current regulatory limits of 80 and 60?μg/L for THM and HAA5 in these years. The vast majority of the treatment plants exceeding the regulatory limits were small plants with service populations less than 10,000 people. No significant temporal trend in either THM or HAA5 was noted for the years 1997–2001. This work suggests that the proposed use of a locational running annual average may have a significant effect on compliance. The use of chloramines (combined chlorine) versus free chlorine (HOCl/OCl?) as a residual disinfectant was shown to significantly reduce both THM and HAA5 in systems that treat their own water (primary systems), but did not have a significant effect in systems which purchase their water from primary systems (secondary systems). Comparison of finished water at the treatment plant versus in the distribution system suggested that a majority of THM and HAA5 may be produced within the plant as opposed to the distribution system. Hence, reducing these chlorinated disinfection byproducts within the treatment plant itself should be a key focus for achieving compliance, and supports Environmental Protection Agency disinfection byproducts compliance guidelines using enhanced coagulation.     

Renal water channel expression in newborns: measurement of urinary excretion of aquaporin-2

Aquaporin-2 (AQP-2) encodes the vasopressin-regulated "water channels" of the renal collecting duct and is excreted in human urine. We measured urinary excretion of AQP-2 by radioimmunoassay in 15 term and 10 preterm infants on day 1 and day 4 of life to determine the molecular basis of water balance during the newborn period. AQP-2 was detectable in the urine of term and preterm newborns, but AQP-2 excretion was severalfold less than the reported level in normal adults. Urinary excretion of AQP-2 significantly decreased postnatally, in parallel with a reduction in urine osmolality and arginine vasopressin (AVP) excretion. Urinary AQP-2 correlated positively and significantly with urine osmolality on days 1 and 4 and with AVP on day 1 in both groups. No significant differences were detected in AQP-2 levels between term and preterm newborns. Our findings suggest that vasopressin-regulated water channels are expressed in the renal collecting duct of both term and preterm newborns, although to a lesser extent as compared with adults, and these channels encoded by AQP-2 contribute to the urine concentrating power of the newborn kidney.     

Hyperoxaluriaas a complication of intestinal diseases (author's transl)

Urinary oxalate excretion was measured in healthy persons and patients with Crohn's disease, colitis ulcerosa, sprue and other diseases accompanied with malabsorption, and patients with insufficiency of the exocrine pancreas gland. Further measurements were made in patients after resection of parts of the small intestine or the colon. We found a clear increase of urinary oxalate excretion in patients with resected parts of the small intestine, sprue or other malabsorption syndromes. In 4 patients with resected parts of small intestine or pancreas we even found urolithiasis. Urinary oxalate excretion correlated significantly with steatorrhoea and increased if larger parts of small intestine were resected. Increased resorption of oxalate from food causes increased urinary excretion. Details about the patho-mechanism of this increased excretion are not known yet; an important factor seems to be the reduced absorption of fat in the small intestine.     

Urinary excretion of apo(a) fragments in NIDDM patients

Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA1c or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM.     

Hypomethylation in cervical tissue: is there a correlation with folate status?

5-Aminolevulinic acid (ALA) is the first intermediate substrate in the heme synthetic pathway and is the substrate of aminolevulinic acid dehydratase (ALAD, porphobilinogen synthase). Because lead effectively inhibits ALAD activity, resulting in accumulation of ALA in urine and blood, urinary ALA (ALAU) has been used as a biomarker for lead exposure or early biologic effect of lead. Intraindividual variation in urinary excretion of ALA requires the use of 24-hour urine samples or adjustment of single urine samples by other normalizing variables, such as urinary creatinine concentration. Previous studies of ALAU concentration have used various adjustment methods; however, few have compared creatinine-adjusted ALAU concentration with ALA concentration in plasma (ALAP) from subjects with low (< 30 micrograms/dL) to moderate (< 60 micrograms/dL) levels of blood lead. To determine if creatinine-adjusted ALAU is associated with ALAP, we measured ALAU, ALAP, and urinary creatinine in 65 Korean lead workers with blood lead concentrations in the range of 14-60 micrograms/dL. ALAU, ALAU/creatinine, or ALAU/log creatinine all correlated with ALAP. However, ALAU/creatinine correlated more closely with ALAP based on Spearman's r (rs = 0.40, P, = 0.0009), supporting the use of ALA/creatinine in single urine samples as a surrogate for ALAP.     

Association between the clastogenic effect in peripheral lymphocytes and human exposure to arsenic through drinking water

We describe the association between structural chromosome aberrations (CAs) and parameters of exposure to arsenic among 42 individuals exposed to arsenic through well waters in Finland. The median concentration of arsenic in the wells was 410 microg/l, the total arsenic concentrations in urine (As-tot) was 180 microg/l, and in hair 1.3 microg/g, for current users (n = 32) of contaminated wells. Urinary arsenic species and CAs were also analyzed in eight control individuals from the same village who consumed water which contained arsenic <1.0 microg/l (detection limit). Increased arsenic exposure, indicated best by increased concentrations of arsenic species (inorganic arsenic, methylarsonic acid (MMA), dimethylarsinic acid (DMA)) in urine, was associated with increased frequency of CAs. The increased urinary ratio of MMA/As-tot and the decreased ratio of DMA/As-tot were associated with increased CAs when all aberration types, including gaps, were considered. Associations between CAs and arsenic exposure indicators were stronger among current users than among persons who had stopped using the contaminated well water for 2-4 months before sampling (ex-users, n = 10). Furthermore, there was a positive but not statistically significant association between CAs and arsenic in hair among the current users, but not among the ex-users, who still had relatively high arsenic concentrations in hair. The results suggest that the effect observed in the present study reflects relatively recent arsenic exposure.     

Sodium excretion in children with lithogenic disorders

INTRODUCTION: The causes of nephrolithisis are multifactorial and have not yet been enough investigated [1]. Hypercalciuria is the most common cause of metabolic nephrolithiasis [2-4]. Close relationship between urinary calcium and urinary sodium has been a subject of reported observations in the past, showing that high urinary sodium is associated with high urinary calcium [5-7]. Hyperoxaluria, hyperuricosuria and cystinuria are also metabolic disorders that can lead to nephrolithiasis. Recent studies have indicated that urinary elimination of cystine is influenced by urinary sodium excretion. Based on these observations it has been hypothesised that patients with high urinary sodium excretion are at high risk of urinary stone disease. The purpose of the study was to investigate sodium excretion in a 24-hour urine and first morning urine collected from children with lithogenic metabolic abnormalities (hypercalciuria, hyperoxaluria, hyperuricosuria, cystinuria), both with nephrolithiasis and without it, in order to determine its significance in urinary calculi formation. PATIENTS AND METHODS: Urinary sodium excretion was investigated in 2 groups of children: patients with lithogenic metabolic abnormalities, but without urinary stone disease (L group) and patients with nephrolithiasis (C group). Both groups were divided into 2 subgroups: patients with hypercalciuria and without it. There were 22 patients in group L (mean age 11.97 +/- 4.13 years), of whom 17 formed a hypercalciuric subgroup and 5 formed a non-hypercalciuric subgroup (3 patients with hyperuricosuria and 2 patients with hyperoxaluria). Group C consisted of 21 patients with nephrolithiasis (mean age 12.67 +/- 3.44 years), of whom 6 formed a hypercalciuric subgroup and 15 formed a non-hypercalciuric group (2 patients with cystinuria and 13 patients without lithogenic metabolic abnormalities). Control group consisted of 42 healthy age-matched children. All subjects had a normal renal function. A detailed history and clinical examination were done, and ultrasonography was performed in all patients. A 24-hour urine, first morning urine and serum specimen were analysed for sodium, potassium, calcium, uric acid, urea and creatinine. Fractional excretion of sodium, as well as urinary sodium to creatinin ratio and urinary sodium to potassium ratio, were calculated from the findings. Sodium and potassium levels were determined by flame photometry, calcium was measured by atomic absorption technique (Beckman Atomic Spectrophotometer, Synchron CX-5 model, USA), uric acid by carbonate method and creatinine by Jaffe technique. Cystine and dibasic amino acids were quantified by ion chromatography. Urinary oxalate excretion was determined by enzyme spectrophotometry. Hypercalciuria was defined by 24-hour calcium excretion greater than 3.5 mg/kg per day and/or calcium to creatinine ratio greater than 0.20 [8]. Uric acid excretion was expressed as uric acid excretion factored for glomerular filtration, according to Stapleton's and Nash's formula [9]. Normal values were lower than 0.57 mg/dl of glomerular filtration rate in 24-hour samples. Mean values were statistically analyzed by Pearson's linear correlation and analysis of variance (ANOVA). RESULTS: Urinary sodium concentration values including urinary sodium to potassium ratios, are shown in Table 1. We found that urinary sodium excretion was significantly increased in patients of both L and C groups when compared with controls (p < 0.05). Further analysis of the subgroups showed that urinary sodium excretion was significantly higher only in patients with hypercalciuria of both L and C groups in comparison to controls (p < 0.05) (Table 2). A significant positive correlation was found between 24-hour urinary sodium to creatinine ratio and urinary calcium to creatinine ratio (r = 0.31; p < 0.001) (Graph 1), as well as between urinary sodium to potassium ratio in 24-hour and first morning urine (r = 0.69; p < 0.001) (Graph 2). (A