Mean Excretion Research Articles

Continuous veno-venous hemofiltration with dialysis removes cytokines from the circulation of septic patients

To determine whether continuous veno-venous hemofiltration with dialysis leads to extraction of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and removal rates of these cytokines and their effect on serum cytokine concentrations. Prospective, controlled study of TNF-alpha IL-1 beta extraction by continuous veno-venous hemofiltration with dialysis in patients with septic acute renal failure. Intensive care unit of a tertiary institution. Eighteen critically ill patients with sepsis and acute renal failure. Control group of six patients experiencing an acute illness while undergoing chronic hemodialysis. Collection of blood samples before continuous veno-venous hemofiltration with hemodialysis. Simultaneous collection of prefilter blood and ultradiafiltrate after 4 and 24 hrs of treatment. TNF-alpha and IL-1 beta concentrations were measured in blood and ultradiafiltrate. Their clearances and daily extraction were calculated and compared with a control group. TNF-alpha was detected in 66.6% of serum samples of patients with septic acute renal failure; IL-1 beta was detected in 55% of patients' sera samples. Both TNF-alpha and IL-1 beta were cleared by the hemofilter during continuous veno-venous hemofiltration with dialysis. The mean clearance for TNF-alpha was 30.7 L/day (95% confidence interval 22.4 to 39) with a daily mean excretion of 14.1 micrograms (95% confidence interval 1.7 to 26.5). Mean IL-1 beta clearance was 36.1 L/day (95% confidence interval 25.4 to 46.8) equivalent to a mean daily IL-1 beta excretion of 1 microgram (95% confidence interval 0.9 to 1.1). No measurable concentrations of TNF-alpha or IL-1 beta were found in the serum or ultrafiltrate specimens of control patients. These findings demonstrate that continuous veno-venous hemofiltration with dialysis can remove both TNF-alpha and IL-1 beta from the circulation of septic, critically ill patients. This cytokine extraction may prove to be of benefit in attenuating the progression of multiple organ dysfunction in patients with sepsis-associated renal failure, who are receiving continuous veno-venous hemofiltration with dialysis. This potential benefit of existing hemofiltration therapies supports their preferential implementation in patients with renal failure associated with severe sepsis. These observations may stimulate the modification of filtration membrane design seeking to specifically augment the clearance from the circulation of a variety of such cytokines.

GENETIC VARIATION AND COVARIATION FOR CHARACTERISTICS ASSOCIATED WITH CADMIUM TOLERANCE IN NATURAL POPULATIONS OF THE SPRINGTAIL ORCHESELLA CINCTA (L.).

Heavy metals can be strong and stable directional selective agents for metal-exposed populations. Genetic variation for the metal-tolerance characteristic "cadmium excretion efficiency" was studied in populations of the collembolan Orchesella cincta from a reference- and a metal-contaminated forest soil. Previously it has been shown that "excretion efficiency" influences tolerance through midgut-mediated immobilization and excretion of toxic metal ions, and that an increased mean excretion efficiency is present in animals inhabiting metal-contaminated litter. In the present research, offspring-parent regressions showed that additive genetic variation for cadmium excretion efficiency was present in the population from the reference site. The heritability estimate was 0.33. In the natural population exposed to heavy metals from an industrial source, additive genetic variation was not significantly different from zero. Differences in the heritability between the reference and the exposed population were not significant. Genetic variation for cadmium excretion efficiency allows for a response to selection in the reference population. Such a response has probably occurred in the metal-exposed population. Half-sib analysis with animals from the reference population was used to estimate genetic variation and maternal effects for excretion efficiency, relative growth rate and molting frequency, and to determine genetic correlations between these characteristics. Additive genetic variation was demonstrated for all three characteristics, heritability estimates were 0.48, 0.75 and 0.46, respectively. Maternal effects were low for excretion efficiency and molting frequency, but may be present for relative growth rate. Phenotypic and genetic correlations among these characteristics were positive. The environmental correlation between relative growth rate and molting frequency was positive, others were negative. Direct selection for any of the characteristics, or genetic correlations between tolerance characteristics and growth characteristics, or both may have caused the responses previously observed in field populations.

Kinetics of amatoxins in human poisoning: therapeutic implications.

The kinetics of alpha and beta amanitin were studied in 45 patients intoxicated with Amanita Phalloides. The amatoxins were analyzed by high performance liquid chromatography in plasma (43 cases), urine (35 cases), gastroduodenal fluid (12 cases), feces (12 cases) and tissues (4 cases). All patients had gastrointestinal symptoms and 43 developed an acute hepatitis. Two patients underwent successful liver transplantation. Eight patients, of whom three were children, died. The detection of amatoxins in the biological fluids was time dependent. The first sample was obtained at an average of 37.9 h post ingestion in the patients with positive results and at 70.6 h in the samples without detectable amatoxins. Plasma amatoxins were detected in 11 cases at 8 to 190 ng/mL for alpha and between 23.5 to 162 ng/mL for beta. In 23 cases amatoxins were detected in urine with a mean excretion per hour of 32.18 micrograms for alpha and 80.15 micrograms for beta. In 10 patients the total amounts eliminated in the feces (time variable) ranged between 8.4 and 152 micrograms for alpha amanitin and between 4.2 and 6270 micrograms for beta amanitin. In three of four cases amatoxins were still present in the liver and the kidney after day 5. Amatoxins were usually detectable in plasma before 36 h but were present in the urine until day 4. The rapid clearance indicates that enhanced elimination of amatoxins requires early treatment. Clearance of circulating amatoxins by day 4 spares the transplanted liver.

Erythrocyte sodium-lithium countertransport activity and total body insulin-mediated glucose disposal in normoalbuminuric normotensive Type 1 (insulin-dependent) diabetic patients

Insulin resistance in Type 1 (insulin-dependent) diabetes mellitus may be associated with raised erythrocyte sodium-lithium countertransport activity in patients with hypertension, or nephropathy, or both. However, in these circumstances it is difficult to separate the impact of hypertension, hyperlipidaemia and nephropathy on erythrocyte sodium-lithium countertransport from that of insulin resistance. We have therefore examined the relationship between insulin-mediated glucose disposal and erythrocyte sodium-lithium countertransport in 41 normotensive (mean blood pressure 120/74 mmHg), normoalbuminuric (mean albumin excretion 6.2 micrograms/min), normolipidaemic (mean serum cholesterol 4.3 mmol/l and mean serum triglycerides 1.0 mmol/l) Type 1 diabetic patients. Erythrocyte sodium-lithium countertransport was on average 0.31 mmol Li.h-1.l erythrocytes-1 (range 0.07-0.69). Nine patients had values above 0.40 mmol Li.h-1.l erythrocytes-1 (0.51 +/- 0.10 mmol Li.h-1.l erythrocytes-1). The patients with high erythrocyte sodium-lithium countertransport were matched for age, sex, BMI, HbA1 and duration of diabetes, with nine patients with normal erythrocyte sodium-lithium countertransport. Insulin-mediated glucose disposal was evaluated during the last hour of a euglycaemic clamp (insulin 0.015 U.kg-1.h-1; blood glucose clamped at 7.0 mmol/l). The free insulin levels were comparable between the patients with high and normal erythrocyte sodium-lithium countertransport (37.2 +/- 14.7 mU/l and 34.7 +/- 17.2 mU/l respectively). Insulin-mediated glucose disposal was on average 3.1 +/- 1.5 (range 0.8-6.8) mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of nefiracetam and three metabolites in humans and stereoselective hydroxylation of its pyrrolidine ring.

1. The kinetics of nefiracetam (I) and three metabolites (II-IV) were investigated in healthy volunteers. Compounds I-IV in serum and urine were measured by h.p.l.c. 2. After a single 200 mg dose of nefiracetam the drug was absorbed rapidly and showed peak serum levels of 16.3 +/- 0.9 nmol/ml. Cmax values of the three metabolites were comparatively low (0.96-4.89 nmol/ml), and tmax and t1/2 values of the metabolites (4.1-9.6 h and 7.8-21.9 h, respectively) were longer than those of I (1.6 h and 3.9 h respectively). Urinary excretion of I in 24 h was about 5% of the dose. The major urinary metabolite, a pyrrolidine ring scission product (IV), had a mean total excretion of 17.8% dose. The total of all four compounds in urine amounted to 43.4% dose. 3. In a multiple-dose study (daily 3 x 200 mg doses of nefiracetam for 7 days), the serum concentration profile of each compound indicated that the steady state was reached in 7 days. 4. Metabolite II existed as a racemate and III mainly as the (-)-enantiomer in human urine.

Metabolism of piperidine-type phenothiazine antipsychotic agents. IV. Thioridazine in dog, man and rat.

1. The metabolism of thioridazine was studied in adult male volunteers, female rat and female dog after oral administration of 50 mg, 20 mg/kg and 100 mg over 30 h, respectively. 2. Metabolites in organic extracts of the urine obtained from each species were analysed by plasmaspray h.p.l.c.-mass spectrometry. For phenolic metabolites the crude extracts from each species were derivatized with a silylating reagent (with and without prior enzymic hydrolysis) prior to h.p.l.c.-mass spectrometric analysis. The structures of metabolites, with the exception of phenols, were confirmed by comparison of their chromatographic behaviours and mass spectral data with those of authentic standards. 3. The metabolites identified in the urine of all three species were mesoridazine, sulforidazine, thioridazine ring sulphoxide, mesoridazine ring sulphoxide, sulforidazine ring sulphoxide, the lactam of mesoridazine ring sulphoxide and unconjugated phenolic derivatives of mesoridazine and sulforidazine. Other compounds observed were: unchanged thioridazine (dog, rat), sulforidazine N-oxide (man), N-desmethylthioridazine ring sulphoxide (dog, rat), N-desmethylmesoridazine ring sulphoxide (dog, rat), the lactam of sulforidazine ring sulphoxide (rat, man), phenolic derivative of thioridazine in unconjugated form (rat), and conjugated form (man), and conjugated phenolic derivative of mesoridazine (man). 4. Thioridazine and six of its metabolites present in the urine of man, rat and dog were quantified by a h.p.l.c.-UV procedure. The mean total urinary excretion (+/- SD) of the measured analytes in man, rat and dog were determined to be 4.3 +/- 2.9, 4.8 +/- 1.7 and 12.1 +/- 5.4% of the dose, respectively. The mean excretion of the lactam of mesoridazine ring sulphoxide was greater in man (1.2 +/- 1.0%) and rat (0.2 +/- 0.2%) than dog (< 0.02%). Moreover, the mean excretion of the lactam of sulforidazine ring sulphoxide was quantifiable in both man (0.5 +/- 0.4%) and rat (0.2 +/- 0.2%). 5. Interspecies comparison of the lactam metabolites indicated that both qualitatively and quantitatively, man more closely resembled rat than dog. Similar observations were previously reported for mesoridazine and sulforidazine, therefore rat may be a more suitable animal than dog to undertake further study of the importance of C-oxidation of the piperidine ring of this class of drug.

Metabolic Fate of Eptastigmine, a New Competitive Inhibitor of Acetylcholinesterase. (I). Absorption, Distribution and Excretion of 3H-Eptastigmine after Single Oral Administration in Rats.

Eptastigmine, ((3aS, 8aR)-1, 2, 3, 3a, 8, 8a-hexahydro-1, 3a, 8-trimethylpyrrolo [2, 3-b] indol-5-ol-heptylcarbamate L-tartrate), is a competitive inhibitor of acetylcholinesterase. Absorption, distribution and excretion of radioactivity were investigated in rats (n=3) after single oral or intravenous administration of 3H-eptastigmine. 1. After oral administration of doses ranging from 2 to 8mg/kg, blood levels of radioactivity increased proportionally to administered dose with peak blood concentration occurring at about one hour and declined with half-lives (t1/2β) of 13-16hr. Based on the AUC values obtained after intravenous and oral administration, oral absorption ratio of 3H-eptastigmine was estimated to be 70-100%. 2. After oral dosin g, the radioactivity was rapidly and widely distributed to tissues and maintained in high concentrations in the liver and gastrointestinal tract. Radioactivity in most of tissues declined slower than that in the plasma. At 24hr, the level in each tissue decreased to about 10% of the corresponding maximum level. There was no evidence of accumulation of 3H in any tissue. 3. Mean excretion of radioactivity was 60.5 and 18.1% of the dose in the urine and feces, respectively, within 24hr after intravenous dosing. In case of oral dosing, the mean excretion of radioactivity in urine and feces were 40.2-51.3 and 29.0-33.5% of the dose, respectively. 4. Mean plasma levels of unchanged eptastigmine reached the maximum concentration at 0.5hr after oral dosing, and then declined with half-life of 1.1hr. The AUC value for unchanged eptastigmine accounted only for 0.4% of that for the total radioactivity. 5. Marked inhibition of RBC acetylcholinesterase activity was o bserved after administration of the 8mg/kg. At 1hr after dosing, the mean value of acetylcholinesterase activity decreased to 15% of the pre-dosing level and remained suppressed for up to 8hr after dosing. 6. Based on the results from the blood profile of radioactivity and time course of acetylcholinesterase inhibition, we concluded that at least one active metabolite exists in the blood.

Chronic occupational exposure to organic solvents. XV. Glycol ether exposure during the manufacture of brakehoses.

Twenty-two persons (20 men and 2 women) were examined for their external and internal exposure to the glycol ether 1-methoxypropan-2-ol (PGME) during the production, leak testing and mounting of brakehoses. For the measurement of external exposure, personal air monitoring was the method of choice. Average concentrations of PGME of 82.2 mg/m3 (22.3 ppm), 68.6 mg/m3 (18.6 ppm) and 11.3 mg/m3 (3.1 ppm) were found in the air of the brakehose production, leak test and mounting areas, respectively. For the estimation of internal exposure to PGME, this glycol ether was measured in both urine and blood. The biological samples were taken post-shift. The highest internal exposure levels were found in the brakehose production section and in the leak test area. The average post-shift concentrations for PGME in workers in the brakehose production section were 4.6 mg/l in urine and 13.5 mg/l in blood; the corresponding figures for workers in the leak test area were 4.2 mg/l in urine and 11.0 mg/l in blood. In blood and urine samples of workers engaged in the mounting area, PGME levels were below the detection limits. The elimination kinetics of PGME were also studied in three highly exposed persons, and mean excretion half-lives of PGME of approximately 4.4 h were found. On the basis of our results we made a rough calculation of a future biological tolerance value: we would except that concentrations of 38-109 mg per litre of blood and 10-31 mg per litre of urine would correspond to the German MAK value for PGME (375 mg/m3).

A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets.

Current treatment of X-linked hypophosphatemia (XLH) employs the combined administration of oral phosphate and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Although this drug regimen significantly improves the clinical course of the disease in children, the value of medical treatment in symptomatic adults with XLH has not been established. We, therefore, investigated the clinical, biochemical, and histological responses to phosphate and 1,25-(OH)2D3 in 16 symptomatic adult patients with XLH followed for a mean of 4.2 yr. Eighty-seven percent of the patients had an improvement in bone or joint pain with therapy. There was a significant increase in mean serum phosphate (from 0.61 +/- 0.03 to 0.77 +/- 0.03 mmol/L) and urinary calcium excretion (from 2.45 +/- 0.38 to 4.39 +/- 0.44 mmol/day) with treatment. Pretreatment bone biopsies demonstrated findings characteristic of osteomalacia, including abnormally increased osteoid volume and decreased mineral apposition rates. Treatment was accompanied by a significant decrease in osteoid thickness as well as a reduction in mean osteoid volume. However, therapy did not completely normalize these parameters. Disease severity, as assessed by histomorphometric parameters, did not correlate with any pretreatment serum or urinary biochemical measurement, but did seem to correlate with symptom score. Although most patients tolerated therapy without difficulty, 1 patient developed tertiary hyperparathyroidism during treatment and renal insufficiency that progressed despite cessation of therapy. This study provides evidence that therapy with oral phosphate and 1,25-(OH)2D3 in symptomatic adults with XLH can result in significant clinical and histomorphometric improvement.

Urinary excretion of angiotensin I, II, arginine vasopressin and oxytocin in patients with anaphylactoid reactions.

Human urine samples, purified on octadecasilyl-silica cartridges, contained immunoreactive angiotensin I, II, arginine vasopressin and oxytocin. The daily excretion of these peptides in healthy volunteers was 190.00 +/- 38.43 (n = 12), 17.48 +/- 3.09 (n = 12), 63.43 +/- 14.84 (n = 8) and 13.52 +/- 1.42 (n = 7) pmol/24 hr, respectively (mean +/- s.e.m.). Patients with a history of anaphylactoid reactions to drugs or food additives showed clinical symptoms such as urticaria, flush, nausea, dizziness and hypotension after oral provocation with cyanocobalamine, propyphenazone, acetylsalicylic acid and sodium benzoate. In five of the seven patients, angiotensin I and II were increased several fold in the urine fractions after symptoms were reported. The average increase in the urine concentration of both peptides was fourfold and 5.5-fold. In three out of five patients, the mean excretion of arginine vasopressin and oxytocin immunoreactive material was also elevated by a factor of 5.7 and 4.4, respectively. Oral provocation with a placebo failed to elicit anaphylactoid symptoms or an increase in the urine levels of angiotensin I or angiotensin II. Angiotensin I and angiotensin II-like immunoreactivity could be characterized on HPLC as Ile5-angiotensin I, Ile5-angiotensin II and angiotensin II metabolites. HPLC characterization of immunoreactive arginine vasopressin and oxytocin in two different gradient systems showed retention times different than the retention times of the corresponding synthetic standard peptides indicating that both peptides are not authentic AVP and OXT. These results suggest that angiotensin I and angiotensin II may be involved in the clinical events observed during some forms of anaphylactoid reactions.

Effectiveness of entertic coated pancreatic enzymes given before meals in reducing steatorrhea in children with cystic fibrosis

In vitro data indicate that length of enzyme incubation with food critically affects enzyme dissolution and presumably effectiveness. This study compared the effectiveness of enteric coated (EC) pancreatic enzymes given before meals with those given during meals (15 minutes after beginning of meal) in reducing steatorrhea in well-nourished children with cystic fibrosis. Eight children (6 years 11 months old to 14 years 7 months old) were studied in the General Clinical Research Center at Indiana University Hospital, Indianapolis. A crossover study design randomly assigned enzymes before or during meals during two consecutive 7-day treatment periods for each child. No difference in fat excretion was documented for the total group when the children who took enzymes before meals were compared with those who took enzymes during meals. However, a stepwise multiple regression analysis of the difference (before minus during) in fat excretion on sex, age, enzyme number, and treatment order documented a positive correlation of age with fat excretion (r = .83). Mean fat excretion in younger children (less than 10 years old) decreased significantly when enzymes were given before meals (7.14 +/- 1.95%) rather than during meals (9.92 +/- 1.61%) (P = .004). The difference in fat excretion (mean = 2.78 +/- 0.55%, range = 1.4% to 4%) translates into a half to one full year's growth potential. Younger children with cystic fibrosis may benefit clinically from taking EC enzymes before meals.

Liquid chromatographic determination of hyoscine (scopolamine) in urine using solid phase extraction.

A sensitive method for the determination of hyoscine (scopolamine) in urine is described. After concentration and "clean-up" on C18 and CN solid phase extraction columns, hyoscine was quantified by high performance liquid chromatography with coulometric detection (oxidation at +0.9 V). The limit of detection was 5 ng per sample and the precision for 5 mL samples containing 2 ng/mL was 12.3%. The method was applied to urine samples collected from 12 volunteers wearing Scopoderm TTS patches. The mean excretion rate of unmetabolized hyoscine was 0.45 micrograms/h and 87% of the total hyoscine was present as conjugates. Apohyoscine (aposcopolamine) was identified as a urinary metabolite. The significance of this with regard to hyoscine assays is discussed.

Metabolic Studies in Kidney Stone Disease

Patients with kidney stones (n = 59) and healthy controls (n = 31) collected a 24-hour urine sample and later underwent a 6-hour 'fast and load' test in which an oral calcium load was taken after 2 hours. In the 24-hour urine sample, mean calcium excretion was higher in patients than controls, while mean urate, oxalate and citrate levels were similar. The patients had higher levels of fasting plasma calcium, serum calcitriol and fasting urinary calcium, and lower levels of plasma phosphate than did the controls. Following the calcium load, plasma and urinary calcium increased similarly in both groups. Serum parathyroid hormone (PTH) levels were similar in both groups and decreased similarly following the calcium load. Multiple linear regression, relating the presence or absence of stone formation to all variables, found the only variables significantly related to stone formation to be plasma levels of calcium (p less than 0.001) and phosphate (p = 0.001) and fasting urinary urea (p less than 0.001), and 24-hour urinary calcium excretion (p less than 0.05). Urinary oxalate and citrate were not related to stone formation. The data do not support the hypothesis that primary stimulation by calcitriol produces a normal fasting plasma calcium level, with an exaggerated increase after an oral calcium load. The findings instead suggest an abnormality of parathyroid cell 'set point', such that PTH secretion continues until the plasma calcium level is a little higher and the phosphate a little lower than in controls.

Population based data on urinary excretion of calcium, magnesium, oxalate, phosphate and uric acid in children from Cimitile (southern Italy).

Population based data on 24-h urinary excretion of calcium, oxalate, magnesium, phosphate, uric acid and creatinine were collected from 220 children (aged 3-16 years) living in Cimitile, Campania, southern Italy. Mean excretion rates for 7 days were correlated with age, body weight, body mass index and height. The prevalence of hypercalciuria (greater than 4 mg/kg body weight) and of hyperoxaluria (greater than 60 mg/day) were 9.1% and 1.8%, respectively. The same 20 children were also identified as hypercalciuric when a calcium/creatinine ratio of greater than 0.15 was considered. No significant differences between boys and girls were found in the urinary excretion of the five constituents implicated in urolithiasis. The study data provide additional childhood reference values for urinary excretion of compounds related to stone formation.

The flows of deoxyribonucleic acid and diaminopimelic acid and the digestibility of dietary fibre components at the terminal ileum, as indicators of microbial activity in the upper digestive tract of ileostomised pigs

The microbial markers deoxyribonucleic acid (DNA) and diaminopimelic acid (DAP) were used to compare the microbial biomass in the ileal digesta of ileostomised pigs with that in the faeces of intact pigs. Ileal and faecal (whole tract) digestibility of dietary fibre was also determined, to indicate the extent of microbial activity in the upper and lower digestive tracts. Six ileostomised pigs of 25 kg live weight and six intact pigs were given a human-type diet of bread, raw and cooked vegetable, cooked meat and dairy products for 12 days, total ileal digesta or faeces being collected over the final 4 days. The mean excretion of DNA in the ileal digesta (100.4 mg day −1) was significantly ( P < 0.01) greater than that in the faeces (48.2 mg day −1), while the mean ileal and faecal excretions of DAP (56.7 mg day −1 and 62.8 mg day −1, respectively) were not significantly different. On the basis of the mean DAP concentrations, the estimated concentrations of bacterial dry matter in ileal or faecal dry matter were 208 mg g −1 and 694 mg g −1, respectively. The digestibility of the dietary fibre components was significantly ( P < 0.001) greater when measured over the entire digestive tract than at the terminal ileum, though there was a considerable breakdown of pectin, hemicellulose and cellulose anterior to the end of the small intestine. It was concluded that there is a substantial and active microflora in the upper digestive tract of ileostomised pigs, and this may have implications for the determination of nutrient digestibility with surgically modified animals.

Urinary fluoride excretion in children using potassium fluoride containing salt or sodium fluoride supplements.

With the introduction of fluoridated domestic salt in France in 1986, questions have arisen with respect to its efficacy in caries prevention. It has been of interest to compare the urinary excretion of fluoride in children who consume fluoridated salt to that in children who take fluoride tablets. Ninety-three schoolchildren, 10-14 years of age, participated in the study and were divided into four groups: group I consumed fluoridated salt with every meal; group II ate at a school restaurant once a day and consequently consumed fluoridated salt at only their evening meal, as fluoridated salt is not authorized for use in collective restaurants; group III consisted of children taking fluoride tablets (1.0 mg F/day) exclusively, and group IV did not receive any systemic administration of fluoride for prevention and constituted a low-fluoride control group. Total 24-hour urine samples were collected from all subjects. The average daily urinary flow rates varied from 0.51 to 0.68 ml/min, but showed no statistically significant differences among the groups. The average urinary fluoride concentrations were 0.60, 0.30, 0.99, and 0.28 mg/l, respectively, for groups I-IV. The mean 24-hour urinary fluoride concentrations and excretion rates for children who consumed fluoridated salt at all meals (group I) were not statistically different from those using tables (group III). There were also no statistically significant differences between groups II and IV. The differences between urinary fluoride concentrations and excretion rates of groups I and III, as compared with group IV, were statistically significant.

Aminoguanidine ameliorates albuminuria in diabetic hypertensive rats.

We studied the effect of aminoguanidine, an inhibitor of advanced glycation product formation, on albuminuria in chronically diabetic spontaneously hypertensive rats. At the time of killing, there was no statistically significant difference in blood glucose concentration between the treated and untreated diabetic animals (18.2 +/- 0.69 mmol/l), nor was there any difference among the non-diabetic, diabetic untreated, and diabetic treated rats with respect to blood pressure (169 +/- 6.9 mm Hg). However, non-diabetic hypertensive animals had a mean quantitative 24-h urinary albumin excretion of 28 +/- 2 mg albumin/24-h, while untreated diabetic hypertensive animals averaged nearly four times that amount (106 +/- 3 mg albumin/24 h). Without affecting blood pressure, aminoguanidine treatment of diabetic hypertensive animals decreased the diabetic-associated elevation in urinary albumin excretion by 75% (48 +/- 2 mg/24 h). These data suggest than inhibition of advanced glycation product formation ameliorates the glomerular dysfunction caused by chronic hyperglycaemia.

Renal Involvement in Patients with Congenital Cyanotic Heart Disease

Patients with congenital cyanotic heart disease may develop a glomerulopathy with proteinuria and impaired renal function. In order to investigate this problem we conducted a study on 27 patients with uncorrected cyanotic heart disease who were between 1 day and 25 years old. As a consequence of hypoxaemia haematocrit was elevated to 57%. Proteinuria was above 150 mg/day/1.73 m2 body surface in 12 patients. Only one of 9 children under 10 years of age had pathological proteinuria presenting as isolated albuminuria. Seven out of 10 patients between 11 and 20 years had an elevated proteinuria with a glomerular pattern. Creatinine clearance was normal in these patients. All four patients above 20 years of age had a considerable glomerular proteinuria with a mean excretion of 5.7 g/24 h/1.73 m2 body surface. These patients suffered additionally from chronic cardiac failure and creatinine clearance was below the normal range. There was a clear relationship between pathological proteinuria and age of the patients and thus duration of hypoxaemia. Patients with pathological proteinuria had a significant higher erythrocyte count (7.3 +/- 1.3 vs 5.6 +/- 1.4 10(12)/l p less than 0.01) and a lower mean corpuscular haemoglobin. In summary, children with persistent congenital cyanotic heart disease have substantial risk of developing a glomerulopathy if the cyanosis remains unchanged for more than ten years.

Cross‐sectional epidemiological study on arsenic excretion in urine of children and workers in Greece

An investigation was undertaken to study the exposure of children in areas with different air pollution and of adults working in three different plants (lead processing, battery plant, oil refinery) using arsenic in urine as a biological parameter. The arsenic excretion of the children are in agreement with the air pollution in the investigated areas. The workers in the lead processing plant are found to have the highest urine excretion values of the three worker collectives. The mean excretion values is nearly ten times higher than that found in the normal population.

POSTTRANSPLANT NEOPTERIN EXCRETION IN RENAL ALLOGRAFT RECIPIENTS—A RELIABLE DIAGNOSTIC AID FOR ACUTE REJECTION AND A PREDICTIVE MARKER OF LONG-TERM GRAFT SURVIVAL

During the immediate posttransplant period, daily measurements of urinary neopterin, which is produced by stimulated macrophages, were evaluated in 294 consecutive recipients of renal allografts for their diagnostic value in acute graft rejection. The ability of mean and peak neopterin excretion values to predict long-term graft survival was analyzed on the basis of an eight-year follow-up. Immunosuppressive therapy (cyclosporine +/- prednisone versus azathioprine + prednisone) and initial nonfunction did not influence neopterin excretion. In patients with rejection episodes and in those with infections, neopterin levels were significantly increased. Diagnostic sensitivity and specificity with regard to rejection diagnosis were assessed for different levels of neopterin. By statistical analysis, a significant association between increased neopterin and higher risk of rejection was found, which was particularly pronounced in patients receiving cyclosporine. Increase in neopterin excretion preceded clinical rejection diagnosis by up to four days. Peak neopterin values above 800 mumols/mol urinary creatinine observed during the posttransplant period, were associated with significantly poorer graft survival. A multivariate analysis showed that peak neopterin levels, age of patients, and early posttransplant presence/absence of acute rejection were significant and independent joint predictors for long-term graft survival. Measurement of neopterin can be of help as an additional marker in early diagnosis of renal allograft rejection, and high neopterin values during the initial posttransplant period are associated with poorer long-term graft survival.