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A standard approach for visualizing multivariate networks is to use one or more multidimensional views (for example, scatterplots) for selecting nodes by various metrics, possibly coordinated with a node-link view of the network. In this paper, we present three novel approaches for achieving a tighter integration of these views through hybrid techniques for multidimensional visualization, graph selection and layout. First, we present the FlowVizMenu, a radial menu containing a scatterplot that can be popped up transiently and manipulated with rapid, fluid gestures to select and modify the axes of its scatterplot. Second, the FlowVizMenu can be used to steer an attribute-driven layout of the network, causing certain nodes of a node-link diagram to move toward their corresponding positions in a scatterplot while others can be positioned manually or by force-directed layout. Third, we describe a novel hybrid approach that combines a scatterplot matrix (SPLOM) and parallel coordinates called the Parallel Scatterplot Matrix (P-SPLOM), which can be used to visualize and select features within the network. We also describe a novel arrangement of scatterplots called the Scatterplot Staircase (SPLOS) that requires less space than a traditional scatterplot matrix. Initial user feedback is reported.

To examine the outcome of technical variant liver transplant techniques relative to whole organ liver transplantation in pediatric liver transplant recipients.Technical variant liver transplant techniques comprising split, reduced, and live-donor liver transplantation evolved to address the need for timely and size appropriate grafts for pediatric recipients.Analysis of data from the Studies of Pediatric Liver Transplantation (SPLIT) registry, a multicenter database of 44 North American pediatric liver transplant programs. The outcome (morbidity and mortality) of each of the technical variants were compared with that of whole organ recipients.Data were available on 2192 transplant recipients (1183 whole, 261 split, 388 reduced, and 360 live donor). Recipients of all technical variant graft type were significantly younger than whole organ recipients, but on average spent 2.3 months less on the waiting list. Thirty-day post-transplant morbidity was increased for each type of technical variant relative to whole organ (45.1% whole, 66.7% split, 65.5% reduced, 51.9% live-donor). Biliary complications (30 day: 7.5% whole, 18.8% split, 16% reduced, 17.5% live-donor) and portal vein thrombosis (30 day: 3.6% whole, 8% split, 8% reduced, 7.5% live-donor) were more common in all technical variant types. Graft type was an independent predictor of graft loss (death or retransplantation) in a multivariate analysis. Split and reduced (relative risk = 1.74 and 1.77, respectively) grafts had a worse outcome when compared with whole organ recipients.Technical variant techniques expand the pediatric donor pool and reduce time from listing to transplant, but they are associated with increased morbidity and mortality.

Background. Initiated in 1995, the Studies of Pediatric Liver Transplantation (SPLIT) registry database is a cooperative research network of pediatric transplantation centers in the United States and Canada. The primary objectives are to characterize and follow trends in transplant indications, transplantation techniques, and outcomes (e.g., patient/graft survival, rejection, growth parameters, and immunosuppressive therapy.) Methods. As of June 15, 2000, 29 centers registered 1144 patients, 640 of whom received their first liver-only transplant while registered in SPLIT. Patients are followed every 6 months for 2 years and yearly thereafter. Data are submitted to a central coordinating center. Results. One/two-year patient survival and graft loss estimates are 0.85/0.82 and 0.77/0.72, respectively. Risk factors for death include: in ICU at transplant (relative risk (RR) = 2.63, P

Enzymuria and specific proteinuria were examined over a period of 19 days in 4 groups of 5 rats: a control group, a non-diabetic polyuric group, a group of streptozotocin-induced diabetic rats treated with insulin as of the 10th day after the injection of the drug, and a similar group of untreated diabetic rats. Increased urinary excretion of β-N-acetyl-D-glucosaminidase, lactate dehydrogenase, and alanine aminopeptidase was observed shortly after the induction of diabetes. It was partly or totally reversible following insulin treatment. Nondiabetic polyuria had a slight effect on the excretion of alanine aminopeptidase only. The urinary excretion of β2-microglobulin also rapidly increased after the onset of diabetes to a level approximately 50 times the control values. This effect was largely reversible with insulin treatment and was absent in the nondiabetic polyuric group. A small but significant 3-fold increase in albumin excretion was also noted but was not affected by insulin treatment. We conclude that streptozotocin-induced diabetes causes an early tubular dysfunction that is unrelated to polyuria and is reversible upon insulin treatment. This tubular dysfunction is best revealed by the urinary excretion of the low molecular weight protein β2-microglobulin. Our results suggest that it would be of interest to further examine the usefulness of sensitive markers of tubular dysfunction, especially low molecular weight proteinuria, in the detection of early stages of diabetic nephropathy.Key words: diabetic nephropathy, enzyme, urine, proteinuria, β2-microglobulin, streptozotocin, insulin, rat.

OBJECTIVES: To assess environmental exposure to polycyclic aromatic hydrocarbons (PAHs) in the vicinity of a Söderberg aluminium reduction plant in Shawinigan, Canada with urinary 1-hydroxypyrene (1-OHP) as a biomarker. METHODS: Urine samples were collected from 20 non-occupationally exposed subjects living less than 500 m from the plant and from 20 controls living in Trois-Rivières, another industrial town 40 km from Shawinigan. Concentrations of 1-OHP were measured by high performance liquid chromatography (HPLC). RESULTS: Among controls, geometric mean (range) 1-OHP concentrations were 0.046 (0.012-0.116) mumol/mol creatinine in non-smokers and 0.125 (0.051-0.282) mumol/mol creatinine in smokers. Among exposed subjects, values were 0.103 (0.056-0.196) mumol/mol creatinine in non-smokers and 0.250 (0.112-0.448) mumol/mol creatinine in smokers. Excretion of 1-OHP was significantly higher in exposed subjects than in controls among non-smokers and smokers (P < 0.05). CONCLUSION: Based on urinary 1-OHP as a biomarker, it seems that living near an industrial point source of PAHs is associated with higher exposure. The health significance of this finding will require further investigation.

The manufacture of fibreglass reinforced plastic products may give rise to substantial peak exposures to styrene. Such exposure patterns need further consideration in terms of styrene neurotoxicity. The aim of this study was to evaluate the neurotoxic effects of short-term peak exposures in volunteers, at levels respecting the Quebec occupational exposure limits (8 hours time weighed average of 213 mg/m3 and 15 min average of 426 mg/ m3). The volunteers had not been previously exposed to styrene and they had no documented exposure to known neurotoxicants during the study. Twenty-four volunteers were exposed to five exposure scenarios during 6 hours: a, stable exposure to 106 mg/m3; b, variable exposure with a mean concentration of 106 mg/m3 with four 15 min peaks mounting up to 213 mg/m3; c, stable exposure to 213 mg/m3; d, variable exposure with a mean concentration of 213 mg/m3 and four peaks of 426 mg/m3 and e, two stable exposures to 5 mg/m3 (control). Before and after each exposure scenario, volunteers were submitted to a battery of sensory tests (visual and olfactory), neuropsychological tests (reaction time, attention, memory, psychomotor function), and self-evaluation questionnaires (mood and symptoms) in a test-retest design. The results show that the different exposure scenarios involving peak exposures did not influence either the performance to any test or subjective signs and symptoms. However, due caution must be exercised in extrapolation of the current results to occupational exposure since only acute exposures were tested and volunteers were at rest during exposure, which resulted in lower doses than those experienced by physically active workers.

In an attempt to define a tolerable daily intake (TDI) for molybdenum based on a toxicological risk analysis approach, a large literature survey was conducted. In man, absorption of molybdenum after oral intake is in the range of 28-77% and urinary excretion is 17-80% of the total dose. A low order of toxicity of molybdenum compounds has been observed in humans. However, with the available data, it is not possible to calculate any dose-response or dose-effect relationships. Because molybdenum toxicity is associated with copper intake or depleted copper stores in the body, humans who have an inadequate intake of dietary copper or some dysfunction in their copper metabolism that makes them copper-deficient could be at greater risk of molybdenum toxicity. In the absence of relevant human studies, animal studies were evaluated for the derivation of the TDI. Effects of Mo on reproduction and foetal development were found to be critical effects observed in rats and mice. A dose-response relationship was observed in a study by Fungwe et al., with a 'no observed adverse effect' level (NOAEL) and a 'lowest observed adverse effect' level (LOAEL) of 0.9 and 1.6 mg Mo kg(-1) day(-1), respectively. Applying uncertainty factors of 10 for intraspecies and 10 for interspecies differences to the NOAEL, a TDI of 0.009 mg Mo kg(-1) day(-1) was calculated. The TDI is given a medium confidence rating. This TDI is more than double the upper limit of adequate intake for adolescents and adults that was derived from the Mo content of the average diet in the USA.

beta 2-microglobulin (beta 2-m) was measured in the urine of rats by a specific immunoassay based on latex particles agglutination. The excretion of this protein was compared to the excretion of the enzyme beta-N-acetyl-D-glucosaminidase (NAG), albumin and amino acids in rats treated with either a single dose of sodium chromate (5 and 10 mg kg-1), repeated doses of gentamicin (5 and 20 mg kg-1), or cadmium (1 mg kg-1), and in aging rats (from 2 to 20 months). All treatments resulted in an early increased excretion of beta 2-m indicative of functional alterations of the proximal tubular cells. An increased NAG excretion was observed only at the highest dose of chromate and in the cadmium model but the relative increases of beta 2-m were much larger (up to 200 times the control values against four times the control values for NAG). From 2 to 20 months of age, urinary beta 2-m increases by a factor of four. Aminoacids excretion showed little sensitivity in the various models. Albumin showed little variations in purely tubular or in the tubular phase of renal injury but the chronic progressive nephrosis of aging rats caused a 40-fold increase in its excretion between 2 and 20 months of age. Therefore urinary beta 2-m, albumin and albumin/beta 2-m ratio provide useful tools in the assessment of nephrotoxicity and of its mechanisms in various experimental models.

The urinary excretion of beta 2-microglobulin, retinol-binding protein and albumin was measured in 65 workers exposed to styrene at levels averaging 50 percent of the current threshold limit value (215 mg/m2) for 1-13 years (mean: 6 years). By comparison with a control group matched for age and socioeconomic status, no significant difference was observed in the urinary excretion of proteins. In rats, styrene was weakly nephrotoxic. No functional or morphological renal change could be disclosed in rats exposed to 565 mg of styrene/m3, 5 days/week for 13 weeks. The repeated i.p. injection of 1 g styrene/kg (1/5 of oral LD50) for 10 days induced only a slight tubular dysfunction as evidenced by a 5-fold increase in beta 2-microglobulinuria. Altogether, these epidemiological and experimental data suggest that the current threshold limit value for styrene (215 mg/m3) proposed by the American Conference of Governmental and Industrial Hygienists does not entail any risk of renal toxicity.

We describe a latex particle agglutination assay for detecting circulating antibodies against laminin, a noncollagenous glycoprotein of basement membranes. Polystyrene latex particles on which laminin has been adsorbed are incubated with serum for about 25 min at 42-45 degrees C. The agglutination is then measured by counting residual unagglutinated particles. Polyethylene glycol 6000 enhances the agglutination. The assay is fully automated, yielding results in about 45 min, for 50 samples per hour. Addition of purified laminin abolishes the agglutination of laminin-coated particles in practically all positive sera. The anti-laminin antibody titers obtained by this latex immunoassay and by radioimmunoassay correlated well in 161 sera from patients with suspected or established renal diseases. The agglutination assay more frequently gave positive results for cases of glomerulonephritis with linear deposits (20/22 cases) than for glomerulonephritis with granular deposits (7/68) or glomerulonephritis with no glomerular deposits (2/13). The finding of low anti-laminin antibody titers in sera from about 15% (34/230) of the healthy subjects suggests that these autoantibodies are pathogenic only in certain circumstances.

Inhalation exposure of male Sprague-Dawley rats to an industrial white-spirit solvent composed of a C10–C12 mixture of branched-chain unsubstituted satured aliphatic hydrocarbons at 6500 mg/m3 for over 9 months resulted in decreased urinary concentrating ability, decreased net acid excretion following a mild ammonium chloride load and increased urinary lactate dehydrogenase (LDH) activity, whereas urinary s-N- acetyl- d -glycosaminidase (NAG) activity remained normal. These observations suggest the existence of distal tubular alteration in the rat kidney.

To study the effect of gentamicin on the renal uptake of proteins, Sprague-Dawley female rats were intravenously injected with solutions containing unlabeled human beta 2-microglobulin (beta 2-m), retinol-binding protein, and increasing amounts of gentamicin (from 0.063 up to 31.5 mg/kg). The concentrations of human proteins and that of endogenous beta 2-m, albumin, and IgG in the urine collected during the 2 hr following the injection were determined by immunoassays. Gentamicin transiently increased the urinary excretion of rat and human beta 2-m in a dose-dependent manner. The mean relative increase of rat beta 2-m excretion ranged from 2 at a gentamicin dose of 0.06 mg/kg up to 500 at a gentamicin dose of 31.5 mg/kg. By contrast, the urinary excretion of other proteins was only increased by a factor of 2 to 5 at the highest dose of gentamicin. The relative increase of the urinary excretion of proteins was positively correlated with the fractional reabsorption of the proteins by the rat kidney. The inhibitory effect of gentamicin on the renal uptake of protein was very similar to that observed in rats injected with polycationic proteins like lysozyme and cytochrome C. These observations, combined with the fact that gentamicin, like proteins, enters the tubular cell by adsorptive endocytosis, strongly suggest that this drug competes with proteins for common binding sites on the apical tubular membrane and for subsequent endocytosis. Furthermore, the iv injection of large amounts of gentamicin and polycationic proteins induces a lysosomal enzymuria which very likely is a manifestation of an increased exocytosis.

The renal uptake of proteins: A nonselective process in conscious rats. The selectivity of the renal reabsorption of proteins has been investigated by competition experiments in conscious rats. The animals were intravenously injected with increasing doses of proteins over a wide range of net charge and size, including lysozyme, cytochrome C, metallothionein, β2-microglobulin, retinol-binding protein, albumin and IgG. The urinary excretion of exogenous proteins injected concomitantly (humanβ2-microglobulin, retinol-binding protein, albumin and/or egg white lysozyme depending on the experiment) and of rat β2-microglobulin, albumin and IgG was determined with specific immunoassays. The results show that low molecular weight cationic proteins and low or high molecular weight anionic proteins can increase each other's urinary excretion. Several observations strongly suggest that these effects result from a competitive inhibition of renal uptake. The phenomenon is dose-related in most cases and, as evidenced by cytochrome C injection, transient, reproducible and saturable. In addition, the injected proteins induce a tubular type proteinuria irrespective of their net charge and size. In the case of cationic proteins, this finding excludes the possibility of an enhanced glomerular permeability due to a partial neutralization of the glomerular polyanion which, as demonstrated with protamine sulfate, entails a glomerular type proteinuria. These quantitative data on the mutual inhibition of renal uptake of a wide spectrum of specific proteins lead us to challenge the concept of charge- and size-selective tubular reabsorption of proteins, and to postulate that proteins filtered through the glomeruli are taken up by common tubular endocytotic sites irrespectively of their physicochemical features. As demonstrated by the ability of β2-microglobulin and IgG to inhibit the uptake of lysozyme, the affinity of a protein for reabsorption sites is not simply related to its size and net positive charge. Evidence is also presented that proteins, when administered intravenously at high doses, induce a lysosomal enzymuria most likely reflecting a stimulated exocytosis.

The effect of a previous chronic exposure to cadmium, lead or inorganic mercury on the nephrotoxic potential of gentamicin was investigated in female Sprague-Dawley rats. A daily dose of 10 mg gentamicin/kg body weight/day was administered for 21 days to rats having a renal load of 168 micrograms Cd, 35 micrograms Pb or 129 micrograms Hg/g whole kidney. Urine analysis suggests an attenuation of the nephrotoxic potential of gentamicin while a microscopical examination of kidneys indicates a superimposition of the effects of the metals and the antibiotics. The only clear interaction observed consists in a reduction of gentamicin accumulation in the cortex of cadmium-treated animals. It is concluded that none of the metal pretreatments potentiates the nephrotoxic effects of gentamicin.

Polychlorinated dibenzo-p-dioxins (PCDDs) and other organic compounds are solvent extracted from 10- to 20-g samples of fly ash from municipal incinerators with 200 mL of benzene using ultrasonic agitation for 1 h. A convenient filtering device is used to separate fly ash and solvent which is then concentrated to 100 ..mu..L using a rotary evaporator. Extracts are analyzed directly by gas chromatography/mass spectrometry, including selected ion monitoring for PCDDs. Results from five replicate analyses of a fly ash sample yielded averages and standard deviations (ng/g) for the tetra-to octachlorinated dibenzo-p-dioxins of 8.6 +- 2.2, 15.0 +- 4.0, 13.0 +- 3.4, 3.2 +- 1.0, and 0.4 +- 0.1, respectively. 2 tables, 3 figures.

Fly-ash samples from municipal incinerators in Canada and Norway were analyzed for polychlorinated dibenzo-p-dioxins using gas chromatography/mass spectrometry preceded by fractionation on column chromatography. Qualitative and quantitative differences in the organic compounds identified were found between the two samples. Many of the same dioxin congeners were present in both samples; however, tetrachlorodibenzo-p-dioxins were only detected in the Canadian sample.

Prolonged inhalation exposure to 6.5 mg/l of an isoparaffinic solvent consisting of saturated aliphatic hydrocarbons (SAHC) resulted in both functional and morphological renal changes in male rats to the exclusion of female or castrated rats. Functionally, the increased excretion of lactate dehydrogenase in the absence of an increased beta-N-acetyl-D-glucosaminidase excretion together with a decreased urinary concentrating ability upon water deprivation and slower antinatriuretic response when the sodium intake is abruptly reduced, suggest a distal tubular alteration. beta 2-Microglobulin excretion is unchanged indicating good proximal tubular cell function. The increased excretion of albumin and slightly lowered glomerular filtration rate suggest a moderate glomerular impairment. Light microscopy shows prominent hyaline droplet accumulation in proximal tubular cells and a few scattered foci of regenerative epithelia in both proximal and distal cells of the deep cortex. The urinary clearance of the major male rat urinary protein, alpha 2u-globulin, is similar in control and exposed rats but the latter have a 10-fold greater renal accumulation of this protein while the hepatic levels are identical in both groups. It is concluded that SAHC exposure causes moderate and reversible tubular and also glomerular changes in the male rat kidney.

In workers chronically exposed to cadmium and without signs of renal insufficiency, plasma proteins with molecular weight ranging from 11,800 to 450,000 are excreted in greater amount in urine. Increased urinary excretion of low and high molecular weight proteins can occur independently. Because of its greater stability in urine and provided a sensitive immunological technique is used, the determination of retinol-binding protein is a more practical and reliable test of proximal tubular function than beta 2-microglobulin. The evaluation of renal function of workers removed from cadmium exposure indicates that cadmium-induced renal lesions, albeit of slow progression, are not reversible when exposures ceases. In workers chronically exposed to cadmium or removed from cadmium exposure, metallothionein in urine is directly correlated with cadmium in urine but not with cadmium in blood or years of cadmium exposure. The association between cadmium in urine and metallothionein in urine is independent of the status of renal function and the intensity of current exposure to cadmium. Whereas the repeated IP injection of high doses of cadmium to rat gives rise to a mixed or tubular type proteinuria, the prolonged oral administration of cadmium results mainly in the development of a glomerular type proteinuria. The former is usually reversible after cessation of treatment whereas the latter is not. Circulating antiglomerular basement membrane antibodies have been found in man and in rat chronically exposed to cadmium. The pathogenic significance of this finding deserves further investigation. Images FIGURE 5.

j Summary: A sensitive immunoassay based on latex particle agglutination for the measurement of circulating j IgE-containing complexes is described. In this method, the anti-IgE-coated particles are incubated with !' diluted serum and the resulting agglutination is quantified by turbidimetry or particle counting. In the latter \ Version, the assay is fully automated in a continuous flow System. IgE-containing complexes were detected i in all tested sera. Increased concentrations were observed in about 80% of the subjects with elevated serum j IgE. However, high levels of IgE-complexes may also be found in subjects with a normal or even a very low j serum concentration of IgE. The same latex immunoassay can be used for the determination of total IgE, after pepsin digestion of the -globulin fraction of the serum. The results obtained correlate well with those found with a sandwich radioimmunoassay (r = 0.91, n = 83). The present method, however, yields a greater number of significantly positive results than the radioimmunoassay, probably because of its ability to detect IgE entrapped in circulating complexes.

We describe a latex particle agglutination assay for detecting circulating antibodies against laminin, a noncollagenous glycoprotein of basement membranes. Polystyrene latex particles on which laminin has been adsorbed are incubated with serum for about 25 min at 42-45 degrees C. The agglutination is then measured by counting residual unagglutinated particles. Polyethylene glycol 6000 enhances the agglutination. The assay is fully automated, yielding results in about 45 min, for 50 samples per hour. Addition of purified laminin abolishes the agglutination of laminin-coated particles in practically all positive sera. The anti-laminin antibody titers obtained by this latex immunoassay and by radioimmunoassay correlated well in 161 sera from patients with suspected or established renal diseases. The agglutination assay more frequently gave positive results for cases of glomerulonephritis with linear deposits (20/22 cases) than for glomerulonephritis with granular deposits (7/68) or glomerulonephritis with no glomerular deposits (2/13). The finding of low anti-laminin antibody titers in sera from about 15% (34/230) of the healthy subjects suggests that these autoantibodies are pathogenic only in certain circumstances.

The renal handling of human beta 2-microglobulin (beta 2-m) was investigated in normal rat and in rat with cadmium-induced renal damage. Cadmium was administered either in drinking water at a concentration of 100 ppm for up to 16 months or by i.p. injection of 1 mg Cd/kg, five times a week for up to 4 months. When renal dysfunction has developed, namely after 2 and 10 months of the i.p. and oral treatment respectively, unlabelled human beta 2-m was injected intravenously and its disappearance in serum and its urinary excretion were studied by means of a sensitive immunoassay. In serum, the level of beta 2-m drops by about 90% during the 10 first min, then declines more slowly with a half life around 20 min. Serum disappearance curves of beta 2-m in normal and cadmium-treated rats did not differ markedly. The amount of beta 2-m recovered in urine during the 4 h following the injection averaged 0.03% of the injected dose in normal rats. It increased on the average to 10% in rats treated i.p. with 1 mg Cd/kg for 3 months. However, in rats given 100 ppm Cd per os for 10 months, this amount averaged only 0.14%. A similar value was observed 5 months later, although at that stage, the critical level of cadmium in kidney cortex had been reached for 6-7 months. These data which were in accordance with the disturbances of the other renal parameters measured in cadmium-treated rats indicate that: 1) human beta 2-m is reabsorbed by rat kidney at a similar rate as by human kidney; 2) if the occurrence of cadmium tubulopathy is concomitant with the saturation of cadmium-binding sites in kidney, its severity depends greatly on the rate at which cadmium reaches the saturated kidneys.

To explain the occurrence of tubular and glomerular proteinuria in patients with primarily tubular or glomerular dysfunction, it is usually assumed that the mechanisms responsible for the renal tubular transport of small and large proteins are different. The present in vivo study does not support this hypothesis since it clearly shows that small and large proteins (e.g., beta 2-microglobulin and albumin) can compete for renal uptake. Our results lead us to postulate the existence of common tubular reabsorption sites for which proteins exhibit different affinities depending on their charge, size and conformation.

Rat beta 2-microglobulin has been isolated from the urine of rats pretreated with sodium chromate. The purified protein was used to raise antisera in two rabbits. Treatment of the antisera with ammonium sulphate followed by gel chromatography led to an immunoglobulin fraction which was used to coat latex particles by physical adsorption. The latex suspension was used in an automated system including an optical particle counter to analyse the protein in serum, urine and cerebrospinal fluid. Serum contains 5.8 mg of beta 2-microglobulin/l, of which 33% is found as a 55000 dalton complex while 66% is present as the 'free' protein. The daily urinary excretion of beta 2-microglobulin in females is about 2 micrograms of which 7% is found to be a 65000-dalton complex while 92% is the free protein. From this, it can be calculated that the fractional urinary excretion of beta 2-microglobulin is about 0.03%. The cerebrospinal fluid contains about 1 mg of beta 2-microglobulin/l. Preliminary tests also suggest that the method can be adapted for non-automated turbidimetric detection. In the automated assay, the within- and between-assay coefficients of variation are less than 10% for the three biological fluids tested. The analytical recovery in the urine is 93%. In urine, beta 2-microglobulin undergoes proteolytic degradation at pH below 6. This does not represent a serious drawback to its use as a sensitive index of tubular function since in most experimental circumstances, rats excrete urine with a pH above this value.

Short-term exposure to certain solvents, such as several halogenated hydrocarbons, petroleum distillates, ethylene glycol, ethylene glycol ethers, and diethylene glycol, may cause renal tubular necrosis. Tubular lesions with metabolic acidosis have been reported in addicts inhaling solvent vapor (eg, toluene). A Goodpasture's syndrome may be induced by acute or subacute exposure to solvents, but its incidence is rare. No adequate proof is yet available that repeated exposure to nonsubstituted organic solvents may lead to the development of different types of chronic glomerulonephritis, but the available epidemiologic data are suggestive of the existence of such an association. Only a few solvents have been reported to act on the hematopoietic system of humans. The hematotoxicity (aplastic anemia, leukemia) of benzene is well established. Some ethylene glycol ethers are also toxic to bone marrow.

Female Sprague-Dawley rats received phenacetin or aspirin at average daily doses of 135 and 27 mg/kg respectively in the diet and either demineralized water (DMW) or a 100 ppm cadmium (Cd) solution as their drinking water for 12 months. This dose of Cd produced borderline tubular toxicity, as measured by the excretion of IV-injected human beta 2-microglobulin. The kidney accumulation of Cd just reached the critical level of 200 ppm in all groups at the end of the study. The various treatments did not significantly affect growth, creatinine clearance, urine osmolality and the urinary excretion of beta-N-acetyl-D-glucosaminidase and aminoacids. No interaction resulted from the concomitant administration of analgesics and Cd. Both aspirin subgroups (receiving DMW or Cd) showed an attenuation of the age-related decline of the renal function as revealed by a lower urinary excretion of albumin and total protein. The accentuation of the mesangial matrix seen upon aging was also partly inhibited in the aspirin rats.

The relationships between the urinary excretion of ferritin and that of albumin, β2-microglobulin and retinol-binding protein were studied in 60 healthy subjects and in 34 subjects exposed to a nephrotoxic agent (cadmium). The results suggest that the ferritin present in urine originates mainly from the kidney and its concentration depends on both the renal store of ferritin and the importance of tubular cell damage.

We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

Describes the design, use, and advantages of a gas chromatography / mass spectrometer / computerized data system.

Biological monitoring (BM or biomonitoring) deals with the assessment of individual human exposure, effect and susceptibility to occupational risk factors. It is a fundamental tool in occupational health risk assessment (OHRA) and occupational health practice (OHP) and it has become one of the most, if not the most active area in occupational health (OH) research today. From the few hundred BM papers published in the 80s, there are now several tens of thousand papers published in the peer review literature each year, and the trend is still rising exponentially. As a result, BM has become a priority for the Scientific Committee on Occupational Toxicology (SCOT) of the International Commission on Occupational Health (ICOH). Moreover, there has been a long-term interest in biological monitoring by other SCs of ICOH such as the Scientific Committees on Toxicology of Metals (SCTM) and on Rural Health (SCRH). Despite its current popularity, though, BM is not always correctly used or interpreted by those involved in OHRA or OHP. The present review has been prepared to fill this gap and to help preventing misuse and misinterpretation of data. Although the document is meant to be a reference primarily for those involved in OH research and/or practice, it might become of interest for a wider audience within and outside ICOH, including scientists, occupational physicians, industrial hygienists and occupational or public health professionals in general, involved in chemical risk assessment for occupational health. The mission of SCOT and also of other SCs of ICOH, such as SCTM and SCRH, is indeed to promote the advancement and diffusion of knowledge on biological monitoring and other relevant occupational toxicology aspects and to make them available and useful to the entire OH scientific community. All articles retrieved as of 3 January, 2007 as "Review" with the combined key words "biological monitoring" in PubMed from 2000 to 2007 have been scanned individually. This yielded a total of 1400 articles from a grand total of 2486 (excluding limitation on year of publication). When the title was related to human occupational biological monitoring, the abstract was read and its content was included. Articles outside the 2000-2007 time frame or that are not classified as "Review" in PubMed have also been included, when relevant. The review is in four parts: (a) the introduction, containing the basic principles and definitions of BM and the different types of biomarkers (BMK), their toxicological significance, practical use and limitations, (b) the methodological and analytical aspects of BM in exposed workers, (c) the interpretation and management of BM data, including a number of recommendations to be considered when planning, performing and interpreting BM results and, finally, (d) the ethical aspects of BM. A list of key references to relevant papers or documents has been included. The BM of specific chemicals or groups of chemicals is outside the purpose of the review. The document is aimed to represent the state of the art on biological monitoring in occupational risk assessment. We expect that reference to its content will be made, whenever appropriate, by those involved in occupational health practice and research when dealing with BM issues. The document is not meant, though, to represent a rigid nor a permanent set of rules and it will be periodically updated according to new developments and any significant advance in BM science. Any part of the document, therefore, is open to suggestions by scientifically qualified persons or institutions officially involved in BM and comments should be sent directly to the authors. A preliminary draft of the document has been presented at the 7th International Symposium on Biological Monitoring, Beijing, 10-12 September, 2007.