MR lymphography using iron oxide nanoparticles in rats: pharmacokinetics in the lymphatic system after intravenous injection.

The objective of the study was to quantify the kinetics of the superparamagnetic nanoparticle ferumoxtran (AMI 227, Sinerem(R), Combidex(R)) in the efferent lymph of the subdiaphragmatic lymph nodes and in various node groups of the rat to elucidate the uptake mechanism. The thoracic lymph duct was catheterized in 24 rats after an IV injection of 40 micromol Fe/kg ferumoxtran. Three rats were studied at several time points between 1.5 and 24 hours. At each time point, 0.3 ml of lymph were collected over 45 minutes. Lymph nodes were differentiated into five groups. The iron concentration in the samples and in plasma was measured by relaxometry at 0.47 T and atomic absorption spectrometry. Cytology was performed on the lymph. High concentrations of nanoparticles were found in the thoracic lymph soon after injection (90 minutes). No particle was found in the lymph cells, indicating that ferumoxtran was extracellular in the lymph fluid. The maximum concentration was reached later in all node groups, at 12 hours, and then plateaued. The transcapillary pathway and subsequent lymph drainage of the particles seem to play a major role in the delivery to the lymph nodes.

Assessment of erythrocyte cholinesterase activity in victims of smoke inhalation.

BACKGROUND: The nature of the toxic gases that cause death from smoke inhalation is incompletely understood, and the mechanisms leading to incapacitation remain to be determined. Thermal degradation products of various compounds, including phosphorous-based fire retardants, are suspected capable of impairing human cholinesterase activity. The aim of this study was to measure the erythrocyte cholinesterase activity in victims of smoke inhalation. METHODS: We prospectively measured the erythrocyte cholinesterase activity in blood samples obtained at the scene of residential fires from 49 fire victims. We compared the results with those in an unmatched group of 45 persons with acute drug poisoning. RESULTS: The median (25th-75th percentiles) erythrocyte cholinesterase activity in the 49 fire victims, 1968 IU/L (1660-2276), was significantly lower than in the 45 control subjects 2460 IU/mL (1968-2890), (p = 0.0004). There was no significant difference of the red blood cell counts or plasma protein levels between the 2 groups, while the hematocrit was significantly greater in the fire victims than in the drug-poisoned patients. There was a significant correlation between blood cyanide and carbon monoxide concentrations in the fire victims (r = 0.494, p = 0.002). There was no correlation between erythrocyte cholinesterase activity and either blood cyanide (r = 0.11, p = 0.44) or blood carbon monoxide concentrations (r = 0.04, p = 0.78). CONCLUSIONS: We found a significantly lower level of erythrocyte cholinesterase activity in victims of residential fires, when compared with a convenience sample of hospitalized poisoned patients. Despite the limitations of the study, investigations of the toxic gases potentially responsible for impairment of cholinesterase activity and the clinical significance of this lower enzymatic activity merit further investigation.

Acute selenium poisoning.

Reports of acute human selenium toxicity are rare. We report 2 new cases. One patient ingested a mouthful of selenic acid (30 g/L); he only suffered mild gastrointestinal disturbances. Serial measurements of plasma selenium concentrations were performed. The first plasma level was obtained 3 h after ingestion and was the highest (931 micrograms/L); plasma concentrations subsequently decreased with a half-life of 17.5 h. The second patient ingested 1.7 g of sodium selenite. He suffered severe gastroenteritis, had transient electrocardiographic changes and developed a slight elevation of serum bilirubin. The first serum concentration measurement was performed 3 h after ingestion; the selenium level was 2.716 micrograms/L. These data are compared to those from other published cases. The prognostic significance of the blood selenium concentration is discussed.

Continuous flow quantification of total mercury in whole blood, plasma, erythrocytes, and urine by inductively coupled plasma atomic emission spectroscopy.

Mercury determination in blood and urine can be performed by inductively coupled plasma atomic emission spectroscopy (ICPAES) after dilution in an ammonia buffer and reduction by sodium borohydride. The proposed method does not need an oxidative mineralization. The sample is not nebulized into the torch, but the mercury vapor, after collection in a reactor vial, is swept into the plasma by the argon carrier gas using the described glass apparatus.

2,3-Dimercaptosuccinic acid treatment of heavy metal poisoning in humans.

14 patients with heavy metal poisoning received 2,3-dimercaptosuccinic acid (DMSA). 12 subjects were given 30 mg/kg/day for 5 days; 1 subject was started on a lower dose because of a history of atopy; another subject was treated for 15 days because of very high initial blood lead concentrations. In the 9 subjects who had lead poisoning, DMSA decreased blood lead concentrations by 35 to 81%, and induced a 4.5- to 16.9-fold increase in mean daily urinary excretion of the metal. In the acutely arsenic-poisoned case, the plasma arsenic concentration on day 7 was half the pretreatment value, while no clear decrease was observed in a chronically exposed subject. In 3 mercury cases, DMSA increased daily mercury urinary excretion 1.5-, 2.8- and 8.4-fold, respectively, while blood mercury concentrations remained below detection limits. No serious side effects were observed and 3 weeks after administration of the drug the clinical condition of all subjects was either stable or improved. These results indicate the efficacy of DMSA for lead poisoning in humans and provide a rationale for further investigating its usefulness in mercury and arsenic poisoning cases.

Occurrence of manganese, copper and zinc in myelin. Alterations in the peripheral nervous system of dysmyelinating trembler mutant are at variance with brain mutants (quaking and shiverer).

Mn, Cu and Zn were present in mouse brain at concentrations that were 54, 4 and 14 times higher than in serum. In comparison with control animals, Mn was nearly normal in both quaking and shiverer dysmyelinating mutants. Cu was slightly higher in shiverer; Zn was higher in quaking only when expressed on a dry weight basis. The peripheral nervous system contained lower amounts of Mn, Cu and Zn than brain, (1 6 , 1 8 and 1 2 respectively). All three metals were much higher in trembler (4, 3 and 2-fold increase, respectively). Although higher in shiverer and quaking, Mn did not differ significantly from control. Cu and Zn were similar to control in the sciatic nerve of quaking and shiverer. Brain myelin contained Mn, Cu and Zn concentrations that were slightly smaller than those found in the whole brain. Mn and Cu were higher in the myelin from shiverer by approx. 2- and 3-times, whereas Zn was two-fold reduced. It is speculated that such metals play a role in membrane as cofactors of enzymes, especially those in control of free radical damage, and possibly also in membrane structures as phospholipid counterions.

Arterial-venous plasma concentration differences of meprobamate in acute human poisonings.

Arterial-venous plasma concentration differences of meprobamate were studied on admission of acute overdose in man. The patients were divided in two groups. In the control group (n = 25) two successive blood samples were collected from the same vessel. In the study group (n = 35) femoral arterial and venous blood samples were collected simultaneously. In the control group the differences were not significant. In the study group the differences were statistically significant (P less than 0.01). The present study suggests that the origin of blood samples should be stated for toxicological studies and that the toxicokinetics may be more complex than those recognized previously.

[Increase of blood lead in alcoholism. Relation with blood pressure]. / Elévation de la plombémie au cours de l'alcoolisme. Relation avec la pression artérielle.

Blood lead levels and blood pressure were measured on admission in 161 chronic alcoholic patients (121 men and 40 women) hospitalized for detoxification. The mean lead level was 280 micrograms/l and the highest value, in one patient, was 725 micrograms/l. These figures were as high as those of subjects under occupational exposure to lead. Blood lead level was correlated with blood pressure, and the statistical correlation appeared to be independent. Blood lead level was also correlated with serum gamma-glutamyl-transferase concentration and with the mean corpuscular volume. Wine drinkers had higher blood lead level than beer and/or liquor drinkers (mean: 298 micrograms/l versus 225 micrograms/l respectively), which fits with the higher lead content of wine.

Histomorphometric evidence of deleterious effect of aluminum on osteoblasts.

Bone histomorphometry was performed in 26 hemodialyzed patients to study the relation between the dynamic parameters of bone formation and aluminum deposition. Patients were divided into two groups according to whether bone formation rate at tissue level (Svft) was above or below normal: 0.089 mu 3/mu 2 per day. The 12 patients who constituted group II, defined by a Svft less than 0.089 mu 3/mu 2 per day, had markedly decreased extent of double-labeled surfaces (m = 1.3 +/- 6.5%), and these were absent in 8 of 12 patients. Osteomalacia, defined by decreased formation with increased mean osteoid thickness (greater than 15 micron), was present in only 3 of 12 patients in group II. The 14 patients who constituted group I, defined by a Svft greater than 0.089 mu 3/mu 2 per day, had both increased total labeled surfaces and mineralization rate. Osteomalacia was present in none of the group I patients. In trabecular bone, group II patients had increased stainable aluminum deposition, compared to group I patients, whether estimated as total stainable aluminum (2.16 +/- 1.34 vs 0.17 +/- 0.28 mm/mm2) or stainable percent of trabecular surfaces (42 +/- 19 vs 4 +/- 5%). This last parameter was inversely related to osteoblastic surfaces (r = -0.49, n = 26, P less than 0.01) and total labeled surfaces (r = -0.72, n = 26, P less than 0.01). Therefore, massive aluminum deposition was not invariably associated with impaired mineralization but with decreased formation due to decreased extent of active formation surfaces. In the group I patients, moderate aluminum deposition was not associated with the mineralization arrest observed in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Multifactorial low remodeling bone disease during cyclic total parenteral nutrition.

The physiopathology of metabolic bone disease described during long term total parenteral nutrition is poorly understood. We therefore prospectively assessed bone status of seven adult patients [mean age, 42 +/- 16 (SD) yr] treated with cyclic total parenteral nutrition for a period of 7 +/- 2 (SD) months. All patients had hypercalciuria (381 +/- 96 mg/day) associated with negative calcium balance in six of seven patients (-49 +/- 120 mg/day). A correlation was found (r = +0.74, P less than 0.01) between protein intake and calciuria. Two patients developed slight transient hypercalcemia. Serum magnesium and phosphate levels remained within the normal range. A high aluminum load due to the added phosphate solution (253 +/- 84 micrograms/day) was associated with increased serum aluminum levels (52 +/- 38 micrograms/liter). Normal serum levels of 25 hydroxyvitamin D (12 +/- 7 ng/ml) and low normal 1,25 dihydroxyvitamin D levels (21 +/- 8 pg/ml) were found. Serum PTH was normal in five and increased in two of the seven patients. However, in these two patients skeletal unresponsiveness to the action of PTH was found. A new histomorphometric picture of bone was observed; it consisted of a markedly reduced bone formation with subnormal osteoclastic activity leading to a low trabecular bone volume. No osteomalacia was found. The aluminum load may have played a role in these bone defects. The hypercalciuria with negative calcium balance was attributed to the cyclic amino-acid delivery during TPN.

[Subclinical alcoholic optic neuritis without vitamin deficiency]. / Névrites optiques alcooliques infra-cliniques sans carences vitaminiques.

Vitamin B1, Folic acid Vitamin B12, whole blood Lead level, and plasma Zinc level were determined in 82 patients admitted to an alcoholism rehabilitation program. Each patient was examined for an optic neuritis. Thirty-two of the patients had sub-clinical abnormalities suggestive of optic neuritis like dyschromatopsias and/or field visual defects. No differences were found in the blood levels of Vitamin B1, Folic acid, and Vitamin B12 between the 32% affected and the 68% unaffected subjects. Moreover vitamins blood levels were found to be within the limits of normal values in both groups. A negative correlation between whole blood Lead levels and plasma Zinc levels was found. When an optic neuritis occurs the lead level tends to be higher and the Zinc lower. Abnormalities of the more usual alcoholism tests: gamma glutamyl Transpeptidase (gamma GT), mean red cell volume (V.G.M.) and glutamic Oxaloacetic transferase (T.G.O.), were more pronounced in alcoholics with optic neuritis.

Arterio-venous plasma concentration differences in amitriptyline overdose.

The aim of this study was to determine whether femoral arterio-venous plasma concentration differences (AVD) of amitriptyline exist during acute intoxication in man. All patients studied were comatose and were divided into a control group who had two successive blood samples drawn from the same vessel and a study group who had samples drawn from the femoral artery and vein simultaneously. Serial plasma concentrations of amitriptyline were measured by gas liquid chromatography. In each group the differences were assessed by means of the Wilcoxon matched pairs test. In the control group (n = 13) there were no differences (T = 31, n = 12). In the study group (n = 24) the AVD were significantly different (T = 52, n = 23). For amitriptyline, the arterial or venous origin of blood samples for toxicological studies must be stated.

[Sensitivity and specificity of lead poisoning detection tests]. / Sensibilité et spécificité des tests de dépistage du saturnisme.

The results of biochemical tests used for the supervision of factory workers exposed to lead (notably lead serum levels, urinary aminolevulinic acid (ALA) and punctuated red cells) were compared in 90 patients. The reference test used to evaluate the sensitivity and specificity of these examinations was EDTA-induced lead urinary excretion. Lead serum levels and urinary ALA were about equally effective in providing information. However, these two tests were more sensitive when performed simultaneously than when performed separately. It is suggested that both should be requested when trying to prevent lead poisoning.