succimer and Chronic-Disease

There is limited information defining the optimal dosing regimen of succimer in the treatment of children with chronic lead poisoning. It is typically administered as a five day course of high dose therapy (1,050 mg/m2/day) followed by 14 days of low dose therapy (700 mg/m2/day). This study compared the effect on blood lead concentrations (BPb) of treatment with this standard regimen and an alternate regimen consisting of two courses of high dose therapy separated by one week. There were significant reductions in the mean BPb in both the standard (n = 7) and alternate (n = 4) treatment groups but there was not a significant difference between the groups. In the standard group, the BPb decreased from 33 +/- 4 to 27 +/- 6 mcg/dL. The BPb decreased from 33 +/- 6 to 23 +/- 4 mcg/dL in those treated with alternate therapy. This study suggests that two short courses of high dose therapy may be an acceptable alternative to standard succimer therapy. Because of the small size of this study, other studies are warranted.

Topics: Chelating Agents; Child; Child, Preschool; Chronic Disease; Drug Administration Schedule; Female; Humans; Infant; Lead; Lead Poisoning, Nervous System, Childhood; Male; Succimer

Chronic arsenic toxicity producing various clinical manifestations is currently epidemic in West Bengal, India, Bangladesh, and other regions of the world. Animal studies have indicated that 2,3-dimercaptosuccinic acid can be used as an oral chelating agent. A prospective, double-blind, randomized controlled trial was carried out to evaluate the efficacy and safety of 2,3-dimercaptosuccinic acid for chronic arsenicosis due to drinking arsenic-contaminated (> or = 50 micrograms/L) subsoil water in West Bengal.. Twenty-one consecutive patients with chronic arsenicosis were individually randomized (random number; assignment made by individual not evaluating patients) into 2 groups: 11 patients (10 male, age 25.5 +/- 8 years) received 2,3-dimercaptosuccinic acid 1400 mg/d (1000 mg/m2) in the first week and 1050 mg/d (750 mg/m2) during the next 2 weeks with a repeat course 3 weeks later. The other 10 patients (all male, age 32.2 +/- 9.7 years) were given placebo capsules for the same schedule. The clinical features were evaluated by an objective scoring system before and after treatment. Routine investigations including liver function tests, arsenic concentrations in urine, hair, and nails, and skin biopsy evaluations were also completed.. Though there was improvement in the clinical score of 2,3-dimercaptosuccinic acid-treated patients, similar improvement was observed in the placebo-treated group. There were no statistical differences in the clinical scores between the 2 groups at the beginning and at the end of treatment. Similarly, no differences were found for the other investigated parameters.. Under the conditions of this study, 2,3-dimercaptosuccinic acid was not effective in producing any clinical or biochemical benefit or any histopathological improvement of skin lesions in patients with chronic arsenicosis.

Topics: Adolescent; Adult; Antidotes; Arsenic; Chronic Disease; Double-Blind Method; Humans; India; Liver Function Tests; Male; Poisoning; Prospective Studies; Skin; Succimer; Water Pollutants, Chemical

The renal radiopharmaceutical preparations 99mTc-DMS and 99mTc-GH were examined chemically, biologically and clinically. Both preparations are of high radiochemical purity. The biodistribution of both preparations was examined in experimental animals at different time intervals, from 15 min to 4 hr; the precentage of incorporation of 99mTc-DMS into kindeys is much higher (29.4% to 52.0%) than that of 99mTc-GH (12.80% to 22.20%). Both preparations accumulate to a greater extent in the renal cortex than in the medulla. The most suitable time for renal scintigraphy for 99mTc-DMS is 90--150 min while for 99mTc-GH it is 60--90 min. It is concluded that 99mTc-DMS is more suitable for static scintigrams on the scanner and 99mTc-GH for dynamic studies with the gamma camera.

Topics: Animals; Chronic Disease; Clinical Trials as Topic; Heptoses; Humans; Kidney; Liver; Male; Polycystic Kidney Diseases; Pyelonephritis; Radiochemistry; Radionuclide Imaging; Rats; Succimer; Sugar Acids; Sulfhydryl Compounds; Technetium; Time Factors; Tissue Distribution

Monoisoamyl DMSA (MiADMSA), a lipophilic chelating agent has emerged as a promising drug for the treatment of arsenic. The present study aimed at exploring the optimum dose and route of administration for achieving maximum arsenic elimination with minimal side effects. We also carried out a pharmacokinetic analysis of this drug to support arsenic chelation. Rats were exposed to arsenic (25 ppm) for 6 months and later received MiADMSA (50 or 100 mg/kg) orally and via i.p. route for 5 days. Oxidative stress parameters and arsenic levels in soft tissues, liver function test and histopathology of liver and kidney were performed. Plasma kinetic of MiADMSA (plasma-free drug and total drug) at 50 and 100 mg/kg p.o. was carried out. Arsenic exposure resulted in significant oxidative stress and hepatotoxicity. MiADMSA at 50 mg/kg dose administered orally provided about 45% and 75% protection against oxidative stress and in lowering body arsenic burden, respectively, against 25% and 40% via i.p. route. Pharmacokinetic analysis supported prolonged availability of the drug through oral administration. Collectively, these findings led us to conclude that oral administration of MiADMSA was more effective than intraperitoneal administration and that the minimum effective dose with least side effects was 50 mg/kg.

Topics: Administration, Oral; Animals; Arsenic; Arsenic Poisoning; Chelating Agents; Chronic Disease; Copper; Dose-Response Relationship, Drug; Glutathione; Glutathione Disulfide; Kidney; Liver; Liver Function Tests; Male; Oxidative Stress; Rats; Rats, Wistar; Succimer; Zinc

We report a case of total hyperpigmentation of the skin, severe itching, muscle weakness and thrombocytosis. Laboratory investigation showed white blood cell (WBC) 8.2 x 10(6)/L, Hb 125 g/L, platelets 1221 x 10(6)/L and urinary lead after DMSA mobilization test 2684 mcg/g creatinine (normal <5). Chelation therapy with DMSA resulted in complete recovery of the hyperpigmentation, itching and thrombocytosis. Lead poisoning should be considered in the differential diagnosis of obscured thrombocytosis.

Topics: Chelating Agents; Chelation Therapy; Chronic Disease; Coloring Agents; Humans; Lead Poisoning; Male; Middle Aged; Succimer; Thrombocytosis

This report presents case profiles of three siblings in a family of lead (Pb) glazing workers living in a Pb-contaminated Andean village who presented with extreme plumbism (blood Pb levels: 47 to 128 microg/dl) from childhood to adolescence. These cases are examples of persons who have chronic Pb poisoning as a result of prolonged occupational and environmental exposure in a Pb-glazing ceramic cottage industry in the study area. Using behavioral and physiological techniques for measuring the integrity of the peripheral and central auditory systems, including otoacoustic emissions, and replicated auditory brainstem electrophysiological potentials, the authors found normal auditory neurosensory function in each patient, thus ruling out hearing impairment as a basis for adverse neurocognitive outcomes. This finding is contrary to the prevailing view regarding the detrimental effects of Pb poisoning on the cochlear and auditory brainstem of children. Performance on tests of visual spatial intelligence and auditory memory/attention was below average in these patients, which may underlie their reported learning disabilities. In two of the cases, there was an improvement in cognitive performance following a lowering of PbB levels from chelation therapy and Pb prevention education, suggesting some level of reversibility of their neurocognitive deficits. Nevertheless, these case profiles suggest that if the patients persist in Pb-glazing activities, in spite of repeated chelation therapy and family counseling, they may continue to be re-intoxicated and remain at risk for learning disabilities and other neurological impairments.

Topics: Adolescent; Ceramics; Chelation Therapy; Child; Chronic Disease; Ecuador; Environmental Pollutants; Female; Hearing; Humans; Lead Poisoning, Nervous System, Childhood; Male; Succimer

Co-administration of iron in combination with monoisoamyl dimercaptosuccinic acid (MiADMSA) against chronic arsenic poisoning in mice was studied. Mice preexposed to arsenic (25 ppm in drinking water for 6 months) mice were treated with MiADMSA (50 mg/kg, intraperitoneally) either alone or in combination with iron (75 or 150 mg/kg, orally) once daily for 5 days. Arsenic exposure led to a significant depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity, hematocrit, and white blood cell (WBC) counts accompanied by small decline in blood hemoglobin level. Hepatic reduced glutathione (GSH) level, catalase and superoxide dismutase (SOD) activities showed a significant decrease while, oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS) levels increased on arsenic exposure, indicating arsenic-induced hepatic oxidative stress. Liver aspartate and alanine transaminases (AST and ALT) activities also decreased significantly on arsenic exposure. Kidney GSH, GSSG, catalase level and SOD activities remained unchanged, while, TBARS level increased significantly following arsenic exposure. Brain GSH, glutathione peroxidase (GPx), and SOD activities decreased, accompanied by a significant elevation of TBARS level after chronic arsenic exposure. Treatment with MiADMSA was marginally effective in reducing ALAD activity, while administration of iron was ineffective when given alone. Iron when co-administered with MiADMSA restored blood ALAD activity. Administration of iron alone had no beneficial effects on hepatic oxidative stress, while in combination with MiADMSA it produced significant decline in hepatic TBARS level compared to the individual effect of MiADMSA. Renal biochemical variables were insensitive to any of the treatments. Combined administration of iron with MiADMSA also had no additional beneficial effect over the individual protective effect of MiADMSA on brain oxidative stress. Interestingly, combined administration of iron with MiADMSA provided more pronounced depletion of blood arsenic, while no additional beneficial effects on tissue arsenic level over the individual effect of MiADMSA were noted. The results lead us to conclude that iron supplementation during chelation has some beneficial effects particularly on heme synthesis pathway and blood arsenic concentration.

Topics: Animals; Arsenic; Arsenic Poisoning; Brain; Chronic Disease; Drug Therapy, Combination; Iron; Kidney; Liver; Male; Mice; Oxidative Stress; Succimer; Zinc

We report the case of an 81-year-old woman in whom clinical signs and features of electromyographic activity patterns were consistent with amyotrophic lateral sclerosis (ALS). Increased blood level and massive urinary excretion of mercury proved mercury intoxication. Despite a chelation treatment with Meso 2-3 dimercaptosuccininc acid (DMSA), she died after 17 months. The pathophysiology of sporadic ALS remains unclear. However, the role of environmental factors has been suggested. Among some environmental factors, exposure to heavy metals has been considered and ALS cases consecutive to occupational intoxication and accidental injection of mercury have been reported. Although no autopsy was performed, we discuss the role of mercury intoxication in the occurrence of ALS in our case, considering the results of experimental studies on the toxicity of mercury for motor neuron.

Topics: Activities of Daily Living; Aged, 80 and over; Chelating Agents; Chronic Disease; Disease Progression; Fatal Outcome; Female; Humans; Mercury; Mercury Poisoning; Motor Neuron Disease; Motor Neurons; Neurologic Examination; Succimer

To determine whether untreated asymptomatic bacteriuria is associated with renal scarring in children with neuropathic bladders managed with clean intermittent catheterization (CIC).. Retrospective study of 207 patients aged 1 to 30 years (mean 11.9 +/- 5.5 years) treated with CIC for a mean duration of 6.6 +/- 3.9 years by the spina bifida program at Children's National Medical Center. All patients were examined for renal scarring with dimercaptosuccinic acid (DMSA) renal scans. Catheterized urine cultures were obtained annually, but bacteriuria ( > 10,000 colony-forming units of a single organism per milliliter) was treated only if the patients had symptoms or if vesicoureteral reflux (VUR) was present.. Of 207 children, 176 (85%) had one or more episodes of untreated asymptomatic bacteriuria and 72 (35%) had one or more febrile episodes associated with positive urine culture results. Biannual DMSA scans detected 54 new scarring episodes in 42 patients. Of newly recognized scars, 55% were preceded within 1 year by a febrile infection, 26% were detected in patients with VUR and asymptomatic bacteriuria, and 19% were detected in new patients during their initial examination. Univariate analysis revealed that new scarring was present in 35 of 176 patients with asymptomatic bacteriuria compared with 7 of 31 patients without (p = 809). Logistic regression analysis revealed that factors associated with scarring were febrile infections (adjusted odds ratio [OR] = 30.6, 95% confidence interval [CI] = 9.8 to 95.8), age more than 20 years (OR = 4.3, CI = 1.01 to 18.5), the presence of bladder trabeculation (OR = 2.7, CI = 1.0 to 7.6), and VUR (OR = 58.8, CI = 6.3 to 547.3), but asymptomatic bacteriuria was not associated with scarring.. In the absence of VUR, asymptomatic bacteriuria in patients undergoing CIC is not a significant risk factor for scarring and does not require antibiotic therapy.

Topics: Adult; Bacteriuria; Child; Child, Preschool; Chronic Disease; Cicatrix; Female; Humans; Infant; Kidney; Kidney Diseases; Logistic Models; Male; Organotechnetium Compounds; Radionuclide Imaging; Retrospective Studies; Risk Factors; Self Care; Spinal Dysraphism; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Catheterization

The therapeutic efficacy of two thiol chelators, meso 2,3-dimercaptosuccinic acid (DMSA) or 2,3-dimercaptopropane sulfonate (DMPS) in treating chronic arsenic intoxication was investigated in male rats. Both the chelators were effective in promoting urinary arsenic excretion and restoring arsenic induced inhibition of blood delta-aminolevulinic acid dehydratase activity and hepatic glutathione level. Elevation of urinary delta-aminolevulinic acid excretion and arsenic concentration in blood, liver and kidneys were reduced significantly by both the chelators. Histopathological lesions induced by arsenic were also effectively reduced by the above chelators. DMSA being more effective than DMPS. The results suggest DMSA and DMPS to be effective antidotes for treating chronic arsenic toxicity in experimental animals.

Topics: Animals; Arsenic Poisoning; Chronic Disease; Kidney Tubules; Liver; Male; Poisoning; Rats; Succimer; Unithiol

A set of criteria was developed to standardize assessment of DMSA renal scintigraphy which were performed to evaluate children for acute pyelonephritis and renal scarring. This study was undertaken to assess intra- and interobserver variability in the interpretation of DMSA renal scintigraphy using these criteria. Renal contours and parenchyma were assessed in three zones. Contours were assessed as normal or abnormal and parenchymal defects were evaluated in terms of character, shape and degree in three regions (upper and lower pole and midzone). Two nuclear medicine physicians blindly reviewed 57 DMSA scintigraphy on two occasions each. Disagreement of each observer's evaluation of the same scintigraphy on two different occasions was described as intraobserver variability, and the comparison between readings by each of the two observers was described as interobserver variability. High levels of intra- (95.9% and 90.6% respectively, p < 0.05) and interobserver agreement (84.4%, p < 0.05) were demonstrated. There were minor differences in inconsistencies between the two kidneys or different kidney zones. We conclude that standardization of criteria resulted in higher intra- and interobserver consistency in interpretation of DMSA scintigraphy.

Topics: Acute Disease; Adolescent; Child; Child, Preschool; Chronic Disease; Cicatrix; Humans; Infant; Kidney; Observer Variation; Organotechnetium Compounds; Pyelonephritis; Radionuclide Imaging; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid

Topics: Chronic Disease; Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

A 54-year-old male with chronic lead poisoning was treated with 2.3-dimercaptosuccinic acid (DMSA). A daily dosage of 30 mg/kg body weight for three days and 20 mg/kg for four days resulted in a decrease of the blood-lead concentration (B-Pb) from 3.7 to 0.7 mumol/l; the total amount of lead excreted in the urine during the first seven 24 hr periods was 75 mumol. After the treatment, B-Pb slowly increased to 3.3 mumol/l. A second treatment was then initiated and resulted in similar changes in B-Pb. However, during the third treatment, the patient developed a mucocutaneous vesicular flare; the eruptions faded after cessation of the chelation therapy, but could be provoked by DMSA doses of 10 mg/kg and above. Despite the small number of treatment courses, the patient showed obvious mental improvement and reported less headache and improved memory. Thus, DMSA is an efficient chelator that results in a rapid, though temporary decrease in B-Pb. Although oral treatment with this chelator may be supervised from the out-patient clinic, careful monitoring for potential side effects is recommended.

Topics: Chelation Therapy; Chronic Disease; Humans; Lead Poisoning; Male; Middle Aged; Occupational Diseases; Succimer

Twelve Yucatan micropigs (3 controls; 3 sham-operated; 6 with unilateral obstruction) were studied to assess the value of noncontrast and contrast-enhanced (Gadolinium-DTPA) magnetic resonance (MR) imaging in the evaluation of partial ureteral obstruction. MR findings were correlated with findings of quantitative (Tc-99m-DMSA) scintigraphy, and histology. On noncontrast T1-weighted images, the normal porcine kidney demonstrated good corticomedullary contrast (CMC = 16.8% +/- 5.0). Five minutes after administration of Gd-DTPA, there was enhancement of the renal cortex (+24.4% and medulla (+46.2%), and CMC was no longer discernible. Enhancement of the urine within the collecting system (+119.1%) was also observed. The obstructed kidneys demonstrated marked thinning of the renal parenchyma and decreased signal intensity on noncontrast T1- and T2-weighted images (P less than 0.01). Urine in the dilated collecting system did not differ significantly from urine in controls except in the three animals with urinary tract infection (P less than 0.05). Five minutes following injection of Gd-DTPA, there was enhancement of the renal parenchyma in all kidneys. Excretion was seen in three pigs and no excretion in two. Thus, useful information can be obtained in partial ureteral obstruction from both pre-contrast and Gd-DTPA-enhanced MR images of the kidney.

Topics: Animals; Chronic Disease; Contrast Media; Gadolinium DTPA; Kidney; Kidney Cortex; Kidney Medulla; Kidney Pelvis; Magnetic Resonance Imaging; Organometallic Compounds; Pentetic Acid; Radionuclide Imaging; Succimer; Swine; Swine, Miniature; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Ureteral Obstruction

A method of high frequency image filtration improving the quality of imaging, and more precise renometry with measurement of the total count and the level of RP kidney accumulation were used for raising the informative value of the results of renal scintigraphy with 99m Tc-DMSA. 54 patients with unilateral pyelonephritis, 46--with bilateral pyelonephritis, 15--with nephroptosis, and 10 healthy persons were examined. Informative values were calculated on the basis of the results of these investigations. The sensitivity of routine renometry was 0.88, its specificity--0.27 and precision--0.78; the same indices for routine static scintigraphy were 0.88; 0.4 and 0.84; for modified renal investigations--0.98; 0.77 and 0.96, respectively. The results of the investigations have shown that the use of scintigraphy with improved quality of kidney images in parallel with modified renometry raises the informative value of renal studies with 99m Tc-DMSA and precision of diagnosis of renal parenchymal lesions.

Topics: Algorithms; Chronic Disease; Diagnosis, Computer-Assisted; Filtration; Humans; Image Enhancement; Kidney; Kidney Diseases; Organometallic Compounds; Prolapse; Pyelonephritis; Radionuclide Imaging; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid

Radioisotopic renal imaging proved to be much more sensitive than excretory urography in diagnosing renal parenchymal damage in 6 children with acute febrile urinary tract infections. This increased sensitivity may affect clinical management. More importantly, it may change the interpretation of scientific studies evaluating the natural history and treatment of vesicoureteral reflux.

Topics: Child; Child, Preschool; Chronic Disease; Female; Humans; Infant; Kidney; Male; Pyelonephritis; Radionuclide Imaging; Succimer; Sulfhydryl Compounds; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid; Urography; Vesico-Ureteral Reflux

Topics: Chronic Disease; Humans; Lead Poisoning; Male; Middle Aged; Succimer; Sulfhydryl Compounds; Wine

Partial functions of the kidney, i.e. renal blood flow, GFR etc, can be estimated with radionuclide techniques as safe and non-invasive methods. Many methods have been published to distinguish between obstructive and non-obstructive hydronephrosis. A simple and highly relevant technique is the diuretic radionuclide urography which should be done in all patients with questionable urographic or sonographic findings. The evaluation of split renal function is somewhat difficult because tissue absorption will influence uptake determination. In hydronephrosis this absorption cannot be predicted by sonographic measurement of the kidney's depth and mass. A solutions is to calculate the absorption in these patients by stepwise scintigraphy. Continuous quality control of the technique is emphasized.

Topics: Adult; Child; Chronic Disease; Humans; Hydronephrosis; Infant; Iodohippuric Acid; Kidney Function Tests; Radioisotope Renography; Succimer; Technetium; Technetium Tc 99m Dimercaptosuccinic Acid