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Quantitative SPECT of technetium-99m-DMSA uptake in the kidneys of normal children and in kidneys with vesicoureteral reflux: detection of unilateral kidney disease.

UNLABELLED: Quantitative SPECT was used to evaluate renal functional volume (cc), percent of injected dose/cc (%ID/cc) and renal uptake (%) in 11 children with unilateral vesicoureteral reflux grade 3 or greater, and in 19 normal control children without reflux. METHODS: Studies were performed 4-6 hr after intravenous injection of 0.750-2 mCi of 99mTc-DMSA. RESULTS: Control kidneys (n = 38) had a volume of 99.7 +/- 29.5 cc. The %ID/cc was 0.27 +/- 0.08, and the uptake in one kidney was 24.8% +/- 3.9%. Global renal uptake (right plus left) was 49.6% +/- 7.3%. Functional volume of the control kidneys showed an increase with age, and the %ID/cc showed a steeper decrease with age, resulting in a trend of the kidney uptake to decrease with age. Kidneys with reflux had a decreased kidney uptake of 15.7% +/- 29.5%, compared to age- and sex-matched controls (t = 4.7, p < 0.001). The contralateral kidneys without reflux had a significantly increased total uptake of 33.4% +/- 6.8% as compared to controls (t = 3.44, p < 0.01). Global uptake by the kidneys was 49.2% +/- 8.6% and was not statistically different from controls (t = 1.0, ns). CONCLUSION: Our results suggest that SPECT quantitation of 99mTc-DMSA uptake in each kidney separately could be used as a noninvasive method to assess impairment and compensation of the function of the individual kidney in children with vesicoureteral reflux.

Aging↗

[Clinical evaluation of 99mTc-MAG3 renal imaging: comparison with 99mTc-DTPA, 99mTc-DMSA and 131I-OIH].

The newly developed 99mTc-labeled renal imaging agent, mercaptoacetyltriglycine (MAG3), is a tubular secreted compound. It is expected the most suitable agent to measure renal function and image urinary tract because of the excellent imaging properties and availability of 99mTc and preferred biological qualities of radiohippurates. We examined 15 patients (8 males, 7 females, mean age 55 years old) with renal and urinary tract disease. After drinking 400 ml of water, 185, 370 or 555 MBq of 99mTc-MAG3 was injected with the supine position. Dynamic scans were acquired for 20 minutes on a large field of view gamma camera (ZLC-7500 Siemens Medical Inc.) linked to a computer system (Scintipac-2400 Shimadzu Co.) in a 64 x 64 matrix. Regions of interest (ROI) were placed around each kidney. Curves of 12 seconds frame rate were generated from all two ROIs over the 20 minutes study. The time to peak count (Tmax) and time from peak count to a half count (T1/2) were calculated from the curve data. 99mTc-DTPA renal imaging was examined to the same patients with the same method like 99mTc-MAG3. The renogram of 131I-orthoiodohippurate (OIH) was performed with probe method. The excellent quality of the renal image was obtained with 185-555 MBq of 99mTc-MAG3 compared with the same dose of 99mTc-DTPA respectively. The diagnostic value of 99mTc-MAG3 renal imaging was as well as 99mTc-DMSA renal imaging. The Tmax of 99mTc-MAG3 renogram was same value of that of both 99mTc-DTPA and 131I-OIH renogram. The T1/2 of 99mTc-MAG3 renogram was significantly lower than that of 99mTc-DTPA renogram. The T1/2 of 99mTc-MAG3 renogram was slightly higher that of 131I-OIH renogram. We conclude that the renal imaging of 99mTc-MAG3 was able to acquire the most excellent image and the proper renogram pattern as same as 131I-OIH renogram.

Adult↗

[Technetium 99m labeled dimercaptosuccinic acid (99m Tc-DMSA) scintigraphy in the diagnosis and follow-up of urinary infections in children].

BACKGROUND: The site of a urinary tract infection (UTI) is located by clinical findings plus imaging techniques. Renal imaging with technetium 99mTc-dimercaptosuccinic acid (99mTc-DMSA) has shown promise but its efficacy for detecting acute pyelonephritis is still debated as is its ability to differentiate between acute, potentially curable disease and scarring, definitive changes. PATIENTS AND METHODS: The files of all the 166 patients that underwent one or two (32 patients) 99mTc-DMSA imaging sessions for UTI in 1989 and 1990 in our department were analysed. The results of this technique were compared with the clinical and laboratory data and with those of other imaging techniques (ultrasonography and retrograde voiding cystourethrogram). The patients (92 girls and 74 boys, mean age: 5 years, range 15 days-17 years) were assigned to one of 3 categories: 1) acute pyelonephritis (27 patients), 2) low UTI (60 patients) and 3) uncertain UTI (79 patients), on the basis of the clinical and laboratory data. RESULTS: The first 99mTc-DMSA imaging was normal in 110 children; changes were unilateral in 45 and bilateral in 11 children. Images suggesting either acute or chronic changes were observed respectively in 19 and 48 children. 4 of the 7 acute changes were normalized on the second radioisotope scanning while 2 became worse; 19 of the 23 chronic changes were unchanged at the second scanning. Radioisotope scanning changes were seen in 81% of the patients classified as acute pyelonephritis and in only 27% of those with lower UTI. Reflux was detected in 56% of abnormal kidneys and in 36% of normal kidneys. The results of radioisotope scanning and ultrasound scan findings were not correlated in 24 patients (19 only abnormal radioisotope imaging, 5 only abnormal ultrasound scan). CONCLUSIONS: DMSA scans are useful for investigating and following UTI. They help to distinguish acute pyelonephritis and lower UTI. It is a reliable method of detecting structural abnormalities and identifying children at risk of progressive renal damage.

Adolescent↗

Influence of 2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the renal disposition of mercury in normal and uninephrectomized rats exposed to inorganic mercury.

The effects of the water-soluble chelating agents 2,3-dimercapto-1-propane sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) on the renal disposition of inorganic mercury were studied in normal and uninephrectomized (NPX) rats injected (i.v.) with a nontoxic 0.5-mumol/kg dose of mercuric chloride (HgCl2). When a 100-mg/kg dose of either DMPS or DMSA was injected (i.p.) 24 and 30 hr after treatment with HgCl2, the renal concentration and burden of inorganic mercury decreased markedly in both normal and NPX rats during the 24 hr after the first dose of the respective chelating agent was administered. Treatment with DMPS was more effective than treatment with DMSA in reducing the renal burden of mercury in both groups of rats. The fall in the renal concentration and burden of mercury in both normal and NPX rats was due primarily to a decrease in the content of mercury in the renal cortex and outer stripe of the outer medulla. However, the decrease in the concentration of inorganic mercury in the outer stripe was significantly greater in NPX rats than in normal rats. Both chelating agents caused urinary excretion of mercury to increase significantly in normal and NPX rats. In association with the increased renal release of mercury in NPX rats, the urinary excretion of mercury per gram of kidney was significantly greater in NPX rats than in normal rats. These data indicate that the renal handling of DMPS and DMSA may be altered significantly after a substantial reduction in renal mass. Findings from the present study also show that treatment with DMPS, but not with DMSA, causes the content of mercury in the liver and cellular fraction of blood to decrease in normal and NPX rats. These findings indicate that there are significant differences in the extrarenal handling of these two chelating agents. The findings in the present study suggest that DMPS and DMSA are very effective agents in reducing the renal (and whole body) burden of inorganic mercury in normal and NPX rats.

Animals↗

Trends in the management of childhood lead poisonings.

It is unknown whether prompt medical management (with or without chelation therapy) and environmental intervention have beneficial effects other than stopping the progression towards symptomatic childhood lead poisoning. Stated differently, does prompt intervention have substantive beneficial effects or are untreated lead toxic children with blood lead values between 25-54 micrograms/dl irrevocably damaged by the time of their identification. We are carrying out a prospective treatment outcome study with CaNa2EDTA (when indicated) at our Center to hopefully answer this critical question, within the context of a multidisciplinary study. The results in 162 children indicate that environmental and medical management produce significant reductions in blood lead, erythrocyte protoporphyrin and the lead diuresis during a CaNa2EDTA provocative test. However, CaNa2EDTA treatment failed to decrease bone lead values dramatically, measured by L-line x-ray fluorescence, six months after enrollment in any patient group (treated or untreated with CaNa2EDTA). The uses of L-line x-ray fluorescence in this study and K-line x-ray fluorescence measurements of lead in bone in other reported studies open a wide time window of months to years of lead exposure, compared to 30-45 days, the time of exposure captured by blood lead levels. As with all chelating agents, DMSA should be administered to children in lead free housing, after this drug's toxicity is more widely assessed. The potential capability of DMSA to ameliorate neurobehavioral deficits produced by lead must be systematically assessed and compared with CaNa2EDTA in a randomized, controlled study before the use (s) of either drug become uncritically accepted as the treatment of choice for childhood lead poisoning, in addition to full abatement.

Chelation Therapy↗

Preoperative localization of occult medullary carcinoma of the thyroid gland with single-photon emission tomography dimercaptosuccinic acid.

BACKGROUND: Patients who undergo thyroidectomy for medullary carcinoma of the thyroid gland (MTC) often have elevations of postoperative serum calcitonin levels, which are indicative of metastatic or residual disease. It has been extremely difficult to localize tumor in these patients with standard diagnostic studies such as ultrasonography, computed tomography, or magnetic resonance imaging scans. Previous studies have suggested that planar technetium 99m (V) dimercaptosuccinic acid (DMSA) scintigraphic scans can localize MTC in these patients. We have recently increased the sensitivity of planar scintigraphic images by using single-photon emission tomography (SPECT). This study was performed to compare the sensitivity of planar DMSA scans with that of SPECT DMSA scans. METHODS: Two normal volunteers and three patients with occult MTC after previous total thyroidectomy underwent planar and SPECT DMSA scans. Each patient subsequently underwent surgical exploration based on the DMSA scans. RESULTS: Physiologic DMSA uptake was noted in the nasopharynx, axial skeleton, breast, liver, spleen, heart, kidneys, urinary bladder, great vessels, and skeletal muscles in both normal volunteers and patients with occult MTC. Planar DMSA scans and dynamic computed tomographic scans failed to localize MTC in any of these patients who had minimal disease. SPECT DMSA scans correctly localized cervical MTC in two of three patients, as proved by subsequent surgical resection. One patient who had a negative cervical exploration is presumed to have had a false-positive SPECT DMSA scan. CONCLUSIONS: SPECT DMSA scans appear to be a sensitive, safe, and noninvasive localization technique for patients with occult MTC who have undergone previous thyroidectomy.

Adult↗

The value of performing both IVU and DMSA scan in patients with urinary stone disease.

A study of 60 patients with stone disease was done, all patients had an IVU and DMSA scan. A DMSA scan helps to show clear cortical images, diagnose cortical scars and absence of cortical tissue. While the IVU allows gross evaluation of kidney function and morphological changes, the DMSA scan is an accurate measure of functioning renal mass. Anyhow, both studies are complementary to each other in patients with stones disease.

Adolescent↗

Determination and metabolism of dithiol chelating agents. XV. The meso-2,3-dimercaptosuccinic acid-cysteine (1:2) mixed disulfide, a major urinary metabolite of DMSA in the human, increases the urinary excretion of lead in the rat.

Meso-2,3-dimercaptosuccinic acid (DMSA) in humans is an effective p.o. therapeutically useful chelating agent of Pb. In humans given DMSA p.o., the major urinary metabolite is DMSA-cysteine (1:2) mixed disulfide. In order to determine its efficacy in mobilizing Pb and increasing urinary Pb excretion, the mixed disulfide was given to rats treated previously with Pb acetate. The mixed disulfide was as effective as DMSA in increasing the urinary excretion of Pb and mobilizing Pb from the kidney. DMSA, however, appears to be superior for mobilizing Pb from the liver and the brain. After the mixed disulfide was given s.c. to rats, DMSA was found in the blood and urine. Twenty-four hours after administration, 0.7% of the administered mixed disulfide was found in the urine as DMSA, indicating the mixed disulfide can be reduced to DMSA. The mixed disulfide was also reduced in vitro to DMSA during incubation with rat blood. Although in the rat the DMSA-cysteine (1:2) mixed disulfide mobilized Pb from the kidney, increased the urinary excretion of Pb and was to some extent reduced to DMSA, its fate and pharmacological properties in the human, where it is found after DMSA administration, are unknown.

Animals↗

[Lead poisoning following administration of "home specialties"].

Three cases of lead intoxication after the administration of "house specialties" are illustrated. The lead source could be traced to a lead-containing ointment in all three patients. Two of them suffered lead intoxication as a result of topical application to the lips, while the third had ingested the ointment orally. Clinical signs, diagnosis and therapy of lead poisoning are described in the light of the case reports. The patients were treated with various drugs (N-acetylcysteine and the complex chelators D-penicillamine and 2.3-dimercaptosuccinic acid (2.3-DMSA). The therapeutic effects were determined on specific laboratory features in blood and urine. N-acetylcysteine was not absolutely confirming in our case. D-penicillamine was effective, but only after removal of the source of exposure. Because of its known adverse drug reactions, we preferred the oral lead chelator 2.3-DMSA. Treatment with DMSA resulted in a considerable decrease in the blood lead concentration and in increase in urinary lead output. The urinary excretion of aminolevulinic acid and coproporphyrin normalized under DMSA. The treatment was well tolerated and no appreciable side effects were noticed. The literature on metabolism and the characteristic effects of lead intoxication is reviewed and the production, qualities and administration of emplastrum plumbi are described. All three lead-containing ointments are summarized by the characterizing term "house specialties". One wonders whether it is justified that there is still control and registration of such "house specialties" in Switzerland.

Adult↗

Diagnostic evaluation of thyroid involvement by histiocytosis X.

UNLABELLED: We report the successful diagnosis of thyroid involvement by histiocytosis X due to accurate evaluation of nuclear medicine results. METHODS: A total thyroidectomy specimen from our patient was initially suggestive of medullary thyroid carcinoma. However, histologic reevaluation was performed on the basis of nuclear medicine findings which were incompatible with the original histologic diagnosis. RESULTS: Immunohistochemical and light microscopy studies were performed to obtain the correct diagnosis. Diffuse thyroid involvement by histiocytosis X was demonstrated. CONCLUSION: Thyroid scintigraphy was helpful in successfully diagnosing thyroid involvement by histiocytosis X. Because tracer uptake is related to increased cellularity and metabolism, none of these tracers reported here is specific for defining histiocytosis X.

3-Iodobenzylguanidine↗

[The scintigraphic effect of extracorporeal lithotripsy: prospective series of 25 cases].

25 patients with non complicated renal stones were treated by extracorporeal shockwave lithotripsy (ESWL) using Sonolith 3000 an electrohydraulic generator type. They were evaluated before, 15 days and 3 months after ESWL by renal scintigraphy, using for 15 of them technetium -99m dimer captosuccinic acid and technetium -99m-diethylene-triamine acetate for the last 10. This follow up scintigraphic study shows no reduction of glomerular filtration rate after ESWL but some focal parenchymal lesions. Very few of these lesions persist at 3 months. These parenchymal damages seem to be less frequent and less persistent than with piezo-electric lithotripter.

Adult↗

Superiority of Mi-ADMS to DMSA as parenteral treatment for decreasing mercury (203Hg) body burden in rats.

The efficiency of meso-2,3-dimercaptosuccinic acid (DMSA) and the monoisoamyl ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) in decreasing 203Hg retention was evaluated in rats in relation to age and time of treatment. The experiments were performed on six-week- and seven-day-old Wistar rats, which received 203Hg by intraperitoneal administration. The chelators DMSA or Mi-ADMS were also administered intraperitoneally, twice, on two consecutive days, in doses of 0.25 mmol/kg body weight as early (0.5 and 24 h) or delayed treatment (24 and 48 h, or 48 and 72 h) after 203Hg administration. The retention of 203Hg was determined in the carcass, liver, kidneys and brain six days after administration using gamma scintillation counters (double crystal, well type). In all experimental conditions, regardless of the animals' age and time of chelation therapy, Mi-ADMS was found to be superior to DMSA in reducing the body burden of 203Hg in whole body and organs. Mi-ADMS therefore seems to be a very promising chelator in the treatment of mercury poisoning.

Animals↗

Reversal of gallium arsenide-induced suppression of the antibody response by a mixed disulfide metabolite of meso-2,3-dimercaptosuccinic acid.

Meso-2,3-dimercaptosuccinic acid (DMSA) has been demonstrated to be an effective chelator of lead, mercury and arsenic in humans and in rodent experiments. Studies involving cadmium exposure have typically shown DMSA to be less effective than 2,3-dimercapto-1-propanesulfonic acid, and this is possibly due to an inability of DMSA to cross cell membranes and bind intracellularly-bound metal ions. The present studies were designed to determine whether in vitro addition of DMSA could effectively reverse arsenic-induced immunosuppression in splenocytes exposed in vivo to gallium arsenide (GaAs; 200 mg/kg, intratracheally). In those investigations, DMSA (25-100 microM) was incapable of reversing suppression of the in vitro-generated antibody response induced by in vivo exposure to GaAs. Addition of the recently synthesized 2:1 mixed disulfide (L-cysteine-DMSA) metabolite of DMSA (0.1-100 microM) to cultures of splenocytes exposed in vitro to GaAs (50 microM) dose-dependently reversed GaAs-induced suppression of the antibody-forming cell response with no effect on the vehicle (complete media) response or on cell viability, indicating that the metabolite retained binding capacity. Unlike DMSA, however, addition of the 2:1 mixed disulfide metabolite to splenocyte cultures exposed in vivo to vehicle (0.05% Tween 80 in saline) or GaAs dose-dependently partially reversed GaAs-induced suppression. The reversal of suppression could not be attributed to cleavage of L-cysteine from the 2:1 mixed disulfide metabolite, as addition of equimolar concentrations of L-cysteine or L-cystine (0.2-200 microM) to in vitro generated antibody cultures of splenocytes exposed in vivo to vehicle or GaAs had no effect on the GaAs-induced suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reversal of gallium arsenide-induced suppression of the antibody-forming cell response by vehicle supernatants. I. Pharmacokinetics after in vitro and in vivo exposure.

Exposure of splenocytes in vivo or in vitro to gallium arsenide (GaAs) dose-dependently suppresses the ability of these cells to produce antibody after in vitro immunization with sheep red blood cells. In addition, it has been demonstrated that GaAs exerts immunosuppressive effects early (36 hr) in the generation of a primary antibody-forming cell (AFC) response. The objective of this study was to determine if the GaAs-induced suppression was produced as a result of a GaAs-induced alteration in the secretion of soluble mediators. Supernatants from in vivo and in vitro vehicle (VH)-exposed splenocyte cultures time-dependently reversed GaAs-induced suppression of the in vitro-generated primary AFC response produced by both in vitro (50 microM) and in vivo (200 mg/kg) exposure to GaAs. Supernatants from in vitro GaAs-exposed cells suppressed the VH response 40, 89 and 93% at 24, 36 and 48 hr, respectively. Using the arsenic-binding compound meso-2,3-dimercaptosuccinic acid (100 microM), it was determined that the suppression of the VH response by supernatants from in vitro GaAs-exposed cultures was confounded by the presence of free arsenic in the in vitro GaAs-exposed culture supernatant. In contrast, suppression of in vivo VH-exposed AFC responses by supernatants from in vivo GaAs-exposed cells was not seen. The time-dependent reversal of immunosuppression produced by in vivo or in vitro exposure to GaAs, by supernatants from in vivo and in vitro VH-exposed cells mimics the reported kinetics of suppression by addition of GaAs to antibody cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗