Mitochondria-targeted peptides prevent on contrast-induced acute kidney injury in the rats with hypercholesterolemia.

OBJECTIVE: The objective of this study is to evaluate the effect and mechanism of mitochondria-targeted peptides (MTP131 and SPI20) on contrast-induced acute kidney injury (CI-AKI) in rats with hypercholesterolemia. METHOD: Forty SD rats were randomly divided into normal diet group (NN, n = 8) and high cholesterol supplemented dietary group (HN, n = 32). At the end of 8 weeks, the group HN was divided into four subgroups. All Rats were given injection of either diatrizoate (10 mL/kg) or equal volume of normal saline, the rats pretreated with MTP131 or SPI20 were given injection with MTP131 or SPI 20 (3 mg/kg) by peritoneal cavity for 3 times. Blood, urine and renal tissue samples were prepared to determine biochemical parameters. The renal pathological changes were evaluated by hematoxylin and eosin staining and scored semiquantitatively, The protein expression of renal NOX4 was also measured by Western blotting. RESULTS: In diatrizoate-injected rats, Serum creatinine (Scr), fractional excretion of sodium (FeNa%), fractional excretion of potassium (FeK%), pathological scores, renal malondialdehyde (MDA) content, the NADPH oxidase activity and the expression of NOX4 in kidney tissue were significantly increased (p < 0.01). In the groups pretreated with MTP131 or SPI20, the levels of Scr, FeNa%, FeK%, MDA content and NADPH oxidase activity in renal tissue decreased (p < 0.01), the levels of renal super oxygen dehydrogenises and ATPase activity increased (p < 0.01). The renal injuries induced by contrast media (CM) were alleviated. CONCLUSION: MTP131 and SPI20 might protect acute kidney injury induced by CM in rats with hypercholesterolemia.

Ascending tonic-clonic seizure syndrome in a dog following inadvertent intrathecal use of ionic contrast agent.

OBJECTIVE: To describe the successful management of ascending tonic-clonic seizure syndrome in a dog after inadvertent intrathecal administration of ionic contrast material. CASE SUMMARY: A 7-year-old, 5.9 kg, male castrated Miniature Pinscher inadvertently received intrathecal ionic contrast material during a myelogram to investigate cervical pain. Ascending tonic-clonic muscle spasms quickly progressed to generalized seizure activity that was resistant to anticonvulsant medications. The dog developed complete respiratory arrest, which necessitated mechanical ventilatory support for 26 hours. Pneumonia developed and was treated successfully. After resolution of seizure activity and resumption of voluntary respiration, the dog remained tetraparetic for 16 days and was not able to walk on his own for 20 days post contrast injection. Despite a prolonged recovery, the patient survived and recovered normal neurologic function. NEW OR UNIQUE INFORMATION PROVIDED: Intrathecal administration of ionic contrast material resulting in ascending tonic-clonic seizure syndrome is rarely reported in the human and veterinary literature. No previous veterinary report has described successful treatment after prolonged respiratory arrest. In previous veterinary reports, patients recovered complete neurologic function within hours to days in contrast to this report in which the patient was tetraparetic for 16 days. This report demonstrates complete recovery from intrathecal ionic contrast administration is possible despite a high dose of contrast and a prolonged recovery.

Intralesional Ethibloc injections in primary aneurysmal bone cysts: an efficient and safe treatment.

OBJECTIVE: Ethibloc is a fibrogenic and thrombogenic agent recently proposed for the treatment of bone cysts. The purpose of this study is to report the results of direct Ethibloc injection in primary aneurysmal bone cyst (ABC) in children. DESIGN AND PATIENTS: Seventeen patients, aged from 2 to 18 years (mean 8 years), were treated with either a single injection (14 patients) or supplementary injections (3 patients) of Ethibloc. The histological diagnosis was assessed following surgical biopsy and was retrospectively reviewed. The mean follow-up was 5 years (range 18 months to 11 years). RESULTS: At 5 year follow-up, 14 of 17 patients demonstrated complete healing manifest by increased cortical and septal thickening. Surgical excision was required in three patients, in two of whom the ABC increased rapidly in size despite the injection, and in one of whom the healing was incomplete. We observed inflammatory reactions in 16 of 17 patients with local pain and fever. Three patients developed a small cutaneous fistula which resolved spontaneously in a few weeks. No major complications such as deep infection, pulmonary embolism, epiphyseal necrosis or malignant degeneration were observed. CONCLUSION: Percutaneous direct Ethibloc injection is a safe, efficient and noninvasive treatment for ABC. The authors highlight the frequent local reactions.

Peripheral blood eosinophilia associated with gastrointestinal administration of iodinated contrast media.

OBJECTIVE: This study was designed to assess whether gastrointestinal administration of iodinated contrast media results in peripheral blood eosinophilia. MATERIALS AND METHODS: We studied 110 patients in a retrospective review. Diatrizoate meglumine and diatrizoate sodium for abdominal CT were administered to 98 of these patients; 22 of the 98 had also been given the same contrast medium administered by enema. The remaining 12 patients were given diatrizoate sodium for gastrointestinal fluoroscopy. A control group of 65 patients underwent single-contrast barium upper gastrointestinal or enema examinations. WBC and eosinophil counts were determined approximately 24 hr before the examination and every 24 hr thereafter, through the ninth day. RESULTS: Eosinophilia was detected in 17 (15.5%) of 110 patients after gastrointestinal administration of iodinated contrast media. The prevalence of eosinophilia after administration of iodinated contrast media was statistically significantly different compared with that in the control group, in which none of the 65 patients had eosinophilia (p < 0.001). Eosinophilia was detected 48 hr after application of iodinated contrast agents and lasted through the sixth day, with a peak on the fifth day. The prevalence of eosinophilia was independent of route of application, dose, or type of iodinated contrast medium. Eosinophilia in all cases was clinically asymptomatic. CONCLUSION: Eosinophilia that is caused by gastrointestinal administration of iodinated contrast media is a transient, clinically silent phenomenon. It may lead to unnecessary workup for known conditions associated with eosinophilia.

Contrast-induced encephalopathy and seizures in a patient with chronic renal insufficiency.

Radiographic contrast agents are associated with a number of adverse effects, including central nervous system effects and seizures. Almost all contrast agents are primarily filtered and excreted by the kidneys, and they accumulate in patients with end-stage renal disease. Brain retention of contrast associated with high doses is a rare event, having been reported only twice in the literature. We report a case of a 49-year-old male on chronic hemodialysis who developed brain retention of contrast resulting in seizures and encephalopathy after receiving large doses of meglumine/sodium diatrizoate during coronary angiography. He was treated successfully with hemodialysis and suffered no permanent neurologic sequelae. Patients with end-stage renal disease may be at increased risk of adverse effects from contrast when administered in high doses.

Medical malpractice involving radiologic colon examinations: a review of 38 recent cases.

OBJECTIVE: Our purposes were to determine the causes of malpractice claims against radiologists performing contrast examinations of the colon and to design strategies to reduce litigation and diminish patient morbidity. MATERIALS AND METHODS: Reports of malpractice claims were collected from legal journals and databases between 1985 and 1994. For this period, 38 plaintiffs raised 52 allegations of malpractice that involved radiologists performing barium or Hypaque (meglumine diatrizoate; Winthrop Pharmaceuticals, New York, NY) colon examinations. For the 38 cases, 18 plaintiffs for decedents alleged that failure to diagnose colorectal cancer by barium enema examination caused delay in treatment and the patient's death. Eighteen plaintiffs alleged that improper performance of barium (17 cases) or meglumine diatrizoate (one case) colon examinations caused perforation of the colon, resulting in significant morbidity (15 cases) or death (three cases). Miscellaneous causes for malpractice claims were recorded in two cases. RESULTS: In 18 cases of failure to diagnose colorectal cancer, the initial radiographs were interpreted as follows: normal findings in 14 cases, diverticulosis in one case, and spastic bowel in two cases; in the remaining case, colon cancer was missed because of nonopacification of the cecum. In retrospect, 17 of 18 colorectal cancers were visualized. The delay in the diagnosis of colorectal cancer ranged from 5 to 72 months. Missed colorectal cancers occurred in the cecum (two cases), transverse colon (two cases), rectosigmoid area (nine cases), or unspecified area (five cases). In 18 cases of colon perforation, the site was the cecum (one case), transverse colon (one case), extraperitoneal rectum (seven cases), rectosigmoid area (one case), colostomy stoma (two cases), or unspecified area (six cases). One patient experienced anaphylactic shock that required hospitalization. One underwent unnecessary surgery because barium enema films showing colon cancer were mislabeled with her name. CONCLUSION: On the basis of our analyses of malpractice claims, we suggest strategies to prevent medicolegal litigation. Strategies include communicating with the patient about the type and indications of the barium enema examination, performing digital rectal examinations on all patients to detect distal rectal lesions or strictures, recognizing colon perforation, and obtaining immediate surgical consultation if colon perforation occurs. The number of missed colon cancers may be reduced by reading twice or reviewing at a later time all barium enema examinations.

Electrolyte disturbances caused by intravenous contrast media.

The changes in serum electrolytes (sodium, potassium, ionized calcium, and total calcium) produced by high-dose (3 ml/kg) intravenous contrast media were investigated in Japanese white rabbits. The test solutions included sodium/meglumine diatrizoate (370 mgI/ml), sodium/meglumine ioxaglate (320 mgI/ml), iohexol (350 mgI/ml), iopamidol (370 mgI/ml), 20% mannitol, and isotonic saline. The alterations in serum ionized calcium were relatively small and transient, and correlated with changes in the hematocrit. Diatrizoate caused a significant decrease in ionized calcium in comparison with other contrast media and mannitol. The ratio of ionized calcium to total calcium showed no significant decrease in any group. The changes in potassium did not correlate with those in hematocrit. Diatrizoate caused a smaller decrease in potassium than low-osmolality contrast media, which may suggest that diatrizoate caused a shift in potassium from extravascular space to intravascular space. In conclusion, intravenous infusion of high doses of low-osmolality contrast media did not cause clinically significant alterations in serum electrolytes.

[In vivo biochemical aspects of adverse reactions of contrast media--sequential changes of histamine, cyclic AMP, cyclic GMP].

The effect of conventional high-osmolality contrast media (diatrizoate) and new low-osmolality contrast media (iopamidol) on plasma histamine, cyclic AMP and cyclic GMP levels have been examined in a group of 37 mongrel dogs. Plasma histamine levels have a tendency of elevation at five minutes after initiation of injection of diatrizoate and iopamidol in low dose (5 ml/kg). However, statistically no significant changes were found in either diatrizoate or iopamidol in low dose (5 ml/kg) or high dose (15 ml/kg). Plasma cyclic AMP levels have elevated significantly in twenty minutes after termination of injection of iopamidol in low dose (5 ml/kg) and in high dose (15 ml/kg). Also plasma cyclic AMP levels have elevated significantly in twenty minutes after termination of injection of diatrizoate in high dose (15 ml/kg). These findings indicate iopamidol has potential of elevating plasma cyclic AMP as compared with diatrizoate. Plasma cyclic GMP levels have elevated significantly in twenty minutes after termination of injection of diatrizoate in low dose (5 ml/kg) and in high dose (15 ml/kg). Also plasma cyclic GMP levels have elevated significantly in twenty minutes after termination of injection of iopamidol in high dose (15 ml/kg). These findings indicate diatrizoate has potential of elevating plasma cyclic GMP as compared with iopamidol. It is suggested that iopamidol has potential of elevation of plasma cyclic AMP that suppresses histamine release and diatrizoate has potential of elevation of plasma cyclic GMP that enhances histamine release. And so iopamidol is though to be minor histamine releaser than diatrizoate.

High-dose clinical urography with the low-osmolality contrast agent Hexabrix: comparison with a conventional contrast agent.

A double-blind clinical trial was performed in 60 patients to compare Hexabrix (ioxaglate meglumine and ioxaglate sodium) and Renografin-60 (diatrizoate meglumine and diatrizoate sodium). Use of Hexabrix produced higher urinary iodine concentrations, lower urine volumes at 30 minutes, and excretory urograms significantly better in diagnostic quality, as rated by four independent observers. There was no difference in nephrogram quality between contrast agents. Patients receiving Hexabrix had less of an increase in heart rate and demonstrated a slight rise in mean arterial blood pressure, rather than the biphasic rise then fall seen with Renografin-60. There was no significant change for up to 96 hours after urography in results of hematology, clinical chemistry, or urinalysis, except for an increase of 0.005 in urine specific gravity with Renografin-60. Patients reported significantly less body heat, heat in the injection arm, and overall discomfort with Hexabrix. There was a similar amount of nausea and vomiting in the two groups. Hexabrix also caused histaminic-type reactions in three patients.

Renal function following nephroangiography with diatrizoate. Effects of saline, mannitol, and diatrizoate on renal blood flow, glomerular permeability and filtration rate and diuresis in dogs.

The ionic contrast medium diatrizoate used in high-dose unilateral nephroangiography in dogs produced an abnormal nephrogram, 'patchy contrast medium retention', and a marked decrease in renal blood flow in five of eight injected kidneys. Increased glomerular permeability (albuminuria), reduced glomerular filtration rate (creatinine clearance), and reduced osmotic diuresis were demonstrated in all selectively injected kidneys.

The incidence of contrast medium induced acute tubular necrosis following arteriography.

Twenty-one patients slated for high-dose arteriography were studied to investigate the impact of predisposing medical conditions upon contrast medium induced acute renal failure. The study suggests that predisposing medical conditions are the most important factor determining the incidence of acute renal failure and the probability, speed, and degree of recovery of renal function. Patients with diabetes mellitus incur the highest risk of contrast medium induced acute renal failure. A dose relationship is also suggested. Contrast medium doses containing more than 100 g of iodine uniformly produced acute tubular necrosis in patients with predisposing medical conditions. Conversely, contrast medium doses containing less than 80 g of iodine produced clinically manifest acute renal failure in only one of 14 patients with predisposing medical conditions. Subclinical levels of acute renal failure were recognized in a large number of patients by routine measurement of radionuclide filtration fractions, serum creatinine levels, and urine osmolality and sodium concentration.

Iosulamide: a new intravenous cholangiocholecystographic medium.

Iosulamide is a bis-benzoic analogue of metrizoate that shows clear advantages in animal tests over meglumine iodipamide. The intravenous toxicity of iosulamide meglumine is considerably lower than that of iodipamide (Cholografin) in the mouse and rat. The LD50 in mice for iosulamide meglumine is 11,500 +/- 844 mg free acid/kg and for iodipamide is 2380 +/- 290 mg free acid/kg. A threefold difference in toxicity was seen in rats; the LD50 for iosulamide meglumine is 13,600 +/- 1710 mg free acid kg and for iodipamide is 4430 +/- 310 mg free acid/kg. Iosulamide is a highly effective contrast agent for cholangiocholecystographic visualization in cats and monkeys. speed and degree of opacification are equivalent to that of iodipamide at equimolar doses. Studies of biliary and urinary excretion patterns indicate iosulamide is rapidly excreted compared to iodipamide, while at the same time providing equal concentrations in bile on an mg/ml bile basis. A more efficient blood to bile clearance rate and a shorter blood half-life for iosulamide may account for the lower circulating blood levels and rapid total excretion compared to iodipamide. Iosulamide's rapid blood-bile clearance coupled with its extremely low toxicity may allow rapid administration of high doses, affording superior visualization and safety compared to iodipamide. It may also provide visualization of the liver parenchyma with computerized axial tomography, due to the pharmacokinetic profile that provides for high liver clearance but low blood levels. The emetic potential of iosulamide meglumine is quite low compared to iodipamide. Iosulamide meglumine also lacks hypotensive activity. Little or no effect on blood pressure was seen with iosulamide meglumine in cats or monkeys, whereas iodipamide caused marked transient, or sustained, reductions. Iosulamide meglumine did not produce significant toxic effects when administered as single daily intravenous injections to albino rats for three weeks, or in 10-minute intravenous infusions to rhesus monkeys 10 times in 14 days. Clinical trials with iosulamide are under way.

Fetal thyroid hyperplasia, rhesus isoimmunisation, and amniography.

Thyroid hyperplasia was identified at necropsy in 16 of 70 cases of haemolytic disease of the newborn due to rhesus isoimmunisation dying in the years 1959--76. No hyperplasia was found in the thyroids from 140 nonrhesus-affected infants matched for date of birth, bodyweight and length, and gestation, or in cases of haemolytic disease born before 1966. All 16 infants with thyroid hyperplasia had received intrauterine transfusions and the iodine-containing contrast media used for preliminary amniography were the only goitrogenic factors identified. Lipiodol, first used in 1966, was considered to have the greatest effect. The 16 infants with hyperplastic thyroids were less mature and smaller than 22 infants with normal thyroids who had been similarly exposed to contrast media. The high incidence of hyperplasia may be due to immaturity of the adaptive mechanisms which allow most normal individuals to escape the goitrogenic effects of iodine compounds.

High dose urography: incidence and relationship to spontaneous peripelvic extravasation.

A prospective study was undertaken to determine the incidence of spontaneous extravasation of contrast in 82 patients with acute renal colic. The extravasation rate among 37 patients receiving 75 ml of contrast was 8.1%, while the rate among 45 patients receiving either 300 ml of 30% solution by infusion or a 140 ml bolus dose was 24.4%; overall the rate was 17%. Thus the incidence of extravasation was shown to increase with higher doses of contrast media. The primary dose in acute renal colic or other forms of obstructive uropathy should be in the low range (20-25 g 1-); reinjection after screening can be undertaken if necessary.

An approach to the performance of contrast studies in contrast material-reactive persons.

A method of carrying out contrast studies was considered for use in 124 persons with past histories of adverse reactions to contrast media. High-dosage steroid treatment was given before and during the contrast study to 37 patients with previous rash responses and 9 with prior anaphylactoid reactions; only 3 and 1 patients, respectively, of these groups had mild adverse reactions. Patients with past reactions deemed "vasomotor" underwent contrast study without preparative drug therapy without significant adverse effects. Although uncontrolled, this study suggests a possible protective role of steroids in patients with certain previous reactions to contrast media. We do not wish to imply that this is the only approach that can be used in the kind of patients reported here.