A double-blind clinical trial of iopamidol versus metrizamide for lumbosacral myelography

A double-blind study was performed to compare metrizamide with the new iodinated water-soluble nonionic contrast medium, iopamidol, for conventional and computerized tomography lumbosacral myelography. Both contrast agents were used in 30 patients, and were equivalent in terms of image quality and clinical accuracy. Headaches and nausea were less severe using iopamidol. The most striking difference was found in adverse neurobehavioral reactions and associated electroencephalographic abnormalities, which were noted in 17% of the metrizamide group but were not seen with the use of iopamidol. Iopamidol appears to be superior to metrizamide for intrathecal applications. An explanation of the differential neurotoxicity is provided.     

Effect of injections of contrast media on regional uptake of (14C)-2-deoxyglucose by the rat brain

Mechanisms contributing to the rare but consistent neurotoxicity of contrast media currently in clinical use for the radiological examination of the subarachnoid space remain to be isolated. We assessed, by means of the (¹⁴C)-2-deoxy-D-glucose (2-DG) autoradiographic method, the effect of three non-ionic, low-osmolar contrast media, namely metrizamide, iopamidol and iohexol, on the local cerebral glucose utilization in the rat brain after intracisternal application.

A significant (- 30%) global reduction of the brain's metabolic activity occurred following intracisternal metrizamide injection. When compared with the mock-CSF control group the greater relative changes were observed in the supratentorial grey matter structures. In contrast, no significant changes were observed in metabolic brain activity in rats treated intracisternally with iopamidol and iohexol.

These findings were consistent with the hypothesis that metrizamide is a competitive inhibitor of human brain hexokinase. The apparent lack of interference on neural tissue metabolism makes the second generation contrast media less neurotoxic and more suitable for neuroradiological subarachnoid investigations in clinical settings. The present experimental work establishes the 2-DG method as a viable laboratory approach to investigate aspects of neuronal dysfunction induced by contrast media.     

Serum concentration of iopamidol after retrograde urethrography in male patients with outlet obstructive symptoms

Serum concentration of iopamidol was measured in 29 male patients with outlet obstructive symptoms after retrograde urethrography. Although no patient showed extravasation, serum iopamidol level was detectable in 4 (14%) patients. Since severe adverse effects are considerably reduced with iopamidol, we prefer to use this contrast medium for retrograde urethrography in male patients with outlet obstructive symptoms.     

Iohexol versus metrizamide for lumbar myelography: preliminary report of double-blind trial

Lumbar myelography was performed in 38 patients; 19 received iohexol (an investigational aqueous contrast agent) and 19 received metrizamide. Iohexol is stable in solution, which is not the case with metrizamide. There was no other significant difference in diagnostic utility or quality between the two media. However, there was considerable postmyelography morbidity in the metrizamide group, but no postmyelography morbidity in the iohexol group. Preliminary clinical evidence suggests that iohexol is significantly superior to metrizamide as a contrast agent for lumbar myelography.     

Iopamidol myelography: morbidity in patients with previous intolerance to iodine derivatives

The records of 1005 patients who underwent iopamidol myelography between January and September, 1988, were reviewed. In this group, 50 patients had histories suggestive of untoward sequelae associated with iodine intake, contact, or administration. The charts of these patients were carefully reviewed, and none of them had any reactions or sequelae suggestive of toxicity or an allergic response after iopamidol myelography. It is concluded that, even in patients with a previous history suggestive of intolerance to iodine administration, iopamidol myelography is generally a safe procedure.     

低渗非离子造影剂对肾小管上皮细胞凋亡的作用及其机制

目的 探讨低渗非离子型造影剂碘必乐诱导体外培养的人肾小管上皮细胞（HK-2细胞）凋亡的作用及机制。 方法 体外培养的HK-2细胞,分为阴性对照组、不同剂量（1.16、4.63、18.5、74、296 gI/L）的碘必乐作用组（作用时间为6 h）。通过流式细胞仪、Hoechst 33258染色观察细胞凋亡的比例和形态学变化;Western印迹方法检测凋亡蛋白天冬氨酸半胱氨酸蛋白酶3（caspase-3）的表达水平,并选取作用最强的剂量（296 gI/L）刺激2、4、6、12 h,观察caspase-3表达变化。选取不同剂量碘必乐作用1 h,与阴性对照组比较,观察细胞外信号调节激酶（ERK）和p38丝裂原活化蛋白激酶（MAPK）信号通路磷酸化水平的变化,并观察不同剂量p38MAPK抑制剂SB203580对碘必乐诱导的caspase-3和Bcl-2表达的影响。 结果 流式细胞仪检测结果示74、296 gI/L碘必乐作用下细胞凋亡率较阴性对照显著升高（均P < 0.05）。Hoechst 33258染色结果示296 gI/L碘必乐可致明显的细胞凋亡形态学改变,凋亡细胞核呈致密浓染或核碎裂。Western印迹检测方法表明,碘必乐以剂量和时间依赖方式诱导细胞内caspase-3表达,以296 gI/L作用12 h表达最强;各剂量碘必乐作用下细胞内ERK1/2磷酸化水平与阴性对照组的差异均无统计学意义（均P > 0.05）,而一定剂量的碘必乐处理组细胞内p38MAPK磷酸化水平较阴性对照组显著升高（均P < 0.05）。应用p38MAPK特异性抑制剂（30 μmol/L）预处理2 h可以阻断细胞内p38MAPK信号通路的磷酸化,抑制碘必乐诱导的细胞内caspase-3表达并部分上调Bcl-2表达,与碘必乐阳性对照组的差异均有统计学意义（P < 0.05）。 结论 低渗非离子型造影剂碘必乐以剂量和时间依赖方式诱导体外培养的HK-2细胞凋亡,其机制可能与上调caspase-3和下调抗凋亡蛋白Bcl-2有关,而p38MAPK信号通路的激活可能参与了该过程的调控。     

The diagnostic method of localization of cerebrospinal fluid rhinorrhea by digital video subtraction system

Demonstration of the exact site of the dural fistula in cerebrospinal fluid rhinorrhea is difficult. Previous reports present the methods of metrizamide cisternography combined with both hypocycloid tomography and computed tomography. But in these methods, direct, dynamic, actual and real-time visualization of the fistula with minimal dose of metrizamide is rather difficult. By using digital video subtraction system (Philips DVI-2CV), we could visualize the direct, dynamic and actual site of fistula with small amount of metrizamide instilled into the suboccipital subarachnoid space with the patient prone position. We report a successful case of traumatic cerebrospinal fluid rhinorrhea drained through the bony defect at the planum sphenoid into the posterior ethmoid sinus. This is the first report to deal with the usefulness of digital video subtraction system for exact localization of cerebrospinal fluid rhinorrhea. We emphasize the usefulness of metrizamide cisternography by the digital video subtraction system combined with the metrizamide computed tomographic cisternography for the precise localization of dural fistula.     

Localization of dural fistulas using metrizamide digital subtraction fluoroscopic cisternography

Demonstration of the exact site of dural fistulas in cases of cerebrospinal fluid rhinorrhea is difficult. Previous reports have described the use of metrizamide cisternography combined with either hypocycloidal tomography or computerized tomography; however, direct, dynamic, real-time visualization of the fistula is difficult with instillation of a minimal dose of metrizamide using those methods. A digital video subtraction fluoroscopy system can visualize the actual site of the fistula directly and dynamically using only a small amount of metrizamide.     

Complications of myelography after partial metrizamide withdrawal

Lumbar metrizamide myelography (LMM) has been associated with a high incidence of side effects. A total of 94 patients underwent LMM for suspected disc disease or spinal stenosis. In Group 1 a 22-gauge spinal needle was used. Containing the same amount and concentration of metrizamide, an 18-gauge spinal needle was used in Group 2 after which there was partial withdrawal of the metrizamide (average withdrawal: 73%). In Group 1 a total of 38% of patients experienced one side effect whereas 8.5% had two side effects. In Group 2 a total of 8.5% of patients experienced one side effect and 4.25% had two side effects. This study demonstrates a statistically (P less than 0.003) lower incidence of side effects with metrizamide withdrawal after myelography.     

Comparison between a low-osmolar ionic (ioxaglate) and a low-osmolar non-ionic (iopamidol) contrast agent in cardiac imaging

The aim of this study was to compare the subjective, haemodynamic and electrocardiographic changes associated with a low-osmolar ionic (ioxaglate) and a low-osmolar non-ionic (iopamidol) injection during routine ventriculography and coronary angiography. The double-blind study was terminated when 120 patients had been randomised to either ioxaglate or iopamidol. More patients (9) experienced nausea with ioxaglate than with iopamidol (2). One patient in each group developed urticaria during and immediately after the procedure. No patient in any group developed serious arrhythmias during dye injection. After left ventriculography the mean left ventricular end-diastolic pressure (LVEDP) increased significantly in the iopamidol group (P less than 0.001). The difference in the rise of LVEDP in the two groups was not significant. In both groups the systolic arterial pressure fell transiently after left ventriculography (P less than 0.001). The difference in the mean fall of the pressure was not significant. There was no significant change in heart rate with either left ventricular or selective right and left coronary artery injections in any of the groups. In the ioxaglate group with both right and left coronary artery injection, the mean QRS duration, mean Q-T interval and T-wave amplitude changed significantly (P less than 0.001). In the iopamidol group the QRS duration and Q-T interval were prolonged significantly only with left coronary artery injection (P less than 0.001). In all parameters no significant differences were noted in the two groups; only minor differences in the effects caused by the two contrast agents could be demonstrated.     

Advantages of ambulatory metrizamide myelography with contrast CT tomography

Outpatient metrizamide cervical and lumbar myelography complimented by CT scanning is a safe and effective method of assessing the contents of the neural canal. By minimizing the dose of metrizamide and using a small needle, the incidence of side effects is reduced. The techniques of needle insertion metrizamide injection and radiography as well as pre- and post procedure care are described in detail.     

Interstitial CT lymphography-guided localization of breast sentinel lymph node: preliminary results

BACKGROUND: Accurate localization of the breast sentinel lymph node (SLN) can be challenging as a minimally invasive approach to the treatment of early-stage breast cancer. We tested the potential capability of interstitial computed tomographic lymphography (CT-LG) using a conventional contrast agent (iopamidol) for SLN mapping. METHODS: In 14 female dogs, 0.5 and 1 mL of undiluted iopamidol was injected subcutaneously into the 2 skin areas overlying the mammary gland. Contiguous, 2 mm-thick multidetector helical CT images were obtained through the upper breast and axilla before, and for 60 minutes after, gentle massage at the injection site. Three-dimensional (3D) CT images were obtained from the postcontrast images showing the greatest SLN enhancement. This CT-LG with 2 mL of iopamidol was also evaluated in 5 human female volunteers. RESULTS: The direct connection of SLN and lymphatic vessels draining from the injection sites in the animal models was clearly visualized, even with 0.5 mL of iopamidol. With this dose, the SLN attenuation was maximally enhanced, with a mean of 274 Hounsfield units (HU) on the first postcontrast images. The topographic 3D images provided the comprehensive anatomy of these lymphatic pathways. Of the 28 SLNs and 184 distant nodes visualized on CT images, all of the SLNs (100%) and 161 (87.5%) of the distant nodes could be resected at premortem and/or postmortem, with a good correlation in the locations and sizes with those on the CT images. The CT-LG effectively localized 5 SLNs with averaged maximum attenuation of 223 HU in the human volunteers, without any significant adverse effects. CONCLUSION: Interstitial CT-LG using small volumes of iopamidol can sufficiently visualize breast lymphatic drainage and may have potential utility for breast SLN mapping.     

Cerebrospinal fluid dynamics in traumatic intracerebral pneumocephalus evaluated with computed tomographic cisternography

Cerebrospinal fluid dynamics in a case of traumatic intracerebral pneumocephalus are evaluated with metrizamide computed tomographic cisternography. Accumulation of metrizamide into the air cyst through the ventricular system is due to transependymal penetration, which can be explained by the mechanism of the pressure gradient from the ventricle towards the air cyst.     

The Epileptogenicity of Neurolept Anaesthesia in Patients During and After Neuroradiological Examinations with Metrizamide

Previous experimental studies caution against the use of neurolept anaesthesia during subarachnoid injection of metrizamide for neuroradiodiagnostic procedures because of severe epileptogenic complications. To examine whether these recommendations are relevant in the clinical situation or not, 104 patients were studied. They underwent neuroradiological investigations with metrizamide subarachnoidally and were anaesthetized with neurolept anaesthesia either during the investigation (59 patients, Group I) or within 48 h afterwards (45 patients, Group II) when a neurosurgical operation was performed. In 10 patients of Group I, EEG was recorded during the investigation. All patients were observed for occurrence of clinical epileptic manifestations during and after the anaesthesia. Apart from one patient who had a short episode of suspected epileptogenic EEG-activity shortly after the injection of metrizamide, none of the other patients showed EEG-abnormalities of epileptogenic type and none of them had any clinical signs of epileptic manifestations. On the basis of the results of this clinical study it is concluded that neurolept anaesthesia does not increase the risk of epileptic complications during neuroradiological investigations with metrizamide.     

Comparison of toxicity of radiocontrast agents to renal tubule cells in vitro

We have previously reported that radiocontrast agents induce direct renal tubule cell toxicity in vitro. The observed toxic effects were markedly potentiated by concomitant hypoxia. In addition, we have reported that the ionic radiocontrast agent diatrizoic acid is more toxic than the nonionic radiocontrast agent iopamidol in this system. Using suspensions enriched in rabbit renal proximal tubule segments, we compared the direct toxicities of the ionic dimeric ioxaglic acid to the nonionic monomeric compound iopamidol. Toxicity was assessed by comparing tubule potassium and calcium content, ATP levels, and respiratory rates after exposure to clinically achievable concentrations of radiocontrast agents. Ioxaglate (25 mM) produced significant declines in tubule cation content and respiratory rate with 30 min of hypoxia followed by 60 min of reoxygenation compared to molar-equivalent concentrations of iopamidol under similar conditions. Meglumine, a cationic compound frequently present in ionic contrast agent solutions, and ioxaglate tubule toxicity was additive. Iopamidol and ioxaglate exhibited similar tubule cell toxicity when comparison was based on iodine content. These experimental results suggest that the intrinsic nephrotoxic potential of ioxaglic acid is greater than that of iopamidol on a molar basis, but that the nephrotoxic potential of the two radiocontrast agents is similar when comparison is based upon iodine content.     

Syringomyelia associated with a foramen magnum meningioma

In a 14-year-old boy with a meningioma at the foramen magnum extending to C-2, cervical syringomyelia was found on metrizamide computed tomographic myelography. The mechanism of syrinx enhancement on delayed computed tomographic scanning was considered to be due to transneural passage of metrizamide into the spinal cord. Long-standing spinal block may be responsible for development of syringomyelia. Syringomyelia associated with spinal extramedullary tumors was reviewed in the literature.     

Evaluation of cerebrospinal fluid rhinorrhea by metrizamide computed tomographic cisternography

Seven interesting and instructive cases of cerebrospinal fluid rhinorrhea evaluated by metrizamide computed tomographic cisternography are presented. The rhinorrhea was spontaneous in three patients and was related to previous head trauma or surgical procedures in four patients. The anatomical site and the extent of the fistula were demonstrated precisely by directly showing metrizamide passing through the bony defect. A combination of bone dehiscence and metrizamide within the adjacent paranasal sinuses or the nasal cavity is also useful in localization. Distortion of the interhemispheric fissure, sylvian fissure, or basal sulci indicates the probability of brain herniation through the defect.     

Comparison of Toxicity of Radiocontrast Agents to Renal Tubule Cells in Vitro

We have previously reported that radiocontrast agents induce direct renal tubule cell toxicity in vitro. The observed toxic effects were markedly potentiated by concomitant hypoxia. In addition, we have reported that the ionic radiocontrast agent diatrizoic acid is more toxic than the nonionic radiocontrast agent iopamidol in this system. Using suspensions enriched in rabbit renal proximal tubule segments, we compared the direct toxicities of the ionic dimeric ioxaglic acid to the nonionic monomeric compound iopamidol. Toxicity was assessed by comparing tubule potassium and calcium content, ATP levels, and respiratory rates after exposure to clinically achievable concentrations of radiocontrast agents. Ioxaglate (25 mM) produced significant declines in tubule cation content and respiratory rate with 30 min of hypoxia followed by 60 min of reoxygenation compared to molar-equivalent concentrations of iopamidol under similar conditions. Meglumine, a cationic compound frequently present in ionic contrast agent solutions, and ioxaglate tubule toxicity was additive. Iopamidol and ioxaglate exhibited similar tubule cell toxicity when comparison was based on iodine content. These experimental results suggest that the intrinsic nephrotoxic potential of ioxaglic acid is greater than that of iopamidol on a molar basis, but that the nephrotoxic potential of the two radiocontrast agents is similar when comparison is based upon iodine content.     

Percutaneous minidose metrizamide endomyelographic computed tomography in syringomyelia

Two patients presented with syringomyelia, each unusual. After neuroradiographic diagnosis with delayed metrizamide computed tomography (CT) or magnetic resonance imaging (MRI), an interesting diagnostic question arose. A percutaneous minidose metrizamide endomyelographic CT (PMDMECT) study clarified each situation and directly affected the neurosurgical approaches. The features of each case, the technique of PMDMECT, and postoperative follow-up data are reported.     

Computed tomographic cisternography with iopamidol in the diagnosis of primary empty sella

Twenty-one patients with primary empty sella were studied with computed tomography iopamidol cisternography. Ten milliliters of iopamidol at a concentration of 200 mg I/mL was administered intrathecally via the lumbar route. Eleven patients had a partial and 10 a complete empty sella. In six cases the third ventricle had prolapsed to the level of the interclinoid plane. There was no relationship between the clinical presentation and the grade of empty sella. The quality of the images obtained was always good or excellent. Cisternographies were performed in all of the patients although in 13 of them the correct diagnosis could have been achieved with a standard contrast-medium-enhanced computed tomography scan. The overall complication rate was 29%. Four patients (19%) had mild headaches and nausea; two patients (10%) had more severe side effects: vomiting, discomfort, and meningism. Computed tomographic cisternography with low-concentration iopamidol is a safe diagnostic procedure that allows a definite visualization of the anatomic alterations that occur in patients with empty sella. We think that this procedure should always be employed in symptomatic patients.