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Functional and physical characteristics of rat Leydig cell populations isolated by metrizamide and Percoll gradient centrifugation.

The physical and functional properties of Leydig cell populations obtained by centrifugation of testicular cells in two different density gradient media, Percoll and Metrizamide, were compared. Percoll-gradient centrifugation yielded two Leydig cell bands (Peak I and Peak II) that were comparable, as to their density and testosterone-producing capacity, to the respective Leydig cell bands, Population I and Population II, isolated in a Metrizamide gradient. The denser Leydig cell band (II) had a greater capacity for testosterone production than the less dense band (I), regardless of the type of gradient used for its isolation. Metrizamide gradient centrifugation separated the majority of germ cells from the "light" (Population I) Leydig cells, whereas in the Percoll gradient, germ cells comigrated with Peak I Leydig cells. Leydig cell separation by Percoll gradients was highly dependent on the presence of Ca2+ and Mg2+ in the medium, while these cations had no effect on the separation of Leydig cells by Metrizamide. In conclusion, Metrizamide gradient centrifugation yielded two Leydig cell populations of similar functional and physical properties to the respective populations isolated in Percoll gradients.

Animals↗

CT-determined canine kidney and urine iodine concentration following intravenous administration of sodium diatrizoate, metrizamide, iopamidol, and sodium ioxaglate.

Following 24-hour fasting and fluid deprivation, sequential changes in CT numbers of the canine kidney were determined in 4 dogs, each of whom received, at intervals, IV sodium diatrizoate, metrizamide, iopamidol, and sodium ioxaglate at a dose of 500 mgI/kg body weight. The urinary bladder was catheterized for baseline determination of urine osmolality and, subsequently, urine volume and CT number, CT number of the bladder urine from 0 to 10 minutes and from 10 to 20 minutes post-injection was obtained by scanning known dilutions of urine in vitro. Peak renal cortical enhancement occurred within 2 minutes of bolus injection and was not dependent on the chemical make-up of the contrast agent. Peak medullary enhancement occurred within 3 minutes of bolus injection. Peak medulla CT number following sodium diatrizoate was significantly less than that following metrizamide (P less than 0.025) or iopamidol (P less than 0.01). Peak medulla CT number was significantly less following sodium diatrizoate (P less than 0.01), metrizamide (P less than 0.01) and iopamidol (P less than 0.05) than following sodium ioxaglate. Urine iodine concentrations followed a similar pattern, with significant differences as follows: sodium diatrizoate less than metrizamide = iopamidol less than sodium ioxaglate. It was concluded that the investigational agents metrizamide, iopamidol, and sodium ioxaglate have theoretical advantage for excretory urography. Differences in renal handling of these agents are detectable, with CT scanning as differences in renal medullary enhancement and urine iodine concentration.

Animals↗

Iohexol vs. metrizamide in studies of glucose metabolism. A survey.

Nonionic contrast media represent a significant advance for myelography due to their substantially lower neurotoxicity. Some side effects have been noted with metrizamide, however. Origins of adverse effects have not been clearly defined. Studies reviewed here investigated the effects of two nonionic contrast media, metrizamide and iohexol, on glucose metabolism in neural tissue cells in vitro using rat hippocampal tissue slices. Isotonic metrizamide produced metabolic disturbances that may partially explain some clinical adverse effects. It was hypothesized that iohexol, which, unlike metrizamide, does not contain a 2-deoxy-D-glucose component, would not have this effect. A series of in vitro experiments compared the two media. Results showed no evidence that iohexol caused metabolic disturbances, but in vitro there was a depressive effect on metabolism from hypertonicity. In vivo water will rapidly diffuse toward hypertonic areas, thus neutralizing the osmotic effect. The lesser metabolic effect suggests that iohexol would be safer than metrizamide for subarachnoid examinations.

Animals↗

Modification of periventricular hypodensity in hydrocephalus with ventricular reflux in metrizamide CT cisternography.

An analysis of metrizamide computed tomography (CT) cisternographic findings in cases of communicating hydrocephalus has been carried out. Serial observations of the density in the periventricular area in 19 cases with metrizamide ventricular reflux have revealed the following different patterns: (a) precontrast periventricular hypodensity diminishing after CT cisternography and possibly indicating transependymal metrizamide migration (two cases); (b) periventricular hypodensity unchanged (two cases); (c) minimal periventricular hypodensity with slight rise in its attenuation values after ventricular metrizamide reflux (four cases); and (d) no periventricular hypodensity and no change after reflux (six cases). Our preliminary experience indicates that the presence of periventricular hypodensity with an increase in its attenuation values following ventricular reflux of metrizamide is possibly a criterion that may be used in favor of a cerebrospinal fluid shunting operation.

Adult↗

Competitive inhibition of rat brain hexokinase by 2-deoxyglucose, glucosamine, and metrizamide.

The effects of metrizamide on the kinetics of rat brain hexokinase were compared in vitro with those of 2-deoxyglucose and glucosamine. Although metrizamide, 2-deoxyglucose, and glucosamine are known to be competitive inhibitors of approximately equal potency for glucose of yeast hexokinase (Ki approximately 0.7 mM for all three), metrizamide is a much weaker competitive inhibitor (Ki about 20 mM) of rat brain hexokinase than either 2-deoxyglucose or glucosamine (Ki about 0.3 mM for both). This indicates a greater active site specificity of rat brain hexokinase than of yeast hexokinase. Rat brain hexokinase activity is enhanced approximately threefold in the presence of 0.05, 0.2, and 0.8 mg/ml bovine serum albumin, while yeast hexokinase is only enhanced by 50% under these conditions. Despite the high Ki value for metrizamide, interference with glucose metabolism may occur whenever metrizamide is present in much higher concentrations than glucose. Myelography in humans is one such situation.

Animals↗

Experience with metrizamide in patients with previous severe anaphylactoid reactions to ionic contrast agents.

Metrizamide was employed in six patients who, during angiography, had had severe anaphylactoid reactions to conventional ionic contrast media. Five of these patients had received corticoid premedication before injection of both conventional contrast medium and metrizamide; anaphylaxis occurred only after administration of conventional contrast media. Four patients had no detectable reaction whatsoever after metrizamide; a fifth had only transient tachycardia. In the sixth patient, delayed edema developed in the region of his cerebral arteriovenous malformation. These observations suggest a marked decrease in the incidence and severity of anaphylactoid reactions when metrizamide is substituted in patients who have reacted to ionic contrast media. Metrizamide, or a comparable nonionic contrast agent, should be strongly considered in patients who have had a severe reaction to conventional contrast medium.

Adolescent↗

Arachnoid response to contrast media: a comparison of iophendylate and metrizamide in experimental animals.

Arachnoiditis resulting from administration of intrathecal iophendylate (Pantopaque) was compared with that from metrizamide (Amipaque) in 16 monkeys. Four animals initially underwent metrizamide myelography, eight underwent iophendylate myelography, and four control animals received only cerebrospinal fluid. Twelve weeks later, all 16 animals underwent metrizamide myelography and then histologic studies. Animals receiving iophendylate for the first myelogram differed significantly from the other two groups on inflammation, fibrosis, and myelographic evidence of arachnoiditis. The arachnoiditis produced by iophendylate was more severe than that produced by metrizamide; the iophendylate also produced a more cellular reaction that was qualitatively different from the reaction to metrizamide. This more severe reaction to iophendylate has clinical implications for patients undergoing myelography if the contrast medium is not completely removed from the system after myelography.

Animals↗

The cardiovascular effects of metrizamide in infants.

A prospective study was performed in 30 children under 3 years of age to compare the cardiovascular effects of a nonionic contrast material of low osmolality, metrizamide, with those of a conventional ionic contrast material, meglumine sodium diatrizoate. Left ventricular end-diastolic pressure, left ventricular peak systolic pressure, heart rate, echocardiographically obtained end-diastolic and end-systolic dimension, and blood chemistries were obtained before and after angiography. Neither contrast material changed serum sodium, potassium, or creatinine levels. However, serum osmolality rose significantly following injection of diatrizoate, but not metrizamide. Both end-diastolic and end-systolic dimensions increased after diatrizoate injection. However, end-diastolic dimension was unchanged and end-systolic dimension fell after metrizamide infusion. Both contrast materials raised left ventricular peak systolic pressure and left ventricular end-diastolic pressure after injection; the magnitude of these pressure changes was the same for both agents. Heart rate increased with diatrizoate to a significantly greater degree than with metrizamide. There was no difference in the quality of radiographic opacification. It is concluded that although the effects on intracardiac pressures are similar for both contrast materials, metrizamide may be advantageous in the critically ill infant because it causes a smaller increase in osmolality, fewer changes in cardiac dimensions, and a reduced heart rate challenge.

Angiocardiography↗

Effect of metrizamide, a nonionic radiographic contrast agent, on human serum complement. Comparison with ionic contrast media.

The nonionic radiographic contrast material (RCM) metrizamide causes consumption of total complement activity in normal human serum (NHS) in vitro in the absence and to a lesser extent also in the presence of EDTA. The depression of titers of total complement is related to an inactivating effect of metrizamide on component C2. Furthermore, metrizamide induces activation of the alternative pathway as evidenced by the appearance of C3 and factor B cleavage products in NHS, dependent on the presence of divalent cations. Alternative pathway activation is probably mediated by an antagonizing effect of metrizamide on the inactivation of C3b. Unlike ionic RCM, the nonionic substance metrizamide does not lead to cleavage of the internal thiolester bond present in native C3 and C4, at concentrations that produce potent consumption of C3 activity in NHS.

Complement Activation↗

Competitive inhibition of brain hexokinase by metrizamide.

We compared the effect of metrizamide and its parent compound glucosamine on the kinetics of dog brain hexokinase. The Michaelis constant (Km) for glucose rose from 0.065 to 0.15 to 0.28 mM in the presence of 0, 16, and 32 mM metrizamide, respectively. For 0, 1.5, and 3.7 mM glucosamine, the Km values were 0.065, 0.4, and 1.3 mM. No change was found in the maximal velocity with either inhibitor. Metrizamide is therefore a rather weak competitive inhibitor of brain hexokinase. However, since the brain or spinal cord may be exposed to metrizamide concentrations near 780 mM during myelography, it is predictable that glucose metabolism may be significantly impaired under these conditions. This may be the mechanism for some cases of metrizamide encephalopathy.

Animals↗

Metrizamide inhibits human brain hexokinase.

The myelographic contrast agent, metrizamide, causes a temporary confusional state in many patients. Since metrizamide is a 2-deoxyglucose analogue, it was tested for inhibitory effects on glucose metabolism. The Michaelis constant (Km) of human brain hexokinase for glucose rose from 0.039 to 0.24 and 0.47 mM with final metrizamide concentrations of 0, 16 and 32 mM, respectively. The maximal velocity did not change. Since metrizamide is injected into the human CSF in concentrations of up to 780 mM, impairment of brain glucose metabolism can be expected. These effects could be largely counteracted if metrizamide were injected in a 100 mM glucose solution.

Animals↗

Cerebrospinal fluid rhinorrhea: evaluation with metrizamide cisternography.

Metrizamide computed tomographic cisternography was used to examine 27 patients (19 males and eight females, 14-59 years old) clinically suspected of having cerebrospinal fluid fistulae with rhinorrhea. Twenty-one fistulae were traumatic and six were spontaneous. Five to 6 ml of metrizamide (or lopamidol, two cases) were injected by lumbar puncture at a concentration of 185-200 mg I/ml for direct coronal and axial computed tomographic sections of the skull base. Cerebrospinal fluid rhinorrhea was present at the time of examination in 12 of 27 cases. Results were evaluated according to three criteria: (1) metrizamide passage through the bony and dural defect; (2) demonstrable site of the fracture and/or bony defect; and (3) metrizamide visualized within a paranasal sinus, nasal cavity, or cotton pledget. The examination was considered positive when criterion 1 alone was present and when 2 and 3 were associated. In 15 of 27 cases, cisternography was positive, with the exact site of cerebrospinal fluid leakage demonstrated in 10 patients. In six cases, the results were not definitive; only one of the criteria (2 or 3) was fulfilled. In six cases, cisternography was normal. Seventeen patients underwent surgery. The site of cerebrospinal fistulae was ethmoidal in nine cases, frontoethmoidal in seven, sphenoidal in two, and sphenoethmoidal in one. The relative value of metrizamide computed tomographic cisternography compared with other diagnostic studies, polytomography, positive or negative contrast studies, and radionuclides, is discussed. Diagnostic pitfalls include artifacts and partial volume effect.

Adolescent↗

Neurologic complications in diabetics after metrizamide lumbar myelography.

Recognized risk factors for metrizamide myelography are seizure disorder, seizure-threshold-lowering drugs, dehydration, and possibly age. After observing serious neurologic complications in diabetic patients after routine metrizamide myelography, a retrospective study was conducted to determine if diabetes should be considered another independent and important risk factor. Forty-one diabetic patients who had lumbar metrizamide myelograms were compared with a control group of 110 nondiabetic patients. A significantly higher incidence was found of severe vomiting (15% vs. 3%, p less than 0.01) and neurologic complications (20% vs. 2%, p less than 0.001) in the diabetic population. Neurologic complications included one case each of seizure, severe encephalopathy, auditory and visual hallucinations, and prolonged somnolence and four cases of confusion-anxiety. Four of the diabetic patients had major transient elevations of blood pressure. These findings suggest that diabetics are a high-risk population for metrizamide myelography. The dose of metrizamide should be minimized, whenever possible. The new nonionic myelographic agents may prove to be safer in this population, but caution and careful follow-up should be exercised in the initial trials with these patients.

Aged↗

A possible mechanism for the neural adverse reactions caused by metrizamide.

Causality of the metrizamide-induced neural adverse effects was explored among the effects on behavior, electroencephalogram (EEG), and brain glucose utilization in rats. Iotrolan, a new myelographic contrast agent, was used as a reference substance throughout the study. Supracortical subarachnoidal administration of metrizamide caused, within a few minutes, symptoms of sedation and anxiety, which were accompanied by appearance of slow wave or flattening in EEG not only of the cortex, but also of the regions of the hippocampus and thalamus. The rates of local cerebral glucose utilization (LCGU) in a wide range of the brain, measured by using 3H-2-deoxyglucose, were also altered significantly. Despite a limited distribution of metrizamide in the lateral region of the cortex, LCGU was suppressed significantly in the administered side of the parietal cortex, thalamus, subthalamic nucleus, medial geniculate body, and mammillary body and increased in the regions of hippocampus, caudate-putamen, and globus pallidus. It is concluded that, rather than inhibiting the hexokinase reaction in the brain cell, metrizamide appears to cause reduction of a net glucose transport into the cell and that this direct effect on the cortex is amplified and propagated, via neurotransmission, to the regions of the diencephalon and midbrain, causing secondarily various types of disturbance in the mental and motor functions. Iotrolan was proved to lack any biologic activity that may relate to the neural adverse effect observed with metrizamide.

Animals↗

Metrizamide compared with iohexol for cervical myelography: a double-blind study.

A double-blind comparative study of iohexol and metrizamide for use in cervical myelography through lumbar puncture was carried out in a group of 30 patients. No difference was found in the quality of radiographic examinations of the cervical or lumbar regions nor in the postmyelographic computed tomographic examinations of the cervical spine. The overall incidence of side effects was significantly higher in the metrizamide group (93.4%) than in the iohexol group (40%) (p = 0.002). The differences in incidence of nausea (53% in the metrizamide group compared with 13% in the iohexol group) and vomiting (46.6% with metrizamide, 6.6% with iohexol) were also significant (p = 0.02). Pyramidal signs and seizures occurred only after metrizamide myelography.

Adult↗

Arachnoiditis following myelography with metrizamide in monkeys. Effect of blood in the cerebrospinal fluid.

Monkeys were injected intrathecally with blood, metrizamide (Amipaque) or a mixture of blood and metrizamide. Twelve weeks later the animals were examined for evidence of arachnoiditis. Either blood or metrizamide alone in sufficient amounts resulted in arachnoiditis. The addition of blood to metrizamide did not alter the severity or risk of arachnoiditis from experimental myelography with metrizamide.

Animals↗

[Metrizamide encephalopathy in a child with hydrocephalus--effects of L-threo-DOPS on persistent disturbance of consciousness and L-dopa on extrapyramidal symptoms].

This report describes a case of metrizamide encephalopathy with persistent disturbance of consciousness and extrapyramidal symptoms. These two conditions have rarely been reported among the various adverse effects of metrizamide. An 11-year-old girl had been in almost good health until she was ten years old, at which time she received a ventriculo-peritoneal shunt operation, suffering from hydrocephalus of unknown etiology. At the age of eleven, she was admitted to our hospital due to hydrocephalus recurrence. She was examined by metrizamide shunt-gram (1200 mg iodide/4 ml). On the next day, she became drowsy. The CT scan disclosed the periventricular penetration of metrizamide into the medial part of the thalamus and the caudate nucleus. Thirteen days later, disturbance of consciousness continued, and extrapyramidal symptoms, that is, rigo-spasticity and postural tremor, were observed. Oral administration of L-threo-DOPS, the direct precursor of noradrenaline, was effective against the persistent disturbance of consciousness and L-DOPA was effective against the extrapyramidal symptoms. She soon recovered almost to normal and no neurological deficit remained. We thus conclude that the CT scan findings and effects of L-threo-DOPS and L-DOPA suggest that metrizamide encephalopathy in this case were respectively due to its periventricular penetration into the medial part of the thalamus and the caudate nucleus, and the resultant deficiency of the ascending noradrenergic reticular activating system and the nigrostriatal dopaminergic system.

Basal Ganglia Diseases↗

Application of metrizamide in the radiographic evaluation of the neurologically diseased patient.

Metrizamide (Amipaque) is a new water-soluble contrast agent for use in the intrathecal space. Extensive animal and clinical studies have demonstrated its low toxicity. The advantages to the use of metrizamide include the fact that it is miscible with cerebrospinal fluid and can fill narrow spaces, is sufficiently radiopaque to outline delicate structures within the central nervous system, is completely resorbed from the subarachnoid space, and, to date, has not been implicated in the formation of adhesive arachnoiditis. Application of metrizamide to the evaluation of neurologically diseased patients has included myelography, intracranial cisternography, and ventriculography, as well as various techniques in conjunction with computerized tomography. These various uses of metrizamide are discussed together with some indications and advantages. Metrizamide has now replaced Pantopaque and gas as the most commonly used intrathecal contrast agent at the University of Texas Health Science Center at Dallas.

Adult↗