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Biomedical subjects

S E Ekholm

Publications and source records attributed to S E Ekholm.

At least 19 recordsLinked to original sources
PubMed2001

MRI staging using gadodiamide for soft-tissue tumors of the head and neck region. Results from a phase II trial and a 5-year clinical follow-up.

In order to document the safety, tolerability and efficacy of gadodiamide outside CNS, an open, non-drug comparative study was performed in patients with tumors of the head and neck region. Fifty adult patients were included and 48 patients received the contrast medium. The examinations were performed on a 1.5 T imager using transverse, non-enhanced T1- and PD-/T2-weighted conventional spin-echo sequences, followed by a contrast-enhanced transverse T1-weighted sequence. Post-contrast images provided more diagnostic information compared to unenhanced images in 33 of 48 patients (69%). This information was of significant help in four and of moderate help in 14 cases. Post-contrast images compared to non-enhanced T1-weighted showed improvement in lesion delineation for 29 of the 43 patients where a lesion was observed. Only in two patients was the diagnostic information lower post-contrast. A comparison between all pre-contrast images versus contrast medium enhanced showed post-contrast images to give more diagnostic information in 14 and less in nine patients. No patient experienced discomfort in relation to gadodiamide injection. Only one adverse event occurred which was described as thirst, being of moderate intensity. The 5-year clinical outcome was analyzed and compared with the pre-operative staging. The case-books of all patients were reviewed and in 44 patients all information could be found. Of those, 18 were still alive, one with active disease (AAD) and 17 with no evidence of disease (NED). Two of those four patients, where information was incomplete, showed NED and two had died. This trial showed that contrast-enhancement using gadodiamide for evaluation of soft tissue tumors in the head and neck region was safe and provided statistically significant more diagnostic information compared with unenhanced images. MRI, when compared with palpation/inspection, changed tumor staging in approximately 30% of all cases.

Contrast Media↗
PubMed1992

Effects of radiopaque contrast media on calcium uptake and phosphatidylinositol metabolism in rat brain synaptosomes.

Radiographic contrast media (RCM) used in the subarachnoid space are associated with occasional adverse reactions. This study examines the possibility that RCM reactions are caused by interactions with the plasma membrane phosphatidylinositol (PI) second messenger system. Isolated nerve endings, known as synaptosomes, were produced from rat brain homogenates. The synaptosomes were then incubated with RCM to determine if 32Pi labeling of the PIs or the uptake of 45Ca were influenced in a manner consistent with known mechanisms. The RCM metrizamide, iopamidol, iodixanol, and iotrol (but not iohexol) increased the 32Pi labeling. Hyperosmolality produced large increases in phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4, 5,-bisphosphate (PIP2) labeling. In the non-depolarized state iodixanol, but not metrizamide or iohexol, caused a time-dependent increase in 45Ca uptake. Iodixanol, iohexol, and metrizamide also augmented the veratrine-stimulated uptake of calcium, but none of the RCM affected the uptake of Ca resulting from potassium depolarization. The increased 32Pi labeling of the PIs caused by RCM is not directly related to Ca uptake, because the direction of change is wrong. RCM perturbations of the plasma membrane may cause an inhibition of other membrane components and systems. Hyperosmolality also may cause inhibition of membrane components. It is not known if these effects are important in clinically observed RCM toxicity.

Animals↗
PubMed1991

The effects of gadolinium-DTPA and -DOTA on neural tissue metabolism.

Gadolinium DTPA and DOTA are being used extensively for imaging blood-brain barrier lesions. This study was performed to determine clinically relevant blood, cerebrospinal fluid (CSF), and neural tissue concentrations of these agents, and to determine if they alter neural tissue glucose metabolism. Bolus injections of 0.2 mmol Gd-DTPA/kg were made in rabbits, and blood, CSF, and neural tissue Gd concentrations were measured using atomic emission. Rat hippocampus slices were incubated for 6 hours in solutions of Gd-DTPA and Gd-DOTA, and effects on the production of carbon-14-labeled CO2 from glucose determined. Plasma concentrations reached a peak of 2.46 mmol at 1 minute postinjection, and dropped to 50% of peak in 6 minutes. The highest CSF concentration observed was approximately 0.1 mmol, and the mean lumbar cord concentration was approximately 8.5 mumol/g. Gd-DTPA and Gd-DOTA concentrations greater than 1.0 mmol caused significant increases in CO2 production. In areas of blood-brain barrier lesions, Gd-DTPA and Gd-DOTA may cause changes in tissue metabolism; however, in other areas it is much less likely.

Animals↗
PubMed1990

Local glucose utilization changes caused by subarachnoid contrast media in the rabbit.

The glucose metabolism effects of six hour exposures to subarachnoid injections of metrizamide, iohexol, iodixanol and control solutions were studied in vivo in 18 rabbits. The brain tissue uptake of intravenously injected 14C labelled deoxyglucose was measured using autoradiographic techniques. Metrizamide and iodixanol caused significant (p less than 0.05) decreases in deoxyglucose uptake in the outer cortical areas where the contrast medium concentrations were highest. Iohexol and the control CSF solution did not cause significant effects. The results appear to indicate that iohexol has less effect on brain tissue glucose metabolism than either metrizamide or the new non-ionic dimer iodixanol.

Animals↗
PubMed1989

Effects of contrast media on neural tissue glucose uptake in vitro.

The authors previously showed that metrizamide causes an inhibition in CO2 production in rat neural tissue. The purposes of this work were to test if this inhibition was the result of a competitive inhibition of metrizamide with the D-glucose transport system and to test the effect of other contrast media. Deoxyglucose was used as a marker for glucose. The first cellular system using rat hippocampus slices was designed to examine the effect of 15 mM and 80 mM metrizamide on deoxyglucose uptake. The second cell-free system, using isolated rat brain synaptosomes, was designed to evaluate more accurately the mechanism and kinetics of metrizamide's inhibitory effect on the uptake of deoxyglucose and to compare metrizamide to other nonionic contrast media (iohexol, iopamidol, iotrol, and iodixanol). These experiments demonstrate that there is inhibition of D-glucose uptake only in hippocampus slices and that the inhibition is dependent on the concentration of metrizamide. This does not, however, appear to be a competitive inhibitory effect on the carrier such as that between D-glucose and 2-deoxy-D-glucose. In synaptosomes, none of the contrast media had a significant effect on the uptake of 2-deoxyglucose.

Animals↗
PubMed1988

Observations on cerebral computed tomography in patients having carotid endarterectomy.

A review was undertaken of all patients seen in our institution between January 1978 and March 1987 in whom a cerebral CT scan was obtained in association with elective carotid endarterectomy. Three hundred fifty-nine such patients were identified. In a subgroup of 89 patients who were neurologically normal after carotid endarterectomy, scans were performed at least 48 hours after surgery to quantitate the incidence of silent postoperative infarction. These scans were interpreted by one neuroradiologist. Preoperative cerebral CT scans showed ipsilateral infarction in 146 of 359 patients (40.6%). Ipsilateral infarction was most common in patients with stroke (76%) but was also seen in 32.8% of patients with transient ischemic attacks, in 9 of 40 patients (22.5%) with nonhemispheric symptoms, and in 9 of 45 patients (20%) with asymptomatic hemodynamically significant carotid stenosis. The postoperative stroke rate was not significantly increased by the presence of infarct on preoperative cerebral CT scan (2.6% vs 1.9%). New infarcts were seen on cerebral CT scanning after carotid endarterectomy in 2 of 89 patients with no detectable neurologic abnormality (2.3%). This study demonstrates a high frequency of ipsilateral infarction in patients having elective carotid endarterectomy, even in those patients with clinical symptom complexes thought by many physicians to be relatively benign (i.e., transient cerebral ischemia, nonhemispheric ischemia, and asymptomatic carotid stenoses).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

In vitro models for testing the metabolic effects of myelographic contrast media.

Water-soluble nonionic x-ray contrast media have greatly improved the quality and safety of myelography. Toxic side effects are still observed however. The side effects are generally worse with the first nonionic agent, metrizamide, which has a glucoselike side group. Two in vitro models were developed to examine the effects of contrast media on glucose metabolism. Using rat hippocampus slices, the authors observed significant depression of carbon dioxide production by metrizamide and by deoxyglucose, a known metabolic inhibitor. Iohexol and iopamidol did not cause significant depressions. In rat brain synaptosomes the authors did not observe a depression of the uptake of deoxyglucose 14C by any media tested. These studies indicate that metrizamide can create metabolic depression but that it does not compete with glucose for the membrane glucose carrier.

Animals↗
PubMed1987

Further support for the glucose hypothesis of metrizamide toxicity. The effect of metrizamide and glucose analogue-free contrast media on hexokinase.

Metrizamide neurotoxicity has been hypothesized to be caused by an inhibitory effect of the drug on glucose metabolism. Metrizamide contains a glucose side chain, and glucose analogues including metrizamide have been shown to be inhibitors of hexokinase, an enzyme that is central to cerebral glucose metabolism. We studied the effect of the nonionic contrast agents iohexol, iotrol, and iopamidol, and the ionic contrast meglumine diatrizoate, on hexokinase in vitro. Although metrizamide reproducibly caused competitive inhibition of the reaction, the nonglucose contrast agents had no significant effect on the enzyme. These results add further support for the glucose hypothesis of metrizamide neurotoxicity.

Contrast Media↗
PubMed1987

High-dose iohexol myelography.

Lumbar myelography was performed with high volumes of iohexol (15-24 ml) at a concentration of 180 mgI/ml (average dose, 20 ml) in 48 patients. In 44 patients receiving more than the currently recommended upper dose limit of 17 ml, the frequency of headache (41%), nausea (14%), and vomiting (9%) was comparable to results for routine-dose lumbar metrizamide myelography. Overall, adverse reactions were more frequent, particularly at the highest dose levels, than reported for conventional-dose iohexol myelography. However, there were no occurrences of neuropsychiatric disorder, encephalopathy, or seizure. High-dose technique allows superior visualization of upper lumbar and conus detail and may be advantageous in patients with large subarachnoid spaces and in multi-level examinations. This study supports the results of previous trials that suggested the relative safety of iohexol as a contrast agent and extends those observations to a higher dose range. Because of the increased rate of adverse reactions at the highest dose levels (despite the absence of major adverse reactions), iohexol should continue to be used conservatively, with doses carefully tailored to each examination.

Adult↗
PubMed1986

Postoperative radiographic appearance of intracranial hemostatic gelatin sponge.

Hemostatic gelatin sponges were placed in hemispheric defects created in four dogs which were then periodically scanned by computed tomography to determine the postoperative appearance of the sponges. The hemostatic sponges appeared as low attenuation regions for 7-10 days. The attenuation value of these Gelfoam cavities was intermediate between fat and air. Subsequently, clinical cases were selected in which the location of gelatin sponges were known to demonstrate the appearance of the material in patients. In addition to enhancing the accuracy of computed tomographic interpretation, we have found that the gelatin sponge can be useful as a transient computed tomography marker for localization of surgical activity.

Adolescent↗
PubMed1986

Penetration of subarachnoid contrast medium into rabbit spinal cord. Comparison between metrizamide and iohexol.

The penetration into rabbit spinal cord of two nonionic contrast media, iohexol and metrizamide, and a reference tracer, technetium DTPA, were compared. The spinal subarachnoid space was perfused for 4 hours with a CSF solution to which technetium DTPA and either iohexol or metrizamide had been added. The contrast media and technetium DTPA concentrations reached a plateau level in CSF outflow within 80 minutes. The contrast media concentrations in CSF were higher than the technetium DTPA (P less than .001). In the cord tissue, technetium DTPA reached higher concentrations than the contrast media (P less than .001), and iohexol reached higher concentrations relative to technetium DTPA than metrizamide (P less than .001). The mean contrast media distribution volumes in the thoracic cord were 13% (iohexol) and 12% (metrizamide). The smaller distribution volume observed for metrizamide could be related to the larger effective size of "associated" metrizamide molecules or an interference with diffusion perhaps related to binding to glucose carriers.

Animals↗
PubMed1986

Iopamidol and neural tissue metabolism. A comparative in vitro study.

Metrizamide was the first water-soluble contrast medium with a neurotoxicity low enough to allow it to be used routinely in the entire subarachnoid space. However, neurologic complications are still observed in some patients following the use of metrizamide. The cause of this toxicity has not been established, but existing evidence suggests an interference with glucose metabolism. In previous studies, a depression in CO2 production in neural tissue slices was demonstrated when isotonic metrizamide was added but not isotonic iohexol. In addition to iohexol, there is another new, nonionic, monomeric, water-soluble CM, iopamidol, soon to be released for clinical use in the United States. Iopamidol, like iohexol, has shown fewer adverse reactions and seems to be safer for myelography than metrizamide. Direct comparative studies of iopamidol and iohexol are sparse and the cause of their toxicity is not yet understood. This study was performed to determine the effect of iopamidol on neural tissue glucose metabolism as compared with the effects of iohexol and metrizamide. Metrizamide decreased CO2 production in neural tissue slices by 23%. Iopamidol and iohexol did not produce significant depression. Moreover, this model could not demonstrate any significant difference between iopamidol and iohexol in direct comparisons. The new monomeric contrast media, iopamidol and iohexol, thus do not appear to interfere with glucose metabolism. Adverse reactions to these new media are most likely caused by other mechanisms.

Animals↗
PubMed1986

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↗
PubMed1986

The effect of subarachnoid metrizamide and iohexol on cerebral glucose metabolism in vivo.

We studied the effect of metrizamide and iohexol on local cerebral glucose utilization (LCGU) using autoradiography. Metrizamide or iohexol was introduced into the subarachnoid space of rabbits and positioned over the right hemisphere for 3 or 6 hours. Using the unexposed (left) hemisphere as an internal control, we calculated relative changes in LCGU. In the three metrizamide-exposed animals the LCGU was decreased over the contrast media-exposed right temporoparietal cortex (L-R difference was positive). There was no significant changes in LCGU and no positive L-R difference after treatment with iohexol (three animals). We conclude that metrizamide does affect glucose metabolism in vivo, and this effect is dependent on localization of the contrast medium. The clinically safer drug, iohexol, in similar concentration and higher osmolality, did not decrease glucose metabolism.

Animals↗