Role of autocrine stimulation for the effects of cyclic AMP on protein and lipid phosphorylation in platelets activated by particles.

We have compared responses in platelets stimulated with the particulate materials, Intralipid (liposome-suspension) and a potential contrast medium IEEC (1'-(ethyloxycarbonyloxy)-ethyl-5-acetyl-amino-3-(N-methyl-acetyla mino)-2,4,6-triiodo-benzenecarboxylate coated with human serum albumin), with and without forskolin and inhibitors of autocrine stimulation (IAS: an ADP-removing system of creatine phosphate/creatine phosphokinase; RGDS to prevent fibrinogen/fibronectin binding to GPIIb/IIIa; SQ 29.548 as a TXA2 receptor antagonist; cyproheptadine as a serotonin receptor antagonist; BN 52021 as a platelet-activating factor receptor antagonist). The pattern of tyrosine-phosphorylated proteins, phosphorylation of initial lipids and phosphorylation of pleckstrin (P47) were used as markers for early signal transducing responses, while secretion of ADP+ATP and beta-N-acetyl-glycosaminidase were used as final responses. Intralipid showed no platelet activation except for some weak tyrosine protein phosphorylation that was inhibited by elevated cAMP. IEEC induced strong platelet activation that was partly inhibited by increased levels of cAMP and IAS. The inhibition of elevated cAMP seemed to be due to removal of the G protein-mediated activation from secreted autocrine stimulators either by IAS or forskolin. The remaining activity is a pure effect from IEEC which is not affected by elevated cAMP.

A comparison between IEEC, a new biodegradable particulate contrast medium, and iohexol in a tumor model of computed tomography imaging of the liver.

RATIONALE AND OBJECTIVES: Higher contrast between normal and pathologic tissues in the liver may enable detection of smaller lesions in computed tomography (CT). This can be obtained using a liver-specific contrast medium. The authors evaluate a new agent, IEEC (1'-Ethyloxycarbonyloxy)-ethyl-5-acetylamino-3-(N-methyl-acetylami no)-2,4,6- triiodo-benzenecarboxylate), in an animal model, as a potential contrast agent for CT scanning of the liver. The IEEC particulate contrast medium used is based on a prodrug ester design of metrizoic acid and accumulates rapidly in the liver. The particles are quickly degraded into well-known metabolites and excreted from the body. METHODS: Two groups of rabbits were inoculated with VX2-carcinoma directly into the liver by laparotomy. Computed tomography imaging studies were carried out 9 and 11 days after the inoculation. The investigation was designed as a crossover study. The first group was imaged both as controls (without contrast medium) and with the particulate contrast medium on the 9th day and with iohexol on the 11th day. The second group was imaged with iohexol on the 9th day and as controls, and with the particulate contrast medium on the 11th day. The contrast medium was administered in a dose of 100 mgI/kg. Iohexol was administered in a dose of 570 mgI/kg according to a standard clinical scheme in use at a radiology department for dynamic CT. Changes in normal liver/lesion contrast and the conspicuity of tumors were assessed. On completion of imaging studies on day 11, all animals were killed. The liver was removed and evaluated for the presence of tumors. RESULTS: At macroscopic inspection, all rabbits were found to have tumors ranging from 2 to 14 mm in diameter. The size and location of the tumors corresponded well with the CT images. In the images where the particulate contrast medium was used, the attenuation in the normal liver parenchyma and the contrast between normal liver and lesion was significantly higher compared with the images where iohexol was used or the controls. For all tumor sizes, the lesion detection capability with the particulate contrast medium was significantly higher compared with iohexol (P < .005) and controls (P < .05). CONCLUSIONS: VX2-carcinoma in rabbit liver is a useful model for studying the efficacy of contrast media in CT imaging. The particulate contrast medium IEEC improved visualization of liver tumors.

Contrast enhancement of liver parenchyma and biliary tract related to liver function at delayed computed tomography.

Computed tomography (CT) of the liver was performed in 53 patients before, during and 4 to 6 hours after intravenous administration of approximately 60 g of iodine in metrizoate. At delayed CT, contrast medium was observed in the extrabiliary ducts in 20 patients (38%) and in the gallbladder in 28 (68%) of the 41 patients with no previous cholecystectomy. The increase in attenuation of liver parenchyma at delayed CT compared with the non-enhanced baseline CT ranged between 2 and 26 HU (mean 13.9). The material was divided into three groups with regard to liver function: normal, intermediate and pathologic. In the normal group contrast medium was observed in the gallbladder in 81 per cent and in the bile ducts in 57 per cent and the mean increase in attenuation of the liver parenchyma was 14.5 HU. In the pathologic group the same parameters were 40 per cent, 7 per cent and 10.6 HU, respectively. Contrast medium in the gallbladder and biliary ducts improved the information about anatomy. Pathology of the gallbladder and tumour growth along the hepatoduodenal ligament were better demonstrated. Delayed CT is a simple and non-invasive technique that may improve planning of liver surgery.

Comparison of non-enhanced, bolus enhanced, and delayed scanning techniques in computed tomography of hepatic tumours.

Non-enhanced, bolus contrast medium enhanced and 4 to 6 hours delayed computed tomography of the liver was performed in a prospective study of 53 patients. Forty patients had focal lesions, in 12 of these they were hypervascular. Contrast medium was administered as an initial bolus followed by a rapid injection of meglumine metrizoate (Isopaque Cerebral). The total iodine dose varied between 56 and 63 g, which gave an average increase in attenuation of 14 HU in normal parenchyma comparing delayed with non-enhanced scanning. Presence and extent of focal lesions were evaluated in a randomized and independent analysis by two radiologists. The percentage of examinations with correct tumour description was higher with bolus scanning (observer I 73%, observer II 75%) and delayed scanning (observer I 75%, observer II 78%) than with non-enhanced scanning (observers I and II 67%). An optimal bolus technique requires an exact timing of the contrast medium administration and scanning. Delayed scanning provides an excellent supplement when the bolus examination is suboptimal or shows equivocal findings.

Effects on the ATP content of cultured cells after radiographic contrast media exposure. Evidence for accumulation of contrast media in cultured cells.

The ATP content of cultured cells after exposure to meglumine-calcium metrizoate, sodium metrizoate, iohexol, iopamidol and saline was studied. Initially, the ATP content diminished rapidly for a short period and thereafter slowly during the incubation. After incubation with contrast media or saline, the ATP content slowly increased to normal when the cells were reincubated with fresh nutrient medium. Different contrast media and saline with the same final osmolality produced a similar effect on the ATP content of the cultured cells. Cellular association of meglumine-sodium diatrizoate, sodium metrizoate, sodium-iothalamate, iohexol and iopamidol was also examined. The established cell line NHIK 3025 as well as primary cultures of human umbilical endothelium were found to accumulate contrast media in a time- and concentration-dependent manner. When the incubation was carried out at 4 degrees C, the cellular accumulation of contrast medium was less than 35 per cent of that seen at 37 degrees C. It therefore seems that energy-dependent processes are involved to some degree.

Effects of radiographic contrast media on monolayer cell cultures.

The relationship between iodine concentration, osmolality, and toxicity for nine different contrast media was studied. High osmolal conventional ionic contrast media (Na-metrizoate, Na-iothalamate, meglumine/Na-diatrizoate, meglumine-calcium-metrizoate) and the new low osmolal nonionic (Metrizamide, iopamidol, iohexol) and ionic dimer (Meglumine/Na-ioxaglate) contrast media were tested. Monolayer cell cultures of human cervical carcinoma in situ cells were used as a test system. The toxicity of contrast media on cell cultures was strongly dependent on the osmolality, and different contrast media with the same osmolality had about similar effects on the cell cultures. However, contrast media seem to have some additional and more specific effects since equiosmolal saline and mannitol were better tolerated. When the toxicity was related solely to iodine concentration it emerged that the new low osmolal contrast media were much better tolerated than the high osmolal conventional contrast media.

Herniography in the diagnosis of obscure groin pain.

Obscure groin pain was investigated in 250 consecutive patients (including 171 males) with no palpable hernia or previous hernia operation. Herniography revealed nonpalpable but symptomatic hernia in 51% of the male and 21% of the female patients. Among the hernia patients with bilateral pain, 40% had unilateral hernia. Direct-type hernia was most commonly found. Of the surgically treated patients, 87% were free from groin pain postoperatively. Further clinical investigations with a broad diagnostic approach gave a treatable diagnosis in 70% of the patients without hernia surgery. Spontaneous improvement occurred during the investigation in 25%, and the cause of groin pain remained unclear in 5% of the patients. Herniography is a valuable diagnostic tool in obscure groin pain and its use is justified at an early stage of investigation. "Blind" exploration can thus be avoided.

Comparative double-blind investigation of meglumine metrizoate, metrizamide, and iohexol in carotid angiography.

The new nonionic contrast medium iohexol (Omnipaque) was compared with its predecessor metrizamide (Amipaque) and with the conventional ionic medium meglumine metrizoate (Isopaque Cerebral) in carotid angiography using a double-blind crossover technique. The results indicated that iohexol and metrizamide caused less discomfort than the ionic medium. The circulatory effects of the three media were generally mild, and the diagnostic effectiveness was comparable when the iodine concentration was kept in the range of 280-300 mg I/ml.

Iohexol compared to meglumine-Ca-metrizoate in common carotid angiography. A randomized double blind cross-over study in man.

A randomized double blind cross-over study with iohexol (Omnipaque) and meglumine-Ca-metrizoate (Isopaque cerebral) was performed to answer questions concerning subjective side effects and tolerability that arose from a double blind parallel study with the same two media. The cross-over study design, with injection of the contrast media under identical conditions in the same artery, seems to be the most practical method of comparison of two well tolerated media. Iohexol showed significantly less side effects than meglumine-Ca-metrizoate. The routine premedication with atropine was neglected in this study to evaluate effects on heart rate due, for example, to the toxicity of the media. Small tachycardial and bradycardial reactions were equally divided between the media. However, a short asystolic period following the injection of meglumine-Ca-metrizoate in two different patients may indicate a higher toxicity of this medium.

Fatal reaction following renal angiography and biopsy in diabetic patients with Azotemia.

Severe reactions to contrast media in two diabetic patients with azotemia are described. Both patients also showed signs of immunopathy. The reaction was fatal in one of them. Little is known about contrast media reactions and their natural history. Patients with diabetes mellitus and impaired renal function should be studied with caution and with careful consideration of the indication for the procedure. If an examination with contrast media is considered unavoidable, all diabetic patients with renal failure should be supervised closely to detect the development of acute renal failure. Dehydration should be avoided. Careful monitoring of blood glucose, serum electrolytes, serum creatinine and blood pressure will aid in the early detection of the adverse reaction.

Ruptured Baker's cyst: a radiological diagnosis.

Rupture of a Baker's cyst may mimic thrombophlebitis of the leg clinically. Differentiation of these two entities is important because of therapeutic implications. A history of previous disease involving the knee, especially rheumatoid arthritis, or the finding of joint effusion are suggestive of the diagnosis of ruptured Baker's cyst. This may be confirmed by arthrography. We describe a series of eight patients with the "pseudothrombophlebitis" syndrome. Arthrography showed seven as having a ruptured Baker's cyst, while in one an intact cyst was found.