Biomedical subjects
Publications and source records attributed to P Leander.
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A new type of liposomal liver-specific contrast medium was studied in an experimental tumour model. Rabbits were inoculated with VX2-carcinoma directly in the liver of laparotomy. CT studies were carried out 14 days after inoculation. The liver-specific contrast medium consisted of a suspension of liposomes in a 100 mg I/ml iodixanol solution, with equal amounts of encapsulated and nonencapsulated iodixanol. It was administered at a dose of 200 mg I/kg. The contrast of normal liver tissue to tumorous tissue was significantly increased by contrast medium administration, the increase being largest 10 min after injection.
PURPOSE: A new type of liposomal liver-specific contrast medium (CM) in CT was studied, and the results were compared with those obtained with Mn-DPDP, a paramagnetic hepatobiliary CM, in MR imaging. The contrasts of normal liver tissue to tumorous tissue and the importance of the CM for tumour detection in the 2 modalities were studied in a rabbit tumour model. CT and T1-weighted pre- and postcontrast and T2-weighted MR images precontrast were obtained. MATERIAL, METHODS AND RESULTS: Compared to precontrast images, significantly higher contrasts of normal liver tissue to tumorous tissue were obtained after CM administration in both CT and MR examinations. At radiologic evaluation, significantly more tumours were detected after CM administration in CT and in T1-weighted MR images than in precontrast images in CT and T1-weighted MR. There were no significant differences in tumour detection frequency in MR studies including a T2-weighted pulse sequence, postcontrast CT, or postcontrast T1-weighted MR imaging. CONCLUSION: The use of liver-specific CM improves visualization of liver tumours in CT and T1-weighted MR imaging.
MRI and CT are modalities appropriate for liver imaging. To obtain higher sensitivity in diagnoses of focal lesions in the liver, contrast media (CM) are used. Non-specific extracellular CM are not optimal as they rapidly diffuse into both normal tissue and tumorous tissue. By two different mechanisms, the hepatobiliary route and targeting to the reticuloendothelial system, agents may accumulate in normal liver tissue, thereby giving liver-specific CM. So far no such agents have been approved for clinical use. In the present studies, animal models were used to investigate the imaging efficacy of experimental liver-specific CM and answer the following questions: i) Do these new liver-specific CM result in enhancement of normal liver? ii) If enhancement in normal liver is present, does this result in higher contrast of normal liver to tumorous tissue? iii) If higher contrast of normal liver to tumorous tissue is present, does this result in higher tumour detection-rates? Relative to non-enhanced and contrast-enhanced CT, what tumour detection-rate is obtained using non-enhanced and contrast-enhanced MRI? All the liver-specific CM studies possessed the ability to significantly alter the signal in normal liver tissue. Compared to precontrast values, the liver-specific CM studied in MRI (Mn-DPDP) and CT (IEEC-particles and iodixanol-liposomes) were able to increase significantly the contrast of normal liver tissue to tumorous tissue and the tumour detection-frequency in VX2-carcinoma liver tumour-bearing rabbits. In CT using a non-specific extracellular CM, iohexol, no improvement in contrast or tumour detection-frequency was obtained. As reflected in the values of contrast-to-noise obtained, MRI and CT have the same potential for tumour detection in the liver model used in the present studies. Liver-specific CM have the property of improving the contrast of normal liver tissue to tumorous tissue in MRI and CT, giving higher tumour detection-rates. Permitting intravenous administration and the use of long imaging-windows, liver-specific CM are easy to use.
Laparoscopic cholecystectomy (LC) is attempted in all our patients scheduled for cholecystectomy. The related standard radiologic procedures are preoperative ultrasonography (US) and preoperative cholangiography (PCA). In a retrospective study of 214 patients scheduled for LC over a 2-year period we have reviewed the radiologic and clinical records. Preoperative US revealed stones in the common bile duct (CBD) in 8 patients, all treated with endoscopic papillotomy before or after operation. PCA was successful in 176 patients (82%) and gave crucial information in 22 patients including 8 with stones in the CBD not preoperatively diagnosed, 6 with anomalous anatomy, and 8 with malpositioned surgical clip on the cystic duct. In 26 patients LC was converted into open surgery, but in only one case due to CBD stone revealed at PCA. Seventeen patients had minor postoperative complications, all managed conservatively. We consider preoperative US and PCA appropriate radiologic investigations in conjunction with LC.
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.
RATIONALE AND OBJECTIVES: The authors compared the physiologic and nephrotoxic effects of the magnetic resonance imaging contrast medium gadopentetate with two conventional radiographic contrast media. METHODS: Rabbits were injected intravenously with one of the following solutions: 1) gadopentetate (0.1 M); 2) iohexol (300 mg I/mL); 3) metrizoate (300 mg I/mL); and 4) NaCl (0.9%). Blood samples were taken before and 5, 15, 45, 90, and 180 minutes after injection of the solutions and were analyzed for creatinine, aldosterone, and contrast media levels. Urine was sampled before and 1, 2.5, and 5 hours after injection of the solutions, and creatinine, leucine amino peptidase (LAP), alkaline phosphatase (ALP), gamma glutaryl transferase (GGT), and N-acetyl beta-D-glucosaminidase (NAG) activities were quantified. RESULTS: Contrast media clearance was similar for gadopentetate, iohexol, and metrizoate. Plasma aldosterone was significantly higher in the two groups injected with iodinated contrast agents compared with the gadopentetate and saline groups in the 3-hour samples. During the 5 hours after injection, the excretion of brushborder enzymes LAP, ALP, and gamma GT was significantly higher for all contrast media compared with pre-contrast values and 0.9% NaCl controls. NAG, a lysosomal enzyme from tubular cells, showed a significant increase compared with pre-contrast values for all contrast media. CONCLUSIONS: Intravenous injection of gadopentetate in rabbits showed nephrotoxicity of the same order as that of conventional iodinated contrast media.
A bowel labeling agent is important for improving abdominal MR. Besides providing contrast between the bowel and other organs, the contrast agent itself is a potential source of artifacts. The artifacts created by superparamagnetic particles (SPP) subjected to motion have been studied in vitro at 0.5 T, and compared to artifacts created by a paramagnetic compound. Apart from the expected static effects of the SPP, movement induced additional artifacts were seen as signal displacements in the phase-encoding direction. The artifacts were obvious at an iron concentration of 1 mg Fe/ml, barely visible at 0.2 mg Fe/ml, and completely absent at 0.1 mg Fe/ml. Artifacts were also evident with the SPP outside the imaging slice. This further emphasizes the importance of choosing the lowest effective dose when using SPP contrast agents. For the paramagnetic agent, motion propagated artifacts consisted of high and low signal regions in a mosaic pattern.
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A new particulate magnetic resonance (MR) contrast agent was prepared by controlled precipitation of iron oxide in an aqueous starch solution. The potential of the magnetic starch microspheres (MSM) as a hepatosplenic contrast enhancer was studied by MR spectroscopy and MR imaging. Intravascular administration of MSM to rodents showed an effective blood clearance and a tissue-specific localization of the substance. MSM doses in a range of 0.3-1.5 mg Fe/kg caused a 50% alteration in sensitive contrast parameters (ED50 doses) of liver and spleen. The contrast effect of MSM in liver and spleen was halved within 2 to 5 days. The approximated lethal MSM dose in mice was 150-200 mg Fe/kg. MSM is a tissue-specific MR contrast substance with high efficacy, rapid bioelimination, and low acute toxicity.
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The authors investigated in a rat model the efficacy of magnetic resonance imaging (MRI) contrast media for evaluating the liver in conditions of acute biliary obstruction. Two liver-specific MRI contrast media, Cr-DEHIDA and Mn-DPDP, and the nonspecific agent Gd-DTPA were studied in normal rats and in rats whose bile ducts had been ligated before administration of the contrast medium. Images were made using a 2.4 T animal MRI system, and intensity enhancement of liver after contrast medium injection was calculated. Metal analyses of serum and liver tissue and T1 and T2 measurements on liver samples in vitro were performed. The differences in image intensity enhancement of liver between normal rats and rats with ligated bile ducts were not significant for any of the three contrast media. Imaging with Mn-DPDP resulted in the highest intensity enhancement of the liver compared with Cr-DEHIDA and Gd-DTPA. Contrast media concentrations in liver tissue were not significantly different between normal rats and rats with ligated bile ducts; however, Cr-DEHIDA concentrations in serum were higher after bile duct ligation. In vitro measurements of liver tissue indicated unique relaxation properties for Mn-DPDP. This investigation indicates that the contrast media studied may be useful in situations where suspected liver pathology is complicated by acute biliary obstruction.
Antipyrine clearance and half-life, which are measures of the hepatic metabolic ability, were determined prior to anaesthesia in 14 surgical patients. The antipyrine results correlated neither with the highest serum fluoride concentrations nor with the fluoride excretion in urine following administration of enflurane. Enzyme induction may therefore have little influence on enflurane metabolism in man. Inorganic fluoride concentrations in serum and in excreted urine were determined following the exposure of a total of 21 surgical patients to measured doses of enflurane. In the group of 14 patients tested for metabolic ability, a mean dose of 0.4 end-tidal vol. % X h enflurane resulted in a mean peak serum fluoride concentration of 6.8 mumol/l (maximum 13.6 mumol/l) 2 h after enflurane exposure. In the material as a whole, the enflurane dose was positively correlated with both post-anaesthetic highest serum fluoride concentrations and the 24-h post-anaesthetic urine pH (P less than 0.01) as well as urinary volume and fluoride excretion in urine during that time. At a urinary pH below 5.0, the fluoride excretion was very low, while the highest excretions were associated with a urinary pH of about 7.0. Raising the patient's per- and post-anaesthetic urine pH and maintaining a good urinary output (which also tends to increase urine pH) may be enough to prevent accumulation of inorganic fluoride in the body following enflurane anaesthesia.
The efficacy of mild analgesics after 160 various superficial operations was studied by comparing intravenous lysine-acetylsalicylate (LAS) 1.8 g, Litalgin 4 ml (metamizole = dipyrone 2.0 g+ pitophenone 8.0 mg) or paracetamol 0.5 g to oxycodone 4 mg. At 15 min postdrug, oxycodone 4 mg had the best peak effect but this significant (P less than 0.05) difference to mild analgesics disappeared at 30 min, and thereafter all test analgesics showed an equally low effect. Two-thirds of the patients anaesthetized without peroperative analgesics needed pain relief when recovering from superficial surgery. The need for pain relief was lowest after varicose vein operations 40% of the patients as compared to about 70% after other types of superficial surgery. In 42% of the patients requiring pain relief, the test analgesics alone gave sufficient pain relief. The rest needed an additional 5 mg of oxycodone, on average, to be comfortable. The combined use of mild analgesics and oxycodone for adequate pain relief did not seem to reduce the postdrug sedation as compared to oxycodone alone. The results indicate that in traditional clinical dosages LAS, dipyrone or paracetamol can substitute about 5 mg oxycodone but offer sufficient analgesia only in about 40% of the patients recovering from superficial surgery.
The analgesic dose-effect relationship of nefopam was compared in a double-blind randomised trial with that of oxycodone in immediate postoperative pain. Nefopam 15 mg or oxycodone 4 mg was given every 10 min i.v. (maximum six times) to patients in pain after upper abdominal surgery until their wound pain (scored 0-3) disappeared. The mean pain intensity (PI), initially 2.2 in both groups, descreased by approximately the same extent for up to two doses in both groups (to 1.5 after nefopam 30 mg and to 1.1 after oxycodone 8 mg). Thereafter PI was significantly less in the oxycodone group and diminished almost linearily to 0.1 after the sixth dose (24 mg). In the nefopam group, the PI score fell to 1.1 after the fourth dose (60 mg). This seemed to be the "ceiling" effect since additional doses up to 90 mg did not result in greater pain relief. In the oxycodone group, only two patients (12%) needed maximal dosage (6 x 4 mg), one of them requiring 32 mg of oxycodone. In the nefopam group, 12 patients (75%) needed further pain relief after the maximal dosage (6 x 15 mg). In these patients, oxycodone (maximally 16 mg) gave satisfactory analgesia. Drowsiness and a decrease in the respiratory rate were the principal side-effects of oxycodone, whereas tachycardia, restlessness, sweating and nausea were more frequent after nefopam.
The local haemostatic and cardiovascular effects of ornithine-8-vasopressin (POR 8) 5.5 IU and adrenaline 350 microng were compared in middle ear operations in combined and methoxyflurane anaesthesia. The study was double-blind. Adrenaline had statistically significantly better haemostatic properties than POR 8 and the method of anaesthesia did not affect the difference between adrenaline and POR 8. With both methods of anaesthesia adrenaline increased systolic arterial pressure and pulse rate, and transiently increased and then decreased diastolic arterial pressure. In contrast to adrenaline, POR 8 markedly increased diastolic arterial pressure and decreased pulse rate. All the parameters studied, the vasoconstrictors, the methods of anaesthesia as well as the times of measuring statistically significantly affected the changes both in systolic and diastolic arterial pressures. Only the methods of anaesthesia markedly affected the changes in the pulse rate. Transient electrocardiographic changes occurred from 6% to 17% in different groups.