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Biomedical subjects

M A Kirchin

Publications and source records attributed to M A Kirchin.

At least 19 recordsLinked to original sources
PubMed2004

A comparison of Gd-BOPTA and Gd-DOTA for contrast-enhanced MRI of intracranial tumours.

A two-centre intra-individual crossover study was performed in 23 patients with suspected high-grade glioma or metastases to assess and compare the safety and enhancement characteristics of two different MRI contrast media (gadobenate dimeglumine, Gd-BOPTA and gadoterate meglumine, Gd-DOTA) at equivalent doses of 0.1 mmol/kg body weight. T1-weighted spin-echo (SE) and T2-weighted fast SE images were obtained before and T1-weighted images 0, 2, 4, 6, 8 and 15 min after injection. T1-weighted images with magnetisation transfer contrast were acquired 12 min after injection. Qualitative assessment by blinded, off-site readers (reader 1:19 patients; reader 2:21) and on-site investigators (23) revealed significant (P< or =0.005) overall preference for Gd-BOPTA over Gd-DOTA for contrast enhancement (Gd-BOPTA preferred in 18, 15 and 18 cases; Gd-DOTA in 0, 1 and 1 and no preference in 1, 5 and 4; off-site readers 1 and 2, and on-site investigators, respectively). A similar significant preference for Gd-BOPTA was expressed by off-site readers and on-site investigators for lesion-to-brain contrast, lesion delineation, internal lesion structure, and overall image preference. Quantitative assessment by off-site readers revealed significantly (p<0.05) greater lesion enhancement with Gd-BOPTA than with Gd-DOTA at all times from 2 min after injection.

Aged↗
PubMed2002

Magnetic resonance imaging of metastatic disease to the brain with gadobenate dimeglumine.

Seventy-four patients with one to eight proven intraaxial brain metastases received a total cumulative dose of 0.2 mmol/kg bodyweight gadobenate dimeglumine, administered as sequential injections of 0.05, 0.05 and 0.1 m mol/kg over a 20-min period. MR imaging was performed before the first administration (T2- and T1-weighted sequences) and after each injection of contrast agent (T1-weighted sequences only). Quantitative assessment of images revealed significant (P <0.01) dose-related increases in lesion-to-brain (L/B) ratio and percent enhancement of lesion signal intensity. Qualitative assessment by two independent, blinded assessors revealed additional lesions in 22%, 25% and 38% (assessor 1) and 29%, 32% and 34% (assessor 2) of patients after each cumulative dose when compared with combined T1- and T2-weighted pre-contrast images. Significantly more lesions (P < 0.01) were noted by both assessors after the first injection and by one assessor after each subsequent injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted in 12%, 16% and 28% of patients by assessor 1 following each dose and in 24%, 27% and 30% of patients by assessor 2. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced MRI. For patients with one lesion observed after an initial dose of 0.05 mmol/kg, additional lesions were noted by assessors 1 and 2 in 9.1% and 11.8% of patients, respectively, after a cumulative dose of 0.1 mmol/kg and in a further 9.1% and 5.9% of patients, respectively, after a cumulative dose of 0.2 mmol/kg. No safety concerns were apparent.

Brain Neoplasms↗
PubMed2001

Safety assessment of gadobenate dimeglumine (MultiHance): extended clinical experience from phase I studies to post-marketing surveillance.

Clinical trials completed by September 2000 on gadobenate dimeglumine (Gd-BOPTA; MultiHance) included 2540 adult and pediatric subjects that were administered this agent. For adult patient volunteers, the overall incidence of adverse events (AEs) was 19.8%, although marked study- and indication-related differences were apparent. Events potentially related to Gd-BOPTA administration were reported for 15.1% of adult patients. The vast majority of AEs were non-serious, mild, transient, and self-resolving. Headache, injection site reaction, nausea, taste perversion, and vasodilation were the most common AEs, reported with a frequency of between 1.0% and 2.6%. Serious AEs potentially related to Gd-BOPTA were reported for five (0.2%) patients overall. Controlled studies revealed no differences between Gd-BOPTA and other gadolinium chelates or placebo in the incidence and type of AEs. Similarly, no differences with respect to adult patients and/or comparator were noted in studies on pediatric subjects and subjects with renal or liver insufficiency. Post-marketing surveillance of approximately 100000 doses revealed an overall AE incidence of < 0.03% with serious AEs reported for < 0.005% of patients.

Adolescent↗
PubMed2001

Gadobenate dimeglumine-enhanced magnetic resonance imaging of intracranial metastases: effect of dose on lesion detection and delineation.

Seventy-four patients with one to eight proven intraaxial metastatic lesions to the brain received a total gadobenate dimeglumine dose of 0.3 mmol/kg of body weight, administered as three sequential bolus injections of 0.1 mmol/kg, at 10-minute intervals over a 20-minute period. Quantitative and qualitative assessments of efficacy were performed after each injection and a full evaluation of safety was conducted. Cumulative dosing produced significant (P < 0.01) dose-related increases in lesion-to-brain (L/B) ratio and lesion signal intensity (SI) enhancement. Two independent, blinded assessors noted additional lesions, compared to unenhanced images in 31% and 33%, 49% and 42%, and 50% and 48% of patients after each cumulative dose, respectively. Significantly more lesions were noted after the first injection, compared to unenhanced images (P = 0.002 and P < 0.001; assessors 1 and 2, respectively), and after a second injection, compared to the first (P < 0.001 and P = 0.039; assessors 1 and 2, respectively). Neither assessor noted significantly more lesions after the third injection. For patients with just one lesion observed on unenhanced T1- and T2-weighted images, additional lesions were noted by assessors 1 and 2 for 27% and 26%, 48% and 35%, and 42% and 41% of patients, respectively, following each injection. Contemporaneously, diagnostic confidence was increased and lesion conspicuity improved over unenhanced magnetic resonance imaging (MRI). For patients with one lesion observed after 0.1 mmol/kg of gadobenate dimeglumine, additional lesions were noted for 24% and 17% of patients (assessors 1 and 2, respectively) following a second 0.1 mmol/kg injection. Only assessor 2 noted additional lesions following the third 0.1 mmol/kg injection. The findings of on-site investigators concurred with those of the two off-site assessors. No safety concerns were apparent.

Brain↗
PubMed2001

Phase III, randomized, double-blind, cross-over comparison of gadoteridol and gadopentetate dimeglumine in magnetic resonance imaging of patients with intracranial lesions.

This study compares the efficacy and safety of gadoteridol with that of gadopentetate dimeglumine for enhanced MRI in subjects with intracranial lesions. A total of 92 subjects at three European centres underwent one MRI study enhanced with 0.1 mmol/kg gadoteridol and another with 0.1 mmol/kg gadopentetate dimeglumine. Contrast agents were assigned in random order, separated by 3-7 days. Eighty subjects were evaluated for efficacy. The presence of pathology, degree of enhancement, location and number of lesions, as well as additional information gained, were compared for each subject's unenhanced and enhanced scans for both the gadoteridol and gadopentetate dimeglumine examination. Safety was evaluated in all treated subjects by means of pre- and post-dose vital signs, laboratory tests and by monitoring for adverse events. There was no significant difference in the number of lesions visualized pre- and post-contrast for the two contrast agents. A high degree of correlation was noted between the two blinded readers. When post-contrast image sets were compared between contrast agents, there was no significant difference in superiority of one agent over the other for any of the evaluators (P > 0.05). No significant differences for any safety parameter were noted between the two agents. Gadoteridol and gadopentetate dimeglumine are effective and well tolerated for use in contrast-enhanced MRI of the CNS at a dose of 0.1 mmol/kg.

Adolescent↗
PubMed2001

Detection of intracranial metastases: a multicenter, intrapatient comparison of gadobenate dimeglumine-enhanced MRI with routinely used contrast agents at equal dosage.

RATIONALE AND OBJECTIVES: To compare gadobenate dimeglumine (MultiHance) with other commercially available MRI contrast agents for the detection of intracranial metastases. METHODS: A retrospective assessment was performed on MR images from 22 patients enrolled in a prior phase II clinical trial of gadobenate dimeglumine. Each patient underwent two examinations: a first examination with one of three "comparator" agents (gadopentetate dimeglumine, gadodiamide, and gadoterate meglumine) at a dosage of either 0.1 or 0.2 mmol/kg, and then a similar examination with gadobenate dimeglumine at equal dosage. All images were evaluated randomly for lesion number and location in unpaired and then paired fashion by two independent, masked neuroradiologists. A third assessor performed quantitative assessments on the available complete sets of digitally recorded images (10 cases). RESULTS: The findings for the comparator agents were pooled. Sensitivity for lesion detection with gadobenate dimeglumine (93%-100%) was markedly superior to that of comparator-enhanced examinations (65%-73%). The increase of lesion-to-brain contrast of the main lesion was consistently greater with gadobenate dimeglumine than with comparator agents relative to unenhanced contrast (+43% vs. +27%). CONCLUSIONS: Gadobenate dimeglumine proved to be a more efficacious agent than comparator contrast agents for the detection of intracranial metastatic lesions: superior efficacy was noted by both reviewers for total lesion count as well as for sensitivity and positive predictive value for lesion detection. The higher relaxivity of gadobenate dimeglumine might explain the superior sensitivity of gadobenate dimeglumine-enhanced MRI for the detection of central nervous system metastases.

Brain Neoplasms↗
PubMed2001

Iomeprol: current and future profile of a radiocontrast agent.

RATIONALE AND OBJECTIVES: To review the safety and efficacy profiles of iomeprol by examining the most indicative comparative clinical studies of iomeprol with widely used low-osmolar ionic or nonionic contrast agents, and to illustrate the recent development in iomeprol liposomal formulations for liver imaging and intravascular enhancement. METHODS: Randomized, double-blind, comparative studies were performed of iomeprol versus iopamidol, iopromide, ioxaglate, iopentol, iodixanol, ioversol, and iohexol. In all studies, safety controls included pre- and postadministration physical examinations, monitoring of vital signs, electrocardiography, clinical laboratory investigations, and 24- or 72-hour postadministration monitoring of patients for adverse events. Technically adequate images were rated for diagnostic efficacy by masked assessors. RESULTS: Iomeprol showed similar safety and diagnostic efficacy compared with the nonionic monomers iopamidol, iohexol, and ioversol, and no statistically significant differences were observed. No differences in diagnostic efficacy between iomeprol and iopromide were observed, but in one study on 1,200 patients, the incidence of adverse events and adverse reactions was significantly higher with iopromide than with iomeprol. Iomeprol caused significantly less heat/pain than iopentol in one study; it showed similar safety and tolerability to the nonionic dimer iodixanol, the two agents causing no or modest, superimposable pain and heat sensation at injection and showing similar renal tolerability after intra-arterial injection. A comparison of iomeprol versus ionic dimer ioxaglate in 2,000 patients undergoing percutaneous coronary interventions showed that the incidence of thrombus-related events was similar with the two agents, but ioxaglate caused a significantly higher incidence of allergy-like reactions. First results with iomeprol-containing liposomal formulations show that these agents may facilitate the CT assessment of intrahepatic malignancies and CT angiography procedures. CONCLUSIONS: The overall results of numerous randomized, double-blind, comparative clinical studies in a variety of indications show that the diagnostic efficacy of iomeprol solutions does not differ significantly from that of the low-osmolar contrast media available on the marketplace when similar iodine strengths are used, although iomeprol may have better tolerability and safety than the ionic dimer and some of the nonionic monomers in selective applications. First results obtained with iomeprol-containing liposomal formulations are promising and may foster additional clinical testing.

Animals↗
PubMed2001

Focal nodular hyperplasia: morphologic and functional information from MR imaging with gadobenate dimeglumine.

PURPOSE: To determine whether gadobenate dimeglumine (Gd-BOPTA) is able to provide morphologic and functional information for characterization of focal nodular hyperplasia (FNH). MATERIALS AND METHODS: Sixty-three consecutive patients with proved FNH were retrospectively examined. Magnetic resonance (MR) imaging with T2-weighted turbo spin-echo and T1-weighted gradient-echo sequences was performed. Images were acquired prior to and during the dynamic phase of contrast-material enhancement and 1-3 hours after administration of 0.1 mmol/kg Gd-BOPTA. Qualitative analysis of signal intensity and homogeneity on images in the various phases of the MR study and examination for the presence of central scar or atypical features were performed. On the basis of features observed in the precontrast and dynamic phases, lesions were defined as typical or atypical. Intensity and enhancement patterns of the lesions and scars were also evaluated in the delayed phase. RESULTS: One hundred FNHs were depicted on MR images. Seventy-nine of 100 lesions demonstrated typical morphologic and enhancement characteristics. On delayed phase images, 72% of 100 FNHs appeared hyperintense; 21%, isointense; and 7%, slightly hypointense. The delayed pattern of enhancement was homogeneous, heterogeneous, and peripheral in 58%, 22%, and 20% of 100 FNHs, respectively. Atypical morphologic features and lesion and/or scar enhancement were observed in 21 of 100 FNHs. On delayed phase images, 76% of 100 atypical FNHs appeared hyperintense, 14% isointense, and 10% slightly hypointense. Hyperintensity and isointensity allowed the correct characterization in 90% of atypical FNHs. CONCLUSION: Gd-BOPTA during both dynamic and delayed phases provides morphologic and functional information for the characterization of FNH.

Adolescent↗
PubMed2000

Hepatocellular carcinoma: correlation between gadobenate dimeglumine-enhanced MRI and pathologic findings.

RATIONALE AND OBJECTIVES: To correlate the appearance of hepatocellular carcinoma on delayed (60 minutes) postcontrast T1-weighted gradient echo images with the mode of action of gadobenate dimeglumine (Gd-BOPTA) and the anatomic and pathologic characteristics of the lesions. METHODS: A total of 34 patients with hepatocellular carcinoma and varying degrees of diffuse liver disease were studied. T2-weighted spin echo and T1-weighted spin echo and gradient echo images were acquired before and 60 minutes after the intravenous administration of 0.1 mmol/kg Gd-BOPTA. Qualitative and quantitative evaluations of the images were performed and correlated with histologic findings. The quantitative evaluation, performed on T1-weighted gradient echo images, looked at the percentage increase of liver enhancement after Gd-BOPTA administration, the lesion-to-liver contrast/noise (C/N) ratio before and after Gd-BOPTA administration, and the C/N variation after Gd-BOPTA administration. Qualitative assessment considered the morphologic features of the lesions as well as the visual variation of contrast before and after Gd-BOPTA administration. Finally, a histologic evaluation was made of the degree of differentiation of the lesions and of the presence of fatty metaplasia, necrosis, bile, or intratumoral peliosis. RESULTS: Among the parameters affecting lesion identification were the extent of liver function, degree of vascularization, residual functionality of the tumor cells, and characteristics of the neoplastic tissue. Positive correlations (Spearman coefficients = 0.359 and 0.393, respectively) were observed precontrast between the degree of liver failure and the amount of contrast noise, and postcontrast between the amount of intralesional fatty metaplasia and the extent to which lesion conspicuity worsened after Gd-BOPTA administration. An inverse correlation (Spearman coefficient = -0.330) was observed between the degree of lesion differentiation and the visible appearance after Gd-BOPTA administration, with well-differentiated lesions tending toward worsened conspicuity postcontrast. A statistically significant difference (P = 0.001) was observed in the mean precontrast C/N ratio for lesions later showing unchanged conspicuity and worse conspicuity on postcontrast images, respectively. Marked variation (P = 0.019) was also observed between Child A and B cirrhotic patients for the degree of hepatic enhancement on postcontrast images. CONCLUSIONS: The results suggest that liver parenchyma signal intensity is influenced by the extent to which liver function is compromised, that residual hepatocytic functionality permits Gd-BOPTA uptake by certain lesions and that this uptake might subsequently impair the observed C/N ratio on delayed images, and that the worsening of lesion conspicuity on postcontrast images is influenced also by high quantities of intralesional fatty metaplasia.

Carcinoma, Hepatocellular↗
PubMed2000

Focal liver lesions: evaluation of the efficacy of gadobenate dimeglumine in MR imaging--a multicenter phase III clinical study.

PURPOSE: To evaluate gadobenate dimeglumine (Gd-BOPTA) for dynamic and delayed magnetic resonance (MR) imaging of focal liver lesions. MATERIALS AND METHODS: In 126 of 214 patients, MR imaging was performed before Gd-BOPTA administration, immediately after bolus administration of a 0.05- mmol/kg dose of Gd-BOPTA, and 60-120 minutes after an additional intravenously infused 0.05-mmol/kg dose. In 88 patients, imaging was performed before and 60-120 minutes after a single, intravenously infused 0.1-mmol/kg dose. T1- and T2-weighted spin-echo and T1-weighted gradient-echo images were acquired. On-site and blinded off-site reviewers prospectively evaluated all images. Intraoperative ultrasonography, computed tomography (CT) during arterial portography, and/or CT with iodized oil served as the reference methods in 110 patients. RESULTS: Significantly more lesions were detected on combined pre- and postcontrast images compared with on precontrast images alone (P <. 01). All reviewers reported a decreased mean size of the smallest detected lesion and improved lesion conspicuity on postcontrast images. All on-site reviewers and two off-site reviewers reported increased overall diagnostic confidence (P <.01). Additional lesion characterization information was provided on up to 109 (59%) of 184 delayed images and for up to 50 (42%) of 118 patients in whom dynamic images were assessed. Gd-BOPTA would have helped change the diagnosis in 99 (47%) of 209 cases and affected patient treatment in 408 (23%) of 209 cases. CONCLUSION: Gd-BOPTA increases liver lesion conspicuity and detectability and aids in the characterization of lesions.

Adult↗
PubMed2000

Evaluation of the accuracy of gadobenate dimeglumine-enhanced MR imaging in the detection and characterization of focal liver lesions.

OBJECTIVE: We evaluated the extent to which hepatic lesion characterization and detection is improved by using gadobenate dimeglumine for enhancement of MR images. MATERIALS AND METHODS: Eighty-six patients were imaged before gadobenate dimeglumine administration, immediately after the 2 mL/sec bolus administration of a 0.05 mmol/kg dose (dynamic imaging), and at 60-120 min after the IV infusion at 10 mL/min of a further 0.05 nmol/kg dose (delayed imaging). The accuracy for lesion characterization was assessed for a total of 107 lesions. Sensitivity for lesion detection was assessed for a total of 149 lesions detected on either intra-operative sonography, iodized oil CT, CT during arterial portography, or follow-up contrast-enhanced CT as the gold standard. RESULTS: The accuracy in differentiating benign from malignant liver lesions increased from 75% and 82% (the findings of two observers) on unenhanced images alone, to 89% and 80% on dynamic images alone (p<0.001, p = 0.8), and to 90.7% when combining the unenhanced and dynamic image sets (p<0.001, p = 0.023). Delayed images did not further improve accuracy (90% and 91%; p = 0.002, p< 0.05). A similar trend was apparent in terms of accuracy for specific diagnosis: values ranged from 49% and 62% on unenhanced images alone, to 76% and 70% on combined unenhanced and dynamic images (p<0.001, p = 0.06), and to 75% and 70% on inclusion of delayed images (p<0.001, p = 0.12). The sensitivity for lesion detection increased from 77% and 81% on unenhanced images alone, to 87% and 85% on combined unenhanced and dynamic images (p = 0.001, p = 0.267), and to 92% and 89% when all images were considered (p<0.001, p = 0.01). CONCLUSION: Contrast-enhanced dynamic MR imaging with gadobenate dimeglumine significantly increases sensitivity and accuracy over unenhanced imaging for the characterization of focal hepatic lesions, and delayed MR imaging contributes to the improved detection of lesions.

Adult↗
PubMed1999

MultiHance in the assessment of intracranial tumors: results of phase II clinical studies.

PURPOSE: To assess preliminarily the efficacy of 0.1 and 0.2 mmol/kg doses of MultiHance for contrast-enhanced magnetic resonance imaging of brain tumors. METHODS: Patients were imaged pre-dose using proton density (PD), T2-weighted and T1-weighted spin-echo sequences, and post-dose by repetition of the T1-weighted sequences at 0-15, 15-30, 30-45 and 45-60 min after the completion of MultiHance administration. Qualitative efficacy assessments of the image sets were performed by two blinded neuroradiologists in terms of the level of diagnostic information, the type of additional information provided by post-contrast images, the best post-contrast image set in terms of diagnostic information, the radiological utility of MultiHance, and the detectability of brain metastases. Extensive safety and tolerability controls were performed at 3 and 24 h post-contrast. RESULTS: Additional diagnostic information was available on MultiHance-enhanced images as compared to pre-contrast images for 58.678.9% of patients administered 0.1 mmol/kg MultiHance and 66.1-74.6% of patients administered 0.2 mmol/kg MultiHance. Generally, the early (0 to 30 min) post-contrast image sets were preferred, with a clear superiority at the 15-30 min post-dose time point. In a subgroup of 21 patients with brain metastases, a higher number of lesions was detected in 55.6-66.7% of the cases with 0.1 mmol/kg MultiHance and in 58.3% of the cases with 0.2 mmol/kg MultiHance. Overall, the usefulness of MultiHance was judged as good to excellent in 91.4% of the patients at both dose levels. A total of 12 of 120 patients (10%) reported 15 transient, self-resolving adverse events of mild-to-moderate intensity. No difference between doses was observed in the incidence of adverse events and no laboratory, ECG or vital signs abnormalities were reported. CONCLUSION: MultiHance is a safe and effective contrast agent for magnetic resonance assessment of brain tumors when administered intravenously at doses up to 0.2 mmol/kg.

Adult↗
PubMed1997

Trends and developments in MRI contrast agent research.

The currently prevailing trends in industrial contrast agent research for MRI are discussed. Specific mention is made of contrast agents for liver imaging using both static and delayed procedures, of the potential for blood pool agents and the form such agents may take, and of the ultimate challenge for contrast agent R&D: tissue-targeting in a wider sense to both normal and pathologic tissues.

Animals↗
PubMed1996

Production of reactive oxygen species by hemocytes from the marine mussel, Mytilus edulis: lysosomal localization and effect of xenobiotics.

Hemolymph of M. Edulis is rich in phagocytic hemocytes. Hemocytes contain numerous lysosomes which, in turn, contain various hydrolytic enzymes. Phagocytic activity of M. edulis hemocytes is thought to be associated with NAD(P)H-oxidase activity of the plasma membrane. The laser dye, dihydrorhodamine 123 (DHR), was used for cytochemical and biochemical detection of the generation of reactive oxygen species (ROS) by isolated M. edulis hemocytes. Hemocytes readily take up DHR from the suspension medium and selectively concentrate it in the lysosomes, wherein DHR is oxidized to fluorescent rhodamine 123. Concomitant uptake of DHR with superoxide dismutase or the spin-trap, tert-phenylbutyl nitrone, but not catalase markedly reduced fluorescence in the lysosomes implicating superoxide anion (O2-) but not hydrogen peroxide (H2O2) in DHR oxidation. Uptake of the anthraquinone, purpurin, and FeEDTA with DHR greatly amplified fluorescence within the lysosomes. These data are consistent with uptake of xenobiotics by hemocytes and their concentration in lysosomes wherein, ROS are generated in response to their accumulation. The rate of DHR oxidation by hemocytes was not stimulated by zymosan, a known stimulator of the oxidative burst. In vitro studies using the xanthine oxidase/hypoxanthine reaction to generate O2- and selective inhibitors of ROS production indicated that DHR is oxidized by O2- and H2O2 but not by .OH and that iron can participate in the reaction. Incubating isolated hemocytes promoted low-level, SOD-sensitive, FeEDTA-stimulated production of ethylene from alpha-keto-gamma-methiolbutyric acid, indicating the in situ formation of .OH via production of O2-. The above suggest that enhanced production of ROS in M. edulis hemocytes by xenobiotic accumulation within the lysosomal compartment should be considered in the toxic sequelae of exposure of marine molluscs to chemical pollutants.

Animals↗
PubMed1995

Effects of iodinated contrast media on pulmonary airway resistance in anesthetized guinea pigs.

RATIONALE AND OBJECTIVES: Bronchospasm is occasionally observed following iodinated X-ray contrast medium administration. We performed an in vivo study in guinea pigs to investigate the effects of a number of iodinated contrast media on pulmonary airway resistance and the mechanisms underlying the potential bronchoconstrictor effect. METHODS: The contrast media studied were the pharmaceutical formulations of iomeprol (400 mg I/ml), iopamidol (370 mg I/ml), and iohexol (350 mg I/ml), which are nonionic, triiodinated contrast media; diatrizoate (370 mg I/ml), an ionic, triiodinated contrast medium; iotrolan (300 mg I/ml), a nonionic, hexaiodinated contrast medium; and iocarmate (280 mg I/ml) and ioxaglate (320 mg I/ml), which are both hexaiodinated and ionic contrast media. Each contrast medium was administered intravenously at 2 g I/kg. Changes in pulmonary airway resistance were evaluated by measuring intratracheal pressure at the moment of maximum insufflation, or maximal insufflation pressure (MIP), in anesthetized guinea pigs submitted to forced ventilation. RESULTS: All contrast media except ioxaglate caused mean increases of MIP of no more than 20%. By contrast, ioxaglate caused a marked bronchoconstrictor effect, increasing MIP by 242% +/- 46%. Of the drugs tested for antagonistic action on this increase in MIP, salbutamol inhibited almost completely the increase in MIP for the first 40 min posttreatment. Similarly, lysine acetylsalicylate and indomethacin consistently reduced MIP after contrast media administration to levels only 30% and 14% above those of baseline precontrast media, respectively. Promethazine had only a minor inhibitory effect, and the response to prednisolone varied. CONCLUSION: There was no apparent relationship between the size of the increase in airway resistance and the charge or molecular weight of the contrast agent molecule or the pharmaceutical formulation. The increase induced by ioxaglate must be attributed to inherent molecular toxicity mediated through a direct action on the production of bradykinin and/or the prostanoid products of the cyclooxygenase pathway, rather than through a direct action on the release of histamine.

Airway Resistance↗
PubMed1989

Cytochrome P-450 and oxidative metabolism in molluscs.

1. Cytochrome P-450 and the associated components and oxidative activities of a mixed-function oxidase (MFO) system are localized primarily in the microsomes of the digestive gland of molluscs. 2. Cytochrome P-450 and putative cytochrome P-450-catalysed oxidative activities, measured in vitro and/or in vivo, have variously been detected in 23 species of mollusc. 3. Cytochrome P-450 and other MFO components and activities may be increased by exposure to xenobiotics, but the results are variable and no correlation is obvious between changes in cytochrome P-450 content and measured MFO activities (benzo[a]pyrene hydroxylase (BPH) and 7-ethoxycoumarin O-deethylase (ECOD)). 4. Type II binding compounds (clotrimazole, miconazole, ketoconazole, metyrapone and pyridine) give type II difference spectra with mussel digestive gland microsomal P-450, whereas type I binding compounds (testosterone, 7-ethoxycoumarin, alpha-naphthoflavone, SKF525-A) give apparent reverse type I difference spectra. 5. The existence of multiple or particular forms (P450 IVA or LAw) of cytochrome P-450 is indicated from enzyme kinetics and inhibition studies, seasonality, purification studies and cDNA probes. 6. Microsomal MFO activities are observed even in the absence of added or generated NADPH, and the NADPH-independent BPH, ECOD and N,N-dimethylaniline N-demethylase activities are inhibited by reducing agents, including NADPH. 7. The major metabolites of microsomal benzo[a]pyrene metabolism are quinones. 8. One-electron oxidation is considered to be one possible mechanism of molluscan cytochrome P-450 catalytic action.

Animals↗