Molecular cloning and functional expression of a recombinant 72.5 kDa fragment of the 110 kDa regulatory subunit of smooth muscle protein phosphatase 1M

RATIONALE AND OBJECTIVES: We compared adverse reactions and image quality for hysterosalpingography (HSG) performed with ionic (diatrizoate meglumine combined with iodipamide meglumine [DM + IM]) and nonionic (iohexol) contrast media. METHODS: We performed a study of 95 patients who had HSG and were randomly selected to receive DM + IM or iohexol. Patients reported episodes of abdominal pain and other adverse reactions immediately and 24 hr after the procedure and categorized severity of symptoms on a subjective scale. Two radiologists evaluated image quality for diagnosis. RESULTS: Prevalence of abdominal pain and other reactions both immediately and 24 hr after HSG was lower in patients who received iohexol than in patients who received DM + IM. Moderate or severe abdominal pain was significantly lower in the iohexol group than in the DM + IM group (p < .05). Visualization of the uterine cavity and ampullary rugae was judged excellent with both contrast media (87% with iohexol and 92% with DM + IM). CONCLUSION: Iohexol and DM + IM are excellent contrast media for use during HSG; iohexol 300 may cause fewer episodes of more severe and prolonged abdominal pain.     

Head pain associated with sixth-nerve palsy: spontaneous dissection of the internal carotid artery

BACKGROUND: Iodixanol (Visipaque, Nycomed Imaging AS, Oslo, Norway) is a new non-ionic and isotonic X-ray contrast medium. OBJECTIVE: To assess its safety and efficacy for paediatric excretory urography. MATERIALS AND METHODS: A three-centre trial in which 72 patients were randomised into three parallel groups: iodixanol 270 mgI/ml, iodixanol 320 mgI/ml and iohexol 300 mgI/ml (Omnipaque, Nycomed Imaging, Oslo, Norway). Doses ranging from 1 to 3 ml/kg never exceeded 50 ml. Pulse rate and blood pressure were recorded before, during, and after the examination. Adverse events, including injection associated discomfort, were recorded during and up to 24 h after the examination. The diagnostic quality of the urograms was assessed on a four-level scale. RESULTS: No serious adverse event occurred in any of the three groups. One patient who was given iodixanol 270 mgI/ml, three who received iodixanol 320 mgI/ml, and one who received iohexol 300 mgI/ml experienced transient adverse events. More than 80 % of the urograms in all three groups were rated "good" or "excellent". CONCLUSION: Iodixanol, either 270 mgI/ml or 320 mgI/ml, is well tolerated and efficacious for excretory urography in children.     

Safety and efficacy of contrast-enhanced MRI in the brain, head and neck: gadodiamide injection versus gadopentate dimeglumine

The objective of the present study was to evaluate the safety and efficacy of gadodiamide injection, a non ionic MRI contrast medium in comparison with the ionic agent gadopentate dimeglumine. Two groups of 50 patients with known or suspected lesions of the brain or head and neck were enrolled in a double -blind, randomised trial. In the gadopentate dimeglumine group three patients reported four adverse events, and in the gadodiamide injection group, four patients reported four side effects. All events were minor. Two radiologists analyzed pre and post-contrast MR images. The parameters evaluated were the number of lesions, delineation of the lesion, gain of diagnostic information, and final diagnosis. Both contrast media gave identical diagnostic information.     

Adverse events and cost savings three years after implementation of guidelines for outpatient contrast-agent use

The ability of guidelines limiting the use of low-osmolality contrast media (LOCM) to save money without jeopardizing patient care was studies. In February 1993 an academic medical center implemented guidelines to reduce the use of LOCM for outpatient computed tomography and excretory urography; the guidelines limited LOCM to patients at high risk of adverse reactions to contrast agents. Data on contrast media received and frequency of adverse events were compiled from billing sheets and incident reports for March 1993 through February 1996. The number of patients receiving LOCM over the three years was 1325, and the number receiving high-osmolality contrast media (HOCM) was 4435. Of the HOCM recipients, 165 (3.7%) had adverse reactions; 0.4% of these reactions were major, 3.1% were minor, and 0.2% were extravasations. Among LOCM-treated patients, 35 (2.7%) had adverse reactions; 0.5% were major, 1.7% were minor, and 0.5% were extravasations. The only significant difference in adverse effects between the groups was in the frequency of minor reactions. The costs of HOCM and LOCM over the three years were $54,660 and $152,523, respectively. Had 90% of the 5760 patients received LOCM, the total cost of contrast agents would have been $603,723; thus, the estimated drug cost saving was $396,540, or $132,180 annually. With costs of treating adverse events factored in, the net annual cost saving was $132,093. Guidelines limiting the use of LOCM to high-risk patients saved an academic medical center an estimated $132,093 annually in drug costs for specific outpatient imaging procedures, without adversely affecting patient care.     

Myelography in the dog with non-ionic contrast media at different iodine concentrations

Image quality and side effects were evaluated retrospectively in a series of 183 myelographic studies performed with two non-ionic contrast media (iohexol and iopamidol) at different concentrations. Side effects during and following the procedure were recorded. Image quality was assessed using an arbitrary scoring system and statistical analysis was performed with the cross-tabulation test (4 x 2 table) by comparing two groups receiving contrast medium at higher and lower concentrations. No significant differences in side effects were observed between the two groups but the ratings for image quality were significantly higher in the group receiving contrast medium at the higher concentration than in the group receiving the lower concentration. The results suggest that a high concentration of non-ionic contrast media can safely be used in dogs and may improve image quality.     

Malignant hyperthermia and neuroleptic malignant syndrome in a patient during treatment for acute asthma

PURPOSE: The safety and diagnostic efficacy of iodixanol (Visipaque) 270 mg I/ml was compared to that of iopamidol (Iopamiron) 300 mg I/ml in knee arthrography. MATERIAL AND METHODS: This trial was a bi-center double-blind trial including 128 patients (iodixanol/iopamidol 64/64 patients). Efficacy was evaluated by blinded grading of the diagnostic quality of the p.a. images taken 0, 12 and 25 min after contrast administration by the examining radiologist and later at a consensus evaluation by two experienced skeletal radiologists. Adverse events were recorded. RESULTS: No patient experienced any adverse event. The proportion of better images at both 12 and 25 min after injection was higher in the iodixanol group compared to the iopamidol group both by the examining radiologist and at the consensus evaluation. CONCLUSION: In the knee joint iodixanol is a safe contrast medium. The contrast effect of iodixanol lasted longer than that of iopamidol, which can be important when performing arthrography, especially CT arthrography, where the time between puncture and examination can be prolonged.     

Contrast medium studies of the venous system

PURPOSE: To give an overview of various diagnostic techniques and indications for phlebography in different parts of the body. METHODS: Procedures of conventional phlebography of the lower and upper extremity and cavography are described and their indications in comparison to alternative techniques are discussed. The literature is reviewed with regard to specific advantages and disadvantages of the different methods. RESULTS: Conventional phlebography with iodine contrast media is still considered to be the gold standard in many regards. The diagnosis of acute and chronic thrombotic disease, venous vascular occlusions, hemodynamic malfunctions and anatomic variants of the venous system can readily be established with contrast phlebography. DISCUSSION: Main disadvantages of contrast studies of the venous system are radiation exposure and adverse effects of contrast media. Non-invasive methods such as ultrasound and MR-phlebography are becoming more and more popular and may replace venography. Other techniques such as CT-phlebography and the use of CO2 as contrast medium are under investigation. The latter can be indicated in the case of contraindications against iodine contrast media. CONCLUSION: When choosing diagnostic methods for the venous system, their sensitivity and specificity for specific diagnoses and vascular territories have to be balanced against the risks and disadvantages.     

Adverse effects of a new non-ionic contrast medium in heart catheterization

Tolerance of a New Non-ionic Contrast Medium during Heart Catheterization The new non-ionic contrast medium iomeprol (CAS 78649-41-9) was investigated for adverse reactions and diagnostic quality in 75 patients undergoing heart catheterization. Blood pressure and ECG were continuously registered. The patients were asked for subjective complaints by using a standardized questionnaire. Experienced cardiologists assessed the diagnostic quality of the angiograms. With iomeprol neither fatal nor severe reactions were observed. The dye had only little influence on diastolic and systolic blood pressure; heart rate was not significantly influenced. Minor and partly moderate adverse reactions all being completely reversible were observed in 14 patients (18.7%). One patient complained of strong heat sensation after dye injection into the left ventricle. The diagnostic quality of the angiograms allowed to make a definitive diagnosis in all cases. Thus, iomeprol proved to be a suitable and safe contrast medium for heart catheterization.     

Hysterosalpingo contrast sonography (HyCoSy) with SH U 454 (Echovist) for the assessment of tubal patency

A total of 88 Fallopian tubes from 44 patients was examined with hysterosalpingo contrast sonography (HyCoSy), hysterosalpingogram (HSG), and laparoscopic chromopertubation (LC) in order to assess their relative accuracy for measuring tubal patency. HyCoSy was done by transvaginal ultrasound and the contrast was SH U 454 (Echovist). The flow of multiple fractions of the contrast medium through each Fallopian tube was observed in real time in appropriate imaging planes by means of a transvaginal probe. Compared with laparoscopic results, we found a sensitivity of 85.2%, a specificity of 85.2%, a positive predictive value (PPV) of 71.9%, a negative predictive value (NPV) of 92.9% and concordance (HyCoSy/LC) of 85.2%, while the corresponding values for HSG were sensitivity = 85.2%, specificity = 83.6%, PPV = 69.7%, NPV = 92.7% and concordance (HSG/LC) of 84.1%. Compared with HSG results, HyCoSy obtained a co-positivity of 66.7%, a co-negativity of 81.8% and a concordance of 76.1%. In conclusion, HyCoSy with SH U 454 proved to be a reliable and safe modality for evaluating tubal patency; it is suitable as an outpatient diagnostic procedure to be used before more invasive procedures.     

Rate of neuronal fallout in a transsynaptic cerebellar model

PURPOSE: A retrospective study was undertaken of the late adverse reactions following the injection of contrast media. The purpose was to determine whether there was a difference between non-ionic monomeric (iohexol) and non-ionic dimeric (iodixanol) contrast media in the reactions produced. MATERIAL AND METHODS: A total of 3,408 patients were sent a written questionnaire in which they were asked to confirm or deny any subjective discomfort or adverse event during a period of one hour to one week after a previous radiological examination with contrast medium. Patients who had undergone angiography (i.v. or i.a. injection) and CT (i.v. injection) were included. Objective signs of an allergy-like reaction were listed and the patients were asked to subjectively quantify any consequent discomfort. RESULTS: The compliance rate was 84%. Of the 3075 injections finally included in the study, 133 (4.3%) had resulted in contrast-medium-related adverse reactions of which 72 (2.3%) were immediate and 61 (2%) were late. Iohexol induced late reactions in 14/851 (1.7%) cases, and iodixanol in 24/1218 (2.0%) cases following i.v. injection and in 23/1006 (2.3%) cases following i.a. injection. The differences were not significant. There were no differences between the two contrast media in the subjective rating of discomfort except that the patients who had received iodixanol also had the highest individual-intensity score. No patient had been hospitalized owing to an adverse reaction and all reactions had been regarded as mild or moderate. CONCLUSION: The number of late adverse reactions was low. There was no difference in the frequency of the late adverse reactions following i.v. injection between iodixanol and iohexol. There was also no difference in the reactions between the i.a. and i.v. injections of iodixanol.     

Adverse political events and psychological adjustment: two cross-cultural studies

OBJECTIVE: The life events model was extended to the political arena to enable the comparison of children's adjustment reactions to political stress. The cross-cultural impact of adverse political events on psychological adjustment was examined for two closely matched research samples, Arab and Jewish children and Palestinian and Israeli children. METHOD: All children completed the Political Life Events scale and the Brief Symptom Inventory in their home languages. RESULTS: The hypothesis of a linear relation between adverse events and psychological distress was not confirmed in both studies. In study 1, a direct relation emerged for both Jewish and Arab Israeli children. However, in study 2, when separated by nationality, results revealed opposite trends for each nation. For Israelis there was a linear relation, but for Palestinians there was a consistent inverse relation between increased severity of political life events exposure and distress, both for the global index and for specific symptomatology. CONCLUSION: It is proposed that these cross-cultural results stem from differential mediating coping mechanisms, specifically passive versus active strategies, which intervene between the stressor-adjustment link. The need to address short- and long-term consequences of political stress on children's mental health is discussed.     

Angiography during interventional procedures with carbon dioxide (CO2) (carbo-angiography) in patients with increased contrast media risk

Within the last 18 months we examined 130 patients with known complications or contraindications using iodinated contrast media for angiography by using carbon dioxide as contrast agent in digital subtraction angiography technique. These were diagnostic pelvis-leg angiographies (n = 106) with simultaneous consecutive interventional radiologic therapy in 68 cases. In 19 dialysis access fistulas 11 angioplasties were performed in the same session. In 5 cases of renal allografts no interventional radiologic therapy was necessary. For CO2 application an electronic controlled special injector was used. Carbon dioxide has a number of advantages: no adverse reactions, nonallergenic and can be used several times without increasing risks and is cost-saving. CO2 angiography is a sensitive method, for detection vessel wall processes below the diaphragm. It can replace conventional angiography.     

Improved risk stratification in unstable angina: identification of patients at low risk for in-hospital cardiac events by admission echocardiography

BACKGROUND: Current protocols for risk stratification of patients with acute chest pain syndromes rely on clinical parameters and are oriented toward identification of patients at high risk for adverse cardiac events; however, this paradigm for risk stratification does not adequately address the observation that adverse cardiac events are relatively uncommon in this population. In an era of cost containment, consideration also should be given to identification of patients at low risk for adverse cardiac events, who may be safely discharged without expensive inpatient hospitalization. HYPOTHESIS: The purpose of this study was to develop echocardiographic predictors that identify unstable angina patients at low risk for adverse cardiac events and that discriminate between low- and high-risk patients. METHODS: The predictive accuracy of retrospectively determined echocardiographic predictors were compared in a population-based sample of 66 consecutive unstable angina patients undergoing echocardiography within 24 h of admission. RESULTS: Echocardiographic predictors of adverse events included wall motion score index > or = 0.2, ejection fraction < or = 40%, and mitral regurgitation severity > 2. One or more echocardiographic predictors of adverse events were present in 32 patients (48%). A composite echocardiographic predictor of adverse events was specific, had a high positive predictive value for the identification of high-risk patients, and discriminated between unstable angina patients at high and low risk for adverse cardiac events. CONCLUSION: Echocardiographic predictors of adverse events are specific and discriminate between unstable angina patients at high and low risk for adverse cardiac events.     

Adverse events after endoluminal repair of abdominal aortic aneurysms: a comparison during two successive periods of time

PURPOSE: The aim of this study was to document the incidence rate of adverse events after endoluminal repair of abdominal aortic aneurysms (AAAs) during two successive periods of time. METHODS: One hundred ninety patients (175 men, 15 women; mean age, 72 years) underwent endoluminal repair of AAAs in a 5(1/2)-year period. Adverse events were documented prospectively for all the patients throughout this interval. An adverse event was defined as any of the following events: a death within 30 days, a conversion to open repair, the need for further intervention (either open or endovascular), the need for hemodialysis, a failure to cure the AAA, and wound complications. The patients were divided into two groups those who underwent operation in the initial 3-year period (group I; n = 75) and those who underwent operation in the subsequent 2(1/2)-year period (group II; n = 115). The results were analyzed for total adverse events for both periods of time and for difference in incidence rates within categories of adverse events between the two groups. RESULTS: Eight patients (4.2%) died in the perioperative period. The endoluminal repair failed in 17 patients (8.9%), which necessitated a primary conversion to open repair at the original operation. In 88 patients, 110 adverse events occurred. There was no significant difference in the incidence rates of adverse events in patients in group I (37/75) and group II (51/115). Apart from primary conversion (P =.007), there was no significant difference in the incidence rates of adverse events between group I and group II within the following categories: perioperative (within 30 days) deaths, primary conversion, secondary conversion, supplementary endoluminal repair, intervention for lower limb ischemia, hemodialysis necessitated, failure to cure the AAA as a result of persistent endoleak, and wound complications. CONCLUSION: Despite improvements in technology and increasing experience, adverse events continue to occur in a relatively high proportion of patients (45%) who undergo endoluminal repair of AAA. Reporting the incidence rates of adverse events provides a more accurate picture of the morbidity rates of the endoluminal method rather than simply listing the procedures as successes or failures. The similarity in the incidence rates of adverse events in patients in group I and group II suggests that there are inherent risks in the endoluminal method rather than iatrogenic complications that occur during the learning curve with a new technique.     

Effect of molecular weight on the diffusion of contrast media into cartilage

STUDY DESIGN: A comparison of contrast enhancement in the intervertebral disc from two magnetic resonance imaging contrast media in experimental animals. OBJECTIVES: To test the effect of molecular weight on the diffusion of ionic contrast media into the intervertebral disc. SUMMARY OF BACKGROUND DATA: Intravenously administered gadopentetate diffuses similarly into the fibrocartilage of intervertebral discs and herniated disc fragments. Differentiation between recurrent disc fragments and scar tissue via magnetic resonance imaging is optimized by using contrast media, which result in different contrast enhancement of these two tissues. Contrast media of higher molecular weight diffuse more slowly into cartilage; hypothetically, therefore, such media will produce better contrast between scar tissue and recurrent disc fragments. METHODS: Gadopentetate (molecular weight 546) or gadolinium-polylysine (molecular weight 40,000) was injected intravenously into rabbits. The signal intensities of intervertebral disc and muscle tissue were recorded by magnetic resonance imaging at baseline and at pre-determined intervals for 2 hours after injection of the contrast medium. Contrast enhancement in these tissues was calculated in each animal for each contrast medium, and differences in enhancement were tested for significance by a growth-curve model. RESULTS: Contrast enhancement in the intervertebral disc was significantly less with gadolinium-polylysine than with gadopentetate. In muscle, no significant difference between the two media was observed. CONCLUSIONS: Molecular weight affects the diffusion of paramagnetic contrast media into the intervertebral disc. Contrast media of a high molecular weight may produce better contrast between recurrent herniated disc fragments and scar tissue than contrast media of lower molecular weight. This possibility should be rested in further studies.     

Must the patient fast before intravascular injection of a non-ionic contrast medium? Results of a controlled study

PURPOSE: Prospective evaluation of food and fluid restriction before the intravascular injection of a non-ionic contrast medium. MATERIAL AND METHODS: 1000 patients (657 men, 343 women; average age 59 +/- 1/4 5 years) undergoing intravascular contrast injections (CT, phlebography, angiography, urography) were randomly allocated to two groups. Group A had no fluid or solids for at least four hours before the injection (499 cases); group B were allowed unlimited food and fluid (501 cases). Both groups were comparable in all other respects and all were given the non-ionic contrast medium iopamidol (300 mg l/ml). RESULTS: The incidence of acute complications was 3.5%. There was, however, no statistically significant difference between the two groups (p = 0.29). Late adverse reactions were seen in 3.9% patients. There was again no difference between the two groups (p = 0.33). No serious or life threatening complications occurred. CONCLUSION: Restriction of food and fluid before intravascular injection of contrast medium does not reduce the number of adverse side effects. For reasons of patient comfort and compliance, and to achieve adequate hydration, the patient should not fast before injection of contrast.     

Is estrogen necessary after hysteroscopic incision of the uterine septum?

STUDY OBJECTIVE: To evaluate the influence of estrogen after hysteroscopic incision of the uterine septum. DESIGN: Prospective, randomized, blinded study. SETTING: A national referral university hospital. PATIENTS: Fifty women in whom hysterosalpingography (HSG) showed a fundal defect and had septate uterus confirmed by laparoscopy. INTERVENTIONS: Preoperative HSG, hysteroscopic incision of the septum, and postoperative HSG. Four patients were omitted from the analysis because the angle of the uterus could not be corrected, as shown by postoperative HSG. Group 1 (23 women) received conjugated estrogen and progesterone postoperatively and group 2 (23 women) received no hormone. MEASUREMENTS AND MAIN RESULTS: The ratios of the length of the septum to the length of the uterus in the HSGs obtained preoperatively (a/b) and postoperatively (a'/b') were calculated and subtracted from each other (a/b - a'/b'). The means of the subtractions in the two groups were compared. The t test was used for statistical comparison. The results showed no statistically significant difference. CONCLUSION: Estrogen has no apparent role after hysteroscopic incision of the septum.     

Simultaneous multilayer arthrotomography of the temporomandibular joint using photostimulable phosphor computed radiography

OBJECTIVE: To compare the image quality of photostimulable phosphor computed radiography (CR) with that of a conventional screen-film system for simultaneous multilayer arthrotomography of the temporomandibular joint (TMJ). METHODS: X-ray attenuation, resolution and granularity was compared. Simultaneous multilayer tomography of TMJ was performed using a skull phantom and diagnostic quality of bone structures estimated. The clinical outcome is demonstrated in two typical cases. RESULTS: X-ray attenuation was larger with CR. Granularity was more prominent in edge-enhanced CR images and was associated with inferior diagnostic quality. However, it was improved by using a higher tube voltage. Clinical CR without edge enhancement showed a similar resolution to the conventional system but this decreased with enhancement. In an enhanced arthrotomogram, the boundary between contrast medium, bone and soft tissue were clearly defined and a fibrous adhesion also easily seen. CONCLUSION: Photostimulable phosphor CR is an acceptable alternative for simultaneous multilayer arthrotomography of the TMJ.     

Multicentre comparative study of the efficacy and safety of azithromycin compared with amoxicillin/clavulanic acid in the treatment of paediatric patients with otitis media

An open multicentre study was conducted in 484 children between the ages of 6 months and 12 years with otitis media to compare the efficacy, the safety and the tolerance of once-daily azithromycin given for three days versus thrice-daily amoxicillin/clavulanic acid (CA) given for ten days. A satisfactory response (cure plus improvement) was noted 10 to 14 days after the start of treatment in 199 of 215 (92.6%) azithromycin-treated children and in 186 of 198 (93.9%) amoxicillin/CA-treated children. The relationship between treatment and clinical response was independent of chronicity of infection and the presence or absence of a perforated eardrum. Improvement in signs and symptoms of otitis media occurred significantly more rapidly in the children treated with azithromycin. Treatment-related or possibly treatment-related adverse events were recorded in 11 of 243 (4.5%) azithromycin-treated patients and in 20 of 240 (8.3%) treated with amoxicillin/CA. No patients in the azithromycin treatment group were withdrawn from treatment, but six amoxicillin/CA patients, including two < 2 years of age, discontinued treatment prematurely because of adverse events; the difference between treatment groups was statistically significant (p = 0.0146). It is concluded that azithromycin given as an oral suspension once daily for three days is as safe and effective as amoxicillin/CA given thrice daily for ten days in the treatment of children with otitis media.     

The allergic theory of radiocontrast agent toxicity: demonstration of antibody activity in sera of patients suffering major radiocontrast agent reactions

An allergic, immunologic mechanism for certain adverse reactions to radiocontrast agents has been postulated on the basis of clinical and theoretical considerations. One obstacle to the acceptance of this allergic theory has been the inability to demonstrate significant antibodies with specificity for these agents. In our studies, rabbits were immunized with 4 analogues of radiocontrast agents which induced IgG or IgE antibodies specific for the contrast media analogues. Then, to determine if antibodies to contrast agents were present in man a prospective, one-year surveillance of radiocontrast agent reactions was undertaken. Sera from 27 patients suffering severe reactions and 37 control subjects were analyzed by radioimmunoassay for antibodies reactive with radiocontrast media. Binding of radiolabeled contrast media was significantly elevated (p less than 0.01) by the serum globulin fraction of the patients suffering severe reactions. Demonstration of this antibody activity, although not proof of cause and effect between the presence of antibody activity and clinical symptoms, nonetheless adds support to the hypothesis that some adverse reactions to radiocontrast agents are due to antibodies.