Routine chest X-ray is not required after a low-risk central venous cannulation.

BACKGROUND: Knowledge of the radiographic catheter tip position after central venous cannulation is normally not required for short-term catheter use. Detection of a possible iatrogenic pneumothorax may nevertheless justify routine post-procedure chest X-ray. Our aim was to design a clinical decision rule to select patients for radiographic evaluation after central venous cannulation. METHODS: A total of 2230 catheterizations performed using external jugular, internal jugular or subclavian venous approaches during a 4-year period were included consecutively. Information on patient data and corresponding procedures was recorded prospectively. A post-procedure chest X-ray was obtained after each cannulation. RESULTS: Thirteen cases (0.58%) of cannulation-associated pneumothorax were identified. The risk of pneumothorax after a technically difficult (1.8%) or subclavian (1.6%) cannulation was significantly higher than after cannulation not considered as difficult (0.37%) or performed using other routes (0.33%). Clinical signs of pneumothorax within 8 h of cannulation were found in all seven patients with pneumothorax requiring specific treatment. A new clinical decision rule for radiographic evaluation after central venous cannulation based on the results of the present study shows that 48% of the post-procedure chest X-rays performed in our patients were clinically redundant. CONCLUSION: Clinical symptoms were reported in all patients with pneumothorax requiring specific treatment. Approximately half of the post-procedure chest X-ray controls could be avoided using the proposed clinical decision rule to select patients for radiographic evaluation after central venous cannulation. A large prospective multi-centre study should be carried out to further evaluate this decision rule.

Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk.

The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.

The incidence and risk of central venous catheter malpositioning: a prospective cohort study in 1619 patients.

Central venous catheters are used in various hospital wards. An anterior-posterior chest X-ray is usually obtained soon after cannulation to assess the location of the catheter tip. This prospective clinical study was designed to determine the radiographic catheter tip position after central venous cannulation by various routes, to identify clinical problems possibly associated with the use of malpositioned catheters and to make a cost-benefit analysis of routine chest X-ray with respect to catheter malposition. A total 1619 central venous cannulations were recorded during a three-year period with respect to patient data, information about the cannulation procedures, the radiographic catheter positions and complications during clinical use. The total incidence of radiographic catheter tip malposition, defined as extrathoracic or ventricular positioning, was 3.3% (confidence interval 25 to 4.3%). Cannulation by the right subclavian vein was associated with the highest risk of malposition, 9.1%, compared with 1.4% by the right internal jugular vein. Six of the 53 malpositioned catheters were removed or adjusted. No case of malposition was associated with vascular perforation, local venous thrombosis or cerebral symptoms. We conclude that the radiographic incidence of central venous catheter malpositioning is low and that clinical use of malpositioned catheters is associated with few complications. However, determination of the catheter position by chest X-ray should be considered when mechanical complications cannot be excluded, aspiration of venous blood is not possible, or the catheter is intended for central venous pressure monitoring, high flow use or infusion of local irritant drugs.

IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5.

In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.

SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients.

SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.

European quadricentric evaluation of a breast MR biopsy and localization device: technical improvements based on phase-I evaluation.

Our purpose was to report about technical success, problems and solutions, as experienced in a first multicentre study on MR-guided localisation or vacuum biopsy of breast lesions. The study was carried out at four European sites using a dedicated prototype breast biopsy device. Experiences with 49 scheduled localisation procedures and 188 vacuum biopsies are reported. Apart from 35 dropped indications, one localisation procedure and 9 vacuum biopsies were not possible (3 times space problems due to obesity, 2 times too strong compression, 3 times impaired access from medially, 2 times impaired access due to a metal bar). Problems due to too strong compression were recognised by repeat MR without compression. During the procedure problems leading to an uncertain result occurred in eight vacuum biopsies, two related to the procedure: one limited access, and one strong post-biopsy enhancement. Improvements after phase-I study concerned removal of the metal bar, development of an improved medial access, of a profile imitating the biopsy gun, optimisation of compression plates and improved software support. The partners agreed that the improvements answered all important technical problems.

Multicenter study for the evaluation of a dedicated biopsy device for MR-guided vacuum biopsy of the breast.

The purpose of this multicenter study was to determine the accuracy and clinical value of a dedicated breast biopsy system which allows for MR-guided vacuum biopsy (VB) of contrast-enhancing lesions. In five European centers, MR-guided 11-gauge VB was performed on 341 lesions. In 7 cases VB was unsuccessful. This was immediately realized on postinterventional images or direct follow-up combined with histopathology-imaging correlation; thus, a false-negative diagnosis was avoided. Histology of 334 successful biopsies yielded 84 (25%) malignancies, 17 (5%) atypical ductal hyperplasias, and 233 (70%) benign entities. Verification of malignant or borderline lesions included reexcision of the biopsy cavity. Benign histologic biopsy results were verified by retrospective correlation with the pre- and postinterventional MRI and by subsequent follow-up. Our results indicate that MR-guided VB, in combination with the dedicated biopsy coil, offers the possibility to accurately diagnose even very small lesions that can only be visualized or localized by MRI.

Image quality and safety after iodixanol in intravenous urography; a comparison with iohexol.

A double-blind, randomized phase III study compared intravenous urography in 100 adult patients receiving iodixanol 320 mgI ml-1 (Visipaque) with 99 patients receiving iohexol 350 mgI ml-1 (Omnipaque). The aim of the study was to investigate differences in image quality between a non-ionic dimeric contrast medium (CM) and a non-ionic monomer at 40 ml per patient and 60-100 ml per patient volume levels. There were no statistically significant differences between iodixanol and iohexol with respect to overall diagnostic information, which was found to be optimal in 86% and 79%, respectively. Immediately after the injection, the renal border was better delineated with iohexol than with iodixanol (p = 0.0001). Marked papillary blush occurred more often in the iodixanol group (16%) than in the iohexol group (0%), as did visualization of the collecting ducts (24% vs 5%) (p = 0.001). The incidence of adverse events was similar and low for both contrast media. In patients who received the higher doses of CM (60-100 ml), the frequency of discomfort was significantly lower after iodixanol than after iohexol (p = 0.006). We conclude that, in intravenous urography, iodixanol provides at least as good image quality as does iohexol. Iodixanol may cause less discomfort than iohexol, in particular when larger volumes of CM are injected.

Neural tolerance of the non-ionic dimers iodixanol and iotrolan and the non-ionic monomer iopamidol during myelography in non-anaesthetised rabbits.

PURPOSE: The neural tolerance of the recently introduced dimer iodixanol (320 g I/l) was compared with that of the dimer iotrolan (300 g I/l) and of the monomer iopamidol (300 g I/l), both used in clinical myelography. MATERIAL AND METHODS: Non-anaesthetised rabbits were injected into the cisterna magna with Ringer's solution (control) or contrast media (CM) at doses of 1.0 or 0.5 ml/kg b.w. The behaviour of the animals (10 in each of 7 groups) was evaluated for signs of excitation and depression during the first 3 hours after injection. RESULTS: At the dose level of 1.0 ml/kg b.w., iodixanol produced no seizures but did cause focal twitching in 4/10 rabbits. Iopamidol produced grand mal seizures in 2/10 and hyperexcitability in 4/10 rabbits. Iotrolan produced generalised grand mal seizures in 8/10 rabbits, an incidence of excitation significantly greater than that of iodixanol (p < 0.01) and iopamidol (p < 0.05). The excitative effects of iodixanol were not significantly different from those of iopamidol and Ringer's solution. All 3 CM produced similar depressive effects on rabbit behaviour. Ringer's solution caused no depressive effects (p < 0.01). A clear dose response was produced with all 3 CM after treatment with a lower dose of 0.5 ml/kg b.w. CONCLUSION: The results indicate that the neural tolerance in the rabbit of iodixanol is higher than that of iotrolan, and is at least equal to that of iopamidol.

CNS-effects from subarachnoid injections of iohexol and the non-ionic dimers iodixanol and iotrolan in the rabbit.

The neural tolerance of the new non-ionic dimer iodixanol was compared with that of the clinically used monomer iohexol and the dimer iotrolan. Behaviour of non-anaesthetised rabbits was monitored for 3 hours after intracisternal injection, at a dose-volume of 1 ml/kg of iodixanol 150 mg I/ml, iodixanol 320 mg I/ml, iohexol 350 mg I/ml, or iotrolan 300 mg I/ml (10 rabbits in each group). Iotrolan induced generalized seizures in 5 rabbits, iodixanol 320 mg I/ml in 2 rabbits, and iodixanol 150 mg I/ml in one rabbit. No excitative changes were observed in rabbits, iodixanol 320 mg I/ml in 2 rabbits, and iodixanol 150 mg I/ml in one rabbit. No excitative changes were observed in rabbits injected with iohexol, but compared with the dimeric contrast media the difference was not significant. Iohexol produced significantly more severe depressive changes than iodixanol 150 mg I/ml (p < 0.01), iodixanol 320 mg I/ml (p < 0.05), and iotrolan 300 mg I/ml (p < 0.05). The results indicate that the excitative neurotoxic potential of the dimer iodixanol is likely to be lower than that of the clinically used dimer iotrolan, but slightly higher than that of iohexol. It may be expected that both dimers will produce a lower frequency of minor neurological adverse reactions than iohexol.

Vasoconstriction of isolated arteries induced by angiographic contrast media. A comparison of ionic and non-ionic contrast media iso-osmolar with plasma.

Angiographic contrast media (CM) may cause both vasodilatation and vasoconstriction, effects that can only be partly be explained by the media's hyperosmolality. The present study describes a CM-induced vasoconstriction of isolated rabbit coronary arteries that depends on chemotoxicity and ion content of the CM. Rings of arteries were mounted in tissue baths and the constrictions induced by different CM were measured. Iotrolan and iodixanol (non-ionic dimers) caused the most powerful constrictions followed by iohexol (non-ionic monomer) and mannitol. Ioxaglate (ionic dimer) and diatrizoate (ionic monomer) caused no or weak constrictions. By comparing these findings with previous studies, it is concluded that non-ionic media cause vasoconstriction due to depolarization of the smooth muscle cells, an effect that for iohexol can be counteracted by addition of 30 mM NaCl. The ionic media seem to cause hyperpolarization of the cells. This difference between non-ionic and ionic CM might be one of the reasons for the lower tendency of non-ionic CM to cause vasodilatation clinically.

Contrast medium-induced vasoconstrictions. An investigation of the vasoconstrictive action of iohexol in isolated rabbit coronary arteries.

Angiographic contrast media (CM) may cause both vasodilatation and vasoconstriction. This study evaluates a contrast medium-induced vasoconstriction that occurs when isolated arteries are exposed directly to a CM. Segments of rabbit coronary arteries were mounted in tissue baths containing buffer solution. During the experiments the buffer solution was exchanged with iohexol iso-osmolar with plasma, which caused a temporary vasoconstriction of the vessel segments. The constriction did not depend on the degree of oxygenation of iohexol. The endothelium was not involved in the vasoconstriction. Prazosin slightly decreased the vasoconstriction and a small part of the constriction might thus depend on liberation of norepinephrine by iohexol. The constriction was totally inhibited by the calcium antagonist nifedipine, while it was augmented by addition of low concentrations of KCl to ihoexol. It is concluded that the otherwise safe CM iohexol causes vasoconstriction in vitro by depolarizing the smooth muscle cells and the nerve terminals in the vessel wall.

Effects on erythrocyte aggregation and blood coagulation from iohexol solutions with and without sodium chloride. An in vitro study on the role of ion concentration and osmolality.

Solutions of the nonionic monomeric contrast medium iohexol (300 mg I/ml) with and without added NaCl were investigated for effects on red blood cell aggregation and blood coagulation. Three volumes of a test solution were mixed in test tubes with one volume of human blood. During 30 min samples of the mixture were taken for investigation. Six test solutions were used: 1) iohexol, 2) iohexol+glucose 280 mM, 3) iohexol+NaCl 150 mM, 4) glucose 280 mM, 5) glucose 140 mM+NaCl 75 mM, 6) NaCl 150 mM. Test solutions with NaCl caused no aggregation. Test solutions without NaCl always caused macroscopic red cell aggregates. These aggregates always disappeared when saline was added to the sample. The macroscopic red cell aggregates could be dispersed to microscopic aggregates by shaking the test tubes. During the next 30 min macroscopic aggregates returned in the glucose solution but not in the iohexol solutions. In 30 min, blood mixed with iohexol solutions never coagulated while blood layered on top of the same iohexol solutions always coagulated. Blood mixed with solutions 5 and 6, both without iohexol, always coagulated. It is concluded that adding 150 mM NaCl to iohexol did not eliminate its ability to anticoagulate whole blood, but inhibited its ability to aggregate red cells. This inhibition was not caused by the osmotic effects of the added NaCl.

Reducing arrhythmogenic effects in the isolated heart enriching roentgen contrast media with electrolytes. Survey and present state.

A review of the literature on the effects of adding electrolytes to ionic as well as nonionic contrast media (CM) in the isolated heart model reveals that both ionic and nonionic CM favor from such addtion, if the added electrolytes are balanced with respect to each other. By enriching nonionic monomeric as well as dimeric CM with such a balanced electrolyte solution, the risk of ventricular fibrillation is reduced and myocardial contractibility is improved compared to nonionic CM without such enrichment. The new nonionic dimer iodixanol is slightly hypotonic to plasma in concentrations suitable for coronary arteriography. The water solution of iodixanol therefore contains an osmotic space in which electrolytes can be added, therby making it isotonic with plasma.

Vasodilatative and vasoconstrictive effects of angiography contrast media.

During angiography contrast media (CM) induces changes in vessel tone. The pathophysiological reasons for this are poorly understood. In this short review the anatomical structures and physiological factors involved in vessel tone are described, and previous and recent findings in vitro and in vivo concerning the effect of CM on vessel tone are discussed. Although multifactorial, the main effect seems to result from a direct action of the CM on the vessel wall. For a particular CM formulation, the effect is due to a combination of its osmolality, molecular properties as well as electrolyte content. In vitro experiments performed in iso-osmolar solutions of pure CM suggest the CM interfere with the cellular mechanisms controlling intracellular calcium. When injected intravascularly, CM may cause either vasodilatation and vasoconstriction. Vasodilatation is the most frequent effect when CM is injected into a vessel while vasoconstriction is relatively uncommon. Both vasodilatation and vasoconstriction can be caused by all types of CM.

Adverse reactions in myelography.

An attempt was made to assess the usefulness of using animal models to predict the neural tolerability in man of iodinated contrast media (CM) in general, and of the new nonionic dimer iodixanol in particular. For this purpose, the results from 6 animal experiments evaluating excitative and depressive effects of subarachnoidally injected CM in nonanesthetized rabbits were compared with the results from 22 randomized double-blind clinical trials dealing with post-myelographic adverse reactions. Comparisons were made as regards the nonionic monomers metrizamide, iohexol, and iopamidol, and the dimer iotrolan. The results seem to justify the conclusion that the convulsive effects of CM can be reliably predicted from animal experiments. The animal model cannot be used to predict specific types of nonconclusive adverse reactions in man, but reflects well the differences in frequencies of minor reactions following clinical myelography with different nonionic CM. In general, the neural tolerability of iodixanol may be expected to be better than that of the nonionic monomers and approximately equal to that of iotrolan.

Calcium antagonistic effects of an angiographic contrast medium in vitro. A comparison of the effects of iohexol with the effects of nifedipine in isolated arteries.

RATIONALE AND OBJECTIVES: Vasodilatation is a well-known side effect of contrast media. Contrast media inhibit the action of vasoconstrictors. The nonionic contrast medium, iohexol, inhibits vasoactive substances to a lesser extent than ionic contrast media. Iohexol inhibited the action of vasoconstrictors in a way that raised suspicion of a calcium antagonistic effect of the medium. The authors test this hypothesis by comparing the inhibitory effect of iohexol with the inhibitory effect of a calcium antagonist (nifedipine). The vasoconstrictors were KCl, which depends on potential-operated calcium channels, and histamine, endothelin-1, and prostaglandin F2 alpha (PGF2 alpha), which depend on receptor-operated calcium channels. METHODS: Segments of rabbit coronary arteries were mounted between two L-shaped prongs in tissue baths containing calcium-free buffer, calcium-free buffer with 10(-8) M nifedipine, or iohexol. One of the vasoconstrictors, KCl, histamine, endothelin-1, or PGF2 alpha, was added to induce a level of activation. Thereafter, increasing concentrations of CaCl2 were added in a stepwise manner, and the contractile responses of the vessel segments were recorded. RESULTS: Addition of CaCl2 caused concentration-dependent vasoconstrictions in the buffer. The effect of adding CaCl2 was inhibited in the buffer with nifedipine and in iohexol when the vessels were activated with histamine, endothelin-1, or PGF2 alpha. When the vessels were activated with the potential-operated calcium channel-dependent vasoconstrictor, KCl, the effect of adding CaCl2 was inhibited in the buffer with nifedipine but not in iohexol. CONCLUSIONS: In vitro, iohexol had the same effect as the calcium antagonist nifedipine on the action of receptor-operated calcium channel-dependent vasoconstrictors. This suggests a calcium antagonistic effect of iohexol on the action of the ROC.

Effects of vasoconstrictors on rabbit coronary arteries exposed to iohexol with addition of electrolytes (sodium and calcium).

RATIONAL AND OBJECTIVES: A well-known side effect of contrast media (CM) is vasodilation. Different types of CM in vitro inhibit the action of vasoconstrictors to various degrees. The nonionic CM iohexol inhibits the action less than ionic CM. In this study, the authors investigate whether the addition of electrolytes to iohexol causes less inhibition of the vasoconstrictors. Vasoconstriction dependent on potential-operated calcium channels (POCs) (potassium chloride), or receptor-operated calcium channels (ROCs) (histamine, endothelin-1, and prostaglandin F2 [PGF2 alpha]) was specifically studied. METHODS: Segments of rabbit coronary arteries were mounted between two L-shaped prongs in tissue baths with buffer solution or solutions of iohexol (140 mg I/mL) with addition of different concentrations of NaCl and CaCl2. The responses of the vessels to increasing concentrations of a vasoconstrictor were examined. Concentration of vasoconstrictor versus contractile response curves were plotted, and the maximal contraction of the vasoconstrictor (Emax) and half maximal constriction were calculated. RESULTS: Addition of 30 mM NaCl and 1.5 mM CaCl2 caused a vasoconstriction to KCl in iohexol almost identical to its vasoconstriction in buffer. Higher concentrations of NaCl caused decreasing Emax of all vasoconstrictors. The inhibition of the ROC-dependent vasoconstrictors could not be normalized by the addition of electrolytes. CONCLUSIONS: The inhibition of the POC-dependent vasoconstrictor was caused by "ion toxicity" of iohexol. The inhibition of the ROC-dependent vasoconstrictors was caused by other mechanisms, in a manner compatible with a blocking effect on ROCs.

Effects of nonionic monomeric and dimeric contrast media on the twitching reaction of the rat. Importance of osmolality and electrolyte content.

RATIONALE AND OBJECTIVES: The authors established a rat model of the twitching reaction to contrast media in striated muscle and investigated the influence of nonionic contrast medium on the twitching reaction regarding the nonionic dimer iodixanol compared with the monomer iohexol and the dimer iotrolan. The authors also studied the influences from the electrolyte additions of iodixanol. METHODS: The interval from start of contrast medium injection to start of head movement was compared for iohexol (140 and 350 mg iodine/mL), iodixanol (150 and 320 mg iodine/mL), and iotrolan (300 mg iodine/mL). Comparison was made with mannitol and mannitol containing the same electrolyte concentrations as iodixanol (150 and 320 mg iodine/mL). RESULTS: No differences in latency period were found between iohexol 140 mg iodine/mL (isotonic) and 350 mg iodine/mL (880 mOsm/kg). Iodixanol caused a lesser effect on the twitching reaction than the iohexol solutions and iotrolan. When the electrolytes of iodixanol were added to mannitol (300 mOsm/kg), there was a later onset of the twitching reaction than with electrolyte-free mannitol. CONCLUSIONS: Differences in latency period caused by a change in osmolality were not found. The interval for a twitching reaction was longer with iodixanol than with iohexol, iotrolan, and iso-osmolar mannitol. The weak effect of the iodixanol solution was probably partially caused by the electrolyte content.