Contrast media leakage to the cerebrospinal fluid after intravenous injection. Comparison of stroke patients and controls.

We have tested a method to evaluate leakage of i.v. injected contrast media (CM) through the 3 partitions between blood and cerebrospinal fluid (CSF) in controls and in patients with acute cerebrovascular disease (ACBVD) to detect differences between normal brains and brains with ischemic lesions. High-osmolar (HOCM) and low-osmolar (LOCM) CM were used. In 55 patients and in 41 controls who underwent CT after i.v. contrast administration, lumbar CSF was collected 1 hour after injection and the iodine content in the CSF was measured. The concentration of iodine in CSF was very low, between 0.57 and 11.20 ng/l, and no significant difference could be found between patients and controls or between HOCM and LOCM. We conclude that under the conditions mentioned above, iodine detected in the human lumbar CSF does not reflect the true leakage of contrast agent through the blood-brain barrier.

Coronary angioplasty using a low osmolar nonionic contrast medium. A retrospective angiographic and clinical evaluation.

This study was performed to investigate the occurrence of acute angiographic and clinical complications following PTCA using a low osmolar nonionic contrast medium. Five hundred consecutive PTCA procedures were analyzed retrospectively. The incidence of acute in laboratory complications during PTCA as well as complications occurring during the hospital stay 24 to 48 hours after the procedure were recorded. Occlusion of the dilated artery or a side branch was observed in 19 (3.8%) of the procedures, major dissection in 34 (6.8%), and thrombus in 14 (2.8%). One patient died, 6 (1.2%) required emergency coronary artery bypass grafting (CABG), 4 (0.8%) required an emergency PTCA, and 7 (1.4%) suffered myocardial infarction (MI). Our results show that angiographic findings of thrombus, major dissection and occlusion were serious conditions that related to the clinical complications MI, emergency CABG and re-PTCA. Patients with unstable angina were risk patients for both angiographic and clinical complications. Low rates of intraarterial thrombus formation and coronary artery occlusion indicate good angiographic technique and anticoagulant and antiplatelet medication.

Cerebral thromboembolic complications associated with the use of a nonionic contrast medium in coronary angiography.

Cerebrovascular complications were registered in 11 patients (0.21%) of 5,339, consecutively submitted to coronary angiography with the nonionic contrast medium iohexol (Omnipaque). Six of the patients had diseases predisposing them to thromboembolic complications, 3 of whom earlier had symptoms of cerebral stroke. Excluding these 6, the incidence of cerebral thromboembolic events was 0.10% in patients with no predisposing diseases. Precise catheterization technique and some anticoagulation and antiplatelet activity therapy are definite precautions against these complications, while the role of the contrast medium is still debated.

Biochemical and morphological effects of contrast media on the kidney.

The intravenous use of roentgen contrast media (CM) is associated with a low incidence of renal impairment. This paper considers the intravascular handling and retention of CM in relation to effects on renal function - specifically the ability of the kidney to reabsorb and catabolise low molecular weight proteins. Renal morphology following experimental administration of a high dose of an isotonic dimeric CM (iodixanol at 3 g I/kg) in rats showed numerous, large, protein-containing vacuoles or droplets in the cells of the proximal convoluted tubule. These were fully formed within 3.5 hours. The process of vacuole-formation involving the uptake of CM appears to be analogous to dextran uptake that occurs via fluid phase endocytosis. These vacuoles or CM droplets are abundant for 7 days but then slowly decline over several weeks. The quantitative recovery of (14)C iodixanol (3g I/kg) from the kidneys between 3.5 hours to 7 days after administration was about 1% of the dose, with some 0.2% of the original dose still present at 28 days. Subcellular analysis to determine the site of the radiolabel showed that the (14)C was associated with lysosomal marker enzymes. The CM-induced vacuoles/droplets are most probably giant lysosomes, which contain the intracellularly retained CM. Co-administration of tracer doses of (125)I-labelled cytochrome C with iodixanol showed some impairment of low molecular weight protein reabsorption, but remarkably this process was not effected when the vacuoles were fully formed. The conspicuous morphology of the vacuoles, the CM retention and the transient proteinuria and enzymuria cannot presently be associated with any functionally significant impairment of tubular or cellular processes.

Effects of contrast media on renal epithelial cells in culture.

Proximal and distal tubular cells in culture have been exposed to various roentgen contrast media (CM) at concentrations of 0 to 100 mg I/ml for 22 hours to study cellular mechanisms that may be involved in CM-induced nephropathy. The effects on cell morphology were assessed by electron microscopy and cell viability was evaluated. Levels of brush border and lysosomal marker enzymes in the culture medium were assayed biochemically. Morphological examination showed that CM induced a concentration-dependent formation of large cytoplasmic vacuoles in both cell lines. Cellular damage was observed more frequently after exposure to low-osmolal rather than the iso-osmolal CM iodixanol; the low-osmolal CM causing more cell death and inhibiting cellular growth to a greater degree than did iodixanol. In cultures of both cell lines the CM produced a concentration-dependent increase in brush border marker enzyme activity. While an increase in lysosomal enzyme activity was seen at low concentrations, a decrease in activity occurred at high concentrations. Earlier investigations have demonstrated that the nonionic CM have less pronounced effects on the cell lines studied than ionic CM. The results presented here indicate that the effects of the iso-osmolal nonionic CM (iodixanol) on both the investigated cell lines are less marked than those of the low-osmolal nonionic CM investigated.

Complement activation and histamine release following administration of roentgen contrast media.

Anaphylactoid reactions following administration of reontgen contrast media (CM) have occasionally been described. In this investigation, blood samples for nonallergic human volunteers were exposed to the CM iodixanol (Visipaque), iohexol (Omnipaque), ioxaglate (Hexabrix) and metrizoate (Isopaque 350). The degree of activation of the complement cascade and the amount of free histamine in the samples were estimated. By using a hemolytic assay, a dose-independent complement consumption was detected when salt-free dilutions of the CM were added to human serum. Very little complement consumption was detectable when the concentrations, indicating that in the CM solutions were adjusted toward normal plasma concentrations, indicating that the lack of salts in the CM formulations was responsible for causing the consumption of complement rather than the CM molecules themselves. By using ELISA assay for determination of the terminal complement complex (TCC), no increase in TCC level was detected following the addition of iodixanol to human serum. The results indicate that iodixanol does not activate the complement cascade when added to human serum, and that it is unlikely that anaphylactoid reactions observed in man after CM administration are caused by CM-induced anaphylatoxins. No histamine release was observed following the addition of ioxaglate, metrizoate, iohexol or iodixanol to blood from nonallergic individuals.

Doxorubicin treatment of rabbit renal VX-2 carcinoma: nephrotoxicity, serum parameters and weight.

Serum electrolytes, creatinine, urea, protein, albumin, bilirubin and glucose were examined every 4 days until time of death in rabbits with VX-2 carcinoma implanted in one kidney. The rabbits were treated with doxorubicin, nephrectomy or combinations thereof and observed for up to 1 year. Rabbits treated with doxorubicin only showed a slight creatinine rise initially, but over time creatinine reached almost the same concentration as that in nephrectomized rabbits receiving equivalent doses of doxorubicin. Creatinine concentrations increased significantly above the normal range following nephrectomy combined with doxorubicin. Doxorubicin nephrotoxicity in rabbits occurs at lower doses than previously reported. In all rabbits the parameters except creatinine remained stable within the established normal ranges, except for the last 4 days before time of death in the animals with metastatic disease. Weight loss was the best parameter for making a prognosis for an individual rabbit, since peak weight was noted 16-20 days before death. In experimental work with VX-2 carcinoma, weight is thus the most important indicator of the time at which rabbits not responding to treatment can be put to death to avoid unnecessary suffering before the end of the experiment.

Effects of iodinated x-ray contrast media on renal epithelial cells in culture.

RATIONALE AND OBJECTIVES: To study cellular mechanisms that cause contrast media nephropathy, an in vitro system for proximal and distal tubular cells has been established to evaluate the influence of x-ray contrast media on tubular function. METHODS: Confluent cell cultures of the two renal cell lines, proximal tubule (LLC-PK1) and distal tubule (MDCK), were exposed for 20 hours to 0 to 100 mg iodine/mL of the ionic monomer metrizoate, the ionic dimer ioxaglate, and the non-ionic monomer iohexol. Toxicity was assessed by electron microscopy, cell viability, and biochemical assays of brush-border and lysosomal marker enzymes. RESULTS: The results demonstrated a concentration-dependent toxic effect from the contrast media on cellular appearance consisting of an increased vacuolization and on the activity of brush-border and lysosomal marker enzymes in cells and in culture media. CONCLUSION: The results, in which the nonionic x-ray contrast media iohexol appeared to be less toxic than the ionic x-ray contrast media investigated, demonstrated that defined renal cells in culture are valuable tools in studies regarding renal toxicity of x-ray contrast media.

Lack of an immune response to Albunex, a new ultrasound contrast agent based on air-filled albumin microspheres.

Albunex is a new ultrasound contrast agent consisting of air-filled microspheres of heat-aggregated human albumin suspended in a 5% (w/v) solution of human albumin for infusion. The structural alterations induced in the albumin molecules during heat aggregation may cause the formation of new epitopes that may provoke an immunological response in recipients. To assess the possible immunogenicity of the contrast agent, 34 healthy volunteers were randomized to receive four injections of either Albunex or 5% human serum albumin (0.01 ml/kg) at 4-week intervals. Analysis of blood samples taken 3 weeks after each injection did not reveal any formation of IgE or IgG antibodies directed against the Albunex microsphere protein or albumin in any of the recipients. The evaluation of novel enzyme immunosorbent assays developed to detect the presence of these specific IgE and IgG antibodies is described. It was also investigated whether the heat-aggregated microsphere albumin was structurally altered in such a way that it could be recognized by cat albumin specific IgE, present in the sera of individuals allergic to cat albumin. 187 serum samples shown to contain elevated levels of cat albumin specific IgE were used in the study. No cross-reactive binding of the heat-aggregated human albumin to anticat albumin IgE could be detected. There is no evidence from the present studies that the heat-aggregated albumin of the Albunex microspheres will provoke an immunological reaction upon repeated injections or cause an adverse reaction when administered to allergic individuals having cat albumin as one of their allergens.

Intravascular contrast media and thrombin generation.

This study focuses on the effect of contrast media (CM) on thrombin generation. In vitro studies consisted of incubating nonanticoagulated whole blood with ionic CM (sodium meglumine diatrizoate, ioxaglate), nonionic CM (iohexol, iopamidol) or glucose in plastic tubes. Thrombin generation was assessed by measuring F1 + 2, ATM and FpA levels in plasma using ELISA assay kits. In a separate protocol, the procoagulant activity of 3 nonionic CM (iohexol, iopamidol, and iopromide) was investigated by one-stage plasma recalcification time method. Rabbit brain tissue thromboplastin and physiologic saline were used as standard and experimental controls. Incubation of ionic and nonionic CM with whole blood did not enhance thrombin generation compared to glucose control. Similarly, the plasma recalcification times were not significantly shortened by either of the 3 nonionic CM tested. These studies suggest that ionic and nonionic CM exhibit different levels of anticoagulant properties in vitro and the latter are not procoagulant materials.

Systemic and local silver accumulation after total hip replacement using silver-impregnated bone cement.

In a patient, at revisional Christiansen total hip arthroplasty, silver-impregnated bone cement was used as prophylaxis against deep infection. Five years later the patient developed serious neurological deficits, and the prosthesis was loose. The loose Christiansen prosthesis and the silver-impregnated bone cement were removed and a Charnley prosthesis inserted. Intra-operatively the concentration of silver in fluid drawn from the hip joint was assessed to be about 1000 times the normal serum reference value, and tissue samples from the acetabulum were densely impregnated with silver. During the following 2 years the serum concentration of silver decreased from more than 60 times to 20 times the normal; simultaneously the patient partially recovered from her grave muscle paralysis.

[Diaper dermatitis. Classification, occurrence, causes, prevention and treatment]. / Bleiedermatitt. Klassifikasjon, forekomst, årsaker, forebygging og behandling.

Diaper dermatitis is a multifactorial dermatological disorder characterized by inflammation in the diaper area. About half of all babies and old people in need of care experience light dermatitis, while 20% have moderate and 5% severe dermatitis. Friction from the diaper, occlusion, irritation from faeces, ammonia, detergents, candida albicans, proteolytic and lipolytic enzymes and moisture deposited on the epidermis cause damage at the stratum corneum layer of the epidermis. Diaper dermatitis is caused by a combination of mostly irritant effects. Compounds that infiltrate the skin can aggravate the reaction to the damaged epidermis. The barrier function of epidermis must be restored in order to prevent and treat diaper dermatitis.

Studies on the allergenicity of the amino-terminal epitope (Bet v I 23-38) from birch pollen allergen.

An N-terminal peptide of the major allergen of birch (Bet v I 23-38) was selected for studying the activity of this segment on the basis of optimal hydrophilicity as it was tentatively suggested to be a surface exposed epitope. In addition two control peptides in the region 1-38 were similarly used for comparative assignment of the allergenicity. Peptide analogues from the amino acid terminal region, amino acid residues No. 23-38 of Bet v I, were synthesized by semiautomatic solid-phase peptide synthesis. In vitro and in vivo biological activity studies were performed on these analogous peptides. The IgE-binding capacity of the synthetic peptide 23-38 was examined using the following tests: specific IgE inhibition, skin prick test, nasal provocation and Prausnitz-Küstner inhibition. The results of these investigations suggested that the region 23-38 from the birch and hazel major allergen encompassed a single haptenic epitope.

Atrial natriuretic factor in cats subjected to acute myocardial ischaemia.

Eighteen anaesthetized open chest cats were subjected to 10, 30, or 50 min occlusion of the left anterior descending coronary artery (LAD). Heart rate, left ventricular end-diastolic (LVEDP) and systolic pressure (LVSP), and dp/dt were continuously recorded during the experiments. Prior to LAD-occlusion, and just before termination of the experiments, blood samples were collected from the left femoral artery for measurements of atrial natriuretic factor (ANF), catecholamines, electrolytes, urea, and creatinine. Simultaneously, biopsies were collected from the right auricular wall. The tissue was embedded in Lowicryl K4M, and ultrathin sections were incubated with anti-ANF antibodies and secondary antibodies conjugated to gold particles. The density of ANF-containing atrial-specific granules labelled with gold particles was morphometrically calculated. LVEDP increased significantly in all three time groups, and when pooling the pre- and postocclusion values, there was an increase from 5.1 +/- 0.4 to 10.3 +/- 1.2 mmHg (p < 0.05). The noradrenaline level increased from 0.93 +/- 0.18 to 2.34 +/- 0.75 nmol l-1 (p < 0.05) after LAD-occlusion. Similarly, the mean plasma level of ANF in the 18 cats increased from 57.6 +/- 11.9 to 98.9 +/- 22.6 pmol l-1 (p < 0.05). Atrial granular density appeared to decline after 10 min of occlusion (from 0.141 +/- 0.017 to 0.127 +/- 0.022 granules-1 microns 2 sarcoplasm), and after 30 min there was a significant decrease (0.080 +/- 0.012 granules/microns 2, p < 0.05). However, after 50 min occlusion the granular density was almost restored (0.133 +/- 0.017 granules/microns 2). Plasma ANF showed a positive linear correlation to LVEDP and to the noradrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS)

Immune-mediated hemolysis associated with the administration of a radiographic contrast medium.

A female patient developed serious hemolysis in association with the injection of a radiographic contrast medium (RCM). Serologic investigation of her serum suggested complement-mediated hemolysis, induced by an RCM-dependent IgM antibody in her serum. The antibody was of high titer and low avidity. The antibody showed cross-reactions with related radiographic contrast media and reacted only with group I adult RBCs.

The structural requirements of epitopes with IgE binding capacity demonstrated by three major allergens from fish, egg and tree pollen.

Three major allergens from cod fish, egg white and tree pollen, were characterized by studies on their allergenic and antigenic structures. The major allergen of cod fish, Allergen M "parvalbumins pI 4.75", is composed of 113 amino acid residues with a molecular weight of 12,328 daltons. It comprised three domains, AB, CD and EF, consisting of 3 helices interspaced by one loop. Each of the loops of the CD and EF domains each coordinates one Ca2+. The antigenicity and allergenicity of Allergen M was deduced from studying the modified protein and some particular synthetic peptides. Three sites were encompassing IgE binding epitopes namely peptides 33-44, 65-74 and 88-96. A novel peptide (49-64), of the CD-domain, was demonstrated to be allergenically/antigenically active and cross reactive with birch pollen allergen, which incidentally was used as a negative control. This site encompassed two repetitive sequences (D-E-D-K) and (D-E-L-K), suggested to be mutually critical for the specificity of antibody binding. This hypothesis was reconfirmed by SPPS of several analogous peptides of region 39-64. Furthermore, peptide 88-103 of the EF-domain was similarly synthesized; it functioned as a monovalent hapten, blocking and not eliciting allergic reaction. Moreover, peptide 13-32 of domain AB, the non-calcium binding domain, was thoroughly tested. The results of PK inhibition showed clear activity and the peptide was found to function at the level of a divalent determinant. Ovalbumin (OA) is the most dominant of five major allergens of egg white and universally used as model protein. OA allergenic epitopes were shown to be mainly determined by the primary structure and depend on certain peptide chain length. The N-terminal decapeptide (OA 1-10) was shown to react with reaginic IgE. Direct skin test on egg allergic patients, showed no activity and the site was therefore concluded to encompasses one single Ig binding haptenic epitope. Peptide OA 323-339, was demonstrated to be valuable in studies of T-cell recognition of protein antigens. Three analogous peptides of this region were prepared and clearly shown to be immunogenic in rabbits and to bind specific IgE from patients allergic to egg. OA 323-339 was concluded to encompass an allergenic and antigenic epitope which was recognized by human and rabbit B-lymphocytes. Eight peptides in the region 11-122 were similarly synthesized. A test battery was performed to study this region using rabbit polyclonal antibodies and human specific IgE. Some of these sites were involved in binding of particular Ig paratopes. Five immunogenic peptides from the major allergens of tree pollen extracts (segment 23-38), were synthesized. The selection of those peptides was setteled using two algorithms for providing the optimal hydrophobicity.(ABSTRACT TRUNCATED AT 400 WORDS)