Cross-reactivity patterns of T cells specific for iodinated contrast media

BACKGROUND: Approximately 3% of patients exposed to iodinated contrast media develop delayed hypersensitivity reactions. OBJECTIVE: We wanted to better understand the molecular basis of contrast media cross-reactivity. METHODS: Cross-reactivity was assessed by skin testing and measurement of T-cell activation (CD69 upregulation) and proliferation ((3)H-thymidine uptake, 5,6-carboxyfluorescein diacetate succinimidyl ester staining) of PBMCs, T-cell lines, and T-cell clones of 2 patients with delayed hypersensitivity reactions to iohexol and iomeprol, respectively. Thirteen different contrast media and potassium iodide were compared. RESULTS: Skin testing and analyses of PBMCs, T-cell lines, and clones showed broad cross-reactivity in both patients. Broad as well as more restricted cross-reactivity patterns were found in iohexol-specific and iomeprol-specific CD4(+) T-cell clones, whereas 1 iomeprol-specific CD8(+) T-cell clone showed no cross-reactivity at all. The reactivity to equimolar concentrations of iohexol and its dimer iodixanol was very similar, suggesting that the dimer was not more stimulatory than its monomer. Consistently low reactivity to iobitridol was found in both patients, but never to iodide. A frequency analysis of contrast medium-specific peripheral T cells gave values between 0.6 % (iomeprol) and 0.05 % (iobitridol). CONCLUSION: Clinically observed cross-reactivity between different contrast media is a result of the presence of contrast media-specific T cells, some of which show a broad cross-reactivity pattern. Iodide ions, known to be present at low concentration in contrast media solutions, do not seem to be the causative moiety. CLINICAL IMPLICATIONS: Detailed in vitro analysis might help identify noncross-reactive contrast media.     

Genetic and environmental influences on plasma homocysteine: results from a Danish twin study

BACKGROUND: Increased plasma homocysteine has been linked to many clinical conditions including atherosclerosis and ischemic stroke. We assessed the genetic and environmental influences on homocysteine in adult twins and tested the influence of 3 candidate polymorphisms. METHODS: Homocysteine was analyzed in 1206 healthy twins, who were genotyped for 3 polymorphisms: MTHFR 677C>T, MTR 2756A>G, and NNMT (dbSNP: rs694539). To perform quantitative trait linkage analysis of the MTHFR locus, the genotyping was supplemented with 2 genetic markers localized on each site of the MTHFR locus. The twin data were analyzed using biometric structural equation models as well as a combined association and linkage analysis in 2 age cohorts. RESULTS: Age, sex, and MTHFR genotype have a significant impact on homocysteine concentrations, whereas the other genotypes were not associated with homocysteine concentrations. The variance in homocysteine could be solely ascribed to additive genetic and nonshared environmental factors, with an estimated additive genetic proportion of total variation at age 18-39 years of 0.63 (95% CI, 0.53-0.71) and at age 40-65 years of 0.27 (95% CI, 0.10-0.41). The impact of the MTHFR locus is estimated to explain 53% (95% CI, 0.07-0.67) of the total phenotypic variation in persons 18-39 years old and 24% (95% CI, 0.00-0.39) in persons 40-65 years old, i.e., almost all additive genetic variance. CONCLUSIONS: Homocysteine concentrations have a high heritability that decreases with age. The MTHFR gene locus is responsible for almost all the variation attributable to genetic factors, leaving very little influence of other genetic variations.     

Epidemiologie der Hepatitis-B-Virusinfektion in Deutschland*

Zusammenfassung Hintergrund und Ziel:  Zur Epidemiologie der chronischen Hepatitis-B-Virus-(HBV-)Infektion in Deutschland ist wenig bekannt. Die jetzige Studie analysiert demographische, sozio?konomische und virologische Charakteristika einer Kohorte von in Deutschland lebenden HBV-Infizierten. Patienten und Methodik:  Im Rahmen des Hepatitis-Kompetenznetzes wurden in den vergangenen 5 Jahren konsekutiv 250 Patienten erfasst, die wegen einer chronischen HBV-Infektion ambulant vorstellig wurden. Ergebnisse:  Das mittlere Alter betrug 40,5 ± 14,6 Jahre. M?nner überwogen mit 63,2%. Die HBV-DNA war bei 12,8% der Personen negativ, die Glutamat-Pyruvat-Transaminase (GPT) bei 56,3% normal; auch bei DNA-Werten > 1 Mio. Kopien/ml war die GPT in 38% normal („Immuntoleranz“). Je etwa ein Drittel der Patienten stammte aus Deutschland, der Türkei und einer gro?en Zahl anderer L?nder (82 Patienten aus 34 verschiedenen L?ndern). Die Arbeitslosenrate war bei den aus der Türkei und anderen L?ndern stammenden Personen mehr als dreimal so hoch wie bei deutschst?mmigen; diese Unterschiede bestehen aber auch bei nicht HBV-infizierten Personen. In der Gesamtgruppe waren die HBeAg-Negativen gegenüber den HBeAg-Positiven mit 66,4% versus 33,6% deutlich h?ufiger. Etwa 40% der biopsierten Personen hatte eine deutliche Fibrose (F2–4). Multivariat korrelierte das Fibrosestadium nur mit Alter und GPT, nicht aber mit DNA oder anderen Variablen. Eine laufende antivirale Therapie erhielten 38,4%, wobei die Behandlungsrate mit der H?he von DNA und GPT anstieg. Die meisten Behandelten erhielten Lamivudin (58%), Adefovir (31%) oder beide Medikamente (5%). Nur je 3% erhielten Interferon oder andere Substanzen. Schlussfolgerung:  Die jetzige Kohortenstudie zeigt, dass im Ruhrgebiet etwa zwei Drittel aller HBV-Infizierten der Migrantenpopulation entstammen, wobei hier ?konomische Probleme besonders ausgepr?gt sind. Es sollten deshalb spezielle Programme für Migrantenpopulationen entwickelt werden, die die Erkennung der hier so h?ufigen HBV-Infektion und die Aufkl?rung über die damit verbundenen individuellen und infekti?sen Risiken zum Ziel haben. * Diese Arbeit wurde durch das vom Bundesministerium für Bildung und Forschung gef?rderte Kompetenznetz Hepatitis (Hep-Net) unterstützt.     

Evaluation of an end-tidal portable ETCO2 colorimetric breath indicator (COLIBRI)

Evaluation of tube position is important after in-hospital and prehospital emergency intubation. Colorimetric breath indicators are devices for immediate control of tube positioning by showing a color change according to end-tidal CO2 (ETCO2) concentrations. We hypothesized that colorimetric breath indicators can yield reliable results for confirmation of tube position. The aim of this study was to evaluate the effectiveness and safety of a new colorimetric breath indicator (Colibri, ICOR AB, Bromma, Sweden) in 147 patients during general anesthesia, in critically ill patients, during transport to in-hospital interventions, and in a study design after insertion of a second tube into the esophagus in long-term ventilated patients. The Colibri was attached between the respective airway and ventilatory tubing. Seventy-three patients were investigated during general anesthesia, 39 patients were observed during long-term ventilation with an average duration of 33 hours, in 15 patients during transport to an intervention for up to 4 hours, and in 20 long-term ventilated patients at the medical intensive-care unit after insertion of a second tube intentionally into the esophagus with the help of a laryngoscope. The Colibri worked well in all groups investigated and showed no false results in the group with tubes inserted into the trachea and esophagus. Data suggest that the Colibri might serve as a valuable tool for evaluating and controlling tube position. This device is independent of power supply or electronic equipment, portable, small, and immediately ready for use.     

Cognitive impairment and associations with structural brain networks,endocrine status,and risk genotypes in newly orchiectomized testicular cancer patients

Brain Imaging and Behavior - A higher incidence of cognitive impairment (CI) has previously been reported among orchiectomized testicular cancer patients (TCPs), but little is known about the...     

Congenital left ventricular diverticulum: A rare cause of cardiac arrhythmia

Congenital left ventricular diverticula are rare cardiac malformations that usually remain asymptomatic. However, life-threatening complications as ventricular arrhythmias, systemic embolism, spontaneous rupture and development of valvular regurgitation, are described. Diagnosis is based on excluding coronary artery disease, traumatic or inflammatory causes, and other underlying cardiomyopathies. Treatment is directed towards the potential complications, yielding mainly therapy of ventricular arrhythmia. Surgical resection is required for larger-sized congenital aneurysms with adverse hemodynamic effects. We present two cases of a left ventricular diverticulum causing cardiac arrhythmia which led to further surgical treatment.