Apallisches Syndrom nach Abruptio bei Sichelzellanämie

Zusammenfassung Eine 20 Jahre alt gewordene, klinisch unauffällige Patientin aus Togo unterzog sich einer Abruptio in der 6. Schwangerschaftswoche unter Allgemeinanästhesie. Während der Narkoseausleitung kam es zum Herzstillstand und in der Folgezeit zur Entwicklung eines apallischen Syndroms mit Todeseintritt nach 1 Jahr und 9 Monaten. Erst nach dem Eingriff wurde eine Sichelzellanämie (HbS/S) diagnostiziert. Nach Vorstellung der Obduktionsbefunde werden ausgewählte gutachterliche Fragen sowie der Stellenwert von Leitlinien bei Behandlungsfehlergutachten diskutiert.

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Gadobutrol-enhanced moving-table magnetic resonance angiography in patients with peripheral vascular disease: a prospective,multi-centre blinded comparison with digital subtraction angiography

The purpose of this study was to compare moving-table three-dimensional contrast-enhanced magnetic resonance angiography (CE MRA), using 1.0-mol gadobutrol, with intra-arterial digital subtraction angiography (i.a. DSA) for evaluation of pelvic and peripheral arteries in patients with peripheral arterial occlusive disease. A total of 203 patients were examined in a prospective, multi-centre study at 1.0/1.5 T. Ten vessel segments of one leg were evaluated on-site and by three independent blinded reviewers off-site. One hundred eighty-two patients were evaluable in blinded reading. For pelvis and thigh, there was statistically significant diagnostic agreement between CE MRA and i.a. DSA on-site (94%) and off-site (86-88%). Overall, for detection of clinically significant stenoses, 93% sensitivity and 90% specificity were achieved in on-site evaluation, with 71-76 and 87-93% off-site; for detection of occlusion, sensitivity and specificity on-site were 91 and 97%, with 75-82 and 94-98% off-site. Evaluation was more sensitive on-site than off-site for detection of stenoses and occlusion, whereas specificity was similar. The CE MRA with 1.0-mol gadobutrol gave results comparable to those of i.a. DSA for the larger arteries of pelvis and thigh. Results for calf arteries were compromised by spatial resolution and technical limitations.     

Safety of contrast-enhanced MR angiography employing gadobutrol 1.0 M as contrast material

Our objectives were to evaluate the safety of intravenous 1.0-M gadobutrol injections in patients with an indication for contrast-enhanced magnetic resonance angiography (CE MRA) of supra-aortal, pelvic, or peripheral arteries by examining and assessing adverse events, laboratory values, vital signs and ECG findings for clinical significance. In 435 patients, recruited in three multicenter trials for safety evaluations of the new contrast agent 1.0-M gadobutrol, CE MRA was performed with 1.0- to 1.5-T scanners using three-dimensional gradient-echo sequences and phased-array coils. The study population comprised 312 men and 123 women with a mean age of 60.9 years. Two hundred seven patients had an indication for imaging of body arteries and 228 had an indication for imaging of peripheral arteries. Blood laboratory values and urinalysis results of 124 patients as well as heart rate, blood pressure, and 12-lead-electrocardiogram readings of 93 patients obtained during a follow-up period of up to 72 h after the injection of contrast media were available for safety analysis. Contrast media application was performed as intravenous bolus injection of 1.0-M gadobutrol in fixed doses according to the patients' body weight (b.w.) and indication for CE MRA and was followed by a 20- to 40-ml saline flush. Mean dose actually applied was 0.1 0.27 mmol/kg b.w. Flow rate ranged between 0.2 and 2.0 ml/s. Safety evaluations found a good tolerability with only 4.6% of at least "possibly related" adverse reactions and no clinically relevant changes in blood and urine samples including no transmetallation effect on serum zinc values. Analysis of renal tolerance showed no influence on renal function irrespective of preexisting renal impairment. The ECG analysis (rhythm analysis, pace-setting disturbances, conduction disturbances, and time interval measurements, including uncorrected and corrected QT) showed no clinically relevant effect of the injection of 1.0-M gadobutrol on the cardiac conduction system. Intravenous injection of 1.0-M gadobutrol at a dose of up to 0.1 0.27 mmol/kg b.w. in the indication CE MRA is safe and causes no clinically relevant changes in safety parameters such as heart rate, blood pressure, blood and urine laboratory values, and cardiac conduction system.     

T-cell receptor downregulation by ceramide-induced caspase activation and cleavage of the zeta chain

Regulation of T-cell receptor (TCR) cell surface expression levels is probably an important mechanism by which T-cell responsiveness is controlled. Previously, two distinct pathways for TCR downregulation have been described. One is dependent on protein kinase C (PKC) and the leucine-based receptor-sorting motif (L-based motif) of the CD3 gamma chain but independent of tyrosine kinases, whereas the other is dependent on the tyrosine kinase activation but independent of the PKC and the CD3 gamma L-based motif. In this study, we describe a new pathway for TCR downregulation distinct from both the PKC/CD3 gamma L-based motif-dependent and the tyrosine kinase-dependent pathways. This pathway is dependent on ceramide-induced activation of caspases and correlate with caspase-mediated cleavage of the zeta chain. Thus, a 10--15% downregulation of the TCR was induced following the treatment of the T cells with ceramide for 4 h. A close correlation between TCR downregulation, caspase activation, and cleavage of the zeta chain was found. Furthermore, the caspase inhibitors abolished the cleavage of the zeta chain and TCR downregulation in parallel with the inhibition of the caspase activity.     

Image analysis and Sheimpflug photography of anterior segment of the eye--a review

BACKGROUND: Light scattering properties of the cornea and lens change in relation to age. This process is influenced by noxious factors which may induce the formation of cataracts. Four different camera types based on the Scheimpflug principle have been developed for documentation and evaluation of light scattering in the eye. Topcon SL-45. Zeiss SLC, Oxford CASE 2000, Nidek EAS 1000. Only the SL-45 and EAS 1000, however, have found a wider application in clinical and experimental studies. MATERIAL AND METHODS: Documentation of the eye with a Scheimpflug system is performed in a dark room after mydriasis induction. The rotating axis of the camera is aligned to the optical axis of the eye with fixation devices. Four meridians have been found appropriate for routine documentation. Image analysis is based on peak height and distance evaluation of 2 layers in the cornea and 10 layers in the lens. Standardization devices allow correction of technical differences in the recording process. RESULTS: Evaluation of the ageing properties of the lens has evidenced typical density developments for each individual layer, the cortex increasing in density earlier than the nucleus. Cataract classification using a Scheimpflug camera provides an objective characterization of cataract type and progression. The outcome of surgical procedures changing the refractive power of the eye can be evaluated with a Scheimpflug camera as well. Its application in studies dealing with the ocular effects of Quinolones and HMG-CoA-reductase inhibitors, has demonstrated that Scheimpflug photography is the method of choice for establishment of a safety profile for a new drug. CONCLUSIONS: Scheimpflug photography has proven to be ideal for objective documentation of the anterior eye segment in human and animal eyes, although both documentation and image analysis demand technical expertise to be reproducible.     

Light scattering in normal and cataractous lenses of farmed Atlantic salmon (Salmo salar): a slit lamp and Scheimpflug photographic study

To investigate normal light scattering and cataract formation, the anterior eye segments of farmed Atlantic salmon (Salmo salar) reared in fresh water and sea water were documented in vivo for the first time with a Topcon SL-45 Scheimpflug camera. A total of 40 fish from the fresh-water-rearing period, obtained from 2 groups of identical age but showing a different growth rate, and 24 fish from the sea-water-rearing period, sampled from 2 groups with identical age but being fed different food brands, were included in this study. The fish were anaesthetized before examination. Due to the naturally wide pupil, no mydriatic compound was applied. All fish were removed from the water for photography, which was performed for each eye in 0 degrees = vertical slit position. Images were recorded on Kodak Tmax 400 black-and-white film. Microdensitometric image analysis of all negatives was performed using a Joyce-Loebl online microdensitometer. In spite of the virtual absence of an anterior chamber gap between cornea and lens and very little light scattering in the normal fish lens, a small number of distinct layers could be reproducibly identified in the lens. While there was little abnormal light scattering which could point to cataract development in young fish from the fresh water period, the evaluation of the lenses from the 2 sea water groups showed the presence of specific forms of cataract especially in the cortical and supranuclear layers. There were significant differences between the groups fed different food brands at the sea water site. In conclusion, Scheimpflug photography proved to be applicable to eye research in fish in vivo. It is suggested that this method should be employed for reproducible documentation as an extension to slit lamp monitoring in experimental research to reveal causative factors for cataracts in farmed fish.     

Nitric oxide modulates lithium-induced conditioned taste aversion

Nitric oxide (NO) has been shown to affect the behaviour in animal models of depression, anxiety and avoidance learning. Lithium has marked effect in avoidance learning, an effect that can be modulated via the 5-HT system. Experiments were carried out using the conditioned taste aversion (CTA) paradigm to investigate whether administration of NO-modifying drugs, serotonergic drugs and lithium, alone or in combination, induced or affected a CTA. The NO-precursor L-arginine (L-Arg), the non-specific inhibitor of NOS and guanylate cyclase, methylene blue (MB) and the specific NOS inhibitor 7-Nitroindazole (7-NI) all produced CTAs in a dose-dependent fashion. Furthermore, we found that L-Arg counteracted the CTAs induced by LiCl or MB but failed to modulate the CTA produced by 7-NI. The administration of the selective 5-HT1A agonist, 8-OH-DPAT, counteracted the CTAs produced by MB and 7-NI. In contrast, depletion of 5-HT by p-Chlorophenylalanine did not affect the aversions produced by MB and 7-NI, but counteracted the CTA produced by L-Arg. Our results suggest that NO plays a role in the acquisition of the CTA induced by LiCl. Furthermore, the results suggest that the 5-HT1A receptor plays an important role in the CTA induced by MB and 7-NI, thus indicating a possible interaction between the 5-HT and NO systems.     

Bilateral deep venous thrombosis in protein S deficiency. Detection by radionuclide venography

Patients with primary hypercoagulopathies often present with recurrent, spontaneous deep venous thrombosis and pulmonary embolism. An adolescent eventually diagnosed with protein S deficiency presented with unilateral deep venous thrombosis documented ultrasonographically. Scintigraphic studies showed no evidence of pulmonary embolism but revealed a complete absence of deep venous flow in both lower extremities, the pelvis, and the abdomen. Subsequent ultrasonography and CT scanning documented this marked thrombotic extension. Radionuclide scintigraphy may play an important role in the serial evaluation of primary hypercoagulable states, particularly when pulmonary scintigraphy is combined with bilateral, lower extremity venography.