Phase I clinical evaluation of citrate-coated monocrystalline very small superparamagnetic iron oxide particles as a new contrast medium for magnetic resonance imaging

RATIONALE AND OBJECTIVES: To evaluate the safety and pharmacokinetics of a newly developed MR contrast medium consisting of very small superparamagnetic iron oxide particles (VSOP) coated with citrate (VSOP-C184) in a clinical phase I trial. METHODS: A total of 18 healthy subjects received either VSOP-C184 (core diameter: 4 nm; total diameter: 7 +/- 0.15 nm; relaxivities in water at 0.47 T (T1) 18.7 and (T2) 30 L/(mmol*seconds)) at doses of 0.015, 0.045, or 0.075 mmol Fe/kg (n = 5 per dose) or placebo (n = 1 per dose) as intravenous injections. Physical status and vital parameters were recorded, blood samples were collected for clinical chemistry and relaxometry (0.94 T), and urinalyses were performed before and for up to 2 weeks after administration. RESULTS: No serious adverse events occurred. The most pronounced adverse events occurred in 2 subjects of the highest dose group 45-50 minutes after injection. These were a drop in blood pressure and a drop in oxygen saturation, which were considered to be possibly drug-related and rapidly resolved without medication. Otherwise, no relevant changes in vital and laboratory parameters were observed. The parameters of iron metabolism exhibited short-term, dose-related changes. The injection of VSOP-C184 decreased T1 relaxation time of blood below 100 milliseconds for 18 minutes after a dose of 0.045 mmol [corrected] Fe/kg and for 60 minutes after 0.075 mmol [corrected] Fe/kg. CONCLUSIONS: The favorable data on the safety, tolerability, and efficacy of VSOP-C184 justify further clinical phase II and III trials as a contrast medium for MRI.     

Marijuana use and epilepsy: prevalence in patients of a tertiary care epilepsy center

The authors sought to determine the prevalence of marijuana use in patients with epilepsy by performing a telephone survey in a tertiary care epilepsy center. Twenty-one percent of subjects had used marijuana in the past year with the majority of active users reporting beneficial effects on seizures. Twenty-four percent of all subjects believed marijuana was an effective therapy for epilepsy. Despite limited evidence of efficacy, many patients with epilepsy believe marijuana is an effective therapy for epilepsy and are actively using it.     

One good turn deserves another: an event-related brain potential study of rotated mirror-normal letter discriminations

The time to decide if a letter is normal or backwards (mirror-reversed) increases as the letter is rotated away from the upright. It is widely accepted that this increase in time reflects the mental rotation of the stimulus to the upright orientation in order to determine the mirror-normal status of the stimulus. Although response times tend to be longer for mirrored stimuli than for normal stimuli, the difference is constant across orientation. Little work has been focused on why mirror-image stimuli produce longer response times than normal stimuli. This study examines the question of whether or not mirrored stimuli are rotated in the picture plane at the same time as normal stimuli, and if so, why response times to mirrored stimuli are longer than that for normal stimuli. Both the behavioural and electrophysiological findings suggest that the mirrored stimuli are not only rotated in the picture plane, but that they are subsequently rotated to the normal view. It is this additional rotation that produces, at least in part, the delayed response times for mirror-image stimuli.     

Hair diseases in childhood

This paper focuses on four important hair diseases mainly occurring in children. Trichotillomania is the most relevant differential diagnosis of alopecia areata in childhood. Meticulous inspection and lack of telogen hairs in the trichogram from the margin of the lesion usually are sufficient for differentiation. The trichogram also plays a significant role for the diagnosis of the loose anagen hair (loose anagen syndrome), a fairly new, but not rare entity, especially in distinguishing it from telogen effluvium. Five different types of clinical presentation are distinguished in tinea capitis. For the necessary systemic therapy; the new antimycotics terbinafine and itraconazole represent good alternatives to the well-tried griseofulvin. Several effective therapeutic options are also available for head lice, the most frequent parasitary infestation of school age. However, because of its neurotoxicity and the increasing problem of lice resistance lindane should not be used any longer for the treatment of head lice.     

Stellenwert der Magnetresonanztomographie für Indikationsstellung, Interventionsplanung und Nachsorge bei transarterieller Embolisationsbehandlung des Uterus myomatosus

ZusammenfassungZielsetzung Darstellung des Stellenwerts der Magnetresonanztomographie für die Indikationsstellung, Interventionsplanung und Nachsorge bei der transarteriellen Embolisationsbehandlung des symptomatischen Uterus myomatosus unter Berücksichtigung der aktuellen Literatur sowie eigener Ergebnisse.Material und Methodik Retrospektive Auswertung der MRT-Untersuchungen vor und nach Myomembolisation eines Kollektivs von 130 Patientinnen. Darlegung charakteristischer kernspintomographischer Bildbefunde und ihrer Bedeutung für die Indikationsstellung, Durchführung und Nachsorge. Einordnung der Ergebnisse in Zusammenschau mit der Literatur.Ergebnisse Die in der Literatur mitgeteilten mittelfristigen Ergebnisse zeigen eine Erfolgsrate des Verfahrens mit Verbesserung myombedingter Beschwerden in 82–94% und Größenreduktion der Myomknoten um durchschnittlich 36–64%. Typische Degenerationsformen von Leiomyomen des Uterus sowie das kernspintomographische Erscheinungsbild relevanter Differenzialdiagnosen werden exemplarisch dargestellt. Die für die Indikationsstellung relevanten Informationen zu Lage, Größe und Zahl der Myomknoten lassen sich kernspintomographisch sicher erheben. Eine Auswertung von 60 Patientinnen des Kollektivs zeigte in 16% der Fälle solitäre Leiomyome. In 47% der Fälle lagen 2–10 Myomknoten und in 37% mehr als 10 Leiomyome vor. Suberserös gestielte Leiomyome stellen eine Kontraindikation des Verfahrens dar und fanden sich in 5% der Fälle. Die MR-Angiographie erwies sich als vorteilhaft zur präinterventionellen Abklärung der pelvinen Gefäßanatomie und kann Kollateralen der Uterusversorgung nachweisen. Kontrastmittelunterstützte Aufnahmen eignen sich zur Kontrolle der erfolgreichen Devaskularisation nach Myomembolisation sowie zur Abklärung von Komplikationen.

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Modern imaging modalities in renal disease: CT and MRI

Considerable technical advances have been made in computed tomography (CT) and magnetic resonance imaging (MRI) over the last 10 years. Both modalities allow for high-resolution imaging of the entire abdomen before as well as during the arterial and parenchymal perfusion phase after intravenous contrast medium administration. Multiplanar reconstructions of the three-dimensional source data sets yield views in any spatial orientation. Maximum intensity projections enable the generation of CT or MR angiographies as well as CT or MR urographies from delayed images. Thus, both modalities today allow for comprehensive diagnostic evaluation of renal disease by a single examination comprising detailed visualization of the parenchyma as well as of arterial and venous vessels and assessment of excretion. CT and MRI thus enable efficient preoperative diagnostic assessment in particular in patients with renal masses.     

Effect of partial left ventriculectomy on left and right ventricular volumes and function as assessed with electron beam tomography: preliminary results

Our objective was to determine if left ventricular reduction surgery affects left and right ventricular volumes and function. Twenty-three patients with end-stage heart failure underwent contrast-enhanced electron beam tomographic function studies before and twice after partial left ventriculectomy (PLV). The PLV was combined with other cardiosurgical procedures in 20 of 23 patients. Left and right ventricular enddiastolic volume (LVEDV, RVEDV), stroke volume (LVSV, RVSV), ejection fraction (LVEF, RVEF), and enddiastolic diameter (LVEDD, RVEDD) were determined by manual tracing of endo- and epicardial borders at enddiastole and endsystole. Patients were scanned 31 days (±34) before and 18 days (±13) and 8 months (±4) after PLV. Mean pre- and early and late postoperative values for LVEDV, LVSV, LVEF, and LVEDD were 387.9 ml (±125.5 ml), 255.6 ml (±79.3 ml; p<0.01), and 253.7 ml (±97.8 ml; p<0.05), 79.7 ml (±25.2 ml), 74.8 ml (±17.9; n.s.), and 79.1 ml (±26.5 ml; n.s.), 21.6% (±7.3%), 31.9% (±13.4%; p<0.05), and 34.1% (±14.1%; p<0.05), and 72.0 mm (±10.6 mm), 64.3 mm (±8.5 mm; p<0.05), and 63.5 mm (±9.4 mm; p<0.05), respectively. Mean pre- and postoperative values for RVEDV, RVSV, RVEF, and RVEDD were 177.7 ml (±72.8 ml), 172.4 ml (±59.2 ml; n.s.), and 178.9 ml (±60.8 ml; n.s.), 60.3 ml (±21.6 ml), 68.8 ml (±19.9 ml; n.s.), and 78.3 ml (±25.3 ml; n.s.), 38.1% (±15.4%), 43.7% (±16.3%; p<0.05), and 45.1% (±11.2%; n.s.), and 50.4 mm (±10.9 mm), 48.1 mm (±8.7 mm; n.s.), and 48.5 mm (±9.8 mm; n.s.), respectively. The PLV may induce a significant early reduction of left ventricular volumes and improvement of biventricular function; however, our results must be judged carefully as the majority of patients in this study underwent additional cardiosurgical procedures, the contributory effect of which on the overall outcome remains unclear. Electronic Publication     

Direct Evidence That Polysorbate-80-Coated Poly(Butylcyanoacrylate) Nanoparticles Deliver Drugs to the CNS via Specific Mechanisms Requiring Prior Binding of Drug to the Nanoparticles

Purpose. It has recently been suggested that the poly(butylcyanoacrylate) (PBCA) nanoparticle drug delivery system has a generalized toxic effect on the blood-brain barrier (BBB) (8) and that this effect forms the basis of an apparent enhanced drug delivery to the brain. The purpose of this study is to explore more fully the mechanism by which PBCA nanoparticles can deliver drugs to the brain. Methods. Both in vivo and in vitro methods have been applied to examine the possible toxic effects of PBCA nanoparticles and polysorbate-80 on cerebral endothelial cells. Human, bovine, and rat models have been used in this study. Results. In bovine primary cerebral endothelial cells, nontoxic levels of PBCA particles and polysorbate-80 did not increase paracellular transport of sucrose and inulin in the monolayers. Electron microscopic studies confirm cell viability. In vivo studies using the antinociceptive opioid peptide dalargin showed that both empty PBCA nanoparticles and polysorbate-80 did not allow dalargin to enter the brain in quantities sufficient to cause antinociception. Only dalargin preadsorbed to PBCA nanoparticles was able to induce an antinociceptive effect in the animals. Conclusion. At concentrations of PBCA nanoparticles and polysorbate-80 that achieve significant drug delivery to the brain, there is little in vivo or in vitro evidence to suggest that a generalized toxic effect on the BBB is the primary mechanism for drug delivery to the brain. The fact that dalargin has to be preadsorbed onto nanoparticles before it is effective in inducing antinociception suggests specific mechanisms of delivery to the CNS rather than a simple disruption of the BBB allowing a diffusional drug entry.     

Attention and emotion: an ERP analysis of facilitated emotional stimulus processing

Recent event-related potential studies observed an early posterior negativity (EPN) reflecting facilitated processing of emotional images. The present study explored if the facilitated processing of emotional pictures is sustained while subjects perform an explicit non-emotional attention task. EEG was recorded from 129 channels while subjects viewed a rapid continuous stream of images containing emotional pictures as well as task-related checkerboard images. As expected, explicit selective attention to target images elicited large P3 waves. Interestingly, emotional stimuli guided stimulus-driven selective encoding as reflected by augmented EPN amplitudes to emotional stimuli, in particular to stimuli of evolutionary significance (erotic contents, mutilations, and threat). These data demonstrate the selective encoding of emotional stimuli while top-down attentional control was directed towards non-emotional target stimuli.