A case of acute optic neuritis during pregnancy treated by membrane-based therapeutic plasma exchanges without systemic anticoagulation.

INTRODUCTION: In acute optic neuritis, high dose steroid therapy as first - line treatment is contraindicated in early pregnancy, therapeutic plasma exchanges (TPE) represent an alternative. We report a case of a pregnant woman with progressive, acute optic neuritis subjected to membrane-based therapeutic plasma exchange with extracorporal citrate-based anticoagulation. CASE PRESENTATION: A 35 year-old second-time pregnant woman (4th week of gravidity) of Caucasian ethnicity complained of visual impairment of the right eye. She was hospitalized for suspected optic neuritis. In the eye exam central and peripheral scotoma of the right side were found. T2 weighted Magnetic-Resonance Imaging revealed an isolated, prechiasmal lesion of the right optic nerve, and the patient had a delayed p100 latency of visually evoked potentials of the right eye. Cerebrospinal-fluid investigation was unrevealing. The diagnosis of right sided optic neuritis was established. Due to early pregnancy, steroids were contraindicated. Visual disturbances further deteriorated by day 2 in hospital. For therapy, 5 sessions of membrane-based therapeutic plasma exchange with albumin solution were performed. An extracorporal anticoagulation using citrate with calcium substitution was applied. After the second session, there was a subjective improvement of symptoms. At discharge on day 14, visual acuity was no longer impaired, sensitivity to bright light remained. In eye exam at 3.5 months after discharge, the patient ha d a complete recovery. Follow-up gynecological exams were unrevealing. CONCLUSION: This case of unilateral acute optic neuritis supports the view that membrane-based therpautic plasma exchange without systemic anticoagulation represents a safe intervention in pregnancy.

Sorafenib in platinum-treated patients with extensive stage small cell lung cancer: a Southwest Oncology Group (SWOG 0435) phase II trial.

INTRODUCTION: Sorafenib is a multikinase inhibitor affecting pathways involved in tumor progression and angiogenesis. We conducted a phase II trial of sorafenib in platinum-treated patients with extensive stage small cell lung cancer to determine the tumor response rate, toxicity, and overall survival. METHODS: Patients with histologically confirmed, measurable disease, Zubrod performance status 0 to 1, and no more than 1 prior platinum-based treatment were eligible. Patients were stratified by platinum-sensitivity status: sensitive (progression >90 days after platinum) or refractory (progression during or ≤90 days after platinum). Patients were treated with sorafenib 400 mg orally twice a day continuously on a 28-day cycle. RESULTS: Of 89 patients registered, 82 were evaluable for toxicity assessment, and 83 were evaluable for response. There were four partial responses seen among the 38 patients in the platinum-sensitive stratum, for an estimated response rate of 11% (95% confidence interval: 3-25%), and one partial response among the 45 patients in the platinum-refractory stratum, for an estimated response rate of 2% (95% confidence interval: 0-12%). The median overall survival estimates were 6.7 months (95% confidence interval: 6.1-9.1 months) for the platinum-sensitive stratum and 5.3 months (95% confidence interval: 3.3-7.5 months) in the platinum-refractory stratum. Nineteen patients discontinued treatment because of adverse events or side effects from therapy. CONCLUSIONS: Based on the lack of disease control seen in our trial, further investigation of single-agent sorafenib in the small cell lung cancer population is not recommended. Combination trials of sorafenib and chemotherapy are ongoing.

Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture.

The use of human embryonic stem cells (hESCs) as a source of dopaminergic neurons for Parkinson's disease cell therapy will require the development of simple and reliable cell differentiation protocols. The use of cell cocultures, added extracellular signaling factors, or transgenic approaches to drive hESC differentiation could lead to additional regulatory as well as cell production delays for these therapies. Because the neuronal cell lineage seems to require limited or no signaling for its formation, we tested the ability of hESCs to differentiate to form dopamine-producing neurons in a simple serum-free suspension culture system. BG01 and BG03 hESCs were differentiated as suspension aggregates, and neural progenitors and neurons were detectable after 2-4 weeks. Plated neurons responded appropriately to electrophysiological cues. This differentiation was inhibited by early exposure to bone morphogenic protein (BMP)-4, but a pulse of BMP-4 from days 5 to 9 caused induction of peripheral neuronal differentiation. Real-time polymerase chain reaction and whole-mount immunocytochemistry demonstrated the expression of multiple markers of the midbrain dopaminergic phenotype in serum-free differentiations. Neurons expressing tyrosine hydroxylase (TH) were killed by 6-hydroxydopamine (6-OHDA), a neurotoxic catecholamine. Upon plating, these cells released dopamine and other catecholamines in response to K+ depolarization. Surviving TH+ neurons, derived from the cells differentiated in serum-free suspension cultures, were detected 8 weeks after transplantation into 6-OHDA-lesioned rat brains. This work suggests that hESCs can differentiate in simple serum-free suspension cultures to produce the large number of cells required for transplantation studies.

[MR-guided laser-induced thermo-ablation of liver tumors: clinical experiences and therapy control concepts]. / MRT-gestützte laserinduzierte Thermoablation bei Lebertumoren--Klinische Aspekte und Konzept eines Uberwachungssystems.

Minimally-invasive, laser-induced interstitial thermotherapy (LITT) of solid tumors represents a valid alternative to surgical procedures such as tumor resections. Within the framework of a palliative study on 16 patients, a total of 25 metastases in the liver were treated in an open MR system (0.5 T). The intraoperative scanner design allows patient-based navigation, decisive for a safe applicator positioning, as well as temperature monitoring and direct inspection of the therapy result, without need for patient transfer or repositioning. Although the MR thermometry applied in the open scanner assisted LITT monitoring, the current accuracy of temperature data was not sufficient to serve automatic irradiation control. Therefore, an experimental monitoring and control system was developed in a closed MR scanner (1.5 T) featuring a calibrated MR thermometry. The system provides also an interface to the laser system, allowing the automatic off/on switching of the laser power according to preoperatively defined control criteria. The basic functionality of the automatic laser control was successfully demonstrated with laser ablation experiments of liver samples using irradiation parameters close to typical clinical values.