Monitoring the Reversibility of GPCR Signaling by Combining Photochromic Ligands with Label-free Impedance Analysis.

G protein-coupled cell surface receptors (GPCR) trigger complex intracellular signaling cascades upon agonist binding. Classic pharmacological assays provide information about binding affinities, activation or blockade at different stages of the signaling cascade, but real time dynamics and reversibility of these processes remain often disguised. We show that combining photochromic NPY receptor ligands, which can be toggled in their receptor activation ability by irradiation with light of different wavelengths, with whole cell label-free impedance assays allows observing the cell response to receptor activation and its reversibility over time. The concept demonstrated on NPY receptors may be well applicable to many other GPCRs providing a deeper insight into the time course of intracellular signaling processes.

Hepatic intraarterial chemotherapy with gemcitabine in patients with unresectable cholangiocarcinomas and liver metastases of pancreatic cancer: a clinical study on maximum tolerable dose and treatment efficacy.

PURPOSE: To define the maximum tolerated dose (MTD) of hepatic intraarterial chemotherapy with gemcitabine, administered with and without starch microspheres, in patients with inoperable intrahepatic cholangiocarcinomas and liver metastases of pancreatic carcinomas. METHODS: Gemcitabine was administered on days 1 and 8 with intervals of 2 weeks between the cycles. In group A the initial gemcitabine dose of 1,000 mg/m(2) (without microspheres) was increased in 200-mg/m(2) steps up to a maximum dose of 2,000 mg/m(2). In group B the MTD with microspheres was assessed by giving an additional microsphere dose according to tumor extent and body weight, increasing gemcitabine starting from a dose-step below the MTD with microspheres. The MTD was evaluated via clinical and laboratory findings. RESULTS: Twenty-four patients were enrolled (12 males, 12 females, mean age 59.17 years; intrahepatic cholangiocarcinoma: n = 17, liver metastases of pancreatic carcinoma: n = 7). The MTD of gemcitabine without microspheres was reached at 1,400 mg/m(2), and of gemcitabine with microspheres at 1,800 mg/m(2). The comparative evaluation revealed statistically significant better data for the time to progression (p < 0.01) and survival for the group with microspheres (6.8 and 20.2 months) in comparison to the group without microspheres (4.2 and 13.5 months). CONCLUSION: This clinical study indicates that the intraarterial application of gemcitabine with doses higher than the recommended 1,000 mg/m(2) is well tolerated if combined with microspheres, and yields respectable results in patients who do not respond to systemic chemotherapy.

Clinical impact of MRI in acute wrist fractures.

The purpose of this study was to evaluate the clinical impact of MRI in the early diagnosis of wrist trauma. High-resolution MR imaging was performed on a 1.5-T unit (Symphony Quantum, Siemens, Erlangen, Germany) using coronal and axial T1- and T2-weighted fat-saturated turbo-spin-echo sequence via a dedicated wrist coil within a mean of 6.6 days after initial radiographs in 54 patients (56 wrists) with clinical suspicion of wrist fractures and normal plain or indistinct radiographs. Initial radiographs were evaluated independently by two senior radiologists and the hand surgeon without knowledge of the MRI findings. The initial treatment protocol was based on evaluation of plain films and clinical findings by the hand surgeon. Treatment protocol was changed after MRI examination if necessary. In 31 of 56 wrists MRI findings resulted in a change of diagnosis. There were false-positive diagnoses on plain radiographs in nearly one half ( n=25) of the patients. False-negative diagnoses on plain radiographs resulted in 6 cases. Magnetic resonance imaging detected additional injuries of soft tissue in more than one third ( n=20). In 22 of 56 wrists the period of immobilization could be shortened or ended, in 12 of 56 it was prolonged, and in 3 of 56 a surgical intervention was necessary. In 19 wrists MRI had no therapeutic consequences. Our data demonstrate the high clinical impact of MRI in the detection of acute wrist fractures. We recommend MRI of the wrist immediately on the day of trauma if there is clinical suspicion and normal plain radiographs. Accurate diagnosis by MRI examination within the first days following trauma may reduce economic costs due to shortened immobilization time in cases with a suspected fracture but plain radiographs.

MR-guided laser-induced thermotherapy with a cooled power laser system: a case report of a patient with a recurrent carcinoid metastasis in the breast.

We report a case of a 52-year-old woman with a palpable recurrent metastasis of a neuroendocrine carcinoma to the upper outer quadrant of the right breast. For the treatment of this lesion, MR-guided laser-induced thermotherapy was performed with a cooled power laser system (Nd:YAG-Laser). An open 0.2-T MR unit was used for the monitoring of the laser energy delivery to the breast; thus, a thermosensitive fast low-angle shot 2D sequence for MR thermometry was used, so the ablation of the tumor and the increase of laser-induced necrosis could be interactively visualized with the repetitive use of this sequence. The postinterventional MR control exams 1 day and 4 months after laser-induced thermotherapy at the 1.5-T MR unit (Magnetom Symphony Quantum, Siemens, Erlangen, Germany) verified the complete ablation of the tumor without any signs of residual or relapsing tumor.