The recently identified transport proteins organic cation transporter 1 (OCT1), OCT2, and extraneuronal monoamine transporter (EMT) accept dopamine, noradrenaline, adrenaline, and 5-hydroxytryptamine as substrates and hence qualify as non-neuronal monoamine transporters. In the present study, selective transport substrates were identified that allow, by analogy to receptor agonists, functional discrimination of these transporters. To contrast efficiency of solute transport, stably transfected 293 cell lines, each expressing a single transporter, were examined side by side in uptake experiments with radiolabeled substrates. Normalized uptake rates indicate that tetraethylammonium, with a rate of about 0.5 relative to 1-methyl-4-phenylpyridinium (MPP+), is a good substrate for OCT1 and OCT2. It was not, however, accepted as substrate by EMT. Choline was transported exclusively by OCT1, with a rate of about 0.5 relative to MPP+. Histamine was a good substrate with a rate of about 0.6 relative to MPP+ for OCT2 and EMT, but was not transported by OCT1. Guanidine was an excellent substrate for OCT2, with a rate as high as that of MPP+. Transport of guanidine by OCT1 was low, and transport by EMT was negligible. With the guanidine derivatives cimetidine and creatinine, a pattern strikingly similar to guanidine was observed. Collectively, these substrates reveal key differences in solute recognition and turnover and thus challenge the concept of "polyspecific" organic cation transporters. In addition, our data, when compared with previous studies, suggest that OCT2 corresponds to the organic cation/H+ antiport mechanism in renal brush-border membrane vesicles, and that EMT corresponds to the guanidine/H+ antiport mechanism in membrane vesicles from placenta and intestine.

The recently cloned apical renal transport system for organic cations (OCT2) exists in dopamine-rich tissues such as kidney and some brain areas (Grü ndemann, D., Babin-Ebell, J., Martel, F., Ö rding, N., Schmidt, A., and Schö mig, E.

IntroductionTranspulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000™ system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO™ method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: NCT01405040)MethodsSeventy-two critically ill patients with clinical indication for advanced hemodynamic monitoring were included in this prospective, multicenter, observational study. During a 72-hour observation period, 443 sets of thermodilution measurements were performed with the new system. These measurements were electronically recorded, converted into an analog resistance signal and then re-analyzed by a PiCCO2™ device (Pulsion Medical Systems SE).ResultsFor CO, GEDV, and EVLW, the systems showed a high correlation (r2 = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2 L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and 12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%, 95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO, GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV measurements was significantly better using the VolumeView™ algorithm compared to the PiCCO™ algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile range), P = 0.000049).ConclusionsFor CO, GEDV, and EVLW, the agreement of both the individual measurements as well as measurements of change showed the interchangeability of the two methods. For the VolumeView method, the higher precision may indicate a more robust GEDV algorithm.Trial registrationclinicaltrials.gov NCT01405040.

This phase I study tested the safety, feasibility, pharmacokinetics and pharmacodynamics of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion (HIPEC) in patients with platinum-sensitive recurrent epithelial ovarian cancer (EOC) undergoing secondary cytoreductive surgery followed by postoperative platinum-based intravenous chemotherapy. Twelve patients with operable, recurrent platinum-sensitive EOC (recurrence !6 months after first-line therapy) were included according to the classical 313 dose-escalation design at three dose levels-60, 80 and 100 mg=m 2 . After surgical cytoreduction, a single dose of cisplatin was administered via HIPEC for 90 min at 41-43 C. Postoperatively, all patients were treated with standard intravenous platinum-based combination chemotherapy. One of six patients experienced a dose-limiting toxicity (grade 3 renal toxicity) at a dose of 100 mg=m 2 . The remaining five patients treated with 100 mg=m 2 tolerated their treatment well. The recommended phase II dose was established at 100 mg=m 2 . The mean peritoneal-to-plasma AUC ratio was 19Á5 at the highest dose level. Cisplatin-induced DNA adducts were confirmed in tumor samples. Common postoperative grade 1-3 toxicities included fatigue, postoperative pain, nausea, and surgical site infection. The ability to administer standard intravenous platinum-based chemotherapy after HIPEC was uncompromised. Cisplatin administered as HIPEC at a dose of 100 mg=m 2 has an acceptable safety profile in selected patients undergoing secondary cytoreductive surgery for platinumsensitive recurrent EOC. Favorable pharmacokinetic and pharmacodynamic properties of HIPEC with cisplatin were confirmed at all dose levels, especially at 100 mg=m 2 . The results are encouraging to determine the efficacy of HIPEC as a complementary treatment in patients with EOC.

The performance of the new VolumeView™-CCO method is as reliable as the PiCCO2™-CCO pulse wave analysis in critically ill patients. However, an improved precision was observed with the VolumeView™ technique. CLINICALTRIALS.GOV IDENTIFIER: NCT01405040.

Background: There is controversy as to whether performing a total or subtotal colectomy is justified in patients with advanced ovarian cancer, given its potential for morbidity and a negative effect on long-term quality of life. The aim of this study was to assess the perioperative complications, mortality and outcomes of patients who underwent total or subtotal colectomy as part of the surgical procedure for primary or recurrent epithelial ovarian cancer. Patients and Methods: All patients who had undergone surgery including a total or subtotal colectomy for advanced or recurrent ovarian cancer between 2005 and 2013 at our institution were retrospectively identified. Results: In this time period, 339 patients underwent surgery for epithelial ovarian cancer, which in 11 (3%) patients included a total or subtotal colectomy. Severe grade 3-4 postoperative complications occurred in 3 (27%) patients, and 1 (9%) patient died within 60 days of surgery. Conclusion: A total or subtotal colectomy is associated with increased but acceptable morbidity in selected patients undergoing primary cytoreductive surgery. However, in the recurrent/palliative setting, total or subtotal colectomy should be avoided as the prognosis is poor and the morbidity outweighs the clinical benefit.

Target-controlled infusion (TCI) incorporates the pharmacokinetic variables of an IV drug to facilitate safe and reliable administration. In this clinical study we investigated the performance of propofol TCI in combination with remifentanil. Fifty-four adult patients scheduled for general surgery lasting longer than 1 h received a combined TCI of propofol (Marsh parameter set; propofol randomly either dissolved with long- or middle-/long-chain triglycerides) and remifentanil. Arterial propofol plasma concentrations and hemodynamic and derived electroencephalogram variables were determined at various stages before, during, and after surgery. Measured propofol plasma concentrations exceeded the predicted values by 59%, and 48% when recalculated with the Schnider parameter set. Pharmacokinetic population analysis showed a small central volume of distribution (3.55 L) and reduced clearance (1.31 L/min) for propofol. ASA status and sex were the only variables that had a significant influence on propofol pharmacokinetics. In a second step, a new pharmacokinetic variable set for propofol was determined in the first 27 patients. Post hoc performance analysis of the remaining 27 patients showed improved accuracy using the new variable set. Our results show that when remifentanil and propofol are combined, the Marsh and Schnider parameter sets systematically underestimate propofol plasma concentrations. Presented, in part, at the Annual Meeting of the European Society of Anesthesiologists, Amsterdam, The Netherlands, June 1, 1999, and the Annual Meeting of the American Society of Anesthesiologists, Dallas, Texas, October 12, 1999.

Improvement of the display of information in the operating room is warranted, and recent developments are promising. However, their introduction into mass market is not yet on the horizon, although the shortcomings of the traditional single-sensor-single-indicator principle are known for a long time. If manufacturers are reluctant to implement new techniques into their devices, they should at least facilitate access to monitoring raw data in order to allow independent development of displays.