Search results for "Maxim"

Phase I Pharmacokinetic/Pharmacodynamic Study of MLN8237, an Investigational, Oral, Selective Aurora A Kinase Inhibitor, in Patients with Advanced So…

2012

Abstract Purpose: Aurora A kinase (AAK) is a key regulator of mitosis and a target for anticancer drug development. This phase I study investigated the safety, pharmacokinetics, and pharmacodynamics of MLN8237 (alisertib), an investigational, oral, selective AAK inhibitor, in 59 adults with advanced solid tumors. Experimental Design: Patients received MLN8237 once daily or twice daily for 7, 14, or 21 consecutive days, followed by 14 days recovery, in 21-, 28-, or 35-day cycles. Dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) for the 7- and 21-day schedules were determined. Pharmacokinetic parameters were derived from plasma concentration–time profiles. AAK inhibition in…

Phase I Pharmacokinetic and Pharmacodynamic Dose-Escalation Study of RG7160 (GA201), the First Glycoengineered Monoclonal Antibody Against the Epider…

2011

Purpose We conducted a phase I dose-escalation study to characterize the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic properties of RG7160 (GA201), a humanized and glycoengineered immunoglobulin G1 anti–epidermal growth factor receptor (EGFR) monoclonal antibody with enhanced antibody-dependent cell-mediated cytotoxicity. Patients and Methods Seventy-five patients with advanced EGFR-positive solid tumors received RG7160 (50 to 1,400 mg) administered every week, every 2 weeks, or every 3 weeks. Dose escalation followed a three-plus-three trial design. Results No maximum-tolerated dose was reached for any dosing schedule. Common adverse events (AEs) included rash (80% of patien…

Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence

2005

BACKGROUND In this study, the authors analyzed the efficacy and safety of gemtuzumab ozogamicin (GO) (Mylotarg®), an antibody-targeted chemotherapy for CD33-positive acute myeloid leukemia (AML). METHODS Patients with CD33-positive AML in first recurrence were entered in 3 open-label, single-arm, Phase II studies. Patients received monotherapy with GO 9 mg/m2 as a 2-hour intravenous infusion in 2 doses separated by 2 weeks. Patients were evaluated for remission, survival, and treatment-emergent adverse events. RESULTS Two hundred seventy-seven patients (median age, 61 yrs) were treated with GO, and 71 patients (26%) achieved remission, which was defined as ≤ 5% blasts in the bone marrow wit…

A phase I dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours.

2012

Abstract Background EMD 521873 (Selectikine), an immunocytokine comprising a DNA-targeting antibody, aimed at tumour necrosis, fused with a genetically modified interleukin-2 (IL-2) moiety, was investigated in this first-in-human phase I study. Methods Patients had metastatic or locally advanced solid tumours failing previous standard therapy. Selectikine was administered as a 1-hour intravenous infusion on 3 consecutive days, every 3weeks. A subgroup of patients also received 300mg/m 2 cyclophosphamide on day 1 of each cycle. Escalating doses of Selectikine were investigated with the primary objective of determining the maximum tolerated dose (MTD). Results Thirty-nine patients were treate…

Accuracy of check-bite registration and centric condylar position

2002

In a dentate subject a jaw relation can either be determined in maximum intercuspation and is as such given by the occlusal morphology, or the mandibular position can be allocated according to the centric position of the condyles. For comprehensive restorative treatment or analytic measures of the occlusion it is important to record the centric condylar position. Various registration methods have been described in the literature, but there is no consensus on which is the 'best'. The aim of the present study was therefore to assess the accuracy of various registration methods and evaluate a possible influence of the used materials. Four dentists were involved in the clinical part of the stud…

Functional impression and jaw registration: a single session procedure for the construction of complete dentures*

2004

The conventional fabrication of complete dentures involves two separate clinical sessions for functional impression making and jaw registration. The presented method combines both procedures in one session. The aim of this study was to survey the three-dimensional tooth positions in complete dentures with reference to the ridges to establish arbitrary guideline values that could be used for the manufacturing of tooth-position analogue plastic rims on functional impression trays. New complete dentures were fabricated by supervised undergraduate students in the conventional manner for 104 edentulous patients. The position of the maxillary teeth was surveyed in the horizontal plane using the S…

Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-fi…

2017

Myelodysplastic syndromes are characterised by ineffective erythropoiesis. Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF β) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy. We aimed to assess the safety and efficacy of luspatercept in patients with anaemia due to lower-risk myelodysplastic syndromes.In this phase 2, multicentre, open-label, dose-finding study (PACE-MDS), with long-term extension, eligible patients were aged 18 years or older, had International Prognostic Scoring System-defined low or intermediate 1 risk myelodysplastic syndromes or non-proliferative chronic myelomonocytic leuk…

Instantaneous transfer entropy for the study of cardio-respiratory dynamics

2015

Measures of transfer entropy have been proposed to quantify the directional coupling and strength between two complex physiological variables. Particular attention has been given to nonlinear interactions within cardiovascular and respiratory dynamics as influenced by the autonomic nervous system. However, standard transfer entropy estimates have shown major limitations in dealing with issues concerning stochastic system modeling, limited observations in time, and the assumption of stationarity of the considered physiological variables. Moreover, standard estimates are unable to track time-varying changes in nonlinear coupling with high resolution in time. Here, we propose a novel definitio…

Effects of a 21 days space flight on the mechanical performance and the EMG power spectrum of the leg muscles

2002

Effects of different electrical stimulation currents and phase durations on submaximal and maximum torque, efficiency, and discomfort: a randomized c…

2021

Abstract Background Neuromuscular electrical stimulation (NMES) is an important therapeutic tool for rehabilitation. However, best stimulation parameters remain to be determined. Objective To determine the influence of different electrical stimulation currents and phase durations on torque, efficiency, and discomfort. Methods Using a cross-over design, kHz frequency alternating currents (KFAC) and pulsed currents (PC) with narrow (200 µs) or wide (500 µs) phase durations were randomly applied on knee extensor muscles of healthy participants with a minimum of seven days between sessions. The NMES-evoked torque, NMES-efficiency, and discomfort (visual 0−10 cm analogue scale) were measured for…