Irinotecan is an effective treatment for metastatic colorectal cancer. However, its use may be associated with troublesome adverse effects such as delayed diarrhoea, acute cholinergic syndrome and ...neutropenic infection. The manufacturer decided to release irinotecan for compassionate use in The Netherlands prior to its regulatory approval (June 1998) and first introduction for second-line treatment of metastatic colorectal cancer. In view of the drug's adverse effect profile this was done in a carefully controlled manner.
Irinotecan was made available to patients with colorectal cancer with elaborate precautions. Treating physicians requesting irinotecan for compassionate use received a protocol, providing recommendations for the proper use and the prevention/management of potentially troublesome adverse events. Limited demographic, toxicity and efficacy data were collected.
Between June 1997 and September 1998, 112 patients were registered for this programme, 103 of whom actually received irinotecan. The percentage of patients experiencing grade 3-4 adverse effects was relatively low: delayed diarrhoea in 17%, nausea and vomiting 17%, acute cholinergic syndrome 6%, febrile neutropenia 4% and neutropenic infection 2%. Five partial tumour responses and a high proportion of patients with 'no change' were noted.
The carefully controlled release of irinotecan for compassionate use with a very detailed protocol for guidance and advice on safety precautions seems to have contributed to the relatively safe use of the drug outside the setting of a formal clinical trial.
The β + /EC decay of 182,184 Tl to excited states in the daughter nuclei 182,184 Hg has been investigated at the CERN on-line isotope mass separator facility. In both Tl nuclei two β-decaying states ...were observed. In the case of 184Tl, narrow-band laser spectroscopy could be used to disentangle the decay of both isomers. In 182Hg a precise energy of 335 (1) keV for the 0 2 + state was measured together with its feeding from a tentatively proposed 2 3 + state at 973 keV. Large conversion coefficients for the 2 2 + → 2 1 + transition in 182,184 Hg were measured to be 7.2 (13) and 14.2 (36), respectively, evidencing a strong E0 component.
As physician-essayist Lewis Thomas has urged, ignorance-based courses and curricula are urgently needed in medical education to prepare future generations of scientific physicians and ...physician-scientists for the uncertain, rapidly changing world ahead. This article reviews the evolving concept of ignorance in general and specifically in medicine and its relationship to knowledge. Issues about goals, content, and assessment of such ignorance-based courses are discussed along with the experience of the University of Arizona's National Institutes of Health-sponsored Summer Institute on Medical Ignorance for medical student researchers and disadvantaged high school students. Summer Institute on Medical Ignorance activities can be readily replicated or adopted in their entirety or partially in both live and Internet-based formats. These will serve to introduce medical ignoramics and questioning as a way to balance the information-overloaded medical curriculum.
This paper presents a new approach in vector quantization that is designed for clustering or source coding. It incorporates both the capability of fast convergence from a monotonically descending ...algorithm and provides a globally optimal solution by a random optimization technique. Thus, it benefits from properties of deterministic and stochastic search. Comprehensive experiments demonstrate that the new algorithm actually assimilated the advantages of the both components. It may be therefore regarded as an accelerated global optimization method whose convergence is theoretically proved. According to the complexity of the quantization problem, the convergence rate is shown (numerically) to approach that of a coordinate descent algorithm, which is an iterative updating of a single codevector at a time (generalized Lloyd algorithm GLA, i.e., K-means). The new method is investigated and compared with GLA and a globally operating stochastic relaxation technique. The comparison was made with respect to quality, reliability, and efficiency and applied to four categories of data: an easy to grasp example, patterns derived from the EEG, Gauss-Markov, and image sources.
Neuronal activity during information processing is represented by oscillations within local or widespread neuronal networks. These oscillations may be recorded by the EEG (electroencephalogram). The ...oscillatory interaction between neuronal ensembles may be at one single frequency or at different frequencies due to non-linear coupling. The investigation of momentary coherence and phase enables the examination of synchronized oscillatory network activity during fast-changing cognitive processes. On this basis information transfer from occipital areas towards frontal areas could be described during processing of visual presented words. Non-linear phase coupling between oscillations with different frequencies during memory processing was detected by means of cross-bicoherence.
Gallium nitride layers grown by metal organic vapour phase epitaxy on sapphire were implanted with different ion species, i.e. silicon, sulfur, and magnesium, and thermally annealed at 1150 °C under ...nitrogen atmosphere. The impact of this annealing procedure on the resulting deep levels was analyzed by transient and admittance spectroscopy. Several electron traps with thermal activation energies between 200 and 900 meV as well as very deep states at photon energies ranging from 1.8 to 2.5 eV were induced by the implantation process independent of the ion species. After annealing, in general the deep level spectrum shows only minor changes, but an enhancement of the shallower electron traps and a new electron trap for the Si‐implanted layers can be observed. These results are explained by a re‐arrangement of the induced defects and supported by photoluminescence experiments. Finally, the ineffectiveness of this annealing procedure which is often used by the community to reduce the implantation damage is demonstrated.
Thirty-four adult patients with portomesenteric venous occlusion (PVO) were reviewed. In 11 with hepatic cirrhosis, PVO was usually heralded by worsening ascites often with varix hemorrhage; ...mortality was high. Four with isolated portal block had varix hemorrhage without ascites. All of these patients survived despite recurrent hematemesis when portal decompression was not feasible in two patients. Eight others (5 agnogenic and 3 with hypercoagulability), experienced sudden abdominal pain with a clot typically propagated into mesenteric tributaries with ileojejunal infarction; survival was related to the promptness of operation and the extent of bowel ischemia. Of five patients with intraabdominal sepsis and pylephlebitis, only one survived. In the final six patients, PVO occurred with intraabdominal carcinoma. Five had progressive ascites, cachexia, and an early death. Imaging techniques included plain and contrast roentgenograms, ultrasonography, and for definitive diagnosis direct portography (operative or splenoportogram), indirect portography (splanchnic arteriovenogram), and computed tomography. Thirteen of 34 patients had ascites, and in nine of 11 patients examined, protein concentration of ascitic fluid was extremely low (less than 0.6 g/dl). Clinical presentation of PVO varies, depending on acuteness and extent of visceral venous blockade, severity of portal hypertension, auxiliary venous collateralization, and regional lymph flow. Inciting factors include endothelial damage and blood hypercoagulability from trauma, infection, stagnant circulation, blood dyscrasia, and malignancy. Improved imaging now allows early diagnosis.
Diagnosing congenital lymphatic dysplasia and counseling the parents of babies with possible genetic conditions represents a difficult task. This article attempts to provide a guide to establishing ...genetic tools and a reference library for use in the diagnostic work-up of congenital lymphatic diseases. The tools that are outlined herein are not meant to replace genetic counseling; their role is merely to facilitate the interaction between lymphologist and geneticist. These tools are a way of identifying lymphatic dysplasias at a very early stage.
The even-even nucleus 142Xe lies north-east of the doubly magic 132Sn on the neutron-rich side of the nuclear chart. In order to gain further information on the octupole collectivity and the ...evolution of quadrupole collectivity in this region, a "safe" Coulomb excitation experiment was carried out at the new HIE-ISOLDE facility (CERN) at the end of 2016. As the gamma-ray detector the Miniball spectrometer was used. Beam and target nuclei were detected using C-REX, i.e. an array of segmented Si detectors, covering forward as well as backward angles in the laboratory frame.
PDF
