Diagnostic accuracy and safety of CT-guided percutaneous needle aspiration biopsy of the lung: comparison of small and large pulmonary nodules

OBJECTIVES: Uncontrolled data often have to be used in clinical decision marking and in the planning of clinical trials. When such data are used as a basis for comparing different treatment strategies, they tend to generate sources of bias such as inconsistent patient selection, misrepresentation, and measurement errors. A rational usage of uncontrolled data requires identification and handling of different systematic errors when comparing different treatment strategies. Therefore we sought to define a systematic error that deserves more attention in the clinical literature. METHODS: Using hypothetical examples, we illustrate the bias introduced by variations in "lead time," proportions of so-called prevalent/incident cases, and lengths of follow-up between reference and treatment groups. RESULTS: We found these three situations conceptually identical. Bias is introduced because different parts of a nonconstant hazard curve over time are observed. CONCLUSIONS: The systematic error described is potentially important in uncontrolled data provided the hazard rate over time is nonconstant. Thus the seemingly worse outcome after external beam radiation therapy as compared to the outcomes of deferred treatment of radical prostatectomy in compiled patient series of localized prostate cancer may in some part be explained by bias due to observation of different parts of a nonconstant hazard curve over time.     

Modulation by presynaptic beta-adrenoceptors of noradrenaline release from sympathetic nerves in human dental pulp

BACKGROUND: Severe and therapy-resistant pruritus is the most prominent feature of macular (MA) and lichen (LA) amyloidosis that leads to further amyloid deposition by recurrent frictional trauma to the epidermis. Of the various therapeutic modalities with variable success, the most encouraging and beneficial effect has been observed with topical dimethyl sulfoxide (DMSO) therapy. In a previous study, we achieved marked clinical improvement in nine of 10 patients in a daily treatment regimen over 6-20 weeks, but relapses occurred in the post-treatment follow-up period. The aims of this study are to investigate whether the patients would benefit from intermittent therapy and to determine the optimal application interval of DMSO to maintain the relief of symptoms. METHODS: Thirteen patients with histopathologically verified cutaneous amyloidosis (five MA, two LA and six biphasic) were enrolled in the study. They were treated once daily with a 50 or 100% DMSO solution until pruritus disappeared. Then, DMSO was applied at increasing intervals until the widest effective application interval for maintenance of relief was reached. Patients were regularly followed-up by a scoring system for pruritus, papules, and pigmentation, control biopsies, photographs, blood biochemistry, and side-effects. RESULTS: The mean time required for the disappearance of pruritus was 4.1 weeks. Remarkable flattening of the papules was achieved after an average therapy period of 9 weeks. After a total therapy period of 6.5 months, a nearly 50% remission in pigmentation and >70% flattening of papules were achieved. The widest effective DMSO application interval was 8.6 days. The side-effects of therapy were contact urticaria, desquamation, burning sensation, and garlic-like breath odor, which were more prominent with the higher concentration of DMSO. In interval therapy, side-effects were tolerated more easily than in daily therapy. No reduction of amyloid deposits was revealed in control biopsies. CONCLUSIONS: Locally applied DMSO can break the vicious "pruritus-amyloid deposition-pruritus" cycle in patients with MA and LA. In addition to its daily use, interval therapy seems to maintain this effect and enables patients to tolerate side-effects more easily.     

Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity

This article reviews the evidence that the nodular form of lymphocyte predominance Hodgkin's disease ("nodular paragranuloma") should be recognised as a distinct clinico-pathological entity. The disease is characterised histologically by very large primary lymphoid follicles, containing polytypic small B lymphocytes and extensive meshworks of follicular dendritic cells. The "L and H" or "popcorn" cells scattered within the nodules show clear differences from classical Reed-Sternberg cells, both in their cytological appearance and in their marker profile, being frequently negative for CD15 and for the EBV genome, but often positive for B cell antigens, CD45 (leucocyte common antigen), CDw75 (LN1), epithelial membrane antigen (EMA) and J chain. These findings suggest that L and H cells may be Ig-synthesising monoclonal B cells. Nodular lymphocyte predominance Hodgkin's disease pursues a much more indolent courses that classical Hodgkin's disease, and long term survival is common. It has other distinctive clinical features, e.g. a unimodal age distribution, a predilection to involve single lymph nodes, and a very low incidence of thymic involvement. There is a tendency for diffuse large cell non-Hodgkin's lymphoma, usually of B cell type, to develop during the course of the disease. This type of Hodgkin's disease thus has many features that distinguish it from the nodular sclerosis and mixed cellularity varieties, and it is hoped that future studies will gather more information on its clinical behavior and on the nature of the putative neoplastic cells, as well as exploring different protocols for its treatment.     

固定蜂窝系统话音质量

对话音质量的评断往往非常主观，而“用户平均评价记分（ＭＯＳ）”方法则能提供一个较为客观的评价，休斯网络系统（ＨＮＳ）的ＧＭＨ２０００固定蜂窝系统获得了极高的ＭＯＳ，这意味着该系统提供的话音品质很高。本文介绍了影响固定蜂窝系统话音质量的一些关键因素，对模拟和数字数字蜂窝系统的ＭＯＳ评价作了比较，最后简述了ＧＭＨ２０００高话音品质的原因。     

Modeling, chemistry, and biology of the benzolactam analogues of indolactam V (ILV). 2. Identification of the binding site of the benzolactams in the CRD2 activator-binding domain of PKCdelta and discovery of an ILV analogue of improved isozyme selectivity

Protein kinase C (PKC) is a complex enzyme system comprised of at least 11 isozymes that serves to mediate numerous extracellular signals which generate lipid second messengers. The discovery of isozyme-selective activators and inhibitors (modulators) of PKC is crucial to ascertaining the role of the individual isozymes in physiological and pathophysiological processes and to manipulating their function. The discovery of such small molecule modulators of PKC is at present a largely unmet pharmacological need. Herein we detail our modeling studies which reveal how the natural product indolactam V (ILV) and its 8-membered ring analogue, the benzolactam 15, bind to the CRD2 activator domain of PKC. These modeling studies reveal that not all PKC ligands possess a common pharmacophore, and further suggest an important role of specific hydrophobic contacts in the PKC-ligand interaction. The modeling studies find strong experimental support from mutagenesis studies on PKC alpha that reveal the crucial role played by the residues proline 11, leucine 20, leucine 24, and glycine 27. Next, we describe the synthesis of two 8-substituted benzolactams starting from L-phenylalanine and characterize their isozyme selectivity; one of the two benzolactams exhibits improved isozyme selectivity relative to the n-octyl-ILV. Lastly, we report inhibition of cellular proliferation of two different breast carcinoma cell lines by the benzolactam 5 and show that the compound preferentially down-regulates PKCbeta in both cell lines.     

Perchlorate uptake by synthetic layered double hydroxides and organo-clay minerals

The perchlorate uptake of hydrotalcite- and hydrocalumite-type layered double hydroxides (LDHs), and surfactant modified clay minerals were compared. Perchlorate uptake by both hydrotalcite- and hydrocalumite-type LDHs was in the range of 0.011 to 0.197 meq/g from a 2 mM perchlorate solution. The nitrate form of Mg:Al LDH had the highest uptake of 0.197 ± 0.033 meq/g, and the carbonate form of LDH the lowest uptake of 0.011 ± 0.003 meq/g. Octadecyltrimethylammonium (ODTMA), Dodecyltrimethylammonium (DoDTMA), and hexadecyltrimethylammonium (HDTMA) clay minerals removed perchlorate in the range of 0.025 to 0.348 meq/g from a 2 mM perchlorate solution. Synthetic HDTMA (5.0 CEC) Na-1-mica exhibited the highest adsorption of perchlorate with 0.348 ± 0.011 meq/g, while DoDTMA montmorillonite had the lowest adsorption with 0.025 ± 0.009 meq/g. Tested under the same conditions, a surfactant modified carbon showed an uptake of 0.303 ± 0.005 meq/g and this carbon is currently being used for filtration of drinking water.Hydrophobic organo-clay minerals with larger interlayer distance resulted in higher perchlorate uptake by exchange/adsorption on the residual charge of the cationic surfactants. The uptake by LDH was by anion exchange on the surfaces and, for the nitrate form of hydrotalcite, also from the interlayer spaces. The mechanisms of uptake were confirmed by X-ray diffraction (XRD) and scanning electron microscopy. This study indicated that cationic surfactant containing organo-clay minerals may be useful materials for the removal of perchlorate from water and could serve as alternatives to surfactant modified-activated carbons.     

Transient Growth Bands in Silicon Nitride Cooled in Rare-Earth-Based Glass

Silicon nitride (Si₃N₄) particles embedded in various R-SiAl-O-N glasses (R = La, Nd, Gd, Yb) have been systematically studied by high-resolution transmission electron microscopy and by analytical electron microscopy. The particles typically show an internal growth band, which is attributed to the enhanced growth of the particles in the supersaturated silicate liquid during cooling and reheating. The electron energy-loss spectroscopy and energy-dispersive X-ray spectroscopy analysis reveal that the growth band typically contains lanthanide elements. This trapping, especially of the lighter lanthanide elements, within the lattice of the β-SiAlON is obviously beyond the general expectation that the lighter lanthanide ions hardly form solid solutions with either α- or β-Si₃N₄. This ultimately provides some clues regarding the mobility of the lanthanide ions in the liquids and also revives interest in the general question of the possible effect of a cooling stage on the structures and compositions of the intergranular film and of the grain/glass interface in the Si₃N₄-based polycrystalline ceramics.     

Fracture and Fatigue Behavior at Ambient and Elevated Temperatures of Alumina Bonded with Copper/Niobium/Copper Interlayers

Interfacial fracture toughness and cyclic fatigue-crack growth properties of joints made from 99.5% pure alumina partially transient liquid-phase bonded using copper/niobium/copper interlayers have been investigated at both room and elevated temperatures, and assessed in terms of interfacial chemistry and microstructure. The mean interfacial fracture toughness, G _c, was found to decrease from 39 to 21 J/m² as temperature was raised from 25° to 1000°C, with failure primarily at the alumina/niobium interfaces. At room temperature, cyclic fatigue-crack propagation occurred both at the niobium/alumina interface and in the alumina adjacent to the interface, with the fatigue threshold, Δ G _TH, ranging from 20 to 30 J/m²; the higher threshold values in that range resulted from a predominantly near-interfacial (alumina) crack path. During both fracture and fatigue failure, residual copper at the interface deformed and remained adhered to both sides of the fracture surface, acting as a ductile second phase, while separation of the niobium/alumina interface appeared relatively brittle in both cases. The observed fracture and fatigue behavior is considered in terms of the respective roles of the presence of ductile copper regions at the interface which provide toughening, extrinsic toughening due to grain bridging during crack propagation in the alumina, and the relative crack propagation resistance of each crack path, including the effects of segregation at the interfaces found by Auger spectroscopy.