灾难的时代错误:灾害医学的过去、现在和将来(一)

灾难,特别是地震、火山、洪水以及与战争有关的事件如饥饿和流行性传染病,是人类有记录的经历的一部分。从意大利庞贝的火山爆发,到约翰斯顿的洪水、第二次世界大战和黑色瘟疫,到西班牙流感,都发生了灾难,这不会被传说和历史书籍长期忘却。不过,在20世纪中叶以前,那些灾难的发生相对较少,且相距时间较长。从20世纪中叶以来,灾难的本质发生了变化。从恐怖分子使用“新技术”,到与气候有关的导致亿万美元经济损失的事件,表明这个世界正在发生变化。仅仅在最近的50~60年间,造成多种多样的伤亡事件,其危险性和频率的增加引人注目,并且注定要在接…     

Mitozolomide activity on human cancer cells in vitro

The growth inhibitory effects, the reduction of [3H]-TdR incorporation and the perturbation of the cell cycle induced by the new agent mitozolomide on the M14 human melanoma cell line and on the SW626 human ovarian cancer cell line were compared to those produced by BCNU. Flow cytometry showed an interesting difference: at the high concentration mitozolomide induced an accumulation of cells in S middle and S late-G2-M phase of the cell cycle whereas BCNU caused only a block in S late-G2-M. Further studies were aimed at investigating the susceptibility of freshly isolated human ovarian cancer cells to pharmacologically reasonable mitozolomide concentrations. Only in one out of 16 primary cultures of human ovarian cancers was mitozolomide able to induce cell cycle perturbation, suggesting that ovarian carcinoma cells may not be sensitive to this drug.     

Conditional estimation of sensitivity and specificity from a phase 2 biomarker study allowing early termination for futility

Development of a disease screening biomarker involves several phases. In phase 2 its sensitivity and specificity is compared with established thresholds for minimally acceptable performance. Since we anticipate that most candidate markers will not prove to be useful and availability of specimens and funding is limited, early termination of a study is appropriate, if accumulating data indicate that the marker is inadequate. Yet, for markers that complete phase 2, we seek estimates of sensitivity and specificity to proceed with the design of subsequent phase 3 studies. We suggest early stopping criteria and estimation procedures that adjust for bias caused by the early termination option. An important aspect of our approach is to focus on properties of estimates conditional on reaching full study enrollment. We propose the conditional‐UMVUE and contrast it with other estimates, including naïve estimators, the well‐studied unconditional‐UMVUE and the mean and median Whitehead‐adjusted estimators. The conditional‐UMVUE appears to be a very good choice. Copyright © 2008 John Wiley & Sons, Ltd.     

The detection of internal mammary lymph nodal chain metastases in breast cancer using radiolabelled colloids

The authors report their studies of 39 lymphoscintigraphies performed on patients with breast cancer. They point out that interpretation of scintigraphic imaging must take into account the morphologic variations of the lymph nodes of the internal mammary chains (i.e. single central chain, single central lymph node) and the morphological difference in the symmetry of lymph nodes considered non-pathologic to avoid false positives. The authors retain that lack of visualization of a chain, conspicuous increase in size of a lymph node, asymmetry of pathologic development, or reduced uptake by one or more lymph nodes of the internal mammary chains must be interpreted as a sign of metastatic spread. The authors recommend lymphoscintigraphy as an effective technique in the screening of breast cancer patients for staging, follow-up, restaging, and planning of radiotherapy.     

Perfusion of rat colon with sennosides, rhein and rheinanthrone. Concentration-related histamine release.

Rat colon perfused intraluminally in vitro and in vivo released histamine into the perfusates. Histamine release was increased by rhein 0.1-10 micrograms/ml and much more by rheinanthrone 0.1-10 micrograms/ml but not by sennosides A or B 1-10 micrograms/ml. The effect of rhein and rheinanthrone was reduced by tritoqualine 20 mg/kg. This raises the possibility that laxation by senna and its derivatives involves histamine formation.     

Geographic patterns of urban trauma according to mechanism and severity of injury

The purpose of this study was to investigate the distribution of various mechanisms of injury and the relative severity of such injury cases throughout the different geographic zones of a large urban area using a computerized emergency medical services (EMS) dispatch/patient record database. The study city (population, 2 million residents) was divided into 156 geographic grids (each 4.5 by 3 miles) and the incidence and relative severity of various injury mechanisms were determined for each zone. Results: In one year (1988), there were more than 115,000 separate EMS incidents involving more than 150,000 patients, 26,000 of whom were transported for injuries incurred in 10,064 motor vehicle accidents, 4,587 falls, 4,015 lacerations/stabwounds, 1,796 beatings, 1,270 gunshots, and 952 auto-pedestrian accidents. Analysis of the 156 zones showed a disproportionate number of EMS responses in the city center with two centralmost grids accounting for about 25% of all responses. Call volume then progressively diminished toward the periphery of the city. However, with some very minor exceptions, the relative incidence and severity of the various injury mechanisms remained proportionally uniform within each zone, regardless of geographic location. Therefore, contrary to popular notoriety, the incidence and associated severity of any given injury type generally was not necessarily predicted by any particular neighborhood predilection for it, but rather by the overall demand for EMS in that zone of the city.     

Differences in airway remodeling between subjects with severe and moderate asthma

BACKGROUND: Airway remodeling in asthma comprises a range of structural changes. Several studies have suggested an association between these changes and disease severity. The relationship between the extent of remodeling and lung function is not well defined. OBJECTIVE: We sought to contrast the structural changes in the airways of well-defined groups of subjects with severe and moderate asthma and to correlate the extent of remodeling with disease severity. METHODS: Endobronchial biopsy specimens were obtained from 15 subjects with severe and 13 subjects with moderate asthma. Epithelial integrity, cell-layer areas, subepithelial fibrosis, and the distance between epithelial and airway smooth muscle (ASM) layers were measured by means of image analysis. Collagen was identified by using Van Giesen stain, and ASM was defined by using smooth muscle alpha-actin immunostaining. Specific immunostains were performed for the evaluation of RANTES, IL-8, and eotaxin expression as markers of ASM phenotype. RESULTS: ASM area was greater in subjects with severe (0.24+/- 0.03 mm(2)) than in subjects with moderate (0.05+/- 0.01 mm(2)) asthma (P<.001). The distance between the epithelial and ASM layers was less in the severe group (0.12+/- 0.01 mm) than in the moderate group (0.24+/- 0.02, P<.001). A trend toward greater subepithelial fibrosis in subjects with severe asthma did not reach statistical significance. IL-8 and eotaxin expression, but not RANTES expression, were increased in the ASM of subjects with severe asthma compared with in subjects with moderate asthma. CONCLUSION: Smooth muscle alteration is the key structural change that distinguishes severe from moderate asthma, and phenotypic change in ASM might contribute to the difficulty in obtaining adequate control in some subjects with severe asthma.