Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Experimental and model determination of human intervertebral disc osmoviscoelasticity

Finite element (FE) models have become an important tool to study load distribution in the healthy and degenerated disc. However, model predictions require accurate constitutive laws and material properties. As the mechanical properties of the intervertebral disc are regulated by its biochemical composition and fiber‐reinforced structure, the relationship between the constitutive behavior of the tissue and its composition requires careful consideration. While numerous studies have investigated the annulus fibrosus compressive and tensile properties, specific conditions required to determine model parameters for the osmoviscoelastic model are unavailable. Therefore, the objectives of this study were (1) to complement the existing material testing in the literature with confined compression and tensile tests on human annulus fibrosus and (2) to use these data, together with existing nucleus pulposus compression data to tune a composition‐based, osmoviscoelastic material constitutive law. The osmoviscoelastic material constitutive law and the experimental data were used to describe the fiber and nonfiber properties of the human disc. The compressive material properties of normal disc tissue were G_m = 1.23 MPa, M = 1.57, and α = 1.964 × 10^?16 m⁴/Ns; the tensile fiber material parameters were E₀ = 77.0 MPa; E_ε = 500 MPa, and η = 1.8 × 10³ MPa^?s. The goodness of fit ranged from 0.88 to 0.96 for the four experimental conditions evaluated. The constitutive law emphasized the interdependency of the strong swelling ability of the tissue and the viscoelastic nature of the collagen fibers. This is especially important for numerical models to further study the load sharing behavior with regard to disc degeneration and regeneration. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1141–1146, 2008     

Are adipose‐derived stem cells cultivated in human platelet lysate suitable for heart valve tissue engineering?

Tissue‐engineered heart valves represent a promising strategy for the growing need for valve replacements in cardiovascular medicine. Recent studies have shown that adipose‐derived stem cells (ADSC) are a viable cell source, as they are readily available in both the young and the elderly, show diverse differentiation potential and adapt their extracellular matrix (ECM) to a varying mechanical load. In vitro culture medium is usually enriched with fetal calf serum (FCS). However, a promising substitute has recently been found in human platelet lysate (HPL), which is superior in terms of proliferation speed and allogenicity. This study sought to elucidate the suitability of ADSC and HPL for heart valve tissue engineering (TE). ADSC harvested from five healthy individuals were cultured in both FCS and HPL. The cells were observed for differentiation potential, proliferation speed and immunophenotype, using immunohistochemistry and FACS analysis. Neotissue was assessed for ECM composition, human collagen I (hColl1) formation, histomorphology and mechanical stiffness under uniaxial tensile stress. Neotissue cultured in HPL was found to be significantly inferior in mechanical rigidity; it showed a three‐fold higher proliferation rate and a more dense ECM, but also a more heterogeneous hColl1 distribution. ECM analysis showed significantly higher amounts of DNA and glycosaminoglycans (GAG) in HPL‐cultured tissue. No significant differences were observed for differentiation potential and immunophenotype, apart from a lower CD166 expression in HPL. The mechanical inferiority of neotissue cultured in HPL represents a limitation to the use of HPL‐enriched media for heart valve TE with ADSC. This result concurs with data published about HPL and myofibroblasts derived from the venous wall. Similarly, the mechanical inferiority is not rooted in a difference in ECM composition, but rather in hColl1 architecture. Stem cell properties, as documented in the literature, are retained with HPL. A possible connection between the mechanical inferiority and the observed decrease in CD166 needs further investigation. Copyright © 2016 John Wiley & Sons, Ltd.     

The effects of physical exercise on plasma levels of relaxin,NTproANP, and NTproBNP in patients with ischemic heart disease

The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO < 1.96 W) had higher NTproANP and NTproB-NP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease.     

Late cardiotoxicity after treatment for Hodgkin lymphoma

We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared with the general population (standardized incidence ratios [SIRs] = 3.6 and 4.9, respectively), resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10 000 patients/year. SIRs of all CVDs combined remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (hazard ratios [HRs] were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared with the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy.     

The etiology of pressure ulcers: skin deep or muscle bound?

Pressure ulcers are areas of soft tissue breakdown that result from sustained mechanical loading of the skin and underlying tissues; they can affect the quality of life of many individuals. Despite considerable efforts to prevent pressure ulcers, data on prevalence are unacceptably high. This can at least partly be attributed to limited knowledge of the etiology of the clinical condition and the fact that identification and prevention of pressure ulcers mainly focus on skin tissue, even though the underlying muscle tissue may be more susceptible to mechanical loading. The present article proposes a new, hierarchical research approach to obtain improved insights into the basic pathways whereby mechanical loading leads to soft tissue breakdown. This approach investigates the relationships between (1) global mechanical loading at skin level, (2) the resulting local internal mechanical conditions within the soft tissue layers extending from skin to muscle tissue, and (3) the pathophysiologic response to loading. The latter response should be assessed from the various functional tissue units involved in soft-tissue breakdown-the cells, the interstitial space, and blood and lymph vessels. We predict that the proposed strategy will provide new fundamental knowledge about the etiology of pressure ulcers that can serve as a sound basis for effective clinical identification and prevention.     

Linkage of a familial platelet disorder with a propensity to develop myeloid malignancies to human chromosome 21q22.1-22.2

Linkage analysis was performed on a large pedigree with an autosomal dominant platelet disorder and a striking propensity in affected family members to develop hematologic malignancy, predominantly acute myelogenous leukemia. We report the linkage of the autosomal dominant platelet disorder to markers on chromosome 21q22. Four genetic markers completely cosegregate with the trait and yield maximum logarithm of difference scores ranging from 4.9 to 10.5 (theta = .001). Two flanking markers, D21S1265 and D21S167, define a critical region for the disease locus of 15.2 centimorgan. Further analysis of this locus may identify a gene product that affects platelet production and function and contributes to the molecular evolution of hematologic malignancy.     

Associations between both genetic and environmental biomarkers and lung cancer: evidence of a greater risk of lung cancer in women smokers

This molecular epidemiologic case-control study of lung cancer incorporated three complementary biomarkers: the glutathione S- transferase M1 (GSTM1) null genotype, a potential marker of susceptibility, and polycyclic aromatic hydrocarbon-DNA adducts (PAH- DNA) and sister chromatid exchanges (SCE), both indicators of environmentally induced genetic damage. Associations between biomarkers and lung cancer were investigated, as were possible gene-environment interactions between the GSTM1 null genotype and tobacco smoke exposure. Subjects included 136 primary non-small cell lung cancer surgical patients and 115 controls at the Columbia Presbyterian Medical Center. Questionnaire and Tumor Registry data, pre-treatment blood samples and biomarker measurements on blood were obtained. Overall, GSTM1 null genotype was significantly associated with lung cancer [odds ratio (OR) = 2.04, 95% confidence interval (CI) = 1.13-3.68]. ORs for GSTM1 and lung cancer were significant in females (2.50, 1.09-5.72) and smokers (2.25, 1.11-4.54) and not significant in males (1.4, 0.58-3.38) and non-smokers (0.88, 0.18-4.33). However, ORs for males versus females and smokers versus non-smokers did not differ significantly. The OR for GSTM1 and lung cancer in female smokers was 3.03 (1.09- 8.40), compared with 1.42 (0.53-4.06) in male smokers. In contrast to PAH-DNA adducts in leukocytes, SCE did not differ between cases and controls. Neither biomarker differed significantly between the two GSTM1 genotypes. The combined effect of elevated PAH-DNA adducts and GSTM1 genotype on case-control status (16.19, 1.2-115) appeared multiplicative. Results suggest that the effect of the GSTM1 null genotype is greatest in female smokers, which is consistent with other evidence that indicates that women are at higher risk of lung cancer than males, given equal smoking. Persons with both the GSTM1 deletion and elevated PAH-DNA adducts may represent a sensitive subpopulation with respect to carcinogens in tobacco smoke and other environmental media.      

红景天属植物中红景天甙的高效液相色谱分析

采用ODS柱,以甲醇—水(2:8)为流动相,在276nm检测波长下,测定了大花红景天、互生红景天、喜马红景天、云南红景天和四裂红景天5种生药以及大花红景天提取物10个样品中的红景天甙的含量。     

Deposition of autofluorescent eosinophil granules in pathologic bone marrow biopsies

Eosinophil granules are intensely autofluorescent when excited by green light. To determine if eosinophils degranulate in the bone marrows of patients with a variety of diseases, we used green light epifluorescence microscopy to examine deparaffinized and dezenkerized sections of 49 bone marrow core biopsies. In 14 of the biopsies, there was striking extracellular deposition of intensely autofluorescent eosinophil granules in addition to numerous intact eosinophils. Among the 14 specimens with extracellular autofluorescence were seven cases of leukemia, four cases of non-Hodgkin's lymphoma, two cases of myelofibrosis, and one case of pancytopenia with eosinophilia. In the remaining 35 specimens, only intact eosinophils were identifiable. There was no extracellular autofluorescence in three normal marrows, four marrows from AIDS patients, or three biopsies from patients with idiopathic thrombocytopenic purpura (ITP). We conclude that green light epifluorescence microscopy identifies extracellular deposits of eosinophil granules in bone marrow biopsies of some neoplastic disorders and in diseases associated with reticulin fibrosis.