Histologic analysis of ruptured quadriceps tendons

Quadriceps tendon ruptures are uncommon injuries. Degenerative changes in the tendon are felt to be an important precondition for rupture. We retrospectively reviewed 45 quadriceps tendon ruptures in 42 patients. Quadriceps tendon ruptures occurred most often in the sixth and seventh decade of life. Men were affected six times as often as women. A tissue sample from the rupture-zone was obtained in 22 cases and histologic analysis was performed. Degenerative changes were present in only 14 (64%) of the 22 samples. We observed an increasing ratio of degenerative to nondegenerative tendons with increasing patient age. Our data suggests that quadriceps tendon rupture, especially in younger patients, can occur in the absence of pathologic tendon degeneration.     

Histologic analysis of radiofrequency energy chondroplasty

Two types of radiofrequency energy are currently used for chondroplasty: thermal and ablative. The primary mode of operation for monopolar radiofrequency energy is thermal, whereas the primary mode for bipolar radiofrequency energy is ablation. The safety of radiofrequency energy in articular cartilage is investigated because these treatment modalities can result in injury of target and surrounding tissues. Histologic analysis is used to assess this degree of damages and the efficacy of these techniques, but the accuracy and relevance of the results are affected by the design and duration of the analysis. A review of recent studies using different methods of histologic analysis of articular cartilage subject to radiofrequency energy techniques is presented.     

The efficacy of DNA mixture to mixture matching

Standard practice in forensic science is to compare a person of interest’s (POI) reference DNA profile with an evidence DNA profile and calculate a likelihood ratio that considers propositions including and excluding the POI as a DNA donor. A method has recently been published that provides the ability to compare two evidence profiles (of any number of contributors and of any level of resolution) comparing propositions that consider the profiles either have a common contributor, or do not have any common contributors. Using this method, forensic analysts can provide intelligence to law enforcement by linking crime scenes when no suspects may be available. The method could also be used as a quality assurance measure to identify potential sample to sample contamination. In this work we analyse a number of constructed mixtures, ranging from two to five contributors, and with known numbers of common contributors, in order to investigate the performance of using likelihood ratios for mixture to mixture comparisons. Our findings demonstrate the ability to identify common donors in DNA mixtures with the power of discrimination depending largely on the least informative mixture of the pair being considered. The ability to match mixtures to mixtures may provide intelligence information to investigators by identifying possible links between cases which otherwise may not have been considered connected.     

脑组织对DNA双链断裂的反应

DNA双链断裂是电离辐射引起的最严重DNA损伤形式,脑组织对DNA损伤的反应与其发展程度密切相关,脑组织中增殖细胞主要是通过同源重组进行修复,而分化细胞则通过非同源末端联接修复。DNA双链断裂信号通路相关因子的缺陷会导致一系列的有神经病理表现的人类遗传病。重点讨论电离辐射触发脑细胞DNA双链断裂后,信号转导相关因子和与相关因子导致的神经系统人类遗传疾病。     

Forensic molecular biomarkers for mixture analysis

The deconvolution of DNA mixtures has gathered the attention of forensic DNA scientists for over two decades. To enhance mixture deconvolution capabilities, a new generation of sensitive DNA-typing approaches has been recently proposed. In this review, we describe novel, forensically relevant multi-SNP loci (i.e., microhaplotypes or microhaps), compound markers (i.e., DIP-STRs, SNP-STRs and DIP-SNPs) and lineage markers (i.e., rapidly mutating Y chromosome STRs) that improve the deconvolution of two and more than two-person mixtures typed using conventional STR, binary and non-binary loci. We explore the features and applications of these emerging molecular biomarkers with respect to their ability to forensically detect same-or-opposite sex donors. Finally, we discuss the impact of initial massively parallel sequencing (MPS) investigations of STR, microhaplotype and SNP/indel assays for DNA mixture profiling.     

芦荟提取物对大鼠烫伤创面微血管形成的影响

目的探讨芦荟提取物对大鼠烫伤创面修复过程中微血管形成的影响。方法Wistar大鼠48只,随机分为8组,每组6只。每只背部造成4处直径3 cm深Ⅱ度烫伤创面,分别外涂质量分数分别为5%、10%、1%的芦荟粗多糖膏、芦荟凝胶膏、磺胺嘧啶银(SD-Ag)霜等渗盐水作空白对照,测量和计算烫伤后第10,14,18,21天创面面积,计算创面愈合率,并于烫伤前、伤后4 h、12 h、24 h、48 h和7 d、14 d、21 d分别取大鼠创面皮肤测定创面组织中血管内皮生长因子(VEGF)含量,采用Ⅷ因子免疫组织化学染色计算微血管密度(MVD)。结果5%芦荟粗多糖组和10%芦荟凝胶组(简称前者)与SD-Ag霜组和等渗盐水组(简称后者)相比,烫伤后14,18, 21 d,前者创面愈合率显著大于后者(P<0.05);烫伤后48 h、7 d、14 d和21 d,前者比后者创面VEGF含量显著增加(P<0.05);在烫伤后14 d和21 d,前者创面微血管密度显著大于后者(P< 0.05);而5%芦荟粗多糖组与10%芦荟凝胶组间、SD-Ag霜组与等渗盐水组间比较,差异无统计学意义。结论芦荟粗多糖和芦荟凝胶能通过增加烫伤创面组织VEGF的合成与释放,增加创面的微血管形成,促进创面愈合。     

Local tissue toxicity in response to extravascular extravasation of magnetic resonance contrast media

RATIONALE AND OBJECTIVES: The relative toxicities of the gadolinium chelates currently available in the United States were compared when extravasated in soft tissue. The increasing use of these contrast agents in higher volumes and at faster injection rates, often with a power injector, was a principal motivation for this research. METHODS: Gadopentetate dimeglumine (Magnevist), gadoteridol (ProHance), gadodiamide (Omniscan), and gadoversetamide (Optimark) were evaluated at standard concentration and compared with a control (physiologic saline) and the conventional ionic radiographic contrast medium meglumine diatrizoate (Renografin 60). Each mouse received a subcutaneous injection in the hindlimb of 0.3 mL of contrast or saline. There were 6 experimental groups, with 15 animals in each group. The individual performing the injection was blinded to the identity of the contrast agent used in each mouse. After 48 hours, the mice were killed and tissue samples obtained for histopathology. A veterinary pathologist, also blinded to the agent injected, graded the degree of damage seen on microscopic examination. RESULTS: Of the four MR contrast agents, gadopentetate dimeglumine caused the greatest tissue damage, and gadoteridol and gadodiamide-the two lowest osmolar agents-the least. The difference was statistically significant in terms of both inflammation (P = 0.0008 for gadoteridol, and P = 0.006 for gadodiamide) and necrosis (P = 0.0067 for gadoteridol, and P = 0.031 for gadodiamide), when these agents were compared with gadopentetate dimeglumine. In regard to the control experiments, for all three variables (necrosis, edema, and inflammation), there was no statistically significant difference between the results with gadoteridol or gadodiamide and those with saline. In terms of both edema and inflammation, the effect of gadopentetate dimeglumine, although less, could not be differentiated with any statistical significance from that of meglumine diatrizoate. Gadoversetamide, which has an osmolality between the ionic agent (gadopentetate dimeglumine) and the other two nonionic agents, caused a reaction that could not be differentiated from that seen with gadopentetate dimeglumine for both necrosis and edema. Only in the scoring of inflammation was the effect less using gadoversetamide compared to gadopentetate dimeglumine with any statistical significance (P = 0.021). CONCLUSIONS: The risk of tissue damage due to extravasation is not widely appreciated for the gadolinium chelates. Care should be exercised during contrast injection, to avoid inadvertent extravasation and its deleterious consequences, in particular with the two higher osmolar agents (gadopentetate dimeglumine and gadoversetamide).     

Histologic and electron microscopic analysis of experimentally transplanted CaM and MB16 tumors

Transplanted tumours (melanoma B16 and breast cancer) were analysed in different phases of development histologically and electronmicroscopically. The described specific ultrastructural changes of tumours cells in the course of neoplastic transformation have confirmed the supposition that the process of carcinogenesis is multiphasal and continuous.     

Real-time immunohistochemistry analysis of embedded tissue

We present a novel analysis of membrane–protein expression in tissue sections based on semi-automatic real-time measurement using LigandTracer^® technology. A commercial antiHER2 antibody developed for immunohistochemistry used in this setup was revealed to have sub-optimal interaction with tissue when analyzed as recommended for immunohistochemistry. We therefore think that real-time measurement of tissue, offering direct and quantitative membrane–protein interaction analysis, can lead to improved reproducibility and eliminate the subjective operator dependences that classical immunohistochemsitry suffers from.     

Computed tomography in the fatigue test analysis of an asphaltic mixture

This work applies the computerized tomography technique to the study of an asphaltic mixture. It was required to detect and follow the evolution of a crack, when this mixture was submitted to fatigue tests. The fatigue tests to produce stresses were done in a diametral compression equipment of repeated loading. The trajectory of a crack is influenced by original voids in the specimen; it may be noted that troughs exist in all tomographic images at the same positions and, as these could be due to voids, with a sufficient sequence of applied loads they would be transformed into a small crack that would increase in size, causing the collapse of the specimen. It was possible to detect and follow the evolution of a crack as the 900 blows were applied to the phantom. It was also noted that the crack begins to appear in the central region of the specimen and is propagated in the direction of the applied load.     

Predictive analysis of tumor response

To select the best treatment modality for individual patient with cancer, the oncologist is subjected to consider various factors and parameters predictive of the outcome of therapy. A critical review is presented relating to the prognostic factors in the local control and/or long term survival rate in various kinds of malignant tumors. As predictors of response in cancer patients, it is attributed not only to physical characteristics of ionizing radiation and technical factors, but also tumor- and host-related factors such as gene amplification, DNA pattern, nuclear shape factor, histological grade, growth rate, glucose metabolic state, NMR spectroscopy, tumor marker levels, shape and location of tumor, in vitro sensitivity assay of tumor, age, general immunologic competence and psychological state of the patient. Most of the studies done sofar, are focused on the involvement of only one or two factors for each tumor, but importance of each factor as a predictor of tumor response is not clearly highlighted. It is emphasized that multivariate analysis of all these factors including potential predictors should be performed for each malignant tumor and for each treatment modality.     

Automatic multi-modal MR tissue classification for the assessment of response to bevacizumab in patients with glioblastoma

Background

Current methods for evaluation of treatment response in glioblastoma are inaccurate, limited and time-consuming. This study aimed to develop a multi-modal MRI automatic classification method to improve accuracy and efficiency of treatment response assessment in patients with recurrent glioblastoma (GB).

Materials and methods

A modification of the k-Nearest-Neighbors (kNN) classification method was developed and applied to 59 longitudinal MR data sets of 13 patients with recurrent GB undergoing bevacizumab (anti-angiogenic) therapy. Changes in the enhancing tumor volume were assessed using the proposed method and compared with Macdonald's criteria and with manual volumetric measurements. The edema-like area was further subclassified into peri- and non-peri-tumoral edema, using both the kNN method and an unsupervised method, to monitor longitudinal changes.

Results

Automatic classification using the modified kNN method was applicable in all scans, even when the tumors were infiltrative with unclear borders. The enhancing tumor volume obtained using the automatic method was highly correlated with manual measurements (N = 33, r = 0.96, p < 0.0001), while standard radiographic assessment based on Macdonald's criteria matched manual delineation and automatic results in only 68% of cases. A graded pattern of tumor infiltration within the edema-like area was revealed by both automatic methods, showing high agreement. All classification results were confirmed by a senior neuro-radiologist and validated using MR spectroscopy.

Conclusion

This study emphasizes the important role of automatic tools based on a multi-modal view of the tissue in monitoring therapy response in patients with high grade gliomas specifically under anti-angiogenic therapy.     

Volume and Mass Doubling Time of Lung Adenocarcinoma according to WHO Histologic Classification

ObjectiveThis study aimed to evaluate the tumor doubling time of invasive lung adenocarcinoma according to the International Association of the Study for Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic classification.Materials and MethodsAmong the 2905 patients with surgically resected lung adenocarcinoma, we retrospectively included 172 patients (mean age, 65.6 ± 9.0 years) who had paired thin-section non-contrast chest computed tomography (CT) scans at least 84 days apart with the same CT parameters, along with 10 patients with squamous cell carcinoma (mean age, 70.9 ± 7.4 years) for comparison. Three-dimensional semiautomatic segmentation of nodules was performed to calculate the volume doubling time (VDT), mass doubling time (MDT), and specific growth rate (SGR) of volume and mass. Multivariate linear regression, one-way analysis of variance, and receiver operating characteristic curve analyses were performed.ResultsThe median VDT and MDT of lung cancers were as follows: acinar, 603.2 and 639.5 days; lepidic, 1140.6 and 970.1 days; solid/micropapillary, 232.7 and 221.8 days; papillary, 599.0 and 624.3 days; invasive mucinous, 440.7 and 438.2 days; and squamous cell carcinoma, 149.1 and 146.1 days, respectively. The adjusted SGR of volume and mass of the solid-/micropapillary-predominant subtypes were significantly shorter than those of the acinar-, lepidic-, and papillary-predominant subtypes. The histologic subtype was independently associated with tumor doubling time. A VDT of 465.2 days and an MDT of 437.5 days yielded areas under the curve of 0.791 and 0.795, respectively, for distinguishing solid-/micropapillary-predominant subtypes from other subtypes of lung adenocarcinoma.ConclusionThe tumor doubling time of invasive lung adenocarcinoma differed according to the IASCL/ATS/ERS histologic classification.     

Three-dimensional method for comparing in vivo interventional MR images of thermally ablated tissue with tissue response

PURPOSE: To investigate the ability of magnetic resonance (MR) to monitor radio-frequency (RF) ablation treatments by comparing MR images of thermal lesions to histologically assayed cellular damage. We developed a new methodology using three-dimensional registration for making spatial correlations. MATERIALS AND METHODS: A low-field, open MRI system was used to guide an ablation probe into rabbit thigh muscle and acquire MR volumes after ablation. After fixation, we sliced and photographed the tissue at 3-mm intervals, using a specially designed apparatus, to obtain a volume of tissue images. Histologic samples were digitized using a video microscopy system. For our three-dimensional registration method, we used the tissue images as the reference, and registered histology and MR images to them using two different computer alignment steps. First, the MR volume was aligned to the volume of tissue images by registering needle fiducials placed near the tissue of interest. Second, we registered the histology images with the tissue images using a two-dimensional warping technique that aligned internal features and the outside boundary of histology and tissue images. RESULTS: The MR and histology images were very well aligned, and registration accuracy, determined from displacement of needle fiducials, was 1.32 +/- 0.39 mm (mean +/- SD), which compared favorably to the MR voxel dimensions (0.70 mm in-plane and 3.0 mm thick). A preliminary comparison of MR and tissue response showed that the region inside the elliptical hyperintense rim in MR closely corresponds to the region of necrosis as established by histology, with a mean absolute distance between MR and histology boundaries of 1.17 mm, slightly smaller than the mean registration error. The MR region slightly overestimated the region of necrosis, with a mean signed distance between boundaries of 0.85 mm. CONCLUSION: Our results suggest that our methodology can be used to achieve three-dimensional registration of histology and in vivo MR images. In MR lesion images, the inner border of the hyperintense region corresponds to the border of irreversible cell damage. This is good evidence that during RF ablation treatments, iMRI lesion images can be used for real-time feedback.