Characterization of the interstitial lung diseases via density-based and texture-based analysis of computed tomography images of lung structure and function

RATIONALE AND OBJECTIVES: Efforts to establish a quantitative approach to the computed tomography (CT)-based character ization of the lung parenchyma in interstitial lung disease (including emphysema) has been sought. The accuracy of these tools must be site independent. Multi-detector row CT has remained the gold standard for imaging the lung, and it provides the ability to image both lung structure as well as lung function. MATERIAL AND METHODS: Imaging is via multi-detector row CT and protocols include careful control of lung volume during scanning. Characterization includes not only anatomic-based measures but also functional measures including regional parameters derived from measures of pulmonary blood flow and ventilation. Image processing includes the automated detection of the lungs, lobes, and airways. The airways provide the road map to the lung parenchyma. Software automatically detects the airways, the airway centerlines, and the branch points, and then automatically labels the airway tree segments with a standardized set of labels, allowing for intersubject as well intrasubject comparisons across time. By warping all lungs to a common atlas, the atlas provides the range of normality for the various parameters provided by CT imaging. RESULTS: Imaged density and textural changes mark underlying structural changes at the most peripheral regions of the lung. Additionally, texture-based alterations in the parameters of blood flow may provide early evidence of pathologic processes. Imaging of stable xenon gas provides a regional measure of ventilation which, when coupled with measures of flow, provide for a textural analysis regional of ventilation-perfusion matching. CONCLUSION: With the improved resolution and speed of CT imaging, the patchy nature of regional parenchymal pathology can be imaged as texture of structure and function. With careful control of imaging protocols and the use of objective image analysis methods it is possible to provide site-independent tools for the assessment of interstitial lung disease. There remains a need to validate these methods, which requires interdisciplinary and cross-institutional efforts to gather appropriate data bases of images along with a consensus on appropriate ground truths associated with the images. Furthermore, there is the growing need for scanner manufacturers to focus on not just visually pleasing images, but on quantitatifiably accurate images.     

Iatrogenic FDG foci in the lungs: a pitfall of PET image interpretation

Ohne Zusammenfassung     

TEL/PDGFbetaR induces hematologic malignancies in mice that respond to a specific tyrosine kinase inhibitor

The TEL/PDGFbetaR fusion protein is expressed as the consequence of a recurring t(5;12) translocation associated with chronic myelomonocytic leukemia (CMML). Unlike other activated protein tyrosine kinases associated with hematopoietic malignancies, TEL/PDGFbetaR is invariably associated with a myeloid leukemia phenotype in humans. To test the transforming properties of TEL/PDGFbetaR in vivo, and to analyze the basis for myeloid lineage specificity in humans, we constructed transgenic mice with TEL/PDGFbetaR expression driven by a lymphoid-specific immunoglobulin enhancer-promoter cassette. These mice developed lymphoblastic lymphomas of both T and B lineage, demonstrating that TEL/PDGFbetaR is a transforming protein in vivo, and that the transforming ability of this fusion is not inherently restricted to the myeloid lineage. Treatment of TEL/PDGFbetaR transgenic animals with a protein tyrosine kinase inhibitor with in vitro activity against PDGFbetaR (CGP57148) resulted in suppression of disease and a prolongation of survival. A therapeutic benefit was apparent both in animals treated before the development of overt clonal disease and in animals transplanted with clonal tumor cells. These results suggest that small-molecule tyrosine kinase inhibitors may be effective treatment for activated tyrosine kinase-mediated malignancies both early in the course of disease and after the development of additional transforming mutations.     

Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients

Background  

Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+)-patients with D(+) or D(-) donors.     

Downregulation of 14-3-3sigma in ovary, prostate and endometrial carcinomas is associated with CpG island methylation.

The 14-3-3sigma inhibitor of cell cycle progression has been shown to be target of epigenetic deregulation in many forms of human cancers; however, its role in urological and gynecological cancers has not been studied. Here, we have analyzed the expression of 14-3-3sigma, wild-type p53 and mutated p53 in over 300 cases of the most common cancers occurring in the urological and gynecological tracts and its normal counterpart tissue by immunohistochemistry using the multiple tumor tissue microarrays. 14-3-3sigma expression was detected in normal epithelia from most organs with sporadic expression in renal tubules and absence in the testis. In contrast to normal tissue, 14-3-3sigma expression was lost in 40-60% of adenocarcinomas of the breast, ovary, endometrium and prostate. There was no association between 14-3-3sigma and wild-type/mutated p53 expression. By performing methylation-specific PCR, we showed a close association of 14-3-3sigma CpG island methylation and low protein expression levels of 14-3-3sigma. In addition, a direct link of 14-3-3sigma mRNA expression levels to CpG island methylation is demonstrated in two human cancer cell lines. Loss of 14-3-3sigma expression due to promoter hypermethylation may represent the most frequent molecular aberration in ovarian, endometrial and prostate adenocarcinomas.     

Oral administration of 17beta-estradiol over 3 months without progestin co-administration does not improve coronary flow reserve in post-menopausal women: a randomized placebo-controlled cross-over CMR study.

BACKGROUND: Several large epidemiological outcome studies did not demonstrate a benefit of combined estrogen-progestin replacement treatment (HRT) on cardiovascular events in elderly postmenopausal women. Whether progestin antagonism is responsible for these negative results or the natural estrogen 17ss-estradial (E2) itself is not effective in the coronary circulation is unknown. AIM: To assess the effect of 3 months of E2 treatment on the coronary circulation, i.e., on coronary flow reserve (CFR), in postmenopausal women without established coronary artery disease (CAD). METHODS: In a double-blind placebo-controlled cross-over design postmenopausal women (60 +/- 5 years, n = 14) were randomized to either start with placebo or E2 (Estrofem, Novo Nordisk, Copenhagen, Denmark) 2 mg/d given orally over 3 months and to switch thereafter for another 3 months of therapy. At baseline, a stress echocardiography was performed to exclude CAD. CFR was determined by coronary sinus CMR flow measurements (with motion-adapted gating and interactive acquisition window control; spatial/temporal resolution of 0.8 x 0.9 mm2/25-30 ms) which were performed at rest and during vasodilation (dipyridamole 0.56 mg/kg over 4 minutes IV) at baseline, and after 3 and 6 months of therapy, respectively. RESULTS: Hemodynamics such as heart rate and systolic and diastolic blood pressure were not different for the control and E2 group. For CFR and for resting and hyperemic coronary sinus blood flow, no differences between the placebo and E2 group were found (2-way ANOVA for repeated measurements). Reproducibility of phase-contrast CMR measurements of CFR was -1.1 +/- 4.9%. CONCLUSIONS: In elderly postmenopausal women without significant CAD, oral administration of E2 over 3 months without a progestin co-administration does not improve CFR. This finding yields partly explanation for some large epidemiological trials which could not demonstrate a clinical cardiovascular benefit of HRT in elderly women.     

Preventing Implant-Associated Infections by Silver Coating

Implant-associated infections (IAIs) are a dreaded complication mainly caused by biofilm-forming staphylococci. Implant surfaces preventing microbial colonization would be desirable. We examined the preventive effect of a silver-coated titanium-aluminum-niobium (TiAlNb) alloy. The surface elicited a strong, inoculum-dependent activity against Staphylococcus epidermidis and Staphylococcus aureus in an agar inhibition assay. Gamma sterilization and alcohol disinfection did not alter the effect. In a tissue cage mouse model, silver coating of TiAlNb cages prevented perioperative infections in an inoculum-dependent manner and led to a 100% prevention rate after challenge with 2 × 10⁶ CFU of S. epidermidis per cage. In S. aureus infections, silver coating had only limited effect. Similarly, daptomycin or vancomycin prophylaxis alone did not prevent S. aureus infections. However, silver coating combined with daptomycin or vancomycin prophylaxis thwarted methicillin-resistant S. aureus infections at a prevention rate of 100% or 33%, respectively. Moreover, silver release from the surface was independent of infection and occurred rapidly after implantation. On day 2, a peak of 82 μg Ag/ml was reached in the cage fluid, corresponding to almost 6× the MIC of the staphylococci. Cytotoxicity toward leukocytes in the cage was low and temporary. Surrounding tissue did not reveal histological signs of silver toxicity. In vitro, no emergence of silver resistance was observed in several clinical strains of staphylococci upon serial subinhibitory silver exposures. In conclusion, our data demonstrate that silver-coated TiAlNb is potent for prevention of IAIs and thus can be considered for clinical application.