Favorable treatment outcome in non-Hodgkin's lymphoma patients with "poor" mobilization of peripheral blood progenitor cells.

Our purpose was to evaluate the outcome and costs of high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation in patients with the inability to mobilize sufficient numbers of PBPCs to allow rapid engraftment after PBPC transplantation. We treated 172 consecutive non-Hodgkin's lymphoma (NHL) patients with cyclophosphamide and granulocyte colony-stimulating factor followed by apheresis to collect PBPCs. The cells were separated on a Percoll gradient and purged with monoclonal antibodies and complement. The patients were categorized as "good" mobilizers if a collection of > or =2 x 10(6) CD34+ cells/kg was obtained (n = 138, 80%) or "poor" mobilizers if <2 x 10(6) CD34+ cells/kg were obtained (n = 34, 20%). With a median follow-up of 3.5 years, there is no statistically significant difference in actuarial event-free survival, overall survival, or relapse for good mobilizers compared with poor mobilizers. However, there was a trend toward increasing nonrelapse, transplantation-related mortality of 11.8% for poor mobilizers versus 3.6% for good mobilizers (P = .08) and early death from all causes including relapse within 120 days (poor 20.6% versus good 8.7%, P = .06). The total cost for bone marrow transplantation-related care was significantly higher, at $140,264 for poor mobilizers versus $80,833 for good mobilizers (P = .0001). The population of patients with NHL who mobilize PBPCs poorly into the circulation have a higher cost for posttransplant support. However, there is no significant difference in relapse, event-free survival, or overall survival for such patients compared with those who mobilize PBPCs easily.     

Role of MIF in inflammation and tumorigenesis

MIF has been described as a protein that plays an essential role in both innate and acquired immunity. Previous studies have demonstrated that MIF activates lymphocytes, granulocytes and monocytes/macrophages. Furthermore, MIF can counteract the physiological function of steroids, thus playing a role in immune system regulation. Further evidence for a role of MIF in immunity was obtained in mouse models of autoimmune disorders, where the inhibition of MIF resulted in a more benign disease progression. This observation made MIF an attractive therapeutic target for the treatment of these disorders. Moreover, MIF expression was found to be upregulated in a variety of different tumor cells, a finding that further attracted interest. This review provides an overview of the involvement of MIF in both autoimmune disorders and tumorigenesis and summarizes the molecular action of MIF in this context.     

Glioblastoma initiating cells are sensitive to histone demethylase inhibition due to epigenetic deregulation

Tumor-initiating cells are a subpopulation of cells that have self-renewal capacity to regenerate a tumor. Here, we identify stem cell-like chromatin features in human glioblastoma initiating cells (GICs) and link them to a loss of the repressive histone H3 lysine 9 trimethylation (H3K9me3) mark. Increasing H3K9me3 levels by histone demethylase inhibition led to cell death in GICs but not in their differentiated counterparts. The induction of apoptosis was accompanied by a loss of the activating H3 lysine 9 acetylation (H3K9ac) modification and accumulation of DNA damage and downregulation of DNA damage response genes. Upon knockdown of histone demethylases, KDM4C and KDM7A both differentiation and DNA damage were induced. Thus, the H3K9me3–H3K9ac equilibrium is crucial for GIC viability and represents a chromatin feature that can be exploited to specifically target this tumor subpopulation.     

Powerholders in the church: A psychological profile of Catholic bishops in the United States

Obtained a profile of heads of dioceses. Of 153 ordinaries in the 48 continguous states, 44 volunteered through mail contact, were studied, and were compared through static-group comparison to a national sample of priests (N = 218) and an initial sample of bishops (N = 81), based on responses to the Personal Orientation Inventory, the Identity Scale, the Loyola Sentence Completion Blank for Clergymen, the Self-Anchoring Rating Scale of Maturity of Faith, and a demographic data sheet. Of 16 hypotheses, 8 were supported—none compared groups of bishops. Bishops as compared to priests showed more: Occupational commitment, self-esteem, positive affectual experience, successfully formed identity, expressivity and comfort in social contexts, psychological integrity, autonomy within social limits, and trust. They experienced less overall conflict, and less in regard to self, interpersonal relations, psychosexual maturity, church-faith-religion, priesthood, and job satisfaction. However, they were not more mature in faith, showed less individualistic expressivity, and were less self-actualized than priests—significantly so only as to rigidity in applying values (p <.002).     

Thermal damage during thulium laser dissection of laryngeal soft tissue is reduced with air cooling: ex vivo calf model study

OBJECTIVES: The 2-microm-wavelength thulium laser has recently been shown to be an effective cutting instrument in endolaryngeal surgery, although there is increased thermal trauma as compared with the carbon dioxide laser. This study investigated temperature changes and thermal trauma during thulium laser dissection of laryngeal tissue, with and without air cooling, in an ex vivo model. METHODS: A continuous-wave thulium laser (400-microm fiber, 4-W continuous power, 4-second duration) was used to incise 10 calf vocal folds. Paired cooled and uncooled cuts were made in each fold with a dermatologic cooling device. A thermistor inserted into the glottic subepithelium was used to measure tissue temperatures. Thermal damage was analyzed histologically by measuring the depth of the zone of lactate dehydrogenase inactivation surrounding the mucosal incision. RESULTS: The initial vocal fold temperature averaged 24.3 degrees C without cooling and 4.4 degrees C with cooling. The peak temperature during cutting averaged 59.1 degrees C without cooling and 28.0 degrees C with cooling. The thermal damage zone surrounding the cooled incisions was approximately 27% less than that surrounding the uncooled incisions. CONCLUSIONS: Air cooling can reduce the extent of thermal trauma associated with thulium laser surgery of the vocal folds, and the high-temperature plume generated during laser cutting is effectively cleared.     

Chick chorioallantoic membrane as a model for simulating human true vocal folds

OBJECTIVES: Evolving photoangiolytic laser techniques for treating vocal fold lesions motivated the development of a model for research and surgical training. The chick chorioallantoic membrane (CAM), which is composed of a microvasculature suspended within the egg albumen, simulates the vocal fold microcirculation within the superficial lamina propria (SLP). To characterize this model, we compared measurements of vessel diameters to superficial vessels in human vocal folds. METHODS: The diameters of first-, second-, and third-order CAM vessels were measured in fertilized chicken eggs. The superficial blood vessels of the human vocal fold were measured from intraoperative images. RESULTS: According to the branching pattern, vessel segments were identified as first-, second-, or third-order, with average diameters of 0.035 mm (0.02 to 0.1 mm), 0.18 mm (0.12 to 0.41 mm), and 0.8 mm (0.6 to 0.98 mm), respectively. The total vessels measured included 362 first-order, 119 second-order, and 82 third-order vessels. In 10 adult human vocal folds, an average vessel diameter of 0.04 mm (0.015 to 0.1 mm) was observed in 50 vessels. CONCLUSIONS: The CAM microvasculature suspended in albumen provides a useful surgical model simulating the microcirculation within the SLP of the human vocal fold. Although first-order CAM vessels best approximate the size of normal vocal fold subepithelial vessels seen at surgery, second- and third-order vessels resemble the vascular abnormalities frequently encountered during microsurgery for phonotraumatic lesions.     

Quantitative and comparative studies of the vocal fold extracellular matrix. I: Elastic fibers and hyaluronic acid

OBJECTIVES: This study examines the elastic fiber and hyaluronic acid (HA) content of the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. METHODS: Lamina propria elastin was quantified by measuring the amino acid desmosine, and HA was measured by an enzyme-linked immunosorbent assay-based technique. Quantitative histology was used to evaluate elastin and HA levels in specific LP regions. The distributions of fibrillin-1, a primary microfibrillar component of elastic fibers, and of tropoelastin, an indicator of elastin synthesis, were immunohistochemically analyzed. RESULTS: Elastin and HA constituted 8.5% +/- 2.1% and 0.82% +/- 0.11% of human LP, respectively, relative to tissue total protein. Although the mean LP desmosine levels were similar across species, the mean HA levels in canine (p < 3.1 x 10(-5)), porcine (p < 1.5 x 10(-5)), and ferret (p < 6.6 x 10(-4)) LPs were 3 to 4 times higher than that in humans. Marked interspecies differences in elastin, fibrillin-1, tropoelastin, and HA distributions were observed histologically. CONCLUSIONS: The elastin content of the human LP is roughly twice that of the dermis, whereas the HA content of the human LP is similar to that of the dermis. Although all species had similar levels of desmosine, histologic evaluation indicates that the porcine elastin distribution is most similar to that of the human LP. Fibrillin-1 staining suggests that stress in the human LP may be particularly high in the superior superficial layer, and tropoelastin staining indicates that the rate of LP elastin turnover may vary spatially.     

Imaging the human vocal folds in vivo with optical coherence tomography: a preliminary experience

OBJECTIVES: Optical coherence tomography (OCT) and polarization-sensitive OCT (PS-OCT) are promising noninvasive methods for in vivo, cross-sectional imaging of the microstructure of the vocal folds. Previous studies in other tissues have shown an axial resolution of less than 10 microm and a maximum imaging depth of about 2 mm. The objectives of this pilot study were to obtain images from the vocal folds of subjects who were being evaluated and/or treated for vocal fold disease and to evaluate how well normal and pathologic microstructure could be seen in these images. METHODS: Twenty-six vocal folds in 13 subjects were imaged with a flexible OCT probe. The images were successfully collected from subjects who were either topically anesthetized or under general anesthesia for microlaryngoscopic procedures. RESULTS: The thickness of the epithelium, the relative collagen content of the subepithelial connective tissue, and certain characteristic features of lesions (including cysts, scarring, and papilloma) were seen in the OCT and PS-OCT images. CONCLUSIONS: "Live microscopy" of the human vocal folds is very promising for improved diagnosis, mapping, and treatment planning. To our knowledge, this study is the first application of PS-OCT for in vivo imaging of the human vocal folds.     

The fate of osteochondral grafts after autologous osteochondral transplantation: a one-year follow-up study in a minipig model

Introduction  Because articular cartilage shows little intrinsic capacity of spontaneous regeneration, a variety of treatment options are currently at use to repair cartilage damage. One of these is the autologous osteochondral transplantation (AOT). The aim of the present work was to study the histological changes during the progress of 1 year after AOT in the knee joint. Materials and methods  Twelve Minipigs underwent an AOT on the medial femoral condyles of both knees using cooled diamond studded trephines with a diameter of the grafts of 4.6 mm. Three animals were sacrificed at each 2, 8, 26 and 52 weeks after the operation. The condyles were analyzed histologically and immunohistologically for collagen types I and II. Results  A successful bony incorporation was observed in all specimens. The transplant demonstrated an increasingly stable integration of the chondral matrix into the cartilage of the surrounding femoral condyle. At 52 weeks after the operations 5 of 6 condyles showed a chondral integration at least at one side of the graft. Immunohistologically all specimens showed physiological staining characteristics up to 52 weeks after operation. The quality of the chondral part of the graft showed a wide range of variations, ranging from vital tissue resembling native cartilage after 52 weeks, to severe degenerative signs beginning 2 weeks after operation and ending at 52 weeks with deep fissures fragmenting the cartilage and the complete loss of vital cells. Conclusion  The press-fit technique allows a stable bony incorporation. A chondral integration of the graft seems to occur, provided that a close contact between the interfaces can be achieved. Present results demonstrate a vital cartilagenous transplant for up to 52 weeks. However, some specimens showed in part severe degenerative signs. A possible explanation is an insufficient cooling of the trephines in relation to the small diameter of the grafts used in the minipig model. The collagen network seems not to be affected for up to 52 weeks. Klaus Baumbach, Jan-Philipp Petersen contributed equally to this work.