Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

Verletzungen der Handwurzel

A fall onto the hand can be followed by ligament ruptures, bone fractures or dislocated fractures of the carpus. The diagnosis is based on history, clinical evaluation, and X-ray examination in two perpendicular planes, followed if necessary by CT scan or MRI scan. Lesions of the scapholunate ligaments cannot be definitely excluded except by arthroscopy. As well as fractures of the carpometacarpal joints, fractures involving the ring structure of the carpus or ligament ruptures between carpal bones are frequently observed, and these lead to significantly impaired biomechanics. The prognosis is poor. The discontinuity of the ring must be repaired by means of osteosynthesis and/or suturing ligaments, with the carpal bones held in place by temporary arthrodesis using K-wires. Dislocation in this region requires rapid realignment, as untreated perilunate dislocation or dislocation of the lunate bone will lead to serious secondary damage, which can only be treated by salvage operations involving loss of function. Inappropriate treatment of an injury to the heel of the hand can lead to carpal collapse.     

Thoraxtrauma

Chest injuries can be sustained in isolation or in association with multiple injuries. Life-threatening complications may ensue because organs that are vital to survival of the organism are situated within the thoracic cavity. These complications include airway obstruction, tension pneumothorax, wide open pneumothorax, flail chest, cardiac tamponade and massive hemothorax. The mortality of patients hospitalized with chest injury can be as high as 10%. Clinical examination and awareness of the possibility of other injuries (high level of suspicion) are essential, and standard chest X-ray, ultrasound and thoracic computed tomography may also be needed for the diagnosis. The first part of this serial paper on the management of chest injuries focuses on anatomical aspects, pathophysiology and symptoms, but mainly on the indications for the standard diagnostic procedures and further high-tech examinations.     

IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Severe community-acquired pneumonia due to Legionella pneumophila Serogroup 6.

Legionella pneumophila is a common cause of sporadic community-acquired pneumonia, but culture-proven legionellosis is rarely diagnosed. There is no laboratory test for Legionnaires' disease that can detect all patients with the disease. Culture is the standard diagnostic method and should be initiated as soon as possible in suspected cases. We describe a rare case of community-acquired pneumonia caused by L. pneumophila serogroup 6. A 77-year-old man was admitted to a tertiary care hospital because of high fever, productive cough, and progressive dyspnea. Chest radiography showed bilateral pneumonia, which led to respiratory failure necessitating mechanical ventilatory support. Despite antibiotic therapy, his condition continued to deteriorate and acute renal failure also developed. Urine was negative for L. pneumophila. Culture of the sputum yielded L. pneumophila serogroup 6, although there was no elevation of the serum antibody titer. Pneumonia resolved gradually and he was extubated after treatment with levofloxacin followed by erythromycin. L. pneumophila other than serogroup 1 should be included in the differential diagnosis of patients with suspected atypical community-acquired pneumonia.     

Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis.

OBJECTIVES: To determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle. PATIENT AND METHODS: This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n = 25) and luteal (n = 10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n = 7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods. RESULTS: Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expression was negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle. CONCLUSION: Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.     

Endometrial cancer patients have a significant risk of harboring isolated tumor cells in histologically negative lymph nodes

In this study, we examine the prevalence of finding isolated tumor cells (ITCs) in negative lymph nodes of endometrial cancer patients using immunohistochemistry. Seventy-six endometrial cancer patients with lymph nodes histologically negative for metastatic disease were examined. Nodal tissue sections were stained with anticytokeratin antibodies AE-1 and CAM 5.2. Nodes with single or groups of cells (two to four cells) < or =0.2 mm and showing cytokeratin reactivity were positive for ITCs. Findings were compared to features of the primary tumor and patient outcome. ITCs were present in 31 of 1712 lymph nodes. Fifteen (19.7%) patients had ITC-positive nodes. ITCs involved only pelvic nodes in nine cases, only para-aortic nodes in five cases, and pelvic and para-aortic in one case. Tumor in adnexa was the only pathologic feature associated with nodal ITCs (P= 0.0485). All 15 patients with nodal ITCs were alive at follow-up. One (6.7%) patient suffered recurrent disease but was alive at last encounter. Disease recurred in 5 (8.8%) of 57 patients without nodal ITCs. Two are alive without disease, two alive with disease, and one died from her cancer. In summary, a significant proportion of endometrial cancer patients have ITCs detected by immunohistochemistry in histologically negative regional lymph nodes.