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.     

Effects of intranasal 17beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo-controlled clinical trial.

AIM: To compare the effects of 17beta-estradiol given intranasally (intranasal E2) and raloxifene on serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. METHODS: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while the intervention groups were given intranasal E2 (Aerodiol; Servier, Chambray-les-Tours, France) (n = 16) or raloxifene (Evista; Lilly SA, Madrid, Spain) (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. RESULTS: The group receiving intranasal E2 showed a significant decrease in triglyceride levels (p<0.05) and a marked increase in high-density lipoprotein cholesterol levels (p<0.05). No changes in lipid profile were observed in the raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p<0.05). CONCLUSION: Intranasal E2 exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. Raloxifene has a greater impact on fibrinogen than intranasal E2 application.     

Hormone replacement therapy and bleeding disorders.

Bleeding disorders encountered during administration of hormone replacement therapy (HRT) are reviewed. The incidence of bleeding disorders is dependent on the phase of HRT and the age of the patient. In the diagnosis of these bleedings transvaginal sonography and minihysteroscopy are very important methods. Endometrial thickness can be monitored exactly by transvaginal sonography. Outpatient minihysteroscopy without anesthesia results in higher compliance to HRT after the procedure. In hormonal treatment of bleeding disorders during HRT, the sonographically supported progestogen test is very useful and can reduce endometrium thickness. Operative treatments include myoma and polyp resection as well as endometrial ablation. By these methods a high rate of bleeding-free HRT can be reached. The problem of endometrial cancer during HRT is discussed on the basis of new literature and critical statements. The review shows the importance of individual diagnostic and treatment schedules for bleeding disorders during HRT.     

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.     

Rehabilitative Maßnahmen bei Patienten mit Pankreaskarzinom

Rehabilitative and palliative measures in the follow-up care of pancreatic cancer patients will remain the dominant medical focus as long as potentially curative measures (recurrence prophylaxis, early detection and therapy of recurrence) have failed to show a significant survival benefit. Rehabilitative measures are possible for patients undergoing potentially curative as well as palliative treatment. Their aim is to alleviate the negative effects of the cancer and its therapy, not only physically, but also psychologically, socially and vocationally. The spectrum of possible somatic handicaps ranges from metabolic disorders, malnutrition and under-nutrition, as well as gastrointestinal symptoms to pain. Assistance in coping with illness, alleviating fears and depression and strengthening compliance are the main areas which are dealt with in psycho-oncology. Assessment of vocational fitness and the capacity to work depends on tumor location, whether R0 or R1 resection has taken place, the extent of pancreas resection, accompanying illnesses, whether or not adjuvant therapy has been given, and the physical condition of the patient