Combined treatment with αMSH and methylprednisolone fails to improve functional recovery after spinal injury in the rat

To date, relatively little progress has been made in the treatment of spinal cord injury (SCI)-related neurological impairments. Until now, methylprednisolone (MP) is the only agent with clinically proven beneficial effect on functional outcome after SCI. Although the mechanism of action is not completely clear, experimental data point to protection against membrane peroxidation and edema reduction. The melanocortin melanotropin is known to improve axonal regeneration following sciatic nerve injury, and to stimulate corticospinal outgrowth after partial spinal cord transection. Recently, we showed that intrathecally administered αMSH had beneficial effects on functional recovery after experimental SCI. Since both drugs have shown their value in intervention studies after (experimental) spinal cord injury (ESCI), we decided to study the effects of combined treatment. Our results again showed that αMSH enhances functional recovery after ESCI in the rat and that MP, although not affecting functional recovery adversely by itself, abolished the effects observed with αMSH when combined. Our data, thus, suggest that the mechanism of action of MP interferes with that of αMSH.     

Primary retroperitoneal myxoid/round cell liposarcoma is a nonexisting disease: an immunohistochemical and molecular biological analysis

Almost all primary retroperitoneal liposarcomas can be classified as well-/dedifferentiated liposarcoma. Rarely, however, primary retroperitoneal liposarcoma is classified as myxoid/round cell liposarcoma, based on the presence of myxoid areas and vascular crow's feet pattern, which has resulted in a debate on the classification of liposarcoma in the retroperitoneum. Genetically, myxoid/round cell liposarcoma and well-/dedifferentiated liposarcoma are different diseases. Myxoid/round cell liposarcoma is characterized by a translocation causing FUS-CHOP or EWSR1-CHOP fusion, whereas well-/dedifferentiated liposarcoma is characterized by an amplification of the 12q13-15 region, including MDM2 and CDK4 genes. As myxoid/round cell liposarcoma is highly radio- and chemosensitive, differentiation between subtypes is important to optimize treatment. We studied whether primary retroperitoneal liposarcomas diagnosed as myxoid/round cell liposarcoma represent molecularly true myxoid/round cell liposarcoma or are histopathological mimics and represent well-/dedifferentiated liposarcoma. Primary retroperitoneal myxoid/round cell liposarcoma (n=16) were compared to primary extremity myxoid/round cell liposarcoma (n=20). Histopathological and immunohistochemical features were studied. Amplification status of the 12q13-15 region was studied using a multiplex ligation-dependent probe amplification analysis, and FUS-CHOP or EWS-CHOP translocations were studied using RT-PCR. In primary retroperitoneal myxoid/round cell liposarcoma, MDM2 and CDK4 staining was both positive in 12 of 15 cases. In primary extremity myxoid/round cell liposarcoma, MDM2 was negative in 18/20 and CDK4 was negative in all cases. Multiplex ligation-dependent probe amplification showed the amplification of 12q13-15 region in 16/16 primary retroperitoneal myxoid/round cell liposarcomas and in 1/20 primary extremity myxoid/round cell liposarcomas. Translocation was present in all (18/18) primary extremity myxoid/round cell liposarcomas, but absent in all primary retroperitoneal myxoid/round cell liposarcomas. On the basis of immunohistochemical and molecular characteristics, apparent primary retroperitoneal myxoid/round cell liposarcoma can be recognized as well-/dedifferentiated liposarcoma with morphological features mimicking myxoid/round cell liposarcoma. In these cases, treatment should probably be specifically designed as for well-/dedifferentiated liposarcoma. Moreover, finding of myxoid/round cell liposarcoma translocations in a retroperitoneal localization is highly suggestive of metastasis and should prompt search for a primary localization outside the retroperitoneum.     

A SURVEY OF HOSPITAL MORBIDITY,MORTALITY AND QUALITY OF LIFE FOLLOWING CORONARY ARTERY BYPASS SURGERY IN A UK INDO-ASIAN POPULATION

To survey the in-hospital morbidity, mortality, length of stay in the intensive therapy unit (ITU) and hospital and quality of life in patients of Indo-Asian origin following coronary artery bypass (CABG) surgery, 345 consecutive patients (mean age 58 years; SD 8.9; range 32-88 years) undergoing primary, isolated CABG were studied. Non-elective CABG was undertaken in 41% of patients. The left anterior descending artery (LAD) was grafted in 89%, although in 30% of these the internal mammary artery (IMA) was not used. Following CABG, the hospital morbidity and mortality was within the expected range, although there was a trend towards higher in-hospital mortality in the Parsonnet low risk group of patients. The length of ITU and hospital stay was not prolonged. Using the SF-36 questionnaire in postoperative patients, low quality of life scores were obtained for six of the eight modalities tested including physical functioning, bodily pain and general health perception. The low quality of life scores and IMA usage in Indo-Asians needs to be addressed.     

中药贝母类的研究——ⅩⅦ.贝母鳞叶上表皮显微观察

本文对浙贝母Fritillaria thunbergii Miq.等20种贝母的鳞叶上(内)表皮进行了显微观察,发现种间在表皮细胞形状、大小和垂周壁部位角质栓(cuticular peg)的形状,大小和排列等方面有一定区别,可作为新的鉴别依据。全文除描述外,列出检索表,并附主要特征图。     

Intravenous digital subtraction renal angiography: use in screening for renovascular hypertension

Intravenous digital subtraction renal angiography (DSRA) has been compared with conventional angiography only in small, selected series of hypertensive patients. The authors prospectively examined with intravenous DSRA 94 patients at increased risk for renovascular hypertension and compared these studies with conventional angiography. A stenosis of at least one main renal artery was identified with intravenous DSRA in 22 patients and confirmed in 20 patients. No significant stenoses were seen with conventional angiography in any of the 64 patients in whom lesions were not seen with intravenous DSRA. Since inadequate DSRA studies were considered positive for renal artery stenosis, the sensitivity of intravenous DSRA was 100% (25 of 25); specificity, 93% (64 of 69); positive predictive value, 83% (25 of 30); and negative predictive value, 100% (64 of 64). The authors conclude that intravenous DSRA is a sensitive test for identifying stenosis of the main renal arteries and is appropriate to use as a screening test among patients at increased risk for renovascular hypertension.     

Focal Adhesion Kinase Is Important for Fluid Shear Stress‐Induced Mechanotransduction in Osteoblasts

Mechanical loading of bone is important for maintenance of bone mass and structural stability of the skeleton. When bone is mechanically loaded, movement of fluid within the spaces surrounding bone cells generates fluid shear stress (FSS) that stimulates osteoblasts, resulting in enhanced anabolic activity. The mechanisms by which osteoblasts convert the external stimulation of FSS into biochemical changes, a process known as mechanotransduction, remain poorly understood. Focal adhesions are prime candidates for transducing external stimuli. Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase found in focal adhesions, may play a key role in mechanotransduction, although its function has not been directly examined in osteoblasts. We examined the role of FAK in osteoblast mechanotransduction using short interfering RNA (siRNA), overexpression of a dominant negative FAK, and FAK^?/? osteoblasts to disrupt FAK function in calvarial osteoblasts. Osteoblasts were subjected to varying periods oscillatory fluid flow (OFF) from 5 min to 4 h, and several physiologically important readouts of mechanotransduction were analyzed including: extracellular signal‐related kinase 1/2 phosphorylation, upregulation of c‐fos, cyclooxygenase‐2, and osteopontin, and release of prostaglandin E₂. Osteoblasts with disrupted FAK signaling exhibited severely impaired mechanical responses in all endpoints examined. These data indicate the importance of FAK for both short and long periods of FSS‐induced mechanotransduction in osteoblasts.