Citations

Abstract Frequently, meniscal pathology accompanies degenerative changes affecting the articular surface of the knee. The attritional changes in the meniscus lead to fragmentation of the meniscus and a variety of tears, usually of the posterior horn of the medial meniscus. A prospective study of the results of arthroscopic partial meniscectomy in the presence of at least Outerbridge Grade III chondromalacia of the accompanying joint surface was performed between 1980 and 1984. Eighty‐seven knees in 84 patients were studied. The mean age was 62 (29–84) years. The right knee was involved in 44 patients, and 47 were men. Preoperative radiographs demonstrated osteoarthritis in 53 patients. The medial meniscus was involved in 82, while the lateral meniscus was affected in nine knees. Four knees had involvement of both menisci. In 72 knees, the most frequent lesion was a tear of the posterior horn of the medial meniscus. The most frequent configuration of the tears was a flap in 42. The morbidity was small with the use of ambulatory aids being 10 ± 13 (mean ± SD) days. Subsequent surgery was performed on six knees consisting of two total knee arthroplasties, two upper‐tibial osteotomies, one repeat arthroscopic meniscectomy, and one popliteal cyst excision. Two patients had poor results related to progression of their arthritis and one developed osteonecrosis. Five patients were unchanged from their preoperative status. Subchondral sclerosis or osteophytes on the preoperative radiographs correlated with 72% compared to 90% satisfactory results in the absence of these findings (p < 0.03). Complications consisted of superficial thrombophlebitis in three, hemarthrosis in one, and superficial infection in one patient. Arthroscopic meniscectomy is a valuable adjunct to the management of the older patient with early degenerative arthritis of the knee and symptomatic meniscus tears.

Abstract The use of high energy devices has been suggested for intra‐articular surgery. Experimental studies have been performed using the laser and electrocautery. However, clinical application has primarily been with the use of the electrocautery. Electrosurgery is currently being used for lateral retinacular release as well as meniscal surgery. Inadvertent damage to articular cartilage may occur, especially during meniscal resection. The objective of the current study is to assess the effect of the Concept electrocautery with the meniscal cutting electrode on fresh human articular cartilage. Twenty fresh tibial plateaus removed at the time of total knee arthroplasty were subjected to electrocautery currents ranging from 25 to 82.5 W. The articular cartilage was stained with hematoxylin and eosin. The extent of cartilage necrosis was quantitated as a percentage of the thickness of the articular cartilage. A dose response curve was developed. The extent of articular cartilage necrosis with the electrocautery setting of 20 (24.4 W) commonly used for meniscal resection resulted in only an 11.4%‐injury to the articular cartilage. At the manufacturer's recommended setting of 24 (27 W), a 16% depth of laceration of the articular cartilage may be anticipated. We conclude that the lowest current setting possible should be utilized for meniscal surgery and the risk of articular cartilage damage from inadvertent injury is not excessive.

Background and Purpose— Women have poorer outcomes from stroke than men. Women also have risk factors that are unique, including pregnancy and hormone therapy. Hormone therapy for postmenopausal replacement increased the risk of ischemic stroke according to results of the Women’s Health Initiative clinical trials. Based on the current understanding of the mechanisms of action of estrogen, the reasons for this increased risk are uncertain. One method to better understand the reasons for this increased risk is to re-evaluate estrogen’s role in the neurovascular unit, simplistically comprised of the neurons, glia, and endothelial cells, as well as the processes of inflammation, and hemostasis/thrombosis. Besides the role of estrogen there are many gaps of knowledge about issues specific to women and stroke. Summary of Review— A multidisciplinary workshop was held in August 2005 to summarize the current evidence for estrogen and, more generally, stroke in women, and to provide recommendations for future basic, preclinical, and clinical research studies. Conclusions— These studies may ultimately change the approach to stroke prevention and treatment in women.

Abstract In spite of recent advances in molecular biology leading to the introduction of clinically active novel agents, such as imatinib, erlotinib, and bevacizumab, therapy of the most common epithelial tumors, such as lung cancer, remains unsuccessful. The diversity of molecular abnormalities in these tumors is felt to partly contribute to their resistance to therapy. It is, therefore, widely accepted that one approach to improving the efficacy of cancer therapy is the development of rational, hypothesis-based combinations of anticancer agents that may exhibit synergistic cytotoxic interactions. A number of empirical combination studies with the epidermal growth factor receptor and classic cytotoxic agents were undertaken in clinical trials, with disappointing results. It is, therefore, felt that preclinical combinations of epidermal growth factor receptor inhibitors and other novel agents, based on sound knowledge of complementary signaling pathways whose concerted inhibition would be hypothesized to inhibit growth, is the reasonable approach in the future. A brief overview of some of these pathways (mammalian target of rapamycin, vascular endothelial growth factor receptor, and ras/mitogen-activated protein kinase signaling) is provided in this review.

AbstractRadioligand binding has been used for many years to identify new binding sites, characterize receptors, and identify novel ligands. Although various techniques have been developed to improve the efficiency of preparing the biological source of the receptors and for detecting bound radioligand, the principles of the assays remain the same. This unit reviews theory and provides examples of the parameters that can be calculated from radioligand binding data to characterize ligand‐receptor interactions. The important aspects of assay development and validation that allow meaningful interpretation are discussed. The selection of a radioligand, buffer and other assay components is critical to developing a useful binding assay. The nature of the binding interaction can also be probed by varying assay conditions.

Abstract Purpose: Although metastasis is the primary determinant of poor survival of patients with osteogenic sarcoma, some patients live much longer than others, indicating metastatic heterogeneity underlying survival outcome. The purpose of the investigation was to identify genes underlying survival outcome of patients with osteogenic sarcoma metastasis. Experimental Design: We have used microarray to first compare mRNA expression between normal bone and osteogenic sarcoma specimens, identified genes overexpressed in osteogenic sarcoma, and compared expression of the selected gene between a poorly metastatic (SAOS) and two highly metastatic cell lines (LM8 and 143B). Finally, expression of the selected gene was assessed by immunostaining of osteogenic sarcoma samples with known survival outcome. Results: Microarray analysis revealed 5.3-fold more expression of WT1 mRNA in osteogenic sarcoma compared with normal bone and &gt;2-fold overexpression in 143B and LM8 cells compared with SAOS. Furthermore, WT1 mRNA was absent in normal bone (10 of 10) by reverse transcription-PCR but present in osteogenic sarcoma–derived cell lines (5 of 8). One hundred percent (42 of 42) of low-grade osteogenic sarcoma specimens expressed no WT1 as determined by immunostaining; however, 24% (12 of 49) of the high-grade specimens showed intense staining. Mean survival of patients with high-grade metastatic osteogenic sarcoma but low WT1 staining (27 of 37) was 96.5 ± 129.3 months, whereas mean survival of patients with high-grade metastatic osteogenic sarcoma having intense staining (10 of 37) was 18.3 ± 12.3 months (P &gt; 0.0143). All splice variants of WT1 mRNA, including a hitherto unknown variant (lacking exons 4 and 5), were found to be expressed in osteogenic sarcoma. Conclusion: WT1 seems to be associated with very poor survival of patients with osteogenic sarcoma metastasis.

Abstract Overexpression of fibroblast growth factor receptor 3 (FGFR3) is a hallmark of t(4;14) multiple myeloma (MM). To dissect the mechanism of FGFR3 oncogenesis in MM, we used 3 FGFR selective kinase inhibitors—CHIR258, PD173074, and SU5402—and FGFR3-specific siRNA to modulate FGFR3 activity. Conversely, the ligand FGF was used to stimulate FGFR3 function in human MM cells. The transcriptional response to FGFR3 modification was recorded, and gene expression changes common to all 5 modifiers were documented. Ten genes were commonly regulated. Macrophage inflammatory protein-1 alpha (MIP-1α) was the single most differentially altered gene. MIP-1 α promoter function, gene expression, and protein secretion were each down-regulated following inhibition of FGFR3 signaling. Down-regulation of MIP-1 α was not, however, observed following FGFR3 inhibition in MM cells with RAS mutations implicating RAS-MAPK in MIP-1 α regulation. As confirmation, inhibition of ERK1 also down-regulated MIP-1 α in FGFR3 inhibitor-resistant cells harboring RAS mutations. MIP-1 α is implicated in the survival and proliferation of MM cells and the pathogenesis of MM bone disease. Our observation is the first to directly link an initiating IgH translocation not only to MM-cell growth and survival but also to the disease-associated bone disease.