Function of the vascular endothelial growth factor receptors Flt-1 and Flk-1/KDR in the alloimmune response in vivo

BACKGROUND: We have recently reported that vascular endothelial growth factor (VEGF) functions as a proinflammatory cytokine to regulate the trafficking of leukocytes into allografts in the early posttransplant period. VEGF binds two major VEGF receptors: VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR). Here, we wished to investigate the expression and function of VEGF receptors in the process of acute allograft rejection in vivo. METHODS: We performed fully MHC-mismatched C57BL/6 (H-2b) into BALB/c (H-2d) vascularized heterotopic murine cardiac transplants and we examined the expression of VEGF and VEGF receptors by immunohistochemistry during acute allograft rejection. Next, we treated mice with specific neutralizing monoclonal antibodies against murine VEGFR-1 and VEGFR-2 and examined their effect on the development of acute allograft rejection by histology and by analysis of graft survival. The intragraft expression of cytokines and chemokines were also evaluated by quantitative real-time PCR analysis. RESULTS: The expression of VEGF, VEGFR-1 and VEGFR-2 were significantly up-regulated during allograft rejection as compared to isografts. Administration of either anti-VEGFR-1 or anti-VEGFR-2 alone failed to inhibit allograft rejection. However, coadministration of both antibodies together inhibited leukocyte infiltration of allografts and prolonged allograft survival. Furthermore, the effect of VEGFR blockade was associated with the downregulation of intragraft cytokine and chemokine expression. CONCLUSIONS: Our data suggest that VEGF-VEGFR interactions function in the alloimmune response in vivo. Targeting VEGFRs may represent a novel therapy to protect allografts following clinical transplantation.     

Detection of the center of the hip joint in computer-assisted surgery: an evaluation study of the Surgetics algorithm.

OBJECTIVE: The aim of this paper is to assess the accuracy of an algorithm implemented by PRAXIM in the SURGETICS navigation station for detection of the hip center. This study will assess the robustness and accuracy of the algorithm in various clinical situations such as those involving non-sphericity of the femoral head, motion of the pelvis during hip center detection, and restricted range of motion. MATERIALS AND METHODS: The localization of the hip center, based on kinematics, relies on the recording of n successive positions of the femoral rigid body in the localizer reference system during a passive circumduction motion of the hip joint. Therefore, the shape of the clouds of points acquired may vary from one acquisition to the next. To allow a comprehensive study of the consequences of these variations for hip center detection, we developed a simulator to generate numerous clouds of points. Results given subsequently for each test are the values of the difference between the femoral mechanical axis computed with C(c), the computed hip center, and the same axis computed with C(o), the reference hip center. RESULTS: Test 1: Sensitivity to noise. The errors ranged from 3.33 E - 12 (SD 3.29E - 12) for a noise of 0 mm to 8.18E - 1 (SD - 7.05E - 1) for a noise of 15 mm. Test 2: Sensitivity to the shape of the acquisition motion. All trajectories gave an error < 1 degrees . Test 3: Sensitivity to restricted range of motion. No value > 1 degrees was found during this test. Test 4: Sensitivity to the distance between two points of the cloud. No value > 0.5 degrees was found during this test. Test 5: Sensitivity to the number of points included in the cloud. No value > 1 degrees was found during this test. CONCLUSIONS: The Surgetics algorithm is robust to noise, can compensate for pelvic motion, and can be used even in the case of restricted range of motion.     

Bone marrow biopsy involvement by non-Hodgkin's lymphoma: frequency of lymphoma types, patterns, blood involvement, and discordance with other sites in 450 specimens

To evaluate the features of bone trephine biopsy involvement by non-Hodgkin lymphoma, 450 specimens were evaluated for percentage of marrow involvement, pattern of involvement, presence of germinal centers or follicular structures, and discordance with other involved sites. A subset of 197 cases was evaluated for evidence of concurrent peripheral blood involvement. Follicular grade 1 lymphoma (30.4%) was the most common type to involve the marrow, followed by diffuse large B-cell lymphoma (16.0%), mantle cell lymphoma (9.3%), low-grade B-cell lymphoma, not otherwise specified (8.7%), lymphoplasmacytic lymphoma (8.4%), follicular grade 2 lymphoma (7.1%), and mature T- and NK-cell lymphomas (6.4%). A mixed pattern of infiltration was most common, followed by paratrabecular, nodular, diffuse, and interstitial patterns. Greater than 90% of follicular lymphomas had at least a focal paratrabecular infiltration pattern, but this pattern was also seen with other lymphoma types. Interstitial disease infiltration tended to correlate with lymphoplasmacytic lymphoma but was also not specific. The presence of germinal centers or follicular structures was associated with follicular lymphoma in 88% of cases. Discordance between the bone marrow morphology and other tissue sites was observed in 24.9% of cases and was most often seen with follicular or diffuse large B-cell lymphoma. Peripheral blood involvement by lymphoma was observed in 29% of cases, found in all disease groups except for follicular grade 3 lymphoma. This study highlights the frequency of different lymphoma patterns in the marrow, limitations of primary lymphoma classification on biopsy material alone, and the relative frequency of marrow discordance and peripheral blood involvement by marrow lymphoma.     

Can phlebectomy be deferred in the treatment of varicose veins?

OBJECTIVE: This study was designed to observe the clinical sequelae of varicose veins after great saphenous vein (GSV) ablation and to assess possible predictability of spontaneous varicose vein regression. METHODS: Patients with symptomatic varicose veins secondary to GSV insufficiency treated with radiofrequency ablation (RFA) were enrolled in the study. Up to five of the largest varicose veins in each limb were mapped, sized, and documented before RFA. No varicose vein was treated either at the time of RFA or within 6 months postoperatively. Varicose vein status was recorded at follow-up visits. RESULTS: Fifty-four limbs in 45 patients were included. A total of 222 varicose veins were documented before RFA (4.1 +/- 1.1 varicose veins per limb) with an average size of 11.4 +/- 3.7 mm. During the follow-up period, complete resolution of visible varicose veins was seen in 13% of limbs after RFA alone, and 63 (28.4%) varicose veins spontaneously resolved. A further 88.7% (141/159) of varicose veins decreased in size an average of 34.6% (4.3 +/- 3.4 mm). Preoperatively, 19.4% of varicose veins were above the knee and 75.7% were below the knee. Complete varicose vein resolution was 41.9% (18/43) above the knee and 25.6% (43/168) below the knee. For the above-knee varicose veins, 88.4% (38/43) were located medially, and all the resolved ones (47.4%, 18/38) were medial varicose veins. Resolution rates of the 168 below-knee varicose veins were 30.6% (33/108) of medial, 23.1% (6/26) of anterior, 20.0% (3/15) of lateral, and 5.3% (1/19) of posterior. CONCLUSIONS: Great saphenous vein ablation resulted in subsequent resolution or regression of many lower-limb visible varicose veins. With further study, the predictability of varicose vein regression may perhaps be increased, which can then direct the treatment strategy to further leverage the advantages of minimally invasive endovenous procedures.     

Composite resin in medicine and dentistry

Composite resin has been used for nearly 50 years as a restorative material in dentistry. Use of this material has recently increased as a result of consumer demands for esthetic restorations, coupled with the public's concern with mercury-containing dental amalgam. Composite is now used in over 95% of all anterior teeth direct restorations and in 50% of all posterior teeth direct restorations. Carbon fiber reinforced composites have been developed for use as dental implants. In medicine, fiber-reinforced composites have been used in orthopedics as implants, osseous screws, and bearing surfaces. In addition, hydroxyapatite composite resin has become a promising alternative to acrylic cement in stabilizing fractures and cancellous screw fixation in elderly and osteoporotic patients. The use of composite resin in dentistry and medicine will be the focus of this review, with particular attention paid to its physical properties, chemical composition, clinical applications, and biocompatibility.     

Preservation of Muscular and Elastic Artery Distensibility After an Intercontinental Cryoconserved Exchange: Theoretical Advances in Arterial Homograft Generation and Utilization

While the situation of tissue donation and transplantation differs between Latin American and European countries, a common problem is tissue deficiency. Hence, at present, there is a pressing need to generate alternatives so as to increase the possibilities of obtaining the requested materials. Consequently, it would be of significant interest to establish an intercontinental network for tissue exchange, to improve international cooperation, and to help patients that need tissue transplantation, and to evaluate the feasibility of using an intercontinental network for the exchange of cryopreserved arteries (cryografts), preserving the arterial distensibility and ensuring a reduced native artery–cryograft biomechanical mismatch. Distensibility was studied in ovine arteries divided into three groups: intact (in vivo tests, conscious animals), fresh control (in vitro tests immediately after the artery excision, Uruguay), and cryografts (in vitro tests of cryopreserved-transported-defrosted arteries, Spain). Histological studies were performed so as to analyze changes in the endothelial layer and elastic components. The comparison between fresh control and cryografts showed that neither the cryopreservation nor the exchange network impaired the distensibility, despite the expected histological changes found in the cryografts. The comparison between intact and cryografts showed that the cryografts would be capable of ensuring a reduced biomechanical mismatch. The cryopreservation and the intercontinental network designed for artery exchange preserved the arterial distensibility. It could be possible to transfer cryografts between Latin America and Europe to be used in cardiovascular surgeries and/or for tissue banking reprocessing, with basic biomechanical properties similar to those of the fresh and/or native arteries.     

肾小球足细胞裂孔膜蛋白在肾移植大鼠慢性移植肾肾病中的作用

进展性蛋白尿和肾小球硬化是慢性移植肾肾病(chronic allograft nephropathy, CAN)的特征性表现.足细胞是蛋白尿最主要的物理和电荷屏障,它的损伤可导致蛋白尿和肾小球硬化.尽管足细胞在局灶节段性肾小球硬化、膜性肾病、微小病变和糖尿病肾病中的地位已经得到证实,但是其在CAN中的作用机制目前仍知之甚少.美国研究者利用大鼠肾移植模型试图解释足细胞损伤在CAN中的作用.     

Arteriovenous fistula of the superior gluteal artery as a complication of posterior iliac crest bone graft harvesting: 3D-CT angiography and arterial embolization

Superior gluteal artery injuries are rare, but potentially serious complications that occur during posterior iliac crest bone graft harvesting. The authors reported an arteriovenous fistula of the superior gluteal artery, which occurred as a complication during posterior iliac crest bone graft harvesting and was diagnosed with 3D-CT angiography, then treated with arterial embolization.     

Intramuscular myxoma of the cervical paraspinal muscle

Myxoma is a neoplasm of mesenchymal origin composed of undifferentiated stellate cells in a myxoid stroma. This tumor can develop in a variety of locations. Myxomas that arise from skeletal muscles are called intramuscular myxomas. They usually occur in large skeletal muscles. Only ten cases of these benign tumors involving the neck muscles were reported in literature. Of them, only three were located at the paraspinal muscles. A 64-year-old woman presented with occiptal and neck pain over 5 years noted an expansive painful lesion located at posterior cervical region with progressive volume increase in the last 12 months. Image exams revealed a large mass located in the left posterior region of the neck in contact with the C2, C3 and C4 laminae with no invasion of the vertebrea. Tumor total removal was performed through normal muscle margins and the vertebral periosteum was scraped. The tumor was encapsuleted, lobulated with a gray-white appearance. The histological examination yielded the diagnosis of intramuscular myxoma. Follow-up at 1 year showed complete resolution of preoperative symptoms and no evidence of local recurrence. In conclusion, although rare, intramuscular myxoma should be included in differential diagnosis of cervical paraspinal tumors. We reported the fourth case of intramuscular myxoma in the paraspinal musculature of the neck. Despite its benign characteristics, local recurrence was reported after subtotal resection. Tumor total removal should be the goal of surgery.     

Ligament Tension in the ACL-deficient Knee: Assessment of Medial and Lateral Gaps

Obtaining symmetric and balanced gaps under equilateral loads is a common goal in posterior cruciate ligament (PCL)-retaining and -sacrificing TKAs. Owing to limitations in existing surgical tensors, however, tensing knee ligaments with standardized and symmetric loads has been possible only with the patella subluxated or everted. We therefore determined the influences of (1) patellar eversion versus complete reduction, (2) PCL resection, and (3) load magnitude on gap symmetry and balance in the anterior cruciate ligament (ACL)-deficient knee. We used a novel computer-controlled tensioner to measure gaps in 10 cadavers with an applied force of 50 N, 75 N, and 100 N per side. Gap data were acquired at 0o, 30o, 60o, 90o, and 120o flexion with the patella reduced and everted and with the PCL intact and resected. Everting the patella tightened the medial and lateral flexion gaps between 90o and 120o by 0.7 mm to 2.7 mm. PCL resection increased gaps from 30° to 120° by 1 mm to 3 mm. Increasing the force from 50 N to 100 N increased the mean gap by 0.5 mm. Everting the patella and resecting the PCL influenced gap balance and symmetry. Surgeons should be aware of how these conditions affect gaps during assessment and balancing. Richard Laskin—Deceased. One of the authors (CP) is employed by Praxim Inc, Walpole, MA. Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.