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Biomedical subjects

Dror Robinson

Publications and source records attributed to Dror Robinson.

At least 19 recordsLinked to original sources

Repair of articular cartilage lesions in aged chickens by allogeneic transplantation of fresh embryonic epiphyses.

INTRODUCTION: The potential of fresh whole chick epiphyses of embryonic origin to serve as implant material for cartilage defects of aged chicken was tested. MATERIALS AND METHODS: Fresh epiphyses of 11-day-old embryos were collected from 24 animals and transplanted into defects created in the weight-bearing areas of tibiotarsal joint cartilage of 2-year-old chicks. Upon sacrifice, samples were examined macroscopically and microsections were prepared for histology. RESULTS: Macroscopically, control defects remained empty at all the time intervals. Defects of the experimental group were, on the other hand, filled with cartilaginous tissue as early as 2 weeks posttransplantation, although individual epiphyses could still be noted in the implant tissue. At 4 weeks and later, defects were filled with cartilaginous material indistinguishable from hyaline cartilage. Histologically, all grafts remained within the defect's pits, showing mitotic and metabolic activity typical to proliferating hyaline cartilage. The engrafted epiphyses showed a partial incorporation and integration with the surrounding host tissues already at 2 weeks. At 4 weeks and later, the integration was complete. CONCLUSIONS: It is concluded that a chick embryonic epiphyseal cartilage is suitable as a graft source for articular cartilage transplantation. The embryonic epiphyses provide immediate inherent stability to the graft and supply a good mix of mesenchymal progenitor cells responsible for the high rate of cell proliferation and adhesion to the differentiated committed chondrocytes of the host that create the typical favorable chondrogenic milieu. Based on the present findings, it is postulated that human embryonic epiphyses may, in the future, represent an alternative source to the commonly used techniques of hyaline cartilage repair.

Animals↗

Deep vein thrombosis prevention in joint arthroplasties: continuous enhanced circulation therapy vs low molecular weight heparin.

Deep vein thrombosis prevention efficacy using a new, miniature, mobile, battery-operated pneumatic system (continuous enhanced circulation therapy [CECT] system) combined with low-dose aspirin was compared to enoxaparin. One hundred twenty-one patients who underwent total hip or knee arthroplasty were prospectively randomized into 2 groups. The study group was treated by the CECT system starting immediately after the induction of anesthesia. Postoperatively, a daily 100-mg aspirin tablet was added. The control group received 40 mg of enoxaparin per day. Bilateral venography was performed at the fifth to eight postoperative day. In the CECT group, as compared to the enoxaparin group, there was a significantly lower overall rate of DVT and proximal DVT. Safety profiles were similar in both groups. The combination of the CECT device with low-dose aspirin is more effective than enoxaparin in preventing deep-vein thrombosis after lower limb arthroplasties.

Aged↗

Blood rheology in PCA and PCEA after total knee arthroplasty.

The rheological events in 2 groups of patients undergoing total knee arthroplasty were compared--15 patients were given general anesthesia and controlled their postoperative pain applying intravenous patient-controlled analgesia; 17 individuals received combined spinal-epidural anesthesia and controlled their postoperative pain by patient-controlled epidural analgesia (PCEA). Twenty-four and 48 hours after surgery, the patient-controlled analgesia group showed a significant increase in whole-blood viscosity at the 3 shear rates (P < .01), as well as in relative viscosity at both periods (P < .001 and .01, respectively). Similar findings were observed for red blood cell aggregation (P < .001) and fibrinogen level (P < .001). These values were less expressed in the PCEA group, particularly 48 hours after surgery (P < .01), and the patients showed lower scores on the visual analog pain scale. The better results observed in the PCEA group favor the application of epidural anesthesia and PCEA analgesia in patients undergoing total knee arthroplasty.

Aged↗

Use of a novel joint-simulating culture system to grow organized ex-vivo three-dimensional cartilage-like constructs from embryonic epiphyseal cells.

A method for growth and maintenance of vital cartilaginous tissue is necessary for cartilage repair by in-vitro produced biologic implants. A previously tested perfusion system simulating joint activity was used. Whole epiphyses collected from thirty 11-day-old chick embryos were divided into two groups. One group was grown in a tissue culture dish for 10 days. The other group was placed in a perfusion system termed a joint-simulating device (JSD). After a period of 10 days, histology and immunohistochemistry were performed on five epiphyses from each group. Histologically, epiphyses grown in the device coalesced into a homogenous three-dimensional mass. The bridging tissue between individual epiphyses was highly cellular (PCNA staining positive) and was composed of mesenchymal stem cells as shown by expression of FGF receptor 3. No such tissue formed between epiphyses in the tissue culture dish and the epiphyseal cores were shown to be necrotic. The rest of the epiphyses were evaluated for radioactive sulfate incorporation into glycosaminoglycans (GAGs). A tenfold increase in sulfate incorporation occurred in epiphyses grown within the JSD as compared to the traditional culture method. In conclusion, embryonic epiphyses could be a suitable source for the ex-vivo growth of tissue-engineered cartilage constructs that might later be used as an in-vivo cartilage implant. The joint simulating device effectively maintains cartilage viability and bioactivity for as long as 10 days.

Animals↗

Facet orientation in the thoracolumbar spine: three-dimensional anatomic and biomechanical analysis.

STUDY DESIGN: Thoracolumbar facet orientations were measured and analyzed. OBJECTIVES: To establish a comprehensive database for facet orientation in the thoracolumbar vertebrae and to determine the normal human condition. SUMMARY OF BACKGROUND DATA: Most studies on facet orientation have based their conclusions on two-dimensional measurements, in small samples or isolated vertebrae. The amount of normal asymmetry in facet orientation is poorly addressed. METHODS: Transverse and longitudinal facet angles were measured directly from 240 human vertebral columns (males/females, blacks/whites). The specimens' osteologic material is part of the Hamann-Todd Osteological Collection housed at the Cleveland Museum of Natural History (Cleveland, OH). A total of 4,080 vertebrae (T1-L5) from the vertebral columns of individuals 20 to 80 years of age were measured, using a Microscribe three-dimensional apparatus (Immersion Co., San Jose, CA). Data were recorded directly on computer software. Statistical analysis included paired t tests and analysis of variance. RESULTS.: Facet orientation is independent of gender, age, and ethnic group. Asymmetry in facet orientation is found in the thorax. All thoracolumbar facets are positioned in an oblique plane. In the transverse plane, all facets from T1 to T11 are positioned with an anterior inclination of approximately 25 degrees to 30 degrees from the frontal plane. The facets of T12-L2 are oriented closer to the midsagittal plane of the vertebral body (mean range, 25.89 degrees-33.87 degrees), while the facets of L3-L5 are oriented away from that plane (mean range, 40.40 degrees-56.30 degrees). Facet transverse orientation at the thoracolumbar junction is highly variable (approximately 80% with approximately 101 degrees and approximately 20% with 35 degrees). All facets are oriented more vertically from T1 (approximately 150 degrees) to L5 (approximately 170 degrees). The facet sagittal orientations of the lumbar zygoapophyseal joints are not equivalent. CONCLUSIONS.: Asymmetry in facet orientation is a normal characteristic in the thorax.

Adult↗

CMF608-a novel mechanical strain-induced bone-specific protein expressed in early osteochondroprogenitor cells.

Microarray gene expression analysis was utilized to identify genes upregulated in primary rat calvaria cultures in response to mechanical force. One of the identified genes designated CMF608 appeared to be novel. The corresponding full-length cDNA was cloned and characterized in more details. It encodes a putative 2597 amino acid protein containing N-terminal signal peptide, six leucine-rich repeats (LRRs), and 12 immunoglobulin-like repeats, 10 of which are clustered within the C-terminus. Expression of CMF608 is bone-specific and the main type of CMF608-positive cells is mesenchymal osteochondroprogenitors with fibroblast-like morphology. These cells reside in the perichondral fibrous ring of La Croix, periosteum, endosteum of normal bone as well as in the activated periosteum and early fibrous callus generated postfracture. Expression of CMF608 is notably absent from the regions of endochondral ossification. Mature bone cell types do not produce CMF608 with the exception of chondrocytes of the tangential layer of the articular cartilage, which are thought to be under constant mechanical loading. Ectopic expression of CMF608 in HEK293T cells shows that the protein is subjected to post-translational processing and its N-terminal approximately 90 kDa polypeptide can be found in the conditioned medium. Ectopic expression of either the full-length cDNA of CMF608 or of its N-terminal region in CMF608-negative ROS17/2.8 rat osteosarcoma cells results in transfected clones displaying increased proliferation rate and the characteristics of less-differentiated osteoblasts compared to the control cells. Our data indicate that CMF608 is a unique marker of early osteochondroprogenitor cells. We propose that it could be functionally involved in maintenance of the osteochondroprogenitor cells pool and its down-regulation precedes terminal differentiation.

Amino Acid Sequence↗

Restoration of arthritic cartilage defects using autologous chondrocytes transplantation is superior to cartilage-paste graft in rabbits.

This study compared the articular cartilage repair potential of cultured chondrocytes transplantation with bone-cartilage paste-graft in the resurfacing of full-thickness defects without breaching of the subchondral bone plate in rabbit knees. A 5 x 5-mm articular cartilage defect was created in the patellar groove of the femur. Three months following creation, the defect was filled with cultured autologous chondrocytes (group 1) or bone-cartilage paste (group 2). A control group of untreated defects was followed for 1 year. The reparative tissue was analyzed macroscopically, histologically, and by immunohistochemistry 3-12 months post-transplantation. The surfaces of the reparative tissue in group 1 were smooth, and the defects were filled with reparative tissue that resembled hyaline cartilage. The composition of the repair tissue more closely resembled cartilage, as demonstrated by cartilage-specific stains. In contrast, the reparative tissue in group 2 was fibrous and exhibited markers of mesenchymal stem cells and bone formation. Transplantation of cultured chondrocytes into a full-thickness defect in the rabbit generates a biologic substitute tissue that resembles native articular cartilage with living cells capable of synthesizing the surrounding cartilage matrix. In contrast, analysis of the healing response to the paste-graft technique failed to show cartilage-like characteristics. This information may be clinically applicable to direct the use of these treatments in chondral injuries.

Animals↗

Cryotherapy of musculoskeletal tumors--from basic science to clinical results.

Combined modality treatment of musculoskeletal tumors led to improved patient survival. As survival improves, more consideration is given to the functional outcome of treatment, and interest is focused on the development of less mutilating and extensive surgery. One modality that can reduce patient disability significantly is cryosurgery, as it allows minimally invasive surgery based on marginal resection and tumor interface sterilization instead of wide resection of certain neoplasms. Classical cryosurgery as developed by Marcove involves pouring of liquid nitrogen into the tumor bed. This approach revolutionized the treatment of some tumors such as giant cell tumor of bone, allowing intra-lesional resection to substitute the wide-resection method used up to that time. However, complications of this method of treatment are common, including nitrogen emboli, fractures of the bone due to extensive necrosis and damage to neurovascular elements. A recent development in the field of cryosurgery has been the argon-based system allowing controlled formation of an ice-ball surrounding a metallic probe. The system is computer controlled and allows precise evaluation of the tumor bed interface as well as surrounding structures that need to be protected. Prior to application of this method in humans it is important to ensure that interface sterilization is indeed achieved using cryosurgery. To evaluate this question, a Swarm rat chondrosarcoma was used. Cell viability was assessed following ice-ball formation. Histological evaluation indicated that cell death occurs up to 5 millimeters from the ice-ball if temperatures of -40 degrees Celsius at the metallic probe are achieved. A further evaluation was performed on samples obtained from patients during surgery. A minimum of two freezing cycles was shown to be necessary to achieve tissue viability similar to that of boiled tissue. Twenty-seven patients were operated to date using an argon-based cryosurgery system. The patients included 7 cases of grade I chondrosarcoma, 5 cases of giant cell tumor of bone, 14 cases of a metastatic lytic bone lesion and a single case of osseous-fibrous dysplasia. None of the patients suffered nerve injury during the operation. After a minimal follow-up period of 2 years only two of the surviving patients had a recurrence (a giant cell tumor of the proximal fibula, and the patient with the osseous-fibrous dysplasia whose tumor recurred as a frankly malignant adamantimoma). There were no pathological fractures. This method appears practical and allows close monitoring of the surrounding tissue to reduce the chances of recurrence.

Animals↗

The short-lived exostosis induced surgically versus the lasting genetic hereditary multiple exostoses.

Hereditary osteochondromas are often caused by mutation in the EXT1 gene. The lesions are typified by formation of a "pseudo" growth plate like lesion growing at 60 degrees to the normal growth direction of the bone. Such lesions can be mimicked surgically by reverting the position--the polarity of the zone of LaCroix. The current study attempts to compare the pathology between EXT1 gene expression in humans and surgically created osteochondroma pathology in a rat model. Tissues of human bunion, human embryonal tissue, and human adult cartilage as well as normal rat epiphyses served as controls. Rats were operated on and a 60 degree span of the ring of LaCroix was inverted as described by Delgado (Delgado, E., Rodriguez, J. I., Serada, A., Tellez, M., and Pariagoa, R.. Clin. Orthop. 201, 251-258 (1985)). The surgically created osteochondromas were assessed by histology, histochemistry, and immunohistochemistry. The findings show that the surgically created lesions contain only a small amount of FGF receptor 3 (FGFR3) expressed on mesenchymal stem cells located in the perichondrium, as compared to the cell population carrying FGFR3 in the contralateral limb. Indian hedgehog and Bcl2 are downregulated, while BMP-2 is overexpressed in the operated limb, compared to the LaCroix ring of the contralaetral limb. The shortage, as well as the disturbed migration routes of the residual mesenchymal stem cells in surgically created osteochondromas leads eventually to resorption of the pathological elements. In search of additional markers characterizing such pathological structures composed of mesenchymal stem cells and cartilaginous and bony cells, EXT1 gene was found to be expressed in the surgically created osteochondromas, like in normal growth plates. Nitric oxide synthase was also expressed like in adult cartilage, though tumor necrosis factor alpha typifying Bunion formation was absent. In summary, surgically created osteochondromas lack the massive and continuous population of mesenchymal stem cells with Bcl2 expression. However, the small residual mesenchymal cell population gives rise to short-lived EXT1-expressing cells that disappear eventually due to spontaneous resorption.

Animals↗

Symptomatic transient patellar ischemia following total knee replacement as detected by scintigraphy. A prospective, randomized, double-blind study comparing the mid-vastus to the medial para-patellar approach.

The most advantageous surgical approach for total knee arthroplasty is not defined. The mid-vastus approach has been suggested to improve patient rehabilitation and prevent patellar devascularization. The following study assessed the changes in patellar vascularity as determined by bone scanning following total knee arthroplasty without lateral release or patellar replacement. A total of 30 patients were randomly allocated to either undergo a medial para-patellar approach or a midvastus approach. All patients underwent a pre-operative bone scan and another scan was performed 5-7 days later. The bone scans were compared to assess the intensity of patellar uptake. In 4/30 (13.5%) of subjects, evenly distributed among the two study groups, patellar ischemia was demonstrated by decreased radioisotope uptake. These subjects underwent a third bone scan 1 month later. The latter scan demonstrated similar uptake to the pre-operative scan. These patients continue to suffer from anterior knee pain and show a positive patellar grinding test, which were not found in other patients. The current study appears to indicate that transient patellar ischemia is relatively common following total knee arthroplasty, even when no lateral release is performed. The surgical approach does not seem to affect the frequency of patellar ischemia. This phenomenon might be related to clinical symptoms of anterior knee pain.

Aged↗

Improved regional left ventricular function after successful satellite cell grafting in rabbits with myocardial infarction.

OBJECTIVE: To evaluate whether satellite cells injected into infarct areas in rabbits remain viable during 6 weeks follow-up and can improve cardiac function as assessed by echocardiography. METHODS: Myocardial infarction was induced in 16 New Zealand white rabbits, by ligation of the marginalis sinistra artery. Tissue from gluteus muscle biopsies was dissected into small pieces and cultured. Within 2-3 weeks the cells were expanded by 2-3 orders of magnitude and were fluorescent labeled. Single cell pellets for resuspension at >10(6)/1 ml were directly injected into the infarct areas in 8 rabbits. In 8 additional rabbits, 1 ml saline was injected (control). Regional left ventricular function was assessed weekly by 2-D echocardiography until animals were sacrificed. Analysis was performed blind and independently by two experienced echocardiographers, based on the American Society of Echocardiography scheme. RESULTS AND DISCUSSION: Six treated and five control rabbits completed the study. One week after the artery occlusion, left ventricular function scoring did not differ between groups, mean 8.7+/-1.6 vs 8.3+/-1.9 (P=0.74). At 6 weeks post-injection, echocardiographic score was significantly better in the treated group, mean 2.6+/-0.9 vs 6.9+/-2.1 (P=0.002). The treated group showed significant gradual segmental improvement between the first week up to week 6. After sacrifice, macro and microscopic transmural areas showed typical changes of myocardial infarction. Histochemical staining identified viable grafted cells in high density 6 weeks post-transplantation in all grafted hearts. CONCLUSION: Autologous satellite cells (skeletal myofiber), can be successfully grafted into rabbit hearts following myocardial infarction and may induce improved regional left ventricular function.

Animals↗

Articular cartilage reconstruction using xenogeneic epiphyses slices.

Reconstruction of articular cartilage defects using adult osteochondral allografts is an established clinical procedure, whose principal drawback is lack of lateral integration of the grafts to the surrounding tissue. Autologous chondrocytes transplantation is a sophisticated technique requiring cell culture and a staged operation. Its main draw back is the lack of mechanical strength early on. This study was conducted in order to evaluate the possibility of using embryonal epiphyses as a cartilage reconstruction tissue. A xenogeneic human to rabbit sub-acute osteochondral defect model was designed to evaluate the possibility of allogeneic implantation in humans. The following procedures were perfomed (n = 5): transplantation of 1. live epiphyses 2. live epiphyses with autogeneic periosteum 3. de-vitalized epiphyses and 4. devitalized epiphyses with autogeneic articular chondrocytes. A fifth control group did not receive any implant. Animals in groups 1 and 2 had a viable reconstruction of the articular surface with little evidence of rejection and without pannus formation. Animals in groups 3 and 4 became severely arthritic and the graft was resorbed. Nitric oxide synthase accumulation was reduced in group 1 and 2 as compared to groups 3, 4, and 5, indicating a joint preserving function of the epiphyseal grafts. Epiphyseal grafts appear to be a feasible procedure for reconstruction of articular cartilage defects even in a xenogeneic model.

Journal Article↗

[Vertebroplasty as a treatment for painful pathological fractures of the vertebral column].

Vertebral fracture due to a metabolic bone disease or a neoplastic disease is a common and debilitating condition occurring mostly due to osteoporosis or metastatic bone disease. Some of the patients suffering from such fractures continue to complain of back pain and deformity despite optimal medical therapy. Vertebroplasty, i.e. transcutaneous injection of bone cement into the vertebral body can serve as an internal fixation device and allows restoration of mechanical strength and partial restoration of the vertebral height. During the year 2000, 17 vertebrae in 12 patients were injected. These were either lumbar or thoracic vertebrae. All patients reported a decrease in pain and improved ambulation capacity. Two minor complications were encountered including headache lasting for 72 hours prior to spontaneously resolving. This possibly indicates a trans-arachnoidal approach. The other complication encountered was cement leak below the posterior longitudinal ligament. The patient reported pain amelioration. No emergency surgical interventions were necessary to date.

Aged↗

Shoulder girdle neoplasms mimicking frozen shoulder syndrome.

Shoulder pain and immobility comprise a multifactorial disorder apparently affected by pain inhibiting joint motion. As the syndrome is very common, many patients do not undergo detailed imaging studies before treatment. This study compared a series of 7 patients in whom a neoplasm was the underlying cause for the stiff shoulder with a series of 50 patients with primary or secondary frozen shoulder. In addition to a detailed history being taken, the Disabilities of the Arm, Shoulder, and Hand (DASH) upper limb outcomes data collection questionnaire was completed and physical examination, radiography, ultrasonography, and bone scanning were performed in all cases. In the cases of tumor, the presenting symptom was a stiff shoulder without radiographic abnormality in 7 of 67 patients with shoulder girdle neoplasms who were seen at our musculoskeletal oncology clinic. The tumors included osteoid osteoma, osteoblastoma, metastatic carcinoma, chondrosarcoma, periosteal lipoma, and acute lymphoblastic lymphoma. The diagnosis was established in all cases by an area of focal isotope uptake demonstrated by a routine technetium 99 methylene diphosphonate bone scan. In a single case of metastatic colon carcinoma, the diagnosis could only be established by magnetic resonance imaging, as the radiographs were normal and the bone scan demonstrated diffuse uptake over the proximal humerus. The patients whose frozen shoulder was caused by an underlying tumor were significantly younger and had a lower fatigue/energy dimension score on the RAND Short Form-36 health survey. The most useful diagnostic test appears to be a discrete area of bony tenderness, present in 7 of 7 patients with tumor and in only 5 of 50 patients in the control group. Although an underlying tumor is a rare cause of frozen shoulder syndrome, the potential grave consequences of misdiagnosis and the possibility of performing an unnecessary and ineffective invasive procedure should prompt physicians to increased vigilance. In patients with discrete bony tenderness elicited by light tapping, a bone scan should be ordered and magnetic resonance imaging should be considered.

Adolescent↗