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Biomedical subjects

D Kohn

Publications and source records attributed to D Kohn.

At least 55 records · Page 3Linked to original sources

[In Process Citation]

Calcifying tendinitis of the rotator cuff is a common||| disorder of the shoulder which affects mainly individuals between 30 and 50||| years of age. The etiology is still a matter of speculation. The calcification||| is a reactive process actively mediated by cells in a viable environment. The||| deposit undergoes an evolution (precalcific stage--calcific stage with||| formative phase, resting period and resorption--postcalcific stage), which||| ultimately remodels normal tendon tissue. However, the evolutionary stages of||| the disease do not always follow the typical sequence. A symptomatic deposit||| may persist or postcalcific tendinitis develop. The treatment should be based||| on the knowledge of the natural history of the disease, which shows a strong||| tendency towards self-healing by spontaneous resorption of the deposit. The||| stage of evolution of the disease should be judged, combining pain history,||| morphology of the deposit on plain X-rays, and ultrasound findings. The||| therapeutic approach depends on the evolution of the disease. During the||| resorption phase we favor a conservative approach. For deposits which are not||| under resorption we propose a concept which consists of three steps: a||| conservative approach, extracorporal shock wave therapy (ESWT) or needling, and||| arthroscopic surgery. The efficacy of ESWT and needling has still to be proven.||| Patients with persisting pain after steps 1 and 2 are candidates for surgical||| removal of the deposit. We prefer the arthroscopic approach. In some cases an||| additional arthroscopic subacromial decompression (ASD) is||| indicated.

Journal Article↗

[Tendinosis calcarea of the rotator cuff].

Calcifying tendinitis of the rotator cuff is a common disorder of the shoulder which affects mainly individuals between 30 and 50 years of age. The etiology is still a matter of speculation. The calcification is a reactive process actively mediated by cells in a viable environment. The deposit undergoes an evolution (precalcific stage--calcific stage with formative phase, resting period and resorption--postcalcific stage), which ultimately remodels normal tendon tissue. However, the evolutionary stages of the disease do not always follow the typical sequence. A symptomatic deposit may persist or postcalcific tendinitis develop. The treatment should be based on the knowledge of the natural history of the disease, which shows a strong tendency towards self-healing by spontaneous resorption of the deposit. The stage of evolution of the disease should be judged, combining pain history, morphology of the deposit on plain X-rays, and ultrasound findings. The therapeutic approach depends on the evolution of the disease. During the resorption phase we favor a conservative approach. For deposits which are not under resorption we propose a concept which consists of three steps: a conservative approach, extracorporal shock wave therapy (ESWT) or needling, and arthroscopic surgery. The efficacy of ESWT and needling has still to be proven. Patients with persisting pain after steps 1 and 2 are candidates for surgical removal of the deposit. We prefer the arthroscopic approach. In some cases an additional arthroscopic subacromial decompression (ASD) is indicated.

Adult↗

[Ruptures of the anterior cruciate ligament (ACL) during growth].

Tears of the anterior cruciate ligament (ACL) in skeletally immature patients with open physes are becoming more frequent. The two main variants of this lesion include tibial eminence fractures with an avulsion of the bony avulsions of the ACL on the tibia and midsubstance ligament injuries. The treatment of bony avulsions is generally accepted. In complete midsubstance tears conservative treatment is insufficient, resulting in multiple giving way episodes and meniscal lesions. Controversy exists regarding the surgical treatment of complete midsubstance ruptures. Especially in younger patients with wide open physes, the risk of a growth disturbance due to transphyseal drilling has not been completely evaluated. In patients approaching physeal closure intraarticular ACL replacement using an autogenous bone-patellar tendon-bone graft has been shown to yield good short-term to mid-term results. There is a growing concern regarding the long-term outcome of ACL grafts with higher rerupture rates being suspected in children compared to adults. For these reasons more clinical and experimental data are needed in forthcoming studies.

Adult↗

Genetically corrected autologous stem cells engraft, but host immune responses limit their utility in canine alpha-L-iduronidase deficiency.

Canine alpha-L-iduronidase (alpha-ID) deficiency, a model of the human storage disorder mucopolysaccharidosis type I (MPS I), is an ideal system in which to evaluate the clinical benefit of genetically corrected hematopoietic stem cells. We performed adoptive transfer of genetically corrected autologous hematopoietic cells in dogs with alpha-ID deficiency. Large volume marrow collections were performed on five alpha-ID-deficient dogs. Marrow mononuclear cells in long-term marrow cultures (LTMCs) were exposed on three occasions during 3 weeks of culture to retroviral vectors bearing the normal canine alpha-ID cDNA. Transduced LTMC cells from deficient dogs expressed enzymatically active alpha-ID at 10 to 200 times the levels seen in normal dogs. An average of 32% of LTMC-derived clonogenic hematopoietic cells were provirus positive by polymerase chain reaction and about half of these expressed alpha-ID. Approximately 10(7) autologous gene-modified LTMC cells/kg were infused into nonmyeloablated recipients. Proviral DNA was detected in up to 10% of individual marrow-derived hematopoietic colonies and in 0.01% to 1% of blood and marrow leukocytes at up to 2 to 3 years postinfusion. Despite good evidence for engraftment of provirally marked cells, neither alpha-ID enzyme nor alpha-ID transcripts were detected in any dog. We evaluated immune responses against alpha-ID and transduced cells. Humoral responses to alpha-ID and serum components of the culture media (fetal bovine and horse sera and bovine serum albumin) were identified by enzyme-linked immunosorbent assay. Cellular immune responses to autologous alpha-ID but not neo(r) transduced cells were demonstrated by lymphocyte proliferation assays. To abrogate potential immune phenomena, four affected dogs received posttransplant cyclosporine A. Whereas immune responses were dampened in these dogs, alpha-ID activity remained undetectable. In none of the dogs engrafted with genetically corrected cells was there evidence for clinical improvement. Our data suggest that, whereas the alpha-ID cDNA may be transferred and maintained in approximately 5% of hematopoietic progenitors, the potential of this approach appears limited by the levels of provirally derived enzyme that are expressed in vivo and by the host's response to cultured and transduced hematopoietic cells expressing foreign proteins.

Animals↗

[Arthroscopy for diagnosis and therapy of early osteoarthritis of the hip].

Failure to conservative treatment in patients with less advanced radiographic signs of osteoarthritis of the hip (Danielsson grade 2-5) confronts with the decision of further treatment. Since radiographic imaging has not been proved very useful in demonstrating intraarticular structures and results of hip arthroscopies have been promising, arthroscopies have been performed in 17 hips from November 1997 to September 1998. Arthroscopic findings were exceeding preoperative imaging. In addition to cartilage degeneration, concomitant loose bodies, impinging osteophytes, degeneration of the labrum and synovial disease were found. Removal of loose bodies and osteophytes, partial resection of labral tears and partial synovectomy were performed. 1 month after arthroscopy (n = 15), mean Harris-Hip-Score was increased by 13 points und pain reduced by 39 % on average. 6 months after arthroscopy (n = 9), mean Harris-Hip-Score was increased by 14 points and pain reduced by 32 % on average. In addition to its therapeutic benefit, arthroscopy offers direct visualisation of the hip providing important information for the decision of further treatment.

Arthroscopy↗

[Indication for and performance of articular cartilage drilling using the Pridie method].

Articular cartilage has only a small capacity for regneration. This makes the repair of articular surfaces difficult. In 1959 Pridie described his method of resurfacing osteoarthritic knee joints. This operation is still in widespread use today. Pridie introduced the principle of drilling exposed subchondral bone with the objective of encouraging a fibro-cartilaginous repair. The newly formed fibrocartilaginous layer that develops over the lesion in osteoarthritis may be enough to decrease patients symptoms. Bone drilling into the subchondral layer is also effective in promoting healing of osteochondrosis dissecans. The choice of the treatment should be based on factors such as age of the patient, serverity of symptoms, activity level and functional demands on the joint, site and stage of the lesion. The drilling operation remains useful in osteoathritis and osteochondrosis dissecans.

Bone Regeneration↗

Primary stability of different implants used in conjunction with high tibial osteotomy.

High tibial osteotomy in the varus knee has been successfully performed for a long time. Several newer operation techniques have been established in recent years. We tested the primary stability of several of these techniques in vitro. Ten human cadaveric fresh-frozen specimens were used that had a mean age of 54 years (range 29-72 years) and a weight of 55-85 kg. All specimens were harvested, frozen, and subsequently thawed under the same conditions before testing. The following implants were tested: one-third tubular plate with a cortical screw (AO, Synthes), blade plate with screws (Giebel's plate, Link), bone staples (osteotomy staples, Krackow staples, Smith & Nephew) and an external fixator (Orthofix). The specimens were mounted in metal cylinders and then loaded in two different setups: transverse forces were applied to the osteotomy site by hanging weights parallel to the osteotomy plane in a static-loading frame, and axial forces were applied by a materials testing machine (Zwick). Displacement was recorded using a linear variable displacement transducer (LVDT). The highest stability was achieved by the external fixator and the bone staples. Giebel's blade plate and the one-third tubular plate were less stable. Retention of an intact medial cortex was a decisive factor in obtaining primary stability. We found that the primary stability of the tested devices was generally comparable as long as they were correctly implanted. It was also noted that lateral spacing of the osteotomized bone should not exceed 3 mm. If the medial cortex is transected intraoperatively in lateral osteosynthesis, an additional medial implant is necessary to ensure sufficient primary stability. For practical reasons it was necessary to neglect the contribution of the soft tissues around the knee, although all implants were tested under the same conditions. Care should thus be taken when interpreting the results of this study in a clinical setting.

Adult↗

Popliteal cyst accompanied by an intra-articular cartilage lesion in a child.

The case of an 11-year-old girl presenting with a symptomatic popliteal cyst is described. There was no previous knee trauma nor could any inflammation be found. On MRI a concomitant retropatellar cartilage lesion had been detected preoperatively and was confirmed and treated by arthroscopy. The prevalence and treatment of popliteal cysts in children are discussed. Whereas in adults popliteal cysts are generally accompanied by intra-articular lesions, the presence of a concomitant intraarticular lesion in children is an extremely rare finding. We conclude that intraarticular lesions in the presence of popliteal cysts might have been underestimated as most of the studies regarding popliteal cysts in children were undertaken before the advent of arthroscopy, ultrasound, or MRI.

Child↗

A comparative study of two cerclage systems.

Intraoperative femoral fracture is a well recognized technical complication of cementless total hip arthroplasty (THA). The aim of this study was to establish an in vitro model for initiation of fractures of the femur in cementless THA and to assess the effect of fracture fixation by cerclage wiring. An in vitro comparison of two methods of cerclage fixation was performed using steel wire (Protasul) versus multifilament Vitallium alloy cable. Ten fresh human femur specimens were studied. Longitudinal fractures were created on a material testing machine. The force to create a longitudinal fracture in the femur was 1915 N to 9288 N (median 6531 N). This force corresponds 3 to 15 times (median 11 times) the body weight. The femoral cortex was fractured in 5 cases ventrally, in 6 cases medially and in 1 case laterally. After monofile cerclage wire application, the force required to press the prosthesis 5 mm deeper into the medullary canal was 0.3-2.7 times body weight. After Vitallium alloy cable application in other specimens, the force was 1.3-2.7 times body weight. The difference was not statistically significant. After monofile cerclage wire application, a force of 1.8-8.1 times body weight was necessary to press the prosthesis 30 mm deeper into the medullary canal. After polyfile Vitallium alloy cable application in other specimens, the force was 7.7-12 times body weight. The difference was statistically significant (U-test, alpha < 0.025).

Adult↗

Prevalence of popliteal cysts in children. A sonographic study and review of the literature.

Popliteal cysts in children differ from those in adults. They are considered to be less frequent and usually appear in the absence of intra-articular lesions. However, their prevalence in asymptomatic children is unknown. We present a prospective epidemiological study of 168 asymptomatic children under 15 years of age hospitalised for various pathologies. Children with knee problems and rheumatic diseases were excluded from the study. The children were examined ultrasonographically with a 7.5 MHz linear scanner. A popliteal cyst could be identified in 4 patients. The prevalence of asymptomatic popliteal cysts was thus 2.4%. For 2 of these patients, we obtained magnetic resonance image of the knee which showed no concommitant intra-articular pathology.

Adolescent↗

Immune response to green fluorescent protein: implications for gene therapy.

Green fluorescent protein (GFP) is a widely used intracellular reporter molecule to assess gene transfer and expression. A potential use for GFP is as a co-expressed marker, to select and enrich gene-modified cells by flow cytometry. Processed peptides derived from GFP and presented by the major histocompatibility complex on the cell surface could potentially induce T cell immune responses against GFP+ cells. Thus, clinical application of GFP is premature, since in vivo studies on its immunogenicity are lacking. Therefore, we investigated immune responses against EGFP (enhanced-GFP) in two transplantable murine models: the BALB/c (H-2d) BM185 pre-B leukemia and the C57BL/6 (H-2b) EL-4 T cell lymphoma. BM185 and EL-4 cell lines modified to express high levels of EGFP showed drastic reduction of disease development when transplanted into immunocompetent mice. BM185/ EGFP did lead to rapid development of disease in immunodeficient Nu/Nu mice. Mice surviving BM185/EGFP leukemia challenge developed high cytotoxic T lymphocyte (CTL) responses against EGFP-expressing cells. Furthermore, immune stimulation against BM185/EGFP cells could also be induced by immunization with EGFP+ transduced dendritic cells. The effects of the co-expression of EGFP and immunomodulators (CD80 plus GM-CSF) were also investigated as an irradiated leukemia vaccine. EGFP co-expression by the vaccine did not interfere with the development of CTLs against the parental leukemia or with the anti-leukemia response in vivo. These results indicate that the immune response against EGFP may interfere with its applicability in gene insertion/replacement strategies but could potentially be employed for leukemia cell vaccines.

Animals↗

Meniscal substitutes--animal experience.

Animal studies have shown that meniscus allografts and tendon autografts generally heal to the capsule, are revascularized and repopulated with host cells. In animals, neither meniscal allografts nor tendon or fat autografts gain the properties of a normal meniscus. Meniscus allografts and tendon autografts are promising as both seem to offer some protection to the cartilage of the tibial plateau. There is no evidence that meniscal transplantation can prevent cartilage degenerative changes, and the long-term effect of meniscal transplantation on articular cartilage remains unknown. Whether cellular repopulation of the meniscal allograft is sufficient to restore its biomechanical properties is unknown. Collagen scaffolds and tissue engineered grafts are still under investigation, showing promising results especially for the former. Viable meniscal allografts should be implanted within 1 to 2 weeks after harvesting, as the production of proteoglycans decreases after 2 weeks.

Animals↗

Meniscal substitutes--human experience.

A number of clinical series have described the effect of meniscus allograft replacement in humans. The general indication has been disabling pain following loss of a meniscus in a skeletally mature individual. Overall, healing of the graft to the capsule occurs in up to 80% of all transplants. Revascularization and cell repopulation is found in all grafts but is highly variable. The risk for graft failure seems to be greater with irradiated grafts and in patients with grade III or IV osteoarthritic changes. In most series, patients experienced a decrease in pain and an increase in activity level postoperatively. In many series, concominant surgery (cruciate ligament reconstruction or osteotomy) had been performed. Meniscus replacement with frozen or cryopreserved allografts seems to give the most promising short-term results in patients with post-meniscectomy pain. Controlled, randomized prospective studies are needed to confirm a long-term benefit and better define transplantation indications. Viable meniscus allografts seem to survive transplantation, as donor cells were found in the graft after 2 years. Clinically, pain was reduced and activity increased following transplantation, but after 4 years some of these gains were lost. There was no correlation between postoperative findings on MRI and clinical outcome. Meniscal replacement with a quadriceps tendon autograft in humans resulted in pain reduction, but at second-look arthroscopy, only 2 of 9 tendon autografts looked like a meniscus. Six were in position but still looked like tendons. Total medial meniscus replacement by quadriceps tendon autrograft is still an experimental procedure. There is no proof at present that meniscal substitutes (meniscus allografts or tendon autografts) in humans can protect the hyaline cartilage of the knee from the degeneration, following loss of a meniscus. There is some evidence in animal experiments that under circumstances not yet exactly known, a meniscus substitute can have a protective effect on articular cartilage. Three factors have been identified that prevent proper meniscal function: poor fixation of the meniscal horns, no contact of the graft with the articulating surfaces under load and incorrect positioning of the horns. Meniscal allograft transplantation sensitizes humoral and cell mediated immune systems. Bone plugs attached to meniscal allograft tissue may increase cell surface antigenicity. Deep freezing and especially freeze drying of meniscal tissue decreases host immunogenicity. Cryopreservation maintains the content of donor HLA encoded antigens and is likely more sensitizing to the host. The clinical importance of immune responses to meniscal allografts is not known, but it has not been shown to result in graft failure or rejection. Prospective studies are needed.

Antibody Formation↗

Harvest and conservation of meniscal allografts.

Meniscal allografts can be harvested and preserved in different ways. A technique for harvesting and conserving viable allografts is described. The meniscus should be harvested within 12 h after the start of ischaemia. The ideal time for implantation of the viable graft is 10 to 14 days after harvest, in which time a recipient should be identified. Frozen grafts are avital. Cryopreserved grafts are not avital, as 10-30% of the fibrochondrocytes are preserved. Frozen and cryopreserved grafts can be stored for a long time and if a graft bank is established, grafts are always readily available. There is no proven advantage of one graft type over others.

Cryopreservation↗