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Biomedical subjects

M Siemionow

Publications and source records attributed to M Siemionow.

At least 19 recordsLinked to original sources
PubMed2006

Trafficking of donor-derived bone marrow correlates with chimerism and extension of composite allograft survival across MHC barrier.

We proposed to evaluate differences between recipient's immune response to vascularized skin and combined vascularized skin/bone allografts, under a 7-day alphabeta-TCR plus cyclosporine (CsA) treatment protocol. Thirty-six transplantations were performed in six groups: group I (isograft control-vascularized skin graft; n=6); group II (isograft control-combined vascularized skin/bone graft; n=6); group III (allograft rejection control group-vascularized skin graft; n=6); group IV (allograft rejection control-combined vascularized skin/bone graft; n=6); group V (allograft treatment-vascularized skin graft; n=6); and group VI (allograft treatment-combined vascularized skin/bone graft; n=6). Isograft transplantations were performed between Lewis rats and allografts were transplanted across the MHC barrier from Brown Norway to Lewis rats. In the allograft treatment group, a combined alphabeta-TCR+CsA protocol was applied for 7 days. All groups were compared clinically, immunologically and histologically. Statistical significance was determined with two-tailed Student's t test. Indefinite graft survival was achieved in the isograft control group (>300 days). Allograft rejection controls rejected within 5 to 9 days posttransplant; chimerism levels were undetectable (<.5%). Allografts under the alphabeta-TCR+CsA protocol had significantly extended survival when skin was combined with bone (61-125 days) compared to vascularized skin allografts (43-61 days). Lymphoid macrochimerism was significantly higher in group VI than group V. Histology confirmed skin and bone viability. Combined vascularized skin/bone allografts had higher and sustained levels of donor-specific chimerism and extended allograft survival.

Animals↗
PubMed2006

Laryngeal transplantation in 2005: a review.

There is no good surgical, medical or prosthetic solution to the problems faced by those with a larynx whose function is irreversibly damaged by tumor or trauma. Over the past 10 years, the pace of research designed to establish laryngeal transplantation as a therapeutic option for these persons has increased steadily. The biggest milestone in this field was the world's first true laryngeal transplant performed in Cleveland, Ohio in 1998. The recipient's graft continues to function well, in many respects, even after 7 years. However, it has also highlighted the remaining barriers to full-scale clinical trials. Stimulated by these observations, several groups have accumulated data which point to answers to some of the outstanding questions surrounding functional reinnervation and immunomodulation. This review seeks to outline the progress achieved in this field by 2005 and to point the way forward for laryngeal transplantation research in the 21st century.

Animals↗
PubMed2005

The endoscopic management of cubital tunnel syndrome.

The overall success rate of surgical interventions for cubital tunnel syndrome is reported to be within 80% to 90% (Szabo, 1999). The discussion, however, whether to perform in situ nerve decompression or anterior transposition continues. In this paper, we present the results of our endoscopic approach to in situ cubital tunnel release, its rationale, clinical and anatomical indications and a detailed description of the technique.

Adult↗
PubMed2005

A new method of bone marrow transplantation leads to extension of skin allograft survival.

Tolerance induction through allogeneic bone marrow transplantation is an alternative method to chronic immunosuppression in maintaining long-term allograft survival. In this article, we introduce a new method of bone marrow allotransplantation, which preserves its natural microenvironment and does not require marrow processing or recipient conditioning. A total of 43 skin graft transplantations were performed in nine experimental groups between isogeneic [Lewis to Lewis (LEW, RT1(1))] and allogeneic [Lewis x Brown Norway (LBN --> F1, RT1(1+n)) to Lewis] rats under 35-day protocol of alphabeta T-cell receptor (TCR) monoclonal antibody (mAb) and cyclosporine (CsA) protocol. Monotherapies combined with "crude" bone marrow transplantation resulted in extended survival up to 21 days under CsA and up to 10 days under alphabeta-TCR mAb protocol. The use of combined protocol of alphabeta-TCRmAb/CsA with crude bone marrow transplantation resulted in the extension of skin allograft survival up to 65 days (P < .05). This new simple method of "crude" bone marrow allotransplantation without recipient conditioning is a promising, minimally invasive technique with a potential for direct clinical application.

Animals↗
PubMed2005

Intraosseus transplantation of donor-derived hematopoietic stem and progenitor cells induces donor-specific chimerism and extends composite tissue allograft survival.

We investigated the effect of the intraosseous allotransplantation of the donor-derived hematopoietic stem cells (HSC) CD90+ on chimerism induction and survival of rat hind limb transplants. Eighteen rat hind limb transplantations were performed between Lewis-Brown-Norway and Lewis rats in three groups. Isograft and allograft rejection controls received no treatment. In the experimental group, 0.8 to 1.2 x 10(6) of separated and purified CD90+ HSC cells were transplanted intramedullary into the bone marrow cavity of the recipient's tibia during opposite hind limb transplantation, without immunosuppressive therapy. Transplants from isograft group survived indefinitely. Allograft controls rejected transplants on day 7 posttransplant. The injection of separated and purified CD90+ cells of the donor origin extended survival of the transplanted limbs up to 15 days in group III. We introduced a novel method of transplantation of the CD90+ cells of the donor origin into the recipient's bone marrow cavity. This technique resulted in extended allograft survival, without immunosuppressive therapy.

Animals↗
PubMed2005

Until they have faces: the ethics of facial allograft transplantation.

The ethical discussion of facial allograft transplantation (FAT) for severe facial deformity, popularly known as facial transplantation, has been one sided and sensationalistic. It is based on film and fiction rather than science and clinical experience. Based on our experience in developing the first IRB approved protocol for FAT, we critically discuss the problems with this discussion, which overlooks the plight of individuals with severe facial deformities. We discuss why FAT for facial deformity is ethically and surgically justified despite its negative portrayal in the media.

Attitude to Health↗
PubMed2001

Computer-guided microsurgery: surgical evaluation of a telerobotic arm.

A new telerobotic arm was evaluated in different microsurgical procedures. The system consisted of a robotic arm bearing a microsurgical forceps controlled by a joystick-like master unit operated by the surgeon's hand. The robotic arm functioned as an operating as well as assisting instrument. Advantages of the system were its precise functioning, which was especially important when tissue or instruments had to be held for a longer period of time, as well as its ability to replace an assisting person to some extent. Deficiencies of the system were its 10-min startup, the spatial conflict with in the operative field, and the poor rotation of the robotic tip. In some procedures, the telerobotic arm could replace the standard microsurgical instrument guided by the surgeon's second hand; in other maneuvers it could function as the surgeon's third hand with precision and void of tremor.

Anastomosis, Surgical↗
PubMed2001

Combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibody therapy prolongs allograft survival in rat hind-limb transplants.

Immunosuppressive effects of monoclonal antibodies against adhesion molecules were validated in solid organ transplants. There have been only a few reports on the effect of these antibodies on limb transplantation. In this study, the authors investigated the effects of anti-ICAM-1 and anti-LFA-1 therapy in the rat hind-limb-cremaster transplantation model. Twenty transplantations were performed across a major histocompatibility barrier between Lewis Brown Norway (LBN, RT-1(l+n)) and Lewis (LEW, RT-1(l)) rats in four experimental groups of five animals each. Group 1 animals received only vehicle solution; Groups 2 and 3 received monoclonal antibodies against ICAM-1 and LFA-1, respectively; Group 4 received a combination dose. Treatments were continued for 7 days. Clinical signs of rejection were noted daily, and correlated with in vivo microcirculatory measurements. The activation of adhering leukocytes was significantly lower in rats treated with anti-ICAM-1, anti-LFA-1, and combination than in controls (p < 0.05). Transmigrating leukocytes were also reduced in antibody-treated groups, when compared to the control group (p < 0.05). The mean number of rolling lymphocytes was significantly reduced only in the combination group (p < 0.05). Endothelial edema index, a measure of endothelial swelling, was lowest in the combination group (p < 0.05). The first clinical signs of rejection were noted between the 5(th) and 9(th) days in the control group, on the 9(th) day in the anti-ICAM-1 or anti-LFA-1 groups, and on the 13(th) day with combination therapy. Monoclonal antibodies against LFA-1 or ICAM-1 alone inhibit the activation of leukocytes at the microcirculatory level but do not prolong graft survival. However, the combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies significantly prolonged allograft survival in this composite tissue transplantation model.

Analysis of Variance↗
PubMed2001

Neurogenic perspective on vascular endothelial growth factor: review of the literature.

Among a variety of approaches used to stimulate nerve regeneration in experimental settings, is the use of a class of proteins designated as nerve growth factors and various other growth factors. Of these, vascular endothelial growth factor (VEGF), has been demonstrated to possess a potential to stimulate nerve regeneration in addition to its angiogenic properties. A number of studies have investigated the role of VEGF in nerve regeneration, demonstrating that it has both neurogenic and mitogenic activity on cells in the peripheral nervous system. It is therefore likely that VEGF is a molecule of major significance for nerve homeostasis, especially during development, and possibly after nerve injury. This paper reviews the mechanisms of VEGF signal transduction in neurogenesis, and focuses on recent studies that have considerably widened the understanding of the way in which VEGF affects peripheral nerve regeneration. By emphasizing the possible therapeutic implication of VEGF in nerve pathology, the authors would like to introduce a new research approach to study the role of VEGF in the nervous system. They believe that in the future, the factor might become a powerful tool in enhancing nerve regeneration in clinical practice.

Animals↗
PubMed2000

Cranial defect repair using e-PTFE: part I. Evaluation of bone stiffness.

Autologous bone grafts are the preferred material for craniofacial reconstruction, but such procedures lead to increased operative time and bleeding, donor site morbidity, and graft resorption. The efficacy of expanded-polytetrafluoroethylene (e-PTFE) sheets to increase bone regeneration and remodeling in cranial defects using a rabbit model was evaluated by mechanical testing. New Zealand white rabbits were divided into 3 groups and sacrificed 6 months after surgery. In the Split Table group, (n = 16), a bilateral bone defect was created on the outer table of the parietal bones. In the Full Table group, (n = 16), a bilateral defect was created through both the inner and outer table of the cranium. The control group, (n = 10) was subjected to a sham operation. Indentation testing was performed to determine the stiffness of newly formed bone in and around the defect. Near the center of the defect, Split Table defects repaired with e-PTFE resulted in significantly stiffer bone than regenerated control bone. The Full Table defects repaired with e-PTFE also resulted in bone significantly stiffer than control regenerated bone around the central region of the defect. The data supports the hypothesis that e-PTFE improves the repair of cranial defects in a rabbit model. It is surmised that the porosity of the e-PTFE provides a stable scaffold for migration of tissue regenerating cells, which may be preferentially localized near the cranial suture lines. This porosity may also provide a barrier to fibrous tissue regenerating cells.

Animals↗
PubMed2000

Assessment of muscle flap sensibility by evoked potentials in the rat.

This study investigated whether the sensory-to-motor reinervation of the muscle flap provides a better sensory recovery of an overlying skin graft. Fifty-four animals were studied in three groups of 18 rats each: group I (control): 1 cm of the gastrocnemius muscle motor nerve was excised and no repair was performed; group II (motor-to-motor repair): the motor nerve of the gastrocnemius flap was transected and repaired; group III (sensory-to-motor repair): the motor nerve of the gastrocnemius muscle and sural nerve were transected and their distal and proximal ends, respectively, were repaired. At follow-up periods of 6, 12, and 24 weeks, evaluation of hair growth, muscle atrophy, and sensory evoked potentials was performed. Somatosensory evoked potentials (SSEP) at 6 weeks in the sensory-to-motor repair (group III) revealed a significant (P < 0. 05) increase (104.4% +/- 22.9) in the relative response of peak-to-peak potentials when compared with group I (46.6% +/- 19) and group II (51.8% +/- 14.0). Muscle flap stimulation was most prominent at 6 weeks in sensory-to-motor reinvervated flaps (group III 133.1% +/- 25.4; group I 84.9% +/- 20.2). In this study, sensory-to-motor nerve repair significantly improved the sensibility of skin flaps at 6 weeks. Denervated flaps presented with 3 months of sensory recovery delay.

Animals↗
PubMed2000

[A model for allogenic extremity transplantation in the rat with possible microcirculatory monitoring].

A rat model for monitoring allograft rejection of transplanted rat hindlimbs at the microcirculatory level is described. The well-established rat cremaster flap model is combined with a rat hindlimb transplantation procedure at a level proximal to the neurovascular pedicle of the cremaster muscle. The cremaster serves as a microcirculatory monitor for in vivo evaluation of graft rejection by measuring skeletal muscle perfusion. Donor animals are male Lewis Brown Norway rats and recipients are Lewis rats. The right cremaster muscle of the donor animal is dissected as a tubular island flap and preserved in a subcutaneous tunnel in the hindlimb. Afterwards, the right hindlimb including the cremaster is amputated at the mid level of the common iliac vessels and transplanted to the recipient at the level of the external iliac vessels. Over a time period of five days, the cremaster muscle of the composite transplants showed appropriate tissue quality for intravital microscopical observations. This transplantation model allows evaluation of allograft rejection in vivo at the microcirculatory level.

Animals↗
PubMed2000

[Improving microcirculation of muscle flaps by tissue plasminogen activator in the rat cremaster muscle flap model].

Currently, tissue-plasminogen activator (t-PA) is the most potent and nevertheless safe fibrinolytic in clinical use. Its indications are fibrinolysis in acute myocardial infarction, ischemic stroke, deep vein thrombosis, pulmonary thromboembolism, as well as different kinds of peripheral arterial embolism. However, controlled studies on the effect of t-PA in microsurgery and free tissue transplantation are lacking. This study was designed to evaluate the effect of tissue-plasminogen activator on skeletal muscle flap perfusion after a thrombogenic stimulus. 24 male Sprague-Dawley rats were divided into four experimental groups of six animals each. In group 1, the cremaster was isolated as an end organ flap, in group 2 after cremaster isolation a semicircular inverted suture as a thrombogenic insult was performed at the ipsilateral common iliac artery. In group 3, local t-PA infusion followed the inverted suture and in group 4, vehicle was infused. After 24 hours, we measured cremaster muscle flap hemodynamics using intravital microscopy. Capillary perfusion significantly decreased after the inverted suture from 6.23 (group 1) to 1.50 (group 2) functional capillaries per visual field (medians). t-PA significantly increased capillary perfusion after the thrombogenic insult from 1.50 (group 2) and 2.50 (group 4) to 6.00 (group 3) (medians). Restoring capillary perfusion after a thrombogenic insult t-PA may increase flap survival rates.

Animals↗
PubMed2000

Robotic assistance in microsurgery.

The purpose of this study was to introduce a new robotic system for microsurgical procedures of the eye, ear, brain, face, and hand. The design and main features of the Robot Assisted MicroSurgery (RAMS) work station are described. In addition, compatibility with the operating-room table is assessed. The engineering components of the RAMS work station consist of a laptop computer, a joystick, a mouse, slave robot, VME and amplifier chassis, and safety control box. The mechanical part of the RAMS, the slave robot, is designed to simulate movements of the human upper extremity, which has five joints and six degrees of motion. The robot has a zero backlash in five joints, and can sustain full extension of loads over three pounds. The arm measures 2.5 cm in diameter, and it is 34.6 cm long from its base to its tip. The arm and its base weigh 2.5 kg. Motors and encoders on the robot are easily removable, allowing for the arm to be sterilized in an autoclave. Assessment of robotic positioning, time for setup, relative precision, and possible problems in the operating field are compared with human-assisted microsurgical procedures. Robotic arm positioning on the operating-room table differs for each type of procedure. For those involving the hand and upper extremity, the robotic arm base occupies 35 percent of the operating table; this is only 10 to 15 percent for human-assisted procedures. The setup time for robot-assisted procedures is longer than for human-assisted surgery. However, microsurgical manipulations with the RAMS are more rapid than the surgeon's motions. Therefore, depending on the type of procedure, the total operating time is comparable to human-assisted procedures. The movement of the RAMS was found to be more precise, in attempting to perform vascular and neural anastomoses. The authors conclude that concurrent use of the remote-controlled RAMS as a microsurgical assistant is applicable in microsurgery, with the advantages of greater precision and more rapid microsurgical manipulation. However, the long-term cost effectiveness of using this system as an assistant in microsurgery warrants further investigation.

Anastomosis, Surgical↗
PubMed2000

Microcirculatory window for early detection of allograft rejection.

The purpose of this study is to introduce a technical detail on a transplantation model for in vivo evaluation of microcirculatory changes during the acute phase of allograft rejection. The cremaster muscle is incorporated and transplanted along with the hind limb to detect and study ischemia/reperfusion injury and the acute phase of allograft rejection in rats. Thirty-six animals were studied in three experimental groups of 12 animals each. Each group was divided into subgroups and microcirculatory measurements were taken at two different time periods: 24 and 72 hours. In the ischemic control group (N = 12), cremaster muscles were denervated, prepared as a tube flap, and submitted to the same interval of ischemia as the other groups but without transplantation. In the isograft group (N = 12), rat hind limb-cremaster grafts were transplanted between genetically identical Lewis rats (RT11). In the allograft group (N = 12), 12 transplantations were performed across a major histocompatibility barrier between Lewis Brown-Norway (RT-11+/-n) and Lewis (RT 11) rats. The diameters of first-, second-, and third-order arterioles and venules; red blood cell velocities; and functional capillary density were recorded at 24 and 72 hours after transplantation. Daily follow-up observations were continued until 3 days after the first clinical signs of graft rejection. The mean number of perfused capillaries in the two transplantation groups was significantly lower than in the control group at both 24 hours and 72 hours (p < 0.05). Those results were as follows: 8.2 +/- 2.1 at 24 hours, 7.7 +/- 0.85 at 72 hours in the ischemic control group; 5.4 +/- 0.9 at 24 hours, 6 +/- 0.6 at 72 hours in the isograft group; and 5 +/- 0.9 at 24 hours, 5.5 +/- 0.3 at 72 hours in the allograft group. Red blood cell velocities and vessel diameters in the main arteries were also decreased in transplant groups at 24 hours (p < 0.05) but returned to normal 72 hours after the operation (p > 0.05). The composite rat hind limb-cremaster model presented in this study introduces a reproducible in vivo approach to monitor the differences in microcirculatory hemodynamics of ischemia/reperfusion injury and acute graft rejection. The model allows the study of the timing, sequence, and correlation between clinical and hemodynamic signs during the acute phase of allograft rejection.

Animals↗
PubMed2000

Improved perfusion after subcritical ischemia in muscle flaps treated with vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF), a potent endothelial mitogen, is secreted in ischemic tissue and plays a pivotal role in angiogenesis. We studied whether VEGF administered to a rat muscle flap at the time of ischemia induction would increase microcirculatory flow to the flap. The cremaster muscle flap was isolated on its neurovascular pedicle. Ischemia was induced by clamping the vascular pedicle, and 0.2 ml of either VEGF (0.1 microg) or vehicle (phosphate-buffered saline) was immediately infused into the muscle. After 4 or 6 hours, the clamps were released, and the cremaster was placed in a pocket in the medial thigh for 24 hours. The muscle was then dissected, and microcirculatory measurements were made under intravital microscopy. Six animals were used in each of the four groups. All flaps exposed to 6 hours of ischemia, the duration considered to be critical ischemia, had no significant microcirculatory flow, regardless of treatment with VEGF. In the 4-hour ischemia group, or subcritical ischemia group, red blood cell velocity in arterioles was 14 mm/sec in muscles treated with VEGF and 9 mm/sec in controls (p = 0.02), and capillary flow was 7 per high-power field in muscles treated with VEGF versus 2 per high-power field in controls (p = 0.0005). Thus, VEGF did not alter microcirculatory flow in a muscle flap exposed to critical ischemia, but it did enhance flow to a flap exposed to subcritical ischemia.

Animals↗