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Biomedical subjects

K Ozer

Publications and source records attributed to K Ozer.

10 recordsLinked to original sources

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↗

Frontal chondrosarcoma in a cat.

In this case, chondrosarcoma, detected on the frontal bone of a 12-year-old female cross-bred cat was examined clinically and histopathologically. After being processed routinely, specimens were stained with Hematoxylin & Eosin and Crossman Modification of Mallars Triple Stain. The neoplasm was composed of numerous fusiform mesenchymal cells intimately associated with the formation of lobular structure, separated by thin fibrous septae. In the center there were observed atypical chondrocytes, forming the matrix of the tumoral mass, surrounded by round-ovoid, fusiform mesenchymal cells having interference with the septal tissue at the periphery. Few mitotic figures were detected in these areas. The tumors pattern, localization, the species and the age of the animal were consistent with those of multilobular chondroma known as chondroma rodens. Although the mitotic figures and the wide atypia indicated that the entity was a neoplasm of malign type, it was more likely considered to be the malign transformation of chondroma rodens. The post-surgical outcome of the patient was observed, and recurrence on the same site was reported within 2 months.

Animals↗

Restoration of sensibility in irreparable ulnar and median nerve lesions with use of sensory nerve transfer: long-term follow-up of 20 cases.

A prospective study was conducted to evaluate patient outcomes following sensory nerve transfer. Twenty patients with irreparable ulnar or median nerve lesions underwent the procedure. Nerve involvement was bilateral in 5 cases. The mean age of the patients at the time of surgery was 29 years. The mean paralysis time and the average length of follow-up were 59 and 78 months, respectively. Eighteen of 20 patients attended a sensory re-education program after surgery. Outcome was assessed objectively by functional sensory recovery testing and by the British Medical Research Council standards. Subjective outcome was assessed by a questionnaire. Two-point discrimination of less than 10 mm was achieved in 15 of 25 hands. The mean functional sensory recovery score was 83. Eighteen of 20 patients reported that the function of their hands improved after the procedure. Good or excellent results were associated with immediate transfer of the nerve, young age, and patients' attendance to the sensory re-education program after surgery. No differences were found between the recovery of ulnar and median nerves. Based on these results we suggest that sensory nerve transfer is a simple and reliable way of restoring sensibility to the hand with favorably comparable results over conventional nerve grafting in selected cases.

Adolescent↗

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↗

Acute alterations in muscle flap microcirculation during tumor necrosis factor alpha-induced inflammation.

In reconstructive microsurgery of free tissue transfer, ischemia-reperfusion (IR) injury is an unavoidable component of the procedure, which can affect free flap survival markedly. A notable amount of evidence implicates neutrophils in IR injury. Transforming necrosis factor alpha (TNF-alpha) is known to have a central role as a mediator of neutrophil activation in IR injury. The effect of inflammatory stimuli, TNF-alpha, on flow hemodynamics and leukocyte-endothelial interactions in the muscle flaps submitted to IR injury was investigated. In group 1, 6 rats were administered 1 ml of vehicle solution. In group II rats (N = 6), 1 ml of recombinant human TNF-alpha (10 ng per milliliter) was injected intra-arterially. After an hour of ischemia, the cremaster muscle flaps were monitored at 1-hour intervals during 6 hours of reperfusion. After clamp removal, the number of rolling, adhering, and transmigrating leukocytes in the TNF-alpha group was increased by 4-fold, 3-fold, and 3.5-fold respectively compared with the control group (p < 0.05). The increase in rolling leukocytes continued for as long as 3 more hours, whereas the number of adhering and transmigrating leukocytes remained high throughout the experiment. A significant increase in the diameters of the third- and fourth-order arterioles in the TNF-a group was accompanied by a decrease in the number of flowing capillaries at all intervals (p < 0.05). The effect of TNF-alpha-induced inflammation on leukocyte activation was found to be maximal during the first 3 hours of reperfusion. The vasodilatory effect of TNF-alpha was observed only on the third- and fourth-order arterioles.

Animals↗

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↗

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↗

In vivo microscopic assessment of cremasteric microcirculation during hindlimb allograft rejection in rats.

Experimental and clinical studies of vascular allogenic extremity transplantation have yielded disappointing results and have not been clinically useful. With recent advances in transplantation immunology, considerable interest has focused on the understanding of leukocyte-endothelial interaction at the microcirculatory level. The objective of this study was to characterize the alterations in leukocyte-endothelial interaction in the early stages of rat hindlimb allograft rejection. To study the changes at the microcirculatory level, a new microsurgical model was developed; the cremaster muscle was incorporated into the transplanted hindlimb. The purpose of this study was to report on the microcirculatory changes during rat hindlimb allograft rejection. A total of 24 transplantations were performed among the four experimental groups. In a control group, 12 rat hindlimb-cremaster grafts were transplanted between genetically identical animals, Lewis to Lewis. Microcirculatory measurements of graft survival were taken at 24 hours (group 1A, n = 6) and at 72 hours (group 1B, n = 6). In the rejection control group, 12 transplantations were performed across a major histocompatibility barrier between Lewis-Brown Norway and Lewis rats. Microcirculatory measurements were taken at 24 (group 2A, n = 6) and 72 hours (group 2A, n = 6) as above. The following parameters were evaluated to discover the leukocyte-endothelial interaction: endothelial edema index and the number of rolling, adherent, and transmigrating leukocytes and lymphocytes in the postcapillary venule. Physical signs of limb rejection, such as edema, erythema, scaling, plaque formation on the skin, hair loss, and skin surface temperature, were monitored. Microcirculatory signs of rejection included the following. There was a significant increase in the number of adherent leukocytes in allograft transplants at both 24 hours (205 percent; 2.05 +/- 0.38) and 72 hours (431 percent; 9.11 +/- 3.41) when compared with isograft controls (1.00 +/- 0.89 at 24 hours; 2.11 +/- 0.34 at 72 hours) (p < 0.05). The activation of leukocyte transmigration increased more than 7-fold in muscle allografts at 24 hours (0.55 +/- 0.25 versus 4.16 +/- 1.89) and more than 6-fold at 72 hours (0.72 +/- 0.38 versus 4.38 +/- 1.28) after transplantation (p < 0.05). Endothelial edema index, a measure of endothelial swelling and cellular deposit accumulation, increased more than 119 percent in the allograft group 72 hours after transplantation (1.23 +/- 0.07 versus 1.46 +/- 0.09) (p < 0.05). The first clinical signs of limb rejection were scaling of the skin or hair loss; they were observed between the seventh and ninth postoperative days. The composite rat hindlimb-cremaster model presented in this study introduces a new in vivo approach to monitor acute graft rejection using the intravital microscopy system. This is a valuable model for defining the timing, sequence, and correlation between immunologic events and clinical signs during the acute phase of allograft rejection.

Abdominal Muscles↗

Effects of 8-Gy radiation on the microcirculation of muscle flaps in the rat.

Combination of radical excision and radiation has been used as a treatment modality for cancer patients. As a result, in reconstructive surgery there is often a need to harvest flaps in the vicinity of previously irradiated tissues. Radiation has been shown to cause progressive injury to the macrocirculation and microcirculation, often jeopardizing flap survival. The purpose of this study was to examine whether radiation significantly affects the sequence of leukocyte-endothelial interactions or the hemodynamics of the muscle flap in both acute and chronic situations. Male Sprague-Dawley rats (n = 42) were divided into seven groups of six rats each. Rats in group I were not irradiated. Groups II through VII received 8-Gy radiation to the right groin and scrotum. Groups II, III, and IV were examined at 4, 24 and 72 hours, respectively, and groups V, VI, and VII were examined at 1, 2 and 12 weeks. For intravital microscopy, the cremaster muscle was dissected on its neurovascular pedicle. Vessel diameters and red blood cell velocities were measured in the central cremasteric branches and branch arterioles. Capillary perfusion was evaluated in 27 visual fields of each flap. Leukocyte-endothelial interactions were evaluated by numbers of rolling, adhering, and transmigrating leukocytes in post-capillary venules. In the same postcapillary venule, we measured the endothelial edema index (constriction index). The hemodynamics of irradiated flaps did not differ significantly from those of controls. Diameter and red blood cell velocity were increased in the first- and second-order arterioles and were highest at 72 hours and 1 week. After irradiation, third-order arterioles were constricted. Radiation reduced capillary perfusion by 4.3, percent. None of the differences were statistically significant. Neither leukocyte behavior nor the constriction indices differed among the groups. In conclusion, low-dose radiation of 8 Gy does not affect hemodynamics or leukocyte-endothelial interactions of muscle flaps in the rat. Muscle tissue with intact microvasculature can be harvested for reconstructive procedures after low-dose radiation.

Animals↗

Primary epiploic appendagitis: CT manifestations.

Inflammation of an epiploic appendage is considered to be a rare cause of acute abdomen. Recently, it has been reported that typical computed tomography (CT) findings of primary epiploic appendagitis (PEA) provide a definitive diagnosis in most of the cases. However, since these papers are only few, they are easily overlooked by the practicing radiologists. Our purpose is to add four new cases to the existing literature and to perform a review of the literature.

Abdomen, Acute↗