Yavuz Demir

Tolerance induction in composite facial allograft transplantation in the rat model.

Clinical application of composite tissue allograft transplants opened discussion on the restoration of facial deformities by allotransplantation. The authors introduce a hemifacial allograft transplant model to investigate the rationale for the development of functional tolerance across the major histocompatibility complex barrier. Eighteen rats in three groups were studied. The composite hemifacial allotransplantations including the ear and scalp were performed between Lewis-Brown Norway (RT1l+n) and Lewis (RT1l) rats and isotransplantations were performed between Lewis rats. Isograft controls (n = 6) and allograft controls (n = 6) did not receive treatment. Allografts in treatment group (n = 6) were treated with cyclosporine A 16 mg/kg/day during the first week; this dose was tapered to 2 mg/kg/day over 4 weeks and maintained at this level thereafter. Functional tolerance to face allografts was evaluated clinically and histologically. Donor-specific chimerism was assessed at days 21 and 63 by flow cytometry. In vitro evaluation of donor-specific tolerance was performed by mixed lymphocyte reaction at day 160 after transplantation. Isograft controls survived indefinitely. All nontreated allografts were rejected within 5 to 7 days after transplantation, as confirmed by histopathologic analysis. Five of six face allografts under the cyclosporine A protocol showed no signs of rejection for up to 240 days and remained alive and under evaluation, whereas one animal showed signs of rejection at day 140. This was reversed by adjustment of the cyclosporine A dose. At day 21 after transplantation, flow cytometric analysis of the donor-specific chimerism showed 1.11 percent of double-positive CD4FITC/RT1Ac-Cy7 and 1.43 percent of double-positive CD8PE/RT1Ac-Cy7 T-cell populations in the peripheral blood of hemiface allotransplant recipients. The chimerism level of double-positive CD4FITC/RT1Ac-Cy7 T cells increased to 3.39 percent, whereas it remained stable for the double-positive CD8PE/RT1Ac-Cy7 T-cell population at day 63 after transplantation (1.00 percent). The mixed lymphocyte reaction assay at day 160 after transplantation revealed donor-specific tolerance to donor (Lewis-Brown Norway) antigens and strong reactivity to the third-party (ACI) alloantigens. In this study, donor-specific chimerism and functional tolerance were induced in hemifacial allograft transplants across the major histocompatibility complex barrier under cyclosporine A monotherapy protocol. This model will allow further studies on tolerance induction protocols.

Development and maintenance of donor-specific chimerism in semi-allogenic and fully major histocompatibility complex mismatched facial allograft transplants

Background. The clinical application of composite tissue allograft transplants opened the discussion on the restoration of facial deformities by allotransplantation. We introduce a hemifacial allograft transplant model to investigate the rationale for the development of operational tolerance across a major histocompatibility complex (MHC) barrier. Material and Methods. Thirty rats were studied in five groups of six animals each. The composite hemiface isograft transplantations were performed in group 1. Allograft rejection controls included semi-allogenic transplantations from LBN (RT1l+n) donors (group 2) and fully allogenic transplantations from ACI (RT1a) donors (group 3) to LEW (RT1l) recipients. In the allograft treatment groups, recipients of LBN (group 4) and ACI donors (group 5) were treated with cyclosporine A monotherapy (16 mg/kg/day, tapered to 2 mg/kg/day). Face allografts were evaluated clinically and histologically. Donor-specific chimerism for MHC class I RT1n and RT1a antigens was assessed by flow cytometry. Mixed lymphocyte reaction for donor-specific tolerance in vitro was tested at day 160 posttransplant. Results. Isograft controls survived indefinitely. All nontreated allografts rejected within 5 to 8 days posttransplant. Long-term survival was achieved in 100% of LBN (up to 400 days) and ACI (up to 330 days) recipients. At day 160, posttransplant donor-specific chimerism was present in recipients of LBN (10.14% CD4/RT1n, 6.38% CD8/RT1n, 10.02% CD45RA/RT1n) and ACI (17.54% CD4/RT1a, 9.28% CD8/RT1a) transplants, and mixed lymphocyte reaction confirmed tolerance in recipients of LBN transplants and moderate reactivity in recipients of ACI allografts. Conclusion. Operational tolerance was induced in hemiface allograft transplants across an MHC barrier under cyclosporine A monotherapy protocol. It was associated directly with the presence of multilineage donor-specific chimerism.

Prospects for facial allograft transplantation in humans.

The face is a functional as well as an esthetic part of the body. It is the window through which we interact with others: two thirds of our communication is through nonverbal facial expressions. Reconstructing partial or full facial deformities caused by burns, trauma, or tumors still challenges most reconstructive surgeons. The ideal reconstructive procedure should address both the functional and esthetic units of the face.

Acrochordon and impaired carbohydrate metabolism.

Abstract Acrochordons were reported to have a probable association with diabetes mellitus but detailed data about this relation has not been introduced yet. We evaluated 120 patients with acrochordon for the presence of impaired carbohydrate metabolism. Overt diabetes mellitus (DM) was found in 88 patients and glucose intolerance was detected in 6 patients; 4 patients had reactive hypoglycemia. We concluded that acrochordons may be skin markers of underlying impaired carbohydrate metabolism and the patients with acrochordon should be evaluated for the presence of diabetes mellitus.

Cutaneous lobular capillary hemangioma induced by pregnancy.

Lobular capillary hemangioma, which is also named as pyogenic granuloma, is a common vascular proliferation of skin and mucous membranes. Hormonal influence in the development of lobular capillary hemangioma on the mucosal surfaces has been demonstrated but for cutaneous lesions located on the skin, this association has not been shown yet. In this report, a 25‐year‐old female patient with cutaneous lobular capillary hemangioma of the cheek induced by pregnancy is presented. The lesion was excised and lobular capillary hemangioma was given as diagnosis by histopathological evaluation. Estrogen receptor was weakly positive by immunohistochemical analysis. We suggest that elevated levels of estrogens during pregnancy may have an important role also on the development of cutaneous lobular capillary hemangiomas by direct hormonal action.

The effect of gradually increased blood flow on ischemia-reperfusion injury.

Even with excellent operative techniques, prolonged ischemic periods may cause unwanted results because of a complex mechanism called reperfusion injury. Various pharmacological and immunological agents have been used to prevent this type of injury. Another known way to diminish reperfusion injury is the gradual reperfusion of the ischemic tissues. In this study, the effect of a gradual increase in blood flow on ischemia-reperfusion injury of the skeletal muscle was investigated. The right hind limbs of 15 rats were partially amputated, leaving the femoral vessels intact. Preischemic femoral arterial blood flow was measured by using a transonic small-animal blood flowmeter (T106) in all animals. The rats were divided into three groups: Group I consisted of control rats; no ischemia was induced. Group II was the conventional clamp release group. Clamps were applied to the femoral vessels to induce 150 minutes of ischemia. The clamps were then released immediately and postischemic blood flow was measured. Group III was the gradual clamp release group. After 150 minutes of ischemia, clamps were released gradually at a rate so that the blood flow velocity would reach one fourth the mean preischemic value at 30 seconds, one half at 60 seconds, three fourths at 90 seconds, and would reach its preischemic value at 120 seconds. Total clamp release was allowed when blood flow was less than 1.5 fold of the preischemic values. Postoperatively the soleus muscles were evaluated histopathologically, and malonyldialdehyde and myeloperoxidase levels were measured. The mean preischemic blood flow was 13.6 ± 2.24 ml per kilogram per minute in all groups. In the conventional release group, postischemic flow reached four to five fold its preischemic values (61.06 ml per kilogram per minute). Histopathology revealed more tissue damage in the conventional release group. Malondialdehyde and myeloperoxidase levels were also significantly lower in the gradual release group. Depending on histological and biochemical findings, a gradual increase in blood flow was demonstrated to reduce the intensity of ischemia-reperfusion injury in the soleus muscle of this animal model.Ünal Ş, Özmen S, Demİr Y, et al. The effect of gradually increased blood flow on ischemia-reperfusion injury. Ann Plast Surg 2001;47:412–416

Surgical management of penoscrotal lymphangioma circumscriptum.

Lymphangioma circumscriptum of the penis and scrotum is an unusual entity that may be indistinguishable from genital warts. After confirmation of the diagnosis, a treatment plan consisting of wide excision should be outlined. To lower the chance of recurrence, not only the affected skin but all the subjacent subcutaneous tissue, including the deeper components of the lymphatic malformation just above the deep fascia, should be removed.

Variations of supraorbital foramina in living subjects evaluated with multidetector computed tomography

We aimed to evaluate the anatomic variations of supraorbital foramina/notches in living subjects using multidetector CT (MDCT) related to age, sex, and side.

Repair of Peripheral Nerve Defects With Epineural Sheath Grafts

In this study, we investigated the potential of using a detubulized flat epineural sheath for bridging nerve gaps as an alternative to nerve autografting. Nerve gaps were created by removing a 1.2-cm segment of sciatic nerves. Later, the epineurium was incised longitudinally, and after fascicle removal, a flat rectangular epineural sheath was created. Five experimental groups (6 rats each) included: autograft and no treatment controls and epineural sheath groups repaired with 1 strip, 2-strip, and full epineural sheath grafts. Assessments performed at 3, 6, and 12 weeks included functional (pinprick, toe-spread), neurosensory (somatosensory-evoked potentials), and histomorphometric evaluations. The functional results of toe-spread, somatosensory-evoked potentials, and histomorphometric data revealed comparable outcomes between autograft, 2-strip, and full sheath grafts, indicating adequate nerve regeneration. Thus, the new epineural sheath graft technique introduced in this study can be considered as an alternative method to standard nerve autografting technique.

Effect of early nerve release on the progression of neuropathy in diabetic rats.

Diabetic neuropathy renders the peripheral nerves to be more susceptible to compression at potential entrapment sites. We evaluated the effects of “prophylactic” decompression procedures on the progression of diabetic neuropathy in an experimental model. Thirty diabetic Zucker rats were studied. Group I, II, and III rats were followed up for 12 weeks and IV, V, and VI rats for 24 weeks. Group III and VI rats served as short- and long-term controls without any surgical intervention. Group I and IV rats had tarsal tunnel release (TTR); group II and V rats had TTR and peroneal nerve release (PNR) procedures on their left legs. Nerve function was assessed by pinprick, toe spread tests, sciatic function index (SFI), somatosensory evoked potential (SSEP) analysis, and gastrocnemius muscle wet weight measurements. SFI analysis revealed a statistically significant difference between the combined TTR-PNR and nonoperative control groups at both short- and long-term follow-up (P ≤ 0.01). SSEP result analysis of operated left and nonoperated right sides revealed a statistically significant difference in P1 latency values at both short- and long-term follow-up (P < 0.05). We confirmed beneficial effects of decompression procedures at early onset of diabetes before the metabolic nerve injury advanced into an axonal loss.