Nihan Haberal

Structural consequences after intravitreal bevacizumab injection without increasing apoptotic cell death in a retinopathy of prematurity mouse model

Purpose:  To evaluate the effect of different bevacizumab concentrations on retinal endothelial cell proliferation, retinal structures and apoptotic activity after intravitreal injection in a retinopathy of prematurity (ROP) mouse model.

Vascular Endothelial Growth Factor Expression and Cyclosporine Toxicity in Renal Allograft Rejection

The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF‐α, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow‐up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF‐α expressions (p < 0.001). VEGF expression increased with increasing expression of TNF‐α (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow‐up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.

Doxycycline causes regression of endometriotic implants: a rat model.

BACKGROUND Doxycycline (Dox) has a number of non-antibiotic properties. One of them is the inhibition of matrix metalloproteinase (MMP) activity. The aim of this study was to assess the effects of Dox in a rat endometriosis model. METHODS Endometriosis was surgically induced in 40 rats by transplanting of endometrial tissue. After 3 weeks, repeat laparotomies were performed to check the implants and the animals were randomized into four groups: Group I, low-dose Dox (5 mg/kg/day); Group II, high-dose Dox (40 mg/kg/day); Group III, leuprolide acetate 1 mg/kg single dose, s.c.; and Group VI (controls), no medication. The treatment, initiated on the day of surgery and continuing for 3 weeks, was administered to the study groups. Three weeks later, the rats were euthanized and the implants were evaluated morphologically and histologically for immunoreactivity of MMP-2 and -9, and interleukin-6 (IL-6) concentration in the peritoneal fluid was assayed. RESULTS Treatment with leuprolide acetate, or high-dose or low-dose Dox caused significant decreases in the implant areas compared with the controls (P = 0.03, P = 0.006, and P = 0.001, respectively). IL-6 levels in peritoneal fluid decreased in Group I (P = 0.02) and Group III (P < 0.05). MMP H scores were significantly lower in the group that received low-dose Dox in both epithelial and stromal MMP-2 and -9 immunostaining when compared with the control group [P = 0.048, P = 0.002, P = 0.007 and P = 0.002, respectively, MMP-2 (epithelia), MMP-2 (stroma), MMP-9 (epithelia) and MMP-9 (stroma)]. CONCLUSIONS Low-dose Dox caused regression of endometriosis in this experimental rat model.

Effect of static magnetic field on experimental dermal wound strength.

Context: An animal model. Aim: We sought to evaluate the effect of static magnetic fields on cutaneous wound healing. Materials and Methods: Male Wistar rats were used. Wounds were created on the backs of all rats. Forty of these animals (M group) had NeFeB magnets placed in contact with the incisions, either parallel (Pa) and perpendicular (Pr) to the incision. The other 40 animals (sham [S] group) had nonmagnetized NeFeB bars placed in the same directions as the implanted animals. Half of the animals in each group were killed and assessed for healing on postoperative day 7 and the other half on postoperative day 14. The following assessments were done: gross healing, mechanical strength, and histopathology. Statistical Analysis Used: Intergroup differences were compared by using the Mann-Whitney U or t test. Values for P less than 0.05 were accepted as significant. Results and Conclusions: There were no differences between the magnetic and sham animals with respect to gross healing parameters. The mechanical strength was different between groups. On postoperative day 14, the MPr14 had significantly higher scores than the other groups. When static, high-power, magnetic fields are placed perpendicular to the wound, increased wound healing occurs in the skin of the experimental model.

Hydrops fetalis in a neonate with down syndrome, transient myeloproliferative disorder and hepatic fibrosis.

Transient myeloproliferative disorder is a self limiting disorder characterized by leukocytosis with the presence of megakaryoblasts in the peripheral blood and bone marrow, anemia, thrombocytopenia, and organomegaly. It occurs in approximately 10% of newborn infants with Down syndrome. Hepatic fibrosis is seen in the severe form of transient myeloproliferative disorder with Down syndrome that is characterized by diffuse intralobular sinusoidal fibrosis and extramedullary hematopoesis. We describe a patient with hydrops fetalis, Down syndrome, and transient myeloproliferative disorder. We suggest that patients with the severe form of transient myeloproliferative disorder should be examined for hepatic fibrosis.

Evaluation of neointimal hyperplasia on tranilast-coated synthetic vascular grafts: an experimental study.

Tranilast is an antiallergic drug that interferes with proliferation and migration of vascular smooth muscle cell induced by platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1). We investigated the local effect of tranilast on neointimal hyperplasia using tranilast-coated prosthetic grafts. The inner sides of the thin-walled polytetrafluoroethylene (PTFE) grafts were coated with chitosan and tranilast containing chitosan solution. Wistar albino rats (32) were used in the study. Patches (1 × 2 mm) for vascular grafts were prepared. Three groups were tested: group 1 (n = 12; tranilast coated), group 2 (n = 10; adhesive-only film-layer–coated), and group 3 (n = 10; normal ePTFE patch grafts sutured to the carotid arteries of the rats). Recipient sites of the carotid arteries were excised 4 weeks after surgery. All sections were examined histologically for graft patency, thrombus formation, and neointimal thickness. Expression of PDGF, fibroblast growth factor, and TGF-β1 on cross-sections of the neointima were evaluated by immunohistochemistry. No significant differences were found regarding mean neointimal thicknesses. PDGF and TGF-β-1 expressions were significantly lower in group 1. Although a decrease in local effect of tranilast was observed for growth factor expressions at a drug concentration of 0.05 mg/cm2, a significant reduction in neointimal hyperplasia was not achieved. The coating concentration of 0.05 mg/cm2 may have been too low to produce an antiproliferative effect. Given our promising results, further studies are recommended and planned using different drug concentrations and time intervals.

Focal Amyloidosis of the Orbit Presenting as a Mass: MRI and CT Features

Focal orbital amyloidosis is a rare entity and little is known about its magnetic resonance imaging (MRI) features. In this case report, imaging features of a case of focal orbital amyloidosis presenting as a mass have been documented together with its histopathological findings. On MRI, a well-defined mass was seen as isointense with rectus muscle on T1-weighted images and heterogeneously hypointense on T2-weighted images. Punctuate calcifications were observed on the computerized tomography (CT) examination.

Malignant intraperitoneal mesothelioma-Başkent University experience

OBJECTIVE To evaluate diagnostic and treatment results of malignant intraperitoneal mesothelioma in one setting. MATERIALS AND METHOD 12 patients treated for malignant peritoneal mesothelioma from January 2007 to June 2009 in Başkent University Ankara Hospital, Department of Gynaecology and Obstetrics were evaluated. In a retrospective observational study design tumour stage, grade, differentiation, time from first symptoms, pleural involvement, peritoneal cancer index, surgical cytoreduction, chemotherapeutic regimen, number of cycles, disease free survival and overall survival were evaluated. Disease free survival, overall survival, time until first symptoms were researched. RESULTS The main presenting symptom was abdominal distension. Primary cytoreductive surgery followed by chemotherapy was performed in 9 patients. In 6 patients completeness of cytoreductive score below 2 was achieved. As a first line chemotherapy the most often used was cisplatin in combination with pemetrexed. Themean time from first symptoms until the diagnosis was 1.9 months. Disease free survival of 4.4±1.0 months after completing particular treatment and overall 1-year survival of 85.7 % was observed. No correlations between first symptoms (0.27, p=0.52), time until the diagnosis (-0.29, p=0.44) and overall survival were observed. Similarly, correlations between peritoneal cancer index (0.25, p=0.67), prior surgical score (-.45, p=0.37), completeness of cytoreduction score (0.61, p=0.27) and overall survival were not observed. CONCLUSIONS Because of the low number of patients and different treatment approaches data from a particular patient setting are inconclusive, but from the literature there is evidence that patients with malignant intraperitoneal mesothelioma should undergo optimal cytoreduction and receive a combination of cisplatin and pemetrexed as a first line chemotherapy for intravenous or cisplatin in different chemotherapy regimens using the intraperitoneal administration route, if accessible, with even higher overall survival rates.

Experience of Post-Transplant Lymphoproliferative Disorder (PTLD) After Pediatric Liver Transplant: Incidence, Outcomes and Association with Food Allergy

Introduction We evaluated our 16 years of experience of pediatric PTLD cases who were liver transplanted in Başkent University Hospital between 2001-2017 years. Materials and Methods We reviewed the clinical and laboratory data of 8 patients who were diagnosed as PTLD out of 236 pediatric patients who were liver transplanted in Başkent University Hospital between 2001-2017 years. Pretransplant EBV statuses of 172 patients were also recorded. Results The total PTLD incidence was 3.4%. The incidence of PTLD was 10% in pretransplant EBV IgG negative patients, while it was 0.8% in pretransplant EBV seropositive patients. Mean age of the patients at liver transplant was 2.71±3.21 years; four patients were under 1 year of age at the time of transplant. PTLD was diagnosed 21.81±18.1 months after transplant. The primary site of involvement was variable among patients: peripheral and mediastinal lymph nodes, stomach-intestinal, transplanted graft, bone marrow, and nasopharynx. Eosinophil count varied greatly among patients, with mean values of 524.62±679. Food allergy prevalence was higher than the non-PTLD patients (23/236; 10% versus 3/8; 37.5%) The lymphoproliferative disease was of B cell origin in 6 of the patients. One patient died due to neutropenic sepsis during chemotherapy, while seven patients are being followed up in full remission for 7.75±4 years. Conclusion PTLD is a life-threatening complication of solid organ transplantation with a heterogenous clinic. Food allergy had a close association with PTLD. Close follow-up of patients who had risk factors and early diagnosis with appropriate treatment may lead to good outcome.

A single-center experience of post-transplant lymphoproliferative disorder (PTLD) cases after pediatric liver transplantation: Incidence, outcomes, and association with food allergy

BACKGROUND/AIMS We evaluated our 16-year single-center experience of pediatric post-transplant lymphoproliferative disorder (PTLD) cases who underwent liver transplantation between 2001 and 2017. MATERIALS AND METHODS Of the 236 pediatric patients who underwent liver transplantation between 2001 and 2017, the clinical and laboratory data of eight patients diagnosed with PTLD were reviewed. The pre-transplant Epstein-Barr virus (EBV) status of 172 patients was also recorded. RESULTS The total incidence of PTLD was 3.4%. The incidence of PTLD was 10% in pre-transplant EBV immunoglobulin G (IgG)-seronegative patients and 0.8% in pre-transplant EBV IgG-seropositive patients. The mean age of the patients at liver transplantation was 2.71±3.21 years, and four patients were aged below 1 year at the time of transplantation. PTLD was diagnosed at 21.81±18.1 months after transplantation. The primary site of involvement was variable among patients: peripheral and mediastinal lymph nodes, stomach and intestine, transplanted graft, bone marrow, and nasopharynx. The eosinophil count varied greatly among patients, with a mean value of 524.62±679/mm3. Three patients had a food allergy and were administered an elimination diet at the time of PTLD diagnosis. Six patients had PTLD of B-cell origin. One patient died due to neutropenic sepsis during chemotherapy, whereas seven patients were followed up in full remission for 7.75±4 years. CONCLUSION PTLD is a life-threatening complication of solid-organ transplantation with a heterogeneous clinical spectrum. Food allergy had a close association with PTLD. A close follow-up of patients with risk factors and an early diagnosis with appropriate treatment may lead to a better outcome.