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Biomedical subjects

B Demirhan

Publications and source records attributed to B Demirhan.

At least 19 recordsLinked to original sources

Posttransplant tubulointerstitial nephritis: clinicopathological correlation.

As a cause of graft dysfunction, tubulointerstitial nephritis (TIN) seems to be the third most common pathology after rejection and cyclosporine nephrotoxicity. Among 540 needle biopsies obtained from 280 renal transplant patients between 1996 and 1999, acute TIN was detected in 23 patients (8%). The cause of acute TIN was secondary to bacterial infection in 17 patients and secondary to cytomegalovirus (CMV) infection in three patients. The remaining three cases showed granulomatous pyelonephritis due to Mycobacterium tuberculosis (n = 2) and Candida albicans (n = 1). During follow-up, 13 of 23 patients (56.5%) showed at least one acute rejection episode. The average number of urinary tract infection (UTI) episodes in the 23 patients was 1.4 +/- 07. We observed that the number of UTI episodes showed a significant association with the development of chronic allograft nephropathy (P = .03) and graft loss (P < .01). Twelve patients (52.2%) lost their grafts during 5 years posttransplantation. Only 6 of 17 patients with bacterial TIN lost their graft at a mean time of 52.5 +/- 14 months. But all patients with CMV TIN or granulomatous TIN lost their grafts at a mean time of 31 +/- 3.1 months and 39 +/- 3 months, respectively (P < .05). In conclusion, these results support the pathological role of tubulointerstitial nephritis as a pathway of graft rejection or renal allograft deterioration among recipients after transplantation.

Adult↗

Frequency of recipient-derived chimerism and relationship with acute rejection and HLA tissue typing in transplanted livers.

BACKGROUND: We sought to determine the extent and time course of recipient-derived chimerism after transplantation and the relationship with acute rejection episodes (ARE) and HLA typing in hepatic allograft patients. PATIENTS AND METHODS: We studied 18 needle liver biopsy specimens from patients who had undergone orthotopic liver transplantation. Fluorescent in situ hybridization (FISH) analysis for X and Y chromosomes was performed in all cases with a sex mismatch. To evaluate the HLA matching, we used serological and polymerase chain reaction (PCR) methodology. RESULTS: There was a sex mismatch between the recipients and donors in all cases. X and Y chromosome chimerism was detected in 14 of 18 (83%; 31.14 +/- 27.4) patients. Also, no statistical association was found between the presence and the extent of chimerism and clinicopathological parameters (P < .05). CONCLUSIONS: Our results suggest that chimerism was frequently seen in liver allografts, but it did not influence the occurrence of ARE, tissue compatibility, or histopathological changes in the posttransplantation period. The clinical, immunological, and histopathological relevance of chimerism remain unclear. These results may relate to the small number of patients and disproportion of chimerism-positive versus-negative cases. Further prospective studies will be required to clarify these findings in a larger population of liver transplant patients.

Adolescent↗

Hepatic stellate cells in biopsies from liver allografts with acute rejection.

BACKGROUND: [corrected] Hepatic stellate cells (HSCs) are nonparenchymal elements that play a major role in fibrogenesis due to various pathologies. HSCs are easily activated by certain injuries, which produce contraction and relaxation of HSCs, resulting in hepatic microcirculatory disturbances. The present study sought to analyze the expression of alpha-smooth muscle actin (alpha-SMA) positive HSCs in liver allografts during acute rejection episodes (ARE), determining whether it was related to the pathogenesis of this immune response. MATERIALS AND METHODS: Using immunohistochemistry and a semiquantitative scoring system, the expression of alpha-SMA in HSCs was analyzed in liver allografts with ARE (group 1, n = 64) or without ARE (group 2, n = 20). Normal liver tissue from transplant donors (group 3, n = 53) served as the control materials. RESULTS: Significantly more alpha-SMA positive HSCs were found in group 2 than in the other two groups (P < .05). The minimal difference observed between groups 1 and 3 was not statistically significant. As well, no statistical association was found between expression of alpha-SMA and the clinical parameters of age, gender, etiology of liver failure, donor type (partial or whole), posttransplantation period, and liver function tests. CONCLUSIONS: While these results represent preliminary findings, it may be possible that HSC expression is a protective mechanism during ARE in hepatic allograft patients. If this is true, enhanced expression of this protein may mitigate ARE in liver allograft patients.

Actins↗

Liver transplantation in children weighing less than 10 kilograms.

Orthotopic liver transplantation (OLT) remains a major medical and surgical challenge in small pediatric patients. From April 2003 through October 2005, 17 infants (each of whom weighed less than 10 kg) underwent the procedure. Four were girls and 13 were boys (mean age, 15.7 +/- 9.3 months [range, 2-36 months]; mean weight at the time of transplantation, 7.4 +/- 2.6 kg [range, 6-10 kg]). All transplants were obtained from living-related donors. Sixteen left lateral segments and 1 left lobe were transplanted. The median graft-to-recipient weight ratio was 3.5% +/- 1.2% (range, 1.5%-6.1%). During the early postoperative period, hepatic arterial thrombosis was identified in 2 infants, and a biliary leak in 1. Hepatic arterial thrombosis was treated by reanastomosis with polytetrafluoroethylene grafting in the first patient and by surgical embolectomy in the second. The biliary leak was treated with percutaneous drainage. In 1 infant, portal vein stenosis, which was identified during the late postoperative period, was treated by percutaneous balloon dilatation. At this time, 14 (82.3%) infants were alive, exhibiting good graft function at a median follow-up of 11 months (range, 2-36 months). Three infants died: 1 on postoperative day 47 from adult respiratory distress syndrome, 1 on postoperative day 12 from sepsis, and 1 on postoperative day 65 from sepsis associated with EBV infection. Episodes of acute rejection, which occurred in 5 patients, were treated with pulse steroid therapy. On follow-up, histologic examination revealed hepatocellular carcinoma in 2 infants and Burkitt's lymphoma in 1 infant. Our data confirm that extensive use of living-related donors in liver transplantation can result in an excellent outcome for small pediatric patients.

Anastomosis, Surgical↗

Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters.

Angiogenesis plays an important role in tumor growth, metastasis, and prognosis. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen and acts on the angiogenic stimulation of human neoplasias. In infiltrative ductal carcinoma (IDC), VEGF expression is correlated with high vascularity. Tumor-associated macrophages (TAMs) contribute to tumor proliferation, progression and angiogenesis and have a complex role in tumor biology. In this study, the correlations between microvessel density (MVD), VEGF expression, and TAMs and their relations to clinicopathological parameters such as tumor size, metastatic lymph node, mitotic activity index (MAI) and tumor grade were investigated in 48 cases of IDC and 30 infiltrative lobular carcinoma (ILC) cases. MVD showed a significant positive correlation with TAMs, VEGF, metastatic lymph nodes, tumor size and grade in IDC (P < 0.001). In ILC, MVD and tumor size were positively correlated (P = 0.003), while MVD was not correlated with VEGF, TAMs, MAI, metastatic lymph nodes, and grade. These findings are suggestive of angiogenesis stimulation in IDCs by VEGF, driving the macrophages into the tumor area. MVD and TAMs were found to be important prognostic factors in IDCs. On the other hand, however, VEGF did not contribute to angiogenesis in ILCs, and MVD and TAMs did not have any prognostic significance. These results suggest the involvement of factors not related to VEGF in the angiogenesis of lobular carcinoma.

Adult↗

Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum.

We report successful treatment of a refractory myelodysplastic syndrome-associated pyoderma gangrenosum with the combination of thalidomide and interferon-alpha2a in a single patient. A non-healing wound developed on a 40-year-old woman's left thumb after minor trauma. Massive ulcerovegetative lesions developed after reconstruction surgery. Histopathological examination of the bone marrow and cytogenetic studies revealed an atypical myeloproliferative/myelodysplastic syndrome. The skin lesions resolved dramatically after two months of thalidomide and interferon-alpha2a combination therapy and the haematological status improved.

Adult↗

Cholesterol crystal embolization mimicking vasculitis: success with corticosteroid and cyclophosphamide therapy in two cases.

Cholesterol crystal embolization is a potential complication of atherosclerosis. Approximately one-third of the patients who develop this problem have a history of vascular surgery, angiography or angioplasty hours to weeks before onset. The skin and the kidneys are most frequently involved, but any organ can be affected. Livedo reticularis of the lower extremities and acrocyanosis (known as "blue toe syndrome") are the most common cutaneous manifestations. Histological examination is the only way to definitively diagnose cholesterol crystal embolization. Recently, it has been proposed that cholesterol embolization is associated with vasculitis, and some authors have labeled this condition a "vasculitis look-alike." There is still no specific treatment for this problem, even in cases that progress to renal failure. However, a few case reports in the literature have noted successful treatment with corticosteroids and cyclophosphamide in patients with deteriorating renal function. In this article, we describe two cases of severe cholesterol crystal embolization accompanied by renal dysfunction) and blue toe syndrome. Both patients benefited from corticosteroid and cyclophosphamide therapy.

Aged↗

Ki-67 proliferation index in Kaposi's sarcoma after renal transplantation: findings in skin-only cases versus cases with internal-organ involvement.

Kaposi's sarcoma (KS) is an angioproliferative condition that accounts for 6% of all malignancies in organ transplant patients. When we review the literature, the results of the studies comparing the different stages and the proliferative activity of the tumor are challenging. However, we found no previous study on Ki-67 protein expression in KS that correlates skin and organ lesions. In the current study, we investigated whether there is a correlation on the proliferative activity between skin and internal organ lesions in KS. Proliferative activity of 13 biopsy specimens of KS was assessed immunohistochemically using the monoclonal antibody MIB-1 (Ki-67). Mann-Whitney U test is used for statistical analysis and a P value < .05 was considered significant. Seven of 13 cases were skin and six were internal organ KS. For skin lesions, the mean MIB-1 proliferation index was 14.5%, and it was 13% for organ lesions. There was no significant association between skin and internal organ KS in regard to MIB-1 PI (P > .05). The findings suggested that the proliferative activity in KS does not differ in skin and organ lesions. On the other hand, it should be considered that the number of cases in our study was limited and further studies with a larger series are needed.

Adult↗

The role of early colonoscopy in CMV colitis of transplant recipients.

Cytomegalovirus (CMV)-associated diseases remain a major problem in transplant recipients. Early diagnosis is critical. Presentation of early CMV colitis can be mild and nonspecific in transplant recipients. Although serology is helpful in the diagnosis, sometimes it is inadequate. Because the endoscopic features of CMV colitis are specific, colonoscopy facilitates the histopathologic examination. We present the clinical properties and advantages of early colonoscopy in transplant recipients with CMV colitis. The study group included seven patients (six men, one woman of mean age, 36.7 years (range, 22 to 64 years) whose mean transplant duration was 12.3 months (range, 1 to 72 months). Six of the seven patients experienced an acute graft rejection treated with high doses of steroids; one patient had a herpes simplex virus infection. All patients were on steroid treatment with a various combinations of immunosuppressive agents, including cyclosporine, mycophenolate mofetil, and tacrolimus. All patients presented with mild diarrhea without any blood or mucous discharge. Four patients had fever exceeding 38 degrees C; two had abdominal pain. Stool examinations revealed normal findings in six patients, while one patient had white blood cells and amoebic cysts. Serum CMV IgM and CMV pp65 antigenemia were negative in five of seven patients and two had positive results. All patients showed typical colonoscopic and histopathologic findings compatible with CMV colitis. Standard ganciclovir treatment was successful in all patients. Early and rapid colonoscopy is beneficial for the early diagnosis and management of CMV colitis in transplant recipients.

Adult↗

The significance of Tc-99m DTPA renal scintigraphy for the demonstration of progressive functional changes that accompany chronic allograft nephropathy.

OBJECTIVES: Chronic allograft nephropathy (CAN) is usually progressive; its natural course can only be modified in the initial stages. In this study, we graded Tc-99m diethylenetriaminepentaacetic acid (DTPA) renogram curves with respect to the perfusion/uptake pattern and correlated these findings with biopsy results in patients with CAN. METHODS: This study included 63 renal allograft recipients with biopsy-proven CAN. The agent used for renal scintigraphy was Tc-99m DTPA. Quantitative evaluation of perfusion included calculation of the ratio of peak perfusion counts divided by plateau counts (P:PL). Deterioration of renal function was accompanied with a gradual loss of a peak and plateau pattern. For the evaluation of uptake in relation to perfusion pattern, we graded the renogram curves into four based on the presence of a peak and plateau pattern and the presence of an uptake peak. RESULTS: In patients with CAN, the mean P:PL was significantly lower than that of the control group. The serial changes in successive grades of CAN in respect to uptake-perfusion pattern was a gradual loss of peak and plateau pattern followed by a decline in uptake. In recipients with high-grade CAN, an uptake peak was absent. CONCLUSIONS: Evaluation of Tc-99m DTPA time-activity curves revealed a progressive change in perfusion-uptake pattern in patients with CAN. According to our results, deterioration of perfusion preceded the decline in uptake. Serial renogram changes are thought to reflect initial hypoperfusion followed by increased intraglomerular pressure and finally glomerulosclerosis. These findings have implications for the pathophysiology and management of CAN.

Biopsy↗

A very unusual presentation of Niemann-Pick disease type B in an infant: similar findings to congenital lobar emphysema.

The main features of Niemann-Pick disease type B (NPD-B) are enlargement of the liver and spleen, and mild pulmonary involvement. Recurrent respiratory tract infection and progressive decline in pulmonary function are major contributors to morbidity and mortality in this patient group. Massive pulmonary involvement in early life is extremely rare. The most common finding on chest X-rays of NPD-B patients is reticular or nodular infiltration of the lungs. This article describes a very rare presentation of NPD-B in an infant who had suffered recurrent respiratory tract infections. Massive emphysema and marked infiltrative parenchymal changes (infiltration of the parenchyma) were initially attributed to congenital lobar emphysema and its compressive effects. However, NPD was suspected when a lung biopsy showed foamy cells and sea-blue histiocytes were detected in a bone marrow biopsy. The definitive diagnosis was established with an enzyme study for sphingomyelinase.

Diagnosis, Differential↗

Primary ovarian leiomyosarcoma: a case report.

Primary ovarian leiomyosarcomas are extremely rare tumors that comprise less than 0.1% of all ovarian malignancies. We present a case of 62-year-old postmenopausal woman with a slightly enlarged right ovary and a Color Doppler sonography resistance index (RI) measuring 0.54. The patient, after being managed with surgery alone, is alive after 14 months without any evidence of disease. This is an unusual case in that primary ovarian leiomyosarcoma was diagnosed in the setting of a slightly enlarged irregular postmenopausal ovary with a concomitant intermediate RI value on color flow Doppler evaluation. A high index of suspicion may help prevent delay in the diagnosis of this rare neoplasm.

Diagnosis, Differential↗

Pelvic retroperitoneal paraganglioma mimicking an ovarian mass.

A 75-year-old hypertensive woman was referred with ultrasound findings of a 40 x 35 mm semi-solid right adnexal mass and right hydroureteronephrosis. She complained of headache and right-sided back pain. Computed tomography demonstrated a cystic adnexal mass that did not appear to originate from the right ovary and grade 2 hydroureteronephrosis. Magnetic resonance imaging indicated that the mass originated from the right ovary. Tumor markers were in the normal range. Exploratory laparotomy was performed to determine the origin of the lesion, and revealed a retroperitoneal mass obstructing the right ureter. The mass was completely removed and and the histopathologic diagnosis was paraganglioma.

Aged↗

The value of expanded polytetrafluoroethylene in preventing early re-ossification after craniosynostosis surgery: an experimental animal study in the rat.

BACKGROUND: Early re-ossification at the suturectomy site after craniosynostosis surgery remains an important problem. Many surgical methods have been used to address this, including placement of various types of absorbable and non-absorbable material between the bone edges at the site. This experimental study investigated the value of expanded polytetrafluoroethylene (ePTFE) membrane as a barrier to calvarial reclosure after craniosynostosis surgery in rats. METHOD: Thirty-five 2-week-old Sprague-Dawley rats were divided into two groups. In Group A (n = 17), ePTFE membranes were placed in the defect formed by a left coronal suturectomy. The Group B rats (n = 18) underwent left coronal suturectomy only. Animals were sacrificed at 1, 2 and 4 months postoperatively. In each case, the skull was removed and the operative site was examined for fibrosis, new bone formation, bone bridging, neovascularization and inflammatory response. FINDINGS: The two groups were similar with respect to neovascularization and new bone formation. By the end of the fourth postoperative month, 50% of the Group B specimens showed fibrosis and 50% showed bridging between the bone edges at the suturectomy site. In contrast, at the same stage in Group A, only 16.6% of the specimens exhibited a small amount of fibrosis, and none showed bone bridging between the edges. INTERPRETATION: Expanded PTFE is one of the most inert materials used in surgery. The study showed that inserting ePTFE membrane as a barrier between the bone edges at the suturectomy site prevents early re-ossification after craniosynostosis surgery in rats.

Animals↗

Acute myeloid leukemia 4 years after Kaposi's sarcoma in a renal transplant recipient.

BACKGROUND: Leukemia is a well-known complication of cancer therapy, but development of acute myeloid leukemia (AML) after renal transplantation is rare. Immunosuppressive therapy for organ transplant recipients is complicated by high rates of malignant disease, one condition being Kaposi's sarcoma (KS). CASE REPORT: A 22-year-old woman developed KS 1 year after renal transplantation, and then developed AML another 4 years later. When KS was diagnosed it was already in extensive stage, and she received ABV combination chemotherapy with doxorubicin plus bleomycin plus vincristine intravenously (i.v.) once daily every 2 weeks. She entered remission but the KS relapsed and 8 cycles of i.v. etoposide monotherapy were given and she re-entered remission. 19 months later, the patient was admitted to hospital with severe malaise, leukocytosis, thrombocytopenia, and anemia. The diagnosis was AML (FABM4). The patient received induction chemotherapy consisting of cytarabine and idarubicin. After completion of this induction therapy she developed neutropenic infection, dyspnea and confusion. Her condition deteriorated rapidly after that, and she died. CONCLUSION: KS is one of the most common malignancies in renal allograft recipients, whereas AML is a less frequent problem. To our knowledge, this is the first published case of these two different malignancies developing after renal transplantation. The pathogenesis of the AML is discussed.

Adult↗