Osman Özcebe

Screening of tissue transglutaminase antibody in healthy blood donors for celiac disease screening in the Turkish population.

Celiac disease (CD) is a disease having the characteristic pathology of the mucosa of the small intestine. The prevalence of CD in the Turkish population has not been investigated previously. The present study was designed to determine the prevalence of CD in healthy blood donors. Serum samples of 2000 healthy blood donors presenting to Hacettepe University Faculty of Medicine Hospital Blood Bank were tested for tissue transglutaminase (tTG) IgA and IgG antibodies with enzyme-linked immunosorbent assay (ELISA; Euroimmune, Germany). The histopathological findings for the cases with positive serology were evaluated. The distribution of sex was 95.7% male, and 4.3% female. The mean age was 33±9. Among 2000 donors, 23 (1.15%) were positive for tTG IgA antibody and 3 (0.15%) were positive for tTG IgG antibody. None of the samples was positive for both antibodies. Serum total IgA was measured in two cases with only tTG IgG positivity and was found to be low in one case. Twelve subjects positive for tTG agreed to endoscopy and biopsy. Histopathological examination revealed changes classified as Marsh III–II in one, Marsh II in two, Marsh I in seven, and Marsh 0 in two donors. This was the first study conducted to determine the prevalence of tTG positivity in the Turkish population. The tTG antibody positivity prevalence in healthy blood donors was as high as 1.3%. This study shows that the prevalence of CD in the Turkish population is relatively high in comparison to that in the Western world.

Interferon alfa-2b, colchicine, and benzathine penicillin versus colchicine and benzathine penicillin in Behçet's disease: a randomised trial

BACKGROUND Sight-threatening eye involvement is a serious complication of Behçets disease. Extraocular complications such as arthritis, vascular occlusive disorders, mucocutaneous lesions, and central-nervous-system disease may lead to morbidity and even death. We designed a prospective study in newly diagnosed patients without previous eye disease to assess whether prevention of eye involvement and extraocular manifestations, and preservation of visual acuity are possible with combination treatments with and without interferon alfa-2b. METHODS Patients were randomly assigned 3 million units interferon alfa-2b subcutaneously every other day for the first 6 months plus 1.5 mg colchicine orally daily and 1.2 million units benzathine penicillin intramuscularly every 3 weeks (n=67), or colchicine and benzathine penicillin alone (n=68). The primary endpoint was visual-acuity loss. Analysis was by intention to treat. FINDINGS Significantly fewer patients who were treated with interferon had eye involvement than did patients who did not receive interferon (eight vs 27, relative risk 0.21 [95% CI 0.09-0.50], p<0.001). Ocular attack rate was 0.2 (SD 0.62) per year with interferon therapy and 1.02 (1.13) without interferon therapy (p=0.0001). Visual-acuity loss was significantly lower among patients treated with interferon than in those without interferon (two vs 13, relative risk 0.13 [95% CI 0.03-0.60], p=0.003). Arthritis episodes, vascular events, and mucocutaneous lesions were also less frequent in patients treated with interferon than in those not receiving interferon. No serious side-effects were reported. INTERPRETATION Therapy with interferon alfa-2b, colchicine, and benzathine penicillin seems to be an effective regimen in Behçets disease for the prevention of recurrent eye attacks and extraocular complications, and for the protection of vision.

Transfusion-associated graft-versus-host disease in immunocompetent patients: case series and review of the literature

BACKGROUND: Transfusion‐associated graft‐versus‐host disease (TA‐GVHD) is a fatal complication of transfusion of blood products that usually affects immunocompromised patients. Articles reporting this condition in immunocompetent recipients are usually from countries that still have problems in irradiation of blood products.

Is elevated level of soluble endothelial protein C receptor a new risk factor for retinal vein occlusion

Background:  To evaluate the systemic and thrombophilic risk factors for retinal vein occlusion (RVO) and to determine whether the elevated level of soluble endothelial protein C receptor (sEPCR) is a risk factor for thrombosis.

Over-expression of angiotensin-converting enzyme (CD 143) on leukemic blasts as a clue for the activated local bone marrow RAS in AML

Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting hematopoiesis. Angiotensin II type 1a (AT1a) receptors are present on the CD34+ hematopoietic stem cells. Angiotensin II stimulates the proliferation of bone marrow and umbilical cord blood hematopoietic progenitors. There are preliminary data that local RAS might also be involved in leukemogenesis. ACE hyper-function may lead to the acceleration of negative hematopoietic regulator peptide, AcSDKP, metabolism, which in turn lowers its level in the bone marrow micro-environment, finally removing the anti-proliferative effect of AcSDKP on the hematopoietic cells and blasts. Renin expression could have a role on the leukemia development and angiotensin may act as an autocrine growth factor for acute myeloid leukemia (AML) cells. The aim of this study is to search ACE (CD 143) surface antigen by flow-cytometric analyses on the leukemic blast cells taken from the bone marrow of the patients with AML. Bone marrow aspiration materials and peripheral blood samples were obtained from 11 patients with AML (eight males, three females; aged 46 (range 26–67) years) and six patients with non-malignant hematological disorders (four males, two females; aged 56 (range 22–71) years). ACE (CD 143) surface antigen was shown to be over-expressed in leukemic myeloid blast cells. ACE is positively correlated with bone marrow blast count. Elucidation of the pathological activity of the local RAS-mediated regulation of the leukemogenesis is both pathobiologically and clinically important, since the angiotensin peptides represent a molecular target in the disease management.

Assessment of autonomic nervous system function in patients with Behcet' s disease by spectral analysis of heart rate variability.

The purpose of this study was to evaluate the autonomic nervous system (ANS) function in patients with Behçets disease by using power spectral analysis of heart rate variability (HRV). The study population consisted of 71 patients with Behçets disease, and 26 normal volunteers. HRV was measured by power spectral analysis in supine and standing position. In supine position, Behçets patients had increased low frequency component in absolute (LF) and normalized units (LF nU) but had lower values of high frequency component in absolute (HF) and normalized units (HF nU) than the controls (P < 0.05). In standing position, higher values were obtained in LF and LF nU but lower values of HF and HF nU in Behçets patients than controls (P < 0.05). LF/HF was significantly higher in patients both in supine (2.5 +/- 1.0 vs. 1.2 +/- 0.8, P = 0.001) and standing (21.9 +/- 7 vs. 1.8 +/- 0.3, P < 0.001) positions. Our data suggest that patients with Behçets disease may have asymptomatic ANS dysfunction, which is in the form of increased sympathetic and decreased parasympathetic modulation, and power spectral analysis of HRV is beneficial in assessing the ANS function.

Frequency of HFE mutations among Turkish blood donors according to transferrin saturation: genotype screening for hereditary hemochromatosis among voluntary blood donors in Turkey.

Background and Goals The C282Y and H63D mutations of HFE gene are associated with hereditary hemochomatosis (HH), the most common autosomal recessive disorder in European population. This is the first Turkish population study of, the prevalence of these mutations. Study 2677 healthy volunteer blood donors were screened by means of transferrin saturation (TS) with the cutoff value of 45. As study group, 86 donors with a TS 45 or higher and as control group 57 donors with TS less than 45 were tested for these mutations, ferritin, and alanin aminotransferase (ALT) levels. Results The mean age of donors were 33 ± 9 and 94.1% of them were male. The number of donors with TS 45 or higher was 265 (9.9%). C282Y mutation was not detected. The frequency of H63D mutation in the study, control and general groups were 27.32%, 21.05%, and 24.83%, respectively. As a result, the H63D mutation was present in 60 out of 143 participants in whom 49 were heterozygote (frequency of heterozygote allel 49/286 = 17.13%), 11 were homozygote (frequency of homozygote allel 22/286 = 7.69%). Serum ALT and TS were not affected from the type of H63D mutation. There was no difference in ferritin levels according to type of H63D mutations among 143 blood donors. Conclusion This study revealed the absence of C282Y mutation in our population. Although the frequency of H63D heterozygosity seems to be higher than the other population, the genetic screening for the HFE gene mutation is inadequate and the phenotypic screening with TS and ferritin seems to be preferable in Turkish population.

Perianal infections in patients with leukemia

PURPOSE: This study was performed to evaluate relations among neutrophil count (including its course), type of lesion, treatment, and prognosis in patients with leukemia and perianal infection. METHODS: Medical records of patients with acute and chronic leukemia who were followed during the last five years were reviewed retrospectively. RESULTS: The incidence of perianal infections was found to be 7.3 percent in 259 patients with acute leukemia. Only 1 of 108 patients with chronic leukemia suffered from this problem. Twenty percent of all patients with this complication died as a result of sepsis. Perianal abscess was the sole and obligatory indication for surgical treatment in our patients. There were ten patients in each treatment group. The operative group had better results (9 cures, 1 complicationvs. 3 cures, 7 complications). However, median neutrophil count at diagnosis was notably higher in the operative group 1,280/mm3vs. 96/mm3;P=0.075). Also, significantly more frequent abscess formations and, consequently, operative treatments were performed in patients with a period of normal neutrophil counts during the infection compared with continuously neutropenic patients (9 operative, 4 nonoperativevs. 1 operative, 6 nonoperative;P=0.057). Ten cures, three complicationsvs. two cures, five complications (3 mortalities) were present in patients with and without normal neutrophil counts, respectively (P=0.062). When only severely neutropenic patients were considered, four patients in the surgery group had normal neutrophil counts before or shortly after surgery. However, only two of eight patients with perianal cellulitis had normal counts during full-course infection (P=0.06). CONCLUSIONS: The course of the neutrophil count during infection was an important factor affecting the perianal lesion, and indirectly, choice of treatment and prognosis. A period of normal counts during infection usually led to well bordered and fluctuant lesions, and the prognosis was acceptable with operative treatment. However, continuously neutropenic patients developed nonfluctuating indurations. We found disappointing results with nonoperative treatment of such patients. In all studies, regarding treatment of perianal infections in neutropenic patients, the course of the neutrophil count and indications for surgery should be clarified to get reliable results.

Local umbilical cord blood renin–angiotensin system

Local bone marrow (BM) renin–angiotensin system (RAS) is an autocrine-paracrine system affecting normal and neoplastic hematopoiesis. Angiotensin II type 1a (AT1a) receptors are present on the CD34+ hematopoietic stem cells (HSC). Angiotensin II stimulates the proliferation and differentiation of the HSC populations through the activation of AT1 receptors on HSC. Umbilical cord blood (UCB) is a rich source of HSC. The existence of a complete local UCB RAS has not been previously investigated. In this study, local synthesis of the major RAS components, namely, angiotensin-converting enzyme (ACE), renin, and angiotensinogen, was identified by demonstrating their corresponding mRNAs using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in human UCB. Local RAS could regulate cellular growth in a variety of tissues including the BM. Major RAS peptides can exert significant effects on primitive pluripotential HSC populations. Further studies should focus on the interactions between possible autocrine, paracrine, endocrine, and intracrine actions of the local UCB RAS and growth, engraftment, differentiation, and plasticity functions of HSC of UCB origin.

Unchanged global fibrinolytic capacity despite increased factor VIIa activity in Behçet's disease: evidence of a prethrombotic state

Abstract.The aim of this study was to evaluate coagulation and fibrinolytic systems in Behçets disease (BD). Accordingly, various parameters of the coagulation and fibrinolytic systems were investigated in 39 patients with BD and 31 age- and sex-matched healthy volunteers as the control group. Seven of these patients with BD had histories of thrombotic complication. Three were found to have decreased protein S activity, and one patient had diminished protein C activity. Each of those patients had experienced a thromboembolic event. Activated protein C resistance was present in two patients, one of whom had had a thromboembolic episode. Activated FVII (FVIIa), fibrinogen, and cholesterol levels were significantly higher in patients with BD than in the control group. In the patient group, plasma FVIIa level was inversely correlated with age. Plasma global fibrinolytic capacity (GFC) did not differ between the patients and control group. No statistically significant difference was found in the GFC and FVIIa levels between patients with and without histories of thrombosis. Although the coagulation system was activated in vivo in patients with BD, there was no reactive activation in the fibrinolytic system to counteract the activated coagulation system. These findings suggest a relative hypofibrinolytic state in BD.