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Öğe A 12 months course of interferon and lamivudine combination therapy versus interferon monotherapy for untreated chronic hepatitis B infection(Elsevier Science Bv, 2002) Yalcin, K; Yildiz, F; Degertekin, H; Celik, Y[Abstract Not Available]Öğe A 12-month course of combination therapy with interferon-alfa and lamivudine in patients with chronic hepatitis delta virus: A single-center, prospective, open-label, uncontrolled study(Excerpta Medica Inc, 2002) Yalcin, K; Degertekin, H; Yildiz, F; Akkus, ZBackground: Chronic hepatitis delta virus (HDV) is a severe and rapidly progressive liver disease for which no therapy has been proved to be effective. Objective: The aim of this study was to investigate the efficacy and tolerability of long-term therapy with a combination of recombinant interferon (IFN)-alfa. and lamivudine. Methods: In this single-center, prospective, open-label, uncontrolled study, patients aged 18 to 60 years with chronic HDV were eligible. Patients were treated with a combination of 10 million units of IFN-alfa-2b subcutaneously 3 times weekly and lamivudine 100 mg once daily for 12 months. The primary outcome measures were biochemical and histologic response at the end of treatment and at least 12 months thereafter. Results: Twelve patients (10 men, 2 women; mean age, 33.9 years [range, 19-49 years]) were enrolled (6 treatment-naive patients, 6 previously treated patients). Normalization or decrease of >50% from baseline in serum alanine aminotransferase (ALT) level occurred in 8 (66.7%) of 12 patients at month 12 of treatment. Of the 12 patients, 10 (83.3%) completed the trial; 1 (8.3%) was withdrawn because of severe leukopenia. and 1 (8.3%) was lost to follow-up. Relapses occurred in 5 of 8 (63.3%) initial responders shortly after the cessation of therapy. In 3 (25%) patients whose ALT levels became normal at the end of the therapy, the complete biochemical responses persisted for up to 3 years (mean, 31 months). The treatment was associated with a marked improvement in histologic activity. Conclusions: In this study, combination therapy with IFN-alfa and lamivudine was well tolerated and reduced hepatic inflammation was found. Further controlled trials are needed to show possible beneficial effects of this model of therapy and to determine the optimal dose and duration of therapy for chronic HDV.Öğe Comparison of 12-month courses of interferon-?-2b-lamivudine combination therapy and interferon-?-2b monotherapy among patients with untreated chronic hepatitis B(Oxford Univ Press Inc, 2003) Yalcin, K; Degertekin, H; Yildiz, F; Celik, YWe compared the use of prolonged synchronous combination therapy with interferon (IFN)-alpha-2b and lamivudine with the use of IFN-alpha-2b monotherapy in patients with untreated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B virus (HBV) infection. Thirty-three patients received therapy with lamivudine (100 mg daily) and IFN-alpha-2b (10 million U 3 times per week) for 12 months; 16 patients received IFN-alpha-2b alone (10 million U 3 times per week for 12 months). The primary end point was sustained suppression of HBV DNA and HBeAg seroconversion, which was observed in 15 (45%) of 33 patients treated with combination therapy and in 3 (19%) of 16 patients treated with monotherapy (P = .133). Both therapeutic regimens were well tolerated. Combination therapy increased the rate of sustained suppression of HBeAg and resulted in significant improvement in Knodell histologic activity index scores, compared with monotherapy. However, there was no significant difference in rates of sustained suppression between the 2 groups at the end of follow-up.Öğe Effects of intravitreal ropivacaine on retinal thickness and integrity in the guinea pig(Excerpta Medica Inc, 2005) Olmez, G; Cakmak, SS; Soker, SI; Nergiz, Y; Yildiz, FBackground: Retrobulbar anesthesia is widely used for ocular surgery. Ocular complications are possible when retrobulbar anesthesia is accidentally injected intravitreally. Objective: The aim of this study was to determine the relative retinal toxicities of ropivacaine hydrochloride, a local anesthetic, using various concentrations in guinea pigs. Methods: This randomized, investigator-masked, experimental study was conducted at the Department of Anesthesiology, Dicle University, Diyarbakir, Turkey. The right eyes of 18 guinea pigs were assigned to I of 3 treatment groups: 1%, 0.75%, or 0.5% ropivacaine. The right eye of each animal was injected intravitreally with 0.1 mL of 1%, 0.75%, or 0.5% ropivacaine. The left eye of each animal was injected with a balanced saline solution (control). The guinea pigs were euthanized 7 days after injection, and the retinal structures were examined using light microscopy. The total thickness of each retina was measured using an ocular micrometer. Results: No histologic abnormalities were observed in the control eyes. Retinal damage of most of the retinal section was seen in the eyes receiving study drug. The eyes injected with 0.5% ropivacaine had a generally intact appearance, with the exception of some atrophy and disorganization. Overall, the eyes injected with 1% ropivacaine had significantly more extensive retinal thinning compared with the eyes injected with 0.75% or 0.5% ropivacaine (both, P < 0.01). In the eyes injected with 0.75% or 1% ropivacaine, disorganization of the structure of the retinal layers and atrophy were noted on histopathology. The mean total thicknesses of the retina were significantly less in all ropivacaine-treated eyes compared with that in the controls (P < 0.001). Conclusions: In this small experimental study, ropivacaine had concentration dependent toxic effects on guinea pig retinas.Öğe Markers of disease activity in chronic hepatitis B virus infection(Canadian Medical Association, 2003) Yalcin, K; Degertekin, H; Yildiz, F; Celik, YBackground: Assessment of disease activity is important in the management of chronic hepatitis B virus (HBV) infection. Our objective was to study the correlation between serum HBV DNA levels and HBV e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, histologic activity, age and sex in patients who had chronic HBV, with emphasis on those who were HBeAg negative with high replication but had normal or below-normal liver enzyme levels and mild liver disease. Method: At our university-affiliated tertiary care medical centre in Turkey, we studied prospectively 179 consecutive patients who were long-term hepatitis B surface antigen carriers. These patients were first separated into 2 groups according to HBeAg positivity and then subdivided into 4 groups according to the presence of HBV DNA, HBeAg status and ALT levels. The clinical, virologic and histologic differences in these patients were evaluated with respect to the HBeAg status. Results: Of the 179 patients, 120 (67%) were HBeAg positive and 59 (33%) were HBeAg negative. The mean (and standard deviation) age in the former group was 24.8 (7.60) and in the latter group was 32.2 (11.2) years (p < 0.001). HBeAg-negative patients had significantly more severe liver disease, more male predominance and lower serum HBV DNA levels than HBeAg-positive patients (p < 0.05). HBeAg status had a close correlation with age. There was a significant correlation between age and serum HBV DNA levels but not between HBV DNA levels and disease activity in study groups. We found that some of anti-HBe-positive patients had below-normal ALT levels with minimal or absent histologic changes despite high viral replication. Conclusions: Monitoring of ALT is of value in assessing hepatocellular damage in patients with chronic hepatitis B virus infection. HBeAg-negative patients with elevated ALT levels and some with normal ALT levels should be considered highly infectious in the course of chronic HBV infection.Öğe N-acetylcysteine reduces lung reperfusion injury after deep hypothermia and total circulatory arrest(Wiley, 2004) Çakir, Ö; Oruc, A; Kaya, S; Eren, N; Yildiz, F; Erdinc, LObjective: We hypothesized that the use of N-acetylcysteine would ameliorate the lung reper-fusion injury observed after deep hypothermia and total circulatory arrest (DHTSA). Methods: Experiments were carried out on 12 adult mongrel dogs of either sex weighing 25 to 30 kg. The animals were randomly divided into two groups of six animals each. All animals were cooled to an esophageal temperature of 15 degreesC during 30 minutes and underwent 60 minutes of DHTSA, followed by the reinstitution of cardiopulmonary bypass (CPB) and rewarming. Before rewarming, while 100 mL physiologic saline solution was added into the pump in group 1, 50 mg/kg N-acetylcysteine(NAC) was given in group II. Heart rate, mean arterial pressure, pulmonar arterial pressure, left atrial pressure, central venous pressure, and cardiac output were recorded. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes (PMNs) count, lung tissue samples were taken before CPB and after weaning CPB. In addition, alveolar-arterial oxygen difference (AaDO(2))for tissue oxygenation was calculated by obtaining arterial blood gas samples. Dynamic lung compliance (DLC) was measured before CPB and after CPB. Results: MDA levels before CPB of 44.2 +/- 3.9 nmol/g tissue rose to 76.6 +/- 5.6 nmol/g tissue after weaning CPB in group I (p = 0.004). In group II also, the MDA levels increased from 43.5 +/- 4.2 to 57.4 +/- 5.6 nmol MDA/g tissue after weaning CPB (p = 0.006). The MDA increase in group 11 after CPB was found to be significantly lower than in group I (p = 0.006). The wet-to-dry lung weight ratio in the NAC group was 5.1 +/- 0.2, significantly less than in the control group (5.9 +/- 0.3), (p = 0.004). AaDO(2) significantly increased in the group I and II (p = 0.002 and p = 0.002, respectively); this elevation in group I was significant than in group II (p = 0.044). In histopathological examination, it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups (p < 0.001). The increase in group I was significantly larger than group II (p < 0.001). Conclusions: Results represented in our study indicate that addition of NAC into the pump after DHTSA can reduce lung reperfusion injury.Öğe A severe hepatitis flare in an HBV-HCV coinfected patient during combination therapy with ?-interferon and ribavirin(Springer-Verlag Tokyo, 2003) Yalcin, K; Degertekin, H; Yildiz, F; Kilinc, NWe report a reactivation of hepatitis B virus infection and a severe hepatitis flare in a patient with chronic hepatitis due to dual infection with hepatitis B and C viruses during combination therapy with alpha-interferon and ribavirin. Pretreatment, HCV was the dominant virus, with detectable serum HCV-RNA but undetectable HBV-DNA. The patient responded to therapy, with the disappearance of HCV-RNA and normalization of serum alanine aminotransferase (ALT) at months 1 and 6. In the seventh month of therapy, an ALT flare was observed, and serum HBV-DNA became detectable. The patient had a severe hepatitis flare leading to impending hepatic failure. Treatment was discontinued and the patient had marked clinical and biochemical improvement and recovered with normalization of liver function test results within 1 month. Two months later, serum HBV-DNA was again undetectable, both by hybridization and polymerase chain reaction (PCR) assays. The patient had a rapid progression to cirrhosis in a year. At month 24, 17 months after the end of therapy, serum HCV-RNA reappeared, with a level of 2.4 X 10(5) copies/ml. In conclusion, severe HBV reactivation may occur during interferon plus ribavirin therapy in patients with chronic hepatitis C who are also hepatitis B surface antigen (HBsAg)-positive, and thus more careful monitoring than usual should be considered. Longterm follow-up is recommended, because very late HCV relapses may occur in coinfected patients. These data exemplify the complexity of viral dominance in patients infected with multiple hepatitis viruses, and this has significant importance for treatment decisions. Lamivudine may be administered early in HCV-RNA/HBsAg-positive patients who ate at high risk of liver failure once reactivation of HBV occurs during interferon therapy.
