[Investigation of oxidative stress and antioxidant defense in patients with hepatitis B virus infection and the effect of interferon-alpha plus lamivudine combination therapy on oxidative stress]. / Hepatit B virus enfeksiyonlu hastalarda oksidatif stres ve antioksidan kapasitenin arastirilmasi ve interferon-alpha-lamivudin kombinasyon tedavisinin oksidatif stres üzerine etkisi.

The aim of our study is to determine the role of oxidative stress on hepatic damage in patients with acute and chronic hepatitis B virus (HBV) infection and the efficacy of antioxidant-enzyme system against oxidative stress. Furthermore, the effect of interferon-alpha (IFN-alpha) plus lamivudine therapy on oxidative stress was also investigated. Nineteen patients with acute hepatitis B virus (AHBV) infection, 17 patients with chronic hepatitis B virus (CHBV) infection, 24 inactive HBsAg carriers and 21 healthy controls were included in the study. In control and patient groups, serum alanine-aminotransferase (ALT) and aspartate aminotransferase (AST) levels, erythrocyte malondialdehyde (MDA) levels, erythrocyte superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) activities were measured. In CHBV group, after IFN-alpha plus lamivudine therapy for 6 months, these parameters were measured again. In all patient groups erythrocyte MDA levels were detected higher than control group (p < 0.05). Activity of CuZn-SOD was found to be the highest in AHBV (p < 0.05), and the lowest before the treatment in CHBV group (p < 0.05) compared with other groups. Activity of GSH-Px was found to be the highest in AHBV compared with inactive HBsAg carriers (p < 0.05) and CHBV group before treatment (p < 0.05). Activity of GSH-Px was found to be the lowest in CHBV group before treatment compared with other groups (p < 0.05). In CHBV group there was a significant decrease of MDA levels after treatment (p < 0.05) while there was a significant increase in activity of CuZn-SOD and GSH-Px compared with pretreatment levels (p < 0.05). A significant positive correlation was determined between MDA values and serum ALT levels, before and after the treatment (p < 0.05). Detection of the increase of MDA levels which is a product of lipid peroxidation in all patient groups, indicates that the oxidative stress is increased in HBV infection. Correlation between the levels of erythrocyte MDA levels and serum ALT levels supports the hypothesis concerning the role of oxidative stress in pathogenesis of HBV infection. Insufficiency of antioxidant capacity in CHBV and inactive HBsAg carrier groups may lead to progression of disease and results in fibrosis. Treatment with IFN-alpha plus lamivudine causes a decrease in products of lipid peroxidation and shows antioxidant activity via increasing the antioxidant enzymes. These data suggest that the addition of antioxidant agents to IFN-alpha and lamivudin combination therapy may be useful in CHBV treatment. Further in-vitro and in-vivo studies are required to enlighten the role of antioxidants on HBV disease progression and treatment.

The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.

OBJECTIVE: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. METHODS: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiary-care hospitals was conducted. RESULTS: The mean age of the patients was 42+/-17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37+/-23 days) was significantly longer compared to the patients with ID (25+/-12 days) (p=0.007). In patients with MD, the mean duration of fever (51+/-35 days) was longer compared to patients with ID (37+/-38 days) (p=0.052). CONCLUSIONS: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies.

Saccharomyces boulardii and infection due to Giardia lamblia.

Therapy with metronidazole is the recommended option in giardiasis. However, some clinical trial reports suggest the appearance of drug resistance to explain therapeutic failure. Several investigations have been carried out on the effect of probiotic microorganisms for preventing or treating gastrointestinal diseases, but little is known about their efficacy against protozoal infections. The principal objective of our study was to evaluate the efficacy of Saccharomyces boulardii against Giardia lamblia infections. A double-blind, placebo-controlled study was carried out on adult patients with giardiasis. Group 1 (30 patients) included metronidazole 750 mg 3 times daily along with S. boulardii capsules (250 mg b.i.d. orally) for 10 d while group 2 (35 patients) was treated with metronidazole 750 mg 3 times daily and with empty capsules as placebo for 10 d. Patients were re-examined at 2 and 4 weeks after treatment, and stool examinations were performed. At week 2, G. lamblia cysts were detected in 6 cases (17.1%) of group 2 and none in group 1. At the end of the fourth week, presence of the cysts continued in the same 6 cases in group 2 (control group). These findings indicated that S. boulardii may be effective in treating giardiasis when combined with metronidazole therapy.

Prophylactic Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea: a prospective study.

BACKGROUND: Interest to probiotics for the prevention and treatment of antibiotic-associated diarrhea is increasing gradually. The most promising seems to be Saccharomyces boulardii . Using a double-blind controlled study, we investigated the preventive effect of S. boulardii on the development of antibiotic-associated diarrhea in patients under antibiotherapy but not requiring intensive care therapy. MATERIAL/METHODS: All the patients were hospitalized at the Gulhane Military Medical Academy, Department of Infectious Diseases and Clinical Microbiology. S. boulardii was given twice daily during the course of antibiotic therapy and application was initiated in all patients as late as after 48 hours of antibiotic therapy. A total of 151 patients completed the study. RESULTS: The antibiotic-associated diarrhea development ratio in placebo group was 9% (7/78) and in the study group 1.4% (1/73) (p < 0.05). Stool samples from the patients with antibiotic-associated diarrhea were stored at -70 degrees C and Clostiridium difficile toxin A assay was performed using Enzyme Immune Assay as late as in seven days. C. difficile toxin A assay yielded positive results in two (2/7) stool samples from the patients with antibiotic-associated diarrhea in the placebo group and a negative result in the only patient who developed antibiotic-associated diarrhea in the study group. CONCLUSIONS: The results implied that prophylactic use of Saccharomyces boulardii resulted in reduced, with no serious side effects, antibiotic-associated diarrhea in hospitalized patients.

The effects of topical ketorolac and indomethacin on measles conjunctivitis: randomized controlled trial.

PURPOSE: To compare the effect of topical ketorolac and indomethacin on measles conjunctivitis. DESIGN: Prospective double-masked placebo-controlled randomized trial. METHODS: Sixty-two patients with severe measles conjunctivitis were included in this study. All patients were hospitalized and randomly assigned to receive ketorolac 0.5% or indomethacin 0.1% in the right eye and artificial tears in the left eye. Conjunctival hyperemia, burning sensations, foreign-body sensations, and photophobia scores were conducted at baseline and at days seven and 14. A satisfaction score was evaluated at the end of the study. RESULTS: The conjunctival injection score of the control eyes was significantly higher than those of the ketorolac- and indomethacin-treated eyes at day seven (P < .05). The conjunctival injection score of the ketorolac-treated eyes was lower than that of the indomethacin-treated eyes at days seven and 14, but this did not reach statistical significance. There was no significant difference in the burning and foreign-body sensations and in the photophobia scores among the study eyes at baseline, day seven, and day 14 (P > .05). There was no significant difference in the satisfaction score among the study eyes at the end of the study (P > .05). CONCLUSIONS: In patients with measles during the first two weeks of infection, ketorolac and indomethacin were more effective than artificial tears in decreasing conjunctival hyperemia, but burning sensations, foreign-body sensations, and photophobia were unaffected.

Rapid and quantitative detection of Crimean-Congo hemorrhagic fever virus by one-step real-time reverse transcriptase-PCR.

In this article, the development of a new TaqMan-based one-step real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay for detection and quantification of Crimean-Congo hemorrhagic fever virus (CCHFV) RNA is described. Selected oligos targeting the highly conserved S region of CCHFV were designed by using our oligo design and analysis software, Oligoware 1.0. None of the primer sequences showed genomic cross-reactivity with other viruses or cells in a BLAST (NCBI) search analysis. The sensitivity and specificity of the primers and the probe were tested using 18 serum samples from patients from East Anatolian who were suspected of having CCHFV, including 2 samples that had already been confirmed to be positive for CCHFV. Among the 16 previously unconfirmed samples, 5 were positive by TaqMan-based one-step real-time RT-PCR and 1 was positive by non-nested RT-PCR, and these results were confirmed with DNA sequencing analysis. The 2 previously confirmed CCHFV RNA samples were also positive by both TaqMan-based one-step real-time RT-PCR and non-nested RT-PCR tests. To ensure the quantitative reproducibility of TaqMan-based one-step real-time RT-PCR, the procedure was repeated several times and the same results were obtained (SD = 0.84 [maximum value]). The developed assay was able to sensitively quantify the concentration of CCHFV RNA, which ranged from 10(2) to 10(7) copies/ml per reaction, using plasmid standards generated from the CCHFV RNA (correlation coefficiency = 0.989). The results of the one-step real-time RT-PCR assay were more sensitive than those of the non-nested RT-PCR assay. It can be concluded that our one-step real-time RT-PCR assay is a reliable, reproducible, specific, sensitive and simple tool for the detection and quantification of CCHFV.

Effect of climate on the bacteriology of chronic suppurative otitis media.

OBJECTIVES: We evaluated the correlation between the microbial content of chronic suppurative otitis media (CSOM) and regional climatic parameters. METHODS: We assessed the interrelations between monthly mean records of temperature, maximum temperature, atmospheric pressure, and humidity and the aerobic microbial flora in CSOM. RESULTS: Forty-three bacteria of Enterobacteriaceae, 67 staphylococcal spp, 51 Pseudomonas aeruginosa, 9 Streptococcus pneumoniae, 1 alpha-hemolytic Streptococcus, 1 Enterococcus sp, and 2 Edwardsiella tarda strains were recovered from 173 patients with CSOM. There was a good relationship between enteric bacteria and monthly mean temperature (r = 0.501) and significant colonization rates due to increasing monthly mean temperature (p = .040) and monthly mean maximum temperature values (p = .048). CONCLUSIONS: When the weather warmed, the frequency of isolation of enteric bacteria increased significantly. Temperature changes may affect the enteric bacterial colonization of CSOM.

Therapeutic options for pneumococcal pneumonia in Turkey.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Streptococcus pneumoniae continues to be the most important causative agent in CAP. OBJECTIVE: This article reviews options for the empiric treatment of pneumococcal pneumonia in Turkey based on local epidemiologic data. METHODS: This was a retrospective review of studies evaluating antimicrobial susceptibility patterns among clinical isolates of S pneumoniae in Turkey from 2000 onward. Relevant studies were identified through literature searches of both Turkish (Ulakbim and Pleksus) and international (MEDLINE) databases using the search terms S pneumoniae and Turkey. Only antibiotics likely to be used in pneumococcal pneumonia were evaluated. The minimum concentration required to inhibit 90% of isolates (MIC(90)) for each antibiotic was obtained by averaging all reported values to arrive at a single value for the entire country. RESULTS: The MIC(90) for penicillin was 1 g/mL; among all isolates of S pneumoniae, 6.4% were penicillin resistant and 30.9% showed intermediate susceptibility. The MIC(90)s and overall rates of resistance (combined intermediate susceptibility and resistance) for the other antibiotics studied were as follows: cefaclor, 4 microg/mL (26.3%); cefuroxime, 2 microg/mL (15.4%); ceftriaxone, 0.25 microg/mL (0.75%); imipenem, 0.06 microg/mL (0%); erythromycin, 2 microg/mL (13.9%); clarithromycin, 2 microg/mL (13.7%); azithromycin, 2 microg/mL (13.8%); telithromycin, 0.06 microg/mL (no published breakpoints); trimethoprim-sulfamethoxazole, 4 microg/mL (63.8%); tetracycline, 16 microg/mL (24.6%); ciprofloxacin, 2 microg/mL (no published breakpoints); ofloxacin, 2 microg/mL (4%); levofloxacin, 1 microg/mL (0%); gemifloxacin, 0.06 microg/mL (no published breakpoints); and moxifloxacin, 0.06 microg/mL (0%). Penicillin G, at standard parenteral doses, has been shown to achieve concentrations above the MIC for >40% to 100% of the dosing interval, depending on the MIC of the isolate. Based on pharmacodynamic studies, the MIC(90) for penicillin in Turkey should easily be exceeded with the use of penicillin G 3 mU QID. In vitro, susceptibility is generally greater to amoxicillin than to penicillin, with average amoxicillin MIC values approximately 1 dilution lower than those for penicillin. Amoxicillin's better pharmacodynamic/pharmacokinetic properties relative to penicillin make it a reasonable option for the treatment of CAP. In pharmacodynamic studies, amoxicillin 1 g TID achieved and maintained serum concentrations of 2 to 4 microg/mL for at least 40% of the dosing interval. A new formulation of amoxicillin/clavulanate given 2000/125 mg BID is expected to eradicate isolates of S pneumoniae at an amoxicillin MIC < or = 4 microg/mL. CONCLUSIONS: Based on data from Turkish surveillance studies performed from 2000 onward, high-dose parenteral penicillin G and parenteral/oral amoxicillin may be initial choices for the empiric treatment of uncomplicated pneumococcal pneumonia in Turkey. If these agents cannot be used for any reason, other options include parenteral cefuroxime, ceftriaxone, cefotaxime, newer quinolones, macrolides, and telithromycin. Due to elevated rates of resistance in Turkey, trimethoprim-sulfamethoxazole and tetracyclines are not recommended for empiric use in these infections.

The effect of the doxycycline-rifampicin and levamisole combination on lymphocyte subgroups and functions of phagocytic cells in patients with chronic brucellosis.

BACKGROUND: Brucellosis is one of the important health problems for both humans and animals in Turkey since agriculture and stock raising appears to be the most important means of subsistence. Investigations on the pathogenesis of brucellosis reveal that the etiologic agent can survive in phagocytic cells, and cell-mediated immunity plays an important role in immunity against bacteria. METHODS: In this study, we investigated whether supplementation of levamisole, a well-known antihelminthic agent with immune-stimulating activity to conventional antibiotic therapy, would improve the anergy against Brucella. RESULTS: The results of our study reveal that a 6-week course of levamisole as a supplement to conventional antibiotic therapy in chronic brucellosis is not superior to conventional antibiotic treatment alone with respect to lymphocyte subgroup ratios and phagocytic function. CONCLUSION: In chronic brucellosis, levamisole administered as a supplement concomitantly with conventional antibiotic therapy has no immunostimulating effect on the basis of the lymphocyte subgroups ratios measured and the ability of phagocytosis in the present study. Further large clinical and laboratory trials are necessary to investigate the immunological and physiological effects of levamisole on T(H1) subtypes and cytokine secretion.

Classification of Giardia duodenalis parasites in Turkey into groups A and B using restriction fragment length polymorphism.

PCR-RFLP (restriction fragment length polymorphism) analysis was used to determine the relation of Giardia duodenalis Groups A and B. Of these, 17 (85%) were found as Group A in symptomatic cases; 22 (92%) were Group B in asymptomatic cases by using PCR-RFLP (p < 0.001). Interestingly, 5 (83%) were Group A in examination of endoscopy aspirates of symptomatic cases, as 5 (83%) were Group B in asymptomatic cases.

Neisseria meningitidis W135, Turkey.

We describe the first case of Neisseria meningitidis W135 meningitis in Turkey. The strain was genotypically unrelated to the clone (W)ET-37, isolated from Hajj pilgrims in 2000.

Symptomatic intestinal amoebiasis and climatic parameters.

Symptomatic intestinal amoebiasis is an important problem, especially in the developing world. The relationships between climatic parameters and amoebic dysentery cases were evaluated in this study. Climatic data were obtained from the local meteorological department and the diagnosis of amoebic dysentery was established by clinical and laboratory investigation. Monthly mean temperature (r = 0.755, p = 0.005), monthly mean maximum temperature (r = 0.711, p = 0.01), monthly mean temperature at 100 cm underground (r = 0.818, p = 0.001) and monthly mean humidity values (r = -0.656, p = 0.02) correlated significantly with symptomatic disease. Although inverse relationships were found for humidity and atmospheric pressure, the monthly mean atmospheric pressure (r = -0.084) did not seem to have a significant effect on intestinal amoebiasis (p = 0.80). Thus, when the weather warmed up, the frequency of symptomatic intestinal amoebiasis increased significantly. To improve the ability to predict disease trends, it seems logical to assess the independent and interactive effects of climatic parameters on disease impact.

Minimal change disease in a patient receiving IFN-alpha therapy for chronic hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic syndromes. The principal types of renal disorders associated with chronic HCV infection are cryoglobulinemia or noncryoglobulinemic membranoproliferative glomerulonephritis (MPGN). Interferon-alpha (IFN-alpha) may precipitate or exacerbate the occurrence of MPGN. Our patient was a 32-year-old man who tested positive for HCV in July 1997. The patient was treated with IFN-alpha in another medical center for 6 months because his liver biopsy showed chronic active hepatitis. In December 1998, he applied to our clinic for a follow-up examination. The level of aspartate aminotransferase (AST) was 44 U/L, and that of alanine aminotransferase (ALT) was 69 U/L. HCV RNA was positive in serum, and chronic HCV infection was detected by liver biopsy. IFN-alpha therapy (5 million U/day) was administered for 6 months longer. In May 1999, the patient came to our polyclinic with edema of the feet and legs. We detected proteinuria, serum cholesterol of 269 mg/dl, AST of 50 U/L, ALT of 41 U/L, serum total protein of 3.4 g/dl, serum albumin of 1.2 g/dl, positive cryoglobulin, and urine protein of 9.84 g/day. Cryoglobulinemic MPGN was suspected and kidney biopsy was performed, resulting in a diagnosis of minimal change disease (MCD).