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This retrospective study examined the prognostic significance and treatment effect of promoter methylation of O6- methyl guanine methyl transferase (MGMT) and meth-ylation of CpG 1, CpG2, CpG3 and CpG4 in glioblastoma (GB) patients received postoperative radiotherapy (PORT), with or without adjuvant temozolomide (TMZ). One hundred patients with GB who received PORT with concomitant TMZ plus adjuvant TMZ or PORT alone, were included. The MGMT promoter methylation of CpG1, CpG2, CpG3 and CpG4 islands were examined. Overall, MGMT-methylation emerged as a significant prognostic factor for better overall survival (OS) and progression-free survival (PFS) [odds ratio (OR): 0.609, 95% confidence interval (95% CI): 0.395-0.939, p= 0.02; OR: 0.662,95% CI: 0.430-1019, p= 0.5, respectively]. The methylation of each CpG1, CpG2, CpG3 and CpG4 islands was found to have no significant effects on OS and the methylation of each CpGl, CpG2 and CpG4 islands had no significant effect on PFS (p <0.05 for all). On the other hand, the methylation of CpG3 had a positive prognostic effect on PFS (OR: 2.1, 95% CI: 0.99-4.67, p= 0.04). In the group that only received radiotherapy (RT), CpG1 and CpC3 methylations were found to have a positive prognostic significance in terms of PFS (OR: 266, 95% CI: 1.05-6.75, p-0.03 for CpG1; OR: 2.4, 95% CI: 1.01-5.92, p= 0.04 for CpG3). The MGMT promoter methylation represents an important biomarker for predicting response to therapy. Individual islands, particularly CpG3, deserves further investigation as a prognostic marker. Further studies need to be done with larger sample sizes to clarify the results.

Resistance of gram-negative aerobic bacteria to aminoglycoside antibiotics differs by region and country. It is known that 54% of gram-negative bacilli in Turkey are resistant to gentamicin, 32% to netilmicin, 35% to tobramycin, and only 0.9% to amikacin. Resistance to these antibiotics is generally caused by aminoglycoside-modifying enzymes. The resistance mechanisms of 300 aminoglycoside-resistant gram-negative bacteria were evaluated by determination of susceptibility to selected aminoglycosides. Comparison of strains isolated from community acquired infections and hospital acquired infections was made. Of the strains from community, 45.4% had an aminoglycoside resistance pattern indicative of 2''-adenyl-transferase [ANT(2'')]. This was found in 44.4% of the hospital isolates. In both groups the second common enzyme was the 3-acetyltransferase [AAC(3)-II], in 20.8% and 23.3% respectively. Overall, most strains had an aminoglycoside resistance pattern indicative of ANT(2''), followed by AAC(3)-II and AAC(3)-I. Among bacteria tested, AAC(3)-II was the most common enzyme in Pseudomonas aeruginosa. The results of this study suggest that local antibiotic prescribing patterns play an important role in regional resistance mechanisms.

Complement activation has been deemed responsible for the damaging effects of cardiopulmonary bypass (CPB) in patients undergoing open heart surgery. We studied C3, C4 and C-reactive protein (CRP) in 22 patients undergoing CPB. In Group 1 (11 patients), protamine was given intravenously and in Group 2 (11 patients), via the aortic root after CPB. Significant decreases were observed in C3 and C4 during CPB in both groups indicating complement activation primarily by the classic pathway. Protamine did not lead to further activation of the complement system. In both groups, C3 levels gradually returned toward baseline within 24 hours but C4 levels were still lower than baseline 24 hours postoperatively. CPB and protamine administration did not cause any significant changes in CRP levels, but CRP increased abruptly 24 hours after operation. Although activation of complement system during CPB is expected to invoke an acute phase response, we conclude that this period is not long enough to induce an increased production of CRP in response to tissue injury or inflammation.

Diarrhoeal diseases are still an important health problem in both developing and developed countries, and resistance to commonly used antibiotics among enteric pathogens is a major issue. Quinolones have become important agents in the treatment of diarrhoeal diseases because of their excellent in vitroactivity against pathogens and their pharmacological features. In many clinical studies, they appeared to be effective in the treatment of shigellosis and the prevention and treatment of diarrhoea in travellers. Several studies have demonstrated that single-dose therapy with these agents is sufficient in many cases. Their role in the treatment of acute salmonellosis is still controversial, because of their lack of efficacy in eliminating salmonella from the faeces.

Abstract: Fifty episodes of bacteremia caused by coagulase-negative staphylococci at Hacettepe University Hospital over a five-year period were reviewed to evaluate the factors influencing the prognosis. Overall mortality and mortality due to bacteremia were 36% and 24%, respectively. Septic shock was determined to be the only factor adversely influencing mortality in both univariate and multivariate analyses. Age, sex, duration of hospitalization, origin of infection, underlying disease, presence of central intravascular or urinary catheters, and prior antibiotic therapy were not statistically significant parameters in predicting septic shock.

Acute bacterial diarrhoea is still an important disease, especially in developing countries. Resistance to antibiotics among enteric pathogens is relatively common in many parts of the world. The quinolones are active in vitroagainst these organisms, and achieve high stool concentrations. Because of these features, quinolones have been used in the treatment of acute diarrhoeal diseases caused by various bacteria. They appear to be effective in the therapy of shigellosis and travellers’ diarrhoea, as well as in the prevention of diarrhoeal disease in travellers. However, their role in the treatment of salmonella gastroenteritis has not been established yet.

Prosthetic valve endocarditis caused by Pseudomonas aeruginosa is refractory to medical treatment alone and early valve replacement is necessary. We describe a 40-year-old patient in whom endocarditis developed in the early postoperative period, and reoperation was not considered feasible. Ciprofloxacin was administered orally in order to suppress bacteremia for 36 months. Long-term oral ciprofloxacin may provide an opportunity in the treatment of prosthetic valve endocarditis caused by Ps. aeruginosa in patients who are unfavorable candidates for reoperation.

Pseudomonas aeruginosa ABD, which was isolated in October 1991 from blood cultures of a burn patient in Turkey, was resistant to cephalosporins, particularly ceftazidime (MIC, 512 micrograms/ml), penicillins, aztreonam, and meropenem, but not to imipenem. Cephalosporin and penicillin resistance transferred to P. aeruginosa PU21 and was associated with a beta-lactamase with a pI of 6.4 encoded by a 100-MDa plasmid designated pMLH52. Like extended-spectrum TEM and SHV beta-lactamases, this enzyme hydrolyzed penicillins and newer cephalosporins but did not hydrolyze cefoxitin or carbapenems. However, it differed from TEM and SHV derivatives in being a potent oxacillinase, and its encoding gene did not hybridize with probes to TEM and SHV genes. To characterize the enzyme, libraries of total DNA were cloned into plasmid pUC19 and were transformed into Escherichia coli DH5 alpha. Recombinant plasmids that gave ceftazidime resistance all contained a 3.65-kb BamHI fragment. Deletions from this fragment allowed the beta-lactamase gene to be located on a 1.4-kb section of DNA, which contained an open reading frame of 798 bases. This encoded a protein that was deduced to differ from PSE-2 beta-lactamase only in having serine instead of asparagine at position 143 and aspartate instead of glycine at position 157. It is concluded that the resistance of isolate ABD dependent on an extended-spectrum variant of the PSE-2 enzyme. The ability of this enzyme to cause ceftazidime resistance dependent primarily on a low Km for the compound; Vmax remained low. It is proposed that PSE-2 should be transferred to the OXA group as OXA-10 and that the new enzyme be designated OXA-11.

Quinolones have been reported to be active against Brucella species in vitro. In this prospective randomized study, the efficacy and safety of the combination of ofloxacin plus rifampin were compared with the efficacy and safety of doxycycline plus rifampin, both combinations administered for a 6-week period in treatment of brucellosis. Sixty-one patients were enrolled in the study, and 49 had blood or bone marrow cultures positive for Brucella melitensis. Thirty patients received 200 mg of doxycycline plus 600 mg of rifampin once daily, and 31 patients were treated with 400 mg of ofloxacin plus 600 mg of rifampin once daily for 6 weeks. Nine patients in each group had complications of the disease. There was one therapeutic failure in the ofloxacin-rifampin treatment group, and one patient from each group relapsed (3.3% of those in the doxycycline-rifampin treatment group versus 3.2% of those in the ofloxacin-rifampin treatment group). Gastric discomfort was the major side effect observed in 13 patients (43.3%) who received doxycycline plus rifampin, whereas only 2 patients (6.5%) treated with ofloxacin plus rifampin complained of gastric irritation. These results suggest that the combination of ofloxacin plus rifampin administered for 6 weeks is as effective as doxycycline plus rifampin given for the same period, regardless of the presence of complications of the disease.

ABSTRACTBrucellae survive acidic pHs in phagolysosomes. Azithromycin, streptomycin, and quinolones were active against Brucella melitensisat pH 7.0 but not at pH 5.0; rifampin and doxycycline retained activity at pH 5.0. Regardless of pH, azithromycin-rifampin and ofloxacin-rifampin showed less synergy than established streptomycin-doxycycline and rifampin-doxycycline combinations.

Abstract: Cardiac hydatid cyst is an uncommon lesion. The infection, often acquired by children during play with infected dogs, is most common in sheep-raising areas of the world. We report our clinical and surgical experience in the treatment of one of the youngest reported cardiac hydatidosis patients with multivisceral involvement.

Cardiac hydatid cyst is an uncommon lesion, mostly caused by Echinococcus granulosus. Occurrence of the disease in man appears to be limited geographically to areas where close and continuous contact exists between domesticated carnivores such as dogs and ungulates such as cattle and sheep. Generally cardiac hydatid cysts are univesicular. Here we report our clinical and surgical experience of treatment in a case of a multivesicular cardiac hydatid cyst with hepatic involvement.

Bacterial endocarditis caused by Actinobacillus actinomycetemcomitans is a rare disease. A 48-year-old man who had a Starr-Edwards aortic valve prosthesis inserted in 1972 was admitted for evaluation of confusion, headaches, anorexia, weight loss, diarrhea and weakness. Six blood cultures yielded gram-negative organisms which were subsequently identified as A. actinomycetemcomitans. Treatment with ampicillin and gentamicin resulted in cure which has been maintained after an observation period of eleven months. This represents the second report of A. actinomycetemcomitans endocarditis in a patient with a prosthetic valve. Bakterielle Endokarditis durch Befall mit Actinobacillus actinomycetemcomitans ist eine seltene Erkrankung. Ein 48jähriger Mann, dem 1972 eine künstliche Aortenklappe vom Typ Starr-Edwards eingesetzt worden war, wurde zur klinischen Beurteilung eines aus Verwirrung, Kopfschmerzen, Anorexie, Gewichtsverlust, Diarrhoe und Schwäche bestehenden Syndroms stationär aufgenommen. Sechs Blutkulturen wiesen gramnegative Organismen aus, die nachfolgend als A. actinomycetemcomitans identifiziert wurden. Eine Behandlung mit Ampicillin und Gentamycin führte zur Heilung, die nach einer Beobachtungsdauer von elf Monaten anhielt. Dies ist der zweite Bericht über Endokarditis infolge A. actinomycetemcomitans bei einem Patienten mit Klappenersatz.

In this prospective study of enteric fever, 22 patients received 400 mg of pefloxacin twice daily for 5 days (group A) and 24 received 400 mg of pefloxacin twice daily for 7 days (group B). Causative microorganisms were Salmonella typhi (8 in group A, 11 in group B) and Salmonella paratyphi B (14 in group A, 13 in group B). The clinical cure and bacterial eradication rates were 96% (21 of 22) in group A and 100% in group B. In conclusion, 5-day oral administration of pefloxacin was as effective as 7-day treatment of enteric fever caused by Salmonella spp.

Postoperative infections account for a large proportion of hospital-acquired infections, are associated with a high morbidity and mortality, and place a large burden upon the inpatient healthcare budget. Prophylaxis is desirable and is based on a combination of preoperative preparation, surgical techniques, perioperative antibiotic prophylaxis and postoperative wound care. There is considerable evidence that antibiotics are used excessively and inappropriately in the prevention and treatment of hospital-acquired infections, including surgical-site infections. In the case of the latter, timing of prophylaxis is crucial to success yet antibiotics are often administered at the wrong time or for too long a period, with implications for the cost of patient care. Several studies have shown that the local implementation of practice guidelines can yield significant improvements in antibiotic use and the cost of surgical prophylaxis. More rational use of antibiotics is likely to benefit the treatment of future surgical patients by reducing the pressure to select for antibiotic-resistant bacterial pathogens.

Cirrhotic patients with ascites are highly susceptible to spontaneous bacterial peritonitis. Patients with ascites due to causes other than cirrhosis very seldom develop peritonitis. The antibacterial activity of these ascitic fluids is not known. The present study was undertaken to evaluate the bactericidal and opsonic activity in ascitic fluid from patients with and without cirrhosis and in normal (nonascitic) peritoneal fluid. Normal peritoneal fluids of 20 control subjects and ascitic fluids of 22 patients with noncirrhotic ascites all had normal bactericidal activity. The bactericidal activity of ascitic fluid was diminished in all 25 patients with cirrhosis (P <0.00005 by Fisher's exact test). Similar results were found when opsonic activity was evaluated. Complement and immunoglobulin concentrations in cirrhotic ascites were significantly lower than those in the other two groups. The present study demonstrates that noncirrhotic ascitic fluid has antibacterial activity similar to normal peritoneal fluid, whereas cirrhotic ascitic fluid has a marked reduction of both bactericidal and opsonic activities. These defects may explain the high incidence of peritonitis in cirrhotic patients.

Fluconazole has proved to be effective in treating oropharyngeal and esophageal candidiasis in immunocompromised patients. However, sufficient data are lacking regarding the efficacy of this agent in neutropenic hosts. The aim of the present study was to determine the clinical and mycological efficacy of fluconazole and to define the factor(s) affecting the outcome of fluconazole therapy in severely neutropenic patients (peripheral neutrophil count, <500/μL) with cancer who have oropharyngeal and/or esophageal candidiasis. One hundred eleven patients with 129 episodes of candidal infections were treated with intravenous and consequently oral fluconazole (200 mg/d and 100 mg/d, respectively). Overall clinical cure and mycological eradication rates were 82% and 56%, respectively. Persistent neutropenia (P < .01), infection with a non-albicans strain of Candida (P = .012), and administration of antifungal therapy during the second or a later neutropenic episode (P < .002) were independently associated with a worse outcome. We conclude that fluconazole is effective in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer. Effective treatment of the underlying malignancy, with the resultant recovery from neutropenia, and the determination of the species of infecting Candida isolates are required for the prediction of the outcome of antifungal therapy.

The increased susceptibility to infection suggests that patients with cirrhosis have abnormalities in host defense mechanisms. In the present study, serum bactericidal and opsonic activity were evaluated in patients with non-alcoholic cirrhosis. Seven (28 per cent) of 25 patients had diminished bactericidal activity and 14 (61 per cent) of 23 were found to have reduced opsonic activity. Serum C3, C4, and CH50 concentrations were significantly low in patients with diminished bactericidal activity. There was a strong correlation between complement levels and bactericidal activity. Deficient bactericidal and opsonic activities may explain the increased susceptibility to infections in patients with cirrhosis.

A total of 448 episodes of bacteremia due to gram-negative organisms observed during the 7-year period between 1983 and 1989 at Hacettepe University Hospitals were studied for evaluating the factors influencing the prognosis. The overall mortality rate was 45.0%. The mortality rates were not significantly different in “rapidly fatal” and “ultimately fatal” disease groups (48.3% and 45.5%, respectively), whereas it was significantly less (34.8%) in the “nonfatal” disease group compared with the “rapidly fatal” category. There were great differences in the mortality rates among different diseases within the same disease category. Shock, multi-organ failure, source of infection, hospital service, appropriateness of antibiotic therapy, and place of acquisition of infection were found to affect prognosis significantly in multivariate analysis. In conclusion, the identification of prognostic factors is a further step for making necessary interventions in reducing the mortality rate associated with bacteremia due to gram-negative organisms. Underlying disease is still an important prognostic factor; however, a new approach is needed for classification of underlying diseases.