Clinical value of cystatin c determination in children with lymphoma.

Cystatin, a proteinase inhibitor, is involved in the intracellular catabolism of proteins. We investigated the change in concentration of serum Cystatin C (CysC) in children with lymphomas and its diagnostic utility. Twenty-eight newly diagnosed patients with lymphoma were included in this study. The male/female ratio was 20/8, with a median age of 8.5 years (range 3-17 years). Thirteen patients had Hodgkin's lymphoma (HL) and 15 had non-Hodgkin's lymphoma (NHL). Cystatin C concentration was determined at the time of diagnosis and during remission. In the entire group, CysC concentrations at diagnosis and during remission were 0.87+/-0.29 mg/L and 0.86+/-0.21 mg/L, respectively (p=0.93). In the NHL group, CysC concentrations at diagnosis and remission were 0.89+/-0.32 mg/L and 0.85+/-0.23 mg/L, respectively (p=0.73). The CysC concentrations in the HL group at diagnosis and remission were 0.88+/-0.36 mg/L and 0.88+/-0.18 mg/L, respectively (p=0.73). No significant difference was observed between CysC concentrations in the HL (0.88+/-0.36 mg/L) and NHL (0.89+/-0.32 mg/L) groups. Cystatin C concentrations in all the patients with localized versus those with advanced disease were 0.91+/-0.41 mg/L and 0.88+/-0.3 mg/L, respectively (p=0.83). Cystatin C concentrations of the patients with localized and advanced HL were 0.95+/-0.45 mg/L and 0.77+/-0.14 mg/L, respectively, (p=0.41). Cystatin C level was higher in patients with localized disease, in those without B symptoms, and, at diagnosis, in those with an unfavorable response (Tab. 2, Ref. 20). Full Text in free PDF www.bmj.sk.

Simultaneous triple organ specific autoantibody profiling in adult patients with type 1 diabetes mellitus and their first-degree relatives.

AIMS: We aimed to document prevalence and clinical presentations of seropositivities for glutamate decarboxylase (GAD)-antibody, celiac's disease (CD) and autoimmune thyroiditis (AIT) in adult patients with type 1 diabetes mellitus (T1DM), and their first-degree relatives. METHODS: Sixty-five patients with T1DM, 124 first-degree relatives and 65 healthy controls were screened for GAD-antibody, anti-thyroid peroxidase (ATPO), anti-thyroid stimulating hormone receptor (TSHR), anti-tissue transglutaminase and anti-gliadin antibodies in a matched case-control study. RESULTS: Prevalence of more than one seropositivity for CD-associated antibodies in T1DM-group is 6.0 times increased, compared with controls (p < 0.05). ATPO seropositivity is 5.3 times increased in T1DM group (p < 0.05), but TSHR antibody is comparable with controls (p > 0.05). Seropositivities for T1DM, AIT and CD are 4.3, 1.9 and 2.4 times more prevalent among first-degree relatives respectively, compared with controls (p < 0.05). Pathologically confirmed cases with CD among first-degree relatives were all identified at screening. In contrast, all of pathologically confirmed cases with CD in T1DM group, were either previously diagnosed or symptomatic at time of screening. In the group of patients with T1DM, 31% of seropositive cases for anti-ATPO were clinically latent for AIT, and 74% of ATPO (+) cases were identified at current screening study. Sixty-four per cent of ATPO (+) first-degree relatives were clinically latent for AIT, and 54% were identified at screening. CONCLUSION: Type 1 diabetes mellitus, CD and AIT represent a significant overlap in an adult population with already-diagnosed T1DM and their first-degree relatives. With regard to clinical presentations, CD was less likely to be clinically silent than AIT among patients with T1DM.

Use of plasma Epstein-Barr virus DNA monitoring as a tumor marker in follow-up of patients with nasopharyngeal carcinoma: preliminary results and report of two cases.

Recent studies suggest that plasma Epstein-Barr virus (EBV) DNA may reflect tumor burden in patients with nasopharyngeal cancer. A prospective study was initiated to investigate this correlation in 125 patients (34 pretreatment [Group A], 78 in remission [Group B] and 13 relapsed [Group C]) and 19 healthy controls. In group A, EBV DNA was detected in plasma samples of 24 (70%) patients. In Group B, EBV DNA was detected in 7 patients (range 77-13,731 copies/mL) and further imaging in all but one of these patients revealed active disease confirmed by ultrasound-guided fine-needle biopsy. There was only one false-positive case; this patient is currently under follow-up. Here we describe 2 of the 7 patients with detectable plasma EBV DNA in whom recurrence was documented by PET scan during follow-up. Our results showed that in group B the positive predictive value of quantitative analysis of plasma EBV DNA was 85%. Quantitative analysis of EBV DNA in plasma seems to become an integral part of screening, staging, monitoring, and prediction of relapse in patients with nasopharyngeal carcinoma. However, previous studies cannot be considered definitive and more reports on the use of this technique are urgently needed from both endemic and non-endemic regions.

Varicella vaccination in children with lymphoma and solid tumours.

BACKGROUND: Varicella infection can be a severe disease, especially in immunosuppressed patients. Here, experience with live varicella vaccine to prevent varicella infection is reported in children who were undergoing treatment for lymphoma and solid tumours. METHODS: 40 children, aged between 12 months and 15 years with no clinical history of varicella, were vaccinated with live varicella vaccine. All received two doses of the vaccine subcutaneously 4 weeks apart. Serum samples were taken before the first dose and 6 weeks after the second dose of vaccine. RESULTS: Before vaccination, 32 patients were seronegative for varicella and eight were seropositive. Seroconversion was observed 6 weeks after the second dose in 24 of the 32 (75%) seronegative children. In 4 of 8 previously seropositive patients, antibody titres increased after immunisation. Zoster infection occurred 5 weeks after the second dose of vaccine in only one previously seronegative child. 7 children, who had responded to the vaccine, have been exposed to varicella in their families or in school without contracting clinical disease. CONCLUSION: Although the small number of patients in our group prevents us from drawing definitive conclusions, the varicella vaccine seems to be well tolerated and can be administered to children with lymphoma and solid tumours undergoing treatment.

Stenotrophomonas maltophilia: antimicrobial resistance and molecular typing of an emerging pathogen in a Turkish university hospital.

Despite its limited pathogenicity, Stenotrophomonas maltophilia is an emerging nosocomial pathogen. This study investigated the isolation frequency, antimicrobial resistance and genotypic relationships of 205 S. maltophilia isolates from 188 patients in a university hospital between 1998 and 2003. Susceptibility profiles for 11 antimicrobial agents were determined by the NCCLS agar dilution method for non-fermentative bacteria, while enterobacterial repetitive intergenic consensus sequence (ERIC)-PCR and pulsed-field gel electrophoresis (PFGE) were used for genotyping of the isolates. Of the 205 isolates, 56.1% were isolated in the last 2 years of the study. The risk of S. maltophilia isolation was higher in intensive care units, S. maltophilia was isolated mostly (86.8%) after hospitalisation for >or= 48 h, and 90.4% of the patients had underlying diseases. Resistance levels were>60% for all antimicrobial agents tested except co-trimoxazole. High genetic diversity was found among the S. maltophilia isolates, and cross-infection with S. maltophilia was not common. Although ERIC-PCR revealed fewer genotypes than PFGE, it proved to be a rapid and easy method for S. maltophilia genotyping, and was more economical than PFGE.

Antimicrobial resistance of Salmonella enterica group C strains isolated from humans in Turkey, 2000-2002.

Fifty-three Salmonella enterica group C isolates obtained from various human samples (47 stool, 4 blood and 2 urine) in ten provinces of Turkey between 1 July 2000 and 30 June 2002 were serotyped and resistance to antimicrobials was investigated by agar dilution tests. The isolates were identified as S. Choleraesuis (11), S. Hadar (7), S. Irumu (4), S. Virchow (3), S. Tallahassee (3), S. Paratyphi C (2), S. Braenderup (2), S. Othmarschen (2), S. Menston (2), S. Concord (2), S. Infantis (2), S. Kottbus (2), S. Edinburg (1), S. Oranienburg (1), S. Muenchen (1) and S. Malmoe (1). Antimicrobial resistance rates of S. enterica groups C1 and C2 were high for ampicillin (26% and 60%, respectively), amoxicillin/clavulanic acid (11% and 40%), chloramphenicol (16% and 27%) and tetracycline (3% and 40%). The percentages of strains sensitive to all antimicrobials were 58% and 33%, respectively. Multiresistance was not observed in group C1 isolates, but the rate of multiresistant isolates was 13% in group C2. The rate of decreased ciprofloxacin susceptibility (CipL) was 61% in serogroup C1 and 20% in serogroup C2. These results indicated that S. enterica group C infections in humans were not infrequent in Turkey and that multiple antimicrobial resistance was common within these strains.

Epinephrine and endotoxin tolerance differentially modulate serum cytokine levels to high-dose lipopolysaccharide challenge in a murine model.

BACKGROUND: The epinephrine tolerance state has been demonstrated to increase survival in endotoxic shock and was claimed to have cross-tolerance with endotoxin tolerance. With use of these data, we aimed to determine the effect of epinephrine and endotoxin tolerance on major cytokine levels in a lipopolysaccharide challenge in mice. METHODS: Epinephrine tolerance was induced by beginning with a low dose and gradually increasing to a lethal dose. Endotoxin tolerance was induced by injecting saline solution for 4 days and lipopolysaccharide 1 mg/kg on the fifth day. After these procedures, saline solution or 20 mg/kg lipopolysaccharide was injected into animals. Peak serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta, interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 12 (IL-12) were assayed. RESULTS: The lipopolysaccharide injection increased the levels of all the cytokines in the control and epinephrine-tolerant animals. TNF-alpha, IL-6, and IL-10 levels were lower in endotoxin-tolerant animals compared with controls. Epinephrine-tolerant animals had higher levels of TNF-alpha, IL-6, and IL-12 than the controls did. CONCLUSION: Epinephrine tolerance primes for an exaggerated release of TNF-alpha, IL-6, and IL-12 in response to lipopolysaccharide challenge, suggesting anti-inflammatory and immunosuppressive effects by epinephrine. The anti-inflammatory effect was not mediated through increased IL-10 release. Endotoxin tolerance selectively modulated cytokine release.

Reversible expression of flagella in Campylobacter spp.

The in vitro phase variation of flagella and the transition rates between flagellate and aflagellate phenotypes in Campylobacter species including C. jejuni, C. coli, C. lari (thermophilic campylobacters), C. fetus subsp. fetus, C. fetus subsp. venerealis and C. hyointestinalis were investigated. The change from the flagellate to aflagellate phenotype was detected in all of the 12 Campylobacter strains studied. When measured in a motility medium, flagellate to aflagellate transition in thermophilic campylobacters, C. fetus and C. hyointestinalis strains occurred at a rate of 1.8 x 10(-3) to 7.5 x 10(-3), 3.0 x 10(-4) to 7.8 x 10(-4) and 1.8 x 10(-5) to 7.7 x 10(-6) per cell per generation, respectively. Transition from aflagellate to flagellate phenotype occurred at a rate of 5.8 x 10(-6) to 9.3 x 10(-6) per cell per generation in thermophilic campylobacters and 1.0 x 10(-6) to 1.5 x 10(-6) in C. fetus strains. No reversion from aflagellate to flagellate phenotype could be detected in C. hyointestinalis strains. It was concluded that the ability to reversibly express flagella was inherent in the wild-type strains and the transition rates for both directions were consistent for each strain.

In vitro activities of new quinolones against Brucella melitensis isolated in a tertiary-care hospital in Turkey.

We have evaluated the in vitro activities of seven fluoroquinolones against 69 strains of Brucella melitensis. According to their minimum inhibitory concentration for 90% growth (MIC(90)) values, the most active agent was found to be sparfloxacin (MIC(90) 0.12 mg/L) followed by levofloxacin, ciprofloxacin, ofloxacin (MIC(90) 0.50 mg/L) and grepafloxacin (MIC(90) 1 mg/L), gemifloxacin (MIC(90) 2 mg/L) and gatifloxacin (MIC(90) 4 mg/L).

The effect of Helicobacter pylori on neutrophil chemotaxis is independent of cagA.

Sixteen Helicobacter pylori strains were studied in order to determine their neutrophil chemotactic activity and the association with the presence cagA gene. Neutrophil chemotactic activity was detected by a modified Boyden chamber method and the results were expressed in terms of chemotactic index (CI). The presence of cagA was determined by PCR. Of the 16 strains, eight were cagA+ and eight were cagA-. All of the isolated strains showed chemotactic activity. The mean value of CI of the patient group was significantly higher than the negative control (P < 0.01). The mean value of CI of zymosan-activated serum (P < 0.05) and the reference strain H. pylori NCTC 11637 (HP11637) (P < 0.01) was significantly higher than the patient group's mean value of CI. There were no statistical significance in the CI between cagA+ and cagA- strains (P > 0.05). It is concluded that H. pylori attracts neutrophils by chemotaxis, however, there is no association with cagA.

Seroprevalence of Helicobacter pylori infection in an Asymptomatic Turkish population.

OBJECTIVES: Helicobacter pylori infection is recognized as being strongly associated with chronic gastritis, duodenal ulceration and probably gastric carcinoma. Seroepidemiological studies have shown that a large proportion of healthy people have antibodies against H. pylori. A serological study was conducted in an asymptomatic Turkish population to investigate the seropositivity rate of H. pylori and to detect the relationship with age. SUBJECTS AND METHODS: A total of 657 serum samples collected from 331 male and 326 female people in different age groups who had no gastrointestinal complaints were studied by a commercial ELISA test for the presence of H. pylori-IgG antibodies. RESULTS: Three hundred and forty-eight subjects (53%) were seropositive. The overall seropositivity rates did not differ with sex. Antibody prevalence increased progressively with age. The seropositivity rates were as follows: 17.4% < 1 year old; 15.5% aged 1-4; 30.6% aged 5-9; 47.3% aged 10-14; 58.4% aged 15-19; 62.6% aged 20-29; 67.6% aged 30-39; 81.3% aged 40-49; and 66.3% over 50 years of age. CONCLUSIONS: This study indicated that more than 30% of the subjects acquired infection before teenage and that about 70% of adults had antibodies against H. pylori in our population. The high prevalence and early acquisition of H. pylori infection may be related in part to socioeconomic status and traditional living conditions in Turkey.

The effect of tonsillectomy and adenoidectomy on neutrophil chemotaxis.

Although tonsillectomy and adenoidectomy are common surgical procedures, the effects of these operations on the immune system have not been thoroughly determined. Our data on neutrophil chemotaxic functions in a group of 17 patients with chronic tonsillitis and adenoid hypertrophy show that chronic tonsillitis and adenoid hypertrophy impair neutrophil chemotaxic functions and that there is a subsequent normalization of these values following tonsillectomy and adenoidectomy.

Effects of tenoxicam on neutrophil chemotaxis in rheumatoid arthritis and healthy controls.

Using a modified Boyden chambers method, polymorphonuclear leucocyte (pmnl) random migration and chemotactic responsiveness were compared in 20 rheumatoid arthritis patients with that of 10 healthy controls receiving tenoxicam. Random migration and chemotaxis of neutrophils were examined before drug administration, following 2 hours and 7 days of drug administration and one week after the end of the 7-day-administration of this compound. There was no statistically significant difference between the chemotactic migration of neutrophils in healthy volunteers and patients with RA. The mean chemotactic value in patients with RA and healthy controls was significantly low at 2 hours after drug administration when compared with that before drug administration (p < 0.01). The comparison of the decreases in mean chemotactic values in patients with RA and healthy controls showed no statistical difference. At the end of 7-day-administration, neutrophil chemotaxis was significantly decreased in patients with RA (p < 0.01); however, in healthy controls it was decreased as well, but statistical difference could not be obtained. One week after drug withdrawal, neutrophil chemotaxis turned to baseline values in both groups. We suggest that tenoxicam is a potent inhibitor of neutrophil chemotaxis.

Streptococcus pneumoniae penicillin resistance in Turkey.

Resistance of Streptococcus pneumoniae (750) to penicillin, erythromycin, chloramphenicol and trimethoprim/sulfamethoxazole isolated in 4 Turkish hospitals between 1996 and 1999 was evaluated according to year of isolation, patients' age groups and specimen. Penicillin susceptibility was determined by E-test strips and the other antibiotics were tested by disk diffusion test following the NCCLS guidelines in each center. Overall high and intermediate resistance to penicillin was 3% and 29%, respectively. There was a significant difference (p<0.001) between the centers with regard to penicillin resistance. However, there was no significant increase in resistance by year. Penicillin resistance varied significantly among children and adults (36% versus 25%) and according to the specimen. Highest rate of penicillin resistance was observed in respiratory specimens (36%) followed by ear exudates (33.5%). In blood isolates, resistance to penicillin was 28.6%. Overall resistance to erythromycin was 8%, to chloramphenicol 5% and to trimethoprim-sulfamethoxazole 47%. Although overall penicillin resistance in these Turkish S. pneumoniae isolates is high, resistance rates vary in each center and have not increased from 1996 to 1999.

Non tuberculous mycobacteria (NTM) in patients with underlying diseases: results obtained by using polymerase chain reaction-restriction enzyme analysis between 1997-2002.

In this study, we aimed to evaluate the frequency of non-tuberculous mycobacteria (NTM) isolated from clinical specimens using Polymerase Chain Reaction-Restriction Enzyme Analysis (PCR-REA) and to investigate the patients who had clinically significant NTM infections in our hospital through the five year period from May 1997 to June 2002. A total of 364 mycobacterial strains isolated from clinical specimens which gave positive growth index in the BACTEC 460 radiometric system in Hacettepe University Hospital Clinical Microbiology Laboratory were evaluated by PCR-REA and clinical data were obtained from the patient records. Three hundred and one of the strains (82.7%) were identified as Mycobacterium tuberculosis and 63 (17.3%) were identified as nontuberculous mycobacteria. Seven (11.1%) of 63 NTM patients were regarded as having clinical mycobacteriosis. Chronic obstructive pulmonary disease and other pre-existing lung diseases were seen in 39 (61.9%) of the patients, 11 (17.5%) of'the patients had chronic renal failure. Four (6.3%) and 9 (14.3%) of them had AIDS and carcinomas, respectively. PCR-REA was found to be a reliable method for typing of our mycobacterial isolates to the species level. These data may shed light on the epidemiology of the mycobacterial species and help to select a proper treatment regimen.

Effect of some anti-inflammatory drugs on human neutrophil chemotaxis.

The effects of piroxicam, tenoxicam, diclofenac sodium, acetylsalicylic acid and tiaprofenic acid on the chemotaxis and random migration of human polymorphonuclear leukocytes were investigated, using zymosan-activated serum as chemo-attractant, with a modified Boyden chamber technique. All five compounds significantly reduced chemotaxis. The random migration of polymorphonuclear leukocytes was inhibited by piroxicam, diclofenac sodium and tiaprofenic acid but not by tenoxicam or acetylsalicylic acid. The inhibitory effect of these non-steroidal anti-inflammatory drugs on polymorphonuclear leukocyte chemotaxis and on random migration was generally dose-dependent. The results suggest that the drugs studied may have a direct effect on polymorphonuclear leukocyte chemotaxis and that this activity may contribute to their anti-inflammatory properties.

Helicobacter felis as a cofactor alone or together with stress in cryptosporidial activation in mice.

Cryptosporidiosis is caused by a protozoan parasite, mainly found in animals, which usually results in transient, mild gastroenteritis in humans but can cause severe and prolonged disease in immunocompromised individuals. Immunocompetent mice, naturally infected with Cryptosporidium muris, were used to investigate the effects of inoculation with Helicobacter felis and of stress on the activity of the C. muris infection, as indicated by histopathological examination of their stomachs. The results indicate that both H. felis inoculation and/or stress activate C. muris and cause gastric inflammation. The extent of the activation of C. muris depends on the duration of the stress.

Helicobacter pylori infection in symptomatic and asymptomatic children: a prospective clinical study.

It is well known that Helicobacter pylori infection is extremely common throughout the world, but most infected persons do not develop ulceration and remain asymptomatic. This study was undertaken in order to determine the prevalence of H. pylori infection, the age distribution, and the factors that may affect the frequency of H. pylori infection. We evaluated the presence of antibody against H. pylori in children and adolescents, we also assessed the efficacy of non-invasive and invasive methods for detection of H. pylori infection in children who had undergone upper gastrointestinal endoscopy. We evaluated 43 males and 18 females whose ages ranged from 1 to 17 years (mean age: 9.4 +/- 4.2). 29 of all cases were symptomatic and 32 were asymptomatic. H. pylori infection was present in 49% of the studied cases. The data were analysed by Fisher's exact chi-square and Mantel-Haenszel tests. It was found that H. pylori infection graphically increased with age in both groups from 25% at ages 3-5 to 80% at ages 16-20. But no association was determined statistically between age and H. pylori positivity (p < 0.05). H. pylori infection was determined in 14 (48%) and 16 (50%) cases in symptomatic and asymptomatic groups respectively. There was no significant difference between H. pylori and either group (p > 0.05). According to the endoscopy findings, the symptomatic group was divided into two subgroups: children with peptic ulcer and children with non-ulcer dyspepsia (NUD). An attempt was made to compare ulcer, non ulcer dyspepsia and asymptomatic cases with H. pylori positivity, but no significant relation could be established between the groups (p > 0.05). 14 (23%) of the cases had previous gastric and/or intestinal complaints in their parents (positive family history). There was a significant, statistically positive relation between family history and symptoms (p < 0.01). Nevertheless, no association was found between H. pylori infection and family history (p > 0.05). There were no significant differences in H. pylori infection related to sex, type of housing, location of housing, socio-economic status (SES) or source of water supply. It is concluded that H. pylori infection has a high prevalence in our country. Although endoscopic evaluation is an invasive method, under our conditions, histopathological examination with 97% is shown to be much more sensitive in determination of H. pylori infection. Since no community difference was determined in the prevalence of H. pylori infection, all children should be considered to be under the threat of the same risk.

Adrenalin tolerance does not prevent bacterial translocation in a murine burn model.

Burn injury causes mesenteric vasoconstriction and bacterial translocation. Since catecholamines are powerful vasoconstrictors and elevated immediately after burn injury, we hypothesised that adrenaline tolerance might decrease burn-induced mesenteric vasoconstriction and bacterial translocation. Adrenaline tolerance was developed in Swiss albino mice. Adrenaline tolerant and control animals were subdivided into sham-burn and burn subgroups. 24 h after sham-burn or burn injury, specimens were obtained for microbiological evaluation. Also, in a separate group of adrenaline tolerant and control animals, superior mesenteric blood flow was measured. Burn injury increased bacterial translocation rate in both control (P = 0.001) and adrenaline tolerant groups (P = 0.0351). The caecal bacterial level increase was significant after burn injury in control groups (P = 0.0004) but was not significant in adrenaline tolerant animals (P = 0.743). Mesenteric blood flow was decreased significantly by burn injury in both control and adrenaline tolerant animals (P < 0.00001). The results showed that catecholamines do not mediate postburn mesenteric vasoconstriction or bacterial translocation.

Evaluation of the microbiology of chronic sinusitis.

Chronic sinusitis is one of the most common diseases treated in outpatient centres. In this prospective study, 49 patients with the diagnosis of chronic maxillary sinusitis were evaluated microbiologically by using sinus swab, irrigation fluid and sinus mucosal tissue specimens obtained during endoscopic sinus surgery. There was no bacterial growth in seven cases. In the remaining 42 cases a total of 89 bacteria were isolated, 28 of them being classical pathogens and 61 being non-classical pathogens. Among the classical pathogens Staphylococcus aureus was the most common one. The correlation between the isolates obtained from maxillary sinus and isolates obtained from throat, nose and nasopharynx did not have a predictive value. Since the overall rate of classical pathogen isolation from patients with chronic sinusitis was not significantly high, the possible role of factors other than bacterial growth should be identified in the pathogenesis of chronic sinusitis.