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Background and ObjectivesAging is characterized by a functional shift of the immune system toward a proinflammatory phenotype. This derangement has been associated with cognitive decline and has been implicated in the pathogenesis of dementia. Diet can modulate systemic inflammation; thus, it may be a valuable tool to counteract the associated risk for cognitive impairment and dementia. The present study aimed to explore the associations between the inflammatory potential of diet, assessed with an easily applicable, population-based, biomarker-validated diet inflammatory index (DII), and the risk for dementia in community-dwelling older adults.MethodsIndividuals from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD) were included in the present cohort study. Participants were recruited through random population sampling and were followed up for a mean of 3.05 (standard deviation 0.85) years. Dementia diagnosis was based on standard clinical criteria. Those with baseline dementia or missing cognitive follow-up data were excluded from the analyses. The inflammatory potential of diet was assessed through a DII score that considers literature-derived associations of 45 food parameters with levels of proinflammatory and anti-inflammatory cytokines in the blood; higher values indicated a more proinflammatory diet. Consumption frequencies were derived from a detailed food frequency questionnaire and were standardized to representative dietary intake normative data from 11 different countries. Analysis of dementia incidence as a function of baseline DII scores was performed by Cox proportional hazards models.ResultsAnalyses included 1,059 individuals (mean age 73.1 years, 40.3% male, mean education 8.2 years), 62 of whom developed incident dementia. Each additional unit of DII score was associated with a 21% increase in the risk for dementia incidence (hazard ratio 1.21 [95% confidence interval 1.03–1.42]; p = 0.023). Compared to participants in the lowest DII score tertile, participants in the highest one (maximal proinflammatory diet potential) were 3 (95% confidence interval 1.2–7.3; p = 0.014) times more likely to develop incident dementia. The test for trend was also significant, indicating a potential dose-response relationship (p = 0.014).DiscussionIn the present study, higher DII scores (indicating greater proinflammatory diet potential) were associated with an increased risk for incident dementia. These findings might avail the development of primary dementia preventive strategies through tailored and precise dietary interventions.

Neurobrucellosis presents in various clinical forms and should always be considered in neurological patients in highly endemic areas such as the Mediterranean basin. Establishing a diagnosis can be challenging since serological testing can sometimes yield negative results. We present a rare case of a seronegative relapse of neurobrucellosis in a patient who had been successfully treated for systemic brucellosis. Oligoclonal bands, an agglutination test, and 16S rRNA sequencing of cerebrospinal fluid proved essential in unmasking a confined central nervous system relapse. This case reinforces the need for establishing diagnostic criteria for neurobrucellosis, which could potentially include oligoclonal bands and an agglutination test on the cerebrospinal fluid.

Introduction/Objectives Periodontitis comprises of a wide range of inflammatory conditions of the gums leading to soft tissue damage and attachment loss. The initiation of periodontitis constitutes a rather complex disease pathogenesis which is based on pathogenic shifts of the oral microbiota combined with the host-microbiome interactions. The severity of the periodontitis is multifactorial depending on genetic, environmental, as well as host immunity factors. Data and sources To make an inclusive analysis on the periodontitis therapeutics, reading of the recent relevant literature was carried out using the MEDLINE/PubMed database, Google Scholar and the NIH public online database for clinical trials (http://www.clinicaltrials.gov). Conclusions Tackling the inflammation associated periodontal defects can be succeeded with conventional therapy or resective and regenerative treatment. To date, the mechanical removal of the supragingival and subgingival biofilm is considered the “gold standard” of periodontal therapy in combination with the use of antibacterial compounds. The antimicrobial resistance phenomenon tends to turn all the currently applied antibacterials into “endangered species”. Ongoing efforts through the conduct of clinical trials should be focused on understanding the advantages of modern approaches in comparison to traditional therapies., Periodontitis; Oral microbiome; Biofilm; Therapeutics; Curcumin; Photodynamic therapy.

Anti-SARS-CoV-2 spike RBD (receptor-binding domain) IgG antibody levels were monitored in 1643 volunteer healthcare workers of Eginition, Evangelismos, and Konstantopoulio General Hospitals (Athens, Greece), who underwent vaccination with two doses of COVID-19 BNT162b2 mRNA vaccine (Pfizer) and had no history of SARS-CoV-2 infection. Venous blood was collected 20–30 days after the second vaccine dose and anti-RBD IgG levels were determined using CMIA SARS-CoV-2 IgG II Quant (Abbott) on ARCHITECT i System or ADVIA Centaur SARS-CoV-2 IgG (Siemens) on Centaur XP platform. From the total population of 1643 vaccinees (533 M/1110 F; median age = 49; interquartile range-IQR = 40–56), 1636 (99.6%) had anti-SARS-CoV-2 IgG titers above the positivity threshold of the assay used. One-Way ANOVA Kruskal-Wallis H test showed a statistically significant difference in the median of antibody titers between the different age groups (p < 0.0001). Consistently, Spearman’s correlation coefficient (r) for IgGs and age as continuous variables was −0.2380 (p = 1.98 × 10−17). Moreover, antibody titers were slightly higher by 1.2-mean fold (p = 3 × 10−6) in the total female population of the three hospitals (median = 1594; IQR = 875–2584) as compared to males (median = 1292; IQR = 671.9–2188). The present study supports that BNT162b2 vaccine is particularly effective in producing high anti-SARS-CoV-2 IgG levels in healthy individuals, and this humoral response is age- and gender-dependent.

Purpose To estimate the roles of triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio and uric acid in predisposition for metabolic syndrome (MetS) and its components in healthy children. Methods Anthropometric and biochemical analyses were performed on 110 children, aged 5 to 12 years, from the Greek county of Laconia. The children were studied as a whole population and in separate groups according to age and predisposition to MetS after taking into consideration International Diabetes Federation criteria, body mass index, and lipid profile. Results Seventeen percent of children exhibited predisposition to MetS, while 39.1% had TG/HDL ratio >1, and 3.64% had high level of uric acid. According to a receiver operating characteristic curve analysis, the relative probability for MetS predisposition sextupled when TG/HDL ratio was ≥1 (odds ratio [OR], 5.986; 95% confidence interval [CI], 1.968–18.205). Children in the total population and those aged < 9 years had a greater probability for increased low-density lipoprotein (LDL) cholesterol (OR, 3.614; 95% CI, 1.561–8.365) when TG/HDL ratio was ≥ 1. The TG/HDL ratio was positively correlated with body mass index (BMI) (P=0.035) in children without MetS, cholesterol in the total population (P=0.06) and children ≥9 years old (P=0.026), and with LDL in the total population and both age groups (P=0.001). The TG/HDL ratio was also positively correlated with alanine aminotransferase in the total population (P=0.033) and gamma-glutamyl transferase in most studied groups (P

Background Apoptosis antigen 1/FAS receptor (APO1/Fas) signaling in endothelial cells plays a significant role in angiogenesis while increased mean platelet volume (MPV) is an important marker for platelet activation. We investigated the possible correlation between APO1/Fas and both metabolic parameters and platelet activity (indicated by the MPV) in a healthy pediatric population. Methods One hundred and eighty-five children, aged 5–17 years old, were enrolled in the study. The participants were divided into subgroups according to their age and body mass index percentile (BMI%). APO1/Fas was measured by enzyme-linked immunosorbent assay (ELISA) and MPV by the MEK-6410K. Results Eighty-one children (43.8%) had excess weight, which was more prevalent in children ≤9 years of age. Sixty-five children (35.1%) exhibited a predisposition for metabolic syndrome. A negative correlation was found between APO1/Fas and predisposing factors for metabolic syndrome: Glucose, cholesterol, uric acid, low-density lipoprotein (LDL), and triglycerides. In contrast, a positive correlation was found between APO1/Fas and C-reactive protein (CRP). Receiver operating characteristic (ROC) analysis showed a predisposition to metabolic syndrome when APO1/Fas was Conclusions APO1/Fas expression is associated with a lower predisposition to metabolic syndrome may be through endothelial homeostasis, the induction of apoptosis of cells involved in atherosclerosis, and platelet activity. It may also enhance CRP-mediated noninflammatory clearance of apoptotic cells. Early monitoring of all the components of metabolic syndrome in overweight children is important in order to prevent metabolic and cardiovascular complications.

Background There are few studies about the presence of murine typhus in Greece. Our objective was to conduct a large scale retrospective investigation to determine the clinical and epidemiological features of patients diagnosed with murine typhus in Greece. Methodology/Principal findings From 2012 to 2019 serum samples from hospitalized patients and outpatients throughout Greece suspected for murine typhus infection were tested by immunofluorescence assay for Rickettsia typhi. Immunofluorescence positive samples obtained since 2016 were also tested by qPCR targeting R. typhi. Clinical and epidemiological data were retrospectively collected for the patients with confirmed murine typhus. Overall, we tested 5,365 different patients and, in total, 174 patients from all geographic regions of Greece were diagnosed with murine typhus. The most frequently reported sign or symptom was fever (89%), followed by headache (84%) and rash (81%). The classical triad of fever, headache, and rash was present in 72% of patients during their illness. Severe infections with complications including acute renal failure or septic shock were not recorded. The majority of cases (81%) occurred during May–October and peaked in June and September. Most of patients (81%) infected in Athens, recalled that their only activity the last weeks before symptoms onset was swimming on the beach and 59% of them also reported an insect bite while sunbathing. Conclusions/Significance Our results may reflect the reemergence of murine typhus in Greece and we highlight the importance of awareness of this difficult-to-recognize undifferentiated febrile illness.

Background Nationwide data on cardiovascular risk factors prevalence is lacking in Greece. This work presents the findings of the national health examination survey EMENO (2013–2016) regarding the prevalence of hypertension, hypercholesterolemia, diabetes, obesity and smoking. Methods A random sample of adults (≥18 years) was drawn by multistage stratified random sampling based on 2011 Census. All EMENO participants with ≥1 measurement of interest [blood pressure (BP), fasting glucose, HbA1c, total cholesterol (TC), Body Mass Index (BMI)] were included. Hypertension was defined as BP ≥ 140/90 mmHg and/or antihypertensive treatment; diabetes as fasting glucose≥126 mg/dL and/or HbA1c ≥ 6.5% or self-reported diabetes; hypercholesterolemia as TC ≥ 190 mg/dL. Sampling weights were applied to adjust for study design and post-stratification weights to match sample age and sex distribution to population one. Non-response was adjusted by inverse probability weighting. Results Of 6006 EMENO participants, 4822 were included (51.5% females, median age:47.9 years). The prevalence of hypertension was 39.2%, higher in men (42.4%) than in women (36.1%); of hypercholesterolemia 60.2%, similar in men (59.5%) and women (60.9%); of diabetes 11.6%, similar men (12.4%) and women (10.9%); of obesity 32.1%, higher in women (33.5% vs 30.2%), although in subjects aged 18–40 year it was higher in men; of current smoking 38.2%, higher in men (44.0%) than in women (32.7%). The prevalence of all risk factors increased substantially with age, except smoking, which followed an inverse U shape. Conclusions The burden of cardiovascular risk factors among Greek adults is alarming. There is considerable preventive potential and actions at health care and societal level are urgently needed.

Cefepime/zidebactam is in clinical development for the treatment of carbapenem-resistant Gram-negative infections. MICs of cefepime/zidebactam (1:1) and comparators against Enterobacterales (n = 563), Pseudomonas (n = 172) and Acinetobacter baumannii (n =181) collected from 15 Greek hospitals (2014-2018) were determined by reference broth microdilution method. The isolates exhibited high carbapenem resistance rates [(Enterobacterales (75%), Pseudomonas (75%) and A. baumannii (98.3%)]. Cefepime/zidebactam showed MIC50/90 of 0.5/2 mg/L, against Enterobacterales including metallo-β-lactamases (MBL)-producers. Reduced susceptibility rates to tigecycline (16.8%), colistin (47.4%), ceftazidime/avibactam (59.8%), and imipenem/relebactam (61%) indicated high prevalence of multi-drug resistance among Greek Enterobacterales. Cefepime/zidebactam exhibited MIC50/90 of 8/16 mg/L against Pseudomonas including MBL-producers. The MIC50/90 of ceftazidime/avibactam and imipenem/relebactam were high (≥32 mg/L). Cefepime/zidebactam showed MIC90 of 64 mg/L against A. baumannii which is within its therapeutic scope. Other antibiotics including colistin showed limited activity against A. baumannii. The activity of cefepime/zidebactam against multi-drug-resistant isolates is attributable to zidebactam mediated novel β-lactam-enhancer mechanism.

Background Listeria monocytogenes is an opportunistic pathogen of the central nervous system commonly associated with impaired cell-mediated immunity. We hereby present a case of adult neurolisteriosis where the only immunological feature persistently present was serum IgM deficiency, suggesting that non-specific humoral immunity may also play a central role in the control of neuroinvasion by Listeria monocytogenes. Case presentation A 62-year-old male who had never experienced severe infections presented with headache, nuchal rigidity and confusion. Neuroimaging was normal and lumbar puncture revealed pleiocytosis (760 leukocytes/mm3) and hypoglycorrhachia (34 mg/dL). The patient was treated empirically for bacterial meningitis. Indeed, further analysis of the CSF showed infection by Listeria monocytogenes, which was accompanied by reduced serum IgM levels that persisted well beyond the period of acute bacterial infection. Levels of IgG and IgA isotypes, along with peripheral blood counts of major leukocyte subsets, were at the same time largely preserved. Intriguingly, the absence of membrane-bound IgM on B cells was essentially complete in the acute post-infection period leading to a remarkable recovery after 12 months, suggesting that mechanisms other than defective membrane expression are underlying serum deficiency. Conclusions As far as we know, this is the first reported case of neurolisteriosis associated with IgM deficiency in an adult individual without a history of severe infections or other underlying conditions. A possible role of circulating IgM against invasive disease caused by Listeria monocytogenes, particularly in the early course of host-pathogen interaction, is discussed.

Purpose To investigate the effect of lifestyle habits in childhood Metabolic Syndrome (MTS). Design and Methods Descriptive correlation study with 480 participants (5–12 years old) using a specially designed questionnaire was conducted. Anthropometric and biochemical analyses were performed. Results Fifteen percent of children exhibited predisposition for MTS. Regarding sleep habits, logistic regression analysis (LRA) showed that hour of sleep -before 22:00- was associated with decreased waist circumference (WC%) (p = .026). Midday siesta was negatively correlated with systolic (SBP) (p = .001) and diastolic blood pressure (DBP) (p = .046). In children without MTS, lack of sleep and night time sleep was positively correlated with DBP (p = .044) and fasting blood glucose (FBG) (p = .005). Regarding nutrition habits, fast food consumption was positively correlated with SBP (p = .006) and meat consumption was positively correlated with both Body Mass Index% (BMI%) (p = .038) and WC% (p = .023). LRA showed that fruit (p = .001) and legume (p = .040) consumption was associated with decreased FBG; fish consumption with decreased Low Density Lipoprotein (LDL) cholesterol (p = .031), vegetable (p = .054) and cereal consumption (p = .012) with decreased DBP. In children with MTS, fruits were associated with increased FBG (p = .034). In children without MTS, meat consumption was associated with increased LDL (p = .024), cereal with increased WC% (p = .002) and olive products with increased High Density Lipoprotein (HDL) cholesterol and BMI% (p = .037). Conclusions The adoption of both balanced diet and sleep habits seemed to be crucial for the prevention of MTS. Practice Implications Clinical health nurses could develop and implement preventive intervention programs in order to avoid metabolic complications in adulthood.

The role of clinical pathologists or laboratory-based physicians is being challenged on several fronts—exponential advances in technology, increasing patient autonomy exercised in the right to directly request tests and the use of non-medical specialists as substitutes. In response, clinical pathologists have focused their energies on the pre-analytical and postanalytical phases of Laboratory Medicine thus emphasising their essential role in individualised medical interpretation of complex laboratory results. Across the European Union, the role of medical doctors is enshrined in the Medical Act. This paper highlights the relevance of this act to patient welfare and the need to strengthen training programmes to prevent an erosion in the quality of Laboratory Medicine provided to patients and their physicians.

Background To investigate the association between frailty, Parkinson’s disease (PD), and the probability of prodromal Parkinson’s disease (prodromal PD) in Greek community-dwelling older individuals. Methods Parkinson’s disease diagnosis was reached through standard clinical research procedures. Probability of prodromal PD was calculated according to the International Parkinson and Movement Disorder Society’s research criteria for PD-free participants. Frailty was evaluated according to definitions of the phenotypic and multidomain approach. Logistic and linear regression models were performed to investigate associations between frailty (predictor) and the probability of prodromal PD, either continuous or dichotomous (≥30% probability score), or PD (outcome). Results Data from 1765 participants aged 65 and older were included in the present analysis. Parkinson’s disease and prodromal PD prevalence were 1.9% and 3.0%, respectively. Compared to nonfrail participants, those who were frail, as identified with either the Fried frailty phenotype or Frailty Index had approximately 4 (odds ratio [OR] 4.09, 95% confidence interval [CI] 1.54–10.89) and 12 times (OR 12.16, 95% CI 5.46–27.09) higher odds of having a PD diagnosis, respectively. Moreover, compared to the nonfrail, frail participants as identified with either the Fried frailty phenotype or Frailty Index had 2.8 (OR 2.83, 95% CI 1.09–7.37) and 8.3 times (OR 8.39, 95% CI 4.56–15.42) higher odds of having possible/probable prodromal PD, respectively. Conclusions Frailty status was associated with prodromal PD and PD, suggesting common characteristics or underlying mechanisms of these conditions. Although prospective studies are warranted, acknowledging the possible association of frailty, PD, and prodromal PD may improve their clinical management.

We report a rare case of non–cystic fibrosis bronchiectasis accompanied by protracted infection with Aggregatibacter aphrophilus in a 12-year-old boy with haemoptysis. Keywords: Aggregatibacter aphrophilus, BAL, bronchoscopy, HACEK, non-CF bronchiectasis

The aim of this study was to compare Bangladeshi immigrants with diabetes to native Greeks with diabetes and to distinguish the different risk factors for polyneuropathy (PN) in the two ethnic groups. Subjects were recruited from the outpatient diabetic clinic of a general hospital. A total of 111 Bangladeshi immigrants (97 men and 14 women of mean age 47 years) and 101 native Greeks (82 men and 19 women of mean age 49 years) were included in the study. Sex, mean age, age at diabetes diagnosis, and diabetes duration did not differ between the two groups. PN was diagnosed in 53 (48%) Bangladeshi and in 59 (58%) Greek patients (p = 0.12). Large fiber neuropathy was less prevalent among Bangladeshis (18%) than in Greeks (53%) (p

Prayer marks (PMs) are commonly occurring dermatologic changes in muslims who pray and develop over a long period of time as a consequence of repeated and extended pressure. PMs need careful examination especially for patients with diabetes, who are more vulnerable due to predisposing factors such as venous insufficiency and peripheral neuropathy. A total of 166 patients with diabetes (150 males, 16 females) and 65 normal subjects from Bangladesh were examined for the appearance of PMs. Twenty-eight patients (16.9 %) and one normal subject (1.5 %) had PMs. The marks were not itchy or painful and they were observed on the dorsal aspect of the left foot, which was attributed to a more typical prayer position that placed pressure on the left foot. PMs are not a rare clinical entity among muslim patients with diabetes and most clinicians should be aware of it as it can be the predominant cause of an ulcer.

Lower prevalence of cerebrospinal fluid oligoclonal IgG bands (IgG-OCBs) has been reported in multiple sclerosis (MS) patients from Southern Europe compared to other western countries.We aimed to determine the prevalence of CSF OCBs in Greek MS patients and to examine their relation with some selected clinical and demographical features.Included patients fulfilled the 2005 McDonald criteria for definite MS (CDMS) or clinically isolated syndrome (CIS) and had a spinal tap performed between 2006 and 2010. Paired CSF and plasma samples were analyzed using isoelectric focusing followed by IgG-specific immunofixation. A pattern of two or more bands present only in the CSF was defined as positive. OCB status was correlated with age at disease onset, initial symptomatology, relapse rate, disease subtype, disease duration, medication, EDSS score and MSSS.Of the 231 included patients (53.2% with CDMS and 48.6% with CIS) 67.5% had OCBs. The prevalence of positive patterns did not differ between CIS and CDMS patients (67.6% vs. 67.5%, respectively). OCB-positive patients were younger than OCB-negative patients (35.2±10.3 vs. 38.7±11.8 years respectively, p=0.022) and had more frequently cervical spinal cord lesions (x2=7.08, p=0.008). No difference was observed between the two subgroups in the other studied disease parameters.Despite the lower frequency of positive IgG-OCB patterns in our patients, both subgroups were mostly similar with regard to their clinical and demographic characteristics suggesting that the OCB status lacks prognostic significance in MS.

Lactobacilli are human commensals found in the gastrointestinal and genitourinary tract. Although generally conceived as non-pathogenic microorganisms, the existence of several reports implicating them in certain severe pathological entities renders this species as opportunistic pathogens. The case of a 58-year-old woman with mixed Lactobacillus infection is described. The patient was admitted in an outpatient clinic with community acquired pneumonia, and on the third day of hospitalization she presented rapid pneumonia deterioration. Subsequent imaging techniques revealed increased pleural empyema in alignment with the general deterioration of her clinical condition. Pleural fluid culture revealed the presence of Lactobacillus delbrueckii and Lactobacillus gasseri and the infection was successfully treated with clindamycin. Five months after hospital discharge and an overall good condition, the patient developed signs of dysphagia and upon re-admission an inoperable esophageal carcinoma was diagnosed. The patient succumbed to the cancer 11 months later. Herein, we report for the first time a mixed respiratory infection due to lactobacilli, possibly associated with a formerly unveiled esophageal malignancy.

The present study aimed to investigate for the first time, the alteration of α-N-acetylgalactosaminidase (nagalase) concentration in alcohol-dependent individuals without liver disease, before, during and at the end of the detoxification therapy.Forty-eight alcohol-dependent individuals without liver disease who were admitted for alcohol detoxification, and eighty-four healthy controls participated in this study. Patients' blood was obtained upon admission, two weeks later and after the completion of the detoxification period (4-5 weeks). Nagalase concentration in serum was assessed by enzyme-linked immunosorbent assay.Nagalase concentration was significantly elevated in the patient samples in all serum collections as compared to the normal controls, with a progressive fall from admission to discharge (p-value0.001). Values differed significantly among the three time points, with a net shift to decrease, but remained still high, above normal control level at the end of the therapy. No significant correlations were detected among the nagalase levels and the liver enzymes values. Moreover, no significant correlation was found between the alterations of nagalase concentrations and the amount of consumed alcohol.The high nagalase concentrations in alcohol abuse might be associated with macrophage impairment through decreasing the endogenous macrophage-activating factor (MAF) production by Gc-protein. The possible pathogenetic association between nagalase activity and alcohol overconsumption remains a matter of further investigation. Nagalase could also serve as a marker of alcohol overconsumption for the evaluation of alcohol-dependent individuals before, as well as during the detoxification therapy.

Background and Objectives: Acute bacterial meningitis is one of the most severe infectious diseases, affecting mainly infants and, secondarily, older children and adolescents. Diagnosis in the early stages is often difficult and despite treatment with appropriate antibiotic therapy, the case fatality rate remains high. In the present study, the incidence of bacterial meningitis was registered in a general pediatric hospital in Athens, Greece, during a 9-year period (2000–2008), and the use of molecular methods in the diagnosis of bacterial meningitis versus the conventional cultural methods was evaluated. The impact of vaccination against meningitis-causing bacteria on the incidence of bacterial meningitis was also assessed. Methods: From a total of 1833 children hospitalized with suspected clinical symptoms and signs of meningitis, all cerebrospinal fluid (CSF) and blood samples were analyzed by white blood cell (WBC) count, measurement of glucose, protein, and C-reactive protein (CRP) levels, as well as by conventional bacteriologic culture methods. If samples showed altered CSF markers that were consistent with meningitis in general, they were further investigated by PCR for bacterial pathogens. Results: Of the 1833 patients, 289 (15.76%) were found to be positive for meningitis after CSF examination, based on white blood cell count and differentiation, glucose, protein, and CRP. Fifty-six of the 289 (19.37%) had confirmed bacterial meningitis, as diagnosed by either culture and/or PCR. Of these 56 cases, 44 (78.6%) were detected only by PCR, and 12 cases (21.4%) were confirmed by PCR and culture. The predominant microorganism was Neisseria meningitidis serogroup B (n = 40; 71.4%), followed by Streptococcus pneumoniae not typed [NT] (n = 7; 12.5%), Streptococcus spp. (n = 4; 7.1%), Haemophilus influenzae NT (n = 2; 3.6%), and S. pneumoniae serotype 3, Streptococcus group B, and S. pneumoniae serotype 18C (each n=1; 1.8%). Conclusion: In Greece, according to data from the National Meningitis Reference Laboratory, vaccination against N. meningitidis serogroup C since 2001 led to a 10-fold decrease in the incidence of meningitis cases, vaccination against S. pneumoniae serotypes included in the heptavalent conjugate vaccine since 2005 led to a 3.4-fold incidence decrease, and vaccination against H. influenzae type b since 1992 led almost to an absence of cases. In the population of the present study, none of the cases were caused by the above-mentioned vaccine pathogens, except for one S. pneumoniae serotype 18C case with no history of past vaccination. The introduction of vaccination against meningitis-causing bacteria has drastically decreased the emergence of the infection. The improved molecular amplification assays proved to be superior to conventional bacteriologic methods and should be introduced into routine diagnosis, as well as the epidemiologic surveillance of bacterial meningitis.

Background The course of Interleukin-7 (IL-7), Interleukin-10 (IL-10) and Granulocyte Colony Stimulating Factor (G-CSF) was investigated in alcohol-dependent individuals without liver disease in order to ascertain the use of these cytokines as markers for the follow-up testing and the outcome of the detoxification treatment. Methods Forty-eight alcohol-dependent individuals were admitted for alcohol detoxification. Blood was obtained upon admission, two weeks later and after the completion of the detoxification period (4–5 weeks). Serum IL-7, IL-10 and G-CSF were measured with a commercially available sandwich enzyme immunoassay. Results IL-7 concentration was steadily high from admission up to two weeks later and then showed a fall, yet still remaining significantly higher than in the control group at the end of the detoxification treatment. IL-10 concentration was significantly low on admission, presenting a linear increase during therapy and remained insignificantly low at the end. G-CSF was significantly elevated on admission and presented a linear fall ending up in almost normal values at the end of the detoxification therapy. Conclusions The alterations in the concentration of IL-7, IL-10 and G-CSF and their trend to normalization during the detoxification therapy are indicative of the generalized immune system disorder, caused by alcohol abuse. Further studies will help in further elucidating the pathophysiology of the immune system function in alcohol abuse, while immunological parameters might serve as biological markers and diagnostic tools for the assessment of the course and the outcome of the detoxification therapy.

SUMMARY: Background: Telomerase preserves telomeres’ function and structure preventing cellular senescence. Its activity is reduced in peripheral blood mononuclear cells (PBMC) of haemodialysis (HD) patients. The purpose of this study is to investigate the potential correlation between increased oxidative stress/inflammation and telomerase activity in PBMC of HD patients. Methods: Telomerase activity was measured by PCR-ELISA in PBMC isolated from a group of 42 HD patients and 39 subjects with estimated glomerular filtration rate ≥80 mL/min (control group). Serum oxidized low-density lipoprotein (ox-LDL), tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were also measured in both groups by ELISA. Results: Ox-LDL was negatively correlated to percentage telomerase activity in PBMC (r = −0.506, P = 0.000 in the whole group of 81 HD and normal subjects and r = −0.559, P

Flagellin subunit A gene (flaA) typing of Campylobacter has been recognized by several groups as a relatively simple and quick genotyping method. The present study aimed to create, for the first time in Greece, a database with flaA restriction patterns, which could be used for future epidemiological and clinical studies. A total of 207 C. jejuni clinical isolates of known serotype were collected from 5 general hospitals of the area of Attica, during the period 2000-2003.The RFLP profiles of each strain were matched in 44 bins of 0 or 1. Thirty nine different flaA types, designated as flaA 1 GR to flaA 39 GR (GR: Greece) were found. There was no significant association of certain genotypes with certain serotypes. However flaA typing showed a remarkable discriminatory ability inside the non-typable (NT) group.Evaluating our results we observed (i) that there was no clonality of a certain flaA type among the strains and the serotypes examined and (ii) that the discriminatory ability of flaA typing was much better than that of serotyping. Giving a simple and detailed description of the data analysis, we are the first who publish the bin patterns for the flaA genotypes found.

Background: Telomerase preserves telomere length and structure, preventing cellular senescence, which is associated with alteration of the chromosomal ends. We hypothesized that telomerase activity is altered in peripheral blood mononuclear cells (PBMCs) of hemodialysis (HD) patients. To investigate this hypothesis as well as the relationship between telomerase and inflammation, we measured the activity of this reverse transcriptase as well as the level of several inflammatory markers in PBMCs and serum of an end-stage renal failure (ESRF) population and a non-renal-failure group of subjects. Methods: In PBMCs isolated from 42 HD and 39 non-renal-failure subjects of the same age (51.0 ± 12.4 and 51.4 ± 12.1 years, respectively) telomerase activity was measured using PCR-ELISA; the method was based on the telomeric repeat amplification protocol. Results: Telomerase activity in PBMCs was detected in 18 (42.9%) HD and 28 (71.8%) non-renal-failure subjects (p = 0.013). Among positive subjects, percent telomerase activity in PBMCs was significantly higher in non-renal- failure (117 ± 112 %) than in HD (47.6 ± 57.1 %) subjects (p = 0.008). Detectable telomerase activity was lower in long-term than in short-term HD patients (13.3 ± 8.9 vs. 75.0 ± 64.8%, respectively, p = 0.015). Although higher in HD group, inflammatory indexes (C-reactive protein, interleukin-6, IL-6, soluble IL-6 and soluble gp130) were not correlated to telomerase activity in PBMCs. Conclusion: Telomerase activity in PBMCs is reduced in HD patients. It seems that, at least in this type of cell in this population, defense from senescence, as assessed by telomerase activity, is altered and associated with the chronicity of uremia/HD procedure.

Background Systemic microinflammation is correlated with atherosclerosis. It needs a reliable assessment. This study explores the temporal variations of three inflammatory indexes [C-reactive protein (CRP), serum amyloid A (SAA) and interleukin-6 (IL-6)] in a period free of clinical events and tests the reliability of their multiple measurements for the assessment of microinflammation in haemodialysis (HD) patients, a population at high risk of atherosclerotic cardiovascular disease. Methods For 4 months, serum CRP, SAA and IL-6 were measured in 29 HD patients during the weeks they were free of inflammatory clinical events (> or =12 measurements for each index in every patient). The components of the variance as well as the reliability of two to five measurements for each index, aimed at assessing microinflammation precisely, were computed. Results The median (interquartile range) of CRP was 2.3 (0.9-4.9) mg/l, of SAA 3.7 (2.1-9.3) mg/l and of IL-6 4.4 (2.2-7.7) pg/ml. Patients were approximately equally distributed between three groups of low, intermediate and high variability for each index. The contribution of intraindividual (biological) variation to the total of variance was 71.3%, 69.3% and 86.7% for CRP, SAA and IL-6, respectively (higher than in all other similar studies in healthy populations). Using two measurements, the estimated reliability was 57-68% for CRP in two-thirds of the patients (comparable with that found in healthy subjects) and 57% for SAA and IL-6 in only one-third of the patients. Increasing the number of measurements up to five did not change the reliability. Conclusions Individual factors significantly influence the levels of inflammatory indexes in HD patients in periods free of inflammatory clinical events. The mean of two weekly CRP measurements, but not of SAA or IL-6, seems to assess microinflammation in most patients with a sufficient reliability.

Background: Inflammation is frequently elevated, and seems to be episodic in hemodialysis (HD) patients. Whether, its episodic character is due to the temporal variability, in periods free of clinical events, of the inflammatory indices or due, to the acute phase response induced by common inflammatory stimuli, has not been investigated yet in a longitudinal study. This study explores inflammation forms, characteristics and causes which are probably related to the high cardiovascular disease (CVD) morbidity in HD patients. Methods: In 37 HD patients, high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and interleukin-6 (IL-6) were weekly measured for 16 consecutive weeks. Inflammatory clinical events, in the week before every measurement, were recorded. Repeated measures ANOVA were applied for statistical analysis. Results: Fifty-one of 533 patient-weeks were positive for a clinical event. Mean ± SD (range) hs-CRP was 7.01 ± 16.06 (0.2–169) mg/l for all the weeks of the study, 38.25 ± 39.35 (2.1–169) mg/l for the weeks with clinical events and 3.70 ± 3.86 (0.2–26.1) mg/l for the weeks free of events. Variations for SAA and IL-6 were similar. ‘Clinical events’ strongly influenced acute-phase proteins and IL-6 levels. The effect of the factor ‘time’ (as assessed by inflammatory indices variation in weekly repeated measurements) was significant for all the 3 indices measured, independently of the factor ‘clinical events’. Conclusions: In periods free of clinical events, microinflammation characterizes HD patients and fluctuates in time. Inflammation due to common clinical events is added, periodically, to this microinflammation. The high level persistent microinflammation as well as the superimposed – due to clinical events – inflammation could be related to the CVD in these patients.

A hundred and twentynine Campylobacter jejuni strains isolated from hospitalized children with gastroenteritis were serotyped by the heat-stable antigen scheme (HS, Penner's method). Isolates belonged to two different periods. Group A contained strains isolated in 1987–1988 and group B contained strains which were isolated in 1998–2000. A variety of serotypes was found. Serotype HS:2 was predominant, followed by the HS:4 complex and HS:1,44. Many clinically important Guillain-Barre Syndrome associated serotypes – like HS:19 – were identified. There were no significant differences in the distribution of serotypes between the two periods. The present report provides reference data, as this is the first C. jejuni serotyping study ever made in Greece.

Objective To investigate the prevalence of class-specific antibodies (IgG, IgA) to Yersinia enterocolitica plasmid-encoded outer proteins (Yops) in patients with diagnosed Hashimoto's thyroiditis. Methods Seventy-one patients with Hashimoto's disease, 464 healthy blood donors and 250 patients with non-postinfectious rheumatic disorders (matched controls) were tested for class-specific antibodies to Yops. Anti-Yop antibodies were determined by ELISA and Western blot. Results The prevalence of class-specific antibodies to Yops as determined by ELISA was 14-fold higher (20 of 71; 28.2%) in people with Hashimoto's thyroiditis than in the two control groups. These results were confirmed by the Western blot, with 16 positive sera, three equivocal and one negative. Conclusions There is strong clinical and seroepidemiologic evidence for an immunopathologic causative relationship between Yersinia enterocolitica infection and Hashimoto's thyroiditis. Further investigation concerning the mechanisms involved and the possible effects of antibacterial chemotherapy on the outcome of Hashimoto's disease is warranted.

Summary Background Fusarium spp. can cause disseminated infections, particularly in immunocompromised patients. Fusarium verticillioides is a human pathogen, and sporadic cases of fusariosis have been reported. Aim To report a nosocomial cluster of F. verticillioides bloodstream infections among seven immunocompetent inpatients following reconstruction works. Methods Identification was performed using macroscopic and microscopic morphology, and molecular assays (sequencing the nuclear ribosomal internal transcribed spacer region and translation elongation factor-1α gene). Susceptibility testing was performed in accordance with the guidelines of the Clinical and Laboratory Standards Institute. Environmental surveillance specimens were taken and cultured on Sabouraud dextrose agar plates. Findings In total, 16 blood cultures obtained from the seven patients were positive for F. verticillioides . All surveillance cultures were negative. Conclusions In order to prevent fungaemia, it is important to implement effective infection control measures, before, during and after demolition and construction activities in healthcare settings.

Background Diagnostic errors can occur, in infectious diseases, when anti-microbial immune responses involve several temporal scales. When responses span from nanosecond to week and larger temporal scales, any pre-selected temporal scale is likely to miss some (faster or slower) responses. Hoping to prevent diagnostic errors, a pilot study was conducted to evaluate a four-dimensional (4D) method that captures the complexity and dynamics of infectious diseases. Methods Leukocyte-microbial-temporal data were explored in canine and human (bacterial and/or viral) infections, with: (i) a non-structured approach, which measures leukocytes or microbes in isolation; and (ii) a structured method that assesses numerous combinations of interacting variables. Four alternatives of the structured method were tested: (i) a noise-reduction oriented version, which generates a single (one data point-wide) line of observations; (ii) a version that measures complex, three-dimensional (3D) data interactions; (iii) a non-numerical version that displays temporal data directionality (arrows that connect pairs of consecutive observations); and (iv) a full 4D (single line-, complexity-, directionality-based) version. Results In all studies, the non-structured approach revealed non-interpretable (ambiguous) data: observations numerically similar expressed different biological conditions, such as recovery and lack of recovery from infections. Ambiguity was also found when the data were structured as single lines. In contrast, two or more data subsets were distinguished and ambiguity was avoided when the data were structured as complex, 3D, single lines and, in addition, temporal data directionality was determined. The 4D method detected, even within one day, changes in immune profiles that occurred after antibiotics were prescribed. Conclusions Infectious disease data may be ambiguous. Four-dimensional methods may prevent ambiguity, providing earlier, in vivo, dynamic, complex, and personalized information that facilitates both diagnostics and selection or evaluation of anti-microbial therapies.

G. Papadakis , N.A. Okoba , C. Nicolaou , F. Boufidou , A. Ioannidis , S. Bersimis , Doctors of the World e Greece, S. Chatzipanagiotou * Greek Delegation of Doctors of the World, Athens, Greece Department of Medical Biopathology, Eginition Hospital, Medical School, University of Athens, Athens, Greece Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Greece Department of Statistics and Insurance Science, University of Piraeus, Piraeus, Greece

Patients suffering from renal failure exhibit an impaired immune system function. We wanted to investigate the transcription of the tumor suppressor genesp53andRBto record, if these cells could be stimulatedin vitroin order to divide, after the addition of antigenic and inflammatory factors. This expression was measured by real-time PCR in peripheral blood mononuclear cells (PBMCs) from three different groups: ten healthy individuals, ten patients with chronic kidney disease (CKD), and ten dialysis patients with end stage renal disease (ESRD). The transcription rate of these genes was also measured after the cultivation of PBMCs under four different conditions: just with the culture medium, with lipopolysaccharide (LPS), with C-reactive protein (CRP), and with lipoxin A4(LXA4)-LPS. Our results show that in most cases after the cultivation with additives, the transcription levels were higher in dialysis patients compared to those of the other two groups. Our findings serve as indications of cellular senescence on a molecular level, while it seems that these cells are less easily stimulatedin vitroin order to duplicate.

Background: Campylobacter spp. are together with Salmonella spp. the leading causes of human bacterial gastroenteritis worldwide. The most commonly isolated species in humans are Campylobacter jejuni and C. coli. The isolation, identification, and antimicrobial resistance of Campylobacter spp. from poultry and raw meat from slaughterhouses, has been investigated for the first time in Greece. During the period from August 2005 to November 2008 a total of 1080 samples were collected: (a) 830 fecal samples from five poultry farms, (b) 150 cecal samples from chicken carcasses in a slaughterhouse, and (c) 100 fecal samples from one pig farm near the region of Attica. The identification of the isolates was performed with conventional (sodium hippurate hydrolysis and commercial identification system (Api CAMPY system, bioMerieux, France), as well as with and molecular methods based on 16S rRNA species specific gene amplification by PCR and subsequent sequence analysis of the PCR products. Results: Sixteen Campylobacter strains were isolated, all collected from the poultry farms. None of the strains was identified as C. jejuni. Antimicrobial susceptibility to six antimicrobials was performed and all the strains were susceptible to ciprofloxacin, amoxicillin–clavulanic acid, and gentamicin. Thirteen out of 14 C. coli were resistant to erythromycin and all C. coli strains were resistant to ampicillin. Conclusion: Our results emphasize the need for a surveillance and monitoring system with respect to the prevalence and antimicrobial resistance of Campylobacter in poultry, as well as for the use of antimicrobials in veterinary medicine in Greece.

The antimicrobial susceptibility of 129 Campylobacter jejuni strains, isolated from hospitalized children with gastroenteritis, to five antimicrobials, including nalidixic acid, ciprofloxacin, erythromycin, ampicillin and co-amoxiclav, was determined. Isolates belonged to two time periods: group A contained strains isolated in 1987-1988; and group B 1998-2000. Antimicrobial susceptibility patterns differed significantly between the two groups with respect to quinolones, with an increase in the percentage of resistant strains in group B (30.6% versus 0% in group A), whereas erythromycin, ampicillin and co-amoxiclav were effective drugs in both groups.

Low and not high cholesterol seems to predict high mortality in hemodialysis (HD) patients. The confirmation of this reverse epidemiology as well as its possible interconnection with the increased inflammatory activity observed in this population is being explored in the present study. A group of 136 HD patients was prospectively studied for 2 years, and cardiovascular disease (CVD) as well as all-cause mortality and morbidity were recorded. Baseline lipid profile, inflammatory status, and patients' characteristics were studied as potential survival and hospitalization predictors. During the 24-month follow-up, 21 deaths (52.4% due to CVD) and 38 hospitalizations (55.3% due to CVD) were recorded. In multivariate Cox regression analysis, decreased interleukin-10 (IL-10) and decreased total serum cholesterol (TChol) were the only independent predictors of CVD mortality while C-reactive protein and decreased TChol predicted all-cause mortality. Interleukin-10 at baseline was 11.29 +/- 21.49 vs. 5.51 +/- 4.57 pg/mL (P0.018) and TChol 167.37 +/- 47.84 vs.122.04 +/- 26.48 mg/dL (P0.000) in survivors vs. nonsurvivors from CVD, while C-reactive protein at baseline was 9.37 +/- 11.54 vs. 23.15 +/- 18.76 mg/L (P0.000) and TChol 169.26 +/- 46.42 vs. 133.26 +/- 46.33 mg/dL (P0.003) in survivors vs. nonsurvivors from any cause of death. Using the same method of statistical analysis, IL-6 and decreased soluble gp130 (sgp130)--an antagonist of IL-6 action--were found to be the only independent prognostic factors for hospitalization due to CVD while decreased soluble gp130 remained the sole predictor of hospitalization due to any cause. In conclusion, reverse epidemiology regarding cholesterol is confirmed in the present study. Furthermore, inflammatory activity also predicts, independently of or in conjunction with low-cholesterol, CVD and all-cause morbidity and mortality in HD patients.

Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver disease. The aim of the present study was to investigate the possible correlation, between liver dysfunction biological markers and vitamin B12, with interleukin-6, in the serum of alcohol-dependent individuals without liver disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males and 10 females) treated on an inpatient basis according to a standard detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT, gamma-GT), as well as the concentration of B12 and IL-6, were determined on admission. A strong positive correlation has been observed between IL-6 and B12, ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The results confirmed that in alcohol-dependent individuals, the median serum concentration of IL-6, before the beginning of the treatment, had a significant positive correlation with the liver dysfunction biological markers and B12. In conclusion, IL-6 might be used as an additional diagnostic marker for the degree of liver dysfunction in alcohol dependent individuals.

A total of 170 Campylobacter jejuni strains isolated from the stool of children with clinical gastroenteritis, aged from 3 months to 14 years, were collected during a two-year period (2004-2005). From the 170 strains 30% were resistant to ciprofloxacin (MIC > or = 4 microg/ml), 55% to tetracycline (MIC > 8 microg/ml), 13% to clindamycin (MIC > or = 8 microg/ml), 4% to ampicillin (MIC > 16 microg/ml), 6% to erythromycin (MIC > or = 8 microg/ml), 4% to coamoxiclav (MIC > or = 16/8 microg/ml) and 0% to gentamicin. Compared to previous reports from Greece, the antimicrobial resistance rates to erythromycin, ampicillin and coamoxiclav remain low, while they are still high for tetracycline and ciprofloxacin. Considering similar reports from many other countries and the high incidence of Campylobacter gastroenteritis worldwide, the value of ciprofloxacin as a first choice drug in the empiric treatment of the infection is questionable.

SUMMARY: Background: Infectious agents may be implicated in the inflammatory atherosclerotic process. Not only specific microorganisms but also the infectious burden, defined as the number of pathogens to which a patient is exposed, has been associated with atherosclerosis. In the present study, the infectious burden, determined directly (by identification of viable pathogens in peripheral blood mononuclear cells (PBMC)) and indirectly (by serum antibodies detection) is correlated to the inflammatory and atherosclerotic status in haemodialysis (HD) patients, a population at high risk for cardiovascular disease. Methods: The viable forms of four microorganisms ( Chlamydia pneumoniae , herpes virus 1 and 2 and cytomegalovirus) were identified in patients PBMC by cell cultures and subsequent polymerase chain reaction. Serum IgG against the above pathogens and Helicobacter pylori were also determined. Inflammation was assessed by measurement of C-reactive protein (CRP), serum amyloid A (SAA), three pro- and one anti-inflammatory cytokines and four adhesion molecules. Atherosclerosis was defined by a scoring system using medical history data. Results: The number of viable pathogens identified in PBMC in the 122 HD patients included in the study were zero in 22.1% of them, one in 33.6%, two in 43.4% and three in one patient. The number of IgG antibodies determined was one in 6.6% of patients, two in 32%, three in 48.4% and four in 13.1%. Seropositivity was not significantly different between patients with or without the respective viable pathogen identified in PBMC. Atherosclerosis was present in 40.2% of patients, and CRP, SAA and interleukin-6 were all increased in these patients. Neither inflammatory indexes nor atherosclerosis were significantly different in patients with a higher number of viable pathogens detected in PBMC or in those with a higher antibodies number. Conclusions: The direct infectious burden determination (the number of viable pathogens in PBMC) does not coincide with the serum (by IgG detection) infectious burden. Although inflammation correlates to atherosclerosis, neither PBMC nor the serum infectious burden is associated with these two entities in the inflamed and atherosclerotic HD patients.

Background: A reverse association between cholesterol level and cardiovascular disease mortality is observed in hemodialysis (HD) patients; this paradoxical relationship may be explained by the coexistence of inflammation. Interleukin-6 (IL-6) is a central regulator of inflammation; its action is augmented by the soluble IL-6 receptor (sIL-6R) and inhibited by the soluble gp130 (sgp130). In order to investigate the potential association of inflammation with cholesterol levels in the HD population, release of soluble IL-6 components by peripheral blood mononuclear cells (PBMCs) was measured in two groups of HD patients with distinctly different lipid profile and in a control group. Methods: Twenty-two HD patients with low serum cholesterol (range 85–171 mg/dl), 23 HD patients with high cholesterol (189–342 mg/dl) and 21 normolipidemic non-renal failure subjects were enrolled in the study. IL-6, sIL-6R and sgp130 were measured by ELISA in the serum and in the supernatant collected from cell cultures of activated or resting PBMCs isolated from all three groups. Results: Serum IL-6 and sgp130 level was higher while sIL-6R was lower in both groups of HD patients compared to the control group. The ex-vivo release of the IL-6 and sgp130 by unstimulated PBMCs did not differ significantly between the three groups but that of the sIL-6R was higher in non-renal failure than in hypercholesterolemic HD subjects. Production of sIL-6R by stimulated PBMCs was higher in low-cholesterol HD patients (p < 0.001) and the same was valid for the sgp130 release (p = 0.034). Release of IL-6 by activated PBMCs was higher in the low-cholesterol compared to the high-cholesterol HD patients group (p = 0.011 for post hoc test). Major serum lipid fractions were inversely correlated to IL-6 and sIL-6R production from stimulated PBMCs in HD but not in non-renal failure subjects. Finally, release of the sgp130 by PBMCs was significantly reduced in 13 hypertriglyceridemic – and hypercholesterolemic – HD patients. Conclusion: Production of soluble components of a crucial pro-inflammatory and potentially atherogenic cytokine, namely the IL-6, by stimulated PBMCs appears to be inversely correlated with the serum cholesterol levels in HD patients.

Whipple disease is a relapsing systemic illness caused by Tropheryma whippelii. Central nervous system involvement occurs in 5%-40% of all patients. Hypothalamic manifestations occur in 31% of Whipple encephalopathy, including polydipsia, hyperphagia, change in libido and insomnia. We report a case of a 48-year-old man with severe insomnia, depression, dementia, dysarthria, myoclonic movements of the limbs and ophthalmoplegia. The diagnosis of Whipple encephalopathy was confirmed by PCR analysis of blood and faeces. He received a full dose of antibiotic treatment. Despite clinical improvement, resolution of the lesions detected in MRI scan of the brain and negative results of the PCR in blood, faeces and cerebrospinal fluid six months later, insomnia persisted and finally subsided after the administration of carbamazepine (600 mg/day). Our case supports the finding that carbamazepine might be useful in the treatment of insomnia associated with Whipple encephalopathy.

IL-6 acts on target cells via the ligand-binding protein interleukin-6 receptor (IL-6R) and the affinity-converting and signal-transducing glycoprotein 130 (gp130). Soluble interleukin-6 receptor (sIL-6R) has an agonistic role because the soluble complex (IL-6/sIL-6R) can activate cells that do not express IL-6R and an antagonistic role as it enhances the inhibitory activity of sgp130. Soluble forms of both receptors, sIL-6R and sgp130, regulate the action of IL-6. sIL-6R was measured by a sensitive enzyme-linked immunosorbent assay in paired sera and cerebrospinal fluid (CSF) from 46 patients with inflammatory neurological diseases (IND), 45 patients with relapsing-remitting multiple sclerosis (RR-MS), 13 patients with primary progressive multiple sclerosis (PP-MS), 17 patients with other non inflammatory neurological diseases (NIND) and 13 mentally healthy individuals--healthy controls (HC). Patients with RR-MS had CSF sIL-6R levels comparable to those from patients with IND, but higher than patients with NIND and HC. A positive correlation between the CSF/serum albumin (QAlb) and CSF sIL-6R levels was observed in IND but not in RR-MS patients indicating that CSF sIL-6R levels in IND patients could be influenced by serum sIL-6R and blood brain barrier (BBB) permeability properties. RR-MS patients had higher values of [CSF/serum sIL-6R:CSF/serum albumin] (sIL-6R index) than IND patients suggesting that in multiple sclerosis (MS), the increase in CSF sIL-6R could be due to intrathecal synthesis of sIL-6R. The finding of increased CSF sIL-6R concentrations (>979 pg/ml) with sIL-6R index (>4.66), in correlation with positive oligoclonal bands in RR-MS patients, suggests that values of sIL-6R index > 4.66 indicate intrathecal increase of sIL-6R and might be used as an indicator of neuroimmunoregulatory and inflammatory processes in the central nervous system (CNS).

Background. Chlamydia pneumoniae has been implicated as an inflammatory agent in atherosclerosis. Clinical studies in this field have yielded conflicting results, which may have resulted from a lack of standardization for C.pneumoniae detection. We attempted to accurately estimate C.pneumoniae prevalence and to examine whether C.pneumoniae is associated with atherosclerosis and inflammation in haemodialysis (HD) patients. To do this, we assessed C.pneumoniae presence by a combination of methods and correlated its levels with inflammatory and atherosclerotic indexes in these patients. Methods. Chlamydia pneumoniae was identified by polymerase chain reaction (PCR) in DNA extracted from cell cultures inoculated with patient buffy coats and by serum IgG antibodies against C.pneumoniae (IgGCp). Inflammation was assessed by C-reactive protein and serum amyloid A and atherosclerosis was evaluated from clinical and laboratory data. Results. Of the 130 patients, only nine had viable C.pneumoniae in peripheral blood mononuclear cells (PBMCs) while 64 had serum IgGCp. Although patients with viable C.pneumoniae had higher atherosclerotic scores, seropositive and negative patients showed similar scores. Patients with atherosclerosis exhibited higher inflammatory indexes. Neither patients with detectable C.pneumoniae in PBMCs nor seropositive subjects had higher inflammation than negative patients. Conclusions. We found that viable C.pneumoniae in PBMCs, assessed by cell culture and PCR, was present in a small percentage of HD patients and was correlated with atherosclerosis. Seropositivity was much higher in HD patients but was not associated with viable C.pneumoniae or with atherosclerosis. Further studies in HD patients using high sensitivity and specificity methods in larger populations will be necessary to clarify the relationship between C.pneumoniae and atherosclerosis.

To the Editor: In their study, Pupim et al1 show that patients with end-stage renal failure (ESRF) in the highest quartile of C-reactive protein (CRP) and interleukin-6 (IL-6) before hemodialysis (HD) initiation have a significant decrease in the serum level of both markers after 12 months of HD treatment. The baseline levels for IL-6 and CRP in these subgroups were about 58 pg/mL and 62 mg/L, respectively. As the authors note, no exclusion criteria were used for enrollment in the study. These CRP and IL-6 serum levels are probably indicative of an infection or other cause of "real inflammation" (trauma, malignancy, etc.). In the referred study microinflammation investigation is warranted. It is low-grade inflammation that is correlated to atherosclerosis or other threatening processes. Recently, a cut-off for CRP (10 mg/L) indicative for inflammation versus microinflammation was established for the general population2. We also found a similar cut-off for CRP and IL-6 (9.5 mg or pg/L) indicative for an inflammatory clinical event, in a group of HD patients3. Possibly this cut-off is higher in other HD patients, but, as the results in the majority of studies with ESRF patients show, it seems improbable to be higher than 15 mg/L for the CRP.