Nonalcoholic fatty liver disease as a risk factor for Clostridium difficile-associated diarrhea.

AIMS: Clostridium difficile is the most common cause of infectious nosocomial diarrhea among adults in developed countries. Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease and it is associated with bacterial infections. Our goal was to assess whether NAFLD considered a risk factor for C. difficile-associated diarrhea (CDAD). METHODS: We conducted a retrospective study of patients admitted with CDAD at Baruch Padeh Medical Center, Poria, Israel during a period of four years. Data on demographic characteristics, clinical signs, underlying conditions, presence of fatty liver based on computed tomography/ultrasonography imaging and several risk factors for CDI were collected. The control group included patients with diarrhea who were negative for CDT and had been hospitalized during the same period. The controls were matched for age (±5 years) and gender. RESULTS: Totally, 115/164 patients with CDAD met the inclusion criteria. The control group was consisted of 115 hospitalized patients with non-CDAD. The mean age of all the participants (230) was 69.57 ± 18 years. NAFLD was found in 76/115 (66%) patients with CDAD vs. 35/115 (30.4%) in the control group, P < 0.001. Moreover, we found significant associations between CDAD group and metabolic syndrome, prior use of antibiotic in the last 3 months, NAFLD and high serum levels of C-reactive protein. Multivariate analysis showed that NAFLD, odds ratio 1.51, 95% confidence interval 1.2-1.95, P = 0.05 was significantly associated with CDAD. CONCLUSIONS: This retrospective study showed that NAFLD is a risk factor for CDAD. Moreover, metabolic syndrome and high serum levels of C-reactive protein were significantly associated with the risk of CDAD.

Influenza virus and atherosclerosis.

Influenza viruses infect the upper respiratory system, causing usually a self-limited disease with mild respiratory symptoms. Acute lung injury, pulmonary microvascular leakage and cardiovascular collapse may occur in severe cases, usually in the elderly or in immunocompromised patients. Acute lung injury is a syndrome associated with pulmonary oedema, hypoxaemia and respiratory failure. Influenza virus primarily binds to the epithelium, interfering with the epithelial sodium channel function. However, the main clinical devastating effects are caused by endothelial dysfunction, thought to be the main mechanism leading to pulmonary oedema, respiratory failure and cardiovascular collapse. A significant association was found between influenza infection and acute myocardial infarction (AMI). The incidence of admission due to AMI during an acute viral infection was six times as high during the 7 days after laboratory confirmation of influenza infection as during the control interval (10-fold in influenza B, 5-fold in influenza A, 3.5-fold in respiratory syncytial virus and 2.7-fold for all other viruses). Our review will focus on the mechanisms responsible for endothelial dysfunction during influenza infection leading to cardiovascular collapse and death.

Detection and characterization of carbapenemase-producing Enterobacteriaceae in wounded Syrian patients admitted to hospitals in northern Israel.

Since 2013, four hospitals in northern Israel have been providing care for Syrian nationals, primarily those wounded in the ongoing civil war. We analyzed carbapenemase-producing Enterobacteriaceae (CPE) isolates obtained from these patients. Isolate identification was performed using the VITEK 2 system. Polymerase chain reaction (PCR) was performed for the presence of bla KPC, bla NDM, and bla OXA-48. Susceptibility testing and genotyping were performed on selected isolates. During the study period, 595 Syrian patients were hospitalized, most of them young men. Thirty-two confirmed CPE isolates were grown from cultures taken from 30 patients. All but five isolates were identified as Klebsiella pneumoniae and Escherichia coli. Nineteen isolates produced NDM and 13 produced OXA-48. Among a further 29 isolates tested, multilocus sequence typing (MLST) showed that ST278 and ST38 were the major sequence types among the NDM-producing K. pneumoniae and OXA-48-producing E. coli isolates, respectively. Most were resistant to all three carbapenems in use in Israel and to gentamicin, but susceptible to colistin and fosfomycin. The source for bacterial acquisition could not be determined; however, some patients admitted to different medical centers were found to carry the same sequence type. CPE containing bla NDM and bla OXA-48 were prevalent among Syrian wounded hospitalized patients in northern Israel. The finding of the same sequence type among patients at different medical centers implies a common, prehospital source for these patients. These findings have implications for public health throughout the region.

[The secondary prevention of osteoporosis needs a multidisciplinary approach]. / La prévention secondaire de l'oséoporose passe par un circuit multidisciplinaire.

Enormous burden for our aging population and health care system, the hip fracture remains a major challenge to public health. Every year, there are over 15.000 hip fractures in Belgium. Nonetheless of the technical progress in surgery and the follow-up for, postoperation, the morbidity linked to this affection remains important because the vast majority of the patients will not recovered their previous autonomy after the fracture. The mortality is also high. Although it represents 14 % of the total osteoporotic fractures, the hip fractures account for 92 % of the costs caused by the disease, corresponding to 150.000.000 euros per year in Belgium. The present demographic evolution suggests that this amount will increase by 7 fold in 2050. Different epidemiological studies show that a large proportion of these fractures should have been avoided if the reason of the bone fragility, osteoporosis, had been previously diagnosed and treated. In this context, since several years, an increasing number of clinical paths - the Fracture Liaison Services (FLS) - have emerged all over the world. Brugmann Hospital has decided to implement such a model - focusing, by a systematic approach, to better connection and communication between available healthcare resources.

Performance of Gram staining on blood cultures flagged negative by an automated blood culture system.

Blood is one of the most important specimens sent to a microbiology laboratory for culture. Most blood cultures are incubated for 5-7 days, except in cases where there is a suspicion of infection caused by microorganisms that proliferate slowly, or infections expressed by a small number of bacteria in the bloodstream. Therefore, at the end of incubation, misidentification of positive cultures and false-negative results are a real possibility. The aim of this work was to perform a confirmation by Gram staining of the lack of any microorganisms in blood cultures that were identified as negative by the BACTEC™ FX system at the end of incubation. All bottles defined as negative by the BACTEC FX system were Gram-stained using an automatic device and inoculated on solid growth media. In our work, 15 cultures that were defined as negative by the BACTEC FX system at the end of the incubation were found to contain microorganisms when Gram-stained. The main characteristic of most bacteria and fungi growing in the culture bottles that were defined as negative was slow growth. This finding raises a problematic issue concerning the need to perform Gram staining of all blood cultures, which could overload the routine laboratory work, especially laboratories serving large medical centers and receiving a large number of blood cultures.

[Gout, revisited]. / La goutte, revisitée.

In recent decades, gout became the most common inflammatory arthritis and one in which pathogenesis and risk factors are best understood. One of the treatment objectives in current guidelines is "cure". However, audits show that minority of patients with gout receive adequate advice and treatment. Doctors often focus on managing acute attacks rather than viewing gout as a chronic progressive crystal deposition disease. Accordingly, urate-lowering treatment is underprescribed and often underdosed. The recent introduction of a panel of new treatments of gout and a better understanding of epidemiologic factors (such as the fructose) may improve management of this easily diagnosed and curable form of potentially severe arthritis, worsening probably the cardiovascular prognostic.

[Ultrasonography and rheumatology]. / L'échographie dans la pratique rhumatologique.

Muskuloskeletal ultrasound has been incorporated by rheumatologist to the clinical practice over the past decade. The technical improvements of the devices allowed the production of high quality images contributing to better identification of joint inflammation and structural damage. In this review, we highlight the applications of ultrasound in the study of different rheumatic conditions.

BACTEC FX system as a tool for culturing gastric biopsies and Helicobacter pylori diagnosis.

Helicobacter pylori infection represents a key factor in the etiology of various gastrointestinal diseases. There are several acceptable methods to identify this microorganism. Some are invasive and some are noninvasive. This study demonstrates the use of BACTEC FX system for the growth and diagnosis of H. pylori isolated from gastric biopsy specimens, cut and placed in blood culture bottles, with subsequent incubation in the apparatus. Twenty-five positive and 15 negative biopsy samples tested using the quick urease technique, CUTest, were collected from 40 patients with confirmed chronic gastric inflammation. The biopsy samples were manually cut using a sterile scalpel and placed in tubes containing 5 ml of fetal bovine serum. The resulting suspensions were transferred using a syringe into anaerobic blood culture bottles. These bottles were incubated at 35 °C for a period of 7 days in the BACTEC FX system. All biopsy samples that reacted positive to the CUTest and one biopsy sample that reacted negative to the CUTest were confirmed as positive by the BACTEC FX system. In addition, there was a correlation between the positive culture and histology examination results. The use of BACTEC FX system significantly shortens the time needed for culturing, which makes the system more efficient in the identification of H. pylori. It should be emphasized that performing microbial culture testing has a significant role in monitoring antibiotic resistance, which cannot be done using other existing methods for H. pylori diagnosis.

Protective effect of the immunomodulator AS101 against cyclophosphamide-induced testicular damage in mice.

BACKGROUND: Cyclophosphamide (Cy), a widely used anticancer drug, is associated with significant testicular damage and sterility. Co-administration of the immunomodulating compound AS101 during chemotherapy treatments was previously shown to protect organs against cytotoxic damage, without attenuating the drug's anticancer effect. In this animal study, we investigated the effect of AS101 on testicular damage, sperm DNA damage and infertility induced by Cy. Akt and glycogen synthase kinase-3beta (GSK-3beta) phosphorylation were investigated as a possible chemoprotective mechanism. METHODS: Mature male mice, 10 in each group, were injected intraperitoneally with 200 mg/kg Cy once a week for 5 weeks, with or without concurrent treatment with 10 microg per mouse AS101 three times per week. Damage to testicular tubules and sperm production was determined, sperm chromatin damage was analyzed and fertility was gauged. Akt and GSK-3beta phosphorylation were evaluated. RESULTS: Co-treatment with AS101 during the course of Cy administration significantly reduced the percentage of damaged seminiferous tubules (76.0 +/- 10.8% versus 40.3 +/- 2.6%), and reduced sperm DNA fragmentation (%DFI) from 44.7 +/- 1.0% to 25 +/- 6.5%. Co-treatment with AS101 also partially protected against the decrease in numbers of impregnated females and litter size. AS101 increased Akt and GSK-3beta phosphorylation. CONCLUSIONS: Our results indicate that AS101 can significantly protect against Cy-induced testicular damage and sperm DNA damage, probably by acting through Akt/GSK-3beta phosphorylation.

[The effectiveness of glass bead sterilizer in the dental practice].

OBJECTIVES: Although it is not FDA-approved as inter-patients sterilization measure, in Israel, glass bead sterilizer is still a common method for chair-side sterilization of small dental hand instruments, especially endodontic files. Studies from the 1950-1970s achieved sterilization by the bead sterilizer within few seconds. Nevertheless, there are no current evidence-based instructions for using this sterilizer. The study was designed to evaluate the effectiveness of this method in sterilization of endodontic files, according to current microbiologic knowledge. METHODS: Standard endodontic k-files (#15, 50, 80) were sterilized in a steam autoclave and then soaked in Actinomyces israelii, Eikenella corrodens or Bacillus cereus [0.5 MacFarland] media for 10 sec. After drying, the files were placed in 225 degrees C or 250 degrees C-heated glass bead sterilizers for 0, 15, 30 or 60 sec. After appropriate incubation for 10 d, morphologic and biochemical examinations were performed to reveal bacterial growth. RESULTS: Files that have been contaminated with A. israelii were sterilized within 30 sec, whereas B. cereus and E. corrodens-contaminated files needed 60 sec for sterilization. CONCLUSIONS: The use in bead sterilizer has to be limited only for sterilization of intra-appointment purpose. However, it seems that the common method of using bead sterilizer for sterilization time of few seconds is not effective. In order to eliminate spore-forming bacteria, like B. cereus, by bead sterilizer, the sterilization time has to be at least 60 sec. More research is needed, however, for establishing the effectiveness of the bead sterilizer for viral infection control and for other dental instruments.

Thrombotic markers in metabolic syndrome subjects exposed to diesel exhaust.

Traffic-derived particulate matter (PM) is associated with cardiovascular morbidity and mortality, but the mechanism of this association is unclear. Prothrombotic processes have been linked to PM in epidemiological and animal models, but have not been consistently implicated in controlled human models. Diesel exhaust (DE) is a major contributor to PM. We conducted a controlled human exposure of DE in subjects with metabolic syndrome. The study objective was to evaluate DE exposure effects on prothrombotic markers in a population vulnerable to cardiovascular disease. A randomized, crossover, double-blinded design was used: 16 subjects with metabolic syndrome exposed on 3 different days (> or = 2 wk washout) to DE at 0 (filtered air, FA), 100 microg PM(2.5)/m(3) (DE(100)) and 200 mug PM(2.5)/m(3) (DE(200)). We assessed DE-associated changes in D-dimer, von Willebrand factor (VWF), and plasmin activator inhibitor-1 (PAI-1) at 3, 7, and 22 h after exposure initiation. A DE(200)-attributable decrease (1.17-fold; CI 1.04 to 1.34) in VWF was noted at 7 h. Significant changes did not occur in other primary endpoints. As previously noted with healthy subjects, strong diurnal patterns in PAI-1 were observed. Thus, in a novel study, we were unable to demonstrate a prothrombotic effect of moderate-dose diesel exhaust exposure in a population at risk for cardiovascular disease.

[Inflammatory low back pain]. / La lombalgie inflammatoire.

Low back pain is a frequent symptom to consult the general practioner or the osteo-articular specialist. It is important to identify patients with inflammatory back pain (5 to 10 %) because the management and the treatment are different. Spondylarthropathies, especially ankylosing spondylitis (AS) are the most frequently encountered. The inflammatory characteristics of pain give clues for the diagnosis and allow to make appropriate management. Biological tests and imaging from X rays to MRI are used. As therapy is primarily based on NSAID use, in case of unsatifactory response in peripheral arthritis, disease modyfing drugs such as salazopyrine and methotexate (MTX) are used. Anti TNF are used in AS patients unresponsive to previous therapy (infliximab, etanercept, adalimumab) with a response in 50% of the patients. Etanercept is however not indicated in patients with uveitis.

Low back pain as presenting manifestation of giant cell arteritis associated to abdominal aortitis.

Giant cell arteritis (GCA) is the most common vasculitis in Western countries in individuals over the age of 50. The diagnosis is relatively straightforward when typical features, such as headache, jaw claudication or other ischemic complications are present. Although atypical presentations of GCA have been described, herein we report for first time low back pain as the presenting manifestation of this vasculitis. We also emphasize the importance of considering the use of positron emission tomography (PET) in the evaluation of GCA patients presenting without "overt" cranial ischemic manifestations.

The neural correlates of understanding the other's distress: a positron emission tomography investigation of accurate empathy.

The purpose of the present study was to assess the relationship between brain metabolism and empathic response. Six right-handed healthy volunteers were scanned with PET and fluorodeoxyglucose twice: during an interview about neutral story themes and during an empathic response eliciting interview about a story of a character in distress. Metabolic values in the medial and superior frontal gyrus, occipitotemporal cortices, thalamus and the cerebellum were higher during empathic response than during the neutral theme interview. Furthermore, the subjects' empathy scores were positively correlated with metabolism in the medial aspects of the superior frontal gyrus. Our results suggest that empathy consists of both affective and cognitive components and hence may involve cortices that mediate simulation of emotional processing and mental state attribution.

Long-term tolerability of tramadol LP, a new once-daily formulation, in patients with osteoarthritis or low back pain.

INTRODUCTION: Tramadol hydrochloride is a centrally acting analgesic, which possesses opioid agonist properties and activates monoaminergic spinal inhibition of pain. An oral, once a day, sustained release formulation of tramadol is thought to be advantageous compared with immediate release preparations as it prevents plasma peaks associated with increased side-effects of the drug. It may also improve compliance. The purpose of the study was to assess the long-term safety of a new sustained-release formulation of tramadol (tramadol LP) in patients with knee or hip osteoarthritis and in patients with refractory low back pain. STUDY DESIGN: The design was a phase III, open, multicentre, international, tolerability study with tramadol LP at a dose titrated by the patient between 100 and 400 mg once daily, according to the intensity of pain. The treatment was administered for a continuous period of 4 weeks followed by an intermittent intake of 5 months in 204 patients. The safety criteria for evaluation were recording of adverse events, laboratory tests, electrocardiogram, radiography, global tolerability assessed by the patient and the investigators. RESULTS: Long-term use of tramadol LP was reasonably well tolerated. Most of the reported adverse events were expected and occurred within the first month of treatment. Roughly half of the patients (49%) reported adverse events, of which 66% were related to treatment. Gastrointestinal events (nausea and vomiting) were the most frequent. Serious adverse events were reported in 6.4% of patients, from which only two cases were related to treatment. There was no sign of tolerance development and the percentage of patients presenting withdrawal symptoms after the end of treatment was low (6%). CONCLUSION: Long-term treatment with tramadol LP once daily is generally safe in patients with osteoarthritis or refractory low back pain.

A dose adjustment in patients with rheumatoid arthritis not optimally responding to a standard dose of infliximab of 3 mg/kg every 8 weeks can be effective: a Belgian prospective study.

OBJECTIVES: To analyse the effect of a dose increase in patients with severe rheumatoid arthritis (RA) with insufficient clinical response to 3 mg/kg infliximab every 8 weeks. METHODS: Patients suffering from active refractory RA despite methotrexate, were treated with i.v. infusions of infliximab (3 mg/kg) on week 0, 2, 6 and every 8 weeks thereafter. Based on the clinical judgement at week 22, patients received a dose increase of 100 mg from week 30 on. The American College of Rheumatology (ACR) core set for disease activity measures was regularly assessed. RESULTS: Five hundred and eleven RA patients were included. At week 22, 61.4, 34 and 14.1% of all patients met ACR 20, ACR 50 and ACR 70 criteria, respectively, and 6.1% of patients were in remission. A low swollen joint count at baseline was correlated with improvement at week 22 for ACR 20 (P < 0.06), ACR 50 (P < 0.06) and ACR 70 (P < 0.005). The change in HAQ score between weeks 0 and 22 was predictive for response at week 54 (P < 0.01). The dose of infliximab was increased by 100 mg in 22% of the patients. Most baseline values of patients requiring dose increase were higher (P < or = 0.001) than the baseline values of the remaining patients. Increasing the dose of infliximab by one vial from week 30 on could circumvent the partial loss of response in these patients. CONCLUSION: Infliximab use in this large out-patient cohort resulted in a significant clinical improvement. A subgroup that partially lost response during the first 22 weeks could regain response by adding 100 mg of infliximab to the subsequent doses. Due to the current study design, however, a regression to the mean like effect could not be ruled out.

Is the WKL1 gene associated with schizophrenia?

A missense mutation Leu309Met in the WKL1 (MLC1, KIAA0027) gene, mapped to 22q13.3, was reported to co-segregate with periodic catatonic schizophrenia (SCZ) in a single large German pedigree with seven affected individuals (Meyer et al. [2001: Mol Psychiatry 6:302-306]). This report raised the following questions that were dealt with in the present study: does the Leu309Met mutation have a role in SCZ, or only in catatonic SCZ? Does the mutation Leu309Met in the WKL1 gene, encoding a putative membrane protein, non-selective cation channel, have any effect on the channel activity? Is the WKL1 gene, which is expressed exclusively in brain, expressed differently in SCZ brains compared to controls? These questions were answered by screening the Leu309Met mutation in 117 Israeli Jewish patients with SCZ (55 Ashkenazi and 62 non-Ashkenazi Jews) and 176 matched controls. In search of differences in the level of WKL1 gene expression, postmortem dorsalateral prefrontal cortex of 16 schizophrenic patients and 15 controls was checked. We also measured the putative channel activity of normal WKL1 subcloned in pcDNA3 to determine the effect of the reported Leu309Met mutation. Our results argue against the involvement of WKL1 in SCZ susceptibility.

Uveitis management: a multidisciplinary approach to assess systemic involvement and side effects of treatments.

OBJECTIVE: Non-infectious uveitis is often associated with systemic diseases severe enough to require corticosteroids (CS) and immunosuppressive drugs, which have potential serious side effects. METHODS: 28 patients with non-infectious uveitis were referred by the ophthalmologist. RESULTS: A systemic disease was found in 17/28 patients (60%): sarcoidosis in 11, spondylarthropathy in 3, Behcet's disease in 2, Crohn's disease in 1 patient. Eighteen patients received CS, 21 patients received immunosuppressive drugs. Most side effects were due to CS treatment: Cushing's syndrome in 12, cataract in 11, glucose intolerance in 3, gastric ulcus in 1, hypertension in 1, osteoporosis in 17, avascular bone necrosis in 3 patients. Prophylaxis or treatment of corticosteroids induced osteoporosis consists in calcium, 500 mg/day and vitamin D 400 IU in most of them with in addition hormone replacement therapy (n = 8) or bisphosphonates (n = 13). CONCLUSION: Sixty percent of patients with severe uveitis had a systemic disease. CS were the most deleterious drugs in spite of bi- or tri-therapy with CS sparing immunosuppressive drugs.

Unusual localisation of chronic arthropathy in lumbar facet joints after parvovirus B19 infection.

Human parvovirus B19 infection may be responsible for acute and chronic arthropathy. We present the case of a woman, who developed a severe chronic parvovirus B19 infection with persistence of DNA parvovirus B19, which was detected in the serum by polymerase chain reaction (PCR). After intravenous immunoglobulin administration she noted a disappearance of the general symptoms and the virus became undetectable by PCR in the serum. However, 1 month later back pain appeared. Magnetic resonance imaging showed bilateral effusions of the apophyseal joints of the lumbar spine (L4-L5). Spine involvement is rarely described during acute or chronic parvovirus B19 infection. In this case it was not possible to determine whether the facet joint arthropathy was reactive or due to persistent articular infection, or induced by immunoglobulin therapy.

Diagnostic specificities and sensitivities of anti dsDNA, anti membrane DNA and anti nucleosomes autoantibodies.

The aim of this study is to evaluate, from 369 routine sera of SLE and control patients, the worth of anti double stranded nuclear DNA, anti nucleosomes autoantibodies and anti membrane DNA for the diagnosis of SLE. Cell membrane associated DNA (mDNA) has been described on B lymphocytes and monocytes, but not on T cells. Antibodies to mDNA were identified by an indirect immunofluorescence assay using a B cell line fixed but not permeabilised. At a 1:40 serum dilution, anti mDNA is almost associated with the diagnosis of systemic lupus erythematosus (SLE). Anti mDNA were shown to be different in specificity as compared with anti double stranded nuclear DNA. We compare its characteristics as diagnostic procedure to the conventional anti dsDNA antibody detection and to the recently introduced anti nucleosome antibody test documented as associated with SLE. It appears that the best sensitivity (0.65) and specificity (0.98) is given by the anti mDNA test.