Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of the innate and adaptive immune systems with the production of autoantibodies by stimulated B lymphocytes. The BLyS protein (B lymphocyte stimulator) is secreted mainly by monocytes and activated T cells and is responsible for the proliferation, maturation and survival of B cells.

Objectivs: To study sera BLyS level and its clinical significance in Israeli lupus patients over time.

Methods: The study population included 41 lupus patients (8 males, 33 females; mean age 35.56 ± 15.35 years) and 50 healthy controls. The patients were followed for 5.02 ± 1.95 years. We tested 221 lupus sera (mean 5.4 samples/patient) and 50 normal sera for BLyS levels by a capture ELISA. Disease activity was determined by the SLEDAI score.

Results: Sera BLyS levels were significantly higher in SLE patients than in controls (3.37 ± 3.73 vs. 0.32 ± 0.96 ng/ml, P < 0.05). BLyS levels were high in at least one sera sample in 80.5% of the patients but were normal in all sera in the control group. There was no correlation between sera BLyS and anti-ds-DNA autoantibody levels. BLyS levels fluctuated over time in sera of lupus patients with no significant correlation to disease activity.

Conclusions: Most of our lupus patients had high sera BLyS levels, suggesting a role for BLyS in the pathogenesis and course of SLE. Our results support the current novel approach of targeting BLyS (neutralization by antibodies or soluble receptors) in the treatment of active lupus patients.

Background: The role of routine active surveillance cultures (ASCs) in predicting consequent blood stream infections is unclear.

Objectives: To determine prospectively whether routine screening ASCs obtained on admission to the intensive care unit (ICU) can predict the causative agent of subsequent bloodstream infections.

Methods: We prospectively studied a cohort of 100 mechanically ventilated patients admitted consecutively to a 16-bed ICU. On admission, ASCs were obtained from four sites: skin cultures (swabs) from the axillary region, rectal swabs, nasal swabs, and deep tracheal aspirates. Thereafter, cultures were obtained from all four sites daily for the next 5 days of the ICU stay.

Results: Of the 100 recruited patients 31 (31%) had culture-proven bacteremia; the median time to development of bacteremia was 5 days (range 1–18). Patients with bacteremia had a longer median ICU stay than patients without bacteremia: 14 days (range 2–45) vs. 5 days (1–41) (P < 0.001). ICU and 28 day mortality were similar in patients with and without bacteremia. Most ASCs grew multiple organisms. However, there was no association between pathogens growing on ASCs and eventual development of bacteremia.

Conclusions: ASCs obtained on ICU admission did not identify the causative agents of most subsequent bacteremia events. Therefore, bloodstream infections could not be related to ASCs.

High mobility group box 1 is a nuclear protein participating in chromatin architecture and transcriptional regulation. When released from cells, HMGB1[1] can also act as a pro-inflammatory mediator or alarmin. Upon stimulation with lipopolysaccharides or tumor necrosis factor-alpha, HMGB1 is secreted from certain cells such as monocytes/macrophages and fosters inflammatory responses. In addition, HMGB1 is passively released from necrotic cells and mediates inflammation and immune activation. In contrast, during apoptotic cell death, nuclear HMGB1 gets tightly attached to hypo-acetylated chromatin and is not released into the extracellular milieu, thereby preventing an inflammatory response. There is accumulating evidence that extracellular HMGB1 contributes to the pathogenesis of many inflammatory diseases, including autoimmune diseases. Increased concentrations of HMGB1 have been detected in the synovial fluid of patients with rheumatoid arthritis. In animal models of RA[2], HMGB1 appears to be crucially involved in the pathogenesis of arthritis, since neutralization of HMGB1 significantly ameliorates the disease. Also, in the serum and plasma of patients with systemic lupus erythematosus we detected substantial amounts of HMGB1, which may contribute to the disease process. However, investigations of blood concentrations of HMGB1 and its relevance in human diseases are hindered by the lack of reliable routine test systems.

Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by disabling fatigue, difficulty in concentration and memory, and concomitant skeletal and muscular pain. Several mechanisms have been suggested to play a role in CFS[1], such as excessive oxidative stress following exertion, immune imbalance characterized by decreased natural killer cell and macrophage activity, immunoglobulin G subclass deficiencies (IgG-1[2], IgG-3) and decreased serum concentrations of complement component. Autoantibodies were also suggested as a possible factor in the pathogenesis of CFS. Recent studies indicate that anti-serotonin, anti-microtubule-associated protein 2 and anti-muscarinic cholinergic receptor 1 may play a role in the pathogenesis of CFS. It has been demonstrated that impairment in vasoactive neuropeptide metabolism may explain the CFS symptoms

Background: In an era of increasing antimicrobial resistance, knowledge of local antimicrobial susceptibility patterns of common uropathogens is essential for prudent empiric therapy of community-acquired urinary tract infections.

Objectives: To define antimicrobial susceptibility of Gram-negative uropathogens in northern Israel over a 10 year period and to compare it with antibiotic-use patterns in the same community.

Methods: We tested the susceptibility of all Gram-negative urinary isolates from outpatients at HaEmek Medical Center over the years 1995, 1999, 2002 and 2005 to common antimicrobial agents. MIC₉₀ of Escherichia coli to some of these agents was determined and antibiotic consumption data over the years 2000–2005 (DDD/1000/day) were obtained.

Results: We observed a rise in susceptibility rates of E. coli to amoxicillin-clavulanate, trimethoprim-sulfamethoxazole and nitrofurantoin and of other Gram-negative isolates to amoxicillin-clavulanate, ceftriaxone and cephalothin. Susceptibility rates of all Gram-negative uropathogens to ciprofloxacin decreased significantly. MIC₉₀ of E. coli for all drugs tested remained stable. There was a significant decrease in the use nitrofurantoin and TMP-SMX[1] and a significant increase in the use of ampicillin, cephalothin and ceftriaxone.

Conclusions: Antibiotic resistance patterns mostly remained unchanged or improved slightly. There was, however, a constant decrease in susceptibility of all Gram-negative uropathogens to ciprofloxacin. Antibiotic use patterns could not explain the changes seen in antibiotic susceptibility patterns.

Background: Seasickness is thought to result from conflicting inputs from the vestibular, visual and somatosensory systems. The otolithic organs, which are responsible for the sensation of linear acceleration and tilt, are important in the pathogenesis of seasickness. Vestibular evoked myogenic potentials test is an objective evaluation of saccular function.

Objective: To examine whether saccular function is related to the pathogenesis of seasickness.

Methods: VEMP1 was performed in 10 subjects susceptible to seasickness and in 14 non-susceptible subjects.

Results: Bilateral VEMP responses were obtained in 7 (50%) of the non-susceptible subjects and 1 (10%) of the susceptible subjects. No differences were found between the groups in P13 and N23 wave latencies, amplitudes, N13-P23 inter-peak latencies, and peak-to-peak asymmetry ratios. More subjects in the susceptible group had asymmetry ratios > 35%.   

Conclusions: The attenuated saccular response might be explained in the context of the neural-mismatch theory and/or the subjective vertical theory, as reflecting an adaptation effort to sea conditions. A larger study is necessary to determine whether a statistically significant difference in VEMP responses exists between seasickness-susceptible and non-susceptible subjects.
 

Diabetic retinopathy is one of the leading causes of blindness worldwide.

Objectives: To determine the prevalence of different pathogens in patients presenting to our sexually transmitted disease clinic with hematospermia.

Methods: Between January 1999 and January 2000, 16 patients presented to our STD[1] clinic with hematospermia after other non-infectious pathologies had been excluded by a referring physician. After obtaining informed consent, subjects completed a questionnaire addressing symptoms and sexual behavior. First void urine samples, as well as genitourinary and serum specimens were tested for Chlamydia trachomatis, Ureaplasma urealyticum and Herpes simplex virus. Standard bacterial cultures were also performed.

Results: Laboratory testing detected a pathogen in 12 of the 16 males presenting with hematospermia. The sexually transmitted pathogens detected were Herpes simplex virus in 5 patients (42%), Chlamydia trachomatis in 4 (33%), Enterococcus fecalis in 2 (17%), and Ureaplasma urealyticum in 1 (8%). In all cases in which a pathogen was identified, the appropriate antimicrobial agent was administered. Symptoms resolved for each patient following antimicrobial therapy. During a 1 year follow-up, all 12 patients remained free of disease.

Conclusions: Recent advances in microbiologic diagnostic techniques have facilitated the detection of pathogens in patients with hematospermia, thereby enhancing the efficacy of treatment.

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[1] STD = sexually transmitted disease