Israel Medical Association Journal

Background: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.
 

Background: Recently, cognitive assessments of patients with Fabry disease highlighted neurocognitive impairment using test batteries that are time and labor intensive.

Objectives: To introduce a user-friendly self-administered tool for cognitive testing in patients with Fabry disease.

Methods: We used a computerized system requiring about 1 hour for patient follow-up. All patients with enzymatic and/or molecular diagnosis of Fabry disease seen in our clinic underwent assessment with the Fabry-specific Mainz Severity Score Index (MSSI) with subscores (neurological, renal, cardiac, and general) and a Mindstreams neurocognitive battery for mild impairment, evaluating memory, executive function, attention, information processing, visual spatial processing, verbal function, and motor skills. A Global Cognitive Score (GCS) was also computed.

Results: Ten patients (3 males, 7 females) were tested (mean age 41.5, range 25–56 years). Males were younger, had moderate nephropathy and no cerebrovascular accident (CVA); their Mindstreams GCS was 85.6–107 points. Three females had mild-moderate (8,10,15 points) neurological MSSI subscores (two CVA); all females had Mindstreams GCS of 59–107.7 points. Below-average performance was prevalent, particularly in information processing and motor skills consistent with mild impairment. Average GCS in females (90.3 points) was lower than in males (98.2 points). For individual patients, performance was poorest in information processing (n=4), attention (n=2), motor skills (n=2), verbal function (n=1), and visual spatial processing (n=1).

Conclusions: MindStreams may simplify cognitive assessment monitoring in Fabry disease.
 

Background: Since clinical signs of meningeal irritation in infants may be absent or misleading, the American Academy of Pediatrics in 1996 recommended that a lumbar puncture be performed in young children following a febrile seizure. Recent evidence supports a conservative approach in children who do not look ill at the time of the physician's assessment. Moreover, seizures as the presenting or sole symptom of bacterial meningitis are very rare.

Objectives: To assess physicians’ compliance with the Academy’s recommendations and to determine the incidence of meningitis among febrile seizure patients, including those who did not undergo the puncture.

Methods: We conducted a retrospective analysis of the number of punctures obtained in febrile seizure patients aged 6–24 months, focusing on the clinician's indications for performing the procedure and on the clinical course of children who did not undergo the puncture.

Results: Among 278 patients (84% simple febrile seizure), 52 (18.7%) underwent the procedure. It was performed in 38% of 45 complex febrile seizure cases and in 48% of 91 infants younger than 12 months of age. Aseptic meningitis occurred in two infants, both with post-ictal apathy. Bacterial meningitis was not found and in none of the patients who did not undergo the puncture was meningitis later diagnosed.

Conclusions: Compliance with the Academy’s recommendations was low, as emergency room physicians based their decision whether to obtain a lumbar puncture solely on clinical grounds. No case of bacterial meningitis was detected among 278 young children with a febrile seizure, including those who did not undergo the puncture.
 

Background: Fatigue is a common complaint in primary care and has a broad differential diagnosis, making the approach complex and often ineffective.

Objectives: To follow the course of adults without a significant known background disease who complain of fatigue for the first time, and to characterize the family physician’s approach.

Methods: The study population comprised a random sample of 299 patients aged 18–45 who presented with fatigue as a first-time single complaint to their family physician. Excluded were patients with chronic diseases or states that may include signs of fatigue. We analyzed the index encounter data, the diagnostic and laboratory tests, the medications prescribed and the one year clinical outcome.

Results: Seventy percent were women, average age 30.5 years, and 69% had no known co-morbidities; 57% of the patients were physically examined at the first visit and most (78.6%) were sent for laboratory analysis. Five percent of laboratory tests were positive. Eighty patients (26.8%) were given a specific diagnosis, with the leading diagnoses being anemia and infectious diseases; 18.7% were given sick leave at the first visit. Fatigue was more common in early summer.

Conclusions: The majority of young healthy patients complaining of fatigue are not diagnosed with an organic physiological disorder. Many of the study patients were sent for laboratory tests but in most cases these tests were not contributory to the diagnosis or management. It seems likely that the most efficient strategy would be watchful follow-up with a minimum of testing.

Background: Patient protection requires the provision of informed consent for participation in medical research. The MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) is frequently used for screening the capacity of research subjects to consent to participate in research.

Objectives: To evaluate the utility of the Hebrew translation of the MacCAT-CR for the assessment of capacity of patients with chronic schizophrenia to provide informed consent to participate in clinical trials.

Methods: We evaluated the translated MacCAT-CR by comparing the capacity of patients with chronic schizophrenia to provide informed consent to participate in clinical trials. The following standardized neurocognitive assessment tools were used: Addenbrooke’s Cognitive Examination (ACE) and Frontal Assessment Battery (FAB), as well as the attending doctor’s assessment.

Results: Twenty-one patients participated. Mean MacCAT-CR score was12 ¡À 10.57 (range 0¨C32), mean FAB score was 9.9 ¡À 4.77 (range 1¨C18), mean ACE was 59.14 ¡À 16.6 (range 27¨C86) and mean doctor’s assessment was 5.24 ¡À 1.18 (range 3¨C7).

Conclusions: The Hebrew-version of the MacCAT-CR helped identify patients with the capacity to provide informed consent for participation in research. Patients with FAB scores ¡Ý 12 tended to score higher on the Hebrew-version of the MacCAT-CR, thus confirming the utility of the Hebrew version of the MacCAT-CR. During the screening process for clinical trials it may be practical to administer the concise FAB questionnaire, and then administer the MacCAT-CR only to those who scored ¡Ý 12 on the FAB.

Current treatments for systemic lupus erythematosus (SLE) are effective in reducing morbidity and mortality but are not specific and have severe adverse effects. Based on understanding of the different dysregulated immunological pathways involved in SLE pathogenesis, specific targeted therapies were developed. This review presents the current and the near-future novel biological immune targeted treatments, such as B cell-targeted therapy, cytokine blockade, peptide-based treatments and other novel treatments for SLE.