Israel Medical Association Journal

Background: Multiple sclerosis (MS) is a common demyelinating disorder of the central nervous system (CNS) and although it is a well-established autoimmune disease its ethiopathogenesis has yet to be fully elucidated. The disease may present in several clinical forms that are closely associated with disease morbidity. In recent years various environmental and hormonal factors have been implicated in the pathogenesis of autoimmunity.

Objectives: To evaluate ferritin and prolactin levels in MS patients and their correlation with clinical manifestations of the disease.

Methods: Serum samples from 150 multiple sclerosis patients were evaluated for demographic characteristics, clinical parameters as well as prolactin and ferritin levels utilizing the Liaison chemiluminescent immunoassays (DiaSorin, Italy). Sera from 100 matched healthy donors were used as controls.

Results: Hyperprolactinemia was documented in 10 of 150 MS patients (6.7%) and hyperferritinemia in 12 (8%), both of which were significantly more common in this group compared with healthy controls (P ≤ 0.01 and P = 0.02 respectively). Among female MS patients, elevated prolactin levels were related to the secondary progressive type of disease (P = 0.05), whereas hyperferritinemia was associated with male gender (P = 0.03) and with the relapsing progressive type of the disease (P = 0.02). An inverse association was found between hyperferritinemia and the relapsing-remitting type of MS in male patients (P = 0.05)

Conclusions: Our results suggest a plausible association between these biomarkers and certain clinical types and gender among MS patients. Further studies combining clinical data, CNS imaging and these markers are warranted.
 

Background: There are several treatment options for simple bone cysts, with treatment depending mainly on the experience and preference of the surgeon and the extension and location of the cyst.

Objectives: To assess our experience with the surgical treatment of bone cyst lesions in pediatric patients at one institution by the same group of surgeons.

Methods: The study group comprised 60 patients (43 boys, 17 girls) treated surgically for monostatic lesions between January 2002 and July 2007. The mean age at surgery was 11.8 years (range 4–17 years). Mean follow-up was 4.2 years. Most of the lesions were located at the proximal humerus. Patients were divided into five groups according to treatment method: a) corticosteroids (methylprednisolone 40-80 mg) (n=26); b) curettage and bone grafting (fibula or iliac crest) (n=16); c) aspiration of the bone cavity and subsequent bone marrow transplantation (n=10); d) internal preventive fixation using an elastic stable intramedullary nail (n=5); and e) curettage and implantation of a synthetic cancellous bone substitute (pure beta-tricalcium phosphate substitute, ChronOS®, Synthes, Switzerland) (n=3).

Results: Treatment success was evaluated by the Capanna criteria. Successful results were observed in 68% (18 complete healing, 23 healing with residual radiolucent areas), 30% recurrence rate, and no response to treatment in one patient (2%). We recorded recurrence in 50% of the children treated by corticosteroid injection, and one child did not respond to treatment.

Conclusions: The best results were achieved in children treated by curettage and the subsequent use of an osteoconductive material, and in children treated with elastic intramedullary nail fixation. Despite our limited experience with calcium-triphosphate bone substitute, the treatment was mostly successful. Because of the short follow-up, further observation and evaluation are necessary.

Asthma is an airway disease, yet that airway extends all the way to the alveolar tissue area. Pathohistiological as well as physiological and clinical studies have recently documented this aspect of asthma. The implications of this are important for all asthmatic patients, but particularly for those whose asthma is more difficult to control. Many of the inhaled preparations used as therapy for asthma are of relatively large particle size. 

Thus, the deposition of these medications is mainly in the central and medium sized airways and very little of a given actuation gets to the distal airways. Ultrafine inhaled steroid particles have been shown to reach the more peripheral portions of the airway, and improvement in outcome variables such as air trapping as well as symptomatic outcomes have been demonstrated. This review focuses on anatomic airway changes, physiological changes of the distal airways, clinical outcome data, and particle size of inhaled preparations.

Mesenchymal stromal cells are multipotent cells capable of tissue repair and immune modulation. They are primarily found in bone marrow, but are also present in other tissues of mesenchymal origin, such as fatty tissue, muscle, tendons, etc. MSC[1] can easily be obtained by bone marrow aspiration, showing a rapid expansion in vitro. New protocols enable cell culture without the use of animal-derived sera and artificial growth factors. Avascular necroses of the bone may have different causes. AVN[2] in autoimmune and hematological diseases show a strong association with corticosteroid treatment, which is often unavoidable in severe cases. Until recently, core decompression of the affected osseous area was the standard approach. Because of their differentiation properties, easy accessibility and proliferative capacity, autologous MSCs could potentially complement AVN treatment by adding fresh “osteogenic cells” to the healing process.

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.

The antiphospholipid syndrome is characterized by recurrent fetal loss, venous and/or arterial thrombosis, and thrombocytopenia associated with elevated titers of lupus anticoagulant and anticardiolipin antibodies. Although thrombosis is the characteristic vascular involvement in APS[1], the development of vascular aneurysms in patients with APS has been reported. We describe four patients with established APS, who developed abdominal aortic aneurysm, and review the literature on previous published cases of arterial aneurysms developing in patients with APS. In addition, we discuss the possible pathophysiological association between APS and the development of this vascular abnormality.

Background: Ethnicity has been associated with variance in warfarin treatment regimens in various settings.

Objectives: To determine whether ethnicity is associated with variance in patient management in Israel.

Methods: Data were extracted from the electronic patient records of Clalit Health Services clinics in the Sharon Shomron region. The study group comprised all patients treated with warfarin who performed international normalized ratio tests for at least 6 months in 2003. The proportion of tests of each patient within the target range was calculated, as was the crude average rates and 95% confidence intervals for Jewish and Arab patients. The data were then stratified by patient's gender, specialty of attending physician, patient's age, and the country where the physician studied medicine.

Results: We identified 2749 Jews and 293 Arabs who met the inclusion criteria of the study. The crude average rate of patients’ INR[1] tests within the target range was 62.3% among Jews (95% CI[2] 61.5–63.1) and 52.7% (95% CI 49.9–55.5) among Arabs. When stratified by gender, age, and the treating physician's specialty and country of education, the stratum-specific rates among Jewish patients were consistently higher than among Arabs.

Conclusions: These results suggest that cultural differences regarding adherence to recommendations for drug therapy in addition to genetic factors may be associated with this variance.