Israel Medical Association Journal

Background: Polymorphonuclear leukocyte priming and low grade inflammation are related to severity of kidney disease. Erythropoietin-receptor is present on PMNLs[1].

Objectives: To evaluate the effect of 20 weeks of EPO[2]-alpha treatment on PMNL characteristics in relation to the rate of kidney function deterioration in patients with chronic kidney disease.

Methods: Forty anemic chronic kidney disease patients, stage 4-5, were assigned to EPO and non-EPO treatment for 20 weeks. A group of 20 healthy controls was also studied. PMNL priming and PMNL-derived low grade inflammation were estimated, in vivo and ex vivo, before and after EPO treatment: The rate of superoxide release, white blood cells and PMNL counts, serum alkaline phosphatase and PMNL viability were measured. EPO-receptor on PMNLs was assayed by flow cytometry. The effect of 20 weeks of EPO treatment on kidney function was related to the estimated glomerular filtration rate.

Results: EPO treatment attenuated superoxide release ex vivo and in vivo and promoted PMNL survival ex vivo. Decreased low grade inflammation was reflected by reduced WBC[3] and PMNL counts and ALP[4] activity following treatment. EPO retarded the deterioration in GFR[5]. The percent of PMNLs expressing EPO-R[6] was higher before EPO treatment and correlated positively with the rate of superoxide release. After 20 weeks of EPO treatment the percent of PMNLs expressing EPO-R was down-regulated.

Conclusions: These non-erythropoietic properties of EPO are mediated by EPO-R on PMNLs, not related to the anemia correction. A new renal protection effect of EPO via attenuation of PMNL priming that decreases systemic low grade inflammation and oxidative stress is suggested.

Background: Based on the outcome of several randomized controlled trials, the orally active leukotriene receptor antagonist montelukast (Singulair®, Merck) has been licensed for treatment of asthma. The drug is favored for treating childhood asthma, where a therapeutic challenge has arisen due to poor compliance with inhalation therapy.

Objectives: To assess the efficiency of and satisfaction with Singulair® in asthmatic children under real-life conditions.

Methods: Montelukast was prescribed for 6 weeks to a cohort of 506 children aged 2 to 18 years with mild to moderate persistent asthma, who were enrolled by 200 primary care pediatricians countrywide. Four clinical correlates of childhood asthma – wheeze, cough, difficulty in breathing, night awakening – were evaluated from patients' diary cards.

Results: Due to under-treatment by their physicians, almost 60% of the children were not receiving controller therapy at baseline. By the end of the study, which consisted of montelukast treatment, a significant improvement over baseline was noted in asthma symptoms and severity, as well as in treatment compliance. The participating pediatricians and parents were highly satisfied with the treatment.

Conclusions: The results of this extensive study show that the use of montelukast as monotherapy in children presenting with persistent asthma resulted in a highly satisfactory outcome for themselves, their parents and their physicians.
 

Background: Acupuncture and public interest in this modality have increased over recent years in Israel and throughout the western world.

Objectives: To compare the knowledge and attitudes of physicians to medical students with regard to acupuncture.

Methods: An anonymous questionnaire was completed by internists and medical students at the Soroka Medical Center.

Results: There were 122 respondents in all, 57 of them women (46.7%). The study sample included 40 physicians (33%), 39 fifth year medical students (32%) and 43 second year medical students (35%). The majority of participants (93.4%) had never received training in acupuncture and 84.4% had never undergone acupuncture therapy themselves. In these variables there were no significant differences between the physicians and the students. The participants’ level of knowledge of acupuncture was very low, with 40% unable to answer even one question (of eight) correctly. Despite the poor level of knowledge and the lack of personal exposure to acupuncture, 90 participants (74%) believed that acupuncture has more than a placebo effect, and 57 (42%) believed it was important to include acupuncture in medical education. There were no statistically significant differences in the attitudes of physicians and medical students to acupuncture.

Conclusions: The level of knowledge and exposure of physicians and medical students to acupuncture is low. However, both groups have relatively positive attitudes to this modality as an acceptable treatment for health problems and were open to its inclusion in the medical school curriculum.

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.

Background: Falls are a common problem among hospitalized patients, having a significant impact on quality of life and resource utilization.

Objectives: To develop and validate a fall-risk assessment tool for patients hospitalized in the department of medicine that will combine simplicity with adequate accuracy for routine use.

Methods: This observational cohort study was conducted on the medical wards of an urban tertiary teaching hospital, and included all patients who fell in the medical wards during a 1 year period (n=140) compared to other hospitalized patients.

Results: Significant correlates of falls were previous falls, impairing medical conditions, impaired mobility, and altered mental state. In multivariate logistic regression analyses, only previous falls (odds ratio 3.8 with 95% confidence interval 2.65–5.45, P < 0.0001) and acute impairing medical conditions (OR[1] 1.56, CI[2] 1.06–2.29, P < 0.05) correlated independently with a higher risk for falls. Impaired mobility retained an OR of 1.46 (CI 0.95–2.24, P = 0.084). Accordingly, defining patients with either a history of previous falls or both acute impairing medical state and impaired mobility as fall-prone patients provided a sensitivity and specificity of 67% and 63%, respectively. In a subsequent prospective validation trial on 88 patients who fell during hospitalization and 436 controls, the sensitivity and specificity of this fall-risk grouping were 64% and 68% respectively.

Conclusions: Our new simple and easy-to-use fall-risk assessment tool identified most of the fall-prone patients. These findings suggest that using this tool may enable us to prevent two-thirds of falls on the medical ward by providing effective fall-prevention facilities to only one-third of the patients.

Background: Non-operative management following abdominal stab wounds is possible in selected patients who are both hemodynamically stable and do not have signs of peritonitis. However, the rate of failure of non-operative management is higher in Israel than in western countries.

Objectives: To assess the patterns of injury following abdominal stabbing.

Methods: Data from the Israeli Trauma Registry were used to identify all patients with abdominal stab injury admitted to eight different trauma centers between 1997 and 2004.

Results: The number of patients admitted per year more than doubled between 1997 and 2004, from 257 to 599. The percentage of patients with severe injury (Index Severity Score ≥ 16) increased from 9.4% to 19.0%. The incidence of multiple stab injuries almost doubled, from 37% to 62%.

Conclusions: Review of the data in the Israeli Trauma Registry indicates an increase in both absolute rate and relative incidence of serious stab injuries. This indicates that patterns of injury following stab wounds are not necessarily similar, not even within the same geographical area over time.
 

There has been a paradigm shift in the treatment of rheumatoid arthritis in recent years. Early and aggressive treatment with good control of disease activity has improved the prognosis of the disease, however, there is significant variability in the response of patients to different therapeutic agents. Hence it is essential to find the predictors of response to a drug at baseline so that we can avoid the delay in achieving remission and improve the outcome. Here we review the literature on available predictors for treatment response in general and specifically for methotrexate and biological agents. We also look at specific scores or indices that can help predict the response in individual patients.

Background: The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA[1]. In addition, these alleles may also have relevance for disease outcome. Anti-CCP[2] antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information available regarding any relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.

Objectives: To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.

Methods: Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.

Results: Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF[3] positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 5.828, P < 0.01). There was no correlation between RF positivity and serum levels, CRP[4] serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with shared epitope positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (P < 0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE[5]-negative patients (76.8 ± 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (P < 0.01).

Conclusions: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus, patients carrying HLA-DRB1*04 alleles exhibited an overall tenfold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations