Israel Medical Association Journal

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: Diseases causing increased pulmonary pressure will subsequently cause a dilation of the pulmonary arteries and right heart chambers.

Objectives: To assess the capability of computed tomography angiography and high resolution CT to diagnose and estimate the severity of pulmonary arterial hypertension as compared with standard means of right heart catheterization, echocardiography and pulmonary function tests.

Methods: The study included 38 patients with PHT[1] who underwent CT angiography and HRCT[2] as part of their routine evaluation. Diagnose included: primary PHT (n=20), Eisenmenger syndrome (n=6), scleroderma (n=3), thromboembolic disease (n=3), and others (n=6). Mean pulmonary artery pressure was 58 mmHg (range 39–92 mmHg) by catheterization and peak systolic pressure 79 mmHg (range 40–135) by echocardiography. Findings for the diameters of the main pulmonary artery and its main branches, the ascending aorta, the right atria and ventricle as well as the position of the interventricular septum were compared with 22 chest CT scans as compared to patients with no known clinical history of pulmonary hypertension, performed for other reasons (trauma, oncology follow-up) during the study period. Correlations were also calculated with recent right heart catheterization, echocardiography and pulmonary function tests of the study group.

Results: Mean main pulmonary artery diameter in the study group was 3.55 ± 0.66 cm, pulmonary artery/ascending aorta ratio 1.2 ± 0.29, right pulmonary artery 2.63 ± 0.49 cm, left pulmonary artery 2.57 ± 0.5 cm. All diameters were significantly different from the control group (P < 0.0001). Main and right pulmonary artery diameters correlated to the pressure measurement by echocardiography (P = 0.001). Bronchial collaterals were found in 11 patients (30%). The position of the interventricular septum correlated well with the echocardiography study.

Conclusions: The size of the main pulmonary artery on CT angiography has a good predictive value regarding the severity of PHT.

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: Syncope is a common clinical problem that often remains undiagnosed despite extensive and expensive diagnostic evaluation.

Objectives: To assess the diagnostic evaluation, costs and prognosis of patients hospitalized for syncope in a tertiary referral center according to discharge diagnosis.

Methods: We retrospectively reviewed the medical records of patients with a diagnosis of syncope discharged from a tertiary referral center in 1999. In addition, mortality data were obtained retrospectively a year after discharge for each patient.

Results: The study group comprised 376 patients. Discharge etiologies were as follows: vasovagal 26.6%, cardiac 17.3%, neurological 4.3%, metabolic 0.5%, unexplained 47.3%, and other 4%. A total of 345 patients were admitted to the internal medicine department, 28 to the intensive cardiac care unit, and 3 to the neurology department. Cardiac and neurological tests were performed more often than other tests, with a higher yield in patients with cardiac and neurological etiologies respectively. The mean evaluation cost was 11,210 ± 8133 shekels, and was higher in the ICCU[1] than in internal medicine wards (19,210 ± 11,855 vs. 10,443 ± 7314 shekels, respectively; P = 0.0015). Mean in-hospital stay was 4.9 ± 4.2 days, which was longer in the ICCU than in medicine wards (7.2 ± 5.6 vs. 4.6 ± 3.5 days, respectively; P = 0.024). Short-term mortality rates (30 days after discharge) and long-term mortality rates (1 year after discharge) were 1.9% and 8.8% respectively, and differed according to discharge etiology. LTM[2] rates were significantly higher in patients discharged with cardiac, neurological and unknown etiologies (not for vasovagal), compared with the general population of Israel (1 year mortality rate for the age-adjusted [65 years] general population = 2.2%). The LTM rate was higher in patients discharged with a cardiac etiology than in those with a non-cardiac etiology (15.4% vs. 7.4%, P = 0.04). Higher short and long-term mortality rates were associated with higher evaluation costs.

Conclusions: Hospitalization in a tertiary referral center for syncope is associated with increased mortality for most etiologies (except vasovagal), cardiac more than non-cardiac. Despite high costs of inpatient evaluation, associated with more diagnostic tests, longer in-hospital stay and higher mortality rates, nearly half of the patients were discharged undiagnosed. Outpatient evaluation should be considered when medically possible.

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

Background: In the course of occurrence of cerebral infarction, cerebral hemorrhage and subarachnoidal hemorrhage episodes, periodicities resembling those found in the solar and geomagnetic activity were found by Kováč and Mikulecký (2005).

Objectives: To investigate putative relationships between two indices of solar activity and one index of geomagnetic activity on one side and the occurrence of cerebral infarction on the other.

Methods: In addition to the 192 monthly cases out of 6100 new cases of cerebral infarction that occurred between January 1989 and December 2004, monthly averages for Wolf numbers, solar flares index and Ap index were included in the analysis. The cross-correlation between each cosmo-geophysical variable on the one hand and the number of new cases of the disease on the other was computed. The quadratic regression with the chosen time delay was also studied using, separately, the Wolf numbers, solar flares and Ap index as the explanatory variable and the number of cases of cerebral infarction as the responding variable.

Results: Significantly negative correlation coefficients between the monthly means of the Wolf numbers, of solar flares and of Ap index on the one hand and monthly numbers of new cases of the disease on the other were found for the delays between -6 and +17 months. The cross-regression results for the delay of +5 months (infarction delayed after each cosmo-geophysical variable by 5 months) displayed a linear decrease except for the Wolf numbers where the parabolic decrease of cases was significant.

Conclusions: An increased intensity of the studied cosmo-geophysical parameters appears to be significantly connected with decreased occurrence of cerebral infarctions, and vice versa. This effect seems to last up to 17 months. The results are supported by a few similar findings in the literature. Putative cosmo-biomedical connections warrant further study to verify them in larger samples and longer time scales. If confirmed, their mechanisms should be elucidated.
 

Background: The frequency of performing percutaneous endoscopic gastrostomy in demented older people has increased in recent years. Several reports indicate flaws in the criteria for performing PEG[1] and in the decision-making process, raising concerns about the adequacy of the consent.

Objectives: To examine knowledge and attitudes of referring doctors and gastroenterologists, and to evaluate attitudes and feelings of family members concerning PEG insertion.

Methods: We conducted a survey of 72 doctors who referred 126 demented patients for PEG, as well as 126 family members and 34 gastroenterologists. Closed-ended questionnaires were designed for each study group, completed by the participants, and computer analyzed.

Results: Approximately 50% of family members expressed dissatisfaction with the decision-making process. Referring physicians reported that PEG insertion was often dictated by the need to transfer patients to a nursing home, with 50% admitting institutional pressure. Most of the referring physicians believed that PEG improved quality of life and longevity, whereas gastroenterologists did not expect an improved quality of life and thought that administrative demands should not intervene in the decision to insert PEG.

Conclusions: The decision-making process in the patient's families regarding PEG insertion for their demented relative is unsatisfactory, often takes place under pressure, and does not provide sufficient information about the procedure or its complications. Interpersonal communication between the patient's family and the medical team need to be improved and institutional demands should not play a major role in the medical decision to insert PEG. Gastroenterologists should take a more active role in the deliberations regarding PEG.