Israel Medical Association Journal

Background: Regular physical activity is known to have a beneficial impact on multiple cardiovascular risk factors, but there is no routine provision of exercise training programs to patients after ischemic stroke.

Objectives: To assess the tolerability, safety and effect of an outpatient supervised exercise training program in patients after a non-disabling ischemic stroke.

Methods: Patients discharged home following a minor ischemic stroke (modified Rankin scale; mRS ≤ 2) were referred to a 3 month outpatient supervised exercise training program, performed twice weekly as prescribed by a physiologist and supervised by physical therapy. Exercise capacity was evaluated by the 6 minute walk test, and by the modified Bruce exercise test.

Results: Of the 52 patients who met the selection criteria, 43 underwent supervised exercise training within 2 months of stroke onset and 9 did not (control group). The baseline characteristics were comparable between the two groups. Following the exercise training program, an improvement in exercise capacity was observed manifested by improvement in the 6 minute walk test (444 ± 90 to 557 ± 99 meters in the exercise group vs. 438 ± 101 to 418 ± 126 in the control group; P = 0.002 for the score changes) and in the exercise duration achieved in the modified Bruce test and the metabolic equivalents achieved [9.6 ± 3.7 to 12.4 ± 3.2 minutes and 6.2 ± 2.8 to 8.5 ± 3.4 respectively in the exercise group (n=41) vs. 9.2 ± 3.5 to 8.0 ± 3.4 min and 5.8 ± 1.8 to 5.8 ± 2.8 in the control group (n=7); P = 0.0009 and 0.01 for score changes, respectively].

Conclusions: An outpatient supervised exercise training program after a minor ischemic stroke is feasible, well tolerated and is associated with improvement in exercise capacity. We strongly recommend that an aerobic exercise program be offered to suitable patients after an ischemic stroke.
 

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.

Background: Carotid artery stenting is used as an alternative to surgical endarterectomy.

Objectives: To determine the outcome of CAS[1] in a retrospective cohort of patients.

Methods: Between July 1999 and March 2003, 56 consecutive patients with carotid artery stenosis who were considered ineligible for surgery were treated (45 male, 11 female, mean age 69). All cases were performed prior to the introduction of distal protective devices in Israel.

Results: Intraprocedural complications included transient neurological findings in 5 patients (8%), cerebrovascular accident in 2 (3%), hemodynamic changes in 11 (18%), and 4 procedural failures. Post-procedural complications included transient ischemic attack in 3 patients and cardiovascular accident in 6 (10%). At 30 days follow-up, three patients (5%) remained with signs of CVA[2]. Two patients (3%) died during the post-procedural period and 16 (28%) during the 5 year follow-up, one due to recurrent CVA and the remainder to non-neurological causes. Five-year carotid Doppler follow-up was performed in 25 patients (45%), which revealed normal stent flow in 21 (84%), 50–60% restenosis in 3 patients (12%) and > 70% restenosis in one patient (4%).

Conclusions: This study confirms that stent procedures are beneficial for symptomatic carotid stenosis in patients not eligible for surgery.

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.

Management of asthma is currently based on symptoms (in children, usually a second-hand report from parents) and lung function measurements. Inhaled steroids, targeted at controlling airway inflammation, are the mainstay of asthma management. Due to possible side effects they should be used at the lowest possible doses while asthma is adequately controlled. Fractional exhaled nitric oxide is a simple non-invasive method to assess inflammation in asthma and its role in asthma management is increasing in popularity. The present review summarizes recent research on the use of FeNO[1] in monitoring airway inflammation and optimizing asthma management. The addition of FeNO measurements to the conventional assessment of asthma control appears promising. The practicability of including this measuring method into everyday clinical practice is currently being evaluated.

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.

Medical screening is not a tangible existent tool in autoimmune disorders as it is in other illnesses. Numerous attempts are made to identify individuals destined to develop an autoimmune disease, including analysis of the genetic background, which along with the immunological profile, may assist in identifying those individuals. If these efforts turn out to be successful they may lead to the possibility of proactive measures that might prevent the emergence of such disorders. This review will summarize the attempts made to pursue autoantibodies specific for the central nervous system as potential predictors of autoimmune neurological disorders.

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