Israel Medical Association Journal

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: 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.

Background: Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus.

Objectives: To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM[1] in a transfer model of NOD mice.

Methods: Our vaccination technique involved the insertion of CD44s[2] or CD44v[3] cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN[4] were implanted 20 days before and 3 days after cell transfer.

Results: In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed.

Conclusions: These findings may open new opportunities for IDDM therapy in the future.

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.

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