Israel Medical Association Journal

Background: Uveal melanoma is the most common primary intraocular tumor in adults. In the last two decades the Hadassah-Hebrew University ocular oncology clinic has become a referral center for uveal melanoma patients.

Objectives: To describe the characteristics of uveal melanoma patients in Israel, their treatment modalities and outcomes during the years 1988–2007.

Methods: Data were collected from the files of uveal melanoma patients in the departments of ophthalmology and oncology in our facility. Statistical analysis was performed using JMP statistical software.

Results: Data were available for 558 patients. The annual incidence of uveal melanoma in the last 5 years was 47.2 ± 7.1 new cases per year (mean ± standard error). There were 309 women (55.4%). The age at diagnosis was 60.8 ± 16.5 years (range 5–95). Overall, 6.6%, 16.8% and 86.9% involved the iris, ciliary-body and choroid, respectively. Tumors were classified as small, medium and large (9.0%, 64.5% and 17.9%, respectively) according to the COMS grouping criteria. The most common primary treatment was brachytherapy (74%), followed by enucleation (17.9%). Local recurrence was noted in 11.1% of patients, while metastases developed in 13.3%. The 5, 10 and 15 year melanoma-related mortality rate was 11.4%, 17.0% and 23.3%, respectively. Of the overall study population 9.3% died of metastatic uveal melanoma.

Conclusions: Uveal melanoma patients in Israel have tumors with characteristics similar to those in other countries. Brachytherapy is the predominant treatment, the local recurrence rate is low, and survival is comparable to that reported in the medical literature.

Background: In both adjuvant arthritis and rheumatoid arthritis edema and inflammation appear in synovial joints. Edema or effusion reflects an imbalance in lymph dynamics. Purified micronized flavonoid fraction is mainly used in the treatment of chronic venous insufficiency. This compound improves lymphatic drainage with a signicant increase in lymphatic flow and lymphatic pulsality. It is suggested that the beneficial effect of purified micronized flavonoid fraction may be involved in the treatment of adjuvant arthritis in rats.

Objectives: To evaluate the effect of Detralex on methotrexate prophylactic treatment of adjuvant arthritis in rats.

Methods: Groups of rats with adjuvant arthritis were treated with methotrexate (0.6 mg/kg/week), Detralex (20 mg/kg/day) and their combination for 50 days from adjuvant application. Hind paw swelling, arthrogram scores, serum albumin level, serum nitrite/nitrate concentrations, whole body mineral density and X-ray scans of synovial joints were evaluated as markers of inflammation and destructive changes associated with arthritis.

Results: Long-term prophylactic treatment with low dose methotrexate significantly inhibited the markers of both inflammation and arthritis. Detralex administered alone slightly decreased both the hind paw swelling and the arthritic score. Other inflammatory and arthritic markers were not significantly influenced. However, detralex combined with methotrexate markedly potentiated the beneficial effects of methotrexate, which resulted in a more significant reduction in hind paw swelling, arthritic scores, and serum concentrations of nitrite/nitrate. Interestingly, the arthritis-induced decrease of BMD[1] in AA[2] rats was significantly lower only in the group treated with the combination of Detralex+methotrexate.

Conclusion: Detralex increased the therapeutic efficacy of methotrexate basal treatment in AA. We suggest that this may be related to the beneficial effect of Detralex on microcirculation, especially on venules and lymphatic vessels.

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 recent years there has been an increase in endovascular repair of thoracic aortic aneurysms. In cases of insufficient neck length, occlusion of left subclavian artery achieves proper sealing and is usually well tolerated. Selected cases require revascularization of the left subclavian artery, including patients after coronary bypass surgery (left internal mammary to left anterior descending) and those with arm claudication or subclavian steal syndrome.

Objectives: To evaluate the tolerability of left subclavian artery occlusion by stent graft without revascularization.

Methods: Thirty patients with thoracic aortic aneurysms underwent endovascular repair between July 2000 and November 2004. Eleven of them had occlusion of the left subclavian artery that required revascularization in two. Follow-up (average 3 years) included a) blood pressure measurements of both arms at rest, after effort and pulse palpation, and b) vertebral blood flow by duplex scan.

Results: Of nine patients with no revascularization, 8 (89%) tolerated left subclavian artery occlusion with no claudication or steal syndrome; one (11%) suffered mild claudication only after effort and required no intervention. No left radial pulses were palpated in the nine patients. Blood pressure measurements in the left arm showed an average decrease of 40%, which remained constant after induced effort in all patients and was clinically insignificant. Duplex scan demonstrated reverse flow in the left vertebral artery in 8 of 9 patients (89%) and occlusion in 1 (originating in the arch and covered by the stent graft) with no clinical symptoms.

Conclusions: Left subclavian artery occlusion by stent graft is a tolerable procedure in the long term. In most cases, the constant decrease in blood pressure remained unchanged during follow-up and had no significant adverse affects. Most patients do not require revascularization prior to the endovascular procedure.