George Vaiopoulos

The Effect of Olive Oil and Fish Consumption on Rheumatoid Arthritis - A Case Control Study

In an interview based, case control study of Rheumatoid Arthritis (RA) 168 cases and 137 controls were included. Patients and controls were interviewed with regard to a variety of socioeconomic, medical and dietary factors. During univariate analysis it was found that RA cases consumed significantly less olive oil and fish and adhered more rarely to the dietary restrictions traditional in Orthodox lent than controls. Applying multiple logistic analysis though (by which several variables were controlled for), only the association with olive oil consumption and lent adherence remained significant. More specifically; an increase in olive oil consumption by two times per week, resulted in a Relative Risk (RR) for development of RA of 0.49, whereas adherence to lent during the 27 weeks per year prescribed by the Orthodox Church, resulted in a RR of 0.33. We conclude that olive oil consumption and adherence to Orthodox lent may have a protective effect on the development and/or the severity of RA. This is a hypothesis generated by the present study that needs verification.

Colour duplex sonography of temporal arteries before decision for biopsy: a prospective study in 55 patients with suspected giant cell arteritis.

Although a temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis (GCA), there is considerable evidence that characteristic signs demonstrated by colour duplex sonography (CDS) of the temporal arteries may be of diagnostic importance. We aimed to test the hypothesis that CDS can replace biopsy in the algorithm for the approach to diagnose GCA. Bilateral CDS was performed in consecutive patients older than 50 years with clinically suspected GCA, as well as in 15 age- and gender-matched control subjects with diabetes mellitus and/or stroke and 15 healthy subjects, to assess flow parameters and the possible presence of a dark halo around the arterial lumen. Unilateral temporal artery biopsy was then performed in patients with suspected GCA, which was directed to a particular arterial segment in case a halo was detected in CDS. Final diagnoses, after completion of a 3-month follow-up in 55 patients, included GCA (n = 22), polymyalgia rheumatica (n = 12), polyarteritis nodosa, Wegeners, and Adamantiades-Behçets diseases (n = 3), and neoplastic (n = 8) and infectious diseases (n = 10). A dark halo of variable size (0.7–2.0 mm) around the vessel lumen was evident at baseline CDS in 21 patients (in 12 and 9 uni- or bilaterally, respectively) but in none of the controls. The presence of unilateral halo alone yielded 82% sensitivity and 91% specificity for GCA, whereas the specificity reached 100% when halos were found bilaterally. Blood-flow abnormal parameters (temporal artery diameter, peak systolic blood-flow velocities, stenoses, occlusions) were common in GCA and non-GCA patients, as well as in healthy and atherosclerotic disease-control, elderly subjects. At follow-up CDS examinations performed at 2 and 4 weeks after initiation of corticosteroid treatment for GCA, halos disappeared in all 18 patients (9 and 9, respectively). We conclude that CDS, an inexpensive, non-invasive, and easy-to-perform method, allows a directional biopsy that has an increased probability to confirm the clinical diagnosis. Biopsy is not necessary in a substantial proportion of patients in whom bilateral halo signs can be found by CDS.

Etiopathogenesis of Behçet's disease with emphasison the role of immunological aberrations

Behçets disease (BD) is a chronic multisystemic inflammatory disorder of unknown origin consisting of oral aphthous ulcers, ocular symptoms, skin lesions, and genital ulcerations. It has many features in common with systemic vasculitides and is more prevalent in countries along the ancient Silk route. Immune-mediated mechanisms play a major role in the pathogenesis of the disease, and inflammatory mediators are also involved. BD is not considered to be an autoimmune disorder, and the character of the disease needs to be clarified. Immunological aberrations in BD have been extensively studied by many investigators; genetic factors have been related to disease susceptibility, but their exact role in the development of disease is uncertain. Environmental factors such as infectious agents have also been implicated in the etiology of BD. However, the etiopathogenesis of the disease remains to be elucidated. Factors involved in the immunopathogenesis of BD with emphasis on the role of immunological aberrations are analyzed in this review.

Arterial Calcifications in β-Thalassemia

The purpose of this study was to define the incidence of arterial calcifications in patients with β-Thalassemia. β-thalassemia patients have been shown to present a high preva lence of angioid streaks and skin lesions characteristic of pseudoxanthoma elasticum (PXE). Given the fact that vascular involvement in the form of arterial calcifications is also a common manifestation of PXE, the authors investigated radiographically the presence of arterial calcifications in β-thalassemia patients. They studied 40 patients with β-thalassemia over 30 years of age. Forty healthy, age- and sex-matched subjects were chosen as a control group. Radiographs of the tibias were performed in order to disclose arterial calcifications. The occurrence of PXE skin lesions and of angioid streaks (AS) was also investigated. Arterial calcifications were detected in the posterior tibial artery in 22 (55%) β-thalassemia patients and in six (15%) controls (P<0.01 for the comparison). PXE skin lesions and AS were found in eight (20%) and 21 (52%) patients respectively. A total of 34 patients (85%) had at least one of the three lesions, namely, arterial calcifications, angioid streaks, and/or PXE-like skin lesions. Stepwise logistic regression analysis did not reveal prognostic value in independent variables such as transfusions, chelation therapy, pseudoxanthoma elasticum skin lesions and/or angioid streaks, diabetes, hemoglobin, serum ferritin, and uric acid. It was concluded that arterial calcifications are common in older β-thalassemia patients. This finding could be a manifestation of an acquired PXE syndrome associated with β-thalassemia, and consequently, vascular events complicating PXE should be expected in these patients.

Pamidronate is superior to ibandronate in decreasing bone resorption, interleukin‐6 and β2‐microglobulin in multiple myeloma

Abstract: Objectives: Bisphosphonates have been found to reduce skeletal events in patients with multiple myeloma (MM). This is the first randomised trial to compare the efficacy of pamidronate and ibandronate, a third‐generation aminobisphosphonate, in bone turnover and disease activity in MM patients. Methods: Patients with MM, stage II or III, were randomly assigned to receive either pamidronate 90 mg (group I: 23 patients) or ibandronate 4 mg (group II: 21 patients) as a monthly intravenous infusion in addition to conventional chemotherapy. Skeletal events, such as pathologic fractures, hypercalcaemia, and bone radiotherapy were analysed. Bone resorption markers [N‐terminal cross‐linking telopeptide of type‐I collagen (NTX) and tartrate‐resistant acid phosphatase type 5b (TRACP‐5b)], bone formation markers (bone alkaline phosphatase and osteocalcin), markers of disease activity (paraprotein, CRP, β2‐microglobulin), and interleukin‐6 (IL‐6) were also studied. Results: In both groups, the combination of chemotherapy with either pamidronate or ibandronate produced a reduction in bone resorption and tumour burden as measured by NTX, IL‐6, paraprotein, CRP, and β2‐microglobulin from the second month of treatment, having no effect on bone formation. TRACP‐5b also had a significant reduction in the pamidronate group from the second month of treatment and in the ibandronate group from the sixth month. However, there was a greater reduction of NTX, IL‐6, and β2‐microglobulin in group I than in group II, starting at the second month of treatment (P = 0.002, 0.001, and 0.004, respectively) and of TRACP‐5b, starting at the fourth month (P = 0.014), that being continued throughout the 10‐month follow‐up of this study. There was no difference in skeletal events during this period. A significant correlation was observed between changes of NTX and changes of TRACP‐5b, IL‐6, and β2‐microglobulin from the second month for patients of both groups. Conclusions: These results suggest that a monthly dose of 90 mg of pamidronate is more effective than 4 mg of ibandronate in reducing osteoclast activity, bone resorption, IL‐6, and possibly tumour burden in MM. TRACP‐5b has also proved to be a useful new marker for monitoring bisphosphonates treatment in MM.

Raynaud's phenomenon is correlated with elevated systolic pulmonary arterial pressure in patients with systemic lupus erythematosus:

In patients with Systemic lupus erythematosus (SLE), Raynaud phenomenon (RP) is frequently present and associated with pulmonary hypertension (PHT). Elevated pulmonary artery systolic pressure (PASP) is an indicator of PHT and can be estimated noninvasively. We attempt to explore the significance of RP in SLE and to correlate it with clinical and serological parameters of the disease. The study population consisted of 34 patients (age, sex and disease duration matched) who fulfilled the revised SLE criteria of the American College of Rheumatology, and were categorized into two groups: Group 1 had patients having SLE and RP (2 males/15 females, mean age 45 ± 18 years) and group 2 had patients with SLE but without RP (3 males/14 females, mean age 40 ± 14 years. Detailed cardiac ultrasound was performed including measurement of PASP, while clinical and serological features of both groups were collected and correlated. Significant differences were shown in the presence of arterial hypertension (P < 0.05), arthralgias (P < 0.005), arthritis (P < 0.05), myalgias (P < 0.05), alopecia (P < 0.05) and PASP (P < 0.0001). No difference was observed among the cardiac ultrasound indices and the ejection fraction between the two groups. PASP was significantly correlated with RP, while no correlation was observed regarding the disease duration. In patients with SLE, the presence of RP was associated with elevation in PASP. Further investigation is needed to clarify the significance of this relation. Lupus (2007) 16, 505—508.

The association of systemic lupus erythematosus and myasthenia gravis.

Two women with the rare association of systemic lupus erythematosus (SLE) and myasthenia gravis (MG) are reported. The first patient developed SLE (arthritis, severe thymectomy for MG. The second patient developed SLE (oral ulcers, arthritis, serositis, leukopenia, high titres of anti-DNA and anti-nuclear antibodies) 4 years prior to the clinical and serological onset of MG. Lymphocyte subsets and in vitro proliferative responses of peripheral blood mononuclear cells to mitogens were normal in both patients. A review of the literature revealed 26 additional patients with definite SLE coexisting with MG. Besides the theoretical interest of this association, the differential diagnosis of fatigue in patients with SLE should always include the possibility of MG.

Adalimumab or Cyclosporine as Monotherapy and in Combination in Severe Psoriatic Arthritis: Results from a Prospective 12-month Nonrandomized Unblinded Clinical Trial

Objective. To assess the efficacy and safety of adalimumab or cyclosporine (CYC) as monotherapy or combination therapy for patients with active psoriatic arthritis (PsA), despite methotrexate (MTX) therapy. Methods. A prospective 12-month, nonrandomized, unblinded clinical trial of 57, 58, and 55 patients who received CYC (2.5–3.75 mg/kg/day), adalimumab (40 mg every other week), or combination, respectively. Lowering of concomitant nonsteroidal antiinflammatory drugs (NSAID) and corticosteroids and reductions of adalimumab and/or CYC doses in responding patients were not restricted. Results. Mean numbers of tender/swollen joints at baseline were 9.7/6.7 in CYC-treated, 13.0/7.8 in adalimumab-treated, and 14.5/9.4 in combination-treated patients, indicating lesser disease severity of patients assigned to the first group. The Psoriatic Arthritis Response Criteria at 12 months were met by 65% of CYC-treated (p = 0.0003 in favor of combination treatment), 85% of adalimumab-treated (p = 0.15 vs combination treatment), and 95% of combination-treated patients, while the American College of Rheumatology-50 response rates were 36%, 69%, and 87%, respectively (p < 0.0001 and p = 0.03 in favor of combination treatment). A significantly greater mean improvement in Health Assessment Questionnaire Disability Index was achieved by combination treatment (−1.11) vs CYC (−0.41) or adalimumab alone (−0.85). Combination therapy significantly improved Psoriasis Area and Severity Index-50 response rates beyond adalimumab, but not beyond the effect of CYC monotherapy. Doses of NSAID and corticosteroids were reduced in combination-treated patients; CYC doses and frequency of adalimumab injections were also reduced in 51% and 10% of them, respectively. No new safety signals were observed. Conclusion. The combination of adalimumab and CYC is safe and seemed to produce major improvement in both clinical and serological variables in patients with severely active PsA and inadequate response to MTX.

Circulating P- and L-Selectin and T-Lymphocyte Activation in Patients with Autoimmune Rheumatic Diseases

Abstract: Circulating levels of P- and L-selectins and the degree of T-lymphocyte activation were assessed by enzyme-linked immunosorbent assays in 75 selected patients with rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) at various clinical stages, and in 40 healthy blood donors matched for age and gender. Mean levels of P-selectin were significantly higher than normal in RA (lower in patients with clinical remission) and SSc (higher in patients with early-onset diffuse disease), but not in SLE. In contrast, mean L-selectin levels were significantly higher than normal in SLE (no correlation to the degree of disease activity), but not in RA or SSc. Mean levels of soluble interleukin-2 receptors (sIL-2R), reflecting mainly T-lymphocyte activation, in patients with active RA, SSc and SLE were almost double the normal level; however, correlations between individual levels of circulating P- or L-selectins and sIL-2R within groups revealed a strong positive correlation only between L-selectin and sIL-2R (r= 0.66, p<0.001), and only in patients with SLE. Given the different expression of P- and L-selectins, these findings indicate a distinct pattern of immune cell activation in chronic diseases that share an overactivation of T-lymphocytes. The possible clinical value of quantitation of circulating P-selectin in patients with RA and SSc on the one hand, and L-selectin in patients with SLE on the other, should be investigated by prospective studies.

Prognostic factors in advanced stage Hodgkin's lymphoma: the significance of the number of involved anatomic sites.

Abstract: Background: Advanced Hodgkins lymphoma (HL) is curable by conventional chemotherapy in 60–70% of patients. The pretreatment identification of a sizeable subgroup of patients with sufficiently low failure‐free survival (FFS) to be eligible for investigational treatment is necessary. Objectives: To determine the prognostic significance of the number of involved sites (NIS) in patients with advanced HL and its relationship to the International Prognostic Score (IPS). Methods: A retrospective review of patients with advanced HL, defined as Ann Arbor stage (AAS) IB, IIB, III or IV, treated with anthracycline‐based regimens. The end‐point was FFS. Results: We identified 277 patients with a median age of 32 yr (14–78), 57% of whom were males. AAS was I in 4% of patients, II in 29%, III in 38% and IV in 29%. B‐symptoms were recorded in 81%. Most patients had nodular sclerosis (64%) and mixed cellularity (26%) histology. IPS was ≥3 in 44% of 242 evaluable patients. The NIS was ≥5 in 32% of the patients and 20% of all patients had both ≥5 involved sites and IPS ≥3. The 10‐yr FFS was 67%, being 76% vs. 50% for patients with ≤4 vs. ≥5 involved sites (P < 0.0001). The NIS (≥ 5), AAS IV and anemia were independent predictors of FFS in multivariate analysis. The NIS remained significant along with IPS, when the latter was included in the analysis. Patients with ≥5 involved sites and IPS ≥3 had 10‐yr FFS overall, and relapse‐free survival of 41%, 45% and 49%, respectively. Conclusions: The NIS was associated with FFS in advanced HL, was independent of IPS, and led to the identification of a sizeable subgroup of patients with 10‐yr FFS of approximately 40%. This factor should be evaluated during the development of prognostic systems.