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: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations that cannot always be regulated by steroids and immunosuppressive therapy. Intravenous immunoglobulin is an optional immunomodulatory agent for the treatment of SLE[1], but the appropriate indications for its use, duration of therapy and recommended dosage are yet to be established. In SLE patients, most publications report the utilization of a high dose (2 g/kg body weight) protocol.

Objectives: To investigate whether lower doses of IVIg are beneficial for SLE patients.

Methods: We retrospectively analyzed the medical records of 62 patients who received low dose IVIg[2] (approximately 0.5 g/kg body weight).

Results: The treatment was associated with clinical improvement in many specific disease manifestations, along with a continuous decrease in SLEDAI scores (SLE Disease Activity Index). However, thrombocytopenia, alopecia and vasculitis did not improve following IVIg therapy.

Conclusions: Low dose IVIg is a possible therapeutic option in SLE and is associated with lower cost than the high dose regimen and possibly fewer adverse effects.

Background: Infectious agents are important in the pathogenesis of autoimmune disease since they are a major part of the environmental trigger of autoimmunity. A negative relationship between latitude and infectious disease species richness has been suggested.

Objectives: To examine whether their prevalence differs in two latitudinally different populations.

Methods: The prevalence of infections with Toxoplasma gondii, rubella virus, cytomegalovirus, Epstein-Barr virus and Treponema pallidum was compared between subjects from Italy and Colombia.

Results: We found high titers of antibodies against four of five microorganisms tested, Toxoplasma gondii (50.8%), rubella virus (German measles) (75%), cytomegalovirus (86.3%), Epstein-Barr virus (83.3%) and Treponema pallidum (6.3%) in completely healthy individuals from a tropical country (Colombia) and a European country (Italy). Differences between two groups of volunteers were noted regarding two infectious agents. The prevalence of immunoglobulin G anti-rubella antibodies was significantly higher among Italian subjects (85% vs. 67.9%, P = 0.002), whereas antibodies against CMV[1] were less prevalent among Italian as compared to Colombian subjects (77% vs. 92.9%, P < 0.001).

Conclusions: These differences might also result in a different tendency towards development of autoimmune diseases associated with these infectious agents in different populations.

Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by disabling fatigue, difficulty in concentration and memory, and concomitant skeletal and muscular pain. Several mechanisms have been suggested to play a role in CFS[1], such as excessive oxidative stress following exertion, immune imbalance characterized by decreased natural killer cell and macrophage activity, immunoglobulin G subclass deficiencies (IgG-1[2], IgG-3) and decreased serum concentrations of complement component. Autoantibodies were also suggested as a possible factor in the pathogenesis of CFS. Recent studies indicate that anti-serotonin, anti-microtubule-associated protein 2 and anti-muscarinic cholinergic receptor 1 may play a role in the pathogenesis of CFS. It has been demonstrated that impairment in vasoactive neuropeptide metabolism may explain the CFS symptoms

Background: Percutaneous tracheostomy has largely replaced surgical tracheostomy in the intensive care unit setting. Although it seems logical that surgeons continue to do tracheostomies, anesthesiologists and intensive care specialists are familiar with airway control and guide wire techniques and could replace surgeons in the performance of PDT.

Objectives: To assess the safety and effectiveness of bedside PDT[1] in the ICU[2].

Methods: We conducted a retrospective chart review of 207 patients in the ICU who underwent PDT by an intensive care physician.

Results: Subcutaneous emphysema without pneumothorax occurred in one patient. Four patients underwent surgical revision following PDT. Early bleeding (during the first 48 hours following the procedure) was the indication in two patients and late bleeding, on the 10th post-PDT day, in one. In one case PDT was converted to surgical tracheostomy due to inadvertent early decannulation. There was one death directly related to the procedure, due to an unrecognized paratracheal insertion of the tracheostomy tube followed by mechanical ventilation, which led to bilateral pneumothorax, pneumomediastinum and cardio-circulatory collapse. No infectious complications were seen at the stoma site or surrounding tissues.

Conclusions: PDT by intensive care physicians appears to be safe and should be included in the curriculum of intensive care residency.

Background: The imaging parameters that mandate further diagnostic workup in focal asymmetric breast densities are not clearly defined.

Objectives: To identify indications for further workup in FABD[1] by comparing mammographic and ultrasonographic findings with the pathology results of women with FABD.

Methods: Ninety-four women (97 FABD) were referred for core needle biopsy after incidental discovery of FABD on routine mammograms (n=83) or on diagnostic mammograms performed for palpable masses (n=11). Clinical data included patient’s age, use of hormone replacement therapy, family history of breast cancer, and the presence of a palpable mass. Mammograms and sonograms were evaluated for lesion size and location, associated calcifications, architectural distortion, and change from previous examinations when available. Two patient groups emerged according to the pathological findings and the data were compared.

Results: The average age, size and location of the lesions in the malignant (n=5) and benign (n=92) groups were similar. There was a significant difference (P < 0.05) for the presence of a clinically palpable mass (60% vs. 9%, respectively), a cluster of calcifications (60% vs. 12%), associated architectural distortion (exclusively in the malignant group) and a solid mass on sonography (50% vs. 9%). The malignant group had a higher rate of family history of breast cancer and HRT[2] use.

Conclusions: FABD usually present a benign etiology and can safely be managed by follow‑up. The presence of an architectural distortion, a cluster of malignant‑appearing or indeterminate calcifications, a sonographic mass with features of possible malignancy, or a clinically palpable mass mandates tissue diagnosis.

Background: Until three decades ago coronary heart disease and stroke were considered rare in the Israeli Bedouin population. Today, this population shows increasing high prevalence compared to the Jewish population.

Objectives: To evaluate the prevalence of diagnosed cardiovascular risk factors among the Bedouin (hypertension, diabetes mellitus, dyslipidemia), and to assess compliance with follow-up tests and drug treatment.

Methods: The study included all listed patients aged 20 years and older in eight clinics in major Bedouin towns, and in two large teaching clinics in Beer Sheva (Jewish population). Risk factor data were extracted from the clinics' computerized databases. For those diagnosed with hypertension, diabetes or dyslipidemia, drug purchasing data were collected from the pharmacy database to determine compliance with treatment, and from the central laboratory mainframe (HbA1c and low density lipoprotein-cholesterol) to evaluate follow-up and control.

Results: A significantly higher prevalence of diabetes in all age groups was found in the Bedouin population compared to the Jewish population; age-adjusted results show a prevalence of 12% vs. 8% respectively (P < 0.001). The prevalence of dyslipidemia and age-adjusted hypertension was lower among Bedouins (5.8% vs. 18.2%, P < 0.01 and 17% vs. 21%, P < 0.001 respectively). Two-thirds of hypertensive Bedouin patients and 72.9% of diabetic Bedouin patients were not compliant with treatment. For dyslipidemia only 10.4% of the Bedouins were compliant compared with 28.2% in the Jewish population (P < 0.001).

Conclusions: Compliance with drug therapy and follow-up tests was found to be a major problem in the Bedouin population.
 

Background: Crohn's disease and ulcerative colitis are inflammatory bowel diseases with an unknown etiology. Interleukin-18 is a pro-inflammatory cytokine that is up-regulated in Crohn’s disease. IL-18[1] binding protein neutralizes IL-18. The relationship of IL-18 and IL-18BP[2] and disease activity in these diseases is not fully understood.

Objectives: To investigate the correlation of IL-18 and IL-18BP with disease activity and other disease parameters in inflammatory bowel disease.

Methods: IL-18 and IL-18BP isoform α were measured in 129 patients and 10 healthy individuals. Patients' mean age was 40.5 (range 15–70 years) and 43 were women; 58 Crohn's and 28 colitis patients were in remission and 52 and 14, respectively, were in exacerbation. Twenty-three (19 and 4 respectively) were studied in both remission and exacerbation.

Results: The mean level of free IL-18 was significantly different between healthy individuals and Crohn's patients, and between Crohn's patients during exacerbation and remission (167 ± 32 vs. 471 ± 88 and 325 ± 24 pg/ml, respectively, P < 0.05). Mean level of IL-18BP was significantly different between healthy individuals and Crohn patients, and between Crohn patients during exacerbation and remission (2.1 ± 1.1, 7.5 ± 4 and 5.23 ± 2.8 ng/ml, respectively, P < 0.01). In the colitis patients, mean free IL-18 level and IL-18BP were significantly different between healthy individuals and patients, but not between disease remission and exacerbation (167 ± 32, 492 ± 247 and 451± 69 pg/ml for IL-18, and 2.1 ± 1.1, 7.69 ± 4 and 6.8 ± 7 ng/ml for IL-18BP, respectively, P = 0.05).

Conclusions: IL-18 and IL-18BP levels are higher in patients with inflammatory bowel disease compared to healthy individuals. In Crohn's disease, but not in ulcerative colitis, IL-18 (but not free IL-18) and IL-18BP levels are significantly higher during exacerbation compared to remission. This observation highlights the importance of IL-18 in the pathogenesis of inflammatory bowel diseases, especially in Crohn's disease.