Israel Medical Association Journal

Objectives: To assess the changes in ACPA titers in patients with RA after treatment with infliximab as a first biological agent, and to correlate these variations with non-infusion-related adverse effects.

Methods: In a prospective multicenter observational study involving 48 research centers, we assessed 139 patients with established moderate-to-severe RA diagnosed according to American College of Rheumatology criteria. Samples were collected before and 6–12 months after treatment.

Results: The mean age of the study patients was 50.6 years old, and 118 were female (84.9%). Statistically significant variations in ACPA titers were noted in 47 patients (before and after treatment) (P = 0.012). Overall, ACPA titers were decreased in 32 (65.3%) and increased in 15 (34.7%). No correlation was found between severe or mild adverse effects in patients presenting variations in ACPA titers.

Conclusions: The present study showed that infliximab affected ACPA titers, promoting mainly a decrease; however, this was not related to the occurrence of non-infusion-related adverse effects.

Objectives: To assess the relationship between sleep deprivation, key metabolic markers, and professional performance in medical residents.

Methods: We compared 35 residents working the in-house night shift with 35 senior year medical students in a cross-sectional cohort study. The Epworth Sleepiness Scale (ESS) questionnaire was administered and blood tests for complete blood count (CBC), blood chemistry panel, lipid profile and C-reactive protein (CRP) were obtained from all participants.

Results: Medical students and medical residents were comparable demographically except for age, weekly working hours, reported weight gain, and physical activity. The ESS questionnaires indicated a significantly higher and abnormal mean score and higher risk of falling asleep during five of eight daily activities among medical residents as compared with medical students. Medical residents had lower high density lipoprotein levels, a trend towards higher triglyceride levels and higher monocyte count than did medical students. CRP levels and other laboratory tests were normal and similar in both groups. Among the medical residents, 5 (15%) were involved in a car accident during residency, and 63% and 49% reported low professional performance and judgment levels after the night shift, respectively.

Conclusions: Medical residency service was associated with increased sleepiness, deleterious lifestyle changes, poorer lipid profile, mild CBC changes, and reduced professional performance and judgment after working the night shift. However, no significant changes were observed in CRP or in blood chemistry panel. Larger prospective cohort studies are warranted to evaluate the dynamics in sleepiness and metabolic factors over time.

Background: Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Q pyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change, imposed by this mutation on pyrin structure, may help to understand the role of this mutation

Objectives: To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein.

Methods: The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined.

Results: The E148Q mutation caused deviation from the wild-type pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%.

Conclusions: A quantum-chemistry based model suggests that the structural effect of the E148Q mutation is indeed low, but not zero. 
 

Background: Fat tissue mediates the production of inflammatory cytokines and oxidative products, which are key steps in the development of type 2 diabetes and atherosclerosis. Antioxidant-rich diets protect against chronic diseases, but antioxidants may interfere with pro-inflammatory signals.

Objectives: To investigate the effect of the potent tomato-derived antioxidant carotenoid, lycopene, on plasma antioxidants (carotenoids and vitamin E), inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha), and oxidation products (conjugated dienes).

Methods: Eight obese patients (body mass index 37.5 ± 2.5 kg/m²) were compared with a control group of eight lean, age and gender-matched subjects (BMI[1] 21.6 ±  0.6 kg/m²), before and after 4 weeks of lycopene supplementation (tomato-derived Lyc-O-Mato) (30 mg daily).

Results: Plasma carotenoids were significantly reduced in the obese compared to control subjects (0.54 ± 0.06 vs. 0.87 ± 0.08 mg/ml, P < 0.01). CRP[2] levels were significantly higher (6.5 vs. 1.1 mg/L, P = 0.04) in obese vs. controls, as were IL-6[3] and conjugated dienes (3.6 and 7.9-fold, respectively). CRP, IL-6 and conjugated dienes correlated with BMI, while IL-6 and conjugated dienes correlated inversely with carotenoids (P < 0.05). Following lycopene treatment, a significant elevation of plasma carotenoids (1.79 vs. 0.54 ug/ml) and specifically lycopene (1.15 vs 0.23 ug/ml) (P < 0.001) occurred in the treatment vs. placebo group, respectively. Markers of inflammation and oxidation products were not altered by lycopene.
Conclusions: Obese patients showed abnormally higher markers of inflammation and oxidation products and lower plasma carotenoids. The lack of reduction of pro-inflammatory markers could be attributed to the short period of the study and the small number of participants. More studies are needed on the protective qualities of natural antioxidant-rich diets against obesity-related co-morbidities.

Background: High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP[1] levels and association with other markers of inflammation in patients with stable CAD[2] on aggressive statin therapy is unknown.

Objectives: To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.

Methods: Levels of hs-CRP were measured twice within 14 days (7 ± 4) in 23 patients (22 males and 1 female, average age 66 ± 10 years) with stable CAD and hs-CRP ≥ 2.0 mg/L but ≤ 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 ± 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.

Results: hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8–11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0–9.7 mg/L; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P = 0.4353). Of the cytokines tested, only the anti-inflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above lower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).

Conclusions: In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.

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.