Ischemic heart disease and rheumatoid arthritis: Do inflammatory cytokines have a role?

BACKGROUND: The increase in Rheumatoid arthritis (RA) associated mortality is predominantly due to accelerated coronary artery and cerebrovascular atherosclerosis with increased risk of ischemic heart disease about 50% in RA patients compared to controls. OBJECTIVE: To study the pathogenesis of ischemic heart disease in RA, role of inflammatory cytokine interplay, disease activity and rheumatoid factor positivity. METHODS: Eighty RA patients and 44 healthy controls were included. All subjects were younger than 45years for females and 55years for males with exclusion of all traditional risk factors for atherosclerosis. Interleukin (IL) 1, 6 and 18 were assessed in all subjects. RA patients fulfilled ACR/EULAR 2010 criteria and were subjected to Dobutaminestress-echocardiography, diseases activity assessed by DAS-28, X-ray hands for Larsen score and function assessment by HAQ. RESULTS: RA patients had significantly higher serum IL 1, 6 and 18 than controls (p=0.00 in all). Thirty four (42.5%) patients had hypertensive reaction on Dobutamine-stress-echocardiography, four of them had ischemic change, and 46 (57.5%) had normal reaction. All patients with hypertensive reaction had positive RF (p=0.00), 10 had DAS-28>5.1, 20 had DAS-28 from 3.2 to5.1 and 4 were in remission (p=0.001). CRP was higher in patients with hypertensive reaction (p=0.003) while serum levels of IL1, 6 and 18 showed no significant difference. In all patients, serum levels of IL1, 6 and 18 showed significant positive correlation with VAS, HAQ and DAS-28 (p<0.001 in all). Only IL18 showed significant positive correlation with X-ray score in all patients. CONCLUSION: Disease activity and RF positivity play an important risk factor for ischemic heart disease in RA. Serum levels of IL1, 6 and 18 did not help much in detecting patients at risk of ischemic heart disease. Better control of RA disease activity with early remission helps in preventing cardiac complications. More studies on larger number of patients are needed for better understanding of mechanism of ischemic heart disease in RA.

The association between pentraxin 3 in maternal circulation and pathological intrauterine fetal growth restriction.

OBJECTIVE: To assess the diagnostic accuracy of maternal serum pentraxin 3 (PTX3) in identifying pathological intrauterine fetal growth restriction (IUFGR) among women presented in the third trimester of pregnancy with a small for gestational age (SGA) fetus. STUDY DESIGN: This case control study was conducted in Ain-Shams University Maternity Hospital, Abbasiya Square, Cairo, Egypt and included women diagnosed at the third trimester of pregnancy as having a SGA fetus. Cases included pregnant women with pathological IUFGR, while women with physiologically SGA fetus were included in the control group. Diagnosis of antenatal SGA fetus was based on the presence of abdominal circumference <10th percentile. Pathological IUFGR was provisionally diagnosed antenatally by the presence of falling percentiles on serial ultrasound scans and then the definitive diagnosis was established postnatally after comprehensive neonatal evaluation. Maternal venous blood samples were collected from the eligible participants, once at the time of enrollment, to assess serum PTX3 levels using enzyme-linked immunosorbent assay (ELISA). Both groups were then followed up till delivery to confirm the diagnosis. RESULTS: Among the 68 pregnant included in the study, PTX3 was found to be significantly elevated in women with SGA fetus due to pathological IUFGR (n=34) than those with physiologically SGA fetus (n=34) [6.5 ng/ml (2.5-11.0) versus 1.2 ng/ml (0.8-2.5) respectively], with a best cutoff value of ≥1.3 ng/ml [sensitivity of 85.3% (95% confidence interval (CI), 68.9-95.0) and a specificity of 73.5% (95% CI, 55.6-87.1)]. Using multivariable binary logistic regression model, amniotic fluid index (AFI) (P=0.010), estimated fetal weight (EFW) (P=0.016), PTX3 level (P=0.041), and umbilical artery pulsatility index (UA-PI) (P=0.027) were all found to be independent diagnostic markers for pathological IUFGR. CONCLUSION: PTX3 is a promising marker that deserves further evaluation as it may differentiate normal and abnormal fetal growth among women presenting at third trimester of pregnancy with a SGA fetus.

[Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients]. / Níveis de óxido nítrico mais elevados estão associados à atividade da doença em pacientes egípcios com artrite reumatoide.

BACKGROUND: Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage. OBJECTIVES: To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity. METHODS: 80 patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method. RESULTS: A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean±SD 82.38±20.46) in comparison to patients without active disease (35.53±7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I. CONCLUSION: There are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status.

Níveis de óxido nítrico mais elevados estão associados à atividade da doença em pacientes egípcios com artrite reumatoide / Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients

Introdução O estresse oxidativo produzido no interior de articulações inflamadas pode produzir fenômenos autoimunes e destruição articular. As espécies radicais com atividade oxidativa, incluindo espécies reativas de nitrogênio, representam mediadores de inflamação e de lesão cartilaginosa. Objetivos Avaliar o óxido nítrico sérico como marcador de estresse oxidativo em pacientes egípcios com artrite reumatoide e sua relação com a atividade da doença. Métodos 80 com artrite reumatoide foram divididos em dois grupos, de acordo com a pontuação DAS28: Grupo I: 42 pacientes com doença ativa, e Grupo II: 38 pacientes com doença inativa. Quarenta indivíduos equiparados por idade e gênero foram incluídos como grupo controle (Grupo III). Foram realizados exames laboratoriais de rotina e o óxido nítrico foi medido usando Elisa. Radiografias simples das mãos foram feitas para a pontuação do estado radiológico utilizando o método de Sharpe. Resultados A comparação do nível sérico de óxido nítrico entre os três grupos mostrou uma diferença altamente significativa (p < 0,001). Obtiveram-se níveis significativamente mais elevados entre os pacientes com artrite reumatoide em comparação com os controles. Os níveis mais elevados foram obtidos em pacientes com a doença ativa (média±DP 82,38±20,46) em comparação com aqueles com a doença inativa (35,53±7,15). O óxido nítrico no Grupo I exibiu uma correlação positiva significativa com a rigidez matinal (r=0,45), artrite (r=0,43), contagem de plaquetas (r=0,46), velocidade de hemossedimentação (r=0,83), proteína C-reativa (r=0,76) e Índice de Atividade de Doença (r=0,85). O óxido ...

Background Oxidative stress generated within inflammatory joints can produce autoimmune phenomena and joint destruction. Radical species with oxidative activity, including reactive nitrogen species, represent mediators of inflammation and cartilage damage. Objectives To assess serum nitric oxide as a marker of oxidative stress in Egyptian patients with rheumatoid arthritis and its relation to disease activity. Methods Eighty patients with rheumatoid arthritis were divided into 2 groups, according to the DAS-28 score: Group I: 42 patients with disease activity, and Group II: 38 patients with no disease activity. Forty age- and sex-matched individuals were included as control group (Group III). Routine laboratory investigations were done, and nitric oxide was measured using Elisa. Hand plain radiographies were done for radiological status scoring using the Sharp method. Results A comparison between nitric oxide in all three groups showed a highly significant difference (p < 0.001), significantly higher levels were obtained among rheumatoid arthritis patients in comparison to controls, and higher levels were obtained in patients with active disease (mean±SD 82.38±20.46) in comparison to patients without active disease (35.53±7.15). Nitric oxide in Group I showed a significant positive correlation with morning stiffness (r=0.45), arthritis (r=0.43), platelet count (r=0.46), erythrocyte sedimentation rate (r=0.83), C-reactive protein (r=0.76) and Disease Activity Score (r=0.85). Nitric oxide showed a significant positive correlation (r=0.43) with hand radiographies (Sharp score) in Group I. Conclusion There are increased levels of nitric oxide in the serum of patients with rheumatoid arthritis. Nitric oxide correlates significantly with disease activity, inflammatory markers and radiological joint status. .

Assessment of ovarian stromal blood flow after metformin treatment in women with polycystic ovary syndrome.

PURPOSE: To authenticate the effect of metformin treatment on ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS) using 3-dimensional (3D) power Doppler. METHODS: The current case-control study was conducted at Ain Shams University Maternity Hospital. A total of 60 women diagnosed to have PCOS were included as group 1. Another 40 fertile women who were recruited from outpatient clinic for contraception without PCOS with regular menstrual cycles were included as control group (group 2). All women underwent 3D power Doppler evaluations of ovarian stroma. Anthropometric, hormonal and biochemical criteria were also measured. All women in group 1 received metformin hydrochloride 500 mg tablets, which were started in a step-up maneuver every 5 days, from one to three tablets per day. The same parameters were also measured after the 3 months duration of treatment. RESULTS: A total of 100 women were finally analyzed. At the start of the study, there were no statistically significant differences between group 1 and group 2 and regarding age and body mass index, but the waist/hip ratio and Ferriman-Gallwey scoring were statistically different between the 2 groups. The mean ovarian volume and stromal volume were significantly larger in group 1. 3D power Doppler indices [the vascularization index (VI), the flow index (FI) and the (VFI) vascularization-flow index] were much higher in group 1 than in group 2 (1.38 ± 0.76 vs. 4.69 ± 1.37, P < 0.05, 26.59 ± 2.26 vs. 32.66 ± 4.37, P < 0.05, and 0.76 ± 0.39 vs. 1.54 ± 0.69, P < 0.05, respectively). After 3 months of using metformin in normal weight PCO women, there was a statistically significant improvement in group 1 regarding, hirsutism, most of hormonal measurements. Also 3 months metformin treatment significantly reduce VI, FI and VFI (4.69 ± 1.37 vs. 2.95 ± 1.52, P < 0.05, 32.66 ± 4.37 vs. 29.48 ± 4.98, P < 0.05 and 1.54 ± 0.69 vs. 1.21 ± 0.7 P < 0.05, respectively). Using Receiver operator characteristic, there was no cut-off value of VI, FI or VFI to detect ovulation in women of PCOS. CONCLUSIONS: Metformin seems to have a beneficial effect in normal weight PCO women via correcting ovarian stromal blood flow and hormonal profiles.

First trimester assessment of pentraxin-3 levels in women with primary unexplained recurrent pregnancy loss.

OBJECTIVE: To evaluate the potential role of measuring first-trimester maternal Pentraxin-3 levels in patients with primary unexplained recurrent pregnancy loss. STUDY DESIGN: A case control study was conducted in Ain Shams University Maternity Hospital. Cases included 45 women with primary unexplained recurrent pregnancy loss and early pregnancy failure admitted for medical or surgical termination of pregnancy. Controls (45 women) included a matched group of apparently healthy pregnant women who had at least one previous uneventful pregnancy with no previous obstetric history of adverse pregnancy outcomes. Maternal venous blood samples were collected for assay of Pentraxin-3 using enzyme-linked immunosorbent assay. The main outcome measure was the pregnancy outcome in women with elevated Pentraxin-3 levels. RESULTS: 90 participants were statistically analyzed. In the patient group, the mean Pentraxin-3 level was 12.00 ± 4.07 ng/ml, while in the control group it was 1.69 ± 0.91 ng/ml. The difference was statistically significant (p<0.001). In the patient group, Pentraxin-3 showed a significant positive correlation with the number of previous miscarriages (p=0.038). CONCLUSION: Abnormally elevated Pentraxin-3 levels indicate the presence of an abnormally exaggerated intrauterine inflammatory or innate immune response that may cause pregnancy failure in women with primary unexplained recurrent pregnancy loss.