benign paroxysmal peritonitis [keywords]
- Recurrent pericarditis in children and adolescents: a multicentre cohort study. [JOURNAL ARTICLE]
- J Cardiovasc Med (Hagerstown) 2016 Sep; 17(9):707-712.
Limited data are available about recurrent pericarditis in children. We sought to explore contemporary causes, characteristics, therapies and outcomes of recurrent pericarditis in paediatric patients.A multicentre (eight sites) cohort study of 110 consecutive cases of paediatric patients with at least two recurrences of pericarditis over an 11-year period (2000-2010) [median 13 years, interquartile range (IQR) 5, 69 boys].Recurrences were idiopathic or viral in 89.1% of cases, followed by postpericardiotomy syndrome (9.1%) and familial Mediterranean fever (0.9%). Recurrent pericarditis was treated with nonsteroidal anti-inflammatory drugs (NSAIDs) in 80.9% of cases, corticosteroids in 64.8% and colchicine was added in 61.8%. Immunosuppressive therapies were administered in 15.5% of patients after subsequent recurrences. After a median follow-up of 60th months, 528 subsequent recurrences were recorded (median 3, range 2-25). Corticosteroid-treated patients experienced more recurrences (standardized risk of recurrence per 100 person-years was 93.2 for patients treated with corticosteroids and 45.2 for those without), side effects and disease-related hospitalizations (for all P < 0.05). Adjuvant therapy with colchicine was associated with a decrease in the risk of recurrence from 3.74 per year before initiation of colchicine to 1.37 per year after (P < 0.05). Anakinra therapy (n = 12) was associated with a drop in the number of recurrences from 4.29 per year before to 0.14 per year after (P < 0.05). Transient constrictive pericarditis developed in 2.7% of patients.Recurrent pericarditis has an overall favourable prognosis in children, although it may require frequent readmissions and seriously affect the quality of life, especially in patients treated with corticosteroids. Colchicine or anakinra therapies were associated with significant decrease in the risk of recurrence.
- MEFV gene variation R202Q is associated with metabolic syndrome. [JOURNAL ARTICLE]
- Eur Rev Med Pharmacol Sci 2016 Jul; 20(15):3255-3261.
MEFV (Mediterranean fever) gene encoding pyrin regulates inflammatory responses. It has been shown that MEFV gene variations are associated with higher acute phase responses and altered course in the different inflammatory diseases. MEFV gene variations may affect the course of metabolic syndrome components.This study included 50 patients with metabolic syndrome and 50 unrelated healthy controls. Genomic DNAs were isolated from patients and healthy controls with standard methods and analysis of exon 2 and 10 of MEFV gene was performed by using Sanger sequencing method.The MEFV gene variations were detected in 21 patients with metabolic syndrome (42%) and 12 healthy controls (24%) (p=0.55). The frequency of MEFV gene variations with high penetrance (i.e. M694V, M680I, V726A) was similar between patients and healthy controls (p>0.05). We found that R202Q was more frequent in the patient group (n=11 [22%] vs. n=3 [6%]) and associated with metabolic syndrome (p: 0.021; OR: 4.42; CI95%: 1.15-16.97). When patients with and without MEFV gene variations were compared, no significant difference was found in laboratory and clinical parameters.To best of our knowledge, this is the first study indicating an association between MeS and R202Q mutation of MEFV gene. Familial Mediterranean fever (FMF) related MEFV gene variations may contribute to the pathogenesis of metabolic syndrome.
- Unusual presentation of familial Mediterranean fever: atypical hyperemic recurrent skin lesions. [JOURNAL ARTICLE]
- Clin Exp Rheumatol 2016 Jul 27.
- Familial Mediterranean fever patients homozygous for E148Q variant. [JOURNAL ARTICLE]
- Int J Rheum Dis 2016 Jul 26.
Familial Mediterranean fever (FMF) results from MEFV gene mutations. E148Q is a variant of unknown significance in MEFV. We aimed to define characteristics of FMF patients homozygous for E148Q, check for other MEFV variants in a subgroup, and compare the characteristics with FMF patients carrying other mutations.Thirty FMF patients homozygous for E148Q were reviewed. MEFV variant analysis was performed with strip assay. All MEFV exons were screened by direct DNA sequencing in 14 randomly selected E148Q/E148Q patients. E148Q was also checked in 100 healthy adolescents. We compared the characteristics of FMF patients between three groups: E148Q/E148Q (n = 30), M694V/E148Q (n = 19) and exon 10/exon 10 MEFV mutations (n = 48).Among 30 FMF patients (E148Q/E148Q), the median age at disease onset and diagnosis were 60 (12-168) and 94 (41-196) months, respectively. Fifteen (50%) patients had mild, 14 (46.7%) moderate and one (3.3%) had severe disease. Twenty-two (73.3%) patients had complete, seven (23.3%) had incomplete response to colchicine, while only one was unresponsive. The detected MEFV variants in 14 E148Q/E148Q FMF patients were as follows: R314R (n = 9; 64.3%), E474E (n = 13; 92.9%), Q476Q (n = 13; 92.9%), D510D (n = 13; 92.9%), and P588P (n = 8; 57.1%). The E148Q allele frequency was 6.5% in healthy adolescents. When compared to FMF patients with other MEFV mutations, disease onset was later, disease was less severe and the ratio of patients responding completely to colchicine was higher in E148Q/E148Q patients.Patients homozygous for E148Q and negative for other pathogenic MEFV variants may display FMF phenotype and may experience moderate/severe disease activity, although the disease may be milder when compared to FMF patients with other mutations.
- A novel colchicine-based microtubule inhibitor exhibits potent antitumor activity by inducing mitochondrial mediated apoptosis in MIA PaCa-2 pancreatic cancer cells. [JOURNAL ARTICLE]
- Tumour Biol 2016 Jul 24.
Colchicine, an antimitotic alkaloid isolated from Colchicum autumnale, is a classical drug for treatment of gout and familial Mediterranean fever. It causes antiproliferative effects through the inhibition of microtubule formation, which leads to mitotic arrest and cell death by apoptosis. Here, we report that a novel colchicine analog, 4o (N-[(7S)-1,2,3-trimethoxy-9-oxo-10-[3-(trifluoromethyl)-4-chlorophenylamino]-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide), which exhibited potent anticancer activities both in vitro and in vivo. In this study, 4o with excellent pharmacokinetic profile and no P-gp induction liability displayed strong inhibition of proliferation against various human cancer cell lines. However, pancreatic cancer cell line MIA PaCa-2 was found to be more sensitive towards 4o and showed strong inhibition in concentration and time-dependent manner. By increasing intracellular reactive oxygen species (ROS) levels, 4o induced endoplasmic reticular stress and mitochondrial dysfunction in MIA PaCa-2 cells. Blockage of ROS production reversed 4o-induced endoplasmic reticulum (ER) stress, calcium release, and cell death. More importantly, it revealed that increased ROS generation might be an effective strategy in treating human pancreatic cancer. Further 4o treatment induced mitotic arrest, altered the expression of cell cycle-associated proteins, and disrupted the microtubules in MIA PaCa-2 cells. 4o treatment caused loss of mitochondrial membrane potential, cytochrome c release, upregulation of Bax, downregulation of Bcl-2, and cleavage of caspase-3, thereby showing activation of mitochondrial mediated apoptosis. The in vivo anticancer activity of the compound was studied using sarcoma-180 (ascitic) and leukemia (P388 lymphocytic and L1210 lymphoid) models in mice and showed promising antitumor activity with the least toxicity unlike colchicine. Such studies have hitherto not been reported. Taken together, these findings highlighted that 4o, a potent derivative of colchicine, causes tumor regression with reduced toxicity and provides a novel anticancer candidate for the therapeutic use.
- The Relationship Between Atherogenic Index and Carotid Artery Atherosclerosis in Familial Mediterranean Fever: A Pilot Study. [JOURNAL ARTICLE]
- Angiology 2016 Jul 19.
Familial Mediterranean fever (FMF) is a disease characterized by chronic inflammation. Atherogenic index of plasma (AIP) is a logarithmic value of the triglyceride to high-density lipoprotein cholesterol ratio and it is a good marker for atherosclerotic heart disease and cardiac risk. In this study, we investigated subclinical atherosclerosis and cardiac risks in patients with FMF. Patients with FMF (78 men and 84 women) and healthy controls (74 men and 82 women) were included in this study. The AIP values of the patients were calculated and carotid intima-media thicknesses (cIMTs) were measured. The cIMT (P < .001) and AIP (P < .001) values of patients with FMF were higher than the values of the control group. There was a positive correlation between cIMT and AIP values (r = .304, P < .001). In regression analysis, we detected an independent relationship between cIMT and AIP (β = .248, P = .001). Atherogenic index of plasma may be highly correlated with the subclinical atherosclerosis. Particularly, male patients with FMF may have a high cardiac risk.
- The evaluation of renal hemodynamics changes in Familial Mediterranean fever with color Doppler sonography. [JOURNAL ARTICLE]
- Ren Fail 2016 Jul 17.:1-6.
Renal resistive index (RRI) scanned through renal Doppler is a practical marker employed in measuring blood flow in renal and intrarenal arteries and in noninvasive evaluation of renal vascular resistance. We aimed to investigate the renal hemodynamic variations in patients with Familial Mediterranean Fever (FMF).Seventy-nine FMF patients and 51 healthy subjects suitable for age and sex were included. Patients were divided into two groups according to their urinary albumin excretion. Fifty-two patients with 0-29 mg/day albuminuria were included in the normoalbuminuric group while 27 patients with 30-299 mg/day albuminuria were included in the microalbuminuric group.RRI values were higher in patients with FMF compared to the healthy subjects (p < 0.0001). Additionally, RRI values were found to be higher in the microalbuminuric patients group compared to the normoalbuminuric patients group, and RRI values were also higher in normoalbuminuric patients group compared to the control group (p = 0.002, p < 0.0001). The ROC curve analysis suggested that the optimum RRI cutoff value for microalbuminuria in patients was 0.63, sensitivity of 66%, specificity of 60%, and p = 0.013.RRI may be a marker that may be used in assessing resistance to renal blood flow, early renal damage, and progression of renal damage in FMF patients.
- DNA demethylation of inflammasome-associated genes is enhanced in patients with cryopyrin-associated periodic syndromes. [JOURNAL ARTICLE]
- J Allergy Clin Immunol 2016 Jul 6.
Inflammasomes are cytosolic multiprotein complexes in macrophages. They assemble after infection- or stress-associated stimuli, activating both caspase-1-mediated inflammatory cytokine secretion and pyroptosis. Increased inflammasome activity resulting from gene mutations is related to monogenic autoinflammatory syndromes. However, variable penetrance among patients with the same gene mutations suggests involvement of additional mechanisms associated with inflammasome gene regulation.We sought to investigate the role of DNA demethylation in activating inflammasome genes during macrophage differentiation and monocyte activation in healthy control subjects and patients with autoinflammatory syndrome.Inflammasome-related genes were tested for DNA methylation and mRNA levels by using bisulfite pyrosequencing and quantitative RT-PCR in monocytes in vitro differentiated to macrophages and exposed to inflammatory conditions. The contribution of Tet methylcytosine dioxygenase 2 (TET2) and nuclear factor κB to DNA demethylation was tested by using chromatin immunoprecipitation, small interfering RNA-mediated downregulation, and pharmacologic inhibition.We observed that inflammasome-related genes are rapidly demethylated in both monocyte-to-macrophage differentiation and on monocyte activation. Demethylation associates with increased gene expression, and both mechanisms are impaired when TET2 and nuclear factor κB are downregulated. We analyzed DNA methylation levels of inflammasome-related genes in patients with cryopyrin-associated periodic syndromes (CAPS) and familial Mediterranean fever, 2 archetypical monogenic autoinflammatory syndromes. Under the above conditions, monocytes from untreated patients with CAPS undergo more efficient DNA demethylation than those of healthy subjects. Interestingly, patients with CAPS treated with anti-IL-1 drugs display methylation levels similar to those of healthy control subjects.Our study is the first to demonstrate the involvement of DNA methylation-associated alterations in patients with monogenic autoinflammatory disease and opens up possibilities for novel clinical markers.
- Familial mediterranean fever treated with anakinra: A case report. [LETTER]
- Reumatol Clin 2016 Jul 1.
- Evaluation of cochlear functions in children with Familial Mediterranean Fever. [Journal Article]
- Int J Pediatr Otorhinolaryngol 2016 Aug.:139-42.
To evaluate cochlear functions in patients with Familial Mediterranean Fever in relation to the disease severity score and treatment duration.50 patients (4-18 years) who had been followed-up with the diagnosis of FMF and regularly receiving appropriate colchicine treatment and 39 healthy controls were included in the study. All the patients and controls were evaluated by audiologic evaluation, including high-frequency pure-tone audiometry and distortion product otoacoustic emission tests (DPOAE). The disease severity was determined by scoring system developed by Pras et al.Fifty patients (52% female, 48% male; mean age12.2 ± 4.1 years) and 39 controls (58.9% female, 41.1% male, mean age 11.1 ± 3.4 years) were enrolled the study. The pure tone average of FMF patients was significantly higher than that of the control group at 500, 4000, and 8000 Hz frequencies. The patients' DPOAE signal values at 6 kHz, 8 kHz frequencies and SNR values at 8 kHz were significantly higher than control group. The patients' audiometry and DPOAE results were compared with the disease severity scores. Pure tone average was significantly higher in severe and moderate patient groups compared to the mild patient group at 2000 Hz frequency. DPOAE signal values showed statistically significant differences between the patient severity scores at 1.4 and 2.8 kHz frequencies. The mean colchicine treatment duration was found to be 5.1 ± 3.7 years. There were significant differences at 250 and 500 Hz frequencies when patients' audiometry results were compared with the treatment periods.FMF affects cochlear functions particularly at high frequencies.