Histopathological changes in the infrapatellar fat pad in an experimental rabbit model of early patellofemoral osteoarthritis

Background

The purpose of this study was to characterise the histopathological changes in the infrapatellar fat pad (IPFP) in the early stage of patellofemoral osteoarthritis (PFOA).

Exhaled breath condensate pH in patients with cystic fibrosis

Objective and design

Exhaled breath condensate (EBC) pH has been proposed as a useful, non-invasive marker of airway inflammation in pulmonary diseases. In this study we tested whether cystic fibrosis (CF) is associated with acidification of EBC, when pH is assessed by the CO₂ gas standardization method.

Methods

EBC was collected using two different devices (EcoScreen and R-Tube) in 46 stable CF patients during routine clinical visits and in 28 healthy controls.

Results

Mean EBC pH in CF patients and in healthy controls was similar (EcoScreen: CF patients: 6.38?±?0.03 versus controls: 6.39?±?0.03, p?=?0.699; R-tube: CF patients: 5.94?±?0.04 versus controls: 6.02?±?0.03, p?=?0.159). Inflammatory cell counts in spontaneously expectorated sputum obtained in a subset of patients (n?=?20) showed no correlation with pH values. EBC samples collected with the R-tube were more acidic than those collected with the EcoScreen device (p?Conclusions Our data suggest that EBC pH does not discriminate between healthy controls and those with CF disease indicating that the clinical applicability of EBC pH measurements for assessing airway inflammation in CF is limited.     

Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

Poor Sleep Quality is Associated with Depressive Symptoms in Patients with Heart Disease

Background

Depression in cardiac patients has gained importance due to increased mortality. Although sleep disturbances are a core symptom of depression, the prevalence and patterns of sleep disturbances in heart disease have hardly been examined regarding depression.

Purpose

This cross-sectional study aims to examine sleep disturbances and depressive symptoms in consecutively admitted cardiac patients and depressed patients.

Methods

Two hundred four inpatients (113 male, 91 female) were examined: 94 cardiac inpatients (mean age 49.3?±?14.3?years) with different heart diseases and 110 psychiatric inpatients (mean age 41.6?±?13.0?years) with depressive disorders (DP). A depressive episode according to International Classification of Diseases (ICD)-10 was also diagnosed in 14 of the cardiac patients (DCP). The Pittsburgh Sleep Quality Index (PSQI) and the Beck Depression Inventory (BDI) were used to assess subjective sleep quality and severity of depressive symptoms.

Results

Poor sleep quality (PSQI?>?5) was reported in all comorbid DCP (PSQI 12.00?±?3.53, BDI 17.86?±?4.28), in 60% of the 80 non-DCP (PSQI 5.59?±?3.73, BDI 4.47?±?3.07), and in 86.4% of the DP (PSQI 11.76?±?4.77, BDI 27.11?±?10.54). The cardiac inpatients showed a significant correlation between increased depressive symptoms and the PSQI components subjective sleep quality (r?=?0.40) and daytime dysfunction (r?=?0.34). Both sleep components were significant predictors of self-rated depression (R2?=?0.404).

Conclusions

Most cardiac patients experience poor sleep quality. Self-reported sleep disturbances in heart disease could serve as predictors of clinical or subclinical comorbid depression outside of a psychiatric setting in cardiology and other fields, and such patients should be referred to consultation-liaison psychiatry or polysomnography where sleep disorders like sleep apnea are suspected.     

Body Image in Patients with Systemic Lupus Erythematosus

Background

Systemic lupus erythematosus (SLE), a multisystemic disease of young women may be disfiguring and affect physical and emotional health. Body image literature in SLE is scant and controversial.

Purpose

We compared body image-related quality of life in subjects with (n?=?87) and without (n?=?78) SLE and determined its correlates using the body image quality of life inventory (BIQLI).

Method

The tool was self-administered to consenting individuals. Demographic information along with disease activity and damage assessments for SLE patients were obtained. T test, chi square test, correlational, and regression analyses were used to make comparisons.

Results

Mean age (±SD) were 42.4?±?13.1 and 38.7?±?13.2?years for SLE and non-SLE subjects, respectively. Mean (±SD) BIQLI scores were significantly worse in SLE than non-SLE subjects: 19.9?±?33.2 and 41.6?±?24.8 (p?=?0.001). In SLE, BIQLI scores correlated inversely with overall damage, irreversible cutaneous damage, alopecia, and self-reported depression, and directly with age and health status.

Conclusion

Body image in SLE is poor, and effective interventions may be directed at cutaneous disease activity, damage, and depression.     

No differences in patient-reported outcomes between medial pivot insert and symmetrical insert in total knee arthroplasty: A randomized analysis

Background

Although total knee arthroplasty (TKA) using a medial pivot insert reportedly improves kinematics compared with a symmetrical insert, improvements in patient-reported outcomes have not yet been reported. The aim of this study was to determine whether insert designs influenced patient-reported outcomes.

Sodium caseinate induces mouse granulopoiesis

Objective and design

Sodium caseinate (CasNa) induces differentiation and M-CSF production in mouse band granulocytes in vitro; however, it is not yet known if this molecule can also induce the proliferation and activation of the granulocyte lineage in vivo. In this work we evaluated the induction in vivo of granulopoiesis and the activation of granulocytes in mice treated with CasNa.

Material or subjects

BALB/c male mice 8–12?weeks old were used.

Treatment

The animals were inoculated intraperitoneally with 1?ml of CasNa (10% in PBS p/v) four times (every 48?h).

Methods

Granulocyte proliferation was evaluated by flow cytometry; activation was evaluated by phagocytic indices. The cytokine was measured using an ELISA assay.

Results

We show that CasNa increased bone marrow granulopoiesis percentage (38.35?±?10.88 vs. 64.94?±?34.14 BrdU+/Gr-1+ cells) and the granulocytes generated presented increased phagocytic indices (0.3?±?0.1 vs. 0.6?±?0.11, p?p?Conclusions CasNa induces granulopoiesis with functional granulocytes, suggesting that this molecule could be an innate immune system activator.     

Effects of Preoperative Short Term Use of Atorvastatin on Endothelial Progenitor Cells after Coronary Surgery: A Randomized, Controlled Trial

Objectives

We investigated the effects of short-term use of atorvastatin on CD34+/VEGF-R2+/CD133+/CD45- endothelial progenitor cell (EPC) count after on-pump coronary artery bypass surgery (CABG).

Methods

Between Feb-2010 and May-2010, we randomly assigned, in a placebo-controlled, double-blind study, 60 consecutive patients who underwent isolated, first-time CABG to receive either 14-day atorvastatin (40 mg/day) or placebo preoperatively. Urgent CABG and recent myocardial infarction were excluded. EPCs were quantified (cells/μl) by flow cytometric phenotyping obtained from venous blood samples collected preoperatively (T₁), 6-hours (T₂), and on the 5th day postoperatively (T₃). Levels of markers of inflammation and serum cardiac troponin I were also measured preoperatively and daily until day-5 after surgery.

Results

There were no differences in baseline risk factors including cholesterol profiles, and EuroSCORES between the groups. The composite primary end-point, favored statin group with higher amount of circulating, early EPC count (cells/μl) at all time points compared with placebo (T₁, 2.30?±?0.02 versus 1.58?±?0.03, p?2, 5.00?±?0.06 versus 2.19?±?0.06, p?3, 3.03?±?0.08 versus 1.78?±?0.02, p?1, 0.8?±?0.1 versus 2.2?±?1.5, p?2, 72.9?±?3.2 versus 96.0?±?3.6, p?3, 4.3?±?1.2 versus 11.4?±?4.1, p?p?=?0.02).

Conclusions

Short-term atorvastatin use increases circulating early EPCs both pre- and post-operatively and is associated with better preservation of sinus rhythm and reduced hsCRP levels. (ClinicalTrials.gov number, NCT01096875)     

Cancer Survival Through Lifestyle Change (CASTLE): a Pilot Study of Weight Loss

Background

Excess weight is a strong predictor of incident breast cancer (BC) and survivorship. A limited number of studies comparing strategies for promoting successful weight loss in women with remitted BC exist.

Purpose

CASTLE was a pilot study comparing the effectiveness/feasibility of in-person and telephonic behavioral-based lifestyle weight loss interventions in BC survivors.

Method

Fifty-two overweight/obese women (BMI?=?25–45 kg/m²) with remitted BC (stages I–IIIa) who recently completed cancer treatment were assigned to either an in-person group (n?=?24) or an individual telephone-based condition (n?=?11). Both interventions focused on increasing physical activity and reducing caloric intake. The phase I intervention lasted 6 months. The in-person condition received 16 group-based sessions, and the telephone condition received intervention calls approximately weekly. Phase II lasted 6 months (e.g., months 6–12), and all participants received monthly intervention calls via telephone.

Results

Participants were predominately Caucasian (80 %) with a mean age of 52.8 (8.0) years and BMI of 31.9 (5.4) kg/m². Mixed models ANOVAs showed significant within group weight loss after 6 months for both the in-person (?3.3 kg?±?4.4, p?=?0.002) and the telephonic (?4.0 kg?±?6.0, p?=?0.01) conditions with no between group differences. During phase II, the in-person group demonstrated significant weight regain (1.3 kg?±?1.7, p?=?0.009).

Conclusion

Our pilot study findings demonstrated that telephone-based behavioral weight loss programs are effective and feasible in BC survivors and that telephonic programs may have advantages in promoting weight loss maintenance.     

In vitro and in vivo safety evaluation of Dipteryx alata Vogel extract

Background

The skin is chronically exposed to endogenous and environmental pro-oxidant agents, leading to the harmful generation of reactive oxygen species. Antioxidant is vital substances which possess the ability to protect the body from damage cause by free radicals induce oxidative stress. Alpinia zerumbet, a traditionally important economic plant in Okinawa, contains several interesting bioactive constituents and possesses health promoting properties. In this regard, we carried out to test the inhibitory effect of crude extracts and isolated compounds from A. zerumbet on antioxidant and skin diseases-related enzymes.

Methods

The antioxidant activities were examined by DPPH, ABTS and PMS-NADH radical scavenging. Collagenase, elastase, hyaluronidase and tyrosinase were designed for enzymatic activities to investigate the inhibitory properties of test samples using a continuous spectrophotometric assay. The inhibitory capacity of test samples was presented at half maximal inhibitory concentration (IC₅₀).

Results

The results showed that aqueous extract of the rhizome was found to have greater inhibitory effects than the others on both of antioxidant and skin diseases-related enzymes. Furthermore, 5,6-dehydrokawain (DK), dihydro-5,6-dehydrokawain (DDK) and 8(17),12-labdadiene-15,16-dial (labdadiene), isolated from rhizome, were tested for antioxidant and enzyme inhibitions. We found that DK showed higher inhibitory activities on DPPH, ABTS and PMS-NADH scavenging (IC₅₀?=?122.14?±?1.40, 110.08?±?3.34 and 127.78?±?4.75???g/ml, respectively). It also had stronger inhibitory activities against collagenase, elastase, hyaluronidase and tyrosinase (IC₅₀?=?24.93?±?0.97, 19.41?±?0.61, 19.48?±?0.24 and 76.67?±?0.50???g/ml, respectively) than DDK and labdadiene.

Conclusion

Our results indicate that the rhizome aqueous extract proved to be the source of bioactive compounds against enzymes responsible for causing skin diseases. Moreover, DK could be used as a potent inhibitor and be further exploited to be used in anti-skin disease formulations.     

Local and systemic pro-inflammatory and anti-inflammatory cytokine patterns in patients with chronic subdural hematoma: a prospective study

Objective and design

Innate immune pro- and anti-inflammatory responses in patients with chronic subdural hematoma (CSDH) were investigated by measuring and comparing the systemic and subdural fluid levels of cytokines.

Materials and method

Cytokine values were analyzed in samples obtained during surgery of 56 adult patients who were operated on for unilateral CSDHs using a Multiplex antibody bead kit.

Results

There were significantly higher levels of the pro-inflammatory IL-2R (p?=?0.004), IL-5 (p?<?0.001), IL-6 (p?<?0.001), and IL-7 (p?<?0.001), and anti-inflammatory mediators IL-10 (p?<?0.001) and IL-13 (p?=?0.002) in CSDH fluid compared with systemic levels. The pro-inflammatory TNF-alpha (p?<?0.001), IL-1beta (p?<?0.001), IL-2 (p?=?0.007) and IL-4 (p?<?0.001) were significantly lower in hematoma fluid compared with systemic levels. The ratios between pro- versus anti-inflammatory cytokines were statistically significant higher in CSDH (7.8) compared with systemic levels (1.3).

Conclusions

The innate immune responses occur both locally at the site of CSDH, as well as systematically in patients with CSDH. The local hyper-inflammatory and low anti-inflammatory responses exist simultaneously. The findings suggest poorly coordinated innate immune responses at the site of CSDH that may lead to propagating of local inflammatory process and basically contribute to formation and progression of CSDH.     

The influence of ice slurry ingestion on maximal voluntary contraction following exercise-induced hyperthermia

The purpose of this study was to determine whether ingestion of a small bolus of ice slurry (1.25?g?kg^?1) could attenuate the reduction in maximal voluntary isometric contraction (MVC) torque output during a 2-min sustained task following exercise-induced hyperthermia. On two separate occasions, 10 males (age: 24?±?3?years, $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ : 49.8?±?4.7?ml?kg^?1?min^?1) ran to exhaustion at their first ventilatory threshold in a hot environment (34.1?±?0.1°C, 49.5?±?3.6% RH). Prior to and after exercise, subjects performed a 2-min sustained MVC of the right elbow flexors in a thermoneutral environment (24.6?±?0.8°C, 37.2?±?4.5% RH). The post exercise MVC was performed immediately following the ingestion of either 1.25?g?kg^?1 of ice slurry (?1°C; ICE) or warm fluid (40°C; CON), in a counterbalanced and randomised order. Run time to exhaustion (42.4?±?9.5 vs. 41.7?±?8.7?min; p?=?0.530), and rectal (39.08?±?0.30 vs. 39.08?±?0.30°C; p?=?0.934) and skin temperatures (35.26?±?0.65 vs. 35.28?±?0.67°C; p?=?0.922) and heart rate (189?±?5 vs. 189?±?6 beats?min^?1; p?=?0.830) at the end of the run were similar between trials. Torque output during the post-exercise 2-min sustained MVC was significantly higher (p?=?0.001) following ICE (30.75?±?16.40?Nm) compared with CON (28.69?±?14.88?Nm). These results suggest that ice slurry ingestion attenuated the effects of exercise-induced hyperthermia on MVC, possibly via internal thermoreceptive and/or temperature-related sensory mechanisms.     

Usefulness of C-reactive protein as a marker of early post-infarct left ventricular systolic dysfunction

Objective

To assess the usefulness of in-hospital measurement of C-reactive protein (CRP) concentration in comparison to well-established risk factors as a marker of post-infarct left ventricular systolic dysfunction (LVSD) at discharge.

Materials and methods

Two hundred and four consecutive patients with ST-segment-elevation myocardial infarction (STEMI) were prospectively enrolled into the study. CRP plasma concentrations were measured before reperfusion, 24?h after admission and at discharge with an ultra-sensitive latex immunoassay.

Results

CRP concentration increased significantly during the first 24?h of hospitalization (2.4?±?1.9 vs. 15.7?±?17.0?mg/L; p?p?p?p?p?Conclusion Measurement of CRP plasma concentration at discharge may be useful as a marker of early LVSD in patients after a first STEMI.     

The effect of sRAGE-Fc fusion protein attenuates inflammation and decreases mortality in a murine cecal ligation and puncture model

Objective

Inhibition of the receptor for advanced glycation end products (RAGE) may attenuate the systemic inflammatory response and ensuing severe sepsis. We report an investigation into the effect of soluble RAGE (sRAGE)-Fc fusion protein in severe sepsis induced by a cecal ligation and puncture (CLP) procedure.

Materials and methods

The experiment was performed using CLP control mice, mice treated with 0.5 or 1.0?μg sRAGE-Fc fusion protein, and sham surgery mice.

Results

Survival benefits over the CLP control group were evident (P?=?0.036) in mice given 1.0?μg sRAGE-Fc fusion protein. In addition, the pulmonary inflammation score in the sRAGE-Fc fusion protein-treated group was significantly lower than that in the CLP control group (P?<?0.05). Lung tissue in the sRAGE-Fc fusion protein-treated group revealed a significant decrease in the expression of inflammatory cytokines. Furthermore, levels of interleukin (IL)-1β and tumor necrosis factor-α were significantly lower in sRAGE-Fc fusion protein treated groups (P?<?0.001). Moreover, IL-6 levels showed a significant difference between CLP control and sRAGE-Fc fusion protein treated groups (P?<?0.01).

Conclusions

sRAGE-Fc fusion protein has beneficial effects in a standard murine model of polymicrobial, intra-abdominal severe sepsis.     

Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome

Introduction

Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control.

Methods

This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-α), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects.

Results

Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P?=?0.017), IL-6 G allele at position ?174 (P?=?0.002), and TNF-α G allele at position ?238 (P?<?0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (?174) and TNF-α GG genotype (?238) in the patient group were also significantly overrepresented (P?<?0.001), while IL-6 CG genotype (?174) and TNF-α GA genotype (?238) were significantly decreased in the patients with IBS (P?<?0.001). The frequencies of IL-6 (?174, nt565) GG haplotype and TNF-α (?308, ?238) GG haplotype were also significantly higher in the patient group (P?<?0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-α GA were significantly decreased in the patients with IBS (P?<?0.001).

Conclusion

IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.     

Self-reported outcomes are associated with knee strength and functional symmetry in individuals who have undergone anterior cruciate ligament reconstruction with hamstring tendon autograft

Background

The aim of this study was to investigate the relationship between self-reported knee outcomes and limb symmetry indices (LSIs) for hip and knee strength, postural control and single-leg hop distance in individuals who had undergone an anterior cruciate ligament (ACL) reconstruction via hamstring tendon autograft (HTG).

The Contralateral Extremity has Also Benefit from the Locally Administered Bone Marrow-Derived Mononuclear Cells and Cord Blood Serum in Diabetic Ischemic Wound Healing

Objective

Impaired wound healing could be a disaster especially in diabetes and amputation is the major risk. The aim of this study was to evaluate the benefit of BMMCs and CBS on wound healing.

Methods

Diabetic rats were underwent bilateral limb ischemia and wounding of skin defects on both extremities. The groups were formed as BMMCs (group A), BMMCs and CBS (group B), only CBS (group C), and phosphate buffer solution (group D) that were injected into wounds on right legs.

Results

The complete recovery of right legs was established as a mean of 21.4?±?1.1 days, 12.9?±?1.5 days, 30.0?±?0.0 days and 38.1?±?1.5 days according to Groups A, B, C, and D (p?<?0.05). The recovery of left legs were calculated as a mean of 27.0?±?0.0 days, 24.0?±?0.0 days, 35.6?±?1.1 days and 37.3?±?1.6 days according to Groups A, B, C and D (p?<?0.05). At the end of the recovery, the HE staining showed that vascularity was increased in groups A and B.

Conclusion

Transplantation of BMMCs and CBS to the ischemic wounds of the diabetic rats accelerate the repair. The recovery was also superior in the same group although the treatment was not applied to the left extremity directly.     

Characterization of Interleukin-33 and Soluble ST2 in Serum and Their Association with Disease Severity in Patients with Chronic Kidney Disease

Introduction

This study aims to test the serum levels of interleukin-33 (IL-33) and soluble ST2 (sST2) in patients with chronic kidney disease (CKD) and to evaluate their association with disease severity.

Methods

Sixty-nine patients with CKD were enrolled, disease severity was assessed, and clinical data were collected. Twelve healthy volunteers served as healthy individuals. Serum IL-33 and sST2 were tested by enzyme-linked immunosorbent assay.

Results

The patients were classified into five categories based on their estimated glomerular filtration rate (eGFR). No difference was found as to the serum concentration of IL-33 between CKD patients and healthy individuals (p?=?0.656), while a higher serum level of sST2 was found in CKD patients (p?=?0.003). The correlation analysis revealed a significant correlation between the serum level of sST2 and disease severity (r?=?0.586; p?p?=?0.001). Serum sST2 correlated with parathyroid hormone (r?=?0.412; p?r?=?0.545; p?r?=??0.494; p?Conclusion An elevated concentration of serum sST2 is found in CKD patients and correlates with disease severity. Serum sST2 may be also associated with parathyroid hormone disorder of CKD. The sST2 may have an important role in the development of CKD or as a marker of disease severity.     

Clinical and Genetic Characterization of Japanese Sporadic Cases of Periodic Fever,Aphthous Stomatitis,Pharyngitis and Adenitis Syndrome from a Single Medical Center in Japan

Purpose

To investigate clinical presentation, genetic background and cytokine profile of Japanese sporadic cases of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome.

Methods

Nine PFAPA syndrome patients were recruited. DNA sequence analysis of auto inflammatory disorder susceptibility genes, MEFV, MVK, NLRP3, and TNFRSF1A, were performed. Serum cytokine levels and monocyte IL-1β levels were measured by ELISA.

Results

The study population consisted of six males and three females (mean age of onset 26.8 months). Febrile episodes lasted 3–6 days with symptom-free intervals ranging from 2 to 12 weeks. Fever was accompanied by pharyngitis (n?=?8), aphthous stomatitis (n?=?4), and cervical adenitis (n?=?5). White blood cells and C-reactive protein were increased during the attack phase. Mean IgD serum levels were 7.32?±?9.51 mg/dl during the attack phase, and were mildly elevated in two patients. Heterozygous MEFV, NLRP3 and TNFRSF1A variants were detected in four, one and three cases, respectively. Serum TNF-α and IL-18 levels were elevated during the attack-free and attack periods compared with controls. Other cytokines, IL-1β, IL-1ra, IL-6, and sTNFR1, were only increased during the attack phase. Oral prednisolone was administered to eight patients and immediately reduced fever. Tonsillectomy performed in five patients induced cessation of fever in four patients. One case with repeated fever attacks after tonsillectomy showed increased monocyte IL-1β production, similar to the other active case with genetic variants of auto inflammatory disorder-associated genes.

Conclusions

Japanese PFAPA syndrome patients may have cytokine regulation dysfunction as a result of genetic variants of auto inflammatory disorder-associated genes.