Relation of inflammatory cytokines to atrial fibrillation after off-pump coronary artery bypass grafting.

OBJECTIVE: It has been observed that a systemic inflammatory response after on-pump coronary artery bypass grafting (CABG) participates in the pathogenesis of postoperative atrial fibrillation (AF). In patients undergoing off-pump CABG, it is plausible that inflammation is associated with the development of postoperative AF. The present study examined relation of proinflammatory cytokines, which play an important role in the upstream of inflammatory cascade, to the development of AF after off-pump CABG. METHODS: The present study included 39 patients undergoing off-pump CABG. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8, were measured by enzyme-linked immunosorbent assay, on anesthetic induction, after sternotomy before anastomoses, at the completion of anastomoses, 3 and 6h thereafter, and on postoperative days (POD) 1-4. C-reactive protein (CRP) was also measured by turbidimetric immunoassay, preoperatively, and on POD 1, 2, 3, 6, 9, and 13. RESULTS: Eleven patients (28%) developed postoperative AF. Patients with postoperative AF were older (70+/-6.4 years vs 60+/-8.8 years, P=0.001); however, there was no difference in other pre- and perioperative variables. TNF-alpha level did not change during the study period. However, IL-8 and CRP levels significantly increased after the surgery, although there was no significant difference between the two groups. IL-6 level also increased after the surgery with its peak at 6h after the completion of anastomoses. IL-6 levels of 3 and 6h after anastomoses were significantly higher in patients with postoperative AF (360+/-143 pg/ml vs 230+/-94 pg/ml, P=0.0047, 435+/-175 pg/ml vs 247+/-102 pg/ml, P=0.0005, respectively). Logistic regression analysis indicated that the highest quartile of IL-6 level immediately after the surgery (odds ratio 7.63; 95% CI, 1.06-54.9; P=0.04) and age (odds ratio 1.18; 95% CI, 1.01-1.39; P=0.04) independently predict postoperative AF. Furthermore, the maximum level of IL-6 immediately after the surgery significantly correlated to age and intraoperative blood loss (r=0.04, P=0.01, and r=0.47, P=0.04, respectively). CONCLUSIONS: Advanced age was a major risk factor for postoperative AF. Furthermore, inflammatory response induced by surgical trauma was also associated with the development of AF after off-pump CABG.     

Regional distinctions in cortical bone mineral density measured by pQCT can predict alterations in material property at the tibial diaphysis of the Cynomolgus monkey

We examined whether regional differences in cortical bone mineral density (Ct.BMD) measured by peripheral quantitative computed tomography is related to the heterogeneity of bone tissue and whether regional Ct.BMD is a better indicator of changes in bone material properties. Bilateral tibiae were obtained from 17 female adult Cynomolgus monkeys (Macaca fascicularis; mean age 16.8 years). After determining that Ct.BMD was similar between the right and left tibiae, the left tibiae were used for bone histomorphometry and the right for a three-point bending test. The Ct.BMD in the posterior quadrant was significantly higher than that in the anterior quadrant. In the bone histomorphometric analysis, all parameters (i.e., average osteonal area, average osteonal bone area, osteon population density, percent osteonal area [%On.Ar], percent osteonal bone area [%On.B.Ar], percent osteonal area of initial remodeling [%Il.On.Ar], percent osteonal area of secondary remodeling [%Sd.On.Ar], porosity, and percent osteoid area in the posterior region) were significantly lower than those in the anterior region. The results indicated that in the same cross-section, bone tissue structure was heterogeneous. Both total- and posterior-Ct.BMD were positively correlated with breaking stress and negatively correlated with toughness, whereas anterior-Ct.BMD was positively correlated with elastic modulus. Backward stepwise multiple regression analyses indicated that posterior-Ct.BMD and total-Ct.BMD were the best variables for predicting breaking stress and toughness, respectively, when age is taken into account. The %On.Ar, %On.B.Ar, and %Il.On.Ar in the posterior region were negatively correlated with elastic modulus. The %On.Ar, %On.B.Ar, and %Sd.On.Ar in the posterior region were positively correlated with toughness. These findings indicated that regional Ct.BMD measurement is useful to assess changes in the material properties of bone associated with the degree of mineralization. In particular, anterior-, posterior-, and total-Ct.BMD can be used separately to predict changes in the material properties of the tibial diaphysis.     

Results of orbital preservation for advanced malignant maxillary sinus tumors

OBJECTIVE: The purpose of the study was to examine the oncological and functional outcomes of multimodality therapy for patients with advanced malignant maxillary sinus tumors that invaded the orbit. STUDY DESIGN: Retrospective study. METHODS: The medical records of 26 patients with orbital invasion were retrospectively analyzed. The patient group consisted of 16 men and 10 women, with a median age of 58 years. The mean follow-up period was 73 months. The most common disease was squamous cell carcinoma. Seven patients had nodal disease. All patients underwent simultaneous combined therapy consisting of conservative surgery through a sublabial incision, radiotherapy, and regional chemotherapy. Patients with nodal disease were treated with either irradiation or selective neck dissection. RESULTS: The 5- and 10-year overall survival rates were 68% and 51%, respectively. The 5- and 10-year local control rates were 66% and 51%, respectively. Overall survival rates and local control rates were significantly worse in patients with disease other than squamous cell carcinoma. Local control rates were significantly worse in patients with orbital apex disease than in patients without orbital apex disease. All 26 patients, despite orbital involvement, retained their orbital contents. Nineteen of these patients demonstrated adequate ocular function. CONCLUSIONS: Combined therapy with conservative surgery, radiotherapy, and regional chemotherapy is an effective method for local control and preservation of ocular function. However, performing orbital conservation procedure in patients with disease other than squamous cell carcinoma and with orbital apex disease must be considered carefully.     

A novel mutation of keratin 9 gene (R162P) in a Japanese family with epidermolytic palmoplantar keratoderma

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited skin disorder characterized by hyperkeratosis of the skin over the palms and soles. Mutations in keratin 9 gene (KRT9) have been demonstrated in EPPK. In this study, we screened a Japanese family with EPPK for KRT9 mutation by polymerase chain reaction amplification of genomic sequences, followed by heteroduplex analysis and direct nucleotide sequencing. The mutation consisted of a G-to-C transversion at codon 162 in exon 1, which was located in the hot spot of the mutations that have been reported previously (R162Q and R162W). However, the amino acid substitution was proline for arginine (R162P) in the 1A rod domain, the highly conserved helix initiation motif of keratin 9. Our result illustrates the repertoire of KRT9 mutation underlying the occurrence of EPPK in a Japanese family and is an important contribution to the investigation of the genotype/phenotype correlation.     

Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated acute phase atopic dermatitis by inducing regulatory T cells

Increase in the number of patients with atopic dermatitis (AD) has been recently reported. T helper (Th) cells that infiltrate AD skin lesions are Th2-type dominant; reduced exposure to environmental Th1-cytokine-inducing microbes is believed to contribute to the increased number of AD patients. Regulatory type immune responses have been also associated with the occurrence of AD. It has been reported that antigen 85B (Ag85B) purified from mycobacteria is a potent inducer of Th1-type immune response in mice as well as in humans. In this study, we have examined the effect of plasmid DNA encoding Ag85B derived from Mycobacterium kansasii on AD skin lesions induced by oxazolone (OX) application. Th2-cytokine mediated mouse AD model with immediate type response followed by a late phase reaction was developed by repeated applications of low-dose OX to sensitized mice. Mice were immunized with plasmid DNA encoding cDNA of Ag85B before OX sensitization or during repeated elicitation phase. Both therapies were associated with significant suppression of immediate type response, clinical appearance, dermal cell infiltration, reduced IL-4 production, and augmented IFN-gamma mRNA expression compared to placebo-treated mice. Additionally, increased number of Foxp3(+) regulatory T cells were observed in the skin sections in Ag85B treated mice. The results of this study suggest that Ag85B DNA vaccine is a potential therapy for Th2 type dermatitis.     

Segmental pulmonary vein antrum isolation using the "large-size" lasso catheter in patients with atrial fibrillation.

BACKGROUND: The limited efficacy and complications of segmental ostial pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have been discussed so, in the present study the feasibility and efficiency of performing segmental pulmonary vein (PV) antrum isolation to treat AF were assessed. METHODS AND RESULTS: A total of 187 patients with drug-refractory AF (paroxysmal 120, persistent 67) underwent segmental PVI guided by circumferential 20-electrode catheters (Lasso). Radiofrequency (RF) current was delivered either at the ostium using a regular Lasso (15-20 mm in diameter, 70 patients: Group 1) or at the antrum using a larger Lasso (25-30 mm in diameter, 117 patients: Group 2). A significantly wider region had to be ablated, with a longer RF application time, to isolate all 4 PVs in Group 2 patients than in Group 1 patients. Although the rate of recurrence of AF after the initial session was equal in both groups, a significantly greater number of patients were free from AF after a mean of 1.4 procedures in Group 2 than in Group 1 (93% vs 76% for paroxysmal AF, 78% vs 48% for persistent AF). CONCLUSIONS: Segmental antral PVI using large-sized Lasso catheters was found to be more effective and safer than ostial PVI for the treatment of AF.     

Molecular diagnosis and characterization of a culture-negative mycotic aneurysm due to ST54 Haemophilus influenzae type b with PBP 3 alterations

Mycotic aneurysm is a rare but life-threatening disease that warrants an integrated therapeutic approach involving surgical intervention and prolonged antibiotic use. However, the causative organisms are often unidentified because antibiotics started empirically render blood and tissue cultures negative. Molecular diagnosis has been reported to be useful in such culture-negative cases. We report a case of a culture-negative mycotic aortic aneurysm due to Haemophilus influenzae, diagnosed by direct 16S rRNA polymerase chain reaction (PCR) and sequencing of the resected aneurysm tissue. PCR for serotype revealed type b, and PCR and sequencing of the ftsI gene revealed alterations in penicillin-binding protein 3, suggesting resistance to ampicillin. Multilocus sequence typing demonstrated that the isolate belonged to sequence type 54.