Hyperamylasemia induced by percutaneous papillary balloon dilatation for symptomatic choledocholithiasis

BACKGROUND/AIMS: We investigated the relationship between percutaneous papillary balloon dilatation (PPBD) and hyperamylasemia after PPBD. METHODOLOGY: We studied the rate of pancreatitis and asymptomatic hyperamylasemia after PPBD for choledocholithiasis in 64 symptomatic patients. Pancreatitis was defined as epigastric pain combined with at least a 3-fold rise in serum amylase at 24 hours after PPBD. Asymptomatic hyperamylasemia was defined as a rise in serum amylase (normal range, 50 to 160 IU/L) without epigastric pain. RESULTS: The stones were successfully pushed out into the duodenum in all patients. Three patients developed post-PPBD pancreatitis, graded moderate in one and mild in two. Serum amylase values were elevated over the normal upper limit in 21 patients, 33%, over 3-fold in 10, 16% over 1000 IU/L in 6, 9%. Asymptomatic hyperamylasemia was observed in 18 patients. The amylase value after PPBD was elevated to more than 160 IU/L in 44% (17/39) of patients 80 years old or under vs. 16% (4/25) of patients older than 80 and in 23% (10/44) of patients with intrahepatic bile duct dilatation on admission vs. 55% (11/20) of patients without it, with a significant difference, respectively (p<0.05). The amylase value after PPBD was elevated to more than 1000 IU/L in 15% (6/39) of patients 80 years old or under vs. 0% (0/25) of patients older than 80 and in 29% (4/14) of patients with bile duct stones having a horizontal diameter of 8mm or smaller and 4% (2/50) of patients with stones larger than 8mm (p < 0.05 and p<0.01, respectively). CONCLUSIONS: We believe that postoperative continuous decompression of the bile duct by PPBD is reliable and that it contributed to the prevention of severe pancreatitis. We conclude that PPBD can be performed more safely in symptomatic patients older than 80 with choledocholithiasis with intrahepatic bile duct dilatation at the time of admission.     

Evolocumab Effects on Lipoproteins,Measured by High-Performance Liquid Chromatography

Aims: Profiling of lipoproteins can predict risk of cardiovascular disease; gel permeation high-performance liquid chromatography (HPLC) improves prediction accuracy by providing detailed data for specific lipoprotein subclasses. This study applied HPLC to examine the effects of evolocumab, which effectively treats hyperlipidemia and mixed dyslipidemia, on lipoprotein subclasses, specifically the number and size of lipoprotein particles.Methods: This post-hoc analysis used patient blood samples from YUKAWA-2, a phase 3 trial evaluating the efficacy of evolocumab in Japanese adult patients with hyperlipidemia or mixed dyslipidemia and at high risk for cardiovascular disease. We used HPLC to assess observed values and percent change from baseline in cholesterol and triglyceride (TG) concentrations, number of particles in lipoprotein subclasses to week 12, and mean observed values and mean percent change from baseline in variables to weeks 10 and 12. HPLC was also compared with conventional methods in assessing low-density lipoprotein (LDL) cholesterol (LDL-C) values.Results: Data for all 404 patients were analyzed. Evolocumab significantly decreased cholesterol and TG concentrations, and total particle count, in very low-density lipoprotein (VLDL) and LDL subclasses. Particle size increased slightly in LDL, high-density lipoprotein (HDL), and VLDL, but data varied widely. At very low L-DLC, HPLC measurements were higher than those from conventional methods.Conclusion: This research used HPLC to assess the effects of evolocumab in 20 lipid subclasses. By lowering lipid content and improving the lipid profile, evolocumab may reduce atherogenicity. This reduction is better quantified by HPLC than by conventional methods in the very low LDL-C range.     

Influence of PD‐L1 cross‐linking on cell death in PD‐L1‐expressing cell lines and bovine lymphocytes

Programmed death‐ligand 1 (PD‐L1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death‐1 (PD‐1). However, the mechanism of PD‐L1‐mediated inhibitory signalling after PD‐L1 cross‐linking by anti‐PD‐L1 monoclonal antibody (mAb) or PD‐1–immunogloblin fusion protein (PD‐1‐Ig) is still unknown, although it may induce cell death of PD‐L1⁺ cells required for regular immune reactions. In this study, PD‐1‐Ig or anti‐PD‐L1 mAb treatment was tested in cell lines that expressed PD‐L1 and bovine lymphocytes to investigate whether the treatment induces immune reactivation or PD‐L1‐mediated cell death. PD‐L1 cross‐linking by PD‐1‐Ig or anti‐PD‐L1 mAb primarily increased the number of dead cells in PD‐L1^high cells, but not in PD‐L1^low cells; these cells were prepared from Cos‐7 cells in which bovine PD‐L1 expression was induced by transfection. The PD‐L1‐mediated cell death also occurred in Cos‐7 and HeLa cells transfected with vectors only encoding the extracellular region of PD‐L1. In bovine lymphocytes, the anti‐PD‐L1 mAb treatment up‐regulated interferon‐γ (IFN‐γ) production, whereas PD‐1‐Ig treatment decreased this cytokine production and cell proliferation. The IFN‐γ production in B‐cell‐depleted peripheral blood mononuclear cells was not reduced by PD‐1‐Ig treatment and the percentages of dead cells in PD‐L1⁺ B cells were increased by PD‐1‐Ig treatment, indicating that PD‐1‐Ig‐induced immunosuppression in bovine lymphocytes could be caused by PD‐L1‐mediated B‐cell death. This study provides novel information for the understanding of signalling through PD‐L1.     

Butyric acid induces apoptosis in both human monocytes and lymphocytes equivalently

Short-chain fatty acids (SCFAs) are metabolites from anaerobic periodontopathic bacteria that induce apoptosis in immune cells such as lymphocytes, monocytes and macrophages. However, it remains unclear if SCFAs from pathogens induce apoptosis in monocytes/macrophages similarly with lymphocytes. This study investigated whether SCFAs-induced apoptosis is equal among the immunoregulatory cells. Cell apoptosis of the employed human cells was evaluated after treatment with culture supernatants from various periodontopathic bacteria or sodium butyrate. Apoptosis and viability were determined by detection of DNA fragmentation and using an MTS assay kit, respectively. Porphyromonas gingivalis and Fusobacterium nucleatum culture filtrates strongly induced apoptosis whereas Prevotella nigrescens and Prevotella intermedia culture filtrates failed to induce apoptosis in the THP-1 and U937 human monocyte and macrophage cell lines. Healthy gingival fibroblasts and oral epithelial cells were resistant to all the culture filtrates. Gas-liquid chromatography detected butyric acid in P. gingivalis (21.0-34.0 mM) and F. nucleatum (36.0 mM) in culture filtrates, whereas, only trace levels were seen in P. nigrescens and P. intermedia. These results suggest that butyric acid produced by periodontopathic bacteria severely damages immunoregulatory cells in a consistent manner and, likewise, could be involved in mediating periodontal chronic inflammation.     

Clinical study on anti-fungal drug activity against clinically isolated strains of oral Candida species

ObjectivesThe present study was undertaken to evaluate the anti-fungal activity of amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), miconazole (MCZ), itraconazole (ITCZ), and micafungin (MCFG) against clinically isolated Candida strains from oral candidiasis (OC) patients and to collect information useful for the treatment of OC.Subjects and methodsThe study includes 116 strains of Candida isolated from patients. The Candida species were identified by polymerase chain reaction. The minimum inhibitory concentration (MIC) of each drug against each Candida species was determined.ResultsOf the 106 participants (30 males and 76 females), 57 had OC, including 42 cases of pseudomembranous OC, 11 cases of erythematous OC, 2 cases of hypertrophic OC, and 2 cases of mixed pseudomembranous/erythematous OC. The Candida species isolated were Candida albicans (93 strains), C. glabrata (19 strains), and C. tropicalis (4 strains). AMPH-B and 5-FC had low MIC values against all species of Candida and a low incidence of resistance development. In some species of Candida, FLCZ and ITCZ showed high MICs, but MCZ had a low MIC value. AMPH-B, MCZ, and ITCZ prescribed to OC patients were effective against OC with respect to alleviation of OC symptoms.ConclusionMIC values of anti-fungal drugs against Candida strains isolated from OC patients were obtained and the 3 anti-fungal drugs given to OC patients were found to be effective against OC in spite of differences in their MIC values and in the number of resistant strains (or strains with a high MIC value).     

Effect of switching from salmeterol/fluticasone to formoterol/ budesonide combinations in patients with uncontrolled asthma

BackgroundCombination therapy with an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) in a single inhaler is the mainstay of asthma management and salmeterol/fluticasone combination (SFC) and fixed-dose formoterol/budesonide combination (FBC) are currently available in Japan; however, there is nothing to choose between the two. The purpose of this study was to clarify the effect of switching from SFC to FBC in patients with asthma not adequately controlled under the former treatment regimen.MethodsThis was a prospective, multicenter, open-label, uncontrolled longitudinal study in 87 adult patients with an Asthma Control Questionnaire, 5-item version (ACQ5) score of greater than 0.75 under treatment with SFC 50/250 μg one inhalation twice daily (bid). SFC was switched to FBC 4.5/160 μg two inhalations bid. Study outcomes included ACQ5 score, peak expiratory flow (PEF), FEV₁, and fractional exhaled nitric oxide (FeNO) at the end of treatment period.ResultsEighty-three patients completed the study. ACQ5 scores improved and exceeded the clinically meaningful difference after 12 weeks of treatment and well-controlled asthma (ACQ5 score ≤ 0.75) was attained in 37 (44.6%) patients. Minimum and maximum PEF and FEV₁ values improved significantly, but not FeNO values, after switching from SFC to FBC.ConclusionsSwitching ICS/LABA combination therapy is a useful option in the management of asthma that is not optimally controlled.     

Characteristics and distribution of complex fractionated atrial electrograms and the dominant frequency during atrial fibrillation: relationship to the response and outcome of circumferential pulmonary vein isolation

Background

Although sites of complex fractionated electrograms (CFAEs) and dominant frequency (DF) are known to be critical for the maintenance of atrial fibrillation (AF), spatial distribution of CFAEs and DF and their impact on the outcome of AF ablation remain unclear.

Methods

We created CFAE and DF maps of the left atrium (LA), right atrium, and pulmonary veins (PVs) with a NavX mapping system and simultaneously calculated the DF values with a Bard LabSystem Pro in 40 patients with AF (nonparoxysmal, n?=?16).

Results

In 19 patients in whom circumferential PV isolation (CPVI) terminated AF, there was a high DF in the PVs (Bard-based DF value, 6.70?±?1.01?Hz), low DF in the LA body (5.94?±?0.75?Hz), and a significant PV-to-LA body DF gradient (0.76?±?0.65?Hz), and the CFAEs were located mainly in the PV antrum. In the 21 patients not responding to CPVI, a high DF was located in both the PVs (7.04?±?0.81?Hz) and LA body (6.75?±?0.81?Hz), and therefore, the PV-to-LA body DF gradient was smaller than that in the CPVI responders (0.29?±?0.52?Hz, P?=?0.0160), and the CFAEs extended to the LA body. The higher DF in the LA body, nonparoxysmal AF, and longer AF duration remained as independent predictors of a post-ablation AF recurrence by using a multivariate analysis.

Conclusions

A higher LA-DF value, smaller PV-to-LA DF gradient, and wider LA-CFAE distribution were noted more often in the nonresponders to CPVI than in the responders. This suggested the presence of an arrhythmogenic substrate in the LA beyond the PVs in patients whose AF persisted after CPVI, which was further associated with post-ablation AF recurrence.