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.     

Comparison of the psychosocial quality of life in hemodialysis patients between the elderly and non‐elderly using a visual analogue scale: The importance of appetite and depressive mood

Aim: The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities. Methods: We examined the psychosocial status of 211 HD patients (72 elderly and 139 non‐elderly) and compared the difference between elderly and non‐elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3‐year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self‐evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)‐15. Results: There was no difference in VAS scores between elderly and non‐elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non‐elderly. VAS scores for mood correlated with GDS‐15 in HD patients. Conclusions: More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non‐elderly. Geriatr Gerontol Int 2012; 12: 65–71.     

Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease

Aim: Recent studies have shown that some antihypertensive medications are associated with a significant reduction in the incidence of Alzheimer's disease (AD). However, it remains uncertain whether antihypertensive drugs may have a preventive effect on cognitive decline in patients with AD. We investigated the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator‐activated receptor γ‐stimulating activity, on cognition and regional cerebral blood flow (rCBF) in elderly hypertensive patients with AD. Methods: A total of 20 patients with probable AD and essential hypertension were randomly assigned to the telmisartan group (n = 10, 40–80 mg daily) or the amlodipine group (n = 10, 5–10 mg daily) for 6 months. Results: The groups had a similar significant reduction in systolic and diastolic blood pressure after treatment. The telmisartan group did not show any changes in cognitive function test scores, while the amlodipine group showed significantly higher scores on the AD Assessment Scale‐Cognitive Subscale (Japanese version). Analysis of covariance to analyze treatment effect revealed that the telmisartan group showed increased rCBF in the right supramarginal gyrus, superior parietal lobule, cuneus, and lingual gyrus compared with the amlodipine group, while the amlodipine group showed increased rCBF only in the right cingulate gyrus compared with the telmisartan group at 6 months. Conclusion: These findings suggest that telmisartan may have additional benefits and be useful for the treatment of elderly hypertensive patients with AD. Geriatr Gerontol Int 2012; 12: 207–214.     

Mesenteric ischemia in acute aortic dissection

Mesenteric ischemia complicated by acute aortic dissection (AAD) is uncommon, but serious, as there is no established treatment strategy and it can progress rapidly to multi-organ failure. Diagnosing mesenteric ischemia before necrotic change is difficult, not only for primary care physicians, but even for gastrointestinal or cardiovascular surgeons as it can occur at any time during surgery. Thus, measures need to be in place at the bedside to enable us to obtain information on visceral perfusion. It is often difficult to decide which of laparotomy or aortic repair should be performed first, especially when there is associated shock or malperfusion of other vital organs. The standard surgical procedures for mesenteric ischemia are prompt revascularization of the mesenteric artery and, if needed, resection of necrotic intestine. However, the development of endovascular treatment and the introduction of hybrid ORs have improved the treatment strategies for mesenteric ischemia. This article reviews the issues of “diagnosis” in relation to the mechanism of mesenteric ischemia, and discusses the current “treatment strategies”.     

Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: confirmation of the correlations with histologic subtypes and gene mutations

Although adenocarcinomas of the lung are associated with epidermal growth factor receptor (EGFR) gene mutations and sensitivity to EGFR tyrosine kinase inhibitors, it remains unclear whether bronchioloalveolar carcinoma (BAC) components and/or subtypes affect these associations. We aimed to clarify correlations between EGFR gene mutations and BAC components and to establish the histologic features as reliable predictors for the mutations. We examined 141 non-small cell lung cancers (NSCLCs), including 118 adenocarcinomas, for mutations in exons 19 and 21 of the EGFR gene together with mutations in codon 12 of the K-ras gene using loop-hybrid mobility shift assays, a highly sensitive polymerase chain reaction-based method. Adenocarcinomas were subdivided into subtypes with a nonmucinous or mucinous BAC component and those without BAC components. In NSCLCs, EGFR mutations were detected in 75 cases (53.2%) and were significantly associated with adenocarcinoma, female sex, and never smoking. Among adenocarcinomas, nonmucinous and mucinous BAC components were significantly associated with EGFR and K-ras gene mutations, respectively. Because EGFR mutations were detected even in most pure nonmucinous BACs, ie, lung adenocarcinoma in situ, EGFR mutation is considered a critical event in the pathogenesis of nonmucinous BAC tumors.     

Effects of chlorogenic acid on carbachol-induced contraction of mouse urinary bladder

Chlorogenic acid (CGA) is a polyphenol found in coffee and medicinal herbs such as Lonicera japonica. In this study, the effect of CGA-induced relaxation on carbachol (CCh)-induced contraction of mouse urinary bladder was investigated. CGA (30–300 μg/ml) inhibited CCh- or U46619-induced contraction in a concentration-dependent manner. SQ22536 (adenylyl cyclase inhibitor) recovered CGA-induced relaxation of CCh-induced contraction; however, ODQ (guanylyl cyclase inhibitor) did not have the same effect. In addition, 3-isobutyl-1-methylxanthine (IBMX) enhanced CGA-induced relaxation; however, forskolin or sodium nitroprusside did not have the same effect. Moreover, Ro 20–1724, a selective phosphodiesterase (PDE) 4 inhibitor, enhanced CGA-induced relaxation, but vardenafil, a selective PDE5 inhibitor, did not have the same effect. In the presence of CCh, CGA increased cyclic adenosine monophosphate (cAMP) level, whereas SQ22536 inhibited the increase of cAMP levels. Moreover, higher cAMP levels were obtained with CGA plus IBMX treatment than the total cAMP levels obtained with separate CGA and IBMX treatments. In conclusion, these results suggest that CGA inhibited CCh-induced contraction of mouse urinary bladder by partly increasing cAMP levels via adenylyl cyclase activation.     

ASO Visual Abstract: A Prospective Multicenter Interventional Study of Surgical Resection for Liver Metastasis from Gastric Cancer: R0 Resection Rate and Operative Morbidity and Mortality

Annals of Surgical Oncology -     

Fibrotic changes in the infrapatellar fat pad induce new vessel formation and sensory nerve fiber endings that associate prolonged pain

The infrapatellar fat pad (IFP) contains nerve fiber endings and is considered to play an important role in the perception of knee pain. However, it is unclear whether and to what degree prolonged pain influences the nociceptive role of the IFP. To answer this question, we established a novel rat model of knee pain in which inflammation is restricted to the IFP. Rats received a single intra-IFP injection of monoiodoacetic acid (MIA) (0.2 mg/10 µL or 1.0 mg/10 µL) in the left knee and a phosphate-buffered saline (10 µL) injection in the right knee as a control. Pain-avoidance behavior and histological changes of the knee joint were measured at multiple time points up to 28 days after MIA injection. Histological analysis showed a transient inflammatory response in the IFP body in the 0.2-mg model, whereas prolonged inflammation followed by fibrotic changes was observed in the 1.0-mg model. Subtle histological alterations were observed in the articular cartilage and IFP surface regardless of the dose. The pain-avoidance behavior test indicated the development of prolonged knee pain throughout the experimental period in the 1.0-mg group. Histological assessments showed a significant increase in calcitonin gene-related peptide (CGRP)-positive nerve fiber endings inside IFPs with fibrosis in newly vascularized surrounding regions. These data suggest that irreversible fibrotic changes in the IFP induce the formation of new vessels and CGRP-positive nerve fiber endings that associate prolonged pain in the joint.