Sarcomatoid variant of urothelial carcinoma of renal pelvis with direct invasion of the pancreas and descending colon.

Introduction: Sarcomatoid variant of urothelial carcinoma infiltrates the perimeter and occurs occasionally. However, there are only few case reports. Case presentation: A left renal tumor was incidentally detected in a 75-year-old woman and protruded outside the kidney, infiltrating the pancreatic tail and spleen. Tumor invasion was observed in the adjacent organs; therefore, the left kidney, pancreatic tail, spleen, and, descending colon were resected. Histopathological examination revealed a sarcomatoid variant of invasive urothelial carcinoma. She received two cycles of gemcitabine and carboplatin combination chemotherapy but succumbed to the disease after 5 months. Conclusion: Sarcomatoid variant of urothelial carcinoma is rare, with aggressive malignancy. The diagnosis was difficult and required surgery. This is the first case of a sarcomatoid variant of urothelial carcinoma with direct invasion into the pancreas and descending colon.

Visit-to-Visit Blood Pressure Variability and Alzheimer's Disease: Links and Risks.

While hypertension has been shown to be a risk factor for vascular dementia, several studies have also demonstrated that hypertension also increases the risk of Alzheimer's disease (AD). Although the relationship between visit-to-visit blood pressure variability (VVV) and cognitive impairment, including AD, have been provided, the mechanisms remain poorly understood. This review paper focuses on the relationship of VVV with AD and summarizes the pathophysiology underlying that relationship, which appears to be mediated by arterial stiffness.

The Insular Cortex and Takotsubo Cardiomyopathy.

Transient left ventricular dysfunction in patients under emotional stress, also known as Takotsubo cardiomyopathy, has been recognized as a distinct clinical entity. Recent studies have supported the concept notion that the cardiovascular system is regulated by cortical modulation. A network consisting of the insular cortex (Ic), anterior cingulate gyrus, and amygdala plays a crucial role in the regulation of the central autonomic nervous system in relation to emotional stress such as anxiety, fear and sadness. Because the Ic is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease. Ic damage has been associated with myocardial injury, increased brain natriuretic peptide, and the incidence of Takotsubo cardiomyopathy. Because Ic damage has been associated with increased sympathetic nervous system activity, Ic damage is suggested to have a pivotal role in the pathophysiology of Takotsubo cardiomyopathy. In this review, we focus on the role of the Ic as a mediator for the cardiovascular system in relation to emotional stress, and we summarizes the current knowledge on the relationships between the Ic and Takotsubo cardiomyopathy.

Intravascular ultrasound for morphological assessment of napkin-ring sign detected on multidetector computed tomography.

BACKGROUND: Although napkin-ring sign (NRS) plaques assessed by multidetector computed tomography (MDCT) is identified as a high-risk feature, the detailed morphological features are still unknown. The purpose of this study was to elucidate the morphological features of the MDCT-assessed NRS using intravascular ultrasound (IVUS). METHODS: We evaluated 204 plaques in 193 patients with non-ST-elevation acute coronary syndrome who were diagnosed using 128-slice MDCT and were assessed using IVUS prior to coronary intervention. Morphology was compared between plaques with and without MDCT-assessed NRS. Severe IVUS-assessed attenuation was defined as an attenuation angle >180°. RESULTS: NRS was detected in 49 lesions. MDCT-assessed plaque attenuation was lower (p<0.0001), and cross-sectional plaque areas at lesion sites, remodeling index, and the prevalence of positive remodeling were greater, in lesions with NRS (p<0.005, p<0.0001, and p<0.0001, respectively). Furthermore, the IVUS-assessed remodeling index and prevalence of severe attenuation and speckled echo appearance were significantly greater in lesions with NRS (p<0.01, p<0.0001, and p<0.0001, respectively). Using multivariate analysis, IVUS-assessed speckled echo appearance was identified as an independent predictor of MDCT-assessed NRS (odds ratio, 3.59; 95% confidence interval, 1.49-8.66; p<0.005). CONCLUSION: MDCT assessment of NRS may be associated with larger heterogeneous necrotic cores and greater positive remodeling.

A case study on Salmonella enterica serovar Typhimurium at a dairy farm associated with massive sparrow death.

BACKGROUND: Salmonella enterica Typhimurium (S. Typhimurium) is the most common cause of bovine salmonellosis in Japan and where it is also cause of salmonellosis in wild birds. In 2008, a postpartum cow at a dairy farm developed diarrhea caused by S. Typhimurium. The herd was extensively surveilled for Salmonella sp. and we characterized bacterial isolates from this and other cows to determine the source of infection. RESULTS: Eight isolates of S. Typhimurium from cattle were identified as phage type DT40 and showed a 100 % similarity by pulsed-field gel electrophoresis and the same or similar multiple-locus variable-number tandem-repeat analysis profiles as those of S. Typhimurium isolated from dead sparrows (Passer montanus) collected at Asahikawa in 2006. S. Typhimurium DT40 was considered to be a major cause of high sparrow mortality in Hokkaido in 2005-2006 and 2008-2009, suggesting that DT40 maintained in sparrows was transmitted to cattle. CONCLUSIONS: S. Typhimurium DT40 may be transmitted from sparrows to dairy cattle.

Visit-to-visit blood pressure variability and classes of antihypertensive agents; associations with artery remodeling and the risk of stroke.

Recent studies have shown that visit-to-visit blood pressure (BP) variability was emerging as an independent risk factor for stroke. Although the mechanism is not fully understood, artery remodeling would be closely associated with the relationship between visit-to-visit BP variability and stroke. In addition, the class of antihypertensive agents is suggested to be an important determinant of visit-to-visit BP variability. This review article summarizes the recent literature on these topics. In the elderly hypertensives, strict BP control using calcium channel blockade would play a crucial role to prevent stroke via reducing the visit-to-visit BP variability.

Usefulness of brain natriuretic peptide for predicting left atrial appendage thrombus in patients with unanticoagulated nonvalvular persistent atrial fibrillation.

BACKGROUND: The CHADS2 scoring system is simple and widely accepted for predicting thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Although congestive heart failure (CHF) is a component of the CHADS2 score, the definition of CHF remains unclear. We previously reported that the presence of CHF was a strong predictor of left atrial appendage (LAA) thrombus. Therefore, the present study aimed to elucidate the relationship between LAA thrombus and the brain natriuretic peptide (BNP) level in patients with unanticoagulated NVAF. METHODS: The study included 524 consecutive patients with NVAF who had undergone transesophageal echocardiography to detect intracardiac thrombus before cardioversion between January 2006 and December 2008, at Hiroshima City Asa Hospital. The exclusion criteria were as follows: paroxysmal atrial fibrillation, unknown BNP levels, prothrombin time international normalized ratio ≥2.0, and hospitalization for systemic thromboembolism. RESULTS: Receiver operating characteristic analysis yielded optimal plasma BNP cut-off levels of 157.1 pg/mL (area under the curve, 0.91; p<0.01) and 251.2 pg/mL (area under the curve, 0.70; p<0.01) for identifying CHF and detecting LAA thrombus, respectively. Multivariate analyses demonstrated that a BNP level >251.2 pg/mL was an independent predictor of LAA thrombus (odds ratio, 3.51; 95% confidence interval, 1.08-10.7; p=0.046). CONCLUSIONS: In patients with unanticoagulated NVAF, a BNP level >251.2 pg/mL may be helpful for predicting the incidence of LAA thrombus and may be used as a surrogate marker of CHF. The BNP level is clinically useful for the risk stratification of systemic thromboembolism in patients with unanticoagulated NVAF.

Do Lower Target Temperatures or Prolonged Cooling Provide Improved Outcomes for Comatose Survivors of Cardiac Arrest Treated With Hypothermia?

BACKGROUND: Optimal protocols for targeted temperature management are still unclear. This study investigated whether lower target temperatures and/or prolonged cooling could provide improved outcomes in comatose survivors of cardiac arrest. METHODS AND RESULTS: This observational study was conducted using the prospectively collected targeted temperature management database in Hiroshima, Japan. Between September 2003 and September 2014, 237 patients treated with TTM after cardiac arrest were enrolled in this study. The target temperatures and durations were assigned by the treating physicians regardless of the patients' conditions. Favorable outcomes were defined as a cerebral performance category scale of 1 or 2 at the 90-day follow-up time point. The rate of favorable outcomes were similar between the patients whose protocols of target temperature were <34°C and ≥34°C (40% versus 35%, P=0.41), cooling durations were <28 and ≥28 hours (33% versus 44%, P=0.11), and rewarming durations were <28 and ≥28 hours (35% versus 41%, P=0.39). However, in patients treated with extracorporeal cardiopulmonary resuscitation, target temperatures <34°C were associated with more favorable outcomes (29% versus 8%, P=0.01). The cooling and rewarming durations >28 hours and target temperatures <34°C were associated with more frequent lethal arrhythmia, pneumonia, and/or bleedings. CONCLUSIONS: Prolonged durations of cooling and rewarming ≥28 hours may not improve outcomes and may increase complications. Further studies are necessary to assess the hypothesis that target temperatures <34°C provide improved outcomes in patients treated with extracorporeal cardiopulmonary resuscitation.

Association of nonculprit plaque characteristics with transient slow flow phenomenon during percutaneous coronary intervention.

BACKGROUND: The slow flow (SF) phenomenon is more prevalent in patients with acute coronary syndrome (ACS), who frequently exhibit vulnerable plaques in remote coronary arteries. We aimed to clarify the impact of nonculprit plaque characteristics on the occurrence of SF using multidetector computed tomography (MDCT). METHODS: The study population comprised 180 consecutive patients with non-ST-segment elevation ACS (NSTE-ACS) who underwent MDCT before intervention. The characteristics of culprit and nonculprit lesions were compared between patients with and without SF. RESULTS: SF was observed in 43 (23.8%) of the 180 patients. The prevalence of positive remodeling (PR), low-attenuation plaque (LAP), and napkin-ring sign (NRS) in culprit lesion was significantly higher in the SF group than in the non-SF group (86.1% vs. 39.4%; p<0.001, 81.4% vs. 18.3%; p<0.001, and 65.1% vs. 16.1%; p<0.001, respectively). The same result was observed for nonculprit lesions (58.1% vs. 14.6%; p<0.001, 45.2% vs. 6.6%; p<0.001, and 14.3% vs. 4.9%; p<0.04, respectively). Multivariate analysis revealed LAP [odds ratio (OR), 12.8; 95% confidence interval (CI), 3.7-54.7; p<0.001], and NRS (OR, 5.1; 95% CI, 1.3-25.3; p=0.03) in culprit lesions and PR (OR, 4.7; 95% CI, 1.1-22.2; p=0.04) in nonculprit lesions were independently associated with SF. CONCLUSIONS: The plaque characteristics of nonculprit lesions are associated with the occurrence of SF during percutaneous coronary intervention. Assessment of plaque characteristics of both culprit and nonculprit lesions using MDCT may be useful for the prediction of SF.

Preparation and evaluation of unpleasant taste-masked pioglitazone orally disintegrating tablets.

This study aimed to evaluate the taste and mouth feel of newly designed orally disintegrating tablets (ODTs) of pioglitazone, which is a typical type 2 diabetes medicine with an unpleasant taste, using a visual analog scale (VAS) analysis. The ODTs were subjected to either of these 2 taste-masking procedures: a physical masking procedure that included coating the inactive core granules with mixture of pioglitazone and Eudragit(®) E PO, followed by mixing the granules with aspartame and other excipients to form the tablet (physical masking ODT); or a gustatory masking procedure that involved blending pioglitazone with both sodium chloride and aspartame, followed by mixing the blend with other excipients to form the tablet (gustatory masking ODT). From the results of the VAS analysis, physical masking could suppress the bitterness but not the astringent; therefore, the overall palatability of the ODT was considered not improved. In contrast, gustatory masking significantly suppressed both the bitterness and astringent, and offered a slight sweetness; therefore, the overall palatability of the ODT was considered improved. In conclusion, VAS is a useful tool to evaluate the taste of ODTs and that gustatory masking can effectively mask the unpleasant taste of pioglitazone ODT.

Presentations of acute coronary syndrome related to coronary lesion morphologies as assessed by intravascular ultrasound and optical coherence tomography.

BACKGROUND: Pathologically, the lesions responsible for acute coronary syndrome (ACS) are ruptures of vulnerable plaques (and occasionally fibrous-cap erosions or calcified nodules) with a superimposed thrombosis. We aimed to clarify the clinical presentations related to the morphologies of coronary lesions of ACS using intravascular ultrasound (IVUS) and optical coherence tomography (OCT). METHODS AND RESULTS: Seventy-five culprit lesions of ACS patients were clearly assessed with IVUS and OCT. Patients were classified into two groups based on the presence or absence of a rupture of a culprit plaque as identified by OCT. Clinical characteristics and lesion morphologies were compared between the two groups. Waist circumference was significantly greater (p<0.02) and prevalence of the metabolic syndrome (MS) higher (p=0.0011) in the rupture group. The prevalence of prodromal angina was higher in patients without plaque ruptures (p<0.0001). Using multivariate analysis, the MS and prodromal angina were independent predictors of rupture of a culprit coronary plaque (odds ratio (OR): 27.30, p<0.003 and OR: 0.04, p=0.0004, respectively). Among the components of the MS, the prevalence of abdominal obesity was a significant independent predictor of rupture of a culprit plaque (OR: 4.24, p<0.02). CONCLUSIONS: There are two presentations related to the coronary lesion morphologies of ACS: we should understand these aspects of ACS.

Should we emergently revascularize occluded coronaries for cardiac arrest?: rapid-response extracorporeal membrane oxygenation and intra-arrest percutaneous coronary intervention.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) and percutaneous coronary intervention (PCI) may be useful in cardiopulmonary resuscitation. However, little is known about the combination of ECMO and intra-arrest PCI. This study investigated the efficacy of rapid-response ECMO and intra-arrest PCI in patients with cardiac arrest complicated by acute coronary syndrome who were unresponsive to conventional cardiopulmonary resuscitation. METHODS AND RESULTS: This multicenter cohort study was conducted with the use of the database of ECMO in Hiroshima City, Japan. Between January 2004 and May 2011, rapid-response ECMO was performed in 86 patients with acute coronary syndrome who were unresponsive to conventional CPR. The median age of the study patients was 63 years, and 81% were male. Emergency coronary angiography was performed in 81 patients (94%), and intra-arrest PCI was performed in 61 patients (71%). The rates of return of spontaneous heartbeat, 30-day survival, and favorable neurological outcomes were 88%, 29%, and 24%, respectively. All of the patients who received intra-arrest PCI achieved return of spontaneous heartbeat. In patients who survived up to day 30, the rate of out-of-hospital cardiac arrest was lower (58% versus 28%; P=0.01), the intra-arrest PCI was higher (88% versus 70%; P=0.04), and the time interval from collapse to the initiation of ECMO was shorter (40 [25-51] versus 54 minutes [34-74 minutes]; P=0.002). CONCLUSIONS: Rapid-response ECMO plus intra-arrest PCI is feasible and associated with improved outcomes in patients who are unresponsive to conventional cardiopulmonary resuscitation. On the basis of these findings, randomized studies of intra-arrest PCI are needed.

Impact of metabolic syndrome on coronary plaque vulnerability in Japanese women with acute coronary syndrome.

BACKGROUND: Previous study has demonstrated that metabolic syndrome (MetS) can predict cardiovascular mortality in men, but the prediction was weak for women. In the present study predictors for multiple complex coronary lesions were investigated to clarify the impact of MetS in Japanese women with acute coronary syndrome (ACS). METHODS AND RESULTS: Subjects were Japanese women with ACS (n=81) who underwent emergency coronary angiography and B-mode carotid ultrasonography. They were divided into 2 groups based on the number of complex plaques. Although the MetS prevalence identified using the Japanese criteria was similar between the 2 groups, using the modified ATP III criteria it was more in patients with multiple coronary lesions than in those with a single coronary lesion (p<0.02). The prevalence of diabetes mellitus (DM) in the multiple group was higher than that in the single group (p<0.008). Significant independent predictors for multiple complex coronary lesions were DM (odds ratio (OR) 4.78, p<0.03) and carotid artery remodeling (OR 8.81, p<0.02). Among the components of MetS, a low level of high-density lipoprotein-cholesterol (<50 mg/dl) was a significant independent predictor (p<0.007). CONCLUSIONS: DM and carotid artery remodeling are useful markers for coronary vulnerability in Japanese women. Gender-specific pathophysiological differences may exist for components of MetS.

Coronary plaque vulnerability in metabolic syndrome: assessment of carotid artery morphology in acute coronary syndrome.

BACKGROUND: The aim of the present study was to investigate the clinical implication of metabolic syndrome and carotid artery morphologies on coronary plaque vulnerability in Japanese men with acute coronary syndrome (ACS). METHODS AND RESULTS: Consecutive ACS Japanese men (n=225) underwent emergent coronary angiography and B-mode ultrasonography within 1 week of the acute coronary event. With a 11.3-MHz linear array transducer, the morphologies of common carotid artery were examined. Common carotid arteries with an intima-media thickness>1.1 mm and interadventitial diameter>8.0 mm were considered to be undergoing carotid artery remodeling. Patients were divided into 2 groups based on the number of complex plaques identified by coronary angiography. Abdominal obesity, low level of high-density lipoprotein and carotid artery remodeling were more often observed in patients with multiple, complex coronary plaques than in patients with a single, complex plaque (p<0.03, p<0.03 and p=0.0001, respectively). Metabolic syndrome and carotid artery remodeling were independent predictors of multiple, complex coronary plaques (odds ratio 1.86, p<0.05; odds ratio 5.96, p<0.0001). CONCLUSION: Metabolic syndrome and carotid artery remodeling might be useful indicators to assess the efficacy of aggressive treatments for secondary prevention of cardiovascular events in ACS Japanese men.

Plain computed tomography for assessment of early coronary microcirculatory damage after revascularization therapy in acute myocardial infarction.

BACKGROUND: Coronary microcirculatory damage is an important factor for the prognosis for acute myocardial infarction (MI) after revascularization. The myocardial enhancement area with contrast media infused during coronary revascularization therapy, detected by computed tomography (CT) just after revascularization, has been reported to correspond to the area of hemorrhagic infarction. The relationship between myocardial contrast enhancement and coronary microcirculatory damage was investigated in the present study. METHODS AND RESULTS: Thirteen patients with acute anterior MI underwent successful coronary revascularization within 6 h of symptom onset were enrolled. The coronary flow velocity pattern was measured using a Doppler guidewire and chest CT assessments were performed immediately after coronary revascularization. The ratio of mean CT number of the highest-enhanced myocardial area and the lumen of the left ventricle was defined as a relative CT number. The relative CT number significantly correlated with coronary diastolic deceleration time (r=-0.78, p<0.002) and coronary diastolic deceleration rate (r=0.74, p<0.04). It also correlated with peak myocardial enzyme release in plasma. CONCLUSION: Myocardial contrast enhancement detected using plain CT just after coronary reperfusion therapy implies coronary microcirculatory damage in acute MI. The relative CT number is useful in evaluating the impaired coronary microcirculatory state.

Formulation study for lansoprazole fast-disintegrating tablet. III. Design of rapidly disintegrating tablets.

Lansoprazole fast-disintegrating tablets (LFDT) are a patient-friendly formulation that rapidly disintegrates in the mouth. LFDT consist of enteric-coated microgranules (mean particle size, approximately 300 microm) and inactive granules. In the design of the inactive granules, mannitol was used as a basic excipient. Microcrystalline cellulose, low-substituted hydroxypropyl cellulose (L-HPC), and crospovidone were used as binders and disintegrants. A new grade of L-HPC (L-HPC-33), with a hydroxypropoxy group content of 5.0-6.9%, was developed and it has no rough texture due to a decrease in water absorption. It was clarified that L-HPC-33 could be useful as a binder and disintegrant in rapidly disintegrating tablets. LFDT contain enteric-coated microgranules in tablet form. The enteric-coated microgranule content in LFDT affect qualities such as tensile strength, disintegration time in the mouth, and dissolution behavior in the acid stage and in the buffer stage of LFDT. The 47.4% content of the enteric-coated microgranules was selected to give sufficient tensile strength (not less than 30 N/cm(2)), rapid disintegration time in the mouth (not more than 30 s), and dissolution behavior in the acid stage and buffer stage similar to current lansoprazole capsules. Compression force affected the tensile strength and the disintegration time in the mouth, but did not affect the dissolution behavior in the acid and buffer stages.

Formulation study for lansoprazole fast-disintegrating tablet. I. Effect of compression on dissolution behavior.

Lansoprazole fast-disintegrating tablet (LFDT) is a new patient-friendly formulation of lansoprazole. Since lansoprazole is an antiulcer agent and is unstable under acidic conditions, we have developed LFDT as an orally disintegrating tablet containing enteric-coated microgranules. The effect of compression on dissolution behavior was investigated, as compression affected cleavage and crushing of the enteric layer. To decrease cleavage and crushing of the enteric layer, the effects of the combined ratio of methacrylic acid copolymer dispersion to ethyl acrylate-methyl methacrylate copolymer dispersion and the concentration of triethyl citrate on the dissolution in the acid stage and the dissolution in the buffer stage were evaluated. By adjusting the ratio of methacrylic acid copolymer dispersion to ethyl acrylate-methyl methacrylate copolymer dispersion to 9 : 1 and adding a 20% triethyl citrate concentration, sufficient flexibility of the enteric layer and sufficient stability against compression forces were achieved. Agglomeration of enteric-coated microgranules during the coating process was decreased at the optimized concentration of triethyl citrate and glyceryl monostearate. We compared the absorption properties of LFDT and lansoprazole capsules in dogs. The absorption profiles of LFDT were similar to those of lansoprazole capsules.