The three layered structure of orbicularis oris and buccinator complex with partial connection at the modiolus and partial direct continuation.

PURPOSE: This study aimed to clarify the structural arrangement of the orbicularis oris (OOr), the buccinator, and the other perioral muscles around the modiolus. METHODS: The perioral muscles in seventeen cadavers fixed with formalin were dissected in situ and/or in isolated muscle specimens, and their layers were reconstructed schematically upon pantomographic view of the skeleton to evaluate their actions. RESULTS: The buccinator was composed of three parts including upper and lower oblique parts in its superficial layer and a middle transverse part in its deep layer. The superior and inferior OOr were composed of an inner marginal part (IM) and an outer labial part (OL) in each. The perioral muscles as a whole were arranged in three layers. The first layer consisted of the depressor anguli oris and the OL of superior OOr connected at the modiolus in a vertical direction. The second layer consisted of the upper and inner oblique part of buccinator and a part of the OL of inferior OOr connected at the modiolus in a horizontal direction. The third layer contained the middle transverse part of buccinator continuous with the IM of both OOr and a part of the OL of inferior OOr without connection to the modiolus. CONCLUSIONS: The different arrangement of the three layers of perioral muscles around the modiolus could serve as a good basis to predict the actions of the individual perioral muscles on the movement of lips in open/close of the oral fissure and widening/narrowing of the lip width.

Unique morphological architecture of the hamstring muscles and its functional relevance revealed by analysis of isolated muscle specimens and quantification of structural parameters.

The structural and functional differences of individual hamstrings have not been sufficiently evaluated. This study aimed to clarify the morphological architecture of the hamstrings including the superficial tendons in detail using isolated muscle specimens, together with quantification of structural parameters of the muscle. Sixteen lower limbs of human cadavers were used in this study. The semimembranosus (SM), semitendinosus (ST), biceps femoris long head (BFlh), and biceps femoris short head (BFsh) were dissected from cadavers to prepare isolated muscle specimens. Structural parameters, including muscle volume, muscle length, fiber length, sarcomere length, pennation angle, and physiological cross-sectional area (PCSA) were measured. In addition, the proximal and distal attachment areas of the muscle fibers were measured, and the proximal/distal area ratio was calculated. The SM, ST, and BFlh were spindle-shaped with the superficial origin and insertion tendons on the muscle surface, and the BFsh was quadrate with direct attachment to the skeleton and BFlh tendon. The muscle architecture was pennate in the four muscles. The four hamstrings possessed either of two types of structural parameters, one with shorter fiber length and larger PCSA, as in the SM and BFlh, and the other with longer fiber length and smaller PCSA, as in the ST and BFsh. Sarcomere length was unique in each of the four hamstrings, and thus the fiber length was suitably normalized using the average sarcomere length for each, instead of uniform length of 2.7 µm. The proximal/distal area ratio was even in the SM, large in the ST, and small in the BFsh and BFlh. This study clarified that the superficial origin and insertion tendons are critical determinants of the unique internal structure and structural parameters representing the functional properties of the hamstring muscles.

Anatomical study of the soleus: Application to improved imaging diagnoses.

INTRODUCTION: Strains of the soleus are widely found both in amateur and professional athletes. For their accurate regional diagnoses, understanding the anatomy of the spatial relationship between muscular fibers and tendinous structures is important because their interfaces are susceptible sites to muscle strains. Therefore, this study evaluated the precise architecture of the soleus. MATERIALS AND METHODS: We evaluated the precise anatomical architecture of the soleus in 87 formaldehyde-fixed soleus muscles. To calculate mean relative physiological cross-sectional area of each muscular fiber compartment, we measured the fiber length, volume, and pennation angle in isolated compartments. RESULTS: The posterior soleus surface was covered by a broad aponeurotic posterior insertion tendon (PIT), which continued inferiorly to the insertion tendon. The anterior surface had three aponeurotic origin tendons, lateral origin tendon (LOT), medial origin tendon (MOT), and tendinous arch, which were arranged along the soleus margins. The anterior bipennate muscle portion (ABP), surrounded by the three origin structures, terminated as the sagittal insertion tendon (SIT), which continued inferiorly to PIT. The posterior main muscle portion behind LOT and MOT was separated into lateral and medial portions by the SIT. The soleus thus possessed a broad musculotendinous junction. Furthermore, ABP exhibited wide structural diversity in shape and size: in extreme cases, it was duplicated or absent. CONCLUSION: Systematic anatomical descriptions of the soleus will be useful for accurate regional diagnosis of its strains with magnetic resonance imaging and ultrasonography.

Relationship between the Induced Iron Overload Model and Hepatic Erythropoiesis in Xenopus laevis.

Iron is an essential element for hemoglobin synthesis during erythropoiesis. Iron overload, in contrast, adversely affects erythropoiesis and causes organ dysfunction. Research using various animal models may help to elucidate pathophysiological mechanisms induced by excess iron. In the present study, we evaluated the relationship between iron metabolism and erythropoietic activity in the African clawed frog, Xenopus laevis. In X. laevis, both erythropoiesis and iron metabolism occur in the liver. First, we developed a method to quantify iron levels in the liver and plasma using 2-nitroso-5-[N-n-propyl-N-(3-sulfopropyl) amino] phenol (Nitroso-PSAP). We then measured iron levels and analyzed hematopoietic parameters in frogs that were orally administered sodium ferrous citrate (SFC). The hepatic iron level increased in the SFC group, but the number of erythrocytes, hematocrit, and hemoglobin concentration did not change, suggesting that the regulation of the production and release of mature erythrocytes in the liver was not directly affected by dietary iron. At four days after administration of 2 mg/kg SFC, the number of immature erythrocytes decreased in the liver. Interestingly, atypical blood cells with hyper-segmented nuclei were observed, identified by acridine orange cell staining; these atypical blood cells were hardly detectable under the steady state. Compared with previously reported results in mice, the increase in the hepatic iron levels was small, but our results indicate that SFC affects hematopoietic activity. These results establish a novel model for iron metabolism and provide new insights into the relationship between iron metabolism and erythropoiesis in vertebrates.

Anatomic characterization of the femoral nutrient artery: Application to fracture and surgery of the femur.

The localization of nutrient foramina and direction of nutrient canals have been studied. However, information about the origin and extraosseous course of nutrient arteries is lacking in some types of long tubular and irregular bones. Thus, we aimed to reexamine the origin and course of the femoral nutrient artery (FNA) through cadaveric dissection to clarify its anatomic characteristics. Sixty thighs were collected from 57 cadavers. To fix the cadavers and visualize the small arterial branches, 10% formalin was injected from the femoral artery, followed by an injection of acrylic ink. The arterial tree in the posterior part of the thigh was recorded by line drawings. The femur received single or double FNAs via the femoral nutrient foramina, which were on and along the linea aspera. In cases with single FNA (41 of the 60 thighs), it typically arose from the four parts of the profunda femoris system: profunda femoris artery between the origins of the third and fourth perforating arteries; second perforating artery; third perforating artery; and terminal branch. In cases with double FNAs (remaining 19 thighs), the superior FNA typically arose from the second perforating artery, and the inferior FNA arose from the terminal branch of the profunda femoris artery and popliteal system. FNAs are described as branches of the perforating arteries in Terminologia Anatomica and anatomy textbooks. However, we found that FNAs also frequently arose from the profunda femoris artery and popliteal system, in addition to the perforating arteries. Clin. Anat. 33:479-487, 2020. © 2019 Wiley Periodicals, Inc.

Clinical and Prognostic Values of ALBI Score in Patients With Acute Heart Failure.

BACKGROUND: Although liver dysfunction is one of the common complications in patients with acute heart failure (AHF), no integrated marker has been defined. The albumin-bilirubin (ALBI) score has recently been proposed as a novel, clinically-applicable scoring system for liver dysfunction. We investigated the utility of the ALBI score in patients with AHF compared to that for a preexisting liver dysfunction score, the Model of End-Stage Liver Disease Excluding prothrombin time (MELD XI) score. METHODS: We evaluated ALBI and MELD XI scores in 1,190 AHF patients enrolled in the prospective, multicentre Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure study. The associations between the two scores and the clinical profile and prognostic predictive ability for 1-year mortality were evaluated. RESULTS: The mean MELD XI and ALBI scores were 13.4±4.8 and -2.25±0.48, respectively. A higher ALBI score, but not higher MELD XI score, was associated with findings of fluid overload. After adjusting for pre-existing prognostic factors, the ALBI score (HR 2.11, 95% CI: 1.60-2.79, p<0.001), but not the MELD XI score (HR 1.02, 95% CI: 0.99-1.06, p=0.242), was associated with 1-year mortality. Likewise, area under the receiver-operator-characteristic curves for 1-year mortality significantly increased when the ALBI score (0.71 vs. 0.74, p=0.020), but not the MELD XI score (0.71 vs. 0.72, p=0.448), was added to the pre-existing risk factors. CONCLUSIONS: The ALBI score is potentially a suitable liver dysfunction marker that incorporates information on fluid overload and prognosis in patients with AHF. These results provide new insights into heart-liver interactions in AHF patients.

The influence of trunk muscle strength on walking velocity in elderly people with sarcopenia.

[Purpose] Sarcopenia increases the risk of falls and fractures. However, its relationship with walking, which is the generation mechanism of falls, has not been clarified. The purpose of this study was to clarify the trunk muscle strength and the characteristics of walking, in elderly people with sarcopenia. [Participants and Methods] The participants were 40 elderly people aged 65 years and over. The participants were able to walk without assistance and were attending outpatient rehabilitation or community day-care centers. The assessment and measurement items included: the presence or absence of sarcopenia (using the diagnostic criteria of the Asian Working Group for Sarcopenia), lower limb and trunk muscle strength, and characteristics of walking. The participants were divided into two groups depending on the presence or absence of sarcopenia, and a comparison was made between the two groups. [Results] The participants in the sarcopenia group had significantly lower trunk extension muscle strength as compared to the participants in the non-sarcopenia group. In addition, the hip joint maximum flexion moment, ankle joint maximum plantar flexion moment, and walking velocity of participants in the sarcopenia group were significantly lower than those in the non-sarcopenia group. [Conclusion] This study revealed that weakness of the trunk muscle strength causes a decrease in walking velocity in elderly people with sarcopenia.

Specialty-Related Differences in the Acute-Phase Treatment and Prognosis in Patients With Acute Heart Failure　- Insights From REALITY-AHF.

BACKGROUND: The aim of this study was to assess specialty-related differences in the treatment for patients with acute heart failure (AHF) in the acute phase and subsequent prognostic differences. Methods and Results: We analyzed hospitalizations for AHF in REALITY-AHF, a multicenter prospective registry focused on very early presentation and treatment in patients with AHF. All patients were classified according to the medical specialty of the physicians responsible for contributed most to decisions regarding the initial diagnosis and treatment after the emergency department (ED) arrival. Patients initially managed by emergency physicians (n=614) or cardiologists (n=911) were analyzed. After propensity-score matching, vasodilators were used less often by emergency physicians than by cardiologists at 90 min after ED arrival (29.8% vs. 46.1%, P<0.001); this difference was also observed at 6, 24, and 48 h. Cardiologists administered furosemide earlier than emergency physicians (67 vs. 102 min, P<0.001). However, the use of inotropes, noninvasive ventilation, and endotracheal intubation were similar between groups. In-hospital mortality did not differ between patients managed by emergency physicians and those managed by cardiologists (4.1% vs. 3.8%, odds ratio 1.12; 95% confidence interval 0.58-2.14). CONCLUSIONS: Despite differences in initial management, no prognostic difference was observed between emergency physicians and cardiologists who performed the initial management of patients with AHF.

Tissue Distribution and Elimination of Isavuconazole following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats.

Quantitative whole-body autoradiography was used to assess the distribution and tissue penetration of isavuconazole in rats following single and repeated oral-dose administration of radiolabeled isavuconazonium sulfate, the prodrug of isavuconazole. Following a single-dose administration of radiolabeled isavuconazonium sulfate (labeled on the active moiety), radioactivity was detectable within 1 h postdose in 56 of 65 tissue/fluid specimens. The highest maximum concentrations (Cmax) were observed in bile and liver (66.6 and 24.7 µg eq/g, respectively). The lowest Cmax values were in bone and eye lens (0.070 and 0.077 µg eq/g, respectively). By 144 h postdose, radioactivity was undetectable in all tissues/fluids except liver (undetectable at 336 h) and adrenal gland tissues (undetectable at 672 h). Following daily administration for up to 21 days, 1-h-postdose Cmax values were the highest on or before day 14 in all except seven tissues/fluids, of which only rectum mucosa and small intestine mucosa had Cmax values >25% higher than all other 1-h-postdose values. For 24-h-postdose Cmax values, only large intestine, large intestine mucosa, and urine had the highest Cmax values at day 21. The penetration of single oral doses of unlabeled isavuconazole (25 mg/kg of body weight isavuconazonium sulfate) and voriconazole (50 mg/kg) into rat brain (assessed using liquid chromatography-tandem mass spectrometry) was also compared. Brain concentration/plasma concentration ratios reached approximately 1.8:1 and 2:1, respectively. These data suggest that isavuconazole penetrates most tissues rapidly, reaches a steady state in most or all tissues/fluids within 14 days, does not accumulate in tissues/fluids over time, and achieves potentially efficacious concentrations in the brain.

Morphological and immunohistochemical comparison of intrapancreatic nerves between chronic pancreatitis and type 1 autoimmune pancreatitis.

OBJECTIVES: The abdominal pain associated with chronic pancreatitis (CP) may be related to the increased number and size of intrapancreatic nerves. On the other hand, patients with type 1 autoimmune pancreatitis (AIP) rarely suffer from the pain syndrome, and there are no previous studies concerning the histopathological findings of intrapancreatic nerves in patients with type 1 AIP. The current study is aimed at investigating the differences in the histopathological and immunohistochemical findings of intrapancreatic nerves in patients with CP and type 1 AIP. METHODS: Neuroanatomical differences between CP and type 1 AIP were assessed by immunostaining with a pan-neuronal marker, protein gene product 9.5 (PGP9.5). The number (neural density) and area (neural hypertrophy) of PGP9.5-immunopositive nerves were quantitatively analyzed. Furthermore, the expression of nerve growth factor (NGF), and a high affinity receptor for NGF, tyrosine kinase receptor A (TrkA), was assessed by immunohistochemistry. RESULTS: Both neural density and hypertrophy were significantly greater in pancreatic tissue samples from patients with CP than those with normal pancreas or type 1 AIP. NGF expression was stronger in type 1 AIP than in CP, whereas TrkA expression in type 1 AIP was poorer than in CP. CONCLUSIONS: Although CP and type 1 AIP are both characterized by the presence of sustained pancreatic inflammation, they are different in terms of the density and hypertrophy of intrapancreatic nerve fibers. It is possible that this may be related to the difference in the activity of the NGF/TrkA-pathway between the two types of pancreatitis.

Utility of newly developed short-type double-balloon endoscopy for endoscopic retrograde cholangiography in postoperative patients.

BACKGROUND AND AIM: The utility of conventional short-type double-balloon endoscopy (DBE) for pancreatobiliary disease in patients with postoperative anatomy had been widely acknowledged and accepted. However, some technical difficulties yet remained. In an attempt to solve these problems, the new short-type DBE (N-short DBE) was uniquely designed for therapeutic endoscopic retrograde cholangiography (ERC) in postoperative patients. The aim of this study was to evaluate the usefulness of N-short DBE for ERC in postoperative patients. METHODS: From August 2015 to April 2016, ERC using N-short DBE (DB-ERC) was performed in 100 postoperative patients (112 procedures). We retrospectively studied the success rate of reaching the blind end, the median time to reach the blind end, the diagnostic success rate, the therapeutic success rate, the median time to complete ERC-related interventions, the overall success rate, the median time to complete DB-ERC, and adverse events. RESULTS: The success rate of reaching the blind end was 99.1%. The median time to reach the blind end was 10 min (interquartile range [IQR], 6-19 min). The diagnostic success rate was 98.2%. The therapeutic success rate was 100%. The median time to complete ERC-related interventions was 36 min (IQR, 22-62 min). The overall DB-ERC success rate was 97.3%. The median time to complete DB-ERC was 54 min (IQR, 37-73 min). The occurrence of adverse events was 2.7%. CONCLUSIONS: The N-short DBE for ERC in postoperative patients is useful and safe. DB-ERC is promising therapeutic modality in such patients and should be selected as the first-line policy.

A body mass index ≥25 kg/m2 is associated with a poor prognosis in patients with acute pancreatitis: a study of Japanese patients.

BACKGROUND: In Asian population, there is limited information on the relevance between obesity and poor outcomes in acute pancreatitis (AP). The objective of this study was to examine the clinical impact of obesity based on body mass index (BMI) on prognosis of AP in Japanese patients. METHODS: A total of 116 patients with AP were enrolled in this study. Univariate and multivariate logistic regression analyses were performed to examine relations between BMI and patients' outcomes. Additionally, to investigate whether including obesity as a prognostic factor improved the predictive accuracy of a Japanese prognostic factor score (PF score), a receiver-operating characteristic (ROC) curve analysis of mortality was conducted. RESULTS: Multiple logistic regression analyses revealed that BMI =25 kg/m2 was associated with a significant higher mortality [odds ratio (OR)=15.8; 95% confidence interval (CI): 1.1-227; P=0.043]. The area under the ROC curve (AUC) for the combination of PF score and BMI =25 kg/m2 (AUC=0.881; 95% CI: 0.809-0.952) was higher than that for the PF score alone (AUC=0.820; 95% CI: 0.713-0.927) (P=0.034). CONCLUSIONS: The negative impact of a high BMI on the prognosis of AP was confirmed in a Japanese population. Including BMI =25 kg/m2 as an additional parameter to PF score enhanced the predictive value of the PF score for AP-related mortality.

Anatomic characterization of the humeral nutrient artery: Application to fracture and surgery of the humerus.

Anatomic characterization of the humeral nutrient artery varies among the several textbooks on human anatomy. To clarify the anatomic characteristics of the humeral nutrient artery, we reexamined its origin and course by cadaveric dissection. In typical cases, one prominent nutrient foramen was situated on the anteromedial surface of the humeral shaft, and the nutrient canal distally penetrated the cortical bone layer. The humeral nutrient artery originated from the brachial artery below the level of the nutrient foramen as a short ascending branch. On reaching near the nutrient foramen, the humeral nutrient artery formed a hairpin loop on the periosteum to enter into the nutrient foramen. In some cases, an accessory nutrient foramen was also found near the groove for the radial nerve on the posterior surface of the humerus. This accessory nutrient foramen received an accessory humeral nutrient artery that originated from the radial collateral artery. The present findings corresponded well with the descriptions in the anatomy textbooks published in English-speaking countries. However, textbooks published in German-speaking countries describe only one type of humeral nutrient artery, the branch of the profunda brachii artery. Terminologia Anatomica, the international standard in human anatomic terminology, most likely adopted the description in the German anatomy textbooks, and thus, it is necessary to correct the position of the humeral nutrient artery in the hierarchy of Terminologia Anatomica for accurate morphological description. Clin. Anat. 30:978-987, 2017. © 2017 Wiley Periodicals, Inc.

History of Western Artistic Anatomy in the 19th Century: Prehistory of Artistic Anatomy in Japan.

The study of artistic anatomy was established in the 17th century, and its education techniques were developed in the 19th century and brought to Japan in the Meiji era. Books of artistic anatomy published in the 19th century have been collected and classified into three periods. In the early period before 1828, education of artistic anatomy proper was preliminarily tried, and in the middle period before 1869, new educational methods were invented to adapt the education in the curriculum of the artistic academy. In the late period, various educational methods of artistic anatomy were combined and systematized to provide modem educational materials which are still in use. Medical illustration was developed in the 20th century, and is clearly distinguished from artistic anatomy. The present study reveals the genealogy of Western artistic anatomy as well as the historical background of artistic anatomy in Japan.

Obstructive Sleep Apnea as Possible Causal Factor for Visit-to-Visit Blood Pressure Variability.

BACKGROUND: Recent studies have shown that visit-to-visit blood pressure variability (BPV) is an independent risk factor for cardiovascular disease. However, it has not been clarified whether obstructive sleep apnea (OSA) is associated with visit-to-visit BPV. METHODS AND RESULTS: The 56 subjects with OSA and 26 control subjects without OSA were examined. Office BP was measured on 5 separate consecutive occasions prior to a polysomnography examination. The visit-to-visit BPV was expressed as the standard deviation and the coefficient of variation of the 5 systolic BP measurements. In subjects with an apnea-hypopnea index (AHI) of more than 20 episodes per hour, the visit-to-visit BPV was also measured after the start of continuous positive airway pressure (CPAP) therapy. Overall, the AHI positively correlated with the standard deviation and the coefficient of variation of systolic BP. In a multivariate analysis, the plasma noradrenaline level and the AHI were independently and positively correlated with the standard deviation and the coefficient of variation of the systolic BP. Among the patients who underwent CPAP therapy, good adherence with CPAP therapy significantly reduced the visit-to-visit BPV. CONCLUSIONS: OSA is associated with abnormal visit-to-visit BPV and sympathetic activation seems to be related in some way. (Circ J 2016; 80: 1787-1794).

Murine Cyp3a knockout chimeric mice with humanized liver: prediction of the metabolic profile of nefazodone in humans.

Chimeric mice with humanized livers (PXB mice) are used to investigate the metabolism and pharmacokinetics of drugs in humans. However, residual murine enzymatic activities derived from the liver and the presence of mouse small intestinal metabolism can hamper the prediction of human drug metabolism. Recently murine Cytochrome P450 3a gene knockout chimeric mice with humanized livers (Cyp3a KO CM) were developed. To evaluate the prediction of drug metabolism, nefazodone (NEF) was administered orally at 10 mg/kg to the following mouse strains: Cyp3a KO CM, murine Cyp3a gene knockout (Cyp3a KO), PXB and severe combined immunodeficiency (SCID) mice. Liquid chromatography-mass spectrometry was used for metabolic profiling of plasma, urine and bile. The prediction of human metabolite levels such as hydroxy nefazodone (OH-NEF), triazoledione form (TD), m-chlorophenylpiperazine and dealkyl metabolites in Cyp3a KO CM was superior to that in Cyp3a KO, PXB or SCID mice. Further, clinical exposure levels of NEF, OH-NEF and TD were reproduced in Cyp3a KO CM. In contrast, NEF was rapidly metabolized to TD in both PXB and SCID mice but not in Cyp3a KO mice, suggesting that murine CYP3A is involved in the elimination of NEF in these mice. These findings demonstrate that the metabolic profile of NEF in Cyp3a KO CM differs qualitatively and quantitatively from that in PXB mice due to the higher metabolic rate of NEF and its metabolites via murine CYP3A. Therefore Cyp3a KO CM might be useful in predicting the metabolic profiles of drug candidates in humans.

Development of Murine Cyp3a Knockout Chimeric Mice with Humanized Liver.

We developed murine CYP3A knockout ko chimeric mice with humanized liver expressing human P450S similar to those in humans and whose livers and small intestines do not express murine CYP3A this: approach may overcome effects of residual mouse metabolic enzymes like Cyp3a in conventional chimeric mice with humanized liver, such as PXB-mice [urokinase plasminogen activator/severe combined immunodeficiency (uPA/SCID) mice repopulated with over 70% human hepatocytes] to improve the prediction of drug metabolism and pharmacokinetics in humans. After human hepatocytes were transplanted into Cyp3a KO/uPA/SCID host mice, human albumin levels logarithmically increased until approximately 60 days after transplantation, findings similar to those in PXB-mice. Quantitative real-time-polymerase chain reaction analyses showed that hepatic human P450s, UGTs, SULTs, and transporters mRNA expression levels in Cyp3a KO chimeric mice were also similar to those in PXB-mice and confirmed the absence of Cyp3a11 mRNA expression in mouse liver and intestine. Findings for midazolam and triazolam metabolic activities in liver microsomes were comparable between Cyp3a KO chimeric mice and PXB-mice. In contrast, these activities in the intestine of Cyp3a KO chimeric mice were attenuated compared with PXB-mice. Owing to the knockout of murine Cyp3a, hepatic Cyp2b10 and 2c55 mRNA levels in Cyp3a KO/uPA/SCID mice (without hepatocyte transplants) were 8.4- and 61-fold upregulated compared with PXB-mice, respectively. However, human hepatocyte transplantation successfully restored Cyp2b10 level nearly fully and Cyp2c55 level partly (still 13-fold upregulated) compared with those in PXB-mice. Intestinal Cyp2b10 and 2c55 were also repressed by human hepatocyte transplantation in Cyp3a KO chimeric mice.

Fluorescence cytology with 5-aminolevulinic acid in EUS-guided FNA as a method for differentiating between malignant and benign lesions (with video).

BACKGROUND: EUS-guided FNA (EUS-FNA) has been increasingly performed to obtain specimens for the pathological evaluation of patients with GI and pancreaticobiliary masses as well as lymphadenopathies of unknown origin. Photodynamic diagnosis by using 5-aminolebulinic acid (ALA) has been reported to be useful for enabling the visual differentiation between malignant and normal tissue in various cancers. OBJECTIVE: To evaluate the diagnostic accuracy of fluorescence cytology with ALA in EUS-FNA. DESIGN: A prospective study. SETTING: A single center. PATIENTS: A total of 28 consecutive patients who underwent EUS-FNA for the pathological diagnosis of a pancreaticobiliary mass lesion or intra-abdominal lymphadenopathy of unknown origin. INTERVENTIONS: Patients were orally administered ALA 3 to 6 hours before EUS-FNA. The sample was obtained via EUS-FNA for fluorescence cytology and conventional cytology. A single gastroenterologist performed the fluorescence cytology by using fluorescence microscopy after the procedure, independently of the conventional cytology by pathologists. MAIN OUTCOME MEASUREMENTS: The accuracy of fluorescence cytology with ALA in the differentiation between benign and malignant lesions by comparing the results of fluorescence cytology with the final diagnosis. RESULTS: Of the 28 patients included in the study, 22 were considered as having malignant lesions and 6 patients as having benign lesions. Fluorescence cytology could correctly discriminate between benign and malignant lesions in all patients. Therefore, both the sensitivity and specificity of fluorescence cytology were 100% in our study. LIMITATIONS: Fluorescence cytology was performed by only 1 gastroenterologist with a small number of patients. CONCLUSION: Fluorescence cytology with ALA in EUS-FNA may be an effective and simple method for differentiating between benign and malignant lesions.

Synthesis, structure-activity relationships, and anticonvulsant activities of 2-amino-4H-pyrido[3,2-e][1,3]thiazin-4-one derivatives as orally active AMPA receptor antagonists.

As part of a program aimed at discovering orally active 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor antagonists, we screened our compound library and identified 2-[allyl(4-methylphenyl)amino]-4H-pyrido[3,2-e][1,3]thiazin-4-one (7) as a lead compound that inhibited kainate-induced neurotoxicity mediated by AMPA receptors in rat hippocampal cultures. Structure-activity relationship studies of a series of 2-amino-4H-pyrido[3,2-e][1,3]thiazin-4-one derivatives revealed that substituents on the phenyl ring attached to the 2-amino group and the 4H-pyrido[3,2-e][1,3]thiazin-4-one ring system play an important role in inhibitory activity against kainate-induced neurotoxicity. Several analogs bearing a phenyl group with a 4-substituent or five- or six-membered ring fused at the 3,4-positions exhibited potent inhibitory activity against kainate-induced neurotoxicity. Further, some of these compounds exhibited significant suppression of maximal electroshock seizure in mice following oral administration. Of these compounds, 2-[(4-chlorophenyl)(methyl)amino]-4H-pyrido[3,2-e][1,3]thiazin-4-one (16i) (YM928) demonstrated the most potent inhibitory effect with an ED50 value of 7.4mg/kg.

Continuous positive airway pressure treatment improves cardiovascular outcomes in elderly patients with cardiovascular disease and obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular disease (CVD), particularly in the middle-aged population. However, the clinical importance of OSA as a risk for CVD in the elderly population remains controversial. Moreover, evidence for the effectiveness of continuous positive airway pressure (CPAP) treatment for the secondary prevention of CVD in elderly patients is lacking. We assessed whether CPAP treatment improves cardiovascular outcomes in elderly patients with OSA and CVD. In this retrospective cohort study, we enrolled 130 elderly patients aged 65-86 years with moderate to severe OSA (apnea-hypopnea index ≥15/h) and a history of hospitalization due to CVD, who underwent polysomnography between November 2004 and July 2011. Patients were divided into the CPAP group (n = 64) or untreated OSA group (n = 66). The main outcome measures were cardiovascular death and hospitalization due to CVD. During the mean follow-up period of 32.9 ± 23.8 (standard deviation) months, 28 (21.5 %) patients either died or were hospitalized. The Kaplan-Meier curves indicated that event-free survival was significantly lower in the untreated OSA group than in the CPAP group (P < 0.005). A multivariate analysis showed that the risk was significantly increased in the untreated OSA group (hazard ratio 5.13; 95 % confidence interval 1.01-42.0; P < 0.05). Moderate to severe OSA not treated with CPAP was an independent risk factor for relapse of a CVD event, and adequate CPAP treatment improved cardiovascular outcomes in elderly patients.