Pharyngeal Haemorrhage Immediately After Intake of Fried Foods: Angina Bullosa Haemorrhagica.

Angina bullosa haemorrhagica (ABH) is a disease of unknown cause that occurs most frequently in middle-aged and older adults and is characterized by the destruction of blood vessels in the submucosal layer of the middle pharynx and larynx centred on the soft palate, resulting in the formation of haemorrhagic blisters. It usually resolves within a day and heals without scarring within about a week. No treatment is necessary. However, cases of airway obstruction due to haematemesis have been reported, and this potential risk should be considered when tracheal intubation or upper gastrointestinal endoscopy is being performed. In this report, we describe the case of a 50-year-old man who developed a haematoma in the pharynx following upper endoscopy, which spontaneously ruptured and healed, leading to the diagnosis of ABH. The main purpose of this case report is to remind the reader that ABH improves without treatment, thus eliminating the need for unnecessary examination, and that there is a risk of airway obstruction depending on the site of the lesion. LEARNING POINTS: The key to the diagnosis of angina bullosa haemorrhagica (ABH) is a history of acute haemorrhagic vesicles caused by an external stimulus such as food or intubation, which resolve without scarring within a week or so.ABH can occur at any oropharyngeal site, but its occurrence in the pharyngeal region raises the risk of airway obstruction due to haematemesis.

Hybrid PBL and Pure PBL: Which one is more effective in developing clinical reasoning skills for general medicine clerkship?-A mixed-method study.

This study aims to compare the effectiveness of Hybrid and Pure problem-based learning (PBL) in teaching clinical reasoning skills to medical students. The study sample consisted of 99 medical students participating in a clerkship rotation at the Department of General Medicine, Chiba University Hospital. They were randomly assigned to Hybrid PBL (intervention group, n = 52) or Pure PBL group (control group, n = 47). The quantitative outcomes were measured with the students' perceived competence in PBL, satisfaction with sessions, and self-evaluation of competency in clinical reasoning. The qualitative component consisted of a content analysis on the benefits of learning clinical reasoning using Hybrid PBL. There was no significant difference between intervention and control groups in the five students' perceived competence and satisfaction with sessions. In two-way repeated measure analysis of variance, self-evaluation of competency in clinical reasoning was significantly improved in the intervention group in "recalling appropriate differential diagnosis from patient's chief complaint" (F(1,97) = 5.295, p = 0.024) and "practicing the appropriate clinical reasoning process" (F(1,97) = 4.016, p = 0.038). According to multiple comparisons, the scores of "recalling appropriate history, physical examination, and tests on clinical hypothesis generation" (F(1,97) = 6.796, p = 0.011), "verbalizing and reflecting appropriately on own mistakes," (F(1,97) = 4.352, p = 0.040) "selecting keywords from the whole aspect of the patient," (F(1,97) = 5.607, p = 0.020) and "examining the patient while visualizing his/her daily life" (F(1,97) = 7.120, p = 0.009) were significantly higher in the control group. In the content analysis, 13 advantage categories of Hybrid PBL were extracted. In the subcategories, "acquisition of knowledge" was the most frequent subcategory, followed by "leading the discussion," "smooth discussion," "getting feedback," "timely feedback," and "supporting the clinical reasoning process." Hybrid PBL can help acquire practical knowledge and deepen understanding of clinical reasoning, whereas Pure PBL can improve several important skills such as verbalizing and reflecting on one's own errors and selecting appropriate keywords from the whole aspect of the patient.

Group B Streptococcus Bacteremia Mimicking Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) Syndrome.

Group B Streptococcus (GBS) causes septic arthritis in healthy adults, and a significant number of GBS septic arthritis cases involve multiple joints. Nevertheless, septic arthritis is commonly monoarticular. Here, we report a case of a 45-year-old man who complained of subacute fever and right shoulder and right buttock pain for three weeks despite undergoing garenoxacin treatment for one week. Although synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome could be a possible differential diagnosis for this patient, the fever and subacute clinical course could not be explained. Blood cultures revealed the presence of GBS; therefore, he was diagnosed with septic arthritis. After antibiotic treatment for six weeks, his symptoms resolved.

Does scoring patient complexity using COMPRI predict the length of hospital stay? A multicentre case-control study in Japan.

OBJECTIVE: To clarify the factors associated with prolonged hospital stays, focusing on the COMplexity PRediction Instrument (COMPRI) score's accuracy in predicting the length of stay of newly hospitalised patients in general internal medicine wards. DESIGN: A case-control study. SETTING: Three general internal medicine wards in Chiba Prefecture, Japan. PARTICIPANTS: Thirty-four newly hospitalised patients were recruited between November 2017 and December 2019, with a final analytic sample of 33 patients. We included hospitals in different cities with general medicine outpatient and ward facilities, who agreed to participate. We excluded any patients who were re-hospitalised within 2 weeks of a prior discharge. PRIMARY AND SECONDARY OUTCOME MEASURES: Patients' COMPRI scores and their consequent lengths of hospital stay. RESULTS: The 17 patients (52%) allocated to the long-term hospitalisation group (those hospitalised ≥14 days) had a significantly higher average age, COMPRI score and percentage of participants with comorbid chronic illnesses than the short-term hospitalisation group (<14 days). A logistic regression model (model A, comprising only the COMPRI score as the explanatory variable) and a multiple logistic regression model (model B, comprising variables other than the COMPRI score as explanatory variables) were created as prediction models for the long-term hospitalisation group. When age ≥75 years, a COMPRI score ≥6 and a physician with 10 years' experience were set as explanatory variables, model A showed better predictive accuracy compared with model B (fivefold cross-validation, area under curve of 0.87 vs 0.78). The OR of a patient with a COMPRI score of ≥6 joining the long-term hospitalisation group was 4.25 (95% CI=1.43 to 12.63). CONCLUSIONS: Clinicians can use the COMPRI score when screening for complexity assessment to identify hospitalised patients at high risk of prolonged hospitalisation. Providing such patients with multifaceted and intensive care may shorten hospital stays.

Giant frontal lobe meningioma.

A 90-year-old woman presented with gradual onset of generalized weakness, imbalance, urinary incontinence, progressive impairment of memory, and deviant sexual behavior. The Reversed Hasegawa's Dementia Scale, a brief cognitive scale, was 13 (dementia cutoff point of 21/20).

Concurrent chemoradiotherapy with intravenous cisplatin and docetaxel for advanced oral cancer.

Concurrent chemoradiotherapy (CCRT) is a common treatment for advanced oral cancer, and its efficacy has been reported in many reviews. We have performed concurrent CCRT with intravenous cisplatin and docetaxel in patients with advanced oral cancer. The purpose of this report was to evaluate this treatment and to compare the outcome of this treatment with that of standard CCRT treatments for advanced head and neck cancer using intravenous administration. The patients were treated for primary advanced oral squamous cell carcinoma in our department between February 2003 and November 2015. In all, 17 patients (14 men, 3 women) with stage III (2 patients) stage IVA (10 patients), and stage IVB (5 patients) oral cancer were treated. The patient ages ranged from 44 to 87 years (average age: 65.4 years). The follow-up duration ranged from 5 to 117 months (average follow-up duration: 41 months, median follow-up duration: 39 months). The primary cancer sites were the maxillary gingiva (7 cases), mandible gingiva (3 cases), buccal mucosa (3 cases), tongue (3 cases), and floor of the mouth (1 case). The 3-year and 5-year survival rates were 52.9% and 33.0%, respectively, and both the 3-year and 5-year locoregional control rates were 50.9% as determined by the Kaplan-Meier method. The response rate was 94% (CR: 8 cases: 47% and PR: 8 cases: 47%). The incidences of toxicity greater than grade 3 included dermatitis and stomatitis in 9 cases each (52.9%), anemia in 3 cases (18.7%) and liver dysfunction in 1 case (6.2%). We found that the results of this therapy were equivalent to those of standard CCRT treatments for advanced head and neck cancer using intravenous administration, and the incidences of toxicity were lower than those of standard treatments. These findings suggested that this treatment is safe and useful for advanced oral cancer.

Comparison of clinical outcomes following percutaneous coronary intervention versus optimal medical therapy based on gray-zone fractional flow reserve in stable angina patients with intermediate coronary artery stenosis (COMFORTABLE prospective study): Study protocol for a multicenter randomized controlled trial.

BACKGROUND: Even in the current drug-eluting stent era, revascularization for coronary stenosis with fractional flow reserve (FFR) between 0.75 and 0.80, the so-called "gray zone," is a matter of debate. Previous studies have reported conflicting results regarding outcomes of revascularization versus deferral for coronary stenosis when FFR values are in the gray zone, but these studies have had differing designs and populations. We therefore will investigate whether medical therapy plus percutaneous coronary intervention (PCI) is superior to medical therapy alone in reducing major cardiovascular events in patients presenting with coronary stenosis with gray zone FFR values. METHODS/DESIGN: This is a prospective, multicenter, open-label, parallel group, randomized, controlled, superiority study. A total of 410 eligible participants will be recruited and randomized to either the medical therapy plus PCI group or the medical therapy alone group. The primary endpoint is 1-year major adverse cardiac events (MACEs), defined as a combined endpoint of all-cause death, nonfatal myocardial infarction (MI), or unplanned target vessel revascularization (TVR). Secondary endpoints include MACE at 2 and 5 years. Moreover, each individual component of the primary endpoint, cardiovascular death, target vessel-related and non-target vessel-related MI, all MI, clinically driven TVR or non-TVR, all revascularization, stent thrombosis, and angina symptom status will be evaluated at 1, 2, and 5 years. DISCUSSION: This is the first prospective, multicenter, randomized, controlled study to investigate the superiority of medical therapy plus PCI over medical therapy by itself in reducing major cardiovascular events in patients presenting with coronary stenosis with "gray zone" FFR values. The results will help interventional cardiologists in making revascularization decisions regarding coronary stenosis with gray zone FFR values. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000031526 . Registered on 1 March 2018.

Fatal necrotizing myositis from fulminant Streptococcus dysgalactiae subspecies equisimilis (SDSE) infection: A case report of autopsy images.

Over the past few decades, Streptococcus dysgalactiae subspecies equisimilis (SDSE) have been considered as weak pathogenicity compared with S. pyogenes (GAS). Some recent reports argue that SDSE may bring severe soft tissue infection as same as GAS. No reports have been tried to reveal the clinical characteristics and autopsy images of fulminant SDSE infection. In this case report, we aimed to present a case of fatal necrotizing myositis from fulminant SDSE infection at iliopsoas, including autopsy appearance.

Synthesis of single-phase L10-FeNi magnet powder by nitrogen insertion and topotactic extraction.

Tetrataenite (L10-FeNi) is a promising candidate for use as a permanent magnet free of rare-earth elements because of its favorable properties. In this study, single-phase L10-FeNi powder with a high degree of order was synthesized through a new method, nitrogen insertion and topotactic extraction (NITE). In the method, FeNiN, which has the same ordered arrangement as L10-FeNi, is formed by nitriding A1-FeNi powder with ammonia gas. Subsequently, FeNiN is denitrided by topotactic reaction to derive single-phase L10-FeNi with an order parameter of 0.71. The transformation of disordered-phase FeNi into the L10 phase increased the coercive force from 14.5 kA/m to 142 kA/m. The proposed method not only significantly accelerates the development of magnets using L10-FeNi but also offers a new synthesis route to obtain ordered alloys in non-equilibrium states.

Glutamatergic modulation of noradrenaline release in the rat median preoptic area.

The present study was carried out to investigate whether glutamatergic receptor mechanisms modulate the release of noradrenaline (NA) in the region of the median preoptic nucleus (MnPO) using intracerebral microdialysis techniques in freely moving rats. Perfusion of N-methyl-d-asparatate (NMDA, 10 and 50µM) through the microdialysis probe significantly enhanced dialysate NA concentration in the region of the MnPO. Local perfusion of the NMDA antagonist dizocilpine (MK801, 10 and 50µM) did not change the basal release of NA in the MnPO area. MK801 (10µM) administered together with NMDA antagonized the stimulant effect of NMDA (50µM). Perfusion of the non-NMDA agonist quisqualic acid (QA, 10 and 50µM) or kainic acid (KA, 10 and 50µM) significantly increased the NA release in the MnPO area. Perfusion of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 and 50µM) had no effect on the NA release. CNQX (10µM) administered together with either QA (50µM) or KA (50µM) in the MnPO area prevented the stimulant effect of the agonists on the NA release. Nonhypotensive hypovolemia following subcutaneous injections of polyethylene glycol (PEG, 30%, 5ml) significantly elevated the NA level in the MnPO area. The PEG-induced elevation in the NA release was attenuated by perfusion of either MK801 (10µM) or CNQX (10µM). The present results suggest that glutamatergic synaptic inputs may act to enhance the release of NA in the MnPO area through both NMDA and non-NMDA receptors, and imply that these glutamatergic receptor mechanisms may be involved in the noradrenergic reguratory system for the body fluid balance.

Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of ST-Segment-Elevation Myocardial Infarction.

OBJECTIVE: Early clinical presentation of ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction affects patient management. Although local inflammatory activities are involved in the onset of MI, little is known about their impact on early clinical presentation. This study aimed to investigate whether local inflammatory activities affect early clinical presentation. APPROACH AND RESULTS: This study comprised 94 and 17 patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris, respectively. We simultaneously investigated the culprit lesion morphologies using optical coherence tomography and inflammatory activities assessed by shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary circulation before and after stenting. Prevalence of plaque rupture, thin-cap fibroatheroma, and lipid arc or macrophage count was higher in patients with STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was frequently observed in STEMI compared with others. Local MMP-9 levels were significantly higher than systemic levels (systemic, 42.0 [27.9-73.2] ng/mL versus prestent local, 69.1 [32.2-152.3] ng/mL versus poststent local, 68.0 [35.6-133.3] ng/mL; P<0.01). Poststent local MMP-9 level was significantly elevated in patients with STEMI (STEMI, 109.9 [54.5-197.8] ng/mL versus non-STEMI: 52.9 [33.0-79.5] ng/mL; stable angina pectoris, 28.3 [14.2-40.0] ng/mL; P<0.01), whereas no difference was observed in the myeloperoxidase level. Poststent local MMP-9 and the presence of red thrombus are the independent determinants for STEMI in multivariate analysis. CONCLUSIONS: Local MMP-9 level could determine the early clinical presentation in patients with MI. Local inflammatory activity for atherosclerosis needs increased attention.

Anxiolytic and hypnotic effects in mice of roasted coffee bean volatile compounds.

To clarify the relationship between the volatile compounds present in roasted coffee beans and psychological stress, we investigated the stress-reducing potential of coffee volatiles in mice using a variety of behavioral pharmacology methods. In the elevated plus-maze test, exposure to coffee volatiles increased the time spent in and the number of entries into the open arms without increasing spontaneous locomotor activity. Pentobarbital-induced sleep time was prolonged by volatile exposure. No significant effects were detected in the open-field or forced-swim tests. These results suggest that coffee volatiles lower the arousal level and exert anti-anxiety-like, stress-reducing effects in mice.

Primary sensory neurons with dichotomizing axons projecting to the facet joint and the low back muscle in rats.

BACKGROUND: Clinically, the origin of low back pain is unknown. The pain may originate from the lumbar muscles directly, or it may be referred pain from the spine. Dorsal root ganglion (DRG) neurons with dichotomizing axons have been reported in several species and are thought to be related to referred pain. However, these neurons, which have dichotomizing axons to the lumbar facet joints and to the lumbar muscle, have not been fully investigated. METHODS: Two neurotracers - 1,1'-dioctadecyl-3,3,3',3'- tetramethyl-indocarbocyanine perchlorate (DiI) and fluorogold (FG) - were used in the present double-labeling study. DiI crystals were placed in the right L5/6 facet joint, and FG was applied to right multifidus muscles at the L5 level in 10 rats. Two weeks later, bilateral DRGs from L1 through L6 were harvested, sectioned, and observed under a fluorescence microscope. RESULTS: DiI-labeled DRG neurons innervating the L5/6 facet joint (5.17% of the total DRG neurons) were distributed from L1 to L6. FG-labeled DRG neurons innervating the lower back muscle (15.9% of the total) were also distributed from L1 to L6. Double-labeled DRG neurons were found from L1 to L6. The ratio of total double-labeled/total DiI-labeled DRG neurons was 17% and that of total double-labeled/total FG-labeled DRG neurons was 7%. Approximately 17% of all DRG neurons innervating the facet joints had other axons that extended to the lower back muscle. CONCLUSIONS: This finding provides a possible neuroanatomical explanation for referred low back muscle pain from the lower facet joints.

Low affinity NGF receptor (p75 neurotrophin receptor) inhibitory antibody reduces pain behavior and CGRP expression in DRG in the mouse sciatic nerve crush model.

Nerve growth factor (NGF) and its low-affinity receptor, p75 neurotrophin receptor (p75 NTR), are important mediators of pain. To explore further the mechanisms involved, we examined suppression of pain behavior and expression of neuropeptides such as calcitonin gene-related peptide (CGRP) using a p75 NTR inhibitory antibody, in a mouse sciatic nerve crush model. In the nerve-injured model, 150 microg of a p75 NTR inhibitory antibody or 10 microl of saline were applied. The sciatic nerve in the sham-operated group was uninjured. Mechanical allodynia was measured for 2 weeks. CGRP and p75 NTR expression in L5 dorsal root ganglions (DRGs) was examined immunohistochemically. Mechanical allodynia was found in the two nerve injured groups, but not in the sham-operated group (p < 0.05). However, the magnitude of the mechanical allodynia was significantly decreased after application of p75 NTR inhibitory antibody (p < 0.05). CGRP and p75 NTR immunoreactivity in the L5 DRG neurons was upregulated in the injured nerve groups compared with the sham-operated group; however, p75 NTR inhibitory antibody decreased the CGRP and p75 NTR expression (p < 0.01). Application of the p75 NTR inhibitory antibody to the pinched sciatic nerve suppressed CGRP and p75 NTR expression and pain behavior.

Direct single injection of p38 mitogen-activated protein kinase inhibitor does not affect calcitonin gene-related peptide expression in dorsal root ganglion neurons innervating punctured discs in rats.

STUDY DESIGN.: Immunohistological analysis of punctured disc after application of a p38 MAP kinase inhibitor. OBJECTIVE.: To examine effect of direct application on dorsal root ganglion (DRG) neurons innervating damaged rat discs. SUMMARY OF BACKGROUND DATA.: Degeneration of lumbar discs is one cause of low back pain. Pathogenesis may involve sensory nerve ingrowth into disc inner layers; tumor necrosis factor-alpha (TNF-alpha) is thought to be a major inducer of ingrowth. Because p38 mitogen-activated protein kinase (p38) upregulates TNF-alpha expression and may play a crucial role in pain sensation, we investigated the effect of one injection of inhibitor on expression of the pain-related neuropeptide calcitonin gene-related peptide (CGRP). METHODS.: The neuro-tracer fluoro-gold was applied to the surfaces of L4/5 discs to label the innervating DRG neurons (n = 30). Of 30 rats, 10 were controls, whereas the other 20 were the experimental model (i.e., discs were punctured with 23-gauge needle). P38 specific inhibitor or saline was applied simultaneously (n = 10 each, Puncture + inhibitor and puncture + saline groups). Fourteen days postsurgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for CGRP. Proportion of CGRP-immunoreactive DRG neurons was evaluated in all groups. RESULTS.: Fluoro-gold-labeled neurons innervating the L4/5 disc were distributed throughout L1 to L6 DRGs in all groups. Proportions of labeled neurons positive for CGRP were 15.2% +/- 8% (controls), 27.2% +/- 10% (puncture + saline), and 25.2% +/- 8% (puncture + inhibitor). Proportion of immunoreactive neurons was significantly increased in the puncture groups compared with controls. However, there was no significant difference between the 2 puncture groups (P > 0.1). CONCLUSION.: In this model, CGRP was upregulated in DRG neurons innervating the damaged disc. However, a direct single application of p38 inhibitor did not suppress CGRP expression in innervating DRG neurons. Future research with p38 inhibitor in this model should evaluate multiple or systemic administration of inhibitor.

High-sensitivity C-reactive protein and plaque composition in patients with stable angina pectoris: a virtual histology intravascular ultrasound study.

OBJECTIVE: Elevated high-sensitivity C-reactive protein (hs-CRP) is related to clinical outcome in coronary artery disease. We used virtual histology intravascular ultrasound to evaluate the relationship between serum hs-CRP level and coronary plaque composition in patients with stable angina pectoris. METHODS AND RESULTS: Overall 113 consecutive patients with stable angina pectoris who had a de-novo culprit lesion were examined in this study. Patients were divided into an elevated hs-CRP group (>3 mg/l; n=40) or a normal hs-CRP group (n=73). Grayscale and virtual histology intravascular ultrasound analysis was performed across the entire culprit lesion. Mean plaque area was similar in both groups. Lesion length (18+/-5 vs. 16+/-6 mm, P<0.046) was significantly greater in the elevated hs-CRP group than that in the normal hs-CRP group. Although the percentage of dense calcium, fibrofatty tissue, and fibrous tissue was not different between the two groups, the percentage of necrotic core was significantly greater in the elevated hs-CRP group compared with the normal hs-CRP group (20+/-9 vs. 16+/-8%, P=0.014). The percentage of necrotic core was positively correlated with the serum hs-CRP level (r=0.20, P=0.037). A multivariate logistic regression model showed that the percentage of necrotic core was associated with elevated hs-CRP (P=0.019; odds ratio=1.1; 95% confidence interval=1.01-1.12). CONCLUSION: Elevated hs-CRP was related to the amount of necrotic core in the culprit lesion of stable angina pectoris. Our results suggest that elevated hs-CRP might reflect the inflammatory activity of the coronary atherosclerotic plaque even in the setting of stable angina pectoris.

The effect of endothelial progenitor cells on the development of collateral formation in patients with coronary artery disease.

OBJECTIVE: Unlike arteriogenesis, little is known about the effects of vasculogenesis and its major effector cells, endothelial progenitor cells (EPCs) on collateral formation. In this study, we investigated whether or not the number and function of EPCs were associated with the development of collateral formation in patients with single-vessel coronary artery disease of chronic total occlusion (CTO). METHODS AND RESULTS: The subjects were patients (n=35) undergoing coronary angiography (CAG) who had CTO in one major coronary artery. EPCs were isolated from peripheral blood samples and cultured. Their phenotypes were confirmed by uptake of acetylated LDL and binding of fluorescein isothiocyanate (FITC)-labeled Ulex europaeus agglutinin 1 (UEA-1) lectin. The numbers of colony-forming units (CFUs) and the senescent cells, determined by acidic beta-galactosidase staining, were counted. The angiogenic growth factors from the culture medium were also measured by ELISA. Patients with good collaterals (n=22, Rentrop class 2 and 3) exhibited an increased number of CFUs (p=0.023), reduced number of senescent cells (p=0.010), and higher concentration of b-FGF (0.036) in the culture medium, compared with subjects with poor collaterals (n=13, Rentrop class 0 and 1). CONCLUSION: Our findings suggested that EPC-mediated angiogenesis might be associated with coronary collateral formation in humans.