Effects of mucopolysaccharide polysulphate on tight junction barrier in human epidermal keratinocytes.

Tight junctions (TJs) play important roles in epidermal barrier function and their dysfunction is involved in the pathogenesis of various skin diseases, including atopic dermatitis (AD). Mucopolysaccharide polysulphate (MPS) is the active ingredient of a moisturizing agent used to treat xerosis in patients with AD; however, its mechanism of action on TJ barrier function remains unclear. To elucidate the effects of MPS on TJs, adult human epidermal keratinocyte (HEKa) cells were exposed to MPS, subjected to Western blotting and quantitative PCR analyses for the investigation of TJ-related factors. MPS treatment significantly increased the mRNA and protein expression of claudin-1 (CLDN1) and zonula occludens-1, and significantly increased transepithelial electrical resistance (TEER), which indicates TJ integrity. Conversely, the sulphated and non-sulphated glycosaminoglycans, chondroitin sulphate and hyaluronic acid, respectively, had little effect on TEER or the expression of mRNAs or TJ-related proteins. Interestingly, MPS treatment also inactivated the extracellular signal-regulated kinase signalling pathway, which is known to negatively regulate CLDN1 expression. Furthermore, MPS notably improved the reduction in CLDN1 expression and TEER caused by histamine, which is upregulated in the skin of patients with AD and is known to disrupt the TJ barrier function. Taken together, these findings demonstrate that treatment with the moisturizing agent, MPS, can repair TJ dysfunction and could therefore represent a new therapeutic option for treating patients with AD.

Fatal myopericarditis complicated with coronary vein perforation under the triple antithrombotic therapy: a case report.

BACKGROUND: Acute pericarditis generally follows a mild clinical course and is rarely fatal. Coronary vein involvement is rarely reported. CASE SUMMARY: We report an autopsy case of cardiac tamponade from idiopathic myopericarditis due to coronary venous perforation under the triple antithrombotic therapy. A 69-year-old man was admitted to our hospital with abnormal findings on electrocardiography, bloody pericardial effusion, and mild elevation of troponin I. Oral anti-inflammatories were started and the patient followed a benign course. However, on hospital Day 5, he suddenly suffered cardiogenic shock with pulseless electric activity due to cardiac tamponade under the combination use of the dual antiplatelet drugs and an anticoagulant drug. He died despite intense medical treatment. Autopsy revealed cardiac tamponade caused by perforation in the coronary venous wall. To the best of our knowledge, this is the first description of fatal myopericarditis as a complication of coronary venous perforation. DISCUSSION: The aetiology and mechanism remain unknown; however, we should take care for this rare complication in patients with acute myopericarditis and bloody effusion under the triple antithrombotic therapy.

[Case of Resected Retroperitoneal Dedifferentiated Liposarcoma Extending to the Posterior Mediastinum].

A 71-year-old woman visited our hospital for the examination and treatment of retroperitoneal tumor. CT showed a retroperitoneal tumor extending to the posterior mediastinum; the tumor pressed the IVC and widely abutted the aorta. On MRI, the tumor showed low intensity on T1WI and high intensity on T2WI and DWI. However, the tumor did not show signal reduction on an ADC map. PET-CT showed high accumulation at the tumor. The patient was diagnosed with sarcoma arising from the retroperitoneum. The tumor located on a part of the diaphragm was resected. Histological examination revealed spindle cells with atypical nuclear and multinuclear cells. There were no lesions of well-differentiated liposarcoma. Both CDK4 and MDM2 tested positive on immunohistological staining. Histopathologically, the tumor was diagnosed as dedifferentiated liposarcoma without any well-differentiated liposarcoma component. The postoperative course was uneventful, and she was discharged on the 13th day after surgery. Two months after surgery, no recurrence has been detected.

Characteristics of Transactive Relationship Phenomena among Older adults, Care Workers as Intermediaries, and the Pepper Robot with Care Prevention Gymnastics Exercises.

Healthcare for older adults is a significant problem in Japan and in other developed countries. To address this problem, healthcare robots, now realized, can assist and meet healthcare and welfare practice demands. The aim of this study was to clarify characteristics of Transactive Relationships (TR) in older adults, in care workers as intermediaries, and Pepper (Softbank Robotics Corporation) a robot equipped with the application program of Care Prevention Gymnastics Exercises for Pepper (Pepper-CPGE) made by Xing Company, Japan. Data were collected by observing TRs between Pepper and older patients in Kagawa Prefecture,Japan between from May 8 to August 1 2018. The Transactive Relationship Theory of Nursing (TRETON) was used to explain how Pepper-CPGE led the exercises with older adults as physical exercises. The role of PepperCPGE was to provide instructions for the older adults in performing gymnastic exercises. During the exercising activity, care workers were present to prevent falls of the older adults, and to operate and observe the video presentations by supporting and caring for the participants. In using Pepper-CPGE, it was possible to change the role of the healthcare providers, originally thought to contribute to increasing the quality of older adult care and their rehabilitation. J. Med. Invest. 66 : 46-49, February, 2019.

Risk factors for the development of hypermagnesemia in patients prescribed magnesium oxide: a retrospective cohort study.

BACKGROUND: Magnesium oxide (MgO), an antacid and laxative, is widely used in Japan to treat constipation and peptic ulcers. Because serum Magnesium (Mg) levels are elevated in elderly and/or patients with renal failure, its periodic monitoring is recommended for patients prescribed MgO, in order to prevent MgO-induced hypermagnesemia. However, there is little information regarding the factors contributing to the development of MgO-induced hypermagnesemia. In the present study, we retrospectively investigated the risk factors of hypermagnesemia in patients prescribed MgO. METHODS: Data of 3258 patients hospitalized in Mie University Hospital between October 2015 and September 2017, who were prescribed MgO tablets, were extracted from the electronic medical records. According to the inclusion and exclusion criteria, 320 of the 3258 patients were enrolled in this study. Hypermagnesemia was defined as serum Mg levels ≥2.5 mg/dL (by the Common Terminology Criteria for Adverse Events version 4.0). Uni- and multivariate analyses were performed to identify risk factors for the development of hypermagnesemia in patients prescribed MgO using the following variables: age, estimated glomerular filtration rate, blood urea nitrogen levels, MgO dose, duration of MgO administration, and co-administrated proton pump inhibitors, H2 blocker (famotidine), vitamin D3 drugs, and diuretics. RESULTS: Seventy-five patients out of 320 (23%) developed grade 1 and grade 3 hypermagnesemia, with the occurrence of grade 1 and grade 3 in 62 (19%) and 13 (4%) patients, respectively. Multivariate logistic regression analyses indicated 4 independent risk factors for hypermagnesemia comprising estimated glomerular filtration rate ≤ 55.4 mL/min (odds ratio (OR): 3.105, P = 0.001), blood urea nitrogen ≥22.4 mg/dL (OR: 3.490, P < 0.001), MgO dose ≥1650 mg/day (OR: 1.914, P = 0.039), and duration of MgO administration ≥36 days (OR: 2.198, P = 0.012). The occurrence rate of hypermagnesemia was elevated in accordance with these risk factors. CONCLUSIONS: These results suggest that a periodic monitoring of serum Mg levels is strongly recommended in MgO prescribed patients, especially in those with multiple risk factors for hypermagnesemia. The present findings provide useful information for the safe management of MgO therapy.

[A case of liver Mycobacterium avium complex syndrome, diagnosed by liver biopsy].

A man in his 70s was referred to our hospital for evaluation of low-grade fever, weight loss, and liver dysfunction. Serological tests for viral hepatitis or autoimmune diseases were negative. No significant findings were observed on whole-body computed tomography (CT). Histopathologic examination of a liver biopsy sample revealed a non-caseating granuloma with acid-fast bacillus using the Ziehl-Neelsen stain. Serum Mycobacterium avium complex (MAC) antibody was positive. We started treatment for pulmonary MAC disease. His clinical condition and liver function improved within two months. He was diagnosed with liver MAC disease.

Clinical Utility of Basophil CD203c as a Biomarker for Predicting the Timing of Hypersensitivity Reaction in Carboplatin Rechallenge: Three Case Reports.

PURPOSE: Drug desensitization has been found to be an effective option for carboplatin rechallenge in patients at risk for severe hypersensitivity reaction. However, identifying such patients requires precise clinical tests. This study was performed to evaluate the clinical utility of basophil CD203c to predict the timing of carboplatin-induced severe hypersensitivity reaction. METHODS: Here we report on 3 patients undergoing a carboplatin-desensitization protocol at Mie University Hospital. For all patients, ex vivo exposure to carboplatin resulted in increased levels of activated basophils in a previous occurrence of carboplatin-induced severe hypersensitivity reaction. FINDINGS: Basophil activation test using carboplatin was returned to negative just before the first course of carboplatin-desensitization protocol in all patients, and they successfully received their first course of the protocol with no signs of anaphylaxis. However, for all of the patients, increased basophil activation was once again detected after subsequent readministration of carboplatin and grade 3 or 4 anaphylaxis developed. Basophil activation test coincided precisely with the timing of carboplatin-induced anaphylaxis in all patients. IMPLICATIONS: CD203c basophil activation testing might prove to be a reliable tool for risk stratification and clinical decision making for carboplatin desensitization in which severe hypersensitivity reaction is likely to occur.

Surveillance of short-segment Barrett's esophagus using ultrathin transnasal endoscopy.

BACKGROUND AND AIM: Newly developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. We conducted surveillance of subjects with Barrett's esophagus using this ultrathin transnasal endoscopy. In Japan the lower margin of the lower esophageal palisade vessels is defined the gastroesophageal junction in deep inspiration. We diagnose Barrett's esophagus if columnar epithelium is present on the oral side of the gastroesophageal junction. METHODS AND RESULTS: Barrett's esophagus was confirmed in 116 out of 135 subjects (85.9%), with 17 cases of short-segment Barrett's esophagus (SSBE) and 99 of ultra-short-segment Barrett's esophagus. Close observation of the Barrett's esophagus mucosal structural pattern using narrow band imaging revealed 29 cases with an oval or round pattern, 29 with a long straight pattern, 47 with a villous pattern, 8 with a cerebriform pattern, and 6 with an irregular pattern according to Goda classification. Mucosal biopsies from all subjects with SSBE are examined. Histological examination revealed intestinal metaplasia in only eight subjects. We grouped the oval/round and long straight patterns as closed type, and the villous, cerebriform, and irregular patterns as open type. Analysis of the relationship between these mucosal patterns and background factors revealed a significant correlation between intestinal metaplasia and the open-type pattern. CONCLUSION: We consider this new ultrathin transnasal endoscopy to be a useful technique for surveillance of Barrett's esophagus, especially SSBE.

Evaluation of gastric cancer diagnosis using new ultrathin transnasal endoscopy with narrow-band imaging: preliminary study.

BACKGROUND AND AIM: The new developed ultrathin transnasal endoscope, the GIF-XP290N, makes possible a resolving power similar to the GIF-H260 at a distance of 3 mm. In this study, using the GIF-XP290N, we evaluated whether endoscopic diagnosis (discrimination between benign and malignant) of gastric lesions is possible using nonmagnified narrow-band imaging (NBI) endoscopy. METHODS: The subjects were 255 consecutive patients who underwent screening of the gastrointestinal tract using new ultrathin transnasal endoscopy. Their average age was 65.2 ± 11.4 years. The male-female ratio was 2.5:1. All cases were examined using conventional white-light imaging (WLI) and nonmagnified NBI. When a depressed lesion was detected in the stomach, it was examined using WLI, then NBI close examination (at about 3 mm). We observed the mucosal structure of the lesion using close visualization with NBI. Concerning mucosal structural changes, we looked for a clear demarcation line between the lesion and the surrounding mucosa, and loss, irregularity, or nonuniformity of the lesion mucosal microsurface pattern. RESULTS: A total of 52 depressed lesions were examined. The histological diagnosis was cancer for 8 lesions, and noncancer for 44 lesions. WLI examination yielded a sensitivity of 50.0% (4/8), specificity of 63.6% (28/44), and accuracy 61.5% (32/52). On the other hand, NBI close examination yielded a sensitivity of 87.5% (7/8), specificity of 93.2% (41/44), and accuracy of 92.3% (48/52), significantly higher. CONCLUSION: NBI close examination using ultrathin transnasal endoscopy enables mucosal diagnosis even without magnification and was considered to be an effective technique for improving endoscopic diagnosis.

Carboplatin-induced severe hypersensitivity reaction: role of IgE-dependent basophil activation and FcεRI.

Basophil activation was observed in patients with a history of carboplatin-induced severe hypersensitivity reaction (HR). However, the precise mechanism by which carboplatin induces basophil activation and the associated surrogate markers remains to be elucidated. To investigate whether IgE-dependent mechanisms, including the overexpression of FcεRI, participate in carboplatin-induced basophil activation, 13 ovarian cancer patients were enrolled: 5 with a history of carboplatin-induced severe hypersensitivity reaction within the past 2 years, and 8 with no such history. The expression levels of FcεRI, IgE, and CD203c on basophils were measured using a flow cytometer. Immunoglobulin E-dependent basophil activation was evaluated by testing for IgE passive sensitization using lactic acid, and by testing for phosphatidylinositol 3-kinase inhibition, using wortmannin. In three patients positive for carboplatin hypersensitivity, pretreatment with wortmannin almost completely inhibited carboplatin-induced basophil activation (P < 0.05). In a healthy control subject, whose own IgE showed no response to carboplatin, acquired reactivity to carboplatin when exposed to plasma from patients positive for carboplatin hypersensitivity. This did not occur when the same experiment was carried out using plasma from the patients negative for carboplatin hypersensitivity. Moreover, pretreatment with omalizumab, a monoclonal anti-IgE antibody, almost completely blocked carboplatin-induced basophil activation in the plasma of patients positive for carboplatin hypersensitivity. On further investigation, the HR-positive group had significantly higher levels of FcεRI compared with the negative group (P < 0.05). In conclusion, an IgE-dependent mechanism incorporating FcεRI overexpression participates in carboplatin-induced severe HR. These results establish the relevance of monitoring the pharmacodynamic changes of basophils to prevent carboplatin-induced severe HR.

Severe sleepiness and excess sleep duration induced by paroxetine treatment is a beneficial pharmacological effect, not an adverse reaction.

BACKGROUND: Severe sleepiness and excess sleep duration, "Hypersomnia", induced by paroxetine treatment are generally considered adverse drug reactions, however, our experience indicates that patients with depressive disorder who experience "Hypersomnia" during paroxetine treatment have good clinical response. The aim of this study was to determine if "Hypersomnia" during paroxetine treatment is a beneficial pharmacological effect or an adverse drug reaction, and to investigate the impact of genetic polymorphisms on individual differences in the occurrence of "Hypersomnia" induced by paroxetine. METHODS: A consecutive series of 46 Japanese patients with depressive disorder were treated with paroxetine. Patients who complained of great drowsiness or who slept for more than 12-h per day over seven days were identified as having experienced "Hypersomnia". For the clinical improvement rates and genotype distribution of the circadian locomotor output cycles kaput (CLOCK), serotonin transporter and cytochrome P450 2D6 (CYP2D6), the group that showed "Hypersomnia" induced by paroxetine treatment and the group that did not show "Hypersomnia" were compared statistically. RESULTS: Patients who experienced "Hypersomnia" (17.4%) showed a significantly higher response rate at two weeks than did patients who did not experience "Hypersomnia" (p=0.0127). No significant association between the occurrence of "Hypersomnia" and genetic polymorphisms was found. LIMITATIONS: We cannot exclude the risk of false positive errors due to the relatively small sample sizes. CONCLUSIONS: "Hypersomnia" during paroxetine treatment for depression is a beneficial pharmacological effect, not an adverse drug reaction.

Mucosal cutting biopsy technique for histological diagnosis of suspected gastrointestinal stromal tumors of the stomach.

BACKGROUND AND AIM: The Japanese Gastrointestinal Stromal Tumor (GIST) therapeutic guidelines recommend endoscopic ultrasound-guided fine-needle aspiration biopsy for histological diagnosis. However, before 2010, this technique was only carried out at a minority of medical institutions in Japan. In the present study, we investigated the usefulness of mucosal cutting biopsy. METHODS: In 18 asymptomatic gastric submucosal tumors, mucosal cutting biopsies were carried out. We examined tumor size, tumor site (lower third: L; middle third: M; upper third: U), histopathological diagnostic yield and complications. In cases that proceeded to surgical resection with a diagnosis of GIST, we compared the pre- and postoperative histopathological diagnosis, and the histological degrees of malignancy. RESULTS: The tumors had a mean size of 20.3 mm and were located at the L site in five cases, M in four, and U in nine. Histological diagnosis of submucosal tumor was obtained in all the cases. (GIST, n = 13; heterotopic pancreas, n = 2; and leiomyoma, n = 3). No complications (e.g. bleeding, perforation or peritonitis) were seen after this procedure. In all 11 patients with GIST who underwent surgical resection, the histopathological findings from the mucosal cutting biopsy specimens were similar to those from the surgically resected specimens, with agreement between the immunostaining findings and the histological degree of malignancy (90.9%) in 10 patients. CONCLUSIONS: The mucosal cutting biopsy technique is a useful diagnostic modality for the diagnosis of gastric GIST and for selection of the appropriate treatment.

Upper gastrointestinal complications induced by anti-platelet agents.

Low-dose aspirin and thienopyridine are associated with gastrointestinal (GI) complications such as petechiae, erosion, ulcer, bleeding, and perforation. The incidence of GI bleeding in aspirin study groups was 0.82 % in the hypertension optimal treatment (HOT) study and 0.76 % in the primary prevention project (PPP) study. On the other hand, the incidence of GI bleeding by endoscopic evaluation was higher than in an observational study. In a study of 187 patients receiving low-dose aspirin for prevention of cardiovascular disease, the prevalence of endoscopically detected GI ulcers was 11 % (95 % CI 6.3-15.1 %). Several risk factors for GI bleeding (history of peptic ulcer or GI bleeding, high aspirin dose, concomitant use of non-steroidal anti-inflammatory drugs and anti-platelet agents, advanced age and Helicobacter pylori infection) were reported for patients receiving aspirin. Prevention strategies for GI complications induced by anti-platelet agents are treatment with proton pump inhibitors, histamine-2 receptor antagonists, prostaglandin analogs, prostaglandin inducers and H. pylori eradication therapy. Further investigation is necessary to identify the strategies which are suitable for Japan.

Evaluation of basophil CD203c as a predictor of carboplatin-related hypersensitivity reaction in patients with gynecologic cancer.

The incidence of hypersensitivity reaction (HR) to carboplatin has been reported to increase after repeated use of the drug. However, a reliable ex vivo test to predict HR to carboplatin is not currently available. We evaluated the clinical usefulness of measuring basophil CD203c to predict carboplatin-related HR in this prospective case-control study conducted at Mie University Hospital between October 2009 and September 2010. Eleven patients had history of carboplatin-related HR within the past 3 years, and 19 had no history of HR after receiving more than 5 courses of carboplatin therapy. Six of these 19 patients developed carboplatin-related HR during the study period. The CD203c+ basophils (%) and the mean fluorescence intensity (MFI) were analyzed on a flow cytometer and compared between patients with and without HR. Changes in the CD203c expression on basophils before and after HR were also assessed in patients who developed HR during the study period. The median CD203c+ basophils (%) and ΔMFI after 30-min exposure to 50 µg/mL carboplatin were significantly higher in patients with HR (3.5% and ΔMFI 9.0) compared with those without (2.2% and ΔMFI 0.4) (p<0.05). In particular, these values were significantly higher in patients with grade 4 anaphylaxis (10.6% and ΔMFI 22.0). All five patients who developed grade 2-4 anaphylaxis during the study period had high CD203c+ basophils (%) and/or increased ΔMFI on the day before HR. The results suggest that basophil CD203c may be a promising biomarker for the prediction of severe carboplatin-related anaphylaxis.

[A case of pseudomembranous colitis concomitant with toxic megacolon and paralytic ileus].

A 60-year-old man was diagnosed as pseudomembranous colitis with chief complaint of fever and abdominal distension after a cerebral operation. It was ineffective although vancomycin hydrochloride (VCM) was given orally. Complications occurred. The patient had toxic megacolon and paralytic ileus. VCM was administrated via an ileus tube. In addition, the bowel was lavaged and VCM was sprayed by colonoscopy. This therapy was very effective. Generally, a patient with pseudomembranous colitis concomitant with toxic megacolon or/and paralytic ileus is considered to have a poor prognosis, however, he completely recovered by a combination of medical treatment.

Risk factors contributing to the development of carboplatin-related delayed hypersensitivity reactions in Japanese patients with gynecologic cancers.

PURPOSE: The rate of hypersensitivity reactions in patients receiving carboplatin (CBDCA) has been reported to increase after multiple doses of the agent. However, risk factors for these onsets have not been well described. In this study, we investigated the contribution of the reported risk factors to the onset of CBDCA-related delayed hypersensitivity reactions. METHODS: We reviewed the records of gynecologic cancer patients receiving CBDCA of more than 7 cycles in Mie University Hospital from March 2006 to July 2009. The patients were divided into two groups on the basis of whether hypersensitivity reactions developed (13 patients) or not (43 patients). Thereafter, the potential influences of the patients' characteristics on the development of CBDCA-related delayed hypersensitivity reactions were explored using logistic regression analyses. RESULTS: The median CBDCA-free interval (10 months) in patients with hypersensitivity reactions was significantly higher than that (3 months) in patients without hypersensitivity reactions. Logistic regression analyses revealed a CBDCA-free interval >13 months (odds ratio 22.2, 95% confidence interval 2.57-192, p < 0.01) and a maximum dose of CBDCA > 650 mg (odds ratio 9.52, 95% confidence interval 1.04-93.9; p < 0.05) were significantly correlated with the incidence of CBDCA-related delayed hypersensitivity reactions. CONCLUSIONS: Careful attention should be paid to the onset of delayed hypersensitivity reactions for recurrent gynecologic cancer patients receiving CBDCA > 650 mg after an interval of more than 13 months from the previous CBDCA administration.

Clinical evaluation of emergency endoscopic hemostasis with bipolar forceps in non-variceal upper gastrointestinal bleeding.

The present study was designed to evaluate the usefulness and safety of bipolar hemostatic forceps, known as a less invasive and highly safe means of thermal coagulation used for hemostasis in cases of non-variceal upper gastrointestinal bleeding. This technique of bipolar forceps is simple, safe and unlikely to induce complications, and is therefore promising as a new technique of endoscopic hemostasis. The study involved 39 cases where hemostasis was attempted with bipolar forceps to deal with non-variceal upper gastrointestinal bleeding, including 28 cases of gastric ulcer, six cases of duodenal ulcer, three cases of bleeding after endoscopic submucosal dissection (ESD), one case of Mallory-Weiss syndrome and one case of postoperative bleeding from the anastomosed area. There were 34 males and five females, with a mean age of 63.6 years. Bipolar forceps were the first-line means of hemostasis in cases of oozing bleeding (venous bleeding), pulsatile or spurting bleeding (arterial bleeding) and exposed vessels without active bleeding. The primary hemostasis success rate was 92.3%, and the re-bleeding rate was 0%. In cases where the bleeding site was located along the tangential line or in cases where large respiration-caused motions hampered identification of the bleeding site, hemostasis by means of coagulation was easily effected by application of electricity while the forceps were kept open and compressed the bleeding area. In addition, there were no complications. This technique of bipolar forceps is simple, safe and unlikely to induce complications, and is therefore promising as a new technique of endoscopic hemostasis.