Survey on changes in subjective symptoms,onset/trigger factors,allergic diseases,and chemical exposures in the past decade of Japanese patients with multiple chemical sensitivity

Background

Recently, with rapid changes in the Japanese lifestyle, the clinical condition of patients with multiple chemical sensitivity (MCS) may also have undergone change. Thus, we conducted a new survey for subjective symptoms, ongoing chemical exposures, the prevalence of allergic diseases, and presumed onset/trigger factors in patients with MCS and compared results with those of an old survey from ten years ago.

Acid profile in carious dentin

Organic acids in carious dentin from 69 permanent teeth were analyzed by gas chromatography. Lactate, acetate, propionate, and butyrate were detected in most samples, and limited amounts of isobutyrate, valerate, isovalerate, caproate, and isocaproate were occasionally detected. Lactate, acetate, and propionate were major acids and altogether accounted for about 90% of total acid in most samples of carious dentin. However, the proportion of these three acids varied among the samples. Some samples contained over 85% lactate, while others contained mainly acetate and propionate. A high percentage of acetate was usually accompanied by an appreciable amount of propionate. All seven samples in carious dentin under fillings or restorations had little lactate, but a high percentage of acetate plus propionate. The differences in acid profiles of carious dentin may reflect differences in the microbial ecology of carious dentin, and a stage of progress of dentin caries or a type of dentin caries.     

Phase 1 study of tazemetostat in Japanese patients with relapsed or refractory B-cell lymphoma

BackgroundTazemetostat is a selective and orally available inhibitor of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and epigenetic regulator of cellular differentiation programs. We carried out a phase I study of tazemetostat in Japanese patients with relapsed or refractory B‐cell non‐Hodgkin‐type lymphoma (B‐NHL) to evaluate its tolerability, safety, pharmacokinetics, and preliminary antitumor activity.MethodsTazemetostat was given orally at a single dose of 800 mg on the first day and 800 mg twice daily (BID: total 1600 mg/d) on following days in a 28‐day/cycle manner. Tazemetostat dose‐limiting toxicity (DLT) was evaluated up to the end of the first treatment cycle. Archival tumor tissues were analyzed for hotspot EZH2 mutations.ResultsAs of 15 January 2018, seven patients (four follicular lymphoma [FL] and three diffuse large B‐cell lymphoma [DLBCL]) were enrolled. The median age was 73 (range, 59‐85) years, and the median number of prior chemotherapy regimens was three (range, one to five). No DLT was observed (one patient was not evaluable due to early disease progression). The common treatment‐related adverse events (AEs) were thrombocytopenia and dysgeusia (three patients each; 42.9%). No treatment‐related serious AEs were observed. The objective response rate was 57% (4/7 patients), including responses in three of four patients with FL and one of three patients with DLBCL. An EZH2 mutation was detected in one patient with FL responding to treatment.ConclusionsTazemetostat at 800 mg BID showed an acceptable safety profile and promising antitumor activity in Japanese patients with relapsed or refractory B‐NHL.     

Histological sequence of the development of rat mesothelioma by MWCNT,with the involvement of apolipoproteins

A rat model of mesothelioma development by peritoneal injection of multiwalled carbon nanotube (MWCNT) has been established and found to be useful to understand the mechanisms underlying fibrous particles-associated carcinogenesis. Its detailed histological sequence, however, remains largely obscure. We therefore aimed to assess the time-course of mesothelioma development by MWCNT and evaluate a set of lipoprotein-related molecules as potential mechanism-based biomarkers for the phenomenon. Male Fischer 344 rats were injected intraperitoneally (ip) with MWCNT (MWNT-7) at 1 mg/kg body weight, and necropsied at 8, 16, 24, 32, or 42 wk after injection. For biochemical analyses of the lipoprotein-related molecules, more samples, including severe mesothelioma cases, were obtained from 2 other carcinogenicity tests. Histologically, in association with chronic inflammation, mesothelial proliferative lesions appeared at c. Wk-24. Before and at the beginning of the tumor development, a prominent infiltration of CD163-positive cells was seen near mesothelial cells. The histological pattern of early mesothelioma was not a papillary structure, but was a characteristic structure with a spherical appearance, composed of the mesothelioma cells in the surface area that were underlain by connective tissue-like cells. Along with the progression, mesotheliomas started to show versatile histological subtypes. Serum levels of apolipoprotein A-I and A-IV, and a ratio of HDL cholesterol to total cholesterol were inversely correlated with mesothelioma severity. Overall, the detailed histological sequence of mesotheliomagenesis by MWCNT is demonstrated, and indicated that the altered profile of apolipoproteins may be involved in its underlying mechanisms.     

GERD and tight junction proteins of the esophageal mucosa

Recent advancement in the research of GERD has revealed that endoscopy negative GERD may not be a milder form of erosive GERD and may have different pathogenesis. We have previously proven that hypersensitivity to the acid of the esophageal mucosa plays an important role in its pathogenesis. Regarding the mechanisms for the esophageal hypersensitivity, we hypothesized that the tight junction proteins of the esophageal mucosa are fully or partially impaired in GERD patients. Accordingly, we immunohistologically studied the expression of various tight junction proteins using the rat reflux esophagitis model. The results demonstrated that the several kinds of tight junction proteins are expressed differently in the various parts of esophagus and their expression altered according to the development of reflux esophagitis.     

Acute Pancreatitis and Cholecystitis Associated with Postpartum HELLP Syndrome: A Case and Review

We report a case of preeclampsia associated with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome and concomitant nonbiliary acute pancreatitis and cholecystitis in the first postpartum day. A thorough investigation ruled out known etiologies of both pancreatitis and cholecystitis. Following conservative treatment, the patient's HELLP syndrome, pancreatitis, and cholecystitis resolved on the third postpartum day. Preeclampsia is associated with microvascular abnormalities that may involve the splanchnic circulation. These abnormalities may cause not only HELLP syndrome but also pancreatitis and cholecystitis. Recognizing that ischemia can damage not only the liver but also the pancreas and gallbladder, could result in improvements in the diagnosis and management of pancreatitis in patients with preeclampsia.     

Transcatheter closure of secundum atrial septal defect

Since the introduction of transcatheter closure of atrial septal defect, device closure has become the alternative treatment of selected atrial defects. Although excellent results have been reported for transcatheter closure, concerns have arisen regarding complications, including residual shunt, systemic or pulmonary embolization of the device, and erosion and perforation of the cardiac chamber. Those complications are rare but potentially serious adverse events that may require immediate surgical intervention. This review summarizes the current trends in patient selection, result of device closure and typical complications. Comparison between transcatheter device closure and surgical closure is also made.