Treatment of idiopathic gustatory rhinorrhea by resection of the posterior nasal nerve

We herein describe a case of 44-year old female who presented with a chief complaint of gustatory rhinorrhea from childhood, in which gustatory stimuli caused bilateral excessive, watery nasal secretion. No abnormality of taste acuity was observed. This disorder was presumably caused by faulty regenerated parasympathetic nerve fibers reaching the nasal mucosa or possibly, by a congenital condition. Nasal pretreatment with an anti-cholinergic drug clinically blocked the positive sugar-induced rhinorrhea, thus indicating that the gustatory rhinitis in this case was produced by foods that stimulate muscarinic receptors sensitive to atropine (probably on submucosal nasal glands). Although this syndrome can be treated prophylactically by the use of topical atropine, the patient preferred to undergo radical therapy and a resection of the posterior nasal nerve was performed through the middle meatus under endoscopic control. The resection of the nerve on both sides resulted in an almost complete inhibition of the sugar-induced rhinorrhea without serious complications. Although this disease is not life-threatening, it is socially embarrassing and troublesome to patients and surgical therapy is one of the accepted modalities.     

α2-Antiplasmin Is Associated with the Progression of Fibrosis

Systemic sclerosis results in tissue fibrosis due to the activation of fibroblasts and the ensuing overproduction of the extracellular matrix. We previously reported that the absence of α2-antiplasmin (α2AP) attenuated the process of dermal fibrosis; however, the detailed mechanism of how α2AP affects the progression of fibrosis remained unclear. The goal of the present study was to examine the role of α2AP in fibrotic change. We observed significantly higher levels of α2AP expression in the skin of bleomycin-injected systemic sclerosis model mice in comparison with the levels seen in control mice. We also demonstrated that α2AP induced myofibroblast differentiation, and the absence of α2AP attenuated the induction of myofibroblast differentiation. Moreover, we found that connective tissue growth factor induced the expression of α2AP through both the extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways in fibroblasts. Interestingly, α2AP also induced transforming growth factor-β expression through the same pathways, and the inhibition of ERK1/2 and JNK slowed the progression of bleomycin-induced fibrosis. Our findings suggest that α2AP is associated with the progression of fibrosis, and regulation of α2AP expression by the ERK1/2 and JNK pathways may be an effective antifibrotic therapy for the treatment of systemic sclerosis.Systemic sclerosis (SSc) affects the skin and the internal organs, resulting in tissue fibrosis. Although the disease process involves immunological mechanisms, vascular damage, and activation of fibroblasts, the pathogenesis of SSc remains to be further elucidated. Fibrotic diseases are characterized by excessive scarring due to excessive production, deposition, and contraction of the extracellular matrix (ECM). This process usually occurs over many months and years, and can lead to organ dysfunction or death. Connective tissue growth factor (CTGF) is constitutively overexpressed in fibrotic lesions such as in scleroderma,¹ liver,² renal,^3,4 lung,⁵ and pancreatic fibrosis.⁵ CTGF acts as a downstream effecter of at least some of the profibrotic effects of transforming growth factor-β (TGF-ß),⁶ and promotes fibroblast proliferation, myofibroblasts differentiation, matrix production, and granulation tissue formation.^7,8Human and murine α2-antiplasmin (α2AP) are serpins (serine protease inhibitors) with a molecular weight of 65 to 70 kd,⁹ which rapidly inactivate plasmin, resulting in the formation of a stable inactive complex, plasmin-α2AP.¹⁰ Tissue fibrosis is generally considered to arise due to a failure of the normal wound healing response to terminate.¹¹ Previous our studies show that α2AP is associated with the wound healing and the fibrosis.^12,13 In addition, it has been reported that the level of plasmin-α2AP complex in plasma is elevated in SSc patients.¹⁴ These findings suggest that α2AP may be associated with the progression of fibrotic disease, but the physiological roles of α2AP are not precisely understood. We herein report that α2AP plays an important role in the progression of fibrosis.     

Dysuria therapeutic agents as an independent prognostic factor for the primary recurrence of non-muscle invasive bladder cancer: a propensity score matching study

ObjectiveTo investigate if the use of therapeutic agents for dysuria is a risk factor for the primary recurrence of non-muscle invasive bladder cancer (NMIBC).MethodsFirst, patients with NMIBC were divided into two groups: the non-recurrence group and the recurrence group. Patient characteristics were compared between both groups. The risk factors of recurrence that were statistically different between the two groups were identified by multivariate analysis. Second, we divided the patients into risk and non-risk groups, and differences in the recurrence-free survival (RFS) between the two groups were analyzed before and after propensity score matching (PSM).ResultsA total of 162 patients were included, with 84 patients in the non-recurrence group and 78 patients in the recurrence group. In the multivariate analysis, the intake of dysuria agents and bacillus Calmette–Guérin (BCG) therapy were independent factors. The RFS results in terms of the intake of dysuria agents were statistically significant before and after PSM analysis, but no factors were significantly different between the BCG and non-BCG groups after PSM.ConclusionsTherapeutic agents for dysuria might be at an independent risk factor for NMIBC recurrence. This trial is registered with the UMIN Clinical Trials Registry under the number UMIN000036097 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno = R000041122).     

Clinical course of patients with aplastic anemia or myelodysplastic syndrome associated with persistent neutropenia

Patients with aplastic anemia (AA) or myelodysplastic syndrome (MDS) often have persistent severe neutropenia and are susceptible to infectious complications. We retrospectively reviewed the clinical course of patients with AA or MDS who had neutropenia (neutrophil count < 500/μl) for more than 25 days. A total of 46 patients, 11 with AA and 35 with MDS, were included. Twenty-three patients had infectious events (IE), and the cumulative incidence of IE was 30% at 6 months and 51% at 1 year. The cumulative incidence of IE was 67% at 1 year in 30 patients who experienced very severe neutropenia of less than 200/μl. Overall survival in all patients was 76% at 6 months and 65% at 1 year. In a multivariate analysis, male sex, underlying diseases, and a neutrophil count of less than 200/μl as a time-dependent covariate significantly affected IE. In analyses that excluded patients with AA, male sex was the only factor. In conclusion, severe neutropenia was significantly associated with IE in patients with AA or MDS, and IE might be lethal. When we only considered patients with MDS, the neutrophil count alone could not be used to predict the prognosis.     

Hypoglycemic effect of hot-water extract of adzuki (Vigna angularis) in spontaneously diabetic KK-A(y) mice

ObjectiveRecently, we reported that 40% ethanol fraction of hot-water extracts of adzuki (Vigna angularis; EtEx.40) suppressed the postprandial blood glucose level and serum insulin level in normal mice and streptozotocin-induced type 1 diabetic rats. The present study examined the hypoglycemic effect of EtEx.40 on blood glucose, insulin concentrations, organ weight, serum composition, and hepatic lipid content in spontaneously diabetic KK-A^y/Ta Jcl mice, a model for type 2 diabetes.MethodsTo investigate the prevention of type 2 diabetes by EtEx.40 ingestion, 4-wk-old non-diabetic KK-A^y mice were fed an AIN-76 diet containing 5000 mg of EtEx.40/kg of body weight per day (EtEx.40) or an AIN-76 diet without EtEx.40 for 8 wk. Furthermore, to investigate the improvement of type 2 diabetes, 7-wk-old diabetic KK-A^y mice were fed EtEx.40 for 4 wk.ResultsCompared with the control group, EtEx.40 supplementation had a significant effect in lowering blood glucose levels, water intake, serum insulin levels, urinary glucose, urinary microalbumin/creatinine ratio, liver triacylglycerol, and total cholesterol levels. Similar results were observed in 7-wk-old diabetic KK-A^y mice fed EtEx.40 for 4 wk. These effects were also found after short-term administration of EtEx40. Overall, EtEx.40 improved several diabetic symptoms in KK-A^y mice.ConclusionEtEx.40 obtained from hot-water adzuki extracts showed preventive and ameliorative effects on the progression of diabetes in genetically diabetic KK-A^y mice. In the present study, we conclude that the preventive and ameliorative effects by EtEx.40 were due to the modulation of blood glucose levels and the protective effect against oxidative damage in diabetes mellitus.     

Increased synthesis of indoleamine-2,3-dioxygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer

We previously reported that indoleamine-2,3-dioxygenase (IDO) is associated with paclitaxel resistance and that IDO serves as a marker of poor prognosis in ovarian serous adenocarcinomas (SA). In this study, to explore the role of IDO in the development of various histological types of ovarian cancer, we further examined IDO expression not only in SA but also in other types of ovarian cancers. Expression of IDO protein was analyzed by immunohistochemistry for a total of 122 ovarian cancers including 40 SA, 67 clear cell adenocarcinomas (CCA), and 15 endometrioid adenocarcinomas (EA) with informed consent. Among these cases, there were 11 CCA accompanied with endometriosis and 60 cases with lymph node metastasis. We classified the samples into four categories by IDO staining pattern. IDO staining was positive in 57.5% of SA, 49.2% of CCA, and 73.3% of EA, respectively. The Kaplan-Meier survival curve showed a clear relationship between staining score and overall survival for patients with advanced (stages III and IV) SA (n=33) who underwent optimal surgery and paclitaxel-carboplatin (TC) chemotherapy as a first-line regimen. There was no association between IDO staining score and overall survival in the CCA cases. Eight of 11 cases (72.7%) of CCA accompanied by endometriosis presented identical staining patterns of IDO between CCA and endometriosis. In 43 of 60 cases (71.6%) with lymph node metastasis, the staining patterns of IDO showed a correspondence between the primary lesion and metastatic site. These results suggested that the increased synthesis of IDO protein was positively associated with impaired survival only in the serous type of ovarian cancer.     

Metal patch testing in patients with oral symptoms

The number of patients with metal allergies has increased recently, and patch testing is useful for investigating such patients. However, the efficacy of restoration removal in patients with oral metal allergies is disputed. This study aimed to investigate the relationships between oral symptoms and metal allergies. We conducted a retrospective analysis of 60 patients with oral symptoms. The most common oral symptom was an abnormal oral sensation. Thirty‐eight percent of the patients exhibited positive allergic reactions to one or more metal. Nickel was the metal allergen that produced positive reactions most frequently. Of the seven patients whose restorations were removed, complete and partial remission were achieved in one and two patients, respectively. Interestingly, metal alloy removal was effective in 33% (n = 1) of the positive patch test group and 50% (n = 2) of the non‐positive patch test group. Our results demonstrated the difficulty of predicting the efficacy of restoration removal at ameliorating oral metal allergies based on patch testing alone.     

Development of a functional wound dressing composed of hyaluronic acid spongy sheet containing bioactive components: evaluation of wound healing potential in animal tests

This study aimed to develop a novel wound dressing composed of hyaluronic acid (HA) spongy sheet containing bioactive components. The wound dressing prepared by the freeze-drying method has a two-layered structure: an upper layer composed of cross-linked high-molecular-weight HA (HMW-HA) and a lower layer composed of low-molecular-weight HA (LMW-HA) containing arginine (Arg), magnesium ascorbyl phosphate (vitamin C derivative: VC), and epidermal growth factor (EGF) (referred to as EGF-dressing). A wound dressing containing only Arg and VC was prepared in a similar manner (referred to as EGF-free-dressing). The potential of each wound dressing was evaluated in animal tests using Sprague Dawley (SD) rats and diabetic mice. In the first experiment, each wound dressing was applied to a full-thickness skin defect in the abdominal region of SD rats. Wound conditions after 1?week and 2?weeks of treatment were evaluated based on macroscopic and histological appearance. A commercially available non-woven alginate wound dressing (Alg-dressing) was used in a control group. Both EGF-free-dressing and EGF-dressing decreased wound size and promoted granulation tissue formation associated with angiogenesis more effectively when compared with Alg-dressing. In particular, EGF-dressing promoted re-epithelialization. In the second experiment, each wound dressing was applied to a full-thickness skin defect in the dorsal region of diabetic mice. Wound conditions after 1?week and 2?weeks of treatment were evaluated based on macroscopic and histological appearance. A commercially available Alg-dressing was used in a control group. Both EGF-free-dressing and EGF-dressing decreased wound size and promoted granulation tissue formation associated with angiogenesis more effectively when compared with Alg-dressing. These findings indicate that EGF-free-dressing and EGF-dressing have the potential for more effective wound healing when compared with Alg-dressing. In particular, EGF-dressing has a higher potential for wound healing when compared with EGF-free-dressing.     

Delayed platelet recovery after allogeneic hematopoietic stem cell transplantation: Association with chronic graft‐versus‐host disease and survival outcome

Delayed platelet recovery (DPR) despite prompt neutrophil engraftment is frequently observed after allogeneic hematopoietic stem cell transplantation (HSCT). However, few studies have evaluated the risk factors and long‐term outcome. Therefore, we retrospectively analysed 219 adult patients who underwent their first allogenic HSCT with neutrophil engraftment. Of these 219 patients, 50 (22.8%) had DPR that was defined as relapse‐free survival at day 60 after HSCT without primary platelet recovery despite neutrophil engraftment. The results of a multivariate analysis showed that a high‐risk underlying disease (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.04‐5.48; P = .041) and human leukocyte antigen–mismatched HSCT (OR, 2.63; 95% CI, 1.28‐5.43; P = .009) were associated with an increased risk of DPR. In univariate analyses, the occurrence of DPR was significantly associated with inferior overall survival, high nonrelapse mortality, and a low incidence of chronic graft‐versus‐host disease (GVHD), despite a comparable relapse rate. In multivariate analyses, DPR was associated with inferior overall survival (hazard ratio [HR], 2.00; 95% CI, 1.23‐3.27; P = .005) and a low incidence of chronic GVHD (HR, 0.42; 95% CI, 0.22‐0.78; P = .002). In conclusion, DPR was a strong predictor of shorter survival but also less frequent chronic GVHD.