Range of Motion of the Temporomandibular Joint in Rheumatoid Arthritis: Relationship to the Severity of Disease

The purpose of this study was to determine the frequency and nature of temporomandibular joint (TMJ) involvement in rheumatoid arthritis (RA) patients with symptoms in this joint, and to investigate the relationship of symptoms to the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and Steinbrocker stage. Clinical examination of the range of motion of the TMJ was performed in 218 RA patients. In addition, correlations between the maximal mouth opening and the severity of RA were studied. Restriction in opening the mouth (defined as ≤ 30 mm movement in the central incisor region from the fully occluded to maximally open positions) was observed in 12.8% of the RA patients (28/218). The CRP, ESR and Steinbrocker stage were all correlated with maximal opening (p < 0.05). There was a positive correlation between the severity of RA and the range of motion of the jaw.     

Pancreatic Islet Vasculature Adapts to Insulin Resistance Through Dilation and Not Angiogenesis

Pancreatic islets adapt to insulin resistance through a complex set of changes, including β-cell hyperplasia and hypertrophy. To determine if islet vascularization changes in response to insulin resistance, we investigated three independent models of insulin resistance: ob/ob, GLUT4^+/−, and mice with high-fat diet–induced obesity. Intravital blood vessel labeling and immunocytochemistry revealed a vascular plasticity in which islet vessel area was significantly increased, but intraislet vessel density was decreased as the result of insulin resistance. These vascular changes were independent of islet size and were only observed within the β-cell core but not in the islet periphery. Intraislet endothelial cell fenestration, proliferation, and islet angiogenic factor/receptor expression were unchanged in insulin-resistant compared with control mice, indicating that islet capillary expansion is mediated by dilation of preexisting vessels and not by angiogenesis. We propose that the islet capillary dilation is modulated by endothelial nitric oxide synthase via complementary signals derived from β-cells, parasympathetic nerves, and increased islet blood flow. These compensatory changes in islet vascularization may influence whether β-cells can adequately respond to insulin resistance and prevent the development of diabetes.Pancreatic islets are highly vascularized, and this feature is critical for β-cells to rapidly sense the blood glucose and secrete insulin into the systemic circulation (1,2). Islet vascularization begins early in pancreas development and is maintained in adulthood as a consequence of islet cell production of angiogenic factors such as vascular endothelial growth factor-A (VEGF-A) and angiopoietin-1 (Ang-1) (3–6). These factors recruit endothelial cells (ECs), stimulate blood vessel growth and maturation, and in the case of VEGF-A, promote formation of EC fenestrations (5,6). In addition, ECs adjacent to pancreatic epithelium reciprocally influence islet cell differentiation and development (7,8).β-Cells have a remarkable ability to respond to changes in an organism’s metabolic state, such as changes in the blood glucose or increased insulin requirements. For example, when insulin resistance develops, β-cells of the pancreatic islet can dramatically increase insulin production and secretion with an increase of β-cell mass, thus maintaining normoglycemia (9,10). In this way, mouse models with marked insulin resistance and humans with obesity-related insulin resistance are hyperinsulinemic but not hyperglycemic. The mechanisms underlying this β-cell adaptation to insulin resistance and their subsequent failure in some individuals who develop type 2 diabetes are incompletely understood.Because of the highly vascularized state of pancreatic islets and the marked changes in β-cell size and number in the setting of insulin resistance, we hypothesized that the islet vasculature must adapt to these changes in β-cell mass and insulin requirements. We envisioned that a hyperplastic islet, like a growing tumor mass, would increase production of angiogenic factors to increase its vascular supply with expanding β-cell mass (11). To test this hypothesis, we examined islet vascularization in three mouse models of insulin resistance and found, unexpectedly, that islet vessel density was decreased, not increased, and that the intraislet vasculature became markedly dilated whereas vessels in the exocrine tissue were unchanged. The dilation of intraislet capillaries was independent of islet size, suggesting the vascular adaptation may primarily support increased β-cell insulin secretory demand rather than β-cell mass expansion. Moreover, these vascular changes were accompanied by an increase in islet parasympathetic innervation. Our results indicate that the metabolic state influences islet angioarchitecture and innervation, suggesting that islet neurovascular remodeling may influence whether β-cells can adequately respond to insulin resistance and maintain normoglycemia.     

Processed blood volume impacts clinical efficacy in patients with ulcerative colitis undergoing adsorptive depletion of myeloid lineage leucocytes

Background  

Hitherto, therapeutic depletion of granulocytes and monocytes by adsorption (GMA) has been associated with significant and insignificant efficacy in patients with ulcerative colitis (UC). Further, the processed blood volume in one GMA session has been fixed at 30 mL/min × 60 min, regardless of patients’ body weight (BW). We were interested to see the efficacy and safety of GMA when administered in relation to patients’ BW.     

Transdermal tulobuterol patch, a long-actingβ(2)-agonist

Tulobuterol patch (HokunalinTM Tape), which contains a β(2)-adrenergic agonist, is the first bronchodilator to be available as a transdermal patch. This drug delivery system ensures that the time at which the peak drug concentration in the blood is reached coincides with the morning dip in respiratory function. The use of the patch also prevents excessive increase in blood drug concentrations, thereby reducing the incidence of systemic adverse reactions. Since 1998, when it was first approved in Japan and worldwide, the tulobuterol patch has been used widely in the treatment of bronchial asthma and chronic obstructive pulmonary disease (COPD), and evidence collected since it was approved has confirmed its clinical efficacy and safety. Because the patch is easy to use and requires only once-daily application, treatment adherence of patients using the patch is good. In this article, we discuss the rationale behind the development of the tulobuterol patch, evaluate data on its clinical efficacy and safety in the treatment of asthma and COPD, and examine the treatment adherence in individuals using the patch.     

Efficacy and safety of indacaterol 150 and 300 µg in chronic obstructive pulmonary disease patients from six Asian areas including Japan: a 12-week, placebo-controlled study

Background and objective: The efficacy and safety of indacaterol, a novel inhaled once daily ultra long‐acting β₂‐agonist was evaluated in COPD patients in six Asian countries/areas. This study was primarily designed to obtain the regulatory approval of indacaterol in Japan. Methods: Moderate‐to‐severe COPD patients were randomized to indacaterol 150 µg, indacaterol 300 µg or placebo once daily. Efficacy variables: trough FEV₁ (average of 23 h 10 min and 23 h 45 min post‐dose values), health status (St. George's Respiratory Questionnaire) and transition dyspnoea index at week 12. Safety/tolerability was evaluated. Results: A total of 347 patients were randomized (96.5% male, mean (SD) age 66.7 (8.38) years, post‐bronchodilator FEV₁% predicted: 53.7 (12.50)); 88.8% completed. The least squares means (LSM) trough FEV₁ at week 12 for indacaterol 150 µg, indacaterol 300 µg and placebo were 1.34 L, 1.37 L and 1.17 L, respectively, with differences versus placebo exceeding the prespecified minimal clinically important difference of 0.12 L (0.17 L and 0.20 L for indacaterol 150 µg and 300 µg, respectively, both P < 0.001). The week 12 LSM transition dyspnoea index score was statistically superior for both indacaterol doses versus placebo (differences of 1.30 and 1.26, P < 0.001; both exceeding the minimal clinically important difference of 1). At week 12, both indacaterol doses provided statistically significant (P ≤ 0.005) and clinically meaningful (≥4 units) improvements in LSM St. George's Respiratory Questionnaire total score versus placebo (differences: ?4.8 and ?5.7 units). Adverse events for indacaterol (49.1%, both doses) were lower than placebo (59.0%) and were mostly mild/moderate in severity; no deaths were reported. Conclusions: Indacaterol provided clinically significant bronchodilation and improvements in dyspnoea and health status in Asian COPD patients.     

A case of adult-onset Still's disease (AOSD)-like manifestations abruptly developing during confirmation of a diagnosis of metastatic papillary thyroid carcinoma

A 68-year-old Japanese man was admitted to our hospital suffering from abrupt onset of high fever accompanied by arthralgia, myalgia, sore throat, macular eruption, and liver dysfunction. Six months before the onset of these manifestations, (18)F-fluoro-deoxy-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) had detected, unexpectedly, three calcified thyroid lesions without (18)F-FDG uptake. Two months before the onset of the present manifestations, ultrasonography-guided fine-needle aspiration had led to a diagnosis of papillary thyroid carcinoma (PTC). Soon after the occurrence of the rheumatic manifestations, a subsequent (18)F-FDG PET/CT scan showed not only the three thyroid lesions, the same as those in the previous scan, but also (18)F-FDG uptake in the thyroid lesion. A diagnosis of adult-onset Still's disease (AOSD)-like manifestations associated with PTC was made, and treatment with 40?mg/day of prednisolone (PSL) resolved the symptoms promptly. PSL was gradually tapered, without recurrence of the (AOSD)-like manifestations. Five months after the initiation of treatment with PSL, total thyroidectomy, followed by (131)I thyroid ablation treatment, was performed while the patient was on a PSL dose of 18?mg/day. Seven months after the thyroidectomy, the dose of PSL was tapered to 2?mg/day, and neither the AOSD-like manifestations nor the PTC relapsed. On confirming a diagnosis of AOSD, it may be necessary to consider the presence of an associated malignancy, including solid tumors such as PTC.     

SPan-1 Is a Useful Prognostic Marker for Patients with Stage IV Gastric Cancer Who Underwent Palliative Gastrectomy: A Retrospective Multivariate Study

Background

We retrospectively investigated prognostic factors to be used in selecting the patients with stage IV gastric cancer (GC) who have an unfavorable prognosis after palliative gastrectomy.

Methods

A total of 146 GC patients at stage IV who had undergone palliative gastrectomy were enrolled. Various clinicopathological parameters were evaluated for prognosis.

Results

Surgical morbidity and hospital mortality occurred in 35 (23.9 %) and 4 (2.7 %) patients, respectively. The overall 5-year survival rate and the median survival time were 11.2 % and 13.2 months, respectively. Of the 146 patients, 64 had uncomfortable symptoms associated with GC and 76 had no such symptoms. Of the 64 patients with uncomfortable symptoms, 60 (93.7 %) experienced relief of these symptoms after palliative surgery. Multivariate analysis for patients without uncomfortable symptoms associated with GC revealed that the number of incurable factors and serum SPan-1 level were independent prognostic factors.

Conclusions

Patients with stage IV GC who had multiple incurable factors and a high level of serum SPan-1 might not be candidates for palliative gastrectomy for the purpose of prognostic benefit.     

Effects of uncomplicated carotid endarterectomy on cognitive function and brain perfusion in patients with unilateral asymptomatic severe stenosis of the internal carotid artery by comparison with unoperated patients

Objective: The purpose of the present exploratory study was to evaluate the effects of uncomplicated carotid endarterectomy (CEA) on cognitive function and brain perfusion in patients with unilateral asymptomatic severe stenosis of the internal carotid artery (ICA) by comparison with unoperated patients.

Methods: Patients with age ≤75 years and unilateral asymptomatic severe stenosis (≥70%) of the cervical ICA underwent CEA with antiplatelet therapy (surgically treated group: 116 patients) or antiplatelet therapy alone or neither (medically treated group: 45 patients). For the surgically treated group, neuropsychological testing and brain perfusion measurement using single-photon emission computed tomography were performed within one month before surgery and one month after surgery. For the medically treated group, the same testing and measurement were performed twice at an interval of 1 to 2 months.

Results: None of the operated patients developed new major ischemic events after surgery or intraoperative cerebral hyperperfusion. None of the patients in the medically treated group experienced neurological deficits including transient ischemic attacks during the study period. The incidence of patients with interval cognitive improvement was significantly greater in the surgically treated group (11 patients: 9%) than in the medically treated group (0%) (p = 0.0352). The incidence of patients with interval brain perfusion improvement in the ipsilateral cerebral hemisphere was significantly greater in the surgically treated group (24 patients: 21%) than in the medically treated group (0%) (p = 0.0003).

Conclusions: Uncomplicated CEA may improve cognitive function and brain perfusion in patients with unilateral asymptomatic severe stenosis of the ICA when compared with unoperated patients.