Esophageal motor dysfunction plays a key role in GERD with globus sensation - Analysis of factors promoting resistance to PPI therapy

Abstract Objective. Patients with gastroesophageal reflux disease (GERD) also have various extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy achieves disappointing results. This study investigated esophageal motility in GERD patients with globus sensation who were resistant to PPI therapy. Design. The subjects were 350 patients with globus sensation. All patients underwent both laryngoscopy and upper gastrointestinal endoscopy to exclude organic disease. After 4 weeks of treatment with rabeprazole sodium (20 mg daily), the patients were divided into PPI-responsive and PPI-resistant groups. Then we investigated esophageal motility in the PPI-resistant group by a multichannel intraluminal impedance and manometry study. Results. A total of 119 patients (55.6%) were resistant to PPI therapy, among whom 57 patients (47.9%) had abnormal esophageal motility. They included 36 patients (66.4%) with ineffective esophageal motility, 9 patients (14.4%) with achalasia, 6 patients (9.6%) with diffuse esophageal spasm, 5 patients (8%) with nutcracker esophagus, and 1 patient (1.6%) with hypertensive lower esophageal sphincter. There were significant differences of upper esophageal sphincter pressure and esophageal body peristalsis between the patients with PPI-resistant LPRD and healthy controls matched for age and sex. Conclusion. Among patients with PPI-resistant LPRD, 47.9% had abnormal esophageal motility.     

Age-related changes in the thickness of the deep and superficial abdominal muscles in women

The study investigated age-related changes in the thickness of the deep and superficial abdominal muscles of 103 healthy women who could walk independently The participants were classified into five age groups: young (n=26; 20-24 years), young adult (n=26; 25-44 years), middle-aged (n=16; 45-64 years), young-old (n=16; 65-74 years), and old-old (n=19; 75-85 years). The muscle thicknesses of the right rectus abdominis, external oblique, internal oblique, and transversus abdominis were measured using ultrasound imaging. The rectus abdominis was significantly thicker in the young group compared with the young adult, middle-aged, young-old, and old-old groups (p<0.05). The external oblique and internal oblique muscles were significantly thicker in the young group compared with the middle-aged, young-old, and old-old groups (p<0.05). However, there were no significant differences in the thickness of the transversus abdominis between groups. The results suggest that age-related muscle atrophy occurs from an early age in superficial abdominal muscles, such as rectus abdominis, and that age-related atrophy is less in deep abdominal muscles such as the transversus abdominis.     

Successful Treatment of γ-Heavy-Chain Disease with Rituximab and Fludarabine

An 84-year-old Japanese man was admitted because of pancytopenia. The bone marrow was hypoplastic with a predominance of abnormal small lymphocytes and grape cells, which were positive for CD19 and CD20, and partially for the surface ?-light chain. Systemic CT scanning showed neither lymph node swelling nor hepatosplenomegaly. Serum immunoelectrophoresis and rocket immunoselection assays showed the presence of monoclonal IgG protein without a corresponding light chain and faint IgM? monoclonal protein. Histologic analysis of the clot preparation of the bone marrow aspirate facilitated a diagnosis of lymphoplasmacytic lymphoma (LPL). PCR analysis of the marrow cells demonstrated a clonal rearrangement of the immunoglobulin heavy-chain gene. From these results, we made a final diagnosis of γ-heavy-chain disease (γ-HCD) with underlying LPL localized in the bone marrow. We performed only a single course of immunochemotherapy (rituximab and fludarabine) in view of severely impaired hematopoiesis, which resulted in marked reduction of lymphoma cells and improvement of hematopoiesis. This report suggests the efficacy of rituximab plus fludarabine therapy for LPL-associated γ-HCD.     

Continuous proton pump inhibitor treatment decreases upper gastrointestinal bleeding and related death in rural area in Japan

Background and Aims: Proton pump inhibitors (PPI) have been rarely used for prevention of upper gastrointestinal bleeding (UGIB) induced by non‐steroidal anti‐inflammatory drugs (NSAIDs) and/or aspirin in Japan. The increased incidence of UGIB in the aged society is becoming a serious problem. The aim of this study was to retrospectively evaluate whether PPI can prevent UGIB. Methods: We examined records of 2367 patients (aged 67.9 ± 15.1 years, male 1271) attending the only hospital serving the rural area, with little population movement. We investigated the correlation between the frequency of usage of medicine (PPI, histamine 2 receptor antagonists [H2RA], NSAIDs, aspirin) and incidence of UGIB over 12 years. UGIB was defined as cases with hematemesis and/or melena and definite bleeding at upper gastrointestinal endoscopy. The annual incidence of UGIB of inhabitants (16 065 ± 375.3 persons/year) was evaluated. The frequency of usage of medicine was compared with the total number of patients prescribed any medication (1080 ± 33.2 persons/year). Results: The frequency of PPI usage has increased significantly 4.6%→30.8% (P < 0.05). NSAIDs and aspirin usage increased significantly in the latter half of the survey period (P < 0.05). The annual incidence of UGIB significantly decreased 160.8 →23.6/100 000 inhabitants per annum (P ≤ 0.05) due to widespread use of PPI. No patients died due to UGIB after 2006. The incidence of UGIB and the prevalence of PPI usage were found to have a negative correlation (r = ?0.804, P = 0.0016). Conclusions: By widespread use of PPI, UGIB and related death has declined significantly. This survey showed that continuous PPI treatment decreases UGIB and related death in community medicine.     

Effects of bile-acid-binding resin (colestimide) on blood glucose and visceral fat in Japanese patients with type 2 diabetes mellitus and hypercholesterolemia: an open-label, randomized, case-control, crossover study

ObjectiveThe objective was to examine the effects of colestimide on blood glucose, visceral fat, adipocytokines, and bile acid conjugate fractions in Japanese patients.MethodsThis study was an open-label, randomized, case–control, crossover study of colestimide 3 g/day in 40 Japanese patients with type 2 diabetes mellitus (T2D) and hypercholesterolemia. Patients were assigned to the colestimide group in which pravastatin and colestimide were administered orally and to the statin group in which pravastatin alone was administered orally. The principal outcome measures were serum lipid levels, fasting plasma glucose level in the early morning, hemoglobin A1c (HbA_1c), visceral fat area (VFA), and serum 1,5-anhydroglucitol (1,5-AG) level.ResultsSerum low-density lipoprotein cholesterol levels significantly decreased from 113±38 mg/dl at baseline to 90±20 mg/dl (P=.009) at week 12 of colestimide administration. HbA_1c significantly decreased from 7.4%±0.9% at baseline to 6.9%±0.9% (P=.001) at week 12 of colestimide administration. Serum 1,5-AG levels increased from 9.4±10.1 μg/ml to 12.4±9.5 μg/ml (P=.05) at week 12 of colestimide administration. The statin group showed no significant changes in lipids and 1,5-AG. However, ΔVFA was inversely correlated with Δcholic acid, and multivariate analysis revealed that ΔVFA was a significant explanatory variable.ConclusionsColestimide holds promise not only for the treatment of hypercholesterolemia but also for the possible improvement of T2D and visceral fat obesity.     

Complex obstacle negotiation exercise can prevent falls in community‐dwelling elderly Japanese aged 75 years and older

Objectives: The aim of the present study was to evaluate whether a complex course obstacle negotiation exercise (CC), a 24‐week exercise program, can reduce falls and fractures in older adults, as compared with a simple course obstacle negotiation exercise (SC). Methods: This trial was carried out on older adults, aged 75 years and above in Japan. In total, 157 participants were randomized into the CC group (n = 78) and the SC group (n = 79). Participants were enrolled in the exercise class using the CC program or the SC program for 24 weeks. The outcome measure was the number of falls and fracture rates in CC and SC groups for 12 months after the completion of the 24‐week exercise class. Results: Two participants (2.8%) in the CC group and 19 (26.0%) in the SC group experienced falls during 12 months. During the 12‐month follow‐up period after the intervention, the incidence rate ratio (IRR) of falls in the SC group against the CC group was 9.37 (95% CI = 2.26–38.77). One participant (1.4%) in the CC group and eight (10.9%) in the SC group had experienced fractures during 12 months after the exercise class. The IRR of fractures in the SC group compared with the CC group was 7.89 (95% CI = 1.01–61.49). Conclusions: The results of the present trial show that the participants who received individualized obstacle avoidance training under complex tasks combined with a traditional intervention had a lower incidence rate of falls and fractures during the 12 months after the intervention. Geriatr Gerontol Int 2012; 12: 461–467.     

Significant improvement in temporary dental rehabilitation by notable miniplate application in the hard palate for a patient with a large anterior maxillary defect: a case report/technique article

The present report describes the application of a miniplate in the hard palate of a 36-year-old patient with a large anterior maxillary defect. The combination of orthodontic elastics with a titanium miniplate improved the stability of the prefabricated prosthesis. This structure retained the ointment gauze covering the wounds and maintained the facial contour. In addition, contracture deformity was prevented by insertion of the prefabricated prosthesis intraoperatively or immediately postoperatively. Furthermore, a soft diet could be ingested immediately postoperatively. The miniplate also supported the anterior part and the definitive prosthesis. This prosthesis restored adequate masticatory, deglutitive, and speech functions and maintained the facial contour with minimum overloading of the remaining teeth.     

Inhibitory effects of IL-12 on experimental tooth movement and root resorption in mice

ObjectiveInterleukin (IL)-12 is an important cytokine for innate and adaptive immunity. We previously reported that IL-12 inhibits tumour necrosis factor (TNF)-α-mediated osteoclast formation by inducing apoptosis. We also reported that TNF-α plays an important role in mechanical loading-induced osteoclast formation and bone resorption during orthodontic tooth movement. In this study, we investigated the effects of IL-12 on mechanical tooth movement in mice.DesignA Ni–Ti closed coil spring was inserted between the upper incisors and the upper left first molar in mice. IL-12 was injected locally adjacent to the first molar every other day during the experimental period, at doses varying from 0 to 1.5 μg/day. After 12 days, the animals were killed and their jaws were processed for histological evaluation using tartrate-resistant acid phosphatase (TRAP) and TdT-mediated dUTP-biotin nick end-labelling (TUNEL) staining, and measurements of the root resorption area.ResultsIn the IL-12-treated mice, tooth movement and root resorption appeared to be reduced. In TUNEL-stained sections, many apoptotic cells were recognized on the pressure side in the IL-12-treated mice.ConclusionsOur findings suggest that IL-12 inhibits not only mechanical tooth movement, but also root resorption during orthodontic tooth movement. These findings may arise through apoptosis induced by IL-12.