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.     

Blue laser imaging identifies endoscopic findings corresponding to metachronous esophageal squamous cell carcinoma

Esophagus - This study aimed to evaluate endoscopic findings using non-magnifying blue laser imaging (BLI) to determine the risk factors for metachronous esophageal squamous cell carcinoma (ESCC)....     

The role of Na+/H+ exchange in norepinephrine-induced protein synthesis in neonatal cultured rat cardiomyocytes

It is reported that Na+ influx contributes to stretch-induced cardiac hypertrophy. Na+ influx may also be involved in cardiac hypertrophy induced by catecholamine. In the present study, to test whether Na+/H+ exchange plays an important role in norepinephrine-induced cardiac hypertrophy, the effect of Na+/H+ exchange inhibitor, amiloride on protein synthesis was studied in cultured neonatal rat cardiomyocytes in serum free medium. [3H]Phenylalanine uptake was determined 24 and 48 hours after administration of norepinephrine with and without amiloride. In the control, norepinephrine increased [3H]phenylalanine uptake in a dose dependent manner (10(-5)-10(-7) M). Prazosin (10(-7) M) and amiloride (10(-5)-10(-4) M) significantly attenuated the norepinephrine mediated protein synthesis. These results indicate that alpha 1-adrenergic stimulation enhances the protein synthesis through activation of Na+/H+ exchange. Therefore, Na+ influx and/or PH increase may play a key role in cardiac hypertrophy.     

Changes in arrhythmogenic properties and five‐year prognosis after carbon‐ion radiotherapy in patients with mediastinum cancer

Introduction

Carbon‐ion irradiation of rabbit hearts has improved left ventricular conduction abnormalities through upregulation of gap junctions. However, to date, there has been no investigation on the effect of carbon‐ion irradiation on electrophysiological properties in human. We investigated this effect in patients with mediastinum extra‐cardiac cancer treated with carbon‐ion radiotherapy that included irradiating the heart.

Methods and Results

In April–December 2009, eight patients were prospectively enrolled (including two male, aged 72.5 ± 13.0 years). They were treated with 44–72 Gray equivalent (GyE), with their hearts exposed to 1.3–19.1 GyE. High‐resolution ambulatory electrocardiography was performed before and after radiotherapy to investigate arrhythmic events, late potentials (LPs), and heart rate variability. Five patients had pre‐existing premature ventricular contraction (PVC)/atrial contraction (PAC) or paroxysmal atrial fibrillation (PAF)/AF; after irradiation, this improved in four patients with PVC/PAF/AF and did not deteriorate in one patient with PAC. Ventricular LP findings did not deteriorate and improved in one patient. In eight cases with available atrial LP findings, there was no deterioration, and two patients showed improvements. The low frequency/high frequency ratio of heart rate variability improved or did not deteriorate in the six patients who received radiation exposure to the bilateral stellate ganglions. During the five‐year follow‐up for the prognosis, six of the eight patients died because of cancer; there was no history of hospitalization for cardiac events.

Conclusion

Although this preliminary study has several limitations, carbon‐ion beam irradiation to the heart is not immediately cardiotoxic and demonstrates consistent signals of arrhythmia reduction.

     

Effect of cigarette smoking on the gastric mucosal blood volume index and hemoglobin oxygenation in man

The acute effect of cigarette smoking on the gastric mucosal blood volume index and the oxygen saturation of hemoglobin (SO₂) in the gastric mucosa was investigated in 12 young male volunteers using reflectance spectrophotometry during endoscopy. Six of these volunteers were habitual smokers who had smoked more than 20 cigarettes a day for more than five years. The others were non-habitual smokers who smoked less than 20 cigarettes a year. The indices of mucosal blood volume and the mucosal blood SO₂ level were calculated from the spectra obtained at the lesser curvature of the lower corpus of the stomach before and after cigarette smoking. The indices of mucosal blood volume and mucosal blood SO₂ decreased significantly after one to three puffs of cigarette smoking in all subjects as compared to the value before smoking, and the degree of decrease in these parameters was significantly greater in the non-habitual smokers than in the habitual smokers. These results suggest that only one to three puffs of cigarette smoking causes a decrease in the mucosal blood volume and the mucosal blood SO₂ which might be related to weakening of mucosal defensive factors. This work was supported by a grant from the Japan Tobacco Corporation.     

The improvement of the enforcement rate of the standard regimen (A) of tuberculosis chemotherapy by the introduction of common database system for tuberculosis

OBJECTIVE: The purpose of this study was to improve the enforcement rate of the standard regimen (A) of tuberculosis chemotherapy. SUBJECTIVE AND METHODS: We introduced the common database system for tuberculosis in three national hospitals in Hokkaido. From January 2002 to December 2003, we collected the anonymous informations of the patients with tuberculosis at the start of treatment, at the discharge and at the end of treatment. Then, we reported the enforcement rate of the standard regimen (A) as a clinical indicator periodically to three hospitals. RESULTS: Four hundred and twenty-nine patients were registered. In patients below 80 years old, the enforcement rate of the standard regimen (A) was 48.5% in 2002. The enforcement rate rose significantly to 62.7% (p = 0.0126) in 2003. In elder smear-positive patients (> or =75) and in elder smear-negative patients (> or =70), the enforcement rate was low (29.1% and 25.0%, respectively). Furthermore in young smear-negative patients (< or =29), the enforcement rate was low (28.0%). As the extent of their disease was minimal, they were treated with other regimens. In patients treated with the standard regimen (A), there were no significant differences in the frequency of adverse effects between elder patients ( 70) and other patients (< or =69). There were also no significant differences in the frequency of changing the regimen between them. Median admission period of 2002 was 114 days. In 2003, it was shortened significantly to 110 days (p = 0.0487). CONCLUSION: By the introduction of the common database system for tuberculosis, the enforcement rate of the standard regimen (A) was improved. Low enforcement rate in young smear-negative patients in an important problem to be improved in the future. The clinical indicator based on the common database system between hospitals, is useful to clarify the problems, and then to improve the quality of medical performance.     

Eradication of Helicobacter pylori increases the incidence of hyperlipidaemia and obesity in peptic ulcer patients

BACKGROUND: Eradication of Helicobacter pylori improves clinical symptoms and quality of life in patients with peptic ulcer. AIM: To investigate the effect of eradication of H. pylori on body mass index and incidence of hyperlipidaemia in patients with peptic ulcer. PATIENTS AND METHODS: The study population comprised 50 patients (42 men, 8 women; mean age, 51 years; 28 gastric ulcer, 22 duodenal ulcer) who underwent physical and blood examination before and 1 year after undergoing eradication therapy and 100 sex- and age-matched control subjects. Body mass index, total cholesterol and triglyceride were measured before and 1 year after therapy. RESULTS: The eradication therapy group showed a significant increase in body mass index (22.7+/-2.5 kg/m2 before eradication versus 23.6+/-2.6 kg/m2 after eradication, p < 0.01), serum total cholesterol (204.1+/-33.2 mg/dL versus 221.2+/-38.8 mg/dL, p < 0.01), and triglyceride. Additionally, the eradication therapy group showed a significant increase in the incidence of hypercholesterolemia (30% versus 58%, p<0.01), hypertriglyceridaemia (28% versus 44%, p < 0.01) and obesity (12% versus 22%, p <0.05) 12 months after therapy. CONCLUSION: Our findings show that eradication of H. pylori significantly increases the incidence of hyperlipidaemia and obesity in patients with peptic ulcer.