The effect of antireflux treatment on patients with gastroesophageal reflux disease undergoing a mental arithmetic stressor

Background Acute stress exacerbates heartburn in gastroesophageal reflux disease (GERD) patients by enhancing the perceptual responses to intraesophageal acid. The aim of the study was to determine if antireflux treatment can still alter stimulus response functions to acid in patients undergoing acute stress as compared with placebo. Methods Symptomatic GERD patients with erosive esophagitis (EE) or an abnormal pH test were included. Patients underwent stimulus response functions to intraesophageal acid perfusion using the mental arithmetic stressor test. Thereafter, patients were randomized (2 : 1 ratio) to either esomeprazole 40 mg once daily or placebo for 8 weeks. On the last day of treatment, subjects underwent stimulus response functions to intraesophageal acid perfusion using a similar stressor as baseline. Key Results A total of 31 patients were randomized into the treatment arm (mean age 48.6 ± 2.8, M/F 21/10) and 16 into the placebo arm (mean age 52.3 ± 4.3, M/F 12/4). In the esomeprazole group, there was a significant increase in lag time to symptom perception (P = 0.02) and decreased in intensity rating (P = 0.01) as well as acid perfusion sensitivity score (P = 0.01). There was no significant difference in any of the stimulus response functions to acid in the placebo group between baseline and treatment. Interpersonal sensitivity was the only independent clinical predictor factor for response to antireflux treatment. Conclusions & Inferences Long‐term antireflux treatment with a proton pump inhibitor is effective in reducing esophageal perception responses to acid during acute stress.     

抗焦虑抑郁药物对难治性胃食管反流病辅助治疗作用的临床研究

目的 探讨抗焦虑抑郁药物联合质子泵抑制剂对难治性胃食管反流病（RGERD）的治疗作用.方法 将92例RGERD患者分为治疗组和对照组,每组包含26例伴焦虑抑郁者和20例不伴焦虑抑郁者.治疗组给予氟哌噻吨美利曲辛和雷贝拉唑钠肠溶胶囊,对照组给予雷贝拉唑钠肠溶胶囊,疗程均为8周.疗程结束后利用GerdQ量表评价疗效并观察不良反应.治疗组与对照组间以及各组伴有焦虑抑郁患者与不伴有焦虑抑郁患者间进行方差分析.结果 治疗组有效率高于对照组,P＜0.05.治疗组中伴焦虑抑郁者疗效优于不伴焦虑抑郁者,P＜0.05.对照组中伴焦虑抑郁者疗效与不伴焦虑抑郁者疗效无统计学差异,P〉0.05.治疗组中伴焦虑抑郁者疗效优于对照组中伴焦虑抑郁者,P＜0.05.治疗组中不伴焦虑抑郁者疗效与对照组中不伴焦虑抑郁者疗效无统计学差异,P〉0.05.各组均未发生显著不良反应.结论 抗焦虑抑郁药物联合质子泵抑制剂治疗RGERD疗效优于单用质子泵抑制剂.     

Cardiac sympathetic denervation preceding motor signs in Parkinson disease

There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[¹⁸F]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD.     

神经末梢受体在胃食管反流病中的作用

目的探讨辣椒素受体(TRPV1,也称瞬时感受器电位香草酸受体1)在胃食管反流疾病(GERD)患者组织中的表达及其与患者症状的关系。方法利用电子胃镜采集58例GERD患者[反流性食管炎(RE)患者26例,非糜烂性反流病(NRED)患者32例]及胃镜检查正常对象(对照组)的食管黏膜组织(胃食管连接处上方3cm),采用HE染色评估组织炎症反应程度、免疫组化染色S-P法判定组织TRPV1表达情况、反流性疾病诊断问卷(RDQ)对患者的症状评分并进行组间比较和相关性分析。结果 GERD患者的RDQ症状积分、GS炎症积分与对照组比较差异有统计学意义(P0.05);RE患者、NRED患者的RDQ症状积分分别为16.77±5.39、17.52±5.03,均显著高于对照组(P0.05),RE患者NRED患者对照组的GS炎症积分(P0.05)。GERD患者的TRPV1表达OD值显著高于对照组(P0.05),RE组OD值(0.023 1±0.002 6)显著高于NRED组和对照组(P0.05),NRED组显著高于对照组(P0.05)。GERD患者与RDQ症状积分呈显著的正相关(r=0.517),与GS炎症积分呈显著的正相关(r=0.554);RE患者与RDQ症状积分呈显著的正相关(r=0.632),与GS炎症积分呈显著的正相关(r=0.532);NRED患者与RDQ症状积分呈显著的正相关(r=0.671),与GS炎症积分呈显著的正相关(r=0.512)。结论 GERD患者的TRPV1表达显著高于正常人群,且与患者的临床症状、炎症反应的严重程度有一定的相关关系。     

Association of gastroesophageal reflux disease with weight gain and apnea, and their disturbance on sleep.

Obesity is a common predisposition to gastroesophageal reflux disease (GERD) and obstructive sleep apnea syndrome (OSAS). By statistical analysis of the respondents to a questionnaire that was distributed to members of the Kansai Rugby Association, we examined whether weight gain increased the incidence of these diseases and whether GERD alone disturbs sleep. Prevalence distribution of GERD by age differed from another survey, which suggests that predispositions other than age may contribute to GERD. Weight gain tended to increase the incidence of GERD. In our epidemiological study, both GERD (particularly nocturnal reflux) and OSAS significantly contributed to sleep disturbance. Although GERD alone seemed to be one of several independent factors of sleep disturbance, it was not a weak factor.     

Short-term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease

Background Electrical stimulation (ES) of the lower esophageal sphincter (LES) increases resting LES pressure (LESP) in animal models. Our aims were to evaluate the safety of such stimulation in humans, and test the hypothesis that ES increases resting LESP in patients with gastroesophageal reflux disease (GERD). Methods A total of 10 subjects (nine female patients, mean age 52.6 years), with symptoms of GERD responsive to PPIs, low resting LES pressure, and abnormal 24‐h intraesophageal pH test were enrolled. Those with hiatal hernia >2 cm and/or esophagitis >Los Angeles Grade B were excluded. Bipolar stitch electrodes were placed longitudinally in the LES during an elective laparoscopic cholecystectomy, secured by a clip and exteriorized through the abdominal wall. Following recovery, an external pulse generator delivered two types of stimulation for periods of 30 min: (i) low energy stimulation; pulse width of 200 μs, frequency of 20 Hz and current of 5–15 mA (current was increased up to 15 mA if LESP was less than 15 mmHg), and (ii) high energy stimulation; pulse width of 375 ms, frequency of 6 cpm, and current 5 mA. Resting LESP, amplitude of esophageal contractions and residual LESP in response to swallows were assessed before and after stimulation. Symptoms of chest pain, abdominal pain, and dysphagia were recorded before, during, and after stimulation and 7‐days after stimulation. Continuous cardiac monitoring was performed during and after stimulation. Key Results All patients were successfully implanted nine subjects received high frequency, low energy, and four subjects received low frequency, high energy stimulation. Both types of stimulation significantly increased resting LESP: from 8.6 mmHg (95% CI 4.1–13.1) to 16.6 mmHg (95% CI 10.8–19.2), P < 0.001 with low energy stimulation and from 9.2 mmHg (95% CI 2.0–16.3) to 16.5 mmHg (95% CI 2.7–30.1), P = 0.03 with high energy stimulation. Neither type of stimulation affected the amplitude of esophageal peristalsis or residual LESP. No subject complained of dysphagia. One subject had retrosternal discomfort with stimulation at15 mA that was not experienced with stimulation at 13 mA. There were no adverse events or any cardiac rhythm abnormalities with either type of stimulation. Conclusions & Inferences Short‐term stimulation of the LES in patients with GERD significantly increases resting LESP without affecting esophageal peristalsis or LES relaxation. Electrical stimulation of the LES may offer a novel therapy for patients with GERD.     

Suppressed sympathetic skin response in Parkinson disease

The sympathetic skin response (SSR) was used to evaluate sympathetic sudomotor activity in Parkinson disease (PD) and the effects of antiparkinsonian medication on the disease. We recorded SSRs to electric and auditory stimulation in 58 untreated patients with PD and in 20 healthy controls. In addition to amplitude and latency measurements, we examined the number of SSRs evoked by a single stimulus and the response adaptation after repetitive stimuli. The patients with PD subsequently were randomized for administration of levodopa/carbidopa (n=19), bromocriptine (n=20), or selegiline (n=19) as their initial treatment. The measurement were repeated after 6 months of medication and after a washout period. SSR amplitudes were significantly lower in patients with PD than in the control subjects at baseline. The amplitude reduction was more pronounced in patients with high Unified Parkinson's Disease Rating Scale scores, in those with high tremor scores, and in those with PD symptoms that had lasted more than 1 year. The levodopa/carbidopa and bromocriptine treatments did not influence SSRs, although selegiline slightly decreased the amplitude. The synchronous responses after a single stimulus were often repetitive in the patients with PD than in the controls, although the response adaptation tendencies were similar. In conclusion, the degenerative process in PD involves the sudomotor system as reflected by the progressive suppression of SSR amplitudes with a correlation to PD symptom duration and clinical disability, whereas PD medications seems to have only minor effects. The changes in amplitude and the repetitiveness of SSRs with normal adaptation may be caused by deficits at several levels of the SSR reflex arch.     

The effect of baclofen on nocturnal gastroesophageal reflux and measures of sleep quality: a randomized, cross-over trial

Background Baclofen, a GABA_b agonist, has been shown to reduce episodes of gastroesophageal reflux (GER). To determine if baclofen would significantly reduce reflux during sleep, and also improve objective and subjective measures of sleep. Methods Twenty‐one individuals with complaints of nighttime heartburn at least twice a week and a Carlsson GERD score of at least 5 were studied. Patients underwent polysomnography (PSG) and simultaneous esophageal pH monitoring on two occasions separated by approximately 1 week in a cross‐over design. The night of each polysomnographic study, patients consumed a refluxogenic meal. Baclofen (40 mg) or placebo was given in random order 90 min prior to the start of the PSG. Key Results Baclofen significantly reduced the number of reflux events compared with placebo. Upright and recumbent acid contact times were both reduced by baclofen vs placebo, but the differences were not significant. Regarding sleep outcomes, several variables were significantly improved by baclofen. Total sleep time and sleep efficiency increased, and wake after sleep onset decreased in the baclofen condition compared with placebo. Proportion of Stage 1 sleep was also significantly decreased on baclofen. Conclusions & Inferences In addition to reducing the number of reflux events during sleep, baclofen significantly improved several measures of sleep in patients with documented GER and sleep disturbances. Baclofen could therefore be considered as a useful adjunct therapy to proton pump inhibitors (PPIs) in patients with nighttime heartburn and sleep disturbance who continue to have heartburn and/or sleep complaints despite PPI therapy.