非糜烂性反流病与功能性烧心

罗马Ⅲ标准提出了非糜烂性反流病(NERD)和功能性烧心(FH)的诊断标准,实际上,临床上有时很难区分NERD和FH。NERD和FH是两种发病机制及临床特点不同的异质性疾病,本综述结合目前研究进展,从食管内脏敏感性、食管动力、精神心理因素、与功能性疾病关系、症状特点及治疗效果方面阐述两者特点,并探讨其相互关系。     

Detailed esophageal function and morphological analysis shows high prevalence of gastroesophageal reflux disease and Barrett's esophagus in patients with cervical inlet patch

Although the pathogenesis of cervical inlet patch (CIP) is not fully understood, most authors consider it as a congenital abnormality, whereas others surmise it to be related to gastroesophageal reflux disease (GERD). We aimed to evaluate esophageal function and the prevalence of GERD and Barrett's esophagus in patients with CIP. GERD is defined by the presence of erosive esophagitis or an abnormal pH monitoring. Seventy-one consecutive patients with endoscopic and histological evidence of CIP were prospectively evaluated. Esophageal symptom analysis, 24-hour simultaneous biliary reflux and double-channel pH-monitoring, and esophageal manometry were carried out in 65/71 (92%) patients and in 25 matched controls. Six patients were not suitable for testing and were, therefore, excluded. The histological evaluation of the heterotopic islands showed cardia and/or oxyntic mucosa in 64/65 (98%) patients and specialized intestinal metaplasia (SIM) in one patient (2%). The cardia and/or oxyntic mucosa was accompanied by focally appearing pancreatic acinar metaplasia and pancreatic ductal metaplasia in 7/64 (11%) and in 1/64 (2%), superficial mucous glands in 6/64 (9%), and SIM in 2/64 (3%) cases. In total, SIM was present in three patients (5%), and one of them had low-grade dysplasia. At the gastroesophageal junction, 28 (43%) patients had columnar metaplasia, including nine (14%) patients with SIM. Erosive esophagitis was present in 37 (57%) cases. Thirty-two patients (49%) had abnormal acid reflux in the distal and 25 (38%) in the proximal esophagus. Abnormal biliary reflux was present in 25 (38%) cases. On the basis of endoscopic and pH studies, GERD was established in 44/65 (68%) patients. Typical reflux symptoms were common (33/65, 51%). The combined 24-hour biliary and double-channel pH-monitoring detected significantly more significant acidic reflux at both measurement points and significantly longer bile exposure time in the distal esophagus in patients with CIP. Acid secretion in the CIP was detected in three (5%) cases. Esophageal manometry revealed decreased LES pressure and prolonged relaxation with decreased peristaltic wave amplitude, and an increased number of simultaneous contractions in the esophageal body. The detailed evaluation of the esophageal morphology and function in subjects with CIP showed a high prevalence of GERD and Barrett's esophagus. Further studies are needed to evaluate whether combined acidic and biliary reflux is able to promote similar histomorphological changes in the CIP, as it is shown distally in patients with Barrett's esophagus.     

Non-erosive reflux disease, functional heartburn and gastroesophageal reflux disease; insights into pathophysiology and clinical presentation

Non-erosive reflux disease (NERD) has emerged as a real entity in the spectrum of gastroesophageal reflux disease (GERD) and may, indeed, represent the most common manifestation of reflux disease. Recent information indicates NERD can be further subclassified based on the results of pH studies and suggests that functional heartburn needs to be differentiated as that subgroup of patients in which there appears to be no relationship between symptoms, however 'typical' of GERD, and acid exposure. Other aspects of NERD need to be appreciated, including overlap with functional dyspepsia and the potential variations in response to such therapeutic interventions as acid-suppressive therapy and fundoplication. It seems quite possible that our failure to separate functional heartburn from NERD, in general, has contributed, in large measure, to diagnostic difficulties and therapeutic disappointment in GERD. An appreciation of the range of entities, of different etiology and pathology, within NERD will foster the development of effective approaches to the assessment and therapy of this challenging disorder.     

Gi protein activation in intact cells involves subunit rearrangement rather than dissociation

G protein-coupled receptors transduce diverse extracellular signals, such as neurotransmitters, hormones, chemokines, and sensory stimuli, into intracellular responses through activation of heterotrimeric G proteins. G proteins play critical roles in determining specificity and kinetics of subsequent biological responses by modulation of effector proteins. We have developed a fluorescence resonance energy transfer (FRET)-based assay to directly measure mammalian G protein activation in intact cells and found that Gi proteins activate within 1-2 s, which is considerably slower than activation kinetics of the receptors themselves. More importantly, FRET measurements demonstrated that Galphai- and Gbetagamma-subunits do not dissociate during activation, as has been previously postulated. Based on FRET measurements between Galphai-yellow fluorescent protein and Gbetagamma-subunits that were fused to cyan fluorescent protein at various positions, we conclude that, instead, G protein subunits undergo a molecular rearrangement during activation. The detection of a persistent heterotrimeric composition during G protein activation will impact the understanding of how G proteins achieve subtype-selective coupling to effectors. This finding will be of particular interest for unraveling Gbetagamma-induced signaling pathways.     

Pathological bolus exposure may define gastro-esophageal reflux better than pathological Acid exposure in patients with globus

Background/Aims: Conventionally, pathological acid exposure (PAE), defined by acid reflux only, is used to identify gastro-esophageal reflux disease (GERD). However, weak acid reflux or non-acid reflux also induces reflux symptoms. Defining abnormal reflux based on all reflux episodes may better identify GERD and would be more useful among patients with atypical GERD symptoms, such as globus. Methodology: Impedance-pHmetry results of 31 globus patients, off acid suppressants, were analysed. Results: A median of 24 episodes of reflux were observed. Of the reflux episodes, 54% were non-acid reflux and 50% reached the proximal extent. PAE was observed in 6 patients (19%). For 5 patients (16%) without PAE, there was evidence of increased bolus exposure compared to normal controls (an intraesophageal bolus exposure for more than 1.4% of the recording time, defined as pathological bolus exposure, PBE). When GERD was defined by PAE or esophagitis, the prevalence of GERD was 29%. When GERD was defined by PBE, PAE or esophagitis, the prevalence was 42%. PBE identified 13% of the patients who otherwise would have been missed. Conclusions: A significant proportion of patients without PAE had evidence of PBE. PBE may be a more useful definition for identifying patients with abnormal increase in reflux in patients with globus. Further studies are warranted.     

胃食管反流病与颈椎病相关性研究

目的探讨颈椎病患者是否为胃食管反流病(gastroesophageal reflux disease,GERD)的高发人群。方法 321例经临床及磁共振诊断为颈椎病的患者作为颈椎病组,同期选取249名健康体检者作为对照组,进行RDQ评分问卷调查,比较颈椎病组及对照组的RDQ评分及GERD发生率差异是否有统计学意义,颈痛程度与RDQ评分是否相关,并对可能危险因素及颈椎病分型情况进行统计学分析。结果颈椎病组RDQ评分明显高于对照组(P0.05);以RDQ评分≥12分作为GERD评判标准,颈椎病组GERD 43例(13.4%),对照组GERD 17例(6.8%),颈椎病组GERD发生率明显高于对照组(P0.05);不同颈痛程度组间RDQ评分差异有统计学意义(P0.05);各型颈椎病中,交感神经型发生GERD的风险明显高于其他各型(P0.05);颈椎病合并GERD的危险因素主要为女性、非甾体抗炎药和精神心理因素。结论颈椎病患者发生GERD的风险较高,且以交感神经型最为显著。女性、药物和精神心理因素是颈椎病合并GERD的主要危险因素。     

Females without reflux symptoms or gastroesophageal reflux disease have less distal esophageal acid exposure than males without reflux symptoms or gastroesophageal reflux disease

Ambulatory 24‐hour esophageal pH monitoring is the gold standard examination to assess esophageal acid exposure. Gender‐related variation is a well‐recognized physiologic phenomenon in health and disease. To date, limited gender‐specific 24‐hour esophageal pH monitoring data are available. The aim of this study was to obtain values of esophageal pH monitoring in males and females without reflux symptoms or gastroesophageal reflux disease (GERD) to determine if gender variation exists in esophageal acid exposure among individuals without these factors. Twenty‐four‐hour dual esophageal pH monitoring was performed in male and female volunteers without reflux symptoms or GERD. Values for total number of reflux episodes, episodes longer than 5 minutes, total reflux time in minutes, % time with pH below 4, and longest reflux episode in the proximal/distal esophagus were obtained and recorded for both groups. The distal channel was placed 5 cm and proximal channel 15 cm above the manometrically determined lower esophageal sphincter. Means were compared using an independent sample t‐test. Sixty‐seven males and 69 females were enrolled. All subjects completed esophageal 24‐hour pH monitoring without difficulty. There was no age or body mass difference between groups. Females had significantly fewer reflux episodes at both esophageal measuring sites and, significantly less total reflux time and % time with pH below 4 in the distal esophagus than males. All other parameters were similar. Significant gender‐related differences exist in esophageal acid exposure, especially in the distal esophagus in individuals without reflux symptoms or GERD. These differences underscore the need for gender‐specific reference values for 24‐hour pH monitoring, allowing for an accurate evaluation of esophageal acid exposure in symptomatic patients.     

Heart disease risk determines menopausal age rather than the reverse.

OBJECTIVES: The purpose of this study was to investigate whether a harmful cardiovascular risk profile accelerates menopause. BACKGROUND: Women with an early menopause are at an increased risk of cardiovascular disease. Although increased cardiovascular risk has been proposed as consequence of menopause, the alternative hypothesis, that increased premenopausal cardiovascular risk promotes early menopause, needs to be examined. METHODS: We used data from the Framingham Heart Study cohort. This study started in 1948 and has followed up participants biennially since then. Women who were premenopausal at study entry and who reached natural menopause after at least two examination rounds were included in the study (n = 695). Premenopausal age-independent levels of serum total cholesterol, relative weight, blood pressure, and Framingham risk score were determined, as well as premenopausal changes in cholesterol, body weight, and blood pressure. RESULTS: A higher premenopausal serum total cholesterol level was statistically significantly associated with an earlier age at menopause, as were increases in total serum cholesterol, relative weight, and blood pressure in the premenopausal period. A decrease in total serum cholesterol during premenopause was statistically significantly associated with later age at menopause. Decreasing blood pressure was associated with a later menopausal age, but this association was not statistically significant. A decrease in relative weight was associated with a significant earlier age at menopause. Each 1% higher premenopausal Framingham risk score was associated with a decrease in menopausal age of 1.8 years (95% confidence interval -2.72 to -0.92). CONCLUSIONS: The findings support the view that heart disease risk determines age at menopause. This offers a novel explanation for the inconsistent findings on cardiovascular disease rate and its relationship to menopausal age and effects of hormone replacement therapy.     

Intentional examination of esophagus by narrow‐band imaging endoscopy increases detection rate of cervical inlet patch

Foci of heterotopic gastric mucosa have been identified at different sites in the human body and the most common location is the proximal esophagus which is referred to as cervical inlet patch (CIP). The true prevalence of CIP varies and it is usually incidental findings during endoscopy. Because CIP is always asymptomatic, it was believed to be of little clinical relevance. However, emerging studies have described the acid‐secreting characteristics of heterotopic gastric mucosa and associations of CIP with gastroesophageal reflux disease (GERD). In addition, complications such as stricture, fistula, infection, mucosal hyperplasia, and malignant transformation have been reported. In this study, we investigated the prevalence of CIP, its associations with clinical manifestations, and the effect of intentional screening upper esophagus by magnifying endoscopy‐narrow‐band imaging (ME‐NBI) system. Consecutive healthy adults who underwent panendoscopy were separated into two groups. Patients in group I (n = 471) were examined by an endoscopist who intended to find CIPs by ME‐NBI. Patients in group II (n = 428) were examined by two endoscopists who were unaware of the study and performed white‐light imaging endoscopy. Participants provided questionnaires on GERD‐related symptoms. Higher CIP prevalence (11.7% vs. 1.9%, P < 0.0001) and longer duration of esophageal examination (mean ± standard deviation, 17.50 ± 12.40 vs. 15.24 ± 10.78 seconds, P = 0.004) were noted in group I than in group II. Analyzing group I patients revealed the higher prevalences of reflux symptoms (32.7% vs. 18.3%, P = 0.013) and erosive esophagitis (43.6% vs. 25.5%, P = 0.005) in patients with CIP than in those without. CIP was not associated with globus or dysphagia symptoms. More small CIPs (<5 mm) were detected by ME‐NBI than by white‐light imaging (85.3% vs. 41.4%, P = 0.001). In conclusion, CIP prevalence was not low under intentional ME‐NBI examination of the upper esophagus. The clinical relevance of CIP and its association with GERD require further investigation.     

Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease

BACKGROUND/AIMS: As compared to other chronic liver diseases, cholestatic disorders are associated with a better outcome of variceal bleeding and less blood loss at transplantation, suggesting the presence of a hypercoagulable state. We have assessed plasmatic coagulation and platelet function in patients with cholestatic and non-cholestatic liver disease. METHODS: Thirty-seven patients with chronic cholestatic liver disease (primary biliary cirrhosis (PBC)/primary sclerosing cholangitis (PSC)), 53 patients with chronic hepatitis C (HCV) or alcoholic cirrhosis (C2), and 62 healthy controls were studied. RESULTS: Thrombelastography revealed a hypercoagulable state in non-cirrhotic patients with PBC/PSC, but not in those with HCV (ma-value: 6.54[6.25-6.92, 95%CI] vs. 5.39[5.11-5.58], P < 0.05) possibly due to higher fibrinogen levels in PBC/PSC patients (369[329-418]mg/dl vs. 263[250-275]mg/dl, P < 0.05). PFA-100 closure time was prolonged in HCV/C2 patients with advanced cirrhosis, but not in cirrhotic patients with PBC/PSC (Child B; epinephrine stimulation: 192[161-229]s vs. 132[105-158]s, P < 0.05). Flow cytometric studies of platelet receptors and granules revealed a higher surface expression of CD42b (112[105-119]% vs. 100[95-104]%, P < 0.05) and LIBS-1 (261[184-348]% vs. 121[92-145]%, P < 0.05) in patients with PBC/PSC than in those with HCV/C2. CONCLUSIONS: These results indicate that platelet function differs between patients with cholestatic and non-cholestatic liver disease and is stable or even hyperactive in patients with PBC and PSC.