Medical therapy of gastroesophageal reflux disease in secondary and tertiary care settings

Gastroesophageal reflux disease (GERD) is common. Many patients with recurring or troublesome symptoms are referred for endoscopic examination. Patients seen in secondary care usually have failed OTC or primary care anti-reflux therapy. Acid suppression is the mainstay of healing and maintenance therapy. Increasingly proton pump inhibitors (PPIs) are preferred above H2 receptor antagonists (H2RAs), not only for the more severe end of the GERD spectrum but also for patients with mild degrees of esophagitis. Not all patients respond symptomatically to acid suppression, not even with high dose PPI. Prokinetics are mainly useful in the milder degrees of GERD. It is still not clear whether a particular symptom cluster can be recognized for which prokinetics are especially useful. The concept of "step-up versus step-down" approach remains in need for proper validation. Switching from PPIs to cisapride for "step-down" maintenance appears inadequate in practice. All current therapies have shortcomings; H2RAs insufficiently block meal-stimulated acid secretion; long-term strong acid suppression worsens Helicobacter pylori-associated inflammation in the corpus and may accelerate development of atrophy; PPI-potency is substantially weaker in non-H. pylori infected individuals. Optimization of individualized therapy will require more potent and more precisely targeted motility modulating drugs and superior acid/peptic inhibiting pharmaceuticals.     

埃索美拉唑联合莫沙比利干预老年性反流性食管炎临床研究

目的：探讨埃索美拉唑联合莫沙比对老年性反流性食管炎临床疗效。方法：选择符合2003年反流性食管炎诊断及治疗指南诊断标准的160例老年反流性食管炎患者,随机分为治疗组（埃索美拉唑联合莫沙比利）和对照组（奥关拉唑）,观察治疗前后内镜下疗效及症状评分变化。结果：治疗组内镜下病变较对照组显著缓解,总有效率高于对照组,症状评分明显低于对照组,两者间差异有统计学意义（P〈0．05）,且治疗中未发现明显不良反应。结论：埃索美拉唑联合莫沙比利对老年性反流性食管炎有较好的治疗效果,具有很高的临床应用价值。     

Ambulatory pH monitoring of gastro-oesophageal reflux in "morning dipper" asthmatics.

A causal relation between gastro-oesophageal reflux and nocturnal asthma has been postulated. Forty four adult asthmatics underwent ambulatory monitoring of their oesophageal pH over 24 hours to find out if there was such a relation. Of these 21 showed significant "morning dipping" in which the peak expiratory flow falls during the night. Asthmatics with morning dipping had a history of nocturnal wheeze and a higher incidence of reflux symptoms, but measurement of oesophageal pH showed no significant difference in the amount or pattern of reflux when compared with "non-dippers." Overall, 15 asthmatics had gastro-oesophageal reflux, and these participated in a randomised, double blind crossover trial of ranitidine versus placebo. No significant difference was found in the peak expiratory flow rates or subjective evaluation of well being of the patients.     

Earliest Symptoms of Coronary Heart Disease and their Recognition

We have reviewed the histories of 320 patients in whom a diagnosis of coronary heart disease was ultimately established and traced the symptoms back to their first appearance. In 51% the first symptom was effort angina. Difficulties in recognition arose when the symptom was localized to an unusual site, when its occurrence was dependent on a combination of exercise with cold or a recent meal, or when it was induced by excitement rather than by effort. In a quarter of the cases the onset of angina was abrupt, and in these there was usually evidence of acute infarction.In 43% of cases the first symptom was an attack of pain or discomfort in the torso occurring without any discernable precipitating factor. Again, diagnosis was difficult when the pain was in an atypical site and also when it was of brief duration associated with skeletal or abdominal disease which could cause pain at the same site, or if the patient was able to undertake strenuous exertion. In four patients cardiac pain was first experienced during a paroxysm of tachycardia. In 6% of cases the onset was marked by a symptom other than pain—most frequently dyspnoea, tiredness, faintness, or syncope.Clinical examination was of no direct value in diagnosis. Its importance lay in disclosing factors which had to be taken into account in interpreting the electrocardiogram. The electrocardiogram was invaluable, though by no means infallible. In over half of the patients the first tracing showed major abnormalities of coronary type, and nearly a quarter more showed minor S-T/T depression consistent with coronary disease. Ten per cent. showed miscellaneous abnormalities, such as left ventricular hypertrophy or bundle-branch block, and 15% no definite abnormality.There is as yet no completely reliable objective method of diagnosing early coronary heart disease, so that the recognition of symptoms remains of paramount importance.     

Primary amenorrhoea: the ambiguous non-entity.

Hypothalamic-pituitary activity was investigated in 20 women with primary amenorrhoea, in whom gonadal dysgenesis and lower Müllerian duct anomalies had been excluded. There was no specific or uniform pattern of response to luteinising hormone-releasing hormone and no evidence of a common defect at pituitary-hypothalamic level to account for the absence of spontaneous menstruation. Six women had hyperprolactinaemia; of these five had radiological evidence of pituitary enlargement. The conventional distinction between "primary" and "secondary" amenorrhoea should be abandoned, and, in common with current practice for other endocrine glands, primary amenorrhoea should indicate an abnormality of the gonad itself and secondary amenorrhoea an abnormality that results from hypothalamic-pituitary dysfunction.     

A clinical scoring system for detection of patients with pheochromocytomas

We analyzed the medical records of patients admitted to 11 hospitals over a 15-year period, looking for those with metabolically active sporadic pheochromocytomas (Group A) and those in whom the diagnosis was highly suspect but excluded (Group B). Fifty-three patients in Group A and 25 patients in Group B were found. We then devised a scoring system based on the presence or absence of typical symptoms and signs (SSS) and another which also included the results of routine 24-hour urine studies for catecholamines or metabolites (SSLS). The point values given for each symptom and sign were based on those felt to be most characteristic of the disease and points were subtracted if the typical manifestation was absent. Additional points were given if the symptom or sign were paroxysmal. In a high-risk population, the sensitivity of the SSS and the SSLS was 96 percent and the specificity was 64 percent and 88 percent, respectively. The predictive value of a positive SSS was 85 percent and of a positive SSLS was 94 percent. In a large group of patients with essential hypertension (Group C) only 17 of 385 (4.4 percent) had a positive SSS and only one of 385 had a positive SSLS. We feel this scoring system can help detect those hypertensive patients in whom further extensive and potentially invasive evaluation is warranted.     

Antithrombin III Padua: a "new" congenital antithrombin III abnormality with normal or near normal activity, normal antigen, abnormal migration and no thrombotic disease

A "new" antithrombin III abnormality is described in four members of a family. The proposita is a 38 years old female who showed no thrombotic disease and the following laboratory pattern: normal routine clotting tests, normal or near normal AT III activity (chromogenic substrates S-2238 and Chromozym Th) both in plasma and in serum and in the presence or absence of heparin, slightly decreased antifactor Xa activity (chromogenic substrate S-2222), normal progressive antithrombin, normal AT III antigen but abnormal migration in the agarose-heparin bidimensional system. In the latter test, one major abnormal peak, less anodal than the normal counterpart, and a smaller, apparently normal peak, were seen. In agarose without heparin the pattern was similar to normal both in plasma and in serum. Heparin tolerance to heparin in vivo and in vitro was slightly increased but still within normal limits. The two sons and a paternal aunt showed the same pattern. The hereditary pattern seems therefore autosomal dominant. The abnormality described appears different from AT III Budapest. The toponym of antithrombin III Padua is proposed to define this peculiar abnormality.     

Endoscopic studies of dyspepsia in a general practice.

In an urban general practice serving 7800 patients, all patients presenting over five and a half years with dyspepsia lasting more than two weeks were investigated by fibreoptic endoscopy and cholecystography, and many by barium meal. Of the 393 patients with dyspepsia, 346 completed the investigation: 180 had specific disease of the oesophagus, stomach, duodenum, or gall bladder, including six with carcinoma. Al further 67 had mucosal disease, and only 99 patients had no abnormality. After the first year the number of patients presenting annually and the percentage of patients with specific lesions remained constant. The annual incidence for patients with dyspepsia was about 1% and for patients with specific lesions 0.4%, suggesting that each year those who became symptom free (either spontaneously or because of treatment) were balanced by a similar number who developed symptoms. In contrast to the conclusions of other workers that an "open-access" endoscopy service could not be justified because the number of patients with specific lesins fell during their survey, we suggest that such endoscopy services are indeed worth while for providing an accurate diagnosis of dyspepsia.     

Radiology and endoscopy in acute upper gastrointestinal bleeding.

Of 112 patients admitted with acute upper gastrointestinal bleeding, the presumed bleeding site was detected in 61-5% of cases by radiology and in 57% of cases on endoscopy. Thirty-one patients who had barium-meal examination were operated on and the surgical and radiological findings agreed in 26 (84%). Twenty-three patients who had endoscopy were operated on and the surgical and endoscopic findings agreed in 15 (65%). In 10 cases radiology detected a lesion not identified on endoscopy and in nine endoscopy detected a lesion not seen at radiology. We suggest that when there are two potential sources of bleeding radiology as well as endoscopy can detect the actively bleeding lesion. The supplementary nature of radiology and endoscopy is emphasised and we conclude that both methods should be used if there is any doubt at the initial radiological or endoscopic examination about the source of the bleeding.     

Current Management Strategies in Acid-Related Disorders

Acid-related disorders include not only reflux esophagitis and peptic ulcer, but also a subset of patients with endoscopy-negative dyspepsia. The management strategy differs between these diseases and therefore a precise diagnosis is important. The unaided clinical diagnosis is of limited value in patients with pain or discomfort in the upper abdomen, and endoscopy is therefore an important and cost-effective diagnostic tool.Duodenal ulcer is caused by an interplay between gastric acid and Helicobacter pylori. The treatment is aimed at rapid symptom relief and healing and at the same time eradication of H. pylori. At present the best choice is the combination of a proton pump inhibitor and two effective antimicrobial drugs, e.g., clarithromycin and metronidazole. The proton pump inhibitor has dual effect in this combination it provides optimal symptom relief and healing, and it increases the anti-H. pylori-effect of the antimicrobial drugs. The risk of reinfection varies geographically; in Europe it is around 1 percent per year, and cure of the infection provides long-term, maybe life-long, cure of the ulcer disease. Some gastric ulcers are not H. pylori-related and the treatment strategy therefore includes a diagnostic test for this infection. If positive, treatment is similar to that in duodenal ulcer, while H. pylori-negative gastric ulcer patients are treated with antisecretory drugs alone.Reflux esophagitis correlates with the degree of acid exposure to the esophagus, and intensive acid inhibition is the most effective non-surgical therapy. In most cases the disease is chronic and needs continuous long-term therapy to prevent relapse. A staged reduction in dosage of the acid inhibitory drug may be attempted when the esophagitis is healed and the patient has become symptom free, but full dose therapy is often needed.Patients with endoscopy-negative dyspepsia are a heterogenous group and a more precise identification of the cause of the symptoms is a prerequisite for rational treatment. Empiric treatment can be tried in patients without alarm symptoms like bleeding or a palpable abdominal mass, and often an acid inhibitory drug is used. A more precise identification of those patients who have acid-related symptoms is possible using placebo controlled single-subject trials with an effective acid inhibitory drug, but in daily routine these drugs are simply given for a short period of time, and in case symptomatic relief is observed, the symptoms may be regarded as being acid-related and treated accordingly.     

一种新型国产内镜射频消融治疗仪对胃食管反流病的疗效

目的:探讨一种新型国产内镜射频消融治疗仪对胃食管反流病(GERD)的疗效。方法:选取2016年6月-2017年6月来我院就诊的难治性GERD患者50例,随机分为内镜射频治疗组(美顿Medi誖射频治疗仪,n=25)与药物治疗组(n=25)。比较两组患者干预前后的酸反流严重程度、胃食管反流病自测量表(GerdQ)评分、质子泵抑制剂(PPI)的药物使用率、简明健康调查量表(SF-36)评分。结果:(1)内镜射频治疗组患者干预后即刻的胃镜提示射频消融治疗区域的消化道黏膜出现收缩、增厚,干预后6、12个月分别有15例(60.0%)、20例(80.0%)的食管下段黏膜的充血带较前减少。(2)两组干预后3、12个月的GerdQ总分均显著低于干预前(P0.05),内镜射频治疗组干预后3、12个月的GerdQ总分均显著低于同期药物治疗组(P0.05)。(3)全部患者干预前均需要药物来缓解症状,内镜射频治疗组干预3、12个月时的PPI药物使用率均显著低于药物治疗组(P0.05)。(4)内镜射频治疗组干预后SF-36的生理职能、生命活力、精神状态、总体健康等维度评分均显著高于同期药物治疗组(P0.05)。结论:美顿Medi?射频治疗仪对GERD患者是一种安全、有效的治疗选择,能显著改善反流症状,减少PPI药物使用,提高患者的生活质量。     

Eradicating Helicobacter pylori and symptoms of non-ulcer dyspepsia.

OBJECTIVE--To examine the effect of eradication of Helicobacter pylori on symptoms of non-ulcer dyspepsia. DESIGN--Four week prospective study. SETTING--One hospital outpatient and endoscopy department. PATIENTS--90 adults with persistent symptoms typical of non-ulcer dyspepsia but no clinical or endoscopic evidence of other peptic, biliary, pancreatic, or malignant disease; all had histological and microbiological evidence of infection with H pylori. 83 patients completed the treatment regimen. INTERVENTION--Colloidal bismuth subcitrate 120 mg four times a day for four weeks (27 patients); metronidazole 400 mg and amoxycillin 500 mg each three times a day for one week (27); and bismuth subcitrate 120 mg four times a day for four weeks, metronidazole 400 mg three times a day for one week, plus amoxycillin 500 mg three times a day for the first week (29). MAIN OUTCOME MEASURES--Change in symptom scores determined with questionnaire; histological evidence of gastritis and microbiological evidence of presence of H pylori in biopsy specimens. RESULTS--Overall, H pylori was eradicated in 41 (49%) patients. Although gastritis scores improved significantly in only patients in whom H pylori had been eradicated (from 1.56 to 0.61, p less than 0.01 v from 1.83 to 1.07, p = 0.52) mean symptom scores after treatment were similar in patients in whom H pylori had or had not been eradicated (3.0 v 2.3, NS). Similarly the mean symptom score improved whether or not gastritis improved (2.8 v 3.1 respectively, p = 0.72). The observations were similar for treatment groups analysed individually. CONCLUSION--Antral infection with the organism does not seem to have an important aetiological role in non-ulcer dyspepsia short term.     

pH, healing rate, and symptom relief in patients with GERD

Gastroesophageal reflux symptoms are common and occur in all of us from time to time. In others, reflux may be associated with ulcerative esophagitis. The symptoms may be aggravated by large meals, coffee, smoking and position. Physiological and pathological reflux can be separated by the frequency and duration of the exposure of the lower esophagus to acid. Pathological reflux results in symptoms and also esophagitis and ulceration in some patients. Although gastroesophageal reflux disease (GERD) is considered to result from a disorder of motility in the esophagus, gastric acid and peptic activity are deemed pivotal to the initiation and continuation of the esophageal damage and the development of symptoms. Acid exposure in the esophagus is normally less than 4 percent of the 24 hours with a pH below 4. An increase over 4 percent of the time with a pH less than 4 is considered pathological. Hence, antisecretory drugs have become the principle approach to the treatment of reflux symptoms and esophagitis since they reduce the acidity, of gastric juice and the activity of pepsin. Importantly, they also reduce the volume of gastric juice available for reflux into the esophagus. There is a clear relationship between the degree and duration of acid suppression and the relief of heartburn and healing of esophagitis. Pharmacodynamic studies with different dose regimens of the H2-receptor antagonists and the proton pump inhibitors show a difference in the degree and duration of the antisecretory effect, and this correlates closely with the results of clinical trials with respect to the healing of esophagitis and the relief of symptoms. Proton pump inhibitors achieve healing rates by week four, which are not achieved by H2-receptor antagonists even after 12 weeks of treatment. The advantage of proton pump inhibitors over H2-receptor antagonists is due to the greater degree, longer duration of effect and more complete inhibition of acid secretion that maintains intragastric pH above 4 for a maximal duration. Although there is no significant difference between proton pump inhibitors with respect to healing of esophagitis, symptom relief occurs earlier with lansoprazole than omeprazole, and this is probably due to the greater oral bioavailability and faster onset of action of lansoprazole when compared to omeprazole.     

Visual Evoked Response in Diagnosis of Multiple Sclerosis

The diagnostic value of the pattern-evoked response has been assessed in 73 patients referred because of suspected multiple sclerosis. Altogether 52 had delayed responses. Fifty-one patients in the group satisfied McAlpine''s criteria for diagnosing definite, probable, or possible multiple sclerosis. Of these, all but two had delayed responses in one or both eyes, while only three of the remaining 22 patients had delays. In those patients with multiple sclerosis but without any history of optic neuritis the incidence of delayed responses was only slightly less. Of 51 patients with delayed responses 23 had normal discs. Thus subclinical lesions of the visual pathways can be readily detected with this test. The high incidence of abnormal pattern responses, even in patients with no other ocular signs or symptoms, suggests that the test is of value in establishing the diagnosis.     

公英益胃汤联合四联疗法对慢性胃炎的治疗效果及对幽门螺旋杆菌感染的影响

摘要 目的：分析感染幽门螺旋杆菌（Hp）的慢性胃炎患者在接受治疗时应用公英益胃汤+四联疗法后对疗效的影响。方法：随机将80例我院诊治的Hp阳性的慢性胃炎患者分为对照组与实验组,每组40例,对比两组患者的治疗效果、两组患者治疗前后症状评分、两组患者症状缓解时间、Hp清除率及复发率、两组患者不良反应发生率。结果：实验组患者的治疗总有效率为97.50 %,对照组患者的治疗总有效率为77.50%,实验组治疗有效率较对照组高（P＜0.05）;治疗前两组患者的上腹疼痛、反酸、嗳气、食后胀满各项症状积分差异无统计学意义（P＞0.05）,治疗后两组患者的上腹疼痛、反酸、嗳气、食后胀满各项症状积分均降低,并且治疗后实验组患者以上症状评分均低于对照组治疗后（P＜0.05）;实验组患者腹部隐痛、食欲不佳、反酸缓解时间均较对照组短（P＜0.05）;两组不良反应发生率无差异（P＞0.05）;实验组患者的HP根除率高于对照组,复发率低于对照组（P＜0.05）。结论：公英益胃汤+四联疗法对于减轻Hp感染的慢性胃炎患者临床症状,促进其病情在短时间内得到缓解有着显著的疗效,同时这一治疗方案也能够有效清除患者体内的幽门螺旋杆菌,避免疾病的反复发作,降低疾病复发率,且不良反应较少,能够保证患者的用药安全。     

基于胃肠道表现就诊的婴儿牛奶蛋白过敏症临床分析

目的:探讨以胃肠道表现为首发症状的婴儿牛奶蛋白过敏症(cow milk protein allergy,CMPA)的临床特点,以减少误诊。方法:选择2012年7月至2015年6月我院消化门诊就诊的448例诊断为婴儿牛奶蛋白过敏患儿,采用问卷调查法收集临床资料和应用COMi SS症状评分法进行症状量化评估。结果:448例患儿中男216例,女232例,以0~6个月发病年龄为主。不同胃肠道首发症状就诊中腹泻50%,便血29%,反流或呕吐9%,阵发性哭闹7%,便秘5%。治疗前COMi SS评分均值10.24±2.60分,饮食回避2~4周后评分均值为3.68±1.17分,均值差6分。调查既往诊疗中误诊病例296例,不同胃肠道首发症状患儿的误诊率为:腹泻组71%,便血组68%,阵发性哭闹组50%,反流或呕吐组40%,便秘组66%。既往误诊病例中抗生素使用率达62%。误诊病例中发生营养不良112例,非误诊病例中营养不良4例,差异具有统计学意义(P0.05)。结论:胃肠型婴儿牛奶蛋白过敏主要症状为腹泻及便血。因症状缺乏特异性,临床实践中误诊发生率高。COMi SS症状评分法有助于临床医师对该病首发症状的识别和疗效观察。     

两个亨廷顿舞蹈病家系IT15基因的研究

为了探讨亨廷顿舞蹈病家系患者的临床特征与IT15基因中(CAG)_n重复拷贝数之间的相互关系, 对两家系患者的临床、影像学特征、发病年龄及遗传方式等进行分析; 用聚合酶链反应技术、6%聚丙烯酰胺凝胶电泳及直接测序等方法, 对42名家系成员的IT15基因的(CAG)_n三核苷酸重复序列进行分析。结果显示家系1患者无典型的临床“三联症”及尾状核的萎缩, 18名家系成员中9名患者IT15基因的(CAG)_n拷贝数介于40~50次之间,拷贝数与发病年龄无明显相关; 而家系2患者具有典型的“三联症”和尾状核的萎缩, 24名家系成员中5例患者(CAG)_n拷贝数大于等于50次, 发病年龄与(CAG)_n拷贝数相关。因此亨廷顿舞蹈病患者的临床特征在一定程度上受IT15基因的(CAG)_n三核苷酸重复拷贝数的影响, 拷贝数大于50次, 发病年龄与(CAG)_n拷贝数相关, 并有经父系遗传的(CAG)_n拷贝数的扩展, 且存在遗传早现现象。     

Characterization of Digestive Involvement in Patients with Chronic T. cruzi Infection in Barcelona,Spain

Background

Digestive damage due to Chagas disease (CD) occurs in 15–20% of patients diagnosed as a result of peristaltic dysfunction in some endemic areas. The symptoms of chronic digestive CD are non-specific, and there are numerous confounders. Diagnosis of CD may easily be missed if symptoms are not evaluated by a well trained physician. Regular tests, as barium contrast examinations, probably lack the necessary sensitivity to detect early digestive damage.

Methods

71 individuals with T. cruzi infection (G1) and 18 without (G2) coming from Latin American countries were analyzed. They were asked for clinical and epidemiological data, changes in dietary habits, and history targeting digestive and cardiac CD symptoms. Serological tests for T. cruzi, barium swallow, barium enema, an urea breath test, and esophageal manometry were requested for all patients.

Principal findings

G1 and G2 patients did not show differences in lifestyle and past history. Fifteen (21.1%) of G1 had digestive involvement. Following Rezende criteria, esophagopathy was observed in 8 patients in G1 (11.3%) and in none of those in G2. Manometry disorders were recorded in 34 G1 patients and in six in G2. Isolated hypotensive lower esophageal sphincter (LES) was found in sixteen G1 patients (23.9%) and four G2 patients (28.8%). Achalasia was observed in two G1 patients. Among G1 patients, ineffective esophageal motility was seen in six (five with symptoms), diffuse esophageal spasm in two (one with dysphagia and regurgitation), and nutcracker esophagus in three (all with symptoms). There were six patients with hypertonic upper esophageal sphincter (UES) among G1. Following Ximenes criteria, megacolon was found in ten G1 patients (13.9%), and in none of the G2 patients.

Conclusions

The prevalence of digestive chronic CD in our series was 21.1%. Dysphagia is a non-pathognomonic symptom of CD, but a good marker of early esophageal involvement. Manometry could be a useful diagnostic test in selected cases, mainly in patients with T. cruzi infection and dysphagia in whose situation barium swallow does not evidence alterations. Constipation is a common but non-specific symptom that can be easily managed. Testing for CD is mandatory in a patient from Latin America with constipation or dysphagia, and if diagnosis is confirmed, megacolon and esophageal involvement should be investigated.