Sensitivity of Serum Tissue Transglutaminase Antibodies for Endomysial Antibody Positive and Negative Coeliac Disease

Background: Serum antibodies to tissue transglutaminase (tTGA) are reported to have high sensitivity and specificity for coeliac disease and to correlate closely with endomysial antibodies (EmA). We assessed their performance in a coeliac population with a high proportion of EmA-negative patients, who have been under-represented in previous studies. Methods: We used a commercial ELISA kit to test for IgA class tTGA in sera from a population of 73 untreated coeliac patients with normal serum IgA and a high percentage (19%) EmA-negative, taking 58 patients with normal duodenal biopsies as controls. EmA was measured using indirect immunofluorescence. Results: Forty-six (63%) patients with villous atrophy (VA) had both tTGA and EmA. However, when considered separately, sensitivities of tTGA and EmA for VA were similar (75% versus 81%) and both had high specificity (98% versus 97%). As 9 patients were tTGA-positive only and 13 had EmA only, selection of patients for biopsy on the presence of either antibody would have had a sensitivity of 93% (68 of 73), with 5 (7%) patients seronegative for both. Conclusion: Although the ELISA tTGA assay is more convenient than EmA testing, it offers no advantages in sensitivity or specificity if used in isolation. However, incomplete concordance between EmA and tTGA positivity means that combination screening with both assays offers higher sensitivity, as almost a third of patients have only one antibody. As some coeliac patients with normal serum IgA are negative for both antibodies, biopsies should still be performed in seronegative individuals deemed at high risk for coeliac disease.     

On the Prevalence of Adult Coeliac Disease in Sweden

The occurrence of coeliac disease has been less recognized among adults than in children. We have examined the prevalence of adult coeliac disease in a defined population in Sweden, on the basis of results obtained during 7 years' gastroenterological routine practice. On 1 July 1979, the overall prevalence rate was found to be 58/100, 000 (1:1700). The age-adjusted rates were unevenly distributed. The peak rate, 130/100, 000 (1:750), appearing in the age interval of 45–54 years, indicates that unrecognized middle-aged coeliacs are not symptom-free and that they can be found in routine practice. Our peak rate of coeliac disease unaccompanied by dermatitis herpetiformis is in the same range as the rate found in Swedish children.     

The Diagnostic Value of Fasting Serum Total Bile Acid Concentration in Patients with Suspected Liver Disease

To assess the diagnostic value of fasting serum total bile acids (STBA) in liver disease, STBA together with serum bilirubin (BIL), serum alkaline phosphatase (AP), and serum aspartate aminotransferase (ASAT) were measured in 66 consecutive patients who had a liver biopsy. Twenty-four of the patients who had normal liver histology all had normal STBA values (< 8 μmol/l). In the remaining 42 patients with abnormal liver histology STBA values were elevated in 21, corresponding to a sensitivity of 0.50. The same figures for BIL, AP, and ASAT were 0.52, 0.76, and 0.79, respectively. The predictive values of elevated (PV_pos) and normal (PV_neg) STBA for disclosing or excluding liver disease, respectively, were not better than the figures for BIL, AP, and ASAT. None of the tests were suited for distinguishing among various liver diseases. It is concluded that STBA had no diagnostic advantage as compared with the commonly used liver function tests BIL, AP, and ASAT.     

Inhibitory Potency of Twice-a-Day Omeprazole on Gastric Acidity Is Enhanced by Eradication of H. pylori in Duodenal Ulcer Patients

The gastric pH-elevating effect of proton pump inhibitors such as omeprazole has been reported to be greater in the presence than in the absence of an H. pylori infection. It is unknown if this effect persists when a higher dose of omeprazole is taken. We undertook both 24-hr pH-metry and 24-hr aspiration studies in 12 H. pylori-positive patients with a history of duodenal ulcer (DU); (1) when not on omeprazole; (2) when on omeprazole 20 mg twice a day for 8 days; (3) two months after eradication of H. pylori and when not on omeprazole; and (4) after eradication of H. pylori and when on omeprazole twice a day. Eradication of H. pylori in DU results in lower mean and median pH; decreased percent pH q 3/ 4, and greater median H⁺ after breakfast, after lunch, and overnight; and omeprazole appears to have less of a pH-elevating effect in the absence than in the presence of an H. pylori infection. The fall in gastric juice NH₃ concentration as a result of eradicating H. pylori partially explained the lower pH-elevating effect of omeprazole. The variation in acid inhibitory effect of omeprazole after as compared with before eradication of H. pylori could not be explained by differences; (1) in gastric juice concentrations of IL-1, IL-8, IL-13, or epidermal growth factor; (2) in the fasting or fed total concentration of gastric juice bile acids; (3) in the fasting concentrations or area under-the-curve (AUC) of the gastric H⁺ concentrations in response to food; or (4) in the pharmacokinetics of omeprazole. The difference in H⁺ AUC without omeprazole minus with omeprazole was actually greater when compared after versus before eradication of H. pylori. Thus, in DU the pH-elevating potency of omeprazole taken twice a day is greater in the presence than in the absence of an H. pylori infection.     

Dynamic Position Testing for the Detection of Esophageal Acid Reflux Disease

Currently the most widely accepted study for the detection of significant esophageal reflux disease is the 24-hr pH study. It is a problematic study, however. The data obtained from that study have to be analyzed by comparison to a normal tested population, revalued through a weighted scale, then judged against recorded symptoms in order to obtain a valid interpretation. Dynamic position acid reflux testing has recently been described as a better alternative. In this comparative study between dynamic position and 24-hr pH testing in 64 patients, the dynamic position study was found to be more definitive, more informative, and more efficient in the detection of significant esophageal acid reflux disease.     

Effect of Cigarette Smoking on Duodenogastric Reflux of Bile Acids*

Abstract: The possibility that smoking induces duodenogastric reflux was examined in 13 healthy male volunteers. Gastric juice was aspirated for four consecutive 20-minute periods, and reflux quantitated by measuring total bile acids (TBA), chenodeoxycholic acid (CDCA) and glycocholic acid (GCA) in the juice. One cigarette was smoked during either period 2 or period 3. Amounts of bile acids (μmoles; means ±SEM) refluxing into stomach during the pre-smoking, smoking, and post-smoking periods respectively were: TBA—4.5 ± 1.1, 5.4 ± 3.0 and 3.9 ± 1.6; CDCA— 1.7 ± 0.6, 1.5 ± 0.9 and 2.0 ±1.1; GCA—1.8 ± 1.7, 1.1±0.6 and 1.0 ± 0.6. Paired analysis revealed no significant effect of smoking on any of these parameters. These findings, based on quantitative methods, do not confirm those of previous unblinded and semiquanti-tative studies. We conclude that smoking one cigarette does not provoke duodenogastric reflux.     

Prevalence of Coeliac Disease in the General Population of Northern Spain: Strategies of Serologic Screening

Background: Coeliac disease (CD) is common in Western countries. In Spain, however, no studies exist on its prevalence. The best method for serologic screening is also unknown. Methods. We determined the IgA and IgG antigliadin antibodies (AGA) and IgA antiendomysium antibodies (AEA) in a sample of 1170 randomly selected subjects from a health area in northern Spain. The prevalence of CD was calculated with a two-step serologic screening method (first IgA and IgG AGA and then AEA in those positive for AGA) or with only one step with AEA determination. Diagnosis was confirmed by small-intestinal biopsy. Results: When using a two-step strategy, we found 174 (15%) subjects with AGA. Only one of these was confirmed by means of AEA (prevalence of CD = 0.9/1000). Two subjects were found to be positive when a one-step strategy was used (prevalence of CD = 1.7/1000). This yielded an economic saving of 19% with regard to the use of a two-step strategy. One new case of CD in a seronegative subject was diagnosed during the study (real prevalence of CD = 2.6/1000; 95% confidence interval = 0.7-8.2). Conclusions: The prevalence of CD in Northern Spain is 2.6/1000 (1:389). One-step serologic screening (AEA) is both more economical and more sensitive than the two-step procedure (first AGA and then AEA if AGA is positive).     

Serum bile acids, programmed cell death and cell proliferation in the mucosa of patients with colorectal adenomas

BACKGROUND: Deoxycholic acid induced programmed cell death and an imbalance with cell proliferation may favour colorectal tumourigenesis according to 'in vitro' studies, but information is lacking on the relationships occurring 'in vivo' in humans. AIMS: To evaluate whether serum deoxycholic acid is associated with programmed cell death and cell proliferation in colonic mucosa. METHODS: In 10 patients with colorectal adenomas, we measured fasting serum levels of bile acids; and, in normal colonic mucosa, programmed cell death by the TUNEL technique and cell proliferation by immunohistochemical staining with anti-Ki67. Total and compartmental indices for both activities were calculated. RESULTS: Among serum bile acids, only total deoxycholic acid (median: 0.89 micromol/L +/- 0.54 95% CI), showed a significant positive correlation with the total and basal compartments PCD Index (r = 0.68, p < 0.05). Total proliferation index showed no correlation with either total PCD Index, or bile acids. Within the median compartment of the crypt, cell proliferation was negatively associated with all unconjugated bile acids. CONCLUSIONS: The positive association between deoxycholic acid and programmed cell death in the basal compartment of the crypt, and the negative association of cell proliferation and unconjugated bile acids in the median compartment, do not seem to support the co-carcinogenic effect of deoxycholic acid.     

缩短禁饮时间对胃食管反流合并症患者麻醉风险及术后影响的研究

目的探讨缩短禁饮时间对胃食管反流合并症患者术前麻醉风险,以及其他术后恢复情况的影响。 方法选取2019年1月至2019年12月,新疆维吾尔自治区人民医院微创外科、肝胆外科胆囊疾病合并胃食管反流病择期行腹腔镜胆囊切除术患者176例,按照术前不同的禁饮时间将纳入研究的患者用随机数字表随机分为A、B、C、D组,各组分别为44例,各组的禁饮时间依次为3 h、4 h、5 h、6 h,术前利用胃部超声评估不同禁饮时间的麻醉风险。 结果术前胃部超声检查结果,4组差异无统计学意义（均P＞0.05）,且均符合麻醉要求,未发生反流误吸。术后停止输液及住院时间,A、B组明显短于C、D组（P＜0.05）,住院费用A组少于D组（P＜0.05）;术后恶心发生情况4组比较结果显示,A、B组显著少于C、D组（P＜0.05）,但是4组之间呕吐差异无统计学意义（P＞0.05）。 结论胆囊疾病合并胃食管反流患者缩短术前禁饮时间是安全可行的,超声结果显示均符合麻醉要求,没有增加患者的麻醉风险,还可以减少患者术后输液时间,降低住院时间,减轻患者的经济负担。     

Role of gut microbiota,bile acids and their cross‐talk in the effects of bariatric surgery on obesity and type 2 diabetes

Type 2 diabetes mellitus is becoming increasingly prevalent worldwide, and has become one of the greatest threats to global health. Bariatric surgery was initially designed to achieve weight loss, and subsequently was noted to induce improvements or remission of type 2 diabetes. Currently, these bariatric operations, such as Roux‐en‐Y gastric bypass and sleeve gastrectomy, are the most effective procedures for the treatment of obesity and type 2 diabetes mellitus worldwide. However, the specific mechanism mediating the beneficial effects of metabolic surgery has remained largely unknown. Those mechanical explanations, such as restriction and malabsorption, are challenged by accumulating evidence from human and animal models of these procedures, which points to the weight‐independent factors, such as hormones, bile acids, gut microbiota, nervous system and other potential underlying mechanisms. A growing body of evidence suggests that gut microbiota are associated with the development of several metabolic disorders, and bile acids and FXR signaling are important for the metabolic benefits of bariatric surgery. Given the close relationship between bacteria and bile acids, it is reasonable to propose that microbiota–bile acid interactions play a role in the mechanisms underlying the effects of metabolic surgery.     

胃食管反流检查方法对胃食管反流病的诊断价值

评估不同的诊断方法在胃食管反流病诊断中的价值。对135全角典型胃食管反流症状,并经内镜证实有下段食管炎的患者X线钡餐确定反流,核素显像测定反流,24小时食管内pH监测,LESP测定及Losec实验性治疗。结果显示：X线钡餐检查27例,9例阳性,阳性率为30．3％,核素显像9例,7例阳性,阳性率77．7％;食管内24小时pH监测72例,53例阳性,阳性率73．61％;LESP测定25例,10例阳性,阳性率40％;56例行Losec试验性治疗,有效54例,阳性率96．4％。本研究结果表明：在所有的检查方法中,Losec试验性治疗阳性率最高,且不需特殊设备及操作技能,可作为临床上诊断本病的有效方法。食管内24小时pH 和核素显像测定胃食管反流阳性率近似,但后者设备昂贵,仅适用于有胃食管反流疾病的儿童,食管内24小时pH监测敏感性高,不失为诊断胃食管反流疾病的可靠指标。     

胆道良性疾病致胆汁反流对胃运动的影响及机制探讨

目的观察良性胆道疾病致胆汁反流对胃运动的影响，并同步观察某些相关胃肠激素水平的变化，初步探讨其可能的机制。方法采用B超确立试验组患者为胆道良性疾病，同时设立健康对照组。采用B超、胃电测定的方法，测定各组胃运动功能；采用胃镜检查并抽取胃液，测定胆汁酸浓度确定胆汁反流；同步抽取患者和健康人空腹静脉血，测定血浆胃动素（motilin，MTL）、胆囊收缩素（cholecystokinin，CCK）水平，并检测胃窦部黏膜中一氧化氮（NO）水平。结果良性胆道疾病患者胆汁反流发生率显著升高，与对照组比较差异有统计学意义（P〈0．05）；胆汁反流患者较无反流者胃肌电正常慢波百分比、主频及振幅显著降低（P〈0．05）；胃排空时间、胃窦收缩频率及胃排空速率存在显著差异（P〈0．05）；胆汁反流患者胃窦黏膜组织NO较无反流者显著增高（P〈0．05），而胆汁反流患者空腹血浆中MTL水平显著降低（P〈0．05）；良性胆道疾病患者空腹血浆CCK与正常组比较无明显差异（P〉0．05）。结论良性胆道疾病致胆汁反流患者存在胃肌电紊乱及胃排空延缓，其原因可能与胆道疾病所致某些胃肠道激素水平变化存在密切关系。     

Influence of intraduodenal chenodeoxycholic acid on secretory and pressure activity of the stomach and duodenum

The influence of duodenal infusion of bile acid at a concentration similar to that in the common bile-duct (50 mmol/1) on antroduodenal motility, duodenogastric reflux, gastric and duodenal secretion was studied in 10 healthy volunteers. Intraluminal pressures were recorded in the antrum and the first and second parts of the duodenum. Gastric and distal duodenal contents were collected by continuous low pressure sump aspiration during infusion of either saline or chenodeoxycholic acid (CDC) into the second part of the duodenum. Values for duodenogastric reflux and gastric and duodenal secretion were calculated with reference to the recovery of two non-absorbable markers infused into the stomach and second part of the duodenum. Each volunteer received at least 3 h of saline infusion and 2 h of CDC infusion. During saline infusion, duodenogastric reflux varied with the migrating motor complex (MMC), being statistically greater at the end of duodenal phase III activity than at other times (P<0.05). Infusion of CDC abolished the MMC and inhibited antral contractions but the amount of reflux was not increased compared with the saline period. Infusion of CDC also produced marked increases in measured bicarbonate (P<0.001), trypsin (P<0.001), phospholipase A₂ (P<0.05) and endogenous total bile acid (P<0.05) in the duodenum, although gastric acid secretion was unaffected. These findings suggest that bile acid may regulate gastroduodenal motor activity and pancreaticobiliary secretion.     

The Usefulness of the Measurement of Esophagogastric Junction Distensibility by EndoFLIP in the Diagnosis of Gastroesophageal Reflux Disease

Background/AimsIncreased esophagogastric junction (EGJ) relaxation is the most important mechanism involved in gastroesophageal reflux disease (GERD). An endoscopic functional luminal imaging probe (EndoFLIP^Ⓡ) is a device used to quantify EGJ distensibility in routine endoscopy. The aim of the current study was to assess the usefulness of EndoFLIP^Ⓡ for the diagnosis of GERD compared to normal controls.MethodsWe analyzed EndoFLIP^Ⓡ data from 204 patients with erosive reflux disease (ERD), 310 patients with nonerosive reflux disease (NERD), and 277 normal subjects. EndoFLIP^Ⓡ uses impedance planimetry to measure 16 cross-sectional areas (CSAs) in conjunction with the corresponding intrabag pressure within a 4.6 cm cylindrical segment of a fluid-filled bag. The EGJ distensibility was assessed using 40 mL volume-controlled distensions.ResultsThe mean distensibility index values were 13.98 mm²/mm Hg in ERD patients, 11.42 mm²/mm Hg in NERD patients, and 9.1 mm²/mm Hg in normal subjects. There were significant differences in EGJ distensibility among the three groups (p<0.001). In addition, the CSAs were significantly higher in the ERD (291.03±160.77 mm²) and NERD groups (285.87±155.47 mm²) than in the control group (249.78±144.76 mm², p=0.004). We determined the distensibility index cutoff value of EGJ as 10.95 for the diagnosis of GERD by receiver operating characteristic curve analysis.ConclusionsThe EGJ distensibilities of GERD patients were higher than those of normal subjects, regardless of the presence of reflux esophagitis. Thus, the measurement of EGJ distensibility using the EndoFLIP^Ⓡ system could be useful in the diagnosis of GERD.     

Prediction of the Severity of Rhesus Haemolytic Disease by Means of Antibody Titrations Performed on the AutoAnalyzer

Ante-natal sera containing anti-D and anti-C + D antibodies were titred on an AutoAnalyzer system and the results compared with the standard manual method. A good correlation was achieved in 526 samples from 191 pregnant women. It was found that an antibody level above that of 15 International Units indicated the need for amniocentesis. One case is described where a possible bromelin inhibitor was present in the serum. The question of the method of estimating and reporting anti-D antibody is discussed and it is concluded that until a more accurate method of measuring anti-D in micrograms is available, International Units should be used.     

Effect of cyclosporin A on the biliary excretion of cholephilic compounds in rats.

Cyclosporin A (CsA) is known to cause cholestasis. CsA is reported to competitively inhibit the transport of the substrates of the bile salt export pump (Bsep), multidrug resistance protein 2 (Mrp2) and P-glycoprotein (P-gp) in the canalicular membrane vesicles. However, the inhibitory effect of CsA on various substrates of the canalicular ATP-dependent transporters in vivo is unknown. Therefore, in the present study, the acute effect of CsA on the biliary excretion of the substrates of Bsep, Mrp2 and P-gp was examined under the same condition. Ten minutes after the intravenous administration of CsA (25mg/kg), the biliary excretion of various bile acids and organic anions and cations was studied. CsA decreased the biliary excretion of tracer amounts of taurocholate, leukotriene C(4), estradiol-17beta-glucuronide, pravastatin, vinblastine and erythromycin. In contrast, the biliary excretion of high doses of taurocholate and sulfobromophthalein was only slightly or not inhibited by CsA. In conclusion, CsA may competitively inhibit biliary excretion of substrates of Bsep, Mrp2 and P-gp also in vivo, and CsA is considered to inhibit bile acid-dependent bile flow by the competitive inhibition of the canalicular transport of bile acids by Bsep.     

Effects of Diabetes and Hyperglycemia on Disaccharidase Activities in the Rat

Background and Methods: To elucidate the effect of hyperglycemia on disaccharidase activities, the specific and total activities of the disaccharidases were measured in the intestinal mucosa and kidney cortex of diabetic and hyperglycemic rats. The diabetes was induced with an intraperitoneal injection of streptozotocin (60 mg/kg). The rats were made hyperglycemic with an intravenous instillation of a solution containing 40% dextrose monohydrate at a rate of 1.5 ml/h for 24 h. Results:     

The Effect of Retinoic Acid and Deoxycholic Acid on the Differentiation of Primary Human Esophageal Keratinocytes

The mechanism linking gastroduodenal reflux disease to intestinal metaplasia in the esophagus (Barrett’s esophagus) has not been determined. Active conjugate metabolites of retinoic acid, in addition to bile acids, undergo an enterohepatic circulation in bile. Retinoic acid and bile acids are candidate mediators of keratinocyte transdifferentiation in Barrett’s esophagus. We studied the effects of retinoic acid on the differentiation of primary human esophageal keratinocytes cultured in vitro. Retinoic acid induces expression of a marker of intestinal differentiation, MUC2, in these cells. However, retinoic acid, alone or in combination with the hydrophobic bile acid, deoxycholic acid, does not affect esophageal keratinocyte squamous differentiation as assessed by involucrin expression and cellular morphology. The ability of retinoic acid to induce MUC2 expression may be relevant to the pathogenesis of Barrett’s esophagus. However, this does not result in suppression of squamous differentiation.     

Influence of physical factors on the development of gastroesophageal reflux in man: Analysis by means of an experimental mechanical model

In this paper, the isolated influence of physical factors on the development of gastroesophageal reflux in man is analyzed by means of a mechanical model. We evaluate the influence of gravity, intraabdominal presure, intrathoraci pressure, transmission of intraabdominal pressure to the high pressure zone, filling volume of the stomach, and the existence of a high pressure zone on the appearance of gastroensophageal reflux. PH-metry is used to record the episodes of reflux in the model. We wish to demonstrate the importance of gravity and intraabdominal pressure in the production of reflux. Intrathoracic pressure acts as an antireflux mechanism only when associated with a zone of high pressure. The intraabdominal pressure may be transmitted to the high pressure zone as a purely mechanical effect and the greater gastric filling volume may, when associated with the intraabdominal pressure, facilitate reflux without physical changes in the high pressure zone (the equivalent of a reduction in the length of the lower esophageal sphincter in man). We conclude that this model may help to explain the influence of the physical factors mentioned above on the development of gastroesophageal reflux in man.     

旋毛虫病患者血清中循环抗原及抗体检测的研究

111例旋毛虫病患者用斑点ELISA 试验检测循环抗原(CAg),薄板ELISA试验检测特异性抗体。其中未经治疗的患者36例,两法检出率均为100％;75例经治疗后3个月的患者血清中CAg 检出率为78.67％,抗体 IgG为 97.47％、IgM为 84.82％,IgE为 83.54％,两组间的 CAg、特异性 IgM、IgE抗体都有明显差异。健康人血清、日本血吸虫病患者血清试验,均有一定的假阳性与交叉反应。斑点ELISA检测旋毛虫病患者血清中CAg,ELISA检测IgM、IgE仍属敏感的和特异的,并且重现性好。特别是斑点ELISA采用第一和第二抗体标记酶进行两次放大的方法比之选用生物素亲和素放大法价廉,易于制备,从而可以取代传统的活检法,具有实用价值。