Abstract: Splanchnic artery stenosis is common and mostly asymptomatic and may lead to gastrointestinal ischemia (chronic splanchnic syndrome, CSS). This study was designed to assess risk factors for CSS in the medical history of patients with splanchnic artery stenosis and whether these risk factors can be used to identify patients with high and low risk of CSS.
Abstract: Gastrointestinal (GI) symptoms during exercise may be caused by GI ischaemia. The authors report their experience with the diagnostic protocol and management of athletes with symptomatic exercise-induced GI ischaemia. The value of prolonged exercise tonometry in the diagnostic protocol of these patients was evaluated.
Abstract: The distribution of cardiovascular risk factors in patients with chronic gastrointestinal ischemia due to atherosclerosis of the splanchnic vessels (chronic splanchnic syndrome) is not well studied. The aim of this study was to determine the cardiovascular risk factor pattern in patients with chronic splanchnic syndrome.
Abstract: Patients with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors.
Abstract: Treatment of chronic splanchnic syndrome remains controversial. In the past 10 years, endovascular repair (ER) has replaced open repair (OR) to some extent. This evidence summary reviews the available evidence for ER or OR of chronic splanchnic syndrome.
Abstract: Chronic gastrointestinal ischemia (CGI) is still a difficult diagnosis to make. Currently, the only diagnostic with an acceptable sensitivity for actual mucosal ischemia is gastrointestinal tonometry. However, tonometry is a cumbersome and invasive diagnostic test. We are in need of a more simple, noninvasive test for diagnosing mucosal ischemia. A sensitive and early serum marker could be of great use in this setting. The aim of this study was to evaluate the use of promising serum markers for mucosal ischemia [intestinal fatty acid binding protein (I-FABP), D-lactate, and lipopolysaccharide] and compared findings with corresponding gastrointestinal tonometry measurements.
Abstract: Celiac artery compression syndrome (CACS) can be treated successfully by division of the median arcuate ligament and celiac plexus fibers. The standard technique is the open approach by an upper midline or left subcostal incision. Only six single cases in which a laparoscopic transabdominal approach for CACS was used have been reported. We prospectively evaluated the feasibility of the endoscopic retroperitoneal approach for treatment of CACS.
Abstract: Gastrointestinal tonometry is currently the only clinical diagnostic test that enables identification of symptomatic chronic gastrointestinal ischemia. Gastric exercise tonometry has proven its value for detection of ischemia in this patients group, but has its disadvantages. Earlier studies with postprandial tonometry gave unreliable results. In this study we challenged (again) the use of postprandial tonometry in patients suspected of gastrointestinal ischemia.
Abstract: Splanchnic or gastrointestinal ischemia is rare and randomized studies are absent. This review focuses on new developments in clinical presentation, diagnostic approaches, and treatments. Splanchnic ischemia can be caused by occlusions of arteries or veins and by physiological vasoconstriction during low-flow states. The prevalence of significant splanchnic arterial stenoses is high, but it remains mostly asymptomatic due to abundant collateral circulation. This is known as chronic splanchnic disease (CSD). Chronic splanchnic syndrome (CSS) occurs when ischemic symptoms develop. Ischemic symptoms are characterized by postprandial pain, fear of eating and weight loss. CSS is diagnosed by a test for actual ischemia. Recently, gastro-intestinal tonometry has been validated as a diagnostic test to detect splanchnic ischemia and to guide treatment. In single-vessel CSD, the complication rate is very low, but some patients have ischemic complaints, and can be treated successfully. In multi-vessel stenoses, the complication rate is considerable, while most have CSS and treatment should be strongly considered. CT and MR-based angiographic reconstruction techniques have emerged as alternatives for digital subtraction angiography for imaging of splanchnic vessels. Duplex ultrasound is still the first choice for screening purposes. The strengths and weaknesses of each modality will be discussed. CSS may be treated by minimally invasive endoscopic treatment of the celiac axis compression syndrome, endovascular antegrade stenting, or laparotomy-assisted retrograde endovascular recanalization and stenting. The treatment plan is highly individualized and is mainly based on precise vessel anatomy, body weight, co-morbidity and severity of ischemia.
Abstract: In most patients with chronic splanchnic syndrome the celiac artery is involved, enabling the use of gastric exercise tonometry as a diagnostic function test. In this study, we investigated the feasibility of combining gastric and jejunal exercise tonometry and determined the normal values. We investigated the potential diagnostic value of combining gastric with jejunal exercise tonometry.
Abstract: To assess the prevalence, risk factors and timing of gastrointestinal (GI) complaints in a large group of runners competing in a long-distance run. GI symptoms indicating GI ischaemia were of specific interest.
Abstract: Gastrointestinal (GI) symptoms are reported by up to 70% of endurance athletes. Although exercise leads to decreased gastrointestinal blood flow, GI-ischaemia is rarely reported as a cause. Mucosal ischaemia may result in nausea, abdominal cramps and bloody diarrhoea. After exercise, reperfusion damage and endotoxaemia may cause systemic symptoms as well. In three patients, two women aged 46 and 25 respectively and a man aged 40, with a heterogeneous presentation of exercise induced GI-symptoms, GI-ischaemia was demonstrated using gastric exercise tonometry. Gastric tonometry is mandatory for the diagnosis and follow-up. In the first patient, an isolated celiac artery stenosis was found; after incision of the left crus of the diaphragm, she was asymptomatic and the results of gastric tonometry improved. The other two patients had non-occlusive ischaemia associated with high exercise intensity. Reduction of the exercise intensity resulted in the complaints disappearing.
Abstract: Gastrointestinal ischemia is always accompanied by an increased luminal CO(2). Currently, air tonometry is used to measure luminal CO(2). To improve the response time a new sensor was developed, enabling continuous CO(2) measurement. It consists of a pH-sensitive hydrogel which swells and shrinks in response to luminal CO(2), which is measured by the pressure sensor. We evaluated the potential clinical value of the sensor during an in vitro and in vivo study.
Abstract: Gastric exercise tonometry is a functional diagnostic test in chronic gastrointestinal ischemia. As maximal exercise can cause false-positive tests, exercise buildup should be controlled to remain submaximal. We evaluated three parameters for monitoring and adjusting exercise levels (heart rate [HR], respiratory quotient [RQ], and serial lactate measurements) in 178 tests in both healthy volunteers and patients suspected of gastrointestinal ischemia. Exercise levels above submaximal occurred in 20% of HR-, 2% of RQ-, and 5% of lactate-monitored tests (P<0.05 for HR vs. RQ and lactate). Low levels were seen in 5% of HR-, 10% of RQ-, and 41% of lactate-monitored tests (P<0.01 for lactate vs. HR and RQ). High levels resulted in 43% false-positive tonometry results compared to 19% of all tests (P<0.001); low levels did not result in more false negatives (5% vs. 6%). Although RQ monitoring yielded the greatest proportion of optimal exercise tests, serial lactate monitoring is our method of choice, combining optimal diagnostic accuracy, low cost, and simplicity.
Abstract: Chronic gastrointestinal ischemia is still a difficult diagnosis to establish. The diagnosis depends on a high degree of clinical suspicion as well as selective angiography. Duplex sonography may serve as a screening tool, providing information on splanchnic vessel patency and flow patterns. GET is a minimally invasive test that can be used for diagnosis in patients with chronic gastrointestinal ischemia, and can differentiate between symptomatic and asymptomatic splanchnic artery stenosis. In the present study, we compared four different diagnostic approaches.
Abstract: We report a case of acute gastrointestinal ischemia during a very stressful event in whom the diagnosis was made by 24-hour tonometry. This case report unequivocally links a stressful event with increased catecholamine release and subsequent severe symptomatic gastrointestinal ischemia. The role of ischemia as potential pathophysiological mechanism has never been studied in detail. The clinical significance of finding such an association is underscored by this case report, where a vasoactive drug normally used for hypertension treatment resulted in greatly improved abdominal symptoms.
Abstract: Controversy continues about the mere existence of the celiac artery compression syndrome. Earlier results of treatment of unselected patients groups showed varying, mostly disappointing, results. The recently introduced gastric exercise tonometry test is able to identify patients with actual gastrointestinal ischemia. We prospectively studied the use of gastric exercise tonometry as a key criterion for revascularization treatment in patients with otherwise unexplained abdominal complaints and significant stenosis of the celiac artery by compression of the arcuate ligament.
Abstract: The clinical relevance of splanchnic artery stenosis is often unclear. Gastric exercise tonometry enables the identification of patients with actual gastrointestinal ischaemia. A large group of patients with splanchnic artery stenosis was studied using standard investigations, including tonometry.
Abstract: The normal pattern of carbon dioxide (CO2) levels in the human stomach and small bowel after meals is unknown. The intraluminal carbon dioxide level is a sensitive and early marker for organ mucosal ischemia. CO2 levels in both the stomach and small bowel are influenced by multiple factors other than adequacy of perfusion. Gastric acid production, salivary bicarbonate and CO2 produced or absorbed by meals are the disturbing variables. Prolonged gastric (and jejunal) tonometry after meals can be of additional value in the work-up of patients suspected of (chronic) gastrointestinal ischemia. The purpose of this study was to challenge these problems using in vitro tested meals and a rigid acid-suppression regimen in a group of healthy subjects.
Abstract: Future colorectal cancer (CRC) screening programmes should not (greatly) interfere with regular health care. Hence, we analysed the Dutch endoscopic practice to provide a clear insight into endoscopic workload and manpower with a special emphasis on the current ability to facilitate a successful implementation of a faecal occult blood test (FOBT)-based nationwide CRC screening programme.
Abstract: Microscopic colitis presents with chronic diarrhoea with or without abdominal pain. Microscopic colitis is an important cause of chronic diarrhoea. It can be distributed throughout the colon, as well as limited to the right colon. Microscopic colitis is associated with coeliac disease. We studied the prevalence and distribution of microscopic colitis in patients with diarrhoea and normal colonoscopy and we studied the association with coeliac disease.
Abstract: Chronic gastrointestinal ischemia or chronic splanchnic syndrome is a difficult diagnosis. The use of a physiologic test, combined with clinical and anatomic data, should improve diagnostic accuracy. This study evaluates the diagnostic accuracy and clinical impact of gastric tonometry during exercise (GET) in a patient cohort suspected of chronic splanchnic syndrome.
Abstract: The technical and clinical outcome of endovascular revascularization was analyzed in patients with suspicion of chronic splanchnic syndrome (CSS).
Abstract: Helicobacter pylori gastritis may progress to glandular atrophy and intestinal metaplasia, conditions that predispose to gastric cancer. Profound suppression of gastric acid is associated with increased severity of H pylori gastritis. This prospective randomised study aimed to investigate whether H pylori eradication can influence gastritis and its sequelae during long term omeprazole therapy for gastro-oesophageal reflux disease (GORD).
Abstract: Budesonide, a topical corticosteroid, has proven useful for the management of Crohn's disease. Its efficacy is similar to prednisone but it has fewer side effects. A new pH-modified release capsule (Budenofalk) is probably efficacious in distal ulcerative colitis. The aim of the present study was to establish the pharmacokinetics, pharmacodynamics, and safety of two dosage regimens of budesonide capsules and to obtain efficacy information. Budenofalk 9 mg daily was administered as a single dose 9 mg in 8 patients and as three 3 mg doses in 7 patients with active distal ulcerative colitis for 8 weeks. Symptoms were assessed at three timepoints during the study: baseline, 4 and 8 weeks after start of treatment. Endoscopic evaluation and budesonide concentration in mucosal biopsy specimens was performed at 0 and 8 weeks. A pharmacokinetic profile and pharmacodynamic profile (cortisol, lymphocytes and neutrophils) was performed at day 5. In the 9 mg o.d. group, higher peak concentrations and systemic availability was found compared to the 3 mg t.i.d. group. Cortisol suppression was more pronounced after 9 mg o.d. than after 3 mg t.i.d. Lag-time, AUC and pharmacodynamic effects were comparable (14% mean decrease lymphocyte count and 26% mean increase neutrophil count). Mucosal biopsy specimens in the distal colon revealed significant budesonide levels with both regimens. After 8 weeks, 71% in the 9 mg o.d. group and 38% in the 3 t.i.d. group responded. The endoscopic index improved from 10 +/- 2 to 2 +/- 3 (p <0.001) with 9 mg o.d. and from 9 +/- 2 to 4 +/- 4.7 (p = 0.02) with 3 mg t.i.d. The pharmacokinetic and pharmacodynamic profiles found in this study indicate that Budenofalk reaches the distal part of colon and rectum, but further studies to validate the budesonide assay in the mucosa and comparison with a control group are necessary. This limited study suggests that Budenofalk is effective in distal colitis and side effects are rare. Based on these observations a large clinical trial using 9 mg o.d. is indicated to confirm efficacy and assess further possible side effects.
Abstract: In the past, small-bowel biopsies for diagnosis of celiac disease were taken from the jejunum with a suction capsule, but nowadays most physicians take endoscopic biopsies from the distal duodenum. To validate that practice we compared the diagnostic yield of endoscopic duodenal biopsies with that of endoscopic jejunal biopsies. In addition, we describe a method of orienting biopsy specimens optimally.
Abstract: Stenotic disorders of the splanchnic arteries are not rare, and it is generally assumed that symptoms are rare in patients with a single splanchnic stenosis, and even in patients with multiple-vessel stenoses. Currently, only gastric exercise tonometry aids the diagnostic evaluation, as it indicates actual ischaemia. Patients with stenotic disorders without complaints are referred to as having chronic splanchnic disease (CSD) and those with ischaemic complaints as having chronic splanchnic syndrome (CSS). The classical presentation of CSS, including the triad postprandial pain, weight loss and upper abdominal bruit, is also known as 'intestinal angina'. From the experience of our multidisciplinary working team on gastrointestinal ischaemia in 110 patients with stenoses of at least one splanchnic artery, two different clinical patterns were observed. In our series approximately 60% of patients with single-vessel stenoses, including the coeliac artery compression syndrome, have CSS. They have fewer complications, very low mortality, but most can be successfully treated by stenting or surgical treatment. Patients with multivessel splanchnic stenoses have more classical ischaemic complaints. Progression to a bowel infarction was seen in 34%, and mortality was 21%, mostly from bowel or myocardial infarction. Treatment should be tailored based upon perioperative risk assessment and local vascular anatomy. This may consist of autologous arterial bypass of one or two vessels, preferably antegrade. stenting or a combination of both. This differentiation between single- and multivessel splanchnic disease has considerable consequences for optimal work-up and treatment.
Abstract: Non-occlusive mesenteric ischaemia is characterized by gastrointestinal ischaemia with normal vessels. In gastroenterology it is recognized as rare disease occasionally causing acute bowel infarction or ischaemic colitis. From intensive care literature this disorder is recognized as an early phenomenon during circulatory stress. This early mucosal ischaemia then leads to increased permeability, bacterial translocation, and further mucosal hypoperfusion. The damage is produced mainly during reperfusion following ischaemia with fresh inflow of oxygen and outflow of waste products into the systemic circulation. The mechanisms underlying non-occlusive mesenteric ischaemia include macrovascular vasoconstriction, hypoperfusion of the tips of the villi and shunting. It is very common in critically ill and perioperative patients, but also occurs in pancreatitis, renal failure and sepsis. Treatment options include aggressive fluid resuscitation and careful choice of vasoactive drugs. Control of reperfusion damage and new endothelin-antagonists are potentially useful new treatment options.
Abstract: Chronic inflammatory bowel disease (IBD) is characterised clinically by periods of well being interspersed by exacerbations of disease activity. Differentiation between IBD and less severe disorders such as irritable bowel syndrome requires invasive and expensive diagnostic procedures. Diagnostic differentiation between active disease, symptoms due to residual constriction of the fibrotic lumen and functional symptoms is a well-known problem. There are not yet any laboratory parameters with sufficient discrimination in terms of sensitivity and specificity. Colonoscopy and histopathological examination remain the gold standards: in Crohn's disease this may be complex due to the variable localisation of the inflammatory process. Abdominal scintigraphic procedures, although informative, are complex and expensive. The recent assessment of faecal calprotectin, a calcium- and zinc-binding anti-inflammatory protein found in neutrophilic granulocytes and monocytes, offers an attractive alternative as an index of intestinal inflammation. We measured this stable marker in random stool samples from 187 patients including healthy volunteers, patients with endoscopically classified active IBD or IBD in remission, and patients with other gastrointestinal disorders. Disease activity was monitored by clinical symptoms, blood tests and endoscopy. Our results confirm previous literature findings that faecal calprotectin is a promising and useful non-invasive tool in the screening of patients presenting with abdominal pain and diarrhoea. Moreover, calprotectin seems helpful in differentiating between active and non-active IBD and possibly also in the monitoring of disease activity.
Abstract: Various forms of vasculitis may result in mesenteric ischaemia, ischaemic colitis or aneurysm formation in the aorta or intestinal blood vessels. Vasculitides may involve large- and/or medium-sized vessels, medium- and/or small-sized vessels, or small-sized vessels only. It is essential to differentiate between the different forms of vasculitis since diagnostic tests and therapies differ greatly. Gastrointestinal manifestations of vasculitis can generally be detected using angiography, digital subtraction angiography and/or magnetic resonance angiography (MRA). Various laboratory tests are helpful in establishing the diagnosis in patients in whom vasculitis is clinically suspected. In addition, the diagnosis should be confirmed using histology or angiography if possible. Treatment of vasculitis not caused by chronic infection consists of high dose corticosteroids and, in the case of polyarteritis nodosa or vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA), cyclophosphamide.
Abstract: Colorectal cancer is the second most common cancer in the Netherlands. Its incidence rates are among the highest in Europe. In the past decades, a right-sided shift of the subsite location of colorectal cancer has been reported. These changes in anatomic distribution might have clinical implications for the use of diagnostic or screening tools for colorectal cancer. This study was designed to investigate the change in incidence and anatomic distribution of colorectal cancer in a population over a period of 15 years.
Abstract: Heavy physical exercise may cause gastrointestinal signs and symptoms, and, although splanchnic blood flow may decrease through redistribution by more than 50%, it is unclear whether these signs and symptoms relate to gastrointestinal ischemia. In 10 healthy volunteers, we studied the effect of exercise on gastric mucosal perfusion adequacy using air tonometry. Two relatively short (10 min) exercise stages were conducted on a cycle ergometer, aiming for 80 and 100% of maximum heart rate, respectively. The intragastric-arterial PCO(2) gradient (Delta PCO(2)) was elevated by 1.1 +/- 1.0 kPa over baseline values (-0.1 +/- 0.3 kPa) only after maximal exercise (P < 0.001). Delta PCO(2) positively correlated with the arterial lactate level taken as an index of exercise intensity (Spearman's rank test: r = 0.76, P < 0.0001). By bilinear regression analysis, a lactate level of 12 mmol/l, above which a sharp rise in the Delta PCO(2) occurred, was calculated. We conclude that, in healthy volunteers with normal splanchnic vasculature, gastric ischemia may develop during maximal exercise as judged from intragastric PCO(2) tonometry.
Abstract: The main cause of chronic gastrointestinal ischaemia is atherosclerosis. Stenotic lesions of the mesenteric circulation are relatively common, but lead to chronic ischaemic complaints due to collateral circulation in probably only 2-3 per 100,000 inhabitants per year. The classical presentation (post-prandial abdominal pain, weight loss, upper abdominal souffle) is present in a minority of patients only. Symptoms also occur after exercise. Gastric ulcers and diarrhoea are less frequent. Although patients with 2 and 3 vessel involvement (coeliac artery, superior mesenteric artery and inferior mesenteric artery) usually experience the most severe ischemic complaints, patients with single vessel involvement can also develop symptoms. In the diagnosis of cases with abdominal complaints, factors that aggravate or reduce the complaints anamnestically are the guideline for supplementary diagnostics. The more frequent causes of the symptoms are to be excluded first. Doppler-ultrasonography of the mesenteric vessels can detect most stenotic lesions accurately. To establish the diagnosis visceral angiography is needed. A new method of examination is magnetic resonance angiography (MRA). Another new method is tonometry during exercise: a PCO2 value in the lumen that is higher than that in the blood indicates ischaemia. Non-invasive treatment of chronic gastrointestinal ischaemia is aimed at reduction of the gastrointestinal metabolic workload by smaller meals, at suppression of acid secretion, at inhibition of the secretion of gastric acid and on risk factors for atherosclerosis.
Abstract: It has been suggested that admission to a gastroenterology service (GAS) is associated with a better prognosis and lower cost for treatment of gastrointestinal (GI) diseases, such as upper GI bleeding (UGB). However, a large potential bias by higher comorbidity on internal medicine services (MED) could not be excluded from these studies. We therefore compared patients with upper GI bleeding admitted to a gastroenterology or internal medicine department, with special emphasis on prognostic factors, such as comorbidity, and outcome.
Abstract: Gastrointestinal luminal tonometry is a minimally invasive technique for measuring gastrointestinal ischaemia. Mucosal ischaemia leads to excessive production of tissue CO2 and thus to an increase of luminal PCO2. For this measurement, a nasogastric catheter is introduced with at its end a balloon permeable for CO2, this balloon is filled with air or liquid. After CO2 has diffused from the tissue into the lumen of the balloon, the PCO2 in the liquid or air is determined. Due to uncertainties about physiological background, methodology and clinical usefulness tonometry is not yet widely applied. The recent introduction of automated airtonometry, replacing the laborious and error-prone manual saline technique, makes tonometry more reliable and easier applicable in the clinical situation. Reliable measurements require inhibition of gastric acid production and measurement in a fasting condition. The lumen-blood PCO2 gradient is the most reliable parameter of gastrointestinal mucosal ischaemia. In the past intraluminal pH--calculated from the intraluminal PCO2 measured by tonometry and the bicarbonate concentration in the blood--has been the parameter most often used. Tonometric parameters are reliable indicators of morbidity and mortality in critically ill patients. The effect of 'tonometry-guided' treatment on the morbidity and mortality is still a matter of debate. Other than using tonometry as a global ('hemodynamic') monitoring device, selective monitoring of the regional perfusion of the digestive tract--such as for diagnostic purpose in suspected chronic ischaemia due to splanchnic arterial disease--is a promising new application area.
Abstract: Diagnosis of gastric ischaemia is difficult and angiography is an invasive procedure. Angiographic findings may not correlate with clinical importance.
Abstract: The tonometric detection of a high intragastric regional P(CO2) (PrCO2) reflecting an elevated intramucosal P(CO2) can be helpful to diagnose mucosal ischemia, if acid secretion is suppressed to avoid intragastric CO2 production through buffering of acid by bicarbonate in the stomach. It is recommended to perform tonometry in the fasting state, but this may hamper feeding of the critically ill. On the other hand, postfeeding tonometry could serve as a diagnostic stress test because feeding increases mucosal blood flow demand, provided that the meal itself does not hamper diffusion of CO2 from mucosa to tonometer balloon and does not generate intragastric CO2, independently from intramucosal P(CO2). We therefore studied the effect of a standard meal on intragastric PrCO2 tonometry in healthy volunteers with suppression of meal-stimulated gastric acid secretion and, presumably, with an adequate mucosal blood flow reserve.
Abstract: Tonometry of PCO2 is a promising method for assessing the oxygen supply to demand ratio of the gastrointestinal mucosa in critically ill patients. A balloon-tipped tonometer is introduced into the stomach or sigmoid colon, and saline is instilled into the balloon. After a time to allow partial equilibration with intraluminal PCO2, saline is aspirated and PCO2 is measured. Intermittent instillation and aspiration of saline allows serial PCO2 measurements, provided correction factors are used to calculate the PCO2 value expected at full equilibration from the PCO2 values measured after short dwell times. The technique is not yet widely applied, partly because of methodological controversies. We evaluated the role of the catheter deadspace as a source of error during PCO2 tonometry. The increase in PCO2 in sigmoid-type tonometers with a normal length (normal tonometer (NT)) and in those with a 50% increase in length and thus deadspace (extended tonometer (ET)), in a saline bath at a PCO2 of 4.8 kPa was assessed. Saline dwell times were 10, 20, 30, 45, 60 and 90 min and the time-dependent PCO2 increase was determined at deadspace PCO2 values of approximately 4.0 and 8.0 kPa following contamination of the catheter deadspace after immersion in saline baths at PCO2 values of 4.8 and 9.6 kPa, respectively, before each measurement cycle. In another experiment, the tonometer was rinsed between measurement cycles to remove deadspace saline containing carbon dioxide and to obviate contamination of instilled saline. PCO2 was measured in a blood-gas analyser, taking into account measurement bias in saline. Failure to remove deadspace saline between measurement cycles resulted in an overestimation of 10% and 6% for the NT and 16% and 10% for the ET, at saline dwell times of 10 and 20 min, respectively, at a deadspace PCO2 of approximately 4.0 kPa. At a deadspace PCO2 of approximately 8.0 kPa, PCO2 was overestimated by 17%, 11% and 5% for the NT and 31%, 20% and 11% for the ET, at dwell times of 10, 20 and 30 min, respectively. Rinsing the NT/ET resulted in accurate assessment of PCO2 at all dwell times, but the dwell time-dependent increase in PCO2 was slightly slower in the ET, particularly at 10 min, after a sink effect of the increased deadspace. Hence, a previously unrecognized deadspace effect caused error during PCO2 tonometry, particularly with short dwell times. This potentially large error can be avoided by rinsing the tonometer before each measurement cycle, allowing accurate PCO2 tonometry even at 10-min saline dwell times, provided that correction factors are used that are specific for catheter size. These findings may help to widen the clinical applicability of tonometry.
Abstract: Factors that affect PCO2 measurement in balloon saline during gastrointestinal tonometry are unclear. They include carbon dioxide diffusion rate, correction factors for calculation of equilibrium PCO2 from measurements at saline dwell times that are shorter than needed for full equilibration, role of blood-gas analyser bias during ex vivo PCO2 measurements in saline, and normal values for intragastric PCO2 (PiCO2) and intramucosal pH (pHi) at equilibrium, and their differences from blood values. In a laboratory study, normal PCO2 changes in a saline-filled tonometer balloon placed in a saline bath at constant PCO2 were described by a non-linear model, with a half-time of mean 4.4 min and 95% equilibration at mean 83 min. In a study in 20 healthy volunteers, PiCO2 build up in a saline-filled tonometer balloon placed in the stomach, measured at dwell times of 10, 20, 30 and 60 min, was slightly (P < 0.05) slower than in vitro, with a half-time of mean 5.8 min and 95% equilibration at mean 110 min. Correction factors to derive equilibrium PiCO2 at short dwell times and independently from blood-gas analyser bias were calculated. The factors differed (P < 0.05) from those currently provided by the manufacturer. Normal threshold values (mean) were: equilibrium PiCO2 < or = 6.6 kPa, pHi > or = 7.33, PiCO2 to blood PCO2 difference < or = 1.1 kPa and pH difference > or = -0.06. PiCO2 did not differ from, and was directly related to, blood PCO2. These values provide a reference base for other studies and show that gastric mucosal PCO2 depends on alveolar ventilation if blood flow is adequate.
Abstract: To study the need for suppression of gastric acid secretion for reliable intragastric partial pressure of carbon dioxide (PCO2) tonometry by evaluating the effect of an oral dose of sodium bicarbonate before and after administration of the H2-blocker ranitidine to mimic CO2 generation following the buffering of acid by bicarbonate in patients after cardiac surgery.
Abstract: Tonometric measurement of an elevated intragastric Pco2 and a decreased calculated gastric intramucosal pH can be used to detect gastric mucosal ischemia, provided that intraluminal production of CO2 through acid buffering by bicarbonate is avoided by adequate acid secretion suppression. If the diffusion rate is known, steady state Pco2 can be calculated when measurement intervals are used that are shorter than needed for complete equilibration. The CO2 diffusion might be influenced by the choice of acid-suppressive drugs, since some of them inhibit gastric carbonic anhydrase (CA) and CA facilitates diffusion of CO2/bicarbonate over the gastrointestinal mucosa. We therefore performed gastric Pco2 tonometry, using acid-suppressive regimens with and without CA inhibition. The diffusion rate of CO2 in a gastric tonometer was studied in healthy volunteers, following intravenously administered ranitidine (group I, N = 8) or ranitidine plus pirenzepine (group II, N = 12), a muscarinic antagonist with CA inhibiting capacities. Measurement intervals were 10, 20, 30 and 60 min. Neither the diffusion rate of CO2 (k = 0.13 +/- 0.02/min in group I and 0.11 +/- 0.02/min in group II), nor the steady-state Pco2 (38 +/- 3 mm Hg in group I and 40 +/- 4 mm Hg in group II), nor the gastric-blood differences in Pco2 and pH differed between groups. These results indicate that diffusion of CO2 into the tonometer balloon is independent of CA and thus of the type of gastric acid secretion inhibition.
Abstract: The choice of solution for gastrointestinal tonometry influences the PCO2 measurement bias, precision and the time required for equilibration. We compared saline with buffered solutions during in vitro tonometry, with respect to systematic and accidental measurement errors and equilibration time.
Abstract: To assess the in vitro performance of a new device, the Tonocap, for semi-continuous air tonometry of regional PCO2 in the gastrointestinal tract.
Abstract: To compare the efficacy of ranitidine bismuth citrate plus clarithromycin (RBC-C) vs. omeprazole plus amoxycillin (OME-AMO) in the cure of Helicobacter pylori infection.
Abstract: The genes for tumour necrosis factor alpha (TNF alpha) and lymphotoxin alpha (LT alpha; TNF beta) are tandemly arranged in the central region of the MHC. They may, therefore, be of importance for the aetiology of MHC-associated diseases. The authors have prospectively studied the secretion of TNF alpha and LT alpha in relation to polymorphisms at positions -308 and -238 in the TNF alpha gene (TNFA), and two polymorphisms in the first intron of the LT alpha gene (LTA), as well as HLA-DR in 30 patients with chronic inflammatory bowel diseases (IBD) and 12 healthy controls. In the Dutch population, the alleles of these four polymorphisms are present in only five combinations, called TNF-haplotypes: TNF-C, -E, -H, -I, and -P. Significant associations between TNF haplotypes and TNF alpha and LT alpha secretion were found when PBMC were cultured with T-cell activators, irrespective of disease. Mean TNF alpha secretion of individuals carrying the HLA-DR3 associated TNF-E haplotype was significantly higher, as compared to individuals without this haplotype (26 441 pg/ml versus 19 629 pg/ml; P = 0.014). Individuals carrying the TNF-C haplotype produced the lowest amount of TNF alpha (17 408 pg/ml; P=0.022). The TNF-C and TNF-E haplotypes differ only at position -308 in the promoter of TNFA. Individuals carrying the HLA-DR1 associated TNF-I haplotype produced significantly less LT alpha when compared to those who lack this haplotype (1979 pg/ml versus 3462 pg/ml; P = 0.006). As the TNF-I haplotype is also associated with low TNF alpha secretion, this haplotype thus defines a 'low secretor phenotype'. In conclusion, this is the first study to show associations between TNF haplotypes and TNF alpha and LT alpha secretion when T-cell stimulators are used. These findings will contribute to define disease heterogeneity in IBD and may be of relevance for understanding the pathogenesis of autoimmune diseases.
Abstract: The majority of patients presenting with acute upper gastrointestinal haemorrhage bleed from peptic diseases erosive gastritis and duodenal or gastric ulcers. Early gastroscopy is essential in order to reach a diagnosis, assess the prognosis, and institute appropriate therapy. In a meta-analysis it was shown that H2-antagonists significantly reduced mortality. However, two large, prospective and placebo-controlled studies with famotidine and omeprazole failed to show reduction of rebleeding or death. The value of endoscopic haemostatic therapy in patients with high-risk peptic ulcers (active bleeding and non-bleeding visible vessel) has been firmly established with 75% decrease in rebleeding and operation rate, and a 40% reduction in mortality. Risk factors for an adverse outcome are: elderly patients, concomitant diseases and large ulcers in the posterior duodenal bulb or on the lesser curvature. The mortality for emergency surgery in upper GI bleeding is still 10-50%. The mortality of elective operations is less than 2%. Some studies have reduced mortality by avoiding emergency surgery through early elective surgery in high-risk patients.
Abstract: The accuracy of computed tomography (CT) and [99mTc]HMPAO granulocyte scintigraphy (GS) for detection of bowel localization, inflammatory activity, and complications in acute inflammatory bowel disease (IBD) was prospectively studied in 32 patients. Of each bowel segment, findings on CT and GS were scored by one blinded observer. Findings on operation or endoscopy served as the gold standard. In Crohn's disease (CD, 17 patients), CT detected bowel pathology (sensitivity 71%, specificity 98%), abscesses (sensitivity and specificity 100%), and fistulas (sensitivity 80%, specificity 100%). In CD, GS had a sensitive of 79% and a specificity of 98% for detection of inflammatory activity. The detection of complications with GS was poor. Segmental inflammatory activity correlated with endoscopy-operative findings for CT (r = 0/86, P < 0.0001) and GS (r = 0.86, P < 0.0001). In ulcerative colitis (UC, 15 patients), GS predicted proximal extension of bowel involvement better than CT. In CD, CT is Superior to GS for localization of both active and fibrostenotic bowel disease, and in detection of the abscesses and fistulas. In UC, GS showed proximal extension more accurately than CT.
Abstract: Seventy-three Helicobacter pylori-positive patients were treated with a combination of clarithromycin and ranitidine in order to eradicate the bacterium. Eradication was successful in 79.5%. In 15 patients eradication failed, and in 11 cases this was due to clarithromycin resistance. In one patient the infecting strain was resistant at the onset of treatment, while in the remaining 10 patients resistance developed during therapy. These isolates had also become resistant to various other antibiotics. Random amplified polymorphic DNA and restriction fragment end-labeling analysis of the isolates showed close genetic relatedness between pre- and post-treatment isolates, indicating that resistance was the result of selection of variants of the infecting strain rather then infection with an exogenous resistant strain. Nucleotide sequence comparisons revealed that all resistant isolates had a single base pair mutation in the 23S rRNA. Since this single point mutation results in co-resistance to various antibiotics at high frequencies, caution should be taken when using clarithromycin as a single antibiotic.
Abstract: Nitric oxide is an important mediator in inflammatory and autoimmune-mediated tissue destruction and may be of pathophysiologic importance in inflammatory bowel disease. We studied whether serum levels of nitrate, the stable end-product of nitric oxide, are increased in active Crohn's disease or ulcerative colitis, in comparison with quiescent disease and healthy controls. The setting was the gastroenterology unit of the Free University Hospital, Amsterdam.
Abstract: Tumor necrosis factor alpha (TNF alpha) and beta (TNF beta) appear to play an important role in the regulation of the inflammatory response. The aim of the present study was to investigate the intrinsic capacity of peripheral blood mononuclear cells (PBMC) to produce these cytokines.
Abstract: A high intragastric PCO2 (iPCO2), determined tonometrically, is the main factor participating in a low gastric intramucosal pH (pHi) and may point to gastric mucosal ischaemia. iPCO2 might also increase, however, after buffering of gastric acid by bicarbonate; the magnitude of this effect and the efficacy of H2 blockers to prevent it are unclear. Ten healthy volunteers (20-24 years) were studied at baseline and after oral ingestion of 500 mg sodium bicarbonate. The same test was carried out one hour after intravenous injection of 100 mg ranitidine. A glass pH electrode for continuous gastric juice pH measurements and a Tonomitor catheter were placed 10 cm distally from the gastro-oesophageal junction. iPCO2 was measured in saline boluses, infused at 30 minute intervals in the balloon at the tip of the Tonomitor. Before ranitidine was given, basal iPCO2 (mean (SD)) was 8.40 (2.53) kPa, and increased to 19.20 (5.87) kPa after sodium bicarbonate (p < 0.001). After ranitidine, the gastric juice pH increased from 1.8 (0.9) to 5.6 (1.3) (p < 0.05), while basal iPCO2 was 5.60 (0.67) kPa (p < 0.01) and did not change after sodium bicarbonate (6.27 (2.67) kPa)). iPCO2 values after acid secretion suppression were similar to those in capillary blood (5.60 (0.40 kPa)). The difference between intragastric and blood PCO2 during normal acid secretion probably results from buffering of gastric acid by gastric bicarbonate, rather than by duodenogastric reflux or saliva entering the stomach. During acid secretion suppression, intragastric equals blood PCO2, even after oral ingestion of sodium bicarbonate. Hence, acid secretion inhibition is mandatory for proper assessment of iPCO2 and pHi as specific measures of the adequacy of gastric mucosal blood flow.
Abstract: The objective of this article is to review splanchnic tonometry. The English literature, involving both animal and human studies, was used for review, with emphasis on papers on physiological and methodological principles and clinical applications. Tonometry involves the measurement of intraluminal PCO2 as a measure of mucosal PCO2 in the gastrointestinal tract via a catheter in, for instance, stomach or sigmoid colon, and the calculation, with help of the blood bicarbonate content and the Henderson-Hasselbalch equation, of the mucosal pH (pHi). The latter is considered as a relatively simple index of the adequacy of mucosal blood flow. Concerning methodology, it is still unclear whether acid secretion should be inhibited for proper assessment of PCO2 in the stomach. Buffering of bicarbonate by gastric acid may elevate the intraluminal PCO2 independently from mucosal PCO2, thereby confounding pHi as a measure of perfusion adequacy. This can be prevented by inhibition of acid secretion. Authors have raised doubts whether the composite variable pHi is of additive value to the acid-base status of arterial blood, so that it is unclear whether a subnormal pHi is a specific and sensitive indicator of mucosal ischemia, as suggested by others on the basis of a decline in the pHi along the gastrointestinal tract in animals subjected to vascular occlusion or circulatory shock. Moreover, tissue PCO2 depends on the PCO2 of supplying blood. Conversely, the bicarbonate concentration in ischemic mucosa may not equal that in arterial blood. Taken together, an elevated tonometer fluid arterial blood PCO2-gradient might be a more sensitive and specific indicator of mucosal ischemia than a decrease in the pHi, analogous to an increase in tissue PCO2 and widening of the venoarterial PCO2 gradient during various types of hypoperfusion, in animals and humans. Although splanchnic ischemia is an early event in shock, the sensitivity and specificity of this index for mucosal ischemia and its clinical value, relative to that of the pHi, have not been formally evaluated yet. Nevertheless, the pHi has been suggested to be of predictive value for gastrointestinal complications, multiple organ failure, success or failure of weaning from mechanical ventilation, and outcome in critically ill patients. Tonometry may be a useful monitoring technique to guide treatment and to improve survival. Splanchnic tonometry is a relatively simple, noninvasive, and thereby promising technique to monitor the critically ill. However, some aspects need further evaluation before the technique can be advocated for routine use.
Abstract: Eighty patients with either bacteriologically confirmed Campylobacter jejuni infection and/or an antibody titre value of at least 1:80, determined by ELISA, were studied. A significant correlation was found between titre value and severity of symptoms (P = 0.015). Although a correlation was noted between symptoms score and endoscopic abnormalities, this was not quite statistically significant (P = 0.053). Comparison of patients with a titre of at least 1:1280 and those with lower titre values revealed a significantly higher symptom score (P = 0.019) and endoscopic score (P = 0.015) in patients with a higher antibody level. By using the previously recommended titre of 1:640 as a cut-off point for active infection, all significant differences were lost. Of 12 patients with positive stool culture, 7 had a titre value of at least 1:1280, suggesting a sensitivity of 58%. However, of 20 patients with negative culture, 4 showed this titre value, three of whom were studied several weeks after the onset of their illness. In those patients with clinically proven Campylobacter infection, the antibody response was characterized by a rapid initial rise and a slow four-fold drop in antibody titre after 3 to 5 months. Colonic involvement of the infection was seen in 63% of our patients with positive cultures. Our results support the conclusion that ELISA is a valuable method of diagnosing C. jejuni infections when stool cultures are likely to become negative, as is the case in prolonged complaints or complications after gastro-enteritis or in proctocolitis or after the use of antibiotics. Serial serum samples have no advantage over a single sample for antibody detection.(ABSTRACT TRUNCATED AT 250 WORDS)
