Acute Stress Ulceration Research Articles

THE EFFECT OF PLACENTAL CRYOEXTRACT ON THE STATE OF PROTEIN-LIPID METABOLISM IN THE GASTRIC MUCOSA IN EXPERIMENTAL STRESS-INDUCED ULCERS

Introduction. Peptic ulcer is one of the most prevalent diseases of the gastrointestinal tract. Stress factor is considered to have the highest impact on the development of ulcers, as it is present in almost all cases of onset and exacerbation of this disease. Acute stress ulcers occur with severe injuries, acute diseases of various organs, shock, a sharp drop in blood pressure, oxygen deficiency of body tissues, liver, kidney and others. Given the above facts, in the correction of stress-induced lesions of the gastric mucosa (GM) therapeutically, the target should consider not only reducing the aggression factors of gastric juice, but also the normalization of changes in protein and carbohydrate metabolism in GM. In this aspect, our attention was drawn to the domestic biotechnological preparation of placental cryoextract (CEP), which has a range of valuable biological effects. The aim is to study the effect of cryopreserved placenta extract on the state of protein-lipid metabolism in the gastric mucosa in a model of water-immobilization stress in rats. Materials and methods of research. The studies were performed on 28 nonlinear laboratory male rats weighing 200–220 g. Stress-induced gastric ulcer was modeled under water-immobilization stress (WIS) in rats according to the method of Takagi et al. To obtain the homogenate, the GM was perfused with cold (+ 4°C) buffer solution and homogenized at 3000 rpm (teflon/glass). The content of oxidatively modificated proteins (OMP) in GM was determined by Dubinina spectrophotometric method. The content of total lipids in the GM was determined spectrophotometrically by color reaction with sulfophosphovaniline reagent. Phospholipids (PL) were fractionated by the method of Svetashev and Vaskovsky. Research results. Evaluation of changes in protein metabolism in GM showed that the level of total protein in rats, which were preventively administered CEP before WIS, was almost comparable with that of intact rats, i.e., 50.1 ± 1.7 μg/mg tissue and 51.1 ± 1.3 μg/mg of tissue, respectively, which indicated the elimination of disorders of protein homeostasis with the introduction of the studied cryoextract. Studies of changes in total lipids and PL showed that the content of PL of animals treated with CEP was 26.9 ± 0.9%, which was not significantly different from that of intact animals (30.5 ± 0.9%) and, at the same time, it was by 7.3% higher (p < 0.001) as compared with animals who were administered esomeprazole. Conclusions. Prophylactic five-day administration of CEP to WIS leads to normalization of all evaluated indices, in particular, to increase of the total protein level by 29.0% (p <0.01), decrease of oxidatively modified proteins level by 20.6% (p <0.01), and the 2.3-fold increase (p <0.001) of the level of phospholipids in the total lipids pool.

Peptic Ulcer Diseases

Peptic ulcers are defects or breaks in the inner lining of the gastrointestinal (GI) tract. Although the pathogenesis is multifactorial they tend to arise when there is an imbalance between protective and aggressive factors, such as when GI mucosal defense mechanisms are impaired in the presence of gastric acid and pepsin. Peptic ulcers extend through the mucosa and the muscularis mucosae, a thin layer of smooth muscle separating the mucosa from the deeper submucosa, muscularis propria, and serosa. Peptic ulcer disease affects up to 10% of men and 4% of women in Western countries at some time in their lives. This chapter discusses the pathogenesis of peptic ulcer disease and the etiologic contribution of Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, and gastrinoma or other hypersecretory states. Also addressed are rare and unusual causes for ulcers and GI bleeding. A section on the diagnosis of peptic ulcers discusses clinical manifestations, physical examination findings, laboratory and imaging studies, and surgical diagnosis. Differential diagnosis is also reviewed. Tests to establish the etiology of peptic ulcer disease include endoscopy, quantitative serologic tests, the urea breath test, and the fecal antigen test. Discussed separately are treatments for uncomplicated duodenal ulcers, uncomplicated gastric ulcers, intractable duodenal or gastric ulcers, complicated peptic ulcers (bleeding ulcers, acute stress ulcers, perforated ulcers, obstructing ulcers, fistulizing ulcers, and Cameron ulcers), H. pylori ulcers, and gastric cancer. Figures illustrate the etiopathogenesis of peptic ulcers, prevalence of H. pylori infection in duodenal and gastric ulcer patients compared with normal controls, the approach to a patient with new and undiagnosed ulcerlike symptoms refractory to antisecretory therapy, an upper GI series showing an uncomplicated duodenal ulcer, a chest x-ray showing pneumoperitoneum from a perforated duodenal ulcer, gastric biopsy samples showing H. pylori organisms, and the approach to treatment and follow-up in patients with either complicated or uncomplicated duodenal or gastric ulcer. Tables list differential diagnoses of peptic ulcer disease, commonly used regimens to eradicate H. pylori, additional antimicrobial agents with activity against H. pylori, and FDA-approved antisecretory drugs for active peptic ulcer disease. This chapter contains 5 figures, 6 tables and 78 references.

Peptic Ulcer Diseases

Peptic ulcers are defects or breaks in the inner lining of the gastrointestinal (GI) tract. Although the pathogenesis is multifactorial they tend to arise when there is an imbalance between protective and aggressive factors, such as when GI mucosal defense mechanisms are impaired in the presence of gastric acid and pepsin. Peptic ulcers extend through the mucosa and the muscularis mucosae, a thin layer of smooth muscle separating the mucosa from the deeper submucosa, muscularis propria, and serosa. Peptic ulcer disease affects up to 10% of men and 4% of women in Western countries at some time in their lives. This chapter discusses the pathogenesis of peptic ulcer disease and the etiologic contribution of Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, and gastrinoma or other hypersecretory states. Also addressed are rare and unusual causes for ulcers and GI bleeding. A section on the diagnosis of peptic ulcers discusses clinical manifestations, physical examination findings, laboratory and imaging studies, and surgical diagnosis. Differential diagnosis is also reviewed. Tests to establish the etiology of peptic ulcer disease include endoscopy, quantitative serologic tests, the urea breath test, and the fecal antigen test. Discussed separately are treatments for uncomplicated duodenal ulcers, uncomplicated gastric ulcers, intractable duodenal or gastric ulcers, complicated peptic ulcers (bleeding ulcers, acute stress ulcers, perforated ulcers, obstructing ulcers, fistulizing ulcers, and Cameron ulcers), H. pylori ulcers, and gastric cancer. Figures illustrate the etiopathogenesis of peptic ulcers, prevalence of H. pylori infection in duodenal and gastric ulcer patients compared with normal controls, the approach to a patient with new and undiagnosed ulcerlike symptoms refractory to antisecretory therapy, an upper GI series showing an uncomplicated duodenal ulcer, a chest x-ray showing pneumoperitoneum from a perforated duodenal ulcer, gastric biopsy samples showing H. pylori organisms, and the approach to treatment and follow-up in patients with either complicated or uncomplicated duodenal or gastric ulcer. Tables list differential diagnoses of peptic ulcer disease, commonly used regimens to eradicate H. pylori, additional antimicrobial agents with activity against H. pylori, and FDA-approved antisecretory drugs for active peptic ulcer disease. This chapter contains 76 references.

Clinical efficacy of primary closure in laparoscopic common bile duct exploration (A report of 2 429 cases)

Objective To investigate the clinical efficacy of primary closure in laparoscopic common bile duct exploration (LCBDE). Methods The retrospective cross-sectional study was conducted. The clinicopathological data of 2 429 patients who underwent primary closure in LCBDE in the Second Hospital of Chengdu City from March 1992 to December 2017 were collected. Patients underwent laparoscopic cholecystectomy (LC) + stone extraction using LCBDE or extracorporeal shock wave lithotripsy (ESWL), laparoscopic endoscopic sphincteropapillotomy (LEST) was performed selectively, then underwent laparoscopic endoscopic nasobiliary drainage (LENBD) or laparoscopic transabdominal antegrade-guide common bile duct stent implantation, finally underwent primary closure of common bile duct. Observation indicators: (1) surgical situations; (2) postoperative recovery; (3) postoperative short-term complications; (4) follow-up situation. Follow-up using outpatient examination and telephone interview was performed to observe long-term surgical complications once every 3 months up to 1 year postoperatively. Measurement data with normal distribution were represented as ±s. Measurement data with skewed distribution were described as M (range). Results (1) Surgical situations: of 2 429 patients, 2 251 underwent successful stone extraction using LCBDE, relief of the obstruction and primary closure of common bile duct, with depletion of stones; 15 underwent stone extraction using conversion to open surgery, with depletion of stones; 163 had residual stones or surgery-related complications. Of 2 429 patients, 1 144, 898, 223, 110 and 54 were respectively detected in grade N or 0, 1, 2, 3 and 4 of laparoscopic distal of the common bile duct smooth classification (LDSC); 599 underwent LEST, 367 underwent LENBD, 207 indwelled urinary catheter through cystic duct stump, 125 underwent laparoscopic transabdominal antegrade-guide common bile duct stent implantation and 1 131 underwent primary closure in LCBDE only. Number of removing the stones, diameter of common bile duct, volume of intraoperative blood loss and operation time was (2.5±0.2)per case, (0.7±0.4)cm, (22.4±2.6)mL and (100±12)minutes, respectively. (2) Postoperative recovery: time of postoperative gastrointestinal function recovery, duration of hospital stay and treatment expenses were respectively (2.5±0.5)days, (7.3±1.2)days and (2.7±0.3)×104 yuan. Of 2 429 patients, 367 removed nasobiliary catheter at 3-7 days postoperatively, 207 removed urinary catheter at 3-6 weeks postoperatively, and 125 removed common bile duct stent through duodenoscope port at 1-4 months postoperatively. (3) Postoperative short-term complications: incidence of postoperative short-term complications in 2 429 patients was 6.711%(163/2 429). ① Ninety-four patients with bile leakage were cured after drainage and symptomatic and supportive treatment. ② Of 29 patients with residual stones: 25 with residual stones of common bile duct were cured by stone extraction using endoscopic sphincterotomy of duodenal papilla, and 4 with residual stones of intrahepatic bile duct didn′t receive treatment. ③ One patient died at 15 days after surgery for pancreatic cancer. ④ Of 39 with postoperative other complications: 2 with postoperative hemorrhage were cured by laparoscopic reoperation; 12, 19 and 3 were respectively complicated with postoperative inflammatory stenosis of duodenal papilla induced to short-term obstructive jaundice, mild acute pancreatitis and stress ulcer bleeding of upper digestive tract, and they were improved by endoscopy or non-operation treatment; 2 with stenosis of bile duct didn′t receive treatment; 1 had a miss ligation at bending section of front zone of nasobiliary catheter, and ligation was removed by endoscopic retrograde cannulation of the pancreatic at 19 days postoperatively. (4) Follow-up situation: of 2 429 patients, 1 749 were followed up for 3-12 months, with a median time of 6 months. During the follow-up, of 1 749 patients, 2 had mild stenosis in the primary closure area of common bile duct incision and 1 had stenosis of duodenal papilla, they were not treated, and other patients didn′t have related complications. Conclusion Controlling strictly the operative indication, primary closure of common bile duct in LCBDE is safe and feasible, with satisfactory clinical outcomes. Key words: Hepatolithiasis; Cholelithiasis; Obstruction of biliary tract; Common bile duct exploration; Primary closure; Laparoscopy

Prophylactic proton pump inhibitors in femoral neck fracture patients - A life - and cost-saving intervention.

Introduction Acute gastrointestinal stress ulceration is a common and serious complication of trauma. Prophylactic proton pump inhibitors (PPIs) or histamine receptor antagonists have been used in poly-trauma, burns and head and spinal injuries, as well as on intensive care units, for the prevention of acute gastric stress ulcers. Methods We prospectively studied the use of prophylactic PPIs in with femoral neck fracture patients, gathering data on all acute gastric ulcer complications, including coffee-ground vomiting, malena and haematemesis. We then implemented a treatment protocol in which all patients were given prophylactic PPIs, again prospectively collecting all data. Results Five hundred and fifteen patients were included. Prior to prophylactic PPI, 15% of patients developed gastric stress ulcer complications, with 3% requiring acute intervention with oesophagogastroduodenoscopy (OGD), 5% requiring transfusions and 4% experiencing surgical delays. All patients had delayed discharges. Following PPI implementation, no patients developed gastric stress ulcer complications. Conclusions Femoral neck fracture patients create a substantial workload for orthopaedic units. The increasingly elderly population often have comorbidities, and concomitantly use medications with gastrointestinal side effects. This, combined with the stress of a fracture and preoperative starvation periods increases the risk of gastric ulcers. Here, the use of prophylactic PPIs statistically reduced the incidence of gastric stress ulcers in patients with femoral neck fractures, resulting in fewer surgical delays, reduced length of hospital stay and reduced stress ulcer-related mortality.

Anti-inflammatory, Gastroprotective, and Cytotoxic Effects ofSideritis scardicaExtracts

Sideritis scardica Griseb. (ironwort, mountain tea), an endemic plant of the Balkan Peninsula, has been used in traditional medicine in the treatment of gastrointestinal complaints, inflammation, and rheumatic disorders. This study aimed to evaluate its gastroprotective and anti-inflammatory activities. Besides, continuously increasing interest in assessing the role of the plant active constituents preventing the risk of cancer was a reason to make a detailed examination of the investigated ethanol, diethyl ether, ethyl acetate, and N-butanol extracts regarding cytotoxicity. Oral administration of the investigated extracts caused a dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. Gastroprotective activity of the extracts was investigated using an ethanol-induced acute stress ulcer in rats. The cytotoxic activity of plant extracts was assessed on PBMC, B16, and HL-60 cells and compared to the cytotoxicity of phenolic compounds identified in extracts. Apoptotic and necrotic cell death were analyzed by double staining with fluoresceinisothiocyanate (FITC)-conjugated annexin V and PI. The developed HPLC method enabled qualitative fingerprint analysis of phenolic compounds in the investigated extracts. Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4 mg/kg), which produced a 50 % decrease in inflammation, diethyl ether and N-butanol extracts exhibited about the same effect in doses of 200 and 100 mg/kg (53.6 and 48.7 %; 48.4 and 49.9 %, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine. The diethyl ether extract showed significant dose-dependent cytotoxicity on B16 cells and HL-60 cells, decreasing cell growth to 51.3 % and 77.5 % of control, respectively, when used at 100 µg/mL. It seems that phenolic compounds (apigenin, luteolin, and their corresponding glycosides) are responsible for the diethyl ether extract cytotoxic effect. It also appears that induction of oxidative stress might be involved in its cytotoxicity, since B16 and HL-60 cells increased their ROS production in response to treatment with diethyl ether extract. Neither of the tested extracts nor any phenolic compounds showed significant cytotoxic effect to human PBMC. These results demonstrated the potent anti-inflammatory and gastroprotective activities, as well as the promising cytotoxicity.

Pantoprazole for the Treatment of Peptic Ulcer Bleeding and Prevention of Rebleeding

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers.

Anti-inflammatory, Gastroprotective, Free-Radical-Scavenging, and Antimicrobial Activities of Hawthorn Berries Ethanol Extract

Hawthorn [Crataegus monogyna Jacq. and Crataegus oxyacantha L.; sin. Crataegus laevigata (Poiret) DC., Rosaceae] leaves, flowers, and berries are used in traditional medicine in the treatment of chronic heart failure, high blood pressure, arrhythmia, and various digestive ailments, as well as geriatric and antiarteriosclerosis remedies. According to European Pharmacopoeia 6.0, hawthorn berries consist of the dried false fruits of these two species or their mixture. The present study was carried out to test free-radical-scavenging, anti-inflammatory, gastroprotective, and antimicrobial activities of hawthorn berries ethanol extract. Phenolic compounds represented 3.54%, expressed as gallic acid equivalents. Determination of total flavonoid aglycones content yielded 0.18%. The percentage of hyperoside, as the main flavonol component, was 0.14%. With respect to procyanidins content, the obtained value was 0.44%. DPPH radical-scavenging capacity of the extract was concentration-dependent, with EC50 value of 52.04 microg/mL (calculation based on the total phenolic compounds content in the extract). Oral administration of investigated extract caused dose-dependent anti-inflammatory effect in a model of carrageenan-induced rat paw edema. The obtained anti-inflammatory effect was 20.8, 23.0, and 36.3% for the extract doses of 50, 100, and 200 mg/kg, respectively. In comparison to indomethacin, given in a dose producing 50% reduction of rat paw edema, the extract given in the highest tested dose (200 mg/kg) showed 72.4% of its activity. Gastroprotective activity of the extract was investigated using an ethanol-induced acute stress ulcer in rats with ranitidine as a reference drug. Hawthorn extract produced dose-dependent gastroprotective activity (3.8 +/- 2.1, 1.9 +/- 1.7, and 0.7 +/- 0.5 for doses of 50, 100, and 200 mg/kg, respectively), with the efficacy comparable to that of the reference drug. Antimicrobial testing of the extract revealed its moderate bactericidal activity, especially against gram-positive bacteria Micrococcus flavus, Bacillus subtilis, and Lysteria monocytogenes, with no effect on Candida albicans. All active components identified in the extract might be responsible for activities observed.

Acute stress ulceration prophylaxis: point prevalence surveys in intensive care units in Victoria, 1997 and 2005

Acute stress ulceration prophylaxis: point prevalence surveys in intensive care units in Victoria, 1997 and 2005

Helicobacter pylori infection is not associated with an increased hemorrhagic risk in patients in the intensive care unit

IntroductionThe potential role of Helicobacter pylori in acute stress ulcer in patients in an intensive care unit (ICU) is controversial. The aim of this study was to determine the frequency of H. pylori infection in ICU patients by antigen detection on rectal swabs, and to analyze the potential relationship between the presence of H. pylori and the risk of digestive gastrointestinal bleeding.MethodsIn this prospective, multicenter, epidemiological study, the inclusion criteria were as follows: patients admitted to the 12 participating ICU for at least two days, who were free of hemorrhagic shock and did not receive more than four units of red blood cells during the day before or the first 48 hours after admission to the ICU. Rectal swabs were obtained within the first 24 hours of admission to the ICU and were tested for H. pylori antigens with the ImmunoCard STAT! HpSA kit. The following events were analyzed according to H. pylori status: gastrointestinal bleeding, unexplained decline in hematocrit, and the number of red cell transfusions.ResultsThe study involved 1,776 patients. Forty-nine patients (2.8%) had clinical evidence of upper digestive bleeding. Esophagogastroduodenoscopy was performed in 7.6% of patients. Five hundred patients (28.2%) required blood transfusion. H. pylori antigen was detected in 6.3% of patients (95% confidence interval 5.2 to 7.5). H. pylori antigen positivity was associated with female sex (p < 0.05) and with a higher Simplified Acute Physiology Score II (SAPS II; p < 0.05). H. pylori antigen status was not associated with the use of fiber-optic gastroscopy, the need for red cell transfusions, or the number of red cell units infused.ConclusionThis large study reported a small percentage of H. pylori infection detected with rectal swab sampling in ICU patients and showed that the patients infected with H. pylori had no additional risk of gastrointestinal bleeding. Thus H. pylori does not seem to have a major role in the pathogenesis of acute stress ulcer in ICU patients.

The Role of Proton Pump Inhibitors in Acute Stress Ulcer Prophylaxis in Mechanically Ventilated Patients

This article reviews the use of proton pump inhibitors, other pharmacological therapies, and nonpharmacological therapies for the prevention of acute stress ulcers in critically ill patients.

The Role of Proton Pump Inhibitors in Acute Stress Ulcer Prophylaxis in Mechanically Ventilated Patients

The Role of Proton Pump Inhibitors in Acute Stress Ulcer Prophylaxis in Mechanically Ventilated Patients

Helicobacter pylori in intensive care: why we should be interested.

Helicobacter pylori is estimated to infect over 50% of the world's population, the majority of whom are asymptomatic. Although most research to date has focused on local gastroduodenal disease manifestations, the potential impact of H. pylori infection and the associated chronic active inflammation on systemic disease processes is now being explored. This review addresses three aspects of emerging importance regarding H. pylori in intensive care medicine: acute gastric stress ulceration, nosocomial infection, and the potential modulatory effect on the systemic stress response. The role of H. pylori in acute stress ulceration remains uncertain, but it is unlikely to have the same major aetiological role as in peptic ulcer disease. The pathogenesis of both acute stress ulceration and H. pylori gastritis suggest overlapping mechanisms of gastric mucosal damage and H. pylori may augment stress ulceration incidence and severity. Nosocomial infection of both staff and patients with H. pylori has been suggested by serological studies, and increased H. pylori infection has been reported in intensive care staff. This has significant short- and long-term health implications and also raises questions regarding the efficacy and implementation of routine infection control precautions in intensive care. Finally, H. pylori infection has been linked with the pathogenesis of many extra-intestinal diseases, but the evidence is weak and the relationship between H. pylori and systemic diseases remains controversial. However, the potential for H. pylori to modulate systemic disease processes, particularly the systemic stress response in critical illness, is both theoretically plausible and therapeutically tantalising and requires further investigation.

In vivo characterization of the molecular-genetic changes in gastric mucosa during the development of acute gastritis and stress ulceration.

Trauma patients are at risk for the development of stress ulceration. Stress ulceration should be associated with increased heat-shock gene (iHSP70) and an inhibition of the trefoil peptide, spasmolytic polypeptide (SP), and mucin (MUC5AC) gene expressions. Male Sprague-Dawley rats (10 weeks old) were restrained for 0-, 4-, 8-, 12-, and 24-hour periods of time. Gastric ulcers were graded using a one- to three-point scoring system. The level of mucosal gene expression was determined at each time point for three genes: iHSP70, SP, and MUC5AC. Gastric ulceration developed in direct proportion to the duration of restraint. Gastric ulceration was preceded by increased iHSP70 and decreased SP and MUC5AC gene expressions. Restraint-induced gastric ulceration was preceded by an up-regulation of iHSP70 and a down-regulation of SP and MUC5AC gene expressions.

Helicobacter pylori infection in intensive care: increased prevalence and a new nosocomial infection.

The pathogenesis of acute gastric stress ulceration in the seriously ill is uncertain, and any role of Helicobacter pylori infection is unknown. We aimed to assess the relationship between H. pylori serological status and stress ulceration in seriously ill patients, as well as H. pylori serological status in intensive care nurses as a marker for nosocomial infection. Prospective epidemiologic survey. Adult intensive care unit in a university teaching hospital. One hundred patients, 100 nurses, and 500 blood donors as community controls. H. pylori serological status was measured in patients, staff, and controls using a rapid whole blood test. Upper gastrointestinal bleeding and risk factors for acute stress ulceration were recorded. In seriously ill patients, H. pylori seropositivity (67%) was significantly higher than in the control group (39%) (p < .001). In patients, seropositivity was not related to age, country of birth, diagnostic category, severity of illness, or risk score for stress ulceration. There was a trend toward increased macroscopic gastric bleeding in seropositive patients. In intensive care nurses, H. pylori seropositivity (40%) was significantly higher than in age-matched controls (19%) (p < .001). Only duration of intensive care nursing was significantly associated with seropositivity (p = .02). The unexpectedly high H. pylori seropositivity rate in this seriously ill cohort raises the possibility that under intensive care conditions, H. pylori infection may modulate responses to illness and injury, with consequent clinical implications. Furthermore, the elevated seropositivity rate in intensive care nurses suggests that H. pylori can be nosocomially transmitted.

Stress Ulceration and Gastric Mucosal Cell Kinetics: The Influence of Prophylaxis against Acute Stress Ulceration

Acute gastric stress ulceration occurs frequently in severely ill patients. Mucosal ischemia is central to the etiology of stress ulceration. The ability of the mucosa to restore continuity when damaged is one of the most important of the local defence mechanisms against injury. The aims of this study were to investigate this restitutive process during stress ulcer formation and to determine the effect of prophylaxis against stress ulceration on gastric mucosal cell kinetics. Nuclear DNA was radiolabeled in vivo with tritiated thymidine, and after autoradiography the position and number of labeled cells along the gastric mucosal gland were determined. Wistar rats were studied immediately and 48 hr after cold restraint stress. The labeling index in the proliferative zone of the gastric mucosa was significantly suppressed immediately after stress (12.58% vs 16.81% for unstressed controls, P < 0.001). This effect persisted for 48 hr after stress (9.89% vs 16.35% for unstressed controls, P < 0.001). Prophylaxis against stress ulceration with cimetidine or allopurinol prevented this suppression of gastric mucosal cell kinetics and promoted early migration of labeled cells towards the surface of the mucosal gland. Allopurinol prophylaxis was associated with migration of mucosal cells immediately following stress greater than that following cimetidine prophylaxis (14.0% vs 9.3% surface layer labeling index, P < 0.01). Allopurinol, a xanthine oxidase inhibitor, reduces oxygen free radical production during ischemia reperfusion injury. These results emphasise the importance of the gastric mucosal defence mechanisms in protection against injury and indicate the role of ischemia in the aetiology of acute gastric stress ulceration.

Stress and Personality in Patients with Chronic Peptic Ulcer

The concept that stress and personality are associated with ulcer is widely held by lay persons and to some extent by the medical community. By means of epidemiological techniques and more precise terminology, the role of psychosomatic factors in ulcer disease has been more clearly defined. Regarding acute stress, the number of events experienced and the change and distress they are purported to produce has been found to be similar in ulcer patients and their controls matched on age, sex, and social class. However, chronic difficulties, i.e., events or circumstances that have persisted for > or = 6 months, are twice as common in duodenal ulcer patients as in controls. Events, either acute or chronic, are more strongly associated with duodenal ulcer if they contain a component involving personal threat or goal frustration. Associations that have been found between acute or chronic stress and duodenal ulcer have been relatively weak, with odds ratios of 2 to 3. For some patients, it is possible that depression and social incongruity may have played some role in initiating ulcer disease. Personality studies have shown that ulcer patients are more neurotic than controls, but the difference is small and there is no evidence to indicate an ulcer personality. As regards both stress and personality, gastric ulcer patients do not differ from duodenal ulcer patients.

A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate- or ranitidine-treated intensive care unit patients

To compare the frequency of acute stress ulceration and secondary pneumonia caused by aerobic Gram-negative bacilli in ICU patients treated with either sucralfate or ranitidine. Prospective, randomized study. ICU, university hospital. Sixty adult patients who were mechanically ventilated and at risk of developing stress ulceration. The patients were randomized to receive either sucralfate (1 g every 6 hrs) via the nasogastric tube or iv ranitidine (50 mg every 6 hrs). If the gastric pH was less than 3.5 in the latter group, 30 mL of 0.3M sodium citrate was given via the nasogastric tube. On admission, the frequency rate of erosion/ulceration (assessed with the endoscope) was 13.5%. After 4 days, this rate had increased to 18% in sucralfate-treated patients and 36% in ranitidine-treated patients (NS). Mean gastric pH was more alkaline in the ranitidine-treated patients (5.50) compared with the sucralfate-treated patients (4.26) (p less than .01). This pH permitted a higher occurrence rate of gastric colonization by aerobic Gram-negative bacilli in ranitidine-treated patients (64.3%) compared with sucralfate-treated patients (23.8%) (p less than .01). Retrograde bacterial colonization from the stomach to oropharynx and trachea occurred more frequently in ranitidine-treated patients compared with sucralfate-treated patients. Ultimately, the occurrence rate of pneumonia was greater in the ranitidine-treated (35.7%) than in the sucralfate-treated patients (10.3%) (p less than .05). Based on our findings, we recommend the adoption of sucralfate for routine prophylaxis against stress ulceration.

Histamine2-Receptor Antagonists

THIS article reviews the clinical pharmacology of histamine2-receptor antagonist drugs (H2 blockers) and their usefulness in the treatment and prevention of acid-peptic disorders — namely, peptic ulcer disease, Zollinger—Ellison syndrome, gastroesophageal reflux disease, and acute stress ulcers and erosions. Erosive gastritis and erosive duodenitis are often considered acid-peptic diseases, but because they overlap with peptic ulcer disease they are not considered as separate entities in this review. Non-ulcer dyspepsia is not included as an acid-peptic disorder since it does not appear to respond to therapy with H2 blockers or antacids.1 H2 blockers are quite effective . . .

Gastric mucosal acid‐base balance

Acute gastric ulceration induced by haemorrhagic shock is associated with profound intramucosal acidification due to diffusion of luminal H+ into the mucosa. High-HCO3- metabolic alkalosis protects the mucosa against this ulceration, whereas low-HCO3- respiratory alkalosis does not, suggesting that lack of systemic and intramucosal HCO3-, rather than tissue acidosis per se, renders the mucosa susceptible to ulceration. In normal mucosa, disruption of the mucosal barrier by taurocholate, ethanol or acetylsalicylic acid leads to efflux of alkali (HCO3-) from the mucosa, with generation of an alkaline buffer layer at the epithelial surface to protect the mucosa from further damage. In ischaemic mucosa no such protective alkaline layer is formed, and exposure to luminal acid leads to severe acidification of and damage to the mucosa. The efflux of alkali may be driven by capillary hydrostatic pressure, since no such protective alkaline efflux occurs in vitro, but rather exposure to luminal acid and barrier-breaking agents results in intracellular acidification. The potential pathogenetic role of a disrupted intramucosal acid-base balance, as well as the protective effect of systemic and intramucosal HCO3- in acute gastric stress ulceration is further substantiated by the in vitro findings that perfusion conditions simulating in vivo ulcerogenic conditions provoke intracellular acidosis, and serosal HCO3- significantly contributes to the maintenance of normal intracellular pH in surface epithelial cells exposed to luminal acid.