Leaky gut in alcoholic cirrhosis: a possible mechanism for alcohol-induced liver damage

OBJECTIVE: Only 30% of alcoholics develop cirrhosis, suggesting that the development of alcohol-induced liver injury requires one or more additional factors. Animal studies have shown that gut-derived endotoxin is one such factor. Because increased intestinal permeability has been shown to cause endotoxemia, we hypothesized that increased gastrointestinal permeability contributes to the pathogenesis of alcoholic liver disease. This study aimed to measure gastroduodenal and intestinal permeability in alcoholics with and without chronic liver disease and in nonalcoholic subjects with chronic liver disease. METHODS: Gastroduodenal permeability was assessed by measurement of urinary excretion of sucrose after oral administration. Intestinal permeability was assessed by measurement of urinary lactulose and mannitol after oral administration of these sugars. RESULTS: Alcoholics with no liver disease showed a small but significant increase in sucrose excretion. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in urinary sucrose excretion relative to the controls, to the alcoholics with no liver disease, and to the nonalcoholics with liver disease. Alcoholics with chronic liver disease demonstrated a marked and highly significant increase in both lactulose absorption and in the urinary lactulose/mannitol ratio (alcoholics 0.703 vs controls 0.019, p = 0.01). In contrast, alcoholics with no liver disease and nonalcoholics with liver disease showed normal lactulose absorption and normal lactulose/mannitol ratio. CONCLUSION: Because only the alcoholics with chronic liver disease had increased intestinal permeability, we conclude that a "leaky" gut may be a necessary cofactor for the development of chronic liver injury in heavy drinkers.     

Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease

The functional integrity of the small bowel is impaired in coeliac disease. Intestinal permeability, as measured by the sugar absorption test probably reflects this phenomenon. In the sugar absorption test a solution of lactulose and mannitol was given to the fasting patient and the lactulose/mannitol ratio measured in urine collected over a period of five hours. The sugar absorption test was performed in nine patients with coeliac disease with an abnormal jejunum on histological examination, 10 relatives of patients with coeliac disease with aspecific symptoms but no villous atrophy, six patients with aspecific gastrointestinal symptoms but no villous atrophy, and 22 healthy controls to determine whether functional integrity is different in these groups. The lactulose/mannitol ratio (mean (SEM) is significantly higher in both coeliac disease (0.243 (0.034), p < 0.0001)) and relatives of patients with coeliac disease (0.158 (0.040), p < 0.005)) v both healthy controls (0.043 (0.006)) and patients with aspecific gastrointestinal symptoms (0.040 (0.011)). The lactulose/mannitol ratio in relatives of coeliac disease patients was significantly lower than in the coeliac disease patient group (p = 0.04). The lactulose/mannitol ratio was the same in healthy controls and patients with aspecific gastrointestinal symptoms. It is concluded that the sugar absorption test is a sensitive test that distinguishes between patients with coeliac disease and healthy controls. The explanation for the increased permeability in relatives of patients with coeliac disease is uncertain. Increased intestinal permeability may be related to constitutional factors in people susceptible to coeliac disease and may detect latent coeliac disease. The sugar absorption test may therefore be helpful in family studies of coeliac disease.     

Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease

BACKGROUND: Increasing evidence points to a important role for inflammatory cytokines for the pathogenesis of Crohn's disease. AIM: To compare the secretion rate of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by morphologically normal and inflamed intestinal mucosa from patients with Crohn's disease. RESULTS: Organ cultures of intestinal biopsy specimens taken from areas of affected mucosa from patients with Crohn's disease spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared with controls but also biopsy specimens taken in macroscopically and microscopically unaffected areas in the same patients. Concentrations of IL-1 beta and IL-6 measured in the supernatant fluid of biopsy cultures were positively correlated with the degree of tissue involvement measured by both endoscopic and histological grading. By contrast, TNF-alpha concentrations were not correlated to endoscopic and histological grading. CONCLUSIONS: These consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing mucosa from patients with Crohn's disease provide evidence for a sustained immune stimulation in Crohn's disease even in the absence of patent inflammation. The results shed a new light on the role of inflammatory cytokines in the onset of intestinal tissue damage in Crohn's disease and suggest that the range of intestinal lesions in Crohn's disease may be wider than suspected on the basis of regular endoscopic and histological examinations.     

Forefront of lung cancer therapy

The differential urinary excretion of orally administered lactulose and mannitol is used to evaluate intestinal permeability. This test usually involves a 5- to 6-hr urine collection. We hypothesized that a shorter collection time would give an equivalent result. Forty-three patients with a variety of gastrointestinal symptoms and diagnoses (group 1) and 42 patients with Crohn's disease (group 2) had a standard lactulose/mannitol permeability test. The lactulose and mannitol urinary excretion was calculated using the first urine (group 1) or the 1-hr and 2-hr urine (group 2) and was compared to the values calculated from the routine 5- or 6-hr collection. Lactulose excretion kinetics, expressed as the percent of the total urinary excretion within a given time period, were as follows: 21% in first hour (group 2), 29% in second hour (group 2), and 46% in first 2.5 hr (group 1). Mannitol urinary excretion kinetics were 16%, 31%, and 44%, respectively. The lactulose/mannitol ratio based on a standard urine collection correlated well with the ratio based on just the first urine produced by the patient (R2 = 0.94; P < 0.001; group 1) and the 2-hr urine (R2 = 0.464; P < 0.001; group 2). Future use of the lactulose/mannitol ratio to assess intestinal permeability may be able to be simplified by shortening the urine collection time.     

Upper digestive tract dyspepsia and early gastric cancer

AIM: The study of the frequency and evolution of upper digestive tract dyspepsia in a group of patients operated for early gastric cancer (EGC) and to perform a strategy of diagnosis for the patients with long term upper digestive tract dyspepsia. METHODS: Clinical data of 35 patients operated for EGC were retrospectively evaluated. The frequency, characteristics and evolution time of upper digestive tract dyspepsia, main when it began more than 6 months before surgery, were analyzed. Radiologic and endoscopic exams carried out for diagnosis were also evaluated. Histological diagnosis of surgical specimens were considered, looking for the presence of chronic atrophic gastritis, intestinal metaplasia, and peptic gastric ulcer. RESULTS: Long-term upper digestive tract dyspepsia was present in 27 patients (mean evolution time of 43.4 months). Clinical changes of previous symptoms that suggested gastric carcinoma were not found in 15 patients. Concurrent peptic gastric carcinoma were not found in 15 patients. Concurrent peptic gastric ulcer along with EGC was diagnosed by histology in 11 patients, and chronic atrophic gastritis and intestinal metaplasia were both present in the non-tumoral gastric mucosa in all cases. CONCLUSIONS: 1) Unspecific upper digestive tract dyspepsia is frequently found in patients with EGC. 2) Endoscopy should be the first exam performed in patients with upper digestive tract dyspepsia. 3) The patients with gastric ulcer, chronic atrophic gastritis or intestinal metaplasia must be submitted to sequential endoscopic follow-up.     

Luminal bacteria and small-intestinal permeability

BACKGROUND: The influence of luminal bacteria on small-intestinal permeability has not been fully assessed. This study addressed this issue. METHODS: Thirty-four subjects (mean age 64 years; range 22-95 years) were investigated for possible small-intestinal bacterial overgrowth (SIBO) with culture of a small-intestinal aspirate. A lactulose/mannitol small-intestinal permeability test was performed, small-intestinal histology assessed and serum vitamin B12 concentrations measured in all subjects. Permeability was also assessed in a control group of 34 asymptomatic volunteers. RESULTS: Urinary lactulose/mannitol ratios were significantly increased in subjects with SIBO with colonic-type flora (P < 0.0005), even in the absence of villous atrophy. Urinary lactulose/mannitol ratios were increased in this group due to significantly increased urinary lactulose concentrations (P < 0.0005) rather than reduced urinary mannitol levels, after correcting for inter-subject variations in renal function. Counts of intraepithelial lymphocytes of CD8 phenotype were significantly increased in this group (P = 0.003). Although a significant correlation was found between intraepithelial lymphocyte counts and small-intestinal permeability overall (P < 0.002), these counts were not significantly different in subjects with SIBO with colonic-type flora whose permeability values were < or = > 0.028, the upper limit of normal in asymptomatic controls. Serum vitamin B12 concentrations did not differ significantly between groups (P > 0.5). Ageing did not independently influence small-intestinal permeability (P > 0.5). CONCLUSIONS: Small-intestinal permeability is increased in subjects with SIBO with colonic-type bacteria. This effect is independent of ageing and not mediated by vitamin B12 deficiency. Although counts of intraepithelial lymphocytes of CD8 phenotype are increased in this disorder, it is also unlikely that these cells play an important causative role in this process. Routine light microscopic assessment underestimates the prevalence of small-intestinal functional disturbance in this disorder.     

Ectopic gastric mucosa in the upper esophagus: detection and radiographic findings

PURPOSE: To detect and characterize the appearance of islands of ectopic gastric mucosa in the upper esophagus at routine examination of the upper gastrointestinal (GI) tract. MATERIALS AND METHODS: Well-distended upper esophagus was documented with spot radiographs obtained with routine double-contrast examination performed after administration of high-density barium in nine patients. Detected lesions were confirmed by means of endoscopy and biopsy. RESULTS: Twelve lesions were detected. Radiographic findings were characterized by either a discrete, shallow depression surrounded by a subtle, rimlike elevation on double-contrast images or by a pair of small indentations on the same wall on full-column, single-contrast images at the level of the thoracic inlet. Endoscopic examination revealed well-circumscribed areas of reddish mucosa located 15-26 cm from the incisors. CONCLUSION: Ectopic gastric mucosa in the upper esophagus is easily demonstrated at routine examination of the upper GI tract. Diagnosis can be based on location and characteristic radiographic appearance.     

Small intestine in lymphocytic and collagenous colitis: mucosal morphology, permeability, and secretory immunity to gliadin

There is a recognised association between the "microscopic" forms of colitis and coeliac disease. There are a variety of subtle small intestinal changes in patients with "latent" gluten sensitivity, namely high intraepithelial lymphocyte (IEL) counts, abnormal mucosal permeability, and high levels of secretory IgA and IgM antibody to gliadin. These changes have hitherto not been investigated in microscopic colitis. Nine patients (four collagenous, five lymphocytic colitis) with normal villous architecture were studied. Small intestinal biopsies were obtained by Crosby capsule; small intestinal fluid was aspirated via the capsule. IEL counts were expressed per 100 epithelial cells, and intestinal IgA and IgM antigliadin antibody levels were measured by ELISA. Small intestinal permeability was measured by the lactulose:mannitol differential sugar permeability test. IEL counts were normal in all cases, median 17, range 7-30. Intestinal antigliadin antibodies were measured in six cases and were significantly elevated in two patients (both IgA and IgM). Intestinal permeability was measured in eight cases and was abnormal in two and borderline in one. These abnormalities did not overlap: four of nine patients had evidence of abnormal small intestinal function. Subclinical small intestinal disease is common in the two main forms of microscopic colitis.     

The sugar permeability test reflects disease activity in children and adolescents with inflammatory bowel disease

OBJECTIVES: To investigate the relationship of intestinal permeability in children and adolescents with inflammatory bowel disease (IBD) to disease activity, disease extent, and response to therapy. Study design: Patients with new and established diagnoses of IBD (12 Crohn's disease [CD] and 18 ulcerative colitis [UC]) were studied. Intestinal permeability was evaluated by measuring with high-performance liquid chromatography 5-hour urinary excretion ratio of lactulose/L-rhamnose (L/Rh). RESULTS: In 8 of 9 patients with active CD, the L/Rh ratio was higher than the reference range (0.006 to 0.074, n = 36). In inactive CD (n = 3) the L/Rh ratio was within the reference range. In 6 of 7 patients with active extensive UC, the L/Rh ratio was elevated. In inactive extensive UC (n = 6) the normal permeability ratio was shown. In both active CD and active extensive UC, the frequency of elevated intestinal permeability was significantly greater than values in both inactive forms. The permeability ratio was normal in 4 of 5 patients with active left-sided colitis. In 5 of 7 patients (3 CD, 4 UC), repeat permeability values entered the reference range after acute phase therapy. Two patients with persistently elevated intestinal permeability (1 CD, 1 UC) had a disease flare-up within 6 months. CONCLUSIONS: Intestinal permeability is a marker of disease activity in CD and extensive UC. Serial permeability test may be useful in monitoring disease activity.     

Mucosal injury and disruption of intestinal barrier function in HIV-infected individuals with and without diarrhea and cryptosporidiosis in northeast Brazil

The effects of AIDS-related diarrhea--with and without cryptosporidiosis and microsporidiosis--on intestinal function and injury were studied in 40 AIDS patients and 13 healthy volunteers from Fortaleza, Brazil. The differential urinary excretion of ingested lactulose and mannitol was used as a marker of barrier disruption and overall villous surface area. HIV-infected patients with diarrhea had a 2.8-fold higher lactulose to mannitol excretion ratio than HIV-positive patients without diarrhea and a 10.4-fold higher ratio than healthy volunteers. Moreover, those with crypotosporidial infection had a lactulose to mannitol ratio almost 6-fold greater than those without diarrhea and nearly 3-fold higher than those with non-cryptosporidial diarrhea. This effect involved both decreased mannitol excretion (decreased intestinal absorptive area) and increased lactulose excretion (mucosal barrier disruption). The single patient with microsporidial infection had a nearly 3-fold higher ratio than healthy volunteers. Alpha1-antitrypsin tests were positive in two of five (40%) HIV-positive patients with cryptosporidial infections compared with none of 12 HIV-infected patients with non-cryptosporidial diarrhea. These findings confirm that HIV infection is associated with profound intestinal dysfunction and injury, even in those without diarrhea. Disruption of the intestinal barrier is even greater, however, in HIV-infected patients with cryptosporidial diarrhea, with potential nutritional consequences.     

Science, technology and health literacy for the 21st century. A future for dentistry. Percy T. Phillips Memorial Lecture

Group II phospholipase A2 has been proposed to play an important role in the pathophysiology of inflammatory bowel diseases. This enzyme has also been linked to host defence mechanisms against bacteria. The current study aimed at measuring the mass concentrations of group II phospholipase A2 in serum and colonic mucosa of patients with Crohn's disease of different severity and of appropriate control patients without any inflammatory disease. The activity of the disease was determined by clinical factors (the simple index score) and endoscopic and histological scoring. The mass concentration of group II phospholipase A2 was measured by a time-resolved fluoroimmunoassay. The mass concentrations of group II phospholipase A2 in serum and colonic mucosa were significantly higher both in patients with active and inactive Crohn's disease when compared with controls. There was statistically significant difference in the mass concentration of group II phospholipase A2 in colonic mucosa but not in serum between inactive and active Crohn's disease. The current results indicate that the mass concentration of group II phospholipase A2 is increased in serum and colonic mucosa of patients with Crohn's disease and that the latter is associated with the degree of the inflammatory activity in the intestinal wall. These results support the idea that group II phospholipase A2 is involved in the local and generalised pathological processes of Crohn's disease.     

Effect of L-glutamine and n-butyrate on the restitution of rat colonic mucosa after acid induced injury

BACKGROUND: L-glutamine and n-butyrate are important nutrients for colonocytes affecting both their structure and function. The effect of these epithelial substrates on resealing of rat distal colon after acid induced injury was studied. METHODS: Isolated colonic mucosa of 32 rats was mounted in Ussing chambers and exposed to Krebs-Ringer solution for four hours. Epithelial injury was induced by short-term exposure to luminal hydrochloric acid and resealing was studied with or without added glutamine or butyrate. RESULTS: Glutamine (luminal and serosal) reduced tissue conductance, mannitol and lactulose permeability, and permeation of enteropathogenic Escherichia coli. Glutamine (serosal) diminished conductance and mannitol permeability. Both interventions stimulated bromodeoxyuridine incorporation in nuclei of colonocytes. Luminal butyrate had no measurable effect on these parameters. CONCLUSIONS: These data suggest that L-glutamine stimulates repair mechanisms of rat colonic mucosa after acid injury. This effect on the gut barrier is associated with a stimulation of crypt cell proliferation. The addition of glutamine to parenteral solutions may be beneficial for patients under intensive care whose intestinal barrier is weakened in the course of sepsis and trauma.     

Oral contraceptive use and myocardial infarction

Inflammatory bowel disease (IBD) denotes chronic inflammatory disorders of gastrointestinal tract of unknown etiology that comprises 2 major groups: ulcerative colitis (UC) and Crohn's disease (CD). Disregulation of the intestinal immune system both at humoral and cellular level constitutes an important element in the multifactorial pathogenesis of IBD. The expression of pro-inflammatory cytokines, most notably IL-1, IL-6, TNF-alpha and chemokines (IL-8, ENA-78, MCP-1, RANTES) in intestinal mucosa from IBD patients is markedly enhanced, however, it is not always accompanied by increases in cytokines' serum levels. In IBD also significant changes occur in the tissue expression of immunoregulatory cytokines: increased levels of IL-2 mRNA and IFN-gamma mRNA, and decreased expression of IL-4 were found in affected intestinal mucosa. Chronic intestinal lesions of patients with Crohn's disease are associated with a Th1 type cytokine profile. The clinical effectiveness of anti-TNF-alpha antibodies and of IL-10 has been demonstrated in steroid-refractory Crohn's disease patients. The data demonstrating the role of cytokines in the pathogenesis of IBD should be carefully analyzed because of limitations imposed by the patient- and sample-related parameters. Further investigations will clarify the significance of the impairments in cytokine network for the initiation and progression of the IBD.     

Serum and intestinal fluid immunoglobulins and jejunal IgA secretion in Crohn's disease

Immunoglobulins in serum and proximal intestinal fluids and secretion of IgA by cultured jejunal mucosa were measured in 12 healthy subjects and 36 patients with Crohn's disease. Concentrations of IgA, IgG, IgM, and IgE in serum and intestinal fluids were similar in the two groups, except for increased serum IgA concentrations in the patients. Elevation of IgA and chronicity of disease were correlated, which suggests that the IgA alteration was a response to duration of disease rather than a primary pathogenetic factor. IgA secretion by cultured jejunum was similar in control and patient groups. Thus, no evidence was found that abnormalities of secretory immunoglobulins are pathogenetically involved in Crohn's disease.     

False-positive gliadin and endomysium antibodies and exocrine pancreatic insufficiency as pitfalls in the differential diagnosis of duodenal Crohn's versus celiac disease

We report a 13-yr-old boy with Crohn's disease in the upper gastrointestinal tract presenting with abdominal pain, failure to thrive, recurrent fever, iron-deficient anemia, and exocrine pancreatic insufficiency. Initially, latent celiac disease was suggested because of normal endoscopic findings, the finding of non-specific inflammation on histological evaluation of duodenal biopsies, positive IgA and IgG gliadin, as well as endomysium antibodies and exocrine pancreatic insufficiency. There was no response to a gluten-free diet. A reevaluation revealed Crohn's disease.     

Inverse relationship between fenfluramine-induced prolactin release and blood pressure in humans

OBJECTIVES: Up to 20% of patients with AIDS have abnormal intestinal permeability (IP). Glutamine seems to play an important role in preventing the increase in IP and loss of intestinal mucosal mass associated with total parenteral nutrition, and may be superior to glucose for oral rehydration in the setting of intestinal infection. This study was designed to see if supplemental glutamine could alter the abnormal IP of AIDS. METHODS: Randomly chosen patients with AIDS from the Jacobi Medical Center human immunodeficiency virus (HIV) clinic underwent IP testing using lactulose and mannitol. Those with abnormal IP were enrolled. Duodenal biopsies were performed with a Crosby capsule and the patients were randomized in a double-blind fashion to receive placebo or glutamine (4 g/day or 8 g/day) for 28 days, after which intestinal permeability tests and duodenal biopsies were repeated. Intestinal morphology was graded by ratio of villus height to crypt depth, and by degree of inflammation. RESULTS: All patients complied with the therapy and there were no dropouts or reported side effects. The results showed less worsening of IP with the 4 g/day dose, compared with placebo. At the 8 g/day dose, there was stabilization of IP and improved absorption of mannitol. Intestinal morphology and inflammation did not change in any group. CONCLUSIONS: These results, although not significant, suggest a trend towards improved IP and enhanced intestinal absorption with glutamine. Glutamine doses of at least 20 g/day may be necessary to improve IP. We recommend further studies at higher doses and for longer durations.     

The epidemiology of hemorrhage from the upper gastrointestinal tract in the mid-nineties--has anything changed?

BACKGROUND/AIMS: Gastrointestinal hemorrhage is a frequent medical problem and a significant cause of morbidity and mortality. The aim of this retrospective analysis, which was carried out at our institution, was to establish the causes of hemorrhage from the upper digestive tract during a 3-year period. METHODOLOGY: The retrospective study includes those patients in which urgent endoscopic investigations of the upper digestive tract were carried out between 1 January 1994 and 31 December 1996. RESULTS: 2150 patients were investigated: 797 women and 1353 men. The average age of our patients was 57 years (a 3-97 year span, SD+/-17). In 665 patients (35.8%), endoscopic investigation of the upper digestive tube revealed signs of acute hemorrhage or traces of previous hemorrhage. Endoscopic hemostasis was carried out in 577 cases (31.1%). Sequelae of ulcer disease were the cause of hemorrhage in 46.1% of investigated patients. Frequent causes of hemorrhage were also inflammatory, hemorrhagically-erosive changes of the gastric and duodenal mucosa (21.9%), ruptured esophageal varices (9.4%), and esophageal reflux disease (8.0%). In 13.6% of patients the cause of hemorrhage did not lie in the upper digestive tract. In 50.3% of cases the gastrointestinal hemorrhage manifested itself by the discharge of melenic feces, and in 33.1% by hematemesis. 47.2% of our patients were aged over 60. CONCLUSIONS: Also in our society sequelae of ulcer disease are the most significant cause of gastrointestinal hemorrhage. Hemorrhages are frequent in elderly patients who usually have accompanying diseases.     

Number, fixation properties, dye-binding and protease expression of duodenal mast cells: comparisons between healthy subjects and patients with gastritis or Crohn's disease

There is an accumulation of evidence to suggest that mast cells may play a key role in gastrointestinal inflammation. We have investigated the numbers and heterogeneity in staining properties of mast cells in biopsies of the duodenum of normal subjects (n = 10), and of normal duodenum from patients with Crohn's disease of the ileum and/or colon (n = 7) or with Helicobacter-associated gastritis of the antrum/corpus (n = 6). In normal donors, two subsets of mast cells, one located in the duodenal mucosa and the other in the submucosa, were clearly distinguished by their morphology and dye-binding properties. Whereas submucosal mast cells stained metachromatically with Toluidine Blue after neutral formalin fixation and emitted a yellow fluorescence after staining with Berberine sulphate, those in the mucosa were invisible using these stains. In patients with gastritis or Crohn's disease, there were marked changes in the numbers of mucosal mast cells compared with control subjects even though the duodenal biopsies were from apparently uninvolved tissue. Gastritis was associated with increased mucosal mast cell numbers (controls: 187 +/- 23 cells mm-2; gastritis: 413 +/- 139 cells mm-2; p = 0.0004), but mean mucosal mast cell counts in the uninvolved duodenum of Crohn's patients were actually decreased (34 +/- 30 cells mm-2, p = 0.0147). The clear differentiation between mucosal and submucosal mast cells on the basis of metachromasia with Toluidine Blue was not seen in biopsies from the patients with gastritis or Crohn's disease. Previous studies which have suggested that there are no distinct mucosal and submucosal mast cell subsets in the human intestine may, therefore, have been affected by the use of tissue from diseased subjects. Heterogeneity in the expression of mast cell tryptase and chymase was seen by immunohistochemistry using specific antibodies, but the relative numbers of mast cell subsets were critically dependent on the methods used. Using a sensitive staining procedure, the majority of mucosal mast cells stained positively for chymase as well as for tryptase, an observation confirmed by immunoelectron microscopy and immunoabsorption studies. Our findings suggest that early stages in intestinal inflammation may be reflected in changes in mast cell numbers and in their staining properties, and call for a reappraisal of mast cell heterogeneity in the human intestinal tract.     

Transient increase in chloride cell number and heat shock protein expression (hsp70) in brown trout (Salmo trutta fario) exposed to sudden temperature elevation

OBJECTIVE: To determine whether acepromazine (ACE) and butorphanol (BUT) combination can be used for restraint of dogs during positive-contrast upper gastrointestinal tract (UGIT) examination. ANIMALS: 6 healthy dogs. PROCEDURE: In a randomized crossover design study, weekly UGIT examinations were performed on each dog for 5 weeks after administration of normal saline solution (0.5 ml), xylazine (1.0 mg/kg of body weight), or a combination of ACE (0.1 mg/kg) and 1 of 3 doses of BUT (0.05, 0.2, 1.0 mg/kg). Gastrointestinal tract emptying time, GI motility, pulse, respiratory rate, and quality of restraint were assessed. RESULTS: Total gastric emptying time was significantly prolonged by use of an ACE and BUT (0.05 mg/kg) combination. Xylazine and higher dosages of BUT significantly prolonged gastric and intestinal emptying times. All anesthetic protocols significantly decreased motility and facilitated nonmanual restraint. Xylazine and BUT (1.0 mg/kg) significantly decreased pulse and respiratory rate. CONCLUSION: The ACE and BUT combination prolonged GI tract emptying times, decreased GI motility, and facilitated nonmanual restraint for duration of the examination. Although GI motility was decreased and total gastric emptying time was prolonged, administration of ACE (0.1 mg/kg) plus BUT (0.05 mg/kg) allowed morphologic examination of the GI tract within 5 hours. Xylazine prolonged GI tract emptying, decreased GI motility, and provided good to excellent initial restraint. Clinical Relevance-The ACE and BUT combination prohibits functional examination of the GI tract; however, morphologic examination is possible when low dosages of BUT (0.05 mg/kg) are used.     

Evaluation of Triage screening for drugs of abuse in postmortem blood and urine samples

BACKGROUND: Impaired changes in gastric epithelium proliferation have been described in Helicobacter pylori infection, and a progressive increase of proliferating cells has been shown with the progression of mucosal lesions. AIMS: Purpose of this investigation was to study the effect of eradication on bacterium-induced proliferative changes, evaluated by the proliferating cell nuclear antigen labelling index (PCNA LI) and its relationship to the ras oncoprotein p21, involved in early events of gastric carcinogenesis. PATIENTS AND METHODS: This retrospective study was performed, before and after therapy, in five different groups of patients with progressive stages of Helicobacter pylori damage (N: normality; HG: histological gastritis with normal endoscopy; EHG: histological gastritis with endoscopic chronic erosions; CIM: complete intestinal metaplasia; IIM: incomplete intestinal metaplasia). RESULTS: Six months after eradication, a normalization of PCNA LI was observed in the areas of gastritis, but not in those of intestinal metaplasia, which showed on unchanged type. Moreover, immunohistochemical membrane expression of ras oncoprotein p21 was only associated to intestinal metaplasia. The protein was also expressed in the cytoplasm in 3 patients with incomplete type. CONCLUSIONS: These results suggest that the development of intestinal metaplasia may be associated with an alteration in the control of gastric epithelium proliferation and could represent an initial stage in gastric carcinogenesis. Nevertheless, further genetic changes are necessary for a complete progression to neoplastic disease. A long-term follow-up on extension, type, proliferative situation and oncoprotein expression in areas of intestinal metaplasia may be helpful to explain whether the present data provide new information on the mechanism of Helicobacter pylori induced gastric carcinogenesis.