Biomedical subjects

D Y Graham

Publications and source records attributed to D Y Graham.

At least 451 records · Page 25Linked to original sources

PubMed1989

Campylobacter pylori. The organism and its clinical relevance.

Campylobacter pylori causes type B gastritis and C. pylori infection has been associated with duodenal ulcer, gastric ulcer, non-ulcer dyspepsia, and gastric cancer. Although we have been able to culture C. pylori for only about 5 years, what we now know about this organism can explain many mysteries surrounding peptic ulcer disease. Whenever one investigates a population of ulcer patients for the presence of any accepted potentially important pathogenetic factors, one finds that the population of patients with duodenal ulcer disease differs (statistically) from those without duodenal ulcer disease, but that to a large degree they also overlap. None of the traditional factors can be considered essential and characteristic of chronic duodenal ulcer. The exception is the presence of a C. pylori infection, the presence of which is almost invariable. Several properties of C. pylori have been identified that might be virulence factors, including (a) provoking a marked acute and chronic inflammatory response, (b) rapid motility through gastric mucus, (c) urease activity, (d) a fibrillar adhesin(s), (e) several putative exotoxins, and (f) microinvasion. We can now add to the old dictum "no acid-no ulcer," "no C. pylori-no ulcer" at least as far as chronic duodenal ulcer disease in adults is concerned.

Campylobacter↗

PubMed1989

Sensitivity of the esophageal mucosa to pH in gastroesophageal reflux disease.

To determine the relation between the sensation of pain in gastroesophageal reflux and the pH of the refluxate, we studied 25 individuals with symptomatic gastroesophageal reflux and positive Bernstein tests. We quantitatively assessed the sensitivity of the esophageal mucosa to pain associated with the intraesophageal infusion of eight different HCl solutions (pH 1, 1.5, 2, 2.5, 3, 4, 5, and 6). Test solutions were infused at 8 ml/min through an eight-lumen catheter with the orifices placed 5 cm above the lower esophageal sphincter. Each subject received all eight solutions in a double-blind randomized fashion. The time-to-pain onset increased with increasing pH; i.e., there was a highly significant difference between the time-to-pain and pH (p less than 0.001), with the time-to-pain significantly longer with increasing pH (r = 0.77). In addition to more rapid onset of pain, all subjects experienced pain with the pH 1 and 1.5 solutions, 80% had pain with the pH 2.0 solution, and half had pain with solutions of pH 2.5-6. Fifteen of these subjects underwent 24-h pH monitoring and these tests were examined for factors associated with pain. Only 64% of all pain episodes were associated with a pH drop of less than 4; the lowest pH obtained was not different between episodes with and without pain. Reflux episodes resulting in pain were significantly longer than those without pain and were more often associated with a recently preceding painful episode. Overall, none of the data from the 24-h pH monitoring was useful for predicting pain. The acid infusion studies and the 24-h pH data, taken together, suggest episodes of pain sensitize the patient for subsequent pain.

Adult↗

PubMed1989

In vivo susceptibility of Campylobacter pylori.

Campylobacter pylori infection has been associated with duodenal ulcer, gastric ulcer, and non-ulcer dyspepsia. Although in vitro studies have shown that C. pylori is susceptible to most commonly used antibiotics, predictions from in vitro sensitivity studies have not led to a safe and generally effective therapy; C. pylori has proved to be very difficult to eradicate in vivo. We used the urea breath test to assess the susceptibility of C. pylori in vivo to various drugs. C. pylori was susceptible to bismuth subsalicylate, bismuth subnitrate, and furazolidone. C. pylori was not susceptible (i.e., urease activity remained despite administration of the drug) to the following drugs: 1) antiulcer agents (cimetidine, ranitidine, famotidine, omeprazole, misoprostol, sucralfate, liquid antacids); 2) NSAIDs (aspirin, indomethacin, ibuprofen, naproxen, tolmetin); 3) antibiotics (oral penicillin V, trimethoprim-sulfamethoxazole, dicloxacillin); 4) salts (lithium, ferrous sulfate, gold); 5) miscellaneous (acetaminophen, phenytoin, hydrochlorothiazide, propranolol, metoprolol, metoclopramide, ursodeoxycholic acid). Oral antimicrobials can be administered directly onto the site of infection, so that a very low oral dose will provide many multiples of the in vitro minimal inhibitory concentration. Furazolidone suspension (7 mg) was administered seven times daily (daily dose 49 mg) to three individuals infected by C. pylori during suppression of gastric acid secretion with famotidine (40 mg bid). After 4 days, all subjects had significant reductions in urease activity (two to normal and one to a borderline value). This response suggested that very low-dose therapy may be useful either alone or combined with bismuth. Conclusive establishment of an etiologic (or major contributory) relationship of C. pylori to ulcer disease will require a safe and reliable method to eradicate the organism from the stomach and duodenum.

Anti-Bacterial Agents↗

PubMed1988

Spicy food and the stomach. Evaluation by videoendoscopy.

We used videoendoscopy to investigate the effect of eating spicy foods on the gastric mucosa. We employed four meals: a bland meal of unpeppered steak and french fries (negative control), a bland meal with 1950 mg of aspirin (positive control), a spicy Mexican meal (30 g of jalapeño peppers), and a pepperoni pizza. Twelve subjects (eight men and four women, aged 24 to 43 years) were studied in a randomized, crossover trial with the test meal given at the noon and evening meals; each subject received all four test meals. Each study consisted of a baseline endoscopy, which was repeated approximately 12 hours after the last test meal. Gastric and duodenal damage was scored using a modification of the Lanza scale. Eleven of 12 individuals taking the bland meal plus aspirin developed multiple gastric erosions (median score, C; which equates with "severe" injury). In contrast, the median endoscopic score for the other three meals was 0. Single cases of a single erosion were present after the Mexican meals and after the pizza meals. Another experiment was done to examine the effect of spices directly on the gastric mucosa; approximately 30 g of fresh jalapeño peppers was ground in a food processor and then placed directly into the stomach. Endoscopy after 24 hours revealed no visible mucosal damage. The ingestion of highly spiced meals by normal individuals is not associated with endoscopically demonstrable gastroduodenal mucosal damage.

Adult↗

PubMed1988

Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial.

A double-blind, placebo-controlled study was carried out to see whether the synthetic E prostaglandin, misoprostol, would prevent gastric ulcer induced by non-steroidal anti-inflammatory drugs (NSAIDs). 420 patients with osteoarthritis and NSAID-associated abdominal pain were studied; they were receiving ibuprofen, piroxicam, or naproxen. Endoscopy was done at entry and after 1, 2, and 3 months of continuous treatment with 100 micrograms or 200 micrograms misoprostol or placebo, given four times daily with meals and at bedtime, concurrently with the NSAID. Abdominal pain was rated independently by patients and physicians. A treatment failure was defined as development of a gastric ulcer. Gastric ulcers (0.3 cm in diameter or greater) occurred less frequently (p less than 0.001) in both misoprostol treatment groups (5.6% 100 micrograms and 1.4% 200 micrograms) than in the placebo group (21.7%). The significant difference in ulcer formation between the placebo and the misoprostol treatment groups remained when comparisons were restricted to ulcers greater than 0.5 cm in diameter (12.3% placebo, 4.2% 100 micrograms misoprostol, and 0.7% 200 micrograms misoprostol). Mild to moderate, self-limiting diarrhoea was the most frequently reported adverse effect attributed to misoprostol. These results provide the first clear indication that NSAID-induced ulcers are preventable.

Abdomen↗

PubMed1988

Gastritis. Bringing this enigma into sharper focus.

Type A and type B (probably Campylobacter pylori) gastritis are distinct clinical (but largely asymptomatic) and histologic entities that can be separated from other disease processes. While the association of C pylori gastritis with peptic ulcer disease is well documented, no causal relationship has been established. Acute inflammatory conditions of the stomach secondary to other disease processes, macroscopic abnormalities of the gastric mucosa, and sometimes poorly characterized epigastric pain all carry the name "gastritis." The fact that, as a disease, gastritis remains an enigma largely stems from the multiple implications of the term. An accurate classification system of the gastritides would be helpful but is not yet available. Until it is, the term "gastritis" will have more meaning if accompanied by a description of the type of gastritis or of the responsible etiologic factor, secondary disease, or toxic insult (eg, gastric mucosal injury associated with use of nonsteroidal antiinflammatory drugs). Deletion of the term "gastritis" from the clinical vocabulary and substitution of better terms (eg, "nonulcer dyspepsia," "irritable bowel syndrome") will also serve to clarify the issue.

Campylobacter Infections↗

PubMed1988

Molecular characterization of three rabbit rotavirus strains.

We report biochemical (RNA and protein patterns and gene-coding assignments) and serologic (serotype and subgroup) properties of three strains of rabbit rotaviruses--Ala C11 and R2. The RNA electropherotypes were a standard "short" pattern for R2, an unusual "short" pattern for Ala, and an unusual "long" pattern for C11. Serologic studies indicated that these viruses were all group A serotype 3 rotaviruses. In addition, the Ala and C11 viruses were found to possess subgroup I specificity, whereas the R2 virus possessed subgroup II specificity. In contrast to their distinctive RNA patterns, the polypeptide patterns of the rabbit viruses were similar to those of SA11. To identify cognate genes and determine gene-coding assignments for the rabbit rotaviruses, cDNA probes of individual SA11 genes were hybridized to rabbit rotaviral genomic RNA segments that had been separated by polyacrylamide gel electrophoresis and transferred to filters (Northern blots). The order of genome segments 7-11 for each of the rabbit rotaviruses was unique and differed from that of SA11 genes. These differences were possibly due to rearrangements of the RNA sequences within these individual genome segments. Sequence analysis of the individual RNA segments will confirm whether genome rearrangements are the molecular basis for these novel migration patterns.

Animals↗

PubMed1988

Intragastric accumulation of Evan's blue as a method for assessing aspirin-induced acute gastric mucosal injury in humans.

Aspirin administration results in gastric mucosal damage. Although the pathogenesis of these lesions remains unclear, in animals it appears that increased vascular permeability precedes development of grossly visible lesions. We examined the effect of aspirin administration on gastric vascular permeability in eight healthy subjects. We used gastric accumulation of Evan's blue dye (which is bound to albumin) as a marker of vascular integrity and assessed gastric accumulation of Evan's blue, blood, and DNA during serial 10-min washes. Both bleeding and Evan's blue in the gastric washings increased with time after administration of aspirin in an acid solution (P less than 0.01). Evan's blue increased from a median value of 8 micrograms/10 min to 24.5 micrograms/10 min period after 60 min of aspirin administration. By 20 min after aspirin administration, the accumulation of Evan's blue in the gastric wash was significantly greater than the initial aspirin period (P less than 0.05). Blood loss increased from 147 to 650 micrograms Hgb/10-min period. The increase in bleeding rate did not become significant until 40 min after the first aspirin dose. Our study showed that aspirin-induced gastric mucosal damage can be detected by assessing accumulation of Evan's blue in the gastric contents after aspirin administration. Studies in which various doses of aspirin or other agents are administered will be required to confirm whether the increased vascular permeability actually precedes bleeding in man. Measurement of Evan's blue dye in the gastric contents appears to provide a qualitative (and possibly quantitative) and sensitive early index of gastric mucosal injury.

Adult↗

PubMed1988

Campylobacter pylori and Barrett's esophagus.

Occurrence of C. pylori infection of mucosa outside of the stomach might provide an ideal opportunity to examine C. pylori-mucosal interactions apart from the effects of acid and pepsin. Techniques previously used to examine Barrett's epithelium (for example, special mucin stains or scanning and transmission electron microscopy) might be particularly useful for exploration of new associations and formulation of new hypotheses. Whether C. pylori has a role in development of Barrett's ulcer or adenocarcinoma as a complication of Barrett's esophagus remains unanswered. Most of the current data about C. pylori are primarily observational; further studies are needed for clarification of important microbegut interactions.

Barrett Esophagus↗

PubMed1988

Effect of age on the frequency of active Campylobacter pylori infection diagnosed by the [13C]urea breath test in normal subjects and patients with peptic ulcer disease.

We studied the frequency of active Campylobacter pylori infection in persons from North America (n = 53) or the People's Republic of China (n = 15) who had no gastrointestinal symptoms or a history of ulcer disease and in patients with active or recently active duodenal or gastric ulcers diagnosed by endoscopy (n = 105). C. pylori infection was significantly (P less than .001) more frequent in patients with peptic ulcers (88%) than in the normal group (45%). An age-related increase in the frequency of C. pylori infection in subjects with no gastrointestinal symptoms paralleled the known age-related increase in prevalence of gastritis. The frequency of C. pylori infection in patients with duodenal ulcers was greater than 80%, irrespective of age. C. pylori infection was more common in the Chinese group (age, 20-39 y) than in the North American group of the same age (60% vs. 24%). Association of C. pylori with specific diseases should not be inferred without knowing the prevalence of C. pylori infection in reference populations of the same age and ethnic background.

Adult↗

PubMed1988

Non-replicating oral whole cell vaccine protective against enterotoxigenic Escherichia coli (ETEC) diarrhea: stimulation of anti-CFA (CFA/I) and anti-enterotoxin (anti-LT) intestinal IgA and protection against challenge with ETEC belonging to heterologous serotypes.

An oral killed (non-replicating) whole-cell anti-ETEC vaccine was prepared by treating enterotoxigenic Escherichia coli strain H-10407 (ST + LT +; 078: H11: CFA/I) with a 100%-lethal amount of colicin E2. Colicin E2 is a potent DNA endonuclease which enters the target bacterial cells without disrupting cellular integrity. Thus the vaccine consists of intact cells lacking chromosomal and plasmid DNA but possessing a normal complement of antigens, including CFA/I and enterotoxin(s), unaltered by chemical- or heat-treatment. Young healthy volunteers were administered two oral doses, one month apart, of approximately 3 x 10(10) vaccine cells. Of 22 vaccinees, 17 (77.3%) showed an intestinal anti-CFA/I IgA response and 19 (86.4%) showed an increase in intestinal anti-LT IgA. Twenty of 22 (90.9%) vaccinees had antibody responses to either CFA/I, LT, or both antigens, demonstrating that colicin E2-treated CFA-positive E. coli cells are an efficient vehicle in terms of delivery of antigens to the gut immune system. We previously demonstrated protection of vaccinees against challenge with the living homologous ETEC (strain H-10407). In this study, two groups of 8 vaccinees were challenged with a diarrheagenic dose of virulent ST + LT + ETEC of heterologous serotype; one group was challenged with a CFA/I-positive 063: H- strain and the other group was challenged with a CFA/II-positive 06: H16 strain. Approximately 75% efficacy was achieved in both challenge groups. None of the 16 vaccinees who had responded to both CFA/I and LT became ill upon challenge while both of the vaccinees who had not responded to either antigen did.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1988

Immunoprotective oral whole cell vaccine for enterotoxigenic Escherichia coli diarrhea prepared by in situ destruction of chromosomal and plasmid DNA with colicin E2.

Vaccine regimens which mimic actual infection with bacterial enteropathogens should offer the best opportunity for successful long-term immunoprotection against diarrheal disease caused by enterotoxigenic Escherichia coli (ETEC) or Vibrio cholerae. Based on this principle, we designed and tested an oral whole cell anti-ETEC vaccine consisting of intact cells of ETEC strain H-10407 (ST+LT+; O78:H11:CFA/I) which were rendered incapable of replication by treatment with a potent DNA endonuclease, colicin E2. Young healthy volunteers were administered two oral doses of either placebo or approx. 3 X 10(10) vaccine cells. In a double-blind study, 9 of 10 vaccinees responded with an increase in CFA/I-specific intestinal IgA antibody, determined as percent of total IgA. Challenge with virulent strain H-10407 (5 X 10(9) living cells) produced diarrhea in 8 of 9 (89%) of the placebo-treated volunteers and in 2 of 10 (20%) of the vaccinees. Thus, the colicin E2-killed whole cell vaccine afforded both a significant intestinal immune response and significant protection against challenge with the virulent organism. The data presented here suggest that for this vaccine preparation an intestinal anti-CFA/I IgA response is a good indicator of a protective immune response, which most likely involves antibody responses to a number of antigens in addition to CFA/I. We conclude that the colicin E2 method for preparing an oral anti-ETEC vaccine merits further study and that this method may also be applicable to other enteropathogens.

Administration, Oral↗

PubMed1988

N-acetylneuraminyllactose-binding fibrillar hemagglutinin of Campylobacter pylori: a putative colonization factor antigen.

Campylobacter pylori is the causative agent of gastritis and possibly of peptic and duodenal ulcers in adults. Histological observations show C. pylori attached to gastric epithelium as well as in the mucus layer of the stomach. We found that clinical isolates of C. pylori possess a cell-bound hemagglutinin detectable with human erythrocytes (all phenotypes tested) and those of a variety of animal species. The C. pylori hemagglutinin is antigenic, heat sensitive, and destroyed by pronase and papain but resistant to pepsin and trypsin. The hemagglutinin has fibrillar morphology; C. pylori-erythrocyte interaction displays very intimate contact, which is typical of fibrillae-mediated attachment. Fibrillae were removed from C. pylori by solubilization with N-octylglucose. After partial purification and removal of N-octylglucose by dialysis, the protein reaggregated, with the assembly of fibrillar structures. Hemagglutination inhibition was observed with the sialoproteins fetuin, alpha 2-macroglobulin, and glycophorin A but not with asialofetuin or asialoglycophorin A. The erythrocyte receptor was more sensitive to destruction by a neuraminidase specific for the N-acetylneuraminyl-alpha(2-3)-galactopyranosyl [NeuAc(2-3)Gal] sequence than one specific for NeuAc(2-6)Gal. Hemagglutination-inhibition assays with N-acetylneuraminyl-alpha(2-3)-lactose [NeuAc(2-3)-lactose] and NeuAc(2-6)-lactose confirmed that the C. pylori hemagglutinin preferentially binds to the NeuAc(2-3)Gal isomer of NeuAc-lactose. Based upon the above-described properties of the C. pylori fibrillar hemagglutinin, we conclude that this antigen should be designated as a putative colonization factor antigen.

Antigens, Bacterial↗

PubMed1988

Nucleic acid hybridization studies of mycobactin-dependent mycobacteria.

Using molecular techniques, specifically, DNA-DNA hybridization in solution and measurement of the thermal stabilities of hybrids, we examined the genetic relationships among mycobactin-dependent mycobacteria and between such organisms and other (mycobactin-independent) mycobacteria. The mycobactin-dependent mycobacteria examined included five strains of Mycobacterium paratuberculosis, two wood pigeon isolates, and one bovine isolate that was biochemically identified as Mycobacterium avium. All mycobactin-dependent mycobacteria were found to belong to the same hybridization group and to be closely related to organisms in M. avium complex serovars 2, 8, and 9, but more distantly related to organisms in serovars 7 and 19. Relatively low levels of hybridization were observed with other mycobacterial species examined. Thus, these results provide genetic evidence to support previous biochemical and cultural evidence that indicated that mycobactin-dependent mycobacteria constitute a closely related group of organisms within the M. avium complex.

Animals↗

PubMed1988

Progress in culture and subculture of spheroplasts and fastidious acid-fast bacilli isolated from intestinal tissues.

The efficiency of culture media was compared for the culture and subculture of very slowly growing acid-fast bacilli and spheroplast forms obtained from intestinal tissues of patients with Crohn's disease and ulcerative colitis and from controls without inflammatory bowel disease. Media were developed by modifying a nutrient broth medium based on veal infusion broth and yeast extract. We evaluated the effects of pH and the addition of Tween 80, Dubo oleic albumin complex, an extract from intestinal tissue from a patient with Crohn's disease, horse serum, sucrose, magnesium sulfate, ferrous ammonium sulfate, and sodium citrate. All media contained mycobactin J (2 micrograms/ml). We developed a medium (MG3) which was highly successful in promoting the growth of very fastidious organisms and promoted reversion of spheroplasts to acid-fast rods. MG3 contained veal infusion broth, 1% yeast extract, 10% horse serum, 0.3 M sucrose, 0.2% MgSO4, 0.1% ferrous ammonium sulfate, 0.1% sodium citrate, and 2 mg of mycobactin J per liter. We were able to obtain quantities of organisms sufficient for examination of the organisms by molecular techniques. Successful cultivation of all isolates and reversion of spheroplasts to acid-fast forms encourage further studies of the possibility of a complex association of mycobacteria and Crohn's disease.

Crohn Disease↗

PubMed1988

Mannose-resistant hemagglutination of human erythrocytes by enterotoxigenic Escherichia coli with colonization factor antigen II.

The human erythrocyte receptor which mediates mannose-resistant hemagglutination by enterotoxigenic Escherichia coli possessing colonization factor antigen II is not universally distributed among donors. Mannose-resistant hemagglutination-positive erythrocytes are more common among black donors than nonblack donors; tests with erythrocytes of known antigenic makeup confirm this correlation. Colonization factor antigen II receptor activity of mannose-resistant hemagglutination-positive erythrocytes is unstable when whole blood is stored at 4 degrees C. Also, screening of donors is best performed with enterotoxigenic E. coli possessing colonization factor antigen II composed of the coli surface antigen 1 (CS1) plus CS3, since these consistently produce stronger hemagglutination reactions than strains with colonization factor antigen II composed of either CS2 plus CS3 or CS3 only.

Antigens, Bacterial↗

PubMed1988

Rabbit model of rotavirus infection.

A new small animal model was developed to study parameters of rotavirus infections, including the active immune response. Seronegative New Zealand White rabbits (neonatal to 4 months old) were inoculated orally with cultivatable rabbit rotavirus strains Ala, C11, and R2 and with the heterologous simian strain SA11. The course of infection was evaluated by clinical findings, virus isolation (plaque assay and enzyme-linked immunosorbent assay), and serologic response. All four strains of virus were capable of infecting rabbits as determined by isolation of infectious virus from intestinal contents or fecal samples, by seroconversion, or by a combination of these methods. The responses differed depending on the virus strain used for inoculation. Rabbits remained susceptible to primary infection to at least 16 weeks of age (upper limit examined). Virus excretion in intestinal contents was detected from 6 h to 7 days postinoculation. RNA electropherotypes of inocula and viruses isolated from rabbits were the same in all samples tested. Transmission of Ala virus and R2 virus but not SA11 virus from inoculated animals to uninoculated controls also occurred. In a challenge experiment with Ala virus, 74- and 90-day-old rabbits were rechallenged with Ala 5 weeks after a primary infection with Ala. Virus was excreted in feces from 2 to 8 days after the primary infection but was not excreted after challenge. These results indicate that the rabbit provides an ideal model to investigate both the primary and secondary active immune responses to rotavirus infections and to evaluate candidate vaccines.

Age Factors↗

PubMed1988

Antacid maintenance therapy in the prevention of duodenal ulcer relapse.

The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p less than 0.01) and bedtime Maalox TC (p less than 0.04). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo.

Adult↗