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D Y Graham

Publications and source records attributed to D Y Graham.

At least 325 records · Page 18Linked to original sources
PubMed1994

Helicobacter pylori: the new bug on the (paraffin) block.

A nameless spirillar organism in search of a disease only a few years ago, Helicobacter pylori has seen its fortunes suddenly reversed. After a rapid succession of name changes and some acrimonious disputes across continents, in less than a decade H. pylori has been catapulted to the centre stage of gastroenterological and microbiological research and has topped the most-wanted list of the pharmaceutical industry. The discovery of H. pylori has provided the momentum for the formation of the group that eventually created the Sydney System. Today, H. pylori is increasingly recognized as one of the most prevalent human pathogens worldwide. Its causal association with chronic active gastritis is undisputed and its role in the pathogenesis of peptide ulcer disease, although still poorly understood, is universally accepted. Furthermore, possible connections between chronic H. pylori infection and gastric carcinoma and primary gastric lymphoma are now being explored with increasing alacrity. With a few notable exceptions, pathologists have remained passive spectators of these exciting discoveries and have allowed gastroenterologists and microbiologists to set the pace in the quest for the determinants of gastritis, peptic ulcer and gastric cancer. This article is intended to outline some of the accepted facts on the development, progression, and pathology of H. pylori gastritis and to pose questions about this elusive infection. The authors hope that it might also contribute to stimulate further research, particularly on those aspects that are eminently suited to be addressed by pathologists.

Gastric Mucosa↗
PubMed1994

Identification and characterization of Mycobacterium paratuberculosis recombinant proteins expressed in E. coli.

Mycobacterium paratuberculosis is the causative agent of Johne's disease, a chronic enteritis in ruminants, and it has also been isolated and identified from patients with Crohn's disease, an inflammatory bowel disease. The control of Johne's disease has been hampered by the lack of a reliable diagnostic test because of the large degree of antigenic cross-reactivity between mycobacterial and non-mycobacterial species. To help identify specific antigen(s) or epitope(s), an M. paratuberculosis expression library was screened with antibodies and DNA probes. In total, 54 clones were randomly picked, purified, and characterized by DNA probes and monoclonal antibodies with known specificity to individual mycobacterial antigens. Four clones carrying the heat shock protein 65K-, two representing the secreted protein 32K-, three representing the 21K-, and 20 clones representing the specific insertion element of M. paratuberculosis (IS900)-encoding genes and their gene products were identified and characterized. Well-defined recombinant antigens and/or epitopes representing M. paratuberculosis may facilitate the development of specific diagnostic tests and the investigation of their role in these chronic diseases.

Antibodies, Monoclonal↗
PubMed1994

Helicobacter pylori-induced microvascular protein leakage in rats: role of neutrophils, mast cells, and platelets.

BACKGROUND/AIMS: Previous studies indicate that a water extract of Helicobacter pylori (HPE) can promote neutrophil-endothelial cell interactions in vivo and in vitro. The objectives of this study were to assess whether HPE alters the rate of albumin leakage in rat mesenteric venules and identify the factors that mediate the HPE-induced microvascular dysfunction. METHODS: Intravital microscopy was used to continuously monitor leukocyte adherence and emigration and albumin leakage in rat mesenteric venules during superfusion with HPE. RESULTS: HPE increased leukocyte adherence and emigration and microvascular albumin leakage. The enhanced albumin leak could be subdivided into two components: an early (within 10 minutes) and a later (within 30 minutes) phase. HPE also elicited perivenular mast cell degranulation and the formation of platelet-leukocyte aggregates within post-capillary venules. The HPE-induced early phase of albumin leakage was attenuated by pretreatment with a mast cell stabilizer. The HPE-induced late phase of albumin leakage was reduced by monoclonal antibodies directed against either CD11b/CD18 or intercellular adhesion molecule 1. A monoclonal antibody against P-selectin also inhibited the HPE-induced platelet-leukocyte aggregation and reduced the later phase of albumin leak. CONCLUSIONS: HPE-induced microvascular dysfunction appears to be a consequence of interstitial and intravascular cell-cell interactions.

Albumins↗
PubMed1994

The gastric cardia in Helicobacter pylori infection.

Helicobacter pylori gastritis is believed to be both more prevalent and more severe in the antrum than in the corpus. The mucosa of the cardia is architecturally similar to that of the antrum. This study was designed to test the hypothesis that intensity of H pylori infection and the associated inflammation are similar in the cardia and the antrum and are greater in these locations than in the corpus. A total of 445 gastric biopsy specimens were obtained from predetermined sites from 50 subjects (42 with demonstrated H pylori infection). Slides were stained with a combined stain to simultaneously visualize H pylori, mucosal morphology, and inflammatory infiltrate. Numbers of H pylori, inflammatory responses, and intestinal metaplasia were graded on a scale from 0 to 5. Helicobacter pylori was detected in the cardia of 40 of the 42 infected subjects (95%). Helicobacter pylori density was similar in the three gastric regions. The intensity of chronic active gastritis was similar in the antrum and the cardia, and was higher in these locations than in the corpus (P < .005). Lymphoid follicles were significantly less prevalent in the cardia and in the corpus than in the antrum (P < .05). Helicobacter pylori infection was as prevalent in the cardia as in the rest of the stomach and its density was similar in all sites of antrum, corpus, and cardia. The inflammatory responses characteristic of chronic active gastritis, except for lymphoid follicles, were similar in the antrum and the cardia and in both these locations were more intense than in the corpus. The significance of these findings is discussed with respect to the relationship between H pylori infection and the genesis of gastric adenocarcinoma and lymphoma.

Adult↗
PubMed1994

Simultaneous visualization of Helicobacter pylori and gastric morphology: a new stain.

Although the histopathologic patterns associated with Helicobacter pylori infection have been described, details of the interaction between bacteria, epithelial cells, and inflammatory cells remain elusive. One of the limiting factors has been the lack of a staining technique that allows the simultaneous visualization of H pylori and tissue morphology. By combining three commonly available stains (Steiner, hematoxylin-eosin, and alcian blue at pH 2.5) into a single procedure we have developed a stain that permits the optimal detection of H pylori in tissue sections while simultaneously allowing the histopathologic evaluation of all salient characteristics of the gastric mucosa. This procedure is inexpensive, as easy to perform as any silver stain, and provides consistent results. This stain is as sensitive as the Warthin-Starry stain for the detection of H pylori and significantly more sensitive than hematoxylin-eosin alone (> 99% v 85% when compared with the hematoxylin-eosin stain in a series of 332 positive biopsy specimens; > 99% v 61% in 49 biopsy specimens with rare bacteria). This stain is particularly useful for the visualization of small numbers of bacteria, such as in the evaluation of posttreatment gastric biopsy specimens, in specimens with abundant mucus or debris, and in specimens from the corpus, where H pylori usually does not elicit strong inflammatory responses and, therefore, pathologists' index of suspicion tends to be low.

Biopsy↗
PubMed1994

Norwalk virus infection of volunteers: new insights based on improved assays.

Norwalk virus infection is a common cause of gastroenteritis in humans. The clinical features and virologic and immunologic responses following oral administration of Norwalk virus to 50 volunteers were monitored. New ELISAs using recombinant virus particles as the antigen source were used to assess the pattern of virus shedding and the specific immune responses. Forty-one subjects (82%) became infected; 68% were symptomatic and 32% were asymptomatic. The proportion of subjects infected was similar for those with and without preexisting antibody (82% vs. 60%; P > .2). The magnitude of seroconversion was highest in subjects who had vomiting. The peak of viral shedding was between 25 and 72 h, and virus first appeared in stool at 15 h. Specimens collected 7 days after inoculation remained positive. These results show a higher infection rate, more subclinical infections, and longer virus excretion following Norwalk virus inoculation than previously recognized.

Adult↗
PubMed1994

Short report: omeprazole-tetracycline combinations are inadequate as therapy for Helicobacter pylori infection.

BACKGROUND: Current triple antimicrobial therapies cure Helicobacter pylori infection in 60-90% of cases but are cumbersome. Addition of omeprazole to amoxycillin has been shown to enhance effectiveness when compared to amoxycillin alone. METHOD: We studied omeprazole 20 mg t.d.s. plus tetracycline 500 mg q.d.s. for 14 days (OMP/TCN) and omeprazole 40 mg in the morning plus tetracycline 500 mg q.d.s. along with bismuth subsalicylate tablets 2 q.d.s. (OMP/TCN/BSS) for 14 days. Forty-four patients (19 OMP/TCN, 25 OMP/TCN/BSS) with H. pylori peptic ulcer disease were studied. H. pylori status was evaluated at least 4 weeks after ending antimicrobial therapy. RESULTS: In the OMP/TCN group cure of H. pylori infection was achieved in 5/19 (26%). Adding bismuth to the regimen improved the results; 4 weeks after ending therapy cure of H. pylori infection was achieved in 12/25 (48%). CONCLUSIONS: Neither regimen can be recommended for routine cure of H. pylori infection. Although one cannot predict which antimicrobial therapies will be enhanced by the addition of omeprazole, these data suggest that future studies should evaluate drugs whose effectiveness is compromised by low pH.

Adult↗
PubMed1994

Clarithromycin-amoxycillin therapy for Helicobacter pylori infection.

BACKGROUND: More convenient therapies are needed to treat Helicobacter pylori infection successfully. Clarithromycin and amoxycillin are effective against H. pylori both in vivo and in vitro. Recent success with a high dose amoxycillin-metronidazole combination therapy led us to evaluate clarithromycin-amoxycillin dual therapy for H. pylori infection. METHODS: We tested the combination of clarithromycin 500 mg t.d.s. with meals plus amoxycillin 750 mg t.d.s. with meals for 10 days for its effect on H. pylori infection in 29 patients with documented H. pylori peptic ulcers. There were 27 men and 2 women, ranging in age from 23 to 77 years. H. pylori and ulcer status were evaluated at entry and at least 4 weeks after ending antimicrobial therapy. For ulcer healing, ranitidine 300 mg was given each evening for 6 weeks. H. pylori status was determined by CLOtest and histology. RESULTS: H. pylori infection was cured in 86% (95% CI = 78-99%). Compliance averaged 93% by pill count. Ten patients (34%) experienced mild side effects: eight reported dysgeusia and two had mild diarrhoea; none discontinued therapy because of side effects. CONCLUSION: We conclude that dual therapy with clarithromycin and amoxycillin is a safe and effective alternative regimen for the successful treatment of H. pylori infections.

Administration, Oral↗
PubMed1994

Comparative assessment of phenolphthalein and phenolphthalein glucuronide: is phenolphthalein glucuronide a better laxative?

BACKGROUND: Phenolphthalein is widely used as a safe and effective laxative. After oral administration, phenolphthalein is absorbed in the small bowel and is conjugated in the liver to phenolphthalein glucuronide which passes into the colon where it is deconjugated and the active compound, phenolphthalein, is released. Since phenolphthalein glucuronide does not undergo enterohepatic circulation it should theoretically have a more rapid onset of action and a lower threshold dose for laxation. The present study was designed to examine this issue. METHODS: Ten normal healthy subjects volunteered for the study. All subjects were administered placebo, phenolphthalein (at doses of 15, 30, 45, 60, 75 and 90 mg) or phenolphthalein glucuronide (at equivalent doses of 24, 48, 72, 96, 120 and 144 mg) in a random order. Stool weight, the frequency and consistency of stools, and the development of symptoms were recorded at 12-h intervals for 84 h. RESULTS: There was a significant increase in the mean stool weight obtained within the first 24 h of administration of a 30 mg dose of phenolphthalein and its glucuronide equivalent compared to the values obtained with placebo. A further increase in the dose did not improve the therapeutic response. There was no difference between phenolphthalein and phenolphthalein glucuronide with respect to the rapidity of action, the threshold dose, effectiveness of laxation, or the frequency of adverse effects. CONCLUSIONS: The therapeutic response and side effect profile of the different doses favoured 30 mg phenolphthalein as the optimum laxative dose. Although theoretically superior, phenolphthalein glucuronide was not found to be a more effective laxative compared to phenolphthalein in normal subjects.

Cathartics↗
PubMed1994

How does Helicobacter pylori cause duodenal ulcer disease: the bug, the host, or both?

Helicobacter pylori infection is the most common cause of duodenal ulcer disease, yet duodenal ulcer is an uncommon outcome of H. pylori infection. We reviewed the possible explanations such as differences in the host or in the strain of H. pylori. Host factors reviewed included genetic susceptibility to H. pylori infection and excess gastric acid secretion. The role of potential H. pylori virulence factors not present in all strains such as the cagA gene and the results of other molecular methods to identify disease-specific differences among isolates was also reviewed. Although cure of H. pylori infection resolves gastrin releasing peptide stimulated acid secretion there was no change in parietal cell mass. Twin studies have shown genetic differences in H. pylori susceptibility. There was no difference in the prevalence of the cagA gene between H. pylori infected asymptomatic volunteers and duodenal ulcer patients (P = 1.0). DNA-DNA hybridization of whole genomic DNA in solution and cluster analysis of rep-PCR genomic DNA fingerprints suggest that isolates from patients with duodenal ulcer disease are different from those obtained from individuals with asymptomatic gastritis. Cluster analysis of the rep-PCR DNA fingerprints revealed two major groups of the strains; one set consisted of strains from patients with duodenal ulcer disease and the second cluster consisted largely of strains from individuals with asymptomatic gastritis. Recent molecular studies suggest that disease-specific cell lineages or strains may exist among H. pylori isolates leading to the various outcomes observed in patients with H. pylori infection.

DNA Fingerprinting↗
PubMed1994

Detection of immunoglobulin M (IgM), IgA, and IgG Norwalk virus-specific antibodies by indirect enzyme-linked immunosorbent assay with baculovirus-expressed Norwalk virus capsid antigen in adult volunteers challenged with Norwalk virus.

Pre- and postexposure sera collected from 17 adult volunteers challenged with Norwalk virus as described previously (D. Y. Graham, X. Jiang, T. Tanaka, A. Opekun, P. Madore, and M. K. Estes, J. Infect. Dis. 170:34-43, 1994) were examined for Norwalk virus-specific immunoglobulin M (IgM), IgA, and IgG by indirect enzyme-linked immunosorbent assays with recombinant Norwalk virus antigen bound to the solid phase. Sixteen of the 17 volunteers had evidence of past infection, all presenting with preexisting IgG antibody of high avidity; only one volunteer had no evidence of previous infection. Virus infection was detected in 14 of the 16 volunteers with evidence of past infection, and 9 of the infected volunteers had symptomatic illness. A significant rise in both virus-specific IgA and IgG titers was detected after challenge in all of the volunteers who became ill. Five of the asymptomatic volunteers who were infected had rising titers of virus-specific IgG, but only two of the five had a concomitant rise in their virus-specific IgA antibody titers. Antibody rises were detectable in eight of nine ill volunteers 8 to 11 days after challenge but in the asymptomatic volunteers only after more than 15 days had elapsed. Virus-specific IgM was detected after challenge in all 14 infected volunteers. Between symptomatic and asymptomatic volunteers there were no significant differences in titers of virus-specific IgG and IgA in serum before challenge; however, there were significantly higher titers in symptomatic volunteers between 8 and > 90 days after challenge for virus-specific IgG and 8 and 24 days after challenge for virus-specific IgA.

Adult↗
PubMed1994

Importance of childhood socioeconomic status on the current prevalence of Helicobacter pylori infection.

Helicobacter pylori infection is commoner in black and Hispanic people compared with age matched white people. H pylori status was evaluated using an enzyme linked immunosorbent assay for anti-H pylori IgG in 150 healthy black and Hispanic people aged between 19 and 49 years. All were employed and had completed high school at least. Socioeconomic status during childhood was estimated from the parents' education and occupation(s) using a modified Hollingshead index and family income. Five social classes were defined (class I = lowest, V = highest). The H pylori prevalence was inversely related to the social class during childhood. It was 85% for class I, 52% for combined classes II and III, and 11% for classes IV and V combined. The inverse correlation remained after adjustments were made for the present social class and age. H pylori infection was also related to crowded living conditions (odds ratio 4.5: 95% confidence interval 3.3, 5.7) for those who had had the most crowded living conditions during childhood). The increased prevalence of H pylori in black and Hispanic people seems to be related to low socioeconomic status in childhood. These data are also consistent with the suggestion that childhood is a period of major risk for H pylori infection.

Adult↗
PubMed1994

Peptic ulcer disease, Helicobacter pylori, and the surgeon: changing of the guard.

The ability to assign causative roles to Helicobacter pylori and nonsteroidal anti-inflammatory drug use in peptic ulcer disease, and proof that eradication of H. pylori infection results in cure of peptic ulcer disease, are resulting in a reassessment of the indications for surgery and the type of surgery to be performed. With only a few exceptions, surgery is rapidly becoming an outdated approach to the management of peptic ulcer disease. We will soon see the day when surgeons with great technical skill in peptic ulcer disease will be rare, just as it happened when chest surgeons were no longer needed for the management of chronic pulmonary infections.

Diagnosis, Differential↗
PubMed1994

Helicobacter pylori infection in Japan: current status and future options.

BACKGROUND: The combination of the high prevalence of Helicobacter pylori infection in Japan and the availability of methods to diagnose and treat the infection suggest that elimination of the infection from the population might be beneficial. Therefore we reviewed the epidemiology, consequences and possible benefits of elimination of H. pylori in Japan. RESULTS: H. pylori infection has been etiologically linked to peptic ulcer disease, gastric carcinoma and gastric B-cell lymphoma. The cumulative risk of those with H. pylori infection for developing peptic ulcer disease is 15-20%, with 0.01-0.1% developing gastric carcinoma. Twenty to thirty per cent of those infected suffer mortality or morbidity related to H. pylori infection. Recommendations were made concerning the elimination of this infection. CONCLUSIONS: Eradication of H. pylori should largely eliminate peptic ulcer disease with all its costs and complications, while rapidly changing the risk of developing gastric cancer.

Helicobacter Infections↗
PubMed1994

Infectious esophagitis.

This article presents the epidemiology, pathogenesis and pathology, clinical manifestations, and diagnosis and treatment of Candida, herpes simplex virus, cytomegalovirus, Mycobacterium tuberculosis, Aspergillus, histoplasmosis, blastomycosis, and HIV. Uncommon AIDS-related esophageal infections are also discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Are there susceptible hosts to Helicobacter pylori infection?

Susceptibility to Helicobacter pylori infection may manifest itself as an increased prevalence of H. pylori infection, as reinfection after eradication, or as different clinical outcomes (gastritis, peptic ulcer disease, primary gastric B-cell lymphoma, or gastric cancer). These outcomes are likely to be a result of interaction between environmental and genetic factors. Genetic factors include both host genetic predisposition to infection as well as genetic differences in H. pylori strains. Twin studies indicate that the correlation coefficient for the relative importance of genetic effects (heritability) on acquisition of H. pylori infection is approximately 0.66. The remaining variance is accounted for by shared rearing environmental factors (20%), and non-shared environmental factors (23%), which contribute to the differences and not the similarities seen between family members. Molecular epidemiological studies of both the whole bacterial genome and of amplified regions between specific repetitive DNA sequences also suggest that there are disease-specific strains of H. pylori. There are, therefore, many different facets of susceptibility to H. pylori infection.

Adult↗