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Biomedical subjects

D R Cave

Publications and source records attributed to D R Cave.

At least 19 recordsLinked to original sources

Helicobacter pylori-related disease: guidelines for testing and treatment.

OBJECTIVE: To develop practical guidelines for the treatment of patients with suspected and documented Helicobacter pylori-related gastroduodenal diseases. METHODS: A panel of physicians with expertise in H. pylori reviewed, critically appraised, and synthesized the literature on assigned topics and presented their overviews to the panel. Consensus was obtained in controversial areas through discussion. RESULTS AND CONCLUSIONS: The panel recommended testing for H. pylori in patients with active ulcers, a history of ulcers, or gastric mucosa-associated lymphoid tissue lymphomas. Young, otherwise healthy patients with ulcerlike dyspepsia and those with a family history or fear of gastric cancer may also undergo H pylori testing. Non-endoscopic methods are preferred for H. pylori diagnosis. Dual medication regimens should not be used for therapy; twice-daily triple therapy with a proton pump inhibitor or ranitidine bismuth citrate, clarithromycin, and amoxicillin for 10 to 14 days is an appropriate therapy. Posttreatment assessment of H. pylori status using urea breath testing should be considered in patients with a documented history of ulcer disease or with persistent symptoms.

Adenocarcinoma↗

Evaluation of a PCR primer based on the isocitrate dehydrogenase gene for detection of Helicobacter pylori in feces.

In order to improve detection and identification of Helicobacter pylori in highly contaminated samples, we evaluated new specific primers based on the DNA base sequence within the isocitrate dehydrogenase (icd) gene to amplify a 1,200-bp DNA segment. The specificity of the icd primer was tested against DNA derived from various bacteria, including 7 Helicobacter species and a panel of 1 gram-variable, 2 gram-positive, and 16 gram-negative bacteria, as well as DNA from houseflies and feces from H. pylori-negative patients. The primers permitted the detection of all clinical H. pylori isolates tested, but no reactions were observed with negative controls. Several procedures for DNA extraction from feces were evaluated using PCR with icd primers. The lower limits of detection of H. pylori DNA from two different sources containing the same number of H. pylori organisms, a pure culture and feces spiked with H. pylori, were established for each extraction method tested. The results were 8.0 x 10(3) CFU/ml for cultures of pure H. pylori, and 8.0 x 10(6) CFU/ml for H. pylori from feces, using the phenol-chloroform method; 8.0 x 10(2) and 7.0 x 10(3) CFU/ml, respectively, for a glass matrix and chaotropic solution protocol; 8.0 x 10(2) and 7.0 x 10(3) CFU/ml, respectively, for the QIAamp tissue kit; and 5.0 x 10(2) and 5.0 x 10(3) CFU/ml, respectively, for the XTRAX DNA extraction kit. We conclude that the use of the icd gene as a primer for PCR represents a specific and sensitive assay for detection of H. pylori in highly contaminated samples.

Animals↗

Efficacy of a 1-week regimen of ranitidine bismuth citrate in combination with metronidazole and clarithromycin for Helicobacter pylori eradication.

BACKGROUND: In order to improve the efficacy and simplicity of the FDA-approved regimen of ranitidine bismuth citrate (RBC) and clarithromycin dual therapy, we added an inexpensive antibiotic (metronidazole), changed the dosage scheme to twice daily dosing, and decreased the duration of therapy to 1 week. METHODS: This was an open label study in which subjects with previously untreated Helicobacter pylori infection documented by serology or endoscopy and confirmed by the 13C-urea breath test received a 1-week course of RBC 400 mg b.d., metronidazole 500 mg b.d. and clarithromycin 500 mg b.d. A repeat breath test was performed 4-6 weeks after completing therapy. RESULTS: Forty-seven out of 50 subjects completed the protocol. Intention-to-treat and per protocol cure rates were 86% and 91%, respectively. The regimen was well tolerated. Study drugs were stopped in two patients due to side-effects. The most common side-effect was self-limited diarrhoea. CONCLUSION: Twice daily RBC-based triple therapy with metronidazole and clarithromycin for 1 week is well tolerated and effective in eradicating H. pylori infection.

Anti-Bacterial Agents↗

A multicentre evaluation of the laser assisted ratio analyser (LARA): a novel device for measurement of 13CO2 in the 13C-urea breath test for the detection of Helicobacter pylori infection.

BACKGROUND: The laser assisted ratio analyser (LARA) was developed as a novel device to measure 13CO2 in the urea breath test for the detection of H. pylori infection. The analyser was tested in a prospective multicentre study in 444 patients in North America (Phase 1) followed by second study involving 160 patients (Phase 2). METHODS: Patients undergoing endoscopy for clinical indications had antral and gastric biopsies taken for histological examination, culture and CLO test. One hour after endoscopy, a baseline breath sample was obtained, 100 mg of 13C-urea were ingested and breath samples were obtained at 30 and 60 min post ingestion. Data obtained with the LARA were compared with the results of culture, rapid urease testing and central pathology in two different combinations {reference standards}. The study was conducted in two phases: in Phase 2, a modification was made to the LARA that improved the removal of water vapour from the breath sample. RESULTS: In Phase I, data from 331 patients were analysed using a cut off of (delta) 7.8 +/- 0.8, the sensitivity of the method was 91.7% and the specificity was 86.5%, using the reference standard of 2 of 3 tests (CLO, culture or histology) being positive. Positive and negative predictive values were, respectively, 85.2% and 92.5%. In Phase 2 of the study, 160 patients were enrolled and 141 patients were analysed using the same standards. We used the same reference standards but with a cut off of (delta) 6.1 +/- 0.6. The sensitivity and specificity increased to 96.8% and 98.6%, respectively. Positive and negative predictive values were, respectively, 98.4% and 97.3%. The detection rates for H. pylori were similar in patients with peptic ulcer or H. pylori associated gastritis. CONCLUSIONS: The LARA provides an accurate non-invasive means of detecting 13CO2 in the 13C-urea breath test for H. pylori in a multicentre clinical environment that compares well with invasive 'gold standard' methods.

Adolescent↗

Factors affecting solubility and penetration of clarithromycin through gastric mucus.

BACKGROUND: Factors influencing the pharmacokinetics of clarithromycin in gastric mucus are poorly defined. AIM: To determine: (i) whether the clinical formulation of clarithromycin (Biaxin granules and powdered Biaxin tablets) affects the water solvency of the antibiotic or changes the barrier properties of pig gastric mucus (PGM), thereby influencing the penetration of clarithromycin through the gastric mucus layer; and (ii) whether topically active anti-ulcer agents affect clarithromycin penetration through gastric mucus. METHODS: Solubility of clarithromycin in aqueous solution was studied at pH 7. PGM viscosities were determined using a falling ball microviscometer. Permeability of clarithromycin through PGM with and without added anti-ulcer drugs at pH 7 was monitored using a microfiltration device and an agar diffusion bioassay. RESULTS: Clarithromycin showed the poorest solubility at pH 7, whereas both Biaxin formulations demonstrated identical solubility of their antibiotic ingredient. Clarithromycin and both Biaxin formulations markedly increased mucin viscosity over the pH range 2-7. PGM markedly retarded the penetration of clarithromycin: unformulated clarithromycin and Biaxin tablets penetrated more rapidly through mucus than Biaxin granules. Pre-treatment of PGM with aluminium-magnesium-containing antacids (Riopan and Talcid preparations) decreased the rate of clarithromycin penetration, whereas Carafate and Peptobismol had no significant effect on mucus penetration of clarithromycin. CONCLUSIONS: The availability of clarithromycin in gastric mucus is significantly influenced by its clinical formulation, which affects its solubility as well as the viscous properties of mucus. Pulverized Biaxin tablets provide better local distribution of clarithromycin in mucus than Biaxin granules. Pre-treatment of mucus with anti-ulcer medications does not increase the penetration of clarithromycin through mucus.

Absorption↗

Helicobacter pylori--more light, less heat.

Several areas of broad agreement exist concerning the management of specific patient groups with clear-cut complications of H. pylori-colonization. Other aspects of this infection remain less well defined. These include the mode of transmission and pathogenesis of H. pylori, the clinical management of patients who do not have ulcer disease, and the approach to populations at risk of the clinical consequences of this bacterium. This review focuses on the unresolved issues of H. pylori infection that are of concern to the clinical gastroenterologist.

Disease Models, Animal↗

[Flies--reservoirs and vectors of Helicobacter pylori].

The route by which humans get infected with H.p. is unknown. Viable bacteria have been shown to be excreted in human feces from infected individuals. We have recently shown that flies are able to carry and disseminate viable H. p. with their excreta, when they have fed on H.p. We propose a hypothesis that H. p. is acquired from human feces by flies, which then, while crawling on human food, contaminate it with their intestinal excreta. The food, swallowed by a susceptible individual then leads to a new infection. Flies should be considered prime suspects for the transmission of H. p., particularly in developing countries, where sanitary and domestic facilities are poor.

Animals↗

How is Helicobacter pylori transmitted?

Helicobacter pylori is one of the world's most common pathogens. It colonizes about 60% of the world's population, causes gastritis and peptic ulcer, and is strongly associated with gastric adenocarcinoma and lymphoma. However, most individuals never develop clinical disease. Thirteen years after the culture of H. pylori by Marshall and Warren, we still do not know its major mode of transmission. Childhood represents the major period of acquisition of infection in the third world, but infection is rare in children in the developed world. Possible routes of infection include either oral-oral or fecal-oral, iatrogenic spread with inadvertent use of unsterile pH probes and endoscopes, and vectorial spread by flies. Evidence to support each route of transmission is provided, but there is no predominant route. The only significant reservoir of infection appears to be humans themselves. The organism has been found in some domestic cats and in nonhuman primates, but the opportunities for human interaction with the latter are rare, making infection from this source an unlikely possibility. The organism has the propensity to become a coccoid form. This may represent a persistent form in which H. pylori can exist in the environment, but it has yet to be shown that it can revert to the replicative form.

Animals↗

Interaction of an aluminum-magnesium containing antacid and gastric mucus: possible contribution to the cytoprotective function of antacids.

BACKGROUND: Antacids are generally thought to protect the gastric mucosa from damage primarily by their ability to neutralize hydrochloric acid, but recently other mechanisms of antacid cytoprotection have been suggested. The aim of our study was to determine if the antacid hydrotalcit (Mg6Al2(OH)16CO3 x 4H2O) and its clinical formulations Talcid (suspension and tablet) can influence the acid barrier properties of pig gastric mucus (PGM). METHODS: Viscosities, flow patterns of injected HCl, and permeability to HCl were assayed in solutions of PGM with and without added antacid. RESULTS: Talcid-suspension markedly increased mucin viscosity between pH 2 and 7. In contrast, powdered Talcid-tablet and hydrotalcit noticeably reduced mucin viscosity at pH 5 and below. HCl barely diffused through PGM-Talcid-suspension, whereas the acid was able to quickly penetrate a PGM-Talcid-tablet powder or PGM-hydrotalcit mixture. When injected into a mixture of PGM-Talcid-suspension, HCl travelled in a single distinct channel whereas in both PGM-Talcid-tablet powder or PGM-hydrotalcit mixtures, the acid mixed irregularly throughout. Experiments with antacids alone revealed that Talcid-suspension, but not Talcid-tablet nor hydrotalcit, had barrier properties similar to PGM. CONCLUSION: Talcid-suspension has viscoelastic features similar to gastric mucin and may afford mucosal protection by its ability to maintain or mimic the barrier properties of gastric mucus gel. In contrast, powdered Talcid-tablets and hydrotalcit reduce the barrier function of gastric mucus.

Aluminum Hydroxide↗

Vector potential of houseflies (Musca domestica) for Helicobacter pylori.

The mode of transmission of Helicobacter pylori is unknown. Since viable bacteria have been shown to be excreted in feces from infected individuals and houseflies habitually develop and feed on excrement, we hypothesized that flies ingest and harbor H. pylori and, in turn, contaminate the human environment. This study examined the possible vector potential of houseflies (Musca domestica) for H. pylori. Caged houseflies were exposed to freshly grown H. pylori on agar plates. After a 6-h feeding period, the plates were removed and were replaced with sterile petri dishes containing a droplet of sterile brucella broth. At regular intervals, small numbers of houseflies were removed for microbiological and histological analysis, and the petri dishes were replaced with fresh sterile plates with fresh drops of brucella broth. The flies' bodies, the flies' dissected alimentary tracts, and excreta on the petri dishes were cultured for H. pylori, whose identity was confirmed by the urease, catalase, and oxidase reactions and Gram staining. In contrast to control flies, viable H. pylori could be isolated from external surfaces for up to 12 h and from gut and excreta for as long as 30 h after the initial feeding period. After 30 h other gram-negative bacteria overgrew the cultures of samples from all locations tested, rendering the selective culture of H. pylori colonies impossible. Histological analysis revealed Helicobacter-like organisms in the gut lumen and attached to intestinal epithelial cells. We conclude that houseflies can harbor viable H. pylori on their bodies and in their intestinal tracts. They are also able to disseminate viable H. pylori in excreta, and they may therefore present a significant reservoir and be a vector in the transmission of H. pylori.

Animals↗

Transmission and epidemiology of Helicobacter pylori.

Helicobacter pylori is one of the most common bacterial infections worldwide. However, the majority of those infected do not develop clinical manifestations of disease. This review discusses the epidemiology of the organism in terms of incidence and prevalence, the presumed means of transmission from person to person, and how typing of the organism has helped the epidemiologist. The epidemiology of disorders that are associated with H. pylori is also discussed.

Helicobacter Infections↗

Management of Helicobacter pylori infection in ulcer disease.

Eradication of the bacterium not only heals the ulcer but essentially cures the underlying peptic ulcer disease. Although there is still no simple, all-purpose regimen, a decade of experience has identified safe, well- tolerated drug combinations that yield eradication rates exceeding 90% without generating a high frequency of bacterial resistance.

Anti-Bacterial Agents↗

Complete intraoperative small-bowel endoscopy in the evaluation of occult gastrointestinal bleeding using the sonde enteroscope.

OBJECTIVE: To review our experience with intraoperative small-bowel Sonde enteroscopy in evaluating occult bleeding in the small intestine. DESIGN: Retrospective study with 100% follow-up. SETTING: University-affiliated, tertiary-care teaching hospital. PATIENTS: Sixteen consecutive patients referred with occult gastrointestinal bleeding in whom esophagogastro-duodenoscopy , push enteroscopy, and colonoscopy had failed to identify the source of bleeding. Fourteen of the 16 patients had required one or more transfusions. MAIN OUTCOME MEASURE: Completeness of visualization, diagnostic accuracy, and complications of the procedure and follow-up for recurrent bleeding. RESULTS: In all 16 patients, intraoperative Sonde enteroscopy allowed visualization of the entire small bowel. In 14 of the 16, it revealed the cause of bleeding, which was ileal angiodysplasia in three patients, ileal ulcers in six patients, neoplasia in two patients, and ileal ulcers caused by Crohn's disease, small-intestinal enteropathy and varices caused by portal hypertension, and radiation stricture in one patient each. Two patients had normal small bowel mucosa. The patients with mucosal disease underwent small-bowel resection or oversewing of bleeding sites. Two surgical complications occurred: prolonged postoperative ileus (one patient) and small-bowel obstruction that resolved without surgery (one patient). Two of the patients with angiodysplasia had recurrent bleeding postoperatively. CONCLUSIONS: Intraoperative Sonde enteroscopy is safe and effective in localizing small-intestinal bleeding sites, providing complete visualization of the small-bowel mucosa without enterotomy while avoiding the trauma that can be caused by push endoscopy. It is the diagnostic assessment of choice in selected patients with occult gastrointestinal bleeding of presumed small-bowel origin.

Adult↗

One-stage retrograde approach to Nd:YAG laser palliation of esophageal carcinoma.

BACKGROUND AND STUDY AIMS: The aim of the present study was to determine the safety, efficacy, and feasibility of a one-stage retrograde approach to Nd:YAG laser palliation of esophageal carcinoma carried out under general anesthesia. PATIENTS AND METHODS: Endoscopic Nd:YAG laser therapy was used on 150 occasions in 62 consecutive patients with advanced malignant obstruction of the esophagus. All procedures were carried out under general anesthesia. The lesion was first dilated using a Savary-Gilliard dilator or balloon technique, and the endoscope was then passed beyond the lesion. Laser energy was applied to the lesion in a circumferential manner as the scope was withdrawn along the length of the lesion, until an adequate lumen was established. RESULTS: Ninety-three percent of the patients had symptomatic improvement, defined as reduction in the subjective dysphagia grade, and only 14% of the patients required repeat procedures within 30 days. Fifty percent of the patients experienced effective palliation with only one procedure over the entire course of their illness. In patients with recurrent dysphagia, the mean time between procedures was 100 days. Seventy-six percent of the patients were discharged on the day following the procedure. Complications included the development of pneumomediastinum or subcutaneous emphysema in five cases, and esophageal perforation in two cases. All cases of pneumomediastinum or subcutaneous emphysema or perforation were managed by conservative therapy. Hemorrhage requiring transfusion occurred in two cases. There were three apparently procedure-related deaths occurring within 30 days of the initial procedure. CONCLUSIONS: Effective palliation of obstructing esophageal carcinoma can be achieved in one session using a one-stage retrograde approach with the Nd:YAG laser under general anesthesia. When compared to other palliative modalities, this method produces a longer dysphagia-free interval, and patients with a terminal illness are therefore able to spend more time out of hospital.

Adult↗

Intraoperative enteroscopy. Indications and techniques.

This article reviews the role on intraoperative enteroscopy (IOE) in the management and evaluation of patients with chronic transfusion-dependent gastrointestinal bleeding who have not responded to standard diagnostic and therapeutic techniques. Intraoperative enteroscopy may be performed with a standard or pediatric colonoscope, push enteroscope, or a sonde enteroscope at the time of laparotomy. IOE techniques as well as indications, diagnostic and therapeutic capabilities, and complications of this procedure are discussed.

Diagnosis, Differential↗