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Biomedical subjects

J R Warren

Publications and source records attributed to J R Warren.

At least 37 records · Page 2Linked to original sources

Enterococcus faecium and Enterococcus faecalis bacteremia: acquisition and outcome.

The incidence of enterococcal bacteremia due to Enterococcus faecium is increasing. To understand the clinical significance of E. faecium bacteremia, we compared 16 patients who were bacteremic due to E. faecium to 56 patients who were bacteremic due to Enterococcus faecalis. E. faecium bacteremia developed most frequently in severely ill patients with fever or hypothermia accompanied by CNS, cardiovascular, and/or pulmonary dysfunction, while E. faecalis bacteremia occurred most often in less seriously ill patients. Nosocomial acquisition, cancer, neutropenia, renal insufficiency, current corticosteroid therapy, and previous treatment with broad-spectrum antibiotics were significantly more frequently associated with E. faecium bacteremia. Mortality was significantly higher among patients infected with E. faecium than among those infected with E. faecalis (50% vs. 11%; P = .001); this was true particularly among patients with monomicrobial or nosocomial bacteremia, those who had previously received antibiotic treatment, and those with cancer. Death due to enterococcal bacteremia was observed only among severely ill patients. These findings suggest that E. faecium often infects debilitated patients and that such infection appears to be a significant factor contributing to mortality.

Bacteremia↗

Duodenal ulcer treated with Helicobacter pylori eradication: seven-year follow-up.

The long-term benefits of Helicobacter pylori-eradication treatment (HET) in H pylori-associated duodenal ulcer are unclear. We followed up patients with duodenal ulcers from a trial of H pylori eradication in 1985-86. 63 of 78 patients (81%) were reviewed clinically and had upper gastrointestinal endoscopy with gastric antral biopsy. Of 35 patients previously rendered H pylori negative, 32 (92%) remained H pylori negative after 7.1 years (mean). All patients initially H pylori positive remained infected, unless HET was given in the interim. Duodenal ulceration was found in 20% (5 out of 25) of patients remaining H pylori-positive, compared with 3% (1 of 38) of H pylori-negative patients (p < 0.05). The reduction of duodenal ulcer relapse obtained from H pylori eradication in H pylori-associated duodenal ulcer extends to at least 7 years after treatment, and is likely to be due to freedom from H pylori infection. However, duodenal ulcer may recur in patients rendered H pylori negative, due to factors other than reinfection with H pylori.

Adult↗

Bactericidal activity of the fluoroquinolone WIN 57273 against high-level gentamicin-resistant Enterococcus faecalis.

The fluoroquinolone WIN 57273 showed identical bactericidal activities (MBC for 90% of the strains = 0.25 micrograms/ml) for bacteremic strains of Enterococcus faecalis with and without high-level gentamicin resistance. WIN 57273 was bactericidal in time-kill measurements with highly gentamicin-resistant, ciprofloxacin-susceptible strains of E. faecalis. However, WIN 57273 was indifferent with penicillin for gentamicin-resistant E. faecalis and was not bactericidal for ciprofloxacin-resistant E. faecalis.

Anti-Infective Agents↗

When is Helicobacter pylori infection acquired?

Cross sectional surveys have shown an increasing prevalence of Helicobacter pylori (H pylori) infection with increasing age in Western populations. The aim of this study was to examine the pattern of acquisition of H pylori infection over a 21 year period in a group of 141 adults who had blood samples and serum stored in 1969, 1978, and 1990. A prevalence of H pylori antibody of 39% in 1969 serum samples, 40.9% in 1978, and 34.8% in 1990 was found when assessed by an enzyme linked immunosorbent assay (ELISA). Of the 86 subjects who were seronegative in 1969, only six (7%) were seropositive in 1990. These data suggest that a cohort effect may contribute to the pattern of increasing prevalence of H pylori infection seen with increasing age. Acquisition of infection in adults is rare. It is unlikely, therefore, that reinfection will occur after successful eradication.

Adult↗

Inhibition of preimplantation mouse embryo development by isoflurane.

OBJECTIVE: Preimplantation mouse embryos were exposed to a commonly used inhalational anesthetic agent, isoflurane, to determine its effects on embryo development. STUDY DESIGN: Two-cell embryos were exposed at various intervals (5 to 6 hours, 3 to 4 hours, and 0 to 1 hour) before the onset of their first cleavage in vitro. In addition, the effects of 5% isoflurane on four-cell embryos exposed about 2 hours after the first cleavage and morula stage embryos also were examined. RESULTS: Development to the blastocyst stage was inhibited by 3% and 5% isoflurane (p less than 0.005) but not by 1.5% isoflurane when two-cell embryos were exposed 3 to 4 hours or 0 to 1 hour before the onset of cleavage. Most of the affected embryos completed cell division and came to a halt at the three- to four-cell stage. The development of embryos exposed to isoflurane at the four-cell or morula stage was unaffected. CONCLUSIONS: Isoflurane adversely affects subsequent preimplantation development when two-cell mouse embryos are exposed just before the onset of their first cleavage in vitro.

Animals↗

High-level gentamicin resistance in Enterococcus faecalis bacteremia.

In a retrospective analysis, patients with bacteremia due to Enterococcus faecalis with and without high-level gentamicin resistance (GRE; MIC greater than 2000 micrograms/ml) were compared. Bacteremic patients with GRE (n = 32) had significantly higher rates of nosocomial acquisition and bladder catheterization, longer hospitalizations, and more frequent prior treatment with cephalosporins than did bacteremic patients without high-level resistance (n = 19). Overall mortality was significantly associated with septic shock, high-risk source (intraabdominal, wound, respiratory tract, multiple, unknown), and polymicrobial bacteremia. Higher mortality was observed in GRE bacteremia (47%) than in bacteremia without high-level resistance (37%), but this difference was not statistically significant. For patients with monomicrobial bacteremia, low-risk source (genitourinary tract, intravascular), or treatment with antibiotics appropriate for the enterococcus, higher mortality with GRE bacteremia approached statistical significance. These results suggest that high-level resistance adversely affects survival with a pure E. faecalis bacteremia or low-risk bacteremic source. Also, response to antibiotic therapy may be diminished by high-level resistance.

Adult↗

Effects of nitrous oxide on preimplantation mouse embryo cleavage and development.

Preimplantation mouse embryos were exposed to nitrous oxide for 30 min to determine its effects on subsequent development after short durations of exposure. Two-cell mouse embryos were exposed to 60% nitrous oxide/40% oxygen at 6-7 h, 3-4 h, or 0-1 h prior to the expected onset of their first cleavage in vitro, or at the 4-cell or morula stages. Effects of nitrous oxide were not observed except in 2-cell embryos treated within 4 h of the expected in vitro cleavage. At 3-4 h and 0-1 h prior to the onset of cleavage, exposure to 60% nitrous oxide/40% oxygen resulted in blastocyst development rates of 27.7% and 4.7%, respectively, while control rates ranged from 75% to 77%. The majority of affected embryos were halted at the 2-cell stage before completing cell division. Similar effects were obtained with 80% nitrous oxide/20% oxygen. Thus, we conclude that brief exposure of mouse preimplantation embryos to nitrous oxide may be deleterious to subsequent embryo cleavage, but this effect is highly dependent on the developmental stage at which exposure occurs.

Animals↗

The 14C-urea breath-test for the detection of gastric Campylobacter pylori infection.

A breath-test has been developed for the detection of gastric infection with Campylobacter pylori. Urea that is labelled with carbon 14 is administered to a fasting patient and the patient's breath is sampled for radioactivity over the following 30 minutes. If C. pylori is present in the patient's stomach, urease activity causes hydrolysis of the urea and the 14C is absorbed as carbon dioxide. This carbon dioxide enters the patient's bicarbonate pool and eventually is excreted in the breath. The results are expressed as a percentage of the administered dose/mmol carbon dioxide x kg body weight. Sixty-three patients who were undergoing endoscopy were studied. The radioactivity in exhaled breath which was sampled within five minutes of 14C-urea administration was attributed to the presence of urease enzyme in mouth organisms and was discounted. The time-radioactivity curves for breath samples from five to 30 minutes after the administration of 14C-urea gave an excellent separation between subjects with negative results of the examination of gastric-biopsy samples and patients with microbiological and histological evidence of infection with C. pylori. The area under the time-radioactivity curve at between five and 30 minutes after the administration of 14C-urea in 24 patients with negative microbiological results was 6.9 +/- 4.4 area units; in 35 of 39 patients with positive microbiological results, this area was greater than 40 area units. Measured against the results of the microbiological examination of gastric-biopsy samples, the sensitivity of breath-testing was 90% and the specificity was 100%. Measured against the results of histological examination for the presence of C. pylori infection, breath-testing had a sensitivity of 94% and a specificity of 93%. A positive breath-test result also correlated well (P = 0.0001) with the serological antibody test-result. The role of non-invasive tests--enzyme-linked immunosorbent assays and 14C-urea breath-testing--in the management of gastritis and peptic ulcer disease is discussed. We consider that the 14C-urea breath-test has an important role in the noninvasive confirmation of gastric infection with C. pylori and in the follow-up of patients after treatment.

Adult↗

Stimulation of epithelial hyperplasia in rat urinary bladder by Escherichia coli cystitis.

Using heterotopically transplanted rat urinary bladder, experiments were conducted to develop a reproducible animal model of bacterial cystitis-associated urothelial hyperplasia without calculus formation, and to elucidate which bacterial component(s) might induce urothelial hyperplasia. Bladder instillation of live Escherichia coli (E. coli) resulted in persistent infection and inflammation and also diffuse urothelial hyperplasia. Instillation of killed E. coli also induced diffuse hyperplasia. Hyperplastic changes regressed following withdrawal of the killed E. coli treatment. Urothelial hyperplasia was also induced by repeated instillation of protein-rich lipopolysaccharide (LPS), the endotoxin derived from gram-negative bacterial wall component, but not by protein-free LPS. A finding common to bladders showing hyperplasia was the infiltration of neutrophils into intercellular spaces of the urothelium. We conclude that urothelial hyperplasia is induced by E. coli cystitis, that LPS plays a significant role in the hyperplastic response, and that neutrophils may mediate the response.

Animals↗

The pulmonary clearance of smooth and rough strains of Pseudomonas aeruginosa.

Upper airway colonization with rough strains of Pseudomonas is associated with clinical deterioration in patients with cystic fibrosis. These rough strains are less toxic than smooth strains in the burned mouse model and in vitro assays. We measured the 4-h pulmonary clearance of 10(4) and 10(6) rough and smooth Pseudomonas after intrabronchial inoculation. After 10(4) Pseudomonas, rough strains were cleared more efficiently than smooth strains (89 +/- 13% versus 140 +/- 19% of the original inoculum, respectively, p less than 0.05). This was associated with more total bronchoalveolar lavage PMNs after inoculation with rough as compared with smooth Pseudomonas (1.60 +/- 0.38 x 10(5) versus 0.55 +/- 0.09 x 10(5), respectively, p less than 0.05). After inoculation with 10(6) Pseudomonas, rough were cleared less efficiently than smooth Pseudomonas (380 +/- 45% versus 134 +/- 12% of the original inoculum, respectively, p less than 0.05). There was no difference in the BAL PMNs of the animals inoculated with either bacterial strain at this inoculum (8.1 +/- 0.6 x 10(5) and 9.4 +/- 1.0 x 10(5) for the rough and smooth Pseudomonas, respectively). When PMN differences were abolished in C5-deficient mice, 10(4) rough were cleared less efficiently than smooth Pseudomonas. The relatively poor clearance of rough Pseudomonas could not be explained by in vitro differences in PMN killing or BAL toxicity or by intrinsic growth rates.

Animals↗

Free calcium and calmodulin levels in acinar carcinoma and normal acinar cells of rat pancreas.

Exposure of acinar carcinoma cells and normal acinar cells of rat pancreas to the muscarinic agonist drug carbamylcholine stimulated 45Ca2+ outflux from 45Ca2+-labeled cells. More rapid outflux of 45Ca2+ was detected for carcinoma cells following muscarinic stimulation than for normal cells. Direct fluorometric measurement of cytosolic Ca2+ under basal (unstimulated) conditions in quin 2-loaded cells revealed significantly lower concentration of free Ca2+ in carcinoma cells (approximately 180 nM) than in normal cells (approximately 200 nM). Stimulation with 1 mM carbamylcholine increased the cytosolic Ca2+ concentration in carcinoma and normal cells to approximately 1900 nM, after which carcinoma cells removed cytosolic Ca2+ at a faster rate to a post-stimulation plateau concentration of approximately 140 nM, in comparison to normal cells which obtained a post-stimulation plateau concentration of approximately 300 nM. Essentially identical differences between carcinoma and normal cells were detected upon stimulation with the peptidergic agonist cholecystokinin octapeptide. Finally, carcinoma cells demonstrated approximately 3 times greater calmodulin concentration than normal acinar cells. Also, the calmodulin antagonist drug W7 (N-6-(aminohexyl)-5-chloro-1-naphthalene sulfonamide) inhibited the carbamylcholine-induced release of intracellular Ca2+ in acinar carcinoma cells. These results indicate that neoplastic pancreatic acinar cells have retained mechanisms of muscarinic- and peptidergic-stimulated intracellular Ca2+ release, and implicate calmodulin as a regulatory factor in secretagogue activation of intracellular Ca2+ release. We propose that the more rapid decline of intracellular Ca2+ concentration following muscarinic or peptidergic stimulation and the increased intracellular calmodulin concentration indicate calmodulin-mediated down-regulation of free cytosolic Ca2+ in acinar carcinoma cells to levels lower than those of normal cells.

Animals↗

Failure of the Bactec 460 radiometer to detect Cryptococcus neoformans fungemia in an AIDS patient.

Cryptococcus neoformans fungemia occurred in a patient with the acquired immunodeficiency syndrome (AIDS). The BACTEC 460 radiometer failed to detect Cryptococcus neoformans in eight aerobic BACTEC 6B culture bottles inoculated with the patient's blood. The diagnosis of cryptococcemia was established by terminal (seven-day) subculturing of 6B broth to chocolate agar, which was positive for all eight radiometrically negative blood culture bottles. It appears that radiometric measurement is not optimal for the laboratory detection of cryptococcal fungemia.

Acquired Immunodeficiency Syndrome↗

Enzyme-linked immunosorbent assay for Campylobacter pyloridis: correlation with presence of C. pyloridis in the gastric mucosa.

Antibody to Campylobacter pyloridis was measured by ELISA in the sera of 160 patients from whom gastric biopsy specimens were also obtained. The antigen was an acid-glycine extract of C. pyloridis, and titers ranged from 80 to 22,000 ELISA units (EU). Of 117 patients in whom C. pyloridis was detected microbiologically or histologically, 87 (74%) had a titer greater than or equal to 300 EU, and only one had a titer less than 150 EU. Of 43 patients in whom C. pyloridis was not detected, only two (5%) had a titer greater than 300 EU. Thus, for a titer of 300 EU the ELISA test had a specificity of 97% and a sensitivity of 81%. At 150 EU the specificity was 78%, and the sensitivity was 99%. Histological diagnosis of active chronic gastritis was associated with a high median ELISA titer (485 E), chronic gastritis with a much lower titer (150 EU), and normal histology with a titer of 110 EU. Discriminating use of this serological test could be of assistance to detect C. pyloridis in the gastric mucosa.

Adult↗