Adverse events associated with bidirectional endoscopy with midazolam and pethidine.

Same-day bidirectional endoscopy has been reported to reduce recovery time, and procedure-related cost. The safety of bidirectional endoscopy vs colonoscopy only, while using midazolam and pethidine, has never been evaluated. We reviewed 1,202 consecutive patients who underwent bidirectional endoscopy or colonoscopy only with administration of midazolam and pethidine in Toyoshima Ensdoscopy Clinic. We compared the clinical characteristics and adverse events associated with method of endoscopy (colonoscopy only vs bidirectional endoscopy). Furthermore, multivariate logistic regression analyses were conducted to study the role of age, sex, use of sedative, polypectomy, and bidirectional endoscopy in adverse events. In the bidirectional endoscopy group, the doses of pethidine and midazolam, and the incidence rates of hypoxia and posto-endoscopic nausea were significantly higher. On multivariate analysis, age (odds ratio = 1.061, p<0.001), use of pethidine (odds ratio = 4.311, p = 0.003), and bidirectional endoscopy (odds ratio = 3.658, p<0.001) were independently associated with hypoxia. On multivariate analysis, female sex (odds ratio = 10.25, p = 0.027) and bidirectional endoscopy (odds ratio = 6.051, p = 0.022) were independently associated with post-endoscopic nausea. In conclusion, bidirectional endoscopy could increase hypoxia in elderly patients using pethidine and post-endoscopic nausea in female patients.

Dose-response model for Listeria monocytogenes-induced stillbirths in nonhuman primates.

A dose-response model using rhesus monkeys as a surrogate for pregnant women indicates that oral exposure to 10(7) CFU of Listeria monocytogenes results in about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a single dose of 10(2) to 10(10) CFU of L. monocytogenes had stillbirths. A log-logistic model predicts a dose affecting 50% of animals at 10(7) CFU, comparable to an estimated 10(6) CFU based on an outbreak among pregnant women but much less than the extrapolated estimate (10(13) CFU) from the FDA-U.S. Department of Agriculture-CDC risk assessment using an exponential curve based on mouse data. Exposure and etiology of the disease are the same in humans and primates but not in mice. This information will aid in risk assessment, assist policy makers, and provide a model for mechanistic studies of L. monocytogenes-induced stillbirths.

Comparison of Listeria monocytogenes virulence in a mouse model.

Listeriosis results from exposure to the foodborne pathogen Listeria monocytogenes. Although many different strains of L. monocytogenes are isolated from food, no definitive tests currently predict which isolates are most virulent. The objectives of this study were to address two major data gaps for risk assessors, variability among L. monocytogenes strains in pathogenicity and virulence. Strains used in our monkey clinical trial or additional food isolates were evaluated for their virulence and infectivity in mice. All strains were equally pathogenic to immunocompromised mice, causing deaths to 50% of the population 3 days after exposure to doses ranging from 2 to 3 log CFU. Doses resulting in 50% deaths on the fifth day after administration were 1 to 2 log lower than those on the third day, indicating that the full course of pathogenicity exceeds the 3-day endpoint in immunocompromised mice. Three strains were chosen for further testing for their virulence and infectivity in liver and spleen in normal (immunocompetent) mice. Virulence was not significantly different (P > 0.05) among the three strains, all resulting in deaths to 50% of mice at 5 to 7 log CFU by 5 days after administration. All strains were equally infective in liver or spleen, with higher numbers of L. monocytogenes directly correlated with higher doses of administration. In addition, there was no preference of organs by any strains. The lack of strain differences may reflect the limitation of the mouse model and suggests the importance of using various models to evaluate the pathogenicity and virulence of L. monocytogenes strains.

Cross-contamination between processing equipment and deli meats by Listeria monocytogenes.

Contamination of luncheon meats by Listeria monocytogenes has resulted in outbreaks of listeriosis and major product recalls. Listeriae can survive on processing equipment such as meat slicers which serve as a potential contamination source. This study was conducted to determine (i) the dynamics of cross-contamination of L. monocytogenes from a commercial slicer and associated equipment onto sliced meat products, (ii) the influence of sample size on the efficacy of the BAX-PCR and U.S. Department of Agriculture-Food Safety and Inspection Service enrichment culture assays to detect L. monocytogenes on deli meat, and (iii) the fate of L. monocytogenes on sliced deli meats of different types during refrigerated storage. Three types of deli meats, uncured oven-roasted turkey, salami, and bologna containing sodium diacetate and potassium lactate, were tested. A five-strain mixture of L. monocytogenes was inoculated at ca.10(3) CFU onto the blade of a commercial slicer. Five consecutive meat slices were packed per package, then vacuum sealed, stored at 4 degrees C, and sampled at 1 and 30 days postslicing. Two sample sizes, 25 g and contents of the entire package of meat, were assayed. Total numbers of L. monocytogenes-positive samples, including the two sample sizes and two sampling times, were 80, 9, and 3 for turkey, salami, and bologna, respectively. A higher percentage of turkey meat samples were L. monocytogenes positive when contents of the entire package were assayed than when the 25-g sample was assayed (12.5 and 7.5%, respectively). Lower inoculum populations of ca. 10(1) or 10(2) CFU of L. monocytogenes on the slicer blade were used for an additional evaluation of oven-roasted turkey using two additional sampling times of 60 and 90 days postslicing. L. monocytogenes-positive samples were not detected until 60 days postslicing, and more positive samples were detected at 90 days than at 60 days postslicing. When BAX-PCR and enrichment culture assays were compared, 12, 8, and 2 L. monocytogenes-positive samples were detected by both the enrichment culture and BAX-PCR, BAX-PCR only, and enrichment culture only assays, respectively. The number of L. monocytogenes-positive samples and L. monocytogenes counts increased during storage of turkey meat but decreased for salami and bologna. Significantly more turkey samples were L. monocytogenes positive when the contents of the entire package were sampled than when 25 g was sampled. Our results indicate that L. monocytogenes can be transferred from a contaminated slicer onto meats and can survive or grow better on uncured oven-roasted turkey than on salami or bologna with preservatives. Higher L. monocytogenes cell numbers inoculated on the slicer blade resulted in more L. monocytogenes-positive sliced meat samples. In addition, the BAX-PCR assay was better than the enrichment culture assay at detecting L. monocytogenes on turkey meat (P < 0.05).

Pathogenicity of food and clinical Listeria monocytogenes isolates in a mouse bioassay.

Serotype distributions of Listeria monocytogenes in clinical samples and foods often differ. It is unknown whether such differences reflect a variation in the virulence of strains or are due to other factors that are not directly related to the strains' ability to cause illnesses. Fifty-two food and eight clinical isolates of L. monocytogenes were obtained from France, Japan, and the United States. Their pathogenicity in nonimmunocompromised female ICR mice was determined by intraperitoneal (i.p.) injection of the mice with test strains at 10(8) to 10(9) CFU per mouse. Five mice were injected with each Listeria strain and observed for 5 days. Listeria isolates that caused at least one death in 5 days were considered pathogenic. Isolates that caused no deaths in 5 days were considered nonpathogenic. All strains except Listeria innocua and one L. monocytogenes serotype 4b strain (RM3-1) isolated from bovine raw milk were pathogenic to nonimmunocompromised mice. Three food isolates of L. monocytogenes serotype 1/2c were weakly pathogenic to nonimmunocompromised mice, killing a maximum of 50% of mice at 10(8) CFU. Strains with no pathogenicity or reduced pathogenicity were further tested for their pathogenicity to immunocompromised mice. Each strain was inoculated i.p. into five mice at 10(3) to 10(10) CFU per mouse. No deaths of immunocompromised mice inoculated with 10(8) CFU were observed, but 20 to 40% of the mice died when inoculated with 10(9) CFU of L. monocytogenes RM3-1. The three L. monocytogenes serotype 1/2c isolates were also weakly pathogenic to immunocompromised mice, with two of the three isolates killing < or = 60% of mice at doses of < or = 10(8) CFU. The hemolytic activity of the three weakly pathogenic serotype 1/2c isolates was similar to that of pathogenic strains. However, the nonpathogenic strain RM3-1 was not found to be hemolytic on horse blood agar. We have identified several L. monocytogenes strains with reduced virulence levels. Further characterization of such isolates may aid in understanding factors affecting the variation in virulence among strains.

Nonhuman primate model for Listeria monocytogenes-induced stillbirths.

Listeria monocytogenes, isolated from outbreaks in either human or nonhuman primate populations, was administered orally at doses ranging from 10(6) to 10(10) CFU. Four of 10 treated animals delivered stillborn infants. L. monocytogenes was isolated from fetal tissue, and the pathology was consistent with L. monocytogenes infection as the cause of pregnancy loss. For all pregnancies resulting in stillbirths, L. monocytogenes was isolated from maternal feces, indicating that L. monocytogenes had survived and had probably colonized the gastrointestinal tract. Antibodies and antigen-specific lymphocyte proliferation against Listeria increased in animals that had stillbirths.