Effect of infusion time of intravenous acetaminophen on blood pressure in the intensive care unit.

OBJECTIVE: To understand the effect of prolonged intravenous acetaminophen infusion on blood pressure. MATERIALS AND METHODS: We retrospectively studied a cohort of intensive care patients receiving initial intravenous acetaminophen. We used propensity score matching to adjust for differences between patients who were classified into two groups: control (acetaminophen infusion for 15 minutes) and prolonged administration (acetaminophen infusion for > 15 minutes). RESULTS: After acetaminophen administration, diastolic blood pressure was unchanged in the control group, and was significantly lower at 30 and 60 minutes in the prolonged administration group. CONCLUSION: Prolonged duration of acetaminophen infusion did not prevent acetaminophen-induced blood pressure reduction.

Gastrointestinal IgG4 Deposition Is a New Histopathological Feature of Eosinophilic Gastroenteritis.

BACKGROUND: The pathogenesis of eosinophilic esophagitis involves immunoglobulin G4 (IgG4) deposition. However, the relationship between IgG4 and eosinophilic gastroenteritis (EGE) is unclear. AIMS: To investigate gastrointestinal deposition of IgG4 in EGE. METHODS: Biopsies of the esophagus, stomach, and small intestine were evaluated in patients with and without EGE. Immunohistochemical staining for IgG4 was performed, and the proportions of the stained areas were compared. Sera from patients with EGE were assayed for food-specific IgG4, including egg white, wheat, rice, soy, and cow milk. RESULTS: Seventeen patients were included in this study (EGE group, n = 10; control group, n = 7). Compared with the control group, the proportion of IgG4-stained area in the EGE group was approximately threefold higher (40.2% [32.3-49.5]) vs. 12.1% [4.0-21.9], p = 0.014) in the esophagus, fivefold higher in the stomach (17.3% [11.1-26.2] vs. 3.7% [1.5-5.2], p = 0.014), and sixfold higher in the small intestine (28.0% [15.0-33.2] vs. 4.5% [2.6-9.8], p = 0.019). There was no significant association between the proportion of IgG4-stained area and the number of infiltrating eosinophils. Serum egg white-specific IgG4 levels were correlated with the proportion of IgG4-stained areas in the small intestine (R = 0.7, p = 0.035). CONCLUSIONS: IgG4 accumulated within the gastrointestinal mucosa in EGE. The positive correlation between serum egg white-specific IgG4 levels and the proportion of IgG4-stained areas in the small intestine suggests a role for IgG4 in the disease pathophysiology.

Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice.

We determined the bone mineral density (BMD) and the expression of serum bone formation marker (procollagen type I N-terminal propeptide: PINP) and bone resorption marker (C-terminal telopeptide of collagen: CTX) by ELISA to evaluate ovariectomy-induced osteoporosis in ovariectomized (OVX) mice. The intestinal microbiota of the mice was assessed using 16S rRNA gene sequencing. OVX mice exhibited a lower BMD of 87% with higher serum levels of CTX and PINP compared to sham-operated (sham) mice. The cecum microbiome of OVX mice showed lower bacterial diversity than that of sham mice. TNFα mRNA levels in the colon were 1.6 times higher, and zonula occludens-1 mRNA and protein expression were lower in OVX mice than in sham mice, suggesting that ovariectomy induced inflammation and increased intestinal permeability. Next, we used antibiotic treatment followed by fecal microbiota transplantation (FMT) to remodel the gut microbiota in the OVX mice. A decrease in PINP was observed in antibiotic-treated mice, while there was no change in BMD or CTX between mice with and without antibiotic treatment. Oral transplantation of the luminal cecal content of OVX or sham mice to antibiotic-treated mice did not affect the BMD or PINP and CTX expression. Additionally, transplantation of the luminal contents of OVX or sham mice to antibiotic-treated OVX mice had similar effects on BMD, PINP, and CTX. In conclusion, although ovariectomy induces dysbiosis in the colon, the changes in the gut microbiota may only have a minor role in ovariectomy-induced osteoporosis.

NOD-Like Receptor Family Pyrin Domain-Containing 3 Inflammasome Activation Exacerbates 5-Fluorouracil-Induced Small Intestinal Mucositis via Interleukin-1ß Activation.

BACKGROUND AND AIM: 5-Fluorouracil (5-FU) is an anticancer agent that induces intestinal mucositis, which causes diarrhea and dehydration. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is responsible for inflammatory response activation via caspase-1 cleavage and subsequent interleukin-1ß (IL-1ß) and IL-18 activation and secretion. The objective of this study was to determine the role of the NLRP3 inflammasome in 5-FU-induced small intestinal mucositis. METHODS: Small intestinal mucositis was induced in wild-type, NLRP3-/-, and caspase-1-/- mice by intraperitoneal injection of 5-FU. Some mice received intraperitoneal injection of a caspase-1 inhibitor, recombinant IL-1ß or IL-18, or neutralizing antibody against IL-1ß. RESULTS: Mice treated with 5-FU developed small intestinal mucositis with diarrhea and body weight loss, characterized by a decrease in villus height and the villus height-to-crypt depth ratio. These histological changes peaked on day 3 and were accompanied by an increase in mRNA expression of NLRP3 and IL-1ß and protein expression of cleaved caspase-1 and mature IL-1ß. Mature IL-18 protein expression was not affected by 5-FU administration. NLRP3-/- mice exhibited less severe 5-FU-induced mucositis, and this phenotype was mimicked by genetic depletion or pharmacological inhibition of caspase-1. Small intestinal mucositis was aggravated by exogenous IL-1ß and neutralized by IL-1ß antibody treatment. Administration of exogenous IL-18 or anti-IL-18 antibody did not affect any parameters associated with mucositis. NLRP3, cleaved caspase-1, and IL-1ß were expressed by inflammatory cells (mainly macrophages) in the lamina propria and damaged epithelial cells. CONCLUSIONS: NLRP3 inflammasome activation may exacerbate 5-FU-induced small intestinal mucositis via IL-1ß maturation.

Utility of Kyoto Classification of Gastritis in subjects with a high-negative titer of anti-Helicobacter pylori antibody during a medical check-up.

Subjects with a high-negative titer (3-9.9 U/ml) of serum anti-Helicobacter pylori (H. pylori) antibody represent a heterogeneous group of currently H. pylori-infected, H. pylori-uninfected, and previously H. pylori-infected cases. We investigated the characteristics of subjects with a high-negative titer during a medical check-up and the utility of H. pylori infection score, the sum of scores of endoscopic findings based on the Kyoto Classification of Gastritis, for diagnosing H. pylori infection. Subjects with 13C-urea breath test-positive or H. pylori stool antigen test-positive were diagnosed as currently H. pylori-infected. Although around half of subjects with a high-negative titer were after eradication therapy (48.6%), currently H. pylori-infected were considerably confirmed (11.7%). H. pylori infection score showed a high value of area under the receiver operating characteristic curve [0.92; 95% confidence interval (CI), 0.84-1.00] with the most suitable cut-off value of 1.0 (sensitivity: 0.92; specificity: 0.90). Multivariate logistic regression analysis revealed that H. pylori infection score was an independent factor associated with increased prevalence of H. pylori infection (odds ratio, 9.53; 95% CI, 2.64-34.40; p<0.001). Currently H. pylori-infected subjects were considerably included among the subjects with a high-negative titer, and the Kyoto Classification of Gastritis was useful to predict current H. pylori infection.

Gastric acid inhibitor aggravates indomethacin-induced small intestinal injury via reducing Lactobacillus johnsonii.

Proton pump inhibitors (PPIs) alter the composition of the intestinal microbiome, exacerbating indomethacin (IND)-induced small intestinal damage. Vonoprazan fumarate inhibits gastric acid secretion using a different mechanism from PPIs. We investigated the effects of both drugs on the intestinal microbiome and IND-induced small intestinal damage. We sought to clarify whether PPI-induced dysbiosis and worsening of the damage were due to a specific drug class effect of PPIs. Rabeprazole administration increased operational taxonomic unit numbers in the small intestines of C57BL/6 J mice, whereas the difference was not significant in the vonoprazan-treated group but exhibited a trend. Permutational multivariate analysis of variance of the unweighted UniFrac distances showed significant differences between vehicle- and vonoprazan- or rabeprazole-treated groups. L. johnsonii was the predominant microbial species, and the population ratio decreased after vonoprazan and rabeprazole administration. The vonoprazan- and rabeprazole-treated groups showed increased IND-induced damage. This high sensitivity to IND-induced damage was evaluated by transplantation with contents from the small intestine of mice treated with either vonoprazan or rabeprazole. Supplementation of L. johnsonii orally in mice treated with rabeprazole and vonoprazan prevented the increase in IND-induced small intestinal damage. In conclusion, both rabeprazole and vonoprazan aggravated NSAID-induced small intestinal injury by reducing the population of L. johnsonii in the small intestine via suppressing gastric acid secretion.

[Targeted bacteremia surveillance throughout a year--comparison of community-acquired and hospital-acquired infection].

To keep an eye on severe nosocomial infection and to evaluate the clinical difference of blood-stream infection between community-acquired and hospital-acquired infection, a survey of blood culture was performed in National Tokyo Medical Center from the period between November 2000 and October 2001. There were 252 episodes detected in 219 patients (80 community-acquired episodes in 80 patients and 172 hospital-acquired episodes in 139 patients). The three most common foci of infection/pathogens were as follows: in the community-acquired cases; urinary tract, pneumonia, infective endocarditis/Escherichia coli, viridant group of streptococci, Streptococcus pneumoniae, and in the hospital-acquired cases; intra-venous catheter, urinary tract, neutropenia-related bacteremia/Staphylococcus aureus, coagulase negative Staphylococcus, Enterococcus. Fifteen patients with community-acquired bacteremia and 37 patients with hospital-acquired bacteremia had been died within a month of the episode; the mortality was not significantly different between the both. The average of peak serum concentrations of C-reactive protein during the episodes of community-acquired bacteremia was higher than that of hospital-acquired bacteremia. These findings probably show that life threatening bloodstream infections seemed to be more common in the community. The rate of nosocomial bacteremia was approximately 1%, and no outbreak was observed during the period. Targeted bacteremia surveillance is maybe useful and efficient method to detect severe hospital-acquired infections.