High-flow nasal cannula oxygen therapy for respiratory management after postoperative re-intubation/re-extubation in patients with trisomy 18 and trisomy 13: Two case reports.

We present two cases of general anesthesia in children with 18, 13 trisomy. One patient had difficulty with intubation and had to be reintubated postoperatively, another developed postoperative acute respiratory distress syndrome. The use of postoperative high-flow nasal cannula oxygen therapy to avoid reintubation is considered a feasible strategy.

Biologically transparent illumination is a safe, fast, and simple technique for detecting the correct position of the nasogastric tube in surgical patients under general anesthesia.

The aim of this study was to evaluate the effectiveness of using biologically transparent illumination to detect the correct position of the nasogastric tube in surgical patients. This prospective observational study enrolled 102 patients undergoing general surgeries. In all cases, a nasogastric tube equipped with a biologically transparent illumination catheter was inserted after general anesthesia. The identification of biologically transparent light in the epigastric area either with or without finger pressure indicated that the tube had been successfully inserted into the stomach. X-ray examination was performed to ascertain the tube position and was compared with the findings of the biologically transparent illumination technique. Biologically transparent light was detected in 72 of the 102 patients. In all of these 72 patients, the position of the nasogastric tube in the stomach was confirmed by X-ray examination. The light was not detected in the other 30 patients; X-ray examination showed that the nasogastric tube was positioned in the stomach in 21 of these 30 patients but not in the other 9. The sensitivity and specificity of the illumination were 77.4% and 100%, respectively. The results suggest that biologically transparent illumination is a useful and safe technique for detecting the correct position of the nasogastric tube in surgical patients under general anesthesia. When the BT light cannot be identified, X-ray examination is mandatory to confirm the position of the nasogastric tube.

Management of pregnancy complicated by ankylosing spondylitis: A case report and literature review.

Pregnancy complicated by ankylosing spondylitis is rare. Labor assistance and instrumental delivery may be difficult due to hip stiffness. Restriction in lumbar flexion may cause difficulties in administering neuraxial analgesia. Difficult intubation for general anesthesia due to limited neck mobility is another potential risk that must be considered.

[Parenteral fluid therapy in the pediatric surgical patient].

Perioperative fluid therapy aims to provide water, electrolytes and calorie to maintain metabolic homeostasis. The landmark article in which Holliday and Segar proposed the rate and composition of parenteral maintenance fluids for hospitalized children is used to the fluid management for the pediatric surgical patient. Critically ill patients require meticulous intraoperative fluid management to avoid acidosis, hypoglycemia, hyponatremia, and hypocalcemia as well as to maintain adequate intravascular volume. The glucose, electrolyte, and intravascular volume requirements of the pediatric surgical patient may be quite different from the original population described, and consequently, use of traditional hypotonic fluids may cause complications, such as hyperglycemia and hyponatremia in the postoperative surgical patient. Routine intraoperative dextrose administration is no longer necessary. We should ultimately change our approach according to major intraoperative fluid shifts by rational, monitored, goal-directed combination of both crystalloid and colloid therapy, similar to that occurring in adult surgical patients.

Induction of nitric oxide production in RAW264.7 cells under serum-free conditions by O-antigen polysaccharide of lipopolysaccharide.

BACKGROUND: Lipopolysaccharide derived from Pantoea agglomerans (LPSp) mainly consists of two aggregates, the high-molecular aggregate (HMM-LPSp) and the low-molecular aggregate (LMM-LPSp). The structural differences between HMM-LPSp and LMM-LPSp seem to depend on the length of the O-antigen polysaccharide because the lipid A regions of the two fractions are quite similar. In this study, we examined the biological activity of LPSp focusing on the O-antigen polysaccharide using HMM-LPSp and LMM-LPSp under serum-free conditions. MATERIALS AND METHODS: The binding of LPSp to RAW264.7 cells under serum-free conditions was analyzed by flow cytometry using LPSp-conjugated fluorescein isothiocyanate (FITC-LPSp). The biological activities of HMM-LPSp and LMM-LPSp under serum-free conditions were evaluated by the nitric oxide production. RESULTS: FITC-LPSp showed higher fluorescence intensity under serum-free than serum-containing conditions. HMM-LPSp induced higher nitric oxide production than LMM-LPSp under serum-free conditions. CONCLUSION: The present study indicates that the reactivity of LPSp is affected by the O-antigen polysaccharide under serum-free conditions.

Biological response modifiers used in cancer biotherapy.

Biotherapy is a form of treatment that uses the natural immune system to protect the body against infection, cancer, and other diseases, and can fortify the body against some side-effects of other treatments. Biotherapy employs substances called biological response modifiers (BRMs), which include vaccines, monoclonal antibodies, cytokines, and adjuvants. BRMs are used alone or in combination with each other. Several BRMs are widely accepted in the treatment of certain types of cancer, while others are being tried in research studies. Side-effects of biotherapy vary among agents and patients. However, these side-effects usually disappear after the end of treatment.

The involvement of O-antigen polysaccharide in lipopolysaccharide in macrophage activation.

Bacterial lipopolysaccharide (LPS), which is generally considered to be an endotoxin, is the major constituent of the outer membrane of Gram-negative bacteria. The structure of LPS consists of three regions; lipid A, core oligosaccharide and O-antigen polysaccharide (O-PS). The structures of lipid A and core oligosaccharide are highly conserved among bacterial genera, but that of O-PS varies and differs in common bacterial species. Although studies of the biological activities of LPS have mainly focused on the lipid A moiety, a recent study gradually clarified the importance of O-PS to elicit the biological activities. In this review, we summarize previous studies on the correlation between the structure of O-PS and the biological activity of LPS, and discuss the possibility of innovative drug development using modified and synthetic LPS.

A mixture of Salacia oblonga extract and IP-PA1 reduces fasting plasma glucose (FPG) and low-density lipoprotein (LDL) cholesterol levels.

At present, lifestyle-related diseases are one of the most critical health issues worldwide. It has been reported that lipopolysaccharide derived from a Gram-negative bacteria (IP-PA1) symbiotic with wheat exhibited several advantageous biological effects, such as the reduction of plasma glucose levels in NOD mice and low-density lipoprotein (LDL) levels in WHHL rabbits. In this study, the beneficial effects on plasma glucose and lipids of a tea (SI tea) consisting of IP-PA1 and Salacia (which contains an inhibitor of α-glucosidase) were investigated in the KK-Ay/TaJcl type 2 diabetic model mice and in human subjects with premetabolic syndrome in a double-blind, randomized study. SI tea significantly decreased plasma glucose levels in KK-Ay/TaJcl mice. A clinical trial of SI tea was performed with 41 subjects between the ages of 40 and 69, who belonged either to a high plasma glucose group (HG: FPG 100-125 mg/dl) or to a hyperlipidemia group (HL: TG ≥ 150 mg/dl, or LDL ≥ 120 mg/dl, or HDL < 40 mg/dl). These subjects ingested either Salacia without IP-PA1 (the control) or SI tea. Blood samples were collected at 0, 30, and 60 days after initiating SI tea treatment, and were measured for FPG, HbA1c, TG, LDL, and HDL. These results showed that SI tea reduced FPG and HbA1c more rapidly than the control in the HL group, and also significantly improved LDL and HDL levels in the HG group. Thus, SI tea may be helpful in preventing lifestyle-related diseases.

The effect of altering skin-surface cooling speeds on vasoconstriction and shivering thresholds.

BACKGROUND: Both core and skin temperatures contribute to steady-state thermoregulatory control. Dynamic thermoregulatory responses trigger aggressive defenses against rapid thermal perturbations. These responses potentially complicate interpretation of thermoregulatory studies and could slow induction of therapeutic hypothermia. We thus tested the hypothesis that rapid external skin-cooling triggers vasoconstriction and shivering at higher mean skin temperatures than slow or moderate rates of skin cooling. METHODS: Eleven healthy volunteers were cooled at 3 skin-cooling rates using forced air or/and conductive cooling in random order. One day volunteers received slow (≈2°C/h) skin cooling, and on another day, they received both medium (≈4°C/h) and fast (≈6°C/h) skin cooling. An endovascular heat-exchanging catheter maintained core temperature. Fingertip blood flow ≤0.25 mL/min defined onset of vasoconstriction; sustained ≥25% increase in oxygen consumption defined onset of shivering. Results were evaluated with repeated-measures analysis of variance, with P < 0.05 representing statistical significance. RESULTS: Volunteers were 25 ± 5 years of age (mean ± SD), 175 ± 7 cm tall, and weighed 63 ± 10 kg. Core temperature remained constant (≈37°C) throughout each study day. At vasoconstriction, mean skin temperatures were 33.2°C (95% confidence interval [CI]: 32.0°C, 34.4°C), 33.5°C (95% CI: 32.3°C, 34.7°C), and 33.0°C (95% CI: 31.4°C, 34.6°C) at slow, medium, and fast skin-cooling rates, respectively. Mean skin temperatures at shivering were also comparable: 31.4°C (95% CI: 30.3°C, 32.5°C), 31.5°C (95% CI: 30.2°C, 32.8°C), and 30.7°C (95% CI: 28.9°C, 32.5°C), respectively. CONCLUSIONS: Onset of vasoconstriction and shivering occurred at similar mean skin temperatures with all 3 cooling rates. Aggressive surface cooling can thus be used in thermoregulatory studies and for induction of therapeutic hypothermia without provoking dynamic thermoregulatory defenses.

The effects of nefopam on the gain and maximum intensity of shivering in healthy volunteers.

BACKGROUND: Mild hypothermia has been shown to improve neurologic outcome after cardiac arrest. Nefopam, a centrally acting, nonsedative analgesic, decreases the threshold of shivering, but not vasoconstriction, and thus might be a suitable drug for induction of therapeutic hypothermia. However, not only the threshold but also the gain and maximum intensity of shivering define the thermoregulatory properties of a drug and thus are clinically important. Therefore, we evaluated the gain and maximum intensity of shivering at 2 different doses of nefopam and placebo. METHODS: Seven healthy volunteers were randomly assigned to 3 study days: (1) control (saline), (2) small-dose nefopam (50 ng/mL), and (3) large-dose nefopam (100 ng/mL). On all study days volunteers were cooled using central venous infusion of cold IV fluid while mean skin temperature was maintained at 31 degrees C. Core temperature was recorded at the tympanic membrane. Threshold, gain, and maximum intensity of shivering were evaluated using oxygen consumption. RESULTS: Both 50 and 100 ng/mL nefopam significantly reduced the shivering threshold as well as the gain of shivering: shivering threshold: 35.6 degrees C + or - 0.2 degrees C (control); 35.2 degrees C + or - 0.3 degrees C (small dose); 34.9 degrees C + or - 0.5 degrees C (large dose), P = 0.004; gain of shivering: 597 + or - 235 mL x min(-1) x degrees C(-1) (control); 438 + or - 178 mL x min(-1) x degrees C(-1) (small dose); 301 + or - 134 mL x min(-1) x degrees C(-1) (large dose), P = 0.028. Maximum intensity of shivering did not differ among the 3 treatments. CONCLUSIONS: Nefopam significantly reduced the gain of shivering. This reduction, in combination with a reduced shivering threshold, will allow clinicians to cool patients even further when therapeutic hypothermia is indicated.

Mechanism for maintaining homeostasis in the immune system of the intestine.

Every organism possesses a mechanism for maintaining homeostasis. We have focused on the immune system as a system that helps maintain homeostasis of the body, and particularly on the intestine as the largest organ of immunity in the body. We have also focused our research on the mechanism that responds to foreign substances in the intestine, especially the toll-like receptors (TLR). The activation of myeloid differentiation primary response gene 88 (MyD88) signal transduction as a response to TLR in the intestine is believed to contribute to the maintenance of homeostasis of the body through the homeostasis of the intestine. Furthermore, significant findings were reported in which signal transduction from TLR4 was essential for the maintenance and regulation of the intestine. These results strongly suggest the possibility that homeostasis in the intestine is maintained by TLR4, and signaling by TLR4 after exposure to lipopolysaccharide (LPS) probably has a role in regulating homeostasis. It is expected that the prevention and treatment of various diseases using TLR4 will continue to develop. As LPS is a substance that enhances the activity of TLR4, it will also attract attention as a valuable substance in its own right.

Intestinal macrophages involved in the homeostasis of the intestine have the potential for responding to LPS.

Recently, there has been interest in the tertiary functions of food, those that maintain human health. Moreover, lipopolysaccharides (LPS), which are components of Gram-negative bacteria, have been found to be highly effective in activating innate immunity and have been rediscovered as new functional food materials. In this review, we discuss the significance of LPS as a food component with reference to these tertiary functions based on recent findings. There is special emphasis on the plasticity of responses to LPS by intestinal macrophages. According to the macrophage-network theory, local macrophages cooperate with other tissue macrophages. For this reason, this review also discusses the possibility that information is transferred throughout the body from intestinal macrophages.

Utility and safety of LPS-based fermented flour extract as a macrophage activator.

The immune system is part of the homeostasis system. Our research is focused on ways to maintain health, with an emphasis on the role of macrophages. We have hypothesized that tissue macrophages form a systemic network which we believe contributes to the homeostasis system, and have named it the 'macrophage network.' This network creates a dynamic equilibrium situation where macrophages control homeostasis. Our research is based on this macrophage network theory as we believe that the innate immune system provides the foundation for the homeostasis system. As part of our research, we have demonstrated that macrophage activation can provide protection and therapeutic effects for various diseases. Therefore, we have also focused on lipopolysaccharide (LPS). We proved that the LPS of Pantoea agglomerans (which we have named IP-PA1) was useful in preventing various health disorders and in restoring health when administered via the oral or transdermal route. We also developed a 'fermented flour extract', which consists largely of IP-PA1. For LPS to become a valuable commodity, it is very important to provide assurance about safety (when administered orally or transdermally) to build confidence. For this reason, we tested fermented flour extract (in which the major component was IP-PA1) to confirm that it was safe. The results of these safety trials confirmed that oral and transdermal administration of fermented flour extract was very safe. Thus, we believe that fermented flour extract is a new substance that will have applications in health food, cosmetics, animal feeds, fisheries feeds and drugs industries.

Intracellular localization of CD14 protein in intestinal macrophages.

BACKGROUND: Our research is focused on intestinal macrophages, which are believed to contribute to the maintenance of intestinal homeostasis. In addition, intestinal macrophages are unique in that there is an impairment of expression of tumor necrosis factor (TNF) from lipopolysaccharide (LPS). This characteristic can be attributed to the lack or poor level of expression of toll-like receptor 4 (TLR4) or CD14 on the membrane of intestinal macrophages. We therefore decided to identify where CD14 was localized in intestinal macrophages. MATERIALS AND METHODS: The endoplasmic reticulum and Golgi apparatus were double stained and the intracellular localization in the intestinal macrophages was observed using a confocal laser microscope. RESULTS: CD14 of peritoneal macrophages was expressed both in the endoplasmic reticulum and Golgi apparatus. By contrast, intestinal macrophages expressed very little CD14 on the cellular membrane. CD14 was present in the endoplasmic reticulum of intestinal macrophages, but was rare in the Golgi apparatus. CONCLUSION: The lack of expression of CD14 on the cell membrane of intestinal macrophages may be caused by transport interference from the endoplasmic reticulum to the Golgi apparatus.

Thermodilution and esophageal Doppler ultrasound in the assessment of blood flow changes induced by endotoxin and dobutamine.

BACKGROUND: Intermittent (IT) and continuous (CT) thermodilution and esophageal Doppler (ED), are all used for hemodynamic monitoring. The aim of this study was to test the agreement between these methods during endotoxin (ET) and dobutamine infusion. METHODS: Twenty-two pigs (39 +/- 1.8 kg body weight) were randomized to general anesthesia and either continuous ET (n = 9) or placebo (PL, n = 13) infusion. After 18 hours of ET or PL infusion, the animals were further randomized to receive dobutamine (n = 3 in ET, n = 5 in PL) or PL. A set of measurements using the three methods were obtained every hour, and the relative blood flow changes between two subsequent measurements were calculated. RESULTS: Bias or limits of agreement for flows were 0.73 L/min or 1.80 L/min for IT and CT, -0.33 L/min or 4.29 L/min for IT and ED, and -1.06 or 3.94 for CT and ED (n = 515, each). For flow changes they were 1% or 44%, 2% or 59%, and 3% or 45%, respectively. Bias and limits of agreement did not differ in ET- and PL-treated animals or in animals with or without dobutamine. Despite significant correlation between any two methods, the respective correlation coefficients (r) were small (IT vs. CT: 0.452; IT vs. ED: 0.042; CT vs. ED: 0.069; all p < 0.001). The same directional changes were measured by any two methods in 49%, 40%, and 50%. When IT flows >5 L/min were compared with IT flows 5 L/min.

Development and potential use of a monoclonal antibody to the lipopolysaccharide of Pantoea agglomerans (IP-PA1).

BACKGROUND: The lipopolysaccharide of Pantoea agglomerans (IP-PA ) has been shown to be effective and safe in the prevention of various diseases, such as bacterial or viral infection, lifestyle-related diseases, when administered transdermally or orally. To clarify the mechanisms of the preventive or therapeutic effect induced by IP-PA1, we tried to establish a monoclonal antibody to detect IP-PA1. The enzyme-linked immunosorbent assay (ELISA) was used to measure the amount of IP-PA1. MATERIALS AND METHODS: Antibodies were raised by immunization using heat-killed Pantoea agglomerans and screening was conducted to isolate monoclonal antibodies specific to IP-PA1. RESULTS: Six kinds of IP-PA1 specific monoclonal antibodies with different epitopes were established. An ELISA using the monoclonal antibodies was successfully established which could specifically detect IP-PA1. CONCLUSION: By use of this ELISA, the staple food content and pharmacodynamic analysis of IP-PA1 could be conveniently estimated.

Treatments for the activating macrophages that reduces surgical stress and postoperative mortalities from bacterial infections and tumor metastases.

BACKGROUND: Some of the mortalities caused by infectious diseases and/or distant metastases following surgery are thought to be due to immunological suppression. For this reason, techniques that reduce immunological suppression following surgery may reduce mortalities and/or incidences of micrometastases in distant organs. MATERIALS AND METHODS: Mice were anesthetized and their peritoneal cavities were opened for 30 min. Immunological suppression was estimated by the presence of tumor necrosis factor-a (TNF) after injection with OK-432 (dead bacterial bodies). The mice were administered with either Staphylococcus aureus or cancer cells of Meth A fibrosarcoma. Survival times and lung metastastic foci were then observed at 3 weeks. Results were compared for mice with or without treatment by OK432 or TNF prior to surgery. RESULTS: While significant suppression of TNF production was observed after laparotomy, administration of a macrophage-activating agent (TNF or OK-432) 3 h prior to laparotomy prevented immune suppression after the laparotomy. Laparotomy increased mortalities from bacterial infections and promoted the number of lung metastases. By contrast, administration of TNF or OK-432 3 h prior to the laparotomy decreased mortalities and metastases after the laparotomy. CONCLUSION: These results suggest that appropriate activation of macrophages prior to surgery is a method to reduce some of the detrimental effects caused by surgical operations.

Cloning and characterization of a LPS-regulatory gene having an LPS binding domain in kuruma prawn Marsupenaeus japonicus.

LPS is known as an effective stimulator of the immune system in various animals, including mammals and horseshoe crabs (HSC). Both of these animal groups have suppressive regulatory proteins for the LPS response, e.g. the bactericidal/permeability increasing protein in mammals and anti-LPS factor (ALF) in HSC. Prawns are a valuable aquaculture species, but the regulatory molecules and/or mechanisms that respond to LPS are largely unknown. To investigate the molecular mechanism of the LPS response in kuruma prawns, we cloned a cDNA having a LPS binding domain. A full-length cDNA gene, denoted as M-ALF (Marsupenaeus japonicus ALF-like peptide) was cloned that consisted of 746bp and encoded 123 amino-acid residues. The 3' non-translated region of this gene had the pentamer of ATTTA repeated four times; this is known as sequences for messenger RNA stabilization. Deduced amino-acid sequences showed a 42% homology with Japanese HSC-ALF. In particular, both have clusters of basic and hydrophobic amino acids, indicating that the region is probably binding to lipid A. The mRNA expression was determined for hemocytes, lymphoid organs, hearts, intestines and gills by RT-PCR. The mRNA expression was augmented 1.5-3h after LPS administration in lymphoid organs, but then decreased to normal level at 6h. Synthetic peptides containing Cys30 to Cys51 had LPS neutralizing activity to the Limulus reaction and NO production in RAW264.7 cells. These data suggest that in kuruma prawns, M-ALF acts as a LPS regulator during the acute phase response after invasion of pathogens.