STUDY OBJECTIVE: To evaluate the effects of preanesthetic administration of intramuscular (IM) ranitidine on pH and volume of gastric contents in children. DESIGN: Three randomized treatment groups. SETTING: Central operating rooms at a university hospital. PATIENTS: Forty children age 1 to 10 years undergoing a variety of elective surgical procedures requiring general anesthesia with endotracheal intubation. INTERVENTIONS: IM ranitidine 1 mg/kg (n = 15) or 2 mg/kg (n = 15) was administered 2 hours prior to induction of anesthesia. Ten patients without ranitidine served as the control group. An orogastric tube was inserted into each patient. MEASUREMENTS AND MAIN RESULTS: Gastric fluid pH and volume were measured every hour in the three groups. Plasma ranitidine concentrations were measured in ten patients of the ranitidine-treated groups. The mean volume of gastric fluid at induction of anesthesia was significantly lower in the ranitidine-treated patients (2.4 ml for ranitidine 1 mg/kg, 3.2 ml for ranitidine 2 mg/kg) than in the controls (8.6 ml; p less than 0.05). The mean pH values at induction of anesthesia were significantly higher in the ranitidine-treated patients (4.6 for 1 mg/kg, 6.7 for 2 mg/kg) than in the controls (2.1; p less than 0.05). Dose-dependent plasma ranitidine concentrations were obtained. CONCLUSIONS: Preanesthetic IM ranitidine 1 to 2 mg/kg resulted in a higher pH and lower volume of gastric fluid at the time of induction and in a higher pH during 3 hours of anesthesia. This therapy may be a useful adjunct to premedication for children who have a greater than normal risk of pulmonary aspiration during anesthesia.

Child↗

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Expression of functional acetylcholine receptor from cloned cDNAs.

The cloned cDNAs encoding the four subunits of the Torpedo californica acetylcholine receptor, each carried by a simian virus 40 vector, direct the synthesis of the functional receptor in a combined expression system consisting of COS monkey cells and Xenopus oocytes. Our results suggest that all four subunits are required to elicit a normal nicotinic response to acetylcholine, whereas only the alpha-subunit is indispensable for alpha-bungarotoxin binding activity.

Animals↗

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Location of functional regions of acetylcholine receptor alpha-subunit by site-directed mutagenesis.

The availability of cloned cDNAs encoding the four subunits of the Torpedo acetylcholine receptor, which can be expressed to make functional receptors in Xenopus oocytes, has made possible a detailed investigation of the functions of the different structural components of the receptor. The functional analysis of receptors with alpha-subunits altered at specific sites by site-directed mutagenesis of the cDNA has allowed the location of specific regions of the alpha-subunit molecule involved in acetylcholine binding and forming a transmembrane ionic channel.

Animals↗

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Phosphodiesterase III inhibitor olprinone chlorate is not significantly removed by continuous venovenous hemodiafiltration.

The study objective was to determine whether a phosphodiesterase III inhibitor, olprinone chlorate, is effectively removed by continuous venovenous hemodiafiltration (CVVHDF) in a patient with cardiac and renal failure. The patient was a 73 year old man who had undergone coronary artery bypass grafting for ischemic heart disease and who developed cardiac and renal failure postoperatively. A 0.2 microg/kg per minute dosage of olprinone chlorate was administered intravenously for 120 minutes while the patient was treated with CVVHDF. Samples from the arterial and venous blood catheters and those from the ultradiafiltrate for 12 hours were collected to calculate pharmacokinetic parameters and clearance of hemodiafiltration. The calculated parameters were as follows: half-life of elimination phase: 4.96 hours; total clearance 3.40 ml/min per kg. The clearance of CVVHDF was 0.33 ml/min per kg. The olprinone chlorate clearance of CVVHDF approximates only 10% of total clearance in this case. CVVHDF may not produce significant reduction in the serum olprinone chlorate level. It is recommended that the infusion dosage of olprinone chlorate should be reduced when given to patients with renal failure even if treated with CVVHDF.

Aged↗

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Predictors of mortality in patients treated with continuous hemodiafiltration for acute renal failure in an intensive care setting.

We performed this study to identify predictors of mortality in critically ill patients treated with continuous venovenous hemodiafiltration (CVVHDF) for acute renal failure in an intensive care setting. It was an uncontrolled, observational study that took place in a general intensive care unit in a university hospital. Forty-one patients undergoing CVVHDF for acute renal failure in a consecutive sample of 1,018 ICU treatments were studied. The underlying disease included 25 postsurgical cases and 16 medical cases. Between survivors (n = 23) and nonsurvivors (n = 18), the following factors were assessed: demographic data; the number and type of failed organs; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; urine production; pH; base excess; serum creatinine levels; bilirubin levels; lactate levels; platelet counts; and hemodynamic variables, including cardiac index and central venous pressure. On univariate analyses, the number of failed organs (p < 0.01), presence of hepatic failure (p < 0.01), APACHE II scores (p < 0.01), pH (p < 0.01), base excess (p < 0.001), average urinary production before the initiation of CVVHDF (p < 0.05), and serum bilirubin (p < 0.01) and lactate levels (p < 0.001) were significantly different. Multiple regression analysis identified serum bilirubin (p < 0.01) and lactate levels (p < 0.01) as the predictors of hospital mortality. Presence of hepatic failure was also predictive of hospital mortality (p < 0.01) in the analysis of the type of organ failure. The cut-off value set at bilirubin levels > 10 mg/dl or arterial lactate levels > 3.5 mmol/L provided 83.3% sensitivity and 90.9% specificity in the prediction of hospital death. The crucial factors in predicting outcome of critically ill patients undergoing CVVHDF for renal failure are elevated serum bilirubin and lactate levels at the onset of CVVHDF. Presence of hepatic failure, defined as both jaundice and coagulopathy, may also worsen outcome of critically ill patients undergoing CVVHDF for renal failure. The cut-off value set at bilirubin levels > 10 mg/dl or arterial lactate levels > 3.5 mmol/L may serve as beneficial predictors of hospital mortality.

APACHE↗

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Mechanisms of cerebral protection by pentobarbital and nizofenone correlated with the course of local cerebral blood flow changes.

The effects of delayed administration of pentobarbital and a novel imidazole derivative (Nizofenone or Y-9179) on the infarction size following the regional cerebral ischemia were studied using the permanent middle cerebral artery (MCA) occlusion model in cats. The courses of local cerebral blood flow (lCBF) before and after drug administration were also studied using the hydrogen clearance method. The extent of infarction one week after MCA occlusion was significantly smaller in the drug-treated groups than in the control group. Regarding the time-course of lCBF, there was no significant differences between the control and the Y-9179 groups. On the other hand, pentobarbital administration caused a significant lCBF increase in low-flow areas where the lCBF following MCA occlusion was below 40 ml/100g/min. In spite of this flow increase, the corresponding cortical areas underwent infarction. Histological examination of the state of vasogenic edema revealed that the perivascular exudation of plasma fluid in the infarcted area was definitely less in the Y-9179 treated group than in the other groups. Results indicate that redistribution of lCBF may not be involved in the mechanism of cerebral protection by pentobarbital or Y-9179.

Animals↗

PubMedDate not supplied

Cellular changes induced in rats lungs by inhalation of ceramic fibres.

Explore the source record for details and available documents.

Administration, Inhalation↗

PubMedDate not supplied

Establishment of fluorescein diacetate and ethidium bromide (FDAEB) assay for quality assessment of isolated islets.

One of the most important factors in clinical islet transplantation is isolation of a great number of islets with good viability. According to viability assessments of isolated islets, the static incubation test and the perifusion test of islets, which are used retrospectively, take much time and need various apparatus. But viability assessments of isolated islets for clinical islet transplantation require a simple, rapid, sensitive, and prospective method. We have developed a microfluorometric viability assay for isolated human, porcine, and dog islets of pancreata using fluorescein diacetate and ethidium bromide (FDAEB). Fluorescein diacetate (FDA) causes live cells to fluoresce green under blue light excitation (490 nm) and ethidium bromide (EB) causes dead cells to fluoresce red. In this study, we investigated the applicability of FDAEB staining to quality assessment of isolated islets for clinical use by correlation with the counting method with insulin secretion of islets. Discrimination of living from dead islets by insulin secretion correlated well with viability as determined by FDAEB staining. The proportion of living islets within isolated canine islets, as measured by microfluorometric counting, was found to correlate highly significantly on low-temperature (24 degrees C) culture (R = 0.831, p < 0.001) and on 37 degrees C culture (R = 0.553, p < 0.05) with the insulin contents of the same islets. Therefore, it is possible to differentiate degrees of viability, and a scoring system is described for this purpose. The FDAEB assay prospectively and easily provides a rapid, accurate, and objective measurement of the proportion of living cells and dead cells in isolated islets for clinical islet transplantation.

Animals↗

PubMedDate not supplied

Functional expression of Fas and Fas ligand on human colonic intraepithelial T lymphocytes.

The expression of Fas, a cell surface receptor directly responsible for triggering cell death by apoptosis, and its ligand (FasL) was investigated on both human colonic intraepithelial T lymphocytes (IELs) and peripheral blood mononuclear lymphocytes (PBMLs). FACS analysis indicated that IELs have increased expression of Fas compared with PBMLs, together with the progress activation marker, CD45RO. A discrete fraction of freshly isolated IELs also constitutively expressed FasL, perhaps as a result of recent in vivo activation. Using monoclonal antibody APO2.7, which detects mitochondrial 7A6 antigen specifically expressed by cells undergoing apoptosis, we further investigated the apoptosis-inducing effect of anti-Fas monoclonal antibody (CH11) on both IELs and PBMLs. FACS analysis revealed that CH11 increased the percentage of apoptotic cells, in IELs but not in PBMLs. Culture with anti-FasL monoclonal antibody (4H9) significantly recovered cell viability in IELs, but not in PBMLs. These results indicate that IELs constitutively express both Fas and FasL and that Fas crosslinking generates signals resulting in apoptosis, outlining a potential mechanism involved in intestinal tolerance.

Adult↗

PubMedDate not supplied

Autologous serum deprivation restored IL-1 receptor antagonist production by peripheral blood mononuclear cells in patients with gastric cancer.

It has been established that cancer patients have immunosuppressive substances in their sera that depress cellular immunity. Although plasma exchanges have been attempted to remove these substances and to improve immunity to cancer, little is known about its mechanism from the viewpoint of cytokine pattern. The levels of the cytokines, tumour necrosis factor-alpha, interleukin 1beta, interleukin 6, interferon-gamma and interleukin-1 receptor antagonist (IL-1ra) by peripheral blood mononuclear cells (PBMC) were determined simultaneously by the whole-blood assay and the PBMC assay in 20 patients with gastric cancer and in 10 healthy volunteers. In both assays the cytokine levels were lower in patients with cancer compared with healthy controls, with the exception of IL-1ra. In the PBMC assay, the IL-1ra level in cancer patients was significantly higher than that in controls. No statistical correlation between the cytokine levels determined by the two assays was found. We suggest that autologous serum deprivation restored and enhanced IL-1ra production, and normalized the cytokine cascade in immune response, in patients with gastric cancer.

Adult↗

PubMedDate not supplied

Donor dendritic cells and recipient Kupffer cells in the induction of donor-specific immune hyporesponsiveness.

The aim of this study was to investigate the ability of portovenously administered donor antigens to induce immune hyporesponsiveness. Lewis (LEW, RT-1l) rats received Brown Norway (BN, RT-1n) rat donor splenocytes, via either the portal vein (PV group) or the peripheral vein (IV group). The immune responses of LEW rats, treated with either donor BN or third party Wistar King A (WKA, RT-1k) splenocytes were established by the persistence of donor dendritic cells (DCs) in the host liver measured using fluorescence microscopy and flow cytometry and by the mixed lymphocyte reaction (MLR). The effect of intravenous gadolinium chloride (GDCl3) on the blockade of Kupffer cell function prior to portovenous administration of splenocytes was also assessed. The MLR response was strongly inhibited in a BN-restricted manner after portovenous administration of donor BN splenocytes, but not by venous nor by portovenous administration of WKA splenocytes. Immunosuppression was blocked by pretreatment with GDCl3. The percentage of donor DCs in hepatic non-parenchymal cells (NPCs) was significantly higher in the PV group compared with the IV group. Treatment with GDCl3 decreased the percentage of donor DCs. In addition, cytotoxic T lymphocyte antigen 4 (CTLA4/CD152), which may function as an immune attenuator, was strongly stained, and B7 was weakly stained in recipient liver in the PV group compared with the IV group. These results suggest that both donor DCs and recipient Kupffer cells (self DCs) are involved in the induction of immune hyporesponsiveness by donor cells. This occurs via portovenous administration, in which a signal of the CTLA4-B7 pathway played an important part in inhibiting the interaction of CD28 and its B7 ligands.

Abatacept↗

PubMedDate not supplied

Bacterial lipopolysaccharide induces transforming growth factor beta and hepatocyte growth factor through toll-like receptor 2 in cultured human colon cancer cells.

This study examined, in human cancer lines, the pattern of cytokine production stimulated by lipopolysaccharide (LPS), a major component of outer surface of gram-negative bacteria, and characterized the expression pattern of CD14, cell surface LPS receptor antigen, and toll-like receptors (TLRs), which appear to be key regulators of the innate immune response system. Two colon cancer cell lines (DLD and LoVo), a hepatocellular carcinoma cell line and a myelomonocytic cell line were incubated with LPS for 0-72 h, and transforming growth factor (TGF) beta1 and beta2, hepatocyte growth factor (HGF) and interleukins 6, 8 and 15 were assayed. The only changes induced by incubation with LPS were significant increases in TGFbeta1 production at 12 h, and in HGF production at 72 h, in LPS-stimulated DLD cells, and significant increases in TGFbeta2 production after 12 h and in HGF after 72 h in LoVo cells. Using reverse transcriptase-polymerase chain reaction analysis, expression of CD14 and TLR-2 mRNA was detected in DLD and LoVo cells, and expression of TLR-4 mRNA was detected in PLC/PRF/5 and KG-1 cells. These results suggest that LPS induces TGFbeta and HGF production mediated by CD14/TLR-2 in cultured human colon cancer cell lines.

Antigens, CD↗

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Differential cytokine response in host defence mechanisms triggered by gram-negative and gram-positive bacteria, and the roles of gabexate mesilate, a synthetic protease inhibitor.

Bacterial infection results in the production of inflammatory mediators and may be involved in the pathogenesis of sepsis and/or systemic inflammatory response syndrome. The effect of lipopolysaccharide (LPS), a major component of the outer surface of Gram-negative bacteria, and Staphylococcal enterotoxin B (SEB), a superantigen of Gram-positive bacteria, on cytokine production in peripheral blood mononuclear cells (PBMCs) was examined. LPS significantly increased the production of proinflammatory and anti-inflammatory cytokines, and SEB enhanced the production of helper T lymphocyte type cytokines. These results illustrated the different responses to Gram-negative and Gram-positive bacterial infections. The effect of gabexate mesilate, a synthetic protease inhibitor, on cytokine production and expression of the toll-like receptor (TLR) was also examined. The results suggest that gabexate mesilate-induced inhibition of tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18) production in LPS-stimulated PBMCs is due to the inhibition of the nuclear factor-kappa B activation pathway and/or inhibition of the processing pathway of pro-TNF-alpha and pro-IL-18, not to down-regulation of TLR-2 or TLR-4.

Antigens, CD↗