Postoperative coagulopathy after liver resection--implications for epidural analgesia.
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Adult↗
Biomedical subjects
H J Lim
Publications and source records attributed to H J Lim.
Effects of isoflurane and propofol on cortical somatosensory evoked potentials during comparable depth of anaesthesia as guided by bispectral index.
BACKGROUND: The aim of this study was to determine if propofol caused less suppression of cortical somatosensory evoked potentials (SSEPs) during spine surgery compared with isoflurane during comparable depth of anaesthesia as guided by bispectral index (BIS) measurements. METHODS: This was a randomized controlled trial of propofol and isoflurane involving 60 patients undergoing elective spine surgery. BIS monitoring was used to guide a consistent and comparable depth of anaesthesia, the index was maintained at between 40 and 50 during anaesthesia. The cortical SSEP P40-N50 peak-to-peak amplitude and latency time to the P40 peak were measured before induction of anaesthesia, after induction of anaesthesia, at the start of skin incision, at the start of pedicle screw insertion and at the start of rod insertion, by a neurophysiologist blinded to drug allocation. RESULTS: Both propofol and isoflurane decreased SSEP amplitude and increased latency during the course of anaesthesia. After achieving a comparable depth of anaesthesia, the SSEP amplitude was significantly lower with isoflurane, 1.5 (1.0) vs 2.4 (1.4) muV (P=0.005). Latency was significantly longer with isoflurane, 39.5 (3.9) vs 37.3 (3.1) ms (P=0.024). Isoflurane was associated with greater variability of SSEP amplitude during the course of anaesthesia and surgery, coefficient of variation 35.4 (18.0) vs 21.2 (10.2)% (P=0.008). CONCLUSIONS: Propofol anaesthesia caused less suppression of the cortical SSEP, with better preservation of SSEP amplitude, and less variability at an equivalent depth of anaesthesia.
Adolescent↗
Organic and elemental carbon measurements during ACE-Asia suggest a longer atmospheric lifetime for elemental carbon.
During the ACE-Asia intensive field campaign (March 14-April 20, 2001), PM1.0 organic (OC) and elemental carbon (EC) concentrations were measured onboard the NOAA R/V Ronald H. Brown over the Northwest Pacific Ocean using a semi-continuous automated carbon analyzer downstream of a carbon-impregnated filter denuder. This OC and EC measurement achieved a mean time resolution of about 200 min over the Pacific Ocean, substantially lower than that achieved previously (24 h). The semi-continuous measurements, in which the adsorption artifact was substantially reduced using the denuder, showed good agreement with integrated artifact-corrected measurements made without a denuder. Mean particulate OC and EC concentrations were 0.21 and 0.09, 0.70 and 0.29, 1.00 and 0.27, and 2.43 and 0.66 microg of C m(-3) over the background Pacific Ocean, Asian-influenced Pacific Ocean, offshore of Japan, and Sea of Japan, respectively. On April 11, 90-min average OC and EC concentrations peaked at 4.0 and 1.3 microg of C m(-3), respectively, offshore of Korea over the Sea of Japan. The OC/EC ratio of 3.7 over the Sea of Japan and offshore of Japan was substantially higher than that of 2.5 over the Asian-influenced Pacific Ocean, even though backward air mass trajectories put the "Asian-influenced Pacific Ocean" sample downwind. The OC/EC ratio decreased with increasing time since the air mass encountered the source regions of China, Japan, and Korea. This suggests a longer atmospheric residence time for EC than for OC.
Aerosols↗
ACE-Asia intercomparison of a thermal-optical method for the determination of particle-phase organic and elemental carbon.
A laboratory intercomparison of organic carbon (OC) and elemental carbon (EC) measurements of atmospheric particulate matter samples collected on quartz filters was conducted among eight participants of the ACE-Asia field experiment The intercomparison took place in two stages: the first round of the intercomparison was conducted when filter samples collected during the ACE-Asia experiment were being analyzed for OC and EC, and the second round was conducted after the ACE-Asia experiment and included selected samples from the ACE-Asia experiment Each participant operated ECOC analyzers from the same manufacturer and utilized the same analysis protocol for their measurements. The precision of OC measurements of quartz fiber filters was a function of the filter's carbon loading but was found to be in the range of 4-13% for OC loadings of 1.0-25 microg of C cm(-2). For measurements of EC, the precision was found to be in the range of 6-21% for EC loadings in the range of 0.7-8.4 microg of C cm(-2). It was demonstrated for three ambient samples, four source samples, and three complex mixtures of organic compounds that the relative amount of total evolved carbon allocated as OC and EC (i.e., the ECOC split) is sensitive to the temperature program used for analysis, and the magnitude of the sensitivity is dependent on the types of aerosol particles collected. The fraction of elemental carbon measured in wood smoke and an extract of organic compounds from a wood smoke sample were sensitive to the temperature program used for the ECOC analysis. The ECOC split for the three ambient samples and a coal fly ash sample showed moderate sensitivity to temperature program, while a carbon black sample and a sample of secondary organic aerosol were measured to have the same split of OC and EC with all temperature programs that were examined.
Carbon↗
Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro.
Leptin, the product of ob gene, is an endocrine hormone that regulates adipose tissue mass. Recently, leptin has been found to generate a growth signal involving a tyrosine kinase-dependent intracellular pathway and promote angiogenic processes via activation of leptin receptor (Ob-R) in endothelial cells. However, it is not clear how leptin functions to promote multi-step processes involved in the neovascularization at the atherosclerotic plaque. We have examined the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and Ob-R in human atherosclerotic lesions, leptin-mediated angiogenesis in vivo and in vitro. Immunohistochemical analysis of human atherosclerotic aorta revealed an increased expression of Ob-R in the intima of neorevascularized regions and of both MMPs and TIMPs predominantly in the endothelial lining of intimal neovessels and macrophages/foam cells. In the rat corneal angiogenesis assay, leptin elicited a comparable sensitivity of angiogenic activity to those of vascular endothelial growth factor (VEGF). The immunohistological analysis of the leptin-treated rat cornea showed definitive rises in Ob-R, MMPs and TIMPs expression as well as those of VEGF receptor (VEGFR-1). Leptin (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells (HUVECs) and elevation of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression in a dose-dependent manner. Leptin also induced increases of MMP-2, MMP-9, TIMP-1, and Up-regulated the human coronary artery smooth muscle cells (HCASMCs). These findings suggest that leptin, a hormone with pluralistic properties including a mitogenic activity on vascular endothelial cells, plays a role in matrix remodeling by regulating the expression of MMPs and TIMPs. Taken together, our findings further provide evidences for leptin's role as an angiogenesis inducer in the normal organ (rat cornea) and in aberrant vasculature under duress like atherosclerosis.
Animals↗
A novel recombinant basic fibroblast growth factor and its secretion.
Basic fibroblast growth factor (FGF-2) is a pleiotropic mitogen which plays an important role in cell growth, differentiation, migration, and survival in different cells and organ systems. Recently, several clinical applications for FGF-2 gene transfer are being evaluated in wound healing and collateral artery development to relieve myocardial and peripheral ischemia due to the ability of FGF-2 to regulate the growth and function of vascular cells. However, FGF-2 lacks a classical hydrophobic secretion signal peptide, the FGF-2 chimeras containing various signal sequences have been explored. In this study, a novel recombinant 4sFGF-2 was constructed by replacing nine residues from the amino-terminus of native FGF-2 (Met1 to Leu9) with eight amino acid residues of signal peptide of FGF-4 (Met1 to Ala8) to better increase the secretion level of FGF-2. When the recombinant FGF-2 gene, cloned into the expression vector with CMV promoter, was expressed in COS-7 cells, the recombinant 4sFGF-2 was highly secreted into the media. The secreted 4sFGF-2 showed the same biological activity as the native FGF-2 in the dose-response effects on DNA synthesis and cell growth of rat aortic smooth muscle cells (RASMCs) and NIH3T3 cells. The 4sFGF-2 also was able to activate MAPK as wild FGF-2 in RASMCs. These results indicate that a novel recombinant 4sFGF-2 may be useful as clinical applicability of angiogenic growth factor gene transfer.
3T3 Cells↗
Role of drug release and liposome-mediated drug delivery in governing the therapeutic activity of liposomal mitoxantrone used to treat human A431 and LS180 solid tumors.
A previous study suggested that drug release is the dominating factor controlling biological activity of liposomal mitoxantrone in tissues where the rate of liposome accumulation is rapid. The studies described here attempted to address the question: under conditions where the rate of liposome accumulation is slow, does drug release or liposome-mediated drug delivery become the dominant factor controlling therapeutic activity? Liposomal mitoxantrone formulations exhibiting different drug-release characteristics were injected i.v. in mice bearing human carcinoma xenografts: A431 human squamous cell carcinoma and LS180 human colon cell carcinoma in SCID/RAG 2 mice. When lipid and drug levels were measured in established (>100-mg) tumors, accumulation was more rapid in the LS180 tumors (C(max) 4 h) than in the A431 tumors (C(max) 48 h). Mean area under the curve values for mitoxantrone measured over a 96-h time course in A431 tumors were 505, 304, and 93 microg. g(-1). h(-1) for 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol (Chol), 1, 2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/Chol, and free mitoxantrone, respectively. When a similar analysis was completed in LS180 tumors, the area under the curve values were 999, 749, and 251 microg. g(-1). h(-1) for DSPC/Chol, DMPC/Chol, and free mitoxantrone, respectively. Although drug delivery was less after administration of the DMPC/Chol liposomal mitoxantrone compared with the DSPC/Chol formulation, LS180 solid-tumor growth curves showed the treatment with the DMPC/Chol formulation produced greater delays in tumor growth compared with animals treated with the DSPC/Chol formulation. These data emphasize the importance of designing liposomal formulations that release drug after localization within a region of tumor growth.
Animals↗
Kupffer cells do not play a role in governing the efficacy of liposomal mitoxantrone used to treat a tumor model designed to assess drug delivery to liver.
A tumor model designed to assess liposome-mediated drug delivery to liver has been used in an attempt to better understand the mechanism of activity of liposomal mitoxantrone, a liposomal anticancer drug formulation that appears to be uniquely effective in treating this tumor model. Reductions in liposomal mitoxantrone accumulation in the liver were achieved either by use of poly(ethylene)glycol (PEG)-modified lipids or by methods designed to deplete liver phagocytes, a method referred to as hepatic mononuclear phagocytic system (MPS) blockade. A 2-fold reduction in mitoxantrone delivery to the liver was obtained using a mitoxantrone formulation with PEG-modified lipids, and a 3-fold reduction was obtained when liposomal mitoxantrone was given to animals pretreated to induce hepatic MPS blockade. Results demonstrate that the liposomal mitoxantrone formulation prepared with PEG-modified lipids was significantly less active than the formulations that did not contain PEG lipids, with median survival times of 17 days and 100% 60-day survival, respectively. In contrast, hepatic MPS blockade had no effect on the therapeutic activity of 1,2-dimyristoyl phosphatidylcholine/cholesterol (DMPC/Chol) mitoxantrone (100% 60-day survival). These data suggest that the hepatic MPS does not play a role in mediating the therapeutic activity of DMPC/Chol mitoxantrone in the treatment of liver localized disease. Results with formulations prepared with a PEG-stabilized surface, however, suggest that nonspecific methods to decrease liposome cell interactions inhibit the therapeutic activity of DMPC/Chol mitoxantrone.
Animals↗
Comparison of rocuronium and vecuronium pretreatment for prevention of fasciculations, myalgia and biochemical changes following succinylcholine administration.
BACKGROUND: The purpose of this study was to assess the effect of rocuronium pretreatment on the succinylcholine-induced fasciculations, myalgia and biochemical changes, and to compare it with vecuronium pretreatment. METHODS: We have studied 60 female patients undergoing minor elective surgery, in a prospective double blinded method. Three groups of 20 patients each was pretreated with either saline (control group), rocuronium 0.05 mg/kg (rocuronium group) or vecuronium 0.007 mg/kg (vecuronium group). Three min after the pretreatment, 1.5 mg/kg succinylcholine was injected. Single twitch responses to electrical stimulation were measured. Serum potassium and creatine kinase were respectively measured 5 min after succinylcholine and 24 h after operation. Fasciculations and myalgia on postoperative day 1 and day 2 were evaluated. RESULTS: The incidence of fasciculations was lowest in the rocuronium group, followed by the vecuronium group, and was highest in the control group. The incidence of myalgia on postoperative day 1 was lower in the rocuronium and vecuronium groups than the control group. The increase of serum creatine kinase was similar among the three groups, but there was no increase in serum potassium concentration in any group. No differences of the single twitch responses to electrical stimulation were found between the rocuronium and vecuronium groups. CONCLUSIONS: Rocuronium pretreatment was more effective in reducing fasciculations than was vecuronium pretreatment, but both were equally effective in preventing myalgia on postoperative day 1. This difference may reflect the differential activities of rocuronium and vecuronium at the neuromuscular junction. The increase of creatine kinase was not attenuated by any regimen.
Adult↗
Comparison of different hydrophobic anchors conjugated to poly(ethylene glycol): effects on the pharmacokinetics of liposomal vincristine.
Poly(ethylene glycol) (PEG) conjugated lipids have been used to increase the circulation longevity of liposomal carriers encapsulating therapeutic compounds. PEG is typically conjugated to distearoylphosphatidylethanolamine (DSPE) via a carbamate linkage that results in a net negative charge on the phosphate moiety at physiological pH. It was anticipated that the presence of this negative charge could have deleterious effects on liposome pharmacokinetic characteristics. We describe here the synthesis of a new class of neutrally charged PEG-lipid conjugates in which the PEG moiety was linked to ceramide (CER). These PEG-CER conjugates were compared with PEG-DSPE conjugates for their effects on the pharmacokinetics of liposomal vincristine. PEG-CER (78% palmitic acid, C16) and PEG-DSPE achieved comparable increases in the circulation lifetimes of sphingomyelin/cholesterol (SM/chol) liposomes. However, PEG-DSPE significantly increased the in vitro and in vivo leakage rates of vincristine from SM/chol-based liposomes compared to vincristine leakage observed when PEG-CER was used. The increase in drug leakage observed in vitro that was due to the presence of PEG-DSPE was likely due to the presence of a negative surface charge. Analysis of the electrophoretic mobilities of these formulations suggested that the negative surface charges were shielded by approx. 80% by the PEG layer extending from the membrane surface. In contrast, formulations containing PEG-CER had no surface charge and no electrophoretic mobility. A comparison of the effects of the ceramide acyl chain length (C8 through C24) on the pharmacokinetics of SM/chol/PEG-CER formulations of vincristine demonstrated that longer acyl chains on the PEG-CER were associated with longer circulation lifetimes of the liposomal carriers and, consequently, higher plasma vincristine concentrations. These data suggest that the short chain PEG-ceramides underwent rapid partitioning from the vesicles after i.v. administration, whereas the longer chain PEG-ceramides had stronger anchoring properties in the liposome bilayers and partitioned slowly from the administered vesicles. These data demonstrate the utility of ceramide-based steric stabilizing lipids as well as the potential for developing controlled release formulations by manipulating the retention of the PEG-ceramide conjugate in liposome bilayers.
Animals↗
Airway fire during elective tracheostomy.
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Adult↗
Influence of drug release characteristics on the therapeutic activity of liposomal mitoxantrone.
The influence of liposome drug release on the therapeutic activity of encapsulated mitoxantrone was investigated. Liposomes prepared from 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol (Chol) (55:45, molar ratio) or 1,2 dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/Chol (55:45, molar ratio) were loaded with mitoxantrone using the transmembrane pH gradient loading procedure. In vivo studies demonstrated that DMPC/Chol liposomes released drug faster (1.7 microg drug/microg lipid/hr) than did DSPC/Chol liposomes (<0.025 microg drug/microg lipid/hr). In BDF1 mice, the acute toxicities of DMPC/Chol and DSPC/Chol liposomal mitoxantrone were similar, with a maximum tolerated dose of approximately 30 mg drug/kg, in comparison with the maximum tolerated dose of free drug, which was approximately 10 mg/kg. Efficacy studies were conducted in BDF1 mice inoculated i.v. with murine P388 cells or L1210 tumor cells. These cells seed in the liver and spleen of animals after i.v. inoculation, and a single dose of DMPC/Chol liposomal mitoxantrone of 10 mg drug/kg resulted in 100% of the treated animals surviving for >60 days. In contrast, no long-term survivors were obtained in any other treatment group, even when drug doses were escalated to the maximum tolerated dose. Pharmacodynamic studies with DMPC/Chol liposomal mitoxantrone and DSPC/Chol liposomal mitoxantrone illustrate the importance of achieving a balance between drug release characteristics and drug delivery to the site of tumor progression.
Animals↗
Comparison of natural ostiotomy and antibiotic therapy in the treatment of acute maxillary sinusitis in rabbits.
The goal of this study was to compare natural ostiotomy and the administration of a systemic antibiotic in the treatment of acute maxillary sinusitis. Maxillary sinusitis was induced in 28 rabbits by blocking the natural ostium with a bone chip and by introducing 0.2 ml of a suspension of Streptococcus pneumoniae (2 x 10(9) cells/ml). The animals were divided into natural ostiotomy and antibiotic therapy groups: the natural ostiotomy group comprised 14 rabbits, in which the bone chip that blocked the natural ostium was removed; and the antibiotic therapy group comprised 14 rabbits treated with systemic antibiotic without reopening the ostium. The sinus mucosa of each group was examined histopathologically 2 weeks and 4 weeks after treatment. There were no significant differences in light microscopic findings between the natural ostiotomy and antibiotic therapy groups. Natural ostiotomy was as effective against acute maxillary sinusitis as the systemic administration of antibiotics. The results of this study suggest that natural ostiotomy and antibiotic therapy may be equally effective in the treatment of acute maxillary sinusitis in rabbits.
Acute Disease↗
Combined epidural analgesia and general anesthesia induce ischemia distal to a severe coronary artery stenosis in swine.
Epidural analgesia combined with general anesthesia may improve cardiac function and reduce the work of the heart by decreasing the rate pressure product. However, the effect of this combined technique has not been studied in the presence of severe coronary artery stenosis. Therefore, we investigated epidural analgesia combined with general anesthesia in a swine model with a tight coronary artery stenosis. The coronary stenosis placed around the proximal left anterior descending coronary artery (LAD) allowed normal blood flow at rest but only minimum hyperemia in response to the coronary dilator, adenosine. To accomplish an extensive sympathetic block, we injected enough bupivacaine 0.5% into the lumbar epidural space to reach at least the level of the first thoracic vertebra (T1). Epidural catheter position was verified by fluoroscopy. Hemodynamic changes, LAD myocardial blood flow, and regional myocardial wall thickening were measured. Fifteen minutes after the injection of bupivacaine, systolic and diastolic blood pressure decreased 24.1% and 26%, respectively, cardiac output decreased 25.6%, and mean coronary blood flow decreased 42%, compared to the saline control. Myocardial wall thickening in the LAD bed decreased 31%, although it remained unchanged in the normal myocardium. Epidural bupivacaine added to general anesthesia resulted in moderate hypotension. Distal to the coronary stenosis was a moderate decrease in regional myocardial function and a severe reduction in blood flow.
Anesthesia, Epidural↗
A case of juvenile form Pompe's disease manifested as chronic alveolar hypoventilation.
We describe a case of the juvenile form of Pompe's disease that presented as primary alveolar hypoventilation due to respiratory muscle involvement. This 17-year-old girl had been asymptomatic until this admission, although she had a delayed puberty. Arterial blood gas analysis, pulmonary function test as well as physical findings were compatible with chronic alveolar hypoventilation syndrome. Since she had lower extremity muscle weakness and pseudomyotonic discharge on electromyography a muscle biopsy was done, which revealed glycogen storage disease. The patient was managed successfully with nasal intermittent positive pressure ventilation.
Adolescent↗
[The pros and cons of soft contact lenses].
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Aphakia, Postcataract↗
Cardiac arrest due to a vagal reflex potentiated by thoracic epidural analgesia.
Reflex bradycardia and cardiac arrest may be the result of a vagal reflex, which can occur during a variety of surgical procedures. We report a patient who developed cardiac arrest as a result of a vagal reflex that was potentiated by thoracic epidural analgesia during general anaesthesia. A 53-year-old man was scheduled for subtotal gastrectomy because of an early gastric adenocarcinoma. After an epidural catheter had been inserted, general anaesthesia was induced. During surgery, an abdominal self-retaining retractor was set up but bradycardia and cardiac arrest developed. The patient returned to a normal sinus rhythm after successful resuscitation. We conclude that bradycardia as a result of a vagal reflex is mediated by potent abdominal wall traction and is potentiated by epidural analgesia. Early diagnosis and proper treatment can allow a full recovery, even in high-risk patients.
Abdomen↗
High glucose solution and spent dialysate stimulate the synthesis of transforming growth factor-beta1 of human peritoneal mesothelial cells: effect of cytokine costimulation.
OBJECTIVE: To investigate the effect of high glucose and spent peritoneal dialysate on the transforming growth factor-beta1 (TGFbeta1) synthesis of cultured human peritoneal mesothelial cells (HPMCs) and to examine the effect of costimulation with high glucose or spent dialysate, and cytokines, interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNFalpha) on TGFbeta1 synthesis of HPMCs. DESIGN: HPMCs were exposed to different concentrations of glucose (30, 60, and 90 mmol/L) or spent peritoneal dialysate for 48 hours in the absence or presence of IL-1beta (1 ng/mL) and TNFalpha(1 ng/mL).TGFbeta1 mRNA expression was assessed by Northern blot analysis and TGFbeta1 protein release by Western blot analysis and enzyme-linked immunosorbent assay (ELISA). RESULTS: Exposure of HPMCs to high glucose conditions (30, 60, and 90 mmol/L of D-glucose) induced 2.3-, 3.6-, and 4.0-fold increases inTGFbeta1 mRNA expression of HPMC with enhancedTGFbeta1 protein synthesis and secretion into the media, whereas there were no significant changes in TGFbeta1 synthesis with equimolar concentrations of D-mannitol. Incubation with spent dialysate also significantly increased TGFbeta1 mRNA expression and protein secretion compared to control media (p < 0.05). Stimulation with IL-1beta (1 ng/mL) or TNFalpha (1 ng/mL) resulted in a significant increase in TGFbeta1 mRNA expression after 48 hours: 2.7 and 2.1 times the control level, respectively. However,TNFalpha-induced increase in TGFbeta1 mRNA expression was not translated intoTGFbeta1 protein secretion, while IL-1beta stimulation induced a significant increase in TGFbeta1 protein secretion as well as TGFbeta1 mRNA expression. Combined stimulation by high glucose or spent dialysate, together with IL-1beta or TNFalpha, showed a greater increase in TGFbeta1 mRNA expression and protein secretion compared to stimulation by high glucose or spent dialysate alone. CONCLUSION: Our results clearly show that high glucose solution and spent dialysate themselves might be sufficient to stimulate the production of TGFbeta1 by peritoneal mesothelial cells. In peritoneal dialysis patients, this state of chronic induction of TGFbeta1 is further exacerbated in the presence of peritonitis because of the stimulatory effect of proinflammatory cytokines, resulting in augmented TGFbeta1 synthesis, thus promoting peritoneal fibrosis.
Blotting, Northern↗