Lactate measurement: plasma or blood?
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Biomedical subjects
Publications and source records attributed to R W Carlson.
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In order to elucidate the role of arachidonic acid in the pathogenesis of ozone-induced pulmonary edema, isolated rat lungs were exposed to 14C-arachidonic acid in the presence or absence of ozone and the incorporation of radiolabelled arachidonate into pulmonary cell lipids was studied. The perfusates from these studies were also subjected to differential extraction and thin layer chromatography (t.l.c.) to determine synthesis of both cyclo-oxygenase and lipoxygenase products. In the presence of an edemagenic concentration of ozone, isolated lungs incorporated significantly less exogenous arachidonic acid into phosphatidyl choline and phosphatidyl ethanolamine, whereas incorporation into phosphatidyl inositol or serine was not affected. The edemagenic concentration of ozone also increased production of a variety of arachidonic acid metabolites via cyclo-oxygenase and lipoxygenase pathways. In separate studies, a similar ozone exposure did not affect 14CO2 production, resulting from the metabolism of 14C-antipyrine by mixed function oxidases (MFO). Similarly, an edemagenic concentration of ozone did not affect pulmonary angiotensin converting enzyme activity (ACE) as determined by the rate of formation of 14C-hippuric acid from 14C-hippuryl-histidyl-leucine (14C-HHL). Thus, acute ozone exposure is specifically associated with a reduced incorporation of arachidonate into phospholipids and with an increased conversion of arachidonate into bio-active metabolites.
Carbetimer (carboxyimamidate) was administered at a dose of 6,500 mg/m2/day intravenously for 5 consecutive days to 14 patients with measurable metastatic or recurrent colorectal cancer in a single institution phase II study of the Northern California Oncology Group. A total of 38 cycles of therapy were administered; nine patients completed at least three cycles of treatment. No partial or complete responses were observed. One patient did have a greater than 50% response in the liver while developing new retroperitoneal lymphadenopathy and is considered a nonresponder. Carbetimer was well tolerated with elevations of calcium from 10.2 to 12.5 mg/dl in nine patients, prolongation of prothrombin time and partial thromboplastin time in 14 patients, proteinuria in 10 patients, dizziness in six patients, nausea in two patients, and venous pain during infusion in three patients. Myelosuppression was not observed. Carbetimer at this dose and schedule is inactive in the treatment of colorectal cancer.
Although systolic dysfunction of the left ventricle has been characterized in septic shock (SS) and sepsis without shock (SWS), diastolic abnormalities are less well characterized. Diastolic filling was determined using pulsed Doppler transmitral spectral tracings in 13 patients with SS, ten patients with SWS, and 33 normal controls. Diastolic filling variables and heart rate were similar in patients with SS and SWS. The SS and SWS patients had an abnormal pattern of diastolic filling compared with controls and were characterized by an increase in peak atrial velocity (70 +/- 20 cm/sec SS, 84 +/- 18 cm/sec SWS vs. 56 +/- 11 cm/sec controls, p less than .05), decreased peak rapid filling velocity/peak atrial filling velocity (1.1 +/- 0.3, SS, 1.1 +/- 0.2 SWS vs. 1.5 +/- 0.4 controls, p less than .05), increased atrial filling fraction (39 +/- 11 SS, 42 +/- 6 SWS vs. 30 +/- 10 controls, p less than .05) and prolongation of atrial filling period as a function of the diastolic filling period (0.48 +/- 0.10 SS, 0.43 +/- 0.10 SWS vs. 0.30 +/- 0.07 controls, p less than .05). Heart rate was higher in SS and SWS compared with controls (116 +/- 15 beat/min SS, 110 +/- 26 beat/min SWS vs. 73 +/- 12 beat/min controls, p less than .05). In patients with SS and SWS, there is increased reliance on atrial systolic contribution to diastolic filling. We conclude that diastolic dysfunction occurs with systemic infections.
Two mutant derivatives of Rhizobium leguminosarum ANU843 defective in lipopolysaccharide (LPS) were isolated. The LPS of both mutants lacked O antigen and some sugar residues of the LPS core oligosaccharides. Genetic regions previously cloned from another Rhizobium leguminosarum wild-type isolate, strain CFN42, were used to complement these mutants. One mutant was complemented to give LPS that was apparently identical to the LPS of strain ANU843 in antigenicity, electrophoretic mobility, and sugar composition. The other mutant was complemented by a second CFN42 lps genetic region. In this case the resulting LPS contained O-antigen sugars characteristic of donor strain CFN42 and reacted weakly with antiserum against CFN42 cells, but did not react detectably with antiserum against ANU843 cells. Therefore, one of the CFN42 lps genetic regions specifies a function that is conserved between the two R. leguminosarum wild-type isolates, whereas the other region, at least in part, specifies a strain-specific LPS structure. Transfer of these two genetic regions into wild-type strains derived from R. leguminosarum ANU843 and 128C53 gave results consistent with this conclusion. The mutants derived from strain ANU843 elicited incompletely developed clover nodules that exhibited low bacterial populations and very low nitrogenase activity. Both mutants elicited normally developed, nitrogen-fixing clover nodules when they carried CFN42 lps DNA that permitted synthesis of O-antigen-containing LPS, regardless of whether the O antigen was the one originally made by strain ANU843.
The lipopolysaccharide (LPS) of Bradyrhizobium japonicum 61A123 was isolated and partially characterized. Phenol-water extraction of strain 61A123 yielded LPS exclusively in the phenol phase. The water phase contained low-molecular-weight glucans and extracellular or capsular polysaccharides. The LPSs from B. japonicum 61A76, 61A135, and 61A101C were also extracted exclusively into the phenol phase. The LPSs from strain USDA 110 and its Nod- mutant HS123 were found in both the phenol and water phases. The LPS from strain 61A123 was further characterized by polyacrylamide gel electrophoresis, composition analysis, and 1H and 13C nuclear magnetic resonance spectroscopy. Analysis of the LPS by polyacrylamide gel electrophoresis showed that it was present in both high- and low-molecular-weight forms (LPS I and LPS II, respectively). Composition analysis was also performed on the isolated lipid A and polysaccharide portions of the LPS, which were purified by mild acid hydrolysis and gel filtration chromatography. The major components of the polysaccharide portion were fucose, fucosamine, glucose, and mannose. The intact LPS had small amounts of 2-keto-3-deoxyoctulosonic acid. Other minor components were quinovosamine, glucosamine, 4-O-methylmannose, heptose, and 2,3-diamino-2,3-dideoxyhexose. The lipid A portion of the LPS contained 2,3-diamino-2,3-dideoxyhexose as the only sugar component. The major fatty acids were beta-hydroxymyristic, lauric, and oleic acids. A long-chain fatty acid, 27-hydroxyoctacosanoic acid, was also present in this lipid A. Separation and analysis of LPS I and LPS II indicated that glucose, mannose, 4-O-methylmannose, and small amounts of 2,2-diamino-2,3-dideozyhexose and heptose were components of the core region of the LPS, whereas fucose, fucosmine, mannose, and small amounts of quinovosamine and glucosamine were components of the LPS O-chain region.
We reviewed the changes in Do2 and Vo2 in 58 patients with ARDS after interventions which included fluid loading, blood transfusion, and PEEP. After a significant change in Do2, patients with lactic acidosis (lactate level greater than 2.4 mmol/L) exhibited significant corresponding changes in Vo2 (p less than 0.001); however, no change in Vo2 was observed in patients without lactic acidosis (1-beta greater than 0.8). We conclude that a biphasic pattern of oxygen utilization in patients with ARDS emerges when subsets of patients with and without lactic acidosis are compared. Lactic acidosis, a marker of anaerobic metabolism, may be a characteristic of patients with ARDS who exhibit changes in Vo2 that are dependent on changes in Do2.
This study determined whether a sepsis-associated increase in cyclooxygenase products altered the pulmonary vascular response to the thromboxane A2 mimic, 9,11-dideoxy-11a,9a-epoxymethano-prostaglandin F2 alpha (U46619). Rats were anesthetized (50 mg/kg of sodium pentobarbital i.p.), and sepsis was induced by cecal ligation and puncture. Four hours later, pulmonary effluent immunoreactive thromboxane (iTXB2) levels were significantly increased (156.8%) and pulmonary vascular reactivity to U46619 (50-200 ng) was significantly (P less than .05) decreased compared to lungs from nonseptic controls. This decreased vascular reactivity was not seen in lungs from cecally ligated rats challenged with angiotensin II (5-200 ng). Sham surgery did not alter pulmonary iTXB2 synthesis nor did it result in a depressed vascular response to U46619. Rats pretreated with ibuprofen (15 mg/kg i.v.) did not show the sepsis-associated increase in iTXB2 levels nor was a decrease in pulmonary vascular reactivity to U46619 observed. These data indicate that a sepsis-associated increase in TXA2 and/or other cyclooxygenase products can alter the pulmonary vascular response to the TXA2 mimic, U46619.
Seventy-five patients with moderate to severe cancer pain were randomly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally, acetaminophen 600 mg plus codeine 60 mg orally, or placebo, followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days. Patient characteristics were similar among the treatment groups. The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief. Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine, although there were no differences in mean daily ratings of overall effects for either study medication. Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine. We conclude that ketorolac has significant analgesic activity in patients with cancer pain, although its precise role in the treatment regimen of these patients remains undefined.
There are conflicting recommendations regarding the use of intravenous potassium chloride infusions for acute correction of hypokalemia. We examined the effects of 495 sets of potassium chloride infusions administered to a medical intensive care unit population. The infusion sets consisted of one to eight consecutive individual infusions, each containing 20 mEq of potassium chloride in 100 mL of saline administered. The mean preinfusion potassium level was 3.2 mmol/L, and the mean postinfusion potassium level was 3.9 mmol/L. The mean increment in serum potassium level per 20-mEq infusion was 0.25 mmol/L. No temporally related life-threatening arrhythmias were noted; however, there were 10 instances of mild hyperkalemia. Our data endorse the relative safety of using concentrated (200-mEq/L) potassium chloride infusions at a rate of 20 mEq/h via central or peripheral vein to correct hypokalemia in patients in the intensive care unit.
The structures for the core regions of the lipopolysaccharides (LPSs) from R. leguminosarum bv. phaseoli CE3 and two symbiotic mutants were determined by g.l.c.-m.s., proton nuclear magnetic resonance spectroscopy (n.m.r.), fast-atom-bombardment mass spectrometry (f.a.b.-m.s.), and by comparison with known structures from the LPS of R. leguminosarum bv. trifolii ANU843. The core oligosaccharides were separated into two components, P2-2 and P2-3, by gel-filtration chromatography using Bio-Gel P2. The P2-2 oligosaccharide from CE3 is a tetrasaccharide consisting of 3-deoxy-D-manno-2-octulosonic acid (Kdo), mannose, galactose and galacturonic acid. The mannosyl residue is alpha-linked to O-4 of Kdo, and the galactosyl and galactosyluronic residues are alpha-linked to O-4 and O-6, respectively, of the mannosyl residue. The P2-2 oligosaccharide from mutant CE109 is missing the galactosyluronic residue, while that from mutant CE309 is missing both the galactosyl and galactosyluronic residues. The P2-3 oligosaccharide from CE3 LPS is a trisaccharide consisting of two galactosyluronic residues alpha-linked to the O-4 and O-7 of Kdo. Fraction P2-3 from mutant CE309 has the same structure as CE3 P2-3. Fraction P2-3 from mutant CE109 contains galacturonic acid and Kdo, but its structure differs from that of CE3 P2-3.
A second core oligosaccharide fragment has been isolated and characterized from the lipopolysaccharide (LPS) of Rhizobium trifolii ANU 843. The oligosaccharide is a tetrasaccharide composed of galactose, galacturonic acid, mannose, and 3-deoxy-D-manno-2-octulosonic acid. The mannose residue is alpha-linked to the 4-position of 3-deoxy-D-manno-2-octulosonic acid and the galacturonic acid residue is alpha-linked to the 6-position of mannose. The galactose residue, which is acetylated at the 4-position, is attached to the 4-position of mannose by an alpha-linkage. All of the aldoses are in the pyranose form. The composition of the tetrasaccharide was determined by gas-liquid chromatography of the alditol acetate derivatives of the component monosaccharides. The configuration of anomeric linkages was determined by 1H NMR spectroscopy. Fast atom bombardment-mass spectrometry (FAB-MS) was performed on acetylated, per(trideutero)acetylated and underivatized tetrasaccharide giving sequence information in addition to information on the residue which was acetylated. Similar studies were performed on the oligosaccharide after reduction with sodium cyanoborohydride and peracetylation with labeled and unlabeled acetic anhydride as before. Further linkage and sequence analysis was obtained from methylation analysis, and from electron impact mass spectrometry of the per(trideutero)acetylated oligosaccharide and from collision-induced dissociation fast atom bombardment tandem mass spectrometry using linked scans at constant B/E on the cyanoborohydride-reduced, per (trideutero)acetylated oligosaccharide. The exact location of the acetyl group was deduced from 1H NMR double resonance experiments in conjunction with mass spectrometric data.
A new hydroxylated, very long-chain fatty acid has been isolated and characterized from the lipopolysaccharide (LPS) of Rhizobium trifolii ANU 843. The lipid A of the organism was degraded by mild alkali and borohydride and the products methylated, peracetylated, and fractionated on a C18 reverse-phase column. The major lipid fraction was reduced with lithium triethylborohydride, methylated, peracetylated, and subjected to thin layer chromatography. The methylated peracetylated acid and the reduced diacetylated diol (1,27-dihydroxyoctacosane diacetate) were isolated and characterized by mass spectrometry and 1H NMR spectroscopy using homonuclear decoupling. The identity and linkage of the new fatty acid in the lipopolysaccharide was confirmed by 1H NMR spectroscopy of purified lipid A fractions and similar NMR studies of lipid A after acylation by phenylisocyanate. In the native LPS, the 27-hydroxy C-28 fatty acid is acylated at the 27-hydroxy position by other 3-hydroxy fatty acids. About 50% of the total fatty acid content of the LPS of R. trifolii ANU 843 is 27-hydroxyoctacosanoic acid. This oxyacyloxy structure involving 27-hydroxyoctacosanoic appears to be the major structural feature of the lipid A of this organism.
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We developed a supportive care team for hopelessly ill patients in an urban emergency/trauma hospital. The team includes a clinical nurse specialist and a faculty physician as well as a chaplain and social worker. The supportive care team provides an alternative to intensive care or conventional ward management of hopelessly ill patients and concentrates on the physical and psychosocial comfort needs of patients and their families. We describe our experience with 20 hopelessly ill patients with multiple organ failure vs a similar group treated before the development of the supportive care team. Although there was no difference in mortality (100 percent), the length of stay in the medical ICU for patients with multiple organ failure decreased by 12 days to 6 days. Additionally, there were 50 percent fewer therapeutic interventions provided by the supportive care team vs intensive care or conventional ward treatment of multiple organ failure patients. We describe the methods that the supportive care team uses in an attempt to meet the physical and psychosocial comfort needs of hopelessly ill multiple organ failure patients and their families. This multidisciplinary approach to the care of the hopelessly ill may have applications in other institutions facing the ethical, medical, and administrative challenges raised by these patients.
Comparative studies were undertaken on the effects of ozone and t-butyl hydroperoxide (t-BuOOH) on alkane production, glutathione and lactate dehydrogenase (LDH) release from isolated rat lungs. Specifically, ethane and pentane production, as well as glutathione and LDH release were simultaneously determined at different time intervals from the isolated lung preparation in the absence and presence of toxic concentrations of ozone or t-BuOOH. When compared to control conditions, both toxic agents produced a marked decrease in the dry weight to wet weight ratios, reflecting the development of acute pulmonary edema. These toxic agents also caused a marked increase in the efflux of glutathione into the effluent. A much higher glutathione efflux into the effluent was observed during t-BuOOH perfusion in comparison to ozone exposure. In parallel with the enhancement of glutathione release a significant increase in ethane production was also observed during t-BuOOH perfusion. However, the production of either alkane by ozone inhalation was not significantly different from that in the control conditions. Unlike glutathione release, there was no marked increase of LDH release into the effluent following exposure to t-BuOOH or ozone. This suggests that the observed increase in glutathione release caused by t-BuOOH or ozone treatment was not associated with non-specific destruction of cell membrane integrity.
To evaluate a new multilumen central venous catheter we prospectively compared the infection rates of 63 single-lumen and 157 triple-lumen catheters in 145 critically ill patients. Using acute physiology scores, severity of illness was shown to be similar in the two patient groups. There were no significant differences in the rate of catheter colonization or catheter-related sepsis comparing single-lumen with triple-lumen catheters. However, the use of total parenteral nutrition or insertion at the femoral vein site significantly increased the rate of colonization. The only factor that was clearly associated with catheter sepsis was the duration of catheterization. Catheter sepsis increased from 1.5% to 10% when the period of catheterization exceeded 6 days. We conclude that the use of triple- and single-lumen central venous catheters in critically ill patients entails similar risks of infection.