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D A Armstrong

Publications and source records attributed to D A Armstrong.

At least 19 recordsLinked to original sources

MCP-1 is highly expressed in peritoneum following midline laparotomy with peritoneal abrasion in a murine model.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, is a potent attractant of monocytes both in vitro and in vivo. However, its role in the repair of peritoneal injury is not well established. This study characterizes MCP-1 expression in surgical wounds following peritoneal abrasion in a murine model. METHODS: Twenty-five C57 BL6 female mice underwent a 2-cm midline laparotomy with mechanical abrasion of the right peritoneal wall. The mice were sacrificed at various times ranging from 0 to 7 days. Hemotoxylin and eosin stained sections and tissue extracts were made using peritoneal samples from abraded and unabraded areas in each mouse. An enzyme-linked immunosorbent assay was performed on the specimens to quantitate MCP-1 expression. Values were compared using a t-test. RESULTS: At baseline, there was minimal expression of MCP-1 (<5 pg/mg protein). Following surgery, MCP-1 levels at abraded sites were significantly higher than those at both baseline and unabraded sites at all times up to a week following surgery. Histologic evaluation revealed peritoneal thickening and leukocytic infiltration of only abraded surfaces. CONCLUSION: MCP-1 is highly expressed in peritoneum following laparotomy with peritoneal abrasion. Elevations in MCP-1 levels are identified within 6 h of surgery and persist for up to 1 week. The histologic differences between abraded and unabraded areas may be attributable to differences in MCP-1 expression. Further studies using recombinant MCP-1 and anti-MCP-1 antibody may elucidate this relationship.

Animals↗

Pharmacodynamic and pharmacokinetic properties of a premixed 85/15 human insulin preparation.

BACKGROUND: Many patients with diabetes use mixtures of fast-acting (regular human) insulin and intermediate-acting (neutral protamine Hagedorn [NPH]) insulin to control their blood glucose levels. Premixed insulin is available in a 70%/30% mixture and a 50%/50% mixture of NPH/regular human insulin. For some patients, however, a premixed formulation containing > or =30% regular human insulin can provide too much fast-acting insulin, potentially causing an increased risk for hypoglycemia in the early hours after injection. OBJECTIVE: The pharmacokinetic and pharmacodynamic properties of a premixed formulation of 85% NPH insulin and 15% regular human insulin (85/15) were compared with those of a premixed 70%/30% NPH/regular human insulin preparation and 100% NPH insulin. METHODS: A 12-hour euglycemic clamp approach was used to assess glucose-lowering effects and serum insulin levels in 36 healthy male volunteers in a single-dose (0.5 U/kg), randomized, double-blind, 3-period, crossover study. RESULTS: From 0 to 8 hours after injection, the glucose-lowering effects and serum insulin levels for the 85/15 premixed insulin preparation were significantly greater than those for NPH insulin (P < or = 0.05) but significantly less than those for the 70/30 premixed insulin preparation. The mean (+/- SEM) maximum glucose infusion rate (GIRmax) was 8+/-0.6 mg/(min x kg) for the 85/15 preparation, 7+/-0.6 mg/(min x kg) for NPH, and 9+/-0.6 mg/(min x kg) for the 70/30 preparation, with time to peak GIR (tmax(GIR)) occurring at 313, 360, and 272 minutes, respectively. Time to peak insulin levels did not differ significantly for the 3 preparations, but maximum serum insulin concentration (Cmax(ins)) was significantly different between the groups (70/30 premix: 54+/-2.2 microU/mL; 85/15 premix: 44+/-2.4 microU/mL; NPH: 35+/-1.7 microU/mL). Glucodynamic effect and serum insulin levels did not differ significantly among preparations during the interval from 8 to 12 hours after injection. Mean serum C-peptide levels ranged from -0.6 to 1.0 ng/mL for each preparation during the 12-hour period after injection. CONCLUSIONS: The 85/15 premixed insulin preparation demonstrated clinical pharmacokinetic and pharmacodynamic properties that were intermediate between, and significantly different from, those of NPH insulin and the 70/30 premixed insulin preparation.

Adolescent↗

Effects of structure on alpha C-H bond enthalpies of amino acid residues: relevance to H transfers in enzyme mechanisms and in protein oxidation.

The bond dissociation enthalpies (BDE) of all of the amino acid residues, modeled by HC(O)NHCH(R)C(O)NH(2) (PH(res)), were determined at the B3LYP/6-31G//B3LYP/6-31G level, coupled with isodesmic reactions. The results for neutral side chains with phi, psi angles approximately 180 degrees, approximately 180 degrees in ascending order, to an expected accuracy of +/-10 kJ mol(-)(1), are Asn 326; cystine 330; Asp 332; Gln 334; Trp 337; Arg 340; Lys 340; Met 343; His 344; Phe 344; Tyr 344; Leu 344; Ala 345; Cys 346; Ser 349; Gly 350; Ile 351; Val 352; Glu 354; Thr 357; Pro-cis 358; Pro-trans 369. BDEs calculated at the ROMP2/6-31G//B3LYP/6-31G level exhibit the same trends but are approximately 7 kJ mol(-)(1) higher. All BDEs are smaller than those of typical secondary or tertiary C-H bonds due to the phenomenon of captodative stabilization. The stabilization is reduced by changes in the phi,psi angles. As a result the BDEs increase by about 10 kJ mol(-)(1) in beta-sheet and 40 kJ mol(-)(1) in alpha-helical environments, respectively. In effect the alpha C-H BDEs can be "tuned" from about 345 to 400 kJ mol(-)(1) by adjusting the local environment. Some very significant effects of this are seen in the current literature on H-transfer processes in enzyme mechanisms and in oxidative damage to proteins. These observations are discussed in terms of the findings of the present study.

Amino Acids↗

Interleukin-10 suppresses IP-10 gene transcription by inhibiting the production of class I interferon.

Interleukin-10 (IL-10) selectively inhibited lipopolysaccharide (LPS)-induced chemoattractant cytokine gene expression: levels of IP-10 mRNA were markedly suppressed in IL-10-treated mouse peritoneal macrophages, whereas the expression of the RANTES mRNA was only modestly reduced. IL-10 inhibited IP-10 mRNA accumulation by reducing IP-10 gene transcription as demonstrated by nuclear run-on analysis. Interestingly, the ability of IL-10 to inhibit expression of IP-10 was dependent on the inducing stimulus; IL-10 did not suppress interferon gamma (IFNgamma)- or IFNbeta-stimulated IP-10 transcription or mRNA accumulation. These results suggested that IL-10 might act indirectly to suppress IP-10 expression by inhibiting LPS-induced class I IFN production. This hypothesis was supported by the following observations. First, LPS-induced IP-10 mRNA expression was blocked in cells cotreated with cycloheximide. Second, IL-10 inhibited the production of IFN/beta-mediated antiviral activity. Finally, the IL-10-mediated suppression of LPS-stimulated IP-10 production could be rescued by cotreatment with IFNbeta.

Animals↗

Effects of nonesterified fatty acids on glucose metabolism after glucose ingestion.

Impaired suppression of plasma nonesterified fatty acids (NEFAs) after glucose ingestion may contribute to glucose intolerance, but the mechanisms are unclear. Evidence that insulin inhibits hepatic glucose output (HGO), in part by suppressing plasma NEFA levels, suggests that impaired suppression of plasma NEFA after glucose ingestion would impair HGO suppression and increase the systemic delivery of glucose. To test this hypothesis, we studied glucose kinetics (constant intravenous [3-3H]glucose [0.4 microCi/min], oral [1-14C]glucose [100 microCi]), whole-body substrate oxidation, and leg glucose uptake in eight normal subjects (age, 39 +/- 9 years [mean +/- SD]; BMI, 24 +/- 2 kg/m2) in response to 75 g oral glucose on two occasions. In one study, plasma NEFAs were prevented from falling by infusion of 20% Liposyn (45 ml/h) and heparin (750 U/h). Plasma glucose rose more rapidly during lipid infusion (P < 0.05), and mean levels tended to be higher after 120 min (6.45 +/- 0.41 vs. 5.81 +/- 0.25 SE, 0.1 < P < 0.05, NS); peak glucose levels were similar. Total glucose appearance (Ra) was higher during lipid infusion due to a higher HGO (28.4 +/- 1.0 vs. 21.2 +/- 1.5 g over 4 h, P < 0.005). Total glucose disposal (Rd) was also higher (88 +/- 2 vs. 81 +/- 3 g in 4 h, P < 0.05). Plasma insulin rose more rapidly after glucose ingestion with lipid infusion, and leg glucose uptake was 33% higher (P < 0.05) during the 1st hour. During lipid infusion, subjects oxidized less glucose (47 +/- 3 vs. 55 +/- 2 g, P < 0.05) and more fat (7.1 +/- 0.8 vs. 3.9 +/- 0.9 g, P < 0.02). In summary, 1) impaired suppression of NEFAs after oral glucose impairs insulin's ability to suppress HGO, and 2) in normal subjects the greater insulin response compensates for the increased systemic glucose delivery by increasing peripheral glucose Rd.

Adult↗

Clinical pathway management of total knee arthroplasty.

Using a retrospective cohort study design, the authors examined complications, readmissions, morbidity and mortality, and function scores in two groups of patients attended by the same surgeon for the year before and the year after the implementation of an outcomes management program with clinical pathways for patients undergoing total knee arthroplasty at an academic health center. The effectiveness of the pathway constantly was adjusted using variance analysis and continuous quality improvement techniques. This program reduced the length of stay by 57% from a premanagement value of 10.9 +/- 5.4 days in 1994 (Group 1) to 4.7 +/- 1.4 days in 1996 (Group 2). Hospital costs (based on an inflation adjusted cost to charge ratio) for all total knees were reduced 11% from $13,328 +/- $3905 in 1994 to $11,862 +/- $4763 in 1996. Preoperative and postoperative knee scores were 41.1 +/- 16.3 and 84.2 +/- 16.0 for Group 1 and 42.5 +/- 13.0 and 87.0 +/- 10.4 for Group 2, respectively. There was no statistically significant difference between the preoperative or the postoperative knee scores of Groups 1 and 2. The application of clinical pathways, variance analysis, and continuous quality improvement toward the treatment of patients who had total knee arthroplasty at an academic health center resulted in significant savings in length of stay without adversely affecting overall outcome.

Academic Medical Centers↗

Oxidized LDL ceroid, and prostaglandin metabolism in human atherosclerosis.

A noted histological feature of human atherosclerotic lesions upon dissection is the presence of a 'pigment' referred to as ceroid; however the significance of ceroid in human fatty streaks and atherosclerotic plaques is not certain. The research focus to this point has presumed that ceroid synthesis and intracellular accumulation is harmful and may have adverse effects on lesion progression or reversibility. Alternatively, ceroid production may be a defense mechanism employed by cells in the artery wall to prevent uncontrolled synthesis and release of prostaglandins (PGs) or prostaglandin-precursors locally. Export of PGs or PG precursors may promote blood platelet aggregation at the site of export. A feedback inhibition mechanism will arrest the cellular export of prostaglandins, thus ending a potentially disastrous premature clotting event.

Arteriosclerosis↗

AIDS-related vacuolar myelopathy is not associated with coinfection by human T-lymphotropic virus type I.

Assessment of antibodies against human T-lymphotropic virus type I (HTLV-I) by enzyme-linked immunoassay, immunofluorescence, and Western blot was undertaken in patients with pathologically or clinically diagnosed acquired immunodeficiency syndrome-related vacuolar myelopathy to determine whether this retrovirus could be etiologically implicated in this disorder. No serological evidence for HTLV-I was found in the patients with vacuolar myelopathy, though 1 patient with an atypical myelopathy did have antibodies against HTLV-I.

Acquired Immunodeficiency Syndrome↗

Antipyretics.

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Aminophenols↗

Effects of oxytocin on placental retention following dystocia.

A double blind randomised clinical trial was performed to assess the effects of oxytocin on the duration of placental retention following dystocia. If the placenta remained attached to the uterus immediately following assisted delivery of a calf, and was not expelled in the period taken to complete the protocol, an intramuscular injection of either 3 ml (60 USP units) of oxytocin or 3 ml of 0.9 per cent physiological saline was given to the cow. Each farmer was asked to observe the cow to determine the time of placental expulsion. In 55 cases available for analysis there was no significant difference between the treatment and control groups for percentage of placental retention at days 1, 2 or 3 post partum.

Animals↗

Reduction of lumichrome by the radical anions of CO2 and lipoamide.

The uptake of reducing equivalents of X CO-2 by lumichrome in spectrophotometric titrations has been re-examined in the light of a recently reported extinction coefficient of 10 500 M-1 cm-1 at pH 6, which is in agreement with 10 270 +/- 100 M-1 cm-1 determined here. The average uptake was 1.8 +/- 0.1, independent of pH in the range 6.3-9.0. The major product appears to be a dihydro-alloxazine, which can be reoxidized quantitatively to lumichrome by X Br-2 radicals or by O2. As in the case of dihydroflavins, oxidation by O2 is biphasic. As in the case of flavins, a two electron reduction of lumichrome was also observed with the disulphide monoanion of lipoamide (LS X 2-), but that reduction does not go to 100 per cent yield. Contrary to our earlier conclusions, which were based on an erroneous extinction coefficient, the combination of lumichrome radicals (2 X LcH----HLc--LcH) was of relatively little (less than or equal to 20 per cent) importance, and the behaviour of lumichrome on treatment with reducing species was rather similar to that of flavins.

Anions↗

Reactions of lumiflavin and lumiflavin radicals with .CO2- and alcohol radicals.

The kinetics of reaction of oxidized lumiflavin (F0) with the radicals .CO2(-), CH3CHOH, and (CH3)2COH have been investigated at pH 7 and 24 +/- 1 degree C by the pulse radiolysis technique. The radicals have been shown to react with lumiflavin with second-order rate constants of 36 +/- 4, 26 +/- 3, and 20 +/- 3 in units of 10(8) M-1 s-1, respectively. These rate constants are close to the diffusion limit. The main product in each case was the lumiflavin semiquinone radical FH.. By utilization of long pulses (approximately 100 mus), it was shown that the reaction FH. + .AH(alpha) leads to FH- + A(alpha) + H+ [.AH(alpha) = .CO2(-), CH3CHOH, or (CH3)2COH] proceeded for all three types of .AH(alpha) radical with second-order rate constants of 17 (+4,-3), 9 (+5,-3), and 9 (+4,-3), respectively, in the above units. The beta-carbon radical .CH2CH(OH)CH3 added to .FH, forming an alkylated flavin, while the .CH2CH2OH radical appeared to be capable of addition or hydrogen atom donation to .FH.

Alcohols↗

Reduction, oxidation, and addition reactions between free radicals and flavins.

Flavins and reduced flavins were reacted with a variety of free radicals produced in dilute aqueous solution at pH 7 +/- 0.1 by radiation chemical methods. The radical .CH2C(CH3)2OH and the aliphatic beta, gamma, and delta radicals of ethanol, 2-propanol, and 1-butanol added to the radical form of flavin adenine dinucleotide (FAD) (FH.) to yield products that could not be reoxidized to flavin by oxygen. The first radical also added to FAD but with a much lower efficiency. In contrast, the alpha-carbon radicals .CH(OH)CH2OH, CH3(-3) CHOH, and (CH3)2COH appeared to undergo two reactions: FH. + RR'COH leads to FH- + RR'C==O FH. + RR'COH leads to FH- + RR'C==O + H+ The formate radical anion .CO2(-) reacted similarly, producing stoichiometric two-electron reduction of riboflavin and lumiflavin as well as FAD. While eaq- also seemed capable of this, it was found to react irreversibly with FADH2, which makes it a poor reagent for producing the dihydroflavin. The dihydro form of FAD was reoxidized to FAD by the species RS. and .BR2(-). In contrast to FAD, the alloxazine lumichrome underwent only one-electron reduction and oxidation by .CO2(-) and .Br2(-), respectively.

Alcohols↗

Superinfection: another look.

Superinfection in the compromised host often poses a diagnostic and therapeutic dilemma for the physician who is concerned that a perplexing array of microorganisms might be involved. We believe that the differential diagnosis list can often be narrowed considerably by separating superinfection in the compromised host into five convenient categories: (1) infections due to the underlying disease itself; (2) infections due to the underlying disease plus therapy for that disease; (3) infections due solely to medicaments, operations, or procedures; (4) infections increased in severity but probably not in incidence; and (5) societally related infections. Use of this or a similar categorization should result in a more rational approach to differential diagnosis, should encourage a more focused diagnostic work-up, whould reduce the necessity for invasive procedures, should provide the microbiology laboratory information about specific organisms that should be sought sedulously, and should permit the selection of a more rational antimicrobial regimen prior to the availability of definitive microbiologic information.

Adult↗

Anthelmintic efficacy of albendazole in calves with naturally acquired Fasciola hepatica infections.

The anthelmintic efficacy of albendazole was evaluated as an oral drench at dosages of 15.0, 10.0, and 7.5 mg/kg of body weight in 3 groups crossbred Brahman calves (n = 12 group) infected with Fasciola hepatica. Although posttreatment fluke ova counts for the 3 albendazole treatment groups were significantly (P less than 0.01) lower (av 82%) than were counts in nontreated calves, there were no significant differences in the responses to the different albendazole treatments. At necropsy, adult fluke counts in treated calves were lower (P less than 0.05) than were counts in nontreated calves, but as with ova counts, a dose-related trend was not noticed. Efficacy against adult flukes was 63.4%, 50.0%, and 56.6% for 15.0, 10.0, and 7.5 mg/kg, respectively. Activity against immature flukes was not observed in calves given the 10.0 and 7.5 mg/kg, but there was a 36% decrease of flukes in those calves given 15.0 mg/kg. Significant decreases (P less than 0.05) in fluke ova viability were observed for the 3 treatment groups in which 12.9% of ova collected at necropsy failed to embryonate (control group av 6.7%). Posttreatment weight changes were not significantly different, although gains were greater within albendazole treatment groups. Decreases in gastrointestinal parasite ova counts after treatment were 98%, 93%, and 93% for groups given 15.0, 10.0, and 7.5 mg/kg, respectively. Ova counts in nontreated calves increased 26.2% during the same period.

Albendazole↗