Search PubMed⌕ Search

Biomedical subjects

K Duke

Publications and source records attributed to K Duke.

At least 19 recordsLinked to original sources
PubMed2004

Constant infusion of epinephrine, but not bolus treatment, improves haemodynamic recovery in anaphylactic shock in dogs.

OBJECTIVE: Epinephrine (Epi) is the treatment of choice for reversing cardiovascular collapse in anaphylactic shock (AS). In this condition, most treatment guidelines have been anecdotally derived and no randomized clinical trials have been conducted. In the present study, we examined the time course of haemodynamic recovery in a canine model of AS when Epi was administered at the initiation of allergen challenge before fully developed shock had occurred. METHODS: Randomized, controlled, crossover studies were performed approximately 3-5 weeks apart in ragweed-sensitized dogs while the animals were ventilated and anaesthetized. Epi was administered by bolus intravenous (i.v.), subcutaneous (s.c.), intramuscular (i.m.) routes and by continuous i.v. infusion (CI). The findings obtained in the Epi treatment (T) studies were compared with those found in a no treatment (NT) study. In the bolus studies, Epi was administered at 0.01 mg/kg, while in the CI study, the dose of Epi was titrated to maintain mean arterial pressure (MAP) at 70% of preshock levels. MAP, cardiac output (CO), stroke volume (SV), and pulmonary wedge pressure (Pwp) were determined over a 3 h period. RESULTS: In the CI study, haemodynamics (CO, MAP, and SV) were significantly higher than those measured in the NT study and the bolus studies over approximately the first hour of the study. In the CI study, the amount of Epi infused was significantly less than in the bolus studies. CONCLUSION: When administered at the initiation of allergen challenge, bolus treatment of Epi by i.m., i.v., or s.c. routes caused limited haemodynamic improvement in AS. In contrast, constant infusion of Epi at a lower total dose produced significant haemodynamic improvement. Within the limits of this anaesthetized canine model, the results suggest that CI should be the preferred route in the treatment of AS when this treatment option is available.

Allergens↗
PubMed2003

Identification and characterization of peptide probes directed against PKCalpha conformations.

Phage display is a powerful technology that allows identification of high affinity peptides that bind specifically to a given molecular target. Using a highly complex peptide display library, we have identified separate classes of peptides that bind to protein kinase C alpha (PKCalpha) only under activation conditions. Furthermore, peptide binding was specific to PKCalpha and not to any of the other closely related PKC isoforms. The conformational and isoform specificity of the peptide binding was demonstrated using surface plasmon resonance as well as time-resolved fluorescence assays. Kinase assays showed that these peptides were not direct substrates for PKC nor did they inhibit phosphorylation of PKC substrates. These peptides are most likely directed against protein-protein interaction sites on PKC. The data presented here offers another example of application of phage display technology to identify conformation-dependent peptide probes against therapeutically important drug targets. These peptides are ideally suited to be used as surrogate ligands to identify compounds that bind specifically to PKCalpha, as well as conformational probes to detect activated forms of PKCalpha.

Amino Acid Sequence↗
PubMed2002

Study of patient positioning on a dynamic frame for scoliosis surgery.

The goal of this clinical trial was to measure patient geometry on a dynamic positioning frame in various prone positions. Fourteen subjects (2 males and 12 females) were recruited from the scoliosis clinic at Ste-Justine Hospital on a volunteer basis. The subjects were AIS patients who were potential candidates for surgery. The Cobb angle, averaged 50 degrees (32 degrees-64 degrees). The mean age was 14.1 years (11-17). A Polaris system (Northern Digital inc, Canada) with 10 passive reflective markers was used to measure various indices of the patient's trunk geometry. Acquisitions were made while the unanaesthetized patient was in five different prone positions: I similar to the standard positioning on a Relton-Hall frame; II addition of a force applied to the ribcage at the apex of the curve; III application of a force at the apex of the curve in the lumbar region; IV, the shoulder pads were elevated to increase the patient's kyphosis; V adjustment of each pad and the application of thoracic and lumbar forces to obtain an optimal correction. The measurements of trunk geometry at each position were compared using position I as a base. A paired student t-test determined a significant difference between positions. When comparing position I to position II there was a significant difference and correction of the rib hump. There was also a significant change in shoulder angle that resulted in over correction. Position III had a significantly negative change in the rib hump. During position IV, there was a measurable increase in kyphosis. During the optimal correction, position V, a significant increase in spine length was observed as well as a significant correction in rib hump and shoulder angle. Patient trunk geometry can be improved by the application of different forces on a dynamic positioning frame. Caution is necessary as over correction and unintended negative effects were observed. The optimal patient position has not yet been found and future studies are directed at determining this.

Adolescent↗
PubMed2001

A gene expression map for Caenorhabditis elegans.

We have assembled data from Caenorhabditis elegans DNA microarray experiments involving many growth conditions, developmental stages, and varieties of mutants. Co-regulated genes were grouped together and visualized in a three-dimensional expression map that displays correlations of gene expression profiles as distances in two dimensions and gene density in the third dimension. The gene expression map can be used as a gene discovery tool to identify genes that are co-regulated with known sets of genes (such as heat shock, growth control genes, germ line genes, and so forth) or to uncover previously unknown genetic functions (such as genomic instability in males and sperm caused by specific transposons).

Algorithms↗
PubMed2001

Genome-wide analysis of developmental and sex-regulated gene expression profiles in Caenorhabditis elegans.

We have constructed DNA microarrays containing 17,871 genes, representing about 94% of the 18,967 genes currently annotated in the Caenorhabditis elegans genome. These DNA microarrays can be used as a tool to define a nearly complete molecular profile of gene expression levels associated with different developmental stages, growth conditions, or worm strains. Here, we used these full-genome DNA microarrays to show the relative levels of gene expression for nearly every gene during development, from eggs through adulthood. These expression data can help reveal when a gene may act during development. We also compared gene expression in males to that of hermaphrodites and found a total of 2,171 sex-regulated genes (P < 0.05). The sex-regulated genes provide a global view of the differences between the sexes at a molecular level and identify many genes likely to be involved in sex-specific differentiation and behavior.

Aging↗
PubMed2000

Impaired sarcoplasmic calcium release inhibits myocardial contraction in experimental sepsis.

PURPOSE: In septic shock, myocardial dysfunction develops over the course of illness, but the mechanism of this depression is not clear. In this study, mechanisms of myocardial dysfunction were examined in a porcine model of Escherichia coli sepsis. MATERIALS AND METHODS: Animals were subjected to 4 hours of bacteria infusion (n = 5) (septic group) or saline infusion (n = 5) (nonseptic group), after which trabeculae were removed from the right ventricle and placed into a recirculating water bath. Measurements of steady-state contraction (SSC) were obtained at 0.5, 1, and 2 Hz. Indirect indices were used to assess abnormalities in myocardial calcium metabolism in sepsis. Extrasystoles (ES) were used to assess transsarcolemmal (TSL) calcium flux and were measured at 300 milliseconds, 400 milliseconds, and 500 milliseconds after the preceding stimulus. Postrest contraction (PRC) is an indicator of SR recirculation from the uptake to the release site and was obtained after interposing intervals of rest between steady-state beats at 0.5 Hz. Rapid-cooling contracture (RCC) is an indicator of sarcoplasmic reticulum (SR) content and was obtained at 0.5, 1, and 2 Hz and after interposing intervals of rest at 0.5 Hz. RESULTS: SSC was not different between groups at 0.5 Hz, but compared with the nonseptic group, SSC decreased at 1 and 2 Hz in the septic group (P < .05). PRC and TSL were not different between groups. During rest intervals, calcium leaks out of SR through the ryanodine channel (ie, SR calcium release channel). In the septic group, as assessed by RCC, SR calcium leak was less than that found in the nonseptic group. CONCLUSION: These results indicate that myocardial dysfunction in sepsis is frequency dependent, and that the mechanism is most likely caused by inhibition of SR calcium release owing to blockade of the ryanodine channel.

Analysis of Variance↗
PubMed2000

Redox chemistry in laccase-catalyzed oxidation of N-hydroxy compounds.

1-Hydroxybenzotriazole, violuric acid, and N-hydroxyacetanilide are three N-OH compounds capable of mediating a range of laccase-catalyzed biotransformations, such as paper pulp delignification and degradation of polycyclic hydrocarbons. The mechanism of their enzymatic oxidation was studied with seven fungal laccases. The oxidation had a bell-shaped pH-activity profile with an optimal pH ranging from 4 to 7. The oxidation rate was found to be dependent on the redox potential difference between the N-OH substrate and laccase. A laccase with a higher redox potential or an N-OH compound with a lower redox potential tended to have a higher oxidation rate. Similar to the enzymatic oxidation of phenols, phenoxazines, phenothiazines, and other redox-active compounds, an "outer-sphere" type of single-electron transfer from the substrate to laccase and proton release are speculated to be involved in the rate-limiting step for N-OH oxidation.

Acetaminophen↗
PubMed2000

Impaired hepatic extraction and increased splanchnic production contribute to lactic acidosis in canine sepsis.

In septic shock, the extent to which lactic acidosis (LA) is a consequence of splanchnic lactate overproduction (SLP) or impaired hepatic lactate extraction (HLE) is not clear. We examined SLP and HLE in E. coli sepsis in dogs. We further determined the effects of vasopressor treatments, which included phenylephrine, dopamine, norepinephrine, and a combination of dobutamine and norepinephrine treatment, on SLP and HLE in respective groups. The animals were studied while anesthetized and ventilated. During sepsis, SLP increased as compared with presepsis (-0.017 versus 0.07 mmol/min, p < 0.05), but this increase could not be explained by reduced splanchnic oxygen delivery (SOD). During sepsis, HLE increased as compared with baseline (0.8 versus 8%, p < 0.05), but was significantly lower than that found during lactic acid loading in nonseptic dogs. None of the vasopressor treatments had a detrimental effect on SLP. These results indicate that LA in sepsis occurs secondary to an increase in splanchnic lactate production that is not related to reduced splanchnic oxygen delivery, as well as to a decrease in hepatic lactate extraction. Effects of different vasoactive agents did not alter either splanchnic lactate production or hepatic lactate extraction in this sepsis model.

Acidosis, Lactic↗
PubMed1999

Role of autacoids in cardiovascular colapse in anaphylactic shock in anaesthetized dogs.

OBJECTIVE: In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins (prost), and leukotrienes (leuk) on causing cardiovascular collapse and the extent to which receptor blocking agents and pathway inhibitors may prevent this collapse are not clear. METHODS: In randomized design, we investigated whether blockade of histamine H1, H2, and H3 receptors or inhibition of the cyclooxygenase (cyclo) and lipoxygenase pathways (lipox) prevented AS in ragweed sensitized dogs. Seven dogs were studied under pentobarbital anesthesia in which the treatment studies were approximately 2 weeks apart. RESULTS: During H1 receptor blockade, the decreases in blood pressure and cardiac output otherwise observed in AS were attenuated (P < 0.05) and the release of prost, thromboxanes, and leuk were reduced as compared with nontreatment studies. Cyclo inhibition also attenuated cardiovascular collapse and mediator release in AS, but the other treatments showed no effects. CONCLUSION: H1 receptor blockade and cyclo may attenuate cardiovascular shock in AS. These agents inhibit autacoid release from mast cells in addition to any specific receptor blocking and pathway inhibition effects.

Analysis of Variance↗
PubMed1999

Histamine H3 receptor blockade improves cardiac function in canine anaphylaxis.

In anaphylactic shock (AS), the relative effects of the autacoids including histamine, prostaglandins, and leukotrienes on causing cardiovascular collapse and the extent to which receptor blocking agents and pathway inhibitors may prevent this collapse are not clear. In a ragweed model of anaphylaxis, we examined whether pretreatment with H1, H2, H3 receptor blockers, and cyclooxygenase and leukotriene pathway inhibitors was useful in preventing the depression in left ventricular (LV) contractility known to occur in this model. The dose of allergen was varied to produce similar degrees of shock between treatments. The animals were studied under pentobarbital anesthesia in which the treatment studies were approximately 3 wk apart. LV volumes were measured by sonomicrometric techniques. During challenge, mean arterial blood pressure (Pa), cardiac output (Q), and LV end-diastolic pressure (LVEDP) decreased approximately 50% compared with preshock values in all treatments. Histamine H3 receptor blockade was associated with higher heart rates (HR) and higher stroke work (SW) (p < 0.05) as compared with the other treatment studies. We conclude that histamine H3 activation by inhibiting adrenergic neural norepinephrine release contributes to cardiovascular collapse in AS.

Anaphylaxis↗
PubMed1996

Ready. Set. Wait!

Explore the source record for details and available documents.

Cost-Benefit Analysis↗
PubMed1991

Timing and interpretation of the hemodynamic effects of the pneumatic antishock garment.

STUDY OBJECTIVES: To clarify apparently conflicting reports on the hemodynamic effects of the pneumatic antishock garment (PASG). DESIGN: Ten anesthetized dogs with hemorrhagic hypotension had hemodynamics measured without PASG inflation (group 1) and were compared with ten dogs with PASG inflation (group 2). MEASUREMENTS AND MAIN RESULTS: Baseline and immediate posthemorrhage data were similar in both groups. Group 1 maintained a carotid artery pressure of 85 +/- 9 mm Hg while group 2, by design, maintained baseline CP at 119 +/- 12 mm Hg. After PASG inflation, carotid artery flow increased by 50%, and femoral artery flow decreased tenfold. There was an immediate but transient increase (2.4 +/- 0.1 to 2.7 +/- 0.1 L/min, P less than .05) and a later decrease in cardiac output to 1.9 +/- 0.9 L/min and an increased pulmonary artery wedge pressure and central venous pressure over one hour. Saline (342 +/- 12 mL) reversed the decreased cardiac output without changing pulmonary artery wedge pressure or central venous pressure. CONCLUSION: PASG inflation, therefore, not only increases venous return and cardiac output initially by compressive venous emptying but also decreases venous return and cardiac output later by further venous compression without cardiac decompensation. Thus, apparently conflicting data are explained by the timing and interpretation of the raw hemodynamic measurements.

Animals↗
PubMed1991

Pneumatic antishock garment decreases hemorrhage and mortality from splenic injury.

The effect of the pneumatic antishock garment (PASG) in controlling hemorrhage and death from splenic injury was studied in a canine model. Twelve (two groups of 6) anesthetized dogs had their spleens crushed. Carotid blood pressure, carotid blood flow, splenic artery flow and abdominal aortic flow, as well as the death rate and blood loss, were measured. Group 1 dogs did not have PASG inflation, but group 2 dogs had PASG inflation to an intraperitoneal pressure of 60 mm Hg. All group 1 dogs died within 27 to 58 minutes, but all group 2 dogs survived. Blood loss was 9.4 +/- 1.4 mL/min in group 1 and 1.6 +/- 0.9 mL/min in group 2. In group 1 carotid artery blood pressure, carotid artery flow, splenic artery flow and abdominal aortic flow fell from 120 +/- 10 mm Hg, 284 +/- 12 mL/min, 194 +/- 18 mL/min and 285 +/- 10 mL/min respectively to 0 with death of the animals. By 2 hours in group 2 dogs the carotid artery blood pressure had dropped from 116 +/- 12 to 99 +/- 12 mm Hg, and over the same period carotid artery flow, splenic artery flow and abdominal aortic flow fell from 296 +/- 8 mL/min, 190 +/- 26 mL/min and 279 +/- 16 mL/min respectively to 259 +/- 14 mL/min, 39.0 +/- 6 mL/min and 45 +/- 11 mL/min respectively. Thus, inflation of the PASG maintained carotid artery blood pressure wh ile decreasing splenic, abdominal and aortic flow as well as splenic hemorrhage, with a decrease in the death rate, over a 2-hour period.

Abdomen↗
PubMed1987

Effect of bumetanide in capillary permeability pulmonary oedema.

UNLABELLED: To determine if bumetanide, like furosemide, improves shunt through pulmonary vasoactivity, 20 dogs with unilobar oleic acid pulmonary oedema were studied. Fractional perfusion and intrapulmonary shunt of the oedematous lobe were measured at: baseline, 1 1/2 hours after oleic acid infusion, 15 minutes later after either 0.1 mg X kg-1 of bumetanide in ten dogs (Bumetanide Group) or without bumetanide in ten dogs (Control Group), and 2 1/2 hours after the oleic acid, the bumetanide being administered immediately after the 1 1/2 hours post-oleic acid measurements. Lobar shunts for the Bumetanide Group were: 9.3 +/- 4.0, 54.3 +/- 13.6, 54.7 +/- 13.6, 38.6 +/- 12.0 per cent and for CONTROLS: 8.7 +/- 1.6, 45.1 +/- 8.8, 48.3 +/- 7.8, 70.4 +/- 6.2 per cent. Fractional perfusions of the oedematous lobe were: 29.9 +/- 1, 14.7 +/- 1.1, 14.6 +/- 0.7, 19.3 +/- 1.9 per cent in the Bumetanide Group and 28.6 +/- 2.1, 14.2 +/- 1.1, 14.2 +/- 1.5, and 9.9 +/- 1.1 per cent in CONTROLS. Oedema (wet to body weight ratio) was less (p less than 0.05) in the contralateral lobe (2.5 +/- 0.2 vs. 2.9 +/- 0.3) and the oedematous lobe (4.7 +/- 0.4 vs 6.0 +/- 0.5) after bumetanide-induced diuresis. We conclude that bumetanide decreases shunt by decreasing oedema and not through pulmonary vasoactivity.

Animals↗
PubMed1987

Does indomethacin affect shunt and its response to PEEP in oleic acid pulmonary edema?

We assessed hemodynamics, lobar perfusion, and shunts at base line 1.5 h after unilobar oleic acid edema, 15 min after indomethacin (10 mg/kg iv), and 15 min after positive end-expiratory pressure (PEEP) (10 cm) in 10 dogs. In 10 additional dogs (control) the same measurements were made but no indomethacin was administered. Shunts of the edematous lobe were: 10.6 +/- 6.3, 54.1 +/- 22.8, 30.8 +/- 16.6, and 12.4 +/- 6.3% for dogs administered indomethacin and 10.9 +/- 4.2, 53.8 +/- 13.1, 72.3 +/- 14.6, and 11.5 +/- 4.1% for the controls. Perfusions (% cardiac output) to the edematous lobe were 27.6 +/- 3.6, 14.6 +/- 2.0, 9.9 +/- 1.5, and 27.9 +/- 2.9% in the dogs administered indomethacin and 27.3 +/- 3.1, 14.0 +/- 1.7, 13.2 +/- 1.3, and 26.9 +/- 2.8% in controls. The decrease in lobar perfusion was similar before indomethacin with a further decrease in lobar perfusion and an increase in lobar vascular resistance 15 min after indomethacin. The increase in vascular resistance of the edematous lobe was three times that of nonedematous lobes after indomethacin (149.6 +/- 76% vs. 58.0 +/- 43%). Indomethacin, therefore, decreases shunt possibly by enhancing alveolar hypoxic vasoconstriction and does not block the improvement in shunt with PEEP.

Animals↗
PubMed1987

Decreasing hydrostatic pressure does not uniformly decrease high-pressure pulmonary edema.

Pulmonary artery wedge pressure (PAWP) of 30 mm Hg with left atrial balloon inflation for 1 1/2 hours produced pulmonary edema in eight dogs. PAWP was then decreased to 10 mm Hg for two hours, and shunt, lung water (extravascular thermal volume, or ETV, by thermal dye), and perfusion distribution (radiomicrosphere technique) were measured and compared with four other dogs (group 1) whose PAWP was maintained at 10 mm Hg. The eight dogs with PAWP of 30 mm Hg for 1 1/2 hours were retrospectively subdivided into two groups of four based on ETV (group 2, double baseline ETV; group 3, triple baseline ETV). Baseline ETV and shunt were similar for all groups and remained unchanged for group 1. At 1 1/2 hours, 2 hours (1/2 hour after decreasing PAWP), 2 1/2 hours, and 3 1/2 hours, respectively, ETV were: 13.9 +/- 1.9, 12.8 +/- 2.0, 9.3 +/- 1.5, and 8.5 +/- 1.0 ml/kg in group 2; and 21.9 +/- 2.1, 22.7 +/- 2.2, 22.5 +/- 2.0, and 22.2 +/- 2.0 ml/kg in group 3. A more variable rate of edema formation was detected in eight additional dogs, but failure to resolve higher levels of edema after decreasing PAWP was also demonstrated in this group. Edema was greatest in lower lobes and decreased lobar perfusion. Shunt was higher in group 3 than in group 2 at 1 1/2 hours and decreased in group 2 but not in group 3 at 3 1/2 hours. Changes in colloid osmotic pressure may account for the differences in edema formation and resolution, but our data suggest that, independent of the rate of edema formation, a decrease in vascular exchange surface area at higher levels of edema may inhibit edema resolution when PAWP is decreased.

Animals↗
PubMed1987

Colloid osmotic pressure in pulmonary edema clearance with furosemide.

After tripling of baseline lung water (EVLW), decreasing wedge pressure (PWP) alone for two hours did not decrease EVLW. In 11 of 16 dogs, triple baseline EVLW and a decrease in plasma colloid osmotic pressure (COP) from 21.1 +/- 0.8 to 17.8 +/- 0.8 mm Hg resulted from left atrial balloon inflation at PWP of 28 to 30 mm Hg. With subsequent lowering of PWP to 10 mm Hg, intravenously administered furosemide (1 mg/kg) was given to these 11 dogs. One half hour after furosemide, shunt decreased slightly without decreasing EVLW in all 11 dogs, but by two hours, seven dogs (group 1) decreased EVLW (from 23.2 +/- 1.8 to 11.1 +/- 1.4 ml/kg) and shunt (37.4 +/- 2.0 to 12.9 +/- 2.9 percent), while four dogs (group 2) did not (EVLW: 22.3 +/- 1.4 to 22.5 +/- 0.6 ml/kg: shunt, 36.8 +/- 1.7 to 36.5 +/- 1.9 percent). Group 1 had diuresis, maintained normal blood urea nitrogen and creatinine levels, and increased COP from 17.7 +/- 0.7 to 23.6 +/- 0.5 mm Hg while group 2 was oliguric with elevated BUN and creatinine values and showed no change in COP (17.9 +/- 0.9 to 18.3 +/- 0.6 mm Hg) after furosemide. After decreasing PWP in massive pulmonary edema (triple baseline EVLW), furosemide appeared to enhance edema clearance by changes in COP with diuresis.

Animals↗