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Biomedical subjects

D L Bredle

Publications and source records attributed to D L Bredle.

At least 37 records · Page 2Linked to original sources
PubMed1995

The treatment of palmar and plantar warts using natural alpha interferon and a needleless injector.

BACKGROUND: The treatment of palmar and plantar warts is difficult and often frustrating. The need for multiple destructive treatments and recurrences after apparent cure are common. OBJECTIVE: The purpose of this study was to determine if intralesional natural alpha interferon might offer an effective alternative therapy for common plantar and palmar warts. METHODS: A series of 22 private office patients with palmar and plantar warts were treated with intralesional natural alpha interferon using a needless injector. We treated twice weekly for a minimum of 8 weeks or until clear. RESULTS: Sixteen patients (73%) showed complete clearing of their warts in a mean of 11 weeks of twice weekly treatment. Upon follow-up, which averaged 9.5 months, 17 of 21 patients (81%) remained clear of their warts. CONCLUSION: Natural alpha interferon by needless injector appears to represent an effective alternative treatment for palmar and plantar human papillomavirus lesions. Further study of this modality is indicated.

Adolescent↗
PubMed1995

N-acetylcysteine preserves oxygen consumption and gastric mucosal pH during hyperoxic ventilation.

Hyperoxic ventilation, used to prevent hypoxemia during potential periods of hypoventilation, has been reported to paradoxically decrease whole body oxygen consumption (VO2). Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism. We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine (NAC) would preserve whole body VO2 and prevent deterioration of oxygenation in gastric mucosal tissue during hyperoxia. Thirty-eight patients, requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to sepsis syndrome, were included in this randomized experiment. All patients exhibited stable clinical conditions (hemodynamics, body temperature, hemoglobin, FIO2 < 0.5). A gastric tonometer was placed to measure the gastric intramucosal pH (pHi), which indirectly assesses nutritive blood flow to the mucosa. Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick. After baseline measurements, patients randomly received either 150 mg.kg-1 NAC (n = 19) or placebo (n = 19) in 250 ml 5% dextrose intravenously over a period of 15 min. Measurements were repeated 30 min after starting NAC or placebo infusion, 30 min after starting hyperoxia (FIO2 = 1.0), and 60 min after resetting the original FIO2. There were no significant differences between groups in any of the measurements before treatment and after the return to baseline FIO2 at the end of the study. NAC, but not placebo infusion, caused a slight but significant increase in cardiac output and decrease in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1995

Randomized comparison of gastric pH control with intermittent and continuous intravenous infusion of famotidine in ICU patients.

OBJECTIVE: To compare gastric pH control using intravenous famotidine as a primed, continuous infusion versus intermittent infusion. METHODS: In a prospective, double-blind study, 40 ICU patients at risk for stress ulceration were randomly assigned to receive either famotidine 20 mg intravenous bolus followed by 1.67 mg/h infusion or famotidine 20 mg intravenously every 12 h. Intraluminal gastric pH was recorded at baseline and every 4 h using a glass electrode. Clinical outcome indicators were also monitored. Subjects were studied for a minimum of 24 h and a maximum of 6 days. Continuous variables were analyzed by ANOVA and nominal variables by Fisher's exact test (alpha = 0.05). RESULTS: Nineteen patients were randomized to the continuous infusion group, and 21 were randomized to the intermittent group. Using gastric pH greater than 4.0 as an endpoint, the continuous group exhibited better pH control, both in terms of percentage of total measurements (83% versus 63%, p < 0.001) and time spent above pH 4.0 (91% versus 76%, p < 0.01). Similar results were found at pH greater than 5.0 (78% versus 56% for all measurements for the continuous and bolus groups, respectively (p < 0.001), and 88% versus 72% for the time spent above pH 5.0 (p < 0.01). Clinical outcomes, including evidence for gastrointestinal bleeding and hospital mortality, did not differ significantly between groups. CONCLUSION: Famotidine infusion at 1.67 mg/h, when preceded by a bolus dose of 20 mg, provides a greater and more sustained increase in gastric pH than intermittent administration of famotidine 20 mg every 12 h.

Aged↗
PubMed1994

Name that tone. The proliferation of alarms in the intensive care unit.

The proliferation of alarms on equipment in ICUs contributes to a level of noise that can disturb both patient and staff. To determine whether these alarms are identifiable by sound alone to our ICU staff, we recorded 33 audio signals commonly heard on the ward, 10 of which we defined as critical alarms. One hundred subjects (25 physicians, 41 nurses, and 34 respiratory therapists) listened individually in a quiet room to the tape recording that consisted of 10 s of audible followed by a 10-s pause for a written response. Only 50 percent of the critical alarms and only 40 percent of the noncritical sounds were correctly identified. By occupation, registered respiratory therapists scored highest, followed by nurses, nonregistered therapists, and physicians. Those with > 1 year ICU work experience scored higher than those with less than 1 year. We conclude that the myriad of alarms that regularly occur in the ICU are too much for even experienced ICU staff to quickly discern. Patient and caregiver alike could benefit by a graded system in which only urgent problems have audible alarms, and these should be covered by regular in-service training.

Auditory Perception↗
PubMed1994

Prostacyclin in septic shock.

OBJECTIVE: Investigation of the hypothesis that the infusion of 10 ng/kg/min prostacyclin (epoprostenol) (PGI2) improves O2 uptake in patients with hyperdynamic septic shock. DESIGN: Prospective, single cohort design. SETTING: ICU, university hospital. PATIENTS: Fifteen postoperative patients with septic shock. INTERVENTIONS: Infusion of 10 ng/kg/min of PGI2 for 60 min. MEASUREMENTS: Complete hemodynamic profile with O2 transport-related variables (simultaneous measurements of VO2 from the respiratory gases and by cardiovascular Fick) and blood lactate levels before start of the PGI2-infusion and 60 min thereafter. MAIN RESULTS: Oxygen delivery increased significantly (14 percent) from its already high value, 750 +/- 238 to 852 +/- 214 ml/min/m2. The O2 extraction ratio remained unchanged. When VO2 was measured from the respiratory gases, it was unchanged. When VO2 was measured by cardiovascular Fick, it increased slightly (p < 0.05). CONCLUSIONS: We conclude that in this O2 challenge test with PGI2 in patients with septic shock, an increase in O2 delivery was not matched by an increase in VO2. We believe that the adequate conventional support of these patients may have prevented the PGI2 from revealing a "covert" O2 debt. The PGI2 test did not predict mortality by O2 supply dependency. The small increase in VO2 as calculated indirectly suggests a degree of mathematical coupling of O2 delivery and uptake.

Adult↗
PubMed1994

Influence of N-acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double-blind study.

OBJECTIVES: Deactivation of endothelium-derived relaxing factor due to an increased oxygen radical load during sepsis may contribute to an impairment in microcirculatory blood flow. We investigated whether treatment with the sulfhydryl donor and oxygen radical scavenger, N-acetylcysteine, would improve whole-body oxygen consumption (VO2), gastric intramucosal pH, and veno-arterial CO2 gradient (veno-arterial PCO2) during septic shock. DESIGN: Prospective, randomized, double-blind study conducted over 2 yrs. SETTING: Septic shock patients admitted to the intensive care unit. PATIENTS: Fifty-eight patients requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to septic shock, were included in this study. All patients were examined within 72 hrs after the onset of sepsis. They were optimally resuscitated by conventional means with volume and inotropic agents, and exhibited stable clinical conditions (hemodynamic values, body temperature, hemoglobin, FIO2). INTERVENTIONS: A gastric tonometer was inserted to measure the gastric intramucosal pH. Subjects randomly received either 150 mg/kg of intravenous N-acetylcysteine or placebo over a 15-min period, then a continuous infusion of 12.5 mg/hr of N-acetylcysteine or placebo over approximately 90 mins. MEASUREMENTS: Infusion measurements were begun 60 mins after the beginning of infusion and lasted approximately 30 mins. The infusion was then discontinued and 2 hrs later the final measurements were taken. MAIN RESULTS: Basic patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation [APACHE] II scores, Multiple Organ Failure scores) did not differ significantly, nor did pre- and 2-hr postinfusion measurements differ between any of the groups. Thirteen (45%) patients responded (i.e., showed an increase in VO2 > 10%, reaching a mean of 19%) to the N-acetylcysteine infusion. The N-acetylcysteine responders also showed an increase in gastric intramucosal pH, a decrease in veno-arterial PCO2, an increase in oxygen delivery, cardiac index, stroke index, and left ventricular stroke work index, as well as a significant decrease in systemic vascular resistance in comparison to baseline. The N-acetylcysteine nonresponders, as well as the patients in the placebo group, did not show any significant changes in any of these variables. The N-acetylcysteine responders had a higher survival rate (69%) than the non-responders (19%) and were studied earlier after onset of sepsis (37 hrs) than the nonresponders (61 hrs). The only significant difference between the entire N-acetylcysteine group (which included responders plus nonresponders) and the placebo group was an increased VO2 in the entire N-acetylcysteine group during infusion measurements. CONCLUSIONS: N-acetylcysteine provided a transient improvement in tissue oxygenation in about half of the septic shock patients, as indicated by an increase in VO2 and gastric intramucosal pH and a decrease in veno-arterial PCO2. The higher survival rate in the N-acetylcysteine responders and the fact that half of the patients receiving N-acetylcysteine did not respond, suggests that, in some patients, sepsis irreversibly damages the microvasculature to the extent that N-acetylcysteine has no effect. If analyzed by intention to treat, the N-acetylcysteine did not produce effects that were significantly different from the placebo. Whether the N-acetylcysteine challenge was merely diagnostic or whether N-acetylcysteine can be effective in the treatment of sepsis deserves further investigation.

Acetylcysteine↗
PubMed1991

Systemic and muscle oxygen uptake/delivery after dopexamine infusion in endotoxic dogs.

BACKGROUND AND METHODS: This study was designed to test whether dopexamine, a dopaminergic and beta 2-adrenergic agonist, would a) increase systemic oxygen delivery (DO2) in endotoxic dogs, and b) interfere with the ability of resting skeletal muscle to extract oxygen. There were three treatment groups (n = 6 in each group): control, endotoxin alone (E) 4 mg/kg iv, and endotoxin + dopexamine (E + D) 12 micrograms/kg.min. Data were analyzed between and within groups by split-plot analysis of variance with significance of identified differences tested post hoc by Duncan's multiple range test. Donor RBC and dextran were used after endotoxin to maintain adequate perfusion pressures, with Hct kept near 40%. Blood flow to left hindlimb muscles was decreased in controlled steps of 15 min each after stabilization. RESULTS: In E group, cardiac output (Qt), mean arterial pressure (MAP), systemic DO2, and oxygen uptake (VO2) decreased despite blood volume expansion. In E + D group with similar volume expansion, dopexamine maintained Qt, systemic DO2, and VO2 near the control levels, although MAP and systemic vascular resistance were reduced. In comparison with control subjects, endotoxin increased critical DO2 in the isolated limb muscles from 4.6 to 7. mL/kg.min and decreased critical oxygen extraction from 81% to 68%. The pressure/flow relationship in the limb became flattened, indicating loss of vascular reactivity. In the E + D group, there was no further change in the pressure/flow curve nor in the critical oxygen extraction level. CONCLUSIONS: Dopexamine provided hemodynamic support for endotoxic dogs, thereby increasing total DO2 and VO2, while not altering oxygen extraction in the muscle.

Adrenergic Agonists↗
PubMed1990

Actions of a dopaminergic and beta 2-adrenergic agonist on O2 extraction by canine skeletal muscle.

We have shown that an unopposed stimulation of beta-vasodilator adrenoceptors can cause a decreased ability of skeletal muscle to extract O2 when O2 delivery was progressively lowered. The significance of this finding with respect to the application of dopexamine to cardiac failure or to any other condition that causes a decrease in peripheral O2 delivery, however, needs to be assessed when an appropriate increase in vasoconstrictor tone is allowed to occur.

Adrenergic beta-Agonists↗
PubMed1990

Angiotensin and alpha-adrenoceptor activation play a role in hemodynamic response to aortic cross-clamping.

This study was designed to identify the possible role of vasoconstricting compounds released from ischemic tissues in the hemodynamic response to cross-clamping of the thoracic aorta. Twenty-one dogs were anesthetized with pentobarbital sodium. The left hindlimb was denervated, vascularly isolated, and pump perfused at a constant rate with blood drained from the inferior vena cava after passing through a gas-exchanging membrane where oxygen and carbon dioxide tensions were maintained within normal limits. Left and right thoracotomies were performed, and the aorta and inferior vena cava were cross-clamped. The cross-clamping was associated with 33-45% increase in limb vascular resistance in denervated control animals (n = 6). In animals pretreated with Enalaprilat (2 mg/kg, n = 6), an angiotensin-converting enzyme inhibitor, limb vascular resistance did not change significantly. In animals pretreated with phenoxybenzamine (3 mg/kg, n = 6), an alpha-adrenoceptor antagonist, limb vascular resistance significantly decreased to 43% of preclamped level. The study demonstrated that vasoconstrictive compounds, such as angiotensin and catecholamines, play a role in systemic hemodynamic changes, including arterial hypertension, observed during cross-clamping of the thoracic aorta.

Angiotensin II↗
PubMed1989

O2 uptake in bled dogs after resuscitation with hypertonic saline or hydroxyethylstarch.

Hemodynamic and metabolic variables were measured for the whole body and isolated hindlimb of anesthetized dogs during resuscitation from hemorrhagic shock, using a small volume of hypertonic saline or a larger volume of hydroxyethylstarch. Twelve dogs were bled and maintained at a mean arterial pressure (MAP) of 40 mmHg for 30 min. Six dogs were then infused with 7.5% NaCl in 5 ml/kg hydroxyethylstarch (HTS group), and six received 6% hydroxyethylstarch alone (HES group) in an amount to approximate the maximum MAP achieved with hypertonic saline. Hypertonic saline replacement was approximately 16% of shed blood volume compared with 66% for hydroxyethylstarch. With hypertonic saline, cardiac output returned to base line, but O2 delivery did not. Hydroxyethylstarch increased cardiac output above base line, and O2 delivery was near base line. O2 uptake with hydroxyethylstarch peaked at 40% above control at 10 min of resuscitation. Excess O2 uptake in recovery was higher than O2 deficit in hemorrhage with the HES group but not with the HTS group. In the isolated hindlimb, vascular resistance decreased rapidly on hypertonic saline infusion but reached similar levels at 10 min of resuscitation with both fluids. With progressive lowering of blood flow to the pump-perfused hindlimb, ability of limb muscle to extract O2 was the same for the HTS and HES groups. With hemodilution by volume replacement with acellular fluid after hemorrhage, a seemingly adequate cardiac output and arterial pressure may be underresuscitation if O2 delivery does not meet the increased O2 demand.

Animals↗
PubMed1989

Critical O2 delivery to skeletal muscle at high and low PO2 in endotoxemic dogs.

An ischemic canine limb model was used to determine whether endotoxin reduces the ability of resting skeletal muscle to extract O2 and whether increasing the arterial PO2 would increase its O2 extraction. Isolated limbs were pump perfused via an extracorporeal circuit with membrane oxygenator at three progressively lower flows and PO2 of both 60 and 200 Torr, whereas the rest of the body remained normoxic and normotensive. Six anesthetized, paralyzed dogs were injected with endotoxin (4 mg/kg, ENDO), and another six were controls (CONT). Limb critical O2 delivery was higher (P less than 0.05) in ENDO than CONT (8.3 vs. 6.1 ml.kg-1.min-1). Critical venous PO2 was also higher (P less than 0.05) in ENDO than CONT (38 vs. 30 Torr). Critical O2 extraction ratio was lower (P less than 0.05) in ENDO than CONT (0.60 vs. 0.73). There were no differences in these variables between low and high arterial PO2. We concluded that 1) endotoxin can cause a small but significant O2 extraction defect in skeletal muscle, 2) increasing arterial PO2 did not correct such a defect, nor did it improve O2 uptake in ischemic, but otherwise healthy, muscle, and 3) skeletal muscle may contribute to the peripheral O2 extraction defect in adult respiratory distress syndrome insofar as endotoxin effects model those found in adult respiratory distress syndrome.

Animals↗
PubMed1989

Comparison of central-venous to mixed-venous oxygen saturation during changes in oxygen supply/demand.

Because central venous O2 saturation (superior vena cava, ScvO2) can be monitored with less patient risk than mixed venous O2 saturation (pulmonary artery, SvO2), we examined the correlations between SvO2 and ScvO2 over a broad range of cardiorespiratory conditions, including hypoxia, hemorrhage, and resuscitation in anesthetized dogs. The correlation coefficient (r) between SvO2 and ScvO2 in 179 simultaneously drawn blood samples from 22 dogs was 0.97. In another nine dogs, the two sites were continuously and simultaneously monitored with fiberoptic catheters; r was 0.96 with a mean difference of 3.7 +/- 2.9 percent (SD) saturation. In each dog the changes in ScvO2 closely paralleled the changes in SvO2. Although absolute values of ScvO2 are not sufficiently identical to SvO2 to calculate O2 uptake or pulmonary shunt precisely, close tracking of changes in the two sites across a wide range of hemodynamic conditions warrant further consideration of ScvO2 for patient monitoring of trends in O2 supply/demand.

Animals↗
PubMed1988

Phosphate supplementation, cardiovascular function, and exercise performance in humans.

The use of oral phosphate (Pi) supplements to improve muscular work performance has long been proposed without substantiating data. In a double-blind, crossover experiment 11 male runners ingested calcium Pi (176 mmol/day) or placebo for 4 days. On the 3rd treatment day, subjects ran an incremental maximal aerobic capacity test (VO2 max) on a treadmill, and on the 4th day a treadmill run to exhaustion at approximately 70% VO2max. By the 4th day of Pi loading, plasma Pi was significantly higher than control (P less than 0.05); however, erythrocyte Pi, 2,3-diphosphoglycerate, and O2 half-saturation pressure of hemoglobin (P50) were not elevated. VO2 max was not changed by the treatments (mean 62.9, 64.2, 64.9 ml.kg-1.min-1 for control, Pi, and placebo bouts, respectively) nor was submaximal run time to exhaustion (61.6 min for Pi, 65.5 min for placebo). Stroke volume at steady-state VO2 was decreased with Pi (P less than 0.05), whereas cardiac output tended (P = 0.07) to be lower. Greater arteriovenous O2 difference (P less than 0.05) with Pi suggested a peripheral effect that increased O2 extraction. We concluded that in healthy individuals Pi loading produced no improvement in work tolerance or aerobic capacity but did alter some aspects of cardiovascular function.

2,3-Diphosphoglycerate↗