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Biomedical subjects

D E Fry

Publications and source records attributed to D E Fry.

At least 91 records · Page 5Linked to original sources
PubMed1987

Serratial bacteremia in the surgical patient.

A 42-month review has identified 32 surgical patients that had 45 episodes of Serratia marcescens bacteremia. Patients were identified in many surgical specialties. The primary focuses of infection were the urinary tract, intravascular devices, sputum, and soft tissue. In five patients, no focus was identifiable. Nine patients had polymicrobial sepsis with other bacteria or Candida. Of 41 isolates studied, five were resistant to all antibiotics that were commercially available. Only 76 per cent were sensitive to amikacin, 63 per cent to gentamicin, and 46 per cent to tobramycin. Statistically fewer patients died when an aminoglycoside and an expanded-spectrum penicillin were used in combination. The 44 per cent mortality rate of this group of patients indicates that environmental control, behavioral modification of health care professionals, and a more rationale use of broad-spectrum antibiotics are necessary to prevent this morbid complication.

Aged↗
PubMed1987

Complement activation in peritonitis. Association with hepatic and renal perfusion abnormalities. First place winner: Conrad Jobst award.

The authors have shown that systemic activation of the complement system with either zymosan or cobra venom factor produces some of the hemodynamic changes characteristic of sepsis, specifically, a reduction in hepatic perfusion despite a normal or hyperdynamic systemic circulation. This study was undertaken to determine whether complement activation accompanied reductions in effective hepatic and renal blood flow (EHBF and ERBF, respectively) in a septic murine model previously demonstrated to be associated with flow redistribution. Rats underwent either cecal ligation and puncture (CLP) or sham laparotomy after a baseline blood sample was collected for complement assay. Eighteen hours later, thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, EHBF by galactose clearance, and ERBF by p-aminohippurate (PAH) clearance were determined. A second blood sample was collected for measurement of total hemolytic complement (CH50) by immune hemolysis of sheep erythrocytes and was compared to the t = 0 sample for calculation of per cent change in CH50. The cardiac output and hematocrit were normal in the CLP group relative to sham. The septic animals were tachycardic and slightly hypotensive, suggesting a diminished systemic vascular resistance. EHBF and ERBF fell dramatically in the septic group despite the normal cardiac output. Residual hemolytic complement activity was reduced to less than 40% of preseptic levels in the CLP group while sham values were no different than baseline, indicating massive complement activation in the septic animals. This study demonstrates an association between complement activation and hepatic and renal perfusion abnormalities in murine peritonitis. Work is underway to establish the temporal relationship between complement activation and visceral flow changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Imidazole and indomethacin improve hepatic perfusion in sepsis.

Visceral microcirculatory insufficiency has been demonstrated in sepsis despite a hyperdynamic systemic circulation. This study examines the effect of the cyclo-oxygenase inhibitor indomethacin and the thromboxane synthetase inhibitor imidazole on septic hemodynamics and visceral perfusion in a septic rat model of cecal ligation and puncture. Animals received either indomethacin (INDO), imidazole (IMID), or saline intramuscularly at t = 0, 6, and 12 hr of peritonitis. Thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, effective hepatic blood flow, effective renal plasma flow, and arterial and mixed venous blood gases were determined at 15 hr. Both INDO and IMID improved effective hepatic blood flow in the septic animals to virtually sham, nonseptic levels without significantly altering systemic hemodynamics. This study suggests that the reduction in hepatic perfusion in sepsis may be mediated by thromboxane, the synthesis of which is suppressed by both INDO and IMID.

Animals↗
PubMed1987

Effect of hemorrhagic shock on oxidative phosphorylation and blood flow in rabbit gastrointestinal mucosa.

The pathophysiologic mechanism responsible for ulceration of gastric fundus and corpus mucosa following hemorrhagic shock is not well defined. We examined the effect of hemorrhagic shock (25 ml blood/kg) and resuscitation (reinfusion of shed blood) on oxidative phosphorylation in different tissues of the rabbit to determine if differences in mitochondrial response to hemorrhagic shock and resuscitation contribute to the propensity of gastric fundus and corpus to necrose before other tissues. Blood flow was measured by using radioisotope-labeled microspheres to determine if changes in regional blood flow could be correlated with this propensity to ulcerate. The respiratory control index (RCI), an index of the integrity of mitochondrial function, was significantly increased in gastric antrum, liver, and kidney from the animals subjected to hemorrhagic shock and successful resuscitation when compared to control animals. In liver and kidney, these differences were largely due to increases in state 3 respirations. Duodenal and gastric corpus and fundus mitochondria showed no differences in RCI between bled and control groups. Blood flow data did not implicate ischemia as the mechanism responsible for the differential rate of ulceration after hemorrhage. The inability of fundus, corpus, and small-bowel mucosal mitochondria to respond to the stress of hemorrhagic shock and resuscitation in a manner similar to liver, kidney, and gastric antral mitochondria may place these tissues at greater risk to ulcerate. Further work is necessary to define whether this difference in mitochondrial response patterns represents a real increase in the maximal respiratory capacity of liver, kidney, and antrum after shock and resuscitation.

Animals↗
PubMed1987

Low-dose dopamine improves effective hepatic blood flow in murine peritonitis.

Diminished effective hepatic blood flow (EHBF) has been postulated as contributory to hepatocellular dysfunction in sepsis. In addition, dopamine has been demonstrated to increase perfusion to selective viscera. In order to examine the effects of peritonitis upon hepatic perfusion and its response to dopamine infusion, peritonitis was induced in rats via cecal ligation and perforation (CLP). Sixteen to 20 hours following insult, cardiac outputs were determined by thermodilution, and effective hepatic blood flow was determined by low-dose galactose clearance. Studies were performed in peritonitis-induced rats (CLP) and sham-operated controls with and without dopamine infusion for 30 minutes (0.5 microgram/100 g/min). Peritonitis resulted in a significant reduction in effective hepatic blood flow (p less than 0.01) despite a maintained cardiac output. Low-dose dopamine infusion resulted in a significant restoration of effective hepatic blood flow in CLP rats without altering cardiac output or hemodynamic status significantly. Dopamine may be beneficial in the maintenance of effective hepatic perfusion in peritonitis.

Animals↗
PubMed1986

Serum kinetics of intraperitoneal moxalactam.

Continuous intraperitoneal administration of antibiotics has been recommended as treatment for peritonitis. The necessity of simultaneous systemic administration of antibiotics remains undefined but usually is performed. Moxalactam kinetics in serum were studied in dogs receiving 15 mg/kg intravenously; 15 mg/kg intraperitoneally; 5 mg/kg hourly with peritoneal lavage; 15 mg/kg intravenously followed by 5 mg/kg hourly intraperitoneally; 15 mg/kg intraperitoneally after 24 hours of peritonitis; and 5 mg/kg hourly by peritoneal lavage after 24 hours of peritonitis. Intraperitoneally administered moxalactam resulted in sustained serum levels compared with intravenously administered drugs. Repeated exchanges in lavage fluid resulted in progressively higher serum levels with each exchange. Peritonitis results in statistically higher levels of serum antibiotic concentration when compared with controls. Continuous intraperitoneal lavage with antibiotics would not appear to require concomitant systemic drug therapy.

Absorption↗
PubMed1986

Mitochondrial and myocardial performance. Response to ischemia and reperfusion.

The relationships between cardiac bioenergy metabolism and myocardial function were examined in a model of global myocardial ischemia and reperfusion. The respiratory activity of distinct populations of subsarcolemmal and interfibrillar mitochondria was correlated with max dP/dt (an index of myocardial contractility with respect to time). Max dP/dt was significantly reduced to 27% of the preischemic value following two hours of cardioplegia-protected, warm, global, ischemia in dogs during the cardiopulmonary bypass period. Reperfusion resulted in improved myocardial function such that by 60 minutes of reperfusion, max dP/dt returned to baseline. Significant declines in both state 3 respiratory rates and respiratory control indexes for subsarcolemmal and interfibrillar mitochondria were noted following the ischemic interval. Mitochondrial function similarly returned to baseline values following 60 minutes of reperfusion. These data demonstrate a close association between mitochondrial and myocardial activity.

Animals↗
PubMed1986

Third generation cephalosporin antibiotics in surgical practice.

The new third generation cephalosporins have a significantly greater spectrum of action against gram-negative bacteria likely to be encountered in surgical infections. This expanded spectrum may permit these drugs to be used in place of combination therapy in patients with polymicrobial infections; however, current evidence does not indicate superior results with these agents over earlier generation choices for surgical prophylaxis. The toxicity profile of these drugs warrants close monitoring for serious complications.

Bacteria↗
PubMed1986

Subpopulations of human heart mitochondria.

Anatomically and biochemically distinct populations of cardiac mitochondria have been isolated from a number of animal species. The physiologic differences between subsarcolemmal (SS) and interfibrillar (IF) mitochondria, coupled with their different location within the cytomatrix, have led to speculation about possible specificities of function within the myocardial cell. To date, these two mitochondrial subpopulations have not been demonstrated in human cardiac tissue. Subsarcolemmal and interfibrillar cardiac mitochondria were isolated from papillary muscle removed from five patients undergoing mitral valve replacement surgery. Mitochondrial respiratory activity was determined polarographically. IF mitochondria had significantly higher state 3 (ADP-dependent) rates of respiration then SS mitochondria (116.7 +/- 7.1 versus 86.5 +/- 8.3 ng atoms or oxygen per minute per milligram mitochondrial protein; P less than 0.05 [mean +/- SE]). These data agree with similar studies performed in other animal species and support the concept of distinct subpopulations of mitochondria within the human myocardial cell.

Adenosine Diphosphate↗
PubMed1986

Alterations of hepatic mitochondrial function in a model of peritonitis in immature rats.

Severe intra-abdominal infection results in significant metabolic dysfunction, multiple systems failure, and mortality. Although the course of peritonitis is particularly rapid and severe in neonates and small children, its physiologic consequences have been poorly studied in these age groups. In order to assess hepatic mitochondrial integrity in a model of fulminant peritonitis in immature animals, the following study was undertaken. Thirty-three immature Sprague-Dawley rats (21 to 28 days of age) and 32 mature rats (weight greater than 250 g) were anesthetized and laparotomies performed. The animals received either cecal ligation and gross perforation (CLP) or cecal manipulation alone (sham). Animals were killed at 2 and 4 hours and livers removed. Mitochondria were isolated by differential centrifugation. Mitochondrial respirations were studied polarographically with glutamate and succinate as substrates in the presence (state 3) and absence (state 4) of adenosine diphosphate (ADP). The Respiratory Control Index (RCI) is the ratio of state 3 to state 4 respiration and is a sensitive indicator of mitochondrial coupling. Results revealed that in mature animals, peritonitis produced a significant increase in RCI with glutamate as substrate (5.2 +/- 0.2) by 4 hours duration as compared with sham operated rats (4.3 +/- 0.1, P less than 0.01). Succinate as substrate revealed no significant alteration in mitochondrial coupling in mature rat hepatic mitochondria in animals subjected to peritonitis. By contrast, peritonitis in immature animals produced a significantly decreased RCI (3.6 +/- 0.2) with glutamate as substrate as compared with sham operated animals (4.8 +/- 0.2, P less than 0.01) by two hours duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1986

Infectious morbidity in extremity fractures.

To review infectious morbidity in extremity fractures, 265 patients with 280 open fractures and 573 patients with closed fractures requiring open reduction and internal fixation (ORIF) were reviewed. Among open fractures, 32 (11%) became infected. Significantly fewer infections occurred in open fractures secondary to gunshot wounds (p less than 0.01) and in the upper extremity regardless of cause (p less than 0.05). Preventive preoperative antibiotics did not appear to affect infection rates. Open fracture infections were consistently with hospital-acquired organisms, and these were consistently resistant to the preventive antibiotic employed. Closed fractures had only 18 (3%) infections after ORIF. Preoperative antibiotics did reduce infection rates compared to rates in patients with no preoperative systemic antibiotics (p less than 0.05). Pathogens in ORIF patients showed a greater preponderance of Staphylococci. In conclusion, preventive antibiotics were only effective in the prevention of infection in the ORIF patients. Open fracture patients consistently develop infections with hospital-acquired pathogens, suggesting that contamination after hospitalization rather than at the time of injury is a major factor.

Anti-Bacterial Agents↗
PubMed1986

Mobile phase optimisation in the separation of antiepileptic drugs by high-performance liquid chromatography.

A simple method is described for adjusting the mobile phase composition to obtain optimum separation of commonly prescribed antiepileptic drugs by high-performance liquid chromatography. The drugs are separated, in less than 6 min, on a column of Hypersil ODS 5 microns (100 mm X 5 mm i.d.) with a high mobile phase flow rate. The final mobile phase composition is a mixture of methanol, acetonitrile, tetrahydrofuran and water, adjusted to give the best separation with our laboratory conditions. The method is described and evidence of precision and accuracy presented. The improved separation resolves the major metabolites of carbamazepine which have been ignored in most methods for antiepileptic drugs. The advantages of mobile phase optimisation to improve the separation of antiepileptic drugs are discussed.

Anticonvulsants↗
PubMed1986

Isovolemic hemodilution: correlations of mitochondrial and myocardial performance.

Subsarcolemmal (SS) and interfibrillar (IF) cardiac mitochondrial respiratory activities were examined under conditions of isovolemic hemodilution in rats. Experimental animals (mean Hct, 21%) had significantly higher cardiac indices than controls (mean Hct, 41.5%) 18 hours following isovolemic hemodilution with 0.9% NaCl. A 40% increase in cardiac output was associated with a significant increase in the respiratory control index (RCI) of the IF mitochondria. This increase in IF RCI occurred as a result of a significant decline in the ADP-independent (State 4) respiratory rate. These data demonstrate the ability of cardiac mitochondria to respond to increased myocardial demand by increasing mitochondrial efficiency and support the concept of subspecialized populations of mitochondria within the myocardial cell.

Animals↗
PubMed1986

Effective organ blood flow and bioenergy status in murine peritonitis.

Whether organ dysfunction frequently encountered in overwhelming bacterial sepsis is a result of a direct cellular "toxic" effect or diminished cellular perfusion remains controversial. To assess the effects of peritonitis on cellular energy status and visceral blood flow, peritonitis was induced in rats by means of cecal ligation and perforation. Five, 10, or 20 hours after cecal ligation and perforation, cardiac outputs were determined by thermodilution, effective hepatic blood flow was determined by low-dose galactose clearance, and effective renal plasma flow was determined by paraminohippuric acid clearance. In similar groups of rats with peritonitis or sham controls, tissue samples of liver, kidney, and skeletal muscle were obtained by freeze-clamp technique for analysis of adenine nucleotides, energy charge, pyruvate, lactate, and pyruvate/lactate ratios (P/L). Despite an increase in cardiac output (p less than 0.05), results indicated in this model that effective hepatic blood flow and effective renal plasma flow were significantly reduced (p less than 0.05). The energy charge and P/L ratios of hepatic (p less than 0.01) and renal (p less than 0.05) tissues were also decreased. In contrast, skeletal muscle energy charge and P/L ratio were unchanged by 20 hours duration. These data support the hypothesis of diminished visceral perfusion as contributory to the cellular dysfunction observed in sepsis. Skeletal muscle appears either nonischemic or more tolerant of ischemia in sepsis.

Adenosine Triphosphate↗
PubMed1986

Experimental bacteremia and hepatic nutrient blood flow.

To study altered hepatic nutrient blood flow during the early phases of bacteremia, Sprague-Dawley rats (250-350 gm) underwent carotid cannulation; 24 hr later, they received an intravascular infusion of 2.5 X 10(8) Escherichia coli (LD70) over 45 min. Controls were anesthetized and cannulated only. Experimental and control animals then received a flow-dependent dose of indocyanine green (5 mg/kg) via the cannula, and arterial blood was sampled at 3, 4, 5, 6, 7, and 8 min after. Separate groups of animals were studied at 3 and 6 hr after bacteremia. The half-life (t1/2) of indocyanine green clearance was then determined at each time period, with t1/2 representing an estimation of total hepatic nutrient blood flow. Results indicated a prolonged t1/2 at both time periods in the bacteremic rats. Hepatic histology from plastic-embedded sections appeared to reveal fibrin, platelets, and leukocyte fragments within the sinusoids. From these data, we conclude that reduced nutrient blood flow occurs during experimental bacteremia prior to systemic changes of arterial pressure.

Animals↗
PubMed1986

Effective renal blood flow and renal energy charge in murine peritonitis.

The temporal sequence of physiological derangements preceding acute renal failure (ARF) observed in overwhelming bacterial septicemia remains controversial. In order to examine the relationship of renal circulatory alterations and cellular dysfunction in murine sepsis, effective renal plasma flow (ERPF), renal tissue metabolites, and energy charge ratios were determined in Sprague-Dawley rats at 10 and 20 hours following induction of peritonitis by cecal ligation and perforation (CLP) or cecal manipulation alone (sham). Tissue levels of adenine nucleotides, lactate, and pyruvate were assayed after freeze-clamping kidneys unilaterally followed by enzymatic determinations. Cardiac outputs were determined by thermodilution and ERPF by p-aminohippuric acid (PAH) clearance. Results indicate in this model, despite an increase in cardiac output (P less than 0.05), ERPF was significantly decreased at both 10 hours (P less than; 0.05) and 20 hours (P less than 0.01) following induction of peritonitis. Further, although tissue pyruvate/lactate ratios showed significant decreases by 10 hours (P less than 0.05), diminished energy charge ratios were not observed until 20 hours following septic insult. These findings support the hypothesis of diminished renal perfusion as contributory and antecedent to cellular dysfunction in septicemic ARF.

Adenine Nucleotides↗
PubMed1985

Experimental myocardial ischemia. Differential injury of mitochondrial subpopulations.

Distinct populations of subsarcolemmal (SS) and inter-fibrillar (IF) rat cardiac mitochondria were studied following 15 and 30 minutes of warm and cold global ischemia. The respiratory control index, state 3, state 4, adenosine diphosphate-oxygen ratio, and specific enzyme activities of these mitochondrial populations were examined. The subsarcolemmar and IF mitochondria were both severely uncoupled and inhibited by warm ischemia. However, IF mitochondria had a higher RCI at each ischemic interval. In cold ischemia, IF mitochondria were not injured compared with control specimens. Subsarcolemmar mitochondria showed a trend towards a lower RCI that was statistically significant at 30 minutes with succinate as a substrate. These data implicate a differential injury of ischemia on the compartmentalized bioenergy metabolism of the myocardial cell.

Animals↗