Search PubMed⌕ Search

Biomedical subjects

D E Fry

Publications and source records attributed to D E Fry.

At least 73 records · Page 4Linked to original sources
PubMed1989

Breast cancer survival and perioperative blood transfusion.

The effect of perioperative blood transfusion on disease-free and overall survival was studied in 812 patients with stages I and II breast cancer, followed up prospectively in a multicenter study. All patients initially underwent a modified radical mastectomy. Patients with axillary node-negative, stage I cancer were followed up without additional therapy. Patients with axillary node-positive, stage II cancer were randomized to receive adjuvant chemoendocrine therapy. Transfusion was done in 35.8% of the patients with stage I and in 37.3% of the patients with stage II cancer. For the patients with stage II cancer, perioperative blood transfusion did not affect disease-free or overall survival. For the patients with stage I cancer, perioperative blood transfusion resulted in a worse disease-free and overall survival (p = 0.05 and 0.02, respectively), which was particularly evident for those patients who received more than 1 unit. This study suggests that stage of disease, adjuvant therapy, number of transfusions, and duration of follow-up must be considered in further analyses.

Actuarial Analysis↗
PubMed1988

Antibiotics in surgery. An overview.

Antibiotic utilization in the surgical patient has the two unique features of preventive use in high-risk procedures and frequent use in suspected or documented polymicrobial infection. These two features have resulted in the search for agents with broader spectrums. Although numerous antibiotics or combinations of antibiotics can be shown to provide comparable results for both preventive and therapeutic indications, no superior choice has been identified in either area. Indeed, the search for broader spectrums of antibiotics may not further improve the identified results. If this is so, newer areas of exploration in antibiotic therapy in the surgical patient will need to focus on optimizing pharmacologic, toxic, and economic features while preserving comparability in clinical outcome.

Animals↗
PubMed1988

Cefotetan: a perspective for the surgical patient.

The data have shown that cefotetan has comparable clinical effectiveness when compared with cefoxitin in surgical prophylaxis and in patients with mild-to-moderate polymicrobial infection. This experience has consistently focused on the longer serum elimination half-life of cefotetan, which allows the antibiotic to be given less often than shorter half-life alternatives. A more extensive experience in seriously ill patients is necessary to further address 1) the use of cefotetan as an alternative to combination antibiotic therapy; 2) the risks of the anaerobic DOT group or enterococcal failure; and 3) potential clinical expression of any bleeding diathesis. The initial clinical experience reported herein appears favorable.

Cefotetan↗
PubMed1988

Systemic complement activation produces hemodynamic changes characteristic of sepsis.

Zymosan was administered intravenously in graded doses to Sprague-Dawley rats to investigate the hemodynamic effects of systemic complement activation. At two hours, thermodilution cardiac output, mean arterial pressure, heart rate, systemic vascular resistance, hematocrit, effective hepatic and renal blood flows, and percent change in total hemolytic complement activity were measured on all animals. Progressively increasing doses of zymosan produced characteristic hemodynamic changes of progressively deteriorating stages of hyperdynamic sepsis. In addition, complement activation resulted in a redistribution of systemic blood flow with hepatic hypoperfusion similar to that seen in sepsis. Renal blood flow was unaffected early after complement activation. Additional rats were studied from the control and a representative zymosan-treated group at 24 and 48 hours to determine if the hemodynamic changes observed at two hours persisted or resolved. All systemic hemodynamic measures returned to normal at both 24 and 48 hours. Liver blood flow, however, remained depressed and actually deteriorated over time. Renal perfusion, which was stable at both two and 24 hours, fell below control values in the zymosan-treated group at 48 hours. We conclude that complement may be a mediator of both systemic and visceral flow abnormalities that precede, and perhaps precipitate, organ failure in trauma and sepsis.

Animals↗
PubMed1988

Femur fracture with associated soft-tissue injury produces hepatic ischemia. Possible cause of hepatic dysfunction.

Clinical studies demonstrate that early débridement and operative fixation of femur fractures in multiply injured patients lowers both the incidence and severity of hepatic failure. Perhaps the single most important determinant of hepatic function is nutrient hepatic perfusion. This study compares systemic and hepatic blood flow in rats that have sustained femur fractures with or without associated soft-tissue injury. Femur fracture without soft-tissue trauma resulted in a hyperdynamic state with normal blood flow distribution at 24 hours after injury and normal hemodynamics at 48 hours. When femur fracture was associated with soft-tissue trauma, the elevated cardiac output at 24 hours was not matched by a proportionately elevated hepatic blood flow. In this latter group, the cardiac output was normal at 48 hours, but the hepatic perfusion defect remained. Retained fracture fragments, hematoma, and injured and necrotic soft tissue may serve as a stimulus leading to a pathologic reduction in hepatic perfusion.

Animals↗
PubMed1988

Effects of muramyl dipeptide and core body temperature on peritoneal bacterial clearance.

To examine the interaction between muramyl dipeptide (MDP) and core body temperature in murine peritonitis, 120 Sprague-Dawley rats were randomized to receive either 0, 1, or 4 micrograms/g body weight of MDP. Twenty-four hours later a sublethal intraperitoneal inoculation of Escherichia coli was given after core body temperature regulation at 32 degrees C to 40 degrees C, which was maintained for 30 minutes. Killing of the rats at 1, 3, or 6 hours later allowed evaluation of peritoneal white blood cell and bacterial counts. Results demonstrated that MDP (independent of core body temperature) caused an increased peritoneal white blood cell response at one and six hours and an increased peritoneal bacterial clearance at three hours. Increasing core body temperature adversely affected peritoneal bacterial clearance. High-dose MDP was clearly significant in acceleration of peritoneal bacterial clearance. No interaction between MDP and core body temperature was seen.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Allopurinol and lodoxamide in complement-induced hepatic ischemia.

Intravascular complement activation with either zymosan or cobra venom factor (CVF) impairs hepatic blood flow. Oxygen radical scavengers given at the time of complement activation attenuate the resulting hepatic ischemia. It is not clear whether complement-stimulated phagocytes or transiently ischemic then reperfused endothelial and parenchymal cells generated the toxic oxygen radicals. In this study, a group of rats were given allopurinol (50 mg/kg/day postoperatively X 3 days plus 100 mg/kg iv at t = 0), a specific inhibitor of xanthine oxidase, prior to complement activation with CVF (20 units/kg iv at t = 30 and 60 min) to determine whether xanthine oxidase-derived oxygen radicals contributed significantly to the hepatic perfusion abnormalities. Additional rats received lodoxamide tromethamine (10 mg/kg iv bolus at t = 0 followed by 20 mg/kg/hr iv infusion), a novel and potent inhibitor of mast cell release and inhibitor of xanthine oxidase, prior to the same CVF challenge to determine whether mast cell mediators were involved in the flow disturbance. Thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, and effective hepatic blood flow (EHBF) by galactose clearance were determined at t = 2 hr. The percentage change in total hemolytic complement activity (% delta CH50) was determined between serum obtained prior to sacrifice and at t = 0. Systemic hemodynamics and HCT were for the most part unaffected regardless of pretreatment group or challenge with CVF or saline. CVF challenge produced a 25% reduction (P less than 0.05) in EHBF in vehicle-pretreated rats compared to saline challenge. Neither allopurinol nor lodoxamide tromethamine significantly improved EHBF when given prior to CVF challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗
PubMed1988

Multiple system organ failure.

Multiple system organ failure represents the final common pathway to a fatal outcome in severely infected patients. Despite the development of extensive support technology, the mortality rate in this group of patients remains high: in excess of 50 per cent. This rate underscores the need for newer treatment modalities. Numerous mediators/effectors appear to play a role in the complex evolution of the process. The independent and interactive effects of these numerous mediators/effectors remain to be elucidated. Future therapies will need to address immunomodulation of the host and biochemical manipulation of the fundamental process before significant improvement in outcome can be expected.

Critical Care↗
PubMed1988

Obstructive jaundice. Causes and surgical interventions.

Biliary obstruction can be caused by a number of conditions and can occur in persons of all ages. In every case, prompt diagnosis affords the best opportunity for surgical therapy. Accurate preoperative diagnosis can be difficult because benign and malignant causes may appear similar radiographically. Options in surgical management can be as simple as extraction of a solitary common duct stone or as extensive as pancreaticoduodenectomy or hepatectomy and liver transplantation. Because of the risk of infection with biliary surgery, prophylactic antibiotic treatment should be considered.

Adenoma, Bile Duct↗
PubMed1988

Contribution of toxic oxygen intermediates to complement-induced reductions in effective hepatic blood flow.

This study examines the effects of complement activation and of complement-induced oxygen radical production on the principal determinant of hepatic function, i.e., effective hepatic blood flow (EHBF). Female Sprague-Dawley rats received cobra venom factor, 40 units/kg, in two divided doses at 30-minute intervals. At t = 2 hours, thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, and EHBF by galactose clearance were determined. Complement activation produced a significant depression in EHBF independent of changes in systemic perfusion. To determine whether oxygen radicals participated in the insult, additional animals were pretreated with superoxide dismutase, 6 mg/kg, plus catalase, 15 mg/kg, immediately before complement activation. Concomitant treatment with the oxygen radical scavengers attenuated the degree of complement-induced hepatic ischemia, again independent of effects on systemic perfusion. This study suggests that the reduction in hepatic blood flow that accompanies animal models of trauma and sepsis may result, in part, from the sequelae of complement activation with oxygen radicals as secondary mediators.

Animals↗
PubMed1988

Visceral perfusion abnormalities following complement activation. Clues to the mediators of organ ischemia in trauma and sepsis. First place winner: Conrad Jobst Award.

Complement, activated during infection and injury, has been implicated as a mediator of microvascular injury and obstruction. This study examines how two potent activators of complement, zymosan, and cobra venom factor (CVF), affect systemic and visceral perfusion. Rats were injected with either saline (1 ml/kg), zymosan (5 mg/kg) or CVF (5 units/kg) at t = 0 and 30 minutes. Thermodilution cardiac output, mean arterial pressure, heart rate, systemic vascular resistance, and hematocrit were determined at t = 2 hours. Effective hepatic and renal blood flows, by clearance of galactose and p-aminohippurate respectively, were determined over the next hour. The per cent change in total hemolytic complement from t = 0 to t = 3 hours was determined by immune hemolysis of sheep erythrocytes. There was no difference in systemic hemodynamic parameters between the three groups. Hepatic blood flow was depressed in both the zymosan (3.83 +/- 0.23 ml/min/100 g) and CVF (3.72 +/- 0.20 ml/min/100 g) groups compared with controls (4.62 +/- 0.19 ml/min/100 g, P less than 0.05). Renal blood flow in the zymosan-treated group (6.40 +/- 0.24 ml/min/100 g) increased over control (4.80 +/- 0.40 ml/min/100 g, P less than 0.05) but was unchanged in the CVF group (5.06 +/- 0.23 ml/min/100 g). The amount of complement activated correlated with the change in hepatic (r = -0.419, P less than 0.05) but not renal (r = -0.008, P = 0.917) flow. Complement activation may occupy a proximal position in the pathogenesis of hepatic ischemia associated with trauma and sepsis.

Animals↗
PubMed1988

Urinary tract infections in the surgical patient.

Urinary tract infection (UTI) continues to be a common nosocomial infection. From a 2-year city-county hospital experience, 212 nosocomial UTI were identified in 153 patients from 3747 admissions. Mean age was 54 years; 102 were men. Foley catheterization was an associated factor in 129 patients (84%). UTI was caused by 40 different species of bacteria. In 28 infections (13%), the UTI was polymicrobial. Only nine patients had bacteremia. The bacteriology of the UTI depended on whether the patient had received systemic antibiotics previously during the hospitalization. Prior antibiotic administration increased the probability of Pseudomonas and Serratia as pathogens. Thus, patients that have had antibiotic therapy demonstrate a distribution of pathogens that are different from patients not receiving antibiotics, and a distribution different from the community-acquired UTI. Continued emphasis on the shorter duration and more judicious use of systemic antibiotics for both prophylaxis and therapy is warranted.

Adolescent↗
PubMed1987

Alterations in renal perfusion and renal energy charge in murine peritonitis.

Whether acute renal failure following overwhelming bacterial septicemia is a initially a consequence primarily of a cytotoxic insult or a perfusion insufficiency remains unclear. To assess the effects of intra-abdominal sepsis on the distribution of renal blood flow and renal cell bioenergy status, the glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and energy-charge ratios were measured in rats following cecal ligation/puncture (CLP) or sham laparotomies. The CLP animals demonstrated a decrease in ERPF of 42% and 58% from sham groups at ten and 20 hours, respectively. The GFR showed similar but more severe impairments of 53% and 71% at ten and 20 hours, respectively, following insult despite moderate increases in cardiac output. The disproportionate decrease in GFR over ERPF supports the hypothesis of a corticomedullary redistribution of renal blood flow in sepsis. Renal energy charge, unchanged at ten hours, decreased significantly at 20 hours. Diminished renal perfusion and the redistribution of renal blood flow precedes and may contribute to the renal cell bioenergy derangements in septic acute renal failure.

Adenine Nucleotides↗
PubMed1987

Galactose elimination kinetics in sepsis. Correlations of hepatic blood blow with function.

To study hepatic blood flow with clearance techniques during sepsis, it is essential to work within the limitations of the test being applied. Based on galactose elimination kinetics, this study validates galactose clearance at low concentrations as an estimate of effective hepatic blood flow in a rat peritonitis model of cecal ligation and puncture. Hepatic function as determined by galactose elimination capacity fell 25% at ten hours after induction of peritonitis, which correlated closely with the 20% reduction in effective hepatic blood flow at the same time point despite a normal cardiac output. The pattern of reduced flow and reduced function is consistent with intrahepatic flow redistribution. Inadequate flow at the microvascular level with secondary cellular injury may explain the liver dysfunction observed during sepsis.

Animals↗
PubMed1987

Hepatic microsomal adenosine triphosphatase and mitochondrial function. Response to cold and warm ischemia.

We investigated the response of mitochondrial function and microsomal adenosine triphosphatase (ATPase) activity in rat liver tissue subjected to in vitro ischemia at either 0 degree C to 4 degrees C or 37 degrees C for 30 to 60 minutes. Mitochondrial coupling, expressed as respiratory control index, was preserved at up to 60 minutes' cold ischemia. However, respiratory control index was decreased significantly from control by 30 minutes of warm ischemia. Both microsomal magnesium-activated ATPase and sodium-potassium ATPase activity were significantly increased by 60 minutes of warm ischemia yet were unaltered by 60 minutes of ischemia at 0 degree C to 4 degrees C. Warm ischemia produces deleterious effects on energy-generating (mitochondria) and energy-utilizing (ATPase) activity. Hypothermia provides a significant prolongation of cellular viability in ischemic tissue in terms of bioenergetic status. In addition to organ procurement and transplantation, hypothermic cytoprotection may prove valuable in areas such as shock, ischemia, and other clinical conditions of compromised visceral perfusion.

Adenosine Triphosphatases↗
PubMed1987

Flow redistribution in a hyperdynamic small animal burn: comparison to patterns in sepsis.

Visceral hypoperfusion with local accumulation of lactate in the ischemic tissues has been reported in a septic rat model despite a hyperdynamic systemic circulation. This visceral ischemia is felt to contribute to the multiple system organ failure (MSOF) syndrome associated with sepsis. The purpose of this study was to determine whether a similar redistribution of blood flow existed in rats after a severe thermal injury as it too is associated with MSOF. Twenty-four hours after animals were subjected to either a resuscitated 50% scald burn (BURN) or sham treatment (SHAM), thermodilution cardiac output (CO), effective hepatic blood flow (EHBF) by galactose clearance at low concentrations, effective renal plasma flow (ERPF) by para-aminohippurate clearance, and blood, liver, and skeletal muscle pyruvate (P), and lactate (L) concentrations were determined. CO increased 52% in BURN (46.5 +/- 2.8 ml/min/100 g, n = 21) versus SHAM (30.7 +/- 1.0 ml/min/100 g, n = 22; P less than 0.001) while EHBF increased only 18% (BURN: 6.81 +/- 0.36 ml/min/100 g, n = 8 vs SHAM: 5.77 +/- 0.29 ml/min/100 g, n = 8; P less than 0.025) and ERPF showed an insignificant 24% increase (BURN: 2.98 +/- 0.32 ml/min/100 g, n = 6 vs SHAM: 2.40 +/- 0.40 ml/min/100 g, n = 6; P less than 0.10), demonstrating a redistribution of flow. There was no local accumulation of lactate in blood, liver, or skeletal muscle and no derangement in P/L ratios. This study when compared to previous observations in sepsis suggests that (1) the flow redistribution of sepsis has features differentiating it from solely a "stress response".(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effective hepatic blood flow and hepatic bioenergy status in murine peritonitis.

To assess the effects of sepsis on effective hepatic blood flow (EHBF) and hepatic tissue bioenergy status 250-350 g rats underwent either sham laparotomy or cecal ligation and perforation (CLP). At 5-, 10-, and 20-hr intervals cardiac output (CO), EHBF, and tissue adenine nucleotide levels were measured. CLP rats showed a hyperdynamic response to sepsis at 20 hr, with CO increased by 25% over sham rats. At all time intervals studied EHBF was decreased and at 20 hr it was maximally decreased by 35%. Hepatic energy charge (HEC) was calculated from tissue adenine nucleotide measurements. HEC was not statistically different in sham and CLP rats at 5 hr and was 11 and 9% reduced from sham levels in CLP rats at 10 and 20 hr, respectively. Thus, EHBF is decreased very early in sepsis; before any changes in hepatic bioenergy status are noted. In this hyperdynamic model of sepsis EHBF is decreased early and decreases progressively with time which may contribute to the significant decrease in HEC that is demonstrated.

Adenine Nucleotides↗