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Biomedical subjects

G T Shires

Publications and source records attributed to G T Shires.

At least 55 records · Page 3Linked to original sources
PubMed1991

Risk for postoperative congestive heart failure.

To identify predictors of postoperative congestive heart failure (CHF), a high-risk population, mainly hypertensive and diabetic patients undergoing elective general operations, was studied. Of the 254 patients, 6 per cent had postoperative CHF. Among patients with preoperative cardiac disease (that is, previous myocardial infarction, valvular disease or CHF), 17 per cent had postoperative CHF; in contrast with less than 1 per cent of those without cardiac disease (p less than 0.001). Patients with diabetes were also at high risk (12 versus 2 per cent, p less than 0.005), particularly those with cardiac disease. Patients who had equal to or greater than 40 millimeters of mercury increases or decreases intraoperatively in mean arterial pressure in relation to preoperative baseline had increased postoperative failure rates (p less than 0.02). Of note, postoperative failure rates were highest among patients with less than 500 milliliters per hour of net intake (input and output) (p less than 0.03). Risk for postoperative CHF was restricted to patients with preoperative symptomatic cardiac disease and was especially high if patients also had diabetes. Intraoperative fluctuations in mean arterial pressure increased the probability of postoperative failure, while the intraoperative administration of higher net volumes of fluid was associated with decreased risk.

Aged↗
PubMed1991

Increased neutrophil mobilization and decreased chemotaxis during cortisol and epinephrine infusions.

Although hormones are putative mediators of neutrophil changes after injury, the effects of trauma-induced levels of plasma cortisol and epinephrine on circulating neutrophils have not been reported in humans. The dynamics of PMN mobilization and chemotaxis were evaluated during 19 infusions of epinephrine or cortisol or a combined infusion of both hormones in ten normal volunteers. Basal levels of epinephrine and cortisol increased during infusions to levels consistent with those reported following severe injury. Circulating neutrophil counts increased in parallel with plasma cortisol levels. Epinephrine mobilized the entire marginated pool of neutrophils, and the neutrophil half-life was extended from a normal of 6.6 hours to 10.4 hours by cortisol. Chemotaxis after six hours of epinephrine infusion was reduced compared with baseline chemotaxis. In four volunteers who had a second infusion of cortisol, chemotaxis was significantly depressed ten days after the infusion compared with baseline. From these data we conclude that stress levels of epinephrine mobilize the marginated pool of granulocytes into the circulating pool in a linear fashion, and cortisol raises the half-life of circulating neutrophils. Reduced neutrophil chemotaxis seen as a consequence of these infusions could account for some of the increased susceptibility to infection that occurs after major trauma.

Chemotaxis, Leukocyte↗
PubMed1990

Cytokine production in a model of wound healing: the appearance of MIP-1, MIP-2, cachectin/TNF and IL-1.

Macrophages are essential for normal wound repair and many of their effects on healing wounds are likely to be mediated by the secretion of cytokines. This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers. RNA for all four cytokines can be detected in wound inflammatory cells by polymerase chain reaction amplification throughout the first 7 days. Cachectin/TNF and IL 1 protein levels peaked on the first day after wound chamber implantation, and MIP-1 and MIP-2 were detected only on day 3. The data suggest that these cytokines participate in the early inflammatory response to wounding.

Animals↗
PubMed1990

Surgical rescue for failures of cirrhotic sclerotherapy.

Bleeding from gastroesophageal varices remains the most devastating complication of the portal hypertensive syndrome. Endoscopic sclerotherapy has emerged as the best initial treatment for bleeding varices because surgery is obviated and survival may be improved. However, sclerotherapy will fail and surgical rescue will be required in at least a third of patients. There are two viable surgical rescue procedures: shunt surgery and liver transplantation. This paper summarizes the available data and concludes that there is a role for both procedures.

Esophageal and Gastric Varices↗
PubMed1990

Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis.

Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier.

Animals↗
PubMed1990

Preoperative characteristics predicting intraoperative hypotension and hypertension among hypertensives and diabetics undergoing noncardiac surgery.

We prospectively studied patients with hypertension and diabetes undergoing elective noncardiac surgery with general anesthesia to test the hypothesis that patients at high risk for prognostically significant intraoperative hemodynamic instability could be identified by their preoperative characteristics. Specifically we hypothesized that patients with a low functional capacity, decreased plasma volume, or significant cardiac comorbidity would be at high risk for intraoperative hypotension and those with a history of severe hypertension would be at risk for intraoperative hypertension. Patients who had a preoperative mean arterial pressure (MAP) greater than or equal to 110, a walking distance of less than 400 m, or a plasma volume less than 3000 cc were at increased risk of intraoperative hypotension (i.e., more than 1 hour of greater than or equal to 20 mmHg decreases in the MAP). Hypotension was also more common among patients having intra-abdominal or vascular surgery, and among those who had operations longer than 2 hours. Patients older than 70 years or with a decreased plasma volume were at increased risk of having more than 15 minutes of intraoperative elevations of greater than or equal to 20 mmHg over the preoperative MAP in combination with intraoperative hypotension; this was also more common when surgery lasted more than 2 hours. Patients who had intraoperative hypotension tended to have an immediate decrease in MAP at the onset of anesthesia and were often purposefully maintained at MAPs less than their usual level during surgery with fentanyl and neuromuscular blocking agents. Patients who had intraoperative hyper/hypotension tended to have repeated elevations in MAP above their preoperative levels during the course of surgery, and such elevations precipitated interventions with neuromuscular blocking agents and/or fentanyl. Neither pattern was more common among patients who developed net intraoperative negative fluid balances. Both hypotension and hyper/hypotension were associated with increased renal and cardiac complications after operation. Patients with cardiac disease, especially diabetics, and those with negative fluid balances also had increased complications. Preoperative characteristics influence the susceptibility to intraoperative hypotension and hypertension, which are related to postoperative complications.

Aged↗
PubMed1990

Intraoperative blood pressure. What patterns identify patients at risk for postoperative complications?

While monitoring blood pressure is a routine part of intraoperative management, several methods have been proposed to characterize intraoperative hemodynamic patterns as predictors of postoperative complications. In this prospective study of a high-risk population of hypertensive and diabetic patients undergoing elective noncardiac surgery, one objective was to compare different approaches to the assessment of intraoperative hemodynamic patterns to identify those patterns most likely to be associated with postoperative complications. Twenty-one per cent of the 254 patients sustained cardiac or renal complications after operation. Patients with more than 1 hour of greater than or equal to 20-mmHg decreases in mean arterial pressure (MAP) or patients with less than 1 hour of greater than or equal to 20-mmHg decreases and more than 15 minutes of greater than or equal to 20-mmHg increases were at highest risk for postoperative complications. Together these two patterns had a 46% sensitivity rate and a 70% specificity rate in predicting postoperative complications. Using 20% change in intraoperative MAP produced results nearly identical to 20-mmHg changes. When the duration of 20-mmHg changes was accounted for, changes of a greater magnitude (e.g., 40 mmHg) were not significant independent predictors of complications. The use of the mean difference from preoperative MAP was misleading because patients who experienced both high and low MAPs tended to have nearly normal mean MAPs, but high complication rates. The absolute magnitude of intraoperative MAPs, regardless of the preoperative levels, also was evaluated. The overall mean intraoperative MAP was not a significant predictor of complications. Specific intraoperative MAPs (e.g., less than 70 mmHg and more than 120 mmHg) also were evaluated. While neither was a significant predictor, there was a trend for increased complications among patients whose MAPs decreased to less than 70 mmHg. Intraoperative blood pressure should be analyzed in relation to the patient's preoperative blood pressure. Prolonged changes of more than 20 mmHg or 20% in relation to preoperative levels were significantly related to complications.

Blood Pressure↗
PubMed1990

Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis.

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.

Ampicillin↗
PubMed1990

Pathophysiologic glucocorticoid elevations promote bacterial translocation after thermal injury.

Thermal injury results in transient elevations of plasma glucocorticoids and promotes translocation of bacteria from the gut to the mesenteric lymph nodes (MLN) in rats. Translocated organisms are quickly cleared following uncomplicated thermal injury. However, subsequent burn wound infection, in temporal association with sustained pathophysiologic elevations of plasma corticosterone, results in the continued presence of enteric bacteria in the MLN. To study the role of sustained pathophysiologic steroid elevations in the mediation of this prolonged bacterial translocation, Wistar rats were randomly placed in groups receiving one of the following: (i) a 30% total body surface area scald injury with placement of a subcutaneous corticosterone pellet, (ii) a 30% total body surface area scald and a sham pellet implantation, (iii) a sham burn and a corticosterone pellet implantation, or (iv) a sham burn and a sham pellet implantation. The animals were sacrificed on days 1 and 4 after injury, and cultures of the MLN, as well as the liver and spleen, were taken. Implantation of corticosterone pellets resulted in sustained elevations of plasma corticosterone compared with controls not receiving corticosterone pellets, similar to results seen in association with injury and infection. These pathophysiologic elevations were associated with the prolonged presence of organisms in the MLN (90% of burned rats with implanted corticosterone pellets versus 25% of rats with uncomplicated burns on postburn day 4; P less than 0.01), but only in the presence of burn injury. Pathophysiologic glucocorticoid elevations did not lead to progression of translocation to the viscera or blood. Thus, the pathophysiologic glucocorticoid response contributes to the translocation of enteric bacteria and their prolonged presence in the MLN after systemic injury.

Animals↗
PubMed1990

In vivo myocyte sodium activity and concentration during hemorrhagic shock.

The increase in intracellular Na+ concentration ([ Na+]i) and H2O content and decrease in K+ concentration during hemorrhagic shock have been observed. However, the state of the increased [Na+]i has never been defined. In this investigation double-barreled Na(+)-selective microelectrodes were used to directly measure in vivo intracellular Na+ activity (alpha Na) in skeletal muscle cells during prolonged hemorrhagic shock. Resting membrane potential, [Na+]i, and H2O content were also studied concomitantly. Sustained hemorrhagic shock with metabolic acidosis was produced in 12 rabbits after removal of approximately 40% of estimated blood volume under light anesthesia. During prolonged shock, resting membrane potentials of skeletal muscle cells depolarized to -74.7 +/- 1.7 mV from a base-line value of -92.6 +/- 0.4 mV. [Na+]i increased to 14.22 +/- 0.45 mmol/l from a base-line value of 11.50 +/- 0.32 mmol/l. Intracellular H2O content also had a 2.2% increase, whereas levels of [K+]i and extracellular H2O content decreased significantly. However, alpha i(Na) remained unchanged (4.07 +/- 0.19 mmol/l in base line and 4.04 +/- 0.20 mmol/l during shock). This makes the intracellular apparent activity coefficient for Na+ fall significantly from 0.356 in base line to 0.286 during shock. This result indicates that the extra Na+ that diffused into cell because of membrane dysfunction was bound to the fixed charges and/or compartmentalized into subcellular organelles. The unchanged alpha i(Na) also indicates that the depolarization of resting membrane potentials during sustained severe hypovolemia was not caused by the increased [Na+]i. The increase in extracellular [K+] during shock could account for the fall of the resting membrane potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans.

The in vivo alterations in organ-specific substrate processing and endogenous mediator production induced by endotoxin were investigated in healthy volunteers. An endotoxin bolus (20 U/kg) produced increased energy expenditure, hyperglycemia, hypoaminoacidemia, and an increase in circulating free fatty acids. These changes included increased peripheral lactate and free fatty acid output, along with increased peripheral uptake of glucose. Coordinately, there were increased splanchnic uptake of oxygen, lactate, amino acids, and free fatty acids, and increased splanchnic glucose output. There were no changes in circulating glucagon, or insulin and transient changes in epinephrine and cortisol were insufficient to explain the metabolic changes. Plasma cachectin levels peaked 90 min after the endotoxin infusion, and hepatic venous (HV) cachectin levels (peak 250 +/- 50 pg/ml) were consistently higher than arterial levels (peak 130 +/- 30 pg/ml, P less than 0.05 vs. HV). No interleukin 1 alpha or 1 beta was detected in the circulation. Circulating interleukin 6, measured by B.9 hybridoma proliferation, peaked 2 h after the endotoxin challenge (arterial, 16 +/- 2 U/ml; HV, 21 +/- 3 U/ml). The net cachectin efflux (approximately 7 micrograms) from the splanchnic organs demonstrates that these tissues are a major site for production of this cytokine. Hence, splanchnic tissues are likely influenced in a paracrine fashion by regional cachectin production and may also serve as a significant source for systemic appearance of this cytokine.

Adult↗
PubMed1990

The biologic characteristics of cytokines and their implication in surgical injury.

Cytokines are integral to normal homeostasis and to the response to injury. The biologic activities and synergistic actions of these proteins continue to be elucidated. In moderate quantities, these proteins likely confer such beneficial effects as myelostimulation, activation of immune cells and reprioritization of metabolic processes to provide substrates important in combating the results of injury. Exaggerated or prolonged production of these proteins, however, may produce detrimental effects that lead to a poor outcome. Specific antagonists against cytokines offer potential therapy in these instances of aberrant cytokine response.

Animals↗
PubMed1990

Elevated production of neutrophil leukotriene B4 precedes pulmonary failure in critically ill surgical patients.

Leukotriene B4, a potent neutrophil chemotactic factor, is also made by the neutrophil. Neutrophil function was studied in 12 patients at risk for the development of adult respiratory distress syndrome (ARDS) after admission to the surgical intensive care unit (ICU) to test the hypothesis that increased generation by the neutrophil generation of this mediator precedes the development of pulmonary failure. Peripheral blood neutrophils were tested for chemotaxis to f-met-leu-phe (fMLP) and leukotriene B4 (LTB4) and the generation of LTB4. Plasma was collected simultaneously for assay of C3a desArg levels. Five patients had ARDS a mean of 2.2 +/- 0.25 days after admission to the ICU. Neutrophil generation of LTB4 was significantly enhanced on ICU day 1 in these patients as compared with patients at risk for ARDS but not developing the syndrome (119.4 +/- 6.1 versus 101.0 +/- 5.1, per cent control, p less than 0.05). Chemotaxis to fMLP and LTB4 was significantly reduced in both groups of patients. However, neutrophil chemotaxis improved in patients who did not have pulmonary failure during the time in the ICU, whereas neutrophil chemotactic responsiveness worsened in patients who did have pulmonary failure. Plasma C3a desArg levels were significantly elevated over normal laboratory values on ICU day 1 in the ARDS patients (317.2 +/- 74.0 versus 132.0 +/- 16.0 milligrams per milliliter, p less than 0.01). These data indicate that LTB4 production by the neutrophil occurs concomitantly with complement activation, is a predictor of subsequent ARDS and may play a significant role in the development of pulmonary failure in critically ill surgical patients.

Chemotaxis, Leukocyte↗
PubMed1990

Serum cachectin/tumor necrosis factor in critically ill patients with burns correlates with infection and mortality.

Serum cachectin/tumor necrosis factor (TNF), a cytokine implicated in the pathogenesis of septic shock, may appear in the circulation during serious infection, but the frequency of detection of elevated serum levels during protracted critical burn injury is unknown. Serial serum samples taken from 43 critically ill patients with burns with and without sepsis were analyzed for TNF using an enzyme-linked immunosorbent assay (ELISA). TNF was detectable (greater than 34 picograms per milliliter) at one or more time points in 69 per cent of the patients with sepsis versus 33 per cent of those without sepsis, in 71 per cent of the patients who died versus only 31 per cent of the survivors and in only one healthy normal control patient (n = 21). The frequency of the appearance of TNF correlated with both infection and mortality rate. Moreover, all three patients with TNF levels greater than 540 picograms per milliliter died. Neither the size of the burn nor injury from inhalation correlated with detection of TNF. A subset of 16 patients was studied longitudinally from admission until resolution of injury and these data demonstrate that TNF appears transiently and repetitively in the circulation of patients during infection and protracted critical burn injury. Also, serum cortisol levels were significantly higher during sepsis and death in the absence of serum TNF, compared with sepsis and death with detectable cachectin, suggesting that cortisol may interact with the production or detection of this cytokine during ongoing infection and lethal injury. In this study, we have demonstrated that serum TNF is detectable with greater frequency and in higher concentration in patients with sepsis and in those who ultimately succumb to the burn injury, that serum TNF appears transiently and repetitively in the circulation during injury and that higher serum cortisol levels are correlated with the absence of serum TNF during sepsis and lethal injury.

Burns↗
PubMed1990

Additive effects of thermal injury and infection on the small bowel.

Thermal injury is associated with functional alterations of multiple organ systems, including the gastrointestinal tract. To study the effects of ongoing infection after thermal injury on bowel mass, composition, and blood flow, male Wistar rats were randomized to receive either 30% scald burn, 30% scald burn with Pseudomonas aeruginosa wound inoculation, sham burn, or sham burn with pair feeding to burned and infected animals. On days 3 and 7 after injury, intestinal blood flow was measured with 51Cr-labeled microspheres, and intestinal mass and composition were analyzed. Burned and infected animals demonstrated a chronic loss of small bowel mass not seen in burned animals without infection by day 7 after injury. Compositional alterations of the small bowels of burned and infected animals included protein wasting similar to but occurring earlier than that seen with anorexia alone and significantly decreased deoxyribonucleic acid and ribonucleic acid content, whereas tissue water content remained unchanged. These chronic intestinal alterations in the burned and infected group could not be explained by ongoing ischemia because intestinal blood flow in these animals was not significantly altered at either time point, implying mediation by other pathophysiologic mechanisms.

Animals↗
PubMed1989

Leukotriene B4 generation in patients with established pulmonary failure.

We investigated the cause of the reduced leukotriene B4 (LTB4) production seen in neutrophils from patients with established adult respiratory distress syndrome compared with control neutrophils. Lymphocytes/monocytes from controls were found to synergistically enhance the amount of LTB4 produced when incubated with neutrophils. This synergistic effect was not seen in cells from patients with adult respiratory distress syndrome. Fatty-acid analysis of neutrophils from patients with adult respiratory distress syndrome and controls showed remarkable similarity in all quantities of fatty acids measured except for arachidonic acid, where there was a 22% reduction in patients' cells compared with controls. Assay of the rate of generation of LTB4 and its degradation product, 20-hydroxy LTB4, revealed that reduced LTB4 generation in patients' neutrophils was not due to increased degradation of LTB4 by hydroxylase enzymes. When the amount of LTB4 being generated per milliliter of whole blood was analyzed in the patients with adult respiratory distress syndrome and compared with controls, it was determined that the potential to generate LTB4 in patients in the intensive care unit was three to five times greater than in controls.

Fatty Acids↗
PubMed1989

Assessment of the early cellular membrane response to live Escherichia coli bacteremia.

Alterations in skeletal muscle cellular function during septic shock have been previously demonstrated. However, whether these alterations represent a specific response to the septic state or are simply a consequence of low flow is uncertain. The present study was designed to evaluate the cellular membrane response to the early bacteremic state, prior to the onset of hemodynamic compromise. A clinically relevant model of sepsis was achieved in six mongrel dogs by intraarterial infusion of live Escherichia coli organisms and concurrent volume loading with lactated Ringer's solution. Four sham-treated dogs served as controls. Forty-eight hours after induction of sepsis, resting transmembrane potential (Em) was measured in a hindlimb adductor muscle. Contemporaneous muscle biopsy was performed for determination of transmembrane water and electrolyte distribution. The bacteremic state was associated with depolarization of Em to -79.7 +/- 1.2 mV from a basal value of -89.3 +/- 0.2 mV (P less than 0.01), while Em in the sham-treated group remained unchanged over the same time course. In addition, there was a significant increase in the calculated intracellular Na+ and Cl- concentrations in the septic group (P less than 0.02), while intracellular K+ was unchanged. These data are consistent with a selective increase in cell membrane permeability to Na+ and indicate that cellular alterations in skeletal muscle occur early in the septic course, in the absence of hemodynamic compromise. This alteration in membrane permeability appears to be common to cells of disparate organ systems in response to sepsis, and may represent a protean manifestation of cellular injury.

Adenosine Triphosphate↗