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Biomedical subjects

G T Shires

Publications and source records attributed to G T Shires.

At least 91 records · Page 5Linked to original sources
PubMed1988

Cytokine appearance in human endotoxemia and primate bacteremia.

The results of recent work have demonstrated that endotoxin elicits the production of several immunopeptide cytokines that likely mediate the development of septic shock. Bolus injection of endotoxin (20 units per kilogram of body weight) to four volunteers resulted in peak serum cachetin/tumor necrosis factor (TNF) levels of 358 +/- 166 picograms per milliliter within 90 minutes after challenge (p less than 0.05 versus base line) and peak serum interleukin-1 levels of 2.14 +/- 0.89 units per milliliter within two hours after challenge. By contrast, the infusion of a lethal dose of live Escherichia coli to four baboons revealed peak serum cachectin/TNF levels of 20,500 +/- 9,890 picograms per milliliter within 90 minutes after bacteria were given (p less than 0.05 versus base line) and peak interleukin-1 levels of 14.2 +/- 10.1 units per milliliter three hours after bacterial challenge. No detectable monokine levels were observed in either model six hours after challenge. Interferon-gamma levels reached a peak of 2.67 +/- 1.66 nanograms per milliliter in baboon sera at eight hours after bacterial infusion and was no longer detectable by 12 hours. Interferon-gamma was not detected in the sera of humans. These results suggest that the transient release of cachectin/TNF, followed by interleukin-1 and interferon-gamma, may participate in the cascade of events noted in overwhelming bacterial invasion.

Adult↗
PubMed1988

The effect of starvation and total parenteral nutrition on skeletal muscle amino acid content and membrane potential difference in normal man.

Skeletal muscle intracellular amino acids and transmembrane potential difference (Em) were measured in hospitalized volunteers during starvation and refeeding with total parenteral nutrition (TPN). Healthy volunteers underwent extremity amino acid flux measurement, percutaneous skeletal muscle biopsy and determination of skeletal muscle Em after ten days of starvation (ST), and after a subsequent ten day period of TPN. ST produced a significant (p less than 0.05) decrease in plasma essential amino acids when compared with normal ambulatory volunteers. Subsequent administration of TPN produced a significant extremity uptake of all essential amino acids except for threonine and uptake of the nonessential amino acids taurine, glutamate, tyrosine and arginine. ST produced a significant reduction in skeletal muscle free intracellular glutamine and a significant increase in isoleucine and leucine. These changes in free intracellular amino acids were not reversed by administration of TPN. At the conclusion of ten days of ST and ten days of TPN, there was a significant reduction (p less than 0.05) in skeletal muscle Em. The results demonstrate that abnormalities of intracellular amino acid concentrations and reduction of muscle Em are not specific to stress conditions, but rather they can be present during both unstressed ST and intravenous nutritional repletion.

Adult↗
PubMed1988

Surveillance for postoperative myocardial infarction after noncardiac operations.

Patients with postoperative myocardial infarction are frequently asymptomatic. Several follow-up strategies have been used to detect infarction or ischemia in asymptomatic patients. Different investigators have used quite different criteria to define patients at high risk. This study was done to evaluate these different approaches to selecting patients who should be monitored with electrocardiograms (ECG) or enzymes, or both, postoperatively, as well as different strategies for the timing of follow-up evaluation. A total of 232 patients, mostly hypertensive or diabetic, were evaluated before undergoing elective operations and were observed serially from the day of the operation until discharge or the sixth postoperative day with daily clinical evaluations, ECG and creatine kinase isoenzymes. Several follow-up strategies used in recent studies were evaluated for sensitivity and specificity in identifying the patient who had postoperative infarctions or ischemia. The most sensitive strategies would obtain ECG in asymptomatic patients on the day of the operation and the first two postoperative days. Several criteria for defining a high risk population were evaluated, including type of operation, age, history of cardiac disease, Goldman's cardiac risk classification and the results of the preoperative ECG. Monitoring of patients with an abnormal preoperative ECG would have identified 88 per cent of the patients with postoperative myocardial infarction and 63 per cent of the patients with definite ischemia. Goldman's risk class identified patients with a normal ECG who were at higher risk for postoperative ischemia.

Adult↗
PubMed1987

Increased susceptibility to infection due to infusion of exogenous chemotaxin.

Previous studies indicate that endogenous chemotaxins, such as the chemotactic factor C5a, may modulate the function of neutrophils (PMNs) and account for increased susceptibility to infection after injury. These effects were investigated by continuously infusing rats with saline or the chemotaxin formyl-methionyl-leucyl-phenylalanine (FMLP). Rats that sustained a full-thickness burn covering 30% of total body surface area and whose wounds were inoculated with Pseudomonas aeruginosa had a significantly shorter survival when FMLP was infused (6.5 +/- 0.91 days) than did saline-infused rats (9.9 +/- 0.83 days). Rats infused with FMLP had significantly more leukocytes in their burn wounds, significantly fewer PMNs in the circulating pool, and the same number of PMNs at the site of FMLP infusion compared with the saline-treated group. These findings support the hypothesis that chemotaxins generated by tissue injury or sepsis contribute to increased susceptibility to infection.

Animals↗
PubMed1987

Effect of hormonal and substrate backgrounds on cell membrane function in normal males.

Hormonal and substrate influences on in vivo cellular membrane function were evaluated in 15 healthy male volunteers. Each subject underwent serial evaluations of membrane function in the anterior tibialis muscle, as assessed by transcutaneous measurement of resting membrane potential (Em). Group A subjects (n = 9) underwent measurement of resting Em in the basal state and again during the 10th day of intravenous feeding (IVF). Group B subjects (n = 6) underwent measurement of resting Em in the basal state during epinephrine infusion and again during epinephrine infusion on the 7th day of IVF. Percutaneous needle biopsy of the vastus lateralis muscle permitted calculation of transmembrane electrolyte distribution from the Nernst equation, using the measured Em and the chloride space method. Hospitalization with intake of a defined-formula enteral diet for 3 days resulted in depolarization (P less than 0.05) of resting Em (-75.3 +/- 1.6 mV) compared with normal (-79.8 +/- 0.9 mV). Despite 10 days of subsequent IVF, further depolarization (P less than 0.05) of resting Em (-71.2 +/- 1.2 mV) was observed. In the dual presence of IVF and exogenous epinephrine infusion, there was an increase (P less than 0.05) in intracellular potassium concentration and repolarization of resting Em (-80.6 +/- 0.8 mV) to normal levels. These data indicate that hormonal background and substrate availability contribute to the in vivo modulation of cellular membrane function in human skeletal muscle, possibly through facilitation of sodium-dependent amino acid transport across the cell membrane.

Adult↗
PubMed1987

Intra-abdominal complications of cardiopulmonary bypass operations.

The records of 6,452 consecutive patients who underwent cardiopulmonary bypass procedures were examined for intra-abdominal complications. There were 60 complications in 51 patients for an incidence of 0.94 per cent. The mortality rate was 59 per cent. Complications included bleeding in the gastrointestinal tract in 20, intestinal ischemia in 16, acute cholecystitis in 11, pancreatitis in five, small intestinal obstruction in three, perforated ulcer in two, hepatic necrosis in two and splenic laceration in one instance. Clinical risk factors included advanced age, emergency operation, valvular surgical treatment, hypotension, intra-aortic balloon pump, pressors and reoperation. Patients with a prolonged pump time had an increased risk of intraabdominal complications (p less than 0.001).

Acute Disease↗
PubMed1987

Comparison of numerical and phenotypic leukocyte changes during constant hydrocortisone infusion in normal humans with those in thermally injured patients.

Twenty-four to 48 hours after thermal injury, percentages and number of T X mu or T4 lymphocytes decrease with little or no change in T X gamma or T8 cells. Additionally, the plasma hydrocortisone level is extremely elevated. Since administration of hydrocortisone to normal humans also produces a specific decrease in T X mu or T4 lymphocytes, it was hypothesized that burn induced elevations of hydrocortisone were responsible for the decrease in T X mu/T4 cells. In this study, normal humans were administered constant infusions of hydrocortisone for six hours, such that plasma levels were increased to an extent that mimics those 24 to 48 hours after thermal injury. Before, during and after infusion, percentages and numbers of lymphocytes, monocytes, granulocytes and T3, T4, T8, T11, HLA-DR and Leu7 lymphocytes were quantified by flow cytometry. Results were compared with those for patients with burns. The plasma hydrocortisone level rose to 49.0 micrograms per deciliter during infusion, similar to the mean of 47.5 micrograms per deciliter for patients with burns. Infused volunteers showed significant lymphopenia, monocytopenia and granulocytosis. Additionally, there were significant decreases in percentages of T3, T4 and T11 lymphocytes, no significant changes in percentages of T8 or HLA-DR and an increase in percentages of Leu7+ cells. These changes in lymphocyte subsets mimicked those of burn patients. Numbers of T3, T4 and T11 cells significantly decreased during hydrocortisone infusion while numbers of T8, HLA-DR and Leu7 lymphocytes did not change. Burn patients showed decreased numbers of T3 and T4 cells, but this T3/T4 lymphopenia was not as great as during hydrocortisone infusion. These results support the hypothesis that elevation of hydrocortisone is responsible for the lymphocyte phenotypic changes that occur in the early postburn period.

Adult↗
PubMed1987

Effect of hypothermia on cellular membrane function during low-flow extracorporeal circulation.

The use of systemic hypothermia is known to allow recovery from potentially lethal states of profound hypoperfusion or total circulatory arrest. While the cellular alterations accompanying states of decreased perfusion in skeletal muscle are well defined, little is known regarding the impact of coexistent hypothermia. To investigate this issue, nine dogs were placed on total cardiopulmonary bypass (CPB) and perfused in nonpulsatile fashion. The following flow and temperature parameters were used in three different perfusion models: 3.5 L/min/m2 at 23 degrees C (group A, n = 3), 1.6 L/min/m2 at 37 degrees C (group B, n = 3), and 1.6 L/min/m2 at 23 degrees C (group C, n = 3). Assessment of cellular function in a hind limb adductor muscle by measurement of resting transmembrane potential difference (Em) and determination of tissue electrolyte distribution in a biopsy specimen was performed in the control state and again after 60 minutes of total CPB. Low-flow/hypothermic CPB (group C) was associated with depolarization of resting Em to -63.3 +/- 3.2 mV from a control value of -87.0 +/- 1.3 mV (p less than 0.05), an increase in the calculated intracellular Na ([Na]i) to 16.4 +/- 4.0 mEq/L from a control value of 7.6 +/- 1.4 mEq/L (p less than 0.05), and an increase in the ratio of the selective membrane permeabilities of Na+ to K+ (pNa/pK), to 0.067 +/- 0.013 from a control value of 0.013 +/- 0.002 (p less than 0.05). In contrast, resting Em was maintained at -86.4 +/- 6.1 mv during normal-flow/hypothermic CPB (group A), while low-flow/normothermic CPB (group B) produced an intermediate depolarization to -75.2 +/- 3.0 mV (p less than 0.05). Neither [Na]i or pNa/pK was altered significantly in group A or group B dogs. These data characterize a physiologic alteration in the cellular membrane function of skeletal muscle during low-flow/hypothermic CPB, which is similar in many respects to that accompanying hemorrhagic shock. This suggests that during periods of profound hypothermia certain flow-related derangements in skeletal muscle are not obviated and may be exacerbated.

Animals↗
PubMed1987

Permeability of red-cell membrane to adenosine triphosphate (ATP) molecules during hemorrhagic shock.

The findings of decreased adenosine triphosphate (ATP) levels in liver, kidney, and other tissues of animals in hemorrhagic shock were the rationale for previous experimental attempts to improve cell function by administration of fluids that contained high concentrations of ATP. The beneficial effects of this resuscitation, which are still controversial, were attributed to cellular uptake of ATP--it was assumed that cell membranes are permeable to this substrate. The effect of a high concentration of ATP in extracellular medium on intracellular ATP content was studied by using red blood cells (RBCs) from rabbits in control (normal) and in hemorrhagic shock states. The glucose-depleted RBCs were incubated in medium with 5 mMol/L ATP, and their ATP concentration fell markedly to the same level as seen in glucose-depleted RBCs incubated without ATP. The decrease of ATP in glucose-repleted RBCs, incubated with or without ATP, also did not show any significant difference. Similar to parallel experiments that used normal RBCs, the high extracellular ATP content did not substantially affect the intracellular ATP concentration in RBCs from animals in shock. This study indicates that ATP molecules in extracellular medium cannot penetrate either the normal RBC membrane or the RBC membrane during shock.

Adenosine Triphosphate↗
PubMed1986

Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential.

Lethal infections are associated with cellular dysfunction as evidenced by a decrease in the resting transmembrane potential difference (Em) of skeletal muscle fibers. Endotoxin stimulation of macrophages evokes production of cachectin, a protein that has been implicated as a mediator of the lethal effects of endotoxemia. In the present study, rat skeletal muscle fiber Em decreased when incubated with recombinant human cachectin. The reduction of Em induced by cachectin occurred in a dose-related fashion and was inhibited by mAb against the monokine. Infusion of cachectin induced a decline of skeletal muscle Em in vivo, and suggests that cachectin may acutely mediate alterations of skeletal muscle membrane function after infection.

Animals↗
PubMed1986

Denervated splenopancreatic flap for chronic pancreatitis.

Various surgical procedures have addressed the disabling pain of chronic pancreatitis. Pain control must be weighed against the surgical morbidity and metabolic consequences of operation. Although ductal drainage works well for patients with dilated ducts, a new procedure was devised to avoid the diabetic morbidity of near-total pancreatectomy or pancreaticoduodenectomy in patients with small duct pancreatitis. Five patients have undergone the splenopancreatic flap procedure. The head of the pancreas is resected in a manner similar to near-total pancreatectomy, while the body and tail are denervated by dissection from their bed, with retrograde perfusion from the splenic hilus. All patients are alive a mean of 9 months after operation, and none is diabetic. Only one patient requires narcotic analgesics. Although none is asymptomatic, all have shown significant weight gain, and four of five are vocationally rehabilitated. Flap viability and the absence of transgastric varices have been documented by angiography and CT scanning. Although the durability of pain relief and islet cell function is unknown, these results suggest that this procedure may offer an alternative to major resection in chronic pancreatitis.

Adult↗
PubMed1986

Splenopancreatic disconnection. Improved selectivity of distal splenorenal shunt.

UNLABELLED: Distal splenorenal shunt (DSRS) improves survival from variceal bleeding in nonalcoholic cirrhotics but not in alcoholic subjects. The metabolic response after DSRS is also different in alcoholic and nonalcoholic cirrhotics. Portal perfusion, quality of blood perfusing the liver, cardiac output, and liver blood flow do not change in nonalcoholics. In alcoholics, portal perfusion is frequently lost (60%), quality of blood perfusing the liver decreases, and cardiac output and liver blood flow increase. It is proposed that portal flow is lost in alcoholics via pancreatic and colonic collaterals after surgery. Elimination of this sump by adding complete dissection of the splenic vein and division of the splenocolic ligament to DSRS (splenopancreatic disconnection, SPD) could preserve portal perfusion, decrease shunt loss of hepatotrophic factor, and improve survival in alcoholic cirrhotics. This report compares data 1 year after surgery in two groups of cirrhotics: group I (8 nonalcoholic; 16 alcoholic) had DSRS without SPD; group II (17 nonalcoholic; 11 alcoholic) received DSRS + SPD. METHODS: Portal perfusion grade, cardiac output (CO), liver blood flow (f), hepatic function (GEC), and hepatic volume (vol) were measured before and 1 year after surgery. Shunt loss of hepatotrophic factor was estimated by insulin response (change in plasma concentration over 10 minutes: AUC) after arginine stimulation. RESULTS: Groups I and II were similar before surgery. Metabolically, nonalcoholics remained stable after both DSRS and DSRS + SPD. After standard DSRS, alcoholics lost portal perfusion (75%, p less than 0.05), CO, and f increased (p less than 0.05), and quality of blood perfusing the liver was decreased (GEC/f: p less than 0.05). DSRS + SPD preserved portal perfusion better (p less than 0.05) in alcoholic cirrhotics than did DSRS alone. After DSRS + SPD, the metabolic response in alcoholics resembled that of nonalcoholics. CO, f, and GEC/f remained stable. These data show: DSRS + SPD preserves postoperative portal perfusion in alcoholic cirrhotics better than DSRS alone. Metabolic response to DSRS + SPD is similar in alcoholic and nonalcoholic cirrhotics. Because portal perfusion and metabolic integrity are preserved after DSRS + SPD, its use in alcoholic cirrhotics should improve survival.

Cardiac Output↗
PubMed1986

Improved burn center survival of patients with toxic epidermal necrolysis managed without corticosteroids.

Fifteen consecutive patients with toxic epidermal necrolysis or the Stevens-Johnson syndrome managed without corticosteroids after transfer to the burn center (group 2) are compared to a previous consecutive group of 15 who received high doses of these drugs (group 1). Group 2 had a 66% survival, which was a significant improvement compared to the 33% survival in group 1 (p = 0.057). In group 1, mortality was associated with loss of more than 50% of the body surface area skin. In group 2, mortality was related to advanced age and associated diseases. Age, extent of skin loss, progression of skin loss after burn center admission, incidence of abnormal liver function tests, and the incidence of septic complications were not significantly different in the two groups (p greater than 0.10). The incidence of detected esophageal slough was similar in both groups. Nonsteroid (group 2) management was associated with a decreased incidence of ulceration of gastrointestinal columnar epithelium, Candida sepsis, and an increased survival after septic complications. The combined experience of these 30 patients suggests that corticosteroids are contraindicated in the burn center management of toxic epidermal necrolysis and the Stevens-Johnson syndrome.

Adrenal Cortex Hormones↗
PubMed1986

Whole body oxygen utilization during acute carbon monoxide poisoning and isocapneic nitrogen hypoxia.

Carbon monoxide (CO) poisoning occurs frequently in victims of enclosed space fires, resulting in the formation of carboxyhemoglobin (COHb). Based on in vitro studies it has been suggested that CO poisoning causes a left shift of the oxyhemoglobin dissociation curve, decreasing peripheral oxygen extraction and exacerbating hypoxic injury. Formation of carboxycytochrome oxidase has also been postulated to act as a toxin by blocking cellular oxygen utilization. The effects of in vitro CO poisoning were evaluated in studies of 12 anesthetized, paralyzed dogs ventilated at 150 cc/kg/min. Six were subjected to CO poisoning by ventilation with a 0.5% CO in air inspirate. Six were ventilated with a mixture of air and nitrogen (N2) to produce a similar decrement of arterial oxyhemoglobin (aO2Hb) saturation. Arterial and mixed venous blood gases, thermal dilution cardiac output, and spectrophotometric arterial and mixed venous O2Hb and COHb saturation were measured. Oxygen consumption (VO2) and extraction (EXT) were calculated from these measurements and the CO and N2 groups were compared by ANOVA and Wilcoxon sign rank test as oxyhemoglobin was progressively decreased. There were no significant differences in VO2 or O2 EXT in these two sets of animals subjected to equivalent reductions of arterial oxyhemoglobin despite the fact that CO poisoning was the mode of desaturation in one group. These findings suggest that CO poisoning is primarily a hypoxic lesion caused by replacement of O2Hb by COHb. Effects predicted from in vitro studies may not be manifest in vivo due to physiologic responses active in the whole organism. This may have implications for the resuscitation of CO-injured patients.

Animals↗
PubMed1986

Grafting of cultured allogeneic epidermis on second- and third-degree burn wounds on 26 patients.

Twenty-six individuals with second- and third-degree burn wounds have been grafted with cultured allogeneic epidermal cells. These epidermal cell grafts were grown in culture from cadaver skin according to a technique which we have developed. After being grafted with cultured allogeneic epidermal cells, superficial wounds, e.g., donor sites, healed within 7 days, compared to 14 days for mirror image control sites. Deep second-degree burn wounds which were excised before grafting with cultured cells healed in a mean time of 10 days. Deep second-degree burn wounds which were not excised before grafting healed in a mean time of 14 days. The cultured cells produced rapid healing in 11 of the 12 patients with deep second-degree burn wounds. The deep second-degree wounds grafted with cultured allogeneic epidermal cells healed with results which were comparable to the deep second-degree wounds which were autografted. Grafts of cultured allogeneic epidermal cells placed on full-thickness, or third-degree burn, wounds did not grow well.

Adolescent↗
PubMed1986

The Budd-Chiari syndrome: a review.

Ascites, hepatomegaly, and abdominal pain constitute the classic triad of the Budd-Chiari syndrome of hepatic-vein or inferior-vena-cava obstruction. This condition was first mentioned by Budd in the mid 1800s and additional information was provided by Chiari in the 1890s. In nearly two-thirds of patients the exact etiology cannot be determined. The syndrome has, however, been associated with hypercoagulable states, neoplasms, trauma, medications, and congenital abnormalities. The diagnosis is difficult to make clinically; therefore, radiology plays a critical role in the workup of these patients. Nuclear medicine, sonography, CT, angiography, and MRI all provide valuable diagnostic information. These data combined with hepatic biopsy determine which patients should be treated by percutaneous angioplasty or surgery, and also determine the type of shunt to be performed (such as the mesoatrial shunt when the inferior vena cava is occluded or severely compressed). Noninvasive imaging is also useful in the follow-up of patients after both percutaneous angioplasty and surgery.

Angiography↗
PubMed1985

Extracellular fluid deficit following operation and its correction with Ringer's lactate. A reassessment.

The changes in extracellular fluid volume (ECV) in two groups of surgical patients, one receiving Ringer's lactate solution intraoperatively and the other receiving only dextrose and water, were assessed. A deficit in the ECV, as measured by radioactive sulfate, of 1.9 +/- 0.8 l (p less than 0.003) compared to the preoperative volume was found in the dextrose group. This was accompanied by a decrease in the mean creatinine clearance (-13% p less than 0.01), the mean urinary sodium excretion (-57% p less than 0.05), and the mean rate of clearance of the sulfate tracer (-18% p less than 0.01). The use of intraoperative Ringer's lactate (1660 cc +/- 96 cc) resulted in no change in the ECV, an increase in the mean creatinine clearance (+10% p less than 0.05), and no change in sodium excretion or tracer clearance. As a result of these findings, it appears that postoperative sodium retention is a physiologic response to a decreased ECV, which can be prevented by the administration of Ringer's lactate.

Adult↗