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Biomedical subjects

F B Cerra

Publications and source records attributed to F B Cerra.

At least 73 records · Page 4Linked to original sources
PubMed1991

Regulation of murine splenocyte responses by heparan sulfate.

Heparan sulfate is a biologically active glycosaminoglycan found in abundance in endothelium, epithelium, and connective tissues. Although heparan sulfate is an important part of the environment in which immune cells function, its effects on the immune system are largely unknown. When present during the first 24 h of an MLC consisting of MHC disparate murine splenocytes, heparan sulfate had a marked stimulatory effect on the proliferative response to alloantigens. Heparan sulfate also augmented the splenocyte response to suboptimal concentrations of the mitogens Con A, anti-CD3 mAb, and ionomycin. The stimulatory action of heparan sulfate was mediated, at least in part, by increased production of IL-1, because the increased splenocyte proliferation induced by heparan sulfate was substantially inhibited by anti-murine IL-1 alpha-antibodies. In contrast to these stimulatory effects, when heparan sulfate was added to MLC 48 to 72 h after onset, decreased splenocyte proliferation was observed. This inhibitory action was mediated by an increase in PGE2 production; the inhibitory effect could be abrogated with indomethacin. The fact that heparan sulfate is present on cells such as endothelial cells with which T cells interact and is released during activation of endothelial cells (thus making it available in soluble form to cells in the immune response) may allow heparan sulfate to play an important role in modulating cell-mediated immune responses in vivo.

Animals↗
PubMed1991

Nutrient modulation of inflammatory and immune function.

The metabolic response to injury occurs after a diverse group of surgical injuries including major surgical intervention, shock, infection, and sources of inflammation such as pancreatitis. The response is mediated by the macroendocrine system, the autonomic nervous system, and the cell-cell communication system. The clinical manifestations include now well-described clinical, physiologic, and metabolic characteristics. The approach of aggressive source control, invasive circulatory resuscitation, and nutrition/metabolic support has been associated with an overall reduction in morbidity and mortality. In those patients who do not respond to this approach, the disease process progresses to multiple organ failure syndrome with its associated high mortality. Altering the route of feeding, preventing single nutrient and generalized nutrient deficiency, and reducing nosocomial infections with selective gut decontamination have not significantly altered the course or outcome of the disease process in this latter group of patients with persistent hypermetabolism. The available data support the position that this persistent hypermetabolism represents abnormal metabolic regulation resulting in persistence of the inflammatory response with associated suppression of the immune defenses. A number of research approaches are being taken to understand and modulate this abnormal state of regulation. Because of the role of specific nutrients in these regulatory processes, beyond their role in classic nutrition support, nutrients such as arginine n-3 polyunsaturated fatty acids, and RNA are being evaluated for their ability to modulate inflammation and to improve immune function. Preliminary results are encouraging.

Arginine↗
PubMed1991

Increased dietary branched-chain amino acids do not improve growth in developing rats with chronic biliary obstruction.

We studied dietary branched-chain amino acid enrichment in cholestatic weanling rats. Growth was assessed with body weight, muscle weight and nitrogen balance. Systemic metabolic measurements that reflect liver function were evaluated, including plasma ammonia, albumin, amino acids, glucose, triglyceride and branched-chain ketoacids, as well as urinary carnitine excretion. Twenty-two rats underwent bile-duct ligation at 14 d of age. At weaning, 11 rats were fed a control diet and 11 an isoenergetic, isonitrogenous branched-chain amino acid-enriched diet for 3 wk, each with a sham-operated, pair-fed control. Body weights were similar in all four groups. Changes due to bile-duct ligation and not affected by the diet manipulation included lower plasma glucose, nitrogen balance and muscle weight, and higher triglyceride concentration, carnitine excretion and liver weight. Changes due to ligation that were normalized by dietary manipulation included plasma albumin, ammonia and total amino acid concentrations. The ratio of branched-chain to aromatic amino acids was decreased in ligated animals fed both diets; however, branched-chain amino acids were lower in the two groups fed more branched-chain amino acids.

Administration, Oral↗
PubMed1991

Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial.

The hypothesis that optimizing hemodynamics using pulmonary artery (PA) catheter (preoperative 'tune-up') would improve outcome in patients undergoing limb-salvage arterial surgery was tested. Eighty-nine patients were randomized to preoperative tune-up either in the surgical intensive care unit (SICU) (group 1) or the preinduction room (group 2) or to control (group 3). The tune-up consisted of fluid loading, afterload reduction, and/or inotropic support to achieve predetermined endpoints. Patients with a PA catheter had significantly fewer adverse intraoperative events (p less than 0.05), less postoperative cardiac morbidity (p less than 0.05), and less early graft thrombosis (p less than 0.05) than the control group. The overall study mortality rate was 3.4%, with a mortality rate of 9.5% in the control group and 1.5% in the PA catheter groups. There were no differences in ICU length of stay (LOS), hospital LOS, or total hospital costs, although the percentage of cost from complications was higher in group 3 (p greater than 0.05). In this group of patients, preoperative cardiac assessment and optimization is associated with improved outcome.

Aged↗
PubMed1991

Nitrogen oxide levels in patients after trauma and during sepsis.

The mediators responsible for maintenance of the hyperdynamic state and the low systemic vascular resistance (SVR) observed in sepsis have not been elucidated. Nitric oxide (.N = O) is a mediator with numerous functions, including regulation of vascular tone and a role in macrophage-mediated cytostasis and microbiostasis. Thirty-nine critically ill trauma and septic patients were studied to determine the relationship between .N = O production and the hyperdynamic state. high plasma levels of NO2-/NO3- (the stable end products of .N = O) were observed in septic patients (p less than 0.02). Low SVR and high endotoxin levels were associated with high NO2-/NO3- values (p = 0.029, p = 0.002). Changes in .N = O levels may mediate the vasodilation seen in sepsis. Low NO2-/NO3- levels were observed in trauma patients (p less than 0.001) and remained low even in the presence of sepsis (p = 0.001).

Adult↗
PubMed1991

Amino acid alterations and encephalopathy in the sepsis syndrome.

OBJECTIVE: To evaluate the role of amino acid profiles in septic encephalopathy. DESIGN: Retrospective analysis. SETTING: Medical wards and medical ICU of a university hospital. PATIENTS: Patients with infections and normal mental status were compared with patients with septic shock and altered sensorium. INTERVENTIONS: Plasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined. MEASUREMENTS AND MAIN RESULTS: Patients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 +/- 55 vs. 127 +/- 7 mmol/L) and the aromatic amino acids phenylalanine (122 +/- 19 vs. 74 +/- 3 mmol/L) and tryptophan (97 +/- 7 vs. 32 +/- 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 +/- 7 vs. 68 +/- 5 mmol/L) than patients with infections and normal sensorium (p less than .05). Aromatic amino acid levels correlated with APACHE II scores (R2 = .4, p less than .001) and mortality. APACHE II scores were higher in the septic shock patients (30 +/- 2 vs. 8 +/- 1, p less than .001), and these patients had a higher mortality rate (71% vs. 12%, p less than .01). Patients with septic shock who died had higher levels of ammonia (524 +/- 58 vs. 227 +/- 40 mmol/L, p less than .05) and sulfur-containing amino acids (172 +/- 31 vs. 61 +/- 7 mmol/L, p less than .05) than patients who survived. CONCLUSIONS: Plasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease.

Amino Acids↗
PubMed1991

Modular indirect calorimeter suitable for long-term measurements in multipatient intensive care units.

OBJECTIVE: The construction of an indirect calorimeter capable of long-term automated sequential monitoring of multiple patients in adult and pediatric ICUs. DESIGN: A prototype system utilizing modular engineering principles, including central respiratory mass spectrometer; validation by organic solvent combustion and nitrogen dilution methods, and Tissot spirometer. SETTING: Surgical and pediatric ICUs in a tertiary care university hospital. RESULTS: When expired minute volume was measured over a range of 4 to 28 L in six intubated patients, expired minute volume measured by the prototype system demonstrated a correlation coefficient of .998 compared with simultaneous expired minute volume measured by a Tissot spirometer. Organic solvent combustion demonstrated a maximum error of 3.8% for oxygen consumption (VO2) and an average error of 1.73 +/- 1.25% (SEM). The maximum error for the respiratory quotient was 3.0%, with an average error of 1.75 +/- 1.07%. VO2 (predicted) vs. VO2 (measured) demonstrated a correlation coefficient of .997. Validation with the nitrogen dilution method over a range of FIO2 from 0.21 to 0.60 demonstrated a maximum error of 7.9%, with an average error of -1.72 +/- 1.1% (n = 51). CONCLUSIONS: Indirect calorimetry by means of a shared system for measurements in multiple patients in ICUs is feasible and cost effective utilizing modular principles and a centralized respiratory gas analyzer.

Adult↗
PubMed1991

Dietary omega-3 fatty acids decrease mortality and Kupffer cell prostaglandin E2 production in a rat model of chronic sepsis.

We tested the hypothesis that substitution of omega-3 fat for dietary omega-6 fat would reduce mortality and decrease Kupffer cell prostaglandin E2 (PGE2) production in a rat model of chronic sepsis. Rats were fed via gastrostomy for 12 days with isonitrogenous, isocaloric diets containing 15% of calories as either safflower oil (omega-6) or a 10:1 mixture of menhaden oil (omega-3) and safflower oil. After five days of feeding, animals received an intra-abdominal abscess of defined bacterial content. Survivors were killed on post-laparotomy day 6 in conjunction with liver perfusion and protease liver digestion for Kupffer cell isolation. Kupffer cell PGE2 production was measured by radioimmunoassay after 18 hours of cell culture and again after stimulation with 0 LPS, 10 ng/ml LPS, and 10 micrograms/LPS. Mortality was decreased in menhaden oil-fed animals compared with safflower oil-fed animals (16% vs. 35%). Kupffer cell PGE2 production was decreased in menhaden oil-fed animals at 18 hours (354 +/- 54 vs. 570 +/- 95 pg/0.1 ml; p = 0.09) and after stimulation with 10 micrograms/ml LPS (140 +/- 41 vs. 288 +/- 45 pg/0.1 ml; p = 0.03) compared with safflower oil-fed animals.

Animals↗
PubMed1991

Increased urinary zinc excretion after thermal injury.

Urinary zinc excretion normally plays a minor role in zinc homeostasis; however, urinary zinc excretion is markedly elevated after trauma or surgery, and mechanism(s) for this zinc loss are poorly defined. In this study we evaluated multiple potential mechanisms for increased urinary zinc excretion in patients with thermal injury. We documented that patients with severe thermal injury had markedly elevated urinary zinc excretion. Above 20% total body surface area burn, however, the severity of thermal injury did not correlate with urinary zinc excretion. Serum zinc concentrations were depressed on initial evaluation and gradually increased during the hospital course, whereas peak urinary zinc excretion occurred 2 to 5 weeks after injury. Thus the depression in serum zinc concentration did not temporally relate to the observed pattern of hyperzincuria. Increased urinary zinc excretion also did not temporally relate to urinary excretion of the amino acids cysteine and histidine (both of which tightly bind zinc) nor to urinary 3-methylhistidine excretion, a marker of muscle breakdown. Urinary amylase excretion, a marker of renal tubular dysfunction, did follow the pattern of urinary zinc loss to some extent, although this correlation was not perfect. Increased oral intake of zinc via zinc supplements resulted in significantly increased urinary zinc excretion. Patients receiving total parenteral nutrition (TPN) did not have significantly increased urinary zinc excretion when compared with people receiving their total nutrient intake by mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Omega 3 polyunsaturated fatty acids as modulators of cellular function in the critically ill.

Continued improvement in outcome in ICU patients with the hypermetabolism-organ failure syndrome require a better understanding of the disease process. Current research is focusing on altered regulation at the cell membrane and nuclear levels. Cell culture models have provided insight into one possible mechanism, that of altered cell-cell communication with dysregulation of the associated parenchyma. Alteration of the PUFA content of the membrane of macrophages with omega 3 PUFA can be easily induced and maintained, and can alter cell membrane physical characteristics and how the membrane responds to LPS-stimulated prostanoid release. There is also an associated alteration in the release of monokine. These changes are associated with improvements in T lymphocyte response to antigen and in outcome from septic peritonitis. The precise mechanisms through which these effects occur are the subject of investigations, as are the clinical implications. Nonetheless, nutrient pharmacology with omega 3 PUFA may be a promising area of research that will have clinical applicability in ICU patients.

Cell Membrane↗
PubMed1990

The multiple organ failure syndrome.

Technology that has made it possible to resuscitate the severely sick and injured from formerly lethal shock has exposed a new disease. A potential sequela of ruptured aneurysm, acute pancreatitis, septic shock, burns, surgical complications, and trauma, MOF syndrome is the leading cause of death in surgical ICUs. Aggressive monitoring and prompt therapy can save lives.

Combined Modality Therapy↗
PubMed1990

APACHE II score does not predict multiple organ failure or mortality in postoperative surgical patients.

A clinical study was undertaken to evaluate the ability of the APACHE (acute physiology and chronic health care) II system to predict the development of multiple organ failure syndrome and subsequent mortality. The study was conducted in a university general surgery intensive care unit using the admission APACHE II score. Over a 1-year period, 92 patients qualified for the study, 24 of whom survived, 69 of whom suffered multiple organ failure syndrome, and 68 of whom died. The APACHE II score did not predict the development of multiple organ failure syndrome or mortality with clinical utility and significantly underestimated the potential for the development of multiple organ failure syndrome. Factors that did predict the development of multiple organ failure syndrome and mortality were the time-dependent changes in the PaO2-to-fraction of inspired oxygen ratio and serum lactate, creatinine, and bilirubin levels. Better markers of cell injury are needed for use in decision making and quality assurance analysis in surgical patients.

Humans↗
PubMed1990

Thermal injury effects on drug disposition: a prospective study with piperacillin.

The disposition of piperacillin was prospectively evaluated in nine severely burned patients who had normal renal and hepatic function. Wide interpatient variations were demonstrated in the drug's distribution volume, half-life, and clearance, with mean (+/- SD) values of 55.0 (+/- 44.2) liters, 3.6 (+/- 5.2) hours, and 14.9 (+/- 6.3) liters/hour, respectively. Piperacillin clearance was best explained by patient factors other than age, renal function, and the percentage of body surface area burns. Piperacillin disposition was related to the patients' serum albumin, total bilirubin, blood urea nitrogen, and the amount of urea nitrogen excreted daily in urine. Altered piperacillin disposition thus appeared to occur secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid therapy. The patient's physiologic and metabolic response to injury, along with age and renal function, should be considered when instituting treatment with piperacillin or other agents cleared from the body in a similar manner.

Adult↗
PubMed1990

Initial management of trauma. The first 5 minutes.

Trauma is the leading cause of death in young Americans and is responsible for the loss of more productive years of life than heart disease and cancer combined. Initial management of trauma consists of the establishment or maintenance of a patent airway, ensurance of adequate breathing, and resuscitation of the circulation. All of these are accomplished simultaneously with a cursory survey to identify immediately life-threatening injuries and to prevent permanent disability.

Critical Care↗
PubMed1990

Initial management of trauma. The next 60 minutes.

If and when hemodynamic stability has been achieved in a trauma patient, a detailed physical examination and appropriate diagnostic studies are performed. The successful management of trauma demands that immediately life-threatening problems receive top priority and that patients be continuously reexamined and problems reprioritized as conditions change. Finally, it is imperative that appropriate surgical evaluation and treatment be undertaken as soon as possible. Trauma patients should not be allowed to languish or undergo extensive examination in a hospital lacking surgical or other specialists trained to treat the problems identified. Transfer to another facility, whether for specialized diagnostic tests or for evaluation and treatment by surgical specialists, should be accomplished as quickly as possible.

Abdominal Injuries↗