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Biomedical subjects

F B Cerra

Publications and source records attributed to F B Cerra.

At least 91 records · Page 5Linked to original sources
PubMed1990

Growth hormone enables effective nutrition by peripheral vein in postoperative patients: a pilot study.

The purpose of this pilot study was to investigate the metabolic effects of growth hormone (GH) (Humatrope, Eli Lilly & Co., Indianapolis, IN) administration in postoperative (PO) patients receiving peripheral vein nutrition. Seven, well-nourished, nondiabetic patients undergoing elective surgical procedures were given either no drug (n = 3), GH 30 micrograms/kg/day (n = 2), or GH 60 micrograms/kg/day (n = 2) sub-Q daily until eating, up to 7 days PO. All the patients received 5% dextrose with electrolytes in the first 24 hours PO and then received calories at 80 +/- 5% of the measured resting energy expenditure (REE) and amino acid at 1 g/kg/day with electrolytes, vitamins, and minerals. There were no significant outcome differences between the 30 and 60 micrograms/kg/day groups and, therefore, these groups were analyzed together (n = 4). By day 6 of the study, the GH group had a significant reduction in the respiratory quotient (RQ) measured by indirect calorimetry; an increase in nitrogen retention; an increase in plasma transferrin concentrations; and an increase in plasma insulinlike growth factor (IGF1) concentration. There was no increase in blood glucose concentrations, or decrease in urinary 3-methylhistidine excretion; and no adverse effects occurred. We concluded that GH in PO patients on hypocaloric nutrition promoted protein synthesis, fat oxidation, and nitrogen retention. Effective parenteral nutritional support in postoperative adult patients can be achieved without the use of central vein access.

Adolescent↗
PubMed1990

Effects of treatment and the metabolic response to injury on drug clearance: a prospective study with piperacillin.

The disposition of piperacillin was prospectively evaluated in 11 critically ill surgical patients who had no evidence of pre-existing renal and hepatic disease. Interpatient variations were demonstrated in the drug's half-life, distribution volume, and clearance, with values of 1.50 +/- 2.05 (SD) h, 25.0 +/- 17.2 L, and 23.8 +/- 17.2 L/h, respectively. Variations in piperacillin disposition were best explained by serum concentrations of albumin, total protein, and bilirubin, and the amount of urea nitrogen excreted daily in urine. Age and renal function were moderately associated with piperacillin elimination rate and clearance. Altered piperacillin disposition thus appeared to occur as secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid/colloid therapy. These alterations may necessitate dosage modifications to achieve optimal patient response when treating patients with piperacillin as well as with other similar drugs eliminated via renal and nonrenal routes.

Adult↗
PubMed1990

Plasma amino acids in long-term models for obstructive versus toxic liver injury in developing rats.

We evaluated plasma amino acid (AA) concentrations associated with a histologically defined lesion caused by bile duct ligation (BDL) in developing rats. Nineteen rats that underwent BDL at 14 days of age had marked bile duct proliferation with bridging fibrosis, multifocal lobular necrosis, and minimal polymorphonuclear periportal infiltrate in their livers at sacrifice (11-31 days after ligation). These were compared to two age-matched control groups: 21 nonoperated rats and 22 sham-operated rats; and eight rats with cirrhosis caused by carbon tetrachloride. Signs of liver damage including jaundice, growth failure, bleeding, and ascites were accompanied by elevated bilirubin, ammonia, aspartate aminotransferase (AST), and alkaline phosphatase levels in BDL rats compared to controls. They had higher concentrations of total AAs, phenylalanine, tyrosine, and cyst(c)ine when compared to controls and to CCl4-treated rats. Micronodular cirrhosis was present in CCL4-treated rats with elevated AST and alkaline phosphatase levels. Glutamine and glutamate levels were higher in them than in BDL rats or controls, and branched chain AA levels were lower. These two chronic lesions, one obstructive and one hepatotoxic, both result in fibrotic change, but their metabolic abnormalities as reflected in plasma AA levels are distinct. We found that BDL is an appropriate model with which to study metabolic changes and growth failure due to chronic biliary stasis during its progression to frank cirrhosis.

Amino Acids↗
PubMed1990

Hepatic acute phase protein synthesis is indirectly regulated by tumor necrosis factor.

It has been proposed that tumor necrosis factor (TNF) is a direct regulator of postinjury hepatic protein synthesis. To test this hypothesis we investigated the total protein and specific acute phase protein synthesis response of murine hepatocytes to stimulation with mu-rTNF-alpha in vivo and in vitro. Total hepatocyte secretory protein synthesis was assessed by incorporation of [35-S] methionine into TCA-precipitated protein; and acute phase protein synthesis was assessed by induction of a 23-kD acute phase protein marker and by suppression of albumin synthesis determined by SDS-PAGE and autoradiography. We found that rTNF in vivo (8,000 units, IP injection) was associated with reduced total hepatocyte secretory protein synthesis (29 +/- 10%), increased synthesis of the 23-kD acute phase reactant (4.1 +/- 1.6-fold), and decreased albumin synthesis (0.68 +/- 0.2-fold) compared to saline-injected control animals. The in vitro stimulation of cultured murine hepatocytes directly with rTNF failed to demonstrate changes in total secretory protein synthesis or 23-kD protein; however, it did result in significant suppression of albumin synthesis (0.82 +/- 0.1-fold). In additional experiments, hepatocytes:nonparenchymal cell co-cultures stimulated with lipopolysaccharide (LPS) demonstrated protein synthesis changes similar to the in vivo TNF response including increased 23-kD protein and decreased albumin synthesis. These co-cultures demonstrated TNF production; however, addition of TNF antiserum during LPS stimulation had no effect on either 23-kD protein or albumin synthesis, despite the complete neutralization of TNF activity in the co-culture supernatants.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1990

Sepsis-induced diastolic dysfunction in chronic canine peritonitis.

A chronic canine model of hyperdynamic sepsis was achieved by cecal ligation and puncture (SEP) in conjunction with continuous high-volume fluid resuscitation. Cardiac function was evaluated using ultrasonic cardiac crystals placed across the major, minor, and wall thickness axes of the left ventricle, together with simultaneous arterial and ventricular pressure measurement. Seven to 10 days after crystal implantation, animals were randomized to either SEP (n = 10) or sham laparotomy control (n = 7). SEP dogs became febrile and lethargic, with elevated leukocyte counts and positive blood cultures for enteric organisms. They were also hyperdynamic, with significant increases in heart rate and cardiac output and a fall in systemic vascular resistance. Systolic blood pressure, stroke volume, and ejection fraction remained stable. Relative to control, the SEP group demonstrated a significant reduction in intrinsic contractility during systole, as measured by the heart rate and load-independent index of left ventricular performance Emax (P less than 0.01), confirming the observations of others. In addition, however, diastolic function also became markedly abnormal with a progressive increase in unstressed and end-diastolic ventricular volumes (P less than 0.05) and a significant decrease in myocardial compliance as quantitated by transmural pressure vs. volume-strain analysis. It is hypothesized that this increase in diastolic volume helps to maintain global cardiac performance during the hyperdynamic response to sepsis in the presence of adequate volume support.

Animals↗
PubMed1990

The syndrome of multiple organ failure.

Current technology has prolonged the life support of patients with organ failures. The onset of MOF follows an inciting event and develops a clinical pattern of lung, liver, and kidney failure. Laboratory evidence of the syndrome includes hyperbilirubinemia, hyperglycemia, increased blood lactate, and reduced levels of hepatic proteins. Energy expenditure in MOF is increased and severe sepsis or septic shock can initiate the process of hypermetabolism and MOF. Current therapy is aimed at source control, restoration of oxygen transport, and metabolic support. Critical care nursing provides a technological and humanistic approach in developing a supportive environment for patients and families. Scientific study of the effects of nursing interventions on patient outcomes is needed to evaluate critical care nursing activities.

Critical Care↗
PubMed1990

Other aspects of metabolic monitoring in critically ill patients.

Cardiopulmonary monitoring remains the mainstay of intensive-care unit utilization of clinical chemistry resources. Its focus has been on the restoration and maintenance of oxygen transport. Metabolic monitoring, a relatively new area of application for clinical chemistry technology, focuses on cell metabolism and on cell-cell interaction as a mechanism of metabolic regulation. This latter application of monitoring is developing as a result of a better understanding of the pathogenesis of organ dysfunction and disease processes in intensive-care unit patients. Some of the clinical chemistry technologies used include analyses for amino acids and polyunsaturated fatty acids, measurement of cytokine concentration and activity, nutritional assessment and monitoring, more sensitive monitors of liver function, and assessment of altered immunity in critically ill patients. Use of these technologies, along with specific support measures, offers new avenues for decreasing infectious complications and reducing mortality and morbidity of patients in intensive-care units.

Cell Communication↗
PubMed1990

The systemic septic response: concepts of pathogenesis.

Following resuscitation from shock, the clinical phase of persistent hypermetabolism is entered from which a substantial number of patients transcend into progressive organ failure and expire. The available epidemiologic, physiologic, and metabolic data are consistent with the position that a persistent degree of microcirculatory hypoxia, although it may be present in amounts that are below the sensitivity of current detection systems, becomes an increasingly less important etiologic factor as the organ failure disease progresses. Rather, aerobic metabolism appears to be the dominant mechanism of meeting the increased work loads and energy demands. There is an increasing body of evidence that cytokine release systemically, and increased cell-cell interaction through cytokines and prostanoids locally, may alter not only parenchymal function in the proximity of these mononuclear cells, but organ function at distant sites. If this latter hypothesis continues to be substantiated, it implies that the underlying cell and organ dysfunction may indeed be reversible if appropriate counter-regulatory mechanisms could be developed and the appropriate timing of their application understood.

Cytokines↗
PubMed1990

General principles of perioperative transplant care.

Along with the development of more specific and potent immunosuppressive agents, improvements in perioperative care of the allograft recipient have made transplantation of nonrenal organs a reality and contributed greatly to overall improvements in graft and patient survival. Thorough pretransplant evaluation, intensive care therapy and monitoring (when indicated), and meticulous postoperative care are essential to a successful outcome and to minimize the occurrence of complications.

Critical Care↗
PubMed1989

Modulation of Kupffer cell membrane phospholipid function by n-3 polyunsaturated fatty acids.

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to improve clinical outcome in a number of inflammatory diseases including burns and sepsis. One mechanism contributing to the anti-inflammatory effect is the incorporation of n-3 PUFAs into membrane phospholipids which decreases macrophage eicosanoid production. We hypothesize that an additional mechanism for their effects is an alteration of membrane signal transduction that decreases macrophage responsiveness to inflammatory stimuli. Kupffer cells, the fixed macrophages of the liver, were obtained from rats pair fed diets for 6 weeks with 15% of calories supplied as menhaden (high n-3), corn (control), or safflower (high n-6) oils. The effects of the dietary oils on Kupffer cell membrane signal transduction and eicosanoid production were assessed by measuring inositol phospholipid (PI) metabolism, intracellular calcium responses, and prostaglandin E2 (PGE2) production to the inflammatory signals endotoxin (LPS) and platelet activating factor (PAF). The menhaden oil diet resulted in significant incorporation of n-3 PUFAs into total cellular PUFAs compared to corn and safflower oil. (total n-3 PUFAs, 28.1% menhaden vs 2.1% corn vs 1.2% safflower, P less than 0.03). This incorporation altered signal transduction of PAF as both PI turnover (65% +/- 10% of corn oil) and calcium response (0.6-fold vs 5.0-fold for corn oil) were significantly reduced in the menhaden oil group. (P less than 0.05) The menhaden oil diet also reduced significantly PGE2 production in response to PAF and LPS (corn, 348 +/- 23 pg/ml; menhaden, 48 +/- 6 pg/ml, P less than 0.01). We conclude that, in addition to modulating eicosanoid production, n-3 PUFAs can also alter macrophage membrane signal transduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Enteral nutrition in hypermetabolic surgical patients.

Enteral nutrition is usually administered with premixed formulas and in a volume determined by the estimated total caloric need of the patient. The present study was undertaken to evaluate the nutritional outcome when isocaloric amounts of three commercial products were given as enteral nutrition in hypermetabolic surgical ICU patients. To qualify for the study, the patients had to be hypermetabolic and must have received and retained the volume of enteral formula estimated to meet energy and nutritional requirements for at least eight consecutive days. Caloric needs were defined as 30 to 35 total cal/kg.day. All data were prospectively collected; all patients had moderate to high-level metabolic stress after surgical intervention. Thirty-five patients participated in the study: 18 received a formula that was 23% amino acids, 20% fat, and had a nonprotein calorie/nitrogen (NPC/N) ratio of 97:1; ten patients received a formula with NPC/N 125:1 that was 17.5% protein and 35% fat; and seven patients received a formula with an NPC/N of 149:1 that was 15.3% amino acids and 2.5% fat. All formulas were given via nasoduodenal tube by continuous pump technique. Patients who received the low NPC/N had significantly greater N retention (p less than .05), increased plasma transferrin levels (p less than .05), and a lower RQ (p less than .05). There was a strong correlation between NPC/N and N retention and the increase in plasma transferrin levels. Thus, dosing enteral nutrition by total estimated caloric need does not presume optimal nutritional outcome. Formula composition is an important determinant of nutritional effect; formulas that have a lower NPC/N with more N and reduced calories as glucose demonstrate better nutritional results.

Adult↗
PubMed1989

Metabolic manifestations of multiple systems organ failure.

It is apparent that the metabolic response to injury as manifest in hypermetabolism and organ failure is a markedly different process from standard starvation. As such, it seems to have a different set of support principles that are probably better called metabolic support than nutritional support. The best treatment remains prevention by controlling the presence of dead tissue, injured tissue, and infection, and by appropriately restoring and maintaining oxygen transport. With control of the source and the restoration of oxygen transport, the primary mode of support becomes one of metabolic support. This modality is a support tool that appears to "buy time" and help control malnutrition as a comorbidity or comortality. The principles that have evolved in large part have been those of learning to do no harm. The prevention of substrate limited metabolism and effective support of visceral functions is now available until the late stage of the organ failure process. We still cannot control the catabolic stimulus and the autocannibalism of the skeletal muscle mass with the redistribution of nitrogen into the visceral protein mass and the use of amino acids as prime energy sources. The ability to control this stimulus will probably reside in our ability to understand and manipulate the mediator systems. We are now evolving effective support regimens for preserving organ structure and function and for promoting tissue repair. The route of administration as well as the time of administration of the regimen may have some impact on the disease course itself. When metabolic support has been applied in the setting of intelligent surgery and critical care, a progressive reduction in morbidity and mortality has been realized over the last several years such that the current mortality risk for the organ failure syndrome is in the 35 to 40 per cent range overall.

Bacterial Infections↗
PubMed1989

Role of monokines in altering hepatic metabolism in sepsis.

Multiple organ failure continues to be the primary cause of death after trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic response to injury to a syndrome of progressive organ failures and death. Risk factors include: perfusion deficits, persistent foci of dead or injured tissue, an uncontrolled focus of infection, the presence of the respiratory distress syndrome, persistent hypermetabolism, and preexisting fibrotic liver disease. Once initiated, most treatment modalities for the organ failure syndrome become progressively ineffective including: ventilation, antibiotics, nutrition, and surgery. The best treatment remains prevention and rapid control of risk factors including restoration of oxygen transport and aggressive nutrition support. There seems to be no treatment "magic bullet" either experimentally or clinically once the syndrome has occurred. The metabolic response to injury involves alterations in physiology and in the metabolism of carbohydrate, fat and amino acids. These changes seem to reflect the modulation of the end-organs by the mediator systems activated in response to the stress stimuli. The transition from hypermetabolism to organ failure appears to reflect the clinical appearance of liver failure. It is hypothesized that this liver failure may represent a state of regulatory dysfunction induced in large part by the activated hepatic macrophage, the Kupffer cell. The activation of these macrophages is hypothesized to represent the final stage of a series of stimulating events, eg. hypoxia, endotoxin, bacteria, and gut translocated toxins. The precise monokine(s) responsible are not yet completely characterized, although Interleukin-1 (IL-1) and tumor necrosis factor (TNF) appear to be involved as do prostaglandins (Pg) such as PgE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Hypermetabolism-organ failure syndrome: a metabolic response to injury.

The hypermetabolism-organ failure syndrome, a common disease entity, continues to account for most of the ICU deaths in surgical patients. This article reviews the phases of the response to injury process that culminates in organ failure and describes the patterns it may take. Current therapy for hypermetabolism-organ failure syndrome is also reviewed.

Energy Metabolism↗