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Biomedical subjects

F B Cerra

Publications and source records attributed to F B Cerra.

At least 109 records · Page 6Linked to original sources
PubMed1989

Hepatic dysfunction in multiple systems organ failure as a manifestation of altered cell-cell interaction.

Multiple organ failure continues to be the primary cause of death after trauma and sepsis. This clinical syndrome follows shock and resusitation and the transition from a hypermetabolic response 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, and preexisting fibrotic liver disease. The imitation of the syndrome represents the clinical manifestation of hepatic failure. It is hypothesized that this hepatic failure results from paracrine amplification with Kupffer cell induced hepatocyte cytotoxicity. 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.

Animals↗
PubMed1988

Direct effects of endotoxin on hepatocytes. Synthesis of a specific secretory protein.

The synthesis of acute-phase proteins by the liver during sepsis has been thought to be induced primarily by monokines released from activated macrophages, although glucocorticoid hormones may also stimulate this process to a lesser degree. According to this concept, synthesis of these proteins following administration of bacterial endotoxins would be an indirect effect and would not reflect a direct interaction of the endotoxin molecule with the hepatic parenchymal cell. We observed, however, that the synthesis of a 23-kilodalton protein was stimulated directly by the addition of lipopolysaccharide to cultures of primary mouse hepatocytes. The synthesis of this protein was also stimulated by glucocorticoids and interleukin 1. These findings demonstrate that certain hepatic proteins are subject to complex regulation by several factors thought to be important mediators of sepsis; in addition, they suggest that hepatic parenchymal cells may have the intrinsic capacity to respond directly to bacterial endotoxins.

Animals↗
PubMed1988

Endotoxin modulation of hepatocyte secretory and cellular protein synthesis is mediated by Kupffer cells.

We hypothesize that alterations of hepatocyte function in sepsis are modulated by endotoxin (lipopolysaccharide)-triggered Kupffer cells. In the present experiments the effect of lipopolysaccharide on secreted and cellular proteins synthesized by hepatocytes cultured alone or cocultured with Kupffer cells was investigated using polyacrylamide gel electrophoresis. Lipopolysaccharide had no direct effect on the types or amounts of secreted proteins synthesized by hepatocytes alone. Kupffer cells coculturing resulted in increased synthesis of some hepatocyte proteins (68k and 23k) whose production was not altered by lipopolysaccharide. In contrast, addition of lipopolysaccharide to the hepatocyte-Kupffer cell coculture substantially decreased synthesis of several proteins (73k, 66k, and 35k). Despite an overall decrease in protein synthesis of hepatocytes cocultured with Kupffer cells after the addition of lipopolysaccharide, there was increased synthesis of several individual proteins (58k and 44k). Similar effects were seen in synthesis of cellular protein. The addition of recombinant interleukin 1 to hepatocytes alone or in coculture had no effect on the amount or type of protein synthesized. We conclude that Kupffer cells regulate the types and amounts of individual proteins synthesized by hepatocytes via mediators other than interleukin 1.

Animals↗
PubMed1988

Fatty acid intake and Kupffer cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation.

Diets high in n-3 fatty acids appear to have an anti-inflammatory effect, which is thought to be due to decreased macrophage prostaglandin (PG) and thromboxane (Tx) production after incorporation of these fatty acids into cell membrane phospholipids. The effect of n-3 fatty acids incorporation on macrophage monokine release in response to septic stimuli is not well established. Kupffer cells, the fixed macrophages of the liver, were obtained from rats fed diets with fat sources derived from corn oil (CO, control), fish oil (FO, high in n-3 fatty acids), or safflower oil (SO, high in n-6 fatty acids) for 2 or 6 weeks. After exposure to bacterial lipopolysaccharide, Kupffer cells from rats fed FO for 2 or 6 weeks produced less PG and Tx than Kupffer cells from rats fed CO or SO. After 2 weeks of defined diets, interleukin-1 (IL-1) and tumor necrosis factor release were not affected by dietary fat source. In contrast, after 6 weeks of feeding, Kupffer cells from both the FO and the SO groups released less IL-1 and tumor necrosis factor when triggered by lipopolysaccharide than Kupffer's cells from animals fed the control diet that contained CO. These data suggest that altered monokine release from macrophages may contribute to the anti-inflammatory effect of diets high in n-3 fatty acids. Also shown in our results is that prolonged changes in membrane phospholipid content induced by dietary fat source can influence not only PG and Tx production but monokine release as well.

Animals↗
PubMed1988

Enteral nutrition does not prevent multiple organ failure syndrome (MOFS) after sepsis.

Gut malnutrition in patients with persistent hypermetabolism is hypothesized to be an important factor in postseptic multiple organ failure syndrome (MOFS). The hypothesis was made that enteral nutrition (EN) started at the onset of hypermetabolism could reduce the incidence of MOFS. Sixty-six patients with persistent hypermetabolism 4 to 6 days after onset of sepsis were prospectively randomized to receive either parenteral nutrition (PN) or enteral nutrition (EN) at 1.5 gm protein/kg/day and 30 nonprotein calories/kg/day; the EN and TPN were of the same composition. There was no reduction in either the incidence of MOFS or mortality attributable to the route of nutrition administration. The PN group tended to have better visceral protein support; the EN group had more gut complications. When analyzed, the type of formula given did have an effect on the nutritional outcome but not on the mortality rate. A formula with a nonprotein-calorie-to-nitrogen ratio of 100:1 was associated with more nitrogen retention, higher levels of visceral proteins, and better gut tolerance. The route of nutrition administration does not seem to affect the incidence of postseptic MOFS or mortality when hypermetabolism is already present and when commercially available nutritional formulas are used. The relationships among the route of nutrition, the type of enteral formula, and the disease process of hypermetabolism and MOFS appear to be complex and require much more investigation before the role of the gut and enteral nutrition can be defined.

Energy Intake↗
PubMed1988

Pyrochemiluminescence: real-time, cost-effective method for determining total urinary nitrogen in clinical nitrogen-balance studies.

Total urinary nitrogen (TUN) determinations for nitrogen-balance studies were traditionally performed by the Kjeldahl method, but this method is laborious, hazardous, prone to error, and no longer widely available in most clinical laboratories. During the last several decades, urinary urea nitrogen (UUN) determinations have replaced TUN as an index of urinary nitrogen excretion in many clinical laboratories, owing to its ease of determination, decreased cost, and wide availability. However, the validity of using UUN for estimating nitrogen loss has been questioned in many disease states, owing to wide variations in the proportional amount of urea found in TUN. Chemiluminescence has been proposed as an alternative to the Kjeldahl method for TUN. TUN values obtained from 24-h urine collections measured by both micro-Kjeldahl (x) and Pyrochemiluminescence (y) (Antek Instruments, Inc.) techniques were comparable by linear regression analysis: n = 97; r = 0.996; r2 = 0.992; y = 1.048x - 0.606; P less than 0.001. Automated induction of samples and calculation of results allows up to 42 samples to be run unattended. This dramatically reduces labor and overall costs for TUN determinations, while providing a more accurate and economical assessment of nitrogen excretion than UUN in a clinical setting.

Cost-Benefit Analysis↗
PubMed1988

Nutritional monitoring in the ICU: rational and practical application.

The metabolic response to injury can induce a state of hypermetabolism that results in the rapid loss of the body nitrogen, so that a critical reduction in lean body mass that affects morbidity and mortality can occur in a short period of time. The process also induces a redistribution of the body nitrogen away from the skeletal mass and toward the viscera and areas of increased metabolic activity, such as the surgical wound, the zone of inflammation, and toward cells producing mediators. Exogenously administered nitrogen is not very effective in reducing the rate of catabolism. It can, however, increase the rate of protein synthesis. In so doing, the rate of net catabolism is reduced. The modified amino acids appear to be much more effective in achieving these ends than do the standard amino acid formulas. Visceral protein synthesis is difficult to use as an index of visceral protein malnutrition in the settings where the metabolic response to injury is also present. These proteins and the acute-phase reactants may not have the sensitivity and specificity to discriminate between visceral protein malnutrition and the changes induced by the metabolic response to injury. The practical clinical endpoint, then, in managing the nitrogen economy during the metabolic response to injury is to provide adequate nitrogen intake, achieving 2 to 4 gm of positive nitrogen balance whenever possible. Caloric (energy) equilibrium can be achieved. Calories in excess of demand or glucose in excess of the ability to effectively oxidize, however, can have detrimental effects in some settings. Expired gas analysis can be useful in this context. Achieving caloric equilibrium does not appear to be essential. The reduction in malnutrition as a cofactor in morbidity and mortality appears to come from achieving nitrogen equilibrium. These alterations in metabolism induced by metabolic stress and the changes in nutrient requirements have been called metabolic support and are summarized in Table 3. The end-points of metabolic support, whenever possible, become 2 to 4 gm of positive nitrogen balance with an amino acid load that will achieve that balance; support of visceral protein synthesis as judged by acute-phase reactant and hepatic protein (e.g., transferrin) synthesis; and avoiding complications of excess VCO2 and urea production (BUN less than 110 mg per cent) (Fig. 5).

Carbohydrate Metabolism↗
PubMed1988

Hypermetabolism/organ failure: the role of the activated macrophage as a metabolic regulator.

Multiple organ failure continues as the main cause of death after burns, trauma and sepsis. This clinical syndrome represents the transition from a hypermetabolic response to injury to a setting of clinical 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 in the organ failure syndrome, most treatment modalities become progressively ineffective, including: ventilation, antibiotics, nutrition, and surgery. The best treatment remains prevention with rapid control of the source and restoration of oxygen transport. The 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 stimulus. The transition from hypermetabolism to organ failure appears to reflect the clinical appearance of liver failure. It is currently hypothesized that this liver failure represents a state of regulatory dysfunction induced by the activated hepatic macrophage, the Kupffer cell. This same process may also influence metabolic failure in other organs where this cell-cell regulation can occur, e.g. kidney, lung. The activation of these macrophages is hypothesized to represent the final stage of a series of continuous stimulating events, eg. hypoxia, endotoxin, bacteria, and gut translocated toxins. The precise monokine(s) responsible are not yet completely characterized. Treatment consists of the modalities outlined above and the employment of aggressive metabolic (nutritional) support.

Humans↗
PubMed1988

Intrapatient variation of aminoglycoside pharmacokinetics in critically ill surgery patients.

Intrapatient variation in aminoglycoside pharmacokinetics was studied in 100 critically ill surgery patients, and the relationships between aminoglycoside pharmacokinetics and physiological variables were evaluated. A one-compartment model and the DataMed Clinical Support Service System were used to calculate pharmacokinetic values from serum concentration-time data and to provide individualized dosage regimens. A total of 323 pharmacokinetic analyses (2 to 9 per patient) were performed. There were significant intrapatient differences in clearance (CL) between analyses, and there was a downward trend in elimination rate constant (k) and an upward trend in half-life (t1/2) with time. There were no significant differences in mean volume of distribution (V) between analyses and no strong correlations of V, k, and CL between analyses. The total daily dosage necessary to provide the desired serum aminoglycoside concentration decreased with time, while the dosing interval increased. The mean absolute changes in t1/2, V, and CL between analyses were 3.2 hr, 7.1 L, and 15.7 mL/min, respectively. Dosing regimen changes were required in 90% of the patients, regardless of the time between analyses, including 75% (24/32) of the patients with analyses on consecutive days. There were weak correlations between changes in serum creatinine concentration and changes in dosing interval and between changes in weight and changes in V. Changes in calculated creatinine clearance, BUN, pulmonary capillary wedge pressure, central venous pressure, systemic vascular resistance, cardiac index, input minus output, and maximum temperature did not result in strong correlations with k, t1/2, V, and CL by univariate or multivariate regression analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effect of infusion pump fill-stroke flow interruption on response to sodium nitroprusside in surgical patients.

The influence of the piston-cassette pump fill stroke on the pharmacodynamic response to sodium nitroprusside was evaluated prospectively in 10 adult patients in the surgical intensive-care unit. Simultaneous analog recordings of blood pressure and fill stroke were made over three complete pump fill cycles in each patient. Sodium nitroprusside flow rates and concentrations were recorded throughout the data-collection period. Analysis was based on the maximum pressure obtained during the two-minute baseline period before a fill stroke (Pmax baseline), the pressure at the initiation of the fill stroke (P initial), and the maximum pressure obtained during the two-minute period after the fill stroke (Pmax postfill). The maximum systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) during the baseline and post-fill-stroke periods were significantly different. The mean (+/- S.D.) variability in pressure between the time periods Pmax baseline and Pmax postfill was 3.9 +/- 5.8 mm Hg for SBP (range, -8 to +16), 3.5 +/- 5.7 mm Hg for DBP (range, -7 to +13), and 3.6 +/- 5.6 mm Hg for MBP (range, -7 to +14). The likelihood of a pharmacodynamic change was inconsistent both between and within patients. Within patients the difference between cycles for the variability between time periods ranged from a minimum of 2 mm Hg to a maximum of 16 mm Hg for SBP, 2 mm Hg to 17 mm Hg for DBP, and 1 mm Hg to 17 mm Hg for MBP. The variability within the baseline period (Pmax baseline - P initial) in SBP was significantly greater than the variability between the time periods, while the differences for DBP and MBP were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Physiology and metabolism in isolated viral septicemia. Further evidence of an organism-independent, host-dependent response.

The hypothesis has been advanced that the human systemic septic response is a function of the host and not of the type of infecting organism. Metabolic and physiologic data from five immunosuppressed transplant recipients with isolated cytomegaloviral sepsis and viremia were prospectively evaluated. Serial cultures obtained from lung, sputum, urine, wound, blood, and invasive lines were positive for virus and negative for bacterial or fungal pathogens. The results were compared with two data banks derived from either victims of multiple trauma without sepsis or surgical patients with early bacterial or fungal sepsis. Statistically significant differences between the patients and the nonseptic reference group were noted for cardiac index, total peripheral resistance, arteriovenous oxygen content difference, oxygen consumption, and levels of triglycerides, proline, phenylalanine, tyrosine, alpha-aminobutyrate, and alanine. No such differences were present for these data compared with the septic reference group. Physiologic data obtained just before death in three patients indicated a failure of oxygen transport. It appears that the systemic septic response to viral agents is indistinguishable by physiologic and metabolic criteria from that resulting from bacterial or fungal agents.

Adult↗
PubMed1987

Renal failure and mortality after nephrectomy for severe trauma in multiply-injured patient: no inordinate risk.

It was recently reported that renal loss by partial or total nephrectomy for renal trauma increases the rates of acute renal failure and death in the multiply-injured patient. Because our preference has been for immediate surgical intervention in such patients, a retrospective review was performed to ascertain the effect of partial or total nephrectomy. Eighty-eight patients met the criteria of multiple injuries including severe renal injuries (laceration, rupture, or pedicle injury) and availability of renal function data. Partial or total nephrectomy had been performed in 50 patients, renorrhaphy in 23, and 15 were managed without renal operation. In patients with renal lacerations, the numbers of associated injuries (including intra-abdominal injuries) were similar to those managed conservatively or by operation, and the rates of acute renal failure and mortality were the same with conservative management, renorrhaphy, or nephrectomy. Patients with renal pedicle injuries who had a nephrectomy did have a higher rate of acute renal failure than those managed conservatively (75% vs 0%; p less than 0.05), but they also had more associated injuries (2.8 vs. 1.6/patient; p less than 0.04) and they were older. These two factors, rather than the nephrectomy, probably accounted for the greater rates of acute renal failure and death.

Acute Kidney Injury↗