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F B Cerra

Publications and source records attributed to F B Cerra.

At least 145 records · Page 8Linked to original sources
PubMed1985

Modulation of hepatocyte protein synthesis during co-cultivation with macrophage-rich peritoneal cells in vitro.

The etiology of hepatic failure associated with the multiple-system organ failure syndrome is poorly understood. Because of indirect evidence suggesting that macrophages or Kupffer's cells may play a role in this phenomenon, macrophage-rich peritoneal cells were co-cultured with isolated rat hepatocytes. Following co-culture, the rate of hepatocyte protein synthesis, quantitated by counts per minute of tritiated leucine incorporated into protein, was significantly diminished. This modulation of hepatocyte function was not enhanced by prestimulation of macrophage-rich peritoneal cells in vivo by casein, thioglycolate, or Corynebacterium parvum. Addition of the macrophage secretory product lysozyme did not alter hepatocyte protein synthesis. This cell-mediated effect on hepatocytes could not be recreated by a macrophage-rich peritoneal cells supernatant transfer. These results support the idea that cells of macrophage lineage could mediate changes in hepatocyte function that may, in turn, play a role in the etiology of hepatic malfunction associated with the multiple-system organ failure syndrome.

Animals↗
PubMed1985

Prolonged surgical intensive care. A useful allocation of medical resources.

To determine factors related to outcome following prolonged stays in the surgical intensive care unit (ICU), we reviewed the charts of all 59 patients who required surgical ICU stays of one week or longer during 1982 (63 admissions). Overall ICU survival was 58.7% and varied inversely with acute illness severity, length of ICU stay, and hospital cost. The need for renal dialysis and prolonged mechanical ventilatory support were associated with bad outcomes. Age did not affect ICU survival. Follow-up survival was 33% of the original group or 56.8% of ICU survivors. Poor chronic health was associated with a high late mortality. The functional status of surviving patients was satisfactory, with 18 of 21 patients living independently. We conclude that there is significant survival following prolonged ICU therapy, and that, although identifiable factors related to outcome exist, none alone permit the discontinuation of therapy on an individual basis.

Adult↗
PubMed1985

Metabolic effects of pretreatment with Escherichia coli J5 antiserum on guinea pig gram-negative bacterial sepsis.

Antiserum raised to a rough mutant Escherichia coli, termed J5 (anti-J5 RS), protected against lethal gram-negative bacterial sepsis in a guinea pig model when animals were pretreated with both antiserum and heparin. This same model was used to examine and compare the effects of pretreatment with anti-J5 RS, normal rabbit serum (NRS), or saline, each +/- heparin on physiologic and metabolic parameters during a septic insult. Results demonstrated that leukopenia and thrombocytopenia occurred to a similar degree in all pretreatment groups; no significant leuko- or thrombostasis was noted on examination of histologic specimens; complement activation was maximal in those animals receiving anti-J5 RS alone without heparin; the most abnormal amino acid profile was present in the NRS + heparin group; and only the anti-J5 RS + heparin group did not develop glomerular lesions indicative of disseminated intravascular coagulation. A complement-mediated cell aggregation-type injury does not appear to occur in this model. It is hypothesized that both excessive complement and coagulation system activation occur after bacterial challenge when antibody directed against the bacteria is present (anti-J5 RS) leading to antigen-antibody complex formation and complement and coagulation cascade activation. Heparin may block either or both these cascade systems allowing enhanced, antibody-mediated opsonization and clearance of blood-borne bacteria, thus preventing end-organ alterations and organ failure during sepsis when combined with anti-J5 RS.

Amino Acids↗
PubMed1985

Macrophage-mediated modulation of hepatic function in multiple-system failure.

Hepatic insufficiency associated with the multiple-system organ-failure (MSOF) syndrome is a frequent sequellae of sepsis and severe trauma. Although its etiology is poorly understood, there is a growing literature suggesting that it may be mediated in part by secretory products of cells of monocyte/macrophage lineage including Kupffer cells. Several investigators have reported in vitro macrophage/Kupffer cell-mediated cytotoxicity toward target cells following appropriate stimulation. In addition, in vivo hepatocyte toxicity has been documented following activation of the reticuloendothelial system. The role of several secretory products including active oxygen intermediates, neutral proteases, and interleukin 1 in this cell-mediated model of hepatocellular modulation is reviewed.

Cell Communication↗
PubMed1985

Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells. II. Mediation by soluble transferrable factors.

We have previously reported a diminution of protein synthesis by isolated Sprague-Dawley rat hepatocytes following coculture with lipopolysaccharide-triggered nonparenchymal liver cells (NPC) containing 30-40% Kupffer cells. It is possible that this cell-mediated modulation of hepatocyte function represents an in vitro model for hepatic insufficiency occurring in patients with the multiple system organ failure syndrome. In the present report we have determined that supernatant from lipopolysaccharide-triggered NPC was itself capable of inhibiting hepatocyte protein synthesis in a similar fashion. This effect was directly related to the concentration of the supernatant and to the period of exposure to the supernatant. The ability to inhibit hepatocyte protein synthesis by a NPC supernatant suggests that this cell-mediated event is caused at least in part by a relatively stable soluble factor(s) secreted by LPS triggered NPC. Although reagent H2O2 will inhibit protein synthesis when added to hepatocyte culture, LPS-stimulated NPC do not release H2O2 and do not show chemiluminescence--an in vitro correlate of the respiratory burst. Nonspecific protease inhibitors added to the coculture similarly do not influence the system. Combined with other evidence, the soluble mediators do not seem to be the result of oxidative or proteolytic secretions of the effector cells.

Animals↗
PubMed1985

Modulation of hepatocyte protein synthesis by endotoxin-activated Kupffer cells. III. Evidence for the role of a monokine similar to but not identical with interleukin-1.

The authors previously reported that unstimulated peritoneal macrophages and LPS stimulated Kupffer cell-rich nonparenchymal liver cells (NPC) can inhibit protein synthesis in cultured rat hepatocytes. Hepatocyte function was similarly altered by supernatants from LPS-triggered NPC. Secretory products of macrophages and Kupffer cells (monokines) are possible mediators in this model of cell-mediated modulation of hepatocyte function. In this article, supernatants from NPC capable of altering hepatocyte protein synthesis were found to contain significant amounts of one monokine, interleukin-1 (IL-1). The kinetics of the generation of the ability to inhibit protein synthesis and the appearance of IL-1 activity were roughly parallel for the first 24 hours. Exposure of hepatocytes to NPC supernatant and commercially available highly purified IL-1 resulted in similar response patterns with regard to onset of inhibition and progression of suppression after removal. Certain discrepancies cast doubt, however, on the likelihood that IL-1 is the mediator in this model of cell-mediated inhibition of hepatocyte protein synthesis. Commercial human IL-1 preparations did not always suppress protein synthesis in cultured rat hepatocytes. Furthermore, IL-1 activity was stable for several days but hepatocyte inhibition was lost. Unstimulated peritoneal macrophage supernatants containing IL-1 activity could not inhibit protein synthesis in hepatocytes. The evidence supports the idea that appropriately stimulated cells of monocyte-macrophage lineage (including Kupffer cells that lie in direct apposition to hepatocytes) could mediate hepatocyte malfunction by means of secreted monokines similar to, but not necessarily identical to, IL-1.

Animals↗
PubMed1985

Killed Escherichia coli stimulates macrophage-mediated alterations in hepatocellular function during in vitro coculture: a mechanism of altered liver function in sepsis.

Hepatic dysfunction is a poorly understood and highly lethal component of multiple-system organ failure. Both in vivo and in vitro studies of "liver" function have generally neglected hepatocyte-Kupffer cell interactions. In the following experiments, isolated hepatocytes were cocultivated with unstimulated peritoneal cells, predominately macrophages, which served as a readily available Kupffer cell analog. Coculture of hepatocytes with peritoneal cells resulted in little or no change in [3H]leucine incorporation into hepatocyte protein. When gentamicin-killed Escherichia coli cells (GKEC) were added to coculture, there was a marked decrease in hepatocyte [3H]leucine incorporation. In contrast, GKEC added to hepatocytes alone had no effect. Kinetic data revealed an 8-h delay before any significant decrease in leucine incorporation into hepatocyte protein after the addition of GKEC to the coculture. The maximal decrease in hepatocyte [3H]leucine incorporation occurred 24 h after GKEC were added. The decrease observed 24 h after GKEC were added disappeared almost completely after 48 h of coculture. Similar alterations in cocultured hepatocyte protein synthesis were observed after the addition of phorbol myristate acetate, lipopolysaccharide, or muramyl dipeptide, a component of bacterial peptidoglycan. Hepatocyte viability by trypan blue exclusion was unchanged, and gross morphology by light or electron microscopy was unaffected. We propose that during sepsis, macrophages (Kupffer cells) respond to circulating microbial products and mediate alterations in hepatocyte function. These experiments underscore the important role of Kupffer cell function in attempts to understand hepatic malfunction in multiple-system organ failure.

Animals↗
PubMed1985

Paranasal sinusitis: a common complication of nasotracheal intubation in neurosurgical patients.

Sinusitis secondary to nasotracheal intubation has not been reported to occur in neurosurgical patients. Over a 1-year period, 11 patients admitted to the Intensive Care/Trauma Unit at St. Paul Ramsey Medical Center developed this entity. The mean age of these patients was 36 +/- 4 years; 7 were trauma victims, 3 had each had a subarachnoid hemorrhage, and 1 had suffered hypertensive hemorrhage. The patients presented with fever of unknown origin (FUO) and evidence of persistent hypermetabolism without an obvious cause. In 8 cases, the diagnosis was not suspected until mucopurulent nasal discharge was noted. Three additional cases were evaluated for suspected sinusitis before the occurrence of discharge. The mean duration of intubation before the diagnosis of sinusitis was 7.8 +/- 1.5 days. The diagnosis was confirmed by sinus films with a Waters view in 7 cases or by computed tomographic scanning in 4 cases and by bacteriological cultures. Two cases involved only the maxillary sinus on the side of intubation; the rest were polysinusites. The organisms involved included gram-positive and gram-negative species; all were polymicrobial with a single organism predominant. Secondary pulmonary involvement was common, and 4 patients revealed a bacteremia consistent with the major sinus organism. One patient developed septic shock. Treatment involved either orotracheal intubation or tracheostomy. This was curative in all cases. It is concluded that neurosurgical patients nasally intubated are at risk for sinusitis, which can have untoward effects such as septicemia or pulmonary infection. A high degree of suspicion will permit early diagnosis and treatment.

Adult↗
PubMed1985

Use of a whole blood substitute, Fluosol-DA 20%, after massive postpartum hemorrhage.

Two patients with severe postpartum hemorrhage refused blood product transfusion for religious reasons. The patients' hemoglobin level had dropped to 3.0% or less after operative intervention, and the cardiac indexes on transfer to the tertiary care center were 8.0 and 7.3 L/minute per m2, respectively. Each received an infusion of Fluosol-DA 20% according to research protocol after obtaining informed written consent. Pulse rates and cardiac outputs dropped after the infusions. They were discharged from the hospital 17 and 15 days later with hemoglobins of 7.0 and 5.1%, respectively. Fluosol-DA 20% may be a useful adjunct for therapy of postpartum hemorrhage in women who refuse blood products for religious reasons.

Adult↗
PubMed1985

Efficacy of type-specific and cross-reactive murine monoclonal antibodies directed against endotoxin during experimental sepsis.

To study the role of antibodies in promoting survival during gram-negative bacterial sepsis, we have developed several murine monoclonal antibodies (MAbs). One MAb (5B10) reacted in an enzyme-linked immunosorbent assay with only a single organism (Escherichia coli 0111:B4), while the other (8A1) reacted to all gram-negative whole-cell and lipopolysaccharide (LPS) antigens examined. Either 5B10 MAb, 8A1 MAb, or sterile saline solution was administered intravenously to outbred male Swiss-Webster mice immediately before one of three challenges: (1) viable bacteria intravenously, (2) viable bacteria with hemoglobin intraperitoneally, or (3) intravenous actinomycin D plus LPS. 5B10 MAb provided significant protection against either an E. coli 0111:B4 bacterial or LPS challenge but not against any other organism or type of LPS. 8A1 MAb provided protection against several challenge bacteria (intravenously or intraperitoneally) and against all types of LPS studied except Pseudomonas aeruginosa LPS. A higher dose (2 mg) of cross-reactive antibody (8A1 MAb) was required to produce protection when compared with the type-specific protection produced with 5B10 MAb (0.1 mg). Although ideal antibody therapy would consist of directing a specific MAb against a single microorganism, the acute nature of the disease process and time required to prepare reagents may preclude the use of type-specific MAbs. We believe that the cross-reactive and cross-protective capacity of 8A1 MAb or a similar MAb may be useful in averting the lethal effects of clinical gram-negative bacterial sepsis and warrants testing in the clinical setting.

Animals↗
PubMed1985

Hepatocyte function in sepsis: Kupffer cells mediate a biphasic protein synthesis response in hepatocytes after exposure to endotoxin or killed Escherichia coli.

Alterations in hepatic function are seen in sepsis and/or multiple system organ failure. We hypothesized that Kupffer cells (KC) within the liver may mediate functional alterations in adjacent hepatocytes (HC) in response to bacterial products. We have previously described decreases in rat HC protein synthesis during in vitro cocultivation with peritoneal macrophages in the presence of gentamicin-killed Escherichia coli (GKEC) or endotoxin (LPS). The present studies demonstrate that purified (greater than 95%), syngeneic, or allogeneic KC exposed to GKEC or LPS impart a biphasic response in cultured HC. When HC were cultured alone there was no alteration in 3H-leucine incorporation into HC protein after the addition of GKEC or LPS. When HC were cocultured with KC there was increased protein synthesis compared with HC alone (p less than 0.001). After the addition of GKEC or LPS there was an immediate increase in coculture HC protein synthesis. However, a marked decrease in coculture protein synthesis was seen 16 degrees later (p less than 0.001). To ensure that KC alone were responsible, splenic lymphocytes were added to HC alone or HC/KC coculture, but they did not alter the results. HC viability and appearance were unchanged throughout the experiments. These results show that exposure of KC to microbial products can profoundly alter HC function and support the concept of local KC modulation of HC function during sepsis.

Animals↗
PubMed1985

The systemic septic response: multiple systems organ failure.

Sepsis, which is the host response to one or more microorganisms, is probably best understood within the concept of activator-mediator-responder. The various forms of metabolic support work in all three areas. The best treatment is still prevention. The mortality rate has progressively fallen and is now in the range of 35 to 40 per cent. Appropriate nutritional support seems to have been an important factor in this reduction in mortality. There are many new areas of research that need to be evaluated, and many of these areas are now directed at regulatory aspects of the metabolic response.

Animals↗
PubMed1985

Enteral feeding in sepsis: a prospective, randomized, double-blind trial.

In an attempt to meet better the needs of patients with hypermetabolic stress, amino acid formulas have been modified (MAA). As part of a total parenteral nutrition regimen, MAA have been associated with improvement in parameters of nutrition and survival. The safety and efficacy of these formulas in balanced enteral nutrition was assessed in malnourished patients with moderate to high levels of stress undergoing surgery. The nutritional targets were 5 gm/kg/day glucose, 0.8 gm/kg/day fat, and 0.27 gm/kg/day amino acid nitrogen. In an initial nine studies, the MAA nutrition was safe even in the presence of ileus. A double-blind, randomized, prospective trial was then undertaken in 18 patients in an isocaloric, isonitrogenous design with the nitrogen source as MAA (44% branched-chain amino acids) or standard amino acids (28% branched-chain amino acids). The patients receiving MAA had enhanced nitrogen retention, visceral protein mass, and indices of survival.

Adolescent↗
PubMed1985

Multiple systems organ failure. Modulation of hepatocyte protein synthesis by endotoxin activated Kupffer cells.

The etiology of hepatic insufficiency associated with the multiple systems organ failure (MSOF) syndrome is unclear. The authors have investigated the possibility that a macrophage/Kupffer cell mediated modulation of hepatocyte function may play a role in this phenomenon. Isolated rat hepatocytes were cultured, and their rate of protein synthesis was measured by cpm of 3H leucine incorporation into protein. Nonparenchymal rat liver cells (NPC) comprised of 35-40% Kupffer cells were added to hepatocytes to establish a co-culture with or without endotoxin. Neither NPC alone nor endotoxin alone affected hepatocyte protein synthesis. However, in the presence of endotoxin, NPC caused a marked diminution of hepatocyte protein synthesis (4,396 +/- 449 cpm) compared with control hepatocytes (10,943 +/- 623 cpm). No change in microscopic morphology or ability to exclude trypan blue occurred. This modulation of hepatocyte function by an endotoxin stimulated Kupffer cell preparation may, in part, represent the mechanism of hepatic insufficiency associated with the MSOF syndrome.

Animals↗
PubMed1985

Alterations in amino acid clearance during ischemia predict hepatocellular ATP changes.

Although decreases in hepatic adenosine triphosphate (ATP) levels during ischemia are thought to reflect loss of hepatic energy reserves and decreased viability, such changes have not been correlated with a clinically relevant index of hepatic function or viability. Ability to clear amino acids from plasma has been shown to correlate with function of the allograft in hepatic transplantation and survival after portal decompression in patients with hepatic cirrhosis. The effects of 60 minutes of warm ischemia in two groups of mongrel dogs were studied to assess the relationship between loss of ATP and amino acid clearance. One group (shunted) had portal decompression during the ischemic period and the other (portal stasis) did not. There was a significant correlation between loss of ATP and amino acid clearance after ischemia. Although the effects of ischemia on the liver were similar in both groups, the portal stasis group demonstrated significantly elevated SGOT levels during reperfusion that were related to impaired net adenine monophosphate synthesis and suggestive of ongoing injury. These data support the contention that loss of ATP during ischemia is associated with reduced functional capacity. In addition, they suggest that portal stasis produces toxic products that can impede hepatic recovery from ischemia.

Adenosine Triphosphate↗
PubMed1984

Branched chain metabolic support. A prospective, randomized, double-blind trial in surgical stress.

A prospective, randomized, double-blind trial of the nutritional effects of branched chain modified amino acid solutions was undertaken in 23 surgical patients within 24 hours of the onset of major general surgery, polytrauma, or sepsis. The effects were evaluated in the absence of abnormalities of oxygen transport and perfusion in an isocaloric/isonitrogenous setting where the major difference between the groups was the amount of branched chain amino acids received. Both groups received balanced parenteral nutrition with 1.5 gm/kg/day of amino acids, 30 calories/kg/day of glucose, and 7 calories/kg/day of fat. At the end of the 7-day study interval, the group receiving the branched chain enriched therapy at 0.7 gm/kg/day of branched chain amino acids had improved nitrogen retention; an elevation of their absolute lymphocyte count from 800 to 1800/mm3, a reversal of anergy to recall skin test antigens in 60% of the patients, and improved plasma transferrin levels (p less than 0.03). Nutritional support using the modified amino acid metabolic support solutions has beneficial effects during the stress interval that do not seem as achievable with current commercially available nutritional support regimens.

Adult↗
PubMed1984

Use of a needle valve variable resistor to improve invasive blood pressure monitoring.

Inaccurate measurements using in-line systems are partly due to the resonance frequency. A variable acoustic resistor designed to change the damping coefficient of these monitoring systems was evaluated under clinical conditions. The device improved pressure transmission characteristics in measurements on 12 of 13 patients. Use of the device and of the bedside step-impulse test for calibration should improve the reliability of in-line blood pressure monitoring.

Blood Pressure Determination↗