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Biomedical subjects

F B Cerra

Publications and source records attributed to F B Cerra.

At least 163 records · Page 9Linked to original sources
PubMed1984

Quantitative evaluation of clinical course in surgical ICU patients: the data conform to catastrophe theory.

A response surface for critically ill patients is described. The coordinates of the three-dimensional response surface are two control variables, or state variables, related to aerobic and anaerobic metabolism, and a response variable, the A-VO2 difference. The data conform to a cusp catastrophe manifold. Cardiac insufficiency, adaptive response to stress, and sepsis may be distinguished by this model. The distinction between control and response variables is discussed.

Aerobiosis↗
PubMed1984

Mechanism of arginine protection against ammonia intoxication in the rat.

To examine the beneficial effect of arginine on ammonia intoxication, rats were injected intraperitoneally with a single dose of NH4Cl (6.75 mmol/kg) with and without arginine (5.0 mmol/kg) or ornithine (5.0 mmol/kg). Arginine or ornithine reduced the blood ammonia nitrogen at 30 min after NH4Cl injection from 3,288 +/- 800 micrograms/dl (mean +/- SE) to 538 +/- 90 and 575 +/- 34 micrograms/dl, respectively. In rats administered this dose of NH4Cl, arginine or ornithine did not increase further the hepatic carbamoyl-phosphate synthetase (EC 6.3.4.16) activation by N-acetylglutamate beyond the effect of NH4Cl. However, arginine or ornithine did increase the hepatic citrulline and urea content as well as the plasma urea concentration in these NH4Cl-injected rats. In rats injected with four doses of NH4Cl (2.5 mmol/kg), arginine or ornithine pretreatment increased the urea excretion and normalized the orotic acid excretion. These results indicate that arginine mitigates ammonia intoxication in the rat by increasing ornithine carbamoyltransferase activity through increased ornithine availability and not via activation of N-acetylglutamate synthetase. By increasing ornithine carbamoyltransferase activity, ornithine enhances the conversion of ammonia to citrulline and urea.

Acetyltransferases↗
PubMed1984

The therapy of anaphylactic shock.

Anaphylaxis is an acute, often life-threatening systemic reaction to mediators released by basophils and mast cells. Histamine, leukotrienes, prostaglandins, and other mediators are responsible for complex and varied reactions in man. Serious cardiovascular or pulmonary involvement can lead to death within minutes. Therapy depends on prompt recognition of the disease and rapid administration of epinephrine. Even in ideal clinical settings, response to therapy may be slow and a long resuscitation necessary. Antihistamines, glucocorticoids, intravascular volume expansion, sympathomimetics, bronchodilators, and controlled ventilation all may be necessary. Taking careful allergy histories; using enteral routes for drug administration when possible; observing patients, who have received injections for at least 20 minutes; and rapidly treating patients with epinephrine are the main means of reducing the incidence and mortality of this disease.

Anaphylaxis↗
PubMed1984

Anticore endotoxin F(ab')2 equine immunoglobulin fragments protect against lethal effects of gram-negative bacterial sepsis.

Gram-negative bacterial sepsis and shock remain a cause of substantial morbidity and mortality in hospitalized patients despite appropriate antimicrobial therapy, fluid resuscitation, and monitoring. We sought to test the ability of equine antibody directed against core endotoxin, a portion of bacterial outer membrane lipopolysaccharide common to many gram-negative microorganisms, to bind to various gram-negative bacteria in vitro, to promote bacterial phagocytosis by leukocytes, and to protect against lethal gram-negative bacteremia in mice. The importance of the IgG Fc leukocyte attachment site was examined by comparing the ability of intact IgG and IgG F(ab')2 fragments to protect against lethality during murine sepsis. A single horse was immunized with Escherichia coli J5, an organism that expresses a portion of core endotoxin extensively on the cell surface. Preimmunization IgG and F(ab')2 possessed no titer as determined by enzyme-linked immunosorbent assay, did not promote in vitro phagocytosis, and did not protect in vivo. Postimmunization IgG and F(ab')2 possessed a significant titer to E. coli J5 whole cell and lipopolysaccharide antigens and provided significant (p less than 0.05) protection in vivo during lethal intravenous sepsis caused by either E. coli J5, E. coli 0111:B4, Klebsiella pneumoniae, or Pseudomonas aeruginosa. Only postimmunization IgG, but not F(ab')2, promoted in vitro phagocytosis of these same organisms. We therefore hypothesized that protection occurred as a result of antitoxin activity rather than opsonization and phagocytosis, as F(ab')2 fragments were as active as the intact molecule. Further studies must be done to determine the role of anticore endotoxin antibody in conjunction with antibiotics so that appropriate clinical studies may be undertaken.

Animals↗
PubMed1984

Metabolism during hepatic transplantation: indicators of allograft function.

In an attempt to determine the initial function of hepatic allografts, several metabolic indicators of hepatic function were studied intraoperatively in 12 cases of hepatic transplantation. The operation was divided into three sampling periods: baseline, anhepatic, and reperfusion. During the baseline period plasma lactate levels rose at 2.6 mmol/L/hr and continued to rise at a similar rate during the anhepatic period. Baseline period total free plasma amino acid levels (TFPAA) rose at a moderate rate of 0.4 mmol/L/hr. During the anhepatic period TFPAA levels rose at a fivefold greater rate than during baseline (p less than 0.01). The ability of the hepatic allograft to reduce abnormal levels of TFPAA and lactate during the reperfusion period was associated with reduced morbidity in the first 48 hours after transplantation. Intraoperative clearance of accumulated TFPAA is currently the best means of assessing initial allograft function. Elevated preoperative total serum bilirubin levels were also associated with increased early morbidity in hepatic transplant recipients.

Adult↗
PubMed1984

Effects of parenteral and enteral hyperalimentation on hepatic drug metabolism in the rat.

Whereas patients receiving parenteral hyperalimentation frequently have abnormalities in serum liver enzymes, the influence of i.v. administration of hypertonic glucose-protein solutions on hepatic function has received little attention. Recent data from this laboratory indicated that in vivo clearance of pentobarbital was significantly decreased in rats receiving total parenteral hyperalimentation (TPN) vs. animals receiving the same hyperalimentation solution enterally (total enteral hyperalimentation; TEN). To determine the cause of this decreased clearance, we have analyzed mixed-function oxidase activity in hepatic microsomes prepared from livers of rats receiving 7 day continuous i.v. or i.g. infusions of hypertonic glucose (25%) combined with fibrin hydrolysate or crystalline amino acids. Hepatic microsomal cytochrome P-450 and capacity for demethylation of meperidine and hydroxylation of pentobarbital were significantly reduced in TPN animals as compared to TEN and ad libitum chow-fed control rats. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of microsomal protein revealed increased staining of a 46,500 molecular weight band and decreased intensity of a 52,700 molecular weight band in TPN experiments as compared to TEN studies. Increasing amino acid concentration in infusions to 4.25% from the standard 2.75% resulted in marked reductions in hepatic microsomal drug metabolism in enterally hyperalimented animals. These studies show that the route of alimentation delivery has an important influence on hepatic drug metabolic function in rats and suggest that quantitative and/or qualitative differences in hepatic delivery of protein may be responsible for the quantitative and qualitative differences in hepatic microsomal mixed-function oxidases observed between TPN and TEN animals. If similar changes occur in humans receiving TPN, major alterations in drug regimens may be required.

Amino Acids↗
PubMed1983

The role of heparin in guinea pig gram negative bacterial sepsis.

The ability of antibody directed against shared antigenic determinants of gram negative organisms to protect against a challenge of diverse gram negative bacterial species remains controversial in the experimental setting. Attention has focused, however, on the use as immunogens of rough mutants of Escherichia coli and Salmonella minnesota, which express a portion of core lipopolysaccharide (LPS) extensively on their cell surface. Core LPS is a structure present on the outer membrane of most, if not all, gram negative bacteria. In this study rabbits were immunized with E. coli J5, a rough mutant of E. coli, to produce anti-E. coli J5 rabbit antiserum (anti-J5 RS). Anti-J5 RS was found to cross react extensively by enzyme-linked immunosorbent assay with various gram negative bacterial whole cell or LPS antigens, compared to normal rabbit serum (NRS). Anti-J5 RS +/- heparin was also compared to NRS +/- heparin pretreatment in a guinea pig model of sepsis utilizing E. coli O111:B4 as the challenge organism. Anti-J5 RS +/- heparin augmented systemic bacterial clearance compared to NRS +/- heparin, but only the combination of anti-J5 RS and heparin enhanced survival 48 hr after bacterial challenge. It was concluded that pretreatment with anti-J5 RS was a necessary, but not sufficient condition for enhanced survival, and that the addition of heparin to anti-J5 RS pretreatment might diminish the otherwise lethal consequences of complement activation and disseminated intravascular coagulation in this model system.

Animals↗
PubMed1983

Nitrogen retention in critically ill patients is proportional to the branched chain amino acid load.

The nitrogen retention effect of branched chain enriched parenteral nutrition (BcAA) during surgical stress and polytrauma was evaluated in a prospective, randomized, double blind study in 32 patients. The doses of BcAA were 0.16, 0.3, 0.5, and 0.7 g/kg . day with a total amino acid load of 1 or 1.5 g/kg . day. It was provided in a setting of 30 glucose cal/kg . day with 7 cal/kg . day of iv fat also given to 16 patients. After the 7-day study was completed, analysis of the 4 treatment groups of 8 patients each demonstrated that there was an increased nitrogen retention effect of BcAA, that the effect was proportionate to BcAA load, that the effect started at 0.5 g of BcAA/kg . day in a setting of balanced nutritional support, and that the effect was consistent with a BcAA influence on protein synthesis. There were no complications or side-effects from high dose BcAA. Metabolic support of the stress response in ICU patients has become a clinical reality.

Adult↗
PubMed1983

Cirrhosis, encephalopathy, and improved results with metabolic support.

Twenty-two patients with cirrhosis and acute encephalopathy who were refractory to medical therapy were entered into a randomized, double-blind prospective trial. This trial consisted of either neomycin or a modified amino acid solution rich in branched chains and low in aromatic amino acids and methionine (F080) in the presence of isocaloric amounts of dextrose. The groups were indistinguishable from each other by clinical or laboratory criteria; they were primarily patients who had undergone operation and they would tolerate only 30 gm of oral protein or intravenous standard amino acids. The group receiving F080 had a faster and more complete improvement in encephalopathy. This improvement correlated with the plasma molar ratio and occurred with a lower mortality rate. In addition, the patients also tolerated twice the amino acid load without encephalopathy and were in positive nitrogen balance. Modified metabolic support is effective in the setting of acute liver failure in chronic cirrhosis, particularly in patients who have undergone operation.

Adolescent↗
PubMed1983

Peripheral postcapillary venous pressure: a new, more sensitive monitor of effective blood volume during hemorrhagic shock and resuscitation.

Peripheral postcapillary venous pressure (PCVP) and mixed venous oxygen saturation (SvO2 or PASO2) have been shown to be sensitive indicators of volume status and appear to reflect the adequacy of peripheral perfusion during controlled bleeding. This study demonstrates that in an open-chest dog model with controlled venous return, PCVP is closely and linearly (r2 = 0.6) correlated with cardiac output (CO). Furthermore, oxygen saturation as measured in the central venous system (CVSO2) and peripheral vein PVSO2) were found to be closely and linearly related to PASO2 (r = 0.72 to 0.99 and 0.91 to 0.98, respectively). Thus PCVP, CVSO2, and PVSO2 represent easily and safely obtainable parameters that closely reflect major physiologic variables. During resuscitation after controlled hemorrhage, the PCVP and PVSO2 accurately reflected the restoration of blood volume and were as good as CO and central saturations. Central venous and pulmonary wedge pressures both poorly reflected the return to full volume repletion (P less than 0.01). Thus, PCVP and PVSO2 seem to be reliable indices of volume status and perfusion and do not require invasive, central monitoring.

Animals↗
PubMed1982

Pathologic synergy in cardiovascular and respiratory compensation with cirrhosis and sepsis. A manifestation of a common metabolic defect?

Multivariable physiologic studies of cardiovascular, respiratory, and metabolic functions were performed in 341 patients (884 studies). Eighty patients had cirrhotic liver disease, 64 had sepsis, 87 had nonseptic cariogenic syndromes, and 110 had nonseptic general surgical or traumatic injury. The group with cirrhosis had the highest cardiac index and ejection fraction. When compared with the group with nonseptic surgery or trauma, vascular tone was reduced in the patients with cirrhosis or sepsis and was lowest in patients with both conditions. Ventricular function was good in the groups with cirrhosis or sepsis, due to the additive effect in reducing vascular tone that allowed ejection fraction to increase, but caused the ratio of alveolar ventilation to perfusion (VA/QT) to fall, resulting in a greater perfusion of a decreased pulmonary vascular bed. The falls in vascular tone and VA/QT in patients with cirrhosis or sepsis result from the reduced oxygen consumption that occurs due to metabolic imbalance (B state). This B state seems to reflect a hepatic inability to metabolize aromatic amino acids, so that levels of tyrosine, phenylalanine, and the false neurotransmitter octopamine increase. These mechanisms are pathologically synergistic when sepsis and cirrhosis occur together.

Amino Acids↗
PubMed1982

Mental status, the intensive care unit, and cimetidine.

A blinded, prospective study of the association between cimetidine treatment and altered mental status (MS) was evaluated in 217 surgical intensive care patients stratified by the degree of renal or hepatic dysfunction or both. The cimetidine and noncimetidine groups did not differ in blood chemistries, physiologic-metabolic data, or concurrent medications. There was a correlation between treatment with cimetidine and changes in MS (p less than 0.0001). The MS changes with cimetidine ranged from 33% for neither hepatic nor renal dysfunction to 80% for both renal and liver impairment. The magnitude of MS change was influenced by disease and serum concentration, with patients with both renal and liver disease having the greatest MS change at the highest serum concentrations. The type of MS change was also disease specific. All MS change cleared within 24 to 36 hours of stopping the drug. It appears that both dosage and underlying disease state are important factors determining the nature and severity of cimetidine-associated mental status changes.

Adult↗
PubMed1982

Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients.

We studied 201 critically ill patients during 267 courses of gentamicin (139 courses) or tobramycin (128 courses) therapy. Clinical and pharmacokinetic data were obtained on 240 of 267 courses (120 courses each of gentamicin and tobramycin). Two judgments of nephrotoxicity and its cause were made independently in this study, using a clinical and a pharmacokinetic definition of nephrotoxicity. The two sets of criteria were generally in good agreement, as all but 10 of 41 patients who were judged nephrotoxic by pharmacokinetic criteria were independently judged nephrotoxic by the clinical definition. Groups of patients judged nontoxic did not differ from groups judged nephrotoxic in age, sex, weight, initial creatinine clearance, total dose given, duration of treatment, initial aminoglycoside trough serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Prior aminoglycosides (usually gentamicin) had been used more frequently in the nontoxic group (P less than 0.05). Two major conclusions of this study are at variance with those of previous investigators; (i) we found no clinical parameters of value in predicting nephrotoxicity in critically ill patients; and (ii) aminoglycoside serum concentrations, once in the therapeutic range, were of limited value in prevention of aminoglycoside nephrotoxicity in our patients.

Aminoglycosides↗