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F B Cerra

Publications and source records attributed to F B Cerra.

At least 127 records · Page 7Linked to original sources
PubMed1987

Overcoming retention time shifts as a source of error in HPLC analysis.

When used for physiologic fluid analysis, shifts in retention times, even at constant flow rates, can cause integrators to function inadequately as tools for peak identification and thus result in concentration errors. A system capable of data collection, identification, quantification, and long-term storage that primarily uses retention times only for identification of elution sequence is described. Operator identification, aided by manipulation of x and y coordinates of the chromatograph, enhances positive identification of compounds for the experienced chromatographer.

Amino Acids↗
PubMed1987

Essential fatty acid status in isolated closed head injury.

Abnormal profiles of polyunsaturated fatty acids in the plasma phospholipid fraction were observed in 14 patients with hypermetabolism due to severe isolated closed head injury. Depressed linoleic acid levels were observed within 24 hours along with elevation of oleic acid levels. By one week postinjury, subnormal levels of arachidonic acid were also observed. These data indicate that the metabolic response to injury encompasses changes in the metabolism of polyunsaturated fatty acids which are rapid in onset and qualitatively similar to those seen in mild essential fatty acid deficiency.

Adult↗
PubMed1987

Left ventricular function in malnutrition.

Twenty-one dogs were chronically instrumented with ultrasonic left ventricular dimension transducers and micromanometers to elucidate the effects of acute protein-calorie malnutrition on cardiac function. Ten dogs received a regular diet for 3 wk, whereas 11 dogs received a protein-calorie-deficient diet designed to achieve a mean weight loss of 20-25% over a 3-wk period. Studies of cardiac function were performed in awake intact animals at base line (1 wk postoperatively) and after 3 wk. In the malnourished dogs, cardiac mass was lost in proportion to total body mass loss. Mean cardiac mass fell from 115 to 91 g. This was largely due to wall thinning in this group. Heart rate dropped from 125 to 79 beats/min with malnutrition and ejection fraction increased from 29.8 to 34.6%. Cardiac output fell from 2.98 to 2.38 l/min, but cardiac index normalized to body surface area was unchanged. No significant changes in hemodynamics were observed in the control group. In the malnutrition group, global ventricular contractility, as measured by the load-independent index of systolic function or the slope of linear relationship between end-systolic pressure and end-systolic volume (EmaxPV), decreased slightly from 3.56 to 2.81 mmHg/ml (P = 0.07). However, Emax calculated from circumferential stress and strain data was unchanged. This indicates that depressed contractility was due to loss of cardiac muscle mass rather than any change in the myocardium per se. Response to beta-adrenergic stimulation was unchanged with starvation. Acute protein-calorie malnutrition causes significant cardiac atrophy that is reflected in decreased cardiac output and slightly reduced contractility but not in intrinsic properties of the myocardium.

Animals↗
PubMed1987

Physiological and metabolic response to isolated closed-head injury. Part 2: Effects of steroids on metabolism. Potentiation of protein wasting and abnormalities of substrate utilization.

In order to determine the effects of steroid administration on the metabolic response to isolated closed-head injury, a longitudinal study was performed. Metabolic indices were prospectively evaluated for the first 5 days postinjury in six patients who received steroids and 10 patients who did not. Patients were carefully screened to eliminate those with associated injuries as well as those with abnormalities due to sepsis. Other than steroid administration, a uniform treatment regimen was used in both groups. Metabolic indices measured on postinjury Days 1, 3, and 5 were analyzed. In addition, data were compared to results in large data banks obtained both from overnight-fasted patients (fasted controls) and from polytrauma victims (stressed controls). Both treatment groups were comparable with respect to age, mean Glasgow Coma Scale scores on admission and on Day 5, and initial intracranial pressure. Metabolic data indicated significantly higher levels of nitrogen excretion and somatic protein mobilization in steroid-treated patients than in patients not receiving steroids. In both groups, glucose levels, the lactate/pyruvate ratio, and branched-chain amino acid levels (all metabolic indices that correlate well with level of stress) initially corresponded to values for stressed controls. By Day 5, values for these variables were similar to fasted controls for the group not receiving steroids. In patients receiving steroids, however, the data remained similar to those for stressed controls. It is concluded that steroids prolong the metabolic abnormalities associated with the initial phase of head injury. In view of inconclusive data regarding benefit from steroid administration, serious questions must be raised regarding the use of these catabolic agents in this setting.

Adult↗
PubMed1987

Nutrition support of the adult liver transplant candidate.

Liver transplantation now provides a viable alternative to patients with end-stage hepatic failure. Because of the damaging effects of liver failure on other organ systems, transplant candidates frequently suffer from moderate to severe malnutrition. Chronic hepatic failure can result in deranged metabolism of not only macronutrients and micronutrients but also various hormones. Patients are frequently in a catabolic state. Wasting of the skeletal muscle mass occurs and synthesis of secretory proteins and clotting factors decreases. Hepatic encephalopathy and fluid/electrolyte imbalances often complicate the provision of appropriate nutrition support. Nutrition support may be provided by the oral route, tube feeding, parenteral nutrition, or a combination of those routes. A multidisciplinary approach to determine the appropriate nutrition support regimen is most optimal. To assess the efficacy of the support, monitoring of the nutritional/metabolic status is necessary on an ongoing basis. An aggressive nutrition support regimen can induce positive nitrogen balance, promote hepatic protein synthesis, and expand lean body mass, controlling the symptoms of malnutrition in end-stage liver disease.

Adult↗
PubMed1987

Hypermetabolism, organ failure, and metabolic support.

The hypermetabolism organ failure complex remains the predominant reason for both prolonged stay and death in the surgical intensive care unit. What was perceived as isolated organ failure, such as adult respiratory distress syndrome, is now seen as part of the systemic response to injury and repair. Sepsis has become the systemic inflammatory response due to invading microorganisms. What was once perceived as diagnostic of sepsis has been recognized after severe perfusion deficits and in the presence of continuing sources of dead and injured tissue. The transition to organ failure is usually a distinct clinical event and probably represents the onset of clinical hepatic failure. Once present, the organ failure syndrome has a high mortality rate. From a treatment perspective, it is recognized that there is probably no "magic bullet"; that regimens will probably be time dependent and "multiple drug"; and that the best treatment is prevention. Malnutrition, as opposed to changes in body composition that occur as a result of disease process, has become a recognized cofactor in morbidity and death in patients with persistent hypermetabolism and organ failure. The metabolic processes of hypermetabolism have become increasingly categorized and understood. The result has been the development of metabolic support principles that are distinct from those of nutritional support and are designed to prevent the end-organ changes of malnutrition and the development of substrate-limited metabolism, to support organ structure and function, and to attempt to arrest the metabolic processes. The initial problem was to learn to do no harm, an outcome reasonably achieved. In addition, several beneficial results have been recognized including new techniques to better support total body protein synthesis, hepatic protein synthesis, and energy production. Techniques to better support organ structure and function are being tested. No techniques are currently available to control proteolysis and the redistribution of skeletal muscle nitrogen. A great deal of research is still necessary in this field, which is still in its infancy.

Energy Metabolism↗
PubMed1987

Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis.

The pharmacokinetic disposition of aminoglycosides in critically ill patients with sepsis was studied. In an open-label study of the disposition of gentamicin and tobramycin, individualized pharmacokinetic values of 100 critically ill patients in the surgical intensive-care unit were compared with those of a concurrently monitored group of 100 surgery patients who were not critically ill. The a priori computer-predicted dosage requirements of the critically ill patients were also compared with the dosages derived from their individualized pharmacokinetic values, and intrapatient variation in the critically ill patients was studied. Serum concentration-time data were analyzed using a one-compartment model and the DataMed Clinical Support Services system to provide individualized dosage requirements. Initial dosing guidelines were also generated for the critically ill patients using the a priori model of the DataMed Clinical Support Services program and patient demographic information. The critically ill patients were significantly older, had higher serum creatinine concentrations (SCr), and had lower elimination rate constants (k) and total body clearances (CL) than the surgery patients who were not critically ill. The volume of distribution (V) was not significantly different. The a priori computer predictions for the critically ill patients were significantly lower than the individualized values for V, CL, dose, and amount of drug per 24 hours. The dosing regimen from the a priori model was the same as the individualized regimen in only 2/100 patients. In the 76 critically ill patients who had a second pharmacokinetic analysis performed, there was a significant decrease in k and CL from the first analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Decreased hepatic clearance of clindamycin in critically ill patients with sepsis.

Clindamycin pharmacokinetics was compared in critically ill patients with sepsis and healthy volunteers, and the relationship between pharmacokinetic values and physiological measurements obtained from the critically ill patients was characterized. Pharmacokinetic evaluations were performed on 10 patients with sepsis who were receiving clindamycin phosphate 900 mg i.v. every eight hours and on 6 previously studied healthy men receiving the same dosage regimen. Physiological variables measured included age, weight, cardiac index, systemic vascular resistance, central venous pressure, liver-function tests, alpha 1-acid glycoprotein concentration, and APACHE II score. Clindamycin was administered to the critically ill patients via a central venous catheter over 30 minutes; the healthy volunteers received their infusions via a peripheral venous catheter over 30 minutes. Blood samples were obtained at five minutes before and at various intervals after drug administration. Serum clindamycin concentrations were determined by a gas-liquid chromatographic method. Serum concentration data were analyzed using noncompartmental methods based on statistical moment theory, and the a priori level of significance was 0.05. The critically ill patients had significantly increased values for area under the curve (AUC), area under the moment curve (AUMC), mean residence time (MRT), and average concentration at steady state (Css), while total body clearance (TBC) was less than half that in the healthy volunteers. TBC in three of the critically ill patients was not different from that in the healthy volunteers. The apparent volume of distribution at steady state (Vss) was not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Immunotherapy of gram-negative bacterial sepsis. A single murine monoclonal antibody provides cross-genera protection.

Previous experimental and clinical studies have demonstrated the ability of polyclonal antibody directed against the core lipopolysaccharide (LPS)-lipid A component of endotoxin to reduce mortality. We sought to characterize the ability of a single murine monoclonal IgG1 antibody (8A1 MAb) to react to a variety of gram-negative microorganisms, to promote phagocytosis, and to provide protection during experimental murine sepsis. The 8A1 MAb reacted to various gram-negative bacterial whole cell and LPS antigens examined by enzyme-linked immunosorbent assay. Reactivity was highest to Salmonella minnesota Re LPS and lipid A. Phagocytosis was promoted by this monoclonal antibody to several gram-negative bacteria, except Pseudomonas aeruginosa. The 8A1 MAb (2 mg per mouse) enhanced survival during bacteremia due to either Escherichia coli 0111:B4 or Klebsiella pneumoniae, and during endotoxemia due to all types of LPS examined except P aeruginosa. We concluded that a single MAb with anti-lipid A specificity was cross reactive in vitro and cross protective in vivo. A clinical trial comparing polyclonal and monoclonal antibody in high-risk septic patients seems warranted.

Animals↗
PubMed1986

Macrophage-mediated modulation of hepatocyte protein synthesis. Effect of dexamethasone.

We have previously reported an in vitro model demonstrating decreased hepatocyte protein synthesis following co-culture with macrophage-rich peritoneal cells (MRPC) in Sprague-Dawley rats. These observations have been proposed by us and others to represent a possible model for macrophage- or Kupffer cell-mediated modulation of hepatocyte function. Such a mechanism may play a role in the etiology of hepatic failure in sepsis. This effect is shown in this investigation to be completely blocked by dexamethasone at concentrations equal to or greater than 10(-9) M. The presence of lymphocyte-activating factor in the MRPC-conditioned medium is suppressed at the same concentration of dexamethasone. Resident MRPC were shown to secrete significant amounts of lymphocyte-activating factor activity without further in vitro activation. These results support the concept that the MRPC mediation of decreased hepatocyte protein synthesis is inflammatory in nature and possibly associated with macrophage activation.

Animals↗
PubMed1986

Physiological and metabolic response to isolated closed-head injury. Part 1: Basal metabolic state: correlations of metabolic and physiological parameters with fasting and stressed controls.

Studies of the metabolic and physiological response to closed-head injury have intimated the presence of persistent hypermetabolism. To more fully define and evaluate the metabolic response to head trauma, a prospective study was conducted in patients with isolated closed-head injuries. Metabolic and cardiopulmonary data were obtained for a 7-day period. Patients with multiple injuries or infections, or those who received steroids, were excluded. The basic treatment regimen utilized hyperventilation, bed rest with head elevation, intracranial pressure monitoring, mild fluid restriction, and mannitol as needed. No exogenous nutritional support was given. Intrastudy trends and comparsion with data from unstressed fasting patients and stressed patients were noted. Mean Glasgow Coma Scale scores were 4.4 +/- 1.5 initially, but rose to a mean of 8.2 +/- 3.7 by Day 7. While the responses of cardiac index, CO2 production, lactate/pyruvate ratio, and arteriovenous O2 content difference (AVO2D) were initially elevated, these parameters declined over the course of 7 days. The AVO2D was equivalent to the fasting level by Day 5. Metabolic data, including most amino acid levels in plasma, showed an initial equivalence to stress control levels and a pattern similar to that in non-stressed control subjects by Day 7. Nitrogen and 3-methyl histidine excretion were persistently elevated for the full 7 days. Patients with isolated closed-head injury seemed to be initially hypermetabolic, but this process appeared to resolve by 1 week; the persistent nitrogen excretion may reflect equilibration of muscle mass to the existing level of activity (bed rest). After the first few days, nitrogen excretion may give an erroneous index of the level of metabolic stress and the type or amount of nutritional support needed.

Adolescent↗
PubMed1986

Partial correction by exogenous lipid of abnormal patterns of polyunsaturated fatty acids in plasma phospholipids of stressed and septic surgical patients.

Polyunsaturated fatty acid (PUFA) profiles are abnormal in a variety of clinical conditions that are commonly seen in the surgical intensive care unit. PUFA profiles in the serum phospholipids were studied by capillary gas chromatography in 22 critically ill, hypermetabolic surgical intensive care unit patients. All patients received continuous total parenteral nutrition (TPN) by central vein with trace elements and vitamins. Eleven patients received daily supplementation with 50 gm of safflower oil-based lipid emulsion (TPN + L group). No lipid was administered in the other 11 patients (TPN). Both groups showed deficiencies in 18:2 omega 6 linoleic acid from the time of onset of TPN. In TPN the deficiency was progressive; in the TPN + L group, lipid administration prevented this progression but did not restore 18:2 omega 6 levels to normal. In the TPN group levels of 18:1 omega 9 and its metabolite 20:3 omega 9 (the triene of deficiency) increased over time, consistent with a mild essential fatty acid deficiency. These changes in omega 9 acids were not seen with lipid supplementation. Despite low levels of 18:2 omega 6 in both groups, the levels of omega 6 metabolites were normal or increased. Levels of 20:4 omega 6 (arachidonate) remained normal or slightly decreased in the TPN group but were decreased in the TPN + L group. Levels of arachidonate metabolites, in particular 22:5 omega 6, were increased in the lipid-supplemented group. We concluded that stressed patients receiving TPN develop mild essential fatty acid deficiency that is only partially correctable by lipid supplementation and that administration of supplemental lipid to these patients stimulates arachidonic acid conversion to 22:5 omega 6.

Aged↗
PubMed1986

The role of nutrition in the management of metabolic stress.

The metabolic response to injury is a different process from starvation. As such, it requires a different set of nutritional support principles in order to provide effective therapy that is cost-conscious and with a minimum of complications. In all cases, it is essential to restore and to maintain oxygen transport prior to instituting nutritional support. In the higher levels of stress, an enhanced response can be achieved with the modified amino acid formulas in a setting of balanced nutritional support. With the principles outlined above, nutritional status can be effectively managed in most settings as a variable that influences morbidity and mortality in surgery, polytrauma, and sepsis.

Amino Acids↗
PubMed1986

Further characterization of Kupffer cell/macrophage-mediated alterations in hepatocyte protein synthesis.

Alterations in hepatic function are seen in sepsis or multiple-system organ failure. We have hypothesized that Kupffer cells (KCs) within the liver alter the function of contiguous hepatocytes after exposure to septic stimuli. Using an in vitro coculture system, we have found that lipopolysaccharide (LPS) induced a 40% to 60% decrease in cocultured hepatocyte protein synthesis but had no effect on hepatocytes alone. Coculture in the absence of LPS resulted in enhanced hepatocyte protein synthesis proportional to the number of KCs or macrophages (M0s). Conditioned medium (CM) from LPS-triggered coculture or KC alone decreased protein synthesis of hepatocytes whereas CM from hepatocytes alone had no effect. Gel filtration of active M0-CM showing maximal hepatocyte inhibitory activity was present in fractions between 15,000 and 30,000 daltons. This inhibitory activity was inactivated by exposure to 65 degrees C for 30 minutes. Although CM from untriggered M0 did not inhibit hepatocyte protein synthesis, lysates from both LPS-triggered and control M0 were inhibitory. These results show that M0s/KCs exposed to septic stimuli decrease hepatocyte protein synthesis via heat labile, soluble mediator(s) that may already be synthesized within untriggered cells. We hypothesize that soluble M0/KC mediators normally modulate hepatocyte function and that this normal homeostatic control is profoundly altered during sepsis.

Cell Separation↗
PubMed1986

Paranasal sinusitis associated with nasotracheal intubation: a frequently unrecognized and treatable source of sepsis.

Paranasal sinusitis secondary to prolonged nasotracheal intubation represents an infrequently reported source of sepsis. Of 27 nasally intubated patients who developed paranasal sinusitis over a 1-yr period, 17 patients underwent emergency blind nasotracheal intubation post-trauma or shock (group 1) and the remaining ten were intubated electively under operating room or ICU conditions (group 2). Group 1 patients were younger (mean age 33 +/- 6 vs. 57 +/- 5 yr) than those in group 2; they also developed sinusitis more quickly after intubation (mean time 8 +/- 1 vs. 15 +/- 2 days). Diagnosis was confirmed via sinus x-rays (14 cases), computed tomography (five cases), indium scan (two cases), or clinical picture. Cultures were obtained in 14 cases. Staphylococci predominated in group 1, while nosocomial Gram-negative organisms predominated in group 2. Seven patients developed pulmonary infections and two developed systemic sepsis with an organism present on sinus culture. In all cases treatment was successful with antibiotics and tracheostomy or movement of the tube to the oral route. These data indicate that patients nasally intubated are at risk for development of paranasal sinusitis; this diagnosis should be suspected in sepsis of undetermined etiology.

Adult↗
PubMed1985

Enhanced survival during murine gram-negative bacterial sepsis by use of a murine monoclonal antibody.

We developed a murine monoclonal antibody (5B10 MAb) that reacted in vitro specifically to lipopolysaccharide (LPS) obtained from Escherichia coli 0111:B4. Enzyme-linked immunosorbent assay (ELISA) titers to a variety of gram-negative bacterial whole cell and LPS antigens demonstrated that this antibody may react with the O antigen portion of 0111:B4 LPS. We then examined the ability of this antibody to protect mice in vivo against a challenge of either viable bacteria or purified LPS. One milligram of 5B10 MAb was administered intraperitoneally (IP) and protected against a lethal challenge of either viable E coli 0111:B4 or 0111:B4 LPS, but no other type of bacterial or LPS challenge. Protection occurred in an antibody dose-dependent manner, and as little as 0.01 mg of 5B10 MAb enhanced survival. We concluded that IP pretreatment with a single MAb would protect against lethal sepsis or endotoxemia in this animal model and that anti-LPS specificity was a sufficient condition for an antibody to protect during bacteremia, confirming the importance of LPS in the pathogenesis of gram-negative bacterial sepsis.

Animals↗