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Biomedical subjects

F B Cerra

Publications and source records attributed to F B Cerra.

At least 19 recordsLinked to original sources
PubMed1992

Selective gut decontamination reduces nosocomial infections and length of stay but not mortality or organ failure in surgical intensive care unit patients.

Suppression of the gut luminal aerobic flora to reduce nosocomial infections was tested in a prospective, randomized, double-blind, placebo-controlled clinical trial in patients in a surgical intensive care unit who had persistent hypermetabolism. Forty-six patients were randomized to receive either norfloxacin, 500-mg suspension every 8 hours, together with nystatin, 1 million units every 6 hours, or matching placebo solutions administered through a nasogastric tube within 48 hours of surgical intensive care unit admission. Selective gut decontamination with the experimental therapy or placebo solutions continued for at least 5 days or until the time of surgical intensive care unit discharge. Patients were monitored with routine surveillance cultures for the development of nosocomial infections, as defined by criteria from the Centers for Disease Control. All other therapy was given as clinically indicated, including systemic antibiotics. The selective gut decontamination group experienced a significant reduction in the incidence of nosocomial infections and a reduced length of stay. However, these results were not associated with a concomitant decrease in progressive multiple organ failure syndrome, adult respiratory distress syndrome, or mortality.

Adult↗
PubMed1992

Primary culture of rat hepatocytes entrapped in cylindrical collagen gels: an in vitro system with application to the bioartificial liver. Rat hepatocytes cultured in cylindrical collagen gels.

A static culture model employing cylindrical collagen-hepatocyte gels is reported for large scale testing of conditions relevant to the three compartment hollow fiber bioartificial liver. High density hepatocyte cultivation was achieved by cell entrapment within the collagen-hepatocyte gel. Hepatocyte viability was assessed by vital staining, gel contraction, and insulin utilization. Measures of hepatocyte-specific function included albumin synthesis, ureagenesis, lidocaine biotransformation, and cholate conjugation. Although hepatocyte viability remained stable through the seven day incubation period, hepatocyte functions were not uniformly preserved. Albumin synthesis remained stable, while representative P-450 and conjugation activities decreased with time. This static culture system will facilitate the development of a hollow fiber bioartificial liver which utilizes cylindrical collagen-hepatocyte gels.

Albumins↗
PubMed1992

Thrombolytic therapy for postoperative pulmonary embolism.

The use of thrombolytic agents in the treatment of postoperative pulmonary embolism presents a dilemma to the surgeon. On one hand, postoperative pulmonary embolism usually occurs within 2 weeks of surgery. On the other hand, recent surgery is considered a contraindication for the use of thrombolytics. We developed a protocol for treating pulmonary embolism patients who have recently undergone surgery. Urokinase, at a dose of 2,200 U/kg wt, is injected directly into the clot via a catheter positioned in the pulmonary artery. This is followed by continuous infusions of urokinase at 2,200 U/kg wt/hr until the clot is lysed (up to 24 hrs). Simultaneously, heparin is administered peripherally at 500 U/hr. The level of serum fibrinogen is monitored every 6 hours and maintained at no less than 0.2 g/dL to prevent bleeding. Thirteen patients were treated for angiographically proven pulmonary embolism within 14 days of surgery. Complete lysis of every embolus was achieved, and no deaths or bleeding complications occurred. Two patients received inferior vena cava filters, and nine patients no longer needed chronic anticoagulants within 3 months after the embolic event.

Adult↗
PubMed1992

Multiple organ failure syndrome.

Tissue injury, whether from infection, blood or volume loss, trauma, or inflammation such as pancreatitis, induces local and systemic responses. The systemic responses include shock, reperfusion, systemic inflammation (hypermetabolism) with primary organ dysfunction, and secondary organ dysfunction that either becomes progressive and leads to death or from which the patient recovers and enters into a period of prolonged rehabilitation. Each of these responses has its pathogenesis and treatments that are appropriate and effective. The research indicates that the responses may contribute to the development of cell and organ injury and to progressive multiple organ failure syndrome and death, particularly in the case of the systemic inflammatory response. Current therapy is designed to rapidly remove the cause of injury, resuscitate the microcirculation, and institute nutrition therapy to prevent single and generalized nutrient deficiencies and promote repair and healing. Newer therapies are designed to modulate the inflammatory response itself to minimize its injury potential and promote tissue repair and recovery of the patient. Genetic regulation of metabolism is also a pathogenetic mechanism. Its role in these responses is just starting to be understood--new therapies will need to await this understanding. Once the patient begins to recover, rehabilitation tends to be long and problematic. Nonetheless, significant survival rates are now occurring, with continued improvements expected in response to the newer therapeutic approaches. Planned rehabilitation thus becomes an important component of effective recovery. Professionals trained in critical care and well versed in cellular and molecular biology provide the milieu within which continued improvements in prevention, therapy, and outcome will continue to occur.

Combined Modality Therapy↗
PubMed1992

Hepatocyte function in a hollow fiber bioreactor: a potential bioartificial liver.

We have developed a novel hepatocyte loaded hollow fiber bioreactor as a potential bioartificial liver. Freshly harvested rat hepatocytes were entrapped in a three-dimensional gel matrix within hollow fibers in a perfused bioreactor. Gel entrapment allowed cells to be cultured at high density while maintaining tissue-specific function. Hepatocyte function was evaluated in 10 bioreactors, each containing approximately 5 x 10(7) cells. Oxygen consumption averaged 0.32 pmole/cell/hr, albumin appearance averaged 0.60 pg/cell/hr, and lidocaine clearance (a measure of the P-450 activity) averaged 0.74 pg/cell/hr. Function persisted for the 7 days of the study. Electron microscopy at 7 days showed the distinctive ultrastructure of viable, differentiated hepatocytes: bile canaliculi, intercellular junctions, peroxisomes, abundant mitochondria, and glycogen granules. Maintenance of tissue specific function and ultrastructure suggests that this bioreactor configuration has potential as a device to support patients in liver failure, as well as to study hepatocytes in vitro.

Amino Acids↗
PubMed1992

Role of nutrition in the management of malnutrition and immune dysfunction of trauma.

Current nutrition support improves patient outcome in trauma patients. It appears to do so by limiting the adverse effects of specific nutrient or generalized nutrient deficiencies. Immunosuppression, however, continues as a significant clinical problem. This immunosuppression appears to be part of the inflammatory response that accompanies trauma, and in part, to represent the need for conditional nutrients in this setting. Three nutrients that are being evaluated include arginine, uracil as ribonucleic acid and omega-3 polyunsaturated fatty acids. Animal studies report improved immune function. Early clinical trials are reporting improved immune function and patient outcomes.

Animals↗
PubMed1992

Hepatocyte culture systems for artificial liver support: implications for critical care medicine (bioartificial liver support).

OBJECTIVE: The primary purpose of this review article is to familiarize critical care practitioners with newly developing techniques of hybrid artificial liver support. Implantable and extracorporeal hepatocyte culture systems are emphasized based on their current experimental and clinical status. DATA SOURCES: Data used to prepare this document were obtained from the authors' personal files, as well as the computerized MEDLINE database. Medical headings used include: liver, artificial organs, cell culture, growth hormones, extracellular matrix, and transplantation. Only articles published in English have been cited. STUDY SELECTION: All studies are discussed in which hepatocyte culture systems have been used to support human patients with liver failure. All studies reported the patient's condition before therapy, duration of therapy, and outcome after therapy in order to be included in this review. Since the number of clinical trials is small at this time, animal studies were used to demonstrate application of other systems in the treatment of experimentally induced liver failure. Similar selection criteria were used to select animal studies for review. All initially identified human studies met these selection criteria. DATA EXTRACTION: Independent extraction by multiple observers. DATA SYNTHESIS: Liver failure, resulting from infection, drugs, or as a part of the multiple organ failure syndrome, remains a major cause of morbidity, mortality, and resource allocation. Current therapy is limited to supportive care, along with liver transplantation. Because of these therapeutic limitations, hybrid artificial liver systems have been proposed for temporary and long-term hepatic support. Several animal studies and a small number of preliminary human studies indicate that hepatocyte culture systems are capable of supporting nearly all essential hepatic functions and may supply biologically active substances that promote regeneration and repair of the damaged liver being supported. Hybrid systems may be constructed from materials that serve as immunoprotective barriers against host defenses. CONCLUSIONS: During the past decade, important progress has been made with hybrid artificial liver support systems. Cell culture technology has progressed sufficiently so that an artificial liver, composed of metabolically active hepatocytes, may be a potential reality in the foreseeable future. Both implantable and extracorporeal artificial liver support systems have been developed to provide metabolic support during acute liver failure, or to serve as a bridge to solid organ transplantation. Implantable hepatocyte systems, however, require a prolonged period for intraperitoneal engraftment and vascularization, not typically available to patients with acute liver failure. For this reason, extracorporeal hybrid designs offer the greatest hope for on-line treatment of acute liver failure. Such systems are entering the final stages of animal testing.

Animals↗
PubMed1992

Growth hormone and nutritional support: adverse metabolic effects.

The use of growth hormone in clinical nutritional support has received considerable attention over the past decade. The most encouraging results have been improved nitrogen retention and protein synthesis in the presence of hypocaloric nutritional support. Adverse effects, however, can limit the clinical usefulness of this technology. In the following case study, an obese 71-year-old man with a history of chronic obstructive pulmonary disease remained ventilator dependent 2 months following anterior cervical fusion and had severe depletion of visceral proteins despite nitrogen equilibrium. He was treated with 10 mg of recombinant human growth hormone (Genentech) subcutaneously every other day while also receiving nutritional support. We hypothesized that growth hormone administration could promote both protein synthesis and the development of muscle mass, particularly in the respiratory muscles, without increasing nutrient intake and, therefore, without increasing CO2 production. The patient, however, developed two potentially life-threatening adverse effects: hyperglycemia and fluid retention. The severity of these adverse effects led to discontinuation of this mode of therapy.

Aged↗
PubMed1992

Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine.

An American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference was held in Northbrook in August 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic parameters by which a patient may be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods when dealing with septic patients was recommended as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae.

Critical Care↗
PubMed1992

Sengstaken-Blakemore tube placement. Use of balloon tamponade to control bleeding varices.

The management of acute variceal bleeding continues to challenge those who care for patients with portal hypertension. Survival depends on rapid institution of an established protocol for resuscitation, diagnosis, and management of the patient. Balloon tamponade plays an important part in the management of this problem along with pharmacologic and endoscopic modalities. It is important in closing, however, to note that guidelines for use cannot compensate for lack of experience and the authors agree with Vlavianos and colleagues in stating that without experience in its use, balloon tamponade is of limited value.

Balloon Occlusion↗
PubMed1992

Intestinal bacterial flora, intestinal pathology, and lipopolysaccharide-induced translocation of intestinal bacteria.

The primary aim of this study was to clarify the mechanism and significance of lipopolysaccharide (LPS)-induced translocation of intestinal bacteria. Female Swiss Webster mice were purchased from two different animal suppliers. Twenty-four hours following parenteral LPS, mice from both suppliers had noticeable morbidity and mortality. However, intestinal pathology, gram-negative bacterial overgrowth, and increased bacterial translocation was noted in mice purchased from one supplier but not the other. Mice with increased translocation also had overgrowth of cecal gram-negative bacilli, i.e., 10(10) per gram of cecum following parenteral LPS; in contrast, mice without LPS-induced bacterial translocation had 1,000- to 10,000-fold fewer cecal gram-negative bacilli. Additional groups of mice with increased bacterial translocation were also sacrificed two and 6 hr after parenteral LPS; morbidity and intestinal pathology were evident without a corresponding increase in bacterial translocation. Separate groups of these mice were also injected with platelet activating factor, resulting in intestinal pathology similar to that noted with parenteral LPS, but no increase in bacterial translocation. Thus parenteral LPS was consistently associated with morbidity and mortality but not with intestinal pathology, enteric bacterial overgrowth, or increased bacterial translocation.

Animals↗
PubMed1991

Regulation of murine splenocyte responses by heparan sulfate.

Heparan sulfate is a biologically active glycosaminoglycan found in abundance in endothelium, epithelium, and connective tissues. Although heparan sulfate is an important part of the environment in which immune cells function, its effects on the immune system are largely unknown. When present during the first 24 h of an MLC consisting of MHC disparate murine splenocytes, heparan sulfate had a marked stimulatory effect on the proliferative response to alloantigens. Heparan sulfate also augmented the splenocyte response to suboptimal concentrations of the mitogens Con A, anti-CD3 mAb, and ionomycin. The stimulatory action of heparan sulfate was mediated, at least in part, by increased production of IL-1, because the increased splenocyte proliferation induced by heparan sulfate was substantially inhibited by anti-murine IL-1 alpha-antibodies. In contrast to these stimulatory effects, when heparan sulfate was added to MLC 48 to 72 h after onset, decreased splenocyte proliferation was observed. This inhibitory action was mediated by an increase in PGE2 production; the inhibitory effect could be abrogated with indomethacin. The fact that heparan sulfate is present on cells such as endothelial cells with which T cells interact and is released during activation of endothelial cells (thus making it available in soluble form to cells in the immune response) may allow heparan sulfate to play an important role in modulating cell-mediated immune responses in vivo.

Animals↗
PubMed1991

Nutrient modulation of inflammatory and immune function.

The metabolic response to injury occurs after a diverse group of surgical injuries including major surgical intervention, shock, infection, and sources of inflammation such as pancreatitis. The response is mediated by the macroendocrine system, the autonomic nervous system, and the cell-cell communication system. The clinical manifestations include now well-described clinical, physiologic, and metabolic characteristics. The approach of aggressive source control, invasive circulatory resuscitation, and nutrition/metabolic support has been associated with an overall reduction in morbidity and mortality. In those patients who do not respond to this approach, the disease process progresses to multiple organ failure syndrome with its associated high mortality. Altering the route of feeding, preventing single nutrient and generalized nutrient deficiency, and reducing nosocomial infections with selective gut decontamination have not significantly altered the course or outcome of the disease process in this latter group of patients with persistent hypermetabolism. The available data support the position that this persistent hypermetabolism represents abnormal metabolic regulation resulting in persistence of the inflammatory response with associated suppression of the immune defenses. A number of research approaches are being taken to understand and modulate this abnormal state of regulation. Because of the role of specific nutrients in these regulatory processes, beyond their role in classic nutrition support, nutrients such as arginine n-3 polyunsaturated fatty acids, and RNA are being evaluated for their ability to modulate inflammation and to improve immune function. Preliminary results are encouraging.

Arginine↗
PubMed1991

Increased dietary branched-chain amino acids do not improve growth in developing rats with chronic biliary obstruction.

We studied dietary branched-chain amino acid enrichment in cholestatic weanling rats. Growth was assessed with body weight, muscle weight and nitrogen balance. Systemic metabolic measurements that reflect liver function were evaluated, including plasma ammonia, albumin, amino acids, glucose, triglyceride and branched-chain ketoacids, as well as urinary carnitine excretion. Twenty-two rats underwent bile-duct ligation at 14 d of age. At weaning, 11 rats were fed a control diet and 11 an isoenergetic, isonitrogenous branched-chain amino acid-enriched diet for 3 wk, each with a sham-operated, pair-fed control. Body weights were similar in all four groups. Changes due to bile-duct ligation and not affected by the diet manipulation included lower plasma glucose, nitrogen balance and muscle weight, and higher triglyceride concentration, carnitine excretion and liver weight. Changes due to ligation that were normalized by dietary manipulation included plasma albumin, ammonia and total amino acid concentrations. The ratio of branched-chain to aromatic amino acids was decreased in ligated animals fed both diets; however, branched-chain amino acids were lower in the two groups fed more branched-chain amino acids.

Administration, Oral↗
PubMed1991

Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial.

The hypothesis that optimizing hemodynamics using pulmonary artery (PA) catheter (preoperative 'tune-up') would improve outcome in patients undergoing limb-salvage arterial surgery was tested. Eighty-nine patients were randomized to preoperative tune-up either in the surgical intensive care unit (SICU) (group 1) or the preinduction room (group 2) or to control (group 3). The tune-up consisted of fluid loading, afterload reduction, and/or inotropic support to achieve predetermined endpoints. Patients with a PA catheter had significantly fewer adverse intraoperative events (p less than 0.05), less postoperative cardiac morbidity (p less than 0.05), and less early graft thrombosis (p less than 0.05) than the control group. The overall study mortality rate was 3.4%, with a mortality rate of 9.5% in the control group and 1.5% in the PA catheter groups. There were no differences in ICU length of stay (LOS), hospital LOS, or total hospital costs, although the percentage of cost from complications was higher in group 3 (p greater than 0.05). In this group of patients, preoperative cardiac assessment and optimization is associated with improved outcome.

Aged↗
PubMed1991

Nitrogen oxide levels in patients after trauma and during sepsis.

The mediators responsible for maintenance of the hyperdynamic state and the low systemic vascular resistance (SVR) observed in sepsis have not been elucidated. Nitric oxide (.N = O) is a mediator with numerous functions, including regulation of vascular tone and a role in macrophage-mediated cytostasis and microbiostasis. Thirty-nine critically ill trauma and septic patients were studied to determine the relationship between .N = O production and the hyperdynamic state. high plasma levels of NO2-/NO3- (the stable end products of .N = O) were observed in septic patients (p less than 0.02). Low SVR and high endotoxin levels were associated with high NO2-/NO3- values (p = 0.029, p = 0.002). Changes in .N = O levels may mediate the vasodilation seen in sepsis. Low NO2-/NO3- levels were observed in trauma patients (p less than 0.001) and remained low even in the presence of sepsis (p = 0.001).

Adult↗
PubMed1991

Amino acid alterations and encephalopathy in the sepsis syndrome.

OBJECTIVE: To evaluate the role of amino acid profiles in septic encephalopathy. DESIGN: Retrospective analysis. SETTING: Medical wards and medical ICU of a university hospital. PATIENTS: Patients with infections and normal mental status were compared with patients with septic shock and altered sensorium. INTERVENTIONS: Plasma amino acid levels and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were determined. MEASUREMENTS AND MAIN RESULTS: Patients with septic shock and altered sensorium had higher circulating concentrations of ammonia (425 +/- 55 vs. 127 +/- 7 mmol/L) and the aromatic amino acids phenylalanine (122 +/- 19 vs. 74 +/- 3 mmol/L) and tryptophan (97 +/- 7 vs. 32 +/- 13 mmol/L), and lower levels of the branch-chain amino acid isoleucine (48 +/- 7 vs. 68 +/- 5 mmol/L) than patients with infections and normal sensorium (p less than .05). Aromatic amino acid levels correlated with APACHE II scores (R2 = .4, p less than .001) and mortality. APACHE II scores were higher in the septic shock patients (30 +/- 2 vs. 8 +/- 1, p less than .001), and these patients had a higher mortality rate (71% vs. 12%, p less than .01). Patients with septic shock who died had higher levels of ammonia (524 +/- 58 vs. 227 +/- 40 mmol/L, p less than .05) and sulfur-containing amino acids (172 +/- 31 vs. 61 +/- 7 mmol/L, p less than .05) than patients who survived. CONCLUSIONS: Plasma amino acid profiles appear to be important in septic encephalopathy and the severity of septic disease.

Amino Acids↗