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Biomedical subjects

F B Cerra

Publications and source records attributed to F B Cerra.

At least 37 records · Page 2Linked to original sources
PubMed1995

A managed care model for home infusion therapy.

Home infusion therapy began in response to the medical needs of the patients. In the traditional model, products and services were delivered in the home on a physician's prescription. Limitations related to medical quality management and cost were recognized in this model. Because of these limitations, the changes that continue to occur in health care delivery and the increase in number and acuity of patients requiring non-hospital services, a managed care model was conceived and implemented at the University of Minnesota Medical School and Hospital. This model emphasizes physician-based case management, total quality management, a point of contact medical information system, outcomes assessment and management, and research and education activities designed to evaluate and improve home infusion therapies. The model was implemented through a public-private partnership. This application of managed care to home infusion therapies is described in this communication.

Clinical Protocols↗
PubMed1995

An anesthetized model of lethal canine galactosamine fulminant hepatic failure.

A reproducible large animal model of fulminant hepatic failure was developed in the anesthetized dog by the administration of the amino sugar D-galactosamine. Galactosamine in 5% dextrose in water (D5W), was given as an intravenous bolus to 10 young male dogs weighing 27 to 30 kg. Three dogs that received an equal volume of D5W alone served as controls. Galactosamine at 0.5 g/kg (n = 5) produced significant biochemical evidence of liver injury with 100% survival at 48 hours. Galactosamine 1.0 g/kg (n = 5) yielded in 100% 48-hour mortality resulting from fulminant liver failure characterized by a progressive increase in liver enzymes, total bilirubin, ammonia, and lactate and associated coagulopathy, hypoglycemia, coma, and increased intracranial pressure. Necropsy showed liver pallor, ascites, and brain swelling. Liver histology showed significant hepatocellular necrosis. This clinically relevant large animal model will enable the quantitative evaluation of new technologies, such as the bioartificial liver, for the support of hepatic failure in humans.

Anesthesia↗
PubMed1994

Modulation of cytolytic T cell responses by heparan sulfate.

Accumulating evidence suggests that the functional properties of alloactivated T cells may depend upon the microenvironment in which the T cells reside. For instance, we showed previously that heparan sulfate, a biologically active polysaccharide present on cell surfaces and extracellular matrices, modulates the proliferative responses of splenocytes through enhancement of cytokine and prostaglandin production by macrophages. Here we report that under conditions of suboptimal stimulation, heparan sulfate causes discrete alterations in the functional responses of murine cytolytic T cells. When present in a 5-day mixed leukocyte culture (MLC), heparan sulfate mediates an increase, from 3- to 10-fold, in T cell-mediated cytotoxicity. This increase is dose dependent and most pronounced when heparan sulfate is present in the highest concentration during the first 24 hr of the culture period. On the other hand, when added during the last 48-72 hr of an MLC, heparan sulfate decreases cytotoxicity by 3- to 30-fold. Neutralizing antibodies against IL-1 alpha, but not antibodies against IL1 beta, IL-6, or TNF alpha/beta, abrogate the heparan sulfate-mediated increase in cytotoxicity, suggesting that the increase depended in part upon the production of IL-1 alpha. However, studies in which exogenous IL-1 was added to MLC showed that increased cytotoxicity was not due only to increased cytokine production. Augmentation of cytotoxicity was in part independent of T cell help, as depletion of CD4+ cells from the responder population before MLC, or addition of neutralizing anti-murine IL-2 antibodies plus human IL-2 to the MLC, did not abrogate the stimulatory effect of heparan sulfate. Heparan sulfate-treated CD8+ lymphoblasts isolated after 7 days in MLC demonstrated an increased cytotoxicity, elevated intracellular serine esterase, and perforin levels compared with lymphoblasts from control MLC. The decrease in cytotoxicity observed when heparan sulfate was present during the last several days of an MLC was likely mediated by PGE2, as elevated levels of PGE2 were detected in MLC supernatants of heparan sulfate-treated cultures, and because the decrease was not observed in the presence of indomethacin. Our results are consistent with the idea that the metabolism of heparan sulfate, an endogenous component of parenchymal tissues, may regulate the tempo and magnitude of alloreactive cytotoxic T cell responses.

Animals↗
PubMed1994

Multiple organ failure syndrome in the 1990s. Systemic inflammatory response and organ dysfunction.

OBJECTIVE--This review of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) provides an overview of a common but complex problem found in critically ill patients. It emphasizes definitions, common clinical patterns, metabolic responses, and pathophysiological changes. A brief discussion of treatment concepts is also included. DATA SOURCES--Data for this review were gathered from peer-reviewed journals, review articles by experts in SIRS/MODS, and selections from reference volumes written on SIRS/MODS. STUDY SELECTION--Reference selections were chosen on the basis of quality of research. Peer-reviewed journals were given primary consideration. Those review articles cited were felt to be essential to any discussion of SIRS/MODS. DATA EXTRACTION--Where possible, randomized, controlled, prospective studies were reviewed and conclusions used in this overview of SIRS/MODS. CONCLUSION--Our ability to care for critically ill patients has led to a new problem, SIRS and eventually MODS, which may become progressive organ failure and death. Unfortunately, these conditions are extremely frequent and carry high mortality rates. Increased oxygen consumption demands highlight the physiological response. The typical metabolic responses are characterized by hyperglycemia and accelerated protein catabolism. Unrecognized perfusion deficits, an uncontrolled septic focus, a persistent source of inflammation, or injured tissue is commonly present with SIRS/MODS and should be corrected. Restoration of oxygen transport and metabolic support are also important components of treatment. The cause of SIRS/MODS is complex and not fully understood, but multiple mediators and stimulated macrophages likely are important components and areas where treatment may well be focused.

Critical Illness↗
PubMed1994

Value of routine pressure monitoring system changes after 72 hours of continuous use.

OBJECTIVE: To assess the infection potential of not routinely changing invasive monitoring kits and associated plasticware. DESIGN: A prospective, observational study of microbiological contamination of a cohort of pressure monitoring infusion systems. SETTING: Adult intensive care units in a university tertiary care center. PATIENTS: Patients who had invasively monitored arterial, central venous, or pulmonary artery catheters in place for > or = 96 hrs without a change to the system were entered into the study. INTERVENTIONS: Fluid samples were obtained from the proximal stopcock of the monitoring kits every 24 hrs, beginning with a sample at 72 hrs and continuing until either the plasticware or catheter was changed or discontinued. Fluid samples were placed in tryptic soy broth and spread on blood agar plates within 24 hrs. MEASUREMENTS AND MAIN RESULTS: Of 451 intervals in which the system remained unviolated for > or = 96 hrs except for sampling, no positive cultures were found. Of the 333 monitoring kits/lines in the study, four cultures became positive within 48 hrs of a violation of the system (flush bag change). Positive cultures were obtained from two different patients, one patient having positive fluid cultures from arterial, central venous, and pulmonary arterial kits. This bacterial growth would not have been eliminated with routine system changes as it occurred within a 48-hr timeframe. CONCLUSIONS: Invasive hemodynamic pressure monitoring systems including tubing and plasticware need not be changed routinely as these changes may cause a higher incidence of contamination due to increased violations of the systems.

Adult↗
PubMed1994

Effect of manipulating dietary constituents on the incidence of infection in critically ill patients.

Nutrition status has major implications for the incidence of infectious complications in critically ill patients. Providing macronutrients and micronutrients in appropriate amounts consistent with the metabolism present during the inflammatory response can significantly reduce the incidence of infectious complications. Current data would indicate that the enteral route of nutrition is more effective in this regard when it is used within 3 to 4 days after injury. The composition of the nutrition formulation is also an important factor in influencing the incidence of infectious complications. Avoiding excess calorie administration, administering restricted amounts of omega-6 polyunsaturated fatty acids, and promoting nitrogen equilibrium are all important aspects of nutrition administration that promote the reduction in infectious complications. Despite these effects, infectious complications remain a common problem in critically ill patients. Based on the anti-inflammatory and lymphoproliferative properties of specific nutrients, enteral products have been formulated with increased amounts of these nutrients. The results of current studies with these products indicate a further reduction in infectious complications and length of hospital stay.

Critical Illness↗
PubMed1994

Primary hepatocytes outperform Hep G2 cells as the source of biotransformation functions in a bioartificial liver.

OBJECTIVE: Metabolic activity of transformed human liver (Hep G2) cells and primary rat hepatocytes were compared during in vitro application of a gel entrapment bioartificial liver. BACKGROUND: Clinical trials of bioartificial liver devices containing either transformed liver cells or primary hepatocytes have been initiated. A study comparing transformed liver cells and primary hepatocytes in a bioartificial liver under similar conditions has not been reported previously. METHODS: Gel entrapment bioartificial liver devices were inoculated with 100 million cells, Hep G2 cell line (n = 4), or rat hepatocytes (n = 16), and studied for up to 60 days of in vitro cultivation. RESULTS: Hep G2 cells grew to confluence within the gel entrapment configuration with a doubling time of 20 +/- 3 hours. Rat hepatocytes significantly outperformed Hep G2 cells at confluence in all categories of biotransformation, including ureagenesis (3.5 +/- 0.7 vs. 0.3 +/- 0.1 mumol/hr, p < 0.05), glucuronidation (630 +/- 75 vs. 21 +/- 2 nmol/hr, p < 0.005), sulfation (59 +/- 13 vs. 5 +/- 2 nmol/hr, p < 0.05), and oxidation (233 +/- 38 vs. < 1 nmol/hr, p < 0.005). At the conclusion of one experiment, Hep G2 cells were found in the extracapillary compartment of the bioartificial liver, analogous to the patient's compartment during clinical application. CONCLUSIONS: Primary rat hepatocytes were superior to the Hep G2 cell line as the source of hepatic function in a bioartificial liver and avoided the potential risk of tumor transmigration from the bioartificial liver into the patient's circulation.

Albumins↗
PubMed1993

Pulmonary artery catheterization. Can there be an integrated strategy for guideline development and research promotion?

OBJECTIVES: To review the evidence regarding indications for pulmonary artery catheterization (PAC) in critically ill patients, and to propose a guideline-generating process that would encourage randomized controlled trials of PAC. DATA SOURCES: Computerized and manual search for randomized trials involving PAC as an integral part of the protocol, published as of October 1992. Manual search for guidelines endorsed by specialty societies and/or proposed by expert panels following an explicit group process. DATA SYNTHESIS: Four trials suggest benefit from PAC for pre- or perioperative management of high-risk surgical patients. Two others indicate that PAC for low-risk aortic aneurysm surgery confers no advantages. Use of PAC to guide therapy aimed at improved mixed venous oxygen saturation was beneficial compared with usual care with PAC in two small trials among patients with septic shock and severe trauma. Other PAC indications are either untested or inadequately tested by small trials. Large trials are needed, but trials to date have been impeded by clinicians' uncertainty about PAC and unwillingness to randomize critically ill patients. No published guidelines for PAC have used a formal group process and/or a hierarchical review of evidence to demarcate proven from unproven indications. CONCLUSIONS: We propose a research-promoting expert panel on indications for PAC. Aided by a critical literature review, experts would rate case scenarios on the need for routine PAC with or without a specified intervention strategy. Future trials should test indications where there is either consensus about the uncertainty of need for PAC, or interpanelist disagreement owing to inconclusive evidence. This process could facilitate practice guideline development, utilization management, and large trials of PAC and related interventions.

Cardiac Catheterization↗
PubMed1993

Outcome assessment of home parenteral nutrition in patients with gynecologic malignancies: what have we learned in a decade of experience?

Recent improvements in parenteral nutrition and home care delivery systems have made home parenteral nutrition (HPN) a reality for patients with gynecologic malignancies. The records of 61 patients with gynecologic cancers who received HPN between 1981 and 1990 were retrospectively reviewed for outcome, complications, survival, and quality of life. Indications for HPN included mechanical bowel obstruction, short bowel syndrome, malnutrition during cancer therapy, or complications of cancer therapy. Ninety-two percent of patients had disease present at initiation of HPN. Fifty-six percent of patients had ovarian cancer; the remainder had other gynecologic malignancies. The vast majority of patients had prior surgery, radiotherapy, or chemotherapy before receiving HPN. Sixty-four percent of patients underwent cancer treatment (chemotherapy, surgery, or radiation) during HPN. Median survival for ovarian cancer patients on HPN was 72 days and 52.5 days for nonovarian patients (not statistically significant, P = 0.95). Minimal complications were noted from HPN with 9% of hospitalizations due to HPN. Nutritional parameters initially improved in most patients on HPN but then decreased prior to death. Quality of life parameters improved significantly in patients on HPN as compared to pre-HPN status (P < 0.05). In conclusion, HPN is a viable option in gynecologic cancer patients and offers improved quality of life even during the terminal phase of their illness.

Female↗
PubMed1993

Regulation by heparan sulfate and interleukin 1 alpha of the ontogenic expression of T-cell receptor, CD4, and CD8 in developing thymus.

Increasing expression by T-cell precursors of the T-cell antigen receptor and of the CD4 and CD8 glycoproteins during thymus development enables specific interactions between primitive T cells and thymic epithelial cells, which initiate the development of the T-cell repertoire. Given the importance of GAGs, such as HS, in cell-cell interactions in other organs, we asked whether such molecules might participate in the cellular interactions essential for the development of the thymus. Using an organ culture model in which fetal murine thymuses explanted on gestational day 14 undergo phenotypic maturation from CD3-CD4-CD8- to CD3+CD4+/CD8+, the consequences of inhibiting GAG synthesis with 6-diazo-5-oxo-L-norleucine (DON) were explored. Inhibition of GAG synthesis prevented elaboration of cortical thymocyte-associated HS, IL-1, and de novo expression of the TCR, CD4, and CD8. DON did not alter the expression of TCR or CD4/CD8 by mature thymocytes. Synthesis of IL-1 alpha, TCR, CD4, and CD8 was restored by addition of HS to the cultured organs. These findings support the concept that the ontogenic (but not the constitutive) expression of the TCR and of CD4 and CD8 depends on the synthesis in the thymus of IL-1, and that IL-1 synthesis is in turn regulated by the metabolism of GAGs. Our findings suggest that components of the thymic microenvironment, particularly HS, play a critical role in the maturation of T-cell precursors.

Animals↗
PubMed1993

Use of a modified van der Pol's oscillator to construct ventricular pressure-volume relations.

Ventricular pressure-volume (PV) loops provide information about ventricular function. Methodologic constraints have limited derivation of PV loops to the laboratory. The present study addresses derivation of PV loops from a direct left ventricular pressure measurement and left ventricular volume derived from continuous cardiac output. The measurements were performed in vivo in intact, innervated, normal canine hearts. Data from a total of 5 dogs and 13 different cardiac work states were analyzed. A nonlinear oscillator, a van der Pol's oscillator, described the PV relationships. Comparison of left ventricular stroke work derived from the van der Pol's oscillator model with that obtained from ultrasound transducers sutured directly to the myocardium demonstrated a linear correlation, close to the identity line, with R2 = 0.90. Modelling of LV PV loops by this technique was similar to loops derived by experimental measurements. This technique could lead to increased clinical uses for PV relationships.

Animals↗
PubMed1993

Evolution of the bioartificial liver: the need for randomized clinical trials.

The pursuit of a bioartificial liver is well documented in the literature. Early techniques of artificial liver support that have undergone clinical testing included simple exchange transfusions, extracorporeal xenogeneic or allogeneic liver perfusion, cross-circulation, hemodialysis, charcoal hemoperfusion, and plasmapheresis with plasma exchange. These techniques failed because they were unable to adequately support those hepatic functions essential for survival and because they lacked a back-up therapy, such as liver transplantation, for irreversible forms of liver disease. The concept evolved that hepatic functions essential for survival would be best performed by hepatocytes in an apparatus that allowed sustained or repetitive application. The best results have been achieved with bioartificial liver technologies that employ hepatocytes as implantable systems or extracorporeal devices. Implantable bioartificial liver systems include hepatocytes that have been on coated microcarrier beads, within microencapsulated gel droplets, within biodegradable polymeric substrates, or as spheroid hepatocyte aggregates. Extracorporeal systems include hepatocytes in suspension, on flat plates, and in hollow fiber bioreactors. Several extracorporeal systems have undergone extensive animal testing and are entering the early stages of human clinical trials. Randomized trials are needed to establish the value of bioartificial liver support in the treatment of patients with acute hepatic failure or as a bridge to liver transplantation.

Animals↗
PubMed1993

Hemodynamic, respiratory, and metabolic effects of laparoscopic cholecystectomy.

In 10 patients undergoing laparoscopic cholecystectomy, creation of pneumoperitoneum caused immediate venous hypertension and stasis in the lower extremities as measured by percutaneous catheter and duplex scanning. These changes disappeared after deflation. As measured by spirometry, significant reductions in forced vital capacity of 23% and forced expiratory volume in 1 second of 22% were present 24 hours after surgery, and plasma interleukin-6 levels rose to 18 pg/mL. The visual analogue scale of resting pain increased to a median value of 2.5 postoperatively. When compared with other studies of open cholecystectomy, our results showed fewer restrictions of ventilation, lower cytokine levels, and lower pain scores. The minimal soft tissue trauma and early ambulation after laparoscopic cholecystectomy may decrease the risk of thrombosis despite an acute episode of venous stasis.

Blood Flow Velocity↗
PubMed1993

Physiologic response of stress and aminoglycoside clearance in critically ill patients.

OBJECTIVE: To examine the relationships between aminoglycoside clearance and physiologic parameters associated with the physiologic response to injury. DESIGN: Cross-sectional study of surgical patients receiving aminoglycoside pharmacokinetic monitoring and parenteral nutritional support. SETTING: An adult surgical ICU. PATIENTS: Fifty-four surgical/trauma patients who had Gram-negative sepsis. INTERVENTIONS: Measurements of the physiologic stress response to injury were associated with aminoglycoside clearance in 54 surgical/trauma patients who had Gram-negative sepsis. Measurements used to estimate the magnitude of the stress response included a 24-hr urinary urea nitrogen excretion, blood urea nitrogen, peak temperature, serum albumin, bilirubin, and transferrin concentrations. MEASUREMENTS AND MAIN RESULTS: Mean drug clearance rate (4.4 +/- 2.5 [SD] L/hr) was related to the physiologic measurements using correlation and regression techniques. Collectively, all physiologic indices (utilized) explained 59% of the variance in drug clearance (p < .001), an amount similar to the variance explained by creatinine clearance alone (53%). When all six physiologic measurements were included into a multiple regression model that included creatinine clearance, the total variance explained increased to 73%. CONCLUSIONS: Along with renal function estimates, the physiologic response to stress should be considered when treating critically ill patients with aminoglycosides and other, similar, renally eliminated drugs.

Adolescent↗
PubMed1993

Early enteral feeding does not attenuate metabolic response after blunt trauma.

Enteral feeding very early after trauma has been hypothesized to attenuate the stress response and to improve patient outcome. We tested this hypothesis in a prospective, randomized clinical trial in patients with blunt trauma. Following resuscitation and control of bleeding, 52 patients were randomized to receive early feedings (target, < 24 hours) or late feedings (target, 72 hours). Feeding was given via nasoduodenal feeding tubes. A rapid advance technique was used to achieve full volume and strength within 24 hours (goal, 1.5 g protein/kg.day). Patients who underwent at least 5 days of therapy were considered to have completed the study: 38 in all, 19 in each feeding group. Patients were similar in age, gender, Injury Severity Score, and mean PaO2/FiO2 ratio. The early group, however, had more patients with a PaO2/FiO2 < 150. After feeding began, the amount fed per day was the same in both groups. We found no significant differences in metabolic responses as measured by plasma lactate and urinary total nitrogen, catecholamines, and cortisol. Both groups achieved nitrogen retention. In addition, we found no significant differences in intensive care unit (ICU) days, ventilator days, organ system failure, specific types of infections, or mortality, although the early group had a greater number of total infections. In this study, early enteral feeding after blunt trauma neither attenuated the stress response nor altered patient outcome.

Adult↗
PubMed1993

Staining with fluorescein diacetate correlates with hepatocyte function.

To establish the importance of fluorescein diacetate (FDA) as a viability stain for cultured hepatocytes, we hypothesized that FDA staining would correlate positively with hepatocyte viability and function. Mixtures of live and dead cells were stained with FDA and scanned by flow cytometry. A close correlation was observed between the live cell fraction and percent viability as determined by FDA staining (R2 = 0.962). Hepatocytes were also sorted into low fluorescence and high fluorescence groups. Both albumin production and lidocaine metabolism (P-450 activity) were significantly increased in the high fluorescence group compared to the low fluorescence group. An automated, fluorescence-activated assay was useful for rapid assessment of hepatocyte viability. In addition, the intensity of green fluorescence following staining with FDA correlated well with two specific measures of hepatocyte function.

Albumins↗