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Biomedical subjects

F Cerra

Publications and source records attributed to F Cerra.

At least 19 recordsLinked to original sources
PubMed2000

Pulmonary artery catheterization and clinical outcomes: National Heart, Lung, and Blood Institute and Food and Drug Administration Workshop Report. Consensus Statement.

OBJECTIVE: The efficacy and safety of the pulmonary artery catheter are under scrutiny because of its association with increased morbidity and mortality in observational studies. In response, the National Heart, Lung, and Blood Institute (NHLBI) and the US Food and Drug Administration (FDA) conducted the Pulmonary Artery Catheterization and Clinical Outcomes workshop in Alexandria, Va, on August 25 and 26, 1997, to develop recommendations regarding actions to improve pulmonary artery catheter utility and safety. PARTICIPANTS: The NHLBI and FDA planning task force selected a workshop chairperson, subcommittee chairs, and participants. Approximately 85 participants were selected for their collective expertise in critical care, pulmonary medicine, cardiovascular medicine and surgery, pediatrics, nursing, biostatistics, and medical economics. The meeting was open to industry representatives and other government and lay observers. This workshop was funded by the NHLBI and the FDA's Division of Devices. EVIDENCE: Published reports relating to the efficacy and safety of the pulmonary artery catheter, especially consensus documents developed by professional societies. CONSENSUS PROCESS: The planning task force disseminated materials, held teleconferences, and developed draft position papers prior to the workshop. These were modified during the workshop and thereafter in the course of several teleconferences, and presented to the entire group for final modifications and approval. CONCLUSIONS: A need exists for collaborative education of physicians and nurses in performing, obtaining, and interpreting information from the use of pulmonary artery catheters. This effort should be led by professional societies, in collaboration with federal agencies, with the purpose of developing and disseminating standardized educational programs. Areas given high priority for clinical trials were pulmonary artery catheter use in persistent/refractory congestive heart failure, acute respiratory distress syndrome, severe sepsis and septic shock, and low-risk coronary artery bypass graft surgery. JAMA. 2000;283:2568-2572

Catheterization, Swan-Ganz↗
PubMed1994

Blunt injury augments interleukin-6 but not tumor necrosis factor in isolated, perfused rat hindlimbs.

An isolated, perfused hindlimb model in rats was used to examine the immediate inflammatory response after blunt tissue injury. A femur-fracture degloving model was used in isolated rat hindlimbs perfused with a modified Kreb's buffer (pH 7.4) containing albumin, washed human red blood cells (RBCs), amino acids, and glucose at 37 degrees C. Arterial and venous perfusate was sampled at 5, 20, and 80 minutes of perfusion. Initial experiments were conducted in perfusate void of white blood cells (WBCs), group 1 (-inj/-WBC, n = 6) and group 2 (+inj/-WBC). Subsequent experiments were conducted in perfusate containing activated WBCs, group 3 (-inj/+WBC, n = 6) and group 4 (+inj/+WBC, n = 7). Hindlimb muscle was analyzed for adenylate energy charge (EC) and lactate-to-pyruvate ratios (LPR) at the end of each perfusion. This preparation appeared metabolically stable in that oxygen consumption and lactate remained stable during the 80-minute perfusion and muscle EC and LPR indicated aerobic metabolism. Tumor necrosis factor (TNF) and thromboxane B2 (TXB2) were measured in all four groups while prostaglandin F (PGF1 alpha), IL-6, myeloperoxidase, and 8-isoprostane were measured in groups 3 and 4. Initial perfusions in the -WBC hindlimbs indicated no change in TNF release after injury. The TXB2 level increased during perfusion irrespective of injury. The PGF1 alpha was elevated at 80 minutes in both groups 3 and 4, however at 20 minutes PGF1 alpha levels were higher in group 4 compared with group 3. Interestingly, the IL-6 level was significantly elevated at 80 minutes in group 4 but not in group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Descriptive analysis of critical care units in the United States: patient characteristics and intensive care unit utilization.

OBJECTIVE: To gather data about occupancy, admission characteristics, patients' ages, and types of therapy utilized in ICUs in the United States. DESIGN AND SETTING: Survey instruments were mailed to the administrators of 4,233 hospitals to gather information from the medical director of the institutions' respective ICUs for the purpose of developing a database on ICUs in the United States. The sampling frame for this study was based on all American Hospital Association (AHA) hospitals stating they had ICUs. MEASUREMENTS: Census questionnaires solicited information on occupancy, where the patients were admitted from, length of stay, therapies rendered, intensive care diagnoses, and resuscitation status, as well as other information. MAIN RESULTS: Data were obtained regarding 32,850 ICU beds, with 25,871 patients from 2,876 separate ICUs in 1,706 hospitals in the United States. The census response rate was 40% of the AHA hospitals that stated they had ICUs, with specific ICU data on 38.7% of the nation's ICUs. Overall, the responding units reported a mean occupancy rate of 84% of total bed capacity and 87% of available beds. As hospital size increased, so did ICU occupancy. Nearly 17% of all of the critical care patients had been in the units for > 14 days. More precisely, 49% of all responding units indicated that they had one or more "chronic" (> 14-day length of stay) patients. Most patients were admitted to the units from the emergency room (38%), operating room/postanesthesia care unit (22%), and the general hospital floor (16%). Neonatal units were exceptions to this observation, where most patients came from the delivery room (60%). Admission from other hospitals represented a significantly larger group of patients in the cardiac care, pediatric, and neonatal units. Respondents indicated that many of their current patients were elderly, with 43% of these patients aged 65 to 84 yrs and with 4% being > or = 85 yrs of age. The 47% of patients > or = 65 yrs of age increased to 58% when the neonatal and pediatric units were eliminated from the analyses. For all units responding to the survey, the leading primary admitting intensive care diagnoses were postoperative management, ischemic heart disorder, respiratory insufficiency/failure, and prematurity. Elimination of units predominantly treating children (pediatric and neonatal) from the analysis left "adult" units with three primary admitting diagnoses: ischemic heart disease, postoperative management, and respiratory insufficiency/failure with variation according to specific unit type. The leading diagnoses in pediatric units were respiratory insufficiency/failure, postoperative management, and congenital abnormalities. For neonatal units, prematurity was the primary admitting diagnosis, accounting for 59% of these units' patients. Respondents reported 5.3 +/- 10.9% of patients had received cardiopulmonary resuscitation (CPR) before admission into the critical care unit. Only 6.0 +/- 11.9% of patients in these critical care units had instructions that CPR not be performed while in the unit. CONCLUSIONS: This report should be viewed as the beginning step of an effort to improve both the information base available on critical care medicine and the performance of ICUs. Our survey findings provide an introduction into the everyday workings of critical care units throughout the United States. Research is required to determine which patients will benefit from intensive care and how to efficiently utilize the vast technology we have available for them in a world with limited financial resources, an aging population, and a multiplicity of societal and ethical concerns.

Adolescent↗
PubMed1992

Hemicorporectomy for acute aortic occlusion: a case study.

Hemicorporectomy has been done for potentially curable pelvic malignancy and for intractable pelvic sepsis with bone involvement. In this report, the authors describe the first use of hemicorporectomy to treat ischemic gangrene of the limbs and pelvic soft tissues secondary to acute aortic occlusion.

Acute Disease↗
PubMed1990

Tumor necrosis factor production by Kupffer cells requires protein kinase C activation.

Tumor necrosis factor (TNF) has been proposed as a primary inflammatory mediator of septic shock. In vitro and in vivo studies indicate that endotoxin- or lipopolysaccharide (LPS)-activated macrophages are a principle source of TNF; however, membrane signal transduction and intracellular pathways by which LPS triggers TNF production in macrophages are unclear. Recent evidence indicates that specific protein phosphorylation via activation of protein kinase C (PKC) is an early, critical step in the signaling of macrophage TNF production by phorbol esters. We hypothesize that PKC activation is also required in LPS-signaled Kupffer cell (KC) TNF production. Murine KCs were obtained by liver perfusion and digestion and then stimulated with LPS (Escherichia coli O111:B4) or LPS in the presence of H-7, a selective PKC inhibitor. Conditioned media was collected at 3 hr for assay of TNF utilizing the L929 cytolysis bioassay standardized to murine-rTNF-alpha. We found that H-7 inhibited significantly LPS signaled TNF release at a concentration of 10 microM, while H-8 (a cyclic nucleotide specific inhibitor) had no effect. The effect of H-7 was dose dependent and present at varying concentrations of LPS. Down regulation of PKC activity by preincubation of KCs with phorbol myristate acetate (PMA, a direct activator of PKC) also resulted in significantly reduced TNF release after LPS stimulation. The inhibitor H-7 (10 microM) also significantly inhibited LPS signaled prostaglandin E2 release in Kupffer cells. Total and specific intracellular protein phosphorylation was determined by trichloroacetic acid precipitation and SDS-polyacrylamide gel electrophoresis after labeling stimulated Kupffer cells with 32Pi. Total protein phosphorylation was not significantly altered by LPS stimulation; however, autoradiograms from PMA- and LPS-stimulated KCs demonstrate enhanced phosphorylation of a 40-kDa protein (2.7 +/- 0.9-fold) and a 33-kDa protein (3.1 +/- 1.0-fold) which were inhibited by H-7. We conclude that activation of PKC and protein phosphorylation are required steps in the signal transduction pathway of LPS-stimulated TNF production in Kupffer cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Amputation prevention in an independently reviewed at-risk diabetic population using a comprehensive wound care protocol.

An independent review panel composed of an orthopedic surgeon, a vascular surgeon, and an endocrinologist was convened to conduct a case history review. The 71 patients reviewed had 124 wounds on 81 limbs and participated in the comprehensive wound management program of the University of Minnesota. Based on their expertise, the review panel classified the wounds by severity and identified the limb's risk for amputation. The resulting scores were then compared with the patient's actual outcome. The review panel predicted 65 (80%) of the limbs would be salvaged and 16 (20%) would be amputated. The actual outcome was that 75 (93%) of the limbs were salvaged and 6 (7%) were amputated (p less than 0.005). The university's wound management program was highly successful, compared with the predictions of the reviewers.

Amputation, Surgical↗
PubMed1990

Catheter-related sepsis: prospective, randomized study of three methods of long-term catheter maintenance.

We studied the infectious risk of different methods of managing vascular catheters during long-term use. Consecutive surgical ICU patients requiring triple lumen catheters, pulmonary artery catheters, or arterial catheters for greater than 7 days were prospectively randomized to one of three management groups: a) percutaneous (PERC) puncture with every 7-day catheter change at a new site, b) no weekly change (NWC) with a new site when changed, or c) guidewire exchange (GWX) with every 7-day catheter change at the same site. In all groups, a catheter change was mandatory for a positive blood culture, skin site infection, or sepsis without a likely source. Cultures were obtained when clinically indicated and at the time of every catheter change. Catheter-related sepsis (CRS) was defined as a positive blood culture and catheter culture with the same organism. A total of 112 patients met evaluation criteria. There were no intergroup differences in age, primary diagnosis, severity of injury or illness, number of study days, number of protocol violations, route of catheterization, number of catheters present/patient day, catheter sepsis rate, or bacteremia rate. The NWC group demonstrated an increased number of days/catheter, fewer catheter/subcutaneous tract segment cultures/patient, and a reduced incidence of catheter tip colonization. These results occurred in a setting where the number of CRS episodes/patient was 0.17 for GWX, 0.22 for PERC, and 0.16 for NWC. We conclude that there is no difference in infectious risk between these three methods of long-term catheter management. The method with the least complications and expense should be used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Stimulation of repair in chronic, nonhealing, cutaneous ulcers using platelet-derived wound healing formula.

Chronic, nonhealing, cutaneous ulcers are a serious clinical problem. The results of previous studies using platelet-derived wound healing formula (PDWHF), derived from autologous platelets, provided evidence that PDWHF actively stimulates repair of the wound. To test whether or not PDWHF accelerates repair, a prospectively randomized, blinded trial was conducted using a placebo control. A total of 32 patients with chronic, nonhealing, cutaneous wounds of the lower extremity were randomized and treated for eight weeks with PDWHF or placebo. Epithelialization of the wound was the end point of study. In the group who received treatment, 81 per cent of patients had epithelialization in eight weeks compared with 15 per cent in the control group (p less than 0.0001). After crossover to treatment with PDWHF, all of the patients in the control group had epithelialization in an average of 7.1 weeks. Regression analysis of the rates of epithelialization also showed significant differences during the initial eight week trial and showed no difference after crossover of the control group to therapy with PDWHF. Results from this study demonstrate a highly statistically significant effect of topically applied platelet-derived growth factors on the repair of chronic, nonhealing, cutaneous ulcers.

Chronic Disease↗
PubMed1989

Hypoxia and endotoxin induce macrophage-mediated suppression of fibroblast proliferation.

Cellular mechanisms and environmental factors contributing to wound failure following shock and wound contamination are unclear. The activation of macrophages by exposure to hypoxia (pO2 less than 20) and/or lipopolysaccharide (10 micrograms/ml) in vitro was investigated for its effect on macrophage regulation of fibroblast proliferation. The effect on fibroblast proliferation of conditioned medium from activated murine macrophages or co-culture with activated macrophages was tested by measuring 3T3 fibroblast incorporation of 3H-thymidine and culture DNA content. Unstimulated macrophages produced growth factors that increase fibroblast proliferation (proliferation index (PI) = 1.4 +/- 0.15, p less than 0.05 vs. control). Activation by hypoxia alone had little effect on macrophage regulation of fibroplasia (PI = 1.55 +/- 0.28, N.S. vs. unstimulated macrophages). LPS activated macrophages suppressed fibroplasia and the combination of hypoxia with LPS augmented the suppression (PI = 0.5 +/- 0.11, LPS alone, p less than 0.05 and 0.25 +/- 0.05, LPS + hypoxia, p less than 0.01). In addition, hypoxia + LPS treated co-cultures had reduced DNA contents, suggesting reduced cell numbers (12.5 +/- 2.6 micrograms vs. 8.2 +/- 2.0 micrograms). We screened several macrophage cytokines for their direct effect on 3T3 proliferation and found that mr-Tumor Necrosis Factor-alpha (150 units) also suppressed proliferation. Conditioned supernatants from LPS activated macrophages contained 12 +/- 2 units of mrTNF as measured by L929 cytolysis; however, this was significantly less than required to induce suppression of proliferation by direct addition. The regulatory role of the macrophage appears to be dependent on its level of activation. Activation by hypoxia and LPS altered macrophage regulation of fibroblast proliferation from stimulation to suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Nutritional support in acute pancreatitis.

Acute pancreatitis often results in a hyperdynamic, consumptive state. Hallmarks of this condition are decreased peripheral resistance with increased cardiac output. Hemodynamic and cardiovascular changes are accompanied by metabolic alterations. Increased protein catabolism, increased ureagenesis, glucose intolerance, increased lipolysis, and reduced servoregulation are metabolic changes commonly seen in this syndrome. To preserve organ structure and function, biochemical processes must be metabolically supported. Substrate needs change as stress level increases. The per cent of total calories provided as protein must increase. Branched-chain-enriched amino acid solutions have been shown to improve nitrogen utilization in hypermetabolic patients and may therefore be beneficial for the patient with acute pancreatitis. Glucose utilization decreases and free fatty oxidation increases. A mixed fuel system that provides fat, protein, and glucose is suggested for these patients. IV fat has been shown to be a safe energy substrate for patients with pancreatitis in the absence of hyperlipidemia. Failure to use fat as an energy substrate in conjunction with TPN may result in hepatic steatosis and excess carbon dioxide production. The decision of whether to use the parenteral or enteral route to nutritionally support the patient with pancreatitis remains controversial. TPN may allow maintenance of pancreatic rest. The role of enteral feedings is less clear. However, it has been shown that the further down the alimentary tract the feeding is infused, the less pancreatic stimulation occurs. Therefore, it seems wise to support the patient with TPN during severe acute pancreatitis. Jejunal enteral feedings should be initiated as a transitional feeding when the acute inflammatory episode begins to subside.

Acute Disease↗
PubMed1988

Natural killer cell activity: age, estrous- and circadian-stage dependence and inverse correlation with metastatic potential.

The timing within the estrous cycle of surgical removal of a transplanted murine mammary tumor profoundly influences the frequency of pulmonary metastases. We investigated the potential role of the immune response in this phenomenon by measuring splenic natural killer (NK) cell activity and interleukin-2 (IL-2) production in syngeneic tumor-free mice of two age groups at each of two circadian times and in each of four estrous stages. Estrous stage was determined by assessment of vaginal smear cellularity immediately prior to killing and spleen harvest. In a single-cell splenocyte preparation, NK cytotoxicity against a standard tumor cell target was assessed using a radiolabeled chromium release assay while IL-2 activity was determined in a bioassay utilizing the IL-2-dependent CTLL-2 cell line. Mice from the younger group were found to have eight-fold higher NK activity and 35% greater IL-2 production. After normalization of NK and IL-2 values for age, a highly statistically significant difference in NK activity was found among the four estrous and between the two circadian stages of sacrifice. NK activity was greater during the daily resting span across every estrous stage. IL-2 values were highest in diestrus and proestrus when sampled in the light span and in estrus-metestrus when sampled in the dark. The stages within the fertility cycle associated with lowest metastatic potential (proestrus/estrus) correspond precisely with those of highest splenocyte NK activity. These results indicate that an important component of the cellular immune response varies rhythmically both during the fertility and circadian cycles of the host. The rhythmic changes in NK activity may be in part responsible for the similarly rhythmic frequency of postsurgical metastatic dissemination.

Age Factors↗
PubMed1987

The effect of stress level, amino acid formula, and nitrogen dose on nitrogen retention in traumatic and septic stress.

Eighty-seven patients were entered into a randomized, prospective, double-blind, six-center study to evaluate the effect of amino acid loading and a formula that was branched chain enriched (50%) on nitrogen retention in metabolic stress. The patients had varying levels of metabolic stress (0-3) after major surgery, polytrauma, or surgical sepsis. The study was isocaloric and isonitrogenous and lasted for 7 days. The patients received either a standard amino acid formula (SAA) (Travasol) or a 50% branched chain enriched formula that was equimolar, leucine, isoleucine, and valine (MAA) (Travasol + Branchamin concentrate) at a dose of 1.0-2.0 g/kg/day in a fixed ratio with 114 glucose calories per gram of nitrogen administered. The nitrogen retention was proportionate to the nitrogen (and, therefore, caloric) load in both groups. The MAA group, however, had better nitrogen retention, reached nitrogen equilibrium at a lower dose of amino acids, and had less urinary nitrogen excretion per gram of nitrogen administered. Since the groups were isonitrogenous and the calorie to nitrogen ratios were fixed, it appears that nitrogen equilibrium in surgical stress is proportionate to the amino acid load over a range of 0.05-0.4 g/kg/day of nitrogen; and that MAA are more efficient at inducing nitrogen retention and a reduction in urea excretion. These effects on nitrogen retention were more significant at level 2 stress or greater. At these higher stress levels, a dose of 2 +/- 0.2 g/kg/day of MAA seemed most efficient in promoting nitrogen retention.

Adult↗
PubMed1987

Plasma amino acid clearance as an indicator of hepatic function and high-energy phosphate in hepatic ischemia.

A major function of the liver is to maintain normal levels of plasma amino acids. This function may depend in part on tissue levels of high-energy phosphate. Experiments were performed in adult mongrel dogs to assess the relationship between plasma amino acid clearance (PAAC) and tissue high-energy phosphate after 90 minutes of warm hepatic ischemia. In addition, when PAAC was assessed in the anhepatic dog, PAAC fell to low levels after hepatectomy. After 90 minutes of warm ischemia, both tissue adenosine triphosphate (ATP) and PAAC fell to low levels, with PAAC similar to those levels observed in anhepatic dogs. Recovery of ATP and PAAC progressed over a 48-hour period but did not reach control values. Mortality rate was 33% in a group of 12 animals at 48 hours after ischemia. At 24 hours after ischemia, total free plasma amino acid levels were significantly higher in those animals that were dying as compared with those that were surviving (4352 mumol/L versus 2850 mumol/L; p less than 0.05). There was a strong correlation between PAAC and ATP (r = 0.81). PAAC appears to be an indicator of hepatic functional recovery and tissue ATP levels after ischemia.

Adenine Nucleotides↗
PubMed1982

Alpha1-acid glycoprotein concentration and protein binding in trauma.

Alpha 1-Acid glycoprotein (AAG) concentrations were measured every 2 to 3 days in eight trauma patients and seven healthy subjects for approximately 3 wk. Mean AAG concentrations in the trauma patients rose from 100 mg/dl to a peak value of 243 mg/dl at 10 to 14 days. AAG levels averaged more than 200 mg/dl at 15 to 21 days. Mean AAG concentration in healthy subjects was 70 mg/dl with little inter- or intraindividual variability. Lidocaine was added to all serum samples from four of the patients and to selected samples from all of the healthy subjects and protein binding was determined. The binding ratio (bound concentration/free concentration) correlated strongly with AAG concentration in the trauma patients (r = 0.92), in the healthy subjects (r = 0.84), and in both groups combined (r = 0.96). AAG concentration and binding ratio for each of the four patients individually also correlated (P less than 0.05 in all cases). The change in free fraction associated with this increase in AAG was approximately doubled in each patient. Similar findings with drugs commonly used in trauma patients would be expected to alter serum concentration-response relationships significantly.

Adolescent↗
PubMed1981

Multiple systems organ failure: VII. Reduction in plasma branched-chain amino acids--correlations with liver failure and amino acid infusion.

Lower fractional concentrations of branched-chain amino acids were found in trauma-septic patients who did not survive than in those who survived (p values less than or equal to 0.046 to 0.001). A liver dysfunction scale was constructed on the basis of the levels of plasma bilirubin, albumin, SGOT, prothrombin time, and neurologic encephalopathy. Increased liver dysfunction was associated with reduced plasma fractional branched-chain amino acids for all branched-chain amino acids in both the surviving and nonsurviving patients except for valine in the nonsurviving group. This decrease was statistically significant (p less than or equal to 0.041 to 0.001) for leucine and isoleucine in the nonsurvivors and for valine in the survivors. The infusion of amino acids was associated with a decrease in the fractional concentrations in the nonsurvivors for leucine while the fractional concentrations of isoleucine in the nonsurvivors and isoleucine and valine in the survivors rose. The statistically significant changes (p less than 0.018 to 0.001) were for leucine in the nonsurvivors and isoleucine and valine in the survivors. When the liver dysfunction and amino acid infusion related changes are taken in;to account there were no significant differences in the fractional branched-chain concentrations between survivors and nonsurvivors. Liver dysfunction and low fractional branched-chain amino acids were linked in magnitude in a way that is consistent with the low branched-chain amino acids producing the liver dysfunction.

Amino Acids↗