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499 records · Page 28Linked to original sources
PubMed2004

Selective mass treatment with ivermectin to control intestinal helminthiases and parasitic skin diseases in a severely affected population.

OBJECTIVE: To assess the short-term and long-term impact of selective mass treatment with ivermectin on the prevalence of intestinal helminthiases and parasitic skin diseases in an economically depressed community in north-east Brazil. METHODS: An intervention was carried out in a traditional fishing village in north-east Brazil where the population of 605 is heavily affected by ectoparasites and enteroparasites. The prevalence of intestinal helminths was determined by serial stool examination and the prevalence of parasitic skin diseases by clinical inspection. A total of 525 people out of a target population of 576 were treated at baseline. The majority of these were treated with ivermectin (200 microg/kg with a second dose given after 10 days). If ivermectin was contraindicated, participants were treated with albendazole or mebendazole for intestinal helminths or with topical deltamethrin for ectoparasites. Follow-up examinations were performed at 1 month and 9 months after treatment. FINDINGS: Prevalence rates of intestinal helminthiases before treatment and at 1 month and 9 months after mass treatment were: hookworm disease 28.5%, 16.4% and 7.7%; ascariasis 17.1%, 0.4% and 7.2%; trichuriasis 16.5%, 3.4% and 9.4%; strongyloidiasis 11.0%, 0.6% and 0.7%; and hymenolepiasis 0.6%; 0.4% and 0.5%, respectively. Prevalence rates of parasitic skin diseases before treatment and 1 month and 9 months after mass treatment were: active pediculosis 16.1%, 1.0% and 10.3%; scabies 3.8%, 1.0% and 1.5%; cutaneous larva migrans 0.7%, 0% and 0%; tungiasis 51.3%, 52.1% and 31.2%, respectively. Adverse events occurred in 9.4% of treatments. They were all of mild to moderate severity and were transient. CONCLUSION: Mass treatment with ivermectin was an effective and safe means of reducing the prevalence of most of the parasitic diseases prevalent in a poor community in north-east Brazil. The effects of treatment lasted for a prolonged period of time.

Adult↗
PubMed1996

Influence of different volume therapies and pentoxifylline infusion on circulating soluble adhesion molecules in critically ill patients.

OBJECTIVE: To study the influence of long-term volume therapy with different solutions and continuous administration of pentoxifylline on plasma concentrations of circulating adhesion molecules. DESIGN: Prospective, randomized study. SETTING: A surgical intensive care unit (ICU) of a university hospital. PATIENTS: Forty-two patients with sepsis secondary to major surgery were included. INTERVENTIONS: The patients were randomly separated into three groups. In group 1 (n=14), volume therapy was exclusively carried out with 10% low-molecular-weight hydroxyethyl starch solution. In group 2 (n=14), patients exclusively received 20% human albumin for volume therapy. In group 3 (n=14), volume therapy was not defined and pentoxifylline was continuously given (1.4 mg/kg/hr iv). MEASUREMENTS AND MAIN RESULTS: From arterial blood samples, plasma concentrations of soluble adhesion molecules (endothelial leukocyte adhesion molecule-1 [soluble ELAM-1], intercellular adhesion molecule-1 [soluble ICAM-1], vascular cell adhesion molecule-1 [soluble VCAM-1], and soluble granule membrane protein-140) were serially measured on the day of admission to the ICU ("baseline" value) and during the next 5 days at noon. No significant differences between the three groups were found for macrohemodynamics. Soluble ELAM-1, soluble ICAM-1 and soluble VCAM-1 plasma concentrations were markedly higher than normal values at baseline in all groups. In the hydroxyethyl starch group, soluble ELAM-1 plasma concentration decreased to the normal range, whereas it further increased in the human albumin group and was almost unchanged in the pentoxifylline group. During the study period, soluble ICAM-1 and soluble VCAM-1 plasma concentrations remained unchanged in the hydroxyethyl starch group. However, these concentrations increased in the other groups. Soluble granule membrane protein-140 increased significantly only in the human albumin group (483 +/- 103 to 683 +/- 94 ng/mL). In the hydroxyethal starch-treated patients, Acute Physiology and Chronic Health Evaluation II score decreased significantly (from 24.3 +/- 3.4 at baseline to 17.0 +/- 3.3 at the end the study period). Only PaO2/FIO2 was correlated to plasma concentrations of adhesion molecules. CONCLUSIONS: Sepsis is associated with markedly increased plasma concentrations of adhesion molecules, indicating endothelial activation or damage. By long-term volume therapy with hydroxyethal starch solution, these concentrations remained unchanged or even decreased, whereas in patients in whom human albumin was infused or pentoxifylline was given continuously, plasma concentration of soluble adhesion molecules further increased.

Aged↗
PubMed2005

Identification of brain-derived neurotrophic factor as a novel functional protein in hepatocellular carcinoma.

This study aims to identify a novel molecule that may contribute to hepatocarcinogenesis in a rat orthotopic hepatocellular carcinoma model. The hepatocellular carcinoma model was generated by injection of tumor cells into the left lobe of the liver. Proteomic approaches, including ProteinChip and two-dimensional electrophoresis, were used to identify proteins from serially collected rat serum samples. By both ProteinChip and two-dimensional electrophoresis techniques, the level of a 27-kDa protein was found to be augmented in serum samples during tumor development, decreased after left lobectomy, and reincreased at the time of tumor recurrence. The protein was identified to be brain-derived neurotrophic factor (BDNF). By using specific primers and monoclonal antibody, the expression pattern of BDNF was confirmed in tumor tissue but not in the adjacent nontumorous liver tissue. In addition, the truncated isoform of BDNF receptor-tyrosine protein kinase receptor B was only found in tumor tissue. An in vitro study showed that exogenous BDNF could induce tumor cell proliferation predominantly in relatively small numbers of inoculated cells. Administration of BDNF to tumor cell lines induced significantly increased expression of heat shock protein 90 (Hsp90) and cyclin D1, and blocking the activity of Hsp90 could reverse the up-regulation of cyclin D1 induced by BDNF. The present study revealed that BDNF and its receptor were uniquely expressed in tumor tissue and cell lines of hepatocellular carcimona but not in nontumorous liver tissue and normal cell line. BDNF could stimulate tumor cell proliferation in a Hsp90-dependent manner.

Animals↗
PubMed1985

Computed tomographic analysis of the effects of hyperosmolar mannitol and methylprednisolone on myocardial infarct size.

Using contrast-enhanced computed tomography, the effects of hyperosmolar mannitol and methylprednisolone on experimentally produced myocardial infarcts were evaluated serially over the course of approximately 1 month. Infarct size, initial perfusion defect (jeopardized segment) and noninfarcted muscle mass were determined in three groups of conditioned mongrel dogs. Group 1 (n = 11) served as the control group, groups 2 and 3 were pretreated with mannitol (375 mg/kg, n = 10) or methylprednisolone (7.5 mg/kg, n = 11). Each animal in the treatment groups was treated with identical doses of the originally administered agent twice daily for 7 days after coronary occlusion. Each group developed increases in the noninfarcted muscle mass of the left ventricle (compensatory hypertrophy). The mean increase averaged more than 20% over 30 days when all groups were included together. Infarct size was smaller in both of the treatment groups. However, at 4 days after infarction, mannitol-treated dogs had a mean infarct size that was 68 +/- 8% (+/- standard error of the mean) of the size of control infarcts (p less than 0.01) and methylprednisolone-treated dogs had a mean infarct size that was 77 +/- 6% of the size of control infarcts (p less than 0.01) (referenced to the initial perfusion defect). At 30 days, these differences were less substantial (though still significant), 88 +/- 4% and 85 +/- 5%, respectively. Pharmacologic interventions can be shown to alter the size of an acute myocardial infarction, particularly when examined over the time course of infarct healing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Does the assessment of serum markers in patients with lung cancer aid in the clinical decision making process?

This survey describes potential clinical applications of the tumour markers CYFRA 21-1, SCC antigen, NSE, and CEA in patients with lung cancer. Due to the rather low prevalence of bronchogenic carcinoma in the general public and the limited diagnostic accuracy, currently available tumour markers are unsuitable for the screening of asymptomatic individuals. All studies performed so far in patients with histologically confirmed NSCLC, agree that the best performance characteristics, in terms of sensitivity and specificity, were obtained with the CYFRA 21-1 test (sensitivity: 40-66%, specificity: 95% versus patients with benign pulmonary disorders) while NSE was found to be the marker of first choice in patients with SCLC (sensitivity: 77-85%). For diagnostic purpose, the value of tumour markers must be compared with the efficiency of standard clinical methods including imaging techniques and cytopathological examinations (detection rates: sputum cytology: 40-70%, biopsy at bronchoscopy in central tumours: 95-98%, biopsy at bronchoscopy + bronchial washing + thin needle aspiration in peripheral tumours: 85%). These figures show that the diagnostic yield of cytopathological examinations by far exceeds that of tumour markers. In addition, these investigations supply with histology and give informations on the T-stage (bronchoscopy). Tumour markers, however, may be used for diagnosis in advanced stages in which patients are very often not eligible for extensive investigations due to their performance status. In the differential diagnosis between NSCLC and SCLC a combination of CYFRA 21-1 and NSE was claimed to be helpful. It was demonstrated that 97% of patients could be correctly classified. NSE was shown to be useful to distinguish SCLC from malignant lymphoma, both the Hodgkin's (rate of false-positive elevations: 6.5%) and the non-Hodgkin's (rate of false positive elevations: 22.4%) types. By applying a cut-off point of NSE assays of 21.9 ng/ml corresponding to a 95% specificity versus the lymphoma group, SCLC is still indicated by elevated NSE levels with a sensitivity of 57.7%. Although a positive correlation of marker concentrations with increasing anatomical tumour extent could be demonstrated, the markers cannot be used for staging purposes due to a considerable overlap of marker levels between the individual stages. CYFRA 21-1 was shown to be unable to differentiate between operable (TNM I-IIIa) and inoperable (TNM IIIb/IV) NSCLC patients. The latter were identified with a detection rate of only 17% by the CYFRA 21-1 test (specificity 95% versus operable patients, cut-off point 20 ng/ml). Pretreatment-measured tumour markers, in particular CYFRA 21-1, were shown to provide prognostic information for the overall survival. The negative prognostic effect of CYFRA-21-1 was independent of classical prognostic markers such as performance status and tumour extent. There are several potential applications of serially-assessed tumour markers for disease monitoring of patients under therapy. In SCLC, increasing NSE levels within the remission phase were demonstrated to be strongly suggestive of tumour recurrence. This finding should give rise to further diagnostic procedures. NSE, however, was not able to differentiate between partial and complete remission since, in both cases, NSE levels dropped to the normal range; thus, NSE cannot replace clinical response evaluations. In NSCLC, it was found that curative surgery resulted in a significant drop of preoperatively elevated CYFRA 21-1 or SCC antigen levels down to the normal range. Although rising SCC antigen levels in the postoperative surveillance of patients with squamous cell carcinoma indicated very early tumour relapse, these results are of minor clinical utility due to the absence of curative therapy. Serial measurement of CYFRA 21-1 during chemotherapy in patients with inoperable squamous cell carcinoma has shown that there is a concordance of 74% between the course of the m

Biomarkers, Tumor↗
PubMed2002

Silencing of B cell receptor signals in human naive B cells.

To identify changes in the regulation of B cell receptor (BCR) signals during the development of human B cells, we generated genome-wide gene expression profiles using the serial analysis of gene expression (SAGE) technique for CD34(+) hematopoietic stem cells (HSCs), pre-B cells, naive, germinal center (GC), and memory B cells. Comparing these SAGE profiles, genes encoding positive regulators of BCR signaling were expressed at consistently lower levels in naive B cells than in all other B cell subsets. Conversely, a large group of inhibitory signaling molecules, mostly belonging to the immunoglobulin superfamily (IgSF), were specifically or predominantly expressed in naive B cells. The quantitative differences observed by SAGE were corroborated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. In a functional assay, we show that down-regulation of inhibitory IgSF receptors and increased responsiveness to BCR stimulation in memory as compared with naive B cells at least partly results from interleukin (IL)-4 receptor signaling. Conversely, activation or impairment of the inhibitory IgSF receptor LIRB1 affected BCR-dependent Ca(2+) mobilization only in naive but not memory B cells. Thus, LIRB1 and IL-4 may represent components of two nonoverlapping gene expression programs in naive and memory B cells, respectively: in naive B cells, a large group of inhibitory IgSF receptors can elevate the BCR signaling threshold to prevent these cells from premature activation and clonal expansion before GC-dependent affinity maturation. In memory B cells, facilitated responsiveness upon reencounter of the immunizing antigen may result from amplification of BCR signals at virtually all levels of signal transduction.

Antigens, CD34↗
PubMed1996

The influence of volume therapy and pentoxifylline infusion on circulating adhesion molecules in trauma patients.

Adhesion molecules appear to play a pivotal role in tissue damage secondary to the inflammatory process. Besides neutrophil- and endothelial-bound adhesion molecules, soluble forms have been detected in the circulating blood. They seem to be good markers of endothelial damage, but they may also have other biological functions. Plasma concentrations of soluble adhesion molecules (endothelial leucocyte adhesion molecules (sELAM-1), intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and granule membrane protein 140 (sGMP-140) were serially measured over 5 days by enzyme-linked immunosorbent assays (ELISA) in 45 consecutive trauma patients. These received, by random allocation, only either hydroxyethylstarch solution 10% (mean molecular weight 200,000 daltons) (n = 15) or human albumin 20% (n = 15) for volume therapy. Another 15 patients without defined volume therapy received pentoxifylline continuously (1.2 mg.kg-1.h-1). Measurements were carried out on the day of admission to the intensive care unit (baseline) and during the next 5 days. At baseline, plasma concentrations of all adhesion molecules were similar in all groups. In the hydroxyethyl starch group, sELAM-1 and sICAM-1 concentrations decreased significantly (p < 0.05) reaching normal values during the study period whereas the mean (SD) values increased in the pentoxifylline group (sELAM-1: 71.1 (16.7) to 91.6 (17.8) ng.ml-1) and the albumin group (sICAM-1: 400 (81) to 749 (101) ng.ml-1) (p < 0.05). sVCAM-1 increased outside the normal range only in the human albumin group (to 760 +/- 69 ng.ml-1) (p < 0.05). sGMP-140 plasma concentration increased only in those receiving albumin (432 (85) to 550 (93) ng.ml-1) and this was significantly different to the other groups (p < 0.05). None of the other haemodynamic or laboratory factors could be correlated with plasma concentrations of the adhesion molecules. We conclude that volume therapy with hydroxyethyl starch resulted in a decrease in circulating adhesion molecules in our trauma patients. In contrast, volume therapy with albumin did not exert this effect. Continuous infusion of pentoxifylline did not have a beneficial modulating action on circulating adhesion molecules.

Adult↗
PubMed2006

Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells.

Recent evidence indicates that cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) are involved in hepatocarcinogenesis. This study was designed to evaluate the possible interaction between the COX-2 and EGFR signaling pathways in human hepatocellular carcinoma (HCC) cells. Immunohistochemical analysis using serial sections of human HCC tissues revealed positive correlation between COX-2 and EGFR in HCC cells (P < 0.01). Overexpression of COX-2 in cultured HCC cells (Hep3B) or treatment with PGE(2) or the selective EP(1) receptor agonist, ONO-DI-004, increased EGFR phosphorylation and tumor cell invasion. The PGE(2)-induced EGFR phosphorylation and cell invasiveness were blocked by the EP(1) receptor siRNA or antagonist ONO-8711 and by two EGFR tyrosine kinase inhibitors, AG1478 and PD153035. The EP(1)-induced EGFR transactivation and cell invasion involves c-Src, in light of the presence of native binding complex of EP(1)/Src/EGFR and the inhibition of PGE(2)-induced EGFR phosphorylation and cell invasion by the Src siRNA and the Src inhibitor, PP2. Further, overexpression of COX-2 or treatment with PGE(2) also induced phosphorylation of c-Met, another receptor tyrosine kinase critical for HCC cell invasion. Moreover, activation of EGFR by EGF increased COX-2 promoter activity and protein expression in Hep3B and Huh-7 cells, whereas blocking PGE(2) synthesis or EP(1) attenuated EGFR phosphorylation induced by EGF, suggesting that the COX-2/PGE(2)/EP(1) pathway also modulate the activation of EGFR by its cognate ligand. These findings disclose a cross-talk between the COX-2/PGE(2)/EP(1) and EGFR/c-Met signaling pathways that coordinately regulate human HCC cell invasion.

Alprostadil↗
PubMed1997

The influence of acute preoperative plasmapheresis on coagulation tests, fibrinolysis, blood loss and transfusion requirements in cardiac surgery.

OBJECTIVE: Withdrawal of autologous plasma and reinfusion after cardiopulmonary bypass (CPB) offers the opportunity of improving patients' haemostasis and reducing homologous blood consumption in cardiac surgery. The influence of acute, preoperative plasmapheresis (APP) on coagulation tests, fibrinolysis, blood loss and transfusion requirements was investigated in elective aortocoronary bypass patients. METHODS: Forty patients were randomized to a control or pheresis group. The pheresis group had platelet-rich plasmapheresis (PRP-group, n = 20) performed before incision and the platelet-rich plasma (PRP) was returned after CPB. The control group (n = 20) was managed without pheresis. All patients had serial coagulation studies, including prothrombin split products (F1/F2), fibrinopeptide A (FPA), protein C (PC), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide B beta 15-42 (FPB beta 15-42), haemoglobin and platelet counts determined intra- and postoperatively. Chest tube drainage and transfusion requirements were recorded. RESULTS: APP had no negative effects on the quality of PRP. The platelet count of the withdrawn autologous plasma was 239 +/- 33 x 10(9)/l. From the end of the operation (after retransfusion of autologous plasma) until the first postoperative day platelet counts were significant higher in the PRP-group (P > 0.05). Plasma concentrations of modified antithrombin III (ATM), F1/F2 and FPA increased (166-290% from baseline) and PC- and TM-antigen decreased (11-49% from baseline) to a different extent for both groups throughout CPB. t-PA-activity increased intraoperatively peaking at the end of CPB (PRP-group: 4.8 +/- 0.8 IU/ml, control-group: 8.1 +/- 2.3 IU/ml)(P > 0.05). With onset of CPB PAI-1 levels decreased and were further reduced after CPB in control patients in comparison to PRP-patients (P < 0.05). FPB beta 15-42 occurred in peak concentrations after neutralisation of heparin by protamine. Only PRP-patients showed baseline values of coagulation and fibrinolytic parameters on the next morning (P < 0.05). Total postoperative blood loss during the first 24 h was 503 +/- 251 ml (PRP-group) and 937 +/- 349 ml in the control-group (P < 0.05). None of the PRP-patients received allogeneic blood, whereas five control-patients received 11 units of packed red cells (P < 0.05). CONCLUSIONS: The findings suggest that in elective cardiac surgery heparin cannot prevent generation of both thrombin and fibrin, born throughout CPB and postoperatively. The use of PRP withdrawn immediately preoperatively is an attractive technique to reduce allogeneic blood usage and preoperative blood loss, especially in patients in whom withdrawal of autologous whole blood cannot be performed.

Aged↗
PubMed1997

Does age influence circulating adhesion molecules in the critically ill?

OBJECTIVE: Soluble adhesion molecules are regarded to be markers of inflammation, endothelial activation, or damage. The influence of age on plasma concentrations of circulating adhesion molecules should be serially studied in critically ill intensive care patients. DESIGN: Prospective and descriptive study over 5 days. SETTING: Clinical investigation in a surgical intensive care unit of a university hospital. PATIENTS: Thirty critically ill patients (Acute Physiology and Chronic Health Evaluation [APACHE] II score of > 15 points), with sepsis secondary to postoperative complications, were included in this study. Fifteen consecutive patients aged < 50 yrs and 15 consecutive patients aged > 70 yrs were prospectively studied. INTERVENTIONS: All patients were treated by the standard protocols of our intensive care unit, which did not differ between the groups. The patients received continuous analgesia-sedation and mechanical ventilation. Intensivists caring for the patients were not involved in the study and were blinded to data analysis. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were extensively monitored in all patients. From arterial blood samples, plasma concentrations of soluble adhesion molecules (endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, granule membrane protein-140) were measured on the day of admission (i.e., baseline values) and during the following 5 days. Three of the younger patients and six of the elderly patients died during the study period (p < .05). Oxygen delivery and consumption, and the other hemodynamic data, were without group differences throughout the study. Plasma concentrations of all adhesion molecules were beyond normal at baseline in both groups. These concentrations increased further during the first 2 to 3 days in both groups, with a significantly higher increase in the elderly patients (endothelial leukocyte adhesion molecule-1 to 179 +/- 32 ng/mL; intercellular adhesion molecule-1 to 1695 +/- 158 ng/mL; vascular cell adhesion molecule-1 to 1395 +/- 212 ng/mL; and granule membrane protein-140 to 888 +/- 119 ng/mL). In the younger patients, concentrations of soluble adhesion molecules decreased later in the study and almost reached baseline values on day 5. In the elderly patients, these concentrations remained significantly higher until the end of the study. CONCLUSIONS: The higher plasma concentrations of the measured adhesion molecules in elderly critically ill patients indicate that elderly patients are more prone than younger patients to a more pronounced activation or even damage of the endothelium. Further work needs to be done to determine the prognostic importance and to define the role of soluble adhesion molecules, particularly in the elderly critically ill patient.

Adult↗
PubMed1997

Does continuous heparinization influence platelet function in the intensive care patient?

OBJECTIVE: To study the influence of continuous administration of heparin on platelet function in intensive care patients. DESIGN: Prospective, serial investigation. SETTING: Clinical investigation on a surgical and neurosurgical intensive care unit in a university hospital. PATIENTS: The study included 45 patients: 15 postoperative with patients sepsis (Acute Physiology and Chronic Health Evaluation II score between 15 and 25), 15 trauma patients (Injury Severity Score 15 to 25), and 15 neurosurgical patients. INTERVENTIONS: Management of the patients was carried out according to the guidelines for modern intensive care therapy. Sepsis and trauma patients received standard (unfractionated) heparin continuously [aim: an activated partial thromboplastin time (aPTT) approximately 2.0 times normal value; sepsis-heparin and trauma-heparin patients], whereas neurosurgical patients received no heparin (neurosurgical patients). MEASUREMENTS AND RESULTS: From arterial blood samples, platelet aggregation was measured by the turbidimetric method. Platelet aggregation was induced by adenosine diphosphate (ADP; 2.0 mumol/l), collagen (10 micrograms/ml), and epinephrine (25 mumol/l). Measurements were carried out on the day of diagnosis of sepsis or 12 h after hemodynamic stabilization (trauma and neurosurgery patients) (baseline) and during the next 5 days at 12.00 noon. Standard coagulation parameters [platelet count and fibrinogen and antithrombin III (AT III) plasma concentrations] were also monitored. Heparin 4-10 U/kg per h (mean dose: approximately 500 U/h) was necessary to reach an aPTT of about 2.0 times normal. Platelet count was highest in the neurosurgical patients, but it did not decrease after heparin administration to the trauma and sepsis patients. AT III and fibrinogen plasma levels were similar in the three groups of patients. In the sepsis group, platelet aggregation variables decreased significantly (e.g., epinephrine-induced maximum platelet aggregation:-45 relative % from baseline value). Platelet function recovered during the study and even exceeded baseline values (e.g., ADP-induced maximum platelet aggregation: +42.5 relative % from baseline value). Continuous heparinization did not blunt this increase of platelet aggregation variables. In the heparinized trauma patients, platelet aggregation variables remained almost stable and were no different to platelet aggregation data in the untreated neurosurgical patients. CONCLUSIONS: Continuous administration of heparin with an average dose of approximately 500 U/h did not negatively influence platelet function in the trauma patients. Recovery from reduced platelet function in the sepsis group was not affected by continuous heparinization. Thus, continuous heparinization with this dose appears to be safe with regard to platelet function in the intensive care patient.

APACHE↗
PubMed2002

Serial assessment of mortality in the neonatal intensive care unit by algorithm and intuition: certainty, uncertainty, and informed consent.

OBJECTIVES: Does predictive power for outcomes of neonatal intensive care unit (NICU) patients get better with time? Or does it get worse? We determined the predictive power of Score for Neonatal Acute Physiology (SNAP) scores and clinical intuitions as a function of day of life (DOL) for newborn infants admitted to our NICU. METHODS: We identified 369 infants admitted to our NICU during 1996-1997 who required mechanical ventilation. We calculated SNAP scores on DOL 1, 3, 4, 5, 7, 10, 14, 21, 28, and weekly thereafter until either death or extubation. We also asked nurses, residents, fellows, and attendings on each day of mechanical ventilation: "Do you think this child is going to live to go home to their family, or die before hospital discharge?" RESULTS: Two thousand twenty-eight SNAP scores were calculated for 285 infants. On DOL 1, SNAP for nonsurvivors (24 +/- 8.7 [standard deviation]) was significantly higher than SNAP for survivors (13 +/- 6.1). However, this difference diminished steadily and by DOL 10 was no longer statistically significant (12.7 +/- 4.9 vs 10.0 +/- 4.8). On each NICU day, at all ranges of SNAP scores, there were at least as many infants who would ultimately survive as would die. Consequently, the positive predictive value of any SNAP value for subsequent mortality was <0.5 on all NICU days. Prediction profiles were obtained for 230 ventilated infants reflecting over 11 000 intuitions obtained on 2867 patient days. One hundred fifty-seven (81%) of 192 survivor profiles displayed consistent accurate prediction profiles-at least 90% of their NICU ventilation days were characterized by 100% prediction of survival. Twenty-five (13%) of 192 surviving infants survived somewhat unexpectedly; that is, after at least 1 day characterized by at least 1 estimate of "death." Thirty-three (60%) of the 55 nonsurvivors died before DOL 10. Eighty-two percent of the prediction profiles for these early dying infants were homogeneous, dismal, and accurate. Twenty-two (40%) of the 55 nonsurvivors died after DOL 10. Seventeen (78%) of these 22 late-dying infants were predicted to live by many observers on many hospital days. Sixty-one (30%) of 230 profiled patients had at least 1 NICU day characterized by at least 1 prediction of death; 26/61 (43%) of these patients were incorrectly predicted; that is, they survived. Seventeen infants who were predicted to die during but survived nonetheless were assessed neurologically at 1 year. Fourteen (82%) of these 17 were not neurologically normal-8 were clearly abnormal, 1 suspicious, and 5 had died. CONCLUSIONS: If absolute certainty about mortality is the only criterion that can justify a decision to withhold or withdraw life-sustaining treatment in the NICU, these data would make such decisions difficult on the first day of life, and increasingly problematic thereafter. However, if we acknowledge that medicine is inevitably an inexact science and that clinical predictions can never be perfect, we can ask the more interesting question of whether good but less-than-perfect predictions of imprecise but ethically relevant clinical outcomes can still be useful. We think that they can-and that they must.

Age Factors↗
PubMed2001

Does age affect liver function and the hepatic acute phase response after major abdominal surgery?

OBJECTIVE: The liver plays a key role in the inflammatory response during major surgery or infection. The influence of age on liver function and hepatic acute phase protein (APP) synthesis should be serially studied in elderly patients undergoing major abdominal surgery. DESIGN AND SETTING: Prospective and descriptive study over 3 days. Clinical investigation in the operating room and surgical intensive care unit (ICU) of a tertiary care hospital. PATIENTS AND INTERVENTIONS: 42 consecutive patients were grouped according to age: less than 60 years ("adult") or over 65 years ("elderly") and prospectively studied. All patients received standardized general anesthesia and were treated afterwards according to the standard protocols of our ICU. Intensivists caring for the patients were not involved in the study and were blinded to data analysis. MEASUREMENTS AND RESULTS: Concentrations of interleukin (IL)-6, serum amyloid A (SAA), C-reactive protein (CRP), alpha1-antitrypsin (alpha1-AT), and haptoglobin were measured to assess the APP response. Liver function was evaluated by the monoethylglycinexylidide (MEGX) test and by measuring alpha-glutathione S-transferase (alpha-GST). All measurements were performed at induction of anesthesia (T0), at the end of surgery (T1), and 2 h (T2), 24 h (T3), and 48 h (T4) postoperatively. There was no difference in the incidence of postoperative septic complications between the two groups. Baseline values of IL-6 and the four APPs were normal in all patients and did not differ between the groups. IL-6 levels increased significantly in all patients at T1 and T2, with a significantly higher increase in the older patients (elderly: from 7.4+/-3.4 pg/ml to 220.6+/-49.5 pg/ml; adult: from 6.2+/-2.5 pg/ml to 189.9+/-36.8 pg/ml). A return to baseline values was seen at T3 in both groups. Concentrations of all APPs, except for haptoglobin, started to increase at T3. Peak concentrations were significantly lower in the elderly patients (elderly: SAA 358+/-133 microg/l, CRP 5.1+/-2.3 mg/dl, alpha1-AT 160+/-96 mg/dl; adult: SAA 444+/-100 microg/l, CRP 8.5+/-3.2 mg/dl, alpha1-AT 223+/-85 mg/dl). Baseline alpha-GST and MEGX concentrations were normal in all patients. Alpha-GST concentrations increased in both groups at T1 and T2, with a significantly higher increase in the older patients (elderly: 3.7+/-1.4 microg/l to 10.2+/-2.9 microg/l; adult 4.5+/-2.1 microg/l to 8.5+/-1.7 microg/l). A return to baseline values was seen at T3 in both groups. MEGX concentrations were significantly lower and abnormal (<50 ng/ml) in the older patients at T3 and T4. CONCLUSIONS: Our observations suggest that the postoperative hepatic acute phase response is reduced in elderly patients undergoing major abdominal surgery. The decreased release of liver-synthesized APPs was associated with an impaired hepatocyte function and a disturbance of hepatocellular integrity. Further work needs to be done to determine whether these findings might have an impact on the incidence of postoperative septic complications or prognostic significance for survival in aged patients.

Abdomen↗