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150 ABSTRACTS pituitary and stress hormones and selected cytokines. Admin- istration of interleukin-2 resulted in fever, tachyacardia, “flu-like” symptoms, and neurohormonal elaboration. The responses observed were quantitatively similar to those that occurred after endotoxin administration in healthy subjects (n = 13), but differed in the following manner: 1) the onset of fever and endocrine changes occurred after a longer latent interval (180-240 minutes vs. 60-90 minutes after endotox- in), 2) peak responses after the administration of interleukin- 2 also occurred later, 3) no increased circulating tumor necrosis factor was detected after administration of interleu- kin-2 (peak plasma concentration was t35 pg/ml vs. 270 f 70- pg/ml after endotoxin administration), and 4) adminis- tration of interleukin-2 but not of endotoxin was associated with increased circulating concentrations of gamma inter- feron (peak plasma concentration 1.7 + 0.2 NIH U/ml vs. co.1 NIH U/ml after endotoxin administration). Fever and neurohormonal responses after interleukin-2 administration were greatly attenuated by ibuprofen administration. Inter- leukin-2 induces other cytokines that exert their effects largely through the cyclooxygenase pathway. Interleukin-2 may be an important signal, initiating the integrated host responses to infection and injury. (Reprinted with permis- sion.) Tumor Necrosis Factor and Endotoxin Induce Similar Meta- bolic Responses in Human Beings. Michie HR. Spriggs DR, Manogue KR, et al. Surgery 104:280, 1988. After injury, infection, or major operations a number of predictable metabolic responses occur. It has been proposed that the cytokine tumor necrosis factor (TNF)/cachectin is a primary mediator of these host responses. To test this hypoth- esis, we studied 16 tumor-bearing humans with normal renal and hepatic function, who received 24-hour continuous intra- venous infusions of escalating doses of recombinant TNF (4 to 636/pg/m*/24 h). Serial measurements were made of vital signs and plasma concentrations of TNF, interleukin-1, adre- nocorticotropic hormone, cortisol, iron, glucose, and C- reactive protein. Low doses of TNF had minimal metabolic effects, but infusions of ,545 @g/m*/24 hr (n = 8) resulted in fever, pituitary, and stress hormone release and acute phase changes. These alterations were compared with the changes that occurred in healthy humans (n = 13) receiving intravenous bolus injections of Escherichia coli endotoxin (4 rig/kg). TNF infusion in doses 2545 pg/m2/24 hr produced peak plasma TNF concentrations and metabolic responses that were similar to those after endotoxin injection. lnterleu- kin-l concentrations remained basal after TNF or endotoxin administration. TNF may represent the primary afferent signal that initiates many of the metabolic responses asso- ciated with sepsis and endotoxemia. (Reprinted with permis- sion.) Prevention of Colonization and Infection in Critically Ill Patients: A Prospective Randomized Study. Kerver AJH, Rommes JH, Mevissen-Verhage AE, et al. Crit Care Med 16:1087, 1988. In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 inten- sive care patients were randomly allocated into a control group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorga- nisms in the oropharnyx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bac- teria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram- negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics. (Reprinted with permis- sion.) Effects of a Stable Prostacyclin Analog on Experimental lschemic Acute Renal Failure. Tobimatsu M, Ueda U, Saito S, et al. Ann Surg 208:65, 1988. The effect of OP-41483, a stable prostacyclin (PG12) analog, on ischemic acute renal failure (ARF) was investi- gated in dogs. Administration of OP-41483 for three days after ischemia significantly increased renal cortical blood flow (RCBF) when compared with dogs treated with the saline vehicle. In the OP-41483-treated group, serum creati- nine levels remained relatively low during postoperative days l-3 and mean survival time was prolonged. Injection of a silicone rubber vascular casting compound (Microfil) revealed increased numbers of visible renal cortical glomeruli and microvessels compared to the saline vehicle group. Histo- logic sections showed only very limited tubular necrosis, whereas sections of kidneys treated with saline showed exten- sive tubular necrosis. In conclusion, this stable prostacyclin analog provided a significant degree of protection for the kidneys from ischemic injury and may be useful in a clinical- setting. (Reprinted with permission.) Extrascorporeal Membrane Oxygenation for Respiratory and Cardiac Failure in Infants and Children. Redmond CR, Graves ED, Falterman KW. et al. J Thorac Cardiovasc Surg 93:199, 1987. Fifty-three neonates and seven pediatric patients were treated with extracorporeal membrane oxygenation from September 1983 until April 1986. Venoarterial bypass was achieved by cannulating the right atrium via the right internal jugular vein and the aortic arch via the right common carotid artery. In the neonatal group, 40 infants with acute respiratory failure were treated, and 36 (90%) survived. Five infants with congenital heart disease were treated and three (60%) survived. Among the eight patients with congenital diaphragmatic hernia, there were three (38%) survivors. In the pediatric group, four patients were treated for ventricular failure after cardiac operations. Two were weaned from bypass, with one long-term survivor. Three patients with acute respiratory failure were treated, with one survivor. Extracorporeal membrane oxygenation has proved to be a useful modality in salvaging high-risk neonates with minimal morbidity and mortality. It has also been useful in the support of infants with congenital heart disease and congeni-

Prevention of colonization and infection in critically III patients: A prospective randomized study

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150 ABSTRACTS

pituitary and stress hormones and selected cytokines. Admin- istration of interleukin-2 resulted in fever, tachyacardia, “flu-like” symptoms, and neurohormonal elaboration. The responses observed were quantitatively similar to those that occurred after endotoxin administration in healthy subjects (n = 13), but differed in the following manner: 1) the onset of fever and endocrine changes occurred after a longer latent interval (180-240 minutes vs. 60-90 minutes after endotox- in), 2) peak responses after the administration of interleukin- 2 also occurred later, 3) no increased circulating tumor necrosis factor was detected after administration of interleu- kin-2 (peak plasma concentration was t35 pg/ml vs. 270 f 70- pg/ml after endotoxin administration), and 4) adminis- tration of interleukin-2 but not of endotoxin was associated with increased circulating concentrations of gamma inter- feron (peak plasma concentration 1.7 + 0.2 NIH U/ml vs. co.1 NIH U/ml after endotoxin administration). Fever and neurohormonal responses after interleukin-2 administration were greatly attenuated by ibuprofen administration. Inter- leukin-2 induces other cytokines that exert their effects largely through the cyclooxygenase pathway. Interleukin-2 may be an important signal, initiating the integrated host responses to infection and injury. (Reprinted with permis- sion.)

Tumor Necrosis Factor and Endotoxin Induce Similar Meta-

bolic Responses in Human Beings. Michie HR. Spriggs DR, Manogue KR, et al. Surgery 104:280, 1988.

After injury, infection, or major operations a number of predictable metabolic responses occur. It has been proposed that the cytokine tumor necrosis factor (TNF)/cachectin is a primary mediator of these host responses. To test this hypoth- esis, we studied 16 tumor-bearing humans with normal renal and hepatic function, who received 24-hour continuous intra- venous infusions of escalating doses of recombinant TNF (4 to 636/pg/m*/24 h). Serial measurements were made of vital signs and plasma concentrations of TNF, interleukin-1, adre- nocorticotropic hormone, cortisol, iron, glucose, and C- reactive protein. Low doses of TNF had minimal metabolic effects, but infusions of ,545 @g/m*/24 hr (n = 8) resulted in fever, pituitary, and stress hormone release and acute phase changes. These alterations were compared with the changes that occurred in healthy humans (n = 13) receiving intravenous bolus injections of Escherichia coli endotoxin (4 rig/kg). TNF infusion in doses 2545 pg/m2/24 hr produced peak plasma TNF concentrations and metabolic responses that were similar to those after endotoxin injection. lnterleu- kin-l concentrations remained basal after TNF or endotoxin administration. TNF may represent the primary afferent signal that initiates many of the metabolic responses asso- ciated with sepsis and endotoxemia. (Reprinted with permis- sion.)

Prevention of Colonization and Infection in Critically Ill Patients: A Prospective Randomized Study. Kerver AJH, Rommes JH, Mevissen-Verhage AE, et al. Crit Care Med 16:1087, 1988.

In a prospective randomized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections, 96 inten- sive care patients were randomly allocated into a control

group and a study group. The study group received oral nonabsorbable antimicrobial agents (i.e., tobramycin, amphotericin B, and polymyxin E) in addition to parenteral antibiotics. Colonization with Gram-negative microorga- nisms in the oropharnyx, and respiratory and digestive tracts increased in the control group during their stay, while the study group did not tend to colonize with Gram-negative bacteria. In the control group, 107 nosocomial infections were diagnosed, vs. 42 nosocomial infections in the study group. Nosocomial infections caused by Gram-negative bac- teria were significantly less frequent in the study group. Mortality due to an acquired infection was significantly less frequent in the study group. We conclude that colonization, infection, and subsequent mortality by nosocomial Gram- negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics. (Reprinted with permis- sion.)

Effects of a Stable Prostacyclin Analog on Experimental

lschemic Acute Renal Failure. Tobimatsu M, Ueda U, Saito S, et al. Ann Surg 208:65, 1988.

The effect of OP-41483, a stable prostacyclin (PG12) analog, on ischemic acute renal failure (ARF) was investi- gated in dogs. Administration of OP-41483 for three days after ischemia significantly increased renal cortical blood flow (RCBF) when compared with dogs treated with the saline vehicle. In the OP-41483-treated group, serum creati- nine levels remained relatively low during postoperative days l-3 and mean survival time was prolonged. Injection of a silicone rubber vascular casting compound (Microfil) revealed increased numbers of visible renal cortical glomeruli and microvessels compared to the saline vehicle group. Histo- logic sections showed only very limited tubular necrosis, whereas sections of kidneys treated with saline showed exten- sive tubular necrosis. In conclusion, this stable prostacyclin analog provided a significant degree of protection for the kidneys from ischemic injury and may be useful in a clinical- setting. (Reprinted with permission.)

Extrascorporeal Membrane Oxygenation for Respiratory and Cardiac Failure in Infants and Children. Redmond CR, Graves ED, Falterman KW. et al. J Thorac Cardiovasc Surg 93:199, 1987.

Fifty-three neonates and seven pediatric patients were treated with extracorporeal membrane oxygenation from September 1983 until April 1986. Venoarterial bypass was achieved by cannulating the right atrium via the right internal jugular vein and the aortic arch via the right common carotid artery. In the neonatal group, 40 infants with acute respiratory failure were treated, and 36 (90%) survived. Five infants with congenital heart disease were treated and three (60%) survived. Among the eight patients with congenital diaphragmatic hernia, there were three (38%) survivors. In the pediatric group, four patients were treated for ventricular failure after cardiac operations. Two were weaned from bypass, with one long-term survivor. Three patients with acute respiratory failure were treated, with one survivor. Extracorporeal membrane oxygenation has proved to be a useful modality in salvaging high-risk neonates with minimal morbidity and mortality. It has also been useful in the support of infants with congenital heart disease and congeni-