Intermittent positive pressure ventilation with either positive end-expiratory pressure or high frequency jet ventilation (HFJV), or HFJV alone in human acute respiratory failure.

Continuous Positive Pressure Ventilation (CPPV), High-Frequency Jet Ventilation (HFJV), and a combination of HFJV with Intermittent Positive Pressure Ventilation (CV) were randomly compared in 13 critically ill patients with severe acute respiratory failure. Ventilatory settings were chosen in order to apply the same mean airway pressure (Paw) during the three modes. Respiratory frequencies were adjusted during CPPV (16 +/- 2 breaths/min) and HFJV (235 +/- 32 breaths/min) to achieve the same level of PaCO2 and were then combined during CV. All patients were heavily sedated during the study and had had peripheral and balloon-tipped pulmonary arterial catheters previously inserted. After a steady state at FIO2 1 in each mode of ventilation, hemodynamic and respiratory parameters were measured. A Paw of 13.8 +/- 2.9 mm Hg was applied to each patient by using a PEEP of 7.4 mm Hg during CPPV; a driving pressure of 2.9 +/- 0.2 bars and an I/E ratio of 0.43 during HFJV; and by combining HFJV, using a driving pressure of 1.2 +/- 0.3 bars with intermittent positive pressure ventilation during CV. There were no significant differences in any of the hemodynamic or respiratory parameters measured, except for a significant decrease in PaCO2 during CV when compared to CPPV or HFJV. We concluded that 1) arterial oxygenation and cardiac output depend mainly on Paw independent of the method used to increase Paw and 2) CV can improve CO2 elimination without increasing Paw.(ABSTRACT TRUNCATED AT 250 WORDS

Ventilatory effects of continuous epidural infusion of fentanyl.

The effects of a continuous epidural administration of fentanyl on pain and on ventilation were studied in eight patients scheduled for orthopedic surgery of the knee. In each subject, epidural fentanyl was given by a bolus dose of 1 microgram.kg-1, followed by a continuous infusion of 1 microgram.kg-1.h-1 over 18 hours. Ventilatory measurements were performed during quiet breathing and during CO2 stimulation tests before surgery. After surgery measurements were made before epidural administration of fentanyl; 1, 2, 5, 18 hours after the start of epidural fentanyl infusion; and 6 hours after its discontinuation. Adequate pain relief was achieved in all patients during fentanyl administration. No significant change in ventilation was noted during quiet breathing. The slope of the ventilatory response to CO2 (VE/PaCO2) decreased significantly from 1.46 +/- 0.2 to 0.75 +/- 0.1 L.min-1.mm Hg-1 (mean +/- SEM; P less than 0.05) one hour after the onset of fentanyl administration, and remained stable throughout the infusion. Eighteen hours after the onset of epidural fentanyl infusion, VE/PaCO2 was still 0.76 +/- 0.14 L.min-1.mm Hg-1. At the end of fentanyl administration, plasma fentanyl levels measured in six patients had progressively increased from 0.42 +/- 0.02 ng.ml one hour after the onset of the infusion to 1.54 +/- 0.19 ng.ml at the end of the infusion. These results suggest that a continuous epidural administration of fentanyl is a technique of analgesia that can provide adequate pain relief but which is associated with ventilatory depression. However, with the doses used in this study, the ventilatory depression remained moderate and of no demonstrable clinical consequence

Effects of high-frequency jet ventilation on arterial baroreflex regulation of heart rate.

Fifteen anesthetized mechanically ventilated patients recovering from multiple trauma were studied to compare the effects of high-frequency jet ventilation (HFJV) and continuous positive-pressure ventilation (CPPV) on arterial baroreflex regulation of heart rate. Systolic arterial pressure and right atrial pressure were measured using indwelling catheters. Electrocardiogram (ECG) and mean airway pressure were continuously monitored. Lung volumes were measured using two linear differential transformers mounted on thoracic and abdominal belts. Baroreflex testing was performed by sequential intravenous bolus injections of phenylephrine (200 micrograms) and nitroglycerin (200 micrograms) to raise or lower systolic arterial pressure by 20-30 Torr. Baroreflex regulation of heart rate was expressed as the slope of the regression line between R-R interval of the ECG and systolic arterial pressure. In each mode of ventilation the ventilatory settings were chosen to control mean airway pressure and arterial PCO2 (PaCO2). In HFJV a tidal volume of 159 +/- 61 ml was administered at a frequency of 320 +/- 104 breaths/min, whereas in CPPV a tidal volume of 702 +/- 201 ml was administered at a frequency of 13 +/- 2 breaths/min. Control values of systolic arterial pressure, R-R interval, mean pulmonary volume above apneic functional residual capacity, end-expiratory pulmonary volume, right atrial pressure, mean airway pressure, PaCO2, pH, PaO2, and temperature before injection of phenylephrine or nitroglycerin were comparable in HFJV and CPPV. Baroreflex regulation of heart rate after nitroglycerin injection was significantly higher in HFJV (4.1 +/- 2.8 ms/Torr) than in CPPV (1.96 +/- 1.23 ms/Torr).(ABSTRACT TRUNCATED AT 250 WORDS

Characterization of the GAGE genes that are expressed in various human cancers and in normal testis

The GAGE-1 gene was identified previously as a gene that codes for an antigenic peptide, YRPRPRRY, which was presented on a human melanoma by HLA-Cw6 molecules and recognized by a clone of CTLs derived from the patient bearing the tumor. By screening a cDNA library from this melanoma, we identified five additional, closely related genes named GAGE-2-6. We report here that further screening of this library led to the identification of two more genes, GAGE-7B and -8. GAGE-1, -2, and -8 code for peptide YRPRPRRY. Using another antitumor CTL clone isolated from the same melanoma patient, we identified antigenic peptide, YYWPRPRRY, which is encoded by GAGE-3, -4, -5, -6, and -7B and which is presented by HLA-A29 molecules. Genomic cloning of GAGE-7B showed that it is composed of five exons. Sequence alignment showed that an additional exon, which is present only in the mRNA of GAGE-1, has been disrupted in gene GAGE-7B by the insertion of a long interspersed repeated element retroposon. These GAGE genes are located in the p11.2-p11.4 region of chromosome X. They are not expressed in normal tissues, except in testis, but a large proportion of tumors of various histological origins express at least one of these genes. Treatment of normal and tumor cultured cells with a demethylating agent, azadeoxycytidine, resulted in the transcriptional activation of GAGE genes, suggesting that their expression in tumors results from a demethylation process