1545
shunt
Serum interleukin 10. )L-10=interteukir) 10,
6, detectable
serum
MM= multiple myeloma.
levels of which
are
associated with poor
prognosis, detectable serum interleukin 10 is associated with a good prognosis. It will be of interest to find out the source of the interleukin 10, especially whether it originates from myeloma cells, because B cells can produce this cytokine.8 Alternatively, interleukin 10 may originate from reactive monocytes/ macrophages9 or T cells. to The good prognosis associated with these samples positive for interleukin 10 raises the question of the role of cytokine in this B-cell neoplasia. Studies on freshly isolated myelomatous bone-marrow samples should provide the answers. this
Pierre Merville receives
a
grant from the Foundation Mérieux.
Laboratory for Immunological Research Schering-Plough, Dardilly; Laboratoire d’Oncogénèse; and Laboratory of Immunohaematological Oncology, Institute of Biology, 44035 Nantes, France
P. MERVILLE F. ROUSSET J. BANCHEREAU B. KLEIN R. BATAILLE
1. Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 1988; 332: 83-85. 2. Klein B, Zhang X-G, Jourdan M, et al. A paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. Blood 1989; 73: 517-26. 3. Klein B, Wijdenes J, Zhang X-G, et al. Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood 1991; 78: 1198-204. 4. Bataille R, Jourdan M, Zhang X-G, Klein B. Serum levels of interleukin-6, a potent myeloma cell growth factor, as a reflect of disease severity m plasma cell dyscrasias. J Clin Invest 1989; 84: 2008-1 1. 5. Ludwig H, Bachbaur DM, Friz E, Krainer M, et al. Interleukin-6 is a prognostic factor in multiple myeloma. Blood 1991; 78: 794-95. 6. Rousset F, Garcia E, Defrance T, et al. Interleukin-10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 1992; 89: 1890-93. 7. Durie BGM, Salmon SE. A clinical staging system for multiple myeloma. Cancer
1975; 36: 842-54. 8. O’Garra A,
Stapleton G, Dhar Y, et al. Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol 1990; 2: 821. 9. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209-20. 10. Yieira P, de Waal-Malefyt R, Dang MN, et al. Isolation and expression of human cytokine synthesis inhibitory factor (CSIF/IL-10) cDNA clones: homology to Epstein-Barr virus open reading frame BCRF1. Proc Natl Acad Sci USA 1991; 88: 1172-76.
Inhaled nitric oxide for postoperative pulmonary hypertension in patients with congenital heart defects SIR,-Nitric oxide (NO) is effective in the treatment of pulmonary hypertension in adults. Dr Roberts, Dr Kinsella, and their colleagues (Oct 3, pp 818, 819) report NO administration in persistent pulmonary hypertension of the newborn (PPHN). We have used this agent in life-threatening pulmonary hypertension in patients with congenital heart defects. NO is increasingly used in our institution in children developing severe postoperative pulmonary hypertension. An 18-month-old boy born with transposition of the great arteries and very small ventricular septal defect (VSD) had undergone a Senning operation at 3 months of age. A right-to-left
through the VSD was subsequently noted. Pulmonary hypertension developed later because of pulmonary venous channel stenosis. An arterial switch procedure was done (without VSD closure). At the end of cardiopulmonary bypass, mean right ventricular pressure was about half the systemic pressure (25 mm Hg) with 5 Jlg kg-l min-1 of dopamine and dobutamine and an inspired oxygen fraction of 100%. Progressive suprasystemic pulmonary hypertension was recorded during the early postoperative period. Mean aortic pressure remained unchanged but important hypoxaemia occurred (82%). NO alone was continuously administered as a pulmonary vasodilator for 10 days at various concentrations to reduce the hypertension. Blood pressure, pulmonary venous pressure, left atrial pressure, central venous pressure, SvOz, Sp02’ NO, and N02 concentrations were continuously monitored. Blood gas analysis, including methaemoglobinaemia measurement, was done every 4 h. During the whole period of mechanical ventilation, NO gas (200 parts per million [ppm] in Nz) was given and its concentration was measured through the inspiratory part of the ventilator within the endotracheal tube. During weaning from ventilation, NO was given by an aerosol, in relation to PAP, Sv02, and Sp02 values, and inspired NO concentrations were measured by a nasopharyngeal probe with an electrochemical device (Polytron, Draeger). After extubation, because PAP remained raised, NO was given by means of a facial mask. At baseline, PAP was equal to systemic pressure (72/40 mm Hg, mean 60), Sv02 was 45%, and Sp02 80%. During continuous administration of NO, at concentrations ranging from 5 to 20 ppm, PAP decreased below 60% of blood pressure. SpO2 increased by up to 100% and Sv02 by up to 70%, allowing weaning from mechanical ventilation and extubation 48 h after operation. No further decrease in PAP was noted, even with higher NO concentrations. We tried every 3 hours to discontinue NO, but our efforts resulted in an increase in PAP with a decrease in SpOz and SvOz: an echocardiogram showed a left-to-right shunt through the VSD. This shunt became right-to-left 2 min after NO was discontinued. Re-administration of NO reversed the direction of this shunt after 20 s delay. Methaemoglobinaemia concentration did not exceed 1-3%. No neurological abnormality was noted, apart from an unexplained but moderate tendency to somnolence. Physiological activity of endogenous NO is indicated by the decline in pulmonary vascular resistance at birth. We have recorded in older children the constant vasodilatory effect seen in adults.’1 Pulmonary hypertension occurs in patients with congenital heart disease if there is high pulmonary blood flow or post-capillary obstruction. These situations are often associated with severe histological vascular changes,3 but the cellular mechanism for these changes is still poorly defined. Abnormalities in endothelin-derived relaxing factor or endothelin release have been suggested.’,4 However, this mechanism seems to persist and to increase several days after complete surgical correction and removal of the cause of pulmonary hypertension. In our patient the contribution of the left-to-right shunt to pulmonary hypertension was negligible compared with that of post-capillary obstruction, and was easily reversed by NO inhalation without any tachyphylaxia. Furthermore, NO allowed rapid weaning from mechanical ventilation that we have not seen with traditional treatments. NO has wide potential use after surgery for congenital cardiac conditions, but we agree with Roberts and Kinsella that better knowledge of its toxicity is required. AYMAN HAYDAR THIERRY MALHERE Departments of Anaesthesia PHILIPPE MAURIAT DIDIER JOURNOIS Intensive Care Medicine, PHILIPPE POUARD NOËL DENIS and Cardiac Surgery, DIDIER LEFÈBVRE DENIS SAFRAN Hôpital Laennec, PASCAL VOUHÉ 75007 Paris, France 1.
Pepke-Zaba J, Higenbottam T, Dinh-Zuan A. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 1991; 338:
1173-74. 2. Abman S, Chatfield B, Hall S, McMurtry I. Role of EDRF during transition of pulmonary circulation at birth. Am J Physiol 1990; 259: H1921-27. 3. Meyrick B, Reid L. Ultrastructural findings in lung biopsy material from children with congenital heart defects. Am J Pathol 1980; 101: 527-42. 4. Yoshibayashi M, Nishioka K, Nakao K, et al. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Circulation 1991; 84: 2280-85.
shunt
Serum interleukin 10. )L-10=interteukir) 10,
6, detectable
serum
MM= multiple myeloma.
levels of which
are
associated with poor
prognosis, detectable serum interleukin 10 is associated with a good prognosis. It will be of interest to find out the source of the interleukin 10, especially whether it originates from myeloma cells, because B cells can produce this cytokine.8 Alternatively, interleukin 10 may originate from reactive monocytes/ macrophages9 or T cells. to The good prognosis associated with these samples positive for interleukin 10 raises the question of the role of cytokine in this B-cell neoplasia. Studies on freshly isolated myelomatous bone-marrow samples should provide the answers. this
Pierre Merville receives
a
grant from the Foundation Mérieux.
Laboratory for Immunological Research Schering-Plough, Dardilly; Laboratoire d’Oncogénèse; and Laboratory of Immunohaematological Oncology, Institute of Biology, 44035 Nantes, France
P. MERVILLE F. ROUSSET J. BANCHEREAU B. KLEIN R. BATAILLE
1. Kawano M, Hirano T, Matsuda T, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 1988; 332: 83-85. 2. Klein B, Zhang X-G, Jourdan M, et al. A paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. Blood 1989; 73: 517-26. 3. Klein B, Wijdenes J, Zhang X-G, et al. Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood 1991; 78: 1198-204. 4. Bataille R, Jourdan M, Zhang X-G, Klein B. Serum levels of interleukin-6, a potent myeloma cell growth factor, as a reflect of disease severity m plasma cell dyscrasias. J Clin Invest 1989; 84: 2008-1 1. 5. Ludwig H, Bachbaur DM, Friz E, Krainer M, et al. Interleukin-6 is a prognostic factor in multiple myeloma. Blood 1991; 78: 794-95. 6. Rousset F, Garcia E, Defrance T, et al. Interleukin-10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 1992; 89: 1890-93. 7. Durie BGM, Salmon SE. A clinical staging system for multiple myeloma. Cancer
1975; 36: 842-54. 8. O’Garra A,
Stapleton G, Dhar Y, et al. Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol 1990; 2: 821. 9. de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209-20. 10. Yieira P, de Waal-Malefyt R, Dang MN, et al. Isolation and expression of human cytokine synthesis inhibitory factor (CSIF/IL-10) cDNA clones: homology to Epstein-Barr virus open reading frame BCRF1. Proc Natl Acad Sci USA 1991; 88: 1172-76.
Inhaled nitric oxide for postoperative pulmonary hypertension in patients with congenital heart defects SIR,-Nitric oxide (NO) is effective in the treatment of pulmonary hypertension in adults. Dr Roberts, Dr Kinsella, and their colleagues (Oct 3, pp 818, 819) report NO administration in persistent pulmonary hypertension of the newborn (PPHN). We have used this agent in life-threatening pulmonary hypertension in patients with congenital heart defects. NO is increasingly used in our institution in children developing severe postoperative pulmonary hypertension. An 18-month-old boy born with transposition of the great arteries and very small ventricular septal defect (VSD) had undergone a Senning operation at 3 months of age. A right-to-left
through the VSD was subsequently noted. Pulmonary hypertension developed later because of pulmonary venous channel stenosis. An arterial switch procedure was done (without VSD closure). At the end of cardiopulmonary bypass, mean right ventricular pressure was about half the systemic pressure (25 mm Hg) with 5 Jlg kg-l min-1 of dopamine and dobutamine and an inspired oxygen fraction of 100%. Progressive suprasystemic pulmonary hypertension was recorded during the early postoperative period. Mean aortic pressure remained unchanged but important hypoxaemia occurred (82%). NO alone was continuously administered as a pulmonary vasodilator for 10 days at various concentrations to reduce the hypertension. Blood pressure, pulmonary venous pressure, left atrial pressure, central venous pressure, SvOz, Sp02’ NO, and N02 concentrations were continuously monitored. Blood gas analysis, including methaemoglobinaemia measurement, was done every 4 h. During the whole period of mechanical ventilation, NO gas (200 parts per million [ppm] in Nz) was given and its concentration was measured through the inspiratory part of the ventilator within the endotracheal tube. During weaning from ventilation, NO was given by an aerosol, in relation to PAP, Sv02, and Sp02 values, and inspired NO concentrations were measured by a nasopharyngeal probe with an electrochemical device (Polytron, Draeger). After extubation, because PAP remained raised, NO was given by means of a facial mask. At baseline, PAP was equal to systemic pressure (72/40 mm Hg, mean 60), Sv02 was 45%, and Sp02 80%. During continuous administration of NO, at concentrations ranging from 5 to 20 ppm, PAP decreased below 60% of blood pressure. SpO2 increased by up to 100% and Sv02 by up to 70%, allowing weaning from mechanical ventilation and extubation 48 h after operation. No further decrease in PAP was noted, even with higher NO concentrations. We tried every 3 hours to discontinue NO, but our efforts resulted in an increase in PAP with a decrease in SpOz and SvOz: an echocardiogram showed a left-to-right shunt through the VSD. This shunt became right-to-left 2 min after NO was discontinued. Re-administration of NO reversed the direction of this shunt after 20 s delay. Methaemoglobinaemia concentration did not exceed 1-3%. No neurological abnormality was noted, apart from an unexplained but moderate tendency to somnolence. Physiological activity of endogenous NO is indicated by the decline in pulmonary vascular resistance at birth. We have recorded in older children the constant vasodilatory effect seen in adults.’1 Pulmonary hypertension occurs in patients with congenital heart disease if there is high pulmonary blood flow or post-capillary obstruction. These situations are often associated with severe histological vascular changes,3 but the cellular mechanism for these changes is still poorly defined. Abnormalities in endothelin-derived relaxing factor or endothelin release have been suggested.’,4 However, this mechanism seems to persist and to increase several days after complete surgical correction and removal of the cause of pulmonary hypertension. In our patient the contribution of the left-to-right shunt to pulmonary hypertension was negligible compared with that of post-capillary obstruction, and was easily reversed by NO inhalation without any tachyphylaxia. Furthermore, NO allowed rapid weaning from mechanical ventilation that we have not seen with traditional treatments. NO has wide potential use after surgery for congenital cardiac conditions, but we agree with Roberts and Kinsella that better knowledge of its toxicity is required. AYMAN HAYDAR THIERRY MALHERE Departments of Anaesthesia PHILIPPE MAURIAT DIDIER JOURNOIS Intensive Care Medicine, PHILIPPE POUARD NOËL DENIS and Cardiac Surgery, DIDIER LEFÈBVRE DENIS SAFRAN Hôpital Laennec, PASCAL VOUHÉ 75007 Paris, France 1.
Pepke-Zaba J, Higenbottam T, Dinh-Zuan A. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 1991; 338:
1173-74. 2. Abman S, Chatfield B, Hall S, McMurtry I. Role of EDRF during transition of pulmonary circulation at birth. Am J Physiol 1990; 259: H1921-27. 3. Meyrick B, Reid L. Ultrastructural findings in lung biopsy material from children with congenital heart defects. Am J Pathol 1980; 101: 527-42. 4. Yoshibayashi M, Nishioka K, Nakao K, et al. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Circulation 1991; 84: 2280-85.
