95 PROSTAGLANDIN E1 FOR INTERRUPTED AORTIC ARCH IN THE NEONATE be used to maintain the SIR,-E-type prostaglandins in neonates with certain ductus arteriosus the of patency heart malformations.’ 2 The reported excongenital cyanotic perience has been exclusively in infants with right-heart obstructive lesions whose survival and arterial oxygen saturation depend on pulmonary blood-flow through a persistent ductus arteriosus.
This
case
seriously
illustrates its potential sick neonates.
as an
initial
D. J. RADFORD K. R. BLOOM F. COCEANI R. FARIELLO P. M. OLLEY
can
We have used prostaglandin E1(r.G.E,) in interruption of the aortic arch. In this malformation, blood-supply to the lower part of the body depends on persistence of the ductus arteriosus, and infants usually die of severe metabolic acidosis and cardiac failure as the ductus closes. If the patient can be maintained medically in a reasonably fit condition, surgical reconstruction of the aortic arch is now feasible.3 The use of the ductal muscle-relaxant effect of prostaglandins seems worthy of trial in this situation.4
After
normal pregnancy and delivery, the male infant 3.8kg and had an Apgar score of 8. A hare lip and subluxation of the left hip were noted, but he was apparently well and was discharged from hospital on the fifth day. On the ninth day he began to vomit and was readmitted. Transfer to our unit was arranged on day 10. a
weighed
approach to these
Department of Pediatrics, Division of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada MSG 1X8
INTRAPLEURAL B.C.G. TREATMENT OF EXPERIMENTAL LUNG TUMOURS
SIR,-Dr McKneally and his colleagues (Feb. 21, p. 377) reported beneficial effects in stage-i lung-cancer patients after postoperative intrapleural administration of B.C.G. Baldwin and I have shown that growth of solid tumours or malignant effusions in the pleural cavity of the rat can be controlled by intrapleural administration of the vaccine.’ In addition, lungtumour deposits can be suppressed by pulmonary infiltration with B.C.G., administered intravenously.23 In view of the clinical findings of McKneally et al. preliminary tests have been carried out to examine experimentally the effect on tumour growth in the lungs of B.c.G. given into the pleural cavity. B.C.G. TREATMENT OF LONG-TUMOUR GROWTH IN RATS
On examination, the baby was very ill with severe cardiac failure. The pulses in the left arm and both femorals were weak to palpation and systolic blood-pressures were 100 mm Hg in the right arm, 68 in the left arm, and 64 in both legs. Digoxin and diuretics were started. At cardiac catheterisation, angiography demonstrated complete interruption of the aortic arch. Flow to the descending aorta was through a patent ductus arteriosus and the left sub-
clavian artery arose from this lower segment. In addition, there was a ventricular septal defect and an atrial defect. The pressures were: right ventricle 100/14 mm Hg, main pulmonary artery 100/55, and descending aorta 55/45. During the procedure bicarbonate was given to correct metabolic acidosis. P.G.EI5 0.11 g/kg/min, was infused directly into the ductus arteriosus via a catheter positioned there from the venous side. Within 10 min, the pressure in the descending aorta rose from 55/45 to 72/46 mm Hg suggesting reopening of the ductus. Simultaneously, the pulmonary-artery pressure fell to 94/50
mm Hg. A cannula was left in the inferior sion continued at 0.03
and p.G.E1 infuthe reduced dose, Despite g/kg/min. the improvement in the general haemodynamic status of the patient was maintained and he began to pass urine. The systolic pressure in his legs remained around 65 mm Hg. However, he developed generalised seizures and eventually entered into status epilepticus. This was attributed to severe hypocalcaemia, and p.G.EI treatment was maintained while the status epilepticus was controlled with anticonvulsants and by correction of the hypocalcaemia. The heemodynamic improvement persisted during p.G.EI treatment, and at the age of 13 days surgical correction under deep hypothermia was scheduled. Unfortunately, the infant developed ventricular fibrillation as his chest was
vena cava
opened and he could not be resuscitated.
At necropsy, the patency of the ductus arteriosus was confirmed along with the interrupted aortic arch and ventricular septal defect.
Although arteriosus is
interruption
the relaxant action of P.G.E, on the ductus striking under hypoxic conditions,4 its use in of the aortic arch has previously been suggested.2
most
Elliott, R. B., Starling, M. B., Neutze, J. M. Lancet, 1975, i, 140. Olley, P M., Coceani, F., Bodach, E. Circulation, 1976, 53, 728 3 Goor, D A, Lillehei, C. W. Congenital Malformations of the Heart, p. 281 New York, 1975. 4 Coceani, F., Olley, P. M. Can. J. Physiol. Pharmac. 1973, 51, 220. 1. 2
I
i
I
*With respect to tumour injection. tFrom Wilcoxon non-parametric rank
i
i
test.
In these tests (see accompanying initiated by intravenous (i.v.)
were
I
table) pulmonary tumours injection of cells from two
syngeneically transplanted tumours in Wistar rats3-methylcholanthrene-induced sarcoma (Mc40A’) and an aminoazodye-induced hepatoma (D23’). Treatment was given by subcutaneous (s.c.) or intrapleural (i.pl.) injection of B.C.G. (Glaxo percutaneous vaccine B.P., 3x 107 viable units/mg moist weight of organisms, representing approximately 20% viability). In the first ten untreated animals survived for 16-23 days, all having to be killed because of extensive pulmonary tumour growth, but a single intrapleural injection of B.C.G. prolonged survival to 24-65 days. Similar results were obtained in two other tests, where the effect of intrapleural B.C.G. significantly prolonged survival, while s.c. injection of the vaccine had a smaller and less consistent effect. These preliminary findings may help to provide a rational basis for treatment of lung tumours by intrapleurally administered B.c.G., the indication being that this route is superior to distant injection. In addition, they provide an experimental model for screening other adjuvants, and for investigating the mechanism of action of intrapleural B.C.G. Previous studies, with subcutaneous tumour growths in rats, have demonstrated that tumour supression by regionally applied B.C.G. depends more upon local activation of host macrophages than upon general immunostimulation,4and further tests are in pro1. 2. 3. 4. 5.
Pimm, M. V., Baldwin, R. W. Int. J. Cancer, 1975, 15, 260. Pimm, M. V., Baldwin, R. W. Br J. Cancer, 1973, 27, 48. Baldwin, R. W., Pimm, M. V. ibid. 1974, 30, 473. Hopper, D. G, Pimm, M. V., Baldwin, R. W. Cancer Immun, 1976, 1, 143. Pimm, M. V., Hopper, D. G. Br. J. Cancer, 1975, 32, 241.
Immunother.
This
case
seriously
illustrates its potential sick neonates.
as an
initial
D. J. RADFORD K. R. BLOOM F. COCEANI R. FARIELLO P. M. OLLEY
can
We have used prostaglandin E1(r.G.E,) in interruption of the aortic arch. In this malformation, blood-supply to the lower part of the body depends on persistence of the ductus arteriosus, and infants usually die of severe metabolic acidosis and cardiac failure as the ductus closes. If the patient can be maintained medically in a reasonably fit condition, surgical reconstruction of the aortic arch is now feasible.3 The use of the ductal muscle-relaxant effect of prostaglandins seems worthy of trial in this situation.4
After
normal pregnancy and delivery, the male infant 3.8kg and had an Apgar score of 8. A hare lip and subluxation of the left hip were noted, but he was apparently well and was discharged from hospital on the fifth day. On the ninth day he began to vomit and was readmitted. Transfer to our unit was arranged on day 10. a
weighed
approach to these
Department of Pediatrics, Division of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada MSG 1X8
INTRAPLEURAL B.C.G. TREATMENT OF EXPERIMENTAL LUNG TUMOURS
SIR,-Dr McKneally and his colleagues (Feb. 21, p. 377) reported beneficial effects in stage-i lung-cancer patients after postoperative intrapleural administration of B.C.G. Baldwin and I have shown that growth of solid tumours or malignant effusions in the pleural cavity of the rat can be controlled by intrapleural administration of the vaccine.’ In addition, lungtumour deposits can be suppressed by pulmonary infiltration with B.C.G., administered intravenously.23 In view of the clinical findings of McKneally et al. preliminary tests have been carried out to examine experimentally the effect on tumour growth in the lungs of B.c.G. given into the pleural cavity. B.C.G. TREATMENT OF LONG-TUMOUR GROWTH IN RATS
On examination, the baby was very ill with severe cardiac failure. The pulses in the left arm and both femorals were weak to palpation and systolic blood-pressures were 100 mm Hg in the right arm, 68 in the left arm, and 64 in both legs. Digoxin and diuretics were started. At cardiac catheterisation, angiography demonstrated complete interruption of the aortic arch. Flow to the descending aorta was through a patent ductus arteriosus and the left sub-
clavian artery arose from this lower segment. In addition, there was a ventricular septal defect and an atrial defect. The pressures were: right ventricle 100/14 mm Hg, main pulmonary artery 100/55, and descending aorta 55/45. During the procedure bicarbonate was given to correct metabolic acidosis. P.G.EI5 0.11 g/kg/min, was infused directly into the ductus arteriosus via a catheter positioned there from the venous side. Within 10 min, the pressure in the descending aorta rose from 55/45 to 72/46 mm Hg suggesting reopening of the ductus. Simultaneously, the pulmonary-artery pressure fell to 94/50
mm Hg. A cannula was left in the inferior sion continued at 0.03
and p.G.E1 infuthe reduced dose, Despite g/kg/min. the improvement in the general haemodynamic status of the patient was maintained and he began to pass urine. The systolic pressure in his legs remained around 65 mm Hg. However, he developed generalised seizures and eventually entered into status epilepticus. This was attributed to severe hypocalcaemia, and p.G.EI treatment was maintained while the status epilepticus was controlled with anticonvulsants and by correction of the hypocalcaemia. The heemodynamic improvement persisted during p.G.EI treatment, and at the age of 13 days surgical correction under deep hypothermia was scheduled. Unfortunately, the infant developed ventricular fibrillation as his chest was
vena cava
opened and he could not be resuscitated.
At necropsy, the patency of the ductus arteriosus was confirmed along with the interrupted aortic arch and ventricular septal defect.
Although arteriosus is
interruption
the relaxant action of P.G.E, on the ductus striking under hypoxic conditions,4 its use in of the aortic arch has previously been suggested.2
most
Elliott, R. B., Starling, M. B., Neutze, J. M. Lancet, 1975, i, 140. Olley, P M., Coceani, F., Bodach, E. Circulation, 1976, 53, 728 3 Goor, D A, Lillehei, C. W. Congenital Malformations of the Heart, p. 281 New York, 1975. 4 Coceani, F., Olley, P. M. Can. J. Physiol. Pharmac. 1973, 51, 220. 1. 2
I
i
I
*With respect to tumour injection. tFrom Wilcoxon non-parametric rank
i
i
test.
In these tests (see accompanying initiated by intravenous (i.v.)
were
I
table) pulmonary tumours injection of cells from two
syngeneically transplanted tumours in Wistar rats3-methylcholanthrene-induced sarcoma (Mc40A’) and an aminoazodye-induced hepatoma (D23’). Treatment was given by subcutaneous (s.c.) or intrapleural (i.pl.) injection of B.C.G. (Glaxo percutaneous vaccine B.P., 3x 107 viable units/mg moist weight of organisms, representing approximately 20% viability). In the first ten untreated animals survived for 16-23 days, all having to be killed because of extensive pulmonary tumour growth, but a single intrapleural injection of B.C.G. prolonged survival to 24-65 days. Similar results were obtained in two other tests, where the effect of intrapleural B.C.G. significantly prolonged survival, while s.c. injection of the vaccine had a smaller and less consistent effect. These preliminary findings may help to provide a rational basis for treatment of lung tumours by intrapleurally administered B.c.G., the indication being that this route is superior to distant injection. In addition, they provide an experimental model for screening other adjuvants, and for investigating the mechanism of action of intrapleural B.C.G. Previous studies, with subcutaneous tumour growths in rats, have demonstrated that tumour supression by regionally applied B.C.G. depends more upon local activation of host macrophages than upon general immunostimulation,4and further tests are in pro1. 2. 3. 4. 5.
Pimm, M. V., Baldwin, R. W. Int. J. Cancer, 1975, 15, 260. Pimm, M. V., Baldwin, R. W. Br J. Cancer, 1973, 27, 48. Baldwin, R. W., Pimm, M. V. ibid. 1974, 30, 473. Hopper, D. G, Pimm, M. V., Baldwin, R. W. Cancer Immun, 1976, 1, 143. Pimm, M. V., Hopper, D. G. Br. J. Cancer, 1975, 32, 241.
Immunother.
