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JET INJECTION OF JOINTS
1200 Los Angeles have lately reviewed the subject of virus diseases in pregnancy as they afFect the child. Abortion may result from maternal infection with influenza or poliomyelitis, but congenital anomalies attributed to a disease other than rubella are mentioned in only one of the reports to which Adams et al. refer, and in that one5
poliomyelitis
was
thought
to be
responsible.
Adams et al. infected mice with influenza virus intra-
nasally just before breeding. Death or abnormality of the embryos was not significantly more common than in controls ; but technical points concerning the dose and time of administration of virus need further investigation. On the other hand, Adams et al. found that chick embryos, infected with influenza at 48 hours of age, became deformed and died. Prior inoculation of .antiserum the protected embryos, and antiserum inoculated up to 5 hours after the virus gave partial protection. These results with chick embryos may be compared with those of Henle et allwho infected 8-day chick embryos with ultraviolet-irradiated influenza virus and noted stunting of growth of embryo and a,llantois during the succeeding 7 days. Death in that period was unusual, and the experiments were not continued till hatching. Homologous antiserum gave protection when given at the same time as the virus, but antiserum given even as soon as 1 minute after the virus did not prevent interference with the growth of the embryo.
These experiments throw no light on what influenza in the mother may do to a human embryo. The experiments with mice were inconclusive, and the chick embryos, though undoubtedly damaged by the virus, were infected in a way which exposed their cells to direct contact with an inoculum of virus that was very large compared with the dose that could cross a human placenta. Furthermore, in Henle’s experiments the embryos were damaged by virus whose infectivity had been destroyed by ultraviolet light. Gregghas summed up the situation by saying that though congenital abnormality has been attributed to maternal infection with mumps, influenza, smallpox, chickenpox, poliomyelitis, and infective hepatitis there is no regular of anomalies as there is in the rubella syndrome.
pattern
A PIONEER IN NEUROLOGY
THE guarantors of Brain have published 8 a selection of the papers of Sir Gordon Holmes as a tribute to this great neurologist on his 80th birthday. Though it has not been possible to produce as wide a selection as was done for Hughlings Jackson 9 and Sherrington, 10 there is quite enough to show how much Holmes has contributed to fundamental knowledge in neurology. His pioneer work on the cerebellum is represented by his paper of 1908 on the connection of the inferior olives with the cerebellum in man, by the paper on a familial degeneration of the cerebellum, by the greater part of his paper with Dr. Grainger Stewart which, in 1904, established the clinical signs of intracerebellar and extracerebellar tumours, and by the Croonian lectures of 1922 based largely on his study of gunshot wounds of the cerebellum. The other writings which have been reprinted are concerned with the cortical representation of vision and with visual orientation and attention, including the two classical papers of 1916 and 1918 in which Holmes established the point-to-point representation of the 5. Aycock, W. L., Ingalls, T. H. Amer. J. med. Sci. 1946, 212, 366. 6. Henle, W., Henle, G., Kirber, M. W. Ibid, 1947, 214, 529. 7. Gregg, N. M. Trans. Amer. Acad. Ophthal. Oto-laryng. 1956, 60,
199. 8. Selected Papers of Sir Gordon Holmes. Compiled and edited by Sir Francis Walshe, F.R.C.P., F.R.S. London : Macmillan. 1956. Pp. 264. 20s. 9. Selected Works of John Hughlings Jackson. London. 2 vols., 1931 and 1932. 10. Selected Writings of Sir Charles Sherrington. London, 1939.
retina, in the occipital cortex. Many neurologists will miss the (toulstonian lectures of 1914 on the spinal injuries of warfare, which contained much meticulous observation, and the Horsley lecture of 1938 on the cerebral integration of ocular movements. The other major omission is the paper with Sir Henry Head on sensory disturbances from cerebral lesions ; this has. in fact, been reprinted 11 since it originally appeared, but in a volume which is not now easily obtainable. As Sir Francis Walshe points out in his preface, all this fundamental work, and much more that is given in the bibliography, was carried out in the " spare time" of a clinician busily occupied in hospital and private practice, and much of it, particularly on the cortical representation of vision, while Holmes was on active service during the 1914-18 war. This colledion will bring special pleasure to all the house-physicians and clinical clerks who have worked at the National Hospital -with this celebrated teacher of
lleurologv. JET INJECTION OF JOINTS INTRA-ARTIcuLAR injections of hydrocortisone acetate now have an accepted place in the treatment of rheuma. toid arthritis, especially in patients who have only a few Ziff et al.12 have lately recorded troublesome joints. results with a "hypospray" jet injector which, they believe, can usefully replace the conventional syringe in this type of treatment. This ingenious device 13 11 was designed to introduce substances under pressure either subcutaneously or intramuscularly without using a needle. The material to be injected is contained in small metal cartridges, hermetically sealed in a sterile aluminium container, and it is forced through the skin as a fine jet by a spring-activated plunger. To ensure adequate penetration of periarticular structures, a special injector, about 18% stronger than the standard instrument, was developed. Only the nozzle of the injector and the skin need be sterilised. In preliminary experiments a solution of a dye or a suspension of hydrocortisone acetate was injected into joints. The proportion of injected material which could be recovered by aspiration of the joint contents was as high as 60% for the dye, but much smaller for the hydrocortisone-probably because much of it remained in the synovial membrane or periarticular tissues. Jet injection of a radio-opaque medium confirmed that the material was deposited in periarticular structures as well as within the joint cavity. Ziff and his colleagues suggest that the action of the hydrocortisone which actually enters the joint may be supplemented by the rest of the dose which is deposited around the joint. Clinically the response seems to have been much the same as that produced by ordinary syringe-and-needle injection. The smaller joints responded best and the method seemed most suitable for the digital joints, in which local treatment with hydrocortisone is often worth while and is perhaps used less often than elsewhere. ; Nearly all patients felt a sudden sharp or burning sensation at the moment of injection, and discomfort for several minutes afterwards, especially when small joints were treated. ; but most preferred the hypospray to injection with a needle. The only common reaction was slight ecchymosis ; one patient bled from a small artery, and another had a small but persistent area of anaesthesia distal to the site of injection. The method has the disadvantage that it does not allow fluid to be withdrawn for or therapeutic purposes. Although attractively simple and quick, and apparently safe in
diagnostic
11. Head, H. Studies in Neurology. London, 1920. 12. Ziff, M., Contreras, V., Schmid, F. R. Ann. rheum. Dis. 1956, 15, 227. 13. Figge, F. H. J., Barnett, D. J. Amer. Pract. 1948, 3, 197. 14. Hughes, J. G., Jordan, R. G., Hill, F. S. Sth. med. J. 1949, 42, 296.
1201 "
originators, jet " injection is unlikely to compete seriously with an accurately directed needle until bigger trials have been undertaken. the hands of its
CARDIAC ARREST
THE importance of early cardiac massage through the chest in the treatment of cardiac arrest due to ventricular fibrillation or standstillhas again been illustrated by --Nfilstein.2 But cardiac massage carries a considerable risk of traumatic damage, particularly in the hands of those not practised in chest surgery ; and it is tiring for the operator. An ingenious alternative method named "pneumomassage," involving the rhythmic insufflation of gas into the pericardial cavity, has been devised by Bencini and Parola3 in Milan for accomplishing cardiac massage with less trauma. A special cannula, introduced through a small hole in the pericardium, is held in place by a flange on each side. Air, or oxygen, is rhythmically blown in by a rubber bulb or an oxygen cylinder, preferably with a manometer inthe circuit. Bencini and Parola used a pressure up to 160 mm. Hg in dogs, after finding that the pericardium would stand pressures at least to 350 mm. Hg. The breaking-point in nine human cadavers varied from 710 to 1125 mm. Hg. The method seemed very efficient in induced ventricular fibrillation in dogs : it produced a femoral pulse and a systolic pressure of about 100 mm. Hg ; and, after 10-60 minutes, electric defibrillation was always achieved with the first shock. Pressure measurements from the right auricle and jugular vein showed little venous reflux. The method has yet to be applied in man, and even if it is successful it may have only a limited practical use. For instance, in patients undergoing cardiac surgery the pericardium is unlikely to be intact. And in surgery outside the thorax time is all-important, and manual massage will usually be quicker. Pneumomassage may be valuable when treatment must be continued and the pericardium has not been opened ; and it might prove useful for those unaccustomed to thoracic surgery if a simple and rapid method of introducing the cannula into the pericardium could be devised. Early cardiac massage (followed if necessary by defibrillation with the electrodes placed on the heart) is a welltried and effective treatment for ventricular fibrillation or standstill. But its use is restricted because a physician, and even a general surgeon, may hesitate to do an immediate thoracotomy. Intracardiac drugs are usually ineffective and may be dangerous.4 It has been found recently that an electric shock applied through the intact chest wall may restore normal ventricular action if it can be started soon enough while the myocardium is still well oxygenated. The difficulty is that 3 to 5 minutes after the onset of ventricular fibrillation or standstill the myocardium becomes unresponsive, and (at normal temperatures) irreversible changes take place °in the central nervous system. Moreover, it may be hard to differentiate between fibrillation and standstill, and that is important because fibrillation calls for a much greater electrical stimulus than standstill. Differentiation is easy with a continuous electrocardiogram, particularly when it is displayed on a cathode-ray tube ; but except during cardiac investigations and surgery, this information will seldom be readily obtainable. It is probable that standstill is more usual, except as a complication of
operations involving handling of the heart ; but figures bearing on this subject are misleading unless based on direct observation of the heart through the opened pericardium or on a continuous electrocardiogram. 1. Lancet, 1954, ii, 1217. 2. Milstein, B. B. Ann. R. Coll. Surg. 1956, 19, 69. 3. Bencini, A., Parola, P. L. Surgery, 1956, 39, 375. 4. McMillan, I. K. R., Cockett, F. B., Styles, P. Thorax, 1952, 7, 205.
External electric defibrillation through the chest wall requires such large currents that it has been thought impracticable,5 but Zoll et al. have not been deterred and they now report the successful termination of 11 episodes of ventricular fibrillation in this way. Between 240 and 720 volts, giving up to 15 amps, were used in shocks lasting 0-15 second applied over the precordium. Of four patients three eventually died, but one survived several episodes of defibrillation and made a complete recovery. In the successful case the shock was applied within 4 minutes of the onset of fibrillation ; in the patients who died there was a delay of at least 7 minutes. Surprisingly, no mention is made of burning of the skin, which seems likely with such enormous currents. The method must also be hazardous for the operator.
External electric stimulation for ventricular standstill 78 is much easier and safer since relatively small voltages and currents are required. Again the main difficulty is that treatment must be started very rapidly ; and probably for this reason the best results have been reported in Stokes-Adams attacks, whose repetitive nature allows the instrument to be set up beforehand. In this issue Dr. Leatham and his colleagues discuss a simple automatic apparatus for external stimulation. A warning device brings the instrument automatically into action if no Q R. s is received from a continuous electrocardiogram, thus avoiding any dangerous delay. For emergency use an ordinary high-tension battery, condenser, and morse key were sufficient. If its value is confirmed by further experience, this simple apparatus could at least be available, to meet the danger of a recurrence, beside the bed of any patient who has frequent Stokes-Adams attacks, or who has returned to ’the ward after cardiac massage for standstill. ELUSIVE VIRUS THREE months ago9 we drew attention to the report by Rightsel and his colleagues at Parke Davis Research Laboratories, Detroit, of the isolation, from acute sera and stools of infective hepatitis, of agents with a cytopathic action on cultures of a strain of cells known as Detroit-6. No other laboratory has succeeded in confirming these results, but the essential requirements for satisfactory culture are fraught with difficulties. At the meeting we report on p. 1207 McLean, one of Rightsel’s colleagues, stated that the cells remained susceptible to the agents only if they were cultivated in human serum ; but, on the other hand, the agent or agents being investigated may be present in the serum of an apparently normal human, and there is no proven method of inactivating hepatitis virus which will not spoil the serum’s growth-promoting properties. The difficulties of maintaining clean " lines of cells are obvious. McLean and his colleagues reported that convalescent sera were better able to neutralise the action of the agents than acute-stage non-infective sera ; but the agent had also been isolated from some early convalescent sera. After as many as 12 passages, the agents still had a titre of only 10-1 and they had not been capable of producing illness or antibodies in the several species of laboratory animals which had been inoculated. In the discussion at Detroit Sternberg stated that Detroit-6 cells, which were originally derived from the bone-marrow of a patient with carcinoma of the lung, may undergo cyclical degeneration. The Detroit workers are trying to adapt their agents to other lines of cells, and most workers who are still searching for susceptible cells consider that this is essential. "
Wiggers, C. J. Amer. Heart J. 1940, 20, 413. Zoll, P. M., Linenthal, A. J., Gibson, W., Paul, M. H., Norman, L. R. New Engl. J. Med. 1956, 254, 727. 7. Zoll, P. M., Linenthal, A. J., Norman, L. R. Circulation, 1954, 9, 482. 8. Zoll, P. M., Linenthal, A. J., Norman, L. R., Paul, M. H., Gibson, W. Arch. intern. Med. 1955, 96, 639. 9. Lancet, Sept. 1, 1956, p. 449. 5. 6.
poliomyelitis
was
thought
to be
responsible.
Adams et al. infected mice with influenza virus intra-
nasally just before breeding. Death or abnormality of the embryos was not significantly more common than in controls ; but technical points concerning the dose and time of administration of virus need further investigation. On the other hand, Adams et al. found that chick embryos, infected with influenza at 48 hours of age, became deformed and died. Prior inoculation of .antiserum the protected embryos, and antiserum inoculated up to 5 hours after the virus gave partial protection. These results with chick embryos may be compared with those of Henle et allwho infected 8-day chick embryos with ultraviolet-irradiated influenza virus and noted stunting of growth of embryo and a,llantois during the succeeding 7 days. Death in that period was unusual, and the experiments were not continued till hatching. Homologous antiserum gave protection when given at the same time as the virus, but antiserum given even as soon as 1 minute after the virus did not prevent interference with the growth of the embryo.
These experiments throw no light on what influenza in the mother may do to a human embryo. The experiments with mice were inconclusive, and the chick embryos, though undoubtedly damaged by the virus, were infected in a way which exposed their cells to direct contact with an inoculum of virus that was very large compared with the dose that could cross a human placenta. Furthermore, in Henle’s experiments the embryos were damaged by virus whose infectivity had been destroyed by ultraviolet light. Gregghas summed up the situation by saying that though congenital abnormality has been attributed to maternal infection with mumps, influenza, smallpox, chickenpox, poliomyelitis, and infective hepatitis there is no regular of anomalies as there is in the rubella syndrome.
pattern
A PIONEER IN NEUROLOGY
THE guarantors of Brain have published 8 a selection of the papers of Sir Gordon Holmes as a tribute to this great neurologist on his 80th birthday. Though it has not been possible to produce as wide a selection as was done for Hughlings Jackson 9 and Sherrington, 10 there is quite enough to show how much Holmes has contributed to fundamental knowledge in neurology. His pioneer work on the cerebellum is represented by his paper of 1908 on the connection of the inferior olives with the cerebellum in man, by the paper on a familial degeneration of the cerebellum, by the greater part of his paper with Dr. Grainger Stewart which, in 1904, established the clinical signs of intracerebellar and extracerebellar tumours, and by the Croonian lectures of 1922 based largely on his study of gunshot wounds of the cerebellum. The other writings which have been reprinted are concerned with the cortical representation of vision and with visual orientation and attention, including the two classical papers of 1916 and 1918 in which Holmes established the point-to-point representation of the 5. Aycock, W. L., Ingalls, T. H. Amer. J. med. Sci. 1946, 212, 366. 6. Henle, W., Henle, G., Kirber, M. W. Ibid, 1947, 214, 529. 7. Gregg, N. M. Trans. Amer. Acad. Ophthal. Oto-laryng. 1956, 60,
199. 8. Selected Papers of Sir Gordon Holmes. Compiled and edited by Sir Francis Walshe, F.R.C.P., F.R.S. London : Macmillan. 1956. Pp. 264. 20s. 9. Selected Works of John Hughlings Jackson. London. 2 vols., 1931 and 1932. 10. Selected Writings of Sir Charles Sherrington. London, 1939.
retina, in the occipital cortex. Many neurologists will miss the (toulstonian lectures of 1914 on the spinal injuries of warfare, which contained much meticulous observation, and the Horsley lecture of 1938 on the cerebral integration of ocular movements. The other major omission is the paper with Sir Henry Head on sensory disturbances from cerebral lesions ; this has. in fact, been reprinted 11 since it originally appeared, but in a volume which is not now easily obtainable. As Sir Francis Walshe points out in his preface, all this fundamental work, and much more that is given in the bibliography, was carried out in the " spare time" of a clinician busily occupied in hospital and private practice, and much of it, particularly on the cortical representation of vision, while Holmes was on active service during the 1914-18 war. This colledion will bring special pleasure to all the house-physicians and clinical clerks who have worked at the National Hospital -with this celebrated teacher of
lleurologv. JET INJECTION OF JOINTS INTRA-ARTIcuLAR injections of hydrocortisone acetate now have an accepted place in the treatment of rheuma. toid arthritis, especially in patients who have only a few Ziff et al.12 have lately recorded troublesome joints. results with a "hypospray" jet injector which, they believe, can usefully replace the conventional syringe in this type of treatment. This ingenious device 13 11 was designed to introduce substances under pressure either subcutaneously or intramuscularly without using a needle. The material to be injected is contained in small metal cartridges, hermetically sealed in a sterile aluminium container, and it is forced through the skin as a fine jet by a spring-activated plunger. To ensure adequate penetration of periarticular structures, a special injector, about 18% stronger than the standard instrument, was developed. Only the nozzle of the injector and the skin need be sterilised. In preliminary experiments a solution of a dye or a suspension of hydrocortisone acetate was injected into joints. The proportion of injected material which could be recovered by aspiration of the joint contents was as high as 60% for the dye, but much smaller for the hydrocortisone-probably because much of it remained in the synovial membrane or periarticular tissues. Jet injection of a radio-opaque medium confirmed that the material was deposited in periarticular structures as well as within the joint cavity. Ziff and his colleagues suggest that the action of the hydrocortisone which actually enters the joint may be supplemented by the rest of the dose which is deposited around the joint. Clinically the response seems to have been much the same as that produced by ordinary syringe-and-needle injection. The smaller joints responded best and the method seemed most suitable for the digital joints, in which local treatment with hydrocortisone is often worth while and is perhaps used less often than elsewhere. ; Nearly all patients felt a sudden sharp or burning sensation at the moment of injection, and discomfort for several minutes afterwards, especially when small joints were treated. ; but most preferred the hypospray to injection with a needle. The only common reaction was slight ecchymosis ; one patient bled from a small artery, and another had a small but persistent area of anaesthesia distal to the site of injection. The method has the disadvantage that it does not allow fluid to be withdrawn for or therapeutic purposes. Although attractively simple and quick, and apparently safe in
diagnostic
11. Head, H. Studies in Neurology. London, 1920. 12. Ziff, M., Contreras, V., Schmid, F. R. Ann. rheum. Dis. 1956, 15, 227. 13. Figge, F. H. J., Barnett, D. J. Amer. Pract. 1948, 3, 197. 14. Hughes, J. G., Jordan, R. G., Hill, F. S. Sth. med. J. 1949, 42, 296.
1201 "
originators, jet " injection is unlikely to compete seriously with an accurately directed needle until bigger trials have been undertaken. the hands of its
CARDIAC ARREST
THE importance of early cardiac massage through the chest in the treatment of cardiac arrest due to ventricular fibrillation or standstillhas again been illustrated by --Nfilstein.2 But cardiac massage carries a considerable risk of traumatic damage, particularly in the hands of those not practised in chest surgery ; and it is tiring for the operator. An ingenious alternative method named "pneumomassage," involving the rhythmic insufflation of gas into the pericardial cavity, has been devised by Bencini and Parola3 in Milan for accomplishing cardiac massage with less trauma. A special cannula, introduced through a small hole in the pericardium, is held in place by a flange on each side. Air, or oxygen, is rhythmically blown in by a rubber bulb or an oxygen cylinder, preferably with a manometer inthe circuit. Bencini and Parola used a pressure up to 160 mm. Hg in dogs, after finding that the pericardium would stand pressures at least to 350 mm. Hg. The breaking-point in nine human cadavers varied from 710 to 1125 mm. Hg. The method seemed very efficient in induced ventricular fibrillation in dogs : it produced a femoral pulse and a systolic pressure of about 100 mm. Hg ; and, after 10-60 minutes, electric defibrillation was always achieved with the first shock. Pressure measurements from the right auricle and jugular vein showed little venous reflux. The method has yet to be applied in man, and even if it is successful it may have only a limited practical use. For instance, in patients undergoing cardiac surgery the pericardium is unlikely to be intact. And in surgery outside the thorax time is all-important, and manual massage will usually be quicker. Pneumomassage may be valuable when treatment must be continued and the pericardium has not been opened ; and it might prove useful for those unaccustomed to thoracic surgery if a simple and rapid method of introducing the cannula into the pericardium could be devised. Early cardiac massage (followed if necessary by defibrillation with the electrodes placed on the heart) is a welltried and effective treatment for ventricular fibrillation or standstill. But its use is restricted because a physician, and even a general surgeon, may hesitate to do an immediate thoracotomy. Intracardiac drugs are usually ineffective and may be dangerous.4 It has been found recently that an electric shock applied through the intact chest wall may restore normal ventricular action if it can be started soon enough while the myocardium is still well oxygenated. The difficulty is that 3 to 5 minutes after the onset of ventricular fibrillation or standstill the myocardium becomes unresponsive, and (at normal temperatures) irreversible changes take place °in the central nervous system. Moreover, it may be hard to differentiate between fibrillation and standstill, and that is important because fibrillation calls for a much greater electrical stimulus than standstill. Differentiation is easy with a continuous electrocardiogram, particularly when it is displayed on a cathode-ray tube ; but except during cardiac investigations and surgery, this information will seldom be readily obtainable. It is probable that standstill is more usual, except as a complication of
operations involving handling of the heart ; but figures bearing on this subject are misleading unless based on direct observation of the heart through the opened pericardium or on a continuous electrocardiogram. 1. Lancet, 1954, ii, 1217. 2. Milstein, B. B. Ann. R. Coll. Surg. 1956, 19, 69. 3. Bencini, A., Parola, P. L. Surgery, 1956, 39, 375. 4. McMillan, I. K. R., Cockett, F. B., Styles, P. Thorax, 1952, 7, 205.
External electric defibrillation through the chest wall requires such large currents that it has been thought impracticable,5 but Zoll et al. have not been deterred and they now report the successful termination of 11 episodes of ventricular fibrillation in this way. Between 240 and 720 volts, giving up to 15 amps, were used in shocks lasting 0-15 second applied over the precordium. Of four patients three eventually died, but one survived several episodes of defibrillation and made a complete recovery. In the successful case the shock was applied within 4 minutes of the onset of fibrillation ; in the patients who died there was a delay of at least 7 minutes. Surprisingly, no mention is made of burning of the skin, which seems likely with such enormous currents. The method must also be hazardous for the operator.
External electric stimulation for ventricular standstill 78 is much easier and safer since relatively small voltages and currents are required. Again the main difficulty is that treatment must be started very rapidly ; and probably for this reason the best results have been reported in Stokes-Adams attacks, whose repetitive nature allows the instrument to be set up beforehand. In this issue Dr. Leatham and his colleagues discuss a simple automatic apparatus for external stimulation. A warning device brings the instrument automatically into action if no Q R. s is received from a continuous electrocardiogram, thus avoiding any dangerous delay. For emergency use an ordinary high-tension battery, condenser, and morse key were sufficient. If its value is confirmed by further experience, this simple apparatus could at least be available, to meet the danger of a recurrence, beside the bed of any patient who has frequent Stokes-Adams attacks, or who has returned to ’the ward after cardiac massage for standstill. ELUSIVE VIRUS THREE months ago9 we drew attention to the report by Rightsel and his colleagues at Parke Davis Research Laboratories, Detroit, of the isolation, from acute sera and stools of infective hepatitis, of agents with a cytopathic action on cultures of a strain of cells known as Detroit-6. No other laboratory has succeeded in confirming these results, but the essential requirements for satisfactory culture are fraught with difficulties. At the meeting we report on p. 1207 McLean, one of Rightsel’s colleagues, stated that the cells remained susceptible to the agents only if they were cultivated in human serum ; but, on the other hand, the agent or agents being investigated may be present in the serum of an apparently normal human, and there is no proven method of inactivating hepatitis virus which will not spoil the serum’s growth-promoting properties. The difficulties of maintaining clean " lines of cells are obvious. McLean and his colleagues reported that convalescent sera were better able to neutralise the action of the agents than acute-stage non-infective sera ; but the agent had also been isolated from some early convalescent sera. After as many as 12 passages, the agents still had a titre of only 10-1 and they had not been capable of producing illness or antibodies in the several species of laboratory animals which had been inoculated. In the discussion at Detroit Sternberg stated that Detroit-6 cells, which were originally derived from the bone-marrow of a patient with carcinoma of the lung, may undergo cyclical degeneration. The Detroit workers are trying to adapt their agents to other lines of cells, and most workers who are still searching for susceptible cells consider that this is essential. "
Wiggers, C. J. Amer. Heart J. 1940, 20, 413. Zoll, P. M., Linenthal, A. J., Gibson, W., Paul, M. H., Norman, L. R. New Engl. J. Med. 1956, 254, 727. 7. Zoll, P. M., Linenthal, A. J., Norman, L. R. Circulation, 1954, 9, 482. 8. Zoll, P. M., Linenthal, A. J., Norman, L. R., Paul, M. H., Gibson, W. Arch. intern. Med. 1955, 96, 639. 9. Lancet, Sept. 1, 1956, p. 449. 5. 6.