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LUNG TRANSPLANTATION
209
obstruction
or
fistult, and in
all
early postoperative
examinations.
Lilienfeld 14 and Lilienfeld and Ross 15 have shed light on the absorption of water-soluble contrast media from the alimentary tract which is responsible for the occasional The normal subject excretes coincident pyelogram. about 20% of the ingested contrast medium through his kidneys, but the proportion can be reduced by increasing the concentration in which it is administered and by giving an alkali such as 4 g. of sodium bicarbonate. Absorption is rapid when there is any sinus track or other direct contact between the medium and body-tissues: in 3 patients with bowel fistulas the urinary excretion was nearly doubled. There was a similar increase in patients with obstructive jaundice, the absence of bile in the gut increasing the absorption-rate. The concentration in the bile of dogs which had a biliary fistula after ligation of the common duct was very low-of the order of 1 %. Used with discretion, water-soluble media have an undoubted though limited place in preference to barium sulphate. For general use barium sulphate is still much preferable, on account of its uniformity of behaviour, adherence to the mucosa, and low cost.
another-is
a
different
matter.
The obstacle here is
immunological rejection of the transplanted organ. Hardy et al.23 attempted to suppress the immune response by means of radiomimetic drugs. Control dogs that survived homotransplantation rejected the lung on an average in a week, but, when methotrexate was given, the survival-time in 20 dogs was almost twice as long. When azathioprine (’ Imuran’) or azathioprine and hydrocortisone were used as immunosuppressants, 30 dogs survived for almost a month-four times the length of survival of the controls. But here again, removal of the contralateral normal lung soon after the transplantation caused death of the dogs, though all respiratory activity could be supported for a few days in some. Apparently, then, respiratory capacity can be augmented for a time before a lung homograft is rejected. As with kidney transplants, lung transplants between monozygotic or isogenous persons could conceivably be accepted; but, in the absence of better means of suppressing the immune response, lung transplantation seems to have grave limitations. The immune barrier, as MacPhee and Wright observe, remains in the way.
-
MUSCLE AND ITS DISEASES LUNG TRANSPLANTATION
TRANSPLANTATION of the lung in man has not been In the laboratory the preliminary stages towards some assurance of eventual success have been passed. The first question that had to be answered was whether the lung could continue to function if it was taken out and put back again. In dogs the operation itself (described elsewhere in this issue by Mr. MacPhee and Mr. Wright) has been shown to be feasible.16-21 As to function, Reemtsma et al.,22 in common with other workers, found that ventilation remained almost normal in dogs subjected to left pneumonectomy and immediate replacement of the lung, but that oxygen uptake was impaired, though this subsequently returned to normal. The removed lung can function after being kept at 4°C for two hours, and occasionally even for twenty-four hours, but reimplantation of the lung should’preferably not be delayed for more than a few hours.23 Although dogs can survive reimplantation of a lung for as long as three years, they usually die within a few days if the normal lung on the other side is completely removed soon after. But Nigro et al,24 had some success when they delayed intervention for a few months. They then removed the upper lobe on the normal side, and a month later cauterised the lowerlobe bronchus with silver nitrate. The effect was to put the whole lung on that side out of action, leaving only the reimplanted lung to function. 3 out of 8 dogs so treated survived two to two and a half years after the original operation; 1 gave birth to a litter of 6 normal puppies while living on the reimplanted lung alone. So much for autotransplantation. Homologous transplantation-the implantation of a lung from one dog into
reported.
14. Lilienfeld, R. M. Act. radiol., Stockh. 1959, 51, 251. 15. Lilienfeld, R. M., Ross, C. A. Amer. J. Roentgenol. 1960, 83, 931. 16. Neptune, W. B., Redondo, J., Bailey, C. P. Surg. Forum, 1953, 3, 379. 17. Hardin, C. A., Kettle, F. C. Science, 1954, 119, 97. 18. Hughes, F. A., Kehne, J. H., Fox, J. R. Surgery, 1954, 36, 1101. 19. Lmberg, E. J., Demetriades, A., Armstrong, B. W., Konsuwan, N. J. Amer. med. Ass. 1961, 178, 486. 20. Nigro, S. L., Reimann, A. F., Fry, W. A., Mock, L. F., Adams, W. E. Surg. Forum, 1961, 12, 56. 21. Yeh, T. J., Ellison, I. T., Ellison, R. G. Amer. Rev. resp. Dis. 1962,
86, 791.
22. Reemtsma, K., Rogers, R. E., Lucas, J. F., Schmidt, F. E., J. thorac. cardiovasc. Surg. 1963, 46, 589. 23. Hardy, J. D., Eraslan, S., Dalton, M. L., Jr. ibid. p. 606. 24. Nigro, S. L., Evans, R. H., Benfield, J. R., Gago, O., Adams, W. E. ibid. p. 598.
Davis, F.
H.
W.
A.,
Fry,
INCREASING interest in the anatomy and physiology of skeletal muscle and in the diseases which affect it has been acknowledged by the American Journal of Medicine in a symposium issue published last November; and the seven papers encompass a good deal of present knowledge about structure, function, and diseases of muscle. Price1 describes the ultramicroscopic structure of human skeletal muscle. He shows conclusively that views previously expressed about the structure of the myofibril (based largely on studies of material from the rabbit and other animals 2) also apply to man. Mommaerts3 draws particular attention to the importance of the sarcotubular system in transmission of the electrical impulse from the fibre membrane into the interior of the cell, and confirms the existence of a relaxing factor.4 Apparently the actin and myosin filaments can be induced to contract through the action of adenosine triphosphate, which is in turn produced in the mitochondria by oxidative phosphorylation and in the sarcoplasm by glycolysis; but such contraction can be inhibited by a relaxing factor. Valuable information from neurophysiological studies is described by Johns. The normal membrane potential recorded by inserting a microelectrode into a muscle cell is about 80 mV. This membrane potential can be recorded both in vivo and in vitro. Although this potential depends on the concentration of ions on either side of the fibre membrane, it remains normal in hypokalaemic periodic paralysis during an attack 6; apparently when paralysis occurs, while potassium moves into the cell, there is also a massive influx of water. In the hyperkalsemic type,7 by contrast, there is a slight but significant reduction in
potential. Genetic aspects of muscle diseases are covered by Boyer and Fainer,8 who give reasons for believing in the genetic heterogeneity of the different forms of muscle disease. Whereas a single gene may be involved in all forms of Price, H. M. Amer. J. Med. 1963, 35, 589. Huxley, H. E. J. Biophys. Biochem. Cytol. 1957, 3, 631. Mommaerts, W. F. H. M. Amer. J. Med. 1963, 35, 606. Gergely, J. Ann. N.Y. Acad. Sci. 1959, 81, 490. Johns, R. J. Amer. J. Med. 1963, 35, 611. Shy, G. M., Wanko, T., Rowley, P. T., Engel, A. G. Exp. Neurol. 1961, 3, 53. 7. Creutzfeldt, O. D., Abbott, B. C., Fowler, W. M. Pearson, C. M. Electroenceph. clin. Neurophysiol. 1963, 15, 508. 8. Boyer, S. H., Famer, D. C. Amer. J. Med. 1963, 35, 622. 1. 2. 3. 4. 5. 6.
obstruction
or
fistult, and in
all
early postoperative
examinations.
Lilienfeld 14 and Lilienfeld and Ross 15 have shed light on the absorption of water-soluble contrast media from the alimentary tract which is responsible for the occasional The normal subject excretes coincident pyelogram. about 20% of the ingested contrast medium through his kidneys, but the proportion can be reduced by increasing the concentration in which it is administered and by giving an alkali such as 4 g. of sodium bicarbonate. Absorption is rapid when there is any sinus track or other direct contact between the medium and body-tissues: in 3 patients with bowel fistulas the urinary excretion was nearly doubled. There was a similar increase in patients with obstructive jaundice, the absence of bile in the gut increasing the absorption-rate. The concentration in the bile of dogs which had a biliary fistula after ligation of the common duct was very low-of the order of 1 %. Used with discretion, water-soluble media have an undoubted though limited place in preference to barium sulphate. For general use barium sulphate is still much preferable, on account of its uniformity of behaviour, adherence to the mucosa, and low cost.
another-is
a
different
matter.
The obstacle here is
immunological rejection of the transplanted organ. Hardy et al.23 attempted to suppress the immune response by means of radiomimetic drugs. Control dogs that survived homotransplantation rejected the lung on an average in a week, but, when methotrexate was given, the survival-time in 20 dogs was almost twice as long. When azathioprine (’ Imuran’) or azathioprine and hydrocortisone were used as immunosuppressants, 30 dogs survived for almost a month-four times the length of survival of the controls. But here again, removal of the contralateral normal lung soon after the transplantation caused death of the dogs, though all respiratory activity could be supported for a few days in some. Apparently, then, respiratory capacity can be augmented for a time before a lung homograft is rejected. As with kidney transplants, lung transplants between monozygotic or isogenous persons could conceivably be accepted; but, in the absence of better means of suppressing the immune response, lung transplantation seems to have grave limitations. The immune barrier, as MacPhee and Wright observe, remains in the way.
-
MUSCLE AND ITS DISEASES LUNG TRANSPLANTATION
TRANSPLANTATION of the lung in man has not been In the laboratory the preliminary stages towards some assurance of eventual success have been passed. The first question that had to be answered was whether the lung could continue to function if it was taken out and put back again. In dogs the operation itself (described elsewhere in this issue by Mr. MacPhee and Mr. Wright) has been shown to be feasible.16-21 As to function, Reemtsma et al.,22 in common with other workers, found that ventilation remained almost normal in dogs subjected to left pneumonectomy and immediate replacement of the lung, but that oxygen uptake was impaired, though this subsequently returned to normal. The removed lung can function after being kept at 4°C for two hours, and occasionally even for twenty-four hours, but reimplantation of the lung should’preferably not be delayed for more than a few hours.23 Although dogs can survive reimplantation of a lung for as long as three years, they usually die within a few days if the normal lung on the other side is completely removed soon after. But Nigro et al,24 had some success when they delayed intervention for a few months. They then removed the upper lobe on the normal side, and a month later cauterised the lowerlobe bronchus with silver nitrate. The effect was to put the whole lung on that side out of action, leaving only the reimplanted lung to function. 3 out of 8 dogs so treated survived two to two and a half years after the original operation; 1 gave birth to a litter of 6 normal puppies while living on the reimplanted lung alone. So much for autotransplantation. Homologous transplantation-the implantation of a lung from one dog into
reported.
14. Lilienfeld, R. M. Act. radiol., Stockh. 1959, 51, 251. 15. Lilienfeld, R. M., Ross, C. A. Amer. J. Roentgenol. 1960, 83, 931. 16. Neptune, W. B., Redondo, J., Bailey, C. P. Surg. Forum, 1953, 3, 379. 17. Hardin, C. A., Kettle, F. C. Science, 1954, 119, 97. 18. Hughes, F. A., Kehne, J. H., Fox, J. R. Surgery, 1954, 36, 1101. 19. Lmberg, E. J., Demetriades, A., Armstrong, B. W., Konsuwan, N. J. Amer. med. Ass. 1961, 178, 486. 20. Nigro, S. L., Reimann, A. F., Fry, W. A., Mock, L. F., Adams, W. E. Surg. Forum, 1961, 12, 56. 21. Yeh, T. J., Ellison, I. T., Ellison, R. G. Amer. Rev. resp. Dis. 1962,
86, 791.
22. Reemtsma, K., Rogers, R. E., Lucas, J. F., Schmidt, F. E., J. thorac. cardiovasc. Surg. 1963, 46, 589. 23. Hardy, J. D., Eraslan, S., Dalton, M. L., Jr. ibid. p. 606. 24. Nigro, S. L., Evans, R. H., Benfield, J. R., Gago, O., Adams, W. E. ibid. p. 598.
Davis, F.
H.
W.
A.,
Fry,
INCREASING interest in the anatomy and physiology of skeletal muscle and in the diseases which affect it has been acknowledged by the American Journal of Medicine in a symposium issue published last November; and the seven papers encompass a good deal of present knowledge about structure, function, and diseases of muscle. Price1 describes the ultramicroscopic structure of human skeletal muscle. He shows conclusively that views previously expressed about the structure of the myofibril (based largely on studies of material from the rabbit and other animals 2) also apply to man. Mommaerts3 draws particular attention to the importance of the sarcotubular system in transmission of the electrical impulse from the fibre membrane into the interior of the cell, and confirms the existence of a relaxing factor.4 Apparently the actin and myosin filaments can be induced to contract through the action of adenosine triphosphate, which is in turn produced in the mitochondria by oxidative phosphorylation and in the sarcoplasm by glycolysis; but such contraction can be inhibited by a relaxing factor. Valuable information from neurophysiological studies is described by Johns. The normal membrane potential recorded by inserting a microelectrode into a muscle cell is about 80 mV. This membrane potential can be recorded both in vivo and in vitro. Although this potential depends on the concentration of ions on either side of the fibre membrane, it remains normal in hypokalaemic periodic paralysis during an attack 6; apparently when paralysis occurs, while potassium moves into the cell, there is also a massive influx of water. In the hyperkalsemic type,7 by contrast, there is a slight but significant reduction in
potential. Genetic aspects of muscle diseases are covered by Boyer and Fainer,8 who give reasons for believing in the genetic heterogeneity of the different forms of muscle disease. Whereas a single gene may be involved in all forms of Price, H. M. Amer. J. Med. 1963, 35, 589. Huxley, H. E. J. Biophys. Biochem. Cytol. 1957, 3, 631. Mommaerts, W. F. H. M. Amer. J. Med. 1963, 35, 606. Gergely, J. Ann. N.Y. Acad. Sci. 1959, 81, 490. Johns, R. J. Amer. J. Med. 1963, 35, 611. Shy, G. M., Wanko, T., Rowley, P. T., Engel, A. G. Exp. Neurol. 1961, 3, 53. 7. Creutzfeldt, O. D., Abbott, B. C., Fowler, W. M. Pearson, C. M. Electroenceph. clin. Neurophysiol. 1963, 15, 508. 8. Boyer, S. H., Famer, D. C. Amer. J. Med. 1963, 35, 622. 1. 2. 3. 4. 5. 6.