endocrine transplantation

1
180 procedure than agglutination. An advantage is that other heterogenetic antibodies do not interfere with the reaction. By any method of serological diagnosis, a rising titre is more significant than an isolated reading. Titres can vary widely with slight alterations in technique ; but a sheep-cell-agglutinin titre of over 1 in 30,15 and a haemo- lysin titre to ox cells of over 1 in 40,21 are diagnostic in most cases. 22. Murray, J. E., Merrill, J. P., Harrison, J. H. Surgical Forum. Chicago, 1956 ; vol. 6, p. 432. 23. Dempster, W. J. Brit. med. J. 1951, ii, 1041. 24. Loeb, L. The Biological Brain of Individuality. Springfield, Ill., 1945. 25. Medawar, P. B. J. Anat., Lond. 1944, 78, 176. 26. Billingham, R. E., Krohn, P. L., Medawar, P. B. Brit. med. J. 1951, ii, 1049. 27. Halsted, W. S. J. exp. Med. 1909, 11, 175. 28. Turner, C. D. Anat. Rec. 1939, 73, 145. 29. Woodruff, M. F. A., Woodruff, H. G. Phil. Trans. B. 1950, 234, 559. 30. Broster, L. R., Gardiner-Hill, H. Brit. med. J. 1946, ii, 570. 31. Bland, W. H., Chesson, A. L., Crow, J. B. N. C. med. J. 1950, 11, 501. ENDOCRINE TRANSPLANTATION IT is well known that homotransplants, except oj cornea, cartilage, and blood-vessels, do not survive in man unless the donor and recipient are identical twins. Even between identical twins very few successful trans- plants of whole organs have been performed-one was a kidney transplantation reported last year by Murray et al.22 Dempster 23 pointed out that homotransplants could survive in the lower orders of animal life, but that they became increasingly unsuccessful as the phylo- genetic scale was ascended. Discussing the reasons for the disintegration of transplanted tissues and organs, he cited Loeb’s 24 belief in the importance of the local cellular reaction, but inclined to the view that it was due to an actively acquired immunity reaction on the part of the host. This hypothesis is strongly supported by the work of Medawar,25 who showed that in rabbits second-crop homotransplants of skin from the same donor to the same recipient disintegrated more rapidly than the first crop. He afterwards found that the local application of cortisone to skin-grafts in rabbits prolongs the survival.26 The consistent failure of homotransplants to survive in man has not deterred investigators in this field, and it is not surprising that the transplantation of endocrine glands should have received particular attention. As they are relatively independent of a nerve-supply for their proper functioning, and discharge their secretions directly into the circulation, their transplantation presents no difficult technical problems. Ever since 1909, belief in the ultimate, feasibility of such a pro- cedure has been encouraged by Halsted’s so-called law 27 which states, on very limited evidence, that the trans- plantation of an endocrine gland is more likely to be successful if there exists in the host a deficiency of its particular secretion. This " law " is supported to some extent by the work of Turner,28 and has been explained by Woodruff and Woodruff 29 on the ground that a high circulating level of the appropriate trophic hormone from the pituitary promotes the survival of transplanted endocrine tissue. Halsted’s original observations were, however, based on the transplantation of parathyroids, which are believed not to be the targets of any pituitary hormone. There is as yet no convincing evidence of permanent survival of transplanted endocrine glands in man although therapeutic activity has undeniably been observed for limited periods-for example, in the case of Addison’s disease which Broster and Grardiner-Hill so claimed to have cured by adrenal transplantation, Bland et al.31 claimed the cure of a case of postoperative hypopara- thyroidism by the implantation into the rectus muscle of parathyroid tissue from a 29-year-old man who had just died, but their report covered only four months’ follow-up. y It has been suggested that fcetal tissue, being le, _ antigenic than fully differentiated tissue, would be less liable to destruction by an immune reaction in the host. Dempster 23 is pessimistic about this line of research, but astonishing results have been claimed by Kadyseva of the Jaroslav Medical Institute who has implantel] pituitary glands from 4-5-month-old fcetuses into three pituitary dwarfs, all of whom are said to have responded by substantial acceleration of growth. Kooreman and Gaillard 33 cultivated foetal parathyroid tissue in media to which increasing amounts of serum from the prospective recipient had been added in the hope of " acclimatising " the tissue to its future environ. ment. They reported 42 grafts in 29 hypoparathyroiu patients, in 21 of whom the result had been observed for at least a year. The grafts were apparently entirely successful in 7 of these patients, all below the age of 3h, This lead has now been followed by Escamilla et al.,34 who have applied the method to 14 transplants in il cases of surgical hypoparathyroidism. 6 of these trans- plants were taken from the parathyroids of infants who were stillborn or who died shortly after birth, and 8 were obtained from parathyroid adenomas removed at opera. tion. The parathyroid tissue was grown in a basic salt solution in the presence of increasing concentrations of recipient serum, and implantation was carried out after about two weeks of tissue-culture. The implants wen made into pockets in the sheath of the axillary vein, the number of fragments implanted varying from 13 to 80, The results were on the whole disappointing. In onr case symptoms of hypoparathyroidism had not returned after nineteen months, but unfortunately the diagnosis was not confirmed biochemically before the implantation, In a second patient convincing biochemical improvement was obtained -for about a year, and partial relief ha continued for thirteen months after a second implant. Transient improvement lasting for one to six weeks was seen in 6 cases, and no improvement whatever in the remaining 3. It cannot be said that this latest excursion into the difficult but ever-tempting province of endocrine trans. plantation offers much more hope of useful therapeutic results than have earlier experiments in this direction, But the small measure of success which Escamilla and his colleagues have achieved will no doubt encourage other workers in this field. 32. Kadyseva, N. M. Probl. Endokr. Gormonoter. 1956, 2, 90. 33. Kooreman, P. J., Gaillard, P. J. Arch. chir. neerland. 1950, 2, 326. 34. Escamilla, R. F., Kempe, C. H., Crane, J., Goldman, L., Gordan. G. S. Ann. intern. Med. 1957, 46, 649. DISABILITY TODAY it is increasingly realised that, when we have failed to prevent crippling, our duty is not merely to keep the cripple alive and comfortable but to enable him, if we can, to take his place in society-to support himself, and to lead as full a life as possible. The International Council for the Welfare of Cripples exists to foster schemes which promote these aims. Supported partly by the United Nations but largely from voluntary contributions, the council does not offer direct service to patients, but seeks to coordinate and help the efforts of local and specialised organisations. It provide translations and films, and engages in instruction and propaganda to the public. Now in London it is holding its seventh world congress, with papers on many aspects of disabilities and their treatment, and a public exhibitioll at Central Hall, Westminster, which will be open until the end of this week (Friday and Saturday, 10.30 A.M. to 6.30 P.M.). The British Government exhibit illustrates the mans services organised by the State, and other countries have corresponding displays. The Bulova school of watch- making shows how cripples have : been so trained that

Upload: duongthuan

Post on 02-Jan-2017

215 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: ENDOCRINE TRANSPLANTATION

180

procedure than agglutination. An advantage is that otherheterogenetic antibodies do not interfere with the reaction.By any method of serological diagnosis, a rising titre

is more significant than an isolated reading. Titres canvary widely with slight alterations in technique ; but asheep-cell-agglutinin titre of over 1 in 30,15 and a haemo-lysin titre to ox cells of over 1 in 40,21 are diagnostic inmost cases.

22. Murray, J. E., Merrill, J. P., Harrison, J. H. Surgical Forum.Chicago, 1956 ; vol. 6, p. 432.

23. Dempster, W. J. Brit. med. J. 1951, ii, 1041.24. Loeb, L. The Biological Brain of Individuality. Springfield,

Ill., 1945.25. Medawar, P. B. J. Anat., Lond. 1944, 78, 176.26. Billingham, R. E., Krohn, P. L., Medawar, P. B. Brit. med. J.

1951, ii, 1049.27. Halsted, W. S. J. exp. Med. 1909, 11, 175.28. Turner, C. D. Anat. Rec. 1939, 73, 145.29. Woodruff, M. F. A., Woodruff, H. G. Phil. Trans. B. 1950,

234, 559.30. Broster, L. R., Gardiner-Hill, H. Brit. med. J. 1946, ii, 570.31. Bland, W. H., Chesson, A. L., Crow, J. B. N. C. med. J.

1950, 11, 501.

ENDOCRINE TRANSPLANTATION

IT is well known that homotransplants, except ojcornea, cartilage, and blood-vessels, do not survive inman unless the donor and recipient are identical twins.Even between identical twins very few successful trans-plants of whole organs have been performed-one was akidney transplantation reported last year by Murrayet al.22 Dempster 23 pointed out that homotransplantscould survive in the lower orders of animal life, but thatthey became increasingly unsuccessful as the phylo-genetic scale was ascended. Discussing the reasons forthe disintegration of transplanted tissues and organs, hecited Loeb’s 24 belief in the importance of the local cellularreaction, but inclined to the view that it was due to anactively acquired immunity reaction on the part of thehost. This hypothesis is strongly supported by the workof Medawar,25 who showed that in rabbits second-crophomotransplants of skin from the same donor to the samerecipient disintegrated more rapidly than the first crop.He afterwards found that the local application of cortisoneto skin-grafts in rabbits prolongs the survival.26The consistent failure of homotransplants to survive

in man has not deterred investigators in this field, andit is not surprising that the transplantation of endocrineglands should have received particular attention. As

they are relatively independent of a nerve-supply fortheir proper functioning, and discharge their secretionsdirectly into the circulation, their transplantationpresents no difficult technical problems. Ever since1909, belief in the ultimate, feasibility of such a pro-cedure has been encouraged by Halsted’s so-called law 27which states, on very limited evidence, that the trans-plantation of an endocrine gland is more likely to besuccessful if there exists in the host a deficiency of itsparticular secretion. This " law " is supported to someextent by the work of Turner,28 and has been explained byWoodruff and Woodruff 29 on the ground that a highcirculating level of the appropriate trophic hormone fromthe pituitary promotes the survival of transplantedendocrine tissue. Halsted’s original observations were,however, based on the transplantation of parathyroids,which are believed not to be the targets of any pituitaryhormone.

There is as yet no convincing evidence of permanentsurvival of transplanted endocrine glands in man althoughtherapeutic activity has undeniably been observed forlimited periods-for example, in the case of Addison’sdisease which Broster and Grardiner-Hill so claimed tohave cured by adrenal transplantation, Bland et al.31claimed the cure of a case of postoperative hypopara-thyroidism by the implantation into the rectus muscleof parathyroid tissue from a 29-year-old man who hadjust died, but their report covered only four months’follow-up.

y

It has been suggested that fcetal tissue, being le, _antigenic than fully differentiated tissue, would be lessliable to destruction by an immune reaction in the host.Dempster 23 is pessimistic about this line of research, butastonishing results have been claimed by Kadyseva of the Jaroslav Medical Institute who has implantel]pituitary glands from 4-5-month-old fcetuses into threepituitary dwarfs, all of whom are said to have respondedby substantial acceleration of growth.Kooreman and Gaillard 33 cultivated foetal parathyroid

tissue in media to which increasing amounts of serumfrom the prospective recipient had been added in thehope of

" acclimatising " the tissue to its future environ.ment. They reported 42 grafts in 29 hypoparathyroiupatients, in 21 of whom the result had been observed forat least a year. The grafts were apparently entirelysuccessful in 7 of these patients, all below the age of 3h,This lead has now been followed by Escamilla et al.,34who have applied the method to 14 transplants in ilcases of surgical hypoparathyroidism. 6 of these trans-plants were taken from the parathyroids of infants whowere stillborn or who died shortly after birth, and 8 wereobtained from parathyroid adenomas removed at opera.tion. The parathyroid tissue was grown in a basic saltsolution in the presence of increasing concentrations ofrecipient serum, and implantation was carried out afterabout two weeks of tissue-culture. The implants wenmade into pockets in the sheath of the axillary vein, thenumber of fragments implanted varying from 13 to 80,The results were on the whole disappointing. In onr

case symptoms of hypoparathyroidism had not returnedafter nineteen months, but unfortunately the diagnosiswas not confirmed biochemically before the implantation,In a second patient convincing biochemical improvementwas obtained -for about a year, and partial relief hacontinued for thirteen months after a second implant.Transient improvement lasting for one to six weeks wasseen in 6 cases, and no improvement whatever in theremaining 3.

It cannot be said that this latest excursion into thedifficult but ever-tempting province of endocrine trans.plantation offers much more hope of useful therapeuticresults than have earlier experiments in this direction,But the small measure of success which Escamilla andhis colleagues have achieved will no doubt encourageother workers in this field.

32. Kadyseva, N. M. Probl. Endokr. Gormonoter. 1956, 2, 90.33. Kooreman, P. J., Gaillard, P. J. Arch. chir. neerland. 1950,

2, 326.34. Escamilla, R. F., Kempe, C. H., Crane, J., Goldman, L., Gordan.

G. S. Ann. intern. Med. 1957, 46, 649.

DISABILITY

TODAY it is increasingly realised that, when we havefailed to prevent crippling, our duty is not merely to keepthe cripple alive and comfortable but to enable him, ifwe can, to take his place in society-to support himself,and to lead as full a life as possible. The InternationalCouncil for the Welfare of Cripples exists to fosterschemes which promote these aims. Supported partlyby the United Nations but largely from voluntarycontributions, the council does not offer direct serviceto patients, but seeks to coordinate and help the effortsof local and specialised organisations. It providetranslations and films, and engages in instruction andpropaganda to the public. Now in London it is holdingits seventh world congress, with papers on many aspectsof disabilities and their treatment, and a public exhibitiollat Central Hall, Westminster, which will be open untilthe end of this week (Friday and Saturday, 10.30 A.M. to6.30 P.M.).The British Government exhibit illustrates the mans

services organised by the State, and other countries havecorresponding displays. The Bulova school of watch-making shows how cripples have : been so trained that