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PARTIAL-THICKNESS SKIN GRAFTING OF FINGERTIP INJURIES
705 this hypothesis, for our patient was in strongly positive calcium balance when he had severe hypocalcaemia and comes. hypomagnesæmia, this suggests a disturbance of bloodbone equilibrium with inadequate release of calcium from level factors the are The regulating plasma-magnesium still poorly understood both in health and disease. Several bone to blood-stream, which may be corrected by raising workers (Dunn and Walser 1966, Freeman and Pearson the plasma-magnesium level. Two other conclusions may be drawn from this study. 1966, Evans and Watson 1966) have emphasised that hypomagnesaemia is not invariably associated with Firstly, hypomagnesaemia should be considered as a cause magnesium deficiency—i.e., appreciable total body- of convulsions in infancy when hypocalcaemic tetany fails deficit of magnesium—and the two expressions should not to respond to adequate intravenous injections of calcium For example, low plasma- salts. Secondly, the finding of three apparently identical be used synonymously. levels be induced experimentally in cases in a relatively short time in three separate centres may magnesium animals without the simultaneous production of negative suggests that this metabolic disorder may be commoner magnesium balances (Richardson and Welt 1965, Dawborn than has been realised. Prof. C. E. Dent, Dr. L. B. Strang, and Dr. Simon Yudkin were in and Watson 1967). Furthermore, a pronounced reduction in muscle-magnesium concentration has been described charge of this patient at various times; we are most grateful for their help and advice in his investigation and care. We thank Dr. R. A. without hypomagnesaemia (Macintyre et al. 1961). Evans for help in the early stages of the investigation; and the bioNevertheless, low plasma-magnesium levels are usually chemists, dietitians and nursing staff of the metabolic and paediatric associated with some degree of magnesium deficiency, and wards at University College Hospital for their help with the balance intestinal malabsorption is by far the commonest single studies and care of the child. Since preparing this report for publication we have been kindly cause of such hypomagnesaemia in clinical experience. sent by Dr L. Paunier and his co-authors the typescript of their Low plasma-magnesium levels have been reported in paper Primary Hypomagnesasmia with Secondary Hypoca1caemia in an Infant. This paper, which has not yet been published, is a full many other conditions (see Freeman and Pearson 1966), but there is no reason to suspect any of these in our patient. account of the investigations performed in their patient. Their independent conclusions are essentially the same as our own. The results of the magnesium balance studies suggest Requests for reprints should be addressed to L. W., Medical Unit, that this patient has a specific intestinal malabsorption of University College Hospital Medical School, London W.C.I. REFERENCES magnesium since there was no other clinical evidence of Yu, J. S. (1965) Archs Dis. Childh. 40, 286. malabsorption, the faecal fat was normal, and calcium Davis, J. A., Harvey, D. R., J. K., Watson, L. (1967) Unpublished. absorption was normal. In the absence of magnesium Dawborn, Dent, C. E., Harper, C. M., Philpot, G. R. (1961) Q. Jl Med. 30, i. balance data from normal children, full interpretation of Dick, M. (1967) J. clin. Path. (in the press). these results is difficult; but one would expect a constantly Dunn, M. J., Walser, M. (1966) Metabolism, 15, 884. Evans, R. A., Watson, L. (1966) Lancet, i, 522. positive magnesium balance during the period of rapid Fletcher, R. F., Henly, A. A., Sammons, H. G., Squire, J. R. (1960) ibid. i, 522. growth in the first 18 months of life. Our patient was in Freeman, R. M., Pearson, M. (1966) Am. J. Med. 41, 645. positive magnesium balance when his magnesium intake Heaton, F. W. (1965) Clin. Sci. 28, 543. was high in June and July, 1965, and in August, 1966; but Fourman, P. (1965) Lancet, ii, 50. L’Estrange, J. L., Axford, R. F. E. (1964) J. agric. Sci., Camb. 62, 353. his overall external magnesium balance was approximately MacDonald, M. A., Watson, L. (1966) Clin. chim. Acta, 14, 233. zero in August, 1965, and slightly negative in August, Macintyre, I., Davidsson, D. (1958) Biochem. J. 70, 456. S., Booth, C. C., Read, A. E. (1961) Clin. Sci. 20, 297. 1966, when he was taking a normal amount of magnesium Paunier,Hanna, L., Radde, I. C., Kooh, S. W., Fraser, D. (1965) Abstract of for his age. These changes in magnesium balance are metabolic session, Society for Pediatric Research, Philadelphia; p. 32. Reifenstein, E. C., Albright, F. A., Wells, S. L. (1945) J. clin. Endocr. 5, 367. more than sufficient to account for the accompanying fall J. A., Welt, L. G. (1965) Proc. Soc. exp. Biol. Med. 118, 512. in plasma-magnesium levels. Whetherthe failure to Richardson, Salet, J., Polonovski, C., de Gouyon, F., Pean, G., Melekian, B., Fournet, J-P. (1966) Archs fr. pediat. 23, 749. absorb magnesium normally from the gut is an isolated R. H. (1961) Nature, Lond. 191, 181. Smith, and primary defect or merely one aspect of a more wide- Watson, L. (1966) J. R. Coll. Physns, Lond. 1, 28. spread disease is not yet established. The observation that throughout the study his urinary magnesium excretion was remarkably low not only excludes urinary loss of magnesium as the cause of his hypomagnesaemia but also indicates effective renal conservation. PARTIAL-THICKNESS SKIN GRAFTING Clearly hypocalcaemia followed hypomagnesaemia in OF FINGERTIP INJURIES this patient and responded to treatment with magnesium JOHN R. SALAMAN (but not calcium) supplements. This has been reported M.A., M.B. Cantab. before in cattle (Smith 1961), sheep (L’Estrange and FORMERLY SENIOR HOUSE-OFFICER TO THE ACCIDENT SERVICE, Axford 1964), and man (Fletcher et al. 1960, Heaton and ADDENBROOKE’S HOSPITAL, CAMBRIDGE Fourman 1965), though species differences do exist; for in rats hypomagnesæmia may be followed by hyperA follow-up of 51 patients who had susSummary tained fingertip injuries which had been Heaton calcaemia (Macintyre and Davidsson 1958, 1965). treated means of immediate partial-thickness skin The mechanism of production of hypocalcaemia which by apparently depends on the presence of hypomagnesaemia grafting showed that satisfactory results had been is unknown. Heaton and Fourman noted that the rise in obtained. The method is recommended for routine use by the plasma-calcium level which followed treatment with accident-officers. Introduction magnesium in two of their adult patients with malTHE partly amputated fingertip is a common injury. absorption was associated with a negative calcium balance. This suggested to them that the additional calcium was Methods of treatment include simple conservative derived from bone rather than gut. They concluded that measures, proximal reamputation, pedicle grafting, and "magnesium deficiency interferes with the release of free skin grafting. The simplest procedure is to allow calcium from the bone ". Our studies are consistent with healing to take place by granulation. This may take many
genetic characteristics, although consanguinity
uncommon
in the social group from which
our
is not
patient
—
—
N3
706 weeks to complete, and, since the final result can be a hard insensitive scar, the method is usually condemned (Brauer 1964) though it has been advocated for young children, and some good results have been reported in adults (Bojsen-Moller et al. 1961). An alternative procedure is to shorten the digit further, and to suture the skin flaps so obtained. Healing is usually rapid, but residual tenderness is often a problem. Pedicle grafting has its advocates (Flatt 1959) and the results are usually good. The method, however, calls for two operations and a surgeon with skill and experience. By the time healing is complete and finger mobility is regained, much time may have been lost from work. Small full-thickness grafts give good results in many instances (Sturman and Duran 1963); but partial-thickness skin grafting is an even simpler procedure, and the graft is more likely to take in unfavourable circumstances. This method has been criticised for producing unstable, tender grafts with poor sensation (Flatt 1959), and has been classed as unsuitable for covering injuries where bone has been exposed (Robertson 1962). Good results have been reported, however, with partial-thickness skin grafting (Mandal 1965, Moynihan 1961), and when compared with other procedures, the results are frequently better (Sturman and Duran 1963). Partial-thickness grafts may also be used with advantage for covering nail bed injuries
(Flatt 1955). A further method of treatment is the resuturing of the amputated finger tip, if it should be available. It must first be defatted as for a full-thickness graft, but a successful take is by no means assured (Robertson 1962). Patients and Methods From
to June, 1965, 101 patients underwent partial-thickness skin grafts as outpatients in the Accident Service. Satisfactory records were available for 65 patients, of
January, 1962,
whom 51 attended for examination on request. These had received 55 grafts. The operations had been carried out by 17 different accident officers, and the follow-up period was one to four and a half years. There were 33 males and 18 females, and their ages ranged from two to sixty-nine years. Half the injuries occurred at work from various causes, but of those sustained at home, more than a third were caused by a slamming door. The nail or nailbed had been directly injured in 25; in 18, bone had been exposed or amputated. The digits most commonly affected were the dominant and non-dominant middle fingers and the dominant index finger. All patients with fingertip amputation were treated with partial-thickness skin grafts as outpatients. Children usually received a general anaesthetic, but all other patients were given " a ring block " of 1 % lignocaine at the base of the injured finger, combined with local infiltration of anaesthetic at the donor site. The wound was cleaned thoroughly, and any protruding phalanx was nibbled away until it was hidden by fat. The graft was taken from the forearm with a miniature skingraft knife (Down’s), laid on paraffin gauze, and then sutured into position. With small grafts, sutures were sometimes omitted. A firm pressure-dressing completed the operation, and a non-adherent dressing was applied to the donor site. After two weeks, the graft could usually be left exposed but protected from injury by a finger-stall until it was less tender.
took two months to heal owing to the presence of a previously undetected sequestrum. Once the fragment had been removed healing was rapid; this was the only patient who required further surgery. Just less than threequarters of all the grafts had therefore " taken " satisfactorily without any complications. The delayed healing in the others was usually due to failure of part of the graft or to sepsis in the wound. The wounds in these patients were treated with antiseptic soaks and frequent dressings until they had healed. One graft failed completely owing to bleeding under the graft, and the wound took six weeks to heal by granulation. This patient had been on anticoagulants after a recent cardiac infarction. 21% of the patients were able to continue with their jobs without a break, and a further 37% returned to work within two weeks. By the end of three weeks, 79% were at their former occupations. The remainder (8 patients) were all back by six weeks, with the exception of the patient who had to have further surgery. He was away eleven weeks. Late Results
Cracking and sensitivity to cold.-29% of the patients had noticed some cracking of the graft, usually in cold weather or after exposure to detergents or industrial chemicals, but only 4 patients needed to protect their grafts at work. 14% of the patients complained of numbness in the cold weather. Texture-76% of the grafts were soft and supple, and often differed little from normal digital skin. 20% had rather firmer grafts which were quite thick and horny in places. The graft was thin and unsupported in only 4% (2 patients). In many instances the graft had contracted considerably. In 4 instances, quite large grafts had become reduced to a mere band of thickened skin under the tip of the nail. Pigmentation was present in 17% of the grafts, and was particularly gross in 1 patient. Nail.-25 patients had sustained injuries to the nail bed. These had been covered with partial-thickness skin grafts which had later become incorporated into the nail bed, and covered by nail. In 2 patients, however, the nail had parted company with the graft and had formed an un-
Results
Early Results The graft was described as having " taken " when " the whole of the graft was intact, attached, dry and stable " (Lunn 1965). This had happened within two weeks in 42% of the patients, and within three weeks in 72%. In the remaining 28% (15 patients) the grafts had all" taken " within six weeks, with the exception of one graft which
~
Fig. 1-Testing for
tenderness.
707
sightly hood over it. In 5 further patients the nail end had become bent over, and in 2 others the nail was absent altogether. for Function Many tests have been described for assessing the sensitivity of digital skin grafts (Mannerfelt 1962, Sturman et al. 1963, Porter 1966). Moberg (1958) believes that only three tests are of any practical value-namely, twopoint discrimination, a picking-up test, and a sweating test. In this follow-up, the first two were carried out, but the sweating test was omitted. A simple test for light touch was substituted in which the graft was gently stroked with cottonwool, and the number of times this was felt during ten attempts was recorded. This was compared with the score from the corresponding finger of the opposite hand, and if it differed by more than three, it was considered Tests
that
sensory loss had been demonstrated. measurements of the degree of remaining tenderness in the graft are difficult to carry out, and the results may be misleading (Moberg 1964). Sturman and Duran (1963) describe an algesiometer of their own invention, construction from a ballpoint pen. A modificasome
Fig. 3-The pain thresholds of the skin grafts.
Objective
The
proportion of patients with tender grafts is indicated.
laid emphasis on the value of this test for determining the usefulness of an injured digit. Light touch.-Using the method described above, a significant degree of sensory loss was found in 25 % of the grafts. Tenderness.-62% of the patients denied any tenderness whatsoever. A further 29% admitted that the graft was sometimes tender, when knocked. In 9% (5 patients) the tenderness was bad enough to interfere with the patient’s daily routine, but not so severe as to force him to change his employment. Injuries which included bone injury were no more likely to have residual tenderness after grafting than injuries of skin and pulp alone. Using the simple algesiometer, the grafts were tested for tenderness ; the results were compared with the patient’s subjective impression (fig. 3). No close association was demonstrated; half the patients who complained of tenderness did not register pain on testing until at least 30 g. had been applied to the point. Discussion
Fig. 2-Two-point discrimination. In each
that found
the value obtained from the graft is the corresponding control area.
case
at
plotted against
tion of this method was used in the present follow-up. The point of a pin replaces the ballpoint, and the cartridge is spring-loaded inside the casing which bears a scale. With the point on the skin, an increasing force may be gradually applied, and a reading taken as soon as pain is
experienced (fig. 1). Two-point discrimination.-This time-honoured test of Weber was carried out with a pair of dividers, and readings were taken on the graft and the corresponding digit on the other hand (fig. 2). 70% of the patients could distinguish between points 3 mm. apart, and over 90% could distinguish between points 4 mm. apart. It was also apparent that patients who had only moderate sensation in their normal skin had less sensitive grafts. Picking-up tests.-24 patients with injuries to the tip of their thumb or index finger were asked to pick up a selection of small objects from a table and to place them in a box. 71% (17 patients) managed this perfectly satisfactorily, but the others all experienced some difficulty or substituted the middle finger for the index. Moberg (1964)
The advantages of partial-thickness skin grafting are that it can be speedily carried out and that it requires neither a general anaesthetic nor the patient’s admission to hospital. The whole treatment is completed at the one operation and the patient makes an early return to work. Even primary closure after further shortening of the phalanx; results in a greater time lost from work (BIody 1960, Sturman and Duran 1963). The late results seem satisfactory, and over 80% of the patients were pleased with the outcome. There were 7 patients, however, who were dissatisfied with the final result. Their reasons were poor cosmetic appearance (3 patients), tenderness (2 patients), and cracking and numbness of the graft (1 patient each). The high level of sensitivity obtained with some of the grafts was a most interesting feature. The grafts had been taken from the fo rm, where sensation is fairly crude and two-point discrimination is in the order of 30-40 mm. The site of the donor skin is evidently unimportant, and the level of sensation that is eventually gained by the graft depends principally on the level that existed before at the recipient site. Local skin-flaps or free toe-grafts have been recommended as likely to give a better final result, since the donor skin is taken from a highly sensitive area and bears numerous tactile organs (Reid 1956, McCash 1959). In practice, the level of sensation with local pedicle grafts is no better than that obtained with free skin grafts from more remote sites (Mannerfelt 1962, Sturman and Duran 1963), and pedicle flaps from the dorsum of the hand
708 remain very insensitive (McFarlane et al. 1962). This follow-up supports fully the conclusions of Moynihan (1961) that partial-thickness skin grafting is the treatment of choice for the common fingertip injury. Both the early and late results were good. Accident officers should be encouraged to carry out this simple operation whenever digital skin cover is required.
NEW EVIDENCE
can
I should like to record my thanks support and encouragement.
to
Mr. A. H. G.
Murley for his
REFERENCES
Bojsen-Moller, J., Pers, M., Schmidt, A. (1961) Acta chir. scand. 122, 177. Brauer, S. D. (1964) Ohio med. J. 60, 39. Brody, G. S., Cloutier, A. M., Woolhouse, F. M. (1960) Plast. reconstr. Surg. 26, 80. Flatt, A. E. (1955) Br. J. plast. Surg. 8, 34. (1959) The Care of Minor Hand Injuries. London. Lunn, J. A. (1965). Br. med. J. ii, 1352. McCash, C. R. (1959) Br. J. plast. Surg. 11, 322. McFarlane, R. M., et al. (1962) J. Bone Jt Surg. 44A, 1365. Mandal, A. C. (1965) Acta chir. scand. 129, 325. Mannerfelt, L. (1962) Br. J. plast. Surg. 15, 136. Moberg, E. (1958) J. Bone Jt Surg. 40B, 454. (1964) ibid. 46A, 817. Moynihan, B. J. (1961) Br. med. J. ii, 802. Porter, R. W. (1966) ibid. ii, 927. Reid, D. A. C. (1956) Br. J. plast. Surg. 9, 11. Robertson, D. C. (1962) Can. J. Surg. 5, 379. Sturman, M. J., Duran, R. J. (1963) J. Bone Jt Surg. 45A, 289. —
-
Hypothesis THE MASKING OF ANTIGENS ON TROPHOBLAST AND CANCER CELLS The pregnant female fails to reject foetal trophoblast as an allograft, although maternal lymphocytes respond in vitro to trophoblast as they do to allogeneic tissue. Host lymphocytes respond similarly to gestational choriocarcinoma in vitro. A peritrophoblastic coat of sialomucin has been identified in Summary
vivo and a similar substance on the surface of cancer cells is known to confer a high electronegative surface charge. Since lymphocytes also carry a negative charge, it is suggested that trophoblast escapes attack in vivo by electrochemical repulsion of maternal lymphocytes. It is also suggested that tumour antigens escape recognition in like manner. These observations call for a re-evaluation of some fundamental biological concepts.
We have observed that when trophoblast is grown in vitro, it undergoes gross cytolysis in the presence of allogeneic or maternal lymphocytes.This " allogeneic inhibition "indicates that trophoblast expresses antigenicity which is detectable by maternal cells. Postgestational choriocarcinoma, a highly malignant allograft
which continues to grow in vivo even when the host has been successfully immunised against paternal antigens,8 likewise undergoes cytolysis in the presence of host lymphocytes in vitro. Choriocarcinoma therefore seems to express antigenicity like normal trophoblast. We suggest that cytolysis of normal and malignant trophoblast happens in the presence of host lymphocytes in tissue culture, but not in vivo, because the fibrinoid coat around trophoblastic cells is removed during trypsinisation before culture. Trypsinisation did not make syngeneic cells susceptible to inhibition by lymphocytes. We therefore conclude that trophoblastic cells, like other cells, express histocompatibility antigens and this supports the view of Kirby et awl.9 that the foetal/maternal immunological barrier is non-cellular. Since histocompatibility antigens are relatively insoluble,Io 11 we suggest that the barrier operates, not by preventing the release of antigens into the circulation, but by preventing host lymphocytes from making cell-to-cell contact with trophoblast. If placental fibrinoid can effectively mask major histocompatibility differences between foetal and maternal tissues, it follows that weaker antigenic factors may be readily masked by a similar mechanism. It is therefore of considerable interest that a sialomucin similar to placental fibrinoid has been found on the surface of malignant cells 12 and that such a coating confers a negative charge on cell surfaces.
Hypothesis Our hypothesis may therefore be summarised as follows: pericellular sialomucins present an important electrochemical barrier to immunologically competent cells, not only in normal mammalian pregnancy but also in many, if not all, forms of malignant disease. The hypothesis seems to be consistent with, and to integrate, a considerable body of experimental evidence; some of this evidence is presented here. DISTRIBUTION AND PHYSICAL PROPERTIES
INTRODUCTION
OF SIALOMUCINS
THE fcetal maternal relationship in mammals provides model of the well-tolerated allograft. Failure of immunological mechanisms to reject the conceptus has prompted several hypotheses but the only one widely accepted and consistent with confirmed observations is that some sort of antigen barrier exists between maternal and foetal tissues.1 Opinion has been divided as to whether this barrier is cellular or non-cellular: some workers have concluded that the fcetal tissue in contact with maternal cells (i.e., the trophoblastic epithelium) performs this function by failing to express antigenicity in allogeneic situations 2-4 while others have suggested that a fibrinoid coating round trophoblastic cells acts as a barrier and prevents the egress of foetal transplantation antigens into the mother ".55
The presence of fibrinoid material along the foetal-maternal interface has long been recognised and its possible immunological significance was suggested by Bardawil and Toy." Kirby et al. noted that it provided a complete investment of trophoblastic cells. Bradbury et awl. found it to be an amorphous, electron-dense sialomucin which stained with periodic-acid/1 Schiff and Hale colloidal-iron reactions. They also demonstrated a striking increase in placental fibrinoid in hybrid matings, and we have found that when normal, early human trophoblast is incubated in vitro with allogeneic fibroblasts, large amounts of Hale-positive material appear, suggesting thats its production is increased in response to histoincompatibility.’ Sialomucins are found in other immunologically atypical
a
"
1. Billingham, R. E. New Engl. J. Med. 1964, 270, 667, 720. 2. Simmons, R. L., Russell, P. S. Ann. N.Y. acad. Sci. 1962, 99, 717. 3. Schlesinger, M. J. Immun. 1964, 93, 255. 4. Lanman, J. T. J. Pediat. 1965, 66, 525. 5. Bradbury, S., Billington, W. D., Kirby, D. R. S. J. R. microsc. Soc. 1965, 84, 199.
6. 7. 8. 9. 10. 11. 12.
13.
Currie, G. A., Bagshawe, K. D. Unpublished, 1967. Möller, G., Möller, E. Ann. Med. exp. Fenn. 1966, 44, 181. Hackett, E., Beech, M. Br. med. J. 1961, ii, 1123. Kirby, D. R. S., Billington, W. D., Bradbury, S., Goldstein,
D.
J.
Nature, Lond. 1964, 204, 548. Möller, G. J. exp. Med. 1961, 114, 415. Batchelor, J. R. Br. med. Bull. 1965, 21, 100. Gasic, G., Beydak, T. in Biological Interactions in Normal and Neoplastic Growth (edited by M. J. Brennan and W. L. Simpson); p. 709. London, 1961. Bardawil, W. A., Toy, B. L. Ann. N.Y. Acad. Sci. 1959, 80, 197.
genetic characteristics, although consanguinity
uncommon
in the social group from which
our
is not
patient
—
—
N3
706 weeks to complete, and, since the final result can be a hard insensitive scar, the method is usually condemned (Brauer 1964) though it has been advocated for young children, and some good results have been reported in adults (Bojsen-Moller et al. 1961). An alternative procedure is to shorten the digit further, and to suture the skin flaps so obtained. Healing is usually rapid, but residual tenderness is often a problem. Pedicle grafting has its advocates (Flatt 1959) and the results are usually good. The method, however, calls for two operations and a surgeon with skill and experience. By the time healing is complete and finger mobility is regained, much time may have been lost from work. Small full-thickness grafts give good results in many instances (Sturman and Duran 1963); but partial-thickness skin grafting is an even simpler procedure, and the graft is more likely to take in unfavourable circumstances. This method has been criticised for producing unstable, tender grafts with poor sensation (Flatt 1959), and has been classed as unsuitable for covering injuries where bone has been exposed (Robertson 1962). Good results have been reported, however, with partial-thickness skin grafting (Mandal 1965, Moynihan 1961), and when compared with other procedures, the results are frequently better (Sturman and Duran 1963). Partial-thickness grafts may also be used with advantage for covering nail bed injuries
(Flatt 1955). A further method of treatment is the resuturing of the amputated finger tip, if it should be available. It must first be defatted as for a full-thickness graft, but a successful take is by no means assured (Robertson 1962). Patients and Methods From
to June, 1965, 101 patients underwent partial-thickness skin grafts as outpatients in the Accident Service. Satisfactory records were available for 65 patients, of
January, 1962,
whom 51 attended for examination on request. These had received 55 grafts. The operations had been carried out by 17 different accident officers, and the follow-up period was one to four and a half years. There were 33 males and 18 females, and their ages ranged from two to sixty-nine years. Half the injuries occurred at work from various causes, but of those sustained at home, more than a third were caused by a slamming door. The nail or nailbed had been directly injured in 25; in 18, bone had been exposed or amputated. The digits most commonly affected were the dominant and non-dominant middle fingers and the dominant index finger. All patients with fingertip amputation were treated with partial-thickness skin grafts as outpatients. Children usually received a general anaesthetic, but all other patients were given " a ring block " of 1 % lignocaine at the base of the injured finger, combined with local infiltration of anaesthetic at the donor site. The wound was cleaned thoroughly, and any protruding phalanx was nibbled away until it was hidden by fat. The graft was taken from the forearm with a miniature skingraft knife (Down’s), laid on paraffin gauze, and then sutured into position. With small grafts, sutures were sometimes omitted. A firm pressure-dressing completed the operation, and a non-adherent dressing was applied to the donor site. After two weeks, the graft could usually be left exposed but protected from injury by a finger-stall until it was less tender.
took two months to heal owing to the presence of a previously undetected sequestrum. Once the fragment had been removed healing was rapid; this was the only patient who required further surgery. Just less than threequarters of all the grafts had therefore " taken " satisfactorily without any complications. The delayed healing in the others was usually due to failure of part of the graft or to sepsis in the wound. The wounds in these patients were treated with antiseptic soaks and frequent dressings until they had healed. One graft failed completely owing to bleeding under the graft, and the wound took six weeks to heal by granulation. This patient had been on anticoagulants after a recent cardiac infarction. 21% of the patients were able to continue with their jobs without a break, and a further 37% returned to work within two weeks. By the end of three weeks, 79% were at their former occupations. The remainder (8 patients) were all back by six weeks, with the exception of the patient who had to have further surgery. He was away eleven weeks. Late Results
Cracking and sensitivity to cold.-29% of the patients had noticed some cracking of the graft, usually in cold weather or after exposure to detergents or industrial chemicals, but only 4 patients needed to protect their grafts at work. 14% of the patients complained of numbness in the cold weather. Texture-76% of the grafts were soft and supple, and often differed little from normal digital skin. 20% had rather firmer grafts which were quite thick and horny in places. The graft was thin and unsupported in only 4% (2 patients). In many instances the graft had contracted considerably. In 4 instances, quite large grafts had become reduced to a mere band of thickened skin under the tip of the nail. Pigmentation was present in 17% of the grafts, and was particularly gross in 1 patient. Nail.-25 patients had sustained injuries to the nail bed. These had been covered with partial-thickness skin grafts which had later become incorporated into the nail bed, and covered by nail. In 2 patients, however, the nail had parted company with the graft and had formed an un-
Results
Early Results The graft was described as having " taken " when " the whole of the graft was intact, attached, dry and stable " (Lunn 1965). This had happened within two weeks in 42% of the patients, and within three weeks in 72%. In the remaining 28% (15 patients) the grafts had all" taken " within six weeks, with the exception of one graft which
~
Fig. 1-Testing for
tenderness.
707
sightly hood over it. In 5 further patients the nail end had become bent over, and in 2 others the nail was absent altogether. for Function Many tests have been described for assessing the sensitivity of digital skin grafts (Mannerfelt 1962, Sturman et al. 1963, Porter 1966). Moberg (1958) believes that only three tests are of any practical value-namely, twopoint discrimination, a picking-up test, and a sweating test. In this follow-up, the first two were carried out, but the sweating test was omitted. A simple test for light touch was substituted in which the graft was gently stroked with cottonwool, and the number of times this was felt during ten attempts was recorded. This was compared with the score from the corresponding finger of the opposite hand, and if it differed by more than three, it was considered Tests
that
sensory loss had been demonstrated. measurements of the degree of remaining tenderness in the graft are difficult to carry out, and the results may be misleading (Moberg 1964). Sturman and Duran (1963) describe an algesiometer of their own invention, construction from a ballpoint pen. A modificasome
Fig. 3-The pain thresholds of the skin grafts.
Objective
The
proportion of patients with tender grafts is indicated.
laid emphasis on the value of this test for determining the usefulness of an injured digit. Light touch.-Using the method described above, a significant degree of sensory loss was found in 25 % of the grafts. Tenderness.-62% of the patients denied any tenderness whatsoever. A further 29% admitted that the graft was sometimes tender, when knocked. In 9% (5 patients) the tenderness was bad enough to interfere with the patient’s daily routine, but not so severe as to force him to change his employment. Injuries which included bone injury were no more likely to have residual tenderness after grafting than injuries of skin and pulp alone. Using the simple algesiometer, the grafts were tested for tenderness ; the results were compared with the patient’s subjective impression (fig. 3). No close association was demonstrated; half the patients who complained of tenderness did not register pain on testing until at least 30 g. had been applied to the point. Discussion
Fig. 2-Two-point discrimination. In each
that found
the value obtained from the graft is the corresponding control area.
case
at
plotted against
tion of this method was used in the present follow-up. The point of a pin replaces the ballpoint, and the cartridge is spring-loaded inside the casing which bears a scale. With the point on the skin, an increasing force may be gradually applied, and a reading taken as soon as pain is
experienced (fig. 1). Two-point discrimination.-This time-honoured test of Weber was carried out with a pair of dividers, and readings were taken on the graft and the corresponding digit on the other hand (fig. 2). 70% of the patients could distinguish between points 3 mm. apart, and over 90% could distinguish between points 4 mm. apart. It was also apparent that patients who had only moderate sensation in their normal skin had less sensitive grafts. Picking-up tests.-24 patients with injuries to the tip of their thumb or index finger were asked to pick up a selection of small objects from a table and to place them in a box. 71% (17 patients) managed this perfectly satisfactorily, but the others all experienced some difficulty or substituted the middle finger for the index. Moberg (1964)
The advantages of partial-thickness skin grafting are that it can be speedily carried out and that it requires neither a general anaesthetic nor the patient’s admission to hospital. The whole treatment is completed at the one operation and the patient makes an early return to work. Even primary closure after further shortening of the phalanx; results in a greater time lost from work (BIody 1960, Sturman and Duran 1963). The late results seem satisfactory, and over 80% of the patients were pleased with the outcome. There were 7 patients, however, who were dissatisfied with the final result. Their reasons were poor cosmetic appearance (3 patients), tenderness (2 patients), and cracking and numbness of the graft (1 patient each). The high level of sensitivity obtained with some of the grafts was a most interesting feature. The grafts had been taken from the fo rm, where sensation is fairly crude and two-point discrimination is in the order of 30-40 mm. The site of the donor skin is evidently unimportant, and the level of sensation that is eventually gained by the graft depends principally on the level that existed before at the recipient site. Local skin-flaps or free toe-grafts have been recommended as likely to give a better final result, since the donor skin is taken from a highly sensitive area and bears numerous tactile organs (Reid 1956, McCash 1959). In practice, the level of sensation with local pedicle grafts is no better than that obtained with free skin grafts from more remote sites (Mannerfelt 1962, Sturman and Duran 1963), and pedicle flaps from the dorsum of the hand
708 remain very insensitive (McFarlane et al. 1962). This follow-up supports fully the conclusions of Moynihan (1961) that partial-thickness skin grafting is the treatment of choice for the common fingertip injury. Both the early and late results were good. Accident officers should be encouraged to carry out this simple operation whenever digital skin cover is required.
NEW EVIDENCE
can
I should like to record my thanks support and encouragement.
to
Mr. A. H. G.
Murley for his
REFERENCES
Bojsen-Moller, J., Pers, M., Schmidt, A. (1961) Acta chir. scand. 122, 177. Brauer, S. D. (1964) Ohio med. J. 60, 39. Brody, G. S., Cloutier, A. M., Woolhouse, F. M. (1960) Plast. reconstr. Surg. 26, 80. Flatt, A. E. (1955) Br. J. plast. Surg. 8, 34. (1959) The Care of Minor Hand Injuries. London. Lunn, J. A. (1965). Br. med. J. ii, 1352. McCash, C. R. (1959) Br. J. plast. Surg. 11, 322. McFarlane, R. M., et al. (1962) J. Bone Jt Surg. 44A, 1365. Mandal, A. C. (1965) Acta chir. scand. 129, 325. Mannerfelt, L. (1962) Br. J. plast. Surg. 15, 136. Moberg, E. (1958) J. Bone Jt Surg. 40B, 454. (1964) ibid. 46A, 817. Moynihan, B. J. (1961) Br. med. J. ii, 802. Porter, R. W. (1966) ibid. ii, 927. Reid, D. A. C. (1956) Br. J. plast. Surg. 9, 11. Robertson, D. C. (1962) Can. J. Surg. 5, 379. Sturman, M. J., Duran, R. J. (1963) J. Bone Jt Surg. 45A, 289. —
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Hypothesis THE MASKING OF ANTIGENS ON TROPHOBLAST AND CANCER CELLS The pregnant female fails to reject foetal trophoblast as an allograft, although maternal lymphocytes respond in vitro to trophoblast as they do to allogeneic tissue. Host lymphocytes respond similarly to gestational choriocarcinoma in vitro. A peritrophoblastic coat of sialomucin has been identified in Summary
vivo and a similar substance on the surface of cancer cells is known to confer a high electronegative surface charge. Since lymphocytes also carry a negative charge, it is suggested that trophoblast escapes attack in vivo by electrochemical repulsion of maternal lymphocytes. It is also suggested that tumour antigens escape recognition in like manner. These observations call for a re-evaluation of some fundamental biological concepts.
We have observed that when trophoblast is grown in vitro, it undergoes gross cytolysis in the presence of allogeneic or maternal lymphocytes.This " allogeneic inhibition "indicates that trophoblast expresses antigenicity which is detectable by maternal cells. Postgestational choriocarcinoma, a highly malignant allograft
which continues to grow in vivo even when the host has been successfully immunised against paternal antigens,8 likewise undergoes cytolysis in the presence of host lymphocytes in vitro. Choriocarcinoma therefore seems to express antigenicity like normal trophoblast. We suggest that cytolysis of normal and malignant trophoblast happens in the presence of host lymphocytes in tissue culture, but not in vivo, because the fibrinoid coat around trophoblastic cells is removed during trypsinisation before culture. Trypsinisation did not make syngeneic cells susceptible to inhibition by lymphocytes. We therefore conclude that trophoblastic cells, like other cells, express histocompatibility antigens and this supports the view of Kirby et awl.9 that the foetal/maternal immunological barrier is non-cellular. Since histocompatibility antigens are relatively insoluble,Io 11 we suggest that the barrier operates, not by preventing the release of antigens into the circulation, but by preventing host lymphocytes from making cell-to-cell contact with trophoblast. If placental fibrinoid can effectively mask major histocompatibility differences between foetal and maternal tissues, it follows that weaker antigenic factors may be readily masked by a similar mechanism. It is therefore of considerable interest that a sialomucin similar to placental fibrinoid has been found on the surface of malignant cells 12 and that such a coating confers a negative charge on cell surfaces.
Hypothesis Our hypothesis may therefore be summarised as follows: pericellular sialomucins present an important electrochemical barrier to immunologically competent cells, not only in normal mammalian pregnancy but also in many, if not all, forms of malignant disease. The hypothesis seems to be consistent with, and to integrate, a considerable body of experimental evidence; some of this evidence is presented here. DISTRIBUTION AND PHYSICAL PROPERTIES
INTRODUCTION
OF SIALOMUCINS
THE fcetal maternal relationship in mammals provides model of the well-tolerated allograft. Failure of immunological mechanisms to reject the conceptus has prompted several hypotheses but the only one widely accepted and consistent with confirmed observations is that some sort of antigen barrier exists between maternal and foetal tissues.1 Opinion has been divided as to whether this barrier is cellular or non-cellular: some workers have concluded that the fcetal tissue in contact with maternal cells (i.e., the trophoblastic epithelium) performs this function by failing to express antigenicity in allogeneic situations 2-4 while others have suggested that a fibrinoid coating round trophoblastic cells acts as a barrier and prevents the egress of foetal transplantation antigens into the mother ".55
The presence of fibrinoid material along the foetal-maternal interface has long been recognised and its possible immunological significance was suggested by Bardawil and Toy." Kirby et al. noted that it provided a complete investment of trophoblastic cells. Bradbury et awl. found it to be an amorphous, electron-dense sialomucin which stained with periodic-acid/1 Schiff and Hale colloidal-iron reactions. They also demonstrated a striking increase in placental fibrinoid in hybrid matings, and we have found that when normal, early human trophoblast is incubated in vitro with allogeneic fibroblasts, large amounts of Hale-positive material appear, suggesting thats its production is increased in response to histoincompatibility.’ Sialomucins are found in other immunologically atypical
a
"
1. Billingham, R. E. New Engl. J. Med. 1964, 270, 667, 720. 2. Simmons, R. L., Russell, P. S. Ann. N.Y. acad. Sci. 1962, 99, 717. 3. Schlesinger, M. J. Immun. 1964, 93, 255. 4. Lanman, J. T. J. Pediat. 1965, 66, 525. 5. Bradbury, S., Billington, W. D., Kirby, D. R. S. J. R. microsc. Soc. 1965, 84, 199.
6. 7. 8. 9. 10. 11. 12.
13.
Currie, G. A., Bagshawe, K. D. Unpublished, 1967. Möller, G., Möller, E. Ann. Med. exp. Fenn. 1966, 44, 181. Hackett, E., Beech, M. Br. med. J. 1961, ii, 1123. Kirby, D. R. S., Billington, W. D., Bradbury, S., Goldstein,
D.
J.
Nature, Lond. 1964, 204, 548. Möller, G. J. exp. Med. 1961, 114, 415. Batchelor, J. R. Br. med. Bull. 1965, 21, 100. Gasic, G., Beydak, T. in Biological Interactions in Normal and Neoplastic Growth (edited by M. J. Brennan and W. L. Simpson); p. 709. London, 1961. Bardawil, W. A., Toy, B. L. Ann. N.Y. Acad. Sci. 1959, 80, 197.