- Email: [email protected]
Lead and Mental Handicap
365
THE LANCET
Lead and Mental Handicap of mental handicap in children are known, there remains a group of children in whom the aetiology is obscure. It is in this group that toxic chemicals, such as lead, could be a factor. Heavy intoxication by inorganic lead is a long-known cause of severe neurological and psychological disorders in children. Could exposure to lower amounts of inorganic lead, at times when the nervous system may be especially susceptible, during prenatal life and early childhood, result in mental handicap? In 1973 we found the evidence on subclinical lead poisoning inconclusive.’ What has happened since then, and are we any nearer a firm conclusion on the role of inorganic lead in mental handicap? The epidemiological studies published since then fall into two main groups-investigations of the lead exposure of children already diagnosed as mentally handicapped; and studies of the intelligence of schoolchildren exposed to different levels of environmental lead. In 1975 BEATTIE and co-workers2 reported a case-control study of mentally retarded children in Glasgow, a city that still had lead water-pipes in many of its older properties. Because the Glasgow water is plumbosolvent domestic drinking-water may contain large amounts of lead. 77 mentally retarded children aged 2-5, in whom no specific factor had been incriminated, formed the cases. A control group of 77 children was drawn from nonmentally-retarded healthy children matched for age, sex, and geographic location. No details are given on the source of these controls or on the methods of selection before matching. Home addresses during each child’s first year of life and the relevant pregnancy were obtained and a sample ALTHOUGH
some causes
1. Lancet, 1973, i, 87. 2. Beattie, A. D., Moore, M. R., Goldberg, A., Finlayson, M. J. W., Graham, J F., Mackie, E. M., Main, J. C., McLaren, D. A., Murdoch, R. M., Stewart, G. T., ibid. 1975, i, 589.
of water was taken from the kitchen cold-water tap at each address, where this was possible. in 13 of the 77 case-control pairs data on home water-lead levels were not available for one member of the pair. The mean water-lead levels in each trimester of pregnancy and in the first and second six months of life were consistently higher in the group of mentally retarded children than in the controls. BEATTIE and his colleagues concluded that the results strongly suggested that lead exposure causes mental retardation. This study attracted critical comment, mainly on the methodology. Specifically, the adequacy of the matching process used for the controls was questioned.3,4 A major objection, which the Glasgow workers themselves recognised,s,6 was their inability to include matching variables, such as maternal age and birth order, that may be relevant to the development of mental retardation. In another investigation the Glasgow group measured the lead in blood previously collected from the same children (for phenylketonuria screening) in the first two weeks of life. Blood-samples were found for 41 of the 77 mentally retarded children and 36 of the 77 controls, yielding only 24 matched pairs where both members had blood-samples, The distribution of blood-lead levels showed a trend towards higher levels in the mentally retarded group. The absence of blood-lead data on 77 out of 154 children means that any conclusions should be cautious ones. In a case-control study from New York, bloodleads were compared in three groups of 4-12-yearolds. The cases consisted of 64 mentally retarded children; 33 had no known cause for retardation while 31 had a "probable" cause. These children all had i.Q.s between 55 and 84 and had attended a clinic for the diagnosis and treatment of retardation. (Blood-lead analyses had been done routinely on all.) A control group of 30 children was drawn from a general pxdiatric outpatient clinic, such that they were within the same age-range, had a sex ratio comparable to that of the other group, and were not too ill to participate. Mean blood-lead levels were highest in the mentally retarded group with xtiology unknown; there was little difference in blood-lead between the controls and the mentally retarded children with probable xtiology. With no more than 33 children in each group, this is a rather small study and doubts must arise on how representative the findings are, expecially in respect of the controls. Biases may have been introduced by classification of those retarded children
3. Heasman, M. A. ibid. p. 982. 4. Primrose, D. A. ibid. 5. Goldberg, A., Moore, M., Beattie, A., McLaren, D. A., Finlayson, M., ibid. 6. Stewart, G. T. ibid. p. 983. 7. Moore, M. R., Meredith, P. A., Goldberg, A. ibid. 1977, i, 717. 8 David, O., Hoffman, S., McGann, B., Sverd, J., Clark, J. ibid. 1976, ii, 1376.
366
with absent data on, for example, prenatal and perinatal factors, selectively to the aetiology-unknown group, instead of their being analysed as a separate group. The effects on the findings of including these children in the aetiology-unknown group cannot be assessed. The second group of studies is headed by that of LANSDOWN and co-workers,9 who investigated blood-lead levels of schoolchildren living near a smelting works in London, England, and linked these with measurements of intelligence, reading attainments, and behaviour in the same children. A house-to-house search by health visitors identified 275 children aged between 6 and 17 living within 500 m of the smelter. Of these, over three-quarters had blood taken and the other tests performed. Higher blood-levels were found in children living within 400 m of the factory than in those living 400-500 m away. Tests of intelligence and behaviour, however, showed no difference between children with high or low blood-lead levels. Children who had lived in the least contaminated area (i.e., over 500 m from the smelter) during their first 2 years tended to be less intelligent, more overactive, and more disturbed than those living closer. LANSDOWN and his colleagues concluded that mild exposure to lead does not lead to adverse subclinical mental effects. The absence of bloodlead estimations in 22% of the children may have biased the findings. The relevance of current bloodlead concentrations to early childhood lead exposure was questioned in subsequent correspondence, as were the possible biases in the use of teachers’ assessment of behaviour, and of the influence upon behaviour and educational attainment of differences in social and family composition of the population at increasing distance from the factory site.lO,12 This last point prompted HEBEL, KINCH, and ARMSTRONG13 to perform a study in Birmingham, England, that allowed for factors related to distance from factory. They recorded the scores in the "eleven-plus" examination for 851 children who had lived since birth in a high-lead-polluted area close to a battery factory, and for 1642 children in two similar but low-lead or unpolluted control areas. The eleven-plus examination scores were higher among children living in the high-leadpolluted communities than in the low and unpolluted areas. This difference persisted when adjustments were made for social class, birth rank, and maternal age. While concluding that their observations supported the contention that environmental lead pollution of the degree found in Birmingham does not produce an overall deficiency in school 9
performance, HEBEL and others nevertheless believe that their findings may not be completely reliable. They note that, with the numbers studied, a deficit of 5% or so in eleven-plus score could have been missed between the children living close to the factory and those further away. The population defined as all those who were resident in the areas at the time of the eleven-plus examination, and, as with the London study, differential outmigration may have biased the findings. LANDRIGAN and co-workers14 studied children aged 3-15 who had lived for at least twelve of the preceding twenty-four months within 6-6 km of a lead smelter in El Paso, Texas. They identified 46 children with blood-lead levels of 40-80 g/dl. A control group of 78 children with blood-lead levels of less than 40 fl-g/dl were chosen so that, as a group, they matched the high-blood-lead group in respect of age, sex, socioeconomic status, language spoken at home, and length of time and situation in the area. Examiners, who did not know to which group the child belonged, made various neurowas
psychological assessments. Age-adjusted i.Q. performance proved to be significantly decreased in the high-blood-lead group, as was the finger-wrist tapping test. Full-scale i.Q., verbal i.Q., and behaviour and hyperactivity ratings did not suffer. LANDRIGAN and others were careful to point out that the group-matching procedure was not wholly satisfactory since the control group was older and contained a lower proportion of boys than the highlead group. However, differences between the groups persisted when the i.Q. scores were adjusted for age and stratified by sex; likewise, stratification of finger-tapping results by age and sex did not alter the relationship. These workers concluded that blood-lead levels of 50 µg/dl and over may result in subtle yet statistically significant impairments of fine motor skills and intelligence. What can we conclude? The methodological problems with the two case-control studies are such that the findings must be viewed with caution. The prevalence studies have concentrated upon supposedly normal schoolchildren. The methodological problems are by no means so serious, but the investigators depended on detection of minor differences in intelligence, behaviour, educational attainment, and neurological function. None of the measurement techniques used may be sufficiently sensitive for this purpose. As with the case-control studies it proved difficult to allow for the known factors that can influence children’s mental attainments. The message is now clear, if unwelcome: there is no easy way to find out whether lead, at the exposures studied, causes mental handicap or minor intellectual
Lansdown, R. G., Shepherd, J., Clayton, B. E , Delves, H. T., Graham, P. J. Turner, W. C. ibid 1974, i, 538.
10. David, O. J. ibid. p 866. 11. Bryce-Smith, D., Waldron, H. A ibid. p 1166. 12. Landrigan, P. J, Whitworth, R. H , Baloh, R. W. ibid. p. 1167. 13 Hebel, J. R , Kinch, D., Armstrong, E. Br. J. prev. soc. Med.
14. Landrigan, P. J., Whitworth, 1976, 30, 170.
W. F.,
R. H., Baloh, R. W., Staehling, N. W., Barthel, Rosenblum, B. F. Lancet, 1975, i, 708.
367
impairment, or any damage at all. Follow-up of pregnant women with high and low lead exposure and subsequent assessment of the mental attainments of their offspring seems the next step; but there may be difficulties in obtaining adequate numbers and in allowing for the effects of other factors on mental attainment.
THE SUPPLIANT SPLEEN
"A STRANGE sense of complacency pervades the surgical scene in the matter of operative injury to the spleen."’ Operating in the left upper quadrant of the abdomen, the surgeon has been taught (or has learnt by osmosis from his seniors) that splenectomy because of accidental trauma is just one of those things and without detriment to the patient. So strongly is this view part of our inbuilt surgical attitudes that "accidental" splenectomy can account for between a fifth and a quarter of all spleens submitted for pathological examination.2 From this must be excluded those organs removed as part of a radical block dissection for cancer of the stomach; however questionable as a method of enhancing the possibility of cure of this disease, such splenectomy is deliberate rather than accidental. There are two classes of hazards in all splenectomies which should give the surgeon pause before he plies his knife. The one is anatomical; the other more subtle and immunological. The anatomy of the spleen and its adjacent organs3 has been described often, but perhaps not often enough. There are three salient points. First, omental adhesions to the lower pole, which are so frequent as to be normal and which can be torn with ease even during a simple exploration of the upper abdomen. Second, the small amount of room between the lienorenal ligament and the upper part of the greater curvature, so that the most proximal short gastric vessels have a length of only a centimetre or so and manipulations to the left of the œsophagus—as in most forms of vagotomy-put the splenic capsule at risk. These are the causes of capsular tears which lead to splenectomy. Third, and the hazard underlying it, is the proximity of the pancreatic tail to the hilum which renders the pancreas liable to damage if the splenic vessels are not carefully dissected and ligated. Though injury to the pancreas is totally avoidable, the surgeon who has embarked on splenectomy for tiresome capsular bleeding at the end of a tedious procedure on the stomach may be technically below his best; if the pancreas is damaged the worst result is a spreading pancreatitis, the best a left-
upper-quadrant pseudocyst. As important as the operative complications, if not more so, are the long-term sequelæ of splenectomy. Again the surgeon, satisfied with having saved life in the dramatic circumstances of trauma, pleased with his contribution to therapy (as in haemolytic anaemia or thrombocytopenic purpura), or happy to act out his role as a technician in relation to the staging of lymphoma, may easily forget about the more subtle effects of the organ
he has produced. Yet since 1950 splenechas known to alter host resistance to infecbeen tomy tion, mainly though not exclusively in the young. In American servicemen splenectomised for trauma, Robinette and Fraumeni4 recorded an increased deathrate, specifically from ischwmic heart-disease and pneumonia. The first could be due to post-splenectomy thrombocytosis, which can persist for years; the second has lately been given a firmer immunological base. Sullivan and his colleagues report diminished responses in response to challenge with specific antigens-those of bacteriophage and pneumococcal capsule-in asplenic man. Intravenously administered phage antigen is responded to only in a blunted way, and a secondary challenge is not associated with the usual switch from production of IgG to that of IgM. Intravenous capsular antigens do not yield an antibody response though in "normal" post-splenectomy man subcutaneous antigens do. Finally, in patients with Hodgkin’s disease who are both asplenic and have received heavy irradiation or other forms of immunosuppression, subcutaneous administration leads to a poor or absent response. The immunological systems analyst can interpret these results as suggesting that, although the spleen is the primary way-station for blood-borne antigens in the complex processes which initiate the production of antibody, either to bacteriophage or to capsular antigen, for capsular antigen other healthy lymphoid tissue will do provided the antigen traverses it. The doctor charged with care of splenectomised patients learns that he can protect his patient against one of the commonest overwhelming infections-that with Streptococcus pneumoniœ—by subcutaneous injection of antigen; but, as Sullivan and his colleagues point out, if the patient has Hodgkin’s disease, such immunisation must precede further attacks on the regional lymph-node mass. Finally, what of the surgeon? As he explores and operates in the left upper quadrant, he might well have floating in front of his eyes a vision of the spleen pleading with him to avoid injury. Nevertheless, damage will inevitably sometimes happen. Does this mean splenectomy ? In the past it nearly always has, because, despite
deprivation
lacerations (often quite small) continue to bleed. Lately, however, Morgenstern’ has shown that topical hæmostasis can be achieved with fibrillary collagen; in 21 consecutive patients he has avoided splenectomy, without important complications. Here is a new technique which, if equally effective in other hands, we should certainly be trying.
packing, capsular
CYPROHEPTADINE CYPROHEPTADINE is a potent antagonist of histamine, acetylcholine and serotonin.6 As an antihistamine it has proved disappointing in allergic disorders but its antiserotonin properties are now attracting much interest. During evaluation of its antihistamine effect in childhood asthma an incidental increase in appetite and weight was noticed and in a subsequent controlled trial weight-gain was found to be consistently greater with cyproheptadine than with chlorpheniramine, although Robinette, C. D., Fraumeni, J. F. Lancet, 1977, ii, 127. Sullivan, J. L., Ochs, H. D., Schiffman, G., Hammerschlag, M., Miser, J., Vichinsky, E., Wedgwood, R. J. ibid. Jan.28, 1978, p. 178. 6. Stone, C. A., Wenger, W. E., Ludden, C. T. J. Pharmac. exp. Ther. 1961, 131, 73.
4. 5. 1. Morgenstern, L. Surgery Gynec. Obstet. 1977, 145, 525. 2. Quan, S., Castleman, B. New Engl. J. Med. 1949, 240, 835. 3. Lord, M. D., Gourevitch, A. Br. J. Surg. 1965, 52, 202.
THE LANCET
Lead and Mental Handicap of mental handicap in children are known, there remains a group of children in whom the aetiology is obscure. It is in this group that toxic chemicals, such as lead, could be a factor. Heavy intoxication by inorganic lead is a long-known cause of severe neurological and psychological disorders in children. Could exposure to lower amounts of inorganic lead, at times when the nervous system may be especially susceptible, during prenatal life and early childhood, result in mental handicap? In 1973 we found the evidence on subclinical lead poisoning inconclusive.’ What has happened since then, and are we any nearer a firm conclusion on the role of inorganic lead in mental handicap? The epidemiological studies published since then fall into two main groups-investigations of the lead exposure of children already diagnosed as mentally handicapped; and studies of the intelligence of schoolchildren exposed to different levels of environmental lead. In 1975 BEATTIE and co-workers2 reported a case-control study of mentally retarded children in Glasgow, a city that still had lead water-pipes in many of its older properties. Because the Glasgow water is plumbosolvent domestic drinking-water may contain large amounts of lead. 77 mentally retarded children aged 2-5, in whom no specific factor had been incriminated, formed the cases. A control group of 77 children was drawn from nonmentally-retarded healthy children matched for age, sex, and geographic location. No details are given on the source of these controls or on the methods of selection before matching. Home addresses during each child’s first year of life and the relevant pregnancy were obtained and a sample ALTHOUGH
some causes
1. Lancet, 1973, i, 87. 2. Beattie, A. D., Moore, M. R., Goldberg, A., Finlayson, M. J. W., Graham, J F., Mackie, E. M., Main, J. C., McLaren, D. A., Murdoch, R. M., Stewart, G. T., ibid. 1975, i, 589.
of water was taken from the kitchen cold-water tap at each address, where this was possible. in 13 of the 77 case-control pairs data on home water-lead levels were not available for one member of the pair. The mean water-lead levels in each trimester of pregnancy and in the first and second six months of life were consistently higher in the group of mentally retarded children than in the controls. BEATTIE and his colleagues concluded that the results strongly suggested that lead exposure causes mental retardation. This study attracted critical comment, mainly on the methodology. Specifically, the adequacy of the matching process used for the controls was questioned.3,4 A major objection, which the Glasgow workers themselves recognised,s,6 was their inability to include matching variables, such as maternal age and birth order, that may be relevant to the development of mental retardation. In another investigation the Glasgow group measured the lead in blood previously collected from the same children (for phenylketonuria screening) in the first two weeks of life. Blood-samples were found for 41 of the 77 mentally retarded children and 36 of the 77 controls, yielding only 24 matched pairs where both members had blood-samples, The distribution of blood-lead levels showed a trend towards higher levels in the mentally retarded group. The absence of blood-lead data on 77 out of 154 children means that any conclusions should be cautious ones. In a case-control study from New York, bloodleads were compared in three groups of 4-12-yearolds. The cases consisted of 64 mentally retarded children; 33 had no known cause for retardation while 31 had a "probable" cause. These children all had i.Q.s between 55 and 84 and had attended a clinic for the diagnosis and treatment of retardation. (Blood-lead analyses had been done routinely on all.) A control group of 30 children was drawn from a general pxdiatric outpatient clinic, such that they were within the same age-range, had a sex ratio comparable to that of the other group, and were not too ill to participate. Mean blood-lead levels were highest in the mentally retarded group with xtiology unknown; there was little difference in blood-lead between the controls and the mentally retarded children with probable xtiology. With no more than 33 children in each group, this is a rather small study and doubts must arise on how representative the findings are, expecially in respect of the controls. Biases may have been introduced by classification of those retarded children
3. Heasman, M. A. ibid. p. 982. 4. Primrose, D. A. ibid. 5. Goldberg, A., Moore, M., Beattie, A., McLaren, D. A., Finlayson, M., ibid. 6. Stewart, G. T. ibid. p. 983. 7. Moore, M. R., Meredith, P. A., Goldberg, A. ibid. 1977, i, 717. 8 David, O., Hoffman, S., McGann, B., Sverd, J., Clark, J. ibid. 1976, ii, 1376.
366
with absent data on, for example, prenatal and perinatal factors, selectively to the aetiology-unknown group, instead of their being analysed as a separate group. The effects on the findings of including these children in the aetiology-unknown group cannot be assessed. The second group of studies is headed by that of LANSDOWN and co-workers,9 who investigated blood-lead levels of schoolchildren living near a smelting works in London, England, and linked these with measurements of intelligence, reading attainments, and behaviour in the same children. A house-to-house search by health visitors identified 275 children aged between 6 and 17 living within 500 m of the smelter. Of these, over three-quarters had blood taken and the other tests performed. Higher blood-levels were found in children living within 400 m of the factory than in those living 400-500 m away. Tests of intelligence and behaviour, however, showed no difference between children with high or low blood-lead levels. Children who had lived in the least contaminated area (i.e., over 500 m from the smelter) during their first 2 years tended to be less intelligent, more overactive, and more disturbed than those living closer. LANSDOWN and his colleagues concluded that mild exposure to lead does not lead to adverse subclinical mental effects. The absence of bloodlead estimations in 22% of the children may have biased the findings. The relevance of current bloodlead concentrations to early childhood lead exposure was questioned in subsequent correspondence, as were the possible biases in the use of teachers’ assessment of behaviour, and of the influence upon behaviour and educational attainment of differences in social and family composition of the population at increasing distance from the factory site.lO,12 This last point prompted HEBEL, KINCH, and ARMSTRONG13 to perform a study in Birmingham, England, that allowed for factors related to distance from factory. They recorded the scores in the "eleven-plus" examination for 851 children who had lived since birth in a high-lead-polluted area close to a battery factory, and for 1642 children in two similar but low-lead or unpolluted control areas. The eleven-plus examination scores were higher among children living in the high-leadpolluted communities than in the low and unpolluted areas. This difference persisted when adjustments were made for social class, birth rank, and maternal age. While concluding that their observations supported the contention that environmental lead pollution of the degree found in Birmingham does not produce an overall deficiency in school 9
performance, HEBEL and others nevertheless believe that their findings may not be completely reliable. They note that, with the numbers studied, a deficit of 5% or so in eleven-plus score could have been missed between the children living close to the factory and those further away. The population defined as all those who were resident in the areas at the time of the eleven-plus examination, and, as with the London study, differential outmigration may have biased the findings. LANDRIGAN and co-workers14 studied children aged 3-15 who had lived for at least twelve of the preceding twenty-four months within 6-6 km of a lead smelter in El Paso, Texas. They identified 46 children with blood-lead levels of 40-80 g/dl. A control group of 78 children with blood-lead levels of less than 40 fl-g/dl were chosen so that, as a group, they matched the high-blood-lead group in respect of age, sex, socioeconomic status, language spoken at home, and length of time and situation in the area. Examiners, who did not know to which group the child belonged, made various neurowas
psychological assessments. Age-adjusted i.Q. performance proved to be significantly decreased in the high-blood-lead group, as was the finger-wrist tapping test. Full-scale i.Q., verbal i.Q., and behaviour and hyperactivity ratings did not suffer. LANDRIGAN and others were careful to point out that the group-matching procedure was not wholly satisfactory since the control group was older and contained a lower proportion of boys than the highlead group. However, differences between the groups persisted when the i.Q. scores were adjusted for age and stratified by sex; likewise, stratification of finger-tapping results by age and sex did not alter the relationship. These workers concluded that blood-lead levels of 50 µg/dl and over may result in subtle yet statistically significant impairments of fine motor skills and intelligence. What can we conclude? The methodological problems with the two case-control studies are such that the findings must be viewed with caution. The prevalence studies have concentrated upon supposedly normal schoolchildren. The methodological problems are by no means so serious, but the investigators depended on detection of minor differences in intelligence, behaviour, educational attainment, and neurological function. None of the measurement techniques used may be sufficiently sensitive for this purpose. As with the case-control studies it proved difficult to allow for the known factors that can influence children’s mental attainments. The message is now clear, if unwelcome: there is no easy way to find out whether lead, at the exposures studied, causes mental handicap or minor intellectual
Lansdown, R. G., Shepherd, J., Clayton, B. E , Delves, H. T., Graham, P. J. Turner, W. C. ibid 1974, i, 538.
10. David, O. J. ibid. p 866. 11. Bryce-Smith, D., Waldron, H. A ibid. p 1166. 12. Landrigan, P. J, Whitworth, R. H , Baloh, R. W. ibid. p. 1167. 13 Hebel, J. R , Kinch, D., Armstrong, E. Br. J. prev. soc. Med.
14. Landrigan, P. J., Whitworth, 1976, 30, 170.
W. F.,
R. H., Baloh, R. W., Staehling, N. W., Barthel, Rosenblum, B. F. Lancet, 1975, i, 708.
367
impairment, or any damage at all. Follow-up of pregnant women with high and low lead exposure and subsequent assessment of the mental attainments of their offspring seems the next step; but there may be difficulties in obtaining adequate numbers and in allowing for the effects of other factors on mental attainment.
THE SUPPLIANT SPLEEN
"A STRANGE sense of complacency pervades the surgical scene in the matter of operative injury to the spleen."’ Operating in the left upper quadrant of the abdomen, the surgeon has been taught (or has learnt by osmosis from his seniors) that splenectomy because of accidental trauma is just one of those things and without detriment to the patient. So strongly is this view part of our inbuilt surgical attitudes that "accidental" splenectomy can account for between a fifth and a quarter of all spleens submitted for pathological examination.2 From this must be excluded those organs removed as part of a radical block dissection for cancer of the stomach; however questionable as a method of enhancing the possibility of cure of this disease, such splenectomy is deliberate rather than accidental. There are two classes of hazards in all splenectomies which should give the surgeon pause before he plies his knife. The one is anatomical; the other more subtle and immunological. The anatomy of the spleen and its adjacent organs3 has been described often, but perhaps not often enough. There are three salient points. First, omental adhesions to the lower pole, which are so frequent as to be normal and which can be torn with ease even during a simple exploration of the upper abdomen. Second, the small amount of room between the lienorenal ligament and the upper part of the greater curvature, so that the most proximal short gastric vessels have a length of only a centimetre or so and manipulations to the left of the œsophagus—as in most forms of vagotomy-put the splenic capsule at risk. These are the causes of capsular tears which lead to splenectomy. Third, and the hazard underlying it, is the proximity of the pancreatic tail to the hilum which renders the pancreas liable to damage if the splenic vessels are not carefully dissected and ligated. Though injury to the pancreas is totally avoidable, the surgeon who has embarked on splenectomy for tiresome capsular bleeding at the end of a tedious procedure on the stomach may be technically below his best; if the pancreas is damaged the worst result is a spreading pancreatitis, the best a left-
upper-quadrant pseudocyst. As important as the operative complications, if not more so, are the long-term sequelæ of splenectomy. Again the surgeon, satisfied with having saved life in the dramatic circumstances of trauma, pleased with his contribution to therapy (as in haemolytic anaemia or thrombocytopenic purpura), or happy to act out his role as a technician in relation to the staging of lymphoma, may easily forget about the more subtle effects of the organ
he has produced. Yet since 1950 splenechas known to alter host resistance to infecbeen tomy tion, mainly though not exclusively in the young. In American servicemen splenectomised for trauma, Robinette and Fraumeni4 recorded an increased deathrate, specifically from ischwmic heart-disease and pneumonia. The first could be due to post-splenectomy thrombocytosis, which can persist for years; the second has lately been given a firmer immunological base. Sullivan and his colleagues report diminished responses in response to challenge with specific antigens-those of bacteriophage and pneumococcal capsule-in asplenic man. Intravenously administered phage antigen is responded to only in a blunted way, and a secondary challenge is not associated with the usual switch from production of IgG to that of IgM. Intravenous capsular antigens do not yield an antibody response though in "normal" post-splenectomy man subcutaneous antigens do. Finally, in patients with Hodgkin’s disease who are both asplenic and have received heavy irradiation or other forms of immunosuppression, subcutaneous administration leads to a poor or absent response. The immunological systems analyst can interpret these results as suggesting that, although the spleen is the primary way-station for blood-borne antigens in the complex processes which initiate the production of antibody, either to bacteriophage or to capsular antigen, for capsular antigen other healthy lymphoid tissue will do provided the antigen traverses it. The doctor charged with care of splenectomised patients learns that he can protect his patient against one of the commonest overwhelming infections-that with Streptococcus pneumoniœ—by subcutaneous injection of antigen; but, as Sullivan and his colleagues point out, if the patient has Hodgkin’s disease, such immunisation must precede further attacks on the regional lymph-node mass. Finally, what of the surgeon? As he explores and operates in the left upper quadrant, he might well have floating in front of his eyes a vision of the spleen pleading with him to avoid injury. Nevertheless, damage will inevitably sometimes happen. Does this mean splenectomy ? In the past it nearly always has, because, despite
deprivation
lacerations (often quite small) continue to bleed. Lately, however, Morgenstern’ has shown that topical hæmostasis can be achieved with fibrillary collagen; in 21 consecutive patients he has avoided splenectomy, without important complications. Here is a new technique which, if equally effective in other hands, we should certainly be trying.
packing, capsular
CYPROHEPTADINE CYPROHEPTADINE is a potent antagonist of histamine, acetylcholine and serotonin.6 As an antihistamine it has proved disappointing in allergic disorders but its antiserotonin properties are now attracting much interest. During evaluation of its antihistamine effect in childhood asthma an incidental increase in appetite and weight was noticed and in a subsequent controlled trial weight-gain was found to be consistently greater with cyproheptadine than with chlorpheniramine, although Robinette, C. D., Fraumeni, J. F. Lancet, 1977, ii, 127. Sullivan, J. L., Ochs, H. D., Schiffman, G., Hammerschlag, M., Miser, J., Vichinsky, E., Wedgwood, R. J. ibid. Jan.28, 1978, p. 178. 6. Stone, C. A., Wenger, W. E., Ludden, C. T. J. Pharmac. exp. Ther. 1961, 131, 73.
4. 5. 1. Morgenstern, L. Surgery Gynec. Obstet. 1977, 145, 525. 2. Quan, S., Castleman, B. New Engl. J. Med. 1949, 240, 835. 3. Lord, M. D., Gourevitch, A. Br. J. Surg. 1965, 52, 202.