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LACTOSE INTOLERANCE IN GREEKS
367
Letters to the Editor MEDICAL RESEARCH IN EUROPE
SiR,-All will applaud your timely article (Jan. 27, p. 189) country’s part in the European Community’s medical research programme. Particularly noteworthy are the statements : availability of people with originality and quality " and provision... for all the Community’s talented people on this
"
"
to
carry their ideas to fruition". In these remarks you
pinpoint the essence of the matter-people of originality and sponsorship of their efforts. Originality and creativity can often exist outside formal research. Old Russell working away in his retirement succeeded by systematic creative effort in producing the Russell lupin that lights up the sombre lives of many. His
Of the 250 subjects examined, 58 (32 males, 26 females) (23%) showed a flat lactose-tolerance curve (L.T.c.). 155 were drinking at least half a pint of milk daily. 45 with a flat L.T.c. and 18 with a normal L.T.C. reported symptoms after ingestion of milk. On the other hand, all subjects with a flat L.T.c. and 22 with a normal L.T.C. reported symptoms during the test. Of the 24 patients with an irritable-colon syndrome, as many as 17 (71%) had a flat L.T.C.
These results differ
considerably from those previously reported, perhaps partly because earlier workers tested fewer subjects and partly owing to a different pattern of lactose tolerance among Greek populations of various areas. We are extending this work, and are measuring lactose activity in the small-intestinal mucosa. Professorial Medical Unit, Athens Medical School,
creativity was not within a formal research service. Similarly creativity can arise spontaneously anywhere within the health service. To achieve provision for creativity we must go far beyond our facilities for formal research by foundations, universities, &c., valuable and essential though such institutions are. Indeed, the recent replanning of formal research on a customer/contractor principle is a step forward in the organisation of identified research. But nevertheless this approach must be limited, for creativity often arises outside the formal research organisation. An establishment is laudable and necessary to maintain what has been achieved. But originality must go beyond and is the antithesis of established opinion. To discover, sponsor, and develop creative research whenever it arises is as important as formal research. This is why I suggestedthe formation of departments of creative development, probably at a regional or possibly departmental level. These departments would sponsor creativity, and that they would not be retarded by established opinion in our field could be guaranteed by their committees being drawn from original minds in other fields. Europe can only benefit from such an innovation within our health service. Institute of Family Psychiatry, Ipswich Hospital, Ipswich IP1 3TF.
JOHN G. HOWELLS.
LACTOSE INTOLERANCE IN GREEKS
SIR,-Spanidou and Petrakis2 have reported from San Francisco that of 16 Greek (non-Cypriot) students in the U.S.A., 6 (38%) had primary lactose intolerance, compared with none of 13 U.S. Americans of Northern European backgrounds. The question of an exceptionally high prevalence of lactose intolerance-the highest among European ethnic groups-in Greeks was raised by the work of awl. and of Neale.44 Since 1970 we have studied in this hospital ’140 males and 110 females, aged 15-78 years, all inpatients in general medical wards. 24 of the subjects studied had a spastic or irritable colon syndrome. To test lactose intolerance 50 g. of glucose-free lactose, diluted in 300 ml. of water, was administered to each fasting subject. Capillary blood samples were taken from the fingertip before ingestion of lactose and 15, 30, 60, 90, and 150 minutes after. Blood-glucose was estimated by the glucose-oxidase method. A rise in blood-glucose of 20 mg. per 100 ml. or more above fasting levels was considered as normal.
McMichael
et
1. 2.
Lancet, 1972, ii, 324. Spanidou, E. P., Petrakis, N. L. ibid. p. 872. 3. McMichael, H. B., Webb, J., Dawson, A. M. Br. med. J. 1966, ii, 1037.
4.
Neale, G. Proc. R. Soc. Med. 1968, 61, 1099.
Evangelismos Hospital, Athens 140, Greece.
N. ZOGRAFOS T. KANAGHINIS I. HATZIOANNOU C. GARDIKAS.
SIR,-We were very interested in the report by Spanidou and Petrakis1 pointing to a greater prevalence of lactose intolerance in 16 Greek students than in 13 Americans of northern European extraction, and to discrepancies between individuals with lactose intolerance and those with symptoms after milk-drinking. Several years ago McMichael et a1.2 and Neale3 suggested that the frequency of lactose intolerance may vary in different segments of the Greek population. We report here our findings in 82 healthy Greek children, aged 1-13 years. Lactose tolerance was tested in these healthy children in an attempt to evaluate its validity for the diagnosis of primary and secondary lactase deficiency in infants and children with chronic diarrhoea. The group consisted of 52 healthy boys and 30 girls with no clinical symptoms on ingestion of normal quantities of milk (200-500 ml. daily). They were given 2 g. per kg. bodyweight of glucose-free lactose, suspended as a 10% solution in tap-water. Venous blood samples, usually in duplicate, were drawn just before lactose ingestion and 30, 60, 90, and 120 minutes later. Blood-glucose was estimated by the glucose-oxidase method.4A child was regarded as lactosetolerant if the blood-glucose rose by more than 20 mg. per 100 ml. above fasting levels within 60 minutes of lactose
ingestion. A maximum increase of glucose by more than 20 mg. per 100 ml. was observed in 27 children (33%). The remaining 55 (67%) were by definition lactose-intolerant; in these children the rise of glucose levels varied widely. It is of particular interest that, of 55 lactose-intolerant children, in 22 (40%) glucose levels following ingestion of lactose were lower than fasting levels and all but 4 experienced symptoms (mainly abdominal distension and pain, and diarrhoea) after lactose ingestion. On the contrary, of the remaining 33 children in whom glucose levels rose by 2-20 mg. per 100 ml. only 4 had symptoms. None of the lactose-tolerant children had symptoms after ingesting lactose. These findings contrast with those of Spanidou and Petrakis; in our group, symptoms were experienced mainly by children in whom the lactose-tolerance test was grossly abnormal. This may be explained by the fact that these children can tolerate well the rather low total lactose content of the daily intake of milk but not the huge amount administered in the oral test. This confirms the clinical 1. 2.
Spanidou, E. P., Petrakis, N. L. Lancet, 1972, ii, 872. McMichael, H. B., Webb, J., Dawson, A. M. Br. med. J. 1966, ii,
3. 4.
Neale, G. Proc. R. Soc. Med. 1968, 61, 1099. Huggett, A: St. G., Nixon, D. A. Lancet, 1957, ii, 368.
1037.
368 that milk intolerance among Greek children is If there were any correlation between milk intolerance and the results of the lactose-tolerance test, many infants and younger children fed with sufficient quantities of milk might be expected to have severe disorders. Our findings, which are similar to those reported in a small number of Greek adults,indicate that the lactosetolerance test is abnormal in a high proportion of normal Greek children who have no symptoms after drinking normal quantities of milk. Whatever the explanation of this discrepancy may be, it is evident that the lactose-tolerance test is of little value in the diagnosis of primary or secondary lactose deficiency, at least in Greek infants and children.
impression
not common.
Department of Pædiatrics, Athens University, St. Sophie’s Children’s Hospital, Athens 608, Greece.
CHRISTOS KATTAMIS KALIOPI ANASTASSEAVLACHOU NICOLAS LOGOTHETIS VASILIKI SIRIOPOULOU NICOLAS MATSANIOTIS.
ROSETTE SEDIMENTATION FOR SEPARATION OF HUMAN T AND B CELLS SIR,-We were interested in the claim of Dr Wybran and his colleagues (Jan. 20, p. 126) that they have isolated normal T cells in chronic lymphatic leukaemia (C.L.L.). Although we have no information on C.L.L. we have been using a very similar method to fractionate the peripheral lymphocytes of normals and of patients with immunological defects. We have concluded that the lymphocytes which pass through the gradient together with sheep red blood-cells are a distinct subpopulation of T cells.I The lymphocytes which remain at the interface seem to consist of B cells together with a third population which may or may not be
wholly T cells. The principle of the method used by Dr Wybran and his associates and by ourselves is that lymphocytes which form rosettes (R.F.C.) will sediment, leaving non-R.F.c. at the interface. Different authors have found that between 4% and 81% of lymphocytes are R.F.c. In their recent work Wybran et al. claimed that approximately 67% of normal peripheral lymphocytes are R.F.c., but earlier reported a range of 4-40%. Unfortunately, they do not explain the rather dramatic increase and the increment may be at the cost of specificity. Our own experience and that of most others is more in line with the earlier report. Wybran et al. have found that after rosette sedimentation approximately 97% of the pellet cells were R.F.c., but so were 38% of the interface cells. Our own values are 27% and 0-6%, respectively, with the pellet cells accounting for between 10 and 30% of the peripheral lymphocytes layered into the gradient. We have therefore concluded that we have separated a subpopulation of T cells which form firm but transient rosettes. Wybran et al. do not indicate the proportion of the initial cells which reach the pellet and do not explain the apparently excessive number of R.F.c. which remain at the interface. Finally, Wybran et al. draw attention to the relatively high rate of spontaneous D.N.A. synthesis of the interface cells. Our own data (in preparation) are more notable for the low rate of synthesis of the pellet cells, and it is interesting that table 11 of Wybran et al. confirms our finding. We suggest that there may be a spectrum of rosette-forming capacity and that " tight R.F.C." are T cells with a low rate of D.N.A. synthesis. " Loose x..c." may be a more rapidly dividing T-cell subpopulation. Thus, D.N.A. synthesis and rosette-forming capacity could be 1.
Zilko, P. J., Dawkins, R. L. Unpublished.
inversely related, perhaps because rosette formation does not occur equally during the different phases of the cell cycle. At the very least, possibilities such as these suggest that it may be unwise to imply that the T cells which Wybran et al. claim to have separated are a homogeneous population. It may also be premature to state that normal T cells have been isolated in c.L.L. without indicating that different subpopulations should be considered. Department of Pathology, University of Western Australia, Perth, Western Australia 6000.
R. L. DAWKINS P. J. ZILKO.
RESUSCITATION AFTER ELECTRIC SHOCK
SIR9 The recommendations of Morley and CarterI referred to in your editorial of Feb. 3 (p. 244) are naturally of great interest to us, especially the reported high primary cardiac death-rate and the recommendation for two " thumps ". With this the Joint Manual almost entirely agrees, except that we are prepared to go up to ten. The suggestion that Holger Nielsen or Schafer, by virtue of movement of the limbs, has a beneficial cardiac as well as respiratory effect is very interesting. We think this may well be due to increased venous pressure acting as a stimulus in much the same manner that raising the legs may restart an arrested heart. The manual does in fact include Holger Nielsen (better than Schafer), although not for the reasons suggested by Morley and Carter, and our people are trained in it as an alternative to mouth-tomouth, which remains the most effective from a purely
respiratory standpoint. The other points raised in your last paragraph concerning training are important, and will certainly be considered when we come to produce the next edition. H. C.
STEWART,
Chief Medical Officer, St. John Ambulance Association.
H.Q. St. John Ambulance, 1 Grosvenor Crescent, London SW1.
ROBERT OLLERENSHAW, Surgeon-in-Chief, St. John Ambulance Brigade.
PREGNANCY IN WOMAN WITH MENINGOMYELOCELE SIR,-In response to the letter by Dr Fujimoto and his colleagues (Jan. 13, p. 104), I should like to report the
following
case.
A 35-year-old woman with a small lumbar meningomyelocele and mild paresis of the lower extremities was married at the age of 22. A year later she was delivered, at term, of a stillborn male infant with meningomyelocele, hydrocephalus, and a bilateral club-foot deformity. A therapeutic abortion was performed 10 years later when she became pregnant for the second time. At the age of 35 she became pregnant for the third time and was referred for genetic counselling. Her husband’s health, physical condition, and family history were unremarkable. A review of the patient’s family history showed that she had two normal siblings and two normal nephews; one sister who was otherwise normal died at 5 years during the 1939-45 war. In addition, she had had a sister who died at the age of 20 years of complications of a meningomyelocele. In 1966, when the couple were seen for genetic counselling, no similar case had been published and her genetic risk was not clear to me. They wanted a normal child very badly, but were " unwilling to continue the pregnancy if there was a significant chance that the baby might be born with a meningomyelocele. During a telephone call to Great Ormond Street, Dr Cedric Carter stated that the risk of fetal defect was about the same as for the case of normal parents who had had two affected infants to date. That risk he judged to be 1 in 7. This risk figure was unacceptable to the woman, so the "
1.
Morley, R., Carter, A. O. Archs envir. Hlth, 1972, 25, 276.
Letters to the Editor MEDICAL RESEARCH IN EUROPE
SiR,-All will applaud your timely article (Jan. 27, p. 189) country’s part in the European Community’s medical research programme. Particularly noteworthy are the statements : availability of people with originality and quality " and provision... for all the Community’s talented people on this
"
"
to
carry their ideas to fruition". In these remarks you
pinpoint the essence of the matter-people of originality and sponsorship of their efforts. Originality and creativity can often exist outside formal research. Old Russell working away in his retirement succeeded by systematic creative effort in producing the Russell lupin that lights up the sombre lives of many. His
Of the 250 subjects examined, 58 (32 males, 26 females) (23%) showed a flat lactose-tolerance curve (L.T.c.). 155 were drinking at least half a pint of milk daily. 45 with a flat L.T.c. and 18 with a normal L.T.C. reported symptoms after ingestion of milk. On the other hand, all subjects with a flat L.T.c. and 22 with a normal L.T.C. reported symptoms during the test. Of the 24 patients with an irritable-colon syndrome, as many as 17 (71%) had a flat L.T.C.
These results differ
considerably from those previously reported, perhaps partly because earlier workers tested fewer subjects and partly owing to a different pattern of lactose tolerance among Greek populations of various areas. We are extending this work, and are measuring lactose activity in the small-intestinal mucosa. Professorial Medical Unit, Athens Medical School,
creativity was not within a formal research service. Similarly creativity can arise spontaneously anywhere within the health service. To achieve provision for creativity we must go far beyond our facilities for formal research by foundations, universities, &c., valuable and essential though such institutions are. Indeed, the recent replanning of formal research on a customer/contractor principle is a step forward in the organisation of identified research. But nevertheless this approach must be limited, for creativity often arises outside the formal research organisation. An establishment is laudable and necessary to maintain what has been achieved. But originality must go beyond and is the antithesis of established opinion. To discover, sponsor, and develop creative research whenever it arises is as important as formal research. This is why I suggestedthe formation of departments of creative development, probably at a regional or possibly departmental level. These departments would sponsor creativity, and that they would not be retarded by established opinion in our field could be guaranteed by their committees being drawn from original minds in other fields. Europe can only benefit from such an innovation within our health service. Institute of Family Psychiatry, Ipswich Hospital, Ipswich IP1 3TF.
JOHN G. HOWELLS.
LACTOSE INTOLERANCE IN GREEKS
SIR,-Spanidou and Petrakis2 have reported from San Francisco that of 16 Greek (non-Cypriot) students in the U.S.A., 6 (38%) had primary lactose intolerance, compared with none of 13 U.S. Americans of Northern European backgrounds. The question of an exceptionally high prevalence of lactose intolerance-the highest among European ethnic groups-in Greeks was raised by the work of awl. and of Neale.44 Since 1970 we have studied in this hospital ’140 males and 110 females, aged 15-78 years, all inpatients in general medical wards. 24 of the subjects studied had a spastic or irritable colon syndrome. To test lactose intolerance 50 g. of glucose-free lactose, diluted in 300 ml. of water, was administered to each fasting subject. Capillary blood samples were taken from the fingertip before ingestion of lactose and 15, 30, 60, 90, and 150 minutes after. Blood-glucose was estimated by the glucose-oxidase method. A rise in blood-glucose of 20 mg. per 100 ml. or more above fasting levels was considered as normal.
McMichael
et
1. 2.
Lancet, 1972, ii, 324. Spanidou, E. P., Petrakis, N. L. ibid. p. 872. 3. McMichael, H. B., Webb, J., Dawson, A. M. Br. med. J. 1966, ii, 1037.
4.
Neale, G. Proc. R. Soc. Med. 1968, 61, 1099.
Evangelismos Hospital, Athens 140, Greece.
N. ZOGRAFOS T. KANAGHINIS I. HATZIOANNOU C. GARDIKAS.
SIR,-We were very interested in the report by Spanidou and Petrakis1 pointing to a greater prevalence of lactose intolerance in 16 Greek students than in 13 Americans of northern European extraction, and to discrepancies between individuals with lactose intolerance and those with symptoms after milk-drinking. Several years ago McMichael et a1.2 and Neale3 suggested that the frequency of lactose intolerance may vary in different segments of the Greek population. We report here our findings in 82 healthy Greek children, aged 1-13 years. Lactose tolerance was tested in these healthy children in an attempt to evaluate its validity for the diagnosis of primary and secondary lactase deficiency in infants and children with chronic diarrhoea. The group consisted of 52 healthy boys and 30 girls with no clinical symptoms on ingestion of normal quantities of milk (200-500 ml. daily). They were given 2 g. per kg. bodyweight of glucose-free lactose, suspended as a 10% solution in tap-water. Venous blood samples, usually in duplicate, were drawn just before lactose ingestion and 30, 60, 90, and 120 minutes later. Blood-glucose was estimated by the glucose-oxidase method.4A child was regarded as lactosetolerant if the blood-glucose rose by more than 20 mg. per 100 ml. above fasting levels within 60 minutes of lactose
ingestion. A maximum increase of glucose by more than 20 mg. per 100 ml. was observed in 27 children (33%). The remaining 55 (67%) were by definition lactose-intolerant; in these children the rise of glucose levels varied widely. It is of particular interest that, of 55 lactose-intolerant children, in 22 (40%) glucose levels following ingestion of lactose were lower than fasting levels and all but 4 experienced symptoms (mainly abdominal distension and pain, and diarrhoea) after lactose ingestion. On the contrary, of the remaining 33 children in whom glucose levels rose by 2-20 mg. per 100 ml. only 4 had symptoms. None of the lactose-tolerant children had symptoms after ingesting lactose. These findings contrast with those of Spanidou and Petrakis; in our group, symptoms were experienced mainly by children in whom the lactose-tolerance test was grossly abnormal. This may be explained by the fact that these children can tolerate well the rather low total lactose content of the daily intake of milk but not the huge amount administered in the oral test. This confirms the clinical 1. 2.
Spanidou, E. P., Petrakis, N. L. Lancet, 1972, ii, 872. McMichael, H. B., Webb, J., Dawson, A. M. Br. med. J. 1966, ii,
3. 4.
Neale, G. Proc. R. Soc. Med. 1968, 61, 1099. Huggett, A: St. G., Nixon, D. A. Lancet, 1957, ii, 368.
1037.
368 that milk intolerance among Greek children is If there were any correlation between milk intolerance and the results of the lactose-tolerance test, many infants and younger children fed with sufficient quantities of milk might be expected to have severe disorders. Our findings, which are similar to those reported in a small number of Greek adults,indicate that the lactosetolerance test is abnormal in a high proportion of normal Greek children who have no symptoms after drinking normal quantities of milk. Whatever the explanation of this discrepancy may be, it is evident that the lactose-tolerance test is of little value in the diagnosis of primary or secondary lactose deficiency, at least in Greek infants and children.
impression
not common.
Department of Pædiatrics, Athens University, St. Sophie’s Children’s Hospital, Athens 608, Greece.
CHRISTOS KATTAMIS KALIOPI ANASTASSEAVLACHOU NICOLAS LOGOTHETIS VASILIKI SIRIOPOULOU NICOLAS MATSANIOTIS.
ROSETTE SEDIMENTATION FOR SEPARATION OF HUMAN T AND B CELLS SIR,-We were interested in the claim of Dr Wybran and his colleagues (Jan. 20, p. 126) that they have isolated normal T cells in chronic lymphatic leukaemia (C.L.L.). Although we have no information on C.L.L. we have been using a very similar method to fractionate the peripheral lymphocytes of normals and of patients with immunological defects. We have concluded that the lymphocytes which pass through the gradient together with sheep red blood-cells are a distinct subpopulation of T cells.I The lymphocytes which remain at the interface seem to consist of B cells together with a third population which may or may not be
wholly T cells. The principle of the method used by Dr Wybran and his associates and by ourselves is that lymphocytes which form rosettes (R.F.C.) will sediment, leaving non-R.F.c. at the interface. Different authors have found that between 4% and 81% of lymphocytes are R.F.c. In their recent work Wybran et al. claimed that approximately 67% of normal peripheral lymphocytes are R.F.c., but earlier reported a range of 4-40%. Unfortunately, they do not explain the rather dramatic increase and the increment may be at the cost of specificity. Our own experience and that of most others is more in line with the earlier report. Wybran et al. have found that after rosette sedimentation approximately 97% of the pellet cells were R.F.c., but so were 38% of the interface cells. Our own values are 27% and 0-6%, respectively, with the pellet cells accounting for between 10 and 30% of the peripheral lymphocytes layered into the gradient. We have therefore concluded that we have separated a subpopulation of T cells which form firm but transient rosettes. Wybran et al. do not indicate the proportion of the initial cells which reach the pellet and do not explain the apparently excessive number of R.F.c. which remain at the interface. Finally, Wybran et al. draw attention to the relatively high rate of spontaneous D.N.A. synthesis of the interface cells. Our own data (in preparation) are more notable for the low rate of synthesis of the pellet cells, and it is interesting that table 11 of Wybran et al. confirms our finding. We suggest that there may be a spectrum of rosette-forming capacity and that " tight R.F.C." are T cells with a low rate of D.N.A. synthesis. " Loose x..c." may be a more rapidly dividing T-cell subpopulation. Thus, D.N.A. synthesis and rosette-forming capacity could be 1.
Zilko, P. J., Dawkins, R. L. Unpublished.
inversely related, perhaps because rosette formation does not occur equally during the different phases of the cell cycle. At the very least, possibilities such as these suggest that it may be unwise to imply that the T cells which Wybran et al. claim to have separated are a homogeneous population. It may also be premature to state that normal T cells have been isolated in c.L.L. without indicating that different subpopulations should be considered. Department of Pathology, University of Western Australia, Perth, Western Australia 6000.
R. L. DAWKINS P. J. ZILKO.
RESUSCITATION AFTER ELECTRIC SHOCK
SIR9 The recommendations of Morley and CarterI referred to in your editorial of Feb. 3 (p. 244) are naturally of great interest to us, especially the reported high primary cardiac death-rate and the recommendation for two " thumps ". With this the Joint Manual almost entirely agrees, except that we are prepared to go up to ten. The suggestion that Holger Nielsen or Schafer, by virtue of movement of the limbs, has a beneficial cardiac as well as respiratory effect is very interesting. We think this may well be due to increased venous pressure acting as a stimulus in much the same manner that raising the legs may restart an arrested heart. The manual does in fact include Holger Nielsen (better than Schafer), although not for the reasons suggested by Morley and Carter, and our people are trained in it as an alternative to mouth-tomouth, which remains the most effective from a purely
respiratory standpoint. The other points raised in your last paragraph concerning training are important, and will certainly be considered when we come to produce the next edition. H. C.
STEWART,
Chief Medical Officer, St. John Ambulance Association.
H.Q. St. John Ambulance, 1 Grosvenor Crescent, London SW1.
ROBERT OLLERENSHAW, Surgeon-in-Chief, St. John Ambulance Brigade.
PREGNANCY IN WOMAN WITH MENINGOMYELOCELE SIR,-In response to the letter by Dr Fujimoto and his colleagues (Jan. 13, p. 104), I should like to report the
following
case.
A 35-year-old woman with a small lumbar meningomyelocele and mild paresis of the lower extremities was married at the age of 22. A year later she was delivered, at term, of a stillborn male infant with meningomyelocele, hydrocephalus, and a bilateral club-foot deformity. A therapeutic abortion was performed 10 years later when she became pregnant for the second time. At the age of 35 she became pregnant for the third time and was referred for genetic counselling. Her husband’s health, physical condition, and family history were unremarkable. A review of the patient’s family history showed that she had two normal siblings and two normal nephews; one sister who was otherwise normal died at 5 years during the 1939-45 war. In addition, she had had a sister who died at the age of 20 years of complications of a meningomyelocele. In 1966, when the couple were seen for genetic counselling, no similar case had been published and her genetic risk was not clear to me. They wanted a normal child very badly, but were " unwilling to continue the pregnancy if there was a significant chance that the baby might be born with a meningomyelocele. During a telephone call to Great Ormond Street, Dr Cedric Carter stated that the risk of fetal defect was about the same as for the case of normal parents who had had two affected infants to date. That risk he judged to be 1 in 7. This risk figure was unacceptable to the woman, so the "
1.
Morley, R., Carter, A. O. Archs envir. Hlth, 1972, 25, 276.