327 al.13 found that human newborns’ lymphocytes inhibited the division of their mothers’ lymphocytes (and not vice-versa, as you stated). This inhibition, which is mediated by T lymphocytes,14 could account for the difficulty in detecting maternal lymphocytes in cord blood by karyotyping, which depends on cell division. Subpopulations of T lymphocytes can be distinguished by their receptors for the Fc portion of IgG or IgM. Following appropriate stimulation both the IgG" and IgM 16 binding T cells can suppress the responses of other lymphocytes. The pro-
ing these changes fairly rapidly disappear so that the increases may be present for only a few days. This combination of laboratory findings is not restricted to alcoholism but taken with evidence from other sources may aid in its diagnosis.
et
Department of Psychiatry, ExeVale Hospital, Exeter EX2 5AF
portion of IgG-binding T cells (TG cells) is high in cord blood," and although Oldstone et al. 18 have attributed the suppressor activity of cord-blood T cells to this population their results do not substantiate more than a failure of TG cells to cooperate with adult lymphocytes. Multiple rather than single factors
HYPERVISCOSITY IN DISEASE
SiR,—You present’ a picture of viscosity-disease relationships which, though fair, has some deficiencies. "Blood viscosity" is a complex of viscosity factors in various subphases
which may suppress maternofetal immune interactions have been found, including fetal monocytes,9 soluble T-cell factors, 20 alpha-macroglobulin21 and, probably most important of all, maternal antibodies to tissue-type components. The live birth of infants with severe congenital immunodeficiencies argues against the need for fetal specific immunity mechanisms to protect the fetus in utero. The observations by Beer at al.,22 that maternal enhancing or blocking antibodies prevent damage to the fetus by maternal lymphocytes, provides a mechanism which may account for the intrauterine survival of infants with severe combined immunodeficiency.
London
A. R. HAYWARD P. M. LYDYARD
MACROCYTOSIS AND ALCOHOLISM
SiR,-I agree with Dr Wright and Dr Ree (Jan. 7, p. 49) that macrocytosis is a feature of alcoholism. In this laboratory the characteristic blood picture in an alcoholic is macrocytosis without anxmia. The mean corpuscular volume (’Coulter S’) is 97-105 fl, with occasional higher values. The haemoglobin level is normal. The blood-film shows uniform round macrocytosis with normal white cells and no neutrophil hypersegmentation. Serum-vitamin Bn and folate levels are normal. Round macrocytosis in the blood-film has revealed many unsuspected patients with an undiagnosed alcohol problem and alcohol abuse should thus be excluded in cases of macrocytosis without ana:mia before embarking on more expensive and tuhe-consuming serum-vitamin-B12 and folate assays. Department of Hæmatology, City Hospital, Aberdeen AB9 8AU
R. R. KHAUND
SiR,—The diagnosis of alcoholism continues to be difficult and is compounded by the frequent denial of illness by the affected person. However, biochemical and haematological analysis of a routine blood-sample can provide evidence of alcoholism. The combination to look for is macrocytosis without anaemia and a blood-urea below normal. This combination is found in many alcoholics when they are drinking, particularly beer drinkers. Raised blood-cholesterol and serumenzymes are also common. But once the alcoholic stops drink13. Lawler, S. D., Ukaejiofo, E. O., Reeves, B. R. Lancet, 1975, ii, 1185. 14. Olding, L. B., Oldstone, M. B. A. J. Immun. 1976, 116, 682. 15. Moretta, L., Webb, S. R., Grossi, C. E., Lydyard, P. M., Cooper, M. D. J.
exp. Med. 1977, 146, 184. 16. Hayward, A. R., and others. Unpublished. 17. Hayward, A. R., Lawton, A. R. J. Immun. 1977, 119, 1213. 18. Oldstone, M. B. A. Tishon, A., Moretta, L. Nature, 1977, 269, 333. 19. Wolf, R. L., Lomnitzer, R., Rabson, A. R. Clin. exp. Immun. 1977, 27, 464.
20. Olding, L. B., Murgita, R. A., Wigzell, H. J. Immun. 1977, 119, 1109. 21. Stimson, W. H. Clin. exp. Immun. 1976, 25, 199. 22. Beer, A. E., Billingham, R. E., Head, J. R., Parmely, M. J. in Development of Host Defenses (edited by M. D. Cooper and D. H. Dayton). New York, 1977.
of blood. In different diseases2 different factors are important. include not only viscosity of whole blood at different shear-rates but also viscosity of plasma, rigidity/deformability of red cells, aggregation of red cells, aggregation of platelets, and propensity to dynamic thrombus formation, not forgetting the oldest factor, haematocrit. In the microcirculation the main factor is not the viscosity of whole blood but the rigidity of red cells and presence or absence of platelet aggregates or microemboli. You say "we still await proof that changes in viscosity precede the clinical manifestations." In some instances we did find that blood-viscosity factors (not necessarily whole-blood viscosity) rose before the onset of occlusive arterial disease, kidney failure, or myocardial infarction, but I agree that additional proof is needed.3.4 You claim that peripheral resistance is influenced by the geometry and size of vessels in the microcirculation and by blood viscosity and that the hsematocrit is lower in arterioles and capillaries than in large vessels. Peripheral resistance is affected by rigidity of red cells, presence of microemboli and only lastly by the viscosity of whole blood. The hasmatocrit in small vessels may vary from zero to nearly 100%, depending on the degree of plasma skimming, the latter depending on the degree of aggregation of red cells.5 It is true that the relation of flow-rate to dnving-pressure in small vessels is linear and little affected by hmmatocrit, but it is greatly affected by the rigidity of red cells. You ask for more convincing evidence for the suggestion that "a reduction of heematocrit gives rise to an increase in cardiac output, owing to a reduction of blood viscosity." We did show that cardiac function, submaximal work, and physical fitness depends on blood-viscosity factors, even if haematocrit was nearly constant. 6-8 The influence of temperature on blood viscosity may not have been systematically investigated "as a means of improving tissue perfusion and reducing venous thrombosis", but we do know that fever leads to increased aggregation9 of red cells and increased viscosity of blood at low shear-rates, both predisposing to venous thrombosis. You are wrong to claim that "erythrocyte flexibility does not contribute to whole-blood viscosity at any shear-rate." It is a 5 very powerful factor at all shear-rates, especially high ones.2 The discussion of diabetes is tangled. Rheological factors are very different in diabetes of different degrees of severity." Some diabetics show increased red-cell aggregation or rigid-
They
Departments of Immunology, Institute of Child Health and Middlesex Hospital,
A. R. FOSTER
-
1. Lancet, 1977, ii, 961. 2. Dintenfass, L. Rheology of Blood in
Diagnostic and Preventive Medicine. London, 1976. 3. Dintenfass, L., Ibels, L. S. in Platelets: Recent Advances in Basic Research and Clinical Aspects (Excerpta med. int. Congr. Ser. 1974, no. 357); p. 315. 4. 5.
Dintenfass, L., Stewart, J. H. Thromb. Diath. hœmorrh. 1971, 26, 24. Dintenfass, L. Microrheology of Blood, Viscosity Factors in Blood Flow, Ischæmia and Thrombosis. London, 1971. 6. Lake, B., Dintenfass, L. Lancet, 1975, ii, 1092. 7. Dintenfass, L., Lake, B. Eur. surg. Res. 1976, 8, 174. 8. Dintenfass, L., Lake, B. Angiology, 1977, 28, 788. 9. Dintenfass, L., Forbes, C. D. Biorheology, 1973, 10, 383. 10. Dintenfass, L., Davis, E. Adv. Microcirculation, 1977, 7, 96.
328
ityll.12 (whole-blood viscosity can be lower than normal, probably a compensatory response’3 aimed at the integrity of the
ABSENCE OF VIRUS STRUCTURES IN CROHN’S DISEASE TISSUES STUDIED BY ELECTRON MICROSCOPY
microcirculation), but the role of fibrinogen is far from simple. Your editorial on hyperviscosity in disease covers the state of art nearer to
1975 than 1977.
Kanematsu Memorial
Institute,
Sydney Hospital, Sydney 2000, Australia
L. DINTENFASS
ROTAVIRUS INFECTION IN HIGH-INCIDENCE
LACTASE-DEFICIENCY POPULATION
SIR,-It has been postulated that lactase in the brush border of intestinal epithelial cells acts both as a receptor site and an uncoating enzyme for rotavirus.’ This hypothesis is based on the in-vitro ability of purified p-galactosidase to remove the outer capsid layer of the virus and could explain the tendency of rotavirus to infect infant animals and involve only gut epithelial cells. The incidence of persistent high intestinal lactase activity is low in certain ethnic groups. Of 20 Johannesburg Blacks of unspecified tribe, all were found to be deficient.2 Similarly, 13 Swazi, 4 Tswana, 50 Damara, and 5 Dama were all deficient,3 and of 58 Herero all but 2 were deficient.4 Only 1 of 40 Kalahari San ("bushmen") was lactose tolerant. The prevalence of rotavirus infection in these populations would thus provide an indication of the relative importance of lactase in the pathogenesis of rotavirus gastroenteritis. Our initial electronmicroscopic investigations of Black infantile gastroenteritis inpatients, all under the age of 2 years, showed a low incidence of 6-16%. However, by complement fixation tests, 69% of patients proved to be rotavirus positive7 a figure comparable with that in White communities in North America, the United Kingdom, and Australia.9 In addition, a seroepidemiological survey showed that Blacks had a more extensive exposure to rotavirus than Whites;’° rotavirus antibodies, measured by immunofluorescence, were present in 87 of 94 (93%) adult Blacks compared with 72 of 94 (77%) adult Whites (p
ing these changes fairly rapidly disappear so that the increases may be present for only a few days. This combination of laboratory findings is not restricted to alcoholism but taken with evidence from other sources may aid in its diagnosis.
et
Department of Psychiatry, ExeVale Hospital, Exeter EX2 5AF
portion of IgG-binding T cells (TG cells) is high in cord blood," and although Oldstone et al. 18 have attributed the suppressor activity of cord-blood T cells to this population their results do not substantiate more than a failure of TG cells to cooperate with adult lymphocytes. Multiple rather than single factors
HYPERVISCOSITY IN DISEASE
SiR,—You present’ a picture of viscosity-disease relationships which, though fair, has some deficiencies. "Blood viscosity" is a complex of viscosity factors in various subphases
which may suppress maternofetal immune interactions have been found, including fetal monocytes,9 soluble T-cell factors, 20 alpha-macroglobulin21 and, probably most important of all, maternal antibodies to tissue-type components. The live birth of infants with severe congenital immunodeficiencies argues against the need for fetal specific immunity mechanisms to protect the fetus in utero. The observations by Beer at al.,22 that maternal enhancing or blocking antibodies prevent damage to the fetus by maternal lymphocytes, provides a mechanism which may account for the intrauterine survival of infants with severe combined immunodeficiency.
London
A. R. HAYWARD P. M. LYDYARD
MACROCYTOSIS AND ALCOHOLISM
SiR,-I agree with Dr Wright and Dr Ree (Jan. 7, p. 49) that macrocytosis is a feature of alcoholism. In this laboratory the characteristic blood picture in an alcoholic is macrocytosis without anxmia. The mean corpuscular volume (’Coulter S’) is 97-105 fl, with occasional higher values. The haemoglobin level is normal. The blood-film shows uniform round macrocytosis with normal white cells and no neutrophil hypersegmentation. Serum-vitamin Bn and folate levels are normal. Round macrocytosis in the blood-film has revealed many unsuspected patients with an undiagnosed alcohol problem and alcohol abuse should thus be excluded in cases of macrocytosis without ana:mia before embarking on more expensive and tuhe-consuming serum-vitamin-B12 and folate assays. Department of Hæmatology, City Hospital, Aberdeen AB9 8AU
R. R. KHAUND
SiR,—The diagnosis of alcoholism continues to be difficult and is compounded by the frequent denial of illness by the affected person. However, biochemical and haematological analysis of a routine blood-sample can provide evidence of alcoholism. The combination to look for is macrocytosis without anaemia and a blood-urea below normal. This combination is found in many alcoholics when they are drinking, particularly beer drinkers. Raised blood-cholesterol and serumenzymes are also common. But once the alcoholic stops drink13. Lawler, S. D., Ukaejiofo, E. O., Reeves, B. R. Lancet, 1975, ii, 1185. 14. Olding, L. B., Oldstone, M. B. A. J. Immun. 1976, 116, 682. 15. Moretta, L., Webb, S. R., Grossi, C. E., Lydyard, P. M., Cooper, M. D. J.
exp. Med. 1977, 146, 184. 16. Hayward, A. R., and others. Unpublished. 17. Hayward, A. R., Lawton, A. R. J. Immun. 1977, 119, 1213. 18. Oldstone, M. B. A. Tishon, A., Moretta, L. Nature, 1977, 269, 333. 19. Wolf, R. L., Lomnitzer, R., Rabson, A. R. Clin. exp. Immun. 1977, 27, 464.
20. Olding, L. B., Murgita, R. A., Wigzell, H. J. Immun. 1977, 119, 1109. 21. Stimson, W. H. Clin. exp. Immun. 1976, 25, 199. 22. Beer, A. E., Billingham, R. E., Head, J. R., Parmely, M. J. in Development of Host Defenses (edited by M. D. Cooper and D. H. Dayton). New York, 1977.
of blood. In different diseases2 different factors are important. include not only viscosity of whole blood at different shear-rates but also viscosity of plasma, rigidity/deformability of red cells, aggregation of red cells, aggregation of platelets, and propensity to dynamic thrombus formation, not forgetting the oldest factor, haematocrit. In the microcirculation the main factor is not the viscosity of whole blood but the rigidity of red cells and presence or absence of platelet aggregates or microemboli. You say "we still await proof that changes in viscosity precede the clinical manifestations." In some instances we did find that blood-viscosity factors (not necessarily whole-blood viscosity) rose before the onset of occlusive arterial disease, kidney failure, or myocardial infarction, but I agree that additional proof is needed.3.4 You claim that peripheral resistance is influenced by the geometry and size of vessels in the microcirculation and by blood viscosity and that the hsematocrit is lower in arterioles and capillaries than in large vessels. Peripheral resistance is affected by rigidity of red cells, presence of microemboli and only lastly by the viscosity of whole blood. The hasmatocrit in small vessels may vary from zero to nearly 100%, depending on the degree of plasma skimming, the latter depending on the degree of aggregation of red cells.5 It is true that the relation of flow-rate to dnving-pressure in small vessels is linear and little affected by hmmatocrit, but it is greatly affected by the rigidity of red cells. You ask for more convincing evidence for the suggestion that "a reduction of heematocrit gives rise to an increase in cardiac output, owing to a reduction of blood viscosity." We did show that cardiac function, submaximal work, and physical fitness depends on blood-viscosity factors, even if haematocrit was nearly constant. 6-8 The influence of temperature on blood viscosity may not have been systematically investigated "as a means of improving tissue perfusion and reducing venous thrombosis", but we do know that fever leads to increased aggregation9 of red cells and increased viscosity of blood at low shear-rates, both predisposing to venous thrombosis. You are wrong to claim that "erythrocyte flexibility does not contribute to whole-blood viscosity at any shear-rate." It is a 5 very powerful factor at all shear-rates, especially high ones.2 The discussion of diabetes is tangled. Rheological factors are very different in diabetes of different degrees of severity." Some diabetics show increased red-cell aggregation or rigid-
They
Departments of Immunology, Institute of Child Health and Middlesex Hospital,
A. R. FOSTER
-
1. Lancet, 1977, ii, 961. 2. Dintenfass, L. Rheology of Blood in
Diagnostic and Preventive Medicine. London, 1976. 3. Dintenfass, L., Ibels, L. S. in Platelets: Recent Advances in Basic Research and Clinical Aspects (Excerpta med. int. Congr. Ser. 1974, no. 357); p. 315. 4. 5.
Dintenfass, L., Stewart, J. H. Thromb. Diath. hœmorrh. 1971, 26, 24. Dintenfass, L. Microrheology of Blood, Viscosity Factors in Blood Flow, Ischæmia and Thrombosis. London, 1971. 6. Lake, B., Dintenfass, L. Lancet, 1975, ii, 1092. 7. Dintenfass, L., Lake, B. Eur. surg. Res. 1976, 8, 174. 8. Dintenfass, L., Lake, B. Angiology, 1977, 28, 788. 9. Dintenfass, L., Forbes, C. D. Biorheology, 1973, 10, 383. 10. Dintenfass, L., Davis, E. Adv. Microcirculation, 1977, 7, 96.
328
ityll.12 (whole-blood viscosity can be lower than normal, probably a compensatory response’3 aimed at the integrity of the
ABSENCE OF VIRUS STRUCTURES IN CROHN’S DISEASE TISSUES STUDIED BY ELECTRON MICROSCOPY
microcirculation), but the role of fibrinogen is far from simple. Your editorial on hyperviscosity in disease covers the state of art nearer to
1975 than 1977.
Kanematsu Memorial
Institute,
Sydney Hospital, Sydney 2000, Australia
L. DINTENFASS
ROTAVIRUS INFECTION IN HIGH-INCIDENCE
LACTASE-DEFICIENCY POPULATION
SIR,-It has been postulated that lactase in the brush border of intestinal epithelial cells acts both as a receptor site and an uncoating enzyme for rotavirus.’ This hypothesis is based on the in-vitro ability of purified p-galactosidase to remove the outer capsid layer of the virus and could explain the tendency of rotavirus to infect infant animals and involve only gut epithelial cells. The incidence of persistent high intestinal lactase activity is low in certain ethnic groups. Of 20 Johannesburg Blacks of unspecified tribe, all were found to be deficient.2 Similarly, 13 Swazi, 4 Tswana, 50 Damara, and 5 Dama were all deficient,3 and of 58 Herero all but 2 were deficient.4 Only 1 of 40 Kalahari San ("bushmen") was lactose tolerant. The prevalence of rotavirus infection in these populations would thus provide an indication of the relative importance of lactase in the pathogenesis of rotavirus gastroenteritis. Our initial electronmicroscopic investigations of Black infantile gastroenteritis inpatients, all under the age of 2 years, showed a low incidence of 6-16%. However, by complement fixation tests, 69% of patients proved to be rotavirus positive7 a figure comparable with that in White communities in North America, the United Kingdom, and Australia.9 In addition, a seroepidemiological survey showed that Blacks had a more extensive exposure to rotavirus than Whites;’° rotavirus antibodies, measured by immunofluorescence, were present in 87 of 94 (93%) adult Blacks compared with 72 of 94 (77%) adult Whites (p
