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IMMUNOGLOBULINS IN FIRST-DEGREE RELATIVES OF PATIENTS WITH HYPOGAMMAGLOBULINÆMIA
1001
IMMUNOGLOBULINS IN FIRST-DEGREE RELATIVES OF PATIENTS WITH HYPOGAMMAGLOBULINÆMIA Transient Hypogammaglobulinæmia: A Possible Manifestation of Heterozygocity
J. F. SOOTHILL M.A., M.B. Cantab., M.R.C.P., M.C.Path. HEAD, DEPARTMENT OF IMMUNOLOGY, INSTITUTE OF CHILD HEALTH, LONDON W.C.1
Only two out of eleven first-degree relatives of patients with hypogammaglobulinæmia, whose IgG, IgM, and IgA were followed from birth, were normal. They were both girls. Four developed typical sex-linked hypogammaglobulinæmia. The IgM values were the first to reveal the abnormality. Five had a less severe, and perhaps transient, IgG deficiency. IgA was also rather low, but IgM was normal. They were relatives of patients with hypogammaglobulinæmia other than the sex-linked form, including the combined immunity-deficiency syndrome. Summary
and with the mean control data, but the four boys with persistent IgG deficiency all had much lower IgM. In two of them there was an initial unexplained fall; then the IgM rose, as is normal after birth, but this rise started from an abnormally low level, was abnormally small, and occurred abnormally late. Thus IgM values separate the population, divisible into three groups by IgG values, into two groups, which are distinct and clearly separated. The IgA data are less clear-cut, but they are essentially similar to the IgG data-the two unaffected sisters follow the normal curve, the four fully affected boys give the lowest values, and the other five are intermediate. The accompanying table summarises data on the patients whose first-degree relatives these are, including immunoglobulin concentrations and lymphocyte-counts at diagnosis. All the infants who were shown to have gross deficiency of IgG and IgM were brothers of boys with
Introduction
TRANSIENT hypogammaglobulinaemia was well described by Gitlin and Janeway (1956), but it has remained an isolated phenomenon unrelated to any of the various permanent and familial immunity-deficiency diseases. For ten years, every opportunity has been taken to make serial estimations of immunoglobulins in the serum of newborn first-degree relatives of patients with hypogammaglobulinxmia satisfying the diagnostic criteria of the M.R.C. Working Party for Hypogammaglobulinmmia (Squire 1960), which included a wide variety of primary hypogammaglobulinsemia, such as the sex-linked form, the combined immunity-deficiency syndrome, and acquired forms in adults and children. Eleven such infants have been studied. Gel-diffusion precipitin techniques were used-either a double-diffusion method (Gell 1957) or a single-diffusion method (modification of the method of Fahey and McKelvey 1965). Soothill and Rowe (1967) have shown that these methods correlate well. Results for IgG are expressed as mg. per 100 ml. in terms of a purified IgG standard, and results for IgM and IgA are expressed as a percentage of a reference serum from a healthy adult male (R.N.S.). Results
The results for the eleven patients are shown in fig. 1, with approximate mean values for healthy populations obtained from other reported series and from our own data. In only two did the IgG levels conform to the normal curve, and both patients were girls. The rest fell into two groups-in four boys the IgG fell to very low values as the maternal IgG decayed, and y-globulin treatment was started (interrupted lines in the figure). The other five were clearly abnormal after 30 weeks for the rest of the period of study, though their IgG values were higher than those of the patients with gross hypogammaglobulinoemia. Two had little evidence of abnormal tendency to infection; but the other three did have frequent infections; and one of these (case 7), who was worryingly ill for a while, and was given y-globulin, has subsequently attained a normal level of IgG at 3 years (IgG 1360 mg. per 100 ml., IgA 10% R.N.S., IgM 272%
R.N.S.). The IgM levels for this intermediate group coincided very precisely with those of the two girls with normal IgG,
Fig. 1-Serial estimations of IgG, IgM, and IgA in the serum of eleven newborn first-degree relatives of patients with hypogammaglobulinaemia.
IgG values are shown by interrupted lines when the patients were receiving y-globulin injections. Closed symbols are used for the four girls and open symbols for the seven boys. The heavy line gives approximate mean values in healthy populations, obtained from
published data.
1002 DATA ON FIRST-DEGREE RELATIVES OF ELEVEN PATIENTS WITH HYPOGAMMAGLOBULINaeMIA
typical antibody-deficiency syndrome associated with hypogammaglobulinaemia. The impression of sex-linked inheritance is further supported in two by the affected maternal first cousin and maternal half-brother. The affected relatives of the two girls who were apparently normal were a sister, with no other family history of immunity deficiency, and two affected brothers, one of whom (case 8) was her twin, and was followed in parallel. The intermediate group were relatives of patients with less common forms of immunity deficiency. Discussion
This follow-up study of serum-immunoglobulin concentrations from birth on first-degree relatives of patients with hypogammaglobulinasmia, not selected by any preconceived hypothesis of relationship but purely by the desire of physicians or parents that it should be done, yields the remarkable result that only two of the eleven infants studied can be regarded as normal. The detection of typical sex-linked hypogammaglobulinaemia was expected, and it is interesting to note that in these individuals the abnormality can first be detected by the IgM values. It was detectable in all at birth, and the subsequent normal rise occurred; but it started too low, occurred too late, and did not rise high enough. It is probable that some newborn children, who will subsequently have IgG deficiency, will have very low, normal, or high IgM levels, as occurs later in life (Soothill 1962) (the brother of patient 9 had an abnormally high value); but, when abnormal, the IgM value is of diagnostic value in these cases. It is highly probable that the child’s own IgG production is equivalently reduced, but this is masked during the first weeks of life by the maternal
gammaglobulinxmia, whose IgG production deficiency, though of long standing, was rather varied (fig. 2). Of the three boys, one had an affected sister, another had both an affected brother and an aunt with thymoma and myasthenia gravis, and the third had two brothers with fatal combined immunity deficiency (for nomenclature, see Soothill 1968). It is in newborn relatives of such unusual patients that transient hypogammaglobulinsemia must be sought. Clearly, IgG is an insensitive diagnostic test, because of the maternal IgG; IgM values were normal in this series; possibly the rather more scattered IgA values may provide the best means of detection, though more data are required to confirm this. Treatment for those with frequent infections is presumably antibiotics or y-globulin injections. The possibility that y-globulin might inhibit the child’s own production must be considered, since deficient antibody production is known to result from passive transfer of antibody in certain experimental situations (Brody et al. 1967), but there is no evidence that this happened in
IgG. The intermediate group are the most interesting. Only gave much grounds for clinical concern because of infections; his serum-IgG has subsequently risen to normal, and he is well. Gitlin and Janeway (1956) clearly described transient hypogammaglobulinsemia, but did not relate it to the more severe and persistent forms. Since such patients may attain normal immunological competence, early diagnosis and effective treatment to avoid irreversible damage are highly desirable. The relatives of cur five patients were all rather unusual, as is shown in the table. Two were the daughters of a woman with hypoone
Fig. 2-Serial estimations of IgG in the mother of patients 3 and 4 during six years of y-globulin treatment, and covering the period of two pregnancies. The cord-blood value in the first child is indicated by X.
1003
patient no. 7, y-globulin.
the
only
one
of this group treated with
The association of transient hypogammaglobulina:mia with normal levels of IgM is perhaps related to the observation that patients with long-standing IgG deficiency are more liable to some remission if the IgM is normal or high (Soothill 1962). Such varied patterns already exist in different members of the same family (including some of those reported here). If transient hypogammaglobulinaemia is indeed genetically related to some other forms of hypogamrnaglobulinxmia, it may be a manifestation of a single gene effect in the heterozygous state of an autosomal recessive inheritance phenomenon. But the familial pattern is so complex that this hypothesis would require considerable further support. Thanks are due to the physicians who collected the specimens and encouraged the study, to Dr. D. S. Rowe for some of the deter’minations, and to the M.R.C. Working Party on Hypogammaglobulinxmia for permission to publish the data on the affected relatives.
Requests for reprints should be addressed to J. F. S., Department of Immunology, Institute of Child Health, 30 Guilford Street, London W.C.1. REFERENCES
Brody, N. I., Walker, J. G., Siskind, G. W. (1967) J. exp. Med. 126, 81. Fahey, J. L., McKelvey, E. M. (1965) J. Immun. 94, 84. Gell, P. G. H. (1957) J. clin. Path. 10, 67. Gitlin, D., Janeway, C. A. (1956) Prog. Hemat. 1, 318. Soothill, J. F. (1962) Clin. Sci. 23, 27. (1968) in Clinical Aspects of Immunology (edited by P. G. H. Gell and R. R. A. Coombs). Oxford. Rowe, D. S. (1967) International Symposium on Immunological Methods of Biological Standardisation, Royaumont, 1965. Symposium Series on Immunobiological Standard, vol. IV, p. 37. Basle. Squire, J. R. (1960) Acta hœmat. 24, 99. —
—
that, although plasma-testosterone levels of Kenyan and British men are the same (Wang et al. 1966), African men excrete less urinary ll-deoxy-17-oxosteroids (11-D.17-o.s.) and more urinary cestrogens than British men (Clifford and Bulbrook 1966). It does not follow that, because Kenyan men excrete less ll-D.-17-o.s. than comparable British men, plasma-levels of 17-oxosteroids (17-o.s.) are also lower. For example, the major plasma-17-o.s., dehydroepiandrosterone sulphate (D.s.), and androsterone sulphate (A.s.), might be cleared more slowly in African men. The purpose of the present
investigation was to determine whether the levels of plasma D.s. and A.S. in Kenyans are different from those in British men, and to see whether the levels of these steroids might be related in any way to the aetiology of
nasopharyngeal
cancer.
Methods Heparinised blood was taken from Kenyans* shortly after admission to hospital; the plasma was then separated and stored at -20°C. The frozen plasma, packed in solid carbon dioxide, was transported by air to London. All specimens were still frozen on arrival. There were 26 Kenyans (agerange 19-75 years) undergoing treatment for a variety of minor illnesses not connected with their endocrine system, and 14 Kenyans (age-range 18-65 years) with cancer of the nasopharynx. The British men who acted as controls for this study were as described by Wang, Bulbrook, Thomas, and Friedman (1968). Plasma D.s. and A.S. were estimated by the method of Wang et al. (1968), using gas-liquid chromatography and 5ae-dihyrotestosterone sulphate as an internal standard to correct for any losses in the method. The specificity, accuracy, and precision of this method have already been described (Wang et al. 1968). Results
PLASMA-LEVELS OF THE SULPHATE ESTERS OF DEHYDROEPIANDROSTERONE AND ANDROSTERONE IN KENYAN MEN AND THEIR RELATION TO CANCER OF THE NASOPHARYNX D. Y. WANG R. D. BULBROOK M.Sc., Ph.D. Load. M.Sc., Ph.D. Lond. PETER CLIFFORD M.Ch. N.U.I., D.L.O. From the Division of Chemistry and Biochemistry, Imperial Cancer Research Fund, Lincoln’s Inn Fields, London W.C.2, and the Department of Head and Neck Surgery, Kenyatta National Hospital, Nairobi, Kenya
Plasma
dehydroepiandrosterone-sulphate Summary and androsterone-sulphate levels were determined in 40 Kenyan men. These levels were not correlated with age and were lower than those found in British men. Kenyans with nasopharyngeal cancers had significantly lower levels of plasma-dehydroepiandrosterone-sulphate than control Kenyans, although androsterone-sulphate levels were similar. Introduction THE increased frequency of nasopharyngeal cancer in Kenya compared with Great Britain (Clifford 1965 and 1967), and the fact that the disease is more common in
than in women, have led to various studies to determine whether endocrine abnormalities in Kenyan men are a predisposing factor in the disease (Clifford and Bulbrook 1966, Wang, Bulbrook, and Clifford 1966). Studies of the endocrine status of Kenyans with nasopharyngeal cancer and of normal controls have established men
Plasma D.S. and A.S. in Normal to
Kenyans, and Relation
Age
The levels of D.S. and A.s. in the plasma of normal Kenyans and Kenyans with nasopharyngeal cancer are shown in figs. 1 and 2, respectively. There was a large variation between the values. Similar variabilities have been observed for plasma D.s. and A.s. in Europeans (Vihko 1966, Conrad et al. 1965, Wang et al. 1968) and for urinary ll-D.-17-o.s. in Africans (Clifford and Bulbrook 1966). There was no correlation between the values of either D.s. or A.s. and age in normal Kenyan men. However, linear regression lines have been calculated since they best represent the data. Plasma-levels of D.S. and A.S. in Kenyans with Nasopharyngeal Cancer The levels of plasma D.s. found in Kenyans with nasopharyngeal cancers (fig. 1) were generally somewhat lower than in the control group. The mean levels of these two groups, 50-4 and 85-4 g. per 100 ml. plasma respectively, were just different statistically (P 0-02). The mean levels of plasma A.S. were very similar (27-3 and 25-8 g. per 100 ml. for the control and cancer =
respectively). Plasma-levels of D.S. and A.S. in Kenyan and British Men The linear regression lines for plasma D.s. and A.s. with age for British men have been included in figs. 1 and 2. These regression lines were calculated from results obtained from assays of the plasma-steroids of 41 normal British men, described in detail elsewhere (Wang et al. 1968). groups,
*
This refers to Central and ethnic groups.
Nyanza Bantu, Nilotic and Nilo-Hamitic
IMMUNOGLOBULINS IN FIRST-DEGREE RELATIVES OF PATIENTS WITH HYPOGAMMAGLOBULINÆMIA Transient Hypogammaglobulinæmia: A Possible Manifestation of Heterozygocity
J. F. SOOTHILL M.A., M.B. Cantab., M.R.C.P., M.C.Path. HEAD, DEPARTMENT OF IMMUNOLOGY, INSTITUTE OF CHILD HEALTH, LONDON W.C.1
Only two out of eleven first-degree relatives of patients with hypogammaglobulinæmia, whose IgG, IgM, and IgA were followed from birth, were normal. They were both girls. Four developed typical sex-linked hypogammaglobulinæmia. The IgM values were the first to reveal the abnormality. Five had a less severe, and perhaps transient, IgG deficiency. IgA was also rather low, but IgM was normal. They were relatives of patients with hypogammaglobulinæmia other than the sex-linked form, including the combined immunity-deficiency syndrome. Summary
and with the mean control data, but the four boys with persistent IgG deficiency all had much lower IgM. In two of them there was an initial unexplained fall; then the IgM rose, as is normal after birth, but this rise started from an abnormally low level, was abnormally small, and occurred abnormally late. Thus IgM values separate the population, divisible into three groups by IgG values, into two groups, which are distinct and clearly separated. The IgA data are less clear-cut, but they are essentially similar to the IgG data-the two unaffected sisters follow the normal curve, the four fully affected boys give the lowest values, and the other five are intermediate. The accompanying table summarises data on the patients whose first-degree relatives these are, including immunoglobulin concentrations and lymphocyte-counts at diagnosis. All the infants who were shown to have gross deficiency of IgG and IgM were brothers of boys with
Introduction
TRANSIENT hypogammaglobulinaemia was well described by Gitlin and Janeway (1956), but it has remained an isolated phenomenon unrelated to any of the various permanent and familial immunity-deficiency diseases. For ten years, every opportunity has been taken to make serial estimations of immunoglobulins in the serum of newborn first-degree relatives of patients with hypogammaglobulinxmia satisfying the diagnostic criteria of the M.R.C. Working Party for Hypogammaglobulinmmia (Squire 1960), which included a wide variety of primary hypogammaglobulinsemia, such as the sex-linked form, the combined immunity-deficiency syndrome, and acquired forms in adults and children. Eleven such infants have been studied. Gel-diffusion precipitin techniques were used-either a double-diffusion method (Gell 1957) or a single-diffusion method (modification of the method of Fahey and McKelvey 1965). Soothill and Rowe (1967) have shown that these methods correlate well. Results for IgG are expressed as mg. per 100 ml. in terms of a purified IgG standard, and results for IgM and IgA are expressed as a percentage of a reference serum from a healthy adult male (R.N.S.). Results
The results for the eleven patients are shown in fig. 1, with approximate mean values for healthy populations obtained from other reported series and from our own data. In only two did the IgG levels conform to the normal curve, and both patients were girls. The rest fell into two groups-in four boys the IgG fell to very low values as the maternal IgG decayed, and y-globulin treatment was started (interrupted lines in the figure). The other five were clearly abnormal after 30 weeks for the rest of the period of study, though their IgG values were higher than those of the patients with gross hypogammaglobulinoemia. Two had little evidence of abnormal tendency to infection; but the other three did have frequent infections; and one of these (case 7), who was worryingly ill for a while, and was given y-globulin, has subsequently attained a normal level of IgG at 3 years (IgG 1360 mg. per 100 ml., IgA 10% R.N.S., IgM 272%
R.N.S.). The IgM levels for this intermediate group coincided very precisely with those of the two girls with normal IgG,
Fig. 1-Serial estimations of IgG, IgM, and IgA in the serum of eleven newborn first-degree relatives of patients with hypogammaglobulinaemia.
IgG values are shown by interrupted lines when the patients were receiving y-globulin injections. Closed symbols are used for the four girls and open symbols for the seven boys. The heavy line gives approximate mean values in healthy populations, obtained from
published data.
1002 DATA ON FIRST-DEGREE RELATIVES OF ELEVEN PATIENTS WITH HYPOGAMMAGLOBULINaeMIA
typical antibody-deficiency syndrome associated with hypogammaglobulinaemia. The impression of sex-linked inheritance is further supported in two by the affected maternal first cousin and maternal half-brother. The affected relatives of the two girls who were apparently normal were a sister, with no other family history of immunity deficiency, and two affected brothers, one of whom (case 8) was her twin, and was followed in parallel. The intermediate group were relatives of patients with less common forms of immunity deficiency. Discussion
This follow-up study of serum-immunoglobulin concentrations from birth on first-degree relatives of patients with hypogammaglobulinasmia, not selected by any preconceived hypothesis of relationship but purely by the desire of physicians or parents that it should be done, yields the remarkable result that only two of the eleven infants studied can be regarded as normal. The detection of typical sex-linked hypogammaglobulinaemia was expected, and it is interesting to note that in these individuals the abnormality can first be detected by the IgM values. It was detectable in all at birth, and the subsequent normal rise occurred; but it started too low, occurred too late, and did not rise high enough. It is probable that some newborn children, who will subsequently have IgG deficiency, will have very low, normal, or high IgM levels, as occurs later in life (Soothill 1962) (the brother of patient 9 had an abnormally high value); but, when abnormal, the IgM value is of diagnostic value in these cases. It is highly probable that the child’s own IgG production is equivalently reduced, but this is masked during the first weeks of life by the maternal
gammaglobulinxmia, whose IgG production deficiency, though of long standing, was rather varied (fig. 2). Of the three boys, one had an affected sister, another had both an affected brother and an aunt with thymoma and myasthenia gravis, and the third had two brothers with fatal combined immunity deficiency (for nomenclature, see Soothill 1968). It is in newborn relatives of such unusual patients that transient hypogammaglobulinsemia must be sought. Clearly, IgG is an insensitive diagnostic test, because of the maternal IgG; IgM values were normal in this series; possibly the rather more scattered IgA values may provide the best means of detection, though more data are required to confirm this. Treatment for those with frequent infections is presumably antibiotics or y-globulin injections. The possibility that y-globulin might inhibit the child’s own production must be considered, since deficient antibody production is known to result from passive transfer of antibody in certain experimental situations (Brody et al. 1967), but there is no evidence that this happened in
IgG. The intermediate group are the most interesting. Only gave much grounds for clinical concern because of infections; his serum-IgG has subsequently risen to normal, and he is well. Gitlin and Janeway (1956) clearly described transient hypogammaglobulinsemia, but did not relate it to the more severe and persistent forms. Since such patients may attain normal immunological competence, early diagnosis and effective treatment to avoid irreversible damage are highly desirable. The relatives of cur five patients were all rather unusual, as is shown in the table. Two were the daughters of a woman with hypoone
Fig. 2-Serial estimations of IgG in the mother of patients 3 and 4 during six years of y-globulin treatment, and covering the period of two pregnancies. The cord-blood value in the first child is indicated by X.
1003
patient no. 7, y-globulin.
the
only
one
of this group treated with
The association of transient hypogammaglobulina:mia with normal levels of IgM is perhaps related to the observation that patients with long-standing IgG deficiency are more liable to some remission if the IgM is normal or high (Soothill 1962). Such varied patterns already exist in different members of the same family (including some of those reported here). If transient hypogammaglobulinaemia is indeed genetically related to some other forms of hypogamrnaglobulinxmia, it may be a manifestation of a single gene effect in the heterozygous state of an autosomal recessive inheritance phenomenon. But the familial pattern is so complex that this hypothesis would require considerable further support. Thanks are due to the physicians who collected the specimens and encouraged the study, to Dr. D. S. Rowe for some of the deter’minations, and to the M.R.C. Working Party on Hypogammaglobulinxmia for permission to publish the data on the affected relatives.
Requests for reprints should be addressed to J. F. S., Department of Immunology, Institute of Child Health, 30 Guilford Street, London W.C.1. REFERENCES
Brody, N. I., Walker, J. G., Siskind, G. W. (1967) J. exp. Med. 126, 81. Fahey, J. L., McKelvey, E. M. (1965) J. Immun. 94, 84. Gell, P. G. H. (1957) J. clin. Path. 10, 67. Gitlin, D., Janeway, C. A. (1956) Prog. Hemat. 1, 318. Soothill, J. F. (1962) Clin. Sci. 23, 27. (1968) in Clinical Aspects of Immunology (edited by P. G. H. Gell and R. R. A. Coombs). Oxford. Rowe, D. S. (1967) International Symposium on Immunological Methods of Biological Standardisation, Royaumont, 1965. Symposium Series on Immunobiological Standard, vol. IV, p. 37. Basle. Squire, J. R. (1960) Acta hœmat. 24, 99. —
—
that, although plasma-testosterone levels of Kenyan and British men are the same (Wang et al. 1966), African men excrete less urinary ll-deoxy-17-oxosteroids (11-D.17-o.s.) and more urinary cestrogens than British men (Clifford and Bulbrook 1966). It does not follow that, because Kenyan men excrete less ll-D.-17-o.s. than comparable British men, plasma-levels of 17-oxosteroids (17-o.s.) are also lower. For example, the major plasma-17-o.s., dehydroepiandrosterone sulphate (D.s.), and androsterone sulphate (A.s.), might be cleared more slowly in African men. The purpose of the present
investigation was to determine whether the levels of plasma D.s. and A.S. in Kenyans are different from those in British men, and to see whether the levels of these steroids might be related in any way to the aetiology of
nasopharyngeal
cancer.
Methods Heparinised blood was taken from Kenyans* shortly after admission to hospital; the plasma was then separated and stored at -20°C. The frozen plasma, packed in solid carbon dioxide, was transported by air to London. All specimens were still frozen on arrival. There were 26 Kenyans (agerange 19-75 years) undergoing treatment for a variety of minor illnesses not connected with their endocrine system, and 14 Kenyans (age-range 18-65 years) with cancer of the nasopharynx. The British men who acted as controls for this study were as described by Wang, Bulbrook, Thomas, and Friedman (1968). Plasma D.s. and A.S. were estimated by the method of Wang et al. (1968), using gas-liquid chromatography and 5ae-dihyrotestosterone sulphate as an internal standard to correct for any losses in the method. The specificity, accuracy, and precision of this method have already been described (Wang et al. 1968). Results
PLASMA-LEVELS OF THE SULPHATE ESTERS OF DEHYDROEPIANDROSTERONE AND ANDROSTERONE IN KENYAN MEN AND THEIR RELATION TO CANCER OF THE NASOPHARYNX D. Y. WANG R. D. BULBROOK M.Sc., Ph.D. Load. M.Sc., Ph.D. Lond. PETER CLIFFORD M.Ch. N.U.I., D.L.O. From the Division of Chemistry and Biochemistry, Imperial Cancer Research Fund, Lincoln’s Inn Fields, London W.C.2, and the Department of Head and Neck Surgery, Kenyatta National Hospital, Nairobi, Kenya
Plasma
dehydroepiandrosterone-sulphate Summary and androsterone-sulphate levels were determined in 40 Kenyan men. These levels were not correlated with age and were lower than those found in British men. Kenyans with nasopharyngeal cancers had significantly lower levels of plasma-dehydroepiandrosterone-sulphate than control Kenyans, although androsterone-sulphate levels were similar. Introduction THE increased frequency of nasopharyngeal cancer in Kenya compared with Great Britain (Clifford 1965 and 1967), and the fact that the disease is more common in
than in women, have led to various studies to determine whether endocrine abnormalities in Kenyan men are a predisposing factor in the disease (Clifford and Bulbrook 1966, Wang, Bulbrook, and Clifford 1966). Studies of the endocrine status of Kenyans with nasopharyngeal cancer and of normal controls have established men
Plasma D.S. and A.S. in Normal to
Kenyans, and Relation
Age
The levels of D.S. and A.s. in the plasma of normal Kenyans and Kenyans with nasopharyngeal cancer are shown in figs. 1 and 2, respectively. There was a large variation between the values. Similar variabilities have been observed for plasma D.s. and A.s. in Europeans (Vihko 1966, Conrad et al. 1965, Wang et al. 1968) and for urinary ll-D.-17-o.s. in Africans (Clifford and Bulbrook 1966). There was no correlation between the values of either D.s. or A.s. and age in normal Kenyan men. However, linear regression lines have been calculated since they best represent the data. Plasma-levels of D.S. and A.S. in Kenyans with Nasopharyngeal Cancer The levels of plasma D.s. found in Kenyans with nasopharyngeal cancers (fig. 1) were generally somewhat lower than in the control group. The mean levels of these two groups, 50-4 and 85-4 g. per 100 ml. plasma respectively, were just different statistically (P 0-02). The mean levels of plasma A.S. were very similar (27-3 and 25-8 g. per 100 ml. for the control and cancer =
respectively). Plasma-levels of D.S. and A.S. in Kenyan and British Men The linear regression lines for plasma D.s. and A.s. with age for British men have been included in figs. 1 and 2. These regression lines were calculated from results obtained from assays of the plasma-steroids of 41 normal British men, described in detail elsewhere (Wang et al. 1968). groups,
*
This refers to Central and ethnic groups.
Nyanza Bantu, Nilotic and Nilo-Hamitic