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CORYNEBACTERIUM PARVUM AND ANÆSTHETICS
914 neonatal clinical assessment in a much larger series could well reveal impaired neurological function from excessive bilirubin staining of nerve-cells, and prolonged feeding disturbances in the premature baby, due to immature neuromuscular function at sphincters such as the pyloric, leading to excessive use of drugs (e.g., dicyclonineMer-
bentyl ’). without toxaemia or cephalopelvic of meconium-stained liquor is restricted umbilical-cord circulation and it is not necessary to presume placental failure. Repercussions to this article can be too serious not to question its validity. An unbiased opinion on its results could assert that at best nothing is gained from interruption of normal pregnancy at 39 weeks, but the paper does not explore immediate and late prognoses-mental and physical-for the infant. It must also be asked if there is any evidence to refute that in normal pregnancy and for a healthy child the fetus and mother play a vital part in deciding when the fetus is ready for a separate existence. Finally, since it is in obstetrically normal patients that premature induction of labour is advocated, there will be many expectant mothers who will resent this unsolicited interference and feel distressed at being denied the fulfilment of natural childbirth. In the normal
disproportion,
a
patient, major
Mothers’ Hospital, London E5.
cause
D. J. MACRAE.
CORYNEBACTERIUM PARVUM AND ANÆSTHETICS Mosedale and Mr Smith (Jan. 18, p. 168) Sm.—Mrs treated that mice report intravenously with Corynebacterium parvum (c.P.) show enhanced sensitivity to pentobarbitone and tribromoethanol. We wish to describe our experience with this adjuvant. We have observed that hepatic microsomal preparations from Sprague-Dawley rats given c.P. (10 mg. per sq. m.) intravenously show strikingly reduced ability to metabolise standard substrates such as aniline and aminopyrine. Maximum inhibition (50-60%) of enzyme activity occurs 3-6 days after adjuvant administration and is followed by a slow recovery period of 9-12 days. Pentobarbitone-induced sleeping-times in c.p.-treated rats are increased over 100% on day 6 after C.P. Control rats were injected with 0-2 ml. of-001% merthiolate solution corresponding to the amount of merthiolate in the c.P. dosage without any of the above changes. These results indicate impairment of the hepatic microsomal drug-metabolising enzyme system. Apart from marginal ( < 20 °o ) enlargement, livers of c.p.-treated rats show no gross morphological abnormalities. Histological examina tion reveals scattered granulomatous lesions and infiltration of the portal fields by lymphohistiocytes but no parenchymal cell damage or zonal degeneration. We wish to emphasise that the c.p. dosage chosen (10 mg. per sq. m.) was much smaller than that conventionally used in animal studies (c. 100 mg. per sq. m.)1 in order to approximate closely dosages in man (5-10 mg. per sq. m.).11We have previously reported 3 similar findings in rats treated intravenously with B.C.G. Inhibition of hepatic microsomal enzymes might therefore be a common effect of bacterial
currently under investigation in our laboratories. The results of these studies will be published subsequently. are
University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77025, U.S.A.
pharmacological properties of most antitumour drugs greatly modified by hepatic metabolism, these observations have important therapeutic and toxicological implications for patients undergoing chemoimmunotherapy. The effects of c.p. therapy on the clinical pharmacology of D.I.C. (NSC-45388), cyclophosphamide, and adriamycin are
Scott, M. T. Semin. Oncol. 1974, 1, 367. Reed, R. Symposium on Immunological Reactions to Melanoma Antigens, Hanover, West Germany (in the press). 3. Farquhar, D. Proc. Am. Ass. Cancer Res. 1974, 15, 128.
1. 2.
TI LI Loo R. REED M. LUNA.
AGE-RELATED CHANGES IN T AND B CELLS SrR,—Diaz-Jouanen and others (March 22, p. 688) suggest that failure to record " null " cells (those with neither " B nor " T " markers) accounts for some of the discrepancies between the findings of different groups studying age-related variations in circulating B and T cell markers. This must certainly be an important factor if null cells are as common as Diaz-Jouanen et al. report. Their figures are, however, at variance with many published data. They find a similar percentage of lymphocytes bearing surface immunoglobulin (a B-cell marker) in preparations from cord blood and from healthy adults (22-23%), whereas others have reported an increase in the proportion, as well as absolute number, of surface-Ig-positive cells in cord blood.1,22 In immunofluorescence studies using a U/V microscope with Ploem’s incident illumination, we find that some 30-40% of cord-blood mononuclear cells have surface immunoglobulin-a figure which agrees well with other recent findings in infants aged 4-12 months3 and in cord-blood samples.4 Diaz-Jouanen et al. report a mean value for cord lymphocytes forming spontaneous rosettes with sheep erythrocytes (a T-cell marker) of only 35%. This contrasts with our figure of 53%.5S The difference is even greater than it appears since Diaz-Jouanen et al. express their results as percentages of total lymphocytes only, while we express ours as percentages of total mononuclear cells, making no attempt to exclude or identify the estimated 10% of monocytes in the cell suspension. 6,7 In examining mononuclear-cell suspensions from the blood of healthy adults by combined immunofluorescence (for surface Ig) and the sheep-cell rosette test, we obtain results in very close agreement with other published studies.6-10Approximately 2% of cells have both markers and only some 10-15% have neither. Most of these null cells we take to be monocytes.11 The proportion of null cells has not been increased in the few cord-blood samples we have studied with the double-marker system. It has been shown that under appropriate conditions virtually all blood lymphocytes bearing T-cell-specific surface antigen (demonstrated by immunofluorescence) will’ also form rosettes with sheep erythrocytes. 6,7, 111 There were, however, striking discrepancies between the two tests as applied by Diaz-Jouanen et al. It is of considerable interest that, from their data, the efficiency of rosette formation by T lymphocytes appears to be inversely related to the donor’s age and this phenomenon will warrant further study when details of their techniques are "
published. 1. 2. 3.
adjuvants. Since the
D. FARQUHAR
4.
Papamichail, M., Brown, J. C., Holborow, E. J. Lancet, 1971, ii, 850. Froland, S. S., Natvig, J. B. Clin. exp. Immun. 1972, 11, 495. Gajl-Peczalska, K. J., Hallgren, H., Kersey, J. H., Zusman, J., Yunis, E. J. Lancet, 1974, ii, 163. Campbell, A. C., Waller, C., Wood, J., Aynsley-Green, A., Yu, V.
Clin. exp. Immun. 1974, 18, 461. Smith, M. A., Evans, J., Steel, C. M. ibid. p. 922. Aiuti, F., et al. Scand. J. Immun. 1974, 3, 521. Brown, G., Greaves, M. F. ibid. p. 161. Bentwich, Z., Douglas, S. D., Skutelsky, E., Kunkel, H. G. J. exp. Med. 1973, 137, 1532. 9. Kaplan, M. E., Clark, C. J. immun. Meth. 1974, 5, 131. 10. Dickler, H. B., Adkinson, N. F., Terrey, W. D. Nature, 1974, 247, 5. 6. 7. 8.
213. 11. 12.
Evans, J., Smith, M. A., Steel, C. M. J. immun. Meth. (in the press). Kersey, J. H., Sabad, A., Gajl-Peczalska, K. J., Hallgren, H. M., Yunis, E. J., Nesbit, M. E. Science, 1973, 182, 1355.
bentyl ’). without toxaemia or cephalopelvic of meconium-stained liquor is restricted umbilical-cord circulation and it is not necessary to presume placental failure. Repercussions to this article can be too serious not to question its validity. An unbiased opinion on its results could assert that at best nothing is gained from interruption of normal pregnancy at 39 weeks, but the paper does not explore immediate and late prognoses-mental and physical-for the infant. It must also be asked if there is any evidence to refute that in normal pregnancy and for a healthy child the fetus and mother play a vital part in deciding when the fetus is ready for a separate existence. Finally, since it is in obstetrically normal patients that premature induction of labour is advocated, there will be many expectant mothers who will resent this unsolicited interference and feel distressed at being denied the fulfilment of natural childbirth. In the normal
disproportion,
a
patient, major
Mothers’ Hospital, London E5.
cause
D. J. MACRAE.
CORYNEBACTERIUM PARVUM AND ANÆSTHETICS Mosedale and Mr Smith (Jan. 18, p. 168) Sm.—Mrs treated that mice report intravenously with Corynebacterium parvum (c.P.) show enhanced sensitivity to pentobarbitone and tribromoethanol. We wish to describe our experience with this adjuvant. We have observed that hepatic microsomal preparations from Sprague-Dawley rats given c.P. (10 mg. per sq. m.) intravenously show strikingly reduced ability to metabolise standard substrates such as aniline and aminopyrine. Maximum inhibition (50-60%) of enzyme activity occurs 3-6 days after adjuvant administration and is followed by a slow recovery period of 9-12 days. Pentobarbitone-induced sleeping-times in c.p.-treated rats are increased over 100% on day 6 after C.P. Control rats were injected with 0-2 ml. of-001% merthiolate solution corresponding to the amount of merthiolate in the c.P. dosage without any of the above changes. These results indicate impairment of the hepatic microsomal drug-metabolising enzyme system. Apart from marginal ( < 20 °o ) enlargement, livers of c.p.-treated rats show no gross morphological abnormalities. Histological examina tion reveals scattered granulomatous lesions and infiltration of the portal fields by lymphohistiocytes but no parenchymal cell damage or zonal degeneration. We wish to emphasise that the c.p. dosage chosen (10 mg. per sq. m.) was much smaller than that conventionally used in animal studies (c. 100 mg. per sq. m.)1 in order to approximate closely dosages in man (5-10 mg. per sq. m.).11We have previously reported 3 similar findings in rats treated intravenously with B.C.G. Inhibition of hepatic microsomal enzymes might therefore be a common effect of bacterial
currently under investigation in our laboratories. The results of these studies will be published subsequently. are
University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77025, U.S.A.
pharmacological properties of most antitumour drugs greatly modified by hepatic metabolism, these observations have important therapeutic and toxicological implications for patients undergoing chemoimmunotherapy. The effects of c.p. therapy on the clinical pharmacology of D.I.C. (NSC-45388), cyclophosphamide, and adriamycin are
Scott, M. T. Semin. Oncol. 1974, 1, 367. Reed, R. Symposium on Immunological Reactions to Melanoma Antigens, Hanover, West Germany (in the press). 3. Farquhar, D. Proc. Am. Ass. Cancer Res. 1974, 15, 128.
1. 2.
TI LI Loo R. REED M. LUNA.
AGE-RELATED CHANGES IN T AND B CELLS SrR,—Diaz-Jouanen and others (March 22, p. 688) suggest that failure to record " null " cells (those with neither " B nor " T " markers) accounts for some of the discrepancies between the findings of different groups studying age-related variations in circulating B and T cell markers. This must certainly be an important factor if null cells are as common as Diaz-Jouanen et al. report. Their figures are, however, at variance with many published data. They find a similar percentage of lymphocytes bearing surface immunoglobulin (a B-cell marker) in preparations from cord blood and from healthy adults (22-23%), whereas others have reported an increase in the proportion, as well as absolute number, of surface-Ig-positive cells in cord blood.1,22 In immunofluorescence studies using a U/V microscope with Ploem’s incident illumination, we find that some 30-40% of cord-blood mononuclear cells have surface immunoglobulin-a figure which agrees well with other recent findings in infants aged 4-12 months3 and in cord-blood samples.4 Diaz-Jouanen et al. report a mean value for cord lymphocytes forming spontaneous rosettes with sheep erythrocytes (a T-cell marker) of only 35%. This contrasts with our figure of 53%.5S The difference is even greater than it appears since Diaz-Jouanen et al. express their results as percentages of total lymphocytes only, while we express ours as percentages of total mononuclear cells, making no attempt to exclude or identify the estimated 10% of monocytes in the cell suspension. 6,7 In examining mononuclear-cell suspensions from the blood of healthy adults by combined immunofluorescence (for surface Ig) and the sheep-cell rosette test, we obtain results in very close agreement with other published studies.6-10Approximately 2% of cells have both markers and only some 10-15% have neither. Most of these null cells we take to be monocytes.11 The proportion of null cells has not been increased in the few cord-blood samples we have studied with the double-marker system. It has been shown that under appropriate conditions virtually all blood lymphocytes bearing T-cell-specific surface antigen (demonstrated by immunofluorescence) will’ also form rosettes with sheep erythrocytes. 6,7, 111 There were, however, striking discrepancies between the two tests as applied by Diaz-Jouanen et al. It is of considerable interest that, from their data, the efficiency of rosette formation by T lymphocytes appears to be inversely related to the donor’s age and this phenomenon will warrant further study when details of their techniques are "
published. 1. 2. 3.
adjuvants. Since the
D. FARQUHAR
4.
Papamichail, M., Brown, J. C., Holborow, E. J. Lancet, 1971, ii, 850. Froland, S. S., Natvig, J. B. Clin. exp. Immun. 1972, 11, 495. Gajl-Peczalska, K. J., Hallgren, H., Kersey, J. H., Zusman, J., Yunis, E. J. Lancet, 1974, ii, 163. Campbell, A. C., Waller, C., Wood, J., Aynsley-Green, A., Yu, V.
Clin. exp. Immun. 1974, 18, 461. Smith, M. A., Evans, J., Steel, C. M. ibid. p. 922. Aiuti, F., et al. Scand. J. Immun. 1974, 3, 521. Brown, G., Greaves, M. F. ibid. p. 161. Bentwich, Z., Douglas, S. D., Skutelsky, E., Kunkel, H. G. J. exp. Med. 1973, 137, 1532. 9. Kaplan, M. E., Clark, C. J. immun. Meth. 1974, 5, 131. 10. Dickler, H. B., Adkinson, N. F., Terrey, W. D. Nature, 1974, 247, 5. 6. 7. 8.
213. 11. 12.
Evans, J., Smith, M. A., Steel, C. M. J. immun. Meth. (in the press). Kersey, J. H., Sabad, A., Gajl-Peczalska, K. J., Hallgren, H. M., Yunis, E. J., Nesbit, M. E. Science, 1973, 182, 1355.