- Email: [email protected]
D-PROPRANOLOL AND ANXIETY
1355 cellular structures. The mutant strain was also more sensitive to a group of hydrazine antidepressants-pheni-
prazine, phenelzine, mebanazine, isocarboxazid, and benzylhydrazine (a metabolite of isocarboxazid)-as well as to
antituberculous hydrazine. In view of these findings, which suggest that certain commonly used hydrazine medicinal agents are capable of altering the D.N.A. of living cells, and because a relationship between reactivity towards D.N.A. and carcinogenic potential has been established, it would seem proper to re-evaluate the potential tumour-inducing ability of hydrazine antidepressants and of isoniazid. Moreover, in the meantime advantage should be taken of the availability of alternative drugs devoid of the hydrazine moiety. These suggestions seem especially appropriate since the agents in question are ! taken over extended periods of time-a situation which conceivably could favour carcinogenesis. I This work was aided by a grant from the Damon Runyon
isoniazid,
some cases of striato-nigral degeneration, which are not easily differentiated from classic idiopathic parkinsonism
before necropsy.
an
Memorial Fund for Cancer Research. H. S. R. is a research career development awardee of the U.S. Public Health Service
(2-K3-GM 29, 024). Department of Microbiology, College of Physicians and Surgeons, HERBERT S. ROSENKRANZ Columbia University, HOWARD S. CARR. New York, N.Y. 10032.
FAILED LEVODOPA THERAPY IN STRIATO-NIGRAL DEGENERATION SIR,-Levodopa was ineffective in two patients with parkinsonism who were found to have striato-nigral
Department of Neurology, Neurological Institute, Kyushu University, Fukuoka 812, Japan.
K. N. T. T. Y.
IZUMI INOUE SHIRABE MlYAZAKI KUROIWA.
D-PROPRANOLOL AND ANXIETY
SiR,-The reported beneficial effect of D-L-propranolol, daily, in anxiety 1,2 has been attributed to the drug’s p-blocking action. This is consistent with the finding that sinus tachycardia in anxious patients is abolished by intravenous administration of the drug.3 p-blockade is largely due to the L-isomer of propranolol; there is little evidence of &bgr;-blockade by the D-form.o1 It is therefore of theoretical, as well as practical, interest to investigate the effect of D-propranolol in anxiety. A pilot study in 10 patients has been completed using a cross-over design and double-blind technique similar to that reported in the earlier papery but with oral administration of D-propranolol 40 mg. four times daily in one treatment period and matching placebo capsules in the other. The Middlesex Hospital questionnaire 6.6 was given to all patients after clinical assessment but before inclusion in the trial (see table) and demonstrated a high level of freefloating anxiety and somatic concomitants.
20 mg. four times
MEAN SCORES ON MIDDLESEX HOSPITAL
QUESTIONNAIRE**
degeneration
at necropsy. Case 1-A 53-year-old man with parkinsonism was severely disabled. The illness had begun 2 years previously. Clinically he showed pronounced bradykinesia and rigidity. There was no tremor. Deep reflexes were normal, but plantar reflexes were extensor bilaterally. Levodopa, in doses up to 6-4 g. daily, was given for 11 months without any response. He died suddenly at home. At necropsy the brain weighed 1180 g. Macroscopic examination showed slight atrophy. Microscopically, the substantia nigra revealed striking lesions in which almost all the melanin-containing cells were absent. Nerve cells were also absent, and gliosis was seen in the putamen bilaterally. Brownish pigmented granules were present in the globus pallidus and subthalamic area. There was mild degeneration of nerve cells in the locus coeruleus and in the Purkinje cells and white matter of the cerebellum. In addition, the corticospinal tracts of the medulla oblongata were pale in sections stained for myelin. The
clinicopathological diagnosis
was
striato-nigral degenera-
tion. Case 2-A 56-year-old woman had parkinsonism with severe disability. Like the other patient she showed pro-
bradykinesia and rigidity but no tremor. Deep hyperactive, and the plantar reflex was equivocally extensor on the left. 2-6 g. of levodopa was given daily, without effect, till her death from pneumonia. The pathological diagnosis was striato-nigral degeneration and olivo-ponto-cerebellar atrophy. Treatment failures with levodopa in parkinsonism have been discussed from many aspects, including drug tolerance,l misdiagnosis,2 concurrent use of pyridoxine,3 and poor absorption.4 The group of patients whose parkinsonism is not improved by levodopa may contain
nounced reflexes
1.
were
Yahr,
M. D. in L-Dopa and Parkinsonism (edited by A. Barbeau and F. H. McDowell); p. 5. Philadelphia, 1970. 2. Markham, C. H. ibid. p. 10. 3. Duvoisin, R. C., Yahr, M. D., Cote, L. D. Trans. Am. neurol. Ass. 1969, 94, 81.
4.
Rivera-Calimlim, L., Dujovne, Bianchine, J. R. Br.
C. A., Morgan, med. J. 1970, iv, 93.
J. P., Lasagna, L.,
Patients
were
matched for age, sex, marital status, and personally events in the trial period.
important life
Random
blood-samples were taken from the patients to plasma levels and to confirm that they were taking medication as prescribed. It is interesting to note that before breaking the code the assessing psychiatrist had strong reservations about one patient’s reliability in taking medication, and subsequently this patient was found to have the lowest plasma level of D-propranolol. Using a closed sequential design the earlier trial1 demonstrated the investigator’s preference for D-L propranolol as the more effective treatment, becoming statistically significant after 15 had completed their treatments. No statistically significant preference for either D-propranolol or placebo became apparent during this pilot study. No preference was expressed by either patient or assessor in 4 cases. Of those who expressed preferences, 2 favoured the first treatment period and 4 the second. In terms of treatment, 4 preferred D-propranolol and 2 placebo. 5 patients reported no side-effects and 2 reported increasing depression during the second period (when they were on placebo). This was judged to be part of their progressing affective disorder and not due to the D-propranolol. Anxiety and depression continued to increase after cessation of the trial. 1 other patient developed vomiting
assess
1. 2. 3.
Granville-Grossman, K., Turner, P. Lancet, 1966, i, 788. Wheatley, D. Br. J. Psychiat. 1969, 115, 1411. Turner, P., Granville-Grossman, K., Smart, J. Lancet, 1965, ii,
4. 5. 6.
Barrett, A. M., Cullum, V. Br. J. Pharmac. 1968, 34, 43. Crown, S., Crisp, A. Br. J. Psychiat. 1966, 112, 917. Crown, S., Duncan, K. P., Howell, R. W. ibid. 1970, 116,
1316.
33.
1356 and
a
second had increased urgency of defalcation while
on
D-propranolol. Another noticed " stomach rumblings while on placebo. In conclusion, the results of this pilot study are consistent with those of Granville-Grossman and Turnery who demonstrated that only autonomically mediated symptoms of anxiety were affected by D-L propranolol. D-propranolol does not have such peripheral autonomic effects. The suggestion that efficacy of propranolol in anxiety is due to peripheral p-blockade rather than a central action is therefore supported. We thank Miss Deborah Hicks, of the department of clinical pharmacology, St. Bartholomew’s Hospital, for estimating the plasma-propranolol levels, and Dr. Paul Bayliss, of Imperial Chemical Industries, for supplying the active and placebo capsules.
Psychological Medicine, and
J. A. BONN PAUL TURNER.
DOWN’S SYNDROME; SEX DIFFERENCE IN RELATION TO MATERNAL AGE SIR,-The letter from Dr. G. P. Largey and Dr. Kathleen Largey (June 12, p. 1242) reports a mean maternal age of female mongoloids (33-28) significantly lower than that for male mongoloids (36-25) in a sample of 74 cases (39
female, 35 male). A comparable result was found in a sample of 89 hospital inpatients with Down’s syndrome (40 female, 49 male)
The mean maternal age of the female 31-55, lower than the mean maternal age of patients the male oatients. which was 34-55. in the Leeds
area.
was
Meanwood Park Hospital, Leeds.
D. A. SPENCER.
DECREASED ANTICOAGULANT TOLERANCE WITH OXYMETHOLONE
SIR,-It has been known for some time that androgens will increase blood fibrinolytic activity 1,2 and that there may be decreased anticoagulant tolerance during therapy with these compounds.We have been involved in a study of the effect of a 17-alkylated anabolic agent, oxymetholone, on the anaemia of patients requiring chronic haemodialysis. Some patients who had been prone to clotting of the indwelling silasticTeflon’ arteriovenous shunt were being maintained on warfarin sodium to stabilise the prothrombin-time at 1-1 times the control value. Therapy with oxymetholone was instituted at 2 mg. per kg. daily. In five patients the prothrombin-time began to rise within 3 months of starting medication. The rise in prothrombintime was accompanied by bleeding episodes in all patients; values returned to normal when oxymetholone was withdrawn. The interaction of these two drugs with resulting hsemorrhagic complications is not at all straightforward. Oxymetholone, in common with all 17-alkylated steroids, may cause transient liver dysfunction which conceivably could affect prothrombin synthesis. Possibly the steroid might affect plasma binding of the warfarin, which could produce a higher circulating titre of warfarin than the dose would suggest. It has been suggested that another androgen, norethandrolone, might potentiate the pharmacological effect of bishydroxycoumarin by increasing the affinity of the receptor site for the anticoagulant,4 and that possibility 1. 2. 3. 4.
avoided by very careful monitoring whenever the these compounds together is considered. Birmingham Hospital, Bordesley Green East, Birmingham B9 5ST.
East
Syntex Pharmaceuticals Ltd., Maidenhead, Berkshire.
use
of
B. H. B. ROBINSON J. B. HAWKINS J. E. ELLIS.
M. MOORE-ROBINSON.
P.A.S.-POSITIVE SUBSTANCE IN LYMPHOCYTES OF PATIENTS WITH CHAGAS’ DISEASE
Academic Department of
Clinical Pharmacology Department, St. Bartholomew’s Hospital, London EC1A 7BE.
should also be considered here. Finally, the possible fibrinolytic effect of oxymetholone would accentuate any bleeding tendency. Whilst the concomitant use of warfarin and oxymetholone is not strictly contraindicated, we feel that attention should be drawn to the potential hazards, and future complications
Fearnley, G. R., Chakrabarti, R. J. clin. Path. 1964, 17, 328. Fearnley, G. R., Chakrabarti, R. Lancet, 1962, ii, 128. Pyorala, K., Kekki, M. Scand. J. clin. Path. 1963, 15, 367. Schrogie, J. J., Solomon, H. M. Clin. Pharmac. Ther. 1967, 8, 70.
SIR,-When I was performing the periodic-acid/Schiff (P.A.S.) reaction 1-4 on smears of peripheral blood from patients with Chagas’ disease I found that a high percentage of lymphocytes showed in their cytoplasm a P.A.s.-positive substance, concentrated in magenta-coloured granules. Other workers have reported 6-7 that normal individuals or patients with various diseases only have a small percentage of peripheral-blood lymphocytes containing P.A.s.-positive material. A relatively high average percentage of such cells has, however, been described in chronic lymphatic leukxmia6 Waldenstrom’s macroglubulinsemia,8 and African trypanosomiasis.7 I have investigated 80 patients with Chagas’ disease (all of whom had Trypanosoma cruzi in the blood and also a positive complement-fixation reaction for Chagas’ disease). In 30 the infection was of recent onset; the other 50 had suffered from Chagas’ disease for a long time. I also studied blood from patients with several diseases but free from Chagas’ disease, chronic lymphatic leukaemia, Waldenstrom’s macroglobulinsemia, or African trypanosomiasis. In addition, blood from 50 normal people was studied. The blood-smears of all groups were fixed in absolute alcohol, treated with 1% periodic acid for 10 minutes, washed in distilled water, and immersed in Schiff reagent (prepared according to the method of Elftman’) for 30 minutes; subsequently they were rinsed in three changes of sulphurous acid. Haematoxylin was used as counterstain. 300 lymphocytes were examined in each bloodfilm. In the smears of all the patients with Chagas’ disease I found high percentages of small and medium-sized
lymphocytes containing P.A.s.-positive substance-average 35% (maximum 67%, minimum 14%). In the groups with other diseases, and the normal people, P.A.s.-positive substance was found in an average of only 2-5% (0-3%9%). The possibility that this P.A.s.-positive substance is liberated into the surrounding medium is strongly suggested by microscopical observations. When smears of blood from the same Chagas’ disease patients were tested with diastase, it was shown that the lymphocytes still contained the P.A.s.-positive substance, which resembled a glycoprotein. The substance may well have an immunological role in 1. MacManus, J. F. A. Nature, 1946, 158, 202. 2. Lillie, R. D., Laskey, A., Greco, J., Jacquier, H. J. Lab. clin. Med. 1947, 32, 910. 3. Hotchkiss, R. D. Archs Biochem. 1948, 16, 131. 4. Lillie, R. D. Anat. Rec. 1950, 108, 239. 5. Wachstein, M. Blood, 1949, 4, 54. 6. Wislocki, G., Rheingold, J., Dempsey, E. ibid. p. 562. 7. Moretti, G., Veiret, U., Broustet, A., Rive, J. C. r. Séanc. Soc. Biol. 1967, 161, 1978. 8. Moretti, G., Veiret, U., Broustet, A. ibid. 1966, 160, 972. 9. Elftman, H. J. Histochem. Cytochem. 1959, 7, 93.
prazine, phenelzine, mebanazine, isocarboxazid, and benzylhydrazine (a metabolite of isocarboxazid)-as well as to
antituberculous hydrazine. In view of these findings, which suggest that certain commonly used hydrazine medicinal agents are capable of altering the D.N.A. of living cells, and because a relationship between reactivity towards D.N.A. and carcinogenic potential has been established, it would seem proper to re-evaluate the potential tumour-inducing ability of hydrazine antidepressants and of isoniazid. Moreover, in the meantime advantage should be taken of the availability of alternative drugs devoid of the hydrazine moiety. These suggestions seem especially appropriate since the agents in question are ! taken over extended periods of time-a situation which conceivably could favour carcinogenesis. I This work was aided by a grant from the Damon Runyon
isoniazid,
some cases of striato-nigral degeneration, which are not easily differentiated from classic idiopathic parkinsonism
before necropsy.
an
Memorial Fund for Cancer Research. H. S. R. is a research career development awardee of the U.S. Public Health Service
(2-K3-GM 29, 024). Department of Microbiology, College of Physicians and Surgeons, HERBERT S. ROSENKRANZ Columbia University, HOWARD S. CARR. New York, N.Y. 10032.
FAILED LEVODOPA THERAPY IN STRIATO-NIGRAL DEGENERATION SIR,-Levodopa was ineffective in two patients with parkinsonism who were found to have striato-nigral
Department of Neurology, Neurological Institute, Kyushu University, Fukuoka 812, Japan.
K. N. T. T. Y.
IZUMI INOUE SHIRABE MlYAZAKI KUROIWA.
D-PROPRANOLOL AND ANXIETY
SiR,-The reported beneficial effect of D-L-propranolol, daily, in anxiety 1,2 has been attributed to the drug’s p-blocking action. This is consistent with the finding that sinus tachycardia in anxious patients is abolished by intravenous administration of the drug.3 p-blockade is largely due to the L-isomer of propranolol; there is little evidence of &bgr;-blockade by the D-form.o1 It is therefore of theoretical, as well as practical, interest to investigate the effect of D-propranolol in anxiety. A pilot study in 10 patients has been completed using a cross-over design and double-blind technique similar to that reported in the earlier papery but with oral administration of D-propranolol 40 mg. four times daily in one treatment period and matching placebo capsules in the other. The Middlesex Hospital questionnaire 6.6 was given to all patients after clinical assessment but before inclusion in the trial (see table) and demonstrated a high level of freefloating anxiety and somatic concomitants.
20 mg. four times
MEAN SCORES ON MIDDLESEX HOSPITAL
QUESTIONNAIRE**
degeneration
at necropsy. Case 1-A 53-year-old man with parkinsonism was severely disabled. The illness had begun 2 years previously. Clinically he showed pronounced bradykinesia and rigidity. There was no tremor. Deep reflexes were normal, but plantar reflexes were extensor bilaterally. Levodopa, in doses up to 6-4 g. daily, was given for 11 months without any response. He died suddenly at home. At necropsy the brain weighed 1180 g. Macroscopic examination showed slight atrophy. Microscopically, the substantia nigra revealed striking lesions in which almost all the melanin-containing cells were absent. Nerve cells were also absent, and gliosis was seen in the putamen bilaterally. Brownish pigmented granules were present in the globus pallidus and subthalamic area. There was mild degeneration of nerve cells in the locus coeruleus and in the Purkinje cells and white matter of the cerebellum. In addition, the corticospinal tracts of the medulla oblongata were pale in sections stained for myelin. The
clinicopathological diagnosis
was
striato-nigral degenera-
tion. Case 2-A 56-year-old woman had parkinsonism with severe disability. Like the other patient she showed pro-
bradykinesia and rigidity but no tremor. Deep hyperactive, and the plantar reflex was equivocally extensor on the left. 2-6 g. of levodopa was given daily, without effect, till her death from pneumonia. The pathological diagnosis was striato-nigral degeneration and olivo-ponto-cerebellar atrophy. Treatment failures with levodopa in parkinsonism have been discussed from many aspects, including drug tolerance,l misdiagnosis,2 concurrent use of pyridoxine,3 and poor absorption.4 The group of patients whose parkinsonism is not improved by levodopa may contain
nounced reflexes
1.
were
Yahr,
M. D. in L-Dopa and Parkinsonism (edited by A. Barbeau and F. H. McDowell); p. 5. Philadelphia, 1970. 2. Markham, C. H. ibid. p. 10. 3. Duvoisin, R. C., Yahr, M. D., Cote, L. D. Trans. Am. neurol. Ass. 1969, 94, 81.
4.
Rivera-Calimlim, L., Dujovne, Bianchine, J. R. Br.
C. A., Morgan, med. J. 1970, iv, 93.
J. P., Lasagna, L.,
Patients
were
matched for age, sex, marital status, and personally events in the trial period.
important life
Random
blood-samples were taken from the patients to plasma levels and to confirm that they were taking medication as prescribed. It is interesting to note that before breaking the code the assessing psychiatrist had strong reservations about one patient’s reliability in taking medication, and subsequently this patient was found to have the lowest plasma level of D-propranolol. Using a closed sequential design the earlier trial1 demonstrated the investigator’s preference for D-L propranolol as the more effective treatment, becoming statistically significant after 15 had completed their treatments. No statistically significant preference for either D-propranolol or placebo became apparent during this pilot study. No preference was expressed by either patient or assessor in 4 cases. Of those who expressed preferences, 2 favoured the first treatment period and 4 the second. In terms of treatment, 4 preferred D-propranolol and 2 placebo. 5 patients reported no side-effects and 2 reported increasing depression during the second period (when they were on placebo). This was judged to be part of their progressing affective disorder and not due to the D-propranolol. Anxiety and depression continued to increase after cessation of the trial. 1 other patient developed vomiting
assess
1. 2. 3.
Granville-Grossman, K., Turner, P. Lancet, 1966, i, 788. Wheatley, D. Br. J. Psychiat. 1969, 115, 1411. Turner, P., Granville-Grossman, K., Smart, J. Lancet, 1965, ii,
4. 5. 6.
Barrett, A. M., Cullum, V. Br. J. Pharmac. 1968, 34, 43. Crown, S., Crisp, A. Br. J. Psychiat. 1966, 112, 917. Crown, S., Duncan, K. P., Howell, R. W. ibid. 1970, 116,
1316.
33.
1356 and
a
second had increased urgency of defalcation while
on
D-propranolol. Another noticed " stomach rumblings while on placebo. In conclusion, the results of this pilot study are consistent with those of Granville-Grossman and Turnery who demonstrated that only autonomically mediated symptoms of anxiety were affected by D-L propranolol. D-propranolol does not have such peripheral autonomic effects. The suggestion that efficacy of propranolol in anxiety is due to peripheral p-blockade rather than a central action is therefore supported. We thank Miss Deborah Hicks, of the department of clinical pharmacology, St. Bartholomew’s Hospital, for estimating the plasma-propranolol levels, and Dr. Paul Bayliss, of Imperial Chemical Industries, for supplying the active and placebo capsules.
Psychological Medicine, and
J. A. BONN PAUL TURNER.
DOWN’S SYNDROME; SEX DIFFERENCE IN RELATION TO MATERNAL AGE SIR,-The letter from Dr. G. P. Largey and Dr. Kathleen Largey (June 12, p. 1242) reports a mean maternal age of female mongoloids (33-28) significantly lower than that for male mongoloids (36-25) in a sample of 74 cases (39
female, 35 male). A comparable result was found in a sample of 89 hospital inpatients with Down’s syndrome (40 female, 49 male)
The mean maternal age of the female 31-55, lower than the mean maternal age of patients the male oatients. which was 34-55. in the Leeds
area.
was
Meanwood Park Hospital, Leeds.
D. A. SPENCER.
DECREASED ANTICOAGULANT TOLERANCE WITH OXYMETHOLONE
SIR,-It has been known for some time that androgens will increase blood fibrinolytic activity 1,2 and that there may be decreased anticoagulant tolerance during therapy with these compounds.We have been involved in a study of the effect of a 17-alkylated anabolic agent, oxymetholone, on the anaemia of patients requiring chronic haemodialysis. Some patients who had been prone to clotting of the indwelling silasticTeflon’ arteriovenous shunt were being maintained on warfarin sodium to stabilise the prothrombin-time at 1-1 times the control value. Therapy with oxymetholone was instituted at 2 mg. per kg. daily. In five patients the prothrombin-time began to rise within 3 months of starting medication. The rise in prothrombintime was accompanied by bleeding episodes in all patients; values returned to normal when oxymetholone was withdrawn. The interaction of these two drugs with resulting hsemorrhagic complications is not at all straightforward. Oxymetholone, in common with all 17-alkylated steroids, may cause transient liver dysfunction which conceivably could affect prothrombin synthesis. Possibly the steroid might affect plasma binding of the warfarin, which could produce a higher circulating titre of warfarin than the dose would suggest. It has been suggested that another androgen, norethandrolone, might potentiate the pharmacological effect of bishydroxycoumarin by increasing the affinity of the receptor site for the anticoagulant,4 and that possibility 1. 2. 3. 4.
avoided by very careful monitoring whenever the these compounds together is considered. Birmingham Hospital, Bordesley Green East, Birmingham B9 5ST.
East
Syntex Pharmaceuticals Ltd., Maidenhead, Berkshire.
use
of
B. H. B. ROBINSON J. B. HAWKINS J. E. ELLIS.
M. MOORE-ROBINSON.
P.A.S.-POSITIVE SUBSTANCE IN LYMPHOCYTES OF PATIENTS WITH CHAGAS’ DISEASE
Academic Department of
Clinical Pharmacology Department, St. Bartholomew’s Hospital, London EC1A 7BE.
should also be considered here. Finally, the possible fibrinolytic effect of oxymetholone would accentuate any bleeding tendency. Whilst the concomitant use of warfarin and oxymetholone is not strictly contraindicated, we feel that attention should be drawn to the potential hazards, and future complications
Fearnley, G. R., Chakrabarti, R. J. clin. Path. 1964, 17, 328. Fearnley, G. R., Chakrabarti, R. Lancet, 1962, ii, 128. Pyorala, K., Kekki, M. Scand. J. clin. Path. 1963, 15, 367. Schrogie, J. J., Solomon, H. M. Clin. Pharmac. Ther. 1967, 8, 70.
SIR,-When I was performing the periodic-acid/Schiff (P.A.S.) reaction 1-4 on smears of peripheral blood from patients with Chagas’ disease I found that a high percentage of lymphocytes showed in their cytoplasm a P.A.s.-positive substance, concentrated in magenta-coloured granules. Other workers have reported 6-7 that normal individuals or patients with various diseases only have a small percentage of peripheral-blood lymphocytes containing P.A.s.-positive material. A relatively high average percentage of such cells has, however, been described in chronic lymphatic leukxmia6 Waldenstrom’s macroglubulinsemia,8 and African trypanosomiasis.7 I have investigated 80 patients with Chagas’ disease (all of whom had Trypanosoma cruzi in the blood and also a positive complement-fixation reaction for Chagas’ disease). In 30 the infection was of recent onset; the other 50 had suffered from Chagas’ disease for a long time. I also studied blood from patients with several diseases but free from Chagas’ disease, chronic lymphatic leukaemia, Waldenstrom’s macroglobulinsemia, or African trypanosomiasis. In addition, blood from 50 normal people was studied. The blood-smears of all groups were fixed in absolute alcohol, treated with 1% periodic acid for 10 minutes, washed in distilled water, and immersed in Schiff reagent (prepared according to the method of Elftman’) for 30 minutes; subsequently they were rinsed in three changes of sulphurous acid. Haematoxylin was used as counterstain. 300 lymphocytes were examined in each bloodfilm. In the smears of all the patients with Chagas’ disease I found high percentages of small and medium-sized
lymphocytes containing P.A.s.-positive substance-average 35% (maximum 67%, minimum 14%). In the groups with other diseases, and the normal people, P.A.s.-positive substance was found in an average of only 2-5% (0-3%9%). The possibility that this P.A.s.-positive substance is liberated into the surrounding medium is strongly suggested by microscopical observations. When smears of blood from the same Chagas’ disease patients were tested with diastase, it was shown that the lymphocytes still contained the P.A.s.-positive substance, which resembled a glycoprotein. The substance may well have an immunological role in 1. MacManus, J. F. A. Nature, 1946, 158, 202. 2. Lillie, R. D., Laskey, A., Greco, J., Jacquier, H. J. Lab. clin. Med. 1947, 32, 910. 3. Hotchkiss, R. D. Archs Biochem. 1948, 16, 131. 4. Lillie, R. D. Anat. Rec. 1950, 108, 239. 5. Wachstein, M. Blood, 1949, 4, 54. 6. Wislocki, G., Rheingold, J., Dempsey, E. ibid. p. 562. 7. Moretti, G., Veiret, U., Broustet, A., Rive, J. C. r. Séanc. Soc. Biol. 1967, 161, 1978. 8. Moretti, G., Veiret, U., Broustet, A. ibid. 1966, 160, 972. 9. Elftman, H. J. Histochem. Cytochem. 1959, 7, 93.