994 13’1-radiation damage (although the time course is unusually early for this mechanism alone); underlying autoimmune thyroiditis5 (antimicrosomal antibody titre was 1/2560); transiently suppressed T.S.H. after thyrotoxicosis6; or extreme sensitivity to exogenous iodides as in diffuse toxic goitre after radioiodine 7(although the patients with this condition were euthyroid before taking iodides, and had no recurrent hyperthyroidism after iodides were stopped). Propranolol probably cannot
be
incriminated, since several reports indicate that dur-
ing propranolol therapy for thyrotoxicosis, thyroxine levels either increase slightly or remain unchanged. 10.11 Since thyroidal secretory activity may spontaneously resume and evolve into thyrotoxicosis after transient post-’3’I hypothyroidism, it is wise to allow an interval of observation before starting exogenous thyroid-hormone replacement in this un-
the peroxidase-counts the plasma-cells were also counted in sections stained by methyl-green/pyronin (first biopsy 643±226, second biopsy 260±57). The increase in all classes of Ig in the first biopsy specimen indicated a polyclonal, and therefore not neoplastic, response; the figures for the second biopsy were all normal. This case shows that giardiasis can produce severe atrophy of the jejunal mucosa with a dense plasma-cell infiltrate without underlying disease and with complete recovery after treaton
ment.
Departments of Pathology St. Mary’s Hospital, London W2
and
Gastro-enterology,
W. K. BLENKINSOPP J. A. GIBSON G. P. HAFFENDEN
usual context. Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Pennsylvania 17033, U.S.A.
ELISA FOR RHEUMATOID FACTOR
J.
D. VELDHUIS
GIARDIASIS AND SEVERE JEJUNAL ABNORMALITY
SIR,-Malabsorption occurs in some patients with Giardia lamblia infection of the small gut; it was found in 29 of 40 patients with symptoms due to giardiasis.’ In symptomatic cases the jejunal mucosa usually shows a mild or moderate abnormality of architecture.2 We have seen a patient in whom jejunal biopsy revealed a heavy infection with G. lamblia, severe partial villous atrophy, and a dense plasma-cell infiltrate of the lamina propria; the changes were sufficient to warrant biopsy after treatment to establish that there was no underlying disease. This 65-year-old woman had had watery diarrhoea 3 weeks after returning to England from a 2-week tour of the Far East. 14 weeks after her return she had lost some 3 kg in weight and had obvious pitting oedema of both ankles with a normal jugular venous pressure. Her haemoglobin, white-cell count, eosinophil-count, and st;rum-vitamin-BI2 were normal; her mean corpuscular volume was 100-103 fl; the bone-marrow showed no megaloblasts, but part 1 of the Schilling test gave an abnormal result (6.2% of loading dose excreted). Serum-albumin (26-36 g/1) was low, fsecal fat excretion was 34.7and 48.7mmol/24 h (normal less than 18), and a xylose-tolerance test gave an equivocal result. Six stool specimens examined for parasites were negative, and barium studies were normal. No parasites were found in the jejunal aspirate, but jejunal biopsy showed the changes described above. The patient was given a 7-day course of metronidazole (200 mg three times a day), whereupon her diarrhoea ceased, and over the subsequent 4 months her weight and laboratory findings returned to normal; jejunal biopsy 8 weeks after treatment showed a normal mucosa. Plasma cells were identified by the peroxidase-antiperoxidase method in 5 µm paraffin sections of the formalin-fixed tissue and counted in the lamina propria overlying a unit length of muscularis mucosx. Mean values (±s.D.)/mm muscularis mucosa were, at the first biopsy, IgA 466+140, IgM 94±43, IgG 180±114 (total 740); and at the repeat biopsy they were IgA 180±54, IgM 49+17, IgG 11+9 (total 240). As a check 5. Irvine, W. J., Gray, R. S., Morris, P. J., Ting, A. Lancet, 1977, i, 898. 6. Toft, A. D., Seth, J., Hunter, W. M., Irvine, W. J. ibid. 1974, i, 704. 7. Braverman, L. E., Woeber, R. A., Ingbar, S. H. New Engl. J. Med.
1969, 281, 816. 8. Utiger, R. D. ibid. 1972, 287, 562. 9. Braverman, L. E., Ingbar, S. H., Vagenakis, A. G. J. clin. Endocr. Metab. 1971, 32, 515. 10. Harrower, A. D. B., Fyffe, J. A., Horn, D. B., Strong, J. A. Clin. Endocr. 1977, 7, 41. 11. Lotti, G., Delitala, G., Devilla, L. ibid. 1977, 6, 405. 1. Wright, S. G., Tomkins, A. M., Ridley, D. S. Gut, 1977, 18, 343. 2. Thompson, A., Rowland, R., Hecker, R., Gibson, G. E., Reid, D. P. J. clin. Path. 1977, 30, 292.
SIR,-Early detection of rheumatoid factor may have prognostic value for patients with rheumatoid arthritis. Diagnostic tests such as latex fixation (Singer and Plotz) and sheepcell agglutination (Rose-Waaler) may exhibit some lack of specificity and sensitivity. The enzyme-linked immunosorbent assay (ELISA) may be a very sensitive test for detection of antigens and antibodies.’ We have used ELISA to investigate specificity, sensitivity, and reproducibility of this assay system for detection of rheumatoid factor. Flatbottom microtitre plates (Dynatech M129A) were coated with rabbit IgG (1 mg/dl) according to the method described by Voller et a1.2 Two-fold dilutions of serum were assayed with a solid-phase indirect technique with goat antihuman IgM peroxidase. The amount of fixed peroxidase was determined with 5-aminosalicylic acid and hydrogen peroxide as substrate. Sera from 132 patients submitted for rheumatoid-factor testing were investigated. 93 sera were latex-fixation positive and 39 were negative. All sera were further tested by Rose-Waaler microtitre assay with sheep erythrocytes sensitised with rabbit antisheep IgG and by ELISA. Preliminary studies proved that ELISA was 3 times more sensitive than the Rose-Waaler test. Sera with titres at or below 1/50 in ELISA were considered negative, compared with titres 1/16 in the Rose-Waaler test:
The coefficient of correlation was 84%. Only 5 out of the 18 latex-positive sera were scored as strong reactive. All 18 sera were negative in the Rose-Waaler test and in a quantitative latex-fixation assay (1/40). This finding may be caused by the fact that the latex-fixation test, although more sensitive, is less diagnostically specific. The 3 latex-fixation negative, ELISApositive sera were 1/100 reactive in ELISA, and 2 sera scored 1/32 and 1/64 in the Rose-Waaler test. A comparison between the diagnostically more specific RoseWaaler test and ELISA gave the following results: -
The coefficient of correlation of this test was 93%. Only 1 out of the 10 Rose-Waaler negative ELISA positives (titre 100-400) proved to be latex-fixation negative. The reproducibility and sensitivity of ELISA in repeated tests were better than those for the Rose-Waaler test. Furthermore spectrophotometric readings of the results can be made, and this is under investigation. The specificity of the ELISA test was further investigated. 40 sera from patients positive for streptolysin, brucella, sal1. Engvall, E., Perlmann, P. J. Immun. 1972, 109, 129. 2. Voller, A., and others Bull. Wld Hlth Org. 1976, 53, 55.
995
monella, or gonococcal antibodies or infectious mononucleosis proved to be negative in the ELISA test. ELISA can be used as a specific, sensitive, and reproducible assay of rheumatoid factor. However, further standardisation is necessary.
as
for
most ELISA
tests,
Department of Medical Microbiology, Institute Medical Laboratories and Ignatius Hospital, Breda, Netherlands
F. TH. C. WILLEMS C. C. M. KLAASSEN DE KORT
since they may have no further seizures. Case 3 is now classified correctly, but he was incorrectly classified at his school medical. Although only a very small sample, these cases raise a number of questions: are c.M.o.s properly trained to make these very important decisions; are equally inappropriate restrictions being applied to children with other chronic conditions ; and should not the medical records of all children be reviewed just before they leave school, because their state of health may have changed? I thank Dr R. Wilson and Dr M.
Roxby
for advice and encourage-
ment.
EPILEPSY AND THE SCHOOL LEAVER’S MEDICAL
SiR,--One of the duties of a clinical medical officer (c.M.o.) is the medical examination of pupils in their last year of comeducation. This is the last routine school medical examination the adolescent will have even though he or she may stay on for two years or more. The c.M.o. has to decide if the school leaver’s subsequent employment should be restricted in any way. Any restrictions are entered on a special form (Y9). Where a pupil has or has had a chronic illness the decision can be difficult. If restrictions are enforced the adolescent may find some forms of employment closed to him, so the decision is important. Problems often arise with epilepsy, and I decided to review the records of children labelled as epileptic in the borough in which I was working. Of 20 281 children in ordinary State schools, 49 were labelled as epileptic, and 7 of these had had school leavers’ medicals:
for Sick Children, London WC1N 3JH
Hospital
DAVID ELLIMAN
pulsory
Case 1.-Girl of 17. Nocturnal seizures between the ages of 12y and 13. Since her first seizure she had been on continuous anticonvulsants. School leavers’ medical at age 15. Case 2.-Boy of 16. One seizure at age 12 in association with rubella encephalitis. Since then he has been on anticonvulsants continuously. At the time of his school leavers’ medical (age 16y) he was being weaned off them. Case 3.-Boy of 16. Two seizures in association with encephalitis at age 9 years. He had been on continuous medication until, after slow reduction, this was stopped very recently. School leavers’ medical at age 15, before anticonvulsants were tapered off. Case 4.-Boy of 16. Seizures at age 8 and 12. Since the second seizure he has been on continuous medication and is seizure-free. School leavers’ medical at age 15. Case 5.-Girl of 16 who started having "funny turns" at age 7. She was put on anticonvulsants. At age 14 medication was stopped and it was decided the "turns" had been fainting episodes rather than seizures. At a school leavers’ medical when 16 years old, she had been free of "turns" and off medication for 2 years. Case 6.-Boy of 15 2. Started having seizures when aged 10 and is now fairly well-controlled on medication though he still has occasional seizures. School leavers’ medical at 15 2 Case 7.-Boy of 16 who had his only seizure at age lly. He had been on medication from then until it was discontinued at about age 15. He has had no further seizures and his school leavers’ medical was done at age 15(9 months after treatment stopped).
On the Y9s of all these pupils except case 7 the c.M.o. had stated: "In my opinion this pupil is not suitable for work at heights or near vehicles in action". Leaving aside the question of the original diagnosis and treatment, at the time of their medicals all but cases 2 and 7 would have been legally entitled to a full driver’s licence (assuming they were old enough and had no other disabilities). Logically therefore, any employment restrictions in cases 1, 3, 4, 5, and 6 might not seem justifiable. Case 2 would not be eligible for a licence so some restrictions might be iri order. Case 3 would not now be eligible for a drivers’ licence and so, while restrictions may not have been justifiable at the time of his medical, they would now. As case 7 had been off treatment for only 9 months before his medical, restrictions could well be
On the
StR,—The results described by Dr Millar Craig and his colp. 797) are not only of practical but also of theoretical interest. The enormous fall of arterial presgreat sure during sleep was a great surprise to us when we first observed it using the first fully automatic apparatus for recording arterial pressure in the absence of an observer.’ The size of the fall was amply confirmed when we used Dr Stott’s improved apparatus,2 also used by Millar Craig and others. (Why did they not refer to the earlier paper whose results they confirmed ?) The cardiovascular changes during sleep were analysed by my colleagues.3 They are usually attributed to the change in the activity of the reticular formation in the brain. Have Millar Craig and his colleagues plotted blood-pressure and pulse together on the same graph? If so, did the changes parallel one another? They should have, if they severally reflect the activity of the reticular formation.
leagues (April 15,
5 Horwood Close,
Headington, Oxford OX3 7RF
criterion of
eligibility for a drivers’ licence being unfairly restricted; case 7 should, perhaps have some restrictions imposed but has not; and cases 2, 3, and 6 are justifiably restricted. However, cases 2 and 7 should be reviewed 2 years after medication has been stopped simple
1, 4, and 5
were
GEORGE PICKERING
SiR,—We have demonstrated4-6 that the most important determinants of blood-pressure variability over a 24 h period are physical activity and sleep. We were therefore surprised that Dr Millar Craig and his colleagues did not seem to take physical activity into sufficient account in their analysis of changes in blood-pressure in the early morning. From their grouped data it is impossible to determine when their patients awoke; in our experience such patients often awaken early in the morning, and it is inconceivable that they would all awaken simultaneously. We found no significant rise in bloodpressure before awakening, but we did find that, after awakening, pressure rises but is further affected by physical activity. The figure represents group data on eighteen patients (average age 40, range 21-58) who had continuous intra-arterial blood pressure recorded over 24 h.7 Casual blood-pressure averaged 150/96 mm Hg (range 120/70 to 230/120) and all were untreated at the time of study. To clarify the influence of sleep and awakening we determined the time at which each patient woke and used that as our reference point. Blood-pressure was then averaged over 30 min periods backwards throughout 1.
D. W., Honour, A. J., Fenton, G. W., Stott, F. W., Pickering, G. W. Clin. Sci., 1964, 26, 445. 2. Bevan, A. T., Honour, A. J., Stott, F. H. ibid, 1969 36, 329. 3. Bristow, J. D., Honour, A. J., Pickering, T. G., Sleight, P. Cardiovasc. Res.
Richardson,
1969, 3, 476. Littler, W. A., Honour, A. J., Carter, R. D., Sleight, P. Br. med. J. 1975, iii, 346. 5. Littler, W. A., Honour, A. J., Pugsley, D. J., Sleight, P. Circulation, 1975, 51, 1101. 6. Littler, W. A., West, M. J., Honour, A. J., Sleight, P. Am. Heart J. 1978, 95, 180. 7. Littler, W. A., Honour, A. J., Sleight, P., Stott, F. D. Br. med. J. 1972, iii, 4.
justified. cases
CIRCADIAN VARIATION IN BLOOD-PRESSURE
76.
’
be
incriminated, since several reports indicate that dur-
ing propranolol therapy for thyrotoxicosis, thyroxine levels either increase slightly or remain unchanged. 10.11 Since thyroidal secretory activity may spontaneously resume and evolve into thyrotoxicosis after transient post-’3’I hypothyroidism, it is wise to allow an interval of observation before starting exogenous thyroid-hormone replacement in this un-
the peroxidase-counts the plasma-cells were also counted in sections stained by methyl-green/pyronin (first biopsy 643±226, second biopsy 260±57). The increase in all classes of Ig in the first biopsy specimen indicated a polyclonal, and therefore not neoplastic, response; the figures for the second biopsy were all normal. This case shows that giardiasis can produce severe atrophy of the jejunal mucosa with a dense plasma-cell infiltrate without underlying disease and with complete recovery after treaton
ment.
Departments of Pathology St. Mary’s Hospital, London W2
and
Gastro-enterology,
W. K. BLENKINSOPP J. A. GIBSON G. P. HAFFENDEN
usual context. Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Pennsylvania 17033, U.S.A.
ELISA FOR RHEUMATOID FACTOR
J.
D. VELDHUIS
GIARDIASIS AND SEVERE JEJUNAL ABNORMALITY
SIR,-Malabsorption occurs in some patients with Giardia lamblia infection of the small gut; it was found in 29 of 40 patients with symptoms due to giardiasis.’ In symptomatic cases the jejunal mucosa usually shows a mild or moderate abnormality of architecture.2 We have seen a patient in whom jejunal biopsy revealed a heavy infection with G. lamblia, severe partial villous atrophy, and a dense plasma-cell infiltrate of the lamina propria; the changes were sufficient to warrant biopsy after treatment to establish that there was no underlying disease. This 65-year-old woman had had watery diarrhoea 3 weeks after returning to England from a 2-week tour of the Far East. 14 weeks after her return she had lost some 3 kg in weight and had obvious pitting oedema of both ankles with a normal jugular venous pressure. Her haemoglobin, white-cell count, eosinophil-count, and st;rum-vitamin-BI2 were normal; her mean corpuscular volume was 100-103 fl; the bone-marrow showed no megaloblasts, but part 1 of the Schilling test gave an abnormal result (6.2% of loading dose excreted). Serum-albumin (26-36 g/1) was low, fsecal fat excretion was 34.7and 48.7mmol/24 h (normal less than 18), and a xylose-tolerance test gave an equivocal result. Six stool specimens examined for parasites were negative, and barium studies were normal. No parasites were found in the jejunal aspirate, but jejunal biopsy showed the changes described above. The patient was given a 7-day course of metronidazole (200 mg three times a day), whereupon her diarrhoea ceased, and over the subsequent 4 months her weight and laboratory findings returned to normal; jejunal biopsy 8 weeks after treatment showed a normal mucosa. Plasma cells were identified by the peroxidase-antiperoxidase method in 5 µm paraffin sections of the formalin-fixed tissue and counted in the lamina propria overlying a unit length of muscularis mucosx. Mean values (±s.D.)/mm muscularis mucosa were, at the first biopsy, IgA 466+140, IgM 94±43, IgG 180±114 (total 740); and at the repeat biopsy they were IgA 180±54, IgM 49+17, IgG 11+9 (total 240). As a check 5. Irvine, W. J., Gray, R. S., Morris, P. J., Ting, A. Lancet, 1977, i, 898. 6. Toft, A. D., Seth, J., Hunter, W. M., Irvine, W. J. ibid. 1974, i, 704. 7. Braverman, L. E., Woeber, R. A., Ingbar, S. H. New Engl. J. Med.
1969, 281, 816. 8. Utiger, R. D. ibid. 1972, 287, 562. 9. Braverman, L. E., Ingbar, S. H., Vagenakis, A. G. J. clin. Endocr. Metab. 1971, 32, 515. 10. Harrower, A. D. B., Fyffe, J. A., Horn, D. B., Strong, J. A. Clin. Endocr. 1977, 7, 41. 11. Lotti, G., Delitala, G., Devilla, L. ibid. 1977, 6, 405. 1. Wright, S. G., Tomkins, A. M., Ridley, D. S. Gut, 1977, 18, 343. 2. Thompson, A., Rowland, R., Hecker, R., Gibson, G. E., Reid, D. P. J. clin. Path. 1977, 30, 292.
SIR,-Early detection of rheumatoid factor may have prognostic value for patients with rheumatoid arthritis. Diagnostic tests such as latex fixation (Singer and Plotz) and sheepcell agglutination (Rose-Waaler) may exhibit some lack of specificity and sensitivity. The enzyme-linked immunosorbent assay (ELISA) may be a very sensitive test for detection of antigens and antibodies.’ We have used ELISA to investigate specificity, sensitivity, and reproducibility of this assay system for detection of rheumatoid factor. Flatbottom microtitre plates (Dynatech M129A) were coated with rabbit IgG (1 mg/dl) according to the method described by Voller et a1.2 Two-fold dilutions of serum were assayed with a solid-phase indirect technique with goat antihuman IgM peroxidase. The amount of fixed peroxidase was determined with 5-aminosalicylic acid and hydrogen peroxide as substrate. Sera from 132 patients submitted for rheumatoid-factor testing were investigated. 93 sera were latex-fixation positive and 39 were negative. All sera were further tested by Rose-Waaler microtitre assay with sheep erythrocytes sensitised with rabbit antisheep IgG and by ELISA. Preliminary studies proved that ELISA was 3 times more sensitive than the Rose-Waaler test. Sera with titres at or below 1/50 in ELISA were considered negative, compared with titres 1/16 in the Rose-Waaler test:
The coefficient of correlation was 84%. Only 5 out of the 18 latex-positive sera were scored as strong reactive. All 18 sera were negative in the Rose-Waaler test and in a quantitative latex-fixation assay (1/40). This finding may be caused by the fact that the latex-fixation test, although more sensitive, is less diagnostically specific. The 3 latex-fixation negative, ELISApositive sera were 1/100 reactive in ELISA, and 2 sera scored 1/32 and 1/64 in the Rose-Waaler test. A comparison between the diagnostically more specific RoseWaaler test and ELISA gave the following results: -
The coefficient of correlation of this test was 93%. Only 1 out of the 10 Rose-Waaler negative ELISA positives (titre 100-400) proved to be latex-fixation negative. The reproducibility and sensitivity of ELISA in repeated tests were better than those for the Rose-Waaler test. Furthermore spectrophotometric readings of the results can be made, and this is under investigation. The specificity of the ELISA test was further investigated. 40 sera from patients positive for streptolysin, brucella, sal1. Engvall, E., Perlmann, P. J. Immun. 1972, 109, 129. 2. Voller, A., and others Bull. Wld Hlth Org. 1976, 53, 55.
995
monella, or gonococcal antibodies or infectious mononucleosis proved to be negative in the ELISA test. ELISA can be used as a specific, sensitive, and reproducible assay of rheumatoid factor. However, further standardisation is necessary.
as
for
most ELISA
tests,
Department of Medical Microbiology, Institute Medical Laboratories and Ignatius Hospital, Breda, Netherlands
F. TH. C. WILLEMS C. C. M. KLAASSEN DE KORT
since they may have no further seizures. Case 3 is now classified correctly, but he was incorrectly classified at his school medical. Although only a very small sample, these cases raise a number of questions: are c.M.o.s properly trained to make these very important decisions; are equally inappropriate restrictions being applied to children with other chronic conditions ; and should not the medical records of all children be reviewed just before they leave school, because their state of health may have changed? I thank Dr R. Wilson and Dr M.
Roxby
for advice and encourage-
ment.
EPILEPSY AND THE SCHOOL LEAVER’S MEDICAL
SiR,--One of the duties of a clinical medical officer (c.M.o.) is the medical examination of pupils in their last year of comeducation. This is the last routine school medical examination the adolescent will have even though he or she may stay on for two years or more. The c.M.o. has to decide if the school leaver’s subsequent employment should be restricted in any way. Any restrictions are entered on a special form (Y9). Where a pupil has or has had a chronic illness the decision can be difficult. If restrictions are enforced the adolescent may find some forms of employment closed to him, so the decision is important. Problems often arise with epilepsy, and I decided to review the records of children labelled as epileptic in the borough in which I was working. Of 20 281 children in ordinary State schools, 49 were labelled as epileptic, and 7 of these had had school leavers’ medicals:
for Sick Children, London WC1N 3JH
Hospital
DAVID ELLIMAN
pulsory
Case 1.-Girl of 17. Nocturnal seizures between the ages of 12y and 13. Since her first seizure she had been on continuous anticonvulsants. School leavers’ medical at age 15. Case 2.-Boy of 16. One seizure at age 12 in association with rubella encephalitis. Since then he has been on anticonvulsants continuously. At the time of his school leavers’ medical (age 16y) he was being weaned off them. Case 3.-Boy of 16. Two seizures in association with encephalitis at age 9 years. He had been on continuous medication until, after slow reduction, this was stopped very recently. School leavers’ medical at age 15, before anticonvulsants were tapered off. Case 4.-Boy of 16. Seizures at age 8 and 12. Since the second seizure he has been on continuous medication and is seizure-free. School leavers’ medical at age 15. Case 5.-Girl of 16 who started having "funny turns" at age 7. She was put on anticonvulsants. At age 14 medication was stopped and it was decided the "turns" had been fainting episodes rather than seizures. At a school leavers’ medical when 16 years old, she had been free of "turns" and off medication for 2 years. Case 6.-Boy of 15 2. Started having seizures when aged 10 and is now fairly well-controlled on medication though he still has occasional seizures. School leavers’ medical at 15 2 Case 7.-Boy of 16 who had his only seizure at age lly. He had been on medication from then until it was discontinued at about age 15. He has had no further seizures and his school leavers’ medical was done at age 15(9 months after treatment stopped).
On the Y9s of all these pupils except case 7 the c.M.o. had stated: "In my opinion this pupil is not suitable for work at heights or near vehicles in action". Leaving aside the question of the original diagnosis and treatment, at the time of their medicals all but cases 2 and 7 would have been legally entitled to a full driver’s licence (assuming they were old enough and had no other disabilities). Logically therefore, any employment restrictions in cases 1, 3, 4, 5, and 6 might not seem justifiable. Case 2 would not be eligible for a licence so some restrictions might be iri order. Case 3 would not now be eligible for a drivers’ licence and so, while restrictions may not have been justifiable at the time of his medical, they would now. As case 7 had been off treatment for only 9 months before his medical, restrictions could well be
On the
StR,—The results described by Dr Millar Craig and his colp. 797) are not only of practical but also of theoretical interest. The enormous fall of arterial presgreat sure during sleep was a great surprise to us when we first observed it using the first fully automatic apparatus for recording arterial pressure in the absence of an observer.’ The size of the fall was amply confirmed when we used Dr Stott’s improved apparatus,2 also used by Millar Craig and others. (Why did they not refer to the earlier paper whose results they confirmed ?) The cardiovascular changes during sleep were analysed by my colleagues.3 They are usually attributed to the change in the activity of the reticular formation in the brain. Have Millar Craig and his colleagues plotted blood-pressure and pulse together on the same graph? If so, did the changes parallel one another? They should have, if they severally reflect the activity of the reticular formation.
leagues (April 15,
5 Horwood Close,
Headington, Oxford OX3 7RF
criterion of
eligibility for a drivers’ licence being unfairly restricted; case 7 should, perhaps have some restrictions imposed but has not; and cases 2, 3, and 6 are justifiably restricted. However, cases 2 and 7 should be reviewed 2 years after medication has been stopped simple
1, 4, and 5
were
GEORGE PICKERING
SiR,—We have demonstrated4-6 that the most important determinants of blood-pressure variability over a 24 h period are physical activity and sleep. We were therefore surprised that Dr Millar Craig and his colleagues did not seem to take physical activity into sufficient account in their analysis of changes in blood-pressure in the early morning. From their grouped data it is impossible to determine when their patients awoke; in our experience such patients often awaken early in the morning, and it is inconceivable that they would all awaken simultaneously. We found no significant rise in bloodpressure before awakening, but we did find that, after awakening, pressure rises but is further affected by physical activity. The figure represents group data on eighteen patients (average age 40, range 21-58) who had continuous intra-arterial blood pressure recorded over 24 h.7 Casual blood-pressure averaged 150/96 mm Hg (range 120/70 to 230/120) and all were untreated at the time of study. To clarify the influence of sleep and awakening we determined the time at which each patient woke and used that as our reference point. Blood-pressure was then averaged over 30 min periods backwards throughout 1.
D. W., Honour, A. J., Fenton, G. W., Stott, F. W., Pickering, G. W. Clin. Sci., 1964, 26, 445. 2. Bevan, A. T., Honour, A. J., Stott, F. H. ibid, 1969 36, 329. 3. Bristow, J. D., Honour, A. J., Pickering, T. G., Sleight, P. Cardiovasc. Res.
Richardson,
1969, 3, 476. Littler, W. A., Honour, A. J., Carter, R. D., Sleight, P. Br. med. J. 1975, iii, 346. 5. Littler, W. A., Honour, A. J., Pugsley, D. J., Sleight, P. Circulation, 1975, 51, 1101. 6. Littler, W. A., West, M. J., Honour, A. J., Sleight, P. Am. Heart J. 1978, 95, 180. 7. Littler, W. A., Honour, A. J., Sleight, P., Stott, F. D. Br. med. J. 1972, iii, 4.
justified. cases
CIRCADIAN VARIATION IN BLOOD-PRESSURE
76.
’
