471 SODIUM EXCRETION AND SYMPATHETIC ACTIVITY IN RELATION TO SEVERITY OF HYPERTENSIVE DISEASE
SIR,-Berglund et al.’ report that when diagnosing essential hypotension their limits-175/115 mm Hg on two separate occasions two weeks apart, the measurements being done between 4.30 P.M. and 7.30 P.M.—corresponded to limits of 162/101 mm Hg when the measurements are taken on the same men at 8.00 A.M. The variation in blood-pressure with time of day reported in this paper is substantially greater than the 3-5 mm Hg reported in the National Health Survey publication.,
The mean change in systolic and diastolic blood pressure by time of home screen and time of the re-examination, shows that on re-examination blood-pressure fell in all four cells in table u for both systolic and diastolic pressures. The time-ofday effect is probably small relative to the regression effect. This would imply that the differences observed by Berglund et al. are largely due to regression toward the mean rather than variation in blood-pressure with time of day. H.D.F.P. Cooperative Study School of Public Health,
University of Texas, Houston, Texas 77025, U.S.A.
These findings are important both for patient care and for community-based studies of hypertension. To investigate this point further the average diastolic and systolic blood-pressures for subjects participating in the Hypertension Detection and Follow-up Program (H.D.F.P.) were computed for subjects
screened between 9.30-10.30
A.M.
and 4.30-5.30
P.M.
T.4BLE I-MEAN BLOOD-PRESSURE
IN
SUBJECTS
SCREENED
IN
THE
MORNING OR AFTERNOON
ROBERT J. HARDY GARY R. CUTTER C. MORTON HAWKINS
PITYRIASIS VERSICOLOR ALBA (SPECKLED TORSO SYNDROME) AND MEDITERRANEAN HOLIDAYS
Table
gives the mean blood-pressure, with the sample size in each category in parentheses. We have selected the morning and afternoon times which correspond as closely as possible to those reported by Berglund et al. I
Group,
SIR,-The attraction of Mediterranean beaches for North West European holidaymakers is largely responsible for the increased frequency with which pityriasis (tinea) versicolor alba is now being met with in the U.K. This is the name given to the clinical variant of pityriasis versicolor characterised by white macules at sites of infection instead of those with the more usual khaki or fawn colour. The lesions are usually symdistributed as they are nearly always more profuse the upper trunk and arms, the "speckled torso syndrome" would seem to be an appropriate name for the condition. Lesions however, may be restricted to quite small areas, such as one shoulder. No age is immune, the youngest patient seen so far is a 27-month-old girl whose speckling followed her first summer holiday in Portugal last year, but it is adolescents and young adults of both sexes who are more likely to be affected (e.g., the three members of a London football club who were worried about the speckling that followed their tour of Madagascar). This is not surprising because Pityrosporon orbiculare, the yeast-like microbe responsible for the infection, is virtually ubiquitous, and Roberts’ found that it was carried by over 90% of adolescents and adults studied in Cambridge. Sweating is the principal factor in precipitating infection as well as determining the extent to which the skin is involved. Ultraviolet light, especially that of sunshine, is lethal to the organism, and this is well demonstrated in those patients who display clinical and mycological evidence of infection on areas shielded from the sun by the brassière or bathing trunks while the exposed de-pigmented lesions are clinically, mycologically, and histologically free from infection. Ultrastructural studies from Paris, and those reported by A. L. Boiron from Bordeaux at the recent meeting of 1’Association des Dermatologistes et Syphiligraphes de Langue Française at Ajaccio, throw light on this apparent paradox. These show that there is a profound disturbance in the physiology of the melanocytes in the depigmented lesions, with striking reduction in, or total cessation of melanin production, associated with structural changes in the melanosine. These are small and round with a granular or lamellar matrix. The melanocytes lose contact with neighbouring cells (keratinocytes) ; indeed the only cells in contact with them are macrophages which have migrated from the dermis to occupy an electrolucent dilated space above the basilar membrane. Each macrophage is in close contact with an inactive melanocyte. This suggests not only that toxins from this microbe activate macrophages directly or indirectly, as in other infections, but also that some of these may have the property of inhibiting or disturbing melanin production when in contact with melanocytes. These changes may persist indefinitely in some individuals, although prompt repigmentation is the rule when the
metrically on
The variation in daily blood-pressures in the H.D.F.P. data does not reflect the same degree of variation with time of day that was reported by Berglund et al. but accords more closely with the National Health Survey publication. In part, the results reported by Berglund et al. on 19 persons with essential hypertension may be due to "regression toward the mean" since these subjects were selected by their screening procedure. The difference between the afternoon blood-pressures during screening and the morning blood-pressures during their re-examination is due to variation of blood-pressure with time of day and a regression effect due to the selection procedure used to screen the subjects in the afternoon. If the regression effect is large one would expect subjects screened in a similar way in the morning to show this same regression effect if re-examined in the afternoon. In the H.D.F.P. subjects were selected for a clinic visit if their diastolic blood-pressure in their home was greater than 95 mm Hg; hence, one would expect the regression effect to be larger in the diastolic than the systolic pressure. We have selected subjects who were screened in their home between 9.00 and 11.00 A.M. or between 3.00 and 5.00 P.M. The subjects subsequently had a visit to one of the H.D.F.P. clinics between 9.00 and 11.00 A.M. or between 3.00 and 5.00 P.M. table n). aiBLE II—CHANGES IN BLOOD-PRESSURE FROM HOME SCREEN TO CLINIC
RE-EXAMINATION
und, G., Wtkstrand, J., Wallentin, I., Wilhelmsen,
L.
Lancet, 1976, i,
324
nal Health Survey. Public Health Service Publications .:, no 13 Washington, D.C., 1964.
no.
1000, series
1. Roberts, S. O. B. Br. J. Derm. 1969, 81, 315. 2. Grupper, C., Cesarini, J. P., Pruinéras, M. Bull. Soc.
82, 114.
fr.
Derm.
Syph. 1975,
472 are exposed to sunlight during the following summer, short course of Methoxsalen and ammidin (‘Meladinine’) (two tablets daily taken 2 h before exposure to sunlight or ultraviolet light) will produce normal pigmentation after a few weeks in these patients. Treatment of active lesions by application of clotrimazole (’Canestan’) nightly after a bath for 12-14 days is usually effective, but the greater part of the skin surface, especially the lower limbs, where lesions may be very sparse, must be treated if prompt recurrence is to be avoided. Prophylactically, it would seem wise for those with speckled torsos to carry out this regimen once a week during subsequent visits to their holiday haunts. It would be interesting to see what the current cult of the sauna bath will bring in its train.
patches a
Guy’s Hospital, E.
London SE1 9RT
J. MOYNAHAN
URINARY ANTINUCLEAR FACTORS IN NEPHROTIC SYNDROME is well estaband some other diseases, but little is known about the test in urine except in
SIR The
lished in S.L.E.
L.E.
cell
test
in blood and
marrow
systemic lupus erythematosus (S.L.E.)
patients.
a simple technique, adding the urine of nephrotic patients to a suspension of donor leucocytes, we reproduced the characteristic cellular findings-i.e., L.E. cells, round hxmatoxylin bodies, and erythrocyte phagocytosis. We studied 11’ patients with various renal diseases with or without nephrotic syndrome and 20 healthy controls. Positive cellular tests were recorded (see table) only in patients with nephrotic syndrome regardless of the diagnosis. Urinary cellular tests were as a rule associated with an active glomerular process and an unfavour-
By
POSITIVE CELLULAR TESTS IN NEPHROTIC SYNDROME
VARICOSE VEINS IN DEVELOPING COUNTRIES
SIR,-Mr Hobbs (July 31, p. 259) is to be congratulated on his endeavours to confirm or refute suggestions that the prevalence of varicose veins might relate to bowel behaviour. Such studies are obviously of great value. My colleagues and I have found no constant relationship between frequency of defæcation and weight of stools passed. It would be of interest to know whether the long-standing constipation or diarrhoea which, in Mr Hobbs’ patients, bore no relationship to varicose-vein prevalence was measured in years or decades, since the age incidence of varicose veins suggests that very long exposure to some environmental factors is re-
sponsible. Mr Hobbs "cannot believe that the momentary daily excretory rise of intra-abdominal pressure can be the primary cause of varicose veins in the leg". The following facts must be considered. Abdominal straining does raise intra-abdominal pressures to a much greater extent than do other forms of exercise such as weight lifting.l These pressures which can exceed 200 mm Hg are readily transmitted to the veins of the lower limb when the valves become incompetent.2 They are sustained by the valves while these are competent3 and consequently must have some effect on them. Histological examination of incompetent veins shows widening of the circumference with consequent separation of the valve cusps usually without structural damage to the valves.4 The valves become incompetent sequentially from above downwards.’ In Singapore, trishaw riders who are constantly engaged in active exercise which entails contraction of abdominal muscles have a higher prevalence of varicose veins than do barbers who stand all day. The prevalence of varicose veins has been shown to relate directly to that of diverticular disease which is now widely accepted as resulting from constipating diets.’" These observations are consistent with the hypothesis that abdominal straining is one cause of varicose veins, but they do not prove the case. Where is the evidence that varicosities are related to "degenerative changes in the collagen of the subcutaneous tissue and skin"? I am not suggesting that raised intra-abdominal pressure is the
only
cause
of varicose veins, but it is the only cause sugamenable to preventive
gested that, if substantiated, would be action. Department of Morbid Anatomy, St Thomas’s Hospital Medical School, London SE1 7EH
DENIS P. BURKITT
1. Light, H. G., Routledge, J. A. Surgery, 1964, 56, 747. 2. Adams, J. C. Surg. Gynec. Obstet. 1939, 69, 717. 3. Martin, A., Odling-Smee, W. Lancet, 1976, i, 768. 4. Edwards, J. E., Edwards, E. A. Am. Heart. J. 1940, 19, 338. 5. Folse, R. Surgery, 1970, 68, 974. 6. Rajmohan, N. Singapore med. J. 1968, 9,167. 7. Latto, C., Wilkinson, R. W., Gilmore, O. J. A. Lancet, 1973, i, 1089. 8. Brodribb, A. J. M., Humphreys, D. M. Br. med. J. 1976, i, 424.
able prognosis. patients.
Blood
L.E.
cell
tests were
positive only in s.L,E,
The mechanism of urine-induced cellular tests is, we sug gest, connected with tissue destruction, phagocytosis at an inflammatory focus, and partial disintegration of phagocytes with release of degraded nuclear material, leading to secondary phagocytosis and a localised immune reaction similar to that seen in rheumatoid synovitis. Somehow, as happens in incomplete phagocytosis and raised deoxyribonuclease activity, free antibodies accumulate and are eliminated, together with che motaxic factors, in the urine.
Department of Internal Medicine, 1 Moscow Setchenow, Medical Institute, 119 021 Moscow, U.S.S.R.
E. M. TAREEV LYDIA W. KOZLOWSKAJA LUDMILA R. POLIANZEWA LUDMILA N. KOCHUBEJ
MALE SUSCEPTIBILITY TO PYRROLIZIDINE
ALKALOID POISONING
SIR In your Aug. 7 issue (p. 269) Dr Mohabbat and his colleagues describe an outbreak of hepatic veno-occlusive disease attributed to consumption of seeds of Heliotropiurr. plants. Remarkably, the disorder was almost twice as frequcc’. in males as in females. This unexpected distortion may have been due to some irrelevant influence, but my own interest the susceptibility of males derives from our studies’ which showed that under appropriate conditions male rats were more susceptible than females to monocrotaline, an alkaloid we known to produce lesions similar to those Dr Mohabbat an; his colleagues describe. Case Western Reserve University, Cleveland, Ohio 44106, U.S.A.
1.
OSCAR D. RATNOFF
Ratnoff, O. D., Mirick, G. S. Bull. Johns Hopkins Hosp. 1949, 84, 507
SIR,-Berglund et al.’ report that when diagnosing essential hypotension their limits-175/115 mm Hg on two separate occasions two weeks apart, the measurements being done between 4.30 P.M. and 7.30 P.M.—corresponded to limits of 162/101 mm Hg when the measurements are taken on the same men at 8.00 A.M. The variation in blood-pressure with time of day reported in this paper is substantially greater than the 3-5 mm Hg reported in the National Health Survey publication.,
The mean change in systolic and diastolic blood pressure by time of home screen and time of the re-examination, shows that on re-examination blood-pressure fell in all four cells in table u for both systolic and diastolic pressures. The time-ofday effect is probably small relative to the regression effect. This would imply that the differences observed by Berglund et al. are largely due to regression toward the mean rather than variation in blood-pressure with time of day. H.D.F.P. Cooperative Study School of Public Health,
University of Texas, Houston, Texas 77025, U.S.A.
These findings are important both for patient care and for community-based studies of hypertension. To investigate this point further the average diastolic and systolic blood-pressures for subjects participating in the Hypertension Detection and Follow-up Program (H.D.F.P.) were computed for subjects
screened between 9.30-10.30
A.M.
and 4.30-5.30
P.M.
T.4BLE I-MEAN BLOOD-PRESSURE
IN
SUBJECTS
SCREENED
IN
THE
MORNING OR AFTERNOON
ROBERT J. HARDY GARY R. CUTTER C. MORTON HAWKINS
PITYRIASIS VERSICOLOR ALBA (SPECKLED TORSO SYNDROME) AND MEDITERRANEAN HOLIDAYS
Table
gives the mean blood-pressure, with the sample size in each category in parentheses. We have selected the morning and afternoon times which correspond as closely as possible to those reported by Berglund et al. I
Group,
SIR,-The attraction of Mediterranean beaches for North West European holidaymakers is largely responsible for the increased frequency with which pityriasis (tinea) versicolor alba is now being met with in the U.K. This is the name given to the clinical variant of pityriasis versicolor characterised by white macules at sites of infection instead of those with the more usual khaki or fawn colour. The lesions are usually symdistributed as they are nearly always more profuse the upper trunk and arms, the "speckled torso syndrome" would seem to be an appropriate name for the condition. Lesions however, may be restricted to quite small areas, such as one shoulder. No age is immune, the youngest patient seen so far is a 27-month-old girl whose speckling followed her first summer holiday in Portugal last year, but it is adolescents and young adults of both sexes who are more likely to be affected (e.g., the three members of a London football club who were worried about the speckling that followed their tour of Madagascar). This is not surprising because Pityrosporon orbiculare, the yeast-like microbe responsible for the infection, is virtually ubiquitous, and Roberts’ found that it was carried by over 90% of adolescents and adults studied in Cambridge. Sweating is the principal factor in precipitating infection as well as determining the extent to which the skin is involved. Ultraviolet light, especially that of sunshine, is lethal to the organism, and this is well demonstrated in those patients who display clinical and mycological evidence of infection on areas shielded from the sun by the brassière or bathing trunks while the exposed de-pigmented lesions are clinically, mycologically, and histologically free from infection. Ultrastructural studies from Paris, and those reported by A. L. Boiron from Bordeaux at the recent meeting of 1’Association des Dermatologistes et Syphiligraphes de Langue Française at Ajaccio, throw light on this apparent paradox. These show that there is a profound disturbance in the physiology of the melanocytes in the depigmented lesions, with striking reduction in, or total cessation of melanin production, associated with structural changes in the melanosine. These are small and round with a granular or lamellar matrix. The melanocytes lose contact with neighbouring cells (keratinocytes) ; indeed the only cells in contact with them are macrophages which have migrated from the dermis to occupy an electrolucent dilated space above the basilar membrane. Each macrophage is in close contact with an inactive melanocyte. This suggests not only that toxins from this microbe activate macrophages directly or indirectly, as in other infections, but also that some of these may have the property of inhibiting or disturbing melanin production when in contact with melanocytes. These changes may persist indefinitely in some individuals, although prompt repigmentation is the rule when the
metrically on
The variation in daily blood-pressures in the H.D.F.P. data does not reflect the same degree of variation with time of day that was reported by Berglund et al. but accords more closely with the National Health Survey publication. In part, the results reported by Berglund et al. on 19 persons with essential hypertension may be due to "regression toward the mean" since these subjects were selected by their screening procedure. The difference between the afternoon blood-pressures during screening and the morning blood-pressures during their re-examination is due to variation of blood-pressure with time of day and a regression effect due to the selection procedure used to screen the subjects in the afternoon. If the regression effect is large one would expect subjects screened in a similar way in the morning to show this same regression effect if re-examined in the afternoon. In the H.D.F.P. subjects were selected for a clinic visit if their diastolic blood-pressure in their home was greater than 95 mm Hg; hence, one would expect the regression effect to be larger in the diastolic than the systolic pressure. We have selected subjects who were screened in their home between 9.00 and 11.00 A.M. or between 3.00 and 5.00 P.M. The subjects subsequently had a visit to one of the H.D.F.P. clinics between 9.00 and 11.00 A.M. or between 3.00 and 5.00 P.M. table n). aiBLE II—CHANGES IN BLOOD-PRESSURE FROM HOME SCREEN TO CLINIC
RE-EXAMINATION
und, G., Wtkstrand, J., Wallentin, I., Wilhelmsen,
L.
Lancet, 1976, i,
324
nal Health Survey. Public Health Service Publications .:, no 13 Washington, D.C., 1964.
no.
1000, series
1. Roberts, S. O. B. Br. J. Derm. 1969, 81, 315. 2. Grupper, C., Cesarini, J. P., Pruinéras, M. Bull. Soc.
82, 114.
fr.
Derm.
Syph. 1975,
472 are exposed to sunlight during the following summer, short course of Methoxsalen and ammidin (‘Meladinine’) (two tablets daily taken 2 h before exposure to sunlight or ultraviolet light) will produce normal pigmentation after a few weeks in these patients. Treatment of active lesions by application of clotrimazole (’Canestan’) nightly after a bath for 12-14 days is usually effective, but the greater part of the skin surface, especially the lower limbs, where lesions may be very sparse, must be treated if prompt recurrence is to be avoided. Prophylactically, it would seem wise for those with speckled torsos to carry out this regimen once a week during subsequent visits to their holiday haunts. It would be interesting to see what the current cult of the sauna bath will bring in its train.
patches a
Guy’s Hospital, E.
London SE1 9RT
J. MOYNAHAN
URINARY ANTINUCLEAR FACTORS IN NEPHROTIC SYNDROME is well estaband some other diseases, but little is known about the test in urine except in
SIR The
lished in S.L.E.
L.E.
cell
test
in blood and
marrow
systemic lupus erythematosus (S.L.E.)
patients.
a simple technique, adding the urine of nephrotic patients to a suspension of donor leucocytes, we reproduced the characteristic cellular findings-i.e., L.E. cells, round hxmatoxylin bodies, and erythrocyte phagocytosis. We studied 11’ patients with various renal diseases with or without nephrotic syndrome and 20 healthy controls. Positive cellular tests were recorded (see table) only in patients with nephrotic syndrome regardless of the diagnosis. Urinary cellular tests were as a rule associated with an active glomerular process and an unfavour-
By
POSITIVE CELLULAR TESTS IN NEPHROTIC SYNDROME
VARICOSE VEINS IN DEVELOPING COUNTRIES
SIR,-Mr Hobbs (July 31, p. 259) is to be congratulated on his endeavours to confirm or refute suggestions that the prevalence of varicose veins might relate to bowel behaviour. Such studies are obviously of great value. My colleagues and I have found no constant relationship between frequency of defæcation and weight of stools passed. It would be of interest to know whether the long-standing constipation or diarrhoea which, in Mr Hobbs’ patients, bore no relationship to varicose-vein prevalence was measured in years or decades, since the age incidence of varicose veins suggests that very long exposure to some environmental factors is re-
sponsible. Mr Hobbs "cannot believe that the momentary daily excretory rise of intra-abdominal pressure can be the primary cause of varicose veins in the leg". The following facts must be considered. Abdominal straining does raise intra-abdominal pressures to a much greater extent than do other forms of exercise such as weight lifting.l These pressures which can exceed 200 mm Hg are readily transmitted to the veins of the lower limb when the valves become incompetent.2 They are sustained by the valves while these are competent3 and consequently must have some effect on them. Histological examination of incompetent veins shows widening of the circumference with consequent separation of the valve cusps usually without structural damage to the valves.4 The valves become incompetent sequentially from above downwards.’ In Singapore, trishaw riders who are constantly engaged in active exercise which entails contraction of abdominal muscles have a higher prevalence of varicose veins than do barbers who stand all day. The prevalence of varicose veins has been shown to relate directly to that of diverticular disease which is now widely accepted as resulting from constipating diets.’" These observations are consistent with the hypothesis that abdominal straining is one cause of varicose veins, but they do not prove the case. Where is the evidence that varicosities are related to "degenerative changes in the collagen of the subcutaneous tissue and skin"? I am not suggesting that raised intra-abdominal pressure is the
only
cause
of varicose veins, but it is the only cause sugamenable to preventive
gested that, if substantiated, would be action. Department of Morbid Anatomy, St Thomas’s Hospital Medical School, London SE1 7EH
DENIS P. BURKITT
1. Light, H. G., Routledge, J. A. Surgery, 1964, 56, 747. 2. Adams, J. C. Surg. Gynec. Obstet. 1939, 69, 717. 3. Martin, A., Odling-Smee, W. Lancet, 1976, i, 768. 4. Edwards, J. E., Edwards, E. A. Am. Heart. J. 1940, 19, 338. 5. Folse, R. Surgery, 1970, 68, 974. 6. Rajmohan, N. Singapore med. J. 1968, 9,167. 7. Latto, C., Wilkinson, R. W., Gilmore, O. J. A. Lancet, 1973, i, 1089. 8. Brodribb, A. J. M., Humphreys, D. M. Br. med. J. 1976, i, 424.
able prognosis. patients.
Blood
L.E.
cell
tests were
positive only in s.L,E,
The mechanism of urine-induced cellular tests is, we sug gest, connected with tissue destruction, phagocytosis at an inflammatory focus, and partial disintegration of phagocytes with release of degraded nuclear material, leading to secondary phagocytosis and a localised immune reaction similar to that seen in rheumatoid synovitis. Somehow, as happens in incomplete phagocytosis and raised deoxyribonuclease activity, free antibodies accumulate and are eliminated, together with che motaxic factors, in the urine.
Department of Internal Medicine, 1 Moscow Setchenow, Medical Institute, 119 021 Moscow, U.S.S.R.
E. M. TAREEV LYDIA W. KOZLOWSKAJA LUDMILA R. POLIANZEWA LUDMILA N. KOCHUBEJ
MALE SUSCEPTIBILITY TO PYRROLIZIDINE
ALKALOID POISONING
SIR In your Aug. 7 issue (p. 269) Dr Mohabbat and his colleagues describe an outbreak of hepatic veno-occlusive disease attributed to consumption of seeds of Heliotropiurr. plants. Remarkably, the disorder was almost twice as frequcc’. in males as in females. This unexpected distortion may have been due to some irrelevant influence, but my own interest the susceptibility of males derives from our studies’ which showed that under appropriate conditions male rats were more susceptible than females to monocrotaline, an alkaloid we known to produce lesions similar to those Dr Mohabbat an; his colleagues describe. Case Western Reserve University, Cleveland, Ohio 44106, U.S.A.
1.
OSCAR D. RATNOFF
Ratnoff, O. D., Mirick, G. S. Bull. Johns Hopkins Hosp. 1949, 84, 507
