829 Observations remained nor24 h and 2 days later she was transferred to a psychiatric unit. Plasma-nomifensine concentrations were 2780 flg;1 on admission and 1915 g/1 the following morning. Peak levels of 20-50 g/1 were found after a single dose of 100 mg nomifensine.4 A comprehensive toxicological screen of plasma and urine from the patient detected no drugs apart from nomifensine. In this case the history was accurate, overdosage with nomifensine was confirmed analytically, and the ingestion of other drugs was excluded. In most of the cases of nomifensine poisoning reported to the manufacturers,s other drugs were taken and toxicological analyses were not done. We would be interested to hear from other clinicians who have encountered similar cases of nomifensine overdosage and we would be willing to make toxicological investigations. an
electrocardiogram was normal.
mal for the
next
S. MONTGOMERY P. CROME R. BRAITHWAITE
Department of Psychiatry and Poisons Unit, Guy’s Hospital, London SE 1
RHEUMATOID ARTHRITIS AND ORAL CONTRACEPTION
SiR,-In its report of a reduced incidence of rheumatoid arthritis associated with oral contraceptives (March 18, p. 569) the R.C.G.P. Oral Contraception Study does not give the method of statistical analysis, an important omission especially since the difference between numbers of first cases of rheumatoid arthritis seems small (37 in oral contraceptive takers/extakers and 57 in controls). Did the diagnoses of rheumatoid arthritis fit the definite or classical pattern as laid down by the American Rheumatism Association? This is a critical question. If the diagnosis is correct then we have annual incidence figures of the order of 0-3 5 per 1000. This is much lower than the population studies, which suggest an incidence of 2-6%. I have always felt that the figures for the incidence of rheumatoid arthritis given in the textbooks are too high, and the R.C.G.P. study would confirm this view. Department of Rheumatology and Rehabilitation, King’s College Hospital, London SE5 9RS
***This letter has been shown
to
Dr
HEDLEY BERRY
Kay, whose reply fol-
lows.-ED. L
SiR,—The statistical test was fully described by Mr Richard Peto in appendix III in our interim report.’ It is not practical to summarise this test here but we will send a photocopy to anyone who finds it inconvenient to refer to the original. In the context of a general morbidity study, we were unable to obtain sufficient detail about the specific criteria used for the diagnosis of rheumatoid arthritis to the extent recommended by international agreement. Our aim, therefore, was to determine that similar criteria were used in each of our contraceptive categories, and that comparisons between these groups were valid. This was the purpose of our special inquiry. We would not claim, however, that the diagnostic criteria were sufficiently strict for comparisons to be made with other populations, especially if they had different characteristics. Nevertheless, Wood2 has estimated an annual incidence of at least 0.2 per 1000 for both sexes, so that our estimate of approximately 0.5 per 1000, based on a population of women of reproductive age, is of a similar order of magnitude. We suspect that 4. Chamberlain, J., Hill, H. M. ibid. p. 117. 5. Hoechst Pharmaceuticals. Unpublished. 1. Royal College of General Practitioners. Oral
the figure Dr Berry quotes rather than incidence.
Oral Contraception Study, R.C.G.P. Manchester Research Unit, 8 Barlow Moor Road, Manchester M20 0TR
Contraceptives
London,1974. 2. Wood, P. H. M. in Copeman’s Text Book of the Rheumatic Diseases by J. T. Scott); chap. 3. Edinburgh, 1978.
(edited
’
CLIFFORD R. KAY SALLY J. WINGRAVE
PROSTAGLANDINS AND ACTINIC CANCER
SIR,-Professor Greaves (Jan. 28, p. 189) has proposed that prostaglandin E (P.G. E), by reducing proliferative activity in the epidermis, may protect the skin against the mutagenic effects of ultraviolet irradiation. If this is so we should expect find an increased incidence of solar keratosis in patients with psoriasis, since such patients have an increase in the rate of epidermal proliferation, and they have decreased P.G.E levels both in affected and unaffected skin.l,2 An Australian study has shown that psoriasis is associated, not with an increase, but with a considerable decrease in the incidence of solar keratosis.3 Of 819 men over the age of 45 without psoriasis 88% had solar keratosis, whereas of 51 men of the same age with psoriasis only 2 had solar keratosis. Whether this decreased risk of actinic malignancy in psoriasis is due to enhanced immunosurveillance as a result of the low P.G.E levels4 or to some other mechanism needs to be tested. to
Department of Dermatology,
Royal Infirmary, Bristol BS2 8HW
E. M. SAIHAN
J. L. BURTON
METHOD OF TOTAL VEIN INJECTION FOR VARICOSE VEINS
SIR,-Many of the large number of methods for the injection treatment of varicose veins demand multiple injections with prolonged bandaging to obtain satisfactory results. The method described here aims at injection of the whole varicosity, the vein being injected in the empty state, and when combined with careful bandaging, ensures in many cases a most satisfactory result. The patient lies with the affected limb raised at about 30° The leg is supported. A sphygmomanometer is placed round the upper thigh. The pressure in the manometer is raised to 50 mm Hg and the patient is instructed to move the foot up and down. The veins in the whole leg slowly distend and varicosities become easily recognisable. A satisfactory distension is achieved in three minutes. Using a radiopaque ’Teflon’ ’E-Z’ catheter (size 16 or possibly a little larger) with a needle length of 0.55 in a venepuncture is made in the prominent lower vein just above the ankle. When blood appears in the catheter the manometer is released; in about two minutes the raised limb has emptied the superficial veins. The leg may be stroked upwards to aid vein collapse. The needle assembly is then removed completely from the catheter, which is passed up the collapsed vein. There is often some difficulty in negotiating communicators but with some patience the catheter can be easily inserted up the vein to the region of the knee. It is possible to pass the catheter above this level but injection is best restricted to veins below knee level. The injection syringe is now connected to the catheter and as the catheter is slowly withdrawn the injection is made into the vein. A support tubegrip can be placed above the knee as the manometer is placed in position and this tubegrip can be unwound down the leg as the injection proceeds. The whole limb should then be carefully supported with sorKassis, V., Weismann, K., Heiligstadt, H. Sondergaard, J. Arch. derm. Res. 1977, 259, 207. 2. Aso, K., Denau, G., Krulig, L., Wilkinson, D. I., Farber, E. M. J. invest. Derm. 1975, 64, 326. 3. Kocsard, E. Aust. J. Derm., 1976, 17, 65. 4. Smith, E. B., Mason, W. V., Goodwin, J. S. Lancet, 1978, i, 561. 1.
and Health.
(2-6%) is an estimate of prevalence
830 borubber
pads over vein prominences. Crepe may be used but will require repeated readjustment to maintain reasonable pressure which should be maintained for 4-6 weeks. ’Elastoplast’ over the tubegrip is probably more practical since more satisfactory pressure can be maintained without readadjustment. If a vein injected while collapsed can be maintained in this state, the walls will adhere, and complete disappearance of the varicose condition may result from one injection. Occasional difficulty may be met in passing the catheter up the collapsed vein. Should this happen thevein can be redistended with the manometer, and this will usually allow satisfactory passage. When starting to practise this technique, the catheter can be passed up the distended vein but with experience the collapsed vein can be used in almost all cases. With support the patient is ambulant immediately after the injection and attends weekly for six weeks for inspection of the support bandaging. Three months should elapse before a second leg is injected. High venous ligation may with advantage, be combined in certain cases. Department of Surgery, Liverpool Royal Infirmary, Liverpool L3 5PU
A. C. BREWER
SEASONALITY IN SCHIZOPHRENIA
SiR,—Your editorial of March 4 suggested various mechanisms by which summer conception or spring birth might convey increased risk of schizophrenia across an interval of 20-30 years. Subsequent correspondents have made other suggestions. May I add mine. There is evidence of circadian abnormalities in schizophrenia. There is phase- shifting of the sleep rhythm and of the body-temperature rhythm,2and the body clock is fast. 3,4 Abnormal setting of body clock speed in infancy may be the factor linking spring birth with schizophrenia. In the northern hemisphere day-length increases throughout the first half of the year. A child born in January-April will therefore be exposed to increasing day-length for the first 2-6 months of its independent life. This early exposure for at least 2 months may be an important environmental factor interacting with hereditary factors to determine within limits the abnormally fast setting of the body clock. Plants and. lower animals monitor day length and have aspects of their "behaviour" controlled by it. The effect of spring days on day-active lower animals is to speed up their body clock which serves to prepare them for progressively earlier dawns. An effect which occurs transiently in mature lower animals may perhaps occur more permanently in the newborn human infant. The necessary monitoring apparatus could be located in the pineal. The excess of spring births occurs not only in schizophrenia but also in manic-depressive psychosis. Circadian abnormalities occur in both conditions too. Body-clock speed is known to vary quite widely between individuals (Bunning6 gives a range of 24.7-26.0h in health, while Wever7 cites a mean of 25 h±s.D. 0.56), but I know of no work on the variables associated with or determining different speeds. This explanation is compatible with Torrey’s finding that in the U.S.A. seasonal amplitude of schizophrenic births is less in the South than in the higher latitudes of New England or the Morgan, R., Drew, C. D. A. Soc Psychiat. 1970, 5, 99. Morgan, R., Cheadle, J. Br J. Psychiat. 1976, 129, 350. Morgan, R. ibid. 1977, 131, 504. Mills, J. N., Morgan, R., Minors, D. S., Waterhouse, J. M. Chronobiologia (in the press). 5. Cloudsley-Thompson, J. L. in The Voices of Time (edited by J. T. Fraser). London, 1968. 6. Bunning, E. The Physiological Clock. London, 1973. 7. Wever, R. Int. J. Chronobiol. 1975, 3, 19. 8. Torrey, E. F., Torrey, B. B., Petersen, M. R. Archs gen. Psychiat. 1977, 34,
1. 2. 3. 4.
1065.
Mid-West. It does
not
fit with the finding of seasonality in the varies little throughout the
Philippines9 (where day-length year). St Wulstans
Hospital,
ROGER MORGAN
Malvern, Worcs WR14 4JS
FOOD OR FREEDOM?
SIR,-Ihave read Food First by F. M. Lappé and J. Collins, whose book you discussed in an editorial.’ Their conclusions are depressing and sobering; they say the maldistribution of food is a political and economic problem, not a biological or technical one. They are most impressed with the manner in which the Chinese seem to have resolved certain aspects of agricultural production and distribution. A disturbing thought is prompted by this admiration of China. Would Lappe and Collins wish to submerge their own individual desires and aspirations, as is necessary under the Chinese system so that agricultural reform could follow? Also it seems that Cambodia is attempting to rearrange the priorities of its population, changing from "colonial" type cash crops to primary food production. The terrible price being paid by the Cambodian population for agrarian reform is frequently portrayed in news articles. Discussion of such a significant subject is most relevant to the readers of The Lancet. We doctors are often accused of being indifferent to, and ignorant of, nutrition. Institute for Health Care Studies of the United Hospital Fund of New York, New York, N.Y. 10222, U.S.A.
JUDITH M.
TAYLOR
DIAGNOSTIC PERITONEAL LAVAGE
SIR,-I write to comment
on your editorial about diagnostic in blunt abdominal trauma (March 11, p.
peritoneal lavage 541). Blood in the peritoneal cavity is not an absolute indication for exploration-indeed often it may be better not to know about it. A peritoneal lavage producing blood does not necessarily mean that a lesion requiring surgery is present-nor even that there is free interperitoneal blood. In one of my cases frank blood was produced after insertion of the cannula; at urgent laparotomy this bleeding proved to be due to cannulation of
a
vein in the small-bowel mesentery. There
was no
in-
terperitoneal lesion. The patient had a mildly contused left kidney which had been diagnosed preoperatively. I have been involved in four other cases where either no lesion was found or where there was some self-limiting process such as a minor liver tear not requiring treatment. In another case abdominal physical examination was made nearly useless because the lavaging fluid went into the rectus abdominus sheath. This patient was managed without laparotomy and recovered. The five cases I describe above had equivocal physical signs, and without lavage might not have been taken to the operating-room. I would accept criticism for these decisions, but it is a brave surgeon who decides against exploration when faced with a positive peritoneal lavage. My current practice in teaching is that when a resident feels that a peritoneal lavage is needed, then the investigation of choice is a consultant opinion. In North American hospitals all the preliminary investigations are usually done by residents of varying experience before the surgeon arrives on the scene. The consultant may thus be faced with a bloody tap before he has had the opportunity to make his own examination, a situation understandably pre-empting any clinical decision he might make. 9. Parker, G., Balza, B. Acta psychiat. 1. Lancet, 1977, ii, 1334.
scand. 1977, 56, 143.
electrocardiogram was normal.
mal for the
next
S. MONTGOMERY P. CROME R. BRAITHWAITE
Department of Psychiatry and Poisons Unit, Guy’s Hospital, London SE 1
RHEUMATOID ARTHRITIS AND ORAL CONTRACEPTION
SiR,-In its report of a reduced incidence of rheumatoid arthritis associated with oral contraceptives (March 18, p. 569) the R.C.G.P. Oral Contraception Study does not give the method of statistical analysis, an important omission especially since the difference between numbers of first cases of rheumatoid arthritis seems small (37 in oral contraceptive takers/extakers and 57 in controls). Did the diagnoses of rheumatoid arthritis fit the definite or classical pattern as laid down by the American Rheumatism Association? This is a critical question. If the diagnosis is correct then we have annual incidence figures of the order of 0-3 5 per 1000. This is much lower than the population studies, which suggest an incidence of 2-6%. I have always felt that the figures for the incidence of rheumatoid arthritis given in the textbooks are too high, and the R.C.G.P. study would confirm this view. Department of Rheumatology and Rehabilitation, King’s College Hospital, London SE5 9RS
***This letter has been shown
to
Dr
HEDLEY BERRY
Kay, whose reply fol-
lows.-ED. L
SiR,—The statistical test was fully described by Mr Richard Peto in appendix III in our interim report.’ It is not practical to summarise this test here but we will send a photocopy to anyone who finds it inconvenient to refer to the original. In the context of a general morbidity study, we were unable to obtain sufficient detail about the specific criteria used for the diagnosis of rheumatoid arthritis to the extent recommended by international agreement. Our aim, therefore, was to determine that similar criteria were used in each of our contraceptive categories, and that comparisons between these groups were valid. This was the purpose of our special inquiry. We would not claim, however, that the diagnostic criteria were sufficiently strict for comparisons to be made with other populations, especially if they had different characteristics. Nevertheless, Wood2 has estimated an annual incidence of at least 0.2 per 1000 for both sexes, so that our estimate of approximately 0.5 per 1000, based on a population of women of reproductive age, is of a similar order of magnitude. We suspect that 4. Chamberlain, J., Hill, H. M. ibid. p. 117. 5. Hoechst Pharmaceuticals. Unpublished. 1. Royal College of General Practitioners. Oral
the figure Dr Berry quotes rather than incidence.
Oral Contraception Study, R.C.G.P. Manchester Research Unit, 8 Barlow Moor Road, Manchester M20 0TR
Contraceptives
London,1974. 2. Wood, P. H. M. in Copeman’s Text Book of the Rheumatic Diseases by J. T. Scott); chap. 3. Edinburgh, 1978.
(edited
’
CLIFFORD R. KAY SALLY J. WINGRAVE
PROSTAGLANDINS AND ACTINIC CANCER
SIR,-Professor Greaves (Jan. 28, p. 189) has proposed that prostaglandin E (P.G. E), by reducing proliferative activity in the epidermis, may protect the skin against the mutagenic effects of ultraviolet irradiation. If this is so we should expect find an increased incidence of solar keratosis in patients with psoriasis, since such patients have an increase in the rate of epidermal proliferation, and they have decreased P.G.E levels both in affected and unaffected skin.l,2 An Australian study has shown that psoriasis is associated, not with an increase, but with a considerable decrease in the incidence of solar keratosis.3 Of 819 men over the age of 45 without psoriasis 88% had solar keratosis, whereas of 51 men of the same age with psoriasis only 2 had solar keratosis. Whether this decreased risk of actinic malignancy in psoriasis is due to enhanced immunosurveillance as a result of the low P.G.E levels4 or to some other mechanism needs to be tested. to
Department of Dermatology,
Royal Infirmary, Bristol BS2 8HW
E. M. SAIHAN
J. L. BURTON
METHOD OF TOTAL VEIN INJECTION FOR VARICOSE VEINS
SIR,-Many of the large number of methods for the injection treatment of varicose veins demand multiple injections with prolonged bandaging to obtain satisfactory results. The method described here aims at injection of the whole varicosity, the vein being injected in the empty state, and when combined with careful bandaging, ensures in many cases a most satisfactory result. The patient lies with the affected limb raised at about 30° The leg is supported. A sphygmomanometer is placed round the upper thigh. The pressure in the manometer is raised to 50 mm Hg and the patient is instructed to move the foot up and down. The veins in the whole leg slowly distend and varicosities become easily recognisable. A satisfactory distension is achieved in three minutes. Using a radiopaque ’Teflon’ ’E-Z’ catheter (size 16 or possibly a little larger) with a needle length of 0.55 in a venepuncture is made in the prominent lower vein just above the ankle. When blood appears in the catheter the manometer is released; in about two minutes the raised limb has emptied the superficial veins. The leg may be stroked upwards to aid vein collapse. The needle assembly is then removed completely from the catheter, which is passed up the collapsed vein. There is often some difficulty in negotiating communicators but with some patience the catheter can be easily inserted up the vein to the region of the knee. It is possible to pass the catheter above this level but injection is best restricted to veins below knee level. The injection syringe is now connected to the catheter and as the catheter is slowly withdrawn the injection is made into the vein. A support tubegrip can be placed above the knee as the manometer is placed in position and this tubegrip can be unwound down the leg as the injection proceeds. The whole limb should then be carefully supported with sorKassis, V., Weismann, K., Heiligstadt, H. Sondergaard, J. Arch. derm. Res. 1977, 259, 207. 2. Aso, K., Denau, G., Krulig, L., Wilkinson, D. I., Farber, E. M. J. invest. Derm. 1975, 64, 326. 3. Kocsard, E. Aust. J. Derm., 1976, 17, 65. 4. Smith, E. B., Mason, W. V., Goodwin, J. S. Lancet, 1978, i, 561. 1.
and Health.
(2-6%) is an estimate of prevalence
830 borubber
pads over vein prominences. Crepe may be used but will require repeated readjustment to maintain reasonable pressure which should be maintained for 4-6 weeks. ’Elastoplast’ over the tubegrip is probably more practical since more satisfactory pressure can be maintained without readadjustment. If a vein injected while collapsed can be maintained in this state, the walls will adhere, and complete disappearance of the varicose condition may result from one injection. Occasional difficulty may be met in passing the catheter up the collapsed vein. Should this happen thevein can be redistended with the manometer, and this will usually allow satisfactory passage. When starting to practise this technique, the catheter can be passed up the distended vein but with experience the collapsed vein can be used in almost all cases. With support the patient is ambulant immediately after the injection and attends weekly for six weeks for inspection of the support bandaging. Three months should elapse before a second leg is injected. High venous ligation may with advantage, be combined in certain cases. Department of Surgery, Liverpool Royal Infirmary, Liverpool L3 5PU
A. C. BREWER
SEASONALITY IN SCHIZOPHRENIA
SiR,—Your editorial of March 4 suggested various mechanisms by which summer conception or spring birth might convey increased risk of schizophrenia across an interval of 20-30 years. Subsequent correspondents have made other suggestions. May I add mine. There is evidence of circadian abnormalities in schizophrenia. There is phase- shifting of the sleep rhythm and of the body-temperature rhythm,2and the body clock is fast. 3,4 Abnormal setting of body clock speed in infancy may be the factor linking spring birth with schizophrenia. In the northern hemisphere day-length increases throughout the first half of the year. A child born in January-April will therefore be exposed to increasing day-length for the first 2-6 months of its independent life. This early exposure for at least 2 months may be an important environmental factor interacting with hereditary factors to determine within limits the abnormally fast setting of the body clock. Plants and. lower animals monitor day length and have aspects of their "behaviour" controlled by it. The effect of spring days on day-active lower animals is to speed up their body clock which serves to prepare them for progressively earlier dawns. An effect which occurs transiently in mature lower animals may perhaps occur more permanently in the newborn human infant. The necessary monitoring apparatus could be located in the pineal. The excess of spring births occurs not only in schizophrenia but also in manic-depressive psychosis. Circadian abnormalities occur in both conditions too. Body-clock speed is known to vary quite widely between individuals (Bunning6 gives a range of 24.7-26.0h in health, while Wever7 cites a mean of 25 h±s.D. 0.56), but I know of no work on the variables associated with or determining different speeds. This explanation is compatible with Torrey’s finding that in the U.S.A. seasonal amplitude of schizophrenic births is less in the South than in the higher latitudes of New England or the Morgan, R., Drew, C. D. A. Soc Psychiat. 1970, 5, 99. Morgan, R., Cheadle, J. Br J. Psychiat. 1976, 129, 350. Morgan, R. ibid. 1977, 131, 504. Mills, J. N., Morgan, R., Minors, D. S., Waterhouse, J. M. Chronobiologia (in the press). 5. Cloudsley-Thompson, J. L. in The Voices of Time (edited by J. T. Fraser). London, 1968. 6. Bunning, E. The Physiological Clock. London, 1973. 7. Wever, R. Int. J. Chronobiol. 1975, 3, 19. 8. Torrey, E. F., Torrey, B. B., Petersen, M. R. Archs gen. Psychiat. 1977, 34,
1. 2. 3. 4.
1065.
Mid-West. It does
not
fit with the finding of seasonality in the varies little throughout the
Philippines9 (where day-length year). St Wulstans
Hospital,
ROGER MORGAN
Malvern, Worcs WR14 4JS
FOOD OR FREEDOM?
SIR,-Ihave read Food First by F. M. Lappé and J. Collins, whose book you discussed in an editorial.’ Their conclusions are depressing and sobering; they say the maldistribution of food is a political and economic problem, not a biological or technical one. They are most impressed with the manner in which the Chinese seem to have resolved certain aspects of agricultural production and distribution. A disturbing thought is prompted by this admiration of China. Would Lappe and Collins wish to submerge their own individual desires and aspirations, as is necessary under the Chinese system so that agricultural reform could follow? Also it seems that Cambodia is attempting to rearrange the priorities of its population, changing from "colonial" type cash crops to primary food production. The terrible price being paid by the Cambodian population for agrarian reform is frequently portrayed in news articles. Discussion of such a significant subject is most relevant to the readers of The Lancet. We doctors are often accused of being indifferent to, and ignorant of, nutrition. Institute for Health Care Studies of the United Hospital Fund of New York, New York, N.Y. 10222, U.S.A.
JUDITH M.
TAYLOR
DIAGNOSTIC PERITONEAL LAVAGE
SIR,-I write to comment
on your editorial about diagnostic in blunt abdominal trauma (March 11, p.
peritoneal lavage 541). Blood in the peritoneal cavity is not an absolute indication for exploration-indeed often it may be better not to know about it. A peritoneal lavage producing blood does not necessarily mean that a lesion requiring surgery is present-nor even that there is free interperitoneal blood. In one of my cases frank blood was produced after insertion of the cannula; at urgent laparotomy this bleeding proved to be due to cannulation of
a
vein in the small-bowel mesentery. There
was no
in-
terperitoneal lesion. The patient had a mildly contused left kidney which had been diagnosed preoperatively. I have been involved in four other cases where either no lesion was found or where there was some self-limiting process such as a minor liver tear not requiring treatment. In another case abdominal physical examination was made nearly useless because the lavaging fluid went into the rectus abdominus sheath. This patient was managed without laparotomy and recovered. The five cases I describe above had equivocal physical signs, and without lavage might not have been taken to the operating-room. I would accept criticism for these decisions, but it is a brave surgeon who decides against exploration when faced with a positive peritoneal lavage. My current practice in teaching is that when a resident feels that a peritoneal lavage is needed, then the investigation of choice is a consultant opinion. In North American hospitals all the preliminary investigations are usually done by residents of varying experience before the surgeon arrives on the scene. The consultant may thus be faced with a bloody tap before he has had the opportunity to make his own examination, a situation understandably pre-empting any clinical decision he might make. 9. Parker, G., Balza, B. Acta psychiat. 1. Lancet, 1977, ii, 1334.
scand. 1977, 56, 143.
