152
worrying feature of the report was the increased demandof patients for analgesia as full dilatation approached, thus increasing the risk of depressing the infant. It is no reassurance that the apparatus was not used during the second stage of labour; the second stage should not last long enough to allow the fetus time to excrete much of the drug, nor is there any guarantee that second stage will be diagnosed at the correct time and the apparatus stopped. Dr Evans and his colleagues state that "it should be possible to dispense, in part, with the clinician’s presence". Does this mean that it is no longer necessary for the mother to have a midwife at hand during labour, and a doctor readily available? No one wants a woman in labour to suffer unnecessarily, but there are ways of comforting someone who is frightened and in pain other than by sticking a needle--or a cannula-into A
rate
her. Children’s Hospital, Durham Road,
Sunderland, Tyne and Wear.
R.
J. ROWLATT
STOOL CHARACTERISTICS AND WESTERN DISEASES
SIR,-Evidence is accumulating in support of a relationship between stool characteristics and the content of fibre in the diet on the one hand, and the prevalence of certain characteristically Western diseases on the other.’ Diseases whose prevalence rises within a few years of changes in diet, and consequently in stool characteristics, include appendicitis and at the other end of the scale are diverticular disease of the colon and hiatus hernia which require several decades on a new dietary regimen. The population of Malaysia is multiracial and contains a wide diversity of socioeconomic groups, with differing dietary habits. Intestinal transit-times, measured by Hinton’s method,2 and daily stool weights have been recorded in representative population groups. The 25 radio-opaque markers were swallowed in the evening; and, since many of the stools were collected from villagers not owning watches, only the day on which they were passed could be recorded. Times recorded by those with watches showed, however, that the almost invariable pattern was one stool daily passed early in the morning. The results are shown in the accompanying table. All the rural communities, which were the poorer ones, whose diet is predominantly little-processed vegetable foods, including rice with very little animal protein, had daily stool
haemorrhoids, whereas
1. 2.
Burkitt, D. P., Trowell, H. C., Refined Carbohydrate Foods and Disease. London, 1975. Hinton, J. M., Lennard Jones, J. E., Young, A. C. Gut, 1969, 10, 842.
weights averaging well above 300 g, which is up to or above levels recorded in African,3 Indian,and Peruvian5 villagers. Moreover, the weight of stool passed daily was much more conthan is usual in Western communities. The urban dwellers, including the doctors, now take much white bread, sugar, and processed foods in their diet, and eat much larger quantities of meat and less vegetables than do the villagers. They had stool weights approximating to, but still significantly in excess of, Western averages. The diet of doctors, representing the top socioeconomic group, approximates most closely to that of Western nations, and their breakfasts are composed almost entirely of white bread and low-fibre cereals. Sugar, white bread, and processed foods loom large in their menus, and meat consumption is
stant
high. They alone had
stool weights comparable to reported Western averages. It is significant that appendicitis is more prevalent in urban than in rural dwellers and that the prevalence of coronary heart-disease, obesity, and bowel cancer is increasing in the upper strata of the society. In no group are diverticular disease or hiatus hernia vet other than rare. Obtaining stool samples from village communities demands much determination and dogged persistence and we are particularly indebted to the surgical residents who undertook these collections. General Hospital, Kuala Lumpur,
Malaysia.
M. BALASEGARAM
Medical Research Council, External Scientific Staff, 172 Tottenham Court Road, London W1P 9LG.
D. P. BURKITT
PRENATAL DIETHYLSTILBŒSTROL EXPOSURE AND MALE HYPOGONADISM SiR,—The association between prenatal exposure to diethylstilboestrol and abnormalities of the lower genital tract in females has been well established.6 The possible effect of the hormone on male offspring has, to my knowledge, not been
documented. I have under my care a 17-year-old boy with the typical clinical and laboratory findings of hypogonadotropic hypogonadism with anosmia (Kallmann syndrome). His mother had taken large doses of diethylstilbrestrol throughout the pregnancy, because of earlier spontaneous miscarriages. Although I realise that the syndrome occurs as a familial 3. Burkitt, D. P., Walker, A. R. P., Painter, N. S. Lancet, 4. Tandon, R. K., Tandon, B. N. ibid. 1975, ii, 560. 5. Crofts, T. J. ibid. 1975, i, 801. 6. Herbst, A. L. New Engl. J. Med. 1975, 292, 334.
INTESTINAL TRANSIT-TIMES AND STOOL WEIGHTS IN DIFFERENT GROUPS IN MALAYSIA
.
*1 recorded 1st
I
I
day only, when
15
were
passed.
1972, ii, 1408.
153
disorder, it would be of interest to know if others have encountered this association. Department of Maternal and Child Health, Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire 03755, U.S.A.
the erythrocyte-sedimentation rate.
DICK HOEFNAGEL
CIRCULATING IMMUNE COMPLEXES IN
ERYTHEMA NODOSUM AND EARLY SARCOIDOSIS
SIR,-Sarcoidosis is associated with immunological abnormalities.’ Often immunoglobulin levels are significantly raised,’ and delayed-hypersensitivity reactions are depressed.33 Indirect evidence that immune complexes might be present in 4 serum is provided by the observation of Oreskes and Siltzbach that rheumatoid factor may be found, especially when the disal.,’ however, found no evidence of complement activation in chronic sarcoidosis, though levels of CH50, C4, and C2 were elevated in some patients. Deposits of immunoglobulin and complement have been found in or around the granulomatous lesions in lymph-nodes in patients with sarcoidosis6and in sarcoid lesions in lung-biopsy speease
is active. Sheffer
in all the cases we have studied the widespread disturbances in the complement system were exactly paralleled by changes in
et
cimens.’ Skin lesions of erythema nodosum leprosum contain granular deposits of immunoglobulin and complement,9 and patients with this disorder may have circulating immune complexes reactive with Clq.1O Hedfors and Norberg," using the plateletaggregation test to detect circulating immune complexes, reported positive results in 6 out of 26 patients with sarcoidosis, including 4 out of 5 with erythema nodosum and bilateral hilar lymphadenopathy.
We have studied 22 patients during an acu’.e episode of erythema nodosum. All patients were seen within 10 days of the onset of symptoms, and most were followed at intervals until symptoms subsided. All patients had a chest X-ray when first seen. 19 had evidence of bilateral hilar lymphadenopathy, and this group was considered to have sarcoidosis. 2 patients had a severe sore throat 7-10 days before developing erythema nodosum, and in 1 of these a profuse growth of p-haemolytic streptococci was cultured from a throat swab. In the other patient no precipitating cause was found. Serum was taken at the first visit and at intervals until symptoms subsided. The following tests were carried out in an attempt to detect changes due to circulating immune complexes: C3 and C4 levels, C3-activation products (C3i), anticomplementary activity, platelet aggregation, and Clq precipitation. Details of the methods and a full analysis of the results will be published in detail later."
18 out of 22 cases had disturbances of serum complement at the time of presentation. The commonest abnormality was C3i (in 14 of 18 patients tested). CH50 was reduced in 4 out of 18, and anticomplementary activity was found in 8 out of 16. Only 2 patients out of 13 showed a precipitation reaction with Clq, but 6 out of 10 were positive in the platelet-aggregation test. 13 patients were followed serially for 83 days from the onset of symptoms. In general, clinical improvement was accompanied by the return of the serological abnormalities to normal. Only 2 patients showed abnormality at 40 days. This study produced definitive evidence for the first time that free immune complexes appear in the serum during the early stages of acute sarcoidosis and gradually disappear as symptoms subside. It is important, however, to point out that 1. Siltzbach, L. E. Practitioner, 1969, 202, 613. 2. Buckley, E. C., III, Dorsey, F. C. Ann. intern. Med. 1970, 72, 37. 3. Jones, J. V. Clin. exp. Immun. 1967, 2, 477. 4 Oreskes, I., Siltzbach, L. E. Am. J. Med. 1968, 44, 60. 5 Sheffer, A. L., Ruddy, S., Israel, H. L., in 5th International Conference on Sarcoidosis: XIVth Scientific Conference of the Medical Faculty of Charles University (edited by L. Levinsky and F. Macholda); p. 195. Prague, 1971. 6. Mellors, R. C., Ortega, L. G., Noyes, W. F., Holman, H. R. Am. J. Path.
1957, 33, 613. 7 Wanstrup, J., Elling, P. Acta path. microbiol. scand. 1968, 73, 37. 8 Ghose, T., Landrigan, P., Asif, A. Chest, 1974, 66, 264. 9 Wemambu, S. N. C., Turk, J. L., Waters, M. F. R., Rees, R. J. W. Lancet, 1969, ii, 933. 10 Moran, C. J., Ryder, G., Turk, J. L., Waters, M. R. F. ibid. 1972, ii, 572. 11 Hedfors, E., Norberg, R. Clin. Exp. Immun. 1974, 16, 493. 12 Jones, J. V., Cumming, R. H., Asplin, C. M., Laszlo, G., White, R. J. Ann. N.Y.Acad. Sci. (in the press).
University Department of Medicine, University of Bristol,
J. VERRIER JONES R. H. GUMMING
Southmead Hospital, Bristol BS10 5NB. Southmead Hospital.
C. M. ASPLIN
Bristol Royal Infirmary.
G. LASZLO
Frenchay Hospital.
R. J. WH
EARLY BREAST CANCER AND POSTOPERATIVE IRRADIATION
SiR,—The recent debates on this subject provide no evidence that postoperative irradiation prolongs survival. Indeed, 16 years ago Patterson and Russell’ published carefully analysed data indicating reduced survival of women under 45 years without axillary-node metastases after radical mastectomy followed by irradiation of the operation site and its environs. Retrospective surveys23 seem to support this finding, but in view of the extensive and prolonged depletion of lymphocytic subpopulations after irradiation4 the reduction in survival of irradiated patients is surprisingly small. The failure to prolong overall survival indicates that postoperative irradiation should not be prescribed for every patient, but it does not provide grounds for discarding this method altogether. The survival of some patients with mammary cancer may be prolonged by irradiation, and they should be identified to allow rational prescription. Although Professor Levitt and Professor McHugh (Dec. 20, p. 1258) regard Stjernsward’s view5 that irradiation reduces overall survival as ill-founded, the debate will have little relevance to clinical practice until a survival advantage for irradiation is clearly demonstrated. This may evolve from combinations of irradiation with immunological6 or pharmacological radio-sensitisers. Meanwhile, the only other indication for postoperative irradiation is non-disseminated extensive regional nodal cancer thought to be unsuitable for systemic treatment by endocrine or chemical methods. Royal Infirmary, Glasgow G4 0SF.
J. MAXWELL ANDERSON
PROTECTION OF PERITONEAL-DIALYSIS CATHETER
SIR,— Peritoneal dialysis has become a widely accepted method of treatment for acute renal failure.7 A technical problem frequently encountered is discomfort from traction on the catheter and kinking where it protrudes from the abdominal wall. A simple method has been devised to overcome this problem and has been used successfully in both adults and children for several years. As this does not appear to be widely known it is briefly described here. The catheter is secured with a purse-string suture, and a waterproof dressing applied. A presterilised, disposable 100 ml polyethylene gallipot is inserted over the catheter which is threaded through a hole cut in its base as illustrated. The gallipot is then taped to the abdominal wall, the catheter trimmed to the required length, and the dialysis tubing attached by means of a right-angled connector. With this simple attach1. Patterson, R., Russell, M. H. J. Fac. Radiol. 1959, 10, 175. 2. Bond, W. H. in Treatment of Carcinoma of the Breast (edited by A. S. Jarrett); p. 24. Amsterdam, 1967. 3. Lipworth, L. Lancet, 1965, ii, 231. 4. Anderson, J. M., Campbell, J. B., Wood, S. E., Boyd, J. E., Kelly, F. Clin. Oncol. 1975, 1, 201. 5. Stjernswärd, J. Lancet, 1974, ii, 1285. 6. Anderson, J. M., Kelly, F., Wood, S. E., Halnan, K. E. Br. J. Surg. 1974, 61, 778. 7. Meadow, S. R., Cameron, J. S., Ogg, C. S. Lancet, 1970, ii, 797.
worrying feature of the report was the increased demandof patients for analgesia as full dilatation approached, thus increasing the risk of depressing the infant. It is no reassurance that the apparatus was not used during the second stage of labour; the second stage should not last long enough to allow the fetus time to excrete much of the drug, nor is there any guarantee that second stage will be diagnosed at the correct time and the apparatus stopped. Dr Evans and his colleagues state that "it should be possible to dispense, in part, with the clinician’s presence". Does this mean that it is no longer necessary for the mother to have a midwife at hand during labour, and a doctor readily available? No one wants a woman in labour to suffer unnecessarily, but there are ways of comforting someone who is frightened and in pain other than by sticking a needle--or a cannula-into A
rate
her. Children’s Hospital, Durham Road,
Sunderland, Tyne and Wear.
R.
J. ROWLATT
STOOL CHARACTERISTICS AND WESTERN DISEASES
SIR,-Evidence is accumulating in support of a relationship between stool characteristics and the content of fibre in the diet on the one hand, and the prevalence of certain characteristically Western diseases on the other.’ Diseases whose prevalence rises within a few years of changes in diet, and consequently in stool characteristics, include appendicitis and at the other end of the scale are diverticular disease of the colon and hiatus hernia which require several decades on a new dietary regimen. The population of Malaysia is multiracial and contains a wide diversity of socioeconomic groups, with differing dietary habits. Intestinal transit-times, measured by Hinton’s method,2 and daily stool weights have been recorded in representative population groups. The 25 radio-opaque markers were swallowed in the evening; and, since many of the stools were collected from villagers not owning watches, only the day on which they were passed could be recorded. Times recorded by those with watches showed, however, that the almost invariable pattern was one stool daily passed early in the morning. The results are shown in the accompanying table. All the rural communities, which were the poorer ones, whose diet is predominantly little-processed vegetable foods, including rice with very little animal protein, had daily stool
haemorrhoids, whereas
1. 2.
Burkitt, D. P., Trowell, H. C., Refined Carbohydrate Foods and Disease. London, 1975. Hinton, J. M., Lennard Jones, J. E., Young, A. C. Gut, 1969, 10, 842.
weights averaging well above 300 g, which is up to or above levels recorded in African,3 Indian,and Peruvian5 villagers. Moreover, the weight of stool passed daily was much more conthan is usual in Western communities. The urban dwellers, including the doctors, now take much white bread, sugar, and processed foods in their diet, and eat much larger quantities of meat and less vegetables than do the villagers. They had stool weights approximating to, but still significantly in excess of, Western averages. The diet of doctors, representing the top socioeconomic group, approximates most closely to that of Western nations, and their breakfasts are composed almost entirely of white bread and low-fibre cereals. Sugar, white bread, and processed foods loom large in their menus, and meat consumption is
stant
high. They alone had
stool weights comparable to reported Western averages. It is significant that appendicitis is more prevalent in urban than in rural dwellers and that the prevalence of coronary heart-disease, obesity, and bowel cancer is increasing in the upper strata of the society. In no group are diverticular disease or hiatus hernia vet other than rare. Obtaining stool samples from village communities demands much determination and dogged persistence and we are particularly indebted to the surgical residents who undertook these collections. General Hospital, Kuala Lumpur,
Malaysia.
M. BALASEGARAM
Medical Research Council, External Scientific Staff, 172 Tottenham Court Road, London W1P 9LG.
D. P. BURKITT
PRENATAL DIETHYLSTILBŒSTROL EXPOSURE AND MALE HYPOGONADISM SiR,—The association between prenatal exposure to diethylstilboestrol and abnormalities of the lower genital tract in females has been well established.6 The possible effect of the hormone on male offspring has, to my knowledge, not been
documented. I have under my care a 17-year-old boy with the typical clinical and laboratory findings of hypogonadotropic hypogonadism with anosmia (Kallmann syndrome). His mother had taken large doses of diethylstilbrestrol throughout the pregnancy, because of earlier spontaneous miscarriages. Although I realise that the syndrome occurs as a familial 3. Burkitt, D. P., Walker, A. R. P., Painter, N. S. Lancet, 4. Tandon, R. K., Tandon, B. N. ibid. 1975, ii, 560. 5. Crofts, T. J. ibid. 1975, i, 801. 6. Herbst, A. L. New Engl. J. Med. 1975, 292, 334.
INTESTINAL TRANSIT-TIMES AND STOOL WEIGHTS IN DIFFERENT GROUPS IN MALAYSIA
.
*1 recorded 1st
I
I
day only, when
15
were
passed.
1972, ii, 1408.
153
disorder, it would be of interest to know if others have encountered this association. Department of Maternal and Child Health, Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire 03755, U.S.A.
the erythrocyte-sedimentation rate.
DICK HOEFNAGEL
CIRCULATING IMMUNE COMPLEXES IN
ERYTHEMA NODOSUM AND EARLY SARCOIDOSIS
SIR,-Sarcoidosis is associated with immunological abnormalities.’ Often immunoglobulin levels are significantly raised,’ and delayed-hypersensitivity reactions are depressed.33 Indirect evidence that immune complexes might be present in 4 serum is provided by the observation of Oreskes and Siltzbach that rheumatoid factor may be found, especially when the disal.,’ however, found no evidence of complement activation in chronic sarcoidosis, though levels of CH50, C4, and C2 were elevated in some patients. Deposits of immunoglobulin and complement have been found in or around the granulomatous lesions in lymph-nodes in patients with sarcoidosis6and in sarcoid lesions in lung-biopsy speease
is active. Sheffer
in all the cases we have studied the widespread disturbances in the complement system were exactly paralleled by changes in
et
cimens.’ Skin lesions of erythema nodosum leprosum contain granular deposits of immunoglobulin and complement,9 and patients with this disorder may have circulating immune complexes reactive with Clq.1O Hedfors and Norberg," using the plateletaggregation test to detect circulating immune complexes, reported positive results in 6 out of 26 patients with sarcoidosis, including 4 out of 5 with erythema nodosum and bilateral hilar lymphadenopathy.
We have studied 22 patients during an acu’.e episode of erythema nodosum. All patients were seen within 10 days of the onset of symptoms, and most were followed at intervals until symptoms subsided. All patients had a chest X-ray when first seen. 19 had evidence of bilateral hilar lymphadenopathy, and this group was considered to have sarcoidosis. 2 patients had a severe sore throat 7-10 days before developing erythema nodosum, and in 1 of these a profuse growth of p-haemolytic streptococci was cultured from a throat swab. In the other patient no precipitating cause was found. Serum was taken at the first visit and at intervals until symptoms subsided. The following tests were carried out in an attempt to detect changes due to circulating immune complexes: C3 and C4 levels, C3-activation products (C3i), anticomplementary activity, platelet aggregation, and Clq precipitation. Details of the methods and a full analysis of the results will be published in detail later."
18 out of 22 cases had disturbances of serum complement at the time of presentation. The commonest abnormality was C3i (in 14 of 18 patients tested). CH50 was reduced in 4 out of 18, and anticomplementary activity was found in 8 out of 16. Only 2 patients out of 13 showed a precipitation reaction with Clq, but 6 out of 10 were positive in the platelet-aggregation test. 13 patients were followed serially for 83 days from the onset of symptoms. In general, clinical improvement was accompanied by the return of the serological abnormalities to normal. Only 2 patients showed abnormality at 40 days. This study produced definitive evidence for the first time that free immune complexes appear in the serum during the early stages of acute sarcoidosis and gradually disappear as symptoms subside. It is important, however, to point out that 1. Siltzbach, L. E. Practitioner, 1969, 202, 613. 2. Buckley, E. C., III, Dorsey, F. C. Ann. intern. Med. 1970, 72, 37. 3. Jones, J. V. Clin. exp. Immun. 1967, 2, 477. 4 Oreskes, I., Siltzbach, L. E. Am. J. Med. 1968, 44, 60. 5 Sheffer, A. L., Ruddy, S., Israel, H. L., in 5th International Conference on Sarcoidosis: XIVth Scientific Conference of the Medical Faculty of Charles University (edited by L. Levinsky and F. Macholda); p. 195. Prague, 1971. 6. Mellors, R. C., Ortega, L. G., Noyes, W. F., Holman, H. R. Am. J. Path.
1957, 33, 613. 7 Wanstrup, J., Elling, P. Acta path. microbiol. scand. 1968, 73, 37. 8 Ghose, T., Landrigan, P., Asif, A. Chest, 1974, 66, 264. 9 Wemambu, S. N. C., Turk, J. L., Waters, M. F. R., Rees, R. J. W. Lancet, 1969, ii, 933. 10 Moran, C. J., Ryder, G., Turk, J. L., Waters, M. R. F. ibid. 1972, ii, 572. 11 Hedfors, E., Norberg, R. Clin. Exp. Immun. 1974, 16, 493. 12 Jones, J. V., Cumming, R. H., Asplin, C. M., Laszlo, G., White, R. J. Ann. N.Y.Acad. Sci. (in the press).
University Department of Medicine, University of Bristol,
J. VERRIER JONES R. H. GUMMING
Southmead Hospital, Bristol BS10 5NB. Southmead Hospital.
C. M. ASPLIN
Bristol Royal Infirmary.
G. LASZLO
Frenchay Hospital.
R. J. WH
EARLY BREAST CANCER AND POSTOPERATIVE IRRADIATION
SiR,—The recent debates on this subject provide no evidence that postoperative irradiation prolongs survival. Indeed, 16 years ago Patterson and Russell’ published carefully analysed data indicating reduced survival of women under 45 years without axillary-node metastases after radical mastectomy followed by irradiation of the operation site and its environs. Retrospective surveys23 seem to support this finding, but in view of the extensive and prolonged depletion of lymphocytic subpopulations after irradiation4 the reduction in survival of irradiated patients is surprisingly small. The failure to prolong overall survival indicates that postoperative irradiation should not be prescribed for every patient, but it does not provide grounds for discarding this method altogether. The survival of some patients with mammary cancer may be prolonged by irradiation, and they should be identified to allow rational prescription. Although Professor Levitt and Professor McHugh (Dec. 20, p. 1258) regard Stjernsward’s view5 that irradiation reduces overall survival as ill-founded, the debate will have little relevance to clinical practice until a survival advantage for irradiation is clearly demonstrated. This may evolve from combinations of irradiation with immunological6 or pharmacological radio-sensitisers. Meanwhile, the only other indication for postoperative irradiation is non-disseminated extensive regional nodal cancer thought to be unsuitable for systemic treatment by endocrine or chemical methods. Royal Infirmary, Glasgow G4 0SF.
J. MAXWELL ANDERSON
PROTECTION OF PERITONEAL-DIALYSIS CATHETER
SIR,— Peritoneal dialysis has become a widely accepted method of treatment for acute renal failure.7 A technical problem frequently encountered is discomfort from traction on the catheter and kinking where it protrudes from the abdominal wall. A simple method has been devised to overcome this problem and has been used successfully in both adults and children for several years. As this does not appear to be widely known it is briefly described here. The catheter is secured with a purse-string suture, and a waterproof dressing applied. A presterilised, disposable 100 ml polyethylene gallipot is inserted over the catheter which is threaded through a hole cut in its base as illustrated. The gallipot is then taped to the abdominal wall, the catheter trimmed to the required length, and the dialysis tubing attached by means of a right-angled connector. With this simple attach1. Patterson, R., Russell, M. H. J. Fac. Radiol. 1959, 10, 175. 2. Bond, W. H. in Treatment of Carcinoma of the Breast (edited by A. S. Jarrett); p. 24. Amsterdam, 1967. 3. Lipworth, L. Lancet, 1965, ii, 231. 4. Anderson, J. M., Campbell, J. B., Wood, S. E., Boyd, J. E., Kelly, F. Clin. Oncol. 1975, 1, 201. 5. Stjernswärd, J. Lancet, 1974, ii, 1285. 6. Anderson, J. M., Kelly, F., Wood, S. E., Halnan, K. E. Br. J. Surg. 1974, 61, 778. 7. Meadow, S. R., Cameron, J. S., Ogg, C. S. Lancet, 1970, ii, 797.
