260 valuable in countries where laboratory services are limited. Two patients seen in Ethiopia illustrate this point. A 56-year-old Ethiopian woman was admitted to hospital with a history of right hypochondrial pain, anorexia, and weight loss for 5 months and a left-sided neck swelling for 2 months. She was cachetic with a hard round mass in the anterior triangle of the neck on the left side measuring 5 cm in diameter. The liver was 11 cm below the right costal margin, hard, and grossly nodular. The only bruit heard was loud and restricted to the chest at the right midaxillay line, seventh to eighth intercostal space. No heart murmurs were heard and chest X-ray was normal. Biopsy of the neck mass revealed carcinoma, probably from liver, and a liver biopsy confirmed
hepatoma. A 48-year-old Ethiopian man was admitted with a history of weight loss and anorexia for a month, and abdominal swelling for 10 weeks. He had slight icterus and the liver was 8 cm below the right costal margin, slightly tender, hard, and nodular. There was no bruit over the liver but one was clearly heard over the chest 7 cm above the right costal margin midclavicularly. No cardiac murmurs were heard and chest X-ray was normal. Liver biopsy revealed hepatoma. These two cases had bruits over the chest but not over the liver though in both cases the livers were nodular and grossly
enlarged. Pavlica and Samuel,’ reporting 38 cases of hepatomas from Ethiopia, described no liver bruit, while in a later report from the same country Tsega" reported 100 cases of hepatoma and 80% of these had bruits. The fortuitous discovery of a bruit over the chest in case 1 prompted careful auscultation of the chest in all cases of suspected hepatomas, and one more patient with this physical sign was found within a 6-month period. It is possible therefore that bruits in the chest in cases of hepatoma may not be uncommon and this simple physical sign may prove to be of diagnostic value. Medical Faculty, Addis Ababa University, P.O. Box 1176, Addis Ababa,
Ethiopia
*Present address: Centre for
Respiratory Investigation, Royal Infirmary,
BAYU TEKLU* Glas-
gow G4 OSF
PLASMAPHERESIS IN SEVERE ASTHMA
Sip,—Dr Gartmann and co-workers (July 1, p. 40) report apparent benefit in a patient with chronic asthma after plasmapheresis. It is clearly important to establish that measured improvement in airflow obstruction is unequivocally due to the therapy concerned, and not to extraneous factors. In the report from Switzerland, firstly, no pretreatment lung function data are presented; secondly, no details are given of concurrent medication which might have influenced the spirometric data presented; thirdly, no account is taken of the effects of diurnal rhythm of airflow obstruction on the spirometric results;and, fourthly, no details of the environmental conditions during the period of observation are recorded. This last comment is particularly important, as it may be possible to explain the slow apparent improvement in the asthma of this atopic patient, and the reported concurrent fall in serum IgE, if she was away from her usual environment. As plasmapheresis is an expensive and technically difficult form of therapy and as the measured rate of response in this case (over a period of several weeks) is slower than that reported when the same technique is used to treat other conditions2-4 we feel that further well-documented reports of the 7. Pavlica, D., Samuel, I. Br. J. Cancer, 1970, 24, 22. 1. Clark, T. J. H., Hetzel, M. R. Br. J. Dis. Chest, 1977, 2. Lockwood, C. M., and others. Lancet, 1976, i, 711. 3. Verrier Jones, J., and others. ibid. 1976, i, 709. 4. Pinching, A. J., and others. ibid. 1976, ii, 1373.
71, 87.
of plasmapheresis in chronic severe asthma should be available before a formal controlled clinical trial is set up. use
Chest Unit, Churchill Hospital,
M. F. MUERS K. D. DAWKINS
Headington, Oxford OX3 7LJ
PROSTAGLANDINS AND SULPHASALAZINE
SIR,-Mr Moore and his colleagues (July 8, p. 98) suggest that the therapeutic action of sulphasalazine in the treatment of ulcerative colitis might be by inhibition of prostaglandin (P.G.) metabolism. We too have investigated the role of P.G. biosynthesis in the pathophysiology of ulcerative colitis but our results suggest that there is a significant inhibition of synthesis
by sulphasalazine. Using a radiometric method we have demonstrated that P.G. synthetase activities are high in rectal biopsy material from patients in the acute phase of ulcerative colitis and that these activities fall after successful treatment with sulphasalazine, prednisolone enemas, and codeine phosphate.’2 With this method we have examined the effects of these drugs on homogenates of human colonic
from an acute colitic underaffected tissue from a pagoing panproctocolectomy tient undergoing partial colectomy for polyposis coli. In homogenates from both sources neither prednisolone nor codeine phosphate had any effect on P.G. production at concentrations of 5-500 fl-mol;1. Sulphasalazine did, however, inhibit P.G. biosynthesis, although not as effectively as indomethacin. The I.c’50=for sulphasalazine was 251 mol/1 while that for indomethacin was 18.2 mol/1 (I.c’50=drug concentration required to produce 50% inhibition of p.G. production). Our results are in contrast to those of Moore et al. who found little or no inhibition of animal colonic P.G. synthesis, although they used lower doses. It is not easy to relate in-vitro results to the in-vivo situation because the colonic concentration of sulphasalazine is difficult to measure and may vary according to the dosage and frequency of ingestion. Further, sulphasalazine is bound by connective tissue3 and intraluminal concentrations may not reflect tissue levels. The therapeutic effects of sulphasalazine may be due to its major metabolites 5-aminosalicylic acid (5-A.s.A.) and sulphapyridine. 5-A.s.A. inhibits P.G. biosyilthesis’as does sulphapyridine.5 Clinically 5-A.s.A. is as effective as sulphasalazine in controlling acute ulcerative colitis when administered rectally.6 This is not inconsistent with the results of Moore et al. if the parent compound is an inhibitor of both P.G. synthesis and metabolism whereas 5-A.s.A. is inhibitory to synthesis mucosa
and
on
’
only. Moore et al. state that there is no evidence to suggest a beneficial role of P.G. synthetase inhibitors in ulcerative colitis. However, P.G. synthetase inhibitors have been used successfully in the treatment of radiation-induced colitis,’’ the diarrhoea of food intolerance allergies,8 and the irritable-bowel syndrome.9 In view of the evidence that P.G. production is raised in ulcerative colitis2 410 a therapeutic role for P.G. synthetase inhibitors remains a possibility. P. R. SMITH Department of Gastroenterolgy, General D. J. DAWSON City Hospital, Stoke-on-Trent ST4 6QG C. H. J. SWAN 1. Harris, D.W., Swan, C. H. J. Lancet, 1977, ii, 196. 2. Harris, D. W., Smith, P. R., Swan, C. H. J. Gut (in the press). 3. Hanngren, A., Hansson, E., Svartz, N., Ullberg, S. Acta med. scand. 1963,
173, 391. Gould, S. R. Lancet, 1975, ii, 988. Collier, H. O. J., Francis, A. A., McDonald-Gibson, W. J., Saeed, S. A. Prostaglandins, 1976, 11, 219. 6. Azad Khan, A. K., Piris, J., Truelove, S. C. Lancet, 1977, ii, 892. 7. Mennie, A. T, Dalley, V. M., Dineen, L. C., Collier, H. O. J. ibid. 1975, ii, 942. 8. Buisseret, P D., Youlten, L. J. F, Hemzelmann, D. I., Lessor, M. H ibid 1978, i, 906. 9 Rask-Madsen, J., Bukhave, K. Gut, 1978, 19, A448 10. Gould, S. R., Brash, A. R., Connelly, M. J. Lancet, 1977, ii, 98. 4. 5.
hepatoma. A 48-year-old Ethiopian man was admitted with a history of weight loss and anorexia for a month, and abdominal swelling for 10 weeks. He had slight icterus and the liver was 8 cm below the right costal margin, slightly tender, hard, and nodular. There was no bruit over the liver but one was clearly heard over the chest 7 cm above the right costal margin midclavicularly. No cardiac murmurs were heard and chest X-ray was normal. Liver biopsy revealed hepatoma. These two cases had bruits over the chest but not over the liver though in both cases the livers were nodular and grossly
enlarged. Pavlica and Samuel,’ reporting 38 cases of hepatomas from Ethiopia, described no liver bruit, while in a later report from the same country Tsega" reported 100 cases of hepatoma and 80% of these had bruits. The fortuitous discovery of a bruit over the chest in case 1 prompted careful auscultation of the chest in all cases of suspected hepatomas, and one more patient with this physical sign was found within a 6-month period. It is possible therefore that bruits in the chest in cases of hepatoma may not be uncommon and this simple physical sign may prove to be of diagnostic value. Medical Faculty, Addis Ababa University, P.O. Box 1176, Addis Ababa,
Ethiopia
*Present address: Centre for
Respiratory Investigation, Royal Infirmary,
BAYU TEKLU* Glas-
gow G4 OSF
PLASMAPHERESIS IN SEVERE ASTHMA
Sip,—Dr Gartmann and co-workers (July 1, p. 40) report apparent benefit in a patient with chronic asthma after plasmapheresis. It is clearly important to establish that measured improvement in airflow obstruction is unequivocally due to the therapy concerned, and not to extraneous factors. In the report from Switzerland, firstly, no pretreatment lung function data are presented; secondly, no details are given of concurrent medication which might have influenced the spirometric data presented; thirdly, no account is taken of the effects of diurnal rhythm of airflow obstruction on the spirometric results;and, fourthly, no details of the environmental conditions during the period of observation are recorded. This last comment is particularly important, as it may be possible to explain the slow apparent improvement in the asthma of this atopic patient, and the reported concurrent fall in serum IgE, if she was away from her usual environment. As plasmapheresis is an expensive and technically difficult form of therapy and as the measured rate of response in this case (over a period of several weeks) is slower than that reported when the same technique is used to treat other conditions2-4 we feel that further well-documented reports of the 7. Pavlica, D., Samuel, I. Br. J. Cancer, 1970, 24, 22. 1. Clark, T. J. H., Hetzel, M. R. Br. J. Dis. Chest, 1977, 2. Lockwood, C. M., and others. Lancet, 1976, i, 711. 3. Verrier Jones, J., and others. ibid. 1976, i, 709. 4. Pinching, A. J., and others. ibid. 1976, ii, 1373.
71, 87.
of plasmapheresis in chronic severe asthma should be available before a formal controlled clinical trial is set up. use
Chest Unit, Churchill Hospital,
M. F. MUERS K. D. DAWKINS
Headington, Oxford OX3 7LJ
PROSTAGLANDINS AND SULPHASALAZINE
SIR,-Mr Moore and his colleagues (July 8, p. 98) suggest that the therapeutic action of sulphasalazine in the treatment of ulcerative colitis might be by inhibition of prostaglandin (P.G.) metabolism. We too have investigated the role of P.G. biosynthesis in the pathophysiology of ulcerative colitis but our results suggest that there is a significant inhibition of synthesis
by sulphasalazine. Using a radiometric method we have demonstrated that P.G. synthetase activities are high in rectal biopsy material from patients in the acute phase of ulcerative colitis and that these activities fall after successful treatment with sulphasalazine, prednisolone enemas, and codeine phosphate.’2 With this method we have examined the effects of these drugs on homogenates of human colonic
from an acute colitic underaffected tissue from a pagoing panproctocolectomy tient undergoing partial colectomy for polyposis coli. In homogenates from both sources neither prednisolone nor codeine phosphate had any effect on P.G. production at concentrations of 5-500 fl-mol;1. Sulphasalazine did, however, inhibit P.G. biosynthesis, although not as effectively as indomethacin. The I.c’50=for sulphasalazine was 251 mol/1 while that for indomethacin was 18.2 mol/1 (I.c’50=drug concentration required to produce 50% inhibition of p.G. production). Our results are in contrast to those of Moore et al. who found little or no inhibition of animal colonic P.G. synthesis, although they used lower doses. It is not easy to relate in-vitro results to the in-vivo situation because the colonic concentration of sulphasalazine is difficult to measure and may vary according to the dosage and frequency of ingestion. Further, sulphasalazine is bound by connective tissue3 and intraluminal concentrations may not reflect tissue levels. The therapeutic effects of sulphasalazine may be due to its major metabolites 5-aminosalicylic acid (5-A.s.A.) and sulphapyridine. 5-A.s.A. inhibits P.G. biosyilthesis’as does sulphapyridine.5 Clinically 5-A.s.A. is as effective as sulphasalazine in controlling acute ulcerative colitis when administered rectally.6 This is not inconsistent with the results of Moore et al. if the parent compound is an inhibitor of both P.G. synthesis and metabolism whereas 5-A.s.A. is inhibitory to synthesis mucosa
and
on
’
only. Moore et al. state that there is no evidence to suggest a beneficial role of P.G. synthetase inhibitors in ulcerative colitis. However, P.G. synthetase inhibitors have been used successfully in the treatment of radiation-induced colitis,’’ the diarrhoea of food intolerance allergies,8 and the irritable-bowel syndrome.9 In view of the evidence that P.G. production is raised in ulcerative colitis2 410 a therapeutic role for P.G. synthetase inhibitors remains a possibility. P. R. SMITH Department of Gastroenterolgy, General D. J. DAWSON City Hospital, Stoke-on-Trent ST4 6QG C. H. J. SWAN 1. Harris, D.W., Swan, C. H. J. Lancet, 1977, ii, 196. 2. Harris, D. W., Smith, P. R., Swan, C. H. J. Gut (in the press). 3. Hanngren, A., Hansson, E., Svartz, N., Ullberg, S. Acta med. scand. 1963,
173, 391. Gould, S. R. Lancet, 1975, ii, 988. Collier, H. O. J., Francis, A. A., McDonald-Gibson, W. J., Saeed, S. A. Prostaglandins, 1976, 11, 219. 6. Azad Khan, A. K., Piris, J., Truelove, S. C. Lancet, 1977, ii, 892. 7. Mennie, A. T, Dalley, V. M., Dineen, L. C., Collier, H. O. J. ibid. 1975, ii, 942. 8. Buisseret, P D., Youlten, L. J. F, Hemzelmann, D. I., Lessor, M. H ibid 1978, i, 906. 9 Rask-Madsen, J., Bukhave, K. Gut, 1978, 19, A448 10. Gould, S. R., Brash, A. R., Connelly, M. J. Lancet, 1977, ii, 98. 4. 5.
