633
ENDOTHELIN-1 CONTENT IN PLASMA AND CSF OF PATIENTS WITH SUBARACHNOID HAEMORRHAGE
Coeliac disease SIR,-In their interesting and provocative study Dr O’Mahony and colleagues (June 23, p 1487) show that dermatitis herpetiformis whose biopsy specimen shows a normal small-intestine have pattern of intestinal humoral immunity akin to that in patients with coeliac disease, and they suggest that this is evidence for a two-stage model for the pathogenesis of coeliac disease. In support of their hypothesis they cite studies of putative latent coeliac disease in which dietary gluten loading has induced abnormalities of the small-intestinal mucosa. There is also persuasive epidemiological evidence for a causal role for environmental factors other than dietary gluten. Firstly, the existence of monozygotic twin pairs that are discordant for coeliac disease is well established.’ Reports that in some of these discordant twins coeliac disease developed in the other twin some years later serve to emphasise the role of these other factors The second piece of evidence is the sudden and pronounced decline in the incidence of coeliac disease in the UK in children born since 1976.3,4 The decline may be the result of changes in infant feeding practices that followed the Department of Health recommendations.5 Since 1975 there has been an increase in the proportion of mothers who breast feed, especially in proportion of those still breastfeeding at 6 weeks (24% in 1975,42% in 1980), and solid foods are being introduced later (in 1980 44% had started solids by 6 weeks compared with 40% in 1975).6Whether these changes are sufficient to account for a halving or more in incidence is debatable, but breastfeeding has proved protective in one case-control study.7 Less direct evidence is the poor correlation at a population level between the prevalence of HLA markers of genetic predisposition to coeliac disease and disease prevalence in countries where gluten-containing cereals are generally consumed.89 On the assumption that environmental factors, in addition to gluten, are necessary for the development of villous atrophy and that with gluten withdrawal the intestinal mucosa in some coeliacs becomes histologically normal then the identification of these factors might eventually allow some coeliacs to return safely to a normal diet.
patients a
Department of Public Health Medicine and Epidemiology, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK
R. F. A. LOGAN
J, Fischer R, Gebhardt B. Discordant occurrence of celiac disease in monozygotic twins. Klin Padiatr 1989; 201: 136-38 2 Salazar de Sousa J, Ramos de Almeida JM, Monteiro MV, Magalhaes Ramalho P. Late onset coeliac disease in the monozygotic twin of a coeliac child. Acta Paediatr Scand 1987, 76: 172-74. 3. Logan RFA, Rifkind EA, Busuttil A, Gilmour HM, Ferguson A. Prevalence and "incidence" of celiac disease in Edinburgh and the Lothian region of Scotland. 1 Henker
Gastroenterology 1986; 90: 334-42. 4. Langman MJS, McConnell TH, Spiegelhalter DJ, McConnell RB. Changing patterns of coeliac disease frequency: an analysis of coeliac society membership records Gut 1985; 26: 175-78. 5 Present-day practice in infant feeding. Report of a working party of the panel on child nutrition. Report on Health and Social Subjects no 9. London: HM Stationery
Results
as mean
(SD)
m
pg/ml NS= not significant
EDTA and endothelin-1was measured.3 We accumulated data on two groups of patients, according to whether or not vasospasm developed subsequently. We also separated data according to interval since SAH-within three days (pre-vasospasm), day 4-7 (initial vasospasm), or after day 8 (progression of vasospasm). For statistical comparisons we used Wilcoxon’s U test. We found endothelin in both plasma and CSF throughout the period of SAH (table). The plasma concentration was of the order of a few pg/ml, and did not change significantly before and during the period of vasospasm. Only in samples obtained after day 8 did the plasma level remain significantly higher (p < 0-05) in patients with vasospasm. In CSF the level of endothelin was about one-third that in plasma but there was no significant correlation with vasospasm. The endothelin level in plasma was in the same range as that reported previously,4 although agreement on the normal range has not yet been reached because of the variety of methods used. However, we found little correlation with the development of vasospasm, in contrast to the report by Masaoka et a1.5 The only significant difference, for plasma in the second week of SAH, might reflect a stress response in patients with cerebral vasospasm. Endothelin levels in CSF of psychiatric patients6 were much higher than we found, perhaps because of differences in methods and antibody specificity. We found endothelin in CSF but at levels significantly below those in plasma. There was no correlation with to The values obtained vasospasm. correspond 1 pmol/1, which is far below the concentration needed to contract a normal cerebral artery. There may be a mechanism that removes endothelin through the pulmonary or renal circulation so the circulating level might not always reflect the event at the site of a lesion. Endothelin probably acts via an autocrine or paracrine mechanism so that events may be limited to the lesion. We have demonstrated endothelin in the basilar artery endothelium in experimental vasospasm, using an immunohistochemical technique (unpublished). The presence of this peptide in both plasma and CSF supports endothelin synthesis in cerebral arteries after SAH.
Institute of Basic Medical Sciences, University of Tsukuba
AKIRA FUJIMORI MASASHI YANAGISAWA AKIRA SAITO KATSUTOSHI GOTO TOMOH MASAKI
Department of Neurosurgery, University of Tokyo
TATSUO MIMA KINTOMO TAKAKURA
Department of Neurosurgery, Saitama Medical Centre, Saitama Medical School, Saitama 350, Japan
TAKU SHIGENO
Office, 1974. 6 Martin J, Monk J. Infant feeding 1980. London: OPCS, 1982: 46-50. 7 Greco L, Auricchio S, Mayer M, Grimaldi M. Case-control study on nutritional risk factors in celiac disease. J Pediatr Gastroenterol Nutr 1988; 7: 395-99. 8. Dahan S, Slater PE, Cooper M, Brautbar C, Ashknazi A. Coeliac disease in the Rehovot-Ashdod region of Israel: incidence and ethnic distribution. J Epidemiol Community Health 1984; 34: 58-60. 9. Pittschieler K, Reissigl H, Mengarda G. Celiac disease in two different population groups of South Tirol. J Pediatr Gastroenterol Nutr 1988; 7: 400-02.
Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage SIR,-Endothelin may have a role in cerebral vasospasm after aneurysm rupture.’ We have measured endothelin concentrations in patients with subarachnoid haemorrhage (SAH). The patients had been admitted within 3 days of SAH and were operated on in the first week. At the time of surgery for ruptured cerebral aneurysms, we placed a catheter in the basal cistern and in the lateral ventricle to drain bloody CSF. Samples of venous blood and CSF were collected daily for 14 days after SAH. CSF 7 ml samples were collected in a tube containing 300 klU/ml aprotinin and 2 mg/ml
Yanagisawa M, Kurihara H, Kimura S, et al. A novel vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 322: 411-15. 2. Mima T, Yanagisawa M, Shigeno T, et al. Endothelin acts in cerebral arteries in vivo from the adventitial side. Stroke 1989; 20: 1553-56. 3. Suzuki N, Matsumoto H, Kitada C, Masaki T, Fujino M. A sensitive sandwichenzyme immunoassay for human endothelin. J Immunol Meth 1989; 118: 245-50. 4. Miyauchi T, Yanagisawa M, Tomizawa T, et al. Increased plasma concentrations of endothelin-1 and big endothelin-1 in acute myocardial infarction. Lancet 1989; ii: 1.
53-54. 5. Masaoka H, Suzuki R, Hirata Y, Emon T, Marumo F, Hirakawa K. Raised plasma endothelin in aneurysmal subarachnoid haemorrhage. Lancet 1989; ii: 1402. 6. Hoffman AM, Keiser HR, Grossman E, Godstein DS, Gold PW, Kling M. Endothelin concentrations in cerebrospinal fluid in depressive patients. Lancet 1989; ii: 1519.
ENDOTHELIN-1 CONTENT IN PLASMA AND CSF OF PATIENTS WITH SUBARACHNOID HAEMORRHAGE
Coeliac disease SIR,-In their interesting and provocative study Dr O’Mahony and colleagues (June 23, p 1487) show that dermatitis herpetiformis whose biopsy specimen shows a normal small-intestine have pattern of intestinal humoral immunity akin to that in patients with coeliac disease, and they suggest that this is evidence for a two-stage model for the pathogenesis of coeliac disease. In support of their hypothesis they cite studies of putative latent coeliac disease in which dietary gluten loading has induced abnormalities of the small-intestinal mucosa. There is also persuasive epidemiological evidence for a causal role for environmental factors other than dietary gluten. Firstly, the existence of monozygotic twin pairs that are discordant for coeliac disease is well established.’ Reports that in some of these discordant twins coeliac disease developed in the other twin some years later serve to emphasise the role of these other factors The second piece of evidence is the sudden and pronounced decline in the incidence of coeliac disease in the UK in children born since 1976.3,4 The decline may be the result of changes in infant feeding practices that followed the Department of Health recommendations.5 Since 1975 there has been an increase in the proportion of mothers who breast feed, especially in proportion of those still breastfeeding at 6 weeks (24% in 1975,42% in 1980), and solid foods are being introduced later (in 1980 44% had started solids by 6 weeks compared with 40% in 1975).6Whether these changes are sufficient to account for a halving or more in incidence is debatable, but breastfeeding has proved protective in one case-control study.7 Less direct evidence is the poor correlation at a population level between the prevalence of HLA markers of genetic predisposition to coeliac disease and disease prevalence in countries where gluten-containing cereals are generally consumed.89 On the assumption that environmental factors, in addition to gluten, are necessary for the development of villous atrophy and that with gluten withdrawal the intestinal mucosa in some coeliacs becomes histologically normal then the identification of these factors might eventually allow some coeliacs to return safely to a normal diet.
patients a
Department of Public Health Medicine and Epidemiology, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham NG7 2UH, UK
R. F. A. LOGAN
J, Fischer R, Gebhardt B. Discordant occurrence of celiac disease in monozygotic twins. Klin Padiatr 1989; 201: 136-38 2 Salazar de Sousa J, Ramos de Almeida JM, Monteiro MV, Magalhaes Ramalho P. Late onset coeliac disease in the monozygotic twin of a coeliac child. Acta Paediatr Scand 1987, 76: 172-74. 3. Logan RFA, Rifkind EA, Busuttil A, Gilmour HM, Ferguson A. Prevalence and "incidence" of celiac disease in Edinburgh and the Lothian region of Scotland. 1 Henker
Gastroenterology 1986; 90: 334-42. 4. Langman MJS, McConnell TH, Spiegelhalter DJ, McConnell RB. Changing patterns of coeliac disease frequency: an analysis of coeliac society membership records Gut 1985; 26: 175-78. 5 Present-day practice in infant feeding. Report of a working party of the panel on child nutrition. Report on Health and Social Subjects no 9. London: HM Stationery
Results
as mean
(SD)
m
pg/ml NS= not significant
EDTA and endothelin-1was measured.3 We accumulated data on two groups of patients, according to whether or not vasospasm developed subsequently. We also separated data according to interval since SAH-within three days (pre-vasospasm), day 4-7 (initial vasospasm), or after day 8 (progression of vasospasm). For statistical comparisons we used Wilcoxon’s U test. We found endothelin in both plasma and CSF throughout the period of SAH (table). The plasma concentration was of the order of a few pg/ml, and did not change significantly before and during the period of vasospasm. Only in samples obtained after day 8 did the plasma level remain significantly higher (p < 0-05) in patients with vasospasm. In CSF the level of endothelin was about one-third that in plasma but there was no significant correlation with vasospasm. The endothelin level in plasma was in the same range as that reported previously,4 although agreement on the normal range has not yet been reached because of the variety of methods used. However, we found little correlation with the development of vasospasm, in contrast to the report by Masaoka et a1.5 The only significant difference, for plasma in the second week of SAH, might reflect a stress response in patients with cerebral vasospasm. Endothelin levels in CSF of psychiatric patients6 were much higher than we found, perhaps because of differences in methods and antibody specificity. We found endothelin in CSF but at levels significantly below those in plasma. There was no correlation with to The values obtained vasospasm. correspond 1 pmol/1, which is far below the concentration needed to contract a normal cerebral artery. There may be a mechanism that removes endothelin through the pulmonary or renal circulation so the circulating level might not always reflect the event at the site of a lesion. Endothelin probably acts via an autocrine or paracrine mechanism so that events may be limited to the lesion. We have demonstrated endothelin in the basilar artery endothelium in experimental vasospasm, using an immunohistochemical technique (unpublished). The presence of this peptide in both plasma and CSF supports endothelin synthesis in cerebral arteries after SAH.
Institute of Basic Medical Sciences, University of Tsukuba
AKIRA FUJIMORI MASASHI YANAGISAWA AKIRA SAITO KATSUTOSHI GOTO TOMOH MASAKI
Department of Neurosurgery, University of Tokyo
TATSUO MIMA KINTOMO TAKAKURA
Department of Neurosurgery, Saitama Medical Centre, Saitama Medical School, Saitama 350, Japan
TAKU SHIGENO
Office, 1974. 6 Martin J, Monk J. Infant feeding 1980. London: OPCS, 1982: 46-50. 7 Greco L, Auricchio S, Mayer M, Grimaldi M. Case-control study on nutritional risk factors in celiac disease. J Pediatr Gastroenterol Nutr 1988; 7: 395-99. 8. Dahan S, Slater PE, Cooper M, Brautbar C, Ashknazi A. Coeliac disease in the Rehovot-Ashdod region of Israel: incidence and ethnic distribution. J Epidemiol Community Health 1984; 34: 58-60. 9. Pittschieler K, Reissigl H, Mengarda G. Celiac disease in two different population groups of South Tirol. J Pediatr Gastroenterol Nutr 1988; 7: 400-02.
Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage SIR,-Endothelin may have a role in cerebral vasospasm after aneurysm rupture.’ We have measured endothelin concentrations in patients with subarachnoid haemorrhage (SAH). The patients had been admitted within 3 days of SAH and were operated on in the first week. At the time of surgery for ruptured cerebral aneurysms, we placed a catheter in the basal cistern and in the lateral ventricle to drain bloody CSF. Samples of venous blood and CSF were collected daily for 14 days after SAH. CSF 7 ml samples were collected in a tube containing 300 klU/ml aprotinin and 2 mg/ml
Yanagisawa M, Kurihara H, Kimura S, et al. A novel vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 322: 411-15. 2. Mima T, Yanagisawa M, Shigeno T, et al. Endothelin acts in cerebral arteries in vivo from the adventitial side. Stroke 1989; 20: 1553-56. 3. Suzuki N, Matsumoto H, Kitada C, Masaki T, Fujino M. A sensitive sandwichenzyme immunoassay for human endothelin. J Immunol Meth 1989; 118: 245-50. 4. Miyauchi T, Yanagisawa M, Tomizawa T, et al. Increased plasma concentrations of endothelin-1 and big endothelin-1 in acute myocardial infarction. Lancet 1989; ii: 1.
53-54. 5. Masaoka H, Suzuki R, Hirata Y, Emon T, Marumo F, Hirakawa K. Raised plasma endothelin in aneurysmal subarachnoid haemorrhage. Lancet 1989; ii: 1402. 6. Hoffman AM, Keiser HR, Grossman E, Godstein DS, Gold PW, Kling M. Endothelin concentrations in cerebrospinal fluid in depressive patients. Lancet 1989; ii: 1519.
