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NATIVE KIDNEYS IN POST-TRANSPLANTATION HYPERTENSION
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patients with various forms of juvenile psychosis, including Rett syndrome, and suggested a correlation between this fragile site and a predisposition to infantile autism. We have looked for the Xp22 fragile site in 14 patients affected with Rett syndrome and their relatives. Lymphocytes cultures were exposed to FUdR3 and 100 metaphases were scored for each culture. The Xp22 fragile site was found, and at low frequency only, in 2 normal male relatives-namely, in the father in one family (in 2/100 metaphases) and in maternal grandfather in another (in 1/100 metaphases). It was not found in affected girls. Our findings do not support a relation between the Xp22 fragile site and Rett syndrome. Steinbach et al4 have described this fragile site in normal individuals, and in the classification of Sutherland5 Xp22 site is put among the common fragile sites. Molecular Genetics Istituto G. Gaslini,
Laboratory,
Genoa, Italy; Neurologisches Krankenhaus der Stadt, Vienna, Austria; 16148
Division of Neuropsychiatry, Istituto G. Gaslini; and Neurology Clinic, Bologna
N. ARCHIDIACONO A. RETT M. ROCCHI S. ROLANDO E. LUGARESI G. ROMEO
Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia and loss of purposeful hand use in girls: Rett’s syndrome: report of 35 cases. Ann Neurol 1983; 14: 471-79. 2. Gillberg C, Wahlström J, Hagberg B. Infantile autism and Rett’s syndrome: common 1.
chromosomal denominator. Lancet 1984; ii: 1094-95. 3 4
Filippi G, Ranaldi A, Archidiacono A, et al. Linkage between G6PD and fragile-X syndrome. Am JMed Genet 1985; 15: 116-19. Steinbach P, Barbi G, Boller T. On the frequency of telomeric chromosomal changes induced by culture conditions suitable for fragile X expression. Hum Genet 1982;
61: 160-62. 5. Sutherland GR, Parslow MI, Baker E. New classes of common fragile sites induced by 5-azacytidine and bromodeoxyuridine. Hum Genet 1985; 69: 233-37.
CORONARY ARTERY THROMBOSIS AND MYOCARDIAL INFARCTION
SIR,—Dr Stehbens’ hypothesis (Sept 21, p 639) on the relationship of coronary-artery thrombosis to myocardial infarction, whilst seemingly arriving at the correct conclusions, does not take into account some recent work. There is now considerable evidence that coronary thrombosis is a dynamic process1,2 and that it is usually associated with underlying plague fissuring of atheromatous plaques.2,3 Such thrombosis may be intraintimal, mural, or occlusive and may wax and wane. Furthermore, platelet microemboli have been found within the myocardial vasculature and these are usually associated with thrombosis and fissuring of the supplying epicardial The concept is not as new as Stehbens would coronary artery. 4,5 have us believe. Discussing the question of "infarction before thrombosis?" Stehbens cites Erhardt’s report of radioactivity within the entire thrombus after injection of 125 I-labelled fibrinogen. Had Erhardt done serial sections, as Fulton and Sumner did,he would have found that the head of the thrombus was radionegative, supporting "thrombosis before infarction". Stehbens states that "the role of thrombosis as an initiating factor in the development of myocardial infarction remains uncertain", citing Poole-Wilson and Warnes.7 In an effort to disclaim the role of thrombosis, they stated that in studies on sudden coronary death "thrombosis is not usually demonstrated in the coronary arteries at necropsy". The study referred to was a limited one of sudden death (70 cases in 13 years) with very rigid selection criteria for entry (personal communication); these criteria excluded all cases with any prodromal symptoms and criteria which are not apparent from the paper itself. Larger series, with cases with prodromal symptoms not severe enough to have presented to a doctor, have revealed a high incidence of acute intracoronary events in sudden death, mural thrombus, intraintimal thrombus, or plaque fissuring being present in some 95% of cases as against 1007o in age and sex matched controls.8 PooleWilson and Warnes’ statement that "thrombosis is only certain when a filling defect can be seen which is dissolved by thrombolytic therapy" also ignores recent clinicopathological studies describing
plaque
the characteristic angiographic appearances seen with acute coronary thrombosis. 9,10 Stehbens fails to recognise Falk’s work.1,3 Nor does he cite the excellent clinical work that supports his conclusions and has come from clinical thrombolysis studies in vivo." Indeed, Stehbens’ paper is surprising for the key references it omits. British Heart Foundation, Cardiovascular Pathology Unit, St George’s Hospital Medical School, London SW17 ORE
A. C. THOMAS
1. Falk E Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Circulation 1985; 71: 699-708. 2. Davies MJ, Thomas AC. Plaque fissuring-the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985; 53: 363-73. 3. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Br Heart J 1983; 50: 127-34. 4. Haerem JW. Mural platelet microthrombi and major acute lesions of main epicardial arteries in sudden death. Atherosclerosis 1974; 19: 529-41. 5. El-Maraghi N, Genton E. The relevance of platelet and fibrin thromboembolism of the coronary microcirculation with special reference to sudden cardiac death. Circulation 1980; 62: 936-44. 6. Fulton WFM, Sumner DJ. 125I-labelled fibrogen, autoradiography and stero-arteriography in identification of coronary thrombotic occlusion in fatal myocardial infarction. Br Heart J 1976; 38: 880. 7. Poole-Wilson PA, Warnes CA. Thrombosis in myocardial infarction. Lancet 1985; i: 749-50. 8. Davies MJ, Thomas A. Thrombosis and acute coronary artery lesions in sudden cardiac ischaemic death. N Engl J Med 1984; 310: 1137-40. 9. Levin DC, Fallon JT. Significance of the angiographic morphology of localised coronary stenoses: histopathological correlations. Circulation 1982; 66: 316-20. 10. Ambrose JA, Winters SL, Stern A, et al. Angiography morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol 1985; 5: 609-16. 11. Ganz W, Geft I, Shah PK, et al. Intravenous streptokinase in evolving acute myocardial infarction. Am J Cardiol 1984; 9: 1209-16.
NATIVE KIDNEYS IN POST-TRANSPLANTATION HYPERTENSION
SIR,—Curtis and colleagues (Oct 5, p 739) analyse 6 cases of native-kidney-dependent post-transplant hypertension. Hypertension was associated with a decreased renal allograft plasma flow. Nephrectomy decreased blood pressure and increased renal plasma flow by 77%. Since similar effects were observed after 2-3 days of captopril administration before nephrectomy, Curtis et al suggest that the native-kidney-dependent hypertension is mediated by the renin-angiotensin system. Interpretation of these results is difficult because all patients were hypotensive drugs, including frusemide, during the evaluation before nephrectomy but were off all medication during the postoperative assessment. This change might account, at least in part, for the haemodynamic changes observed. Furthermore, Curtis et al have also demonstrated (in their Am J Med paper 1985; 79: 193) decreased graft blood flow in all hypertensive patients, irrespective of the aetiology of the hypertension (renal artery stenosis and mild chronic rejection besides anephric transplanted patients). Might not prenephrectomy impaired graft blood flow be a consequence of the hypertensive disease per se or of its medical treatment rather than a specific consequence of abnormal endocrine behaviour of the native kidneys? Curtis et al suggest that native kidneys are a common cause of post-transplantation hypertension. We have reported (Adv Nephrol 1983; 12: 41) lasting hypertension in 65% and 50% of nonnephrectomised and nephrectomised patients, respectively, followed up for 7 years. The native kidneys thus seem to contribute to only about one-quarter (15% of the 65% frequency) of the cases hypertension in transplant recipients. The much higher proportion (about three-fifths of 21/33 patients) claimed by Curtis et al represents not proven native kidney hypertension but the proportion of post-transplant hypertensive patients in whom renal artery stenosis has been excluded by angiography and chronic rejection has been ruled out by an uneventful follow-up averaging 21 months. In our experience this negative evidence is insufficient to incriminate the native kidney in post-transplant hypertension. on
Department of Nephrology, Medical School,
University of Louvain, Cliniques Universitaires St-Luc, 1200 Brussels, Belgium
C. VAN YPERSELE DE STRIHOU
patients with various forms of juvenile psychosis, including Rett syndrome, and suggested a correlation between this fragile site and a predisposition to infantile autism. We have looked for the Xp22 fragile site in 14 patients affected with Rett syndrome and their relatives. Lymphocytes cultures were exposed to FUdR3 and 100 metaphases were scored for each culture. The Xp22 fragile site was found, and at low frequency only, in 2 normal male relatives-namely, in the father in one family (in 2/100 metaphases) and in maternal grandfather in another (in 1/100 metaphases). It was not found in affected girls. Our findings do not support a relation between the Xp22 fragile site and Rett syndrome. Steinbach et al4 have described this fragile site in normal individuals, and in the classification of Sutherland5 Xp22 site is put among the common fragile sites. Molecular Genetics Istituto G. Gaslini,
Laboratory,
Genoa, Italy; Neurologisches Krankenhaus der Stadt, Vienna, Austria; 16148
Division of Neuropsychiatry, Istituto G. Gaslini; and Neurology Clinic, Bologna
N. ARCHIDIACONO A. RETT M. ROCCHI S. ROLANDO E. LUGARESI G. ROMEO
Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia and loss of purposeful hand use in girls: Rett’s syndrome: report of 35 cases. Ann Neurol 1983; 14: 471-79. 2. Gillberg C, Wahlström J, Hagberg B. Infantile autism and Rett’s syndrome: common 1.
chromosomal denominator. Lancet 1984; ii: 1094-95. 3 4
Filippi G, Ranaldi A, Archidiacono A, et al. Linkage between G6PD and fragile-X syndrome. Am JMed Genet 1985; 15: 116-19. Steinbach P, Barbi G, Boller T. On the frequency of telomeric chromosomal changes induced by culture conditions suitable for fragile X expression. Hum Genet 1982;
61: 160-62. 5. Sutherland GR, Parslow MI, Baker E. New classes of common fragile sites induced by 5-azacytidine and bromodeoxyuridine. Hum Genet 1985; 69: 233-37.
CORONARY ARTERY THROMBOSIS AND MYOCARDIAL INFARCTION
SIR,—Dr Stehbens’ hypothesis (Sept 21, p 639) on the relationship of coronary-artery thrombosis to myocardial infarction, whilst seemingly arriving at the correct conclusions, does not take into account some recent work. There is now considerable evidence that coronary thrombosis is a dynamic process1,2 and that it is usually associated with underlying plague fissuring of atheromatous plaques.2,3 Such thrombosis may be intraintimal, mural, or occlusive and may wax and wane. Furthermore, platelet microemboli have been found within the myocardial vasculature and these are usually associated with thrombosis and fissuring of the supplying epicardial The concept is not as new as Stehbens would coronary artery. 4,5 have us believe. Discussing the question of "infarction before thrombosis?" Stehbens cites Erhardt’s report of radioactivity within the entire thrombus after injection of 125 I-labelled fibrinogen. Had Erhardt done serial sections, as Fulton and Sumner did,he would have found that the head of the thrombus was radionegative, supporting "thrombosis before infarction". Stehbens states that "the role of thrombosis as an initiating factor in the development of myocardial infarction remains uncertain", citing Poole-Wilson and Warnes.7 In an effort to disclaim the role of thrombosis, they stated that in studies on sudden coronary death "thrombosis is not usually demonstrated in the coronary arteries at necropsy". The study referred to was a limited one of sudden death (70 cases in 13 years) with very rigid selection criteria for entry (personal communication); these criteria excluded all cases with any prodromal symptoms and criteria which are not apparent from the paper itself. Larger series, with cases with prodromal symptoms not severe enough to have presented to a doctor, have revealed a high incidence of acute intracoronary events in sudden death, mural thrombus, intraintimal thrombus, or plaque fissuring being present in some 95% of cases as against 1007o in age and sex matched controls.8 PooleWilson and Warnes’ statement that "thrombosis is only certain when a filling defect can be seen which is dissolved by thrombolytic therapy" also ignores recent clinicopathological studies describing
plaque
the characteristic angiographic appearances seen with acute coronary thrombosis. 9,10 Stehbens fails to recognise Falk’s work.1,3 Nor does he cite the excellent clinical work that supports his conclusions and has come from clinical thrombolysis studies in vivo." Indeed, Stehbens’ paper is surprising for the key references it omits. British Heart Foundation, Cardiovascular Pathology Unit, St George’s Hospital Medical School, London SW17 ORE
A. C. THOMAS
1. Falk E Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Circulation 1985; 71: 699-708. 2. Davies MJ, Thomas AC. Plaque fissuring-the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J 1985; 53: 363-73. 3. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Br Heart J 1983; 50: 127-34. 4. Haerem JW. Mural platelet microthrombi and major acute lesions of main epicardial arteries in sudden death. Atherosclerosis 1974; 19: 529-41. 5. El-Maraghi N, Genton E. The relevance of platelet and fibrin thromboembolism of the coronary microcirculation with special reference to sudden cardiac death. Circulation 1980; 62: 936-44. 6. Fulton WFM, Sumner DJ. 125I-labelled fibrogen, autoradiography and stero-arteriography in identification of coronary thrombotic occlusion in fatal myocardial infarction. Br Heart J 1976; 38: 880. 7. Poole-Wilson PA, Warnes CA. Thrombosis in myocardial infarction. Lancet 1985; i: 749-50. 8. Davies MJ, Thomas A. Thrombosis and acute coronary artery lesions in sudden cardiac ischaemic death. N Engl J Med 1984; 310: 1137-40. 9. Levin DC, Fallon JT. Significance of the angiographic morphology of localised coronary stenoses: histopathological correlations. Circulation 1982; 66: 316-20. 10. Ambrose JA, Winters SL, Stern A, et al. Angiography morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol 1985; 5: 609-16. 11. Ganz W, Geft I, Shah PK, et al. Intravenous streptokinase in evolving acute myocardial infarction. Am J Cardiol 1984; 9: 1209-16.
NATIVE KIDNEYS IN POST-TRANSPLANTATION HYPERTENSION
SIR,—Curtis and colleagues (Oct 5, p 739) analyse 6 cases of native-kidney-dependent post-transplant hypertension. Hypertension was associated with a decreased renal allograft plasma flow. Nephrectomy decreased blood pressure and increased renal plasma flow by 77%. Since similar effects were observed after 2-3 days of captopril administration before nephrectomy, Curtis et al suggest that the native-kidney-dependent hypertension is mediated by the renin-angiotensin system. Interpretation of these results is difficult because all patients were hypotensive drugs, including frusemide, during the evaluation before nephrectomy but were off all medication during the postoperative assessment. This change might account, at least in part, for the haemodynamic changes observed. Furthermore, Curtis et al have also demonstrated (in their Am J Med paper 1985; 79: 193) decreased graft blood flow in all hypertensive patients, irrespective of the aetiology of the hypertension (renal artery stenosis and mild chronic rejection besides anephric transplanted patients). Might not prenephrectomy impaired graft blood flow be a consequence of the hypertensive disease per se or of its medical treatment rather than a specific consequence of abnormal endocrine behaviour of the native kidneys? Curtis et al suggest that native kidneys are a common cause of post-transplantation hypertension. We have reported (Adv Nephrol 1983; 12: 41) lasting hypertension in 65% and 50% of nonnephrectomised and nephrectomised patients, respectively, followed up for 7 years. The native kidneys thus seem to contribute to only about one-quarter (15% of the 65% frequency) of the cases hypertension in transplant recipients. The much higher proportion (about three-fifths of 21/33 patients) claimed by Curtis et al represents not proven native kidney hypertension but the proportion of post-transplant hypertensive patients in whom renal artery stenosis has been excluded by angiography and chronic rejection has been ruled out by an uneventful follow-up averaging 21 months. In our experience this negative evidence is insufficient to incriminate the native kidney in post-transplant hypertension. on
Department of Nephrology, Medical School,
University of Louvain, Cliniques Universitaires St-Luc, 1200 Brussels, Belgium
C. VAN YPERSELE DE STRIHOU