1547
particular is charged with a global, rather than local or nationalistic, view, it is hard
what interests were served, save those of sentiment and appeasement of unelected lobbies such as the Catholic Church, by establishing as a right (at a time when the alarming trend of modem population growth was well established and documented) a freedom, that, as Emson points out, must be curtailed to ensure our survival. Many of us, like Emson, plead publicly for voluntary restraint to ease the population catastrophe. How many of us privately believe that voluntary restraint alone will do the trick? to see
British Organisation of Non-Parents, BM Box 5866, London WC1 N 3XX, UK
Is a
ROOT CARTWRIGHT
change in rabies vaccine schedule necessary for travellers?
SiR,—The 1992 edition of Immunisation against Infectious Disease’ has altered the recommended pre-exposure schedule for human diploid cell rabies vaccines (HDCV) from 2 doses one month apart, to 3 doses given at days 0, 7, and 28, as used in the USA. This change is presumably directed at those occupationally at risk from infection, but it will have serious practical implications for travellers. Pre-exposure vaccination had been taken by travellers for more than a decade (since the introduction of HDCV), coupled with advice on the need for rapid medical treatment, including post-exposure immunisation, after any potential rabies exposure.2 If a pre-exposure course has been received, fewer doses of post-exposure vaccine are required, rabies immunoglobulin (RIG) is deemed unnecessary, and any delay to the start of post-exposure prophylaxis could be less serious. Pre-travel immunisation against rabies is of particular value to individuals who travel to rabies endemic areas where suitable vaccines and RIG are not easily available or where there are doubts about the safety of local immunisation procedures. The pre-exposure course of vaccine is paid for by the travellers (animal handlers are a separate group entitled to free provision of the vaccine), who may now be asked to make an extra visit to the clinic or surgery and face an increase in cost of 50%. As a result, rabies immunisation uptake is likely to fall. Data on the efficacy of the 2-dose regimen come from two studies in the UK of 2435 recipients, which have demonstrated 98-100% seroconversion after 2 doses of HDCV given a month apart.3.’ Moreover, the manufacturers’ data sheet details the 2-dose course. It seems reasonable to continue to offer travellers this less costly and more practical schedule so as not to discourage the uptake of pre-travel rabies immunisation. Trailfinders, Immunisation Centre, London W8 7RG, UK
GIL LEA
concluded from these data that the pecentage of inheritance from either parent is other than 50%. In the St Mark’s Registry we found 30 cases of desmoid disease in 100 FAP families. Of these 30 patients, 16 (53%) inherited the APC gene from their fathers, with a 95% CI of 24-72%. In addition to desmoid diseases FAP patients are also at increased risk of developing hepatoblastoma,l thyroid,2 and upper gastrointestinal cancer.3 There were 3 documented cases of hepatoblastoma in our series which could have occurred in a gene carrier and in 2 of these the affected parent was the father. On reviewing previous publications, we found a further 32 cases of hepatoblastoma that developed in the children of FAP patients; 19 had an affected father. In view of our data and published data, 21 of 35 (60%) inherited the mutation from their father (95% CI 42-76). 3 cases of thyroid cancer and 11cases of upper gastrointestinal cancer were also ascertained from our series. In 1 case of thyroid cancer and in 6 cases of upper gastrointestinal cancer the mutation was inherited from the father. We can find little evidence for genomic imprinting in FAP. We thank the St Mark’s Polyposis Registry for data.
providing
Imperial Cancer Research Fund, Somatic Cell Genetics Laboratory, Lincoln’s Inn Fields, London WC2A 3PX, UK
STUART WHITELAW SHARON LOVE SHIRLEY HODGSON
some
of these
1. Giardello
FM, Offerhaus GJ, Krush AJ, et al. Risk of hepatoblastoma in familial adenomatous polyposis. J Pediatr 1991; 119: 766-68. 2. Plail RO, Glazer G, Thompson JPS, Bussey HJR. Adenomatous polyposis: an association with carcinoma of the thyroid? Br J Surg 1985; 72 (suppl): 138. 3. Sugihara K, Muto T, Kamiya J, Konishi F, Sawada T, Morioka Y. Gardner’s syndrome associated with periampullary carcinoma, duodenal and gastric adenomatosis. Dis Colon Rectum 1985; 25: 766-71.
ACE inhibitors for myocardial infarction and unstable angina SiR,—Your Nov 14 editorial is timely but fails to explore several possible reasons for the remarkable effect of angiotensinconverting-enzyme (ACE) inhibitors on myocardial infarction reported by Dr Yusuf and colleagues (Nov 14, p 1173) and the SAVE trial investigators.1 The findings of these studies add to the clinical evidence of a role for the renin-angiotensin system in myocardial infarction. A high renin relative to sodium profile increases the risk of myocardial infarction in hypertension.2 Furthermore, Cambien et a13 have shown that a deletion polymorphism in the gene for angiotensinconverting enzyme is a risk factor for myocardial infarction. In this case-control study, patients with myocardial infarction were more likely to be of the DD genotype (which is associated with serum ACE concentrations twice those found with the ID and II
Travel
Clinic, Hospital for Tropical Diseases, Queens House, London
genotypes). RON BEHRENS
Departments. Immunisation against infectious diseases. London: HM Stationery Office, 1992. 2. Furlong J, Lea G. Rabies prophylaxis simplified. Lancet 1981; i; 1311. 3. Turner GS, Nicholson KG, Tyrell DAJ, Aoki FY. Evaluation of a human diploid cell strain of rabies vaccine: final report of a three year study of pre-exposure immunisation. J Hyg Camb 1982; 89: 101-10. 4. Gardner SD. Prevention of rabies in man in England and Wales. Proceedings, Rabies a growing threat. Warwick, UK; 1983: 39-49. 1. UK Health
Familial adenomatous
polyposis and genomic imprinting
a!R,—Ms Lostelto and Dr Decosse (Oct 10, p 918) suggest
a
possible role for genomic imprinting in familial adenomatous polyposis (FAP), and use the presence of desmoid disease to assess intensity of phenotypic expression. They report that 62% of the 37 FAP patients with desmoid disease inherited the APC gene from their father. To obtain an idea of the percentage we would expect to find world wide if we took all patients with FAP and desmoid disease (let’s call this the true percentage), we can construct a confidence interval. The 95% CI for this percentage is 46-78; thus we would expect the true percentage of inheritance from the fathers to lie somewhere between 46% and 78%. Therefore it cannot be
The experimental evidence to which you allude is inconsistent and difficult to relate to the clinical picture.’ You make much of the effect of ACE inhibitors on the vascular response to injury, yet this seems to be species specific.5 Furthermore, although this model has possible relevance to angioplasty, how would a reduction in smooth muscle proliferation and intimal hyperplasia stabilise the atheromatous plaque? You also refer to ACE inhibitors inhibiting experimental atherosclerosis. The clinical relevance of these models is dubious, as are the drug concentrations used.4 Many hypotensive agents, including calcium antagonists, share this inhibitory effect.4 In any case, is it truly likely that, within 12 months, atheroma can be regressed sufficiently in 60-year-old men and women to reduce the rate of myocardial infarction by 25%? Is an effect on triggering mechanisms for infarction not more probable? Haemodynamic unloading, followed by reduction in myocardial oxygen consumption, is, as you propose, more likely to ameliorate chronic stable angina than unstable angina or myocardial infarction (both reduced in the SOLVD study). Yet, ACE inhibitors do not improve and may even, paradoxically, aggregate chronic angina.6 Is it not more likely that the haemodynamic mechanism might relate to reduction in coronary arterial shear stress and prevention of plaque rupture? Could ACE inhibitors, for example, reduce thrombosis? According to Harris,7 neuroendocrine activation in
particular is charged with a global, rather than local or nationalistic, view, it is hard
what interests were served, save those of sentiment and appeasement of unelected lobbies such as the Catholic Church, by establishing as a right (at a time when the alarming trend of modem population growth was well established and documented) a freedom, that, as Emson points out, must be curtailed to ensure our survival. Many of us, like Emson, plead publicly for voluntary restraint to ease the population catastrophe. How many of us privately believe that voluntary restraint alone will do the trick? to see
British Organisation of Non-Parents, BM Box 5866, London WC1 N 3XX, UK
Is a
ROOT CARTWRIGHT
change in rabies vaccine schedule necessary for travellers?
SiR,—The 1992 edition of Immunisation against Infectious Disease’ has altered the recommended pre-exposure schedule for human diploid cell rabies vaccines (HDCV) from 2 doses one month apart, to 3 doses given at days 0, 7, and 28, as used in the USA. This change is presumably directed at those occupationally at risk from infection, but it will have serious practical implications for travellers. Pre-exposure vaccination had been taken by travellers for more than a decade (since the introduction of HDCV), coupled with advice on the need for rapid medical treatment, including post-exposure immunisation, after any potential rabies exposure.2 If a pre-exposure course has been received, fewer doses of post-exposure vaccine are required, rabies immunoglobulin (RIG) is deemed unnecessary, and any delay to the start of post-exposure prophylaxis could be less serious. Pre-travel immunisation against rabies is of particular value to individuals who travel to rabies endemic areas where suitable vaccines and RIG are not easily available or where there are doubts about the safety of local immunisation procedures. The pre-exposure course of vaccine is paid for by the travellers (animal handlers are a separate group entitled to free provision of the vaccine), who may now be asked to make an extra visit to the clinic or surgery and face an increase in cost of 50%. As a result, rabies immunisation uptake is likely to fall. Data on the efficacy of the 2-dose regimen come from two studies in the UK of 2435 recipients, which have demonstrated 98-100% seroconversion after 2 doses of HDCV given a month apart.3.’ Moreover, the manufacturers’ data sheet details the 2-dose course. It seems reasonable to continue to offer travellers this less costly and more practical schedule so as not to discourage the uptake of pre-travel rabies immunisation. Trailfinders, Immunisation Centre, London W8 7RG, UK
GIL LEA
concluded from these data that the pecentage of inheritance from either parent is other than 50%. In the St Mark’s Registry we found 30 cases of desmoid disease in 100 FAP families. Of these 30 patients, 16 (53%) inherited the APC gene from their fathers, with a 95% CI of 24-72%. In addition to desmoid diseases FAP patients are also at increased risk of developing hepatoblastoma,l thyroid,2 and upper gastrointestinal cancer.3 There were 3 documented cases of hepatoblastoma in our series which could have occurred in a gene carrier and in 2 of these the affected parent was the father. On reviewing previous publications, we found a further 32 cases of hepatoblastoma that developed in the children of FAP patients; 19 had an affected father. In view of our data and published data, 21 of 35 (60%) inherited the mutation from their father (95% CI 42-76). 3 cases of thyroid cancer and 11cases of upper gastrointestinal cancer were also ascertained from our series. In 1 case of thyroid cancer and in 6 cases of upper gastrointestinal cancer the mutation was inherited from the father. We can find little evidence for genomic imprinting in FAP. We thank the St Mark’s Polyposis Registry for data.
providing
Imperial Cancer Research Fund, Somatic Cell Genetics Laboratory, Lincoln’s Inn Fields, London WC2A 3PX, UK
STUART WHITELAW SHARON LOVE SHIRLEY HODGSON
some
of these
1. Giardello
FM, Offerhaus GJ, Krush AJ, et al. Risk of hepatoblastoma in familial adenomatous polyposis. J Pediatr 1991; 119: 766-68. 2. Plail RO, Glazer G, Thompson JPS, Bussey HJR. Adenomatous polyposis: an association with carcinoma of the thyroid? Br J Surg 1985; 72 (suppl): 138. 3. Sugihara K, Muto T, Kamiya J, Konishi F, Sawada T, Morioka Y. Gardner’s syndrome associated with periampullary carcinoma, duodenal and gastric adenomatosis. Dis Colon Rectum 1985; 25: 766-71.
ACE inhibitors for myocardial infarction and unstable angina SiR,—Your Nov 14 editorial is timely but fails to explore several possible reasons for the remarkable effect of angiotensinconverting-enzyme (ACE) inhibitors on myocardial infarction reported by Dr Yusuf and colleagues (Nov 14, p 1173) and the SAVE trial investigators.1 The findings of these studies add to the clinical evidence of a role for the renin-angiotensin system in myocardial infarction. A high renin relative to sodium profile increases the risk of myocardial infarction in hypertension.2 Furthermore, Cambien et a13 have shown that a deletion polymorphism in the gene for angiotensinconverting enzyme is a risk factor for myocardial infarction. In this case-control study, patients with myocardial infarction were more likely to be of the DD genotype (which is associated with serum ACE concentrations twice those found with the ID and II
Travel
Clinic, Hospital for Tropical Diseases, Queens House, London
genotypes). RON BEHRENS
Departments. Immunisation against infectious diseases. London: HM Stationery Office, 1992. 2. Furlong J, Lea G. Rabies prophylaxis simplified. Lancet 1981; i; 1311. 3. Turner GS, Nicholson KG, Tyrell DAJ, Aoki FY. Evaluation of a human diploid cell strain of rabies vaccine: final report of a three year study of pre-exposure immunisation. J Hyg Camb 1982; 89: 101-10. 4. Gardner SD. Prevention of rabies in man in England and Wales. Proceedings, Rabies a growing threat. Warwick, UK; 1983: 39-49. 1. UK Health
Familial adenomatous
polyposis and genomic imprinting
a!R,—Ms Lostelto and Dr Decosse (Oct 10, p 918) suggest
a
possible role for genomic imprinting in familial adenomatous polyposis (FAP), and use the presence of desmoid disease to assess intensity of phenotypic expression. They report that 62% of the 37 FAP patients with desmoid disease inherited the APC gene from their father. To obtain an idea of the percentage we would expect to find world wide if we took all patients with FAP and desmoid disease (let’s call this the true percentage), we can construct a confidence interval. The 95% CI for this percentage is 46-78; thus we would expect the true percentage of inheritance from the fathers to lie somewhere between 46% and 78%. Therefore it cannot be
The experimental evidence to which you allude is inconsistent and difficult to relate to the clinical picture.’ You make much of the effect of ACE inhibitors on the vascular response to injury, yet this seems to be species specific.5 Furthermore, although this model has possible relevance to angioplasty, how would a reduction in smooth muscle proliferation and intimal hyperplasia stabilise the atheromatous plaque? You also refer to ACE inhibitors inhibiting experimental atherosclerosis. The clinical relevance of these models is dubious, as are the drug concentrations used.4 Many hypotensive agents, including calcium antagonists, share this inhibitory effect.4 In any case, is it truly likely that, within 12 months, atheroma can be regressed sufficiently in 60-year-old men and women to reduce the rate of myocardial infarction by 25%? Is an effect on triggering mechanisms for infarction not more probable? Haemodynamic unloading, followed by reduction in myocardial oxygen consumption, is, as you propose, more likely to ameliorate chronic stable angina than unstable angina or myocardial infarction (both reduced in the SOLVD study). Yet, ACE inhibitors do not improve and may even, paradoxically, aggregate chronic angina.6 Is it not more likely that the haemodynamic mechanism might relate to reduction in coronary arterial shear stress and prevention of plaque rupture? Could ACE inhibitors, for example, reduce thrombosis? According to Harris,7 neuroendocrine activation in
