1075
Because of the ability of surgeons to communicate and the rapidity with which a new technique is mastered by surgeons, the lesson to be learned from this development is that research organisations and grant-giving bodies must be able to respond quickly to these developments. They must fund early prospective studies so that new techniques will pass muster or be rejected before many organisations have spent money on expensive and inappropriate machines such as the extracorporeal shockwave biliary lithotripsy device2 or even the laser used for gallbladder dissection in laparoscopic cholecystectomy.3 Perhaps, the saddest lesson for the British surgeons has been the complete lack of a British instrument-maker to supply equipment for this operation and the hard-sell techniques of the suppliers of foreign instruments in the UK. Middlesex Hospital, London W1N 8AA, UK
R. C. G. RUSSELL
1. Neugebauer E, Troidl H, Spangenberger W, Dietrich A, Lefering R. Cholecystectomy Study Group. Conventional versus laparoscopic cholecystectomy and the randomised controlled trial Br J Surg 1991; 78: 150-54. 2. Holohan TV. Laparoscopic cholecystectomy. Lancet 1991; 338: 801-03. 3. Southern Surgeons’ Club. A prospective analysis of 1518 laparoscopic cholecystectomies. N Engl J Med 1991; 325: 1073-78.
Metal stents in Budd-Chiari syndrome SIR,-Dr Weernink and colleagues (Sept 7, p 644) report placement of a Wallstent in the hepatic vein of a patient with Budd-Chiari syndrome, with good results. We believe that this is a logical technique that deserves further investigation, and report a 40-year-old housewife whom we believe was the first to receive a Gianturco metal stent in the inferior vena cava before mesocaval shunting.’ She remains well 31years later. However, it is important to establish clearly the extent of hepatocellular damage before undertaking such a conservative procedure, lest the presence of a metal stent in the hepatic veins or inferior vena cava jeopardises liver transplantation should hepatic failure develop, especially since this latter approach to management has proved very successful. Royal Free Hospital, London NW3 2QG, UK
ROBERT DICK K. E. H. HOBBS
,
Variation of aortic compliance with age and
pressure) is given as a mean (SD) Laogun and Goshng).
Irving D, Hobbs K. Dilatation of the inferior vena cava using an expandable metal stent in Budd-Chiari syndrome. J Hepatol 1991; 13: 149-51.
Measuring aortic distensibility SIR,-Dr Dart and colleagues (Aug 3, p 270) have used a method for assessing aortic distensibility which may be prone to error. The oscillation frequency of the ultrasound probe was not provided but at 4 MHz, which is typical for echocardiography, the maximum spatial resolution would be of the same order of magnitude as the change in aortic diameter being measured. This change would be much reduced in older individuals and in patients with arterial stiffening, making accurate measurements even more difficult. The reproducibility cited implies an ability to measure changes in aortic diameter of less than half the ultrasound wavelength used. We find this surprising. If aortic distensibility is to be assessed by measuring changes in aortic diameter during the cardiac cycle the most reliable approach would be a phase-locked loop technique.1 Magnetic resonance imaging2 can also be used but is expensive and not generally available. However, a problem with such techniques is that they provide a value for distensibility of the artery at a given section. Where patients are to be monitored repeatedly, relocation of the measurement point may prove difficult. Furthermore, focal lesions are formed in atherosclerosis, and distensibility measured at the site of such a lesion would not necessarily be the same as at a neighbouring, non-atherosclerotic site, further compounding the difficulties of follow-up studies. For these reasons, one of us (R. G. G.) described in 1976 a pulse-wave velocity doppler ultrasound technique based on the determination of the average compliance (distensibility) of the
for each age range
mm Hg pulse (modified from
aortic pathway. Hirai et al4 have observed that the abdominal aorta is especially sensitive for differentiating normal subjects from paticnts with coronary artery disease. Furthermore the abdominal aorta may be affected by atherosclerosis much earlier and more intensively than other arteries.5 Measurement of arterial wall compliance over both the descending thoracic and abdominal aorta makes this technique suitable for assessing susceptibility to atheromatous arterial disease as well as for monitoring response to therapy. The reproducibility of the technique has recently been evaluated6 and the approach has been used to investigate abnormal arterial behaviour in metabolic disorders, including diabetes mellitus,’ familial hypercholesterolaemia,8and Ehlers-Danlos and Marfan’s syndromes.9 In-vivo arterial wall compliance increases sharply with age in the first decade of life, reaching a peak at around 10 years." Thereafter compliance decreases with age (figure). It is not only the distensibility of the artery that is important (Aug 3 editorial) but also the stage of life at which it is observed.
descending
Divisions of
Radiological
Sciences and Medicine,
United Medical and Dental Schools, Guy’s and St Thomas’ Hospitals, London SE1 7EH, UK 1. Hokanson
E. D. LEHMANN R. G. GOSLING
DE, Mozersky DJ, Summer DS, Strandness DE Jr. A phase-locked echo
tracking 1 Gillams A, Dick R, Plans A,
sex.
0 = male; 8 = females. Compliance (C% per 10
system for
recording
arterial diameter
changes
in
vivo. J Appl Physiol
1972; 32: 728-33.
RH, Underwood SR, Bogren HG, et al. Regional aortic compliance studied by magnetic resonance imaging: the effects of age, training and coronary artery disease. Br Heart J 1989; 62: 90-96. 3. Gosling RG. Extraction of physiological information from spectrum analysed Doppler-shifted continuous-wave ultrasound signals. In: Hill PW, Watson BW, eds. IEE modem electronics monographs. Stevenage: Peter Peregrinus, 1976; 21:
2. Mohiaddin
73-125. 4. Hirai T, Sasayama S, Kawasaki T, Yagi S. Stiffness of systemic arteries in patients with myocardial infarction. Circulation 1989; 80: 78-86. 5. Manning PJ, Clarkson TB. Development, distribution, and lipid content of diet-induced atherosclerotic lesions of rhesus monkeys. Exp Mol Pathol 1972; 17: 38-54. 6. Wright JS, Cruikshank JK, Kontis S, Dore C, Gosling RG. Aortic compliance measured by non-invasive Doppler ultrasound: description of a method and its reproducibility. Clin Sci 1990; 78: 463-68. 7. Wahlqvist ML, Lo CS, Myers KA. Fish intake and arterial wall characteristics in healthy people and diabetic patients. Lancet 1989; ii: 944-46. 8. Lehmann ED, Fatemi-Langroudi B, Watts GF, Gosling RG. Arterial wall compliance in type I diabetes mellitus and familial hypercholesterolaemia. Diabetologia 1991; 34 (suppl 2): A166. 9. Handler CE, Child A, Light NM. Mitral valve prolapse, aortic compliance, and skin collagen in joint hypermobility syndrome. Br Heart J 1985; 54: 501-08. 10. Laogun AA, Gosling RG. In vivo arterial compliance in man. Clin Phys Physiol Meas 1982; 3: 201-12.
Injected corticosteroids in refractory asthma SIR,-We read your Aug 24 editorial (p 479) with concern and would advise caution about the interpretation of Ogirala and colleagues’ study of high-dose intramuscular triamcinolone acetonide (TA) in chronic severe asthma.1 The conclusion that high-dose TA was more effective than low-dose prednisolone was hardly surprising. TA is 10-15 times more potent than prednisolone in adrenalectomised rats, a "steroid sensitive" model, and may be more potent still in man, who is "steroid resistant".22
1076
This might explain why Ogirala steroidal side-effects with TA,
et
al
reported significantly more after only 3 months of
even
treatment.
You conclude that "Studies are now needed to show longer term benefits with respect to asthma and to the corticosteroid-induced side-effects". Useful data have already been published.2 Following the original year-long, double-blind, placebo-controlled, crossover study,3 review at 18 months revealed that only 10 of 22 patients continued on TA, and that the overall incidence of clinically apparent proximal myopathy was very high, at 28%.zOther major side-effects (bruising and weight loss) also became more frequent as TA therapy continued.3We subsequently learned that older clinicians in the UK had major reservations regarding TA, on the basis of similar clinical experiences in the 1960s, and that they had subsequently preferred prednisolone as the systemic steroid of choice. In the 1990s, high-dose inhaled steroid therapy alone is eminently suitable for most such patients with chronic severe asthma, and produces only a fraction of the side-effects.5-8 Department of Medicine, Royal Infirmary, Edinburgh EH3 9YW, UK Sandwell District General
SIMON CAPEWELL Hospital
DWIGHT MCLEOD
Ogirala RG, Aldrich TK, Presant DJ, et al High dose intramuscular triamcinolone in severe, chronic, life threatening asthma. N Engl J Med 1991, 324: 585-89. 2. Capewell S, McLeod DT, Seaton A. Systemic steroids in chronic severe asthma. Br Med J 1986; 293: 453. 3. McLeod DT, Capewell S, Law J, MacLaren W, Seaton A. Intramuscular triamcinolone acetonide in chronic severe asthma Thorax 1985; 40: 840-45. 4. Willey RF, Fergusson RJ, Godden DJ, Crompton GK, Grant IWB. Comparison of oral prednisolone and depot triamcinolone in patients with chronic severe asthma. Thorax 1984; 39: 340-44. 5. Smith MJ. The place of high dose inhaled corticosteroids in asthma therapy. Drugs 1987; 33: 423-29. 6. Ali NJ, Capewell S, Ward MJ. Bone turnover during high dose inhaled corticosteroid treatment. Thorax 1991; 46: 160-64. 7. Stead RJ, Cook NJ. Adverse effects of inhaled corticosteroids. Br Med J 1989; 298: 1.
403. 8. Salmeron S, Guerin JC, Godard P, et al. High doses of inhaled corticosteroids in unstable chronic asthma: a multicentre, double-blind, placebo-controlled study. Am Rev Respir Dis 1990; 140: 167-71.
Safety of IVIG made from HCV-antibodyscreened plasma SiR,—There has been some debate about the safety of removing HCV antibody (c100-3 specificity, as detected by first generation ELISA screening assays) from plasma pools destined for immunoglobulin production. Finlayson and Tankersley’ have argued that such antibody may be important in the prevention of hepatitis C virus (HCV) transmission, and that consequently it should not be omitted from source plasma pools until it can be shown that the safety of the target product (immunoglobulin) is not compromised. This is being investigated in animals. Other researchers2,3have argued that, since anti-HCV is a marker of infectivity, all antibody-positive donations should be excluded from fractionation pools, the deliberate inclusion of infective donations violating codes of good manufacturing practice. Since 1986 the immunology department at the Royal Children’s Hospital in Melbourne has been following children receiving intravenous immunoglobulin (IVIG, ’Intragam’, CSL) every four weeks. Most patients have hypogammaglobulinaemia or agammaglobulinaemia, although 1 child has Aldrich-Wiskott-like syndrome and 1 has severe combined immunodeficiency syndrome (SCID). Doses of IVIG varied from 3 to 24 g per visit. Routine investigations were monthly liver function tests, initiated to demonstrate the safety of intragam, a so-called third generation IVIG, consisting mainly of intact IgG molecules.4 In February, 1990, the National Blood Transfusion Committee introduced universal blood donor screening for HCV antibody in Australia. All immunoglobulin used in Australia is prepared from locally collected plasma and, because IVIG is usually in short supply, it was estimated that by May, 1990, all product on issue would have been produced from pools that were free of HCV antibody. We have analysed aspartate aminotransferase (AST) in 22 children on regular IVIG treatment before and after May, 1990.
21 children received IVIG before May, 1990. We took an AST value above the upper limit of our laboratory reference values (45 IU/1) on more than one occasion as being abnormal; 9 of the 21 children did not have this abnormality, 7 had an abnormality before but not after May 1990, and 5 did so both before and after May, 1990. 1 child, treated since May, 1990, has had raised AST values
both before and after IVIG was started. This child had SCID and has had a marrow transplant with probable graft-versus-host disease and Epstein-Barr virus infection postoperatively. Furthermore, this was the only child whose AST exceeded twice the upper limit on two or more occasions; AST has now returned to normal. The median number of AST estimations done before May, 1990, was 35 (range 4-45) and after this date was 15 (range 2-65). The findings in the children with a raised AST are not necessarily indicative ofnon-A, non-B hepatitis. In patients with non-A, non-B hepatitis and hypogammaglobulinaemia, AST values are often higher (mean 270 IU/1 in 5 patients5) and persistent; 10 of 12 had abnormal values after ten months.6 Transient minor increases in AST (< 100 IU/1) have been seen in a substantial proportion of hypogammaglobulinaemic patients receiving IVIG in whom liver function is assessed regularly.7 If we assume that normal AST values indicate the safety of intragam, our findings for AST values after May, 1990, indicate that the product made from HCV antibody-negative plasma is at least as safe as the previous product for which plasma donors were not screened for HCV antibody. Commonwealth Serum Laboratories, Parkville, 3052 Victoria, Australia, and Royal Children’s Hospital, Parkville
PETER SCHIFF ANDREW KEMP
Finlayson JS, Tankersley DL. Anti-HCV screening and plasma fractionation: the case against. Lancet 1990; 335: 1274-75. 2. Habibi B, Garretta M. Screening for hepatitis C virus antibody in plasma for 1.
fractionation. Lancet 1990; 335: 855-56. 3. Cash J. Screening for hepatitis C antibody in plasma for fractionation. Lancet 1990; 335: 1216. 4 Roberton DM, Hosking CS, Efthimiou H, et al. Decreased incidence of adverse infusion reactions in hypogammaglobulinaemic children receiving low pH intravenous immunoglobulin. Aust NZ J Med 1987; 17: 495-500. 5. Webster ANB, Lever AML. Non-A, non-B hepatitis after intravenous gammaglobulin. Lancet 1986; 335: 322 6. Lever AML, Brown D, Webster ADB, Thomas HC. Non-A, non-B hepatitis occurring in agammaglobulinaemic patients after intravenous immunoglobulin. Lancet 1984, ii. 1062. 7. Hany M, Ryan A, Webster ADB. Long-term safety and tolerability of intravenous immunoglobulin. Lancet 1991; 338: 194-95.
Prevalence of
benign prostatic hypertrophy
SIR,-Professor Garraway and colleagues (Aug 24, p 469) show a prevalence rate for benign prostatic hypertrophy (BPH) of 253 per 1000 men in the community aged between 40 and 79 years. They conclude, "thus apparently well men have a much higher frequency of BPH than was previously thought to be the case". Such a finding would have major implications for the provision of urological services, but unfortunately the data that they present have only limited relevance to service planning. The difficulty common to most epidemiological studies of disease frequency, is that the chosen definition of the condition does not reflect the probability of the individual benefiting from intervention. Garraway and colleagues’ definition of BPH includes prostatic weight, symptom score, and urinary peak flow rate, but it is unclear what relation these have to demand or need for treatment. What proportion of men with this definition of BPH need prostatectomy, or drugs, or continuous monitoring? Prostatectomy is generally accepted as the treatment of choice for BPH.1,2 The operation is typically carried out electively to relieve the symptoms of urinary outflow obstruction and thus improve quality of life. What is missing from Garroway and colleagues’ study is some assessment of how much the men investigated were affected by their symptoms. There are wide variations in the types and severity of symptoms that individual men are willing to tolerate. Studies have shown, for example, that one-third of healthy men accept symptoms of frequency, post-micturition dribbling, and weak stream as not needing special medical attention; that large
Because of the ability of surgeons to communicate and the rapidity with which a new technique is mastered by surgeons, the lesson to be learned from this development is that research organisations and grant-giving bodies must be able to respond quickly to these developments. They must fund early prospective studies so that new techniques will pass muster or be rejected before many organisations have spent money on expensive and inappropriate machines such as the extracorporeal shockwave biliary lithotripsy device2 or even the laser used for gallbladder dissection in laparoscopic cholecystectomy.3 Perhaps, the saddest lesson for the British surgeons has been the complete lack of a British instrument-maker to supply equipment for this operation and the hard-sell techniques of the suppliers of foreign instruments in the UK. Middlesex Hospital, London W1N 8AA, UK
R. C. G. RUSSELL
1. Neugebauer E, Troidl H, Spangenberger W, Dietrich A, Lefering R. Cholecystectomy Study Group. Conventional versus laparoscopic cholecystectomy and the randomised controlled trial Br J Surg 1991; 78: 150-54. 2. Holohan TV. Laparoscopic cholecystectomy. Lancet 1991; 338: 801-03. 3. Southern Surgeons’ Club. A prospective analysis of 1518 laparoscopic cholecystectomies. N Engl J Med 1991; 325: 1073-78.
Metal stents in Budd-Chiari syndrome SIR,-Dr Weernink and colleagues (Sept 7, p 644) report placement of a Wallstent in the hepatic vein of a patient with Budd-Chiari syndrome, with good results. We believe that this is a logical technique that deserves further investigation, and report a 40-year-old housewife whom we believe was the first to receive a Gianturco metal stent in the inferior vena cava before mesocaval shunting.’ She remains well 31years later. However, it is important to establish clearly the extent of hepatocellular damage before undertaking such a conservative procedure, lest the presence of a metal stent in the hepatic veins or inferior vena cava jeopardises liver transplantation should hepatic failure develop, especially since this latter approach to management has proved very successful. Royal Free Hospital, London NW3 2QG, UK
ROBERT DICK K. E. H. HOBBS
,
Variation of aortic compliance with age and
pressure) is given as a mean (SD) Laogun and Goshng).
Irving D, Hobbs K. Dilatation of the inferior vena cava using an expandable metal stent in Budd-Chiari syndrome. J Hepatol 1991; 13: 149-51.
Measuring aortic distensibility SIR,-Dr Dart and colleagues (Aug 3, p 270) have used a method for assessing aortic distensibility which may be prone to error. The oscillation frequency of the ultrasound probe was not provided but at 4 MHz, which is typical for echocardiography, the maximum spatial resolution would be of the same order of magnitude as the change in aortic diameter being measured. This change would be much reduced in older individuals and in patients with arterial stiffening, making accurate measurements even more difficult. The reproducibility cited implies an ability to measure changes in aortic diameter of less than half the ultrasound wavelength used. We find this surprising. If aortic distensibility is to be assessed by measuring changes in aortic diameter during the cardiac cycle the most reliable approach would be a phase-locked loop technique.1 Magnetic resonance imaging2 can also be used but is expensive and not generally available. However, a problem with such techniques is that they provide a value for distensibility of the artery at a given section. Where patients are to be monitored repeatedly, relocation of the measurement point may prove difficult. Furthermore, focal lesions are formed in atherosclerosis, and distensibility measured at the site of such a lesion would not necessarily be the same as at a neighbouring, non-atherosclerotic site, further compounding the difficulties of follow-up studies. For these reasons, one of us (R. G. G.) described in 1976 a pulse-wave velocity doppler ultrasound technique based on the determination of the average compliance (distensibility) of the
for each age range
mm Hg pulse (modified from
aortic pathway. Hirai et al4 have observed that the abdominal aorta is especially sensitive for differentiating normal subjects from paticnts with coronary artery disease. Furthermore the abdominal aorta may be affected by atherosclerosis much earlier and more intensively than other arteries.5 Measurement of arterial wall compliance over both the descending thoracic and abdominal aorta makes this technique suitable for assessing susceptibility to atheromatous arterial disease as well as for monitoring response to therapy. The reproducibility of the technique has recently been evaluated6 and the approach has been used to investigate abnormal arterial behaviour in metabolic disorders, including diabetes mellitus,’ familial hypercholesterolaemia,8and Ehlers-Danlos and Marfan’s syndromes.9 In-vivo arterial wall compliance increases sharply with age in the first decade of life, reaching a peak at around 10 years." Thereafter compliance decreases with age (figure). It is not only the distensibility of the artery that is important (Aug 3 editorial) but also the stage of life at which it is observed.
descending
Divisions of
Radiological
Sciences and Medicine,
United Medical and Dental Schools, Guy’s and St Thomas’ Hospitals, London SE1 7EH, UK 1. Hokanson
E. D. LEHMANN R. G. GOSLING
DE, Mozersky DJ, Summer DS, Strandness DE Jr. A phase-locked echo
tracking 1 Gillams A, Dick R, Plans A,
sex.
0 = male; 8 = females. Compliance (C% per 10
system for
recording
arterial diameter
changes
in
vivo. J Appl Physiol
1972; 32: 728-33.
RH, Underwood SR, Bogren HG, et al. Regional aortic compliance studied by magnetic resonance imaging: the effects of age, training and coronary artery disease. Br Heart J 1989; 62: 90-96. 3. Gosling RG. Extraction of physiological information from spectrum analysed Doppler-shifted continuous-wave ultrasound signals. In: Hill PW, Watson BW, eds. IEE modem electronics monographs. Stevenage: Peter Peregrinus, 1976; 21:
2. Mohiaddin
73-125. 4. Hirai T, Sasayama S, Kawasaki T, Yagi S. Stiffness of systemic arteries in patients with myocardial infarction. Circulation 1989; 80: 78-86. 5. Manning PJ, Clarkson TB. Development, distribution, and lipid content of diet-induced atherosclerotic lesions of rhesus monkeys. Exp Mol Pathol 1972; 17: 38-54. 6. Wright JS, Cruikshank JK, Kontis S, Dore C, Gosling RG. Aortic compliance measured by non-invasive Doppler ultrasound: description of a method and its reproducibility. Clin Sci 1990; 78: 463-68. 7. Wahlqvist ML, Lo CS, Myers KA. Fish intake and arterial wall characteristics in healthy people and diabetic patients. Lancet 1989; ii: 944-46. 8. Lehmann ED, Fatemi-Langroudi B, Watts GF, Gosling RG. Arterial wall compliance in type I diabetes mellitus and familial hypercholesterolaemia. Diabetologia 1991; 34 (suppl 2): A166. 9. Handler CE, Child A, Light NM. Mitral valve prolapse, aortic compliance, and skin collagen in joint hypermobility syndrome. Br Heart J 1985; 54: 501-08. 10. Laogun AA, Gosling RG. In vivo arterial compliance in man. Clin Phys Physiol Meas 1982; 3: 201-12.
Injected corticosteroids in refractory asthma SIR,-We read your Aug 24 editorial (p 479) with concern and would advise caution about the interpretation of Ogirala and colleagues’ study of high-dose intramuscular triamcinolone acetonide (TA) in chronic severe asthma.1 The conclusion that high-dose TA was more effective than low-dose prednisolone was hardly surprising. TA is 10-15 times more potent than prednisolone in adrenalectomised rats, a "steroid sensitive" model, and may be more potent still in man, who is "steroid resistant".22
1076
This might explain why Ogirala steroidal side-effects with TA,
et
al
reported significantly more after only 3 months of
even
treatment.
You conclude that "Studies are now needed to show longer term benefits with respect to asthma and to the corticosteroid-induced side-effects". Useful data have already been published.2 Following the original year-long, double-blind, placebo-controlled, crossover study,3 review at 18 months revealed that only 10 of 22 patients continued on TA, and that the overall incidence of clinically apparent proximal myopathy was very high, at 28%.zOther major side-effects (bruising and weight loss) also became more frequent as TA therapy continued.3We subsequently learned that older clinicians in the UK had major reservations regarding TA, on the basis of similar clinical experiences in the 1960s, and that they had subsequently preferred prednisolone as the systemic steroid of choice. In the 1990s, high-dose inhaled steroid therapy alone is eminently suitable for most such patients with chronic severe asthma, and produces only a fraction of the side-effects.5-8 Department of Medicine, Royal Infirmary, Edinburgh EH3 9YW, UK Sandwell District General
SIMON CAPEWELL Hospital
DWIGHT MCLEOD
Ogirala RG, Aldrich TK, Presant DJ, et al High dose intramuscular triamcinolone in severe, chronic, life threatening asthma. N Engl J Med 1991, 324: 585-89. 2. Capewell S, McLeod DT, Seaton A. Systemic steroids in chronic severe asthma. Br Med J 1986; 293: 453. 3. McLeod DT, Capewell S, Law J, MacLaren W, Seaton A. Intramuscular triamcinolone acetonide in chronic severe asthma Thorax 1985; 40: 840-45. 4. Willey RF, Fergusson RJ, Godden DJ, Crompton GK, Grant IWB. Comparison of oral prednisolone and depot triamcinolone in patients with chronic severe asthma. Thorax 1984; 39: 340-44. 5. Smith MJ. The place of high dose inhaled corticosteroids in asthma therapy. Drugs 1987; 33: 423-29. 6. Ali NJ, Capewell S, Ward MJ. Bone turnover during high dose inhaled corticosteroid treatment. Thorax 1991; 46: 160-64. 7. Stead RJ, Cook NJ. Adverse effects of inhaled corticosteroids. Br Med J 1989; 298: 1.
403. 8. Salmeron S, Guerin JC, Godard P, et al. High doses of inhaled corticosteroids in unstable chronic asthma: a multicentre, double-blind, placebo-controlled study. Am Rev Respir Dis 1990; 140: 167-71.
Safety of IVIG made from HCV-antibodyscreened plasma SiR,—There has been some debate about the safety of removing HCV antibody (c100-3 specificity, as detected by first generation ELISA screening assays) from plasma pools destined for immunoglobulin production. Finlayson and Tankersley’ have argued that such antibody may be important in the prevention of hepatitis C virus (HCV) transmission, and that consequently it should not be omitted from source plasma pools until it can be shown that the safety of the target product (immunoglobulin) is not compromised. This is being investigated in animals. Other researchers2,3have argued that, since anti-HCV is a marker of infectivity, all antibody-positive donations should be excluded from fractionation pools, the deliberate inclusion of infective donations violating codes of good manufacturing practice. Since 1986 the immunology department at the Royal Children’s Hospital in Melbourne has been following children receiving intravenous immunoglobulin (IVIG, ’Intragam’, CSL) every four weeks. Most patients have hypogammaglobulinaemia or agammaglobulinaemia, although 1 child has Aldrich-Wiskott-like syndrome and 1 has severe combined immunodeficiency syndrome (SCID). Doses of IVIG varied from 3 to 24 g per visit. Routine investigations were monthly liver function tests, initiated to demonstrate the safety of intragam, a so-called third generation IVIG, consisting mainly of intact IgG molecules.4 In February, 1990, the National Blood Transfusion Committee introduced universal blood donor screening for HCV antibody in Australia. All immunoglobulin used in Australia is prepared from locally collected plasma and, because IVIG is usually in short supply, it was estimated that by May, 1990, all product on issue would have been produced from pools that were free of HCV antibody. We have analysed aspartate aminotransferase (AST) in 22 children on regular IVIG treatment before and after May, 1990.
21 children received IVIG before May, 1990. We took an AST value above the upper limit of our laboratory reference values (45 IU/1) on more than one occasion as being abnormal; 9 of the 21 children did not have this abnormality, 7 had an abnormality before but not after May 1990, and 5 did so both before and after May, 1990. 1 child, treated since May, 1990, has had raised AST values
both before and after IVIG was started. This child had SCID and has had a marrow transplant with probable graft-versus-host disease and Epstein-Barr virus infection postoperatively. Furthermore, this was the only child whose AST exceeded twice the upper limit on two or more occasions; AST has now returned to normal. The median number of AST estimations done before May, 1990, was 35 (range 4-45) and after this date was 15 (range 2-65). The findings in the children with a raised AST are not necessarily indicative ofnon-A, non-B hepatitis. In patients with non-A, non-B hepatitis and hypogammaglobulinaemia, AST values are often higher (mean 270 IU/1 in 5 patients5) and persistent; 10 of 12 had abnormal values after ten months.6 Transient minor increases in AST (< 100 IU/1) have been seen in a substantial proportion of hypogammaglobulinaemic patients receiving IVIG in whom liver function is assessed regularly.7 If we assume that normal AST values indicate the safety of intragam, our findings for AST values after May, 1990, indicate that the product made from HCV antibody-negative plasma is at least as safe as the previous product for which plasma donors were not screened for HCV antibody. Commonwealth Serum Laboratories, Parkville, 3052 Victoria, Australia, and Royal Children’s Hospital, Parkville
PETER SCHIFF ANDREW KEMP
Finlayson JS, Tankersley DL. Anti-HCV screening and plasma fractionation: the case against. Lancet 1990; 335: 1274-75. 2. Habibi B, Garretta M. Screening for hepatitis C virus antibody in plasma for 1.
fractionation. Lancet 1990; 335: 855-56. 3. Cash J. Screening for hepatitis C antibody in plasma for fractionation. Lancet 1990; 335: 1216. 4 Roberton DM, Hosking CS, Efthimiou H, et al. Decreased incidence of adverse infusion reactions in hypogammaglobulinaemic children receiving low pH intravenous immunoglobulin. Aust NZ J Med 1987; 17: 495-500. 5. Webster ANB, Lever AML. Non-A, non-B hepatitis after intravenous gammaglobulin. Lancet 1986; 335: 322 6. Lever AML, Brown D, Webster ADB, Thomas HC. Non-A, non-B hepatitis occurring in agammaglobulinaemic patients after intravenous immunoglobulin. Lancet 1984, ii. 1062. 7. Hany M, Ryan A, Webster ADB. Long-term safety and tolerability of intravenous immunoglobulin. Lancet 1991; 338: 194-95.
Prevalence of
benign prostatic hypertrophy
SIR,-Professor Garraway and colleagues (Aug 24, p 469) show a prevalence rate for benign prostatic hypertrophy (BPH) of 253 per 1000 men in the community aged between 40 and 79 years. They conclude, "thus apparently well men have a much higher frequency of BPH than was previously thought to be the case". Such a finding would have major implications for the provision of urological services, but unfortunately the data that they present have only limited relevance to service planning. The difficulty common to most epidemiological studies of disease frequency, is that the chosen definition of the condition does not reflect the probability of the individual benefiting from intervention. Garraway and colleagues’ definition of BPH includes prostatic weight, symptom score, and urinary peak flow rate, but it is unclear what relation these have to demand or need for treatment. What proportion of men with this definition of BPH need prostatectomy, or drugs, or continuous monitoring? Prostatectomy is generally accepted as the treatment of choice for BPH.1,2 The operation is typically carried out electively to relieve the symptoms of urinary outflow obstruction and thus improve quality of life. What is missing from Garroway and colleagues’ study is some assessment of how much the men investigated were affected by their symptoms. There are wide variations in the types and severity of symptoms that individual men are willing to tolerate. Studies have shown, for example, that one-third of healthy men accept symptoms of frequency, post-micturition dribbling, and weak stream as not needing special medical attention; that large
