- Email: [email protected]
cholesterol trial: clarifications
314
or other reasons for being at a comparable very high risk of CHD death)-will not be easy ... We need now to pull back our national policies directed at identifying and treating high blood cholesterol in the primary prevention setting and put on hold well-meant desires to intervene while we await convincing evidence
coronary disease
that the net effects will be beneficial". In the face of such serious misgivings, should we not warn our general public clearly against self-measurement of cholesterolindeed against routine cholesterol screening in any form? Shoppers in Boots can surely find better things to buy with their7.99. Those with very high CHD risk might consider investing in a few bottles of aspirin rather than a cholesterol test. Sheffield Hypertension Clinic, University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
L. E. RAMSAY W. W. YEO P. R. JACKSON
1. Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of serum cholesterol concentration: time to think again. BMJ 1991; 303: 953-57. 2. Royal College of General Practitioners Working Party. Guidelines for the management of hyperlipidaemia in general practice: towards the primary prevention of coronary heart disease (Occ Paper no 55)1. London: Royal College of General Practitioners, 1992. 3. Robertson I, Phillips A, Mant D, et al. Motivational effect of cholesterol measurement in general practice health checks. Br J Gen Pract 1992; 42: 469-72. 4. Bae C-Y, Keenan JM, Wenz J, McCaffrey DJ. A clinical trial of the American Heart Association step one diet for treatment of hypercholesterolemia. J Fam Pract 1991; 33: 249-54. 5. Schmidt JG. Cholesterol lowering treatment and mortality. BMJ 1992; 305: 1226-27. 6. Ravnskov U. Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. BMJ 1992; 305: 15-19. 7. Hulley SB, Walsh JMB, Newman TB. Health policy on blood cholesterol: time to change directions. Circulation 1992; 86: 1026-29. 8. Shaper AG, Pocock SJ, Phillips AN, Walker M. Identifying men at high risk of heart attacks: strategy for use in general practice. BMJ 1986; 293: 474-79.
allow calculation of the limits of agreement, and the agreement is poor despite high correlation coefficients: No of
Width of limits of
Ref
tests
agreement (mmol/L)
Correlation coefficient
3 4 5 6 6 7
53 80 105 228 261 352
1-30 (-0-81 to + 0-49) 1-20 (-0-82 to + 0-38) 1-77 (-0-87 to+0-90) 2-40 1.30 to +1’10) 2.80 ( - 0-80 to +2-00) 1-47 (-0-95 to +0-52)
0-96 0-97 0-97 0.81 0-80 0-95
a patient with a Reflotron cholesterol result of 5-00 would have a 95% probability of a laboratory result lying mmol/L in the range 4-62-5-82 mmol/L in the study with the narrowest limits of agreement and 3-00-5-80 mmol/L in the study with the widest.6 We cannot be certain which method is more accurate without proof of standardisation of the laboratory method but the results illustrate that Reflotron and laboratory methods of blood cholesterol measurement cannot be used interchangeably. The Boots kit has undergone very little evaluation but experience with the Reflotron/laboratory methods suggests grounds for concern about accuracy. The kit will need to be highly sensitive and specific if large numbers of false-positive and false-negative results leading to patients being made unnecessarily anxious or falsely reassured8 are to be avoided. We agree with your editorial that cholesterol testing should only be done as part of a comprehensive risk reduction strategy, ideally in the general practitioner’s surgery, using methods of measurement that give valid and reliable results.
For
example,
Departments of
Public Health Sciences and General Practice, St George’s Hospital Medical School, London SW17 ORE, UK
AZEEM MAJEED SEAN HILTON
1. Hilton S. Near
SiR,—Your editorial raises only some of the problems associated with the cholesterol testing kit. The most important is who should be tested. Serum total cholesterol alone is not a good indicator of the risk of heart disease; risk factors are multiplicative, not merely additive, and the total risk for an individual patient has to be considered. The Boots home testing kit can be used for large-scale unselective testing; although theoretically desirable, this has enormous financial implications. Some professional bodies have recommended unselective testing2,3 but in countries such as Britain, where a high proportion of the population have unacceptably high cholesterol concentrations,4 the financial burden of coping with hyperlipidaemia detected in this way would be astronomical. Surely it would be more sensible to target patients thought to be at increased risk of coronary heart disease.
Aust 1988; 149: 126-29.
Phillips S, Wyndham L, Shaw J, Walker SF. How accurately does the Reflotron dry-chemistry system measure plasma total cholesterol levels when used as a community screening device. MedJ Aust 1988; 149: 122-25. 5. Neil HAW, Cassidy DM, Laker MF, Alberti KGMM. Within-clinic reagent strip lipid measurement. Diab Med 1989; 6: 824-28. 6. Curzio JL, Howie C, Kennedy S, Reid JL, Fansh E, Barnes J Measurement of capillary cholesterol as an aid to the measurement of hypertensive patients with hyperlipidaemia: an assessment of the Reflotron. J Hum Hypertens 1992; 6: 185-88. 7. Majeed FA, Turner HJ, Stuart JM, Cooper RDO, Laite PA. Audit of near patient cholesterol testing in occupational health clinics. Occup Med (in press). 8. Kinlay S, Heller RF. Effectiveness and hazards of case finding for a high cholesterol concentration. BMJ 1990; 300: 1545-47.
4.
WHO clofibrate/cholesterol trial: clarifications
Department of Chemical Pathology, Newham General Hospital, London E14 8RU, UK
patient testing in general practice: a review. Br J Gen Pract 1990, 40: 32-36. 2. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; i: 307-10. 3. Kinlay S. Comparison of Reflotron and laboratory cholesterol measurements. Med J
S. BULUSU
1. Tunstall-Pedoe H. Who is for cholesterol testing. BMJ 1989; 298: 1593-94. 2. European Atherosclerosis Society Study Group. Strategies for the prevention of coronary heart disease: a policy statement of the European Atherosclerosis
Society. J 1987; 8: 77-88. Conference. blood cholesterol to Lowering prevent heart Development disease. JAMA 1985; 253: 2080-86. 4. Thelle DS, Shaper AG, Whitehead TP, Bullock DG, Ashby D, Patel I. Blood lipids in middle aged British men. Br Heart J 1983; 49: 205-13. Eur Heart
3. Consensus
SiR,—Advances in dry chemistry technology led to the introduction in the 1980s of desktop analysers capable of a range of biochemical tests.1 The market leader is the Reflotron (Boehringer Mannheim) which is most commonly used to measure blood cholesterol. The latest extension of this technology is the Boots home cholesterol testing kit. In clinical practice we need to compare any novel measurement technique with an established one to see if the new can replace the 01d.2 Most of the many comparisons of Reflotron desktop analysers with chemical pathology laboratory analysis have used inappropriate methods to measure agreement, using the correlation coefficient rather than the "limits of agreement" (mean difference :i:: 1 96 SD),2 Only five have contained sufficient information to
SIR,-Dr Heady and colleagues (Dec 5, p 1405) ask that a cause for the excess mortality in one prevention trial, and by inference other prevention trials of ischaemic heart disease, should receive serious scrutiny. Changes in attitude to lipid-lowering drugs benefit the pharmaceutical industry and the academic departments that they support. Use of so-called soft surrogate endpoints, such as the ability to lower serum cholesterol, allow the unwarranted assumption that lowering serum cholesterol concentrations decreases mortality. It seems a good time to halt the widespread use of various drugs and diets and consider physiological methods of reducing ischaemic heart disease, such as exercise and thyroid
replacement. Lord Taylor1 recollects that Bradford Hill taught that statistical treatment of the obvious was a waste of time, and my observations2 made the association of subclinical hypothyroidism and ischaemic heart disease seem self evident. Over the following decade, numerous cross-sectional studies were published showing no evidence that latent thyroid failure was a cause of coronary heart disease,3 but prospective studies on the same subjects4 after five years confirmed autoimmune thyroiditis as a separate risk factor for coronary heart disease. Cross-sectional mortality studies of coronary heart disease in subjects for whom the commonest cause of death is such disease make negative findings for a potent risk factor,
315
such as autoimmune thyroiditis, almost meaningless. The same distortion by selective mortality arises in studies on the association between subclinical hypothyroidism and hypercholesterolaemia. Groups of subjects with subclinical hypothyroidism often have normal serum cholesterol concentrations (those with high cholesterol have already died), whereas many groups with hypercholesterolaemia seem to have raised serum thyrotropin.5 Since more men than women are prone to coronary heart disease, selective mortality also explains the finding of thyroid antibodies confined to young men with angina in a population study done in Busselton, Western Australiaand confined to older women in a hospital population in Brussels.7 It should have been possible to anticipate that thyroid antibodies would be absent in centenarians, and this has now been conflITIled8 by a group that included Professor Pinchera who had sixteen years earlier shown that one-third of subjects with hypercholesterolaemia had latent hypothyroidism. A correlation has now been shown between serum thyrotropin concentrations and cholesterol within the normal range of thyroid function,9 and suppressive doses of thyroxine have a more beneficial effect on hypercholesterolaemia than lesser doses. A 5% reduction in the mean cholesterol concentration in the population could halve the prevalence of hypercholesterolaemia. Trials of D-thyroxine, inevitably contaminated with Lthyroxine, are irrelevant to primary prevention trials of Lthyroxine, and the concern about osteoporosis has proved unfounded (Dr Franklin and colleagues, July 4, p 9). A primary prevention trial of ischaemic heart disease with L-thyroxine should be delayed no longer. Charing Cross Hospital,
P. B. S. FOWLER
London W6 8RF, UK
1. Taylor S. Psychiatry and natural history. BMJ 1978; ii: 1754-58. 2. Fowler PBS. Lipid alterations in myxoedema and asymptomatic thyroiditis. Proceedings of the XVth international congress of therapeutics, Brussels. Amsterdam: Excerpta Medica, 1980; 1: 94-104. 3. Heinonen OP, Gordin A, Aho K, et al. Symptomless autoimmune thyroiditis in coronary heart disease. Lancet 1972; i: 785. 4. Baastenie PA, Vanhaelst L, Golstein J, et al. Asymptomatic autoimmune thyroiditis and coronary heart disease. Lancet 1977; ii: 155-58. 5. Ball MJ, Griffiths D, Thorogood M. Asymptomatic hypothyroidism and hypercholesterolaemia. J Soc Med 1991; 84: 527-29. 6. Mathews JD, Hooper BM, Ham S, et al. Association of auto-antibodies with smoking, cardiovascular morbidity and death in the Busselton population. Lancet 1973; ii: 754-58. 7. Bastenie PA, Vanhaelst L, Bonnyns M, et al. Pre-clinical hypothyroidism—a risk factor for coronary heart disease. Lancet 1971; i: 203-04. 8. Mariotti S, Sansoni P, Barbesino G, et al. Thyroid and other organs specific antibodies in healthy centenarians. Lancet 1992; 339: 1506-07. 9. Powell J, Alaghband-Zadeh J, Carter J, et al. Raised serum thyrotrophin in women with peripheral arterial disease. Br J Surg 1975; 74: 1139-41.
Arteriographic diagnosis of pulmonary embolism
on a
cardiac
care
unit
SIR,-Unless the diagnosis of pulmonary embolism is confirmed by puhnonary arteriography, acutely ill patients may receive inappropriate therapy.l.2 We report a patient with pulmonary embolism who was treated with streptokinase after the diagnosis was confirmed with equipment available on a cardiac care unit. A 59-year-old man was admitted with breathlessness and pleuritic right chest pain. He had a systolic blood pressure of 90 mm Hg, an elevated jugular venous pressure, and arterial hypoxaemia. Echocardiography demonstrated right-heart dilation with tricuspid regurgitation. Major pulmonary embolism was diagnosed and the patient was given heparin, but he remained hypotensive with poor urine output. An 8 French pigtail catheter and 0 035 inch guidewire were inserted into a vein via antecubital cutdown, and advanced into the pulmonary artery with use of a portable image intensifier. Manual injection of 10 mL non-ionic contrast into the proximal right pulmonary artery demonstrated
almost complete distal occlusion of the vessel (figure). Contrast injection into the left pulmonary artery demonstrated rapid clearance of contrast into the left lower lobe vessels, but no opacification of the left upper lobe artery. Attempted catheter dispersion of the right pulmonary artery embolus3 produced little arteriographic improvement. We therefore infused streptokinase into the proximal right pulmonary artery (250 000 U
Anteroposterior chest radiograph taken machine during manual injection of pulmonary artery.
with portable contrast into
X-ray right
30 min, followed by 100 000 U per hour to a total dose of 1 ’5 MU). On the next day his clinical condition had improved and pulmonary arteriography in the cardiac catheter laboratory demonstrated patency of all major branches of the right pulmonary artery. The left upper lobe pulmonary artery was occluded with filling defects in a segmental left lower lobe pulmonary artery. Manual injection of contrast under a portable image intensifier is not a substitute for formal pulmonary arteriography. Nevertheless, in our patient the technique readily confirmed the clinical diagnosis of major pulmonary embolism and infusion of streptokinase led to right pulmonary artery recanalisation. Many hospitals are experienced in pulmonary artery catheterisation, and portable image intensifiers are widely available. In hospitals without access to pulmonary arteriography, manual injection of contrast into the pulmonary circulation during radiographic screening may be useful in the acute management of suspected major pulmonary embolism. over
Department of Cardiology, Wythenshawe Hospital, Manchester M23 9LT, UK
ROBERT HENDERSON ANNIKA GRAHAM
1. Editorial. Thrombolysis for pulmonary embolism. Lancet 1992; 340: 21-22. 2. The PIOPED investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263: 2753-59. 3. Brady AJB, Crake T, Oakley CM. Percutaneous catheter fragmentation and distal dispersion of proximal pulmonary embolus. Lancet 1991; 338: 1186-89.
Clearance of HIV-1 viraemia after seroconversion SIR,-Dr Ariyoshi and colleagues (Nov 21, p 1257) suggest that clearance of cell-free virus in blood after primary HIV-1 infection is not mediated by neutralising antibodies, and that the cellular immune response to the HIV-1 p24 antigen may play some part early in infection. Complete understanding of this aspect may be central in the development of correct strategies for the immunoprophylaxis and immunotherapy of this infection, or to better understanding of the pathogenesis of AIDS. The data presented are essentially based on human HIV-1isolation and virus titration from plasma samples of 2 patients studied at seroconversion. Complete clearance of cell-free virus is demonstrated, although HIV-1 isolation from peripheral blood mononuclear cells (PBMCs) can be achieved at any time point.
or other reasons for being at a comparable very high risk of CHD death)-will not be easy ... We need now to pull back our national policies directed at identifying and treating high blood cholesterol in the primary prevention setting and put on hold well-meant desires to intervene while we await convincing evidence
coronary disease
that the net effects will be beneficial". In the face of such serious misgivings, should we not warn our general public clearly against self-measurement of cholesterolindeed against routine cholesterol screening in any form? Shoppers in Boots can surely find better things to buy with their7.99. Those with very high CHD risk might consider investing in a few bottles of aspirin rather than a cholesterol test. Sheffield Hypertension Clinic, University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
L. E. RAMSAY W. W. YEO P. R. JACKSON
1. Ramsay LE, Yeo WW, Jackson PR. Dietary reduction of serum cholesterol concentration: time to think again. BMJ 1991; 303: 953-57. 2. Royal College of General Practitioners Working Party. Guidelines for the management of hyperlipidaemia in general practice: towards the primary prevention of coronary heart disease (Occ Paper no 55)1. London: Royal College of General Practitioners, 1992. 3. Robertson I, Phillips A, Mant D, et al. Motivational effect of cholesterol measurement in general practice health checks. Br J Gen Pract 1992; 42: 469-72. 4. Bae C-Y, Keenan JM, Wenz J, McCaffrey DJ. A clinical trial of the American Heart Association step one diet for treatment of hypercholesterolemia. J Fam Pract 1991; 33: 249-54. 5. Schmidt JG. Cholesterol lowering treatment and mortality. BMJ 1992; 305: 1226-27. 6. Ravnskov U. Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. BMJ 1992; 305: 15-19. 7. Hulley SB, Walsh JMB, Newman TB. Health policy on blood cholesterol: time to change directions. Circulation 1992; 86: 1026-29. 8. Shaper AG, Pocock SJ, Phillips AN, Walker M. Identifying men at high risk of heart attacks: strategy for use in general practice. BMJ 1986; 293: 474-79.
allow calculation of the limits of agreement, and the agreement is poor despite high correlation coefficients: No of
Width of limits of
Ref
tests
agreement (mmol/L)
Correlation coefficient
3 4 5 6 6 7
53 80 105 228 261 352
1-30 (-0-81 to + 0-49) 1-20 (-0-82 to + 0-38) 1-77 (-0-87 to+0-90) 2-40 1.30 to +1’10) 2.80 ( - 0-80 to +2-00) 1-47 (-0-95 to +0-52)
0-96 0-97 0-97 0.81 0-80 0-95
a patient with a Reflotron cholesterol result of 5-00 would have a 95% probability of a laboratory result lying mmol/L in the range 4-62-5-82 mmol/L in the study with the narrowest limits of agreement and 3-00-5-80 mmol/L in the study with the widest.6 We cannot be certain which method is more accurate without proof of standardisation of the laboratory method but the results illustrate that Reflotron and laboratory methods of blood cholesterol measurement cannot be used interchangeably. The Boots kit has undergone very little evaluation but experience with the Reflotron/laboratory methods suggests grounds for concern about accuracy. The kit will need to be highly sensitive and specific if large numbers of false-positive and false-negative results leading to patients being made unnecessarily anxious or falsely reassured8 are to be avoided. We agree with your editorial that cholesterol testing should only be done as part of a comprehensive risk reduction strategy, ideally in the general practitioner’s surgery, using methods of measurement that give valid and reliable results.
For
example,
Departments of
Public Health Sciences and General Practice, St George’s Hospital Medical School, London SW17 ORE, UK
AZEEM MAJEED SEAN HILTON
1. Hilton S. Near
SiR,—Your editorial raises only some of the problems associated with the cholesterol testing kit. The most important is who should be tested. Serum total cholesterol alone is not a good indicator of the risk of heart disease; risk factors are multiplicative, not merely additive, and the total risk for an individual patient has to be considered. The Boots home testing kit can be used for large-scale unselective testing; although theoretically desirable, this has enormous financial implications. Some professional bodies have recommended unselective testing2,3 but in countries such as Britain, where a high proportion of the population have unacceptably high cholesterol concentrations,4 the financial burden of coping with hyperlipidaemia detected in this way would be astronomical. Surely it would be more sensible to target patients thought to be at increased risk of coronary heart disease.
Aust 1988; 149: 126-29.
Phillips S, Wyndham L, Shaw J, Walker SF. How accurately does the Reflotron dry-chemistry system measure plasma total cholesterol levels when used as a community screening device. MedJ Aust 1988; 149: 122-25. 5. Neil HAW, Cassidy DM, Laker MF, Alberti KGMM. Within-clinic reagent strip lipid measurement. Diab Med 1989; 6: 824-28. 6. Curzio JL, Howie C, Kennedy S, Reid JL, Fansh E, Barnes J Measurement of capillary cholesterol as an aid to the measurement of hypertensive patients with hyperlipidaemia: an assessment of the Reflotron. J Hum Hypertens 1992; 6: 185-88. 7. Majeed FA, Turner HJ, Stuart JM, Cooper RDO, Laite PA. Audit of near patient cholesterol testing in occupational health clinics. Occup Med (in press). 8. Kinlay S, Heller RF. Effectiveness and hazards of case finding for a high cholesterol concentration. BMJ 1990; 300: 1545-47.
4.
WHO clofibrate/cholesterol trial: clarifications
Department of Chemical Pathology, Newham General Hospital, London E14 8RU, UK
patient testing in general practice: a review. Br J Gen Pract 1990, 40: 32-36. 2. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986; i: 307-10. 3. Kinlay S. Comparison of Reflotron and laboratory cholesterol measurements. Med J
S. BULUSU
1. Tunstall-Pedoe H. Who is for cholesterol testing. BMJ 1989; 298: 1593-94. 2. European Atherosclerosis Society Study Group. Strategies for the prevention of coronary heart disease: a policy statement of the European Atherosclerosis
Society. J 1987; 8: 77-88. Conference. blood cholesterol to Lowering prevent heart Development disease. JAMA 1985; 253: 2080-86. 4. Thelle DS, Shaper AG, Whitehead TP, Bullock DG, Ashby D, Patel I. Blood lipids in middle aged British men. Br Heart J 1983; 49: 205-13. Eur Heart
3. Consensus
SiR,—Advances in dry chemistry technology led to the introduction in the 1980s of desktop analysers capable of a range of biochemical tests.1 The market leader is the Reflotron (Boehringer Mannheim) which is most commonly used to measure blood cholesterol. The latest extension of this technology is the Boots home cholesterol testing kit. In clinical practice we need to compare any novel measurement technique with an established one to see if the new can replace the 01d.2 Most of the many comparisons of Reflotron desktop analysers with chemical pathology laboratory analysis have used inappropriate methods to measure agreement, using the correlation coefficient rather than the "limits of agreement" (mean difference :i:: 1 96 SD),2 Only five have contained sufficient information to
SIR,-Dr Heady and colleagues (Dec 5, p 1405) ask that a cause for the excess mortality in one prevention trial, and by inference other prevention trials of ischaemic heart disease, should receive serious scrutiny. Changes in attitude to lipid-lowering drugs benefit the pharmaceutical industry and the academic departments that they support. Use of so-called soft surrogate endpoints, such as the ability to lower serum cholesterol, allow the unwarranted assumption that lowering serum cholesterol concentrations decreases mortality. It seems a good time to halt the widespread use of various drugs and diets and consider physiological methods of reducing ischaemic heart disease, such as exercise and thyroid
replacement. Lord Taylor1 recollects that Bradford Hill taught that statistical treatment of the obvious was a waste of time, and my observations2 made the association of subclinical hypothyroidism and ischaemic heart disease seem self evident. Over the following decade, numerous cross-sectional studies were published showing no evidence that latent thyroid failure was a cause of coronary heart disease,3 but prospective studies on the same subjects4 after five years confirmed autoimmune thyroiditis as a separate risk factor for coronary heart disease. Cross-sectional mortality studies of coronary heart disease in subjects for whom the commonest cause of death is such disease make negative findings for a potent risk factor,
315
such as autoimmune thyroiditis, almost meaningless. The same distortion by selective mortality arises in studies on the association between subclinical hypothyroidism and hypercholesterolaemia. Groups of subjects with subclinical hypothyroidism often have normal serum cholesterol concentrations (those with high cholesterol have already died), whereas many groups with hypercholesterolaemia seem to have raised serum thyrotropin.5 Since more men than women are prone to coronary heart disease, selective mortality also explains the finding of thyroid antibodies confined to young men with angina in a population study done in Busselton, Western Australiaand confined to older women in a hospital population in Brussels.7 It should have been possible to anticipate that thyroid antibodies would be absent in centenarians, and this has now been conflITIled8 by a group that included Professor Pinchera who had sixteen years earlier shown that one-third of subjects with hypercholesterolaemia had latent hypothyroidism. A correlation has now been shown between serum thyrotropin concentrations and cholesterol within the normal range of thyroid function,9 and suppressive doses of thyroxine have a more beneficial effect on hypercholesterolaemia than lesser doses. A 5% reduction in the mean cholesterol concentration in the population could halve the prevalence of hypercholesterolaemia. Trials of D-thyroxine, inevitably contaminated with Lthyroxine, are irrelevant to primary prevention trials of Lthyroxine, and the concern about osteoporosis has proved unfounded (Dr Franklin and colleagues, July 4, p 9). A primary prevention trial of ischaemic heart disease with L-thyroxine should be delayed no longer. Charing Cross Hospital,
P. B. S. FOWLER
London W6 8RF, UK
1. Taylor S. Psychiatry and natural history. BMJ 1978; ii: 1754-58. 2. Fowler PBS. Lipid alterations in myxoedema and asymptomatic thyroiditis. Proceedings of the XVth international congress of therapeutics, Brussels. Amsterdam: Excerpta Medica, 1980; 1: 94-104. 3. Heinonen OP, Gordin A, Aho K, et al. Symptomless autoimmune thyroiditis in coronary heart disease. Lancet 1972; i: 785. 4. Baastenie PA, Vanhaelst L, Golstein J, et al. Asymptomatic autoimmune thyroiditis and coronary heart disease. Lancet 1977; ii: 155-58. 5. Ball MJ, Griffiths D, Thorogood M. Asymptomatic hypothyroidism and hypercholesterolaemia. J Soc Med 1991; 84: 527-29. 6. Mathews JD, Hooper BM, Ham S, et al. Association of auto-antibodies with smoking, cardiovascular morbidity and death in the Busselton population. Lancet 1973; ii: 754-58. 7. Bastenie PA, Vanhaelst L, Bonnyns M, et al. Pre-clinical hypothyroidism—a risk factor for coronary heart disease. Lancet 1971; i: 203-04. 8. Mariotti S, Sansoni P, Barbesino G, et al. Thyroid and other organs specific antibodies in healthy centenarians. Lancet 1992; 339: 1506-07. 9. Powell J, Alaghband-Zadeh J, Carter J, et al. Raised serum thyrotrophin in women with peripheral arterial disease. Br J Surg 1975; 74: 1139-41.
Arteriographic diagnosis of pulmonary embolism
on a
cardiac
care
unit
SIR,-Unless the diagnosis of pulmonary embolism is confirmed by puhnonary arteriography, acutely ill patients may receive inappropriate therapy.l.2 We report a patient with pulmonary embolism who was treated with streptokinase after the diagnosis was confirmed with equipment available on a cardiac care unit. A 59-year-old man was admitted with breathlessness and pleuritic right chest pain. He had a systolic blood pressure of 90 mm Hg, an elevated jugular venous pressure, and arterial hypoxaemia. Echocardiography demonstrated right-heart dilation with tricuspid regurgitation. Major pulmonary embolism was diagnosed and the patient was given heparin, but he remained hypotensive with poor urine output. An 8 French pigtail catheter and 0 035 inch guidewire were inserted into a vein via antecubital cutdown, and advanced into the pulmonary artery with use of a portable image intensifier. Manual injection of 10 mL non-ionic contrast into the proximal right pulmonary artery demonstrated
almost complete distal occlusion of the vessel (figure). Contrast injection into the left pulmonary artery demonstrated rapid clearance of contrast into the left lower lobe vessels, but no opacification of the left upper lobe artery. Attempted catheter dispersion of the right pulmonary artery embolus3 produced little arteriographic improvement. We therefore infused streptokinase into the proximal right pulmonary artery (250 000 U
Anteroposterior chest radiograph taken machine during manual injection of pulmonary artery.
with portable contrast into
X-ray right
30 min, followed by 100 000 U per hour to a total dose of 1 ’5 MU). On the next day his clinical condition had improved and pulmonary arteriography in the cardiac catheter laboratory demonstrated patency of all major branches of the right pulmonary artery. The left upper lobe pulmonary artery was occluded with filling defects in a segmental left lower lobe pulmonary artery. Manual injection of contrast under a portable image intensifier is not a substitute for formal pulmonary arteriography. Nevertheless, in our patient the technique readily confirmed the clinical diagnosis of major pulmonary embolism and infusion of streptokinase led to right pulmonary artery recanalisation. Many hospitals are experienced in pulmonary artery catheterisation, and portable image intensifiers are widely available. In hospitals without access to pulmonary arteriography, manual injection of contrast into the pulmonary circulation during radiographic screening may be useful in the acute management of suspected major pulmonary embolism. over
Department of Cardiology, Wythenshawe Hospital, Manchester M23 9LT, UK
ROBERT HENDERSON ANNIKA GRAHAM
1. Editorial. Thrombolysis for pulmonary embolism. Lancet 1992; 340: 21-22. 2. The PIOPED investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990; 263: 2753-59. 3. Brady AJB, Crake T, Oakley CM. Percutaneous catheter fragmentation and distal dispersion of proximal pulmonary embolus. Lancet 1991; 338: 1186-89.
Clearance of HIV-1 viraemia after seroconversion SIR,-Dr Ariyoshi and colleagues (Nov 21, p 1257) suggest that clearance of cell-free virus in blood after primary HIV-1 infection is not mediated by neutralising antibodies, and that the cellular immune response to the HIV-1 p24 antigen may play some part early in infection. Complete understanding of this aspect may be central in the development of correct strategies for the immunoprophylaxis and immunotherapy of this infection, or to better understanding of the pathogenesis of AIDS. The data presented are essentially based on human HIV-1isolation and virus titration from plasma samples of 2 patients studied at seroconversion. Complete clearance of cell-free virus is demonstrated, although HIV-1 isolation from peripheral blood mononuclear cells (PBMCs) can be achieved at any time point.