- Email: [email protected]
Rapid diagnosis of myocardial infarction by immunoturbidimetric myoglobin measurement
1343
vascular lesions.2-4 Thus the phenotypes of the
two
mutations
overlap and both include cerebrovascular and brain parenchymal lesions. A very high proportion of patients with dementia have a mixed vascular and Alzheimer pathology. While this may reflect dual pathology it could, in some cases, be part of an extended spectrum of
expression of 0-amyloid disease involving angiopathy. AD is aetiologically heterogeneous5 and genetic factors and head injury are risk factors. This heterogeneity may also contribute to the variation in clinicopathological findings. This story mirrors experience with prion diseases in which the identification of pathogenic mutants led to the realisation that the disease phenotype was very variable.7 Clinical and pathological diagnosis of AD remains important but classification by such means is of limited value. It may be premature to suggest that the term "Alzheimer’s disease" is redundant; however, as with the prion disease, a consistent nomenclature based on the molecular aetiology8 should now be attempted. With this approach, familial early-onset AD with the codon 717 mutation could be designated as P-amyloidopathy (APP717) and hereditary cerebral haemorrhages with amyloidosis Dutch type as P-amyloidopathy (APP693). A simple, rational, and scientifically rigorous classification of this sort would facilitate studies into the underlying biology of these diseases.
ALZHEIMER’S DISEASE RESEARCH GROUP*
*J. Hardy, M. Mullan, M.-C. Chartier-Harlin, J. Brown, A. Goate, M. Rossor, J. Collinge, and G. Roberts (St Mary’s Hospital Medical School, London W2, UK); P. Luthert and P. Lantos (Institute of Psychiatry, London SE5); S. Naruse, K. Kaneko, S. Tsuji, and T. Miyatake (Brain Research Institute, Niigata University, Japan); T. Shimizu (University of Tokyo); T. Kojima (Horinouchi Hospital, Japan); 1. Nakano (Institute of Brain Research, University of Tokyo); K. Yoshioka and Y. Sakaki (Kyushu University, Japan); T. Miki, T. Katsuya, and T. Ogihara (Osaka University Medical School, Japan); A. Roses and M. Pericak-Vance (Duke University Medical Center, Durham, North Carolina, USA); J. Haan and R. Roos (Academic Hospital Leiden, Netherlands); and G. Lucotte and F. Favid (Hopital Robert Dubre, Reims, France). Correspondence to Dr John Hardy, Department of Biochemistry and Molecular Genetics, St Mary’s Hospital Medical School, Norfolk Place, London W2 1PG, UK. 1. Goate AM, Chartier-Harlin MC, Mullan M, et al. Segregation ofa missense mutation m the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 1991; 349: 704-06. 2. Van Broeckhoven C, Haan J, Bakker B, et al. The beta-amyloid precursor protein gene is tightly linked to the locus causing hereditary cerebral haemorrhage with amyloidosis of Dutch type. Science 1990; 248: 1120-23. 3. Levy E, Carman MD, Fernandez-Madrid IJ, et al. Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage with amyloidosis of Dutch type. Science 1990; 248: 1124-26. 4. Haan J, Lanser JBK, Zijderveld I, et al. Dementia in hereditary cerebral haemorrhage with amyloidosis-Dutch type. Arch Neurol 1990; 47: 965-68. 5. St George-Hyslop P, Haines J, Farrar L, et al. Genetic linkage studies suggest that Alzheimer’s disease is not a single homogeneous disorder. Nature 1990; 347: 194-97. 6. Van Duijn C, Hofman A, Kay DWK, eds. Risk factors for Alzheimer’s disease: a collaborative analysis of case control studies. Int J Epidemiol (in press). 7. Collmge J, Owen F, Poulter M, et al. Prion dementia without characteristic pathology. Lancet 1990; 336: 7-9. 8. Roberts GW, Lofthouse R, Allsop D, et al. CNS amyloid proteins in neurodegenerative diseases. Neurology 1988; 38: 1534-40.
Aspirin, warfarin, and
recurrent stroke
SIR,-Since both aspirin and warfarin are associated with an increased risk of cerebral haemorrhage and gastrointestinal bleeding, it would be useful to know whether use of these drugs is justified after a stroke. A full-scale clinical trial to answer this question would be costly and some would argue that more urgent issues should have priority. We have analysed information on use of these drugs and frequency of recurrent stroke collected during a National Institutes of Health sponsored study of recurrent stroke and risk factor control in the Lehigh Valley, USA. 686 patients were enrolled within two weeks of an initial stroke. The stroke was verified clinically and by computerised tomography. Diagnostic criteria similar to those of the Stroke Data Bankl were used to diagnose stroke type and recurrent stroke. Of the 686, 41 had cerebral haemorrhage and aspirin or warfarin would not be indicated. Of the remaining 645, 139 were lost before the first
follow-up visit because of self-withdrawal (33), moving away from the study area (12), death (66), or second stroke (28). Data on the use of aspirin or warfarin were incomplete for these 139 patients. The remaining 506 were evaluated 3-4 months after the stroke and thereafter at about every 6 months until a second stroke, death, or loss to follow-up. At each follow-up visit, patients were asked about use of aspirin (including products containing it) or warfarin. The 506 patients with ischaemic stroke were followed up for an average of 22 (SD 10) months (range 3-43). 122 reported receiving neither aspirin nor warfarin-and 13 (10-7%) of these had a second stroke; of the 232 who had received aspirin only, 18 (7-8%) had a second stroke; among the 109 who had received only warfarin, 8 (7-3%) had a second stroke. 43 had received both drugs and none had a second stroke. Thus, patients on aspirin or warfarin had similar frequencies of stroke recurrence. The combination (sequence not specified) may have been better than either drug alone (3 cases expected, none observed; p 0-06). When the 384 patients treated with aspirin and/or warfarin were compared with those who had neither drug (122), there was no significant difference in frequency of second stroke (6-7% vs 10-7%; p 0-16). Thus, aspirin and/or warfarin does not seem to prevent stroke recurrence when compared with no such treatment. Our analysis was based on data incidentally available from another study. While the treated and untreated groups were similar at enrolment in frequency of hypertension, diabetes, myocardial infarction, atrial fibrillation, and history of transient ischaemic attacks, they differed in several important variables that can affect risk of stroke recurrence. For example, the untreated group had more females, more patients over age 75, and more patients with cardiac arrhythmia other than atrial fibrillation: =
=
Untreated Treated Feature Female
(%))
(%))
57
45
14 24 62
27 39 34
36
30
0.248
37 25 66 18 17
30 23 49 16
0136 0656 0001 0-530 0-807
p 0-013
Age (yr) <65 65-74 75+
Hypertension (> 160 mm Hg systolic; >95 diastolic) Diabetes (> 150 mgdl or on treatment) Myocardial infarction (ECG) Any arrhythmia (ECG) Atrial fibrillation (ECG) Transient ischaemic attack
18
<0-001
Our study does not support the use of aspirin or warfarin to prevent second stroke but a more definitive result could be obtained if sufficient patients were randomly allocated between the two treatments and monitored for compliance. Also, it would be appropriate to look for possible benefits in subgroups with different types of stroke such as embolic stroke. Whether this effort warrants the cost, given our results, is open to question. The Lehigh Valley cohort ROI-NS22188-06-
study was supported by NIH grant, NINDS
Neuroepidemiology Section, Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129,
USA
Department of Preventive Medicine, University of Southern California, Los Angeles, California
MILTON ALTER SUE-MIN LAI GARY H. FRIDAY
EUGENE SOBEL
Lehigh University, Centre for Social Research,
LORI
Bethlehem, Pennsylvania
J. TOEDTER
1. Kunitz SC, Gross CR, Heyman A, et al. The pilot stroke data bank: definition, design, and data. Stroke 1984; 25: 740-46.
Rapid diagnosis of myocardial infarction by immunoturbidimetric myoglobin measurement and early identification of acute myocardial (AMI) in patients with a non-diagnostic electrocardiogram remains an important concern in emergency
SIR,-Rapid
infarction
1344
medicine. In AMI, myoglobin can be detected in plasma soon after onset of chest pain and before a rise in creatine kinase (CK) activity.I However, immunoassays for myoglobin are both time consuming and unsuitable for emergency laboratories. Moreover, the latexagglutination test provides reliable semiquantitative estimations of myoglobin concentrations only when completed by trained assistants under optimum laboratory conditions.2 An immunoturbidimetric myoglobin assay for use with the ’Turbitimer’ (Behring Werke, Marburg, Germany) has been introduced recently.3 This assay gives quantitative results within 1-2 min; plasma myoglobin concentrations are available 10-15 min after blood withdrawal. Plasma from 118 patients with chest pain (43 AMI, 51 angina pectoris, 24 other diseases), who were admitted to the emergency ward of our department of internal medicine within 6 h of onset of symptoms (median 165 min, range 45-360), were assayed for CK activity (Merck, Darmstadt, Germany) and myoglobin. Blood samples were drawn immediately after admission. All patients were free from trauma. A final diagnosis was made according to World Health Organisation criteria for AMI,4 and did not include myoglobin test results. 36% of our sample had a confirmed AMI. Our results suggest that immunoturbidimetric myoglobin measurements have an important role in early diagnosis of AMI: CK activity* p (x2) 0-01 37% 67% 0-23 82% 91% 0-05 55% 81% 0-06 83% 70% 001 82% 66% *Cutoff values of 70 119/1 and 70 U/I were applied for myoglobin and CK, respectively
Myoglobin*
Sensitivity Specificity Positive predictive value Negative predictive value Efficiency
A positive test result must be judged in the light of the clinical setting. In the absence of skeletal muscle damage or impaired renal function, a positive myoglobin test result predicts AMI with a high probability. Myoglobin must be measured soon after a heart attack. If hospital admission is delayed for 12-24 h or more, myoglobin concentrations will have fallen sharply.’ A negative test result in the 4-12 h period after onset of symptoms allows AMI to be ruled out
A group of indigenous people called the Yanomami live in an area straddling the Brazil/Venezuela border. Several years ago gold was discovered under the fragile surface of the Amazon rain-forest. Inorganic mercury is used by miners to extract the gold. Despite efforts to remove the miners, environmental destruction has caused many of the Yanomami to move north into Venezuela. There, at the origin of the Orinoco River, gold-mining using mercury has begun anew, and the river and its basin, the source of water and food (fish, roots) for this population, is now contaminated with this neurotoxin. In 1989, Japanese researchers from the Medical University of Kumamoto took hair samples from Yanomami in BrazilThey found levels in excess of the World Health Organisation allowable exposure limit. Although increased hair levels are not strictly diagnostic of systemic toxicity, they do confirm continuing exposure in this population. Mercury, malaria, and malnutrition form a triad which has killed an estimated 10% of the Yanomami and threatens their very existence.5 The Amazon rain-forest has recently been opened to oil exploration by companies based in the US and in other nations. Increasing poverty and enormous debt in the region put pressure on Bolivia, Ecuador, Peru, Brazil, and Venezuela to allow local and multinational interests to extract minerals and fossil fuels, and to clear forests for the export of lumber and for cattle-all activities that contribute to chemical and infectious diseases, as well as environmental degradation. Mercury poisoning in the Amazon is one consequence of a form of development that is unsustainable. The memory of Minamata (up to 10 000 cases and up to 1000 deaths) must generate bold moves towards prevention. The medical profession can assert its true public health role in the 1990s,6 and join a growing international movement that seeks to regulate and control the genesis of diseases for which there are no cures. Department of Medicine, Harvard Medical School and Cambridge Hospital, Cambridge, Massachusetts 02139, USA
PAUL R. EPSTEIN
within a few minutes. Agocs MM, Etzel RA, Parrish RG, et al. Mercury exposure from interior latex paint. N Engl J Med 1990; 323: 1096-101. 2. CDC. Occurence of mercury poisoning—Nicaragua. MMWR 1980; 29: 393-95. 3. Christrup J. Apartheid and pollution. Greenpeace 1990 (May/June): 18-19 4. Anon. Yanomami. a todos os povos da terra In. Accao pela citizema. Sâo Paulo 1.
J. MAIR J. SMIDT E. ARTNER-DWORZAK Department of Medical Chemistry and Biochemistry,P. LECHLEITNER and Department of Internal Medicine, F. DIENSTL University of Innsbruck, B. PUSCHENDORF A-6020 Innsbruck, Austria. 1. Drexel H, Dworzak E, Kirchmair W, Milz M, Puschendorf B, Dienstl F. Myoglobinemia in the early phase of acute myocardial infarction. Am Heart J 1983; 105: 642-51. 2. Hangaard J, Rasmussen O, Norregaard-Handen K, Jorgensen N, Simmonsen EE, Norgaard-Pedersen B. Early diagnosis of acute myocardial infarction with a rapid latex agglutination test for semi-quantitative estimation of serum myoglobin. Acta Med Scand 1987; 221: 343-48. 3. Tuengler P, Metzmann E, Pauly HE, Becker W. New immunodiagnostic systems. Behring Inst Mitt 1988; 82: 282-308. 4. World Health Organisation criteria for the diagnosis of acute myocardial infarction Proposal for the multinational monitoring of trends and determinants in cardiovascular disease. Geneva. Cardiovascular disease unit of WHO, 1981.
Mercury poisoning SIR,-A recent account of an outbreak of mercury poisoning in the United States1 refers to the sentinel outbreak of Minamata disease in Japan, and mentions incidents in Argentina and Iraq. The list of countries affected by mercury contamination is wider than that. In 1980, the US Centers for Disease Control reported contamination of Lake Nicaragua from the manufacture of batteries.2 Researchers at Greenpeace have documented mercury contamination in Natal Province, South Africa. Sediment levels as high as 1760 parts per million (8800 times the US hazardous waste limit) were found near populated areas downstream from the world’s largest mercury processing factory, which treats waste from pharmaceutical and chemical industries based in the US and elsewhere.We must now include yet another region: sections of the Amazon River basin.
Commission to Create a Yanomami Park, 1991: 37. 5. Dumanoski D. Brazil Indian tribe decimated by illness. Boston Globe Nov 27, 1990: 3. 6. Leaf A. Potential health effects of global climatic and environmental changes. N Engl J Med 1989; 321: 1577-83.
Neonatal extracorporeal membrane
oxygenation SIR,-We disappointed by Dr Elliott’s view (Feb 23, p 476) of neonatal extracorporeal membrane oxygenation (ECMO). We feel that his is a rather glib assessment of the difficulties surrounding the use of controlled trials in life and death situations. Elliott indicates that a large number of infants had received ECMO (3544 by December, 1990) but fails to point out that the current survival rate for term infants (the main group of 3528) was 83%.’ There seems no doubt therefore that ECMO works as a means of short-term cardiorespiratory support. Follow-up data on morbidity indicate no worse an outlook for babies who receive ECMO rather than conventional treatment.2,3 There are data suggesting that ECMO is cost effective.4 It is the head-to-head comparison of ECMO with conventional treatment, which has not been done, that should be the next step in the UK. However, the ethical difficulties should not be underestimated. The use of surfactant treatment as an analogous therapeutic situation is not appropriate since surfactant is a supplement to conventional therapy, not an alternative. The introduction of artificial ventilation for preterm infants is a more appropriate comparison in respect of ethical dilemmas, and no large-scale randomised trial has been done. Few would now be keen to embark on such a trial. We wish to establish a randomised trial of ECMO in the UK before the ethical issue is further blurred by anecdotal were
vascular lesions.2-4 Thus the phenotypes of the
two
mutations
overlap and both include cerebrovascular and brain parenchymal lesions. A very high proportion of patients with dementia have a mixed vascular and Alzheimer pathology. While this may reflect dual pathology it could, in some cases, be part of an extended spectrum of
expression of 0-amyloid disease involving angiopathy. AD is aetiologically heterogeneous5 and genetic factors and head injury are risk factors. This heterogeneity may also contribute to the variation in clinicopathological findings. This story mirrors experience with prion diseases in which the identification of pathogenic mutants led to the realisation that the disease phenotype was very variable.7 Clinical and pathological diagnosis of AD remains important but classification by such means is of limited value. It may be premature to suggest that the term "Alzheimer’s disease" is redundant; however, as with the prion disease, a consistent nomenclature based on the molecular aetiology8 should now be attempted. With this approach, familial early-onset AD with the codon 717 mutation could be designated as P-amyloidopathy (APP717) and hereditary cerebral haemorrhages with amyloidosis Dutch type as P-amyloidopathy (APP693). A simple, rational, and scientifically rigorous classification of this sort would facilitate studies into the underlying biology of these diseases.
ALZHEIMER’S DISEASE RESEARCH GROUP*
*J. Hardy, M. Mullan, M.-C. Chartier-Harlin, J. Brown, A. Goate, M. Rossor, J. Collinge, and G. Roberts (St Mary’s Hospital Medical School, London W2, UK); P. Luthert and P. Lantos (Institute of Psychiatry, London SE5); S. Naruse, K. Kaneko, S. Tsuji, and T. Miyatake (Brain Research Institute, Niigata University, Japan); T. Shimizu (University of Tokyo); T. Kojima (Horinouchi Hospital, Japan); 1. Nakano (Institute of Brain Research, University of Tokyo); K. Yoshioka and Y. Sakaki (Kyushu University, Japan); T. Miki, T. Katsuya, and T. Ogihara (Osaka University Medical School, Japan); A. Roses and M. Pericak-Vance (Duke University Medical Center, Durham, North Carolina, USA); J. Haan and R. Roos (Academic Hospital Leiden, Netherlands); and G. Lucotte and F. Favid (Hopital Robert Dubre, Reims, France). Correspondence to Dr John Hardy, Department of Biochemistry and Molecular Genetics, St Mary’s Hospital Medical School, Norfolk Place, London W2 1PG, UK. 1. Goate AM, Chartier-Harlin MC, Mullan M, et al. Segregation ofa missense mutation m the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 1991; 349: 704-06. 2. Van Broeckhoven C, Haan J, Bakker B, et al. The beta-amyloid precursor protein gene is tightly linked to the locus causing hereditary cerebral haemorrhage with amyloidosis of Dutch type. Science 1990; 248: 1120-23. 3. Levy E, Carman MD, Fernandez-Madrid IJ, et al. Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage with amyloidosis of Dutch type. Science 1990; 248: 1124-26. 4. Haan J, Lanser JBK, Zijderveld I, et al. Dementia in hereditary cerebral haemorrhage with amyloidosis-Dutch type. Arch Neurol 1990; 47: 965-68. 5. St George-Hyslop P, Haines J, Farrar L, et al. Genetic linkage studies suggest that Alzheimer’s disease is not a single homogeneous disorder. Nature 1990; 347: 194-97. 6. Van Duijn C, Hofman A, Kay DWK, eds. Risk factors for Alzheimer’s disease: a collaborative analysis of case control studies. Int J Epidemiol (in press). 7. Collmge J, Owen F, Poulter M, et al. Prion dementia without characteristic pathology. Lancet 1990; 336: 7-9. 8. Roberts GW, Lofthouse R, Allsop D, et al. CNS amyloid proteins in neurodegenerative diseases. Neurology 1988; 38: 1534-40.
Aspirin, warfarin, and
recurrent stroke
SIR,-Since both aspirin and warfarin are associated with an increased risk of cerebral haemorrhage and gastrointestinal bleeding, it would be useful to know whether use of these drugs is justified after a stroke. A full-scale clinical trial to answer this question would be costly and some would argue that more urgent issues should have priority. We have analysed information on use of these drugs and frequency of recurrent stroke collected during a National Institutes of Health sponsored study of recurrent stroke and risk factor control in the Lehigh Valley, USA. 686 patients were enrolled within two weeks of an initial stroke. The stroke was verified clinically and by computerised tomography. Diagnostic criteria similar to those of the Stroke Data Bankl were used to diagnose stroke type and recurrent stroke. Of the 686, 41 had cerebral haemorrhage and aspirin or warfarin would not be indicated. Of the remaining 645, 139 were lost before the first
follow-up visit because of self-withdrawal (33), moving away from the study area (12), death (66), or second stroke (28). Data on the use of aspirin or warfarin were incomplete for these 139 patients. The remaining 506 were evaluated 3-4 months after the stroke and thereafter at about every 6 months until a second stroke, death, or loss to follow-up. At each follow-up visit, patients were asked about use of aspirin (including products containing it) or warfarin. The 506 patients with ischaemic stroke were followed up for an average of 22 (SD 10) months (range 3-43). 122 reported receiving neither aspirin nor warfarin-and 13 (10-7%) of these had a second stroke; of the 232 who had received aspirin only, 18 (7-8%) had a second stroke; among the 109 who had received only warfarin, 8 (7-3%) had a second stroke. 43 had received both drugs and none had a second stroke. Thus, patients on aspirin or warfarin had similar frequencies of stroke recurrence. The combination (sequence not specified) may have been better than either drug alone (3 cases expected, none observed; p 0-06). When the 384 patients treated with aspirin and/or warfarin were compared with those who had neither drug (122), there was no significant difference in frequency of second stroke (6-7% vs 10-7%; p 0-16). Thus, aspirin and/or warfarin does not seem to prevent stroke recurrence when compared with no such treatment. Our analysis was based on data incidentally available from another study. While the treated and untreated groups were similar at enrolment in frequency of hypertension, diabetes, myocardial infarction, atrial fibrillation, and history of transient ischaemic attacks, they differed in several important variables that can affect risk of stroke recurrence. For example, the untreated group had more females, more patients over age 75, and more patients with cardiac arrhythmia other than atrial fibrillation: =
=
Untreated Treated Feature Female
(%))
(%))
57
45
14 24 62
27 39 34
36
30
0.248
37 25 66 18 17
30 23 49 16
0136 0656 0001 0-530 0-807
p 0-013
Age (yr) <65 65-74 75+
Hypertension (> 160 mm Hg systolic; >95 diastolic) Diabetes (> 150 mgdl or on treatment) Myocardial infarction (ECG) Any arrhythmia (ECG) Atrial fibrillation (ECG) Transient ischaemic attack
18
<0-001
Our study does not support the use of aspirin or warfarin to prevent second stroke but a more definitive result could be obtained if sufficient patients were randomly allocated between the two treatments and monitored for compliance. Also, it would be appropriate to look for possible benefits in subgroups with different types of stroke such as embolic stroke. Whether this effort warrants the cost, given our results, is open to question. The Lehigh Valley cohort ROI-NS22188-06-
study was supported by NIH grant, NINDS
Neuroepidemiology Section, Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129,
USA
Department of Preventive Medicine, University of Southern California, Los Angeles, California
MILTON ALTER SUE-MIN LAI GARY H. FRIDAY
EUGENE SOBEL
Lehigh University, Centre for Social Research,
LORI
Bethlehem, Pennsylvania
J. TOEDTER
1. Kunitz SC, Gross CR, Heyman A, et al. The pilot stroke data bank: definition, design, and data. Stroke 1984; 25: 740-46.
Rapid diagnosis of myocardial infarction by immunoturbidimetric myoglobin measurement and early identification of acute myocardial (AMI) in patients with a non-diagnostic electrocardiogram remains an important concern in emergency
SIR,-Rapid
infarction
1344
medicine. In AMI, myoglobin can be detected in plasma soon after onset of chest pain and before a rise in creatine kinase (CK) activity.I However, immunoassays for myoglobin are both time consuming and unsuitable for emergency laboratories. Moreover, the latexagglutination test provides reliable semiquantitative estimations of myoglobin concentrations only when completed by trained assistants under optimum laboratory conditions.2 An immunoturbidimetric myoglobin assay for use with the ’Turbitimer’ (Behring Werke, Marburg, Germany) has been introduced recently.3 This assay gives quantitative results within 1-2 min; plasma myoglobin concentrations are available 10-15 min after blood withdrawal. Plasma from 118 patients with chest pain (43 AMI, 51 angina pectoris, 24 other diseases), who were admitted to the emergency ward of our department of internal medicine within 6 h of onset of symptoms (median 165 min, range 45-360), were assayed for CK activity (Merck, Darmstadt, Germany) and myoglobin. Blood samples were drawn immediately after admission. All patients were free from trauma. A final diagnosis was made according to World Health Organisation criteria for AMI,4 and did not include myoglobin test results. 36% of our sample had a confirmed AMI. Our results suggest that immunoturbidimetric myoglobin measurements have an important role in early diagnosis of AMI: CK activity* p (x2) 0-01 37% 67% 0-23 82% 91% 0-05 55% 81% 0-06 83% 70% 001 82% 66% *Cutoff values of 70 119/1 and 70 U/I were applied for myoglobin and CK, respectively
Myoglobin*
Sensitivity Specificity Positive predictive value Negative predictive value Efficiency
A positive test result must be judged in the light of the clinical setting. In the absence of skeletal muscle damage or impaired renal function, a positive myoglobin test result predicts AMI with a high probability. Myoglobin must be measured soon after a heart attack. If hospital admission is delayed for 12-24 h or more, myoglobin concentrations will have fallen sharply.’ A negative test result in the 4-12 h period after onset of symptoms allows AMI to be ruled out
A group of indigenous people called the Yanomami live in an area straddling the Brazil/Venezuela border. Several years ago gold was discovered under the fragile surface of the Amazon rain-forest. Inorganic mercury is used by miners to extract the gold. Despite efforts to remove the miners, environmental destruction has caused many of the Yanomami to move north into Venezuela. There, at the origin of the Orinoco River, gold-mining using mercury has begun anew, and the river and its basin, the source of water and food (fish, roots) for this population, is now contaminated with this neurotoxin. In 1989, Japanese researchers from the Medical University of Kumamoto took hair samples from Yanomami in BrazilThey found levels in excess of the World Health Organisation allowable exposure limit. Although increased hair levels are not strictly diagnostic of systemic toxicity, they do confirm continuing exposure in this population. Mercury, malaria, and malnutrition form a triad which has killed an estimated 10% of the Yanomami and threatens their very existence.5 The Amazon rain-forest has recently been opened to oil exploration by companies based in the US and in other nations. Increasing poverty and enormous debt in the region put pressure on Bolivia, Ecuador, Peru, Brazil, and Venezuela to allow local and multinational interests to extract minerals and fossil fuels, and to clear forests for the export of lumber and for cattle-all activities that contribute to chemical and infectious diseases, as well as environmental degradation. Mercury poisoning in the Amazon is one consequence of a form of development that is unsustainable. The memory of Minamata (up to 10 000 cases and up to 1000 deaths) must generate bold moves towards prevention. The medical profession can assert its true public health role in the 1990s,6 and join a growing international movement that seeks to regulate and control the genesis of diseases for which there are no cures. Department of Medicine, Harvard Medical School and Cambridge Hospital, Cambridge, Massachusetts 02139, USA
PAUL R. EPSTEIN
within a few minutes. Agocs MM, Etzel RA, Parrish RG, et al. Mercury exposure from interior latex paint. N Engl J Med 1990; 323: 1096-101. 2. CDC. Occurence of mercury poisoning—Nicaragua. MMWR 1980; 29: 393-95. 3. Christrup J. Apartheid and pollution. Greenpeace 1990 (May/June): 18-19 4. Anon. Yanomami. a todos os povos da terra In. Accao pela citizema. Sâo Paulo 1.
J. MAIR J. SMIDT E. ARTNER-DWORZAK Department of Medical Chemistry and Biochemistry,P. LECHLEITNER and Department of Internal Medicine, F. DIENSTL University of Innsbruck, B. PUSCHENDORF A-6020 Innsbruck, Austria. 1. Drexel H, Dworzak E, Kirchmair W, Milz M, Puschendorf B, Dienstl F. Myoglobinemia in the early phase of acute myocardial infarction. Am Heart J 1983; 105: 642-51. 2. Hangaard J, Rasmussen O, Norregaard-Handen K, Jorgensen N, Simmonsen EE, Norgaard-Pedersen B. Early diagnosis of acute myocardial infarction with a rapid latex agglutination test for semi-quantitative estimation of serum myoglobin. Acta Med Scand 1987; 221: 343-48. 3. Tuengler P, Metzmann E, Pauly HE, Becker W. New immunodiagnostic systems. Behring Inst Mitt 1988; 82: 282-308. 4. World Health Organisation criteria for the diagnosis of acute myocardial infarction Proposal for the multinational monitoring of trends and determinants in cardiovascular disease. Geneva. Cardiovascular disease unit of WHO, 1981.
Mercury poisoning SIR,-A recent account of an outbreak of mercury poisoning in the United States1 refers to the sentinel outbreak of Minamata disease in Japan, and mentions incidents in Argentina and Iraq. The list of countries affected by mercury contamination is wider than that. In 1980, the US Centers for Disease Control reported contamination of Lake Nicaragua from the manufacture of batteries.2 Researchers at Greenpeace have documented mercury contamination in Natal Province, South Africa. Sediment levels as high as 1760 parts per million (8800 times the US hazardous waste limit) were found near populated areas downstream from the world’s largest mercury processing factory, which treats waste from pharmaceutical and chemical industries based in the US and elsewhere.We must now include yet another region: sections of the Amazon River basin.
Commission to Create a Yanomami Park, 1991: 37. 5. Dumanoski D. Brazil Indian tribe decimated by illness. Boston Globe Nov 27, 1990: 3. 6. Leaf A. Potential health effects of global climatic and environmental changes. N Engl J Med 1989; 321: 1577-83.
Neonatal extracorporeal membrane
oxygenation SIR,-We disappointed by Dr Elliott’s view (Feb 23, p 476) of neonatal extracorporeal membrane oxygenation (ECMO). We feel that his is a rather glib assessment of the difficulties surrounding the use of controlled trials in life and death situations. Elliott indicates that a large number of infants had received ECMO (3544 by December, 1990) but fails to point out that the current survival rate for term infants (the main group of 3528) was 83%.’ There seems no doubt therefore that ECMO works as a means of short-term cardiorespiratory support. Follow-up data on morbidity indicate no worse an outlook for babies who receive ECMO rather than conventional treatment.2,3 There are data suggesting that ECMO is cost effective.4 It is the head-to-head comparison of ECMO with conventional treatment, which has not been done, that should be the next step in the UK. However, the ethical difficulties should not be underestimated. The use of surfactant treatment as an analogous therapeutic situation is not appropriate since surfactant is a supplement to conventional therapy, not an alternative. The introduction of artificial ventilation for preterm infants is a more appropriate comparison in respect of ethical dilemmas, and no large-scale randomised trial has been done. Few would now be keen to embark on such a trial. We wish to establish a randomised trial of ECMO in the UK before the ethical issue is further blurred by anecdotal were