- Email: [email protected]
HOLTER MONITORING DURING 1981 ATHENS EARTHQUAKES
1281 We studied deaths in pregnancy under four headings: (a) Direct mortality- deaths during pregnancy, labour, or the puerperium due to a direct obstetric cause and not related to any previous maternal illness. (b) Coexistent indirect mortality-deaths due to an additionallllness during pregnancy but unrelated to the pregnancy itself (eg, pneumonia or a cerebrovascular accident). (c) Independent mortalzty-deaths during pregnancy not due to any pathological process (eg, the result of an accident). (d) Pre-existent indirect mortality-deaths due to aggravation by pregnancy of a previous illness (eg, aggravation ofcardiopathy or nephropathy).
Only (d), the pre-existent indirect causes of mortality, are relevant here: where aggravation of an illness by pregnancy might be lifethreatening, interruption of the pregnancy could result in an improvement in the woman’s health. MATERNAL MORTALITY DUE TO PRE-EXISTENT INDIRECT CAUSES
HOLTER MONITORING DURING 1981 ATHENS EARTHQUAKES
SIR,-Professor Trichdpouios and colleagues describe (Feb 26, p 441) an increase in deaths from cardiac events after the major earthquake in Athens on Feb 24, 1981. The increase was significant during the third day after the earthquake and appeared mainly among people with atherosclerotic heart disease. Trichopoulos et al put the blame on psychological stress acting on subjects with a background of atherosclerosis. Malignant rhythm disturbances are suspected as possible trigger mechanisms of death, although direct evidence is lacking. Furthermore the delayed increase in deaths needs interpretation. We have analysed tapes from patients on Holter monitoring at the time of the earthquakes, comparing continuous records during the 10 min before the earthquake with recordings during the first 10 min immediately after the earthquakes and every tenth minute for an
hour after the
event.
ECG DISTURBANCES DURING
Using this classification we looked at maternal deaths in 548 382 pregnancies managed in four large maternity hospitals in Madrid, Barcelona, Valencia, and Bilbao during the period 1971-79. Death rates (per 100 000) were: (a) direct causes, 20-90; (b) coexistent indirect causes, 3 - 48; (d) pre-existent indirect causes, 4 - 39 (see table). Total mortality was 29 - 31 per 100 000, a figure close to that reported by other Western countries. In other words, an indication for therapeutic abortion on the grounds that the mother’s life was endangered by the pregnancy would arise in fewer than 5 pregnancies out
of 100 000.
EARTHQUAKES
The results (table) suggest that disturbances of cardiac rhythm do times of earthquake stress in some people with ischaemic heart disease or pre-existing rhythm disturbances. Furthermore, the fact that repeated earthquakes retriggered rhythm disturbances implies that recurrence of earthquake related stress does not occur at
J. AZNAR J. ESCAMILLA J. GILABERT
Ciudad Sanitaria "La Fe",
Valencia, Spain
LEAD IN PETROL
SIR,-Dr Russell Jones (May 7, p 1042) claims that blood lead levels in Tokyo fell by 70% when lead-free petrol was introduced in Japan. Me cites two unusual studies. Goldwater and HooverlI recorded blood (and urine) lead concentrations in "normal subjects" in fifteen countries. The subjects were males and females in rural and urban areas, and many were hospital employees or clinic patients. No description, not even of sex, is given for the 40 subjects from Japan. We are not told how blood lead was measured or given any data on quality control, but the arithmetic mean blood lead was 20±8 (SD) g/dl. The second study2was based on schoolteachers in ten countries. The aim was to identify about 200 teachers in each country but the sampling procedure and response rates are not provided. The data for Japan are based on 100 male and 100 female teachers who are said to have had an overall geometric mean blood lead level of 60--L 1 -4 (SD) g/1 of blood. This figure happens to be 30% of that reported in the earlier study. It seems remarkable that anyone should judge that these data-from two surveys sixteen years apart, neither of which attempted to study a representative sample of the population in Tokyo-lead to the "obvious conclusion that petrol is the main source of lead in human beings". MRC Epidemiology Unit 4 Richmond Road, Cardiff CF2 3AS
Fig l-ECGs in 46-year-old woman. Upper: immediately before earthquake.
Lower: during
(South Wales),
P.C.ELWOOD
1. Goldwater LJ, Hoover AW. An international study of "normal" levels of lead in blood and urine. Arch Environ Health 1967; 15: 60. 2 Friberg L, Vahter M. Assessment of exposure to lead and cadmium through biological monitoring: Results ofa UNEP/WHO global study. Environ Res 1983; 30: 95.
Fig 2-ECGs in 61-year-old man (as
in
fig 1.)
earthquake.
1282 result in deconditioning and in attenuation of the response. Our findings do support the assumption of Trichopoulos et al that stress due to earthquakes might lead to development of disturbances associated with intense vagal activity (fig 1) or increased sympathetic drive (fig 2).
necessarily
Cardiac
Department,
Evanghelismos Hospital, Athens 140, Greece
E. M. VORIDIS K. D. MALLIOS T. M. PAPANTONIS
deterioration in the doctor-patient relationship and to the patient seeking help elsewhere. Some follow-up studieshave demonstrated that such a deterioration can occur in a substantial number of patients with normal coronary arteries: about 40% continue to pose considerable problems despite having been told that their coronary arteries are normal or near-normal. Departments of Psychological Medicine, Chest Medicine and Cardiology, King’s College Hospital, London SE5 9RS
UNEXPLAINED BREATHLESSNESS AND PSYCHIATRIC MORBIDITY IN PATIENTS WITH NORMAL AND ABNORMAL CORONARY ARTERIES
SIR,-We would like to reply to the comments (April 23, p 931) on March 19 paper. Dr Blackwell and colleagues remark that our
our
patients with normal coronary arteries had increased levels of anxiety because the psychiatric assessment was conducted after angiography, before disclosure of the results. They infer that anxiety levels were falsely raised as a result of stress induced by the procedure. This criticism fails to take into consideration two important facts. Firstly, all 99 patients were assessed blindly at the same stage after angiography: higher levels of psychiatric morbidity were found only in those without significant disease. Secondly, the standardised psychiatric interview yields ratings of each of eleven symptoms experienced during the previous two weeks as well as twelve abnormalities observed at interview. Thus, psychiatric morbidity detected in patients without demonstrable disease cannot be attributed to the trauma of angiography. Blackwell et al also criticise us for not attempting to make alternative diagnoses. However, Heupler et all discounted coronary, artery as a possible cause of chest pain in patients with normal,
CHRISTOPHER BASS W. N. GARDNER GRAHAM JACKSON
CANCER CHEMOTHERAPY ALTERS PLASMA CONCENTRATION OF IMMUNOREACTIVE CALCITONIN
SIR,-Cancer specialists and haematologists are interested in plasma concentrations of immunoreactive calcitonin (ICT) because of their diagnostic value in medullary thyroid carcinoma and because increased plasma ICT values may indicate changes in bronchogenic carcinoma tumour massand progression in myeloid leukaemias.2Vincristine produces an inappropriate secretion of antidiuretic hormone and abnormalities of gastrointestinal endocrine tissue.3 However, a direct influence of chemotherapy on plasma concentrations of ICT has not been reported. We have measured plasma ICT levels in before and 2 days after the start of multidrug chemotherapy which included vincristine. Patients with Hodgkin’s disease (3), acute lymphoblastic leukaemia (2), multiple myeloma (2), non-Hodgkin’s lymphoma (I), acute myeloid leukaemia (1), and breast carcinoma (1) were studied immediately before and 48 h after chemotherapy. No patient had hypercalcaemia or renal failure. All patients received vincristine, and most weregiven other agents, including prednisone,
melphalan, nitrogen mustard, procarbazine, cyclophosphamide,
coronary arteries. We are aware of the work of Alban Davies et al,2 who demonstrated that oesophageal disorders can produce symptoms that mimic cardiac ischaemia. However, we pointed out that barium and/or endoscopies were done in 20 (43%) of the patients without demonstrable disease, and abnormalities were detected in only 4. Only 1 of these patients was subsequently relieved of chest pain following treatment. It seems likely that gastro-oesophageal disorders accounted for the chest pain in only a small proportion of our patients. We have no experience of manipulation of the costovertebral joints in patients with chest wall pain. Dr Eastwood claims that this procedure is "immediately curative" in his hands. Our study made no claims for treatment. However, we did find an association between chest wall tenderness and unexplained breathlessness, and all but a quarter of this group of patients had conspicuous
and doxorubicin. All patients gave informed consent, and permission to carry out this study was obtained from the ethical committee of the Queen’s University of Beffast. Blood samples were collected into cold heparinised tubes. Plasma was separated immediately, frozen, and stored at -20°C. For radioimmunoassay were used antisera to synthetic human calcitonin kindly supplied by Armour Pharmaceutical (batch K692-229-2) and Medical Research Council human calcitonin standard. Assay methodology was similar to that described for gastrin.4 The limit of detection of calcitonin was 15 ng/l (3’75 pmol/1). All but 1 patient had higher levels of circulating ICT 48 h after chemotherapy than before, means ±SEM being 131±37 ng/ml (range 10-390) before and 282±97 ng/ml (range 20-1000) after
psychiatric morbidity.
ICT measurement is thought to be useful in indicating therapeutic responsel or recurrence.2,5 Our studies show that plasma ICT concentrations will often rise within 48 h of the start of chemotherapy, implying that raised plasma ICT levels in patients with malignant disease undergoing combination chemotherapy should be interpreted with caution.
We have been unable to demonstrate a relationship between hypocapnia and the reporting of chest pain in these patients. However, we do not dispute that the pain is musculoskeletal: as long ago as 1945 Friedman3demonstrated that immobilisation of the upper chest with strapping abolished the pain in a similar group of patients with exaggerated thoracic breathing. We are surprised by Eastwood’s implication that the doctorpatient relationship is adversely affected when patients with "unexplained" somatic symptoms are assigned a psychiatric diagnosis. It is now established that about one-third of all patients attending specialist medical clinics with somatic complaints have psychiatric morbidity but no ascertainable organic disorder. 4,5 "Discounting" complaints made by these patients rarely serves their best interests: indeed, such an approach is more likely to lead to
therapy.
C. F. J. is supported Research Fund.
Departments of Medicine and Haematology, Queen’s University of Belfast, Belfast BT12 6BJ
1.
1978; 41: 631-40. Alban Davies H, Jones DB, Rhodes J "Esophageal angina" JAMA 1982; 248: 2274-78
the cause of chest pain.
2.
aetiology and pathogenesis of neurocirculatory asthenia The respiratory manifestation of neurocirculatory asthenia. Am Heart J 1945; 30: 557. 4 Goldberg D. A psychiatric study of patients with diseases of the small intestine Gut 1970; 11: 459-65. 5. Macdonald AJ, Bouchier IAD. Non-organic gastro-intestinal illness: a medical and psychiatric study Br J Psychiatary 1980; 136: 276-83.
3.
2.
3. Friedman M Studies concerning the
as
4.
5
a
grant from the Northern Ireland Leukaemia
C. F. JOHNSTON Z. R. DESAI J. E. S. ARDILL J. M. BRIDGES K. D. BUCHANAN
JM, Salem DN, Banas JS, Levine HJ Long-term clinical course of patients with normal coronary arteriography: Follow-up study of 121 patients with normal or near-normal coronary arteriograms. Am Heart J 1981, 102: 645-53 Mulder H, Hackeng WHL, Silberbusch J, den Ottolander GJH, van der Meer C Value of serum calcitonin estimation in clinical oncology. Br J Cancer 1981. 43: 786-92 Hillyard CJ, Oscier DG, Foa R, Catovsky D, Goldman JM Immunoreactive calcitonine in leukaemia. Br Med J 1979; ii. 1392-93. Johnston CF, Buchanan KD. Vincristine-induced abnormalities of gastrointestinal endocrine tissue in rats. Regul Peptides 1982; 4: 368. Ardill JES Radioimmunoassay of gastrointestinal hormones In Buchanan KD ed Clinics in endocrinology and metabolism: Vol VIII London. W B Saunders. 1979: 265-80 Austin LA, Heath H. Calcitonin: Physiology and pathophysiology N Engl J. Med 1981. 304: 269-78
6. Isner
Heupler FA, Proudfit WL, Razavi M, Shirley EK, Greenstreet R, Sheldon WC. Ergonovine maleate provocation test for coronary arterial spasm. Am J Cardiol
1.
by
Only (d), the pre-existent indirect causes of mortality, are relevant here: where aggravation of an illness by pregnancy might be lifethreatening, interruption of the pregnancy could result in an improvement in the woman’s health. MATERNAL MORTALITY DUE TO PRE-EXISTENT INDIRECT CAUSES
HOLTER MONITORING DURING 1981 ATHENS EARTHQUAKES
SIR,-Professor Trichdpouios and colleagues describe (Feb 26, p 441) an increase in deaths from cardiac events after the major earthquake in Athens on Feb 24, 1981. The increase was significant during the third day after the earthquake and appeared mainly among people with atherosclerotic heart disease. Trichopoulos et al put the blame on psychological stress acting on subjects with a background of atherosclerosis. Malignant rhythm disturbances are suspected as possible trigger mechanisms of death, although direct evidence is lacking. Furthermore the delayed increase in deaths needs interpretation. We have analysed tapes from patients on Holter monitoring at the time of the earthquakes, comparing continuous records during the 10 min before the earthquake with recordings during the first 10 min immediately after the earthquakes and every tenth minute for an
hour after the
event.
ECG DISTURBANCES DURING
Using this classification we looked at maternal deaths in 548 382 pregnancies managed in four large maternity hospitals in Madrid, Barcelona, Valencia, and Bilbao during the period 1971-79. Death rates (per 100 000) were: (a) direct causes, 20-90; (b) coexistent indirect causes, 3 - 48; (d) pre-existent indirect causes, 4 - 39 (see table). Total mortality was 29 - 31 per 100 000, a figure close to that reported by other Western countries. In other words, an indication for therapeutic abortion on the grounds that the mother’s life was endangered by the pregnancy would arise in fewer than 5 pregnancies out
of 100 000.
EARTHQUAKES
The results (table) suggest that disturbances of cardiac rhythm do times of earthquake stress in some people with ischaemic heart disease or pre-existing rhythm disturbances. Furthermore, the fact that repeated earthquakes retriggered rhythm disturbances implies that recurrence of earthquake related stress does not occur at
J. AZNAR J. ESCAMILLA J. GILABERT
Ciudad Sanitaria "La Fe",
Valencia, Spain
LEAD IN PETROL
SIR,-Dr Russell Jones (May 7, p 1042) claims that blood lead levels in Tokyo fell by 70% when lead-free petrol was introduced in Japan. Me cites two unusual studies. Goldwater and HooverlI recorded blood (and urine) lead concentrations in "normal subjects" in fifteen countries. The subjects were males and females in rural and urban areas, and many were hospital employees or clinic patients. No description, not even of sex, is given for the 40 subjects from Japan. We are not told how blood lead was measured or given any data on quality control, but the arithmetic mean blood lead was 20±8 (SD) g/dl. The second study2was based on schoolteachers in ten countries. The aim was to identify about 200 teachers in each country but the sampling procedure and response rates are not provided. The data for Japan are based on 100 male and 100 female teachers who are said to have had an overall geometric mean blood lead level of 60--L 1 -4 (SD) g/1 of blood. This figure happens to be 30% of that reported in the earlier study. It seems remarkable that anyone should judge that these data-from two surveys sixteen years apart, neither of which attempted to study a representative sample of the population in Tokyo-lead to the "obvious conclusion that petrol is the main source of lead in human beings". MRC Epidemiology Unit 4 Richmond Road, Cardiff CF2 3AS
Fig l-ECGs in 46-year-old woman. Upper: immediately before earthquake.
Lower: during
(South Wales),
P.C.ELWOOD
1. Goldwater LJ, Hoover AW. An international study of "normal" levels of lead in blood and urine. Arch Environ Health 1967; 15: 60. 2 Friberg L, Vahter M. Assessment of exposure to lead and cadmium through biological monitoring: Results ofa UNEP/WHO global study. Environ Res 1983; 30: 95.
Fig 2-ECGs in 61-year-old man (as
in
fig 1.)
earthquake.
1282 result in deconditioning and in attenuation of the response. Our findings do support the assumption of Trichopoulos et al that stress due to earthquakes might lead to development of disturbances associated with intense vagal activity (fig 1) or increased sympathetic drive (fig 2).
necessarily
Cardiac
Department,
Evanghelismos Hospital, Athens 140, Greece
E. M. VORIDIS K. D. MALLIOS T. M. PAPANTONIS
deterioration in the doctor-patient relationship and to the patient seeking help elsewhere. Some follow-up studieshave demonstrated that such a deterioration can occur in a substantial number of patients with normal coronary arteries: about 40% continue to pose considerable problems despite having been told that their coronary arteries are normal or near-normal. Departments of Psychological Medicine, Chest Medicine and Cardiology, King’s College Hospital, London SE5 9RS
UNEXPLAINED BREATHLESSNESS AND PSYCHIATRIC MORBIDITY IN PATIENTS WITH NORMAL AND ABNORMAL CORONARY ARTERIES
SIR,-We would like to reply to the comments (April 23, p 931) on March 19 paper. Dr Blackwell and colleagues remark that our
our
patients with normal coronary arteries had increased levels of anxiety because the psychiatric assessment was conducted after angiography, before disclosure of the results. They infer that anxiety levels were falsely raised as a result of stress induced by the procedure. This criticism fails to take into consideration two important facts. Firstly, all 99 patients were assessed blindly at the same stage after angiography: higher levels of psychiatric morbidity were found only in those without significant disease. Secondly, the standardised psychiatric interview yields ratings of each of eleven symptoms experienced during the previous two weeks as well as twelve abnormalities observed at interview. Thus, psychiatric morbidity detected in patients without demonstrable disease cannot be attributed to the trauma of angiography. Blackwell et al also criticise us for not attempting to make alternative diagnoses. However, Heupler et all discounted coronary, artery as a possible cause of chest pain in patients with normal,
CHRISTOPHER BASS W. N. GARDNER GRAHAM JACKSON
CANCER CHEMOTHERAPY ALTERS PLASMA CONCENTRATION OF IMMUNOREACTIVE CALCITONIN
SIR,-Cancer specialists and haematologists are interested in plasma concentrations of immunoreactive calcitonin (ICT) because of their diagnostic value in medullary thyroid carcinoma and because increased plasma ICT values may indicate changes in bronchogenic carcinoma tumour massand progression in myeloid leukaemias.2Vincristine produces an inappropriate secretion of antidiuretic hormone and abnormalities of gastrointestinal endocrine tissue.3 However, a direct influence of chemotherapy on plasma concentrations of ICT has not been reported. We have measured plasma ICT levels in before and 2 days after the start of multidrug chemotherapy which included vincristine. Patients with Hodgkin’s disease (3), acute lymphoblastic leukaemia (2), multiple myeloma (2), non-Hodgkin’s lymphoma (I), acute myeloid leukaemia (1), and breast carcinoma (1) were studied immediately before and 48 h after chemotherapy. No patient had hypercalcaemia or renal failure. All patients received vincristine, and most weregiven other agents, including prednisone,
melphalan, nitrogen mustard, procarbazine, cyclophosphamide,
coronary arteries. We are aware of the work of Alban Davies et al,2 who demonstrated that oesophageal disorders can produce symptoms that mimic cardiac ischaemia. However, we pointed out that barium and/or endoscopies were done in 20 (43%) of the patients without demonstrable disease, and abnormalities were detected in only 4. Only 1 of these patients was subsequently relieved of chest pain following treatment. It seems likely that gastro-oesophageal disorders accounted for the chest pain in only a small proportion of our patients. We have no experience of manipulation of the costovertebral joints in patients with chest wall pain. Dr Eastwood claims that this procedure is "immediately curative" in his hands. Our study made no claims for treatment. However, we did find an association between chest wall tenderness and unexplained breathlessness, and all but a quarter of this group of patients had conspicuous
and doxorubicin. All patients gave informed consent, and permission to carry out this study was obtained from the ethical committee of the Queen’s University of Beffast. Blood samples were collected into cold heparinised tubes. Plasma was separated immediately, frozen, and stored at -20°C. For radioimmunoassay were used antisera to synthetic human calcitonin kindly supplied by Armour Pharmaceutical (batch K692-229-2) and Medical Research Council human calcitonin standard. Assay methodology was similar to that described for gastrin.4 The limit of detection of calcitonin was 15 ng/l (3’75 pmol/1). All but 1 patient had higher levels of circulating ICT 48 h after chemotherapy than before, means ±SEM being 131±37 ng/ml (range 10-390) before and 282±97 ng/ml (range 20-1000) after
psychiatric morbidity.
ICT measurement is thought to be useful in indicating therapeutic responsel or recurrence.2,5 Our studies show that plasma ICT concentrations will often rise within 48 h of the start of chemotherapy, implying that raised plasma ICT levels in patients with malignant disease undergoing combination chemotherapy should be interpreted with caution.
We have been unable to demonstrate a relationship between hypocapnia and the reporting of chest pain in these patients. However, we do not dispute that the pain is musculoskeletal: as long ago as 1945 Friedman3demonstrated that immobilisation of the upper chest with strapping abolished the pain in a similar group of patients with exaggerated thoracic breathing. We are surprised by Eastwood’s implication that the doctorpatient relationship is adversely affected when patients with "unexplained" somatic symptoms are assigned a psychiatric diagnosis. It is now established that about one-third of all patients attending specialist medical clinics with somatic complaints have psychiatric morbidity but no ascertainable organic disorder. 4,5 "Discounting" complaints made by these patients rarely serves their best interests: indeed, such an approach is more likely to lead to
therapy.
C. F. J. is supported Research Fund.
Departments of Medicine and Haematology, Queen’s University of Belfast, Belfast BT12 6BJ
1.
1978; 41: 631-40. Alban Davies H, Jones DB, Rhodes J "Esophageal angina" JAMA 1982; 248: 2274-78
the cause of chest pain.
2.
aetiology and pathogenesis of neurocirculatory asthenia The respiratory manifestation of neurocirculatory asthenia. Am Heart J 1945; 30: 557. 4 Goldberg D. A psychiatric study of patients with diseases of the small intestine Gut 1970; 11: 459-65. 5. Macdonald AJ, Bouchier IAD. Non-organic gastro-intestinal illness: a medical and psychiatric study Br J Psychiatary 1980; 136: 276-83.
3.
2.
3. Friedman M Studies concerning the
as
4.
5
a
grant from the Northern Ireland Leukaemia
C. F. JOHNSTON Z. R. DESAI J. E. S. ARDILL J. M. BRIDGES K. D. BUCHANAN
JM, Salem DN, Banas JS, Levine HJ Long-term clinical course of patients with normal coronary arteriography: Follow-up study of 121 patients with normal or near-normal coronary arteriograms. Am Heart J 1981, 102: 645-53 Mulder H, Hackeng WHL, Silberbusch J, den Ottolander GJH, van der Meer C Value of serum calcitonin estimation in clinical oncology. Br J Cancer 1981. 43: 786-92 Hillyard CJ, Oscier DG, Foa R, Catovsky D, Goldman JM Immunoreactive calcitonine in leukaemia. Br Med J 1979; ii. 1392-93. Johnston CF, Buchanan KD. Vincristine-induced abnormalities of gastrointestinal endocrine tissue in rats. Regul Peptides 1982; 4: 368. Ardill JES Radioimmunoassay of gastrointestinal hormones In Buchanan KD ed Clinics in endocrinology and metabolism: Vol VIII London. W B Saunders. 1979: 265-80 Austin LA, Heath H. Calcitonin: Physiology and pathophysiology N Engl J. Med 1981. 304: 269-78
6. Isner
Heupler FA, Proudfit WL, Razavi M, Shirley EK, Greenstreet R, Sheldon WC. Ergonovine maleate provocation test for coronary arterial spasm. Am J Cardiol
1.
by