- Email: [email protected]
RISK OF ECTOPIC PREGNANCY
1247 drome, kyphoscoliosis, spina bifida, and intrathoracic
We thank Prof. H.
Kemp,
and Dr M. C. Kaiser for their
RISK OF ECTOPIC PREGNANCY
neur-
omas may be part of the clinical picture. Our patient had a rare combination of neurofibroma in the proximal cervical region and diffuse spinal canal stenosis. Double contrast myelography and CT scanning were needed to bring out the association of the two conditions. Both examinations determined the site of the lesion precisely, but CT scanning also demonstrate a defect in the foramen magnum caused by pressure from the neurofibroma and excluded supratentorial manifestations. Cervical myelography with single (metrizamide) or double contrast (air and metrizamide) is easier, more comfortable for the patient and less risky when done via lateral puncture at C2/C3 than when done by the suboccipital route. This is now our usual technique for cervical myelography. CT scanning of the cervical spine with or without intrathecal metrizamide is now a major method of diagnosis of spinal nd neurocanal lesions; furthermore it can, as here, show whether the lesion has extended beyond the neurocanal.
SIR,-Professor Vessey and his colleagues (Sept. 8, p. 501) reported on the risk of ectopic pregnancy in women using an intrauterine device (IUD) and its relation to duration of IUD use. We noted1 that the incidence of ectopic pregnancy had increased in England and Wales since the late 1950s-particularly since 1970-and suggested that part of the increase might have been related to the increasing prevalence of IUD use. At that time information up to 1972 was available, but we now have Hospital In-patient Enquiry (HIPE)2 data up to 1976. The
accompanying
table shows the estimated numbers
ESTIMATED TOTAL HOSPITAL DISCHARGES DUE TO ECTOPIC PREGNANCY BY AGE: ENGLAND AND
WALES, 1966-76*
helpful
criticism, Dr R. de Graaf for his help with the myelography, Ms H. J. Vis and Miss Rowena H. Veiga-Pires for their help in the preparation of this letter and Mr I. de Groot for the illustrations. Departments of Neurology and Radiology, Academisch Ziekenhuis, Utrecht, Netherlands
P. VANCOILLIE J. A. VEIGA-PIRES
FATAL ASTHMA
SIR,-Dr Herxheimer (Nov. 17, p. 1084) says: "Isoprenaline cannot be an important cause [of fatal asthma] because it has been replaced worldwide by other aerosols with different properties, but asthma mortality does not seem to have declined". ASTHMA DEATHS PER
100 000
AND
PERSONS AGED
5-34:
ENGLAND
WALES,1959-78
*Column i=estimated number of hospital discharges due to ectopic pregnancy; column ii=estimated hospital discharge rate per 100 000 women; column iii=estimated ratio of ectopic pregnancies per 1000 conceptions (i.e., per 1000 therapeutic abortions plus births six months
later). of
hospital discharges attributed to ectopic pregnancy (ICD 631, excluding 631-0 and 631.4) for the years 1966 to 1976, the annual age specific hospital discharge rates per 100 000 women, and the estimated proportion of fertilised ova implanting into ectopic sites, expressed as a ratio per 1000 conceptions. Data on legal abortions3 and births4 were used to estimate conceptions, the denominator being the total number of legal abortions performed during that year plus the total births occurring six months later. The ratios are slightly different
Source: O.P.C.S.
Among persons aged 5-34 years in England and Wales asthma mortality per 100 000 per year increased from 0-74 in 1959-61 to a peak 2.18 in 1966.1,2 Thereafter, following a general alert and a warning on aerosol canisters, mortality quickly declined to its level in 1959-61 where it had stood, more or less, for over a hundred years (see table). Mortality has remained below its 1959-61 level since about 1973, so it is not clear why Herxheimer thinks it ought to have declined after isoprenaline was replaced. Abuse of isoprenaline, which was implicated, presumably stopped after the warning in 1967, before isoprenaline was withdrawn. Medical Statistics Division, Office of Population, Censuses and Surveys, London WC2B 6JP 1.
Speizer FE, Doll R. A century of J 1968; iii: 245-46.
from those reported in our earlier paper,’ as these figures have been adjusted for the sampling fraction of HIPE data. The most recent data reveal that, although there are irregularities, the hospital discharge rates for ectopic pregnancy have remained high since 1970. An exception may be at ages 35-44 years where rates have fallen since 1974 but more data are required before this trend can be assessed. When ectopic pregnancies are expressed as a ratio of all estimated conceptions these ratios have generally continued to increase throughout the 1970s. The all-ages ratio has increased from 3.2 per 1000 estimated conceptions in 1966 to 5 -0 in 1976. Erkkola and Liukko noted a similar trend in Turku, Finland.s They found that the increase in ectopic pregnancy incidence could be accounted for largely by the increasing number of ectopics associated with an in situ IUD: from 1966 to 1970, epidemiological study of recent trends in ectopic pregnancy. Br J Obstet Gynæcol 1975; 82: 775-82. 2. Office of Population Censuses and Surveys. Reports of Hospital-In-patient Enquiry. HM Stationery Office. 3. Registrar General’s Statistical Review of England and Wales (1968-1976): supplement on abortion. HM Stationery Office. 4. Registrar General’s Statistical Review of England and Wales (1966-1976). HM Stationery Office. 5. Erkkola R. Liukko P. Intrauterine device and ectopic pregnancy. Contracep1. Beral V. An
A. M. ADELSTEIN
asthma deaths in young
people.
2. Inman WHW, Adelstein AM. Rise and fall of asthma mortality in and Wales in relation to use of pressurised aerosols. Lancet 279-85.
Br Med
England 1969; ii:
tion
1977; 16: 569-74.
1248
2% of ectopic pregnancies were associated with IUD use, whereas from 1971 to 1975, 39% were. Their data also suggest that there may have been an additional small increase in ectopics which were not related to IUD use. Although no direct data are available for Britain, there is some evidence that a similar situation may exist here. Jonas reported that 14% (14 out of 103) of ectopic pregnancy admissions to Hillingdon Hospital between 1967 and 1974 were associated with an in situ IUD,6 as were 14% (3 out of 21) of deaths from ectopic pregnancy in England and Wales between 1973 and 1976.7 If since 1967 14% of hospital admissions for ectopic pregnancy were IUD-related, an annual average of about 450 ectopics in England and Wales would be associated with an in situ device. As in Finland, these 450 ectopic pregnancies would account for much but not all of the increase in ectopic pregnancy incidence. We
acknowledge
the
use
of unpublished data from O.P.C.S.
Epidemiological Monitoring Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT
NICOLA ROBINSON VALERIE BERAL
COLD-PRESSOR TEST
SIR,-Dr Watson and Professor Littler (Oct. 13, p. 803) the
are
of
measuring the haemodyright emphasise namic response to peripheral cold stimulation when using this test with gated cardiac blood pool scintigraphy in the detection of coronary heart disease (Aug. 18, p. 320). All our subjects had a significant increase in heart rate and mean blood pressure (ratexpressure product), and the responses in patients with coronary artery disease (CAD) or cardiomyopathy were similar to those in controls. The figure shows the comparative to
importance
reported to the British Cardiac Society last month) that, in patients undergoing gated blood pool imaging, cold stimulation detected significantly more CAD patients (41/48, 85%) than did isometric exercise (15/24, 62%) or dynamic exercise (13/21, 62%) (p<0.05), a finding which seems to belittle the magnitude of the hxmodynamic response. Every intervention increased the ratexpressure product, a useful measure of myocardial oxygen demand,but it was possible that cold stimulation in addition caused a reduction of myocardial oxygen supply due to spasm of the coronary resistance vessels in patients with CAD. Support for this hypothesis is provided by Mudge et al .2 who have demonstrated increased coronary vascular resistance during the cold pressor test in patients with CAD but not in normal subjects. Moreover, in our study the degree of impairment of left ventricular ejection fraction (LVEF) in response to cold stimulation did not bear a simple relationship to the magnitude of the haemodynamic response but was principally determined by the severity and extent of CAD; patients with triple-vessel disease had the most profound fall in LVEF, usually greater than 15%. We have also seen episodes of transient bradycardia in 3 patients who had significant increases in systemic blood-pressure in response to the cold stimulation; the ratexpressure product was increased in all cases. Unlike Watson and Littler’s patients, none of ours had hypertension, but lately we have studied 4 hypertensive individuals on no therapy; all had excellent, indeed exaggerated, increases of systemic blood-pressure without bradycardia. We would emphasise that alpha and beta blocking drugs were withdrawn from all our patients; these drugs inhibit the cardiovascular response to cold stimulation. Watson and Littler do not say whether such drugs were withdrawn in their cases, but therapy must be considered when a disappointing response to peripheral cold stimulation is encountered. We conclude that the cold pressor test, despite evoking a smaller increment in ratexpressure product, is not only a simpler intervention but also is more sensitive than dynamic or isometric exercise in the detection of patients with ischxmic heart-disease by gated blood pool scintigraphy. Departments of Cardiology and Nuclear Medicine,
Guy’s Hospital, London SE1 9RT
R. J. WAINWRIGHT D. A. BRENNAND-ROPER M. N. MAISEY E. SOWTON
LYMPHOCYTOTOXIC ANTIBODIES IN HYDRALAZINE-INDUCED LUPUS ERYTHEMATOSUS
responses caused by cold stimulation and cise in CAD patients and controls.
Haemodynamie
exer-
response caused by cold stimulation and different forms of exercise in an extended series of 48 CAD patients and 40 controls. Although there was no difference in the ratexpressure product between controls and patients with CAD during any intervention, it was clear that the load imposed upon the heart was far greater with dynamic exercise (supine or upright) than with isometric exercise or cold stimulation. We were, therefore, surprised to find (in a study
haemodynamic
6. Jonas G. Ectopic pregnancy despite intrauterine contraception: A clue to mode of action of IUCD’s. Br Med J 1975; iii: 467. 7. Department of Health and Social Security. Report on confidential enquiries into maternal deaths in
Office.
England
and Wales. 1973-1975. HM
Stationery
SIR,-Dr Bluestein and colleagues (Oct. 20, p. 816) describe cold-reactive lymphocytotoxic antibodies (LCA) in patients with procainamide-induced lupus. LCA titres were closely related to the severity of the disease, unlike antinuclear antibody titres (ANA). Bluestein et al. propose that LCA, resulting from the expression of new drug-induced antigenic determinants, are an important mechanism in the persistence of drug-induced alteration of central immune regulation. During a prospective study of hydralazine in hypertension we had the opportunity to study seven patients with classical hydralazineinduced lupus erythematosus. We compared the ANA titres, LCA indices, and acetylator phenotypes of these patients with those of forty symptom-free patients on hydralazine in whom a positive ANA had developed. All seven patients had severe arthralgia; four had florid synovitis and one had facial erythema. The ESR was above 30 1. Gobel FL, Nordstrom LA, Nelson RR, Jorgenson CR, Wang Y. The ratepressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 1978; 57: 549-56. 2. Mudge GH, Goldberg S, Gunther S, Mann T, Crossman W. Comparison of metabolic and vasoconstrictor stimuli on coronary vascular resistance in man. Circulation 1979; 59: 544-50.
We thank Prof. H.
Kemp,
and Dr M. C. Kaiser for their
RISK OF ECTOPIC PREGNANCY
neur-
omas may be part of the clinical picture. Our patient had a rare combination of neurofibroma in the proximal cervical region and diffuse spinal canal stenosis. Double contrast myelography and CT scanning were needed to bring out the association of the two conditions. Both examinations determined the site of the lesion precisely, but CT scanning also demonstrate a defect in the foramen magnum caused by pressure from the neurofibroma and excluded supratentorial manifestations. Cervical myelography with single (metrizamide) or double contrast (air and metrizamide) is easier, more comfortable for the patient and less risky when done via lateral puncture at C2/C3 than when done by the suboccipital route. This is now our usual technique for cervical myelography. CT scanning of the cervical spine with or without intrathecal metrizamide is now a major method of diagnosis of spinal nd neurocanal lesions; furthermore it can, as here, show whether the lesion has extended beyond the neurocanal.
SIR,-Professor Vessey and his colleagues (Sept. 8, p. 501) reported on the risk of ectopic pregnancy in women using an intrauterine device (IUD) and its relation to duration of IUD use. We noted1 that the incidence of ectopic pregnancy had increased in England and Wales since the late 1950s-particularly since 1970-and suggested that part of the increase might have been related to the increasing prevalence of IUD use. At that time information up to 1972 was available, but we now have Hospital In-patient Enquiry (HIPE)2 data up to 1976. The
accompanying
table shows the estimated numbers
ESTIMATED TOTAL HOSPITAL DISCHARGES DUE TO ECTOPIC PREGNANCY BY AGE: ENGLAND AND
WALES, 1966-76*
helpful
criticism, Dr R. de Graaf for his help with the myelography, Ms H. J. Vis and Miss Rowena H. Veiga-Pires for their help in the preparation of this letter and Mr I. de Groot for the illustrations. Departments of Neurology and Radiology, Academisch Ziekenhuis, Utrecht, Netherlands
P. VANCOILLIE J. A. VEIGA-PIRES
FATAL ASTHMA
SIR,-Dr Herxheimer (Nov. 17, p. 1084) says: "Isoprenaline cannot be an important cause [of fatal asthma] because it has been replaced worldwide by other aerosols with different properties, but asthma mortality does not seem to have declined". ASTHMA DEATHS PER
100 000
AND
PERSONS AGED
5-34:
ENGLAND
WALES,1959-78
*Column i=estimated number of hospital discharges due to ectopic pregnancy; column ii=estimated hospital discharge rate per 100 000 women; column iii=estimated ratio of ectopic pregnancies per 1000 conceptions (i.e., per 1000 therapeutic abortions plus births six months
later). of
hospital discharges attributed to ectopic pregnancy (ICD 631, excluding 631-0 and 631.4) for the years 1966 to 1976, the annual age specific hospital discharge rates per 100 000 women, and the estimated proportion of fertilised ova implanting into ectopic sites, expressed as a ratio per 1000 conceptions. Data on legal abortions3 and births4 were used to estimate conceptions, the denominator being the total number of legal abortions performed during that year plus the total births occurring six months later. The ratios are slightly different
Source: O.P.C.S.
Among persons aged 5-34 years in England and Wales asthma mortality per 100 000 per year increased from 0-74 in 1959-61 to a peak 2.18 in 1966.1,2 Thereafter, following a general alert and a warning on aerosol canisters, mortality quickly declined to its level in 1959-61 where it had stood, more or less, for over a hundred years (see table). Mortality has remained below its 1959-61 level since about 1973, so it is not clear why Herxheimer thinks it ought to have declined after isoprenaline was replaced. Abuse of isoprenaline, which was implicated, presumably stopped after the warning in 1967, before isoprenaline was withdrawn. Medical Statistics Division, Office of Population, Censuses and Surveys, London WC2B 6JP 1.
Speizer FE, Doll R. A century of J 1968; iii: 245-46.
from those reported in our earlier paper,’ as these figures have been adjusted for the sampling fraction of HIPE data. The most recent data reveal that, although there are irregularities, the hospital discharge rates for ectopic pregnancy have remained high since 1970. An exception may be at ages 35-44 years where rates have fallen since 1974 but more data are required before this trend can be assessed. When ectopic pregnancies are expressed as a ratio of all estimated conceptions these ratios have generally continued to increase throughout the 1970s. The all-ages ratio has increased from 3.2 per 1000 estimated conceptions in 1966 to 5 -0 in 1976. Erkkola and Liukko noted a similar trend in Turku, Finland.s They found that the increase in ectopic pregnancy incidence could be accounted for largely by the increasing number of ectopics associated with an in situ IUD: from 1966 to 1970, epidemiological study of recent trends in ectopic pregnancy. Br J Obstet Gynæcol 1975; 82: 775-82. 2. Office of Population Censuses and Surveys. Reports of Hospital-In-patient Enquiry. HM Stationery Office. 3. Registrar General’s Statistical Review of England and Wales (1968-1976): supplement on abortion. HM Stationery Office. 4. Registrar General’s Statistical Review of England and Wales (1966-1976). HM Stationery Office. 5. Erkkola R. Liukko P. Intrauterine device and ectopic pregnancy. Contracep1. Beral V. An
A. M. ADELSTEIN
asthma deaths in young
people.
2. Inman WHW, Adelstein AM. Rise and fall of asthma mortality in and Wales in relation to use of pressurised aerosols. Lancet 279-85.
Br Med
England 1969; ii:
tion
1977; 16: 569-74.
1248
2% of ectopic pregnancies were associated with IUD use, whereas from 1971 to 1975, 39% were. Their data also suggest that there may have been an additional small increase in ectopics which were not related to IUD use. Although no direct data are available for Britain, there is some evidence that a similar situation may exist here. Jonas reported that 14% (14 out of 103) of ectopic pregnancy admissions to Hillingdon Hospital between 1967 and 1974 were associated with an in situ IUD,6 as were 14% (3 out of 21) of deaths from ectopic pregnancy in England and Wales between 1973 and 1976.7 If since 1967 14% of hospital admissions for ectopic pregnancy were IUD-related, an annual average of about 450 ectopics in England and Wales would be associated with an in situ device. As in Finland, these 450 ectopic pregnancies would account for much but not all of the increase in ectopic pregnancy incidence. We
acknowledge
the
use
of unpublished data from O.P.C.S.
Epidemiological Monitoring Unit, London School of Hygiene and Tropical Medicine, London WC1E 7HT
NICOLA ROBINSON VALERIE BERAL
COLD-PRESSOR TEST
SIR,-Dr Watson and Professor Littler (Oct. 13, p. 803) the
are
of
measuring the haemodyright emphasise namic response to peripheral cold stimulation when using this test with gated cardiac blood pool scintigraphy in the detection of coronary heart disease (Aug. 18, p. 320). All our subjects had a significant increase in heart rate and mean blood pressure (ratexpressure product), and the responses in patients with coronary artery disease (CAD) or cardiomyopathy were similar to those in controls. The figure shows the comparative to
importance
reported to the British Cardiac Society last month) that, in patients undergoing gated blood pool imaging, cold stimulation detected significantly more CAD patients (41/48, 85%) than did isometric exercise (15/24, 62%) or dynamic exercise (13/21, 62%) (p<0.05), a finding which seems to belittle the magnitude of the hxmodynamic response. Every intervention increased the ratexpressure product, a useful measure of myocardial oxygen demand,but it was possible that cold stimulation in addition caused a reduction of myocardial oxygen supply due to spasm of the coronary resistance vessels in patients with CAD. Support for this hypothesis is provided by Mudge et al .2 who have demonstrated increased coronary vascular resistance during the cold pressor test in patients with CAD but not in normal subjects. Moreover, in our study the degree of impairment of left ventricular ejection fraction (LVEF) in response to cold stimulation did not bear a simple relationship to the magnitude of the haemodynamic response but was principally determined by the severity and extent of CAD; patients with triple-vessel disease had the most profound fall in LVEF, usually greater than 15%. We have also seen episodes of transient bradycardia in 3 patients who had significant increases in systemic blood-pressure in response to the cold stimulation; the ratexpressure product was increased in all cases. Unlike Watson and Littler’s patients, none of ours had hypertension, but lately we have studied 4 hypertensive individuals on no therapy; all had excellent, indeed exaggerated, increases of systemic blood-pressure without bradycardia. We would emphasise that alpha and beta blocking drugs were withdrawn from all our patients; these drugs inhibit the cardiovascular response to cold stimulation. Watson and Littler do not say whether such drugs were withdrawn in their cases, but therapy must be considered when a disappointing response to peripheral cold stimulation is encountered. We conclude that the cold pressor test, despite evoking a smaller increment in ratexpressure product, is not only a simpler intervention but also is more sensitive than dynamic or isometric exercise in the detection of patients with ischxmic heart-disease by gated blood pool scintigraphy. Departments of Cardiology and Nuclear Medicine,
Guy’s Hospital, London SE1 9RT
R. J. WAINWRIGHT D. A. BRENNAND-ROPER M. N. MAISEY E. SOWTON
LYMPHOCYTOTOXIC ANTIBODIES IN HYDRALAZINE-INDUCED LUPUS ERYTHEMATOSUS
responses caused by cold stimulation and cise in CAD patients and controls.
Haemodynamie
exer-
response caused by cold stimulation and different forms of exercise in an extended series of 48 CAD patients and 40 controls. Although there was no difference in the ratexpressure product between controls and patients with CAD during any intervention, it was clear that the load imposed upon the heart was far greater with dynamic exercise (supine or upright) than with isometric exercise or cold stimulation. We were, therefore, surprised to find (in a study
haemodynamic
6. Jonas G. Ectopic pregnancy despite intrauterine contraception: A clue to mode of action of IUCD’s. Br Med J 1975; iii: 467. 7. Department of Health and Social Security. Report on confidential enquiries into maternal deaths in
Office.
England
and Wales. 1973-1975. HM
Stationery
SIR,-Dr Bluestein and colleagues (Oct. 20, p. 816) describe cold-reactive lymphocytotoxic antibodies (LCA) in patients with procainamide-induced lupus. LCA titres were closely related to the severity of the disease, unlike antinuclear antibody titres (ANA). Bluestein et al. propose that LCA, resulting from the expression of new drug-induced antigenic determinants, are an important mechanism in the persistence of drug-induced alteration of central immune regulation. During a prospective study of hydralazine in hypertension we had the opportunity to study seven patients with classical hydralazineinduced lupus erythematosus. We compared the ANA titres, LCA indices, and acetylator phenotypes of these patients with those of forty symptom-free patients on hydralazine in whom a positive ANA had developed. All seven patients had severe arthralgia; four had florid synovitis and one had facial erythema. The ESR was above 30 1. Gobel FL, Nordstrom LA, Nelson RR, Jorgenson CR, Wang Y. The ratepressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 1978; 57: 549-56. 2. Mudge GH, Goldberg S, Gunther S, Mann T, Crossman W. Comparison of metabolic and vasoconstrictor stimuli on coronary vascular resistance in man. Circulation 1979; 59: 544-50.