- Email: [email protected]
hCG-BETA-SUBUNIT RADIOIMMUNOASSAY IN GYNÆCOLOGICAL EMERGENCIES
484
Why, then, do O’Connor et al. assert that "the fetal scalp in labour provides a totally unrepresentative capillary bed"? Their own data6indeed show a poor correlation between fetal scalp TcP02 and umbilical arterial PO,. However, the fact that their data were derived from studies carried out just before the delivery of the fetal head, at "crowning", and using a TcP02 electrode makes such a sweeping conclusion quite unjustified. Furthermore, the experiment in their Nov. 3 paper does not take into account the fact that uterine contractions are intermittent. The likelihood is that at the end of each contraction, there is venous congestion in the scalp followed by rapid reperfusion of the skin with arterialised blood between contractions. All the longitudinal studies referred to show a sharp fall in acid-base and blood gases in the latter part of the second stage of labour, presumably due to a variable combination of genuine fetal asphyxia and compression of the head against the perineum. Furthermore considerable skill and experience are required to obtain reliable readings from the TcP02 electrode applied to the fetal scalp.7 It seems unreasonable to condemn the fetal scalp as a site for the collection of the fetal blood on the basis of such limited data and in the face of the many studies that have come to a contrary view. The fetal scalp is not an ideal sampling site; caput formation, although not frequent, is evidence of a pressure effect, and the technique of fetal blood sampling is complicated by the presence of amniotic fluid and maternal blood. It is, however, the only site available and by and large has proved valuable to the obstetrician. Department of Obstetrics and Gynæcology, St Mary’s Hospital Medical School, London W2 1PG
chotic illnesses and for severe behaviour disorder. It therefore appears that prolonged usage of various anticonvulsant and tranquillising drugs, sometimes in high dosages, did not have a carcinogenic effect on the liver in our epileptic patients. In our sample the incidence of cancer of the gastrointestinal tract is high (59 cases) and appears to be still increasing, even allowing for the patients’ prolonged lifespan. The next most frequently affected site was the breast (15 female) but the incidence of cancer of the respiratory system3 is low (4 cases). Out of 120 Down syndrome patients who died only 2 had cancer (1male with cancer of the stomach and the 1 female with carcinoma of the gallbladder previously noted). Stoke Park Hospital, Stapleton, Bristol BS16
J. JANCAR
1QU
hCG-BETA-SUBUNIT RADIOIMMUNOASSAY IN GYNÆCOLOGICAL EMERGENCIES
SIR,-We would like to report our experience on the routine of the rapid human chorionic gonadotrophin (hCG) betasubunit radioimmunoassay (RIA) described by Professor Seppala and colleagues and discussed editorially in The Lancet of Jan. 26. We studied 200 patients with an acute gynxcological emergency and found a positive hCG-RIA test in 57 cases use
hCG
SERUM
LUCA FUSI
(POSITIVE AND NEGATIVE RESULTS)
CLINICAL FINDINGS IN
R. W. BEARD
200
IN RELATION TO
PATIENTS WITH ACUTE
GYNECOLOGICAL EMERGENCIES
ANTICONVULSANT DRUGS AND CANCER
SIR,-White
et
al.’ recorded
an excess
mortality rate in epi-
leptic patients compared with that in the general population of England and Wales. They also noted that the incidence of malignant disease was significantly higher, but there were no liver tumours (only 1 gallbladder carcinoma) in their sample and they suggested that it is unlikely that the liver tumours produced on feeding phenobarbitone to mice are indicators of major human risk. We have recently updated our previous forty year review2 of the patients who died in four mental handicap hospitals (Stoke Park Group of Hospitals). Our sample differs from that of White et al., but the hospital population during forty years was fairly stable-just above 1600 patients of which over 300 were epileptics. However, during the past few years we have been reducing the hospital beds and on Jan. 1, 1980, we had 1240 patients (288 epileptics). The total number of deaths between January, 1956 and Jan1980, was 1245 of whom 102 died from cancer. No case of cancer of the liver was observed among epileptics, but 1 case of hepatoma and 1 case of carcinoma of the gallbladder occurred among the non-epileptic patients, neither having received any drugs. All our epileptics were on anticonvulsant drugs for many years. Similarly a number of patients were for many years receiving various tranquillising drugs for superimposed psy-
uary,
6. O’Connor MC, Hytten FE. Aspects of perinatal transcutaneous PO; monitoring. Arch Dis Child (in press). 7. Rooth G, Fall O, Huch A, Huch R. Integrated interpretation of fetal heart rate, intrauterine pressure and fetal transcutaneous PO2. Proceedings of foetal and neonatal physiological measurements conference (Oxford,
1979). (In press.) 1. White
S, McLean AEM, Harland C. Anticonvulsant drugs and cancer. Lancet 1979, ii: 458-60. 2. Jancar MP, Jancar J. Cancer and mental retardation: a forty year review. Bristol Med
Chir J 1977; 92:
3-7.
*
for infertility in previous cycle. proliferative endometrial state, repeated test negative. 2nd case: secretory endometrial state, laparotomy negative. intrauterine device, secretory endometrial state, laparotomy negative. hCG
t lst
treatment
case:
(29%). 21 ectopic pregnancies were verified by laparotomy (see table), and 20 of them (95%) had a positive serum-hCG test, while a routine urinary pregnancy test was positive in only 3 out of 16 cases (19%). The sensitivity’ of the rapid serum hCG test was 98%, predictive value 93%, and specificity 97%. Ultrasound scans (real time) on 38 patients with positive results revealed signs of intrauterine pregnancy in 12 cases. There were 11 ectopic pregnancies in which ultrasonic examination correctly excluded intrauterine pregnancy, but there also were 15 cases in which intrauterine pregnancy could not be demonstrated by ultrasonography in the absence of ectopic pregnancy. The latter cases included very early pregnancies and abortions verified by follow-up and/or endometrial histology. Our larger material confirms the results of Sepata et al.! and shows that rapid semiquantitative serum-hCG RIA 3. Jancar J. Cancer in the long-stay hospitals. Br J Psychiat 1979; 134: 550-51. 1. Gordon YB, Lewis JD, Pendlebury DJ, Leighton M, Gold J. Is measurement of placental function and maternal weight worthwhile? Lancet 1978;i 1001-03.
485 is highly effective in distinguishing pregnancy-related disorders from other causes of low abdominal pain and bleeding. Ultrasonic examination may give further inforination on the site of pregnancy in some but not all hCG-positive cases.
ants
test
ent
produced. Comprehensive Sickle Cell Center, Department of Pathology, University of Chicago, Chicago, Illinois 60637, U.S.A.
RUTANEN
Department of Obstetrics and Gynæcology,
Jorvi District Hospital, 02740 Espoo 74, Finland
should be further investigated to determine how the prespattern of distribution of the G6PD polymorphism is
EEVA-MARJA HEIKKI TARJANNE JUHO HUOVINEN MARTTI IKONEN
SHELLY C. BERNSTEIN JAMES E. BOWMAN
INADVERTENT OVERDOSE OF PARENTERAL TERBUTALINE
G6PD/MALARIA HYPOTHESIS: A BALANCED OR
SiR,—To our knowledge, this is only the second case-report where the recommended subcutaneous dose of terbutaline (0-25 mg) was confused with the recommended starting oral dose (2-5mg).’I A 35-year-old woman with insulin-requiring diabetes was admitted to hospital with a 2 day history of lower abdominal and back pain following an amniocentesis. Her 21 week pregnancy was complicated by large uterine fibroids. Premature labour was suspected and an intravenous infusion of terbutaline was started at a rate of 0.25 mg/h. After about 12 h, during which time her heart-rate ranged from 90 to 114/min, it was decided to switch her to subcutaneous terbutaline 0-25 mg. However, she received an s.c. dose of 2-5mg in error 1 h after the continuous i.v. infusion of terbutaline was discontinued. 10 min after the s.c. dose non-radiating substernal chest pressure developed with a tachycardia of 150/min. An ECG showed inferolateral ischxmia and she was admitted to the coronary-care unit to rule.out a myocardial infarction. In the coronary-care unit, examination was remarkable for a pulse-rate of 150/min regular, blood-pressure 120/80 mm Hg, and a II/VI systolic ejection murmur. Her ECG revealed a sinus tachycardia of 150/min with ST segment depression in leads I, II, III, F and in V4 and V6 with inverted T waves in III and F. All medications except insulin were withheld. Her cardiac course remained essentially benign, the tachycardia resolving after 10 h and cardiac enzymes over 2 days being essentially normal. The ECG reverted to normal over these 2 days. Terbutaline was not successful in preventing the premature labour as she had a spontaneous abortion. a relatively specific (32 adrenergic receptor stimulant, is effective in reversible bronchospasm at s.c. doses of 0-25 mg or oral doses of 2.5 mg.2 It has also shown efficacy as an investigational agent in managing premature labour, both orally and parenterally.3.4 Adverse effects are generally mild and include muscle tremor, dizziness, nervousness, palpitations, tachycardia, and blood-pressure changes. With parenteral administration and larger oral doses, there is loss of &bgr;2-receptor selectivity with greater cardiovascular side-
TRANSIENT POLYMORPHISM
SIR,-Twenty years have elapsed since Allison’ and Motulsky2 suggested that the high gene frequency of glucose-6phosphate dehydrogenase (G6PD) deficiency in populations endemic for falciparum malaria might be maintained as an X-linked polymorphism by a balance of selective forces. Dr Martin (Jan. 5, p. 51) proposes a mechanism based on recent clinical and in vitro studies3 by which G6PD deficiency, oxidant stress, and malaria interact. Individuals with GdBor GdB/GdB are not protected against malaria and are not susceptible to oxidant stress. Individuals with Gd B-lGd B- and GdBare protected from lethal malaria but are also under negative selection from oxidant stress. The female heterozygote GdB/GdB-, who has both the normal and the deficient alleles, is protected from negative selection of favism and from falciparum malaria. Martin states that this will create a situation whereby balanced polymorphism could arise. However, the polymorphism will be balanced only if in the GdB/GdB and GdB individuals the susceptibility to malaria is greater than the protection against oxidant stress alone, and in the GdB-/GdB- and GdB- individuals the susceptibility to oxidant stress is greater than the protection against malaria. That is to say, the fitnesses of the homozygotes and of the hemizygotes must be less than that of the heterozygotes.. If either of these conditions is not met, then the polymorphism will be transient with the eventual loss’of one allele and the fixation of the other. This is based on a selection model assuming an X-linked locus with two alleles, no mutation, and genotypeindependent zygotic sex ratio, also assuming that total fitness is the product of fitness components.4 The magnitudes of opposing selective pressures, which vary from one population to another in different environments, will determine whether the polymorphism will be balanced or transient. Furthermore, Eaton5 and Friedman3 have shown that the malaria parasite itself exerts an oxidant stress on affected red cells. While this may in one sense contribute to the protection of GdB/GdB- heterozygotes from malaria, it also adds to other oxidant stress, such as fava beans and viral hepatitis. This additional stress’ may lead to increased relative fitness of GdB/GdB and GdBindividuals and at the same time decreased relative fitness of GdB-/GdB- and GdB- individuals, to such an extent that a transient polymorphism with the gradual fixation of the GdB allele and the eventual loss of the GdB- allele will
Terbutaline,
effects. 1,5,6 Doctors and
’
ensue.
Finally, the G6PD polymorphism in many parts of Africa is three-allele (GdA, Gd^-, GdB) polymorphism with GdA and GDA- alleles having similar geographic distributions. As yet, we have no reasonable explanation for the maintenance of the Gd^ allele. While Martin offers an attractive hypothesis for the mechanism of protection against malaria afforded by G6PD deficiency, the complex interaction of infectious disease, environmental factors as yet not know, and other genetic varia
1. Allison AC.
Glucose-6-phosphate dehydrogenase deficiency in red blood cells of East Africans. Nature 1960; 186: 531-32. 2. Motulsky AG. Metabolic polymorphisms and the role of infectious disease in human evolution. Hum Biol 1960, 32: 28-62. 3. Friedman MJ. Oxidant damage mediates variant red cell resistance to malaria. Nature 1979; 280: 245-47. 4. Nagylaki T. Selection in one- and two-locus systems. Lecture notes in biomathematics: vol. XV. Berlin: Springer-Verlag, 1977. 5 Eaton JW, Eckman JR, Berger E, Jacob HS. Suppression of malaria infection by oxidant-sensitive host erythrocytes. Nature 1976; 264: 758-60.
nurses must exercise caution when prescribing, administering this drug. The parenteral preparations of terbutaline (’Bricanyl’, Astra; ’Brethine’, Geigy) are both singleuse glass ampoules containing 1 mg/ml; thus’each -ampoule contains four normal doese of 0.25 mg each. Simply misplacing the decimal point can result in significant adverse effects, as in our patient. Furthermore, since the rest of each ampoule is thrown away, changing the packaging of this drug to singleor
dose ampoules could save lives and money. New York Hospital, New York, N.Y. 10021, U.S.A.
ROBERT D. BRANDSTETTER VINCENT GOTZ
Pond A. Problems with terbutaline. N Engl Med J 1977; 296: 821. 2. Dulfano MJ, Glass P. The bronchodilator effects of terbutaline: route of administration and patterns of response. Ann Allergy 1976; 37: 357-66. 3. Ryden G. The effect of salbutamol and terbutaline in the management of premature labor. Acta Obstet Gynecol Scand 1977; 56: 293-96. 4. Wallace RL, Caldwell DL, Ansbacher R, et al. Inhibition of premature labor by terbutaline. Obstet Gynecol 1978; 51: 387-92. 5. Sackner MA, Dougherty R, Watson H, et al. Hemodynamic effects of epinephrine and terbutaline in normal man. Chest 1975; 68: 616-24. 6. Smith PR, Heurich AE, Leffler CT, et al. A comparative study of subcutaneously administered terbutaline and epinephrine in the treatment of acute bronchial asthma. Chest 1977; 71: 129-34. 1.
Lawyer C,
Why, then, do O’Connor et al. assert that "the fetal scalp in labour provides a totally unrepresentative capillary bed"? Their own data6indeed show a poor correlation between fetal scalp TcP02 and umbilical arterial PO,. However, the fact that their data were derived from studies carried out just before the delivery of the fetal head, at "crowning", and using a TcP02 electrode makes such a sweeping conclusion quite unjustified. Furthermore, the experiment in their Nov. 3 paper does not take into account the fact that uterine contractions are intermittent. The likelihood is that at the end of each contraction, there is venous congestion in the scalp followed by rapid reperfusion of the skin with arterialised blood between contractions. All the longitudinal studies referred to show a sharp fall in acid-base and blood gases in the latter part of the second stage of labour, presumably due to a variable combination of genuine fetal asphyxia and compression of the head against the perineum. Furthermore considerable skill and experience are required to obtain reliable readings from the TcP02 electrode applied to the fetal scalp.7 It seems unreasonable to condemn the fetal scalp as a site for the collection of the fetal blood on the basis of such limited data and in the face of the many studies that have come to a contrary view. The fetal scalp is not an ideal sampling site; caput formation, although not frequent, is evidence of a pressure effect, and the technique of fetal blood sampling is complicated by the presence of amniotic fluid and maternal blood. It is, however, the only site available and by and large has proved valuable to the obstetrician. Department of Obstetrics and Gynæcology, St Mary’s Hospital Medical School, London W2 1PG
chotic illnesses and for severe behaviour disorder. It therefore appears that prolonged usage of various anticonvulsant and tranquillising drugs, sometimes in high dosages, did not have a carcinogenic effect on the liver in our epileptic patients. In our sample the incidence of cancer of the gastrointestinal tract is high (59 cases) and appears to be still increasing, even allowing for the patients’ prolonged lifespan. The next most frequently affected site was the breast (15 female) but the incidence of cancer of the respiratory system3 is low (4 cases). Out of 120 Down syndrome patients who died only 2 had cancer (1male with cancer of the stomach and the 1 female with carcinoma of the gallbladder previously noted). Stoke Park Hospital, Stapleton, Bristol BS16
J. JANCAR
1QU
hCG-BETA-SUBUNIT RADIOIMMUNOASSAY IN GYNÆCOLOGICAL EMERGENCIES
SIR,-We would like to report our experience on the routine of the rapid human chorionic gonadotrophin (hCG) betasubunit radioimmunoassay (RIA) described by Professor Seppala and colleagues and discussed editorially in The Lancet of Jan. 26. We studied 200 patients with an acute gynxcological emergency and found a positive hCG-RIA test in 57 cases use
hCG
SERUM
LUCA FUSI
(POSITIVE AND NEGATIVE RESULTS)
CLINICAL FINDINGS IN
R. W. BEARD
200
IN RELATION TO
PATIENTS WITH ACUTE
GYNECOLOGICAL EMERGENCIES
ANTICONVULSANT DRUGS AND CANCER
SIR,-White
et
al.’ recorded
an excess
mortality rate in epi-
leptic patients compared with that in the general population of England and Wales. They also noted that the incidence of malignant disease was significantly higher, but there were no liver tumours (only 1 gallbladder carcinoma) in their sample and they suggested that it is unlikely that the liver tumours produced on feeding phenobarbitone to mice are indicators of major human risk. We have recently updated our previous forty year review2 of the patients who died in four mental handicap hospitals (Stoke Park Group of Hospitals). Our sample differs from that of White et al., but the hospital population during forty years was fairly stable-just above 1600 patients of which over 300 were epileptics. However, during the past few years we have been reducing the hospital beds and on Jan. 1, 1980, we had 1240 patients (288 epileptics). The total number of deaths between January, 1956 and Jan1980, was 1245 of whom 102 died from cancer. No case of cancer of the liver was observed among epileptics, but 1 case of hepatoma and 1 case of carcinoma of the gallbladder occurred among the non-epileptic patients, neither having received any drugs. All our epileptics were on anticonvulsant drugs for many years. Similarly a number of patients were for many years receiving various tranquillising drugs for superimposed psy-
uary,
6. O’Connor MC, Hytten FE. Aspects of perinatal transcutaneous PO; monitoring. Arch Dis Child (in press). 7. Rooth G, Fall O, Huch A, Huch R. Integrated interpretation of fetal heart rate, intrauterine pressure and fetal transcutaneous PO2. Proceedings of foetal and neonatal physiological measurements conference (Oxford,
1979). (In press.) 1. White
S, McLean AEM, Harland C. Anticonvulsant drugs and cancer. Lancet 1979, ii: 458-60. 2. Jancar MP, Jancar J. Cancer and mental retardation: a forty year review. Bristol Med
Chir J 1977; 92:
3-7.
*
for infertility in previous cycle. proliferative endometrial state, repeated test negative. 2nd case: secretory endometrial state, laparotomy negative. intrauterine device, secretory endometrial state, laparotomy negative. hCG
t lst
treatment
case:
(29%). 21 ectopic pregnancies were verified by laparotomy (see table), and 20 of them (95%) had a positive serum-hCG test, while a routine urinary pregnancy test was positive in only 3 out of 16 cases (19%). The sensitivity’ of the rapid serum hCG test was 98%, predictive value 93%, and specificity 97%. Ultrasound scans (real time) on 38 patients with positive results revealed signs of intrauterine pregnancy in 12 cases. There were 11 ectopic pregnancies in which ultrasonic examination correctly excluded intrauterine pregnancy, but there also were 15 cases in which intrauterine pregnancy could not be demonstrated by ultrasonography in the absence of ectopic pregnancy. The latter cases included very early pregnancies and abortions verified by follow-up and/or endometrial histology. Our larger material confirms the results of Sepata et al.! and shows that rapid semiquantitative serum-hCG RIA 3. Jancar J. Cancer in the long-stay hospitals. Br J Psychiat 1979; 134: 550-51. 1. Gordon YB, Lewis JD, Pendlebury DJ, Leighton M, Gold J. Is measurement of placental function and maternal weight worthwhile? Lancet 1978;i 1001-03.
485 is highly effective in distinguishing pregnancy-related disorders from other causes of low abdominal pain and bleeding. Ultrasonic examination may give further inforination on the site of pregnancy in some but not all hCG-positive cases.
ants
test
ent
produced. Comprehensive Sickle Cell Center, Department of Pathology, University of Chicago, Chicago, Illinois 60637, U.S.A.
RUTANEN
Department of Obstetrics and Gynæcology,
Jorvi District Hospital, 02740 Espoo 74, Finland
should be further investigated to determine how the prespattern of distribution of the G6PD polymorphism is
EEVA-MARJA HEIKKI TARJANNE JUHO HUOVINEN MARTTI IKONEN
SHELLY C. BERNSTEIN JAMES E. BOWMAN
INADVERTENT OVERDOSE OF PARENTERAL TERBUTALINE
G6PD/MALARIA HYPOTHESIS: A BALANCED OR
SiR,—To our knowledge, this is only the second case-report where the recommended subcutaneous dose of terbutaline (0-25 mg) was confused with the recommended starting oral dose (2-5mg).’I A 35-year-old woman with insulin-requiring diabetes was admitted to hospital with a 2 day history of lower abdominal and back pain following an amniocentesis. Her 21 week pregnancy was complicated by large uterine fibroids. Premature labour was suspected and an intravenous infusion of terbutaline was started at a rate of 0.25 mg/h. After about 12 h, during which time her heart-rate ranged from 90 to 114/min, it was decided to switch her to subcutaneous terbutaline 0-25 mg. However, she received an s.c. dose of 2-5mg in error 1 h after the continuous i.v. infusion of terbutaline was discontinued. 10 min after the s.c. dose non-radiating substernal chest pressure developed with a tachycardia of 150/min. An ECG showed inferolateral ischxmia and she was admitted to the coronary-care unit to rule.out a myocardial infarction. In the coronary-care unit, examination was remarkable for a pulse-rate of 150/min regular, blood-pressure 120/80 mm Hg, and a II/VI systolic ejection murmur. Her ECG revealed a sinus tachycardia of 150/min with ST segment depression in leads I, II, III, F and in V4 and V6 with inverted T waves in III and F. All medications except insulin were withheld. Her cardiac course remained essentially benign, the tachycardia resolving after 10 h and cardiac enzymes over 2 days being essentially normal. The ECG reverted to normal over these 2 days. Terbutaline was not successful in preventing the premature labour as she had a spontaneous abortion. a relatively specific (32 adrenergic receptor stimulant, is effective in reversible bronchospasm at s.c. doses of 0-25 mg or oral doses of 2.5 mg.2 It has also shown efficacy as an investigational agent in managing premature labour, both orally and parenterally.3.4 Adverse effects are generally mild and include muscle tremor, dizziness, nervousness, palpitations, tachycardia, and blood-pressure changes. With parenteral administration and larger oral doses, there is loss of &bgr;2-receptor selectivity with greater cardiovascular side-
TRANSIENT POLYMORPHISM
SIR,-Twenty years have elapsed since Allison’ and Motulsky2 suggested that the high gene frequency of glucose-6phosphate dehydrogenase (G6PD) deficiency in populations endemic for falciparum malaria might be maintained as an X-linked polymorphism by a balance of selective forces. Dr Martin (Jan. 5, p. 51) proposes a mechanism based on recent clinical and in vitro studies3 by which G6PD deficiency, oxidant stress, and malaria interact. Individuals with GdBor GdB/GdB are not protected against malaria and are not susceptible to oxidant stress. Individuals with Gd B-lGd B- and GdBare protected from lethal malaria but are also under negative selection from oxidant stress. The female heterozygote GdB/GdB-, who has both the normal and the deficient alleles, is protected from negative selection of favism and from falciparum malaria. Martin states that this will create a situation whereby balanced polymorphism could arise. However, the polymorphism will be balanced only if in the GdB/GdB and GdB individuals the susceptibility to malaria is greater than the protection against oxidant stress alone, and in the GdB-/GdB- and GdB- individuals the susceptibility to oxidant stress is greater than the protection against malaria. That is to say, the fitnesses of the homozygotes and of the hemizygotes must be less than that of the heterozygotes.. If either of these conditions is not met, then the polymorphism will be transient with the eventual loss’of one allele and the fixation of the other. This is based on a selection model assuming an X-linked locus with two alleles, no mutation, and genotypeindependent zygotic sex ratio, also assuming that total fitness is the product of fitness components.4 The magnitudes of opposing selective pressures, which vary from one population to another in different environments, will determine whether the polymorphism will be balanced or transient. Furthermore, Eaton5 and Friedman3 have shown that the malaria parasite itself exerts an oxidant stress on affected red cells. While this may in one sense contribute to the protection of GdB/GdB- heterozygotes from malaria, it also adds to other oxidant stress, such as fava beans and viral hepatitis. This additional stress’ may lead to increased relative fitness of GdB/GdB and GdBindividuals and at the same time decreased relative fitness of GdB-/GdB- and GdB- individuals, to such an extent that a transient polymorphism with the gradual fixation of the GdB allele and the eventual loss of the GdB- allele will
Terbutaline,
effects. 1,5,6 Doctors and
’
ensue.
Finally, the G6PD polymorphism in many parts of Africa is three-allele (GdA, Gd^-, GdB) polymorphism with GdA and GDA- alleles having similar geographic distributions. As yet, we have no reasonable explanation for the maintenance of the Gd^ allele. While Martin offers an attractive hypothesis for the mechanism of protection against malaria afforded by G6PD deficiency, the complex interaction of infectious disease, environmental factors as yet not know, and other genetic varia
1. Allison AC.
Glucose-6-phosphate dehydrogenase deficiency in red blood cells of East Africans. Nature 1960; 186: 531-32. 2. Motulsky AG. Metabolic polymorphisms and the role of infectious disease in human evolution. Hum Biol 1960, 32: 28-62. 3. Friedman MJ. Oxidant damage mediates variant red cell resistance to malaria. Nature 1979; 280: 245-47. 4. Nagylaki T. Selection in one- and two-locus systems. Lecture notes in biomathematics: vol. XV. Berlin: Springer-Verlag, 1977. 5 Eaton JW, Eckman JR, Berger E, Jacob HS. Suppression of malaria infection by oxidant-sensitive host erythrocytes. Nature 1976; 264: 758-60.
nurses must exercise caution when prescribing, administering this drug. The parenteral preparations of terbutaline (’Bricanyl’, Astra; ’Brethine’, Geigy) are both singleuse glass ampoules containing 1 mg/ml; thus’each -ampoule contains four normal doese of 0.25 mg each. Simply misplacing the decimal point can result in significant adverse effects, as in our patient. Furthermore, since the rest of each ampoule is thrown away, changing the packaging of this drug to singleor
dose ampoules could save lives and money. New York Hospital, New York, N.Y. 10021, U.S.A.
ROBERT D. BRANDSTETTER VINCENT GOTZ
Pond A. Problems with terbutaline. N Engl Med J 1977; 296: 821. 2. Dulfano MJ, Glass P. The bronchodilator effects of terbutaline: route of administration and patterns of response. Ann Allergy 1976; 37: 357-66. 3. Ryden G. The effect of salbutamol and terbutaline in the management of premature labor. Acta Obstet Gynecol Scand 1977; 56: 293-96. 4. Wallace RL, Caldwell DL, Ansbacher R, et al. Inhibition of premature labor by terbutaline. Obstet Gynecol 1978; 51: 387-92. 5. Sackner MA, Dougherty R, Watson H, et al. Hemodynamic effects of epinephrine and terbutaline in normal man. Chest 1975; 68: 616-24. 6. Smith PR, Heurich AE, Leffler CT, et al. A comparative study of subcutaneously administered terbutaline and epinephrine in the treatment of acute bronchial asthma. Chest 1977; 71: 129-34. 1.
Lawyer C,