- Email: [email protected]
ISOTRETINOIN AND CONTRACEPTION
752
that, at high frequency, creatinine can be clearly and unambiguously assigned and distinguished from creatine, unlike the situation at 90 MHz shown by Yamaguchi et al. At high frequency a large number of peaks are also resolved in the aromatic region (5-10 ppm). NMR urinalysis shows great promise as an aid to rapid disease diagnosis. However, quantitative measurements should be interpreted cautiously until interferences have been fully investigated.High frequency NMR is also expensive, but it should be possible to design cheaper machines for clinical work.
3. Knudson AG Jr, Meadows AT. Regression of neuroblastoma IV-s: a genetic hypothesis. N Engl J Med 1980; 22: 1254-56. 4. Jaffe N. Neuroblastoma: review of the literature and an examination of factors contributing to its enigmatic character. Cancer Treat Rev 1976; 3: 61-82. 5. Stokes SH, Thomas PRM, Perez CA, et al. Stage IV-s neuroblastoma: results with definitive therapy. Cancer 1984; 53: 2083-86. 6. Evans AE, Brand W, Lorimier A, et al. Results in children with local and regional neuroblastoma managed with and without vincristine, cyclophosphamide, and imidazolecarboxamide: a report from the Children’s Cancer Study Group. Am J Clin Oncol 1984; 6: 3-8. 7. Pastore G, Antonelli R, Fine W, et al. Late effects of treatment of cancer in infancy. Med Pediatr Oncol 1982; 10: 369-75.
Toxicology Unit, Department of Pharmacology,
A LOOPHOLE IN THE PHENYLKETONURIA
School
of Pharmacy, University of London,
SCREENING PROGRAMME
JEREMY
London WC1
Department of Chemistry, Birkbeck College, University of London, London WC1E 7HX
Department of Medicine, St Thomas’ Hospital Medical School, London SE1
K. NICHOLSON
PETER J. SADLER JOHN R. BALES SANDRA M. JUUL
ANDREW F. MACLEOD PETER H. SONKSEN
Higham DP, Howe I, Nicholson JK, Sadler PJ. Use of high resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem 1984; 30: 426-32. 2. Bock JL. Analysis of serum by high field proton nuclear magnetic resonance. Clin Chem 1. Bales JR,
1982; 28: 1873-77.
RA, Buckingham MJ, Hawkes GE. Spin-echo proton nuclear magnetic resonance detection of normal and abnormal metabolites in plasma and urine Biochem Soc Trans 1983; 11: 374-75. Nicholson JK, Buckingham MJ, Sadler PJ. High resolution H NMR studies of vertebrate blood and plasma. Biochem J 1983; 211: 605-15. Nicholson JK, O’Flynn M, Sadler PJ, et al. Proton nuclear magnetic resonance studies of serum, plasma and urine from fasting normal, and diabetic subjects. Biochem J 1984; 217: 365-75. Nicholson JK, Timbrell JA, Higham DP, Sadler PJ. Mercury and cadmium nephrotoxicity and the detection of abnormal urinary metabolites by proton NMR spectroscopy. Human Toxicol 1984; 3: 334-35. Traube M, Bock JL, Boyer JL D-lactic acidosis after jejunoileal bypass: Identification of organic anions by nuclear magnetic resonance spectroscopy. Ann Intern Med
3. Iles
4. 5.
6.
7.
1983; 98: 171-73.
SCREENING FOR NEUROBLASTOMA
SIR,-Dr Sawada and colleagues (Aug 4, p 271) describe a screening programme in infants in Japan and present incidence for neuroblastoma in the first year of life. The 16 cancers detected were not incident cases of neuroblastoma but prevalent cases of the detectable preclinical phase of the disease The prevalence in their programme is 16/281 939 or 56 - 8 x 10- . If we assume an incidence ratel of the disease in the first year of life in Japanese children similar to that in Turin2we can calculate a mean duration of the DPCP of neuroblastoma of about 2 years (56-8x 10’-32’4x 10-6). This implies that most of the prevalent cases would have become evident after the first year oflife, and that a lead time (the period between detection by screening and diagnosis in the absence of screening) of about one year for each screendetected case should be taken into account in comparisons of survival rates. Spontaneous regressions are well documented for neuroblastoma in infants, especially for stage IVs disease.3,4 Close observation with minimal or no treatment is considered a wise clinical approach for stage I, II, and IVs neuroblastoma,s,6 in view of the unpredictable and the late effects of biological behaviour4of the disease 7 chemotherapy and radiotherapy. Sawada et al-by inflating the number of incident cases in the first year of life and by not considering the lead time and the possibility of spontaneous regression so that some prevalent cases of DPCP might never have presented clinically or been treated with potentially toxic therapies-may be overestimating the benefit of their mass rates
(DPCP2.1
screening. Department of Cancer Epidemiology, University of Turin, 10126 Turin, Italy
GUIDO PASTORE FRANCO MERLETTI CORRADO MAGNANI
P, Morrison A. Basic issues in population screening for cancer. J Natl Cancer Inst 1980; 64: 1263-72. 2. Pastore G, Magnani C, Zanetti R, et al. Incidence of cancer in children in the province of Torino (Italy) 1967-74. Eur J Cancer Oncol 1981; 17: 1337-41. 1. Cole
SlR,-A 23-year-old woman gave birth in July of this year to a growth-retarded, microcephalic infant (birthweight 2 - 36 kg, head circumference 29.55 cm) at 41 weeks’ gestation. A maternal aunt, aged 14 years, had been treated for phenylketonuria; the mother’s serum phenylalanine was 1500 mol/1, and the infant’s 70 mol/1. The mother therefore has unrecognised phenylketonuria with normal intellectual development (she had an average school performance and had been employed as a factory worker). The infant’s microcephaly is almost certainly caused by maternal phenylketonuria, and delayed intellectual development is to be expected. Although the mother had told both her general practitioner and the midwife at the antenatal booking visit that she had a sister with phenylketonuria, neither she nor her attendants were aware of the possible implications. The 14-year-old sister had been diagnosed in 1970, one of the first cases of phenylketonuria to be detected following the introduction of neonatal screening by blood phenylalanine in the South West Region. Her older sister, born in 1960, was not tested for phenylketonuria at that time since her development seemed normal. It is possible that she was screened as a baby by the urinary phenistix test, which was in use during the 1960s. This method had a falsewith less than 1 % for blood spot negative rate of30-50%, compared I phenylalanine estimations. There may be many unsuspected cases of phenylketonuria in the general population born before reliable neonatal screening was introduced. Such women cause irreversible damage to their unborn children unless their blood phenylalanine is brought under control before conception.2It may be impossible to carry out a general screen to detect all cases at risk, but clearly any sisters of known cases, especially those born before 1970, should have a blood phenylalanine test. At present, paediatricians are not advised to screen well female siblings of children with phenylketonuria. We fear that unless such a policy is implemented, further infants with potentially avoidable handicap will be born to unsuspecting mothers. Plymouth General Hospital, Plymouth PL4 7LY Department of Biochemistry, Southmead Hospital,
R. E. APPLETON
J. H. BAUMER
J. B. HOLTON
Bristol
screening for phenylketonuria in the U.K. 1964-78. Report of Steering Committee for MRC/DHSS Phenylketonuria Register. Br
1. Routine neonatal
M.R C.
Med J 1981; 282: 1680-84. R, Levy H. Maternal phenylketonuria and hyperphenylalaninaemia: an international survey of the outcome of treated and untreated pregnancies. N Engl J Med 1980; 303: 1202-08.
2. Lenke
ISOTRETINOIN AND CONTRACEPTION
SIR,-Lancet correspondence 1-3 on the teratogenicity of isotretinoin has stressed how important it is for women receiving isotretinoin to be given effective contraception. Combined oral contraceptive steroids (OCS) are probably the most effective form of contraception. Does isotretinoin interfere with the contraceptive effect of OCS? We studied nine women aged 19-29 who were taking isotretinoin (0-55 mg/kg) for severe pustular acne. All had been taking OCS for at least 3 months before starting isotretinoin. Blood samples were taken on days 7, 8, 9, and 10 of the contraceptive cycle before starting isotretinoin and in the first and third cycles of OCS use after starting isotretinoin. Plasma concentrations of OCS were measured
753
by specific and sensitive radioimmunoassay,4,S
and isotretinoin did interfere with these assays. Isotretinoin was very effective in these patients with acne. Plasma concentrations of ethinyloestradiol were 30 -° 9±3Ipg/ml (mean±SE) in the control cycle and 32-1 ±4 -3and 32 - 2±4 -8 pg/ml in the two cycles after starting isotretinoin. Plasma concentrations of levonorgestrel similarly were not altered significantly by isotretinoin therapy (1 - 58:t0 .85 ng/ml in the control cycle and 1 - -26±0-63 and 1 - -34±0-62 ng/ml in the two cycles after starting isotretinoin). Blood samples taken on days 21 and 22 of each cycle were analysed for plasma progesterone concentration which was always less than 400 pg/ml. The findings indicate that isotretinoin, at least in this dose, does interact adversely with oral contraceptive steroids. not The progesterone concentrations clearly indicate effective contraception in all patients. Thus women receiving isotretinoin in a dose of 0 5 mg/kg can rely on their OCS for contraceptive control. It seems unlikely that any interaction would be seen with the 1 - 0 mg/kg dose of isotretinoin that is now widely recommended in the USA. not
We thank the World Health Organisation, Mersey and Roche Products Ltd for financial support.
Regional Health
Authority,
M. ORME D.J. BACK M. A. SHAW W. L. ALLEN
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3BX
J. TJIA W.J. CUNLIFFE D. H. JONES
Department of Dermatology, Leeds General
Infirmary
1. Rosa FW. Teratogenicity of isotretinoin. Lancet 1983; ii: 513. 2 Braun JT, Franciosi RA, Mastri AR, Drake RM, O’Neil BL. Isotretinoin dysmorphic syndrome Lancet 1984; i: 506-07. 3 Hill RM. Isotretinoin teratogenicity. Lancet 1984, i: 1465. 4. Back DJ, Breckenridge AM, Crawford, FE, MacIver M, Orme ML’E, Rowe PH,
Watts MJ. An investigation of the pharmacokinetics of ethinylestradiol in women using radioimmunoassay. Contraception 1979; 20: 263-73. 5. Back DJ, Bates M, Breckenridge AM, Hall JM, MacIver, M, Orme ML’E, Park BK, Rowe PH. The pharmacokinetics of levonorgestrel and ethinylestradiol in women. Studies with Ovran and Ovranette. Contraception 1981; 23: 229-39.
SIR,-Digital subtraction angiography (DSA) has made possible diagnostic studies of the abdominal aorta, extracranial carotid, pelvic, renal, and extremity arteries with venous injections of X-ray contrast material. However, limited temporal and spatial resolution and misregistration due to cardiac motion hamper the application of venous DSA to coronary arteries.’ These difficulties can be diminished by high-speed data acquisition and precise electrocardiographic timing of subtraction masks. A new high bandwidth data system has been developed by constructing a high-speed interface between a Fastbus (IEEE-P960) crate and a computer (VAX 11/780 ; Digital Equipment Corp).
A and B
are
elsewhere. The protocol for this study was approved by the hospital committee on human research. Informed consent was obtained from each patient. A right atrial (RA) power injection of 30 ml of X-ray contrast material (’Renografin 76’; Squibb) was delivered through a no 6 NIH catheter (USCI) at 20 ml/s. In four of five consecutive patients, with two RA injections of X-ray contrast material and two views, we have visualised substantial portions of coronary arteries and the atherosclerotic lesions therein (figure). High quality videodensitometric analysis of regional myocardial X-ray contrast washout was also obtained. The findings were validated with direct intracoronary angiography in each patient. We are not aware of any previous studies of human coronary arteries using a venous RA injection of X-ray contrast material and, high-speed memory. This new technique should be helpful in the study of patients with acute myocardial infarction-a more heterogeneous group than previously thought.5,6 It also should prove useful as an improved analytical method for the physiological assessment of coronary artery obstructions in man.
JOHN MORRISON Department of Medicine, North Shore University Hospital, Manhasset, NY 11030, USA; and Department of Medicine, Cornell University Medical College, New York
LAWRENCE ONG ERIC SISKIND MANIKARNIKA SRINIVASAN MERYLL FROST VELLORE PADMANABHAN PETER REISER
CA, Crummy AB. Diagnosis of cardiovascular disease by digital subtraction angiography. Science 1981; 214: 761-65. US NIM Committee. Fastbus: Modular high speed data acquisition and control system for high energy physics and other applications. Springfield, Virginia: Office of Energy Research, US Department of Energy. Obtainable from National Technical Information Service, US Department of Commerce. December, 1983. Siskind E, Ong L, Srinivasan M, Frost M, Reiser P, Morrison J. High bandwidth Fastbus based data acquisition system for imaging coronary arteries. IEEE Trans
1. Mistretta
VENOUS CORONARY ANGIOGRAPHY
Left anterior
Fastbus2 is a modular data transport and computer interconnection developed to fulfil certain future needs of high energy This new system can acquire 8-16 bit pixel values research. physics at instantaneous rates up to 45 megapixels/s, transporting these data via Fastbus at 160 megabytes into high-speed memory (Intel) while simultaneously reading data out of memory into a computerFastbus host interface. All data pathways were designed to acquire biplane data at 60 frames/s. In typical current uniplane runs, 300 512 x 512 pixel frames of 8 bit pixel data comprising 75 megabytes of data are acquired in 10 s of 30 frame/s operation. The actual source of the data is a digital microbeam television camera (Hamamatsu) viewing an X-ray image intensifier (CPG-20’; CGR). Details of the hardware design of this system have appeared 3,4 scheme
2.
3.
Nucl Sci 1983, NS-30: 3775-78. EJ, Ong L, Srinivasan M, Frost M, Reiser P, Morrison J. Experience with a Fastbus based data acquisition system for imaging coronary arteries. IEEE Trans Nucl Sci 1984; NS-31: 230-35. 5. Ong L, Reiser P, Coromilas J, Scherr L, Morrison J. Rapid creatine kinase-MB release and left ventricular function in acute myocardial infarction: evidence for 1983; 309: 1-6. spontaneous reperfusion N Engl Med J 6. Editorial. Intracoronary thrombolysis Lancet 1983; ii: 606.
4. Siskind
descending coronary artery (LAD).
from digital venous study; B is computer subtraction of A; C is standard intracoronary Arrow indicates LAD. Circumflex branch obscured by opacified ventricle in B.
cineangiogram
that, at high frequency, creatinine can be clearly and unambiguously assigned and distinguished from creatine, unlike the situation at 90 MHz shown by Yamaguchi et al. At high frequency a large number of peaks are also resolved in the aromatic region (5-10 ppm). NMR urinalysis shows great promise as an aid to rapid disease diagnosis. However, quantitative measurements should be interpreted cautiously until interferences have been fully investigated.High frequency NMR is also expensive, but it should be possible to design cheaper machines for clinical work.
3. Knudson AG Jr, Meadows AT. Regression of neuroblastoma IV-s: a genetic hypothesis. N Engl J Med 1980; 22: 1254-56. 4. Jaffe N. Neuroblastoma: review of the literature and an examination of factors contributing to its enigmatic character. Cancer Treat Rev 1976; 3: 61-82. 5. Stokes SH, Thomas PRM, Perez CA, et al. Stage IV-s neuroblastoma: results with definitive therapy. Cancer 1984; 53: 2083-86. 6. Evans AE, Brand W, Lorimier A, et al. Results in children with local and regional neuroblastoma managed with and without vincristine, cyclophosphamide, and imidazolecarboxamide: a report from the Children’s Cancer Study Group. Am J Clin Oncol 1984; 6: 3-8. 7. Pastore G, Antonelli R, Fine W, et al. Late effects of treatment of cancer in infancy. Med Pediatr Oncol 1982; 10: 369-75.
Toxicology Unit, Department of Pharmacology,
A LOOPHOLE IN THE PHENYLKETONURIA
School
of Pharmacy, University of London,
SCREENING PROGRAMME
JEREMY
London WC1
Department of Chemistry, Birkbeck College, University of London, London WC1E 7HX
Department of Medicine, St Thomas’ Hospital Medical School, London SE1
K. NICHOLSON
PETER J. SADLER JOHN R. BALES SANDRA M. JUUL
ANDREW F. MACLEOD PETER H. SONKSEN
Higham DP, Howe I, Nicholson JK, Sadler PJ. Use of high resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. Clin Chem 1984; 30: 426-32. 2. Bock JL. Analysis of serum by high field proton nuclear magnetic resonance. Clin Chem 1. Bales JR,
1982; 28: 1873-77.
RA, Buckingham MJ, Hawkes GE. Spin-echo proton nuclear magnetic resonance detection of normal and abnormal metabolites in plasma and urine Biochem Soc Trans 1983; 11: 374-75. Nicholson JK, Buckingham MJ, Sadler PJ. High resolution H NMR studies of vertebrate blood and plasma. Biochem J 1983; 211: 605-15. Nicholson JK, O’Flynn M, Sadler PJ, et al. Proton nuclear magnetic resonance studies of serum, plasma and urine from fasting normal, and diabetic subjects. Biochem J 1984; 217: 365-75. Nicholson JK, Timbrell JA, Higham DP, Sadler PJ. Mercury and cadmium nephrotoxicity and the detection of abnormal urinary metabolites by proton NMR spectroscopy. Human Toxicol 1984; 3: 334-35. Traube M, Bock JL, Boyer JL D-lactic acidosis after jejunoileal bypass: Identification of organic anions by nuclear magnetic resonance spectroscopy. Ann Intern Med
3. Iles
4. 5.
6.
7.
1983; 98: 171-73.
SCREENING FOR NEUROBLASTOMA
SIR,-Dr Sawada and colleagues (Aug 4, p 271) describe a screening programme in infants in Japan and present incidence for neuroblastoma in the first year of life. The 16 cancers detected were not incident cases of neuroblastoma but prevalent cases of the detectable preclinical phase of the disease The prevalence in their programme is 16/281 939 or 56 - 8 x 10- . If we assume an incidence ratel of the disease in the first year of life in Japanese children similar to that in Turin2we can calculate a mean duration of the DPCP of neuroblastoma of about 2 years (56-8x 10’-32’4x 10-6). This implies that most of the prevalent cases would have become evident after the first year oflife, and that a lead time (the period between detection by screening and diagnosis in the absence of screening) of about one year for each screendetected case should be taken into account in comparisons of survival rates. Spontaneous regressions are well documented for neuroblastoma in infants, especially for stage IVs disease.3,4 Close observation with minimal or no treatment is considered a wise clinical approach for stage I, II, and IVs neuroblastoma,s,6 in view of the unpredictable and the late effects of biological behaviour4of the disease 7 chemotherapy and radiotherapy. Sawada et al-by inflating the number of incident cases in the first year of life and by not considering the lead time and the possibility of spontaneous regression so that some prevalent cases of DPCP might never have presented clinically or been treated with potentially toxic therapies-may be overestimating the benefit of their mass rates
(DPCP2.1
screening. Department of Cancer Epidemiology, University of Turin, 10126 Turin, Italy
GUIDO PASTORE FRANCO MERLETTI CORRADO MAGNANI
P, Morrison A. Basic issues in population screening for cancer. J Natl Cancer Inst 1980; 64: 1263-72. 2. Pastore G, Magnani C, Zanetti R, et al. Incidence of cancer in children in the province of Torino (Italy) 1967-74. Eur J Cancer Oncol 1981; 17: 1337-41. 1. Cole
SlR,-A 23-year-old woman gave birth in July of this year to a growth-retarded, microcephalic infant (birthweight 2 - 36 kg, head circumference 29.55 cm) at 41 weeks’ gestation. A maternal aunt, aged 14 years, had been treated for phenylketonuria; the mother’s serum phenylalanine was 1500 mol/1, and the infant’s 70 mol/1. The mother therefore has unrecognised phenylketonuria with normal intellectual development (she had an average school performance and had been employed as a factory worker). The infant’s microcephaly is almost certainly caused by maternal phenylketonuria, and delayed intellectual development is to be expected. Although the mother had told both her general practitioner and the midwife at the antenatal booking visit that she had a sister with phenylketonuria, neither she nor her attendants were aware of the possible implications. The 14-year-old sister had been diagnosed in 1970, one of the first cases of phenylketonuria to be detected following the introduction of neonatal screening by blood phenylalanine in the South West Region. Her older sister, born in 1960, was not tested for phenylketonuria at that time since her development seemed normal. It is possible that she was screened as a baby by the urinary phenistix test, which was in use during the 1960s. This method had a falsewith less than 1 % for blood spot negative rate of30-50%, compared I phenylalanine estimations. There may be many unsuspected cases of phenylketonuria in the general population born before reliable neonatal screening was introduced. Such women cause irreversible damage to their unborn children unless their blood phenylalanine is brought under control before conception.2It may be impossible to carry out a general screen to detect all cases at risk, but clearly any sisters of known cases, especially those born before 1970, should have a blood phenylalanine test. At present, paediatricians are not advised to screen well female siblings of children with phenylketonuria. We fear that unless such a policy is implemented, further infants with potentially avoidable handicap will be born to unsuspecting mothers. Plymouth General Hospital, Plymouth PL4 7LY Department of Biochemistry, Southmead Hospital,
R. E. APPLETON
J. H. BAUMER
J. B. HOLTON
Bristol
screening for phenylketonuria in the U.K. 1964-78. Report of Steering Committee for MRC/DHSS Phenylketonuria Register. Br
1. Routine neonatal
M.R C.
Med J 1981; 282: 1680-84. R, Levy H. Maternal phenylketonuria and hyperphenylalaninaemia: an international survey of the outcome of treated and untreated pregnancies. N Engl J Med 1980; 303: 1202-08.
2. Lenke
ISOTRETINOIN AND CONTRACEPTION
SIR,-Lancet correspondence 1-3 on the teratogenicity of isotretinoin has stressed how important it is for women receiving isotretinoin to be given effective contraception. Combined oral contraceptive steroids (OCS) are probably the most effective form of contraception. Does isotretinoin interfere with the contraceptive effect of OCS? We studied nine women aged 19-29 who were taking isotretinoin (0-55 mg/kg) for severe pustular acne. All had been taking OCS for at least 3 months before starting isotretinoin. Blood samples were taken on days 7, 8, 9, and 10 of the contraceptive cycle before starting isotretinoin and in the first and third cycles of OCS use after starting isotretinoin. Plasma concentrations of OCS were measured
753
by specific and sensitive radioimmunoassay,4,S
and isotretinoin did interfere with these assays. Isotretinoin was very effective in these patients with acne. Plasma concentrations of ethinyloestradiol were 30 -° 9±3Ipg/ml (mean±SE) in the control cycle and 32-1 ±4 -3and 32 - 2±4 -8 pg/ml in the two cycles after starting isotretinoin. Plasma concentrations of levonorgestrel similarly were not altered significantly by isotretinoin therapy (1 - 58:t0 .85 ng/ml in the control cycle and 1 - -26±0-63 and 1 - -34±0-62 ng/ml in the two cycles after starting isotretinoin). Blood samples taken on days 21 and 22 of each cycle were analysed for plasma progesterone concentration which was always less than 400 pg/ml. The findings indicate that isotretinoin, at least in this dose, does interact adversely with oral contraceptive steroids. not The progesterone concentrations clearly indicate effective contraception in all patients. Thus women receiving isotretinoin in a dose of 0 5 mg/kg can rely on their OCS for contraceptive control. It seems unlikely that any interaction would be seen with the 1 - 0 mg/kg dose of isotretinoin that is now widely recommended in the USA. not
We thank the World Health Organisation, Mersey and Roche Products Ltd for financial support.
Regional Health
Authority,
M. ORME D.J. BACK M. A. SHAW W. L. ALLEN
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3BX
J. TJIA W.J. CUNLIFFE D. H. JONES
Department of Dermatology, Leeds General
Infirmary
1. Rosa FW. Teratogenicity of isotretinoin. Lancet 1983; ii: 513. 2 Braun JT, Franciosi RA, Mastri AR, Drake RM, O’Neil BL. Isotretinoin dysmorphic syndrome Lancet 1984; i: 506-07. 3 Hill RM. Isotretinoin teratogenicity. Lancet 1984, i: 1465. 4. Back DJ, Breckenridge AM, Crawford, FE, MacIver M, Orme ML’E, Rowe PH,
Watts MJ. An investigation of the pharmacokinetics of ethinylestradiol in women using radioimmunoassay. Contraception 1979; 20: 263-73. 5. Back DJ, Bates M, Breckenridge AM, Hall JM, MacIver, M, Orme ML’E, Park BK, Rowe PH. The pharmacokinetics of levonorgestrel and ethinylestradiol in women. Studies with Ovran and Ovranette. Contraception 1981; 23: 229-39.
SIR,-Digital subtraction angiography (DSA) has made possible diagnostic studies of the abdominal aorta, extracranial carotid, pelvic, renal, and extremity arteries with venous injections of X-ray contrast material. However, limited temporal and spatial resolution and misregistration due to cardiac motion hamper the application of venous DSA to coronary arteries.’ These difficulties can be diminished by high-speed data acquisition and precise electrocardiographic timing of subtraction masks. A new high bandwidth data system has been developed by constructing a high-speed interface between a Fastbus (IEEE-P960) crate and a computer (VAX 11/780 ; Digital Equipment Corp).
A and B
are
elsewhere. The protocol for this study was approved by the hospital committee on human research. Informed consent was obtained from each patient. A right atrial (RA) power injection of 30 ml of X-ray contrast material (’Renografin 76’; Squibb) was delivered through a no 6 NIH catheter (USCI) at 20 ml/s. In four of five consecutive patients, with two RA injections of X-ray contrast material and two views, we have visualised substantial portions of coronary arteries and the atherosclerotic lesions therein (figure). High quality videodensitometric analysis of regional myocardial X-ray contrast washout was also obtained. The findings were validated with direct intracoronary angiography in each patient. We are not aware of any previous studies of human coronary arteries using a venous RA injection of X-ray contrast material and, high-speed memory. This new technique should be helpful in the study of patients with acute myocardial infarction-a more heterogeneous group than previously thought.5,6 It also should prove useful as an improved analytical method for the physiological assessment of coronary artery obstructions in man.
JOHN MORRISON Department of Medicine, North Shore University Hospital, Manhasset, NY 11030, USA; and Department of Medicine, Cornell University Medical College, New York
LAWRENCE ONG ERIC SISKIND MANIKARNIKA SRINIVASAN MERYLL FROST VELLORE PADMANABHAN PETER REISER
CA, Crummy AB. Diagnosis of cardiovascular disease by digital subtraction angiography. Science 1981; 214: 761-65. US NIM Committee. Fastbus: Modular high speed data acquisition and control system for high energy physics and other applications. Springfield, Virginia: Office of Energy Research, US Department of Energy. Obtainable from National Technical Information Service, US Department of Commerce. December, 1983. Siskind E, Ong L, Srinivasan M, Frost M, Reiser P, Morrison J. High bandwidth Fastbus based data acquisition system for imaging coronary arteries. IEEE Trans
1. Mistretta
VENOUS CORONARY ANGIOGRAPHY
Left anterior
Fastbus2 is a modular data transport and computer interconnection developed to fulfil certain future needs of high energy This new system can acquire 8-16 bit pixel values research. physics at instantaneous rates up to 45 megapixels/s, transporting these data via Fastbus at 160 megabytes into high-speed memory (Intel) while simultaneously reading data out of memory into a computerFastbus host interface. All data pathways were designed to acquire biplane data at 60 frames/s. In typical current uniplane runs, 300 512 x 512 pixel frames of 8 bit pixel data comprising 75 megabytes of data are acquired in 10 s of 30 frame/s operation. The actual source of the data is a digital microbeam television camera (Hamamatsu) viewing an X-ray image intensifier (CPG-20’; CGR). Details of the hardware design of this system have appeared 3,4 scheme
2.
3.
Nucl Sci 1983, NS-30: 3775-78. EJ, Ong L, Srinivasan M, Frost M, Reiser P, Morrison J. Experience with a Fastbus based data acquisition system for imaging coronary arteries. IEEE Trans Nucl Sci 1984; NS-31: 230-35. 5. Ong L, Reiser P, Coromilas J, Scherr L, Morrison J. Rapid creatine kinase-MB release and left ventricular function in acute myocardial infarction: evidence for 1983; 309: 1-6. spontaneous reperfusion N Engl Med J 6. Editorial. Intracoronary thrombolysis Lancet 1983; ii: 606.
4. Siskind
descending coronary artery (LAD).
from digital venous study; B is computer subtraction of A; C is standard intracoronary Arrow indicates LAD. Circumflex branch obscured by opacified ventricle in B.
cineangiogram