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URINARY PREGNANETRIOL THROUGHOUT THE MENSTRUAL CYCLE
829
URINARY PREGNANETRIOL THROUGHOUT THE MENSTRUAL CYCLE OBSERVATIONS ON A HEALTHY SUBJECT AND AN ADRENALECTOMISED WOMAN
METHODS developed recently for the quantitative determination of urinary pregnanetriol 1-5 have proved of value in the investigation of adrenocortical dysfunction. Pregnanetriol (5p-pregnane-3fx:17fx:20’x-triol) is present in the urine of healthy men 6 and women,25and is excreted in large amounts in the urine of patients with adrenocortical hyperplasia. 178It is not certain, however, that the adrenal cortex is the only source of the metabolic precursors of urinary pregnanetriol. Moreover, systematic studies of daily excretion during the menstrual cycle and pregnancy have not been reported. The present results, which form part of a wider study, give a comparison of the daily excretion of urinary pregnanediol and urinary pregnanetriol in two women with regular ovulatory cycles. The first subject (aged 26) was a healthy volunteer. The second (aged 45) had undergone bilateral total adrenalectomy for Cushing’s syndrome 3 years previously. She was in good health, being maintained by prednisone 5 mg. and 9x-fluorohydrocortisone 0.1 mg. daily. Apart from the observation of raised urinary pregnanediol excretion in both cycles, evidence of ovulation was obtained from basal temperature records, 1.
Bongiovanni, 94, 180.
A.
M., Clayton, G. W. Bull. Johns Hopk. Hosp. 1954,
2. Bongiovanni, A. M., Eberlein, W. R. Analyt. Chem. 1958, 30, 388. 3. Cox, R. I. J. biol. Chem. 1959, 234, 1693. 4. de Courcy, C. J. Endocrin. 1956, 14, 164. 5. Stern, M. I. ibid. 1957, 16, 180. 6. Cox, R. I., Marrian, G. F. Biochem. J. 1953, 54, 353. 7. Butler, G. C., Marrian, G. F. J. biol. Chem. 1937, 119, 565 8. Mason, H. L., Kepler, E. J. ibid. 1945, 161, 235.
Fig. 2-Adrenalectomised subject: urinary pregnanetriol pregnanediol excretion throughout the menstrual cycle.
and
assays, and vaginal cytology. In the adrenalectomised subject the excretion of urinary neutral 17-ketosteroids and 17-ketogenic steroids fell below the sensitivity of the methods of assay, and this is compatible with the absence of significant secretion from residual or accessory adrenocortical tissue.
urinary oestrogen
METHODS
Urinary pregnanediol and urinary pregnanetriol were determined by the method of Stern5 (which permits measurement of as little as 0-2 mg. per 24-hour specimen of either steroid). In the adrenalectomised subject the urinary pregnanediol was determined also by the method of Klopper et al.,9 and evidence for the specificity of the procedurewas obtained on days 14 and 21 of the cycle by two further chromatographic procedures, originally developed for the determination of urinary pregnanetriol4 and plasma pregnanediol.10 These methods were adapted to permit measurement of either steroid. RESULTS
Figs. 1 and 2 show the amounts of urinary pregnanetriol and pregnanediol excreted throughout the menstrual cycles of the two subjects. The first
subject (fig. 1) showed a cyclical variation pregnanetriol excretion, closely following that of pregnanediol, although at a lower level. The excretion of urinary pregnanetriol varied from 0-4 mg. per 24-hour specimen during the follicular phase to 1-9 mg. per 24 hours during the luteal phase. Pregnanediol excretion varied from 0-5 to 8-8 mg. per 24 hours during the same of
interval. The adrenalectomised subject (fig. 2) also showed increased pregnanetriol and pregnanediol excretion during the second half of the cycle, although the actual quantities were considerably smaller than in the healthy subject. The urinary pregnanediol values obtained by the two methods agreed well except on day 6 of the cycle, when only 0-1mg. per 25 hours was found by the method of Klopper et al.A somewhat analogous increase in pregnanediol excretion was seen in the healthy subject on day 7 of the cycle (fig. 1). We also studied a healthy young woman (aged 18) after the menarche. As in the case of a young in another series,l1 only small amounts of
21/2 years nullipara
Klopper, A. I., Michie, E. A., Brown, J. B. J. Endocrin. 1955, 12, 209. 10. Sommerville, I. F., Deshpande, G. N. J. clin. Endocrin. Metab. 1958, 18, 1223. 11. Brown, J. B., Klopper, A. I., Loraine, J. A. J. Endocrin. 1958, 17, 401. 9.
Fig. 1-Healthy subject:
urinary pregnanetriol and pregnanediol
exctetion throughout the menstrual cycle.
830 were excreted. Urinary pregnanetriol excretion was low also, and there was no sustained increase in either steroid during the cycle.
urinary pregnanediol
SUMMARY AND
CONCLUSIONS
and pregnanetriol detershowed that pregnanetriol excretion was increased during the menstrual cycle. The results obtained in an adrenalectomised woman demonstrated a pattern of urinary pregnanediol excretion in the absence of the contribution from the adrenal
Daily urinary pregnanediol
minations in
two
women
This audiometer is so portable that it can be carried anywhere without difficulty. It has already proved to be extremely useful in many cases where the normal routine assessment was not possible and where the child would not tolerate anything on or close to the ear. The circuit diagram, with some constructional details, is available from the Phonetics Department, University College, London. A more technical description is to be published in the Wireless World. Phonetics Department, University College London, Gower Street, W.C.1
PETER DENES M.SC., A.M.I.E.E.
Audiology Unit,
cortex.
The pattern of urinary pregnanetriol excretion in both subjects suggests the possibility that this steroid may have ovarian as well as adrenocortical precursors. We are indebted to Dr. P. M. F. Bishop for permission to study the adrenalectomised subject, and to the British Empire Cancer Campaign for financial assistance.
MARY T. PICKETT B.SC. Lond.
E. C. KYRIAKIDES MARGARET I. STERN Endocrine Unit, PH.D. Lond., F.R.I.C. Chelsea Hospital for Women and Institute of Obstetrics and Gynaecology, IAN F. SOMMERVILLE Dovehouse Street, London, S.W.3
M.D.,
PH.D.
Edin.
New Inventions A PORTABLE FREE-FIELD AUDIOMETER IT is relatively easy to obtain a pure-tone audiogram from most children who have a mental age of 3 years or above. Sometimes, however, it is impossible to obtain such an audiogram-for instance, if the child is uncooperative or hyperactive. In addition, children under a mental age of 3 years are too immature to be conditioned in the usual play method for obtaining a pure-tone audiogram. In such cases distracting sounds are produced, observations are made of the responses, and degree of hearing loss, if any, is deduced from such observed responses. It is always wise to try to establish some knowledge of hearing throughout the speech range of frequencies. Responses to complex sounds such as rattles, or even to speech sounds only, show awareness of sounds and not necessarily complete comprehension of sound. The use of pitch bars or pitch pipes has given a better picture than the use of more complex sounds, but these are not always pure tones. To try to obtain a more complete picture a small pure-tone audiometer was built in the Phonetics Department of University College, London, for use in a free field situation. It is completely enclosed in a box 51/4 in. X 43/4 in. X 5 in. and weighs 51/4 lb. It incorporates a loudspeaker and produces pure tones of 500 c/s, 1000 c/s, 2000 c/s, and 4000 cis. It is calibrated for a distance of 2 ft. and produces intensity levels of 80 db, 60 db, 20 db, and 0 db relative to a normal threshold at each frequency. It is transistorised and battery-operated. There are two switch controls --one for intensity and one for frequency. A press-button switch turns the sound on and off in a smooth fashion as prescribed by the British Standard for Audiometers. Battery strength can be measured. It was calibrated on five normally hearing adults in a silent room. Therefore in a normal room 0 db and 20 db levels will probably not
be heard.
When a child is restless and continuously on the move, he be followed around with the audiometer. When he does settle a distracting sound, using the audiometer, can be made and any response noted. Over a period of time, using different frequencies and intensities a reliable estimate of hearing may be made. Sometimes children refuse all approaches in a clinical situation, but will respond readily in a home or school situation.
Royal Gray’s
National Throat, Nose and Ear Hospital, Inn Road, London, W.C.1
MICHAEL REED B.SC.
A SIMPLE FLOW-METER AND SAFETY DEVICE FOR THE EXTRACORPOREAL
CIRCULATION MANY varieties of meter, some of them extremely complex, have been used in the laboratory and operating-theatre to measure blood-flow through an extracorporeal circulation. In his review of eight types McMillanmakes no mention of the use of line pressure for gauging the rate of flow. The line carrying blood from pump to patient ends in a cannula inserted into an artery. During perfusion it is customary to measure arterial pressure. If the arterial mean pressure is subtracted from the mean pressure in the line, the resulting value represents the pressure caused by the flow of blood through the cannula at that moment. In the laboratory it is easy to determine the pressure caused by various rates of flow through a cannula, and, in perfusion, to use the pressure value as a 2 measure of flow. For clinical purposes a glass A glass U-tube containing mercury U-tube containing merfor the measurement pf line to a is connected cury pressure in an extracorporeal branch from the arterial circulation. Excessive pressure line. By adjusting a screw arising from obstruction to the
clip on the branch line, one can measure either puls-
the mercury to make with an electrode and activate an electrical bell.
line
causes
contact
atile or mean pressure. In open heart surgery, obstruction of the arterial line or cannula by external pressure, kinking, or displacement is an ever-present hazard. Such obstruction instantly causes a rise in line pressure, and this may be employed to sound a warning signal. The mercury is used as one electrode of an electrical bell system, and the second electrode is placed at a suitable height above the meniscus in the ascending limb of the u-tube (see figure). The arterial line filter-chamber designed by Dr. D. G. Melrose and manufactured by New Electronics Products Ltd. bears a port to which may be attached a branch line leading to the manometer.
can
P. G. F. NIXON General Infirmary, Leeds.
M.E., Durh.
M.R.C.P.
Research Fellow in Thoracic
Surgery
1. McMillan, I. K. R. Extracorporeal Circulation. Springfield, III. 1958. 2. Cleland, W. P., Beard, A. J. W., Bentall, H. H., Bishop, M. B., Braimbridge, M. V., Bromley, L. L., Goodwin, J. F., Hollman, A., Kerr, W. F., Lloyd-Jones, E. B., Melrose, D. G., Telivuo, L. J. Brit. med.J. 1958, ii, 1369.
URINARY PREGNANETRIOL THROUGHOUT THE MENSTRUAL CYCLE OBSERVATIONS ON A HEALTHY SUBJECT AND AN ADRENALECTOMISED WOMAN
METHODS developed recently for the quantitative determination of urinary pregnanetriol 1-5 have proved of value in the investigation of adrenocortical dysfunction. Pregnanetriol (5p-pregnane-3fx:17fx:20’x-triol) is present in the urine of healthy men 6 and women,25and is excreted in large amounts in the urine of patients with adrenocortical hyperplasia. 178It is not certain, however, that the adrenal cortex is the only source of the metabolic precursors of urinary pregnanetriol. Moreover, systematic studies of daily excretion during the menstrual cycle and pregnancy have not been reported. The present results, which form part of a wider study, give a comparison of the daily excretion of urinary pregnanediol and urinary pregnanetriol in two women with regular ovulatory cycles. The first subject (aged 26) was a healthy volunteer. The second (aged 45) had undergone bilateral total adrenalectomy for Cushing’s syndrome 3 years previously. She was in good health, being maintained by prednisone 5 mg. and 9x-fluorohydrocortisone 0.1 mg. daily. Apart from the observation of raised urinary pregnanediol excretion in both cycles, evidence of ovulation was obtained from basal temperature records, 1.
Bongiovanni, 94, 180.
A.
M., Clayton, G. W. Bull. Johns Hopk. Hosp. 1954,
2. Bongiovanni, A. M., Eberlein, W. R. Analyt. Chem. 1958, 30, 388. 3. Cox, R. I. J. biol. Chem. 1959, 234, 1693. 4. de Courcy, C. J. Endocrin. 1956, 14, 164. 5. Stern, M. I. ibid. 1957, 16, 180. 6. Cox, R. I., Marrian, G. F. Biochem. J. 1953, 54, 353. 7. Butler, G. C., Marrian, G. F. J. biol. Chem. 1937, 119, 565 8. Mason, H. L., Kepler, E. J. ibid. 1945, 161, 235.
Fig. 2-Adrenalectomised subject: urinary pregnanetriol pregnanediol excretion throughout the menstrual cycle.
and
assays, and vaginal cytology. In the adrenalectomised subject the excretion of urinary neutral 17-ketosteroids and 17-ketogenic steroids fell below the sensitivity of the methods of assay, and this is compatible with the absence of significant secretion from residual or accessory adrenocortical tissue.
urinary oestrogen
METHODS
Urinary pregnanediol and urinary pregnanetriol were determined by the method of Stern5 (which permits measurement of as little as 0-2 mg. per 24-hour specimen of either steroid). In the adrenalectomised subject the urinary pregnanediol was determined also by the method of Klopper et al.,9 and evidence for the specificity of the procedurewas obtained on days 14 and 21 of the cycle by two further chromatographic procedures, originally developed for the determination of urinary pregnanetriol4 and plasma pregnanediol.10 These methods were adapted to permit measurement of either steroid. RESULTS
Figs. 1 and 2 show the amounts of urinary pregnanetriol and pregnanediol excreted throughout the menstrual cycles of the two subjects. The first
subject (fig. 1) showed a cyclical variation pregnanetriol excretion, closely following that of pregnanediol, although at a lower level. The excretion of urinary pregnanetriol varied from 0-4 mg. per 24-hour specimen during the follicular phase to 1-9 mg. per 24 hours during the luteal phase. Pregnanediol excretion varied from 0-5 to 8-8 mg. per 24 hours during the same of
interval. The adrenalectomised subject (fig. 2) also showed increased pregnanetriol and pregnanediol excretion during the second half of the cycle, although the actual quantities were considerably smaller than in the healthy subject. The urinary pregnanediol values obtained by the two methods agreed well except on day 6 of the cycle, when only 0-1mg. per 25 hours was found by the method of Klopper et al.A somewhat analogous increase in pregnanediol excretion was seen in the healthy subject on day 7 of the cycle (fig. 1). We also studied a healthy young woman (aged 18) after the menarche. As in the case of a young in another series,l1 only small amounts of
21/2 years nullipara
Klopper, A. I., Michie, E. A., Brown, J. B. J. Endocrin. 1955, 12, 209. 10. Sommerville, I. F., Deshpande, G. N. J. clin. Endocrin. Metab. 1958, 18, 1223. 11. Brown, J. B., Klopper, A. I., Loraine, J. A. J. Endocrin. 1958, 17, 401. 9.
Fig. 1-Healthy subject:
urinary pregnanetriol and pregnanediol
exctetion throughout the menstrual cycle.
830 were excreted. Urinary pregnanetriol excretion was low also, and there was no sustained increase in either steroid during the cycle.
urinary pregnanediol
SUMMARY AND
CONCLUSIONS
and pregnanetriol detershowed that pregnanetriol excretion was increased during the menstrual cycle. The results obtained in an adrenalectomised woman demonstrated a pattern of urinary pregnanediol excretion in the absence of the contribution from the adrenal
Daily urinary pregnanediol
minations in
two
women
This audiometer is so portable that it can be carried anywhere without difficulty. It has already proved to be extremely useful in many cases where the normal routine assessment was not possible and where the child would not tolerate anything on or close to the ear. The circuit diagram, with some constructional details, is available from the Phonetics Department, University College, London. A more technical description is to be published in the Wireless World. Phonetics Department, University College London, Gower Street, W.C.1
PETER DENES M.SC., A.M.I.E.E.
Audiology Unit,
cortex.
The pattern of urinary pregnanetriol excretion in both subjects suggests the possibility that this steroid may have ovarian as well as adrenocortical precursors. We are indebted to Dr. P. M. F. Bishop for permission to study the adrenalectomised subject, and to the British Empire Cancer Campaign for financial assistance.
MARY T. PICKETT B.SC. Lond.
E. C. KYRIAKIDES MARGARET I. STERN Endocrine Unit, PH.D. Lond., F.R.I.C. Chelsea Hospital for Women and Institute of Obstetrics and Gynaecology, IAN F. SOMMERVILLE Dovehouse Street, London, S.W.3
M.D.,
PH.D.
Edin.
New Inventions A PORTABLE FREE-FIELD AUDIOMETER IT is relatively easy to obtain a pure-tone audiogram from most children who have a mental age of 3 years or above. Sometimes, however, it is impossible to obtain such an audiogram-for instance, if the child is uncooperative or hyperactive. In addition, children under a mental age of 3 years are too immature to be conditioned in the usual play method for obtaining a pure-tone audiogram. In such cases distracting sounds are produced, observations are made of the responses, and degree of hearing loss, if any, is deduced from such observed responses. It is always wise to try to establish some knowledge of hearing throughout the speech range of frequencies. Responses to complex sounds such as rattles, or even to speech sounds only, show awareness of sounds and not necessarily complete comprehension of sound. The use of pitch bars or pitch pipes has given a better picture than the use of more complex sounds, but these are not always pure tones. To try to obtain a more complete picture a small pure-tone audiometer was built in the Phonetics Department of University College, London, for use in a free field situation. It is completely enclosed in a box 51/4 in. X 43/4 in. X 5 in. and weighs 51/4 lb. It incorporates a loudspeaker and produces pure tones of 500 c/s, 1000 c/s, 2000 c/s, and 4000 cis. It is calibrated for a distance of 2 ft. and produces intensity levels of 80 db, 60 db, 20 db, and 0 db relative to a normal threshold at each frequency. It is transistorised and battery-operated. There are two switch controls --one for intensity and one for frequency. A press-button switch turns the sound on and off in a smooth fashion as prescribed by the British Standard for Audiometers. Battery strength can be measured. It was calibrated on five normally hearing adults in a silent room. Therefore in a normal room 0 db and 20 db levels will probably not
be heard.
When a child is restless and continuously on the move, he be followed around with the audiometer. When he does settle a distracting sound, using the audiometer, can be made and any response noted. Over a period of time, using different frequencies and intensities a reliable estimate of hearing may be made. Sometimes children refuse all approaches in a clinical situation, but will respond readily in a home or school situation.
Royal Gray’s
National Throat, Nose and Ear Hospital, Inn Road, London, W.C.1
MICHAEL REED B.SC.
A SIMPLE FLOW-METER AND SAFETY DEVICE FOR THE EXTRACORPOREAL
CIRCULATION MANY varieties of meter, some of them extremely complex, have been used in the laboratory and operating-theatre to measure blood-flow through an extracorporeal circulation. In his review of eight types McMillanmakes no mention of the use of line pressure for gauging the rate of flow. The line carrying blood from pump to patient ends in a cannula inserted into an artery. During perfusion it is customary to measure arterial pressure. If the arterial mean pressure is subtracted from the mean pressure in the line, the resulting value represents the pressure caused by the flow of blood through the cannula at that moment. In the laboratory it is easy to determine the pressure caused by various rates of flow through a cannula, and, in perfusion, to use the pressure value as a 2 measure of flow. For clinical purposes a glass A glass U-tube containing mercury U-tube containing merfor the measurement pf line to a is connected cury pressure in an extracorporeal branch from the arterial circulation. Excessive pressure line. By adjusting a screw arising from obstruction to the
clip on the branch line, one can measure either puls-
the mercury to make with an electrode and activate an electrical bell.
line
causes
contact
atile or mean pressure. In open heart surgery, obstruction of the arterial line or cannula by external pressure, kinking, or displacement is an ever-present hazard. Such obstruction instantly causes a rise in line pressure, and this may be employed to sound a warning signal. The mercury is used as one electrode of an electrical bell system, and the second electrode is placed at a suitable height above the meniscus in the ascending limb of the u-tube (see figure). The arterial line filter-chamber designed by Dr. D. G. Melrose and manufactured by New Electronics Products Ltd. bears a port to which may be attached a branch line leading to the manometer.
can
P. G. F. NIXON General Infirmary, Leeds.
M.E., Durh.
M.R.C.P.
Research Fellow in Thoracic
Surgery
1. McMillan, I. K. R. Extracorporeal Circulation. Springfield, III. 1958. 2. Cleland, W. P., Beard, A. J. W., Bentall, H. H., Bishop, M. B., Braimbridge, M. V., Bromley, L. L., Goodwin, J. F., Hollman, A., Kerr, W. F., Lloyd-Jones, E. B., Melrose, D. G., Telivuo, L. J. Brit. med.J. 1958, ii, 1369.