- Email: [email protected]
TIME OF OVULATION IN RELATION TO CYCLE LENGTH
1029
symptoms. This, however, did not seem to affect the chances of successful resuscitation. In all our patients arterial lactate was increased: levels ranged from 16 mg. per 100 ml. to 130 mg. (normal 8-14 mg.). The size of the increase correlated with the degree of metabolic acidosis indicated by depression of the plasma-bicarbonate. This suggests that the acidosis of cardiac arrest is, in fact, lactic acidosis and that it results from tissue hypoxia. That neither arterial lactate nor bicarbonate correlated with the arterial oxygen saturation is not surprising since cardiac output is the major determinant of tissue oxygenation under these circumstances. There is evidence that metabolic acidosis lowers the threshold for ventricular fibrillation (Gerst et al. 1963), may induce and sustain cardiac asystole (Stewart 1964), and depresses myocardial contractility (Thrower et al. 1961). We have therefore assumed its presence in cardiac arrest and have attempted to correct it as rapidly as possible without waiting for the results of blood analyses. Mellemgaard and Astrup (1960) showed that the dilution space for bicarbonate given rapidly is approximately 30% of the body-weight. If the bicarbonate level at the start of resuscitation is assumed to be about 15 mEq. per litre (fig. 2), the dose (in mEq.) needed to restore it to 25 mEq. per litre can be calculated as 3 x body-weight (kg.). This is the dose we have given initially. If the patient responds and is not hypotensive before its administration is complere it is discontinued and the arterial bicarbonate is then measured. If the patient does not respond the dose is repeated over the next ten to fifteen minutes. This dosage In such a may, on occasion, lead to moderate alkalosis. dangerous situation it is less to be feared than continuing acidosis.
Summary The treatment of 128 patients with cardiac arrest is outlined. 23 survived. Over 3 years 254 patients have been treated and 40 (15-8%) have survived. Metabolic acidosis and raised arterial-lactate levels were found in most patients soon after arrest. Correction of the acidosis with intravenous sodium bicarbonate was found beneficial. Appropriate dosage is
suggested. We are grateful to Dr. M. McGregor and Dr. A. L. Johnson for their encouragement and help with this manuscript. We should also like to thank the nurses of the cardiorespiratory service without whose help this series would not have been possible. This study was aided by grants from the John A. Hartford Foundation. REFERENCES
Astrup, P. (1956) Scand. J. clin. Lab. Invest. 8, 33. Ball, W. C. Jr., Stewart, P. B., Newsham, L. G. S., Bates, D. V. (1962) J. clin. Invest. 41, 519 Baringer, J. R., Salzman, E. W., Jones, W. A., Freidlich, A. L. (1961) New Engl. J. Med. 265, 62. Barker, S. B., Summerson, W. H. (1941) J. biol. Chem. 138, 535. Brown, K. W. G., MacMillan, R. L., Forbath, N., Melgrano, F., Scott, J. W. (1963) Lancet, ii, 349. Clark, D. I. (1962) J. Amer. med. Ass. 181, 337. Gerst, P. H., Fleming, W. H., Malin, J. R. (1963) Physiologist, 6, 185. Himmelhoch, S. R., Dekker, A., Gazzaniga, A. B., Like, A. A. (1964) New Engl. J. Med. 270, 118. Jude, J. B., Kouwenhoven, W. B., Knickerbocker, G. G. (1961) J. Amer. med. Ass. 178, 1063. Klassen, G. A., Broadhurst, C., Peretz, D. I., Johnson, A. L. (1963) Lancet, i, 1290. Lown, B., Amarasingham, R., Neuman, J. (1962) J. Amer. med. Ass. 182, 548. Mellemgaard, K., Astrup, P. (1960) Scand. J. clin. lab. Invest. 12, 187. Robin, E. D., Julian, J. G., Travis, D. M., Crump, C. A. (1959) New Engl. Med. J. 260, 586. Shipman, J. H., McCrady, W., Bradford, A. A. (1962) Amer. J. Cardiol. 10, 551 Stewart, J. S. S. (1964) Brit. med. J. i, 476. Sykes, M. K., Ahmed, N. (1963) Lancet, ii, 347. Thrower, W. B., Darby, T. D., Aldinger, E. E. (1961) Arch. Surg. 82, 56.
TIME OF OVULATION IN RELATION TO CYCLE LENGTH E. T. BELL B.Sc. Durh., Ph.D. Edin. MEMBER OF SCIENTIFIC STAFF
J. A. LORAINE M.B., Ph.D., D.Sc. Edin., F.R.C.P.E. DIRECTOR
MEDICAL RESEARCH COUNCIL CLINICAL ENDOCRINOLOGY
RESEARCH
UNIT,
UNIVERSITY OF EDINBURGH
MANY methods have been described for the determination of ovulation in human subjects (see Hartman 1936, Speck 1959); but in the opinion of Sturgis and Pommerenke (1950), Speck (1959), and others no single test is entirely satisfactory. Hormone-excretion patterns in ovulatory menstrual cycles were reviewed by Loraine and Bell (1963), who emphasised that such cycles were characterised by midcycle and luteal-phase peaks of oestrogen excretion together with a luteal-phase rise in pregnanediol and pregnanetriol output. The peak of oestrogen excretion at midcycle is believed to be closely associated with ovulation itself (Brown 1960), and this peak has been used to determine the day of the cycle on which this event takes place. The aim of the present communication is to attempt to correlate the time of ovulation, judged by the midcycle peak of oestrone and oestradiol output, with the duration of the menstrual cycle. Materials and Methods
Clinical A total of 45 menstrual cycles in 31 women is reported. In all subjects the duration of the cycle was recorded, day 1 being the first day of menstruation. The cycles were subdivided into the following three groups. 1. A series of 23 cycles from 18 normally menstruating women who had received no form of hormonal medication either before or during the investigation. Data derived from some of these cycles have already been published (Brown et al. 1958, Loraine and Bell 1963). 2. A series of 12 cycles in 7 subjects who had previously been treated with various progestogen-oestrogen mixtures as oral contraceptives for periods of time ranging from 9 to 44 calendar months. Details of the subjects studied together with the compounds administered were given by Loraine et al. (1963, 1965). The data reported herein were derived from the first, and in some cases the second, post-treatment cycle. 3. A series of 10 cycles from 6 women who had received treatment for one cycle with one of the following compoundscompound 33,828 (Imperial Chemical Industries Ltd.), norethisterone and its acetate (Schering AG, Berlin), and dydrogesterone (’Duphaston’, Philips Duphar). In the subjects treated with compound 33,828, norethisterone, and norethisterone acetate ovulation was inhibited during drug administration, but with dydrogesterone such an inhibition was unusual (Bell et al. 1962, Brown et al. 1962, Bell and Loraine 1965). The results reported herein are those obtained from the cycles immediately following therapy by the various compounds.
Hormone All the
Assays
collected complete 24-hour urine samples continuously throughout the period of investigation. The excretion of oestradiol, oestrone, and oestriol was measured by the method of Brown (1955) in either 24-hour or 48-hour urine pools. women
Results "
For the purpose of the study " midcycle was defined as the length of the cycle divided by two-e.g., in a 28-day cycle, midcycle was day 14. The day on which ovulation, judged by oestrogen output, took place was also noted and
1030 RELATION OF OVULATION TO MIDCYCLE IN
45 MENSTRUAL CYCLES to
The day on which ovulation occurred has been shown be variable, ranging from 4 days before to 6 days after
midcycle. The skilled assistance of many technicians, and Mr. H. A. F. Blair, is gratefully acknowledged.
especially
of
REFERENCES
Bell, E. T., Brown, J. B., Fotherby, K., Loraine, J. A. (1962) Lancet, ii, 528. Loraine, J. A. (1965) ibid. i, 403. Brown, J. B. (1955) Biochem. J. 60, 185. (1960) Advanc. clin. Chem. 3, 157. Fotherby, K., Loraine, J. A. (1962) J. Endocrin. 25, 331. Klopper, A., Loraine, J. A. (1958) ibid. 17, 401. Hartman, C. G. (1936) Time of Ovulation in Women. London. Loraine, J. A., Bell, E. T. (1963) Lancet, i, 1340. Harkness, R. A., Mears, E., Jackson, M. C. N. (1963) ibid. ii, -
-
-
—
in the top column of the accompanying table represent the difference between these two dates. Thus " -4 " indicates that ovulation occurred 4 days before midcycle-i.e., on day 10 of a 28-day cycle. Similarly +6 " indicates that ovulation took place 6 days after midcycle-i.e., on day 20 of a 28-day cycle. The results in the three groups of cycles were as follows: Normal subjects receiving no therapy.-In 15 of the 23 cycles the
figures
— —
902.
— — — — — (1965) Acta endocrin., Kbh. (in the press). Speck, G. (1959) Obstet. gynec. Surv. 14, 798. Sturgis, S. H., Pommerenke, W. T. (1950) Fertil. Steril. 1, 113. Torrano, E. F., Murphy, D. P. (1962) ibid. 13, 492.
"
ovulation occurred either at or within 24 hours of midcycle. Of the remaining 8 cycles, ovulation took place from 2 to 4 days before midcycle in 4 and from two to 6 days after midcycle in 4. Subjects receiving long-term treatment with oral contraceptives. -In this group of 12 cycles, ovulation occurred at or within 24 hours of midcycle in 6. In the remainder ovulation was early in 3 and late in 3. Subjects receiving treatment with other compounds.-Of the 10 cycles studied, ovulation occurred at or within 24 hours of midcycle in 5, before midcycle in 4, and after midcycle in 1. Discussion
The results obtained in 23 normal cycles indicate wide variations in the time of ovulation when this time is assessed by urinary oestrogen output and is related to cycle length. The figures indicate that, in normal subjects, ovulation can occur as early as 4 days before and as late as 6 days after midcycle. In the women treated on a longterm basis with progestogen-oestrogen mixtures or on a short-term basis with one of several compounds, the time of ovulation in relation to cycle length is no more variable than in untreated subjects. In 26 of the 45 cycles studied (58%), ovulation occurred within 24 hours of midcycle. In 12 (27%) it actually coincided with the day of midcycle as previously defined, and in the remaining 14 (31%) it took place 24 hours on either side of this day. It was, however, considered justifiable to combine these two groups because of the small errors associated with the calculation of cycle length in days rather than in days and hours, and because the estimation of oestrogens in urine, as opposed to blood, might well reflect physiological processes in the ovary which, owing to the delay associated with the renal handling of the hormones, might have occurred some hours previously. It is of especial interest that, in 11 of the 45 cycles (24%), ovulation took place 2-4 days before midcycle and in 8 (18%) it occurred 2-6 days after midcycle. These results, which indicate the great variability in the time of ovulation from one subject to another, are in keeping with the data of Torrano and Murphy (1962) who studied the incidence of conception following a single artificial insemination in 65 women. The findings in the present investigation suggest that any form of contraception employed, whether by oral progestational agents or by other means, should span a wide area of the cycle.
Summary The time of ovulation, judged by oestrogen excretion in urine, has been related to cycle length in 45 cycles from 31 subjects.
BIOGASTRONE IN INPATIENT TREATMENT OF GASTRIC ULCER A Double-blind
W. R. J. MIDDLETON M.B., B.Sc. (Med.) Sydney REGISTRAR
M.B.
Study
M.B.
A. R. COOKE Sydney, M.R.A.C.P.
RESEARCH FELLOW
D. STEPHEN Sydney, M.C.R.A.,
F.F.R.
DIRECTOR OF RADIOLOGICAL SERVICES
A. P. SKYRING Sydney, M.R.A.C.P.
M.B.
DIRECTOR OF THE A. W. MORROW DEPARTMENT OF GASTROENTEROLOGY
ROYAL PRINCE ALFRED
HOSPITAL, SYDNEY
THE report by Doll et al. (1962) that’Biogastrone’ could influence the rate of radiological healing of gastric ulcers was of considerable interest, for no other substance had previously been shown to exert this effect. Until then only bed rest and avoidance of smoking were known to be of benefit (Doll and Pygott 1952, Doll et al. 1958). The pharmacology of carbenoxolone (of which biogastrone is the disodium salt) has been well studied (Coleman and Parke 1963, Parke et al. 1963). It is a pentacyclic
triterpenoid hydroxyketo-acid: 3-0-(&bgr;-carboxypropionyl)1 l-oxo-18p-olean-12-en-30-oic acid. Doll et al. (1962) reported an average reduction in size of the ulcer of 72% in the biogastrone group compared with only 34% in the control group. Their trial was on radiologically proven gastric ulcers in outpatients with therapy assigned randomly on a double-blind basis. Radiological improvement was assessed after 5 weeks of therapy. In order to observe its effect when added to therapy already conducive to the healing of ulcer, we conducted a trial on inpatients at bed rest. Treatment was given for three weeks so that any added effect of biogastrone might more easily be recognised. Method All patients admitted to Royal Prince Alfred Hospital with a radiologically measurable gastric ulcer crater were considered suitable for the trial. The doctor responsible for the care of each patient could refuse admission to the trial, the usual reasons for exclusion being: (a) admission to hospital specifically for surgery, (b) bleeding or other complications likely to need urgent surgery, and (c) coexistent cardiac failure or hypertension (making undesirable the water and salt retaining effect of biogastrone). Radiological assessment was the only objective measurement made. A barium meal was performed on day 0, and
symptoms. This, however, did not seem to affect the chances of successful resuscitation. In all our patients arterial lactate was increased: levels ranged from 16 mg. per 100 ml. to 130 mg. (normal 8-14 mg.). The size of the increase correlated with the degree of metabolic acidosis indicated by depression of the plasma-bicarbonate. This suggests that the acidosis of cardiac arrest is, in fact, lactic acidosis and that it results from tissue hypoxia. That neither arterial lactate nor bicarbonate correlated with the arterial oxygen saturation is not surprising since cardiac output is the major determinant of tissue oxygenation under these circumstances. There is evidence that metabolic acidosis lowers the threshold for ventricular fibrillation (Gerst et al. 1963), may induce and sustain cardiac asystole (Stewart 1964), and depresses myocardial contractility (Thrower et al. 1961). We have therefore assumed its presence in cardiac arrest and have attempted to correct it as rapidly as possible without waiting for the results of blood analyses. Mellemgaard and Astrup (1960) showed that the dilution space for bicarbonate given rapidly is approximately 30% of the body-weight. If the bicarbonate level at the start of resuscitation is assumed to be about 15 mEq. per litre (fig. 2), the dose (in mEq.) needed to restore it to 25 mEq. per litre can be calculated as 3 x body-weight (kg.). This is the dose we have given initially. If the patient responds and is not hypotensive before its administration is complere it is discontinued and the arterial bicarbonate is then measured. If the patient does not respond the dose is repeated over the next ten to fifteen minutes. This dosage In such a may, on occasion, lead to moderate alkalosis. dangerous situation it is less to be feared than continuing acidosis.
Summary The treatment of 128 patients with cardiac arrest is outlined. 23 survived. Over 3 years 254 patients have been treated and 40 (15-8%) have survived. Metabolic acidosis and raised arterial-lactate levels were found in most patients soon after arrest. Correction of the acidosis with intravenous sodium bicarbonate was found beneficial. Appropriate dosage is
suggested. We are grateful to Dr. M. McGregor and Dr. A. L. Johnson for their encouragement and help with this manuscript. We should also like to thank the nurses of the cardiorespiratory service without whose help this series would not have been possible. This study was aided by grants from the John A. Hartford Foundation. REFERENCES
Astrup, P. (1956) Scand. J. clin. Lab. Invest. 8, 33. Ball, W. C. Jr., Stewart, P. B., Newsham, L. G. S., Bates, D. V. (1962) J. clin. Invest. 41, 519 Baringer, J. R., Salzman, E. W., Jones, W. A., Freidlich, A. L. (1961) New Engl. J. Med. 265, 62. Barker, S. B., Summerson, W. H. (1941) J. biol. Chem. 138, 535. Brown, K. W. G., MacMillan, R. L., Forbath, N., Melgrano, F., Scott, J. W. (1963) Lancet, ii, 349. Clark, D. I. (1962) J. Amer. med. Ass. 181, 337. Gerst, P. H., Fleming, W. H., Malin, J. R. (1963) Physiologist, 6, 185. Himmelhoch, S. R., Dekker, A., Gazzaniga, A. B., Like, A. A. (1964) New Engl. J. Med. 270, 118. Jude, J. B., Kouwenhoven, W. B., Knickerbocker, G. G. (1961) J. Amer. med. Ass. 178, 1063. Klassen, G. A., Broadhurst, C., Peretz, D. I., Johnson, A. L. (1963) Lancet, i, 1290. Lown, B., Amarasingham, R., Neuman, J. (1962) J. Amer. med. Ass. 182, 548. Mellemgaard, K., Astrup, P. (1960) Scand. J. clin. lab. Invest. 12, 187. Robin, E. D., Julian, J. G., Travis, D. M., Crump, C. A. (1959) New Engl. Med. J. 260, 586. Shipman, J. H., McCrady, W., Bradford, A. A. (1962) Amer. J. Cardiol. 10, 551 Stewart, J. S. S. (1964) Brit. med. J. i, 476. Sykes, M. K., Ahmed, N. (1963) Lancet, ii, 347. Thrower, W. B., Darby, T. D., Aldinger, E. E. (1961) Arch. Surg. 82, 56.
TIME OF OVULATION IN RELATION TO CYCLE LENGTH E. T. BELL B.Sc. Durh., Ph.D. Edin. MEMBER OF SCIENTIFIC STAFF
J. A. LORAINE M.B., Ph.D., D.Sc. Edin., F.R.C.P.E. DIRECTOR
MEDICAL RESEARCH COUNCIL CLINICAL ENDOCRINOLOGY
RESEARCH
UNIT,
UNIVERSITY OF EDINBURGH
MANY methods have been described for the determination of ovulation in human subjects (see Hartman 1936, Speck 1959); but in the opinion of Sturgis and Pommerenke (1950), Speck (1959), and others no single test is entirely satisfactory. Hormone-excretion patterns in ovulatory menstrual cycles were reviewed by Loraine and Bell (1963), who emphasised that such cycles were characterised by midcycle and luteal-phase peaks of oestrogen excretion together with a luteal-phase rise in pregnanediol and pregnanetriol output. The peak of oestrogen excretion at midcycle is believed to be closely associated with ovulation itself (Brown 1960), and this peak has been used to determine the day of the cycle on which this event takes place. The aim of the present communication is to attempt to correlate the time of ovulation, judged by the midcycle peak of oestrone and oestradiol output, with the duration of the menstrual cycle. Materials and Methods
Clinical A total of 45 menstrual cycles in 31 women is reported. In all subjects the duration of the cycle was recorded, day 1 being the first day of menstruation. The cycles were subdivided into the following three groups. 1. A series of 23 cycles from 18 normally menstruating women who had received no form of hormonal medication either before or during the investigation. Data derived from some of these cycles have already been published (Brown et al. 1958, Loraine and Bell 1963). 2. A series of 12 cycles in 7 subjects who had previously been treated with various progestogen-oestrogen mixtures as oral contraceptives for periods of time ranging from 9 to 44 calendar months. Details of the subjects studied together with the compounds administered were given by Loraine et al. (1963, 1965). The data reported herein were derived from the first, and in some cases the second, post-treatment cycle. 3. A series of 10 cycles from 6 women who had received treatment for one cycle with one of the following compoundscompound 33,828 (Imperial Chemical Industries Ltd.), norethisterone and its acetate (Schering AG, Berlin), and dydrogesterone (’Duphaston’, Philips Duphar). In the subjects treated with compound 33,828, norethisterone, and norethisterone acetate ovulation was inhibited during drug administration, but with dydrogesterone such an inhibition was unusual (Bell et al. 1962, Brown et al. 1962, Bell and Loraine 1965). The results reported herein are those obtained from the cycles immediately following therapy by the various compounds.
Hormone All the
Assays
collected complete 24-hour urine samples continuously throughout the period of investigation. The excretion of oestradiol, oestrone, and oestriol was measured by the method of Brown (1955) in either 24-hour or 48-hour urine pools. women
Results "
For the purpose of the study " midcycle was defined as the length of the cycle divided by two-e.g., in a 28-day cycle, midcycle was day 14. The day on which ovulation, judged by oestrogen output, took place was also noted and
1030 RELATION OF OVULATION TO MIDCYCLE IN
45 MENSTRUAL CYCLES to
The day on which ovulation occurred has been shown be variable, ranging from 4 days before to 6 days after
midcycle. The skilled assistance of many technicians, and Mr. H. A. F. Blair, is gratefully acknowledged.
especially
of
REFERENCES
Bell, E. T., Brown, J. B., Fotherby, K., Loraine, J. A. (1962) Lancet, ii, 528. Loraine, J. A. (1965) ibid. i, 403. Brown, J. B. (1955) Biochem. J. 60, 185. (1960) Advanc. clin. Chem. 3, 157. Fotherby, K., Loraine, J. A. (1962) J. Endocrin. 25, 331. Klopper, A., Loraine, J. A. (1958) ibid. 17, 401. Hartman, C. G. (1936) Time of Ovulation in Women. London. Loraine, J. A., Bell, E. T. (1963) Lancet, i, 1340. Harkness, R. A., Mears, E., Jackson, M. C. N. (1963) ibid. ii, -
-
-
—
in the top column of the accompanying table represent the difference between these two dates. Thus " -4 " indicates that ovulation occurred 4 days before midcycle-i.e., on day 10 of a 28-day cycle. Similarly +6 " indicates that ovulation took place 6 days after midcycle-i.e., on day 20 of a 28-day cycle. The results in the three groups of cycles were as follows: Normal subjects receiving no therapy.-In 15 of the 23 cycles the
figures
— —
902.
— — — — — (1965) Acta endocrin., Kbh. (in the press). Speck, G. (1959) Obstet. gynec. Surv. 14, 798. Sturgis, S. H., Pommerenke, W. T. (1950) Fertil. Steril. 1, 113. Torrano, E. F., Murphy, D. P. (1962) ibid. 13, 492.
"
ovulation occurred either at or within 24 hours of midcycle. Of the remaining 8 cycles, ovulation took place from 2 to 4 days before midcycle in 4 and from two to 6 days after midcycle in 4. Subjects receiving long-term treatment with oral contraceptives. -In this group of 12 cycles, ovulation occurred at or within 24 hours of midcycle in 6. In the remainder ovulation was early in 3 and late in 3. Subjects receiving treatment with other compounds.-Of the 10 cycles studied, ovulation occurred at or within 24 hours of midcycle in 5, before midcycle in 4, and after midcycle in 1. Discussion
The results obtained in 23 normal cycles indicate wide variations in the time of ovulation when this time is assessed by urinary oestrogen output and is related to cycle length. The figures indicate that, in normal subjects, ovulation can occur as early as 4 days before and as late as 6 days after midcycle. In the women treated on a longterm basis with progestogen-oestrogen mixtures or on a short-term basis with one of several compounds, the time of ovulation in relation to cycle length is no more variable than in untreated subjects. In 26 of the 45 cycles studied (58%), ovulation occurred within 24 hours of midcycle. In 12 (27%) it actually coincided with the day of midcycle as previously defined, and in the remaining 14 (31%) it took place 24 hours on either side of this day. It was, however, considered justifiable to combine these two groups because of the small errors associated with the calculation of cycle length in days rather than in days and hours, and because the estimation of oestrogens in urine, as opposed to blood, might well reflect physiological processes in the ovary which, owing to the delay associated with the renal handling of the hormones, might have occurred some hours previously. It is of especial interest that, in 11 of the 45 cycles (24%), ovulation took place 2-4 days before midcycle and in 8 (18%) it occurred 2-6 days after midcycle. These results, which indicate the great variability in the time of ovulation from one subject to another, are in keeping with the data of Torrano and Murphy (1962) who studied the incidence of conception following a single artificial insemination in 65 women. The findings in the present investigation suggest that any form of contraception employed, whether by oral progestational agents or by other means, should span a wide area of the cycle.
Summary The time of ovulation, judged by oestrogen excretion in urine, has been related to cycle length in 45 cycles from 31 subjects.
BIOGASTRONE IN INPATIENT TREATMENT OF GASTRIC ULCER A Double-blind
W. R. J. MIDDLETON M.B., B.Sc. (Med.) Sydney REGISTRAR
M.B.
Study
M.B.
A. R. COOKE Sydney, M.R.A.C.P.
RESEARCH FELLOW
D. STEPHEN Sydney, M.C.R.A.,
F.F.R.
DIRECTOR OF RADIOLOGICAL SERVICES
A. P. SKYRING Sydney, M.R.A.C.P.
M.B.
DIRECTOR OF THE A. W. MORROW DEPARTMENT OF GASTROENTEROLOGY
ROYAL PRINCE ALFRED
HOSPITAL, SYDNEY
THE report by Doll et al. (1962) that’Biogastrone’ could influence the rate of radiological healing of gastric ulcers was of considerable interest, for no other substance had previously been shown to exert this effect. Until then only bed rest and avoidance of smoking were known to be of benefit (Doll and Pygott 1952, Doll et al. 1958). The pharmacology of carbenoxolone (of which biogastrone is the disodium salt) has been well studied (Coleman and Parke 1963, Parke et al. 1963). It is a pentacyclic
triterpenoid hydroxyketo-acid: 3-0-(&bgr;-carboxypropionyl)1 l-oxo-18p-olean-12-en-30-oic acid. Doll et al. (1962) reported an average reduction in size of the ulcer of 72% in the biogastrone group compared with only 34% in the control group. Their trial was on radiologically proven gastric ulcers in outpatients with therapy assigned randomly on a double-blind basis. Radiological improvement was assessed after 5 weeks of therapy. In order to observe its effect when added to therapy already conducive to the healing of ulcer, we conducted a trial on inpatients at bed rest. Treatment was given for three weeks so that any added effect of biogastrone might more easily be recognised. Method All patients admitted to Royal Prince Alfred Hospital with a radiologically measurable gastric ulcer crater were considered suitable for the trial. The doctor responsible for the care of each patient could refuse admission to the trial, the usual reasons for exclusion being: (a) admission to hospital specifically for surgery, (b) bleeding or other complications likely to need urgent surgery, and (c) coexistent cardiac failure or hypertension (making undesirable the water and salt retaining effect of biogastrone). Radiological assessment was the only objective measurement made. A barium meal was performed on day 0, and