1421 out that " the substance ".
pointed
we
should
Department of Anatomy, University of Leeds, Leeds LS2 9NL.
not
confuse the shadow with
J. A. SHARP.
MASKED PRIMARY (OR TERTIARY) HYPERPARATHYROIDISM
SIR,-Having recently committed the therapeutic solecism of giving vitamin D to a patient from whom a large parathyroid adenoma was later removed, I was interested to read the paper by Professor Dent and his colleagues (May 24, p. 1161) and to find myself in such distinguished company. Now all can be told-and another case
of " masked
and alkaline
phosphatase
55
King-Armstrong units
per 100
ml.).
Plasma-bicarbonate remained low at 18 meq. per I. Although vitamin-D deficiency was not proven it seems very likely that this was present and masked coexistent primary hyperparathyroidism. The possibility of tertiary hyperparathyroidism secondary to Sjogren’s disease and hyperglobulinsemic renal tubular acidosis seems unlikely. The high-normal serum-calcium levels were in retrospect a pointer to the correct diagnosis. As Professor Dent and his colleagues suggest, a short course of vitamin D monitored by blood vitamin-D and calcium levels should confirm the presence of a parathyroid adenoma in these circumstances. Whittington Hospital, Archway Road, London N19.
B. I. HOFFBRAND.
primary (or tertiary) hyperparathyroid-
ism " reported. A 36-year-old vegetarian Kenyan Indian woman was found to be anaemic in November, 1973. Further inquiry revealed general ill health, vague thigh, shoulder, and calf pains, and loss of weight of about 6 kg. during the past year. She had also developed, more recently, nocturia and thirst. Since childhood she had had episodes of painful, bilateral parotid swelling after meals, and said that her four brothers were similarly afflicted. Apart from the anxmia, no abnormalities were found on physical examination. Blood-pressure 110/70 mm. Hg. Investigations.-Hb 9.0 g. per 100 ml., serum-iron 20 !-tg., total iron-binding capacity 405 g. per 100 ml., serum-B12 238 pg, per ml., folate 14-8 ng. per 100 ml. Sternal marrow : iron deficiency only. Serum calcium 10-2 mg. per 100 ml. (sp. gr. 1026), phosphorus 1-5 mg. per 100 ml., alkaline phosphatase 84 King-Armstrong units per 100 ml. (85% bone type), 24-hour urinary calcium 270 mg., phosphorus 450 mg., plasma sodium 139, potassium 4-3, bicarbonate 22, chloride 111 meq. per 1., urea 12 mg. per 100 ml. (repeat bicarbonates 15-20 meq. per 1.). Arterial pH 7-34, Pco. 36 mm. Hg, standard bicarbonate 19meq. per 1., base deficit 6 meq. per I. Lowest urinary pH with ammonium chloride test, 5-05. Maximum urinary osmolality after vasopressin, 606 mosmol per kg. Serum-creatinine 0-7 mg. per 100 ml. Creatinine clearance 83 ml. per min. Skeletal X-rays were considered within normal limits, but in retrospect probably show changes of hyperparathyroidism in hands and spine. Barium meal and follow-through, intravenous pyelogram, and bilateral parotid sialogram were normal. Stools contained no ova, cysts, or occult blood. Serum total-proteins 7-4, albumin 4-5 g. per 100 ml. Increase in gamma-globulin on strip. Rose-Waaler and antinuclear factor negative; gastric parietal cell antibodies positive; E.S.R. 8. No evidence of keratoconjunctivitis sicca on ophthalmological examination (Mr D. A. Langley). Dietary survey indicated deficiency of protein, iron, vitamin D, and vitamin C. Iliac crest biopsy showed poorly calcified fine trabeculae of woven bone in between stouter trabeculae of laminar structure with broad osteoid seams but centrally still well calcified and with no " moth-eaten " lesions. The appearances were considered consistent with a renal osteodystrophy perhaps complicated by dietary deficiency (Dr I. Magrath). A diagnosis of nutritional iron deficiency and osteomalacia with secondary hyperparathyroidism and renal tubular acidosis, with possible Sjogren’s disease, was made. The patient was discharged on ferrous sulphate and calcium-with-vitamin-D tablets, B.P.C. 3 a day. She left for a holiday in Kenya with instructions to have her serum-calcium measured. She was there found to be hypercalcaemic and the vitamin D was stopped. On her return in April, 1974, serum-calcium was 11-0 mg. per 100 ml. She was, however, eeling well, her weight had increased by 7 kg., and her anaamia was corrected. A hydrocortisone test in July, 1974, showed no suppression with serum-calcium levels of around 11 mg. Serum immunoreactive parathyroid hormone in November, 1974, was 3400 pg. per ml. (normal values for this assay < 200 pg. per ml.). In February, 1975, a large (3 x 1-8 x 1-7 cm.) chief-cell parathyroid adenoma was removed. Two other normal parathyroid glands were identified (Mr J. M. Davis). After operation she had prolonged tetany but on May 15, 1975, was well on no medication (serum calcium 87, phosphorus 3-5,
MEDICAL CARE OF CHILDHOOD LEUKÆMIA
SIR,-One may applaud Dr McCarthy’s intentions (May 17, p. 1128), and I appreciate that his article is an abbreviated form of his thesis, but the conclusions should not be allowed to pass without comment. " The survival of children given optimal regimens at local hospitals was equivalent to that of two of the three special centres. It is concluded that a regional policy for childhood leukaemia should be concerned to improve treatment regimens at local hospitals rather than an attempt to concentrate care at a few centres." That really will not do. For one thing, the figures, small as they are, still favour the two special centres against the better general hospital (7/10 survivors compared with 6/14), and it quite ignores the best results of all from the other special centre (16/17 survivors). An unprejudiced reader, on learning that " assessment of social, psychological, satisfaction or cost outcomes showed no difference between the groups " could only conclude that special centres should be preferred since they achieved better results irrespective of regimen. Such a conclusion is not surprising, since current chemotherapy, poised, as it must be, between hazardous overdosage and ineffective underdosage, must be managed by those with the greatest experience. Of course, in some circumstances treatment at a special centre may be contraindicated, and, as experience is disseminated, there will be more hospitals with the requisite fund of expertise. A.L.L. is in any case a diverse disease and many considerations must be balanced before the decision is taken as to how and where a child should be treated. Eventually, when there exists a relatively safe but curative treatment for most patients, a general policy of decentralisation could be recommended. But that is not yet the situation, and it would be tragic if the improved results now possible were to encourage the premature dissolution of the centres on which success still largely depends. Royal Marsden Hospital, H. E. M. KAY, Fulham Road, London SW3 6JJ. Secretary, M.R.C. Leukæmia Committee.
SiR,—In the currency of the medical oncologist or haematologist, lymphoblastic leukaemia ranks with diamonds. It does not surprise me that many practitioners wish to assemble patients with this condition. They provide an opportunity to test one’s skills and resources as few other haematological disorders, with the possibility of steering a patient out of hazard into cure. I think the claim by Dr McCarthy (May 17, p. 1128) that " treatment is moving towards semi-routine regimes " refers to the " protocol-bound " approach to therapy, essentially unimaginative and unamenable to adaptation. I agree with Professor Hardisty (May 31, p. 1235) that this is a disconcerting observation with echoes of complacency
1422 It is also difficult to understand Dr McCarthy’s claim that the outlook in lymphoblastic leukaemia is as good after management at district hospitals as at the special centres that he has investigated. The figures which he provides contradict this conclusion: at the district hospitals 19 out of 25 patients had died within three years of diagnosis; after treatment at the special centres, 4 out of 27 had died within a similar time. There are, of course, important considerations in addition to survival, but without survival they become immaterial. Working at a district general hospital, in the proximity of a special centre, I would have a vested interest in Dr McCarthy’s conclusions-but his argument doesn’t add up. St. George’s Hospital, Blackshaw Road, London SW17 0QT.
MICHAEL S. ROSE.
*** This letter has been shown whose reply follows.-ED. L.
to
Dr
McCarthy,
SiR,-The comparison in my study to which I drew was between two special centres and those district hospitals that had used comparable treatment regimens. The latter group included several London undergraduate teaching hospitals. The study was limited in size because attention
interviews were needed to measure other outcomes; strict statistical analysis did not therefore seem appropriate. I wished to emphasise that a regional organisational policy based on consensus between all clinicians looking after children with leukxmia would particularly benefit those at present with short survival. Data routinely collected in this way, linking treatment and outcomes on a population basis, would allow far better resolution of the site-of-care question I raised. Hammersmith Hospital, Du Cane Road, London W12 OHS.
or
Watkin’s letter that there is Ministry of
no
risk.
Agriculture, Fisheries, and Food, Fisheries Laboratory, Burnham-on-Crouch.
Public Health Laboratory, Royal Cornwall Hospital (City), Truro TR1 2HZ.
P. C. WOOD.
G. I. BARROW.
IMPROVING THE BIOAVAILABILITY OF DIGOXIN
SiR,-Therapeutic blood-levels of digoxin after oral administration of the drug are dependent on the content of digoxin in the tablet and an adequate rate of dissolution 1-5 (a dissolution-rate in an acid medium of over 70% per hour being satisfactory 2). A solution of digoxin (’ Lanoxin’ elixir) is absorbed better than digoxin in tablet form,3 but lately we have had the opportunity of studying the absorption of a capsule preparation (’ Lanoxicap’) of digoxin and we report our initial results and impressions below. Six healthy volunteers, aged 26 to 42 years, with normal creatinine clearances underwent study on five separate occasions, each separated by at least 2 weeks. The single-dose treatments ABSORPTION OF DIFFERENT DIGOIXN PREPARATIONS
MARK MCCARTHY.
FISH AND SHELLFISH HYGIENE SIR,-Following your editorial (May 3, p. 1020) on the recent W.H.O. report,1 we read with interest the letter by Dr Simmons and Mr Watkin (May 24, p. 1185). We agree with the sentiments expressed on consumer protection, and we are glad to note that every source of supply is investigated-both bacteriologically and through inquiries to local public-health authorities-by the Fishmongers’ Company. However, about 100 samples a year does not seem many in relation either to the number of producers in the U.K. or to the large market trade. It should be noted that samples of shellfish taken at source by some local authorities are also examined bacteriologically by publichealth or other laboratories, not only at the beginning of each season, but on a continuing basis. We consider these practices essential for effective control. We note that Vibrio parahaemolyticus was not found in imported shrimps and prawns examined by the Fishmongers’ Company, although it has often been isolated from other samples of supplies entering the country. Indeed, imported cooked and peeled prawns have lately been responsible for at least one outbreak of food-poisoning caused by this organism. Vibrio parahamolyticus has also been isolated from British sources,2 including shellfish, sea water, and sediments. Furthermore, it has caused an outbreak of food-poisoning associated with indigenous crabmeat.33 A number of laboratories are therefore collaborating with us in a survey of its distribution in British
coastal waters. We do not wish
parahaemolyticus are great, either from home-profrom imported marine products, but equally we cannot accept the implication in Dr Simmons’ and Mr Vibrio duced
*
Results extrapolated from previous experiments of subjects are shown in parentheses.
suggest that health hazards from
1. Fish and Shellfish Hygiene. W.H.O. techn. Rep. Ser. 1974, no. 550. 2. Barrow, G. I., Miller, D. C. Lancet, 1972, i, 485. 3. Hooper, W. L., Barrow, G. I., McNab, D. J. N. ibid. 1974, i, 1100.
larger group
administered according to a balanced, incomplete block design and consisted of five out of six schedules: (a) eight capsules containing 0-05 mg. digoxin each; (b) four capsules each containing 0-10 mg.; (c) two capsules containing 0-30 mg.; (d) an intravenous infusion given over 1 hour containing 0-40 mg. injectable digoxin in 250 ml. 5% dextrose in water; (e) two reference digoxin tablets of 0-20 mg. each; and (f) digoxin (lanoxin) solution containing 0-40 mg. Digoxin was administered after an overnight fast; capsules and tablets were swallowed with 250 ml. water and the digoxin solution was added to 200 ml. water containing 3 ml. ethyl alcohol and rinsed with 50 ml. water. Venous blood-samples were taken at 0, to 1, 1, 2, 3, 4, and 6 hours, and the serum analysed in duplicate on two separate occasions, with separate calibration curves prepared from serum from the subject being
were
studied.
All
samples have not yet been analysed, but certain interesting features are obvious. The areas under concentration-time curves (ng./ml. per hour) were measured by planimetry. Three of the subjects were included in a previous study of the absorption of tablet digoxin (0’5 mg.)2 and the results were extrapolated to make them comparable (see accompanying table). Lindenbaum, J., Butler, V. P., Murphy, J. E., Cresswell, R. M. Lancet, 1973, i, 1215. 2. Binnion, P F. Clin. Pharmac. Ther. 1974, 16, 807. 3. Johnson, B. F., Bye, C. Br. Heart J. 1975, 37, 203. 4. Wagner, J. G. Am. Heart J. 1974, 88, 133. 5. Dunning, A. J. Eur. J. Cardiol. 1974, 2, 1. 1.
to
on a
pointed
we
should
Department of Anatomy, University of Leeds, Leeds LS2 9NL.
not
confuse the shadow with
J. A. SHARP.
MASKED PRIMARY (OR TERTIARY) HYPERPARATHYROIDISM
SIR,-Having recently committed the therapeutic solecism of giving vitamin D to a patient from whom a large parathyroid adenoma was later removed, I was interested to read the paper by Professor Dent and his colleagues (May 24, p. 1161) and to find myself in such distinguished company. Now all can be told-and another case
of " masked
and alkaline
phosphatase
55
King-Armstrong units
per 100
ml.).
Plasma-bicarbonate remained low at 18 meq. per I. Although vitamin-D deficiency was not proven it seems very likely that this was present and masked coexistent primary hyperparathyroidism. The possibility of tertiary hyperparathyroidism secondary to Sjogren’s disease and hyperglobulinsemic renal tubular acidosis seems unlikely. The high-normal serum-calcium levels were in retrospect a pointer to the correct diagnosis. As Professor Dent and his colleagues suggest, a short course of vitamin D monitored by blood vitamin-D and calcium levels should confirm the presence of a parathyroid adenoma in these circumstances. Whittington Hospital, Archway Road, London N19.
B. I. HOFFBRAND.
primary (or tertiary) hyperparathyroid-
ism " reported. A 36-year-old vegetarian Kenyan Indian woman was found to be anaemic in November, 1973. Further inquiry revealed general ill health, vague thigh, shoulder, and calf pains, and loss of weight of about 6 kg. during the past year. She had also developed, more recently, nocturia and thirst. Since childhood she had had episodes of painful, bilateral parotid swelling after meals, and said that her four brothers were similarly afflicted. Apart from the anxmia, no abnormalities were found on physical examination. Blood-pressure 110/70 mm. Hg. Investigations.-Hb 9.0 g. per 100 ml., serum-iron 20 !-tg., total iron-binding capacity 405 g. per 100 ml., serum-B12 238 pg, per ml., folate 14-8 ng. per 100 ml. Sternal marrow : iron deficiency only. Serum calcium 10-2 mg. per 100 ml. (sp. gr. 1026), phosphorus 1-5 mg. per 100 ml., alkaline phosphatase 84 King-Armstrong units per 100 ml. (85% bone type), 24-hour urinary calcium 270 mg., phosphorus 450 mg., plasma sodium 139, potassium 4-3, bicarbonate 22, chloride 111 meq. per 1., urea 12 mg. per 100 ml. (repeat bicarbonates 15-20 meq. per 1.). Arterial pH 7-34, Pco. 36 mm. Hg, standard bicarbonate 19meq. per 1., base deficit 6 meq. per I. Lowest urinary pH with ammonium chloride test, 5-05. Maximum urinary osmolality after vasopressin, 606 mosmol per kg. Serum-creatinine 0-7 mg. per 100 ml. Creatinine clearance 83 ml. per min. Skeletal X-rays were considered within normal limits, but in retrospect probably show changes of hyperparathyroidism in hands and spine. Barium meal and follow-through, intravenous pyelogram, and bilateral parotid sialogram were normal. Stools contained no ova, cysts, or occult blood. Serum total-proteins 7-4, albumin 4-5 g. per 100 ml. Increase in gamma-globulin on strip. Rose-Waaler and antinuclear factor negative; gastric parietal cell antibodies positive; E.S.R. 8. No evidence of keratoconjunctivitis sicca on ophthalmological examination (Mr D. A. Langley). Dietary survey indicated deficiency of protein, iron, vitamin D, and vitamin C. Iliac crest biopsy showed poorly calcified fine trabeculae of woven bone in between stouter trabeculae of laminar structure with broad osteoid seams but centrally still well calcified and with no " moth-eaten " lesions. The appearances were considered consistent with a renal osteodystrophy perhaps complicated by dietary deficiency (Dr I. Magrath). A diagnosis of nutritional iron deficiency and osteomalacia with secondary hyperparathyroidism and renal tubular acidosis, with possible Sjogren’s disease, was made. The patient was discharged on ferrous sulphate and calcium-with-vitamin-D tablets, B.P.C. 3 a day. She left for a holiday in Kenya with instructions to have her serum-calcium measured. She was there found to be hypercalcaemic and the vitamin D was stopped. On her return in April, 1974, serum-calcium was 11-0 mg. per 100 ml. She was, however, eeling well, her weight had increased by 7 kg., and her anaamia was corrected. A hydrocortisone test in July, 1974, showed no suppression with serum-calcium levels of around 11 mg. Serum immunoreactive parathyroid hormone in November, 1974, was 3400 pg. per ml. (normal values for this assay < 200 pg. per ml.). In February, 1975, a large (3 x 1-8 x 1-7 cm.) chief-cell parathyroid adenoma was removed. Two other normal parathyroid glands were identified (Mr J. M. Davis). After operation she had prolonged tetany but on May 15, 1975, was well on no medication (serum calcium 87, phosphorus 3-5,
MEDICAL CARE OF CHILDHOOD LEUKÆMIA
SIR,-One may applaud Dr McCarthy’s intentions (May 17, p. 1128), and I appreciate that his article is an abbreviated form of his thesis, but the conclusions should not be allowed to pass without comment. " The survival of children given optimal regimens at local hospitals was equivalent to that of two of the three special centres. It is concluded that a regional policy for childhood leukaemia should be concerned to improve treatment regimens at local hospitals rather than an attempt to concentrate care at a few centres." That really will not do. For one thing, the figures, small as they are, still favour the two special centres against the better general hospital (7/10 survivors compared with 6/14), and it quite ignores the best results of all from the other special centre (16/17 survivors). An unprejudiced reader, on learning that " assessment of social, psychological, satisfaction or cost outcomes showed no difference between the groups " could only conclude that special centres should be preferred since they achieved better results irrespective of regimen. Such a conclusion is not surprising, since current chemotherapy, poised, as it must be, between hazardous overdosage and ineffective underdosage, must be managed by those with the greatest experience. Of course, in some circumstances treatment at a special centre may be contraindicated, and, as experience is disseminated, there will be more hospitals with the requisite fund of expertise. A.L.L. is in any case a diverse disease and many considerations must be balanced before the decision is taken as to how and where a child should be treated. Eventually, when there exists a relatively safe but curative treatment for most patients, a general policy of decentralisation could be recommended. But that is not yet the situation, and it would be tragic if the improved results now possible were to encourage the premature dissolution of the centres on which success still largely depends. Royal Marsden Hospital, H. E. M. KAY, Fulham Road, London SW3 6JJ. Secretary, M.R.C. Leukæmia Committee.
SiR,—In the currency of the medical oncologist or haematologist, lymphoblastic leukaemia ranks with diamonds. It does not surprise me that many practitioners wish to assemble patients with this condition. They provide an opportunity to test one’s skills and resources as few other haematological disorders, with the possibility of steering a patient out of hazard into cure. I think the claim by Dr McCarthy (May 17, p. 1128) that " treatment is moving towards semi-routine regimes " refers to the " protocol-bound " approach to therapy, essentially unimaginative and unamenable to adaptation. I agree with Professor Hardisty (May 31, p. 1235) that this is a disconcerting observation with echoes of complacency
1422 It is also difficult to understand Dr McCarthy’s claim that the outlook in lymphoblastic leukaemia is as good after management at district hospitals as at the special centres that he has investigated. The figures which he provides contradict this conclusion: at the district hospitals 19 out of 25 patients had died within three years of diagnosis; after treatment at the special centres, 4 out of 27 had died within a similar time. There are, of course, important considerations in addition to survival, but without survival they become immaterial. Working at a district general hospital, in the proximity of a special centre, I would have a vested interest in Dr McCarthy’s conclusions-but his argument doesn’t add up. St. George’s Hospital, Blackshaw Road, London SW17 0QT.
MICHAEL S. ROSE.
*** This letter has been shown whose reply follows.-ED. L.
to
Dr
McCarthy,
SiR,-The comparison in my study to which I drew was between two special centres and those district hospitals that had used comparable treatment regimens. The latter group included several London undergraduate teaching hospitals. The study was limited in size because attention
interviews were needed to measure other outcomes; strict statistical analysis did not therefore seem appropriate. I wished to emphasise that a regional organisational policy based on consensus between all clinicians looking after children with leukxmia would particularly benefit those at present with short survival. Data routinely collected in this way, linking treatment and outcomes on a population basis, would allow far better resolution of the site-of-care question I raised. Hammersmith Hospital, Du Cane Road, London W12 OHS.
or
Watkin’s letter that there is Ministry of
no
risk.
Agriculture, Fisheries, and Food, Fisheries Laboratory, Burnham-on-Crouch.
Public Health Laboratory, Royal Cornwall Hospital (City), Truro TR1 2HZ.
P. C. WOOD.
G. I. BARROW.
IMPROVING THE BIOAVAILABILITY OF DIGOXIN
SiR,-Therapeutic blood-levels of digoxin after oral administration of the drug are dependent on the content of digoxin in the tablet and an adequate rate of dissolution 1-5 (a dissolution-rate in an acid medium of over 70% per hour being satisfactory 2). A solution of digoxin (’ Lanoxin’ elixir) is absorbed better than digoxin in tablet form,3 but lately we have had the opportunity of studying the absorption of a capsule preparation (’ Lanoxicap’) of digoxin and we report our initial results and impressions below. Six healthy volunteers, aged 26 to 42 years, with normal creatinine clearances underwent study on five separate occasions, each separated by at least 2 weeks. The single-dose treatments ABSORPTION OF DIFFERENT DIGOIXN PREPARATIONS
MARK MCCARTHY.
FISH AND SHELLFISH HYGIENE SIR,-Following your editorial (May 3, p. 1020) on the recent W.H.O. report,1 we read with interest the letter by Dr Simmons and Mr Watkin (May 24, p. 1185). We agree with the sentiments expressed on consumer protection, and we are glad to note that every source of supply is investigated-both bacteriologically and through inquiries to local public-health authorities-by the Fishmongers’ Company. However, about 100 samples a year does not seem many in relation either to the number of producers in the U.K. or to the large market trade. It should be noted that samples of shellfish taken at source by some local authorities are also examined bacteriologically by publichealth or other laboratories, not only at the beginning of each season, but on a continuing basis. We consider these practices essential for effective control. We note that Vibrio parahaemolyticus was not found in imported shrimps and prawns examined by the Fishmongers’ Company, although it has often been isolated from other samples of supplies entering the country. Indeed, imported cooked and peeled prawns have lately been responsible for at least one outbreak of food-poisoning caused by this organism. Vibrio parahamolyticus has also been isolated from British sources,2 including shellfish, sea water, and sediments. Furthermore, it has caused an outbreak of food-poisoning associated with indigenous crabmeat.33 A number of laboratories are therefore collaborating with us in a survey of its distribution in British
coastal waters. We do not wish
parahaemolyticus are great, either from home-profrom imported marine products, but equally we cannot accept the implication in Dr Simmons’ and Mr Vibrio duced
*
Results extrapolated from previous experiments of subjects are shown in parentheses.
suggest that health hazards from
1. Fish and Shellfish Hygiene. W.H.O. techn. Rep. Ser. 1974, no. 550. 2. Barrow, G. I., Miller, D. C. Lancet, 1972, i, 485. 3. Hooper, W. L., Barrow, G. I., McNab, D. J. N. ibid. 1974, i, 1100.
larger group
administered according to a balanced, incomplete block design and consisted of five out of six schedules: (a) eight capsules containing 0-05 mg. digoxin each; (b) four capsules each containing 0-10 mg.; (c) two capsules containing 0-30 mg.; (d) an intravenous infusion given over 1 hour containing 0-40 mg. injectable digoxin in 250 ml. 5% dextrose in water; (e) two reference digoxin tablets of 0-20 mg. each; and (f) digoxin (lanoxin) solution containing 0-40 mg. Digoxin was administered after an overnight fast; capsules and tablets were swallowed with 250 ml. water and the digoxin solution was added to 200 ml. water containing 3 ml. ethyl alcohol and rinsed with 50 ml. water. Venous blood-samples were taken at 0, to 1, 1, 2, 3, 4, and 6 hours, and the serum analysed in duplicate on two separate occasions, with separate calibration curves prepared from serum from the subject being
were
studied.
All
samples have not yet been analysed, but certain interesting features are obvious. The areas under concentration-time curves (ng./ml. per hour) were measured by planimetry. Three of the subjects were included in a previous study of the absorption of tablet digoxin (0’5 mg.)2 and the results were extrapolated to make them comparable (see accompanying table). Lindenbaum, J., Butler, V. P., Murphy, J. E., Cresswell, R. M. Lancet, 1973, i, 1215. 2. Binnion, P F. Clin. Pharmac. Ther. 1974, 16, 807. 3. Johnson, B. F., Bye, C. Br. Heart J. 1975, 37, 203. 4. Wagner, J. G. Am. Heart J. 1974, 88, 133. 5. Dunning, A. J. Eur. J. Cardiol. 1974, 2, 1. 1.
to
on a
