691 ing of 90 mg/dl on the Ames reflectance meter. (A 5 mmo)/l solution gives a reading of 200-250 mg/dl). If the test colour does not reach that of the 90 mg/dl block on the side of the bottle then the dextrostix are failing and that bottle must be discarded.
coffee/day in man." If the average weight of a man is assumed to be 70 kg, equivalent dosage of caffeine in man would amount to 6.3 g. Since the caffeine content of a 6 oz cup of ground roast coffee has been found to average 85 mg (6--8 cups=510-680 mg) based on analysis of more than 2000 samples of nearly thirty coffee products,’ it would appear that
Middlesex Hospital Medical Astor College, London W1
either the Rhode Island rats were fed a very strong cup of coffee or that an error was made in extrapolation.
School,
J. R. STRADLINC
Coffee Information Institute, New York, N.Y. 10017, U.S.A.
KENNETH N. ANDERSON
BLOOD-SAMPLING AND DIABETIC CONTROL
Sttt,-Dr Johnson (Sept. 18, p. 631) makes certain assumptions which are theoretically admirable but less fine in practical terms for the patient. The purpose of control may be "the continuous maintenance of blood-glucose levels as near as possible to those in non-diabetics", but in practice for many insulin-dependent diabetics this "normalisation" of bloodglucose levels is achieved only for a relatively short period before the next meal or before an episode of hypoglycsemia. Why test an early-morning specimen of urine, asks Dr Johnson? Surely, to avoid such hypoglycaemia through too high a dose of a long-acting insulin (e.g., protamine zinc) or soluble insulin given later in the preceding day. In addition, many diabetics test their urine just before retiring for the night, a sensible precaution since a near-normal sugar-free result at that time may well indicate the need to ingest some additional
carbohydrate turnal
preventive
as a
measure
hypoglycsemia.
against possible
noc-
***This letter has been shown to Dr Rotenberg and his colleagues, whose reply follows.-ED. L. SIR,-Rats metabolise many drugs
more quickly than does A common conversion used in toxicology is that the rat is one tenth as sensitive to toxic effects of drugs, on a per kilogram basis, as is man. The lethal dose of caffeine in man has been estimated to be 10 g2 or, assuming a weight of 70 kg, 143 mg/kg. The L.D. of caffeine in rat is 330 mg/kg,3 or approximately 2-3 times greater than man. Using the 10-fold difference in sensitivity, 90 mg/kg in rat would be roughly man.
equivalent to 630 mg caffeine in man (i.e., 6-8 cups of coffee). Alternatively, if the rat is only 2.3times as sensitive to caffeine’s toxic effect as is man, then the 90 mg/kg dose we administered to the rat is equivalent to 2700 mg in man, or approximately that found in 27-32 cups of coffee.
A common error prevalent in diabetic clinics is the assumption that a patient’s insulin requirements are the same from day to day. Variation in physical activity, mental stress, insulin-antibody production, and so on contribute to produce day-to-day variations in control. In practice the insulin dosage administered is a compromise between such extremes. At weekends the differences in activity from weekday work may well necessitate a temporary alteration in dosage or diet. To suggest that patients make three visits to the clinic in one day for blood-sugar tests or one visit after different meals on three separate days is expecting rather more from the generally uncomplaining patient, than, I suspect, he is
Department of Pharmacology and Toxicology, University of Rhode Island Kingston, Rhode Island. 02881, U.S.A.
prepared to give. What guarantee is there that the blood-sugar curves suggested have any relevance to values pertaining weeks or months later at the time of the patient’s next clinical attendance? Most clinics nowadays assess state of control from blood-sugar results provided only minutes after the blood has been withdrawn from the patient. So please let us have no more talk of extra visits to the clinic, extra blood-samples, and so on. Both as a diabetic of twenty years’ duration and as a clinical biochemist in an endocrine department, I admit I am biased. Dr Johnson tells us that "once the importance of good diabetic control has been explained to the patients control of the diabetes becomes more efficient" (presumbly for the less complex cases If only diabetics could respond biochemically in this ’.B3B’ to such encouraging advice. However, as any biochemist knows, we are all different, all individual. There are no truly "normal" people. Why then suppose there are any normal
timolol
...
diabetics ? Endocrine Department,
Hospital for Women,
Chelsea
London SW3
A. C. LOVESEY
CAFFEINE IN COFFEE
SIR,-The letter by ;’:p.141) includes :.’roneous. ..’.
Rotenberg
and his
colleagues (July
extrapolation of data that
may be discuss a caffeine dosage of "90 mg/kg/day" "dose approximately equal to 6-8 cups of
They
rats as a
Dr an
FRED A. ROTENBERG JOHN J. DE FEO ALVIN K. SWONGER
TIMOLOL, HYDROCHLOROTMAZIDE, BLOOD-PRESSURE, AND RENIN IN ESSENTIA] HYPERTENSION
SiR,—Professor Chalmers and his colleagues (Aug. 14, 328) reported an additive antihypertensive effect of combined treatment with timolol (30 mg/day) and hydrochlorothiazide (50 mg/day). They considered the antihypertensive effect of p.
be independent of changes in plasma-renin-activity Bravo et a14 added propranolol to long-term diuretic (P.R.A.). treatment in patients with essential hypertension and arrived at a similar conclusion: "effects of p-adrenergic blockade on renin activity and on arterial pressure seem to be two separate phenomena that are not directly linked together." We have used a combined treatment of timolol (30 mg/day) and a saliuretic drug for nine months in 25 patients with W.H.O. grade i-ti essential hypertension who were considered to have responded poorly to saliuretic drugs alone.The study originally consisted of 55 patients: 16 responded to saliuretics and continued this therapy for an additional nine months, and 4 patients did not complete the study. Our data confirm those of Chalmers et al. We found no correlation between saliuretic-stimulated P.R.A. and blood-pressure reduction during timolol/diuretic combination. Addition of timolol to the treatment with diuretic drugs caused an additional fall of blood-pressure which was not related to individual changes of P.R.A. during this treatment. In fact, 2 patients showed a rise in P.R.A. despite the addition of timolol and yet their blood-pressures responded favourably. There was no significant difference in P.R.A. between the 16 patients responding well to saliuretics alone and the 25 poor responders when comto
1. Burg, A. Tea Coffee Trade J. January, 1975. 2. Goodman, L. S, Gilman, A. (editors) The Pharmacological Basis of Therapeutics, New York, 1975. 3. Casida, J. E. (editor) Pyrethrum: the Natural Insecticide. New York, 1973. 4. Bravo, E. L., Tarazi, R. C., Dustan, H. P. New Engl. J. Med. 1975, 292, 66.
5
Kurppa, K., Kannas, M., Fyhrquist, F. Excerpta med. (in the press).
coffee/day in man." If the average weight of a man is assumed to be 70 kg, equivalent dosage of caffeine in man would amount to 6.3 g. Since the caffeine content of a 6 oz cup of ground roast coffee has been found to average 85 mg (6--8 cups=510-680 mg) based on analysis of more than 2000 samples of nearly thirty coffee products,’ it would appear that
Middlesex Hospital Medical Astor College, London W1
either the Rhode Island rats were fed a very strong cup of coffee or that an error was made in extrapolation.
School,
J. R. STRADLINC
Coffee Information Institute, New York, N.Y. 10017, U.S.A.
KENNETH N. ANDERSON
BLOOD-SAMPLING AND DIABETIC CONTROL
Sttt,-Dr Johnson (Sept. 18, p. 631) makes certain assumptions which are theoretically admirable but less fine in practical terms for the patient. The purpose of control may be "the continuous maintenance of blood-glucose levels as near as possible to those in non-diabetics", but in practice for many insulin-dependent diabetics this "normalisation" of bloodglucose levels is achieved only for a relatively short period before the next meal or before an episode of hypoglycsemia. Why test an early-morning specimen of urine, asks Dr Johnson? Surely, to avoid such hypoglycaemia through too high a dose of a long-acting insulin (e.g., protamine zinc) or soluble insulin given later in the preceding day. In addition, many diabetics test their urine just before retiring for the night, a sensible precaution since a near-normal sugar-free result at that time may well indicate the need to ingest some additional
carbohydrate turnal
preventive
as a
measure
hypoglycsemia.
against possible
noc-
***This letter has been shown to Dr Rotenberg and his colleagues, whose reply follows.-ED. L. SIR,-Rats metabolise many drugs
more quickly than does A common conversion used in toxicology is that the rat is one tenth as sensitive to toxic effects of drugs, on a per kilogram basis, as is man. The lethal dose of caffeine in man has been estimated to be 10 g2 or, assuming a weight of 70 kg, 143 mg/kg. The L.D. of caffeine in rat is 330 mg/kg,3 or approximately 2-3 times greater than man. Using the 10-fold difference in sensitivity, 90 mg/kg in rat would be roughly man.
equivalent to 630 mg caffeine in man (i.e., 6-8 cups of coffee). Alternatively, if the rat is only 2.3times as sensitive to caffeine’s toxic effect as is man, then the 90 mg/kg dose we administered to the rat is equivalent to 2700 mg in man, or approximately that found in 27-32 cups of coffee.
A common error prevalent in diabetic clinics is the assumption that a patient’s insulin requirements are the same from day to day. Variation in physical activity, mental stress, insulin-antibody production, and so on contribute to produce day-to-day variations in control. In practice the insulin dosage administered is a compromise between such extremes. At weekends the differences in activity from weekday work may well necessitate a temporary alteration in dosage or diet. To suggest that patients make three visits to the clinic in one day for blood-sugar tests or one visit after different meals on three separate days is expecting rather more from the generally uncomplaining patient, than, I suspect, he is
Department of Pharmacology and Toxicology, University of Rhode Island Kingston, Rhode Island. 02881, U.S.A.
prepared to give. What guarantee is there that the blood-sugar curves suggested have any relevance to values pertaining weeks or months later at the time of the patient’s next clinical attendance? Most clinics nowadays assess state of control from blood-sugar results provided only minutes after the blood has been withdrawn from the patient. So please let us have no more talk of extra visits to the clinic, extra blood-samples, and so on. Both as a diabetic of twenty years’ duration and as a clinical biochemist in an endocrine department, I admit I am biased. Dr Johnson tells us that "once the importance of good diabetic control has been explained to the patients control of the diabetes becomes more efficient" (presumbly for the less complex cases If only diabetics could respond biochemically in this ’.B3B’ to such encouraging advice. However, as any biochemist knows, we are all different, all individual. There are no truly "normal" people. Why then suppose there are any normal
timolol
...
diabetics ? Endocrine Department,
Hospital for Women,
Chelsea
London SW3
A. C. LOVESEY
CAFFEINE IN COFFEE
SIR,-The letter by ;’:p.141) includes :.’roneous. ..’.
Rotenberg
and his
colleagues (July
extrapolation of data that
may be discuss a caffeine dosage of "90 mg/kg/day" "dose approximately equal to 6-8 cups of
They
rats as a
Dr an
FRED A. ROTENBERG JOHN J. DE FEO ALVIN K. SWONGER
TIMOLOL, HYDROCHLOROTMAZIDE, BLOOD-PRESSURE, AND RENIN IN ESSENTIA] HYPERTENSION
SiR,—Professor Chalmers and his colleagues (Aug. 14, 328) reported an additive antihypertensive effect of combined treatment with timolol (30 mg/day) and hydrochlorothiazide (50 mg/day). They considered the antihypertensive effect of p.
be independent of changes in plasma-renin-activity Bravo et a14 added propranolol to long-term diuretic (P.R.A.). treatment in patients with essential hypertension and arrived at a similar conclusion: "effects of p-adrenergic blockade on renin activity and on arterial pressure seem to be two separate phenomena that are not directly linked together." We have used a combined treatment of timolol (30 mg/day) and a saliuretic drug for nine months in 25 patients with W.H.O. grade i-ti essential hypertension who were considered to have responded poorly to saliuretic drugs alone.The study originally consisted of 55 patients: 16 responded to saliuretics and continued this therapy for an additional nine months, and 4 patients did not complete the study. Our data confirm those of Chalmers et al. We found no correlation between saliuretic-stimulated P.R.A. and blood-pressure reduction during timolol/diuretic combination. Addition of timolol to the treatment with diuretic drugs caused an additional fall of blood-pressure which was not related to individual changes of P.R.A. during this treatment. In fact, 2 patients showed a rise in P.R.A. despite the addition of timolol and yet their blood-pressures responded favourably. There was no significant difference in P.R.A. between the 16 patients responding well to saliuretics alone and the 25 poor responders when comto
1. Burg, A. Tea Coffee Trade J. January, 1975. 2. Goodman, L. S, Gilman, A. (editors) The Pharmacological Basis of Therapeutics, New York, 1975. 3. Casida, J. E. (editor) Pyrethrum: the Natural Insecticide. New York, 1973. 4. Bravo, E. L., Tarazi, R. C., Dustan, H. P. New Engl. J. Med. 1975, 292, 66.
5
Kurppa, K., Kannas, M., Fyhrquist, F. Excerpta med. (in the press).
