- Email: [email protected]
GALACTOSE AND OVARIAN CANCER
452
lormetazepam-takers. van der Kroefs observations about derealisation, panics, development of paranoid ideas, loss of weight and personality changes were also confirmed. 12 Upjohn-funded research has concentrated on dosing for 1-7 nights: little time for the development of tolerance. It is with regular intake of triazolam that brain function gradually changes and leads to daytime anxiety, while in the sleep laboratory the response of the brain after 3 weeks differs from the response to the first 2 doses.l3 To return to the 0 25 mg dosage: Bixler et al have reviewed the spontaneous adverse reports to the US Food and Drug Administration for triazolam, temazepam, and flurazepam and found a differential pattern. Daytime sedation was noted with all three, but triazolam caused agitation, hallucinations, and amnesia, not just with the 0-5 mg dose but frequently with the 0-25 mg dose too.14 van der Kroef was right, you were right to publish his letter in 1979, and the Netherlands have been right to ban triazolam since. People who complain of poor sleep are generally anxious people. If after 3 weeks they are even more anxious, doctor and patient alike easily attribute any change to the patient rather than to the drug. It is a matter for concern that halcion was marketed on the basis of deficient research. It should no longer be sold. University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh EH10 5HF
IAN OSWALD
1. van der Kroef C. Reactions to triazolam. Lancet 1979; ii: 526. 2. Barclay WR, Ayd FJ Jr, Callan JP, et al. Behavioural reactions to triazolam. Lancet
1979; ii: 1018. 3. MacLeod N, Kratochvil CH. Behavioural reactions to triazolam. Lancet 1979; ii: 638. 4. Lasagna L. The Halcion story: trial by media. Lancet 1980; i: 815. 5. Baker MI, Oleen MA. The use of benzodiazepine hypnotics in the elderly. Pharmacotherapy 1988; 8: 241-47. 6. Reeves RL. Comparison of triazolam, flurazepam, and placebo as hypnotics in geriatric patients with insomnia. J Clin Pharmacol 1977; 17: 319-23. 7. Leibowitz M, Sunshine A. Long-term hypnotic efficacy and safety of triazolam and flurazepam. J Clin Pharmacol 1978; 18: 302-09. 8. Regestein QR. Pharmacology and hypnotic efficacy of triazolam: commentary 2. Pharmacotherapy 1983; 3: 146. 9. Greenblatt DJ, Shader RI, Divoll M, Harmatz JS. Adverse reactions to triazolam, flurazepam, and placebo in controlled clinical trials. J Clin Psychiatry 1984; 45: 192-95. 10. Morgan K, Oswald I. Anxiety caused by a short-life hypnotic. Br Med J 1982; 284: 942. 11. Bayer AJU, Bayer EM, Pathy MSJ, Stoker MJ. A double-blind controlled study of chlormethiazole and triazolam as hypnotics in the elderly. Acta Psychiatr Scand 1986; 73 (suppl 329): 104-11. 12. Adam K, Oswald I. Can a rapidly-eliminated hypnotic cause daytime anxiety? Pharmacopsychiatry 1989; 22: 115-19. 13. Adam K, Oswald I, Shapiro C. Effects of loprazolam and of triazolam on sleep and overnight urinary cortisol. Psychopharmacology 1984; 82: 389-94. 14. Bixler EO, Kales A, Brubaker BH, Kales JD. Adverse reactions to benzodiazepine hypnotics: spontaneous reporting systems. Pharmacology 1987; 35: 286-300.
GALACTOSE AND OVARIAN CANCER p 66) evidence that to ovarian cancer is hard to accept. is linked lactose causally dietary They stated that lactose consumption did not differ between patients with ovarian cancer and controls, and that there was no correlation between lactose consumption and red-cell transferase activity, which was lower in the cases compared with controls. But are they merely demonstrating a genetic component in ovarian cancer? Of all the sources of lactose Cramer et al listed, only yoghurt intake was significantly higher in the patients with ovarian cancer and, though they do not say so, yoghurt may well have provided a very small proportion of the total lactose intake. These workers cite two reports of animals on high galactose diets in which ovarian dysfunction was seen. It is worth recalling that in man when galactose is absorbed along with glucose, as after the digestion of lactose, the serum galactose concentrations are considerably lower than when the same amount of galactose is consumed without
SIR,-Dr Cramer and colleagues’ (July 8,
glucose.1 Physiology Department, United Medical and Dental Schools of Guy’s and St Thomas’s Hospitals, London SE1 9RT
IAN MACDONALD
1. Williams CA, Phillips T, Macdonald I. The influence of glucose levels in man. Metabolism 1983; 32: 250-56.
on serum
galactose
NUTRITIONAL LESSONS FROM WAR-TIME SIERRA LEONE
SIR,-Dr Tang and colleagues’ account (July 22, p 206) of an outbreak of beri-beri in The Gambia calls to mind an outbreak in Sierra Leone towards the end of the 1939-45 war. I was working in a hospital for African soldiers near Freetown, as a pathologist-presumably the nearest the Army came to finding a niche for a nutritionist. The naval presence in Freetown had their own medical services. A naval doctor had expressed concern about oedema in West African sailors: 3 or 4 a month were ill enough to be admitted to hospital, besides 30 or 40 ambulant cases. We agreed that beri-beri should be considered. The patients with oedema rapidly improved on a supplement, such as yeast, that contained B vitamins. Further inquiries revealed the cause of the beri-beri. Rice, the staple food of the Sierra Leone African, was not easy to come by during the war. The Army had drawn up a "West African diet scale", in which rice appeared only in four of the fourteen main meals a week: the rest were five meals with cocoa yams, three with millet, and two with cassava, the staples of one or other population in British West Africa. The scale was used for African Army personnel throughout British West Africa, from The Gambia to Nigeria, despite the widely differing habitual diets. The Navy was, as in many other respects, rather spoilt, and they managed to fmd rice for their own Sierra Leone personnel for most of their meals. Most of the rice, however, had to be imported and, unlike the local rice which was lightly polished if at all, it was highly polished white rice. I suggested that the Navy should mix some of this with the local rice, and they agreed, in the proportion of two parts of local rice to three parts of imported rice. The idea of supplying only unpolished local rice was ruled out because by then the sailors had a taste for polished rice and would (as we later found) have resisted being served unpolished rice only. The mixture was accepted, with bad grace, and after 2 or 3 months the monthly incidence of slight and severe beri-beri fell from about 40 to about 5 or 6. A few weeks later the incidence began to rise again. We found that the African non-commissioned officers had arranged with local millers to increase the milling until the rice was almost as white, and as popular, as the imported polished rice. As far as I know no case of beri-beri has been seen in African Army personnel in Sierra Leone. They had their own nutritional problems. Many African soldiers in Freetown had unpleasant dermatitis, mostly of the groin and scrotum. This had been present since the early part of the war, and was thought to be a sort of "Dhobie itch". Despite its inefficacy, methylene-blue and other material then used for the treatment of tinea were applied to treat this dermatitis. My calculation confirmed that the authorities in Whitehall had used their reference books and slide-rules well. All the essential nutrients were present, and in the correct quantities, in the West African diet scale. But it had been wrong of Whitehall to assume only one dietary pattern in the four countries of British West Africa. Our Sierra Leone soldiers were not at all happy with the form (garz) in which the cassava was provided, and they would not touch the millet (joro). A few soldiers, from Nigeria, did eatgari and joro, although not happily since they were not prepared in the same way as they were in Nigeria. Because of the refusal of the African hospital personnel to eatjoro, the catering officer reduced his order of millet from the Royal Army Service Corps (RASC). The resulting accumulation so embarrassed the RASC that an order appeared from on high making it an offence to "underdraw" millet from the stores. Lunching one day at the RASCs officers’ mess, I asked my host what the RASC did with the millet intended for consumption by Africans in their own unit. He looked over his shoulder and then said very quietly "Our soldiers use it for marking out the football
pitch". My calculation of the diet of the Sierra Leone soldier, as it was consumed-and not simply as it had been constructed in Whitehall-showed that it was significantly deficient in riboflavin, providing on average about 0-7 mg a day instead of the 1 ’3 mg the textbooks laid down as a minimum requirement. Today the recommended dietary allowance for an adult man is 1 ’7 mg, which was
about the amount calculated to be in the West African diet scale.
lormetazepam-takers. van der Kroefs observations about derealisation, panics, development of paranoid ideas, loss of weight and personality changes were also confirmed. 12 Upjohn-funded research has concentrated on dosing for 1-7 nights: little time for the development of tolerance. It is with regular intake of triazolam that brain function gradually changes and leads to daytime anxiety, while in the sleep laboratory the response of the brain after 3 weeks differs from the response to the first 2 doses.l3 To return to the 0 25 mg dosage: Bixler et al have reviewed the spontaneous adverse reports to the US Food and Drug Administration for triazolam, temazepam, and flurazepam and found a differential pattern. Daytime sedation was noted with all three, but triazolam caused agitation, hallucinations, and amnesia, not just with the 0-5 mg dose but frequently with the 0-25 mg dose too.14 van der Kroef was right, you were right to publish his letter in 1979, and the Netherlands have been right to ban triazolam since. People who complain of poor sleep are generally anxious people. If after 3 weeks they are even more anxious, doctor and patient alike easily attribute any change to the patient rather than to the drug. It is a matter for concern that halcion was marketed on the basis of deficient research. It should no longer be sold. University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh EH10 5HF
IAN OSWALD
1. van der Kroef C. Reactions to triazolam. Lancet 1979; ii: 526. 2. Barclay WR, Ayd FJ Jr, Callan JP, et al. Behavioural reactions to triazolam. Lancet
1979; ii: 1018. 3. MacLeod N, Kratochvil CH. Behavioural reactions to triazolam. Lancet 1979; ii: 638. 4. Lasagna L. The Halcion story: trial by media. Lancet 1980; i: 815. 5. Baker MI, Oleen MA. The use of benzodiazepine hypnotics in the elderly. Pharmacotherapy 1988; 8: 241-47. 6. Reeves RL. Comparison of triazolam, flurazepam, and placebo as hypnotics in geriatric patients with insomnia. J Clin Pharmacol 1977; 17: 319-23. 7. Leibowitz M, Sunshine A. Long-term hypnotic efficacy and safety of triazolam and flurazepam. J Clin Pharmacol 1978; 18: 302-09. 8. Regestein QR. Pharmacology and hypnotic efficacy of triazolam: commentary 2. Pharmacotherapy 1983; 3: 146. 9. Greenblatt DJ, Shader RI, Divoll M, Harmatz JS. Adverse reactions to triazolam, flurazepam, and placebo in controlled clinical trials. J Clin Psychiatry 1984; 45: 192-95. 10. Morgan K, Oswald I. Anxiety caused by a short-life hypnotic. Br Med J 1982; 284: 942. 11. Bayer AJU, Bayer EM, Pathy MSJ, Stoker MJ. A double-blind controlled study of chlormethiazole and triazolam as hypnotics in the elderly. Acta Psychiatr Scand 1986; 73 (suppl 329): 104-11. 12. Adam K, Oswald I. Can a rapidly-eliminated hypnotic cause daytime anxiety? Pharmacopsychiatry 1989; 22: 115-19. 13. Adam K, Oswald I, Shapiro C. Effects of loprazolam and of triazolam on sleep and overnight urinary cortisol. Psychopharmacology 1984; 82: 389-94. 14. Bixler EO, Kales A, Brubaker BH, Kales JD. Adverse reactions to benzodiazepine hypnotics: spontaneous reporting systems. Pharmacology 1987; 35: 286-300.
GALACTOSE AND OVARIAN CANCER p 66) evidence that to ovarian cancer is hard to accept. is linked lactose causally dietary They stated that lactose consumption did not differ between patients with ovarian cancer and controls, and that there was no correlation between lactose consumption and red-cell transferase activity, which was lower in the cases compared with controls. But are they merely demonstrating a genetic component in ovarian cancer? Of all the sources of lactose Cramer et al listed, only yoghurt intake was significantly higher in the patients with ovarian cancer and, though they do not say so, yoghurt may well have provided a very small proportion of the total lactose intake. These workers cite two reports of animals on high galactose diets in which ovarian dysfunction was seen. It is worth recalling that in man when galactose is absorbed along with glucose, as after the digestion of lactose, the serum galactose concentrations are considerably lower than when the same amount of galactose is consumed without
SIR,-Dr Cramer and colleagues’ (July 8,
glucose.1 Physiology Department, United Medical and Dental Schools of Guy’s and St Thomas’s Hospitals, London SE1 9RT
IAN MACDONALD
1. Williams CA, Phillips T, Macdonald I. The influence of glucose levels in man. Metabolism 1983; 32: 250-56.
on serum
galactose
NUTRITIONAL LESSONS FROM WAR-TIME SIERRA LEONE
SIR,-Dr Tang and colleagues’ account (July 22, p 206) of an outbreak of beri-beri in The Gambia calls to mind an outbreak in Sierra Leone towards the end of the 1939-45 war. I was working in a hospital for African soldiers near Freetown, as a pathologist-presumably the nearest the Army came to finding a niche for a nutritionist. The naval presence in Freetown had their own medical services. A naval doctor had expressed concern about oedema in West African sailors: 3 or 4 a month were ill enough to be admitted to hospital, besides 30 or 40 ambulant cases. We agreed that beri-beri should be considered. The patients with oedema rapidly improved on a supplement, such as yeast, that contained B vitamins. Further inquiries revealed the cause of the beri-beri. Rice, the staple food of the Sierra Leone African, was not easy to come by during the war. The Army had drawn up a "West African diet scale", in which rice appeared only in four of the fourteen main meals a week: the rest were five meals with cocoa yams, three with millet, and two with cassava, the staples of one or other population in British West Africa. The scale was used for African Army personnel throughout British West Africa, from The Gambia to Nigeria, despite the widely differing habitual diets. The Navy was, as in many other respects, rather spoilt, and they managed to fmd rice for their own Sierra Leone personnel for most of their meals. Most of the rice, however, had to be imported and, unlike the local rice which was lightly polished if at all, it was highly polished white rice. I suggested that the Navy should mix some of this with the local rice, and they agreed, in the proportion of two parts of local rice to three parts of imported rice. The idea of supplying only unpolished local rice was ruled out because by then the sailors had a taste for polished rice and would (as we later found) have resisted being served unpolished rice only. The mixture was accepted, with bad grace, and after 2 or 3 months the monthly incidence of slight and severe beri-beri fell from about 40 to about 5 or 6. A few weeks later the incidence began to rise again. We found that the African non-commissioned officers had arranged with local millers to increase the milling until the rice was almost as white, and as popular, as the imported polished rice. As far as I know no case of beri-beri has been seen in African Army personnel in Sierra Leone. They had their own nutritional problems. Many African soldiers in Freetown had unpleasant dermatitis, mostly of the groin and scrotum. This had been present since the early part of the war, and was thought to be a sort of "Dhobie itch". Despite its inefficacy, methylene-blue and other material then used for the treatment of tinea were applied to treat this dermatitis. My calculation confirmed that the authorities in Whitehall had used their reference books and slide-rules well. All the essential nutrients were present, and in the correct quantities, in the West African diet scale. But it had been wrong of Whitehall to assume only one dietary pattern in the four countries of British West Africa. Our Sierra Leone soldiers were not at all happy with the form (garz) in which the cassava was provided, and they would not touch the millet (joro). A few soldiers, from Nigeria, did eatgari and joro, although not happily since they were not prepared in the same way as they were in Nigeria. Because of the refusal of the African hospital personnel to eatjoro, the catering officer reduced his order of millet from the Royal Army Service Corps (RASC). The resulting accumulation so embarrassed the RASC that an order appeared from on high making it an offence to "underdraw" millet from the stores. Lunching one day at the RASCs officers’ mess, I asked my host what the RASC did with the millet intended for consumption by Africans in their own unit. He looked over his shoulder and then said very quietly "Our soldiers use it for marking out the football
pitch". My calculation of the diet of the Sierra Leone soldier, as it was consumed-and not simply as it had been constructed in Whitehall-showed that it was significantly deficient in riboflavin, providing on average about 0-7 mg a day instead of the 1 ’3 mg the textbooks laid down as a minimum requirement. Today the recommended dietary allowance for an adult man is 1 ’7 mg, which was
about the amount calculated to be in the West African diet scale.