Bromocriptine and drug information
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1118 outcome for insemination is clearly different and inferior". The outcome is different in the sense that the offspring is usually not genetically related to the husband or male partner, but how are we to understand "inferior"? The use of drugs and/or surgery on healthy women to treat abnormalities in their partners certainly seems inferior both to treating infertile men directly and to bypassing the male’s infertility with donor insemination. Donor insemination is "inferior" to IVF-ET only for men who want their genetic lineage assured, but is far better for the women who otherwise have to undergo medical treatment. IVF-ET and GIFT are useful for some patients, but overall they are very expensive, largely unsuccessful, and potentially risky procedures. Although the Oregon plan is not perfect, it is at least an attempt to choose carefully and to take responsibility for the rationing that should occur within budget constraints, rather than to accept the ad hoc rationing to which Americans (and especially low-income Americans) are accustomed. The Lancet should attempt to clarify rather than confuse such complex policy decisions, and should be especially clear about distinguishing the treatments being discussed. Laura Shanner Centre for Bioethics, Department of Philosophy, University of Toronto, Toronto, Ontario, Canada M5G 1L4 1 Batman G. In vitro fertilisation in Australia: discussion paper and consultancy report. Canberra: Commonwealth Department of Community Services and Health, April, 1988. Bromocriptine and drug information SIR—You note (Sept 11, p 675) that the US Food and Drug Administration (FDA) will move to ban the use of bromocriptine for post-partum breast engorgement, and that the FDA has recommended since 1989 that this indication be dropped. I had a patient who had a stillbirth at 34 weeks’ gestation and who was given Parlodel (bromocriptine mesylate) to prevent lactation. Over the next few days she developed persistent severe unilateral headache. She had not previously had migraine. During pregnancy, delivery, and post partum she was normotensive. Headache is listed in the UK Data Sheet Compendium as an occasional side-effect of bromocriptine, but there was no indication of danger to the patient. In the Physician’s Desk Reference, the US equivalent of the Data Sheet Compendium, there is well-documented evidence of strokes in women on bromocriptine for post-partum breast-milk suppression, preceded by a severe unilateral headache, without hypertension. In view of this evidence I stopped bromocriptine and her headaches ceased. What concerns me is the striking difference in the information given to UK doctors in the Data Sheet Compendium, which is supplied by drug companies, and the equivalent information provided by drug companies in the USA. Another example of this discrepancy is the information provided by Wyeth Laboratories for the precautions of Premarin (conjugated oestrogens) in women with intact uteri. In the UK compendium the warning suggests that there is an increased risk of endometrial hyperplasia and carcinoma associated with unopposed oestrogens administered long term. The US reference provides more information (which is emphasised), including the fact that trials have shown a 4-13-fold risk of endometrial cancer. The failure of companies to give adequate warning of the potential side-effects of their drugs may lead doctors to continue to use a drug or failing to change to a more appropriate drug (ie, the use of protective progestogens), and this may put their patients at unnecessary risk. Why does the pharmaceutical industry in the UK furnish us with less information than in the USA, and why does the medical hierachy here accept that situation? Tom Bell Medical Centre, Okehampton, Devon EX20 1AY, UK Decreased cerebrospinal-fluid superoxide dismutase in amyotrophic lateral sclerosis SiR-Rosen et all reported that familial amyotrophic lateral sclerosis (ALS) is linked to the gene coding for superoxide dismutase, SOD 1. ALS is characterised by a selective loss of motor neurons, although the cause of motor neuron death remains unknown. Oxygen free radicals have been implicated as a potential cytotoxic mechanism, and might play a part in neuronal death in several disorders, including Parkinson’s disease and ischaemic injury.2 Cytosolic superoxide dismutase (CuZn SOD) is one of the enzymes that protect against oxygen toxicity by catalysing the dismutation of superoxide anions (02-) to oxygen and hydrogen peroxide (H2O2). It is not known whether CuZn SOD is involved in sporadic ALS. Since cerebrospinal fluid (CSF) reflects the enzyme concentration in the central nervous system, we assayed CuZn SOD concentration in the CSF of patients with sporadic ALS compared with that in age and sex matched controls. Ten patients (aged 52-79, mean 695; seven males) with sporadic ALS and ten controls (54-83, 69-4; seven males) were investigated. Lumbar puncture was done as part of the routine clinical investigation for ALS and degenerating lumbar-disc disease, respectively. CSF was stored at -20°C. CuZn SOD was measured by gel chromatography. 3 CuZn SOD in CSF was significantly lower in the ALS patients (mean 203 [SD 126] ag/L) than in the controls (369 [143] g/L)(p<0’02,Mest). CSF cells and protein were normal in both groups as was intracranial pressure. There was no relation between CuZn SOD and duration or severity of ALS. CSF studies are influenced indirectly by brain metabolic activity, but are one of the best approximations that can be achieved in vivo. There is increasing interest in the role of free radicals in the pathogenesis of neurological disorders. Bracco et al4 reported that decreased CuZn SOD in CSF in ALS could be attributable to non-specific neuronal loss, and possibly to a specific decrease of antioxidant activity associated with the disease. We have found low CuZn SOD in sporadic ALS. The decreased CuZn SOD in CSF could be attributed to a loss of motor neurons and reduction of an anti-oxidant capacity. We propose that an accumulation of toxic superoxide radicals due to low SOD activity may cause death of motor neurons in ALS patients. It is of interest that the SOD 1 gene can selectively affect motor neurons.s Yasuo Iwasaki, Ken Ikeda, Masao Kinoshita Fourth Department of Internal Medicine, Toho University Ohashi Hospital, Meguro-ku, Tokyo 153, Japan 1 Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362: 59-62. 2 Olanow CW. An introduction to the free radical hypothesis in Parkinson’s disease. Ann Neurol 1992; 32: S2-9. 3 Marklund SL, Holme E, Hellner L. Superoxide dismutase in extracellular fluids. Clin Chim Acta 1982; 126: 41-51. 4 Bracco F, Scarpa M, Rigo A, Battistin L. Determination of superoxide dismutase activity of the polarographic method of catalytic currents in the cerebrospinal fluid of aging brain and neurologic degenerative diseases. Proc Exp Soc Biol Med 1991; 196: 36-41. 5 Yarom R, Sapoznikov D, Havivi Y, Avraham KB, Schickler M, Groner Y. Premature aging changes in neuromuscular junctions of transgenic mice with an extra human CuZn SOD gene: a model for tongue pathology in Down’s syndrome. J Neurol Sci 1988; 88: 41-53.
Transcript of Bromocriptine and drug information
1118
outcome for insemination is clearly different and inferior".The outcome is different in the sense that the offspring isusually not genetically related to the husband or male partner,but how are we to understand "inferior"? The use of drugsand/or surgery on healthy women to treat abnormalities in theirpartners certainly seems inferior both to treating infertile mendirectly and to bypassing the male’s infertility with donorinsemination. Donor insemination is "inferior" to IVF-ET
only for men who want their genetic lineage assured, but is farbetter for the women who otherwise have to undergo medicaltreatment.
IVF-ET and GIFT are useful for some patients, but overallthey are very expensive, largely unsuccessful, and potentiallyrisky procedures. Although the Oregon plan is not perfect, it isat least an attempt to choose carefully and to take responsibilityfor the rationing that should occur within budget constraints,rather than to accept the ad hoc rationing to which Americans(and especially low-income Americans) are accustomed. TheLancet should attempt to clarify rather than confuse suchcomplex policy decisions, and should be especially clear aboutdistinguishing the treatments being discussed.
Laura ShannerCentre for Bioethics, Department of Philosophy, University of Toronto, Toronto, Ontario,Canada M5G 1L4
1 Batman G. In vitro fertilisation in Australia: discussion paper and
consultancy report. Canberra: Commonwealth Department ofCommunity Services and Health, April, 1988.
Bromocriptine and drug information
SIR—You note (Sept 11, p 675) that the US Food and DrugAdministration (FDA) will move to ban the use of
bromocriptine for post-partum breast engorgement, and thatthe FDA has recommended since 1989 that this indication be
dropped.I had a patient who had a stillbirth at 34 weeks’ gestation and
who was given Parlodel (bromocriptine mesylate) to preventlactation. Over the next few days she developed persistentsevere unilateral headache. She had not previously hadmigraine. During pregnancy, delivery, and post partum shewas normotensive. Headache is listed in the UK Data Sheet
Compendium as an occasional side-effect of bromocriptine, butthere was no indication of danger to the patient. In the
Physician’s Desk Reference, the US equivalent of the Data SheetCompendium, there is well-documented evidence of strokes inwomen on bromocriptine for post-partum breast-milk
suppression, preceded by a severe unilateral headache, withouthypertension. In view of this evidence I stopped bromocriptineand her headaches ceased.What concerns me is the striking difference in the
information given to UK doctors in the Data Sheet
Compendium, which is supplied by drug companies, and theequivalent information provided by drug companies in theUSA. Another example of this discrepancy is the informationprovided by Wyeth Laboratories for the precautions ofPremarin (conjugated oestrogens) in women with intact uteri.In the UK compendium the warning suggests that there is anincreased risk of endometrial hyperplasia and carcinomaassociated with unopposed oestrogens administered long term.The US reference provides more information (which is
emphasised), including the fact that trials have shown a
4-13-fold risk of endometrial cancer.The failure of companies to give adequate warning of the
potential side-effects of their drugs may lead doctors to
continue to use a drug or failing to change to a more appropriatedrug (ie, the use of protective progestogens), and this may puttheir patients at unnecessary risk. Why does the
pharmaceutical industry in the UK furnish us with less
information than in the USA, and why does the medicalhierachy here accept that situation?
Tom BellMedical Centre, Okehampton, Devon EX20 1AY, UK
Decreased cerebrospinal-fluid superoxidedismutase in amyotrophic lateral sclerosis
SiR-Rosen et all reported that familial amyotrophic lateralsclerosis (ALS) is linked to the gene coding for superoxidedismutase, SOD 1. ALS is characterised by a selective loss ofmotor neurons, although the cause of motor neuron deathremains unknown. Oxygen free radicals have been implicatedas a potential cytotoxic mechanism, and might play a part inneuronal death in several disorders, including Parkinson’sdisease and ischaemic injury.2 Cytosolic superoxide dismutase(CuZn SOD) is one of the enzymes that protect against oxygentoxicity by catalysing the dismutation of superoxide anions(02-) to oxygen and hydrogen peroxide (H2O2). It is not knownwhether CuZn SOD is involved in sporadic ALS. Since
cerebrospinal fluid (CSF) reflects the enzyme concentration inthe central nervous system, we assayed CuZn SODconcentration in the CSF of patients with sporadic ALScompared with that in age and sex matched controls.Ten patients (aged 52-79, mean 695; seven males) with
sporadic ALS and ten controls (54-83, 69-4; seven males) wereinvestigated. Lumbar puncture was done as part of the routineclinical investigation for ALS and degenerating lumbar-discdisease, respectively. CSF was stored at -20°C. CuZn SODwas measured by gel chromatography. 3
CuZn SOD in CSF was significantly lower in the ALSpatients (mean 203 [SD 126] ag/L) than in the controls (369[143] g/L)(p<0’02,Mest). CSF cells and protein were normalin both groups as was intracranial pressure. There was norelation between CuZn SOD and duration or severity of ALS.CSF studies are influenced indirectly by brain metabolic
activity, but are one of the best approximations that can beachieved in vivo. There is increasing interest in the role of freeradicals in the pathogenesis of neurological disorders. Bracco etal4 reported that decreased CuZn SOD in CSF in ALS could beattributable to non-specific neuronal loss, and possibly to aspecific decrease of antioxidant activity associated with thedisease. We have found low CuZn SOD in sporadic ALS. Thedecreased CuZn SOD in CSF could be attributed to a loss of
motor neurons and reduction of an anti-oxidant capacity. Wepropose that an accumulation of toxic superoxide radicals dueto low SOD activity may cause death of motor neurons in ALSpatients. It is of interest that the SOD 1 gene can selectivelyaffect motor neurons.s
Yasuo Iwasaki, Ken Ikeda, Masao KinoshitaFourth Department of Internal Medicine, Toho University Ohashi Hospital, Meguro-ku,Tokyo 153, Japan
1 Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Znsuperoxide dismutase gene are associated with familial amyotrophiclateral sclerosis. Nature 1993; 362: 59-62.
2 Olanow CW. An introduction to the free radical hypothesis inParkinson’s disease. Ann Neurol 1992; 32: S2-9.
3 Marklund SL, Holme E, Hellner L. Superoxide dismutase inextracellular fluids. Clin Chim Acta 1982; 126: 41-51.
4 Bracco F, Scarpa M, Rigo A, Battistin L. Determination of superoxidedismutase activity of the polarographic method of catalytic currents inthe cerebrospinal fluid of aging brain and neurologic degenerativediseases. Proc Exp Soc Biol Med 1991; 196: 36-41.
5 Yarom R, Sapoznikov D, Havivi Y, Avraham KB, Schickler M,Groner Y. Premature aging changes in neuromuscular junctions oftransgenic mice with an extra human CuZn SOD gene: a model fortongue pathology in Down’s syndrome. J Neurol Sci 1988; 88: 41-53.
