1381 man better than any other current theory and is, at least, subject to experimental analysis. Your leader, in attempting to kill even modifications of the methylfolate-trap hypothesis, does not even hint at possible alternative explanations for
in
the considerable disturbances of folate metabolism which occur in vitamin-Bl2 deficiency. Department of Hæmatology,
Royal Free Hospital, London NW3 2QG.
A. V. HOFFBRAND.
IATROGENIC RUBELLA INFECTION SIR,-Obstetric registrars (whether male or female) and midwives are not ex officio immune from rubella and, if they acquire infection, become potent sources of danger for the 20% or so of women in the first trimester of preg1 nancy who are at risk from this virus. We have described and have recently encountered instances where a member of an obstetric unit developed rubella whilst working in close daily contact with pregnant women. The disturbing prospect of possible in-utero infection and consequent congenital abnormality resulting from such contact needs no
emphasis. We urge that no member of an obstetric unit should be at risk of contracting rubella and that all staff, before appointment, should be tested for antibodies to rubella virus and, if they are absent, the new member of the staff should be immunised. King’s College Hospital Medical School, Denmark Hill, London SE5 8RX.
2. 3.
thrombosis in women with no known The experience of these women subsequent to their first attack is also excluded. The adjusted observations are simultaneously standardised for age, parity, cigarette smoking, and social class, to the combined adjusted experience of takers, ex-takers, and controls, using the indirect method. The revised estimate of the risk of an association between oral contraceptive usage and venous thrombosis is similar The to the approximation published in our report. estimated attributable risks of 117 (98) per 100,000 pill users per year for superficial thrombosis and 81 (91) per 100,000 for deep thrombosis show little change. The numbers in parentheses indicate our former estimates. The increased rate in ex-takers could easily have occurred by chance. The new calculations have no bearing on the issue as to whether the reported observations were biased. Our conclusion that bias did not make an important contribution to the observed differences has been discussed elsewhere.2-4
attack of
venous
predisposing cause.
Royal College of General Practitioners, Oral Contraception Study, 8 Barlow Moor Road,
CLIFFORD R. KAY,
Manchester M20 0TR.
Recorder.
DYSKINESIAS DURING LEVODOPA THERAPY
R. N. P. SUTTON H. J. M. PULLEN.
ORAL CONTRACEPTIVES AND VENOUS THROMBOSIS SiR,-In the first reporta from the Royal College of General Practitioners’ Oral Contraception Study we emphasised that more data were desirable, and that many analyses called for more extensive consideration. Last November3indicated that we were recalculating data on pill usage and venous thrombosis. These calculations are now complete and a full report is being prepared. The accompanying table corresponds to table 7.3 in our report, and includes data from an additional 2l years, but, because of the more stringent exclusions the number of cases is smaller. All women having or developing a medical condition predisposing to venous thrombosis have been excluded. For pregnancy and the puerperium we have excluded the period of observation and associated events from the month after that in which the last menstrual period occurred to the calendar month after the end of the pregnancy, inclusive. Similarly, for any woman undergoing surgery we have excluded the whole calendar month 1.
operation was performed and the whole of the following month. The tabulated data represent the first when the
Sutton, R. N. P., Pullen, H. J. M., Pounds, F. J. Practitioner, 1973, 210, 551. Royal College of General Practitioners. Oral Contraceptives and Health. London, 1974. Kay, C. R. Lancet, 1974, ii, 1138.
SIR,-Professor Barbeau (March 29, p. 756) reported occasional dyskinesia, immediately preceding the " end-ofdose " akinesia, in parkinsonian patients treated with levodopa. The syndrome appeared at least three hours after a dose of drug. We have also observed this phenomenon.5.In addition we found 6 that a burst of dyskinesia, generally less severe, is often seen shortly after ingestion of a dose of levodopa, when the antiparkinsonian effect of the drug is beginning. The striking clinical combination of dyskinetic movements and symptoms of Parkinson’s disease during the " on " and/ " or off " effect may occur in a given patient only once, or repeatedly, during the day in relation to various levodopa doses," and at a time when plasma-dopa levels are rising (" on effect) or falling (" off " effect). In some patients the initial and terminal dyskinesias are separated by periods of good control of parkinsonian symptoms, with little or no associated dyskinesia. During these times dopa levels are at their peak. The dyskinesias at the time of the " on " and " off" effect vary in intensity and are not uncommon in our experience. Among 100 consecutive patients on long-term 4. Kay, C. R. ibid. p. 514. 5. Tolosa, E. S., Martin, W. E., Cohen, H. P.X int. Congr. Neurol., Excerpta med. int. Congr. Ser. 1973, 296, 241. 6. Tolosa, E. S., Martin, W. E., Cohen, H. P., Jacobson, R. L. Neuro-
logy, Minneap. 1975, 25,
177.
IDIOPATHIC VENOUS THROMBOSIS IN R.C.G.P. ORAL CONTRACEPTION STUDY: REVISED ESTIMATES OF RISK
*
P
in
the considerable disturbances of folate metabolism which occur in vitamin-Bl2 deficiency. Department of Hæmatology,
Royal Free Hospital, London NW3 2QG.
A. V. HOFFBRAND.
IATROGENIC RUBELLA INFECTION SIR,-Obstetric registrars (whether male or female) and midwives are not ex officio immune from rubella and, if they acquire infection, become potent sources of danger for the 20% or so of women in the first trimester of preg1 nancy who are at risk from this virus. We have described and have recently encountered instances where a member of an obstetric unit developed rubella whilst working in close daily contact with pregnant women. The disturbing prospect of possible in-utero infection and consequent congenital abnormality resulting from such contact needs no
emphasis. We urge that no member of an obstetric unit should be at risk of contracting rubella and that all staff, before appointment, should be tested for antibodies to rubella virus and, if they are absent, the new member of the staff should be immunised. King’s College Hospital Medical School, Denmark Hill, London SE5 8RX.
2. 3.
thrombosis in women with no known The experience of these women subsequent to their first attack is also excluded. The adjusted observations are simultaneously standardised for age, parity, cigarette smoking, and social class, to the combined adjusted experience of takers, ex-takers, and controls, using the indirect method. The revised estimate of the risk of an association between oral contraceptive usage and venous thrombosis is similar The to the approximation published in our report. estimated attributable risks of 117 (98) per 100,000 pill users per year for superficial thrombosis and 81 (91) per 100,000 for deep thrombosis show little change. The numbers in parentheses indicate our former estimates. The increased rate in ex-takers could easily have occurred by chance. The new calculations have no bearing on the issue as to whether the reported observations were biased. Our conclusion that bias did not make an important contribution to the observed differences has been discussed elsewhere.2-4
attack of
venous
predisposing cause.
Royal College of General Practitioners, Oral Contraception Study, 8 Barlow Moor Road,
CLIFFORD R. KAY,
Manchester M20 0TR.
Recorder.
DYSKINESIAS DURING LEVODOPA THERAPY
R. N. P. SUTTON H. J. M. PULLEN.
ORAL CONTRACEPTIVES AND VENOUS THROMBOSIS SiR,-In the first reporta from the Royal College of General Practitioners’ Oral Contraception Study we emphasised that more data were desirable, and that many analyses called for more extensive consideration. Last November3indicated that we were recalculating data on pill usage and venous thrombosis. These calculations are now complete and a full report is being prepared. The accompanying table corresponds to table 7.3 in our report, and includes data from an additional 2l years, but, because of the more stringent exclusions the number of cases is smaller. All women having or developing a medical condition predisposing to venous thrombosis have been excluded. For pregnancy and the puerperium we have excluded the period of observation and associated events from the month after that in which the last menstrual period occurred to the calendar month after the end of the pregnancy, inclusive. Similarly, for any woman undergoing surgery we have excluded the whole calendar month 1.
operation was performed and the whole of the following month. The tabulated data represent the first when the
Sutton, R. N. P., Pullen, H. J. M., Pounds, F. J. Practitioner, 1973, 210, 551. Royal College of General Practitioners. Oral Contraceptives and Health. London, 1974. Kay, C. R. Lancet, 1974, ii, 1138.
SIR,-Professor Barbeau (March 29, p. 756) reported occasional dyskinesia, immediately preceding the " end-ofdose " akinesia, in parkinsonian patients treated with levodopa. The syndrome appeared at least three hours after a dose of drug. We have also observed this phenomenon.5.In addition we found 6 that a burst of dyskinesia, generally less severe, is often seen shortly after ingestion of a dose of levodopa, when the antiparkinsonian effect of the drug is beginning. The striking clinical combination of dyskinetic movements and symptoms of Parkinson’s disease during the " on " and/ " or off " effect may occur in a given patient only once, or repeatedly, during the day in relation to various levodopa doses," and at a time when plasma-dopa levels are rising (" on effect) or falling (" off " effect). In some patients the initial and terminal dyskinesias are separated by periods of good control of parkinsonian symptoms, with little or no associated dyskinesia. During these times dopa levels are at their peak. The dyskinesias at the time of the " on " and " off" effect vary in intensity and are not uncommon in our experience. Among 100 consecutive patients on long-term 4. Kay, C. R. ibid. p. 514. 5. Tolosa, E. S., Martin, W. E., Cohen, H. P.X int. Congr. Neurol., Excerpta med. int. Congr. Ser. 1973, 296, 241. 6. Tolosa, E. S., Martin, W. E., Cohen, H. P., Jacobson, R. L. Neuro-
logy, Minneap. 1975, 25,
177.
IDIOPATHIC VENOUS THROMBOSIS IN R.C.G.P. ORAL CONTRACEPTION STUDY: REVISED ESTIMATES OF RISK
*
P
