PREGNANCY-ASSOCIATED α-GLYCOPROTEIN, ORAL CONTRACEPTIVES, AND RHEUMATOID ARTHRITIS
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1391 MANAGEMENT OF CEREBRAL ARTERIOVENOUS MALFORMATION SIR,-Dr Tansek and colleagues’ paper (May 21, p 1132) is a perfect example of how statistics coupled with inadequate data can be used in the management of a single case. Most patients with cerebral angiomas present with haemorrhage; the group presenting with epilepsy are the minority in what is a rare disease. There is only one published series in which sufficient patients have been gathered and an analysis made of the epilepsy group-namely, the 1966 cooperative study in the United States.’ I Unfortunately, although the statistics in that study were excellent as far as haemorrhage were concerned, the epilepsy group had a totally inadequate follow-up and, since the natural history of this disease is very long, no real conclusions can be drawn. There is no statistical evidence that the rate of bleeding within the epilepsy group differs from that in patients presenting with haemorrhage. The popular theory that there are "fitters" and "bleeders" is a myth. The other series cited by Tansek et al are selected and many of them are purely surgical. In a recent review of 129 patients at the National Hospital for Nervous Diseases, followed-up for thirty years, the annual bleeding rate was slightly higher amongst the patients presenting with epilepsy than among those who presented with a haemorrhage, though the difference was not significant. Seizures may represent small haemorrhages, and in nearly all pathological specimens there is evidence of suspected haemorrhage or at least haemosiderosis. In our series the surgical mortality for elective cases was under 1 % and the morbidity no more than 4%. The annual bleeding rate has been 3-4% and mortality rate per 163 proven haemorrhages was 4% plus a further 4% marked morbidity. It is, therefore, clear that in the younger patients surgery must be offered if this is technically feasible, though in the older patients (say 55), the natural history of the disease is probably no worse than the outlook after surgery. Department of Neurological Surgery, National Hospital, London WC1N 3BG CHARLES DAVIS SIR,-The application of science to art is always an interesting exercise, but Dr Iansek and colleagues’ use of decision analysis in the management of arteriovenous malformations was an excellent example of the dangers of mixing maths with medicine. Modern neurosurgeons faced with these difficult decisions do use current statistics which are constantly updated in the journals. Iansek et al assume that prognostic subgroupings are unnecessary. Apart from Pellettieri’s paper, which they cite, others (most recently Graf et al2) have shown that subgroupings reveal a marked difference in the risk of rebleeding and of mortality. The results of decision analysis based on these figures clearly supports surgery rather than inaction. I would not wish decision analysis to be dismissed because a conclusion has been based on figures at substantial variance with those of other studies. Midland Centre for Neurosurgery and Neurology, Warley, West Midlands B67 7JX E. R. HITCHCOCK PREGNANCY-ASSOCIATED &agr;-GLYCOPROTEIN, ORAL CONTRACEPTIVES, AND RHEUMATOID ARTHRITIS SIR,-Vandenbroucke et a13 have confirmed, in a case-control study of patients with rheumatoid arthritis (RA) and patients with soft tissue rheumatism or osteoarthritis,3 the finding of Wingrave and Kay4 that the incidence of RA is reduced in users of oral 1. Perret GE, Nishioka H. Report on the co-operative study of intracranial aneurysms and subarachnoid haemorrhage: Arteriovenous malformations. J Neurosurg 1966; 25: 467-90. 2. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations as part of their natural history. J Neurosurg 1983; 58: 331-37. 3. Vandenbroucke JP, Boersma JW, Festen JJM, Valkenburg HA, Cats A, Huber- Bruning O, Rasker JJ. Oral contraceptives and rheumatoid arthritis: Further evidence for a preventive effect. Lancet 1982; ii: 839-42. 4. Wingrave SJ, Kay CR. Reduction in incidence of rheumatoid arthritis associated with oral contraceptives. Lancet 1978; i: 569-71. PAG LEVELS (jg/ml)* IN PATIENTS WITH RHEUMATOID ARTHRITIS AND ANKYLOSING SPONDYLITIS AND CONTROLS DURING PREGNANCY *By solid phase radioimmunoassay. contraceptives (OC). Dr Vandenbroucke (May 7, p 1046) suggested further that the protective effect of OC use could be associated with induction of pregnancy associated a2-glycoprotein (PAG). Serum levels of PAG increase during pregnancy and during oestrogen treatment, except in the 10% or so of women who are "low inducers". The remission of RA seen during pregnancy, when PAG is increased, suggests a protective effect of this protein. Supporting this notion are two prospective studies6,7 demonstrating an inverse relation between PAG and disease activity in pregnant RA patients. However, in a prospective study of eleven RA patients and twelve patients with ankylosing spondylitis (AS), followed up during and after pregnancy, we were not able to confirm these findings;8 we found no correlation between the regression of disease symptoms and serum PAG levels (table). Raised PAG is commonly found in OC users and was also demonstrated in six non-pregnant patients who used OC. No change in activity of RA and AS was found in these patients when using OC. Furthermore, two women studied by us had their onset of RA during pregnancy, but they were not low PAG inducers. If even the temporary rise of PAG induced by previous use of OC can prevent the manifestation ofRA, as shown by Vandenbroucke et al,3 pregnancy should also be able to prevent RA by the same mechanism. The frequent onset of RA both during and after pregnancy9 shows that this is not so. Though PAG shows immunosuppressive properties in vitro, 10 its in vivo effect on rheumatoid inflammation and symptoms of RA remains to be clarified. The notion that the preventive effect of OC on the development of RA is caused by PAG remains a speculation. Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway MONIKA ØSTENSEN GUNNAR HUSBY CAPTOPRIL AND RESISTANT ASCITES SIR,-Ascites secondary to liver disease has been attributed both to the direct effects of portal hypertension and hypoalbuminaemia and to hyperaldosteronism. Ascites resistant to conventional therapy is rare but is potentially dangerous. We describe a patient with liver disease and hypergammaglobulinaemia (due to IgA myeloma) in whom captopril produced a dramatic improvement. A 76-year-old woman was admitted in September, 1982, with abdominal distention and severe dyspnoea. She had palmar 5. Damber MG, von Schoultz B, Stigbrand T, Tärnvik A. Pregnancy-zone protein present during pregnancy and hormonal treatment in women previously believed not to produce this protein. Am J Obstet Gynecol 1976; 125: 565-69. 6. Persellin RH, Wiginton DAF, Rutstein JE, Cohen MJ, Homer R, Goehrs R, Steele AD, Philips VK, Kradel RP. Pregnancy alpha-glycoprotein (PAG) and rheumatoid arthritis (RA) activity: a prospective analysis during gestation. Arthr Rheum 1982; 25 (suppl): S6. 7. Unger A, Kay A, Griffin AJ, Panayi GS. Disease activity and pregnancy-associated alpha2-glycoprotein in rheumatoid arthritis during pregnancy. Br Med J 1983; 286: 750-52. 8. Østensen M, von Schoultz B, Husby G. Comparison between serum alpha2-pregnancy associated globulin and activity of rheumatoid arthritis and ankylosing spondylitis during pregnancy. Scand J Rheumatol (in press). 9 Oka M. Effect of pregnancy on the onset and course of rheumatoid arthritis. Ann Rheum Dis 1953; 2: 227-29. 10. Bjørksten B, Söderström T, Damber MG, von Schoultz B, Stigbrand T. Polymorphonuclear leucocyte function during pregnancy. Scand J Immunol 1978; 8: 257-62. 1. Schiff L, Schiff ER. Diseases of the liver Philadelphia: J. B. Lippincott, 1982: 923-1234.
Transcript of PREGNANCY-ASSOCIATED α-GLYCOPROTEIN, ORAL CONTRACEPTIVES, AND RHEUMATOID ARTHRITIS
1391
MANAGEMENT OF CEREBRAL ARTERIOVENOUSMALFORMATION
SIR,-Dr Tansek and colleagues’ paper (May 21, p 1132) is aperfect example of how statistics coupled with inadequate data canbe used in the management of a single case.Most patients with cerebral angiomas present with haemorrhage;
the group presenting with epilepsy are the minority in what is a raredisease. There is only one published series in which sufficientpatients have been gathered and an analysis made of the epilepsygroup-namely, the 1966 cooperative study in the United States.’ I
Unfortunately, although the statistics in that study were excellent asfar as haemorrhage were concerned, the epilepsy group had a totallyinadequate follow-up and, since the natural history of this disease isvery long, no real conclusions can be drawn. There is no statisticalevidence that the rate of bleeding within the epilepsy group differsfrom that in patients presenting with haemorrhage. The populartheory that there are "fitters" and "bleeders" is a myth. The otherseries cited by Tansek et al are selected and many of them are purelysurgical.In a recent review of 129 patients at the National Hospital for
Nervous Diseases, followed-up for thirty years, the annual bleedingrate was slightly higher amongst the patients presenting withepilepsy than among those who presented with a haemorrhage,though the difference was not significant. Seizures may representsmall haemorrhages, and in nearly all pathological specimens thereis evidence of suspected haemorrhage or at least haemosiderosis. Inour series the surgical mortality for elective cases was under 1 % andthe morbidity no more than 4%. The annual bleeding rate has been3-4% and mortality rate per 163 proven haemorrhages was 4% plusa further 4% marked morbidity. It is, therefore, clear that in theyounger patients surgery must be offered if this is technicallyfeasible, though in the older patients (say 55), the natural history ofthe disease is probably no worse than the outlook after surgery.Department of Neurological Surgery,National Hospital,London WC1N 3BG CHARLES DAVIS
SIR,-The application of science to art is always an interestingexercise, but Dr Iansek and colleagues’ use of decision analysis inthe management of arteriovenous malformations was an excellent
example of the dangers of mixing maths with medicine. Modernneurosurgeons faced with these difficult decisions do use currentstatistics which are constantly updated in the journals. Iansek et alassume that prognostic subgroupings are unnecessary. Apart fromPellettieri’s paper, which they cite, others (most recently Graf et al2)have shown that subgroupings reveal a marked difference in the riskof rebleeding and of mortality. The results of decision analysis basedon these figures clearly supports surgery rather than inaction. Iwould not wish decision analysis to be dismissed because a
conclusion has been based on figures at substantial variance withthose of other studies.
Midland Centre for Neurosurgery and Neurology,Warley, West Midlands B67 7JX E. R. HITCHCOCK
PREGNANCY-ASSOCIATED &agr;-GLYCOPROTEIN, ORALCONTRACEPTIVES, AND RHEUMATOID ARTHRITIS
SIR,-Vandenbroucke et a13 have confirmed, in a case-controlstudy of patients with rheumatoid arthritis (RA) and patients withsoft tissue rheumatism or osteoarthritis,3 the finding of Wingraveand Kay4 that the incidence of RA is reduced in users of oral
1. Perret GE, Nishioka H. Report on the co-operative study of intracranial aneurysms andsubarachnoid haemorrhage: Arteriovenous malformations. J Neurosurg 1966; 25:467-90.
2. Graf CJ, Perret GE, Torner JC. Bleeding from cerebral arteriovenous malformations aspart of their natural history. J Neurosurg 1983; 58: 331-37.
3. Vandenbroucke JP, Boersma JW, Festen JJM, Valkenburg HA, Cats A, Huber-Bruning O, Rasker JJ. Oral contraceptives and rheumatoid arthritis: Furtherevidence for a preventive effect. Lancet 1982; ii: 839-42.
4. Wingrave SJ, Kay CR. Reduction in incidence of rheumatoid arthritis associated withoral contraceptives. Lancet 1978; i: 569-71.
PAG LEVELS (jg/ml)* IN PATIENTS WITH RHEUMATOID ARTHRITISAND ANKYLOSING SPONDYLITIS AND CONTROLS DURING PREGNANCY
*By solid phase radioimmunoassay.
contraceptives (OC). Dr Vandenbroucke (May 7, p 1046) suggestedfurther that the protective effect of OC use could be associated withinduction of pregnancy associated a2-glycoprotein (PAG).Serum levels of PAG increase during pregnancy and during
oestrogen treatment, except in the 10% or so of women who are"low inducers". The remission of RA seen during pregnancy,when PAG is increased, suggests a protective effect of this protein.Supporting this notion are two prospective studies6,7demonstrating an inverse relation between PAG and disease activityin pregnant RA patients. However, in a prospective study of elevenRA patients and twelve patients with ankylosing spondylitis (AS),followed up during and after pregnancy, we were not able toconfirm these findings;8 we found no correlation between theregression of disease symptoms and serum PAG levels (table).Raised PAG is commonly found in OC users and was also
demonstrated in six non-pregnant patients who used OC. Nochange in activity of RA and AS was found in these patients whenusing OC. Furthermore, two women studied by us had their onset ofRA during pregnancy, but they were not low PAG inducers. If eventhe temporary rise of PAG induced by previous use of OC canprevent the manifestation ofRA, as shown by Vandenbroucke et al,3pregnancy should also be able to prevent RA by the samemechanism. The frequent onset of RA both during and afterpregnancy9 shows that this is not so.Though PAG shows immunosuppressive properties in vitro, 10 its
in vivo effect on rheumatoid inflammation and symptoms of RAremains to be clarified. The notion that the preventive effect of OCon the development of RA is caused by PAG remains a speculation.Department of Rheumatology,Institute of Clinical Medicine,University of Tromsø,Tromsø, Norway
MONIKA ØSTENSENGUNNAR HUSBY
CAPTOPRIL AND RESISTANT ASCITES
SIR,-Ascites secondary to liver disease has been attributed bothto the direct effects of portal hypertension and hypoalbuminaemiaand to hyperaldosteronism. Ascites resistant to conventional
therapy is rare but is potentially dangerous. We describe a patientwith liver disease and hypergammaglobulinaemia (due to IgAmyeloma) in whom captopril produced a dramatic improvement.A 76-year-old woman was admitted in September, 1982, with
abdominal distention and severe dyspnoea. She had palmar
5. Damber MG, von Schoultz B, Stigbrand T, Tärnvik A. Pregnancy-zone proteinpresent during pregnancy and hormonal treatment in women previously believednot to produce this protein. Am J Obstet Gynecol 1976; 125: 565-69.
6. Persellin RH, Wiginton DAF, Rutstein JE, Cohen MJ, Homer R, Goehrs R, SteeleAD, Philips VK, Kradel RP. Pregnancy alpha-glycoprotein (PAG) and rheumatoidarthritis (RA) activity: a prospective analysis during gestation. Arthr Rheum 1982;25 (suppl): S6.
7. Unger A, Kay A, Griffin AJ, Panayi GS. Disease activity and pregnancy-associatedalpha2-glycoprotein in rheumatoid arthritis during pregnancy. Br Med J 1983; 286:750-52.
8. Østensen M, von Schoultz B, Husby G. Comparison between serum alpha2-pregnancyassociated globulin and activity of rheumatoid arthritis and ankylosing spondylitisduring pregnancy. Scand J Rheumatol (in press).
9 Oka M. Effect of pregnancy on the onset and course of rheumatoid arthritis. Ann RheumDis 1953; 2: 227-29.
10. Bjørksten B, Söderström T, Damber MG, von Schoultz B, Stigbrand T.
Polymorphonuclear leucocyte function during pregnancy. Scand J Immunol 1978;8: 257-62.
1. Schiff L, Schiff ER. Diseases of the liver Philadelphia: J. B. Lippincott, 1982:923-1234.
