61
heparin did not resolve the HUS. Multiple organ failure developed, and the patient died 30 days later. Necropsy revealed hyaline thrombosis of the glomerular arterioles. HUS, of unknown and probably diverse aetiology, is characterised by microangiopathic haemolytic anaemia, renal insufficiency, and thrombocytopenia. The syndrome can occur after infection, malignant disease, pregnancy, autoimmune disease, and drug use. Cyclosporin has frequently been associated with HUS in organ transplant recipients.3-6 Patients with HUS after BMT vary in type of transplant, drug and radiation conditioning, cyclosporin therapy, and complicating infections.7 Our patient had chronic uncontrollable GVHD and pulmonary infections, and had been given several drugs, including antibiotics, any of which might have caused HUS. However, on the basis of the clinical course, we consider that the most likely responsible drug was FK506.
TAKUJI ICHIHASHI
Department of Medicine, Nagoya University School of Medicine, Higashi-ku, Nagoya 461, Japan
TOMOKI NAOE HITOSHI YOSHIDA HITOSHI KIYOI HISASHI FUKUTANI KAZUAKI KUBO TATSUYA YAMAUCHI HIDEHIKO SAITO RYUZO OHNO
1. McCauley J, Bronsther O, Fung J, Todo S, Starzl TE. Treatment of cyclosporininduced haemolytic uraemic syndrome with FK506. Lancet 1989; ii: 1516. 2. Brown Z, Neild GH. FK-506 and haemolytic uraemic syndrome. Lancet 1990; 335: 412. 3. Atkinson K, Biggs JC, Hayes J, et al. Cyclosporin A associated nephrotoxidty in the first 100 days after allogeneic bone marrow transplantation: three distinct syndromes. Br J Haematol 1983; 54: 59-67. 4. Van Buren D, Van Buren CT, Flechner SM, Maddox AM, Verani R, Kahan BD. De novo hemolytic uremic syndrome in renal transplant recipients immunosupressed with cyclosporine. Surgery 1985; 98: 54-62. 5. Faure JL, Causse X, Bergeret A, Meyer F, Neidecker J, Paliard P. Cyclosporine induced hemolytic anemia in a liver transplant patient. Transplant Proc 1989; 21: 2242-43. 6. Goldman MH, Barnhart G, Mohanankumar T, et al. Cyclosporine in cardiac transplantation. Surg Clin N Am 1985; 65: 637-59. 7. Juckett M, Perry EH, Daniels BS, Weisdorf DJ. Hemolytic uremic syndrome following bone marrow transplantation. Bone Marrow Transplant 1991; 7: 405-09.
inhibited bacterial growth were found to be less than 5% in all isolates. We are now doing a double-blind controlled study. 5% acetic acid soaks are, of course, simple and inexpensive for eliminating
pseudomonas. I thank Dr J. Sloss, department of microbiology, Queen Elizabeth Military Hospital, Woolwich, UK, for help with this study.
Department of Surgery, Cambridge Military Hospital, Aldershot,
STEPHEN M. MILNER
Hants GU11 2AN, UK
1. Taylor K. Treatment of Bacillus pyocyaneus infection. JAMA 1916; 67: 1598-99. Phillips I, Lobo AZ, Fernandes R, Gundara NS. Acetic acid in the treatment of superficial wounds infected by Pseudomonas aeruginosa. Lancet 1968; i: 11-13. 3. Pruitt BA, Lindberg RB, McManus WF, Mason AD. Current approach to prevention and treatment of Pseudomonas aeruginosa infections in burned patients. Rev Infect Dis 1983; 5 (suppl): 889-94. 4. Lawrence JC. The bacteriology of burns. J Hosp Infect 1985; 6 (suppl B): 3-17. 5. Waymack JP, Pruitt BA. Burn wound care. Adv Surg 1990; 23: 261-90. 2.
Migraine SIR,-I
was
interested in Professor Lance’s paper
on
the
treatment of
migraine (May 16, p 1207) but wonder whether he can support his statement that sumatriptan has not been shown to affect the coronary circulation, when the British National Formulary of March, 1992, states quite explicitly that the drug should not be given by intravenous injection because it may cause coronary vasospasm and angina? Is Lance able to assure us that chest pain, angina, or electrocardiographic changes consistent with myocardial ischaemia have
not
been described in
patients who have received
sumatriptan? Department of Clinical Pharmacology, St Bartholomew’s Hospital Medical College, University of London, London EC1A 7BE, UK
*** This letter has been shown follows.-ED. L.
to
PAUL TURNER
Professor Lance, whose
reply
cannot give Professor Turner the he seeks. At the time of writing my article, sensations of pressure and tightness in the chest had been experienced by 3% of patients treated with sumatriptan 100-300 mg orally and by 5% of those after the subcutaneous administration of 4-8 mg with no electrocardiographic (ECG) evidence of cardiac ischaemia.1 Since then Willett et aP have reported a patient who developed chest pain, accompanied by ST elevation in the ECG, after sumatriptan 6 mg subcutaneously. Pain subsided and the ECG returned to normal in 22 min without subsequent increase in cardiac muscle enzymes. I would therefore regard the administration of sumatriptan as contraindicated in patients with suspected ischaemic heart disease.
SIR,-Unfortunately, I
Acetic acid to treat Pseudomonas aeruginosa in superficial wounds and burns SIR,-The use of acetic acid in the treatment of wound infection dates back to 1916 when Taylor found that application of a 1 % solution to war wounds led to elimination of "Bacillus pyocyaneus" after 2 weeks.l More recently Phillips et a12 demonstrated the efficacy of acetic acid compared with chlorhexidine or Eusol. However, there have been few studies in the clinical setting. In bums units, Pseudomonas aeruginosa is a major pathogen, causing tissue necrosis and systemic sepsis in major injuries.3 In a study from the MRC Burns Research Group, Birmingham, the organism was isolated from 59% of extensive burns.’ Local agents, such as para-aminomethyl benzene, sulphonamide, silver nitrate, aserbine, silver sulphadiazine, and mafenide acetate, have been used with varying degrees of success but have associated problems.5 For example, mafenide was linked with metabolic acidosis and severe pain, silver sulphadiazine with transient leucopenia, and silver nitrate with electrolyte abnormalities and black staining. The use of antibiotics is often hampered by multiple resistance. We have prospectively evaluated 5 % acetic acid soaks in a series of bums and superficial wounds. All patients had wound breakdown and delayed healing and all had yielded Pseudomonas spp for 2-14 days before treatment. Of the 9 patients treated, 7 had ulcers, 3.5-8.0 cm in diameter, five being decubitus and two venous. The remaining 2 had bums of 2% and 8% total body surface area. No patient complained of discomfort after the soaks, which were applied daily. Two of the wounds lost their Pseudomonas spp within 2 days and a further four, within a week. Only one was still contaminated at 3 weeks. After treatment and eradication of the species, healing readily occurred. All pseudomonas isolates were examined in vitro. Optimum concentrations of acetic acid that
reassurance
Institute of Neurological Sciences, Prince of Wales Hospital, Randwick, NSW 2031, Australia
JAMES W. LANCE
EG, Endersby CA, Smith RN, Talbot JCC. The safety and tolerability of sumatriptan: an overview. Eur Neurol 1991; 31: 339-14. 2. Willett F, Curzen N, Adams J, Armitage M. Coronary vasospasm induced by subcutaneous sumatriptan. BMJ 1992; 304: 1415. 1. Brown
SIR,-In his excellent overview of the treatment of migraine Professor Lance briefly mentions menstrual migraine, referring to our study on oestradiol treatment in this condition.1 Our study was not done with dermal patches but with a percutaneous oestradiol gel, and it demonstrated, in double-blind conditions, the efficacy of this gel in the prevention of pure menstrual migraine. This efficacy was confirmed in another randomised trial by Dennerstein et al .2 We think that the mode of administration plays an important part in the benefit/risk ratio of oestradiol in migraine prevention. Unlike Magos et aP we do not recommend oestradiol implants, which not only prevent attacks of migraine but also suppress menstruation and may induce endometrial risk when used long term. Transdermal
62
patches have not yet been shown to be effective in menstrual migraine and they might induce concentrations of oestradiol too low to have a preventive effect. In our study, favourable results were obtained by stabilising oestradiol plasma concentrations of 60 pg/ml during the perimenstrual week. Until now, percutaneous oestradiol gel has been the only formulation to prevent menstrual migraine in double-blind conditions without inducing menstrual disturbances, and furthermore it allows easy individual adaptation of doses. Department of Endocrinology and Reproductive Medicine, Hôpital Necker,
B. DE LIGNIÈRES
75015 Paris, France Service of
Neurology, Hôpital Saint-Antoine,
M. G. BOUSSER
Paris
Lignières B, Vincens M, Mauvais-Jarvis P, Mas JL, Touboul PJ, Bousser MG. Prevention of menstrual migraine by percutaneous oestradiol. BMJ 1986; 293: 1540. 2. Dennerstein L, Morse C, Burrows G, Oats J, Brown J, Smith M. Menstrual migraine: a double blind trial of percutaneous estradiol. Gynecol Endocrinol 1988; 2: 113-20. 3. Magos A, Zilkha KJ, Studd JW. Treatment of menstrual migraine by oestradiol implants. J Neurol Neurosurg Psychiatry 1983; 46: 1044-46. 1. De
SIR,-Dr Blau (May 16, p 1202) and Professor Lance summarise the pathogenesis and treatment possibilities of migraine. We have an interest in patients with menstrual migraine. Although the precise role of ovarian steroids in this disorder is not clear, cyclical fluctuations in their concentrations seem to be causally related to migraine symptoms. Gonadal hormones modulate neuronal activities in the brain! including the serotoninergic system, which seems to play an important part in migraine. Platelets have been suggested as a peripheral model for the study of serotoninergic mechanisms. They are said to have an important role in the female genital tract during human reproduction 2 On the one hand, Murdoch3noted platelet aggregation and adhesion around periovulatory ovine follicles, and Li et al4 reported that platelets are activated by platelet activating factor (PAF) during ovulation in immature rats. Activated platelets can release, for example, serotonin or histamine, which exert locally a direct stimulatory effect on steroid production of granulosa cells. On the other hand, Alecozay et alb demonstrated that endometriotic cells can produce PAF. During menstruation PAF is liberated from the disintegrated endometric cells into the bloodstream and activates the platelets. Consequently, the released monoamines produce vasodilatation and interstitial oedema due to increased capillary permeability. These changes may result in higher cerebral blood pressure with concomitant migraine because the skull cannot expand. We have therefore tried low-dose aspirin as prophylaxis in three patients with menstrual migraine. 2 x 100 mg aspirin daily was started two days before the onset of menstruation and was continued during menstruation. All patients had regular menstrual cycles and two used intrauterine devices. One took aspirin prophylaxis for a year, and the other two for three cycles. However, all patients reported a very good effect of aspirin prophylaxis (absence of migraine attack and headache; maintenance of working ability). This treatment was not a scientific study but was an attempt to help these three patients with severe menstrual migraine. We wish to draw to the attention of experts our findings which need to be confirmed in larger studies. University Women’s Hospital of Tubingen, D-7400 Tubingen, Germany 1. Pfaff
JOZSEF BODIS HANS-RUDOLF TINNEBERG
DA, McEwen BS. Action of estrogens and progestins
on nerve
cells Science
1983; 219: 808-14.
Harper MJK. Platelet-activating factor: a paracrine factor in preimplantation stages of reproduction. Biol Reprod 1989, 40: 907-12. 3. Murdoch WJ. Accumulation of thromboxane B2 within periovulatory ovine follicles: relationship to adhesion of platelets to endothelium. Prostaglandins 1986, 32: 2.
597-604. 4. Li
XM, Sagawa N, Ihara Y, et al. The involvement of platelet activating factor in thrombocytopenia and follicular rupture during gonadotropin-induced superovulation in immature rats. Endocrinology 1991, 129: 3132-38. 5. Bódis J, Torok A, Tinneberg HR, Hanf V, Hamon M, Cledon P. Influence of serotonin on progesterone and estradiol secretion of cultured human granulosa cells. Fertil Steril 1992; 57: 1008-11.
6.
Alecozay AA, DeLeon FD, Alecozay SL, Prien SD, Dorsett MJ, McGunegle D. Platelet-activating factor (PAF) and prostaglandin (PGE.) production by human endometrionc cells grown in culture. (47th annual meeting of the Amencan Fertility Society, Program Supplement, 1992; 126.)
SIR,-Dr Blau, in his article on the pathogenesis of migraine, cites clinical data on sumatriptan which are, unfortunately, misleading. The study referred t01 was designed to evaluate a two-dose regimen of sumatriptan. Administration of a randomised, placebo-controlled second dose was mandated by the design of the study, unless the patient was completely pain free 1 h after the first injection. Its use was not based on clinical need. Thus Blau’s comment that "58% of 615 patients needed a second injection 1 h after the first" is misleading. Efficacy was judged by the proportion of patients obtaining relief of headache 1 and 2 h after injection. By 2 h after a single 6 mg injection of sumatriptan 86% of patients had obtained relief, compared with 37% on placebo (p < 0001). Thus no more than 14% of patients failed to respond to sumatriptan in this study, not 23% as Blau suggests. Migraine attacks last from 4 to 72 h, whereas the half-life of sumatriptan is 2 h. The re-emergence of headache in a minority of patients is therefore not surprising. Further studies (unpublished) have shown that when symptoms do re-emerge another dose of sumatriptan provides relief. Glaxo Group Research Ltd, Greenford UB6 0HE, UK
A. J. PILGRIM D. K. LLOYD
Sumatriptan Study Group. Treatment of migraine attacks with sumatriptan. N Engl J Med 1991; 325: 316-21.
1. The Subcutaneous
SiR,—In Dr Blau’s review of theories of the pathogenesis of migraine, figure 1 shows that in a complete classic migraine attack the prodrome of fluid retention is corrected by diuresis in the recovery phase. These features could result from physiological responses to excessive intake of sodium (rise in serum in osmolarity--> osmolarity-oliguria-fluid retention->fall diuresis). The finding in premenstrual migraine of a higher serum osmolarity in the prodromal than in the headache phase of the attack 1 suggests that this is possible. Blau does not include salt in the table of triggers and possible triggers for migrainous headache. However, Brainard2 noted
clinically that ingestion of salt could trigger migraine, and subsequently reported that in 25 migraine subjects headache developed in 14 of 15 given sodium chloride in gelatin capsules and in only 1 of 10 given placebo capsules.3 He recommended a low-sodium diet "as one of the keys to migraine prevention".3 I fully endorse this statement, but would add that it is also important to advise migraine subjects to maintain an adequate intake of plain water. This is because a rise in osmolarity might occur as a result of: taking high-sodium mineral waters or aerated drinks, a diuresis induced by caffeine-containing drinks, and excessive loss of water from the skin and respiratory tract during exercise or in travel in a dry environment. Blau refers to evidence that insufficient metabolic availability of glucose could provoke a migraine attack. In my experience, sugary drinks and starchy foods may help to abort or relieve an attack. Even in the absence of hypoglycaemia, glucose as such or derived from sucrose or starch might act beneficially in migraine by enhancing intestinal absorption of water. I cannot agree with Professor Lance that diet is unimportant in the management of migraine in adults since salt, water, and carbohydrates should be taken into account. 308 Cricklewood Lane, London NW2 2PX, UK
JEFFREY J. SEGALL
G, Bisbocci D, Ceresa F. Sex hormones, prolactin levels, osmolarity and electrolyte patterns in menstrual migraine: relationship with fluid retention. Headache 1979; 19: 25-30. 2. Brainard JB. Salt load as a trigger for migraine. Minn Med 1976; 59: 232-33. 3. Brainard JB. Angiotensin and aldosterone elevation in salt-induced migraine. 1. Nattero
Headache 1981; 21: 222-26. 4
Segall JJ. Patient counselling. Community Health 1978; 9:
173-77.
heparin did not resolve the HUS. Multiple organ failure developed, and the patient died 30 days later. Necropsy revealed hyaline thrombosis of the glomerular arterioles. HUS, of unknown and probably diverse aetiology, is characterised by microangiopathic haemolytic anaemia, renal insufficiency, and thrombocytopenia. The syndrome can occur after infection, malignant disease, pregnancy, autoimmune disease, and drug use. Cyclosporin has frequently been associated with HUS in organ transplant recipients.3-6 Patients with HUS after BMT vary in type of transplant, drug and radiation conditioning, cyclosporin therapy, and complicating infections.7 Our patient had chronic uncontrollable GVHD and pulmonary infections, and had been given several drugs, including antibiotics, any of which might have caused HUS. However, on the basis of the clinical course, we consider that the most likely responsible drug was FK506.
TAKUJI ICHIHASHI
Department of Medicine, Nagoya University School of Medicine, Higashi-ku, Nagoya 461, Japan
TOMOKI NAOE HITOSHI YOSHIDA HITOSHI KIYOI HISASHI FUKUTANI KAZUAKI KUBO TATSUYA YAMAUCHI HIDEHIKO SAITO RYUZO OHNO
1. McCauley J, Bronsther O, Fung J, Todo S, Starzl TE. Treatment of cyclosporininduced haemolytic uraemic syndrome with FK506. Lancet 1989; ii: 1516. 2. Brown Z, Neild GH. FK-506 and haemolytic uraemic syndrome. Lancet 1990; 335: 412. 3. Atkinson K, Biggs JC, Hayes J, et al. Cyclosporin A associated nephrotoxidty in the first 100 days after allogeneic bone marrow transplantation: three distinct syndromes. Br J Haematol 1983; 54: 59-67. 4. Van Buren D, Van Buren CT, Flechner SM, Maddox AM, Verani R, Kahan BD. De novo hemolytic uremic syndrome in renal transplant recipients immunosupressed with cyclosporine. Surgery 1985; 98: 54-62. 5. Faure JL, Causse X, Bergeret A, Meyer F, Neidecker J, Paliard P. Cyclosporine induced hemolytic anemia in a liver transplant patient. Transplant Proc 1989; 21: 2242-43. 6. Goldman MH, Barnhart G, Mohanankumar T, et al. Cyclosporine in cardiac transplantation. Surg Clin N Am 1985; 65: 637-59. 7. Juckett M, Perry EH, Daniels BS, Weisdorf DJ. Hemolytic uremic syndrome following bone marrow transplantation. Bone Marrow Transplant 1991; 7: 405-09.
inhibited bacterial growth were found to be less than 5% in all isolates. We are now doing a double-blind controlled study. 5% acetic acid soaks are, of course, simple and inexpensive for eliminating
pseudomonas. I thank Dr J. Sloss, department of microbiology, Queen Elizabeth Military Hospital, Woolwich, UK, for help with this study.
Department of Surgery, Cambridge Military Hospital, Aldershot,
STEPHEN M. MILNER
Hants GU11 2AN, UK
1. Taylor K. Treatment of Bacillus pyocyaneus infection. JAMA 1916; 67: 1598-99. Phillips I, Lobo AZ, Fernandes R, Gundara NS. Acetic acid in the treatment of superficial wounds infected by Pseudomonas aeruginosa. Lancet 1968; i: 11-13. 3. Pruitt BA, Lindberg RB, McManus WF, Mason AD. Current approach to prevention and treatment of Pseudomonas aeruginosa infections in burned patients. Rev Infect Dis 1983; 5 (suppl): 889-94. 4. Lawrence JC. The bacteriology of burns. J Hosp Infect 1985; 6 (suppl B): 3-17. 5. Waymack JP, Pruitt BA. Burn wound care. Adv Surg 1990; 23: 261-90. 2.
Migraine SIR,-I
was
interested in Professor Lance’s paper
on
the
treatment of
migraine (May 16, p 1207) but wonder whether he can support his statement that sumatriptan has not been shown to affect the coronary circulation, when the British National Formulary of March, 1992, states quite explicitly that the drug should not be given by intravenous injection because it may cause coronary vasospasm and angina? Is Lance able to assure us that chest pain, angina, or electrocardiographic changes consistent with myocardial ischaemia have
not
been described in
patients who have received
sumatriptan? Department of Clinical Pharmacology, St Bartholomew’s Hospital Medical College, University of London, London EC1A 7BE, UK
*** This letter has been shown follows.-ED. L.
to
PAUL TURNER
Professor Lance, whose
reply
cannot give Professor Turner the he seeks. At the time of writing my article, sensations of pressure and tightness in the chest had been experienced by 3% of patients treated with sumatriptan 100-300 mg orally and by 5% of those after the subcutaneous administration of 4-8 mg with no electrocardiographic (ECG) evidence of cardiac ischaemia.1 Since then Willett et aP have reported a patient who developed chest pain, accompanied by ST elevation in the ECG, after sumatriptan 6 mg subcutaneously. Pain subsided and the ECG returned to normal in 22 min without subsequent increase in cardiac muscle enzymes. I would therefore regard the administration of sumatriptan as contraindicated in patients with suspected ischaemic heart disease.
SIR,-Unfortunately, I
Acetic acid to treat Pseudomonas aeruginosa in superficial wounds and burns SIR,-The use of acetic acid in the treatment of wound infection dates back to 1916 when Taylor found that application of a 1 % solution to war wounds led to elimination of "Bacillus pyocyaneus" after 2 weeks.l More recently Phillips et a12 demonstrated the efficacy of acetic acid compared with chlorhexidine or Eusol. However, there have been few studies in the clinical setting. In bums units, Pseudomonas aeruginosa is a major pathogen, causing tissue necrosis and systemic sepsis in major injuries.3 In a study from the MRC Burns Research Group, Birmingham, the organism was isolated from 59% of extensive burns.’ Local agents, such as para-aminomethyl benzene, sulphonamide, silver nitrate, aserbine, silver sulphadiazine, and mafenide acetate, have been used with varying degrees of success but have associated problems.5 For example, mafenide was linked with metabolic acidosis and severe pain, silver sulphadiazine with transient leucopenia, and silver nitrate with electrolyte abnormalities and black staining. The use of antibiotics is often hampered by multiple resistance. We have prospectively evaluated 5 % acetic acid soaks in a series of bums and superficial wounds. All patients had wound breakdown and delayed healing and all had yielded Pseudomonas spp for 2-14 days before treatment. Of the 9 patients treated, 7 had ulcers, 3.5-8.0 cm in diameter, five being decubitus and two venous. The remaining 2 had bums of 2% and 8% total body surface area. No patient complained of discomfort after the soaks, which were applied daily. Two of the wounds lost their Pseudomonas spp within 2 days and a further four, within a week. Only one was still contaminated at 3 weeks. After treatment and eradication of the species, healing readily occurred. All pseudomonas isolates were examined in vitro. Optimum concentrations of acetic acid that
reassurance
Institute of Neurological Sciences, Prince of Wales Hospital, Randwick, NSW 2031, Australia
JAMES W. LANCE
EG, Endersby CA, Smith RN, Talbot JCC. The safety and tolerability of sumatriptan: an overview. Eur Neurol 1991; 31: 339-14. 2. Willett F, Curzen N, Adams J, Armitage M. Coronary vasospasm induced by subcutaneous sumatriptan. BMJ 1992; 304: 1415. 1. Brown
SIR,-In his excellent overview of the treatment of migraine Professor Lance briefly mentions menstrual migraine, referring to our study on oestradiol treatment in this condition.1 Our study was not done with dermal patches but with a percutaneous oestradiol gel, and it demonstrated, in double-blind conditions, the efficacy of this gel in the prevention of pure menstrual migraine. This efficacy was confirmed in another randomised trial by Dennerstein et al .2 We think that the mode of administration plays an important part in the benefit/risk ratio of oestradiol in migraine prevention. Unlike Magos et aP we do not recommend oestradiol implants, which not only prevent attacks of migraine but also suppress menstruation and may induce endometrial risk when used long term. Transdermal
62
patches have not yet been shown to be effective in menstrual migraine and they might induce concentrations of oestradiol too low to have a preventive effect. In our study, favourable results were obtained by stabilising oestradiol plasma concentrations of 60 pg/ml during the perimenstrual week. Until now, percutaneous oestradiol gel has been the only formulation to prevent menstrual migraine in double-blind conditions without inducing menstrual disturbances, and furthermore it allows easy individual adaptation of doses. Department of Endocrinology and Reproductive Medicine, Hôpital Necker,
B. DE LIGNIÈRES
75015 Paris, France Service of
Neurology, Hôpital Saint-Antoine,
M. G. BOUSSER
Paris
Lignières B, Vincens M, Mauvais-Jarvis P, Mas JL, Touboul PJ, Bousser MG. Prevention of menstrual migraine by percutaneous oestradiol. BMJ 1986; 293: 1540. 2. Dennerstein L, Morse C, Burrows G, Oats J, Brown J, Smith M. Menstrual migraine: a double blind trial of percutaneous estradiol. Gynecol Endocrinol 1988; 2: 113-20. 3. Magos A, Zilkha KJ, Studd JW. Treatment of menstrual migraine by oestradiol implants. J Neurol Neurosurg Psychiatry 1983; 46: 1044-46. 1. De
SIR,-Dr Blau (May 16, p 1202) and Professor Lance summarise the pathogenesis and treatment possibilities of migraine. We have an interest in patients with menstrual migraine. Although the precise role of ovarian steroids in this disorder is not clear, cyclical fluctuations in their concentrations seem to be causally related to migraine symptoms. Gonadal hormones modulate neuronal activities in the brain! including the serotoninergic system, which seems to play an important part in migraine. Platelets have been suggested as a peripheral model for the study of serotoninergic mechanisms. They are said to have an important role in the female genital tract during human reproduction 2 On the one hand, Murdoch3noted platelet aggregation and adhesion around periovulatory ovine follicles, and Li et al4 reported that platelets are activated by platelet activating factor (PAF) during ovulation in immature rats. Activated platelets can release, for example, serotonin or histamine, which exert locally a direct stimulatory effect on steroid production of granulosa cells. On the other hand, Alecozay et alb demonstrated that endometriotic cells can produce PAF. During menstruation PAF is liberated from the disintegrated endometric cells into the bloodstream and activates the platelets. Consequently, the released monoamines produce vasodilatation and interstitial oedema due to increased capillary permeability. These changes may result in higher cerebral blood pressure with concomitant migraine because the skull cannot expand. We have therefore tried low-dose aspirin as prophylaxis in three patients with menstrual migraine. 2 x 100 mg aspirin daily was started two days before the onset of menstruation and was continued during menstruation. All patients had regular menstrual cycles and two used intrauterine devices. One took aspirin prophylaxis for a year, and the other two for three cycles. However, all patients reported a very good effect of aspirin prophylaxis (absence of migraine attack and headache; maintenance of working ability). This treatment was not a scientific study but was an attempt to help these three patients with severe menstrual migraine. We wish to draw to the attention of experts our findings which need to be confirmed in larger studies. University Women’s Hospital of Tubingen, D-7400 Tubingen, Germany 1. Pfaff
JOZSEF BODIS HANS-RUDOLF TINNEBERG
DA, McEwen BS. Action of estrogens and progestins
on nerve
cells Science
1983; 219: 808-14.
Harper MJK. Platelet-activating factor: a paracrine factor in preimplantation stages of reproduction. Biol Reprod 1989, 40: 907-12. 3. Murdoch WJ. Accumulation of thromboxane B2 within periovulatory ovine follicles: relationship to adhesion of platelets to endothelium. Prostaglandins 1986, 32: 2.
597-604. 4. Li
XM, Sagawa N, Ihara Y, et al. The involvement of platelet activating factor in thrombocytopenia and follicular rupture during gonadotropin-induced superovulation in immature rats. Endocrinology 1991, 129: 3132-38. 5. Bódis J, Torok A, Tinneberg HR, Hanf V, Hamon M, Cledon P. Influence of serotonin on progesterone and estradiol secretion of cultured human granulosa cells. Fertil Steril 1992; 57: 1008-11.
6.
Alecozay AA, DeLeon FD, Alecozay SL, Prien SD, Dorsett MJ, McGunegle D. Platelet-activating factor (PAF) and prostaglandin (PGE.) production by human endometrionc cells grown in culture. (47th annual meeting of the Amencan Fertility Society, Program Supplement, 1992; 126.)
SIR,-Dr Blau, in his article on the pathogenesis of migraine, cites clinical data on sumatriptan which are, unfortunately, misleading. The study referred t01 was designed to evaluate a two-dose regimen of sumatriptan. Administration of a randomised, placebo-controlled second dose was mandated by the design of the study, unless the patient was completely pain free 1 h after the first injection. Its use was not based on clinical need. Thus Blau’s comment that "58% of 615 patients needed a second injection 1 h after the first" is misleading. Efficacy was judged by the proportion of patients obtaining relief of headache 1 and 2 h after injection. By 2 h after a single 6 mg injection of sumatriptan 86% of patients had obtained relief, compared with 37% on placebo (p < 0001). Thus no more than 14% of patients failed to respond to sumatriptan in this study, not 23% as Blau suggests. Migraine attacks last from 4 to 72 h, whereas the half-life of sumatriptan is 2 h. The re-emergence of headache in a minority of patients is therefore not surprising. Further studies (unpublished) have shown that when symptoms do re-emerge another dose of sumatriptan provides relief. Glaxo Group Research Ltd, Greenford UB6 0HE, UK
A. J. PILGRIM D. K. LLOYD
Sumatriptan Study Group. Treatment of migraine attacks with sumatriptan. N Engl J Med 1991; 325: 316-21.
1. The Subcutaneous
SiR,—In Dr Blau’s review of theories of the pathogenesis of migraine, figure 1 shows that in a complete classic migraine attack the prodrome of fluid retention is corrected by diuresis in the recovery phase. These features could result from physiological responses to excessive intake of sodium (rise in serum in osmolarity--> osmolarity-oliguria-fluid retention->fall diuresis). The finding in premenstrual migraine of a higher serum osmolarity in the prodromal than in the headache phase of the attack 1 suggests that this is possible. Blau does not include salt in the table of triggers and possible triggers for migrainous headache. However, Brainard2 noted
clinically that ingestion of salt could trigger migraine, and subsequently reported that in 25 migraine subjects headache developed in 14 of 15 given sodium chloride in gelatin capsules and in only 1 of 10 given placebo capsules.3 He recommended a low-sodium diet "as one of the keys to migraine prevention".3 I fully endorse this statement, but would add that it is also important to advise migraine subjects to maintain an adequate intake of plain water. This is because a rise in osmolarity might occur as a result of: taking high-sodium mineral waters or aerated drinks, a diuresis induced by caffeine-containing drinks, and excessive loss of water from the skin and respiratory tract during exercise or in travel in a dry environment. Blau refers to evidence that insufficient metabolic availability of glucose could provoke a migraine attack. In my experience, sugary drinks and starchy foods may help to abort or relieve an attack. Even in the absence of hypoglycaemia, glucose as such or derived from sucrose or starch might act beneficially in migraine by enhancing intestinal absorption of water. I cannot agree with Professor Lance that diet is unimportant in the management of migraine in adults since salt, water, and carbohydrates should be taken into account. 308 Cricklewood Lane, London NW2 2PX, UK
JEFFREY J. SEGALL
G, Bisbocci D, Ceresa F. Sex hormones, prolactin levels, osmolarity and electrolyte patterns in menstrual migraine: relationship with fluid retention. Headache 1979; 19: 25-30. 2. Brainard JB. Salt load as a trigger for migraine. Minn Med 1976; 59: 232-33. 3. Brainard JB. Angiotensin and aldosterone elevation in salt-induced migraine. 1. Nattero
Headache 1981; 21: 222-26. 4
Segall JJ. Patient counselling. Community Health 1978; 9:
173-77.
