789

However, zopiclone and zolpidem do possess

one

important

property which distinguishes them from the BDZ-namely, their effects on sleep patterns as revealed by electroencephalography (EEG). BDZ hypnotics radically alter sleep patterns, with a decrease in slow-wave and rapid-eye-movement sleep but increases in stages I and II; zolpidem, however, increases slow-wave sleep without any alteration in rapid-eye-movement sleep. In other words zolpidem prolongs sleep more naturally. The effect of zopiclone on slow-wave sleep is controversial.6-8 Whether or not the production of a more normal EEG pattern of sleep influences the likelihood of dependence and withdrawal remains to be demonstrated, but at least this would seem to be a step in the right direction. Stress Clinic,

Maudsley Hospital, London SE5 8AZ, UK

DAVID WHEATLEY

D. Zopiclone: a non-benzodiazepine hypnotic controlled comparison to temazepam in insomnia. Br J Psychiatry 1985; 146: 312-14. 2. Deary IJ, Tait R. Effects of sleep disruption on cognitive performance and mood in medical house officers. Br Med J 1987; 295: 1513-16. 3. Wheatley D. Zolpldem: a new imidazopyridine hypnotic. Psychopharmacol Bull 1989; 25: 124-27. 4. Langer SZ, Arbilla S, Scatton B, Niddam R, Dubois A. Receptors involved m the mechanisms of action of zolpidem. In: Sauranet JP, Langer SZ, Morseli PL, eds. Imidazopyridine in sleep disorders: a novel experimental and therapeutic approach. New York: Raven Press, 1988: 55-70. 5. Wheatley D, ed. The anxiolytic jungle: where next? Chichester: John Wiley (in press). 6. Jovanovic UJ, Dreyfus JF. Polygraphical sleep recordings in insomniac patients under zopiclone or nitrazepam. Int Pharmacopsychiatry 1982; 17 (suppl 2): 136-45. 7. Wright NA, Belyavin A, Borland RG, Nicholason AN. Modulation of delta activity by hypnotics in middle-aged subjects: studies with a benzodiazepine (flurazepam) and a cyclopyrrolone (zopiclone). Sleep 1986; 9: 348-52. 8. Mamelak M, Scima A, Price V. Effects of zopiclone on the sleep of chronic insomniacs. Int Pharmacopsychiatry 1982; 17 (suppl 2); Pharmacology 1983; 27 (suppl 2): 156-64.

1. Wheatley

Antibody avidity test for recent infection with hepatitis C virus SIR,-Low-avidity antibody is the predominant antibody produced in the first few months after infection with many viruses.1-3 We have looked for such antibodies to hepatitis C virus (HCV) in sequential sera from a patient with post-transfusion hepatitis after blood transfusion. The patient was given eight units of blood in August, 1988, and raised levels of alanine aminotransferase, consistent with post-transfusion non-A, non-B hepatitis, developed 46 days later. Sera taken from the patient and stored sera from all eight donors were tested in the Ortho Diagnostics System anti-HCV enzyme immunoassay.4 The samples collected on the dates shown in the table were tested according to the manufacturer’s instructions and also with a modification in which 8 mol/1 urea was added to the wash fluid for the first wash step in the assay. An additional wash with the manufacturer’s recommended wash solution to remove the urea was then done. The urea dissociates low-avidity antibody from antigen. This early antibody is detected in the unmodified assay but not detected in the presence of 8 mol/1 urea. As the immune response matures, more avid antibodies develop which are not dissociated from the antigen by treatment with urea. Low-avidity antibody was predominant in the sample collected 116 days after blood transfusion, although this result was just below ANTI-HCV ASSAYS BY ORTHO ELISA WITH AND WITHOUT UREA WASH

*6 months before and 13 months after donation. tAfter transfusion.

positive cut-off. A sample collected at 179 days also contained significant low-avidity anti-HCV although high-avidity antibody was also present. Potent high-avidity antibody predominated by day 415, and would have masked any low-avidity antibody present. These findings are consistent with a recent infection with

the

HCV. We did not have enough serum from the implicated donation it by the modified technique but samples collected from the donor 6 months earlier and 1 year later were tested in this way. The HCV antibody in these samples was predominantly of high avidity, which is consistent with infection months or years to test

previously. We suggest that the presence of low-avidity HCV antibody can be used as an indication of recent infection, in the absence of a specific IgM test, albeit over the limited time span of acute infection. Clinical Microbiology and Public Health Laboratory, Addenbrooke’s Hospital, Cambridge CB2 2QW, UK

T. G. WREGHITT

J. J. GRAY S. ALOYISUS M. CONTRERAS J. A. J. BARBARA

North London Blood Transfusion Centre, Edgware, Middlesex

Changes in the avidity and specificity of early IgM and IgG antibodies. Immunology 1968, 14: 39-52. Morgan-Capner P, Thomas HIJ. Serological distinction between primary rubella and

1. Webster RG. The immune response to influenza III.

2. 3. 4.

reinfection. Lancet 1988; i: 1397. Gray JJ, Wreghitt TG. Immunoglobulin G avidity in Epstein-Barr virus infections in organ transplant recipients. Serodiag Immunother Infect Dis 1989; 3: 389-93. Kuo G, Choo Q-L, Alter HJ, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 1989; 244: 362-64.

Migraine and visual evoked potentials SIR,-We agree with Dr Peatfield (Feb 24, p 480) that a migraine replace the clinical diagnosis of headache. However, it is

test cannot

difficult

from a young child. in clinical use have been descriptions, unsupported by readily available diagnostic markers.1,2 Markers and correct definitions are fundamental to the evaluation of research and treatment.2 We can report that there is no correlation between VER (visual evoked response) amplitude and the duration of headache history. However, whether cause or consequence of migraine can be interpreted from this data is questionable because of the paroxysmal nature of migraine and what we know so far about the pathophysiology of migraine. The subject of patient personality is very interesting. In our study most patients were invited to attend the clinic from general practice, so the consultation was doctor initiated. Preliminary results from a study comparing childen with tension headache or migraine and controls indicate no increase in fast-wave activity in children with tension headache over that in controls. The diagnosis of common or classical migraine using VER with stimuli of different wavelengths is possible (unpublished). In reply to Dr van Dijk and colleagues’ letter (Feb 24, p 480) we believe that the reason why our VER analysis technique is more specific in terms of migraine diagnosis is that we have greatly amplified the EEG, on both x and y axes, after transient flash and pattern stimulation. Such a recording clearly differentiates the beta rhythm from other background activity such as electromyographic artifact. Other workers may have failed to notice enhanced beta rhythm in migraineurs because of the difficulties of quantifying beta rhythm with conventional EEG techniques. The VEPs consisted of averaged responses to five consecutive stimuli, and no attempt was made to analyse responses from individual stimuli. This was repeated four times for each stimulus parameter, and amplitudes and frequencies were averaged to quantify fast-wave activity (FWA). All analysis was made by peak-to-peak measurements in the last 250 ms of the recording. Analyses were done "blind", with no prior knowledge of clinical to

obtain

a

reliable

history

Furthermore, the migraine definitions

790

findings. Furthermore the test has proved to be successful in identifying migraineurs before any formal clinical diagnosis has been made.

Although some wave cancellation does occur, the use of five consecutive averaged responses was found to be the best number to provide the greatest specificity and sensitivity for migraine diagnosis. As such we feel that this technique is best described as a VER, rather than an EEG, although van Dijk and colleagues’ phrase "the reactivity of the EEG to light stimuli" is very descriptive. We would accept that since the FWA is present in all 500 ms of the recording the activity is not evoked by the visual stimuli. However, it is certainly "provoked" by the stimuli, since activity is minimal when no stimulation is presented and is enhanced by pattern stimuli in those patients diagnosed as migraine with aura. This would suggest that the FWA does not originate in the visual cortex, but occurs more anteriorly. Since the thalamus and hypothalamus form part of the reticular activating system, which has an effect on alpha and beta activity in the EEGthen it would be attractive to hypothesise that this activity may be of thalamic and/or hypothalamic origin, and may lend support to the hypothalamic aetiology of migraine.4 None of the children studied was on medication. Repeat VER measurements between attacks have shown no significant differences in FWA amplitude. We are about to complete a study comparing the FWA in childen with tension headache, migraine, and controls; preliminary results indicate that there is no significant increase in FWA in those children with tension headache. Birmingham & Midland Eye Hospital, Birmingham B3 2NS, UK

1. Blau JN. Towards a definition of migraine headache. Lancet 2. Edmeades J. Migraine markers. Headache 1988; 28: 568-69.

M. J. MORTIMER P. A. GOOD

1984; i: 444-45.

Singer W. Control of thalamic transmission by corticofugal and ascending reticular pathways in the visual system. Physiol Rev 1977; 57: 386. 4. Regan D. Electrical responses evoked from the human brain. Sci Am 1979; 241: 134. 3.

Exchange transfusion for malaria SIR,-Your Feb 10 editorial (p 324) recommends exchange

patients with heavily parasitised single case1 you express doubt about the mechanism of the effect of whole blood exchange, which has been used successfully in several patients. A young man was admitted to hospital 6 days after onset of fever. 36 % of his red blood cells were parasitised and his haematocrit was only 0,33.2 He died 80 min after infusion of quinine followed by hydrocortisone and combined sulfadoxine and pyrimethamine (’Fansidar’). Haemolysed red cells containing malarial pigment filled the capillaries to such an extent that red cells took up 75% of transfusion

for

malaria

erythrocytes. Citing

a

the lumen of vessels in the brain with a diameter of 12 j.lIl1 or less (many being 7 um or smaller) suggesting clogging of capillaries by rigid red cells.’ A normal red cell (7 pm) has to deform to pass through capillaries, many of which are narrower than this. When red cells are made non-deformable (rigid), blood viscosity in 7 j.lIl1 tubes is, at a haematocrit of045, almost infinite; raising the haematocrit strongly increases viscosity in 9 pm tubes also.3 Plasmodium falciparum maturation abolishes red cell deformability4 which depends on factorsmany of which are altered in falciparum malaria.5 Decreased deformability was judged to cause capillary obstruction in primate plasmodium infections.6 Plasma exchange (six exchanges plus seven haemodialyses at a department of nephrology) in the case you cite counteracted defibrination, renal failure, and dehydration but this does not contradict the view that plasmodium-induced red cell rigidity is a major cause of capillary obstruction in falciparum malaria-unless modem research on blood rheology is misleading. Unless all the waste (parasites, deformed red cell ghosts, altered haemoglobin)5 released by drugs is immediately removed by the

spleen it will, for a while at least, be deposited elsewhere in the circulation. If our patient had a blood volume of 5500 ml he disposed, within a week and on the basis of haematocrits, of debris from 825 ml of packed red blood cells and might have disposed of an additional 635 ml had he survived.2 It is possible that the decrease in parasitised cells prompted by antimalarial drugs yields a matching rate of clogging of capillaries. This could be part of the explanation for the link between quinine and blackwater fever, and it would cast doubt on your quest for effective antimalarial drugs under conditions where blood exchange is impracticable. Should whole blood exchange be done before effective drug therapy? Do we need to know, in circumstances not permitting blood exchange, whether venesection combined with plasma substitution and oxygen therapy ought to precede such therapy?2 And could filters be manufactured that clear the blood of rigid red cells of size 7 um or so but not of cells that are deformable to around 3 jjm? Aurora Hospital, 00250 Helsinki, Finland

JOHAN AHLQVIST

1. Bambauer R, Jutzler GA. Falciparum malaria successfully treated with plasma exchange. Plasma Ther Transf Technol 1984; 5: 343-47. 2. Ahlqvist J. Decreased red cell deformability and vascular obstruction in falciparum malaria illustrated by a fatal case. Scand JHaematol 1985; 35: 531-35. 3. Chien S. Determinants of blood viscosity and red cell deformability. ScandJ Clin Lab Invest 1981; 41 (suppl 156): 7-12. 4. Cranston HA, Boylan CW, Carrol GL, et al. Plasmodium falciparum maturation abolishes physiologic red cell deformability. Science 1984; 223: 400-03. 5. Pasvol G. Interaction of malaria parasites with red blood cells. Br Med Bull 1982; 38: 133-40 6. Miller LH, Chien S, Usami S. Decreased deformability of Plasmodium coatneyiinfected red cells and its possible relation to falciparum malaria. Am J Trop Med Hyg 1972; 21: 133-37.

SiR,—With reference to your Feb 10 editorial on exchange transfusion in malaria, we would like to report our experience. During the last 12 months we have seen 33 cases of Plasmodium falciparum malaria, 6 of them severe1 (table). All were treated with intravenous quinine dihydrochloride plus doxycycline hyclate. Our exchange transfusion policy was to use this procedure when parasitaemia was above 10% in association with renal, cerebral, or haemostatic abnormalities.2-4 On these criteria patients 4 and 5 were admitted to intensive care, where continuous haemodynamic and metabolic monitoring was feasible, and given exchange transfusion. (Despite the severity of her condition patient 6 could not be treated in this way because blood was not promptly available.) Patients 1,2, and 3 were managed with drug therapy; patient 2 required haemodialysis for renal failure. Patients 4 and 5 survived, as did the patients with a parasitaemia below 10% who were treated with chemotherapy alone. Despite the lack of evidence that sequestered parasitised red blood cells are removed during exchange transfusion, the process does rapidly DETAILS OF 3 CASES OF SEVERE MALARIA ELIGIBLE FOR EXCHANGE TRANSFUSION

Laboratory values on admission *9 units RBC, 7 units plasma. t5 units RBC, 4 units

plasma

Migraine and visual evoked potentials.

789 However, zopiclone and zolpidem do possess one important property which distinguishes them from the BDZ-namely, their effects on sleep pattern...
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