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
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
