1521

Fluoxetine doses

Eosinophil counts and percentage of leucocytes in patient with schizophrenia before and during challenge and rechallenge with clozapine. noted. After

further increase in the

following eosinophils, clozapine was discontinued and laboratory values rapidly became normal. The patient did not have any symptoms during this period. Other drugs were continued. The patient did not have collagen disease, leukaemia, Hodgkin’s disease, allergic illnesses, or symptoms suggestive of hypereosinophilic syndromes, such as Loeffler’s syndrome or endocarditis. Parasitic infections, however, were not excluded. In February, 1990, a severe relapse of refractory schizophrenia necessitated reintroduction of clozapine. Four days before starting treatment with clozapine 200 mg daily, leucocytes and differential count were normal (figure), but after ten days leucocytes and eosinophils were again abnormal and remained raised during the subsequent eleven days of treatment. Clozapine was then discontinued and all abnormalities rapidly disappeared. Again there were no symptoms. At this time parasitic infections eosinophilia week

to

18-1

were x

a

10"/1 leucocytes, of which 34%

were

excluded. A causal relation between leucocytosis and eosinophilia and the use of clozapine is highly probable in this patient. There was a clear temporal relation between adverse effects and course (challenge, "dechallenge", rechallenge), and other causes were ruled out or regarded as unlikely in view of the course. Although blood eosinophilia has been noted in some studies,3.4 we are not aware of any published case reports. Moreover, these effects are not mentioned in most data sheets (although blood count monitoring is obligatory) even though eosinophilia occurs in 5-10% of those taking clozapine.3,4 Medical practitioners prescribing clozapine should be aware of this effect, especially since it may accompany other white blood cell disorders. were

Netherlands Centre for Monitoring of Adverse Reactions to Drugs, PO Box 5406, 2280 H K Rijswijk, Netherlands

B. H. CH. STRICKER

Algemeen Psychiatrisch Centrum, Santpoort, Netherlands

J. A. E. TIELENS

Idanpaan-Heikkila J, Alhava E, Olkinuora M, Palva IP Agranulocytosis during treatment with clozapine. Eur J Clin Pharmacol 1977, 11: 193-98 2. De la Chapelle A, Kan C, Nurminen M, Hemberg S. Clozapine-induced agranulocytosis a genetic and epidemiological study. Hum Genet 1977; 37: 184-94. 3. Battegay R, Cotar B, Fleischhauer J, Rauchfleisch U. Results and side effects of treatment with clozapine (Leponex). Compr Psychiatry 1977; 18: 423-28. 4. Derichs H, Gehrmann A, Funfgeld EW, Ulmar G. Untersuchungen zur Hamatound Hepatotoxizitat des neuroliptikums Clozapm 44. Konferenz der Gesellschaft fur Biologische Chemie Hoppe-Seyler’s Z Phys Chem 1982, 363: 1300-01. 1

SIR,-It would be unfortunate if the conclusions drawn by Dr Baldwin (Sept 28, p 828) were to dissuade clinicians from increasing the dose of fluoxetine in patients not responding at the recommended "standard" dose of 20 mg. Whilst his comments are entirely reasonable and probably valid for most patients with depression treated in general practice or outpatient clinics, patients with more severe depression encountered in specialist units may respond selectively at a higher dose. Whilst it is true that dose escalation from 20 to 60 mg in patients not responding at 20 mg did not produce significant further improvement overall,l some features of depression such as cognitive disturbance significantly improved with the higher dose. There is a built-in handicap when assessing changes in Hamilton rating scale for depression data in patients treated with fluoxetine. Appetite and weight changes contribute to the total score, patients with a diminished appetite and weight loss due to fluoxetine (more likely at higher doses) appearing more depressed in terms of the total. This makes interpretation of this study difficult. Had the comparison been between 20 and 40 mg in non-responders, the results might have been different. A fixed dose study2 showed some evidence of a curvilinear response to fluoxetine with 53% responding at 20 mg, 61 % at 40 mg, and 48 % at 60 mg, all significantly superior to placebo (27%). Several studies3,4 suggest the need, in some patients with more severe depression, for a dose of 40 mg to achieve remission and to prevent early relapse. Whilst such higher doses might be accompanied by an increase in the rate of serotonin-related side-effects and hence compromise compliance in an outpatient setting, they should remain part of a treatment plan for inpatient units. Lilly Research Unit, Department of Psychiatry, UMDS, St Thomas’ Hospital, London SE1 7EH, UK

TONY HALE

1 Domiseif BE, Dunlop SR, Potvm JH, Wemicke JF. Effect of dose escalation after low-dose fluoxetme therapy. Psychopharmacol Bull 1989; 25: 71-79. 2. Wernicke JF, Dunlop SR, Domseif BE, Zerbe RL. Fixed dose fluoxetine therapy for depression. Psychopharmacol Bull 1987, 23: 164-68. 3. Hale AS, Stokes PE. The utility of serotonin reuptake inhibitors in endogenous depression and severe depression. In: Freeman HL. The uses of fluoxetine in clinical practice. London. Royal Society of Medicine, 1991. 15-25. 4. Fara M, Cohen L, Reiter S, et al. High dose fluoxetine in the treatment of depressed patients non-responding to a standard dose of fluoxetine. Biol Psychiatry 1991; 29: 638s.

Human

sensitivity to weak magnetic fields

SIR,-Exposure to electromagnetic fields (EMF) may increase the risk for cancer.1-3 This implies the existence of a mechanism for detecting the EMF and transducing it into a biological signal. We have been testing the hypothesis that the EMF is a stressor which causes signals in the central nervous system that subserve detection and response.4 We have found evidence for these signals in rabbits’ and describe here our first study in man. After they had given their informed consent fourteen healthy volunteers were exposed to magnetic fields produced by Helmholtz coils.6 The field strengths were similar to those produced near household electrical appliances. The saggital plane was perpendicular to the coil axis; the head and upper chest were within a field region that was uniform to within 5% of its nominal value. The average background 60 Hz magnetic field was less than 0-mG. All measuring equipment was located remotely from the room that contained the coils and the volunteer. We measured P(f)--the power in the electroencephalogram (EEG) in IlV2 at frequency f in Hz averaged over 2 s as determined by Fourier transformation of the EEG voltage signal-with the field on and off. The magnetic field was presented for 2 s, with a mean period between stimuli of 8s (range 5-11 s, varied randomly). The volunteer did not know when the magnetic field was on, and there were no visual or auditory cues. The effect of the EMF was assessed by comparing the EEG recorded during application of the field with that recorded during the 2 s immediately preceding the application. About 60 trials were done, and the first 50 artifact-free ones were

1522

EEG FREQUENCIES AFFECTED BY EXPOSURE TO MAGNETIC FIELDS

but information may be added at non-spiking regions of a neuron via voltage-gated channels whose cumulative effect is encoded by a subsequent spike.8 If the EMF produced an afferent signal consisting of such a modification of spontaneous neural activity, that could explain our observation of altered brain electrical activity in the absence of conscious perception. Departments of Orthopedic Surgery, Medicine, and Psychiatry, Louisiana State University Medical Center, Shreveport, Louisiana 71130, USA

GLENN B. BELL ANDREW A. MARINO ANDREW L. CHESSON FREDERICK A. STRUVE

1. Wertheimer N, Leeper E. Electrical wiring configurations and childhood cancer. AmJ 2.

C, P, 0

are

central, parietal, and occipital electrodes. respectlvely-

used in the subsequent analysis. Sham exposure was used as a control. The EEG was recorded from the central, parietal, and occipital electrodes (10-20 system) filtered to pass 0 3-35 Hz, and the signal was then divided and simultaneously recorded on an electroencephalograph and sampled at 200 Hz. The coefficients at 1-18Hz in increments of 05 Hz were obtained from the Fourier transform and analysed by Wilcoxon signed-rank test’ The criterion for concluding that a volunteer had detected the magnetic field was that the field produced at least two bilateral successes (difference between corresponding exposed and control epochs significant at p < 005) in at least one pair of electrodes, provided those changes were in the same direction. The probability that an effect might be due to chance was p < 0-02 (binomial distribution). Half the volunteers responded to the EMF by significant changes in EEG (table); no significant effects were observed during sham stimulation. P(f) for the frequencies significantly affected in three volunteers is shown in the figure. In all cases, less power was observed during the stimulus epochs compared with the control

epochs. Since the field-on and field-off epochs lasted only 2 s the locus of field transduction was probably in the nervous system--either a neuron or a perineural cell. Classic somatosensory pathways involve spike potentials and conscious perception of the stimulus,

Epidemiol 1979; 109: 273-84. Wright WE, Peters J, Mack T. Leukaemia magnetic fields. Lancet 1982; ii: 160.

in workers

exposed

to

electrical and

3. Coleman M, Bell J, Skeet R. Leukaemia incidence in electrical workers. Lancet 1983; i: 982. 4. Becker RO, Marino AA. Electromagnetism and life. Albany, NY: State University of New York Press, 1982. 5. Bell G, Marino AA. Electrical states in the rabbit brain can be altered by light and electromagnetic fields. Brain Res (in press). 6. Bell GB, Marino AA. Exposure system for production of uniform magnetic fields.

J Bioelectricity 1989; 8: 147-58. 7. Pfurtscheller

G, Aranibar A. Event-related cortical desynchronization detected by

power measurements of scalp EEG. Electroencephalog Clin Neurophysiol 1977; 42: 817-26. 8. Bialek W, Reike F, deRuyter van Steveninck RR, Warland D. Reading a neural code. Science 1991; 252: 1854-57.

Neopterin and psoriasis SiR,-Dr de Rie and co-workers (Nov 9, p 1208) question our finding (Sept 21, p 759) that neopterin concentrations correlate with psoriasis area and severity index (PASI). We found such a correlation during follow-up but did not have the no-treatment data described by de Rie et al. However, only one of our patients had had increased serum and urine neopterin levels before treatment with cyclosporin, and there was no close association between pretreatment neopterin levels and PASI, which accord with de Rie’s data. During our follow-up, neopterin concentrations rarely exceeded the upper limit of normal but increases and decreases in PASI were paralleled by neopterin concentrations in all patients. We still think that endogenous interferon-y is sufficient to induce production of neopterin by monocytes in psoriatic lesions. However, the changes in serum and urine neopterin concentrations may be less striking than those seen in other clinical situations like virus infection,’ simply because the molecule may not sufficiently penetrate from the periphery into the bloodstream. Department of Dermatology, and Institute of Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria

NORBERT SEPP DIETMAR FUCHS HELMUT WACHTER

D, Hausen A, Reibnegger G, Wemer ER, Wachter H. Neopterin as a marker for activated cell-mediated immunity: application in HIV infection. Immunol

1. Fuchs

Today 1988; 9: 150-55.

phenotype of branched-chain acyl-CoA oxidation defect

New clinical

SIR,-Clinical manifestations of multiple acyl-CoA dehydrogenase deficiency due to electron transfer flavoprotein (ETF) or ETF ubiquinone:oxidoreductase deficiency can vary considerably from a neonatal form, with multiple malformations, severe acidosis, hypoglycaemia, and hyperammonaemia, to milder, later-onset phenotypes Urinary excretion of glutaric acid, ethylmalonic acid, C6-C1O dicarboxylic acids, and several acylglycines is often indicative of an affected patient.2 In some cases, Change in EEG power (P) from 3 volunteers significantly affected by the magnetic field.

at

frequencies

,

p = P B -Po’ where P the field and control electrodes

B and Po are the mean power values recorded during epochs, respectively. Data from C (.)or 0 (n)

riboflavine treatment may be effective. We report here three unrelated Italian children presenting with a novel clinical phenotype, characteristic neuroradiological features, abnormal organicaciduria and biochemical evidence for branched-chain acyl-CoA oxidation defect. The patients presented with neonatal hypotonia followed by severe progressive pyramidal dysfunction with spastic diplegia,

Human sensitivity to weak magnetic fields.

1521 Fluoxetine doses Eosinophil counts and percentage of leucocytes in patient with schizophrenia before and during challenge and rechallenge with...
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