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agents (table), but it does not destroy phenylalanine, since the areas of turbidity were the same with or without autoclaving. Our findings indicate (1) that dibromol is better than cutasept spray for disinfecting the skin before taking a sample for the Guthrie test and (2) that the sample should be taken before (instead of after) administration of a dose of antibiotic. Also, (3) the plates should be subjected to an additional incubation period and (4) the cards containing antimicrobial substances should be autoclaved. We thank Mrs M. Schmidt for technical
help. P. CLEMENS C. VOLTMER C. PLETTNER
Department of Paediatrics, University of Hamburg, Martinistr 52, D-2000 Hamburg 20, FRG
1 Guthrie R, Susi A A simple phenylalanine method for detecting phenylketonuria large populations of newborn infants Pediatrics 1963; 32: 338-43. 2
in
Bracco G, Pagliardini S Guthrie test recalls due to antibiotic inhibition. Lancet 1983;i:
1331-32 3. Fisch RO, Anthony BF, Bauer
4 5
6 7
8
H, Bruhl H, Bruhl HH The effect of antibiotics on the results of the Guthrie test given to phenylketonuric patients J Pediatr 1968, 73: 685-89 Sander J. Storung des Phenylketonurie-Tests durch antibakterielle Wirkstoffe Off Gesundh- Wesen 1981; 43: 246 Lutz B. Schwierigkeiten bei der Durchführung des mikrobiologischen Hemmtests nach Guthrie. In: Bickel H, Wachtel U, eds Neugeborenen-Screening auf hereditare Stoffwechselstörungen Stuttgart-New York Thieme, 1983: 5-10. Benet LZ, Massoud N, Gambertogho JG. Pharmacokinetic basis for drug treatment. New York Raven, 1984: 435-40. Roberts RJ. Drug therapy in infants Philadelphia Saunders, 1984 58-66. Simon C, Stille W. Antibiotika-Therapie in Klinik und Praxis. Stuttgart-New YorkSchattauer, 1982: 59-61 and 264-69
DOMICILIARY OXYGEN THERAPY
SEROTONINERGIC IMMUNOFLUORESCENT NERVE FIBRES APPEAR IN HUMAN TEMPLE SKIN AFTER LITHIUM TREATMENT
SIR,-Nearly forty years after lithium was introduced for the of psychiatric disorders our understanding of the biochemical mechanisms underlying its clinical efficacy is still poor, and there is much inconsistency in its pharmacological actions in both experimental and human studies. Little attention has been paid to the complications of long-term lithium therapy. During a study of cluster headache, we observed a positive correlation between treatment
patients on lithium carbonate treatment and the appearance of serotonin-like immunofluorescent nerve fibres in temple skin punch biopsy specimens. These nerve fibres were found in 1 of 4 patients who had started lithium less than 10 days earlier, in both patients who had been on treatment for longer than 10 days, and in only 1 of 10 controls. Thus serotonin-positive nerve fibres were observed in 3 of the 6 patients on lithium carbonate. The 1 control with serotonin-positive nerve fibres had, 3 months before biopsy, had a 1-month course of lithium therapy at a higher dose of lithium carbonate (1200 mg daily) than that for most of the other patients. A further 6 of the control patients had also taken lithium carbonate previously but had not taken this drug for at least 7 weeks at the time of biopsy. Lithium may have a trophic effect, influenced by both dose and length of therapy, on serotoninergic nerve fibres. These findings are consistent with the increased serotoninergic fluorescence in pineal glands2 and increased rates of serotonin biosynthesis in midbrain and striate synaptosomes3and in whole brain 4,5 of rats after lithium administration. A recent study has also demonstrated lithium-induced enhancement of central 6
SiR,—Your Aug 17 editorial on long-term domiciliary oxygen therapy (LTOT) describes the domiciliary oxygen scene in Britain as "chaotic".
The scene in Catalonia (Spain) is similar. The Catalan Health Institute has been conducting a pilot study to confirm if the indications for the prescription of LTOT are correct. An area with 1112 million inhabitants has been selected, where more than 500 patients are now on LTOT. So far we have studied 263 patients, We have followed the criteria of the ACCP-NHLBI National Conference on Oxygen Therapyl for absolute indications for LTOT. However, partial indications were accepted: the use of oxygen with aerosols containing betaadrenergic agents in severe acute-on-chronic asthma; for conditions causing respiratory disability such as lung fibrosis, kyphoscoliosis; and in terminal lung cancer (see table).
serotoninergic neurotransmission. The immunohistochemical demonstration of serotonin-like immunoreactive nerve fibres in the cerebral circulation of various mammals including manadds to the mounting evidence that serotonin serves a neurotransmitter function in some cerebral blood vessels. In view of the powerful vasomotor action of serotonin and the further evidence presented here relating to the action of lithium on neuronal serotonin, it appears probable that there is altered vasomotor function in patients under lithium therapy. Furthermore, lithium treatment-which is not recommended in patients with impaired renal and hepatic function, cardiac disease, conditions with sodium imbalance, and pregnancy-may also be contraindicated in patients prone to cerebrovascular disorders. Department of Anatomy and Embryology and Centre for
CONFIRMATION OF PRESCRIPTION OF DOMICILIARY OXYGEN IN
Neuroscience,
University College London
263 PATIENTS Princess Margaret Migraine Clinic,
Charing Cross Hospital, London W6
K. DHITAL T. STEINER R. JOSEPH F. CLIFFORD-ROSE
Carter
88 of the 263 patients (33 - 4%) had a P,,02 below 55 mm Hg and only 27 of these 88 patients (10 .3% of the whole group) received oxygen for more than 15 hours a day. Our provisional conclusions are similar to that of the editorial. Few patients are receiving oxygen correctly. Patients for LTOT should be carefully selected because this treatment is very expensive. Some question the value of this therapy.2For this reason, if the patient carries on smoking or cannot achieve the 15 hours a day prescription, LTOT may be contraindicated, despite a low Pa02. If indiscriminate prescribing of domiciliary oxygen persists LTOT will become an expensive placebo.
Respiratory Service, Hospital de Bellvitge,
J. ESCARRABILL
l’Hospitalet (Barcelona), Spain; and Institut Català de la Area de la Costa de Ponent
Salut,
R. ESTOPÀ M. HUGUET F. MANRESA
1. ACCP-NHLBI National Conference on Oxygen Therapy Chest 1984; 86: 234-47 2 Grant IWB Oxygen in the home Br Med J 1982; 284: 417.
Bequest Hospital, Middlesbrough, Cleveland
J. ADAMS
Department of Neurology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
O. APPENZELLER
Department of Anatomy and Embryology and Centre for Neuroscience,
University College London, London WC1E 6BT
G. BURNSTOCK
1. Cade JF. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949; 38: 349-52. 2. Parvathi Devi S, Hariharasubramanian N, Venkoba Rao A. Lithium and the pinealadrenocortical axis. In: Johnson FN, ed. Lithium in medical practice. Lancaster: MTP, 1978: 235-42. 3. Knapp S, Mandell AJ. Short and longterm lithium administration: effects on the brain’s serotonergic biosynthetic system. Science 1973; 180: 645-47. 4. Perez-Cruet J, Tagliamonte A, Tagliamonte P, Gessa GL. Stimulation of serotonin biosynthesis by lithium. J Pharmacol Exp Ther 1971; 178: 325-30. 5. Poitou P, Guerinot F, Bohuon C. Effects of lithium on central metabolism of 5-hydroxytryptamine. Psychopharmacologia (Berl) 1974; 38: 75-80. 6. Blier P, De Montigny C. Short-term lithium administration enhances serotonergic neurotransmission: electrophysiological evidence in the rat CNS. Eur J Pharmacol 1985; 113: 69-77. 7 Griffith SG, Burnstock G. Immunohistochemical demonstration of serotonin in nerves supplying human cerebral and mesenteric blood vessels: Some speculations about their involvement in vascular disorders. Lancet 1983; i: 561-62.