133

the basis of the increased ratio of 5-H1AA to 5-HT in many cortical tissues and 5-HlAA concentration in lumbar CSF that positively correlated with dementia rating of histologically verified AD .6 It is well known that drugs showing 5-HT lA agonism reduce aggression and depression in animals, so the proposed strategy will need careful evaluation. Cortical pyramidal neurons are probably also subject to cholinergic modulation4 but no ideal-ie, long lasting and nontoxic-acetylcholine esterase inhibitor has been tested with reliable methods; eg, no unequivocal diagnostic test for AD exists, other than by neurohistopathology. In conclusion, although the wellknown and exaggerated original claim for tetrahydroaminoacridine has caused pessimism with respect to reversing the prototypical transmitter deficit, approaches that target the affected cortical neurons should be pursued since they complement those aimed at on

(3-amyloid protein. We thank Dr J. V. their help.

D. M. BOWEN P. T. FRANCIS M. N. PANGALOS P. H. STEPHENS A. W. PROCTER

1. Bowen DM, Francis PT, Procter AW, Young AB. Treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry (in press). 2. Bjork L, Cornfield LJ, Nelson DL, et al. Pharmacology of the novel 5hydroxytryptamine 1A receptor antagonist (S)-5-fluoro-8-hydroxy-2(dipropylamino)tetralin: inhibition of (R)-8-hydroxy-2-(dipropylamino)tetralininduced effects. J Pharmacol Exp Therapeut 1991; 258: 58-65. 3. Liau LM, Sleight AJ, Pitha J, Peroutka SJ. Characterization of a novel and potent 5-hydroxytryptamine1A receptor antagonist. Pharmacol Biochem Behav 1991; 38: 555-59. 4. McCormick DA, Williamson A. Convergence and divergence of neurotransmitter action in human cerebral cortex. Proc Natl Acad Sci USA 1989; 86: 8098-102. 5. Pangalos MN, Francis PT, Middlemiss DN, Pearson RCA, Bowen DM. Selective destruction of a sub-population of cortical neurones by suicide transport of volkensin, a lectin from Adenia volkensii. J Neurosci Meth (in press). 6 Palmer AM, Stratmann GC, Procter AW, Bowen DM. Possible neurotransmitter basis of behavioural changes in Alzheimer’s disease. Ann Neurol 1988; 23: 616-20. 7. Pangalos MN, Malizia AL, Francis PT, et al Effect of psychotropic drugs on excitatory amino acid concentration in ventricular CSF from patients undergoing psychosurgery for intractable depression. Br J Psychiatry (in press).

SIR,-Dr Roberts and colleagues are to be congratulated on their

imaginative study of amyloid precursor protein in the damaged brain. However, I doubt that their findings elucidate-at least, in the way they suggest-the mechanisms whereby cerebral trauma may be followed in the long term by Alzheimer’s disease. There is evidence!,2 that platelets produce amyloid precursor of the type investigated by Roberts and colleagues. This substance may have a role in platelet aggregation or in the coagulation cascade. Cerebral injury causes widespread breaching of the blood-brain barrier. I suggest that what Roberts et al describe is not "a normal response to neuronal stress" that "can become a disease process in susceptible individuals" but rather a simple manifestation of multifocal cerebral vascular damage. Department of Neuropathology, Charing Cross Hospital,

PAUL D. LEWIS

London W6 8RF, UK

GM, Galasko D, Shapiro IP, Saitoh T. Stimulated platelets release amyloid &bgr;-protein precursor. Biochem Biophys Res Commun 1990; 170: 288-95. 2. Bush AI, Martins RN, Rumble B, et al. The amyloid precursor protein of Alzheimer’s disease is released by human platelets. J Biol Chem 1990; 265: 15977-83. 1. Cole

Prevention of

ultraviolet-light-induced herpes labialis

SIR,-Dr Rooney and colleagues (Dec 7, p 1419) report the prevention of ultraviolet-light-induced herpes labialis by

Herpes

once

every 2-3

sunlight. The mode of action of coumarin in herpes simplex remains to be elucidated; Pillar showed that its beneficial effect on bums was macrophage dependent. Coumarin given orally in a double-blind trial significantly decreased the recurrence of malignant melanoma.3 The primary lesions of melanoma are also associated with nerve endings and are affected by sunlight. Coumarin enhances delayed hypersensitivity reactions whereas ultraviolet light suppresses them/ Perhaps Rooney and colleagues’ study design might clarify the action of coumarin. Colman K Byrnes Research Centre, Beaumont Hospital, Dublin 9, Ireland

R. D. THORNES

1. Chambers

Halliwell, Dr D. M. A. Mann, and Prof D. Neary for

Miriam Marks Department of Neurochemistry, Institute of Neurology, Queen Square, London WC1N 3BG, UK

sunscreen.

sun-blocking agents since it need be applied only days for the first few weeks of excessive exposure to

convenient than

labialis could be

regarded

as an

occupational

hazard of Irish missionaries. The traditional use of tonka-bean camphor for the treatment of sunburn and ulceration led Sister Majella McKeman of the Medical Missionaries of Mary to devise a cream containing coumarin (1,2-benzopyrone), which is the main constituent of tonka-bean extract. She used 1 % coumarin in Silcock’s base, and it has been known for many years in our hospitals as Sr Majella’s cold-sore cream.’ As prophylaxis against herpes labialis it is more

M, Thomes RD, Mckernan M. Necrosis of skin induced by coumarin. Br Med J 1989; 298: 755. 2. Pillar NB. The ineffectiveness of coumarin treatment on thermal oedema of macrophage free rats. Br JExp Pathol 1976; 57: 170-74. 3 Thomes D, Daly L, O’Loughlin S, et al. Prevention of early recurrence of high risk malignant melanoma by coumarin Eur J Surg Oncol 1989; 15: 431-35. 4. Knpke ML. Immunological unresponsiveness induced by ultraviolet radiation. Immunol Rev 1984; 80: 87-102.

BEAM regimen and G-CSF in HTLV-Iassociated T-cell lymphoma SiR,—Adult T-cell leukaemia lymphoma (ATLL) is a recognised presentation of HTLV-1 infection. Despite new insights into its pathogenesis there has been little or no improvement in the treatment or survival of these patients. Although some clinical subtypes fare better than others,! in a large study only 18-7% (119/635) of patients achieved complete remission after chemotherapy, and the median survival was only 10 months? Although intensive combination chemotherapy has been used, further dose intensification with autologous bone-marrow rescue is in two-thirds of patients because of the presence of infiltration at diagnosisLaporte et al3 have reported in 5 patients with non-Hodgkin lymphoma the successful use of the haematopoietic growth factor ecogramostim (GM-CSF) instead of autologous marrow rescue after BEAM myeloablative chemotherapy. Furthermore, infusions of granulocyte colony stimulating factor (G-CSF) in lethally irradiated dogs led to haematopoietic reconstitution in the absence of marrow rescue.’ This suggests that G-CSF alone may produce haematopoietic reconstitution in patients who have received intensive chemotherapy and in whom marrow infiltration precludes the possibility of autologous marrow rescue. We report the treatment of a patient with ATLL with the BEAM regimen,’ followed by G-CSF without marrow rescue. A 47-year-old woman from Sierra Leone presented in May, 1991, with widespread eczema, secondarily infected with Staphylococcus aureus and herpes simplex virus. Examination was otherwise normal. She was seropositive for HTLV 1 (Serodia and Abbott) but negative for HIV-1 antibody. Full blood count was normal and blood smear showed no evidence of ATLL cells. Bone marrow was normal. She responded well to treatment with acyclovir, broad-spectrum antibiotics, and prednisolone. She presented again in August, 1991, with severe neck pain. She had bilateral tonsillar enlargement with tender firm cervical lymphadenopathy. Full blood count was normal, but occasional ATLL cells were present. Marrow aspirate revealed a reactive marrow with a small lymphocytic infiltrate but the bone-marrow biopsy specimen showed no evidence of lymphoma. In lymphomatous ATLL the marrow is less frequently affected; however, the degree of involvement may be difficult to assess because the infiltration is usually diffuse. Computed tomography of chest and abdomen showed widespread mediastinal and para-aortic lymphadenopathy. Strongyloides stercoralis larvae were identified in the stools. Lymph-node and left tonsillar biopsy showed infiltration by high-grade T-cell immunoblastic lymphoma. Bone marrow was harvested and stored. She was treated with the BEAM regimen (carmustine 300 mg/m2 on day 1, etoposide 200 mg/m2 on days 2-5, cytarabine 200 mg/m2 twice daily on days 2-5, and melphalan 140 mg/m2 on day 6). 24 h after finishing BEAM, G-CSF (Chugai) was

precluded

marrow

Prevention of ultraviolet-light-induced herpes labialis.

133 the basis of the increased ratio of 5-H1AA to 5-HT in many cortical tissues and 5-HlAA concentration in lumbar CSF that positively correlated wit...
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