1350
findings. The ethical implications do not negate the importance of our work. Aluminium does appear in the brains of patients with hepatic failure and metastatic carcinoma but these are not long-term conditions so this cannot be used as an argument against a role for aluminium in AD. Aluminium accumulation in renal failure is very different; such patients have an acute exposure with greatly increased body levels of silicon which may protect them from the effects of aluminium, though neuropathological changes similar to those of AD develop in some.12,13 Department of Nephrology and Biochemistry, London Hospital and London Hospital Medical College, London E1 1BB, UK; and Division of Biology, Pharmaceutical Sciences, University of Aston, Birmingham
PAUL ALTMANN GILLIAN FARRAR SIMON WELCH JOHN A. BLAIR
1. Morris CM, Court JA, Moshtaghie AA, et al. Transferrin and transferrin receptors in normal brain and in Alzheimer’s disease. Biochem Soc Trans 1987; 15: 891-92. 2. Hams DC, Aisen P. Physical biochemistry ofthe transferrins. In: Loehr TM, ed. Iron carriers and iron proteins. New York: VCH, 1989. 3. Dacie JV, Lewis SM, Hoffbrand AV. Investigation of megaloblastic and irondeficiency anaemias. In: Practical haematology. Edinburgh: Churchill Livingstone, 1984. 4. Legget BA. Prevalence of haemochromatosis amongst asymptomatic Australians. Br J Haematol 1990; 74: 525-30. 5. Goya N, Miyazaki S, Kodate S, Ushio B. A family of congenital atransferrinaemia. Blood 1972; 40: 239-45. 6. Kaplan J, Craven C, Alexander J, et al. Regulation of the distribution of tissue iron. Ann NY Acad Sci 1988; 526: 124-35. 7. Candy JM, Oakley AE, Klinowsky J, et al. Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet 1986; i: 354-57. 8. Martyn CN, Barker DJP, Osmond C, Hams EC, Edwardson JA, Lacey RF. Geographical relation between Alzheimer’s disease and aluminium in drinking water. Lancet 1989; i: 59-62. 9. Kellett JM, Taylor A, Oram JJ. Aluminosilicates and Alzheimer’s disease. Lancet 1986; i: 682. 10. Barlow PJ, Francois PE, Goldberg I, et al. Trace metal abnormalities in long-stay hyperactive mentally handicapped children and agitated senile dements. J R Soc Med 1986; 79: 581-83. 11. Cochran M, Neoh S, Stephens E. Aluminium interactions with 67Ga uptake by human plasma and transferrin. Clin Chim Acta 1983; 132: 199-203. 12. Brun A, Dictor M. Senile plaques and tangles in dialysis dementia. Acta Pathol Microbiol Scand 1981; 89: 193-98. 13. Scholtz CL, Swash M, Gray A, Kogeorgos J, Marsh F. Neurofibrillary neuronal degeneration in dialysis dementia: a feature of aluminium toxicity. Clin Neuropathol 1987; 6: 93-97.
Guillain-Barré syndrome and Campylobacter jejuni infection SIR,-A high rate of Campylobacter jejuni infection has been reported in patients with the Guillain-Barre syndrome (GBS).1-s Although several possibilities have been suggested, we still have no direct evidence that GBS might be caused by this organism. We report the possibility that C jejuni infection could cause GBS by stimulating the production of antibodies that react with human peripheral nerve-myelin. Myelin proteins were extracted by Norton and Poduslo’s method6 from human sciatic nerve tissues, which were obtained within 24 h of death in patients with non-demyelinating diseases. In crude tissue extracts several protein-bands were electrophoresed and in the purified myelin fraction two main protein-bands at 35 kD and 145 kD and a faint band at 21 5kD were detected. From their migrating position in the gel they were identified as the myelin specific proteins PO, P2, and PI, respectively. An antiserum for C jejuni strain OH4384, a clinical isolate from a patient with GBS, was made in mice by intraperitoneal injection of whole viable bacterial cells. On immunoblotting the antiserum reacted strongly with PO, faintly but significantly with P2, but not with PI protein. This patient’s serum was not available for testing. But we identified these myelin-reactive antibodies in serum from another GBS patient, from whom C jejuni was not isolated, by immunoblotting. These results suggest that there are some protein(s) in Cjejuni which have similar antigenic properties to myelin protein PO and P2. This observation helps to explain the possible pathogenic relation between GBS and C jejuni infection. Studies of experimental allergic neuritis (an animal model of GBS) showed
that immunisation with the P2 protein can induce allergic neutitis.’-9 In addition, Carlo et al10 reported that the antigens to which the sensitised lymphocytes respond are the PO and P2 proteins. The crossreactive antibodies to PO and P2 proteins induced by C jejuni infection possibly cause neural diseases such as GBS. The nature of a crossreactive protein(s) of C jejuni, whether specific on a specific serotype or not, its location on the cell, and the presence of this antibody in cerebrospinal fluid of GBS patients needs to be determined. Department of Bacteriology, Faculty of Medicine, Kyushu University, Maedashi 3-1-1, Fukuoka, Japan
SHUJI FUJIMOTO KAZUNOBU AMAKO
1. Ropper AH. Campylobacter diarrhea and Guillain-Barré syndrome. Arch Neurol 1988; 45: 655-56. 2. Speed BR, Kaldor J, Watosn J, et al. Gampylobacter jejum/Campylobacter coliassociated Guillain-Barré syndrome: immunoblot confirmation of the serological response. Med J Aust 1987; 147; 13-16. 3. Kaldor J, Speed BR. Guillain-Barré syndrome Campylobacter jejuni: a serological study. Br MedJ 1984; 288: 1867-70 4. Molnar GK, Mertsola J, Erkko M. Guillain-Barré syndrome associated with Campylobacter infection. Br MedJ 1982; 285: 652. 5. Rhodes KM, Tattersfield AE. Guillain-Barrié syndrome associated with Campylobacter infection. Br Med J 1982; 285: 173-74. 6. Norton WT, Poduslo SE. Myelination in rat brain: method of myelin isolation. J Neurochem 1973; 21: 749-57. 7. Suzuki M, Kitamura K, Uyemura K, et al. Neuritogenic activity of peripheral nerve myelin proteins in Lewis rats. Neurosci Lett 1980; 19: 353-58. 8. Weise MJ, Hsieh D, Hoffman PM, et al. Bovine peripheral nervous system myelin P2 protein: chemical and immunological characterization of the cyanogen bromide peptides. J Neurochem 1980; 35: 393-99. 9. Kadlubowski M, Hughes RAC. Identification of the neuritogen for experimental allergic neuritis. Nature 1979; 277: 140-41. 10. Carlo DJ, Karkhanis YD, Bailey PJ, et al. Experimantal allergic neuritis: evidence for the involvement of the P0 and P2 proteins. Brain Res 1975; 88: 580-84.
Induction of von Willebrand disease type I by valproic acid SIR,-Under valproic acid (VPA) therapy most patients remain symptom-free but some have shown severe hepatotoxicity.l Haematological reactions2 include haemorrhagic diatheses, thrombocytopenia, and decreases in fibrinogen. 3,4 In our outpatient clinic we have frequently observed haemorrhage in children treated with VPA. Among 83 children on VPA we often found haemorrhagic disorders combined with a decrease in factor VIII/von Willebrand factor (vWF)-complex. Because the laboratory findings resembled those of congenital von Willebrand disease (vWD) we continued our observations in 30 children selected at random. These children (aged 1-18 years; 16 male and 14 female) were studied from March, 1985, until January, 1987. The daily dose was 300-2500 mg (typically 20-30 mg/kg) and the children had been on the drug for 6 months to 14 years. These children had not previously had a defect in haemostasis and they had no family history of bleeding disorders. We compared data in these children with those in 43 children (30 male and 13 female, aged 7 months to 14 years) with congenital vWD, excluding
Fig 1-Distribution of bleeding time among children treated with VPA and children with congenital vWD.
1351
How far should indications for growth hormone expand? SIR,-Your March 31 editorial criticises our paper reporting growth response to growth hormone (GH) treatment in four children with short stature associated with sporadic microcephaly.1 You correctly note that we had not specified the degree of mental retardation of the children investigated, and complained that we did not
discuss
our
views
on
GH
treatment
for non-GH-deficient
mentally handicapped children.
Fig 2-Distribution of factor VIII :C levels in children treated with VPA, children with congenital vWD, and controls.
multimer type II and III, and with a control group of 40 children (18 male and 22 female, aged 6 months to 18 years). We measured bleeding time (’Simplate I’, normal 25-95 min), FVIII:C activity (normal 70-100%), von Willebrand factor (vWF:Ag quantitative electroimmunoassay, normal 70-150%), and ristocetin co-factor activity (vWF:Rcof, normal above 70%) on formalin-fixed platelets.5 Multimer distribution of vWF:Ag was assayed with sodium dodecyl sulphate/agarose electrophoresis. We found a history of haemorrhage in 19 children on VPA and in 23 children with congenital vWD. Bleeding was usually mild (skin haemorrhages, epistaxis, and bleeding from gums). The bleeding time in children treated with VPA was prolonged almost to the same extent as that seen in congenital vWD (fig 1), the median being 7 min 45 s and 9 min 30 s, respectively. 7 children on VPA had abnormal bleeding times. The concentration of factor VIII:C in children under treatment with VPA ranged from 31% to 108% (median 80%) and 10 children had reduced levels (fig 2). In children treated with VPA the vWF:Ag concentration ranged between 25% and 116% (median 54 % ). In children with congenital vWD, vWF:Ag varied from 25% to 132% (median 56%). In children under therapy with VPA, vWF:Rcof ranged from 23% to 140% (median 63%). In children with congenital vWD, we found vWF:Rcof activities between 44% and 100% (median 70%). Multimer composition patterns tended to be abnormal in congenital vWD (normal 14%, intermediate 14%, type 172%) and in children on VPA (normal 13%, intermediate 20%, type I 67%). In no case of bleeding did VPA andconvulsive therapy have to be interrupted, and no correlation was found between the amount of factor VIII/vWF-complex and blood levels of VPA or duration of therapy. A decrease in factor VIII/vWF complex must be kept in mind for children on VPA, and if surgery is required or if bleeding is severe we recommend substitution with FVIII concentrates. Desmopressin should be avoided because we have observed one instance of convulsions during this therapy. VPA may influence the synthesis, protein release, or degradation of vWF:Ag.
Department of Paediatric Haematology and Oncology,
W. KREUZ R. LINDE M. FUNK R. MEYER-SCHROD E. FÖLL U. NOWAK-GÖTTL
Childen’s Diseases Centre and Internal Medicine Centre, Klinikum der Johann Wolfgang Goethe-Universitat, 6000 Frankfurt am Main 70, West Germany
ZS. VIGH I. SCHARRER
G. JACOBI
1. Jacobi
G, Thorbeck R, Ritz A, Janssen W, Schmidts HL. Fatal hepatoxicity in child phenobarbitone and sodium valproate. Lancet 1980; i: 712-13. 2. Sutor A, Jesdinsky-Buscher Chr. Veränderungen der Hamostase bei EpilepsieBehandlung mit Dipropylessigsäure. Fortschr Med 1976; 94: 411-14. 3. Jeavons PM. Antiepileptic drugs. New York: Raven Press, 1982: 601-10. 4. Loiseau P. Sodium valproate, platelet dysfunction and bleeding. Epilepsia 1981, 22: on
141-46. 5. Zuzel
ZM, Nilsson IM, Aberg M. A method for measuring plasma ristocetin cofactor activity: normal distribution and stability during storage. Thromb Res 1978; 12: 745-54.
With respect to the first point, we commented only generally on the mental retardation of our children and we would emphasise that all the children had a mild mental retardation with an intelligence quotient ranging from 51 to 70. We believe your second point has important ethical implications. The criteria for giving GH to non-GH-deficient short children are still undefined, and opinions differ. Several indices are thought to be relevant, such as the severity of growth retardation, very slow growth velocity, or a poor adult height prediction.2,3A paediatric endocrinologist will certainly choose the growth indices and, in some cases, the laboratory criteria that he judges most reliable, and will also take into account all the possible side-effects of GH therapy in decisions about whether to treat or not. In his consideration of the benefits and risks of treatment he might decide that the benefits outweigh the risks and that a specific child should therefore be treated. But if this child is also mentally retarded should the physician disregard his usual criteria and deny treatment? In other words, would mental handicap justify a difference being made between such a child and a mentally "normal" child? And if we should do so for GH, which other treatments should the handicapped child be denied? GIAN LUIGI SPADONI STEFANO CIANFARANI SERGIO BERNARDINI FABRIZIO VACCARO CINZIA GALASSO BRUNETTO BOSCHERINI
Department of Paediatrics, University of Rome, Rome 00173, Italy
2nd
1.
Spadoni GL, Cianfarani S, Bernardini S, Vaccaro F, Galasso C, Boscherini B. Growth hormone treatment in children with sporadic primary microcephaly. Am JDis Child 1989; 143: 1282-83. 2. Van Vliet GV, Styne DM, Kaplan SL, Grumbach MM. Growth hormone treatment for short stature. N Engl J Med 1983; 309: 1016-22. 3. Hindmarsh PC, Smith PJ, Pringle PJ, Brook CGD. The relationship between the response to growth hormone therapy and pretreatment growth hormone secretory status.
Clin Endocrinol 1988; 28: 559-64.
Effect of famotidine
on
deficit symptoms of
schizophrenia SIR,-We report
a case
where the administration of famotidine,
prescribed for peptic ulcer disease, was associated with improvement in the deficit symptoms of schizophrenia. A 36-year-old man with a 15-year history of schizophrenia was admitted 1 year ago with an acute exacerbation. He was found to have formal thought disorder, paranoid ideation, social withdrawal, psychomotor retardation, and emotional blunting. In the 5 years before admission he lived alone in a dark room in his parents’ house, avoiding contact with others. He was not under the care of a psychiatrist, nor was he taking any medication. On the inpatient unit he was put on haloperidol and benztropine. His thought disorder and paranoid symptoms resolved in 3 weeks; however, severe extrapyramidal symptoms developed which were only marginally responsive to increased benztropine. Neuroleptic treatment had to be suspended and the patient was put on medication-free observation. His of deficit symptoms schizophrenia remained unchanged. A medical work-up during this time revealed symptomatic peptic ulcer disease. The patient was started on famotidine 40 mg daily 3 weeks after he stopped taking psychotropic medications. The deficit symptoms improved 10 days after initiation of famotidine. The patient became more sociable, verbal, and active, and within 2 months he could take part in a rehabilitation work programme. He was discharged on famotidine only with close follow-up.
findings. The ethical implications do not negate the importance of our work. Aluminium does appear in the brains of patients with hepatic failure and metastatic carcinoma but these are not long-term conditions so this cannot be used as an argument against a role for aluminium in AD. Aluminium accumulation in renal failure is very different; such patients have an acute exposure with greatly increased body levels of silicon which may protect them from the effects of aluminium, though neuropathological changes similar to those of AD develop in some.12,13 Department of Nephrology and Biochemistry, London Hospital and London Hospital Medical College, London E1 1BB, UK; and Division of Biology, Pharmaceutical Sciences, University of Aston, Birmingham
PAUL ALTMANN GILLIAN FARRAR SIMON WELCH JOHN A. BLAIR
1. Morris CM, Court JA, Moshtaghie AA, et al. Transferrin and transferrin receptors in normal brain and in Alzheimer’s disease. Biochem Soc Trans 1987; 15: 891-92. 2. Hams DC, Aisen P. Physical biochemistry ofthe transferrins. In: Loehr TM, ed. Iron carriers and iron proteins. New York: VCH, 1989. 3. Dacie JV, Lewis SM, Hoffbrand AV. Investigation of megaloblastic and irondeficiency anaemias. In: Practical haematology. Edinburgh: Churchill Livingstone, 1984. 4. Legget BA. Prevalence of haemochromatosis amongst asymptomatic Australians. Br J Haematol 1990; 74: 525-30. 5. Goya N, Miyazaki S, Kodate S, Ushio B. A family of congenital atransferrinaemia. Blood 1972; 40: 239-45. 6. Kaplan J, Craven C, Alexander J, et al. Regulation of the distribution of tissue iron. Ann NY Acad Sci 1988; 526: 124-35. 7. Candy JM, Oakley AE, Klinowsky J, et al. Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet 1986; i: 354-57. 8. Martyn CN, Barker DJP, Osmond C, Hams EC, Edwardson JA, Lacey RF. Geographical relation between Alzheimer’s disease and aluminium in drinking water. Lancet 1989; i: 59-62. 9. Kellett JM, Taylor A, Oram JJ. Aluminosilicates and Alzheimer’s disease. Lancet 1986; i: 682. 10. Barlow PJ, Francois PE, Goldberg I, et al. Trace metal abnormalities in long-stay hyperactive mentally handicapped children and agitated senile dements. J R Soc Med 1986; 79: 581-83. 11. Cochran M, Neoh S, Stephens E. Aluminium interactions with 67Ga uptake by human plasma and transferrin. Clin Chim Acta 1983; 132: 199-203. 12. Brun A, Dictor M. Senile plaques and tangles in dialysis dementia. Acta Pathol Microbiol Scand 1981; 89: 193-98. 13. Scholtz CL, Swash M, Gray A, Kogeorgos J, Marsh F. Neurofibrillary neuronal degeneration in dialysis dementia: a feature of aluminium toxicity. Clin Neuropathol 1987; 6: 93-97.
Guillain-Barré syndrome and Campylobacter jejuni infection SIR,-A high rate of Campylobacter jejuni infection has been reported in patients with the Guillain-Barre syndrome (GBS).1-s Although several possibilities have been suggested, we still have no direct evidence that GBS might be caused by this organism. We report the possibility that C jejuni infection could cause GBS by stimulating the production of antibodies that react with human peripheral nerve-myelin. Myelin proteins were extracted by Norton and Poduslo’s method6 from human sciatic nerve tissues, which were obtained within 24 h of death in patients with non-demyelinating diseases. In crude tissue extracts several protein-bands were electrophoresed and in the purified myelin fraction two main protein-bands at 35 kD and 145 kD and a faint band at 21 5kD were detected. From their migrating position in the gel they were identified as the myelin specific proteins PO, P2, and PI, respectively. An antiserum for C jejuni strain OH4384, a clinical isolate from a patient with GBS, was made in mice by intraperitoneal injection of whole viable bacterial cells. On immunoblotting the antiserum reacted strongly with PO, faintly but significantly with P2, but not with PI protein. This patient’s serum was not available for testing. But we identified these myelin-reactive antibodies in serum from another GBS patient, from whom C jejuni was not isolated, by immunoblotting. These results suggest that there are some protein(s) in Cjejuni which have similar antigenic properties to myelin protein PO and P2. This observation helps to explain the possible pathogenic relation between GBS and C jejuni infection. Studies of experimental allergic neuritis (an animal model of GBS) showed
that immunisation with the P2 protein can induce allergic neutitis.’-9 In addition, Carlo et al10 reported that the antigens to which the sensitised lymphocytes respond are the PO and P2 proteins. The crossreactive antibodies to PO and P2 proteins induced by C jejuni infection possibly cause neural diseases such as GBS. The nature of a crossreactive protein(s) of C jejuni, whether specific on a specific serotype or not, its location on the cell, and the presence of this antibody in cerebrospinal fluid of GBS patients needs to be determined. Department of Bacteriology, Faculty of Medicine, Kyushu University, Maedashi 3-1-1, Fukuoka, Japan
SHUJI FUJIMOTO KAZUNOBU AMAKO
1. Ropper AH. Campylobacter diarrhea and Guillain-Barré syndrome. Arch Neurol 1988; 45: 655-56. 2. Speed BR, Kaldor J, Watosn J, et al. Gampylobacter jejum/Campylobacter coliassociated Guillain-Barré syndrome: immunoblot confirmation of the serological response. Med J Aust 1987; 147; 13-16. 3. Kaldor J, Speed BR. Guillain-Barré syndrome Campylobacter jejuni: a serological study. Br MedJ 1984; 288: 1867-70 4. Molnar GK, Mertsola J, Erkko M. Guillain-Barré syndrome associated with Campylobacter infection. Br MedJ 1982; 285: 652. 5. Rhodes KM, Tattersfield AE. Guillain-Barrié syndrome associated with Campylobacter infection. Br Med J 1982; 285: 173-74. 6. Norton WT, Poduslo SE. Myelination in rat brain: method of myelin isolation. J Neurochem 1973; 21: 749-57. 7. Suzuki M, Kitamura K, Uyemura K, et al. Neuritogenic activity of peripheral nerve myelin proteins in Lewis rats. Neurosci Lett 1980; 19: 353-58. 8. Weise MJ, Hsieh D, Hoffman PM, et al. Bovine peripheral nervous system myelin P2 protein: chemical and immunological characterization of the cyanogen bromide peptides. J Neurochem 1980; 35: 393-99. 9. Kadlubowski M, Hughes RAC. Identification of the neuritogen for experimental allergic neuritis. Nature 1979; 277: 140-41. 10. Carlo DJ, Karkhanis YD, Bailey PJ, et al. Experimantal allergic neuritis: evidence for the involvement of the P0 and P2 proteins. Brain Res 1975; 88: 580-84.
Induction of von Willebrand disease type I by valproic acid SIR,-Under valproic acid (VPA) therapy most patients remain symptom-free but some have shown severe hepatotoxicity.l Haematological reactions2 include haemorrhagic diatheses, thrombocytopenia, and decreases in fibrinogen. 3,4 In our outpatient clinic we have frequently observed haemorrhage in children treated with VPA. Among 83 children on VPA we often found haemorrhagic disorders combined with a decrease in factor VIII/von Willebrand factor (vWF)-complex. Because the laboratory findings resembled those of congenital von Willebrand disease (vWD) we continued our observations in 30 children selected at random. These children (aged 1-18 years; 16 male and 14 female) were studied from March, 1985, until January, 1987. The daily dose was 300-2500 mg (typically 20-30 mg/kg) and the children had been on the drug for 6 months to 14 years. These children had not previously had a defect in haemostasis and they had no family history of bleeding disorders. We compared data in these children with those in 43 children (30 male and 13 female, aged 7 months to 14 years) with congenital vWD, excluding
Fig 1-Distribution of bleeding time among children treated with VPA and children with congenital vWD.
1351
How far should indications for growth hormone expand? SIR,-Your March 31 editorial criticises our paper reporting growth response to growth hormone (GH) treatment in four children with short stature associated with sporadic microcephaly.1 You correctly note that we had not specified the degree of mental retardation of the children investigated, and complained that we did not
discuss
our
views
on
GH
treatment
for non-GH-deficient
mentally handicapped children.
Fig 2-Distribution of factor VIII :C levels in children treated with VPA, children with congenital vWD, and controls.
multimer type II and III, and with a control group of 40 children (18 male and 22 female, aged 6 months to 18 years). We measured bleeding time (’Simplate I’, normal 25-95 min), FVIII:C activity (normal 70-100%), von Willebrand factor (vWF:Ag quantitative electroimmunoassay, normal 70-150%), and ristocetin co-factor activity (vWF:Rcof, normal above 70%) on formalin-fixed platelets.5 Multimer distribution of vWF:Ag was assayed with sodium dodecyl sulphate/agarose electrophoresis. We found a history of haemorrhage in 19 children on VPA and in 23 children with congenital vWD. Bleeding was usually mild (skin haemorrhages, epistaxis, and bleeding from gums). The bleeding time in children treated with VPA was prolonged almost to the same extent as that seen in congenital vWD (fig 1), the median being 7 min 45 s and 9 min 30 s, respectively. 7 children on VPA had abnormal bleeding times. The concentration of factor VIII:C in children under treatment with VPA ranged from 31% to 108% (median 80%) and 10 children had reduced levels (fig 2). In children treated with VPA the vWF:Ag concentration ranged between 25% and 116% (median 54 % ). In children with congenital vWD, vWF:Ag varied from 25% to 132% (median 56%). In children under therapy with VPA, vWF:Rcof ranged from 23% to 140% (median 63%). In children with congenital vWD, we found vWF:Rcof activities between 44% and 100% (median 70%). Multimer composition patterns tended to be abnormal in congenital vWD (normal 14%, intermediate 14%, type 172%) and in children on VPA (normal 13%, intermediate 20%, type I 67%). In no case of bleeding did VPA andconvulsive therapy have to be interrupted, and no correlation was found between the amount of factor VIII/vWF-complex and blood levels of VPA or duration of therapy. A decrease in factor VIII/vWF complex must be kept in mind for children on VPA, and if surgery is required or if bleeding is severe we recommend substitution with FVIII concentrates. Desmopressin should be avoided because we have observed one instance of convulsions during this therapy. VPA may influence the synthesis, protein release, or degradation of vWF:Ag.
Department of Paediatric Haematology and Oncology,
W. KREUZ R. LINDE M. FUNK R. MEYER-SCHROD E. FÖLL U. NOWAK-GÖTTL
Childen’s Diseases Centre and Internal Medicine Centre, Klinikum der Johann Wolfgang Goethe-Universitat, 6000 Frankfurt am Main 70, West Germany
ZS. VIGH I. SCHARRER
G. JACOBI
1. Jacobi
G, Thorbeck R, Ritz A, Janssen W, Schmidts HL. Fatal hepatoxicity in child phenobarbitone and sodium valproate. Lancet 1980; i: 712-13. 2. Sutor A, Jesdinsky-Buscher Chr. Veränderungen der Hamostase bei EpilepsieBehandlung mit Dipropylessigsäure. Fortschr Med 1976; 94: 411-14. 3. Jeavons PM. Antiepileptic drugs. New York: Raven Press, 1982: 601-10. 4. Loiseau P. Sodium valproate, platelet dysfunction and bleeding. Epilepsia 1981, 22: on
141-46. 5. Zuzel
ZM, Nilsson IM, Aberg M. A method for measuring plasma ristocetin cofactor activity: normal distribution and stability during storage. Thromb Res 1978; 12: 745-54.
With respect to the first point, we commented only generally on the mental retardation of our children and we would emphasise that all the children had a mild mental retardation with an intelligence quotient ranging from 51 to 70. We believe your second point has important ethical implications. The criteria for giving GH to non-GH-deficient short children are still undefined, and opinions differ. Several indices are thought to be relevant, such as the severity of growth retardation, very slow growth velocity, or a poor adult height prediction.2,3A paediatric endocrinologist will certainly choose the growth indices and, in some cases, the laboratory criteria that he judges most reliable, and will also take into account all the possible side-effects of GH therapy in decisions about whether to treat or not. In his consideration of the benefits and risks of treatment he might decide that the benefits outweigh the risks and that a specific child should therefore be treated. But if this child is also mentally retarded should the physician disregard his usual criteria and deny treatment? In other words, would mental handicap justify a difference being made between such a child and a mentally "normal" child? And if we should do so for GH, which other treatments should the handicapped child be denied? GIAN LUIGI SPADONI STEFANO CIANFARANI SERGIO BERNARDINI FABRIZIO VACCARO CINZIA GALASSO BRUNETTO BOSCHERINI
Department of Paediatrics, University of Rome, Rome 00173, Italy
2nd
1.
Spadoni GL, Cianfarani S, Bernardini S, Vaccaro F, Galasso C, Boscherini B. Growth hormone treatment in children with sporadic primary microcephaly. Am JDis Child 1989; 143: 1282-83. 2. Van Vliet GV, Styne DM, Kaplan SL, Grumbach MM. Growth hormone treatment for short stature. N Engl J Med 1983; 309: 1016-22. 3. Hindmarsh PC, Smith PJ, Pringle PJ, Brook CGD. The relationship between the response to growth hormone therapy and pretreatment growth hormone secretory status.
Clin Endocrinol 1988; 28: 559-64.
Effect of famotidine
on
deficit symptoms of
schizophrenia SIR,-We report
a case
where the administration of famotidine,
prescribed for peptic ulcer disease, was associated with improvement in the deficit symptoms of schizophrenia. A 36-year-old man with a 15-year history of schizophrenia was admitted 1 year ago with an acute exacerbation. He was found to have formal thought disorder, paranoid ideation, social withdrawal, psychomotor retardation, and emotional blunting. In the 5 years before admission he lived alone in a dark room in his parents’ house, avoiding contact with others. He was not under the care of a psychiatrist, nor was he taking any medication. On the inpatient unit he was put on haloperidol and benztropine. His thought disorder and paranoid symptoms resolved in 3 weeks; however, severe extrapyramidal symptoms developed which were only marginally responsive to increased benztropine. Neuroleptic treatment had to be suspended and the patient was put on medication-free observation. His of deficit symptoms schizophrenia remained unchanged. A medical work-up during this time revealed symptomatic peptic ulcer disease. The patient was started on famotidine 40 mg daily 3 weeks after he stopped taking psychotropic medications. The deficit symptoms improved 10 days after initiation of famotidine. The patient became more sociable, verbal, and active, and within 2 months he could take part in a rehabilitation work programme. He was discharged on famotidine only with close follow-up.
