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Octreotide SIR,-We welcome your April 4 editorial, but it does contain an important error in reporting our data obtained in 41 acromegalic patients treated with octreotide. Growth hormone reduction takes place and mean values are less than 10 mU/1 (not 1 mU/1) in 55% of patients. This is a substantial difference since 1 mU/1 represents a cure but 10 mU/1 does not. Comparable figures for bromocriptine show that in 14% of acromegalics so treated, mean growth hormone values are less than 10 mU/U Growth hormone concentrations are 5 mU/1 or less in 32-5% of patients on octreotide and these values are associated with normal body composition .2 Octreotide does not necessarily need to be used life-long. If surgery is unsuccessful and there is persistent elevation of growth hormone concentrations above 5 mU/1, radiotherapy should be recommended. It is then that octreotide should be used until radiotherapy is effective. In most patients growth hormone concentrations gradually decrease, reaching values of 10 mU/1 between one and twelve years after its administration in 60% of

patients.3 Department of Endocrinology, St Bartholomew’s Hospital, London EC1A 7BE, UK

J. A. H. WASS G. M. BESSER

1. Wass JAH, Thorner MO, Morris DV, et al. Long-term treatment of acromegaly with bromocriptine. Br Med J 1977; 1: 875-78. 2. McLellan AR, Connell JMC, Beastall GH, Teasdale G, Davies DL. Growth hormone, body composition and somatomedin C after treatment of acromegaly. QJ Med 1988; 260: 997-1008. 3. Cicarelli E, Corsello SM, Ploughman TN, et al. Long-term effects of radiotherapy for acromegaly on circulating prolactin. Acta Endocrinol 1989; 121: 827-32.

Psychogenic vomiting SiR,—Your Feb 1 editorial points out that patients may have disorders of gastrointestinal motility as a result of psychological stress. Asthma is another disease that can be provoked by psychological stress. We report a case that demonstrates a connection between vomiting and asthma and extends the differential diagnoses of recurrent vomiting. At age 8 months this boy started to have severe vomiting every day for several weeks, accompanied by poor weight gain. Vomiting took place sometimes many hours after meals and occasionally during the night. It was sometimes preceded by trivial cough. At age 13 months he was admitted with fever, vomiting, and dehydration. Urinary infection was suspected but could not be verified. When he was 2 years old, urography, voiding cystography, and upper gastrointestinal radiography were done and proved normal. At 26 months he had symptoms of wheezing during exercise and 2 months later was diagnosed as having bronchial asthma. During this time vomiting was the main complaint. When &bgr;:.!-agonists were started vomiting disappeared, as did asthma. Vomiting and asthma recurred when this treatment was stopped, but disappeared when chromoglycic acid was introduced. Eight similar cases have been reported.1-3 In every case mild cough was present but was ignored because it seemed trivial in comparison with vomiting. Like our case, three of these eight patients also had associated atopic disorders and abnormal pulmonary tests which were reversed by bronchodilators. All patients were symptom-free when on bronchodilators or cromoglycic acid. Including our patient, eight of nine were boys and only one was adult when the vomiting started. From 1988 to 1991, 108 patients with unspecified vomiting were treated at the paediatric clinic at the community hospital in Karlstad, Sweden. Not one of these patients had a history in which there was a definite connection between vomiting and symptoms of asthma. Vomiting, as the only presenting symptom of asthma, is

probably rare. Schreir et al postulated neurological cross-connections between the vomiting and cough.centres in the medullaz through which afferent impulses via vagus into the cough centre could activate the vomiting centre. Alternatively, vomiting could be elicited by swallowed tenacious mucus that is seen in patients with lower respiratory tract infections.3 The prompt effect of &bgr;:.!-agonists and theophylline is evidence against gastro-oesophageal reflux as a primary event. Both these drugs have a tendency to exacerbate reflux.4 Autonomic nervous system abnormalities are common

among asthmatics,s and perhaps a general hyperreactivity in the lung and stomach is enough to explain why a trivial cough could lower the threshold and start an attack of what is often rather severe

vomiting. Barn-och ungdomsmedicinmottagningen. Vårdcentralen Gripen, Box 547, 651 12 Karlstad, Sweden

CARL-AXEL HEDEROS

1. Schreir L, Cutler RM, Saigal V. The vomiting asthmatic. Ann Allergy 1984; 53: 42-44. 2. Schreir L, Cutler RM, Saigal V. Vomiting as a dominant symptom of asthma. Ann Allergy 1987; 58: 118-20 3. Osundwa VM, Dawod ST. Vomiting as the main presenting symptom of acute asthma. Acta Paediatr Scand 1989; 78: 968-70. 4. Simpson H, Hampton F. Gastro-oesophageal reflux and the lung. Arch Dis Child 1991; 66: 277-83. 5. Kaliner M. Autonomic nervous system abnormalities and allergy. Ann Intern Med

1982; 96: 349-57.

Imprinting and Beckwith-Wiedemann syndrome SiR,—Mr Fidler and colleagues (Jan 25, p 243) suggest a trans-sensing hypothesis to explain the origin of the BeckwithWiedemann syndrome (BWS). They propose that the homologous insulin-like growth factor Igf2 genes are paired in mitotic cells and that the maternal allele acts directly as a suppressor of the expression of a paternal Igf2 allele. Disruption of the physical pairing would cause a deregulation and result in an abnormal phenotype. We feel that this model does not accord with experimental data. First, all mothers of BWS patients with balanced rearrangements are phenotypically normal, although they carry exactly the same translocation or inversion. If gene deregulation was due to a disturbed ability of the Igf2 alleles to pair, because of the rearrangement, the mothers should also be affected. The same holds true for patients. Second, although the breakpoints in the BWS cases with a paternally derived trisomy for llp15are heterogeneous (varying from llpl4.2 to llpl5.4), the breakpoints in the maternally inherited translocations are in two distinct clusters in l lp15.4 and 1 lpl5.5, both proximal to Igf2 Y- Because the Igf2 gene itself is not disrupted, these observations strongly suggest the involvement of multiple loci in the aetiology of BWS. Finally, loss of heterozygosity (LOH) studies have demonstrated that loss of maternal alleles in llpl5 in some Wilms’ tumours is limited to a region at llpl5 proximal to HBBC (and therefore not involving Igf2). This region coincides with the proximal breakpoint cluster in BWS 2 We believe that an imprinting model involving multiple loci is sufficient to explain the present molecular and cytogenetic data on BWS. We propose that there are at least two loci on llpl5 that show opposite parental imprinting: Igf2 with expression of the paternal allele only and one or more cis and/or transacting suppressor gene(s) of Igf2 with expression of the maternal allele only. Usually there is one active (maternal) suppressor and one active (paternal) Igf2 allele. Mutations leading to BWS can be explained by inactivation of the maternal suppressor or activation of the maternal Igf2, both leading to overexpression of Igf2. Paternal disomy results in two inactive suppressor genes and/or two active Igf2 alleles, whereas in tumours the active (maternal) suppressor gene has been lost. In BWS patients with paternally derived trisomies there is an extra paternal Igf2 copy. The normal phenotype of fathers with a balanced rearrangement can be explained by the fact that all genes are correctly imprinted. The same is true for the mothers with a balanced rearrangement. We assume that, because of the rearrangement, the correct imprint is disturbed during oogenesis, resulting in an inactive suppressor or active maternal Igf2 allele, or both, in the child .2

Institute of Human Genetics, University of Amsterdam, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands

J. M. N. HOOVERS A. J. J. DIETRICH M. M. A. M. MANNENS

1. Mannens M, Hoovers JMN, Redeker B, et al. Characterization of breakpoints associated with Beckwith-Wiedemann syndrome and aniridia: evidence for involvement of genomic imprinting in the Beckwith-Wiedemann syndrome. Am J Hum Genet 1991; 49 (suppl): 148. 2. Mannens M. The molecular genetics of Wilm’s tumour and associated congenital diseases. Thesis, University of Amsterdam, 1991.

Psychogenic vomiting.

1228 Octreotide SIR,-We welcome your April 4 editorial, but it does contain an important error in reporting our data obtained in 41 acromegalic patie...
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