Rectal gluten challenge and diagnosis of coeliac disease
1
570 Distribution of weight at age 54 months by birthweight (upper) and of severe cerebral palsy within growth centiles (lower). Upper fig n = 553; lower n = 603 for head circumference, n = 604 for height, n = 553 for weight. We therefore examined the association between severe neuromotor involvement and later weight, independent of birthweight, with GLIM.3 The prediction equation (weight [kg] = - 45-27 + 7-468 log [age in years] +7-214 tog [birthweight in g]+003176 gestation2 [in completed weeks]-0-004703 log [birthweight] gestation2) suggested that the more severe form of motor deficit was associated with a small weight loss (about 1-6 kg, 95% confidence intervals [CI] 0-7 to 2-6), although children who were less severely disabled were slightly heavier and taller than children of the same birthweight without motor problems (0-7 kg, 95 % CI - 02 to 1-6). Those who had a neuromotor impairment without disability were very slightly lighter (0-2 kg, 95% CI -1-0 to 0-5) at 4t years than the remainder of this low-birthweight population. The addition to the model of factors that might affect the ability to self-feed such as the dominant lesion affecting the upper arm and hand function, or daytime drooling, did not improve the power of the model to predict later weight. Blind children were lighter than their peers, independent of whether or not they had cerebral palsy. The overall predictive power of the model was not impressive (RI = 12 %), but the population we describe was not normal with respect to birthweight. It is noteworthy that 25% of children with heights below the 3rd centile had severe cerebral palsy at age 42 years. Their mean maternal and paternal heights did not differ from those of low-birthweight children who did not have cerebral palsy-and this was true at all birthweights under 1750 g. It would seem therefore that in low-birthweight children there is a significant, but clinically small, reduction in weight at age 41 that is independent of birthweight only in the most severely affected children. The pattern of growth in these children is probably more complex than your editorial suggests. It may indeed be an inherent feature of the underlying developmental insult of which cerebral palsy is also a manifestation. Social Paediatric and Obstetric Research Unit, University of Glasgow, Glasgow G1 2 8RZ, UK LESLEY MUTCH ALASTAIR LEYLAND 1. McIlwaine G, Mutch L, Pritchard C, Fletcher V. The Scottish low birthweight study- the pregnancies, neonatal progress and outcome at two years. Report to the Scottish Home and Health Department, 1989. 2. Amiel Tison C, Stewart AL. Follow up studies in the first five years of life: a pervasive assessment of neurological function. Arch Dis Child 1989; 64: 496-502 3. Baker RJ, Nelder JA. The GLIM system, release 3. generalised linear interactive modelling. Oxford: Numerical Algorithms Group, 1978. Rectal gluten challenge and diagnosis of coeliac disease SIR,-We wish to clarify some of the issues raised by Dr Smith and Dr Dallimore, and Dr Gilvarry and Dr Fielding (June 30, p 1592) about our study (June 2, p 1293). Gilvarry and Fielding should not have been surprised by our inclusion of two patients with ileal Crohn’s disease. Ours was a prospective study of patients referred consecutively for jejunal biopsy: we were not entitled to exclude any individuals from subsequent analysis. Jejunal biopsy and rectal gluten challenges were done on the same day and the diagnosis was established by "gold standard" jejunal biopsy criteria: any later exclusions would have invalidated the study. The two patients with ileal Crohn’s disease did not respond to gluten challenge. The two false-positives, as stated in our paper, were a 71-year-old woman with diarrhoea and microscopic colitis and a 34-year-old man with aphthous ulceration and no other gastrointestinal complaints. Since intraepithelial lymphocytes have not previously been shown to be raised in inflammatory bowel disease," we await with interest to see if Gilvarry and Fielding’s findings will confirm or refute these studies, and how they will interpret their results. We are intrigued that Smith and Dallimore consider upper intestinal endoscopy and biopsy aesthetically preferable to rectal gluten challenge. Our patients did not find the rectal procedure arduous or unacceptable, and some returned to work after the first biopsy, attending 6 h later for repeat biopsy. Since none of our 44 subjects refused this experimental protocol we wonder if the same compliance could be achieved from a prospective endoscopic study, and if patients would share the same enthusiasm for intubation as do their doctors? In general our patients showed interest (and relief) in this novel, non-oral approach. Finally, our study was not concerned with the comparative merits of jejunal and endoscopic duodenal biopsy in the diagnosis of gluten sensitivity. Department of Gastroenterology and Nutrition, Central Middlesex Hospital, London NW10 7NS, UK DUNCAN E. LOFT University Department of Medicine, Hope Hospital, Salford MICHAEL N. MARSH PETER T. CROWE 1. Meuwissen SGM, Feltkamp-Vroom TM, Brutel De La Riviere A, Von Dem Borne AEG, Tytgat GN. Analysis of lympho-plasmacytic infiltrate in Crohn’s disease with special reference to identification of lymphocyte-subpopulations. Gut 1976; 17: 770-80. 2. Selby WS, Janossy G, Bofill M, Jewell DP. Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques. Gut 1984; 25: 32-40. 3. Dobbins WO. Human intestinal intraepithelial lymphocytes. Gut 1986; 27: 972-85 4. Hirata I, Berrebi G, Austin LL, Keren DF, Dobbins WO. Immunohistological characterization of intraepithelial and lamina propria lymphocytes in control ileum and colon and in inflammatory bowel disease. Dig Dis Sci 1986; 31: 593-603. Antibodies to thymic hormone and HLA-DQ in type I diabetes SIR,-Recent evidence from animal models has suggested that thymic T-cell maturation may be aberrant in type I diabetes.!) In the mutant diabetic (db/db) mouse, thymic dysfunction was accompanied by the production of antibodies to serum thymic factor. 3,4 We describe the presence in sera from patients with type I diabetes of antibodies binding both serum thymic factor and HLA-DQ &bgr;-chain determinants. Using an ELI SA method we tested sera from 116 patients with recent onset type I diabetes (age range 5-63 years, 55% males, all islet cell antibody-positive) and 108 healthy blood donors (age range 19-54 years, kindly provided by Prof J. Bertrams, Elisabeth Hospital, Essen). Sera were initially screened for antibodies against aminoacid-57-associated peptide region 53-62 of the HLA-DQw8 P chain. Antibodies were found in 23 (19-8%) patient sera compared with 3 (2-8%) normal sera (p < 0-001, chi-square test).1 t of the positive normal sera contained IgM antibodies and the other 2 contained IgG antibodies. Of 19 patient sera, 9 contained IgM antibodies, 8 contained IgG antibodies and 2 contained both
Transcript of Rectal gluten challenge and diagnosis of coeliac disease
570
Distribution of weight at age 54 months by birthweight (upper)and of severe cerebral palsy within growth centiles (lower).
Upper fig n = 553; lower n = 603 for head circumference, n = 604 forheight, n = 553 for weight.
We therefore examined the association between severe
neuromotor involvement and later weight, independent of
birthweight, with GLIM.3 The prediction equation (weight[kg] = - 45-27 + 7-468 log [age in years] +7-214 tog [birthweight ing]+003176 gestation2 [in completed weeks]-0-004703 log[birthweight] gestation2) suggested that the more severe form ofmotor deficit was associated with a small weight loss (about 1-6 kg,95% confidence intervals [CI] 0-7 to 2-6), although children whowere less severely disabled were slightly heavier and taller thanchildren of the same birthweight without motor problems (0-7 kg,95 % CI - 02 to 1-6). Those who had a neuromotor impairmentwithout disability were very slightly lighter (0-2 kg, 95% CI -1-0 to0-5) at 4t years than the remainder of this low-birthweightpopulation. The addition to the model of factors that might affectthe ability to self-feed such as the dominant lesion affecting theupper arm and hand function, or daytime drooling, did not improvethe power of the model to predict later weight. Blind children werelighter than their peers, independent of whether or not they hadcerebral palsy.The overall predictive power of the model was not impressive
(RI = 12 %), but the population we describe was not normal withrespect to birthweight. It is noteworthy that 25% of children withheights below the 3rd centile had severe cerebral palsy at age 42years. Their mean maternal and paternal heights did not differ fromthose of low-birthweight children who did not have cerebralpalsy-and this was true at all birthweights under 1750 g.
It would seem therefore that in low-birthweight children there isa significant, but clinically small, reduction in weight at age 41 that isindependent of birthweight only in the most severely affectedchildren. The pattern of growth in these children is probably morecomplex than your editorial suggests. It may indeed be an inherentfeature of the underlying developmental insult of which cerebralpalsy is also a manifestation.
Social Paediatric and Obstetric Research Unit,University of Glasgow,Glasgow G1 2 8RZ, UK
LESLEY MUTCHALASTAIR LEYLAND
1. McIlwaine G, Mutch L, Pritchard C, Fletcher V. The Scottish low birthweight study-the pregnancies, neonatal progress and outcome at two years. Report to the ScottishHome and Health Department, 1989.
2. Amiel Tison C, Stewart AL. Follow up studies in the first five years of life: a pervasiveassessment of neurological function. Arch Dis Child 1989; 64: 496-502
3. Baker RJ, Nelder JA. The GLIM system, release 3. generalised linear interactivemodelling. Oxford: Numerical Algorithms Group, 1978.
Rectal gluten challenge and diagnosis ofcoeliac disease
SIR,-We wish to clarify some of the issues raised by Dr Smith andDr Dallimore, and Dr Gilvarry and Dr Fielding (June 30, p 1592)about our study (June 2, p 1293).
Gilvarry and Fielding should not have been surprised by ourinclusion of two patients with ileal Crohn’s disease. Ours was aprospective study of patients referred consecutively for jejunalbiopsy: we were not entitled to exclude any individuals fromsubsequent analysis. Jejunal biopsy and rectal gluten challengeswere done on the same day and the diagnosis was established by"gold standard" jejunal biopsy criteria: any later exclusions wouldhave invalidated the study. The two patients with ileal Crohn’sdisease did not respond to gluten challenge. The two false-positives,as stated in our paper, were a 71-year-old woman with diarrhoeaand microscopic colitis and a 34-year-old man with aphthousulceration and no other gastrointestinal complaints. Since
intraepithelial lymphocytes have not previously been shown to beraised in inflammatory bowel disease," we await with interest to seeif Gilvarry and Fielding’s findings will confirm or refute thesestudies, and how they will interpret their results.We are intrigued that Smith and Dallimore consider upper
intestinal endoscopy and biopsy aesthetically preferable to rectalgluten challenge. Our patients did not find the rectal procedurearduous or unacceptable, and some returned to work after the firstbiopsy, attending 6 h later for repeat biopsy. Since none of our 44subjects refused this experimental protocol we wonder if the samecompliance could be achieved from a prospective endoscopic study,and if patients would share the same enthusiasm for intubation as dotheir doctors? In general our patients showed interest (and relief) inthis novel, non-oral approach. Finally, our study was not concernedwith the comparative merits of jejunal and endoscopic duodenalbiopsy in the diagnosis of gluten sensitivity.
Department of Gastroenterologyand Nutrition,
Central Middlesex Hospital,London NW10 7NS, UK DUNCAN E. LOFT
University Department of Medicine,Hope Hospital, Salford
MICHAEL N. MARSHPETER T. CROWE
1. Meuwissen SGM, Feltkamp-Vroom TM, Brutel De La Riviere A, Von Dem BorneAEG, Tytgat GN. Analysis of lympho-plasmacytic infiltrate in Crohn’s diseasewith special reference to identification of lymphocyte-subpopulations. Gut 1976;17: 770-80.
2. Selby WS, Janossy G, Bofill M, Jewell DP. Intestinal lymphocyte subpopulations ininflammatory bowel disease: an analysis by immunohistological and cell isolationtechniques. Gut 1984; 25: 32-40.
3. Dobbins WO. Human intestinal intraepithelial lymphocytes. Gut 1986; 27: 972-854. Hirata I, Berrebi G, Austin LL, Keren DF, Dobbins WO. Immunohistological
characterization of intraepithelial and lamina propria lymphocytes in control ileumand colon and in inflammatory bowel disease. Dig Dis Sci 1986; 31: 593-603.
Antibodies to thymic hormone and HLA-DQin type I diabetes
SIR,-Recent evidence from animal models has suggested thatthymic T-cell maturation may be aberrant in type I diabetes.!) Inthe mutant diabetic (db/db) mouse, thymic dysfunction wasaccompanied by the production of antibodies to serum thymicfactor. 3,4 We describe the presence in sera from patients with type Idiabetes of antibodies binding both serum thymic factor andHLA-DQ &bgr;-chain determinants.
Using an ELI SA method we tested sera from 116 patients withrecent onset type I diabetes (age range 5-63 years, 55% males, allislet cell antibody-positive) and 108 healthy blood donors (age range19-54 years, kindly provided by Prof J. Bertrams, ElisabethHospital, Essen). Sera were initially screened for antibodies againstaminoacid-57-associated peptide region 53-62 of the HLA-DQw8P chain. Antibodies were found in 23 (19-8%) patient sera
compared with 3 (2-8%) normal sera (p < 0-001, chi-square test).1 tof the positive normal sera contained IgM antibodies and the other 2contained IgG antibodies. Of 19 patient sera, 9 contained IgMantibodies, 8 contained IgG antibodies and 2 contained both
