- Email: [email protected]
COELIAC DISEASE AS CAUSE OF PROTRACTED DIARRHOEA IN INDIAN CHILDREN
126 IMPROVING THE EFFICIENCY OF DRUG
ADMINISTRATION WITH JET NEBULISERS SiR,—The apparatus currently used to inhale aerosol produced by jet nebulisers is inefficient since almost all aerosol produced when the patient is not inhaling is wasted to the atmosphere. Since inhalation takes up only a small part of the respiratory cycle, this loss is considerable. We describe two inhalation manifolds designed to reduce waste by incorporating a storage chamber that retains aerosol produced during exhalation for delivery to the mouthpiece at the following inhalation. The ’Mist Mizer’ (Medicaid) is comniercially available but not widely used (figure). Attempts to overcome two of its potential disadvantages-loss of aerosol from the storage chamber to the atmosphere and deposition of aerosol on the valve between storage chamber and mouthpiece-led to the production of an airtight aerosol saving manifold (AASM) (figure). The
efficacy of these manifolds was assessed with standard apparatus (figure) in six healthy volunteers as a control. Radioaerosol was produced by an acorn nebuliser (Medicaid) filled with 7 ml 99mTc-labelled colloidal human aggregate and driven by an airflow of 61/min, and inhaled for 3 min via each apparatus in random order. Appearance of isotope in the lungs was measured by dynamic scintiscanning with a gamma camera. From these data, activity-time curves were constructed and the slopes of these, calculated by computer, were used as a measure of pulmonary aerosol deposition rate (PADR). Because identical aerosol was used in each experiment, these values reflect the efficiency of the inhalation apparatus. Subject ventilation and mouthpiece pC02 were monitored during the experiments by impedance plethysmography and capnometry. Escape of isotope to the atmosphere was prevented by filters placed over the inhalation and exhalation parts of each apparatus. After each experiment, the counts retained in each filter were measured to assess the amount of aerosol that would be lost to the atmosphere. The results are shown in the table. The mist mizer and the AASM promoted faster PADR than standard apparatus both in the lungs overall and in peripheral lung (outer third of both lungs), and loss of aerosol to the atmosphere (deposited in inhalation/exhalation filters) was reduced. No significant changes in mouthpiece pC02 or ventilation were observed. The improvements demonstrated with these manifolds have two possible benefits. The AASM allows a financial saving of almost
50%, amounting to about £1000 in the annual cost of aerosol gentamicin and carbenicillin therapy. Alternatively, the time required for each treatment could be reduced, encouraging better patient compliance. S. H. L. THOMAS*
J. A. LANGFORD London Chest London E2
R. D. G. GEORGE D. M. GEDDES
Hospital,
*Present address: Department of
Pharmacology,
St Thomas’
Hospital, London SE1
7EH
COELIAC DISEASE AS CAUSE OF PROTRACTED DIARRHOEA IN INDIAN CHILDREN
SIR,- There have been few reports from developing countries on the diagnosis of coeliac disease (CD) in children.’-, In a report from north Indial the diagnosis was based on jejunal biopsy and response to a gluten-free diet and was thus not specific. Similar diagnostic criteria were used to identify CD in children of Asian immigrants in the UK.3 It is important to establish whether or not CD is found in India because chronic diarrhoea is a major cause of mortality in a population where the treatment of acute diarrhoea with oral rehydration solutions is widespread.4 We have studied the prevalence of CD in Indian children using the criteria of the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN),5—ie, demonstration of clinical and histological response to gluten withdrawal and subsequent histological relapse after gluten provocation. We studied 100 randomly selected children under the age of 5 years who presented with diarrhoea lasting more than 21 days and failure to thrive, to the paediatric gastroenterology unit, All India Institute of Medical Sciences, over 12 months in 1983-84. Detailed stool examinationsb were done to exclude enteropathogens, including Giardia lamblia. Positive anti-reticulin antibodies (ARA) and serum anti-gliadin antibodies (AGA) were considered supportive evidence for CD. 22 patients had evidence of a severe mucosal injury but only 5 met ESPGAN criteria. The mean age at onset of symptoms in these 5 children was 12-2 (SD 4-4) months (range 7-18) and the mean duration of symptoms before admission was 29 (SD 14) months (range 12-46). All the children were on cow’s milk but this was not
RESULTS
127 BIOPSY FINDINGS IN 5 INDIAN CHILDREN WITH COELIAC DISEASE
PSYCHIATRIC DAY HOSPITALS
withdrawn, the only dietary manipulation being withdrawal of gluten. Villous height and crypt zone depth ratios in untreated disease, after 12 months of gluten withdrawal, and after 1 month of
SIR,-We agree with your Nov 21 editorial (p 1184) on psychiatric day hospitals that mixing neurotic and psychotic patients is not helpful. At Bexiey we are planning a new type of service to deal with exactly this problem. The plan, at Upton Road Day Hospital, Bexleyheath, is to separate the two groups and offer each the type of treatment patients are most likely to respond to. We cannot afford two day hospitals but, with flexibility and dedication of the day hospital’s staff, it was agreed to work two different shifts on some-serving one population from 0900 hours to 1700 and another from 1700 to 2100. This means not only that the two different day-hospital populations would receive appropriate help but also that the staff skills and the hospital premises will be fully utilised and that some treatment will be available after 1700 hours, which may attract patients with daytime jobs who might otherwise
shown in the table. All 5 patients had a flat jejunal biopsy. The mucosa improved after gluten withdrawal, with relief of diarrhoea and abdominal discomfort, a gain of over 50% of initial body weight, and improved height, appetite, and behaviour. All 5 children showed a histological relapse after 1 month of gluten reintroduction. Stool analysis in patients developing diarrhoea was repeated to exclude concurrent infection with enteric pathogens; all were negative. Symptoms disappeared on repeat withdrawal of gluten, and a fourth jejunal biopsy, done after 12 months, showed a near-normal mucosa. All 5 patients initially had high titres of serum AGA (both IgA and IgG) which became normal within 3 months after strict gluten withdrawal from the diet and rose on reintroduction of gluten. 3 patients had a positive ARA showing the typical pattern (R-1); a fourth showed an atypical pattern (R-2) .7 In these Indian children the symptoms of CD appeared later than they do in Western children with this illness, probably because of delayed weaning and the late introduction of gluten. All the patients had moderate to severe protein-energy malnutrition, having been brought to hospital 1-4 years after onset, and the diagnosis had not been considered by general practitioners. There was a slow histological recovery (table), possibly because of malnutrition, increased small-bowel bacterial flora, or poor dietary compliance (though diet was carefully monitored and repeat AGA estimations were negative). Intolerance to soy has been associated with a poor response to gluten withdrawal in patients with CD8 but none of these 5 children had ever taken soy. Coeliac disease is therefore one cause of protracted diarrhoea in Indian children and its existence in developing countries should not be overlooked, even though a decrease in its incidence is being reported in developing countries.9
gluten challenge mucosa on
are
Department of Paediatrics, Division of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
V. KHOSHOO M. K. BHAN R. JAIN
Queen Elizabeth Hospital for Children, London E2 8PS
A. D. PHILLIPS J. A. WALKER-SMITH
St Bartholomew’s Hospital, London EC1
D.
St Gorans Hospital, Karolinska Institute, Stockholm, Sweden
G. STINTZING
1 Walia
BNS, Signu JK, Tandon BN, Br Med J 1966, ii: 1233-34
et
al Coeliac disease
J. UNSWORTH
in
North Indian children.
2 Sulimon GI. Coeliac disease in Sudanese children Gut 1978; 19: 121-25 3 Nelson R, McNeish AS, Anderson CM Coeliac disease in children of Asian
immigrants. Lancet 1973; i: 348-50. MK, Arora NK, Ghai OP, et al. Major factors in diarrhoea related mortality among rural children. Indian JMed Res 1986, 83: 9-12. Meeuwisse G Diagnostic criteria in coeliac disease Acta Paediatr Scand 1970; 59:
4 Bhan 5
be excluded.
the first
461-63. 6 World Health
Organisation. Manual for laboratory investigations of acute enteric infections (WHO CDD 1983; 83 3). Geneva WHO, 1983. 7 Rizetto M, Doniach D Types of reticulin antibodies detected m human sera by immunofluorescence. J Clin Pathol 1973, 26: 841-45 8. Haeney MR, Goodwin BJF, Barratt MEJ, et al. Soya protein antibodies in man: their occurrence and possible relevance in coeliac disease J Clin Pathol 1982, 35: 319-32. 9. Stevens FM, Egan-Mitchell B, Cryan E, McCarthy CF, McNicholl B Decreasing incidence of coeliac disease Arch Dis Child 1987, 62: 465-68
Bexley Hospital, Bexley, Kent DA5 2BW
BASEM T. FARID
J. M. HIRONS
LONGSTANDING INFECTION WITH SCHISTOSOMA MANSONI
SIR,—Schistosomal infections can remain active for many years, despite the fact that adult worms do not replicate within the human host. With all species of human schistosome the adult can live as long as 25 years, although in endemic areas 2-5 years is normal.’ We report two cases with very long durations of activity, 32 and 23 years.
A 46-year-old man (66 kg of European parentage left Uganda, where he had been born, for the UK during his childhood and had not travelled outside Europe since. 32 years later he complained of pruritus ani. Mild hepatosplenomegaly, confirmed by ultrasonography, was detected; sigmoidoscopy was normal. He excreted 11 6x 103 viable ova of Schistosoma ntansom in 24 h; schistosomal ELISA serology was positive. Serum immunoglobulins and biochemical tests of liver function, apart from a raised alkaline phosphatase (142 IU 1B were normal. Needle liver-biopsy revealed a eosinophilic infiltration, with mild portal fibrosis and a granuloma surrounding an S mustsoui egg. Barium swallow was normal. A 39-year-old Asian woman (53 kg) born m Calcutta, India, lived in Uganda for 13 years. For the next 23 years she lived in the UK and had travelled only to Bengal. During a "tropical screen", schistosomal ELISA serology was found to be positive. Viable S mansom ova were demonstrable in several faecal samples. In neither case was a peripheral blood eosinophilia detected, both patients were treated successfully with oral praziquantel. Hospital for Tropical Diseases, London NW1 0PE
G. C. COOK A. D. M. BRYCESON
LW Schistosomiasis In Strickland G T, ed Hunter’s tropical medicine, 6th ed London: Saunders, 1984 708-40 2 Manson-Bahr PEC, Apted FIC Manson’s tropical diseases, 18th ed London Bailliere Tindall, 1982 206-28 3. Muller R Worms and disease a manual of medical helminthology London Heinemann, 1975 12 1
Laughlin
H2-RECEPTOR ANTAGONIST NON-RESPONDERS SIR,--Our findings (to be published in Alimentary, Plaarrnacology and Therapeutics) are not entirely in agreement with those of Dr Savarino and his colleagues (Nov 28, p 1281). We treated 32 patients with endoscopically proven duodenal ulcer with cimetidine 400 mg twice daily for 6 weeks. Overnight gastric secretion was measured before and during treatment. In 12 patients the ulcers did not heal and they had less profound inhibition of overnight acidity than those with healed ulcers p<0’01). This fits in with what Savarino et al and others have found.1.2 However, 2 patients’ ulcers failed to heal despite achlorhydria overnight on treatment. Tablet counts revealed no evidence of non-compliance. 9 of these 12 non-healers consented to further secretion studies while on cimetidine 400 mg with pirenzepme 50 mg and on cimetidine 1600 mg. Both treatments were significantly better at ,
ADMINISTRATION WITH JET NEBULISERS SiR,—The apparatus currently used to inhale aerosol produced by jet nebulisers is inefficient since almost all aerosol produced when the patient is not inhaling is wasted to the atmosphere. Since inhalation takes up only a small part of the respiratory cycle, this loss is considerable. We describe two inhalation manifolds designed to reduce waste by incorporating a storage chamber that retains aerosol produced during exhalation for delivery to the mouthpiece at the following inhalation. The ’Mist Mizer’ (Medicaid) is comniercially available but not widely used (figure). Attempts to overcome two of its potential disadvantages-loss of aerosol from the storage chamber to the atmosphere and deposition of aerosol on the valve between storage chamber and mouthpiece-led to the production of an airtight aerosol saving manifold (AASM) (figure). The
efficacy of these manifolds was assessed with standard apparatus (figure) in six healthy volunteers as a control. Radioaerosol was produced by an acorn nebuliser (Medicaid) filled with 7 ml 99mTc-labelled colloidal human aggregate and driven by an airflow of 61/min, and inhaled for 3 min via each apparatus in random order. Appearance of isotope in the lungs was measured by dynamic scintiscanning with a gamma camera. From these data, activity-time curves were constructed and the slopes of these, calculated by computer, were used as a measure of pulmonary aerosol deposition rate (PADR). Because identical aerosol was used in each experiment, these values reflect the efficiency of the inhalation apparatus. Subject ventilation and mouthpiece pC02 were monitored during the experiments by impedance plethysmography and capnometry. Escape of isotope to the atmosphere was prevented by filters placed over the inhalation and exhalation parts of each apparatus. After each experiment, the counts retained in each filter were measured to assess the amount of aerosol that would be lost to the atmosphere. The results are shown in the table. The mist mizer and the AASM promoted faster PADR than standard apparatus both in the lungs overall and in peripheral lung (outer third of both lungs), and loss of aerosol to the atmosphere (deposited in inhalation/exhalation filters) was reduced. No significant changes in mouthpiece pC02 or ventilation were observed. The improvements demonstrated with these manifolds have two possible benefits. The AASM allows a financial saving of almost
50%, amounting to about £1000 in the annual cost of aerosol gentamicin and carbenicillin therapy. Alternatively, the time required for each treatment could be reduced, encouraging better patient compliance. S. H. L. THOMAS*
J. A. LANGFORD London Chest London E2
R. D. G. GEORGE D. M. GEDDES
Hospital,
*Present address: Department of
Pharmacology,
St Thomas’
Hospital, London SE1
7EH
COELIAC DISEASE AS CAUSE OF PROTRACTED DIARRHOEA IN INDIAN CHILDREN
SIR,- There have been few reports from developing countries on the diagnosis of coeliac disease (CD) in children.’-, In a report from north Indial the diagnosis was based on jejunal biopsy and response to a gluten-free diet and was thus not specific. Similar diagnostic criteria were used to identify CD in children of Asian immigrants in the UK.3 It is important to establish whether or not CD is found in India because chronic diarrhoea is a major cause of mortality in a population where the treatment of acute diarrhoea with oral rehydration solutions is widespread.4 We have studied the prevalence of CD in Indian children using the criteria of the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN),5—ie, demonstration of clinical and histological response to gluten withdrawal and subsequent histological relapse after gluten provocation. We studied 100 randomly selected children under the age of 5 years who presented with diarrhoea lasting more than 21 days and failure to thrive, to the paediatric gastroenterology unit, All India Institute of Medical Sciences, over 12 months in 1983-84. Detailed stool examinationsb were done to exclude enteropathogens, including Giardia lamblia. Positive anti-reticulin antibodies (ARA) and serum anti-gliadin antibodies (AGA) were considered supportive evidence for CD. 22 patients had evidence of a severe mucosal injury but only 5 met ESPGAN criteria. The mean age at onset of symptoms in these 5 children was 12-2 (SD 4-4) months (range 7-18) and the mean duration of symptoms before admission was 29 (SD 14) months (range 12-46). All the children were on cow’s milk but this was not
RESULTS
127 BIOPSY FINDINGS IN 5 INDIAN CHILDREN WITH COELIAC DISEASE
PSYCHIATRIC DAY HOSPITALS
withdrawn, the only dietary manipulation being withdrawal of gluten. Villous height and crypt zone depth ratios in untreated disease, after 12 months of gluten withdrawal, and after 1 month of
SIR,-We agree with your Nov 21 editorial (p 1184) on psychiatric day hospitals that mixing neurotic and psychotic patients is not helpful. At Bexiey we are planning a new type of service to deal with exactly this problem. The plan, at Upton Road Day Hospital, Bexleyheath, is to separate the two groups and offer each the type of treatment patients are most likely to respond to. We cannot afford two day hospitals but, with flexibility and dedication of the day hospital’s staff, it was agreed to work two different shifts on some-serving one population from 0900 hours to 1700 and another from 1700 to 2100. This means not only that the two different day-hospital populations would receive appropriate help but also that the staff skills and the hospital premises will be fully utilised and that some treatment will be available after 1700 hours, which may attract patients with daytime jobs who might otherwise
shown in the table. All 5 patients had a flat jejunal biopsy. The mucosa improved after gluten withdrawal, with relief of diarrhoea and abdominal discomfort, a gain of over 50% of initial body weight, and improved height, appetite, and behaviour. All 5 children showed a histological relapse after 1 month of gluten reintroduction. Stool analysis in patients developing diarrhoea was repeated to exclude concurrent infection with enteric pathogens; all were negative. Symptoms disappeared on repeat withdrawal of gluten, and a fourth jejunal biopsy, done after 12 months, showed a near-normal mucosa. All 5 patients initially had high titres of serum AGA (both IgA and IgG) which became normal within 3 months after strict gluten withdrawal from the diet and rose on reintroduction of gluten. 3 patients had a positive ARA showing the typical pattern (R-1); a fourth showed an atypical pattern (R-2) .7 In these Indian children the symptoms of CD appeared later than they do in Western children with this illness, probably because of delayed weaning and the late introduction of gluten. All the patients had moderate to severe protein-energy malnutrition, having been brought to hospital 1-4 years after onset, and the diagnosis had not been considered by general practitioners. There was a slow histological recovery (table), possibly because of malnutrition, increased small-bowel bacterial flora, or poor dietary compliance (though diet was carefully monitored and repeat AGA estimations were negative). Intolerance to soy has been associated with a poor response to gluten withdrawal in patients with CD8 but none of these 5 children had ever taken soy. Coeliac disease is therefore one cause of protracted diarrhoea in Indian children and its existence in developing countries should not be overlooked, even though a decrease in its incidence is being reported in developing countries.9
gluten challenge mucosa on
are
Department of Paediatrics, Division of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
V. KHOSHOO M. K. BHAN R. JAIN
Queen Elizabeth Hospital for Children, London E2 8PS
A. D. PHILLIPS J. A. WALKER-SMITH
St Bartholomew’s Hospital, London EC1
D.
St Gorans Hospital, Karolinska Institute, Stockholm, Sweden
G. STINTZING
1 Walia
BNS, Signu JK, Tandon BN, Br Med J 1966, ii: 1233-34
et
al Coeliac disease
J. UNSWORTH
in
North Indian children.
2 Sulimon GI. Coeliac disease in Sudanese children Gut 1978; 19: 121-25 3 Nelson R, McNeish AS, Anderson CM Coeliac disease in children of Asian
immigrants. Lancet 1973; i: 348-50. MK, Arora NK, Ghai OP, et al. Major factors in diarrhoea related mortality among rural children. Indian JMed Res 1986, 83: 9-12. Meeuwisse G Diagnostic criteria in coeliac disease Acta Paediatr Scand 1970; 59:
4 Bhan 5
be excluded.
the first
461-63. 6 World Health
Organisation. Manual for laboratory investigations of acute enteric infections (WHO CDD 1983; 83 3). Geneva WHO, 1983. 7 Rizetto M, Doniach D Types of reticulin antibodies detected m human sera by immunofluorescence. J Clin Pathol 1973, 26: 841-45 8. Haeney MR, Goodwin BJF, Barratt MEJ, et al. Soya protein antibodies in man: their occurrence and possible relevance in coeliac disease J Clin Pathol 1982, 35: 319-32. 9. Stevens FM, Egan-Mitchell B, Cryan E, McCarthy CF, McNicholl B Decreasing incidence of coeliac disease Arch Dis Child 1987, 62: 465-68
Bexley Hospital, Bexley, Kent DA5 2BW
BASEM T. FARID
J. M. HIRONS
LONGSTANDING INFECTION WITH SCHISTOSOMA MANSONI
SIR,—Schistosomal infections can remain active for many years, despite the fact that adult worms do not replicate within the human host. With all species of human schistosome the adult can live as long as 25 years, although in endemic areas 2-5 years is normal.’ We report two cases with very long durations of activity, 32 and 23 years.
A 46-year-old man (66 kg of European parentage left Uganda, where he had been born, for the UK during his childhood and had not travelled outside Europe since. 32 years later he complained of pruritus ani. Mild hepatosplenomegaly, confirmed by ultrasonography, was detected; sigmoidoscopy was normal. He excreted 11 6x 103 viable ova of Schistosoma ntansom in 24 h; schistosomal ELISA serology was positive. Serum immunoglobulins and biochemical tests of liver function, apart from a raised alkaline phosphatase (142 IU 1B were normal. Needle liver-biopsy revealed a eosinophilic infiltration, with mild portal fibrosis and a granuloma surrounding an S mustsoui egg. Barium swallow was normal. A 39-year-old Asian woman (53 kg) born m Calcutta, India, lived in Uganda for 13 years. For the next 23 years she lived in the UK and had travelled only to Bengal. During a "tropical screen", schistosomal ELISA serology was found to be positive. Viable S mansom ova were demonstrable in several faecal samples. In neither case was a peripheral blood eosinophilia detected, both patients were treated successfully with oral praziquantel. Hospital for Tropical Diseases, London NW1 0PE
G. C. COOK A. D. M. BRYCESON
LW Schistosomiasis In Strickland G T, ed Hunter’s tropical medicine, 6th ed London: Saunders, 1984 708-40 2 Manson-Bahr PEC, Apted FIC Manson’s tropical diseases, 18th ed London Bailliere Tindall, 1982 206-28 3. Muller R Worms and disease a manual of medical helminthology London Heinemann, 1975 12 1
Laughlin
H2-RECEPTOR ANTAGONIST NON-RESPONDERS SIR,--Our findings (to be published in Alimentary, Plaarrnacology and Therapeutics) are not entirely in agreement with those of Dr Savarino and his colleagues (Nov 28, p 1281). We treated 32 patients with endoscopically proven duodenal ulcer with cimetidine 400 mg twice daily for 6 weeks. Overnight gastric secretion was measured before and during treatment. In 12 patients the ulcers did not heal and they had less profound inhibition of overnight acidity than those with healed ulcers p<0’01). This fits in with what Savarino et al and others have found.1.2 However, 2 patients’ ulcers failed to heal despite achlorhydria overnight on treatment. Tablet counts revealed no evidence of non-compliance. 9 of these 12 non-healers consented to further secretion studies while on cimetidine 400 mg with pirenzepme 50 mg and on cimetidine 1600 mg. Both treatments were significantly better at ,