Long-term sequelae of Helicobacter pylori gastritis

brother/sister. Half of the parental couples feared that one of their healthy children might also develop IDDM. Nine of these couples and six other couples intermittently analysed blood glucose concentrations in a healthy child because they feared suspected symptoms; another motivation was to create solidarity with the affected child. Half the parents were alert to possible symptoms in healthy offspring. In six of 14 families (43%) with two or more healthy siblings the family had a strong feeling which child could become the next patient, which might be considered as preselection. Half of the parents (n=33) and siblings older than 12 years (n= 18) wanted to know the outcome of the prediction study. Five of ten families with children under 12 years wished to know the test results of their offspring; two couples would inform their children about the outcome. The most cited reason for learning the results was curiosity (51 %) which could be considered as a defence against fear, given the profound impact of IDDM in most families. Other reasons were to be better prepared for the onset of the disease (25%), or to prevent the disorder by a healthier life-style (14%), resolution of uncertainty (6%), or early recognition of possible symptoms (4%). Reasons mentioned by participants in the prediction study who refrained from test results (n=42) were fear of the result (48%), lack of treatment options (24%), fear of preoccupation with symptoms (19%), or unreliability of the test (9%). One couple feared guilt feelings if one of them were identified as a carrier. Although the risk for first-degree family members of developing IDDM is low (3-5%),2 manifestations of fear such as preoccupation with symptoms, preselection, and analysis of blood glucose levels are common. Little is known about the impact of predictive testing for IDDM on family life. Bennet Johnson et al showed that increased anxiety after high-risk results declined after 4 months. Identified carriers denied that they would develop IDDM in the future.3 In the medium and long term, identification of high risk for IDDM may offer the opportunity for adjustment in parents and child to a future disease, resolution of (parental) uncertainty, and early recognition of symptoms. Parents may consider taking responsibility for their children.4 However, identification may also burden the child’s personal development, lead to treatment of the child as if he or she had the disease, affect future adult autonomy, and raise problems with employment or insurance. Yet more than 90% will learn that they will not develop IDDM in the future.2 Whether a favourable test result will have untoward consequences such as absence or lack of relief for a lengthy period after the test, or "survivors’ guilt" as seen in predictive testing programmes for Huntington’s disease,’ remains to be seen. In IDDM families it has yet to be seen how families will cope with precise risk assessment. *A Wagner, A Tibben, G J Bruining, H J Aanstoot, I Tiems, M J C E Blondeau, M F Niermeijer Departments of *Clinical Genetics, Congenital/Hereditary Disease, and Health Policy & Management, and Medical Ethics Committee, Erasmus University, 3000 DR Rotterdam, Netherlands; and Sophia Children’s Hospital, Rotterdam

1 2

3

4

5

Report of a Working Party of the Clinical Genetics Society (UK). The genetic testing of children. JMed Genet 1994; 31: 785-97. Palmer JP, McCulloch DK. Prediction and prevention of IDDM. Diabetes 1991; 40: 943-47. Bennet Johnson S, Riley W, Apperson Hanson C, Nurick M. Psychological impact of islet-cell antibody screening. Diabetes Care 1990; 13: 93-97. Ryan MP, French J, Al-Mahdawi S, et al. Genetic testing for familial hypertrophic cardiomyopathy in newborn infants. BMJ 1995; 310:

Long-term sequelae gastritis

of Helicobacter pylori

SiR-Kuipers and colleagues’ (June 17, p 1525) important prospective study confirms the importance of Helicobacter pylori in the aetiology of gastric mucosa atrophy, and shows that age per se is not a risk factor, provided that carriage of H pylori is controlled for. It is noteworthy that most infected patients did not develop atrophy. Moreover Kuipers et al were unable to detect any factors at initial screening that predicted the subsequent development of atrophy: neither the titre of antibodies against H pylori nor the activity of gastritis had any predictive value. The outcome of H pylori infection probably depends on features of the bacterium, the host, and the environment. We are studying the host features that might determine the outcome of H pylori infection. Variations in the immune system are candidates. H pylori stimulates recruitment of antigen-presenting cells that use HLA (human leucocyte antigen) molecules to present bacterial antigens to Tlymphocytes. H pylori infection increases mucosal expression of HLA class II molecules. Polymorphism in HLA molecules is associated with different outcomes of other infections’ and with susceptibility to autoimmune diseases including the gastric mucosa atrophy of addisonian pernicious anaemia.2 The HLA class 2 molecules present antigens to CD4 cells which control the immune response to infectious agents.’ Hence we asked whether the host’s HLA-DR or DQ type affects progression to atrophy in H pylori infection. Consecutive caucasian patients of north-west European origin were recruited before upper endoscopy. We excluded patients with autoimmune diseases, those taking corticosteroid or immunosuppressive drugs, and those who had had H pylori eradication therapy. H pylori was diagnosed by rapid biopsy urease test, culture, and histology. Patients were deemed to be infected if two or more of these tests were positive, and uninfected if all three were negative. We identified 43 infected patients, including eight with duodenal ulcers and two with gastric ulcers. Of these, 17 had gastric mucosal atrophy with or without intestinal metaplasia (GMA/IM) (10 male, 7 female, age 28-70 years) and 26 did not have GMA/IM (15, 11, 24-70). 14 patients were not infected (7, 7, 28-70). Three biopsy samples were taken from the antrum and three from the corpus at the mid point of the greater curvature for histology. The presence of GMA/IM was assessed according to the Sydney system4 by a histopathologist blinded to the endoscopic, bacteriological, and HLA data. No patients had dysplasia. HLA-DR and DQ typing was by standard serological methods and with the PCR-ARMS techniques on genomic DNA from peripheral blood leucocytes. Frequencies were compared by chisquared test with Yates’ correction and correction for

multiple comparisons. We showed no association between GMA/IM and any of the HLA-DR types; the HLA-DQ typing revealed the pattern shown in the table of distribution of DQ frequencies among the groups. The frequency of DQ 5 differed between groups. It was significantly higher in the group with evidence of atrophy or metaplasia than in both the H pylori infected without GMA/IM (*in the table) (65% vs 19%; p<0-05; relative risk 3-1, 95% CI 1-7) and the uninfected group (tin

856-59. Tibben A,

Vegter vd Vlis M, Niermeijer MF, et al. Testing for Huntington’s disease with support for all parties. Lancet 1990; 335: 553.

Table: DQ frequency

according to

H

pylori status 381

the table) (65% vs 7%; p>p<0-05; 2-9; 1-6). These findings suggest that immunogenetic factors determines the development of atrophy in H pylori infection. A linkage between HLA-DQA genotypes and peptic ulceration in H pylori infection has been shown but there are few data on the host determinants of atrophy.5 The development of atrophy seems to be an important step towards gastric cancer and it seems that immunogenetic factors can influence the outcome following H pylori infection. Ian L P Beales, Nick J Davey, Charles D Pusey, Robert I Lechler, *John Calam Departments of *Medicine and Immunology, Royal Postgraduate

2 3

4

5

Medical School,

Hill AVS, Allsopp CEM, Kwiatowski D, et al. Common West African HLA antigens are associated with protection from severe malaria. Nature 1991; 352: 595-600. Kaye MD. Immunological aspects of gastritis and pernicious anaemia. Balliere’s Clin Gastroenterol 1987; 1: 487-506. Pullen AM, Marrack P, Keppler J. The T cell repertoire is heavily influenced by tolerance to polymorphic self antigens. Nature 1988; 335: 796-801. Price AB. The Sydney system. J Gastroenterol Hepatol 1991; 6: 207-08. Azuma T, Konishi J, Tanaka Y, et al. Contribution of HLA DQA gene to host’s response to Helicobacter pylori. Lancet 1994; 343: 542-43.

Nasal airway versus oral route for infant resuscitation SIR-Guidelines for infant cardiopulmonary resuscitation recommend that a rescuer places his or her mouth over the infant’s nose and mouth, creating a seal.’ Tonkin and colleagues (May 27, p 1353) have shown that this is not always achievable because the rescuer’s mouth is not large enough to encompass both nose and open mouth. We have examined whether the nasal or oral airway is the better route for resuscitation. Approval for the study was given by the Auckland Hospital ethics committee. Informed parental consent was obtained for 20 infants presenting for routine surgery under general anaesthesia. These infants had no cardiovascular or respiratory disease. After induction of anaesthesia, infants were given a muscle relaxant (vecuronium 01 mg/kg or atracurium 0-5 mg/kg). The lungs were hand ventilated with oxygen and halothane 0-5% with a Mapleson E breathing system (fresh gas flow 3-4 L/min, inspiratory time about 1 s, peak airway pressure 25 cm H2O). Artificial ventilation was then attempted through the nose for ten insufflations and then the mouth for ten insufflations with a Laerdal infant (size 00) mask. Head tilt-chin lift and jaw thrust manoeuvres were used to achieve airway patency. Oropharyngeal airways were not used. An independent anaesthetist observed chest expansion, end-tidal carbon dioxide in expired air (capnography), and stomach insufflation. Gastric distension was confirmed by nasogastric aspiration of air. Ventilation was considered successful if there was chest expansion with an end tidal carbon dioxide tracing. We investigated 20 infants, median age of 4 months (range 17 days to 6 months) and median weight 6-4 kg (2-8-9). All infants were successfully ventilated by the nasal route. Four infants were successfully ventilated by the oral route. Gastric distension occurred in ten infants when ventilated by mouth. The nasal route was better than the oral route in our model of an areflexic atonic infant. These data are consistent with known infant airway anatomy and physiology. The nasal airway is the normal route for air entry. The tongue is large in comparison with the oral cavity, opposes the soft palate posteriorly, and there 382

*E

J Torrie, B Anderson

Segedin,

PICU, Auckland Children’s Hospital, Auckland, New Zealand

1

2

Hammersmith Hospital, London W12 ONN, UK

1

is an epiglottic-palatal seal. Although 40% of full-term infants demonstrate the ability to switch from nasal to oral breathing,’ the nasal route is preferred. Our data support mouth-to-nose ventilation in preference to mouth-to-mouth ventilation for resuscitation of apnoeic infants.

3

Guidelines for cardiopulmonary resuscitation and emergency cardiac care: part V: Pediatric basic life support. JAMA 1992; 268: 2254. Sasaki CT, Isaacson G. Functional anatomy of the larynx. Otolaryngol CI N Am 1988; 21: 595-611. Miller MJ, Martin RJ, Carlo WA, et al. Oral breathing in newborn infants. J Pediatr 1985; 107: 465-69.

Management

of

leucopenic sepsis

SiR-Controlled trials of antiendotoxin and anticytokine therapy in sepsis have given disappointing results.’ We report a case that illustrates the difficulties of assessing these treatments.

A

with familial adenomatous polyposis admitted for proctomucosectomy and loop ileostomy. Before operation he received co-amoxiclav as prophylaxis. 3 days he clinical postoperatively developed signs of diffuse with fever to 40-4°C, peritonitis tachypnoea, tachycardia, up hyperbilirubinaemia (51-3 )Jbmol/L), and thrombocytopenia (18X 109/L); postoperative leucocytosis was followed by sudden leucopenia (37X1O9/L). Thus all the criteria for sepsis2 were positive. A second laparotomy revealed fibrinopurulent peritonitis with 1 L pus which proved to contain Escherichia coli, Klebsiella oxytoca, and haemolytic streptococcus type B. No leakage was detected from the gut or pouch. Management was by cleaning and lavage with physiological saline. The patient was started on a 12-day course of cefmenoxime 2 g, amikacin 0-4 g, and metronidazole 0-5 g every 8 h. 5 h after the operation all the sepsis criteria remained positive apart from fever (37-9°C), and the white cell count had declined to 1-3X10"/L. At this point granulocyte colony-stimulating factor (rhu-G-CSF, Amgen, Thousand Oaks, California) was given in a dose of 300 jig subcutaneously, as an emergency indication based on results in animals.3 2 days later a third laparotomy with lavage indicated a great reduction in inflammation. The patient was eventually discharged in good health. Before most indices of G-CSF administration inflammation were greatly increased-C-reactive protein, elastase, interleukin-6, soluble tumour necrosis factor (TNF) receptors I and II-whereas TNF and interleukin-1 were almost undetectable. After G-CSF administration, several indices changed sharply (figure): in particular, the leucocyte count increased threefold within 2 h and interleukin-6 concentrations fell by 80% within 10 h. Were these improvements due to treatment with G-CSF? Probably so; but interpretation is confounded by other treatments including antibiotics and surgery. There are three new strategies in sepsis trials. The first is select those groups of patients who are most likely to respond. In this case the fact that the genetic lesion for Gardner’s syndrome is located on the part of chromosome 5 that also accommodates most of the haemopoietic growth factors (though not G-CSF) may be relevant.4 The second is

36-year-old man (Gardner’s syndrome) with ileoanal J-pouch

to

use

was

laboratory indices, including cytokine levels,

as

surrogates for mortality, at least in pilot studies and phase 1/11 trials; our case illustrates the wide range of candidates for measurement, singly or in combination. Finally, those who are to conduct multicentre studies should ensure that