Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine.

AIM: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. METHODS: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. RESULTS: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p < 0.001). CONCLUSION: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.

Small bowel biopsy in Swedish paediatric clinics.

AIM: A correct diagnosis of coeliac disease, one of the most common chronic diseases in Swedish children, demands small bowel biopsy, which can be performed endoscopically or by means of a peroral capsule. Recently there was a debate among Swedish paediatric gastroenterologists, with some advocating the cessation of capsule biopsy in favour of endoscopic biopsies. To gain information on which to base a recommendation for which technique to use, the Swedish Working Group for Childhood Coeliac Disease was commissioned to carry out a national questionnaire study on current small bowel biopsy routines in Swedish paediatric clinics. METHODS: A questionnaire concerning biopsy routines in the year 2000 was sent to all paediatric clinics performing biopsies. A reply was obtained from 39 of 40 clinics, covering 98% of the Swedish population. RESULTS: Some 1400 biopsies were performed, 64% of which were capsule biopsies and 36% endoscopic. Three clinics performed all biopsies endoscopically and 11 clinics all via a capsule. At endoscopy all children were under deep sedation or full anaesthesia, while most children undergoing capsule biopsy were under light or deep sedation. The oxygen saturation was monitored during endoscopy but less often or never during routine capsule biopsy. The presence of the parents during biopsy varied according to the degree of sedation: at 97% of the clinics performing capsule biopsy on children under light sedation, the parents were present during the whole procedure, whereas no parents were present at clinics where the biopsy was performed endoscopically under anaesthesia. CONCLUSION: Compared with the results of a similar questionnaire concerning biopsy routines performed in the early 1990s, children are now more effectively sedated. Furthermore, there is an obvious trend from capsule towards endoscopic biopsy. Both the endoscopic and the capsule biopsy techniques are useful and satisfactory for obtaining small bowel mucosal samples providing that the children are effectively sedated. For practical and economic reasons the capsule biopsy technique will probably continue to be used, although to a lesser extent than today.

Analysis of short stature homeobox-containing gene ( SHOX) and auxological phenotype in dyschondrosteosis and isolated Madelung deformity.

Dyschondrosteosis (DCO; also called Léri-Weill syndrome) is a skeletal dysplasia characterised by disproportionate short stature because of mesomelic shortening of the limbs. Madelung deformity is a feature of DCO that is distinctive, variable in expressivity and frequently observed. Mutations of the SHOX (short stature homeobox-containing) gene have been previously described as causative in DCO. Isolated Madelung deformity (IMD) without the clinical characteristics of DCO has also been described in sporadic and a few familial cases but the genetic defect underlying IMD is unknown. In this study, we have examined 28 probands with DCO and seven probands with IMD for mutations in the SHOX gene by using polymorphic CA-repeat analysis, fluorescence in situ hybridisation (FISH), Southern blotting, direct sequencing and fibre-FISH analyses. This was combined with auxological examination of the probands and their family members. Evaluation of the auxological data showed a wide intra- and interfamilial phenotype variability in DCO. Out of 28 DCO probands, 22 (79%) were shown to have mutations in the SHOX gene. Sixteen unrelated DCO families had SHOX gene deletions. Four novel DCO-associated mutations were found in different families. In two additional DCO families, the previously described nonsense mutation (Arg195Stop) was detected. We conclude that mutations in the SHOX gene are the major factor in the pathogenesis of DCO. In a female proband with severe IMD and her unaffected sister, we detected an intrachromosomal duplication of the SHOX gene.

Screening for adult coeliac disease - which serological marker(s) to use?

OBJECTIVE: To determine which serological marker(s) to use when screening for coeliac disease. DESIGN: In a population-based cross-sectional study we compared the use of antigliadin antibodies (AGA) of isotypes IgA and IgG, antiendomysial antibodies (AEA) of isotype IgA and antitransglutaminase antibodies (ATGA) of isotype IgA for detecting coeliac disease amongst adults. SETTING: Northern Sweden. SUBJECTS: A total of 1850 of 2500 (74%) invited adults (aged 25-74 years) who were randomly selected from the population register after stratification for age and sex. MAIN OUTCOME MEASURES: The sensitivity, specificity and predictive values of the AGA, ATGA and AEA tests. RESULTS: Nine cases of biopsy proven, previously undiagnosed coeliac disease were detected by screening. The sensitivity of both ATGA and AEA was 100% whilst AGA IgA and IgG both had a sensitivity of 89%. The AEA test had a specificity of 100% whereas the specificities of the ATGA, AGA IgA and IgG tests were 97, 96 and 78%, respectively. The positive predictive value for the AEA test was 100%, whereas it was considerably lower for the other tests (ATGA > AGA IgA > AGA IgG), with further decreases for all tests when shifting from a clinical to a screening situation. CONCLUSIONS: When screening for coeliac disease we suggest a serial testing approach, i.e. an initial ATGA test and, when positive, followed by an AEA test, provided that IgA deficiency has been excluded. However, assessment of the small intestinal mucosal morphology is still required to ascertain the diagnosis.

New automated immunoassay measuring immunoglobulin A antigliadin antibodies for prediction of celiac disease in childhood.

The prevalence of celiac disease (CD) in Sweden is about 4 cases per 1,000 people. Screening for CD with serological tests indicates similar high prevalences in many other countries. Between 1 November 1992 and 30 April 1995, 133 children (9 months to 16.7 years of age) with suspected CD were studied. The predictive value (PV) of immunoglobulin A antigliadin antibodies (IgA-AGA) in the serum as assayed with two new commercial automated immunoassays--the Pharmacia CAP System Gliadin IgA FEIA (CAP) and the UNICAP-100 (UNICAP)--and with three "in-house" methods was evaluated using assessment of the small intestinal mucosa morphology as the "gold standard." All serum samples were analyzed for total serum IgA. At presentation the diagnostic sensitivities and specificities of the different tests varied from 0.72 to 0.88 and 0.67 to 0.87, respectively. All methods showed a higher sensitivity for CD in younger children. The area under each assay's receiver operating characteristic curve was calculated and varied between 0.82 and 0.89. The positive and negative PVs for the CAP and UNICAP, which were assays with a high sensitivity and a high specificity, respectively, were estimated. In the clinically selected population (prevalence of CD, 1 in 3) the positive PV was about 55%, and in the general population (prevalence, 1 in 250) it was about 1%. The negative PVs for both CAP and UNICAP were close to 100%; thus, when the AGA test was negative, the risk for CD was small. Interestingly, five children had serum IgA levels below the detection limit (<0.07 g/liter) when on a gluten-free diet, whereas they had normal levels at the time of the first biopsy. In conclusion, the automated immunoassays--based on ImmunoCAP technology--for analysis of IgA-AGA had a reliability comparable to that of the in-house methods.

Patients with implantable cardioverter-defibrillators and their conceptions of the life situation: a qualitative analysis.

The implantable cardioverter-defibrillator (ICD) is today widely used for the treatment of sudden cardiac near-death episodes as a result of malignant ventricular dysrhythmia. After examining the literature, only four descriptive studies, all carried out in the USA, with a qualitative analysis based on ICD-patients' own perspectives on their life situation have been found. The aim of this study was to describe how patients living with an ICD-device in south-western Sweden conceive their life situation. As the focus was on patients' conceptions seen from a holistic perspective, an analysis inspired by phenomenography was employed on a strategic sample of 15 ICD-patients. Six categories emerged: a feeling of safety, a feeling of gratitude, a feeling of being, having a network, having a belief in the future, and gaining awareness. Although the findings cannot be generalized because of the descriptive research design, they illuminate the beneficial as well as intrusive effects of such a device, and emphasize the need for support groups for patients and families as well as further education for personnel in hospital and primary health care.

High prevalence of undiagnosed coeliac disease in adults: a Swedish population-based study.

OBJECTIVE: To determine the prevalence of coeliac disease in a population-based sample of Swedish adults. DESIGN: Population-based cross-sectional study. SETTING: Northern Sweden. SUBJECTS: A total of 1894 adults (76%) out of 2500 invited, randomly selected from the population register after stratification for age and sex. MAIN OUTCOME MEASURES: Prevalence of biopsy verified coeliac disease, symptoms of undiagnosed cases, and results of antiendomysium and antigliadin serum antibody tests. RESULTS: Coeliac disease was confirmed by intestinal biopsy showing enteropathy in 10 individuals (seven women and three men), corresponding to a prevalence of 5.3 per 1000 (95% CI = 2.5-9.7). The majority of cases (eight out of 10) had not been diagnosed prior to the screening, although many had symptoms compatible with coeliac disease. All individuals with antiendomysium antibody positivity who were subjected to a small intestinal biopsy had enteropathy. Furthermore, all of them also had elevated levels of antigliadin antibodies type IgA and/or IgG. CONCLUSIONS: Coeliac disease is common, albeit mostly undiagnosed, in Swedish adults. It is likely that the situation is no better in other countries. This highlights the importance of keeping coeliac disease in mind, and of promptly investigating individuals with unexplained, even mild, symptoms compatible with the disease. Serological markers, e.g. antigliadin and antiendomysium antibodies, are useful tools within this active case-finding strategy, although the final diagnosis should be based on an intestinal biopsy demonstrating enteropathy.

[Proposed criteria for diagnosis of celiac disease in children]. / Förslag till kriterier för celiakidiagnos hos barn.

At a seminar arranged in September 1997 by the Swedish Paediatric Working Group for Coeliac Disease, a diagnostic protocol proposed by the working group was approved by a majority of the paediatricians present, representing almost all paediatric units in Sweden. Briefly, a small bowel biopsy is called for in all children, both at presentation and as a control during gluten-free dieting. Subsequent gluten challenge and biopsy are mandatory only in cases of atypical presentation or if the diagnosis is questioned at some future date. Serum antigliadin and anti-endomysial antibody tests are complementary tools. Agreement was also reached regarding the institution of a national coeliac disease registry.

Small bowel biopsy in Swedish paediatric clinics.

The capsule technique for small bowel biopsy performed at Swedish paediatric clinics was evaluated using two questionnaires in 1990 and 1993, respectively. Replies were received from all 45 centres which together perform approximately 2300 biopsies per year. Clotting function tests prior to biopsy were carried out in 42% of the centres. The biopsies were performed under intubation anaesthesia in 13% of the centres. The most striking difference between the answers to the two questionnaires was the mode of sedation. The use of intravenous sedatives increased from 40% of the centres in the first questionnaire to 59% in the second one. The use of the oral, rectal and intramuscular routes decreased correspondingly. The most frequently used drugs for intravenous sedation were benzodiazepines, in the first questionnaire diazepam and in the second one midazolam. The failure rate was approximately 5%. In the first questionnaire, no complication was encountered. In the second questionnaire, three cases of intramural duodenal haematoma were reported, one of which led to pancreatitis. We conclude that by focusing on questions of sedation these rather simple questionnaires may have resulted in more effective sedation of children undergoing small bowel biopsy.

Tubal function and surgery in chronic otitis media. A study on the predictive value of testing tubal function, Valsalva's manoeuvre and volume of ear spaces.

In 141 ears with central tympanic membrane (TM) perforation preoperative tubal studies as well as volume determination of the air-filled ear spaces was performed. Tubal patency was checked with Valsalva's manoeuvre and pressure equilibration function with Toynbee's test and aspiration-deflation tests respectively. At postoperative control 74.5% of the ears had intact movable TM (healed), 5.7% had intact but immovable or retracted TM and 19.8% had perforation (defect). There was no difference between the healed and defect ears regarding results in aspiration-deflation tests. A positive Valsalva's manoeuvre was significantly more frequent in the healed ears. Ears with a small air-filled volume and negative Valsalva's manoeuvre showed significantly lower healing rate than ears with positive Valsalva's manoeuvre and a large air-filled volume.

Ostial and nasal patency in chronic maxillary sinusitis. A long-term post-treatment study.

In a long-term follow-up study (mean 3.5 years) after treatment of chronic maxillary sinusitis of either rhinogenous or dental origin, 72 sinuses in 66 patients were examined with respect to maxillo-ostial and nasal resistance. In sinusitis of rhinogenous etiology, the mean equivalent ostial diameter was pathologically narrowed (0.89 mm, in patients treated conservatively) whereas it was normal (2.51 mm) in sinusitis of dental etiology (dental treatment in combination with local sinus surgery). In the former group, all sinuses were diseased, compared with 3 out of 23 in the dental group. In order to distinguish between functional and organic ostial stenosis, the patients were also tested after physical exercise. The functional ostial diameter in healthy sinuses was significantly increased in contrast to the diseased sinuses. In one patient the narrow ostium was due to mucosal swelling only, but in the other cases was caused mainly by an organic stenosis. In sinusitis of rhinogenous etiology, a pathologically increased nasal resistance was found in 14.3%, while the corresponding figure in the dental group was 4.3%. Improved sinusal and nasal ventilation, achieved either pharmacologically or, preferably by surgical intervention, seems necessary for successful treatment of chronic maxillary sinusitis.

Studies on the maxillary ostial function in cases with maxillary pain, intrasinusal cysts and chronic sinusitis.

The maxillary ostial function, measured as pressure transmission capacity, ostial airway resistance, equivalent ostial diameter during nasal breathing and with a constant artificial air-flow of 16.7 cm3 X S-1 into the sinus, was compared in three groups of patients. One group consisted of 7 sinuses in 6 patients with maxillary pain but without any signs of sinusitis; a second group of 6 sinuses in 6 patients with intramaxillary cysts; and a third group of 6 sinuses in 5 patients with chronic maxillary sinusitis. No impairment of the ostial function was found in groups one and two. In the third group an increased airway resistance of the ostia and small equivalent ostial diameters were found in both sitting and recumbent positions. With the pressure recording technique, the ostium can be judged as patent, non-patent, or partially obstructed, but no further grading can be done. With the pressure-flow technique the ostial function can be evaluated as ostial resistance or equivalent ostial diameters under 'physiological conditions' when the ostium is patent. With a constant artificial air-flow into the sinus the equivalent ostial diameter can be estimated even in non-patent ostia but the equivalent ostial diameters obtained do not always reflect the true functional state of the ostium.

Patency tests of the maxillary ostium in health and disease.

Three different maxillary ostial function tests (simultaneous pressure recording in nose and sinus; simultaneous differential pressure and flow recording across the ostium; pressure recording at a constant artificial air-flow into the sinus) have been evaluated on healthy subjects and used in clinical materials. No quantitative evaluation of the ostial function was possible when using the simultaneous nasosinusal pressure recording method. The ostial function can be expressed as ostial resistance or as corresponding equivalent ostial diameter with the pressure-flow and the constant artificial air-flow methods. An isolated determination of the ostial function in both sinu-nasal and naso-sinusal directions during nasal breathing was only possible with the pressure-flow method. No impaired ostial function was found in cases with maxillary pain and intrasinusal cysts, but in chronic sinusitis the ostial function was considerably deteriorated. In cases with impaired ostial function the constant artificial air-flow method does not mirror the true functional state due to the non-physiological air-flow level used. Thus, the pressure-flow method seems to be the most physiological one.

Pulse volume recordings in outer ear canal in pulse synchronous tinnitus. A comparison between ears with Glomus tumour, serous otitis media, and normal ears.

With the aid of a volume flowmeter it is possible to record pulse synchromous volumetric changes in the outer ear canal. In 7 ears with glomus tumour in the tympanic cavity and in 5 with serous otitis media, such changes were larger than in 125 persons with a normal middle ear. By changing the ambient pressure in a pressure chamber and instructing the patients not to swallow, the drum can be pushed inward or outward. In all the cases of glomus tumour studied the pulse volumetric change was considerably affected when the drum was pushed inward or outward. In the normal patients the change was no change at all. This means that the pulse volume changes in normals are generated mainly by the vessels in the outer ear canal.