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Biomedical subjects

G Fluge

Publications and source records attributed to G Fluge.

At least 37 records · Page 2Linked to original sources

[Recurrent abdominal pain. A prospective study of 68 children].

We followed 68 children with recurrent abdominal pain in a prospective study including a standard investigation programme and abdominal ultrasound. We found an organic disease which explained the pain in eight patients (12%). Most children with recurrent abdominal pain can be dealt with by a general practitioner. In our opinion, further investigation, including abdominal ultrasound should only be carried out in the event of specific suspicion of organic disease. At follow-up 16-34 months later, 55 children (85%) had improved or were free of pain. We discuss the differential diagnoses and propose a plan of investigation for these children.

Abdominal Pain↗

Frequency of the delta F508 and exon 11 mutations in Norwegian cystic fibrosis patients.

We have searched for the delta F508 mutation in 77 Norwegian cystic fibrosis patients. Of the 154 chromosomes tested, 93 (60%) carried the delta F508 mutation. Haplotypes at the D7S23 locus (KM19 and XV2C markers) were determined. Of 81 chromosomes with the F508 mutation, the B haplotype was found on 77. We found three patients with the G551D and one patient with the R553X mutation in exon 11 of the CFTR locus.

Cystic Fibrosis↗

Routine measurements of gluten antibodies in children of short stature.

Serum IgA and IgG gluten antibody levels were measured prospectively in 168 children without abdominal symptoms referred to the outpatient clinic for short stature. Elevated (greater than 0.30 units) gluten IgA antibody levels (0.82 +/- 0.22 units) were detected in five children (aged 8.5 +/- 1.6 years, height standard deviation score -2.14 +/- 0.26). They had probable celiac disease based on villus atrophy at duodenal biopsy, in vitro toxicity of wheat gluten, and disappearance of serum gluten antibodies after gluten withdrawal from the diet. Three of these children had elevated IgG antibody levels (greater than 0.25 units). Elevated IgG antibody levels with normal IgA levels were demonstrated in 11 short children who had normal duodenal biopsy results. It is concluded that measurement of gluten antibodies, especially of the IgA type, should be included in the diagnostic evaluation of children with short stature.

Adolescent↗

[Survey of growth retardation in children].

Following investigation of 172 children submitted for retarded growth, 34 children obtained a specific diagnosis. 11 of these children had growth hormone deficiency and five had coeliac disease. The remaining 138 children either had genetically determined short stature or their growth and adolescence was constitutionally delayed. 27 prepubertal children received treatment with anabolic steroids, and 17 children were treated with growth hormone. We present a practical approach for the investigation of retarded growth.

Adolescent↗

Influence of cow's milk proteins and gluten on human duodenal mucosa in organ culture.

Forty-five duodenal biopsies from 33 children and 3 adult patients were maintained in organ culture for 24 h and exposed to various cow's milk proteins and gluten. In 10 of 11 celiac patients with a flat duodenal mucosa, and in 2 of 4 patients with partial villous atrophy, a significant reduction in the mean enterocyte height was found after in vitro gluten exposure, compared to culture in basic culture medium. Three patients had coexisting celiac disease and cow's milk protein intolerance. alpha-Lactalbumin and beta-lactoglobulin exhibited toxic effects on flat biopsies from two of these patients, and casein was toxic in one. In 10 patients with cow's milk protein intolerance, a significant reduction in enterocyte height was noted in one case with gluten, and in three patients with casein and lactoglobulin, whereas lactalbumin did not affect the tissues. In seven control patients having a normal duodenal mucosa, no in vitro influences were noted, whereas in four patients with partial villous atrophy, a toxic reaction to gluten was seen in one and a reduced enterocyte height was seen after lactoglobulin exposure in another. In vitro toxicity induced by gluten corresponded well with the diagnosis of celiac disease, whereas toxic reactions to cow's milk proteins during organ culture were inconsistent in cow's milk intolerance, except for cases in which a marked enteropathy was documented.

Adolescent↗

Chronic inflammatory bowel disease in children in western Norway.

The incidence of Crohn's disease (CD) and ulcerative colitis (UC) in children in western Norway was estimated in a prospective epidemiological study during the years 1984 and 1985. The total population in the area was 807,000 and the child population was 198,570 (1984). There were 27 new cases of chronic inflammatory bowel disease (IBD) in children aged 15 years or less, 10 new cases of CD, and 17 of UC. The mean annual incidence of CD in the child population was 2.5/100,000/year, whereas the incidence of UC in the child population was 4.3/100,000/year. Nearly all the children had abdominal symptoms. In this study, we found an incidence of CD in children that is the highest hitherto reported, to our knowledge. To the contrary, the incidence of UC was considerably lower than previously reported from northern Europe.

Adolescent↗

Epidemiology of Crohn's disease in western Norway. Study group of Inflammatory Bowel Disease in Western Norway.

The incidence of Crohn's disease in western Norway was estimated in a prospective epidemiologic study during the years 1984 and 1985. The total population in the area was 807,000. Both inpatients and outpatients were included. Five hundred and fifty general practitioners and 12 hospitals participated in the study. A total of 86 patients were diagnosed, giving a mean annual incidence of 5.3 per 100,000. For patients between 15 and 19 years of age-specific incidence rate was 16.0 The M/F sex ratio was 0.9. In the same period 240 patients with ulcerative colitis were diagnosed (mean annual incidence, 14.8 per 100,000), giving a ratio of 2.8 between ulcerative colitis and Crohn's disease and an annual incidence of 20.1 per 100,000 for inflammatory bowel disease. Familial occurrence of IBD was found for 12% of the patients.

Adolescent↗

Epidemiology of ulcerative colitis in western Norway.

The incidence of ulcerative colitis (UC) in the three counties that compose Western Norway was registered in a prospective study during the years 1984 and 1985. Both inpatients and outpatients were included. Five hundred and fifty general practitioners and 12 hospitals participated in the study. A total of 239 patients were diagnosed in this area with 807,000 inhabitants, giving a mean annual incidence of 14.8 per 100,000. For patients between 30 and 35 years of age the age-specific incidence rate was 31.2. The M/F sex ratio was 1.10. Familial occurrence of inflammatory bowel disease was found in 11% of the patients. Patients with rectal involvement only constituted 35% of the patients.

Adolescent↗

Ceftazidime treatment of chronic Pseudomonas infection in patients with cystic fibrosis.

Twenty-one patients with cystic fibrosis (CF), aged 1-18 years, with chronic lower respiratory tract infection caused by Pseudomonas aeruginosa, received 38 treatment courses of ceftazidime of 10-14 days duration. A favorable clinical response was observed in 28 of the 38 treatment courses. The minimal inhibitory concentration values of ceftazidime for the Pseudomonas isolates were concentrated around 0.5-1.0 mg/l, although a wide range of sensitivities was found (less than 0.03-32 mg/l). P. aeruginosa was eliminated after five treatment courses, but recurred after 1 month in four of these patients. The organism was permanently eradicated in one patient until his death 8 months later. Ceftazidime was well tolerated. The doses used in this study (50 mg/kg body weight i.v. twice daily) should probably be increased in order to achieve better microbiological response.

Adolescent↗

Clinical effect and pharmacokinetics of trimethoprim-sulphadiazine in children with urinary tract infections.

The clinical effect and pharmacokinetics of the combination trimethoprim (TMP)-sulphadiazine (SD) were studied in 18 children with acute urinary tract infections (UTI), aged 2-56 months. A suspension of TMP-SD (9 + 41 mg/ml) was taken orally twice daily for 10 days. Various doses of TMP (2.9-3.7 mg/kg/day) and SD (12.9-16.7 mg/kg/day) were also given to children of different ages. After 2-4 days of treatment, bacterial cultures of urine were negative and C-reactive protein in serum, WBC count and ESR in all patients had become normal. Steady state serum levels for both components were reached after 4 or more days of treatment. At steady state, mean peak serum concentrations of TMP and SD of 1.4 micrograms/ml and 27 micrograms/ml, respectively, were found within 2-4 h after a fasting morning dose. The biological half-lives of TMP and SD were of the same order of magnitude, but the total clearance of TMP was 5 times greater than that of SD. The concentrations of TMP-SD in urine were invariably more than 10 times the minimum inhibitory concentrations (MIC) for the causative organisms (tested at the ratios 1:20 and 1:4 of TMP and SD). Non-metabolized SD constituted 77% of total SD in urine of infants, and 55% of total SD in children of 1 year or more. The TMP-SD combination showed a satisfactory clinical effect and favourable pharmacokinetic properties in children with UTI.

Anti-Infective Agents, Urinary↗

Quantification of immunoglobulins after organ culture of human duodenal mucosa.

Duodenal biopsies from 33 celiac and 16 nonceliac patients were kept in organ culture for 24 h. Quantities of immunoglobulins were measured by rocket immunoelectrophoresis in mucus removed from the biopsy surface after culture and in culture media. Increased amounts of immunoglobulins were recorded after culture of biopsies from celiac disease patients in the exacerbation state; but only in 11 of 33 celiac mucosae could an increment be detected after culture in the presence of gluten compared to culture on gluten-free medium. The amount of IgA showed a significant correlation with radioactivity of mucus and culture medium after [14C]leucine incorporation during culture. In such experiments autoradiograms of immunoprecipitates disclosed in vitro synthesis of IgA, whereas 47% of the IgG precipitates were radionegative. Amounts of IgA corresponded significantly to serum concentration of this immunoglobulin, whereas for IgM and IgG no such correlation existed. Quantification of immunoglobulins seems to be unsuitable as a method of evaluating in vitro gluten toxicity in celiac disease.

Adolescent↗

Autoradiographic localization of a gluten peptide during organ culture of human duodenal mucosa.

An 125I-labeled subfraction of Frazer's fraction III (molecular weight, 8,000) was added to the culture medium during organ culture of duodenal biopsies from two patients with celiac disease in exacerbation. The isotope-labeled gluten peptide was localized by autoradiography after 6, 12, and 24 h of culture. At 6 h, labeling was located mainly in the basal layers of the biopsies. The tissue was well preserved. After 12 h in culture, the labeling had spread to the lamina propria and the crypts. A few grains were located over enterocytes and desquamated cells. Moderate histological signs of toxicity were observed. After 24 h, there was marked toxic deterioration, comparable to that seen after culture with alpha-gliadin. Labeling had spread throughout the entire section. There seemed to be no specificity of the binding, for the entire section was affected. Culture with the identical gluten fraction, in the radionegative state, produced histological deterioration comparable to that seen after exposure to the isotope-labeled peptide. Gluten peptides are presented to the target cells in a unique way during organ culture, different from in vivo conditions. This may influence the results when the organ culture method is used to investigate the pathogenesis of celiac disease.

Adolescent↗

Brush border and lysosomal marker enzyme profiles in duodenal mucosa from coeliac patients before and after organ culture.

Five brush border and 2 lysosomal enzymes were measured in duodenal tissue explants from 21 children and young adults (16 coeliac and 5 non-coeliac) before and after organ culture. Reduced activity of brush border enzymes and increased activity of lysosomal enzymes were recorded in flat mucosas from coeliac patients compared with remission coeliac explants and biopsy specimens from non-coeliac controls. Slightly increased activity of alkaline phosphate and sucrase was recorded during culture (24 h) of coeliac explants. Coeliac specimens in the exacerbation state showed increased activity of acid phosphatase after culture in the presence of gluten, whereas gluten did not provoke detectable alterations in brush border enzyme activities during culture unless the wet weight of material was 1.5 mg or more. In such explants lower activity of brush border enzymes was measured after in vitro gluten exposure than after culture on gluten-free medium. Mucus removed from the specimen surface after culture contained considerable amounts of brush border enzymes and reflected the variations in the tissue homogenates. Culture media contained smaller quantities of enzymes.

Acetylglucosaminidase↗

DNA synthesis in human duodenal biopsies maintained in organ culture.

Incorporation of 3H-thymidine during organ culture was studied in duodenal biopsies from 14 patients. Pulse-label at various intervals disclosed active incorporations during the first 2 h in culture. Labelling index declined to low levels at 3-4 h. Thereafter incorporation increased again and persisted throughout the rest of the culture period of 11 h. The DNA synthesis rate of crypt cells between 4 and 11 h in culture was calculated in 5 patients after pulse-label and continuous labelling of explants in parallel culture. The rate of entry into DNA synthesis was about 24 cells per 1,000 crypt cells per hour in flat, coeliac biopsies, versus 9-13 in controls, Gluten did not influence DNA synthesis rate, whereas wheat germ lectin inhibited DNA synthesis. Counting of the total number of mitoses and labelled fraction of mitoses disclosed active crypt cell renewal in flat, coeliac biopsies. In normal-appearing biopsies no mitoses were labelled, indicating delayed exit from S-phase or long duration of G2-phase in these explants.

Atrophy↗

Mitotic rate and mitotic time in coeliac and non-coeliac duodenal biopsies maintained in organ culture.

Duodenal biopsies from 9 coeliac and 7 non-coeliac control patients were maintained in organ culture. In one series of experiments Colcemid sufficient to arrest cells in metaphase was added to the culture medium at various time intervals. Colcemid exposure lasted between 1 and 11 h. Mitoses did not appear until after 8 h in culture, and from that time increasing numbers of mitoses were counted up to 13 h. In a second series biopsy specimens were cultured in parallel for 11 h with and without Colcemid, and in the presence or absence of a gluten fraction. The mitotic index after 11 h in culture was 17-28 per 1,000 crypt cells in mucosae from coeliac patients, compared with 4-6 in controls (P less than 0.01). The mitotic rate was between 15 and 58 mitoses per 1,000 crypt cells per h in mucosae from coeliac patients, which was significantly higher than in controls (mitotic rate 3-23). The mean calculated mitosis time was 1.06 h. Gluten had no detectable influence on these parameters, although histological deterioration occurred after in vitro gluten exposure. Wheat germ lectin inhibited mitotic activity.

Adolescent↗