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Biomedical subjects

D H Shmerling

Publications and source records attributed to D H Shmerling.

At least 19 recordsLinked to original sources
PubMed2000

Improved general health status in an unselected infant population following an allergen-reduced dietary intervention programme: the ZUFF-STUDY-PROGRAMME. Part II: infant growth and health status to age 6 months. ZUg-FrauenFeld.

AIM OF THE STUDY: An allergen-reduced dietary intervention programme with strict dietary requirements was implemented over the first four months of life in an unselected population-based infant cohort and compared to a non-intervention cohort (the ZUFF study). Recommendations for the dietary programme in the intervention cohort were extended, but not strictly implemented, until the end of month six. The intervention was based on breastfeeding, a moderate whey hydrolysate formula (pHF), and delayed introduction of weaning foods with a high allergenicity. This study was a prospective, controlled, and unblinded study, the first to assess the effects of an allergen-reduced, pHF-based early nutritional programme in a broad unselected infant population. Because overall healthy development of the infant is a major objective of any nutritional programme, the study evaluated the effects of the dietary intervention on infant growth and general health status rather than specific allergic manifestations. Part I of this paper gave results for nutritional behaviour only, and Part II gives results for growth and general health status during the intervention period through the sixth month of life. METHODS: Assignment of study infants was to demographically comparable intervention (Z) or control (FF) cohorts according to place of birth. In the intervention cohort (Z=564), the recommended dietary regimen was breastfeeding and--if exclusive breastfeeding was not possible--supplementation with a moderately hydrolysed, allergen-reduced infant formula (pHF). Weaning foods were delayed until four months of age or later in case of weaning foods with high allergenicity. In the control cohort (FF=566), there was no specific intervention. Imbalances between cohorts in confounding (adjuvant) factors that could influence health-related outcomes were integrated as covariates into the logistic regression of the main analyses. Growth parameters included weight, length, head circumference, BMI, and Z scores (SDS). General health status was assessed by clinically significant findings in gastrointestinal, respiratory, or skin symptoms. RESULTS: Growth at 6 weeks and at 3 and 6 months was similar for Z and FF. Significantly fewer Z than FF infants had clinically noteworthy health findings at 3 months (Z=27% versus FF=37%, odds ratio=0.63, CI=0.48-0.82) and 6 months (Z=33% versus FF=49%, odds ratio=0.51, CI= 0.40-0.66). This corresponds to a 30 % reduction in overall health concerns at 6 months for the intervention cohort. At 3 and 6 months, differences between cohorts in most measures of general health status were strongly influenced by a lower incidence of skin symptoms in the Z cohort. Within FF, there were fewer exclusively breastfed (eBF) infants with health problems at 3 months compared with those who were partially (pBF) or non-breastfed (nBF) (eBF=31%, pBF=40%, nBF=39%, p< 0.05). In contrast, in the Z intervention cohort, the number of infants with health concerns was similar for exclusively breastfed infants and for those in whom mother's milk was supplemented or replaced by pHF (eBF=29%, pBF=25%, nBF=26%, ns). In a subanalysis of overall health findings in infants without a family risk of allergies, there were again significantly fewer Z than FF infants with any health or any skin problem. CONCLUSION: An allergen-reduced dietary recommendation that includes a moderate whey hydrolysate infant formula (pHF) has no negative effects on growth parameters up to 6 months of life in an infant population unselected for atopic risk. The dietary intervention produced improvements in general health status when compared with a control cohort that received infant formula with unhydrolysed proteins (IF), and high allergenic weaning foods at an earlier age. The difference between cohorts was principally due to fewer adverse skin findings. (ABSTRACT TRUNCATED)

Animals↗
PubMed2000

Improved general health status in an unselected infant population following an allergen reduced dietary intervention programme. The ZUFF-study-programme. Part I: Study design and 6-month nutritional behaviour.

BACKGROUND: The best nutritional option for newborn infants is mother's milk. However, some newborn babies may not be exclusively breastfed during the first months of life, potentially leading to reduced overall health status and the early onset of allergic diseases in some infants. Considerable research has been devoted to the development and assessment of infant nutrition programmes, particularly to the prevention of allergies in high-risk infants. However, equal numbers of infants with and without an elevated familial risk of allergies will eventually develop allergic diseases. Therefore, optimizing nutritional programmes for the early infant population as a whole is an important--but as yet insufficiently studied--area of investigation. Moreover, although safe and effective nutrition must primarily support healthy development of the infant, few studies have evaluated the overall health benefits of nutritional interventions, but have focussed on specific allergic manifestations. In animal models, an allergen-reduced moderate whey hydrolysate formula (pHF, Nestlé Beba HA) induces the development of oral tolerance towards cow's milk proteins, without inducing sensitization. In infants with a high risk for allergies, pHF formulae reduce the early onset of allergic disease during the first 5 years of life by approximately 50% compared with a dietary regimen of unaltered proteins. At present, very little is known about the overall health benefits of such a dietary intervention on the unselected infant population as a whole. AIM OF THE STUDY: The aim of our prospective, controlled study was to investigate the overall health benefits of an allergen-reduced nutritional programme in a newborn infant population unselected for atopic risk factors. The population in our study was as comparable as possible to the general population of healthy newborn infants. Our study included exclusive breastfeeding, use of a moderate whey hydrolysate formula (pHF, Nestlé Beba HA) if infant formula was needed, and delayed introduction of low-allergenic weaning foods. The study included assessments of compliance with the dietary programme, and evaluated nutritional habits, growth, and overall health status for 24 months. The health evaluation included allergic manifestations but did--by porpose--not define or evaluate them specifically. Part I of this paper gives results for nutritional habits during the first 6 months of life, Part II gives results for growth and general health status for the same time period, Part III will present feeding habits during the second half of the first year of life, and Part IV will present results to 24 months of age. The complete study report is published as a supplement to this journal. METHODS: Nutritional assignment was to demographically comparable intervention (Z) or control (FF) cohorts according to the infant's place of birth. In the intervention cohort (Z, n = 564), the recommended dietary regimen was breastfeeding and/or the pHF formula, with no weaning food before 4 months of age. In the control cohort (FF, n = 566), there was no intervention. Longitudinal diet groups, defined for 4 months, excluding dropouts and noncompliants, were exclusive breastfeeding (eBF, Z, n = 201, FF, n = 162), partial breastfeeding (pBF, Z, n = 222, FF, n = 311), or non-breastfeeding (nBF, Z, n = 43, FF, n = 62). Imbalances between groups and cohorts in confounding factors that could influence health-related symptoms were integrated as covariates into the main analyses using logistic regression. Nutritional surveillance was carried out using continuous prospective monitoring. RESULTS: The overall rate of breastfeeding, irrespective of partial or exclusive breastfeeding or the additional use of weaning foods, was similar in both cohorts at 4 and 6 months. However, from ages 3 to 6 months, significantly more Z than FF infants were exclusively breastfed (p < 0.05), and weaning foods were introduced at a significantly later age in Z t

Animals↗
PubMed1998

Effects of pancreatic enzyme preparations on erythrocyte glutathione peroxidase activities and plasma selenium concentrations in cystic fibrosis.

To substitute for exocrine pancreatic insufficiency, patients with cystic fibrosis (CF) take pancreatic enzymes (PE) originating from porcine pancreas. Five different pancreatic enzyme preparations used by our patients contained 0.5-1.4 microg selenium per g tablet. In patients taking PE in doses that were gradually increased to improve fat absorption during a 48-month period, the effects of PE dose on erythrocyte selenium-dependent glutathione peroxidase (SeGSH-Px) activities and plasma selenium concentrations were studied. At baseline, erythrocyte SeGSH-Px activities were significantly lower in patients (p=.01), while plasma selenium concentrations did not differ between patients and healthy subjects. When PE dose and, consequently, selenium intake from PE was increased, erythrocyte SeGSH-Px activities (p < .001) and plasma selenium concentrations (p=.02) increased. Changes in SeGSH-Px activities during the initial 8 months correlated with those in selenium intake from PE (r=0.67, p < .001). Plasma selenium concentrations plateaued at 12 months and erythrocyte SeGSH-Px activities did so at 36 months, when patients had reached SeGSH-Px activities similar to those of healthy subjects. At 48 months, patients took an average lipase dose of 17400 U x kg(-1) x d(-1) and selenium dose from PE of 0.53 microg x kg(-1) x d(-1). We conclude that selenium content of PE preparations has a significant effect on SeGSH-Px activity in patients with CF. This form of selenium supply needs to be taken into account when selenium supplements are given to patients with CF.

Administration, Oral↗
PubMed1998

Faecal immunoreactive lipase: a simple diagnostic test for cystic fibrosis.

UNLABELLED: The study evaluates faecal immunoreactive lipase (IRL) measurement in spot stool samples as an index of exocrine pancreatic function in patients with cystic fibrosis (CF). Stool samples (211) from 183 healthy volunteers (age range: 2 days-14.2 years) showed a normal log distribution of IRL values with a median concentration of 71.4 micrograms/g (range: 0.53-4160 micrograms/g). In 156 stool samples from 58 patients with proven CF, the median IRL concentration of 0.4 microgram/g (range: 0.003-107 micrograms/g) was significantly lower (P < 0.001) than that of normal controls. In healthy controls, IRL levels were age related with significantly higher levels (P < 0.001) shortly after birth compared to older children. Stimulation of the exocrine pancreas by oral milk feeding resulted in a significant (P < 0.001) increase in a faecal IRL concentration. Faecal IRL concentrations in meconium were very low and of the same magnitude as in patients with CF. CONCLUSION: Faecal IRL determination had a high diagnostic sensitivity (87%) and excellent diagnostic specificity (97%) in patients with CF. A negative test result (PVneg. 99%) virtually excluded CF under screening conditions.

Adolescent↗
PubMed1997

Plasma vitamin C concentrations in patients with cystic fibrosis: evidence of associations with lung inflammation.

Vitamin C status and possible associations with the disease process in cystic fibrosis (CF) patients were investigated. Plasma vitamin C concentrations in patients from two different mid-European populations (Swiss, n = 62; Austrian, n = 60) taking no or low-dose vitamin C from multivitamin supplements did not differ from each other or from control subjects (n = 34). Vitamin C concentrations decreased with age (5.05 mumol.L-1, y-1). When followed up for 12 mo, patients had the highest plasma vitamin C concentrations in February and the lowest in May and August (P < 0.01); the decrease in vitamin C was accompanied by increases in plasma malondialdehyde (P < 0.001) and tumor necrosis factor alpha concentrations (P < 0.01). During supplementation with vitamin E for 2 mo or beta-carotene for 12 mo vitamin C concentrations did not change. They correlated inversely with white blood cell count (r = -0.36, P = 0.008), bands (r = -0.36, P = 0.02), alpha 1-acid glycoprotein (r = -0.45, P = 0.002), interleukin 6 (r = -0.46, P = 0.0006), and neutrophil elastase/alpha 1-proteinase inhibitor complexes (r = -0.34, P = 0.02). In patients with vitamin C concentrations < 40 mumol/L, all indexes of inflammation were relatively high, whereas those with concentrations > 80 mumol/L (upper quartile of control subjects) showed clearly lower values. These results are consistent with the hypothesis that by scavenging oxygen free radicals vitamin C interacts with an inflammation-amplifying cycle of activation of alveolar macrophages and neutrophils, release of proinflammatory cytokines and oxygen free radicals, and inactivation of antiproteases.

Adolescent↗
PubMed1997

Reference values for plasma concentrations of vitamin E and A and carotenoids in a Swiss population from infancy to adulthood, adjusted for seasonal influences.

In a cross-sectional survey, plasma concentrations of alpha- and gamma-tocopherol, alpha- and beta-carotene (cis and trans isomers), lycopene, and retinol were determined by reversed-phase HPLC, and ratios of plasma alpha-tocopherol to cholesterol were calculated in 208 Swiss individuals ages 0.4-38.7 years. The influence of age, sex, and season of sampling was studied. Age was a significant predictor of all plasma concentrations except alpha-carotene. No sex-related differences were observed. Season of sampling affected alpha-tocopherol and retinol (higher in winter) and gamma-tocopherol and cholesterol concentrations (higher in winter and spring than in the other seasons). After correction for seasonal influences, age differences were 0.24 micromol/L per year for alpha-tocopherol, 0.04 micromol/L per year for retinol, and 0.04 micromol/L per year for cholesterol concentrations; ratios of plasma alpha-tocopherol to cholesterol were not affected by age. We constructed age-specific reference intervals from the regression line and a multiple of the standard deviation. Separate regression equations are presented for seasons with low and high values.

Adolescent↗
PubMed1996

Response to a single oral dose of all-rac-alpha-tocopheryl acetate in patients with cystic fibrosis and in healthy individuals.

Biochemical vitamin E deficiency and low plasma lipids are frequent findings in patients with cystic fibrosis (CF). The response to a single oral dose of all-rac-alpha-tocopheryl acetate [100 IU (100 mg)/kg body wt] was studied over 24 h in 25 CF patients with exocrine pancreatic insufficiency and in 23 healthy individuals. Patients received pancreatic enzymes together with the vitamin E test dose. At baseline, plasma alpha-tocopherol concentrations correlated with cholesterol concentrations; both were lower in patients than in control subjects, as were erythrocyte alpha-tocopherol concentrations (all P < 0.0001). Plasma and erythrocyte alpha-tocopherol concentrations were significantly higher than baseline concentrations from 3 and 6 h onward, respectively, and peaked most frequently at 6 and 12 h, respectively, in both patients and control subjects. Maximum increases and areas under the concentration time curves for plasma alpha-tocopherol concentrations were smaller in patients than in control subjects (P < 0.0001). When ratios of plasma alpha-tocopherol to cholesterol (to correct for differences in cholesterol concentrations) or erythrocyte alpha-tocopherol concentrations were applied, patients were shown to respond as efficiently as control subjects. On the basis of these results, we recommend vitamin E supplements in doses high enough to achieve vitamin E status in CF patients well within the range of healthy individuals; these supplements should be given with appropriate amounts of pancreatic enzymes. However, for long-term supplementation much lower doses than those used in this test situation may be sufficient.

Absorption↗
PubMed1996

Long-term oral vitamin E supplementation in cystic fibrosis patients: RRR-alpha-tocopherol compared with all-rac-alpha-tocopheryl acetate preparations.

To investigate the efficacy of three different vitamin E preparations for optimizing vitamin E status in cystic fibrosis (CF patients long-term, 29 patients (aged 0.7-29.8 y) were randomly assigned to receive 400 IU of either RRR-alpha-tocopherol (A: 268 mg, n = 10) or all rac-alpha-tocopheryl acetate as a fat-soluble (B: 400 mg, n = 10) or water-miscible preparation (C: 400 mg, n = 9) and were followed for 6 wk. In the whole study group, plasma alpha-tocopherol concentrations increased from baseline (10.5 +/- 4.6 micromol/L) to 3 wk (25.7 +/- 6.5 micromol/L; P < 0.001), but not further between 3 and 6 wk; concentrations at 3 and 6 wk did not differ from those of age-matched control subjects (23.6 +/- 3.9 micromol/L). There was no significant difference in the increase from baseline to 6 wk among preparations A (17.75 +/- 8.43 micromol/L), B (14.0 +/- 9.4 micromol/L), and C (15.5 +/- 7.1 micromol/L). Because of differences in body weight, the dose administered ranged from 5.5 to 47.4 IU x kg-1 x d-1; it correlated positively with the increase in plasma alpha-tocopherol concentrations (P < 0.001). There was no significant difference in the increase in plasma alpha-tocopherol concentrations between patients with CF-associated liver disease (n = 8) who received 10.2 +/- 3.8 IU x kg-1 x d-1 and those without liver disease taking comparable doses. We conclude that CF patients can be efficiently supplemented with 400 IU/d of any one of the three vitamin E preparations and plasma values of healthy control subjects can be achieved.

Administration, Oral↗
PubMed1996

Neutrophil elastase/alpha 1-proteinase inhibitor complex levels decrease in plasma of cystic fibrosis patients during long-term oral beta-carotene supplementation.

Lung inflammation in cystic fibrosis (CF) is associated with an increased release from activated neutrophils of oxidants and proteinases. Free radical generation is not efficiently neutralized, and the major anti-proteinase, alpha 1-proteinase inhibitor (alpha 1-PI) is thought to be oxidatively inactivated. We hypothesized that enhanced antioxidant protection could represent an additional long-term strategy to attentuate the host inflammatory response. The effect on plasma neutrophil elastase/alpha 1-PI (NE/alpha 1-PI) complex levels (as a marker of lung inflammation) and plasma malondialdehyde concentrations (as a marker of lipid peroxidation) of additional oral beta-carotene supplementation was studied in 33 CF patients who had already received long-term vitamin E supplementation. In the presence of a more than 10-fold increase in plasma beta-carotene concentrations (mean +/- SEM) (0.09 +/- 0.01 to 1.07 +/- 0.19 mumol/L; p < 0.0001), a small increase in plasma alpha-tocopherol concentrations (23.8 +/- 1.31 to 28.4 +/- 1.81 mumol/L; p = 0.02), and a more than 50% decrease in plasma malondialdehyde concentrations (1.00 +/- 0.07 to 0.46 +/- 0.03 mumol/L; p < 0.0001), plasma NE/alpha 1-PI complex levels decreased from 102.2 +/- 16.0 to 83.0 +/- 10.4 micrograms/L; (p = 0.02). Plasma retinol concentrations increased (1.05 +/- 0.06 to 1.23 +/- 0.07 mumol/L; p = 0.0001) due to conversion of beta-carotene to retinol, which could have contributed to the decrease in NE/alpha 1-PI complex levels. Based on these results, we speculate that efficient antioxidant supplementation could attenuate lung inflammation in CF.

Administration, Oral↗
PubMed1995

Enhanced resistance to oxidation of low density lipoproteins and decreased lipid peroxide formation during beta-carotene supplementation in cystic fibrosis.

We investigated the effect of correcting beta-carotene deficiency in cystic fibrosis (CF) patients on two parameters of lipid peroxidation. The resistance to oxidation of low density lipoprotein (LDL) was measured by the lag time preceding the onset of conjugated diene formation during exposure to copper(II) ions, and lipid peroxide formation was quantitated by malondialdehyde concentrations in plasma (TBA/HPLC method). Simultaneously, alpha-tocopherol and beta-carotene concentrations were determined in LDL and in plasma. Thirty-four CF patients were investigated before and after 3 months of oral beta-carotene supplementation. Beta-carotene concentrations increased (p < 0.0001) in plasma (mean +/- SD) (0.09 +/- 0.06 vs. 1.07 +/- 0.86 mumol/l) and in LDL (0.02 +/- 0.02 vs. 0.31 +/- 0.28 mol/mol), without significant changes in alpha-tocopherol, either in plasma (24.7 +/- 5.9 vs. 25.4 +/- 7.6) or in LDL (8.47 +/- 2.95 vs. 9.05 +/- 4.13). Lag times, being shorter (p < 0.05) in patients than in controls, increased from 48.5 +/- 21.3 to 69.1 +/- 27.9 min (p < 0.001) and plasma MDA concentrations, being greater (p < 0.0001) in patients than in controls, decreased from 0.95 +/- 0.32 to 0.61 +/- 0.15 mumol/l (p < 0.0001). At 3 months, lag times and MDA concentrations did not any longer differ between patients and controls. These data suggest that excess lipid peroxidation occurring in beta-carotene deficiency can be limited and normalized during efficient beta-carotene supplementation in CF patients.

Carotenoids↗
PubMed1995

Impaired resistance to oxidation of low density lipoprotein in cystic fibrosis: improvement during vitamin E supplementation.

Antioxidants such as vitamin E protect unsaturated fatty acids of LDL against oxidation. In the ex vivo model used, LDL was exposed to Cu2+ ions, a potent prooxidant capable of initiating the oxidation of LDL. The lag time, indicating the delay of conjugated diene formation in LDL due to antioxidant protection, was measured in 54 cystic fibrosis (CF) patients with plasma alpha-tocopherol levels below (Group A, n = 30) or above (Group B, n = 24) 15.9 mumol/L (mean - 2 SD of Swiss population). Patients were reevaluated after 2 months on 400 IU/d of oral RRR-alpha-tocopherol. In group A, alpha-tocopherol concentrations in LDL increased significantly from 3.2 +/- 1.6 mol/mol LDL to 8.2 +/- 2.8 mol/mol (P < 0.001) and lag times increased from 79 +/- 33 min to 126 +/- 48 min (P < 0.001), whereas in the vitamin E sufficient group B no further increase neither in LDL alpha-tocopherol concentrations or in lag times was observed. LDL oleic acid concentrations were higher, and linoleic acid concentrations were lower in patients than in controls. After efficient vitamin E supplementation, lag times were positively related to LDL alpha-tocopherol (P < 0.01) and negatively to LDL linoleic and arachidonic acid content (P < 0.001). The maximum rate of oxidation correlated positively with linoleic and arachidonic acid concentrations, as did the maximum conjugated diene absorbance. These results indicate that LDL resistance to oxidation is impaired in vitamin E deficient CF patients but can be normalized within 2 months when alpha-tocopherol is given in sufficient amounts. Linoleic and arachidonic acid content exhibit a major influence on the LDL resistance to oxidation.

Adult↗
PubMed1995

Response to oral beta-carotene supplementation in patients with cystic fibrosis: a 16-month follow-up study.

The aim of this study was to determine the efficacy of long-term oral beta-carotene supplementation for correcting impaired beta-carotene status in cystic fibrosis patients. Thirty-five patients (2.3-30.5 years of age) with coefficients of fat absorption of 46-96% (median 88%) received beta-carotene 0.5 mg/kg daily and were followed over a 16-month treatment period. Baseline plasma beta-carotene concentrations in patients (mean +/- SD, 0.09 +/- 0.06 mumol/l) were significantly lower than those of age-matched controls (0.86 +/- 0.56 mumol/l) (p < 0.0001). Concentrations increased rapidly and reached a plateau at or before 3 weeks that was maintained throughout the study period. Values obtained at 3 weeks (0.89 +/- 0.64 mumol/l) were significantly higher (p < 0.0001) than those at baseline and did not differ from controls. Plasma retinol and alpha-tocopherol concentrations increased during the observation period, but remained within normal ranges. Plasma retinyl palmitate, which was below the detection limit in all but one patient at baseline, did not increase. Thus oral beta-carotene supplementation is effective and normalizes beta-carotene status of cystic fibrosis patients without evidence of significant side effects.

Adjuvants, Immunologic↗
PubMed1994

A paediatric Crohn's disease activity index (PCDAI). Is it useful? Study Group on Crohn's Disease in Children and Adolescents.

Since 1976, various activity indices for Crohn's disease have been developed but none has been suitable for use in the paediatric age group. Therefore, the German-Swiss Study Group on Crohn's Disease in Children and Adolescents decided to develop their own paediatric Crohn's disease activity index (PCDAI) by multiple regression analysis of prospectively collected data. The result was a simple index consisting of two clinical (appetite, number of stools/week) and four laboratory variables (erythrocyte sedimentation rate, serum iron and alpha 2-globulin concentrations and bands as percentage of white blood cells). Applying the index to patients who were followed-up, it could be demonstrated that the changes in PCDAI inversely reflected the changes in weight and that the surgical removal of the inflamed parts of the gut reduced the disease activity index to levels comparable to those obtained in patients after successful, exclusively conservative, treatment. Low disease activity was maintained for at least three years.

Adolescent↗
PubMed1992

Short-term changes in erythrocyte alpha-tocopherol content of vitamin E-deficient patients with cystic fibrosis.

Polyunsaturated fatty acids of biomembranes are a major target of lipid peroxidation. In vitamin E deficiency an efficient delivery of a high oral loading dose of all-rac-alpha-tocopheryl acetate to erythrocyte membranes could provide an early onset antioxidative effect. We investigated short-term changes in erythrocyte alpha-tocopherol after a single oral dose of 100 mg all-rac-alpha-tocopheryl acetate/kg in 10 vitamin E-deficient cystic fibrosis (CF) patients. Over 24 h, erythrocyte alpha-tocopherol increased 68% to 420% of preloading concentrations. With two exceptions, peak values were achieved 12 or 24 h after administration, which was 3-18 h later than peak plasma concentrations. Separate median-based curve estimates for the changes in erythrocyte alpha-tocopherol for five patients with and five without associated cholestatic liver disease were obtained. Cross-sectional test results revealed significantly lower erythrocyte alpha-tocopherol for the 9- and 24-h observations for patients with cholestatic liver disease compared with those without. Oral all-rac-alpha-tocopheryl acetate can be rapidly incorporated into erythrocyte membranes in vitamin E-deficient CF patients.

Adolescent↗
PubMed1992

Progressive idiopathic cholestasis presenting with profuse watery diarrhoea and recurrent infections (Byler's disease).

The second child of healthy unrelated parents presented with chronic diarrhoea since the age of two months, initially associated with non-characteristic liver involvement. Recurrent infections, severe failure to thrive and various metabolic deficiencies complicated the further course, as well as profuse watery diarrhoea with elevated regulatory gut peptides, responding only to somatostatin analog treatment. At 22 months of age, intermittent cholestasis with permanently normal serum gamma-glutamyltransferase was evident. The child died of fulminant purulent meningitis at the age of three years six months. Liver histology showed intrahepatic cholestasis, bile duct paucity with focal proliferation as well as slight portal and intralobular fibrosis. The clinical, biochemical and histopathological findings were indicative of Byler's disease.

Cholestasis, Intrahepatic↗
PubMed1990

[Diagnosis and treatment of celiac disease--what is the status in 1990?].

Summarizing the development of experiences and discussions of the last 20 years, a working group of the ESPGAN has recently updated the criteria of diagnosis of coeliac disease. The reliable finding of the initial typical mucosal lesion in the untreated patient is a hallmark of the disease and, if followed by an unequivocal clinical response to a gluten free diet, can be considered as final evidence for the diagnosis. Gluten challenges should be limited to cases without this evidence. High levels of antigliadin- and antireticulin- or or antiendomysium antibodies are supportive for the diagnosis but cannot substitute biopsy proof of the disease. The importance of a very long term strict gluten free diet in coeliac disease is established by recent evidence showing that in such cases there is no increased risk of malignancy.

Celiac Disease↗