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Biomedical subjects

O Hernell

Publications and source records attributed to O Hernell.

At least 19 recordsLinked to original sources

Total energy expenditure and physical activity level in healthy young Swedish children 9 or 14 months of age.

OBJECTIVES: To measure total energy expenditure (TEE) and total body water (TBW) in healthy Swedish children 9 or 14 months of age. To compare their TEE with current recommendations for energy intake. To define their body composition and relate this to energy expenditure. DESIGN: : Children were investigated at 9 or 14 months. The following variables were measured: TEE and TBW (by the doubly labelled water method), weight and length. Total body fat (TBF), sleeping metabolic rate, activity energy expenditure and physical activity level (PAL) were calculated. SUBJECTS: Thirty infants 9 months of age and 29 children 14 months of age. RESULTS: : TEE was 323+/-38, 322+/-29, 313+/-23 and 331+/-28 kJ/kg/day in 9-month-old girls, 9-month-old boys, 14-month-old girls and 14-month-old boys, respectively. At 9 months of age girls and boys contained 29.6+/-4.8 and 29.7+/-4.5% TBF, respectively. At 14 months the corresponding figures were 29.1+/-4.3 and 28.2+/-4.3%. There was a significant negative relationship between PAL and %TBF (r=-0.81, P<0.001, n=59). CONCLUSIONS: Measured TEE plus calculated energy cost of growth confirm previous estimates that the physiological energy requirements of children 9 and 14 months of age are 15-20% lower than current recommendations for energy intake. One possible interpretation of the relationship between PAL and %TBF is that children with a high TBF content are less physically active than children with less TBF. However, this relationship needs further studies.

Anthropometry↗

Children born in the summer have increased risk for coeliac disease.

STUDY OBJECTIVE: Coeliac disease, also called permanent gluten sensitive enteropathy, is being recognised as a widespread health problem. Defining the possible role of environmental factors in its aetiology might open doors to primary prevention. This study therefore analysed if the risk for coeliac disease varies with month of birth as a proxy for a seasonal pattern for possible causal environmental exposure(s). DESIGN: A population based incidence register of coeliac disease in children below 15 years of age covering the period from 1973 to 1997. Incidence rates were calculated by month of birth, stratified for age at diagnosis. Poisson regression analyses were used to estimate the relative risk for coeliac disease for children below 2 years of age by season of birth, also taking into account gender and time period of diagnosis. SETTING: Sweden. PARTICIPANTS: All 2151 children in the study base with verified coeliac disease. MAIN RESULTS: The risk for coeliac disease was significantly higher if born during the summer as compared with the winter (RR=1.4, 95% CI 1.2 to 1.7), but only in children below 2 years of age at diagnosis. This relative seasonal risk pattern prevailed during a 10 year epidemic of coeliac disease, although incidence rates varied threefold. The incidence was constantly higher among girls as compared with boys, but boys showed a more pronounced seasonal variation in risk than girls. CONCLUSIONS: An increased coeliac disease risk in children born in the summer compared with the winter reflects causal environmental exposure(s) with a seasonal pattern. Infections might be the exposure of importance, either by means of a direct causal role and/or through interaction with other exposures, for example, gluten intake. However, non-infectious exposures should also be explored as possible contributing causal factors.

Adolescent↗

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.

Biopsy↗

The structure of truncated recombinant human bile salt-stimulated lipase reveals bile salt-independent conformational flexibility at the active-site loop and provides insights into heparin binding.

Human bile salt-stimulated lipase (BSSL), which is secreted from the pancreas into the digestive tract and from the lactating mammary gland into human milk, is important for the effective absorption of dietary lipids. The dependence of BSSL on bile acids for activity with water-insoluble substrates differentiates it from other lipases. We have determined the crystal structure of a truncated variant of human BSSL (residues 1-5.8) and refined it at 2.60 A resolution, to an R-factor of 0.238 and R(free) of 0.275. This variant lacks the C-terminal alpha-helix and tandem C-terminal repeat region of native BSSL, but retains full catalytic activity. A short loop (residues 115-126) capable of occluding the active-site (the active site loop) is highly mobile and exists in two conformations, the most predominant of which leaves the active-site open for interactions with substrate. The bile salt analogue 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonic acid (CHAPS) was present in the crystallisation medium, but was not observed bound to the enzyme. However, the structure reveals a sulfonate group from the buffer piperizine ethane sulfonic acid (PIPES), making interactions with Arg63 and His115. His115 is part of the active-site loop, indicating that the loop could participate in the binding of a sulphate group from either the glycosaminoglycan heparin (known to bind BSSL) or a bile acid such as deoxycholate. Opening of the 115-126 active-site loop may be cooperatively linked to a sulphate anion binding at this site. The helix bundle domain of BSSL (residues 319-398) exhibits weak electron density and high temperature factors, indicating considerable structural mobility. This domain contains an unusual Asp:Glu pair buried in a hydrophobic pocket between helices alpha(H) and alpha(K) that may be functionally important. We have also solved the structure of full-length glycosylated human BSSL at 4.1 A resolution, using the refined coordinates of the truncated molecule as a search model. This structure reveals the position of the C-terminal helix, missing in the truncated variant, and also shows the active-site loop to be in a closed conformation.

Animals↗

Do human bile salt stimulated lipase and colipase-dependent pancreatic lipase share a common heparin-containing receptor?

Bile salt stimulated lipase (BSSL), a lipolytic enzyme secreted with pancreatic juice and with human milk, is in concert with colipase-dependent pancreatic lipase, important for the intestinal digestion of dietary lipids. BSSL may also facilitate uptake of free cholesterol from the intestinal lumen, while colipase-dependent lipase has a similar role for fatty acids. According to this theory, the two lipases bind to the intestinal mucosa via a common heparin-involving receptor. In the present study, binding of the two lipases to heparin was explored in vitro using purified human lipases and heparin molecules varying in both chain length and charge density. Native, but not denatured, BSSL bound avidly to heparin and several of the heparin variants. In contrast, at physiologic salt concentration, colipase-dependent lipase did not bind to heparin. Thus, our data do not support the view that the two lipases share a common intestinal heparin-like receptor. Hence, it seems unlikely that such binding could be of physiologic relevance for colipase-dependent lipase, although for BSSL the data are supportive.

Albumins↗

Coeliac disease: effect of early feeding on the incidence of the disease.

Coeliac disease, also called permanent gluten sensitive enteropathy, has recently been recognised as constituting a widespread health problem. Effective treatment involves the strict exclusion of wheat, rye, barley and possibly also oats from the diet. Genetic susceptibility and the presence of gluten in the diet are prerequisites for developing the disease. Sweden has recently experienced an epidemic of coeliac disease in children below 2 years of age. Previously, considerable changes in incidence over time have also been reported from England, Scotland and Ireland. Such obvious changes in incidence over rather short time periods, in genetically stable populations, emphasise the importance of environmental factors in the aetiology. Thus, most likely, the aetiology of coeliac disease is multifactorial. However, further conclusive evidence is required to settle if environmental factors, beyond presence of gluten in the diet, really influence the immunological process resulting in the coeliac small intestinal lesion, or merely influence the clinical expression of the disease. The search for contributing exposures has thus far focused on early feeding, suggesting that breast-feeding duration and the amount of gluten consumed are of importance, and possibly also the age for introducing gluten into the diet of infants. The pattern of causation may vary over time and between countries, however, which may obscure the search for risk factors. Nevertheless, a challenging possibility that needs to be explored is if coeliac disease can be delayed, or possibly even prevented for an entire life span, by favourable dietary habits.

Breast Feeding↗

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.

Adult↗

Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age.

OBJECTIVE: The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different populations. STUDY DESIGN: In a randomized, placebo-controlled, masked clinical trial, we assigned term Swedish (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron, 6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breast-fed exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months, the effect of iron (group 1 vs 2 + 3) was significant and similar in both populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9 months, the effect (group 2 vs group 3) was significant and similar at both sites for all iron status variables except hemoglobin, for which there was a significant effect only in Honduras. In Honduras, the prevalence of iron deficiency anemia at 9 months was 29% in the placebo group and 9% in the supplemented groups. In Sweden, iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION: Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants. The unexpected hemoglobin response at 4 to 6 months in both populations suggests that regulation of hemoglobin synthesis is immature at this age.

Age Factors↗

Is there a relation between docosahexaenoic acid concentration in mothers' milk and visual development in term infants?

BACKGROUND: Docosahexaenoic acid (DHA), present in high concentrations in the brain and retina, has a role in visual development. DHA is present in human milk, but not in most infant formulas. It is, however, under discussion whether DHA should be added to formulas intended for term infants. The concentration of DHA in human milk, which is influenced by maternal diet, varies considerably, but it is unknown whether this variation affects visual development in term infants. METHODS: The authors investigated 39 4-month-old fully breast-fed term infants in a cross-sectional study. Visual acuity was measured by swept visual evoked potentials, milk DHA was determined by gas chromatography, and maternal fish intake was assessed by a frequency questionnaire. RESULTS: Frequency of fish intake correlated positively to the DHA level in breast-milk (P = 0.001). Mothers who ate fish the day before sampling had a milk DHA level higher than expected from habitual fish intake (P = 0.002). If this was taken into account, 57% of the variation in milk DHA could be explained by fish intake. Multiple linear regression analysis revealed a significant association between visual acuity and milk DHA (P = 0.02, R2 = 0.09). CONCLUSION: This finding suggests a cause-and-effect relationship between infant milk DHA intake and visual acuity. If these data are confirmed, there is a need to consider the optimal intake of DHA for the lactating mother.

Animals↗

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.

Adolescent↗

Does breast-feeding affect the risk for coeliac disease?

Coeliac disease, or permanent gluten sensitive enteropathy, has emerged as a widespread health problem. It is considered an immunological disease, possibly of autoimmune type, albeit strictly dependent on the presence in the diet of wheat gluten and similar proteins from rye and barley. There are reasons to believe that the aetiology of coeliac disease is multifactorial, i.e. that other environmental exposures than the mere presence in the diet of gluten affect the disease process. Our studies have shown that prolonged breast-feeding, or perhaps even more important, ongoing breast-feeding during the period when gluten-containing foods are introduced into the diet, reduce the risk for coeliac disease. The amount of gluten consumed is also of importance in as much as larger amounts of gluten-containing foods increase the risk for coeliac disease, while it still is uncertain if the age for introducing gluten into the diet of infants is important. Thus, a challenging possibility, that need to be further explored, is if the coeliac enteropathy can be postponed, or possibly even prevented for the entire life span, by favourable dietary habits early in life.

Age Factors↗

Lactoferrin is responsible for the fungistatic effect of human milk.

Human milk has recognized anti-microbial effects and it has been repeatedly shown that breast-fed infants have fewer and less severe infections than formula-fed infants. While most studies have focused on anti-bacterial and anti-viral activities few have focused on the anti-fungal effect of human milk. Dermal and other infections caused by fungi are common in very low birth weight (VLBW) infants. Using a liquid culturing method and Candida albicans and Rhodotorula rubra as representative fungi, we studied the anti-fungal effect of human milk and certain human milk proteins. In vitro, human milk showed potent inhibitory effect on fungal growth. Most, if not all of this effect was caused by lactoferrin via its iron-binding capacity; increasing the iron content of the incubation medium abolished the inhibitory effect. In contrast, other human milk proteins with known or suggested anti-microbial effects rather increased fungal growth. Viability test and electron microscopy revealed that the growth inhibitory effect of human milk, i.e. mediated by lactoferrin, is fungistatic rather than fungicidal.

Antifungal Agents↗

Epidemic of coeliac disease in Swedish children.

Coeliac disease has emerged as a public health problem. The aim of the present study was to analyse trends in the occurrence of symptomatic coeliac disease in Swedish children from 1973 to 1997, and to explore any temporal relationship to changes in infant dietary patterns. We established a population-based prospective incidence register of coeliac disease in 1991, and, in addition, retrospective data from 1973 were collected. A total of 2151 cases fulfilled the diagnostic criteria. Furthermore. We collected national data on a yearly basis on duration of breastfeeding, intake of gluten-containing cereals and recommendations on when and how to introduce gluten into the diet of infants. From 1985 to 1987 the annual incidence rate in children below 2 y of age increased fourfold to 200-240 cases per 100000 person years, followed from 1995 by a sharp decline to the previous level of 50-60 cases per 100000 person years. This epidemic pattern is quite unique for a chronic disease of immunological pathogenesis, suggesting that prevention could be possible. The ecological observations made in this study are compatible with the epidemic being the result, at least in part, of a change in and an interplay among three factors within the area of infant feeding, i.e. amount of gluten given, age at introduction of gluten, and whether breastfeeding was ongoing or not when gluten was introduced. Other factor(s) may also have contributed, and the search for these should be intensified.

Adolescent↗

Crystallization and preliminary X-ray analysis of native and recombinant human bile-salt dependent lipase: strategies for improvement of diffraction quality.

Human bile-salt dependent lipase (BSDL), secreted into both the digestive tract and human milk, is integral to the effective absorption of dietary lipids. In attempts to obtain crystals suitable for high-resolution X-ray crystallographic studies, various forms of the enzyme have been crystallized, including native and desialidated human milk BSDL and both intact recombinant BSDL and a truncated form lacking the heavily glycosylated C-terminal repeat region. Trigonal crystals of native BSDL, with unit-cell parameters a = b = 90.0, c = 156.1 A, were obtained using 15-20%(w/v) PEG 8000 as precipitant. These crystals diffract to 3.5 A along the unique axis, but to only 5-7 A in orthogonal directions. Crystals of recombinant truncated BSDL grown from 15-20%(w/v) PEG 6000 are orthorhombic, space group P2(1)2(1)2(1), with unit-cell parameters a = 59.2, b = 90.0, c = 107.7 A, and diffract to 2.6 A resolution. These are suitable for structural analysis by X-ray crystallography.

Crystallization↗