Assessing the incidence trend and characteristics of eosinophilic esophagitis in children in Olmsted County, Minnesota.

Previous studies reported increased eosinophilic esophagitis (EoE) incidence in children. It is unclear whether this reported increased EoE incidence is true or due to increased recognition and diagnostic endoscopy among children. A population-based study that evaluated EoE incidence in OC, Minnesota, from 1976 to 2005 concluded that EoE incidence increased significantly over the past three 5-year intervals (from 0.35 [range: 0-0.87] per 100,000 person-years for 1991-1995 to 9.45 [range: 7.13-11.77] per 100,000 person-years for 2001-2005). The aim of this study is to assess the change of incidence and characteristics of EoE in children in the same population between 2005 and 2015 and compare the findings to those reported in the previous study. We retrospectively reviewed the electronic medical records from Olmsted Medical Center and Mayo Clinic between 2005 and 2015, using Rochester Epidemiology Project (REP) resources. All children with EoE diagnosis based on the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) guidelines were included. The incidence and characteristics of children with EoE during the study period were compared to those diagnosed between 1995 and 2005. The incidence of EoE in children adjusted for age and sex was 5.31 per 100,000 population person-years in 1995, 15.2 in 2005, and 19.2 in 2015. Change in annual incidence and seasonal variation were not significant, (P = .48) and (P = .32), respectively. Between 2005 and 2015, 73 children received an EoE diagnosis (boys 49; 67%) compared to 16 children (boys 10; 62.5) between 1995 and 2005. Mean (SD) age at diagnosis was 7.5 (5.2) and 12.8 (4.3) years, respectively. Symptoms differed by age of presentation, with vomiting the most common in children younger than 5 years (41.1% and 43.5%) and dysphagia in those older than 5 years (35.6% and 60.9%). The incidence of EoE was not increased for any specific age-group during the study period (P = .49). This study showed increased incidence of EoE in children in Olmsted County between 2005 and 2015 compared to the incidence between 1995 and 2005 (5.31 per 100,000 population person-years in 1995, 15.2 in 2005, and 19.2 in 2015). However, between 2005 and 2015, the change of incidence was not statically significant, (P = .48) despite the steady increase of EGD performed during the same time frame (64 in 2005 to 144 in 2015). By comparing children diagnosed between 2005 and 2015 to those diagnosed between 1995 and 2005, the mean age at diagnosis was younger in the former group, 7.5 versus 12.8 years. Vomiting replaced dysphagia as the most common clinical presentation. Otherwise, the presenting symptom of EoE in children remained consistent across specific age groups.

An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated beta-sheet structure for amyloid.

X-ray diffraction and other biophysical tools reveal features of the atomic structure of an amyloid-like crystal. Sup35, a prion-like protein in yeast, forms fibrillar amyloid assemblies intrinsic to its prion function. We have identified a polar peptide from the N-terminal prion-determining domain of Sup35 that exhibits the amyloid properties of full-length Sup35, including cooperative kinetics of aggregation, fibril formation, binding of the dye Congo red, and the characteristic cross-beta x-ray diffraction pattern. Microcrystals of this peptide also share the principal properties of the fibrillar amyloid, including a highly stable, beta-sheet-rich structure and the binding of Congo red. The x-ray powder pattern of the microcrystals, extending to 0.9-A resolution, yields the unit cell dimensions of the well-ordered structure. These dimensions restrict possible atomic models of this amyloid-like structure and demonstrate that it forms packed, parallel-stranded beta-sheets. The unusually high density of the crystals shows that the packed beta-sheets are dehydrated, despite the polar character of the side chains. These results suggest that amyloid is a highly intermolecularly bonded, dehydrated array of densely packed beta-sheets. This dry beta-sheet could form as Sup35 partially unfolds to expose the peptide, permitting it to hydrogen-bond to the same peptide of other Sup35 molecules. The implication is that amyloid-forming units may be short segments of proteins, exposed for interactions by partial unfolding.

The 1.7 A crystal structure of BPI: a study of how two dissimilar amino acid sequences can adopt the same fold.

We have extended the resolution of the crystal structure of human bactericidal/permeability-increasing protein (BPI) to 1.7 A. BPI has two domains with the same fold, but with little sequence similarity. To understand the similarity in structure of the two domains, we compare the corresponding residue positions in the two domains by the method of 3D-1D profiles. A 3D-1D profile is a string formed by assigning each position in the 3D structure to one of 18 environment classes. The environment classes are defined by the local secondary structure, the area of the residue which is buried from solvent, and the fraction of the area buried by polar atoms. A structural alignment between the two BPI domains was used to compare the 3D-1D environments of structurally equivalent positions. Greater than 31% of the aligned positions have conserved 3D-1D environments, but only 13% have conserved residue identities. Analysis of the 3D-1D environmentally conserved positions helps to identify pairs of residues likely to be important in conserving the fold, regardless of the residue similarity. We find examples of 3D-1D environmentally conserved positions with dissimilar residues which nevertheless play similar structural roles. To generalize our findings, we analyzed four other proteins with similar structures yet dissimilar sequences. Together, these examples show that aligned pairs of dissimilar residues often share similar structural roles, stabilizing dissimilar sequences in the same fold.

Pyloric channel stricture secondary to high-dose ibuprofen therapy in a patient with cystic fibrosis.

OBJECTIVE: To describe a case of pyloric channel stricture secondary to high-dose ibuprofen therapy in a pediatric patient with cystic fibrosis. CASE SUMMARY: A 12-year-old white girl started taking high-dose ibuprofen to treat the pulmonary manifestations of cystic fibrosis. The peak plasma concentration at dose initiation was within the accepted therapeutic range. Approximately one month later, the patient developed emesis and intolerance of solid foods, which persisted for several months and resulted in a weight loss of seven kilograms. The patient was referred to a pediatric gastroenterologist, who performed an upper endoscopy and subsequently diagnosed a pyloric channel stricture. The patient's pyloric channel was successfully dilated with two balloons. It is felt that the pyloric stricture developed from healing antral/pyloric channel ulcers. Ibuprofen was discontinued and omeprazole therapy was begun. Over the course of the following year, the patient was asymptomatic. Follow-up upper gastrointestinal barium swallows were normal. DISCUSSION: When used for analgesia and fever in the pediatric population, ibuprofen has been shown to be a relatively safe drug. While it is known that ibuprofen may cause gastrointestinal adverse effects, the pediatric population is at lower risk; however, large doses of ibuprofen increase the risk of gastrointestinal adverse effects. The use of large doses of ibuprofen in the treatment of cystic fibrosis is a relatively new therapy. Limited data thus far in cystic fibrosis patients do not suggest increased risk of gastrointestinal complications. CONCLUSIONS: Limited data to date indicate that ibuprofen, when used in large doses to treat the pulmonary manifestations of cystic fibrosis, is relatively safe. However, because of the potential risks to the gastrointestinal tract of high-dose ibuprofen therapy, clinicians should be aware of its possible complications.

Obesity in children and adolescents.

The prevalence of obesity in children and adolescents is increasing. For those whose weight is greater than or equal to 120% IBW a thorough evaluation is needed to determine the etiology. The majority of children will have exogenous obesity and will not require extensive diagnostic testing. Complications of obesity occur in children and adolescents with psychosocial being one of the more severe. Treatment is necessary to prevent complications and the only treatment that has been shown to be successful is a multidisciplinary family approach with long-term follow-up. The once a day pill to treat obesity is far in the future.

[The walking-through phenomenon in arterial occlusive disease]. / Zum Phänomen des walking-through bei arterieller Verschlusskrankheit.

In order to assess the metabolic effects of walking-through phenomenon during treadmill exercise the fluctuations of lactate and pyruvate concentration in arterial and popliteal venous blood and the changes in the lactate pyruvate ratio were studied in seven patients with arterial occlusive disease. During exercise, significant differences in venous lactate, lactate pyruvate ratio and arterial venous differences in lactate were found in patients with walking-through phenomenon. It is concluded that the rate of anaerobic glycolysis is reduced in patients with walking-through phenomenon.

Computed three-dimensional reconstruction of median-eminence capillary modules: image alignment and correlation.

Image alignment is an absolute requirement for three-dimensional (3-D) reconstruction from serial sections, and Fourier correlation is the most powerful way to compute alignments. The rotational and translational components of misalignment can be corrected by an iterative correlation procedure, but for images having significant differences, alignment can fail with a likelihood proportional to the extent of the differences. We found that translational correction was determined much more reliably when low-pass filters were applied to the product transforms from which the correlations were calculated. Rotational corrections based on polar analyses of the auto-correlations of the images instead of on the images directly contributed to more accurate alignments. These methods were used to generate 3-D reconstructions of brain capillary modules from serial-section mosaics of digitized transmission electron micrographs.

Long-term complications of arteriohepatic dysplasia.

PURPOSE: It has been stated that arteriohepatic dysplasia is a form of biliary paucity with a good prognosis. We wished to determine the long-term morbidity and mortality associated with arteriohepatic dysplasia. PATIENTS AND METHODS: The charts of all patients with arteriohepatic dysplasia followed by the pediatric gastroenterologists of the University of Minnesota into adulthood were reviewed. RESULTS: Over the last 33 years, the pediatric gastroenterologists have followed 16 children with syndromic paucity, six of whom are now beyond age 18 years. Although five of six patients responded to medical therapy with improvement in their cholestasis and appeared stable clinically through childhood, five of six patients had complications of arteriohepatic dysplasia after age 16 years that resulted in severe morbidity (three) or death (two). These complications included hepatic failure (two), renal failure (one), cerebellar herniation (one), and hepatocellular carcinoma (one). In only one patient were symptoms of the complications present prior to the age of 18 years. CONCLUSION: As more patients with arteriohepatic dysplasia reach adulthood, it appears that this syndrome may be accompanied by long-term manifestations extending beyond childhood. It is important that physicians assuming management of these patients from pediatricians be aware that new abnormalities may appear without warning and that the hepatic disease may deteriorate despite apparent stability through childhood.

Design and use of PET tomographs: the effect of slice spacing.

With modern positron tomographs producing 14, 21, or more transaxial slices, the effects of slice spacing on quantitative reconstruction and three-dimensional displays must be evaluated. This analysis can be approached in terms of the partial volume effect, quantified by the recovery coefficient, or in terms of sampling theory leading to the concept of aliasing. The axial recovery coefficient varies as a function of the position of an object in relation to the slices, with greater variability for larger slice spacings and finer axial resolutions. The aliased image power varies in the same way. The variability in the recovery coefficient and aliasing increase when smaller objects are imaged. Tomographs should be designed with slice spacing approximately half the full-width at half-maximum axial resolution of the tomograph; finer spacing does not appear to confer significant advantages. Thus, quantification and display in positron tomography depend on slice spacing, resolution, and object size.

Three-dimensional display of positron emission tomography of the heart.

A method for producing images of 82Rb myocardial perfusion and 11C carbon monoxide gated blood pool images is described. In the case of 82Rb images, cylindrical projection displaying myocardial activity as viewed from the side is presented to complement the polar projection. Cubic display of the conventional short- and long-axis slices is described that permits interactive selection of any desired slices. A three-dimensional cine display of the left ventricle rotating about its long axis is produced that gives a very realistic presentation of myocardial activity. Very similar processing techniques are applied to gated carbon-11 blood-pool studies to yield beating images of the surface of the blood pool in multiple projections.

Significance of non-pneumophila Legionella species in adult community-acquired and nosocomial pneumonias.

The number of different Legionella species is increasing at an impressive rate. In two prospective studies, one involving 110 intensive-care unit (ICU) patients with mainly nosocomial pneumonias and the other 105 patients with community-acquired pneumonias, we investigated the incidence and significance of Legionella pneumophila and non-pneumophila pneumonias on the basis of 17 different main serogroups. In the first study, 14 ICU patients had 15 (13.6%) Legionella pneumonias, which, in 5 cases (33%), were of non-pneumophila etiology. In the second study, 9 patients with community-acquired pneumonias had 10 (9.5%) Legionella pneumonias. Leading this study were 6 L. gormanii infections, followed by 2 L. dumoffii and only 1 L. pneumophila and 1 L. longbeachae pneumonia. Of the total, 22 of 23 patients with Legionnaires' disease suffered from severe basic diseases and complications (acute renal failure, respiratory insufficiency, etc.) predominant among the nosocomial pneumonias. The mortality rate was significant in these patients at 33% (5 patients) in the ICU group and 10% (1 patient) in the group with community-acquired pneumonias. We conclude that non-pneumophila Legionella species should receive more diagnostic and therapeutic consideration in patients with nosocomial or community-acquired pneumonias.