bluuebunny/crossref_metadata_2025 huggingface dataset:
Serial Changes in Titers of Antibody to Hepatitis B Surface Antigen After Immunization of Infants Born to Mothers with Hepatitis B e Antigen
Authors: Fujisawa Tomoo , Onoue Masahiro , Inui Ayano , Kosugi Takeshi
Published: February 2024

To evaluate the long‐term protection provided by hepatitis B (HB) vaccine in a high‐risk environment, we followed 50 infants born to mothers with hepatitis B e (HBe) antigen. These infants were immunized with a three‐dose regimen of plasma‐derived HB vaccine and were followed for up to 10 years. Two infants (4%) acquired hepatitis B virus (HBV) infection before 1 year of age. The 48 other infants remained hepatitis B surface (HBs) antigen‐negative during the follow‐up period. The geometric mean titers of serum antibody to HBs antigen rapidly decreased during the first 4 years but remained at protective levels throughout the follow‐up period. These data suggest that protection against significant HBV infection lasts for at least 10 years. We conclude that the long‐term protection afforded by plasma‐derived HB vaccine is satisfactory and that a routine booster dose before 10 years of age is not necessary.
Fecal Short‐Chain Fatty Acids in Patients with Diarrhea‐Predominant Irritable Bowel Syndrome: In Vitro Studies of Carbohydrate Fermentation
Authors: Treem William R. , Ahsan Naheedt , Kastoff Geraldine , Hyams Jeffrey S.
Published: February 2024

Colonic bacterial production of short‐chain fatty acids (SCFA) plays an important role in the salvage of unabsorbed carbohydrate and in colonic absorption of electrolytes and water. The objective of this study was to determine whether patients with diarrhea‐predominant irritable bowel syndrome (DP‐IBS) have a different pattern and rate of fermentation of carbohydrate and fiber to SCFA compared with controls. Fecal homogenates from 10 patients with DP‐IBS and 10 age‐matched controls were studied. SCFA were measured by gas chromatography in baseline fecal samples and in fecal homogenates in an in vitro anaerobic fermentation system after incubation with no additional substrate, lactulose, potato starch, citrus pectin, and hemicellulose over a 24‐hour period. Net SCFA production rates were calculated for the first 6 h of the incubation period. Patients with DP‐IBS had a consistently different pattern of less total SCFA, a lower percentage of acetate (p < 0.05), and a higher proportion of n‐butyrate (p < 0.05) than controls. In stool homogenates from both controls and DP‐IBS patients, lactulose fermentation resulted in the highest rate of SCFA production followed by pectin, starch, and hemicellulose. However, at all time points, the fecal homogenates from controls generated a higher concentration of total SCFA, acetate, and propionate with all substrates tested. SCFA production rates were higher in controls incubated with lactulose, starch, and hemicellulose. The fecal SCFA profile of patients with DP‐IBS is characterized by lower concentrations of total SCFA, acetate, and propionate and a higher concentration and percentage of n‐butyrate. Fecal flora from these patients produced less SCFA in an in vitro fermentation system in response to incubations with various carbohydrates and fibers. Differences in SCFA production by colonic bacterial flora in patients with DP‐IBS may be related to the development of gastrointestinal symptoms.
Restoration of Body Composition in Celiac Children after One Year of Gluten‐Free Diet
Authors: Rea Francesco , Polito Cesare , Marotta Antonio , Di Toro Antonino , Iovene Antonio , Collini Rosaria , Rea Luciana , Sessa Giuseppa
Published: February 2024

Restoring protein, fat, and bone compartments in celiac children on a gluten‐free diet (GFD) is not yet well understood. Hence, anthropometric, biochemical, and bone densitometric assessment was performed in 23 celiac children, 8 boys and 15 girls, aged 1 to 12 years (mean 4.7), at diagnosis and 1 year after GFD. At diagnosis the patients had height, arm muscle area, triceps skinfolds, subscapular skinfolds, fat area index, and bone mineral content significantly lower than in an age‐ and sex‐matched control group. After 1 year on GFD, no significant difference was found between patients and controls in all the parameters studied except in height and arm muscle area, which, however, were very near to the normal expected. Serum hemoglobin, iron, and zinc values were below the normal range in more than one half of patients at diagnosis and within the normal range in almost all of them after 1 year of GFD. Serum hemoglobin, iron, zinc, triglycerides, proteins, albumin, and calcium values significantly rose during the year of GFD. A year of GFD in celiac children allows a virtually complete return in body mass composition.
Evaluation of Intranasal Midazolam in Children Undergoing Esophagogastroduodenoscopy
Authors: Fishbein Mark , Lugo Ralph A. , Woodland Jennifer , Lininger Barbara , Linscheid Tom
Published: February 2024

Background:

Intravenous midazolam and opioids are used to produce conscious sedation in children undergoing esophagogastroduodenoscopy (EGD). However, children may experience significant fear and anxiety before receiving these medications, especially during separation from parents and during venipuncture. Intranasal administration of midazolam represents a noninvasive method of sedating children before anxiety‐producing events. The objective of this study was to determine whether premedication with intranasal midazolam reduces stress and anxiety of separation from parents and of undergoing venipuncture, while maintaining adequate sedation during EGD.

Methods:

This was a prospective, randomized, double‐blind study in 40 children, aged 2 to 12 years, who were undergoing EGD. Patients in group I were premedicated with intranasal placebo (0.9% NaCl) followed 10 minutes later by intravenous midazolam (0.05 mg/kg) and intravenous meperidine (1 mg/kg). Patients in group II were premedicated with intranasal midazolam (0.2 mg/kg) followed by intravenous placebo (0.9% NaCl) and intravenous meperidine (1 mg/kg). Anxiolysis and sedation were scored by a blinded observer, who identified minor and major negative behaviors during four observation periods: intranasal drug administration, separation from parents, venipuncture, and EGD.

Results:

Premedication with intranasal midazolam significantly reduced negative behaviors during separation from parents (p < 0.05); however, no difference between regimens was noted during venipuncture or EGD. Negative behaviors appeared to increase during administration of intranasal midazolam or placebo.

Conclusions:

Premedication with intranasal midazolam is effective in reducing negative behaviors during separation from parents, while it maintains sedation during the endoscopic procedure. The benefits of intranasal administration may be negated, however, by irritation, and discomfort caused by intranasal drug delivery.
Mucosal Inflammation in Pediatric Diversion Colitis: A Quantitative Analysis
Authors: Grant Neil J. , Van Kruiningen Herbert J. , Haque Salima , West A. Brian
Published: February 2024

Background:

Diversion colitis commonly occurs in bypassed segments of colorectum, and has been described qualitatively in Hirschsprung's disease patients with colostomies. The objective of this study was to characterize quantitatively the changes in the inflammatory cell population in the mucosa of children with diversion colitis.

Methods:

Paraffin blocks of well‐oriented, full‐thickness colorectal tissues were obtained from 15 children with diversion colitis (all with Hirschsprung's disease), four pediatric controls and four adult controls. Sections were immunostained for B and T lymphocytes, macrophages, IgG, IgM, and IgA. Measurements were made referent to a standard length of muscularis mucosae. Lymphoid follicles were counted and the areas occupied by B and T cells were determined by image analysis. Cells in the interfollicular lamina propria were counted separately, but IgA‐containing plasma cells were too abundant to enumerate.

Results:

Pediatric diversion colitis was characterized by enlarged and more numerous lymphoid follicles with approximately four times as many B lymphocytes and twice as many T lymphocytes in the follicular compartment of the mucosa when compared to pediatric controls. The interfollicular mucosa was thickened (499 ± 27 versus 380 ± 56 μm) and contained approximately six times as many B cells and eight times as many T cells as controls. Macrophages and plasma cells containing IgG and IgM were not significantly increased.

Conclusions:

These findings extend the qualitative observations of increased follicular and lamina propria lymphoid tissue in bypassed segments of colon, and are consistent with the hypothesis of persistent antigenic stimulation of the mucosa‐associated lymphoid tissue.
The Effect of Starvation on Brain Carnitine Concentration in Neonatal Rats
Authors: Murakami Ryusuke , Tanaka Akiyoshi , Nakamura Hajime
Published: February 2024

Background

We examined carnitine concentrations in fasted neonatal rat brain to evaluate the effect of starvation on fatty acid metabolism.

Methods

The free‐ and acylcarnitine concentrations in neonatal rat brain and heart were determined after a 72‐hour starvation period from the 3rd to 6th postnatal day. They were also determined in rats at 3 and 6 days of age fed normally by the mother rats as controls.

Results

In the brain, the mean free carnitine concentration in the fasted group showed an increase similar to that in normal rats and there was no difference between the fasted and 6‐day‐old control rats. However, the mean acylcarnitine concentration was significantly higher in the fasted group than in the control group at both 3 and 6 days of age. Almost all of the increased acylcarnitine in the fasted group was short‐chain acylcarnitine.

In the heart, there was no difference in the mean free carnitine concentration between the fasted group and control group at 6 days of age. The 6‐day‐old rats in both the fasted and control groups showed higher levels compared to 3‐day‐old rats in the control group. The mean acylcarnitine concentration in the fasted group was not different from that in control group at 6 days of age, while the amount of short‐chain acylcarnitine was less than that in the control group at 6 days of age.

Conclusions

These findings suggest that in the brain, carnitine is accumulated as a result of redistribution during starvation, and is utilized for energy supply by fatty acid oxidation.
Circulating Oxyntomodulin‐like Immunoreactivity in Healthy Children and Children with Celiac Disease
Authors: Le Quellec Alain , Clapié Marjorie , Callamand Pierre , Lehmann Michel , Kervran Alain , Bataille Dominique , Rieu Daniel
Published: February 2024

Background:

The aim of the study was to evaluate the new hormonal entity oxyntomodulin‐like immunoreactivity in malabsorption states, and to assess its potential in celiac disease management.

Methods:

We measured basal and postprandial oxyntomodulin‐like immunoreactivity values in 35 children divided into 3 groups: group 1 was composed of 13 children with celiac disease, either under a gluten‐free diet (8 patients) or normal diet (5 patients); group 2 was composed of 8 children hospitalized for gastroenteritis or chronic diarrhea, without biological evidence of malabsorption nor abnormal jejunal mucosa; group 3 was composed of 22 control subjects.

Results:

Fasting and meal‐stimulated levels in the control group were 71 ± 10 and 130 ± 26 pmol/l, respectively. Mean concentrations were elevated in patients with celiac disease (basal = 349 ± 254 pmol/l, postprandial = 446 ± 332 pmol/l) and in the group 2 (basal = 139 ± 58 pmol/l, postprandial = 218 ± 85 pmol/l), but the difference with control subjects did not reach statistical significance. In children with celiac disease, basal and stimulated values correlated with the degree of malabsorption as assessed by hemoglobin (p = 0.006 and p = 0.01, respectively) and serum folate concentrations (p = 0.03 and p = 0.02, respectively).

Conclusions:

Oxyntomodulin‐like immunoreactivity is noticeably higher in healthy children than previously measured in healthy adult subjects. This hormonal parameter is not an adequate diagnostic tool in celiac disease. Nevertheless, in the context of celiac disease, its elevation reflects the degree of malabsorption and may provide a quantitative approach of the extent of mucosal damage.
Digestion of Ceramide by Human Milk Bile Salt‐Stimulated Lipase
Authors: Nyberg Lena , Farooqi Aijaz , Bläckberg Lars , Duan Rui‐Dong , Nilsson Åke , Hernell Olle
Published: February 2024

Background:

There is a renewed interest in metabolism of sphingolipids because of their role in signal transduction. Sphingomyelin is the dominating phospholipid in human milk but its metabolism and possible function in the gastrointestinal tract of breast fed infants is unknown. We explored whether bile salt‐stimulated milk lipase has a role in sphingolipid metabolism.

Methods:

In vitro assays of sphingomyelinase and ceramidase activities, using radiolabeled substrates, human milk samples and purified native and recombinant variants of bile salt‐stimulated milk lipase with or without known activators or inhibitors.

Results:

Human whey and purified lipase catalysed hydrolysis of palmitoyl‐labeled ceramide with the highest rate around pH 8.5‐9.0. 1 mg of lipase hydrolysed 0.7 µmol ceramide in one hour at pH 8.5 in presence of 4 mM bile salt. The activity of whey was inhibited by antibodies towards human bile salt‐stimulated milk lipase, indicating that this lipase accounted for virtually all ceramidase activity in the milk. In contrast, bile salt‐stimulated milk lipase showed no activity against sphingomyelin. However we give evidence of a separate, hitherto unknown, acid sphingomyelinase in human milk. Under the used in vitro conditions this sphingomyelinase could account for hydrolysis of half of milk sphingomyelin in one hour.

Conclusions:

Human milk bile salt‐stimulated milk lipase hydrolyses ceramide and may thus have a role in sphingomyelin digestion, but only after initial hydrolysis to ceramide and phosphorylcholine. Part of the latter could be carried out in the stomach by the acid milk sphingomyelinase now described. We speculate that these two milk enzymes may be of importance for optimal use of human milk sphingolipids.
Accuracy of the [13C]‐Urea Breath Test in Diagnosing Helicobacter pylori Gastritis in Pediatric Patients
Authors: Delvin Edgard E. , Brazier Jean L. , Deslandres Collete , Alvarez Fernando , Russo Pierre , Seidman Ernest
Published: February 2024

Background:

The causal association between Helicobacter pylori (H. pylori) colonization of the gastric mucosa and gastritis is now well established. Histologic examination of endoscopic biopsy specimens has long been regarded as the gold standard for diagnosis. However, the changes can be focal in nature and presence of the organism may be missed in nonsampled areas. The urea breath test, which uses a stable isotope, offers distinct advantages, in that it is noninvasive and measures the activity of the micro‐organism. It thus represents a potentially invaluable tool in the initial diagnosis of the infection and in verifying its eradication.

Methods:

The study design was that of a prospective, blinded comparison of the [13C]‐urea breath test with histologic assessment of antral biopsy specimens using the Warthin‐Starry stain, to diagnose H. pylori infection in a group of 79 consecutive pediatric patients.

Results:

Patients classified as negative by histology (n = 67) had breath 13C enrichment of 0.97 ± 0.07 δ‰ (mean ± SEM), with a range of ‐0.20 and 2.83 δ‰. In contrast, those with a positive histologic results (n = 12) had an enrichment of 25.41 ± 5.01 δ‰ (range, 3.43‐58.80; p < 0.001). At the chosen cutoff point of 3 δ‰, the sensitivity and specificity as well as the positive and negative predictive values of the breath test were uniformly 100%.

Conclusion:

The [13C]‐urea breath test is a highly reliable, noninvasive method for the diagnosis of H. pylori gastritis in children and adolescents.
Helicobacter pylori Infection in Children with Celiac Disease: Prevalence and Clinicopathologic Features
Authors: Luzza Francesco , Mancuso Maria , Imeneo Maria , Mesuraca Luigi , Contaldo Antonio , Giancotti Laura , La Vecchia Anna M. , Docimo Corrado , Pensabene Licia , Strisciuglio Pietro , Pallone Francesco , Guandalini Stefano
Published: February 2024

Background:

Celiac disease is frequently associated with chronic gastritis. Helicobacter pylori is the main etiologic agent of chronic gastritis. The aim of this study was to assess the prevalence of H. pylori, the related symptoms, and the endoscopic and histologic gastric features in children with celiac disease.

Methods:

Eight‐one (24 boys, 57 girls; age range: 1.4‐17.7 years, median 6.8) children with celiac disease were studied. All children had a blood sample taken. In a subgroup of 30 children who underwent endoscopy, three gastric biopsy specimens were taken for histology (hematoxylin and eosin, Giemsa, immunohistochemistry) and urease quick test. Symptom complaints were recorded. Age‐ and sex‐matched (one case, one control) children without celiac disease were used for comparison. Serum H. pylori IgG were measured by means of a locally validated commercial enzyme‐linked immunoassay.

Results:

Overall, 15 of 81 (18.5%) children with celiac disease and 14 of 81 (17.3%) control children were positive for H. pylori. The percentage of H. pylori positivity was similar in children with untreated and treated celiac disease. Recurrent abdominal pain was the only symptom that helped to distinguish between H. pylori‐positive and H. pylori‐negative children. However, symptoms disappeared in patients with celiac disease after gluten withdrawal, irrespective of H. pylori status. All endoscopic (erythema, nodularity) and histologic (superficial‐, interstitial‐, lymphocytic‐gastritis, activity, lymphoid follicles) findings did not differ between celiac and nonceliac H. pylori‐positive children.

Conclusions:

Prevalence and clinical expressivity of H. pylori infection is not increased in children with celiac disease. The clinicopathologic pattern of the infection is not specifically influenced in this condition.
Home Parenteral Nutrition in Children: The Polish Experience
Authors: Ksiazyk Janusz , Lyszkowska Malgorzata , Kierkus Jaroslaw , Bogucki Krzysztof , Ratyńska Anna , Tondys Bozenna , Socha Jerzy
Published: February 2024

Background:

Home parenteral nutrition has become routine for management of intestinal failure in patients. In Poland the main obstacle to widespread use of home parenteral nutrition is the lack of interest of commercial companies in delivering feedings and ancillaries to patients.

Methods:

Twenty‐five home parenteral nutrition patients aged from 4 months to more than 13 years were reviewed. The mother or both parents were trained in home parenteral nutrition techniques for 4 to 6 weeks and compounded the nutrients themselves at home.

Results:

The mean duration of home parenteral nutrition was 10,117 patient days. Hospital stays of patients receiving parenteral feedings were significantly shorter than the duration of administration of home parenteral nutrition (p < 0.001). Eleven children are continuing the home parenteral nutrition program. Eighty‐three catheters were used in these patients. The rate of catheter occlusion decreased within the observation period, and in 1997 not one case of occlusion was observed. In 1997 only three catheters were removed during 7.8 patient years, and the overall incidence of catheter‐related complications was 0.38 per patient year. The overall occurrence of septicemia was one case in 516 days and of catheter infection was one in 459 days. In 1997 a catheter was infected on average of once every 1419 days. There was significant improvement in the z score for weight during therapy. The average monthly cost of nutrients and ancillary items was approximately $1200 (4200 Polish zlotys [PLN]). These costs are 1.6 to 3 times lower than those recorded in other studies.

Conclusion:

Home parenteral nutrition in children with nutrients mixed by caregivers in the home setting is a safe and appropriate method of treatment that can be used in countries where home parenteral nutrition solutions are not manufactured or where commercial home parenteral nutrition is not economically feasible.
The Effects of High‐Dose Ibuprofen and Pancreatic Enzymes on the Intestine of the Rat
Authors: Kimura Robert E. , Dy Sally Ann D. , Uhing Michael R. , Beno David W. A. , Jiyamapa Vanida A. , Lloyd‐Still John D.
Published: February 2024

Background:

High‐dose ibuprofen therapy limits the progression of lung disease in patients with cystic fibrosis. However, ibuprofen increases intestinal permeability, which potentiates intestinal damage caused by high‐dose pancreatic enzyme treatment, as was shown in a previous study by this group. In the present study, the combined effects of ibuprofen and pancreatic enzyme treatment on the intestine and liver were examined.

Methods:

Using a chronically catheterized rat model, high‐dose ibuprofen (60 mg/kg·day in two doses), with or without pancreatic enzyme treatment was infused into gastric and duodenal catheters, respectively, for 20 days. Six groups were studied: control group; ibuprofen treatment alone; pancreatic enzyme treatment alone (two groups: normal dose, 10,000 U lipase/kg·day and high dose, 40,000 U lipase/kg·day); and ibuprofen combined with pancreatic enzyme (two groups: ibuprofen with high‐dose pancreatic enzyme and ibuprofen and low‐dose pancreatic enzyme). After treatment, rats were autopsied, and complete histologic analyses of the entire intestine and liver were performed.

Results:

Ibuprofen caused mild ulceration of the small intestine in 50% of rats. Pancreatic enzyme treatment alone did not induce ulceration of the intestine. The combination of pancreatic enzyme and ibuprofen treatment increased the severity of the ulcers in the small intestine but not the number of ulcers or the percentage of rats affected. Ibuprofen treatment alone did not cause ulcers in the large intestine, but with the addition of pancreatic enzymes, ulceration and fibrosis were present.

Conclusions:

Ibuprofen at doses used to limit progression of cystic fibrosis lung disease caused enteropathy in 50% of rats. There was synergism between ibuprofen and pancreatic enzyme treatment in the production of severe ulcers. Ulcers in the cecum and colon were increased with combined ibuprofen and pancreatic enzyme treatment compared with incidence in control animals.
Sera of Children With Hepatitis C Infection and Anti‐Liver‐Kidney Microsome‐1 Antibodies Recognize Different CYP2D6 Epitopes Than Adults With LKM+/HCV+ Sera
Authors: Herzog Denise , Yamamoto Ana‐Maria , Jara Paloma , Maggiore Giuseppe , Sarles Jacques , Alvarez Fernando
Published: February 2024

Background:

Liver‐kidney microsome type 1 (LKM1) antibodies are specific markers of autoimmune hepatitis (AIH) type 2. Antibodies to LKM1 have been found in 2% to 3% of adults infected with hepatitis C virus (HCV) without AIH. Thirty percent of these antibodies are directed against linear sequences of CYP2D6 protein. LKM1 antibodies in HCV+/LKM1+ sera and in sera of AIH patients do not recognize the same CYP2D6 epitopes. The current study was conducted to determine whether LKM1 antibodies in HCV+/LKM1+ children's sera are the result of the same immune response as the antibodies described in AIH type 2 and in HCV+/LKM1+ adult patients.

Methods:

Sera from 10 HCV+/LKM1+ children were tested against human liver microsomal and cytosolic proteins by Western blot analysis and against synthetic peptides of the CYP2D6 sequence between amino acids 200 and 429 by dot blot. The same sera were tested against radiolabeled CYP2D6 by immunoprecipitation.

Results:

Four of 10 sera tested by Western blot analysis showed immunoglobulin (Ig) G‐type antibodies against CYP2D6, and 2 had antibodies against proteins of 58, 66, and 84 kDa. One of the sera also contained IgM‐type anti‐66‐kDa and 84‐kDa proteins. The radioligand test detected anti‐CYP2D6 antibodies in 9 of 10 patients. Five of the anti‐CYP2D6‐positive sera recognized a peptide between amino acids 200 and 429 including amino acids 254‐271.

Conclusions:

Most HCV+/LKM1+ sera from children recognize conformational epitopes of the CYP2D6 antigen, and half recognize linear epitopes. Some HCV+/LKM1+ sera demonstrated antibodies against the AIH type 2 main antigenic site of the CYP2D6. Screening of HCV RNA should be performed before starting treatment of presumed autoimmune hepatitis associated with LKM1.
Development and Subsequent Refinement of the Inflammatory Bowel Disease Questionnaire: A Quality‐of‐Life Instrument for Adult Patients with Inflammatory Bowel Disease
Authors: Irvine E. Jan
Published: February 2024

Background:

Health‐related quality of life (HRQOL) describes the physical, social, and emotional attitudes and behavior of people in relation to health status. By the 1980s, HRQOL was noted to be impaired in chronic diseases but inflammatory bowel disease, had not been extensively described.

Methods:

This review summarizes the results of several studies describing the development and application of a disease‐specific HRQOL instrument, the Inflammatory Bowel Disease Questionnaire (IBDQ).

Results:

An initial study described how patients with inflammatory bowel disease identified 150 problems they had experienced in four domains: bowel, systemic, emotional, and social function. Almost half of patients underreported impairment until encouraged by a reminder list. Thirty‐two questions were included in the final questionnaire and were scored on a 7‐point scale from 1 (worst) to 7 (best) for a range of possible scores from 32 to 224. Physicians' and spouses' global assessments correlated poorly with patient‐reported HRQOL. Subsequent validation of the IBDQ suggested a strong correlation with disease severity (r = ‐0.5; p < 0.001) and a test‐retest reliability of 0.7. Mean score changes of 16 to 30 points have been linked to changes in therapy. Statistically significant differences also occur between active and inactive disease. Results of four clinical trials have included the IBDQ as a measure of outcome. A self‐administered version and a shortened version of the IBDQ have also been validated.

Conclusions:

The IBDQ is a valid, reliable, and sensitive measure that can be meaningfully applied in clinical trials. The short IBDQ may also be useful in clinical research and office practice.
Periodic Acid–Schiff Staining Abnormality in Microvillous Atrophy: Photometric and Ultrastructural Studies
Authors: Phillips Alan D. , Szafranski Marian , Man Lai‐Yi , Wall Wilson J.
Published: February 2024

Background:

The accumulation of periodic acid Schiff (PAS)‐positive material in the epithelium in microvillous atrophy (MVA) is diagnostic but unexplained. It occurs earlier in the epithelial life cycle than the formation of microvillous inclusions and warrants further investigation.

Methods:

Scanning photometry was used to assess the distribution of the PAS‐positive material within epithelial cells and to assess how this changed with position on the crypt–villus axis. Thiery staining was applied to test the PAS positivity of the secretory granules, and quantitative ultrastructural morphometry was used to study secretory granule distribution in the epithelium.

Results:

The PAS abnormality arose in upper crypt epithelium in congenital and late‐onset MVA and continued up the villus. Thiery staining demonstrated that the secretory granules were PAS positive. Quantitative morphometry showed that secretory granules in congenital MVA were predominantly present in upper crypt and declined in the low villus. In late‐onset MVA, secretory granules arose in the upper crypt but predominated in the low villus region. No evidence of secretory granule coalescence with the apical membrane was seen, although evidence of crinophagy was observed. Secretory granule profiles were seen, indicating that they formed part of a membrane‐bound vesicular network within the cell, rather than existing simply as discrete bodies. The Golgi complex appeared normal.

Conclusions:

The secretory granules are responsible for the PAS‐positive staining in upper crypt and low villus regions in MVA. They appear to form an intracytoplasmic vesicular network, undergo crinophagy, and decline in prominence in the low to midvillous region. The absence of evidence of coalescence with the apical membrane indicates that the secretory granules arise from a post‐Golgi block in exocytosis rather than from endocytosis of gut luminal contents. Periodic acid–Schiff positivity in upper villous regions arises from microvillous inclusions and lysosomal bodies.
Food Protein‐Induced Enterocolitis Syndrome: Laboratory Perspectives
Authors: Dupont Christophe , Heyman Martine , Simpson Hugh A. , Anderson John A.
Published: February 2024

The expression of food protein allergy in man is very heterogeneous, varies with the age of the subject and is to a certain extent genetically determined. Skin prick tests with standardized food extracts are a sensitive method for detection of immunoglobulin E bound to reactive cells such as mast cells. Various tests on cellular immunity have been developed, especially because T‐cell mediated reactions are considered to play a role in mainly delayed gastrointestinal reactions to cow's milk proteins. Food allergy may involve the entire gut, from mouth to rectum, including the esophagus. Abnormalities in intestinal permeability are the hallmarks of the inflamed gut, and may contribute to diagnosis of food induced enteropathy. What determines the characteristics of the intestinal inflammatory response is largely the cytokine responses triggered by the pathologic mechanism, whatever its origin, in the stomach, the small intestine, and the colon. A so‐called T‐helper type 2 response is characteristic of the allergic subject. A secretion of tumor necrosis factor‐α alpha by blood cells of children allergic to milk was shown. All means of investigation may help in analyzing food substitutes for allergic infants.
Acid Secretion and Response to Pentagastrin or Omeprazole in Human Fetal Stomach Xenografts
Authors: Muhale Filipe , Morali Alain , Duprez Adrien , Lozniewski Alain , Angioï Karine
Published: February 2024

Background:

The dual capacity of stomach tissue to secrete acid and to respond to secretagogues is indicative of the terminal stages of gastric functional maturation. In this study 6‐to 10‐week‐old human fetal stomachs xenografted into nude mice were used to study parietal cells' functional maturation.

Methods:

Thirty‐four transplants were microsurgically grafted either inside a pouch created on the nude peritoneum (n = 15) or on the host stomach and esophagus (n = 19). The mucosa of transplanted tissues was analyzed by immunohistochemical techniques to detect gastric cells. Gastric cell secretions were collected before and after pentagastrin or omeprazole treatment.

Results:

Parietal, G, and D cells were detected immunohistochemically only after 1 month of grafting. All xenografts actively secreted acid after 1 or 2 months' transplantation at each graft site. Acid secretion was significantly stimulated by intraperitoneally injected pentagastrin (mean pH ± SD, 3.2 ± 0.7 vs. 2.0 ± 0.5;n = 10, P = 0.005) and was dramatically inhibited by intragastrically administered omeprazole (2.3 ± 0.6 vs. 6.5 ± 0.7;n = 15, P = 0.0007) after 5 hours.

Conclusion:

Stomach xenografts were able to develop normally. Parietal cells were physiologically mature with functional proton pumps and active gastrin receptors, as demonstrated after omeprazole and pentagastrin treatment, respectively. Because stomach xenografts matured very rapidly, it is possible that a stomach xenograft model can be used for further studies on the functional maturation of human gastric epithelial cells, as well as the factors that influence this maturation in humans.
Gastric Metaplasia: A Frequently Overlooked Feature of Duodenal Biopsy Specimens in Untreated Celiac Disease
Authors: Shaoul Ronald , Marcon Margaret A. , Okada Yoshio , Cutz Ernest , Forstner Gordon
Published: February 2024

Background:

Duodenal gastric metaplasia is rarely reported in untreated celiac disease, although it is seen in 60% to 100% of duodenal biopsy specimens in nonceliac patients with histologic duodenitis. The low incidence could represent underreporting, a decreased incidence in pediatric patients generally, or the more distal sampling site that is customary for most biopsy specimens that are obtained to diagnose celiac disease. It could also be a unique feature of the inflammatory reaction that characterizes this disease. The purpose of this study was to examine the incidence of gastric metaplasia in duodenal specimens from children with untreated celiac disease with special reference to patient age and biopsy site.

Method:

Formalin‐fixed paraffin‐embedded specimens of duodenal mucosa were selected from the pathology department's archival material. Sections were either stained histochemically or by immunochemical methods, according to an antigen‐retrieval protocol. Forty‐four duodenal specimens from untreated patients with celiac disease (n = 22) and control subjects of similar age with normal histology (n = 22) were examined. Ten of each were obtained during upper endoscopy from the proximal duodenum (proximal site) and 12 of each by Crosby capsule near the ligament of Treitz (distal site).

Results:

All specimens from patients with celiac disease exhibited marked villous atrophy. None had been noted to have gastric metaplasia during routine examination of sections stained by hematoxylin and eosin. Fifteen (68%) of 22 of the celiac specimens and 2 of 22 (9%) control specimens contained gastric metaplasia, identified as patches of gastric‐type cells containing MUC5AC (gastric mucin), pS2 (gastric trefoil factor) and neutral (periodic acid‐Schiff–positive) mucin. Five of the seven celiac specimens that had no metaplasia showed increased numbers of goblet cells expressing gastric markers. The incidence of gastric metaplasia was not different for endoscopic (70%) or capsule (67%) specimens. Sixty‐eight percent (7/11) of patients aged less than 3 years had gastric metaplasia.

Conclusion:

The presence of gastric metaplasia has been previously underreported in celiac disease specimens. Detection would be improved by the routine use of period acid‐Schiff/alcian blue staining. The incidence of gastric metaplasia in celiac disease is not significantly influenced by biopsy site or age at time of the biopsy.
Objective Ranking of Fibrosis in Standard Histologic Sections of Human Neonatal Liver: Applicability to α1‐Antitrypsin Deficiency
Authors: Moustafellos Elaine , Illueca Marta , Remotti Helen E. , Auld Peter A.M. , Hanauske‐Abel Hartmut M.
Published: February 2024

Background

The etiologic heterogeneity of fibrotic liver disease has resulted in the formulation of diverse, often disease‐specific, classification systems for biopsy assessment, based on tissue morphology and staining. Their qualitative nature and observer dependency remain a concern, and no classification exists for several significant conditions—for example, α1‐antitrypsin deficiency (α1‐ATD). The authors propose a disease‐and morphology‐independent numeric ranking system to objectively quantify fibrosis in a standard histologic section, based on its content of protein amino acids. This PNC system is applied to two cases of α1‐ATD liver fibrosis.

Methods

High‐performance liquid chromatography separation of the 6‐aminoquinolyl‐N‐hydroxysuccinimidyl carbamate (AQC)–labeled acid hydrolysate of an individual needle biopsy section, followed by the calculation of specific amino acid ratios to eliminate confounding variables.

Results

As required by the PNC system, three numeric values were identified per tissue section, one increasing (P quotient), one decreasing (N quotient), one constant (C quotient) as fibrosis progresses, assessed by calibration against Knodell‐staged samples. Generated for the α1‐ATD sections, these three coordinates numerically referenced the degree of fibrosis in a manner that in each case was consistent with the histologic evaluation, the laboratory values, and the clinical course.

Conclusions

Numeric, objective referencing of the degree of fibrosis in routine liver biopsy sections, based on the PNC system, is technically possible.
Treatment of Recurrent Abdominal Pain: Components Analysis of Four Treatment Protocols
Authors: Humphreys Patricia A , Gevirtz Richard N
Published: February 2024

Background:

Recurrent abdominal pain (RAP) affects up to 34% of the world's population of children. Medical management has been limited, but behavioral strategies have been shown to be effective. In this study several components of published treatment protocols were adapted and/or improved and then compared using a pretest–posttest control group design.

Methods:

Sixty‐four children and teenagers (mean age, 9.75 ± 2.46 years) with diagnosed recurrent abdominal pain were randomly assigned to four groups: 1) fiber‐only comparison group; 2) fiber and biofeedback‐assisted cultivated low arousal; 3) fiber, biofeedback, and cognitive–behavioral interventions; and 4) fiber, biofeedback, cognitive–behavioral, and parental support. Participants were treated over 8 weeks in individual sessions. Biofeedback was supplied using small thermal devices.

Results:

All groups showed improvement in self‐reported pain, even the fiber‐only comparison group; however, the active treatment groups showed significantly more improvement before and after than the fiber‐only comparison group (fiber only comparison group pain reduction at 79%; fiber and biofeedback at 100%; fiber, biofeedback, and cognitive–behavioral at 94%; fiber, biofeedback, cognitive–behavioral, and parental support at 93%).

Conclusions:

This suggests that any of the active treatment protocols assessed in this investigation work better than established treatments that have been reported in the literature. Because the addition of cognitive and parental support components did not seem to increase treatment effectiveness, it is concluded that increased fiber with biofeedback‐assisted cultivated low arousal was effective and efficient as a treatment modality.
Securing administrative leadership commitment for anticoagulation stewardship programs
Authors: May Jori E. , Triller Darren M. , Inglis Lauren , Rose Anne E. , DiLorenzo‐Agramonte Vicky , Burnett Allison E. , Schumock Glen T. , Kaatz Scott , Barnes Geoffrey D. , Ansell Jack E.
Published: February 2024

Anticoagulation is a leading cause of medication‐related harm. As a result, there is increasing recognition of the importance of the development of anticoagulation stewardship programs to ensure safe and effective anticoagulation use across health care settings. Securing administrative leadership support to build such programs is a necessary first step but is often a significant barrier to implementation. Herein, we present a structured approach to guide providers advocating to leadership for stewardship programs at their institutions. We divide the approach into four phases: (1) Build the foundation, (2) Select stewardship initiatives, (3) Develop implementation plans, and (4) Prepare and present a business plan. Within each phase, we outline specific actions to consider, all leading up to the end goal of creating a compelling business plan to generate administrative leadership buy‐in. We also provide resources to promote the understanding of institutional needs as well as broader trends across health systems that influence stewardship program development. Our aim is to provide stewardship advocates with the tools to effectively secure leadership support to facilitate the development of Anticoagulation Stewardship Programs across all health care institutions.
The coronal alignment differs between two‐dimensional weight‐bearing and three‐dimensional nonweight bearing planning in total knee arthroplasty
Authors: Pflüger Patrick , Hodel Sandro , Zimmermann Stefan M. , Knechtle Svenja , Vlachopoulos Lazaros , Fucentese Sandro F.
Published: February 2024

Purpose

The goal of this study is (1) to assess differences between two‐dimensional (2D) weight‐bearing (WB) and three‐dimensional (3D) nonweight‐bearing (NWB) planning in total knee arthroplasty (TKA) and (2) to identify factors that influence intermodal differences.

Methods

Retrospective single‐centre analysis of patients planned for a TKA with patient‐specific instruments (PSI). Preoperative WB long‐leg radiographs and NWB computed tomography were analysed and following radiographic parameters included: hip–knee–ankle angle (HKA) (+varus/−valgus), joint line convergence angle (JLCA), femorotibial subluxation and bony defect classified according to Anderson. Preoperative range of motion was also considered as possible covariate. Demographic factors included age, sex, and body mass index.

Results

A total of 352 knees of 323 patients (66% females) with a mean age of 66 ± 9.7 years were analysed. The HKA differed significantly between 2D and 3D planning modalities; varus knees (n = 231): 9.9° ± 5.1° vs. 6.7° ± 4°, p < 0.001; valgus knees (n = 121): −8.2° ± 6° vs. −5.5° ± 4.4°, p < 0.001. In varus knees, HKA (β = 0.38; p < 0.0001) and JLCA (β = 0.14; p = 0.03) were associated with increasing difference between 2D/3D HKA. For valgus knees, HKA (β = −0.6; p < 0.0001), JLCA (β = −0.3; p = 0.0001) and lateral distal femoral angle (β = −0.28; p = 0.03) showed a significant influence on the mean absolute difference.

Conclusion

The coronal alignment in preoperative 3D model for PSI‐TKA significantly differed from 2D WB state and the difference between modalities correlated with the extent of varus/valgus deformity. In the vast majority of cases, the 3D NWB approach significantly underestimated the preoperative deformity, which needs to be considered to achieve the planned correction when using PSI in TKA.

Level of Evidence

Level III.
Green titanium dioxide (TiO2) nanoparticles assisted biodegradation of anthracene employing Serratia quinivorans HP5
Authors: Chakravarty Paramita , Deka Hemen , Chowdhury Devasish
Published: February 2024

The anthracene biodegradation potential of Serratia quinivorans HP5 was studied under a controlled laboratory environment. The green TiO2 nanoparticles (NPs) synthesized from Paenibacillus sp. HD1PAH was used to accelerate the biodegradation process. The synergistic application of TiO2 NPs and S. quinivorans HP5 resulted in a reduction of anthracene concentration by 1.2 folds in liquid‐medium and 1.5 folds in contaminated soil. Gas‐chromatography and mass‐spectrometric investigation showed the production of four anthracene derivatives, namely 1,2‐anthracene dihydrodiol, 6,7‐benzocoumarin, anthrone, and 9,10‐anthraquinoneat the termination of experimental periods. Furthermore, bacterial biomass increased by 23.3 folds in the presence of TiO2 NPs, and overall soil enzyme activities were enhanced by 4.2 folds in the treated samples. In addition, there was a negative correlation observed between the biomass of S. quinivorans HP5 and the concentrations of anthracene, suggesting the involvement of bacterium in anthracene biodegradation processes. The degradation pathway of anthracene revealed its transformation into the less toxic compound 9,10‐anthraquinone. Overall, this study elucidates a novel biodegradation pathway for anthracene and highlights the potential of nano‐assisted bacterial remediation as a promising approach for environmental cleanup.
Climate change signals of extreme precipitation return levels for Germany in a transient convection‐permitting simulation ensemble
Authors: Hundhausen Marie , Feldmann Hendrik , Kohlhepp Regina , Pinto Joaquim G.
Published: February 2024

The increase in extreme precipitation with global warming (GW) and associated uncertainties are major challenges for climate adaptation. To project future extreme precipitation on different time and intensity scales (return periods [RPs] from 1 to 100 a and durations from 1 h to 3 days), we use a novel convection‐permitting (CP), multi‐global climate model ensemble of COSMO‐CLM regional simulations with a transient projection time (1971–2100) over Germany. We find an added value of the CP scale (2.8 km) with respect to the representation of hourly extreme precipitation intensities compared to the coarser scale with parametrized deep convection (7 km). In general, the return levels (RLs) calculated from the CP simulations are in better agreement with those of the conventional observation‐based risk products for the region for short event durations than for longer durations, where an overestimation by the simulation‐based results was found. A maximum climate change signal of 6–8.5% increase per degree of GW is projected within the CP ensemble, with the largest changes expected for short durations and long RPs. Analysis of the uncertainty in the climate change signal shows a substantial residual standard deviation of a linear approximation, highlighting the need for transient data sets instead of time‐slice experiments to increase confidence in the estimates. Furthermore, the ensemble spread is found to be smallest for intensities of short duration, where changes are expected to be based mainly on thermodynamic contributions. The ensemble spread is larger for long, multi‐day durations, where a stronger dependence on the dynamical component is ascribed. In addition, an increase in spatial variance of the RLs with GW implies a more variable future climate and points to an increasing importance of accounting for uncertainties.
Patient Sex Mediates the Influence of Patient Age on Superior Canal Dehiscence Repair Outcome
Authors: Yang Hong‐Ho , Yang Isaac , Gopen Quinton S.
Published: February 2024

Objective

To investigate the independent and interactive effects of patient age and sex on superior canal dehiscence (SCD) repair outcomes.

Methods

This was a cohort study of consecutive SCD repairs via the middle fossa approach at an institution between 2011 and 2022. We constructed multivariable regression models assessing surgical outcomes with age and sex as the primary predictors. Models controlled for surgery duration, follow‐up duration, and relevant surgical and medical history. Subsequently, we repeated each model with the incorporation of an interaction term between patient age and sex.

Results

Among 402 repairs, average age was 50 years, and 63% of cases were females. There was a significant interaction between patient age and sex with respect to symptom resolution score (SRS) (adj. β 0.80, 95% C.I. 0.04–1.56). Older age was associated with lower SRS among females (−0.84, −1.29 to −0.39 point per year) but not significantly associated with SRS among males (0.04, −0.65 to 0.56 point per year). Furthermore, older age independently predicted a greater magnitude of increase in air conduction at 8000 Hz following surgery regardless of sex (adj. β 2.1, 0.2–4.0 dB per 10‐year increase).

Conclusions

This is the first study on the interactive effect between patient age and sex with respect to SCD repair outcomes. Older age predicted poorer symptomatic response among female patients but did not predict symptomatic response among male patients. Furthermore, older age predicted more severe high‐frequency hearing loss following SCD repairs among both female and male patients.

Level of Evidence

3 Laryngoscope, 134:3363–3370, 2024