bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTBackground: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

ABSTRACTBackground: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

ABSTRACTBackground: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

ABSTRACTBackground: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

ABSTRACTThe 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

ABSTRACTBackground: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

ABSTRACTBackground: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

ABSTRACTBackgroundThe 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.MethodsHigh‐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.ResultsAs 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.ConclusionsNumeric, 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

ABSTRACTBackground: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

AbstractAnticoagulation 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

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

AbstractThe 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.