Find early markers for Necrosis and additional Cholestasis and negative controls
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ABSTRACT:
ORGANISM(S): Mus musculus
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PROVIDER: S-DIXA-090 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description: Not available
| S-DIXA-088 | biostudies-other
Project description:To describe primary care management of early and prolonged jaundice in otherwise-healthy term infants to identify opportunities to increase early diagnosis of cholestasis.Community-based pediatricians in St Louis, Missouri completed a mailed, anonymous, 29-item survey to assess practice demographics, timing of routine newborn office visits, and the management of early and prolonged neonatal jaundice.A total of 108 of 230 (47%) of eligible physicians responded (mean years in practice, 15.3, SD, 9.4). More respondents were very familiar with national guidelines for management of early (49%) than prolonged (16%) neonatal jaundice. Eighty-six percent reported all newborns were checked with transcutaneous bilirubin before hospital discharge. For transcutaneous bilirubin results at 48 hours of 7, 10, 12 and 15 mg/dL, 1%, 26%, 70%, and 74% of respondents, respectively, would order a fractionated bilirubin. Although the first routine visit usually occurred in the first week after discharge, 25% of physicians reported the 2nd visit was routinely scheduled after 4 weeks of age. Ninety-four percent reported they would obtain a fractionated bilirubin for infants jaundiced beyond 4 weeks of age. If cholestasis was identified at 6 weeks of age, 32% would obtain additional testing without referral to a subspecialist.Management of early and prolonged neonatal jaundice is variable. Current practices appear to miss opportunities for early diagnosis of cholestasis and referral that are unlikely to be addressed without redesigning systems of care.
| S-EPMC3398230 | biostudies-literature
Project description:BackgroundCurrent guidelines recommend viral, autoimmune, coagulation and liver ultrasound testing in intrahepatic cholestasis of pregnancy to exclude alternative diagnoses.MethodsElectronic health records were searched for investigations and diagnoses in women with raised bile acid concentrations (>10 µmol/L) between January 2016 and December 2017 at two UK maternity units.ResultsFive hundred and thirty-one women had a raised bile acid concentration (median (IQR): 18 (13-32 µmol/L)) at a median gestation of 35.1 (IQR 31.8-37.0) weeks. Out of 531 women, 250 (47.1%) had full virology, autoimmune and ultrasound tests, and 348 (65.5%) had coagulation performed. Positive hepatitis B and C results were previously known. No new Epstein-Barr virus, cytomegalovirus or hepatitis A diagnoses were made. There were 11 positive autoimmune results, but no new diagnoses. No woman had an unexplained prolonged prothrombin time. No ultrasound liver (n = 38) or gallbladder (n = 85) abnormalities were of acute clinical significance.ConclusionIntrahepatic cholestasis of pregnancy investigations provided no new diagnoses that influenced clinical management during pregnancy.
| S-EPMC7726172 | biostudies-literature
Project description:Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models.
| S-EPMC4361327 | biostudies-literature
Project description:Testing of symptomatic persons for infection with severe acute respiratory syndrome coronavirus-2 is occurring worldwide. We propose two types of case-control studies that can be carried out jointly in test settings for symptomatic persons. The first, the test-negative case-control design (TND) is the easiest to implement; it only requires collecting information about potential risk factors for Coronavirus Disease 2019 (COVID-19) from the tested symptomatic persons. The second, standard case-control studies with population controls, requires the collection of data on one or more population controls for each person who is tested in the test facilities, so that test-positives and test-negatives can each be compared with population controls. The TND will detect differences in risk factors between symptomatic persons who have COVID-19 (test-positives) and those who have other respiratory infections (test-negatives). However, risk factors with effect sizes of equal magnitude for both COVID-19 and other respiratory infections will not be identified by the TND. Therefore, we discuss how to add population controls to compare with the test-positives and the test-negatives, yielding two additional case-control studies. We describe two options for population control groups: one composed of accompanying persons to the test facilities, the other drawn from existing country-wide healthcare databases. We also describe other possibilities for population controls. Combining the TND with population controls yields a triangulation approach that distinguishes between exposures that are risk factors for both COVID-19 and other respiratory infections, and exposures that are risk factors for just COVID-19. This combined design can be applied to future epidemics, but also to study causes of nonepidemic disease.
| S-EPMC7523580 | biostudies-literature
Project description:Biliary atresia (BA) is the most serious liver disease in infants. Diagnosis currently depends on surgical exploration of the biliary tree. Noninvasive tests that distinguish BA from other types of neonatal liver disease are not available.To identify potential serum biomarkers that classify children with neonatal cholestasis, we performed 2-dimensional difference gel electrophoresis, statistical analysis, and tandem mass spectrometry using serum samples from 19 infants with BA and 19 infants with non-BA neonatal cholestasis.Eleven potential serum biomarkers were found that could in combination classify children with neonatal cholestasis.Although no single biomarker or imaging test adequately distinguishes BA from other types of neonatal cholestasis, combinations of biomarkers, imaging tests, and noninvasive clinical criteria should be further explored as potential tests for rapid and accurate diagnosis of BA.
| S-EPMC2881691 | biostudies-literature
Project description:Introduction. The question of whether a single day of incubation is sufficient for urine cultures has been a matter of debate.Aim. The aim of this study was to investigate the potential benefit of prolonged incubation for initially culture-negative urines.Methodology. Eight hundred and twelve urine specimens with no growth after incubation for 20 h were incubated for an additional 20 h to detect slower growing uropathogenic organisms.Results. This study included a considerable number of urine cultures from immunocompromised and/or kidney-transplanted patients. For 99.9 % of the specimens, there was no difference in the interpretation of results.Conclusion. Twenty hours of incubation did not have any negative effect on the detection of uropathogens.
| S-EPMC7440675 | biostudies-literature
Project description:BACKGROUND: Despite the impressive growth of sequence databases, the limited availability of nuclear markers that are sufficiently polymorphic for population genetics and phylogeography and applicable across various phyla restricts many potential studies, particularly in non-model organisms. Numerous introns have invariant positions among kingdoms, providing a potential source for such markers. Unfortunately, most of the few known EPIC (Exon Primed Intron Crossing) loci are restricted to vertebrates or belong to multigenic families. RESULTS: In order to develop markers with broad applicability, we designed a bioinformatic approach aimed at avoiding multigenic families while identifying intron positions conserved across metazoan phyla. We developed a program facilitating the identification of EPIC loci which allowed slight variation in intron position. From the Homolens databases we selected 29 gene families which contained 52 promising introns for which we designed 93 primer pairs. PCR tests were performed on several ascidians, echinoderms, bivalves and cnidarians. On average, 24 different introns per genus were amplified in bilaterians. Remarkably, five of the introns successfully amplified in all of the metazoan genera tested (a dozen genera, including cnidarians). The influence of several factors on amplification success was investigated. Success rate was not related to the phylogenetic relatedness of a taxon to the groups that most influenced primer design, showing that these EPIC markers are extremely conserved in animals. CONCLUSIONS: Our new method now makes it possible to (i) rapidly isolate a set of EPIC markers for any phylum, even outside the animal kingdom, and thus, (ii) compare genetic diversity at potentially homologous polymorphic loci between divergent taxa.
| S-EPMC2949868 | biostudies-literature
Project description:microRNA array profiling by comparing the isolated cholangiocytes from Bile Duct Ligated and Normal mouse liver
2014-12-31 | E-MTAB-2267 | biostudies-arrayexpress