Glucagon secretion in acute and chronic pancreatitis.

Plasma pancreatic glucagon concentrations were determined in the basal state and after the infusion of alanine in 10 patients with acute pancreatitis (5 in an initial episode of pancreatitis), in 10 patients with chronic pancreatic insufficiency, and in 21 healthy controls. In acute pancreatitis, basal glucagon levels were nine times normal but were higher during the initial attack than with a history of previous attacks. The glucagon response to alanine was also increased threefold to fourfold in initial attacks. In contrast, after recovery from the initial attack of acute pancreatitis, during acute episodes of pancreatitis in patients with a history of previous attacks, and in patients with pancreatic insufficiency, alanine failed to elicit a consistent rise in plasma glucagon. The data suggest that hyperglucagonemia may contribute to the hyperglycemia of acute pancreatitis, particularly during the initial episode. Loss of alpha cell responsiveness to alanine provides a sensitive index of previous pancreatitis.     

Associations between model-predicted rivaroxaban exposure and patient characteristics and efficacy and safety outcomes in the treatment of venous thromboembolism

Journal of Thrombosis and Thrombolysis - Traditional statistical models allow population based inferences and comparisons. Machine learning (ML) explores datasets to develop algorithms that do not...     

Lead Exposure,B Vitamins,and Plasma Homocysteine in Men 55 Years of Age and Older: The VA Normative Aging Study

Background: Lead (Pb) exposure may influence the plasma concentration of homocysteine, a one-carbon metabolite associated with cardiovascular and neurodegenerative diseases. Little is known about the associations between Pb and homocysteine over time, or the potential influence of dietary factors.Objectives: We examined the longitudinal association of recent and cumulative Pb exposure with homocysteine concentrations and the potential modifying effect of dietary nutrients involved in one-carbon metabolism.Methods: In a subcohort of the Veterans Affairs (VA) Normative Aging Study (1,056 men with 2,301 total observations between 1993 and 2011), we used mixed-effects models to estimate differences in repeated measures of total plasma homocysteine across concentrations of Pb in blood and tibia bone, assessing recent and cumulative Pb exposure, respectively. We also assessed effect modification by dietary intake and plasma concentrations of folate, vitamin B₆, and vitamin B₁₂.Results: An interquartile range (IQR) increment in blood Pb (3 μg/dL) was associated with a 6.3% higher homocysteine concentration (95% CI: 4.8, 7.8%). An IQR increment in tibia bone Pb (14 μg/g) was associated with a 3.7% higher homocysteine (95% CI: 1.6, 5.6%), which was attenuated to 1.5% (95% CI: –0.5, 3.6%) after adjusting for blood Pb. For comparison, a 5-year increase in time from baseline was associated with a 5.7% increase in homocysteine (95% CI: 4.3, 7.1%). The association between blood Pb and homocysteine was significantly stronger among participants with estimated dietary intakes of vitamin B₆ and folate below (vs. above) the study population medians, which were similar to the U.S. recommended dietary allowance intakes.Conclusions: Pb exposure was positively associated with plasma homocysteine concentration. This association was stronger among men with below-median dietary intakes of vitamins B₆ and folate. These findings suggest that increasing intake of folate and B₆ might reduce Pb-associated increases in homocysteine, a risk factor for cardiovascular disease and neurodegeneration.Citation: Bakulski KM, Park SK, Weisskopf MG, Tucker KL, Sparrow D, Spiro A III, Vokonas PS, Nie LH, Hu H, Weuve J. 2014. Lead exposure, B vitamins, and plasma homocysteine in men 55 years of age and older: the VA Normative Aging Study. Environ Health Perspect 122:1066–1074; http://dx.doi.org/10.1289/ehp.1306931     

Additional clinical value of voxel‐based morphometric MRI post‐processing for MRI‐negative epilepsies: a prospective study

Aims: Magnetic resonance imaging is of paramount importance in the presurgical evaluation of drug resistant epilepsy. Detection of a potentially epileptogenic lesion significantly improves seizure outcome after surgery. To optimize the detection of subtle lesions, MRI post‐processing techniques may be of essential help. Methods: In this study, we aimed to evaluate the detection rate of the voxel‐based morphometric analysis program (MAP) in a prospective trial. We aimed to study the MAP+ findings in terms of their clinical value in the decision‐making process of the presurgical evaluation. Results: We included, prospectively, 21 patients who had negative MRI by visual analysis. In a first step, results of the conventional non‐invasive presurgical evaluation were discussed, blinded to the MAP results, in multidisciplinary patient management conferences to determine the possible seizure onset zone and to set surgical or invasive evaluation plans. Thereafter, MAP results were presented, and the change of initial clinical plan was recorded. All MAP detections were reaffirmed by a neuroradiologist with epilepsy expertise. For the 21 patients included, mean age at the time of patient management conference was 26 years (SD 15 +/‐ years, range: 5–54 years). In total, 4/21 had temporal lobe epilepsy and 17/21 had extra‐temporal lobe epilepsy. MAP was positive in 10/21 (47%) patients and in 6/10 (60%) a diagnosis of focal cortical dysplasia was confirmed after neuroradiologist review, corresponding to a 28% detection rate. MAP+ findings had a clear impact on the initial management in 7/10 patients (7/21, 33% of all patients), which included an adaptation of the intracranial EEG plan (6/7 patients), or the decision to proceed directly to surgery (1/7 patients). Conclusion: MRI post‐processing using the MAP method yielded an increased detection rate of 28% for subtle dysplastic lesions in a prospective cohort of MRI‐negative patients, indicating its potential value in epilepsy presurgical evaluation.     

Über Konstitutionelle Eosinophilie bei chronischen Arthritiden

Ohne Zusammenfassung     

Über Flüssigkeitsstruktur

Ohne Zusammenfassung     

Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Intra-genotypic diversity of archival G4P[8] human rotaviruses from Washington, DC

Group A human rotaviruses (RVs) remain the most frequently detected viral agents associated with acute gastroenteritis in infants and young children. Despite their medical importance, relatively few complete genome sequences have been determined for commonly circulating G/P-type strains (i.e., G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]). In the current study, we sequenced the genomes of 11 G4P[8] isolates from stool specimens that were collected in Washington, DC during the years of 1974–1991. We found that the VP7–VP4–VP6–VP1–VP2–VP3–NSP1–NSP2–NSP3–NSP4–NSP5/6-encoding genes of all 11 G4P[8] RVs have the genotypes of G4-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. By constructing phylogenetic trees for each gene, extensive intra-genotypic diversity was revealed among the G4P[8] RVs, and new sub-genotype gene alleles were identified. Several of these alleles are nearly identical to those of G3P[8] isolates previously sequenced from this same Washington, DC collection, strongly suggesting that the RVs underwent gene reassortment. On the other hand, we observed that some G4P[8] RVs exhibit completely different allele-based genome constellations, despite being collected during the same epidemic season; there was no evidence of gene reassortment between these strains. This observation extends our previous findings and supports the notion that stable, genetically-distinct clades of human RVs with the same G/P-type can co-circulate in a community. Interestingly, the sub-genotype gene alleles found in some of the DC RVs share a close evolutionary relationship with genes of more contemporary human strains. Thus, archival human RVs sequenced in this study might represent evolutionary precursors to modern-day strains.