Jewish Hospital

About: Jewish Hospital is a healthcare organization based out in Cincinnati, Ohio, United States. It is known for research contribution in the topics: Antigen & Population. The organization has 3881 authors who have published 3414 publications receiving 123044 citations.

Studies of tumor hypoglycemia

Abstract: Fasting hypoglycemia, in a patient with an intrathoracic mesothelioma, was corrected by surgical excision of the tumor. Studies of the patient and the tumor revealed the following: Asymptomatic hypoglycemia, reversible with exogenous glucagon, evolved slowly and only after several hours of fasting; plasma immunoreactive insulin (IRI) response to provocative testing improved after excision of the tumor; circulating insulin-like activity (ILA), as measured by three bioassays (rat epididymal fat pad, rat hemi-diaphragm, and the in vivo method of Rafaelson 20 ), correlated very well with IRI, and both were appropriate; the tumor had a high rate of glucose uptake, glucose metabolism predominantly being by anaerobic glycolysis and unresponsive to insulin, and extracted no free fatty acids (FFA); trace amounts only of ILA or IRI were present in tumor homogenates. The patient's endocrine counter-regulatory mechanisms were not activated despite fasting hypoglycemia, for plasma growth hormone, cortisol and FFA levels were no higher before surgery (when hypoglycemic) than after (when normoglycemic). Acute hypoglycemia, during an insulin tolerance test, promptly elicited appropriate endocrine responses. Parallels between this form of hypoglycemia, and that associated with glucagon deficiency, suggest that two additional factors may operate in patients with tumor-associated hypoglycemia: Rates of plasma glucose decline less than critical may fail to trigger counter-regulatory endocrine responses until profound hypoglycemia develops; an acquired form of glucagon deficiency may impair glucose counter-regulatory processes.

ALS blood expression profiling identifies new biomarkers, patient subgroups, and evidence for neutrophilia and hypoxia

Abstract: Amyotrophic lateral sclerosis (ALS) is a debilitating disease with few treatment options. Progress towards new therapies requires validated disease biomarkers, but there is no consensus on which fluid-based measures are most informative. This study analyzed microarray data derived from blood samples of patients with ALS (n = 396), ALS mimic diseases (n = 75), and healthy controls (n = 645). Goals were to provide in-depth analysis of differentially expressed genes (DEGs), characterize patient-to-patient heterogeneity, and identify candidate biomarkers. We identified 752 ALS-increased and 764 ALS-decreased DEGs (FDR 10% expression change). Gene expression shifts in ALS blood broadly resembled acute high altitude stress responses. ALS-increased DEGs had high exosome expression, were neutrophil-specific, associated with translation, and overlapped significantly with genes near ALS susceptibility loci (e.g., IFRD1, TBK1, CREB5). ALS-decreased DEGs, in contrast, had low exosome expression, were erythroid lineage-specific, and associated with anemia and blood disorders. Genes encoding neurofilament proteins (NEFH, NEFL) had poor diagnostic accuracy (50–53%). However, support vector machines distinguished ALS patients from ALS mimics and controls with 87% accuracy (sensitivity: 86%, specificity: 87%). Expression profiles were heterogeneous among patients and we identified two subgroups: (i) patients with higher expression of IL6R and myeloid lineage-specific genes and (ii) patients with higher expression of IL23A and lymphoid-specific genes. The gene encoding copper chaperone for superoxide dismutase (CCS) was most strongly associated with survival (HR = 0.77; P = 1.84e−05) and other survival-associated genes were linked to mitochondrial respiration. We identify a 61 gene signature that significantly improves survival prediction when added to Cox proportional hazard models with baseline clinical data (i.e., age at onset, site of onset and sex). Predicted median survival differed 2-fold between patients with favorable and risk-associated gene expression signatures. Peripheral blood analysis informs our understanding of ALS disease mechanisms and genetic association signals. Our findings are consistent with low-grade neutrophilia and hypoxia as ALS phenotypes, with heterogeneity among patients partly driven by differences in myeloid and lymphoid cell abundance. Biomarkers identified in this study require further validation but may provide new tools for research and clinical practice.

Inter-relationships between bone mineral content measures. Dual energy radiography (DER) and bitewing radiographs (BWX).

Abstract: In vitro periodontal alveolar bone mineral content (BMC) measurements obtained with dual-energy radiography (DER) were compared with assessments based on bitewing radiographs (BWX). In addition, in patients, the relationship between bitewing and several postcranial dual-energy-radiographic measures were evaluated. Dual-energy-radiographic and bitewing measurements were made on 2 cadaver mandibles initially and after 2 incremental bone reductions at 4 sites. Rank-order correlations between dual-energy-radiographic and bitewing measures for the 4 sites ranged from 0.7 to 1.00. Bitewing measures indicated true bone loss with a sensitivity of 1.00. For patients, correlations between bitewing measures and dual-energy-radiographic scans suggested the strongest relationships were in the distal sections of the radius and ulna and in the intertrochanteric and Ward's areas of the femur. Correlations, in the 0.5-0.6 range, were not statistically significant (p > 0.05), but were quite robust considering the small sample size and preliminary nature of this investigation. Results suggest that the bitewing measure is sufficiently sensitive to detect clinically meaningful (5% or greater) changes in alveolar BMC and, further, that alveolar bone mineral content may reflect postcranial BMC. The implications of postcranial bone mineral changes being reflected in alveolar bone would enhance both our understanding and treatment of alveolar bone loss. The use of bitewing measures to facilitate identification of patients with postcranial bone loss is discussed.