Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells

Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.     

Supernumerary right coronary artery

A rare case of a patient with supernumerary right coronary artery in whom the two vessels arose from the right coronary sinus from two separate ostia adjacent to each other is presented. The smaller vessel gave off the sinoatrial nodal branch and the posterior descending artery whereas the larger one gave off the conus branch, the right ventricular branches, and continued as acute marginal branch. This is the first case report in the English literature.     

Relationship of quality of life and physical function measures with disease activity in children with systemic lupus erythematosus

The objective of this study is to assess relationship of systemic lupus erythematosus (SLE) activity with quality of life (QOL) and physical function and determine which is more closely correlated with SLE activity in children; and identify factors critical to children's QOL. In this cross-sectional study, children with SLE and parents completed corresponding versions of physical function (Childhood Health Assessment Questionnaire CHAQ), and QOL (Pediatric Quality of Life Inventory-PedsQL Generic/Rheumatology modules) questionnaires. SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), severity, self-concept and socioeconomic status (SES) were measured. For 24 children, CHAQ scores significantly correlated with SLEDAI (rho = 0.4, p = 0.04), SDI (rho = 0.6, p = 0.004), and associated with severity (p = 0.03). PedsQL scores did not significantly correlate with above parameters. Higher self-concept/SES correlated (p < 0.05) with better physical function and QOL. For 19 parents, the only significant correlation was between SLEDAI and Worry domain-Rheumatology module (rho = 0.5, p = 0.01). Lack of strong correlation of disease activity with QOL and physical function suggests that they are different constructs with partial overlap, and should be considered collectively while evaluating the impact of SLE on children/families. Self-concept and SES should be assessed while measuring QOL in children. Larger sample is required to confirm results.     

The Effect of Standard Versus Longer Intestinal Bypass on GLP-1 Regulation and Glucose Metabolism in Patients With Type 2 Diabetes Undergoing Roux-en-Y Gastric Bypass: The Long-Limb Study

OBJECTIVERoux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.RESEARCH DESIGN AND METHODSA total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery.RESULTSBoth groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity.CONCLUSIONSThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.