Therapeutic Angiogenesis With Basic Fibroblast Growth Factor: Technique and Early Results

Background. Patients not amenable to complete myocardial revascularization by conventional methods present a difficult clinical problem. Here we present the early results and technical considerations of the administration of basic fibroblast growth factor for the induction of collateral growth using heparin-alginate slow-release devices in patients undergoing coronary artery bypass grafting.

Methods. Eight patients were enrolled. Patients were candidates if they had at least one graftable obstructed coronary artery and at least one major arterial distribution not amenable to revascularization, a serum creatinine level less than 3 mg/dL, ejection fraction greater than 0.20, and estimated operative mortality of less than 25%. During conventional coronary artery bypass grafting, 10 heparin-alginate devices, each containing either 1 μg or 10 μg of basic fibroblast growth factor, were implanted in the epicardial fat in multiple regions of the unrevascularizable territory and also in the distal distribution of a grafted or patent artery.

Results. There was no mortality and no evidence of renal, hematologic, or hepatic toxicity during follow-up. Three months after the operation, all patients remain free of angina. Seven patients were examined with stress perfusion scans. Three patients had clear enhancement of perfusion to the unrevascularized myocardium, 1 patient had a new fixed defect, and 3 had minimal overall change but had evidence of new small, fixed perfusion defects. Seven patients had improved or similar myocardial contractile function (ejection fraction at 3-month follow-up = 0.53 ± 0.22 versus 0.47 ± 0.14 preoperatively). One patient suffered a perioperative myocardial infarction in the area of basic fibroblast growth factor administration.

Conclusions. This preliminary study demonstrates the safety and technical feasibility of therapeutic angiogenesis with basic fibroblast growth factor delivered by heparin-alginate slow-release devices. Further studies examining the safety, clinical efficacy, and long-term results are ongoing.     

Pericardial Effusions in Adolescent Girls With Anorexia Nervosa: Clinical Course and Risk Factors

The aim of this study was to evaluate cardiac, biochemical and endocrine differences between female adolescents with anorexia nervosa (AN) with and without pericardial effusions. We studied 128 female adolescents (9.8–17.7 years) with anorexia nervosa (AN) diagnosed according to DSM-IV (American Psychiatric Association, 1994 American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th, Washington, DC: Author.  [Google Scholar]) criteria. They all underwent an echocardiographic evaluation. In 29 patients (22.2 %) a pericardial effusion (ranging between ≥ 0.35–2.5 cm) was noted. None of the patients were clinically symptomatic. After 3 months of refeeding, the effusions disappeared in 18/29 patients while in 7/29 patients a pericardial effusion > 0.3 cm persisted. Risk factors for development of effusions were a BMI ≤ 13,5 kg/m², weight loss ≥ 25% and IGF-1-level ≤100 ng/ml. Pericardial effusions are common in adolescent AN patients. They are mostly asymptomatic not requiring any intervention and spontaneously regress with refeeding. They are more common in the patients with the most significant weight loss.     

Allgemeine Therapie

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Syndecan-4 clustering induces cell migration in a PDZ-dependent manner

Cell migration is a dynamic process involving formation of a leading edge in the direction of migration and adhesion points from which tension is generated to move the cell body forward. At the same time, disassembly of adhesion points occurs at the back of the cell, a region known as the trailing edge. Syndecan-4 (S4) is a transmembrane proteoglycan thought to be involved in the formation of focal adhesions. Recent studies have shown that its cytoplasmic domain can engage in signal transduction, making S4 a bona fide receptor. Here, we show that ligand clustering of cell surface S4 on endothelial cells initiates a signaling cascade that results in activation of Rac1, induction of cell polarization, and stimulation of cell migration that depends on S4 interaction with its PDZ-binding partner. Expression of an S4 mutant lacking its PDZ-binding region (S4-PDZ(-)) leads to decreased cell motility and a failure to form a trailing edge. On clustering S4, but not S4-PDZ(-), targets activated Rac1 to the leading edge of live cells. Cells lacking synectin, a PDZ domain containing protein that interacts with S4, fail to migrate in response to S4 clustering. Both S4-PDZ(-)-expressing and synectin(-/-) endothelial cells exhibit elevated basal levels of Rac1. Thus, our data suggest that S4 promotes endothelial cell migration in response to ligand binding by activating Rac1 and localizing it to the leading edge, and that these processes are dependent on its PDZ-binding domain interaction with synectin.     

On the ERN and the significance of errors

The error-related negativity (ERN) is an event-related brain potential observed when subjects commit errors. To examine whether the ERN is sensitive to the value of errors, the motivational significance of errors was manipulated in two experiments. In Experiment 1, low and high monetary value errors were compared to evaluate the effect of trial value on the ERN. In Experiment 2, subjects performed a flanker task both while their performance was being evaluated and during a control condition. Consistent with the notion that the error-detection system is sensitive to the significance of errors, the ERN was significantly larger on high-value trials in Experiment 1 and during evaluation in Experiment 2. There were no corresponding effects on the correct response negativity, and no behavioral differences between conditions were evident in either experiment. These results are discussed in terms of the functional role of the ERN in response monitoring.     

Sequence and genomic organization of GBV-C: A novel member of the flaviviridae associated with human non-A-E hepatitis

Recently, sequences from a novel virus, termed GB virus C (GBV-C), were identified in serum from several patients with cryptogenic hepatitis. In the present study, the nucleotide sequence of this virus has been extended to near-genome length. GBV-C encodes a putative single large polyprotein in which the structural proteins are positioned at the N-terminal end, with the nonstructural proteins located at the C-terminal end. Amino acid sequence analysis of this large polyprotein reveals the presence of protease, helicase, and replicase motifs. Sequence alignments of the polyprotein followed by phylogenetic analyses suggest that GBV-C is a member of the Flaviviridae, most closely related to the recently described GB virus A. © 1996 Wiley-Liss, Inc.     

High-resolution computed tomography study of the cranium of a fossil anthropoid primate, Parapithecus grangeri: new insights into the evolutionary history of primate sensory systems

Extant anthropoids have large brains, small olfactory bulbs, and high-acuity vision compared with other primates. The relative timing of the evolution of these characteristics may have important implications for brain evolution. Here computed tomography is used to examine the cranium of a fossil anthropoid, Parapithecus grangeri. It is found that P. grangeri had a relatively small brain compared with living primates. In addition, it had an olfactory bulb in the middle of the range for living primates. Methods for relating optic foramen area and other cranial measurements to acuity are discussed. Multiple regression is used to estimate retinal ganglion cell number in P. grangeri. Given currently available comparative data, P. grangeri seems to have had retinal ganglion cell counts intermediate for living primates, overlapping with the upper end of the range for strepsirrhines and possibly with the lower end for anthropoids.