ABSTRACT
Synthetic patch materials currently in use have major limitations, such as high susceptibility to infections and lack of contractility. Biological grafts are a novel approach to overcome these limitations, but do not always offer sufficient mechanical durability in early stages after implantation. Therefore, a stabilising structure based on resorbable magnesium alloys could support the biological graft until its physiologic remodelling. To prevent early breakage in vivo due to stress of non-determined forming, these scaffolds should be preformed according to the geometry of the targeted myocardial region. Thus, the left ventricular geometry of 28 patients was assessed via standard cardiac magnetic resonance imaging (MRI). The resulting data served as a basis for a finite element simulation (FEM). Calculated stresses and strains of flat and preformed scaffolds were evaluated. Afterwards, the structures were manufactured by abrasive waterjet cutting and preformed according to the MRI data. Finally, the mechanical durability of the preformed and flat structures was compared in an in vitro test rig. The FEM predicted higher durability of the preformed scaffolds, which was proven in the in vitro test. In conclusion, preformed scaffolds provide extended durability and will facilitate more widespread use of regenerative biological grafts for surgical left ventricular reconstruction.
Subject(s)
Absorbable Implants , Alloys/chemical synthesis , Guided Tissue Regeneration/instrumentation , Heart Ventricles/anatomy & histology , Heart-Assist Devices , Magnesium Compounds/chemical synthesis , Tissue Scaffolds , Adult , Computer Simulation , Computer-Aided Design , Equipment Failure Analysis , Female , Humans , Male , Models, Anatomic , Models, Cardiovascular , Prosthesis Design , Prosthesis Fitting/methodsABSTRACT
Platelet factor 4 (PF-4) is an archetype of the "chemokine" family of low molecular weight proteins that play an important role in injury responses and inflammation. From activated human leukocyte culture supernatants, we have isolated a form of PF-4 that acts as a potent inhibitor of endothelial cell proliferation. The PF-4 derivative is generated by peptide bond cleavage between Thr-16 and Ser-17, a site located downstream from the highly conserved and structurally important CXC motif. The unique cleavage leads to a loss of one of the structurally important large loops in the PF-4 molecule and generation of an N terminus with basic residues that have the potential to interact with the acidic extracellular domain of the G-protein-coupled chemokine receptor. The N-terminal processed PF-4 exhibited a 30- to 50-fold greater growth inhibitory activity on endothelial cells than PF-4. Since endothelial cell growth inhibition is the only known cellular activity of the cleaved PF-4, we have designated this chemokine endothelial cell growth inhibitor. The N-terminal processing of PF-4 may represent an important mechanism for modulating PF-4 activity on endothelial cells during tissue injury, inflammation, and neoplasia.
Subject(s)
Endothelium, Vascular/cytology , Growth Inhibitors/pharmacology , Leukocytes/physiology , Platelet Factor 4/pharmacology , Amino Acid Sequence , Animals , Aorta , Cattle , Cells, Cultured , Culture Media, Conditioned , DNA/biosynthesis , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Fetus , Growth Inhibitors/chemistry , Heart , Humans , Kinetics , Models, Structural , Molecular Sequence Data , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Platelet Factor 4/chemistry , Platelet Factor 4/metabolism , Protein Structure, Secondary , Serine , ThreonineABSTRACT
A 39-month clinical study of leptospirosis was undertaken at the Queen Elizabeth Hospital, Barbados, Eighty-eight patients had a confirmed diagnosis of the disease during the period. The major serogroups identified were autumnalis (including a new serovar bim), icterohaemorrhagiae, ballum and canicola. The majority of patients presented with jaundice (95%,) anorexia and headaches (85%), fever (76%) and conjunctival suffusion (54%). While abnormal creatinine levels were seen in 49% of patients on admission, only 16% were judged to have had renal failure. The urine to plasma urea ratio showed high sensitivity and specificity in the diagnosis of pre-renal azotemia. Cardiac arrhythmias and myocarditis occurred in 18% of patients and pericarditis in 6%. An elevated serum amylase was found in 65% of cases. The bilirubin level took 5.5 weeks to return to normal. Thrombocytopenia was shown not to be due to a disseminated intravascular coagulation, and a randomised trial of high dose penicillin did not reveal any benefit to jaundiced patients. The overall mortality during the study was 5.7%
Subject(s)
Humans , Adolescent , Adult , Middle Aged , Male , Female , Leptospira interrogans serovar canicola/classification , Leptospira interrogans/classification , Leptospirosis/epidemiology , Barbados/epidemiology , Leptospirosis/complications , Leptospirosis/diagnosis , SerotypingABSTRACT
The cytogenetic effects of phenytoin (PHT) and/or carbamazepine (CBZ) were studied to determine clastogenic potential. Comparative analysis of chromosome breakage and sister chromatid exchange (SCE) was performed between 18 patients with epilepsy receiving PHT and/or CBZ and 10 healthy nontreated controls. These studies failed to detect a significant increase in chromosome aberrations or SCEs in groups of treated individuals as compared with controls. No correlation was observed between the rate of either chromosome damage or SCEs and age, sex, drug blood level, or daily dose. The results indicate no detectable chromosome damaging effects of PHT alone, CBZ alone, or a combination of these two antiepileptic drugs (AEDs).
