ABSTRACT
BACKGROUND: Liver resection is associated with a high proportion of red blood cell transfusions. There is a proposed association between perioperative transfusions and increased risk of complications and tumor recurrence. This study reviews the evidence of this association in the literature. METHODS: The Medline, EMBASE, and Cochrane databases were searched for clinical trials or observational studies of patients undergoing liver resection that compared patients who did and did not receive a perioperative red blood cell transfusion. Outcomes were mortality, complications, and cancer survival. RESULTS: Twenty-two studies involving 6832 patients were included. All studies were retrospective, with no clinical trials. No studies were scored as low risk of bias. The overall proportion of patients transfused was 38.3%. After multivariate analysis, 1 of 5 studies demonstrated an association between transfusion and increased mortality; 5 of 6 demonstrated an association between transfusion and increased complications; and 10 of 18 demonstrated an association between transfusion and decreased cancer survival. CONCLUSION: This review supports the evidence linking perioperative blood transfusions to negative outcomes. The most convincing association was with post-operative complications, some association with long-term cancer outcomes, and no convincing association with mortality. These findings support the initiation, and further study, of restrictive transfusion protocols.
Subject(s)
Blood Loss, Surgical/prevention & control , Erythrocyte Transfusion/adverse effects , Hepatectomy/adverse effects , Liver Neoplasms/surgery , Postoperative Hemorrhage/prevention & control , Aged , Aged, 80 and over , Blood Loss, Surgical/mortality , Erythrocyte Transfusion/mortality , Female , Hepatectomy/mortality , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local , Odds Ratio , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/mortality , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Desmin intermediate filaments (DIFs) form an intricate meshwork that organizes myofibers within striated muscle cells. The mechanisms that regulate the association of desmin to sarcomeres and their role in desminopathy are incompletely understood. Here we compare the effect nebulin binding has on the assembly kinetics of desmin and three desminopathy-causing mutant desmin variants carrying mutations in the head, rod, or tail domains of desmin (S46F, E245D, and T453I). These mutants were chosen because the mutated residues are located within the nebulin-binding regions of desmin. We discovered that, although nebulin M160-164 bound to both desmin tetrameric complexes and mature filaments, all three mutants exhibited significantly delayed filament assembly kinetics when bound to nebulin. Correspondingly, all three mutants displayed enhanced binding affinities and capacities for nebulin relative to wild-type desmin. Electron micrographs showed that nebulin associates with elongated normal and mutant DIFs assembled in vitro. Moreover, we measured significantly delayed dynamics for the mutant desmin E245D relative to wild-type desmin in fluorescence recovery after photobleaching in live-cell imaging experiments. We propose a mechanism by which mutant desmin slows desmin remodeling in myocytes by retaining nebulin near the Z-discs. On the basis of these data, we suggest that for some filament-forming desmin mutants, the molecular etiology of desminopathy results from subtle deficiencies in their association with nebulin, a major actin-binding filament protein of striated muscle.
Subject(s)
Desmin/metabolism , Intermediate Filaments/metabolism , Muscle Proteins/metabolism , Myofibrils/metabolism , Animals , Binding, Competitive , Cells, Cultured , Chick Embryo , Cytoskeleton/metabolism , Desmin/genetics , Desmin/ultrastructure , Dogs , Electrophoresis, Polyacrylamide Gel , Fluorescence Recovery After Photobleaching , Humans , Intermediate Filaments/genetics , Intermediate Filaments/ultrastructure , Kinetics , Microscopy, Confocal , Microscopy, Electron, Transmission , Muscle Proteins/genetics , Muscle Proteins/ultrastructure , Mutation , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Myofibrils/ultrastructure , Protein Binding , Sarcomeres/metabolismABSTRACT
PURPOSE OF REVIEW: Antipsychotic therapy has been eclipsed by high rates of noncompliance; the problem was attributed to a lack of efficacy and the burden of side effects of neuroleptics. This review sought to examine whether the arrival of second generation (atypical) antipsychotic drugs with low side-effect liability and improved efficacy has helped to positively reinforce compliance behaviour among people treated for schizophrenia. RECENT FINDINGS: The number of studies that systematically examined compliance behaviour and its determinants during antipsychotic drug therapy is disappointingly low. A review of relevant clinical trials, drug dispensation databases and observational studies yielded equivocal results. The data have failed to substantiate the notion that novel antipsychotic drug use leads to improved medication compliance and favourable clinical outcomes. SUMMARY: A decade of clinical experience and research indicates that compliance behaviour has only marginally improved since the introduction of second generation antipsychotic drugs. Noncompliance in schizophrenia is a complex maladaptive pattern of behaviour determined by personal beliefs, illness-related factors, social attributes and health system variables. The reinforcing value of antipsychotic drugs may be less relevant in enhancing treatment compliance and influencing the natural history of schizophrenia.
