Forum (Genoa, Italy)最新文献

Liver transplantation is a surgical procedure offered to individuals with irreversible, near fatal liver disease. The timing of both transplantation listing and surgical engraftment are critical factors in the success of this endeavour. To accomplish each and maintain surgical survival rates without prematurely transplanting individuals to achieve excellent outcome statistics is an art that requires knowledge about the procedure and the natural history of the specific liver disease in question. Herein are the views of the transplant team at Loyola University of Chicago as to how this can be accomplished within the framework of the American experience, and the rules and regulations governing donor organ procurement and allocation in the United States.

Advances in computer-aided diagnosis, imaging techniques, DNA mutation analysis, virology, immunology and biochemistry have improved our understanding of chronic liver diseases and the possibilities for non-invasive diagnosis. Various medical therapies for chronic liver diseases and their complications have been developed recently, and their monitoring has also improved. This review focuses on these recent advances in non-invasive diagnosis and management of chronic liver diseases.

After defining the characteristics of ideological knowledge and knowledge based on research, the experimental work on illusory correlations, serial effects, difficulties in "grasping counter-examples" and prejudiced pseudo-knowledge is reported. This proves how ideology can develop from the very functioning of the cognitive processes (perception, thought) when it is not kept under critical scrutiny. The difference between ideological and scientific thought reflects the different social conditions behind the production of the two types of knowledge. The production of scientific knowledge is regulated by specific rules such as the logic of the experimental method and empirical references, and is animated by a depressive attitude ("I am responsible for matters within the confines of rules set by the research community") while the propositions of ideology are anti-empirical, shy away from counter-examples, are confusional, and are underpinned by an attitude that is potentially maniacal and omnipotent. The ideological factors that can have an effect on professional research are listed and it is shown how the results of this, once controlled, lose all ties to the ideology they may have been inspired by, to the extent that they constitute another sphere that is completely autonomous and independent.

A major problem in the assessment of liver function is represented by the quantification of the different aspects on which it relies (biosynthesis, drug metabolism, bile secretion, etc.) and of the clinical severity, with important prognostic implications. Another field that can be supported by quantification procedures is the histological evaluation of chronic hepatitis (necro-inflammatory activity and fibrosis). Finally, scoring systems can be usefully applied in clinical practice as a tool which supports medical decisions in very difficult diagnostic processes. In all the above considered fields, the scoring procedures have the important advantage to allow the standardisation of clinical procedures as well as to facilitate the statistical manipulation of data in controlled clinical trials. This paper reviews numerical scoring systems utilised in hepatology and their clinical applications.

The haematological diversity of myelodysplastic syndromes (MDS) mandates that therapeutic strategies for this disease be guided by an understanding of the disease biology. Insights into the pathobiology of this disease have given rise to novel treatment strategies which exploit basic biological disturbances. Myelodysplastic bone marrow progenitors from patients with low leukaemia burden display an accelerated senescence phenotype which is characterised by impaired response to trophic signals and premature apoptotic death of primitive haematopoietic progenitors. Elaboration of aptogenic cytokines such as TNF-alpha and IL-1beta may reinforce this sequence by up-regulating cellular expression of fas ligand and its cognate receptor, suppressing responsiveness to growth factor stimulation, and accelerating apoptotic cell death. Inactivation of p15 or other tumour suppressor genes antedate disease progression and the emergence of blast populations with reduced capacity for fas mediated cell death. Herein we review the current understanding of the pathobiology of MDS and promising strategies for therapeutic intervention.

There are several therapeutic options for myelodysplastic syndrome (MDS) patients but the potentially curative ones are only available for a minority of individuals. At present, in fact, the only two treatments that can prolong survival are allogeneic stem cell transplantation and intensive chemotherapy. The only two haematopoietic growth factors that can be useful in the treatment of selected MDS patients are recombinant human erythropoietin (rHuEpo) and G-CSF. Overall 15 to 20% of patients with MDS respond to rHuEpo treatment but the vast majority of responders are not transfusion-dependent and the doses required to achieve response are > 450 IU/kg per week. Factors predicting response include serum Epo levels <100 mU/ml, female gender and no or low need for transfusion. Recognising potential responders to rHuEpo can be extremely important in individual cases of MDS. G-CSF alone should be used only for short-term treatments. It may be administered to individual patients during an infective episode that does not respond to antibiotic therapy, particularly in the case of fungal infections. In addition, G-CSF may be employed for shortening the length of severe neutropenia following intensive chemotherapy. American and Scandinavian studies have shown that about 40% of MDS patients respond to a combined treatment of rHuEpo with G-CSF with amelioration of anaemia and that response can be maintained for a median duration of 24 months. Using pre-treatment serum Epo levels as a ternary variable (<100, 100-500 or > 500 U/l) and red blood cell transfusion need as a binary variable (<2 or > or =2 units per month), a predictive score for erythroid response to G-CSF plus rHuEpo can be obtained. This score can identify patients with a high probability of erythroid responses (about 75%). Due to the inadequacies of all current treatment modalities, participation in clinical trials should always be encouraged.

Clinical heterogeneity complicates therapy planning and makes it difficult to evaluate clinical trials in myelodysplastic syndromes (MDS). Thus, the development of a prognostic classification of MDS is of major clinical relevance, especially when considering the advanced age of most patients and the aggressiveness of the treatment modalities available. This review summarises the results of different studies focusing on prognostic factors in MDS and describes the relative advantages of the prognostic scoring systems that have been recently developed. This paper also discusses the prognostic factors of particular subtypes of patients. The percentage of marrow blasts, cytogenetic pattern and number and degree of cytopenias are the most powerful prognostic indicators in MDS. Although some limitations are evident, the recently developed scoring systems, and particularly the International Prognostic Scoring System, are extremely useful for predicting survival and acute leukaemic risk in individuals with MDS and should be incorporated into the design and analysis of therapeutic trials in these disorders. A risk-adapted treatment strategy is now possible and highly recommended for MDS patients.

Substantial progress has been made in risk assessment for patients with myelodysplastic syndromes (MDS). The development of accurate prognostic classification systems allows a risk-adapted treatment strategy in the individual patient. Allogeneic haematopoietic stem cell transplantation (HSCT) was considered until recently as the only curative approach for MDS. Recent data suggest that intensive chemotherapy programs, such as those employed for patients with AML, may lead to prolonged disease-free survival in a low but significant fraction of patients with high-risk MDS. Intensive post-remission chemotherapy, with or without autologous HSCT, may constitute an appropriate alternative for those patients lacking a suitable sibling donor or for older patients who are in remission after intensive chemotherapy. In this review we will summarise the results and future perspectives of intensive chemotherapy for high-risk MDS patients.

This review focuses on karyotypic and molecular findings of myelodysplastic syndromes (MDS). Genetic entities are distinct on the basis of structural (deletions, translocations, inversions) or numerical chromosomal abnormalities (trisomies, monosomies). New information about the amount and nature of malignant cells in MDS, as well as of genes rearranging in specific translocations, recently provided by molecular cytogenetics, are analysed. Integration of clinical-haematological classifications with cytogenetic and molecular findings is discussed

The cornerstone of therapeutic management for most patients with myelodysplastic syndrome (MDS) is supportive care, mainly in view of the average advanced age in MDS and the poor response to therapy. Due to the lack of satisfactory therapies, allogeneic stem cell transplantation is today the treatment of choice in the majority of young patients with histocompatible siblings. Results of treatment with allogeneic stem cell transplantation varies considerably depending on the stage of disease at transplantation and various clinical factors, such as the presence of cytogenetic abnormalities, age, and the percentage of blasts in the bone marrow at transplantation. Most patients may benefit optimally from an allogeneic stem cell transplantation when the transplant is performed as soon as an HLA-identical family member has been identified. Progression to more advanced leukaemic conditions will be associated with a higher failure rate mainly due to an increased incidence of relapse after transplantation. Delay of the transplant may be justified in a minority of patients with refractory anaemia without cytopenias or complex cytogenetic abnormalities. Patients who lack an HLA-identical family donor may be transplanted with either autologous stem cells or alternative allogeneic donors. The results are less compared to those obtained with histocompatible sibling transplantation due to an increased risk of relapse after autologous stem cell transplantation or a higher treatment-related mortality after transplantation with genotypically non-identical donors.