Evidence that heparin but not hirudin reduces PAI-1 expression in cultured human endothelial cells

Heparin and other antithrombotic drugs besides their anticoagulant action could have a profibrinolytic effect. We have analyzed the effect of unfractionated heparin (UFH) and hirudin on PAI-1 gene expression in human umbilical vein endothelial cells (HUVEC). Cells were stimulated with UFH (1 and 10 IU/ml) and hirudin (20 and 100 TIU/ml). Samples were obtained before and 2, 6, and 24 hours after stimulation. mRNA analysis was conducted by reverse transcription followed by polymerase chain reaction, and PAI-1 antigen was determined by ELISA. Addition of UFH (10 IU/ml) to HUVEC resulted in a decrease of PAI-1 mRNA at 6 hours (40% reduction) and 24 hours (60% reduction) and PAI-1 antigen. Hirudin, however, did not modify significantly the PAI-1 mRNA nor the inhibitor secretion. The addition of UFH (10 or 100 IU/ml) to endotoxin-stimulated HUVEC also reduced the increased PAI-1 mRNA and antigen secretion (45%), whereas no effect could be observed with hirudin. Our results suggest that UFH, but not hirudin, by reducing the endothelial expression of PAI-1 might have a profibrinolytic effect

Variations in “rescuability” of immunoglobulin molecules from different forms of human lymphoma: implications for anti-idiotype vaccine development

Idiotypic (Id) vaccination has shown promising results in patients with follicular lymphoma (FL). However, it still remains unclear whether the same approach might be suitable for the treatment of other B-cell malignancies. For this reason, we recently performed an interim analysis of patients proposed to receive this treatment at our center. The feasibility of employing idiotype vaccines was evaluated for five different B-cell malignancies in their first relapse, both in terms of induction and fusion, as well as overall treatment. Our data suggest that, unlike follicular lymphoma (87%), this approach is not feasible to treat other B-cell malignancies (0–20%) such as mantle cell, small lymphocytic, diffuse large cell and Burkitt’s lymphoma (P < 0.01). The main difficulties encountered were technical problems related to the survival of idiotype-producing hybridomas (83%) and the early loss of idiotype production by growing hybridomas (17%). However, it remains possible that an idiotype vaccine might still be produced through molecular means for most, if not all cases of relapsing B-cell malignancies

Active immunotherapy in the treatment of haematological neoplasias

Abstract The continuous search for therapeutic approaches that improve the conventional treatments of neoplasms, together with an improved understanding of the immune system, has led in recent years to the development of Immunotherapy. Basically, a distinction can be made between two forms of immunotherapy: passive immunotherapy, which consists in the transfer of antibodies or cells previously generated in vitro that are directed against the tumour, and active immunotherapy, which attempts to activate in vivo the immune system and induce it to elaborate a specific response against the tumor antibodies. Hematological neoplasms, specifically some B lymphomas, express in their membrane an immunoglobulin that is considered a specific antigen of the tumour, which is why these diseases have become the ideal target for immunotherapy treatments. There are many alternatives, ranging from protein vaccines, which have already shown clinical benefits, to those of the second generation, which make use of the new techniques of molecular biology to increase the efficacy of the vaccines and obtain their production in a quicker and less costly way, but with which there are not yet definitive clinical results

Formal support for informal caregivers to older persons with dementia through the course of the disease: an exploratory, cross-sectional study

Background: In European countries, knowledge about availability and utilization of support for informal caregivers caring for older persons (>= 65 years) with dementia (PwD) is lacking. To be able to evaluate and develop the dementia support system for informal caregivers to PwD, a survey of European support systems and professionals involved is needed. The aim of this study was to explore support for informal caregivers to PwD in European countries. We investigated the availability and utilization of support in each of the participating countries, and the professional care providers involved, through the dementia disease. Methods: A mapping system was used in 2010-2011 to gather information about estimations of availability, utilization, and professional providers of support to informal caregivers caring for PwD. Data collected was representing each country as a whole. Results: There was high availability of counselling, caregiver support, and education from the diagnosis to the intermediate stage, with a decrease in the late to end of life stage. Utilization was low, although there was a small increase in the intermediate stage. Day care and respite care were highly available in the diagnosis to the intermediate stage, with a decrease in the late to end of life stage, but both types of care were utilized by few or no caregivers through any of the disease stages. Professionals specialized in dementia (Bachelor to Master's degree) provided counselling and education, whereas caregiver support for informal caregivers and day care, respite care, and respite care at home were provided by professionals with education ranging from upper secondary schooling to a Master's degree. Conclusions: Counselling, caregiver support, and education were highly available in European countries from diagnosis to the intermediate stage of the dementia disease, decreasing in the late/end of life stages but were rarely utilized. Countries with care systems based on national guidelines for dementia care seem to be more aware of the importance of professionals specialized in dementia care when providing support to informal caregivers. Mapping the systems of support for informal caregivers of PwD is a valuable tool for evaluating existing systems, internationally, nationally and locally for policy making

Acquired potential N-glycosylation sites within the tumor-specific immunoglobulin heavy chains of B-cell malignancies

Background and Objectives. Among B-cell malignancies, follicular lymphomas (FL) more frequently show acquired, potential N-glycosylation sites (AGS) within tumor-specific immunoglobulin. The aim of this study was to extend this observation and to evaluate the pattern of presentation of AGS within five different forms of B-cell lymphoma. Design and Methods. We sequenced the tumor-specific immunoglobulin heavy chain variable region fragment, including complementarity-determining regions 2 and 3, of forty-seven consecutive patients with a B-cell malignancy enrolled in idiotype vaccine clinical trials. This sequencing approach is known to allow the identification of most AGS. We then statistically analyzed differences in presentation pattern, in terms of tumor histology, immunoglobulin isotype, AGS location and amino acid composition. Results. All twenty-four FL cases presented with at least one AGS, whereas the vast majority of four B-cell lymphoma types other than FL did not. The non- FL group of tumors included four cases of Burkitt’s lymphoma, six of diffuse large cell lymphoma, seven mantle cell lymphomas and six small lymphocytic lymphomas. Most IgM-bearing follicular lymphoma cases featured their AGS within complementarity-determining region 2, as opposed to those bearing an IgG, which mostly displayed the AGS within complementarity- determining region 3. The vast majority of AGS located within either complementarity- determining region ended with a serine residue, whereas those located within framework regions mostly featured threonine as the last amino acid residue. Interpretation and Conclusions. In our series, all cases of FL had AGS within their tumor-specific immunoglobulin heavy chain variable regions. In contrast, most B-cell malignancies other than FL did not. Further studies are warranted in order to establish the possible meaning of these findings in terms of disease pathogenesis, their diagnostic value in doubtful cases and their potential implications for immunotherapy

Lessons from Our Patients: Development of a Warm Autopsy Program

Kaminski and colleagues discuss the lessons they have learned in establishing a warm autopsy program to advance research on idiopathic pulmonary fibrosis

Efficacy of tunnel technique in the treatment of localized and multiple gingival recessions: A systematic review and metaâ analysis

BackgroundTunnel technique (TUN) has recently gained popularity among clinicians for its promising clinical and esthetic results in treating gingival recession (GR) defects. However, evidence regarding the efficacy of the TUN is not yet conclusive. Therefore, the aim of the present systematic review and metaâ analysis was to investigate the predictability of TUN and its comparison to the coronally advanced flap (CAF) procedure.MethodsA literature search on PubMed, Cochrane libraries, EMBASE, and handâ searched journals through November 2017 was conducted to identify clinical studies investigating TUN for root coverage procedures. Only randomized controlled trials (RCTs) were considered for the metaâ analysis comparing TUN to CAF.ResultsA total of 20 articles were included in the systematic review and six in the metaâ analysis. The overall calculated mean root coverage (mRC) of TUN for localized and multiple GR defects was 82.75 ± 19.7% and 87.87 ± 16.45%, respectively. Superior results were found in maxillary and in Miller Class I and II GR defects. TUN outcomes may have been enhanced by splitâ thickness flap preparation and microsurgical approach. TUN and CAF had comparable mRC, complete root coverage (CRC), keratinized tissue gain, and root coverage esthetic score when varying combinations of graft material were evaluated. However, CAF demonstrated superior outcomes to TUN when the same graft (connective tissue or acellular dermal matrix) was used in both techniques.ConclusionsTUN is an effective procedure in treating localized and multiple GR defects. Limited evidence is available comparing TUN to CAF; however, CAF seemed to be associated with higher percentage of CRC than was TUN when the same grafts (connective tissue or acellular dermal matrix) were used in both techniques.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145520/1/jper10154.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145520/2/jper10154_am.pd

Master's level in primary health care education - students' and preceptors' perceptions and experiences of the alteration in the clinical areas

Abstract Background Many Western European countries are undergoing reforms with changes in higher education according to the Bologna declaration for Higher European Education Area. In accordance with these changes, the Master's degree was introduced in specialist nurse education in Sweden in 2007, and as a result changed the curriculum and modified theoretical and clinical areas. The aim of this study was to investigate students' and preceptors' perceptions and experiences of Master's level education in primary health care with a focus on the clinical area. Methods A descriptive design and qualitative approach was used. Interviews with ten students and ten preceptors were performed twice, before and after the clinical practice period. Interviews were audio-recorded, transcribed verbatim and themes formulated. Results Students perceived alteration in the content of the education at the Master's level such as more independence and additional assignments. The preceptors perceived benefits with the Master's level but were unsure of how to transform theoretical and abstract knowledge into practice. Writing the Master's thesis was seen by students to take time away from clinical practice. For some students and preceptors the content of the Master's level clinical practice area was experienced as vague and indistinct. The students had not expected supervision to be different from earlier experiences, while preceptors felt higher demands and requested more knowledge. Both students and preceptors perceived that education at the Master's level might lead to a higher status for the nurses' profession in primary health care. Conclusions Students and preceptors experienced both advantages and disadvantages concerning the change in specialist nurse education in primary health care at the Master's level. The altered educational content was experienced as a step forward, but they also questioned how the new knowledge could be used in practice. The relevance of the Master's thesis was questioned. Supervision was seen by students as an introduction to the work of the district nurses' work. Preceptors perceived high demands and did not feel enough qualified for student supervision. Both groups considered it an advantage with the change in education that could result in higher status for nurses working in primary health care.</p