Investigation on the origin of hot electrons in laser plasma interaction at shock ignition intensities.

Shock Ignition is a two-step scheme to reach Inertial Confinement Fusion, where the precompressed fuel capsule is ignited by a strong shock driven by a laser pulse at an intensity in the order of [Formula: see text] W/cm[Formula: see text]. In this report we describe the results of an experiment carried out at PALS laser facility designed to investigate the origin of hot electrons in laser-plasma interaction at intensities and plasma temperatures expected for Shock Ignition. A detailed time- and spectrally-resolved characterization of Stimulated Raman Scattering and Two Plasmon Decay instabilities, as well as of the generated hot electrons, suggest that Stimulated Raman Scattering is the dominant source of hot electrons via the damping of daughter plasma waves. The temperature dependence of laser plasma instabilities was also investigated, enabled by the use of different ablator materials, suggesting that Two Plasmon Decay is damped at earlier times for higher plasma temperatures, accompanied by an earlier ignition of SRS. The identification of the predominant hot electron source and the effect of plasma temperature on laser plasma interaction, here investigated, are extremely useful for developing the mitigation strategies for reducing the impact of hot electrons on the fuel ignition.

Factors affecting the biodiversity of historical landscape elements: detailed analyses from three case studies in Slovakia.

A direct, positive correlation between biodiversity and the traditional agricultural landscape is evident on the national or regional scale. It is mostly conditioned by higher landscape diversity and less intensive farming. We have carried out research on a detailed scale at plot level (productive plots of arable lands, grasslands, vineyards, orchards, and unproductive agrarian landforms (mostly field margins) such as terraced slopes, terraced steps, heaps, mounds, and unconsolidated walls) in three traditional agricultural landscapes: the mountain village Liptovská Teplicka, the vineyard landscape in Svätý Jur, and dispersed settlements in a submontane area in Hrinová. We determined the statistical significance of the impact of the selected landscape ecological factors (a set of factors concerning land use and management, agrarian landforms and relief properties) on the distribution of vegetation and selected invertebrate groups (spiders, millipedes, grasshoppers, and crickets). We also explored whether maintaining traditional land use and traditional management helped to enhance the biodiversity. We found that the management regime is the most important factor determining the species composition of vascular plants and all studied animal groups. Also, present land use and agrarian landforms character (type, skeleton content, continuity) are significant factors. Our expectation of a positive relationship between biodiversity and the maintaining traditional land use and traditional management was, in general, not confirmed: such a relation was only found in Svätý Jur for biodiversity of spiders.

Alterations in allocation and composition of lipid classes in Euonymus fruits and seeds.

The spindle tree (Euonymus europaeus L.) is a much-branched deciduous shrub or small tree. Its fruit capsules contain seeds with remarkably high content of oil interesting for industry, especially the 3-acetyl-1,2-diacyl-sn-glycerols (AcDAG) synthesized by a specific acetyl-CoA diacylglycerol acetyltransferase. The distribution and amount of individual triacylglycerols (TAG) and especially acetyl-triacylglycerols (AcDAG) in Euonymus fruit have previously been assigned to specific tissues. Using anatomical and microscopical observations, we studied the fruit morphology, and for the first time, we identified a more detailed allocation of oil bodies in individual tissue structures. Thin layer chromatography separation of extracts from immature and mature fruits confirmed TAG and AcDAG as the most abundant lipid classes in both endosperm and embryo, followed by fatty acids and polar lipids. The abundance of fatty acids was further studied in the TAG and AcDAG fractions using gas chromatography. Data revealed particular FAs in both fractions allocated in tissue-specific manner and/or as indicators of maturation of E. europaeus seeds. While the abundance of cis-vaccenic-, linoleic as well as α-linolenic acids in the AcDAG structures generally drop with maturation in both embryo and endosperm, content of oleic acid increases. Abundance of cis-vaccenic acid in TAG was recorded in immature endosperm. For embryo, the abundance of stearic acid in AcDAG and oleic acid in TAG fraction was distinctive. Deeper understanding of underlying metabolic processes will be essential for targeted metabolic engineering and/or application for oilseed crops.

Gender-related differences observed among immune cells in synovial fluid in knee osteoarthritis.

OBJECTIVE: There is no existing comprehensive report on the cellular composition of synovial fluids (SFs) from knee osteoarthritis (OA). We therefore aimed to characterise the immune cell composition in SFs from knee OA (KOA) and in subgroups according to gender. DESIGN: The immunophenotyping of monocyte/macrophage lineage cells, T and B cells, NK cells, neutrophils, dendritic and mast cells (MC) present in SFs from 53 patients (24 males/29 females) with KOA was performed using 6-colour flow cytometry. RESULTS: SFs from patients with OA contained 90% hematopoietic cells. Lymphocytes were the predominant cell population (44.8%) in the SFs of OA patients, with CD4+ T lymphocytes being more prevalent than CD8+ T cells (CD4+/CD8+ ratio = 1.3). Within the monocyte/macrophage lineage gating, monocytes accounted for 33.9%, macrophages 14.8%, myeloid dendritic cells 16.4%. The rest of the hematopoietic cells were comprised of neutrophils (8%), NK cells (3.8%), T regulatory cells (1.2%), plasmacytoid dendritic cells (1.1%), mast cells (0.3%). In OA females, a higher percentage of CD4+ T cells (P = 0.023), macrophages (P = 0.012), and a lower percentage of monocytes (P = 0.008) and CD8+ T cells (P = 0.002) were detected in comparison to OA males. CONCLUSIONS: Based on the immune cell composition of SFs, data mining analysis revealed distinct phenotypes (monocyte- and lymphocyte-predominant) within each gender group. This first study on the cellular complexity of SFs in KOA showed marked differences between male and female patients. The findings give a rational starting point for patient stratification according to their phenotypes, as is required for phenotype-specific treatment strategies.

The effects of short-term norepinephrine up-titration on hemodynamics in cardiogenic shock.

A higher mean arterial pressure (MAP) achieved by norepinephrine up-titration may improve organ blood flow in critically ill, whereas norepinephrine-induced afterload rise might worsen myocardial function. Our aim was to assess the effects of norepinephrine dose titration on global hemodynamics in cardiogenic shock. We prospectively evaluated 12 mechanically ventilated euvolemic patients (aged 67 +/- 12 years) in cardiogenic shock (10 patients acute myocardial infarction, 1 patient dilated cardiomyopathy, 1 patient decompensated aortic stenosis). Hemodynamic monitoring included arterial and Swan-Ganz catheters. The first data were obtained at MAP of 65 mm Hg, then the norepinephrine dose was increased over 40 min to achieve MAP of 85 mm Hg. Finally, the norepinephrine-dose was tapered over 40 min to achieve MAP of 65 mm Hg. Norepinephrine up-titration increased MAP to the predefined values in all patients with concomitant mild increase in filling pressures and heart rate. Systemic vascular resistance increased, whereas cardiac output remained unchanged. During norepinephrine down-titration, all hemodynamic parameters returned to baseline values. We observed no changes in lactate levels and mixed venous oxygen saturation. Our data suggest that short-term norepinephrine dose up-titration in cardiogenic shock patients treated or pretreated with inotropes was tolerated well by the diseased heart.

Intravenous immunoglobulin for myasthenia gravis.

BACKGROUND: Myasthenia gravis is an autoimmune disease in which autoantibodies interfere with neuromuscular transmission. As with other autoimmune diseases, people with myasthenia gravis would be expected to benefit from intravenous immunoglobulin (IVIg). OBJECTIVES: The objective of this review was to examine the efficacy of intravenous immunoglobulin for treating exacerbations of myasthenia gravis or for chronic myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease GroupTrials Register (April 2007) and MEDLINE (January 1966 to May 2007) using 'myasthenia gravis' and 'intravenous immunoglobulin' as the search terms. SELECTION CRITERIA: We included all randomised or quasi-randomised trials in which intravenous immunoglobulin was compared with no treatment, placebo or plasma exchange, in people with myasthenia gravis. DATA COLLECTION AND ANALYSIS: One review author extracted the data and two others checked these data and the source from which they were derived. For methodological reasons, no formal meta-analysis was performed. MAIN RESULTS: We identified six randomised controlled trials, all of which investigated short-term benefit. A trial of IVIg compared with placebo including 51 patients provided evidence for the effectiveness of IVIg in myasthenia gravis worsening. A study of 87 participants with exacerbation found no statistically significant difference between immunoglobulin and plasma exchange after two weeks. A study of 12 participants with moderate or severe myasthenia gravis treated in a crossover design trial found no statistically significant difference in the efficacy of immunoglobulin and plasma exchange after four weeks. A study with 15 participants with mild or moderate myasthenia gravis found no statistically significant difference in efficacy of IVIg and placebo after six weeks. A study included 33 participants with moderate exacerbations of myasthenia gravis and showed no statistically significant difference in the efficacy of IVIg and methylprednisolone. The last trial including 173 people with myasthenia gravis exacerbations, showed no superiority of IVIg 1 g/kg on two consecutive days over IVIg 1 g/kg on a single day. AUTHORS' CONCLUSIONS: In exacerbation of myasthenia gravis, one randomised controlled trial of IVIg versus placebo demonstrated the efficacy of IVIg and another did not show a significant difference between IVIg and plasma exchange. Another showed no significant difference in efficacy between 1 g/kg and 2 g/kg of IVIg. A further, but underpowered, trial showed no significant difference between IVIg and oral methylprednisolone. In chronic myasthenia gravis, there is insufficient evidence from randomised trials to determine whether IVIg is efficacious. More research is needed to determine whether IVIg reduces the need for corticosteroids as suggested by two case series.

Intravenous immunoglobulin for myasthenia gravis.

BACKGROUND: Myasthenia gravis is an autoimmune disease in which autoantibodies interfere with neuromuscular transmission. As with other autoimmune diseases, people with myasthenia gravis would be expected to benefit from intravenous immunoglobulin. OBJECTIVES: The objective of this review was to examine the efficacy of intravenous immunoglobulin for treating exacerbations of myasthenia gravis or for chronic myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (March 2005) and MEDLINE (January 1966 to March 2005) using 'myasthenia gravis' and 'intravenous immunoglobulin' as the search terms. SELECTION CRITERIA: We included all randomised or quasi-randomised trials in which intravenous immunoglobulin was compared with no treatment, placebo or plasma exchange, in people with myasthenia gravis. DATA COLLECTION AND ANALYSIS: One author extracted the data and the two others checked these data and the source from which they were derived. For methodological reasons, no formal meta-analysis was performed. MAIN RESULTS: We identified five randomised controlled trials, all of which investigated short-term benefit. The first study of 87 participants with exacerbation found no statistically significant difference between immunoglobulin and plasma exchange after two weeks. The second study of 12 participants with moderate or severe myasthenia gravis treated in a crossover design trial found no statistically significant difference in the efficacy of immunoglobulin and plasma exchange after four weeks. The third study with 15 participants with mild or moderate myasthenia gravis found no statistically significant difference in efficacy of intravenous immunoglobulin and placebo after six weeks. The fourth study terminated early. It included 33 participants with moderate exacerbations of myasthenia gravis and showed no statistically significant difference in the efficacy of intravenous immunoglobulin and methylprednisolone. The fifth trial including 173 people with myasthenia gravis exacerbations, showed no superiority of intravenous immunoglobulin 1 g/kg on two consecutive days over intravenous immunoglobulin 1 g/kg on a single day. AUTHORS' CONCLUSIONS: In severe exacerbations of myasthenia gravis, one randomised controlled trial did not show a significant difference between intravenous immunoglobulin and plasma exchange. Another showed no significant difference in efficacy between 1 g/kg and 2 g/kg of intravenous immunoglobulin. A further trial showed no significant difference between intravenous immunoglobulin and oral methylprednisolone. In chronic myasthenia gravis, there is insufficient evidence from randomised trials to determine whether intravenous immunoglobulin is efficacious. More research is needed to determine whether intravenous immunoglobulin reduces the need for steroids as suggested by two case series.

Corticosteroids for myasthenia gravis.

BACKGROUND: Although widely accepted as an appropriate immunosuppressive therapy, the efficacy of glucocorticosteroid treatment has only rarely been tested in controlled studies. OBJECTIVES: To assess the efficacy of glucocorticosteroids or adrenocorticotrophic hormone (ACTH) medication in autoimmune myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register in July 2004, MEDLINE (from January 1966 to June 2004) and EMBASE (from January 1980 to June 2004). We also checked the bibliographies in reviews and the randomised trials and contacted their authors to identify additional published and unpublished data. SELECTION CRITERIA: From the articles identified we selected those open or controlled studies which allowed us to assess the outcome of treated and untreated patients at definite endpoints. Types of studies: quasi-randomised or randomised controlled trials. TYPES OF PARTICIPANTS: patients with myasthenia gravis of all ages and all degrees of severity. Types of interventions: any form of glucocorticosteroids or adrenocorticotrophic hormone treatment. Types of outcome measures:Primary outcome(1) improvement after at least three months in either the weakest muscles or all muscles. Secondary outcomes(1) proportion of patients improved after at least six months(2) proportion of patients in remission(3) number of episodes of worsening during the first six months(4) acetylcholine receptor antibody titres after at least three months of therapy. DATA COLLECTION AND ANALYSIS: Three authors extracted the data from the selected articles and one other checked them. MAIN RESULTS: A trial of adrenocorticotrophic hormone (43 patients) did not show any advantage compared with placebo for the treatment of ocular myasthenia gravis. Two double-blind trials compared prednisone with placebo for generalised myasthenia gravis. In the first (13 patients), the improvement was slightly greater in the prednisone group at six months. In the second (20 patients) which was a short-term trial, the improvement was significantly greater at two weeks. Two trials compared glucocorticosteroids with azathioprine (41 and 10 patients respectively). In one of these the rate of treatment failure was greater in the prednisone group. In a trial of glucocorticosteroids versus intravenous immunoglobulin (33 patients) no differences in treatment responses were encountered during a treatment period of 14 days. An open trial (39 patients) evaluating different corticosteroid doses revealed a shorter time to improvement in the high-dose group. However only limited evidence can be drawn from the available randomised controlled trials due to numerous and important methodological flaws. AUTHORS' CONCLUSIONS: Limited evidence from randomised controlled trials suggests that corticosteroid treatment offers significant short-term benefit in myasthenia gravis compared with placebo. This supports the conclusions of observational studies and expert opinion. Limited evidence from randomised controlled trials does not show any difference in efficacy between corticosteroids and either azathioprine or intravenous immunoglobulin.

[Consolidation of therapy of acute myeloid leukemia with the AML-BFM 93 protocol in children in the Czech Republic]. / Sjednocení lécby detí s akutní myeloidní leukémií v Ceské republice podle protokolu AML-BFM 93.

BACKGROUND: Acute myeloid leukemia (AML) in children is rare. Although more resistant to chemotherapy than acute lymphoblastic leukemia, its responsiveness and survival rates have considerably improved during the last 15 years by virtue of intensification of chemotherapy and due to the better supportive care. Relapses still remain the main cause of treatment failure. Management of children with AML was unified in the Czech Republic in 1993 according to AML-BFM 93 Study protocol. METHODS AND RESULTS: Treatment results were evaluated in 61 patients, of whom 45 (73.8%) achieved complete remission. Five-year event-free-survival (EFS) was found in 42.3%, and overall survival was 45.3%. Prognosis of the standard-risk patients was significantly better than in the high-risk group (EFS 62.5% vs. 29.7%, p = 0.03). The most important prognostic factor was the early treatment response. Compared to chemotherapy, allogeneic stem-cell transplantation did not significantly improve the outcome of high-risk patients. CONCLUSIONS: Treatment results of children with AML in the Czech Republic are comparable to those achieved by leading leukemia study groups in the world. The aim of the next study is to increase the complete-remission rate by reducing early deaths.

Genetic control of autoantibody expression in autoimmune myasthenia gravis: role of the self-antigen and of HLA-linked loci.

Autoantibodies against the muscle acetylcholine receptor (AChR) play an essential role in the pathophysiology of autoimmune myasthenia gravis (MG). Their serum titers, however, vary considerably among patients. Our aim was to investigate whether their variation might be explained by genetic factors. Using different methods, we have obtained strong evidence for a three-locus association influencing autoantibody titers in MG patients with thymus hyperplasia or with a normal thymus. Two of the loci, one encoding the AChR alpha-subunit, the other encoding the alpha-chain of the class II antigen-presentation molecule, HLA-DQ, demonstrated interaction to determine high autoantibody titers. The third locus was associated with the 8.1 ancestral HLA haplotype. It exerted an additive effect and it is postulated to have a nonantigen specific immunoregulatory function. Our study demonstrates for the first time that polymorphism of an autoantigen gene may quantitatively modify the immune response against it. Altogether, the data lend support to a three-gene model to explain autoantibody expression in a subset of MG patients.

[Seronegative myasthenia gravis]. / Myasthénie séro-négative.

Six to 20 p.cent of patients with generalized myasthenia gravis and 30 to 50 p.cent of those with ocular myasthenia gravis do not have anti AchR antibodies. Strict clinical, pharmacological and electrophysiological criteria are needed for the diagnosis of sero-negative myasthenia gravis. Sero-negative myasthenia gravis is an autoimmune disorder. But thymic hyperplasia is generally absent. Antibodies directed against the muscle receptor of tyrosine kinase (anti MuSK antibodies) were recently demonstrated in 40 to 70 p.cent of patients with sero-negative myasthenia gravis. Sero-negative and sero-positive myasthenia gravis may be clinically very similar. But sero-negative myasthenia gravis may express predominantly severe oculobulbar weakness or mainly neck, shoulder and respiratory muscle weakness. Sero-negative myasthenia gravis is never associated with thymoma. Sero-negative myasthenia gravis responds to immunodulation but perhaps less well than sero-positive myasthenia gravis.

Association of the gene encoding the delta-subunit of the muscle acetylcholine receptor (CHRND) with acquired autoimmune myasthenia gravis.

The muscle acetylcholine receptor (AChR) is the main target self-antigen in acquired autoimmune myasthenia gravis (MG). Here, we investigated an association of MG with the CHRND gene encoding the delta-subunit of the AChR. Using a microsatellite repeat located in the second intron of the gene, we observed a preferential transmission of the allele 268 in 114 one-generation families with one myasthenic child (Pc=0.0154). This allele was also over-represented in a group of 350 unrelated nonthymoma MG patients (OR=1.78, P=0.038), but not in 84 thymoma patients, compared to 168 healthy controls. Moreover, among nonthymoma patients, those lacking serum anti-titin antibodies appeared to be best associated (OR=2.07, P=0.017). In contrast, there was no distortion in the transmission of a single-nucleotide substitution polymorphisms (SNPs) in the 3' untranslated region of CHRND nor in that of two SNPs located in the closely linked CHRNG gene, 4.5 kb telomeric to CHRND. The data warrant a detailed investigation of CHRND polymorphism in MG patients.

[Myasthenia gravis and pregnancy. Report on 13 cases]. / Myasthénie et grossesse: à propos de 13 grossesses.

OBJECTIVES: To evaluate our experience of myasthenia during pregnancy. MATERIALS AND METHODS: Retrospective study in a tertiary care university hospital including pregnant women affected by myasthenia gravis and who delivered in the obstetrical tertiary center. Medical and delivery reports were analyzed. RESULTS: Between 1994 and 2002, 12 women, age 31 (25-36), delivered 14 children. One women delivered twice, and there was one twin pregnancy. Clinical symptoms of myasthenia worsened in five. One was admitted twice to the intensive care unit during her pregnancy. Two were admitted to intensive care unit during the first month of post-partum. Gestational age at birth was 39.3 weeks (38-40.6), all birth weights were normal: 3329 g (2660-4520). Six women delivered vaginally, two by instrumental extraction and five by cesarean section. Apgar score was normal for all infants: 9/10. The level of anti-acetylcholine receptor antibodies (anti AchR) was high: 36.4 nM/L (0-46.8) (normal below 0.6 nM/L), but was not related to neonatal outcome. Three children presented neonatal myasthenia. CONCLUSION: We recommend obstetrical monitoring in tertiary centers for pregnant women with myasthenia gravis because of the risk of neonatal myasthenia. Measurement of anti-acetylcholine receptor antibodies may be useful. Pediatric and maternal observation is necessary in the first days of post partum.

Standards of measurements in myasthenia gravis.

Valid and reliable measurements of muscle impairment are needed to assess therapeutic efficacy in patients with generalized myasthenia gravis. Several muscle scoring systems have been proposed for assessing muscle strength in such patients. The aim of the present study is to assess the validity and interobserver agreement of these muscle scores.

[Improved results in children with acute lymphoblastic leukemia treated with the ALL-BFM 90 protocol in the Czech Republic]. / Zlepsení výsledku lécby detí s akutní lymfoblastickou leukémií podle protokolu ALL-BFM 90 v Ceské republice.

BACKGROUND: Prognosis of children with acute lymphoblastic leukaemia (ALL)--the most common cancer in childhood, has improved remarkably over the last 40 years. The authors report the treatment outcome in children with ALL cured according to ALL-BFM 90 Study protocol in the Czech Republic during the first half of nineties. METHODS AND RESULTS: Children aged 0-18 years were included into the study in 10 centers between 1990 to 1996. Patients were classified into standard-risk (SR), medium-risk (MR) and high-risk (HR) group according to initial leukaemic burden, early treatment response, and genotype of leukaemia. Duration of the chemotherapy was two years. Treatment results were evaluated in 352 children. With a median follow-up of 7.3 years, event-free-survival (EFS) was 71.3% and overall survival 76.4%. EFS was 80.3%, 74% and 28.2% in SR, MR and HR group, respectively. Relapse was diagnosed in 17.8% of the patients. CONCLUSIONS: The treatment outcome of children with ALL improved significantly (p = 0.0045) compared to the previous study ALL-BFM 83 (EFS 62%). These results are comparable to those achieved by leading leukaemia study groups in the world.

Intravenous immunoglobulin for myasthenia gravis.

BACKGROUND: Myasthenia gravis is an autoimmune disease. In up to 90 per cent of cases IgG autoantibodies to the nicotinic acetylcholine receptor are detectable which mediate the neuromuscular transmission disorder. As with other autoimmune diseases, patients would be expected to benefit from intravenous immunoglobulin. Case series and two randomised controlled trials suggest that intravenous immunoglobulin may be beneficial. OBJECTIVES: The objective of this review is to examine the efficacy of intravenous immunoglobulin for treating exacerbations of myasthenia gravis or for chronic myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (21 July 2002) and MEDLINE (January 1966 to July 2002) using 'myasthenia gravis' and 'intravenous immunoglobulin' as the search terms. SELECTION CRITERIA: All randomised or quasi-randomised trials in which intravenous immunoglobulin was compared with no treatment, placebo or plasma exchange, in people with myasthenia gravis who were diagnosed by an internationally accepted definition. DATA COLLECTION AND ANALYSIS: One author extracted the data and the two others checked these data and the source from which they were derived. For methodological reasons, no formal meta-analysis was performed. MAIN RESULTS: We identified four randomised controlled trials (147 participants in total), all investigating short-term benefit. In the first study of 87 people with myasthenia gravis exacerbation, comparing intravenous immunoglobulin and plasma exchange, there was no statistically significant difference between the efficacy of the two treatments after two weeks. In the second study 12 people with moderate or severe myasthenia gravis were treated in a cross-over design trial with intravenous immunoglobulin or plasma exchange: no statistically significant difference in the efficacy of the two treatments was found after four weeks. In the third study 15 people with mild or moderate myasthenia gravis received intravenous immunoglobulin or a placebo: no significant difference in efficacy of intravenous immunoglobulin or placebo was found six weeks after treatment. The last study, which included 33 people with moderate exacerbations of myasthenia gravis, compared intravenous immunoglobulin and methylprednisolone and showed no statistically significant difference in the efficacy of the two treatments. REVIEWER'S CONCLUSIONS: One randomised controlled trial did not show a significant difference between intravenous immunoglobulin and plasma exchange for treatment of severe exacerbations of myasthenia gravis. There is no evidence from randomised controlled trials to determine whether intravenous immunoglobulin for moderate or severe myasthenia gravis improves functional outcome or has a sparing effect on steroid dosage, nor is there sufficient evidence to favour intravenous immunoglobulin over steroids in moderate exacerbations. Further randomised controlled trials are needed.

[Effect of amifostine on reducing acute toxicity of megachemotherapy of tumors in children]. / Vliv amifostinu na redukci akutní toxicity pri protinádorové megachemoterapii detí.

BACKGROUND: Amifostine (WR-2721, Ethyol) is a chemoprotective agent. There is little experiences with amifostine application in megachemotherapy in children. We evaluated amifostine effect on the reduction of the acute toxicity. METHODS AND RESULTS: Retrospective comparison of patients who received amifostine with the control group (72 vs. 72). Amifostine 750 mg/m2 was given 15 minute before cytostatic dose and regularly each eight hours if we administered cytostatics continuously. Megachemotherapy schedule included melfalan, carboplatin, cyklophosphamid, vepesid, busulfan, thiotepa and karmustin. Type of graft: peripheral stem cells 56 vs. 29, bone marrow 8 vs. 30, combination 8 vs. 13. Nonhematological toxicity: mucositis p = 0.047, hepatotoxicity p < 0.001, nephrotoxicity p = 0.005. Hematological toxicity: engraftment D + 12 vs. D + 15 (p < 0.001), amount of erythrocyte transfusions 3 vs. 6 (p < 0.001), platelet transfusions 7 vs. 9 (p = 0.06), days when number of platelets reaches 20,000 without substitution D + 15 vs. D + 22 (p < 0.001). The only statistically difference was in the in total amount of platelets (p = 0.032), when we calculated patients, who received peripheral stem cells. Number of hospitalization days 14 vs. 18 (p = 0.016), days with antibiotics 14 vs. 18 (p = 0.016), number of febrile days 6 vs. 7 (p = 0.51). CONCLUSIONS: Amifostine reduces mucosal, liver and kidney damage. The graft type could affect hematological results.

Plasma exchange for myasthenia gravis.

BACKGROUND: Myasthenia gravis is an autoimmune disease mediated by auto-antibodies direct against the nicotinic receptor for acetylcholine. Patients would be expected to benefit from plasma exchange. Non-randomised studies suggest that plasma exchange is beneficial in the short term. OBJECTIVES: To examine the efficacy of plasma exchange in the short and long term treatment of myasthenia gravis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register (searched 17 July 2002) and MEDLINE (January 1966 to June 2002) for randomised controlled trials using myasthenia gravis as the search term. We checked the bibliographies in reports of randomised trials and contacted one author to identify additional published or unpublished data. SELECTION CRITERIA: Types of studies: All randomised or quasi-randomised studies. TYPES OF PARTICIPANTS: All patients with myasthenia gravis who were diagnosed by an internationally accepted definition. Types of intervention: Treatment with plasma exchange alone or combined with steroids or immunosuppressive drugs. Types of outcome measures: PRIMARY OUTCOME MEASURE: ~bullet~patients treated for exacerbation: change in a specific muscle score after plasma exchange; ~bullet~patients treated for chronic myasthenia gravis: change in a functional scale. SECONDARY OUTCOME MEASURES: ~bullet~patients treated for exacerbation: change in a functional scale and percentage weaned from mechanical ventilation; ~bullet~patients treated for chronic myasthenia gravis: percentage in remission by the end of one year after first plasma exchange; ~bullet~adverse events. DATA COLLECTION AND ANALYSIS: One author extracted the data and the two others checked them. Since there was only one trial no formal meta-analysis was required. MAIN RESULTS: We identified one randomised controlled trial. Improvement in a quantitative muscle score was not significantly greater in patients treated with plasma exchange and prednisone than in patients treated with prednisone alone one month after onset of treatment. More relapses were observed in the plasma exchange and prednisone group in the first year as compared with the prednisone alone group. Problems in recruitment and matching of patients entered into this trial limit the conclusions that can be drawn. On the other hand,experience from many non-randomised studies suggests that plasma exchange is beneficial in myasthenia gravis. Consequently the relative benefits of plasma exchange are still unconfirmed. REVIEWER'S CONCLUSIONS: There are no adequate randomised controlled trials but many case series report short-term benefit from plasma exchange in myasthenia gravis, especially in myasthenic crisis. There are no adequate randomised controlled trials to determine whether plasma exchange improves the long-term outcome for myasthenia gravis. Further research is need to compare plasma exchange with alternative short-term treatments for myasthenic crisis and to determine the value of long-term plasma exchange for treating myasthenia gravis.

Linkage of HLA to myasthenia gravis and genetic heterogeneity depending on anti-titin antibodies.

BACKGROUND: MG is an autoimmune disease of the neuromuscular junction. MG with thymus hyperplasia has been associated with, but not genetically linked to, the HLA-DR3 haplotype. OBJECTIVE: To re-evaluate the association of HLA with MG in 656 patients with generalized disease and to test linkage of HLA to MG with thymus hyperplasia. METHOD: Patients were genotyped for HLA-DRB1. Data analysis included case-control comparisons after subgrouping patients by thymus histopathology. The transmission of parental alleles to MG offspring with thymus hyperplasia was studied in simplex families using the transmission/disequilibrium test (TDT) as a test of linkage. RESULTS: MG with thymus hyperplasia was positively associated with DR3 (OR = 4.5, p = 1 x 10(-6)) and negatively associated with DR7 (OR = 0.28, p = 1 x 10(-6)), based on both case-control comparisons and TDT. No association was detected with thymomas. Conversely, patients who lacked thymus anomalies but expressed anti-titin antibodies (ATA) had an increase of DR7 (OR = 2.08, p = 4 x 10(-3)) and a decrease of DR3 (OR = 0.33, p = 9 x 10(-3)). CONCLUSIONS: The authors established linkage of HLA to MG and thymus hyperplasia, defining the MYAS1 locus. Moreover, DR3 and DR7, or closely linked genes, have opposing effects on MG phenotypes. Nonthymomatous patients with ATA may be a pathogenetically distinct subset of MG patients.