High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia

Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin- fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin- fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side- effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.      

Eltrombopag for the Treatment of Refractory Pure RBC Aplasia after Major ABO Incompatible Hematopoietic Stem Cell Transplantation

Pure RBC aplasia (PRCS) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many therapeutic options are available to treat this condition, including erythropoietin, rituximab, bortezomib, plasma exchange, immunoadsorption, donor lymphocyte infusion, mesenchymal stem cells, antithymocyte globulin, and high-dose steroids; however, treatment outcomes are often variable and can sometimes lead to disappointing results. In this brief article we report our experience with 2 patients with PRCA after major ABO-incompatible HSCT who were resistant to multiple therapeutic interventions and who eventually benefited from treatment with eltrombopag, a thrombopoietin mimetic approved by the US Food and Drug Administration for the treatment of patients with immune thrombocytopenic purpura or severe aplastic anemia refractory to immunosuppressive agents or not eligible for HSCT. Data from these 2 patients show that eltrombopag was effective in treating erythroid aplasia and transfusion dependence after HSCT in patients who did not benefit from multiple previous treatments. Moreover, eltrombopag was well tolerated, with only a transient thrombocytosis requiring dose adjustment and no evidence of clonal evolution. Based on the positive results obtained in these 2 patients, we suggest that eltrombopag may have a favorable effect on unilineage cytopenias such as PRCA. Further studies in a large proportion of patients are mandatory to confirm these preliminary results.     

The impact of detoxifying and repair gene polymorphisms on oxidative stress in ischemic stroke

Stroke is a multifactorial disease caused by the combination of certain risk factors and genetic factors. There are possible risk factors having important role in the pathogenesis of stroke. The most important environmental factors are cigarette smoking and oxidative stress which have different sources. GST (M1, T1, P1) have major roles in detoxification of the products of oxidative stress and they are polymorphic. DNA damages can also be repaired by repair enzymes such as OGG1 and XRCC1 which are highly polymorphic and have pivotal roles in repair systems. In the present study, we investigated that polymorphisms in genes involved in detoxification and DNA-repair pathways might modify the individual’s risk for ischemic stroke. Furthermore, the products of oxidative stress and antioxidant capacity were measured and the impact of gene polymorphism on them was evaluated. Our data showed that OGG1 Ser326Cys and XRCC1 Arg399Gln gene polymorphisms had impacts on the development of stroke.     

PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects

The PRAME (preferentially expressed antigen of melanoma) gene has been shown to be expressed in high levels in some solid tumors and hemopoietic neoplasias but not or only weakly expressed in normal tissues. It encodes an antigen recognized by autologous cytolytic T lymphocytes. PRAME is a good candidate for tumor immunotherapy and is a useful marker gene for detection of minimal residual disease (MRD). In this study, PRAME mRNA using real-time RT-PCR was studied in 74 adult cases with acute leukemia-68 had de-novo acute leukemia, 3 had chronic myeloid leukemia-blastic crisis (CML-BC), and 3 had myelodysplastic/myeloproliferative syndrome-blastic transformation (MDS/MPD-BT)-and the results were compared with 30 age-matched healthy volunteers. Nineteen of 74 cases with leukemia expressed PRAME, while only 2 controls showed weak expression. The prevalence of PRAME expression in AML and ALL cases was 30% and 17%, respectively. We did not find any important correlation between PRAME expression and clinical characteristics, such as age, sex, organomegaly/lymphadenopathy, Hb, WBC count, platelet count, LDH level, alkaline phosphatase, albumin, cell-surface antigens, response to therapy, or progression-free and overall survival. PRAME was monitored in 15 cases during remission and/or relapse. There was a good correlation between PRAME mRNA and hematological remission and/or relapse. Interestingly, PRAME was very high in one case with AML but was not found 3 months after allogeneic transplantation. PRAME mRNA is observed in about one-third of AML cases; it may be a useful marker to detect MRD, and it may also be a good predictor for the timing of donor lymphocyte infusions (DLI) in the post-transplant period in cases of molecular relapse.     

The combination of ınterleukin-10 -1082 and tumor necrosis factor α -308 or ınterleukin-6 -174 genes polymorphisms suggests an association with susceptibility to Hashimoto's thyroiditis

BackgroundThe etiopathogenesis of Hashimoto's thyroiditis (HT) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. The imbalance between pro- and anti-inflammatory cytokines may play a role in the etiology. The aim of the present study was to investigate whether cytokine gene polymorphisms are associated with HT, and to evaluate the relationship between genotypes and clinical/laboratory manifestation of HT.MethodsTumor necrosis factor α (TNFα) G-308A (rs 1800629), interleukin-6 (IL-6) G-174C (rs 1800795) and IL-10 G-1082A (rs 1800896) single nucleotide polymorphisms (SNPs) in DNA from peripheral blood leukocytes of 190 patients with HT and 231 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes.ResultsThere was no notable risk for HT afflicted by TNFα ? 308, IL-6 ? 174 and IL-10 ? 1082 polymorphisms alone. However, carriers of variant alleles of both IL-10 ? 1082 and TNFα ? 308 polymorphisms had four-fold times higher risk for HT in comparison with non-carriers. Additionally, concomitant presence of both mutant IL-10 ? 1082 A and IL-6 ? 174 C alleles raised three-fold the HT risk.ConclusionOur results suggest that the combined effects of TNFα ? 308, IL-6 ? 174 and IL-10 ? 1082 variant alleles may be more decisive to induce functional differences and modify the risk for HT.     

Multiple sclerosis patients—benefit-risk preferences: Serious adverse event risks versus treatment efficacy

Abstract Objective:   The aim of this study is to estimate the willingness of multiple sclerosis (MS) patients to accept life-threatening adverse event risks in exchange for improvements in their MS related health outcomes. Methods:   MS patients completed a survey questionnaire that included a series of choice-format conjoint tradeoff tasks. Patients chose hypothetical treatments from pairs of treatment alternatives with varying levels of clinical efficacy and associated risks. Results:   Among the 651 patients who completed the survey, delay in years to disability progression was the most important factor in treatment preferences. In return for decreases in relapse rates from 4 to 1 and increases in delay in progression from 3 to 5 years, patients were willing to accept a 0.38% annual risk of death or disability from PML, a 0.39% annual risk of death from liver failure or a 0.48% annual risk of death from leukemia. Conclusions:   Medical interventions carry risks of adverse outcomes that must be evaluated against their clinical benefits. Most MS patients indicated they are willing to accept risks in exchange for clinical efficacy. Patient preferences for potential benefits and risks can assist in decision-making.     

Prevalence of pleural effusions post orthotopic heart transplantation

BACKGROUND AND OBJECTIVE: The prevalence and natural history of pleural effusions occurring after orthotopic heart transplantations (OHT) are essentially unknown. The objective of this study was to determine the prevalence, laterality, size and prognosis of pleural effusions occurring after OHT. METHODS: Eighty-three patients who underwent OHT between August 1997 and January 2003 were screened retrospectively. CXR and chest CT scans of all patients were reviewed. Chart review was performed for patients with large effusions (occupying 25% or more of a hemithorax) with specific attention to thoracentesis results. RESULTS: Seventy-two patients were included in the study. Sixty-one (85%) developed an effusion at some time during the first 365 postoperative days. The majority of post-OHT effusions were bilateral and small, occupying less than 25% of the hemithorax. Pleural effusions occupying 25% or more of a hemithorax occurred in 17% (12/72) of the patients within 12 months of OHT. Overall, the majority of effusions resolved within the first year after transplantation. CONCLUSIONS: The prevalence of pleural effusions within 12 months following OHT is high (85%). Most effusions are small, bilateral and resolve within 1 year.     

Homocysteine levels in epileptic children receiving antiepileptic drugs

The aim of this study is to investigate the homocysteine, folic acid, and vitamin B(12) levels in epileptic children receiving antiepileptic drugs. A total of 25 children with idiopathic epilepsy (8 valproate, 11 carbamazepine, and 6 oxcarbazepine) and 10 healthy children were included in the study. The mean homocysteine, folic acid, and vitamin B(12) levels in the study group were 7.57 +/- 3.78 micromol/L (normal = 5-15 micromol/L), 10.19 +/- 4.05 ng/mL (normal = 3.0-17 ng/mL), and 428.20 +/- 256.12 pg/mL (normal = 193-983 pg/mL), respectively. The differences between the mean plasma homocysteine, folic acid, and vitamin B(12) levels of the study and control groups were not significant (P = .522; P = .855; P = .798, respectively). However, plasma homocysteine levels were higher than the normal cutoff point accepted for childhood in 4 (16%) of the study patients. Out of these 4 children, 3 were from the carbamazepine group and 1 was from the valproate group. Although the number of the study patients is limited, the authors recommend assessment of plasma homocysteine, serum vitamin B(12), and folic acid levels in children receiving enzyme-inducing antiepileptic drugs.