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The International Prognostic Scoring System (IPSS) remains the most commonly used system for risk classification in myelodysplastic syndromes (MDSs). The IPSS gives more weight to blast count than to cytogenetics. However, previous publications suggested that cytogenetics are underweighted in the IPSS. Here we investigate the prognostic impact of cytogenetic subgroups compared with that of bone marrow blast count in a large, multicentric, international patient cohort.
This cross-sectional study was conducted using data collected on all patients in the four state-operated psychiatric hospitals in Michigan using a comprehensive assessment instrument, the interRAI Mental Health. All patients taking both VPA and APs (n = 200) were compared to a control group of patients taking APs without VPA (n = 426). Patients were assessed for the presence of the following surrogate indicators of metabolic syndrome: weight gain; high body mass index (BMI greater than 30 kg/m(2)); very high BMI (BMI greater than 40 kg/m(2)); a diagnosis of diabetes mellitus; use of a prescribed statin medication; diagnosis of hyperlipidemia or dyslipidemia; hypertension; or the combination of any three of these factors: high BMI, hyperlipidemia or dyslipidemia, diabetes, and hypertension. Analysis also included assessment of the effect of VPA dosage on metabolic side effects.
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Subjects receiving lithium, carbamazepine, and/or valproate were identified from biochemistry laboratory data. Ninety-eight of these subjects had major depressive disorder (N = 20) or bipolar disorder (N = 78) (DSM-IV) and gave informed consent to participate in a structured clinical interview to assess their medication adherence and the factors that influenced it.
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In the model analysis, adjunctive quetiapine with lithium or valproate was associated with a 54% reduction in the occurrence of acute mood events, a 29% reduction in acute mood event-related hospitalization costs, and a 4% improvement in QALY gains, with 5% lower total direct costs than placebo + lithium/valproate. The incremental cost-effectiveness ratios (in year-2007 pound) were 506 per additional acute mood event avoided, 4261 per additional acute mood event-related hospitalization prevented, and -7453 per additional QALY gained. The sensitivity analyses indicated that these results were robust.
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Epigenetic silencing of the tumor suppressor gene, RARβ2, through histone deacetylation has been established as an important process of cervical carcinogenesis. This pivotal role has led to the suggestion that a combination of retinoids selective for RARβ2 with histone deacetylase (HDAC) inhibitors may have therapeutic potential. Valproic acid (VPA), a HDAC inhibitor, has a critical role in the regulation of gene expression through histone acetylation and causes transformed cells to undergo growth arrest, differentiation, and apoptosis. Therefore, we hypothesized that the combination of VPA and ATRA could restore RARβ2 expression, thus resulting in enhanced anti-neoplastic activity in cervical cancer. Here, we show that VPA combined with ATRA led to hyperacetylation of histone H3 and a significant alteration of gene expression in cervical cancer cells, including RARβ2 gene expression, which was upregulated 50- to 90-fold. The combination therapy effectively inhibited the growth of cervical cancer cells more than the single agent treatment both in vitro and in vivo. The additive effects were associated with a significant upregulation of p21(CIP1) and p53 as well as a pronounced decrease in p-Stat3. Furthermore, the combined treatment led to cell cycle arrest predominantly at the G1 phase, and it preferentially induced cell differentiation rather than apoptosis in cervical cancer cells. The differentiation program was determined by the presence of E-cadherinmediated adhesion and activation of the PI3K/Akt pathway. Taken together, these results provide new insight into the mechanisms of enhanced antitumor activity of the HDAC inhibitor and ATRA regimen, thus offering a new therapeutic strategy for cervical cancer patients.
[11C]Flumazenil PET provides a useful tool for investigating the hippocampal damage in vivo even in patients with no remarkable hippocampal abnormalities on quantitative MRI.
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Antiepileptic drugs are commonly given for perioperative prophylaxis after brain tumor surgery, and there has been growing interest in levetiracetam, a second-generation antiepileptic drug. This retrospective study compared the seizure outcomes, side effects and durability of levetiracetam with valproic acid after a craniotomy for supratentorial brain tumors.
The children receiving phenobarbital showed high levels of serum total cholesterol and low-density lipoprotein (LDL) cholesterol and low levels of triglycerides, while children treated with carbamazepine had high levels of total cholesterol, triglycerides, LDL and high-density lipoprotein (HDL) cholesterol. Children treated with valproate had low triglycerides and LDL cholesterol levels with high levels of HDL cholesterol. The patients treated with phenobarbital showed a normalization of all parameters after the end of therapy.