Pharmacokinetics of Cefuroxime are not Significantly Altered by Cardiopulmonary Bypass in Children

Poster presented at: SPA/AAP PEDIATRIC ANESTHESIOLOGY 2010 - Winter Meeting; April 2010; San Antonio, TX

Progression of motor subtypes in Huntington’s disease. a 6-year follow-up study

The objective of this study is to investigate the progression of predominantly choreatic and hypokinetic-rigid signs in Huntington's disease (HD) and their relationship with cognitive and general functioning over time. The motor signs in HD can be divided into predominantly choreatic and hypokinetic-rigid subtypes. It has been reported in cross-sectional studies that predominantly choreatic HD patients perform better on functional and cognitive assessments compared to predominantly hypokinetic-rigid HD patients. The course of these motor subtypes and their clinical profiles has not been investigated longitudinally. A total of 4135 subjects who participated in the European HD Network REGISTRY study were included and classified at baseline as either predominantly choreatic (n = 891), hypokinetic-rigid (n = 916), or mixed-motor (n = 2328), based on a previously used method. The maximum follow-up period was 6 years. The mixed-motor group was not included in the analyses. Linear mixed models were constructed to investigate changes in motor subtypes over time and their relationship with cognitive and functional decline. Over the 6-year follow-up period, the predominantly choreatic group showed a significant decrease in chorea, while hypokinetic-rigid symptoms slightly increased in the hypokinetic-rigid group. On the Total Functional Capacity, Stroop test, and Verbal fluency task the rate of change over time was significantly faster in the predominantly choreatic group, while on all other clinical assessments the decline was comparable for both groups. Our results suggest that choreatic symptoms decrease over time, whereas hypokinetic-rigid symptoms slightly increase in a large cohort of HD patients. Moreover, different motor subtypes can be related to different clinical profiles

Exploring genetic factors involved in huntington disease age of onset. E2F2 as a new potential modifier gene

Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor

NMDA receptor gene variations as modifiers in Huntington disease: a replication study.

Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the entire cohort. Yet, when subjects were stratified by AO subtypes, we found nominally significant evidence for an association of the GRIN2A rs1969060 variation and the GRIN2B rs1806201 variation. These findings further implicate the N-methyl D-aspartate receptor subtype genes as loci containing variation associated with AO in HD

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS:Results from the nordic NMDSG08A phase II trial

This prospective phase II study evaluated the efficacy of azacitidine (Aza) + erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo + granulocyte colony stimulation factors for 48 weeks and a transfusion need of ≥ 4 units over 8 weeks were included. Aza 75mgm -2 d-1, 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received ≥ one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza + Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n = 3) and DNMT3A (n = 4) were only observed in nonresponders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations

Improved analysis of bacterial CGH data beyond the log-ratio paradigm

<p>Abstract</p> <p>Background</p> <p>Existing methods for analyzing bacterial CGH data from two-color arrays are based on log-ratios only, a paradigm inherited from expression studies. We propose an alternative approach, where microarray signals are used in a different way and sequence identity is predicted using a supervised learning approach.</p> <p>Results</p> <p>A data set containing 32 hybridizations of sequenced versus sequenced genomes have been used to test and compare methods. A ROC-analysis has been performed to illustrate the ability to rank probes with respect to Present/Absent calls. Classification into Present and Absent is compared with that of a gaussian mixture model.</p> <p>Conclusion</p> <p>The results indicate our proposed method is an improvement of existing methods with respect to ranking and classification of probes, especially for multi-genome arrays.</p

‘Sub-Prime’ Water, Low-Security Entitlements and Policy Challenges in Over-Allocated River Basins: the Case of the Murray–Darling Basin

Environmental policy is often implemented using market instruments. In some cases, including carbon taxing, the links between financial products and the environmental objectives, are transparent. In other cases, including water markets, the links are less transparent. In Australia’s Murray–Darling Basin (MDB), financial water products are known as ‘entitlements’, and are similar to traditional financial products, such as shares. The Australian water market includes ‘Low Security’ entitlements, which are similar to ‘sub-prime’ mortgage bonds because they are unlikely to yield an amount equal to their financial worth. Nearly half the water purchased under the Murray–Darling Basin Plan for environmental purposes is ‘Low Security’. We suggest that the current portfolio of water held by the Australian Government for environmental purposes reflects the mortgage market in the lead-up to the global financial crisis. Banks assumed that the future value of the mortgage market would reflect past trends. Similarly, it is assumed that the future value of water products will reflect past trends, without considering climate change. Historic records of allocations to ‘Low Security’ entitlements in the MDB suggest that, in the context of climate change, the Basin Plan water portfolio may fall short of the target annual average yield of 2075 GL by 511 GL. We recommend adopting finance sector methods including ‘hedging’ ‘Low Security’ entitlements by purchasing an additional 322–2755 GL of ‘Low Security’, or 160–511 GL of ‘High Security’ entitlements. Securing reliable environmental water is a global problem. Finance economics present opportunities for increasing the reliability of environmental flows

Hepatic mitochondrial dysfunction in Friedreich Ataxia

<p>Abstract</p> <p>Background</p> <p>Mitochondrial dysfunction due to respiratory chain impairment is a key feature in pathogenesis of Friedreich ataxia. Friedreich ataxia affects the nervous system, heart and pancreas.</p> <p>Methods</p> <p>We assessed hepatic mitochondrial function by ¹³C-methionine-breath-test in 16 Friedreich ataxia patients and matched healthy controls.</p> <p>Results</p> <p>Patients exhaled significantly smaller amounts of ¹³CO₂over 90 minutes. Maximal exhaled percentage dose of ¹³CO₂recovery was reduced compared to controls.</p> <p>Conclusions</p> <p>¹³C-methionine-breath-test indicates subclinical hepatic mitochondrial dysfunction in Friedreich ataxia but did not correlate with GAA repeat lengths, disease duration or disease severity.</p

Supracubital perineurioma misdiagnosed as carpal tunnel syndrome: case report

BACKGROUND: Perineuriomas have been defined as tumorous lesions of the peripheral nerves which derive from perineurial cell proliferation and may be associated with abnormalities on chromosome 22. CASE PRESENTATION: Three years after a painful cubital vein procaine injection, a 33 year-old man developed a median nerve lesion, initially diagnosed as carpal tunnel syndrome. Symptoms progressed despite appropriate surgery. Clinical and electrophysiological re-evaluation revealed a fusiform mass at the distal upper arm, confirmed by MRI. Immunohistochemical studies classified the tumor as a mixed perineurioma and neuroma. CONCLUSIONS: Perineurioma mixed with neuroma may potentially caused by the previous trauma or cytotoxic effects of procaine