Oculopalatal tremor: current concepts and new observations.

PURPOSE OF REVIEW: Oculopalatal tremor (OPT) is an acquired disorder resulting from the interruption of a specific brainstem circuitry, the dentato-rubro-olivary pathway or Guillain-Mollaret triangle. The recent literature on OPT and olivary hypertrophy was reviewed with specific interest regarding causes, diagnostic procedures, physiopathology and therapies. RECENT FINDINGS: OPT is associated with inferior olivary hypertrophy, and recent findings have provided a better understanding of its intimate mechanisms. A dual-mechanism model, combining an oscillator (inferior olive) and a modulator/amplifier (cerebellum), best explains the development of OPT. Electrotonic coupling and specific Ca channels contribute to oscillations of inferior olivary nucleus neurons in OPT. Improvement of visual symptoms can be achieved with oral gabapentin or memantine. SUMMARY: Both the neuronal circuitry and the physiopathology of OPT are now better understood. This opens up an era of specific therapy for this rare cause of disabling oscillopsia.

New observations on Permian stratigraphy in Greece and geodynamic implication

New detailed stratigraphic and micropaleontological works on the famous exposures of Permian rocks in Hydra rich in Foraminifera, allows to define the stratigraphy of other outcrops in Aegina, Salamis, Attica and Chios. A synthetic section is presented which is characterized by the development of 3 successive carbonate platforms during the Permian and by 4 main tectonostratigraphic events. The youngest of these events marks the closure of the Paleotethyan ocean and the collision of a former Gondwanian/Cimmerian passive margin in the S with an active margin in the N.

Population pharmacokinetics in chronic myeloid leukaemia patients: observations under field-conditions

Introduction: Therapeutic drug monitoring (TDM) of imatinib has been increasingly proposed for chronic myeloid leukaemia (CML) patients, as several studies have found a correlation between trough concentrations (Cmin) >=1000ng/ml and improved response. The pharmacological monitoring project of EUTOS (European Treatment and Outcome Study) was launched to increase the availability of imatinib TDM, standardize labs, and validate proposed Cmin thresholds. Using the collected data, the objective of this analysis was to characterize imatinib Population pharmacokinetics (Pop-PK) in a large cohort of European patients, to quantify its variability and the influence of demographic factors and comedications, and to derive individual exposure variables suitable for further concentration-effect analyses.¦Methods: 4095 PK samples from 2478 adult patients were analyzed between 2006 and 2010 by LC-MS-MS and considered for Pop-PK analysis by NONMEM®. Model building used data from 973 patients with >=2 samples available (2590 samples). A sensitivity analysis was performed using all data. Available comedications (27%) were classified into inducers or inhibitors of P-glycoprotein, CYP3A4/5 and organic-cation-transporter-1 (hOCT-1).¦Results: A one-compartment model with linear elimination, zero-order absorption fitted the data best. Estimated Pop-PK parameters (interindividual variability, IIV %CV) for a 40-year old male patient were: clearance CL = 17.3 L/h (37.7%), volume V = 429L (51.1%), duration of absorption D1 = 3.2h. Outliers, reflecting potential compliance and time recording errors, were taken into account by estimating an IIV on the residual error (35.4%). Intra-individual residuals were 29.1% (proportional) plus ± 84.6 ng/mL (additive). Female patients had a 15.2% lower CL (14.6 L/h). A piece-wise linear effect of age estimated a CL of 18.7 L/h at 20 years, 17.3 L/h at 40 and 13.8 L/h at 60 years. These covariates explained 2% (CL) and 4.5% (V) of IIV variability. No effect of comedication was found. The sensitivity analysis expectedly estimated increased IIV, but similar fixed effect parameters.¦Conclusion: Imatinib PK was well described in a large cohort of CML patients under field conditions and results were concordant with previous studies. Patient characteristics explain only little IIV, confirming limited utility of prior dosage adjustment. As intra-variability is smaller than inter-patient variability, dose adjustment guided by TDM could however be beneficial in order to bring Cmin into a given therapeutic target.

Risk factor impact on blood flow velocities and clinical outcomes of stented cervical and intracranial stenoses: preliminary observations.

OBJECTIVES: The role of angioplasty/stenting procedures, neurointerventionist experience, vascular risk factors, medical treatment and blood flow velocities were analysed to identify possible causes of intra-stent restenosis (ISR) following stenting of cervical and/or intracranial arteries, assuming progressive atherosclerosis to be the shared mechanism in both territories. Patients. 26 cerebrovascular patients subjected to stenting of severe (≥85%) symptomatic or asymptomatic carotid stenoses or moderate-to-severe (≥50%) intracranial or vertebral stenoses were included. METHODS: Clinical, radiological and ultrasonographic follow-up data were analysed retrospectively. RESULTS: Overall, stenting of the internal carotid artery (ICA) induced significant reductions in peak systolic velocities at 2 years (96±31cm/s vs. 358.2±24.9cm/s at baseline). The procedure-related ischemic complications rate was 7.4% (one hemispheric stroke and one TIA). The rate of ISR≤50% was 8% in the ICA at 2 years; was 50% in the common carotid artery (CCA) at 1 year, with concomitant distal ICA stenosis in 75% of CCA stenting, but all ISR were asymptomatic. Patients with ISR of the ICA were significantly younger (56.8±4.5 vs. 71.3±3.6 years, P=0.042) and had significantly more risk factors (5.5±0.9 vs. 3±0.3, P=0.012). No ISR≥70% was detected. CONCLUSIONS: ISR is relatively infrequent and, when present, it is mild and asymptomatic. Restenosis is more frequent in younger patients and those with several risk factors, and it may also be related to stenting of previous carotid endarterectomy.

Observations de populations marquées de la musaraigne aquatique Neomys fodiens (Insectivora, Mammalia)

Three populations of the European water shrew Neomy fodiens have been observed by live-trapping, one of them during twelve months. During highest populations density a local maximum of 21 individuals have been caught. Recapture frequency from month to month was less than 50%, probably due to a weak trappability and an important dispersal behaviour. During the winter all three populations disappeared. Change in habitat or change in behaviour might be responsible for the lack of trapping siccess in the cold period.