Anticonvulsants-induced chorea: a role for pharmacodynamic drug interaction?

AbstractChorea is a rare side effect of anticonvulsants. We describe three patients who developed chorea secondary to anticonvulsant combination use. A mechanism to explain this finding is proposed.After identification of an index case with anticonvulsant-induced chorea, we reviewed the electronic data base records for all patients with seizures followed in the epilepsy clinics at our university-based hospital for cases of dyskinesia associated with anticonvulsants. Two additional patients , one adult and one pediatric patient were identified.Three patients developed chorea while receiving combination anticonvulsants. Two patients had transient chorea that resolved with withdrawal of one of the drugs. All three patients were using phenytoin and lamotrigine in combination when the chorea started, chorea improved with tapering one of the medications.Polytherapy with certain anticonvulsants may predispose patients to drug-induced chorea. A particular increased risk was seen with combinations that have phenytoin and lamotrigine. This could be due to an additive or a synergistic effect on central dopaminergic pathways

Striatal Acetylcholine-Dopamine Imbalance in Parkinson Disease:In Vivo Neuroimaging Study with Dual-Tracer PET and Dopaminergic PET-Informed Correlational Tractography

Previous studies of animal models of Parkinson disease (PD) suggest an imbalance between striatal acetylcholine and dopamine, although other studies have questioned this. To our knowledge, there are no previous in vivo neuroimaging studies examining striatal acetylcholine-dopamine imbalance in PD patients. Using cholinergic and dopaminergic PET (F-18-fluoroethoxybenzovesamicol [F-18-FEOBV] and C-11-dihydrotetrabenazine [C-11-DTBZ], respectively) and correlational tractography, our aim was to investigate the acetylcholine-dopamine interaction at 2 levels of dopaminergic loss in PD subjects: integrity loss of the nigrostriatal dopaminergic white matter tract and loss at the presynaptic-terminal level. Methods: The study involved 45 subjects with mild to moderate PD (36 men, 9 women; mean age, 66.3 +/- 6.3 y, disease duration, 5.8 +/- 3.6 y; Hoehn and Yahr stage, 2.2 +/- 0.6) and 15 control subjects (9 men, 6 women; mean age, 69.1 +/- 8.6 y). PET imaging was performed using standard protocols. We first estimated the integrity of the dopaminergic nigrostriatal white matter tracts in PD subjects by incorporating molecular information from striatal C-11-DTBZ PET into the fiber tracking process using correlational tractography (based on quantitative anisotropy [QA], a measure of tract integrity). Subsequently, we used voxel-based correlation to test the association of the mean QA of the nigrostriatal tract of each cerebral hemisphere with the striatal F-18-FEOBV distribution volume ratio (DVR) in PD subjects. The same analysis was performed for C-11-DTBZ DVR in 12 striatal subregions (presynaptic-terminal level). Results: Unlike C-11-DTBZ DVR in striatal subregions, the mean QA of the nigrostriatal tract of the most affected hemisphere showed a negative correlation with a striatal cluster of F-18-FEOBV DVR in PD subjects (corrected P = 0.039). We also found that the mean F-18-FEOBV DVR within this cluster was higher in the PD group than in the control group (P = 0.01). Cross-validation analyses confirmed these findings. We also found an increase in bradykinesia ratings associated with increased acetylcholine-dopamine imbalance in the most affected hemisphere (r = 0.41, P = 0.006). Conclusion: Our results provide evidence for the existence of striatal acetylcholine-dopamine imbalance in early PD and may provide an avenue for testing in vivo effects of therapeutic strategies aimed at restoring striatal acetylcholine-dopamine balance in PD

Modeling He-rich subdwarfs through the hot-flasher Scenario

We present 1D numerical simulations aimed at studying the hot-flasher scenario for the formation of He-rich subdwarf stars. Sequences were calculated for a wide range of metallicities and physical assumptions, such as the stellar mass at the moment of the helium core flash. This allows us to study the two previously proposed flavors of the hot-flasher scenario ("deep" and "shallow" mixing cases) and to identify a third transition type. Our sequences are calculated by solving simultaneously the mixing and burning equations within a diffusive convection picture, and in the context of standard mixing length theory. We are able to follow chemical evolution during deep-mixing events in which hydrogen is burned violently, and therefore able to present a homogeneous set of abundances for different metallicities and varieties of hot-flashers. We extend the scope of our work by analyzing the effects of non-standard assumptions, such as the effect of chemical gradients, extra-mixing at convective boundaries, possible reduction in convective velocities, or the interplay between difussion and mass loss. Particular emphasis is placed on the predicted surface properties of the models. We find that the hot-flasher scenario is a viable explanation for the formation and surface properties of He-sdO stars. Our results also show that, during the early He-core burning stage, element diffusion may produce the transformation of (post hot-flasher) He-rich atmospheres into He-deficient ones. If this is so, then we find that He-sdO stars should be the progenitors of some of the hottest sdB stars.Comment: 13 pages, including 8 figures and 6 tables. Accepted for publication in A&A. Replaced to match the final version, including a note added in proof regarding PG 1544+48

How the vision of a clinician and an educator brought the MA Dental Law and Ethics course to life.

This paper reflects on an educational development that is Dental Law and Ethics course as the course approaches its 5th anniversary. The authors outline their personal journey into developing and delivering this course as well share best practice in relation to teaching and learning dental postgraduate students who may approach the subject in different ways. It also highlights the vision behind this provision and how it is received by dental practitioners. The paper shares the learners’ perception of topics such as ethics in comparison to law, and it highlights the perspective of both authors in teaching and following the students’ journey in this course

The ubiquitous nature of the Horizontal Branch second U-jump: A link with the Blue Hook scenario?

In a previous paper we reported on a discontinuity in the extreme horizontal branch (EHB) of the Galactic globular cluster NGC6752, which we called the second U-jump. This feature was attributed to a combination of post zero-age horizontal branch evolution and diffusion effects. In this follow-up study we analyze other EHB clusters and show that the second U-jump is a common feature among EHB clusters reaching T_{eff}\ge 23,000K, and that its onset in different clusters converges around T_{eff}\sim 21,000\pm3,000K. We also present near-ultraviolet diagrams of \omega Cen and NGC2808, the only two objects with spectroscopically confirmed ``blue hook'' stars (T_{eff}\ge 35,000K). We confirm predictions of a photometric discontinuity separating late from early-helium flashers. Moreover, we present empirical evidence that the second U-jump population might be mainly composed by early-helium flashers. Lastly, we revisit the discussion on the ubiquitous nature of the gaps and jumps so far identified in the blue HB tails, suggesting a possible discrete nature of the distribution in temperature of the HB stars.Comment: 15 pages, 8 figures. Higher resolution version available via ftp at ftp://ftp.pd.astro.it/pub/momany/momany.tar A&A accepte

Dopaminergic Nigrostriatal Connectivity in Early Parkinson Disease:In Vivo Neuroimaging Study of C-11-DTBZ PET Combined with Correlational Tractography

Previous histopathologic and animal studies have shown axonal impairment and loss of connectivity of the nigrostriatal pathway in Parkinson disease (PD). However, there are conflicting reports from in vivo human studies. C-11-dihydrotetrabenazine (C-11-DTBZ) is a vesicular monoamine type 2 transporter PET ligand that allows assessment of nigrostriatal presynaptic dopaminergic terminal integrity. Correlational tractography based on diffusion MRI can incorporate ligand-specific information provided by C-11-DTBZ PET into the fiber-tracking process. The purpose of this study was to assess the in vivo association between the integrity of the nigrostriatal tract (defined by correlational tractography) and the degree of striatal dopaminergic denervation based on C-11-DTBZ PET. Methods: The study involved 30 subjects with mild to moderate PD (23 men and 7 women; mean age, 66 +/- 6.2 y; disease duration, 6.4 +/- 4.0 y; Hoehn and Yahr stage, 2.1 +/- 0.6; Movement Disorder Society [MDS]-revised Unified Parkinson Disease Rating Scale [UPDRS] [I-III] total score, 43.4 +/- 17.8) and 30 control subjects (18 men and 12 women; mean age, 62 +/- 10.3 y). C-11-DTBZ PET was performed using standard synthesis and acquisition protocols. Correlational tractography was performed to assess quantitative anisotropy (QA; a measure of tract integrity) of white matter fibers correlating with information derived from striatal C-11-DTBZ data using the DS! Studio toolbox. Scans were realigned according to least and most clinically affected cerebral hemispheres. Results: Nigrostriatal tracts were identified in both hemispheres of PD patients. Higher mean QA values along the identified tracts were significantly associated with higher striatal C-11-DTBZ distribution volume ratios (least affected: r = 0.57, P = 0.001; most affected: r = 0.44, P = 0.02). Lower mean QA values of the identified tract in the LA hemisphere associated with increased severity of bradykinesia sub-score derived from MDS-UPDRS part III (r = 0.42; P = 0.02). Cross-validation revealed the generalizability of these results. Conclusion: These findings suggest that impaired integrity of dopaminergic nigrostriatal nerve terminals is associated with nigrostriatal axonal dysfunction in mild to moderate PD. Assessment of nigrostriatal tract integrity may be suitable as a biomarker of earlyor even prodromal-stage PD

Delayed-onset disseminated BCG disease causing a multi-system illness with fatal mycotic aortic aneurysm

CASE: We report a case of disseminated BCG infection, diagnosed two years after BCG infusion for bladder cancer. Our patient, a 74-year-old male, was referred with an 18-month history of fevers, weight loss and intermittent confusion. Prior to referral, the patient had multiple hospital admissions for evaluation of fever of unknown origin, confusion, and fatigue. He was treated for several acute infections, whilst extensive investigations did not identify a focal cause of the persistent fever. During this period two aneurysms, iliac and aortic, were found and stented. Both were presumed mycotic, but no positive microbiology arose from either. He presented again with fever and confusion and was found to have a left sided pleural effusion, which was drained, and broad-spectrum antibiotics started, but his fever and inflammatory markers did not settle. Mycobacterium tuberculosis PCR on a pleural fluid sample returned a positive result, and later cultures from the same fluid grew Mycobacterium species which whole genome sequencing identified as Mycobacterium Bacillus Calmette-Guérin (BCG). Despite a number of adverse events with anti-BCG medications, the patient was established on four medications (rifampicin/isoniazid/ethambutol/levofloxacin) with symptomatic improvement. He re-presented four months later with abdominal pain and was found to have an inoperable leaking thoracic aortic sac from deterioration of his mycotic aneurysm. Following discussion with the patient and his family he was managed palliatively and died two days later. DISCUSSION: The learning points from this case are to consider disseminated BCG in patients presenting with pyrexia of unknown origin following reported intravesical BCG treatment for bladder malignancy in the years prior to presentation. Mycotic aneurysms are a rare but serious complication of disseminated BCG with a high mortality

Excitation of the 3.071mm Hyperfine Line in Li-Like 57-Fe in Astrophysical Plasmas

As noted first by Sunyaev & Churazov (1984), the 3.071 mm hyperfine line from $^{57}Fe^{+23}$ might be observable in astrophysical plasmas. We assess the atomic processes which might contribute to the excitation of this line. We determine the intensity of the hyperfine line from an isothermal, coronal plasma in collisional ionization equilibrium and for a coronal plasma cooling isobarically due to its own radiation. Comparisons of the hyperfine line to other lines emitted by the same ion, Fe$^{+23}$, are shown to be useful for deriving the isotopic fraction of $^{57}$Fe. We calculate the ratios of the hyperfine line to the 2s--2p EUV lines at 192 \AA and 255 \AA, and the 2s--3p X-ray doublet at 10.6 \AA.Comment: 28 pages text+figures, Accepted to ApJ in Jan 98, also at http://www.astro.virginia.edu/~nld2n/research.htm

RAT J0455+1305: A rare hybrid pulsating subdwarf B star

We present results on the second-faintest pulsating subdwarf B (sdB) star known, RAT J0455+1305, derived from photometric data obtained in 2009. It shows both short and long periods oscillations, theoretically assigned as pressure and gravity modes. We identify six short-period frequencies (with one being a combination) and six long-period frequencies. This star is the fourth hybrid sdB star discovered so far which makes it of special interest as each type of mode probes a different part of the star. This star is similar to the sdB hybrid pulsator Balloon 090100001 in that it exhibits short-period mode groupings, which can be used to identify pulsation parameters and constrain theoretical models.Comment: published in MNRA