Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification.

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease

Basal cutaneous pain threshold in headache patients

The aim of this study was to analyze cutaneous pain threshold (CPT) during the interictal phase in headache patients, and the relationships between headache frequency and analgesic use. A consecutive series of 98 headache patients and 26 sex- and age-balanced controls were evaluated. Acute allodynia (AA) was assessed by Jakubowski questionnaire, and interictal allodynia (IA) by a skin test with calibrated monofilaments. AA is widely known as a symptom more present in migraine than in TTH spectrum: in our study this was confirmed only in cases of episodic attacks. When headache index rises towards chronicization, the prevalence of AA increases in both headache spectrums (χ2 13.55; p < 0.01). AA was associated with IA only in cases of chronic headache. When headache becomes chronic, mostly in presence of medication overuse, interictal CPT decreases and IA prevalence increases (χ2 20.44; p < 0.01), with closer association than AA. In MOH patients there were no significant differences depending on the diagnosis of starting headache (migraine or tension type headache) and, in both groups, we found the overuse of analgesics plays an important role: intake of more than one daily drug dramatically reduces the CPT (p < 0.05). Thus, when acute allodynia increases frequency, worsens or appears for the first time in patients with a long-standing history of chronic headache, it could reasonably suggest that the reduction of CPT had started, without using a specific practical skin test but simply by questioning clinical headache history. In conclusion, these results indicate that the role of medication overuse is more important than chronicization in lowering CPT, and suggest that prolonged periods of medication overuse can interfere with pain perception by a reduction of the pain threshold that facilitates the onset of every new attack leading to chronicization

Integrated Spectroscopy of Bulge Globular Clusters and Fields. II. Implications for stellar population models and elliptical galaxies

Synthetic Lick indices (e.g. Mg_2, Fe, etc.) of Simple Stellar Population (SSP) models are calibrated for the first time up to solar metallicity with a sample of Milky Way globular clusters (GCs) which includes the metal rich GCs of the Galactic bulge. This metallicity range is relevant to elliptical galaxies. It is shown that the Bulge GCs and integrated light follow the same correlation between Mg and Fe indices of elliptical galaxies, showing weaker Fe indices at given Mg indices with respect to models that assume solar-scaled abundances. This similarity is the robust empirical evidence for enhanced alpha/Fe ratios in the stellar populations of elliptical galaxies, since the globular clusters are independently known to be alpha-enhanced. The uniqueness of this alpha-overabundance solution is checked by exploring the whole range of model ingredients. We argue that the standard models reproduce the Mg-Fe correlation at low metallicities because the stellar templates used in the synthesis are the alpha-enhanced stars of the galactic Halo. These same models, however, fail to recover the Mg-Fe pattern of Bulge clusters and ellipticals at high metallicities because the high-metallicity templates are disk stars, which are not alpha-enhanced. The new SSP models by Thomas, Maraston & Bender (2002) which incorporate the dependence on alpha/Fe reproduce the Mg and Fe indices of GCs at all metallicities, with alpha/Fe=+0.3, which is in agreement with spectroscopic abundance determinations. The Balmer indices (Hbeta, Hdelta, Hgamma) are very well calibrated, provided the Horizontal Branch morphology is taken into account. In particular, we reproduce the Balmer lines of NGC 6388 and NGC 6441, which are metal-rich GCs with a tail of warm Horizontal Branch stars. {Abridged}Comment: 19 pages, 13 figures, Astronomy and Astrophysics in press. Only minor changes after the referee repor

Do emotional difficulties and peer problems hew together from childhood to adolescence? The case of children with a history of developmental language disorder (DLD)

Children and adolescents with developmental language disorder (DLD) are, overall, vulnerable to difficulties in emotional adjustment and in peer relations. However, previous research has shown that different subgroups follow different trajectories in respect of quality of peer relations. Less is known of the trajectories of emotional development. We consider here the possibility that development in these two domains is interrelated: that is, the trajectories of emotional and peer problems will proceed in parallel. We conducted longitudinal joint trajectories analyses of emotional and peer relations in a sample of young people identified as having DLD at age 7 years and seen at intervals up to 16 years. Potential influences on joint trajectory group membership were examined. Findings revealed five distinct joint trajectories. Emotional and peer difficulties do hew together from childhood to adolescence for just over half of the sample, but not all. The variables most clearly associated with group membership were pragmatic language ability, prosociality and parental mental health. This is the first study to examine joint longitudinal trajectories of emotional and peer difficulties in individuals with DLD. We demonstrate that development in individuals with DLD is heterogeneous and identify three key variables associated with personal and social adjustment from childhood to adolescence. Theoretical and clinical implications of these findings are discussed

Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer

The use of trastuzumab, a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) alteration present in 25 to 30% of breast cancers, has been associated with improved survival outcomes in both the adjuvant and metastatic settings. However, despite the robust clinical efficacy of trastuzumab in HER2-positive metastatic breast cancer (MBC), primary and secondary resistance remains a clinical challenge. Although lapatinib has demonstrated modest activity in this setting, trials reported to date have yet to demonstrate improvements in overall survival with its use. Novel therapeutic strategies to circumvent trastuzumab resistance are warranted, and agents targeting the HER, vascular endothelial growth factor, heat shock protein 90, phosphoinositide 3 kinase/Akt/mammalian target of rapamycin, and insulin-like growth factor-1 receptor pathways represent rational approaches in the management of HER2-positive disease. In this review, early-phase and emerging trial data surrounding the use of these promising agents in HER2-positive MBC will be discussed

A wide-field photometric study of the globular cluster system of NGC 4636

We investigate the unusually rich cluster system of NGC4636 with wide-field Washington photometry. The globular cluster luminosity function can be followed roughly 1 mag beyond the turn-over magnitude. This corresponds to a distance modulus of m-M=31.24+-0.17, 0.4 mag larger than the distance determined from surface brightness fluctuations. The high specific frequency is confirmed, yet the exact value remains uncertain because of the uncertain distance: it varies between 5.6+-1.2 and 8.9+-1.2. The globular cluster system has a clearly bimodal color distribution. The color peak positions show no radial dependence and are in good agreement with the values found for other galaxies studied in the same filter system. However, a luminosity dependence is found: brighter clusters with an ``intermediate'' color exist. The clusters exhibit a shallow radial distribution within 7'.Within the same radial interval, the galaxy light has a distinctly steeper profile. Because of the difference in the cluster and light distribution the specific frequency increases considerably with radius. At 7' and 9' the density profiles of the red and blue clusters, respectively, change strongly which indicates that we reach the outer rim of the cluster system at approximately 11'. This feature is seen for the first time in a globular cluster system. While the radial distribution of the cluster and field populations are rather different, this is not true for the ellipticity of the system: the elongation as well as the position angle of the cluster system agree well with the galaxy light. We compare the radial distribution of globular clusters with the light profiles for a sample of elliptical galaxies. The difference observed in NGC 4636 is typical of an elliptical galaxy of this luminosity.Comment: Accepted for publication in A&A, 16 pages, 15 figure