Parkinson's Disease-Mild Cognitive Impairment (PD-MCI): A Useful Summary of Update Knowledge.

Mild cognitive impairment (MCI) is a common feature in Parkinson's Disease (PD), even at the time of diagnosis. Some levels of heterogeneity in nature and severity of cognitive impairment and risk of conversion to Parkinson's Disease Dementia (PDD) exist. This brief overview summarized the current understanding of MCI in PD, by considering the following major points: historical development of the clinical entity, evaluation, epidemiology, predictors and outcomes, neuroimaging findings, pathophysiology, treatment, and pharmacological and non-pharmacological intervention. MCI in PD represents a concept in evolution and plays a pivotal role in advancing our understanding of the disease mechanisms, with the ultimate goal of building effective strategies to prevent conversion into PDD. Challenges for future research are also discussed.

Propranolol in the management of infantile hemangiomas: clinical response and predictors.

BACKGROUND: Recent data suggest that propranolol is an effective treatment for infantile hemangiomas (IHs). Data on the optimal dose, duration of therapy, and predictors of response are currently lacking. OBJECTIVE: To assess the clinical response to and predictors of propranolol use in the treatment of IH. METHODS: Retrospective cohort study of 44 patients. Two independent assessors evaluated improvement by comparing serial digital photographs using a 100 mm visual analogue scale (VAS), where 5 mm change represented 10% change in the size or appearance of the IH. RESULTS: Propranolol was started at a mean age of 7.8 (SD 8.21) months and was used for 7.3 (SD 4.8) months before weaning. The mean percent improvement compared to baseline (as measured by the VAS) was 78% (SD 23%). Minor adverse events were noted in 32% of patients. The most significant predictor of regrowth after weaning was a IH > 5 cm in size (p  =  .017). CONCLUSIONS: Propranolol is effective in IH, but the side effects and the possibility of regrowth should be considered.

Primitive myxoid mesenchymal tumor of infancy in a preterm infant.

Primitive myxoid mesenchymal tumor of infancy is a recently recognized entity that has been added to the differential diagnosis of myxoid tumors of the soft tissue. Few cases have been reported of this entity in the literature, but none presenting in a preterm infant. We present the case and clinical course of a preterm boy with a primitive myxoid mesenchymal tumor of infancy that occurred following excision of a congenital juvenile xanthogranuloma.

A locally active antiinflammatory macrolide (MLD987) for inhalation therapy of asthma.

One of the characteristic features of asthma is a persistent pulmonary inflammation, with increased numbers of eosinophils and activated T-lymphocytes in the airways. T-helper cells of the Th2 phenotype play a pivotal role in the pathogenesis of asthma, and they are believed to orchestrate the asthmatic response by releasing a wide repertoire of cytokines. Herein, we describe the design, synthesis, and evaluation in models of allergic asthma of a locally active T-cell modulator, MLD987 (1). Compound 1 is a potent immunosuppressant that inhibits the activation, proliferation, and release of cytokines from T-cells with IC(50) values in the low nanomolar range. In a Brown-Norway rat model of allergic asthma, 1, when given into the airways by intratracheal administration (ED(50) = 1 mg/kg) or by inhalation (ED(50) = 0.4 mg/kg), potently reduced the influx of leukocytes into bronchoalveolar lavage fluid samples obtained from antigen-challenged animals. In contrast, 1 had an appreciably weaker activity in this model when given orally or intravenously. Pharmacokinetic evaluation in rat and rhesus monkey showed that 1 had both a low oral (2-4%) and a low pulmonary (7%, monkey) bioavailability. These findings are consistent with a local site of action of the compound and rule out that its antiinflammatory activity in the lung was caused by systemically absorbed material, which had been swallowed during inhalation or which had entered the circulation via the airways. Local administration and the metabolically soft structure of 1, which favors rapid systemic metabolism to less immunosuppressive metabolite 2, are the main reasons for the low exposure and weak systemic activity of the compound. Administration of a locally active compound such as 1, by inhalation, should reduce systemic side effects. Our results indicate that 1 has the potential to serve as an alternative to inhaled glucocorticosteroids for the long-term therapy of asthma of all grades of severity.