Utilisation des toxines botuliniques pour soulager la douleur réfractaire et d’autres symptômes du parkinsonisme

Background: Parkinson's disease (PD) and other parkinsonian syndromes are chronic, progressive neurodegenerative diseases. With advancing disease, both motor and non-motor symptoms represent a considerable burden and symptom relief and quality of life improvement become the main goal of treatment. Botulinum toxins (BTX) are an effective treatment modality for many neurological conditions. Methods: To understand the potential usefulness of BTX in this population, we performed a retrospective chart review of all patients with a clinical diagnosis of idiopathic PD and atypical parkinsonism who received treatment with BTX injections in our center from 1995 to 2014 for a variety of symptoms. Response to BTX was assessed using a subjective Clinical Global Impression. Results: Records of 160 patients were reviewed. Probable idiopathic PD was the diagnosis in 117 patients (73.1%). The main indication for BTX treatment was pain (50.6% of cases). Other indications were the treatment of functional impairment resulting from dystonia (26.25%), sialorrhea (18.75%), freezing of gait, and camptocormia. Considering pain as indication, 81% of all patients with PD reported benefits after the first BTX injections. This benefit was maintained after the last recorded visit without significant difference in outcome compared with the first injection (p=0.067). Similar results were observed in patients with atypical parkinsonism. Conclusions: Our results confirm the safety and efficacy of different uses of BTX in the symptomatic treatment of patients with parkinsonism even in advanced stages of the disease, and suggest BTX treatment could have a safe and useful role in the treatment of pain in this population.Contexte: La maladie de Parkinson (MP) et les divers syndromes parkinsoniens sont des affections neuro-dégénératives chroniques et évolutives. Avec la progression de la maladie, tant ses symptômes moteurs que ses symptômes non-moteurs finissent par représenter un fardeau considérable. Le soulagement de ces symptômes et l’amélioration de la qualité de vie des patients deviennent alors le principal objectif d’un traitement. À cet égard, les toxines botuliniques (« BTX ») demeurent une modalité de traitement efficace dans le cas de nombreux troubles neurologiques. Méthodes: Afin de comprendre l’utilité potentielle des toxines botuliniques, nous avons procédé à un examen rétrospectif des dossiers de tous les patients qui, après avoir reçu un diagnostic de MP idiopathique et de syndrome parkinsonien atypique, ont bénéficié dans notre centre, de 1995 à 2014, d’un traitement par injection de toxines botuliniques pour toute une gamme de symptômes. La réponse à ces toxines a ensuite été évaluée au moyen de l’échelle Clinical Global Impression. Résultats: Nous avons passé en revue les dossiers de 160 patients. Des cas probables de MP idiopathiques ont été diagnostiqués chez 117 patients (73,1 %). Fait à noter, le soulagement de la douleur était le principal motif justifiant un traitement par injection de toxines botuliniques (50,6 % des cas). D’autres motifs étaient avancés : traiter un handicap fonctionnel résultant de la dystonie (26,25 %), la sialorrhée (18,75 %), des blocages (freezing of gait) et la camptocormie. Si l’on s’en tient à la douleur, 81 % des patients atteints de la MP ont signalé des bienfaits à la suite des premières injections de toxines botuliniques. Ces bienfaits ont perduré après leur dernière visite attestée, et ce, sans qu’on ait observé de différences significatives dans les résultats par rapport à la première injection (p = 0,067). Des résultats identiques ont été constatés chez des patients atteints d’un syndrome parkinsonien atypique. Conclusions: Nos résultats confirment à la fois la sécurité et l’efficacité des différents usages des toxines botuliniques dans le soulagement, même à un stade avancé, des symptômes de patients atteints de parkinsonisme. Ils suggèrent aussi qu’un traitement par injection de toxines botuliniques pourrait, sans danger, jouer un rôle utile dans le traitement de la douleur éprouvée par cette catégorie de patients.Fil: Bruno, Veronica Andrea. University Health Network. Toronto Western Hospital; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fox, Susan H.. University Health Network. Toronto Western Hospital; CanadáFil: Mancini, Deborah. University Health Network. Toronto Western Hospital; CanadáFil: Miyasaki, Janis M.. University of Alberta; Canad

Palliative care and Parkinson's disease : meeting summary and recommendations for clinical research

Introduction: Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinson’s disease (PD) and outpatient palliative care services are now offered by several movement disorders centers. Methods: An International Working Group Meeting on PD and Palliative Care supported by the Parkinson’s Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice. Results: Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research. Conclusions: Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers

Prognostic predictors relevant to end-of-life palliative care in Parkinson's disease and related disorders: A systematic review

Parkinson's disease and related disorders (PDRD) are the second most common neurodegenerative disease and a leading cause of death. However, patients with PDRD receive less end-of-life palliative care (hospice) than other illnesses, including other neurologic illnesses. Identification of predictors of PDRD mortality may aid in increasing appropriate and timely referrals. To systematically review the literature for causes of death and predictors of mortality in PDRD to provide guidance regarding hospice/end-of-life palliative care referrals. We searched MEDLINE, PubMed, EMBASE and CINAHL databases (1970-2020) of original quantitative research using patient-level, provider-level or caregiver-level data from medical records, administrative data or survey responses associated with mortality, prognosis or cause of death in PDRD. Findings were reviewed by an International Working Group on PD and Palliative Care supported by the Parkinson's Foundation. Of 1183 research articles, 42 studies met our inclusion criteria. We found four main domains of factors associated with mortality in PDRD: (1) demographic and clinical markers (age, sex, body mass index and comorbid illnesses), (2) motor dysfunction and global disability, (3) falls and infections and (4) non-motor symptoms. We provide suggestions for consideration of timing of hospice/end-of-life palliative care referrals. Several clinical features of advancing disease may be useful in triggering end-of-life palliative/hospice referral. Prognostic studies focused on identifying when people with PDRD are nearing their final months of life are limited. There is further need for research in this area as well as policies that support need-based palliative care for the duration of PDRD

Associação de medroxiprogesterona ao protocolo Ovsynch para inseminação artificial em tempo fixo de búfalas cíclicas (Bubalus bubalis) criadas na Amazônia Oriental.

O presente estudo visou avaliar os efeitos da associação da medroxiprogesterona (análogo sintético da progesterona) ao protocolo Ovsynch sobre o crescimento folicular, a ovulação e a taxa de concepção de búfalas criadas na Amazônia Oriental (Tracuateua-PA). Vinte e sete fêmeas adultas (G1 n=14 e G2 n=13), cíclicas, sem bezerro ao pé e com ECC 3,5 foram submetidas a Ovsynch. Os animais do G2 receberam 60 mg de medroxiprogesterona entre D0 e D7 (D0=início do tratamento). A ultra-sonografia ovariana foi realizada nos D 0, 7, 9 e 10. O contingente de folículos pequenos diferiu no D7 (G1: 4,57±0,60 versus G2: 6,54±0,67; P=0,05). Tempo e tratamento influenciaram o diâmetro folicular no D7. O crescimento do folículo dominante entre D7 e D9 foi maior nos animais tratados (G1: 2,05±0,49 mm/dia versus 3,48±0,41 mm/dia; P0,05). Os achados sugerem que a medroxiprogesterona (1) aumenta recrutamento folicular e retarda o crescimento dos folículos com diâmetro maior que 5,0 mm entre D0 e D7; (2) sua retirada incrementa em 1,7 vezes o crescimento folicular do D7 ao D9; (3) pode contribuir para a ovulação de folículos maiores e, em tese, para maior formação de tecido luteínico; (4) não promove ovulação precoce após o Ovsynch; (5) não eleva as taxas de concepção após sincronização de fêmeas cíclicas e com bom escore corporal, devendo ser avaliada para uso em fêmeas acíclicas ou com ECC mais baixo.Disponível também on-line

Physical Models for Accreting Pulsars at High Luminosity

A new window for better understanding the accretion onto strongly magnetized neutron stars in X-ray binaries is opening. In these systems the accreted material follows the magnetic field lines as it approaches the neutron star, forming accretion columns above the magnetic poles. The plasma falls toward the neutron star surface at near-relativistic speeds, losing energy by emitting X-rays. The X-ray spectral continua are commonly described using phenomenological models, i.e., power laws with different types of curved cut-offs at higher energies. Here we consider high luminosity pulsars. In these systems the mass transfer rate is high enough that the accreting plasma is thought to be decelerated in a radiation-dominated radiative shock in the accretion columns. While the theory of the emission from such shocks had already been developed by 2007, a model for direct comparison with X-ray continuum spectra in xspec or isis has only recently become available. Here we analyze the broadband X-ray spectra of the accreting pulsars Centaurus X-3 and 4U1626-67 obtained withNuSTAR. We present results from traditional empirical modeling as well as successfully apply the radiation-dominated radiative shock model. We also fit the energy-dependent pulse profiles of 4U 1626-67 using a new relativistic light bending model

Phytochemical, toxicity and microbiological activity study of tynanthus micranthus corr : (Mello ex Schum: Bignoniaceae)

Tynanthus micranthus, a plant species belonging to family Bignoniaceae, is widely used on the northwest region of Paraná state as stimulant and aphrodisiac. The lack of studies about this specie motivated the research for phytochemical evaluation and some biological activities of the plant. Toxicity studies of the ethanolic extracts and fractions of the species investigated were performed in Artemia salina eggs in addition to antimicrobial activity of the ethanolic extracts against species of some bacteria strains. The results indicated the presence of β-sitosterol steroid in the hexane fraction and apigenin flavone in the chloroform fraction, both isolated from the stalk. Some fractions developed toxicity over Artemia salina and its extracts showed to be lethal causing death of certain bacterial strains.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Occurrence of L-iduronic acid and putative D-glucuronyl C5-epimerases in prokaryotes

Glycosaminoglycans (GAGs) are polysaccharides that are typically present in a wide diversity of animal tissue. Most common GAGs are well-characterized and pharmaceutical applications exist for many of these compounds, e.g. heparin and hyaluronan. In addition, also bacterial glycosaminoglycan-like structures exist. Some of these bacterial GAGs have been characterized, but until now no bacterial GAG has been found that possesses the modifications that are characteristic for many of the animal GAGs such as sulfation and C5-epimerization. Nevertheless, the latter conversion may also occur in bacterial and archaeal GAGs, as some prokaryotic polysaccharides have been demonstrated to contain L-iduronic acid. However, experimental evidence for the enzymatic synthesis of L-iduronic acid in prokaryotes is as yet lacking. We therefore performed an in silico screen for D-glucuronyl C5-epimerases in prokaryotes. Multiple candidate C5-epimerases were found, suggesting that many more microorganisms are likely to exist possessing an L-iduronic acid residue as constituent of their cell wall polysaccharides

How integrated are neurology and palliative care services? Results of a multicentre mapping exercise

Background: Patients affected by progressive long-term neurological conditions might benefit from specialist palliative care involvement. However, little is known on how neurology and specialist palliative care services interact. This study aimed to map the current level of connections and integration between these services. Methods: The mapping exercise was conducted in eight centres with neurology and palliative care services in the United Kingdom. The data were provided by the respective neurology and specialist palliative care teams. Questions focused on: i) catchment and population served; ii) service provision and staffing; iii) integration and relationships. Results: Centres varied in size of catchment areas (39-5,840 square miles) and population served (142,000-3,500,000). Neurology and specialist palliative care were often not co-terminus. Service provisions for neurology and specialist palliative care were also varied. For example, neurology services varied in the number and type of provided clinics and palliative care services in the settings they work in. Integration was most developed in Motor Neuron Disease (MND), e.g., joint meetings were often held, followed by Parkinsonism (made up of Parkinson’s Disease (PD), Multiple-System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP), with integration being more developed for MSA and PSP) and least in Multiple Sclerosis (MS), e.g., most sites had no formal links. The number of neurology patients per annum receiving specialist palliative care reflected these differences in integration (range: 9–88 MND, 3–25 Parkinsonism, and 0–5 MS). Conclusions: This mapping exercise showed heterogeneity in service provision and integration between neurology and specialist palliative care services, which varied not only between sites but also between diseases. This highlights the need and opportunities for improved models of integration, which should be rigorously tested for effectiveness