ABSTRACT
Control of breast-to-brain metastasis remains an urgent unmet clinical need. While chemotherapies are essential in reducing systemic tumor burden, they have been shown to promote non-brain metastatic invasiveness and drug-driven neurocognitive deficits through the formation of neurofibrillary tangles (NFT), independently. Now, in this study, we investigated the effect of chemotherapy on brain metastatic progression and promoting tumor-mediated NFT. Results show chemotherapies increase brain-barrier permeability and facilitate enhanced tumor infiltration, particularly through the blood-cerebrospinal fluid barrier (BCSFB). This is attributed to increased expression of matrix metalloproteinase 9 (MMP9) which, in turn, mediates loss of Claudin-6 within the choroid plexus cells of the BCSFB. Importantly, increased MMP9 activity in the choroid epithelium following chemotherapy results in cleavage and release of Tau from breast cancer cells. This cleaved Tau forms tumor-derived NFT that further destabilize the BCSFB. Our results underline for the first time the importance of the BCSFB as a vulnerable point of entry for brain-seeking tumor cells post-chemotherapy and indicate that tumor cells themselves contribute to Alzheimer's-like tauopathy.
Subject(s)
Alzheimer Disease , Brain Neoplasms , Breast Neoplasms , Humans , Female , Matrix Metalloproteinase 9/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Brain/metabolism , Brain Neoplasms/drug therapy , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolismABSTRACT
La drepanocytose dans sa forme majeure; est caracterisee par la survenue frequente de crises douloureuses a repetition. La bonne qualite de la gestion medicale de ces crises est un gage du confort de vie du drepanocytaire. Les niveaux de prise en charge des malades et la qualite de la gestion des crises drepanocytaires sont peu etudies en Afrique. Cette etude avait pour objectifs de preciser ces deux parametres auMali.Apres analyse des donnees recueillies par l'interrogatoire sur une fiche d'enquete individuelle testee et validee; l'etude a permis de constater que la crise drepanocytaire etait geree a tous les niveaux de reference de la pyramide sanitaire du Mali par un personnel de plusieurs niveaux de qualification. La gestion de cette crise n'obeissait pas a un schema unique. Parmi lesmedications prescrites; les vasodilatateurs occupaient la premiere place. Les antalgiques majeurs etaient prescrits par moins de 10des agents de sante enquetes. La transfusion sanguine apparaissait comme une therapeutique trop souvent prescrite. Les strategies d'amelioration de la prise en charge de la crise drepanocytaire au Mali doivent prendre en compte l'urgence de la mise en place des programmes de formation et de recyclage des agents de sante aux schemas standards d'efficacite prouvee
Subject(s)
Anemia, Sickle Cell , Medical StaffABSTRACT
The most common form of sickle cell disease is characterized by frequently recurring pain crises. Success in managing these crises can be considered a measure of the quality of life in patients with sickle cell disease. There is a paucity of data on the level of care and quality of management of pain crises in sickle cell patients in Africa. The purpose of this study was to assess these two parameters in Mali. Data were collected by interview using a validated individual survey form. Analysis of data demonstrated that sickle cell crises were being managed at all levels of the health care system by practitioners with differing competency levels. Management did not follow a single algorithm. Vasodilators were the most commonly prescribed medications. Major analgesics were prescribed by fewer than 10% of the practitioners surveyed. Blood transfusion appeared to be overused. Based on these findings we conclude that strategies to improve management of sickle cell pain crises must recognize the urgent need for training health care providers to use standardized algorithms of proven efficacy.
Subject(s)
Anemia, Sickle Cell/complications , Pain Management , Pain/etiology , Female , Health Personnel , Humans , Male , Mali , Prospective StudiesABSTRACT
La drepanocytose est une maladie genetique qui; dans sa forme grave; affecte 1 a 3p.100 des naissances au Mali. Cette forme est caracterisee chez le malade; par la survenue frequente de crises drepanocytaires. La qualite de la gestion medicale de ces crises est un gage du confort de vie du drepanocytaire. L'objectif de cette etude etait d'etudier la qualite de la gestion de la crise drepanocytaire par les agents de sante au Mali. Pour ce faire; nous avons conduit une etude de sondage; prospective et descriptive a l'aide d'un questionnaire destine aux agents de sante de tous les niveaux de qualification de decembre 2001 a octobre 2002. Les resultats de cette etude laissent apparaitre que la crise drepanocytaire est geree a tous les niveaux de reference de la pyramide sanitaire. Cette gestion est assuree par un personnel dont les niveaux de qualification sont differents ; incluant medecins specialises ou non et non medecins. La gestion de la crise n'obeit pas a un schema unique. Quelque soit le niveau de qualification du prescripteur; les medications prescrites comportent dans une proportion significative de cas; des medicaments dont l'efficacite dans la gestion de la crise drepanocytaire n'est pas documentee ou qui pourraient soumettre le malade a un risque de complication iatrogene. Parmi ces medicaments les vasodilatateurs occupent la premiere place. Le tres faible taux de prescription des antalgiques majeurs autorise a penser que la gestion de la douleur chez le drepanocytaire est insuffisante. Nous concluons que la qualite de la gestion de la crise drepanocytaire par les agents de sante est insuffisante a tous les niveaux de reference de la pyramide sanitaire au Mali
Subject(s)
Anemia, Sickle Cell , Health Care SurveysABSTRACT
BACKGROUND: Conventional wisdom holds that multiple-day samples should not be obtained with the Rotorod Sampler because sampling efficiency declines over long sampling periods such as weekends. OBJECTIVE: The purpose of this present investigation was to test this position under experimental conditions. METHODS: Atmospheric pollen samples were collected over 24-hour, 48-hour, and 72-hour periods by five Rotorod Samplers operated in a compact sampling array. Pollen counts obtained from the latter two sampling periods were compared with corresponding values computed from 24-hour samples. Differences in pollen recovery were assessed using Pearson's correlation coefficient and paired comparisons t-tests. RESULTS: Two hundred seventeen atmospheric samples were obtained between March 30 and October 8, 1998. Differences between the 48-hour and 72-hour samples and their computed counterparts were not statistically significant when the atmospheric pollen concentration was less than 100 pollen grains per cubic meter of air (p/m3). At higher pollen concentrations large quantitative and statistically significant differences were noted. CONCLUSIONS: These data suggest that particle loading on Rotorod collector rods caused sample quality to deteriorate when atmospheric pollen concentrations exceed 100 p/m3. Multiple-day sampling periods appear to be justified when the atmospheric pollen concentration is less than this threshold. Adjusting the Rotorod Sampler's duty cycle may offer a means to collect samples over periods longer than 24 hours during times of the year when pollen shed is heavy.
Subject(s)
Air Pollution/analysis , Pollen/cytology , Cell Count , Methods , Sample Size , Seasons , Time FactorsABSTRACT
OBJECTIVE: In this investigation we sought to summarize the atmospheric surveys that were published in two United States allergy journals (and subsequent series) during a 31-year period beginning in 1966. DATA SOURCES: All original articles published in the Annals of Allergy (and its subsequent series) and the Journal of Allergy (and its subsequent series) were cataloged in a computer database beginning with the first issues of 1966. Publications were classified in a manner reflecting their aerobiologic content. STUDY SELECTION: From this database of articles (n = 7,403), atmospheric surveys for pollen, spores, and other aeroflora were identified and summarized according to standard criteria. For each study we documented the sampling instruments used, the height of these instruments off of the ground, the study period, and the sampling schedule. RESULTS: Sixty-one atmospheric surveys were summarized: 30 from locations in the United States and 31 from outside of the country. Various volumetric and nonvolumetric samplers were used; the height of instruments above the ground and the sampling protocols varied widely. CONCLUSIONS: This investigation can serve as a companion to earlier compilations. These data should prove more useful than information available via electronic and paper indexes.
