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81.
Mestron A Webb SM Astorga R Benito P Catala M Gaztambide S Gomez JM Halperin I Lucas-Morante T Moreno B Obiols G de Pablos P Paramo C Pico A Torres E Varela C Vazquez JA Zamora J Albareda M Gilabert M 《European journal of endocrinology / European Federation of Endocrine Societies》2004,151(4):439-446
OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. METHODS: Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. RESULTS: Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable. 相似文献
82.
Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia 总被引:1,自引:1,他引:1
Robinson N; Sanders JE; Benyunes MC; Beach K; Lindgren C; Thompson JA; Appelbaum FR; Fefer A 《Blood》1996,87(4):1249-1254
Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial. 相似文献
83.
Intergenerational influences on the growth of Maya children: The effect of living conditions experienced by mothers and maternal grandmothers during their childhood
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84.
Karl Pillemer Emily K. Chen Catherine Riffin Holly Prigerson MC Reid Leslie Schultz 《American journal of public health》2015,105(11):2237-2244
We employed the research-to-practice consensus workshop (RTP; workshops held in
New York City and Tompkins County, New York, in 2013) model to merge researcher
and practitioner views of translational research priorities in palliative care.
In the RTP approach, a diverse group of frontline providers generates a research
agenda for palliative care in collaboration with researchers. We have presented
the major workshop recommendations and contrasted the practice-based research
priorities with those of previous consensus efforts. We uncovered notable
differences and found that the RTP model can produce unique insights into
research priorities. Integrating practitioner-identified needs into research
priorities for palliative care can contribute to addressing palliative care more
effectively as a public health issue.Over the past 2 decades, palliative care has become established as a promising approach
for addressing the needs of individuals with life-threatening illnesses from a holistic,
interdisciplinary perspective. For this project, we defined palliative care as an
approach that improves the quality of life of patients and families facing the problems
encountered in life-threatening illness by preventing and relieving suffering. Core
components of palliative care include providing relief from pain and other distressing
symptoms, affirming dying as a normal process, integrating psychological and spiritual
aspects of care, enhancing the quality of life of patients, and offering support systems
to patients and their families to help them live as fully as possible until death
occurs.Research suggests that palliative care results in positive patient outcomes, greater
patient and family satisfaction, and significant cost savings.1,2 The American Public Health Association, the
World Health Organization, and the Institute of Medicine3–6 have identified the
development of a robust palliative care delivery system as a key public health issue
because of the documented ability of palliative care to deliver effective and efficient
patient- and symptom-focused care to a growing population in need.In its 2013 report the American Public Health Association specifically detailed the
public health implications of palliative care, acknowledged the growing burden of
advanced chronic illness and disease in older adults, and recommended key steps to
address the problem. This policy statement called for federal, state, and local efforts
to promote effective symptom management in populations with serious illness or at the
end of life. Other recommended initiatives included the development of a palliative care
workforce, educational programs to improve uptake and use of palliative and hospice
care, and research funding to support the expansion of palliative care initiatives.
Achieving these goals will require moving beyond traditional medical practices to
include both policies and initiatives at the public health level.Despite the potential of palliative care to address the mental and physical health needs
of individuals with advanced illness, significant knowledge gaps impede its reach and
effectiveness. Reports from scientific bodies and consensus workshops have highlighted
weaknesses in the literature and called for more research on palliative care and
improved research methods.7–10 Thus, although both interest in and demand for
palliative care are increasing, reviews of the knowledge base continue to lament the
lack of research on many key issues.11,12Especially urgent is a research agenda that fits most closely with the needs of providers
who deliver palliative care. The systematic engagement of community practitioners in a
consensus process can lead to particularly useful and actionable recommendations for
research,13–15 which are greatly needed at this stage in the
development of the field. Therefore, to shed new light on research priorities in
palliative care, we used a structured, participatory method designed to solicit
practitioner input on research priorities: the research-to-practice consensus workshop
(RTP) model.16We employed the RTP approach to identify knowledge gaps and types of studies that should
be conducted to improve providers’ ability to deliver palliative care most
effectively. This model harnesses practice wisdom by engaging clinicians, agency staff,
and other practitioners with researchers in a process of articulating and refining
research questions and research priorities that honors scientific expertise and practice
wisdom. 相似文献
85.
86.
Dugan VG Varela AS Stallknecht DE Hurd CC Little SE 《Vector borne and zoonotic diseases (Larchmont, N.Y.)》2004,4(2):131-136
Although white-tailed deer (WTD; Odocoileus virginianus ) are considered the primary natural reservoir host for Ehrlichia chaffeensis, the causative agent of human monocytotropic ehrlichiosis, the potential role of other vertebrates as reservoir hosts has not been fully explored. Because domestic goats are naturally infected in areas where E. chaffeensis is endemic in deer, we evaluated the susceptibility of domestic goats to experimental infection with E. chaffeensis. A total of 12 goats were inoculated with E. chaffeensis (15B-WTD-GA or Ark strain)-infected DH82 cells by one of three routes: intravenously, subcutaneously, or intradermally. White-tailed deer simultaneously inoculated with the same dose, route, and inoculum served as positive controls; additional goats and WTD were included as negative controls. Evidence of E. chaffeensis infection was evaluated in all animals by indirect fluorescent antibody assay, PCR, and cell culture isolation techniques. All goats exposed to E. chaffeensis seroconverted by 14 days post-infection (DPI), and E. chaffeensis was isolated from one goat on 3 DPI; however, molecular or cell culture evidence of active infection was not detected in goats later than 3 DPI. White-tailed deer exhibited serologic and molecular evidence of E. chaffeensis infection throughout both trials, and E. chaffeensis was reisolated in cell culture from all infected WTD on numerous days post-infection. Our results suggest that despite the occurrence of natural infection in goats, this animal may not be susceptible to experimental infection and thus may not serve as a suitable model of E. chaffeensis reservoir host infection. 相似文献
87.
88.
89.
Juan Ramn Tejedor Clara Bueno Meritxell Vinyoles Paolo Petazzi Antonio Agraz-Doblas Isabel Cobo Raúl Torres-Ruiz Gustavo F. Bayn Raúl F. Prez Sara Lpez-Tamargo Francisco Gutierrez-Agüera Pablo Santamarina-Ojeda Manuel Ramírez-Orellana Michela Bardini Giovanni Cazzaniga Paola Ballerini Pauline Schneider Ronald W. Stam Ignacio Varela Mario F. Fraga Agustín F. Fernndez Pablo Menndez 《The Journal of clinical investigation》2021,131(13)
90.
Hunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice
Luis Varela Bernardo Stutz Jae Eun Song Jae Geun Kim Zhong-Wu Liu Xiao-Bing Gao Tamas L. Horvath 《The Journal of clinical investigation》2021,131(10)
Hypothalamic feeding circuits have been identified as having innate synaptic plasticity, mediating adaption to the changing metabolic milieu by controlling responses to feeding and obesity. However, less is known about the regulatory principles underlying the dynamic changes in agouti-related protein (AgRP) perikarya, a region crucial for gating of neural excitation and, hence, feeding. Here we show that AgRP neurons activated by food deprivation, ghrelin administration, or chemogenetics decreased their own inhibitory tone while triggering mitochondrial adaptations in neighboring astrocytes. We found that it was the inhibitory neurotransmitter GABA released by AgRP neurons that evoked this astrocytic response; this in turn resulted in increased glial ensheetment of AgRP perikarya by glial processes and increased excitability of AgRP neurons. We also identified astrocyte-derived prostaglandin E2, which directly activated — via EP2 receptors — AgRP neurons. Taken together, these observations unmasked a feed-forward, self-exciting loop in AgRP neuronal control mediated by astrocytes, a mechanism directly relevant for hunger, feeding, and overfeeding. 相似文献