Annals of the New York Academy of Sciences
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Primary brain tumors account for less than 2% of all cancers in adults; however, they are often associated with neurologic morbidity and high mortality. Glioblastoma multiforme (GBM) has been a focus of new therapy development in neurooncology because it is the most common primary brain tumor in adults. Standard-of-care therapy for newly diagnosed GBM includes surgical resection, radiotherapy, and temozolomide, administered both during and after radiotherapy. ⋯ Nonetheless, first-generation targeted agents have failed to demonstrate survival benefits in unselected GBM patient populations. Several mechanisms of treatment failure of the first-generation designer drugs have been proposed, whereas new strategies have been developed to increase effectiveness of these agents. Here we will discuss the recent development and the strategies to optimize the effectiveness of designer therapy for GBM.
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Cancer pain is prevalent and often multifactorial. For a segment of the cancer pain population, pain control remains inadequate despite full compliance with the WHO analgesic guidelines including use of co-analgesics. The failure to obtain acceptable pain or symptom relief prompted the inclusion of a fourth step to the WHO analgesic ladder, which includes advanced interventional approaches. ⋯ There are several sites for neurolytic blockade of the sympathetic nervous system for the treatment of cancer pain. The more common sites include the celiac plexus, superior hypogastric plexus, and ganglion impar. Today, interventional pain-relieving approaches should be considered a critical component of a multifaceted therapeutic program of cancer pain relief.
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Ann. N. Y. Acad. Sci. · Apr 2008
ReviewEndometriosis and infertility: epidemiology and evidence-based treatments.
Endometriosis is an estrogen-dependent disorder defined as the presence of endometrial tissue outside of the uterine cavity. A leading cause of infertility, endometriosis has a prevalence of 0.5-5% in fertile and 25-40% in infertile women. The optimal choice of management for endometriosis-associated infertility remains obscure. ⋯ Controlled ovarian hyperstimulation with intrauterine insemination is recommended in early-stage and surgically corrected endometriosis when pelvic anatomy is normal. In advanced cases, in vitro fertilization is a treatment of choice, and its success may be augmented with prolonged gonadotropin-releasing hormone analog treatment. Further randomized clinical trials focusing on diverse etiopathogenic mechanisms and therapeutic innovation are necessary to find more conclusive, evidence-based answers regarding this enigmatic disease.
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Ann. N. Y. Acad. Sci. · Mar 2008
ReviewThe brain's default network: anatomy, function, and relevance to disease.
Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. ⋯ These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
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Lymphangioleiomyomatosis (LAM) is a rare, multisystem disease affecting primarily premenopausal women. The disease is characterized by cystic lung disease, at times leading to respiratory compromise, abdominal tumors (in particular, renal angiomyolipomas), and involvement of the axial lymphatics (e.g., adenopathy, lymphangioleiomyomas). Disease results from the proliferation of neoplastic cells (LAM cells), which, in many cases, have a smooth muscle cell phenotype, express melanoma antigens, and have mutations in one of the tuberous sclerosis complex genes (TSC1 or TSC2). ⋯ Lymphatic channels, expressing characteristic lymphatic endothelial cell markers, are found within the LAM lung nodules. LAM cells may also be localized within the walls of the axial lymphatics, and, in some cases, penetrate the wall and proliferate in the surrounding adipose tissue. Consistent with extensive lymphatic involvement in LAM, the serum concentration of VEGF-D, a lymphangiogenic factor, is higher in LAM patients than in healthy volunteers.