Citations

AbstractBackgroundThe Cognitive and Emotional Health Project (CEHP) seeks to identify the demographic, social, and biological determinants of cognitive and emotional health in the older adult. As part of the CEHP, a critical evaluation study committee was formed to assess the state of epidemiological research on demographic, social, and biological determinants of cognitive and emotional health.MethodsCriteria for inclusion in the survey were large cohort studies, longitudinal in design, participants predominantly 65 years or older, with measurements of both cognition and emotion, and information on a wide variety of demographic, psychosocial, and biological factors. North American and European studies, which met these criteria, were selected for the review. Outcome measures included cognition, cognitive decline, and cognitive function. For emotion, symptoms included depression and anxiety, positive and negative affect, subjective well being, mastery, and resilience.ResultsNinety‐six papers were identified that addressed cognitive and emotional outcomes. A large variety of risk factors were consistently identified with cognitive outcomes, particularly those previously associated with increased risk of cardiovascular disease. There was considerable overlap between risk factors for cognitive and emotional outcomes.ConclusionThis review identifies a large number of lifestyle and health behaviors that alter the risk for maintenance of cognitive and emotional health. Large longitudinal cohort studies are a unique source to explore factors associated with cognitive and emotional health. Secondary analyses of these studies should be encouraged as should the development of standardized questionnaires to measure cognitive and emotional health. Future research in this field should study cognitive and emotional health simultaneously.

While “sinus” headache is a widely accepted clinical diagnosis, many medical specialists consider it to be an uncommon cause of recurrent headaches. Unnecessary diagnostic studies, surgical interventions, and medical treatments are often the result of the inappropriate diagnosis of sinus headache. Both the International Headache Society and the American Academy of Otolaryngology–Head and Neck Surgery have attempted to characterize conditions leading to headaches of rhinogenic origin. However, they have done so from different perspectives and in isolation from the other specialty groups. An interdisciplinary ad hoc committee recently convened to discuss the role of sinus disease and the nose in the etiology of headache and to review recent epidemiologic studies suggesting that sinus headache (headache of rhinogenic origin) and migraine are frequently confused with one another. Clinical trial data are presented which clearly indicate that the majority of sinus headaches can actually be classified as migraines. This committee reviewed scientific evidence available from multiple disciplines and concludes that considerable research and clinical study are needed to further understand and explain the role of nasal pathology and autonomic activation in migraine and headaches of rhinogenic origin. However, there was a consensus from this group that greater diagnostic and therapeutic attention needs to be given to patients complaining of sinus headache that may indeed be due to the nose.

Abstract The term “bronchiolitis” refers to a broad morphologic spectrum of inflammatory events that are centered on small conducting airways. Bronchiolitis may be an isolated pathologic finding, although it is often a secondary consequence of diseases affecting other parts of the conducting apparatus or pulmonary acinus. Divergent causes of bronchiolitis may have similar microscopic findings. Hence, a pathologic diagnosis is nonspecific and not clinically meaningful unless placed in the context of relevant clinical and radiographic findings. Etiologically, most cases of bronchiolitis are infectious in nature or related to smoking. Increasingly, other causes of bronchiolitis have been recognized, including collagen vascular disease, idiopathic inflammatory bowel disease, or toxins/drugs. Many cases are idiopathic. Histologically, most examples of bronchiolitis demonstrate acute inflammation, usually corresponding to viral infection. Other well-defined histologic categories of bronchiolitis include bronchiolitis obliterans, in which there is fibroblast proliferation within airspaces, and follicular bronchiolitis, corresponding to lymphoid hyperplasia with formation of germinal centers. In recent years, several new forms of bronchiolitis have been recognized, including constrictive bronchiolitis, diffuse panbronchiolitis, and airway-centered fibrosis. This article highlights the clinical and pathologic features of these more recently described entities.

Abstract A flurry of articles on the structure of different domains of BRCA1 and BRCA2 have not only shed light on the biology of these proteins but have also raised hopes that these data could eventually be used to infer cancer association for a large number of inherited missense mutations whose effect on protein function is unclear. (Cancer Res 2006; 66(4): 1897-9)

AbstractMetastatic renal cell carcinoma (RCC) is an aggressive disease refractory to most existing therapeutic modalities. Identifying new markers for disease progression and drug targets for RCC will benefit this unmet medical need. We report a subset of clear cell and papillary cell RCC aberrantly expressing the lymphocyte activation marker CD70, a member of the tumor necrosis factor superfamily. Importantly, CD70 expression was found to be maintained at the metastatic sites of RCC. Anti-CD70 antibody-drug conjugates (ADC) consisting of auristatin phenylalanine phenylenediamine (AFP) or monomethyl auristatin phenylalanine (MMAF), two novel derivatives of the anti-tubulin agent auristatin, mediated potent antigen-dependent cytotoxicity in CD70-expressing RCC cells. Cytotoxic activity of these anti-CD70 ADCs was associated with their internalization and subcellular trafficking through the endosomal-lysosomal pathway, disruption of cellular microtubule network, and G2-M phase cell cycle arrest. The efficiency of drug delivery using anti-CD70 as vehicle was illustrated by the much enhanced cytotoxicity of antibody-conjugated MMAF compared with free MMAF. Hence, ADCs targeted to CD70 can selectively recognize RCC, internalize, and reach the appropriate subcellular compartment(s) for drug release and tumor cell killing. In vitro cytotoxicity of these ADCs was confirmed in xenograft models using RCC cell lines. Our findings provide evidence that CD70 is an attractive target for antibody-based therapeutics against metastatic RCC and suggest that anti-CD70 ADCs can provide a new treatment approach for advanced RCC patients who currently have no chemotherapeutic options. (Cancer Res 2006; 66(4): 2328-37)