Update on targeted therapies for clear cell renal cell carcinoma.

Purpose Of Review: The article reviews the evolution of targeted therapies for clear cell renal cell carcinoma (RCC) and recent developments in the field. The vast majority of work in kidney cancer deals with clear cell RCC, which is the most common variant of this malignancy. The identification of loss of function of the von Hippel-Lindau protein as the basis for clear cell RCC, in addition to the well designed clinical trials that have ensued, provide an outstanding model for the development of mechanism-based targeted therapy in cancer.

Persistence of HIV-associated cognitive impairment, inflammation, and neuronal injury in era of highly active antiretroviral treatment.

Objective: To determine whether cognitive impairment and brain injury as measured by proton magnetic resonance spectroscopy (MRS) persist in the setting of HAART.

Design: This study is an observational cohort study.

Methods: MRS was performed in 268 patients: HIV-negative controls (N = 28), HIV-positive neuroasymptomatic individuals (N = 124), and individuals with AIDS dementia complex (ADC; N = 50) on stable antiretroviral therapy (ART) with a mean duration of infection of 12 years and CD4 cell count of 309 cells/μl.

A comparison of screening batteries in the detection of neurocognitive impairment in HIV-infected Spanish speakers.

Background: A substantial number of Spanish-speaking individuals from Mexico and Central America are now living in the United States. These individuals are at heightened risk for HIV infection and, due to late diagnosis and limited resources, for HIV-associated neurocognitive disorders (HAND). Early detection is key, yet adequate methods for detecting HAND in Spanish speakers, especially in resource-poor areas, remains problematic.

Impact of genetics on the diagnosis and treatment of renal cancer.

Kidney cancer is a heterogeneous disease comprised of a number of histologic subtypes, each associated with unique genetic mutations, clinical features, and sensitivity to treatment. By examining families affected with the hereditary kidney cancer syndromes von Hippel-Lindau, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell carcinoma, and Birt-Hogg-Dubé, researchers have been able to identify the genes responsible for these syndromes. This work has revealed that kidney cancer is fundamentally a metabolic disorder, and as such, novel targeted therapies specific to their molecular biology have been developed and employed in both the hereditary and sporadic forms of renal cell carcinoma.

Cerebral metabolite abnormalities in human immunodeficiency virus are associated with cortical and subcortical volumes.

Cerebral metabolite disturbances occur among human immunodeficiency virus (HIV)-infected people, and are thought to reflect neuropathology, including proinflammatory processes, and neuronal loss. HIV-associated cortical atrophy continues to occur, though its basis is not well understood, and the relationship of cerebral metabolic disturbance to structural brain abnormalities in HIV has not been well delineated. We hypothesized that metabolite disturbances would be associated with reduced cortical and subcortical volumes.

Use of the Internet and ratings of information sources for medical decisions: results from the DECISIONS survey.

Background: The rise in Internet use for seeking health information raises questions about the role the Internet may play in how patients make medical decisions.

Objective: To examine Internet use and perceived importance of different sources of information by patients making 9 specific medical decisions covering prescription medication initiation, cancer screening, and elective surgery.

Setting: National sample of US adults identified by random-digit dialing.

Deficits and variations in patients' experience with making 9 common medical decisions: the DECISIONS survey.

Background: Although many researchers have examined patient involvement and patient-provider interactions within specific clinical environments, no nationally representative data exist to characterize patient perceptions of decision making and patient-provider communications across multiple common medical decisions.

Objective: To identify deficits and variations in the patient experience of making common medical decisions about initiation of prescription medications for hypertension, hypercholesterolemia, or depression; screening tests for colorectal, breast, or prostate cancer; and surgeries for knee or hip replacement, cataracts, or lower back pain, as well as to identify factors associated with patient confidence in the decisions.

Setting: National sample of US adults identified by random-digit dialing.

How does feeling informed relate to being informed? The DECISIONS survey.

Background: An important part of delivering high-quality, patient-centered care is making sure patients are informed about decisions regarding their health care. The objective was to examine whether patients' perceptions about how informed they were about common medical decisions are related to their ability to answer various knowledge questions.

Methods: A cross-sectional survey was conducted November 2006 to May 2007 of a national sample of US adults identified by random-digit dialing.

Patients' knowledge about 9 common health conditions: the DECISIONS survey.

Background: To make informed decisions, patients must have adequate knowledge of key decision-relevant facts.

Objective: To determine adults' knowledge about information relevant to common types of medication, screening, or surgery decisions they recently made.

Setting: National sample of US adults identified by random-digit dialing.

The Effect of Question Framing and Response Options on the Relationship between Racial Attitudes and Beliefs about Genes as Causes of Behavior.

Prior research suggests that the attribution of individual and group differences to genetic causes is correlated with prejudiced attitudes toward minority groups. Our study suggests that these findings may be due to the wording of the questions and to the choice of response options. Using a series of vignettes in an online survey, we find a relationship between racial attitudes and genetic attributions when respondents are asked to make causal attributions of differences between racial groups.

Small molecule peptidomimetic inhibitors of importin α/β mediated nuclear transport.

Nucleocytoplasmic transport of macromolecules is a fundamental process of eukaryotic cells. Translocation of proteins and many RNAs between the nucleus and cytoplasm is carried out by shuttling receptors of the β-karyopherin family, also called importins and exportins. Leptomycin B, a small molecule inhibitor of the exportin CRM1, has proved to be an invaluable tool for cell biologists, but up to now no small molecule inhibitors of nuclear import have been described.

The 'W.I.S.E. Up!' tool: empowering adopted children to cope with questions and comments about adoption.

Families of adopted children and the children themselves are not strangers to intrusive questions about private information, such as "Is that your real child (or mother)?" and "Why did your mother give you away?" While the questions may be benign, they can be uncomfortable to handle and harmful to a child's self-esteem. To counteract this, The Center for Adoption Support and Education (C.A.

Communicating disclosure risk in informed consent statements.

For several years, we have experimented with various ways of communicating disclosure risk and harm to respondents in order to determine how these affect their willingness to participate in surveys. These experiments, which used vignettes administered to an online panel as well as a mail survey sent to a national probability sample, have demonstrated that (a) the probability of disclosure alone has no apparent effect on people's willingness to participate in the survey described, (b) the sensitivity of the survey topic has such an effect, and (c) making explicit the possible harms that might result from disclosure also reduces willingness to participate, in both the vignette and the mail experiments. As a last study in this series, we experimented with different ways of describing disclosure risk in informed consent statements that might more plausibly be used in real surveys, again using vignettes administered to an online panel.

Are bi-axial proximal sesamoid bone fractures in the British Thoroughbred racehorse a bone fatigue related fracture? A histological study.

Objectives: To investigate whether microfractures and alterations in the trabecular bone area are associated with catastrophic bi-axial proximal sesamoid bone fractures (PSBF).

Methods: Proximal sesamoid bones (PSB) from 10 racehorses with PSBF and from 10 control racehorses without musculoskeletal injury were examined using the bulk basic fuchsin method. Bone histomorphometric and microfracture analysis was performed, and cases and controls compared using two-sample t-test, paired t-test, and Mann-Whitney U test.

CCL3 genotype and current depression increase risk of HIV-associated dementia.

BACKGROUND: The prevalence of Human immunodeficiency virus (HIV)-associated dementia (HAD) has continued to rise even as incidence has fallen. Several host genetic variants have been identified that modify risk for HAD. However, the findings have not been replicated consistently and most studies did not consider the multitude of factors that might themselves confer risk for HAD.

Medication and finance management among HIV-infected adults: the impact of age and cognition.

This study examined the effects of aging and cognitive impairment on medication and finance management in an HIV sample. We observed main effects of age (older < younger) and neuropsychological impairment on functional task performance. Interactions between age and cognition demonstrated that older impaired individuals performed significantly more poorly than all other comparison groups.

Targeted therapies for non-clear renal cell carcinoma.

The treatment of advanced and metastatic kidney cancer has been revolutionized by the development of targeted systemic therapies. Despite the growing number of available agents approved for use against clear cell renal cell carcinoma, patients with non-clear histologies, constituting approximately 1 in 4 cases of kidney cancer, have not received the same attention. The majority of clinical trials testing novel targeted therapies have excluded non-clear subtypes, providing limited therapeutic options for patients with these diagnoses and their oncologists.

Identification of a small molecule inhibitor of importin β mediated nuclear import by confocal on-bead screening of tagged one-bead one-compound libraries.

In eukaryotic cells, proteins and RNAs are transported between the nucleus and the cytoplasm by nuclear import and export receptors. Over the past decade, small molecules that inhibit the nuclear export receptor CRM1 have been identified, most notably leptomycin B. However, up to now no small molecule inhibitors of nuclear import have been described.

Catastrophic biaxial proximal sesamoid bone fractures in UK Thoroughbred races (1999-2004): horse characteristics and racing history.

Reason For Performing Study: Catastrophic biaxial proximal sesamoid bone fractures (PSBF) have not yet been described in detail in the UK racing population.

Objectives: To determine the incidence and relative risk (RR) of PSBF in different types of racing in the UK; and to describe horse-level characteristics and racing histories of horses sustaining these injuries.

Methods: Distal limbs were collected from all racehorses suffering catastrophic fractures during racing at all 59 racecourses in the UK, in a prospective study from February 1999 to December 2004.

Management of locally recurrent kidney cancer.

Locally recurrent kidney cancer is an uncommon but complicated problem. Due to the recognition of the importance of renal preservation and an increase in the use of nephron-sparing approaches via surgery or ablation, locally recurrent disease is being encountered with greater frequency. Treatments for locally recurrent kidney cancer include radical nephrectomy, repeat or salvage partial nephrectomy, de novo or repeat ablation, observation, or experimental systemic therapy.

Memantine for AIDS dementia complex: open-label report of ACTG 301.

Objective: To evaluate the long-term safety and efficacy of memantine use as treatment of HIV-associated cognitive impairment.

Background: The results of a 20-week, randomized, double-blind, placebo-controlled trial of memantine in HIV-infected participants with cognitive impairment (ACTG 301) were previously reported. We report the results of the up-to-60-week open-label phase following the double-blind phase.

The DECISIONS study: a nationwide survey of United States adults regarding 9 common medical decisions.

Background: Patient involvement is required before patients' preferences can be reflected in the medical care they receive. Furthermore, patients are a vital link between physicians' assessments of patients' needs and actual implementation of appropriate care. Yet no study has specifically examined how and when a representative sample of patients considered, discussed, and made medical decisions.

Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response.

In eukaryotes, fumarase (FH in human) is a well-known tricarboxylic-acid-cycle enzyme in the mitochondrial matrix. However, conserved from yeast to humans is a cytosolic isoenzyme of fumarase whose function in this compartment remains obscure. A few years ago, FH was surprisingly shown to underlie a tumor susceptibility syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC).