Recent Publications by CFE Educators

Translational regulation is critical in cancer development and progression. Translation sustains tumor growth and development of a tumor vasculature, a process known as angiogenesis, which is activated by hypoxia. Here we first demonstrate that a majority of large advanced breast cancers overexpress translation regulatory protein 4E-BP1 and initiation factor eIF4G. Using model animal and cell studies, we then show that overexpressed 4E-BP1 and eIF4G orchestrate a hypoxia-activated switch from cap-dependent to cap-independent mRNA translation that promotes increased tumor angiogenesis and growth at the level of selective mRNA translation. Elevated levels of 4E-BP1 trigger hypoxia inhibition of cap-dependent mRNA translation at high-oxygen levels and, with eIF4G, increase selective translation of mRNAs containing internal ribosome entry sites (IRESs) that include key proangiogenic, hypoxia, and survival mRNAs. The switch from cap-dependent to cap-independent mRNA translation facilitates tumor angiogenesis and hypoxia responses in animal models.

The Chornobyl (Chernobyl) accident in 1986 exposed many individuals to radioactive iodines, chiefly (131)I, the effects of which on benign thyroid diseases are largely unknown. To investigate the risk of follicular adenoma in relation to radiation dose after Chornobyl, the authors analyzed the baseline data from a prospective screening cohort study of those exposed as children or adolescents. A stratified random sample was selected from all individuals who were younger than 18 years, had thyroid radioactivity measurements taken within 2 months after the accident, and resided in the three heavily contaminated areas in Ukraine. This analysis is based on the 23 cases diagnosed in 12,504 subjects for whom personal history of thyroid diseases was known. The dose-response relation was linear with an excess relative risk of 2.07 per gray (95% confidence interval: 0.28, 10.31). The risk was significantly higher in women compared with men, with no clear modifying effects of age at exposure. In conclusion, persons exposed to radioactive iodines as children and adolescents have an increased risk of follicular adenoma, though it is smaller than the risk of thyroid cancer in the same cohort. Compared with results from other studies, this estimate is somewhat smaller, but confidence intervals overlap, suggesting compatibility.

Cardiovascular disease (CVD) is the primary cause of death among women worldwide. In the United States, more women than men die of CVD every year. Research has shown that there are important sex differences in terms of prevention, diagnosis, treatment, and outcomes in patients with CVD. Although women are being included in clinical trials in increasing numbers, lack of knowledge about sex differences persists because sex-specific analysis and reporting of sex-specific results remains limited. This knowledge gap limits the ability of health care professionals to provide optimal care for both women and men. Ongoing support and encouragement is needed for both the inclusion of sufficient numbers of women in clinical trials and for the reporting of sex-specific results of CVD trials. This increased knowledge and awareness can then be used to optimize high quality care for men and women.

This document presents the official recommendations of the American Gastroenterological Association (AGA) Institute Technology Assessment on "Image-Enhanced Endoscopy." It was approved by the Clinical Practice and Economics Committee on August 3, 2007, and by the AGA Institute Governing Board September 27, 2007.

BACKGROUND

There has been an increase in the incidence of endocrine diseases and the number of endocrine procedures in the United States. Higher surgeon volume is associated with improved patient outcomes. Fellowship programs will lead to more specialty-trained endocrine surgeons. We make projections for the supply of endocrine surgeons and demand for endocrine procedures over the next 15 years.

METHODS

Supply projections are based on data from the Accreditation Council for Graduate Medical Education, a survey of American Association of Endocrine Surgery fellowship program graduates, and Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS). Demand is estimated using HCUP-NIS, U.S. Census Bureau projections, and a literature review.

RESULTS

There were 64,275 endocrine procedures performed in 2000 and 80,505 in 2004. Using age-adjusted population projections and increasing incidence of endocrine diseases, 103,704 endocrine procedures are anticipated in 2020. High-volume endocrine surgeons are few in number, but perform 24% of endocrine procedures. Surgeon supply is projected to increase to 938 by 2020; this is based on fellowship graduation rates, retirement trends, and increasing annual endocrine case volume among high-volume surgeons. Alternative projections of supply and demand are generated to test the sensitivity of our analyses to different assumptions.

CONCLUSION

Labor force planning in endocrine surgery is essential if the demand for more high-volume endocrine specialists is to be met.

INTRODUCTION

Contemporary U.S. urologist's "real world" practice patterns in treating premature ejaculation (PE) are unknown.

AIM

To ascertain contemporary urologist practice patterns in the management of PE.

METHOD

A randomly generated mailing list of 1,009 practicing urologists was generated from the American Urologic Association (AUA) member directory. A custom-designed survey was mailed to these urologists with a cover letter and a return-address envelope. Responses were compared with the AUA 2004 guidelines for the treatment of PE.

MAIN OUTCOME MEASURES

The survey assessed several practice-related factors and asked questions of how the subject would handle various presentations of PE in their practice.

RESULTS

Responses from practicing urologists totaled 207 (21%). Eighty-four percent of the respondents were in private practice and 11% were in academics. Most urologists (73%) saw less than one PE patient per week. On-demand selective serotonin reuptake inhibitor (SSRI) therapy was the most commonly selected first line treatment (26%), with daily dosing a close second (22%). Combination SSRI therapy, the "stop/start" technique, the "squeeze" technique, and topical anesthetics were favored by 13, 18, 18, and 11% of the respondents, respectively. If primary treatment failed, changing dosing of SSRIs, topical anesthetics, and referral to psychiatry were increasingly popular options. Ten percent of urologists would treat PE before erectile dysfunction (ED) in a patient with both conditions, with the remainder of the respondents treating ED first, typically with a phosphodiesterase type 5 inhibitor (78% of total). Fifty-one percent of urologists report that they would inquire about the sexual partner, but only 8, 7, and 4% would evaluate, refer, or treat the partner, respectively.

CONCLUSIONS

The majority of our respondents diagnose PE by patient complaint, and treat ED before PE, as per the 2004 PE guidelines. Very few urologists offer referral or treatment to sexual partners of men suffering from PE. Additional randomized studies in the treatment of PE are needed.

The transient receptor potential cation channel, vanilloid family, type 2 (TRPV2) is a member of the TRPV family of proteins and is a homologue of the capsaicin/vanilloid receptor (transient receptor potential cation channel, vanilloid family, type 1, TRPV1). Like TRPV1, TRPV2 is expressed in a subset of dorsal root ganglia (DRG) neurons that project to superficial laminae of the spinal cord dorsal horn. Because noxious heat (>52 degrees C) activates TRPV2 in transfected cells this channel has been implicated in the processing of high intensity thermal pain messages in vivo. In contrast to TRPV1, however, which is restricted to small diameter DRG neurons, there is significant TRPV2 immunoreactivity in a variety of CNS regions. The present report focuses on a subset of neurons in the brainstem and spinal cord of the rat including the dorsal lateral nucleus (DLN) of the spinal cord, the nucleus ambiguus, and the motor trigeminal nucleus. Double label immunocytochemistry with markers of motoneurons, combined with retrograde labeling, established that these cells are, in fact, motoneurons. With the exception of their smaller diameter, these cells did not differ from other motoneurons, which are only lightly TRPV2-immunoreactive. As for the majority of DLN neurons, the densely-labeled populations co-express androgen receptor and follow normal DLN ontogeny. The functional significance of the very intense TRPV2 expression in these three distinct spinal cord and brainstem motoneurons groups remains to be determined.