Right Ventricular Failure and Pulmonary Hypertension.

Right ventricular dysfunction is an important component of the pathophysiology of several disorders commonly encountered in the emergency department (ED). Interventions often performed routinely early in the ED course such as fluid administration and endotracheal intubation have the potential to cause precipitous clinical deterioration in patients with right ventricular failure and pulmonary hypertension. It is important for emergency physicians to understand the pathophysiology of acute decompensated right ventricular failure in order to avoid common pitfalls in diagnosis and management that can result in significant morbidity and mortality.

Should academic therapeutic patents go to the highest bidder?

Universities conduct biomedical research with the self-stated goal of disseminating the benefits to the global public. Licensing therapeutic patents to the highest bidder is counterproductive to this aim, as it prioritizes income maximization over dissemination. We believe that licensing strategies focused on promoting broad access to university-discovered therapeutics better serve both the mission of universities and the public good.

University contributions to the HPV vaccine and implications for access to vaccines in developing countries: addressing materials and know-how in university technology transfer policy.

Human Papillomavirus (HPV) is a major cause of morbidity and mortality worldwide, with most of the disease burden concentrated in developing countries. Over 90 percent of cervical cancer deaths, almost all of which are caused by HPV, occur in low- and middle-income countries where access to goods and services for prevention and treatment pose major barriers to intervention. In resource-poor settings lacking the capacity for routine screening for cervical cancer, the HPV vaccines developed by Merck and GlaxoSmithKline are desperately needed to help prevent these unnecessary deaths. The initial development of currently available HPV vaccines took place at a number of universities and other publicly funded institutions, yet there is little low-cost access to the vaccine in developing countries where access would be most critical. This is the rule rather than the exception with most university-discovered medicines. Universities and other publicly-funded institutions can adopt a number of licensing methods to ensure that vaccines discovered on their campuses are available at low-cost in developing countries. Universities Allied for Essential Medicines has proposed that universities adopt Global Access Licensing policies to implement these changes by enabling generic or low-cost production of the end product in developing countries. Generic competition is a critical market force that has, for instance, driven down the price of HIV/AIDS treatments from more than $10,000 to less than $99 per patient per year today. While the central barrier to creation of small molecule generics is patent-protection, there are multiple additional barriers that need to be addressed in order to ensure the efficient production of cost-effective generic vaccines and other biologics. While certain biologics may require generic producers to perform additional clinical trials, vaccines are in a somewhat unique situation with respect to both safety and efficacy. With access to appropriate patents, materials and knowledge, vaccines have the potential to be evaluated efficiently and cost-effectively via a pathway parallel to establishing bioequivalence for generic small molecule drugs. A new paradigm is needed that addresses the additional barriers that exist, outside of simply patent protection, to the generic production of vaccines and other biologics. One possible framework, which builds upon previous work on prize funds and patent pools, is discussed here: a Patents, Materials, and Know-how Pool (PMK Pool), based on the patent pool model such as those outlined in the Essential Medical Inventions Licensing Agency and proposals recently put forth by the governments of Barbados and Bolivia. University approaches to licensing vaccines and other biologics need to ensure access not only to patents, knowledge, and materials covered by intellectual property, but must also address the problem of access to materials and know-how that are often proprietary trade secrets. Universities should actively participate in the creation of this and other novel mechanisms, and in the meantime use currently available technology transfer mechanisms to ensure low-cost access to medicines in developing countries.

Prizes and parasites: incentive models for addressing Chagas disease.

Recent advances in immunology have provided a foundation of knowledge to understand many of the intricacies involved in manipulating the human response to fight parasitic infections, and a great deal has been learned from malaria vaccine efforts regarding strategies for developing parasite vaccines. There has been some encouraging progress in the development of a Chagas vaccine in animal models. A prize fund for Chagas could be instrumental in ensuring that these efforts are translated into products that benefit patients.

Social modulation of pain as evidence for empathy in mice.

Empathy is thought to be unique to higher primates, possibly to humans alone. We report the modulation of pain sensitivity in mice produced solely by exposure to their cagemates, but not to strangers, in pain. Mice tested in dyads and given an identical noxious stimulus displayed increased pain behaviors with statistically greater co-occurrence, effects dependent on visual observation. When familiar mice were given noxious stimuli of different intensities, their pain behavior was influenced by their neighbor's status bidirectionally. Finally, observation of a cagemate in pain altered pain sensitivity of an entirely different modality, suggesting that nociceptive mechanisms in general are sensitized.

Paclitaxel-induced neuropathic hypersensitivity in mice: responses in 10 inbred mouse strains.

Mechanical allodynia, or hypersensitivity to tactile stimuli, is a frequent clinical symptom of neuropathy. Large interindividual differences have been observed in neuropathic pain, both in susceptibility to its development and in its severity. Identification of genetic factors relevant to this variability would be of obvious utility. Although many animal models of neuropathic pain following peripheral nerve injury have been developed, most involve intricate surgeries and are thus poorly suited for large-scale linkage mapping investigations in the mouse. Recently, a schedule of intraperitoneal injections of the chemotherapeutic agent, paclitaxel (Taxol(R)), has been shown to produce a long-lasting, bilateral neuropathy in the rat, featuring hypersensitivity to mechanical, thermal and cold stimuli. We present here a survey of the responses of 10 inbred mouse strains to paclitaxel injections. Virtually all strains developed statistically significant mechanical allodynia, with one strain, DBA/2J, exhibiting especially robust changes. Strain sensitivities to paclitaxel-induced mechanical allodynia were similar to those obtained previously using a surgical model of neuropathic pain, supporting our contention that genetic sensitivity to mechanical allodynia is independent of the precise mode of induction. Using sensitive DBA/2 mice and a resistant strain, C57BL/6J, for comparison, we further characterized the paclitaxel model in mice by examining cold allodynia and thermal hyperalgesia. Both strains displayed equivalent cold allodynia but neither strain developed thermal hyperalgesia. The present data confirm a genetic component in mechanical allodynia using this model, while dissociating mechanical hypersensitivity from other pain modalities.