Dr. E. Richard Stiehm, a professor of pediatrics at the Mattel Children's Hospital at UCLA, researched examples throughout medical history of ways that one disease prevents another.

His findings suggest that genetic, infectious and metabolic influences should be considered when looking for treatments, particularly in regard to HIV/AIDS.

"Clinical observations of disease-versus-disease interactions have led to an understanding of the mechanisms of several diseases," Stiehm said. "In turn, these observations have led to the development of vaccines, therapeutic antibodies, medications and special diets."

Detailed in the January 2006 issue of Pediatrics, the official peer-reviewed journal of the American Academy of Pediatrics, Stiehm's research illustrated 12 disease pairs, reviewed their therapeutic implications and suggested additional applications.

A few of the pairings that Stiehm described include: Sickle cell disease and malaria. In 1948, British biologist J.B. Haldane proposed that malaria was an evolutionary force for selecting malaria-resistant genes. He suggested that those carrying the gene for sickle cell anemia were better able to survive in malaria-infected areas. Leprosy patients have severe immune defects and cutaneous anergy -- an inability to respond to skin testing. They hardly ever get psoriasis, a skin disorder. Starvation was used since biblical times for the treatment of seizures, which were believed to be demons. A 1924 discovery showed that a diet rich in fat and low in carbohydrates mimicked starvation by causing ketonemia and also controlled seizures. The ketogenic diet is still used today for cases of epilepsy resistant to medication. During the 1994 winter of starvation when bread supplies to the children's hospital were interrupted at The Hague, young patients with celiac disease, a digestive disease that damages the small intestine and interferes with absorption of nutrients from food, thrived on their "non-bread" diet. Wheat was discovered to be the culprit. Other diseases that benefit from severe caloric or protein restriction include kidney failure, type-II diabetes, inflammatory bowel disease and morbid obesity.

Overall, Stiehm proposed that new evidence can be found for using certain viruses to treat diseases such as HIV, which do not respond to other medications.

"There have been several studies indicating that HIV patients co-infected with a virus related to Hepatitis C, called GB virus C, have less severe HIV disease and improved survival," Stiehm said.

Stiehm got the idea for his historical review from cases he saw while a pediatric resident at Babies Hospital in New York City. One case was a kidney disease patient with nephrosis who was unresponsive to medications but went into remission after contracting measles. The other, a cystic fibrosis (CF) patient who needed to be admitted to the hospital, but there were no rooms available. Stiehm's supervisor, a CF specialist, told him, "put him in the room with the tuberculosis patient -- CF patients never get tuberculosis." Subsequent studies have confirmed this observation.

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To further test the connection, Svenningsson and his colleagues genetically engineered two strains of mice: one that produced more p11 than normal and another that produced no p11 at all. They found that mice that overexpress p11 were hyperactive and, in a test designed to identify depression in rodents, acted just like mice that were on anti-depressant medication. Mice that lacked p11, meanwhile, acted depressed and showed less responsivity to anti-depressant medications.

Taken together, the findings point to p11 as a new target for developing depression treatments.

"In addition to exploring ways to increase p11 in depressed patients, it may also be possible to develop peptide-based compounds that can mimic the action of p11 to achieve a new class of anti-depressant compounds," Svenningsson says.

In addition to Svenningsson and Greengard, the study's other authors are Ilan Rachleff and Marc Flajolet at Rockefeller; Karima Chergui and Xiaoqun Zhang at Karolinska; Malika El Yacoubi and Jean-Marie Vaugeois at the University of Rouen; and George G. Nomikos at Eli Lilly.

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