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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Potential causes of esophageal adenocarcinoma were identified by Mayne and her colleagues in a previously completed population-based, multi-center study of 1,095 cancer patients and 687 control subjects. As part of that study, they conducted a full dietary interview and had access to available data on consumption of both regular and diet soft drinks.

"Our team analyzed that data as the first direct test of the hypothesis that soft drinks might have contributed to the increase in this cancer," said Mayne. "We found that contrary to the hypothesis put forth by other researchers, carbonated soft drink consumption was inversely associated with esophageal adenocarcinoma risk, mainly attributable to diet soda, and that high intake did not increase risk of any esophageal or gastric cancer subtype in men or women."

Other Yale authors on the study included Harvey Risch, principal investigator of the grant that supported the work, Robert Dubrow, and Mayne's former student, Lauren Borchardt. Authors from other centers included Wong-Ho Chow, Marilie D. Gammon, Thomas L. Vaughan, Janet B. Schoenberg, Janet L. Stanford, A. Brian West, Heidi Rotterdam, William J. Blot and Joseph F. Fraumeni, Jr.

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