Win32 Virus Removal

Veterinary Topics: Marks of the 21st century

Posted: Saturday, March 12, 2005

Gene therapy, lasers among innovations in technology with promise for veterinary medicine

TWO AREAS of veterinary medicine that have seen significant advancements over the past several years are the fields of genetics and surgery. Collaborative efforts throughout the equine research community have produced an equine genome map that will aid in understanding, preventing, and treating disease.

Meanwhile, surgeons continue to discover new surgical techniques while using lasers instead of traditional scalpels. In many cases, it is no longer necessary for a horse to undergo traumatic, highly invasive surgery when a laser slipped through an endoscope can do the job without creating an external wound, which minimizes lay-up time for recovery.

Gene therapy for arthritis, tumors

Scientists are using the body's own defenses to combat cartilage breakdown and skin tumors prevalent in gray horses. Alan Nixon, B.V.Sc., M.S., professor of large animal surgery and director of the Comparative Orthopaedics Laboratory at Cornell University, is working on a project that piggybacks cartilage-stimulating growth factors on a virus that is injected into the horse's joint.

At University of California at Davis, Alain Theon, D.V.M., M.S., professor and chief of radiation oncology, also is working on a method to use the piggyback technique to deliver a vaccine into skin tumors.

Nixon has combined a virus that causes mild respiratory effects in humans with insulin-like growth factor (IGF-1) that stimulates cartilage cell metabolism and thereby maintains healthy joints.

"We're looking to get a better quality of cartilage matrix, in particular for the running horses that have so much trouble with their knees, especially in the carpal joints with cartilage degeneration," Nixon said.

"Viruses are very adept at getting into cells; that's how they create disease. The virus we use is an adenovirus, which creates a very mild form of respiratory disease in people. But it also is highly efficient at getting into all the cells.

"What we do is we take away the part of the virus that is involved in its self-replication, so it's a completely defunct virus once it gets into the system, but it gets in very nicely. So it carries in the growth factor gene, sets it up in the cells, and the cell then synthesizes its own growth factors. So it is like a self-supporting cell that synthesizes [what is needed] to stimulate [cartilage growth]."

Like a cultured pearl, the "cultured" cartilage matrix Nixon has been able to stimulate in the research trials is not quite as durable as naturally formed matrix.

"What we know so far is that we're getting toward the three-quarter matrix consistency, that's three-quarters of what it should be, but we've never gotten satisfactory levels of one of the cartilage components called a proteoglycan," he said. "It's very important because it gives the cartilage its resistance to compression."

Nixon estimates the proteoglycans they have stimulated are about half the durability of naturally occurring ones.

The current therapy using an adenovirus offers improvement for a limited time. Nixon is currently testing the use of an adeno-associated virus, closely related to the family of parvoviruses.

"The adenovirus is essentially a workhorse and it has worked very well for us," he said. "The down-side with it is that it does secrete small areas of viral protein, so the life expectancy of the synthesis fades. You may get a couple of months of stimulated cell function and stimulated growth factor synthesis, but we want a year or two. That's why the interest is moving away from adenovirus to adeno-associated virus.

"We still aren't getting normal cartilage, but we certainly saw an improvement over what we've been doing with just cartilage cells alone, so we have these gradual, baby steps, moving toward an ultimate success."

Although this technique, which requires just one injection, is limited to use in research trials, Nixon estimates it will be available for clinical application within the next three years.

Theon is attacking the problem of multiple melanomas through development of an autovaccine, one derived from the tumor cells of the horse under treatment, which is combined with a virus and then injected into the horse. Currently, there is no good, systemic way to treat a horse with multiple melanomas, he said.

"Tumor cells are [combined] with the virus in a way that the immune system thinks that it is fighting a viral infection," Theon said, "and the immune system, not knowing that it has been faked, essentially builds an immune response against the tumor cells while it is building an immune response against the virus.

"We want to be able to manage horses that have this disease, and, hopefully, if we can, at some point [we will] start to treat horses very early when they have minimal disease. This is not the type of vaccine where you give it before you get infected. It will always be used in horses that have the disease."

Theon said multiple melanomas are most prevalent in gray horses, which may be genetically predisposed to the disease. "With gray horses it isn't a matter of whether or not they will have it, but when it is going to be a big problem," he said. A separate research project at UC-Davis is attempting to ascertain if a mutation on the chromosome that causes gray coloring is the cause of melanomas.

21st-century scalpels

Lasers provide surgeons with a means of cutting into tissue that is minimally invasive, less traumatic, and causes less blood loss than traditional scalpel surgery. Lasers can be used to remove diseased tissue, such as large, abscessed areas or infected umbilicals. They also have oncological applications in battling squamous cell carcinomas, papillomas, sarcoids, and removing cancers from delicate areas of the eye. Lasers even can be used with such accuracy that they can grab a single blood cell and rotate it while leaving its neighboring cells unmoved.

Through the use of fiber optics, lasers can be guided through the horse's body to perform delicate surgeries in areas that were formerly difficult to reach.

According to H. David Moll, D.V.M., M.S., professor of equine surgery at Oklahoma State University and a board-certified surgeon, lasers are handy for performing respiratory tract surgery, removing uterine cysts, excising tumors, and even smashing stones in the urinary tract (uroliths) so they can be flushed out of the body as grains of sand. Their application in airway disease is used most frequently to correct entrapment of the epiglottis, remove cysts from the epiglottis and larynx, and relieve air pockets that swell the guttural pouches (tympany).

"A lot of people think if you do surgery with a laser, it's got to be better," Moll said. "That's not necessarily true. But for doing upper respiratory surgery, the biggest advantage is that you don't have to perform anesthesia. By not having to perform anesthesia and not having to make an external wound, the recovery time is two weeks instead of two or three months."

Moll said he recently used a laser to remove a cyst from the epiglottis of a young horse that he would have been unable to reach through the horse's mouth using conventional surgery. "With the laser, you can be much more precise," Moll said. "And the laser does tend to seal very small vessels and minimize bleeding, in particular in meticulous surgeries. It also is thought, but it's difficult to prove, that humans who have had laser surgery think it's less painful because it will seal the nerve endings, too."

Lasers also can be used to remove uterine cysts, and they may do a better job of keeping them from recurring. "By obliterating the lining or the place where the cysts come from, they don't tend to recur nearly so often as when we try to do them conventionally," Moll said.

Perhaps the most interesting application for lasers is their use in removing stones from the urinary tract. Using a pulsed dye laser, surgeons are able to zap uroliths with the beam to pulverize them into granules, which then can be flushed from the urinary tract.

"If you have a stone that's four inches in diameter, you're still in there 45 minutes or an hour," Moll said. "It's not like it pulverizes it immediately, but it sure saves doing a ventral midline incision, cutting into the bladder, spending $3,000, and having a horse laid up for three months. It can be done either anesthetized through the penis or going in through a urethroscope and flushing it out."

Removal of tumors can be challenging because of their tendency to recur if all the tumor cells are not excised. Lasers are superior to scalpels for this type of surgery, Moll said. "A scalpel blade or surgical instruments used for removing and handling malignant tumors also can pick up cells and spread [the malignancy] if you're not cautious," he added. "The laser doesn't have that problem because it sanitizes and cleans itself off as it cuts, so you are less likely to reinfect the wound with tumor cells."

A new, interesting application is called photodynamic therapy, which uses lasers to activate a drug injected into the horse's body that attaches to and accumulates in a targeted tumor. When the drug is activated, it creates oxygen and free radicals that shrink the tumor over a series of treatments.

On February 17, Intel Corp. announced its creation of a new silicon-transmitted laser that promises to be 10,000 times stronger than the current lasers, which are conveyed through glass fibers. When a laser beam is pumped through a special silicon chip, the natural atomic vibration in silicon amplifies the light as it passes through the chip.

According to Intel, the new technology has the potential to bring low-cost, high-quality lasers and optical devices to mainstream use in medical appliances, computing, and communications.

Denise Steffanus is a contributing editor of Thoroughbred Times who writes frequently on veterinary and farm management topics.

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