EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, July 19, 2004
To contact corresponding author Robert C. Holloway, M.D., M.P.H., call Leslie Briner at 585/275-1018.

LEVODOPA AND PRAMIPEXOLE BOTH APPEAR TO BE REASONABLE OPTIONS FOR INITIAL TREATMENT OF PARKINSON DISEASE

CHICAGO—The drugs levodopa and pramipexole both appear to be reasonable options as initial therapy for Parkinson disease, but they are associated with different efficacy and adverse effects, according to an article in the July issue of the Archives of Neurology, one of the JAMA/Archives journals.

Parkinson disease is a progressive neurologic disease. It is believed to be related to low levels of the important neurotransmitter (messenger) dopamine in certain parts of the brain. When the drug levodopa is taken orally, it crosses through the "blood-brain barrier" and is converted to dopamine. Another drug, carbidopa, is added to levodopa to prevent the breakdown of levodopa before it crosses into the brain. Pramipexole is one of several drugs that mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine.

The Parkinson Study Group conducted a multicenter, parallel-group, double-blind, randomized controlled trial to compare initial treatment with pramipexole vs. levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of motor complications, other adverse events, and functional and quality of life outcomes. Robert G. Holloway, M.D., M.P.H., of the University of Rochester, Rochester, N.Y., and colleagues reported the results for the Parkinson Study Group.

Patients with early Parkinson disease who required dopaminergic therapy (relating to nerve cells or fibers that employ dopamine as their neurotransmitter) to treat emerging disability enrolled in the study between October 1996 and August 1997. Among 301 patients, 151 were randomly assigned to receive 0.5 milligrams of pramipexole three times per day with levodopa placebo. The other 150 patients received 25/100 milligrams of carbidopa/levodopa three times per day with pramipexole placebo. Dosage was escalated during the first ten weeks for patients with ongoing disability. After that, the investigators were permitted to add open-label levodopa or other anti-Parkinsonian medications to treat ongoing or emerging disability. The patients were observed until August 2001.

"Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias [uncontrollable body movements; 24.5 percent vs. 54 percent with initial treatment with levodopa] and wearing off [47 percent vs. 62.7 percent with initial treatment with levodopa]," the authors write.

Initial levodopa treatment resulted in a significant reduction in the risk of "freezing" of motor function [25.3 percent vs. 37.1 percent with initial treatment with pramipexole], the researchers report.

Initial treatment with levodopa also resulted in lower incidences of somnolence (sleepiness; 36 percent vs. 21 percent), and edema (excess fluid in the tissues; 42 percent vs. 15 percent) and provided for better symptomatic control, as measured by the Unified Parkinson Disease Rating Scale.

By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the two groups. Both options resulted in similar quality of life.

"Pramipexole and levodopa are associated with different efficacy and adverse-effect profiles. These differences are insufficient to identify a preferred strategy; hence, both pramipexole and levodopa appear to be reasonable options as initial dopaminergic therapy in Parkinson disease," the authors conclude.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, July 19, 2004
To contact corresponding author Scott E. Kasner, M.D., call Karen Kreeger at 215/662-2560.

STROKE SEVERITY IS PREDOMINANT PREDICTOR OF DISCHARGE DESTINATION FOR PATIENTS

CHICAGO—Increasing stroke severity, as measured by the National Institutes of Health Stroke Scale, increases the likelihood that stroke patients who are treated with a clot-dissolving drug will be discharged to rehabilitation or nursing homes, rather than to their own homes, according to an article in the July issue of the Archives of Neurology, one of the JAMA/Archives journals.

A stroke is the sudden death of some brain cells due to a lack of oxygen when the blood flow to the brain is impaired by blockage or rupture of an artery to the brain. According to information in the article, early determination of discharge destination after acute stroke may promote earlier rehabilitation and reduce costs by shortening the duration of hospitalization. The National Institutes of Health Stroke Scale (NIHSS) is a widely used quantitative measure of stroke-related neurological deficit that includes items to assess level of consciousness, gaze, visual fields, facial palsy, motor strength, ataxia (wobbliness), sensation, language, dysarthria (slurred speech), and extinction or inattention.

Daniel J. Schlegel, M.D., of the University of Pennsylvania Medical Center, Philadelphia, and colleagues conducted a study to determine whether the NIHSS score predicts disposition in stroke patients treated with thrombolysis (administration of medication to dissolve a clot). The study included 546 patients from three countries with acute ischemic stroke, who were treated with recombinant tissue plasminogen activator (rt-PA), a powerful "clot-buster" that is infused through the vein. Medical records were reviewed for demographic information, vascular risk factors, location of stroke, initial NIHSS score, acute hospital disposition, and complications of symptomatic or asymptomatic intracerebral hemorrhage (ICH; bleeding within the brain tissue).

Of the 546 patients included in the study, 44 percent were discharged to home, 42 percent to rehabilitation, and 14 percent to a nursing facility.

"This study demonstrates that stroke severity, as measured by the NIHSS, is the predominant predictor of discharge destination after initial hospitalization for patients with acute ischemic stroke treated with intravenous rt-PA," the authors report.

Analysis showed that increasing NIHSS score was a robust and independent predictor of discharge to rehabilitation or nursing facilities, roughly doubling for each five-point increment.

The authors also found that symptomatic ICH was a devastating complication. "Patients who developed symptomatic ICH were never discharged to home," they write. But asymptomatic ICH had no significant independent effect on disposition.

"This multinational community and academic center-based study reinforces the usefulness of the NIHSS score as a predictor of disposition after stroke," the authors write. "The NIHSS score can predict discharge disposition when thrombolysis is used, although possibly with less precision than in patients not given this treatment."

The authors suggest that future studies should search for other variables rapidly available at admission like the NIHSS score, that could improve prediction of disposition after acute care.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, July 19, 2004
To contact Robert T. Dorr, Ph.D., call George Humphrey at 520/626-7301.

PRELIMINARY REPORT SUGGESTS THAT DRUG CAN INDUCE TANNING WHEN USED WITH SUNLIGHT OR SIMULATED UV-B LIGHT

CHICAGO—Melanotan-1, a synthetic agent similar to the body's hormone that regulates skin pigmentation, can be combined with UV-B light or sunlight, and appears to act synergistically in the tanning response to light, according to an article in the July issue of the Archives of Dermatology, one of the JAMA/Archives journals.

Melanotan-1 (MT-1) is a synthetic super-potent derivative of its natural counterpart, alpha-melanocyte-stimulating hormone, one of a family of hormones that induce pigmentation in the body. According to information in the article, the authors previously demonstrated that MT-1 can induce tanning in human volunteers who are known to tan easily in response to sunlight. All previously reported clinical trials with MT-1 were performed with volunteers who were instructed to avoid sunlight and use sunscreens with a sun-protective factor rating of 30 on all skin sites exposed to the sun. The effect of MT-1 when combined with either sunlight or simulated UV-B radiation had not been tested.

Robert T. Dorr, Ph.D., of the University of Arizona, Tucson, and colleagues performed three phase one clinical trials to demonstrate safety for MT-1 therapy combined with UV-B light or sunlight. In the first study, four subjects were randomized to 0.08 milligrams per kilogram of MT-1 per day administered by injection, and four others received injections of isotonic sodium chloride solution (solution containing the same concentration of salt as normal body fluids) for ten days. It was followed by neck irradiation with UV-B light.

In the second study, 12 subjects received MT-1. The dosage was increased to 0.16 milligrams per kilogram per day for ten days, with UV-B radiation given to a buttock site for five days during or after MT-1 administration. The final study randomized eight subjects to three to five days of sunlight to half of the back, or to sunlight plus 0.16 milligrams per kilogram of MT-1, for five days per week for four weeks.

"The results show that the synthetic super-potent melanotropin, MT-1, can be safely combined with small amounts of UV-B from a solar simulator or with brief exposures to full sunlight," the authors report. "We have further shown that MT-1 can be administered for 20 days over four weeks at a daily dose of 0.16 milligrams per kilogram without producing cumulative, more intense or new adverse effects."

Tanning was achieved in three of four subjects receiving MT-1 in the first study. These subjects also had 47 percent fewer sunburn cells at the irradiated site. More skin sites darkened with the higher dose of MT-1 in the second study. In the third study, there was significantly enhanced tanning in the MT-1 group, and it was maintained at least three weeks longer than the tanning in those who were randomized to sunlight only. The controls required 50 percent more sun exposure time for equivalent tanning.

"There were no pathologic findings at any UV-B or sun-exposed sites in any subject," the authors write. "Toxic effects due to MT-1 were minor, consisting of nausea and transient facial flushing."

EMBARGOED UNTIL 3 P.M. (CT), July 19, 2004
To contact Thomas L. Tzikas, M.D., call Heidi Suppo at 561/330-9500.

INJECTABLE SOFT TISSUE IMPLANT MATERIAL APPEARS EFFECTIVE IN FACIAL PLASTIC SURGERY

CHICAGO—The use of an injectable implant material appears effective and well tolerated by patients undergoing facial soft tissue augmentation, and patient satisfaction with treatment is high, according to an article in the July/August issue of the Archives of Facial Plastic Surgery, one of the JAMA/Archives journals.

According to information in the article, plastic and reconstructive surgery is among several clinical indications for soft tissue augmentation. According to the article, all the components of this material have been extensively used in implants and drug delivery systems, and its biocompatibility has been tested extensively in preclinical studies.

Thomas L. Tzikas, M.D., who is in private practice in Delray Beach, Fla., evaluated the clinical efficacy and patient satisfaction of a new product developed for soft tissue augmentation (Radiance FN). Dr. Tzikas studied 90 patients, aged 25 to 85, who underwent soft tissue injections with the product. The primary areas treated were lips, nasolabial (nose and upper lip) folds, glabellar rhytids (skin wrinkles in the area between the eyebrows), marionette lines (lines at the corner of the mouth), prejowl depressions, acne scars, and surgical soft tissue defects. Patients were surveyed after treatment and for up to six months for pain, ecchymosis (skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels), skin erythema (redness resulting from inflammation), nodules (small lumps, swelling, or collection of tissue), softness, appearance, and satisfaction.

"In terms of efficacy, at six months, appearance, softness, and overall patient satisfaction were rated good or excellent in 74 percent, 80 percent, and 88 percent of patients, respectively," Dr. Tzikas writes.

"Moderate or severe pain occurred with injection in 59 percent of patients, but disappeared two to five minutes after injection," he continues. "Erythema, edema [excess fluid in the tissues], and ecchymosis were common immediately after treatment but resolved in all patients within two weeks. Seven patients had persistent visible mucosal lip nodules, four of whom required intervention."

This product has been used for facial plastic surgery in more than 5,000 patients in the United States, Argentina, and Italy, but the follow-up to date has only been approximately three years. Dr. Tzikas suggests several questions remain regarding its use.

"Are there long-term adverse reactions associated with treatment?" he asks. "Does the implant stay soft in the face in the long term? How predictable is its use in mobile regions of the face?"