Kerri Wachter

CHICAGO — Radiation segmentectomy offers an alternative treatment for unresectable liver carcinoma that avoids the complications of traditional external beam therapy, according to a study presented at the annual meeting of the Radiological Society of North America.

Radiation segmentectomy involves infusing an internal point source of radiation—in this case, yttrium-90 glass microspheres (MDS Nordion's TheraSpheres)—to the tumor site, said Robert J. Lewandowski, M.D., of William Beaumont Hospital, Royal Oak, Mich.

With radiation segmentectomy, “tumoricidal radiation doses approaching 5,000 Gy can be achieved in portions of the liver—i.e., in the tumor—with virtually no adverse clinical events,” he said.

In contrast, tumoricidal radiation doses delivered by traditional external beam therapy—via a collimated beam of radiation from an external source—typically range between 100 and 120 Gy. Radiation doses greater than 35 Gy given to normal parenchyma increase the risk of radiation hepatitis, which is characterized by alkaline phosphatase elevation, hepatomegaly, jaundice, and ascites. Patients typically require complex pretreatment planning.

In this study, 18 patients underwent Y90 microsphere treatment for unresectable hepatoma (12 patients) or metastatic liver disease (6 patients). The microspheres were infused via the hepatic artery to the right lobe in 13 patients, the left lobe in 4 patients, and both lobes in 1 patient. All patients had good performance status and normal liver function at baseline. All patients received treatment on an outpatient basis.

The median absorbed tumor dose was 926 Gy, and the median dose to normal parenchyma was 14 Gy. Results from liver function tests remained within normal limits for all patients for a median follow-up of 60 days. No patient showed signs of radiation hepatitis during the follow-up period.

The success rate for the procedure is greater than 30%, principal investigator Riad Salem, M.D., told this newspaper. The procedure can also be repeated if necessary. Dr. Salem is the director of radiation oncology at Northwestern Memorial Hospital, Chicago. He is also a consultant for MDS Nordion.

CHICAGO — Radiation segmentectomy offers an alternative treatment for unresectable liver carcinoma that avoids the complications of traditional external beam therapy, according to a study presented at the annual meeting of the Radiological Society of North America.

Radiation segmentectomy involves infusing an internal point source of radiation—in this case, yttrium-90 glass microspheres (MDS Nordion's TheraSpheres)—to the tumor site, said Robert J. Lewandowski, M.D., of William Beaumont Hospital, Royal Oak, Mich.

With radiation segmentectomy, “tumoricidal radiation doses approaching 5,000 Gy can be achieved in portions of the liver—i.e., in the tumor—with virtually no adverse clinical events,” he said.

In contrast, tumoricidal radiation doses delivered by traditional external beam therapy—via a collimated beam of radiation from an external source—typically range between 100 and 120 Gy. Radiation doses greater than 35 Gy given to normal parenchyma increase the risk of radiation hepatitis, which is characterized by alkaline phosphatase elevation, hepatomegaly, jaundice, and ascites. Patients typically require complex pretreatment planning.

In this study, 18 patients underwent Y90 microsphere treatment for unresectable hepatoma (12 patients) or metastatic liver disease (6 patients). The microspheres were infused via the hepatic artery to the right lobe in 13 patients, the left lobe in 4 patients, and both lobes in 1 patient. All patients had good performance status and normal liver function at baseline. All patients received treatment on an outpatient basis.

The median absorbed tumor dose was 926 Gy, and the median dose to normal parenchyma was 14 Gy. Results from liver function tests remained within normal limits for all patients for a median follow-up of 60 days. No patient showed signs of radiation hepatitis during the follow-up period.

The success rate for the procedure is greater than 30%, principal investigator Riad Salem, M.D., told this newspaper. The procedure can also be repeated if necessary. Dr. Salem is the director of radiation oncology at Northwestern Memorial Hospital, Chicago. He is also a consultant for MDS Nordion.

CHICAGO — Radiation segmentectomy offers an alternative treatment for unresectable liver carcinoma that avoids the complications of traditional external beam therapy, according to a study presented at the annual meeting of the Radiological Society of North America.

Radiation segmentectomy involves infusing an internal point source of radiation—in this case, yttrium-90 glass microspheres (MDS Nordion's TheraSpheres)—to the tumor site, said Robert J. Lewandowski, M.D., of William Beaumont Hospital, Royal Oak, Mich.

With radiation segmentectomy, “tumoricidal radiation doses approaching 5,000 Gy can be achieved in portions of the liver—i.e., in the tumor—with virtually no adverse clinical events,” he said.

In contrast, tumoricidal radiation doses delivered by traditional external beam therapy—via a collimated beam of radiation from an external source—typically range between 100 and 120 Gy. Radiation doses greater than 35 Gy given to normal parenchyma increase the risk of radiation hepatitis, which is characterized by alkaline phosphatase elevation, hepatomegaly, jaundice, and ascites. Patients typically require complex pretreatment planning.

In this study, 18 patients underwent Y90 microsphere treatment for unresectable hepatoma (12 patients) or metastatic liver disease (6 patients). The microspheres were infused via the hepatic artery to the right lobe in 13 patients, the left lobe in 4 patients, and both lobes in 1 patient. All patients had good performance status and normal liver function at baseline. All patients received treatment on an outpatient basis.

The median absorbed tumor dose was 926 Gy, and the median dose to normal parenchyma was 14 Gy. Results from liver function tests remained within normal limits for all patients for a median follow-up of 60 days. No patient showed signs of radiation hepatitis during the follow-up period.

The success rate for the procedure is greater than 30%, principal investigator Riad Salem, M.D., told this newspaper. The procedure can also be repeated if necessary. Dr. Salem is the director of radiation oncology at Northwestern Memorial Hospital, Chicago. He is also a consultant for MDS Nordion.

BUDAPEST, HUNGARY — Autoimmune striatal dysfunction may be the underlying cause of dementialike presentations, in rare cases.

This was the case for a 48-year-old woman, who presented with a 1-year history of progressive difficulties with attention and memory, said Gabriel C. Léger, M.D., speaking at the 4th International Congress on Autoimmunity.

Her husband noted a profound change in her personality. She had become uninhibited and exhaustingly hypersexual and had progressive difficulties functioning at home and at work—finally losing her job.

Her medical history included an episode of self-limiting, ballisticlike movements of the right side of her body during her early 20s. Exhaustive testing turned up no cause. The condition resolved spontaneously after a few months. She had no history of rheumatic fever or childhood chorea. However, at the age of 17 years her mother had Sydenham's chorea, which lasted about 1 year.

Cognitive testing also revealed attention and memory (acquisition) deficits. Additionally, the patient displayed frontal network dysfunction, which psychologic testing confirmed.

Her physical exam was unremarkable, except for mild psychomotor activity of the right hand and right side of the face, said Dr. Léger, a neurologist at the University of Montreal.

The clinicians initially diagnosed frontotemporal dementia, but “the presence of a very mild focal examination bothered us just a little bit,” said Dr. Léger. An FDG-PET scan revealed a dramatic increase in metabolism in the left striatum—70% more metabolic activity than in the right striatum.

Hypermetabolic lesions have traditionally been associated with diseases of autoimmunity, he noted. They treated her with a 3-day course of pulsed methylprednisolone sodium succinate, followed by a 2-week prednisone taper period.

Within weeks, the woman noted a resolution of her attention deficits. Neurocognitive assessments also indicated improvement. FDG-PET imaging demonstrated a fairly substantial resolution of the asymmetry of the striatum.

Based on the suspicion that autoimmunity against the basal ganglia was involved, the researchers sent pre- and post-therapy plasma to the laboratory for analysis. High titers of antibodies to the striatum—the antibodies found in Sydenham's chorea—were found in the pretreatment sample and reduced titers were found in the posttreatment sample.

Unlike this case, previously published studies involving hypermetabolic lesions have also involved previously diagnosed disorders, such as Sydenham's chorea, Dr. Léger said.

BUDAPEST, HUNGARY — Autoimmune striatal dysfunction may be the underlying cause of dementialike presentations, in rare cases.

This was the case for a 48-year-old woman, who presented with a 1-year history of progressive difficulties with attention and memory, said Gabriel C. Léger, M.D., speaking at the 4th International Congress on Autoimmunity.

Her husband noted a profound change in her personality. She had become uninhibited and exhaustingly hypersexual and had progressive difficulties functioning at home and at work—finally losing her job.

Her medical history included an episode of self-limiting, ballisticlike movements of the right side of her body during her early 20s. Exhaustive testing turned up no cause. The condition resolved spontaneously after a few months. She had no history of rheumatic fever or childhood chorea. However, at the age of 17 years her mother had Sydenham's chorea, which lasted about 1 year.

Cognitive testing also revealed attention and memory (acquisition) deficits. Additionally, the patient displayed frontal network dysfunction, which psychologic testing confirmed.

Her physical exam was unremarkable, except for mild psychomotor activity of the right hand and right side of the face, said Dr. Léger, a neurologist at the University of Montreal.

The clinicians initially diagnosed frontotemporal dementia, but “the presence of a very mild focal examination bothered us just a little bit,” said Dr. Léger. An FDG-PET scan revealed a dramatic increase in metabolism in the left striatum—70% more metabolic activity than in the right striatum.

Hypermetabolic lesions have traditionally been associated with diseases of autoimmunity, he noted. They treated her with a 3-day course of pulsed methylprednisolone sodium succinate, followed by a 2-week prednisone taper period.

Within weeks, the woman noted a resolution of her attention deficits. Neurocognitive assessments also indicated improvement. FDG-PET imaging demonstrated a fairly substantial resolution of the asymmetry of the striatum.

Based on the suspicion that autoimmunity against the basal ganglia was involved, the researchers sent pre- and post-therapy plasma to the laboratory for analysis. High titers of antibodies to the striatum—the antibodies found in Sydenham's chorea—were found in the pretreatment sample and reduced titers were found in the posttreatment sample.

Unlike this case, previously published studies involving hypermetabolic lesions have also involved previously diagnosed disorders, such as Sydenham's chorea, Dr. Léger said.

BUDAPEST, HUNGARY — Autoimmune striatal dysfunction may be the underlying cause of dementialike presentations, in rare cases.

This was the case for a 48-year-old woman, who presented with a 1-year history of progressive difficulties with attention and memory, said Gabriel C. Léger, M.D., speaking at the 4th International Congress on Autoimmunity.

Her husband noted a profound change in her personality. She had become uninhibited and exhaustingly hypersexual and had progressive difficulties functioning at home and at work—finally losing her job.

Her medical history included an episode of self-limiting, ballisticlike movements of the right side of her body during her early 20s. Exhaustive testing turned up no cause. The condition resolved spontaneously after a few months. She had no history of rheumatic fever or childhood chorea. However, at the age of 17 years her mother had Sydenham's chorea, which lasted about 1 year.

Cognitive testing also revealed attention and memory (acquisition) deficits. Additionally, the patient displayed frontal network dysfunction, which psychologic testing confirmed.

Her physical exam was unremarkable, except for mild psychomotor activity of the right hand and right side of the face, said Dr. Léger, a neurologist at the University of Montreal.

The clinicians initially diagnosed frontotemporal dementia, but “the presence of a very mild focal examination bothered us just a little bit,” said Dr. Léger. An FDG-PET scan revealed a dramatic increase in metabolism in the left striatum—70% more metabolic activity than in the right striatum.

Hypermetabolic lesions have traditionally been associated with diseases of autoimmunity, he noted. They treated her with a 3-day course of pulsed methylprednisolone sodium succinate, followed by a 2-week prednisone taper period.

Within weeks, the woman noted a resolution of her attention deficits. Neurocognitive assessments also indicated improvement. FDG-PET imaging demonstrated a fairly substantial resolution of the asymmetry of the striatum.

Based on the suspicion that autoimmunity against the basal ganglia was involved, the researchers sent pre- and post-therapy plasma to the laboratory for analysis. High titers of antibodies to the striatum—the antibodies found in Sydenham's chorea—were found in the pretreatment sample and reduced titers were found in the posttreatment sample.

Unlike this case, previously published studies involving hypermetabolic lesions have also involved previously diagnosed disorders, such as Sydenham's chorea, Dr. Léger said.

In patients with rheumatoid arthritis, methotrexate significantly reduces abnormally elevated levels of plasmatic sRANKL, the main cytokine involved in inducing osteoporosis and bone erosions, Doina Baltaru, M.D., reported at the 4th International Congress on Autoimmunity.

Soluble RANKL (receptor activator of nuclear factor-kappa B ligand) is a member of the tumor necrosis factor cytokines and plays a major role in the regulation of bone remodeling, specifically in the stimulation of osteoclast formation, said Dr. Baltaru, of the Emergency Military Hospital in Cluj-Napoca, Romania.

Dr. Baltaru and her colleagues evaluated plasma sRANKL levels of 15 patients with rheumatoid arthritis, who had never received corticosteroids or disease-modifying antirheumatic drugs.

The study participants were assessed before and after 3 months of methotrexate therapy (15 mg/week). sRANKL levels were also evaluated in 7 healthy controls and 10 patients with type I osteoporosis.

Plasma sRANKL values were determined by quantitative enzyme-linked immunosorbent assay. At baseline, the median sRANKL value for RA patients was 467 pg/mL, though there was a wide variation (70-1,500 pg/mL). Levels ranged between 10-30 pg/mL for normal subjects and 20-200 pg/mL in patients with osteoporosis.

Methotrexate therapy significantly reduced plasma sRANKL levels in the rheumatoid arthritis patients, to a median value of 185 pg/mL.

In patients with rheumatoid arthritis, methotrexate significantly reduces abnormally elevated levels of plasmatic sRANKL, the main cytokine involved in inducing osteoporosis and bone erosions, Doina Baltaru, M.D., reported at the 4th International Congress on Autoimmunity.

Soluble RANKL (receptor activator of nuclear factor-kappa B ligand) is a member of the tumor necrosis factor cytokines and plays a major role in the regulation of bone remodeling, specifically in the stimulation of osteoclast formation, said Dr. Baltaru, of the Emergency Military Hospital in Cluj-Napoca, Romania.

Dr. Baltaru and her colleagues evaluated plasma sRANKL levels of 15 patients with rheumatoid arthritis, who had never received corticosteroids or disease-modifying antirheumatic drugs.

The study participants were assessed before and after 3 months of methotrexate therapy (15 mg/week). sRANKL levels were also evaluated in 7 healthy controls and 10 patients with type I osteoporosis.

Plasma sRANKL values were determined by quantitative enzyme-linked immunosorbent assay. At baseline, the median sRANKL value for RA patients was 467 pg/mL, though there was a wide variation (70-1,500 pg/mL). Levels ranged between 10-30 pg/mL for normal subjects and 20-200 pg/mL in patients with osteoporosis.

Methotrexate therapy significantly reduced plasma sRANKL levels in the rheumatoid arthritis patients, to a median value of 185 pg/mL.

In patients with rheumatoid arthritis, methotrexate significantly reduces abnormally elevated levels of plasmatic sRANKL, the main cytokine involved in inducing osteoporosis and bone erosions, Doina Baltaru, M.D., reported at the 4th International Congress on Autoimmunity.

Soluble RANKL (receptor activator of nuclear factor-kappa B ligand) is a member of the tumor necrosis factor cytokines and plays a major role in the regulation of bone remodeling, specifically in the stimulation of osteoclast formation, said Dr. Baltaru, of the Emergency Military Hospital in Cluj-Napoca, Romania.

Dr. Baltaru and her colleagues evaluated plasma sRANKL levels of 15 patients with rheumatoid arthritis, who had never received corticosteroids or disease-modifying antirheumatic drugs.

The study participants were assessed before and after 3 months of methotrexate therapy (15 mg/week). sRANKL levels were also evaluated in 7 healthy controls and 10 patients with type I osteoporosis.

Plasma sRANKL values were determined by quantitative enzyme-linked immunosorbent assay. At baseline, the median sRANKL value for RA patients was 467 pg/mL, though there was a wide variation (70-1,500 pg/mL). Levels ranged between 10-30 pg/mL for normal subjects and 20-200 pg/mL in patients with osteoporosis.

Methotrexate therapy significantly reduced plasma sRANKL levels in the rheumatoid arthritis patients, to a median value of 185 pg/mL.

BUDAPEST, HUNGARY — Chloroquine therapy for patients with rheumatoid arthritis may lower levels of antibodies to oxidized low-density lipoprotein, and thus reduce the risk of cardiovascular disease, C.L.P. Mangueira, M.D., reported at the 4th International Congress on Autoimmunity.

Oxidized low-density lipoprotein (oxLDL) induces antibody production and the inflammatory process. These antibodies (anti-oxLDL) are also considered risk factors for cardiovascular disease.

In a study of 66 rheumatoid arthritis (RA) patients and 66 age-matched healthy controls, “we found an apparent association between the use of chloroquine and low levels of the antibodies to oxidized LDL,” said Dr. Mangueira of Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.

The researchers evaluated the levels of anti-oxLDL in RA patients by two different assays developed by Dr. Mangueira's group and compared them with those of the control group.

RA patients were using methotrexate, prednisone, sulfasalazine, chloroquine, and leflunomide.

“We found higher levels of anti-oxLDL in rheumatoid patients compared with the control group,” using both methods, Dr. Mangueira said. There was no statistical correlation between anti-oxLDL levels and disease severity, which was assessed using the Modified Disease Activity Score system, the erythrocyte sedimentation rate, and C-reactive protein.

The 22 RA patients on chloroquine therapy had lower levels of anti-ox-LDL than did RA patients with no chloroquine use. In addition, the RA patients taking chloroquine had lower levels of anti-apolipoprotein B peptides than did those not taking the drug.

BUDAPEST, HUNGARY — Chloroquine therapy for patients with rheumatoid arthritis may lower levels of antibodies to oxidized low-density lipoprotein, and thus reduce the risk of cardiovascular disease, C.L.P. Mangueira, M.D., reported at the 4th International Congress on Autoimmunity.

Oxidized low-density lipoprotein (oxLDL) induces antibody production and the inflammatory process. These antibodies (anti-oxLDL) are also considered risk factors for cardiovascular disease.

In a study of 66 rheumatoid arthritis (RA) patients and 66 age-matched healthy controls, “we found an apparent association between the use of chloroquine and low levels of the antibodies to oxidized LDL,” said Dr. Mangueira of Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.

The researchers evaluated the levels of anti-oxLDL in RA patients by two different assays developed by Dr. Mangueira's group and compared them with those of the control group.

RA patients were using methotrexate, prednisone, sulfasalazine, chloroquine, and leflunomide.

“We found higher levels of anti-oxLDL in rheumatoid patients compared with the control group,” using both methods, Dr. Mangueira said. There was no statistical correlation between anti-oxLDL levels and disease severity, which was assessed using the Modified Disease Activity Score system, the erythrocyte sedimentation rate, and C-reactive protein.

The 22 RA patients on chloroquine therapy had lower levels of anti-ox-LDL than did RA patients with no chloroquine use. In addition, the RA patients taking chloroquine had lower levels of anti-apolipoprotein B peptides than did those not taking the drug.

BUDAPEST, HUNGARY — Chloroquine therapy for patients with rheumatoid arthritis may lower levels of antibodies to oxidized low-density lipoprotein, and thus reduce the risk of cardiovascular disease, C.L.P. Mangueira, M.D., reported at the 4th International Congress on Autoimmunity.

Oxidized low-density lipoprotein (oxLDL) induces antibody production and the inflammatory process. These antibodies (anti-oxLDL) are also considered risk factors for cardiovascular disease.

In a study of 66 rheumatoid arthritis (RA) patients and 66 age-matched healthy controls, “we found an apparent association between the use of chloroquine and low levels of the antibodies to oxidized LDL,” said Dr. Mangueira of Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo, Brazil.

The researchers evaluated the levels of anti-oxLDL in RA patients by two different assays developed by Dr. Mangueira's group and compared them with those of the control group.

RA patients were using methotrexate, prednisone, sulfasalazine, chloroquine, and leflunomide.

“We found higher levels of anti-oxLDL in rheumatoid patients compared with the control group,” using both methods, Dr. Mangueira said. There was no statistical correlation between anti-oxLDL levels and disease severity, which was assessed using the Modified Disease Activity Score system, the erythrocyte sedimentation rate, and C-reactive protein.

The 22 RA patients on chloroquine therapy had lower levels of anti-ox-LDL than did RA patients with no chloroquine use. In addition, the RA patients taking chloroquine had lower levels of anti-apolipoprotein B peptides than did those not taking the drug.

PARIS — The risk of infection from bites varies considerably depending on the type of wound that is inflicted, and therefore careful assessment and treatment are required, according to wound experts speaking at a meeting of the World Union of Wound Healing Societies.

In the United States, bites account for 0.4% of all emergency department visits each year, said U. Lenz, M.D., a surgeon in Sindelfingen, Germany. On an annual basis, dog bites make up 80% (1 million to 2 million) of bite wounds; cat bites account for up to 15% (about 400,000); and human bites account for 2%-3%.

Dogs and cats typically bite adults on the head, shoulders, or arms; they tend to bite children on the head and neck. Human bites on the arms and hands are usually the result of aggression; those that are on the breasts, genitals, and thighs are usually the result of sexual acts, Dr. Lenz said.

Although dog bites may be the most common, only 2%-20% of them become infected. In contrast, as many as 50% of cat and human bites become infected. Risk factors for infection include location (hand or foot), deep puncture wounds, long delays in treatment, immunosuppression, and preexisting muscular disease.

Most infections develop as the result of puncture wounds. Of the infectious agents in dog and cat bites, Pasteurella bacteria are the most common, followed by Streptococcus and Staphylococcus species. Human bites have a high risk of infection because as many as 190 species of microorganisms can be found in the human mouth. In particular, human bite wounds average five to nine species of microorganisms, with Streptococcus and S. aureus being the most common.

The wounds of fewer than 20% of those bitten by a rabid animal become infected, Dr. Lenz said.

Wild animals—primarily raccoons, skunks, bats, and foxes—accounted for 93% of U.S. rabies cases in 2001, according to the Centers for Disease Control and Prevention.

The CDC recommends observing healthy animals for 10 days after a biting incident. Patients should not be given rabies prophylaxis unless the animal develops clinical signs of the disease.

If an animal is suspected of having rabies, vaccination should be started immediately. Rabies vaccines are administered intramuscularly in the upper arm following a bite from a rabid animal.

Tetanus shots also should be considered, said Dr. Laurence Le Mouel, a wound specialist at Hôpital Sainte Perrine in Paris. If the patient has never been vaccinated for tetanus, do so. If more than 5 years have elapsed since the last shot, administer a booster.

The diagnosis of a bite wound should be made based on the patient's immune status and history as well as the circumstances surrounding the bite.

During the exam, determine the type of bite damage—puncture vs. crush—and the depth of the wound; then assess nerve and tendon function. Powerful canine jaws typically result in crush wounds, while sharp feline teeth usually inflict puncture wounds.

Only infected wounds need to be cultured. X-rays can be useful in identifying fractures and foreign bodies.

Closed-fist injuries are the most common and significant type of human bites. These injuries typically occur during a fight when a fist strikes the teeth of another person with enough force to create a small wound.

In spite of their small size, these injuries have a very high risk of infection, said Dr. Le Mouel, because relaxation of the hand carries bacteria deeper into the tissues. Surgical exploration is crucial with this type of injury.

Dr. Lenz recommends an aggressive surgical approach—extensive exploration and thorough debridement—for every bite deeper than a superficial wound. Thoroughly irrigate the wound with a sterile solution. If viral transmission is suspected, use an antiseptic solution such as Betadine, Dr. Le Mouel advised. Bite wounds can generally be left open; however, bites of the face and hand should be closed, Dr. Lenz noted.

Prophylactic antibiotics are recommended for human bites, delayed presentations, immunocompromised patients, and deep puncture wounds. “We use mainly amoxicillin/clavulanate [Augmentin] or the second-generation cephalosporins,” Dr. Lenz said. He typically uses the amoxicillin/clavulanate combination in doses of 875 mg given twice a day or 500 mg given three times a day.

Negative-pressure therapy is a good option for treating bite wounds, because it improves drainage, reduces local edema, and decreases local bacterial colonization.

Dr. Lenz recommends that bites on the hands, eyes, or face—or anywhere in children—be referred to a plastic surgeon.

Preventing Dog Bites: Eight Tips

Dog bites account for at least 80% of all bite wounds in the United States each year, so patients should be informed of ways to avoid being bitten. The Centers for Disease Control and Prevention recommends using the following behavior around dogs:

▸ Do not approach an unfamiliar dog.

▸ Do not scream and run from a dog.

▸ Remain motionless when an unfamiliar dog approaches you.

▸ If you are knocked over by a dog, roll into a ball and lie still.

▸ Do not allow children to play with a dog unless supervised by an adult.

▸ Avoid direct eye contact with a dog.

▸ Do not disturb a dog that is sleeping, eating, or caring for puppies.

▸ Do not pet a dog without first letting it see and smell you.

PARIS — The risk of infection from bites varies considerably depending on the type of wound that is inflicted, and therefore careful assessment and treatment are required, according to wound experts speaking at a meeting of the World Union of Wound Healing Societies.

In the United States, bites account for 0.4% of all emergency department visits each year, said U. Lenz, M.D., a surgeon in Sindelfingen, Germany. On an annual basis, dog bites make up 80% (1 million to 2 million) of bite wounds; cat bites account for up to 15% (about 400,000); and human bites account for 2%-3%.

Dogs and cats typically bite adults on the head, shoulders, or arms; they tend to bite children on the head and neck. Human bites on the arms and hands are usually the result of aggression; those that are on the breasts, genitals, and thighs are usually the result of sexual acts, Dr. Lenz said.

Although dog bites may be the most common, only 2%-20% of them become infected. In contrast, as many as 50% of cat and human bites become infected. Risk factors for infection include location (hand or foot), deep puncture wounds, long delays in treatment, immunosuppression, and preexisting muscular disease.

Most infections develop as the result of puncture wounds. Of the infectious agents in dog and cat bites, Pasteurella bacteria are the most common, followed by Streptococcus and Staphylococcus species. Human bites have a high risk of infection because as many as 190 species of microorganisms can be found in the human mouth. In particular, human bite wounds average five to nine species of microorganisms, with Streptococcus and S. aureus being the most common.

The wounds of fewer than 20% of those bitten by a rabid animal become infected, Dr. Lenz said.

Wild animals—primarily raccoons, skunks, bats, and foxes—accounted for 93% of U.S. rabies cases in 2001, according to the Centers for Disease Control and Prevention.

The CDC recommends observing healthy animals for 10 days after a biting incident. Patients should not be given rabies prophylaxis unless the animal develops clinical signs of the disease.

If an animal is suspected of having rabies, vaccination should be started immediately. Rabies vaccines are administered intramuscularly in the upper arm following a bite from a rabid animal.

Tetanus shots also should be considered, said Dr. Laurence Le Mouel, a wound specialist at Hôpital Sainte Perrine in Paris. If the patient has never been vaccinated for tetanus, do so. If more than 5 years have elapsed since the last shot, administer a booster.

The diagnosis of a bite wound should be made based on the patient's immune status and history as well as the circumstances surrounding the bite.

During the exam, determine the type of bite damage—puncture vs. crush—and the depth of the wound; then assess nerve and tendon function. Powerful canine jaws typically result in crush wounds, while sharp feline teeth usually inflict puncture wounds.

Only infected wounds need to be cultured. X-rays can be useful in identifying fractures and foreign bodies.

Closed-fist injuries are the most common and significant type of human bites. These injuries typically occur during a fight when a fist strikes the teeth of another person with enough force to create a small wound.

In spite of their small size, these injuries have a very high risk of infection, said Dr. Le Mouel, because relaxation of the hand carries bacteria deeper into the tissues. Surgical exploration is crucial with this type of injury.

Dr. Lenz recommends an aggressive surgical approach—extensive exploration and thorough debridement—for every bite deeper than a superficial wound. Thoroughly irrigate the wound with a sterile solution. If viral transmission is suspected, use an antiseptic solution such as Betadine, Dr. Le Mouel advised. Bite wounds can generally be left open; however, bites of the face and hand should be closed, Dr. Lenz noted.

Prophylactic antibiotics are recommended for human bites, delayed presentations, immunocompromised patients, and deep puncture wounds. “We use mainly amoxicillin/clavulanate [Augmentin] or the second-generation cephalosporins,” Dr. Lenz said. He typically uses the amoxicillin/clavulanate combination in doses of 875 mg given twice a day or 500 mg given three times a day.

Negative-pressure therapy is a good option for treating bite wounds, because it improves drainage, reduces local edema, and decreases local bacterial colonization.

Dr. Lenz recommends that bites on the hands, eyes, or face—or anywhere in children—be referred to a plastic surgeon.

Preventing Dog Bites: Eight Tips

Dog bites account for at least 80% of all bite wounds in the United States each year, so patients should be informed of ways to avoid being bitten. The Centers for Disease Control and Prevention recommends using the following behavior around dogs:

▸ Do not approach an unfamiliar dog.

▸ Do not scream and run from a dog.

▸ Remain motionless when an unfamiliar dog approaches you.

▸ If you are knocked over by a dog, roll into a ball and lie still.

▸ Do not allow children to play with a dog unless supervised by an adult.

▸ Avoid direct eye contact with a dog.

▸ Do not disturb a dog that is sleeping, eating, or caring for puppies.

▸ Do not pet a dog without first letting it see and smell you.

PARIS — The risk of infection from bites varies considerably depending on the type of wound that is inflicted, and therefore careful assessment and treatment are required, according to wound experts speaking at a meeting of the World Union of Wound Healing Societies.

In the United States, bites account for 0.4% of all emergency department visits each year, said U. Lenz, M.D., a surgeon in Sindelfingen, Germany. On an annual basis, dog bites make up 80% (1 million to 2 million) of bite wounds; cat bites account for up to 15% (about 400,000); and human bites account for 2%-3%.

Dogs and cats typically bite adults on the head, shoulders, or arms; they tend to bite children on the head and neck. Human bites on the arms and hands are usually the result of aggression; those that are on the breasts, genitals, and thighs are usually the result of sexual acts, Dr. Lenz said.

Although dog bites may be the most common, only 2%-20% of them become infected. In contrast, as many as 50% of cat and human bites become infected. Risk factors for infection include location (hand or foot), deep puncture wounds, long delays in treatment, immunosuppression, and preexisting muscular disease.

Most infections develop as the result of puncture wounds. Of the infectious agents in dog and cat bites, Pasteurella bacteria are the most common, followed by Streptococcus and Staphylococcus species. Human bites have a high risk of infection because as many as 190 species of microorganisms can be found in the human mouth. In particular, human bite wounds average five to nine species of microorganisms, with Streptococcus and S. aureus being the most common.

The wounds of fewer than 20% of those bitten by a rabid animal become infected, Dr. Lenz said.

Wild animals—primarily raccoons, skunks, bats, and foxes—accounted for 93% of U.S. rabies cases in 2001, according to the Centers for Disease Control and Prevention.

The CDC recommends observing healthy animals for 10 days after a biting incident. Patients should not be given rabies prophylaxis unless the animal develops clinical signs of the disease.

If an animal is suspected of having rabies, vaccination should be started immediately. Rabies vaccines are administered intramuscularly in the upper arm following a bite from a rabid animal.

Tetanus shots also should be considered, said Dr. Laurence Le Mouel, a wound specialist at Hôpital Sainte Perrine in Paris. If the patient has never been vaccinated for tetanus, do so. If more than 5 years have elapsed since the last shot, administer a booster.

The diagnosis of a bite wound should be made based on the patient's immune status and history as well as the circumstances surrounding the bite.

During the exam, determine the type of bite damage—puncture vs. crush—and the depth of the wound; then assess nerve and tendon function. Powerful canine jaws typically result in crush wounds, while sharp feline teeth usually inflict puncture wounds.

Only infected wounds need to be cultured. X-rays can be useful in identifying fractures and foreign bodies.

Closed-fist injuries are the most common and significant type of human bites. These injuries typically occur during a fight when a fist strikes the teeth of another person with enough force to create a small wound.

In spite of their small size, these injuries have a very high risk of infection, said Dr. Le Mouel, because relaxation of the hand carries bacteria deeper into the tissues. Surgical exploration is crucial with this type of injury.

Dr. Lenz recommends an aggressive surgical approach—extensive exploration and thorough debridement—for every bite deeper than a superficial wound. Thoroughly irrigate the wound with a sterile solution. If viral transmission is suspected, use an antiseptic solution such as Betadine, Dr. Le Mouel advised. Bite wounds can generally be left open; however, bites of the face and hand should be closed, Dr. Lenz noted.

Prophylactic antibiotics are recommended for human bites, delayed presentations, immunocompromised patients, and deep puncture wounds. “We use mainly amoxicillin/clavulanate [Augmentin] or the second-generation cephalosporins,” Dr. Lenz said. He typically uses the amoxicillin/clavulanate combination in doses of 875 mg given twice a day or 500 mg given three times a day.

Negative-pressure therapy is a good option for treating bite wounds, because it improves drainage, reduces local edema, and decreases local bacterial colonization.

Dr. Lenz recommends that bites on the hands, eyes, or face—or anywhere in children—be referred to a plastic surgeon.

Preventing Dog Bites: Eight Tips

Dog bites account for at least 80% of all bite wounds in the United States each year, so patients should be informed of ways to avoid being bitten. The Centers for Disease Control and Prevention recommends using the following behavior around dogs:

▸ Do not approach an unfamiliar dog.

▸ Do not scream and run from a dog.

▸ Remain motionless when an unfamiliar dog approaches you.

▸ If you are knocked over by a dog, roll into a ball and lie still.

▸ Do not allow children to play with a dog unless supervised by an adult.

▸ Avoid direct eye contact with a dog.

▸ Do not disturb a dog that is sleeping, eating, or caring for puppies.

▸ Do not pet a dog without first letting it see and smell you.

King Pharmaceuticals Inc. and the Food and Drug Administration are warning physicians about the inappropriate use of Bicillin C-R (penicillin G benzathine and penicillin G procaine injectable suspension) for the treatment of syphilis.

Bicillin L-A (penicillin G benzathine injectable suspension) is the only currently approved penicillin G benzathine product indicated for use in sexually transmitted infections such as syphilis.

The company has received postmarketing reports from several STD clinics in the United States where Bicillin C-R was used instead of Bicillin L-A to treat patients with syphilis.

The company is changing the packaging and syringe labels of Bicillin C-R to highlight the distinction between that product and Bicillin L-A.

There also have been reports of inadvertent intravenous administration of both drugs, which has been associated with cardiorespiratory arrest and death. The correct way to administer both drugs is by deep intramuscular injection. The warning sections of both labels have been changed to more prominently emphasize proper administration.

For more information, contact King Pharmaceuticals by calling 800-546-4905.

King Pharmaceuticals Inc. and the Food and Drug Administration are warning physicians about the inappropriate use of Bicillin C-R (penicillin G benzathine and penicillin G procaine injectable suspension) for the treatment of syphilis.

Bicillin L-A (penicillin G benzathine injectable suspension) is the only currently approved penicillin G benzathine product indicated for use in sexually transmitted infections such as syphilis.

The company has received postmarketing reports from several STD clinics in the United States where Bicillin C-R was used instead of Bicillin L-A to treat patients with syphilis.

The company is changing the packaging and syringe labels of Bicillin C-R to highlight the distinction between that product and Bicillin L-A.

There also have been reports of inadvertent intravenous administration of both drugs, which has been associated with cardiorespiratory arrest and death. The correct way to administer both drugs is by deep intramuscular injection. The warning sections of both labels have been changed to more prominently emphasize proper administration.

For more information, contact King Pharmaceuticals by calling 800-546-4905.

King Pharmaceuticals Inc. and the Food and Drug Administration are warning physicians about the inappropriate use of Bicillin C-R (penicillin G benzathine and penicillin G procaine injectable suspension) for the treatment of syphilis.

Bicillin L-A (penicillin G benzathine injectable suspension) is the only currently approved penicillin G benzathine product indicated for use in sexually transmitted infections such as syphilis.

The company has received postmarketing reports from several STD clinics in the United States where Bicillin C-R was used instead of Bicillin L-A to treat patients with syphilis.

The company is changing the packaging and syringe labels of Bicillin C-R to highlight the distinction between that product and Bicillin L-A.

There also have been reports of inadvertent intravenous administration of both drugs, which has been associated with cardiorespiratory arrest and death. The correct way to administer both drugs is by deep intramuscular injection. The warning sections of both labels have been changed to more prominently emphasize proper administration.

For more information, contact King Pharmaceuticals by calling 800-546-4905.

PHILADELPHIA — The race to find clinical cardiology applications for combined PET/CT technology is officially on, now that the results from the first round of studies have been presented at the annual meeting of the Society of Nuclear Medicine.

Combined PET/CT scanners have stimulated interest in imaging circles by offering clinicians the ability to combine noninvasive assessments of anatomy and function in one imaging session.

Based on the studies presented at the meeting—which showed the technology to be more sensitive at detecting stenotic/ischemic coronary artery disease (CAD) than coronary angiography and proved it useful in usually hard-to-image obese patients—combined PET/CT seems to be living up to all of the excitement the prospect of its use had generated.

In a study of 25 patients with known CAD, researchers at University Hospital Zurich (Switzerland), evaluated the feasibility and image quality of integrated PET/CT to assess coronary anatomy and perfusion.

Patients underwent contrast-enhanced CT angiography with retrospective ECG gating and rest, and adenosine stress myocardial perfusion PET scans using N-13 ammonia. The patients were also assessed by coronary angiography. Six patients already had undergone coronary artery bypass graft procedures. Of note, 22 of the 25 were male.

For each patient, the researchers evaluated a total of 100 segments from four vessels—left main coronary artery, left anterior descending coronary artery, left circumflex artery, and right coronary artery. They also analyzed the 12 bypass grafts. The CT scans take only a few minutes, and the PET scans take about an hour.

With conventional angiography, the researchers found 65 normal vessel segments, compared with 51 normal vessels identified by CT. “A few of the lesions considered as not significant by angiography, revealed ischemia on the PET scan,” said P.T. Siegrist, M.D., of the hospital. Overall PET/CT imaging had a sensitivity of 90% and a specificity of 98%.

The researchers also compared the decision whether to revascularize based on the PET/CT findings to the clinical decision for revascularization obtained by using PET alone to assess myocardial perfusion and coronary angiography to assess anatomy. Only the combination of a stenotic lesion and ischemia prompted a decision to revascularize.

With conventional angiography, 11 vessel segments qualified for revascularization. Likewise, PET/CT identified 11 vessel segments that qualified for revascularization. “We found excellent agreement [between] two techniques for determining whether revascularization was needed or not,” Dr. Siegrist said.

The study was funded in part by GE Medical Systems and Amersham Health.

In a similar study, researchers at Brigham and Women's Hospital in Boston combined rubidium-82 PET scans to assess myocardial perfusion and CT to assess anatomy in patients known or suspected of having CAD.

Marcelo F. Di Carli, M.D., and his colleagues from Brigham and Women's Hospital, Boston, performed gated rest/stress 82Rb PET/CT myocardial perfusion imaging on 94 consecutive patients (41 women) with known (21 patients) or suspected (73 patients) CAD. Stress imaging was performed with dipyridamole, adenosine, or dobutamine infusions. The studies were completed in about 45 minutes.

Most patients were overweight or obese, with an average body mass index of 30. In spite of this, the image quality was very good or excellent for all of the patients. In all, 38 patients were found to have abnormal myocardial perfusion, and 2 patients had probable myocardial perfusion abnormalities. Myocardial perfusion was normal in 53 patients and probably normal in 1 patient, Dr. Di Carli said.

PET/CT assessment of myocardial perfusion using

PHILADELPHIA — The race to find clinical cardiology applications for combined PET/CT technology is officially on, now that the results from the first round of studies have been presented at the annual meeting of the Society of Nuclear Medicine.

Combined PET/CT scanners have stimulated interest in imaging circles by offering clinicians the ability to combine noninvasive assessments of anatomy and function in one imaging session.

Based on the studies presented at the meeting—which showed the technology to be more sensitive at detecting stenotic/ischemic coronary artery disease (CAD) than coronary angiography and proved it useful in usually hard-to-image obese patients—combined PET/CT seems to be living up to all of the excitement the prospect of its use had generated.

In a study of 25 patients with known CAD, researchers at University Hospital Zurich (Switzerland), evaluated the feasibility and image quality of integrated PET/CT to assess coronary anatomy and perfusion.

Patients underwent contrast-enhanced CT angiography with retrospective ECG gating and rest, and adenosine stress myocardial perfusion PET scans using N-13 ammonia. The patients were also assessed by coronary angiography. Six patients already had undergone coronary artery bypass graft procedures. Of note, 22 of the 25 were male.

For each patient, the researchers evaluated a total of 100 segments from four vessels—left main coronary artery, left anterior descending coronary artery, left circumflex artery, and right coronary artery. They also analyzed the 12 bypass grafts. The CT scans take only a few minutes, and the PET scans take about an hour.

With conventional angiography, the researchers found 65 normal vessel segments, compared with 51 normal vessels identified by CT. “A few of the lesions considered as not significant by angiography, revealed ischemia on the PET scan,” said P.T. Siegrist, M.D., of the hospital. Overall PET/CT imaging had a sensitivity of 90% and a specificity of 98%.

The researchers also compared the decision whether to revascularize based on the PET/CT findings to the clinical decision for revascularization obtained by using PET alone to assess myocardial perfusion and coronary angiography to assess anatomy. Only the combination of a stenotic lesion and ischemia prompted a decision to revascularize.

With conventional angiography, 11 vessel segments qualified for revascularization. Likewise, PET/CT identified 11 vessel segments that qualified for revascularization. “We found excellent agreement [between] two techniques for determining whether revascularization was needed or not,” Dr. Siegrist said.

The study was funded in part by GE Medical Systems and Amersham Health.

In a similar study, researchers at Brigham and Women's Hospital in Boston combined rubidium-82 PET scans to assess myocardial perfusion and CT to assess anatomy in patients known or suspected of having CAD.

Marcelo F. Di Carli, M.D., and his colleagues from Brigham and Women's Hospital, Boston, performed gated rest/stress 82Rb PET/CT myocardial perfusion imaging on 94 consecutive patients (41 women) with known (21 patients) or suspected (73 patients) CAD. Stress imaging was performed with dipyridamole, adenosine, or dobutamine infusions. The studies were completed in about 45 minutes.

Most patients were overweight or obese, with an average body mass index of 30. In spite of this, the image quality was very good or excellent for all of the patients. In all, 38 patients were found to have abnormal myocardial perfusion, and 2 patients had probable myocardial perfusion abnormalities. Myocardial perfusion was normal in 53 patients and probably normal in 1 patient, Dr. Di Carli said.

PET/CT assessment of myocardial perfusion using

PHILADELPHIA — The race to find clinical cardiology applications for combined PET/CT technology is officially on, now that the results from the first round of studies have been presented at the annual meeting of the Society of Nuclear Medicine.

Combined PET/CT scanners have stimulated interest in imaging circles by offering clinicians the ability to combine noninvasive assessments of anatomy and function in one imaging session.

Based on the studies presented at the meeting—which showed the technology to be more sensitive at detecting stenotic/ischemic coronary artery disease (CAD) than coronary angiography and proved it useful in usually hard-to-image obese patients—combined PET/CT seems to be living up to all of the excitement the prospect of its use had generated.

In a study of 25 patients with known CAD, researchers at University Hospital Zurich (Switzerland), evaluated the feasibility and image quality of integrated PET/CT to assess coronary anatomy and perfusion.

Patients underwent contrast-enhanced CT angiography with retrospective ECG gating and rest, and adenosine stress myocardial perfusion PET scans using N-13 ammonia. The patients were also assessed by coronary angiography. Six patients already had undergone coronary artery bypass graft procedures. Of note, 22 of the 25 were male.

For each patient, the researchers evaluated a total of 100 segments from four vessels—left main coronary artery, left anterior descending coronary artery, left circumflex artery, and right coronary artery. They also analyzed the 12 bypass grafts. The CT scans take only a few minutes, and the PET scans take about an hour.

With conventional angiography, the researchers found 65 normal vessel segments, compared with 51 normal vessels identified by CT. “A few of the lesions considered as not significant by angiography, revealed ischemia on the PET scan,” said P.T. Siegrist, M.D., of the hospital. Overall PET/CT imaging had a sensitivity of 90% and a specificity of 98%.

The researchers also compared the decision whether to revascularize based on the PET/CT findings to the clinical decision for revascularization obtained by using PET alone to assess myocardial perfusion and coronary angiography to assess anatomy. Only the combination of a stenotic lesion and ischemia prompted a decision to revascularize.

With conventional angiography, 11 vessel segments qualified for revascularization. Likewise, PET/CT identified 11 vessel segments that qualified for revascularization. “We found excellent agreement [between] two techniques for determining whether revascularization was needed or not,” Dr. Siegrist said.

The study was funded in part by GE Medical Systems and Amersham Health.

In a similar study, researchers at Brigham and Women's Hospital in Boston combined rubidium-82 PET scans to assess myocardial perfusion and CT to assess anatomy in patients known or suspected of having CAD.

Marcelo F. Di Carli, M.D., and his colleagues from Brigham and Women's Hospital, Boston, performed gated rest/stress 82Rb PET/CT myocardial perfusion imaging on 94 consecutive patients (41 women) with known (21 patients) or suspected (73 patients) CAD. Stress imaging was performed with dipyridamole, adenosine, or dobutamine infusions. The studies were completed in about 45 minutes.

Most patients were overweight or obese, with an average body mass index of 30. In spite of this, the image quality was very good or excellent for all of the patients. In all, 38 patients were found to have abnormal myocardial perfusion, and 2 patients had probable myocardial perfusion abnormalities. Myocardial perfusion was normal in 53 patients and probably normal in 1 patient, Dr. Di Carli said.

PET/CT assessment of myocardial perfusion using

PHILADELPHIA – The activation of certain regions of a drug addict's brain following drug use may shed light on the compulsive nature of addiction, according to data presented at the annual meeting of the Society of Nuclear Medicine.

Using 18fluorodeoxyglucose PET imaging, researchers at Brookhaven National Laboratory in Upton, N.Y., found that cocaine addicts have an increase in brain activation in the orbitofrontal cortex after exposure to methylphenidate, which is similar in effect to cocaine. In contrast, healthy control subjects in the study had a decrease in activity in the same region, said Nora D. Volkow, M.D., lead researcher and director of the National Institute on Drug Abuse, Rockville, Md. “They're going in opposite directions. This becomes very significant.”

The difference in the response to methylphenidate suggests that abnormal recruitment of the orbitofrontal cortex–which is involved with salience, attribution, motivation, and drive–may reinforce the saliency of the drug. Moreover, this region is associated with compulsive behaviors, “so its abnormal activation could underlie the compulsive drug intake that occurs in addicted subjects,” Dr. Volkow said.

In the study, brain metabolism was measured in 21 cocaine-addicted men and 15 nonaddicted men as controls. All subjects underwent two PET scans. Both groups were imaged following two sequential placebos given 90 minutes apart and following two sequential doses of methylphenidate–0.5 mg/kg and 0.25 mg/kg–given intravenously 90 minutes apart.

The investigators used two sequential doses because cocaine abusers “do not take drugs in isolation–they do it compulsively,” Dr. Volkow said. Methylphenidate was chosen because, like cocaine, it blocks dopamine transporters. In addition, cocaine users report that methylphenidate's effects are similar to those of cocaine.

Cocaine abusers were an average of 36 years old and met the DSM-IV criteria for cocaine dependence. They used 3 g of cocaine per week, with continuous use for at least 6 months prior to the study, and averaged 13 years of use.

In self-reports of feelings of being high, control subjects had a greater response to the first dose than the second dose. Cocaine abusers also reported a greater high with the first dose, but the magnitude of their response was much lower than for the control subjects, she said.

In self-reports of craving, the control subjects reported very little craving for methylphenidate. In contrast, the first methylphenidate dose induced very strong cravings in the cocaine users and the second (and lower) dose induced cravings that were not as strong.

When the researchers specifically compared the differences in brain metabolic response between placebo and methylphenidate, cocaine abusers had a significant increase in metabolism in the right orbitofrontal cortex, while normal subjects had a decrease in metabolism. For the cocaine abusers, this increased activity in the right orbitofrontal cortex corresponded well with self-reports of cocaine craving.

These findings lend credence to the hypothesis that the orbitofrontal cortex and anterior cingulate gyrus play a major role in the manifestation of drug addiction. “Both of these regions are extremely important in assigning saliency to stimulations and also in exerting inhibitory control,” Dr. Volkow said.

In a related study, the researchers looked at the effect of expectation on brain activity in nonaddicted subjects.

Twelve healthy subjects with minimal prior drug experience (average age 33 years) were imaged using fluorodeoxyglucose PET under four conditions: the subject expected placebo and received placebo (baseline); the subject expected placebo but received methylphenidate; the subject expected methylphenidate and received methylphenidate; and the subject expected methylphenidate but received placebo. The order of the conditions was randomized for each patient. A dose of 0.5 mg methylphenidate was given intravenously 5 minutes prior to the PET scan.

Self-reports of high and drug effects from the subjects corresponded well with methylphenidate use, regardless of expectation. There was in increase in glucose metabolism, particularly in the cerebellum, when methylphenidate was given, regardless of whether or not it was expected. With the administration of unexpected methylphenidate, there were also increases in metabolism in the right frontal cortex. However, the expectation of methylphenidate alone activated the orbitofrontal cortex, which “is the same finding that we obtained in cocaine abusers,” Dr. Volkow said.

The finding that there is no difference between expected and unexpected methylphenidate in nonabusing subjects contrasts studies with cocaine abusers, in which expectation enhanced the effect of methylphenidate. This bolsters the relevance of learned experiences on brain responses to drugs of abuse. Activation of the orbitofrontal cortex by expectation alone suggests this region is involved in the processing of unexpected stimuli, she said.

PHILADELPHIA – The activation of certain regions of a drug addict's brain following drug use may shed light on the compulsive nature of addiction, according to data presented at the annual meeting of the Society of Nuclear Medicine.

Using 18fluorodeoxyglucose PET imaging, researchers at Brookhaven National Laboratory in Upton, N.Y., found that cocaine addicts have an increase in brain activation in the orbitofrontal cortex after exposure to methylphenidate, which is similar in effect to cocaine. In contrast, healthy control subjects in the study had a decrease in activity in the same region, said Nora D. Volkow, M.D., lead researcher and director of the National Institute on Drug Abuse, Rockville, Md. “They're going in opposite directions. This becomes very significant.”

The difference in the response to methylphenidate suggests that abnormal recruitment of the orbitofrontal cortex–which is involved with salience, attribution, motivation, and drive–may reinforce the saliency of the drug. Moreover, this region is associated with compulsive behaviors, “so its abnormal activation could underlie the compulsive drug intake that occurs in addicted subjects,” Dr. Volkow said.

In the study, brain metabolism was measured in 21 cocaine-addicted men and 15 nonaddicted men as controls. All subjects underwent two PET scans. Both groups were imaged following two sequential placebos given 90 minutes apart and following two sequential doses of methylphenidate–0.5 mg/kg and 0.25 mg/kg–given intravenously 90 minutes apart.

The investigators used two sequential doses because cocaine abusers “do not take drugs in isolation–they do it compulsively,” Dr. Volkow said. Methylphenidate was chosen because, like cocaine, it blocks dopamine transporters. In addition, cocaine users report that methylphenidate's effects are similar to those of cocaine.

Cocaine abusers were an average of 36 years old and met the DSM-IV criteria for cocaine dependence. They used 3 g of cocaine per week, with continuous use for at least 6 months prior to the study, and averaged 13 years of use.

In self-reports of feelings of being high, control subjects had a greater response to the first dose than the second dose. Cocaine abusers also reported a greater high with the first dose, but the magnitude of their response was much lower than for the control subjects, she said.

In self-reports of craving, the control subjects reported very little craving for methylphenidate. In contrast, the first methylphenidate dose induced very strong cravings in the cocaine users and the second (and lower) dose induced cravings that were not as strong.

When the researchers specifically compared the differences in brain metabolic response between placebo and methylphenidate, cocaine abusers had a significant increase in metabolism in the right orbitofrontal cortex, while normal subjects had a decrease in metabolism. For the cocaine abusers, this increased activity in the right orbitofrontal cortex corresponded well with self-reports of cocaine craving.

These findings lend credence to the hypothesis that the orbitofrontal cortex and anterior cingulate gyrus play a major role in the manifestation of drug addiction. “Both of these regions are extremely important in assigning saliency to stimulations and also in exerting inhibitory control,” Dr. Volkow said.

In a related study, the researchers looked at the effect of expectation on brain activity in nonaddicted subjects.

Twelve healthy subjects with minimal prior drug experience (average age 33 years) were imaged using fluorodeoxyglucose PET under four conditions: the subject expected placebo and received placebo (baseline); the subject expected placebo but received methylphenidate; the subject expected methylphenidate and received methylphenidate; and the subject expected methylphenidate but received placebo. The order of the conditions was randomized for each patient. A dose of 0.5 mg methylphenidate was given intravenously 5 minutes prior to the PET scan.

Self-reports of high and drug effects from the subjects corresponded well with methylphenidate use, regardless of expectation. There was in increase in glucose metabolism, particularly in the cerebellum, when methylphenidate was given, regardless of whether or not it was expected. With the administration of unexpected methylphenidate, there were also increases in metabolism in the right frontal cortex. However, the expectation of methylphenidate alone activated the orbitofrontal cortex, which “is the same finding that we obtained in cocaine abusers,” Dr. Volkow said.

The finding that there is no difference between expected and unexpected methylphenidate in nonabusing subjects contrasts studies with cocaine abusers, in which expectation enhanced the effect of methylphenidate. This bolsters the relevance of learned experiences on brain responses to drugs of abuse. Activation of the orbitofrontal cortex by expectation alone suggests this region is involved in the processing of unexpected stimuli, she said.

PHILADELPHIA – The activation of certain regions of a drug addict's brain following drug use may shed light on the compulsive nature of addiction, according to data presented at the annual meeting of the Society of Nuclear Medicine.

Using 18fluorodeoxyglucose PET imaging, researchers at Brookhaven National Laboratory in Upton, N.Y., found that cocaine addicts have an increase in brain activation in the orbitofrontal cortex after exposure to methylphenidate, which is similar in effect to cocaine. In contrast, healthy control subjects in the study had a decrease in activity in the same region, said Nora D. Volkow, M.D., lead researcher and director of the National Institute on Drug Abuse, Rockville, Md. “They're going in opposite directions. This becomes very significant.”

The difference in the response to methylphenidate suggests that abnormal recruitment of the orbitofrontal cortex–which is involved with salience, attribution, motivation, and drive–may reinforce the saliency of the drug. Moreover, this region is associated with compulsive behaviors, “so its abnormal activation could underlie the compulsive drug intake that occurs in addicted subjects,” Dr. Volkow said.

In the study, brain metabolism was measured in 21 cocaine-addicted men and 15 nonaddicted men as controls. All subjects underwent two PET scans. Both groups were imaged following two sequential placebos given 90 minutes apart and following two sequential doses of methylphenidate–0.5 mg/kg and 0.25 mg/kg–given intravenously 90 minutes apart.

The investigators used two sequential doses because cocaine abusers “do not take drugs in isolation–they do it compulsively,” Dr. Volkow said. Methylphenidate was chosen because, like cocaine, it blocks dopamine transporters. In addition, cocaine users report that methylphenidate's effects are similar to those of cocaine.

Cocaine abusers were an average of 36 years old and met the DSM-IV criteria for cocaine dependence. They used 3 g of cocaine per week, with continuous use for at least 6 months prior to the study, and averaged 13 years of use.

In self-reports of feelings of being high, control subjects had a greater response to the first dose than the second dose. Cocaine abusers also reported a greater high with the first dose, but the magnitude of their response was much lower than for the control subjects, she said.

In self-reports of craving, the control subjects reported very little craving for methylphenidate. In contrast, the first methylphenidate dose induced very strong cravings in the cocaine users and the second (and lower) dose induced cravings that were not as strong.

When the researchers specifically compared the differences in brain metabolic response between placebo and methylphenidate, cocaine abusers had a significant increase in metabolism in the right orbitofrontal cortex, while normal subjects had a decrease in metabolism. For the cocaine abusers, this increased activity in the right orbitofrontal cortex corresponded well with self-reports of cocaine craving.

These findings lend credence to the hypothesis that the orbitofrontal cortex and anterior cingulate gyrus play a major role in the manifestation of drug addiction. “Both of these regions are extremely important in assigning saliency to stimulations and also in exerting inhibitory control,” Dr. Volkow said.

In a related study, the researchers looked at the effect of expectation on brain activity in nonaddicted subjects.

Twelve healthy subjects with minimal prior drug experience (average age 33 years) were imaged using fluorodeoxyglucose PET under four conditions: the subject expected placebo and received placebo (baseline); the subject expected placebo but received methylphenidate; the subject expected methylphenidate and received methylphenidate; and the subject expected methylphenidate but received placebo. The order of the conditions was randomized for each patient. A dose of 0.5 mg methylphenidate was given intravenously 5 minutes prior to the PET scan.

Self-reports of high and drug effects from the subjects corresponded well with methylphenidate use, regardless of expectation. There was in increase in glucose metabolism, particularly in the cerebellum, when methylphenidate was given, regardless of whether or not it was expected. With the administration of unexpected methylphenidate, there were also increases in metabolism in the right frontal cortex. However, the expectation of methylphenidate alone activated the orbitofrontal cortex, which “is the same finding that we obtained in cocaine abusers,” Dr. Volkow said.

The finding that there is no difference between expected and unexpected methylphenidate in nonabusing subjects contrasts studies with cocaine abusers, in which expectation enhanced the effect of methylphenidate. This bolsters the relevance of learned experiences on brain responses to drugs of abuse. Activation of the orbitofrontal cortex by expectation alone suggests this region is involved in the processing of unexpected stimuli, she said.

WASHINGTON – It is important to balance risks with benefits when considering a selective serotonin reuptake inhibitor to treat a child or adolescent, several experts said at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The session came soon after the Food and Drug Administration's decision to require pharmaceutical companies to add a black box warning alerting prescribers to the risk of suicidal behavior with antidepressants in pediatric patients.

“I think this is very important. This is not a contraindication. This [warning] box is not telling clinicians that they can't use these drugs. What it's saying is that if a clinician is considering using an antidepressant in a child or adolescent, they need to consider the risk and balance that against the clinical need,” said Thomas Laughren, M.D., of the FDA's division of neuropharmacological drug products, Rockville, Md.

Selective serotonin reuptake inhibitors (SSRIs) do appear to work better than placebo in the short-term therapy of depression in children and adolescents, said Neal Ryan, M.D., of the Western Psychiatric Institute and Clinic in Pittsburgh. This is probably true in general, though fluoxetine is the only one with an indication for children.

Combining an SSRI with cognitive-behavioral therapy (CBT) might even be more effective, according to recent findings. In the Treatment for Adolescents With Depression Study (TADS), SSRIs combined with CBT showed the best results for treating depression. The results also suggested that pharmacotherapy is more effective than psychotherapy alone, but this finding needs to be duplicated in other studies, Dr. Ryan said.

For clinicians, the real problem is how to balance the increased short-term risk–an extra 2 per 100 patients who will either attempt suicide or exhibit suicidality because of the use of an SSRI–and the potentially decreased long-term risk of suicidal thoughts and behavior attributable to depression, Dr. Ryan said.

Clinicians are left with the dilemma of what to do about the next depressed child to come into the office: Pick an SSRI alone, choose psychotherapy alone, or combine an SSRI with psychotherapy. “I think we're going to have a rich debate on that,” Dr. Ryan said.

When considering an SSRI in a pediatric patient, it's important to inform the family of the potential risks and benefits and follow the FDA's monitoring suggestions. “I think also that we need to advocate for more studies. I think we're all scared that we won't get any more data on this question,” he said.

Mark Olfson, M.D., of Columbia University, New York, is not optimistic about the prospects for this type of research: “For the foreseeable future, I believe the pharmaceutical industry is going to view this whole area as radioactive and stay away from it.”

He does, however, think that this kind of research is necessary. “We need to think about this finding in the context of risks and benefits. So, paradoxically, now is the time that we need more information about what are the benefits of SSRIs in kids,” he said.

Future research should focus on which subgroups of patients are at higher risk and when in the course of treatment they are at higher risk. One strategy would be to monitor depressed children closely for short periods of SSRI therapy, looking for somatic subjective dysphoria, changes in attention, changes in impulsivity, or other indicators of suicidality, Dr. Olfson said.

It's also important to look at the bigger public health picture, Dr. Olfson said. “We need to be clear about the distinctions between suicidal ideation and the suicide attempts that were the subject of the randomized controlled trials analyses and actual suicide or serial suicide attempts that we encounter in practice.”

The rates of suicidal ideation and suicide attempts in a normal adolescent population also need to be considered. According to the Centers for Disease Control and Prevention's 2003 National Youth Risk Behavior Survey, 16.9% of normal adolescents in grades 9-12 had seriously considered attempting suicide in the previous 12 months and 8.5% had attempted suicide at least once in that time period.

Those numbers stand in sharp contrast to the comparatively small number of kids who show up in emergency rooms and hospitals after actual suicide attempts, Dr. Olfson said.

WASHINGTON – It is important to balance risks with benefits when considering a selective serotonin reuptake inhibitor to treat a child or adolescent, several experts said at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The session came soon after the Food and Drug Administration's decision to require pharmaceutical companies to add a black box warning alerting prescribers to the risk of suicidal behavior with antidepressants in pediatric patients.

“I think this is very important. This is not a contraindication. This [warning] box is not telling clinicians that they can't use these drugs. What it's saying is that if a clinician is considering using an antidepressant in a child or adolescent, they need to consider the risk and balance that against the clinical need,” said Thomas Laughren, M.D., of the FDA's division of neuropharmacological drug products, Rockville, Md.

Selective serotonin reuptake inhibitors (SSRIs) do appear to work better than placebo in the short-term therapy of depression in children and adolescents, said Neal Ryan, M.D., of the Western Psychiatric Institute and Clinic in Pittsburgh. This is probably true in general, though fluoxetine is the only one with an indication for children.

Combining an SSRI with cognitive-behavioral therapy (CBT) might even be more effective, according to recent findings. In the Treatment for Adolescents With Depression Study (TADS), SSRIs combined with CBT showed the best results for treating depression. The results also suggested that pharmacotherapy is more effective than psychotherapy alone, but this finding needs to be duplicated in other studies, Dr. Ryan said.

For clinicians, the real problem is how to balance the increased short-term risk–an extra 2 per 100 patients who will either attempt suicide or exhibit suicidality because of the use of an SSRI–and the potentially decreased long-term risk of suicidal thoughts and behavior attributable to depression, Dr. Ryan said.

Clinicians are left with the dilemma of what to do about the next depressed child to come into the office: Pick an SSRI alone, choose psychotherapy alone, or combine an SSRI with psychotherapy. “I think we're going to have a rich debate on that,” Dr. Ryan said.

When considering an SSRI in a pediatric patient, it's important to inform the family of the potential risks and benefits and follow the FDA's monitoring suggestions. “I think also that we need to advocate for more studies. I think we're all scared that we won't get any more data on this question,” he said.

Mark Olfson, M.D., of Columbia University, New York, is not optimistic about the prospects for this type of research: “For the foreseeable future, I believe the pharmaceutical industry is going to view this whole area as radioactive and stay away from it.”

He does, however, think that this kind of research is necessary. “We need to think about this finding in the context of risks and benefits. So, paradoxically, now is the time that we need more information about what are the benefits of SSRIs in kids,” he said.

Future research should focus on which subgroups of patients are at higher risk and when in the course of treatment they are at higher risk. One strategy would be to monitor depressed children closely for short periods of SSRI therapy, looking for somatic subjective dysphoria, changes in attention, changes in impulsivity, or other indicators of suicidality, Dr. Olfson said.

It's also important to look at the bigger public health picture, Dr. Olfson said. “We need to be clear about the distinctions between suicidal ideation and the suicide attempts that were the subject of the randomized controlled trials analyses and actual suicide or serial suicide attempts that we encounter in practice.”

The rates of suicidal ideation and suicide attempts in a normal adolescent population also need to be considered. According to the Centers for Disease Control and Prevention's 2003 National Youth Risk Behavior Survey, 16.9% of normal adolescents in grades 9-12 had seriously considered attempting suicide in the previous 12 months and 8.5% had attempted suicide at least once in that time period.

Those numbers stand in sharp contrast to the comparatively small number of kids who show up in emergency rooms and hospitals after actual suicide attempts, Dr. Olfson said.

WASHINGTON – It is important to balance risks with benefits when considering a selective serotonin reuptake inhibitor to treat a child or adolescent, several experts said at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The session came soon after the Food and Drug Administration's decision to require pharmaceutical companies to add a black box warning alerting prescribers to the risk of suicidal behavior with antidepressants in pediatric patients.

“I think this is very important. This is not a contraindication. This [warning] box is not telling clinicians that they can't use these drugs. What it's saying is that if a clinician is considering using an antidepressant in a child or adolescent, they need to consider the risk and balance that against the clinical need,” said Thomas Laughren, M.D., of the FDA's division of neuropharmacological drug products, Rockville, Md.

Selective serotonin reuptake inhibitors (SSRIs) do appear to work better than placebo in the short-term therapy of depression in children and adolescents, said Neal Ryan, M.D., of the Western Psychiatric Institute and Clinic in Pittsburgh. This is probably true in general, though fluoxetine is the only one with an indication for children.

Combining an SSRI with cognitive-behavioral therapy (CBT) might even be more effective, according to recent findings. In the Treatment for Adolescents With Depression Study (TADS), SSRIs combined with CBT showed the best results for treating depression. The results also suggested that pharmacotherapy is more effective than psychotherapy alone, but this finding needs to be duplicated in other studies, Dr. Ryan said.

For clinicians, the real problem is how to balance the increased short-term risk–an extra 2 per 100 patients who will either attempt suicide or exhibit suicidality because of the use of an SSRI–and the potentially decreased long-term risk of suicidal thoughts and behavior attributable to depression, Dr. Ryan said.

Clinicians are left with the dilemma of what to do about the next depressed child to come into the office: Pick an SSRI alone, choose psychotherapy alone, or combine an SSRI with psychotherapy. “I think we're going to have a rich debate on that,” Dr. Ryan said.

When considering an SSRI in a pediatric patient, it's important to inform the family of the potential risks and benefits and follow the FDA's monitoring suggestions. “I think also that we need to advocate for more studies. I think we're all scared that we won't get any more data on this question,” he said.

Mark Olfson, M.D., of Columbia University, New York, is not optimistic about the prospects for this type of research: “For the foreseeable future, I believe the pharmaceutical industry is going to view this whole area as radioactive and stay away from it.”

He does, however, think that this kind of research is necessary. “We need to think about this finding in the context of risks and benefits. So, paradoxically, now is the time that we need more information about what are the benefits of SSRIs in kids,” he said.

Future research should focus on which subgroups of patients are at higher risk and when in the course of treatment they are at higher risk. One strategy would be to monitor depressed children closely for short periods of SSRI therapy, looking for somatic subjective dysphoria, changes in attention, changes in impulsivity, or other indicators of suicidality, Dr. Olfson said.

It's also important to look at the bigger public health picture, Dr. Olfson said. “We need to be clear about the distinctions between suicidal ideation and the suicide attempts that were the subject of the randomized controlled trials analyses and actual suicide or serial suicide attempts that we encounter in practice.”

The rates of suicidal ideation and suicide attempts in a normal adolescent population also need to be considered. According to the Centers for Disease Control and Prevention's 2003 National Youth Risk Behavior Survey, 16.9% of normal adolescents in grades 9-12 had seriously considered attempting suicide in the previous 12 months and 8.5% had attempted suicide at least once in that time period.

Those numbers stand in sharp contrast to the comparatively small number of kids who show up in emergency rooms and hospitals after actual suicide attempts, Dr. Olfson said.