Kerri Wachter

WASHINGTON—An outbreak of methicillin-resistant Staphylococcus aureus in a Spanish hospital may be the first reported appearance of a linezolid-resistant strain of the organism.

Between April and June of this year, 12 patients in an intensive care unit at the Hospital Clinico San Carlos in Madrid were identified as having methicillin-resistant Staphylococcus aureus (MRSA) that was also resistant to linezolid (Zyvox). Dr. Miguel Sanchez, an internist at the hospital, reported the outbreak during a press briefing at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

Linezolid-resistant MRSA was identified during surveillance and/or diagnostic culture from eight men and four women in the ICU—eight patients were critically ill, three were surgical cases, and one was a trauma patient. LR-MRSA caused infection in 11 patients—5 with ventilator-associated pneumonia, 5 with primary bacteremia, and 1 with catheter-related sepsis.

Five patients died, but they had cleared the infection at the time of death. No deaths were attributed to LR-MRSA.

Patients had a mean ICU stay of roughly a month (34 days) before the index culture. At the index culture, all patients were intubated, had been on prolonged broad-spectrum antibiotic therapy, and had concomitant linezolid-susceptible MRSA. Eleven of the patients had received intravenous linezolid, one of the oxazolidinone class of antibiotics.

Hospital staff members were able to quickly control the outbreak by stepping up routine surveillance and isolating these patients. Patients identified with LR-MRSA were sampled once a week at three different sites.

Surveillance of the environment and staff also was performed. Only 1 of 91 environmental surface samples tested positive for LR-MRSA.

This sample was from an intravenous catheter connection. The hands of health care personnel also were sampled, and none was positive for LR-MRSA. Genotyping revealed that one clone was responsible for 10 infections.

As a result of the outbreak, hospital personnel reviewed their antibiotic use. Subsequent use of linezolid was limited to either documented or suspected cases of respiratory tract MRSA infections.

As a result, use of linezolid at the hospital dropped from 202 defined daily doses in April to 25 in July. The LR-MRSA was susceptible to vancomycin, daptomycin (Cubicin), and tigecycline (Tygacil), which were used to treat these patients. For comparison, the minimum inhibitory concentration was greater than 8 mg/L for linezolid but less than 0.32 mg/L for tigecycline and daptomycin.

“Linezolid is a relatively new drug,” noted Dr. Robert S. Daum, a pediatric infectious diseases specialist at the University of Chicago who spoke at the press conference but was not involved with the Spanish outbreak. “In general, resistance has been very infrequent. We've seen some in Chicago … but it's actually quite rare in this country.”

He attributed this to antibiotic stewardship programs at many U.S. hospitals. “In our hospital, we have a very tight grip on linezolid use.”

The drug can be prescribed only with the approval of an infectious disease specialist.

Limiting use of the drug limits the chances for an organism to develop resistance to it.

Dr. Sanchez agreed, noting that “the take-home message for us is that we have to find ways to administer antibiotics prudently. … We also have to find ways to shorten antibiotic courses.”

Dr. Sanchez and his colleagues are planning a case-control study to investigate the means of LR-MRSA transmission.

Dr. Sanchez did not report whether he had any conflicts of interest.

WASHINGTON—An outbreak of methicillin-resistant Staphylococcus aureus in a Spanish hospital may be the first reported appearance of a linezolid-resistant strain of the organism.

Between April and June of this year, 12 patients in an intensive care unit at the Hospital Clinico San Carlos in Madrid were identified as having methicillin-resistant Staphylococcus aureus (MRSA) that was also resistant to linezolid (Zyvox). Dr. Miguel Sanchez, an internist at the hospital, reported the outbreak during a press briefing at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

Linezolid-resistant MRSA was identified during surveillance and/or diagnostic culture from eight men and four women in the ICU—eight patients were critically ill, three were surgical cases, and one was a trauma patient. LR-MRSA caused infection in 11 patients—5 with ventilator-associated pneumonia, 5 with primary bacteremia, and 1 with catheter-related sepsis.

Five patients died, but they had cleared the infection at the time of death. No deaths were attributed to LR-MRSA.

Patients had a mean ICU stay of roughly a month (34 days) before the index culture. At the index culture, all patients were intubated, had been on prolonged broad-spectrum antibiotic therapy, and had concomitant linezolid-susceptible MRSA. Eleven of the patients had received intravenous linezolid, one of the oxazolidinone class of antibiotics.

Hospital staff members were able to quickly control the outbreak by stepping up routine surveillance and isolating these patients. Patients identified with LR-MRSA were sampled once a week at three different sites.

Surveillance of the environment and staff also was performed. Only 1 of 91 environmental surface samples tested positive for LR-MRSA.

This sample was from an intravenous catheter connection. The hands of health care personnel also were sampled, and none was positive for LR-MRSA. Genotyping revealed that one clone was responsible for 10 infections.

As a result of the outbreak, hospital personnel reviewed their antibiotic use. Subsequent use of linezolid was limited to either documented or suspected cases of respiratory tract MRSA infections.

As a result, use of linezolid at the hospital dropped from 202 defined daily doses in April to 25 in July. The LR-MRSA was susceptible to vancomycin, daptomycin (Cubicin), and tigecycline (Tygacil), which were used to treat these patients. For comparison, the minimum inhibitory concentration was greater than 8 mg/L for linezolid but less than 0.32 mg/L for tigecycline and daptomycin.

“Linezolid is a relatively new drug,” noted Dr. Robert S. Daum, a pediatric infectious diseases specialist at the University of Chicago who spoke at the press conference but was not involved with the Spanish outbreak. “In general, resistance has been very infrequent. We've seen some in Chicago … but it's actually quite rare in this country.”

He attributed this to antibiotic stewardship programs at many U.S. hospitals. “In our hospital, we have a very tight grip on linezolid use.”

The drug can be prescribed only with the approval of an infectious disease specialist.

Limiting use of the drug limits the chances for an organism to develop resistance to it.

Dr. Sanchez agreed, noting that “the take-home message for us is that we have to find ways to administer antibiotics prudently. … We also have to find ways to shorten antibiotic courses.”

Dr. Sanchez and his colleagues are planning a case-control study to investigate the means of LR-MRSA transmission.

Dr. Sanchez did not report whether he had any conflicts of interest.

WASHINGTON—An outbreak of methicillin-resistant Staphylococcus aureus in a Spanish hospital may be the first reported appearance of a linezolid-resistant strain of the organism.

Between April and June of this year, 12 patients in an intensive care unit at the Hospital Clinico San Carlos in Madrid were identified as having methicillin-resistant Staphylococcus aureus (MRSA) that was also resistant to linezolid (Zyvox). Dr. Miguel Sanchez, an internist at the hospital, reported the outbreak during a press briefing at the jointly held annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the annual meeting of the Infectious Diseases Society of America (IDSA).

Linezolid-resistant MRSA was identified during surveillance and/or diagnostic culture from eight men and four women in the ICU—eight patients were critically ill, three were surgical cases, and one was a trauma patient. LR-MRSA caused infection in 11 patients—5 with ventilator-associated pneumonia, 5 with primary bacteremia, and 1 with catheter-related sepsis.

Five patients died, but they had cleared the infection at the time of death. No deaths were attributed to LR-MRSA.

Patients had a mean ICU stay of roughly a month (34 days) before the index culture. At the index culture, all patients were intubated, had been on prolonged broad-spectrum antibiotic therapy, and had concomitant linezolid-susceptible MRSA. Eleven of the patients had received intravenous linezolid, one of the oxazolidinone class of antibiotics.

Hospital staff members were able to quickly control the outbreak by stepping up routine surveillance and isolating these patients. Patients identified with LR-MRSA were sampled once a week at three different sites.

Surveillance of the environment and staff also was performed. Only 1 of 91 environmental surface samples tested positive for LR-MRSA.

This sample was from an intravenous catheter connection. The hands of health care personnel also were sampled, and none was positive for LR-MRSA. Genotyping revealed that one clone was responsible for 10 infections.

As a result of the outbreak, hospital personnel reviewed their antibiotic use. Subsequent use of linezolid was limited to either documented or suspected cases of respiratory tract MRSA infections.

As a result, use of linezolid at the hospital dropped from 202 defined daily doses in April to 25 in July. The LR-MRSA was susceptible to vancomycin, daptomycin (Cubicin), and tigecycline (Tygacil), which were used to treat these patients. For comparison, the minimum inhibitory concentration was greater than 8 mg/L for linezolid but less than 0.32 mg/L for tigecycline and daptomycin.

“Linezolid is a relatively new drug,” noted Dr. Robert S. Daum, a pediatric infectious diseases specialist at the University of Chicago who spoke at the press conference but was not involved with the Spanish outbreak. “In general, resistance has been very infrequent. We've seen some in Chicago … but it's actually quite rare in this country.”

He attributed this to antibiotic stewardship programs at many U.S. hospitals. “In our hospital, we have a very tight grip on linezolid use.”

The drug can be prescribed only with the approval of an infectious disease specialist.

Limiting use of the drug limits the chances for an organism to develop resistance to it.

Dr. Sanchez agreed, noting that “the take-home message for us is that we have to find ways to administer antibiotics prudently. … We also have to find ways to shorten antibiotic courses.”

Dr. Sanchez and his colleagues are planning a case-control study to investigate the means of LR-MRSA transmission.

Dr. Sanchez did not report whether he had any conflicts of interest.

Optical coherence tomography is a technique that has been used to measure the thickness of the retinal nerve fiber layer and macular volume in glaucoma and other retinal diseases. These measurements provide information about the thickness of axons that emanate from the retinal ganglion cell bodies, which coalesce in the optic nerve.

Optical coherence tomography (OCT) uses infrared (IR) light to measure the thickness of the nerves in the back of the retina. The light is bounced off the retina; the way it is reflected back to a recorder at a particular point is used to develop images of the thickness of layers of the tissue at the back of the eye.

This is similar to the way ultrasound works. “It's light-based instead of sound-based,” said Dr. Peter Calabresi, director of the Multiple Sclerosis Center at Johns Hopkins University, Baltimore.

The depth of penetrance for the IR light is fairly shallow, which makes it a good technique for looking at structures and tissues right below the surface. With the latest generation of instruments, resolution is down to about 3–4 micrometers, which provides “almost a microscopic picture of the eye,” said Dr. Calabresi.

Dr. Calabresi and his colleagues have been using OCT to assess disease status in patients with multiple sclerosis. Because the retinal nerves coalesce into the optic nerve, “We know with MS that if you injure nerves in one location, that you will see downstream consequences.” Neurologists have long looked at the optic nerve head to see if it looks pale in color to determine whether the patient may have had an optic neuritis attack that led to some injury of the nerves at the back of the eye.

The retinal nerve fiber layer (RNFL) has been described as atrophying in focal/segmental patterns after an optic neuritis attack, which suggests that there were small areas of injury rather than a diffuse global process. OCT allows researchers to quantify these focal/segmental patterns of atrophy in the retinal nerve fiber layer. “This just allows us now to quantify it and to have a reproducible and reliable objective measure.”

In one study published by Dr. Calabresi and his colleagues, they compared OCT findings of the RNFL between a large cohort of MS patients and a group of healthy controls (Neurology 2007;69:2085–92). In this study, patients with MS had abnormal RNFL findings, even if they didn't have a history of optic neuritis. OCT “could then be used as a diagnostic tool to then pick up subclinical disease,” Dr. Calabresi said.

In another study, the researchers were able to show that changes in the RNFL were correlated with global brain atrophy in MS patients (Neurology 2007;69:1603–9). “By looking at this one part of the nervous system, it may be predictive of what's happening in the rest of the brain,” Dr. Calabresi said.

In the third study, they showed that the technique provides intrarater and interrater reproducibility (Arch. Neurol. 2008;65:1218–22), which is important because MS patients produce unique challenges for OCT. “Although other people have reported this in the ophthalmology world, we thought it was important to show [that] you could do this in a neurology office with MS patients,” he said. “I think it was important to show that in a patient with a more diffuse global disease, that we could get them to hold still enough to do the testing.”

There are a few caveats about OCT to consider. “The abnormalities that we look at on OCT are not specific to MS. It's very important to rule out glaucoma and other retinal processes related to hypertension or diabetes,” Dr. Calabresi said. Once a neurologist is fairly certain that the retinal abnormalities are related to MS, “it's a very useful way of tracking the disease,” said Dr. Calabresi.

OCT has some advantages over MRI—it's an office-based technique that takes about 10 minutes to perform and is much cheaper and more user-friendly than MRI. Despite this, OCT will not likely take the place of brain imaging. Dr. Calabresi sees OCT as useful in partnership with MRI.

“I imagine using it frequently in the office when the patient is coming in for a visit to directly assess the eyes and to give you some information about the status of the retinal nerves.

“We know the progressive cases tend to have more [RNFL] damage and we know that it is somewhat predictive of what is happening in the brain.”

The technique could be used in the period between brain imaging scans to assess progression.

As yet, there are no longitudinal data on the use of OCT to track progression, said Dr. Calabresi.

“What everyone wants to know is how quickly does this measurement change?” In the studies to date, patients have had their disease for about 8–10 years, and there is only about a 10-micrometer difference in RNFL thickness between MS patients and controls.

If RNFL thickness changes at a steady rate, this translates to about a micrometer per year—which falls within the margin of error. However, longitudinal data may show periods of more rapid progression and periods of relative stability, said Dr. Calabresi.

“What we're finding in OCT is that over a 2-year period, 10%-15% of people have stepwise declines of up to 10 micrometers … It's not that everyone is just losing a little bit. Some people will have subclinical attacks and not necessarily even know that they had an optic neuritis episode.”

Dr. Calabresi and his colleagues are currently working on a longitudinal study of about 1,000 patients that they've been tracking. The results are expected in the next year.

OCT is already showing promise in the clinical trial setting, where it could be used at frequent intervals to track the effectiveness of a drug on halting MS progression. The technique is being used in optic neuritis drug trials, and several companies are interested in using OCT as an assessment tool in MS trials.

Dr. Calabresi reported that he does not have any relevant conflicts of interest.

RNFL thickness map shows the right eye of an MS patient.

Areas of Red and yellow show areas of abnormality.

RNFL thickness (black line) for 0–360 degrees in right eye (top): Bottom image is a tomogram of the right eye's RNFL. Images courtesy Dr. Peter Calabresi

Optical coherence tomography is a technique that has been used to measure the thickness of the retinal nerve fiber layer and macular volume in glaucoma and other retinal diseases. These measurements provide information about the thickness of axons that emanate from the retinal ganglion cell bodies, which coalesce in the optic nerve.

Optical coherence tomography (OCT) uses infrared (IR) light to measure the thickness of the nerves in the back of the retina. The light is bounced off the retina; the way it is reflected back to a recorder at a particular point is used to develop images of the thickness of layers of the tissue at the back of the eye.

This is similar to the way ultrasound works. “It's light-based instead of sound-based,” said Dr. Peter Calabresi, director of the Multiple Sclerosis Center at Johns Hopkins University, Baltimore.

The depth of penetrance for the IR light is fairly shallow, which makes it a good technique for looking at structures and tissues right below the surface. With the latest generation of instruments, resolution is down to about 3–4 micrometers, which provides “almost a microscopic picture of the eye,” said Dr. Calabresi.

Dr. Calabresi and his colleagues have been using OCT to assess disease status in patients with multiple sclerosis. Because the retinal nerves coalesce into the optic nerve, “We know with MS that if you injure nerves in one location, that you will see downstream consequences.” Neurologists have long looked at the optic nerve head to see if it looks pale in color to determine whether the patient may have had an optic neuritis attack that led to some injury of the nerves at the back of the eye.

The retinal nerve fiber layer (RNFL) has been described as atrophying in focal/segmental patterns after an optic neuritis attack, which suggests that there were small areas of injury rather than a diffuse global process. OCT allows researchers to quantify these focal/segmental patterns of atrophy in the retinal nerve fiber layer. “This just allows us now to quantify it and to have a reproducible and reliable objective measure.”

In one study published by Dr. Calabresi and his colleagues, they compared OCT findings of the RNFL between a large cohort of MS patients and a group of healthy controls (Neurology 2007;69:2085–92). In this study, patients with MS had abnormal RNFL findings, even if they didn't have a history of optic neuritis. OCT “could then be used as a diagnostic tool to then pick up subclinical disease,” Dr. Calabresi said.

In another study, the researchers were able to show that changes in the RNFL were correlated with global brain atrophy in MS patients (Neurology 2007;69:1603–9). “By looking at this one part of the nervous system, it may be predictive of what's happening in the rest of the brain,” Dr. Calabresi said.

In the third study, they showed that the technique provides intrarater and interrater reproducibility (Arch. Neurol. 2008;65:1218–22), which is important because MS patients produce unique challenges for OCT. “Although other people have reported this in the ophthalmology world, we thought it was important to show [that] you could do this in a neurology office with MS patients,” he said. “I think it was important to show that in a patient with a more diffuse global disease, that we could get them to hold still enough to do the testing.”

There are a few caveats about OCT to consider. “The abnormalities that we look at on OCT are not specific to MS. It's very important to rule out glaucoma and other retinal processes related to hypertension or diabetes,” Dr. Calabresi said. Once a neurologist is fairly certain that the retinal abnormalities are related to MS, “it's a very useful way of tracking the disease,” said Dr. Calabresi.

OCT has some advantages over MRI—it's an office-based technique that takes about 10 minutes to perform and is much cheaper and more user-friendly than MRI. Despite this, OCT will not likely take the place of brain imaging. Dr. Calabresi sees OCT as useful in partnership with MRI.

“I imagine using it frequently in the office when the patient is coming in for a visit to directly assess the eyes and to give you some information about the status of the retinal nerves.

“We know the progressive cases tend to have more [RNFL] damage and we know that it is somewhat predictive of what is happening in the brain.”

The technique could be used in the period between brain imaging scans to assess progression.

As yet, there are no longitudinal data on the use of OCT to track progression, said Dr. Calabresi.

“What everyone wants to know is how quickly does this measurement change?” In the studies to date, patients have had their disease for about 8–10 years, and there is only about a 10-micrometer difference in RNFL thickness between MS patients and controls.

If RNFL thickness changes at a steady rate, this translates to about a micrometer per year—which falls within the margin of error. However, longitudinal data may show periods of more rapid progression and periods of relative stability, said Dr. Calabresi.

“What we're finding in OCT is that over a 2-year period, 10%-15% of people have stepwise declines of up to 10 micrometers … It's not that everyone is just losing a little bit. Some people will have subclinical attacks and not necessarily even know that they had an optic neuritis episode.”

Dr. Calabresi and his colleagues are currently working on a longitudinal study of about 1,000 patients that they've been tracking. The results are expected in the next year.

OCT is already showing promise in the clinical trial setting, where it could be used at frequent intervals to track the effectiveness of a drug on halting MS progression. The technique is being used in optic neuritis drug trials, and several companies are interested in using OCT as an assessment tool in MS trials.

Dr. Calabresi reported that he does not have any relevant conflicts of interest.

RNFL thickness map shows the right eye of an MS patient.

Areas of Red and yellow show areas of abnormality.

RNFL thickness (black line) for 0–360 degrees in right eye (top): Bottom image is a tomogram of the right eye's RNFL. Images courtesy Dr. Peter Calabresi

Optical coherence tomography is a technique that has been used to measure the thickness of the retinal nerve fiber layer and macular volume in glaucoma and other retinal diseases. These measurements provide information about the thickness of axons that emanate from the retinal ganglion cell bodies, which coalesce in the optic nerve.

Optical coherence tomography (OCT) uses infrared (IR) light to measure the thickness of the nerves in the back of the retina. The light is bounced off the retina; the way it is reflected back to a recorder at a particular point is used to develop images of the thickness of layers of the tissue at the back of the eye.

This is similar to the way ultrasound works. “It's light-based instead of sound-based,” said Dr. Peter Calabresi, director of the Multiple Sclerosis Center at Johns Hopkins University, Baltimore.

The depth of penetrance for the IR light is fairly shallow, which makes it a good technique for looking at structures and tissues right below the surface. With the latest generation of instruments, resolution is down to about 3–4 micrometers, which provides “almost a microscopic picture of the eye,” said Dr. Calabresi.

Dr. Calabresi and his colleagues have been using OCT to assess disease status in patients with multiple sclerosis. Because the retinal nerves coalesce into the optic nerve, “We know with MS that if you injure nerves in one location, that you will see downstream consequences.” Neurologists have long looked at the optic nerve head to see if it looks pale in color to determine whether the patient may have had an optic neuritis attack that led to some injury of the nerves at the back of the eye.

The retinal nerve fiber layer (RNFL) has been described as atrophying in focal/segmental patterns after an optic neuritis attack, which suggests that there were small areas of injury rather than a diffuse global process. OCT allows researchers to quantify these focal/segmental patterns of atrophy in the retinal nerve fiber layer. “This just allows us now to quantify it and to have a reproducible and reliable objective measure.”

In one study published by Dr. Calabresi and his colleagues, they compared OCT findings of the RNFL between a large cohort of MS patients and a group of healthy controls (Neurology 2007;69:2085–92). In this study, patients with MS had abnormal RNFL findings, even if they didn't have a history of optic neuritis. OCT “could then be used as a diagnostic tool to then pick up subclinical disease,” Dr. Calabresi said.

In another study, the researchers were able to show that changes in the RNFL were correlated with global brain atrophy in MS patients (Neurology 2007;69:1603–9). “By looking at this one part of the nervous system, it may be predictive of what's happening in the rest of the brain,” Dr. Calabresi said.

In the third study, they showed that the technique provides intrarater and interrater reproducibility (Arch. Neurol. 2008;65:1218–22), which is important because MS patients produce unique challenges for OCT. “Although other people have reported this in the ophthalmology world, we thought it was important to show [that] you could do this in a neurology office with MS patients,” he said. “I think it was important to show that in a patient with a more diffuse global disease, that we could get them to hold still enough to do the testing.”

There are a few caveats about OCT to consider. “The abnormalities that we look at on OCT are not specific to MS. It's very important to rule out glaucoma and other retinal processes related to hypertension or diabetes,” Dr. Calabresi said. Once a neurologist is fairly certain that the retinal abnormalities are related to MS, “it's a very useful way of tracking the disease,” said Dr. Calabresi.

OCT has some advantages over MRI—it's an office-based technique that takes about 10 minutes to perform and is much cheaper and more user-friendly than MRI. Despite this, OCT will not likely take the place of brain imaging. Dr. Calabresi sees OCT as useful in partnership with MRI.

“I imagine using it frequently in the office when the patient is coming in for a visit to directly assess the eyes and to give you some information about the status of the retinal nerves.

“We know the progressive cases tend to have more [RNFL] damage and we know that it is somewhat predictive of what is happening in the brain.”

The technique could be used in the period between brain imaging scans to assess progression.

As yet, there are no longitudinal data on the use of OCT to track progression, said Dr. Calabresi.

“What everyone wants to know is how quickly does this measurement change?” In the studies to date, patients have had their disease for about 8–10 years, and there is only about a 10-micrometer difference in RNFL thickness between MS patients and controls.

If RNFL thickness changes at a steady rate, this translates to about a micrometer per year—which falls within the margin of error. However, longitudinal data may show periods of more rapid progression and periods of relative stability, said Dr. Calabresi.

“What we're finding in OCT is that over a 2-year period, 10%-15% of people have stepwise declines of up to 10 micrometers … It's not that everyone is just losing a little bit. Some people will have subclinical attacks and not necessarily even know that they had an optic neuritis episode.”

Dr. Calabresi and his colleagues are currently working on a longitudinal study of about 1,000 patients that they've been tracking. The results are expected in the next year.

OCT is already showing promise in the clinical trial setting, where it could be used at frequent intervals to track the effectiveness of a drug on halting MS progression. The technique is being used in optic neuritis drug trials, and several companies are interested in using OCT as an assessment tool in MS trials.

Dr. Calabresi reported that he does not have any relevant conflicts of interest.

RNFL thickness map shows the right eye of an MS patient.

Areas of Red and yellow show areas of abnormality.

RNFL thickness (black line) for 0–360 degrees in right eye (top): Bottom image is a tomogram of the right eye's RNFL. Images courtesy Dr. Peter Calabresi

A new genetic risk score for gout, based on three recently identified genes believed to be involved in renal urate transportation, could help physicians identify patients with asymptomatic hyperuricemia and guide therapy, according to a study reported online in the Lancet on the Oct. 1.

“Our genetic risk score was associated with up to 40-fold increased risk of developing gout, which is substantially higher than for environmental risk factors, suggesting that knowledge of genotype could help identify individuals at risk of developing gout long before the onset of clinical features of the disease,” wrote Dr. Abbas Dehghan of the Erasmus Medical Center in Rotterdam, the Netherlands, and coauthors from both the United States and the Netherlands (Lancet 2008 Oct. 1[doi:10.1016/S0140-6736(08)613-4]).

The researchers used phenotype and genotype results from a cohort of the Framingham Heart Study and a Rotterdam cohort to identify genetic loci associated with uric acid concentration and then replicated the findings in a third population-based study, the Atherosclerosis Risk in Communities (ARIC) study. The single nucleotide polymorphisms (SNPs) they identified as being associated with uric acid concentration were tested next for association with gout. These results were then replicated using genetic samples from the ARIC study. Finally, they developed the additive gout risk score of high-risk alleles at the three loci identified.

The researchers identified two new loci, ABCG2 and SLC17A3, that show an association with uric acid concentration and risk of gout. In addition, they confirmed the previously reported association of SLC2A9 with uric acid and gout in white individuals and extended the findings to black individuals.

The Framingham cohort study involved three generations of participants, who underwent examinations every 2 years to identify cardiovascular diseases and their risk factors. Almost all were self-identified as white. The Rotterdam cohort study is a prospective, population-based study of determinants of several chronic diseases in individuals older than 5 years. All participants were residents of the Ommoord district of Rotterdam and underwent periodic examination. ARIC is an ongoing population-based study in four U.S. communities. White and black participants aged 45–64 years were recruited and underwent examination roughly every 3 years.

In the Framingham cohort, uric acid concentration was measured at the first examination cycle. Gout was self-reported in the offspring and third-generation cohorts. In the Rotterdam cohort, uric acid concentration was measured at baseline. Individuals treated with drugs exclusively prescribed for gout were regarded as gout patients, based on pharmacy records. In the ARIC study, uric acid concentration was measured at visit one. Gout was identified by self-report at visit 4.

Genotyping of the Framingham cohort was performed for 9,274 participants, and the final sample size was 7,699. Genotyping for the Rotterdam cohort was done for 6,680 participants, with a final sample size was 5,974.

In the ARIC study, the central DNA laboratory genotyped SNPs rs16890979, rs2231142, and rs1165205 individually for 11,024 white participants and 3,843 black participants.

SNPs in SLC2A9 have previously been identified as having an association with uric acid concentration and were connected with low renal fractional excretion of uric acid (the most common cause of hyperuricemia). Three loci had SNPs that reached genome-wide significance in the Framingham cohort. For each locus, the most significant SNPs were rs16890979 (a missense SNP in SLC2A9), rs2231142 (a missense SNP in ABCG2), and rs1165205 (intron 1 of SLC17A3). Similarly, two loci showed genome-wide significance in the Rotterdam cohort: rs6449213 (intron 4 of SLC2A9) and rs2231142.

Both rs6449213 and rs2231142 were strongly associated with uric acid concentration in white and black participants; rs1165205 was strongly associated with uric acid in white participants only. The missense SNP rs16890979 in SLC2A9 has the strongest association with uric acid concentration and gout. In addition, rs16890979 explained the largest variation in uric acid concentration, ranging from 2.8% to 5.3% in white participants across studies; rs16890979 was associated with gout in white individuals from all three studies. Results showing significance were also seen for rs2231142, rs1165205, and rs6449213. In black individuals, only rs2231142 showed a marginal association with gout.

In the Framingham cohort, only rs2231142 remained associated with gout after adjusting for uric acid (odds ratio 1.57, P = .0053). No SNPs in the Rotterdam cohort were significant after adjustment for uric acid. Substantial attenuation of the genotypic effect for all three loci on gout risk was seen after adjustment for uric acid in the ARIC group.

A genetic risk score was generated for every individual by counting the number of alleles associated with high uric acid concentration (rs16890979 C, rs2231142 T, and rs1165205 A; range 0–6). Mean uric acid concentration increased linearly with the number of risk alleles. For individuals with no risk alleles, the crude prevalence of gout was 1%–2% across studies and increased to 8%–18% with six risk alleles. “Although individual common genetic variants confer a modest risk of gout, their combination resulted in a large association with uric acid and gout,” they wrote.

The study was funded by the Netherlands Organisation for Scientific Research and the National Heart, Lung, and Blood Institute. The authors reported that they had no conflicts of interest.

A new genetic risk score for gout, based on three recently identified genes believed to be involved in renal urate transportation, could help physicians identify patients with asymptomatic hyperuricemia and guide therapy, according to a study reported online in the Lancet on the Oct. 1.

“Our genetic risk score was associated with up to 40-fold increased risk of developing gout, which is substantially higher than for environmental risk factors, suggesting that knowledge of genotype could help identify individuals at risk of developing gout long before the onset of clinical features of the disease,” wrote Dr. Abbas Dehghan of the Erasmus Medical Center in Rotterdam, the Netherlands, and coauthors from both the United States and the Netherlands (Lancet 2008 Oct. 1[doi:10.1016/S0140-6736(08)613-4]).

The researchers used phenotype and genotype results from a cohort of the Framingham Heart Study and a Rotterdam cohort to identify genetic loci associated with uric acid concentration and then replicated the findings in a third population-based study, the Atherosclerosis Risk in Communities (ARIC) study. The single nucleotide polymorphisms (SNPs) they identified as being associated with uric acid concentration were tested next for association with gout. These results were then replicated using genetic samples from the ARIC study. Finally, they developed the additive gout risk score of high-risk alleles at the three loci identified.

The researchers identified two new loci, ABCG2 and SLC17A3, that show an association with uric acid concentration and risk of gout. In addition, they confirmed the previously reported association of SLC2A9 with uric acid and gout in white individuals and extended the findings to black individuals.

The Framingham cohort study involved three generations of participants, who underwent examinations every 2 years to identify cardiovascular diseases and their risk factors. Almost all were self-identified as white. The Rotterdam cohort study is a prospective, population-based study of determinants of several chronic diseases in individuals older than 5 years. All participants were residents of the Ommoord district of Rotterdam and underwent periodic examination. ARIC is an ongoing population-based study in four U.S. communities. White and black participants aged 45–64 years were recruited and underwent examination roughly every 3 years.

In the Framingham cohort, uric acid concentration was measured at the first examination cycle. Gout was self-reported in the offspring and third-generation cohorts. In the Rotterdam cohort, uric acid concentration was measured at baseline. Individuals treated with drugs exclusively prescribed for gout were regarded as gout patients, based on pharmacy records. In the ARIC study, uric acid concentration was measured at visit one. Gout was identified by self-report at visit 4.

Genotyping of the Framingham cohort was performed for 9,274 participants, and the final sample size was 7,699. Genotyping for the Rotterdam cohort was done for 6,680 participants, with a final sample size was 5,974.

In the ARIC study, the central DNA laboratory genotyped SNPs rs16890979, rs2231142, and rs1165205 individually for 11,024 white participants and 3,843 black participants.

SNPs in SLC2A9 have previously been identified as having an association with uric acid concentration and were connected with low renal fractional excretion of uric acid (the most common cause of hyperuricemia). Three loci had SNPs that reached genome-wide significance in the Framingham cohort. For each locus, the most significant SNPs were rs16890979 (a missense SNP in SLC2A9), rs2231142 (a missense SNP in ABCG2), and rs1165205 (intron 1 of SLC17A3). Similarly, two loci showed genome-wide significance in the Rotterdam cohort: rs6449213 (intron 4 of SLC2A9) and rs2231142.

Both rs6449213 and rs2231142 were strongly associated with uric acid concentration in white and black participants; rs1165205 was strongly associated with uric acid in white participants only. The missense SNP rs16890979 in SLC2A9 has the strongest association with uric acid concentration and gout. In addition, rs16890979 explained the largest variation in uric acid concentration, ranging from 2.8% to 5.3% in white participants across studies; rs16890979 was associated with gout in white individuals from all three studies. Results showing significance were also seen for rs2231142, rs1165205, and rs6449213. In black individuals, only rs2231142 showed a marginal association with gout.

In the Framingham cohort, only rs2231142 remained associated with gout after adjusting for uric acid (odds ratio 1.57, P = .0053). No SNPs in the Rotterdam cohort were significant after adjustment for uric acid. Substantial attenuation of the genotypic effect for all three loci on gout risk was seen after adjustment for uric acid in the ARIC group.

A genetic risk score was generated for every individual by counting the number of alleles associated with high uric acid concentration (rs16890979 C, rs2231142 T, and rs1165205 A; range 0–6). Mean uric acid concentration increased linearly with the number of risk alleles. For individuals with no risk alleles, the crude prevalence of gout was 1%–2% across studies and increased to 8%–18% with six risk alleles. “Although individual common genetic variants confer a modest risk of gout, their combination resulted in a large association with uric acid and gout,” they wrote.

The study was funded by the Netherlands Organisation for Scientific Research and the National Heart, Lung, and Blood Institute. The authors reported that they had no conflicts of interest.

A new genetic risk score for gout, based on three recently identified genes believed to be involved in renal urate transportation, could help physicians identify patients with asymptomatic hyperuricemia and guide therapy, according to a study reported online in the Lancet on the Oct. 1.

“Our genetic risk score was associated with up to 40-fold increased risk of developing gout, which is substantially higher than for environmental risk factors, suggesting that knowledge of genotype could help identify individuals at risk of developing gout long before the onset of clinical features of the disease,” wrote Dr. Abbas Dehghan of the Erasmus Medical Center in Rotterdam, the Netherlands, and coauthors from both the United States and the Netherlands (Lancet 2008 Oct. 1[doi:10.1016/S0140-6736(08)613-4]).

The researchers used phenotype and genotype results from a cohort of the Framingham Heart Study and a Rotterdam cohort to identify genetic loci associated with uric acid concentration and then replicated the findings in a third population-based study, the Atherosclerosis Risk in Communities (ARIC) study. The single nucleotide polymorphisms (SNPs) they identified as being associated with uric acid concentration were tested next for association with gout. These results were then replicated using genetic samples from the ARIC study. Finally, they developed the additive gout risk score of high-risk alleles at the three loci identified.

The researchers identified two new loci, ABCG2 and SLC17A3, that show an association with uric acid concentration and risk of gout. In addition, they confirmed the previously reported association of SLC2A9 with uric acid and gout in white individuals and extended the findings to black individuals.

The Framingham cohort study involved three generations of participants, who underwent examinations every 2 years to identify cardiovascular diseases and their risk factors. Almost all were self-identified as white. The Rotterdam cohort study is a prospective, population-based study of determinants of several chronic diseases in individuals older than 5 years. All participants were residents of the Ommoord district of Rotterdam and underwent periodic examination. ARIC is an ongoing population-based study in four U.S. communities. White and black participants aged 45–64 years were recruited and underwent examination roughly every 3 years.

In the Framingham cohort, uric acid concentration was measured at the first examination cycle. Gout was self-reported in the offspring and third-generation cohorts. In the Rotterdam cohort, uric acid concentration was measured at baseline. Individuals treated with drugs exclusively prescribed for gout were regarded as gout patients, based on pharmacy records. In the ARIC study, uric acid concentration was measured at visit one. Gout was identified by self-report at visit 4.

Genotyping of the Framingham cohort was performed for 9,274 participants, and the final sample size was 7,699. Genotyping for the Rotterdam cohort was done for 6,680 participants, with a final sample size was 5,974.

In the ARIC study, the central DNA laboratory genotyped SNPs rs16890979, rs2231142, and rs1165205 individually for 11,024 white participants and 3,843 black participants.

SNPs in SLC2A9 have previously been identified as having an association with uric acid concentration and were connected with low renal fractional excretion of uric acid (the most common cause of hyperuricemia). Three loci had SNPs that reached genome-wide significance in the Framingham cohort. For each locus, the most significant SNPs were rs16890979 (a missense SNP in SLC2A9), rs2231142 (a missense SNP in ABCG2), and rs1165205 (intron 1 of SLC17A3). Similarly, two loci showed genome-wide significance in the Rotterdam cohort: rs6449213 (intron 4 of SLC2A9) and rs2231142.

Both rs6449213 and rs2231142 were strongly associated with uric acid concentration in white and black participants; rs1165205 was strongly associated with uric acid in white participants only. The missense SNP rs16890979 in SLC2A9 has the strongest association with uric acid concentration and gout. In addition, rs16890979 explained the largest variation in uric acid concentration, ranging from 2.8% to 5.3% in white participants across studies; rs16890979 was associated with gout in white individuals from all three studies. Results showing significance were also seen for rs2231142, rs1165205, and rs6449213. In black individuals, only rs2231142 showed a marginal association with gout.

In the Framingham cohort, only rs2231142 remained associated with gout after adjusting for uric acid (odds ratio 1.57, P = .0053). No SNPs in the Rotterdam cohort were significant after adjustment for uric acid. Substantial attenuation of the genotypic effect for all three loci on gout risk was seen after adjustment for uric acid in the ARIC group.

A genetic risk score was generated for every individual by counting the number of alleles associated with high uric acid concentration (rs16890979 C, rs2231142 T, and rs1165205 A; range 0–6). Mean uric acid concentration increased linearly with the number of risk alleles. For individuals with no risk alleles, the crude prevalence of gout was 1%–2% across studies and increased to 8%–18% with six risk alleles. “Although individual common genetic variants confer a modest risk of gout, their combination resulted in a large association with uric acid and gout,” they wrote.

The study was funded by the Netherlands Organisation for Scientific Research and the National Heart, Lung, and Blood Institute. The authors reported that they had no conflicts of interest.

PARIS — Patients with moderate to severe psoriasis are at increased risk for cardiovascular disorders and diabetes, which often go undiagnosed, according to an analysis of three clinical trials.

“There was a substantial number of psoriasis patients with previously undiagnosed cardiovascular risk factors in this psoriasis clinical trial population,” wrote Dr. Alexandra B. Kimball and her colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

Of 2,316 psoriasis patients, 27% had a diagnosis of hypertension at baseline; another 13% met the criteria for hypertension but were undiagnosed. Likewise, 20% had a diagnosis of hyperlipidemia at baseline; another 6% met the criteria but were undiagnosed. Last, 11% were diagnosed with diabetes at baseline; another 6% met the criteria but were undiagnosed, wrote Dr. Kimball of the department of dermatology at Harvard Medical School, Boston.

The researchers examined the medical histories of patients with moderate to severe psoriasis in one phase II and two phase III trials investigating the efficacy and safety of ustekinumab. They were enrolled in either the phase II C0379T04 trial (320), the phase III PHOENIX II trial (766), or the phase III PHOENIX III trial (1,230).

Body mass index was used to evaluate the proportion of patients who were overweight (BMI of 25–29 kg/m

Diabetes was defined by a fasting plasma glucose level of at least 7.0 mmol/L. Hypertension was defined as systolic blood pressure of at least 140 mm Hg or diastolic blood pressure of at least 90 mm Hg. Hyperlipidemia was defined as a total cholesterol level of at least 6.2 mmol/L.

Half of the patients were obese (49%) and a third (33%) were overweight. In addition, a third (32%) smoked, a quarter (27%) had hypertension, 20% had hyperlipidemia, and 11% had diabetes.

Patients with moderate to severe psoriasis were 56% more likely to be diabetic than the general U.S. population (prevalence ratio [PR], 1.6). Psoriasis patients were 50% more likely to be obese (PR, 1.5), 37% more likely to smoke (PR, 1.37), 18% more likely to be overweight (PR, 1.18), and 11% more likely to have hyperlipidemia (PR, 1.11).

The study was supported by Centocor Inc., which is developing ustekinumab. Two of Dr. Kimball's coauthors are employed by the company.

PARIS — Patients with moderate to severe psoriasis are at increased risk for cardiovascular disorders and diabetes, which often go undiagnosed, according to an analysis of three clinical trials.

“There was a substantial number of psoriasis patients with previously undiagnosed cardiovascular risk factors in this psoriasis clinical trial population,” wrote Dr. Alexandra B. Kimball and her colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

Of 2,316 psoriasis patients, 27% had a diagnosis of hypertension at baseline; another 13% met the criteria for hypertension but were undiagnosed. Likewise, 20% had a diagnosis of hyperlipidemia at baseline; another 6% met the criteria but were undiagnosed. Last, 11% were diagnosed with diabetes at baseline; another 6% met the criteria but were undiagnosed, wrote Dr. Kimball of the department of dermatology at Harvard Medical School, Boston.

The researchers examined the medical histories of patients with moderate to severe psoriasis in one phase II and two phase III trials investigating the efficacy and safety of ustekinumab. They were enrolled in either the phase II C0379T04 trial (320), the phase III PHOENIX II trial (766), or the phase III PHOENIX III trial (1,230).

Body mass index was used to evaluate the proportion of patients who were overweight (BMI of 25–29 kg/m

Diabetes was defined by a fasting plasma glucose level of at least 7.0 mmol/L. Hypertension was defined as systolic blood pressure of at least 140 mm Hg or diastolic blood pressure of at least 90 mm Hg. Hyperlipidemia was defined as a total cholesterol level of at least 6.2 mmol/L.

Half of the patients were obese (49%) and a third (33%) were overweight. In addition, a third (32%) smoked, a quarter (27%) had hypertension, 20% had hyperlipidemia, and 11% had diabetes.

Patients with moderate to severe psoriasis were 56% more likely to be diabetic than the general U.S. population (prevalence ratio [PR], 1.6). Psoriasis patients were 50% more likely to be obese (PR, 1.5), 37% more likely to smoke (PR, 1.37), 18% more likely to be overweight (PR, 1.18), and 11% more likely to have hyperlipidemia (PR, 1.11).

The study was supported by Centocor Inc., which is developing ustekinumab. Two of Dr. Kimball's coauthors are employed by the company.

PARIS — Patients with moderate to severe psoriasis are at increased risk for cardiovascular disorders and diabetes, which often go undiagnosed, according to an analysis of three clinical trials.

“There was a substantial number of psoriasis patients with previously undiagnosed cardiovascular risk factors in this psoriasis clinical trial population,” wrote Dr. Alexandra B. Kimball and her colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

Of 2,316 psoriasis patients, 27% had a diagnosis of hypertension at baseline; another 13% met the criteria for hypertension but were undiagnosed. Likewise, 20% had a diagnosis of hyperlipidemia at baseline; another 6% met the criteria but were undiagnosed. Last, 11% were diagnosed with diabetes at baseline; another 6% met the criteria but were undiagnosed, wrote Dr. Kimball of the department of dermatology at Harvard Medical School, Boston.

The researchers examined the medical histories of patients with moderate to severe psoriasis in one phase II and two phase III trials investigating the efficacy and safety of ustekinumab. They were enrolled in either the phase II C0379T04 trial (320), the phase III PHOENIX II trial (766), or the phase III PHOENIX III trial (1,230).

Body mass index was used to evaluate the proportion of patients who were overweight (BMI of 25–29 kg/m

Diabetes was defined by a fasting plasma glucose level of at least 7.0 mmol/L. Hypertension was defined as systolic blood pressure of at least 140 mm Hg or diastolic blood pressure of at least 90 mm Hg. Hyperlipidemia was defined as a total cholesterol level of at least 6.2 mmol/L.

Half of the patients were obese (49%) and a third (33%) were overweight. In addition, a third (32%) smoked, a quarter (27%) had hypertension, 20% had hyperlipidemia, and 11% had diabetes.

Patients with moderate to severe psoriasis were 56% more likely to be diabetic than the general U.S. population (prevalence ratio [PR], 1.6). Psoriasis patients were 50% more likely to be obese (PR, 1.5), 37% more likely to smoke (PR, 1.37), 18% more likely to be overweight (PR, 1.18), and 11% more likely to have hyperlipidemia (PR, 1.11).

The study was supported by Centocor Inc., which is developing ustekinumab. Two of Dr. Kimball's coauthors are employed by the company.

WASHINGTON – Children who can imagine drinking alcohol in the future may be at greater risk for early alcohol use, findings of a study of 79 children show.

The existence of a possible self who drinks alcohol might be an important predictor that mediates the effect of known precursors of alcohol problems–such as antisocial behavior and parental alcohol problems–on early alcohol use, Colleen Corte, Ph.D., and Laura Szalacha, Ed.D., hypothesized in a poster presented at a joint meeting sponsored by the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Dr. Corte and Dr. Szalacha are with the health systems science department at the University of Illinois at Chicago.

A possible self is a person's conception of who he or she will be at a future time. Previous research has shown that possible selves play a strong role in risk behaviors. In turn, risk behaviors have been shown to reinforce and strengthen possible selves.

To test this hypothesis, the researchers recruited 79 children from schools and summer youth programs. The children were an average age of 10.7 years.

To assess the ability to conceive of a future self who drank alcohol (possible drinking self), the children were asked to rate how much the phrase “drink too much alcohol” is likely to describe them in the future. Lifetime drinking was assessed using a single question: Have you ever had more than a few sips of alcohol? Those who answered yes were asked about whether their parents knew.

Almost a fifth (19%) reported a drinking possible self; 19% also reported ever drinking, but 4% reported drinking when their parents were not aware of it. Forty percent of those with a drinking possible self reported ever drinking.

WASHINGTON – Children who can imagine drinking alcohol in the future may be at greater risk for early alcohol use, findings of a study of 79 children show.

The existence of a possible self who drinks alcohol might be an important predictor that mediates the effect of known precursors of alcohol problems–such as antisocial behavior and parental alcohol problems–on early alcohol use, Colleen Corte, Ph.D., and Laura Szalacha, Ed.D., hypothesized in a poster presented at a joint meeting sponsored by the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Dr. Corte and Dr. Szalacha are with the health systems science department at the University of Illinois at Chicago.

A possible self is a person's conception of who he or she will be at a future time. Previous research has shown that possible selves play a strong role in risk behaviors. In turn, risk behaviors have been shown to reinforce and strengthen possible selves.

To test this hypothesis, the researchers recruited 79 children from schools and summer youth programs. The children were an average age of 10.7 years.

To assess the ability to conceive of a future self who drank alcohol (possible drinking self), the children were asked to rate how much the phrase “drink too much alcohol” is likely to describe them in the future. Lifetime drinking was assessed using a single question: Have you ever had more than a few sips of alcohol? Those who answered yes were asked about whether their parents knew.

Almost a fifth (19%) reported a drinking possible self; 19% also reported ever drinking, but 4% reported drinking when their parents were not aware of it. Forty percent of those with a drinking possible self reported ever drinking.

WASHINGTON – Children who can imagine drinking alcohol in the future may be at greater risk for early alcohol use, findings of a study of 79 children show.

The existence of a possible self who drinks alcohol might be an important predictor that mediates the effect of known precursors of alcohol problems–such as antisocial behavior and parental alcohol problems–on early alcohol use, Colleen Corte, Ph.D., and Laura Szalacha, Ed.D., hypothesized in a poster presented at a joint meeting sponsored by the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Dr. Corte and Dr. Szalacha are with the health systems science department at the University of Illinois at Chicago.

A possible self is a person's conception of who he or she will be at a future time. Previous research has shown that possible selves play a strong role in risk behaviors. In turn, risk behaviors have been shown to reinforce and strengthen possible selves.

To test this hypothesis, the researchers recruited 79 children from schools and summer youth programs. The children were an average age of 10.7 years.

To assess the ability to conceive of a future self who drank alcohol (possible drinking self), the children were asked to rate how much the phrase “drink too much alcohol” is likely to describe them in the future. Lifetime drinking was assessed using a single question: Have you ever had more than a few sips of alcohol? Those who answered yes were asked about whether their parents knew.

Almost a fifth (19%) reported a drinking possible self; 19% also reported ever drinking, but 4% reported drinking when their parents were not aware of it. Forty percent of those with a drinking possible self reported ever drinking.

WASHINGTON – Differences in response to alcohol suggest that African Americans may be at greater risk for alcoholism than whites, based on the preliminary results of an alcohol challenge study involving 160 participants.

“The surprising thing is that the response pattern for our sample is indicative of increased risk for African Americans,” Denis M. McCarthy, Ph.D., said in an interview.

Dr. McCarthy of the department of psychological sciences at the University of Missouri-Columbia and Sarah L. Pedersen, a graduate student, presented the study as a poster at a joint meeting sponsored by the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism.

African American subjects had increased stimulation and African American male subjects reported decreased sedation in response to an alcohol challenge, compared with the response seen in whites. The risk of developing alcohol problems is influenced in part by one's subjective response to alcohol. Studies have shown that individuals at risk for alcoholism report greater stimulation, less sedation, and/or a low response to alcohol, they said.

The findings are somewhat unexpected, given that previous research has clearly indicated a lower risk of alcoholism for African Americans, particularly in adolescence and young adulthood. African American youths tend to start drinking later and increase use slower than do white youths. African American youths also have higher rates of alcohol abstinence and engage in less heavy drinking in college.

The study involved 160 participants–48% of whom were male, with an average age of 22 years–who completed an alcohol challenge. Of these, 64% were African American. Participants were recruited through posted advertisements. At the first visit, participants completed clinical interviews and questionnaires. The alcohol challenge was conducted at the second visit.

For the alcohol challenge, baseline measurements were performed using the Biphasic Alcohol Effects Scale (BAES) and breath alcohol concentration (BrAC). The BAES is a self-reported rating scale designed to measure both stimulant and sedative effects of alcohol when blood alcohol content is increasing (ascending limb of the blood alcohol curve) and decreasing (descending limb). The BrAC allows the estimation of blood alcohol content.

Alcohol (vodka and tonic) was dosed by weight and gender–0.72 g/kg alcohol for men and 0.65 g/kg alcohol for women. This dosing was used to achieve an estimated peak blood alcohol concentration of 80 mg/dL (0.08%). Alcohol was consumed in 15 minutes and measurements were repeated at 15, 30, 45, 60, 90, 120, and 150 minutes after alcohol administration.

African Americans had sharper increases in stimulation from alcohol on the ascending limb of the blood alcohol curve, and white males had increased sedation. No differences were found between the races for stimulation or sedation on the descending limb, Dr. McCarthy and Ms. Pedersen wrote.

Stimulation on the ascending limb was related to drinking in the past month for African Americans but not for whites. Sedation on the ascending limb was related to drinking in the past month for both racial groups. Sedation on the descending limb was related to past-month drinking only for whites. African Americans reported lower levels of alcohol use during the past month, in terms of both frequency and quantity. African Americans also reported lower levels of alcohol risk factors: positive alcohol expectancies, disinhibited personality traits, and peer drinking.

“My initial thought is that the other protective factors found in African American college students are 'holding down' their drinking,” Dr. McCarthy said. “It will be important to see how these findings on response to alcohol fit in with other risk and protective factors.”

The researchers hope to look at differences in drinking culture between college-age African Americans and whites.

WASHINGTON – Differences in response to alcohol suggest that African Americans may be at greater risk for alcoholism than whites, based on the preliminary results of an alcohol challenge study involving 160 participants.

“The surprising thing is that the response pattern for our sample is indicative of increased risk for African Americans,” Denis M. McCarthy, Ph.D., said in an interview.

Dr. McCarthy of the department of psychological sciences at the University of Missouri-Columbia and Sarah L. Pedersen, a graduate student, presented the study as a poster at a joint meeting sponsored by the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism.

African American subjects had increased stimulation and African American male subjects reported decreased sedation in response to an alcohol challenge, compared with the response seen in whites. The risk of developing alcohol problems is influenced in part by one's subjective response to alcohol. Studies have shown that individuals at risk for alcoholism report greater stimulation, less sedation, and/or a low response to alcohol, they said.

The findings are somewhat unexpected, given that previous research has clearly indicated a lower risk of alcoholism for African Americans, particularly in adolescence and young adulthood. African American youths tend to start drinking later and increase use slower than do white youths. African American youths also have higher rates of alcohol abstinence and engage in less heavy drinking in college.

The study involved 160 participants–48% of whom were male, with an average age of 22 years–who completed an alcohol challenge. Of these, 64% were African American. Participants were recruited through posted advertisements. At the first visit, participants completed clinical interviews and questionnaires. The alcohol challenge was conducted at the second visit.

For the alcohol challenge, baseline measurements were performed using the Biphasic Alcohol Effects Scale (BAES) and breath alcohol concentration (BrAC). The BAES is a self-reported rating scale designed to measure both stimulant and sedative effects of alcohol when blood alcohol content is increasing (ascending limb of the blood alcohol curve) and decreasing (descending limb). The BrAC allows the estimation of blood alcohol content.

Alcohol (vodka and tonic) was dosed by weight and gender–0.72 g/kg alcohol for men and 0.65 g/kg alcohol for women. This dosing was used to achieve an estimated peak blood alcohol concentration of 80 mg/dL (0.08%). Alcohol was consumed in 15 minutes and measurements were repeated at 15, 30, 45, 60, 90, 120, and 150 minutes after alcohol administration.

African Americans had sharper increases in stimulation from alcohol on the ascending limb of the blood alcohol curve, and white males had increased sedation. No differences were found between the races for stimulation or sedation on the descending limb, Dr. McCarthy and Ms. Pedersen wrote.

Stimulation on the ascending limb was related to drinking in the past month for African Americans but not for whites. Sedation on the ascending limb was related to drinking in the past month for both racial groups. Sedation on the descending limb was related to past-month drinking only for whites. African Americans reported lower levels of alcohol use during the past month, in terms of both frequency and quantity. African Americans also reported lower levels of alcohol risk factors: positive alcohol expectancies, disinhibited personality traits, and peer drinking.

“My initial thought is that the other protective factors found in African American college students are 'holding down' their drinking,” Dr. McCarthy said. “It will be important to see how these findings on response to alcohol fit in with other risk and protective factors.”

The researchers hope to look at differences in drinking culture between college-age African Americans and whites.

WASHINGTON – Differences in response to alcohol suggest that African Americans may be at greater risk for alcoholism than whites, based on the preliminary results of an alcohol challenge study involving 160 participants.

“The surprising thing is that the response pattern for our sample is indicative of increased risk for African Americans,” Denis M. McCarthy, Ph.D., said in an interview.

Dr. McCarthy of the department of psychological sciences at the University of Missouri-Columbia and Sarah L. Pedersen, a graduate student, presented the study as a poster at a joint meeting sponsored by the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism.

African American subjects had increased stimulation and African American male subjects reported decreased sedation in response to an alcohol challenge, compared with the response seen in whites. The risk of developing alcohol problems is influenced in part by one's subjective response to alcohol. Studies have shown that individuals at risk for alcoholism report greater stimulation, less sedation, and/or a low response to alcohol, they said.

The findings are somewhat unexpected, given that previous research has clearly indicated a lower risk of alcoholism for African Americans, particularly in adolescence and young adulthood. African American youths tend to start drinking later and increase use slower than do white youths. African American youths also have higher rates of alcohol abstinence and engage in less heavy drinking in college.

The study involved 160 participants–48% of whom were male, with an average age of 22 years–who completed an alcohol challenge. Of these, 64% were African American. Participants were recruited through posted advertisements. At the first visit, participants completed clinical interviews and questionnaires. The alcohol challenge was conducted at the second visit.

For the alcohol challenge, baseline measurements were performed using the Biphasic Alcohol Effects Scale (BAES) and breath alcohol concentration (BrAC). The BAES is a self-reported rating scale designed to measure both stimulant and sedative effects of alcohol when blood alcohol content is increasing (ascending limb of the blood alcohol curve) and decreasing (descending limb). The BrAC allows the estimation of blood alcohol content.

Alcohol (vodka and tonic) was dosed by weight and gender–0.72 g/kg alcohol for men and 0.65 g/kg alcohol for women. This dosing was used to achieve an estimated peak blood alcohol concentration of 80 mg/dL (0.08%). Alcohol was consumed in 15 minutes and measurements were repeated at 15, 30, 45, 60, 90, 120, and 150 minutes after alcohol administration.

African Americans had sharper increases in stimulation from alcohol on the ascending limb of the blood alcohol curve, and white males had increased sedation. No differences were found between the races for stimulation or sedation on the descending limb, Dr. McCarthy and Ms. Pedersen wrote.

Stimulation on the ascending limb was related to drinking in the past month for African Americans but not for whites. Sedation on the ascending limb was related to drinking in the past month for both racial groups. Sedation on the descending limb was related to past-month drinking only for whites. African Americans reported lower levels of alcohol use during the past month, in terms of both frequency and quantity. African Americans also reported lower levels of alcohol risk factors: positive alcohol expectancies, disinhibited personality traits, and peer drinking.

“My initial thought is that the other protective factors found in African American college students are 'holding down' their drinking,” Dr. McCarthy said. “It will be important to see how these findings on response to alcohol fit in with other risk and protective factors.”

The researchers hope to look at differences in drinking culture between college-age African Americans and whites.

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.

PARIS — Treatment of atypical nevi with high-dose interferon alfa-2b may induce at least partial involution, based on the results of a small study.

Six of eight atypical nevi demonstrated a decrease in their greatest diameter, perimeter, or surface area, suggesting partial involution following treatment with high-dose interferon alfa-2b, reported Dr. Mona Amini-Adle of the department of dermatology at Hôpital de l'Hôtel Dieu, Lyon, France.

Partial clinical involution of atypical nevi was associated with an upregulation of CD4/CD8 ratio in the intra-nevi compartment, Dr. Amini-Adle said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, 10 patients with stage IIB-III melanoma, and at least four atypical nevi from each patient, were enrolled. The four nevi were identified as A-D at enrollment and photographed.

Two nevi were selected at random for removal prior to treatment; the remaining two were removed after 3 months of treatment. All nevi were evaluated clinically, pathologically, and with a double immunohistochemistry procedure (CD4-CD8; CD1a-CD83).

Patients were treated according to their melanoma status. Patients at high risk for melanoma were treated with a regimen of 20 million U/m

Dr. Amini-Adle reported on eight patients with a mean age of 36 years, half of whom were women. Sixteen clinical photos (eight pre- and eight posttreatment) from five patients were informative. Biopsy samples from eight patients were informative for 27 lesions—14 pre- and 13 posttreatment nevi. "We did not observe any histologic regression," said Dr. Amini-Adle.

Clinical atypia and histologic dysplasia were correlated in half of the lesions. The clinical changes were not accompanied by histologic signs of involution. Immunohistochemistry analysis showed alterations in lymphocyte infiltrates in nevi that were focal, with histologic signs of dysplasia and a significant upregulation of the CD4/CD8 ratio in the intra-nevi compartment (P = .0076).

No changes in lymphocyte response were observed after treatment, nor were any changes seen in the degree of atypia of these lesions. With regard to lymphocytic infiltrates, there was a trend of upregulation of CD4 cells and downregulation of CD8 cells, Dr. Amini-Adle said.

This resulted in upregulation of the CD4/CD8 ratio. These changes, however, were observed only in dysplastic nevi, not normal melanocytic nevi.

Dissociated responses of lymphocytes in both normal and atypical nevi suggest differential immunologic response to these entities. The dendritic cell infiltrate was not found to be influenced either in atypical nevi or normal nevi following treatment.

Atypical nevi have been shown to be nonobligate precursors of, and risk markers for, melanoma. Interferon alfa-2b is the only agent that has been shown to have a consistent and durable impact on relapse-free survival in melanoma patients, but it has not been studied for atypical nevi.

Interferon is known to enhance the immunogenicity of tumors. It is also known to suppress immune tolerance and to increase the degree of lymphocytic infiltrate in lesions that progress under treatment. Interestingly, in spontaneous regressive melanoma, the CD4/CD8 ratio is upregulated.

The meaning of upregulation in dysplastic nevi is unclear.

Dr. Amini-Adle noted that CD4 cells appear to play an important role in this regression.

PARIS — Treatment of atypical nevi with high-dose interferon alfa-2b may induce at least partial involution, based on the results of a small study.

Six of eight atypical nevi demonstrated a decrease in their greatest diameter, perimeter, or surface area, suggesting partial involution following treatment with high-dose interferon alfa-2b, reported Dr. Mona Amini-Adle of the department of dermatology at Hôpital de l'Hôtel Dieu, Lyon, France.

Partial clinical involution of atypical nevi was associated with an upregulation of CD4/CD8 ratio in the intra-nevi compartment, Dr. Amini-Adle said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, 10 patients with stage IIB-III melanoma, and at least four atypical nevi from each patient, were enrolled. The four nevi were identified as A-D at enrollment and photographed.

Two nevi were selected at random for removal prior to treatment; the remaining two were removed after 3 months of treatment. All nevi were evaluated clinically, pathologically, and with a double immunohistochemistry procedure (CD4-CD8; CD1a-CD83).

Patients were treated according to their melanoma status. Patients at high risk for melanoma were treated with a regimen of 20 million U/m

Dr. Amini-Adle reported on eight patients with a mean age of 36 years, half of whom were women. Sixteen clinical photos (eight pre- and eight posttreatment) from five patients were informative. Biopsy samples from eight patients were informative for 27 lesions—14 pre- and 13 posttreatment nevi. "We did not observe any histologic regression," said Dr. Amini-Adle.

Clinical atypia and histologic dysplasia were correlated in half of the lesions. The clinical changes were not accompanied by histologic signs of involution. Immunohistochemistry analysis showed alterations in lymphocyte infiltrates in nevi that were focal, with histologic signs of dysplasia and a significant upregulation of the CD4/CD8 ratio in the intra-nevi compartment (P = .0076).

No changes in lymphocyte response were observed after treatment, nor were any changes seen in the degree of atypia of these lesions. With regard to lymphocytic infiltrates, there was a trend of upregulation of CD4 cells and downregulation of CD8 cells, Dr. Amini-Adle said.

This resulted in upregulation of the CD4/CD8 ratio. These changes, however, were observed only in dysplastic nevi, not normal melanocytic nevi.

Dissociated responses of lymphocytes in both normal and atypical nevi suggest differential immunologic response to these entities. The dendritic cell infiltrate was not found to be influenced either in atypical nevi or normal nevi following treatment.

Atypical nevi have been shown to be nonobligate precursors of, and risk markers for, melanoma. Interferon alfa-2b is the only agent that has been shown to have a consistent and durable impact on relapse-free survival in melanoma patients, but it has not been studied for atypical nevi.

Interferon is known to enhance the immunogenicity of tumors. It is also known to suppress immune tolerance and to increase the degree of lymphocytic infiltrate in lesions that progress under treatment. Interestingly, in spontaneous regressive melanoma, the CD4/CD8 ratio is upregulated.

The meaning of upregulation in dysplastic nevi is unclear.

Dr. Amini-Adle noted that CD4 cells appear to play an important role in this regression.

PARIS — Treatment of atypical nevi with high-dose interferon alfa-2b may induce at least partial involution, based on the results of a small study.

Six of eight atypical nevi demonstrated a decrease in their greatest diameter, perimeter, or surface area, suggesting partial involution following treatment with high-dose interferon alfa-2b, reported Dr. Mona Amini-Adle of the department of dermatology at Hôpital de l'Hôtel Dieu, Lyon, France.

Partial clinical involution of atypical nevi was associated with an upregulation of CD4/CD8 ratio in the intra-nevi compartment, Dr. Amini-Adle said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, 10 patients with stage IIB-III melanoma, and at least four atypical nevi from each patient, were enrolled. The four nevi were identified as A-D at enrollment and photographed.

Two nevi were selected at random for removal prior to treatment; the remaining two were removed after 3 months of treatment. All nevi were evaluated clinically, pathologically, and with a double immunohistochemistry procedure (CD4-CD8; CD1a-CD83).

Patients were treated according to their melanoma status. Patients at high risk for melanoma were treated with a regimen of 20 million U/m

Dr. Amini-Adle reported on eight patients with a mean age of 36 years, half of whom were women. Sixteen clinical photos (eight pre- and eight posttreatment) from five patients were informative. Biopsy samples from eight patients were informative for 27 lesions—14 pre- and 13 posttreatment nevi. "We did not observe any histologic regression," said Dr. Amini-Adle.

Clinical atypia and histologic dysplasia were correlated in half of the lesions. The clinical changes were not accompanied by histologic signs of involution. Immunohistochemistry analysis showed alterations in lymphocyte infiltrates in nevi that were focal, with histologic signs of dysplasia and a significant upregulation of the CD4/CD8 ratio in the intra-nevi compartment (P = .0076).

No changes in lymphocyte response were observed after treatment, nor were any changes seen in the degree of atypia of these lesions. With regard to lymphocytic infiltrates, there was a trend of upregulation of CD4 cells and downregulation of CD8 cells, Dr. Amini-Adle said.

This resulted in upregulation of the CD4/CD8 ratio. These changes, however, were observed only in dysplastic nevi, not normal melanocytic nevi.

Dissociated responses of lymphocytes in both normal and atypical nevi suggest differential immunologic response to these entities. The dendritic cell infiltrate was not found to be influenced either in atypical nevi or normal nevi following treatment.

Atypical nevi have been shown to be nonobligate precursors of, and risk markers for, melanoma. Interferon alfa-2b is the only agent that has been shown to have a consistent and durable impact on relapse-free survival in melanoma patients, but it has not been studied for atypical nevi.

Interferon is known to enhance the immunogenicity of tumors. It is also known to suppress immune tolerance and to increase the degree of lymphocytic infiltrate in lesions that progress under treatment. Interestingly, in spontaneous regressive melanoma, the CD4/CD8 ratio is upregulated.

The meaning of upregulation in dysplastic nevi is unclear.

Dr. Amini-Adle noted that CD4 cells appear to play an important role in this regression.

PARIS — Surgical excision is more effective than photodynamic therapy for the treatment of nodular basal cell carcinoma, based on the results of a study of more than 100 patients.

The cumulative incidence of failure was 2% for surgical excision, compared with 30% for photodynamic therapy at a 3-year interim analysis.

In all, 171 primary basal cell carcinomas in 149 patients were treated—88 in the surgical excision group and 83 in the phototherapy group. At 3-month follow-up, there were five basal cell carcinoma treatment failures in the phototherapy group (6%) and two (2.3%) in the surgical excision group.

"There's actually a higher risk of incomplete treatment after treatment with photodynamic therapy for primary basal cell carcinomas," Dr. Klara Mosterd of the department of dermatology at the University Hospital Maastricht (the Netherlands), said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, primary basal cell carcinomas with a maximum size of 2 cm were randomly assigned to either photodynamic therapy or surgical excision. Exclusion criteria included tumors with mixed histology, recurrent basal cell carcinoma, three or more tumors per patient, and short life expectancy, among others.

Tumors treated with photodynamic therapy first underwent surgical debulking 2 weeks prior to treatment. Illumination was performed 4 hours after application of 5-aminolevulinic acid (ALA) cream. Tumors that were illuminated were illuminated again an hour later (from 585 nm to 720 nm, 75 J/cm

Surgical excision was performed under local anesthesia, using a 3-mm margin. Histologic examination then was performed. Any residual tumor found on follow-up was excised again, Dr. Mosterd said at the meeting.

After the first follow-up visit at 3 months, all patients were seen every 6 months up to 2 years and then once yearly up to 5 years.

Although surgical excision is the treatment of choice in patients with nodular basal cell carcinoma, photodynamic therapy has been shown to be an effective treatment for superficial basal cell carcinoma. This prompted the researchers to explore the effectiveness of photodynamic therapy on nodular basal cell carcinoma.

PARIS — Surgical excision is more effective than photodynamic therapy for the treatment of nodular basal cell carcinoma, based on the results of a study of more than 100 patients.

The cumulative incidence of failure was 2% for surgical excision, compared with 30% for photodynamic therapy at a 3-year interim analysis.

In all, 171 primary basal cell carcinomas in 149 patients were treated—88 in the surgical excision group and 83 in the phototherapy group. At 3-month follow-up, there were five basal cell carcinoma treatment failures in the phototherapy group (6%) and two (2.3%) in the surgical excision group.

"There's actually a higher risk of incomplete treatment after treatment with photodynamic therapy for primary basal cell carcinomas," Dr. Klara Mosterd of the department of dermatology at the University Hospital Maastricht (the Netherlands), said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, primary basal cell carcinomas with a maximum size of 2 cm were randomly assigned to either photodynamic therapy or surgical excision. Exclusion criteria included tumors with mixed histology, recurrent basal cell carcinoma, three or more tumors per patient, and short life expectancy, among others.

Tumors treated with photodynamic therapy first underwent surgical debulking 2 weeks prior to treatment. Illumination was performed 4 hours after application of 5-aminolevulinic acid (ALA) cream. Tumors that were illuminated were illuminated again an hour later (from 585 nm to 720 nm, 75 J/cm

Surgical excision was performed under local anesthesia, using a 3-mm margin. Histologic examination then was performed. Any residual tumor found on follow-up was excised again, Dr. Mosterd said at the meeting.

After the first follow-up visit at 3 months, all patients were seen every 6 months up to 2 years and then once yearly up to 5 years.

Although surgical excision is the treatment of choice in patients with nodular basal cell carcinoma, photodynamic therapy has been shown to be an effective treatment for superficial basal cell carcinoma. This prompted the researchers to explore the effectiveness of photodynamic therapy on nodular basal cell carcinoma.

PARIS — Surgical excision is more effective than photodynamic therapy for the treatment of nodular basal cell carcinoma, based on the results of a study of more than 100 patients.

The cumulative incidence of failure was 2% for surgical excision, compared with 30% for photodynamic therapy at a 3-year interim analysis.

In all, 171 primary basal cell carcinomas in 149 patients were treated—88 in the surgical excision group and 83 in the phototherapy group. At 3-month follow-up, there were five basal cell carcinoma treatment failures in the phototherapy group (6%) and two (2.3%) in the surgical excision group.

"There's actually a higher risk of incomplete treatment after treatment with photodynamic therapy for primary basal cell carcinomas," Dr. Klara Mosterd of the department of dermatology at the University Hospital Maastricht (the Netherlands), said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, primary basal cell carcinomas with a maximum size of 2 cm were randomly assigned to either photodynamic therapy or surgical excision. Exclusion criteria included tumors with mixed histology, recurrent basal cell carcinoma, three or more tumors per patient, and short life expectancy, among others.

Tumors treated with photodynamic therapy first underwent surgical debulking 2 weeks prior to treatment. Illumination was performed 4 hours after application of 5-aminolevulinic acid (ALA) cream. Tumors that were illuminated were illuminated again an hour later (from 585 nm to 720 nm, 75 J/cm

Surgical excision was performed under local anesthesia, using a 3-mm margin. Histologic examination then was performed. Any residual tumor found on follow-up was excised again, Dr. Mosterd said at the meeting.

After the first follow-up visit at 3 months, all patients were seen every 6 months up to 2 years and then once yearly up to 5 years.

Although surgical excision is the treatment of choice in patients with nodular basal cell carcinoma, photodynamic therapy has been shown to be an effective treatment for superficial basal cell carcinoma. This prompted the researchers to explore the effectiveness of photodynamic therapy on nodular basal cell carcinoma.

PARIS — Not only are patients with cutaneous T-cell lymphoma more likely to be colonized with Staphylococcus aureus, compared with healthy individuals, but S. aureus colonization appears to be directly related to the body surface area involvement, according to a study of 100 adults.

Researchers at Northwestern University, Chicago, compared colonization rates for 50 CTCL patients, 25 patients with psoriasis, and 25 healthy controls enrolled from a single dermatology clinic. S. aureus colonization was found in 44% of CTCL patients, 48% of psoriasis patients, and 28% of healthy controls.

Colonization with S. aureus was significantly associated with increased body surface area involvement of CTCL, Dr. Victoria Nguyen reported at the annual congress of the European Academy of Dermatology and Venereology.

Healthy controls were seen for routine skin examination. Patients with CTCL and psoriasis had to have active lesions in order to be included in the study.

The control participants were matched with case patients by age, sex, and anatomical skin site.

Potential participants were excluded if they had active infections, had taken antibiotics in the previous 3 months, or had undergone decolonization in the last 6 months. Patients who had HIV infection, were on chemotherapy, or were otherwise immunocompromised were also excluded.

Culture swabs were obtained from nares and lesional skin or normal skin in the healthy control group. Body surface examination was performed on CTCL patients.

Of the patients found to have S. aureus colonization, the majority was community associated (68%, 83%, and 71% for the CTCL, psoriasis, and control groups, respectively). The rate of methicillin-resistant S. aureus colonization was 2% in the CTCL group, 12% in the psoriasis group, and 8% in the healthy control group.

"Our study is likely an underestimation of S. aureus colonization, given that our excluded population [of CTCL patients] did have a greater rate of S. aureus colonization, up to 80%," noted Dr. Nguyen.

Infection is a common complication of CTCL, with S. aureus being the most common pathogen behind these infections, said Dr. Nguyen, who is a dermatology resident at Northwestern.

The reason for this predisposition to infection among CTCL patients may be threefold. First, these patients have an impaired skin barrier. They also have a decreased repertoire of normal circulating T cells. Lastly, these patients may also be immunosuppressed.

"CTCL is a Th-2-mediated pathway. So, similar to atopic dermatitis, there's perhaps a decrease in antimicrobial peptides in these patients, predisposing them to Staphylococcus aureus colonization," she said.

"The reason for the similarity in the colonization rates among the CTCL and psoriasis groups may be because these patients have an impaired skin barrier; both groups may have more frequent visits to the clinic; and hospitalizations and procedures may be higher in these groups," she added.

Prior studies have shown in vitro stimulation of CTCL cell lines with staphylococcal toxins, positive S. aureus cultures in half of Sézary syndrome patients, and the improvement of Sézary syndrome with antibiotic use.

"It may be that perhaps treating the colonization and infection in CTCL patients may improve severity," said Dr. Nguyen.

At Northwestern, she and her colleagues have treated S. aureus colonization in CTCL patients with resulting improvements in severity.

"We do recommend for our patients, who look like they've got crusting or excoriation, that they get sodium hypochlorite baths—a quarter cup of 6% sodium hypochlorite in a bath tub—daily or weekly to decrease colonization," she concluded.

PARIS — Not only are patients with cutaneous T-cell lymphoma more likely to be colonized with Staphylococcus aureus, compared with healthy individuals, but S. aureus colonization appears to be directly related to the body surface area involvement, according to a study of 100 adults.

Researchers at Northwestern University, Chicago, compared colonization rates for 50 CTCL patients, 25 patients with psoriasis, and 25 healthy controls enrolled from a single dermatology clinic. S. aureus colonization was found in 44% of CTCL patients, 48% of psoriasis patients, and 28% of healthy controls.

Colonization with S. aureus was significantly associated with increased body surface area involvement of CTCL, Dr. Victoria Nguyen reported at the annual congress of the European Academy of Dermatology and Venereology.

Healthy controls were seen for routine skin examination. Patients with CTCL and psoriasis had to have active lesions in order to be included in the study.

The control participants were matched with case patients by age, sex, and anatomical skin site.

Potential participants were excluded if they had active infections, had taken antibiotics in the previous 3 months, or had undergone decolonization in the last 6 months. Patients who had HIV infection, were on chemotherapy, or were otherwise immunocompromised were also excluded.

Culture swabs were obtained from nares and lesional skin or normal skin in the healthy control group. Body surface examination was performed on CTCL patients.

Of the patients found to have S. aureus colonization, the majority was community associated (68%, 83%, and 71% for the CTCL, psoriasis, and control groups, respectively). The rate of methicillin-resistant S. aureus colonization was 2% in the CTCL group, 12% in the psoriasis group, and 8% in the healthy control group.

"Our study is likely an underestimation of S. aureus colonization, given that our excluded population [of CTCL patients] did have a greater rate of S. aureus colonization, up to 80%," noted Dr. Nguyen.

Infection is a common complication of CTCL, with S. aureus being the most common pathogen behind these infections, said Dr. Nguyen, who is a dermatology resident at Northwestern.

The reason for this predisposition to infection among CTCL patients may be threefold. First, these patients have an impaired skin barrier. They also have a decreased repertoire of normal circulating T cells. Lastly, these patients may also be immunosuppressed.

"CTCL is a Th-2-mediated pathway. So, similar to atopic dermatitis, there's perhaps a decrease in antimicrobial peptides in these patients, predisposing them to Staphylococcus aureus colonization," she said.

"The reason for the similarity in the colonization rates among the CTCL and psoriasis groups may be because these patients have an impaired skin barrier; both groups may have more frequent visits to the clinic; and hospitalizations and procedures may be higher in these groups," she added.

Prior studies have shown in vitro stimulation of CTCL cell lines with staphylococcal toxins, positive S. aureus cultures in half of Sézary syndrome patients, and the improvement of Sézary syndrome with antibiotic use.

"It may be that perhaps treating the colonization and infection in CTCL patients may improve severity," said Dr. Nguyen.

At Northwestern, she and her colleagues have treated S. aureus colonization in CTCL patients with resulting improvements in severity.

"We do recommend for our patients, who look like they've got crusting or excoriation, that they get sodium hypochlorite baths—a quarter cup of 6% sodium hypochlorite in a bath tub—daily or weekly to decrease colonization," she concluded.

PARIS — Not only are patients with cutaneous T-cell lymphoma more likely to be colonized with Staphylococcus aureus, compared with healthy individuals, but S. aureus colonization appears to be directly related to the body surface area involvement, according to a study of 100 adults.

Researchers at Northwestern University, Chicago, compared colonization rates for 50 CTCL patients, 25 patients with psoriasis, and 25 healthy controls enrolled from a single dermatology clinic. S. aureus colonization was found in 44% of CTCL patients, 48% of psoriasis patients, and 28% of healthy controls.

Colonization with S. aureus was significantly associated with increased body surface area involvement of CTCL, Dr. Victoria Nguyen reported at the annual congress of the European Academy of Dermatology and Venereology.

Healthy controls were seen for routine skin examination. Patients with CTCL and psoriasis had to have active lesions in order to be included in the study.

The control participants were matched with case patients by age, sex, and anatomical skin site.

Potential participants were excluded if they had active infections, had taken antibiotics in the previous 3 months, or had undergone decolonization in the last 6 months. Patients who had HIV infection, were on chemotherapy, or were otherwise immunocompromised were also excluded.

Culture swabs were obtained from nares and lesional skin or normal skin in the healthy control group. Body surface examination was performed on CTCL patients.

Of the patients found to have S. aureus colonization, the majority was community associated (68%, 83%, and 71% for the CTCL, psoriasis, and control groups, respectively). The rate of methicillin-resistant S. aureus colonization was 2% in the CTCL group, 12% in the psoriasis group, and 8% in the healthy control group.

"Our study is likely an underestimation of S. aureus colonization, given that our excluded population [of CTCL patients] did have a greater rate of S. aureus colonization, up to 80%," noted Dr. Nguyen.

Infection is a common complication of CTCL, with S. aureus being the most common pathogen behind these infections, said Dr. Nguyen, who is a dermatology resident at Northwestern.

The reason for this predisposition to infection among CTCL patients may be threefold. First, these patients have an impaired skin barrier. They also have a decreased repertoire of normal circulating T cells. Lastly, these patients may also be immunosuppressed.

"CTCL is a Th-2-mediated pathway. So, similar to atopic dermatitis, there's perhaps a decrease in antimicrobial peptides in these patients, predisposing them to Staphylococcus aureus colonization," she said.

"The reason for the similarity in the colonization rates among the CTCL and psoriasis groups may be because these patients have an impaired skin barrier; both groups may have more frequent visits to the clinic; and hospitalizations and procedures may be higher in these groups," she added.

Prior studies have shown in vitro stimulation of CTCL cell lines with staphylococcal toxins, positive S. aureus cultures in half of Sézary syndrome patients, and the improvement of Sézary syndrome with antibiotic use.

"It may be that perhaps treating the colonization and infection in CTCL patients may improve severity," said Dr. Nguyen.

At Northwestern, she and her colleagues have treated S. aureus colonization in CTCL patients with resulting improvements in severity.

"We do recommend for our patients, who look like they've got crusting or excoriation, that they get sodium hypochlorite baths—a quarter cup of 6% sodium hypochlorite in a bath tub—daily or weekly to decrease colonization," she concluded.