Jeff Evans

WASHINGTON – Gabapentin brought greater relief of symptoms to patients with primary fibromyalgia than placebo in a randomized, double-blind trial, Dr. Lesley M. Arnold reported at the annual meeting of the American College of Rheumatology.

Gabapentin is known to be effective for neuropathic pain conditions, and growing evidence suggests fibromyalgia might share some of the same pathogenic mechanisms, said Dr. Arnold of the department of psychiatry at the University of Cincinnati.

The trial of 150 patients involved a 60-day phase when other psychotropic, sleep, and pain medications (besides over-the-counter NSAIDs and acetaminophen) were not allowed, a 6-week acute therapy phase when the dosage was titrated to 1,200–2,400 mg/day, and a 6-week stable dosage phase.

At week 12, the 75 gabapentin-treated patients had a significantly greater mean improvement on the Brief Pain Inventory (BPI) 24-hour average pain severity score than did the 75 placebo patients; this was the primary outcome of the study. Gabapentin-treated patients scored an average of 0.92 less on that inventory than did placebo patients. The BPI 24-hour average pain severity score is measured on a range from 0 (no pain) to 10 (worst pain imaginable).

A significantly higher percentage of gabapentin patients responded to treatment than did placebo patients (51% vs. 31%).

Gabapentin also significantly improved measures of the interference and impact of symptoms on daily life and functioning, clinical impressions, and sleep. But the drug provided no significant changes in tender point threshold or relief of depressive symptoms, said Dr. Arnold, who disclosed that she has received research grants and consulting fees or other payments from Pfizer Inc., and has served on its speakers' bureau.

The trial was supported by the National Institutes of Health.

WASHINGTON – Gabapentin brought greater relief of symptoms to patients with primary fibromyalgia than placebo in a randomized, double-blind trial, Dr. Lesley M. Arnold reported at the annual meeting of the American College of Rheumatology.

Gabapentin is known to be effective for neuropathic pain conditions, and growing evidence suggests fibromyalgia might share some of the same pathogenic mechanisms, said Dr. Arnold of the department of psychiatry at the University of Cincinnati.

The trial of 150 patients involved a 60-day phase when other psychotropic, sleep, and pain medications (besides over-the-counter NSAIDs and acetaminophen) were not allowed, a 6-week acute therapy phase when the dosage was titrated to 1,200–2,400 mg/day, and a 6-week stable dosage phase.

At week 12, the 75 gabapentin-treated patients had a significantly greater mean improvement on the Brief Pain Inventory (BPI) 24-hour average pain severity score than did the 75 placebo patients; this was the primary outcome of the study. Gabapentin-treated patients scored an average of 0.92 less on that inventory than did placebo patients. The BPI 24-hour average pain severity score is measured on a range from 0 (no pain) to 10 (worst pain imaginable).

A significantly higher percentage of gabapentin patients responded to treatment than did placebo patients (51% vs. 31%).

Gabapentin also significantly improved measures of the interference and impact of symptoms on daily life and functioning, clinical impressions, and sleep. But the drug provided no significant changes in tender point threshold or relief of depressive symptoms, said Dr. Arnold, who disclosed that she has received research grants and consulting fees or other payments from Pfizer Inc., and has served on its speakers' bureau.

The trial was supported by the National Institutes of Health.

WASHINGTON – Gabapentin brought greater relief of symptoms to patients with primary fibromyalgia than placebo in a randomized, double-blind trial, Dr. Lesley M. Arnold reported at the annual meeting of the American College of Rheumatology.

Gabapentin is known to be effective for neuropathic pain conditions, and growing evidence suggests fibromyalgia might share some of the same pathogenic mechanisms, said Dr. Arnold of the department of psychiatry at the University of Cincinnati.

The trial of 150 patients involved a 60-day phase when other psychotropic, sleep, and pain medications (besides over-the-counter NSAIDs and acetaminophen) were not allowed, a 6-week acute therapy phase when the dosage was titrated to 1,200–2,400 mg/day, and a 6-week stable dosage phase.

At week 12, the 75 gabapentin-treated patients had a significantly greater mean improvement on the Brief Pain Inventory (BPI) 24-hour average pain severity score than did the 75 placebo patients; this was the primary outcome of the study. Gabapentin-treated patients scored an average of 0.92 less on that inventory than did placebo patients. The BPI 24-hour average pain severity score is measured on a range from 0 (no pain) to 10 (worst pain imaginable).

A significantly higher percentage of gabapentin patients responded to treatment than did placebo patients (51% vs. 31%).

Gabapentin also significantly improved measures of the interference and impact of symptoms on daily life and functioning, clinical impressions, and sleep. But the drug provided no significant changes in tender point threshold or relief of depressive symptoms, said Dr. Arnold, who disclosed that she has received research grants and consulting fees or other payments from Pfizer Inc., and has served on its speakers' bureau.

The trial was supported by the National Institutes of Health.

WASHINGTON – An association between a motor vehicle collision and the development of widespread body pain in some individuals was not supported by findings from an ongoing prospective study comparing two different cohorts.

However, the study of more than 8,000 people did suggest that such collisions may be associated with a post-crash onset of axial skeleton pain, John McBeth, Ph.D., reported at the annual meeting of the American College of Rheumatology.

“Physical stressors have been implicated in the onset of widespread pain disorders; particularly, whiplash experienced during a motor vehicle collision has been associated with the etiology of fibromyalgia,” said Dr. McBeth, senior lecturer in rheumatic disease epidemiology at the University of Manchester (England).

In the current study, a cohort of 1,499 patients aged 17–70 years who were involved in a motor vehicle collision (MVC) were compared with a control cohort of 6,792 individuals aged 25–65 years who participated in a pain survey.

Among patients who did not have widespread pain at baseline, 641 of 951 MVC patients and 3,058 of 3,780 control subjects participated in a 15-month follow-up. The rate of new-onset widespread pain in these subjects was similar between the MVC (8.4%) and control groups (11.6%). There also was no relationship between the severity of the collision and the development of widespread pain. These comparisons were adjusted for age, gender, pain at baseline, and psychological status. “This surprised us because we expected to see some kind of relationship between crash severity and the onset of widespread pain,” he said.

New-onset axial skeleton pain occurred at similar rates in the MVC (20%) and control cohorts (21%). But patients who had a severe collision were significantly more likely to report new-onset axial skeleton pain at the 15-month follow-up than were control patients.

This relationship persisted after adjustment for pain and psychological status at baseline.

The patients who developed axial skeleton pain may be “on the path” to developing widespread pain. With longer follow-up, the rate of new-onset widespread pain may be higher, Dr. McBeth said.

Previous studies have found that physical and psychosocial stressors are associated with an increased risk of new-onset widespread pain.

In one study of people who were in MVCs, the rate of new-onset fibromyalgia after the accident was significantly greater among those patients who had a cervical spine injury than it was in those patients who had leg fractures (Arthritis Rheum. 1997;40:446–52).

A case-control study found about 40% of fibromyalgia patients could recall a stressful event that may have precipitated the onset of their symptoms; these patients were most likely to report that a fracture, surgery, or workplace injury preceded the symptoms. Fibromyalgia patients were not more likely than controls to recall an MVC as a precipitating factor (Rheumatology [Oxford] 2002;41:450–3).

But an abstract presented at the annual meeting of the ACR in 2004 reported that among patients who had presented to an emergency department, the rate of new-onset fibromyalgia was significantly higher in those who had been in an MVC than in a control group of patients who had had a minor laceration. The MVC patients who reported neck pain at the time of presentation had the highest risk for developing fibromyalgia.

However, those studies did not take the role of psychological factors into account in relation to the onset of widespread body pain, Dr. McBeth said.

When he and his colleagues conducted a population-based, prospective study of 1,658 adults who did not have widespread pain at baseline, they found that individuals who reported high levels of somatic symptoms, illness behavior, psychological distress, and fatigue at baseline had a significantly increased risk of developing chronic widespread pain after 1 year (Arthritis Rheum. 2001;44:940–6).

WASHINGTON – An association between a motor vehicle collision and the development of widespread body pain in some individuals was not supported by findings from an ongoing prospective study comparing two different cohorts.

However, the study of more than 8,000 people did suggest that such collisions may be associated with a post-crash onset of axial skeleton pain, John McBeth, Ph.D., reported at the annual meeting of the American College of Rheumatology.

“Physical stressors have been implicated in the onset of widespread pain disorders; particularly, whiplash experienced during a motor vehicle collision has been associated with the etiology of fibromyalgia,” said Dr. McBeth, senior lecturer in rheumatic disease epidemiology at the University of Manchester (England).

In the current study, a cohort of 1,499 patients aged 17–70 years who were involved in a motor vehicle collision (MVC) were compared with a control cohort of 6,792 individuals aged 25–65 years who participated in a pain survey.

Among patients who did not have widespread pain at baseline, 641 of 951 MVC patients and 3,058 of 3,780 control subjects participated in a 15-month follow-up. The rate of new-onset widespread pain in these subjects was similar between the MVC (8.4%) and control groups (11.6%). There also was no relationship between the severity of the collision and the development of widespread pain. These comparisons were adjusted for age, gender, pain at baseline, and psychological status. “This surprised us because we expected to see some kind of relationship between crash severity and the onset of widespread pain,” he said.

New-onset axial skeleton pain occurred at similar rates in the MVC (20%) and control cohorts (21%). But patients who had a severe collision were significantly more likely to report new-onset axial skeleton pain at the 15-month follow-up than were control patients.

This relationship persisted after adjustment for pain and psychological status at baseline.

The patients who developed axial skeleton pain may be “on the path” to developing widespread pain. With longer follow-up, the rate of new-onset widespread pain may be higher, Dr. McBeth said.

Previous studies have found that physical and psychosocial stressors are associated with an increased risk of new-onset widespread pain.

In one study of people who were in MVCs, the rate of new-onset fibromyalgia after the accident was significantly greater among those patients who had a cervical spine injury than it was in those patients who had leg fractures (Arthritis Rheum. 1997;40:446–52).

A case-control study found about 40% of fibromyalgia patients could recall a stressful event that may have precipitated the onset of their symptoms; these patients were most likely to report that a fracture, surgery, or workplace injury preceded the symptoms. Fibromyalgia patients were not more likely than controls to recall an MVC as a precipitating factor (Rheumatology [Oxford] 2002;41:450–3).

But an abstract presented at the annual meeting of the ACR in 2004 reported that among patients who had presented to an emergency department, the rate of new-onset fibromyalgia was significantly higher in those who had been in an MVC than in a control group of patients who had had a minor laceration. The MVC patients who reported neck pain at the time of presentation had the highest risk for developing fibromyalgia.

However, those studies did not take the role of psychological factors into account in relation to the onset of widespread body pain, Dr. McBeth said.

When he and his colleagues conducted a population-based, prospective study of 1,658 adults who did not have widespread pain at baseline, they found that individuals who reported high levels of somatic symptoms, illness behavior, psychological distress, and fatigue at baseline had a significantly increased risk of developing chronic widespread pain after 1 year (Arthritis Rheum. 2001;44:940–6).

WASHINGTON – An association between a motor vehicle collision and the development of widespread body pain in some individuals was not supported by findings from an ongoing prospective study comparing two different cohorts.

However, the study of more than 8,000 people did suggest that such collisions may be associated with a post-crash onset of axial skeleton pain, John McBeth, Ph.D., reported at the annual meeting of the American College of Rheumatology.

“Physical stressors have been implicated in the onset of widespread pain disorders; particularly, whiplash experienced during a motor vehicle collision has been associated with the etiology of fibromyalgia,” said Dr. McBeth, senior lecturer in rheumatic disease epidemiology at the University of Manchester (England).

In the current study, a cohort of 1,499 patients aged 17–70 years who were involved in a motor vehicle collision (MVC) were compared with a control cohort of 6,792 individuals aged 25–65 years who participated in a pain survey.

Among patients who did not have widespread pain at baseline, 641 of 951 MVC patients and 3,058 of 3,780 control subjects participated in a 15-month follow-up. The rate of new-onset widespread pain in these subjects was similar between the MVC (8.4%) and control groups (11.6%). There also was no relationship between the severity of the collision and the development of widespread pain. These comparisons were adjusted for age, gender, pain at baseline, and psychological status. “This surprised us because we expected to see some kind of relationship between crash severity and the onset of widespread pain,” he said.

New-onset axial skeleton pain occurred at similar rates in the MVC (20%) and control cohorts (21%). But patients who had a severe collision were significantly more likely to report new-onset axial skeleton pain at the 15-month follow-up than were control patients.

This relationship persisted after adjustment for pain and psychological status at baseline.

The patients who developed axial skeleton pain may be “on the path” to developing widespread pain. With longer follow-up, the rate of new-onset widespread pain may be higher, Dr. McBeth said.

Previous studies have found that physical and psychosocial stressors are associated with an increased risk of new-onset widespread pain.

In one study of people who were in MVCs, the rate of new-onset fibromyalgia after the accident was significantly greater among those patients who had a cervical spine injury than it was in those patients who had leg fractures (Arthritis Rheum. 1997;40:446–52).

A case-control study found about 40% of fibromyalgia patients could recall a stressful event that may have precipitated the onset of their symptoms; these patients were most likely to report that a fracture, surgery, or workplace injury preceded the symptoms. Fibromyalgia patients were not more likely than controls to recall an MVC as a precipitating factor (Rheumatology [Oxford] 2002;41:450–3).

But an abstract presented at the annual meeting of the ACR in 2004 reported that among patients who had presented to an emergency department, the rate of new-onset fibromyalgia was significantly higher in those who had been in an MVC than in a control group of patients who had had a minor laceration. The MVC patients who reported neck pain at the time of presentation had the highest risk for developing fibromyalgia.

However, those studies did not take the role of psychological factors into account in relation to the onset of widespread body pain, Dr. McBeth said.

When he and his colleagues conducted a population-based, prospective study of 1,658 adults who did not have widespread pain at baseline, they found that individuals who reported high levels of somatic symptoms, illness behavior, psychological distress, and fatigue at baseline had a significantly increased risk of developing chronic widespread pain after 1 year (Arthritis Rheum. 2001;44:940–6).

VAIL, COLO. — The superficial injection of many botulinum toxin type A microdroplets may create a more natural-looking brow lift than more aggressive treatment of the central frontalis and nearby depressor muscles, Dr. Kenneth D. Steinsapir said at a symposium sponsored by the American Academy of Facial Plastic and Reconstructive Surgery.

In the area where Dr. Steinsapir practices, a common technique for raising the brow includes botulinum toxin type A (Botox) injections to the central forehead (leaving the lateral frontalis alone), aggressive treatment of the corrugator and procerus muscles, and "pretty aggressive treatment" in the crow's feet area, he said.

This technique creates a central depression and smoothing of the forehead and significant, unopposed elevation of the frontalis, which produces a taut, arching central brow. Extreme versions of this have been given the moniker "Klingon forehead," said Dr. Steinsapir, a cosmetic, eye, and facial plastic surgeon in private practice in Los Angeles.

These patients have smoother horizontal forehead lines, but often at the expense of brow position depression in which the eyebrows crowd into the eyes.

"We have these treatment patterns because we're concerned that we'll get a ptosis after Botox treatment," he noted.

"Aesthetically, I think we can all agree that there is something not optimal about these faces," which are often seen in actresses, Dr. Steinsapir said. "This type of fakeness creates an impression in the public that Botox is a paralytic and undesirable at best."

"The key is, I think, to have a clearer picture of the anatomy and how these muscles interact," he continued.

"Brow position is really determined by the antagonists—the frontalis is really the only elevator in the brow. A substantial portion of the other muscles are brow depressors—the corrugators, the procerus, and the depressor supercilii," he said at the symposium, which was also sponsored by the American Society for Dermatologic Surgery and the American Society of Ophthalmic Plastic and Reconstructive Surgery.

To lessen the pronounced brow arch that occurs with that technique, Dr. Steinsapir developed his microdroplet technique, in which he aggressively treats the frontalis at and below the brow by injecting "smaller and smaller volumes of fluid in multiple locations." These microdroplets have volumes of 10–50 mcL of injectable saline; he has worked with microdroplets that contain 0.001–1 U Botox.

Dr. Steinsapir's currently preferred starting treatment is based on 100 U Botox and 3 mL of injectable saline, which equals about 0.33 U of Botox per 10 mcL.

He uses 32- and 33-gauge needles, which are more comfortable for the patient than a 30-gauge needle. He also uses magnification and subsurface illumination to see the subsurface vasculature "a little bit better," although he has not performed a study to determine if it reduces the rate of bruising, he said.

A typical treatment involves a total of about 100 microdroplets placed in double or triple rows just above, in, and below the brow, stopping around the level of the lowest brow cilia. The microdroplet injections are placed superficially about 1 mm into the skin to trap the Botox at the interface between the orbicularis oculi and the skin. For crow's feet, he will usually stop just before the midline of the lateral palpebral raphe. The glabellar area is also treated. The combination of these treatments produces a "uniform brow-lift effect," he said.

Dr. Steinsapir estimated that his starting treatment of about 100 microdroplets (about 33 U) works well for about 70% of women and about 50% of men. Of 75 consecutive patients (56 of them women) that he has treated with this technique, 61 returned at 3-week follow-up and had no ptosis, he said.

Caution should be used in performing this technique on patients who have had aggressive upper eyelid surgery, because their anatomy is slightly different and they may be at higher risk for ptosis, especially if their eyelids are thin, Dr. Steinsapir advised.

"If your patients are used to other techniques, it's a tough road because this is a very different treatment paradigm," he said.

Dr. Steinsapir has filed for a patent on the method and has asserted a trademark for the term microdroplet. "If you adopt it in your practice, you'll have to come up with a different name for it," he said.

VAIL, COLO. — The superficial injection of many botulinum toxin type A microdroplets may create a more natural-looking brow lift than more aggressive treatment of the central frontalis and nearby depressor muscles, Dr. Kenneth D. Steinsapir said at a symposium sponsored by the American Academy of Facial Plastic and Reconstructive Surgery.

In the area where Dr. Steinsapir practices, a common technique for raising the brow includes botulinum toxin type A (Botox) injections to the central forehead (leaving the lateral frontalis alone), aggressive treatment of the corrugator and procerus muscles, and "pretty aggressive treatment" in the crow's feet area, he said.

This technique creates a central depression and smoothing of the forehead and significant, unopposed elevation of the frontalis, which produces a taut, arching central brow. Extreme versions of this have been given the moniker "Klingon forehead," said Dr. Steinsapir, a cosmetic, eye, and facial plastic surgeon in private practice in Los Angeles.

These patients have smoother horizontal forehead lines, but often at the expense of brow position depression in which the eyebrows crowd into the eyes.

"We have these treatment patterns because we're concerned that we'll get a ptosis after Botox treatment," he noted.

"Aesthetically, I think we can all agree that there is something not optimal about these faces," which are often seen in actresses, Dr. Steinsapir said. "This type of fakeness creates an impression in the public that Botox is a paralytic and undesirable at best."

"The key is, I think, to have a clearer picture of the anatomy and how these muscles interact," he continued.

"Brow position is really determined by the antagonists—the frontalis is really the only elevator in the brow. A substantial portion of the other muscles are brow depressors—the corrugators, the procerus, and the depressor supercilii," he said at the symposium, which was also sponsored by the American Society for Dermatologic Surgery and the American Society of Ophthalmic Plastic and Reconstructive Surgery.

To lessen the pronounced brow arch that occurs with that technique, Dr. Steinsapir developed his microdroplet technique, in which he aggressively treats the frontalis at and below the brow by injecting "smaller and smaller volumes of fluid in multiple locations." These microdroplets have volumes of 10–50 mcL of injectable saline; he has worked with microdroplets that contain 0.001–1 U Botox.

Dr. Steinsapir's currently preferred starting treatment is based on 100 U Botox and 3 mL of injectable saline, which equals about 0.33 U of Botox per 10 mcL.

He uses 32- and 33-gauge needles, which are more comfortable for the patient than a 30-gauge needle. He also uses magnification and subsurface illumination to see the subsurface vasculature "a little bit better," although he has not performed a study to determine if it reduces the rate of bruising, he said.

A typical treatment involves a total of about 100 microdroplets placed in double or triple rows just above, in, and below the brow, stopping around the level of the lowest brow cilia. The microdroplet injections are placed superficially about 1 mm into the skin to trap the Botox at the interface between the orbicularis oculi and the skin. For crow's feet, he will usually stop just before the midline of the lateral palpebral raphe. The glabellar area is also treated. The combination of these treatments produces a "uniform brow-lift effect," he said.

Dr. Steinsapir estimated that his starting treatment of about 100 microdroplets (about 33 U) works well for about 70% of women and about 50% of men. Of 75 consecutive patients (56 of them women) that he has treated with this technique, 61 returned at 3-week follow-up and had no ptosis, he said.

Caution should be used in performing this technique on patients who have had aggressive upper eyelid surgery, because their anatomy is slightly different and they may be at higher risk for ptosis, especially if their eyelids are thin, Dr. Steinsapir advised.

"If your patients are used to other techniques, it's a tough road because this is a very different treatment paradigm," he said.

Dr. Steinsapir has filed for a patent on the method and has asserted a trademark for the term microdroplet. "If you adopt it in your practice, you'll have to come up with a different name for it," he said.

VAIL, COLO. — The superficial injection of many botulinum toxin type A microdroplets may create a more natural-looking brow lift than more aggressive treatment of the central frontalis and nearby depressor muscles, Dr. Kenneth D. Steinsapir said at a symposium sponsored by the American Academy of Facial Plastic and Reconstructive Surgery.

In the area where Dr. Steinsapir practices, a common technique for raising the brow includes botulinum toxin type A (Botox) injections to the central forehead (leaving the lateral frontalis alone), aggressive treatment of the corrugator and procerus muscles, and "pretty aggressive treatment" in the crow's feet area, he said.

This technique creates a central depression and smoothing of the forehead and significant, unopposed elevation of the frontalis, which produces a taut, arching central brow. Extreme versions of this have been given the moniker "Klingon forehead," said Dr. Steinsapir, a cosmetic, eye, and facial plastic surgeon in private practice in Los Angeles.

These patients have smoother horizontal forehead lines, but often at the expense of brow position depression in which the eyebrows crowd into the eyes.

"We have these treatment patterns because we're concerned that we'll get a ptosis after Botox treatment," he noted.

"Aesthetically, I think we can all agree that there is something not optimal about these faces," which are often seen in actresses, Dr. Steinsapir said. "This type of fakeness creates an impression in the public that Botox is a paralytic and undesirable at best."

"The key is, I think, to have a clearer picture of the anatomy and how these muscles interact," he continued.

"Brow position is really determined by the antagonists—the frontalis is really the only elevator in the brow. A substantial portion of the other muscles are brow depressors—the corrugators, the procerus, and the depressor supercilii," he said at the symposium, which was also sponsored by the American Society for Dermatologic Surgery and the American Society of Ophthalmic Plastic and Reconstructive Surgery.

To lessen the pronounced brow arch that occurs with that technique, Dr. Steinsapir developed his microdroplet technique, in which he aggressively treats the frontalis at and below the brow by injecting "smaller and smaller volumes of fluid in multiple locations." These microdroplets have volumes of 10–50 mcL of injectable saline; he has worked with microdroplets that contain 0.001–1 U Botox.

Dr. Steinsapir's currently preferred starting treatment is based on 100 U Botox and 3 mL of injectable saline, which equals about 0.33 U of Botox per 10 mcL.

He uses 32- and 33-gauge needles, which are more comfortable for the patient than a 30-gauge needle. He also uses magnification and subsurface illumination to see the subsurface vasculature "a little bit better," although he has not performed a study to determine if it reduces the rate of bruising, he said.

A typical treatment involves a total of about 100 microdroplets placed in double or triple rows just above, in, and below the brow, stopping around the level of the lowest brow cilia. The microdroplet injections are placed superficially about 1 mm into the skin to trap the Botox at the interface between the orbicularis oculi and the skin. For crow's feet, he will usually stop just before the midline of the lateral palpebral raphe. The glabellar area is also treated. The combination of these treatments produces a "uniform brow-lift effect," he said.

Dr. Steinsapir estimated that his starting treatment of about 100 microdroplets (about 33 U) works well for about 70% of women and about 50% of men. Of 75 consecutive patients (56 of them women) that he has treated with this technique, 61 returned at 3-week follow-up and had no ptosis, he said.

Caution should be used in performing this technique on patients who have had aggressive upper eyelid surgery, because their anatomy is slightly different and they may be at higher risk for ptosis, especially if their eyelids are thin, Dr. Steinsapir advised.

"If your patients are used to other techniques, it's a tough road because this is a very different treatment paradigm," he said.

Dr. Steinsapir has filed for a patent on the method and has asserted a trademark for the term microdroplet. "If you adopt it in your practice, you'll have to come up with a different name for it," he said.

VAIL, COLO. — A bioengineered skin substitute may have applications in reconstructive surgery that extend beyond its indication for burn victims, Dr. Kapil Saigal said at a symposium sponsored by the American Academy of Facial Plastic and Reconstructive Surgery.

The recent development of biomaterials for head and neck reconstruction has provided alternatives to autologous skin transplantation, such as cadaveric allograft skin, xenografts, and bioengineered skin substitutes, said Dr. Saigal, a fourth-year resident in the department of otolaryngology-head and neck surgery at Jefferson Medical College, Philadelphia.

A biologic skin substitute can be used as a permanent replacement or as a temporary biologic dressing. These skin substitutes can decrease bacterial counts; slow the loss of water, proteins, and electro-lytes from the wound; reduce pain and fever; help restore function and facilitate early motion; and prevent desiccation of vessels, tendons, and nerves.

Fewer data are available on the functionality of biological skin substitutes in reconstructive surgery than in burn treatment and chronic wound healing, he said.

Integra artificial dermis is a composite bilayer dermal regeneration template that is used for skin replacement. It was approved by the Food and Drug Administration in 2003 for the treatment of life-threatening third-degree burns to provide immediate coverage for as much as 95% of body surface area.

The biomaterial is composed of a dermal replacement layer of a porous matrix of crosslinked bovine tendon collagen coated with a glycosaminoglycan (chondroitin-6-sulfate); a temporary epidermal layer of polysiloxane polymer (silicone) prevents moisture loss.

After Integra has been in place for 2–3 weeks, the template changes from its original color of pink to yellow or an orange-peach color, which indicates that the graft is vascularized and a new dermal-like layer has been generated. The epidermal polysiloxane layer can be removed so that a very thin epidermal autograft can be placed on the new dermis. Very little wound contraction occurs because of the thick dermal component, Dr. Saigal explained.

The template is thought to improve "fibroblast proliferation from the wound edges, while the addition of a glycosaminoglycan actually decreases the inflammatory component of wound healing and prevents the formation of granulation tissue," he said at the symposium, which also was sponsored by the American Society for Dermatologic Surgery and the American Society of Ophthalmic Plastic and Reconstructive Surgery.

Dr. Saigal reported that he and his associates have used Integra in 15 patients for wounds ranging from those on the eyelid to radiated scalp wounds with graft sizes of 10–140 cm

They have used the skin substitute to perform a delayed reconstruction after removal of a cutaneous malignancy, repair a defect after surgery for severe rhinophyma, cover wounds of the head and neck that were not amenable to primary or focal closure, and heal areas that have been irradiated or will be irradiated postoperatively. The product may be useful in closing wounds in children and elderly patients, he suggested.

In a case series of seven patients with an average age of 70 years who received the Integra artificial dermis, 100% of the split-thickness skin grafts that were applied after a mean of about 5 weeks survived without any complications (Plast. Reconstr. Surg. 2005;115:1010–7).

Other reports in the literature suggest that Integra has a better "take rate" in complicated wounds when it is combined with a vacuum-assisted closure or with fibrin glue, said Dr. Saigal, who disclosed that he and his colleagues have no financial interest in Integra.

Integra costs about $700–$900 per graft, he said.

VAIL, COLO. — A bioengineered skin substitute may have applications in reconstructive surgery that extend beyond its indication for burn victims, Dr. Kapil Saigal said at a symposium sponsored by the American Academy of Facial Plastic and Reconstructive Surgery.

The recent development of biomaterials for head and neck reconstruction has provided alternatives to autologous skin transplantation, such as cadaveric allograft skin, xenografts, and bioengineered skin substitutes, said Dr. Saigal, a fourth-year resident in the department of otolaryngology-head and neck surgery at Jefferson Medical College, Philadelphia.

A biologic skin substitute can be used as a permanent replacement or as a temporary biologic dressing. These skin substitutes can decrease bacterial counts; slow the loss of water, proteins, and electro-lytes from the wound; reduce pain and fever; help restore function and facilitate early motion; and prevent desiccation of vessels, tendons, and nerves.

Fewer data are available on the functionality of biological skin substitutes in reconstructive surgery than in burn treatment and chronic wound healing, he said.

Integra artificial dermis is a composite bilayer dermal regeneration template that is used for skin replacement. It was approved by the Food and Drug Administration in 2003 for the treatment of life-threatening third-degree burns to provide immediate coverage for as much as 95% of body surface area.

The biomaterial is composed of a dermal replacement layer of a porous matrix of crosslinked bovine tendon collagen coated with a glycosaminoglycan (chondroitin-6-sulfate); a temporary epidermal layer of polysiloxane polymer (silicone) prevents moisture loss.

After Integra has been in place for 2–3 weeks, the template changes from its original color of pink to yellow or an orange-peach color, which indicates that the graft is vascularized and a new dermal-like layer has been generated. The epidermal polysiloxane layer can be removed so that a very thin epidermal autograft can be placed on the new dermis. Very little wound contraction occurs because of the thick dermal component, Dr. Saigal explained.

The template is thought to improve "fibroblast proliferation from the wound edges, while the addition of a glycosaminoglycan actually decreases the inflammatory component of wound healing and prevents the formation of granulation tissue," he said at the symposium, which also was sponsored by the American Society for Dermatologic Surgery and the American Society of Ophthalmic Plastic and Reconstructive Surgery.

Dr. Saigal reported that he and his associates have used Integra in 15 patients for wounds ranging from those on the eyelid to radiated scalp wounds with graft sizes of 10–140 cm

They have used the skin substitute to perform a delayed reconstruction after removal of a cutaneous malignancy, repair a defect after surgery for severe rhinophyma, cover wounds of the head and neck that were not amenable to primary or focal closure, and heal areas that have been irradiated or will be irradiated postoperatively. The product may be useful in closing wounds in children and elderly patients, he suggested.

In a case series of seven patients with an average age of 70 years who received the Integra artificial dermis, 100% of the split-thickness skin grafts that were applied after a mean of about 5 weeks survived without any complications (Plast. Reconstr. Surg. 2005;115:1010–7).

Other reports in the literature suggest that Integra has a better "take rate" in complicated wounds when it is combined with a vacuum-assisted closure or with fibrin glue, said Dr. Saigal, who disclosed that he and his colleagues have no financial interest in Integra.

Integra costs about $700–$900 per graft, he said.

VAIL, COLO. — A bioengineered skin substitute may have applications in reconstructive surgery that extend beyond its indication for burn victims, Dr. Kapil Saigal said at a symposium sponsored by the American Academy of Facial Plastic and Reconstructive Surgery.

The recent development of biomaterials for head and neck reconstruction has provided alternatives to autologous skin transplantation, such as cadaveric allograft skin, xenografts, and bioengineered skin substitutes, said Dr. Saigal, a fourth-year resident in the department of otolaryngology-head and neck surgery at Jefferson Medical College, Philadelphia.

A biologic skin substitute can be used as a permanent replacement or as a temporary biologic dressing. These skin substitutes can decrease bacterial counts; slow the loss of water, proteins, and electro-lytes from the wound; reduce pain and fever; help restore function and facilitate early motion; and prevent desiccation of vessels, tendons, and nerves.

Fewer data are available on the functionality of biological skin substitutes in reconstructive surgery than in burn treatment and chronic wound healing, he said.

Integra artificial dermis is a composite bilayer dermal regeneration template that is used for skin replacement. It was approved by the Food and Drug Administration in 2003 for the treatment of life-threatening third-degree burns to provide immediate coverage for as much as 95% of body surface area.

The biomaterial is composed of a dermal replacement layer of a porous matrix of crosslinked bovine tendon collagen coated with a glycosaminoglycan (chondroitin-6-sulfate); a temporary epidermal layer of polysiloxane polymer (silicone) prevents moisture loss.

After Integra has been in place for 2–3 weeks, the template changes from its original color of pink to yellow or an orange-peach color, which indicates that the graft is vascularized and a new dermal-like layer has been generated. The epidermal polysiloxane layer can be removed so that a very thin epidermal autograft can be placed on the new dermis. Very little wound contraction occurs because of the thick dermal component, Dr. Saigal explained.

The template is thought to improve "fibroblast proliferation from the wound edges, while the addition of a glycosaminoglycan actually decreases the inflammatory component of wound healing and prevents the formation of granulation tissue," he said at the symposium, which also was sponsored by the American Society for Dermatologic Surgery and the American Society of Ophthalmic Plastic and Reconstructive Surgery.

Dr. Saigal reported that he and his associates have used Integra in 15 patients for wounds ranging from those on the eyelid to radiated scalp wounds with graft sizes of 10–140 cm

They have used the skin substitute to perform a delayed reconstruction after removal of a cutaneous malignancy, repair a defect after surgery for severe rhinophyma, cover wounds of the head and neck that were not amenable to primary or focal closure, and heal areas that have been irradiated or will be irradiated postoperatively. The product may be useful in closing wounds in children and elderly patients, he suggested.

In a case series of seven patients with an average age of 70 years who received the Integra artificial dermis, 100% of the split-thickness skin grafts that were applied after a mean of about 5 weeks survived without any complications (Plast. Reconstr. Surg. 2005;115:1010–7).

Other reports in the literature suggest that Integra has a better "take rate" in complicated wounds when it is combined with a vacuum-assisted closure or with fibrin glue, said Dr. Saigal, who disclosed that he and his colleagues have no financial interest in Integra.

Integra costs about $700–$900 per graft, he said.

ARLINGTON, VA. — Inadequate levels of vitamin D may help to explain not only morbidities such as osteoporosis but also less-appreciated effects of vitamin D insufficiency that worsen bodily functions and are commonly thought to be related to aging alone, Dr. Neil Binkley said at a conference sponsored by the American Society for Bone and Mineral Research.

“I would like to suggest to you that vitamin D inadequacy might be contributing to what we are currently accepting as old age-related morbidity,” said Dr. Binkley, who is the co-director of the University of Wisconsin Osteoporosis Clinical Center and Research Program, Madison.

The prevalence of densitometric osteopenia markedly increases with advancing age, and at any given bone density, age has a “profound impact” on the risk of fracture, he said (J. Clin. Invest. 1988;81:1804–9).

Many conditions other than osteoporosis that are affected by vitamin D status have been labeled as “age-related” morbidities, including the following:

▸ Sarcopenia. The expression of vitamin D receptors declines in muscle with aging. In muscle, vitamin D also may be involved with calcium transport and actin-myosin interaction.

A study of 1,008 older adults has suggested that vitamin D inadequacy is associated with sarcopenia. After a 3-year follow-up, men and women with baseline 25(OH)D levels less than 25 nmol/L were more than twice as likely to develop sarcopenia (based on either grip strength or muscle mass) than were those with a higher level of 25(OH)D (J. Clin. Endocrinol. Metab. 2003;88:5766–72).

▸ Falling. It is not known whether vitamin D status and muscle strength are causally related, but “it is, however, clear that vitamin D status is related to the risk of falling in both older men and older women,” Dr. Binkley said.

The risk of falling is increased by orthopedic disabilities, visual impairment, central or peripheral neurologic dysfunction, and muscle weakness, which may be the main risk factor, he said. A meta-analysis of double-blind, randomized, trials showed that vitamin D reduced the risk of falling by 22% (JAMA 2004;291:1999–2006).

▸ Overactive bladder. Bladder dysfunction also may be associated with muscle weakness, which can lead to poorer coordination of the muscles used to control urination. Overactive bladder affects 30%–40% of adults older than 75 years of age and two-thirds of nursing home residents; it is defined as urinary urgency with or without incontinence, usually with frequency and nocturia.

In a study of nearly 6,000 community-dwelling women aged 40 years or older, women in the highest quintiles of vitamin D intake had the lowest risk of developing overactive bladder (Neurourol. Urodyn. 2004;23:204–10).

▸ Difficulty swallowing. Up to 40% of individuals older than 60 years have problems swallowing, which can lead to undernutrition, sarcopenia, and aspiration pneumonia.

Dysphagia associated with aging classically has been felt to reflect neurologic disease such as Parkinson's or stroke, but more recent work has shown that even normal healthy adults swallow more slowly and generate lower tongue pressures than do younger adults.

“I think it's at least plausible that this decreased muscle function might be causally related to the increased risk of dysphagia observed with advancing age,” Dr. Binkley suggested.

But no research has been conducted on vitamin D status and the risk of dysphagia of aging, he said.

▸ Pulmonary function. Both the forced expiratory volume in the first second after a patient takes a deep breath and forced vital capacity are known to decline with aging; poor results on such tests are associated with substantial morbidity and mortality.

In a study of people in the National Health and Nutrition Examination Survey III (NHANES III) who were aged 60 years or older, both of those measures of lung function were significantly higher among people in the highest quintile of serum 25(OH)D concentration than it was in individuals in the lowest quintile of the vitamin (Chest 2005;128:3792–8).

Biologically plausible ways in which vitamin D might protect against a decline in pulmonary function include the possibility of a decline in respiratory muscle function with inadequate levels of vitamin D, lung tissue remodeling, or a reduction in airway inflammation.

▸ Age-related macular degeneration. In a yet-to-be published study involving 7,752 people who participated in NHANES III, the risk of developing age-related macular degeneration declined steadily from the lowest to the highest quintiles of serum 25(OH)D concentration.

▸ Dementia/cognitive decline. In a small case-control study, investigators found deficient and extremely low levels of vitamin D in significantly more ambulatory women with Alzheimer's disease than in control women of the same age without Alzheimer's or fractures (Bone 1998;23:555–7).

A poster that was presented at the conference showed that higher scores on the Mini-Mental State Examination in 32 patients in a memory clinic were significantly and positively correlated with higher vitamin D concentrations. In the observational study, 25(OH)D levels below 30 ng/mL—the generally recommended cutoff for vitamin D sufficiency—were detected in 25 patients.

The active vitamin D compound 1,25(OH)D is known to increase levels of choline acetyltransferase, which is involved in the synthesis of the neurotransmitter acetylcholine.

ARLINGTON, VA. — Inadequate levels of vitamin D may help to explain not only morbidities such as osteoporosis but also less-appreciated effects of vitamin D insufficiency that worsen bodily functions and are commonly thought to be related to aging alone, Dr. Neil Binkley said at a conference sponsored by the American Society for Bone and Mineral Research.

“I would like to suggest to you that vitamin D inadequacy might be contributing to what we are currently accepting as old age-related morbidity,” said Dr. Binkley, who is the co-director of the University of Wisconsin Osteoporosis Clinical Center and Research Program, Madison.

The prevalence of densitometric osteopenia markedly increases with advancing age, and at any given bone density, age has a “profound impact” on the risk of fracture, he said (J. Clin. Invest. 1988;81:1804–9).

Many conditions other than osteoporosis that are affected by vitamin D status have been labeled as “age-related” morbidities, including the following:

▸ Sarcopenia. The expression of vitamin D receptors declines in muscle with aging. In muscle, vitamin D also may be involved with calcium transport and actin-myosin interaction.

A study of 1,008 older adults has suggested that vitamin D inadequacy is associated with sarcopenia. After a 3-year follow-up, men and women with baseline 25(OH)D levels less than 25 nmol/L were more than twice as likely to develop sarcopenia (based on either grip strength or muscle mass) than were those with a higher level of 25(OH)D (J. Clin. Endocrinol. Metab. 2003;88:5766–72).

▸ Falling. It is not known whether vitamin D status and muscle strength are causally related, but “it is, however, clear that vitamin D status is related to the risk of falling in both older men and older women,” Dr. Binkley said.

The risk of falling is increased by orthopedic disabilities, visual impairment, central or peripheral neurologic dysfunction, and muscle weakness, which may be the main risk factor, he said. A meta-analysis of double-blind, randomized, trials showed that vitamin D reduced the risk of falling by 22% (JAMA 2004;291:1999–2006).

▸ Overactive bladder. Bladder dysfunction also may be associated with muscle weakness, which can lead to poorer coordination of the muscles used to control urination. Overactive bladder affects 30%–40% of adults older than 75 years of age and two-thirds of nursing home residents; it is defined as urinary urgency with or without incontinence, usually with frequency and nocturia.

In a study of nearly 6,000 community-dwelling women aged 40 years or older, women in the highest quintiles of vitamin D intake had the lowest risk of developing overactive bladder (Neurourol. Urodyn. 2004;23:204–10).

▸ Difficulty swallowing. Up to 40% of individuals older than 60 years have problems swallowing, which can lead to undernutrition, sarcopenia, and aspiration pneumonia.

Dysphagia associated with aging classically has been felt to reflect neurologic disease such as Parkinson's or stroke, but more recent work has shown that even normal healthy adults swallow more slowly and generate lower tongue pressures than do younger adults.

“I think it's at least plausible that this decreased muscle function might be causally related to the increased risk of dysphagia observed with advancing age,” Dr. Binkley suggested.

But no research has been conducted on vitamin D status and the risk of dysphagia of aging, he said.

▸ Pulmonary function. Both the forced expiratory volume in the first second after a patient takes a deep breath and forced vital capacity are known to decline with aging; poor results on such tests are associated with substantial morbidity and mortality.

In a study of people in the National Health and Nutrition Examination Survey III (NHANES III) who were aged 60 years or older, both of those measures of lung function were significantly higher among people in the highest quintile of serum 25(OH)D concentration than it was in individuals in the lowest quintile of the vitamin (Chest 2005;128:3792–8).

Biologically plausible ways in which vitamin D might protect against a decline in pulmonary function include the possibility of a decline in respiratory muscle function with inadequate levels of vitamin D, lung tissue remodeling, or a reduction in airway inflammation.

▸ Age-related macular degeneration. In a yet-to-be published study involving 7,752 people who participated in NHANES III, the risk of developing age-related macular degeneration declined steadily from the lowest to the highest quintiles of serum 25(OH)D concentration.

▸ Dementia/cognitive decline. In a small case-control study, investigators found deficient and extremely low levels of vitamin D in significantly more ambulatory women with Alzheimer's disease than in control women of the same age without Alzheimer's or fractures (Bone 1998;23:555–7).

A poster that was presented at the conference showed that higher scores on the Mini-Mental State Examination in 32 patients in a memory clinic were significantly and positively correlated with higher vitamin D concentrations. In the observational study, 25(OH)D levels below 30 ng/mL—the generally recommended cutoff for vitamin D sufficiency—were detected in 25 patients.

The active vitamin D compound 1,25(OH)D is known to increase levels of choline acetyltransferase, which is involved in the synthesis of the neurotransmitter acetylcholine.

ARLINGTON, VA. — Inadequate levels of vitamin D may help to explain not only morbidities such as osteoporosis but also less-appreciated effects of vitamin D insufficiency that worsen bodily functions and are commonly thought to be related to aging alone, Dr. Neil Binkley said at a conference sponsored by the American Society for Bone and Mineral Research.

“I would like to suggest to you that vitamin D inadequacy might be contributing to what we are currently accepting as old age-related morbidity,” said Dr. Binkley, who is the co-director of the University of Wisconsin Osteoporosis Clinical Center and Research Program, Madison.

The prevalence of densitometric osteopenia markedly increases with advancing age, and at any given bone density, age has a “profound impact” on the risk of fracture, he said (J. Clin. Invest. 1988;81:1804–9).

Many conditions other than osteoporosis that are affected by vitamin D status have been labeled as “age-related” morbidities, including the following:

▸ Sarcopenia. The expression of vitamin D receptors declines in muscle with aging. In muscle, vitamin D also may be involved with calcium transport and actin-myosin interaction.

A study of 1,008 older adults has suggested that vitamin D inadequacy is associated with sarcopenia. After a 3-year follow-up, men and women with baseline 25(OH)D levels less than 25 nmol/L were more than twice as likely to develop sarcopenia (based on either grip strength or muscle mass) than were those with a higher level of 25(OH)D (J. Clin. Endocrinol. Metab. 2003;88:5766–72).

▸ Falling. It is not known whether vitamin D status and muscle strength are causally related, but “it is, however, clear that vitamin D status is related to the risk of falling in both older men and older women,” Dr. Binkley said.

The risk of falling is increased by orthopedic disabilities, visual impairment, central or peripheral neurologic dysfunction, and muscle weakness, which may be the main risk factor, he said. A meta-analysis of double-blind, randomized, trials showed that vitamin D reduced the risk of falling by 22% (JAMA 2004;291:1999–2006).

▸ Overactive bladder. Bladder dysfunction also may be associated with muscle weakness, which can lead to poorer coordination of the muscles used to control urination. Overactive bladder affects 30%–40% of adults older than 75 years of age and two-thirds of nursing home residents; it is defined as urinary urgency with or without incontinence, usually with frequency and nocturia.

In a study of nearly 6,000 community-dwelling women aged 40 years or older, women in the highest quintiles of vitamin D intake had the lowest risk of developing overactive bladder (Neurourol. Urodyn. 2004;23:204–10).

▸ Difficulty swallowing. Up to 40% of individuals older than 60 years have problems swallowing, which can lead to undernutrition, sarcopenia, and aspiration pneumonia.

Dysphagia associated with aging classically has been felt to reflect neurologic disease such as Parkinson's or stroke, but more recent work has shown that even normal healthy adults swallow more slowly and generate lower tongue pressures than do younger adults.

“I think it's at least plausible that this decreased muscle function might be causally related to the increased risk of dysphagia observed with advancing age,” Dr. Binkley suggested.

But no research has been conducted on vitamin D status and the risk of dysphagia of aging, he said.

▸ Pulmonary function. Both the forced expiratory volume in the first second after a patient takes a deep breath and forced vital capacity are known to decline with aging; poor results on such tests are associated with substantial morbidity and mortality.

In a study of people in the National Health and Nutrition Examination Survey III (NHANES III) who were aged 60 years or older, both of those measures of lung function were significantly higher among people in the highest quintile of serum 25(OH)D concentration than it was in individuals in the lowest quintile of the vitamin (Chest 2005;128:3792–8).

Biologically plausible ways in which vitamin D might protect against a decline in pulmonary function include the possibility of a decline in respiratory muscle function with inadequate levels of vitamin D, lung tissue remodeling, or a reduction in airway inflammation.

▸ Age-related macular degeneration. In a yet-to-be published study involving 7,752 people who participated in NHANES III, the risk of developing age-related macular degeneration declined steadily from the lowest to the highest quintiles of serum 25(OH)D concentration.

▸ Dementia/cognitive decline. In a small case-control study, investigators found deficient and extremely low levels of vitamin D in significantly more ambulatory women with Alzheimer's disease than in control women of the same age without Alzheimer's or fractures (Bone 1998;23:555–7).

A poster that was presented at the conference showed that higher scores on the Mini-Mental State Examination in 32 patients in a memory clinic were significantly and positively correlated with higher vitamin D concentrations. In the observational study, 25(OH)D levels below 30 ng/mL—the generally recommended cutoff for vitamin D sufficiency—were detected in 25 patients.

The active vitamin D compound 1,25(OH)D is known to increase levels of choline acetyltransferase, which is involved in the synthesis of the neurotransmitter acetylcholine.

WASHINGTON — High temperature and humidity seem to increase the risk of recurrent gout attacks independently of other known risk factors, Yuqing Q. Zhang, D.Sc., reported at the annual meeting of the American College of Rheumatology.

“Although the pathophysiology of gout is well understood and efficacious clinical therapies are available, many patients with gout still suffer from recurrent gout attacks” brought on by certain risk factors, said Dr. Zhang of Boston University.

Decreases in intravascular volume from perspiration in hot, humid weather can result in high serum uric acid levels because of a reduction in uric acid excretion, Dr. Zhang said. Few studies have examined the link between risk factors for dehydration and the risk of recurrent gout attacks.

Dr. Zhang and his colleagues enrolled 197 patients with a median 5-year history of gout through an online advertisement. The patients answered a “hazard period” questionnaire on a Web site that asked about risk factors for gout attacks during the 2-day period before reporting an attack. They also filled out a control period questionnaire every 3 months for 1 year to provide data about time intervals between gout attacks. They were asked about medication use (such as diuretics), alcohol use, food intake (especially foods rich in purine or with little purine), and details of gout attacks when they occurred.

Weather information from more than 1,600 U.S. airports was provided by the Weather Underground Web site (www.wunderground.com

The relationship between the level of humidity during the 2 days before a gout attack and the risk of recurrent attacks followed the pattern for temperature very closely. High humidity seemed to be the strongest predictor for recurrent gout attacks, but very cold and dry weather also slightly increased the risk.

The findings were significant after controlling for medication use, alcohol consumption, and purine-rich food intake. Recurrent attacks were not associated with barometric pressure or precipitation.

WASHINGTON — High temperature and humidity seem to increase the risk of recurrent gout attacks independently of other known risk factors, Yuqing Q. Zhang, D.Sc., reported at the annual meeting of the American College of Rheumatology.

“Although the pathophysiology of gout is well understood and efficacious clinical therapies are available, many patients with gout still suffer from recurrent gout attacks” brought on by certain risk factors, said Dr. Zhang of Boston University.

Decreases in intravascular volume from perspiration in hot, humid weather can result in high serum uric acid levels because of a reduction in uric acid excretion, Dr. Zhang said. Few studies have examined the link between risk factors for dehydration and the risk of recurrent gout attacks.

Dr. Zhang and his colleagues enrolled 197 patients with a median 5-year history of gout through an online advertisement. The patients answered a “hazard period” questionnaire on a Web site that asked about risk factors for gout attacks during the 2-day period before reporting an attack. They also filled out a control period questionnaire every 3 months for 1 year to provide data about time intervals between gout attacks. They were asked about medication use (such as diuretics), alcohol use, food intake (especially foods rich in purine or with little purine), and details of gout attacks when they occurred.

Weather information from more than 1,600 U.S. airports was provided by the Weather Underground Web site (www.wunderground.com

The relationship between the level of humidity during the 2 days before a gout attack and the risk of recurrent attacks followed the pattern for temperature very closely. High humidity seemed to be the strongest predictor for recurrent gout attacks, but very cold and dry weather also slightly increased the risk.

The findings were significant after controlling for medication use, alcohol consumption, and purine-rich food intake. Recurrent attacks were not associated with barometric pressure or precipitation.

WASHINGTON — High temperature and humidity seem to increase the risk of recurrent gout attacks independently of other known risk factors, Yuqing Q. Zhang, D.Sc., reported at the annual meeting of the American College of Rheumatology.

“Although the pathophysiology of gout is well understood and efficacious clinical therapies are available, many patients with gout still suffer from recurrent gout attacks” brought on by certain risk factors, said Dr. Zhang of Boston University.

Decreases in intravascular volume from perspiration in hot, humid weather can result in high serum uric acid levels because of a reduction in uric acid excretion, Dr. Zhang said. Few studies have examined the link between risk factors for dehydration and the risk of recurrent gout attacks.

Dr. Zhang and his colleagues enrolled 197 patients with a median 5-year history of gout through an online advertisement. The patients answered a “hazard period” questionnaire on a Web site that asked about risk factors for gout attacks during the 2-day period before reporting an attack. They also filled out a control period questionnaire every 3 months for 1 year to provide data about time intervals between gout attacks. They were asked about medication use (such as diuretics), alcohol use, food intake (especially foods rich in purine or with little purine), and details of gout attacks when they occurred.

Weather information from more than 1,600 U.S. airports was provided by the Weather Underground Web site (www.wunderground.com

The relationship between the level of humidity during the 2 days before a gout attack and the risk of recurrent attacks followed the pattern for temperature very closely. High humidity seemed to be the strongest predictor for recurrent gout attacks, but very cold and dry weather also slightly increased the risk.

The findings were significant after controlling for medication use, alcohol consumption, and purine-rich food intake. Recurrent attacks were not associated with barometric pressure or precipitation.

ARLINGTON, VA. — A level of vitamin D that is low but near or within the normal range may mask the presentation of patients with primary hyperparathyroidism, Dr. Shonni J. Silverberg reported at a conference sponsored by the American Society for Bone and Mineral Research.

In the United States, the presentation and epidemiology of primary hyperparathyroidism (pHPT) and vitamin D deficiency have developed concomitantly since food began to be fortified with vitamin D about 75 years ago. During this period, the prevalence of vitamin D deficiency has declined dramatically while the clinical manifestations of pHPT have become less severe. Symptomatic pHPT, or osteitis fibrosa cystica, has decreased because of lower levels of parathyroid hormone (PTH) in the disease. The weight and size of parathyroid adenomas also has declined substantially during this period, said Dr. Silverberg, professor of clinical medicine at Columbia University in New York.

“The question [was] whether or not calcium and vitamin D nutrition affects clinical expression of tumor growth in primary hyperparathyroidism. There has long been a hypothesis of 'double trouble,' which states that the clinical manifestations of primary hyperparathyroidism may be more severe in the presence of vitamin D deficiency,” she said.

Epidemiologic data show that classical pHPT still exists in areas of the world where vitamin D deficiency is endemic. When one analyzes the relationship between the two conditions in the United States and in developing countries where vitamin D deficiency is endemic, vitamin D (25-hydroxyvitamin D) levels are “somewhat inversely proportional” to the degree of PTH elevation, according to Dr. Silverberg. In this situation, people with very low vitamin D levels and pHPT may have PTH levels 15–20 times the upper limit of normal, but those with higher vitamin D levels—while still being in the lower range of normal—and pHPT may have PTH levels 1.5–2 times the upper limit of normal.

In patients with mild pHPT, sufficient—but still low-normal—levels of vitamin D oppose the hypercalcemic effect of excess PTH and thereby lower serum calcium levels and urinary calcium excretion back to their normal ranges.

Many of these people may be referred from doctors in the community who are reluctant to make a diagnosis of pHPT in patients with an elevated PTH level, normal serum calcium level, and a sufficient level of vitamin D, Dr. Silverberg said.

A study of women in New York and Beijing found that nearly all New Yorkers with pHPT were asymptomatic, whereas 94% of women with pHPT in Beijing were symptomatic and often had fractures and severe bone disease. There were very marked differences in serum levels of calcium, PTH, and vitamin D levels between women in the two cities (Int. J. Fertil. Womens Med. 2000;45:158–65).

In a study of 49 patients in Saudi Arabia (where vitamin D deficiency is endemic) who underwent a parathyroidectomy for pHPT, 19 patients had severe bone disease. These 19 patients had high levels of PTH and alkaline phosphatase, and increased thyroid gland size and weight, but their vitamin D levels were not significantly different from those without severe bone disease. The study investigators concluded that marked vitamin D deficiency may play a part in osteitis fibrosa cystica, but manifestation of bone disease with pHPT is multifactorial (J. Endocrinol. Invest. 2004;27:807–12).

A study in France showed that 38% of normal individuals were vitamin D insufficient (using a 20-ng/mL cutoff), compared with 91% of those with pHPT, regardless of its severity. The proportion of patients with pHPT who had vitamin D insufficiency also was similar regardless of whether their serum calcium level was lower or greater than 12 mg/dL (J. Endocrinol. Invest. 2006;29:511–5).

These results raise the question of whether there is a cutoff level of vitamin D at which pHPT becomes symptomatic, Dr. Silverberg said.

A study of patients with pHPT in Turkey found that individuals with vitamin D levels less than 15 ng/mL had significantly higher serum PTH, alkaline phosphatase, and parathyroid adenoma weight than did those with vitamin D levels of 15–25 ng/mL or more than 25 ng/mL (World J. Surg. 2006;30:321–6). Similar results were found in a study of U.S. patients.

The investigators of a separate case-control study that controlled for the effects of age, sex, body mass index, and season corroborated the finding that low vitamin D levels could worsen the clinical presentation of pHPT, but they did not find any association between low vitamin D levels and thyroid adenoma size. The percentage of patients with a vitamin D level less than 20 ng/mL varied significantly between the summer and winter months in the study's two control groups, but not among patients with pHPT (Clin. Endocrinol. [Oxf.] 2005;63:506–13).

Dr. Silverberg and her colleagues found that 53% of 124 U.S. patients with mild pHPT had an insufficient level of vitamin D (less than 20 ng/mL). The researchers also noticed a seasonal variation in the manifestation of pHPT in the summer in which vitamin D levels rose while PTH levels dropped. When the patients were split into tertiles based on vitamin D levels, the investigators found that serum PTH levels and alkaline phosphatase activity were significantly higher among patients in the lowest tertile of vitamin D (less than 16 ng/mL) than in patients in the middle (16–24 ng/mL) and highest tertiles (more than 24 ng/mL). Another analysis of the same data suggested that the relationship was valid throughout the range of levels for vitamin D and serum PTH. Histomorphometric studies of the patients' bones also were consistent with an enhanced effect of PTH in those with a low level of vitamin D (Am. J. Med. 1999;107:561–7). “It is very important, however, to remember that the results we are describing are [cross-sectional] … and that there is absolutely no way, based on anything that we or anybody else knows at this point, to infer a causal association in these data,” she said.

But another study of women with pHPT did not find any association between vitamin D levels and the severity of pHPT. In that study, low vitamin D levels were associated with age and renal function, but there was no association between vitamin D level and bone mineral density after investigators controlled for age, PTH excess, and body mass index (Clin. Endocrinol. [Oxf.] 2004;60:81–6).

The surgical literature shows that after patients with pHPT undergo a parathyroidectomy, a substantial percentage of patients have persistently elevated PTH levels despite others signs of being cured of their hyperparathyroidism. The most consistent finding across these studies is low vitamin D levels either just before or immediately after surgery. In this case, pHPT has become secondary HPT, she noted.

One small study of vitamin D repletion in patients with suspected pHPT did not provide conclusive results. In a study of 229 patients with osteoporosis, 15 had low vitamin D levels and concomitant high PTH levels (J. Clin. Endocrinol. Metab. 2000;85:3541–3). After a single treatment of 500,000 U of vitamin D₂, five patients still had elevated PTH levels and were presumed to have pHPT. But two of those five patients had serum calcium levels less than 9 mg/dL, “which certainly raises the question in my mind about the diagnosis,” Dr. Silverberg said.

In those five patients, the bone mineral density after 13 months had increased by 6% in the spine and 8% in the hip. Although the investigators concluded that the increase in BMD resulted from the effect of vitamin D on pHPT, the patients' calcium levels make the diagnosis of pHPT questionable, she said.

ARLINGTON, VA. — A level of vitamin D that is low but near or within the normal range may mask the presentation of patients with primary hyperparathyroidism, Dr. Shonni J. Silverberg reported at a conference sponsored by the American Society for Bone and Mineral Research.

In the United States, the presentation and epidemiology of primary hyperparathyroidism (pHPT) and vitamin D deficiency have developed concomitantly since food began to be fortified with vitamin D about 75 years ago. During this period, the prevalence of vitamin D deficiency has declined dramatically while the clinical manifestations of pHPT have become less severe. Symptomatic pHPT, or osteitis fibrosa cystica, has decreased because of lower levels of parathyroid hormone (PTH) in the disease. The weight and size of parathyroid adenomas also has declined substantially during this period, said Dr. Silverberg, professor of clinical medicine at Columbia University in New York.

“The question [was] whether or not calcium and vitamin D nutrition affects clinical expression of tumor growth in primary hyperparathyroidism. There has long been a hypothesis of 'double trouble,' which states that the clinical manifestations of primary hyperparathyroidism may be more severe in the presence of vitamin D deficiency,” she said.

Epidemiologic data show that classical pHPT still exists in areas of the world where vitamin D deficiency is endemic. When one analyzes the relationship between the two conditions in the United States and in developing countries where vitamin D deficiency is endemic, vitamin D (25-hydroxyvitamin D) levels are “somewhat inversely proportional” to the degree of PTH elevation, according to Dr. Silverberg. In this situation, people with very low vitamin D levels and pHPT may have PTH levels 15–20 times the upper limit of normal, but those with higher vitamin D levels—while still being in the lower range of normal—and pHPT may have PTH levels 1.5–2 times the upper limit of normal.

In patients with mild pHPT, sufficient—but still low-normal—levels of vitamin D oppose the hypercalcemic effect of excess PTH and thereby lower serum calcium levels and urinary calcium excretion back to their normal ranges.

Many of these people may be referred from doctors in the community who are reluctant to make a diagnosis of pHPT in patients with an elevated PTH level, normal serum calcium level, and a sufficient level of vitamin D, Dr. Silverberg said.

A study of women in New York and Beijing found that nearly all New Yorkers with pHPT were asymptomatic, whereas 94% of women with pHPT in Beijing were symptomatic and often had fractures and severe bone disease. There were very marked differences in serum levels of calcium, PTH, and vitamin D levels between women in the two cities (Int. J. Fertil. Womens Med. 2000;45:158–65).

In a study of 49 patients in Saudi Arabia (where vitamin D deficiency is endemic) who underwent a parathyroidectomy for pHPT, 19 patients had severe bone disease. These 19 patients had high levels of PTH and alkaline phosphatase, and increased thyroid gland size and weight, but their vitamin D levels were not significantly different from those without severe bone disease. The study investigators concluded that marked vitamin D deficiency may play a part in osteitis fibrosa cystica, but manifestation of bone disease with pHPT is multifactorial (J. Endocrinol. Invest. 2004;27:807–12).

A study in France showed that 38% of normal individuals were vitamin D insufficient (using a 20-ng/mL cutoff), compared with 91% of those with pHPT, regardless of its severity. The proportion of patients with pHPT who had vitamin D insufficiency also was similar regardless of whether their serum calcium level was lower or greater than 12 mg/dL (J. Endocrinol. Invest. 2006;29:511–5).

These results raise the question of whether there is a cutoff level of vitamin D at which pHPT becomes symptomatic, Dr. Silverberg said.

A study of patients with pHPT in Turkey found that individuals with vitamin D levels less than 15 ng/mL had significantly higher serum PTH, alkaline phosphatase, and parathyroid adenoma weight than did those with vitamin D levels of 15–25 ng/mL or more than 25 ng/mL (World J. Surg. 2006;30:321–6). Similar results were found in a study of U.S. patients.

The investigators of a separate case-control study that controlled for the effects of age, sex, body mass index, and season corroborated the finding that low vitamin D levels could worsen the clinical presentation of pHPT, but they did not find any association between low vitamin D levels and thyroid adenoma size. The percentage of patients with a vitamin D level less than 20 ng/mL varied significantly between the summer and winter months in the study's two control groups, but not among patients with pHPT (Clin. Endocrinol. [Oxf.] 2005;63:506–13).

Dr. Silverberg and her colleagues found that 53% of 124 U.S. patients with mild pHPT had an insufficient level of vitamin D (less than 20 ng/mL). The researchers also noticed a seasonal variation in the manifestation of pHPT in the summer in which vitamin D levels rose while PTH levels dropped. When the patients were split into tertiles based on vitamin D levels, the investigators found that serum PTH levels and alkaline phosphatase activity were significantly higher among patients in the lowest tertile of vitamin D (less than 16 ng/mL) than in patients in the middle (16–24 ng/mL) and highest tertiles (more than 24 ng/mL). Another analysis of the same data suggested that the relationship was valid throughout the range of levels for vitamin D and serum PTH. Histomorphometric studies of the patients' bones also were consistent with an enhanced effect of PTH in those with a low level of vitamin D (Am. J. Med. 1999;107:561–7). “It is very important, however, to remember that the results we are describing are [cross-sectional] … and that there is absolutely no way, based on anything that we or anybody else knows at this point, to infer a causal association in these data,” she said.

But another study of women with pHPT did not find any association between vitamin D levels and the severity of pHPT. In that study, low vitamin D levels were associated with age and renal function, but there was no association between vitamin D level and bone mineral density after investigators controlled for age, PTH excess, and body mass index (Clin. Endocrinol. [Oxf.] 2004;60:81–6).

The surgical literature shows that after patients with pHPT undergo a parathyroidectomy, a substantial percentage of patients have persistently elevated PTH levels despite others signs of being cured of their hyperparathyroidism. The most consistent finding across these studies is low vitamin D levels either just before or immediately after surgery. In this case, pHPT has become secondary HPT, she noted.

One small study of vitamin D repletion in patients with suspected pHPT did not provide conclusive results. In a study of 229 patients with osteoporosis, 15 had low vitamin D levels and concomitant high PTH levels (J. Clin. Endocrinol. Metab. 2000;85:3541–3). After a single treatment of 500,000 U of vitamin D₂, five patients still had elevated PTH levels and were presumed to have pHPT. But two of those five patients had serum calcium levels less than 9 mg/dL, “which certainly raises the question in my mind about the diagnosis,” Dr. Silverberg said.

In those five patients, the bone mineral density after 13 months had increased by 6% in the spine and 8% in the hip. Although the investigators concluded that the increase in BMD resulted from the effect of vitamin D on pHPT, the patients' calcium levels make the diagnosis of pHPT questionable, she said.

ARLINGTON, VA. — A level of vitamin D that is low but near or within the normal range may mask the presentation of patients with primary hyperparathyroidism, Dr. Shonni J. Silverberg reported at a conference sponsored by the American Society for Bone and Mineral Research.

In the United States, the presentation and epidemiology of primary hyperparathyroidism (pHPT) and vitamin D deficiency have developed concomitantly since food began to be fortified with vitamin D about 75 years ago. During this period, the prevalence of vitamin D deficiency has declined dramatically while the clinical manifestations of pHPT have become less severe. Symptomatic pHPT, or osteitis fibrosa cystica, has decreased because of lower levels of parathyroid hormone (PTH) in the disease. The weight and size of parathyroid adenomas also has declined substantially during this period, said Dr. Silverberg, professor of clinical medicine at Columbia University in New York.

“The question [was] whether or not calcium and vitamin D nutrition affects clinical expression of tumor growth in primary hyperparathyroidism. There has long been a hypothesis of 'double trouble,' which states that the clinical manifestations of primary hyperparathyroidism may be more severe in the presence of vitamin D deficiency,” she said.

Epidemiologic data show that classical pHPT still exists in areas of the world where vitamin D deficiency is endemic. When one analyzes the relationship between the two conditions in the United States and in developing countries where vitamin D deficiency is endemic, vitamin D (25-hydroxyvitamin D) levels are “somewhat inversely proportional” to the degree of PTH elevation, according to Dr. Silverberg. In this situation, people with very low vitamin D levels and pHPT may have PTH levels 15–20 times the upper limit of normal, but those with higher vitamin D levels—while still being in the lower range of normal—and pHPT may have PTH levels 1.5–2 times the upper limit of normal.

In patients with mild pHPT, sufficient—but still low-normal—levels of vitamin D oppose the hypercalcemic effect of excess PTH and thereby lower serum calcium levels and urinary calcium excretion back to their normal ranges.

Many of these people may be referred from doctors in the community who are reluctant to make a diagnosis of pHPT in patients with an elevated PTH level, normal serum calcium level, and a sufficient level of vitamin D, Dr. Silverberg said.

A study of women in New York and Beijing found that nearly all New Yorkers with pHPT were asymptomatic, whereas 94% of women with pHPT in Beijing were symptomatic and often had fractures and severe bone disease. There were very marked differences in serum levels of calcium, PTH, and vitamin D levels between women in the two cities (Int. J. Fertil. Womens Med. 2000;45:158–65).

In a study of 49 patients in Saudi Arabia (where vitamin D deficiency is endemic) who underwent a parathyroidectomy for pHPT, 19 patients had severe bone disease. These 19 patients had high levels of PTH and alkaline phosphatase, and increased thyroid gland size and weight, but their vitamin D levels were not significantly different from those without severe bone disease. The study investigators concluded that marked vitamin D deficiency may play a part in osteitis fibrosa cystica, but manifestation of bone disease with pHPT is multifactorial (J. Endocrinol. Invest. 2004;27:807–12).

A study in France showed that 38% of normal individuals were vitamin D insufficient (using a 20-ng/mL cutoff), compared with 91% of those with pHPT, regardless of its severity. The proportion of patients with pHPT who had vitamin D insufficiency also was similar regardless of whether their serum calcium level was lower or greater than 12 mg/dL (J. Endocrinol. Invest. 2006;29:511–5).

These results raise the question of whether there is a cutoff level of vitamin D at which pHPT becomes symptomatic, Dr. Silverberg said.

A study of patients with pHPT in Turkey found that individuals with vitamin D levels less than 15 ng/mL had significantly higher serum PTH, alkaline phosphatase, and parathyroid adenoma weight than did those with vitamin D levels of 15–25 ng/mL or more than 25 ng/mL (World J. Surg. 2006;30:321–6). Similar results were found in a study of U.S. patients.

The investigators of a separate case-control study that controlled for the effects of age, sex, body mass index, and season corroborated the finding that low vitamin D levels could worsen the clinical presentation of pHPT, but they did not find any association between low vitamin D levels and thyroid adenoma size. The percentage of patients with a vitamin D level less than 20 ng/mL varied significantly between the summer and winter months in the study's two control groups, but not among patients with pHPT (Clin. Endocrinol. [Oxf.] 2005;63:506–13).

Dr. Silverberg and her colleagues found that 53% of 124 U.S. patients with mild pHPT had an insufficient level of vitamin D (less than 20 ng/mL). The researchers also noticed a seasonal variation in the manifestation of pHPT in the summer in which vitamin D levels rose while PTH levels dropped. When the patients were split into tertiles based on vitamin D levels, the investigators found that serum PTH levels and alkaline phosphatase activity were significantly higher among patients in the lowest tertile of vitamin D (less than 16 ng/mL) than in patients in the middle (16–24 ng/mL) and highest tertiles (more than 24 ng/mL). Another analysis of the same data suggested that the relationship was valid throughout the range of levels for vitamin D and serum PTH. Histomorphometric studies of the patients' bones also were consistent with an enhanced effect of PTH in those with a low level of vitamin D (Am. J. Med. 1999;107:561–7). “It is very important, however, to remember that the results we are describing are [cross-sectional] … and that there is absolutely no way, based on anything that we or anybody else knows at this point, to infer a causal association in these data,” she said.

But another study of women with pHPT did not find any association between vitamin D levels and the severity of pHPT. In that study, low vitamin D levels were associated with age and renal function, but there was no association between vitamin D level and bone mineral density after investigators controlled for age, PTH excess, and body mass index (Clin. Endocrinol. [Oxf.] 2004;60:81–6).

The surgical literature shows that after patients with pHPT undergo a parathyroidectomy, a substantial percentage of patients have persistently elevated PTH levels despite others signs of being cured of their hyperparathyroidism. The most consistent finding across these studies is low vitamin D levels either just before or immediately after surgery. In this case, pHPT has become secondary HPT, she noted.

One small study of vitamin D repletion in patients with suspected pHPT did not provide conclusive results. In a study of 229 patients with osteoporosis, 15 had low vitamin D levels and concomitant high PTH levels (J. Clin. Endocrinol. Metab. 2000;85:3541–3). After a single treatment of 500,000 U of vitamin D₂, five patients still had elevated PTH levels and were presumed to have pHPT. But two of those five patients had serum calcium levels less than 9 mg/dL, “which certainly raises the question in my mind about the diagnosis,” Dr. Silverberg said.

In those five patients, the bone mineral density after 13 months had increased by 6% in the spine and 8% in the hip. Although the investigators concluded that the increase in BMD resulted from the effect of vitamin D on pHPT, the patients' calcium levels make the diagnosis of pHPT questionable, she said.

WASHINGTON — Atherosclerosis is more likely to progress in systemic lupus erythematosus patients when lupus is diagnosed at older ages or has existed for a long duration, and when high homocysteine levels are present, according to new research presented at the annual meeting of the American College of Rheumatology.

Other data at the meeting suggested the risk that women with SLE will develop carotid artery plaque may be determined by the presence of proinflammatory high-density lipoprotein (piHDL) cholesterol.

“We really don't know the rate and determinants of progression of carotid plaque in lupus,” said Dr. Mary J. Roman of Cornell University, New York. She and her colleagues used serial ultrasound scans of the distal carotid artery and clinical assessments to evaluate the progression of atherosclerosis in 159 patients in the Hospital for Special Surgery's SLE registry.

After an average follow-up of 34 months, 28% of the patients had either developed first-time atherosclerotic plaque in the carotid since their baseline assessment or showed an increase in existing plaque since baseline. That is equivalent to progression of atherosclerosis in about 10% of SLE patients per year, Dr. Roman said. “We may use this observed rate of atherosclerosis progression in assessing the efficacy in future intervention trials.”

Compared with patients who had progressive plaque build up, those without plaque progression were significantly younger at baseline (mean age 50 years vs. 36 years) and at diagnosis (mean 36 years vs. 21 years), as well as lower serum homocysteine levels at baseline. Patients without progression of atherosclerosis tended to have more aggressive treatment of disease than those with progression.

For each 10-year incremental increase in either age at diagnosis or disease duration, patients were about 3 times more likely to have plaque progression than no plaque or stable plaque. Progression of atherosclerosis occurred in 56% of patients in the highest tertile of baseline serum homocysteine levels (7.9 micromol/L or greater).

“Other than older age, traditional risk factors were not associated with progression of atherosclerosis,” Dr. Roman noted.

In a separate presentation, Dr. Maureen McMahon of the department of rheumatology at the University of California at Los Angeles reported preliminary data from an ongoing study suggesting the development of carotid artery plaque in women with SLE is associated with the presence of piHDL.

After conducting B-mode ultrasound screening of the carotid artery and taking blood samples of women with SLE and healthy control women, Dr. McMahon and her colleagues found that 42 of 95 (44%) women with SLE had piHDL, compared with 3 of 52 (6%) age-matched control women. Significantly more SLE patients with carotid plaque had piHDL than did SLE patients without plaque (93% vs. 38%). But there was no significant difference in the presence of piHDL between control patients with and without plaque.

Oxidized low-density lipoprotein (LDL cholesterol) directly and indirectly promotes the production of inflammatory cytokines, the migration of monocytes into the subepithelial space of vessels, and the formation of macrophages that take up the oxidized LDL cholesterol and form foam cells that build an atherosclerotic plaque. Normal HDL cholesterol helps to reduce the effect of oxidized LDL cholesterol by promoting cholesterol efflux from cells and by inhibiting the oxidization of LDL cholesterol. During periods of acute inflammation, HDL cholesterol may become proinflammatory and unable to perform its usual protective function, she explained.

SLE patients with piHDL were 25 times more likely than control patients to have plaque after controlling for the traditional cardiovascular risk factors of hypertension, elevated LDL cholesterol, age, body mass index, diabetes, and high-sensitivity C-reactive protein. “Measurement of piHDL may be one tool to identify [SLE] patients at risk for the development of atherosclerosis,” Dr. McMahon concluded.

The SLE patients had a mean age of about 43 years and were not selected for a history of cardiovascular disease. They were not allowed to take statins within 6 months of entry into the study.

WASHINGTON — Atherosclerosis is more likely to progress in systemic lupus erythematosus patients when lupus is diagnosed at older ages or has existed for a long duration, and when high homocysteine levels are present, according to new research presented at the annual meeting of the American College of Rheumatology.

Other data at the meeting suggested the risk that women with SLE will develop carotid artery plaque may be determined by the presence of proinflammatory high-density lipoprotein (piHDL) cholesterol.

“We really don't know the rate and determinants of progression of carotid plaque in lupus,” said Dr. Mary J. Roman of Cornell University, New York. She and her colleagues used serial ultrasound scans of the distal carotid artery and clinical assessments to evaluate the progression of atherosclerosis in 159 patients in the Hospital for Special Surgery's SLE registry.

After an average follow-up of 34 months, 28% of the patients had either developed first-time atherosclerotic plaque in the carotid since their baseline assessment or showed an increase in existing plaque since baseline. That is equivalent to progression of atherosclerosis in about 10% of SLE patients per year, Dr. Roman said. “We may use this observed rate of atherosclerosis progression in assessing the efficacy in future intervention trials.”

Compared with patients who had progressive plaque build up, those without plaque progression were significantly younger at baseline (mean age 50 years vs. 36 years) and at diagnosis (mean 36 years vs. 21 years), as well as lower serum homocysteine levels at baseline. Patients without progression of atherosclerosis tended to have more aggressive treatment of disease than those with progression.

For each 10-year incremental increase in either age at diagnosis or disease duration, patients were about 3 times more likely to have plaque progression than no plaque or stable plaque. Progression of atherosclerosis occurred in 56% of patients in the highest tertile of baseline serum homocysteine levels (7.9 micromol/L or greater).

“Other than older age, traditional risk factors were not associated with progression of atherosclerosis,” Dr. Roman noted.

In a separate presentation, Dr. Maureen McMahon of the department of rheumatology at the University of California at Los Angeles reported preliminary data from an ongoing study suggesting the development of carotid artery plaque in women with SLE is associated with the presence of piHDL.

After conducting B-mode ultrasound screening of the carotid artery and taking blood samples of women with SLE and healthy control women, Dr. McMahon and her colleagues found that 42 of 95 (44%) women with SLE had piHDL, compared with 3 of 52 (6%) age-matched control women. Significantly more SLE patients with carotid plaque had piHDL than did SLE patients without plaque (93% vs. 38%). But there was no significant difference in the presence of piHDL between control patients with and without plaque.

Oxidized low-density lipoprotein (LDL cholesterol) directly and indirectly promotes the production of inflammatory cytokines, the migration of monocytes into the subepithelial space of vessels, and the formation of macrophages that take up the oxidized LDL cholesterol and form foam cells that build an atherosclerotic plaque. Normal HDL cholesterol helps to reduce the effect of oxidized LDL cholesterol by promoting cholesterol efflux from cells and by inhibiting the oxidization of LDL cholesterol. During periods of acute inflammation, HDL cholesterol may become proinflammatory and unable to perform its usual protective function, she explained.

SLE patients with piHDL were 25 times more likely than control patients to have plaque after controlling for the traditional cardiovascular risk factors of hypertension, elevated LDL cholesterol, age, body mass index, diabetes, and high-sensitivity C-reactive protein. “Measurement of piHDL may be one tool to identify [SLE] patients at risk for the development of atherosclerosis,” Dr. McMahon concluded.

The SLE patients had a mean age of about 43 years and were not selected for a history of cardiovascular disease. They were not allowed to take statins within 6 months of entry into the study.

WASHINGTON — Atherosclerosis is more likely to progress in systemic lupus erythematosus patients when lupus is diagnosed at older ages or has existed for a long duration, and when high homocysteine levels are present, according to new research presented at the annual meeting of the American College of Rheumatology.

Other data at the meeting suggested the risk that women with SLE will develop carotid artery plaque may be determined by the presence of proinflammatory high-density lipoprotein (piHDL) cholesterol.

“We really don't know the rate and determinants of progression of carotid plaque in lupus,” said Dr. Mary J. Roman of Cornell University, New York. She and her colleagues used serial ultrasound scans of the distal carotid artery and clinical assessments to evaluate the progression of atherosclerosis in 159 patients in the Hospital for Special Surgery's SLE registry.

After an average follow-up of 34 months, 28% of the patients had either developed first-time atherosclerotic plaque in the carotid since their baseline assessment or showed an increase in existing plaque since baseline. That is equivalent to progression of atherosclerosis in about 10% of SLE patients per year, Dr. Roman said. “We may use this observed rate of atherosclerosis progression in assessing the efficacy in future intervention trials.”

Compared with patients who had progressive plaque build up, those without plaque progression were significantly younger at baseline (mean age 50 years vs. 36 years) and at diagnosis (mean 36 years vs. 21 years), as well as lower serum homocysteine levels at baseline. Patients without progression of atherosclerosis tended to have more aggressive treatment of disease than those with progression.

For each 10-year incremental increase in either age at diagnosis or disease duration, patients were about 3 times more likely to have plaque progression than no plaque or stable plaque. Progression of atherosclerosis occurred in 56% of patients in the highest tertile of baseline serum homocysteine levels (7.9 micromol/L or greater).

“Other than older age, traditional risk factors were not associated with progression of atherosclerosis,” Dr. Roman noted.

In a separate presentation, Dr. Maureen McMahon of the department of rheumatology at the University of California at Los Angeles reported preliminary data from an ongoing study suggesting the development of carotid artery plaque in women with SLE is associated with the presence of piHDL.

After conducting B-mode ultrasound screening of the carotid artery and taking blood samples of women with SLE and healthy control women, Dr. McMahon and her colleagues found that 42 of 95 (44%) women with SLE had piHDL, compared with 3 of 52 (6%) age-matched control women. Significantly more SLE patients with carotid plaque had piHDL than did SLE patients without plaque (93% vs. 38%). But there was no significant difference in the presence of piHDL between control patients with and without plaque.

Oxidized low-density lipoprotein (LDL cholesterol) directly and indirectly promotes the production of inflammatory cytokines, the migration of monocytes into the subepithelial space of vessels, and the formation of macrophages that take up the oxidized LDL cholesterol and form foam cells that build an atherosclerotic plaque. Normal HDL cholesterol helps to reduce the effect of oxidized LDL cholesterol by promoting cholesterol efflux from cells and by inhibiting the oxidization of LDL cholesterol. During periods of acute inflammation, HDL cholesterol may become proinflammatory and unable to perform its usual protective function, she explained.

SLE patients with piHDL were 25 times more likely than control patients to have plaque after controlling for the traditional cardiovascular risk factors of hypertension, elevated LDL cholesterol, age, body mass index, diabetes, and high-sensitivity C-reactive protein. “Measurement of piHDL may be one tool to identify [SLE] patients at risk for the development of atherosclerosis,” Dr. McMahon concluded.

The SLE patients had a mean age of about 43 years and were not selected for a history of cardiovascular disease. They were not allowed to take statins within 6 months of entry into the study.

ARLINGTON, VA. — Pregnant women who have insufficient serum levels of vitamin D may have an increased risk of developing preeclampsia, according to findings from the first study of its kind.

If other investigators confirm this association, “preeclampsia may be added to the growing list of nontraditional adverse health effects of vitamin D insufficiency,” Lisa M. Bodnar, Ph.D., said at a conference sponsored by the American Society for Bone and Mineral Research.

Medically indicated preterm deliveries for preeclampsia account for about 15% of all premature births in the United States. Delivery is the only known cure for preeclampsia, and little is known about how to prevent the disorder, said Dr. Bodnar of the department of epidemiology at the University of Pittsburgh.

She and her colleagues conducted a nested case-control study of 49 primigravid women with preeclampsia and 392 women who had normal pregnancy outcomes in the prospective Pregnancy Exposure and Preeclampsia Prevention Study cohort.

The investigators enrolled the patients in the cohort at less than 16 weeks of gestation and obtained samples of maternal blood throughout gestation and cord blood at delivery. Preeclampsia was defined as the new appearance of gestational hypertension and proteinuria after 20 weeks of gestation, and the return of these abnormalities to normal in the postpartum period.

In maternal blood samples that were taken at less than 22 weeks of gestation, women who developed preeclampsia had a significantly lower mean concentration of 25-hydroxy vitamin D (25[OH]D) than did control patients (38.5 nmol/L vs. 42.8 nmol/L). The investigators adjusted the comparison for confounding variables such as race/ethnicity, prenatal multivitamin use, prepregnancy body mass index, and the season.

“In our logistic regression model, we found that vitamin D insufficiency was an important and significant predictor of preeclampsia risk, and that the risk declined as vitamin D status improved to about the nadir of the curves between 80 and 100 nmol/L,” she said.

Compared with a 25(OH)D concentration of 80 nmol/L, the adjusted odds ratio for the risk of preeclampsia declined from 3.5 at 20 nmol/L to 2.7 at 30 nmol/L, 2.1 at 40 nmol/L, and 1.6 at 50 nmol/L; this was a significant trend.

The neonates of preeclamptic mothers had significantly lower mean levels of 25(OH)D in their cord blood at delivery than babies of control women (36.5 nmol/L vs. 43.1 nmol/L). The infants of preeclamptic mothers also were 2.4 times more likely to have a mean 25(OH)D concentration of less than 40 nmol/L than were infants of control patients.

The placenta has vitamin D receptors and expresses 1-α-hydroxylase, which converts stored 25(OH)D into the active compound 1,25(OH)2D. Vitamin D has been shown to regulate the transcription of genes that are important for placental invasion of the uterus and angiogenesis, both of which are critical for normal implantation.

Vitamin D also has ant-inflammatory and immunomodulatory properties, downregulates the blood pressure hormone renin, and is involved in insulin secretion, she said.

The first of two stages that are thought to occur in preeclampsia starts with reduced perfusion of the placenta, which is often secondary to abnormal implantation of the placenta and failed remodeling of maternal blood vessels that supply oxygen and nutrients to the placenta.

The placenta then produces materials that cause oxygen distress, endothelial activation and injury, activation of inflammatory markers, and a reduced perfusion of nearly all organs of the body. The endothelial dysfunction initiates a coagulation cascade and the ensuing second stage of multisystem sequelae, said Dr. Bodnar.

ARLINGTON, VA. — Pregnant women who have insufficient serum levels of vitamin D may have an increased risk of developing preeclampsia, according to findings from the first study of its kind.

If other investigators confirm this association, “preeclampsia may be added to the growing list of nontraditional adverse health effects of vitamin D insufficiency,” Lisa M. Bodnar, Ph.D., said at a conference sponsored by the American Society for Bone and Mineral Research.

Medically indicated preterm deliveries for preeclampsia account for about 15% of all premature births in the United States. Delivery is the only known cure for preeclampsia, and little is known about how to prevent the disorder, said Dr. Bodnar of the department of epidemiology at the University of Pittsburgh.

She and her colleagues conducted a nested case-control study of 49 primigravid women with preeclampsia and 392 women who had normal pregnancy outcomes in the prospective Pregnancy Exposure and Preeclampsia Prevention Study cohort.

The investigators enrolled the patients in the cohort at less than 16 weeks of gestation and obtained samples of maternal blood throughout gestation and cord blood at delivery. Preeclampsia was defined as the new appearance of gestational hypertension and proteinuria after 20 weeks of gestation, and the return of these abnormalities to normal in the postpartum period.

In maternal blood samples that were taken at less than 22 weeks of gestation, women who developed preeclampsia had a significantly lower mean concentration of 25-hydroxy vitamin D (25[OH]D) than did control patients (38.5 nmol/L vs. 42.8 nmol/L). The investigators adjusted the comparison for confounding variables such as race/ethnicity, prenatal multivitamin use, prepregnancy body mass index, and the season.

“In our logistic regression model, we found that vitamin D insufficiency was an important and significant predictor of preeclampsia risk, and that the risk declined as vitamin D status improved to about the nadir of the curves between 80 and 100 nmol/L,” she said.

Compared with a 25(OH)D concentration of 80 nmol/L, the adjusted odds ratio for the risk of preeclampsia declined from 3.5 at 20 nmol/L to 2.7 at 30 nmol/L, 2.1 at 40 nmol/L, and 1.6 at 50 nmol/L; this was a significant trend.

The neonates of preeclamptic mothers had significantly lower mean levels of 25(OH)D in their cord blood at delivery than babies of control women (36.5 nmol/L vs. 43.1 nmol/L). The infants of preeclamptic mothers also were 2.4 times more likely to have a mean 25(OH)D concentration of less than 40 nmol/L than were infants of control patients.

The placenta has vitamin D receptors and expresses 1-α-hydroxylase, which converts stored 25(OH)D into the active compound 1,25(OH)2D. Vitamin D has been shown to regulate the transcription of genes that are important for placental invasion of the uterus and angiogenesis, both of which are critical for normal implantation.

Vitamin D also has ant-inflammatory and immunomodulatory properties, downregulates the blood pressure hormone renin, and is involved in insulin secretion, she said.

The first of two stages that are thought to occur in preeclampsia starts with reduced perfusion of the placenta, which is often secondary to abnormal implantation of the placenta and failed remodeling of maternal blood vessels that supply oxygen and nutrients to the placenta.

The placenta then produces materials that cause oxygen distress, endothelial activation and injury, activation of inflammatory markers, and a reduced perfusion of nearly all organs of the body. The endothelial dysfunction initiates a coagulation cascade and the ensuing second stage of multisystem sequelae, said Dr. Bodnar.

ARLINGTON, VA. — Pregnant women who have insufficient serum levels of vitamin D may have an increased risk of developing preeclampsia, according to findings from the first study of its kind.

If other investigators confirm this association, “preeclampsia may be added to the growing list of nontraditional adverse health effects of vitamin D insufficiency,” Lisa M. Bodnar, Ph.D., said at a conference sponsored by the American Society for Bone and Mineral Research.

Medically indicated preterm deliveries for preeclampsia account for about 15% of all premature births in the United States. Delivery is the only known cure for preeclampsia, and little is known about how to prevent the disorder, said Dr. Bodnar of the department of epidemiology at the University of Pittsburgh.

She and her colleagues conducted a nested case-control study of 49 primigravid women with preeclampsia and 392 women who had normal pregnancy outcomes in the prospective Pregnancy Exposure and Preeclampsia Prevention Study cohort.

The investigators enrolled the patients in the cohort at less than 16 weeks of gestation and obtained samples of maternal blood throughout gestation and cord blood at delivery. Preeclampsia was defined as the new appearance of gestational hypertension and proteinuria after 20 weeks of gestation, and the return of these abnormalities to normal in the postpartum period.

In maternal blood samples that were taken at less than 22 weeks of gestation, women who developed preeclampsia had a significantly lower mean concentration of 25-hydroxy vitamin D (25[OH]D) than did control patients (38.5 nmol/L vs. 42.8 nmol/L). The investigators adjusted the comparison for confounding variables such as race/ethnicity, prenatal multivitamin use, prepregnancy body mass index, and the season.

“In our logistic regression model, we found that vitamin D insufficiency was an important and significant predictor of preeclampsia risk, and that the risk declined as vitamin D status improved to about the nadir of the curves between 80 and 100 nmol/L,” she said.

Compared with a 25(OH)D concentration of 80 nmol/L, the adjusted odds ratio for the risk of preeclampsia declined from 3.5 at 20 nmol/L to 2.7 at 30 nmol/L, 2.1 at 40 nmol/L, and 1.6 at 50 nmol/L; this was a significant trend.

The neonates of preeclamptic mothers had significantly lower mean levels of 25(OH)D in their cord blood at delivery than babies of control women (36.5 nmol/L vs. 43.1 nmol/L). The infants of preeclamptic mothers also were 2.4 times more likely to have a mean 25(OH)D concentration of less than 40 nmol/L than were infants of control patients.

The placenta has vitamin D receptors and expresses 1-α-hydroxylase, which converts stored 25(OH)D into the active compound 1,25(OH)2D. Vitamin D has been shown to regulate the transcription of genes that are important for placental invasion of the uterus and angiogenesis, both of which are critical for normal implantation.

Vitamin D also has ant-inflammatory and immunomodulatory properties, downregulates the blood pressure hormone renin, and is involved in insulin secretion, she said.

The first of two stages that are thought to occur in preeclampsia starts with reduced perfusion of the placenta, which is often secondary to abnormal implantation of the placenta and failed remodeling of maternal blood vessels that supply oxygen and nutrients to the placenta.

The placenta then produces materials that cause oxygen distress, endothelial activation and injury, activation of inflammatory markers, and a reduced perfusion of nearly all organs of the body. The endothelial dysfunction initiates a coagulation cascade and the ensuing second stage of multisystem sequelae, said Dr. Bodnar.

ARLINGTON, VA. — Fish oil capsules and multivitamin tablets that contain 10 mcg of vitamin D₃ provide the same increase in stored levels of the vitamin when taken daily during a 4-week period, Kristin Holvik reported at a conference sponsored by the American Society for Bone and Mineral Research.

Even though many types of vitamin supplements are on the market, little is known about whether the bioavailability of vitamin D₃ (cholecalciferol) differs when it is sequestered in fat-containing capsules as opposed to solid tablets, noted Ms. Holvik, a Ph.D. student at the Institute of General Practice and Community Medicine at the University of Oslo.

In a randomized trial, 55 healthy young adults (34 females and 21 males) received 28 days of supplementation with either fish oil capsules or multivitamin tablets, each of which was taken once daily and contained 10 mcg vitamin D₃ (an amount equivalent to 400 IU).

The participants completed a self-administered questionnaire about diet and sun exposure and had a nonfasting venous blood sample drawn at the beginning and end of the study, which took place in Oslo in late winter 2005, according to Ms. Holvik. She won an ASBMR Young Investigator Award for her research, which she presented during a poster session at the conference.

Serum 25-hydroxyvitamin D levels in individuals who took fish oil capsules increased from an average of 48.5 nmol/L to 80.4 nmol/L at the end of the study.

Multivitamin users had a similar rise in serum 25-hydroxyvitamin D levels from a mean of 40.3 nmol/L to 76.5 nmol/L. On average, the participants were aged about 28 years and had a body mass index of about 24 kg/m

ARLINGTON, VA. — Fish oil capsules and multivitamin tablets that contain 10 mcg of vitamin D₃ provide the same increase in stored levels of the vitamin when taken daily during a 4-week period, Kristin Holvik reported at a conference sponsored by the American Society for Bone and Mineral Research.

Even though many types of vitamin supplements are on the market, little is known about whether the bioavailability of vitamin D₃ (cholecalciferol) differs when it is sequestered in fat-containing capsules as opposed to solid tablets, noted Ms. Holvik, a Ph.D. student at the Institute of General Practice and Community Medicine at the University of Oslo.

In a randomized trial, 55 healthy young adults (34 females and 21 males) received 28 days of supplementation with either fish oil capsules or multivitamin tablets, each of which was taken once daily and contained 10 mcg vitamin D₃ (an amount equivalent to 400 IU).

The participants completed a self-administered questionnaire about diet and sun exposure and had a nonfasting venous blood sample drawn at the beginning and end of the study, which took place in Oslo in late winter 2005, according to Ms. Holvik. She won an ASBMR Young Investigator Award for her research, which she presented during a poster session at the conference.

Serum 25-hydroxyvitamin D levels in individuals who took fish oil capsules increased from an average of 48.5 nmol/L to 80.4 nmol/L at the end of the study.

Multivitamin users had a similar rise in serum 25-hydroxyvitamin D levels from a mean of 40.3 nmol/L to 76.5 nmol/L. On average, the participants were aged about 28 years and had a body mass index of about 24 kg/m

ARLINGTON, VA. — Fish oil capsules and multivitamin tablets that contain 10 mcg of vitamin D₃ provide the same increase in stored levels of the vitamin when taken daily during a 4-week period, Kristin Holvik reported at a conference sponsored by the American Society for Bone and Mineral Research.

Even though many types of vitamin supplements are on the market, little is known about whether the bioavailability of vitamin D₃ (cholecalciferol) differs when it is sequestered in fat-containing capsules as opposed to solid tablets, noted Ms. Holvik, a Ph.D. student at the Institute of General Practice and Community Medicine at the University of Oslo.

In a randomized trial, 55 healthy young adults (34 females and 21 males) received 28 days of supplementation with either fish oil capsules or multivitamin tablets, each of which was taken once daily and contained 10 mcg vitamin D₃ (an amount equivalent to 400 IU).

The participants completed a self-administered questionnaire about diet and sun exposure and had a nonfasting venous blood sample drawn at the beginning and end of the study, which took place in Oslo in late winter 2005, according to Ms. Holvik. She won an ASBMR Young Investigator Award for her research, which she presented during a poster session at the conference.

Serum 25-hydroxyvitamin D levels in individuals who took fish oil capsules increased from an average of 48.5 nmol/L to 80.4 nmol/L at the end of the study.

Multivitamin users had a similar rise in serum 25-hydroxyvitamin D levels from a mean of 40.3 nmol/L to 76.5 nmol/L. On average, the participants were aged about 28 years and had a body mass index of about 24 kg/m