EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, May 16, 2005
Media Advisory: To contact corresponding author Elaine Siegfried, M.D., call Nancy Solomon at 314-977-8017.

CERTAIN ACNE TREATMENT DOES NOT INCREASE SYMPTOMS OF DEPRESSION IN ADOLESCENTS

CHICAGO—Adolescents with moderate to severe acne experienced a reduction rather than an increase in symptoms of depression while taking the medication isotretinoin, according to a study in the May issue of the Archives of Dermatology, one of the JAMA/Archives journals.

"Acne can be a painful and disfiguring disease that leaves some individuals with permanent physical and psychological scars," according to background information in the article. A synthetic vitamin A, isotretinoin, which was approved by the Food and Drug Administration in 1982, is the most effective therapy for acne that is unresponsive to other treatment. However, an increasing number of cases of suicide and depression in patients using isotretinoin has raised concern and brought about new labeling and patient-informed consent involving possible psychiatric side effects.

Christina Y. Chia, M.D., from Saint Louis University Health Sciences Center, St. Louis, and colleagues investigated whether patients with moderate to severe acne treated with isotretinoin experienced an increase in depressive symptoms compared with patients treated with conservative therapy. At the beginning of the study, the researchers assessed 132 patients ages 12 to 19 years for depression using the Center for Epidemiologic Studies Depression Scale (CES-D). Scores of 17 or above were considered suggestive of depression. Fifty-nine patients received isotretinoin and 73 patients were prescribed conservative therapy, which included a topical antibiotic, topical retinoid, and an oral antibiotic. Depression was assessed three to four months after treatment.

The researchers found that patients in the isotretinoin group did not experience an increase in depressive symptoms. At baseline, 14.3 percent of those in the isotretinoin group and 19.2 percent in the conservative therapy group had CES-D scores of 17 or higher. At follow-up, 8.2 percent of patients in the isotretinoin group and 15.4 percent in the conservative therapy group had CES-D scores suggestive of depression. From baseline to follow-up, the rate of new cases of depression was 4.1 percent in the isotretinoin group and 3.8 percent in the conservative therapy group.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, May 16, 2005
Media Advisory: To contact Thomas D. Horn, M.D., call Leslie Taylor at 501-686-8998.

DERMATOLOGISTS USE IMMUNOTHERAPY TO TREAT WARTS

CHICAGO—Injection of skin test antigens (preparations used in skin tests for immunity) into warts appears to stimulate the immune system and successfully treat the injected wart and also helps to treat distant non-injected warts, according to a study in the May issue of the Archives of Dermatology, one of the JAMA/Archives journals.

Warts are unsightly and often tender or painful, causing most patients with warts to seek treatment. Primary treatment usually involves destruction of the wart using one of a number of different techniques, including cutting it out, applying salicylic acid, freezing it with liquid nitrogen and laser vaporization, according to background information provided in the article. Because wart proliferation is controlled by the immune system, various methods have been tried to stimulate an immune response to the human papillomavirus (HPV), the cause of skin warts. Previous studies have shown that injecting a wart with an antigen preparation of mumps, Candida (a cause of yeast infections) or Trichophyton (a cause of fungal infections) clears the wart and other distant and distinct warts. These skin test antigens, although they can not cause or promote infection themselves, cause a reaction on the skin if a person has been previously exposed to mumps, Candida or Trichophyton, and are used to test for immunity.

Thomas D. Horn, M.D., of the University of Arkansas for Medical Sciences, Little Rock, and colleagues conducted a randomized, clinical trial to determine the effectiveness of wart treatment with injection of skin test antigen. Warts were injected with antigen alone, antigen plus interferon alfa-2b (a chemical produced by the immune system), interferon alfa-2b alone or normal saline. Patients who had more than one wart were also tested for an immune response to HPV. Because interferon alfa-2b had no impact on the results, the patient data were analyzed in two groups, those who had received antigen and those who did not.

Of the 201 patients enrolled in the study, 95 received injections of antigen and 106 received injections of either saline or interferon alfa-2b alone. "Fifty-seven subjects injected with antigen were judged to have 100 percent resolution of warts at study conclusion, 21 of whom had more than one wart and experienced 100 percent resolution of all distant warts," the authors report. "In the interferon alfa-2b and saline groups, these numbers were 25 and 11, respectively." The researchers also found that patients who responded to treatment were much more likely to have an immune response to HPV.

"Our repeated observation that untreated warts resolve after injection of only one wart prompts the speculation that intralesional [injection into the wart] immunotherapy induces HPV-directed immunity," the authors write. "Indeed we have observed resolution of hundreds of flat warts in individual patients after injection of only one lesion. ...It is possible that local and distant responses of warts in subjects who received saline or interferon alfa-2b alone develop by the same mechanism as when antigen is injected and that many triggers of an immune response to HPV exist. While injection of saline is an appropriate control, it is not a true placebo. That noted, local and systemic responses to saline injection in this study were far less likely than when antigen was used."

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, May 16, 2005
Media Advisory: To contact corresponding author Gerald D. Weinstein, M.D., call Tom Vasich at 949-824-6455.

HIGH LEVELS OF ESTROGEN DURING PREGNANCY ASSOCIATED WITH IMPROVEMENT IN PSORIASIS

CHICAGO—Increased levels of estrogen that occur during pregnancy may be associated with improvement in psoriasis, according to a study in the May issue of the Archives of Dermatology, one of the JAMA/Archives journals.

Anecdotal reports have suggested that psoriasis tends to improve during pregnancy, according to background information in the article. The current study investigated prospectively how psoriasis fluctuates in pregnancy and correlated progesterone and estrogen levels in pregnancy with psoriatic change.

Jenny E. Murase, M.D., of the University of California, Irvine, and colleagues compared changes over the course of one year in psoriatic body surface area in women with psoriasis in a group of 47 pregnant women and a control group of 27 non-pregnant pre-menopausal women. The women reported on their stress level, perceived psoriatic severity and the extent of their body surface affected by psoriasis five times over the course of the year: pregnant women at 10, 20 and 30 weeks gestation, and six and 24 weeks after birth and the control group at baseline, 10, 20, 36 and 54 weeks following enrollment. Hormone levels at each assessment were determined for 19 of the pregnant women.

During pregnancy, 55 percent of the patients reported improvement in psoriasis, 21 reported no change and 23 percent reported worsening. Only nine percent of patients reported improvement post partum, 26 reported no change and 65 percent reported worsening. Psoriatic body surface area decreased significantly from 10 to 20 weeks' gestation compared to controls and increased significantly six weeks post partum. Although 65 percent of the pregnant patients reported worsening, their psoriatic body surface area only returned to pre-pregnancy levels, the authors report. In pregnant women with 10 percent or greater psoriatic body surface area, lesions decreased by 83.8 percent during pregnancy. Psoriatic body surface area levels in the controls remained the same throughout the year.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, May 16, 2005
Media Advisory: To contact Mary T. Austin, M.D., call Clinton Colmenares at 615-322-4747.

SURVIVAL RATES HIGHER FOR CHILDREN RECEIVING LIVING DONOR LIVER TRANSPLANT

CHICAGO—Children who undergo liver transplantation have better survival rates with living donor liver transplant graft than with deceased donor organ transplant, although factors other than the type of graft also are important, according to a study in the May issue of Archives of Surgery, one of the JAMA/Archives journals.

While the number of children waiting for a liver transplant has doubled since 1993, children under five are the most likely to die while waiting for a liver transplant, according to background information in the article. The need for small-sized grafts coupled with a critical organ shortage have necessitated a turn to alternative sources for children with end-stage liver disease, including living donor liver transplantation (LDLT). In living donor liver transplantation a portion of an adult's healthy liver is transplanted into a child. This is feasible because of the child's smaller size and the ability of the adult liver to regenerate. Although living donor liver transplantation provides a valuable resource for transplantation, the authors note that it also poses some risk to an otherwise healthy donor. Therefore, it is crucial that the transplantation community carefully select candidates for living donor liver transplantation and evaluate the outcomes.

Mary T. Austin, M.D., of Vanderbilt University Medical Center, Nashville, Tenn., and colleagues analyzed data on all pediatric recipients of liver transplants from the United Network for Organ Sharing (UNOS) database from October 1, 1987 to May 24, 2004 to identify variables that would predict graft and patient outcome and to compare the outcomes achieved among the different donor types: deceased donor whole organ transplantations, deceased donor split organ transplantation and living donor liver transplantation.

During that period, 8,771 liver transplantations were performed in the U. S. on children with end-stage liver disease. Of those, 81 percent were deceased donor whole graft, eight percent were deceased donor split graft and 11 percent were living donor grafts. Of the 8,771 liver transplantations, 3,107 failed, with 1778 (57 percent) of these graft failures resulting in transplantation of another donor liver and 1,329 (43 percent) in the child's death. Thirty-seven percent of the deceased donor whole transplantations and 38 percent of deceased donor split transplantations resulted in graft failure compared with 27 percent of the living donor grafts.

The researchers analyzed the patient's pre-transplantation characteristics, including age, cause of liver disease, laboratory data, UNOS urgency status and medical condition, to determine whether the type of graft or differences in the pre-transplantation characteristics of the patients were responsible for the lower graft failure rate of living donor transplantations.

EMBARGOED FOR RELEASE UNTIL 3 P.M. (CT), MONDAY, May 16, 2005
Media Advisory: To contact David J. Ciesla, M.D., call Donna Kettenbach at 303-436-6606.

IMPROVEMENTS IN CRITICAL CARE DECREASE RISK OF POST-INJURY MULTIPLE ORGAN FAILURE

CHICAGO—Improvements in critical care and decreased use of blood transfusions over the course of the last decade are associated with decreases in the rate, severity and risk of death from post-injury multiple organ failure, according to a study in the May issue of the Archives of Surgery, one of the JAMA/Archives journals.

Multiple organ failure (MOF) following injury is a leading cause of in-hospital death and is currently believed to be the result of uncontrolled, systemic inflammation, according to background information in the article. Age of the patient, severity of the injury and receiving a blood transfusion within 12 hours of injury have previously been identified as risk factors. Recent studies have suggested that the incidence and death rate from multiple organ failure has been decreasing due to advances in trauma and critical care.

David J. Ciesla, M.D., of the Denver Health Medical Center, and colleagues analyzed data on severely injured patients admitted to the Rocky Mountain Regional Trauma Center over the course of a 12-year period ending December 31, 2003, to determine whether the incidence and severity of multiple organ failure had decreased over the course of the last decade and to determine whether risk factors for multiple organ failure had changed over the course of the study. Multiple organ failure is based on evaluation of four organ systems, pulmonary, liver, kidney and cardiac. Single organ failure is defined by a dysfunction grade of one or greater on a scale of zero (best) to three (worse). Post-injury multiple organ failure is defined by a total score for the four organ systems of four or more within 48 hours after injury.

Of the 1,244 severely injured patients admitted over the 12-year period, 112 patients (eight percent) died. Of the 339 (25 percent) who developed multiple organ failure, 90 (27 percent) died. Over the course of the study there was a significant increase in the age of patients admitted and the severity of their injuries. At the same time, the number of blood transfusions and proportion of patients receiving more than six units of blood decreased significantly. Blood transfusion was recognized as a consistent early risk factor for multiple organ failure in 1997, prompting a more judicious use of blood transfusions.

After adjusting statistically for all risk factors, the authors were able to determine that there had been a significant decrease in the rate of multiple organ failure; multiple organ failure in 1992 was almost twice the rate observed in 2002. Further, the association between severity of injury and multiple organ failure became less strong in the second half of the study period, suggesting that the effect of injury severity on the development of multiple organ failure decreased over time, the authors report.