Epinephrine autoinjector refill history in an HMO.

Epinephrine can be lifesaving in episodes of anaphylaxis, yet it is underprescribed and underused. Tracking of epinephrine refills over time for patients with a diagnosis of anaphylaxis has not been reported. This study reports on the refill history of 14,677 patients in a large HMO who received an initial dispensing of EpiPen (Dey Pharma, Basking Ridge, NJ) or EpiPen Jr between 2000 and 2006. A total of 6,776 (46%) refilled at least once. Twenty-five percent of the patients who were in the cohort for 5 years or more refilled multiple times, and 11% refilled consistently at all expected refill times. Infants through children 12 years of age were more likely to receive a refill dispensing (63%) compared with teenagers and adults (40%). The most common ICD-9 codes that were linked to the initial epinephrine dispensing were allergic disorder (37%), miscellaneous anaphylaxis/angioedema (23%), hymenoptera/insect bite or sting (14%), and specific or nonspecific food allergy (11%). A total of 79% of patients with a food-related ICD-9 code and 59% of patients with an insect sting-related ICD-9 code refilled epinephrine at least once. An opportunity exists to identify system-based as well as personal barriers in an ongoing effort to provide patients at risk with the tools and empowerment that could reduce their risk during life-threatening anaphylactic reactions.

Binding of upstream stimulatory factor 1 to the E-box regulates the 4G/5G polymorphism-dependent plasminogen activator inhibitor 1 expression in mast cells.

BACKGROUND: Plasminogen activator inhibitor (PAI)-1 is a key regulator of the fibrinolytic system. PAI-1 levels are markedly elevated in the asthmatic airways. The 4G/5G polymorphism of the PAI-1 gene is associated with allergic asthma. OBJECTIVE: To characterize the mechanisms of the 4G/5G-dependent PAI-1 expression in mast cells (MCs), a major source of PAI-1 and key effector cells in asthma. METHODS: Transcription of PAI-1 was assessed by transiently transfecting human MC line (HMC-1) cells with the luciferase-tagged PAI-1 promoters containing the 4G or 5G allele (4G-PAI-1 or 5G-PAI-1 promoter). Upstream stimulatory factor (USF)-1 and the E-box interactions were studied by electrophoretic mobility shift assays and supershift assays. Expression of USF-1 was determined by Western blot analysis. RESULTS: The 4G-PAI-1 promoter has higher promoter activity than the 5G-PAI-1 promoter in stimulated HMC-1 cells, and the E-box adjacent to the 4G/5G site (E-4G/5G) regulates the genotype-specific PAI-1 transcription. USF-1 binds to the E-4G with greater affinity than to the E-5G. USF-1 level is increased in HMC-1 cells after stimulation, and elevated USF-1 enhances PAI-1 transcription. Overexpression of wild-type USF-1 or dominant-negative USF remedies the 4G/5G-dependent PAI-1 transcription. CONCLUSION: Binding of USF-1 to the E-4G/5G regulates the 4G/5G polymorphism-dependent PAI-1 expression in MCs.

Increasing incidence of lentigo maligna melanoma subtypes: northern California and national trends 1990-2000.

Worldwide, lentigo maligna melanoma (LMM) comprises 4%-15% of cutaneous melanoma and occurs less commonly than superficial spreading or nodular subtypes. We assessed the incidence of melanoma subtypes in regional and national Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1990 to 2000. Because 30%-50% of SEER data were not classified by histogenetic type, we compared the observed SEER trends with an age-matched population of 1024 cases from Stanford University Medical Center (SUMC) (1995-2000). SEER data revealed lentigo maligna (LM) as the most prevalent in situ subtype (79%-83%), and that LMM has been increasing at a higher rate compared with other subtypes and to all invasive melanoma combined for patients aged 45-64 and > or =65 y. The SUMC data demonstrated LM and LMM as the only subtypes increasing in incidence over the study period. In both groups, LM comprised > or =75% of in situ melanoma and LMM > or =27% of invasive melanoma in men 65 y and older. Regional and national SEER data suggest an increasing incidence of LM and LMM, particularly in men > or =age 65. An increased incidence of LM subtypes should direct melanoma screening to heavily sun-exposed sites, where these subtypes predominate.