Self-Warming Lidocaine/Tetracaine Patch Effectively and Safely Induces Local Anesthesia during Minor Dermatologic Procedures

BACKGROUND Dermatologic procedures often cause some degree of pain. A self-warming patch containing lidocaine and tetracaine (L/T) was developed to provide topical local anesthesia prior to painful procedures.
OBJECTIVES To evaluate the safety and efficacy of a self-warming L/T patch to provide anesthesia in adult patients undergoing minor dermatologic procedures.
METHODS An active or placebo study drug was placed on adults 30 minutes prior to minor dermatologic surgical procedures in a prospectively randomized, double-blinded manner. Subcutaneous lidocaine injection was available during the procedure as a rescue medication if requested by the subject. Immediately following the procedure, the subjects, the investigator, and an independent observer rated pain intensity and adverse events were recorded.
RESULTS Patient-reported pain intensity was significantly lower in the L/T patch group (   p < .001  ). Investigators and an independent observer rated the pain in the L/T patch group to be less than in the placebo patch group (   p = .004  and   p < .001  , respectively). Forty-nine percent of patients in the placebo group required rescue subcutaneous lidocaine compared with 22% in the L/T patch study group (   p = .008  ). One patient in the L/T patch group reported a transient moderate burning sensation.
CONCLUSION The self-warming L/T patch was effective in providing clinically useful local anesthesia for minor dermatologic procedures in adult patients.
ZARS, INC., PROVIDED SUPPORT VIA A SPONSORED RESEARCH GRANT TO THE UNIVERSITY OF MIAMI.     

Gene polymorphisms and serological markers of patients with active Crohn's disease in a clinical trial of antisense to ICAM-1

Serological profiles for anti-Saccharomyces cerevisiae antibodies (ASCA)/ perinuclear antineutrophil cytoplasmic antibodies (pANCA) and gene polymorphisms in tumour necrosis factor (TNF)-alpha and intercellular adhesion molecule-1 (ICAM-1) are associated with occurrence and/or outcome in Crohn's disease. The aim of the study was to characterize the ASCA/pANCA profile, soluble ICAM-1 expression and single nucleotide gene polymorphisms (SNPs) in TNF-alpha and ICAM-1 genes. Crohn's patients with moderate disease activity were enrolled in a clinical trial of Alicaforsen (ISIS 2302). Peripheral blood samples were collected prospectively for serum studies and for potential analysis of gene polymorphisms. A multivariate analysis was performed to compare treatment effect with the biomarkers studied. Serological testing for ASCA/pANCA was obtained for 257 patients at baseline: 37% were ASCA(+)/pANCA(-) (Crohn's pattern), 9% had both markers, 15% were ASCA(-)/pANCA(+) and 39% had neither marker. When the data were analysed by multiple regression analysis, a trend was found within the Alicaforsen-treated groups for greater rates of remission in the ASCA(+)/pANCA(-) subgroup versus all other serological profiles (25 versus 14%, P = 0.068), but not versus the placebo remission rate (18.8%). Gene polymorphisms were assessed in 64 patients, 21 from the placebo group. ICAM-1 assessment revealed no over-representation. However, three unique TNF-alpha SNPs were identified that correlated significantly with remission; sites 290 (P = 0.0253), -2735 (P = 0.0317) and -3090 (P = 0.0067). Although the overall clinical trial was negative, we have identified a trend towards clinical remission with Alicaforsen therapy in a subgroup of patients with Crohn's disease expressing ASCA(+)/pANCA(-). Furthermore, we have identified three TNF-alpha SNPs that may also predict a positive therapeutic outcome.     

Physiologic implications of helium as a carrier gas for inhaled nitric oxide in a neonatal model of Bethanecol-induced bronchoconstriction.

OBJECTIVE: To compare heliox to nitrogen-oxygen (nitrox) as a carrier gas for inducible nitric oxide (iNO) in the presence of pharmacologically inhaled bronchoconstriction. We hypothesized that respiratory resistance and gas exchange would improve when iNO is delivered with heliox. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in the northeastern United States. SUBJECTS: Sedated, ventilated newborn piglets. INTERVENTIONS: Newborn piglets (n = 16; 2.3 +/- 0.1 kg) were placed on a flow-controlled ventilator and given intravenous Bethanecol (2 x 1 mg/kg followed by 1 mg/kg/hr) to induce bronchoconstriction. Piglets were randomized to heliox or nitrox (Fio2 = 0.3) and given 80 ppm iNO. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, blood chemistry, and pulmonary mechanics were recorded at 30-min intervals for 2 hrs. Bethanecol dosing increased inspiratory respiratory resistance (cm H2O/L/min; p < .01) and decreased respiratory compliance (mL/cm H2O/kg; p < .01). Following carrier gas assignment, hemodynamics and respiratory compliance were similar between groups and respiratory resistance decreased (p < .01) in the heliox group. Over 2 hrs with iNO therapy, Paco2 increased (p < .01) whereas blood pH decreased (p < .01) in the heliox group. Respiratory resistance trended downward, oxygenation index improved (p < .01), and blood methemoglobin levels trended higher for nitrox compared with heliox. CONCLUSIONS: The INOvent was effective for controlling heliox delivery of iNO. Despite marked reduction in respiratory resistance with heliox gas ventilation in a neonatal model of pharmacologic bronchoconstriction, nitrox might perform better as a delivery vehicle for iNO.     

Evidence that atrazine and diaminochlorotriazine inhibit the estrogen/progesterone induced surge of luteinizing hormone in female Sprague-Dawley rats without changing estrogen receptor action.

High oral doses of atrazine (ATRA) disrupt normal neuroendocrine function, resulting in suppression of the luteinizing hormone (LH) surge in adult, ovariectomized (OVX) estrogen-primed female rats. While the mechanism by which ATRA inhibits LH secretion is not known, current data indicate that ATRA does have anti-estrogenic properties in vitro and in vivo. In the body, ATRA is rapidly converted to diaminochlorotriazine (DACT). The present study was conducted to investigate the effects of ATRA and DACT on the estradiol benzoate (EB)/progesterone (P) induced LH surge and to determine if such changes correlate with impaired estrogen receptor (ER) function. ATRA, administered by gavage for five consecutive days to adult OVX, female Sprague-Dawley rats, caused a dose-dependent suppression of the EB/P induced LH surge. Although to a lesser degree than ATRA, DACT significantly suppressed total plasma LH and peak LH surge levels in EB/P primed animals by 60 and 58%, respectively. DACT treatment also decreased release of LH from the pituitary in response to exogenous gonadotropin releasing hormone (GnRH) by 47% compared to control. Total plasma LH secretion was reduced by 37% compared to control, suggesting that in addition to potential hypothalamic dysfunction, pituitary function is altered. To further investigate the mechanism by which hypothalamic function might be altered, potential anti-estrogenicity of ATRA and DACT were assessed by evaluating ER function treated rats. Using an in vitro receptor binding assay, ATRA, but not DACT, inhibited binding of [(3)H]-estradiol to ER. In contrast, ATRA, administered to female rats under dosing conditions which suppressed the LH surge, neither changed the levels of unoccupied ER nor altered the estrogen induced up-regulation of progesterone receptor mRNA. Collectively, these results indicate that although ATRA is capable of binding ER in vitro, the suppression of LH after treatment with high doses of ATRA is not due to alterations of hypothalamic ER function.     

Both HCV and HBV are Major Causes of Liver Cancer in Southeast Asians

The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.