Visual scoring and laser Doppler perfusion imaging of skin irritancy induced by different nicotine patches

Background/aims: Local skin reactions are the most common reason for discontinuation of transdermal nicotine replacement therapy in smoking cessation programs. The aims of the present study were (1) to quantify the intensity of skin reactions induced by different types of nicotine patches and (2) to compare the clinical evaluation of skin erythema using visual scores with independently performed quantitative estimates of skin perfusion.
Methods: Thirty-three subjects were included in the study, each receiving 2 different types of nicotine patches (Nicotinell and Nicorette) and 1 type of placebo patch (Nicorette), placed ventrally on the upper arms according to a randomized protocol. Patches were removed after 24 h (Nicotinell) and 16 h (Nicorette), respectively, according to recommended application times. Visual scoring and laser Doppler perfusion imaging were performed 45 min after removal of patches, in a randomized order.
Results: Nicotinell patches induced the highest cumulative clinical score for skin irritancy. All 3 investigated patches gave rise to a slight but significant skin perfusion increase and individual visual scores and perfusion data correlated.
Conclusion The degree of skin irritancy and underlying perfusion increase induced by 1 daily maintenance dose of transdermal nicotine via a patch is low, but differs between patch types.     

Ethinyl estradiol treats collagen-induced arthritis in DBA/1LacJ mice by inhibiting the production of TNF-alpha and IL-1beta

We previously demonstrated the therapeutic effects of ethinyl estradiol (EE), an orally active estrogen and a component of birth control pills, in encephalitogenic autoimmune encephalomyelitis (EAE). In this study, we report the effectiveness of EE in treating collagen-induced arthritis (CIA) induced with bovine type II collagen (bCII) in DBA/1LacJ mice, a CIA susceptible strain. Both low and high doses of EE notably suppressed clinical and histological signs of CIA in a dose-dependent manner compared to vehicle-treated controls. Oral treatment with EE decreased proliferation and secretion of pro-inflammatory factors, TNF-alpha IFN-gamma, MCP-1 and IL-6 by bCII peptide-specific T cells, production of bCII-specific IgG2a antibodies, and mRNA for cytokines, chemokines and chemokine receptors in joint tissue. This is the first report demonstrating effective treatment of joint inflammation and clinical signs of CIA with orally administered ethinyl estradiol, thus supporting its possible clinical use for treating rheumatoid arthritis in humans.     

Immunological response to highly active antiretroviral therapy in children with clinically stable HIV-1 infection

We studied changes in 60 immunological parameters after the administration of highly active antiretroviral therapy (HAART) in 192 clinically stable antiretroviral drug-experienced HIV-1-infected children 4 months-17 years old. The studied immunological parameters included standard lymphocyte subsets and lymphocyte surface markers of maturation and activation. The most significant changes during the 48-week study period were seen for CD8(+), CD8(+)CD62L(+)CD45RA(+), CD8(+)CD38(+)HLA-DR(+), and CD4(+) T cell percentages (P < .0001 for all parameters). These changes suggest that significant decreases in the expression of activation markers and increases in the expression of naive markers in the CD8(+) T cell population may be related to better virologic control in these HIV-1-infected children, who had relatively stable immune function at the initiation of HAART. At week 44 of HAART, the major immunological parameters in these HIV-1-infected children moved from baseline values to about halfway to two-thirds of the way toward the values in healthy, uninfected children.     

Functional analysis of HIV type 1 Nef gene variants from adolescent and adult survivors of perinatal infection

Throughout the world, infants and children with HIV-1 infection are increasingly surviving into adolescence and adulthood. As HIV Nef is an important determinant of the pathogenic potential of the virus, we examined nef alleles in a cohort of extreme long-term survivors of HIV infection (average age of 16.6 years) to determine if Nef defects might have contributed to patient survival. HIV nef gene sequences were amplified for phylogenetic analysis from 15 adolescents and adults infected by mother-to-child transmission (n=10) or by blood transfusion (n=5). Functional analysis was performed by inserting patient-derived nef sequences into an HIV-derived vector that permits simultaneous evaluation of the impact of the Nef protein on MHC-I and CD4 cell surface expression. We found evidence of extensive nef gene diversity, including changes in known functional domains involved in the downregulation of cell surface MHC-I and CD4. Only 3 of 15 individuals (20%) had nef alleles with a loss of the ability to downregulate either CD4 or MHC-I. Survival into adulthood with HIV infection acquired in infancy is not uniformly linked to loss of function in nef. The Nef protein remains a potential target for immunization or pharmacologic intervention.     

Cephalometric analysis in patients with obstructive sleep apnoea syndrome: II. Soft tissue morphology

Oropharyngeal soft tissue profiles were studied by cephalometric analysis in 25 patients with obstructive sleep apnoea syndrome (OSAS) and 10 controls. The length of the soft palate was significantly higher in patients (48.0 +/- 4.3 mm. (mean +/- SD) than in controls (35.3 +/- 4.6 mm.) (p less than 0.001), as was the distance of close contact between the tongue and the soft palate (23 +/- 12 mm. and 10 +/- 8 mm., respectively) (p less than 0.01). The area of the soft palate, measured in the sagittal plane, was 4.85 +/- 0.80 cm.2 and 2.88 +/- 0.62 in the patient and the control group, occupying 39 +/- 8 per cent and 21 +/- 5 per cent of the pharyngeal area (p less than 0.001). The lower outline of the tongue, represented by the line between vallecula (V) and the hyoid bone (AH) was more inferiorly positioned in patients, apparently giving the tongue a more upright position with more of the tongue tissue at the hypopharyngeal level than found in normals. The pharyngeal airway space had significantly reduced anteroposterior dimensions both at the nasopharyngeal and velopharyngeal level (P less than 0.001) as well as the hypopharyngeal level (p less than 0.05). Cephalometric analysis is highly recommended as a valuable tool in the presurgical evaluation of OSAS patients.