Although melanoma accounts for only 4% of skin cancers, it is responsible for 80% of deaths from skin cancers and its incidence in Caucasians has been increasing steadily during the last 30 years. So far, no treatment - except surgery at the earliest stages of the disease - has been shown to significantly improve survival. New treatments are thus clearly needed. The interest of immunologists for melanoma is based on particular features of this tumor. Rare spontaneous regressions have been described, which are possibly mediated by immune responses. Moreover, melanoma cell lines are relatively easy to obtain, providing essential tools for laboratory studies. The first melanoma vaccines involved inoculations of patients with autologous or allogeneic melanoma cells, as well as a variety of immunological adjuvants. Since the beginning of the nineties, the identification of antigens recognized on human tumors by autologous T lymphocytes has opened the way for new vaccination strategies involving molecularly defined tumor antigens. An important group of antigens recognized by T lymphocytes is encoded by “cancer-germ line genes”, which are expressed in tumors of various histological types, but are silent in normal tissues, with the exception of testis germinal cells and placental trophoblast. Since the latter do not express the HLA molecules required to present these antigens to the T lymphocytes, cancer-germ line genes encoded antigens are only present on tumors, which should limit the risk of generating autoimmune diseases as a consequence of vaccination. Therefore, these widely shared tumor specific antigens should represent good targets for the development of cancer vaccines. Our clinical research program of therapeutic vaccinations focuses on antigens encoded by the MAGE family of cancer-germ line genes. Most of the patients included in our phase I/II immunization trials had measurable metastatic melanoma. Several MAGE peptides as well as a recombinant MAGE-3 protein have been tested, while several additional trials are ongoing, including immunizations with a recombinant poxvirus coding for 2 MAGE epitopes. No major toxicity was reported. Tumor regressions have been observed in a minority of patients, mainly those who had regional or distant metastases without visceral involvement. Some of these regressions have been complete and long lasting. Although the rate of objective tumor response observed is low, it is clearly higher than the rate of spontaneous tumor regression observed in melanoma. Other immunization modes against T-cell defined epitopes are currently being explored by several groups in human clinical trials. Vaccines include peptides presented by class I or class II HLA molecules, proteins given alone or mixed with immunological adjuvants or cytokines, recombinant viral or bacterial vectors, dendritic cells and DNA encoding the antigen. Adoptive transfer of T lymphocytes selected for their capacity to recognize defined epitopes presented by the tumor represents another type of approach aiming at the destruction of the tumor by the immune system. It is difficult to predict whether and when therapeutic vaccination against cancer will reach an efficacy that will be sufficient for a standard cancer treatment. Provided their low toxicity, these vaccines should be tested in an adjuvant setting, at earlier stages of the disease.

A viable <i>in vitro</i> excised human skin model was developed to accurately assess cutaneous delivery and metabolism of two ester type compounds; tetracaine (TC) and methyl salicylate (MS). This model could maintain the viability of fresh skin in diffusion cells for 24 hours. Skin viability was assessed using two methods; oxygen consumption measurement and confocal laser scanning microscopy. Two fluorescent probes, calcein AM and ethidium homodimer-1, were used as live and dead markers, respectively. General morphology and localization of nonspecific esterase activity in the skin samples from diffusion cell were checked histologically. Cutaneous delivery and metabolism of MS was evaluated with this viable skin model and compared to human skin homogenate model. A sensitive high performance liquid chromatography (HPLC) assay using reversed phase ion pair was developed/refined to simultaneously analyze TC and its metabolite (4-BABA). Several factors affecting this HPLC system were identified. The limit of detection for TC and 4-BABA was 0.3 ng and 0.5 ng, respectively. The limit of quantitation for TC and 4-BABA was 10 ng and 5 ng, respectively. Linearity was in the range of 10-120 ng for TC and 5-60 ng for 4-BABA. MS was hydrolyzed to salicylic acid (SA) during absorption through fall thickness human breast skin in diffusion cells. The extent of MS hydrolysis was significantly higher in viable skin than in non viable. The extent of absorption of SA through viable and non viable skins was similar. In human skin homogenate, MS was hydrolyzed at the rate of 72.31 nmol/h/[mu]g protein while the hydrolysis in phosphate buffered saline was very low. TC hydrolysis in human skin homogenate was not extensive due to substrate inhibition. From the kinetic study of TC hydrolysis in human skin homogenate, Km was in the 11-28 [mu]M range and Vmax was in the 2.0-2.8 [mu]mol/h/[mu]g protein range. Temperature over 60°C substantially reduced esterase activity in both models therefore caution must be taken during preparation and handling of tissue samples to preserve esterase activity. The viable <i>in vitro</i> excised skin model will provide more accurate quantitation of skin metabolism and absorption of xenobiotics.

The clinicopathological feature of primary cutaneous lymphomas according to WHO/EORTC classification and their relationship to EBV in Taiwan has never been reported. This retrospective study collected the patients with cutaneous lymphomas from 1990 and 2006. The morphology, EBER in situ hybridization and immunohistochemistry of primary cutaneous lymphomas were studied to reclassify based on the WHO/EORTC classification. A total of 54 patients were included. Twenty-nine were primary cutaneous lymphomas and 25 were secondary cutaneous lymphomas. The age ranged from 21 to 86 years old (mean 62 years old). Twenty-one (72.4%) were primary cutaneous T-cell and NK-cell lymphoma, including 5 extranodal NK/T-cell lymphoma, nasal type (17.2%), 5 primary cutaneous peripheral T-cell lymphoma, unspecified (17.2%), 4 mycosis fungoides (13.8%), 1 Sezary syndrome, 3 primary cutaneous anaplastic large cell lymphoma, 2 primary cutaneous small-medium CD4+ T-cell lymphoma and 1 subcutaneous panniculitis-like T-cell lymphoma. Eight cases were primary cutaneous B-cell lymphoma (27.6%) including 3 cutaneous marginal zone B-cell lymphoma (10.3%), 3 cutaneous follicle center B-cell lymphoma (10.3%), and 2 diffuse large B-cell lymphoma, leg type (6.9%). Seventeen cases were secondary cutaneous T-cell and NK -cell lymphoma. Eight cases were secondary cutaneous B-cell lymphoma. All primary and secondary extranodal NK/T-cell lymphoma, nasal type, were positive for EBER, however, one of them (10%) without both angiocentric growth pattern and necrosis in histomorphological examination. This is the first clinicopathological study of cutaneous lymphoma according to recent WHO/EORTC classification in Taiwan. In comparison with the Western countries, mycosis fungoides is less common whereas primary extranodal NK/T-cell lymphoma, nasal type, and peripheral T-cell lymphoma, unspecified, is more common in Taiwan. EBER in situ hybridization study is helpful in the diagnosis of extranodal NK/T-cell lymphoma, nasal type, especially in tumor without both angiocentric growth pattern and necrosis.

Thesis (M.Sc.)--Memorial University of Newfoundland, School of Pharmacy, 1997. / Typescript. Bibliography: leaves 116-141.

Thesis (Ph.D.)--Flinders University, Faculty of Medicine, Dept. of Human Physiology. / Typescript bound. Includes bibliographical references: (leaves 332-374) Also available online via the Web.

Thesis (M.S.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains vii, 70 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 69-70).

The research to date, of transcutaneous electric nerve stimulation on cutaneous blood flow, is equivocal. The purpose of this report is to review the TENS body of knowledge, in particular synthesizing the literature on acupuncture stimulation of cutaneous blood flow with the two fold goal of creating a protocol to increase skin blood flow through the exogenous application of electrical stimulation, as well as creating an engaging engineering challenge for high school anatomy and physiology students. The hypothesis developed was TENS stimulation with electrode placement on specific acupuncture points would influence cutaneous blood flow as measured using laser Doppler flowmetry. The findings of this project did not support the hypothesis of TENS or Interferential electrical stimulation, in combination with acupuncture points or not, influencing skin blood flow. Perhaps this is due to the physiological differences between glabrous and non-glabrous skin and the different electrical resistances of each dermal layer, nerve stimulation, age and gender of subject or some combination thereof. These equivocal findings may also be the result of inconsistencies in testing protocols, such as subject preconditioning or not, subject’s position during administration of stimulation, electrode size and placement to name a few. Ultimately, this report provides a summary of the research to date, as well as outlining how this research could be adapted to supply engaging bio engineering challenges in the classroom including challenges to develop a model for delivering current to muscle; develop a model for skin blood flow management to name a few. / text

Although Tianjiu Therapy in Sanfu Days (三伏天灸) is extensively being used for the treatment of asthma in Mainland China, there is a lack of convincing evidence to support its efficacy to expand its clinical application into asthma treatment. This study incorporated two related studies, the first was a randomized, double-blind, placebo-controlled trial with an aim to evaluate the efficacy of Tianjiu Therapy in Sanfu Days for patients suffering from chronic asthma. The second was a self-control clinical efficacy observation study aiming to compare the efficacy of 2 courses Tianjiu Therapy with 1 course such treatment in order to find the optimal duration of Tianjiu Therapy. In the first study, 323 patients with chronic asthma were randomly assigned to Tianjiu Therapy group (n=165), and placebo group (n=158). There was no significant difference in primary and secondary outcome as compared with placebo group at the end of 3rd treatment and four times follow ups. But sub-analysis of secondary outcome in four times follow ups showed that Tianjiu Therapy significantly reduced the proportion of participants who didn’t need medical treatment during asthma attack increased from 6% to 15% at 1st follow up and 0% to 7% at 3rd follow up (P<0.05). In addition, Tianjiu Therapy was significantly superior to placebo in reducing the percentage of participants who were susceptibly waken up by asthma symptoms from 27% to 14%, and the percentage of participants who had the symptom of running nose and sneezing before onset from 18% to 8% at 2nd follow up ( P<0.05). Improvements also occurred with treatment group, it reduced the proportion of participants who were spontaneous sweating at 3rd follow up (P<0.05). In the second study, totally 102 patients received two courses of Tianjiu Therapy (3 sessions Tianjiu Therapy in a year constituted one course of treatment). After treatment, the number of symptoms which were associated with Chinese Medicine added by 1.38 points (95% CI, 0.25 to 2.51), 2.93±0.41 in the 1 course group and 4.31±0.41 in the 2 courses group (P<0.05). The number of days with asthma-related symptoms increased by 3.05 points (95% CI, 0.37 to 5.73), 1.98±0.96 in 1 course group and 5.03±0.96 in 2 courses group (P<0.05). But both 1 course and 2 courses Tianjiu Therapy as compared with baseline (didn’t receive Tianjiu Therapy at this time point) have a significant improvement in the most outcome measurements. From study 1, it was found that Tianjiu Therapy significantly decreased the need for pharmaceuticals to control asthma and improved the quality of participants’ life after one course Tianjiu Therapy. Study 2 indicated that although 2 courses Tianjiu Therapy was not as effective as 1 course Tianjiu Therapy in the treatment of asthma, both 1 course and 2 courses Tianjiu Therapy provided a significant improvement as compared with baseline. It was still unknown the optimal duration of Tianjiu Therapy, so it was worth to conduct the third course or more Sanfutianjiu Thearpy in future. / published_or_final_version / Chinese Medicine / Master / Master of Philosophy

Methods for assessing small peripheral nerve fiber function objectively are limited. The cutaneous silent period (CuSP), a transient supression of electromyographic voluntary activity that follows painful stimuli, could serve as an objective functional measure of the A delta fibers. The aim of this study was to evaluate function of small diameter A delta nerve fibers using the CuSP in normals and in patients with both focal (carpal tunnel syndrome - CTS) and generalised (polyneuropathies - PNP) peripheral nerve injuries. The objectives of the study were the following: 1. To determine the CuSP normal values by age, gender, side, height and weight in healthy controls. 2. To study the topography and extension of the CuSP by changing recording and stimulating sites in healthy controls. 3. To evaluate the CuSP in patients with CTS of different severity and to compare these results with those of healthy controls. 4. To estimate the CuSP onset latency and duration in relation with median nerve evoked compound muscle action potential amplitude, distal latency and conduction velocity in patients with CTS. 5. To evaluate the CuSP in patients with PNP of different types and to compare these results with those of healthy controls. 6. To estimate the CuSP onset latency and duration in relation with median nerve evoked compound muscle action potential amplitude, distal latency and conduction velocity in patients with PNP. We investigated the CuSP of the upper and lower limbs of 50 normal... [to full text]

In the healthy young, stimulation of superficial peroneal nerve (SPn) cutaneous afferents at the ankle during walking has been shown to elicit functionally relevant neural and mechanical responses that contribute to obstacle avoidance during swing and have been referred to as stumble corrective responses. However, specific age-related differences in the stumble corrective response induced by electrically evoked cutaneous stimulation have yet to be determined. As a confounding contributor to age related changes in dynamic stability during locomotion, neural and mechanical changes in the stumble corrective response may result in a decreased ability to recover from a destabilizing incident and provide key markers of neuromuscular decline. Therefore the purpose of this study was to compare age-dependent differences in responses to electrically evoked stimulation of the superficial peroneal nerve at the ankle during walking in healthy young and elderly groups. Electromyograms (EMG) of the tibialis anterior (TA), soleus (Sol), medial gastrocnemius (MG), biceps femoris (BF) and vastus lateralis (VL) were recorded along with gait kinematics including joint displacement and angular velocity at the ankle and knee as well as toe clearance relative to the walking surface. Overall, the stumble corrective response was preserved in the elderly as evident by significant responses in kinematics and muscle activity that were similar in sign and phase to those seen in the healthy young. However, the magnitude of the kinematic responses and resulting toe clearance in older adults were significantly smaller than in the young. Further, during the swing phase of unstimulated walking cycles, there were reduced knee flexion, plantarflexion and toe clearance in the elderly with corresponding differences in muscle activity. Therefore, smaller kinematic responses to stimulation, in the elderly, superimposed on a different undisturbed gait profile, resulting in reduced toe clearance, reflects early degradation of the stumble corrective response. This early degradation is likely a prodromal sign of increased fall risk. This supports the potential use of cutaneous reflexes in quantifying degradation of neuromuscular control and its contribution to fall risk. / Graduate / 0317 / 0758 / rbrodie@uvic.ca