Capecitabine in the treatment of metastatic renal cell carcinoma

To evaluate the therapeutic effects and systemic toxicities of a capecitabine-based home therapy regimen in patients with metastatic renal cell carcinoma, 30 patients were enrolled in a phase II clinical trial. Treatment consisted of oral capecitabine combined with subcutaneous recombinant human interferon-α 2a, recombinant human interleukin-2 and oral 13-cis-retinoic acid. There were two (7%) complete responses (CRs) and eight (27%) partial remissions (PRs), for an overall objective response rate of 34% (95% CI 17–53%). Except one, all responses are ongoing, with a median duration of 9+ and 8+ months for CRs and PRs, respectively. Additionally, 12 patients (40%) reached stable disease. Eight patients (27%) showed continued disease progression despite treatment. Therapy was well tolerated and was given in the outpatient setting. Capecitabine-related World Health Organization (WHO) grade 2 and 3 toxicities were observed in five and two patients respectively, and were limited to fatigue, nausea/vomiting, diarrhoea, stomatitis, dermatitis and hand-and-foot syndrome. The substitution of capecitabine for 5-FU in the pre-existing biochemotherapy regimen did not result in a reduced therapeutic efficacy and showed significant anti-tumour activity in patients with advanced renal cell carcinoma. © 2000 Cancer Research Campaig

Hair follicles as a target structure for nanoparticles

For at least two decades, nanoparticles have been investigated for their capability to deliver topically applied substances through the skin barrier. Based on findings that nanoparticles are highly suitable for penetrating the blood–brain barrier, their use for drug delivery through the skin has become a topic of intense research. In spite of the research efforts by academia and industry, a commercial product permitting the nanoparticle-assisted delivery of topically applied drugs has not yet been developed. However, nanoparticles of approximately 600 nm in diameter have been shown to penetrate efficiently into the hair follicles, where they can be stored for several days. The successful loading of nanoparticles with drugs and their triggered release inside the hair follicle may present an ideal method for localized drug delivery. Depending on the particle size, such a method would permit targeting specific structures in the hair follicles such as stem cells or immune cells or blood vessels found in the vicinity of the hair follicles

Increased fibrosis in a mouse model of anti-laminin 332 mucous membrane pemphigoid remains unaltered by inhibition of aldehyde dehydrogenase

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies against the basal membrane zone of skin and surface-close epithelia and predominant mucosal lesions. The oral cavity and conjunctivae are most frequently affected, albeit clinical manifestations can also occur on the skin. MMP-associated lesions outside the oral cavity typically lead to scarring. Mechanisms underlying scarring are largely unknown in MMP and effective treatment options are limited. Herein, we assessed the collagen architecture in tissue samples of an antibody-transfer mouse model of anti-laminin-332 MMP. In MMP mice, increased collagen fibril density was observed in skin and conjunctival lesions compared to mice injected with normal rabbit IgG. The extracellular matrix of MMP skin samples also showed altered post-translational collagen cross-linking with increased levels of both lysine- and hydroxylysine-derived collagen crosslinks supporting the fibrotic phenotype in experimental MMP compared to control animals. In addition, we evaluated a potential anti-fibrotic therapy in experimental anti-laminin-332 MMP using disulfiram, an inhibitor of the aldehyde dehydrogenase (ALDH), which has been implicated in immune-mediated mucosal scarring. In addition, disulfiram also acts as a copper chelator that was shown to block lysyl oxidase activity, an enzyme involved in formation of collagen crosslinks. Topical use of disulfiram (300 μM in 2 [w/v] methocel) did not improve ocular lesions in experimental MMP over the 12-day treatment period in disulfiram-treated mice compared to vehicle-treated mice (n=8/group). Furthermore, C57BL6/J mice (n=8/group) were treated prophylactically with 200 mg/kg p.o. disulfiram or the solvent once daily over a period of 12 days. Systemic treatment did not show any reduction in the severity of oral and ocular lesions in MMP mice, albeit some improvement in skin lesions was observed in disulfiram- vs. vehicle-treated mice (p=0.052). No reduction in fibrosis was seen, as assessed by immunohistochemistry. Whilst blocking of ALDH failed to significantly ameliorate disease activity, our data provide new insight into fibrotic processes highlighting changes in the collagenous matrix and cross-linking patterns in IgG-mediated MMP

Skin Disinfection by Plasma-Tissue Interaction: Comparison of the Effectivity of Tissue-Tolerable Plasma and a Standard Antiseptic

Wound healing disorders frequently occur due to biofilm formation on wound surfaces requiring conscientious wound hygiene. Often, the application of conventional liquid antiseptics is not sufficient and sustainable as (1) the borders and the surrounding of chronic wounds frequently consist of sclerotic skin, impeding an effectual penetration of these products, and (2) the hair follicles representing the reservoir for bacterial recolonization of skin surfaces are not affected. Recently, it has been reported that tissue-tolerable plasma (TTP), which is used at a temperature range between 35 and 45°C, likewise has disinfecting properties. In the present study, the effectivity of TTP and a standard liquid antiseptic was compared in vitro on porcine skin. The results revealed that TTP was able to reduce the bacterial load by 94%, although the application of the liquid antiseptic remained superior as it reduced the bacteria by almost 99%. For in vivo application, however, TTP offers several advantages. On the one hand, TTP enables the treatment of sclerotic skin as well, and on the other hand, a sustainable disinfection can be realized as, obviously, also the follicular reservoir is affected by TTP

A rehabilitation program for lung cancer patients during postthoracotomy chemotherapy

Objective: The objective of this pilot study was to describe the effects of a 16-week home-based rehabilitative exercise program on cancer-related fatigue (CRF), other symptoms, functional status, and quality of life (QOL) for patients with non-small cell lung cancer (NSCLC) after thoracotomy starting within days after hospital discharge and continuing through the initiation and completion of chemotherapy. Materials and methods: Five patients with NSCLC completed the Brief Fatigue Inventory (measuring CRF severity) and the MD Anderson Symptom Inventory (measuring symptom severity) before and after thoractomy, and at the end of each week of the 16-week exercise program. Additionally, the Medical Outcomes Study Short Form-36 (measuring physical and mental functional status) and the Quality of Life Index (measuring QOL) were completed before and after thoracotomy, after weeks 3, 6, 12, and 16 (the end of the exercise program). Further, the 6-minute walk test (measuring functional capacity) was administered before thoracotomy, prior to the initiation of chemotherapy and/or radiation therapy, and at the end of the 16-week exercise program, after completion of chemotherapy. Results: Participants had a mean age of 63 years and a mean of five comorbid conditions; the exercise program was initiated within 4 days after hospital discharge. Participants\u27 CRF severity scores were reduced to mild levels, while the mean number of symptoms decreased from 9 postthoracotomy to 6 after the exercise program, with mean levels of severity and interference decreasing to below prethoracotomy levels. Likewise, participants\u27 functional status and QOL after completing the exercise program improved to near or above prethoracotomy levels. Conclusion: The home-based, light-intensity exercise program for NSCLC patients receiving and completing adjuvant chemotherapy postthoracotomy showed promising trends in improving CRF severity, other symptom severity, functional status, and QOL. Further testing via a two-arm randomized controlled trial is being conducted

Comparison of the Antiseptic Efficacy of Tissue-Tolerable Plasma and an Octenidine Hydrochloride-Based Wound Antiseptic on Human Skin

Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area

Possible Cosmological Implications of the Quark-Hadron Phase Transition

We study the quark-hadron phase transition within an effective model of QCD, and find that in a reasonable range of the main parameters of the model, bodies with quark content between $10^{-2}$ and 10 solar masses can have been formed in the early universe. In addition, we show that a significant amount of entropy is released during the transition. This may imply the existence of a higher baryon number density than what is usually expected at temperatures above the QCD scale. The cosmological QCD transition may then provide a natural way for decreasing the high baryon asymmetry created by an Affleck-Dine like mechanism down to the value required by primordial nucleosynthesis.Comment: 19 pages, LaTeX, 5 Postscript figures included. Submitted to Journal of Physics