Determination of the Maximum Rate of Eccrine Sweat Glands’ Ion Reabsorption Using the Galvanic Skin Conductance to Local Sweat Rate Relationship

Purpose The purpose of the present study was to develop and describe a simple method to evaluate the rate of ion reabsorption of eccrine sweat glands in human using the measurement of galvanic skin conductance (GSC) and local sweating rate (SR). This purpose was investigated by comparing the SR threshold for increasing GSC with following two criteria of sweat ion reabsorption in earlier studies such as 1) the SR threshold for increasing sweat ion was at approximately 0.2 to 0.5 mg/cm2/min and 2) exercise-heat acclimation improved the sweat ion reabsorption ability and would increase the criteria 1. Methods Seven healthy non-heat-acclimated male subjects received passive heat treatment both before and after 7 days of cycling in hot conditions (50% maximum oxygen uptake, 60 min/day, ambient temperature 32°C, and 50% relative humidity). Results Subjects became partially heat-acclimated, as evidenced by the decreased end-exercise heart rate (p<0.01), rate of perceived exhaustion (p<0.01), and oesophageal temperature (p=0.07), without alterations in whole-body sweat loss, from the first to the last day of training. As hypothesised, we confirmed that the SR threshold for increasing GSC was near the predicted SR during passive heating before exercise heat acclimation, and increased significantly after training (0.19 ± 0.09 to 0.32 ± 0.10 mg/cm2/min, p<0.05). Conclusions The reproducibility of sweat ion reabsorption by the eccrine glands in the present study suggests that the relationship between GSC and SR can serve as a new index for assessing the maximum rate of sweat ion reabsorption of eccrine sweat glands in humans.

Fractional order inductive phenomena based on the skin effect

The Maxwell equations play a fundamental role in the electromagnetic theory and lead to models useful in physics and engineering. This formalism involves integer-order differential calculus, but the electromagnetic diffusion points towards the adoption of a fractional calculus approach. This study addresses the skin effect and develops a new method for implementing fractional-order inductive elements. Two genetic algorithms are adopted, one for the system numerical evaluation and another for the parameter identification, both with good results.

Predictive Variables Affecting Transfusion Requirements in Orthotopic Liver Transplantation

INTRODUCTION AND AIMS: Adult orthotopic liver transplantation (OLT) is associated with considerable blood product requirements. The aim of this study was to assess the ability of preoperative information to predict intraoperative red blood cell (RBC) transfusion requirements among adult liver recipients. METHODS: Preoperative variables with previously demonstrated relationships to intraoperative RBC transfusion were identified from the literature: sex, age, pathology, prothrombin time (PT), factor V, hemoglobin (Hb), and platelet count (plt). These variables were then retrospectively collected from 758 consecutive adult patients undergoing OLT from 1997 to 2007. Relationships between these variables and intraoperative blood transfusion requirements were examined by both univariate analysis and multiple linear regression analysis. RESULTS: Univariate analysis confirmed significant associations between RBC transfusion and PT, factor V, Hb, Plt, pathology, and age (P values all < .001). However, stepwise backward multivariate analysis excluded variables Plt and factor V from the multiple regression linear model. The variables included in the final predictive model were PT, Hb, age, and pathology. Patients suffering from liver carcinoma required more blood products than those suffering from other pathologies. Yet, the overall predictive power of the final model was limited (R(2) = .308; adjusted R(2) = .30). CONCLUSION: Preoperative variables have limited predictive power for intraoperative RBC transfusion requirements even when significant statistical associations exist, identifying only a small portion of the observed total transfusion variability. Preoperative PT, Hb, age, and liver pathology seem to be the most significant predictive factors but other factors like severity of liver disease, surgical technique, medical experience in liver transplantation, and other noncontrollable human variables may play important roles to determine the final transfusion requirements.

Liver Depurative Techniques: A Single Liver Transplantation Center Experience

In a liver transplant (LT) center, treatments with Prometheus were evaluated. The main outcome considered was 1 and 6 months survival. Methods. During the study period, 74 patients underwent treatment with Prometheus; 64 were enrolled,with a mean age of 51 13 years; 47men underwent 212 treatments (mean, 3.02 per patient). The parameters evaluated were age, sex, laboratorial (liver enzymes, ammonia) and clinical (model for end-stage liver disease and Child-Turcotte-Pugh score) data. Results. Death was verified in 23 patients (35.9%) during the hospitalization period, 20 patients (31.3%) were submitted to liver transplantation, and 21 were discharged. LT was performed in 4 patients with acute liver failure (ALF, 23.7%), in 7 patients with acute on chronic liver failure (AoCLF, 43.7%), and in 6 patients with liver disease after LT (30%). Seven patients who underwent LT died (35%). In the multivariate analysis, older age (P ¼ .015), higher international normalized ratio (INR) (P ¼ .019), and acute liver failure (P ¼ .039) were independently associated with an adverse 1-month clinical outcome. On the other hand, older age (P ¼ .011) and acute kidney injury (P ¼ .031) at presentation were both related to worse 6-month outcome. For patients with ALF and AoCLF we did not observe the same differences. Conclusions. In this cohort, older age was the most important parameter defining 1- and 6-month survival, although higher INR and presence of ALF were important for 1-month survival and AKI for 6-month survival. No difference was observed between patients who underwent LT or did not have LT.

Infections After Liver Transplantation: A Retrospective, Single-Center Study

Objective. To access the incidence of infectious problems after liver transplantation (LT). Design. A retrospective, single-center study. Materials and Methods. Patients undergoing LT from January 2008 to December 2011 were considered. Exclusion criterion was death occurring in the first 48 hours after LT. We determined the site of infection and the bacterial isolates and collected and compared recipient’s variables, graft variables, surgical data, post-LT clinical data. Results. Of the 492 patients who underwent LT and the 463 considered for this study, 190 (Group 1, 41%) developed at least 1 infection, with 298 infections detected. Of these, 189 microorganisms were isolated, 81 (51%) gram-positive bacteria (most frequently Staphylococcus spp). Biliary infections were more frequent (mean time of 160.4 167.7 days after LT); from 3 months after LT, gram-negative bacteria were observed (57%). Patients with infections after LT presented lower aminotransferase levels, but higher requirements in blood transfusions, intraoperative vasopressors, hemodialysis, and hospital stay. Operative and cold ischemia times were similar. Conclusion. We found a 41% incidence of all infections in a 2-year follow-up after LT. Gram-positive bacteria were more frequent isolated; however, negative bacteria were commonly isolated later. Clinical data after LT were more relevant for the development of infections. Donors’ variables should be considered in future analyses.

Long-Term Recurrence of Nonmelanoma Skin Cancer after Topical Methylaminolevulinate Photodynamic Therapy in a Dermato-Oncology Department

BACKGROUND: Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE: To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS: The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS: A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS: Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.

Desensitization of thermal hyperemia in the skin is reproducible.

OBJECTIVE: Local heating increases skin blood flow SkBF (thermal hyperemia). In a previous study, we reported that a first local thermal stimulus could attenuate the hyperemic response to a second one applied later on the same skin spot, a phenomenon that we termed desensitization. However, other studies found no evidence for desensitization in similar conditions. The aim of the present work was to test whether it was related to differences in instrumentation. METHODS: Twenty-eight healthy young males were studied. Two pairs of heating chambers, one custom-made (our study) and one commercial (other groups), were affixed to forearm skin. SkBF was measured with single-point laser-Doppler flowmetry (LDF) (780nm) in one pair, and laser-Doppler imaging (LDI) (633nm) in the other. A temperature step from 34 to 41°C, was applied for 30minutes and repeated after two hours. RESULTS: During the second thermal challenge, the plateau SkBF was lower than during the first thermal and was observed with each of the four combinations of SkBF measurement techniques and heating equipment (p<0.05 for all conditions, range -9% to -16% of the initial value). CONCLUSION: Desensitization of thermal hyperemia is not specific to peculiar operating conditions.

Stem Cell Transplantation for Retinal Degenerations

Within the last few years, several reports have revealed that cell transplantation can be an effective way to replace lost neurons in the central nervous system (CNS) of patients affected with neurodegenerative diseases. Concerning the retina, the concept that newborn photoreceptors can integrate the retina and restore some visual functions was univocally demonstrated recently in the mouse eye (MacLaren et al. 2006) and remains to be achieved in human. These results pave the way to a standard approach in regenerative medicine aiming to replace lost photoreceptors. With the discovery of stem cells a great hope has appeared towards elaborating protocols to generate adequate cells to restore visual function in different retinal degeneration processes. Retinal stem cells (RSCs) are good candidates to repair the retina and are present throughout the retina development, including adulthood. However, neonatal mouse RSCs derived from the radial glia population have a different potential to proliferate and differentiate in comparison to adult RSCs. Moreover, we observed that adult mouse RSCs, depending on the culture conditions, have a marked tendency to transform, whereas neonatal RSCs show subtle chromosome abnormalities only after extensive expansion. These characteristics should help to identify the optimal cell source and culture conditions for cell transplantation studies. These results will be discussed in light of other studies using RSCs as well as embryonic stem cells. Another important factor to consider is the host environment, which plays a crucial role for cell integration and which was poorly studied in the normal and the diseased retina. Nonetheless, important results were recently generated to reconsider cell transplantation strategy. Perspectives to enhance cell integration by manipulating the environment will also be presented.

Nuclear factor I-C links platelet-derived growth factor and transforming growth factor beta1 signaling to skin wound healing progression.

Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-beta signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-beta1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C(-/-) mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-beta in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration.

Prévalence de la dénutrition chez 143 adultes en bilan prétransplantation hépatique. Experience lausannoise de 1997 a 2005 [Prevalence of undernutrition in 143 patients before liver transplantation. The Lausanne experience between 1997 and 2005]

The prevalence of undernutrition was prospectively studied in 143 patients before liver transplantation between 1997 and 2005. Nutritional assessment is a particularly tricky problem in cirrhosis and mid-arm muscle circumference is considered as the best reliable anthropometric tool. In this prospective study, prevalence rate is very high (61%) and undernutrition is more frequent in alcoholic cirrhotic patients. In conclusion, these patients should benefit from an early dietician intervention before liver transplantation.

Renal transplantation following aorto-iliac reconstruction is a safe a strategy

Introduction: Renal transplantation is considered the treatment of choice for end-stage renal disease. However, the association of occlusive aorto-iliac disease and chronic renal failure is frequent and aorto-iliac reconstruction may be necessary prior to renal transplantation. This retrospective study reviews the results of this operative strategy.Material and Methods: Between January 2001 and June 2010, 309 patients underwent renal transplantation at our institution and 8 patients had prior aorto-iliac reconstruction using prosthetic material. There were 6 men and 2 women with a median age of 62 years (range 51-70). Five aorto-bifemoral and 2 aorto-bi-iliac bypasses were performed for stage II (n=5), stage IV (n=1) and aortic aneurysm (n=1). In one patient, iliac kissing stents and an ilio-femoral bypass were implanted. 4 cadaveric and 4 living donor renal transplantations were performed with an interval of 2 months to 10 years after revascularization.The results were analysed with respect of graft and patients survival. Differences between groups were tested by the log rank method.Results: No complications and no death occurred in the post-operative period. All bypasses remained patent during follow-up. The median time of post transplantation follow-up was 46 months for all patients and 27 months for patients with prior revascularization. In the revascularized group and control group, the graft and patient survival at 1 year were respectively 100%/96%, 100%/99% and at 5 years 86%/86%, 86%/94%, without significant differences between both groups.Discussion: Our results suggest that renal transplantation following prior aorto-iliac revascularisation with prosthetic material is safe and effective. Patients with end-stage renal disease and concomitant aorto-iliac disease should therefore be considered for renal transplantation. However, caution in the interpretation of the results is indicated due to the small sample size of our study.

Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study

Introduction: We previously reported the results of a phase II study for patients with newly diagnosed primary CNS lymphoma (PCNSL) treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and responseadapted whole brain radiotherapy (WBRT). The purpose of this report is to update the initial results and provide long-term data regarding overall survival, prognostic factors, and the risk of treatment-related neurotoxicity.Methods: A long-term follow-up was conducted on surviving primary central nervous system lymphoma patients having been treated according to the ,,OSHO-53 study", which was initiated by the Ostdeutsche Studiengruppe Hamatologie-Onkologie. Between August 1999 and October 2004 twentythree patients with an average age of 55 and median Karnofsky performance score of 70% were enrolled and received high-dose mthotrexate (HD-MTX) on days 1 and 10. In case of at least a partial remission (PR), high-dose busulfan/ thiotepa (HD-BuTT) followed by aPBSCT was performed. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. All patients (n=8), who are alive in 2011, were contacted and Mini Mental State examination (MMSE) and the EORTC QLQ-C30 were performed.Results: Eight patients are still alive with a median follow-up of 116,9 months (79 - 141, range). One of them suffered from a late relapse eight and a half years after initial diagnosis of PCNSL, another one suffers from a gall bladder carcinoma. Both patients are alive, the one with the relapse of PCNSL has finished rescue therapy and is further observed, the one with gall baldder carcinoma is still under therapy. MMSE and QlQ-C30 showed impressive results in the patients, who were not irradiated. Only one of the irradiated patients is still alive with a clear neurologic deficit but acceptable quality of life.Conclusions: Long-term follow-up of our patients, who were included in the OSHO-53 study show an overall survival of 30 percent. If WBRT can be avoided no long-term neurotoxicity has been observed and the patients benefit from excellent Quality of Life. Induction chemotherapy with two cycles of HD-MTX should be intensified to improve the unsatisfactory OAS of 30 percent.

Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.