Dr Patricia Clugston-A Spirit of Determination.

Dr Patricia Clugston was a British Columbia native who completed her plastic surgery residency training in Vancouver in 1993 before pursuing a fellowship in Nashville with Dr Patrick Maxwell in 1994. When Dr Clugston returned to Vancouver, she helped to establish a comprehensive and renowned breast reconstruction program. She spent her career advocating for and working towards better treatment options for women seeking breast reconstruction. As a determined surgeon and accomplished athlete, Dr Clugston was truly a tour de force in all aspects of her life. Patty, as she was affectionately known by her colleagues, loved her job. Dr Clugston was an avid advocate for medical education and an outstanding clinical researcher and speaker that established her as a shining star in Canadian plastic surgery. Patty had always lived life to the fullest and was determined that scleroderma would not change this. Her sharp wit, intellectual curiosity, and pragmatism masked an incredible courage as she fought bravely against a cruel disease. Dr Clugston died on March 1, 2005, at the age of 46 surrounded by the loving company of her husband, friends, and family at the Vancouver General Hospital. The Dr Patricia Clugston Chair in Breast Reconstruction was established in her name to honour her legacy and continue to improve the care of patients with breast cancer.

Originaire de la Colombie-Britannique, la docteure Patricia Clugston a terminé sa résidence en plasturgie à Vancouver en 1993 avant d'effectuer des études postdoctorales à Nashville avec le docteur Patrick Maxwell en 1994. À son retour à Vancouver, elle a contribué à mettre sur pied un programme de reconstruction mammaire complet et réputé. Elle a consacré sa carrière à préconiser et à rechercher de meilleures possibilités thérapeutiques pour les femmes qui veulent une reconstruction mammaire. Chirurgienne déterminée et athlète accomplie, elle dominait dans tous les aspects de sa vie. Patty, comme l'appelaient affectueusement ses collègues, adorait son travail. Cette défenseure passionnée de l'enseignement de la médecine était une chercheuse clinicienne et une conférencière remarquable, ce qui l'a établie comme une tête d'affiche de la plasturgie au Canada. Elle a toujours vécu sa vie au maximum et était déterminée à ne pas laisser la sclérodermie y changer quelque chose. Sa vivacité d'esprit, sa curiosité intellectuelle et son pragmatisme cachaient un courage incroyable, car elle luttait contre une maladie cruelle. Elle est décédée le 1er mars 2005 au Vancouver General Hospital à l'âge de 46 ans, entourée de l'amour de son mari, de ses amis et de sa famille. La chaire Dre Patricia Clugston en reconstruction mammaire a été créée en son nom pour commémorer sa mémoire et continuer d'améliorer les soins aux patientes atteintes du cancer du sein.

Reporting Outcomes and Outcome Measures in Thumb Carpometacarpal Joint Osteoarthritis: A Systematic Review.

PURPOSE: In the thumb carpometacarpal (CMC) joint osteoarthritis (OA) literature, there is substantial heterogeneity in outcome and outcome measure reporting. This could be rectified by a standardized core outcome set (COS). This study aimed to identify a comprehensive list of outcomes and outcome measures for thumb CMC joint OA, which represents the first step in developing a COS. METHODS: A computerized search of MEDLINE, EMBASE, Cochrane, and CINAHL was performed to identify randomized controlled trials, as well as observational studies involving at least 50 participants aged greater than 18 years undergoing surgery for thumb CMC joint OA. Reported outcomes and outcome measures were extracted from these trials and summarized. RESULTS: This search yielded 3,498 unique articles, 97 of which were used for analysis. A total of 33 unique outcomes and 25 unique outcome measures were identified. The most frequently used outcomes were complications (78), postoperative pain (73), radiologic outcomes (64), and grip strength (63). Within each reported outcome, there was substantial variation in how the outcome was measured. Of the 25 unique outcome measures, 10 were validated. Of the remaining 15, 12 were created ad hoc by the author. The Disabilities of the Arm, Shoulder, and Hand questionnaire was the most commonly reported outcome measure (34%). CONCLUSIONS: There is a lack of consensus on critical outcomes after surgery for thumb CMC joint OA. A standardized COS created by stakeholder consensus would improve the consistency and therefore the quality of future research. CLINICAL RELEVANCE: This systematic review of outcomes represents the first step in developing a core outcome set for thumb CMC joint OA.

Qualitative and Semiquantitative Analysis of Doping Products Seized at the Swiss Border.

BACKGROUND: Substances developed for therapeutic use are also known to be misused by athletes as doping agents and, outside of regulated sport, for image-enhancement. This has generated a market for counterfeit doping substances. Counterfeit doping agents may be of poor pharmaceutical quality and therefore constitute health risks to consumers. OBJECTIVES: This study aims to investigate the pharmaceutical quality of 1,190 doping products seized at the Swiss border. METHODS: Swiss customs authorities seize incoming shipments potentially containing doping agents. Qualitative and semiquantitative analyses were performed in order to test for prohibited doping substances. The main analytical methods utilized for characterizing confiscated compounds were liquid chromatography-high resolution mass spectrometry, polyacrylamide gel electrophoresis with subsequent in-gel tryptic digestion and identification of peptidic compounds using nanoliquid chromatography-tandem mass spectrometry, and electrochemiluminescence immuno assay. RESULTS: For 889 (75%) of the analyzed products, the label suggested the content of anabolic agents, for 146 samples (12%) peptide hormones or growth factors, and for 113 items (9%) antiestrogens, aromatase inhibitors or other metabolic modulators. For the majority of the investigated products, the pharmaceutical quality was an unsatisfactory standard: nonapproved substances were detected and less than 20% of the products contained the claimed substance in the respective amount. CONCLUSION: A comprehensive sample of confiscated doping products was analyzed, allowing for monitoring of developments regarding the use of doping substances in Switzerland and for anticipating future trends and challenges in sports drug testing. An alarming number of tested products was of substandard pharmaceutical quality.

Detection of the diuretic hydrochlorothiazide in a doping control urine sample as the result of a non-steroidal anti-inflammatory drug (NSAID) tablet contamination.

Hydrochlorothiazide (HCTZ, 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide-1,1-dioxide) belongs to the class of diuretic agents that represent one of today's cornerstones of the treatment of hypertensive patients. In addition to its clinical relevance, HCTZ is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA) at all times and has frequently been detected in sports drug testing urine samples worldwide since its ban was introduced in 1988. Despite these facts, the adverse analytical finding concerning HCTZ in an in-competition routine doping control sample collected in December 2014 was further investigated, particularly motivated by the comparably low urinary concentration of the drug accounting for approximately 5ng/mL. The athlete in question did not declare the use of any nutritional supplement or medication other than the ingestion of a non-steroidal anti-inflammatory drug (NSAID) prior to competition. Hence, the drug (formulated as coated tablet) provided by the athlete as well as the corresponding retention sample of the manufacturer were analyzed. Noteworthy, both samples confirmed the presence of about 2µg of HCTZ per tablet. In order to further probe for the plausibility of the observed urinary HCTZ concentrations with the scenario of drug ingestion and subsequent doping control sample collection, administration studies with produced HCTZ-spiked placebo-tablets (2.5µg of HCTZ/tablet) were conducted. Urine specimens were collected prior to and after ingestion of the drug and subjected to routine doping control analytical procedures employing liquid chromatography/tandem mass spectrometry. While blank urine samples returned negative test results, post-administration specimens were found to contain HCTZ at concentrations of approximately 1-16ng/mL, which supported the athlete's inadvertent intake of HCTZ via contaminated NSAID tablets. Due to the substantial sensitivity of test methods employed today by doping control laboratories, even drug contaminations ranging within the good manufacturing practice (GMP) limit of 10ppm overall carry-over can evidently lead to adverse analytical findings. This calls into question whether selected (classes of) substances such as diuretics should be reported only when exceeding a defined reporting level and/or whether adverse analytical findings of non-threshold substances should be reported with an estimated semi-quantitative concentration of the identified substance to facilitate the result management by anti-doping organizations.

Water availability as dominant control of heat stress responses in two contrasting tree species.

Heat waves that trigger severe droughts are predicted to increase globally; however, we lack an understanding of how trees respond to the combined change of extreme temperatures and water availability. Here, we studied the impacts of two consecutive heat waves as well as post-stress recovery in young Pseudotsuga menziesii (Mirb.) Franco (Douglas-fir) and Robinia pseudoacacia L. (black locust) growing under controlled conditions. Responses were compared under water supply close to the long-term average and under reduced irrigation to represent drought. Exposure to high temperatures (+10 °C above ambient) and vapour pressure deficit strongly affected the trees in terms of water relations, photosynthesis and growth. Douglas-fir used water resources conservatively, and transpiration decreased in response to mild soil water limitation. In black locust, heat stress led to pronounced tree water deficits (stem diameter shrinkage), accompanied by leaf shedding to alleviate stress on the hydraulic system. The importance of water availability during the heat waves became further apparent by a concurrent decline in photosynthesis and stomatal conductance with increasing leaf temperatures in both species, reaching the lowest rates in the heat-drought treatments. Stress severity determined both the speed and the amount of recovery. Upon release of stress, photosynthesis recovered rapidly in drought-treated black locust, while it remained below control rates in heat (t = -2.4, P < 0.05) and heat-drought stressed trees (t = 2.96, P < 0.05). In Douglas-fir, photosynthesis recovered quickly, while water-use efficiency increased in heat-drought trees because stomatal conductance remained reduced (t = -2.92, P < 0.05). Moreover, Douglas-fir was able to compensate for stem-growth reductions following heat (-40%) and heat-drought stress (-68%), but most likely at the expense of storage and other growth processes. Our results highlight the importance of studying heat waves alongside changes in water availability. They further suggest that we should look beyond the actual stress event to identify lagged effects and acclimation processes that may determine tree resilience in the long term.

Seizures of doping substances at the Swiss Border--a descriptive investigation.

This retrospective study evaluates the content, the destination and the source of 960 postal items seized by the Swiss customs authorities at the Swiss border between 2013 and 2014. The packages were seized because they contained at least one prohibited doping product as identified by the Swiss law on encouraging sports and physical activity. A total number of 1825 different doping products were confiscated from these parcels, accounting for an average of 1.9 doping products per seized item. In 74% of the cases, where seizures were made, anabolic androgenic steroids, mostly testosterone esters, were discovered. An obvious trading channel for doping products was identified in this study. The seized compounds were predominately manufactured in Asian countries, but sent to Switzerland mostly via South Eastern Europe countries. Due to the unique collaboration between the Swiss customs authorities and the national anti-doping agency, this study uncovered an alarming trend of illegal doping product trafficked to Switzerland.

Quantification of encapsulated bioburden in spacecraft polymer materials by cultivation-dependent and molecular methods.

Bioburden encapsulated in spacecraft polymers (such as adhesives and coatings) poses a potential risk to jeopardize scientific exploration of other celestial bodies. This is particularly critical for spacecraft components intended for hard landing. So far, it remained unclear if polymers are indeed a source of microbial contamination. In addition, data with respect to survival of microbes during the embedding/polymerization process are sparse. In this study we developed testing strategies to quantitatively examine encapsulated bioburden in five different polymers used frequently and in large quantities on spaceflight hardware. As quantitative extraction of the bioburden from polymerized (solid) materials did not prove feasible, contaminants were extracted from uncured precursors. Cultivation-based analyses revealed <0.1-2.5 colony forming units (cfu) per cm3 polymer, whereas quantitative PCR-based detection of contaminants indicated considerably higher values, despite low DNA extraction efficiency. Results obtained from this approach reflect the most conservative proxy for encapsulated bioburden, as they give the maximum bioburden of the polymers irrespective of any additional physical and chemical stress occurring during polymerization. To address the latter issue, we deployed an embedding model to elucidate and monitor the physiological status of embedded Bacillus safensis spores in a cured polymer. Staining approaches using AlexaFluor succinimidyl ester 488 (AF488), propidium monoazide (PMA), CTC (5-cyano-2,3-diotolyl tetrazolium chloride) demonstrated that embedded spores retained integrity, germination and cultivation ability even after polymerization of the adhesive Scotch-Weld 2216 B/A. Using the methods presented here, we were able to estimate the worst case contribution of encapsulated bioburden in different polymers to the bioburden of spacecraft. We demonstrated that spores were not affected by polymerization processes. Besides Planetary Protection considerations, our results could prove useful for the manufacturing of food packaging, pharmacy industry and implant technology.

Enzyme-functionalized biomimetic apatites: concept and perspectives in view of innovative medical approaches.

Biomimetic nanocrystalline calcium-deficient apatite compounds are particularly attractive for the setup of bioactive bone-repair scaffolds due to their high similarity to bone mineral in terms of chemical composition, structural and substructural features. As such, along with the increasingly appealing development of moderate temperature engineered routes for sample processing, they have widened the armamentarium of orthopedic and maxillofacial surgeons in the field of bone tissue engineering. This was made possible by exploiting the exceptional surface reactivity of biomimetic apatite nanocrystals, capable of easily exchanging ions or adsorbing (bio)molecules, thus leading to highly-versatile drug delivery systems. In this contribution we focus on the preparation of hybrid materials combining biomimetic nanocrystalline apatites and enzymes (lysozyme and subtilisin). This paper reports physico-chemical data as well as cytotoxicity evaluations towards Cal-72 osteoblast-like cells and finally antimicrobial assessments towards selected strains of interest in bone surgery. Biomimetic apatite/enzyme hybrids could be prepared in varying buffers. They were found to be non-cytotoxic toward osteoblastic cells and the enzymes retained their biological activity (e.g. bond cleavage or antibacterial properties) despite the immobilization and drying processes. Release properties were also examined. Beyond these illustrative examples, the concept of biomimetic apatites functionalized with enzymes is thus shown to be useable in practice, e.g. for antimicrobial purposes, thus widening possible therapeutic perspectives.

Awareness of human papillomavirus infection, genitoanal warts and cancer in a dermatological outpatient clinic setting.

There has been little research into awareness of human papillomavirus (HPV) among dermatological out-patients, despite the fact that management of HPV infection causing genitoanal warts/cancer is part of the routine practice of dermato-venereologists. The aim of this study was to explore awareness of HPV among dermatological outpatients. A self-administered questionnaire was distributed to 360 consecutive attendees of a Munich dermatological outpatient clinic in November 2009. Of the total number of questionnaires, 77.2% were returned, and 69.7% (n=251, 51.8% females) were included in the analysis. 39.4% of the respondents had heard of HPV infection, and 23.9% of vaccination. Of those who had heard of HPV, 81.8% knew that HPV risk is associated with non-use condoms, number of sexual partners (77.8%), smoking (8.1%), and that HPV causes genital warts (65.7%), anal warts (39.4%) and cervical cancer (57.6%). HPV ignorance (never having heard of HPV) was predicted by being male (adjusted odds ratio=2.23, 95% confidence interval=1.32-3.80) and being a parent (adjusted odds ratio=2.11, 95% confidence interval=1.24-3.59). We conclude that dermatological outpatients have insufficient knowledge of HPV, its sequelae and prevention.

Evaluation of a gas sensor array and pattern recognition for the identification of bladder cancer from urine headspace.

Previous studies have indicated that volatile compounds specific to bladder cancer may exist in urine headspace, raising the possibility that headspace analysis could be used for diagnosis of this particular cancer. In this paper, we evaluate the use of a commercially available gas sensor array coupled with a specifically designed pattern recognition algorithm for this purpose. The best diagnostic performance that we were able to obtain with independent test data provided by healthy volunteers and bladder cancer patients was 70% overall accuracy (70% sensitivity and 70% specificity). When the data of patients suffering from other non-cancerous urological diseases were added to those of the healthy controls, the classification accuracy fell to 65% with 60% sensitivity and 67% specificity. While this is not sufficient for a diagnostic test, it is significantly better than random chance, leading us to conclude that there is useful information in the urine headspace but that a more informative analytical technique, such as mass spectrometry, is required if this is to be exploited fully.

Antiangiogenic strategies in medulloblastoma: reality or mystery.

Medulloblastoma is the most common malignant brain tumor of childhood. Surgery, radiation therapy, and chemotherapy successfully cure many patients, but survivors can suffer long-term toxicities affecting their neurocognitive and growth potential; furthermore, there is no curative therapy in up to 30% of cases, mainly because of our incomplete understanding of many of the underlying molecular and cellular processes. Angiogenesis is a hallmark of the progression of medulloblastoma and, over the last years, investigators have sought to develop effective and less toxic antiangiogenic strategies, including the inhibition or destruction of abnormal blood vessels using either antiangiogenic or vascular disrupting agents. However, the results are conflicting principally because of the complex biology of tumor vasculature and the irregular geometry of the vascular system in real space. In addition, current targets of antiangiogenic therapy, such as vascular endothelial growth factor (VEGF), are thought to be critical for both physiologic and pathologic angiogenesis, and clinical side effects of anti-VEGF therapy are beginning to emerge. We here review the state-of-the-art concerning antiangiogenic targets for medulloblastoma treatment, and discuss the complexity of the vascular system that intrinsically limits the efficacy of current strategies.

Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases.

AIM: To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3beta), CCL20 (MIP-3alpha) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (HCC) versus colorectal liver metastases (CRLM) and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases. METHODS: Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent non-tumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RT-PCR and Western blot analysis in the same cases of HCC and CRLM. RESULTS: Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20 demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly up-regulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues. CONCLUSION: Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked up-regulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.

Mortality and morbidity in extremely preterm infants (22 to 26 weeks of gestation): Austria 1999-2001.

OBJECTIVE: The aim of this retrospective study was to analyze the mortality and morbidity for extremely preterm infants with a gestational age from 22 to 26 weeks. All infants were born in Austria during the years 1999-2001. METHODS: Data were collected from 16 neonatal intensive care units in Austria. Main outcome criteria were mortality, the rates of chronic lung disease (CLD) and severe retinopathy of prematurity (ROP, stage > or =3) to determine the short-term outcome; the rate of cerebral palsy (CP) at the corrected age of twelve months to assess the long-term outcome. RESULTS: Overall, 796 preterm infants with a gestational age less than 27 weeks were born in Austria and 581 (73%) were registered as live-born infants. Of those live born, 508 (87%) were analyzed. The mortality rates were 83%, 76%, 43%, 26% and 13% for 22, 23, 24, 25 and 26 weeks' gestation, respectively. The rates of CLD were 33% (22 weeks), 36% (23 weeks), 42% (24 weeks), 31% (25 weeks) and 22% (26 weeks). The rates of ROP of stage > or =3 were 0% (22 weeks), 29% (23 weeks), 23% (24 weeks), 18% (25 weeks) and 10% (26 weeks). The rates of CP at the corrected age of 12 months were 33%, 50%, 33%, 26% and 25% for 22, 23, 24, 25 and 26 weeks' gestation, respectively. CONCLUSIONS: The results of this national study are in accordance with the international literature: mortality and morbidity increased with decreasing gestational age.