tbuckley/cabot-search huggingface dataset:
Abstract 135: In Vitro Activity of Antimicrobial Drugs Against Clinically Relevant Bacterial Pathogens Under Mild Hypothermic Conditions
Authors: Christian Wallmüller, Herold Birger, Fritz Sterz, Athanasios Makristathis, Michael Ramharter
Journal: Circulation (2014)

Aim: Infections are a common problem in cardiac arrest survivors. Antimicrobial drugs are often administered in routine care during treatment of patients with mild therapeutic hypothermia. Since there is to date no evidence for the pharmacodynamics of antimicrobial drugs under mild therapeutic hypothermia conditions, we investigated the in vitro activity of common antimicrobials against clinically relevant bacterial pathogens. Methods: Activities of antimicrobial drugs against clinically relevant bacterial pathogens were assessed in vitro by disc diffusion and broth microdilution assays at normothermic (37°C) and hypothermic (32°C) conditions. Results: 73 bacterial isolates were tested in disc diffusion and 15 in broth microdilution assays. Mean differences in zone diameters and minimal inhibitory concentration ratios were 0.6 mm (95% confidence interval: 0.3-0.9 mm) and 0.98; (95% confidence interval: 0.95 - 1.02), respectively, meeting predefined criteria for equivalence of in vitro antimicrobial activity. Conclusion: The presented data provide reassuring evidence that the intrinsic activity of antimicrobials seems to be unaltered in mild therapeutic hypothermia. However, further studies evaluating the pharmacokinetics including target site concentrations of the respective drugs and in vivo pharmacodynamics are necessary to complement our understanding of the appropriate use of antimicrobials in mild therapeutic hypothermia
Luteinizing hormone/human chorionic gonadotrophin receptors in various epidermal structures
Authors: None Venencie, None Méduri, None Pissard, None Jolivet, None Loosfelt, None Milgrom, None Misrahi
Journal: British Journal of Dermatology (1999)

Two different monoclonal antibodies recognizing different epitopes were used to study the localization of luteinizing hormone/human chorionic gonadotrophin (LH/hCG) receptors in human skin. Immunolabelling was observed only in the epidermis and derived structures but not in the dermis. The basal, spinal and granular layers were stained, whereas no receptors were detected in the non-nucleated horny cells. In the growing (anagen) hair, immunostaining was found in the inner root sheath below the level of the sebaceous glands and in the outer root sheath above this level. In the resting (telogen) hair, only the latter staining was observed. In the sebaceous glands, only the thin cells close to the walls of the ducts were immunolabelled. In the eccrine sweat glands, the external clear cells were stained in the secretory portion of the gland, whereas only the cells close to the lumen were labelled in the ducts. The distribution of LH/hCG receptors was compared with that of steroidogenic enzymes (side chain cleavage cytochrome P450, adrenodoxin, 3-beta-hydroxy-5-ene steroid dehydrogenase Delta5-Delta4 isomerase, 17-hydroxylase cytochrome P450 and cytochrome P450 aromatase). Only partial overlaps were observed. The presence of LH receptor mRNA in the skin was confirmed by reverse transcription-polymerase chain reaction. Monoclonal antibodies raised against the human follicle-stimulating hormone receptor failed to detect the latter in the epidermal structures and in the dermis. The role of LH and hCG in skin modifications occurring during pregnancy and after the menopause is unknown. These hormones may possibly act by regulating steroidogenic enzymes or by modulating cell growth and differentiation.
New Themes in Palliative Care, by Ed David Clark, Jo Hockley, Sam Ahmedzai Making Palliative Care Better, by M Glickman
Authors: I. Peat
Journal: BMJ (1998)

An IV injection formulation of sodium dichloroacetate (DCA) was prepared without heat sterilization, and examined for stability. DCA is heat labile in aqueous solutions. Its decomposition involves dehalogenation and production of hydrogen ions. Decomposition occurs relatively rapidly at relatively low pH values, and is promoted by heating. Injection solutions should be prepared aseptically and sterilized by filtration. Solutions prepared aseptically and sterilized by filtration are stable stored at 4°C for at least four yrs.
Epidermal growth factor receptor signaling impairs the antiviral activity of interferon-alpha
Authors: Joachim Lupberger, François H.T. Duong, Isabel Fofana, Laetitia Zona, Fei Xiao, Christine Thumann, Sarah C. Durand, Patrick Pessaux, Mirjam B. Zeisel, Markus H. Heim, Thomas F. Baumert
Journal: Hepatology (2013)

Interferon-alpha (IFN-α) exhibits its antiviral activity through signal transducer and activator of transcription protein (STAT) signaling and the expression of IFN response genes (IRGs). Viral infection has been shown to result in activation of epidermal growth factor receptor (EGFR)-a host cell entry factor used by several viruses, including hepatitis C virus. However, the effect of EGFR activation for cellular antiviral responses is unknown. Here, we uncover cross-talk between EGFR and IFN-α signaling that has a therapeutic effect on IFN-α-based therapies and functional relevance for viral evasion and IFN resistance. We show that combining IFN-α with the EGFR inhibitor, erlotinib, potentiates the antiviral effect of each compound in a highly synergistic manner. The extent of the synergy correlated with reduced STAT3 phosphorylation in the presence of erlotinib, whereas STAT1 phosphorylation was not affected. Furthermore, reduced STAT3 phosphorylation correlated with enhanced expression of suppressors of cytokine signaling 3 (SOCS3) in the presence of erlotinib and enhanced expression of the IRGs, radical S-adenosyl methionine domain containing 2 and myxovirus resistance protein 1. Moreover, EGFR stimulation reduced STAT1 dimerization, but not phosphorylation, indicating that EGFR cross-talk with IFN signaling acts on the STATs at the level of binding DNA.Our results support a model where inhibition of EGFR signaling impairs STAT3 phosphorylation, leading to enhanced IRG expression and antiviral activity. These data uncover a novel role of EGFR signaling in the antiviral activity of IFN-α and open new avenues of improving the efficacy of IFN-α-based antiviral therapies.
Photodynamic therapy in acne: can we achieve therapeutic gain without pain?
Authors: C.A. Morton
Journal: British Journal of Dermatology (2011)

Conflicts of interest C.A.M. has acted as an adviser, lecturer and/or researcher for Galderma, Janssen and Leo Pharma. Impressive response rates have been observed following the use of topical photodynamic therapy (PDT) in acne, but the treatment remains little used in practice compared with its established indications in nonmelanoma skin cancer. Why? Therapy‐induced pain, erythema, sterile pustular reactions and hyperpigmentation, as well as the need for multiple treatments, have so far limited patient enthusiasm for PDT in acne. PDT, the interaction of a photosensitizer, light and oxygen to promote a targeted therapeutic effect, can promote improvement in acne via antibacterial activity against Propionibacterium acnes, as well as selective damage to sebaceous glands, reduction in follicular obstruction by keratinocyte shedding and via secondary host responses.1Propionibacterium acnes naturally produces small amounts of certain porphyrins, especially coproporphyrin III, hence the beneficial effects observed in light‐only studies, but application of an additional exogenous photosensitizer is necessary to maximize the effect of PDT in acne, facilitating its use even in moderate‐to‐severe disease.
426. Novel Chromatographic Process for the Purification of Recombinant Adeno-Associated Virus Pseudotypes
Authors: Hiroaki Mizukami, Jun Mimuro, Tsuyoshi Ogura, Takashi Okada, Akihiro Kume, Yoichi Sakata, Keiya Ozawa
Journal: Molecular Therapy (2004)

Currently, skeletal muscle and liver are the preferred target of gene transfer to supply transgene product into systemic circulation. Adipose tissue holds a number of attractive features as a target of gene transfer; it is one of the most abundant tissue in the body, and are designed to secrete various proteins physiologically, making it suitable to supply transgene product into systemic circulation. Of note, the transduced tissue can be safely removed without any sequelae in case of unexpected events. However, efficient transduction of adipose tissue has not been feasible by conventional methods. In order to develop a practical method, we tested the enhancement effect of the excipients upon gene transfer. At first, AAV vectors encoding LacZ were administered into adipose tissue of Db/Db mice. Widespread β-Gal expression was observed when a bio-compatible surfactant was included in the vector solution. To validate the efficacy of this method, vectors encoding mouse erythropoietin (Epo) were utilized. Two weeks following vector injection, significant concentrations of plasma Epo were observed and the levels were almost comparable to that of muscle- or liver- mediated gene transfer. Plasma Epo concentrations kept similar levels during the observation period thereafter. Increased blood hemoglobin levels warrant biological activity of adipocyte-derived Epo. Efficient expression was also confirmed by both immunofluorescence staining of the adipose tissue using anti-Epo antibody and RT-PCR. In addition, following complete removal of transduced adipose tissue, increased plasma Epo concentrations returned normal, suggesting that other tissues were not transduced by this method. Although the precise mechanisms of this phenomenon are yet to be analyzed, our method leads to efficient gene transfer into adipocytes, adding a novel choice for the supplemental gene therapy approaches.
Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease
Authors: Regina C. Betz, Benedikt G. H. Schoser, Dagmar Kasper, Kenneth Ricker, Alfredo Ramírez, Valentin Stein, Torberg Torbergsen, Young-Ae Lee, Markus M. Nöthen, Thomas F. Wienker, Jean-Pierre Malin, Peter Propping, André Reis, Wilhelm Mortier, Thomas J. Jentsch, Matthias Vorgerd, Christian Kubisch
Journal: Nature Genetics (2001)
CT guided biopsy of thoracic lesions
Authors: Mehrdad Bakhshayeshkaram, Pooyeh Graili, Soheyla Zahirifard
Journal: European Respiratory Journal (2011)

Purpose:  This study was designed to assess different variables of thoracic benign and malignant masses on Computed tomography (CT) guided biopsy and to identify the complication rate of procedure.   Materials and methods:  We evaluated 757 CT-guided biopsies of thoracic lesions performed from March 2004 to December 2008, retrospectively. All biopsies were performed by one radiologist. The CTs were assessed by a trained general practitioner for the size and location of lesions and pneumothorax diagnosis and then all CTs were double checked by the same radiologist. Lesions considered benign or malignant based on pathology reports.   Results:  Biopsy yielded sufficient tissue for pathologic examination in 612 cases (80.8%); 224 lesions (29.6%) were benign and 388 lesions (51.3%) were malignant (27 small cell and 233 non-small cell tumors). The most prevalent location of lesions was Right Upper Lobe (182 cases). 78 masses were located in mediastinum and 41 lesions in chest wall. 44.2% of benign lesions belonged to infectious (69.7% bacterial, 20.2% fungal, 6.1% hydatid cyst and 4% TB) and the rest were inflammatory masses (43.8%), granolomatus (5.8%) and neoplastic (6.2%) ones. The mean size of benign and malignant lesions were 6.011 and 7.481 cm, respectively (P.V.    Conclusion:  CT-guided needle biopsy seems to be a reliable diagnostic modality with low risk probability of complications for thoracic lesions.
Abstract 2398: Serum Uric Acid as a Risk Factor for Cardiovascular Disease in Countryside Patients with Essential Hypertension
Authors: Xiaohan Fan, Xiaomin Yang, Weili Zhang, Jianwei Wang, Yinhui Zhang, Kejia Lou, Ping Wang, Hu Wang, Xiaodong Song, Yibo Wang, Xiaojian Wang, Chunyan Fu, Yi Zheng, Xu Yang, Chunchang Qin, Yubao Zou, Haiying Wu, Xianliang Zhou, Shuxia Wang, Hongjian Wang, Gang Hu, Fuyuan Zhang, Jiyuan Wu, Luhong Wan, Rutai Hui
Journal: Circulation (2006)
Icodextrin skin rash incidence
Authors: Dimitra N. Biblaki, Vassilis C.H. Filiopoulos, Dimosthenis A. Vlassopoulos
Journal: Kidney International (2015)

To the Editor: We read with interest the case of an exfoliative rash related to icodextrin in the August 2014 issue nephrology image section and the reported incidence of about 10%.1Almiani M. Kohn O. Severe exfoliative skin rash with icodextrin.Kidney Int. 2014; 86: 449Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Our single-center experience with this complication in 86 consecutive patients on peritoneal dialysis over a period of 20 years with 43 (17 diabetics) exposed to icodextrin (median exposure time 29 months) is of only one case of icodextrin-related skin allergy (exfoliative rash) in a diabetic female, nine days after icodextrin initiation, resolving after solution withdrawal (incidence rate 2.3%). Skin rash incidence related to icodextrin use is variously reported up to 18.9%.2Wolfson M. Piraino B. Hamburger R.J. et al.A randomized controlled trial to evaluate the efficacy and safety of icodextrin in peritoneal dialysis.Am J Kidney Dis. 2002; 40: 1055-1065Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar Wolfson et al.3Wolfson M. Ogrinc F. Mujais S. Review of clinical trial experience with icodextrin.Kidney Int Suppl. 2002; 62: S46-S52Abstract Full Text Full Text PDF Scopus (28) Google Scholar metanalysis reported a higher rash incidence (10.1%) compared with controls (4.6%, P<0.003). On the opposite, in Cho et al.4Cho Y. Johnson D. Badve S. et al.Impact of icodextrin on clinical outcomes in peritoneal dialysis: a systematic review of randomized controlled trials.Nephrol Dial Transplant. 2013; 28: 1899-1907Crossref PubMed Scopus (66) Google Scholar metanalysis, rash risk is not increased under icodextrin, discontinued only in up to 4.3% of patients. Icodextrin solution is an important tool in peritoneal dialysis improving ultrafiltration and reducing exposure to glucose. In our experience rash incidence was low. The wide variation in the complication’s reported incidence may represent an overestimation taking into account skin manifestations of various origins, common in uremia.
Nebulised 7% hypertonic saline improves health related quality of life in patients with non-cystic fibrosis bronchiectasis
Authors: Rachel Johnston, Fiona Shaw, Robert Wilson, Michael Loebinger, Lizzie Flude
Journal: European Respiratory Journal (2011)

Introduction: Cough and sputum have a significant impact on quality of life (QoL) in non-cystic fibrosis bronchiectasis (NCFBx). Nebulised 7% hypertonic saline (HTS) has previously been shown to improve airway clearance in NCFBx, and we hypothesised that it would also improve QoL in such patients.

Method: Patients with NCFBx referred for HTS over a 4 month period at Royal Brompton Hospital were included (N=22). Patients were assessed by the Leicester cough questionnaire (LCQ) as a marker for Health Related Quality of Life (HRQol), Visual Analogue Scale for ease of clearance (VASEoC) and FEV1 pre and post 1 month use of HTS. Results are expressed as median and interquartile range and Wilcoxon-signed Rank tests were used to assess the impact of the therapy.

Results: N=22 (Male=7), median age 64yrs (32-81), FEV1 1.59 (0.64-3.01). There was a significant improvement in LCQ 11.0 (9.2-14.7) to 16.7 (10.7-17.7) p=0.01 and VASEoC 7 (5.5- 8) to 4.7 (3-7) p=0.002. There was no significant change in FEV1(p=0.32). 4 patients (18%) constricted on challenge test, and were not included in analysis. No other adverse effects of the therapy were seen.

Conclusion: In addition to confirming that HTS improves airway clearance, we demonstrated for the first time that HTS also improves HRQol markers in patients with NCFBx. The minimal clinical significant difference in the LCQ is reported to be 1.3-2.7. There was therefore a statistically and clinically significant change in the total LCQ score, suggesting HRQol significantly improved with one month use of HTS. Further trials with HTS are needed to assess whether these improvements are sustained long term in such patients.
Abstract 4052: Targeting PDK1 in breast cancer: kinase-dependent regulation of tumor growth and kinase-independent regulation of cell migration and invasion
Authors: Paolo Armando Gagliardi, Laura di Blasio, Giorgio Seano, Roberto Sessa, Alberto Puliafito, Federico Bussolino, Luca Primo
Journal: Cancer Research (2014)

Abstract 3-Phosphoinositide Dependent Kinase 1 (PDK1) is the kinase that phosphorylates the activation loop of several protein kinases such as Akt, PKC or SGK. In breast carcinomas PDK1 was found frequently overexpressed and this correlates with a more aggressive phenotype. This study is aimed to understand the role of PDK1 in breast tumor progression and the molecular mechanisms involved. Using stable gene silencing and kinase inhibitors, we studied PDK1 role in different in vitro and in vivo assays including anchorage independent growth, anoikis, xenografts, migration and invasion assays. In our study we found that PDK1 promotes resistance to anoikis, anchorage independent growth and tumor growth in breast cancer cell lines through the phosphorylation of its substrates, since the kinase-dead mutant abrogates all the PDK1-mediated effects. For this reasons either PDK1 gene silencing or its kinase inhibition with small compounds are sufficient to promote anoikis, to reduce anchorage independent growth and tumor growth. We also found that PDK1 silencing is able to reduce, while its overexpression to increase, cell migration and invasion in mammary cells. Surprisingly, the regulation of cell migration is operated in a kinase independent manner. In fact PDK1 kinase inhibitor failed to recapitulate the effects of gene silencing in cell migration. The molecular mechanism, underlying this unconventional kinase-independent regulation of cell migration, involves the binding of PDK1 to Myotonic Dystrophy kinase-related Cdc42-binding Kinase α (MRCKα). This binding increases MRCKα kinase activity on Myosin Light Chain-2 (MLC2) and on myosin phosphatase target subunit 1 (MyPT1). Both these phosphorylations increase of non-muscular myosin activity, which is required to pull forward the cell body during directional migration and invasion. In summary, our findings unveil that PDK1 regulates tumor growth, survival in absence of adhesion, resistance to anoikis, but also migration and invasion of breast cancer cells by two different mechanisms. These findings should be taken in account for a rational targeting of PDK1 in cancer. Citation Format: Paolo Armando Gagliardi, Laura di Blasio, Giorgio Seano, Roberto Sessa, Alberto Puliafito, Federico Bussolino, Luca Primo. Targeting PDK1 in breast cancer: kinase-dependent regulation of tumor growth and kinase-independent regulation of cell migration and invasion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4052. doi:10.1158/1538-7445.AM2014-4052
PROGNOSIS AND TREATMENT OF ERYSIPELAS
Authors: John A. Toomey
Journal: Annals of Internal Medicine (1938)

Article1 August 1938PROGNOSIS AND TREATMENT OF ERYSIPELASJOHN A. TOOMEY, M.D., F.A.C.P.JOHN A. TOOMEY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-12-2-166 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMortality statistics are the only sources of factual information not affected by the personal equation.From 1912 to 1933, Hoyne in Chicago had a mortality rate of 12.47 per cent in 5,666 cases of erysipelas; from 1929 to 1933, it was 13.4 per cent in 1,193 cases. From 1927 to 1931, Gordon and Young1in Detroit had 1,156 cases with a mortality rate of 9.5 per cent. In Bellevue Hospital, in New York City, from 1904 to 1937, there were 15,277 cases with a mortality rate of 10.1 per cent.2Symmers2stated that in 3,311 cases admitted to the same...Bibliography1. GORDONYOUNG JEDC: Treatment of erysipelas with erysipelas streptococcus antitoxin, Jr. Michigan Med. Soc., 1929, xxviii, 353. Google Scholar2. SYMMERS D: Antitoxin treatment of erysipelas; results in 705 cases at Bellevue Hospital, Jr. Am. Med. Assoc., 1928, xci, 535. CrossrefGoogle Scholar3. U. S. Department of Commerce, Mortality Statistics. Google Scholar4. BIRKHAUG KE: Erysipelas, Nelson's Loose Leaf Medicine, Chap. 16, pg. 447 et seq. Google Scholar5. BIRKHAUG KE: Erysipelas: Etiology and treatment with erysipelas antistreptococcic serum, Jr. Am. Med. Assoc., 1926, lxxxvi, 1411. CrossrefGoogle Scholar6. MCCANN WS: Serum treatment of erysipelas, Jr. Am. Med. Assoc., 1928, xci, 78. CrossrefGoogle Scholar7. ELEY RC: Treatment of erysipelas in infants; report of 33 cases treated with antistreptococcus (erysipelas) serum, Am. Jr. Dis. Child., 1930, xxxix, 529. CrossrefGoogle Scholar8. BLACKFAN K: Personal communication to Birkhaug, K. E., 1928. Google Scholar9. LONGBLISS HEA: Para-amino-benzene-sulfonamide and its derivatives; experimental and clinical observations on their use in treatment of beta-hemolytic streptococcic infection; preliminary report, Jr. Am. Med. Assoc., 1937, cviii, 32. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Lakewood, Ohio*Delivered before the American College of Physicians, New York City, April 6, 1938.From the Department of Pediatrics, Western Reserve University, and the Division of Contagious Diseases, City Hospital, Cleveland, Ohio. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPyodermienThe clinical diagnosis of dermatological lesions of the face and oral cavity 1 August 1938Volume 12, Issue 2Page: 166-177KeywordsDeath ratesMortalityPediatrics Issue Published: 1 August 1938 PDF downloadLoading ...