tbuckley/cabot-search huggingface dataset:
Congenital erythropoietic porphyria associated with myelodysplasia presenting in a 72-year-old man: report of a case and review of the literature
Authors: A.P. Kontos, D. Ozog, C. Bichakjian, H.W. Lim
Journal: British Journal of Dermatology (2003)

Journal Article Congenital erythropoietic porphyria associated with myelodysplasia presenting in a 72‐year‐old man: report of a case and review of the literature Get access A.P. Kontos, A.P. Kontos Department of Dermatology, Henry Ford Health System, Detroit, MI U.S.A Search for other works by this author on: Oxford Academic Google Scholar D. Ozog, D. Ozog Department of Dermatology, Henry Ford Health System, Detroit, MI U.S.A Search for other works by this author on: Oxford Academic Google Scholar C. Bichakjian, C. Bichakjian Department of Dermatology, University of Michigan, Ann Arbor, MI U.S.A Search for other works by this author on: Oxford Academic Google Scholar H.W. Lim H.W. Lim Department of Dermatology, Henry Ford Health System, Detroit, MI U.S.A Henry W. Lim, MD, Department of Dermatology, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, U.S.A. E‐mail: hlim1@hfhs.org Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 1, 1 January 2003, Pages 160–164, https://doi.org/10.1046/j.1365-2133.2003.05040.x Published: 01 January 2003 Article history Accepted: 10 June 2002 Published: 01 January 2003
Effect of Fructose on Alcohol Concentrations in the Blood in Man
Authors: Leah M. Lowenstein
Journal: JAMA (1970)

Fructose has previously been found to be the most effective experimental compound in increasing the metabolism of alcohol (ethanol). In this clinical study, fructose, glucose, or saline infusions were administered intravenously to subjects who simultaneously drank 300 ml of bourbon. Fructose infusions resulted in a lowering of the alcohol levels in the blood by 43% compared to the values obtained during saline solution infusions. Glucose infusions were ineffective. The lowering of the alcohol levels by fructose may occur because the dissociation of the alcohol dehydrogenase-NADH complex is accelerated by intermediary metabolites of fructose.
Relevance of congenital melanocytic naevi in vitiligo
Authors: N. van Geel, L. Van Poucke, B. Van de Maele, R. Speeckaert
Journal: British Journal of Dermatology (2014)

Background Some case reports concerning the concomitant presence of congenital melanocytic naevi (CMN), halo naevi and vitiligo have been published. However, their possible link has never been investigated in a large patient population. Objectives To evaluate the relevance of CMN in patients with vitiligo with respect to the presence of halo naevi and some general clinical variables such as age of onset, Koebner phenomenon and body surface area (BSA) involvement. Methods In total, 1004 patients with vitiligo (nonsegmental) and 291 control patients were included in this observational study. CMN were scored in size, location and halo formation, and classified into clinical convincing or possible lesions. Results Convincing CMN were present in 3·3% of the patient population and in 1·0% of the control population. The presence of halo naevi was significantly higher (P = 0·01) and age of onset of vitiligo was significantly lower (P < 0·01) in the presence of CMN. Halo formation around the CMN, as observed in 30·3% of cases, was associated with a higher diameter of the CMN. Patients with congenital naevi had a particular predisposition to having lesions on joints/acral areas and reported more often signs of Koebner phenomenon (P = 0·01). No clear difference in disease activity, BSA involvement, associated autoimmune diseases or treatment response was observed in patients with vitiligo with or without congenital naevi. Conclusions This study provides clinical evidence that CMN may influence the age of onset of vitiligo and trigger the development of halo naevi in patients with vitiligo.
Treatment of Haemophilus influenzae Meningitis
Authors: Thomas F. Paine
Journal: JAMA (1978)

To the Editor.—  Thank goodness we can fall back on streptomycin plus sulfisoxazole for treating ampicillinresistant Haemophilus influenzae meningitis, as noted by Richard H. Meade III, MD (239:324, 1978). He recommended that the streptomycin sulfate be injected intrathecally for three doses, intravenously for one dose, and then intramuscularly for 14 days.  The only bone I would pick with this method of treatment is the use of streptomycin intravenously. Considerable experience in earlier days 1 showed that intrathecal plus intramuscular streptomycin was adequate for treating bacterial meningitis caused by susceptible microorganisms. In those days we worried about possible immediate systemic reactions that could follow intravenous streptomycin injections; perhaps such reactions are no longer a problem with current crystalline preparations of streptomycin. Another point is that an initial intravenous dose is probably not necessary, provided an initial intrathecal dose is administered and intramuscular dosage is begun at the same time. Blood levels are
Regulation of mitochondrial permeability transition pore by PINK1
Authors: Clement A Gautier, Emilie Giaime, Erica Caballero, Lucía Núñez, Zhiyin Song, David Chan, Carlos Villalobos, Jie Shen
Journal: Molecular Neurodegeneration (2012)

Abstract Background Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) have been linked to familial Parkinson’s disease, but the underlying pathogenic mechanism remains unclear. We previously reported that loss of PINK1 impairs mitochondrial respiratory activity in mouse brains. Results In this study, we investigate how loss of PINK1 impairs mitochondrial respiration using cultured primary fibroblasts and neurons. We found that intact mitochondria in PINK1 −/− cells recapitulate the respiratory defect in isolated mitochondria from PINK1 −/− mouse brains, suggesting that these PINK1 −/− cells are a valid experimental system to study the underlying mechanisms. Enzymatic activities of the electron transport system complexes are normal in PINK1 −/− cells, but mitochondrial transmembrane potential is reduced. Interestingly, the opening of the mitochondrial permeability transition pore (mPTP) is increased in PINK1 −/− cells, and this genotypic difference between PINK1 −/− and control cells is eliminated by agonists or inhibitors of the mPTP. Furthermore, inhibition of mPTP opening rescues the defects in transmembrane potential and respiration in PINK1 −/− cells. Consistent with our earlier findings in mouse brains, mitochondrial morphology is similar between PINK1 −/− and wild-type cells, indicating that the observed mitochondrial functional defects are not due to morphological changes. Following FCCP treatment, calcium increases in the cytosol are higher in PINK1−/− compared to wild-type cells, suggesting that intra-mitochondrial calcium concentration is higher in the absence of PINK1. Conclusions Our findings show that loss of PINK1 causes selective increases in mPTP opening and mitochondrial calcium, and that the excessive mPTP opening may underlie the mitochondrial functional defects observed in PINK1 −/− cells.
A highly Stable and Nonintegrated Human Artificial Chromosome (HAC) Containing the 2.4 Mb Entire Human Dystrophin Gene
Authors: Hidetoshi Hoshiya, Yasuhiro Kazuki, Satoshi Abe, Masato Takiguchi, Naoyo Kajitani, Yoshinori Watanabe, Toko Yoshino, Yasuaki Shirayoshi, Katsumi Higaki, Graziella Messina, Giulio Cossu, Mitsuo Oshimura
Journal: Molecular Therapy (2008)

Episomal vector with the capacity to deliver a large gene containing all the critical regulatory elements is ideal for gene therapy. Human artificial chromosomes (HACs) have the capacity to deliver an extremely large genetic region to host cells without integration into the host genome, thus preventing possible insertional mutagenesis and genomic instability. Duchenne muscular dystrophy (DMD) is caused by mutation in the extremely large dystrophin gene (2.4 Mb). We herein report the development of a HAC vector containing the entire human dystrophin gene (DYS-HAC) that is stably maintained in mice and human immortalized mesenchymal stem cells (hiMSCs). The DYS-HAC was transferred to mouse embryonic stem (ES) cells, and isoforms of the DYS-HAC-derived human dystrophin in the chimeric mice generated from the ES cells were correctly expressed in tissue-specific manner. Thus, this HAC vector containing the entire dystrophin gene with its native regulatory elements is expected to be extremely useful for future gene and cell therapies of DMD.
On the Administration of Chloride of Ethyl and Somnoform, Alone or in Conjunction with Nitrous Oxide or Ether
Authors: G. W. B. Daniell
Journal: BMJ (1904)

949that, provided a culture of this cocco-bacillus is of suifficient virulelnce, it is possible to count upon the destructioni by its use of all the rats in a large city without can,ing any daniget whatever to its other inhabitants, lhuman or animal, always supposing that the operations are conducted in an orderly and methodical manner.
Studies Needed to Address Public Health Challenges of the 2009 H1N1 Influenza Pandemic: Insights from Modeling
Authors: Maria D. Van Kerkhove, Tommi Asikainen, Niels G. Becker, Steven Bjorge, Jean-Claude Desenclos, Thais dos Santos, Christophe Fraser, Gabriel M. Leung, Marc Lipsitch, Ira M. Longini, Emma S. McBryde, Cathy E. Roth, David K. Shay, Derek J. Smith, Jacco Wallinga, Peter J. White, Neil M. Ferguson, Steven Riley
Journal: PLoS Medicine (2010)

In light of the 2009 influenza pandemic and potential future pandemics, Maria Van Kerkhove and colleagues anticipate six public health challenges and the data needed to support sound public health decision making.
Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women
Authors: Graziana Lupattelli, Anna Maria Scarponi, Gaetano Vaudo, Donatella Siepi, Anna Rita Roscini, Fabio Gemelli, Matteo Pirro, Roberto A Latini, Helmut Sinzinger, Simona Marchesi, Elmo Mannarino
Journal: Metabolism (2004)
Determinants of Quality in Diabetes Care Process
Authors: Roberto Gnavi, Roberta Picariello, Ludmi la Karaghiosoff, Giuseppe Costa, Carlo Giorda
Journal: Diabetes Care (2009)

OBJECTIVE To investigate the role of clinical and socioeconomic variables as determinants of adherence to recommended diabetes care guidelines and assess differences in the process of care between diabetologists and general practitioners. RESEARCH DESIGN AND METHODS We identified diabetic residents in Torino, Italy, as of 31 July 2003, using multiple independent data sources. We collected data on several laboratory tests and specialist medical examinations registered during the subsequent 12 months and performed regression analyses to identify associations with quality-of-care indicators based on existing guidelines. RESULTS After 1 year, only 35.8% of patients had undergone a comprehensive assessment. In the multivariate models, factors independently and significantly associated with lower quality of care were age ≥75 years (prevalence rate ratio [PRR] 0.66 [95% CI 0.61–0.70]) and established cardiovascular disease (0.89 [0.86–0.93]). Disease severity (PRR for insulin-treated patients 1.45 [1.38–1.53]) and diabetologist consultation (PRR 3.34 [3.17–3.53]) were positively associated with high quality of care. No clear association emerged between sex and socioeconomic status. These differences were strongly reduced in patients receiving diabetologist care compared with patients receiving general practitioner care only. CONCLUSIONS Despite widespread availability of guidelines and simple screening procedures, a nonnegligible portion of the diabetic population, namely elderly individuals and patients with less severe forms of the disease, are not properly cared for. As practitioners in diabetes centers are more likely to adhere to guidelines than general practitioners, quality in the diabetes care process can be improved by increasing the intensity of disease management programs, with greater participation by general practitioners.
Aurora Kinase A Messenger RNA Overexpression Is Correlated with Tumor Progression and Shortened Survival in Head and Neck Squamous Cell Carcinoma
Authors: Rudolf Reiter, Peter Gais, Uta Jütting, Miriam K. Steuer-Vogt, Anja Pickhard, Karin Bink, Sandra Rauser, Silke Lassmann, Heinz Höfler, Martin Werner, Axel Walch
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Aurora kinase A (AURKA/STK15/BTAK) encodes a serine/threonine kinase associated with chromosomal distribution and its up-regulation induces chromosomal instability, thereby leading to aneuploidy and cell transformation in several types of cancer. In this study, we investigated the role of AURKA in head and neck squamous cell carcinoma (HNSCC). Experimental Design: The mRNA expression levels of AURKA were compared in tumor tissues of 66 HNSCC patients with those in corresponding normal squamous epithelium by real-time quantitative reverse transcriptase-PCR. In addition, the association between AURKA mRNA and protein expression, centrosome abnormalities, and aneuploidy was studied in a subset of cases (n = 34). All molecular variables were correlated to histomorphologic findings and clinical follow-up data of the patients. Results: AURKA mRNA up-regulation was significantly associated with tumor stage and the occurrence of regional lymph node, as well as distant metastasis (P &amp;lt; 0.0001 for all). Similarly, a correlation was found for protein expression and the occurrence of regional lymph node (P = 0.0183) and distant metastasis (P = 0.03). The mRNA was positively associated with protein expression (P = 0.003) and centrosome abnormalities (P = 0.03). Cox regression analysis revealed that AURKA mRNA up-regulation correlated with disease-free survival of the patients (P = 0.03) as well as shorter overall survival (P &amp;lt; 0.001). Conclusions: We conclude that the up-regulation of AURKA mRNA may play a critical role in the tumor progression of HNSCC and provides useful information as a prognostic factor for HNSCC patients.
Response to Letter Regarding Article, “Primary Angioplasty Versus Fibrinolysis in Acute Myocardial Infarction: Long-Term Follow-Up in the Danish Acute Myocardial Infarction 2 Trial”
Authors: Michael Maeng, Peter Haubjerg Nielsen, Martin Busk, Steen Dalby Kristensen, Torsten Toftegaard Nielsen, Henning Rud Andersen, Leif Spange Mortensen
Journal: Circulation (2010)
A Cineradiographic Study of the Snake Heart
Authors: KJELL JOHANSEN, RAGNAR HOL
Journal: Circulation Research (1960)

Cineradiographic studies on the cardiovascular system in snakes form the basis of this report. The method provides anatomical informations at the functional level and differs greatly from classical anatomical studies. The physiological interpretations involve timing of the various heart phases and the active role of the right atrium during ventricular filling. The snake ventricle has an incomplete septum and the admixture problem is discussed, as are also some considerations regarding the pulmonary circulation and the reserve mechanism of the snake heart.
Human tumor infiltrating lymphocytes cooperatively regulate prostate tumor growth in a humanized mouse model
Authors: Michael D Roth, Airi Harui
Journal: Journal for ImmunoTherapy of Cancer (2015)

The complex interactions that occur between human tumors, tumor infiltrating lymphocytes (TIL) and the systemic immune system are likely to define critical factors in the host response to cancer. While conventional animal models have identified an array of potential anti-tumor therapies, mouse models often fail to translate into effective human treatments. Our goal is to establish a humanized tumor model as a more effective pre-clinical platform for understanding and manipulating TIL.The immune system in NOD/SCID/IL-2Rγnull (NSG) mice was reconstituted by the co-administration of human peripheral blood lymphocytes (PBL) or subsets (CD4+ or CD8+) and autologous human dendritic cells (DC), and animals simultaneously challenged by implanting human prostate cancer cells (PC3 line). Tumor growth was evaluated over time and the phenotype of recovered splenocytes and TIL characterized by flow cytometry and immunohistochemistry (IHC). Serum levels of circulating cytokines and chemokines were also assessed.A tumor-bearing huPBL-NSG model was established in which human leukocytes reconstituted secondary lymphoid organs and promoted the accumulation of TIL. These TIL exhibited a unique phenotype when compared to splenocytes with a predominance of CD8+ T cells that exhibited increased expression of CD69, CD56, and an effector memory phenotype. TIL from huPBL-NSG animals closely matched the features of TIL recovered from primary human prostate cancers. Human cytokines were readily detectible in the serum and exhibited a different profile in animals implanted with PBL alone, tumor alone, and those reconstituted with both. Immune reconstitution slowed but could not eliminate tumor growth and this effect required the presence of CD4+ T cell help.Simultaneous implantation of human PBL, DC and tumor results in a huPBL-NSG model that recapitulates the development of human TIL and allows an assessment of tumor and immune system interaction that cannot be carried out in humans. Furthermore, the capacity to manipulate individual features and cell populations provides an opportunity for hypothesis testing and outcome monitoring in a humanized system that may be more relevant than conventional mouse models.
PTU-020 Rifaxamin is a highly efficacious treatment for the parkinsonian phenotype of hepatic encephalopathy (HE)
Authors: B Kok, M McPhail, M Foxton, D Shawcross
Journal: Gut (2012)

<h3>Introduction</h3> Patients who develop Parkinsonian symptoms on a background of cirrhosis and portosystemic shunting (PSS) form a unique subset of so-called acquired hepatocerebral degeneration. The syndrome is entirely different from acute HE and other forms of Parkinsonism that develop in patients without liver disease and rarely responds to standard treatments for HE. Rifaxamin is a non-absorbable antibiotic which has recently been shown to be efficacious in the secondary prevention of recurrent HE and is postulated to decrease gut ammonia production and/or bacterial translocation. <h3>Methods</h3> To prospectively evaluate the efficacy of rifaxamin 600 mg twice daily in three patients referred to the HE clinic at our institution with advanced cirrhosis, evidence of PSS and debilitating HE with extrapyramidal symptoms including resting tremor, bradykinesia, cog-wheel rigidity, drooling, loss of facial expression, shuffling gait and excessive somnolence. Each patient was evaluated independently by a hepatologist and a neurologist. Neuropsychological function testing (Trails A and B test), random venous ammonia (NH<sub>3</sub>), EEG and MRI brain/DaTscan were performed pre- and 4 weeks post rifaxamin. <h3>Results</h3> Patient 1 [male, age 61, α1AT, NH<sub>3</sub> 76 μmol/l] was unable to complete Trails A/B test at baseline. On rifaxamin his severe bradykinetic rigidity syndrome, drooling and leaning to one side on walking resolved. His repeat Trails B test was in 75–90<sup>th</sup> centile for a normal healthy age-matched population. His symptoms improved further on long acting dopamine therapy. Patient 2 [female, age 64, alcohol, abstinent, NH<sub>3</sub> 67 μmol/l] had an improved Trails A from the 10<sup>th</sup> to 50<sup>th</sup> centile, with resolution of bradykinesia, resting tremor and a dramatic reduction in her somnolence. Patient 3 [male, age 66, alcohol, abstinent, NH<sub>3</sub> 67 μmol/l] had remarkable improvement in his asymmetric bradykinetic rigid syndrome, regained his facial expression and was mobile with assistance whereas previously he had required hoisting. None of the patients had any improvement in their ammonia level or EEG with rifaximin despite resolution of symptoms. In the first two patients MRI brain post rifaxamin showed no change (high T1 signal in the globus pallidus) and in patient 3 a DaTscan post rifaxamin still showed decreased uptake in the right corpus striatum, in spite of dramatic clinical improvements. Patient 1 has now been transplanted and his extrapyramidal and neurocognitive symptoms have now resolved suggesting that this extrapyramidal syndrome is reversible. <h3>Conclusion</h3> Rifaxamin is efficacious in the treatment of the Parkinsonian phenotype of HE in this small case series which appears to be independent of ammonia lowering. Larger clinical trials are now warranted. <h3>Competing interests</h3> None declared.
Prevalence of BRCA1 and BRCA2 Gene Mutations in Patients With Early-Onset Breast Cancer
Authors: J. Peto, N. Collins, R. Barfoot, S. Seal, W. Warren, N. Rahman, D. F. Easton, C. Evans, J. Deacon, M. R. Stratton
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer. However, in an outbred population, the prevalence of BRCA1 and BRCA2 mutations in patients with breast cancer who were unselected for a family history of this disease has not been determined. METHODS: Mutations in the BRCA1 and BRCA2 genes were detected in blood samples from two population-based series of young patients with breast cancer from Britain. RESULTS: Mutations were detected in 15 (5.9%) of 254 women diagnosed with breast cancer before age 36 years (nine [3.5%] in BRCA1 and six [ 2.4%] in BRCA2) and in 15 (4.1%) of 363 women diagnosed from ages 36 through 45 years (seven [1.9%] in BRCA1 and eight [ 2.2%] in BRCA2). Eleven percent (six of 55) of patients with a first-degree relative who developed ovarian cancer or breast cancer by age 60 years were mutation carriers, compared with 45% (five of 11) of patients with two or more affected first- or second-degree relatives. The standardized incidence ratio for breast cancer in mothers and sisters was 365 (five observed and 1.37 expected) for 30 mutation carriers and 199 (64 observed and 32.13 expected) for 587 noncarriers. If we assume recent penetrance estimates, the respective proportions of BRCA1 and BRCA2 mutation carriers are 3.1% and 3.0%, respectively, of patients with breast cancer who are younger than age 50 years, 0.49% and 0.84% of patients with breast cancer who are age 50 years or older, and 0.11% and 0.12% of women in the general population. CONCLUSIONS: Mutations in the BRCA1 and BRCA2 genes make approximately equal contributions to early-onset breast cancer in Britain and account for a small proportion of the familial risk of breast cancer.
Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial
Authors: Marina Chiara Garassino, Olga Martelli, Massimo Broggini, Gabriella Farina, Silvio Veronese, Eliana Rulli, Filippo Bianchi, Anna Bettini, Flavia Longo, Luca Moscetti, Maurizio Tomirotti, Mirko Marabese, Monica Ganzinelli, Calogero Lauricella, Roberto Labianca, Irene Floriani, Giuseppe Giaccone, Valter Torri, Alberto Scanni, Silvia Marsoni
Journal: The Lancet Oncology (2013)