tbuckley/cabot-search huggingface dataset:
Absence of Lethal Reperfusion Injury After 3 Hours of Reperfusion
Authors: Doron Zahger, Juliana Yano, Aurelio Chaux, Michael C. Fishbein, William Ganz
Journal: Circulation (1995)

Background Whether reperfusion can cause necrosis of previously viable myocytes (lethal reperfusion injury) remains controversial. Numerous studies examined the ability of various agents to prevent or limit reperfusion injury, but the results were contradictory. In a single-canine-heart model of ischemia-reperfusion, we previously demonstrated that 5 minutes of reperfusion does not increase the transmural extent of necrosis. Since the 5-minute period of reperfusion is considered by some to be too short for the full manifestation of reperfusion injury, we reexamined the issue of lethal reperfusion injury using a modification of the single-heart model of ischemia-reperfusion that allowed extending the reperfusion period to 3 hours. Methods and Results In anesthetized, open-chest dogs, the distal half of the left anterior descending coronary artery (LAD) segment between the last diagonal branch and the apex was perfused via a shunt from the left carotid artery. The shunt was closed for periods of 90 to 180 minutes, depending on the ECG severity of ischemia, and reperfused for 3 hours. While the distal region was perfused from the carotid artery, the LAD was occluded proximal to the last diagonal branch for the same period of time as the distal region had been earlier. The time of occlusion was chosen such that the end of the occlusion period coincided with the end of the experiment. Thus, both regions of the LAD territory were subjected to identical periods of ischemia, but only the distal region was reperfused. At the end of the experiment, the boundary between the proximal (nonreperfused) and distal (reperfused) area was delineated by blue dye, and the heart was arrested, cut into slices 1 cm thick parallel to the LAD, and placed in triphenyltetrazolium chloride. The epicardial edges of necrosis in the reperfused and the nonreperfused regions were examined for any shift that might suggest a difference in the transmurality of necrosis. The areas of necrotic and viable myocardium were measured by planimetry within 1 cm on either side of the boundary. In all 14 dogs, the epicardial edges of necrosis ran as a single line across the boundary, and no shift was present. There was also no difference in the transmurality of necrosis between the reperfused and nonreperfused regions (64.9±20.7% versus 66.1±17.0% of left ventricular wall thickness, respectively; P =.32 by paired t test). Conclusions In a single-canine-heart model of ischemia-reperfusion, there was no evidence of lethal reperfusion injury after 3 hours of reperfusion.
Possible hazard to contact lens manufacture.
Authors: R Routledge
Journal: BMJ (1973)

JouRNAL 24 EBRuAY 1973 48 bacilli are not quite as rare as people might imagine.With a relatively low level of immunization among those most at risk, the appear- ance of a highly virulent strain could again give rise to an outbreak, the first few cases of which might well be diagnosed at necropsy.Until we know the precise reasons for the decline of diphtheria in the United Kingdom we should be cautious of writing its obituary.-Weare, etc.,
Saccharin and Cancer
Authors: George R. Meneely
Journal: JAMA (1979)

<h3>To the Editor.—</h3> I have read with growing fascination the exchange of views on the possible carcinogenicity of saccharin, both in formal scientific papers and most recently in the LETTERS section ofThe Journal(241:996, 1979). Here we have some sort of an epidemiologic Heisenberg principle: the more closely the possible carcinogenicity of saccharin is examined, the more the procedure of observation seems to affect the phenomenon that is to be observed, if not, indeed, the observers themselves. What makes the whole matter so fascinating is that it was not, repeat not, saccharin that was fed to those rats but sodium saccharin, and sodium at these levels is toxic for rats. Inadequate attention appears to have been addressed to such well-known toxic properties of sodium as production of hypertension, causation of increased renal and urinary bladder stones, and causation of great increases in water consumption and urine production, and to
Lung disease induced by drug addiction.
Authors: M. Slade, K. Burgess
Journal: Thorax (1996)

Lung disease induced by drug addictionIn their editorial on the pulmonary con- sequences ofillicit drug use (November 1995; 50:1125-7) Benson and Bentley draw at- tention to barotrauma as a complication of cocaine inhalation.Pneumothorax, pneumomediastinum, and pneumopericardium have also been described, however, in association with the use of marijuana,12 a drug that is more widely used in England and Australia than cocaine.The mechanism of injury is thought to be by coughing while breath- holding in inspiration, or by performance of a Valsalva manoeuvre.The latter has been recognised as a cause of spontaneous pneumo- mediastinum since the 17th century.3We have found it rewarding to seek a history of illicit drug use in young adult patients presenting with spontaneous pneumothorax.
The Education and Training of Future Physicians
Authors: Rodrigo B. Cavalcanti, Allan S. Detsky
Journal: JAMA (2011)

A PHYSICIAN MUST BE ABLE TO DIAGNOSE AND TREAT patients. The clinical skills required to be successful include gathering data, differentiating important from unimportant facts, making decisions about further investigations and treatments, implementing therapy, and providing follow-up, education, and counseling. These skills cannot be learned through reading or in classrooms alone; practical experience is required. The present method of exposing physicians-intraining to practical experience involves a hierarchical team approach with graded levels of responsibility whereby the decisions of the most junior members of the team are reviewed by physicians with more experience and seniority. These practical experiences impart content knowledge and also allow trainees to become comfortable with decision making and to learn the consequences of these decisions. Although there may be better ways to train future physicians, this apprenticeship method seems to work, as evidenced by the relatively low failure rate in medical schools and training programs. Part of the apprenticeship experience also includes having members at higher levels of the hierarchy evaluate those at lower levels. As such, the supervising individuals are both coaches (instructing and assisting trainees in improving their clinical skills) and judges (responsible for performance assessment of the same trainees). In this Commentary we discuss some of the problems created by this dual role and offer potential solutions.
Locally Advanced Head and Neck Squamous Cell Carcinomas Treated with DCF (Docetaxel,Cisplatin,5-FU) Induction Chemotherapy
Authors: J. Taguchi, T. Amano, I. Kinoshita, R. Honma, Y. Shimizu, K. Tsuchiya, H. Shirato, A. Homma, S. Fukuda, H. Akita
Journal: Annals of Oncology (2013)
Surgeon from Mid Staffordshire is first to face GMC hearing over performance
Authors: C. Dyer
Journal: BMJ (2014)

A consultant surgeon at Mid Staffordshire NHS Foundation Trust is facing allegations of inadequate professional performance at the Medical Practitioners Tribunal Service.

The trust was found to have multiple failings in two inquiries chaired by Robert Francis QC, but Raafat Gendy is the only doctor to face a hearing on charges from the General Medical Council over his performance.

Cases were dropped against four doctors in management …
Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21
Authors: Xue Jun Zhang, Wei Huang, Sen Yang, Liang Dan Sun, Feng Yu Zhang, Qi Xing Zhu, Fu Ren Zhang, Chi Zhang, Wen Hui Du, Xiong Ming Pu, Hui Li, Feng Li Xiao, Zai Xing Wang, Yong Cui, Fei Hao, Jie Zheng, Xue Qin Yang, Hui Cheng, Chun Di He, Xiao Ming Liu, Li Min Xu, Hou Feng Zheng, Shu Mei Zhang, Jian Zhong Zhang, Hong Yan Wang, Yi Lin Cheng, Bi Hua Ji, Qiao Yun Fang, Yu Zhen Li, Fu Sheng Zhou, Jian Wen Han, Cheng Quan, Bin Chen, Jun Lin Liu, Da Lin, Li Fan, An Ping Zhang, Sheng Xiu Liu, Chun Jun Yang, Pei Guang Wang, Wen Ming Zhou, Guo Shu Lin, Wei Dong Wu, Xing Fan, Min Gao, Bao Qi Yang, Wen Sheng Lu, Zheng Zhang, Kun Ju Zhu, Song Ke Shen, Min Li, Xiao Yan Zhang, Ting Ting Cao, Wei Ren, Xin Zhang, Jun He, Xian Fa Tang, Shun Lu, Jian Qiang Yang, Lin Zhang, Dan Ni Wang, Feng Yuan, Xianyong Yin, Hong Jie Huang, Hai Feng Wang, Xin Yi Lin, Jian Jun Liu
Journal: Nature Genetics (2009)
Ethylene Dibromide Poisoning
Authors: Richard S. Jacobs
Journal: JAMA (1985)

To the Editor.—  I have recently read the fine article by Letz et al 1 on two fatalities occurring as the result of occupational exposure to the fumigant ethylene dibromide. Not only is the article interesting, it is accurate, which I know since our Poison Control Center was immediately contacted after the exposure occurred. During the initial conversation with the base hospital handling the call, it was quite evident there was considerable confusion at the scene of the poisoning regarding the material to which the men were exposed and the initial approach to their management.  Assuming the worst possible situation, information was provided by our Poison Control Center concerning the toxic effects and management of ethylene dibromide exposure. Recognizing (as clearly pointed out by Dr Letz) that there are no known effective antidotes for ethylene dibromide poisoning, strong admonitions were given to ensure that all unnecessary personnel on the scene
THE MANAGEMENT OF EARLY ABORTIONS.
Authors: S. L. JEPSON
Journal: JAMA (1894)

This subject is rendered interesting by reason of the frequency of the occurrence of early abortions, and by the unfortunate consequences so very often resulting, it being a well-recognized fact that a large number of the cases of uterine disease to which women are subject can be directly traced to prior abortions. That by a proper management of these cases many evil results can be prevented, all will admit, and hence exists the necessity of scientific treatment, with the cultivation of some patience, for, as in all forms of pelvic disease in women, there is too great a tendency to speedily resort to surgical methods, the physician not placing sufficient reliance in nature aided by wise, conservative therapeutic measures. Several years since, in this city, a physician just returned from a course of post-graduate instruction in New York, was preparing a table upon which to place a patient to remove the
Impaired responses of peripheral blood mononuclear cells to T-cell stimulants in alopecia areata patients with a poor response to topical immunotherapy
Authors: T. Yoshino, H. Asada, Y. Ando, H. Fujii, Y. Yamaguchi, K. Yoshikawa, S. Itami
Journal: British Journal of Dermatology (2001)

Topical immunotherapy with a contact allergen is effective in alopecia areata (AA). However, the mechanism of the effect is still unknown, and pretreatment prediction of the outcome of therapy in each patient remains difficult.To predict the clinical effect of this therapy in AA patients, we investigated the relationship between clinical responses to topical immunotherapy and in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to T-cell stimulants.PBMC were taken from 67 AA patients before or during diphenylcyclopropenone immunotherapy and from 14 healthy controls, and proliferative responses to phytohaemagglutinin and staphylococcal enterotoxin B were evaluated by measuring [3H]-thymidine incorporation.PBMC from the AA patients with a good clinical response to immunotherapy showed a normal level of proliferation, whereas PBMC from the poor responders showed a markedly suppressed proliferative response and interleukin (IL)-2 production, but increased IL-4 production compared with the controls.The proliferative response of PBMC to T-cell stimulants may be one of the indicators of the clinical effect of topical immunotherapy for AA.
It takes a village: a comparative study of maternity waiting homes in rural Liberia
Authors: Jody R Lori, Garfee Williams, Michelle L Munro, Nene Diallo, Carol J Boyd
Journal: The Lancet Global Health (2014)

BackgroundAlthough evidence is insufficient to determine the effectiveness of maternity waiting homes on improvement of maternal and newborn health, several countries have identified success in institutionalisation of maternity waiting homes as a way to reduce maternal and neonatal deaths by increasing access to skilled birth attendants. We examined maternity waiting homes as an intervention to decrease maternal and neonatal morbidity and mortality in Liberia, west Africa.MethodsWith a matched cohort design in remote, rural Liberia, five primary health-care facilities with new maternity waiting homes (exposed intervention group) were matched to five facilities without maternity waiting homes (unexposed comparison group). All 10 clinics have 24-h staffing and are overseen by Africare-Liberia. We collected data for team births (skilled birth attendants and traditional midwives working together during delivery) from December, 2010, to August, 2012 and data for maternal deaths from March, 2011, to September, 2012. We used a logistic regression model with generalised estimating equations to evaluate differences from baseline (Dec 1, 2010– Feb 28, 2011) to postintervention (June 1, 2012–Aug 31, 2012).FindingsThe proportion of team births significantly increased in communities with maternity waiting homes from 18 (10·80%) of 166 (95% CI 0·03–0·32) to 248 (95·20%) of 248 (0·73–0·99, p<0·001), whereas in communities without maternity waiting homes the team births increased from 40 (20·50%) of 195 (0·04–0·63) to 178 (69·80%) of 255 (0·20–0·96, p=0·065). Team births increased more rapidly in MWH communities (Wald's c2=3·75, df=1, p=0·053). Maternal deaths significantly differed between communities with maternity waiting homes (n=3) and communities without maternity waiting homes (n=12; Wald's c2=4·22, df=1, p=0·040).InterpretationOur findings add to the evidence of the potential benefit and effectiveness of maternity waiting homes.FundingUS Agency for International Development & Fogarty International, National Institutes of Health.
Follow up study of labial salivary gland lesions in primary Sjogren's syndrome.
Authors: J P Leroy, Y L Pennec, C Soulier, J M Berthelot, G Letoux, P Youinou
Journal: Annals of the Rheumatic Diseases (1992)

Labial salivary gland biopsy samples were taken from 27 patients with primary Sjögren's syndrome (SS), 10 with rheumatoid arthritis (RA) and secondary SS, and four normal control subjects on two occasions at intervals of more than one year. In the former group of patients, eight of the nine initially negative analyses were positive on the second sample, whereas two of the seven patients with RA and secondary SS were negative for the first sample and then positive for the second. In primary SS, the mean (SD) variation of the focus score was 1.7 (2.6) and that of salivary duct infiltration 0.2 (0.7). The former correlated well with the latter.
Role of Extracellular Signal-Regulated Kinases in Angiotensin II–Stimulated Contraction of Smooth Muscle Cells From Human Resistance Arteries
Authors: Rhian M. Touyz, Gang He, Li-Yuan Deng, Ernesto L. Schiffrin
Journal: Circulation (1999)

Background —We assessed the role of extracellular signal–regulated kinases (ERKs) in Ang II–stimulated contraction and associated signaling pathways in vascular smooth muscle cells (VSMCs) from human small arteries. Methods and Results —VSMCs derived from resistance arteries (&lt;300 μm in diameter) from subcutaneous gluteal biopsies of healthy subjects (n=8) were used to assess Ang II–stimulated [Ca 2+ ] i , pH i , and contractile responses. [Ca 2+ ] i and pH i were measured with fura 2- AM and BCECF-AM, respectively, and contraction was measured photomicroscopically in cells grown on Matrigel matrix. To determine whether tyrosine kinases and ERKs influence Ang II–stimulated responses, cells were pretreated with 10 −5 mol/L tyrphostin A-23 (tyrosine kinase inhibitor) and PD98059 (MEK inhibitor). Ang II–stimulated MEK activity was determined by tyrosine phosphorylation of ERKs. The angiotensin receptor subtypes (AT 1 and AT 2 ) were assessed with [Sar 1 ,Ile 8 ]Ang II (a nonselective subtype antagonist), losartan (a selective AT 1 antagonist), and PD123319 (a selective AT 2 antagonist). Ang II dose-dependently increased [Ca 2+ ] i (pD 2 =8.4±0.36, E max =541±55 nmol/L), pH i (pD 2 =9.4±0.29, E max =7.19±0.01), and contraction (pD 2 =9.2±0.21, E max =36±2.2%). Ang II induced rapid tyrosine phosphorylation of ERKs, which was inhibited by PD98059. Tyrphostin A-23 and PD98059 attenuated ( P &lt;0.05) Ang II–stimulated second messengers, and PD98059 reduced Ang II–induced contraction by &gt;50%. [Sar 1 ,Ile 8 ]Ang II and losartan, but not PD123319, blocked Ang II–stimulated responses. Conclusions —These data demonstrate that in VSMCs from human peripheral resistance arteries, functional Ang II receptors of the AT 1 subtype are coupled to signaling cascades involving Ca 2+ and pH i pathways that are partially dependent on tyrosine kinases and ERKs. ERKs, the signaling cascades characteristically associated with cell growth, may play an important role in Ang II–stimulated contraction of human VSMCs.
804. In Vivo Correction of a Metabolic Liver Disease by AAV8-Mediated Homologous Recombination
Authors: Karsten Wursthorn, Terry Storm, Mark A. Kay, Milton Finegold, Markus Grompe
Journal: Molecular Therapy (2006)

Top of pageAbstract
AAV-8 is currently the most efficient serotype to transduce hepatocytes and establish long-lasting transgene expression. However, most vectors remain episomal, integration events are rare and occur randomly. In our study we aimed to prove that targeted integration and homologous recombination by AAV is a feasible method for gene correction in vivo. We therefore used the Fah5961SB mouse model carrying a single bp splice-site mutation causing loss of an exon in the fumarylacetoacetate hydrolase (Fah) gene. Fah mutant mice are a model of the human disease hereditary tyrosinemia type 1 and develop progressive liver failure when the protective drug NTBC is withdrawn. An AAV-8 vector was constructed containing 4.5 kb of the wild-type genomic sequence 5 and 3 of the splice mutation. Importantly, this vector does not contain a Fah expression cassette, but can restore Fah expression only after homologous recombination with the mutant genome. Neonatal (n=6, day of birth, 2x10^11 copies/mouse, intraperitoneal-ip), newborn (n=6, 4 days old, 1x10^11 copies/mouse, ip) and adult mice (n=8, 1x10^11 copies/mouse, portal vein) of both sexes were injected. Corrected hepatocytes were selected in vivo by NTBC withdrawal. Neonatal mice injected at the day of birth showed stabilization or increase of weight at the end of the first cycle of NTBC withdrawal (25 days). Multiple macroscopicallly visible nodules of healthy hepatic tissue were seen when the liver was harvested and histological analysis confirmed Fah+ nodules and thus gene correction at high frequency. Newborns injected at age 4 days and adult mice also showed flattening of weight loss after 25 days off NTBC. Histological analysis in these older mice also showed Fah-positive nodules providing evidence of correction of the point mutation. Further histological and genomic analysis to ascertain the precise quantity and time course of integration events are pending. Our experiments show for the first time in vivo that gene correction by homologous recombination with AAV-8 is possible at reasonable frequencies. Combined with in vivo selection this resulted in complete clinical restoration of an otherwise lethal metabolic liver disease.
Researchers discover "feedback loop" in allergic reactions
Authors: S Gottlieb
Journal: BMJ (1999)

Researchers testing an experimental antiallergy drug think that they have discovered a new immunological feedback loop that is involved in the basic mechanism driving allergic reactions (Journal of Immunology 1999;162:5183-90).

The new biochemical loop links the amount of IgE antibody to the number of immune cell IgE receptors scattered on preformed immunological mediators such as those found in mast cells. …
Sports or statins for atheroprotection? New insight from Kruppel-like factor 2
Authors: T THUM, J BAUERSACHS
Journal: Cardiovascular Research (2006)

See article by van Thienen et al. \[6\] (pages 231–240) in this issue .

Nitric oxide (NO) plays a central role in the control of vascular homeostasis. Adequate NO production stimulated by continuous laminar flow on the endothelial surface, so-called shear stress, prevents endothelial inflammation and development of endothelial dysfunction. Recently, a novel class of mechanosensitive transcription factors has been identified that in endothelial cells transfer shear stress to various downstream targets such as the endothelial NO synthase (eNOS) [1]. These Kruppel-like factors (KLFs) are zinc finger transcription factors that act as transcriptional activators or suppressors upon binding to a CACCC promoter/enhancer element. A total of 16 KLF family members have been identified thus far, but only some are expressed in vascular cells, including KLF2 (reviewed in [2]). In the past, KLF2 was identified as a regulator of T cell differentiation and activation [3]. Recently, shear stress was shown to affect endothelial KLF2 expression with up-regulation by laminar and repression by perturbed flow [4]. KLF2 induces eNOS expression, thereby contributing to the regulation of vascular tone [1]. Interestingly, the up-regulation of eNOS by 3-hydroxy-3-methylglutaryl coenzyme A … 

*Corresponding author. Medizinische Klinik und Poliklinik I, Kardiologie Universitatsklinikum, Bayerische Julius-Maximilians-Universitat Josef-Schneider Str. 2 97080 Wurzburg Germany. Tel.: +49 931 201 36455; fax: +49 931 201 36664. Email address: Thum_T{at}klinik.uni-wuerzburg.de
Severe bronchospasm associated with rituximab for refractory Churg–Strauss syndrome
Authors: M-A Bouldouyre, P Cohen, L Guillevin
Journal: Annals of the Rheumatic Diseases (2009)

Rituximab is now used to control antineutrophil cytoplasm antibody (ANCA)-associated vasculitides, eg, Wegener’s granulomatosis.1 2 In Churg–Strauss syndrome (CSS), a small-vessel systemic vasculitis with asthma and eosinophilia, 39% of patients have ANCA.3 4 Rituximab could be effective in ANCA-associated vasculitides, even if ANCA are not present at the time of prescription, because B lymphocytes also play a role as antigen-presenting cells and can modulate the immune response in another way than targeting antibody production. Therapy-refractory CSS5 was successfully treated with rituximab in three patients.6–8 We would like to draw attention to the potential risk of rituximab-associated bronchospasm, by reporting …
Improved quality of life (QoL) among seasonal allergic rhinitis (SAR) patients treated with olopatadine HCl nasal spray, 0.4% and olopatadine HCl nasal spray, 0.6% compared to vehicle*1
Authors: F.C. Hampel, P.H. Ratner, N.J. Amar, J.H. van Bavel, D. Mohar, K. Venkataraman, G.M. Wall, M. Brubaker, M. Drake, K. Crenshaw
Journal: Journal of Allergy and Clinical Immunology (2004)