tbuckley/cabot-search huggingface dataset:
Long-term hazards of Thorotrast.
Authors: J. T. Boyd, A. O. Langlands, J. J. Maccabe
Journal: BMJ (1968)

Necropsy on the first heart transplantation in man confirmed that death was due to extensive bilateral pneumonia and not to rejection of the heart.Signs of rejection, however, were demon- strated histologically, but were of a low order compared with those seen in the transplanted dog heart.How far the mildness of the rejection signs is to be ascribed to species differences, immunosuppressive drugs and procedures, postoperative rest, and nursing and medical care, or to the good matching of leucocyte antigens cannot at the moment be assessed.
The Pathophysiology and Treatment of Glaucoma
Authors: Robert N. Weinreb, Tin Aung, Felipe A. Medeiros
Journal: JAMA (2014)

Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition.To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma.A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians.The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression.Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.
Interstitial fluid concentrations of glycerol, glucose, and amino acids in human quadricep muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle.
Authors: D G Maggs, R Jacob, F Rife, R Lange, P Leone, M J During, W V Tamborlane, R S Sherwin
Journal: Journal of Clinical Investigation (1995)

To determine the relationship between circulating metabolic fuels and their local concentrations in peripheral tissues we measured glycerol, glucose, and amino acids by microdialysis in muscle and adipose interstitium of 10 fasted, nonobese human subjects during (a) baseline, (b) euglycemic hyperinsulinemia (3 mU/kg per min for 3 h) and, (c) local norepinephrine reuptake blockade (NOR). At baseline, interstitial glycerol was strikingly higher (P < 0.0001) in muscle (3710 microM) and adipose tissue (2760 microM) compared with plasma (87 microM), whereas interstitial glucose (muscle 3.3, fat 3.6 mM) was lower (P < 0.01) than plasma levels (4.8 mM). Taurine, glutamine, and alanine levels were higher in muscle than in adipose or plasma (P < 0.05). Euglycemic hyperinsulinemia did not affect interstitial glucose, but induced a fall in plasma glycerol and amino acids paralleled by similar changes in the interstitium of both tissues. Local NOR provoked a fivefold increase in glycerol (P < 0.001) and twofold increase in norepinephrine (P < 0.01) in both muscle and adipose tissues. To conclude, interstitial substrate levels in human skeletal muscle and adipose tissue differ substantially from those in the circulation and this disparity is most pronounced for glycerol which is raised in muscle as well as adipose tissue. In muscle, insulin suppressed and NOR increased interstitial glycerol concentrations. Our data suggest unexpectedly high rates of intramuscular lipolysis in humans that may play an important role in fuel metabolism.
Retinoids, bile acids and PPARs in Barrett's oesophagus
Authors: A. De Gottardi, A. Hadengue, J.-M. Dumonceau
Journal: Gut (2007)

Intestinal metaplasia of the oesophagus (Barrett’s oesophagus) is the most important risk factor for oesophageal adenocarcinoma. Although the role of mixed bile and acid gastro-oesophageal reflux is well established, the contribution of nuclear receptor signalling in the pathogenesis of Barrett’s oesophagus remains largely unknown. The recent article by Chang et al. ( Gut 2007; 56 :906–17) showing that retinoic acid and lithocholic acid play an important role in the development of oesophageal intestinal metaplasia, is of particular interest, because retinoid receptors are also heterodimeric partners of multiple nuclear receptors.

We recently published a report demonstrating the over-expression of the …
Human IgE Synthesis <i>in vitro</i>
Authors: J. M. Knutti‐Müller, B. M. Stadler, C. M. Magnusson, L. De Weck
Journal: Allergy (1986)

Using monoclonal anti‐human IgE antibodies recognizing the Dɛ1 or Dɛ2 epitope, we have developed a sandwich radioimmunoassay (RIA) to determine IgE in human cell cultures. With the help of this assay, various methods of measuring an actual de novo IgE synthesis were compared. It was necessary to substract preformed IgE from released IgE in the culture supernatant and the IgE associated to the cultured cells, in order to determine a net IgE synthesis which would reflect de novo synthesized IgE. Using this differential in vitro IgE assessment, no net IgE synthesis could be demonstrated in culture conditions which lead to strong IgG synthesis. Actual net in vitro IgE antibody production was only found in approximatively 30% of cell cultures from atopic donors. This spontaneous IgE synthesis did not correlate to the serum IgE levels of the patients. However, correlations were found between serum IgE levels and amount of preformed, released or cell‐associated IgE of the cultures.
Women doctors in urban general practice: the doctors.
Authors: M Cooke, C Ronalds
Journal: BMJ (1985)

A large study of general practitioners in Manchester showed that women doctors were younger than men doctors, and few were single handed or worked in deprived inner city areas. They had closely similar patterns of care to their male colleagues, and although they worked slightly fewer hours in surgery, they had almost identical consultation times per patient. Women general practitioners were less active in politics and education than men.
Functional Asplenia and Portal Hypertension in a Patient with Primary Splenic Hemangiosarcoma
Authors: A EFTAL Y??CEL, HAT??CE DURAK, ??REM BERNAY, YUSUF BAYRAKTAR, COSKUN BEKDIK, HASAN TELATAR
Journal: Clinical Nuclear Medicine (1990)

A 60-year-old man with primary splenic hemangiosarcoma (PSH) presented with weakness, weight loss, abdominal pain, and anemia. Physical examination reveaied hepatomegaly, ascites, and firm, huge splenomegaly. Ultrasonography showed many nodular structures characterized by hypoechogenic and hyperechogenic areas. The patient also had portal hypertension, which was confirmed by physical findings and by measurement of portal vein pressure during operation. A liver-spleen scan using Tc-99m sulfur colloid and Tc-99m labeled heat denatured erythrocytes failed to demonstrate any splenic uptake, a reliable feature of functional asplenia. Although on a total body scan with Ga-67 citrate there was no splenic uptake, there was gallium uptake in the liver, where the presence of the metastatic lesion was histopathologically verified and confirmed by operation. There was also uptake in the middle zones of the lungs. Ga-67 citrate imaging appears to be helpful in the diagnosis of metastasis of PSH, and PSH can rarely cause portal hypertension.
Inactivation of DNA-Dependent Protein Kinase Leads to Spindle Disruption and Mitotic Catastrophe with Attenuated Checkpoint Protein 2 Phosphorylation in Response to DNA Damage
Authors: Zeng-Fu Shang, Bo Huang, Qin-Zhi Xu, Shi-Meng Zhang, Rong Fan, Xiao-Dan Liu, Yu Wang, Ping-Kun Zhou
Journal: Cancer Research (2010)

Abstract DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is well known as a critical component involving the nonhomologous end joining pathway of DNA double-strand breaks repair. Here, we showed another important role of DNA-PKcs in stabilizing spindle formation and preventing mitotic catastrophe in response to DNA damage. Inactivation of DNA-PKcs by small interfering RNA or specific inhibitor NU7026 resulted in an increased outcome of polyploidy after 2-Gy or 4-Gy irradiation. Simultaneously, a high incidence of multinucleated cells and multipolar spindles was detected in DNA-PKcs-deficient cells. Time-lapse video microscopy revealed that depression of DNA-PKcs results in mitotic catastrophe associated with mitotic progression failure in response to DNA damage. Moreover, DNA-PKcs inhibition led to a prolonged G2-M arrest and increased the outcome of aberrant spindles and mitotic catastrophe in Ataxia-telangiectasia mutated kinase (ATM)–deficient AT5BIVA cells. We have also revealed the localizations of phosphorylated DNA-PKcs/T2609 at the centrosomes, kinetochores, and midbody during mitosis. We have found that the association of DNA-PKcs and checkpoint kinase 2 (Chk2) is driven by Ku70/80 heterodimer. Inactivation of DNA-PKcs strikingly attenuated the ionizing radiation–induced phosphorylation of Chk2/T68 in both ATM-efficient and ATM-deficient cells. Chk2/p-T68 was also shown to localize at the centrosomes and midbody. These results reveal an important role of DNA-PKcs on stabilizing spindle formation and preventing mitotic catastrophe in response to DNA damage and provide another prospect for understanding the mechanism coupling DNA repair and the regulation of mitotic progression. Cancer Res; 70(9); 3657–66. ©2010 AACR.
472 THE TRIPLEHELICAL PEPTIDE (GPO)10 INTERACTS WITH THE CBD OF MMP-2 RESULTING IN A DIMINISHED BINDING OF MMP-2 TO FIBRILLAR LIVER COLLAGENS AND ENHANCED MATRIX DEGRADATION
Authors: C.H. Freise, M. Ruehl, U. Erben, M. Seja, R. Farndale, M. Zeitz, R. Somasundaram
Journal: Journal of Hepatology (2008)
Obstetrics in Brecon
Authors: P J Snow, K J P Price, P O Faulkner, R L Coppock, J A J Davies
Journal: BMJ (1979)

Vaccine strategies targeting the earliest stages of HIV infection at the mucosal portal of entry may prevent acquisition. Thus, understanding the immune profiles of mucosal cells after immunization is important for vaccine design. We vaccinated rhesus macaques with replicating Ad5hr-SIV<i>env/gag/nef</i> or empty Ad5hr vector orally/intranasally and intra-tracheally, followed by intramuscular gp120 boosts in alum or alum only. Macaques were repeatedly challenged intravaginally with low doses of SIV<sub>mac251</sub>. We evaluated cervicovaginal macrophage (CM) responses to Ad5hr 3d post-immunization, and alveolar macrophage (AM) responses in BAL, as initial immunization was to the upper respiratory tract. CM showed significantly increased expression of the chemokines CCL3 (p&lt;0.01), CCL4, CCL5 and CXCL8 (p&lt;0.0001 for all) after the first prime, which decreased post-2<sup>nd</sup> boost. CD4<sup>+</sup> T-cell frequency in the cervical mucosa was unchanged. CD16 expression was significantly increased post 2<sup>nd</sup> Ad and positively correlated with the number of challenges needed for infection (r=0.6763; p=0.0051). Immunization also increased expression of CD16 on AMs up to the 1<sup>st</sup> boost time point. Activation of AMs was evident by increased expression of CD40 and CD80 post-2<sup>nd</sup> Ad compared to naïve macaques. APRIL expression also significantly increased post-2<sup>nd</sup> Ad compared to naive levels and correlated with B cell frequency in BAL (r=0.7329; p=0.0019) and total IgG in BAL-Fluid (r=0.525; p=0.0471). These data indicate that the vaccine regimen did not induce recruitment of susceptible cells to the vaginal mucosa but increased CM CD16 expression associated with delayed SIV acquisition, and further induced AM cytokine expression that may be associated with B cell help.
Thymidylate Synthase Expression in Hepatic Tumors Is a Predictor of Survival and Progression in Patients With Resectable Metastatic Colorectal Cancer
Authors: Mithat Gonen, Amanda Hummer, Alice Zervoudakis, Deidre Sullivan, Yuman Fong, Debabrata Banerjee, David Klimstra, Carlos Cordon-Cardo, Joseph Bertino, Nancy Kemeny
Journal: Journal of Clinical Oncology (2003)

To investigate the role of thymidylate synthase (TS),p53, and epidermal growth factor receptor (EGF-R) expressions in hepatic tumors in predicting overall survival (OS), progression-free survival (PFS), and hepatic progression-free survival (HPFS) in patients with resectable metastatic colorectal cancer who were randomly assigned to receive either systemic chemotherapy (SYS) alone or systemic and hepatic arterial infusion (HAI+SYS) chemotherapy following liver surgery.Tissues from metastatic tumors were collected during liver resection from 156 patients, and marker expressions were determined using immunohistochemistry on frozen samples. Univariate associations between marker expressions and baseline variables with OS, PFS, and HPFS were examined. Independent predictors of outcome were determined using a multivariate Cox model.In multivariate analyses, TS overexpression was found to be an independent factor of poor prognosis in OS (P <.01), PFS (P =.06), and HPFS (P <.01). In addition, resection margin was a significant independent factor for all three outcomes. Patients who received HAI+SYS experienced delayed progression in general, and in the liver, specifically. Increased levels of serum alkaline phosphatase correlated with hepatic progression. We also found a significant TS-treatment interaction for OS (P =.01) in multivariate analysis. In particular, TS+ patients receiving HAI+SYS had significantly higher survival than those receiving SYS (64 month sv 21 months; P =.01).TS levels in hepatic tumors and resection margin are independent predictors of survival and progression in patients with metastatic colorectal cancer, whereas p53 and EGFR are not independent predictors. Treatment with HAI + SYS significantly improved the survival profile of TS+ patients.
Golli Protein Negatively Regulates Store Depletion-Induced Calcium Influx in T Cells
Authors: Ji-Ming Feng, Yanhong K. Hu, Lai-Hua Xie, Christopher S. Colwell, Xuesi M. Shao, Xiao-Ping Sun, Boming Chen, Hezhen Tang, Anthony T. Campagnoni
Journal: Immunity (2006)
Gene–Environment Interactions and the Etiology of Common Complex Disease
Authors: Richard S. Cooper
Journal: Annals of Internal Medicine (2003)

Genetic epidemiology has greatly expanded its scope as a result of major technological innovations in the past decade. Laboratory capacity to determine DNA variation and archival information on the human genome sequence are now readily available. A wide range of research projects have been launched on chronic disease and health problems of aging, on the assumption that a better understanding of mechanisms will improve treatment and prevention. In many instances, the actions of genes are known to be modified by environmental conditions, and considerable emphasis has now been placed on finding specific interactions between genes and the environment. Studies in agriculture and animals provide clear empirical evidence on the importance of this concept. Describing gene–environment interactions in studies of humans is still very challenging, however, given the difficulties in study design and measurement. Despite the theoretical value of characterizing both intrinsic and extrinsic components of the causal process in the development of disease, the argument can also be made that main effects of each component separately are much more important. For these reasons, gene–environment interactions are likely to remain a conceptual framework for health research rather than a practical goal for the foreseeable future.
A regulated delivery system for inner ear drug application
Authors: Shayanne A. Lajud, Zhao Han, Fang-Lu Chi, Rende Gu, Danish A. Nagda, Orysia Bezpalko, Samudra Sanyal, Andres Bur, Ziying Han, Bert W. O'Malley, Daqing Li
Journal: Journal of Controlled Release (2013)
The electrocardiogram in epidemiologic investigations. A new classification system.
Authors: H V Pipberger, E Simonson, E A Lopez, M A Araoye, H A Pipberger
Journal: Circulation (1982)

A new coding system for ECG abnormalities was developed, based on Frank's orthogonal ECG leads. In contrast to other systems, such as the Minnesota Code (MC), the new system was based on data collected prospectively in a cooperative study of 5031 records. The records were classified solely on the basis of non-ECG information. A record sample from normal women was also available. The large data base allowed stratification of ECG criteria according to sex and race. ECG criteria were determined at two levels of sensitivity and specificity. Specificity was 80-100% at the first level and 90-90% at the second. The new system has fewer criteria than other codes, which leads to reduction of coding errors and coding time. For common problems in differential diagnosis, optional criteria were included. A computer program for automated coding was also developed.
Serum PARC/CCL-18 Concentrations and Health Outcomes in Chronic Obstructive Pulmonary Disease
Authors: Don D. Sin, Bruce E. Miller, Annelyse Duvoix, S. F. Paul Man, Xuekui Zhang, Edwin K. Silverman, John E. Connett, Nicholas A. Anthonisen, Robert A. Wise, Donald Tashkin, Bartolome R. Celli, Lisa D. Edwards, Nicholas Locantore, William MacNee, Ruth Tal-Singer, David A. Lomas
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum.Objectives: To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality.Methods: PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study.Measurements and Main Results: Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort.Conclusions: Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD.Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).
Self-prescribing: III-Advised?-Reply
Authors: Patrick H. Hughes
Journal: JAMA (1992)

<h3>In Reply.</h3> —Dr Tiefenbrunn's letter expresses a legitimate point of view. In our recent survey of state self-treatment guidelines, the state of Missouri medical licensing board reported that they do have guidelines discouraging physician self-treatment with controlled prescription drugs. These restrictions apply to "a pattern of personal use or consumption of any controlled substance unless it is prescribed, dispensed, or administered by another physician who is authorized by law to do so" (Healing Arts Practice Act, Chapter 334.100[22], RSMo). Tiefenbrunn's point of view is understandable for the majority of physicians who either do not self-treat with controlled prescription drugs, or do so infrequently and with prudence. It is understandable for such physicians to assert their right to self-treat, because they believe they are at no risk from occasional self-medication for legitimate medical conditions. But what of those physicians who are vulnerable to misusing or becoming dependent on controlled prescription drugs?
Conventional Coronary Care Unit Monitoring
Authors: Joseph Lindsay
Journal: JAMA (1975)

Conventional electrocardiographic monitoring techniques depend on human observation of an oscilloscopic display for detection of transient rhythm disturbances such as premature ventricular contractions (PVCs). It is not surprising that such events are often missed. We have found that transient events are regularly identified only when they occur with a frequency exceeding one per minute. Rhythm disturbances such as coupled PVCs or PVCs in which R waves interrupt the preceding T wave ("R on T"), which constitute indications for antiarrhythmic therapy, may go undetected if they occur less frequently than this.
The Epidemiologic Necropsy for Abdominal Aortic Aneurysm
Authors: Michael J. McFarlane
Journal: JAMA (1991)

<h3>To the Editor.</h3> —Dr McFarlane<sup>1</sup>examined the autopsy records from the University of Kansas Medical Center (KUMC) to find unexpected abdominal aortic aneurysms (AAA). From these data, he suggests that this technique may be used to estimate the incidence of AAA in the general population. On face value, this seems somewhat preposterous considering the multitude of factors that would skew the results, not the least being the decline in the autopsy rate over the study period of 1950 to 1984 and the relatively small population of only 7485 autopsies from KUMC. I have applied his technique to a very different population. I used the autopsy population of the Medical Examiner's Office of Broward County, Florida, from 1982 to 1990. In this group there were 13 525 autopsies and 202 ruptured AAAs. One hundred twenty-four of the 202 never were hospitalized, and 78 were diagnosed in the emergency department without
SUCCESSFUL AMPUTATION OF THE LEG AT 94 YEARS, WITH AN ACCOUNT OF A NEW OPERATION
Authors: C. W. Branch
Journal: BMJ (1906)

ME.\IORANDA.~~~~~~~~~~~~~~~~~~~MLYDIO" Jovv 133 patients were under 10 years of acre, and were playmates, their playground being the lobbies and stairs.The view that the waterelosets may have served as a source of in- fection is negatived by the fact that none of the adults (twenty-eight ini number) resident in those three flats were attacked, and it is not thought that the situation of the houses in respect of their water supply, some being placed on different sides of the stair, was a factor in the causation.Tthe evidence points strongly to personal in- fection during play, and, this method of spread of enteric fever being comparatively rare, it was deemed worthy to place these cases on record.