tbuckley/cabot-search huggingface dataset:
12 HIGH SVR12 WITH 16 WEEKS OF TEGOBUVIR AND GS-9256 WITH PEGINTERFERON-ALFA 2A AND RIBAVIRIN IN TREATMENT-NAIVE GENOTYPE 1 HCV PATIENTS
Authors: D.R. Nelson, E. Lawitz, V. Bain, N. Gitlin, T. Hawkins, P. Marotta, K. Workowski, S. Flamm, P.S. Pang, J.G. McHutchison, J. McNally, P. Urbanek, E.M. Yoshida
Journal: Journal of Hepatology (2012)
Humoral hypercalcemia of malignancy. Release of a prostaglandin-stimulating bone-resorbing factor in vitro by human transitional-cell carcinoma cells.
Authors: F R Bringhurst, B E Bierer, F Godeau, N Neyhard, V Varner, G V Segre
Journal: Journal of Clinical Investigation (1986)

Secretion by tumor cells of circulating bone-resorbing factors may frequently underlie the hypercalcemia that occurs in patients with malignancy. Efforts to identify the responsible mediators have been hampered by a lack of available human tumor cell systems suitable for study of the pathogenesis of the humoral hypercalcemia syndrome. We have established a transitional-cell carcinoma (TCC) line in vitro from a patient with humoral hypercalcemia. These cells are tumorigenic and cause hypercalcemia in athymic nude mice. Culture medium conditioned by TCC cells contains potent bone-resorbing activity in vitro, the physical and biological properties of which are similar to those of bone-resorbing activity present in the original patient's urine. The bone-resorbing activity of the TCC factor is accompanied by increased prostaglandin release from bone and is blocked by indomethacin and calcitonin. The TCC-derived bone-resorbing activity coelutes with prostaglandin-stimulating activity during gel filtration with an approximate molecular weight of 15,000. This activity is nondialyzable, stable to concentrated urea and reducing agents, and destroyed by boiling. The TCC factor does not increase cyclic AMP production in bone or kidney bioassays and does not exhibit transforming growth factor activity. We conclude that a unique macromolecular factor released by TCC cells causes bone resorption by a mechanism dependent upon stimulation of bone cell cyclooxygenase, and that this factor is the probable cause of the hypercalcemia in vivo. The TCC cell line provides a new model for study of the human humoral hypercalcemia syndrome.
P1209 FACTORS INFLUENCING RENAL FUNCTION IN PATIENTS RECEIVING TELAPREVIR TWICE DAILY OR EVERY 8 HOURS: RESULTS FROM THE PHASE III OPTIMIZE STUDY
Authors: M. Buti, K. Agarwal, Y. Horsmans, W. Sievert, E. Janczewska, S. Zeuzem, L. Nyberg, R.S. Brown, C. Hezode, M. Rizzetto, R. Parana, S. De Meyer, R. Demasi, D. Luo, K. Bertelsen, J. Witek
Journal: Journal of Hepatology (2014)
NON-INVASIVE ASSESSMENT OF STENT FRACTURE WITH THE STENT BOOST TECHNIQUE
Authors: Maria Papathanasiou, Evaggelia Zacharioglou, Periklis Davlouros, Lampros Papakosmas, Anastasia Damelou, Konstantinos Theodoropoulos, Vasileios Karantalis, Gerasimos Dimitropoulos, Georgia Mitropoulou, Ioanna Xanthopoulou, Grigorios Tsigkas, Dimitrios Alexopoulos
Journal: Journal of the American College of Cardiology (2010)
Interstitial Pregnancy Following Unilateral Salpingectomy
Authors: Rudolf Kirschner
Journal: JAMA (1961)

THE INFREQUENCY of interstitial pregnancy has been the subject of much discussion, but when it occurs following an ectopic pregnancy it becomes worthy of a report, because of its extreme rarity. Various figures have been reported with respect to the incidence of this abnormal condition. Crawford and Hutchinson<sup>1</sup>reviewed the literature for a period of one decade and reported that interstitial location was noted in from 0.07 per cent to 6.3 per cent of all pregnancies. In their own series of 300 cases these investigators found fewer than 1.0 per cent. Keenan,<sup>2</sup>as well as Leverton,<sup>3</sup>quotes more or less the same percentage of occurrence of interstitial pregnancies, namely, 1.0 to 2.0 per cent of all ectopic pregnancies. The occurrence of interstitial pregnancy following salpingectomy is, of course, rare and makes up a small percentage of all interstitial pregnancies. D'Errico<sup>4</sup>reviewed the literature extensively and
A direct comparison of two nonviral gene therapy vectors for somatic integration: in vivo evaluation of the bacteriophage integrase ϕC31 and the Sleeping Beauty transposase
Authors: Anja Ehrhardt, Hui Xu, Zan Huang, Jeffrey A. Engler, Mark A. Kay
Journal: Molecular Therapy (2005)

In this study we performed a head-to-head comparison of the integrase phiC31 derived from a Streptomyces phage and the Sleeping Beauty (SB) transposase, a member of the TC1/mariner superfamily of transposable elements. Mouse liver was cotransfused with a vector containing our most robust human coagulation factor IX expression cassette and the appropriate recombinase recognition site and either a phiC31- or a SB transposase-expressing vector. To analyze transgene persistence and to prove somatic integration in vivo we induced cell cycling of mouse hepatocytes and found that the transgene expression levels dropped by only 16 to 21% and 56 to 66% in mice that received phiC31 and SB, respectively. Notably, no difference in the toxicity profile was detected in mice treated with either recombinase. Moreover we observed that with the integrase-mediated gene transfer, transgene expression levels were dependent on the remaining noncoding vector sequences, which also integrate into the host genome. Further analyses of a hot spot of integration after phiC31-mediated integration revealed small chromosomal deletions at the target site and that the recombination process was not dependent on the orientation in which the phiC31 recognition site attached to the pseudo-recognition sites in the host genome. Coupled together with ongoing improvements in both systems this study suggests that both nonviral vector systems will have important roles in achieving stable gene transfer in vivo.
MUM1 expression in cutaneous CD30+ lymphoproliferative disorders: a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large-cell lymphoma
Authors: W. Kempf, H. Kutzner, A. Cozzio, C. A. Sander, M.C. Pfaltz, B. Müller, M. Pfaltz
Journal: British Journal of Dermatology (2008)

Background Primary cutaneous CD30+ lymphoproliferative disorders include lymphomatoid papulosis (LyP) and primary cutaneous CD30+ anaplastic large T‐cell lymphoma (ALCL). Because of overlapping histological features, it is impossible to distinguish ALCL from LyP on histological grounds. MUM1 (Multiple Myeloma oncogene 1) is expressed in systemic ALCL and classical Hodgkin lymphoma. MUM1 expression has not been studied in detail in CD30+ lymphoproliferative disorders. Objectives To examine the expression of MUM1 in CD30+ lymphoproliferative disorders and to assess its value as a diagnostic marker. Methods Thirty‐one formalin‐fixed paraffin‐embedded specimens of LyP (n =15), primary cutaneous ALCL (n =10), secondary cutaneous infiltrates of systemic ALCL (n =4) and secondary cutaneous Hodgkin lymphoma (n =2) were analysed by immunohistochemistry with a monoclonal antibody against MUM1. Results Positive staining for MUM1 was observed in 13 cases of LyP (87%), two cases of primary cutaneous ALCL (20%), four cases of secondary cutaneous ALCL (100%) and two cases of secondary cutaneous Hodgkin lymphoma (100%). In 11 of 13 LyP cases (85%), MUM1 was displayed by the majority, i.e. 50–90%, of the tumour cells. In contrast to LyP and secondary cutaneous ALCL, only two cases of primary cutaneous ALCL (20%) harboured MUM1‐positive tumour cells. There was a statistically significant difference in the expression of MUM1 between LyP and primary cutaneous ALCL (P =0·002) and between primary cutaneous ALCL and secondary cutaneous ALCL (P =0·015). Conclusions MUM1 expression is a valuable tool for the distinction of LyP and ALCL and thus represents a novel adjunctive diagnostic marker in CD30+ lymphoproliferative disorders.
Blood transfusion and renal allograft survival.
Authors: R W Blamey, M S Knapp, R P Burden, M Salisbury
Journal: BMJ (1978)

Thirty-two first renal transplantations with cadaveric allografts were reviewed to see how many of the recipients had received blood transfusions preoperatively. There was a significant difference in transplant survival between patients who had and patients who had not received blood transfusion before transplantation; this difference was entirely due to acute rejection within three months after transplantation in patients who had not received transfusion. Other factors studied had no effect on survival.
Carotid sinus baroreceptor activity in the nonhuman primate.
Authors: E Tomomatsu, L Huffman, J P Gilmore
Journal: Circulation Research (1983)

The carotid sinus of eight adult Macaca fascicularis monkeys was functionally isolated from the circulation and perfused with Krebs-Henseleit solution. The impulse activity in 65 carotid sinus baroreceptor fibers from the left carotid sinus nerve was studied during nonpulsatile perfusion and was compared with the impulse activity in 68 fibers from 10 adult mongrel dogs. Curves relating the discharge frequency to carotid sinus pressure were constructed. The baroreceptor fibers of the monkey had a significantly lower threshold, gain, pressure at the point of inflection, and plateau pressure than those of the dog. Hysteresis, as indicated by the separation of the stimulus-response curves obtained by increasing and then decreasing carotid sinus pressure, was observed. At any given pressure, the discharge frequency of baroreceptors was greater when carotid sinus pressure was increased than when it was decreased in both species. These results provide direct evidence that carotid sinus baroreceptors in the monkey are less sensitive to pressure changes than those in the dog.
Cigarette Smoking Is Associated With Low Glomerular Filtration Rate in Male Patients With Type 2 Diabetes
Authors: Salvatore De Cosmo, Olga Lamacchia, Anna Rauseo, Raffaella Viti, Loreto Gesualdo, Alessandra Pilotti, Vincenzo Trischitta, Mauro Cignarelli
Journal: Diabetes Care (2006)

The relationship between cigarette smoking and renal dysfunction in diabetes has predominantly been documented in patients with type 1 diabetes. The aim of the present study was to explore the relationship between cigarette smoking and glomerular filtration rate (GFR) in a large cross-sectional study carried out in male subjects with type 2 diabetes. The role of metabolic syndrome in modulating this relationship was also investigated.One hundred fifty-eight current smokers and 158 never smokers with type 2 diabetes were consecutively recruited. Low GFR was defined as GFR <60 ml/min per 1.73 m(2).The proportion of patients affected by low GFR was significantly higher in current smokers (20.9 vs. 12.0%, P = 0.03). The adjusted risk (odds ratio [OR]) of low GFR in current smokers was 2.20 (95% CI 1.14-4.26, P = 0.02) and markedly higher in patients from the first tertile of disease duration (4.27 [1.26-14.40], P = 0.02). When metabolic syndrome was added to the statistical model exploring the relationship between smoking and low GFR, the risk of low GFR showed a small change, although it did not become any more significant (1.84 [0.98-3.45], P = 0.06). Current smokers showed even higher free oxygen radical test unit values (560.0 +/- 91.5 vs. 442.7 +/- 87.2, P < 0.0001).In a large population of male patients with type 2 diabetes, the risk of low GFR is markedly enhanced by smoking and is at least partially mediated by metabolic syndrome.
THE INFLUENCE OF CLIMATE ON THE TREATMENT OF CHRONIC CATARRH OF THE MIDDLE EAR.
Authors: JOHN F. FULTON
Journal: JAMA (1884)

[Read in Section of Ophthalmology, Otology and Laryngology the American Medical Association, May 7, 1884] St. Paul, Minn. While I cannot, from the nature of the subject, give anything in this paper that is new to the experienced aurist, I hope to elicit a discussion and by so doing obtain the views held by American aurists upon a subject of immense importance. A little more than three years ago, in a private conversation with Dr. Francis Atwood, he made the remark that cases of chronic catarrh of the middle ear improved rapidly under the influence of the Minnesota climate. Dr. Atwood had a large practice and wide experience in treating this class of cases, extending over nine years of active work. He also had the opportunity to study the contrast in the results of treatment in a climate like that of Boston and that of Minnesota, and was deeply impressed
Demonstration of Schuffner's Dots in Benign Tertian Malaria
Authors: G. Discombe
Journal: BMJ (1945)

JOURNA1wxere quite healed.His pay-book showed that he had received two tetanus toxoid inoculations, one each on Oct. 18 and Dec. 18. 1941.COMMENT Clearly no massive amount of antitoxin was produced here, and the inference is that the immunity resulting from his pro- phylactic inoculations was slight or absent.Inoculations with tetanus toxoid cause antitoxin to appear in the circulation, but, more important, they also sensitize the reticulo-endothelial sys- tem, so that subsequent toxoid or toxin results in a rapid rise in circulating antitoxin.Data regarding the minimum protective level of antitoxln are based upon animal experiments, figures ranging from 0.001 to 0.1 i.u.'of antitoxin per c.cm. of serum being given.A primary two-dose inoculation of toxoid rarely produces more than 0.1 i.u. of antitoxin per c.cm., whereas a recall dose later on causes a marked rise (2-50 i.u.).This level falls steadily thereafter, but is readily raised again by further recall doses (Wolters and Dehmel, 1943).Hence it is unlikely that a high level of circulating anti- toxin was ever established in this case, and in the ensuing 26 months it must have fallen very low.There is therefore no need to postulate any original failure to form antitoxin, or any original absence or subsequent loss of reticulo-endothelial sensitivity, in order to explain the fatal, outcome.Although not proved bacteriologically, the clinical course suggests that the anal region was the source of the infection, and that the tetanus bacilli were introduced at the time of the operation.Such a hypothesis puts the incubation at seven days, which accords with his rapid death.Possibly it would have been better to delay operating; the current practice (Naunton Morgan.personal communication) is that with inflammation, thrombosis, or ulceration of internal haemorrhoids, operation is not undertaken for about six weeks.A recall dose of toxoid a week before operition might well have protected this patient, and it is suggested that this would be a reasonable precaution in such cases.My thanks are due to Brig.W. Foot, M.C..
Transfusion‐induced malaria in a splenectomized β‐thalassemia major patient and review of blood donor screening methods
Authors: Suresh K. Joishy, Cynthia G. Lopez
Journal: American Journal of Hematology (1980)

Abstract Transfusion‐induced malaria may be a serious threat to the life of a group of special patients: those who require many transfusions, those who have been treated with immunosuppressants, and those who have undergone splenectomy. We describe transfusion‐induced malaria in a β‐thalassemia major patient who had undergone splenectomy. Existing guidelines for screening and excluding donors who have or have had malaria are inadequate, and serologic screenings are too costly. We suggest some guidelines that may help prevent transfusion‐induced malaria and supply an index of suspect signs and symptoms as a key to diagnosis.
Susceptibility to hepatotoxicity in transgenic mice that express a dominant-negative human keratin 18 mutant.
Authors: N O Ku, S A Michie, R M Soetikno, E Z Resurreccion, R L Broome, R G Oshima, M B Omary
Journal: Journal of Clinical Investigation (1996)

Keratins 8 and 18 (K8/18) are intermediate filament phosphoglycoproteins that are expressed preferentially in simple-type epithelia. We recently described transgenic mice that express point-mutant human K18 (Ku, N.-O., S. Michie, R.G. Oshima, and M.B. Omary. 1995. J. Cell Biol. 131:1303-1314) and develop chronic hepatitis and hepatocyte fragility in association with hepatocyte keratin filament disruption. Here we show that mutant K18 expressing transgenic mice are highly susceptible to hepatotoxicity after acute administration of acetaminophen (400 mg/Kg) or chronic ingestion of griseofulvin (1.25% wt/wt of diet). The predisposition to hepatotoxicity results directly from the keratin mutation since nontransgenic or transgenic mice that express normal human K18 are more resistant. Hepatotoxicity was manifested by a significant difference in lethality, liver histopathology, and biochemical serum testing. Keratin glycosylation decreased in all griseofulvin-fed mice, whereas keratin phosphorylation increased dramatically preferentially in mice expressing normal K18. The phosphorylation increase in normal K18 after griseofulvin feeding appears to involve sites that are different to those that increase after partial hepatectomy. Our results indicate that hepatocyte intermediate filament disruption renders mice highly susceptible to hepatotoxicity, and raises the possibility that K18 mutations may predispose to drug hepatotoxicity. The dramatic phosphorylation increase in nonmutant keratins could provide survival advantage to hepatocytes.
Hospital admissions for anxiety peak in women over 60, UK study finds
Authors: N. Hawkes
Journal: BMJ (2014)

Hospital admissions for anxiety rise sharply in people aged over 60, especially women, new data from the Health and Social Care Information Centre have shown.1 Stress, on the other hand, peaks in girls aged 15-19 and in men in their 40s, and it declines significantly in both sexes in older age.

Stress and anxiety—terms that are often used interchangeably in everyday conversation—are in fact distinguishable. Stress is a normal response to an identifiable …
Epithelial Cell Proliferation Contributes to Airway Remodeling in Severe Asthma
Authors: Lance Cohen, Xueping E, Jaime Tarsi, Thiruvamoor Ramkumar, Todd K. Horiuchi, Rebecca Cochran, Steve DeMartino, Kenneth B. Schechtman, Iftikhar Hussain, Michael J. Holtzman, Mario Castro
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Despite long-term therapy with corticosteroids, patients with severe asthma develop irreversible airway obstruction.To evaluate if there are structural and functional differences in the airway epithelium in severe asthma associated with airway remodeling.In bronchial biopsies from 21 normal subjects, 11 subjects with chronic bronchitis, 9 subjects with mild asthma, and 31 subjects with severe asthma, we evaluated epithelial cell morphology: epithelial thickness, lamina reticularis (LR) thickness, and epithelial desquamation. Levels of retinoblastoma protein (Rb), Ki67, and Bcl-2 were measured, reflecting cellular proliferation and death. Terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL) was used to study cellular apoptosis.Airway epithelial and LR thickness was greater in subjects with severe asthma compared with those with mild asthma, normal subjects, and diseased control subjects (p=0.009 and 0.033, respectively). There was no significant difference in epithelial desquamation between groups. Active, hypophosphorylated Rb expression was decreased (p=0.002) and Ki67 was increased (p<0.01) in the epithelium of subjects with severe asthma as compared with normal subjects, indicating increased cellular proliferation. Bcl-2 expression was decreased (p<0.001), indicating decreased cell death suppression. There was a greater level of apoptotic activity in the airway biopsy in subjects with severe asthma as compared with the normal subjects using the TUNEL assay (p=0.002), suggesting increased cell death.In subjects with severe asthma, as compared with subjects with mild asthma, normal subjects, and diseased control subjects, we found novel evidence of increased cellular proliferation in the airway contributing to a thickened epithelium and LR. These changes may contribute to the progressive decline in lung function and airway remodeling in patients with severe asthma.
Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation
Authors: Karin Tarte, Julien Gaillard, Jean-Jacques Lataillade, Loic Fouillard, Martine Becker, Hossein Mossafa, Andrei Tchirkov, Hélène Rouard, Catherine Henry, Marie Splingard, Joelle Dulong, Delphine Monnier, Patrick Gourmelon, Norbert-Claude Gorin, Luc Sensebé
Journal: Blood (2009)
Prevention of rebleeding from oesophageal varices: two-year follow up of a prospective controlled trial of propranolol in addition to sclerotherapy
Authors: Christopher Vickers, Jonathan Rhodes, Ian Chesner, Peter Hillenbrand, John Dawson, Roy Cockel, Davis Adams, Humphrey O'Connor, Peter Dykes, Hugh Bradby, Roland Valori, Elwyn Elias
Journal: Journal of Hepatology (1994)
How Can Institutional Review Boards Best Interpret Preclinical Data?
Authors: James V. Lavery
Journal: PLoS Medicine (2011)

Among the many challenges facing institutional review boards (IRBs) is to predict whether the activities and interventions proposed in a clinical trial protocol are likely to yield net harm or net benefit for trial participants. IRBs take these questions very seriously, and never more so than in the review of first-in-human (FIH) trials, where interpreting findings about risks to humans from animal data requires a leap of faith, regardless of the quality of the available data.

In their paper published this week in PLoS Medicine [1], “Predicting harms and benefits in translational trials: Ethics, evidence, and uncertainty,” Jonathan Kimmelman and Alex London argue that decision-makers (which, from the context of their paper, I assume to mean IRB members) pay insufficient attention to threats to validity in preclinical studies and consult too narrow a set of evidence, thereby unnecessarily limiting predictions about risks and potential benefits for humans that they might otherwise be able to make. They advocate greater attention to the quality of preclinical evidence and to research on related agents. These strategies are meant to reduce what they call the “misestimation” of risks or anticipated benefits, which they argue “threatens the integrity of the scientific enterprise, because it frustrates prudent allocation of research resources”[1].

Kimmelman and London's proposal is likely to stimulate a great deal of constructive debate among clinical trialists, regulators, and other members of the research ethics community. In my brief comments here, I will attempt to open this debate by identifying a key aspect of their proposal that is likely to generate particular interest and perhaps even some controversy—that is, their framing of the problem in terms of how effectively decision-makers utilize evidence from preclinical or animal studies. Although IRB members often do not have deep grounding in the subtleties of research design and inferential statistics, it would be wrong to suggest that “misestimation” of risk and potential benefit arises solely from errors by IRB members (or other decision-makers).