tbuckley/cabot-search huggingface dataset:
Phase I/II Study of 19-<i>nor</i>-1α-25-Dihydroxyvitamin D2 (Paricalcitol) in Advanced, Androgen-Insensitive Prostate Cancer
Authors: Gary G. Schwartz, M. Craig Hall, Diana Stindt, Suzanne Patton, James Lovato, Frank M. Torti
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We assessed the safety and efficacy of the vitamin D analogue, 19-nor-1α-25-dihydroxyvitamin D2 (paricalcitol), in patients with androgen-independent prostate cancer. Experimental Design: Patients received paricalcitol i.v. three times per week on an escalating dose of 5 to 25 μg (3-15 μg/m2). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were characterization of toxicity in this population, changes in serum parathyroid hormone (PTH), and survival. Results: A total of 18 patients were enrolled. No patient showed a sustained 50% drop in serum PSA, despite several large declines in PSA (e.g., 1,300 ng/mL). Paricalcitol was well tolerated. One instance of significant hypercalcemia, a serum calcium of 14.3 mg/dL, was observed at the highest dose (25 μg). At entry into the study, seven (41%) of the patients had elevated serum levels of PTH, which were significantly reduced by paricalcitol. Higher levels of serum PTH at study entry were significantly and negatively associated with survival (P &amp;lt; 0.01). Conclusion: No objective responses were seen in the primary end point. However, elevated serum levels of PTH, a common feature of advanced prostate cancer, were reduced by paricalcitol. Because elevated PTH is associated with increased cardiovascular and skeletal morbidity, including an increased risk for pathologic fracture, further evaluation of paricalcitol in the reduction of skeletal morbidity in advanced prostate cancer is warranted.
Statistics and death from meningococcal disease in children
Authors: Rafael Perera
Journal: BMJ (2006)

was not increased in children who did not receive penicillin in periods up to three hours taken to reach hospital.This suggests that a short delay without penicillin is not deleterious.Why did the original paper by Cartwright et al 1 (and a contemporaneous paper by Strang and Pugh 10 ) suggest a positive benefit from penicillin when we and our Danish colleagues show such a clear association with poor outcomes?One contributory explanation for the difference lies in the inclusion or exclusion of children in whom the general practitioner did not make the diagnosis of meningococcal disease and who were therefore unlikely to receive penicillin before admission.If we had included the 166 children who were seen but not diagnosed by general practitioners and who reached hospital at a median of 12 hours later without having parenteral penicillin before admission, the estimated crude odds of death after penicillin would be reduced from 5.96 to 1.45, at the upper limit of the 95% confidence interval of the estimate by Cartwright et al. 1 The current discrepancies can be answered only by a randomised controlled trial.Robert Booy contributed substantially to the design of the original study.Clare Phillips assisted with the data collection.
Pulmonary Arteriosclerosis and Cor Pulmonale Due to Recurrent Thromboembolism
Authors: P. J. BARNARD
Journal: Circulation (1954)

A long-term experiment will be described which has shown that repeated injections of minute autogenous blood clots in rabbits caused pulmonary arteriosclerosis and cor pulmonale. Pulmonary arterial lesions were of two main kinds with respect to circumference of the intimal coat: eccentric, ascribable to intimal incorporation of clot, and circumferential, probably ascribable to hypertension and vasospasm. A counterpart to this animal experiment is probably to be found in human pathology, as suggested by certain case reports, by the pathology of lymphangitis carcinomatosa and by evidence that circulating blood is not clot free.
Alterations in Metabolism Mediated by Environmental Change and Disease
Authors: I. A. Bernstein
Journal: JAMA (1964)

THE CELL can make many of the vast number of chemical substances it requires from a relatively small number of compounds available to it. It depends on an extensive, well modulated, complex of reactions to carry on necessary chemical activities for its health. Some clinical entities are known to be associated with specific abnormalities in the cell's chemical functions; it is reasonable to expect that future studies will indicate metabolic etiologies for other diseases. The radioactive isotope as a tracer provides a means of studying various segments of a chemical reaction system, in situ. By determining distribution of a radioactive isotope of carbon (C<sup>14</sup>) in certain compounds of the cell after administration of compounds specifically labeled with this isotope, one can study (a) biosynthetic pathways utilized, (b) concentrations of intermediates (ie, pool sizes) involved, (c) equilibria of various reactions on pathways as well as those side reactions related to the pathways, and (d) rates
Renal Injury Following Exposure to Carbon Tetrachloride
Authors: Marshall Clinton
Journal: New England Journal of Medicine (1947)

MOST physicians associate carbon tetrachloride poisoning with serious liver damage and jaundice. This is not surprising, since knowledge of this substance stems from medical-school teaching, in which carbon tetrachloride was cited as an etiologic agent in toxic cirrhosis or acute atrophy of the liver and emphasis was placed on the risk of liver damage following the improper use of carbon tetrachloride as a vermifuge. The association of carbon tetrachloride with liver injury is also due in part to familiarity with its use as a hepatotoxic agent in animal experiments.1 2 3 It is not generally recognized, however, that the inhalation of carbon . . .
"SUGGESTION" IN THE TREATMENT OF DISEASE
Authors: H. Morris
Journal: BMJ (1910)

~~~~~~~~~~~~~~~~~~~~~~ILEICAL JOUBNAZ 1457 attain to it.The physician knows there is no more arrant delusion than to suppose sickness to be a convenient season for inspiration; it is rather a season of apathy, or of despondency-Domine quid multiplicasti !At best the mystic quietism of the bedridden is not a virile enthusiasm; it is pallid and tenuous in fibre.Still it is true no doubt that the solitary and disconsolate heart,
Coagulase-Negative Staphylococcus within Neutrophils in Acute Leukemia
Authors: Francisco J Ortuño, Inmaculada Heras
Journal: New England Journal of Medicine (2005)

In this 43-year-old man with a relapse of acute myelomonocytic leukemia, fever developed during salvage chemotherapy. There was no growth in 19 blood cultures. On day 35, 1-μm inclusions were observed within peripheral-blood neutrophils.
Different patterns of intestinal transit time and anorectal motility in painful and painless chronic constipation.
Authors: G A Lanfranchi, G Bazzocchi, C Brignola, M Campieri, G Labo
Journal: Gut (1984)

Anorectal motility and gastrointestinal transit time were studied in 25 patients complaining of non-organic constipation. Colonic pain was reported by 14 patients, it was absent in the remaining 11. The group with painful constipation was composed of four men and 10 women and age onset of the symptom was 22.1 +/- 5.1 years. The other group was composed only of women and painless constipation was reported to have begun at 7.9 +/- 2.2 years previously. In the group presenting painful constipation higher values of the anal maximum resting pressure, of the amplitude of the rectoanal inhibitory reflex, lower values of sensation threshold, need to evacuate, maximum tolerable volume were recorded, in comparison with those registered in the painless constipation group. All these differences were significant. In the latter group the total transit time was always very slow (186.0 +/- 4.7 h), while it was quite variable in the other group, so that the mean was in the normal range (79.0 +/- 10.0 h). The data show that two different patterns of motor abnormalities can be recognised in constipated patients. The presence of colonic pain can suggest the characteristics of the underlying motor abnormality.
Evidence for cell-mediated immune mechanisms in the pathology of pemphigus
Authors: D. ZILLIKENS, A. AMBACH, A. ZENTNER, R. DUMMER, M. SCHUSSLER, G. BURG, E.B. BROCKER
Journal: British Journal of Dermatology (1993)

Pemphigus is an autoimmune blistering disease in which autoantibodies have clearly been shown to be pathogenic. Because autoantibodies are also found in uninvolved skin, further mechanisms may be important in the development of pemphigus lesions. In addition to granulocytes, mononuclear cells are commonly found in pemphigus lesions. To elucidate the role of mononuclear cells in the pathology of this disease, we determined the levels of soluble interleukin-2 receptor in blister fluid and serum samples from pemphigus patients prior to treatment. The interleukin-2 receptor (IL-2R) is expressed on activated mononuclear cells. Depending on its rate of synthesis, a portion is released from the cell surface in a soluble form (sIL-2R). In blister fluid, sIL-2R levels were 2186 +/- 288 U/ml (+/- SD), which was significantly higher than levels in concurrently obtained serum samples (1299 +/- 165 U/ml; P < 0.001). In suction blisters in volunteers, and in patients with second-degree burns or friction-induced bullae, sIL-2R levels were normal in both blister fluid and serum. In pemphigus patients, sIL-2R serum levels continuously declined during systemic therapy, correlating with disease activity. Immunohistological studies demonstrated a marked increase in IL-2R+ cells in both the epidermis and dermis of lesional skin compared with perilesional skin. In the dermis, CD3+ T cells predominated, whereas monocytes/macrophages were most frequent in the epidermis. In pemphigus vulgaris, monocytes/macrophages were restricted to the basal keratinocytes, whereas in pemphigus foliaceus, they were found throughout the lesional epidermis. Our data indicate that activated mononuclear cells are present in lesional skin of pemphigus patients, and may contribute to the pathology of this disease.
Rubella
Authors: Saul Krugman, Robert Ward
Journal: New England Journal of Medicine (1958)

THE association of rubella in pregnancy with congenital malformations, stillbirths and abortions is now common knowledge. Maternal rubella infection may be followed by congenital cataracts, deafness, microcephaly, mental retardation and congenital heart disease. These malformations may occur singly or in combination. The original observation of this hazard of rubella in pregnancy was reported by Gregg,1 of Australia, in 1941. Since that time it has been amply confirmed by others from all parts of the world.2 3 4 It has been postulated that rubella virus damages the fetal tissues that are multiplying most rapidly at the time of infection. Thus, rubella may be . . .
Acute gastric ulcer associated with gamma knife treatment (conformal stereotactic radiotherapy) of recurrent hepatocellular carcinoma
Authors: C. Chang, C. Tu, T. Chiang, H. Wang
Journal: Endoscopy (2007)

Figure 1 A 73-year-old man received one course of gamma knife radiotherapy (conformal stereotactic radiotherapy) for recurrent hepatocellular carcinoma, with a total dose of 45 Gy given within 1 month. Three days after finishing radiotherapy, he developed tarry stools. At esophagogastroduodenoscopy, he was found to have a large gastric ulcer on the lesser curvature and the anterior wall of the antrum, which had an irregular shape and margins (a) and several exposed vessels (b).
Data mining can support quality assurance
Authors: Arthur R Jones
Journal: Journal of the Royal Society of Medicine (2009)

Doctors Hockey and Marshall’s essay on the need to train doctors in quality improvement, citing its successful use by manufacturers and US doctors1 is timely as it is now nearly a century since the first suggestions that hospitals might use industrial methods of management and surgeons provide formal quality assurance. In the meantime manufacturers have evolved into world-class companies, able to meet global demand, by paring processes down to provide goods of a narrow albeit protean quality, ones which satisfy customer requirements at an acceptable price. Their lean processes are rigidly defined and incorporated into comprehensive systems of Total Quality Management (TQM) so no activity, be it lean manufacturing or continuous improvement, functions in isolation. But despite the opinion that TQM concepts apply equally to manufacturing and service industries no company providing personal healthcare has succeeded in joining the world-class paragons and there is a corresponding absence of TQM at unit level in healthcare. In the case of surgery, a service in some respects close to the ethos of the craft workshops which developed into factories, there are fewer than a dozen reports containing the terms ‘surgery’ with ‘TQM’ in Pubmed. Of these only one used outcome of introducing TQM as its topic (it found little effect).2 This paucity is in contrast with an abundance of publications about clinically-driven surgical quality. The difference in activity in a lively discipline with an obvious commitment to quality is likely to reflect difficulty of extending a linear model into an environment which is complex and adaptive.3 As this healthcare environment is also knowledge-based and creates vast amounts of data doctors with an interest in quality assurance should familiarize themselves with data mining for patterns of care as an aid to discovering better processes4 and meeting inequalities in care.5
MDR1 expression predicts outcome of Ph+ chronic phase CML patients on second-line nilotinib therapy after imatinib failure
Authors: M Agrawal, B Hanfstein, P Erben, D Wolf, T Ernst, A Fabarius, S Saussele, D Purkayastha, R C Woodman, W-K Hofmann, R Hehlmann, A Hochhaus, M C Müller
Journal: Leukemia (2014)
Self-deceive to countermine detection
Authors: Hui Jing Lu, Lei Chang
Journal: Behavioral and Brain Sciences (2011)

Abstract Having evolved to escape detection of deception completely, self-deception must respond to social conditions registering different probabilities of detection. To be adaptive, it must have a mechanism to keep truthful information temporarily from the self during deception and retrieve it after deception. The memory system may serve this mechanism and provides a paradigm in which to conduct research on self-deception.
THE RÔLE OF TRANSILLUMINATION IN DISEASES OF THE NASAL ACCESSORY SINUSES
Authors: EDWARD L. PRATT
Journal: JAMA (1923)

The majority of textbooks dealing with diseases of the nasal accessory sinuses affirm or concede that transillumination is a more or less valuable diagnostic agent in conditions affecting the maxillary and frontal sinuses. In practice, however, one is surprised to find how infrequently it is used, and with what skepticism its value is appraised. As a result, the diagnosis of maxillary sinusitis, which should be the easiest to diagnose of all the sinuses, is missed in an astonishingly large percentage of cases. In a recent article, Billings<sup>1</sup>says: "Diagnosis is the most important factor in the practice of medicine. Until the diagnosis is made, treatment may be ineffectual and often is irrational." The importance—economic as well as physical—of making an early diagnosis in sinus disease is too obvious a fact to need embellishment. It is nevertheless true that an early diagnosis of sinus disease is seldom made by the
Variations in use of cardiology services in a health authority: comparison of coronary artery revascularisation rates with prevalence of angina and coronary mortality
Authors: N. Payne, C. Saul
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To explore the relation between rates of coronary artery revascularisation and prevalence of angina to assess whether use of health services reflects need. <b>Design:</b> Prevalence of angina symptoms determined by postal questionnaire on 16 750 subjects (18 to 94 years). Comparison of data on use of coronary artery revascularisation with prevalence of symptoms and mortality from coronary heart disease. <b>Setting:</b> Health authority with population of 530 000. <b>Subjects:</b> Patients admitted to hospital for coronary heart disease; patients who died; and patients undergoing angiography, angioplasty, or coronary artery bypass graft. Cohort of 491 people with symptoms from survey. <b>Main outcome measures:</b> Pearson9s product moment correlation coefficients for relation between variables. <b>Results:</b> Overall, 4.0% (95% confidence interval 3.7% to 4.4%) of subjects had symptoms. Prevalences varied widely between electoral wards and were positively associated with Townsend score (<i>r</i> =0.79; P&lt;0.001), as was mortality, but the correlation between admission rates and Townsend score was less clear (<i>r</i> =0.47; P&lt;0.01). Revascularisation rate and Townsend score were not associated. The ratio of revascularisation to number experiencing symptoms was inversely related to Townsend score (<i>r</i> =-0.67; P&lt;0.001). The most deprived wards had only about half the number of revascularisations per head of population with angina than did the more affluent wards. In affluent wards 11% (13/116) of those with symptoms had coronary angiograms compared with only 4% (9/216) in poorer wards (χ<sup>2</sup>=4.96; P=0.026). Townsend score also inversely correlated with revascularisations per premature death from coronary heart disease (<i>r</i> =-0.55; P&lt;0.01) and revascularisations per admission for myocardial infarction (<i>r</i> =-0.47; P&lt;0.01). <b>Conclusion:</b> The use of interventional cardiology services is not commensurate with need, thus exhibiting the inverse care law. <h3>Key messages</h3> There is a large local variation in mortality from coronary heart disease and in the prevalence of angina symptoms and both of these are strongly correlated with material deprivation Morbidity, as prevalence of angina symptoms, shows the same relation as mortality The use of coronary artery revascularisation services is not commensurate with need and exhibits the inverse care law even though the supply of care is the same Further work is required to ensure that the use of and access to facilities ensures that health care is targeted where it will have the greatest effect
TALEN-Mediated Somatic Mutagenesis in Murine Models of Cancer
Authors: Shuyuan Zhang, Lin Li, Sara L. Kendrick, Robert D. Gerard, Hao Zhu
Journal: Cancer Research (2014)

Cancer genome sequencing has identified numerous somatic mutations whose biologic relevance is uncertain. In this study, we used genome-editing tools to create and analyze targeted somatic mutations in murine models of liver cancer. Transcription activator-like effector nucleases (TALEN) were designed against β-catenin (Ctnnb1) and adenomatous polyposis coli (Apc), two commonly mutated genes in hepatocellular carcinoma (HCC), to generate isogenic HCC cell lines. Both mutant cell lines exhibited evidence of Wnt pathway dysregulation. We asked whether these TALENs could create targeted somatic mutations after hydrodynamic transfection into mouse liver. TALENs targeting β-catenin promoted endogenous HCC carrying the intended gain-of-function mutations. However, TALENs targeting Apc were not as efficient in inducing in vivo homozygous loss-of-function mutations. We hypothesized that hepatocyte polyploidy might be protective against TALEN-induced loss of heterozygosity, and indeed Apc gene editing was less efficient in tetraploid than in diploid hepatocytes. To increase efficiency, we administered adenoviral Apc TALENs and found that we could achieve a higher mutagenesis rate in vivo. Our results demonstrate that genome-editing tools can enable the in vivo study of cancer genes and faithfully recapitulate the mosaic nature of mutagenesis in mouse cancer models. Cancer Res; 74(18); 5311-21. ©2014 AACR.
Myeloid differentiation antigen defined by a monoclonal antibody IF10
Authors: K. Yamada, N. Okabe, H. Saito, R. Suzuki, K. Kumagai
Journal: American Journal of Hematology (1983)

Abstract A monoclonal antibody of IgM class that defines the antigen present on human peripheral blood granulocytes was produced and characterized. This monoclonal antibody (IF10) was made from a single fusion between P3‐X63‐Ag8‐U1 (P3U1) myeloma cells and splenoctyes from a BALB/c mouse immunized against human cultured monocytoid cell line THP‐1 cells. IF10‐defined antigen(s) was expressed on the cells of granulocyte lineage such as peripheral blood granulocytes and metamyelocytes, myelocytes, promyelocytes, and a part of myeloblasts in the normal bone marrow, whereas it was not detected on resting and activated T lymphocytes, B lymphocytes, adherent monocytes, and thymocytes. The IF10‐defined antigen was also expressed on cultured monocytoid cell lines as well as myeloid and myeloid/erythroid (K‐562) cell lines. T lymphoblastoid cell lines, particularly those representing the T cells at an early thymocyte level, and a part of null cell lines were also reactive to IF10. Therefore, IF10 may be a unique monoclonal antibody that defines an antigen(s) which is expressed on almost whole stages of granulocytes and early stages of macrophages and T‐cell lineages, and possibly during very early stages of erythroid lineage.
Acute rejection of murine bone marrow allografts by natural killer cells and T cells. Differences in kinetics and target antigens recognized.
Authors: W J Murphy, V Kumar, M Bennett
Journal: The Journal of Experimental Medicine (1987)

Lethally irradiated C.B-17 +/+, C.B-17 scid/scid (severe combined immunodeficiency, SCID), BALB/c-nu/nu (nude), and C57BL/6 (B6) mice were challenged with H-2-homozygous or H-2-heterozygous totally allogeneic bone marrow cell (BMC) grafts. Some of the irradiated mice were immunized simultaneously with large numbers of irradiated marrow and spleen cells syngeneic with the viable BMC transferred. Irradiated SCID and nude mice, devoid of T cells but with normal NK cell function, were able to reject H-2-homozygous BMC grafts within 4 d. However, they were unable to reject H-2-heterozygous BMC allografts by 7 d even if they were immunized. B6 and C.B-17 +/+ mice were able to reject H-2 heterozygous BMC allografts by 7-8 d, but not as early as 4 d, if they were immunized. The rejection of H-2-homozygous BMC on day 4 was inhibited by administration of anti-NK-1.1 antibodies, but not by anti-Lyt-2 antibodies. Conversely, the rejection of H-2-heterozygous allogeneic BMC on day 8 was prevented by anti-Lyt-2 but not by anti-NK-1.1 antibodies. The data indicate that both NK cells and Lyt-2+ T cells can mediate rejection of allogeneic BMC acutely, even after exposure of mice to lethal doses of ionizing irradiation. NK cells appear to recognize Hemopoietic histocompatibility (Hh) antigens on H-2 homozygous stem cells. The inability of SCID and nude mice to reject H-2 heterozygous totally allogeneic BMC indicate that NK cells do not survey donor marrow cells for self H-2 antigens and reject those cells that express nonself H-2 antigens. The T cells presumably recognize conventional H-2 antigens (probably class I) under these conditions.
TCT-200 Multi Center, Prospective, Randomized, Single Blind, Consecutive Enrollment Evaluation a Novolimus-Eluting Coronary Stent System with Bioabsorbable Polymer Compared to a Zotarolimus-Eluting Coronary Stent System: Long Term (24- Month) Clinical Follow Up from the EXCELLA BD Study
Authors: Stefan Verheye, Alexandre Abizaid, Roberto Botelho, Ricardo A. Costa, Luiz F. Tanajura, Katsuhisa Waseda, Manejeh Yaqub, Lynn Morrison, Sara Toyloy, Peter J. Fitzgerald, Joachim Schofer
Journal: Journal of the American College of Cardiology (2013)