tbuckley/cabot-search huggingface dataset:
Glutathione S-transferases in human liver cancer.
Authors: P C Hayes, L May, J D Hayes, D J Harrison
Journal: Gut (1991)

An immunohistochemical study of glutathione S-transferase (GST) expression in hepatocellular carcinoma and cholangiocarcinoma is described. Unlike most animal models of hepatic malignancy pi class GST was not consistently overexpressed in hepatocellular carcinoma. This tumour type either predominantly expressed alpha class GST or failed to express GST. By contrast, cholangiocarcinoma always expressed pi class GST, presumably reflecting the tissue of origin, since in human biliary epithelium pi class GST is the predominant GST. The variable expression of pi class GST which was observed in hepatocellular carcinoma may reflect transformation of hepatocytes damaged by toxins, since this GST can be induced after a chemical insult such as alcohol. As well as indicating the biochemical heterogeneity of hepatocellular carcinoma with respect to GST, this study indicates the need for further study of the nature of inherent drug resistance in these tumour types.
Toxic Effects of Iproniazid in a Patient with Angina
Authors: C. Papp, S. Benaim
Journal: BMJ (1958)

B: tory investigations showed an increase in gamma-globulin, a decreased pseudo-cholinesterase, and increased brom- sulphthalein retention in the absence of a rise in serum bilirubin.These findings were suggestive of hepatic dysfunction.
Debate on altruistic kidney donation was too simplistic
Authors: S. G. Potts
Journal: BMJ (2011)

The framing of the question for the debate on altruistic kidney donation allows only yes or no answers, thereby not recognising reality and artificially restricting the arguments on both sides.1 2

Encouragement ranges from the neutral presentation of relevant facts to already interested members of the general public on websites and the like to personally urging a previously uninterested patient in the course …
New Treatment Options for Tremors
Authors: Günther Deuschl
Journal: New England Journal of Medicine (2000)

The revival and refinement of stereotactic neurosurgery represent the most important therapeutic advance in the treatment of movement disorders in the past 30 years. The majority of patients who undergo surgery have Parkinson's disease, but this approach is also being used for patients with movement disorders such as dystonia and tremor, which is sometimes so severe that it cannot be adequately treated with medication. The study by Schuurman et al.1 in this issue of the Journal offers new information on neurosurgical treatment in such patients.Tremor is the most common movement disorder. The majority of affected patients have Parkinson's disease . . .
A Randomized, Double-Blind, Placebo-Controlled, Parallel Trial of Standardized Short Ragweed (RW) Sublingual Allergy Immunotherapy Liquid Extract (RW-SAIL) in Adult Subjects with Ragweed-Induced Allergic Rhinoconjunctivitis
Authors: Peter Creticos, Robert E. Esch, Peter Couroux, Deborah A. Gentile, Pina D'Angelo, Brad Whitlow, Michael Alexander, Terrance Coyne
Journal: Journal of Allergy and Clinical Immunology (2013)
Calcium Current Channels Induced by Catecholamines in Chick Embryonic Hearts Whose Fast Sodium Channels are Blocked by Tetrodotoxin or Elevated Potassium
Authors: KOKI SHIGENOBU, NICK SPERELAKIS
Journal: Circulation Research (1972)

In isolated ventricles of old (9-19 day) chick embryonic hearts made inexcitable by inactivating the fast sodium channels with either tetrodotoxin (TTX) or elevated external potassium, catecholamines induced slow electrical responses and concomitant contractions within 1-3 minutes. These slow responses had a higher threshold and propagated at a slower velocity than did the normal action potential. They were often graded and quite variable from one region of the heart to another. They were blocked by lanthanum or manganese (1 mM) and showed a dependence on the external calcium level. Strontium and barium could substitute for calcium. The slow channels were not completely inactivated when the external potassium concentration was raised until low membrane potentials of -10 to -25 mv were reached. The catecholamine-induced responses had a shape similar to that of the plateau component of the normal action potential, and cooling affected both in a similar manner. In some cases, slow responses persisted in TTX-blocked hearts even without the addition of exogenous catecholamines. Cyclic 3',5' AMP, dibutyryl cyclic AMP, theophylline, and caffeine partially mimicked the catecholamines, but usually the development of the response to these drugs was much slower. Prostaglandins, ryanodine, and acetylcholine had no effect. The order of effectiveness of the catecholamines was isoproterenol &gt; epinephrine ≥ norepinephrine &gt; dopamine ≥ dopa. Phenylalanine and tyrosine were ineffective. Isoproterenol produced a near-maximal effect at 5 x 10 -7 M. Propranolol blocked the catecholamine-induced effects. In young (2-5 day) hearts, there was no evidence that catecholamines produced a similar effect, and they did not have a positive inotropic action or an effect on the slow sodium channels. The results suggest that catecholamines quickly increase the density of divalent cation channels available in the sarcolemma of older chick hearts, thereby increasing the inward Ca 2- current and influencing contraction.
Abstract 2271: Effective therapy for advanced renal cell carcinoma using triptolide and TRAIL receptor agonists
Authors: Thomas S. Griffith, Erik L. Brincks, Tamara A. Kucaba, Britnie R. James, Veena Sangwan, Sulagna Banerjee, Ashok Saluja
Journal: Cancer Research (2014)

Abstract Metastatic renal cell carcinoma (RCC) is incurable. IFNα or IL-2 immunotherapy has been used for RCC for more than 20 years, but response rates remain low and these cytokines can generate toxic. More recently, administration of multikinase inhibitors or anti-VEGF receptor mAb has become popular, but these agents are largely palliative and tumor regression is common. The shortcomings in current therapeutic options for patients with metastatic RCC provide the rationale for the development of novel treatment protocols. Triptolide, a diterpene triepoxide from the medicinal herb Tripterygium wilfordii, can suppress cell growth and induce apoptosis in a range of human tumor cells. Further, triptolide also sensitizes tumor cells to TNF-related apoptosis-inducing ligand (TRAIL). The objective of this study was to determine the effectiveness of combining triptolide with TRAIL receptor agonists against RCC. In vitro, the combination of triptolide and recombinant human TRAIL protein decreased cell viability in the human RCC cell line ACHN cells compared with either treatment alone. This decrease in viability correlated with increased induction of apoptosis (positive Annexin V staining) and caspase activation. The triptolide-induced sensitization was accompanied by decreased HSP70, HSP27, and HSF1 expression, as well as increased surface expression of TRAIL-R2. Similar in vitro treatment of the mouse renal cell adenocarcinoma cell line, Renca, demonstrated that triptolide enhanced the killing of these cells by membrane-bound TRAIL or agonistic anti-DR5 mAb. In vivo treatment of mice bearing orthotopic and metastatic Renca tumors showed that combination therapy consisting of minnelide (a water soluble version of triptolide) and agonistic anti-DR5 mAb resulted in significantly decreased tumor burden and increased animal survival compared to either therapy alone. Collectively, our data suggest that triptolide sensitizes RCC cells to TRAIL-induced apoptosis, which is accompanied by decreased heat shock protein expression and altered TRAIL receptor expression. These data also suggest that the combination of TRAIL receptor agonists and triptolide may prove to be an effective treatment for metastatic RCC, especially at doses that show suboptimal tumoricidal activity when used individually. Citation Format: Thomas S. Griffith, Erik L. Brincks, Tamara A. Kucaba, Britnie R. James, Veena Sangwan, Sulagna Banerjee, Ashok Saluja. Effective therapy for advanced renal cell carcinoma using triptolide and TRAIL receptor agonists. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2271. doi:10.1158/1538-7445.AM2014-2271
London School of Tropical Medicine
Authors: C. Bruce
Journal: BMJ (1904)

most of what I had intended to say has been put before you much better than I could have done it.If I may be allowed to do so, I would ask you to consider Dr. West's remarks as embodying my views.I have not the ability or the very large experience of pneumothorax and pleural effusion which Dr. West possesses, but my own smaller experience-not alto- gether inconsiderable-leads me to endorse almost all that D.r.West has said.One slight point on which I would make some modifieation: I have had a fair number of cases of tuberculous pneumothorax, and in the great majority of these there was no need to aspirate.The urgent symptoms which always follow immediately after the per- foration have in my experience comparatively rarely been so,urgent as to need operative relief.My experience leads me to agree with Dr. Raw that many cases are best left alone.I am not altogether disposed to agree with Dr. Acland that purulent tuberculous effusions in the pleural sac should not be evacuated.Just as I advise the removal of local collections of pus in other parts, such as the limbs, in eases of pulmonary tuberculosis, so I should and do recom- mend the removal of pus from the pleural sac in these cases.I should like to endorse what Dr. Philip said as to the importance of keeping patients under observation for some time after the pleurisy is cured.It is just at this time that advance of the tubereulr us process in the lung may go on without recognition, if tl.e patient is not kept under observa- tion.Hygienic conditions of life, including a plentiful supply of fresh air, are important aids to the successful treatment of tuberculous and other pleural effusions.
Prostate Cancer Stem Cells: A New Target for Therapy
Authors: Norman J. Maitland, Anne T. Collins
Journal: Journal of Clinical Oncology (2008)

The existence of prostate cancer stem cells offers a theoretical explanation for many of the enduring uncertainties surrounding the etiology and treatment of the most commonly diagnosed tumor in US males. The study of cancer stem cells in prostate, as in other complex tissues, is critically dependent on the availability of pure cell populations, a situation complicated by the heterogeneity of prostate tumors. However, selection of cells with a CD133(+)/alpha 2 beta 1 integrin/ CD44(+) phenotype enriches for a tumor-initiating population from human prostate cancers. Among the most pressing needs is for enduring therapy in patients who have experienced failure of hormonal treatments. Because the putative cancer stem cell does not express androgen receptor, it is likely to be immune from most androgen-based therapies, and an inherent genetic instability would enable the tumor to develop the new variants present in hormone-refractory disease. Prostate cancer stem cells have a unique gene expression signature that can also be related to Gleason grade and patient outcome. The scarcity of cancer stem cells in a prostate tumor will probably limit their usefulness in cancer diagnosis and prognosis. However, the emergence of new stem-cell therapeutic targets not only will require new assays for efficacy (because of their relatively quiescent nature), but also holds real promise of more lasting treatments to augment those currently directed against the remaining tumor cells, which comprise 99.9% of tumor mass, but paradoxically have a poor tumor-initiating capacity.
President's Report to the House of Delegates
Authors: Gerald D. Dorman
Journal: JAMA (1970)

In the past two years, as President and President-elect of the American Medical Association, I have visited some 40 states and territories. I have been with many of you in your homes and have accumulated a rich storehouse of facts, knowledge, and understanding. What stands out preeminently in my experiences are the men and the women who are moving our profession to do an ever better job of giving the best possible care to all our people. Where health projects are prospering, there are dynamic personalities who enlist the dedication of the people around them and develop an esprit de corps and an élan which gets the job done. Where projects fail, it is due to the lack of ability to lead and to involve people in the cause. Experience is what the older man can contribute; youth brings imagination, energy, and optimism to the tasks before us. When an
Respiratory critical care HERMES syllabus: defining competencies for respiratory doctors
Authors: Antonio Artigas, Paolo Pelosi, Dominic Dellweg, Laurent Brochard, Miguel Ferrer, Jens Geiseler, Anders Larsson, Stefano Nava, Paolo Navalesi, Julie-Lyn Noël, Stylianos Orfanos, Paolo Palange, Bernd Schoenhofer, Theodoros Vassilakopoulos, Anita Simonds
Journal: European Respiratory Journal (2012)

“Coming together is a beginning, staying together is progress and working together is success.” Henry Ford (1863–1947).

From a medical perspective, European countries are growing closer together. An increasing number of physicians are crossing borders and swapping workplaces. In order to facilitate this development, the European Union (EU) adopted a directive dictating the equality of diplomas and medical board certificates within the EU [1]. Despite a number of initiatives, such as the “Lifelong Learning Programme: education and training opportunities”, for which the ERASMUS (European Region Action Scheme for the Mobility of University Students) is a sub-programme aimed at harmonising medical education during the early phases of medical training [2], there is a need to standardise knowledge and skills at later career stages in order to guarantee and harmonise the quality of patient care in Europe.

To address this, the HERMES project (Harmonised Education in Respiratory Medicine for European Specialists) was launched by the European Respiratory Society (ERS) in 2005 in order to harmonise education and training in respiratory medicine. With the success of this project, the ERS extended its scope to include a Paediatric Respiratory Medicine HERMES and subspecialty-focused HERMES projects. Thus, the Respiratory Critical Care HERMES project was launched in 2009. The project aims to provide educational standards and a training framework for respiratory critical care medicine using standardised modified Delphi surveys, facilitated group discussions and plenary sessions.

This is consistent with the ERS mission and has the ultimate goal of providing better patient care.

Similar projects in critical care have been launched in the past, such as the multi-society task force on competencies in pulmonary and critical care medicine reported by Buckley et al. [3] in 2009 and the development of core competencies for an international training programme in intensive care …
Assessment of the role of calcium ion in halocarbon hepatotoxicity.
Authors: W J Brattin, S D Pencil, R L Waller, E A Glende, R O Recknagel
Journal: Environmental Health Perspectives (1984)

Halogenated hydrocarbons (CCl4, BrCCl3, 1,1-dichloroethylene, bromobenzene) cause a wide spectrum of dysfunction and injury in liver cells. An early effect of CCl4, BrCCl3, and 1,1-dichloroethylene is destruction of the Ca2+-sequestering ability of the endoplasmic reticulum, and it has been suggested that this lesion leads to subsequent disruption of other cell functions. Work to test this hypothesis has begun in this and other laboratories. While it appears that redistribution of intracellular Ca2+ does occur following these agents, the importance of this in cell injury is not fully resolved. Current results suggest Ca2+ redistribution may be involved in some cases (e.g., surface blebbing caused by bromobenzene), but not in others (e.g., inhibition of lipid secretion by CCl4).
Optimization of solid supports for combinatorial chemical synthesis
Authors: Aubrey J. Mendonca, Xiao-Yi Xiao
Journal: Medicinal Research Reviews (1999)

Until recently, resins were used primarily for peptide and oligonucleotide synthesis. Recent advances in combinatorial chemistry have fostered increased acceptance of resins as supports for the synthesis of small molecule libraries. The methodology for selecting a resin bead that is ideal for the solid phase synthesis of small molecules is described in this review. The process of manufacturing a typical resin, the UniSphere®-200, is also explained. Furthermore, a new approach is proposed for the solid phase synthesis of analogs which are traditionally done in solution phase. This new procedure involves the use of building blocks attached to an activated resin. These building blocks are displaced by a functional group on the scaffold around which the analogs are built. Use of an excess of resin-linked building blocks drives the reaction to completion. Additionally, a newly developed, grafted surface solid support, is described. This support, the MicroTube,® can be used for the synthesis of large numbers of discrete molecules by a patented directed sorting method. © John Wiley & Sons, Inc. Med Res Rev, 19, No. 5, 451–462, 1999.
Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1.
Authors: G Ramadori, J D Sipe, C A Dinarello, S B Mizel, H R Colten
Journal: The Journal of Experimental Medicine (1985)

During the acute phase response to tissue injury or inflammation, the concentration of several plasma proteins change. Previous work (29-34) suggested a role for interleukin 1 (IL-1) in the acute phase response. The availability of recombinant-generated mouse IL-1 prompted a study designed to directly test the function of IL-1 and its mechanism of action on hepatic synthesis of two positive acute phase proteins (serum amyloid A [SAA] and complement factor B), and a negative acute phase reactant (albumin). Intravenous injection of purified recombinant-generated murine-IL-1 into C3H/HeJ endotoxin-resistant mice induced a dose-dependent increase in SAA-specific hepatic messenger RNA (mRNA), and an increase in SAA plasma protein concentration. In primary murine hepatocyte cultures, both the recombinant IL-1 and highly purified human IL-1 induced a dose- and time-dependent, reversible increase in expression of the SAA and factor B genes, and a decrease in albumin gene expression. This regulation is pretranslational, since the kinetics and direction of change in specific mRNA for SAA, factor B, and albumin correspond to the changes in synthesis of the respective proteins. Moreover, the effect of IL-1 was specific, since actin gene expression was unaffected, and the IL-1 response was inhibited by antibody specific for IL-1. These data provide direct evidence that a single mediator, IL-1, can effect the positive and negative changes in specific hepatic gene expression characteristic of the acute phase response.
Acute poisoning with Distalgesic.
Authors: I R Starkey, A A Lawson
Journal: BMJ (1978)

abnormality.The table shows that all subjects had raised serum TSH and low T4 concentrations.Cases 1-5 had immeasurable or low serum Tg values compatible with depressed or absent thyroid function.Cases 6-10 had normal or high Tg values, but in each case serum T3 concentration was normal (in one case, high).This implies the presence of functioning thyroid tissue and raises a query about the nature and degree of their hypothyroidism.Results in children with suspected hypothyroidism Case Serum T4 Serum T3 TSH Tg No
Long-term degenerative changes in aortic segment homografts, with particular reference to calcification
Authors: None Brock
Journal: Thorax (1968)

The object of this article is to present observations derived from a long-term follow-up (over a period of 8-17 years) of a personal series of aortic segment homografts from which certain important information arises. It will be shown that in those grafts prepared and preserved in a `fresh9 state, calcification has not occurred or has been trivial, whereas in 20 cases in which the graft has been prepared by freeze-drying, calcification is absent in only four, <i>i.e.</i>, 21%. Nineteen of these 20 have been traced up to date; only one is so far missing. In spite of calcification the functional result has remained excellent; in all, the graft was used to replace a segment of aorta resected for aneurysm or for coarctation. The high incidence of aortic wall calcification must assume clinical significance in relation to aortic valve homografting. This procedure is now well established and it is important to consider the future of the valve homograft, especially as most grafts are being prepared by freeze-drying. By analogy from observations on the rate of homografting of aortic segments, calcification is likely to occur at least in that portion of the aortic wall which carries the valve cusps. Impairment of function of the cusps or their involvement in the calcific process seems likely.
Doctor-patient communication. Clinical implications of social scientific research
Authors: H. Waitzkin
Journal: JAMA (1984)

Research in the social sciences has clarified the nature and problems of doctor-patient communication. The development of adequate communication skills is now a goal of training programs in the primary-care specialties. Social structural barriers impede effective communication, however, and information giving remains problematic. Doctors tend to underestimate patients' desire for information and to misperceive the process of information giving. The transmission of information is related to characteristics of patients (sex, education, social class, and prognosis), doctors (social-class background, income, and perception of patients' desire for information), and the clinical situation (number of patients seen). Doctors' nonverbal communication abilities are associated with outcomes of medical care such as satisfaction and compliance. Regarding the sociolinguistic structure of communication, doctors often maintain a style of high control, which involves many doctor-initiated questions, interruptions, and neglect of patients' "life world." Training programs and standards of clinical practice should emphasize that improved doctor-patient communication is both desirable and possible.A review is provided of the social science literature on doctor-patient communication, with emphasis on its implications for medical education and clinical practice. The transmission of information is related to characterisitics of patients (sex, education, social class, and prognosis), doctors (social class background, income, and perceptions of patients' desire for information), and the clinical situation (number of patients seen in a day). The role of doctors' nonverbal communication in affecting outcomes of care and the sociolinguistic structure of medical communication are also discussed.
Pleuropulmonary Reaction to Nitrofurantoin
Authors: Benjamin R. Robinson
Journal: JAMA (1964)

NITROFURANTOIN is frequently used for short and long term treatment of urinary tract infections. As with many drugs, various types of allergic or toxic reactions have occurred, the most serious of which is anaphylactic shock.<sup>1</sup> An unusual reaction to nitrofurantoin consisting of pulmonary infiltration and pleural effusion was reported by Israel and Diamond in May, 1962.<sup>2</sup>Three other reports have appeared in the foreign literature.<sup>3-5</sup> Because of its rarity of occurrence, but alarming picture that it may present, this case is presented. <h3>Report of a Case</h3> A 31-year-old white female was referred to the Woodland Memorial Hospital on April 23, 1963, complaining of chills, fever, and dyspnea. About three weeks before admission, she developed symptoms of a urinary tract infection and her physician started treatment with sulfisoxazole on April 9, 1963. This was changed to nitrofurantoin, 100 mg four times daily, on April 17, because of persisting