tbuckley/cabot-search huggingface dataset:
Adherence to advance directives: Advance directive needs to include additional elements
Authors: G. W Knox
Journal: BMJ (2003)

Editor—Those of us who have made advance directives can only be dismayed and concerned by Thompson et al's assumption that there will always be ambiguity.1 Firstly, doctors can strangely assume that patients might aspire to spend their last days demented in a residential home. Secondly, this assumption is enough to justify giving an antibiotic to prolong everyone's agony, mainly that of the patient.

Prescribing an antibiotic is the easy option; many of us have done it. I will always remember the withering look coupled with the remark “Why did you do it?”of a most distinguished, very elderly lady to whom I administered a parenteral antibiotic when she was delirious with pneumonia. She recovered and eventually developed dementia. There was no alternative to the antibiotic: there was no advance directive. Higgs commented in the BMJ that pneumonia, the old person's friend, may be dismissed with a wave of the prescribing pen—but what if the old person wishes the friend to call?2

What can be done to counteract the ambiguity? The hypothetical advance directive, although apparently fully comprehensive and perhaps thought to be irrefutable, should additionally include:



A statement of general beliefs and aspects of life that the person values. My own statement is long and detailed and includes the hope that I will not end up a burden to my carers, and that I will not have inflicted on me a meaningless struggle against unacceptable mental or physical disability by my doctors


A statement naming a proxy who would help the doctors with interpreting the advance directive.






If my directive with these additions is still ignored I hope that my relatives would not hesitate to sue for assault or negligence.
Roles of ICAM-1 for Abnormal Leukocyte Recruitment in the Microcirculation of Bleomycin-induced Fibrotic Lung Injury
Authors: NAGATO SATO, YUKIO SUZUKI, KAZUMI NISHIO, KOICHI SUZUKI, KATSUHIKO NAOKI, KEI TAKESHITA, HIROYASU KUDO, NAOKI MIYAO, HARUKUNI TSUMURA, HIROSHI SERIZAWA, MAKOTO SUEMATSU, KAZUHIRO YAMAGUCHI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

To assess the importance of endothelial intercellular adhesion molecule-1 (ICAM-1) in microvascular leukocyte kinetics in diseased lungs, we investigated the transitional changes in ICAM-1 expression, vascular diameter, and leukocyte behavior in rat pulmonary microcirculation during the development of acute lung injury (ALI) and chronic fibrosis (FIB) evoked by bleomycin (BLM). Observations were made in the isolated perfused lung with a real-time confocal laser luminescence microscope. Microvascular cell kinetics were evaluated by measuring the behavior of fluorescence- labeled leukocytes and erythrocytes in the presence or absence of anti-ICAM-1 monoclonal antibody (1A29). Arteriolar ICAM-1 showed little change at any time after BLM treatment. Venular ICAM-1 was first enhanced at the initial phase of ALI followed by the second upregulation at the early phase of FIB. Capillary ICAM-1 showed a sustained increase at both ALI and FIB. Arteriolar and venular diameters were not altered but capillary diameter decreased during ALI and early FIB stages. Although firm adherence of leukocytes to arteriolar and venular walls was not observed, rolling leukocytes were increased in venules both at the initial phase of ALI and at the early phase of FIB. The leukocyte rolling in venules correlated well with transitional changes in ICAM-1 and was inhibited by 1A29. Sustained entrapment of leukocytes in capillaries was attributed to changes in vascular diameter as well as augmented ICAM-1. In conclusion, ICAM-1 plays an important role in microvascular leukocyte recruitment in both ALI and FIB in the BLM-injured lung.
Abstract 653: Stat3 as a molecular signature and therapeutic target for inflammatory breast cancer
Authors: Nanda K. Thudi, Pijus K. Mandal, John S. McMurray, Fredika M. Robertson
Journal: Cancer Research (2010)

Abstract Inflammatory breast cancer (IBC) is the most aggressive and lethal of all breast cancers. There is little known about the molecular signatures of IBC with the exception that these breast cancers commonly over-express E-cadherin and Rho C GTPase and exist as tumor emboli within dermal lymphatics. In addition, IBC tumor emboli exhibit characteristics of tumor initiating cells, i.e., cancer stem cells. Another interesting characteristic of IBC tumors is their ability to undergo vasculogenic mimicry, forming tube-like structures that abrogate the need of this very aggressive tumor type to induce the development of angiogenic endothelium. In vitro under low adherence culture conditions, IBC cells readily form tumor spheroids that contain ”label retaining” cells and exhibit self-renewal. In addition, when cultured as tumor spheroids in 3 dimensions, they express high levels of the phosphorylated form of the signal transducer and activator of transcription 3 (phospho-stat3), recently shown to regulate survival of embryonic stem cells. From a panel of newly developed novel stat3-targeted peptidomimetics, we found that the lead compound, designated as PM-73G, inhibited phospho-stat3, which was associated with blockade of the robust invasion, anchorage independent growth in soft agar and vasculogenic mimicry exhibited by IBC tumor cells without a significant anti-proliferative effect. Using array-based PCR and protein analysis, we found a specific pattern of inhibition of genes/proteins within the Jak/Stat pathway by PM-73G. Results of comparative studies using both PM-73G and stat3 shRNA demonstrate a role for stat3 in maintenance of the cancer stem cell phenotype exhibited by IBC tumor spheroids. Taken together, these studies suggest that stat3 may serve both as a molecular signature of IBC and as a target for development of effective therapeutics for this lethal form of breast cancer that contain tumor cells exhibiting a cancer stem cell phenotype. (Funded by The Susan G. Komen For The Cure Promise Grant KGO 81287 (FMR), The State of Texas Rare and Aggressive Breast Cancer Fund (FMR), NIH NCI CA096652 (JSM) and Center for Targeted Therapy at The University of Texas M.D. Anderson Cancer Center and the Texas Institute for Drug and Diagnostic Development at The University of Texas, Austin. (FMR &amp; JSM). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 653.
Disruption of gastric barrier function by luminal nitrosative stress: a potential chemical insult to the human gastro-oesophageal junction
Authors: N Ara, K Iijima, K Asanuma, J Yoshitake, S Ohara, T Shimosegawa, T Yoshimura
Journal: Gut (2007)

The human gastro-oesophageal junction is exposed to abundant amounts of luminal reactive nitrogen oxide species (RNOS) derived from the enterosalivary re-circulation of dietary nitrate. The aim of this study is to investigate the direct effects of luminal RNOS on the adjacent gastric barrier function using an ex vivo chamber model.A chamber model in which the rat gastric mucosal membrane was mounted between the two halves of a chamber was designed to simulate the microenvironment of the lumen and the adjacent mucosa of the gastro-oesophageal junction. On the mucosal side of the chamber, RNOS were generated by the acidification of physiological concentrations of sodium nitrite. The epithelial barrier function was evaluated by electrophysiological transmembrane resistance, and membrane permeability with [3H]mannitol flux. The expression of occludin was evaluated by immunohistochemistry and immunoblotting. Dinitrosyl dithiolato iron complex (DNIC) was also measured by means of electron paramagnetic resonance spectroscopy to confirm the diffusion of RNOS from the mucosal lumen into the mounted mucosa.The administration of acidified nitrite to the mucosal lumen caused both a decrease in transmembrane resistance and an increase in epithelial permeability, suggesting a disturbance of the gastric barrier function. These changes were accompanied by a derangement of the expression of occludin. The diffusion of luminal RNOS into the mounted membrane was confirmed by showing the generation of DNIC within the tissue.Simulating the microenvironment of the human gastro-oesophageal junction, this study demonstrated that RNOS generated luminally at the human gastro-oesophageal junction can derange the barrier function of the adjacent tissue by disrupting the tight junction.
Scientists warn that Paris summit is last chance to prevent fatal temperature rise
Authors: N. Hawkes
Journal: BMJ (2015)

The earth can be saved from catastrophic climate change but only if bold action leads to a global agreement at the climate summit in Paris in December, leading climate scientists have said.

In a statement issued for Earth Day, they said that the Paris meeting will be the last chance to prevent global temperatures rising by more than 2°C, which they see as the upper safety limit. Achieving this target would require carbon releases into the atmosphere to peak by 2020 and to decline to near zero by 2050.

This is possible, but only just, Johan Rockstrom of the Stockholm Resilience Centre told a briefing at the Science Media Centre in …
989. Toward Multivalent Adeno-Based Vaccine for Malaria: Effects of Promoter Strength on Immunogenicity and Vaccine Efficacy
Authors: Joseph T. Bruder, Maureen E. Stefaniak, Duncan McVey, Damodar Ettyreddy, Noelle B. Patterson, Fe Baraceros, Joseph J. Campo, C.R. King, Denise L. Doolan
Journal: Molecular Therapy (2005)

Malaria is the most devastating parasitic disease affecting humans. Each year 300-500 million people become infected with the parasite and more than 1.5 million people, primarily children, die of the disease. The feasibility of a malaria vaccine is supported by the demonstration of protective immunity following exposure to the intact Plasmodium parasite.
Comparative safety and efficacy of short ragweed extracts differing in potency and composition in the treatment of fall hay fever
Authors: P. C. Turkeltaub, G. Campbell, J. E. Mosimann
Journal: Allergy (1990)

One high potency (HP) and two low potency (LP) commercial whole short ragweed (WSR) extracts were assayed for relative potency (RP) by antigen E (AgE‐Amb a 1), RAST inhibition, and parallel line bioassay (PLBA). The RP of the HP extract (300 (μg AgE) was equal to the reference WSR, but the LP extracts were only ∼ 0.01 of the RP of the reference. Each extract was administered to fall hay fever patients with skin sensitivity to WSR (≤ 10 −3 μg/ml AgE for sum of erythema = 50 mm) to the maximum tolerated dose, or 0.5 cc of the concentrate, by either a 9‐ or 40‐dosc regimen. HP‐treated patients had significantly lower symptom scores than untreated controls. No significant difference was noted in the total symptom scores between HP and LP extract‐treated patients. Despite ∼ 100‐fold differences in the RP of HP versus LP extracts, both produced similar frequencies of severe systemic and severe late phase local reactions. Furthermore, when RP of HP and LP extracts were estimated by PLBA, both reached similar peak dosages, similar dosage for IgG WSR antibody response, and comparable IgG WSR antibody levels, indicating that the WSR dose estimates based on RP were bioequivalent. The 9‐dosc HP regimen produced fewer late phase local and systemic reactions per patient than the 40‐dose HP regimen. Most patients experiencing severe systemic reactions were among those most skin sensitive to WSR. The number of systemic reactions per injection was significantly higher at higher WSR doses. One LP extract produced a high incidence of systemic reactions in the initial three injections. With respect to HP, its RP varied ∼ 10‐fold depending on the skin sensitivity of the patient to heat‐stable ragweed allergens, demonstrating that it was compositionally different. However, when the dose of this extract was estimated by RP based on the skin sensitivity of each patient, the peak dose of the extract as well as the doses associated with late phase and systemic reactions were found to be similar to the HP doses. This indicated that immunizing dose estimates of compositionally different WSR extracts based on RP by PLBA were also bioequivalent.
In Vitro Hepatitis B virus suppression of erythropoiesis is dependent on the multiplicity of infection and is reversible with anti-HBs antibodies
Authors: Jerome B. Zeldis, Francis A. Farraye, Howard N. Steinberg
Journal: Hepatology (1988)

Exposure of human bone marrow mononuclear cells to hepatitis B virus results in the suppression of the in vitro growth of several hematopoietic progenitor cells. We studied the degree of inhibition of erythroid progenitor cells that results as a function of the time of exposure of mononuclear cells to hepatitis B virus and the ratio of virus to mononuclear cells, the multiplicity of infection. With an overnight incubation of mononuclear cells with hepatitis B virus-containing sera, a multiplicity of infection of greater than one virus per mononuclear cell is required to observe significant inhibition of erythroid colony formation. This multiplicity of infection effect is also observed with purified Dane particles. Exposure of mononuclear cells to an increasing number of Dane particles results in a dose-dependent suppression of erythroid colony formation with significant inhibition observed with a multiplicity of infection of virus to mononuclear cells as low as 5:1. Murine monoclonal antibodies to HBsAg completely neutralize the hepatitis B virus-mediated inhibition of CFU-E while control antibodies do not. Purified HBsAg has no effect on colony formation. In conclusion, the hepatitis B virus-mediated inhibition of erythrogenesis in vitro provides a basis for understanding the bone marrow depression observed during hepatitis B virus infections and may provide an in vitro model for examining hepatitis B virus infection.
Gonorrhea in Women
Authors: Martin Hart
Journal: JAMA (1971)

Two hundred thirty-one female patients of private obstetricians and gynecologists were examined for gonorrhea, using cultural techniques. Specimens were taken from the cervix and rectum of all patients and cultured on Thayer-Martin (TM) selective medium. Six, or 2.6%, were found positive. Of these, all were in the 20- to 29-year age group; only one had knowledge of being exposed to gonorrhea; three were pregnant. The frequently asymptomatic nature of gonorrhea in females, combined with a definable incidence of infection in this patient group, suggests that more frequent use of cultural methods employing TM medium would help control this rapidly increasing disease. Cultures are particularly recommended for women under 30 years who are single, pregnant, or manifest acute vaginitis.
Role of sympathectomy for hyperhidrosis.
Authors: R M Greenhalgh, D S Rosengarten, P Martin
Journal: BMJ (1971)

Sweat glands are of two main types, eccrine and apocrine. Apocrine glands develop in association with hair follicles and play no part in thermor?gulation. They are distributed in the axilla, perineum, and mammary areola and secrete a milky odourless fluid, are probably under the control of circulating adrenaline, and do not appeau to be supplied by secretory nerves.1 On the other hand, eccrine glands are found throughout most of the skin?very dense on the palms and soles but less so in the head and neck, trunk, and upper arms and legs. They are situated deep in the dermis and secrete a dilute solution containing urea and lactic acid. The sodium chloride concentration varies according to the level of adrenocortical activity.2 Eccrine glands are important in ther mor?gulation, are supplied by cholinergic fibres present in sympathetic nerves, and are inhibited by atropine.
Antibody Inhibitors to von Willebrand Factor Metalloproteinase and Increased Binding of von Willebrand Factor to Platelets in Ticlopidine-Associated Thrombotic Thrombocytopenic Purpura
Authors: Han-Mou Tsai, Lawrence Rice, Ravindra Sarode, Thomas W. Chow, Joel L. Moake
Journal: Annals of Internal Medicine (2000)

Background: Thrombotic thrombocytopenic purpura (TTP) affects 1 in 1600 to 1 in 5000 patients who receive ticlopidine, but little is known about the pathogenesis of this complication. Objective: To investigate whether von Willebrand factor (vWF), which has been associated with idiopathic TTP, is involved in the pathogenesis of ticlopidine-associated TTP. Design: Case series. Setting: Three tertiary care, university-affiliated medical centers. Patients: Seven patients who developed TTP 2 to 7 weeks after initiation of ticlopidine therapy. Controls were 7 consecutive patients without thrombocytopenia who had been receiving ticlopidine for 3 to 5 weeks and 10 randomly selected hospitalized patients. Measurements: Platelet-bound vWF in patients' EDTA-anticoagulated whole blood samples; vWF proteinase activity in patients' plasma samples; inhibitory activity of IgG isolated from patients' plasma samples against the proteinase from the controls' plasma samples; and vWF multimeric patterns in patients' EDTA-anticoagulated plasma samples. Results: Binding of vWF to single platelets was increased in the three patients tested during the most thrombocytopenic phase of TTP episodes. Initial plasma samples from all seven patients lacked the largest vWF multimers and were severely deficient in vWF metalloproteinase. IgG molecules, isolated from plasma samples of five patients, inhibited metalloproteinase in plasma samples from the controls. In patients examined, these abnormalities resolved upon the remission that accompanied plasma exchange and discontinuation of ticlopidine therapy. Conclusion: In the patients who developed ticlopidine-associated TTP, autoantibodies to the vWF metalloproteinase were formed; this led to the same type of vWF abnormalities observed in patients with idiopathic acute TTP. The findings suggest that failure to process large and unusually large vWF multimers in vivo caused binding of vWF to platelets, systemic platelet thrombosis, and TTP.
Development of sports and exercise medicine in Ireland and future challenges
Authors: Philip E Carolan
Journal: British Journal of Sports Medicine (2011)

Lecture 25 The Faculty of Sports and Exercise Medicine was set up in September 2001 and is a joint Faculty of the Royal College of Physicians and Royal College of Surgeons in Ireland. The Medical Council gave the Speciality, Specialist recognition in May 2004 and to date there are 25 doctors on the Register of Medical Specialists in the Division of Sports and Exercise Medicine. The Faculty has developed a curriculum for Higher Specialist Training; this is a 4-year training programme which includes a number of core specialities that trainees must complete (ie, A&amp;E, Cardiology/Resp Medicine, etc). All trainees will have completed a BST programme and should have completed some Postgraduate course such as an MSc in Sports and Exercise Medicine (SEM). Our curriculum is very similar to FSEM (UK) HST training programme and both Faculties have collaborated over the curriculum development. Unfortunately we have not secured funding for a programme and trainees need to apply prospectively to the Faculty to outline there training programme rotations for accreditation. This has become more difficult for trainees with changes to the Irish Medical Council Register where trainees need to be in approved training numbered posts. We continue to work with the Medical Council, Health Service Executive and the Forum of Postgraduate Training Bodies. Part 11 of the Medical Practitioner Act 2007 was commenced in May 2010, bringing Competence Assurance into law, this will drive the need for a training programme and developing CPD programmes. Going forward, further development of Postgraduate programmes in SEM for doctors with a special interest in SEM is very important at either MSc or Diploma Level. The Faculty continue to work on developing continuous education programmes with a new Diploma course in conjunction with the Irish College of General Practice. E-learning programme development in conjunction with the NUI colleges should be explored. For development of the Speciality, UEMS recognition is a must with an agreed Specialist Training programme curriculum that can be delivered throughout Europe. I believe that both Faculties from Ireland and UK can collaborate on having a greater input on such developments.
Poland introduces partial ban on smoking in public places
Authors: N. Stafford
Journal: BMJ (2010)

Poland’s acting president, Bronislaw Komorowski, has signed a new law that bans smoking in many public places but that falls far short of the complete ban in public that supporters had wanted.

The bill, signed by Mr Komorowski, the parliamentary speaker who became acting president earlier this month after the plane crash in Russia that killed the president and other top government officials, was a compromise between bills approved by the Sejm, Poland’s lower chamber, and the Senate.

Lukasz Balwicki, of the department of public health and social medicine at the Medical University of Gdansk, told the BMJ that the new law will allow bars, restaurants, and workplaces with more than one room to set up a room for smoking, provided that it is closed and ventilated. Furthermore, operators of hotels, airports, universities, and elderly people’s homes have the option, but are …
The Effect of Cardiac Resynchronization on Morbidity and Mortality in Heart Failure
Authors: John G.F. Cleland, Jean-Claude Daubert, Erland Erdmann, Nick Freemantle, Daniel Gras, Lukas Kappenberger, Luigi Tavazzi
Journal: New England Journal of Medicine (2005)

Cardiac resynchronization reduces symptoms and improves left ventricular function in many patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. We evaluated its effects on morbidity and mortality.Patients with New York Heart Association class III or IV heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony who were receiving standard pharmacologic therapy were randomly assigned to receive medical therapy alone or with cardiac resynchronization. The primary end point was the time to death from any cause or an unplanned hospitalization for a major cardiovascular event. The principal secondary end point was death from any cause.A total of 813 patients were enrolled and followed for a mean of 29.4 months. The primary end point was reached by 159 patients in the cardiac-resynchronization group, as compared with 224 patients in the medical-therapy group (39 percent vs. 55 percent; hazard ratio, 0.63; 95 percent confidence interval, 0.51 to 0.77; P<0.001). There were 82 deaths in the cardiac-resynchronization group, as compared with 120 in the medical-therapy group (20 percent vs. 30 percent; hazard ratio 0.64; 95 percent confidence interval, 0.48 to 0.85; P<0.002). As compared with medical therapy, cardiac resynchronization reduced the interventricular mechanical delay, the end-systolic volume index, and the area of the mitral regurgitant jet; increased the left ventricular ejection fraction; and improved symptoms and the quality of life (P<0.01 for all comparisons).In patients with heart failure and cardiac dyssynchrony, cardiac resynchronization improves symptoms and the quality of life and reduces complications and the risk of death. These benefits are in addition to those afforded by standard pharmacologic therapy. The implantation of a cardiac-resynchronization device should routinely be considered in such patients.
Experimental systems for the study of hepadnavirus and hepatitis delta virus infections
Authors: William S. Mason, John M. Taylor
Journal: Hepatology (1989)

The past decade has seen a dramatic increase in the number of approaches available for the study of hepadnavirus and hepatitis delta virus infections. In this review, we have summarized the recent applications of these approaches to the study of virus replication, tissue specificity, liver injury and hepatocellular carcinogenesis.