tbuckley/cabot-search huggingface dataset:
From optimism to disillusion about commitment to transparency in the medico-industrial complex
Authors: I. Chalmers
Journal: Journal of the Royal Society of Medicine (2006)

But then we thought, ‘What about trials that don’t get published? If we don’t take those into account, we might reach biased conclusions’. We knew of anecdotes about researchers who had had disappointing results of trials, and had therefore never made the results public. Furthermore, in an important analysis of controlled trials of treatments for cancer of the ovary published in 1986, an Australian oncologist, John Simes, had shown how failure to publish clinical trials could lead to misleading inferences about the effects of treatments. 2 So we wrote to 42 000 obstetricians, paediatricians and other clinicians around the world to try to flush out information about studies that had been done but had never been reported. It was an almost complete waste of time; we published our experience to warn others to think carefully before using the retrospective survey approach we had used in our attempt to deal with publication bias.3 Like John Simes before us, we concluded that a prerequisite for tackling the problem of biased underreporting of research involved registering controlled trials publicly, at inception, before their results could influence whether or not the world would come to know about them. In 1990, based on a paper I had presented at the 1st Congress on Peer Review in Biomedical Publishing, I published an article with the deliberately provocative title ‘Underreporting research is scientific misconduct’. I suggested that failing to report well-conducted clinical trials was not only scientific misconduct, but also unethical; it broke an implicit contract with the patients who had
Immune monitoring technology primer: immunosequencing
Authors: Ilan Kirsch
Journal: Journal for ImmunoTherapy of Cancer (2015)

Profiling of the immune receptor repertoire is becoming increasingly relevant to the understanding and clinical management of cancer, autoimmunity, aging, and infectious disease.A platform technology is described that provides comprehensive immune receptor profiling.Immunosequencing is a platform technology that allows the enumeration, specification and quantification of each and every B-and/or T-cell in any biologic sample of interest. It is based on bias-controlled multiplex PCR and high throughput sequencing and is highly accurate, standardized, and sensitive.
Working toward immune tolerance in lung transplantation
Authors: Xinguo Jiang, Mark R. Nicolls
Journal: Journal of Clinical Investigation (2014)

Long-term allograft survival is a major challenge facing solid organ transplantation. Recent studies have shown a negative correlation between infiltration of memory T cells and allograft survival. Furthermore, blockade of leukocyte activation increases acceptance of transplanted organs, including heart, liver, and kidney. Lung allografts are associated with high rates of rejection, and therapies that increase acceptance of other transplanted organs have not translated into the lung. In this issue of the JCI, Krupnick and colleagues demonstrate in a murine model that lung allograft acceptance requires infiltration of a specific T cell population into the graft. This study highlights the unique immunobiology of the lung and the complexity of lung transplant tolerance.
Usefulness of Electron Beam Tomography in Adolescents and Young Adults With Heterozygous Familial Hypercholesterolemia
Authors: Samuel S. Gidding, Lisa C. Bookstein, Eva V. Chomka
Journal: Circulation (1998)

Background —Because of the success of secondary prevention of coronary events by intense risk factor modification, a more precise measure of atherosclerosis in youth would have great clinical value both in the design of clinical trials for the demonstration of the usefulness of coronary disease prevention early in life and in guiding therapy. Identification of calcium in coronary arteries by electron beam tomography has been associated with severity of atherosclerosis in adults. Methods and Results —Twenty-nine youths 11 to 23 years old with familial hypercholesterolemia (average LDL cholesterol, 5.95 mmol/L) underwent electron beam tomography as well as comprehensive risk factor assessment with measurement of total cholesterol, triglycerides, HDL cholesterol, lipoprotein (a), apolipoprotein E phenotype, blood pressure, body mass index, and history of tobacco use. Significant coronary calcium was identified in 7 of 29 subjects. Increased body mass index was significantly associated with the presence of coronary calcium (25.3 versus 20.6 kg/m 2 , P &lt;0.03). No other risk factors were associated with the presence of coronary calcium. Conclusions —Coronary calcium, uncommonly identified before the fourth decade, was found in a significant percentage of adolescents and young adults with familial hypercholesterolemia. Overweight may increase the likelihood of coronary calcium being present in individuals already at high risk.
Nutrition and sickle cell disease
Authors: John David Reed, Rupa Redding‐Lallinger, Eugene P. Orringer
Journal: American Journal of Hematology (1987)

The role of protein and calorie deficiency in sickle cell disease remains poorly defined. While such features as growth retardation, impaired immune function, and delayed menarche do suggest a relationship between sickle cell disease and undernutrition, measurement of more direct nutritional parameters in these patients have yielded mixed results. Anthropometric measurements such as skinfold thickness are subnormal in many but not all reports. Serum protein levels are normal, but low values for serum lipids have been reported. Finally, one small study shows an improvement in both growth parameters and clinical course following caloric supplementation. A variety of micronutrient deficiencies have been suggested in sickle cell disease. Numerous case reports describing an exacerbation of the chronic anemia that was reversed by folic acid therapy led to routine folate supplementation. More recent studies have shown, however, that clinically significant folic acid deficiency occurs only in a small minority of sickle cell patients. Clearly, more work is necessary to define the cost/benefit ratio of routine folic acid supplementation. Pharmacological amounts of vitamin B6 and certain of its derivatives possess in vitro antisickling activities. Nevertheless, a small clinical trial failed to demonstrate any consistent hematologic effects of B6 supplementation. Several reports indicate that vitamin E levels are low in sickle erythrocytes. Since these abnormal red cells both generate excessive oxidation products and are more sensitive to oxidant stress, and because oxidants appear to play a role in ISC formation, vitamin E deficiency could well be linked to ISC formation and hemolysis. Small clinical trials, however, have again failed to produce a clear hematological response in sickle cell anemia. The role of zinc in sickle cell disease has received considerable attention. Though studies are generally small, most do support a relationship between sickle cell disease and zinc deficiency. Etiologic associations between zinc deficiency and such complications of sickle cell disease as poor ulcer healing, growth retardation, delays in sexual development, immune deficiencies, and high ISC counts have all been suggested. Most of these studies need further corroboration. Iron deficiency is now known to be a relatively common occurrence in sickle cell anemia, especially in children and pregnant women. The theoretical benefits of concomitant iron deficiency and sickle cell anemia remain to be proven in a controlled clinical trial.(ABSTRACT TRUNCATED AT 400 WORDS)
Self-experimentation and self-management: Allies in combination therapies
Authors: Irene Grote
Journal: Behavioral and Brain Sciences (2004)

Self-experimentation is a valuable companion to self-management in the benefit of pharmaco-cognitive-behavior combination therapies. However, data on individuals participating as active therapeutic agents are sparse. Smoking cessation therapy is an example. Roberts' self-experimentation suggests trying more diversity in research to generate new ideas. This may inform current approaches to the cessation of smoking.
Transfer factor for carbon monoxide in patients with diabetes with and without microangiopathy.
Authors: D C Weir, P E Jennings, M S Hendy, A H Barnett, P S Burge
Journal: Thorax (1988)

The transfer coefficient (KCO) was significantly lower in diabetic patients with microangiopathy than in a matched group without this complication. This may reflect microangiopathy in the pulmonary circulation.
Reduction of atrial natriuretic factor circulating levels by endogenous sympathetic activation in hypertensive patients.
Authors: M Volpe, N DeLuca, S A Atlas, M J Camargo, C Indolfi, G Lembo, B Trimarco, M Condorelli, J H Laragh
Journal: Circulation (1988)

The effects of endogenous activation of sympathetic nervous system on systemic and regional hemodynamics and on plasma levels of atrial natriuretic factor (ANF) were studied in subjects with essential hypertension. Stimulation of sympathetic nervous system was reflex-induced by a selective deactivation of carotid baroreceptors obtained by increasing external neck-tissue pressure (NTP) by means of a neck chamber. The effects of graded levels (+30, +45, and +60 mm Hg) and one single and sustained level (+45 mm Hg for 15 min) of NTP were studied. As expected, NTP caused reflex increases in blood pressure, heart rate, and forearm vascular resistance, whereas atrial pressures did not change significantly and cardiac output tended to increase. In the studies based on graded levels of NTP, immunoreactive ANF (irANF) progressively fell (from 31.7 +/- 10 to 13.3 +/- 4 fmol/ml; p less than .05) and the changes in irANF were significantly correlated with those observed in FVR (r = -.671, p less than .001). Both hemodynamic and irANF changes were prevented by adrenergic blockade (phentolamine + propranolol). During +45 mm Hg NTP for 15 min, the levels of irANF fell both in the pulmonary artery and in the inferior vena cava. The irANF arteriovenous difference also fell during this maneuver. These data show that, in hypertensive patients, factors other than atrial wall tension may influence ANF release. They also show that endogenous sympathetic activation may reduce ANF release.
Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study
Authors: Tayfun Güngör, Pierre Teira, Mary Slatter, Georg Stussi, Polina Stepensky, Despina Moshous, Clementien Vermont, Imran Ahmad, Peter J Shaw, José Marcos Telles da Cunha, Paul G Schlegel, Rachel Hough, Anders Fasth, Karim Kentouche, Bernd Gruhn, Juliana F Fernandes, Silvy Lachance, Robbert Bredius, Igor B Resnick, Bernd H Belohradsky, Andrew Gennery, Alain Fischer, H Bobby Gaspar, Urs Schanz, Reinhard Seger, Katharina Rentsch, Paul Veys, Elie Haddad, Michael H Albert, Moustapha Hassan
Journal: The Lancet (2013)
Heterogeneous expression of connexins in rabbit sinoatrial node cells: correlation between connexin isotype and cell size
Authors: H Honjo
Journal: Cardiovascular Research (2002)

Objective: Intercellular coupling through gap junctions allows the morphologically and functionally heterogeneous sinoatrial node to synchronize and drive the atrial muscle. The purpose of this study was to identify the connexin isotypes expressed by sinoatrial node cells and to analyse the density of connexins in relation to cell size. Methods: Labeling for the different connexins using isotype-specific antibodies was assessed in cells isolated from the rabbit sinoatrial node by immunoconfocal microscopy. Results: Sinoatrial node cells with a cell projection area smaller than 800 μm2 were devoid of immunolabeling for connexin43. Such small cells showed high levels of connexin45 labeling (compared to that in large cells) and low levels of connexin40 labeling. Sinoatrial node cells with a projection area between 800 and 1200 μm2 had a lower amount of connexin45 label and again a small amount of connexin40 but an increased amount of connexin43 label. In the larger sinoatrial node cells, some colocalization of connexin45 and connexin43 immunolabeled spots was observed. Conclusions: Rabbit sinoatrial node cells are heterogeneous in terms of connexin expression, and there is a clear cell size-dependence in pattern of connexin expression. Small (putative central) cells express connexin45 but not connexin43, whereas larger (putative peripheral) cells express both connexin45 and connexin43. The co-localization of connexin43 and connexin45 in larger cells raises the possibility that heterotypic or heteromeric connexin43/connexin45 channels could be present in gap junctions at the periphery of the sinoatrial node.
Homeostasis-Stimulated Proliferation Drives Naive T Cells to Differentiate Directly into Memory T Cells
Authors: Bryan K. Cho, Varada P. Rao, Qing Ge, Herman N. Eisen, Jianzhu Chen
Journal: The Journal of Experimental Medicine (2000)

The developmental requirements for immunological memory, a central feature of adaptive immune responses, is largely obscure. We show that as naive CD8 T cells undergo homeostasis-driven proliferation in lymphopenic mice in the absence of overt antigenic stimulation, they progressively acquire phenotypic and functional characteristics of antigen-induced memory CD8 T cells. Thus, the homeostasis-induced memory CD8 T cells express typical memory cell markers, lyse target cells directly in vitro and in vivo, respond to lower doses of antigen than naive cells, and secrete interferon γ faster upon restimulation. Like antigen-induced memory T cell differentiation, the homeostasis-driven process requires T cell proliferation and, initially, the presence of appropriate restricting major histocompatibility complexes, but it differs by occurring without effector cell formation and without requiring interleukin 2 or costimulation via CD28. These findings define repetitive cell division plus T cell receptor ligation as the basic requirements for naive to memory T cell differentiation.
The relationship between arrhythmogenesis and impaired contractility in heart failure: role of altered ryanodine receptor function
Authors: Andriy E. Belevych, Dmitry Terentyev, Radmila Terentyeva, Yoshinori Nishijima, Arun Sridhar, Robert L. Hamlin, Cynthia A. Carnes, Sandor Györke
Journal: Cardiovascular Research (2011)

In heart failure (HF), abnormal myocyte Ca2+ handling has been implicated in cardiac arrhythmias and contractile dysfunction. In the present study, we investigated the relationships between Ca2+ handling, reduced myocyte contractility, and enhanced arrhythmogenesis during HF progression in a canine model of non-ischaemic HF. Key Ca2+ handling parameters were determined by measuring cytosolic and intra-sarcoplasmic reticulum (SR) [Ca2+] in isolated ventricular myocytes at different stages of HF. The progression of HF was associated with an early and continuous increase in ryanodine receptor (RyR2)-mediated SR Ca2+ leak. The increase in RyR2 activity was paralleled by an increase in the frequency of diastolic spontaneous Ca2+ waves (SCWs) in HF myocytes under conditions of β-adrenergic stimulation. In addition to causing arrhythmogenic-delayed afterdepolarizations, SCWs decreased the amplitude of subsequent electrically evoked Ca2+ transients by depleting SR Ca2+. At late stages of HF, Ca2+ release oscillated essentially independent of electrical pacing. The increased propensity for the generation of SCWs in HF myocytes was attributable to reduced ability of the RyR2 channels to become refractory following Ca2+ release. The progressive alterations in RyR2 function and Ca2+ cycling in HF myocytes were associated with sequential modifications of RyR2 by CaMKII-dependent phosphorylation and thiol oxidation. These findings suggest that destabilized RyR2 activity due to excessive CaMKII phopshorylation and oxidation resulting in impaired post-release refractoriness is a common mechanism involved in arrhythmogenesis and contractile dysfunction in the failing heart.
Lung cancer in patients with idiopathic pulmonary fibrosis
Authors: J. Park, D.S. Kim, T.S. Shim, C-M. Lim, Y. Koh, S.D. Lee, W.S. Kim, W.D. Kim, J.S. Lee, K.S. Song
Journal: European Respiratory Journal (2001)

Idiopathic pulmonary fibrosis (IPF) was reported to be associated with increased risk of lung cancer as a result of the occurrence of atypical or dysplastic epithelial changes in fibrosis which progressed to invasive malignancy. In that situation, the cancer will develop in the area of major fibrosis. To investigate the direct relationship between fibrosis and cancer development, the real concordance rate of the two lesions in the chest computed tomography (CT) was analysed and compared to the histological types of lung cancer. The subjects included 63 patients with combined lung cancer and IPF (IPF-CA), 218 patients with lone IPF, and 2,660 patients with primary lung cancer. All patients were diagnosed at Asan Medical Center during the same period. The age, percentage of smokers, and the male sex were significantly higher in IPF-CA compared with lone IPF. The odds ratio of smoking was 2.71 compared to nonsmoking IPF controls. In IPF-CA, 56% of the cancer was located in the periphery of the lung and 52% in the upper lobe. The majority of the cancers (64%) were found in the nonfibrotic area at chest CT. The most frequent cell type was squamous cell carcinoma (35%), and there was no significant difference in the cancer cell type between IPF-CA and total lung cancer population. These findings suggest that in combined lung cancer and idiopathic pulmonary fibrosis patients, the features of the lung cancer are similar to the total lung cancer population.
Polypoid lesions of the gall bladder Reply
Authors: C D JOHNSON, C. SATO
Journal: Gut (1997)

Editor,—The paper by Moriguchi et al (Gut 1996; 39: 860–2) raises a number of questions. The authors state that this is the first study to describe the natural history of these lesions, but their solitary conclusion, that most polypoid lesions of the gall bladder detected by ultrasonography are benign, is not new. Indeed, they seem to underestimate the risk of malignancy compared with other larger series.

Yang et al  1 studied 182 patients who underwent cholecystectomy and who had an ultrasonographic or pathological diagnosis of polypoid lesions of the gall bladder. There were 10 false positive ultrasound diagnoses. All the lesions …
An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD)
Authors: G Boyd, AH Morice, JC Pounsford, M Siebert, N Peslis, C Crawford
Journal: European Respiratory Journal (1997)

The objectives of this study were to compare the efficacy and safety of salmeterol xinafoate (50 and 100 microg b.i.d.) with that of placebo, when added to existing therapy, in the treatment of patients with chronic obstructive pulmonary disease (COPD). Six hundred and seventy four patients were randomized to receive either salmeterol 50 microg b.i.d., salmeterol 100 microg b.i.d., or placebo treatment for a period of 16 weeks. The results showed a significant improvement in daily symptom scores noted for patients taking either 50 microg (p=0.043) or 100 microg b.i.d. salmeterol (p=0.01) compared with placebo, with a corresponding decrease in additional daytime salbutamol requirements for both salmeterol groups. The same pattern was reflected for night-time symptoms and additional salbutamol use. During treatment, forced expiratory volume in one second (FEV1) measurements improved significantly in each salmeterol group, with up to a 7% improvement observed at the end of the study. Although no difference was observed between treatment groups for the distance walked in 6 min, patients treated with salmeterol 50 microg b.i.d. were significantly less breathless than those treated with placebo after their 6 min walk, after 8 weeks (p=0.024) and 16 weeks (p=0.004) of therapy. Adverse events were similar in all three groups except for tremor, which was significantly higher in the 100 microg b.i.d. salmeterol group (p=0.005) compared both with 50 microg b.i.d. salmeterol and placebo. Salmeterol offered further positive improvement to the effect of therapy in patients with chronic obstructive pulmonary disease when added to their existing regimens. This clinical improvement was similar both with 50 and 100 microg b.i.d. dosage, although the group receiving 50 microg b.i.d. tolerated the drug better than those receiving 100 microg b.i.d. salmeterol.
A doctor and a poet
Authors: Theodore Dalrymple
Journal: BMJ (2007)

I once met the doctor and poet Dannie Abse on a train. There is no reason why he should remember me, because I am not particularly memorable, but I was very impressed by him. The first volume of his autobiography, A Poet in the Family , is exquisitely written; and if I were dean of a medical school I would make all my students read it. Perhaps it is just as well that I am not dean of a medical school.

One has to be a doctor to appreciate fully some of the lines of Abse's poetry. Describing, for example, a bedroom in a Holiday Inn, one of those faceless hotels that transform Tegucigalpa into Wigan and vice …
Toxicity of Parathyroid Hormone in Uremia
Authors: S Klahr, E Slatopolsky
Journal: Annual Review of Medicine (1986)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More