tbuckley/cabot-search huggingface dataset:
Dignity is a useless concept
Authors: R. Macklin
Journal: BMJ (2003)

It means no more than respect for persons or their autonomy 

Appeals to human dignity populate the landscape of medical ethics. Claims that some feature of medical research or practice violates or threatens human dignity abound, often in connection with developments in genetics or reproductive technology. But are such charges coherent? Is dignity a useful concept for an ethical analysis of medical activities? A close inspection of leading examples shows that appeals to dignity are either vague restatements of other, more precise, notions or mere slogans that add nothing to an understanding of the topic.

Possibly the most prominent references to dignity appear in the many international human rights instruments, such as the United Nations' universal declaration of human rights.1 With few exceptions, these conventions do not address medical treatment or research. A leading exception is the Council of Europe's convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine.2 In this and other documents “dignity” seems to have no meaning beyond what is implied by the principle of medical ethics, respect for persons: the need to obtain voluntary, informed consent; the requirement to protect confidentiality; …
Treating hypertension: the evidence from clinical trials
Authors: J. A Simon
Journal: BMJ (1996)

cal resolution of major enignas, such as the largely unexplained differences in morbidity and mortality across socioeconomic groups."As I wrote in a letter to Science in response to Gary Taubes's article:7 "It could be said for epidemiology, with respect to disease etiology and prevention, what is frequently said about democracy as a system of government: they both have many problems and weaknesses, but they still represent the best available approach for the achievement of their respective objectives.
The use of the dermatoscope to identify early melanoma using the three-colour test
Authors: R.M. Mackie, C. Fleming, A.D. McMahon, P. Jarrett
Journal: British Journal of Dermatology (2002)

There is continuing interest in pre-operative evaluation of cutaneous pigmented lesions with the aim of differentiating early melanoma, which requires excision from non-melanomatous pigmented lesions that may safely be left untreated.To establish, in the setting of a specialist pigmented lesion clinic, if use of the hand-held dermatoscope can prevent unnecessary excision of benign melanocytic pigmented lesions.The study was carried out by three dermatologists experienced in the use of the dermatoscope. Patients had been referred by primary care physicians to the pigmented lesion clinic and had melanocytic lesions considered by dermatologists to merit excision on clinical grounds. A set of 74 sequentially observed lesions referred for excision, 37 melanomas and 37 melanocytic naevi, was used as the initial set and, thereafter, a second set of 52 lesions comprising 32 melanomas and 20 melanocytic naevi was used to validate conclusions drawn from the original set. Clinical features such as appearance and history, and also dermatoscope features were included in the assessment.In both sets of lesions, the most powerful identifying feature of lesions subsequently shown on pathological examination to be melanoma was the presence of three or more colours seen in the lesion on dermatoscopy. In the initial set of lesions, the age of the patient, an irregular edge and largest diameter of the lesion also contributed to diagnosis; however, in the second set of lesions these variables contributed little additional discriminatory value. The sensitivity and specificity of the three-colour dermatoscopy test for melanoma vs. naevus were 92% and 51%, respectively.The use of the dermatoscope three-colour test could reduce excision of benign melanocytic naevi by 50%, and thus prevent both unnecessary minor surgical workload and patient morbidity.
The Mutual Independence of the Endolymphatic Potential and the Concentrations of Sodium and Potassium in Endolymph
Authors: Saul W. Brusilow, Ellen Gordes
Journal: Journal of Clinical Investigation (1973)

The relationship between the endolymphatic potential (EP) and the sodium and potassium concentration gradients between endolymph and interstitial fluid was studied both by measuring the EP at varying concentrations of sodium and potassium in endolymph and by measuring the effect of a depressed EP on the concentrations of these cations. Ethacrynic acid was used in dogs to change the concentration of sodium and potassium (meq/liter) in endolymph from 5.8 and 148 to 134 and 24.3, respectively. No change in the EP accompanied these alterations. In a second series of experiments the EP was reduced from + 72 mV to + 31 mV for a mean duration of 20 min. No change in the concentration of sodium and potassium in endolymph was found during the period of reduced EP. These data suggest that there is little relationship between the EP and the sodium and potassium concentrations in endolymph.
Inherited genetic susceptibility to monoclonal B-cell lymphocytosis
Authors: Dalemari Crowther-Swanepoel, Tanguy Corre, Amy Lloyd, Gianluca Gaidano, Bianca Olver, Fiona L. Bennett, Chi Doughty, Daniela Toniolo, Federico Caligaris-Cappio, Paolo Ghia, Davide Rossi, Andy C. Rawstron, Daniel Catovsky, Richard S. Houlston
Journal: Blood (2010)
The Evaluation of Right Ventricular Performance Using Krypton-81m
Authors: H R HAM, A PIEPSZ, J VANDEVIVERE, M GUILLAUME, P GOETHALS, A LENAERS
Journal: Clinical Nuclear Medicine (1983)

The availability of krypton-81m suitable for intravenous injection provides an easy means for assessing right ventricular function. The superimposition of the other heart chambers does not constitute a problem. The activity in the left heart is negligible and the study can be performed in the right anterior oblique position to obtain optimal separation between the right atrium and the right ventricle. Lung activity is quite high and should be corrected before computing the right ventricular ejection fraction. This correction can be accomplished by performing Tc-99m MAA perfusion scintigraphy. The measurement of the right ventricular ejection fraction appears to be reproducible with very small inter-and intraobserver variability. Good quality phase and amplitude images can be obtained with such high count rates.
Evaluation of the intraepithelial lymphocyte count in the jejunum in childhood enteropathies.
Authors: J Mavromichalis, M J Brueton, A S McNeish, C M Anderson
Journal: Gut (1976)

Intraepithelial lymphocyte counts were evaluated in 131 jejunal mucosal biopsies taken from children with a small intestinal enteropathy arising from a variety of causes including coeliac disease, (untreated, after gluten withdrawal, and during subsequent challenge), giardiasis, cow's milk protein intolerance, and 'intractable diarrhoea'. The counts were compared with those from the biopsies of children referred for investigation but in whom no gastrointestinal disease was demonstrated and from healthy siblings of children with coeliac disease, investigated during a family study. Children with coeliac disease showed a raised count which fell after gluten withdrawal as has been demonstrated by others in adults. Lymphocytic infiltration of the epithelium increased rapidly during gluten challenge in such children, while no change was seen in those children proven ultimately not to have coeliac disease by the usually recognized criteria. In other enteropathies the range of counts was wide, overlapping with both normal and coeliac groups and indicating the nonspecificity of lymphocytic infiltration of the gut epithelium. The findings are discussed in relation to their significance and to further avenues of investigation to determine their possible diagnostic value in confirming the diagnosis of coeliac disease during gluten challenge.
Ontogeny of Ia and IgD on IgM-bearing B lymphocytes in mice.
Authors: J F Kearney, M D Cooper, J Klein, E R Abney, R M Parkhouse, A R Lawton
Journal: The Journal of Experimental Medicine (1977)

We used immunofluorescence to examine the developmental relationship of Ia and IgD on B cells. Pre-B cells in fetal liver did not express Ia. Only very few surface IgM-positive (sIgM+) B cells in fetal spleen were found to be Ia+ and were weakly stained for Ia. After birth there was a linear increase in the proportion of sIgM+ spleen cells which expressed Ia, reaching 95% by 9 days. Adult bone marrow also contains a sizeable proportion of sIgM+ Ia- cells. Unstimulated cells from fetal or newborn liver and spleen expressed Ia at the same rate in culture. Anti-Ia antisera suppressed the LPS-induced differentiation of IgM and IgG plasma cells in cultures of neonatal lymphocytes. Ia was also detected on IgM and IgG plasma cells in vitro suggesting that lipopolysaccharide (LPS)-stimulated B cells by may express Ia antigens, induced by LPS, or appearing as part of normal differentiation. IgD did not appear on sIgM+ cells until 3 days of age and then rose slowly to reach adult levels later than Ia antigens.
Should cases of permanent vegetative state still go to court?
Authors: B. Jennett
Journal: BMJ (1999)

Education and debate p 841 

Since the judgments in the Tony Bland case in 1993 it has been necessary to obtain high court approval before withdrawing artificial nutrition and hydration from a patient in a permanent vegetative state. There have been 18 cases in England and one in Scotland, and in this issue Wade and Johnston review the medical and legal procedures involved (p 841).1 A consensus exists in many countries that such treatment withdrawal is medically, morally, and legally appropriate, but only in the United Kingdom is a court appearance required before this can be done.2 May it not be time to change this practice?

In the Bland case the Master of the Rolls and four of the five judges in the House of Lords indicated that their recommendation that future cases should each come to court was to be an interim measure until a …
Hepatic extraction of organic anions in the rat depends on ligand hydrophobicity
Authors: Hironori Tokumo, Nankei Aoyama, Norbert Busch, Daniel J. Mancuso, Holzbach R. Thomas
Journal: Hepatology (1991)

Non-bile-salt cholephilic organic anions are efficiently taken up by the liver. Recent work from our group has suggested the possible importance of relative hydrophobicity among various organic anions in hepatic uptake. To further validate and clarify this, we studied hepatic extraction of five different cholephilic dyes using the isolated perfused rat liver in single-pass mode. Albumin binding affinities and capacities for each of the ligands were measured in vitro to permit evaluation of in vivo interactions for each of them over a spectrum of unbound ligand concentrations. As expected, a strong positive correlation was found between ligand hydrophobicity and the relative degree of albumin binding affinity and capacity. Using appropriate experimental conditions, we also found a strong positive correlation between hepatic extraction efficiency for a given ligand and both its hydrophobicity and its unbound concentration. These data indicate that where the unbound ligand concentration is significant, the greater the ligand hydrophobicity, the greater is its efficiency of hepatic extraction. We conclude that hepatic extraction efficiency for non-bile-salt cholephilic organic anions depends on a combination of ligand hydrophilic/hydrophobic balance and the availability of the unbound ligand for uptake.
Interferon-alpha and interleukin 2 synergistically enhance basic fibroblast growth factor synthesis and induce release, promoting endothelial cell growth.
Authors: F Cozzolino, M Torcia, M Lucibello, L Morbidelli, M Ziche, J Platt, S Fabiani, J Brett, D Stern
Journal: Journal of Clinical Investigation (1993)

To elucidate mechanisms underlying neovascularization that accompanies certain chronic immune/inflammatory disorders, the effects of interferon-alpha (IFN-alpha) and interleukin 2 (IL-2) on endothelial cell (EC) growth in vitro and angiogenesis in vivo were studied. Preincubation of cultured human ECs with IFN-alpha, followed by exposure to IL-2, resulted in effective stimulation of cell growth, whereas either cytokine alone had only a slight effect. The combination of IFN-alpha/IL-2 induced an angiogenic response in the rabbit cornea. IL-2 receptor expression was enhanced on IFN-alpha-treated ECs: p55 was increased and p70 was induced. 125I-IL-2 binding to ECs treated with IFN-alpha was enhanced (Kd from approximately 7 nM to approximately 260 pM with IFN-alpha), and anti-p55 IgG blocked 125I-IL-2/EC interaction as well as IL-2-mediated EC proliferation. Consistent with these findings in cell culture, immunohistologic studies demonstrated p55 and p70 antigen in the vasculature of rheumatoid joints, but not in normal joint tissue. Exposure of cultured ECs to IFN-alpha increased levels of intracellular EC basic fibroblast growth factor (bFGF), and subsequent addition of IL-2 led to bFGF release into the medium. The observation that anti-bFGF IgG largely blocked EC proliferation in response to IFN-alpha/IL-2 suggested that bFGF was a critical agent in this setting. These data suggest a mechanism rendering ECs responsive to IL-2 which may be relevant in immune/inflammatory disorders: IFN-alpha-mediated induction of functional EC receptors for IL-2, which drives cell proliferation by a mechanism dependent on increased synthesis and release of bFGF.
Liposome-mediated transfection of intact viral particles reveals that plasma membrane penetration determines permissivity of tissue culture cells to rotavirus.
Authors: D M Bass, M R Baylor, C Chen, E M Mackow, M Bremont, H B Greenberg
Journal: Journal of Clinical Investigation (1992)

Rotaviruses are an important cause of gastroenteritis in human infants. In vivo, rotavirus displays striking cell tropism with viral replication generally restricted to the villus tip enterocytes of the small intestine. We studied a panel of cell lines that vary significantly in their permissivity to rotavirus infection. L cells and HEp2 cells were relatively resistant to rotavirus infection compared with permissive Ma104 cells and HT29 cells. RNA transcription among the cell lines was proportional to antigen synthesis making a translational or posttranslational block an unlikely source of observed differences in susceptibility. All of the cell lines bound and internalized radiolabeled virus equally well, as measured by escape from surface protease treatment. Analysis of the escape of cell bound virus from neutralizing monoclonal antibody revealed that rotavirus did not immediately enter an eclipse phase in nonpermissive cells, but was internalized in an infectious form for several hours, possibly sequestered within endocytic vacuoles. L cells and HEp2 cells were as permissive as Ma104 and HT29 cells when rotavirus infection was mediated by transfection of single- or double-shelled rotavirus particles with cationic liposomes (Lipofectin). Rotavirus cell tropism in tissue culture cells is determined by the ability of infecting virions to traverse the plasma membrane of the cells into the cytoplasmic compartment.
Frida Kahlo de Rivera Symposium
Authors: John R. F. Penido
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Upon returning from a recent trip to Mexico, I am faced with the reproduction of the painting, "The Two Fridas," by Frida Kahlo on the cover of the Sept 16 issue ofThe Journal. I must confess when I first saw the painting at the Frida Kahlo Museum in Mexico, being also a cardiovascular surgeon, I thought of the cross circulation of Lillehei. However, next to the painting there is a long explanation by the artist for the reason for this painting and, contrary to our original interpretation, the artist is portraying the existence of another Frida in her subconscious. She relates this in great detail in her personal diary, and pages of the diary are reproduced for the visitor. The artist relates to conversation and visits with this second girl, "much like herself," and is unable to explain the existence of this other being. The Frida
Antibodies to Renin as Proof of the Pathogenesis of Sustained Renal Hypertension
Authors: GEORGE E. WAKERLIN
Journal: Circulation (1958)

Antirenin to hog renin produced in the dog neutralizes the acute pressor effect of dog as well as hog renin. A course of intramuscular injections of hog renin in chronic renal hypertensive dogs produces an antihypertensive effect which is correlated with the antirenin titers of the plasma. Passive transfer of high titer homologous antiserum to hog renin produces an antihypertensive effect in chronic renal hypertensive dogs which is correlated with the antirenin titer. The results suggest a pathogenetic role for renin in experimental renal hypertension in the dog.
Haldane, hot dogs, halitosis, and hypoxic vasodilation: the emerging biology of the nitrite anion
Authors: Mark T. Gladwin
Journal: Journal of Clinical Investigation (2004)

While it has long been known that the reduction of nitrite to nitric oxide (NO) forms iron-nitrosyl-myoglobin and is the basis of meat curing, a greater biological activity of the nitrite anion has only recently been appreciated. In the stomach, NO is formed from acidic reduction of nitrite and increases mucous barrier thickness and gastric blood flow (see the related study beginning on page 106). Nitrite levels in blood reflect NO production from endothelial NO synthase enzymes, and recent data suggest that nitrite contributes to blood flow regulation by reaction with deoxygenated hemoglobin and tissue heme proteins to form NO.
BMJ pico for original research in the print BMJ
Authors: T. Groves, S. Schroter
Journal: BMJ (2009)

<h3>Introduction</h3> Gestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps. <h3>Methods and analysis</h3> MEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD. <h3>Ethics and dissemination</h3> All IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.
Identification of four chromosomal loci determining obesity in a multifactorial mouse model.
Authors: C H Warden, J S Fisler, S M Shoemaker, P Z Wen, K L Svenson, M J Pace, A J Lusis
Journal: Journal of Clinical Investigation (1995)

We previously described a new mouse model for multigenic obesity, designated BSB. We now report the use of a complete linkage map approach to identify loci contributing to body fat and other traits associated with obesity in this model. Four loci exhibiting linkage with body fat, or with the weights of four different fat depots, residing on mouse chromosomes 6, 7, 12, and 15, were identified and confirmed by analysis of additional BSB mice. Each of the four loci differed with respect to their effects on the percent of body fat, specific fat depots and plasma lipoproteins. The loci exhibited allele-specific, non-additive interactions. A locus for hepatic lipase activity was co-incident with the body fat and total cholesterol loci on chromosome 7, providing a possible mechanism linking plasma lipoproteins and obesity. The chromosome 7 locus affecting body fat, total cholesterol and hepatic lipase activity was isolated in congenic strains whose donor strain regions overlap with the chromosome 7 BSB locus. These results provide candidate genes and candidate loci for the analysis of human obesity.
Many cord blood banks' claims are unfounded, says royal college
Authors: Lynn Eaton
Journal: BMJ (2006)

Saving umbilical cord blood from newborn babies in commercial banks for use later in life is unnecessary and its benefit is unproved, a leading UK committee has reported.

The Scientific Advisory Committee of the Royal College of Obstetricians and Gynaecologists gave this finding in updating its advice on umbilical cord blood banking, which was first issued in 2001. Since then the number of private banks operating in Europe has grown.

Doctors had approached the college asking for advice on the safety of such banks and whether the claims being made by the private banks-such as that their services were “like freezing a spare immune system”—were valid.

Peter Braude, chairman of the committee, said the committee wholeheartedly supported the collection of stem cells from the umbilical cord when babies were at high risk of diseases such as aplastic anaemia, immunodeficiency syndromes, congenital erythroblastopenia, sickle cell anaemia, and thalassaemia. The NHS's Cord Blood Bank …
Unraveling Insulin-Like Growth Factor Binding Protein-3 Actions in Human Disease
Authors: Sherryline Jogie-Brahim, David Feldman, Youngman Oh
Journal: Endocrine Reviews (2009)

The IGF system plays critical roles in somatic growth in an endocrine fashion (somatomedin hypothesis) as well as proliferation and differentiation of normal and malignant cells in a paracrine/autocrine fashion. IGFBP-3 is known to modulate the actions of IGFs in circulation as well as the immediate extracellular environment. Interestingly, apart from the ability to inhibit or enhance IGF actions, IGFBP-3 also exhibits very clear, distinct biological effects independent of the IGF/IGF-I receptor axis. Over the past decade it has become widely appreciated that IGF/IGF-IR-independent actions of IGFBP-3 (antiproliferative and proapoptotic effects) contribute to improving the pathophysiology of a variety of human diseases, such as cancer, diabetes, and malnutrition. Recent studies have implicated interaction of IGFBP-3 with a variety of proteins or signaling cascades critical to cell cycle control and apoptosis; however, the actual mechanism of IGFBP-3 action is still unclear. This review reinforces the concept in support of the IGF/IGF-IR axis-independent actions of IGFBP-3 and delineates potential underlying mechanisms involved and subsequent biological significance, focusing in particular on functional binding partners and the clinical significance of IGFBP-3 in the assessment of cancer risk.