tbuckley/cabot-search huggingface dataset:
P.T.A.P.: Determination of Essential Lf Dosage
Authors: G. Bousfield, L. B. Holt
Journal: BMJ (1950)

BDcLJOURNAL 73 chest wall.His pain was relieved immediately by this opera- tion, and, should it recur, treatment by percussion is now much more likely to be successful, as the neuromata are easily reached.In conclusion it should be emphasized that treatment by percussion has not on any occasion in our experience done harm.In some cases benefit has been apparent almost from the first treatment, but in others considerable perseverance has been required to get the desired relief. SummaryThe treatment of painful amputation stumps by repeated percussion to the neuromata has proved successful in most cases.Of 33 cases considered suitable for percussion treatment, 19 reported good or excellent results and 5 were improved.There was only one failure in the first 15 cases treated, but in the last 18 cases, some of which were especially difficult, there have been eight apparent failures.Methods of applying the treatment are described.The neuromata are located as accurately as possible.If they are very tender the arterial supply to the stump is occluded by a sphygmomanometer cuff, as anoxaemia renders them less sensi- tive.Percussion is done with a mallet and an applicator about 15 cm.long.After several minutes the cuff is removed and percussion continued for 20 minutes.An electrical vibrator may be used in place of the mallet, and is of particular value in treating areas beyond thq patient's reach.Cases with cold and diffusely tender stumps should be treated by sympathetic block or section rather than percussion.Illustrative case histories are given.We are specially indebted to Dr. E. J. H
Angiographic findigs and prognostic indicators in patients resuscitated from sudden cardiac death.
Authors: W D Weaver, G S Lorch, H A Alvarez, L A Cobb
Journal: Circulation (1976)

Sixty-four patients with coronary artery disease (CAD) who had been resuscitated from out-of-hospital ventricular fibrillation (VF) underwent cardiac catheterization and angiography. The majority (72%) had a previous history of cardiovascular disease; in the remaining 28%, VF was the first manifestation of CAD. Advanced coronary atherosclerosis was a common finding; 94% of the patients had severe stenoses (70% or greater diameter narrowing) in one or more of the major coronary arteries, and most (70%) had ventricular wall contraction abnormalities. In over half of the patients, coronary anatomy was potentially suitable for complete revascularization. During an average follow-up period of 20.4 months, fourteen of the 64 patients developed a second episode of VF and/or died suddenly (VF/SD). In an attempt to identify characteristics which might be of prognostic value, the clinical, hemodynamic, and angiographic characteristics of this group were compared to those patients who had a single episode of VF and survived during follow-up. Patients who developed recurrent VF/SD had more triple vessel CAD (P less than 0.01), lower ejection fractions (P less than 0.05), and far more severe abnormalities of left ventricular contraction (P less than 0.001). These results indicate that angiographic findings can identify individuals at high risk for recurrent VF and also suggest that myocardial scarring may be an important factor in the initiation of ventricular fibrillation and in its recurrence.
Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers
Authors: Nanda Horeweg, Ernst Th Scholten, Pim A de Jong, Carlijn M van der Aalst, Carla Weenink, Jan-Willem J Lammers, Kristiaan Nackaerts, Rozemarijn Vliegenthart, Kevin ten Haaf, Uraujh A Yousaf-Khan, Marjolein A Heuvelmans, Erik Thunnissen, Matthijs Oudkerk, Willem Mali, Harry J de Koning
Journal: The Lancet Oncology (2014)
The B1-agonist [des-Arg10]-kallidin activates transcription factor NF-kappaB and induces homologous upregulation of the bradykinin B1-receptor in cultured human lung fibroblasts.
Authors: J P Schanstra, E Bataillé, M E Marin Castaño, Y Barascud, C Hirtz, J B Pesquero, C Pecher, F Gauthier, J P Girolami, J L Bascands
Journal: Journal of Clinical Investigation (1998)

The bradykinin B1-receptor is strongly upregulated under chronic inflammatory conditions. However, the mechanism and reason are not known. Because a better understanding of the mechanism of the upregulation will help in understanding its potential importance in inflammation, we have studied the molecular mechanism of B1-receptor upregulation in cultured human lung fibroblasts (IMR 90) in response to IL-1beta and the B1-agonist [des-Arg10]-kallidin. We show that treatment of human IMR 90 cells by IL-1beta stimulates the expression of both B1-receptor mRNA and protein. The latter was studied by Western blot analysis using antipeptide antibodies directed against the COOH-terminal part of the human B1-receptor. We furthermore report the novel observation that the B1-receptor is upregulated by its own agonist which was completely blocked by the specific B1-antagonist [des-Arg10-Leu9]-kallidin, indicating an upregulation entirely mediated through cell surface B1-receptors. The increased population of B1-receptors was functionally coupled as exemplified by an enhancement of the B1-agonist induced increase in free cytosolic calcium. Upregulation by the B1-agonist was blocked by a specific protein kinase C inhibitor. B1-agonist-induced upregulation was correlated to the induction of transcription factor nuclear factor kappaB (NF-kappaB) which efficiently bound to the NF-kappaB-like sequence located in the promoter region of the human B1-receptor gene. This correlation was further confirmed by reporter gene assays which showed that this NF-kappaB-like sequence, in the B1-receptor promoter context, could contribute to IL-1beta and DLBK-induced B1-receptor transcription activation, and by the effect of NF-kappaB inhibitor pyrrolidinedithiocarbamate which diminished both B1-receptor upregulation and NF-kappaB activation. NF-kappaB is now recognized as a key inflammatory mediator which is activated by the B1-agonist but which is also involved in B1-receptor upregulation.
Old whines and new battles
Authors: K. Patel
Journal: BMJ (2008)

“I’m sorry, Mr Jones, but would you mind coming into the patient advice and liaison office?” says the nice woman in the spectacles. “You see, the doctor’s complained about you,” she adds in a slightly gentler tone. 

“It seems that he’s not happy about what happened yesterday when you told him to eeegghum”—she clears her throat—“off in the middle of the waiting room after he refused to prescribe you sleeping tablets.

“We have a trust policy on this: you have to respond within 14 days. We suggest a …
Light chain editing in kappa-deficient animals: a potential mechanism of B cell tolerance.
Authors: E L Prak, M Trounstine, D Huszar, M Weigert
Journal: The Journal of Experimental Medicine (1994)

The genetic organization of the kappa and lambda light chain loci permits multiple, successive rearrangement attempts at each allele. Multiple rearrangements allow autoreactive B cells to escape clonal deletion by editing their surface receptors. Editing may also facilitate efficient B cell production by salvaging cells with nonproductive light chain (L chain) rearrangements. To study receptor editing of kappa L chains, we have characterized B cells from mice hemizygous for the targeted inactivation of kappa (JCkD/wt) which have an anti-DNA heavy chain transgene, 3H9. Hybridomas from JCkD/wt mice exhibited an increased frequency of rearrangements to downstream Jk segments (such as Jk5) compared with most surveys from normal mice, consistent with receptor editing by sequential kappa locus rearrangements in JCkD/wt. We observed an even higher frequency of rearrangements to Jk5 in 3H9 JCkD/wt animals compared with nontransgenic JCkD/wt, consistent with editing of autoreactive kappa in 3H9 JCkD/wt. We also recovered a large number of 3H9 JCkD/wt lines with Vk12/13-Jk5 rearrangements and could demonstrate by PCR and Southern analysis that up to three quarters of these lines underwent multiple kappa rearrangements. To investigate editing at the lambda locus, we used homozygous kappa-deficient animals (JCkD/JCkD and 3H9 JCkD/JCkD). The frequencies of V lambda 1 and V lambda 2 rearrangements among splenic hybridomas in 3H9 JCkD/JCkD were reduced by 75% whereas V lambda X was increased 5-10-fold, compared with nontransgenic JCkD/JCkD animals. This indicates that V lambda 1 and V lambda 2 are negatively regulated in 3H9 JCkD/JCkD, consistent with earlier studies that showed that the 3H9 heavy chain, in combination with lambda 1 binds DNA. As successive lambda rearrangements to V lambda X do not inactivate V lambda 1, the consequence of lambda editing in 3H9 JCkD/JCkD would be failed allelic exclusion at lambda. However, analysis of 18 3H9 JCkD/JCkD hybridomas with V lambda 1 and V lambda X DNA rearrangements revealed that most of these lines do not have productive lambda 1 rearrangements. In sum, both kappa and lambda loci undergo editing to recover from nonproductive rearrangement, but only kappa locus editing appears to play a substantial role in rescuing autoreactive B cells from deletion.
Antigen targeting to myeloid-specific human Fc gamma RI/CD64 triggers enhanced antibody responses in transgenic mice.
Authors: I A Heijnen, M J van Vugt, N A Fanger, R F Graziano, T P de Wit, F M Hofhuis, P M Guyre, P J Capel, J S Verbeek, J G van de Winkel
Journal: Journal of Clinical Investigation (1996)

Besides their phagocytic effector functions, myeloid cells have an essential role as accessory cells in the induction of optimal humoral immune responses by presenting captured antigens and activating lymphocytes. Antigen presentation by human monocytes was recently found to be enhanced in vitro through the high-affinity Fc receptor for IgG (Fc gamma RI; CD64), which is exclusively present on myeloid cells. To evaluate a comparable role of Fc gamma RI in antigen presentation in vivo, we generated human Fc gamma RI transgenic mice. Under control of its endogenous promoter, human Fc gamma RI was selectively expressed on murine myeloid cells at physiological expression levels. As in humans, expression was properly regulated by the cytokines IFN-gamma, G-CSF, IL-4, and IL-10, and was up-regulated during inflammation. The human receptor expressed by murine macrophages bound monomeric human IgG and mediated particle phagocytosis and IgG complex internalization. To evaluate whether specific targeting of antigens to Fc gamma RI can induce enhanced antibody responses, mice were immunized with an anti-human Fc gamma RI antibody containing antigenic determinants. Transgenic mice produced antigen-specific antibody responses with high IgG1 titers and substantial IgG2a and IgG2b responses. These data demonstrate that human Fc gamma RI on myeloid cells is highly active in mediating enhanced antigen presentation in vivo, and show that anti-Fc gamma RI mAbs are promising vaccine adjuvants.
Understanding sensitivity and specificity with the right side of the brain
Authors: T.-W. Loong
Journal: BMJ (2003)

Can you explain why a test with 95% sensitivity might identify only 1% of affected people in the general population? The visual approach in this article should make the reason clearer 

I first encountered sensitivity and specificity in medical school. That is, I remember my eyes glazing over on being told that “sensitivity = TP/TP+FN, where TP is the number of true positives and FN is the number of false negatives.” As a doctor I continued to encounter sensitivity and specificity, and my bewilderment turned to frustration–these seemed such basic concepts; why were they so hard to grasp? Perhaps the left (logical) side of my brain was not up to the task of comprehending these ideas and needed some help from the right (visual) side. What follows are diagrams that were useful to me in attempting to better visualise sensitivity, specificity, and their cousins positive predictive value and negative predictive value.

I will be using four symbols in these diagrams (fig 1). Let us start by looking at a hypothetical population (fig 2). The size of the population is 100 and the number of people with the disease is 30. The prevalence of the disease is therefore 30/100 = 30%.



Fig 1 
Key to symbols





Fig 2 
Hypothetical population



Now let us imagine applying a diagnostic test for the disease to this population and obtaining the results shown in figure 3. The test has correctly identified most, but not all of the people with the disease. It has also correctly labelled as disease …
Firm foundation for senior house officers: Junior doctors should become progressively more enabled
Authors: Chris M Laing
Journal: BMJ (2004)

Firm foundation for senior house officers Five years is long enoughEditor-The editorial by Gallen and Peile signals anything but a firm foundation for training junior doctors. 1 The first foundation year will essentially be an extension of undergraduate training, its doctors allowed only to observe medical practice.And doctors in foundation year 2 will be "career tourists," spending too little time in each specialty to be able to offer much service in return.Medical educationalists should realise that nurses and other paramedical groups are encroaching on traditional medical practice and do not seem to need the sort of extended training we demand of medical students.For example, a six week course apparently enables paramedics to administer safely almost all drugs used in emergency practice.By contrast we seem intent on postponing the time at which our bright and enthusiastic young doctors can start treating patients.Five years is quite long enough to learn the theory of medicine.After that, the sooner young doctors are allowed to start treating patients, in a supervised setting, the better.
Heart valve records falsified.
Authors: M. Shiu
Journal: BMJ (1992)

Dangers of ozone depletion SIR,-The dangers of ozone depletion in the United Kingdom, particularly with regard to non- melanoma skin cancer, are probably much greater than estimated in the recent article on this topic by Fiona Godlee.'The figures given in the article suggest that non-melanoma skin cancer may rise by 8000 cases a year in Britain if there is a 10% reduction in total column ozone.This figure is based on current incidence figures from cancer registries,-which are widely accepted as being gross underestimates.2I recently suggested that the true incidence of non-melanoma skin cancer in England and Wales may be close to 100 000 cases a year.3If this is true then, using a formula devised at the National Cancer Institute, Bethesda, Maryland,4 we might expect something like 35 000 extra non-melanoma skin cancers each year in England and Wales.Furthermore, there would probably be a relative increase in the potentially more dangerous squamous cell carcinoma compared with basal cell carcinoma.'Of course, these figures should not be taken at their face value as it is difficult to give an exact percentage rise in skin cancers because predicting what changes may occur in holiday and clothing habits is impossible.6The article therefore highlights the inadequacy of registration of skin cancer in the United Kingdom.Few attempts have been made to define the extent of the problem, and thus monitoring adequately any changes that may occur in the incidence of skin cancer is going to be impossible.As I have pointed out previously, there is an urgent need to review and improve registration of skin cancer throughout the United Kingdom.
Cardiac Output in Rats During the Development of Cardiac Hypertrophy
Authors: MARGARET BEZNAK
Journal: Circulation Research (1958)

Cardiac output, reserve force of the heart, total peripheral resistance and weights of the heart and other organs were determined in normal rats, and in rats at different times after their aortas were narrowed just below the diaphragm. Although the output of the hypertrophied heart was normal, its reserve force was greater.
Bronchial and extrabronchial factors in chronic airflow obstruction
Authors: D. G. Leaver, A. E. Tattersfield, N. B. Pride
Journal: Thorax (1974)

<b>Leaver, D. G., Tattersfield, A. E., and Pride, N. B. (1974).</b><i>Thorax</i>, <b>29</b>, 394-400. <b>Bronchial and extrabronchial factors in chronic airflow obstruction.</b> Chronic airflow obstruction may be due either to disease of the airway wall and lumen or to loss of airway-distending forces acting on the outer wall of the bronchus. In 17 patients with chronic airflow obstruction the relative importance of bronchial and extrabronchial factors was assessed by analysing the relation between airways conductance and static transpulmonary pressure over a range of lung volumes. Using previously established clinical, radiological, and functional criteria (which did not include measurements of the mechanical properties of the lungs), six of these patients had evidence of widespread emphysema and six patients had predominant `bronchial9 disease. In four of the six `emphysematous9 patients there was no functional evidence of disease of the bronchial wall or lumen during quiet breathing, and airway narrowing could be explained by loss of airway-distending forces. The six patients with characteristic `bronchial9 features showed functional evidence of disease of the bronchial wall or lumen.
Identification of a P2X7 receptor in GH(4)C(1) rat pituitary cells: a potential target for a bioactive substance produced by Pfiesteria piscicida.
Authors: K L Kimm-Brinson, P D Moeller, M Barbier, H Glasgow, J M Burkholder, J S Ramsdell
Journal: Environmental Health Perspectives (2001)

We examined the pharmacologic activity of a putative toxin (pPfTx) produced by Pfiesteria piscicida by characterizing the signaling pathways that induce the c-fos luciferase construct in GH(4)C(1) rat pituitary cells. Adenosine-5'-triphosphate (ATP) was determined to increase and, at higher concentrations, decrease luciferase activity in GH(4)C(1) rat pituitary cells that stably express c-fos luciferase. The inhibition of luciferase results from cytotoxicity, characteristic of the putative P. piscicida toxin (pPfTx). The actions of both pPfTx and ATP to induce c-fos luciferase were inhibited by the purinogenic receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Further characterization of a P2X receptor on the GH(4)C(1) cell was determined by the analog selectivity of P2X agonists. The P2X1/P2X3 agonist alpha,beta-methylene ATP (alpha,beta-MeATP) failed to increase or decrease c-fos luciferase. However, the P2X7 agonist 2',3'-(4-benzoyl)benzoyl ATP (BzATP), which had a predominant cytotoxic effect, was more potent than ATP. Immunoblot analysis of GH(4)C(1) cell membranes confirmed the presence of a 70-kDa protein that was immunoreactive to an antibody directed against the carboxy-terminal domain unique to the P2X7 receptor. The P2X7 irreversible antagonist oxidized-ATP (oxATP) inhibited the action of ATP, BzATP, and pPfTx. These findings indicate that GH(4)C(1) cells express purinogenic receptors with selectivity consistent with the P2X7 subtype and that this receptor pathway mediates the induction of the c-fos luciferase reporter gene by ATP and the putative Pfiesteria toxin
Abstract 12075: Is Revascularization an Effective Therapy for Heart Failure With Preserved Ejection Fraction?
Authors: Seok-Jae Hwang, Vojtech Melenovsky, Barry A Borlaug
Journal: Circulation (2013)

Background: Myocardial ischemia acutely causes diastolic dysfunction, and coronary artery disease (CAD) is commonly observed in patients with heart failure and preserved ejection fraction (HFpEF). ...
A prospective study of G-CSF–primed bone marrow as a stem-cell source for allogeneic bone marrow transplantation in children: a Pediatric Blood and Marrow Transplant Consortium (PBMTC) study
Authors: Haydar Frangoul, Eneida R. Nemecek, Dean Billheimer, Michael A. Pulsipher, Shakila Khan, Ann Woolfrey, Becky Manes, Catherine Cole, Mark C. Walters, Mouhab Ayas, Yaddanapudi Ravindranath, John E. Levine, Stephan A. Grupp
Journal: Blood (2007)
Combined phlebography and arthrography in patients with painful swollen calf.
Authors: J J Belch, N C McMillan, I Fogelman, H Capell, C D Forbes
Journal: BMJ (1981)

Combined phlebography and arthrography in patients with painful swollen calf Anticoagulant treatment is potentially hazardous' and, since the commonest reason for anticoagulation in hospital is the treatment of deep vein thrombosis, it is of paramount importance that the diagnosis be correctly established.Ruptured Baker's cyst (pseudothrombophlebitis syndrome) is a well-recognised cause of confusion in the diagnosis of deep vein thrombosis.Many workers have emphasised the need for a high index of clinical suspicion combined with either phlebography or arthrography in the differential diagnosis of the two conditions.Results of this study suggest that both phlebography and arthrography are essential for an accurate diagnosis to be reached. CommentTo establish that the patient's infection was laboratory acquired it was necessary to show that the laboratory strain with which she was working was identical with the strain isolated from her urine.
Deviation from additivity in mixture toxicity: relevance of nonlinear dose-response relationships and cell line differences in genotoxicity assays with combinations of chemical mutagens and gamma-radiation.
Authors: Werner K Lutz, Spyros Vamvakas, Annette Kopp-Schneider, Josef Schlatter, Helga Stopper
Journal: Environmental Health Perspectives (2002)

Sublinear dose-response relationships are often seen in toxicity testing, particularly with bioassays for carcinogenicity. This is the result of a superimposition of various effects that modulate and contribute to the process of cancer formation. Examples are saturation of detoxification pathways or DNA repair with increasing dose, or regenerative hyperplasia and indirect DNA damage as a consequence of high-dose cytotoxicity and cell death. The response to a combination treatment can appear to be supra-additive, although it is in fact dose-additive along a sublinear dose-response curve for the single agents. Because environmental exposure of humans is usually in a low-dose range and deviation from linearity is less likely at the low-dose end, combination effects should be tested at the lowest observable effect levels (LOEL) of the components. This principle has been applied to combinations of genotoxic agents in various cellular models. For statistical analysis, all experiments were analyzed for deviation from additivity with an n-factor analysis of variance with an interaction term, n being the number of components tested in combination. Benzo[a]pyrene, benz[a]anthracene, and dibenz[a,c]anthracene were tested at the LOEL, separately and in combination, for the induction of revertants in the Ames test, using Salmonella typhimurium TA100 and rat liver S9 fraction. Combined treatment produced no deviation from additivity. The induction of micronuclei in vitro was investigated with ionizing radiation from a 137Cs source and ethyl methanesulfonate. Mouse lymphoma L5178Y cells revealed a significant 40% supra-additive combination effect in an experiment based on three independent replicates for controls and single and combination treatments. On the other hand, two human lymphoblastoid cell lines (TK6 and WTK1) as well as a pilot study with human primary fibroblasts from fetal lung did not show deviation from additivity. Data derived from one cell line should therefore not be generalized. Regarding the testing of mixtures for deviation from additive toxicity, the suggested experimental protocol is easily followed by toxicologists.