tbuckley/cabot-search huggingface dataset:
The Clinical Thermopile
Authors: T. C. Allbutt
Journal: BMJ (1875)

THE BRITIS_ MEDICAL A7OURNAL.309 results of mercury, the evidence seems opposed to the belief that the lenticular opacity is also due to the influence of the drug.The great frequency of mercurial teeth without lainellar cataract, and the not very infrequent occurrence of lamellar cataract without mercurial teeth, are opposed to this view.8.That the very frequent coincident occurrence of lamliellar cataract with defective teeth, is to be explained by reference to the frequency with which mercury is given for the treatment of convulsions in in- fancy.9. That there is no reason whatever for supposing that lamellar cataracts have any connection with hereditary syphilis.IO.That, whilst it is certainly true that lamellar cataracts are com- monly mdt with in young persons who show general defects of development, short stature, ill-shaped heads, defective intellect, dwarfed lower jaws, or other physiognomical peculiarities, yet there is seldom any proof of the existence of rickets; whilst it is quite possible that the peculiarities mentioned may be due to the disturbance of the nervous system in infancy in connection with the convulsions.II.It is very important to distinguish between mercurial teeth and syphilitic teeth, and the peculiarities presented by each usually render this easy; the two are, however, as might have been expected, not uncommonly met with together.
Women have had "harrowing" experiences over PIP implants scandal
Authors: A. O'Dowd
Journal: BMJ (2012)

Some women have undergone a “harrowing” experience in trying to deal with the impact of the scandal over breast implants made by discredited French manufacturer Poly Implant Prosthese (PIP).

First hand accounts of the experience of almost 200 affected women in the United Kingdom have been submitted to a web forum set up by the parliamentary health select committee, which published a summary of these comments in a report published on 2 July.1

A scandal emerged last year over now bankrupt manufacturer PIP, which used non-medical grade silicone in breast implants that were given to around 47 000 women in the UK.2 3

In March, the health select committee published a …
ESC Working Group Cellular Biology of the Heart: Position Paper: improving the preclinical assessment of novel cardioprotective therapies
Authors: S. Lecour, H. E. Botker, G. Condorelli, S. M. Davidson, D. Garcia-Dorado, F. B. Engel, P. Ferdinandy, G. Heusch, R. Madonna, M. Ovize, M. Ruiz-Meana, R. Schulz, J. P. G. Sluijter, L. W. Van Laake, D. M. Yellon, D. J. Hausenloy
Journal: Cardiovascular Research (2014)

Ischaemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischaemia–reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designed preclinical experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the preclinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes.
Identification of a B cell signature associated with renal transplant tolerance in humans
Authors: Kenneth A. Newell, Adam Asare, Allan D. Kirk, Trang D. Gisler, Kasia Bourcier, Manikkam Suthanthiran, William J. Burlingham, William H. Marks, Ignacio Sanz, Robert I. Lechler, Maria P. Hernandez-Fuentes, Laurence A. Turka, Vicki L. Seyfert-Margolis
Journal: Journal of Clinical Investigation (2010)

Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients.
Randomized Multicenter Investigation of Folate Plus Vitamin B<sub>12</sub>Supplementation in Schizophrenia
Authors: Joshua L. Roffman, J. Steven Lamberti, Eric Achtyes, Eric A. Macklin, Gail C. Galendez, Lisa H. Raeke, Noah J. Silverstein, Jordan W. Smoller, Michele Hill, Donald C. Goff
Journal: JAMA Psychiatry (2013)

More effective treatments are needed for negative symptoms of schizophrenia, which are typically chronic, disabling, and costly. Negative symptoms have previously been associated with reduced blood folate levels, especially among patients with low-functioning variants in genes that regulate folate metabolism, suggesting the potential utility of folate supplementation.To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response.Parallel-group, randomized, double-blind, placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B12.Three community mental health centers affiliated with academic medical centers in the United States.Outpatients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment. Eligible patients were 18 to 68 years old, were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more, and scored 60 or more on the Positive and Negative Syndrome Scale.One hundred forty subjects were randomized to receive daily oral folic acid plus vitamin B12 or placebo.Change in negative symptoms (Scale for the Assessment of Negative Symptoms [SANS]), as well as positive and total symptoms (Positive and Negative Syndrome Scale).Folate plus vitamin B12 improved negative symptoms significantly compared with placebo (group difference, -0.33 change in SANS score per week; 95% CI, -0.62 to -0.05) when genotype was taken into account but not when genotype was excluded. An interaction of the 484C>T variant of FOLH1 (rs202676) with treatment was observed (P = .02), where only patients homozygous for the 484T allele demonstrated significantly greater benefit with active treatment (-0.59 change in SANS score per week; 95% CI, -0.99 to -0.18). In parallel, we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load (P = .03), which persisted until 8 weeks of treatment. Change in positive and total symptoms did not differ between treatment groups.Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia, but treatment response is influenced by genetic variation in folate absorption. These findings support a personalized medicine approach for the treatment of negative symptoms.clinicaltrials.gov Identifier: NCT00611806.
Does This Patient Have an Exudative Pleural Effusion?
Authors: M. Elizabeth Wilcox, Christopher A. K. Y. Chong, Matthew B. Stanbrook, Andrea C. Tricco, Camilla Wong, Sharon E. Straus
Journal: JAMA (2014)

Thoracentesis is performed to identify the cause of a pleural effusion. Although generally safe, thoracentesis may be complicated by transient hypoxemia, bleeding, patient discomfort, reexpansion pulmonary edema, and pneumothorax.To identify the best means for differentiating between transudative and exudative effusions and also to identify thoracentesis techniques for minimizing the risk of complications by performing a systematic review the evidence.We searched The Cochrane Library, MEDLINE, and Embase from inception to February 2014 to identify relevant studies.We included randomized and observational studies of adult patients undergoing thoracentesis that examined diagnostic tests for differentiating exudates from transudates and evaluated thoracentesis techniques associated with a successful procedure with minimal complications.Two investigators independently appraised study quality and extracted data from studies of laboratory diagnosis of pleural effusion for calculation of likelihood ratios (LRs; n = 48 studies) and factors affecting adverse event rates (n = 37 studies).The diagnosis of an exudate was most accurate if cholesterol in the pleural fluid was greater than 55 mg/dL (LR range, 7.1-250), lactate dehydrogenase (LDH) was greater than 200 U/L (LR, 18; 95% CI, 6.8-46), or the ratio of pleural fluid cholesterol to serum cholesterol was greater than 0.3 (LR, 14; 95% CI, 5.5-38). A diagnosis of exudate was less likely when all Light's criteria (a ratio of pleural fluid protein to serum protein >0.5, a ratio of pleural fluid LDH to serum LDH >0.6, or pleural fluid LDH >two-thirds the upper limit of normal for serum LDH) were absent (LR, 0.04; 95% CI, 0.02-0.11). The most common complication of thoracentesis was pneumothorax, which occurred in 6.0% of cases (95% CI, 4.0%-7.0%). Chest tube placement was required in 2.0% of procedures (95% CI, 0.99%-2.9%) in which a patient was determined to have radiographic evidence of a pneumothorax. With ultrasound, a radiologist's marking the needle insertion site was not associated with decreased pneumothorax events (skin marking vs no skin marking odds ratio [OR], 0.37; 95% CI, 0.08-1.7). Use of ultrasound by any experienced practitioner also was not associated with decreased pneumothorax events (OR, 0.55; 95% CI, 0.06-5.3).Light's criteria, cholesterol and pleural fluid LDH levels, and the pleural fluid cholesterol-to-serum ratio are the most accurate diagnostic indicators for pleural exudates. Ultrasound skin marking by a radiologist or ultrasound-guided thoracentesis were not associated with a decrease in pneumothorax events.
Simplified cell culture method for the diagnosis of atypical primary ciliary dyskinesia
Authors: M Pifferi, F Montemurro, A M Cangiotti, V Ragazzo, M Di Cicco, B Vinci, G Vozzi, P Macchia, A L Boner
Journal: Thorax (2009)

The diagnosis of primary ciliary dyskinesia (PCD) can be challenging, and it may be particularly difficult to distinguish primary ciliary disease from the secondary changes after infections.The purpose of the study was to evaluate if nasal epithelial cells, obtained with nasal brushing instead of a biopsy, could be used in a culture system for the diagnosis of PCD in difficult cases.Ciliary motion analysis (CMA) and transmission electron microscopy (TEM) were performed on 59 subjects with persistent or recurrent pneumonia. These investigations allowed the diagnosis of PCD in 13 (22%) patients while the defect of the cilia was considered secondary to infections in 37 (63%) subjects. In the remaining nine (15%) patients the diagnostic evaluation with CMA and TEM remained inconclusive. Ciliogenesis in culture allowed the diagnosis of PCD in four of these patients, it was indicative of a secondary defect in two subjects, and it was not helpful in the remaining three patients.Culture of cells obtained with brushing of the nasal turbinate is not a perfect test, nevertheless it may offer diagnostic help in doubtful cases of PCD.
MYC Phosphorylation, Activation, and Tumorigenic Potential in Hepatocellular Carcinoma Are Regulated by HMG-CoA Reductase
Authors: Zhongwei Cao, Hua Fan-Minogue, David I. Bellovin, Aleksey Yevtodiyenko, Julia Arzeno, Qiwei Yang, Sanjiv Sam Gambhir, Dean W. Felsher
Journal: Cancer Research (2011)

MYC is a potential target for many cancers but is not amenable to existing pharmacologic approaches. Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) by statins has shown potential efficacy against a number of cancers. Here, we show that inhibition of HMG-CoA reductase by atorvastatin (AT) blocks both MYC phosphorylation and activation, suppressing tumor initiation and growth in vivo in a transgenic model of MYC-induced hepatocellular carcinoma (HCC) as well as in human HCC-derived cell lines. To confirm specificity, we show that the antitumor effects of AT are blocked by cotreatment with the HMG-CoA reductase product mevalonate. Moreover, by using a novel molecular imaging sensor, we confirm that inhibition of HMG-CoA reductase blocks MYC phosphorylation in vivo. Importantly, the introduction of phosphorylation mutants of MYC at Ser62 or Thr58 into tumors blocks their sensitivity to inhibition of HMG-CoA reductase. Finally, we show that inhibition of HMG-CoA reductase suppresses MYC phosphorylation through Rac GTPase. Therefore, HMG-CoA reductase is a critical regulator of MYC phosphorylation, activation, and tumorigenic properties. The inhibition of HMG-CoA reductase may be a useful target for the treatment of MYC-associated HCC as well as other tumors.
Exhaled breath temperature in adult cystic fibrosis
Authors: Gabriel Garcia, Noemi Granero, Berta Hendriksen, Deleo Carlos, Baran Ezequiel, Miguel Bergna
Journal: European Respiratory Journal (2011)

Cystic fibrosis (CF) is characterized by chronic airway infection and inflammation, which accounts for most morbidity and deaths. It has been suggested that inflamed airways may increase the exhaled breath temperature (EBT), however, patient with Cystic Fibrosis (CF) may have of the opposite effects. The aim of this study was to measure exhaled breath temperature in adults CF patients by comparison with healthy controls. Fifteen adults CF patients examined (8 female, mean age 28±7 years, VEF1% 44±21%) and 15 healthy persons (7 female, mean age 34±3 years) were recruited for the control group. The measurements of exhaled breath temperature (EBT) were performed with a second generation hand-held device (X-Halo, Delmedical Investments LTD Singapore) using an antibacterial filter (Clear Advantage, Creative Biomedics, Inc).

Mean value of EBT in controls was 33.80±0.87°C and EBT mean value in adults CF patients was 33.53±0.73°C, the difference was not significant (p>0.05). We conclude that patients with CF had EBT similarly to healthy people, contrary to the asthmatics patients, possible due to chronic epithelial cell damage, increased mucosal barrier and the reduce of the vascularity.
Thrombospondin-1 Induction in the Diabetic Myocardium Stabilizes the Cardiac Matrix in Addition to Promoting Vascular Rarefaction Through Angiopoietin-2 Upregulation
Authors: Carlos Gonzalez-Quesada, Michele Cavalera, Anna Biernacka, Ping Kong, Dong-Wook Lee, Amit Saxena, Olga Frunza, Marcin Dobaczewski, Arti Shinde, Nikolaos G. Frangogiannis
Journal: Circulation Research (2013)

Diabetes mellitus is associated with cardiac fibrosis. Matricellular proteins are induced in fibrotic conditions and modulate fibrogenic and angiogenic responses by regulating growth factor signaling.Our aim was to test the hypothesis that the prototypical matricellular protein thrombospondin (TSP)-1, a potent angiostatic molecule and crucial activator of transforming growth factor-β, may play a key role in remodeling of the diabetic heart.Obese diabetic db/db mice exhibited marked myocardial TSP-1 upregulation in the interstitial and perivascular space. To study the role of TSP-1 in remodeling of the diabetic heart, we generated and characterized db/db TSP-1(-/-) (dbTSP) mice. TSP-1 disruption did not significantly affect weight gain and metabolic function in db/db animals. When compared with db/db animals, dbTSP mice had increased left ventricular dilation associated with mild nonprogressive systolic dysfunction. Chamber dilation in dbTSP mice was associated with decreased myocardial collagen content and accentuated matrix metalloproteinase-2 and -9 activity. TSP-1 disruption did not affect inflammatory gene expression and activation of transforming growth factor-β/small mothers against decapendaplegic signaling in the db/db myocardium. In cardiac fibroblasts populating collagen pads, TSP-1 incorporation into the matrix did not activate transforming growth factor-β responses, but inhibited leptin-induced matrix metalloproteinase-2 activation. TSP-1 disruption abrogated age-associated capillary rarefaction in db/db mice, attenuating myocardial upregulation of angiopoietin-2, a mediator that induces vascular regression. In vitro, TSP-1 stimulation increased macrophage, but not endothelial cell, angiopoietin-2 synthesis.TSP-1 upregulation in the diabetic heart prevents chamber dilation by exerting matrix-preserving actions on cardiac fibroblasts and mediates capillary rarefaction through effects that may involve angiopoietin-2 upregulation.
P154 Outpatient Management of Pulmonary Embolism-Patient characteristics and Outcomes: Abstract P154 Table 1.
Authors: A Lakhanpal, C Watters, C Hughes, S Iyer, M Babores
Journal: Thorax (2013)

<h3>Introduction</h3> Management of Pulmonary Embolism (PE) has been until recently largely in-patient based and markedly affects length of stay in these patients. Recent evidence suggests that suspected or confirmed cases of PE can be managed out of hospital<sup>1, 2</sup>. We present our experience of outpatient management of PE in a small district general hospital. <h3>Method</h3> We identified 35 patients investigated/treated for PE as outpatient between March 2012 and June 2013. Demographic and clinical data was collected from case notes. Statistical analysis was performed on Medcalc based on normality. <h3>Result</h3> The table below profiles our cohort. (Table) There was a high PE diagnosis (51%) within our cohort despite most patients being in a low PESI class. Clinical decision made in high PESI class to manage as outpatient. PE was diagnosed in 4 of the 5(80%) patients with a raised Troponin level (odds ratio 1.66, statistically not significant). Out of 21 GP referrals, 13(61.9%) had a positive scan as opposed to 5 of the 13 (38.4%)patients referred from hospital, however this did not attain statistical significance (odds ratio 3.25, p = 0.12). The equivocal CTPA was deemed not PE on clinical grounds. All patients were reviewed by a Registrar or Consultant prior to discharge. No mortality recorded till date. One patient re-presented with exacerbation of Asthma. <h3>Discussion</h3> Carefully selected patients with suspected or confirmed PE can be managed out of hospital. Based on time to imaging, atleast 28 unnecessary inpatient days were avoided leading to £9800 saved and a high pick up rate. In our experience, mortality and re-admission rates have been minimal highlighting outpatient management as a safe and cost-effective strategy in management of PE. <h3>References</h3> Safety of outpatient treatment in acute pulmonary embolism. Erkens PM, Gandara E, Wells P, <i>et al</i>. <i>J Thromb Haemost</i>, Nov 2010, vol/is. 8/11(2412–7), 1538–7836 Outpatient Management of suspected Pulmonary Embolism at a District General Hospital; A Two Month Review. JA Benjamin, A Griffiths, S power, <i>et al</i>. <i>Thorax</i> 2012;<b>67</b>:A123 doi:10.1136/thoraxjnl-2013-204457.305
Phenotypic plasticity and targeting of <scp>S</scp>iglec‐<scp>F</scp><sup>high</sup><scp>CD</scp>11c<sup>low</sup> eosinophils to the airway in a murine model of asthma
Authors: H. Abdala Valencia, L. F. Loffredo, A. V. Misharin, S. Berdnikovs
Journal: Allergy (2015)

Eosinophil recruitment in asthma is a multistep process, involving both trans-endothelial migration to the lung interstitium and trans-epithelial migration into the airways. While the trans-endothelial step is well studied, trans-epithelial recruitment is less understood. To contrast eosinophil recruitment between these two compartments, we employed a murine kinetics model of asthma. Eosinophils were phenotyped by multicolor flow cytometry in digested lung tissue and bronchoalveolar lavage (BAL) simultaneously, 6 h after each ovalbumin (OVA) challenge. There was an early expansion of tissue eosinophils after OVA challenge followed by eosinophil buildup in both compartments and a shift in phenotype over the course of the asthma model. Gradual transition from a Siglec-F(med) CD11c(-) to a Siglec-F(high) CD11c(low) phenotype in lung tissue was associated with eosinophil recruitment to the airways, as all BAL eosinophils were of the latter phenotype. Secondary microarray analysis of tissue-activated eosinophils demonstrated upregulation of specific integrin and chemokine receptor signature suggesting interaction with the mucosa. Using adhesion assays, we demonstrated that integrin CD11c mediated adhesion of eosinophils to fibrinogen, a significant component of epithelial barrier repair and remodeling. To the best of our knowledge, this is the only report to date dissecting compartmentalization of eosinophil recruitment as it unfolds during allergic inflammation. By capturing the kinetics of eosinophil phenotypic change in both tissue and BAL using flow cytometry and sorting, we were able to demonstrate a previously undocumented association between phenotypic shift of tissue-recruited eosinophils and their trans-epithelial movement, which implicates the existence of a specific mechanism targeting these cells to mucosal airways.
Echocardiographic determination of left atrial volumes in children with congenital heart disease.
Authors: S M Yabek, J Isabel-Jones, D R Bhatt, M Nakazawa, R A Marks, J M Jarmakani
Journal: Circulation (1976)

The feasibility of determining left atrial volumes (LAV) from LA echo dimensions was assessed in 36 children (group I) with normal cineangiographically determined LAV and 16 children (group II) with LAV overload. Conventional LA echo dimensions, obtained within 24 hours of cardiac catheterization, were compared to the angiographic LA anterior-posterior minor axes (LAmA) and LAV. There was excellent correlation betweeh the LA echo dimensions and the LAmA. In all patients, the LA echo less than LAmA, the differences being more pronounced in group II. Good correlations were found between the LAV and the LA echo, and were expressed by the equations LAV = 7.5 LA echo1.8 (r = .85) and LAV = 8.1 LA echo2.1 (r = .86) for groups I and II, respectively. Changes in LA configuration with volume overload were shown to cause a disproportionate increase in LAmA compared to the other LA dimensions and the LA echo dimension, thus necessitating the separate regression equations. Echo LA to aortic ratios were 0.86 +/- 0.11 and 1.21 +/- 0.23 (mean +/- SD) for groups I and II, respectively. This method of estimating LAV can be useful in the management of left-to-right intracardiac shunts and mitral regurgitation in infants and children.