tbuckley/cabot-search huggingface dataset:
Myocardial Uptake and Redistribution of <sup>99m</sup> Tc-N-NOET in Dogs With Either Sustained Coronary Low Flow or Transient Coronary Occlusion
Authors: Gérald Vanzetto, Dennis A. Calnon, Mirta Ruiz, Denny D. Watson, Roberto Pasqualini, George A. Beller, David K. Glover
Journal: Circulation (1997)

Background 99m Tc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes over time. We sought to better define the redistribution kinetics of NOET using open-chest canine models of sustained low coronary flow (protocol 1) and transient coronary occlusion followed by reflow (protocol 2). Methods and Results In protocol 1 (n=10), NOET and 201 Tl were injected during low flow in the left anterior descending coronary artery (LAD) that was sustained for 2 hours. Protocol 2 dogs (n=6) were injected with NOET during 20 minutes of LAD occlusion followed by 2 hours of reflow. In both protocols, serial NOET planar images were acquired, and myocardial flow and 2-hour tracer activities were determined by gamma-well counting. Defect resolution was observed on images in both protocols. Initial defect count ratios, reflecting flow disparity at injection (0.66±0.03 and 0.57±0.04, respectively), increased over 2 hours (0.73±0.02 and 0.75±0.04, respectively; P &lt;.001 versus initial). Quantitative imaging showed that NOET redistribution resulted from greater clearance from normal areas versus low-flow or transiently occluded areas. In protocol 1, 2-hour NOET and 201 Tl stenotic-to-normal tissue activity ratios were similar (0.76±0.06 versus 0.73±0.04, P =NS) and higher than injection flow ratios (0.52±0.06 and 0.56±0.07, respectively, P &lt;.001), consistent with tracer redistribution. In protocol 2, NOET redistributed to an even greater extent (injection flow ratio, 0.27±0.04; 2-hour tissue activity ratio, 0.84±0.03, P &lt;.001). Conclusions NOET is the first 99m Tc-labeled myocardial imaging agent with kinetics similar to 201 Tl in experimental models, permitting redistribution imaging. NOET appears to be a promising agent for assessing patients with coronary artery disease.
TCT-342 Risk and Consequences of Periprocedural Myocardial Infarction Following Off-Label Use of Second Generation Drug-Eluting Stents: Two-Year Follow-up in the TWENTE Trial
Authors: Hanim Sen, Ming Kai Lam, Kenneth Tandjung, Mounir W. Basalus, Martin G. Stoel, Gert van Houwelingen, F. de Man, Hans W. Louwerenburg, Gerard C. Linssen, Mark B. Nienhuis, Marije M. Löwik, Job van der Palen, Clemens von Birgelen
Journal: Journal of the American College of Cardiology (2013)
Arteriographic Assessment of Placental Vascularity after Antepartum Haemorrhage
Authors: J. G. Hill, F. J. Brunton
Journal: BMJ (1968)

During the last decade there has been a gradual shift of emphasis in the management of antepartum haemorrhage.Placenta praevia, dangerous as it may be, presents fewer prob- lems of management since the adoption of conservative therapy and the increased use of caesarean section as advocated by Macafee (1945).Stallworthy (1951) declared that in the man- agement of placenta praevia our aim should be a maternal mortality of nil and a foetal mortality of less than 10%, and these figures have now been achieved in most modem departments.
Clinical Investigations: A New Section for The Journal
Authors: Lawrence D. Grouse
Journal: JAMA (1982)

The publication of laboratory research using animal models is of great importance, but it does not replace patient-based forms of clinical research as the cornerstone of a general medical journal. Yet, many of the most important advances in medical research of the past few decades have depended on laboratory investigations that did not involve human subjects. For practical and ethical reasons, many elegant and conceptually illuminating experiments can be done only with nonhuman models. A journal that ignores this area of research risks becoming irrelevant to a large audience of practitioners and physicians in training who are well versed in basic science concepts and who wish to maintain such an in-depth basis for their practice.  With this issue,The Journalwill begin publishing a new section of fundamental laboratory investigation under the heading CLINICAL INVESTIGATIONS. These articles will typify more experimental and theoretical approaches to medical research than do many
Persistent pain: Trim the branches or fell the tree?
Authors: Richard H. Gracely
Journal: Behavioral and Brain Sciences (1997)

In patients with pain characterized by a painful focus and allodynia, the painful symptoms arise from altered central processing that is initiated and subsequently maintained by persistent input from nociceptive afferents. Treatments directed at this normal consequence of persistent input are inherently limited. The most efficacious treatments will target the pathology, the various sources of ongoing nociceptor input. [blumberg et al.; coderre &amp; katz; dickenson]
Formation of 17-Allylamino-Demethoxygeldanamycin (17-AAG) Hydroquinone by NAD(P)H:Quinone Oxidoreductase 1: Role of 17-AAG Hydroquinone in Heat Shock Protein 90 Inhibition
Authors: Wenchang Guo, Philip Reigan, David Siegel, Joseph Zirrolli, Daniel Gustafson, David Ross
Journal: Cancer Research (2005)

Abstract We have examined the role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the bioreductive metabolism of 17-allylamino-demethoxygeldanamycin (17-AAG). High-performance liquid chromatography (HPLC) analysis of the metabolism of 17-AAG by recombinant human NQO1 revealed the formation of a more polar metabolite 17-AAGH2. The formation of 17-AAGH2 was NQO1 dependent, and its formation could be inhibited by the addition of 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), a mechanism-based (suicide) inhibitor of NQO1. The reduction of 17-AAG to the corresponding hydroquinone 17-AAGH2 was confirmed by tandem liquid chromatography-mass spectrometry. 17-AAGH2 was relatively stable and only slowly underwent autooxidation back to 17-AAG over a period of hours. To examine the role of NQO1 in 17-AAG metabolism in cells, we used an isogenic pair of human breast cancer cell lines differing only in NQO1 levels. MDA468 cells lack NQO1 due to a genetic polymorphism, and MDA468/NQ16 cells are a stably transfected clone that express high levels of NQO1 protein. HPLC analysis of 17-AAG metabolism using cell sonicates and intact cells showed that 17-AAGH2 was formed by MDA468/NQ16 cells, and formation of 17-AAGH2 could be inhibited by ES936. No 17-AAGH2 was detected in sonicates or intact MDA468 cells. Following a 4-hour treatment with 17-AAG, the MDA468/NQ16 cells were 12-fold more sensitive to growth inhibition compared with MDA468 cells. More importantly, the increased sensitivity of MDA468/NQ16 cells to 17-AAG could be abolished if the cells were pretreated with ES936. Cellular markers of heat shock protein (Hsp) 90 inhibition, Hsp70 induction, and Raf-1 degradation were measured by immunoblot analysis. Marked Hsp70 induction and Raf-1 degradation was observed in MDA468/NQ16 cells but not in MDA468 cells. Similarly, downstream Raf-1 signaling molecules mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase and ERK also showed decreased levels of phosphorylation in MDA468/NQ16 cells but not in MDA468 cells. The ability of 17-AAG and 17-AAGH2 to inhibit purified yeast and human Hsp90 ATPase activity was examined. Maximal 17-AAG–induced ATPase inhibition was observed in the presence of NQO1 and could be abrogated by ES936, showing that 17-AAGH2 was a more potent Hsp90 inhibitor compared with 17-AAG. Molecular modeling studies also showed that due to increased hydrogen bonding between the hydroquinone and the Hsp90 protein, 17-AAGH2 was bound more tightly to the ATP-binding site in both yeast and human Hsp90 models. In conclusion, these studies have shown that reduction of 17-AAG by NQO1 generates 17-AAGH2, a relatively stable hydroquinone that exhibits superior Hsp90 inhibition.
Gwyn Meirion Mason
Authors: R W Galloway
Journal: BMJ (2006)

​FormerFormer general practitioner and civilian medical officer to H M Forces (b 1925; q Liverpool 1953; MRCGP), died from cardiac and respiratory disease on 21 January 2006.



Figure 1



After war service in the Royal Navy, Gwyn entered general practice in Cheshire, Birmingham, and Somerset, where he was also a busy police surgeon. He became a civilian medical officer in the Bristol/Wiltshire area in 1979 until retirement. He leaves a wife and three children.
Amelioration of diabetic nephropathy by treatment with monoclonal antibodies against glycated albumin
Authors: Margo P. Cohen, Elizabeth Hud, Van-Yu Wu
Journal: Kidney International (1994)

The pathogenesis of diabetic nephropathy is incompletely understood, but increased nonenzymatic glycation of proteins is considered an important contributory factor. Glycated albumin, which is increased in diabetic sera and is preferentially transported into the renal glomerulus, induces an increase in Type IV collagen production and a decrease in proliferative capacity by mesangial cells in culture. These effects resemble the abnormalities that characterize the glomerular mesangium in diabetes and are prevented by monoclonal antibodies that specifically react with Amadori adducts in glycated albumin. To explore the possibility that the in vitro effects of glycated albumin on mesangial cell biology pertain to the in vivo situation, we examined the effect of treatment with the A717 monoclonal antibodies on glomerular functional and structural changes in a rodent model of genetic diabetes, the db/db mouse. Weekly parenteral antibody administration reduced the elevated albumin excretion and attenuated the mesangial expansion that were observed in the untreated db/db mice that served as controls. Monoclonal antibody treatment also was shown to lower plasma concentrations of glycated albumin in diabetic mice. Thus, reducing glycated albumin concentrations and/or blocking its biologically active epitopes has a salutary influence on the pathogenesis of diabetic nephropathy. The findings indicate that glycated albumin participates in the development of the glomerular lesion in the db/db mouse, and suggest a new approach to the therapy of this complication of diabetes.
Quantitative analysis of T-lymphocyte subsets in atopic eczema, using monoclonal antibodies and flow cytoafluorimetry
Authors: C.B. ZACHARY, D.M. MACDONALD
Journal: British Journal of Dermatology (1983)

An analysis of T-lymphocyte subpopulations was performed on thirty-eight consecutive patients with atopic eczema, using monoclonal antibodies and flow cytofluorimetry. The total T-lymphocyte and helper T-cell numbers did not differ significantly from those of a matched control group, but there was a highly significant reduction in suppressor T-cell numbers among the atopic group. Both suppressor T-cell deficiency and circulating IgE elevation were found to correlate positively with disease activity. Food specific IgE levels to milk and egg were ascertained by radioallergosorbent (RAST) studies. These proved positive in seven out of thirty-five atopics (20%).
Survival of patients with cystic fibrosis
Authors: E J Simmonds, J M Littlewood
Journal: BMJ (1989)

cardiorespiratory arrest (the cause for which was not established).During her resuscitation she was dragged across a floor and received severe full thickness lacerations to the purpuric and atrophic areas of skin on both arms and both legs.The skin loss on her right leg required grafting.She was discharged seven weeks after admission.Subsequently she had pain and discomfort in areas of scar tissue.She required beclomethasone 1-1 5 mg daily for her asthma.While she was stabilised on a dose of 1 mg beclomethasone daily a short tetracosactrin test showed borderline impairment of her adrenal function (basal plasma cortisol concentration 150 nmol/l, 30 minutes after tetracosactrin 0-25 mg intramuscularly 531 nmoL/l).Although senile purpura and corticosteroid purpura resemble each other closely,4 this patient's age, the location of bruising on her legs4 and the appearance of the bruising some months after taking higher doses of inhaled beclomethasone suggest that her purpura was induced by the steroid.Doctors should continue to be aware of the possibility of appreciable systemic side effects of this form of treatment.
Respiratory depression after alfentanil infusion
Authors: H A Waldron, R F Cookson
Journal: BMJ (1985)

common in the younger patients and that the distribution of the various virus infections corresponded to expectations with respect to age.Our range of testing was limited, and many common virus infections-for instance, ECHO virus, parainfluenza virus, and so on-would have gone undetected.Our incidence of 30 4% is, therefore, almost certainly an underestimate.Both the incidence and the density of S aureus carriage in the nasopharynx increase dramatically during viral upper respiratory tract infections.4We believe that this, taken with the temporary suppression of host defence mechanisms during acute virus infections,3 may explain many cases of S aureus septicaemia and endocarditis of apparently spontaneous onset.Confirmation of these findings would suggest vaccination, where feasible, against common virus infections for patients with valvular heart disease, especially when young or after heart surgery.
The Major Allergens of Birch Pollen and Cow Milk, Bet v 1 and Bos d 5, Are Structurally Related to Human Lipocalin 2, Enabling Them to Manipulate T-Helper Cells Depending on Their Load with Siderophore-Bound Iron
Authors: Erika Jensen-Jarolim, Cristina Gomez-Casado, Luis F.F. Pacios, Gerlinde Hofstetter, Nadine Mothes-Luksch, Georg A. Roth, Josef Singer, Araceli Diaz-Perales, Franziska Roth-Walter
Journal: Journal of Allergy and Clinical Immunology (2015)
Clinical and statistical validity of conventional prognostic factors in predicting short-term survival among cirrhotics
Authors: Claire Infante-Rivard, Santiago Esnaola, Jean-Pierre Villeneuve
Journal: Hepatology (1987)

The objective of this study was to assess the prognostic validity of Child-Turcotte classification with regard to short-term (1-year) survival. The Child-Turcotte classification, as modified by Pugh et al., was recorded on admission in 177 cirrhotic patients. The variables that comprise the Pugh modification are ascites, encephalopathy, serum albumin, serum bilirubin and prothrombin time. Using multiple logistic regression, we evaluated the contribution of different models to the likelihood of survival, defining different ways to use the Pugh score. The Pugh score categorized in three strata (5 to 6, 7 to 9 and 10 to 15) captured less variance in the survival than the Pugh score counted from 5 to 15. This, in turn, captured less variance than a model in which the parameters of the Pugh score were analyzed according to their original units. The prediction rule based on the last model was tested in another sample of cirrhotics. The “original unit” model was studied in both training and testing samples, using receiver-operating characteristic curves to evaluate its clinical validity (sensitivity and specificity). The prediction rule based on the “original units” Pugh score allowed for a good discrimination of patients who lived and those who died. (At the point of maximum discrimination, sensitivity and specificity reached a mean of 80%.) Validity of the prediction rule was confirmed by the testing sample. The qualities of simplicity, availability, low cost and good discriminating power for a life or death outcome make the Pugh score a very useful method to estimate prognosis in patients with cirrhosis.
Christmas Books: A confusion of charts
Authors: M. Jamieson
Journal: BMJ (1980)

words, serenity, fruitfulness, originality, and life itself can grow and flourish only within the framework of society.Less important, but of interest and some relevance to rehabilitation, is the attempt to measure scientifically the degree to which Helen's other senses had developed.Blind and deaf she remained, but what of smell and touch?Helen was sure that she was much above average, but the tests said these senses were only normally developed, not more.One does not repudiate the scientists' findings, but the mind cries out that the test had missed some vital component.What of interpreta- tion, the power to imagine, conjure up, understand, through these senses ?It is nigh impossible to doubt that she used these senses better than you or I.
John Harry Howard Glyn
Authors: K W Symons
Journal: BMJ (2006)

​FormerFormer consultant rheumatologist London (b London 1921; q Cambridge 1944; MA, MD, FRCP), d 1 October 2005.



Figure 1



John served in the Royal Air Force from 1947 to 1949. He was awarded a Fulbright scholarship at New York University in 1952. In 1959 he was appointed senior registrar in rheumatology at The London Hospital. John was a member of Dr W S C Copeman's team carrying out pioneering research into the use of steroids in rheumatoid arthritis, and he wrote his MD thesis on this. He was appointed consultant rheumatologist at the Prince of Wales Hospital, Tottenham, in 1970 and later became consultant rheumatologist at the St Charles and St Mary's Rehabilitation Centre. He leaves a wife, Daphne; two children; and six grandchildren.
Safety, Resource Use, and Quality of Life in Paramount: A Phase III Study of Maintenance Pemetrexed Versus Placebo after Induction Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer
Authors: Cesare Gridelli, Filippo de Marinis, Jean-Louis Pujol, Martin Reck, Rodryg Ramlau, Barbara Parente, Thierry Pieters, Gary Middleton, Jesus Corral, Katherine Winfree, Symantha Melemed, Anna Zimmermann, William John, Julie Beyrer, Nadia Chouaki, Carla Visseren-Grul, Luis G. Paz-Ares
Journal: Journal of Thoracic Oncology (2012)
PMO-150 Second harmonic generation microscopy of collagen and evaluation of liver fibrosis in chronic hepatitis C (CHC) infection: Abstract PMO-150 Figure 1
Authors: G E Dolman, D Sevrain, C Odin, Y Le Grand, A M Zaitoun, W L Irving, I N Guha
Journal: Gut (2012)

<h3>Introduction</h3> There is an urgent need to create tools to quantify collagen in liver fibrosis to facilitate stratification of disease and development of anti-fibrotic agents. Multiphoton microscopy enables imaging of unstained biopsies using endogenous sources of non-linear signals such as Two-Photon Excitation Fluorescence (TPEF) and Second Harmonic Generation (SHG). SHG allows specific detection of non-centrosymmetric structures such as fibrillar collagen, mainly type I. The SHG score is a measure of relative collagen area and is obtained by post-acquisition SHG/TPEF image processing. We have assessed the ability of our method to quantify collagen in advanced fibrosis due to CHC, with respect to Ishak stage (IS). <h3>Methods</h3> Biopsies from patients with advanced fibrosis (IS ≥3) were selected from 1 centre in the Trent Study of Patients with Hepatitis C Virus, a prospective cohort study formed in 1991. Index biopsies prior to 2008 were selected and notes reviewed for subsequent liver related outcomes (LRO). LRO was defined as variceal bleed, ascites, encephalopathy, HCC or liver related death. SHG was measured on 4μm FFPE sections. A mask of the biopsy area was created with TPEF. Image processing was performed by two independent researchers, blinded to Ishak stage, using in-house macros and each using different software (Image J &amp; Matlab). PASW 17.0 was used for statistical analysis. <h3>Results</h3> The SHG score was acquired in 58 of 83 biopsies (66%). 25 were excluded due to signal artefact from paraffin, obscuring SHG signal from collagen. There was no significant difference in scoring by two researchers (p&lt;0.001). The median SHG score was 15.96% (IQR 11.3–21.3%). Abstract PMO-150 figure 1 shows the median SHG score for each IS. SHG signal increased with disease severity (IS3:10.1%; IS4:14.1%; IS5:14.1%; IS6:21.2%). LRO occurred in 15 patients after a median of 57 months post-biopsy. The mean SHG score at index biopsy was 19.1% in those with, and 16.6% in those without subsequent LRO (non-significant difference, p&gt;0.05). <h3>Conclusion</h3> SHG has proved to be a valuable method of quantifying collagen in liver fibrosis and does not require standard histochemical stains. Further development of this quantitative measure may result in a tool to assess response to anti-fibrotic therapy and progression to clinical endpoints. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Gailhouste L</b>, <i>et al.</i> Fibrillar collagen scoring by second harmonic microscopy: A new tool in the assessment of liver fibrosis. <i>J Hep</i> 2010;<b>52</b>:398–406. 2. <b>Guilbert T</b>, <i>et al.</i> A robust collagen scoring method for human liver fibrosis by second harmonic microscopy. <i>Opt Expr</i> 2010;<b>18</b>:25794–807.
The future of SIMS: Who embodies which smile and when?
Authors: Paula M. Niedenthal, Martial Mermillod, Marcus Maringer, Ursula Hess
Journal: Behavioral and Brain Sciences (2010)

Abstract The set of 30 stimulating commentaries on our target article helps to define the areas of our initial position that should be reiterated or else made clearer and, more importantly, the ways in which moderators of and extensions to the SIMS can be imagined. In our response, we divide the areas of discussion into (1) a clarification of our meaning of “functional,” (2) a consideration of our proposed categories of smiles, (3) a reminder about the role of top-down processes in the interpretation of smile meaning in SIMS, (4) an evaluation of the role of eye contact in the interpretation of facial expression of emotion, and (5) an assessment of the possible moderators of the core SIMS model. We end with an appreciation of the proposed extensions to the model, and note that the future of research on the problem of the smile appears to us to be assured.
The Two Cultures and the Scientific Revolution
Authors: Robert S. Karsh
Journal: JAMA (1961)

Last year's Rede Lecture at Cambridge by C. P. Snow is now available in a slim, thoughtful, and disturbing volume entitled<i>The Two Cultures and the Scientific Revolution</i>. It runs a mere 58 pages of direct, insistent prose and can be read in one hour. Since it takes so little time to courageously tackle two problems vital to scientists, this unimposing book may well be the greatest literary bargain of an inflated publishing age. The "two cultures" in the title are the modern culture of the scientific intellectual and the traditional culture of the literary intellectual. With a foot in each cultural camp, C. P. Snow comes uniquely armed to the fray. He states his own qualifications: "By training I was a scientist; by vocation I was a writer." When such an awesomely equipped spokesman says, "I believe the intellectual life of the whole of western society is increasingly being