tbuckley/cabot-search huggingface dataset:
Surgeons' knowledge base needs to be increased
Authors: R. Madhok, J. Stothard
Journal: BMJ (1996)

though screening is demonstrably cost effective.4Foremost among the unresolved questions is the ability of physicians to treat bone disease once it is detected.The number ofknowledgeable physicians is increasing, but not enough for them to manage the 100-fold increase in caseload that could result from population screening.Today less than 5% of patients with fracture undergo densitometry, and less than one third of the potential patients with indications (for example, those taking corticosteroids or with malabsorption or hyperparathyroidism) are symptomatic.Barlow and col- leagues note that critics confuse clinical densitometry in patients showing symptoms or indications with screening.'Physicians must become educated about bone disease so that they can manage effectively the increased caseload that will result from justified use of densitometry, and they must not be misled by disingenuous arguments against screening.
The Natural History of Rheumatic Fever and Rheumatic Heart Disease
Journal: Circulation (1965)

1. A study has been made 10 years after the end of treatment of the 497 children who were admitted to the U.K./U.S. cooperative clinical trial of the relative merits of ACTH, cortisone, and aspirin in the treatment of acute rheumatic fever. 2. Three hundred and ninety-seven of the cases (79.9 per cent) were known to be alive at 10 years and the status of the heart was known for 347 of them. In addition, 23 (4.6 per cent) had died, 19 from rheumatic fever and rheumatic heart disease, and 77 (15.5 per cent) were untraced. The very low fatality rate is striking. 3. At the end of 10 years, there is no evidence that, on the treatment schedule used in this study, the prognosis has been influenced more by one treatment than another. This confirms the findings reported at 1 year and at 5 years. 4. The most important factor in determining the prevalance of rheumatic heart disease at the end of 10 years is the status of the heart at the time treatment was begun. For cases initially without carditis the prognosis was excellent, since in 94 per cent there was no residual heart disease. In cases initially with carditis but without pre-existing heart disease, the proportion without residual heart disease was 70 per cent for those with only a grade I apical systolic murmur, and 74 per cent for those with only a grade II or III apical systolic murmur. The proportion without heart disease decreased to 32 per cent for those initially with failure and/or pericarditis. In cases with pre-existing heart disease, the prognosis was poor. Forty per cent of those initially without pericarditis or failure and only 11 per cent of those with pericarditis and/or failure were without heart disease at 10 years. 5. Mitral stenosis, uncommon at 5 years, was definitely diagnosed in 18 of the 347 cases examined at 10 years and in 7 of the 19 deaths from rheumatic fever and rheumatic heart disease. The prevalence of this complication increased with the severity of the cardiac status at start of treatment and was greater in females than in males. 6. Retreated recurrences of rheumatic fever in cases without pre-existing heart disease worsened the prognosis but did not increase the prevalence of mitral stenosis. Patients surviving an initial attack of rheumatic fever without residual heart disease do develop heart disease following a retreated recurrence. The effect of initial cardiac status on, the recurrence rate could not be determined. 7. Sex affected the outcome at 10 years. Rheumatic fever in its milder grades had a worse prognosis, and mitral stenosis was more common in females than in males. 8. These results make clear that the status of the heart of the patients at the start of treatment, the rate of recurrence of acute rheumatic fever, and the sex of the subjects must all be taken closely into account in the evaluation of any treatment of acute rheumatic fever.
Radionuclide Lung Imaging in Respiratory Decompression Sickness
Authors: MAJDI M. RADAIDEH, LAMK M. LAMKI, BRUCE J. BARRON, SHEHAB M. ELSHAZLY
Journal: Clinical Nuclear Medicine (2001)

Of the more than 3.5 million trained divers in the United States, many will experience various illnesses specific to divers. Most of these illnesses are related to the changes in absolute pressure that divers experience while diving. During and after ascent, a diver is at risk for decompression sickness and pulmonary barotrauma. A very rare casualty is pulmonary decompression sickness from immersion. This is a literature review and case report of a young woman with acute respiratory decompression sickness who had defects on perfusion lung imaging after a diving accident and after hyperbaric oxygen therapy. However, the perfusion defects reverted to normal in less than 24 hours. Possible explanations for the changes in the appearances of the scans are offered and discussed. This case report shows the potential utility of lung scanning in the diagnostic examination of these patients and the evaluation of the adequacy of treatment with hyperbaric oxygen therapy. A greater use of ventilation–perfusion lung scans in the treatment of such patients may establish its role more definitely.
Enhanced Surveillance of Infectious Diseases : the 2006 FIFA World Cup experience, Germany
Authors: K Schenkel, C Williams, T Eckmanns, G Poggensee, J Benzler, J Josephsen, G Krause
Journal: Eurosurveillance (2006)

The 2006 FIFA World Cup was held in 12 German cities between 9 June and 9 July 2006. We identified a need to accelerate and sensitise the pre-existing surveillance system for infectious diseases in order to timely detect adverse health events during the World Cup. Enhanced surveillance, based on Germany’s pre-existing system of mandatory notifications was conducted between 7 June and 11July 2006 in the 12 World Cup cities by: accelerating frequency of electronic data transmission of case-definition based notifiable diseases from weekly to daily transmission, additional reporting of non-case definition-based infectious disease events, lay and expert press screening and intensifying communication between all stakeholders of the surveillance system. Median delay of notification data transmission from the community to the federal level was reduced from three days to one day. The enhanced reporting system detected a norovirus outbreak in the International Broadcast Centre in Munich with 61 epidemiologically linked cases within the first week after onset, as well as four single cases related to the World Cup, two of them with relevance for the International Health Regulations. After the World Cup, all surveillance stakeholders agreed that communication between local, state and federal levels had improved considerably. Unlike the majority of health planners of previous mass gatherings in the last decade we did not introduce syndromic surveillance. Nevertheless, enhancement of infectious disease surveillance successfully detected adverse health events in a timely manner during the FIFA World Cup. Additionally, it provided a valuable communication and networking exercise for potentially critical health-related events. We recommend continuing daily notification data transmission for routine infectious disease surveillance in Germany.
Abstract #4696: Indolequinone antitumor agents: In vitro and in vivo cytotoxicity against human pancreatic cancer
Authors: Chao Yan, Biehuoy Shieh, Phillip Reigan, Zhiyong Zhang, Marie Colucci, Aurelie Chilloux, Jeffery Newsome, David Siegel, Dan Chan, Christopher Moody, David Ross
Journal: Cancer Research (2009)

Indolequinones were previously developed in our lab as potential antitumor agents against pancreatic cancer. The objective of this study was to optimize the structure of indolequinones for improved potency and to define their mechanism of action against pancreatic cancer. Three general classes of indolequinone were synthesized consisting of 2-methyl, 2-hydroxymethyl and 2-unsubstituted derivatives with varying leaving groups at the indole 3- position. Pancreatic cancer cell lines PANC-1, MIA PaCa-2, and BxPC-3 were used to ensure effects were not cell line specific and growth inhibitory effects were measured using both MTT and clonogenic assays. Indolequinones displayed potent cytotoxicity against pancreatic tumor cells in vitro and two specific classes of indolequinone, the 2-unsubstituted and 2-hydroxymethyl classes were particularly potent agents with IC50 values in the 20-200nM range. The indolequinones induced caspase-dependent apoptosis but no DNA damage, as assessed by measurement of DNA single strand breaks and DNA crosslinks using COMET analysis, in MIA PaCa-2 cells. Selected indolequinones were also screened against the NCI-60 cell line panel to reveal the pattern of activity across various tumor types and were particularly effective against colon, renal, and melanoma cancer cells. Indolequinones also demonstrated marked activity against the MIAPaCa-2 xenograft in vivo. The spectrum of activity of indolequinones in the NCI-60 was similar to established inhibitors of thioredoxin reductase. Indolequinones of both the 2-hydroxymethyl and 2-unsubstituted classes were found to be potent inhibitors of thioredoxin reductase in MIAPaCa-2 pancreatic cancer cells at concentrations equivalent to those inducing growth inhibitory effects. Inhibition of thioredoxin reductase represents a potential novel target in pancreatic cancer and may provide a biomarker of effect of lead indolequinones in this type of cancer. (Supported by CA114441 and AICR)   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4696.
Abstract 18175: Interaction of Platelets, Leukocytes and Released Neutrophil Extracellular Traps (NETs) Promote Deep Vein Thrombosis in vivo
Authors: Marie-Luise von Bruehl, Stark Konstantin, Alexander Steinhart, Sue Chandraratne, Maria Koellnberger, Michael Lorenz, Susanne Pfeiler, Davit Manukyan, Julia Riegger, Wolfgang Bergmeier, Nigel Mackmann, Klaus Preissner, Denisa Wagner, Bernd Engelmann, Steffen Massberg
Journal: Circulation (2011)

Objective: Venous thromboembolism has a major medical impact and is the third leading cause of cardiovascular associated death. While the critical contribution of platelets to arterial thrombosis has been recognized, the mechanisms that trigger the development of deep vein thrombosis (DVT) are not yet fully understood and are believed to be mainly dependent on coagulation. Current in vivo models associated with endothelial disruption or complete stasis only incompletely reflect the pathophysiology of DVT in humans and hinder further understanding of this process. Here, we established a novel mouse model of DVT formation and assessed the dynamics of leukocyte (lc) and platelet (pt) recruitment in vivo. Methods: In our new model DVT was induced by reduction of blood flow in the inferior vena cava (IVC) (to 23.8% of baseline) in the absence of endothelial injury. Layered thrombi develop slowly over a prolonged period of time (&gt;6-12hrs) and occlude the entire IVC 24-48hrs later mimicking human venous thrombi. We observed the dynamics of pt (GPIb-/-, GPIIb-/-), lc (CX3CR1-EGFP, LysM-EGFP), and microparticle recruitment in the IVC in vivo by intravital microscopy. Results: Using corresponding transgenic mice we show here that lc accumulation required endothelial P-selectin, and, besides monocytes, consisted mainly of neutrophils which contribute to DVT development by NET release. In addition to innate immune cells, pts are indispensable for the initiation of venous thrombosis. Further, using low-TF and hTF mice we demonstrate that blood derived tissue factor (TF), exposed on NETs and microparticles, creates a procoagulatory environment that is supported by pt adhesion and activation. The intrinsic pathway of coagulation is also involved in DVT formation, since a factor XIIa inhibitor markedly impaired DVT development. Conclusion: Together, venous thrombosis in our model is driven by a concerted interaction of pts, lcs, and the coagulation cascade. Pts bind to endothelial cells mediated by GPIbα and GPIIb-IIIa, recruited lcs, and triggered NET release thereby initiating DVT. A modulation can be attained in three different ways: by aiming on the coagulation cascade (heparins, factor inhibitors), by impairing pt function and/or by inhibiting lc activation.
Abstract 20659: Interactions Between the Second Heart Field and Neural Crest Mediate Remodeling and Functional Maturation of the Semilunar Valves.
Authors: Rajan Jain, Stacey L Rentschler, Kurt A Engleka, Lijun Yuan, Min M Lu, Jonathan A Epstein
Journal: Circulation (2010)

Cardiac defects represent the most prevalent congenital abnormality with many of these defects involving the cardiac valves. For example, bicuspid aortic valve disease affects 1-2% of the population and can lead to significant morbidity and mortality. The semilunar valves develop from embryonic endocardial cushions that contain extracellular matrix, mesenchyme derived from endothelial-mesenchymal transformation of endocardial cells, and neural crest cells. Here, we show a novel role for neural crest cells in semilunar valve remodeling. Using a series of genetically modified mouse models with second heart and/or neural crest defects, we show that abnormalities of cardiac neural crest result in dysmorphic, thickened semilunar valve leaflets that are functionally incompetent. These defects are caused by a lack of apoptosis that normally accompanies late gestation valve remodeling as well as an increase in extracellular matrix deposition. During migration to the outflow tract, we show neural crest cells inter...
Abstract 19437: Elevated Platelet Turnover in Patients Receiving Dual Antiplatlet Therapy Could Permit the Formation of Uninhibited Platelet Clusters That Act as Seeds for Thrombus Formation
Authors: Thomas Hoefer, Timothy D Warner
Journal: Circulation (2014)

Introduction: ACS patients who also have conditions associated with increased platelet turnover, such as diabetes or chronic kidney disease, are at increased risk of atherothrombotic events despite receiving dual-antiplatelet therapy (DAPT). It may well be that aspirin and thienopyridines, such as clopidogrel or prasugrel, prescribed once daily as pharmacologically short-lived but irreversibly acting agents, are less effective in these patients because of the daily emergence of a significant subpopulation of uninhibited platelets. Hypothesis: Here we investigated the potentially crucial roles of subpopulations of uninhibited platelets in overcoming DAPT and driving aggregation. Methods: Aliquots of platelet rich plasma were incubated with aspirin, prasugrel active metabolite (PAM) plus aspirin, or vehicle and platelets were differently labelled with membrane dyes. Aliquots were then combined in various proportions and platelet responses measured in standard light transmission aggregometry. Aggregates formed in response to platelet agonists were then fixed and detailed structural analyses made by advanced imaging techniques, including confocal microscopy and ImageStream flow cytometry, to determine the interactions of different platelet populations. Results: Platelet aggregation responses and images of platelet aggregates demonstrated complex, dynamic relationships between platelet subpopulations. Summary analysis indicated that aggregates containing aspirin-treated (90-60%) and drug-free (10-40%) platelets had random distributions of drug-free platelets in response to ADP or AA. In contrast, aggregates containing DAPT-inhibited (90-60%) platelets and drug-free (10-40%) platelets showed marked clustering of drug-free platelets at aggregate cores surrounded by recruited DAPT-inhibited platelets. Conclusions: We show that a subpopulation of drug-free platelets can provide seeds for the formation of aggregates that then recruit DAPT-inhibited platelets. Such interaction between platelet subpopulations are of direct relevance to ACS patients with underlying conditions associated with elevated platelet turnover and may well provide an explanation for the failure of DAPT with aspirin and thienopyridines.
Revealing the Generation of Human Memory Stem T Cells in Haploidentical T-Replete Hematopoietic Stem Cell Transplantation
Authors: Nicoletta Cieri, Giacomo Oliveira, Raffaella Greco, Mattia Forcato, Cristian Taccioli, Veronica Valtolina, Maddalena Noviello, Luca Vago, Attilio Bondanza, Francesca Lunghi, Sarah Marktel, Laura Bellio, Claudio Bordignon, Silvio Bicciato, Jacopo Peccatori, Fabio Ciceri, Chiara Bonini
Journal: Blood (2014)
Statistics notes: Transformations, means, and confidence intervals
Authors: J M. Bland, D. G Altman
Journal: BMJ (1996)

When we use transformed data in analyses,1 this affects the final estimates that we obtain. Figure 1 shows some serum triglyceride measurements, which have a skewed distribution. A logarithmic transformation is often useful for data which have positive skewness like this, and here the approximation to a normal distribution is greatly improved. For the untransformed data the mean is 0.51 mmol/l and the standard deviation 0.22 mmol/l. The mean of the log10 transformed data is -0.33 and the standard deviation is 0.17. If we take the mean on the transformed scale and back transform by taking the antilog, we get …
Abstract 18703: Impact of the 2014 Atrial Fibrillation Guideline on the Proportion of Patients Recommended for Oral Anticoagulation
Authors: Emily C O’Brien, Sunghee Kim, Paul L Hess, James V Freeman, Laine Thomas, Gregg C Fonarow, Jack E Ansell, Peter R Kowey, Elaine M Hylek, Kenneth W Mahaffey, Paul Chang, Jonathan P Piccini, Eric D Peterson
Journal: Circulation (2014)

Introduction: In 2014, the AHA/ACC/HRS published new atrial fibrillation (AF) treatment guidelines recommending use of a refined stroke risk score and revised threshold for oral anticoagulation (OAC) initiation. Methods: Using data from ORBIT-AF, an ongoing, national, outpatient AF registry conducted at 176 sites, we examined changes in the number of patients qualifying for OAC based on clinical stroke risk scores under 2011 ACCF/AHA/HRS versus 2014 AHA/ACC/HRS guidelines. Patients were considered recommended for OAC under the 2011 guideline with a CHADS2 score &gt;=2 and under the 2014 guideline with a CHA2DS2-VASC score &gt;=2. We reported the fraction of patients treated with OAC (warfarin or dabigatran) among patients qualifying for OAC under each guideline. Results: From 2009 - 2010, 10132 patients were enrolled in ORBIT-AF (median age [IQR] = 75 years [67 - 82]; 42.3% female). The proportion of patients qualifying for OAC increased from 71.8% under the 2011 guideline to 90.8% under the 2014 guideline (Figure). For patients under the age of 65, the proportion qualifying for treatment with OAC increased from 43.1% to 60.6%. Similar increases were observed for patients over the age of 65: 79.1% indicated for OAC under the 2011 guideline, compared with 98.5% under the 2014 guideline. There were 97.7% of women who qualified for OAC under the 2014 guideline, compared with 76.7% under the 2011 guideline. The fraction of indicated patients who were not receiving OAC increased under the 2014 guideline (21.9% vs. 19.9% under the 2011 guideline), with the highest undertreatment rates for patients younger than 65 (25.4%). Conclusions: The 2014 AF treatment guideline substantially increased the proportion of patients who qualified for OAC, with near-universal indication for women and for patients older than 65. Under the 2014 guideline, approximately 22% of the indicated patients in our community-based cohort did not receive OAC.
The Irradiation of Transplanted Bagg-Jacksen and Yale Carcinomas in Mice, as Affected by Diet and Foster Nursing
Authors: Jules A. Plaut, Robert Tennant, Ashley W. Oughterson
Journal: Cancer Research (1942)

It is common clinical experience that tumors do not respond uniformly to x-ray. Some of the factors associated with this varied response are known (Stewart and others). It is well established that the cell type, size, and location of a tumor are important considerations in determining its radiosensitivity, al though even these factors do not appear to be invariably reliable. While attention has been directed chiefly to the morphology, size, and location of the tumor, it has become apparent that there are other more important and still unknown factors which determine the radiosensitivity. Previous experiments (6, 8) indicate that the host or the interaction of host and tumor play an important role in determining the response of the tumor to irradiation. It was found that when a mal ignant mammary adenocarcinoma was transplanted into the parent strain (A albino) and treated with a single dose of 2,5oo r no cures were obtained. When the same tumor was transplanted into an F2 hybrid (AC57) 8o per cent cures were obtained. In both instances the tumor took in Ioo per cent of the animals. In the parent stock there were no regressions. The conclusion from these experiments was that x-ray augmented the natural resistance of the host. Whatever the host-tumor relation may have been, it appeared that x-ray brought to light these latent factors. The present experiments were designed to extend these observations and determine whether other factors said to influence the development of tumors or their growth would also change the response of the tumor to x-ray. The following experiments were planned. One of the objections to postulating increased radiosensitivity of the tumor in the F2 generation was that some type of foreign protein reaction might be responsible. Thus the summation of x-ray damage plus such
Mutational Analysis of Patients with Primary Resistance to Single-Agent Ibrutinib in Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Authors: Sriram Balasubramanian, Michael Schaffer, William Deraedt, Cuc Davis, Emily Stepanchick, Regina Aquino, Zhilong Yuan, Britte Kranenburg, Irit Avivi, Martin Dreyling, Simon Rule, Michael Wang, Sen Hong Zhuang, Aleksandra Rizo, Georg Lenz
Journal: Blood (2014)
Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients
Authors: RL Comenzo, E Vosburgh, RW Simms, P Bergethon, D Sarnacki, K Finn, S Dubrey, DV Faller, DG Wright, RH Falk, M Skinner
Journal: Blood (1996)