tbuckley/cabot-search huggingface dataset:
SUBCUTANEOUS REACTION OF RABBITS TO HORSE SERUM
Authors: J. H. Mason Knox, W. L. Moss, G. L. Brown
Journal: The Journal of Experimental Medicine (1910)

1. Anaphylaxis or allergy of rabbits against horse serum can be proved by subcutaneous test. 2. The test is best made in the following way. The skin of the animal, preferably of the abdomen or flank, is shaved. (This should be done a few hours before the injection.) The injection is made by means of a small hypodermic syringe and intradermally. An effort was made not to inject the serum under the skin. Those injections were considered most favorable by which the serum remained as a small bleb in the skin proper. Undiluted horse serum was used for most of the experiments. The amount injected varied from 0.0I cubic centimeter to I cubic centimeter. The reaction seemed as definite after 0.0I cubic centimeter as after a larger quantity. See PDF for Structure 3. The specific reaction appears in from twelve to twenty-four hours after the test is made and reaches its maximum in from twenty-four to thirty-six hours. It consists of a local swelling extending from 0.5 to 2 centimeters from the point of inoculation. The skin involved in the raised area is usually red and hotter than the surrounding skin. Macroscopically and microscopically the reacting area has the appearance of a local acute inflammation. 4. The altered reactivity (allergy) or hyper-susceptibility (anaphylaxis) sets in usually in from ten to fifteen days after the first injection of horse serum, and lasts at least three months. Individual rabbits show marked variation from the average time of the development of anaphylaxis. 5. The appearance of precipitines against horse serum in the blood of rabbits appears nearly synchronously with the allergic condition. 6. After large injections of serum the allergic rabbits still react subcutaneously. A suppression of allergy which would correspond to the so-called anti-anaphylaxis could not be proved. 7. Also in regard to the offspring of injected rabbits the subcutaneous test was not positive. The young of these rabbits did not develop a more active allergy than the young of normal rabbits. 8. Neither the injection of considerable quantities of horse serum nor the development of a marked local reaction in the skin after intradermal inoculations of horse serum in a sensitized rabbit is accompanied or followed by greater variations in the number or types of leucocytes in the circulating blood than is found in control animals.
Doctors’ leaders call for warning system for GP burnout
Authors: Adrian O’Dowd
Journal: BMJ (2015)

General practice needs its own system that allows for “distress signals” when GPs are dangerously tired and overloaded, doctors’ leaders have said, to help ensure that patient safety issues do not arise.

The Royal College of General Practitioners launched a consultation document on 29 July,1 in which it made several proposals for protecting GPs’ wellbeing to prevent them becoming too exhausted to provide safe care.

GP fatigue is …
Abstract 329: T2-weighted MRI Has High Diagnostic Accuracy for Myocardial Hemorrhage in Myocardial Infarction: A Preclinical Validation Study in Swine
Authors: Alexander R Payne, Colin Berry, Peter Kellman, Rachel Anderson, Marcus Y Chen, Stuart Watkins, Alan R McPhaden, William Schenke, Victor Wright, Robert J Lederman, Anthony H Aletras, Andrew E Arai
Journal: Circulation (2009)

Background:  Myocardial hemorrhage after myocardial infarction (MI) frequently goes undetected. Since the paramagnetic effects of oxidized iron may result in signal loss on T2* and T2-weighted MRI, we investigated the diagnostic accuracy of T2-weighted MRI in experimental MI.   Methods:  Acute MI was created in swine (43±9.5 kg) by occluding the left anterior descending coronary artery (n=10) or circumflex (n=5) for 90 minutes followed by reperfusion for ≤3 days (n=2), 10 days (n=7) or 60 days (n=6). Cardiac MRI was performed at 1.5T using T2-prepared steady-state free-precession (T2P-SSFP) and gadolinium enhanced (CE) MRI. Left ventricular (LV) sections were visually inspected, photographed and stained for histology. Gross images and histology were scored for myocardial hemorrhage by an experienced cardiac pathologist blinded to all other data. Regions of low signal intensity on T2-weighted and CE-MRI were independently determined by 3 cardiologists blinded to the pathology results. All images were de-identified and analyzed in random order.   Results:  Eighty ventricular slices of pathology were matched with MRI (n=68 for first pass CE-CMR). All pathologic sections with evidence of MI (n=63 (79%)) also exhibited hyperintense zones consistent with edema on T2-weighted, and infarct on CE-MRI. Myocardial hemorrhage occurred in 49 LV sections (61%) and corresponded with signal voids on 48 T2-weighted (98%) and 26 CE-MRI (53%). Alternatively, signal voids occurred in the absence of hemorrhage in 3 T2-weighted (90% specificity) and 5 CE-MRI (84% specificity). On first pass CE-MRI, 27/43 perfusion defects corresponded with hemorrhage (63% sensitivity) while 5/25 defects occurred in the absence of hemorrhage (80% specificity). The positive and negative predictive values for pathological evidence of hemorrhage were 94% & 96% for T2-weighted, 84% & 53% for CE-MRI, and 84% & 56% for first pass perfusion.   Conclusions:  T2-weighted MRI has high diagnostic accuracy for myocardial hemorrhage. Heterogeneity of signal intensity associated with acute MI on T2-weighted MRI is partially due to intramyocardial hemorrhage.
Rectal Optical Markers for <i>In Vivo</i> Risk Stratification of Premalignant Colorectal Lesions
Authors: Andrew J. Radosevich, Nikhil N. Mutyal, Adam Eshein, The-Quyen Nguyen, Bradley Gould, Jeremy D. Rogers, Michael J. Goldberg, Laura K. Bianchi, Eugene F. Yen, Vani Konda, Douglas K. Rex, Jacques Van Dam, Vadim Backman, Hemant K. Roy
Journal: Clinical Cancer Research (2015)

Colorectal cancer remains the second leading cause of cancer deaths in the United States despite being eminently preventable by colonoscopy via removal of premalignant adenomas. In order to more effectively reduce colorectal cancer mortality, improved screening paradigms are needed. Our group pioneered the use of low-coherence enhanced backscattering (LEBS) spectroscopy to detect the presence of adenomas throughout the colon via optical interrogation of the rectal mucosa. In a previous ex vivo biopsy study of 219 patients, LEBS demonstrated excellent diagnostic potential with 89.5% accuracy for advanced adenomas. The objective of the current cross-sectional study is to assess the viability of rectal LEBS in vivo.
Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen
Authors: Innocent Safeukui, Pierre A. Buffet, Guillaume Deplaine, Sylvie Perrot, Valentine Brousse, Alioune Ndour, Marie Nguyen, Odile Mercereau-Puijalon, Peter H. David, Geneviève Milon, Narla Mohandas
Journal: Blood (2012)
Transient outward current in human ventricular myocytes of subepicardial and subendocardial origin.
Authors: E Wettwer, G J Amos, H Posival, U Ravens
Journal: Circulation Research (1994)

In various mammalian species, shapes of action potentials vary within the cardiac wall because of differences in transient outward current (Ito). A prominent Ito exists in human ventricular myocytes, but cells have not been separated according to their original localization. Human ventricular myocytes were isolated from separated subepicardial and subendocardial tissue, and regional variations in Ito were studied. Ito was larger in subepicardial than subendocardial cells. Current density at +60 mV was 7.9 +/- 0.7 pA/pF (n = 28) in subepicardial cells and 2.3 +/- 0.3 pA/pF (n = 16) in subendocardial cells. When cells from explanted failing and nonfailing donor hearts were compared, Ito was not different in subepicardial cells; however, it was larger in subendocardial cells from nonfailing hearts. The potential of half-maximal activation (V0.5) was more positive in subendocardial cells (+25.6 +/- 3.5 mV, n = 15) than in subepicardial cells (+9.2 +/- 1.8 mV, n = 28). There was no difference in V0.5 between cells from failing and nonfailing hearts. Ito inactivation was similar in all cell types and independent of membrane depolarization (time constant [tau] = approximately 60 milliseconds at 22 degrees C). The potential of half-maximal steady-state inactivation was similar in all cell types. Recovery from inactivation of Ito was fast in subepicardial cells at -100 mV (tau = 24 +/- 4 milliseconds, n = 6), exceeding control values transiently (overshoot), and slow at -40 mV without overshoot (tau = 638 +/- 91 milliseconds, n = 6). In subendocardial cells, Ito recovered at -100 mV with a fast phase (tau = 25 milliseconds) and a slow phase (tau = 328 milliseconds), and recovery was not complete after 6 seconds at -100 mV. In conclusion, regional differences in Ito between subepicardial and subendocardial cells may have clinical implications with respect to rhythmic disturbance during heart failure.
Gene Expression, Molecular Class Changes, and Pathway Analysis after Neoadjuvant Systemic Therapy for Breast Cancer
Authors: Ana M. Gonzalez-Angulo, Takayuki Iwamoto, Shuying Liu, Huiqin Chen, Kim-Anh Do, Gabriel N. Hortobagyi, Gordon B. Mills, Funda Meric-Bernstam, W. Fraser Symmans, Lajos Pusztai
Journal: Clinical Cancer Research (2012)

To examine gene expression differences between pre- and post-neoadjuvant systemic therapy (NST) specimens of breast cancers and identify biologic changers that may lead to new therapeutic insights.Gene expression data from prechemotherapy fine needle aspiration specimens were compared with resected residual cancers in 21 patients after 4 to 6 months of NST. We removed stroma-associated genes to minimize confounding effects. PAM50 was used to assign molecular class. Paired t test and gene set analysis were used to identify differentially expressed genes and pathways.The ER and HER2 status based on mRNA expression remained stable in all but two cases, and there were no changes in proliferation metrics (Ki67 and proliferating cell nuclear antigen expression). Molecular class changed in 8 cases (33.3%), usually to normal-like class, which was associated with low residual cancer cell cellularity. The expression of 200 to 600 probe sets changed between baseline and post-NST samples. In basal-like cancers, pathways driven by increased expression of phosphoinositide 3-kinase, small G proteins, and calmodulin-dependent protein kinase II and energy metabolism were enriched, whereas immune cell-derived and the sonic hedgehog pathways were depleted in residual cancer. In non-basal-like breast cancers, notch signaling and energy metabolism (e.g., fatty acid synthesis) were enriched and sonic hedgehog signaling and immune-related pathways were depleted in residual cancer. There was no increase in epithelial-mesenchymal transition or cancer stem cell signatures.Our data indicate that energy metabolism related processes are upregulated and immune-related signals are depleted in residual cancers. Targeting these biologic processes may represent promising adjuvant treatment strategies for patients with residual cancer.
Recommendations for an Effective Follow-Up Strategy in Melanoma Patients Should Be Tailored to the Investigations Performed During Initial Staging
Authors: Philippe Saiag
Journal: Journal of Clinical Oncology (2003)

During Initial StagingTo the Editor: In a recent paper, Garbe et al 1 have published an impressive study of 2,008 consecutive patients with stage I to IV cutaneous melanoma who were prospectively followed up during a "window period" of 25 months with regular clinical, lymph node, and liver sonographies and chest x-ray evaluations.This is truly the first prospective cohort study conducted so far that evaluates the various procedures used in the follow-up of patients with cutaneous melanoma.Recommendations for an effective follow-up strategy are outlined, which are for the first time based on a correctly designed study.However, despite the numerous figures given in the paper, I was unable to calculate the false-negative rate of this follow-up strategy because information on the outcome of patients at the end of the study window period is missing.Whether some patients without progression at their last follow-up visit experienced melanoma progression before the next scheduled visit outside the study period should be detailed.I was also unable to precisely delineate individually the value of each recommended evaluation procedure.This information is of importance; follow-up strategies may vary with time.For example, patients with negative sentinel lymph node biopsy have a considerably reduced probability of lymph node progression, 2 and it would be interesting to estimate the value of follow-up with lymph node sonography in such patients.At least for clinical evaluation, lymph-node sonography, and blood tests (which are recommended procedures for patients with stage I or II melanomas), the total number of true positives, false positives, true negatives and false negatives (the latter being defined by occurrence of progression before the next scheduled follow-up visit) should be published.Such information should be easily extracted from the huge database constructed for this study.
Down's syndrome and acute leukemia in children: an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction [see comments]
Authors: S Kojima, T Matsuyama, T Sato, K Horibe, S Konishi, M Tsuchida, Y Hayashi, H Kigasawa, Y Akiyama, J Okamura
Journal: Blood (1990)
Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels
Authors: Suzanne Jones, Clifford J. Holmes, Raymond T. Krediet, Ruth Mackenzie, Dirk Faict, Anders Tranaeus, John D. Williams, Gerald A. Coles, Nicholas Topley, None on behalf of the BICARBONATE/LACTATE STUDY GROUP
Journal: Kidney International (2001)
Respiratory applications of telemedicine
Authors: C. B Cooper
Journal: Thorax (2009)

Dramatic advances in electronic communications have expanded access to information and contributed vastly to global human knowledge and understanding. At the same time, electronic acquisition, processing, storage and transmission of data is rapidly becoming an integral part of modern health care. The potential seems boundless. The electronic medical record has the ability to improve the reliability and completeness of individual healthcare information and should therefore facilitate continuity of care between healthcare providers and minimise human errors. At the same time, legislators have seen the absolute necessity to respect privacy in handling protected health information.1

A promising application of electronic data transmission in healthcare development and delivery is telemedicine.2 Telemedicine has evolved from the development of synchronous data modalities, through data transfer and storage, towards automated decision making and robotics.3 One recent review article4 analysed 104 published articles on telemedicine in order to develop an operational definition. The authors concluded that telemedicine is a branch of e-health that uses communications networks for delivery of healthcare services and medical education from one geographical location to another. Although more than 50% of published articles on telemedicine originate from the USA,3 telemedicine has the potential to advance healthcare delivery in developing or underserved regions of the world by concentration of expertise in special centres and dissemination of services through information technologies. Teleradiology, for example, enables radiographs and CT scans to be read at remote specialised centres in other countries.5 Approaches such as this should not only make services more widely accessible, but should also enhance the uniformity of quality of services throughout populations.

As telemedicine finds its way into mainstream medical practice, a number of …
New developments in the chemistry and biology of the bioactive constituents of tanshen
Authors: Xihong Wang, Susan L. Morris‐Natschke, Kuo‐Hsiung Lee
Journal: Medicinal Research Reviews (2006)

Abstract Tanshen, the rhizome of Salvia miltiorrhiza Bunge, has been used in Chinese traditional medicine (TCM) for multiple therapeutic remedies. The major constituents of Tanshen include water‐soluble phenolic acids and lipophilic tanshinones. Phenolic acids possess antioxidant and anticoagulant activities, whereas tanshinones show antibacterial, antioxidant, and antineoplastic activities. This review will focus on recent developments concerning the chemical constituents of Tanshen and their biological activities. These chemical and biological studies continue to increase our understanding about a scientific basis for the traditional clinical use of Tanshen and can also contribute to the development of new drug candidates. Recently, in the author's laboratory, a new compound, neo‐tanshinlactone, was discovered to have potent selective antibreast cancer activity. This compound might serve as a lead for developing promising antibreast cancer clinical trials candidates. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 1, 133–148, 2007
Initial starting dose of inhaled corticosteroids in adults with asthma: a systematic review
Authors: H Powell
Journal: Thorax (2004)

<b>Background:</b> Asthma guidelines vary in their recommendations for the initial dose of inhaled corticosteroid (ICS) in asthma. A systematic review of the literature was conducted to establish the optimal starting dose of ICS for asthma in adults. <b>Methods:</b> Randomised controlled trials comparing two doses of the same ICS in adults with asthma and no concomitant inhaled or oral corticosteroid were assessed. Included trials were analysed according to the following ICS dose comparisons: high (⩾800 μg/day beclomethasone (BDP)) versus moderate (400&lt;800 μg/day BDP) (n = 7); moderate versus low (&lt;400 μg/day BDP) (n = 6); step down versus constant dose (n = 4). <b>Results:</b> Fourteen publications describing 13 trials were included in the review. Studies (n = 4) that compared a step down approach with a constant moderate/low dose of ICS found no difference in lung function, symptoms, or rescue medications between the two treatment approaches (p&gt;0.05). There was no difference in the change in morning peak flow after treatment with high compared with moderate dose ICS. When compared with low dose ICS, moderate dose ICS significantly improved morning peak flow (change from baseline WMD 11.14 l/min, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD −0.29, 95% CI −0.53 to −0.06). <b>Conclusions:</b> For patients with asthma who require ICS, starting with a moderate dose is equivalent to starting with a high dose and stepping down. The small non-significant benefits of starting with a high ICS dose are not of sufficient clinical benefit to warrant its use. Initial moderate ICS doses appear to be more effective than an initial low ICS dose.
Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2
Authors: Runping Liu, Renping Zhao, Xiqiao Zhou, Xiuyin Liang, Deanna J.W. Campbell, Xiaoxuan Zhang, Luyong Zhang, Ruihua Shi, Guangji Wang, William M. Pandak, Alphonse E. Sirica, Phillip B. Hylemon, Huiping Zhou
Journal: Hepatology (2014)

Cholangiocarcinoma (CCA) is an often fatal primary malignancy of the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, the specific mechanisms by which bile acids may be acting to promote cholangiocarcinogenesis and invasive biliary tumor growth have not been fully established. Recent studies have shown that CBAs, but not free bile acids, stimulate CCA cell growth, and that an imbalance in the ratio of free to CBAs may play an important role in the tumorigenesis of CCA. Also, CBAs are able to activate extracellular signal-regulated kinase (ERK)1/2- and phosphatidylinositol-3-kinase/protein kinase B (AKT)-signaling pathways through sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes. In the current study, we demonstrate S1PR2 to be highly expressed in rat and human CCA cells, as well as in human CCA tissues. We further show that CBAs activate the ERK1/2- and AKT-signaling pathways and significantly stimulate CCA cell growth and invasion in vitro . Taurocholate (TCA)-mediated CCA cell proliferation, migration, and invasion were significantly inhibited by JTE-013, a chemical antagonist of S1PR2, or by lentiviral short hairpin RNA silencing of S1PR2. In a novel organotypic rat CCA coculture model, TCA was further found to significantly increase the growth of CCA cell spheroidal/“duct-like” structures, which was blocked by treatment with JTE-013. Conclusion : Our collective data support the hypothesis that CBAs promote CCA cell-invasive growth through S1PR2. (Hepatology 2014;60:908–918)
Evidence-Based Psychological Treatments: An Update and a Way Forward
Authors: David H. Barlow, Jacqueline R. Bullis, Jonathan S. Comer, Amantia A. Ametaj
Journal: Annual Review of Clinical Psychology (2012)

Enormous progress in the field of clinical science has been made over the past 50 years, with advances in our understanding of psychopathology and more sophisticated research methodology leading to the development of more efficacious psychological treatments for a variety of behavioral disorders. Despite these advances, the public health impact of well-established psychological treatments is less than it should be. After an overview of the current status of the field, we identify barriers that must be overcome to maximize the public health impact and propose that to breach these barriers we must (a) augment the efficacy of treatments, (b) broaden the impact of treatments across diagnoses to include temperamental variables, (c) attend more closely to mechanisms of action of treatments, and (d) learn the best methods for disseminating and implementing psychological interventions. We conclude by proposing new directions in both research and clinical practice to accomplish these goals.
Quality of Life Differences Between Responders and Nonresponders in the Treatment of Cutaneous Lupus Erythematosus
Authors: Aileen Y. Chang, Elizabeth Ghazi, Joyce Okawa, Victoria P. Werth
Journal: JAMA Dermatology (2013)

safe skin practices, including sun avoidance and SSE.Safe skin practices are as important as regular exercise and smoking cessation and should be included in routine health education counseling.With evidence suggesting the importance of SSE, it is concerning that most of the Hispanic participants did not report performing them.Physicians should educate their patients, demonstrate for them how to perform a proper SSE, explain what to look for, and provide resources with examples.Physicians should also teach their Hispanic patients to pay particular attention to acral areas and extremities because there is a higher incidence of melanoma on those areas in Hispanics. 2