tbuckley/cabot-search huggingface dataset:
Cathelicidin Peptide Sheep Myeloid Antimicrobial Peptide-29 Prevents Endotoxin-induced Mortality in Rat Models of Septic Shock
Authors: Andrea Giacometti, Oscar Cirioni, Roberto Ghiselli, Federico Mocchegiani, Giuseppina D'Amato, Raffaella Circo, Fiorenza Orlando, Barbara Skerlavaj, Carmela Silvestri, Vittorio Saba, Margherita Zanetti, Giorgio Scalise
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The present study was designed to investigate the antiendotoxin activity and therapeutic efficacy of sheep myeloid antimicrobial peptide (SMAP)-29, a cathelicidin-derived peptide. The in vitro ability of SMAP-29 to bind LPS from Escherichia coli 0111:B4 was determined using a sensitive limulus chromogenic assay. Two rat models of septic shock were performed: (1) rats were injected intraperitoneally with 1 mg E. coli 0111:B4 LPS and (2) intraabdominal sepsis was induced via cecal ligation and single puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1 mg/kg SMAP-29, 1 mg/kg polymyxin B or 20 mg/kg imipenem. The main outcome measures were: abdominal exudate and plasma bacterial growth, plasma endotoxin and tumor necrosis factor-alpha concentrations, and lethality. The in vitro study showed that SMAP-29 completely inhibited the LPS procoagulant activity at approximately 10 microM peptide concentration. The in vivo experiments showed that all compounds reduced the lethality when compared with control animals. SMAP-29 achieved a substantial decrease in endotoxin and tumor necrosis factor-alpha plasma concentrations when compared with imipenem and saline treatment and exhibited a slightly lower antimicrobial activity than imipenem. No statistically significant differences were noted between SMAP-29 and polymyxin B. SMAP-29, because of its double antiendotoxin and antimicrobial activities, could be an interesting compound for septic shock treatment.
Human T Cells Armed with Her2/neu Bispecific Antibodies Divide, Are Cytotoxic, and Secrete Cytokines with Repeated Stimulation
Authors: Ryan C. Grabert, Leslie P. Cousens, Janelle A. Smith, Sarah Olson, Jonathan Gall, Wendy B. Young, Pamela A. Davol, Lawrence G. Lum
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Cancer immunotherapy has been limited by anergy of patient T cells, inadequate numbers of precursor tumor-specific CTL, and difficulty in producing therapeutic doses of CTL. To overcome these limitations, bispecific antibodies have been used to create artificial antibody receptors that direct polyclonal activated T cells (ATC) to target tumor antigens. Studies reported herein were designed to characterize bispecific antibody–armed ATC functions during multiple rounds of targeted cell stimulation. Experimental Design: ATCs were generated from human peripheral blood mononuclear cells (PBMC) by culture with anti-CD3 and interleukin 2 for 14 days and armed with anti-CD3 × anti-Her2 bispecific antibody (Her2Bi). In vitro, Her2Bi-armed ATC were examined for a range of functions after repeated stimulation with the Her2/neu-expressing breast cancer cell line SK-BR-3. PBMC isolated from cancer patients treated with Her2Bi-armed ATC were tested ex vivo for cytotoxicity against SK-BR-3. Results: In vitro, armed ATC divided, maintained surface Her2Bi, and expressed a range of activities for extended periods of time. Perforin-mediated cytotoxic activity by armed ATC continued for at least 336 hours, and cytokines and chemokines (i.e., IFN-γ and regulated on activation, normal T-cell expressed and secreted protein [RANTES]) were secreted during successive rounds of stimulation. Furthermore, PBMC isolated from patients over their courses of immunotherapy exhibited significant cytolytic activity against SK-BR-3 as a function of Her2Bi-armed ATC infusions. Conclusions: These studies show that armed ATC are specific, durable, and highly functional T-cell populations in vitro. These previously unappreciated broad and long-term functions of armed ATC are encouraging for their therapeutic use in treating cancer.
Some Results of Treatment by X Rays, High-Frequency Currents, and Ultraviolet Rays, with Illustrative Cases
Authors: J. A. Codd
Journal: BMJ (1904)

branny scales.She suffered no pain.She sought treatment now only because she thought It was beginning to spread, and becoming more unsightly.On December 218t, 1903, 5 milligrams of radium bromide were applied in direct contact witha the patch.There was no discharge from the sore in this as in the former case which could in any way diminish the radio-activity of the specimen employed.Between December 2 1St, 1903, and March xs8th, 1904, sixty-one applications were given.First month five applications weekly of ten minutes' duration, without manifesting any visible clhange, excepting a slight redness.Second month twenty applications of thirty minutes' duration were given, the redness of margin becoming more pronounced, accompanied by itching, but no discharge.February I3th, the duration of the application was increased to forty-five minutes, of which fifteen such applications were given, with the result that the edges of the patch be- came Ewalien with the sensation of pins and needles in the part, and a dislharge on pressure.Treatment was still continued, and six further applications were given of sixly minutes each, the last on March i8th, when the treatment was stopped.A week later the pain, swelling, and discharge had diminished.The base of the ulcer was clean and healthy-looking, but the edges somewhat raised.No treatment or external applications of any kind were applied prior to, during, or since the treatment mentioned. REMARKS.Radium, to be of practical use in the cure of disease or the alleviation of human suffering must be forthcoming in much larger quantities, of a recognized standard of activity, and at a verv much cheaper rate.From my own experience of the metal, I prefer detailing what I have already achieved, and how I achieved it, rather than expressing an opinion on its merits which might in any way circumscribe its sphere-of application or prevent others from putting it to the test.For diagnostic purposes it is very doubtful indeed if radium can ever be of much use.With the x rays we have much grounds for hope in both lupus and rodent ulcer, and, com- bined with Finsen light, the results recorded are becoming more universal and more reassuring.In my previous paper I expressed the belief that the Finsen light for circumscribed superficial lupus had no equal.Now, after eighteen months' further experience, I am more convinced than ever of its efficacy, but it will be for you, ladies and gentlemen, to say whether or not I have claimed for the method more than my results justify.
Combined Screening With Ultrasound and Mammography vs Mammography Alone in Women at Elevated Risk of Breast Cancer
Authors: Wendie A. Berg
Journal: JAMA (2008)

Screening ultrasound may depict small, node-negative breast cancers not seen on mammography.To compare the diagnostic yield, defined as the proportion of women with positive screen test results and positive reference standard, and performance of screening with ultrasound plus mammography vs mammography alone in women at elevated risk of breast cancer.From April 2004 to February 2006, 2809 women, with at least heterogeneously dense breast tissue in at least 1 quadrant, were recruited from 21 sites to undergo mammographic and physician-performed ultrasonographic examinations in randomized order by a radiologist masked to the other examination results. Reference standard was defined as a combination of pathology and 12-month follow-up and was available for 2637 (96.8%) of the 2725 eligible participants.Diagnostic yield, sensitivity, specificity, and diagnostic accuracy (assessed by the area under the receiver operating characteristic curve) of combined mammography plus ultrasound vs mammography alone and the positive predictive value of biopsy recommendations for mammography plus ultrasound vs mammography alone.Forty participants (41 breasts) were diagnosed with cancer: 8 suspicious on both ultrasound and mammography, 12 on ultrasound alone, 12 on mammography alone, and 8 participants (9 breasts) on neither. The diagnostic yield for mammography was 7.6 per 1000 women screened (20 of 2637) and increased to 11.8 per 1000 (31 of 2637) for combined mammography plus ultrasound; the supplemental yield was 4.2 per 1000 women screened (95% confidence interval [CI], 1.1-7.2 per 1000; P = .003 that supplemental yield is 0). The diagnostic accuracy for mammography was 0.78 (95% CI, 0.67-0.87) and increased to 0.91 (95% CI, 0.84-0.96) for mammography plus ultrasound (P = .003 that difference is 0). Of 12 supplemental cancers detected by ultrasound alone, 11 (92%) were invasive with a median size of 10 mm (range, 5-40 mm; mean [SE], 12.6 [3.0] mm) and 8 of the 9 lesions (89%) reported had negative nodes. The positive predictive value of biopsy recommendation after full diagnostic workup was 19 of 84 for mammography (22.6%; 95% CI, 14.2%-33%), 21 of 235 for ultrasound (8.9%, 95% CI, 5.6%-13.3%), and 31 of 276 for combined mammography plus ultrasound (11.2%; 95% CI. 7.8%-15.6%).Adding a single screening ultrasound to mammography will yield an additional 1.1 to 7.2 cancers per 1000 high-risk women, but it will also substantially increase the number of false positives.clinicaltrials.gov Identifier: NCT00072501.
Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1 mismatch repair genes: implications for genetic testing
Authors: M Cravo
Journal: Gut (2002)

In hereditary non-polyposis colorectal cancer, over 90% of the identified mutations are in two genes, hMSH2 and hMLH1. A large proportion of the mutations detected in these genes are of the missense type which may be either deleterious mutations or harmless polymorphisms.To investigate whether nine missense and one splice site mutation of hMLH1 and hMSH2, in 10 kindreds with a familial history of colorectal cancer or young age of onset, could be interpreted as pathogenic.Clinical and genetic characteristics were collected: (i) evolutionary conservation of the codon involved; (ii) type of amino acid change; (iii) occurrence of mutation in healthy controls; (iv) cosegregation of mutation with disease phenotype; (v) functional consequences of gene variant; and (vi) microssatellite instability and immunoexpression of hMSH2 and hMLH1 analysis.Seven different missense and one splice site mutation were identified. Only 1/8 was found in the control group, 2/7 occurred in conserved residues, and 5/7 resulted in non-conservative changes. Functional studies were available for only 2/8 mutations. Segregation of the missense variant with disease phenotype was observed in three kindreds.In the majority of families included, there was no definitive evidence that the missense or splice site alterations were causally associated with an increased risk of developing colorectal cancer. Until further evidence is available, these mutational events should be regarded and interpreted carefully and genetic diagnosis should not be offered to these kindreds.
STUDY OF TRANSFUSED BLOOD
Authors: Winifred Ashby
Journal: The Journal of Experimental Medicine (1921)

Evidence is presented to show that there is no hemolytic toxin producing the anemia in pernicious anemia. Partial evidence is presented to show that the periods of active blood destruction which are seen as the exception in pernicious anemia cases during a series of transfusions are due to the activity of the blood-destroying organs of the body rather than to the intrinsic weakness of the pernicious anemia blood corpuscle. It is questionable whether blood destruction is as important a factor in producing the anemia of pernicious anemia as it is at present usually assumed to be.
Occupational allergic contact dermatitis: the big challenge
Authors: A. Bauer
Journal: British Journal of Dermatology (2014)

Journal Article Occupational allergic contact dermatitis: the big challenge Get access A. Bauer A. Bauer Department of Dermatology University Hospital Carl Gustav Carus Technical University Dresden Fetscherstr. 74 01307 Dresden Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 170, Issue 5, 1 May 2014, Pages 1010–1011, https://doi.org/10.1111/bjd.13018 Published: 01 May 2014
Atrial High Rate Episodes Detected by Pacemaker Diagnostics Predict Death and Stroke
Authors: Taya V. Glotzer, Anne S. Hellkamp, John Zimmerman, Michael O. Sweeney, Raymond Yee, Roger Marinchak, James Cook, Alexander Paraschos, John Love, Glauco Radoslovich, Kerry L. Lee, Gervasio A. Lamas
Journal: Circulation (2003)

Background— Some current pacing systems can automatically detect and record atrial tachyarrhythmias that may be asymptomatic. We prospectively studied a 312-patient (pt) subgroup of MOST (MOde Selection Trial), a 2010-patient, 6-year randomized trial of DDDR versus VVIR pacing in sinus node dysfunction (SND). The purpose of the study was to correlate atrial high rate events (AHREs) detected by pacemaker diagnostics with clinical outcomes. Methods and Results— Pacemakers were programmed to log an AHRE when the atrial rate was &gt;220 bpm for 10 consecutive beats. Analysis was confined to patients with at least 1 AHRE duration exceeding 5 minutes. The 312 patients were median age 74 years, 55% female, and 60% had a history of SVT. 160 of 312 (51.3%) patients enrolled had at least 1 AHRE &gt;5 minutes duration over median follow-up of 27 months. Cox proportional hazards analysis assessed the relationship of AHREs with clinical events, adjusting for prognostic variables and baseline covariates. The presence of any AHRE was an independent predictor of the following: total mortality (hazard ratio AHRE versus no AHRE and 95% confidence intervals=2.48 [1.25, 4.91], P =0.0092); death or nonfatal stroke (2.79 [1.51, 5.15], P =0.0011); and atrial fibrillation (5.93 [2.88, 12.2], P =0.0001). There was no significant effect of pacing mode on the presence or absence of AHREs. Conclusions— AHRE detected by pacemakers in patients with SND identify patients that are more than twice as likely to die or have a stroke, and 6 times as likely to develop atrial fibrillation as similar patients without AHRE.
<i>PIK3CA</i> Genotype and Treatment Decisions in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: David W. Cescon, Philippe L. Bedard
Journal: Journal of Clinical Oncology (2015)

Genotyping of patient tumors has been rapidly incorporated into both clinical trials and clinical practice over the last several years, with the goal of advancing personalized or precision cancer medicine. The crux of these efforts is to identify actionable alterations— genetic changes that can be used to guide individualized treatment. Dramatic advances in sequencing technologies and DNA isolation methods now enable multiplex hotspot mutation testing or targeted exome se
US Health Care: A Look Ahead to 2025
Authors: Eli Ginzberg
Journal: Annual Review of Public Health (1999)

The chapter begins with a reminder that forecasting changes in the health care sector a quarter to a third of a century in the future is likely to be a losing effort, based on past experience. It next considers changing organization and financing and questions that managed care and market competition will be the key forces introducing change. The author looks forward to the passage of universal health insurance coverage for essential care by early in the new century, with patients having to pay for more choice and more quality. The analysis next focuses on the physician supply and points to three challenges: how to moderate the numbers being trained; whether to reconsider the conventional wisdom of training more generalists; and how to support more resources for the National Health Service Corps to improve coverage in underserved areas. The author predicts the restructuring of acute care hospitals, with a marked reduction of in-patient beds, and that leading-edge research-oriented academic health centers should be able to remain out in front. There are also potential gains in health status from prevention and molecular medicine in a nation where chronic disease will dominate.
Transluminal angioplasty: correlation of morphologic and angiographic findings in an experimental model.
Authors: P C Block, K L Baughman, R C Pasternak, J T Fallon
Journal: Circulation (1980)

The morphologic consequences of transluminal angioplasty of stenotic atherosclerotic coronary arteries are unknown. This study describes the production of aortoiliac atherosclerosis in rabbits and reports the morphologic changes after transluminal angioplasty of stenotic arterial lesions. Atherosclerotic lesions were evaluated angiographically before and after transluminal angioplasty and were studied histologically and by electron microscopy after angioplasty. Moderatley stenotic aortic segments showed denudation of endothelial cells and deposition of a carpet of platelets enmeshed in fibrin. Medial and intimal compression were not seen. Intimal plaque disruption and splitting of atheromatous plaques were observed in more stenotic vessels where dilatation during angioplasty is relatively greater. Transluminal angioplasty, therefore, acutely causes desquamation of endothelial cells and superficial plaque elements, splitting of atheroma and subsequent deposition of platelets and fibrin in the area of angioplasty. This experimental model may be useful to evaluate the morphologic changes after angioplasty and might be used in further studies to determine the long-term pathophysiologic changes after transluminal angioplasty.
Inhibitory Activity of Clinical Thiazolidinedione Peroxisome Proliferator Activating Receptor-γ Ligands Toward Internal Mammary Artery, Radial Artery, and Saphenous Vein Smooth Muscle Cell Proliferation
Authors: Stephanie T. de Dios, Dennis Bruemmer, Rodney J. Dilley, Melanie E. Ivey, Garry L.R. Jennings, Ronald E. Law, Peter J. Little
Journal: Circulation (2003)

Background— The proliferation of vascular smooth muscle cells (VSMCs) is a known response to arterial injury that is an important part of the process of restenosis and atherosclerosis. People with diabetes have an increased risk of cardiovascular disease resulting from accelerated coronary atherosclerosis. The newest drugs for Type 2 diabetes are thiazolidinediones, which are insulin-sensitizing peroxisome proliferator activating receptor-γ (PPARγ) ligands. We investigated the antiproliferative effects of troglitazone, rosiglitazone, and pioglitazone on VSMCs derived from the three vascular beds used for coronary artery by-pass grafting: the internal mammary and radial artery and saphenous veins. Methods and Results— The three vessels yielded proliferating cells of slightly differing morphology. Inhibition of cell proliferation was assessed by cell counting and cell cycle studies by Western blotting for phosphorylated retinoblastoma protein. All three thiazolidinediones showed inhibitory potency toward cell proliferation with a potency troglitazone&gt;rosiglitazone≈pioglitazone, and this potency profile was maintained toward the growth factor and insulin-stimulated phosphorylation of the retinoblastoma protein, which controls cell cycle progression. Conclusion— The inhibitory potency of clinical thiazolidinediones toward different vascular sources is dependent on the individual thiazolidinedione and very little on the vascular source.
Non-uniform electrophysiological properties and electrotonic interaction in hypertrophied rat myocardium.
Authors: E C Keung, R S Aronson
Journal: Circulation Research (1981)

We studied the distribution and nature of the electrical changes associated with myocardial hypertrophy induced by renal hypertension in rats. Standard microelectrode techniques were used to study transmembrane action potentials recorded from endocardial, papillary muscle, and epicardial stimulation from hypertrophied (HBP) and normal (SHAM) hearts. We also determined the effects of stimulation frequency on the action potentials recorded from these preparations. To assess whether altered intercellular electrical connections contribute to the electrophysiological changes associated with hypertrophy, we analyzed the spatial steady state voltage decrement produced by passing intracellular constant current pulses and determined the effective input resistance (Rin) of endocardial HBP and SHAM preparations. Our results show that the action potential prolongation that accompanies hypertrophy is not uniform. Thus, the entire course of repolarization is prolonged in epicardial and papillary muscle fibers, but only the latter half of repolarization is prolonged in epicardial fibers. Endocardial action potentials is general, and HBP action potentials in particular, have a distinctive steep relation between duration and stimulation frequency which may be due to a difference in the rate dependence of a membrane conductance(s), although relatively greater accumulation of extracellular potassium or altered activity of the Na+-K+ pump cannot be excluded as contributing factors. In addition, the similarity in the profile of spatial voltage decrement and the values for Rin in HBP and SHAM preparations indicates that alterations in electrotonic coupling between cells are unlikely to account for the prolonged action potentials of hypertrophied myocardium.
Evaluation of a patient referral contact tracing programme for hepatitis B and C virus infection in drug injectors
Authors: D D Brewer, H Hagan
Journal: Eurosurveillance (2009)

Effective contact tracing for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection could enhance disease control, especially in populations with low HBV vaccination rates and high prevalence of untreated HCV infection. We evaluated a low-cost approach to HBV/HCV contact tracing in injection drug users (IDUs). Index cases (n=26) were IDUs who seroconverted to HBV and/or HCV during a prospective cohort study in Seattle. Interviewers elicited index cases' recent injection partners and administered recall cues and other techniques to boost recall. Index cases received vouchers for free hepatitis testing, which they were to give to locatable partners. Persons redeeming vouchers also received small monetary incentives. Most (26/40) seroconverters participated in the paid contact interviews. Index cases reported many partners (mean=17), and in the aggregate, index cases indicated they could refer more than one third of their elicited partners for testing. Overall, only 17 persons were ultimately referred and just eight of these were confirmed as partners sought for referral. The supplementary elicitation techniques, and especially the recall cues, increased reporting of injection partners substantially. The injection network constructed from reported partnerships was mostly connected and cyclic. Successful contact tracing in IDUs likely requires active involvement by public health staff to locate and notify exposed injection partners.