tbuckley/cabot-search huggingface dataset:
Cyclophosphamide Is Associated with Pulmonary Function and Survival Benefit in Patients with Scleroderma and Alveolitis
Authors: Barbara White, Wendy C. Moore, Fredrick M. Wigley, Hui Qing Xiao, Robert A. Wise
Journal: Annals of Internal Medicine (2000)

Background: Lung inflammation (alveolitis) may cause lung fibrosis in scleroderma. Objective: To determine whether cyclophosphamide treatment is associated with retention of lung function and improved survival in scleroderma patients with alveolitis. Design: Retrospective cohort study. Setting: Johns Hopkins and University of Maryland Scleroderma Center. Patients: 103 patients with scleroderma who had bronchoalveolar lavage or lung biopsy. Intervention: Cyclophosphamide therapy. Measurements: 1) Serial measurement of forced vital capacity [FVC] and carbon monoxide diffusing capacity and 2) survival. Results: During a median follow-up of 13 months after bronchoalveolar lavage or biopsy, patients with alveolitis who did not receive cyclophosphamide therapy experienced a decrease in FVC (mean difference, −0.28 L [95% CI, −0.41 to −0.16 L] and −7.1% of the predicted value [CI, −10.9% to −4.0%]). Carbon monoxide diffusing capacity also decreased in these patients (mean difference, −3.3 mmol · min − 1 · kPa − 1 [CI, −4.6 to −2.1 mmol · min − 1 ·kPa − 1] and −9.6% of the predicted value [CI, −16.7% to −2.4%]). During a median follow-up of 16 months, patients with alveolitis who received cyclophosphamide were more likely to have a good outcome (stabilization or improvement) in FVC (relative risk, 2.5 [CI, 1.5 to 4.1]) and diffusing capacity (relative risk, 1.5 [CI, 1.0 to 2.2]). These patients also had improved survival; the median survival rate was 89% (25th, 75th percentiles, 84%, 94%) compared with 71% (25th, 75th percentiles, 55%, 86%) in untreated patients (P = 0.01, log-rank test). Conclusions: The presence of lung inflammation identifies patients with scleroderma who are more likely to have worsening lung function. Lung function outcomes and survival are improved in patients with alveolitis who receive cyclophosphamide.
Abstract P6-11-03: Beyond the Second Line Chemotherapy in Metastatic Breast Cancer: When Stop the Treatment between Science and Conscience
Authors: G Bernardo, R Palumbo, G Poggi, A Bernardo, C Teragni, M Frascaroli, A Amatu, B Montagna, B Tagliaferri, F Sottotetti, D Albanese, MR. Strada
Journal: Cancer Research (2010)

Abstract Background: Women with metastatic breast cancer (MBC) are increasingly offered third line chemotherapy, but the usefulness of treatment beyond the second line remains a therapeutic challenge. The aim of this study was to determine which benefit could be brought by successive lines of chemotherapy (CT) in patients with MBC and to identify factors affecting outcome and survival. Patients and methods: This retrospective analysis included 980 women treated with CT for MBC at our Institution over a seven year period (September 1998-September 2006). With overall survival (OS) data updated at December 1, 2008, the median follow-up was 125 months (range 48-192), OS and time to treatment failure (TTF) were calculated according to the Kaplan-Meyer method for each CT line. Cox proportional hazards model was used to identify factors that could influence TTF and OS. Results: Median OS evaluated from day 1 of each CT line decreased with the line number from 34.8 months (980 patients, first line, range 4-208) to 22.6 months (838 patients, second line), 14.6 months (684 patients, third line), 12.4 months (302 patients, fourth line), 9.4 months (88 patients, fifth line), 8.2 months (45 patients, seven or more lines). Median TTF ranged from 9.2 months to 7.8 and 6.4 months for the first, second and third line, respectively, with no significant decrease observed beyond the third line (median 5.2 months, range 4.8-6.2). In univariate analysis factors positively linked to a longer duration of TTF for each CT line were positive hormonal receptor status, absence of liver metastasis, adjuvant CT exposure, response to CT for the metastatic disease; in the multivariate analysis the duration of TTF for each CT line was the only one factor with significant impact on survival benefit for subsequent treatments (P&amp;lt;0.001). Conclusions: Our results stress that CT beyond the first line may be beneficial in a significant subset of women treated for MBC. For patients responding to a given CT regimen and asking for further treatment after disease relapse, it appears useful to deliver subsequent active lines to get prolonged TTF and OS benefit. Patients who do not respond to the first two lines of CT should be considered for clinical trials or supportive care. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-03.
Genetically Modified Hematopoietic Stem Cell Transplantation for HIV-1–infected Patients: Can We Achieve a Cure?
Authors: Patrick Younan, John Kowalski, Hans-Peter Kiem
Journal: Molecular Therapy (2013)

The cure of a human immunodeficiency virus (HIV)-1-infected patient following allogeneic transplantation from a CCR5-null donor and potential cure of two patients transplanted with CCR5 wild-type hematopoietic stem cells (HSC) have provided renewed optimism that a potential alternative to conventional antiretroviral therapy (ART) is forthcoming. While allogeneic grafts have thus far suggested complete eradication of viral reservoirs, it has yet to be observed following autologous HSC transplantation. Development of curative autologous transplantation strategies would significantly increase the number of treatable patients, eliminating the need for matched donors and reducing the risks of adverse events. Recent studies suggest gene therapy may provide a mechanism for developing curative therapies. Expression of cellular/artificial restriction factors or disruption of CCR5 has been shown to limit viral replication and provide protection of genetically modified cells. However, significant obstacles remain with regards to the depletion of established viral reservoirs in an autologous transplantation setting devoid of the "allo-effect". Here, we discuss results from early-stage clinical trials and recent findings in animal models of gene modified HSC transplantation. Finally, we propose innovative combination therapies that may aid in the reduction and/or elimination of viral reservoirs in HIV-1-infected patients and promote the artificial development of a natural controller phenotype.
Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia
Authors: Stefan A Grathwohl, Roland E Kälin, Tristan Bolmont, Stefan Prokop, Georg Winkelmann, Stephan A Kaeser, Jörg Odenthal, Rebecca Radde, Therese Eldh, Sam Gandy, Adriano Aguzzi, Matthias Staufenbiel, Paul M Mathews, Hartwig Wolburg, Frank L Heppner, Mathias Jucker
Journal: Nature Neuroscience (2009)
Functional Mechanisms Underlying Tachycardia-Induced Sustained Atrial Fibrillation in a Chronic Dog Model
Authors: Rania Gaspo, Ralph F. Bosch, Mario Talajic, Stanley Nattel
Journal: Circulation (1997)

Rapid atrial activation causes electrical remodeling that promotes atrial fibrillation (AF), but underlying mechanisms are incompletely understood. We applied epicardial mapping to evaluate atrial electrophysiology and AF duration in dogs subjected to rapid atrial pacing (400/min).Dogs paced for 1 (P1, n=7), 7 (P7, n=13), or 42 (P42, n=7) days were compared with sham dogs (P0, n=13). Atrial pacing progressively increased AF duration. Atrial effective refractory period (ERP) and ERP accommodation to rate were significantly decreased by pacing, with near-maximal changes within 7 days. Atrial conduction velocity decreased more slowly, with maximum changes at 42 days, contributing to increases in AF duration after ERP stabilized. Stepwise multilinear regression indicated that both wavelength (P=.02) and duration of pacing (P=.0001) were independent determinants of changes in AF duration. Mean atrial fibrillation cycle length (AFCL) at 112 recording sites decreased with increased duration of rapid pacing (P<.001), and the SD of AFCL increased progressively (P<.0001), together accounting for 72% of the variance in AF duration. Increases in AFCL variability were due to regionally determined differences in AFCL changes caused by rapid pacing. The number of zones of reactivation per cycle of AF increased as AF became more sustained, consistent with multiple-wavelet reentry.Rapid atrial activation causes time-dependent decreases in ERP, conduction velocity, and wavelength, which, along with increased regional heterogeneity, provide a substrate for AF. The conduction abnormalities and increased regional heterogeneity previously noted in patients with AF may be a consequence, as well as a cause, of the tachyarrhythmia.
Gastrointestinal Imaging in Pediatrics
Authors: Jeremiah Kelleher
Journal: JAMA (1983)

Seven years after the appearance of<i>Gastrointestinal Radiology in Pediatrics</i>, Dr Franken has delivered the second edition. The new title,<i>Gastrointestinal Imaging in Pediatrics</i>, reflects both the changing practice of the radiologist and the expanded content of this textbook. This edition has 632 pages, compared with a previous 323. The list of authors has suffered even higher inflation—from two to 18, drawn from three continents. The price is a modest $75. The first chapter deals with techniques of examination and will be very helpful to those who examine children infrequently. Chapters 2 to 11 give a systematic account of the radiology of the gastrointestinal (GI) tract, including liver, pancreas, and spleen. There are separate and extensive chapters on angiography, computed tomography, nuclear medicine, and ultrasound. Each chapter concludes with an extensive list of references. This is a good textbook. It is a comprehensive text by leading experts in each field.
The Safe Administration of Anaesthetics: With Special Reference to Chloroform and Methylene: A Report of Six Hundred Cases
Authors: C. O'Neill
Journal: BMJ (1897)

IML JonA 1465 tact and resolution may be requisite in pressing for an inquiry into this important matter; indeed, some individuals seem to resent almost as a personal affront a hint that the sanitary arrangements of a house which they have made their abode can be otherwise than perfect.Latterly, I have seen a great many cases from India, more especially from certain parts of Bombay and Burmah, in which acute inflam- mation of the tympanum has gone on to perforation and discharge, and I have been unable to attribute this mischief to anything else than foulness of atmosphere from unhealthy surroundings.
Defibrillator failures. Causes of problems and recommendations for improvement. Defibrillator Working Group
Authors: R. O. Cummins
Journal: JAMA (1990)

The Defibrillator Working Group of the Food and Drug Administration reviewed data from the Medical Device Reporting System and a recent five-state survey, as well as information presented at two Food and Drug Administration-sponsored conferences. These data include 156 reports of defibrillator problems to the Emergency Care Research Institute Problem Reporting Network, 495 reports of device problems to the Medical Device Reporting System, 676 reports of "defibrillator failure" in the five-state survey, 594 inspections of in-service defibrillators, and site visits to 212 emergency care facilities. The Defibrillator Working Group concluded that the frequency of defibrillator failures during clinical use may be unacceptably high. While some failures are attributable to component malfunctions, evidence suggests that errors in operator use and errors in defibrillator care and maintenance account for a high proportion of defibrillator failures. Inadequate initial training and cursory continuing education increases the chances of operator errors at the moment when correct operation is needed most. Failure of operators to perform daily equipment checks leads to poor familiarity with the equipment and failure to identify component failures or damaged devices. Many defibrillators and batteries are kept in service beyond an expected useful life, given their level of clinical use. In smaller hospitals and emergency medical services systems periodic maintenance responsibilities are not always appropriately delegated between qualified engineering personnel and defibrillator operators, and some systems completely lack services from clinical engineers. The objectives of the Defibrillator Working Group are to make personnel who use defibrillators more aware of the potential for errors in operator performance and in periodic maintenance and to recommend improvements in training, maintenance, and defibrillator design. This article presents the initial observations and recommendations of the working group.
Drinking at the last chance saloon
Authors: F. Godlee
Journal: BMJ (2010)

Distinguished voices are lining up behind England’s chief medical officer Liam Donaldson in support of a minimum price for alcohol ( BMJ 2009;338:b1124, doi:10.1136/bmj.b1124). The BMA and the Royal College of Physicians have made a good case ( BMJ 2009;339:b2714, doi:10.1136/bmj.b2714 and BMJ 2010;340:c80, doi:10.1136/bmj.c80), and this week they are joined by the combined weight of the Faculty of Public Health and the Royal Society for Public Health (doi:10.1136/bmj.c342). These two bodies list a minimum price for alcohol among 12 policy changes that will save many lives and relieve pressure on the NHS. As the faculty’s president Alan Maryon-Davies says, in lean times such action is all the more essential. …
Extracorporeal shock wave lithotripsy: the first 50 patients treated in Britain.
Authors: J E Wickham, D R Webb, S R Payne, M J Kellet, G Watkinson, H N Whitfield
Journal: BMJ (1985)

Fifty patients have been treated for upper tract urinary calculi by extracorporeal shock wave lithotripsy (ESWL) at the Devonshire Hospital lithotripter centre since November 1984. The average stay for an inpatient was 3 X 7 days. All patients suffered minimal postoperative discomfort and nearly all resumed normal activity within one day after discharge. Complications requiring auxiliary procedures were few. The procedure was found to be safe, cost effective, extremely well received by patients, and superior to all other methods of removing renal stones. This study confirms that treatment by ESWL is a specialised urological procedure that requires operators who are also trained in open, percutaneous, and ureteroscopic surgery and with a back up of a radiological team skilled in percutaneous renal puncture.
Detection of specific IgE in isocyanate and phthalic anhydride exposed workers: comparison of RAST RIA, Immuno CAP System FEIA, and Magic Lite SQ
Authors: G. Mazur, A. Pethran
Journal: Allergy (1993)

Sera from 94 workers occupationally exposed to isocyanate were tested by RAST RIA, Immuno CAP FEIA, and Magic Lite SQ (ML) against the allergens HDI, MDI, TDI, and phthalic anhydride. Twenty sera showed increased levels of diisocyanate‐specific IgE antibodies, and five sera were phthalic anhydride positive. High total IgE titer was not correlated with positive specific IgE titer ( r = 0.47), showing that nonspecific IgE binding was low. The results of ML and CAP correlated well ( r = 0.91), but tended to be slightly higher than the results obtained with the RAST isotope test. CAP and RAST data also correlated significantly ( r = 0.90), but the correlation between ML and RAST data was lower ( r = 0.82). The results of the new in vitro tests, CAP and ML, showed good reproducibility (5% CV for CAP and 8% CV for ML). In summary, the CAP and ML methods were found to be appropriate for routine diagnosis of specific IgE antibodies against the allergens HDI, MDI, TDI, and phthalic anhydride.
Prevalence of Diabetes and Impaired Glucose Tolerance in Elderly Subjects and Their Association With Obesity and Family History of Diabete
Authors: Leena Mykkänen, Markku Laakso, Matti Uusitupa, Kalevi Pyörälä
Journal: Diabetes Care (1990)

The goal of this study was to investigate the prevalence of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) in elderly subjects and their association with obesity, central obesity, and a family history of diabetes. A representative population sample of 1300 subjects (471 men, 829 women) aged 65-74 yr participated in the study. The participation rate was 71%. The prevalence rates of previously and newly diagnosed NIDDM and IGT, based on a history of diabetes and an oral glucose tolerance test, were 8.7, 7.0, and 17.8% in men and 11.7, 7.1, and 19.1% in women. Thus, 33.8% of men and 37.9% of women had abnormal glucose tolerance according to World Health Organization criteria. Obesity (body mass index greater than or equal to 27 kg/m2 in men and greater than or equal to 25 kg/m2 in women) and central obesity (waist-hip ratio greater than or equal to 0.98 in men and greater than or equal to 0.89 in women) doubled the prevalence of IGT or NIDDM. The combination of obesity and a family history of diabetes was associated with a more marked increase in the prevalence of IGT or NIDDM in men than in women. Simultaneous presence of obesity, central obesity, and a family history of diabetes was associated with a threefold increase in the prevalence of IGT or NIDDM (65.4 vs. 24.1% in men, 52.8 vs. 19.6% in women, P less than 0.001). The major risk factors for NIDDM, e.g., obesity, central fat distribution, and a family history of diabetes, explained 10% of the variance in 2-h glucose values in multiple regression analysis. In conclusion, the prevalence of IGT and NIDDM was high in elderly subjects. Although obesity, central fat distribution, and a family history of diabetes were significantly associated with the increased prevalence of IGT or NIDDM, they explained only a minor proportion of the variance in 2-h glucose values.
Effect of Hormones on Maintenance of Hyperplastic Alveolar Nodules in Mammary Glands of Various Strains of Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Satyabrata Nandi
Journal: JNCI Journal of the National Cancer Institute (1961)

Uniparous or multiparous mice of strains C3H/Crgl, C3H/Crgl/2, RIII/DmCrgl, DBA/2NCrgl, A/Crgl, and A/Crgl/3, which differ in their susceptibility to mammary cancer, were hypophysectomized-ovariectomized-adrenalectomized and treated with adrenocortical or adrenocortical + adenohypophysial hormones for 15 days. Examination of untreated intact mice showed that hyperplastic alveolar nodules were present in the mammary glands of all strains. Most nodules regressed, if the hypophysectomized-ovariectomized-adrenalectomized mice were treated with deoxycorticosterone acetate (DCA) + corticosterone acetate (B) only. However, treatments with DCA + B + mammotropin and DCA + B + somatotropin were found to be equally effective in maintaining the hyperplastic nodules at a level of development similar to that of intact mice of comparable strains, and initiated lactation in some of them. There were no significant strain differences in the response of hyperplastic alveolar nodules to these two hormone combinations. It is suggested that, although the hormone requirements for nodule formation may differ in different strains, the requirements for maintenance appear to be the same, regardless of strain.
Lead Exposure Risk is Associated with Asthma in a Low-income Urban Hispanic Population: Results of the Communities Organized against Asthma and Lead (COAL) Project
Authors: A.M. Motosue, S. Petronella, J. Sullivan, S. Castillo, T. Garcia, M. Murillo, J.D. Calhoun, R. Chhickara, D. Bethel, J.B. Ward Jr.
Journal: Journal of Allergy and Clinical Immunology (2009)
Cardiac Metastasis in a Patient With a Bronchial Carcinoid
Authors: María José Calero Rueda, Gonzalo Aldamiz-Echevarría, Antonia Arjonilla López, Carlos Sánchez Almaraz, Aranzazu García Romero, Rosa Sánchez-Aquino, Jaime Fernández-Cuadrado, Isabel Díaz Buschmann
Journal: Circulation (2014)
Primary Prevention With Metoprolol in Patients With Hypertension
Authors: J. Staessen
Journal: JAMA (1988)

To the Editor.—  We read with interest the recent article by Wikstrand and coworkers. 1 These investigators employed the Gehan-Wilcoxon nonparametric test for survival analysis and found in male hypertensive patients with diastolic blood pressures ranging from 100 through 129 mm Hg that total ( P =.028) and cardiovascular ( P =.012) mortality were reduced by metoprolol therapy compared with treatment with a thiazide diuretic. The 95% confidence interval for the reduction in total mortality at median follow-up (4.16 years) ranged from - 68% to -17%. However, the 95% confidence limits for the differences between the two treatment groups in cardiovascular mortality at median followup and in both total and cardiovascular mortality at the end of the study were not published.  Using methods that were described previously 2 and the results published in Table 3 of the Metoprolol Atherosclerosis Prevention in Hypertensives Study, 1 we calculated these 95% confidence intervals. We confirmed that
Rheumatoid Arthritis and Jaundice
Authors: W. L. Peacock
Journal: BMJ (1938)

<h3>Summary</h3> Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell adhesion properties, supports HIO growth <i>in vitro</i> and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. Additionally, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted <i>in vivo</i>, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.
Peripheral Nociception Associated With Surgical Incision Elicits Remote Nonischemic Cardioprotection Via Neurogenic Activation of Protein Kinase C Signaling
Authors: W. Keith Jones, Guo-Chang Fan, Siyun Liao, Jun-Ming Zhang, Yang Wang, Neal L. Weintraub, Evangelia G. Kranias, Jo El Schultz, John Lorenz, Xiaoping Ren
Journal: Circulation (2009)

Although remote ischemic stimuli have been shown to elicit cardioprotection against ischemia/reperfusion injury, there is little known about the effects of nonischemic stimuli. We previously described a remote cardioprotective effect of nonischemic surgical trauma (abdominal incision) called remote preconditioning of trauma (RPCT). In the present study, we elucidate mechanisms underlying this phenomenon.We used a murine model of myocardial infarction to evaluate ischemia/reperfusion injury, and either abdominal surgical incision, or application of topical capsaicin, to elicit cardioprotection. We show that the cardioprotective effect of RPCT is initiated by skin nociception, and requires neurogenic signaling involving spinal nerves and activation of cardiac sensory and sympathetic nerves. Our results demonstrate bradykinin-dependent activation and repression, respectively, of PKCepsilon and PKCdelta in myocardium after RPCT, and we show involvement of the K(ATP) channels in cardioprotection. Finally, we show that topical application of capsaicin, which selectively activates C sensory fibers in the skin, mimics the cardioprotective effect of RPCT against myocardial infarction.Nontraumatic nociceptive preconditioning represents a novel therapeutic strategy for cardioprotection with great potential clinical utility.