tbuckley/cabot-search huggingface dataset:
Cost Control — Time to Get Serious
Authors: Daniel Callahan
Journal: New England Journal of Medicine (2009)

Although everyone seems to agree that controlling health care costs is no less critical a need than improving access to health care, the evidence suggests that cost control is not being seriously confronted. The pertinent committees in Congress, as well as key government agencies, are still flitting around the edge of tough proposals, evading the enormous difficulties of managing costs.Consider the first shot across the bow of serious cost reform, conveyed in an April 29, 2009, report of the Senate Finance Committee. Comparative-effectiveness research, it said, is a fine idea, but whatever "entity" carries it out "should be prohibited . . .
Fruits, Vegetables and Cancer Dimensions
Authors: A. I. Holleb
Journal: CA A Cancer Journal for Clinicians (1975)

O â€oe¿ The protruding cauliflower-like lesion is of medium size.â€•According to the United States Department of Agriculture, olives vary in size from â€oe¿ subpetiteâ€• to â€oe¿ superco lossalâ€•; the dimensions of grapes, oranges and grapefruits depend on sea son, geographic origin and other factors; peas (presumably the black-eyed type as well) show considerable differences in the number required to make up one quart; eggs come in small, medium, large and extra-large, and from a wide variety of birds.Inexplicably, one phys ical examination report described a mass as the size of a â€oe¿ hardboiled egg.â€•The above suggests a deterioration in the art of tumor description.It seems ap propriate, therefore, to register a plea for recording as accurately as possible the dimensions of tumors in centimeters.Attention to detail is important not only for maintaining high medical standards, but also for better clinical staging of cancer, evaluating prognosis when tumor size is pertinent, determining response to treatment and for adequate follow-up by others less experienced with agricultural products.Once and for all, let us eschew fruits and vegetables in reports of tumor size.
Efferent sympathetic and vagal innervation of the canine right ventricle.
Authors: M Ito, D P Zipes
Journal: Circulation (1994)

BACKGROUND The functional pathways of efferent sympathetic and vagal innervation to the right ventricle (RV) might be important in a variety of disease states that involve the RV wall. The purpose of this study was to investigate those pathways. METHODS AND RESULTS We determined the effects of phenol and endocardial radiofrequency ablation applied to the RV anterolateral wall and outflow tract on effective refractory period (EPR) shortening during bilateral ansae subclaviae stimulation and ERP lengthening during bilateral vagal stimulation. We found that efferent sympathetic axons to the RV are located in the superficial subepicardium and that lateral sites receive sympathetic innervation predominantly from the lateral margin of the RV near the AV groove. Medial sites close to the left anterior descending coronary artery (LAD) receive sympathetic innervation from both the right lateral atrioventricular (AV) groove and regions near the LAD. At the RV outflow tract, some sympathetic fibers are located intramurally. Efferent vagal fibers are located at the RV surface within 10 mm of the right lateral AV groove; they penetrate intramurally and reach to the medial sites of the RV anterior wall. Other vagal fibers originate near the LAD and are intramural. Vagal fibers to the RV outflow tract are located intramurally either from the lateral side (close to the right coronary artery) or medial side (close to the LAD). CONCLUSIONS Efferent vagal and sympathetic innervation of the right ventricle resembles that of the left ventricle. A major difference is that efferent sympathetic fibers to the right ventricular outflow tract are located not only in the subepicardium but in the subendocardium as well.
Abstract A22: Combined simvastatin and anti-IGF-1R therapy of prostate cancer cells in co-culture with bone
Authors: Annika Nordstrand, Marie Lundholm, Andreas Larsson, Ulf Lerner, Anders Widmark, Pernilla Wikström.
Journal: Cancer Research (2012)

Abstract Prostate cancer frequently metastasizes to the bone. Bone metastases show weak responses to the conventional therapies given today, and patients with metastases cannot be cured. Bone matrix is rich in stored growth factors, with IGF-1 being one of the most abundant. IGF-1 acts as a survival factor for tumor cells and we speculate that bone-derived IGF-1 weakens the effects of therapies aimed to target bone metastases and, furthermore, that effects of apoptosis inducing therapies could be enhanced if given in combination with therapies inhibiting the IGF-1 receptor (IGF-1R). Simvastatin inhibits the mevalonate pathway and have been found to induce apoptosis of prostate cancer cells. The aims of this study were to confirm stimulating effects of bone-derived IGF-1 on prostate cancer cell growth and to test if IGF-1R inhibition could enhance simvastatin therapy effects on prostate cancer cells in a bone environment. Prostate cancer PC-3 and 22Rv1 cells were co-cultured with mice calvarias for 72 h and showed significantly increased cell numbers compared to when cultured alone. A phospho-RTK array confirmed activation of the IGF-1R on PC-3 and 22Rv1 cells by calvaria-conditioned media, and neutralization of bone-derived IGF-1 abolished the calvaria-induced increase of PC-3 cell growth. Treatments of PC-3 and 22Rv1 cells with simvastatin and the IGF-1R inhibitor NVP-AEW541 reduced tumor cell numbers and cell viability, and induced apoptosis, as assessed by flow cytometry analysis of Annexin-V. Combined s imvastatin and NVP-AEW541 treatments resulted in enhanced growth inhibitory effects compared to either therapy given alone. Expression analysis by RT-PCR and Western blot indicated that the therapeutic effects of simvastatin involved down-regulation of the IGF-1R in PC-3 cells and of the constitutively active androgen receptor AR-V7 variant in 22Rv1 cells. In conclusion, we believe that a combination of IGF-1R inhibition with simvastatin, and possibly other apoptosis inducing therapies, can provide novel and improved treatment regimes for prostate cancer bone metastases. Citation Format: Annika Nordstrand, Marie Lundholm, Andreas Larsson, Ulf Lerner,Anders Widmark, Pernilla Wikström. Combined simvastatin and anti-IGF-1R therapy of prostate cancer cells in co-culture with bone [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A22.
Obstetric importance, diagnosis, and management of fetal tachycardias.
Authors: D. J. Maxwell, D. C. Crawford, P. V. Curry, M. J. Tynan, L. D. Allan
Journal: BMJ (1988)

During 1980-7, 23 pregnancies of 22-38 weeks9 duration were investigated for fetal tachycardia. Twelve were cases of supraventricular tachycardia, eight of atrial flutter, and three cases in which the rhythm varied between supraventricular tachycardia and atrial flutter. In 11 cases the fetus had developed non-immune fetal hydrops before referral; 12 cases were non-hydropic at referral but one of this group of fetuses became hydropic during treatment. No relation was found between the rate or type of arrhythmia and the presence or absence of intrauterine heart failure. One non-hydropic infant was delivered electively prematurely. Maternal antiarrhythmic treatment was instituted in the remaining 22 cases. Conversion of the arrhythmia was achieved with digoxin alone in five cases and with a combination of digoxin and verapamil in nine. Control of the arrhythmia was achieved in seven of the 10 non-hydropic fetuses, and all were delivered at term with no deaths. Of the 12 hydropic fetuses, control was achieved in seven. Only three of the hydropic fetuses were delivered close to term. There were two deaths, both in the hydropic group. Of the whole group, five neonates suffered severe complications of prematurity. In this series the main benefit of treatment appeared to be in prolonging gestation of those hydropic fetuses in which conversion was achieved.
Extracellular Signal-Related Kinase Positively Regulates Ataxia Telangiectasia Mutated, Homologous Recombination Repair, and the DNA Damage Response
Authors: Sarah E. Golding, Elizabeth Rosenberg, Steven Neill, Paul Dent, Lawrence F. Povirk, Kristoffer Valerie
Journal: Cancer Research (2007)

Abstract The accurate joining of DNA double-strand breaks by homologous recombination repair (HRR) is critical to the long-term survival of the cell. The three major mitogen-activated protein (MAP) kinase (MAPK) signaling pathways, extracellular signal-regulated kinase (ERK), p38, and c-Jun-NH2-kinase (JNK), regulate cell growth, survival, and apoptosis. To determine the role of MAPK signaling in HRR, we used a human in vivo I-SceI–based repair system. First, we verified that this repair platform is amenable to pharmacologic manipulation and show that the ataxia telangiectasia mutated (ATM) kinase is critical for HRR. The ATM-specific inhibitor KU-55933 compromised HRR up to 90% in growth-arrested cells, whereas this effect was less pronounced in cycling cells. Then, using well-characterized MAPK small-molecule inhibitors, we show that ERK1/2 and JNK signaling are important positive regulators of HRR in growth-arrested cells. On the other hand, inhibition of the p38 MAPK pathway generated an almost 2-fold stimulation of HRR. When ERK1/2 signaling was stimulated by oncogenic RAF-1, an ∼2-fold increase in HRR was observed. KU-55933 partly blocked radiation-induced ERK1/2 phosphorylation, suggesting that ATM regulates ERK1/2 signaling. Furthermore, inhibition of MAP/ERK kinase (MEK)/ERK signaling resulted in severely reduced levels of phosphorylated (S1981) ATM foci but not γ-H2AX foci, and suppressed ATM phosphorylation levels &amp;gt;85% throughout the cell cycle. Collectively, these results show that MAPK signaling positively and negatively regulates HRR in human cells. More specifically, ATM-dependent signaling through the RAF/MEK/ERK pathway is critical for efficient HRR and for radiation-induced ATM activation, suggestive of a regulatory feedback loop between ERK and ATM. [Cancer Res 2007;67(3):1046–53]
PRELIMINARY REPORT OF AN EXPERIENCE IN THE GROUP PSYCHOTHERAPY OF SCHIZOPHRENICS
Authors: JOSEPH ABRAHAMS
Journal: American Journal of Psychiatry (1948)

This experience may be discussed in the following terms: 1. It demonstrates that schizophrenic individuals can be led into psychotherapeutically effective relationships with each other in a group setting, through the exercise of a special type of group leadership. 2. The establishment of a therapeutic atmosphere in this type of group is marked by the gradual spread of a way of behaving or group mores accepted by all the members, of helpfulness, acceptance, awareness, and a desire for understanding of the other patients' problems, and, through that, to understanding of their own. 3. This atmosphere is established through the leadership of the doctor working through example and by the adoption by the patient, in his relationships with other patients, of the doctor's way of relating to him. The doctor needs to be as aware as possible of the dynamics of the group as a whole and of members to each other and to the group. He needs to be ready when necessary to protect the individual patient and the group from the impact of the intense emotion associated with the deep-seated disturbance of the psychotic. 4. The ability of one schizophrenic to understand another's defenses against anxiety results, in this therapeutic atmosphere, in the bringing to awareness of the meaning of their interpersonal relationships and the uncovering of earlier experiences associated with the patient's anxieties. 5. The therapeutic process resulted at first in an increase in hostile, depressed, and manic-like reactions, but, within a few months, there was established a gradual amelioration of the patients' social isolation, boredom, recrimination, and combativeness, and the substitution of a more cooperative atmosphere. The individuals also showed their improvement by an increasing ability to tolerate reality without recourse to psychotic defenses.
New and unproved medical devices
Authors: A. S. Kesselheim, J. Avorn
Journal: BMJ (2013)

Paediatric tracheostomy is most commonly performed in children on the paediatric intensive care unit (PICU) to facilitate long-term ventilation. We sought to identify trends in UK tracheostomy practice in PICUs. Data were analysed from 250 261 admissions, including 4409 children tracheostomised between 2003 and 2017. The incidence of tracheostomy in 2017 was approximately half that in 2003 (incidence rate ratio=0.48, 95% CI 0.40 to 0.57). The percentage of patients tracheostomised during a PICU admission, as a proportion of all admissions, was 2.44% (n=319) in 2003 and reduced to 0.97% (n=180) in 2017. Nevertheless, we identified great variability in practice between different PICUs with tracheostomy rates between 0.0% and 4.0% of all admissions. Risk-adjusted PICU mortality was comparable between tracheostomised children and all admissions to PICU.
The Systemic Inflammatory Response in the Development of Ventilator-Associated Pneumonia
Authors: MARC J. M. BONTEN, ALBERT H. M. FROON, CARLO A. GAILLARD, JAN WILLEM M. GREVE, PETER W. de LEEUW, MARJOLEIN DRENT, ELLEN E. STOBBERINGH, WIM A. BUURMAN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Ventilator-associated pneumonia (VAP) is the most frequent occurring infection among mechanically ventilated patients. The clinical presentation of VAP ranges from relatively benign to a severe illness with septic shock. The influence of VAP on patient outcome has not been elucidated and its effects on the inflammatory response of the host are unknown. In a case-control study, the systemic inflammatory response was investigated in patients developing VAP as compared with control patients matched on duration of mechanical ventilation and underlying diseases. Patients developing VAP (n = 42) were matched to a single control (without VAP), who was matched on seven variables. VAP was diagnosed with bronchoscopic techniques. The inflammatory response, reflected by circulating levels of interleukin-6 (IL-6) and interleukin-8 (IL-8), was determined on the day of diagnosis (or day of matching for controls), 4 and 2 d before diagnosis, and 2 d after diagnosis. The development of VAP was not associated with an increase in circulating levels of IL-6 or IL-8. Among patients in which VAP was associated with a clinical presentation of severe sepsis or septic shock (n = 10), IL-6 and IL-8 levels increased and were higher than in the corresponding controls. Moreover, 60% of cases with severe sepsis or septic shock died as compared with 20% of their matched controls (p = 0.06). Mortality rates were similar in patients with uncomplicated VAP and their matched controls (25% and 34%, respectively). High circulating levels of IL-6 and IL-8 were associated with higher mortality rates. The clinical picture of VAP can be subdivided into different types, ranging from uncomplicated to an infection associated with severe sepsis or septic shock, elevated circulating levels of IL-6 and IL-8, and an increased mortality rate.
Absence of left ventricular dysfunction during acute chagasic myocarditis in the rhesus monkey.
Authors: J A Lima, A Szarfman, S D Lima, R J Adams, R J Russell, A Cheever, T Trischmann, J L Weiss
Journal: Circulation (1986)

Recent studies suggest that intracellular Trypanosoma cruzi invasion with release of intracellular myocardial antigens during T. cruzi infection is crucial to the pathogenesis of chronic chagasic myocarditis. However, in areas endemic for Chagas' disease, the incidence of clinical acute chagasic myocarditis has been reported to be low among infected individuals, while the incidence of chronic chagasic myocarditis is relatively high. Thus, either acute chagasic myocarditis rarely complicates T. cruzi infection and is not important to the pathogenesis of chronic chagasic myocarditis, or acute chagasic myocarditis rarely impairs left ventricular function and therefore causes no symptoms. To investigate this question we innoculated T. cruzi from a human patient with Chagas' disease into the subconjuntivae of six rhesus monkeys (7.5 X 10(3) parasites each). Parasitemia was monitored and weekly two-dimensional echocardiograms (for determination of end-diastolic and fractional change in area, EDA and FCA) were obtained to quantify global left ventricular function for 10 weeks. Regional left ventricular function was assessed by visual analysis of two-dimensional echocardiograms. Extent of acute myocarditis was established at autopsy. All monkeys had the Romaña sign and detectable parasitemia in the second week. Parasitemia rose in all by the ninth week (mean = 1.8 X 10(5) parasites/ml); four monkeys lost weight (mean = -12%), three died, and three were killed. Two-dimensional echocardiographic EDA and FCA remained unchanged from control to the last study within 12 hr of death (EDA = 2.6 +/- 0.9 to 2.7 +/- 1.0 cm2, FCA = 80 +/- 6.8 to 74 +/- 7.6%, NS). Furthermore, regional left ventricular function remained unchanged throughout the period of study.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of Genetic Loci Associated With Helicobacter pylori Serologic Status
Authors: Julia Mayerle, Caroline M. den Hoed, Claudia Schurmann, Lisette Stolk, Georg Homuth, Marjolein J. Peters, Lisette G. Capelle, Kathrin Zimmermann, Fernando Rivadeneira, Sybille Gruska, Henry Völzke, Annemarie C. de Vries, Uwe Völker, Alexander Teumer, Joyce B. J. van Meurs, Ivo Steinmetz, Matthias Nauck, Florian Ernst, Frank-Ulrich Weiss, Albert Hofman, Martin Zenker, Heyo K. Kroemer, Holger Prokisch, Andre G. Uitterlinden, Markus M. Lerch, Ernst J. Kuipers
Journal: JAMA (2013)

Helicobacter pylori is specifically adapted to colonize the mucus layer covering the gastric mucosa, with little invasion of the gastric glands. 1,2It is the major cause
The Homeless and the Public Household
Authors: Paul Elliot Starr
Journal: New England Journal of Medicine (1998)

Robert Frost once described home as “the place where, when you have to go there, /They have to take you in.”1 This is precisely what the homeless lack: not only a home of their own but also a claim on anyone else — kin, community, or government — to take them in and give them a home. Chronic illness, physical as well as mental, commonly accompanies homelessness and may have contributed to it in the first place. Often, however, it is only when the homeless become acutely ill that they are able to make a large claim on resources from . . .
Quantitative analysis of the high-frequency components of the terminal portion of the body surface QRS in normal subjects and in patients with ventricular tachycardia.
Authors: P Denes, P Santarelli, R G Hauser, E F Uretz
Journal: Circulation (1983)

Quantitative analysis of the high-frequency components of the terminal portion of the surface QRS was performed in 42 normal subjects (group 1, ages 18-67 years, mean +/- SEM 34.7 +/- 2.2 years) and in 12 patients with symptomatic, sustained ventricular tachycardia (VT) (group 2, ages 48-76 years, mean 59 +/- 2.3 years). Signal averaging and high-pass, bidirectional digital filtering were used for analysis. The total duration of the QRS, the duration of the low-amplitude signals (less than 40 microV) in the terminal portion of the QRS and the amplitude of the signals in the last 40 and 50 msec of the QRS were measured at filter settings of 25 and 40 Hz. Reproducibility of the measurements was tested in 15 normal subjects by comparing results obtained from two consecutive recordings. Significant differences were found between normal subjects and VT patients for all four indexes at both 25- and 40-Hz filters. Specific values for each of the indexes were identified at the 40-Hz filtering, which could separate normal subjects from VT patients (20 microV for the amplitude of last 40 msec; 30 microV for the amplitude of last 50 msec; 120 msec for the total duration; and 39 msec for the low-amplitude signal of the filtered QRS). Using these values for the four indexes, respectively, 90%, 98%, 100% and 90% of the normal subjects and 83%, 83%, 58% and 83% for the VT group were correctly classified. The results show that the high-frequency analysis of the signal-averaged body surface QRS is a reliable, reproducible, noninvasive method for distinguishing patients with VT from normal subjects.
Complications in Surgery
Authors: Daniel J. Kacey
Journal: JAMA (2011)

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EPIDEMIC CEREBROSPINAL MENINGITIS
Authors: ARTHUR H. PARMELEE
Journal: JAMA (1913)

The report which follows is based on a series of 230 cases treated at the Kansas City Ganeral Hospital during the epidemic from Jan. 1 to June 1, 1912. The statistics are compiled from the observations and bedside notes made by the attending physicians and interns of the hospital. I believe the data to be accurate, and the whole report a reliable picture of the epidemic in its clinical features.
The log rank test
Authors: P. Sedgwick
Journal: BMJ (2010)

The previous two statistical questions described survival (time to event) data.1 2 The example used was a randomised controlled trial that evaluated the effectiveness of an integrated care programme compared with usual care in facilitating the return to work of patients with chronic low back pain.3 The integrated care programme was a combined patient and workplace directed intervention. 

Trial participants were adults aged between 18 and 65 years who had experienced low back pain for more than 12 weeks, were in paid work, and were absent or partially absent from work. The primary outcome was duration of time off work—that is, from randomisation until a fully sustained return to work. 

Participants were followed for 12 months. The survival (time to event) data for the two treatment groups were compared statistically using the log …
The Role of Mast Cells in the Pathophysiology of Asthma
Authors: Judith Black
Journal: New England Journal of Medicine (2002)

The mast cell has long been considered to be of paramount importance in the pathophysiology of asthma. Its key role in driving the IgE-mediated allergic reaction and thus the early asthmatic response is well documented. In addition, there is evidence that it responds to non-IgE stimuli in the airway — for example, changes in the osmotic cellular environment associated with such challenges as exercise, hypertonicity, and hypotonicity. The array of mediators released from the activated mast cell is diverse, including prostaglandins; leukotrienes; cytokines, such as interleukins 1, 2, 4, 10, and 13; growth factors, such as platelet-derived growth factor and . . .