tbuckley/cabot-search huggingface dataset:
Commissioning complementary medicine
Authors: I. Smith
Journal: BMJ (1995)

The opportunities presented to commissioning health authorities to decide what health care to purchase for local people has also provided an opportunity to rethink old prejudices. The old prejudices against complementary medicine are being rethought for several reasons. Firstly, many commissioning authorities and fundholding general practitioners are either commissioning or providing complementary medicine as part of routine contracting.1 Financially, this is marginal activity, costing typically less than pounds sterling20000 a year out of an average authority budget of pounds sterling200m. Also some complementary medicines, such as acupuncture and homoeopathy, have been part of normal NHS activity for many years and this has blurred the margins between conventional and complementary medicine. Secondly, the medical profession has relaxed its attitude toward complementary medicine over the past decade.2 Thirdly, both main political parties support the development of …
Death Among Patients Hospitalized With Pneumonia
Authors: Mihaela S. Stefan, Randa Jaber, Peter K. Lindenauer, Jane L. Garb, Janet Fitzgerald, Michael B. Rothberg
Journal: JAMA Internal Medicine (2015)

The Affordable Care Act established the Value-Based Purchasing Program, launched in 2013, which uses risk-standardized mortality rates as a benchmark to penalize or reward hospitals.1 The risk-standardized mortality rate is calculated using administrative data and includes patients with life-threatening illnesses for whom pneumonia may be the last insult in the setting of terminal illness. Moreover preferences for limiting the use of or withdrawing life-sustaining therapy are considered only for patients already enrolled in hospice on the day of admission. Therefore, risk-standardized mortality rates measure the outcome of care but not necessarily the appropriateness and value of care.2

We sought to determine the proportion of patients identified with pneumonia by the Centers for Medicare & Medicaid Services risk-standardized mortality measures for whom pneumonia was a major contributor to death and to describe the intensity of care and patient preference for life-sustaining therapies.
Abstract 5438: Resistance to β1 integrin inhibition in HER2 amplified cancers is mediated by HER3
Authors: Catherine C. Park, Dhara Amin, Hui Zhang, Mark Moasser
Journal: Cancer Research (2014)

Abstract Our previous work focused on investigating β1 integrin as a target for BC, alone and with radiation therapy. It is well recognized that there is significant cross talk between the EGFR family of receptors and β1 integrin signaling, and a relative resistance of HER2+ BC to β1 integrin inhibitory agents. In 2006, we published our findings that β1 integrin inhibition enhanced the effect of trastuzumab in HER2+ BC. Subsequently, others and we reported that β1 integrin inhibition enhanced the cytostatic effect of multiple HER2-targeted therapies in HER2+ BC. However, the nature of cross talk between β1 integrins and HER2, and the role of β1 integrin in HER2+BC resistance remains unknown. In addition, HER2+BCs have higher rates of local recurrence after radiotherapy, consistent with previous work showing relative radioresistance in HER2+BC. The most potent mitogenic HER2 signaling in HER2+BC occurs upon heterodimerization with HER3. We hypothesized that HER3 could mediate significant resistance to β1 integrin targeting in HER2+BC. To test this, we correlated β1 integrin and HER3 expression levels in SKBR3 cells over several time points using WB. Inhibitions of β1 integrin activity or shRNA knockdown of HER3 lead to upregulation of HER3 and β1 integrin, respectively. To test whether HER3 knockdown enhanced β1 integrin inhibition, we estimated proliferation by quantitating Ki-67 expression in SKBR3 cells in response to treatment. β1 integrin inhibition lead to a ∼50% reduction in Ki-67 positive cells (48%-22%), which was further enhanced by 50% with HER3 knockdown (12%), p&amp;lt;0.05. In addition, HER3 knockdown enhanced the cytostatic effect of ionizing radiation (IR) by ∼50% (32% to 14%), p&amp;lt;0.05. Enhanced cytostasis was correlated with a significant down modulation of p-HER2 and p-473 Akt on WB. In conclusion, our data indicate that HER3 plays a role in mediating resistance to β1 integrin inhibition in HER2+BC. Further mechanistic and in vivo validation are on going. Citation Format: Catherine C. Park, Dhara Amin, Hui Zhang, Mark Moasser. Resistance to β1 integrin inhibition in HER2 amplified cancers is mediated by HER3. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5438. doi:10.1158/1538-7445.AM2014-5438
Interaction of heterozygous β<sup>o</sup>‐thalassemia with single functional α‐globin gene
Authors: Renzo Galanello, Elisabetta Paglietti, Maria A. Melis, Maria G. Crobu, Maria Addis, Paolo Moi, Antonio Cao
Journal: American Journal of Hematology (1988)

Abstract In this study, we analyzed the phenotypic manifestations resulting from the interaction of heterozygous β o ‐thalassemia(β o ‐39 nonsense mutation) with the functional loss of three α‐globin structural genes in six subjects, of whom four had the [‐αl–] α‐globin genotype and two the [–/αThα] α‐globin genotype. The β‐thalassemia defect was in all cases the nonsense mutation at codon 39. The nondeletion α‐thalassemia α th was the initiation codon mutation (AUG→GUG) of the α‐2 gene. In all these subjects hypochromia and microcytosis were more marked than in βα ‐thalassemia heterozygotes with a full complement of four α‐globin genes. All but one had moderate anemia. The α:β globin chain synthesis ratios were consistently decreased. No cases had Hb H on electrophoresis. Subjects with [–/αThα] α‐globin genotype had more severe thalassemia‐like manifestations than those with [–/‐α] α‐globin genotype.
Impaired Maximal Exercise Performance with Hypertensive Cardiovascular Disease
Authors: HEE ONG WONG, IRWIN S. KASSER, ROBERT A. BRUCE, Gladys Pettet, Verona Hofer
Journal: Circulation (1969)

Responses to a multistage treadmill test of maximal exercise were studied in 61 hypertensive patients: 13 had uncomplicated hypertension; 15 had associated retinopathy; 22 had left ventricular hypertrophy; and 11 also had coronary heart disease. Because of significant differences with aging normally, and differences in ages of these subgroups, responses were compared with those of normotensive persons matched for age and sex. With only elevated blood pressure there was no impairment of exercise performance and no increase in S-T segment depression. With ventricular hypertrophy and particularly with retinopathy, maximal exercise duration was shortened. Prevalence of postexertional myocardial ischemia, manifested by S-T segment depression, was increased threefold in those with hypertrophy of the left ventricle. Even greater impairment of exercise duration, maximal heart rate, and systolic pressure was observed in patients with coronary heart disease and hypertension. Prevalence of S-T segment depression was sevenfold greater. This ECG manifestation of myocardial ischemia may represent either an augmented contractile force or a significantly restricted coronary blood supply to limit myocardial perfusion. Differences in duration of exercise and circulatory responses, particularly the product of maximal heart rate and maximal systolic pressure/100, indicate these variations in pathophysiological mechanisms.
Patients with cystic fibrosis have inducible IL-17+IL-22+ memory cells in lung draining lymph nodes
Authors: Yvonne R. Chan, Kong Chen, Steven R. Duncan, Kira L. Lathrop, Joseph D. Latoche, Alison J. Logar, Derek A. Pociask, Brendon J. Wahlberg, Prabir Ray, Anuradha Ray, Joseph M. Pilewski, Jay K. Kolls
Journal: Journal of Allergy and Clinical Immunology (2012)
Mechanics of the Single Left Ventricle
Authors: Mark A. Fogel, Paul M. Weinberg, Krishanu B. Gupta, Jack Rychik, Anne Hubbard, Eric A. Hoffman, John Haselgrove
Journal: Circulation (1998)

Background —Left ventricular (LV) effects on right ventricular (RV) function are well known. Less is understood about the effect of the RV on systemic LV mechanics. To determine this interaction, we compared systemic LVs with and without an RV mechanically coupled to them. Methods and Results —MR myocardial tagging was used to examine 18 subjects with systemic LVs: 10 with functional single LVs (SLV) and 8 normal subjects (NL). Tracking the systolic motion of the intersecting stripes were used to determine regional twist and radial motion. Finite strain analysis was applied to derive principal strains at the atrioventricular valve (AVV) and apical short-axis levels and in 4 anatomic wall regions. Similar E 1 (circumferential shortening) strain and heterogeneity of strain were noted between SLV and NL except in the septal wall. At the septal wall, NL displayed greater absolute strain (AVV=−0.16±0.02, apex=−0.17±0.02) and less heterogeneity of strain than SLV (AVV=−0.12±0.02, apex=−0.13±0.02). Similar E 2 (wall thickening) strain and heterogeneity of strain were also noted between SLV and NL except again at the septal wall. At the septal wall, SLV displayed greater absolute E 2 strain (AVV=0.17±0.08, apex=0.19±0.09) and less heterogeneity of strain than NL (AVV=0.07±0.07, apex=0.05±0.05). SLV twisted significantly less counterclockwise than NL in 6 of 8 wall regions and actually twisted clockwise at the AVV lateral wall. Although there was no significant difference between groups in radial wall motion, the septal and inferior walls of SLV demonstrated significantly less radial motion compared with other SLV walls. Conclusions —A major influence of the RV on systemic LV strain and radial motion occurs in the septal wall, whereas absence of the RV causes marked differences in LV twist. These findings may yield clues to the long-term functioning of the SLV and be useful in determining strategies for RV augmentation of LV function.
Policy of AMA Journals Regarding Release of Information to the Public
Authors: George D. Lundberg
Journal: JAMA (1991)

Because of recent concerns (<i>New York Times</i>. November 16, 1990, and December 2,1990;<i>Chicago Tribune</i>. November 18, 1990) about the delay between the generation of clinically useful information for treatment of patients and the publication of this information in peer-reviewed journals,<sup>1,2</sup>we thought it would be a good idea to make explicit the policy we follow for the 10 journals that are published by the American Medical Association (AMA). The public is interested in health information, and the public news media try to provide it as quickly as possible. Peer-reviewed, primary source medical journals, however, consider original articles only if they have not been published previously. Thus, a conflict sometimes exists between the news media and editors of medical journals who prefer to disseminate complete medical information to physicians after validation through peer review. All concerned want medical information to be as accurate as possible. Medical editors rely on rigorous peer review to evaluate such accuracy prior to accepting papers, and physicians rely on journal publication to provide full information they can assess and explain to patients.
"Squelch sign" in detection of small herniae.
Authors: W G Everett
Journal: BMJ (1978)

<h3>Introduction</h3> Effective implementation of standard precautions specific to COVID-19 is a challenge for hospitals within the existing constraints of time and resources. <h3>Aim</h3> To rapidly design and operationalise personal protective equipment (PPE) donning and doffing areas required for a COVID-19 care facility. <h3>Methods</h3> Literature review was done to identify all issues pertaining to donning and doffing in terms of Donabedian’s structure, process and outcome. Training on donning and doffing was given to hospital staff. Donning and doffing mock drills were held. 5S was used as a tool to set up donning and doffing areas. Instances of donning and doffing were observed for protocol deviations and errors. Plan–do–study–act cycles were conducted every alternate day for 4 weeks. The initiative was reported using Standards for QUality Improvement Reporting Excellence (SQUIRE) guidelines. <h3>Results</h3> Best practices in donning and doffing were described. Our study recommends a minimum area of 16 m<sup>2</sup> each for donning and doffing rooms. Verbally assisted doffing was found most useful than visual prompts. <h3>Discussion</h3> Challenges included sustaining the structure and process of donning and doffing, varied supplies of PPE which altered sequencing of donning and/or doffing, and training non-healthcare workers such as plumbers, electricians and drivers who were required during emergencies in the facility. <h3>Conclusion</h3> Our study used evidence-based literature and quality improvement (QI) tools to design and operationalise donning and doffing areas with focus on people, task and environment. Our QI will enable healthcare facilities to rapidly prototype donning and doffing areas in a systematic way.
T3 Measuring eosinophil kinetics in humanS
Authors: N. Farahi, A. M. Condliffe, N. R. Singh, S. Heard, R. P. Simmonds, C. K. Solanki, K. Solanki, K. K. Balan, A. M. Peters, E. R. Chilvers
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Eosinophils are major cellular effectors of allergic inflammation and represent an important therapeutic target in asthma. While much is understood about the generation and activation of eosinophils, little is known about their intravascular kinetics and physiological fate. The purpose of this study was to image sites of eosinophil distribution and measure eosinophil kinetics in healthy individuals using autologous 111-Indium-labelled eosinophils. <h3>Methods</h3> To determine “gold standard” kinetics of minimally-manipulated eosinophils<b>,</b> mixed leucocytes were isolated from the blood of healthy volunteers, labelled with 111-Indium-tropolonate and re-injected. Blood was sampled 0.75–72 h post-injection. Neutrophils and eosinophils were isolated in parallel, and cell-associated radioactivity was measured. To image sites of eosinophil margination/uptake eosinophils were purified using plasma-Percoll gradients and anti-CD16 immunomagnetic beads, labelled with 111-Indium-tropolonate and re-injected. The distribution of eosinophils was recorded by γ camera dynamic imaging (0–40 min) followed by static imaging up to 72 h. <h3>Results</h3> Using minimally manipulated granulocytes we found that the 45min neutrophil recovery was 57±10% (n=7) and the intravascular lifespan was 10.3±0.1 h, in agreement with previous studies. By contrast, the 45min recovery of eosinophils was 15±2% (n=7) and eosinophil lifespan was 25.2±3.8 h. Moreover, eosinophils appeared to re-circulate at ∼4 h and 9 h before monoexponential removal. Using 111-Indium-eosinophils and γ camera imaging, we demonstrated initial retention of cells in the lungs, clearing to baseline by 40 min, with some early accumulation in the liver and progressive accumulation in the spleen (n=3). Simultaneous blood sampling showed that the 45 min recovery and intravascular lifespan of purified labelled eosinophils were 11±2% and 29.3±2.1 h, respectively, comparable to minimally manipulated cells. Purified cells also exhibited recirculation at ∼6 h and 12 h. Of note, the disappearance of eosinophils from the liver at 6 h and 9 h coincided with their re-appearance in circulating blood, suggesting the liver as a possible site of transient eosinophil sequestration. <h3>Conclusions</h3> This work provides the first in vivo measurements of eosinophil kinetics in healthy volunteers. Our data suggest that 111-In-labelled-eosinophils can be used to monitor the organ distribution and fate of eosinophils non-invasively. This technique may have an important role in assessing the therapeutic effects of eosinophil-targeted drugs.
Prophylaxis of Asiatic Cholera
Authors: H. Maccormac
Journal: BMJ (1873)

India, where so many circumstances combine to favour its occurrence ?The answer to this question I must leave to others who have had larger Indian experience than myself; and we must only hope that, now that more attention is being shown to the analysis of drinking-water in India, under the auspices of Dr. Macnamara and others, and that special inquiries as to the nature and spread of cholera are being systematically carried out by Dr.
Prevalence and etiology of altered liver tests: A population-based survey in a Mediterranean town
Authors: Gaspare Maria Pendino, Andrea Mariano, Pasquale Surace, Carmelo Antonio Caserta, Maria Teresa Fiorillo, Angela Amante, Stefania Bruno, Carmelo Mangano, Irene Polito, Fulvia Amato, Rodolfo Cotichini, Tommaso Stroffolini, Alfonso Mele
Journal: Hepatology (2005)

Serum biochemical liver tests (LTs) (ALT, AST, GGT) and platelet counts are often used to screen for chronic liver disease. Population-based data on abnormal LTs in Mediterranean areas are lacking. The prevalence and etiology of abnormal LTs were assessed from 2002 to 2003 in a 1 in 5 systematic random sample of the general population who were 12 years of age or older in Cittanova, a southern Italian town with 10,600 inhabitants. LTs, indices of metabolism, and markers of HBV and HCV infection were assayed and alcohol intake was recorded in the selected population. In virus-free individuals with abnormal LTs, LTs were retested, and upper abdominal echography and tests for other causes of liver damage were undertaken. Among the 1,645 individuals screened, the prevalence of anti-HCV was 6.5%; the prevalence was particularly high in individuals over 50 years of age. The corresponding prevalence for HBsAg was 0.8%. The overall prevalence of individuals with abnormal LTs was 12.7% (95% CI: 11.1-14.3). The probable cause of abnormal LTs was excessive alcohol in 45.6%, HCV in 18.6%, HBV in 1%, alcohol plus HCV and/or HBV in 8.8%, and rare diseases in 2%. In 24% of individuals with abnormal LTs, the probable cause was nonalcoholic fatty liver disease (NAFLD); in this subgroup, increased body weight, hypercholesterolemia, and hyperglycemia were common, and 63.3% of them had a bright liver at echography. In conclusion, in southern Italy, a Mediterranean area where dietary habits are different from those in industrialized areas, one eighth of the general population has abnormal LTs suggestive of possible liver damage; NAFLD appears to be emerging as a potentially important etiology of this presumed liver injury. (HEPATOLOGY 2005;41:1151–1159.)
Immunization against Lyme Disease — An Important First Step
Authors: Roy T. Steigbigel, Jorge L. Benach
Journal: New England Journal of Medicine (1998)

Lyme disease is an inflammatory disorder that can involve the skin and the musculoskeletal, neurologic, and cardiovascular systems.1 The etiologic agent, Borrelia burgdorferi, was isolated from tick vectors in 19822 and subsequently from patients in 1983.3,4 Lyme disease is the most common vector-borne disease in the United States, with 16,461 cases reported to the Centers for Disease Control and Prevention in 1996.5 Although cases have been reported in 45 states, they are clustered in the mid-Atlantic, Northeast, and North Central regions. The prevalence of Lyme disease is affected by the proportions of infected small-mammal reservoirs, tick vectors, and their . . .
SPECTRUM AND PREVALENCE OF CARDIAC RYANODINE RECEPTOR (RYR2) AND KIR2.1 (KCNJ2) MUTATIONS IN PATIENTS REFERRED FOR FAMILION&amp;reg; CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA (CPVT) GENETIC TESTING
Authors: Thomas E. Callis, Janet L. Carr, Lisa Susswein, Guido D. Pollevick, Michael Ackerman, Benjamin S. Salisbury
Journal: Journal of the American College of Cardiology (2012)
Focal Adhesions
Authors: Lewis H. Romer, Konstantin G. Birukov, Joe G.N. Garcia
Journal: Circulation Research (2006)

The vascular wall contains intimal endothelium and medial smooth muscle that act as contiguous tissues with tight spatial and functional coordination in response to tonic and episodic input from the bloodstream and the surrounding parenchyma. Focal adhesions are molecular bridges between the intracellular and extracellular spaces that integrate a variety of environmental stimuli and mediate 2-way crosstalk between the extracellular matrix and the cytoskeleton. Focal adhesion components are targets for biochemical and mechanical stimuli that evoke crucial developmental and injury response mechanisms including cell growth, movement, and differentiation, and tailoring of the extracellular microenvironment. Focal adhesions provide the vascular wall constituents with flexible and specific tools for exchanging cues in a complex system. The molecular mechanisms that underlie these vital communications are detailed in this review with the goal of defining future targets for vascular tissue engineering and for the therapeutic modulation of disordered vascular growth, inflammation, thrombosis, and angiogenesis.
85. Development of Zinc Finger Nucleases for Therapeutic Gene Correction of Sickle Cell Anemia
Authors: Jeffrey C. Miller, Fyodor D. Urnov, Ya-li Lee, Jeremy Rock, Tyler Sorba, Sarah Patterson, Philip D. Gregory, Michael C. Holmes, Edward J. Rebar
Journal: Molecular Therapy (2005)

Top of pageAbstract
We have developed an efficient strategy for introducing precise sequence changes into the human genome, and have initiated studies to apply our methods to the treatment of human disease. Our approach relies on our capacity to design Zinc Finger Protein Nucleases (ZFNs) to bind and cleave virtually any chosen location in the genome. In the first step, a double-stranded break is introduced within the targeted locus using a pair of designed ZFNs that function as a heterodimer. Next, a homologous donor DNA molecule is provided as a recombination substrate to direct precise alterations in the sequence flanking the break site. Recently it was demonstrated that this method can be used to modify an endogenous gene sequence with very high efficiency (>15% of all target sequences)1.

We have now begun developing this approach for the treatment of monogenic diseases. In the present application, ZFNs have been developed to target the |[beta]|-globin gene sequence at the precise location of the mutation causing sickle cell anemia. Development proceeded in several stages. First, a panel of candidate ZFNs was designed and tested for the ability to bind DNA in vitro. The ZFN pair with the highest affinity was then shown to efficiently cleave a DNA fragment corresponding to the |[beta]|-globin locus at the chosen target site. Importantly, the lead ZFN dimer also discriminated well against the corresponding sequence from the highly sequence-related globin paralogs. Next, the binding properties of the lead pair were further improved via site directed mutagenesis and the expansion of the DNA-binding domain of one of the ZFNs from four to six fingers, increasing the DNA recognition sequence from 12 to 18 bp. Finally, the resultant lead pair was tested in cells to determine its ability to cleave the globin target sequence in a chromosomal context. In this assay, the target sequence is embedded within a defective GFP reporter gene that is integrated into the genome of 293 cells. Cleavage of the target and subsequent repair of the GFP gene can be monitored by recovery of green fluorescence, and we observed efficient GFP conversion in this system. These experiments suggest that the current lead pair may be suitable for development of a therapeutic gene correction approach to sickle cell anemia, and we have initiated studies to test the ability of these ZFPs to mediate gene correction at the endogenous |[beta]|-globin locus.