tbuckley/cabot-search huggingface dataset:
GPs are handed sweeping powers in major shake up of NHS
Authors: J. Wise
Journal: BMJ (2010)

The NHS in England is to undergo a radical reorganisation, with GPs commissioning most services and the abolition of primary care trusts and strategic health authorities.

The government’s white paper contains far reaching proposals that devolve power from central government to patients and doctors. Reaction to the proposals has been mixed, with one concern being whether GPs will be given enough support to take on their new expanded role. Another worry is that such large scale change is risky at a time when huge efficiency savings have to be made.

A key plank of the white paper is that all general practices must join a consortium that will commission the majority of care for their patients. It is anticipated that GP consortiums will hold around 80% of the total NHS budget. The white paper states that the new model is “neither a recreation of GP fundholding nor a complete rejection of practice-based commissioning.”

There will be no fixed size for the commissioning consortiums, although the white paper says that they must be big enough to manage financial risk and allow for accurate allocations. The aim is for a shadow system of consortiums to be in place in 2011-12, with primary care trusts supporting practices during the transition process. GP consortiums will take on responsibility for commissioning in 2012-13 and will take full responsibility from April 2013. At this date all 152 primary care trusts will be abolished.

An independent and accountable NHS Commissioning Board will be established, which will hold the consortiums to account for their performance and quality. It will also allocate NHS resources to the consortiums, set commissioning guidelines, and commission dentistry, community pharmacy, primary ophthalmic, and maternity services. This will pave the way for the abolition of the 10 strategic health authorities in 2012-13.

Launching the white …
High prevalence of diabetes in an urban population in south India.
Authors: A. Ramachandran, M. V. Jali, V. Mohan, C. Snehalatha, M. Viswanathan
Journal: BMJ (1988)

An urban population in a township in south India was screened for diabetes with an oral glucose tolerance test, every fifth person aged 20 and over registered at the local iron ore company9s hospital being screened. Of 678 people (346 men and 332 women) who were tested, 34 (5%; 20 men and 14 women) had diabetes and 14 (2%; 8 men and 7 women) had impaired glucose tolerance. Thirteen subjects were already known to be diabetic. Diabetes was present in 21% (37/179) of people aged over 40. The peak prevalence (41%; 7/17) was in the group aged 55-64. A family history of diabetes was present in 16 of the 34 subjects with diabetes and nine of the 15 with impaired glucose tolerance. Diabetes was significantly related to obesity in women but not in men (57% (8/14) v 5% (1/20)). The plasma glucose concentration two hours after glucose loading was correlated to body mass index, age, and income in both sexes. The prevalence of diabetes was significantly higher in subjects whose income was above the mean. When the overall prevalence of diabetes was adjusted to the age distribution of the Indians living in Southall, London, and in Fiji it increased to 10% and 9%, respectively. The prevalence of diabetes is high among urban Indians and is comparable with the high prevalence seen in migrant Indian populations.
Collaboration Needed for HIV Vaccine Success
Authors: Rebecca Voelker
Journal: JAMA (1997)

A MUCH STRONGER public-private partnership is needed if a safe, effective vaccine against the human immunodeficiency virus (HIV) is going to be developed, says a new report entitled<i>Industry Investment in HIV Vaccine Research</i>. The AIDS Vaccine Advocacy Coalition (AVAC) in San Francisco, Calif, which released the report on World AIDS Day, says working relationships between government and industry have improved in recent years, but many deficits remain. In fact, the report's authors call government leadership the "key ingredient" needed to expedite the creation of a successful vaccine. "We were surprised to learn that, in most cases, government is the engine that drives industry and that industry research depends on government financing, government leadership, and government support," said Chris Collins, MPP, an author of the report and policy specialist at the Center for AIDS Prevention Studies at the University of California at San Francisco. <h3>Baltimore Appointment Hailed</h3> About a week
Noninvasive Quantification of Coronary Blood Flow Reserve in Humans Using Myocardial Contrast Echocardiography
Authors: Kevin Wei, Michael Ragosta, Jerrel Thorpe, Matthew Coggins, Sally Moos, Sanjiv Kaul
Journal: Circulation (2001)

Background —We hypothesized that coronary blood flow (CBF) reserve could be quantified noninvasively in humans using myocardial contrast echocardiography (MCE). Methods and Results —Eleven patients with normal epicardial coronary arteries (group I) and 19 with single-vessel coronary stenosis (group II) underwent quantitative coronary angiography, MCE, and CBF velocity measurements at rest and during intravenous adenosine infusion. In group I patients, MCE-derived myocardial blood flow (MBF) velocity reserve (2.4±0.08) was similar to CBF velocity reserve using a Doppler flow wire (2.4±1.1). Patients with a single risk factor had a significantly higher MBF reserve (3.0±0.89) than those with ≥2 risk factors (1.7±0.22). In group II patients, significant differences were found in MBF velocity reserve in patients with mild (&lt;50%), moderate (50% to 75%), or severe (&gt;75%) stenoses (2.2±0.40, 1.6±0.65, and 0.55±0.19, respectively; P =0.005). A linear relation was found between flow velocity reserve determined using the 2 methods ( r =0.76, P &lt;0.001), and a curvilinear relation was noted between the percent coronary stenosis measured using quantitative coronary angiography and velocity reserve using both methods. Conclusions —CBF reserve can be measured in humans using MCE. This method may allow the noninvasive assessment of coronary stenosis severity and the detection of microvascular dysfunction.
Hepatoma Metastatic to Rib
Authors: W. L. Shuffett
Journal: JAMA (1971)

To the Editor.—  The article by Reichback et al ( 213: 2078, 1970) discussed unusual osseous metastases from malignant hepatoma. The authors emphasized the bizarre nature of hepatoma metastases and reported two cases which presented with osseous spread as the initial manifestation. One of these lesions was a pulsatile mass in the right temporal area. The following case report describes another unusual presentation from an osseous metastasis of hepatoma.  Report of a Case.—  A 76-year-old white man presented at the University of Kentucky Medical Center with a chief complaint of pain in the right upper quadrant, nausea and vomiting, and fever of two days duration. He had a several-year history of fatty food intolerance and vague pain in the abdomen. His temperature was 101 F. Physical examination revealed marked tenderness in the right upper quadrant without evidence of a mass. Bowel sounds were decreased and a liver rub was heard over
Physiological and psychological correlates of success in track and field athletes.
Authors: T. R. Thomas, C. J. Zebas, M. S. Bahrke, J. Araujo, G. L. Etheridge
Journal: British Journal of Sports Medicine (1983)

Twenty-four collegiate distance runners and 20 power athletes (sprinters and jumpers) of various success levels were tested on a number of physiological and psychological parameters. Multiple regression analysis indicated that physiological factors could explain over 81% of the variance related to successful distance running while physiological and psychological factors could explain over 80% of the of the variance related to successful sprinting and jumping. Body weight, fibre type, low density lipoprotein-cholesterol, and hamstring strength were significant singular correlates to successful distance running. Year in school, percent body fat, quadriceps strength, and leg muscle balance were significant single correlates to successful sprinting and jumping performance.
At the Crossroads of Myocardial Signaling
Authors: W. Glen Pyle, R. John Solaro
Journal: Circulation Research (2004)

Understanding the molecular interactions among components of cardiac Z-discs and their role in signaling has become pivotal in explaining long- and short-term regulation of cardiac function. In striated muscle, the ends of the thin filaments from opposing sarcomeres overlap and are cross-linked by an elaborate array of proteins to form a highly ordered, yet dynamic network that is the Z-disc. We review here a current picture of the function and structure of the Z-disc of mammalian cardiac myocytes. We emphasize provocative findings that advance new theories about the place of cardiac Z-discs in myocardial intra- and intercellular signaling in myocardial physiology and pathology. Relatively new approaches, especially yeast two-hybrid screens, immunoprecipitation, and pull down assays, as well as immunohistochemical analysis have significantly altered previous views of the protein content of the Z-disc. These studies have generally defined domain structure and binding partners for Z-disc proteins, but the functional significance of the binding network and of the domains in cardiac cell biology remains an unfolding story. Yet, even at the present level of understanding, perceptions of potential functions of the Z-disc proteins are expanding greatly and leading to new and exciting experimental approaches toward mechanistic understanding. The theme of the following discussion of these Z-disc proteins centers on their potential to function not only as a physical anchor for myofilament and cytoskeletal proteins, but also as a pivot for reception, transduction, and transmission of mechanical and biochemical signals.
A study of a female with congenital sideroblastic anemia
Authors: Yutaka Manabe, Shiro Seto, Kenshi Furusho, Yosuke Aoki
Journal: American Journal of Hematology (1982)

Abstract A female infant with congenital refractory sideroblastic anemia is described. A market reduction of δ‐aminolevulinic acid (ALA) synthetase activity of erythroblasts was noticed with and without treatment of pyridoxal phosphate. Mitochondrial neutral protease activity of erythroblasts, which inactivates specifically the apo form of ALA synthetase, was normal and the sensitivity of apo form of ALA synthetase to the neutral protease was also normal. It was speculated that the reduction of ALA synthetase activity is not due to the high speed of destruction, but rather due to the impairment in production of ALA synthetase, which could explain the unresponsiveness to pyridoxine therapy in this case.
Short stature and its treatment.
Authors: A S Mason
Journal: BMJ (1972)

The axiom that diagnosis must precede treatment holds true for the management of short stature. What matters is the current rate of growth and the potential for further growth; it is essential to measure accurately the rate of gain in height and the radio logical bone age. Early detection of subnormal rate of growth can lead to prevention of dwarfism, but a dwarf with epiphyses closed is beyond remedy. A child's rate of gain in height is determined by genetic factors that require a benign internal environment for their full expression. No form of therapy can alter a genetically determined height velocity; treatment is possible if an adverse internal environment can be corrected. Smith1 gave an excellent account of the various forms of dwarfism, including the many eponymous genetic syndromes. The genetic short stature of atypical Turner's syndrome may not be recognized unless the karyotype is known from chromosomal studies. A more common difficulty in diagnosis is the normal slow-growing short child of short parents; the normality is obvious only if the child's height is corrected for parental height, using the data of Tanner et al.2 Any prolonged illness creates an adverse environment that slows the rate of gain of height. In the same way cyanotic congenital heart disease, chronic hepatic or renal failure, and uncontrolled diabetes mellitus stunt growth. Deficient food intake or absorption are more easily rectified causes of subnormal rate of gain of height. The dietary intake, both in quantity and quality, must be discovered. Steatorrhoea may present as short stature with minimal symptoms referable to the gut. The curious phenomenon of low height velocity due to emotional deprivation3 is difficult to separate from the nutritional stunting that may affect such unfortunate children. Obviously successful treatment of short stature depends on identifying and removing these adverse environmental conditions. Endocrine causes of subnormal height velocity are not common. Primary thyroid failure severely limits statural growth and may not be immediately apparent. Adequate tests of thyroid function are always required in assessing growth failure. It is also difficult to distinguish primary from secondary failure of the thyroid due to pituitary lesions. Pituitary function is modi fied by primary thyroid failure and the secretion of growth hormone is diminished. Therefore, it is not possible to obtain an accurate measure of the pituitary's capacity to secrete growth hormone unless the level of circulating thyroid hormone is normal. That glucocorticoid excess can seriously diminish height velocity is well known from the study of Cushing's
Oral Contraceptives and Hypertension
Authors: D. F. Horrobin, I. J. Lloyd, P. G. Burstyn
Journal: BMJ (1970)

There is a diversity of opinion upon the status of the haematologist.It should, how- ever, be clear that the bulk of laboratory investigations are performed by technicians, whose proficiency at fulfilling routine inves- tigations is far superior to most medical graduates.If the haematologist is to contri- bute more than gratuitous observations of anisocytosis, with a signature to give them authority if not meaning, then he needs the incentive of knowing he has a real job to perform.It is absurd to limit his function to that of an adviser sitting by a desk piled high with journals as the source of his authority.This authority may best come from experience of clinical medicine, labora- tory work, responsibility for treatment, and follow-up.If any one of these components
Predictive Biomarkers to Anti-VEGF Therapy: Progress toward an Elusive Goal
Authors: Rekha Gyanchandani, Seungwon Kim
Journal: Clinical Cancer Research (2013)

The search for reliable biomarkers predictive of response to anti-VEGF therapy has been elusive. VEGF-A, the therapeutic target of bevacizumab, is an intuitive candidate as a predictive biomarker to bevacizumab-based anticancer therapy. However, there remains much controversy in the use of VEGF-A as a predictor of response to bevacizumab.
Abstract 3240: The Wnt secretion factor Evi/Wls/Gpr177 promotes glioma tumorigenesis
Authors: Iris Augustin, Violaine Goidts, Angelika Bongers, Grainne Kerr, Bernhard Radlwimmer, Christian Hartmann, Christel Herold-Mende, Andreas von Deimling, Guido Reifenberg, Michael Boutros
Journal: Cancer Research (2012)

Abstract Malignant astrocytomas are highly aggressive brain tumors with poor prognosis. Despite multimodal therapy, including surgical resection followed by combined radio- and chemotherapy, the median survival of glioblastoma patients has remained as low as 12-14 months throughout the past decade. While a number of structural genomic changes and dysregulation of signaling pathways in gliomas have been described, the identification of biomarkers and druggable targets remains an important task for novel diagnostic and therapeutic approaches. Recent evidence supports the involvement of canonical and non-canonical Wnt signaling in glioma development and malignant progression. Here, we show that the Wnt-specific secretory protein Evi (also known as GPR177/Wntless/Sprinter) is overexpressed in astrocytic gliomas. Evi/Wls is a core Wnt signaling component and a specific regulator of pan-Wnt protein secretion, affecting both canonical and non-canonical signaling. We demonstrate that its depletion in glioma and glioma-derived stem-like cells led to decreased cell proliferation and apoptosis. Furthermore, Evi/Wls silencing in glioma cells reduced cell migration and the capacity to form tumors in vivo. We further show that Evi/Wls overexpression is sufficient to promote downstream Wnt signaling. Taken together, our study identifies Evi/Wls as an essential regulator of glioma tumorigenesis, identifying a pathway- specific protein trafficking factor as an oncogene and offering novel therapeutic options to interfere with the aberrant regulation of growth factors at the site of production. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3240. doi:1538-7445.AM2012-3240
S44 Lung clearance index (LCI) and FEV1 correlate equally with treatment burden as measured by cystic fibrosis questionnaire-revised (CFQ-R)
Authors: K. O'Neill, J. M. Bradley, M. Tunney, J. S. Elborn
Journal: Thorax (2011)

<h3>Introduction</h3> LCI derived from multiple breath washout (MBW), measures the elimination of an inert marker gas during tidal breathing and is a sensitive measure of ventilation inhomogeneity in CF. LCI is more sensitive than FEV<sub>1</sub> and FEF<sub>25−75</sub> in detecting airways abnormalities and does not require a forced manoeuvre. The CFQ-R is a validated patient reported outcome used to assess health related quality of life (HRQoL) and patient perception of symptoms. There is a need to better understand the relationship between LCI, HRQoL and symptoms. <h3>Objective</h3> To investigate the relationship between LCI, FEV<sub>1</sub> % pred, HRQoL and symptoms as measured by the CFQ-R. <h3>Methods</h3> These data are part of a larger study investigating the role of LCI as a tool to monitor lung function longitudinally. Patients were recruited from the adult and paediatric CF centres in Belfast Health and Social Care Trust. Inclusion criteria: clinical diagnosis of CF; clinically stable (exacerbation free=4 weeks); informed consent. Age appropriate versions of the CFQ-R were used (patients &gt;14 years, children aged 12 and 13, children aged 6–11). A parent questionnaire was completed in addition where appropriate (for children aged 6–13). The instrument yielded a score of 0–100 for each domain, with higher numbers indicating better function on various domains. Participants completed three MBW tests, using 0.2% sulphur hexafluoride and a modified Innocor device. LCI was reported as the mean of at least 2 acceptable tests. Spirometry was performed to ATS/ERS standards. <h3>Results</h3> Data were collected for 21 patients (15M:6F), age range 6–51 yrs, mean (SD) 26.4 (13.7). Mean (SD) FEV<sub>1</sub> % pred was 77.1 (16.3). Mean (SD) LCI was 9.4 (2.5) (normal &lt;7.5). LCI correlated negatively with FEV<sub>1</sub>% pred (r=−0.62 p=0.003). The domain of treatment burden was significantly correlated with LCI (r=−0.67 p=0.001) and FEV<sub>1</sub>% pred (r=0.69 p=0.001). However no correlation was observed with respiratory symptoms or any other domain of the CFQ-R. <h3>Conclusion</h3> Patients with a greater treatment burden are more likely to have more severe lung disease. The severity of CF lung disease as determined by FEV<sub>1</sub>% pred and LCI correlate equally with treatment burden. This further validates LCI as a useful measure of lung function.
A NOTE ON RECURRENT LARYNGEAL PARALYSIS
Authors: W. G. Howarth
Journal: BMJ (1924)

MAAcTT 1 rt.o1z2A1 RECURRENT LARYNGEAL PARALYSIS.[r M .PC,BrJIA CsSC 465In these days, when lay criticism of, and intrusion into, delicate medical findings is apt to be pronounced and over- whelming, it may be well to be reinforced, as regards the critical public duty of small-pox diagnosis, with clinical methods which have stood the test of experience; which are simple to remember, simple and quick to apply, simple in interpretation, yielding results which are correct, easily recorded, convincing, and permanent for subsequent reference by means of observations, every repetition of which materially fortifies and heightens a sound and correct judgement.
Analysis of T helper and antigen-presenting cell functions in cord blood and peripheral blood leukocytes from healthy children of different ages.
Authors: M Clerici, L DePalma, E Roilides, R Baker, G M Shearer
Journal: Journal of Clinical Investigation (1993)

The development of antigen-specific functional T lymphocyte immunity in infants and children is an area of immunology that needs elucidation. Leukocytes from cord blood (CBL) and from PBL of children of different ages who were in the hospital for minor surgical procedures were compared with PBL from healthy adults for their ability to generate T helper cell (Th) responses assessed by in vitro proliferation and IL-2 production after stimulation with: influenza A virus (FLU); tetanus toxoid (TET); adult allogeneic PBL that were either undepleted (ALLO) or depleted of adherent antigen presenting cells (ALLONW); and PHA. CBL generated Th responses to ALLONW, ALLO, and PHA, but not to FLU or TET. PBL from infants between 6 and 13 mo of age responded to ALLO and PHA; none responded to FLU or ALLONW, and two of four responded weakly to TET. PBL from children between 13 and 26 mo of age responded to all stimuli except FLU, to which only one child responded marginally. PBL from children older than 36 mo responded to all stimuli at levels comparable to those of PBL from adults. The use of undepleted and adherent cell-depleted CBL and PBL from children of different ages as allogeneic stimulators of responses generated by PBL from adults indicated that the antigen presenting function of CBL and PBL from children 13 mo or older are sufficiently developed to present alloantigen, whereas PBL from children younger than 13 mo are not. Therefore, our results indicate that age-dependent differences exist in both T helper and antigen-presenting functions of CBL and PBL from children of different ages. Surprisingly, CBL appear to be more efficient in antigen-presenting function than PBL from children younger than 13 mo. These findings are important for establishing developmental parameters of T helper cell immunity relevant for pediatric infection and transplantation in infants and children.
QUANTITATIVE ASPECTS OF THE SPONTANEOUS ELUTION OF INFLUENZA VIRUS FROM RED CELLS
Authors: Bernard Sagik, Theodore Puck, Seymour Levine
Journal: The Journal of Experimental Medicine (1954)

Each chick and human red cell contains approximately 300 sites capable of attaching influenza virus particles. These correspond to an area representing approximately 2 per cent of the red cell surface. Although the rate of attachment of PR8 to red cells is not diffusion-limited, when calculated on the basis of the total cell area, it does approach the theoretical maximum for interaction between the virus and the fraction of the cell area known to contain attachment sites. It is demonstrated that the virus attachment can initiate a spreading disturbance on the red cell membrane which extends over an area far exceeding that covered by the attached virus and which leads to the destruction of receptor sites. This process does not involve cyclic virus attachment, elution from the cell, and reattachment to another site. Practically all the receptor sites on a cell are destroyed before any virus is liberated into the medium. The spontaneous elution of virus from red cells within 24 hours at 37 degrees C. requires a threshold value of at least 3 and less than 5 virus particles per cell. Parallelisms between the spontaneous elution reaction and the phenomenon of lysis-from-without in the bacteriophage system are demonstrated.