tbuckley/cabot-search huggingface dataset:
Trends in paediatric medical admissions.
Authors: J. O. Forfar
Journal: BMJ (1989)

direct a patient who still needs nursing to a private nursing home it may well be breaking the law.The circulars state that arrangements for dis- charge to other than the patient's home must be made in good time and be acceptable to the patient and, where appropriate, the patient's carers.Where a person moves from hospital to a private nursing home it should be made clear to him or her in writing before the transfer whether or not the health authority will pay the fees under a con- tractual arrangement.No NHS patients should be placed in private nursing homes or residential care homes against their wishes if it means that they or their relatives will be personally responsible for the charges.Up and down Britain cash starved hospitals, desperately trying to cope with an aging population, are discharging patients to nursing homes.They are probably breaking the law by not pro- viding for the sick elderly, and it is an interesting legal point whether the hospital or the consultant could be held responsible for paying the family's expenditure.
Local Advocacy for the Medically Indigent
Authors: Vicki Mayster
Journal: JAMA (1990)

Access to health care for the medically indigent has emerged as a major policy issue throughout the United States. Because no national health program ensures entitlement to basic services, practitioners and patients must cope with barriers to access on the local level. We report several separate but integrated strategies that a community-based coalition has used to achieve improvements in indigent care within a single county. Research strategies have involved short-term investigations of barriers to needed services so that local awareness of the problem would increase rapidly. Political strategies have attempted to improve the county government's administrative procedures and financial support of services for the poor, to modify the practices of local health care institutions, and to influence state and national policies that affect local conditions. Legal strategies have involved the participation of attorneys who represent clients unable to receive care and who could initiate litigation as appropriate. Each of these strategies contains weaknesses as well as strengths. Although such advocacy efforts do not achieve a coherent system that guarantees access, they can substantially improve the availability of local services.The authors report on the research, political, and legal strategies used by a community-based coalition to improve indigent access to health care in California's Orange County. Research strategies increased local awareness of barriers to access to care. Political strategies attempted to improve the county government's administrative procedures and financial support of services for the poor, to modify the practices of local health care institutions, and to influence state and national policies with implications for local indigent care. Legal strategies secured legal representation for persons unable to receive care, and persuaded the county to accept responsibility to provide nonemergency care to certain classes of indigents. Mayster, et al. discuss the strengths and weaknesses of these strategies, assess their impact, and offer encouragement to local advocacy efforts.
P73 The Rate Of Incidental Synchronous Pathology On Pet-ct Scans Performed For Thoracic Malignancy And Subsequent Impact On Lung Cancer Pathways
Authors: T. Jones, H. Curtis
Journal: Thorax (2014)

<h3>Introduction</h3> NICE (CG121) recommends that all patients potentially suitable for curative intent treatments are offered PET-CT, and that they are treated within 62 days of their urgent referral and within 31 days of the decision to treat. There are case reports and three large studies regarding incidental findings on PET-CT performed for thoracic malignancy. These studies were based in Sheffield, Australia and Switzerland, with a rate of significant incidental findings of 21%, 12% and 9% respectively. There are no studies regarding the impact on referral pathways. We aimed to identify the rate of incidental synchronous pathology on PET-CT for thoracic malignancy in our local population of 190,000 and the impact of these on referral pathways. We serve a local authority district ranked 43/326 in the English Index Multiple Deprivation in 2010 (rank of 1 being most deprived). <h3>Methods</h3> Identifying patients from our thoracic MDT database, we retrospectively analysed electronic patient records for those with synchronous pathology on PET-CT between November 2012 and October 2013. Data collected included primary diagnosis, synchronous pathology, referral timelines and reasons for delays. <h3>Results</h3> 108 patients had a PET-CT for investigation of thoracic malignancy. 29 incidental findings were found in 28 patients (28/108;26%); see chart-1. 20 patients (20/108;19%) required further investigation/referral for their synchronous pathology. 22 of these 28 patients were ultimately diagnosed and treated for thoracic malignancy. Referral to treatment was delayed in 8 patients (8/108;7%), but only in 1 (1/108;1%) as a direct result of management for their synchronous pathology. <h3>Conclusions</h3> A high number of patients undergoing PET-CT have synchronous pathology. Compared with previous UK data we found a higher rate of synchronous pathology. This may reflect a higher burden of disease in the North East of England. Synchronous findings have a limited impact on referral to treatment pathways. However they can result in more investigations and trips to hospital, which may have a psychological impact on patients already going through a stressful life event. Perhaps this should be highlighted at time of decision to perform PET-CT.
The clear vision of outsiders
Authors: Jane Smith
Journal: BMJ (2006)

It takes outsiders to see things with the most clarity. Thus, in our Health Policy debate this week—on whether the NHS should be more independent of government and politicians—it is two Americans, Don Berwick and Sheila Leatherman, who articulate most clearly what the NHS should be about and how it seems to have lost its way (p 254). “The NHS is not just a national treasure; it is a global treasure.” It needs “the time, space, and constancy of purpose to realise its enormous promise.”

Berwick and Leatherman, together with Stephen Thornton, Gwyn Bevan, and …
FUNDAMENTALS OF RURAL HEALTH WORK
Authors: W. F. DRAPER
Journal: JAMA (1923)

In the presence of a medical audience it is unnecessary to emphasize the need for public health work in the rural sections of our country. It is now a well known fact that the natural advantages which the rural districts possess in favor of a healthful existence are more than offset by the better health protection afforded the city dweller. Malaria and hookworm diseases are almost entirely of rural origin, and there is much more typhoid fever and dysentery in the country than in cities. Tuberculosis also is surprisingly prevalent in rural districts. Rural health work is bound to experience a tremendous development during the next ten years, and as the work grows it is important that certain fundamentals be borne in mind. These I shall deal with briefly. The first and greatest need is for the coordination of the health activities which are being introduced into rural communities. Under
PSYCHOMETRIC PERFORMANCE OF CHILDREN RECEIVING AMPHETAMINE (BENZEDRINE) SULFATE
Authors: CHARLES BRADLEY, EMILY GREEN
Journal: American Journal of Psychiatry (1940)

The effect of amphetamine sulfate upon the intelligence scores of 21 children was noted. Following therapeutic oral doses of 10 mg. and 20 mg. of the drug, performances on the revised Stanford- Binet scale and on a battery of psychomotor tests were not significantly affected. It is suggested that amphetamine sulfate may result in an apparent intellectual improvement in certain situations by its effect on the emotional attitude of the individual toward his task.
Altered expression and action of the low-affinity IgE receptor FcϵRII (CD23) in asthmatic airway smooth muscle
Authors: Hakon Hakonarson, Carrie Carter, Cecilia Kim, Michael M. Grunstein
Journal: Journal of Allergy and Clinical Immunology (1999)

Background: Changes in cell surface expression of certain immunoglobulin Fc receptors have been demonstrated in leukocytes isolated from the lungs of atopic asthmatic individuals. This, together with emerging evidence that Fc receptors can also be expressed and activated in non–bone marrow–derived cell types, including airway smooth muscle (ASM), raises the hypothesis that the atopic asthmatic ASM phenotype is associated with an altered endogenous expression and action of specific Fc receptors present in the ASM itself. Objective: The current study addressed the above hypothesis by examining (1) whether the expression of certain key Fc receptor subtypes for IgE and IgG is altered in ASM tissue isolated from human atopic asthmatic individuals and (2) whether this altered Fc receptor expression is comparably induced in naive human ASM tissue and cultured cells after their passive sensitization with human atopic asthmatic serum or IgE immune complexes. Methods: Messenger RNA and cell surface protein expression of the individual IgG receptor subtypes FcγRI, FcγRII, and FcγRIII, as well as the IgE receptor subtypes FcϵRI and FcϵRII, were examined in human ASM tissue isolated from atopic asthmatic and control (nonatopic/nonasthmatic) individuals. In addition, we examined the effects of passive sensitization of ASM tissue and cultured ASM cells with control serum, atopic asthmatic serum, or exogenously administered IgE immune complexes on Fc receptor expression and action (ie, induction of proinflammatory cytokine release). Results: The observations demonstrate that (1) human ASM tissue expresses messenger RNA and surface protein for FcϵRII, as well as for all the Fcγ receptor subtypes, (2) in contrast to unaltered Fcγ subtype expression, however, relative to control human ASM, FcϵRII is significantly up-regulated in inherently asthmatic ASM tissue, (3) up-regulated expression of FcϵRII represents, at least in part, an inducible phenomenon that is largely attributed to IgE immune complex–coupled activation of the receptor, and (4) the latter action is associated with FcϵRII-induced autologous elaboration of the proinflammatory cytokine, IL-1β, by the atopic sensitized ASM. Conclusion: These observations provide new evidence that human ASM tissue expresses FcϵRII in addition to all 3 subtypes of Fcγ receptors and that the expression of FcϵRII is selectively increased in atopic asthmatic ASM, a phenomenon associated with IgE immune complex/FcϵRII–mediated elaboration of IL-1β by the ASM itself. (J Allergy Clin Immunol 1999;104:575-84.)
Epigenetic Modification at Notch Responsive Promoters Blunts Efficacy of Inducing Notch Pathway Reactivation After Myocardial Infarction
Authors: Giulia Felician, Chiara Collesi, Marina Lusic, Valentina Martinelli, Matteo Dal Ferro, Lorena Zentilin, Serena Zacchigna, Mauro Giacca
Journal: Circulation Research (2014)

Rationale: The Notch pathway plays a key role in stimulating mammalian cardiomyocyte proliferation during development and in the early postnatal life; in adult zebrafish, reactivation of this pathway is also essential to drive cardiac regeneration after injury. Objective: We wanted to assess efficacy of Notch pathway stimulation in neonatal and adult hearts as a means to induce cardiac regeneration after myocardial infarction in mice. Methods and Results: In early postnatal life, cardiomyocyte exit from the cell cycle was paralleled by decreased Notch signaling and the establishment of a repressive chromatin environment at Notch-responsive genes, characterized by recruitment of the polycomb group enhancer of zeste homolog 2 methyltransferase and the acquisition of the histone 3 Lysine 27 trimethylation histone mark, as detected by chromatin immunoprecipitation. Forced Notch pathway activation by adenoassociated virus gene transfer of activated Notch1 or its ligand Jagged1 expanded the proliferative capacity of neonatal cardiomyocytes; this correlated with increased transcription of Notch target genes and maintenance of an open chromatin conformation at their promoters. The same adenoassociated virus vectors, however, were largely ineffective in stimulating cardiac repair after myocardial infarction in adult mice, despite optimal and long-lasting transgene expression. Analysis of Notch-responsive promoters in adult cardiomyocytes showed marks of repressed chromatin and irreversible CpG DNA methylation. Induction of adult cardiomyocyte re-entry into the cell cycle with microRNAs was independent from Notch pathway reactivation. Conclusions: Notch pathway activation is crucial in regulating cardiomyocyte proliferation during the early postnatal life, but it is largely ineffective in driving cardiac regeneration in adults, because of permanent epigenetic modification at Notch-responsive promoters.
A New Pharmacologic Action of CCI-779 Involves FKBP12-Independent Inhibition of mTOR Kinase Activity and Profound Repression of Global Protein Synthesis
Authors: Boris Shor, Wei-Guo Zhang, Lourdes Toral-Barza, Jessica Lucas, Robert T. Abraham, James J. Gibbons, Ker Yu
Journal: Cancer Research (2008)

The mammalian target of rapamycin (mTOR) inhibitor CCI-779 (temsirolimus) is a recently Food and Drug Administration-approved anticancer drug with efficacy in certain solid tumors and hematologic malignancies. In cell culture studies, CCI-779 at the commonly used nanomolar concentrations generally confers a modest and selective antiproliferative activity. Here, we report that, at clinically relevant low micromolar concentrations, CCI-779 completely suppressed proliferation of a broad panel of tumor cells. This "high-dose" drug effect did not require FKBP12 and correlated with an FKBP12-independent suppression of mTOR signaling. An FKBP12-rapamycin binding domain (FRB) binding-deficient rapamycin analogue failed to elicit both the nanomolar and micromolar inhibitions of growth and mTOR signaling, implicating FRB binding in both actions. Biochemical assays indicated that CCI-779 and rapamycin directly inhibited mTOR kinase activity with IC(50) values of 1.76 +/- 0.15 and 1.74 +/- 0.34 micromol/L, respectively. Interestingly, a CCI-779-resistant mTOR mutant (mTOR-SI) displayed an 11-fold resistance to the micromolar CCI-779 in vitro (IC(50), 20 +/- 3.4 micromol/L) and conferred a partial protection in cells exposed to micromolar CCI-779. Treatment of cancer cells with micromolar but not nanomolar concentrations of CCI-779 caused a marked decline in global protein synthesis and disassembly of polyribosomes. The profound inhibition of protein synthesis was accompanied by rapid increase in the phosphorylation of translation elongation factor eEF2 and the translation initiation factor eIF2 alpha. These findings suggest that high-dose CCI-779 inhibits mTOR signaling through an FKBP12-independent mechanism that leads to profound translational repression. This distinctive high-dose drug effect could be directly related to the antitumor activities of CCI-779 and other rapalogues in human cancer patients.
CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney
Authors: M. Lu
Journal: Journal of Clinical Investigation (2006)

The cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel plays vital roles in fluid transport in many epithelia. While CFTR is expressed along the entire nephron, its function in renal tubule epithelial cells remains unclear, as no specific renal phenotype has been identified in cystic fibrosis. CFTR has been proposed as a regulator of the 30 pS, ATP-sensitive renal K channel (Kir1.1, also known as renal outer medullar K [ROMK]) that is critical for K secretion by cells of the thick ascending limb (TAL) and distal nephron segments responsive to aldosterone. We report here that both ATP and glibenclamide sensitivities of the 30 pS K channel in TAL cells were absent in mice lacking CFTR and in mice homozygous for the deltaF508 mutation. Curcumin treatment in deltaF508-CFTR mice partially reversed the defect in ATP sensitivity. We demonstrate that the effect of CFTR on ATP sensitivity was abrogated by increasing PKA activity. We propose that CFTR regulates the renal K secretory channel by providing a PKA-regulated functional switch that determines the distribution of open and ATP-inhibited K channels in apical membranes. We discuss the potential physiological role of this functional switch in renal K handling during water diuresis and the relevance to renal K homeostasis in cystic fibrosis.
How district health authorities organise cervical screening.
Authors: A Elkind, A Eardley, R Thompson, A Smith
Journal: BMJ (1990)

OBJECTIVES--To examine how district health authorities organised cervical screening with respect to Department of Health guidelines and to determine their assessment of the problems encountered. DESIGN--Postal questionnaire sent to all 190 district health authorities in England in 1989. PARTICIPANTS--190 District health authorities in England. MAIN OUTCOME MEASURES--Population coverage of screening, quality of smear testing, and follow up of abdominal test results in comparison with national guidelines for district cervical screening services, and problems encountered by districts. RESULTS--Replies were received from 178 (94%) of districts, in 143 of which the person named as responsible for cervical screening contributed. All districts implemented a computer managed scheme, 150 by the target date of 31 March 1988, but not all of these conformed with the guidelines. At the time of the survey only just over half called women in the target age group of 20-64 and only 70% expected to meet the target date of 13 March 1993 for completing the call. Considerable variation was evident among the schemes with regard to how they dealt with issues related to population coverage, quality of testing, and follow up of abnormal results. The problems most commonly identified by the districts (n = 174) were laboratory workload (107, 61%), computer software (104, 60%), availability of resources (78, 45%), non-attendance (77, 44%), rate of opportunistic screening (62, 36%), and investigation and treatment (60, 34%). CONCLUSIONS--Current practice in running cervical screening schemes needs to be examined to determine the extent to which it contributes to the goal of reducing mortality from cervical cancer.
Excess mortality among psychiatric patients
Authors: E. Masterson
Journal: JAMA (1985)

To the Editor.—  We would like to discuss some points raised by Black et al. 1 The phenomenally high incidence of deaths from suicides and accidents—32% of all deaths and 67% of excess deaths—remains difficult to comprehend despite an awareness of the increased mortality from suicide in psychiatric populations and the strong association between physical and psychiatric disorder. 2 In our own study, 3 schizophrenics died at a younger age than members of the general population as a result of an excess of cases of pneumonia as well as an increased incidence of suicide (18.9% died of pneumonia; 6.6% committed suicide—9.7% of males and 3.3% of females). One wonders about the difference between American and Irish smoking patterns and the distribution of unnatural deaths among the different subclasses of psychiatric disorder in the study by Black et al.  The authors attempt to discover common themes in mortality patterns. It seems
Abstract 1455: <i>In vivo</i> circulating tumor cells in blood, lymph and cerebrospinal fluid: dynamic cross-correlations and amplification for cancer diagnosis.
Authors: Ekaterina I. Galanzha
Journal: Cancer Research (2013)

Abstract We introduced a new platform of multicolor multi-fluid in vivo flow cytometry for real-time ultrasensitive molecular detection and counting of circulating tumor cells (CTCs) and their subpopulations the blood, lymph and cerebrospinal fluid's (CSF) flows. To achieve these goals we integrated multicolor photoacoustic (PA), photothermal (PT) and fluorescent flow cytometry, and combined this technical platform with multiplex molecular targeting strategy using low-toxicity, gold-based functionalized nanoparticles as PA/PT high-contrast agents or genetically encoded proteins (e.g., green fluorescent protein [GFP]) as fluorescent labels. This platform can provide also label-free detection mode using intrinsic (e.g., melanin) molecular labels. The advantages of this new generation of flow cytometries are (1) improving sensitivity by at least a two-order of magnitude compared to available CTC-assays, and (2) significantly extending biomedical applications compared to existing in vivo flow cytometries. Using preclinical tumor-bearing mouse models of metastatic melanoma and breast cancer, and spiked human blood samples, we demonstrated that our technology can overcome great challenge in cancer research related to monitoring lymph, CSF and blood CTCs at single-cell levels in the natural environment in vivo over the long-term period of metastatic disease development from an early micrometastatic stage to deadly multiple macro-metastases. The obtained results allowed us to estimate in vivo cross-correlations between lymph, CSF and blood CTC counts, size of primary tumor and metastasis (micrometastasis) progression. We also showed that the presented approach can break some important diagnostic limitations of existing methods (e.g., low sensitivity) and potentially permits prevention, or at least inhibition, of metastatic progression. Taking into account the safe nature of the PA technology, we anticipate its quick translation for use in humans. Citation Format: Ekaterina I. Galanzha. In vivo circulating tumor cells in blood, lymph and cerebrospinal fluid: dynamic cross-correlations and amplification for cancer diagnosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1455. doi:10.1158/1538-7445.AM2013-1455 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Orthopaedic Sports Medicine: Principles and Practice
Authors: Angela D. Smith
Journal: JAMA (1994)

<b>Pediatric and Adolescent Sports Medicine</b>, edited by Carl L. Stanitski, Jesse C. DeLee, and David Drez, Jr, 410 pp, with illus, $125, ISBN 07-216-32615, Philadelphia, Pa, WB Saunders Co, 1994. The two-volume set edited by DeLee and Drez and the companion volume on pediatric sports medicine, primarily edited by Stanitski, are targeted at orthopedic surgeons, who will appreciate the specific details regarding surgical indications and techniques, but they are likely to be consulted often by all physicians who provide musculoskeletal care for athletes—for both excellent practical clinical tips and heavily referenced discussions of basic science topics. The richly detailed chapters on musculoskeletal injuries include discussions of injury prevention, rehabilitation, and criteria for return to play. The sections on medical problems of athletes also recommend specific criteria for sports participation. Roughly a quarter of the adult sports medicine text covers basic science and medical topics. The basic science authors are well