tbuckley/cabot-search huggingface dataset:
Promise and Perils for Patients and Physicians
Authors: Richard L Kravitz, Sophia Chang
Journal: New England Journal of Medicine (2005)

On January 1, 2006, the Medicare Prescription Drug Improvement and Modernization Act (MMA) will become a fact of life for 42 million Medicare beneficiaries and their physicians. For the past three months, America's older citizens have been barraged with educational and marketing initiatives for various drug plans, though it has been an uphill battle: an October poll indicated that 61 percent did not understand the program “somewhat well” and 54 percent did not intend to sign up for coverage.1 The task of sorting through the myriad alternatives will fall squarely on patients and their physicians. The federal government has posted . . .
Abstract 1224: Intratumoral chitosan/IL-12 neoadjuvant to tumor resection is safe and generates tumor specific immunity.
Authors: Jimmy Loc Nhu Vo, Lirong Yang, David Zaharoff
Journal: Cancer Research (2013)

Abstract Interleukin-12 (IL-12) is a potent antitumor cytokine that exhibits significant clinical toxicities after systemic administration. Local delivery strategies capable of maintaining high concentrations of IL-12 in the tumor microenvironment while minimizing systemic exposure are under investigation. We have previously shown that intratumoral injections of IL-12 co-formulated with a solution of chitosan (chitosan/IL-12) can eliminate established primary tumors. Chitosan is an abundant, natural polysaccharide derived primarily from the exoskeletons of crustaceans. Chitosan has been shown to maintain high local concentrations of protein antigens and cytokines through viscous, electrostatic and bioadhesive interactions. Because of IL-12’s well documented ability to generate tumor-specific cell-mediated immunity, we are exploring the anti-metastatic potential of intratumoral chitosan/IL-12 immunotherapy in a highly metastatic model of breast cancer (4T1). Previously, we have shown that intratumoral chitosan/IL-12 neoadjuvant prior to tumor resection confers long-term survival benefits and reduces metastasis. Recent studies reveal that chitosan/IL-12 is safe and generates tumor-specific systemic immunity to confer long-term survival benefits. Specifically, splenocytes from long term survivors demonstrated anti-tumor immunity in a cytotoxic T-lymphocyte (CTL) killing assay. After 1 week of in vitro stimulation, splenocytes were found to lyse approximately 40% of target tumor cells at an effector: target ratio of 50:1. In addition, toxicological studies reveal that chitosan/IL-12 does not adversely affect leukocyte levels or hematocrit. Based on data obtained thus far, intratumoral chitosan/IL-12 shows promising potential as a neoadjuvant immunotherapy to reduce metastatic disease while minimizing the toxicities that hindered the progress of IL-12 based cancer immunotherapy. Citation Format: Jimmy Loc Nhu Vo, Lirong Yang, David Zaharoff. Intratumoral chitosan/IL-12 neoadjuvant to tumor resection is safe and generates tumor specific immunity. [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 1224. doi:10.1158/1538-7445.AM2013-1224
CD66+ Cells in Cervical Precancers Are Partially Differentiated Progenitors with Neoplastic Traits
Authors: Chitra Pattabiraman, Shiyuan Hong, Vignesh K. Gunasekharan, Annapurna Pranatharthi, Jeevisha Bajaj, Sweta Srivastava, H. Krishnamurthy, Aswathy Ammothumkandy, Venkat G. Giri, Laimonis A. Laimins, Sudhir Krishna
Journal: Cancer Research (2014)

Cervical cancers, a malignancy associated with oncogenic papilloma viruses, remain a major disease burden in the absence of effective implementation of preventive strategies. CD66(+) cells have previously been identified as a tumor-propagating subset in cervical cancers. We investigated the existence, differentiation state, and neoplastic potential of CD66(+) cells in a precancer cell line harboring HPV31b episomes. The gene expression profile of CD66(high) cells overlaps with differentiated keratinocytes, neoplastic mesenchymal transition, cells of the squamocolumnar junction, and cervical cancer cell line-derived spheroids. There is elevated expression of DNMT1, Notch1, and the viral gene product E1⁁E4 in CD66(high) cells. Thus, CD66(high) cells, in the absence of differentiating signals, express higher levels of key regulators of keratinocytes stemness, differentiation, and the viral life cycle, respectively. We also find a striking association of neoplastic traits, including migration, invasion, and colony formation, in soft agar with CD66(high) cells. These properties and a distinct G2-M-enriched cell-cycle profile are conserved in cells from cervical cancers. Principally, using a precancerous cell line, we propose that CD66(high) cells have an intermediate differentiation state, with a cellular milieu connected with both viral replication and neoplastic potential, and validate some key features in precancer lesions. Such pathophysiologically relevant systems for defining cellular changes in the early phases of the disease process provide both mechanistic insight and potential therapeutic strategies. Collectively, our data provide a rationale for exploring novel therapeutic targets in CD66(+) subsets during cancer progression.
Exhaled Nitric Oxide and Bronchoalveolar Lavage Nitrite/Nitrate in Active Pulmonary Sarcoidosis
Authors: DEARBHAILE M. O'DONNELL, JOHN MOYNIHAN, GERALDINE A. FINLAY, VERA M. KEATINGS, CLARE M. O'CONNOR, PAUL McLOUGHLIN, MUIRIS X. FITZGERALD
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Increased exhaled nitric oxide (NO) may reflect respiratory tract inflammation in untreated asthmatics. We compared exhaled NO and bronchoalveolar lavage (BAL) nitrate/nitrite (NO3 −/NO2 −) in 10 patients who had untreated, active pulmonary sarcoidosis with those of normal control subjects. Exhaled NO concentrations, determined by chemiluminescence, were similar in patients and control subjects (peak NO concentration of patients [mean ± SD]: 13.6 ± 5.9 parts per billion [ppb], peak NO concentration of control subjects: 11.2 ± 5.7 ppb, p = 0.32; mean alveolar NO concentration of patients: 7.8 ± 4.4 ppb, mean alveolar NO concentration of control subjects: 7.1 ± 4.2 ppb, p = 0.70; end-tidal NO concentration of patients: 6.9 ± 4.5 ppb, end-tidal NO concentration of control subjects: 6.6 ± 4.0 ppb, p = 0.60). BAL NO2 − was assayed using a modified Griess reaction after reduction of NO3 − to NO2 −. There was no significant difference in mean BAL NO2 − concentrations, expressed as nanomoles per milliliter of epithelial lining fluid (patients: 544 nmol/ml, control subjects: 579 nmol/ ml, p = 0.81) or as nanomoles per milliliter of BAL fluid (patients: 6.7 nmol/ml, control subjects: 5.7 nmol/ml, p = 0.41). These data suggest that excess NO generation does not accompany the respiratory tract inflammation of pulmonary sarcoidosis. O'Donnell DM, Moynihan J, Finlay GA, Keatings VM, O'Connor CM, McLoughlin P, Fitzgerald MX. Exhaled nitric oxide and bronchoalveolar lavage nitrite/nitrate in active pulmonary sarcoidosis.
Detection of Bacteremia in Adults: Consequences of Culturing an Inadequate Volume of Blood
Authors: Leonard A. Mermel
Journal: Annals of Internal Medicine (1993)

The yield of blood cultures depends on the volume of blood cultured. We recently discovered that 15% of blood-culture specimens from adults in our hospital were being collected in 3.5-mL pediatric tubes and that another 5%, drawn in 10-mL adult tubes, contained less than 5 mL of blood. A comparison of 829 matched pairs of standard-volume (mean, 8.7 mL) and low-volume (mean, 2.7 mL) blood cultures showed that standard-volume cultures had a substantially higher detection rate for bloodstream infection than did low-volume cultures (92% compared with 69%; difference, 23% [95% CI, 9% to 37%]; P < 0.001). Our data, together with an analysis of previous studies, show that the yield of blood cultures in adults increases approximately 3% per millilitre of blood cultured. A survey of 158 U.S. clinical microbiology laboratory directors in the American Society of Clinical Pathologists showed that only 20% of 71 responding laboratories record the volume of blood submitted for culture and that the practice of culturing suboptimal volumes of blood from adults is widespread. Clinical laboratories should routinely monitor the volume of blood cultured as a quality-assurance measure. Blood-culture specimens from adults should not be drawn using small pediatric tubes.
Rubella virus and rheumatoid arthritis.
Authors: H Hart, B P Marmion
Journal: Annals of the Rheumatic Diseases (1977)

A collection of synovial fibroblasts from 19 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthrosis or other non-RA disease has been examined for rubella virus antigens by immunofluorescence and radioimmunoassay with negative results. Eluates of synovial membrane prepared under conditions likely to dissociate antigen-antibody complexes have shown no rubella antibody. A serological survey of RA patients and those with other forms of arthritis has shown no differences in the frequency or levels of rubella haemagglutination-inhibiting antibody. These results provide little support for various hypotheses that a persistent infection with rubella virus underlies or initiates the rheumatoid process.
Disparate mechanisms of antifolate resistance provoked by methotrexate and its metabolite 7-hydroxymethotrexate in leukemia cells: implications for efficacy of methotrexate therapy
Authors: Kambiz Fotoohi, Gerrit Jansen, Yehuda G Assaraf, Lilah Rothem, Michal Stark, Ietje Kathmann, Jacek Gregorczyk, Godefridus J Peters, Freidoun Albertioni
Journal: Blood (2004)
NHS managers are more worried about financial squeeze than reform, survey finds
Authors: A. Gulland
Journal: BMJ (2011)

A survey of NHS managers has found that their biggest worry about the next 12 months is the financial pressure facing the health service, not the government’s reforms of the NHS.

The NHS Confederation, which represents health service managers, surveyed its members in January, asking them to list in order the three issues of greatest concern over the coming year.

The survey of 279 senior managers showed that, despite the headlines about the changes to the health service, financial instability is the main worry. 

Of the 252 managers who responded to the question about their concerns, two thirds said that balancing finances and making cost savings would be one of their top three concerns, with 31% saying this would be the most important. …
Role of Delayed Tc-99m HMPAO Labeled Leukocyte Scintigraphy In the Diagnosis of Coronary Mycotic Aneurysm
Authors: Vani Vijayakumar, Rajeev K. Shah
Journal: Clinical Nuclear Medicine (2005)

Coronary mycotic aneurysms are rare with a poor prognosis. Atherosclerosis often predisposes to aneurysmal dilatation. In children, Kawasaki disease and in adults trauma, vasculitis, syphilis, dissection, and postcoronary angioplasty contribute to coronary mycotic aneurysms. Radiolabeled leukocytes have been used in the diagnosis of prosthetic valve endocarditis and vascular graft infections. Abnormal accumulation of radiolabeled leukocytes have also been reported in infra renal aortic aneurysms. We present a case of a coronary mycotic aneurysm where delayed Tc-99m HMPAO labeled leukocyte imaging played an important role leading to the diagnosis.
PRISM: Enmeshment of Illness and Self-Schema
Authors: Fiona Denton, Louise Sharpe, Leslie Schrieber
Journal: Psychotherapy and Psychosomatics (2003)

&lt;i&gt;Background:&lt;/i&gt; The Pictorial Representation of Illness and Self Measure (PRISM) is a recently developed tool purported to assess burden of suffering due to illness. The nature of the PRISM task suggests a conceptual link to the illness self-schema construct hypothesised to be present in some individuals with chronic illness. This study investigates the relationship between PRISM and schema as measured by cognitive bias. &lt;i&gt;Methods:&lt;/i&gt; 43 patients with systemic lupus erythematosus (SLE) completed an information-processing task involving endorsement of positive and negative illness words as descriptors of themselves, followed by free recall of the words. The outcome measures were endorsement and recall bias for negative illness words. Patients also completed the PRISM task and were assessed on other physical and psychological variables. &lt;i&gt;Results:&lt;/i&gt; PRISM did not correlate significantly with age, depression, functional impairment or disease activity. In a multiple regression analysis, only recall bias made an independent contribution to PRISM. &lt;i&gt;Conclusions:&lt;/i&gt; Illness self-schema appears to play a significant role in determining the way in which SLE patients complete the PRISM task. This is discussed in light of a schema enmeshment model recently proposed in the cognitive bias literature.
Increased Exchange Current but Normal Ca <sup>2+</sup> Transport via Na <sup>+</sup> -Ca <sup>2+</sup> Exchange During Cardiac Hypertrophy After Myocardial Infarction
Authors: Ana Maria Gómez, Beat Schwaller, Hartmut Porzig, Guy Vassort, Ernst Niggli, Marcel Egger
Journal: Circulation Research (2002)

Hypertrophied and failing cardiac myocytes generally show alterations in intracellular Ca 2+ handling associated with changes in the contractile function and arrhythmogenicity. The cardiac Na + -Ca 2+ exchange (NCX) is an important mechanism for Ca 2+ extrusion and cell relaxation. Its possible involvement in changes of excitation-contraction coupling (EC-coupling) with disease remains uncertain. We analyzed the NCX function in rat ventricular myocytes 5 to 6 months after experimental myocardial infarction (PMI) produced by left coronary artery ligation and from sham-operated (SO) hearts. Caged Ca 2+ was dialyzed into the cytoplasm via a patch-clamp pipette and Ca 2+ was released by flash photolysis to activate NCX and measure the associated currents ( I NaCa ), whereas [Ca 2+ ] i changes were simultaneously recorded with a confocal microscope. I NaCa density normalized to the [Ca 2+ ] i jumps was 2.6-fold higher in myocytes from PMI rats. The level of total NCX protein expression in PMI myocytes was also increased. Interestingly, although the I NaCa density in PMI cells was larger, PMI and SO myocytes presented virtually identical Ca 2+ transport via the NCX. This discrepancy was explained by a reduced surface/volume ratio (34.8%) observed in PMI cells. We conclude that the increase in NCX density may be a mechanism to maintain the required Ca 2+ extrusion from a larger cell to allow adequate relaxation.
Protein tyrosine kinase syk is associated with and activated by the il-2 receptor: Possible link with the c-myc induction pathway
Authors: Yasuhiro Minami, Yoko Nakagawa, Atsuo Kawahara, Tadaski Miyazaki, Kiyonao Sada, Hirohei Yamamura, Tadatsugu Taniguchi
Journal: Immunity (1995)
Second messengers, ion channels and pharmacology of airway smooth muscle
Authors: I.P. Hall
Journal: European Respiratory Journal (2000)

The airway smooth muscle cell is the chief effector cell governing the control of airway calibre in the human lung. The contractile state of the airway smooth muscle cell is predominantly influenced by the balance of constrictor and relaxant stimuli. Agents such as histamine and acetylcholine cause airway smooth muscle cells to contract through activation of specific cell surface receptors and engagement of signal transduction pathways and/or ion channels. The predominant pathway mediating constriction is activation of phospholipase C, with release of inositol 1,4,5-triphosphate and elevation of intracellular calcium levels. Relaxation is brought about predominantly by stimulation of adenylyl cyclase-coupled receptors (e.g. the beta2-adrenoceptor) resulting in elevation of cell cyclic adenosine monophosphate content. Complex crosstalk occurs between both of these pathways and also ion channels expressed on the airway smooth muscle cell membrane, leading to careful regulation of airway smooth muscle tone. A greater understanding of the mechanisms governing control of these pathways will lead to the identification of novel therapeutic targets which will in turn lead to new agents for the treatment of asthma.
Early Results of a Simplified Method of Mitral Valve Annuloplasty
Authors: John A. Odell, Hartzell V. Schaff, Thomas A. Orszulak
Journal: Circulation (1995)

Background We hypothesized that a simple, unmeasured posterior annuloplasty technique (two thirds of a 27-mm Duran ring) offered advantages of standardization and ease of insertion. Methods and Results A consecutive series of all patients (n=418; median age, 67 years) having mitral valve repair performed by two surgeons was analyzed to determine the outcome of three different annuloplasty techniques: commissural annuloplasty (n=124), complete ring annuloplasty (n=113), and an unmeasured, posterior, partial ring annuloplasty (n=181). Intraoperatively, before repair, severity of mitral regurgitation as measured by double sampling dye curves and transesophageal echocardiography was similar in all three groups; after mitral valve repair, intraoperative assessment showed a similar degree of reduction in regurgitation in the three annuloplasty groups. Before hospital dismissal, transthoracic echocardiography demonstrated that the mean mitral valve areas and gradients were similar in the three groups; more patients having commissural annuloplasty were classified as having grade II or greater regurgitation. Mortality (n=7, 1.7%) and need for reoperation (n=8, 1.9%) was low in all groups despite the fact that additional procedures were performed in 48.8% of patients. Durations of cardiopulmonary bypass and aortic cross-clamping were significantly less in patients having commissural or posterior annuloplasties compared with those receiving a complete ring annuloplasty. Conclusions These early results indicate that the posterior annuloplasty method is reproducible and expeditious. Postoperative valve function as assessed by degree of regurgitation, transvalvular gradient, and valve area was similar to that obtained by measured, complete ring annuloplasty and superior to that found in patients having commissural annuloplasty.
Clinical Lecture on a Case of Chyluria
Authors: B. Bramwell
Journal: BMJ (1897)

THIS, gentlemen, is a remarkable specimen of urine.It looks exactly like milk.The condition-chyluria-is rare in this country.I myself have only seen one other instance in which the milky appearance was so marked, though I have met with one or two other slight cases.I therefore take the opportunity of showing you the urine.I have two specimens of the urine.Let us examine their characters more carefully.TThe first specimen?which was passed before breakfast is you will see, only slightly milky; it has a reddish tint.Phe second specimen, which was passed after breakfast, is perfectly white; it looks like pure milk.After standing a thick, oream-like layer collects on the top of the urine.Ihe reac- tion of the urine is strongly acid; the specific gravity 1024; the
Malignant hypertension due to musculo-mucoid intimal hyperplasia of intrarenal arteries. Absence of renal fibrinoid necrosis.
Authors: J A Pitcock, J G Johnson, L Share, F E Hatch, S R Acchiardo, W D Black, E E Muirhead
Journal: Circulation Research (1975)

Severe essential hypertension in a subset of American black subjects is associated with marked stenosis of interlobular arteries and arterioles of the kidneys, observed by renal biopsy and binephrectomy specimens. The interlobular arterial stenosis is caused by marked thickening of the intima due mainly to the presence of smooth muscle cells, basement membrane material, and acid mucopolysaccharide. Because of this makeup, we propose the term "musculo-mucoid intimal hyperplasia" for this lesion. The media of these arteries appears maximally dilated, and by electron microscope displays degenerative changes of the smooth muscle cells. The arterioles are thickened, due mainly to hyalinization, but also due to the musculo-mucoid change (onionskin effect). The smooth muscle cells are degenerated and atrophic. These patients do not exhibit fibrinoid necrosis of the arteries, arterioles, and glomeruli, presumably because of the rapidity of the development of the arterial stenotic lesion. Accordingly, the glomeruli are destroyed by ischemia, and there is no evidence of glomerulitis (no "Kombinations" form of Fahr). A unifying hypothesis concerning renal hypertensive arterial disease is suggested by these studies. This hypothesis places the main emphasis for all the morphological expressions of the intrinsic visceral vasculature on changes involving the main functional unit of the vessel wall, the medical smooth muscle.
New patients' forums are no substitute for community health councils, MPs say
Authors: A. Gulland
Journal: BMJ (2003)

A committee of MPs has called for community health councils to be given a seven month reprieve because of the confusion surrounding the new system of involving patients in the NHS.

A report by the Commons health select committee called for the community health councils' period of operation to be extended from December 2003 until July 2004 after it cast doubt on how many of the new patient involvement bodies were in place.

MPs said that none of the new bodies had the “overview, independence or direct means for patients to input into local …
Research paper does not show causal link between benzodiazepine use and diagnosis of dementia
Authors: I. T. S. Coyle-Gilchrist, L. F. Peck, J. B. Rowe
Journal: BMJ (2012)

The prospective population based study by Billioti de Gage and colleagues shows an association between benzodiazepine use and the subsequent diagnosis of dementia but it does not show causality.1

Sleep disturbance is a common feature of many neurodegenerative diseases and may precede dementia by years.2 For example, the 10 year risk of a …
HIV Testing of Pregnant Women and Newborns-Reply
Authors: Ruth R. Faden
Journal: JAMA (1991)

<h3>In Reply. —</h3> Wachter et al take exception to our position on targeting, raising many of the same objections we discussed and refuted in our article. Interestingly, they do not engage any of our counterarguments, nor do they confront the central issue of whether it is in the interests of public health to restrict educational programs to only those women who are at highest risk. Also, it should be noted that our rejection of targeted policies for HIV education and testing of pregnant women, new mothers, and newborns is not categorical. We specifically endorse varying the intensity of the educational effort in accord with the significance of HIV infection and drug use in local communities. Dr Jensen objects to our position that testing should be voluntary. He believes that policies of mandatory screening and contact tracing can reduce HIV transmission rates. Insofar as this position is correct, it argues for