tbuckley/cabot-search huggingface dataset:
Relationship Between Age and Axillary Lymph Node Involvement in Women With Breast Cancer
Authors: Hans Wildiers, Ben Van Calster, Lonneke V. van de Poll-Franse, Wouter Hendrickx, Jo Røislien, Ann Smeets, Robert Paridaens, Karen Deraedt, Karin Leunen, Caroline Weltens, Sabine Van Huffel, Marie-Rose Christiaens, Patrick Neven
Journal: Journal of Clinical Oncology (2009)

Purpose To study the relation between the presence of axillary lymph node (LN) involvement and age in breast cancer. Patients and Methods The breast cancer database of the University Hospitals Leuven contains complete data on 2,227 patients with early breast cancer consecutively treated between 2000 and 2005. A multivariate piecewise logistic regression model was used to analyze LN involvement in relation to age at diagnosis. A similar analysis was then performed on a large, independent, population-based database from the Eindhoven Cancer Registry to investigate whether the effects of the Leuven model could be replicated. Results We observed a piecewise effect of age. That is, women up to 70 years of age were less likely to have positive LNs with increasing age (odds ratio per 10-year increase, 0.87). In contrast, older women were more likely to have positive LNs with increasing age. However, for older women, the effect of age interacted with tumor size (P = .0044), suggesting that increasing age is associated with increased risk of LN involvement, mainly in small tumors. These findings were replicated in the Eindhoven Cancer Registry database. Conclusion Axillary LN involvement varies with age at diagnosis; its probability decreases with increasing age up to the age of approximately 70 years, but increases again thereafter. However, this increase is mainly seen in smaller tumors and suggests a different behavior of small breast cancers in older adult patients. We hypothesize that decreased immune defense mechanisms, related with aging, may play a role in earlier invasion into LNs.
Fibrinogen and factor XIII A-subunit genotypes interactively influence C-reactive protein levels during inflammation
Authors: Berthold Hoppe, Thomas Häupl, Alla Skapenko, Sabine Ziemer, Rudolf Tauber, Abdulgabar Salama, Hendrik Schulze-Koops, Gerd-Rüdiger Burmester, Thomas Dörner
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Fibrinogen is a target of autoimmune reactions in rheumatoid arthritis (RA). Fibrin(ogen) derivatives are involved in inflammatory processes and the generation of a stable fibrin network is necessary for sufficient inflammation control. As the density and stability of fibrin networks depend on complex interactions between factor XIIIA (F13A) and fibrinogen genotypes, the authors studied whether these genotypes were related to C-reactive protein (CRP) levels during acute-phase reactions. <h3>Methods</h3> Association between α-fibrinogen (FGA), β-fibrinogen (FGB) and F13A genotypes with CRP levels was tested in two cohorts with longitudinal CRP measurements. Discovery and replication cohorts consisted of 288 RA (913 observations) and 636 non-RA patients (2541 observations), respectively. <h3>Results</h3> Genotype FGB −455G&gt;A (rs1800790) was associated with CRP elevations (≥10 mg/l) in both cohorts (RA, OR per allele 0.69, p=0.0007/P<sub>adj</sub>&lt;0.015; non-RA, OR 0.70, p=0.0004/p<sub>adj</sub>&lt;0.02; combined, OR 0.69, p&lt;10<sup>−5</sup>/p<sub>adj</sub>=0.001). Genotype F13A 34VV (rs5985) was conditional for the association of FGB −455G&gt;A with CRP as indicated by a clear restriction on F13A 34VV individuals and a highly significant heterogeneity between F13A 34VV and F13A 34L genotypes (p&lt;10<sup>−5</sup>, p<sub>adj</sub>=0.001). In both cohorts, mean CRP levels significantly declined with ascending numbers of FGB −455A alleles. Genotype FGA T312A (rs6050) exhibited opposite effects on CRP compared with FGB −455G&gt;A. Again, this relation was dependent on F13A V34L genotype. <h3>Conclusion</h3> Novel genetic determinants of CRP completely unrelated to previously known CRP regulators were identified. Presumably, these haemostatic gene variants modulate inflammation by influencing fibrin crosslinking. These findings could give new perspectives on the genetic background of inflammation control.
CD19-Targeted T Cells Rapidly Induce Molecular Remissions in Adults with Chemotherapy-Refractory Acute Lymphoblastic Leukemia
Authors: Renier J. Brentjens, Marco L. Davila, Isabelle Riviere, Jae Park, Xiuyan Wang, Lindsay G. Cowell, Shirley Bartido, Jolanta Stefanski, Clare Taylor, Malgorzata Olszewska, Oriana Borquez-Ojeda, Jinrong Qu, Teresa Wasielewska, Qing He, Yvette Bernal, Ivelise V. Rijo, Cyrus Hedvat, Rachel Kobos, Kevin Curran, Peter Steinherz, Joseph Jurcic, Todd Rosenblat, Peter Maslak, Mark Frattini, Michel Sadelain
Journal: Science Translational Medicine (2013)

Five adults with chemotherapy-refractory B-ALL were induced into molecular remissions after treatment with CD19 CAR-targeted T cells.
DIAGNOSIS AND TREATMENT OF THE SEXUAL OFFENDER: A NINE-YEAR STUDY
Authors: ASHER R. PACHT, SEYMOUR L. HALLECK, JOHN C. EHRMANN
Journal: American Journal of Psychiatry (1962)

After 9 years of experience with this law, we are convinced that a program which embodies the principles of indeterminate sentencing and psychiatric treatment is both workable and useful. We feel that it is the best approach currently available through which society can deal with the agonizing problem of the sex offender. We would be negligent, however, if we did not emphasize some of the problems and shortcomings of our own program. Obviously even an enlightened prison setting is not an ideal environment in which to conduct a flexible treatment program(8, 16). Until we can build our own"prison-hospital" for this group of offenders, we are forced to make many compromises which may not be therapeutic. Finding adequately trained therapists to work in a correctional environment remains a constant problem(19). We do not feel that we are anywhere close to giving optimum psychotherapy to each offender who can benefit thereby. A constantly haunting problem is our inability, because of the statutory requirements, to set up adequate control studies which would afford scientific validity to our work. Perhaps the most important issue raised by our experience involves the frightening responsibilities which the therapists must assume. A psychiatrist or psychologist in our sex deviate program often must step out of his traditional clinical role; he makes crucial decisions which effect the liberties of his fellowman. There is no room for an arrogant and dogmatic attitude. If we are to become involved in the problems of social justice, we must be prepared to assume the overwhelming responsibilities with sincere humility as well as scientific fervor.
Four emergency departments in London to be downgraded
Authors: A. O'Dowd
Journal: BMJ (2013)

Local NHS commissioners have taken the controversial decision to downgrade four emergency departments in London despite strong resistance from local doctors, the community, and a local authority.

Following public consultation, a business case was made for the Shaping a Healthier Future programme, which concerned the provision of healthcare in North West London.1 NHS North West London’s joint committee of primary care trusts (JCPCT) has agreed with all recommendations made in the business case report, confirming its decision on 19 February.

The decision means that emergency departments at Charing Cross, Central Middlesex, Hammersmith, and Ealing hospitals will be downgraded to urgent care centres, while an additional £190m (€220m; $290m) will be invested …
Involving users in the delivery and evaluation of mental health services: systematic review
Authors: Emma L Simpson, Allan O House
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To identify evidence from comparative studies on the effects of involving users in the delivery and evaluation of mental health services. <b>Data sources:</b> English language articles published between January 1966 and October 2001 found by searching electronic databases. <b>Study selection:</b> Systematic review of randomised controlled trials and other comparative studies of involving users in the delivery or evaluation of mental health services. <b>Data extraction:</b>Patterns of delivery of services by employees who use or who used to use the service and professional employees and the effects on trainees, research, or clients of mental health services. <b>Results:</b> Five randomised controlled trials and seven other comparative studies were identified. Half of the studies considered involving users in managing cases. Involving users as employees of mental health services led to clients having greater satisfaction with personal circumstances and less hospitalisation. Providers of services who had been trained by users had more positive attitudes toward users. Clients reported being less satisfied with services when interviewed by users. <b>Conclusions:</b> Users can be involved as employees, trainers, or researchers without detrimental effect. Involving users with severe mental disorders in the delivery and evaluation of services is feasible.
Sequencing and analysis of the genome of the Whipple's disease bacterium Tropheryma whipplei
Authors: Stephen D Bentley, Matthias Maiwald, Lee D Murphy, Mark J Pallen, Corin A Yeats, Lynn G Dover, Halina T Norbertczak, Gurdyal S Besra, Michael A Quail, David E Harris, Axel von Herbay, Arlette Goble, Simon Rutter, Robert Squares, Stephen Squares, Bart G Barrell, Julian Parkhill, David A Relman
Journal: The Lancet (2003)
P53 expression and human papillomavirus infection in transplant recipients and in patients with epidermodysplasia verruciformis
Authors: J.M. McGregor, P.H. McKee, M. Khorshid, C.M. Proby
Journal: British Journal of Dermatology (1996)

Journal Article P53 expression and human papillomavirus infection in transplant recipients and in patients with epidermodysplasia verruciformis Get access J.M. McGregor, J.M. McGregor Department of Photobiology, St John's Institute of Dermatology, St Thomas’Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.H. McKee, P.H. McKee Department of Histopathology, St Thomas’Hospital, Lambeth Palace Road, London SE1 7EH, U.K. Search for other works by this author on: Oxford Academic Google Scholar M. Khorshid, M. Khorshid Department of Dermatology, Royal London Hospital, Whitechapel Road, London E1 1BB, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.M. Proby C.M. Proby Department of Experimental Dermatology, Royal London Hospital Medical School, 56 Ashfield Street, London E1 2BL, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 134, Issue 2, 1 February 1996, Page 374, https://doi.org/10.1111/j.1365-2133.1996.tb07637.x Published: 01 February 1996
Diagnosis and Initial Management of Obstructive Sleep Apnea without Polysomnography
Authors: Alan T. Mulgrew, Nurit Fox, Najib T. Ayas, C. Frank Ryan
Journal: Annals of Internal Medicine (2007)

Background: Polysomnography (PSG), despite limited availability and high cost, is currently recommended for diagnosis of obstructive sleep apnea and titration of effective continuous positive airway pressure (CPAP). Objective: To test the utility of a diagnostic algorithm in conjunction with ambulatory CPAP titration in initial management of obstructive sleep apnea. Design: A randomized, controlled, open-label trial that compared standard PSG with ambulatory CPAP titration in high-risk patients identified by a diagnostic algorithm. Setting: A tertiary referral sleep disorders program in Vancouver, British Columbia, Canada. Patients: 68 patients with a high pretest probability of moderate to severe obstructive sleep apnea (apnea–hypopnea index [AHI] >15 episodes/h) identified by sequential application of the Epworth Sleepiness Scale (ESS) score, Sleep Apnea Clinical Score, and overnight oximetry. Intervention: Patients were randomly assigned to PSG or ambulatory titration by using a combination of auto-CPAP and overnight oximetry. They were observed for 3 months. Measurements: Apnea–hypopnea index on CPAP, ESS score, quality of life, and CPAP adherence. Results: The PSG and ambulatory groups had similar median BMI (38 kg/m2), age (55 years), ESS score (14 points), and respiratory disturbance index (31 episodes of respiratory disturbance/h). Each episode is determined by a computer algorithm based on analysis of oxygen saturation measured by pulse oximetry. After 3 months, there were no differences in the primary outcome, AHI on CPAP (median, 3.2 vs. 2.5; difference, 0.8/h [95% CI, −0.9 to 2.3]) (P = 0.31), between the PSG and ambulatory groups, or in the secondary outcomes, ESS score, Sleep Apnea Quality of Life Index, and CPAP. Adherence to CPAP therapy was better in the ambulatory group than in the PSG group (median, 5.4 vs. 6.0; difference, −1.12 h/night [CI, −2.0 to 0.2]) (P = 0.021). Conclusions: In the initial management of patients with a high probability of obstructive sleep apnea, PSG confers no advantage over the ambulatory approach in terms of diagnosis and CPAP titration. The ambulatory approach may improve adherence to treatment. When access to PSG is inadequate, the ambulatory approach can be used to expedite management of patients most in need of treatment.
Heart failure with preserved ejection fraction. Diastolic dysfunction, subtle systolic dysfunction, systolic-ventricular and arterial stiffening, or misdiagnosis?
Authors: P STEENDIJK
Journal: Cardiovascular Research (2004)

See article by He et al.  [19]  (pages 72–83) in this issue .

Patients with signs and symptoms of congestive heart failure (CHF) may present with a normal left ventricular (LV) ejection fraction (EF). Epidemiological studies indicate that about half of the CHF patients in the community have a relatively normal or preserved EF (typically defined as EF>50%) [1–3]. This finding appears to be in line with hospital-based studies, but the heterogeneity in patient selection, diagnostic criteria for CHF, and methods for assessment of systolic function makes it difficult to compare these studies [4]. Compared to patients with CHF and depressed EF, patients with CHF and preserved EF are older, are more often women, more frequently have a history of hypertension, and less frequently have coronary artery disease [1–4]. CHF is the most frequent cause of hospitalization in persons 65 years of age or older, and a recent large-scale, population-based study [5] indicates a prevalence for CHF of 4.9% in this age group. Interestingly, only 22% of these CHF patients had overtly impaired LV systolic function (defined as EF<45%). Of note is that the mean age of patients represented in the major CHF treatment trials is typically 59–65, whereas the mean age of patients in the community at the time of first diagnosis of CHF appears to be about 77 [1,6].

It is often assumed that the prognosis of CHF patients is better for those with a preserved EF. This notion is supported by the meta-analysis by Vasan et al. [4] which covers 31 studies on CHF with preserved EF performed between 1970 and 1995. The reported annual mortality rate in the reviewed studies ranged between 1.3% and 17.5%. This wide range is partly related to variation in the patient selection criteria and … 

*Corresponding author. Tel.: +31 71 526 2020; fax: +31 71 526 6809. E-mail address: p.steendijk{at}lumc.nl
A statistical survey of the composition of gallstones in eight countries
Authors: D. J. Sutor, S. E. Wooley
Journal: Gut (1971)

The crystalline composition of gallstones from Australia, England, Germany, India, Kuwait, South Africa, Sweden, and the USA has now been determined by the <i>x</i>-ray powder method. Eleven compounds were identified. The three cholesterols—cholesterol monohydrate, anhydrous cholesterol, and cholesterol II—account for 71% of the total crystalline material in the stones; the calcium carbonates—vaterite, aragonite, and calcite—contribute 15%, and calcium palmitate contributes 6%. Smaller amounts of apatite, sodium chloride, whitlockite, and α-palmitic acid were also found. The composition distribution in each country is significantly different. Gallstones from Germany, Sweden, and Australia are the most similar. Gallstones from England have significantly more carbonate, and stones from South Africa have much less cholesterol and more calcium phosphate and calcium palmitate. Stones from Kuwait have a large amount of calcium palmitate and those from India an excess of calcium phosphate. The composition of stones related to the age and to the sex of a patient shows that although there are no significant differences in composition for patients under and over the age of 50 there are differences in the stone composition related to the patient9s sex. Female patients form much more cholesterol while males form much more calcium palmitate and slightly more calcium carbonate. The differences also exist for female and male patients over and under 50 years of age. A study of the texture and orientation of the crystalline material in the gallstones has shown that anhydrous cholesterol and cholesterol monohydrate can occur as single crystals oriented with respect to the nucleus whereas other stone components are disoriented crystallites.
THE BINDING OF FATTY ACIDS BY SERUM ALBUMIN, A PROTECTIVE GROWTH FACTOR IN BACTERIOLOGICAL MEDIA
Authors: Bernard D. Davis, René J. Dubos
Journal: The Journal of Experimental Medicine (1947)

Serum albumin is a protective bacterial growth factor; by binding traces of fatty acid in the media it permits initiation of growth by the smallest possible inocula of tubercle bacilli. Each molecule of albumin binds 3 to 6 molecules of oleic acid (1 to 2 per cent of the weight of the albumin) tightly enough to prevent bacteriostasis, and 9 molecules of oleic acid in equilibrium with a saturated neutral solution. The property requires undenatured albumin. Crystalline beta-lactoglobulin has a smaller capacity, and a number of other proteins no perceptible capacity to bind oleic acid. The inhibitory effect of the commercial product Tween 80 (polyoxyethylene sorbitan monooleate) on the growth of small inocula of tubercle bacilli in liquid media is caused by its content of unesterified oleic acid (0.6 per cent by weight). Purified Tween 80, freed of this contaminating fatty acid, not only permits growth of small inocula, but protects against small amounts of added oleic acid. The implications of the binding capacity of albumin for its possible physiological significance in the animal body (transport; protection against cytotoxins), and for the structure of the protein, are briefly discussed.
Increased urinary excretion of aquaporin 2 in patients with liver cirrhosis
Authors: P Ivarsen
Journal: Gut (2003)

<b>Background and aim:</b> Water retention is a major clinical problem in patients with liver cirrhosis. Recent research suggests that renal aquaporins may be pathophysiologically involved in this condition. The aim of the present cross sectional study of patients with liver cirrhosis was to determine if 24 hour urinary excretion of renal aquaporin 2 (AQP2) differed from that of healthy control subjects and if such excretion was related to the severity of liver disease and to the patient’s water balance. <b>Results:</b> Twenty four hour urinary excretion of AQP2 and free water clearance were measured in 33 stable cirrhosis patients on usual medication and in eight healthy subjects. AQP2 excretion, quantitated by immunoblotting, was eight times higher in cirrhosis patients than in controls (0.167 (0.270) U/day <i>v</i> 0.021 (0.017); p&lt;0.05). Stratification according to clinical manifestations (Child- Pugh classes) revealed that it increased with the clinical severity of cirrhosis (class A 0.04 (0.04); class B 0.09 (0.16); class C 0.31 (0.35); p&lt;0.05) but was not related to liver function, as measured by galactose elimination capacity. Excretion correlated inversely with free water clearance (rho=−0.57, p&lt;0.01). It was higher in patients with oesophagogastric varices but not in those with ascites. Plasma vasopressin concentrations were not related to AQP2 excretion and there was no relation to dose or type of diuretic treatment. <b>Conclusions:</b> Urinary AQP2 excretion was increased in patients with cirrhosis. Moreover, urinary AQP2 excretion increased with severity of cirrhosis in parallel with impairment of free water clearance. This suggests a functional association between increased AQP2 excretion and increased renal reabsorption of water in cirrhosis.
The Intersectin 2 Adaptor Links Wiskott Aldrich Syndrome Protein (WASp)-mediated Actin Polymerization to T Cell Antigen Receptor Endocytosis
Authors: Mary K.H. McGavin, Karen Badour, Lynne A. Hardy, Terrance J. Kubiseski, Jinyi Zhang, Katherine A. Siminovitch
Journal: The Journal of Experimental Medicine (2001)

Induction of T cell antigen receptor (TCR) endocytosis has a significant impact on TCR signaling and T cell behavior, but the molecular interactions coordinating internalization of the activated TCR are poorly understood. Previously we have shown that TCR endocytosis is regulated by the Wiskott Aldrich Syndrome protein (WASp), a cytosolic effector which, upon interaction with the cdc42 Rho GTPase, couples TCR engagement to Arp 2/3 complex-mediated actin polymerization. Here we report that WASp associates in T cells with intersectin 2, an endocytic adaptor containing multiple domains including a Dbl homology (DH) domain with the potential to activate Rho GTPases. Intersectin 2 association with WASp increases after TCR engagement, and its overexpression in Cos-7 cells induces WASp translocation to endocytic vesicles within which intersectin 2 colocalizes with both WASp and cdc42. Intersectin 2, but not a DH domain-deleted (ΔDH) form of intersectin 2, and stimulation via the TCR also trigger the activation of cdc42. Induction of TCR internalization is also augmented by intersectin 2 and severely impaired by latrunculin B treatment. Thus, intersection 2 appears to function cooperatively with WASp and cdc42 to link the clathrin endocytic machinery to WASp-mediated actin polymerization and ultimately to occupancy-induced TCR endocytosis.
Variants on a Theme: A Biomarker of Crizotinib Response in ALK-Positive Non–Small Cell Lung Cancer?
Authors: Adam S. Crystal, Alice T. Shaw
Journal: Clinical Cancer Research (2012)

Anaplastic lymphoma kinase (ALK) gene rearrangements are found in approximately 5% of non-small cell lung carcinoma patients and confer sensitivity to ALK inhibitors such as crizotinib. The particular ALK fusion expressed may have an impact on protein stability and sensitivity to crizotinib, and this may underlie the heterogeneity in responses observed in the clinic.
Propranolol and the Prevention of Post-Traumatic Stress Disorder: Is it Wrong to Erase the “Sting” of Bad Memories?
Authors: Michael Henry, Jennifer R. Fishman, Stuart J. Youngner
Journal: The American Journal of Bioethics (2007)

The National Institute of Mental Health (Bethesda, MD) reports that approximately 5.2 million Americans experience post-traumatic stress disorder (PTSD) each year. PTSD can be severely debilitating and diminish quality of life for patients and those who care for them. Studies have indicated that propranolol, a beta-blocker, reduces consolidation of emotional memory. When administered immediately after a psychic trauma, it is efficacious as a prophylactic for PTSD. Use of such memory-altering drugs raises important ethical concerns, including some futuristic dystopias put forth by the President's Council on Bioethics. We think that adequate informed consent should facilitate ethical research using propranolol and, if it proves efficacious, routine treatment. Clinical evidence from studies should certainly continue to evaluate realistic concerns about possible ill effects of diminishing memory. If memory-attenuating drugs prove effective, we believe that the most immediate social concern is the over-medicalization of bad memories, and its subsequent exploitation by the pharmaceutical industry.