tbuckley/cabot-search huggingface dataset:
Label-Free Neurosurgical Pathology with Stimulated Raman Imaging
Authors: Fa-Ke Lu, David Calligaris, Olutayo I. Olubiyi, Isaiah Norton, Wenlong Yang, Sandro Santagata, X. Sunney Xie, Alexandra J. Golby, Nathalie Y.R. Agar
Journal: Cancer Research (2016)

Abstract The goal of brain tumor surgery is to maximize tumor removal without injuring critical brain structures. Achieving this goal is challenging as it can be difficult to distinguish tumor from nontumor tissue. While standard histopathology provides information that could assist tumor delineation, it cannot be performed iteratively during surgery as freezing, sectioning, and staining of the tissue require too much time. Stimulated Raman scattering (SRS) microscopy is a powerful label-free chemical imaging technology that enables rapid mapping of lipids and proteins within a fresh specimen. This information can be rendered into pathology-like images. Although this approach has been used to assess the density of glioma cells in murine orthotopic xenografts models and human brain tumors, tissue heterogeneity in clinical brain tumors has not yet been fully evaluated with SRS imaging. Here we profile 41 specimens resected from 12 patients with a range of brain tumors. By evaluating large-scale stimulated Raman imaging data and correlating this data with current clinical gold standard of histopathology for 4,422 fields of view, we capture many essential diagnostic hallmarks for glioma classification. Notably, in fresh tumor samples, we observe additional features, not seen by conventional methods, including extensive lipid droplets within glioma cells, collagen deposition in gliosarcoma, and irregularity and disruption of myelinated fibers in areas infiltrated by oligodendroglioma cells. The data are freely available in a public resource to foster diagnostic training and to permit additional interrogation. Our work establishes the methodology and provides a significant collection of reference images for label-free neurosurgical pathology. Cancer Res; 76(12); 3451–62. ©2016 AACR.
Unfair comparison
Authors: Iain S Fraser
Journal: BMJ (2007)

The Euro Health Consumer Index 2007 is being cited as evidence that the Bismark system ?delivers better value? than the Beveridge system.1 One might, however, pause to consider World Health Statistics 2007 from the World Health Organization (www.who.int) as shown in the table​table.





Public healthcare statistics from the WHO



Surely it is premature to draw conclusions on the merits of one system over another when the playing field is far from level?
Sweating and Congestive Heart Failure
Authors: Clarence L. Morgan, Alexander S. Nadas
Journal: New England Journal of Medicine (1963)

EXCESSIVE perspiration has been noted for a number of years to be one of the signs and symptoms of congestive heart failure in this clinic. As a matter of fact, it is so frequent that our standard cardiac clinic sheet lists increased sweating as one of the symptoms to be checked on the first visit. On the hospital ward it is particularly striking to see the moist, sweat-covered forehead of infants in a cool room or a cool oxygen tent. Aside from cystic fibrosis,1 2 3 sweating has received little comment in the literature, probably because of difficulty in accurately measuring sweating . . .
Ph Ii Study of Bez235 in Patients with Advanced Pancreatic Neuroendocrine Tumors (Pnet) After Mtor Inhibitor Therapy Failure: Stage I Interim Results
Authors: N. Fazio, R. Buzzoni, E. Baudin, L. Antonuzzo, R. Hubner, H. Lahner, W.W. De Herder, M. Raderer, A. Teule, J. Capdevila, S. Libutti, M. Kulke, M. Shah, D. Dey, S. Turri, P. Aimone, C. Verslype
Journal: Annals of Oncology (2014)
120P: Neoadjuvant chemotherapy followed by either continuous hyper-fractionated accelerated radiation therapy week-end less or conventional chemo-radiotherapy in locally advanced non small cell lung cancer
Authors: R.K. Sinwer, H.S. Kumar, M. Paramanandhan, R. Purohit, N. Sharma, S.N. Sharma
Journal: Journal of Thoracic Oncology (2016)
M4 Association of descriptors of breathlessness with diagnosis, self-reported severity of breathlessness and self-reported distress due to breathlessness in patients with advanced chronic obstructive pulmonary disease or cancer: Abstract M4 Table 1
Authors: S Chowienczyk, S Javadzadeh, S Booth, M Farquhar
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Verbal descriptors are important in understanding patients’ experience of breathlessness. The selection of breathlessness descriptors may depend on the severity of breathlessness.<sup>1</sup> Our objective was to examine the association between selection of the breathlessness descriptors devised by Simon <i>et al</i>. with diagnosis, self-reported severity of breathlessness and self-reported distress due to breathlessness.<sup>2</sup> <h3>Methods</h3> We studied 132 patients grouped according to their diagnosis advanced COPD (n = 69) or advanced cancer (n = 63), self-reported severity of breathlessness: mild breathlessness (Numerical rating scale (NRS) ≤3, n = 53), moderate breathlessness (4≤NRS≥6, n = 59) or severe breathlessness (NRS ≥7, n = 20), and distress due to breathlessness: mild distress (NRS ≤3, n = 31), moderate distress (4≤NRS≥6, n = 44) or severe distress (NRS ≥7, n = 57). Patients selected three breathlessness descriptors. The relationship between descriptors selected and patient groups was evaluated by cluster analysis. <h3>Results</h3> Cluster analysis identified six clusters of descriptors: ‘breathing restrictions’, ‘enough air’, ‘out of breath’, ‘air hunger’, ‘effort’ and ‘chest tightness’. Different combinations of clusters were associated with each diagnostic group. The association of clusters with patient groups differed depending on their severity of breathlessness and their distress due to breathlessness. The ‘air hunger’ cluster was associated with patients with moderate or severe breathlessness, the ‘chest tightness’ cluster was associated with patients with mild breathlessness. The ‘air hunger’ cluster was associated with patients with severe distress due to breathlessness. <h3>Conclusions</h3> The relationship between clusters and diagnosis is not robust enough to use the descriptors to identify the primary cause of breathlessness. Further work exploring how use of breathlessness descriptors reflects the severity of breathlessness and distress due to breathlessness could enable the descriptors to evaluate patient status and target interventions. <h3>References</h3> 1 Von Leupoldt A, Balewski S, Petersen S, <i>et al</i>. Verbal descriptors of dyspnea in patients with COPD at different intensity levels of dyspnea. <i>Chest</i> 2007;<b>132</b>:141–147 2 Simon PM, Schwartzstein RM, Weiss JW, <i>et al</i>. Distinguishable sensations of breathlessness induced in normal volunteers. <i>Am Rev Respir Dis</i>. 1989;<b>140</b>:1021–1027
Flavopiridol, fludarabine and rituximab (FFR) is an active regimen in indolent B-cell lymphoproliferative disorders and mantle cell lymphoma (MCL)
Authors: T. S. Lin, B. Fischer, M. E. Moran, R. S. Shank, E. Kraut, P. Porcu, S. S. Farag, K. A. Blum, A. D. Colevas, M. R. Grever, J. C. Byrd
Journal: Journal of Clinical Oncology (2006)

7599 Background: The cyclin-dependent kinase inhibitor flavopiridol is active in MCL and chronic lymphocytic leukemia (CLL) when given by 1-hr IV bolus dosing. Flavopiridol induces apoptosis independent of p53 and may eliminate tumor cells resistant to fludarabine and rituximab. Methods: We performed a phase I dose escalation study of flavopiridol, fludarabine and rituximab (FFR) in patients (pts) with MCL, CLL and indolent B-cell non-Hodgkin’s lymphoma (NHL). Pts received fludarabine 25 mg/m 2 IV day 1–5 and rituximab 375 mg/m 2 day 1 every 28 days for up to 6 cycles. Flavopiridol was given 50 mg/m 2 by 1-hr IV bolus day 1 (cohort 1), day 1–2 (cohort 2), or day 1–3 (cohort 3) of each cycle. Growth factor support was prohibited. Results: Twenty-one pts were enrolled and are evaluable for toxicity and response. Median age was 62 years (range, 43–81); 8 pts had CLL, 5 MCL, 4 follicular NHL (FL), and 4 other low-grade NHL. Nine pts had received 1–2 prior therapies; 12 pts were previously untreated. CLL pts were Rai stage III/IV (5) or required treatment for stage I/II disease (3). NHL pts had stage III/IV (10) or progressive stage II disease (3). Dose limiting toxicity (DLT) was not observed in 3 pts in cohort 1. Two of 6 pts in cohort 2 developed DLT (grade 3 seizures; grade 3 renal failure due to nausea and diarrhea). Twelve additional pts were enrolled at the cohort 1 dose level, to define toxicity and efficacy. Pts received a median of 4 cycles (range 1–6), and 9 of 21 pts completed 6 cycles. Therapy was stopped early due to cytopenias (7), infection (2), DLT (2) or progressive disease (1). Response was graded by NCI 96 (CLL) or IWG (NHL) criteria. Overall response rate was 90%, and 14 pts achieved CR (67%). Six pts relapsed a median of 7.5 months (range 4–18) after finishing therapy; 13 pts remain in remission a median of 13.5 months (range 4–25) after therapy. All 9 MCL/FL pts responded (8 CR, 1 PR), and 8 pts remain in remission a median of 17 months (range 6–25) after therapy. Conclusions: FFR showed significant clinical activity in a small group of pts, but cytopenias limited therapy. We are currently studying a modified FFR regimen using a more active flavopiridol schedule (30-min IV bolus followed by 4-hr IV infusion) and allowing the use of prophylactic filgrastim. [Table: see text]
The Diagnosis of Gout
Authors: Joel C. Goldthwait, Carrol F. Butler, J. Sydney Stillman
Journal: New England Journal of Medicine (1958)

THROUGH the years it has been emphasized1 , 2 that gout is a disease often overlooked by the physician although in the majority of cases the clinical picture is pathognomonic. Those whose interests lead them to see patients afflicted by bone and joint disease are not infrequently faced by a routine serum uric acid determination that returns a high level suggestive of gout whereas the clinical picture is not consistent with this diagnosis. It is our purpose in the presentation that follows to describe the experience at the Robert Breck Brigham Hospital with this problem in differential diagnosis. The approach has been . . .
SP0118 People Movers: How You Can Influence and Effectively Implement Change
Authors: C. Brand
Journal: Annals of the Rheumatic Diseases (2015)

The worldwide challenge of preventing and managing chronic conditions, including musculoskeletal conditions such as osteoarthritis in the 21st Century is increasingly recognized. As a community and as individuals we must face and respond to an increasing incidence and prevalence of chronic conditions as well as a rise in predisposing or aggravating lifestyle risk factors, notably physical inactivity and overweight/obese body status. The inadequacy of traditional medical models of care for management of chronic conditions has seen a shift towards new interdisciplinary, shared care models but we are struggling to effectively implement and appropriately evaluate these programs to demonstrate cost-effectiveness and sustainability. Implementing complex health service interventions, such as new models of care, requires all stakeholders, including amongst others; health managers, clinicians and consumers and their families to make changes to the way they perform their usual daily activities. We know a little about the various barriers to change at different levels of the health system and for different stakeholders, but how much do we understand about enabling factors especially motivation and how to influence these factors? In this presentation I will focus on issues associated with "change"; the theories that underpin our understanding about change and the strategies that have demonstrable effectiveness in promoting and sustaining change behaviours. I will also discuss the opportunities we have to learn from innovative application of online technologies using fun theory and gamification, in order to better support change and thus improve chronic condition health outcomes. <h3>Disclosure of Interest</h3> None declared
Metformin-Induced Hemolysis with Jaundice
Authors: Koan-Day Lin, Jen-Der Lin, Jyuhn-Huarng Juang
Journal: New England Journal of Medicine (1998)

To the Editor: Metformin is an effective treatment for many patients with type 2 diabetes mellitus. Although it lowers serum vitamin B12 concentrations, it does not cause anemia.1 We describe a patient with metformin-induced hemolysis and jaundice. A 46-year-old man presented at our hospital on March 31, 1998, with a one-week history of polydipsia and polyuria. The physical examination was normal except for the presence of obesity (body-mass index [the weight in kilograms divided by the square of the height in meters], 29.4). Hyperglycemia was documented, and the patient was treated by dietary restriction and 500 mg of metformin . . .
Depletion of Erythrocyte Phosphoribosylpyrophosphate in Man
Authors: Irving H. Fox, James B. Wyngaarden, William N. Kelley
Journal: New England Journal of Medicine (1970)

Allopurinol, a potent inhibitor of xanthine oxidase, is widely used for the treatment of hyperuricemia. When this drug was given to nine patients with gout, the concentration of phosphoribosylpyrophosphate (PRPP) in red cells was reduced significantly (p<0.01). Studies in vivo and in vitro showed that this depletion of PRPP results from the enzymatic conversion of allopurinol to allopurinol ribonucleotide, a process that consumes PRPP. The findings that allopurinol depletes PRPP and is apparently converted to its ribonucleotide in vivo suggest that this widely used drug may have a variety of biochemical effects in addition to xanthine oxidase inhibition. The observed changes provide several likely mechanisms to account for the previously documented inhibitory effect of allopurinol on purine synthesis de novo.
Treatment with Azacitidine of Patients with End-Stage β-Thalassemia
Authors: Christopher H. Lowrey, Arthur W. Nienhuis
Journal: New England Journal of Medicine (1993)

Regular erythrocyte transfusions form the cornerstone of treatment for patients with severe β-thalassemia. Despite the use of iron-chelation therapy, fatal iron overload develops in many patients, even when they are under supervision and taking part in studies designed to test the effectiveness of intense chelation1,2. Another potential consequence of long-term transfusions is the development of antierythrocyte antibodies, making effective transfusion difficult or, in rare cases, impossible3–6. A potential alternative to transfusion is the use of the nucleoside analogue azacitidine to stimulate transcription of the fetal globin genes by pharmacologic means and thus lead to more effective . . .
Deficiency of Galactosylhydroxylysyl Glucosyltransferase, an Enzyme of Collagen Synthesis, in a Family with Dominant Epidermolysis Bullosa Simplex
Authors: Eeva-Riitta Savolainen, Matti Kero, Taina Pihlajaniemi, Kari I. Kivirikko
Journal: New England Journal of Medicine (1981)

Members of a family with dominant epidermolysis bullosa simplex were found to have a deficiency of galactosylhydroxylysyl glucosyltransferase (GGT), an enzyme catalyzing the glucosylation of galactosylhydroxylysyl residues in the biosynthesis of collagen. The enzyme's activity was low in serum, skin tissue, and cultured skin fibroblasts, although no abnormality was found in three other intracellular enzymes of collagen biosynthesis. Mixtures of serum samples from patients and healthy controls gave the expected GGT activity, indicating that the low values were not due to inhibitors. GGT deficiency was accompanied by decreased product formation in vivo, as shown by a markedly decreased urinary excretion of glucosylgalactosylhydroxylysine. Six of 12 affected members had definite GGT deficiency, and five had some evidence suggestive of this abnormality; 13 of 15 unaffected members had no such manifestations. No similar GGT deficiency was found in three other families with the same disease. We conclude that GGT deficiency may be etiologically related to this disease in some families, but that different defects must be the cause in other cases.
Serologic Evidence of Infection with Eaton Agent in Lower Respiratory Illness in Childhood
Authors: R. M. Chanock, M. K. Cook, H. H. Fox, R. H. Parrott, R. J. Huebner
Journal: New England Journal of Medicine (1960)

THE agent isolated in cotton rats, hamsters or embryonated hen's eggs by Eaton et al.1 2 3 from patients with cold-agglutinin-positive atypical pneumonia has been the subject of considerable controversy. This agent could be propagated in embryonated eggs and produced pneumonic lesions in hamsters and cotton rats after intranasal inoculation. The results of neutralization tests in hamsters or cotton rats that suggested the development of antibody to this agent during convalescence from atypical pneumonia have not been accepted by certain workers since the challenge inoculum did not produce pneumonitis in all inoculated animals. In addition, the question of latent agents in cotton . . .
Increased Serum Thyroid Hormone Binding and Decreased Free Hormone in Chronic Active Liver Disease
Authors: George C. Schussler, Fenton Schaffner, Felice Korn
Journal: New England Journal of Medicine (1978)

To determine whether chronic inflammatory disease of the liver increases serum thyroid hormone binding, we measured tri-iodothyronine resin binding ratios in nine patient with primary biliary cirrhosis and in nine with chronic active hepatitis. In each group, the average binding ratio was about 50 per cent higher than in control subjects. Thyroxinebinding globulin, measured by immunoassay in three patients, was elevated. Although average total thyroxine and tri-iodothyronine were increased slightly, the corresponding free hormone concentrations were lower than controls, probably because of decreased thyroid function associated with the high incidence of autoimmune thyroiditis in nonalcoholic (autoimmune) liver disease. Thyroid autoantibodies were found in 13 patients. Impaired hepatic thyroxine-to -tri-iodothyronine conversion may have contributed to the low free tri-iodothyronine. Thyrotropin was elevated in four patients. Because of increased serum thyroid hormone binding in these patients total thyroxine and tri-iodothyronine concentration can be normal despite hypothyroidism.
P14 Pirfenidone is efficacious in patients with idiopathic pulmonary fibrosis (IPF) with more preserved lung function
Authors: PW Noble, WZ Bradford, U Costabel, I Glaspole, MK Glassberg, E Gorina, D Kardatzke, L Lancaster, DJ Lederer, SD Nathan, C Pereira, D Spirig, JJ Swigris, D Valeyre, C Albera
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> IPF is a progressive, irreversible and fatal disease. Early treatment initiation when lung function is relatively preserved may have beneficial outcomes; however, published data to support this hypothesis are lacking. We investigated the efficacy of pirfenidone at 12 months in patients stratified by lung function using forced vital capacity (FVC) or GAP stage. <h3>Methods</h3> Efficacy outcomes (FVC, 6-minute walk distance [6MWD] and dyspnea [UCSD SOBQ]) were analysed at 12 months in patients randomised to pirfenidone 2403 mg/d or placebo in the pooled CAPACITY/ASCEND population (N = 1247), stratified by baseline FVC (≥80%, &lt;80%) and GAP stage (GAP I, GAP II-III). Treatment-by-subgroup interaction was tested based on a rank ANCOVA model. The factors in the model included study, region, treatment, subgroup and treatment-by-subgroup interaction term. <h3>Results</h3> Demographic characteristics were similar across all four groups. In the placebo arm, disease progression as measured by FVC occurred with comparable frequency in patients with FVC ≥80% and FVC &lt;80%, as well as in patients with GAP I and GAP II-III stage. A higher proportion of placebo patients with FVC &lt;80% and GAP II-III stage had a ≥50-m decline in 6MWD or death or a ≥20-point change in the UCSD SOBQ total score. Pirfenidone treatment reduced the proportion of patients experiencing a ≥10% FVC decline or death and increased the proportion of patients with no FVC decline in all subgroups. Pirfenidone also reduced the proportion of patients with ≥50-m decline in the 6MWD or death and increased the proportion of patients with no 6MWD decline in all subgroups. The magnitude of treatment effect in patients with less <i>vs </i>more preserved lung function was comparable, with no significant treatment-by subgroup interaction (Figure 1). <h3>Conclusions</h3> In the placebo population, clinically significant disease progression occurs in subgroups with more and less preserved lung function at baseline, underlying the need for early intervention. The magnitude of pirfenidone treatment effect on functional measures was comparable in these subgroups of patients (FVC &lt;80% <i>vs </i>FVC ≥80% or GAP I vs GAP II-III stage), supporting the initiation of treatment soon after diagnosis, when pulmonary function is relatively preserved.
Attention Deficit-Hyperactivity Disorder in People with Generalized Resistance to Thyroid Hormone
Authors: Peter Hauser, Alan J. Zametkin, Pedro Martinez, Benedetto Vitiello, John A. Matochik, James A. Mixson, Bruce D. Weintraub
Journal: New England Journal of Medicine (1993)

Attention deficit-hyperactivity disorder is a well-recognized psychiatric disorder of childhood. Its cause is unknown, but there is evidence of a familial predisposition. Symptoms suggestive of this disorder have been reported in subjects with generalized resistance to thyroid hormone, a disease caused by mutations in the thyroid receptor-beta gene and characterized by reduced responsiveness of peripheral and pituitary tissues to the actions of thyroid hormone. We systematically evaluated the presence and severity of attention deficit-hyperactivity disorder in 18 families with a history of generalized resistance to thyroid hormone.We studied 49 affected and 55 unaffected family members; 52 were adults, and 52 were children. All subjects were evaluated with structured psychiatric questionnaires by interviewers who were unaware of the medical diagnosis. The number of symptoms of attention deficit-hyperactivity disorder was calculated for each subject.Among the adults, 11 of 22 subjects with generalized resistance to thyroid hormone (50 percent) and 2 of 30 unaffected subjects (7 percent) had met the criteria for attention deficit-hyperactivity disorder as children (P < 0.001). Among the children, 19 of 27 subjects resistant to thyroid hormone (70 percent) and 5 of 25 unaffected subjects (20 percent) met the criteria for the disorder (P < 0.001). The odds of having attention deficit-hyperactivity disorder were 3.2 times higher for affected male subjects than for affected female subjects and were 2.7 times higher for unaffected male subjects than for unaffected female subjects. The mean symptom score was 2.5 times higher in the affected group than in the unaffected group (7.0 vs. 2.8, P < 0.001). The frequency of other psychiatric diagnoses was similar in the two groups.In our study sample, attention deficit-hyperactivity disorder is strongly associated with generalized resistance to thyroid hormone.