tbuckley/cabot-search huggingface dataset:
When is a prognostic factor useful? A guide for the perplexed.
Authors: M N Levine, G P Browman, M Gent, R Roberts, M Goodyear
Journal: Journal of Clinical Oncology (1991)

Traditionally, a number of variables have been used to predict outcome in patients with early-stage breast cancer. These tests are simple to perform and relatively inexpensive. Recently, a number of new factors, eg, tumor proliferative index, nuclear DNA content, and amplification or overexpression of growth-promoting genes or oncogenes have been identified as potential predictors of outcome in patients with breast cancer. There is now increasing pressure to introduce such tests into routine clinical practice. How does a clinical practitioner identify which test, or group of tests, best predicts adverse outcome and whether any more clinically useful information is provided than with the use of more traditional factors alone? The aim of a prognostic test in breast cancer is to predict which patients are destined to develop a recurrence of cancer and those who are not. The prognostic usefulness of a test can be expressed in terms of relative risk (RR), which is the ratio of the risk of breast cancer recurrence in patients who test positive to the risk in those who test negative. Methodologic guidelines that should be satisfied by a study evaluating the predictive ability of a test include the following: (1) Was an inception cohort assembled? (2) Was the referral pattern described? (3) Were laboratory and clinical outcomes assessed in a blinded fashion? (4) Was complete follow-up achieved? (5) Was adjustment for extraneous prognostic factors carried out? (6) Were appropriate statistical methods used? An approach is suggested to help the clinician choose the test, or combination of tests, likely to discriminate between "high-" and "low-risk" patients in his/her own practice. The decision regarding what particular threshold value (risk) defined by a prognostic test (or series of tests) warrants adjuvant therapy for an individual patient is a complex one but should be based on a clear presentation of the risks and benefits to the patient.
Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha
Authors: Amy V. Jones, Richard T. Silver, Katherine Waghorn, Claire Curtis, Sebastian Kreil, Katerina Zoi, Andreas Hochhaus, David Oscier, Georgia Metzgeroth, Eva Lengfelder, Andreas Reiter, Andrew J. Chase, Nicholas C. P. Cross
Journal: Blood (2005)
Cyclin and cyclin-dependent kinase expression in the remnant glomerulus.
Authors: S J Shankland, P Hamel, J W Scholey
Journal: Journal of the American Society of Nephrology (1997)

Recent studies suggest that subtotal renal ablation is associated with an early phase of mesangial cell proliferation. Because the mechanism(s) responsible for this response have not been elucidated, the study presented here sought to determine if changes in expression of positive cell cycle regulators, including pRb, cyclin E, and cdk2, occurred in the glomerulus during the early period of compensatory renal hypertrophy that follows 5/6 renal ablation. A first group of rats underwent sham operation and served as the control group. A second group of rats underwent 5/6 renal ablation. Ninety-six hours after subtotal ablation, protein was extracted from sieved glomeruli for Western blot analysis of proliferating cell nuclear antigen (PCNA) and retinoblastoma protein expression (pRb). RNA was extracted from sieved glomeruli for Northern blot analysis of cyclin E and cdk2 mRNA levels, and renal cortical tissue was subjected to immunohistochemical analysis of PCNA. On average, one PCNA-positive nucleus was present every 22 glomerular profiles in normal rats. The number of PCNA-positive nuclei increased fivefold in glomeruli, 96 h after renal ablation (P < 0.05). pRb was present only in the unphosphorylated state in normal glomeruli, but the increase in PCNA was accompanied by the appearance of phosphorylated pRb in remnant glomeruli. mRNA levels for cyclin E increased twofold in remnant glomeruli, whereas mRNA levels for cdk2 were unchanged. It was concluded that renal ablation leads to cell cycle progression in the glomerulus and an increase in the G1 cyclin, cyclin E, is associated with the appearance of phosphorylated retinoblastoma protein.
Altered Right Atrial Excitation and Propagation in Connexin40 Knockout Mice
Authors: Suveer Bagwe, Omer Berenfeld, Dhananjay Vaidya, Gregory E. Morley, José Jalife
Journal: Circulation (2005)

Intercellular coupling via connexin40 (Cx40) gap junction channels is an important determinant of impulse propagation in the atria.We studied the role of Cx40 in intra-atrial excitation and propagation in wild-type (Cx40(+/+)) and knockout (Cx40(-/-)) mice using high-resolution, dual-wavelength optical mapping. On ECG, the P wave was significantly prolonged in Cx40(-/-) mice (13.4+/-0.5 versus 11.4+/-0.3 ms in Cx40(+/+)). In Cx40(+/+) hearts, spontaneous right atrial (RA) activation showed a focal breakthrough at the junction of the right superior vena cava, sulcus terminalis, and RA free wall, corresponding to the location of the sinoatrial node. In contrast, Cx40(-/-) hearts displayed ectopic breakthrough sites at the base of the sulcus terminalis, RA free wall, and right superior vena cava. Progressive ablation of such sites in 4 Cx40(-/-) mice resulted in ectopic focus migration and cycle length prolongation. In all Cx40(-/-) hearts the focus ultimately shifted to the sinoatrial node at a very prolonged cycle length (initial ectopic cycle length, 182+/-20 ms; postablation sinus cycle length, 387+/-44 ms). In a second group of experiments, epicardial pacing at 10 Hz revealed slower conduction in the RA free wall of 5 Cx40(-/-) hearts than in 5 Cx40(+/+) hearts (0.61+/-0.07 versus 0.94+/-0.07 m/s; P<0.05). Dominant frequency analysis in Cx40(-/-) RA demonstrated significant reduction in the area of 1:1 conduction at 16 Hz (40+/-10% versus 69+/-5% in Cx40(+/+)) and 25 Hz (36+/-11% versus 65+/-9% in Cx40(+/+)).This is the first demonstration of intra-atrial block, ectopic rhythms, and altered atrial propagation in the RA of Cx40(-/-) mice.
FunSeq2: a framework for prioritizing noncoding regulatory variants in cancer
Authors: Yao Fu, Zhu Liu, Shaoke Lou, Jason Bedford, Xinmeng Jasmine Mu, Kevin Y Yip, Ekta Khurana, Mark Gerstein
Journal: Genome biology (2014)

Abstract Identification of noncoding drivers from thousands of somatic alterations in a typical tumor is a difficult and unsolved problem. We report a computational framework, FunSeq2, to annotate and prioritize these mutations. The framework combines an adjustable data context integrating large-scale genomics and cancer resources with a streamlined variant-prioritization pipeline. The pipeline has a weighted scoring system combining: inter- and intra-species conservation; loss- and gain-of-function events for transcription-factor binding; enhancer-gene linkages and network centrality; and per-element recurrence across samples. We further highlight putative drivers with information specific to a particular sample, such as differential expression. FunSeq2 is available from funseq2.gersteinlab.org.
Microbiology of Severe Aspiration Pneumonia in Institutionalized Elderly
Authors: Ali A. El-Solh, Celestino Pietrantoni, Abid Bhat, Alan T. Aquilina, Mifue Okada, Vikas Grover, Nancy Gifford
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

We sought to investigate prospectively the microbial etiology and prognostic indicators of 95 institutionalized elders with severe aspiration pneumonia, and to investigate its relation to oral hygiene in using quantitative bronchial sampling. Data collection included demographic information, Activity of Daily Living, Plaque Index, antimicrobial therapy, and outcome. Out of the 67 pathogens identified, Gram-negative enteric bacilli were the predominant organisms isolated (49%), followed by anaerobic bacteria (16%), and Staphylococcus aureus (12%). The most commonly encountered anaerobes were Prevotella and Fusobacterium species. Aerobic Gram-negative bacilli were recovered in conjunction with 55% of anaerobic isolates. The Plaque Index did not differ significantly between the aerobic (2.2 ± 0.4) and the anaerobic group (2.3 ± 0.3). Functional status was the only determinant of the presence of anaerobic bacteria. Although seven cases with anaerobic isolates received initially inadequate antimicrobial therapy, six had effective clinical response. The crude mortality was 33% for the aerobic and 36% for the anaerobic group (p = 0.9). Stepwise multivariate analysis identified hypoalbuminemia (p < 0.001) and the burden of comorbid diseases (p < 0.001) as independent risk factors of poor outcome. In view of the rising resistance to antimicrobial agents, the importance of adding anaerobic coverage for aspiration pneumonia in institutionalized elders needs to be reexamined.
High-Dose Methotrexate-Induced Renal Dysfunction: Is Glucarpidase Necessary for Rescue?
Authors: Paul A. Meyers, Carlos Flombaum
Journal: Journal of Clinical Oncology (2011)

TO THEEDITOR: Widemann et al 1 report the use of glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction. When patients develop delayed excretion of methotrexate and impaired renal function after the administration of high-dose methotrexate there are two equally important imperatives. First, we must protect the patients from the potential toxicity of prolonged exposure to the antifolate drug methotrexate. Potential toxicities include myelosuppression, mucositis, and hepatoxicity, and can be lethal. The second imperative is to have the patient’s renal function return to normal to allow continuation of the chemotherapy needed to treat the underlying malignancy. The authors performed an analysis to determine which factors predicted greater than or equal to grade 4 toxicity. They noted that inappropriate increase in leucovorin predicted perfectly for development of greater than or equal to grade 4 toxicity and therefore could not be included in their multiple factor logistic regression analysis. We have reported our experience treating patients who have delayed methotrexate excretion and renal failure after high-dose methotrexate administration using high-dose leucovorin as the sole form of rescue. 2 All patients in our experience were salvaged. None of our patients died. The authors report that the median time to recovery of renal function for their cohort was 22 days. Our experience, albeit considerably smaller, achieved at least as good a time to recovery of normal renal function. One possible interpretation of the results that the authors report is that glucarpidase was not an essential component of rescue for patients experiencing high-dose methotrexate-related renal dysfunction and that similar results could have been achieved with the use of high-doses of leucovorin alone. Glucarpidase is unquestionably an excellent way to lower the plasma methotrexate concentration. This effect, however, has no impact on intracellular concentrations of methotrexate or on renal function. Protection of cells from intracellular methotrexate still requires the administration of high-doses of leucovorin and renal recovery appears to take place independently of glucarpidase administration. The authors’ conclusion that early intervention with the combination of leucovorin and glucarpidase is highly effective in patients who develop high-dose methotrexate-related renal dysfunction may be true but the authors should consider the possibility that similar results could be achieved with leucovorin alone.
Chronic pancreatitis: a cause of cholestasis.
Authors: J Scott, J A Summerfield, E Elias, R Dick, S Sherlock
Journal: Gut (1977)

The bile ducts were visualised using endoscopic retrograde cholangiopancreatography (ERCP), percutaneous or intravenous cholangiography in 38 patients with non-gallstone chronic pancreatitis. Stenosis of the intrapancreatic portion of the distal common bile duct was demonstrated in 11 patients. Ten of the 11 developed transient cholestasis during exacerbations of their chronic pancreatitis. In six cholestasis eventually persisted requiring surgical relief. Secondary biliary cirrhosis was present in one patient. No evidence of pancreatic carcinoma was found in the patients explored surgically. Ten of the patients are alive more than one year after diagnosis.Chronic pancreatitis was of alcoholic aetiology in 10 of the patients with biliary stenosis. Cholestasis and biliary stricture are common but poorly recognised complications of non-gallstone chronic pancreatitis, especially when pancreatitis is severe and due to alcohol.
Intrahepatic cholestasis of pregnancy as an indicator of liver and biliary diseases: A population-based study
Authors: Anne Ropponen, Reijo Sund, Seija Riikonen, Olavi Ylikorkala, Kristiina Aittomäki
Journal: Hepatology (2006)

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder, thought to be specific for pregnancy and to spontaneously resolve after delivery. Increased rates of gallstone formation and hepatitis C have previously been associated with ICP. However, there are no longitudinal studies to determine its significance as an indicator of subsequent liver or biliary diseases. In this retrospective cohort study with cases and controls we assessed the risk of liver and biliary diseases in 21,008 women, 10,504 with a history of ICP during the years 1972-2000 (cases) and 10,504 with a normal pregnancy (controls). Cases and controls were matched for age, time of delivery, and place of delivery. The diagnoses of liver and biliary disease were traced from the Finnish Hospital Discharge Register with an almost 100% coverage. Several liver and biliary diseases were found to have a significantly higher incidence in patients with ICP than in controls. The rate ratio for hepatitis C was 3.5 (CI 1.6-7.6; P < .001), for nonalcoholic liver cirrhosis 8.2 (CI 1.9-35.5; P < .05), for gallstones and cholecystitis 3.7 (CI 3.2-4.2; P < .001) and for nonalcoholic pancreatitis 3.2 (CI 1.7-5.7; P < .001). In conclusion, there is an association of ICP with several liver and biliary diseases. Some patients with ICP are at risk of the subsequent development of cirrhosis and other severe chronic diseases. Contrary to what has been previously thought, follow-up may need to be considered for these patients.
Legionella longbeachae Species Nova, Another Etiologic Agent of Human Pneumonia
Authors: ROGER M. McKINNEY
Journal: Annals of Internal Medicine (1981)

A new species of bacteria that is an etiologic agent of human pneumonia has been isolated and characterized. Clinical symptoms of infection with this organism are not readily distinguishable from those caused by Legionella pneumophila infection. The organism was isolated from respiratory tract specimens from four patients. Two cases of infection apparently originated in California and one in Georgia, and a fourth was of unknown geographic origin. The name Legionella longbeachae species nova is proposed for this organism. The type strain of L. longbeachae is Long Beach 4 (= American Type Culture Collection 33462).
The prevalence of Raynaud's syndrome in rheumatoid arthritis.
Authors: G J Carroll, K Withers, C E Bayliss
Journal: Annals of the Rheumatic Diseases (1981)

To test the validity of the putative association between Raynaud's syndrome and rheumatoid arthritis (RA) 277 patients with rheumatic disorders were questioned about cold-induced colour reactions in the extremities. The time to recover digital temperature after brief immersion in ice water was used to confirm the presence of Raynaud's syndrome. The prevalence of Raynaud's syndrome in the 148 patients with RA and the 59 patients with osteoarthritis was 2.7% and 5.1% respectively. It is concluded that Raynaud's syndrome is not a frequent accompaniment of RA, and it is suggested that in view of the close association between Raynaud's syndrome and certain other disorders, such as mixed connective tissue disease and scleroderma, when patients present with polysynovitis and Raynaud's syndrome special consideration should be given to these conditions.
An evaluation of renal tubular DNA laddering in response to oxygen deprivation and oxidant injury.
Authors: M Iwata, D Myerson, B Torok-Storb, R A Zager
Journal: Journal of the American Society of Nephrology (1994)

It has recently been suggested that endonuclease activation and/or apoptosis, possibly triggered by oxidant stress, are important pathogenetic mechanisms in oxygen deprivation/reoxygenation-induced proximal tubular cell death. To explore this possibility, DNA "laddering," a characteristic feature of these processes, was sought in: (1) postischemic rat kidneys (25- or 40-min arterial clamping; 0, 1, 4, 8, 24, and 48 h and 6 days reflow); (2) posthypoxic isolate rat proximal tubular segments and (3) cultured human kidney proximal tubular cells (HK-2) subjected either to energy depletion plus Ca2+ overload (antimycin A plus 2-deoxyglucose plus Ca2+ ionophore A23187), or to H2O2-induced cell death. DNA was subsequently extracted, electrophoresed through agarose gels, and visualized with ethidium bromide or Southern blotting. To maximize ladder detection, DNA samples were also end-labeled with 32P dideoxyadenosine triphosphate with terminal deoxynucleotidyl transferase (tdt), followed by electrophoresis. None of the postischemic DNA samples demonstrated any laddering by either ethidium bromide staining or Southern analysis (apoptotic lymphocyte DNA was a positive control). However, trace laddering was apparent by the tat technique, commencing at 1 h of reflow, peaking at 24 h, and resolving slowly thereafter. This finding correlated with the morphologic expression of tubular necrosis, not apoptosis. Hypoxia/reoxygenation caused proximal tubular segment death (44 to 64%), and HK-2 cells were slowly killed by both the H2O2 and the energy depletion/Ca(2+)-loading protocols. However, neither protocol induced ethidium bromide- or tdt-detectable DNA laddering. It was concluded that: (1) minimal DNA laddering develops postischemia, and this change is reliably detected only by the tdt method; (2) it correlates with the morphologic expression of tubular necrosis, not apoptosis; and (3) in vitro oxidative- and energy depletion-mediated proximal tubular cell death can be dissociated from DNA ladder formation.
Quantification of Macrophage Content in Atherosclerotic Plaques by Optical Coherence Tomography
Authors: Guillermo J. Tearney, Hiroshi Yabushita, Stuart L. Houser, H. Thomas Aretz, Ik-Kyung Jang, Kelly H. Schlendorf, Christopher R. Kauffman, Milen Shishkov, Elkan F. Halpern, Brett E. Bouma
Journal: Circulation (2003)

Background— Macrophage degradation of fibrous cap matrix is an important contributor to atherosclerotic plaque instability. An imaging technology capable of identifying macrophages in patients could provide valuable information for assessing plaque vulnerability. Optical coherence tomography (OCT) is a new intravascular imaging modality that allows cross-sectional imaging of tissue with a resolution of ≈10 μm. The aim of this study was to investigate the use of OCT for identifying macrophages in fibrous caps. Methods and Results— OCT images of 26 lipid-rich atherosclerotic arterial segments obtained at autopsy were correlated with histology. Cap macrophage density was quantified morphometrically by immunoperoxidase staining with CD68 and smooth muscle actin and compared with the standard deviation of the OCT signal intensity at corresponding locations. There was a high degree of positive correlation between OCT and histological measurements of fibrous cap macrophage density ( r =0.84, P &lt;0.0001) and a negative correlation between OCT and histological measurements of smooth muscle actin density ( r =−0.56, P &lt;0.005). A range of OCT signal standard deviation thresholds (6.15% to 6.35%) yielded 100% sensitivity and specificity for identifying caps containing &gt;10% CD68 staining. Conclusions— The high contrast and resolution of OCT enables the quantification of macrophages within fibrous caps. The unique capabilities of OCT for fibrous cap characterization suggest that this technology may be well suited for identifying vulnerable plaques in patients.
Pulmonary lymphangioleiomyomatosis in Korea
Authors: Y.-M. Oh, E. K. Mo, S. H. Jang, C. G. Yoo, Y. W. Kim, J.-W. Seo, S. K. Han, J.-G. Im, Y.-S. Shim
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease occurring in women of reproductive age and leading to progressive respiratory failure in spite of treatment. In Korea the first case was reported in 1984 and by 1997 a total of 23 cases had been reported. The clinical findings of these Korean cases are reviewed. <h3>METHODS</h3> The details of 10 cases of LAM on file at Seoul National University Hospital were reviewed together with those of 13 cases previously reported from other Korean institutes. Two, including the only one to be reported in a man, were excluded after reviewing the clinical, radiological, and pathological findings, leaving a total of 21 cases in the present study. <h3>RESULTS</h3> All 21 patients were women and in all cases the disease was proven pathologically. The mean (SD) age at onset of symptoms was 32 (8.6) years. The most common symptoms were dyspnoea and pneumothorax which were seen in 19 (90%) and 13 (76%) patients, respectively. Pulmonary function tests showed decreased transfer factor (Tlco) (100%) and airflow limitation (67%). All the cases had characteristic cysts on high resolution computed tomographic (HRCT) scanning. The overall severity score based on HRCT scans correlated with the percentage predicted Tlco/Va (p = 0.03) and FEV<sub>1</sub>/FVC (p = 0.02). The patients were all treated with medroxyprogesterone and/or tamoxifen. Follow up was possible in 10 cases. Two of these patients appeared to stabilise with no appreciable change clinically or in lung function on medroxyprogesterone and/or tamoxifen, but the remaining patients all deteriorated with two dying of respiratory insufficiency and one of infection following lung transplantation. <h3>CONCLUSIONS</h3> As in other countries, in Korea LAM occurs exclusively in women and progresses despite hormonal treatment.
Sixteenth Biannual Report of the Cochrane Haematological Malignancies Group: Focus on Non-Hodgkin's Lymphoma
Authors: Olaf Weingart, Fareed A Rehan, Holger Schulz, Frauke Naumann, Ina Knauel, Corinne Brillant Julia Bohlius, Andreas Engert
Journal: JNCI Journal of the National Cancer Institute (2014)

This sixteenth biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials (RCTs) in the field of hemato-oncology, with special focus on non-Hodgkin’s lymphoma. The report covers the publication period June 2012 to July 2013. Trials are selected regarding their methodology and implication for clinical practice. Studies were identified by electronic search of MEDLINE using a broad search filter that covers all topics in hemato-oncology combined with a highly sensitive search filter for randomized trials (Cochrane Handbook for Systematic Reviews of Interventions). Four RCTs are presented in detail, followed by two further RCTs of high importance in a short version. The report is finalized with an overview of new and updated Cochrane Reviews.