tbuckley/cabot-search huggingface dataset:
Routine Chest Roentgenography Is Unnecessary in the Work-Up of Stage I and II Breast Cancer
Authors: E. Alexandra Chen, Gregory A. Carlson, Bret F. Coughlin, William P. Reed, Jane L. Garb, James L. Frank
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Clinical practice guidelines of many professional societies call for routine staging chest x-rays (SCXR) for all patients with invasive cancer. Given the estimated 157,000 patients annually for whom this recommendation pertains, this screening examination represents a considerable health care expenditure. If it were shown that SCXR rarely changed the management of low-risk subsets of this population, it might be possible to selectively omit this practice from the care of these patients with substantial resultant cost savings. PATIENTS AND METHODS: All patients with clinical stage I and II breast cancer presenting to the Baystate Medical Center from 1989 through 1997 were identified through the Tumor Registry. Their hospital records were reviewed for clinical presentation and documentation of SCXR. RESULTS: One thousand four hundred ninety-four patients were identified with clinical stage I and II disease. SCXR were available for review on 1,003 patients. Only one asymptomatic patient was upstaged to stage IV based on a SCXR. Two patients with primary lung tumors were also identified. These data demonstrate an asymptomatic pulmonary metastasis detection rate of 0.099% (95% confidence interval, 0.0% to 0.6%). The total charges of SCXR for this group approached $180,000. CONCLUSION: These data demonstrate the low diagnostic yield and high cost of routine SCXR in the management of asymptomatic patients with clinical stage I and stage II breast cancer. Because other studies have shown that SCXR changes neither quality of life nor overall survival, SCXR should be limited to symptomatic patients in whom metastatic disease is suspected.
Targeting xCT, a cystine-glutamate transporter induces apoptosis and tumor regression for KSHV/HIV-associated lymphoma
Authors: Lu Dai, Yueyu Cao, Yihan Chen, Chris Parsons, Zhiqiang Qin
Journal: Journal of Hematology & Oncology (2014)

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of primary effusion lymphoma (PEL), which represents a rapidly progressing malignancy arising in HIV-infected patients. Conventional chemotherapy for PEL treatment induces unwanted toxicity and is ineffective — PEL continues to portend nearly 100% mortality within a period of months, which requires novel therapeutic strategies. The amino acid transporter, xCT, is essential for the uptake of cystine required for intracellular glutathione (GSH) synthesis and for maintaining the intracellular redox balance. Inhibition of xCT induces growth arrest in a variety of cancer cells, although its role in virus-associated malignancies including PEL remains unclear. In the current study, we identify that xCT is expressed on the surface of patient-derived KSHV+ PEL cells, and targeting xCT induces caspase-dependent cell apoptosis. Further experiments demonstrate the underlying mechanisms including host and viral factors: reducing intracellular GSH while increasing reactive oxygen species (ROS), repressing cell-proliferation-related signaling, and inducing viral lytic genes. Using an immune-deficient xenograft model, we demonstrate that an xCT selective inhibitor, Sulfasalazine (SASP), prevents PEL tumor progression in vivo. Together, our data provide innovative and mechanistic insights into the role of xCT in PEL pathogenesis, and the framework for xCT-focused therapies for AIDS-related lymphoma in future.
Programming of Implantable Cardioverter-Defibrillators on the Basis of the Upper Limit of Vulnerability
Authors: Charles D. Swerdlow, C. Thomas Peter, Robert M. Kass, Eli S. Gang, William J. Mandel, Chun Hwang, David J. Martin, Peng-Sheng Chen
Journal: Circulation (1997)

Background A patient-specific measure of defibrillation efficacy that requires a minimum number of ventricular fibrillation (VF) episodes would be valuable for programming implantable cardioverter-defibrillators (ICDs). The upper limit of vulnerability (ULV) is the weakest shock strength at or above which VF is not induced when a stimulus is delivered during the vulnerable phase of the cardiac cycle. It correlates with the defibrillation threshold (DFT) and can be determined with a single episode of VF. The objective of this study was to test the hypothesis that ICDs programmed on the basis of the ULV convert spontaneous ICD-detected VF reliably. Methods and Results We studied 100 consecutive patients at ICD implantation and during follow-up of 20±7 months. At implantation, the ULV and DFT were determined, and the ICD system was tested at a shock strength equal to the ULV+3 J. During follow-up, the strength of the first shock was programmed to the ULV+5 J for arrhythmias detected in the VF zone (cycle length &lt;292±17 ms). We reviewed stored detection intervals and electrograms from spontaneous episodes of ICD-detected VF to determine the success rate for appropriate first shocks. The programmed first-shock strength was 17.5±5.2 J. During follow-up, there were 120 appropriate first shocks in 37 patients. The arrhythmia was rapid monomorphic ventricular tachycardia (VT) in 70% of episodes (31 patients), VF in 11% (13 patients), polymorphic VT in 1%, and unclassified in 17% (15 patients). The first shock was successful in 119 of 120 episodes (99%; 95% CI, 93% to 100%). One unclassified episode required two shocks. No patient had syncope associated with an ICD shock or arrhythmic death. Conclusions ICD shocks can be programmed on the basis of the ULV, a measurement made in regular rhythm, without a direct measure of defibrillation efficacy.
Phosphoproteomic Analysis Reveals Regulatory Mechanisms at the Kidney Filtration Barrier
Authors: Markus M. Rinschen, Xiongwu Wu, Tim König, Trairak Pisitkun, Henning Hagmann, Caroline Pahmeyer, Tobias Lamkemeyer, Priyanka Kohli, Nicole Schnell, Bernhard Schermer, Stuart Dryer, Bernard R. Brooks, Pedro Beltrao, Marcus Krueger, Paul T. Brinkkoetter, Thomas Benzing
Journal: Journal of the American Society of Nephrology (2014)

Diseases of the kidney filtration barrier are a leading cause of ESRD. Most disorders affect the podocytes, polarized cells with a limited capacity for self-renewal that require tightly controlled signaling to maintain their integrity, viability, and function. Here, we provide an atlas of in vivo phosphorylated, glomerulus-expressed proteins, including podocyte-specific gene products, identified in an unbiased tandem mass spectrometry-based approach. We discovered 2449 phosphorylated proteins corresponding to 4079 identified high-confidence phosphorylated residues and performed a systematic bioinformatics analysis of this dataset. We discovered 146 phosphorylation sites on proteins abundantly expressed in podocytes. The prohibitin homology domain of the slit diaphragm protein podocin contained one such site, threonine 234 (T234), located within a phosphorylation motif that is mutated in human genetic forms of proteinuria. The T234 site resides at the interface of podocin dimers. Free energy calculation through molecular dynamic simulations revealed a role for T234 in regulating podocin dimerization. We show that phosphorylation critically regulates formation of high molecular weight complexes and that this may represent a general principle for the assembly of proteins containing prohibitin homology domains.
Towards Theranostic Multicompartment Microcapsules: in-situ Diagnostics and Laser-induced Treatment
Authors: Ranhua Xiong, Stefaan J. Soenen, Kevin Braeckmans, Andre G. Skirtach
Journal: Theranostics (2013)

Paving the way towards the application of polyelectrolyte multilayer capsules in theranostics, we describe diagnostic multi-functionality and drug delivery using multicompartment polymeric capsules which represent the next generation of drug delivery carriers. Their versatility is particularly important for potential applications in the area of theranostics wherein the carriers are endowed with the functionality for both diagnostics and therapy. Responsiveness towards external stimuli is attractive for providing controlled and on-demand release of encapsulated materials. An overview of external stimuli is presented with an emphasis on light as a physical stimulus which has been widely used for activation of microcapsules and release of their contents. In this article we also describe existing and new approaches to build multicompartment microcapsules as well as means available to achieve controlled and triggered release from their subcompartments, with a focus on applications in theranostics. Outlook for future directions in the area are highlighted.
Absorption of inhaled antigen into the circulation of isolated lungs from normal and immunized rabbits.
Authors: J F Braley, C A Dawson, V L Moore, B O Cozzini
Journal: Journal of Clinical Investigation (1978)

The purpose of this study was to determine whether the absorption of inhaled antigen (Ag) across the pulmonary air-blood barrier of the isolated perfused lung can be modulated by immunologic mechanisms. Lungs from immunized or nonimmunized rabbits were removed, ventilated, and perfused with autochthonous blood. Radioiodinated Ag (human serum albumin or ovalbumin) was introduced as an aerosol into the isolated lung for 15 min and blood samples were taken over a 4-h period. The results showed that radioactivity fom inhaled Ag entered the perfusing blood as two fractions. One fraction was precipitable by 5% trichloroacetic acid or antiserum. The TCA-soluble fraction chromatographed differently from iodide and may have represented metabolites of the Ag. Immunization specifically reduced the amount of antigenically intact protein entering the blood. On the other hand, the metabolite reached higher concentrations in the blood of immunized lungs. We conclude that the alveolar capillary barrier of the normal rabbit lung could provide a significant route of entry for inhaled antigen into the systemic circulation and that immunization reduces absorption via this route and enhances pulmonary metabolism of the Ag.
Physiotherapy for anterior knee pain: a randomised controlled trial
Authors: D I Clark, N Downing, J Mitchell, L Coulson, E P Syzpryt, M Doherty
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To determine the efficacy of the individual components of physiotherapy in subjects with anterior knee pain. <h3>METHODS</h3> An observer blind, prospective, factorial design randomised controlled trial. 81 young adults with anterior knee pain were randomly allocated to one of four treatment groups: (1) exercise, taping, and education; (2) exercise and education; (3) taping and education; and (4) education alone. Each group received six physiotherapist-led treatments over three months. Follow up took place at three months using the following outcome measures: patient satisfaction (discharge/refer for further treatment); a visual analogue pain score; the WOMAC lower limb function score; the Hospital Anxiety and Depression scale (HAD); and quadriceps strength. At 12 months the WOMAC and HAD were assessed by postal questionnaire. <h3>RESULTS</h3> All groups showed significant improvements in WOMAC, visual analogue, and HAD scores; these improvements did not vary significantly between the four groups or between exercising/non-exercising and taped/non-taped patients at three and 12 months. However, patients who exercised were significantly more likely to be discharged at three months than non-exercising patients (χ<sup>2</sup>, p&lt;0.001). Taping was not significantly associated with discharge. Significantly greater improvements in WOMAC, visual analogue, and the anxiety score (but not the depression score) were seen in patients who were discharged than in those who were referred. <h3>CONCLUSIONS</h3> The proprioceptive muscle stretching and strengthening aspects of physiotherapy have a beneficial effect at three months sufficient to permit discharge from physiotherapy. These benefits are maintained at one year. Taping does not influence the outcome.
Private aspects of heterologous immunity
Authors: Barbara Rehermann, Eui-Cheol Shin
Journal: The Journal of Experimental Medicine (2005)

Clinical manifestations of viral infections are highly variable, both in type and severity, among individual patients. Differences in host genetics and in dose and route of infection contribute to this variability but do not fully explain it. New studies now show that each subject's history of past infections individualizes the memory T cell pool. Private T cell receptor specificities of these preexisting memory T cell populations influence both disease severity and outcome of subsequent, unrelated virus infections.
The Functional Assessment of Cancer Therapy scale: development and validation of the general measure.
Authors: D F Cella, D S Tulsky, G Gray, B Sarafian, E Linn, A Bonomi, M Silberman, S B Yellen, P Winicour, J Brannon
Journal: Journal of Clinical Oncology (1993)

PURPOSE We developed and validated a brief, yet sensitive, 33-item general cancer quality-of-life (QL) measure for evaluating patients receiving cancer treatment, called the Functional Assessment of Cancer Therapy (FACT) scale. METHODS AND RESULTS The five-phase validation process involved 854 patients with cancer and 15 oncology specialists. The initial pool of 370 overlapping items for breast, lung, and colorectal cancer was generated by open-ended interview with patients experienced with the symptoms of cancer and oncology professionals. Using preselected criteria, items were reduced to a 38-item general version. Factor and scaling analyses of these 38 items on 545 patients with mixed cancer diagnoses resulted in the 28-item FACT-general (FACT-G, version 2). In addition to a total score, this version produces subscale scores for physical, functional, social, and emotional well-being, as well as satisfaction with the treatment relationship. Coefficients of reliability and validity were uniformly high. The scale's ability to discriminate patients on the basis of stage of disease, performance status rating (PSR), and hospitalization status supports its sensitivity. It has also demonstrated sensitivity to change over time. Finally, the validity of measuring separate areas, or dimensions, of QL was supported by the differential responsiveness of subscales when applied to groups known to differ along the dimensions of physical, functional, social, and emotional well-being. CONCLUSION The FACT-G meets or exceeds all requirements for use in oncology clinical trials, including ease of administration, brevity, reliability, validity, and responsiveness to clinical change. Selecting it for a clinical trial adds the capability to assess the relative weight of various aspects of QL from the patient's perspective.
Herders of Indian and European Cattle Share Their Predominant Allele for Lactase Persistence
Authors: Irene Gallego Romero, Chandana Basu Mallick, Anke Liebert, Federica Crivellaro, Gyaneshwer Chaubey, Yuval Itan, Mait Metspalu, Muthukrishnan Eaaswarkhanth, Ramasamy Pitchappan, Richard Villems, David Reich, Lalji Singh, Kumarasamy Thangaraj, Mark G. Thomas, Dallas M. Swallow, Marta Mirazón Lahr, Toomas Kivisild
Journal: Molecular Biology and Evolution (2011)

Milk consumption and lactose digestion after weaning are exclusively human traits made possible by the continued production of the enzyme lactase in adulthood. Multiple independent mutations in a 100-bp region—part of an enhancer—approximately 14-kb upstream of the LCT gene are associated with this trait in Europeans and pastoralists from Saudi Arabia and Africa. However, a single mutation of purported western Eurasian origin accounts for much of observed lactase persistence outside Africa. Given the high levels of present-day milk consumption in India, together with archaeological and genetic evidence for the independent domestication of cattle in the Indus valley roughly 7,000 years ago, we sought to determine whether lactase persistence has evolved independently in the subcontinent. Here, we present the results of the first comprehensive survey of the LCT enhancer region in south Asia. Having genotyped 2,284 DNA samples from across the Indian subcontinent, we find that the previously described west Eurasian -13910 C>T mutation accounts for nearly all the genetic variation we observed in the 400- to 700-bp LCT regulatory region that we sequenced. Geography is a significant predictor of -13910*T allele frequency, and consistent with other genomic loci, its distribution in India follows a general northwest to southeast declining pattern, although frequencies among certain neighboring populations vary substantially. We confirm that the mutation is identical by descent to the European allele and is associated with the same >1 Mb extended haplotype in both populations.
Detection of Renal Function Decline in Patients with Diabetes and Normal or Elevated GFR by Serial Measurements of Serum Cystatin C Concentration
Authors: Bruce A. Perkins, Robert G. Nelson, Betsy E.P. Ostrander, Kristina L. Blouch, Andrzej S. Krolewski, Bryan D. Myers, James H. Warram
Journal: Journal of the American Society of Nephrology (2005)

Research on early renal function decline in diabetes is hampered by lack of simple tools for detecting trends (particularly systematic decreases) in renal function over time when GFR is normal or elevated. This study sought to assess how well serum cystatin C meets that need. Thirty participants with type 2 diabetes in the Diabetic Renal Disease Study met these three eligibility criteria: GFR >20 ml/min per 1.73 m2 at baseline (based on cold iothalamate clearance), 4 yr of follow-up, and yearly measurements of iothalamate clearance and serum cystatin C. With the use of linear regression, each individual's trend in renal function over time, expressed as annual percentage change in iothalamate clearance, was determined. Serum cystatin C in mg/L was transformed to its reciprocal (100/cystatin C), and linear regression was used to determine each individual's trend over time, expressed as annual percentage change. In paired comparisons of 100/cystatin C with iothalamate clearance at each examination, the two measures were numerically similar. More important, the trends in 100/cystatin C and iothalamate clearance were strongly correlated (Spearman r = 0.77). All 20 participants with negative trends in iothalamate clearance (declining renal function) also had negative trends for 100/cystatin C. Results were discordant for only three participants. In contrast, the trends for three commonly used creatinine-based estimates of GFR compared poorly with trends in iothalamate clearance (Spearman r < 0.35). Serial measures of serum cystatin C accurately detect trends in renal function in patients with normal or elevated GFR and provide means for studying early renal function decline in diabetes.
Immunotherapy with partially purified and standardized tree pollen extracts
Authors: B. Nüchel Petersen, H. Janniche, E. P. Munch, J.Å. Wihl, H. Böuwadt, H. Ipsen, H. Löswenstein
Journal: Allergy (1988)

Fifty‐four adult patients with tree pollen‐induced rhinitis (28), asthma (1), or rhinitis and asthma (25) were selected for immunotherapy with standardized and partly purified tree pollen extracts using a double blind protocol. The selection was based on clinical history, results of nasal or bronchial challenge, skin prick tests and RAST. Further, based on crossed radio‐immunoelectrophoresis, sex, age and severity of symptoms, the patients were allocated in matched pairs and the treatment alternatives were randomly distributed within the pairs. Twenty‐three patients treated with extracts composed of any combination of alder, birch and hazel pollen which matched their IgE response in CRIE (Group 1 (ABC)) and 22 patients receiving birch pollen extracts (Group 2 (B)) completed ail 3 years of treatment. The in vivo results comprising symptom and medicine consumption scores are given here. Changes in specific skin and nasal reactivity as well as in immunological parameters arc presented separately. No significant differences were demonstrated between the treatment groups in the two parameters. Both extracts were effective and reduced in general the symptom scores to one tenth of the starting level. Expressed another way, at the end of the study, the patients tolerated 30 times more pollen until symptoms of the same severity were elicited, compared to before. In the Nordic countries, spring‐time asthma and rhino‐conjunctivitis caused by pollen from deciduous trees can be effectively treated with an extract of birch pollen alone.
Spleen stiffness: Toward a noninvasive portal sphygmomanometer?
Authors: Juan G. Abraldes, Enric Reverter, Annalisa Berzigotti, Roberto J. Groszmann, Yasuko Iwakiri, Tamar H. Taddei
Journal: Hepatology (2013)

BACKGROUND AND AIMS: The hepatic vein pressure gradient (HVPG) is the standard used to determine the degree of portal hypertension (PH) and an important prognostic factor for patients with cirrhosis; HVPG values correlate with the presence of esophageal varices (EV). However, HVPG can only be accurately determined at specialized centers; noninvasive methods are needed to predict HVPG values and the presence of EV. We compared the diagnostic performance of spleen stiffness (SS) measurement by transient elastography with that of liver stiffness (LS) and of other recently proposed noninvasive tests. METHODS: We measured SS and LS in 100 consecutive patients with hepatitis C virus-induced cirrhosis. Patients were also assessed by FibroScan, HVPG, esophagogastroduodenoscopy, and liver biopsy. We also analyzed LS-spleen diameter to platelet ratio score and platelet count to spleen diameter. RESULTS: SS and LS were more accurate than other noninvasive parameters in identifying patients with EV and different degrees of PH. A linear model that included SS and LS accurately predicted HVPG values (R(2) = 0.85). The results were internally validated using bootstrap analysis. CONCLUSIONS: Measurement of SS can be used for noninvasive assessment and monitoring of PH and to detect EV in patients with hepatitis C virus-induced cirrhosis.
Bleomycin Pulmonary Toxicity Has a Negative Impact on the Outcome of Patients With Hodgkin's Lymphoma
Authors: William G. Martin, Kay M. Ristow, Thomas M. Habermann, Joseph P. Colgan, Thomas E. Witzig, Stephen M. Ansell
Journal: Journal of Clinical Oncology (2005)

Bleomycin pulmonary toxicity (BPT) has been well described in Hodgkin's lymphoma (HL) patients treated with bleomycin-containing chemotherapy regimens. The influence of this pulmonary complication, along with the omission of bleomycin from further chemotherapy, on overall survival (OS) and progression-free survival (PFS) in HL remains unclear. We reviewed our experience with BPT in HL to better delineate outcome and appropriate treatment in these patients.One hundred forty-one patients who were treated with bleomycin-containing chemotherapy for newly diagnosed HL between January 1986 and February 2003 were eligible for this retrospective review. BPT was defined by the presence of pulmonary symptoms, bilateral interstitial infiltrates, and no evidence of an infectious etiology.BPT was observed in 18% of patients. Increasing age, doxorubicin, bleomycin, vinblastine, and dacarbazine as initial therapy, and granulocyte colony-stimulating factor use were associated with the development of BPT. Patients with BPT had a median 5-year OS rate of 63% v 90% (P = .001) in unaffected patients. The mortality rate from BPT was 4.2% in all patients and 24% in patients who developed the pulmonary syndrome. BPT incidence and mortality were highest in patients older than 40 years. The omission of bleomycin had no impact on obtaining a complete remission, PFS, or OS.BPT results in a significant decrease in 5-year OS in patients who are treated for HL. Age > or = 40 years seems to add substantially to the risk. In patients who do not die from acute pulmonary toxicity, both OS and PFS seem equal, despite the omission of bleomycin.