tbuckley/cabot-search huggingface dataset:
Long-term Satisfaction and Psychological and Social Function Following Bilateral Prophylactic Mastectomy
Authors: Marlene H. Frost
Journal: JAMA (2000)

ContextProphylactic mastectomy is a preventive option for women who wish to reduce their risk of breast cancer. There has been concern about possible negative psychological sequelae following this procedure. However, few data are available regarding long-term satisfaction and psychological and social function following this procedure.ObjectiveTo evaluate patients' long-term satisfaction and psychological and social function following prophylactic mastectomy.Design, Setting, and ParticipantsDescriptive study of all women known to be alive (n = 609) who had a family history of breast cancer and elected to undergo bilateral prophylactic mastectomy at a large, tertiary US health care clinic between 1960 and 1993, 94% (n = 572) of whom completed a study questionnaire.Main Outcome MeasuresSatisfaction with procedure and effects on psychological and social function, based on responses to the study-specific questionnaire.ResultsMean time from prophylactic mastectomy to last follow-up was 14.5 years. Most women (70%) were satisfied with the procedure; 11% were neutral; and 19% were dissatisfied. Among the psychological and social variables, the most striking finding was that 74% reported a diminished level of emotional concern about developing breast cancer. The majority of women reported no change/favorable effects in levels of emotional stability (68%/23%), level of stress (58%/28%), self-esteem (69%/13%), sexual relationships (73%/4%), and feelings of femininity (67%/8%). Forty-eight percent reported no change in their level of satisfaction with body appearance; 16% reported favorable effects. However, 9%, 14%, 18%, 23%, 25%, and 36% reported negative effects in these 6 variables, respectively.ConclusionsThis study suggests that positive outcomes following prophylactic mastectomy include decreased emotional concern about developing breast cancer and generally favorable psychological and social outcomes. These must be weighed against the irreversibility of the decision, potential problems with implants and reconstructive surgery, and occurrence of adverse psychological and social outcomes in some women.
Lack of effect of dextromethorphan on breathlessness and exercise performance in patients with chronic obstructive pulmonary disease (COPD)
Authors: AE Giron, DW Stansbury, CE Fischer, RW Light
Journal: European Respiratory Journal (1991)

We have previously shown that the exercise performance of patients with severe chronic obstructive pulmonary disease (COPD) can be increased with the administration of oral morphine (0.8 mg.kg-1). The purpose of this study was to determine whether the administration of dextromethorphan (DXT), an antitussive structurally similar to codeine, would result in increased exercise performance and decreased dyspnoea in patients with COPD, without the side-effects of opiates. Six eucapnic patients (mean age = 66 +/- 3.8 yrs) with COPD (mean forced expiratory volume in one second (FEV1) = 1.01 +/- 0.07 l) underwent two incremental cycle ergometer tests to exhaustion (Emax) and assessment of their hypercapnic and hypoxic ventilatory responses and mouth occlusion pressure responses following first the oral administration of placebo (P) and then dextromethorphan (60 mg) in a single-blind fashion. There was no statistically significant difference in the maximal exercise performance, perceived dyspnoea (modified Borg scale), breathing pattern or expired gases after the two different treatments. In addition, the ventilatory response to CO2 production during exercise (delta VE/VCO2) and the ventilatory and mouth occlusion pressure responses to hypoxia and hypercapnia did not differ significantly after DXT as compared with after P. Indeed the exercise performance was poorer and the ventilatory responses were brisker after DXT. We conclude from this study that the administration of this opiate analogue does not improve the exercise capacity or decrease the ventilatory response of patients with COPD.
Lung cancer risk in a population-based cohort of patients hospitalized for asthma in Sweden
Authors: P. Boffetta, W. Ye, G. Boman, O. Nyrén
Journal: European Respiratory Journal (2002)

It has been suggested that asthma increases the risk of lung cancer in males but not in females. However, previous studies may suffer from report bias and are based on a small numbers of cases. The objective of the present study was to assess the incidence of lung cancer in males and females using a nationwide Swedish cohort of asthma patients. Patients (n=92,986) aged ≥20 yrs with a hospital-discharge diagnosis of asthma and who were alive and free from malignancy 1 yr after first hospitalization were followed-up, for incidence of lung cancer during the period 1965–1994 (average duration of follow-up, 8.5 yrs). Their incidence of lung cancer was compared with that of the national population. The authors observed 713 lung cancers (standardized incidence ratio (SIR) 1.58, 95% confidence interval (CI) 1.47–1.70). The SIR was 1.51 in males (95% CI 1.38–1.65, 492 cases) and 1.78 in females (95% CI 1.55–2.03, 221 cases). The SIR decreased with duration of follow-up and increased with calendar period and age at first hospitalization. The risk of lung cancer was higher for squamous cell and small cell carcinoma than for adenocarcinoma, and it was higher in patients with other diseases as the main diagnosis and in patients hospitalized in departments other than internal and respiratory medicine. It was confirmed that asthma patients are at increased risk of lung cancer, but there is no heterogeneity in risk between the sexes. Several indirect arguments point towards a noncausal explanation of these findings; in particular, confounding by tobacco smoking is a plausible explanation.
Monocyte migration to the synovium in rheumatoid arthritis patients treated with adalimumab
Authors: M M J Herenius, R M Thurlings, C A Wijbrandts, R J Bennink, S E Dohmen, C Voermans, D Wouters, E S Izmailova, D M Gerlag, B L F van Eck-Smit, P P Tak
Journal: Annals of the Rheumatic Diseases (2011)

Objectives The mechanism of action of treatment with tumour necrosis factor (TNF) blockers in rheumatoid arthritis (RA) is still not completely understood. The aim of this study was to test if adalimumab treatment could affect the influx of monocytes into the synovium. Methods A novel technique was used to analyse the migration of labelled autologous monocytes before and 14 days after initiation of adalimumab treatment using scintigraphy. CD14 monocytes were isolated from patients with RA, using a positive selection procedure with magnetic-activated cell sorting, and labelled with technetium-99m-hexamethylpropylene-amino-oxime. Scintigraphic scans were made 1, 2 and 3 h after re-infusion. Results As early as 14 days after the start of treatment with adalimumab a significant decrease in disease activity score evaluated in 28 joints was shown. There was no significant decrease in the influx of monocytes into the joint at this time. Conclusions This study indicates that adalimumab treatment does not reduce the influx of monocytes into the synovium early after initiation of treatment. As previous studies showed a rapid decrease in macrophage infiltration after TNF-antibody therapy, which could not be explained by increased cell death, this points to an important role for enhanced efflux of inflammatory cells from the synovium.
Rapid Turnover of Connexin43 in the Adult Rat Heart
Authors: Michael A. Beardslee, James G. Laing, Eric C. Beyer, Jeffrey E. Saffitz
Journal: Circulation Research (1998)

Abstract —Remodeling of the distribution of gap junctions is an important feature of anatomic substrates of arrhythmias in patients with healed myocardial infarcts. Mechanisms underlying this process are poorly understood but probably involve changes in gap junction protein (connexin) synthesis, assembly into channels, and degradation. The half-life of the principal cardiac gap junction protein, connexin43 (Cx43), is only 1.5 to 2 hours in primary cultures of neonatal myocytes, but it is unknown whether rapid turnover of Cx43 occurs in the adult heart or is unique to disaggregated neonatal myocytes that are actively reestablishing connections in vitro. To characterize connexin turnover dynamics in the adult heart and to elucidate its potential role in remodeling of gap junctions, we measured Cx43 turnover kinetics and characterized the proteolytic pathways involved in Cx43 degradation in isolated perfused adult rat hearts. Hearts were labeled for 40 minutes with Krebs-Henseleit buffer containing [ 35 S]methionine, and then chase perfusions were performed with nonradioactive buffer for 0, 60, 120, and 240 minutes. Quantitative immunoprecipitation assays of Cx43 radioactivity in 4 hearts at each time point yielded a monoexponential decay curve indicating a Cx43 half-life of 1.3 hours. Proteolytic pathways responsible for Cx43 degradation were elucidated by perfusing isolated rat hearts for 4 hours with specific inhibitors of either lysosomal or proteasomal proteolysis. Immunoblot analysis demonstrated significant increases (≈30%) in Cx43 content in hearts perfused with either lysosomal or proteasomal pathway inhibitors. Most of the Cx43 in hearts perfused with lysosomal inhibitors consisted of phosphorylated isoforms, whereas nonphosphorylated Cx43 accumulated selectively in hearts perfused with a specific proteasomal inhibitor. These results indicate that Cx43 turns over rapidly in the adult heart and is degraded by multiple proteolytic pathways. Regulation of Cx43 degradation could play an important role in gap junction remodeling in response to cardiac injury.
Association Between Vancomycin Minimum Inhibitory Concentration and Mortality Among Patients With<i>Staphylococcus aureus</i>Bloodstream Infections
Authors: Andre C. Kalil, Trevor C. Van Schooneveld, Paul D. Fey, Mark E. Rupp
Journal: JAMA (2014)

<h3>Importance</h3> <i>Staphylococcus aureus</i>bacteremia (SAB) is a worldwide problem. It is unclear whether higher-vancomycin minimum inhibitory concentration (MIC) is associated with mortality. This potential association has direct consequences for patients and public health. <h3>Data Sources</h3> PubMed, Embase, the Cochrane Library, Evidence-based Medicine BMJ, and the American College of Physicians Journal Club were searched from inception through April 2014. <h3>Study Selection</h3> Studies reporting mortality and vancomycin MIC in patients with SAB were included. <h3>Data Extraction and Synthesis</h3> Two authors performed the literature search and the study selection separately. Random-effects modeling was used for all analyses. <h3>Main Outcomes and Measures</h3> All-cause mortality. <h3>Findings</h3> Among 38 included studies that involved 8291 episodes of SAB, overall mortality was 26.1%. The estimated mortality was 26.8% among SAB episodes (n = 2740) in patients with high-vancomycin MIC (≥1.5 mg/L) compared with 25.8% mortality among SAB episodes (n = 5551) in patients with low-vancomycin MIC (&lt;1.5 mg/L) (adjusted risk difference [RD], 1.6% [95% CI, −2.3% to 5.6%];<i>P</i> = .43). For the highest-quality studies, the estimated mortality was 26.2% among SAB episodes (n = 2318) in patients with high-vancomycin MIC compared with 27.8% mortality among SAB episodes (n = 4168) in patients with low-vancomycin MIC (RD, 0.9% [95% CI, −2.9% to 4.6%];<i>P</i> = .65). In studies that included only methicillin-resistant<i>S aureus</i>infections (n = 7232), the mortality among SAB episodes (n = 2384) in patients with high-vancomycin MIC was 27.6% compared with mortality of 27.4% among SAB episodes (n = 4848) in patients with low-vancomycin MIC (adjusted RD, 1.6% [95% CI, −2.3% to 5.5%];<i>P</i> = .41). No significant differences in risk of death were observed in subgroups with high-vancomycin MIC vs low-vancomycin MIC values across different study designs, microbiological susceptibility assays, MIC cutoffs, clinical outcomes, duration of bacteremia, previous vancomycin exposure, and treatment with vancomycin. <h3>Conclusions and Relevance</h3> In this meta-analysis of SAB episodes, there were no statistically significant differences in the risk of death when comparing patients with<i>S aureus</i>exhibiting high-vancomycin MIC (≥1.5 mg/L) to those with low-vancomycin MIC (&lt;1.5 mg/L), although the findings cannot definitely exclude an increased mortality risk. These findings should be considered when interpreting vancomycin susceptibility and in determining whether alternative antistaphylococcal agents are necessary for patients with SAB with elevated but susceptible vancomycin MIC values.
Macrophage Markers in Serum and Tumor Have Prognostic Impact in American Joint Committee on Cancer Stage I/II Melanoma
Authors: Trine O. Jensen, Henrik Schmidt, Holger Jon Møller, Morten Høyer, Maciej Bogdan Maniecki, Pia Sjoegren, Ib Jarle Christensen, Torben Steiniche
Journal: Journal of Clinical Oncology (2009)

Purpose To evaluate the prognostic role of soluble CD163 (sCD163) in serum and macrophage infiltration in primary melanomas from patients with American Joint Committee on Cancer (AJCC) stage I/II melanoma. The scavenger receptor CD163 is associated with anti-inflammatory macrophages, and it is shed from their surface. Patients and Methods Serum samples from 227 patients with stage I/II melanoma obtained before definitive surgery (baseline) and during 5 years of follow-up were analyzed for sCD163 by enzyme-linked immunosorbent assay. Excised formalin-fixed, paraffin-embedded primary melanomas from 190 patients were available for immunohistochemical analyzes of CD163 + and CD68 + macrophage infiltration. They were estimated semiquantitatively in three different tumor compartments: tumor nests, tumor stroma, and at the invasive front of the tumor. Results Serum sCD163 treated as an updated continuous covariate as well as the baseline value were analyzed together with the covariate's ulceration and thickness in a Cox proportional hazards model. sCD163 was an independent prognostic factor for overall survival (baseline, hazard ratio [HR] = 1.4; 95% CI, 1.1 to 1.7; P = .01; and updated, HR = 1.4; 95% CI, 1.1 to 1.8; P = .003). Melanomas with dense CD163 + macrophage infiltration in tumor stroma and CD68 + macrophage infiltration at the invasive front were associated with poor overall survival (CD163, HR = 2.7; 95% CI, 0.8 to 9.3; P = .11; and CD68, HR = 2.8; 95% CI, 1.2 to 6.8; P = .02) independent (borderline for CD163) of thickness and ulceration. Conclusion Both serum levels of sCD163 and the presence of CD68 + macrophage infiltration at the tumor invasive front are independent predictors of survival in AJCC stage I/II melanoma. CD163 + cell infiltration in tumor stroma may be predictive of survival.
Scintigraphy in a Patient with Complicated Osteopetrosis
Authors: B K ADAMS
Journal: Clinical Nuclear Medicine (1989)

Skeletal, reticuloendothelial and renal images were obtained on a patient with osteopetrosis using Tc-99m MDP, Tc-99m HSA millimicrospheres and Tc-99m DTPA respectively. The bone scan showed increased uptake in multiple fracture sites, in the frontal bone, and in the splayed metaphyses of long bones while the remainder of the skeleton appeared normal. Reticuloendothelial images demonstrated an absence of bone marrow activity, hepatosplenomegaly and a site of extramedullary hematopoiesis. A renogram demonstrated a left kidney displaced and distorted by the massive splenomegaly.
Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial
Authors: Susan R Kahn, Stan Shapiro, Philip S Wells, Marc A Rodger, Michael J Kovacs, David R Anderson, Vicky Tagalakis, Adrielle H Houweling, Thierry Ducruet, Christina Holcroft, Mira Johri, Susan Solymoss, Marie-José Miron, Erik Yeo, Reginald Smith, Sam Schulman, Jeannine Kassis, Clive Kearon, Isabelle Chagnon, Turnly Wong, Christine Demers, Rajendar Hanmiah, Scott Kaatz, Rita Selby, Suman Rathbun, Sylvie Desmarais, Lucie Opatrny, Thomas L Ortel, Jeffrey S Ginsberg
Journal: The Lancet (2013)
Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B
Authors: Seokjoon Lee, Qian Wang
Journal: Medicinal Research Reviews (2006)

Abstract Protein tyrosine phosphatases (PTPs), a large family of signaling enzymes, play essential roles in intracellular signal transduction by regulating the cellular level of tyrosine phosphorylation to control cell growth and differentiation, metabolism, cell migration, gene transcription, ion‐channel activity, immune response, cell apoptosis, and bone development. Among all PTPs, protein tyrosine phosphatase 1B (PTP1B) plays a seminal role in cellular signaling and in many human diseases, including cancer, diabetes, and obesity. Therefore, small molecular inhibitors of PTP1B can be promising drug candidates. Because of the structural homologies in many families of PTPs, it is a challenging task to find inhibitors specific to each PTP. Recent studies suggested that secondary binding pockets or peripheral binding sites around the conserved active site should be exploited to design novel potent and selective PTP1B inhibitors. In this review, we discuss the structural and biological features of small molecular PTP1B‐specific inhibitors, with particular emphasis on small molecular inhibitors targeting PTP1B over the other PTPs that have been synthesized in the past 4 years. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 4, 553–573, 2007
Consensus: a framework for evaluation of uncertain gene variants in laboratory test reporting
Authors: David K Crockett, Perry G Ridge, Andrew R Wilson, Elaine Lyon, Marc S Williams, Scott P Narus, Julio C Facelli, Joyce A Mitchell
Journal: Genome Medicine (2012)

Accurate interpretation of gene testing is a key component in customizing patient therapy. Where confirming evidence for a gene variant is lacking, computational prediction may be employed. A standardized framework, however, does not yet exist for quantitative evaluation of disease association for uncertain or novel gene variants in an objective manner. Here, complementary predictors for missense gene variants were incorporated into a weighted Consensus framework that includes calculated reference intervals from known disease outcomes. Data visualization for clinical reporting is also discussed.
Anti-Cytokine Therapy for Rheumatoid Arthritis
Authors: R. N. Maini, P. C. Taylor
Journal: Annual Review of Medicine (2000)

▪ Abstract Tumor necrosis factor α (TNFα) and interleukin-1 (IL-1) are important in mediating inflammation in rheumatoid arthritis (RA). Randomized phase II and III clinical trials of anti-TNF reagents (infliximab and etanercept) have demonstrated an acceptable safety profile and marked clinical efficacy in cases of RA that have not responded adequately to conventional therapy. Combination therapy with methotrexate (MTX) appears to be particularly effective in patients whose disease activity persists despite prior disease-modifying antirheumatic drugs (DMARDs) and ongoing MTX monotherapy. DMARD-recalcitrant disease may become the main indication for the use of anti-TNF drugs in patients with RA. Trials of IL-1 receptor antagonist show a relatively modest anti-inflammatory effect and a possible retardation of joint damage. Whether anti-TNF therapy protects joints from structural damage is under investigation. One anti-TNF reagent has already been approved in the United States for the treatment of RA, and other cytokine antagonists or agonists are under development.
A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: results of Cancer and Leukemia Group B (CALGB) 90102
Authors: G.K. Philips, S. Halabi, B.L. Sanford, D. Bajorin, E.J. Small
Journal: Annals of Oncology (2009)
Human lung volumes and the mechanisms that set them
Authors: DE Leith, R Brown
Journal: European Respiratory Journal (1999)

Definitions of human lung volumes and the mechanisms that set them are reviewed in the context of pulmonary function testing, with attention to the distinction between functional residual capacity (FRC) and the static relaxation volume of the respiratory system, and to the circumstances in which FRC and residual volume are set by dynamic rather than by static mechanisms. Related terms, conventions, and issues are addressed, including some common semantic and conceptual difficulties, with attention to "gas trapping", "hyperinflation", and "restriction".
Oral antiviral therapy for hepatitis B: the case of besifovir, a new kid on the block with a long way to go
Authors: Pietro Lampertico
Journal: Gut (2013)

In the last 5 years, the landscape of HBV antiviral treatment has changed significantly to such an extent that most of the clinical problems have been solved for countries where third-generation nucleo s(t)ide analogues (NUC), such as entecavir (ETV) and tenofovir (TDF) are routinely available.1–⇓3 Indeed, because of the high potency and high genetic barrier of these products, 5–6 years administration of ETV or TDF suppresses viral replication in >95% of the cases, with increasing rates of HBeAg seroconversion (up to 50%) and HBsAg seroconversion (up to 10%). In patients with long-lasting viral suppression, histological fibrosis is reverted, cirrhosis can regress and clinical decompensation is fully prevented, whereas, hepatocellular carcinoma (HCC) remains the only complication leading to anticipated liver-related death and liver transplantation.4–⇓⇓⇓8 In patients with decompensated cirrhosis, administration of ETV and TDF improves survival, though the early mortality rates and the development HCC despite effective viral suppression do represent major challenges for these delicate patients. Likewise, the management of NUC-resistant (NUC-R) patients has also been revolutionised by the availability of TDF which efficiently suppresses as monotherapy viral replication in most patients, independently of the resistant profile.9 Though efficacy must remain the major endpoint of any anti-HBV therapy, safety has also attracted much of attention in recent years, given that antiviral treatment must be prolonged for several years, even decades, for most patients, as HBsAg clearance remains the best stopping rule even in cirrhotics. Even in this regard, ETV and TDF have shown a good safety profile over extended periods (up to …