tbuckley/cabot-search huggingface dataset:
Clinical Decisions Associated With Positron Emission Tomography in a Prospective Cohort of Patients With Suspected or Known Cancer at One United States Center
Authors: Bruce E. Hillner, Renuka Tunuguntla, Melvin Fratkin
Journal: Journal of Clinical Oncology (2004)

Purpose In 2001, Medicare approved reimbursement of F-18 fluorodeoxyglucose positron emission tomography (PET) for a variety of cancers. PET has been observed to be more accurate than other imaging in cancer patients, but the impact of PET on management in routine practice is uncertain. Patients and Methods We studied a prospective cohort having noninvestigational PET at one university center. Before and after PET, a questionnaire was administered to solicit information regarding each physician's preceding actions, intended management, and probability estimates. Results Seventy-one physicians provided data on 248 patients, of whom 40% had new or suspected cancer and 60% were undergoing restaging or had suspected recurrence. Lung, lymphoma, and head/neck cancers accounted for two thirds of cases. Sixteen physicians made 64% of requests. Physicians changed their intended management in 61% of patients (95% CI, 54% to 66%). For individual physicians ordering at least 10 scans, the average kappa was 0.16 (range, −0.04 to 0.36), reflecting only slight level of agreement between their before and after PET plan. PET was associated with a change in 90 (79%) of 114 patients if the pre-PET intended plan involved more testing or biopsy. In 32% of cases, physicians changed to a treatment from a nontreatment strategy. The therapeutic goal and mode changed in 22 (7%) and 21 cases (8%), respectively. Conclusion This study confirms that physicians often change their decision making based on PET. This impact is likely due to combined effects of PET's improved accuracy and reduced physician uncertainty. Physicians may also be overconfident in interpreting PET and use it as the final arbiter after an extensive evaluation in lieu of tissue biopsy.
Thiazolidinedione-Induced Fluid Retention Is Independent of Collecting Duct αENaC Activity
Authors: Volker Vallon, Edith Hummler, Timo Rieg, Oleh Pochynyuk, Vladislav Bugaj, Jana Schroth, Georges Dechenes, Bernard Rossier, Robyn Cunard, James Stockand
Journal: Journal of the American Society of Nephrology (2009)

Thiazolidinediones are agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) that can induce fluid retention and weight gain through unclear mechanisms. To test a proposed role for the epithelial sodium channel ENaC in thiazolidinedione-induced fluid retention, we used mice with conditionally inactivated alphaENaC in the collecting duct (Scnn1a(loxloxCre) mice). In control mice, rosiglitazone did not alter plasma aldosterone levels or protein expression of ENaC subunits in the kidney, but did increase body weight, plasma volume, and the fluid content of abdominal fat pads, and decreased hematocrit. Scnn1a(loxloxCre) mice provided functional evidence for blunted Na+ uptake in the collecting duct, but still exhibited rosiglitazone-induced fluid retention. Moreover, treatment with rosiglitazone or pioglitazone did not significantly alter the open probability or number of ENaC channels per patch in isolated, split-open cortical collecting ducts of wild-type mice. Finally, patch-clamp studies in primary mouse inner medullary collecting duct cells did not detect ENaC activity but did detect a nonselective cation channel upregulated by pioglitazone. These data argue against a primary and critical role of ENaC in thiazolidinedione-induced fluid retention.
Stem cell-related cardiac gene expression early after murine myocardial infarction
Authors: Susanne Vandervelde, Marja J.A. van Luyn, Mark H. Rozenbaum, Arjen H. Petersen, Rene A. Tio, Martin C. Harmsen
Journal: Cardiovascular Research (2006)

Clinical experimental stem cell therapy after myocardial infarction appears feasible, but its use has preceded the understanding of the working mechanism. The ischemic recipient cardiac environment is determinative for the attraction and subsequent fate of stem cells. Here, we studied expression levels of genes that are anticipated to be essential for adequate stem cell-based cardiac repair at various time-points during the 1 month period following myocardial infarction (MI).Gene expression in the hearts of mice that underwent MI by permanent or transient (30 min) ligation of the coronary artery was monitored using quantitative RT-PCR analysis of mRNA isolated from whole heart sections as well as from specific, laser micro-dissected, regions of sections. Protein expression was performed by immunohistochemical stainings and Western blot analysis.Many inflammatory genes were highly expressed for at least 1 week after MI. The expression of pro-angiogenic genes such as bFGF, VEGF-A and VEGF-R2 changed only marginally post-MI. Markers used to test stem cell gene expression remained unchanged post-MI with the exception of G-CSF and GM-CSF, which are genes that are also known to enhance the inflammatory response. Analysis of micro-dissected regions revealed that SDF-1, SCF (both stem cell attractants) and VEGF-R2 (involved in angiogenesis) gene expression was slightly decreased especially in the infarcted region.Genes that are generally considered to participate in stem cell-related processes and angiogenesis were not upregulated after MI, whereas the inflammatory gene expression dominated. Modulation of this imbalance might be of value for stem cell-mediated therapy.
Abagovomab As Maintenance Therapy in Patients With Epithelial Ovarian Cancer: A Phase III Trial of the AGO OVAR, COGI, GINECO, and GEICO—The MIMOSA Study
Authors: Paul Sabbatini, Philipp Harter, Giovanni Scambia, Jalid Sehouli, Werner Meier, Pauline Wimberger, Klaus H. Baumann, Christian Kurzeder, Barbara Schmalfeldt, David Cibula, Mariusz Bidzinski, Antonio Casado, Andrea Martoni, Nicoletta Colombo, Robert W. Holloway, Luigi Selvaggi, Andrew Li, Jose del Campo, Karel Cwiertka, Tamas Pinter, Jan B. Vermorken, Eric Pujade-Lauraine, Simona Scartoni, Monica Bertolotti, Cecilia Simonelli, Angela Capriati, Carlo Alberto Maggi, Jonathan S. Berek, Jacobus Pfisterer
Journal: Journal of Clinical Oncology (2013)

To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients with ovarian cancer in first clinical remission.Patients with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer in complete clinical remission after primary surgery and platinum- and taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a phase III, double-blind, placebo-controlled, multicenter study. Abagovomab 2 mg or placebo was administered as 1-mL suspension once every 2 weeks for 6 weeks (induction phase) and then once every 4 weeks (maintenance phase) until recurrence or up to 21 months after random assignment of the last patient. The primary end point was RFS; secondary end points were OS and immunologic response.Characteristics of the 888 patients included: mean age, 56.3 years; Eastern Cooperative Oncology Group performance status, ≤ 1 in > 99% of patients; serous papillary subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35 U/mL after third cycle, 80.9%. Mean exposure to study treatment (± standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS for the treatment group using tumor size categorization (≤ 1 cm, > 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P = .322). The most frequently reported type of adverse event was an injection site reaction in 445 patients (50.2%), followed by injection site erythema and fatigue in 227 (25.6%) and 212 patients (23.9%), respectively. By the final visit, median anti-anti-idiotypic antibody level was 493,000.0 ng/mL, indicating a robust response.Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS.
Studies of Atrial Flutter Following Open Heart Surgery
Authors: A L Waldo, J L Wells, V J Plumb, T B Cooper, W A H MacLean
Journal: Annual Review of Medicine (1979)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Pathogenesis of Shigella diarrhea. IX. Simplified high yield purification of Shigella toxin and characterization of subunit composition and function by the use of subunit-specific monoclonal and polyclonal antibodies.
Authors: A Donohue-Rolfe, G T Keusch, C Edson, D Thorley-Lawson, M Jacewicz
Journal: The Journal of Experimental Medicine (1984)

A simple purification scheme for shigella cytotoxin was devised, resulting in high yields (approximately 50%) and a 1,300-fold increase in specific activity compared with the initial crude bacterial cell lysate. The purified toxin was enterotoxic in ligated rabbit ileal loops and neurotoxic when injected into the peritoneal cavity of mice. Measurement of specific activity of cytotoxin and enterotoxin demonstrated that these two toxicities copurify during the fractionation procedure. On sodium dodecyl sulfate gel electrophoresis, the toxin migrated as two polypeptide subunits, an A subunit of 32,000 mol wt and a B subunit of 6,500 mol wt. Chemical cross-linking experiments demonstrate that the toxin is a complex consisting of one A and five B subunits with a molecular weight of 64,000. Polyclonal rabbit anti-toxin and anti-subunit B antisera were produced as well as subunit-specific mouse monoclonal antibodies. All antibodies preincubated with toxin neutralized cytotoxic effects in HeLa cell monolayers. In contrast, only A subunit-specific antibodies were able to neutralize toxin prebound to the HeLa cell surface. Antibody to the B subunit also inhibited binding of 125I-labeled toxin to these cells by 94% or more. These data demonstrate that the B subunit is involved in shigella toxin binding to the cell surface.
Epigenetics of renal cell carcinoma: the path towards new diagnostics and therapeutics
Authors: Mark R Morris, Eamonn R Maher
Journal: Genome Medicine (2010)

Aberrant DNA methylation, in particular promoter hypermethylation and transcriptional silencing of tumor suppressor genes, has an important role in the development of many human cancers, including renal cell carcinoma (RCC). Indeed, apart from mutations in the well studied von Hippel-Lindau gene (VHL), the mutation frequency rates of known tumor suppressor genes in RCC are generally low, but the number of genes found to show frequent inactivation by promoter methylation in RCC continues to grow. Here, we review the genes identified as epigenetically silenced in RCC and their relationship to pathways of tumor development. Increased understanding of RCC epigenetics provides new insights into the molecular pathogenesis of RCC and opportunities for developing novel strategies for the diagnosis, prognosis and management of RCC.
Screening Women for Intimate Partner Violence: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation
Authors: Heidi D. Nelson, Christina Bougatsos, Ian Blazina
Journal: Annals of Internal Medicine (2012)

Background: In 2004, the U.S. Preventive Services Task Force determined that evidence was insufficient to support screening women for intimate partner violence (IPV). Purpose: To review new evidence on the effectiveness of screening and interventions for women in health care settings in reducing IPV and related health outcomes, the diagnostic accuracy of screening instruments, and adverse effects of screening and interventions. Data Sources: MEDLINE and PsycINFO (January 2002 to January 2012), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through fourth quarter 2011), Scopus, and reference lists. Study Selection: English-language trials of the effectiveness of screening and interventions, diagnostic accuracy studies of screening instruments, and studies of any design about adverse effects. Data Extraction: Investigators extracted data about study populations, designs, and outcomes and rated study quality by using established criteria. Data Synthesis: A large fair-quality trial of screening versus usual care indicated reduced IPV and improved health outcomes for both groups, but no statistically significant differences between groups. Fifteen fair- and good-quality studies evaluated 13 screening instruments, and six instruments were highly accurate. Four fair- and good-quality trials of counseling reported reduced IPV and improved birth outcomes for pregnant women, reduced IPV for new mothers, and reduced pregnancy coercion and unsafe relationships for women in family-planning clinics. Fourteen studies indicated minimal adverse effects with screening, but some women experienced discomfort, loss of privacy, emotional distress, and concerns about further abuse. Limitation: Trials were limited by heterogeneity, lack of true control groups, high loss to follow-up, self-reported measures, and lack of accepted reference standards. Conclusion: Screening instruments accurately identify women experiencing IPV. Screening women for IPV can provide benefits that vary by population, while potential adverse effects have minimal effect on most women. Primary Funding Source: Agency for Healthcare Research and Quality.
Insulin Receptor Substrate-1 Is an Important Mediator of Ovarian Cancer Cell Growth Suppression by All-<i>trans</i> Retinoic Acid
Authors: Sharada Ravikumar, Georgina Perez-Liz, Luis Del Vale, Dianne Robert Soprano, Kenneth J. Soprano
Journal: Cancer Research (2007)

Abstract There is a need to identify more effective drugs for the treatment of ovarian cancer as it is the leading cause of death among gynecologic tumors. All-trans retinoic acid (ATRA), a natural retinoid, arrests the growth of CA-OV3 ovarian carcinoma cells in G0-G1. Because the insulin-like growth factor-I receptor has been implicated in the proliferation of various tumors, we investigated its potential role in the suppression of ovarian cancer cell growth by ATRA. Our studies revealed that insulin receptor substrate-1 (IRS-1) protein levels decrease in CA-OV3 cells on ATRA treatment, whereas no differences in IRS-1 levels were seen in the ATRA-resistant SK-OV3 cells. Moreover, CA-OV3 clones overexpressing IRS-1 were growth inhibited less by ATRA, whereas SK-OV3 clones in which levels of IRS-1 were reduced by expression of antisense IRS-1 became sensitive to growth inhibition by ATRA treatment. Studies to determine the mechanism by which ATRA reduced IRS-1 expression showed that ATRA altered steady-state levels of IRS-1 mRNA and the stability of IRS-1 protein. Finally, the role of IRS-1 as a potential molecular target of ATRA in ovarian tumors was assessed by immunohistochemistry in an ovarian cancer tissue array. Compared with normal ovary, the majority of malignant epithelial ovarian tumors overexpressed IRS-1. Thus, there seems to be a correlation between IRS-1 expression and malignancy in ovarian tumors. Our results suggest that IRS-1 is in fact an important growth-regulatory molecule that can be a potential effective target for chemotherapeutic intervention with growth-suppressive agents, including retinoids. [Cancer Res 2007;67(19):9266–75]
VACCINATION WITH HEAT-KILLED AND FORMALINIZED TUBERCLE BACILLI IN EXPERIMENTAL TUBERCULOSIS
Authors: Robert M. Thomas
Journal: The Journal of Experimental Medicine (1933)

1. Rabbits vaccinated with tubercle bacilli killed by exposure to formalin (0.4 per cent) did not show any acquired resistance to subsequent infection with bovine tubercle bacilli, while rabbits vaccinated with tubercle bacilli which had been killed by heating to 70° for 1 hour survived more than half as long again as their controls. 2. Intraperitoneal injection of either the formalin-killed vaccine or the heat-killed vaccine into guinea pigs made them skin-sensitive to tuberculoprotein MA-100. 3. The rate of absorption of the formalin-killed vaccine when introduced beneath the the skin was similar to that of the heat-killed vaccine. 4. Following the intravenous injection of heat-killed tubercle bacilli, it was found that rabbits developed a massive tubercular pneumonia. A study of the production and ultimate absorption of the cellular exudate showed that these processes were similar to those found after the injection of living bacilli. The lesions which followed the injection of heat-killed bacilli differed from the lesions found in active tuberculosis in that in any one animal they showed a striking uniformity in appearance, while in the active disease the lungs showed a great diversity in type of lesion. Studies of the blood cells during the period of injection of dead organisms showed that the changes which are characteristic of the period during which a tuberculous pneumonia develops in rabbits (30 to 40 days after inoculation) were faithfully reproduced. It is suggested that the process of regression described may be similar to that which occurs in childhood tuberculosis, in which rather extensive pulmonary lesions resolve without leaving evidence of damage to the parenchyma of the lung.
REGULATION OF LYMPHOID DEVELOPMENT, DIFFERENTIATION, AND FUNCTION BY THE NOTCH PATHWAY
Authors: Ivan Maillard, Terry Fang, Warren S. Pear
Journal: Annual Review of Immunology (2005)

The Notch pathway is gaining increasing recognition as a key regulator of developmental choices, differentiation, and function throughout the hematolymphoid system. Notch controls the generation of hematopoietic stem cells during embryonic development and may affect their subsequent homeostasis. Commitment to the T cell lineage and subsequent stages of early thymopoiesis is critically regulated by Notch. Recent data indicate that Notch can also direct the differentiation and activity of peripheral T and B cells. Thus, the full spectrum of Notch effects is just beginning to be understood. In this review, we discuss this explosion of knowledge as well as current controversies and challenges in the field.
Long-term Outcome of Women Compared With Men After Successful Coronary Angioplasty
Authors: Malcolm R. Bell, Diane E. Grill, Kirk N. Garratt, Peter B. Berger, Bernard J. Gersh, David R. Holmes
Journal: Circulation (1995)

Background Women who undergo coronary angioplasty have a higher in-hospital mortality than men, although much of this difference can be accounted for by their poorer clinical characteristics at the time of their procedures. However, whether or not there are important long-term differences in outcome between women and men after coronary angioplasty is not clear. Methods and Results A retrospective analysis was performed of 3027 consecutive patients (824 women and 2203 men) who underwent successful angioplasty and who have been followed continuously for a mean of 5.5 years (range, 0.5 to 14 years). Follow-up is 100% complete. Event-free survival was assessed by the Kaplan-Meier method, and clinical end points were also examined by Cox proportional-hazards models to account for important baseline differences when appropriate. There was a trend toward lower survival among women during follow-up, but this was not significant ( P =.06). The relative risk of death among women compared with men after adjustment for baseline differences was 0.94 (CI, 0.76 to 1.15; P =NS). No significant sex differences in occurrence of Q-wave myocardial infarction were observed. Women were less likely to remain free of angina after 10 years (34% versus 37%, respectively; P =.008), but after adjustment for baseline differences, this difference was not significant (relative risk of angina, 1.07; CI, 0.95 to 1.21). Women tended to have less coronary artery bypass surgery performed during follow-up ( P =.06); adjusting for baseline differences made this difference more significant (relative risk, 0.79; CI, 0.64 to 0.96; P =.02). Among patients who were not treated in the setting of acute infarction, no sex differences in survival and freedom from myocardial infarction were noted. Conclusions After successful coronary angioplasty, the long-term prognosis for women is excellent and is similar to that observed in men. Risk-adjusted survival did not differ significantly between the sexes, but less frequent use of subsequent surgical revascularization was observed in women.
Time course and relative dose potency of systemic effects from salmeterol and salbutamol in healthy subjects
Authors: J. A. Bennett, A. E. Tattersfield
Journal: Thorax (1997)

BACKGROUND: The main adverse effects of beta 1 agonists relate to their systemic activity. The time course and dose response relations of the systemic effects of salmeterol compared with salbutamol were investigated. METHODS: A double blind, randomised, crossover study was carried out in 14 healthy subjects who attended on seven days. Heart rate, QTc interval, blood pressure, plasma potassium and glucose concentrations were measured for four hours following inhaled placebo, salmeterol 100, 200 and 400 micrograms and salbutamol 600, 1200 and 2400 micrograms given by metered dose inhaler. Maximum changes from baseline and maximum absolute values following each dose of treatment were used to construct log dose response curves and calculate relative dose potency. RESULTS: Both salmeterol and salbutamol caused dose dependent changes in heart rate, QTc interval, and plasma potassium and glucose concentrations. The onset of cardiac effects was rapid following both drugs, whereas changes in glucose and potassium concentrations occurred more gradually with salmeterol. The increase in heart rate and fall in potassium level were sustained over the four hours whereas glucose levels gradually returned towards baseline. The relative dose potency of salmeterol compared with salbutamol for changes from baseline was 7.1 (95% CI 3.9 to 14.4) for the QTc interval and 8.2 (95% CI 5.7 to 12.6) for plasma potassium concentration. Salmeterol caused steeper dose response curves for heart rate and plasma glucose concentration than salbutamol so relative dose potency values could not be calculated. CONCLUSIONS: These findings support previous data that salmeterol 100 micrograms is broadly equivalent to salbutamol 800 micrograms for systemic effects. The greater systemic effects of salmeterol are most likely to be due to greater potency relative to dose, although it may also have greater systemic bioavailability. The steeper dose response curve for heart rate with salmeterol indicates that it has a narrower therapeutic window than salbutamol and thus should be prescribed at the lowest effective dose.