tbuckley/cabot-search huggingface dataset:
A good death
Authors: J. Grogono
Journal: BMJ (2000)

Editor—May I offer one further ingredient to a good death as discussed by Smith in his editorial1—having an “amicus mortis,” a friend at death. Most items on his list of principles use the word control or imply it, yet the very process of death entails losing control. Control of strong drugs is especially difficult for the one who is dying. An amicus mortis makes it easy. I wrote the following within days of my wife's death from cancer four years ago, and it was read at her funeral.

“Towards the end I was given the privilege of care. I don't want to belittle the role of the care team. None the less, I was the lucky one in charge, especially at night, and my task was an easy one, aided by small doses of morphine towards the end.

“She had no pain, no distress, no loss of dignity, no catheters, none of the things my patients in hospital have to put up with. In the last week our nightly family parties had to be in her room. Her last hours were tranquil.”

The role of amicus mortis is life enhancing, and there should thus be no shortage of supply. I had a further small dose of being an amicus mortis at the end of last year when my father died. My older brother, enviably in full retirement, played the main part. He closed down his home in the Carolinas for a couple of months for the purpose. He endorses this view.

The chosen person must have time and love and prescribing power. Perhaps it is an unfair advantage to have a doctor-husband or doctor-sons available, but prescribing power can easily be delegated, and the other attributes are just as important.

I fully agree with Smith that there is nothing macabre or morbid about thinking of death and planning your funeral throughout life, but I suggest that it is equally important to choose and cultivate your amicus mortis—and see to it that he (or she) doesn't die first.
ALA and photofrin mediated PDT induces apoptosis and necrosis in human breast cancer cells.
Authors: Sarah A. Ziegler, Becky M. Cox, Cherisse R. Loucks, Steen J. Madsen, Stephen W. Carper
Journal: Cancer Research (2006)

5188  Photodynamic therapy (PDT) is a treatment modality that shows promise for the use in a variety of solid tumors and non-cancerous conditions. The present work aims to evaluate the utility of PDT for the treatment of breast cancer. Specifically, we investigated the mechanism by which PDT causes cell cytotoxicity in a number of breast cancer cell lines including - DB46 (engineered to express high constitutive levels of heat shock protein 27 (hsp27)), DC4 (engineered to express normal levels of hsp27) and MDA-MB-435. Investigating hsp27 is important since hsp27 levels are elevated in 40% of breast cancer tumors and this protein has been shown to inhibit apoptosis by binding to cytochrome c. Two FDA-approved photosensitizers (Photofrin and Aminolevulinic acid (ALA)) were evaluated. Clonogenic survival assays demonstrated a light dose dependent response to PDT in all cell lines investigated. The DB46 cell line displayed higher survival at all light doses compared to the DC4 cell line indicating that hsp27 provides protection against PDT-induced cytotoxicity. Flow cytometric analysis showed that PDT induced both apoptosis and necrosis in a light dose dependent manner following ALA-mediated PDT. Preliminary studies with Photofrin mediated-PDT showed greater cell death at all light doses, compared to ALA mediated-PDT. Flow cytometric results also demonstrated hsp27 protection in the DB46 cell lines. These results were confirmed by fluorescent microscopy with both Hoechst and propidium iodide staining. Preliminary data also shows that breast cancer cells undergo necrosis within four hours after PDT treatment. Further investigations into the molecular mechanism of cell death are needed to determine the switch between apoptosis and necrosis after PDT-induced cytotoxicity. Knowledge of PDT-induced mechanisms of cell death will allow for treatment optimization, which is likely to result in an improved prognosis for breast cancer patients.
Complete endoscopic closure of a large gastric defect with endoloop and endoclips after complex endoscopic submucosal dissection
Authors: Seiichiro Abe, Ichiro Oda, Genki Mori, Satoru Nonaka, Haruhisa Suzuki, Shigetaka Yoshianaga, Yutaka Saito
Journal: Endoscopy (2015)

An 83-year-old woman on long-term warfarin and aspirin therapy after aortic valve replacement and coronary stent intervention underwent esophagogastroduodenoscopy for anemia. A protruded lesion was found on the anterior side of the greater curvature of the gastric fundus ([Fig. 1]). This lesion was easily submerged under water in deflation view ([Fig. 2]). The patient opted for endoscopic submucosal dissection (ESD).
Brain Haemodynamics in Intracranial Supratentorial Tumors
Authors: G. Acerbi, G. Liberti, A. Pieri, P. Caciagli
Journal: Neuro-Oncology (1991)

Transcranial Doppler examination of cerebral basal arteries by a 2 MHz probe, provides a simple and noninvasive method for studying cerebral haemodynamics. By this technique tumor vascularization and cerebral vascularization in malignant tumors, mostly cerebral circulation in meningiomas, could be studied (80 supratentorial tumors were examined: 55 gliomas, 10 metastases and 15 meningiomas). Cerebral blood flow velocities are usually reduced in presence of intracranial tumors but sometimes they can be increased due to presence of artero-venous fistulas in glioblastoma or other vascularized tumors, or by direct vascular compression. The haemodynamic effect of mannitol can easily be studied and the rebound effect can be avoided by using small mannitol doses under TCD control in the pre and the post-operative period [1, 2].
Abstract 1896: Chromosome 9p21 Polymorphism Interacts With Waist-to-Hip Ratio in Carotid Plaque
Authors: Ian D Buysschaert, Ernst R Rietzschel, Natacha Lays, Bart Claes, Sofie Bekaert, Peter Verhamme, Guy De Backer, Patrick Segers, Tim De Meyer, Dirk De Bacquer, Thierry Gillebert, Marc De Buyzere, Diether Lambrechts
Journal: Circulation (2009)

Background:  A gene-environment interaction has been suggested between a chromosome 9p21 polymorphism, which confers a major risk for cardiovascular disease, and waist-to-hip ratio (WHR). We further characterized this interaction for carotid atherosclerosis in the larger population-based Asklepios study.   Methods and Results:  We genotyped the rs1333049 polymorphism on chromosome 9p21 in 2,481 healthy individuals aged 35 to 55 years, in which atherosclerotic plaque and intima-media thickness (IMT) were measured in both carotid arteries by a single investigator. We found that the rs1333049 C risk-allele was significantly associated with plaque in carotid arteries in both age- and gender-adjusted and multivariable-adjusted models (Table). No association was seen with IMT. Interestingly, rs1333049 interacted significantly with WHR ( P -values of interaction for plaque in left, right and bilateral carotid arteries, respectively, corrected for age and gender:  P =0.029; 0.051 and 0.004; multivariable adjusted:  P = 0.035; 0.020 and 0.002). Stratification of the cohort according to a WHR equal to or above and below the mean (0.78 for women and 0.92 for men), showed that the risk effect of rs1333049 was confined to abdominal obese individuals only (Table). Stratification by WHO abdominal obesity criteria yielded similar results. No significant interaction was seen for IMT.   Conclusion:  We confirm the interaction between the rs1333049 polymorphism on 9p21 and WHR and demonstrate that the rs1333049 risk-allele increases carotid plaque in abdominal obese individuals only. With the prevalence of obesity increasing rapidly, this interaction is of importance for cardiovascular disease.
Abstract 10843: Low Index of Microcirculatory Resistance Pre PCI Predicts Worsening Microvascular Function post PCI.
Authors: Billal Patel, Paul Browning, George Hart, Michael Fisher
Journal: Circulation (2010)

Background: Microvascular dysfunction following percutaneous coronary intervention (PCI) is known to be significantly associated with adverse outcome. Identification of pre-procedural factors which...
Inhibition of RalB geranylgeranylation is required for GGTI suppression of proliferation and induction of apoptosis
Authors: Samuel C. Falsetti, Adrienne Cox, Channing Der, Said M. Sebti
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3800 

It is estimated that about one hundred human proteins can be geranylgeranylated by the enzyme geranylgeranyltransferase I (GGTase I). Some of these GGTase I substrates are believed to mediate oncogenesis, invasion and metastasis. Furthermore, inhibition of GGTase I with GGTIs result in G1 cell cycle arrest and apoptosis, but the GGTase I substrates critical in GGTI antitumor activity are not known. In this abstract we provide evidence for the involvement of the geranylgeranylated small GTPase RalB. We have made RalA-F and RalB-F mutants that are exclusively farnesylated and showed that, like their wild type geranylgeranylated RalA-GG and RalB-GG, they localize to membranous cellular components. Treatment with FTIs, but not with GGTIs, mislocalized to the cytoplasm RalA-F and RalB-F but not RalA-GG and RalB-GG. Similarly, treatment with GGTIs, but not with FTIs, mislocalized the geranylgeranylated but not the farnesylated forms of the Ral proteins. Importantly, RalB-F but not RalA-F, rescued cells from GGTI induced cell cycle arrest and apoptosis. These data strongly implicate inhibition of RalB geranylgeranylation in the mechanism by which GGTIs inhibit proliferation and induce programmed cell death.
Abstract 2424: Improvement Of Cardiopulmonary Exercise Capacity In Patients With Chronic Post-infarction Heart Failure (CHF) After Intracoronary Infusion Of Bone Marrow-derived Progenitor Cells (BMC)
Authors: Joerg Honold, Lenka Geiger, Ulrich Fischer-Rasokat, Birgit Assmus, Volker Schaechinger, Ioakim Spyridopoulos, Andreas M Zeiher
Journal: Circulation (2008)

Intracoronary (i.c.) infusion of BMC in patients (pts.) with CHF is associated with improvements in left ventricular ejection fraction (LVEF) and reduction of NT-proBNP serum-levels, especially in pts. with more severe heart failure. However, ist is unknown whether the modest improvements in cardiac function translate into an increase in cardiopulmonary exercise capacity. A total of 52 CHF-pts. performed cardiopulmonary exercise tests (CPET) according to a modified Bruce protocol before and 3 months after i.c. infusion of BMC into the infarct-related artery. Anaerobic threshold (AT) was determined by the v-slope method. Overall, pts. were 58±12 years old with a moderately impaired LVEF (mean 42±11%) and a median NYHA-class 2±0.75. NT-proBNP-serum levels were elevated (1007±154 pmol/ml). All pts. received chronic optimized medical therapy with betablockers, ACE-inhibitors and combined diuretics, which was kept constant during the study duration. Initial CPET revealed reduced peak oxygen uptake (peak VO2: 14.0 ml/min/kg), maximal oxygen Pulse (O2Pmax: 11.4 ml/beat) and oxygen uptake at AT (VO2AT: 10.9 ml/min/kg), whereas CO2-equivalents (EqCO2) were elevated (29.7). 3 months after therapy, repeated CPET showed an increase in peak VO2 (14.0±3.9 to 15.3±4.3 ml/min/kg, p=0.07), whereas VO2 AT (10.8±2.5 to 10.8±2.5 ml/min/kg, p= n.s.), O2Pmax (11.2 ± 3.1 to 12.0±3.3 ml/beat, p= n.s.) or EqCO2 (29.7±6.4 to 29.8±6.8, p= n.s.) remained unchanged. However, after dichotomizating the patient cohort according to the median of VO2max at baseline, pts. with lower initial VO2max showed a significant improvement in VO2max (12.8±1.5 to 13.5±2.7ml/min/kg, p= 0.03) and an improvement in VO2AT (9.1±1.8 to 9.5±2.2 ml/min/kg, p= ns), as well as a reduction of EqCO2 (34.7±7.1 to 33.8±8.0, p= ns). In contrast, pts. with initial VO2max &gt; median did not show any significant improvements. These findings indicate that intracoronary BMC-therapy improves exercise capacity in CHF-patients with more advanced heart failure. Therefore, cardiopulmonary exercise testing might help to identify pts. more likely to derive functional benefit from intracoronary BMC administration.
Abstract 18476: NO Resistance in Angiotensin II-Induced Hypertension is Associated With Soluble Guanylyl Cyclase Desensitization via Cysteine Oxidation
Authors: Pierre-Antoine Crassous, Samba Couloubaly, Xavier Fioramonti, David Kim, Padmamalini Baskaran, Walter N Duran, Annie Beuve
Journal: Circulation (2010)

Nitric oxide (NO) stimulates soluble guanylyl cyclase (sGC) to increase cGMP, which causes vasodilation in vascular smooth muscle cells (SMC). We discovered that disease-associated blunted response...
The MAPK inhibitor, MKP3, is an estrogen receptor α coactivator associated with tamoxifen resistance
Authors: Yukun Cui, Mao Zhang, Irma Parra, C. Kent Osborne, Susan G. Hilsenbeck, Anna Tsimelzon, Suzanne A. W. Fuqua
Journal: Cancer Research (2005)

4364  Tamoxifen (Tam) is the most frequently prescribed antiestrogen for the prevention and treatment of ER positive breast cancers, but while Tam is initially useful in many breast cancer patients, tamoxifen resistance (TR) eventually will develop. It has been shown recently that enhanced growth factor signaling is associated with TR, but the mechanisms are still undefined. To examine acquired resistance, we performed a microarray expression profiling study to identify genes associated with clinical TR with two groups of tumors: Tam Sensitive (TS, n=4) were primary tumors from patients who were treated with Tam and had not experienced a recurrence, and TR tumors (n=5) were metastatic breast tumors from patients who were treated with Tam and whose metastatic lesions recurred while on treatment. We found that the major cellular inhibitor of MAPK, MAPK Phosphatase 3 (MKP3, also called DUSP6), was significantly overexpressed in the TR group of tumors. Since we observed that there were two “LXXLL” motifs, called NR boxes, in MKP3 with similarity to nuclear receptor interaction domains, we hypothesized that MKP3 could interact with ER, and function as an ERα coactivator protein. Through transient transactivation assay, we demonstrated that MKP3 could potentiate ligand-induced ERα activity in ERα-positive breast cancer cell lines in a dose-dependent manner. We also found that MKP3 expression enhances ligand-dependent transcriptional activity of other nuclear receptors, such as androgen receptor, progesterone receptor, and retinoic acid receptor, but not a TATA-box driven promoter, demonstrating specificity for nuclear receptors. We next engineered MCF-7 cells to stably overexpress MKP3 to study its effects on estrogen-induced growth and tamoxifen response. MKP3 overexpression led to significantly increased growth in soft agar in the presence of tamoxifen which could be inhibited by the pure steroidal antiestrogen fulvestrant. A preliminary experiment demonstrated that MKP3 overexpression did not affect estrogen-stimulated xenograft growth compared with vector-control tumors. However, in the Tam-treated groups, the MKP3 expressing xenografted tumors continued to grow (p=0.047), suggesting that MKP3 overexpression might confer TR in ERα-positive breast cancer cells. In estrogen-treated MKP3 transfectants, MAPK was inhibited. But we observed increased phospho-ERK1/2 levels, and phosphorylation at S118 ERα in tamoxifen-treated MKP3-overexpressing cells, suggesting that the interaction of ERα and MKP3 might represent a novel mechanism independent of its effects on MAPK. Alternatively, MKP3 overexpression overexpression may lead to a paradoxical activation of MAPK in tamoxifen-treated tumors. In summary, our data suggest that MKP3 is a new ERα coactivator which may be involved in the evolution of clinical resistance.
Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia
Authors: Enrico Tiacci, Jae H. Park, Luca De Carolis, Stephen S. Chung, Alessandro Broccoli, Sasinya Scott, Francesco Zaja, Sean Devlin, Alessandro Pulsoni, Young R. Chung, Michele Cimminiello, Eunhee Kim, Davide Rossi, Richard M. Stone, Giovanna Motta, Alan Saven, Marzia Varettoni, Jessica K. Altman, Antonella Anastasia, Michael R. Grever, Achille Ambrosetti, Kanti R. Rai, Vincenzo Fraticelli, Mario E. Lacouture, Angelo M. Carella, Ross L. Levine, Pietro Leoni, Alessandro Rambaldi, Franca Falzetti, Stefano Ascani, Monia Capponi, Maria P. Martelli, Christopher Y. Park, Stefano A. Pileri, Neal Rosen, Robin Foà, Michael F. Berger, Pier L. Zinzani, Omar Abdel-Wahab, Brunangelo Falini, Martin S. Tallman
Journal: New England Journal of Medicine (2015)

BRAF V600E is the genetic lesion underlying hairy-cell leukemia. We assessed the safety and activity of the oral BRAF inhibitor vemurafenib in patients with hairy-cell leukemia that had relapsed after treatment with a purine analogue or who had disease that was refractory to purine analogues.
Expression of LHRH receptors in prostate cancer cells prior to therapy, following castration, or following treatment with LHRH agonists
Authors: S. Liu, A. V. Schally, S. Xiong, R. Cote, D. Hawes, L. Fazli, M. Gleave, J. Cai, F. Brands, J. Engel, J. Pinski
Journal: Journal of Clinical Oncology (2009)

5163 Background: In the treatment of advanced prostate cancer, the effects of luteinizing hormone releasing hormone (LHRH) agonists are mediated through the down-regulation of pituitary LHRH receptors, inhibiting the pituitary-gonadal axis. Several groups have demonstrated LHRH receptor expression on prostate cancer cells. These tumoral receptors have been shown to mediate direct inhibitory effects in vitro. That expression of LHRH receptors persists in the castrate resistant state. To date, there is no information on LHRH receptor expression on the prostate after LHRH agonist therapy. This study investigates the expression of LHRH receptors following prolonged exposure to LHRH agonists. Methods: Expression of LHRH receptors was determined using immunohistochemistry and the intensity was graded on a scale from zero to 3. The expression was analyzed in three cohorts of patients: (1) 47 men with localized prostate cancer treated with radical prostatectomy with no hormone therapy, (2) 61 men with localized prostate cancer treated with neoadjuvant LHRH agonists for varying duration prior to prostatectomy, and (3) 22 men with metastatic prostate cancer who received a palliative transurethral resection of the prostate after clinical progression. In the final cohort, 15 men were treated with castration and 7 were treated with LHRH agonists. Results: 45 of 47 hormone naïve samples (95.7%) demonstrated LHRH receptor expression. Statistical analysis revealed a correlation between strong receptor expression and higher pathologic tumor stage as well as shorter overall survival. 60 of 61 samples treated with neoadjuvant LHRH agonist therapy (98.4%) demonstrated LHRH receptor expression. All 22 samples from patients with metastatic disease demonstrated LHRH receptor expression. The majority of these samples demonstrated moderate to strong intensity. Conclusions: LHRH receptors are expressed on prostate cancers cells of hormone naïve and castrated patients. The expression of these receptors appears to persist despite prolonged treatment with LHRH agonists. The continued expression of these receptors supports the concept of targeting prostatic LHRH receptors to deliver cytotoxic therapy based on LHRH analogs, such as AN-152. [Table: see text]
Risk Stratification Model for Resected Squamous-Cell Lung Cancer Patients According to Clinical and Pathological Factors
Authors: Sara Pilotto, Isabella Sperduti, Silvia Novello, Umberto Peretti, Michele Milella, Francesco Facciolo, Sabrina Vari, Giovanni Leuzzi, Tiziana Vavalà, Antonio Marchetti, Felice Mucilli, Lucio Crinò, Francesco Puma, Stefania Kinspergher, Antonio Santo, Luisa Carbognin, Matteo Brunelli, Marco Chilosi, Aldo Scarpa, Giampaolo Tortora, Emiolio Bria
Journal: Journal of Thoracic Oncology (2015)
Intravenous Anti-D Treatment of Immune Thrombocytopenic Purpura: Experience in 272 Patients
Authors: Andromachi Scaradavou, Bonnie Woo, B.M.R. Woloski, Susanna Cunningham-Rundles, Lawrence J. Ettinger, Louis M. Aledort, James B. Bussel
Journal: Blood (1997)
Functional Expression of Fas (CD95) in Acute Myeloid Leukemia Cells in the Context of CD34 and CD38 Expression: Possible Correlation With Sensitivity to Chemotherapy
Authors: Narikazu Iijima, Koichi Miyamura, Toshihide Itou, Mitsune Tanimoto, Ryou Sobue, Hidehiko Saito
Journal: Blood (1997)
The Use Of GDP (Gemcitabine, Dexamethasone and Cisplatin) in The Primary Therapy Of Peripheral T-Cell Lymphomas
Authors: Jean-Michel Lavoie, Joseph M. Connors, Diego Villa, Richard Klasa, Tamara Shenkier, Randy D. Gascoyne, Alina S. Gerrie, Laurie H. Sehn, Kerry J. Savage
Journal: Blood (2013)
Abstract 17545: Effect of Long-Term Circulatory Support on Arterial Wall: Comparison of Histological Findings in Pulsatile and Continuous Flow Blood Pump Recipients
Authors: Evgenij V Potapov, Alexander Stepanenko, Sajjad Rezaei, Lars Morawietz, Hans B Lehmkuhl, Yuguo Weng, Miralem Pasic, Thomas Krabatsch, Roland Hetzer
Journal: Circulation (2011)

Background. Continuous flow (CF) ventricular assist devices (VAD) are an established option for treatment of end-stage heart failure. However, the impact of long-term continuous flow with lack of peripheral arterial wall motions on blood pressure regulation and end-organ arterial wall sclerosis, especially in the case of long-term support (over 3 years), remains unclear. Methods: Samples of arterial wall (liver, kidney, coronary and cerebral arteries) from a total of 33 autopsies of VAD recipients treated between September 2000 and July 2009 were examined for perivascular infiltrate index, intravascular infiltrate index, wall thickness, thrombosis, entdothelial cell swelling, vessel wall necrosis and perivascular fibrosis. In ten patients (group P) pulsatile devices, and in 23 patients CF devices had been inserted (group CF). The pathologist was blinded to the group distribution. Additionally, clinical course and follow-up data were retrospectively analyzed. Results: Median duration of support in group P was 432 days (range 177-1588 days) and in group CF 351 days (range 182-942 days). There were no differences in doses of ACE-inhibitors, beta-blockers, aldactone and diuretics. During follow-up amiodaron was more often used in the CF group than the P group (61% vs. 10%, p=0.009). Throughout the follow-up period mean arterial pressure did not differ between recipients of the two pump types. Diastolic blood pressure in CF device recipients was lower after 3 months of support only (figure). Histological studies did not recognize any relevant differences in arterial wall characteristics between the two groups. Conclusion: Chronic mechanical circulatory support for up to 4 years with CF devices does not adversely influence arterial wall properties of the end-organ vasculature.
Rheumatoid Meningitis Presenting With Multiple Strokelike Episodes
Authors: Bhaskar Roy, Dean F. Uphoff, Isaac E. Silverman
Journal: JAMA Neurology (2015)

cortex (14.2% astrocytes; 4.8% neurons; 325 cells), 6.4% in CA1 (18% astrocytes; 9.6% neurons; 941 cells), 5.7% in caudatum (20% astrocytes; 6.4% neurons; 470 cells), and 5.3% in cerebellum (3.2% astrocytes; 6.0% neurons; 225 cells).Discussion | Greco et al 6 described the presence of inclusions in 11 cases of men with FXTAS aged 67 to 87 years.In our patient, the number of inclusions were in the low range when compared with those cases.In summary, FXTAS is thought to be a disorder of aging in carriers of FMR1 premutation; however, this case documents that FXTAS can occur earlier in adult life, particularly if another disease process is occurring, such as substance abuse, that may exacerbate the pathological process of FXTAS.