tbuckley/cabot-search huggingface dataset:
Recent developments in pain in dementia
Authors: Erik Scherder, Joukje Oosterman, Dick Swaab, Keela Herr, Marcel Ooms, Miel Ribbe, Joseph Sergeant, Gisele Pickering, Fabrizio Benedetti
Journal: BMJ (2005)

Epidemiological studies show that, worldwide, the number of people aged over 65 will increase substantially in the next decades and that a considerable proportion of this population will develop dementia.1 Ample evidence shows that ageing is associated with a high rate of painful conditions, irrespective of cognitive status.2 The number of patients with dementia who will experience painful conditions is therefore likely to increase. A key question relates to whether and how patients with dementia perceive pain. Patients with dementia may express their pain in ways that are quite different from those of elderly people without dementia.3 Particularly in the more severe stages of dementia, therefore, the complexity and consequent (frequent) inadequacy of pain assessment leads to the undertreatment of pain.

The most commonly used pain assessment instruments seem to be selected primarily according to the communicative capacity of the patient (self report pain rating scales for communicative patients and observation scales for non-communicative patients) instead of according to two main aspects of pain—the sensory-discriminative and motivational-affective aspects. In particular, the motivational-affective aspects of pain are assessed by observation scales, which should therefore be applied to every patient, irrespective of ability to communicate. Distinction between the sensory-discriminative and motivational-affective aspects of pain is of great clinical relevance, as the motivational-affective aspects are particularly likely to reflect pain that needs treatment.4 Moreover, differentiating between these two aspects of pain in relation to the neuropathology of the various subtypes of dementia provides insight into the basis of the alterations in the pain experiences of elderly people with dementia. Future experimental and clinical studies should not only focus on subtypes of dementia but should go a step further and assess pain in disorders in which pain is already present at a stage without cognitive impairment and during the course …
Mice deficient in IL-1beta manifest impaired contact hypersensitivity to trinitrochlorobenzone.
Authors: L P Shornick, P De Togni, S Mariathasan, J Goellner, J Strauss-Schoenberger, R W Karr, T A Ferguson, D D Chaplin
Journal: The Journal of Experimental Medicine (1996)

Mice rendered deficient in IL-1 beta by gene targeting in embryonic stem cells develop and grow normally in a protected laboratory environment. Endotoxin-stimulated peritoneal macrophages from IL-1beta-deficient mice showed normal synthesis and cellular release of IL-1alpha after treatment with 5 mM ATP demonstrating that IL-1beta is not necessary for expression and release of the IL-1alpha isoform. Mice deficient in IL-1beta showed unaltered sensitivity to endotoxic shock, with or without pretreatment with D-galactosamine. In contrast, IL-1beta-deficient mice showed defective contact hypersensitivity responses to topically applied trinitrochlorobenzene (TNCB). This defect could be overcome either by application of very high doses of sensitizing antigen, or by local intradermal injection of recombinant IL-1beta immediately before antigen application. These data demonstrate an essential role for IL-1beta in contact hypersensitivity and suggest that IL-1beta acts early during the sensitization phase of response. They suggest an important role for IL-1beta in initiation of the host of response at the epidermal barrier.
Decreased Endogenous Production of Hydrogen Sulfide Accelerates Atherosclerosis
Authors: Sarathi Mani, Hongzhu Li, Ashley Untereiner, Lingyun Wu, Guangdong Yang, Richard C. Austin, Jeffrey G. Dickhout, Šárka Lhoták, Qing H. Meng, Rui Wang
Journal: Circulation (2013)

Cystathionine γ-lyase (CSE) produces hydrogen sulfide (H2S) in the cardiovascular system. The deficiency of CSE in mice leads to a decreased endogenous H2S level, an age-dependent increase in blood pressure, and impaired endothelium-dependent vasorelaxation. To date, there is no direct evidence for a causative role of altered metabolism of endogenous H2S in atherosclerosis development.Six-week-old CSE gene knockout and wild-type mice were fed with either a control chow or atherogenic paigen-type diet for 12 weeks. Plasma lipid profile and homocysteine levels, blood pressure, oxidative stress, atherosclerotic lesion size in the aortic roots, cell proliferation, and adhesion molecule expression were then analyzed. CSE-knockout mice fed with atherogenic diet developed early fatty streak lesions in the aortic root, elevated plasma levels of cholesterol and low-density lipoprotein cholesterol, hyperhomocysteinemia, increased lesional oxidative stress and adhesion molecule expression, and enhanced aortic intimal proliferation. Treatment of CSE-knockout mice with NaHS, but not N-acetylcysteine or ezetimibe, inhibited the accelerated atherosclerosis development. Double knockout of CSE and apolipoprotein E gene expression in mice exacerbated atherosclerosis development more than that in the mice with only apolipoprotein E or CSE knockout.Endogenously synthesized H2S protects vascular tissues from atherogenic damage by reducing vessel intimal proliferation and inhibiting adhesion molecule expression. Decreased endogenous H2S production predisposes the animals to vascular remodeling and early development of atherosclerosis. The CSE/H2S pathway is an important therapeutic target for protection against atherosclerosis.
Response to ifosfamide and mesna: 124 previously treated patients with metastatic or unresectable sarcoma.
Authors: K H Antman, L Ryan, A Elias, D Sherman, H E Grier
Journal: Journal of Clinical Oncology (1989)

European and American investigators have reported response rates of 38% to 83% for ifosfamide alone in pretreated sarcomas. In a phase II trial of ifosfamide 2.0g/m2 days 1 to 4 with mesna uroprotection in 124 patients with previously failed sarcomas, four (3%) responded completely (95% exact confidence interval, 1% to 8%) and 26 (21%) had a complete or partial response (95% exact confidence interval, 14% to 29%). The median time to progression was 5 and 9 months for partial and complete responders, respectively. In the subset of soft tissue sarcomas, the response rate for the patients receiving bolus administration was 26%, compared with 9% for the patients receiving a continuous infusion schedule (P = .03). The response rates among patients with soft tissue and bony sarcomas with a performance score of 0-2 and 0-1 prior to chemotherapy administration were 20% and 40%, respectively. Somnolence or confusion developed in 19%. Neurotoxicity was significantly associated with poor performance status (P less than .01), elevated creatinine (P less than .01), and low bicarbonate levels (P = .05). A serum bicarbonate less than 20 developed in 31% of the patients and was significantly associated with older age (P = .01), elevated creatinine (P = .02), and female sex (P = .06). Hematuria was significantly associated with no uroprotection (the first four patients did not receive mesna because it was unavailable), but was not associated with prior cyclophosphamide, pelvic radiotherapy, age, or bolus v continuation infusion schedule. Thus, ifosfamide is active in failed sarcomas and warrants further study in previously untreated patients with sarcoma.
Stereotactic radiosurgery for recurrent malignant gliomas.
Authors: W A Hall, H R Djalilian, P W Sperduto, K H Cho, B J Gerbi, J P Gibbons, M Rohr, H B Clark
Journal: Journal of Clinical Oncology (1995)

To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas.We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA).The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury.Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.
Adipocyte-Derived Plasma Protein Adiponectin Acts as a Platelet-Derived Growth Factor-BB–Binding Protein and Regulates Growth Factor–Induced Common Postreceptor Signal in Vascular Smooth Muscle Cell
Authors: Yukio Arita, Shinji Kihara, Noriyuki Ouchi, Kazuhisa Maeda, Hiroshi Kuriyama, Yoshihisa Okamoto, Masahiro Kumada, Kikuko Hotta, Makoto Nishida, Masahiko Takahashi, Tadashi Nakamura, Iichiro Shimomura, Masahiro Muraguchi, Yasukazu Ohmoto, Tohru Funahashi, Yuji Matsuzawa
Journal: Circulation (2002)

Background — Vascular smooth muscle cell proliferation plays an important role in the development of atherosclerosis. We previously reported that adiponectin, an adipocyte-specific plasma protein, accumulated in the human injured artery and suppressed endothelial inflammatory response as well as macrophage-to-foam cell transformation. The present study investigated the effects of adiponectin on proliferation and migration of human aortic smooth muscle cells (HASMCs). Methods and Results — HASMC proliferation was estimated by [ 3 H] thymidine uptake and cell number. Cell migration assay was performed using a Boyden chamber. Physiological concentrations of adiponectin significantly suppressed both proliferation and migration of HASMCs stimulated with platelet-derived growth factor (PDGF)-BB. Adiponectin specifically bound to 125 I-PDGF-BB and significantly inhibited the association of 125 I-PDGF-BB with HASMCs, but no effects were observed on the binding of 125 I-PDGF-AA or 125 I-heparin–binding epidermal growth factor (EGF)–like growth factor (HB-EGF) to HASMCs. Adiponectin strongly and dose-dependently suppressed PDGF-BB–induced p42/44 extracellular signal–related kinase (ERK) phosphorylation and PDGF β-receptor autophosphorylation analyzed by immunoblot. Adiponectin also reduced PDGF-AA–stimulated or HB-EGF–stimulated ERK phosphorylation in a dose-dependent manner without affecting autophosphorylation of PDGF α-receptor or EGF receptor. Conclusions — The adipocyte-derived plasma protein adiponectin strongly suppressed HASMC proliferation and migration through direct binding with PDGF-BB and generally inhibited growth factor–stimulated ERK signal in HASMCs, suggesting that adiponectin acts as a modulator for vascular remodeling.
Raised plasma concentrations of platelet factor 4 (PF4) in Crohn's disease.
Authors: M Simi, S Leardi, M T Tebano, M Castelli, F M Costantini, V Speranza
Journal: Gut (1987)

Plasma platelet factor 4 (PF4), secreted by the platelets, is an index of platelet aggregation and thromboembolic risk. The authors assessed PF4 in 20 patients with Crohn9s disease (ileitis in 13 patients, ileocolitis in seven) and in 20 healthy volunteers. Disease activity was low (Crohn9s Disease Activity Index less than 150) in 11 patients and high in nine. Radioimmunoassay of PF4 using Abbott9s Kit was performed on one sample of plasma from each subject (nv less than or equal to 0.324 nmol/ml), (nv less than or equal to 10 ng/ml). A significantly higher concentration of PF4 was found in Crohn9s disease patients: 4.625 +/- 1.1 nmol/ml (142.5 +/- 36 ng/ml) than in the control group: 0.189 +/- 0.07 nmol/ml (5.6 +/- 4.8 ng/ml) (Z = 5.396, p less than 0.0001). No correlation was present between PF4 levels and activity, the site of disease, or medical treatment with or without prednisone.
Dietary Lignan Intake and Postmenopausal Breast Cancer Risk by Estrogen and Progesterone Receptor Status
Authors: M. S. Touillaud, A. C. M. Thiebaut, A. Fournier, M. Niravong, M.-C. Boutron-Ruault, F. Clavel-Chapelon
Journal: JNCI Journal of the National Cancer Institute (2007)

BackgroundStudies conducted in Asian populations have suggested that high consumption of soy-based foods that are rich in isoflavone phytoestrogens is associated with a reduced risk of breast cancer. However, the potential associations of other dietary phytoestrogens—i.e., the lignans or their bioactive metabolites, the enterolignans—with the risk of breast cancer are unclear.
Single live cell TGF-β signalling imaging: breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity
Authors: Rodney B Luwor, Dulani Hakmana, Josephine Iaria, Thao V Nheu, Richard J Simpson, Hong-Jian Zhu
Journal: Molecular Cancer (2015)

Metastasis is a process where only a small subset of cells is capable of successfully migrating to and propagating at secondary sites. TGF-β signalling is widely known for its role in cancer metastasis and is associated with cell migration in whole cell populations. We extend these findings by investigating the role of TGF-β signalling in promoting migration and motility by imaging the signalling activity in live, individual MDA-MB-231 cancer cells utilizing a novel Smad3 Td-Tomato reporter adenovirus. Here we find that not all MDA-MB-231 cancer cells have similar TGF-β mediated Smad3 transcription activity and display at least two distinct migratory populations. Importantly, Smad3 activity was significantly higher within migratory cells compared to non-migrated cells in wound healing and transwell assays. Furthermore, time-lapse experiments showed that MDA-MB-231 cells displaying Smad3 activity moved faster and a greater distance compared to cells not displaying Smad3 reporter activity. Interestingly, despite being more motile than cells with undetectable levels of Smad3 activity, high Smad3 activity was detrimental to cell motility compared to low and medium level of Smad3 activity. We have developed a method enabling real-time visualization of TGF-β signalling in single live cells. Breast cancer cell motility and migration is driven by sub-populations of cells with dynamic TGF-β-Smad3 activity. Those sub-populations may be responsible for tumor invasion and metastasis.
106 ADRENAL DYSFUNCTION IN NONSEPTIC CIRRHOTIC PATIENTS WITH ASCITES: IMPACT ON SURVIVAL
Authors: C. Elia, C. Alessandria, L. Mezzabotta, A. Risso, A. Andrealli, M. Spandre, A. Morgando, A. Marzano, M. Rizzetto
Journal: Journal of Hepatology (2011)
Cardiopulmonary bypass tubes and prime solutions stimulate neutrophil adhesion molecules
Authors: M El Habbal
Journal: Cardiovascular Research (1997)

To evaluate effects of the material of the cardiopulmonary bypass (CPB) tubes (polyvinyl chloride, PVC) and prime solutions on expression of neutrophil adhesion molecule CD11b and L-selectin.We carried out a series of experiments using donor blood from 30 healthy adult human volunteers. In all experiments, neutrophil cell surface expressions of CD11b and L-selectin were assayed immediately and serially up to 2 hours, using immune-fluorescence techniques and flow cytometry. Study 1: Effects of PVC were compared with glass and polystyrene (n = 5). Study 2: Blood was mixed with Plasma-lyte (Pl) (prime solution), Hartman solutions, albumin or not altered (control), n = 5. Study 3: The effects of changing pH of the Pl (control, neutralised and acidic solution, n = 5) were examined. Study 4: Haemodilution (undiluted, 1:1, 1:2, and 1:3, vol/vol, prime to blood, n = 5) was carried out using Pl and the subsequent changes in expressions of the adhesion molecules were analysed. Study 5: The combined effect of PVC and Pl was assessed (n = 5). Study 6: We evaluated the effect of increasing plasma water by adding sterile water to whole blood and compared it with control (n = 5).Study 1: PVC, similar to glass, caused more up-regulation of CD11b and down-regulation of L-selectin than polystyrene (238 and 162% vs. 68 increase of CD11b, P < 0.001; 89 and 95% vs. 16% decrease of L-selectin, P < 0.001). Study 2: Pl and Hartman solutions caused more up-regulation of CD11b and down-regulation of L-selectin compared to albumin and control (166 and 188% vs. 26 and 44% increase of CD11b, P < 0.01; 19 and 26% vs. 10 and 6% decrease of L-selectin, P < 0.01, respectively). Study 3: Haemodilution had no effect on these molecules. Study 4: The mean of the difference between the acidic and neutral solution was 208% increase of CD11b and 30% decrease of L-selectin, P < 0.05. Study 5: The combined effect of mixing blood with Pl and exposure to PVC caused marked up-regulation of CD11b (336% increase, P < 0.01) and down-regulation of L-selectin (78% decrease, P < 0.05). Study 6: Water for injection caused marked up-regulation of CD1 1b and down-regulation of L-selectin.Mixing blood with acidic prime solution and/or exposing it to PVC tubes causes up-regulation of neutrophil adhesion molecule CD11b and down-regulation of L-selectin. Neutralisation of the prime solution reduces the extent of neutrophil activation, whereas haemodilution has no effect. Increasing plasma water is stimulating to the neutrophil. Modulation of prime solutions and the material of CPB tubes may reduce neutrophil activation which may reduce patient morbidity.
Limitations of echocardiography in the assessment of left ventricular size and function in aortic regurgitation.
Authors: A M Abdulla, M J Frank, M I Canedo, M A Stefadouros
Journal: Circulation (1980)

The optimal timing for prosthetic valve replacement in patients with aortic regurgitation (AR) depends on the identification of left ventricular (LV) enlargement and dysfunction.Whether this goal could he achieved reliably by echocardiography was evaluated in 22 patients with pure or dominant AR (AR group) in whom echocardiographic LV dimensions and performance indices were compared with corresponding dimen- sion, volume and performance data obtained by single-plane and biplane angiography.Echocardiographic and single-plane angiographic comparisons were also made in 18 patients with diseases other than AR (non-AR group).
Marimastat in the Treatment of Patients with Biochemically Relapsed Prostate Cancer: A Prospective Randomized, Double-Blind, Phase I/II Trial
Authors: Eli Rosenbaum, Marianna Zahurak, Victoria Sinibaldi, Michael A. Carducci, Roberto Pili, Menachem Laufer, Theodore L. DeWeese, Mario A. Eisenberger
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To evaluate the safety and biological activity of three different doses of marimastat given for 6 months to patients with biochemically relapsed prostate cancer. Experimental Design: Patients with a biochemical relapse within 2 years of primary therapy, a prostate-specific antigen (PSA) increase of at least 50% within 6 months of study entry, and no prior systemic therapy were eligible. Patients were randomized to receive marimastat at total daily doses of 5, 20, or 40 mg for 6 months unless dose-limiting toxicity or new evidence of disease occurred. Results: Thirty-nine patients were treated. Grade 3-4 reversible musculoskeletal toxicity was the only dose-limiting toxicity. Increasing dose was associated with increased probability of experiencing dose-limiting toxicity (5.9%, 42.9% and 88.9% for the 5, 20, and 40 mg groups, respectively; P = 0.03). Accrual was discontinued early on the two higher dose levels due to toxicity. A significant decrease in PSA slope was shown in the 20 mg group when compared with the 5 mg group (0.117 and −0.0046, respectively; P = 0.03) The 40 mg group (versus the 5 mg group) showed a similar change (0.109) with a trend towards significance (P = 0.07). An increased serum matrix metalloproteinase 2 level at month 3 compared with the baseline correlated with a decrease in PSA slopes (Slope, 0.001; 95% confidence interval, 0.0002-0.0018; P = 0.02). Conclusion: These data suggest that marimastat has a biological effect and may effectively delay progression in patients with biochemical relapsed prostate cancer, as shown by the change in PSA slope; however, dose-limiting toxicity at active doses is significant. Confirmatory studies with less toxic matrix metalloproteinase inhibitors employing more conventional end points are indicated. This design is feasible and potentially efficient for screening antimetastatic agents.
Effect of Ganglionic Blocking Agents Upon Blood Flow and Resistance in the Superior Mesenteric Artery of the Dog
Authors: JOSEPH H. TRAPOLD, Joan G. Sullivan
Journal: Circulation Research (1956)

The response of the mesenteric vascular circuit of anesthetized dogs to a group of ganglionic blocking agents has been studied. The results demonstrate that these agents produce a decrease in blood pressure, blood flow and vasomotor activity of the mesenteric bed and either no change or a decrease in mesenteric resistance. When the perfusing pressure to the mesenteric artery was maintained at control levels an increase in flow with a concomitant decrease in mesenteric resistance followed the injection of the blocking agents. The present report presents experimental evidence that our preliminary report was in error.
Monitoring of Early Response to Neoadjuvant Chemotherapy in Stage II and III Breast Cancer by [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography
Authors: Caroline Rousseau, Anne Devillers, Christine Sagan, Ludovic Ferrer, Boumédiène Bridji, Loïc Campion, Myriam Ricaud, Emmanuelle Bourbouloux, Isabelle Doutriaux, Martine Clouet, Dominique Berton-Rigaud, Catherine Bouriel, Valérie Delecroix, Etienne Garin, Sophie Rouquette, Isabelle Resche, Pierre Kerbrat, Jean François Chatal, Mario Campone
Journal: Journal of Clinical Oncology (2006)

This study aimed to assess prospectively the efficacy of sequential [18F]fluorodeoxyglucose positron emission tomography (FDG PET) to evaluate early response to neoadjuvant chemotherapy in stage II and III breast cancer patients.Images were acquired with a PET/computed tomography scanner in 64 patients after administration of FDG (5 MBq/kg) at baseline and after the first, second, third, and sixth course of chemotherapy. Ultrasound and mammography were used to assess tumor size. Decrease in the standardized uptake value (SUV) with PET was compared with the pathologic response.Surgery was performed after six courses of chemotherapy and pathologic analysis revealed gross residual disease in 28 patients and minimal residual disease in 36 patients. Although SUV data did not vary much in nonresponders (based on pathology findings), they decreased markedly to background levels in 94% (34 of 36) of responders. When using 60% of SUV at baseline as the cutoff value, the sensitivity, specificity, and negative predictive value of FDG PET were 61%, 96%, and 68% after one course of chemotherapy, 89%, 95%, and 85% after two courses, and 88%, 73%, and 83% after three courses, respectively. The same parameters with ultrasound (US) and mammography were 64%, 43%, and 55%, and 31%, 56%, and 45%, respectively. Assessment of tumor response with US or mammography was never significant whatever the cutoff.Pathologic response to neoadjuvant chemotherapy in stage II and III breast cancer can be predicted accurately by FDG PET after two courses of chemotherapy.