tbuckley/cabot-search huggingface dataset:
Patient Quality of Life Safeguarding: The Primary Aim in Nonmetastatic Prostate Cancer Patients
Authors: Tommaso Cai, Riccardo Bartoletti
Journal: Journal of Clinical Oncology (2007)

TO THE EDITOR: It was with great interest that we read Michaelson et al’s article in the Journal of Clinical Oncology concerning the role of a single treatment with zolendronic acid to prevent gonadotropin-releasing hormone (GnRH) agonistinduced bone loss in men with nonmetastatic prostate cancer. In this well-set-out study, which showed that a single dose of zolendronic acid (4 mg once in 12 months) significantly increases bone mineral density (BMD) and durably suppresses biochemical markers of bone turnover, the authors highlighted a most important feature of nonmetastatic prostate cancer treatment (ie, the need for patient quality of life [QoL] safeguarding). Therefore, in patients affected by nonmetastatic prostate cancer, the preservation of patient QoL is an essential target because of the fact that this neoplasm often has nonaggressive biologic and clinical behavior. However, we would like to make an additional consideration regarding their study. The authors enrolled 44 patients (22 treated and 22 placebo), who had undergone GnRH agonist throughout the study with a different duration of prior GnRH agonist treatment of 21 17 months for the zoledronic acid group and 12 16 months for the placebo group. The authors, however, when explaining their study limitations, state that BMD decreases at a steady rate regardless of the duration of past GnRH agonist exposure, as reported by Lee et al. We would like to highlight the fact that a more rapid mineral bone mass reduction is associated with initial serum testosterone decreasing to castrate levels, due to a higher bone turnover, as reported by Greenspan et al. This aspect is crucial and well known in the bone mineral mass loss related to postmenopausal hormonal changes. Consequently, the question is since BMD reduction prophylaxis with a single dose of zolendronic acid is really useful in nonmetastatic prostate cancer patient QoL safeguarding, can it be useful to select the best time for administering this kind of treatment? On the basis of this well-presented study, we think that the fact should be stressed that early administration of zolendronic acid should be suggested in nonmetastatic prostate cancer patients treated with GnRH agonist, particularly to reduce the costs related to fracture due to GnRH agonist-induced osteoporosis.
Extracellular Adenosine Induces Apoptosis of Human Arterial Smooth Muscle Cells via A <sub>2b</sub> -Purinoceptor
Authors: Marie-Line Peyot, Alain-Pierre Gadeau, Frédéric Dandré, Isabelle Belloc, Françoise Dupuch, Claude Desgranges
Journal: Circulation Research (2000)

Apoptosis of arterial smooth muscle cells (ASMCs) could play an important role in the pathogenesis of atherosclerosis and restenosis. Recent studies have demonstrated that extracellular adenosine induces apoptosis in various cell types. Our aim was to delineate the capacity of this nucleoside to induce ASMC apoptosis in arterial diseases. We demonstrate that adenosine dose-dependently triggers apoptosis of cultured human ASMCs. Apoptotic cell death was quantified by analysis of nuclear chromatin morphology and characterized by DNA laddering. The involvement of adenosine receptors was suggested, because neither an adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride, nor an inhibitor of cellular nucleoside transport, dipyridamole, was able to inhibit adenosine-induced ASMC apoptosis. In contrast, an A(1)/A(2)-adenosine receptor antagonist, xanthine amine congener, totally inhibited adenosine-induced apoptosis. Furthermore, among more selective inhibitors of P(1) purinoceptor subtypes, only alloxazine, an antagonist of A(1)- and A(2)-adenosine receptors, completely inhibited adenosine-induced ASMC apoptosis, suggesting that adenosine triggers ASMC apoptosis via either 1 or both of these receptors. However, 8-cyclopentyl-1,3-dipropylxanthine, 8-(3-chlorostyryl) caffeine, and 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate, which are A(1)-, A(2a)-, and A(3)-adenosine receptor antagonists, did not inhibit adenosine-induced apoptosis, suggesting an involvement of the A(2b)-receptor in this process. Moreover, the cAMP increase followed by cAMP-dependent protein kinase activation appears essential to mediate adenosine-induced ASMC apoptosis, thus confirming the previous hypothesis. These results indicate that adenosine-induced apoptosis of ASMCs is essentially mediated via A(2b)-adenosine receptor and involves a cAMP-dependent pathway.
Probability of Cancer in Pulmonary Nodules Detected on First Screening CT
Authors: Annette McWilliams, Martin C. Tammemagi, John R. Mayo, Heidi Roberts, Geoffrey Liu, Kam Soghrati, Kazuhiro Yasufuku, Simon Martel, Francis Laberge, Michel Gingras, Sukhinder Atkar-Khattra, Christine D. Berg, Ken Evans, Richard Finley, John Yee, John English, Paola Nasute, John Goffin, Serge Puksa, Lori Stewart, Scott Tsai, Michael R. Johnston, Daria Manos, Garth Nicholas, Glenwood D. Goss, Jean M. Seely, Kayvan Amjadi, Alain Tremblay, Paul Burrowes, Paul MacEachern, Rick Bhatia, Ming-Sound Tsao, Stephen Lam
Journal: New England Journal of Medicine (2013)

Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up.We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer.In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set.Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).
Regulation of Renal Citrate Metabolism by Bicarbonate Ion and pH: Observations in Tissue Slices and Mitochondria*
Authors: David P. Simpson
Journal: Journal of Clinical Investigation (1967)

The effect of acid-base balance on the oxidation and utilization of citrate and other organic acids has been studied in tissue slices and isolated kidney mitochondria. The results show that: 1) With bicarbonate-buffered media, citrate oxidation and utilization are inhibited in slices of renal cortex and in kidney mitochondria when [HCO(3) (-)] and pH are increased within the physiologic range (pH 7.0 to 7.8; 10 to 60 mumoles HCO(3) (-) per ml). When phosphate or Tris buffers are used, no comparable effect on citrate oxidation occurs when pH is varied. 2) This effect is not demonstrable in heart or liver slices when a physiologic buffer is used. 3) alpha-Ketoglutarate utilization is inhibited in slices of renal cortex under similar conditions. Pyruvate and L-malate utilization are not inhibited in slices or mitochondria. 4) Citrate content in slices of renal cortex incubated with a high [HCO(3) (-)] is considerably greater than the concentration found with a low [HCO(3) (-)] in the medium. This effect is not duplicated by pH change in a nonbicarbonate buffer system. In mitochondria citrate content is also increased markedly at high bicarbonate concentrations. 5) The kinetic characteristics of the inhibition of citrate oxidation are those of a competitive type of inhibition. 6) When pH was varied with a constant [HCO(3) (-)] in the media, citrate oxidation was inhibited by increasing pH in slices of renal cortex but not in mitochondria. On the other hand, when [HCO(3) (-)] was increased without change in pH, no decrease in citrate oxidation occurred in slices, but a marked inhibitory effect was found when mitochondria were used. From a comparison of these results with those previously obtained in intact animal experiments, we conclude that the inhibition of citrate oxidation caused by increasing pH and [HCO(3) (-)] in slices of renal cortex and kidney mitochondria is an in vitro representation of the inhibition of citrate reabsorption in the nephron that occurs in metabolic alkalosis. Thus, citrate clearance increases in metabolic alkalosis because of inhibition of oxidation of reabsorbed citrate within cells of the renal tubules. This inhibition is the result of an inhibitory effect of bicarbonate ion on citrate oxidation in mitochondria.
Low-Density Lipoprotein Cholesterol and the Risk of Dementia With Stroke
Authors: Joan T. Moroney
Journal: JAMA (1999)

ContextNext to Alzheimer disease, vascular dementia is the second most common form of dementia in the elderly, yet few specific risk factors have been identified.ObjectiveTo investigate the relationship of plasma lipids and lipoproteins to dementia with stroke.Design and SettingProspective longitudinal community-based study over a 7-year period (1991-1998).ParticipantsA total of 1111 nondemented participants (mean [SD] age, 75.0 [5.9] years) were followed up for an average of 2.1 years (range, 1-7.8 years).Main Outcome MeasureIncident dementia with stroke according to standardized criteria, by baseline levels of total plasma cholesterol and triglycerides, low-density lipoprotein (LDL) cholesterol, LDL levels corrected for lipoprotein(a), high-density lipoprotein cholesterol, lipoprotein(a), and apolipoprotein E genotype.ResultsTwo hundred eighty-six (25.7%) of the 1111 subjects developed dementia during follow-up; 61 (21.3%) were classified as having dementia with stroke and 225 (78.7%) as having probable Alzheimer disease. Levels of LDL cholesterol were significantly associated with an increased risk of dementia with stroke. Compared with the lowest quartile, the highest quartile of LDL cholesterol was associated with an approximately 3-fold increase in risk of dementia with stroke, adjusting for vascular risk factors and demographic variables (relative risk [RR], 3.1; 95% confidence interval [CI], 1.5-6.1). Levels of LDL corrected for lipoprotein(a) were an even stronger predictor of dementia with stroke in the adjusted multivariate analysis. Compared with the lowest quartile, the RR of dementia with stroke for the highest quartile of lipoprotein(a)–corrected LDL cholesterol was 4.1 (95% CI, 1.8-9.6) after adjusting for vascular factors and demographic variables. Lipid or lipoprotein levels were not associated with the development of Alzheimer disease in our cohort.ConclusionsElevated levels of LDL cholesterol were associated with the risk of dementia with stroke in elderly patients. Further study is needed to determine whether treatment of elevated LDL cholesterol levels will reduce the risk of dementia with stroke.
Hypokalemic Nephropathy is Associated with Impaired Angiogenesis
Authors: Sirirat Reungjui, Carlos A. Roncal, Waichi Sato, Olena Y. Glushakova, Byron P. Croker, Shin-ichi Suga, Xiaosen Ouyang, Kriang Tungsanga, Takahiko Nakagawa, Richard J. Johnson, Wei Mu
Journal: Journal of the American Society of Nephrology (2008)

Hypokalemic nephropathy is associated with alterations in intrarenal vasoactive substances, leading to vasoconstriction, salt-sensitivity, and progression of interstitial fibrosis. In this study, we investigated whether hypokalemic nephropathy might also involve impaired renal angiogenesis. Sprague-Dawley rats that were fed low-potassium diets developed peritubular capillary loss that began in the inner stripe of the outer medulla (week 2) and progressed to the outer stripe of the outer medulla (week 4) and cortex (week 12). These changes were associated with increased macrophage infiltration, increased expression of both monocyte chemoattractant protein-1 and TNF-alpha, and a loss of vascular endothelial growth factor and endothelial nitric oxide synthase. Renal thiobarbituric acid-reactive substances, markers of oxidative stress, were increased late in disease. In conclusion, hypokalemic nephropathy is associated with impaired renal angiogenesis, evidenced by progressive capillary loss, reduced endothelial cell proliferation, and loss of VEGF expression.
Three-dimensional nonfluoroscopic mapping and ablation of inappropriate sinus tachycardia
Authors: Nassir F Marrouche, Salwa Beheiry, Gery Tomassoni, Christopher Cole, Dianna Bash, Thomas Dresing, Walid Saliba, Ahmad Abdul-Karim, Patrick Tchou, Robert Schweikert, Fabio Leonelli, Andrea Natale
Journal: Journal of the American College of Cardiology (2002)
Comparative study between hydrokinesio therapy and conventional physiotherapeutic modalities in perspective of rotator cuff impingement: a pilot study
Authors: Sandipan DasSarma, Anirban Mallick, Manabendra Bhattacharyya
Journal: British Journal of Sports Medicine (2010)

Hydrokinesio therapy means active physical rehabilitation modality with the help of buoyancy, relative density, resistance and turbulence of water in swimming pool or tub. The aim was to evaluate the effect of the said therapy over conventional physiotherapeutic modalities, for example, mobilisation, manipulation in the cases of rotator cuff impingement. Twenty cases (10 males, 10 females with a mean age of 20 years) of rotator cuff impingements of different aetiologies with duration of pain of 8–12 weeks were divided arbitrarily into two groups. Modified DASH and ASES questionnaire were used to define pain perception and improvement. Goniometer was used to measure the pain-free range of movement. One of the groups (group A) was given different conventional physiotherapeutic modalities for 6 days a week (once daily) for 3 weeks and was compared against hydrokinesio therapy (group B) protocol (aquatic PNF, bad ragaz ring method, water pilates) once daily for 45 min for 3 weeks. Data were analysed statistically by means of improvement in range of motion of the affected shoulder joint and pain perception. p Value &lt; 0.05 was taken as statistically significant. Eight patients (group B) were satisfied with hydrokinesio therapy. Their DASH score was decreased 25 ± 5 whereas in group A the reduction was 15±6. Moreover, cases of group B showed significant improvement in painless range of motion (30° ± 5°), compared with group A (18° ± 4°). It can be suggested that being an active modality the said hydrokinesio therapy is showing significant patient benefit compared with conventional treatment.
Stat-3 is required for pulmonary homeostasis during hyperoxia
Authors: Isamu Hokuto, Machiko Ikegami, Mitsuhiro Yoshida, Kiyoshi Takeda, Shizuo Akira, Anne-Karina T. Perl, William M. Hull, Susan E. Wert, Jeffrey A. Whitsett
Journal: Journal of Clinical Investigation (2004)

Acute lung injury syndromes remain common causes of morbidity and mortality in adults and children. Cellular and physiologic mechanisms maintaining pulmonary homeostasis during lung injury remain poorly understood. In the present study, the Stat-3 gene was selectively deleted in respiratory epithelial cells by conditional expression of Cre-recombinase under control of the surfactant protein C gene promoter. Cell-selective deletion of Stat-3 in respiratory epithelial cells did not alter prenatal lung morphogenesis or postnatal lung function. However, exposure of adult Stat-3–deleted mice to 95% oxygen caused a more rapidly progressive lung injury associated with alveolar capillary leak and acute respiratory distress. Epithelial cell injury and inflammatory responses were increased in the Stat-3–deleted mice. Surfactant proteins and lipids were decreased or absent in alveolar lavage material. Intratracheal treatment with exogenous surfactant protein B improved survival and lung histology in Stat-3–deleted mice during hyperoxia. Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury.
Docetaxel and Cisplatin in Combination as First-Line Chemotherapy for Advanced Epithelial Ovarian Cancer
Authors: P. A. Vasey, J. Paul, A. Birt, E. J. Junor, N. S. Reed, R. P. Symonds, R. Atkinson, J. Graham, S. M. Crawford, R. Coleman, H. Thomas, J. Davis, S. P.H. Eggleton, S. B. Kaye
Journal: Journal of Clinical Oncology (1999)

PURPOSE: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m2 and docetaxel 75 mg/m2); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m2 and docetaxel 85 mg/m2). RESULTS: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION: Cisplatin and docetaxel can be administered at doses of 75 mg/m2 and 75 mg/m2, respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m2 adds unacceptable hematologic toxicity and potential risks to the patient.
A comprehensive assessment of satisfaction with care: Preliminary psychometric analysis in an oncology institute in Italy
Authors: A. Brédart, D. Razavi, C. Robertson, F. Didier, E. Scaffidi, J.C.J.M. de Haes
Journal: Annals of Oncology (1999)

Little is known about patients' perception of the quality of the care they receive in oncology hospitals. We developed a 61-item comprehensive assessment of satisfaction with care (CASC) to evaluate the competence of hospital physicians and nurses, as well as aspects of care organisation and hospital environment. The aims of this study were to define the structure of the CASC and assess the internal consistency and convergent and discriminant validity of its scales.Three hundred ninety-five consecutive cancer patients discharged from an oncology institute in Italy were asked to complete the CASC at home and return it in a self-addressed envelope.Two percent of the patients refused to participate and 25% failed to return the questionnaire. Separate factor analyses of the CASC sub-scales disclosed the perceived extent of doctors' and nurses' availability, coordination, human quality, technical competence, provision of psychosocial care and information, as well as the patients' general satisfaction, perception of the organisation of their care, access and comfort. Multi-trait scaling analysis was carried out on item-grouping resulting from factor analyses. High levels of internal consistency and convergent validity were obtained but discriminant validity could be improved.Results of present psychometric testing of the CASC forecast adequate properties. This will be confirmed by repeating these analyses in a cross-cultural setting.
Desensitization Therapy in Impotence and Frigidity: Review of the Literature and Report of a Case
Authors: BURTON S. GLICK
Journal: American Journal of Psychiatry (1975)

The author reviews the available scientific literature on the use of behavior therapy in the treatment of impotence and frigidity, noting that there is a dearth of published information in this area. Behavioral techniques are described, and a case of impotence and anhedonia that responded well to relaxation/desensitization therapy is presented. The author concludes on the basis of his clinical experience and review of the literature that desensitization has definite value in the treatment of impotence and frigidity.
Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma
Authors: Elizabeth K Sage, Krishna K Kolluri, Katrina McNulty, Sofia Da Silva Lourenco, Tammy L Kalber, Katherine L Ordidge, Derek Davies, Y C Gary Lee, Adam Giangreco, Sam M Janes
Journal: Thorax (2014)

Malignant pleural mesothelioma is a rare but devastating cancer of the pleural lining with no effective treatment. The tumour is often diffusely spread throughout the chest cavity, making surgical resection difficult, while systemic chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate into tumour stroma, making them good candidates to deliver anticancer therapies. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic molecule that selectively induces apoptosis in cancer cells, leaving healthy cells unaffected. We hypothesised that human MSCs expressing TRAIL (MSCTRAIL) would home to an in vivo model of malignant pleural mesothelioma and reduce tumour growth. Human MSCs transduced with a lentiviral vector encoding TRAIL were shown in vitro to kill multiple malignant mesothelioma cell lines as predicted by sensitivity to recombinant TRAIL (rTRAIL). In vivo MSC homing was delineated using dual fluorescence and bioluminescent imaging, and we observed that higher levels of MSC engraftment occur after intravenous delivery compared with intrapleural delivery of MSCs. Finally, we show that intravenous delivery of MSCTRAIL results in a reduction in malignant pleural mesothelioma tumour growth in vivo via an increase in tumour cell apoptosis.
Discrimination and Net Reclassification of Cardiovascular Risk With Lipoprotein(a)
Authors: Peter Willeit, Stefan Kiechl, Florian Kronenberg, Joseph L. Witztum, Peter Santer, Manuel Mayr, Qingbo Xu, Agnes Mayr, Johann Willeit, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2014)