tbuckley/cabot-search huggingface dataset:
Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. The Aredia Multinational Cooperative Group.
Authors: P F Conte, J Latreille, L Mauriac, F Calabresi, R Santos, D Campos, J Bonneterre, G Francini, J M Ford
Journal: Journal of Clinical Oncology (1996)

PURPOSE Bone metastases are a major cause of morbidity in breast cancer, resulting in complications that include pain, loss of mobility, pathologic fracture, and tumor-induced hypercalcemia (TIH). Inhibition of osteoclast-mediated bone destruction using bisphosphonates represents a promising new management approach. PATIENTS AND METHODS Breast cancer patients with bone metastases were randomly allocated to receive chemotherapy alone (152 patients) or chemotherapy plus pamidronate 45 mg in 250 mL of saline as a 1-hour intravenous infusion every 3 weeks (143 patients). Whenever possible, treatment continued until progression of disease (PD) in bone appeared on radiographs or bone scan. Time to PD in bone and pain reduction according to a self-assessment six-point scale were selected as primary end points. PD in bone was verified during extramural review (EMR) of all imaging studies by blinded observers, and these data were used as the main efficacy criterion. Analgesic intake, World Health Organization (WHO) performance status, and complications of bone metastases (radiotherapy, TIH, fractures, orthopedic surgery) were also compared in the two groups. RESULTS AND CONCLUSION At EMR, median time to PD in bone was increased by 48% in patients who received pamidronate (249 v 168 days; P = .02, Wilcoxon test). Marked pain relief, defined as a two-point decrease lasting for &gt; or = 6 weeks, was reported by 44% of pamidronate patients and by 30% of controls (P = .025, chi 2 test). The infusions (median, nine per patient; range, 0 to 39) were well tolerated, with no major toxicities reported. Pamidronate by repeated infusion can significantly slow the progression of bone metastases and reduce attendant morbidity.
Suppression of the Immune Response in Tumor-Bearing Mice. I. Response to Virus-Producing Tumor Cells and Non-Virus-Producing Tumor Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J A Bluestone, C Lopez
Journal: JNCI Journal of the National Cancer Institute (1979)

Spleen cells from mice inoculated with syngeneic murine sarcoma virus (MuSV)-transformed tumor cells suppressed the mixed leukocyte reaction. Mice inoculated with virus-producing tumor cells demonstrated two types of suppression. First, an early suppression was shown to be mediated by an adherent suppressor T-cell on the basis of its sensitivity to Thy 1.2 antiserum plus complement and the absence of the early suppression In T-cell-deficient nude mice. This suppression may have been Induced In response to viral antigens associated with cell surface antigens (modified self-antigens) or viremia, because It was not induced by a non-virus-producing tumor cell line. Second, a late suppression was also seen In tumor-bearing BALB/c mice. This suppression was shown to be T-cell-independent by its presence in nude mice and by its resistance to γ-irradiation and Thy 1.2 antiserum plus complement. In addition, the late suppression was present in mice inoculated with a non producer clone of MuSV-transformed cells. This finding suggests that viral antigens and/or viremia I. not required for induction of the late suppression.
The Use of Household Cleaning Sprays and Adult Asthma
Authors: Jan-Paul Zock, Estel Plana, Deborah Jarvis, Josep M. Antó, Hans Kromhout, Susan M. Kennedy, Nino Künzli, Simona Villani, Mario Olivieri, Kjell Torén, Katja Radon, Jordi Sunyer, Anna Dahlman-Hoglund, Dan Norbäck, Manolis Kogevinas
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Cleaning work and professional use of certain cleaning products have been associated with asthma, but respiratory effects of nonprofessional home cleaning have rarely been studied.Objectives: To investigate the risk of new-onset asthma in relation to the use of common household cleaners.Methods: Within the follow-up of the European Community Respiratory Health Survey in 10 countries, we identified 3,503 persons doing the cleaning in their homes and who were free of asthma at baseline. Frequency of use of 15 types of cleaning products was obtained in a face-to-face interview at follow-up. We studied the incidence of asthma defined as physician diagnosis and as symptoms or medication usage at follow-up. Associations between asthma and the use of cleaning products were evaluated using multivariable Cox proportional hazards or log-binomial regression analysis.Measurements and Main Results: The use of cleaning sprays at least weekly (42% of participants) was associated with the incidence of asthma symptoms or medication (relative risk [RR], 1.49; 95% confidence interval [CI], 1.12−1.99) and wheeze (RR, 1.39; 95% CI, 1.06−1.80). The incidence of physician-diagnosed asthma was higher among those using sprays at least 4 days per week (RR, 2.11; 95% CI, 1.15−3.89). These associations were consistent for subgroups and not modified by atopy. Dose–response relationships (P < 0.05) were apparent for the frequency of use and the number of different sprays. Risks were predominantly found for the commonly used glass-cleaning, furniture, and air-refreshing sprays. Cleaning products not applied in spray form were not associated with asthma.Conclusions: Frequent use of common household cleaning sprays may be an important risk factor for adult asthma.
Clinafloxacin monotherapy (CI-960) versus ceftazidime plus amikacin for empirical treatment of febrile neutropenic cancer patients
Authors: M.P. Glauser, U. Brennscheidt, O. Cornely, A. Grigg, A. Figuera, C. Keyserling, U. Trostmann, L. Welling, K. Tack
Journal: Clinical Microbiology and Infection (2002)
Dose escalation of cyclophosphamide in patients with breast cancer: consequences for pharmacokinetics and metabolism.
Authors: D Busse, F W Busch, F Bohnenstengel, M Eichelbaum, P Fischer, J Opalinska, K Schumacher, E Schweizer, H K Kroemer
Journal: Journal of Clinical Oncology (1997)

PURPOSE The alkylating anticancer agent cyclophosphamide (CP) is a prodrug that undergoes a complex metabolism in humans producing both active and inactive metabolites. In parallel, unchanged CP is excreted via the kidneys. The aim of this study was to investigate the influence of dose escalation on CP pharmacokinetics and relative contribution of activating and inactivating elimination pathways. PATIENTS AND METHODS Pharmacokinetics of CP were assessed in 12 patients with high-risk primary breast cancer who received an adjuvant chemotherapy regimen that included four courses of conventional-dose CP (500 mg/m2 over 1 hour every 3 weeks) followed by one final course of high-dose CP (100 mg/kg over 1 hour). Plasma concentrations of CP were analyzed by high-performance liquid chromatography (HPLC), 24-hour urinary concentrations of CP, and its inactive metabolites (carboxyphosphamide, dechloroethylcyclophosphamide [dechlorethylCP], ketocyclophosphamide [ketoCP]) were determined by 31-phosphorus-nuclear magnetic resonance (31P-NMR)-spectroscopy. RESULTS There was no difference in dose-corrected area under the concentration-time curve (AUC) (216 v 223 [mumol.h/[mL.g]), elimination half-life (4.8 v 4.8 hours), systemic clearance (79 v 77 mL/min) and volume of distribution (0.49 v 0.45 L/kg) of CP between conventional- and high-dose therapy, respectively. However, during high-dose chemotherapy, we observed a significant increase in the renal clearance of CP (15 v 23 mL/min; P &lt; .01) and in the formation clearance of carboxyphosphamide (7 v 12 mL/min; P &lt; .05) and dechloroethylCP (3.2 v 4.2 mL/min; P &lt; .05), whereas metabolic clearance to ketoCP remained unchanged (1.3 v 1.2 mL/min). Consequently, metabolic clearance to the remaining (reactive) metabolites decreased from 52 to 38 mL/min (P &lt; .001). The relative contribution of the different elimination pathways to overall clearance of CP demonstrated wide interindividual variability. CONCLUSION Overall pharmacokinetics of CP are apparently not affected during eightfold dose escalation. However, there is a shift in the relative contribution of different clearances to systemic CP clearance in favor of inactivating elimination pathways, thereby indicating saturation of bioactivating enzymes during dose escalation. Besides individual enzyme capacity, hydration and concomitant medication with dexamethasone modulated CP disposition.
Impact of Age and Sex on Response to Asthma Therapy
Authors: Ryan M. Dunn, Erik Lehman, Vernon M. Chinchilli, Richard J. Martin, Homer A. Boushey, Elliot Israel, Monica Kraft, Stephen C. Lazarus, Robert F. Lemanske, Njira L. Lugogo, Stephen P. Peters, Christine A. Sorkness, Stanley Szefler, Michael E. Wechsler
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Age and sex are associated with differences in asthma prevalence and morbidity.To determine if age and sex associate with distinct phenotypes and a variable response to therapy in subjects with mild to moderate asthma.We used Asthma Clinical Research Network data to determine the impact of age and sex on phenotypes and treatment failures among subjects participating in 10 trials from 1993 to 2003.A total of 1,200 subjects were identified (median age, 30.4 yr; male, 520 [43.3%]; female, 680 [56.7%]) and analyzed. A higher proportion of subjects greater than or equal to 30 years old experienced treatment failures (17.3% vs. 10.3%; odds ratio [OR], 1.82; confidence interval [CI], 1.30-2.54; P < 0.001), and rates increased proportionally with increasing age older than 30 across the cohort (OR per yr, 1.02 [CI, 1.01-1.04]; OR per 5 yr, 1.13 [CI, 1.04-1.22]; P < 0.001). Lower lung function and longer duration of asthma were associated with a higher risk of treatment failures. A higher proportion of subjects greater than or equal to 30 years old receiving controller therapy experienced treatment failures. When stratified by specific therapy, treatment failures increased consistently for every year older than age 30 in subjects on inhaled corticosteroids (OR per year, 1.03; CI, 1.01-1.07). Females had a slightly higher FEV1 % predicted (84.5% vs. 81.1%; P < 0.001) but similar asthma control measures. There was not a statistically significant difference in treatment failures between females and males (15.2% vs. 11.7%; P = 0.088).Older age is associated with an increased risk of treatment failure, particularly in subjects taking inhaled corticosteroids. There was no significant difference in treatment failures between sexes.
Antigenic Specificity of Hepatomas Induced in Strain-2 Guinea Pigs by Diethylnitrosamine
Authors: Berton Zbar, Harold T. Wepsic, Herbert J. Rapp, Tibor Borsos, Barry S. Kronman, Winthrop H. Churchill
Journal: JNCI Journal of the National Cancer Institute (1969)

The antigenic specificity of six hepatomas, each induced in a different strain-2 guinea pig by diethylnitrosamine, was studied. Five of six transplantable hepatomas were shown to be antigenic by their ability to induce delayed skin reactions or suppression of tumor growth. Two of these five tumor lines (1 and 8) shared common antigens; the other three initially lacked these antigens and were individually specific. After a number of transplant generations, two of the antigenically specific tumor lines acquired antigens common with line 1. The antigenicity of a chemically induced hepatoma (line 1) and a viral-induced leukemia was compared. Line 1 did not share antigens with this strain-2 leukemia.
Comparison of prevalence of diabetes mellitus in patients with idiopathic pulmonary arterial hypertension and distal chronic thromboembolic pulmonary hypertension
Authors: Charaka Hadinnapola, Carmen Treacy, Colm McCabe, Theodore Birks, Nicholas Morrell, Joanna Pepke Zaba
Journal: European Respiratory Journal (2013)

Increased prevalence of diabetes mellitus (DM) in idiopathic pulmonary arterial hypertension (IPAH) has been described. It is also known to be a risk factor for acute venous thromboembolism. Distal chronic thromboembolic pulmonary hypertension (dCTEPH) shares histological features with IPAH. We compared the prevalence of DM in IPAH and dCTEPH.

The Papworth Pulmonary Vascular Diseases Unit database identified patients with IPAH and dCTEPH from 01/01/2006 to 31/12/2012. Baseline characteristics at diagnosis were recorded.

View this table:

Baseline characteristics





The prevalence of DM was significantly lower in the dCTEPH group compared to the IPAH group, despite the group being older and having similar BMIs.

Limitations of this study are retrospective data collection and small population size. Within these limitations the prevalence of DM was lower in the dCTEPH group and higher in the IPAH group compared to the national prevalence (7.9%). The other characteristics are similar to published registries.

The different phenotypes suggest distinct risk factors are involved in these conditions that otherwise share many pathobiological processes. Our findings are preliminary and need to be confirmed in a bigger cohort including patients with proximal CTEPH.
Role of lobectomy in cystic fibrosis
Authors: Shahid Sheikh, Judy Pitts, Nancy Ryan-Wenger, Alpa Patel, Karen Mccoy
Journal: European Respiratory Journal (2013)

Patients with cystic fibrosis (CF) have progressive lung disease. A small proportion of CF patients develop localized destruction of the lung and some may develop recurrent hemoptysis or pneumothorax. Objective: To evaluate the usefulness of lung resection in patients with CF and either worsening localized lung disease or recurrent hemoptysis/pneumothorax. Methods: After local IRB approval, we reviewed charts of all patients with CF followed at the CF Center at Nationwide Children’s Hospital, Columbus, OH, who underwent lobectomy over the last 15 years (1995-2010). Patients who were followed for at least one year before surgery were included in this study.  Results: Among our cohort of CF patients (n=520), 15 patients were included in this report. Median age 20 years (range 2- 41), 93% Caucasian. Mean %FEV1 was 57%. Four patients died and all had mean %FEV1   In the total cohort, there were no significant changes in mean height, weight, BMI, number of hospital and ED visits, or oral and IV antibiotic use over time but within the group with %FEV1>40%, the number of hospital admissions decreased over time (1.5 vs. 0.5, p=.02). Mean % predicted FEV1 decreased over time but the rate of decline in % FEV1 decreased significantly during the second year post-surgery compared to during the first year post-surgery (p=0.007) in patients with less severe disease (%FEV1 40%. Poor outcomes or lack of clinical improvement are associated with %FEV1
Mammary Nodules in Beagle Dogs Administered Investigational Oral Contraceptive Steroids 2 3
Authors: R. C. Giles, R. P. Kwapien, R. G. Geil, H. W. Casey
Journal: JNCI Journal of the National Cancer Institute (1978)

Of 172 beagle dogs administered oral contraceptive steroids for 5-7 years, 114 developed 1,156 nodules in the mammary gland region. Most of these nodules arose 2.5-3.5 years after initiation of treatment. Approximately 16% of the nodules were transient and disappeared spontaneously from the mammary gland during the study. A total of 925 nodules were present in 99 dogs at the time of death or necropsy. These nodules were classified as benign mammary dysplasias (7.0%), lobular or intraductal hyperplasias (31.4%), simple adenomas (20.8%), complex adenomas (25.4%), benign mixed tumors (5.3%), malignant tumors (3.6%), or nonmammary lesions (6.5%). Histologically, the mammary nodules were representative primarily of the hyperplasias and tumors that occur spontaneously in the mammary glands of the dog. The only major exception was the presence of 82 simple adenomas that had basaloid features. Most of the contraceptive-related mammary nodules developed in dogs receiving the combination of progestion and mestranol at 10 or 25 times the proposed human dosage. Control dogs and dogs receiving mestrenol alone had few mammary nodules. Combinations of anagestone acetate and mestranol and chloroethynyl norgestrel (WY-4355) and mestranol produced large numbers of nodules at 10 and 25 times the proposed human dosage, whereas ethynerone plus mestranol produced large numbers of nodules only at 25 times the proposed human dosage. Ethynerone, when given alone at 25 times the proposed human dosage, was associated with fewer mammary nodules. Malignant neoplasms were seen in dogs given 10 and 25 times the proposed human dosage of anagestone acetate plus mestranol and 25 times the proposed human dosage of WY-4355 plus mestranol and ethynerone plus mestranol. This study strongly associates certain combinations of progestin and mestranol with mammary neoplasia in dogs.
Colon Cancer and Dietary Fat, Phosphate, and Calcium: A Hypothesis
Authors: H. L. Newmark, Michael J Wargovich, W. R. Bruce
Journal: JNCI Journal of the National Cancer Institute (1984)

Increased dietary fat was suggested to promote colon cancer by increasing the levels of free ionized fatty acids and bile acids in the colon contents. In the presence of calcium ions the irritating and toxic effects of the free acids on colon epithelial cells could be reduced by being converted to insoluble calcium soaps. The level of supplementary dietary calcium to supply adequate calcium and thus reduce the potential toxicity of dietary fat was considered.
Effect of dietary mineral salt on blood pressure
Authors: H Fielder, S Vuilo, J M Geleijnse, J C M Witteman, D E Grobbee
Journal: BMJ (1994)

Peptic ulceration has always been a clear contraindication to working on an offshore installation, and ready access to H2 antagonists over the counter would have two consequences: firstly, people would treat symptoms without a definitive diag- nosis being made, and, secondly, people would not take the drug properly even when the treatment was correct.These facts would increase the risks of employees continuing to work offshore with undiagnosed or masked peptic ulceration.The incidence ofmedical evacuations for gastrointestinal emergencies is not insignificant, and if the patient is in the remoter regions of the North Sea, for example, evacuation may result in considerable danger to the many people involved.
Antitumor Effect of a Copper Coordination Compound With Superoxide Dismutase-Like Activity2
Authors: Susan W. C. Leuthauser, Larry W. Oberley, Terry D. Oberley, John R. J. Sorenson, K. Ramakrishna
Journal: JNCI Journal of the National Cancer Institute (1981)

Growth of Ehrlich carcinomas in inbred CBA mice was retarded by im administration of Cu(II)(3,5-diisopropylsalicylate)2 (CuDIPS). CuDIPS is a low molecular weight (mol wt = 503) copper coordination compound that exhibits superoxide dismutase (SOD)-like activity. It has been used as an anti-inflammatory agent and is lipid-soluble. This property enables the compound to penetrate membranes, thus becoming an intracellular O2- scavenger. In the tumor system studied, the amounts of both copper- and zinc-containing SOD (CuZnSOD) and manganese-containing SOD are reduced. Injection of Orgotein (CuZnSOD from bovine liver) had no significant effect on tumor growth and host survival. When CuDIPS was administered at various doses, reduction in tumor size, delay of metastasis, and a significant increase in survival of the hosts were observed.
Nuclear Aberrations As a Short-Term Test for Genotoxicity to the Colon: Evaluation of Nineteen Agents In Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Michael J Wargovich, M. T. Goldberg, H. L. Newmark, W. R. Bruce
Journal: JNCI Journal of the National Cancer Institute (1983)

The genotoxicity of 16 agents including several hydrazines, nitrosamines, aromatic amines, polycyclic hydrocarbons, and other related compounds and three known inhibitors of carcinogenesis was assessed in the murine colonic nuclear aberration assay. Of the seven agents considered positive for colonic DNA damage, five were large bowel carcinogens. All structural analogues of the intestinal carcinogens that are tumorigenic for other organs, with the exception of benzo[a]pyrene, were negative in the colonic nuclear aberration assay as were all noncarcinogens tested. The metabolic inhibitor disulfiram completely inhibited 1,2-dimethylhydrazine-induced colonic nuclear damage, while inhibition was less marked for the antioxidants butylated hydroxyanisole and caffeic acid. The versatility of the assay as an indicator of colonic genotoxicity resulting from carcinogen exposure is discussed.
Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients.
Authors: P Ruffie, R Feld, S Minkin, Y Cormier, A Boutan-Laroze, R Ginsberg, J Ayoub, F A Shepherd, W K Evans, A Figueredo
Journal: Journal of Clinical Oncology (1989)

Three-hundred thirty-two cases of pleural diffuse malignant mesothelioma (DMM) seen at large centers in Ontario and Quebec from 1965 to 1984 were reviewed retrospectively. Previous asbestos exposure was found in 44% of patients. Diagnosis was most often made by exploratory thoracotomy; pleural biopsy or cytology were rarely contributory. The delay in diagnosis was often long (median time, 3.5 months) and thrombocytosis (platelets greater than or equal to 400,000/microL) was common (41% of cases). The median survival (MS) was only 9 months. Eleven clinical variables were analyzed for prognostic significance. The three most important prognostic factors using a univariate analysis were stage, weight loss, and histologic type. For 118 patients with complete data, multivariate analysis showed that the stage of disease, high platelet count, and asbestos exposure were the most important prognostic factors. There was no cure of DMM, and we did not find any drastic differences in survival among groups of patients subjected to the different therapeutic measures. Radical surgery and radiotherapy were ineffective and we confirmed the low response rate to chemotherapeutic agents. This large retrospective trial can serve as a baseline for future studies in this field. In particular, it provides the basis for appropriate stratification variables to be used in future therapeutic trials.
Immune Mechanisms in Arterial Hypertension
Authors: Ulrich Wenzel, Jan Eric Turner, Christian Krebs, Christian Kurts, David G. Harrison, Heimo Ehmke
Journal: Journal of the American Society of Nephrology (2015)

Traditionally, arterial hypertension and subsequent end-organ damage have been attributed to hemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign organisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Renal inflammation results in injury and impaired urinary sodium excretion, and vascular inflammation leads to endothelial dysfunction, increased vascular resistance, and arterial remodeling and stiffening. Notably, modulation of the immune response can reduce the severity of BP elevation and hypertensive end-organ damage in several animal models. Indeed, recent studies have improved our understanding of how the immune response affects the pathogenesis of arterial hypertension, but the remarkable advances in basic immunology made during the last few years still await translation to the field of hypertension. This review briefly summarizes recent advances in immunity and hypertension as well as hypertensive end-organ damage.