tbuckley/cabot-search huggingface dataset:
Simultaneous analysis of clinical markers for predicting increased lung function fluctability in stable asthma
Authors: Kazuto Matsunaga, Atsushi Hayata, Tsunahiko Hirano, Masakazu Ichinose
Journal: European Respiratory Journal (2012)

Background: Airway hyperresponsiveness (AHR) has been shown to be associated with the loss of asthma control. Predicting the increased fluctuation of lung function might be useful to regulate the future risk of poor asthma control because peak expiratory flow (PEF) variability well correlates with AHR. Objective: We simultaneously analyzed the clinical markers for predicting increased PEF variability in stable asthma. Methods: We studied non-smoking asthmatic patients who were receiving conventional therapy and clinically stable for 8 weeks. Patient medical records were obtained and asthma control questionnaire (ACQ), spirometry, and exhaled nitric oxide fraction (FENO) were measured. Associations between these variables and PEF variability over a week (Min%Max) were prospectively assessed. Results: 52 of 297 asthmatics (17.5%) showed the increased PEF variability (Min%Max < 80%). These subjects were receiving more intensive therapy, but had more severe asthma symptoms, more airflow obstruction, and more evidence of airway inflammation. Especially, ACQ, forced expiratory volume in one second % of predicted (%FEV1), and FENO were identified to be independent predictors of Min%Max < 80%. When we combine baseline %FEV1 ≤ 85% and/or FENO ≥ 40 ppb, this index was associated with the highest combination of sensitivity (94.2%) and specificity (80.4%) for increased PEF variability. Conclusions: These results suggested that ACQ, %FEV1 and FENO can stratify risk for increased fluctuation of lung function among the clinically stable asthmatics.
NHS received almost 4000 written complaints every week last year
Authors: Adrian O’Dowd
Journal: BMJ (2015)

Complaints to the NHS in England seem to be rising and reached almost 4000 every week of last year (2014-15), new data from the Health and Social Care Information Centre have shown.1

The annual report is a count of written complaints made by or on behalf of patients and received from 1 April 2014 to 31 March 2015. The centre’s statistics showed that 205 289 written complaints were made to the NHS in 2014-15 overall, the equivalent of more than 3900 complaints a week …
Dynamic Hyperinflation with Bronchoconstriction
Authors: Tim J. T. Sutherland, Jan O. Cowan, D. Robin Taylor
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Symptoms and respiratory function tests may be difficult to assess and interpret in obese patients with asthma, particularly if the asthma is severe. It is unclear whether the dynamic changes that occur during bronchoconstriction differ between obese versus nonobese patients with asthma.To explore whether the changes in airway caliber and lung volumes that occur with acute bronchoconstriction are different in obese and nonobese patients with asthma and whether any differences contribute to the quality and intensity of symptoms.Thirty female patients with asthma were studied. Spirometry, lung volume measurements, and dyspnea scores were obtained before and immediately after bronchoconstriction induced by methacholine, aiming to provoke a reduction in FEV1 of 30%.Body mass index was independently associated with changes in lung volume after adjustment for baseline airway caliber and hyperresponsiveness. Increases in functional residual capacity and decreases in inspiratory capacity were significantly greater in obese participants (P < 0.001 and P = 0.003, respectively).Changes in respiratory function, notably dynamic hyperinflation, are greater in obese individuals with bronchoconstriction. This may potentially alter the perception and assessment of asthma severity in obese patients with asthma.
The impact of dyspnea on exercise capacity, physical activity in daily life, and health-related quality of life in adult subjects with non-cystic fibrosis bronchiectasis
Authors: Samia Zahi Rached, Rodrigo Athanazio, Anderson Alves de Camargo, Tatiane Soares Amaral, Fernanda de Cordoba Lanza, Dirceu Costa, Alberto Cukier, Regina Carvalho-Pinto, Celso Ricardo Fernandes Carvalho, Rafael Stelmach, Simone Dal Corso
Journal: European Respiratory Journal (2013)

Introduction: Dyspnea is a common finding in adult subjects with non-cystic fibrosis bronchiectasis (nCF-BCt), but its impact on exercise tolerance, physical activity in daily life (PADL), and health-related quality of life (HRQoL) has never been studied in these subjects.  Objective: To evaluate the impact of dyspnea on exercise tolerance, PADL, and HRQoL in adult subjects with nCF-BCt.  Methods: Eighty subjects (50 women) were evaluated in terms of dyspnea level, measured according to the Medical Research Council (MRC) scale. Exercise tolerance was evaluated by distance walked in the incremental shuttle walking test (ISWT), and peak workload by cardiopulmonary exercise testing. PADL was represented by the number of steps taken daily, measured by a pedometer, and HRQoL was assessed by St. George9s Respiratory Questionnaire (SGRQ). Spirometry was also performed.  Results: Results are shown in Table 1.  Conclusion: The higher the dyspnea level, the worst the pulmonary function, exercise tolerance, PADL, and HRQoL in adult subjects with nCF-BCt.
Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma.
Authors: J R Quesada, A Rios, D Swanson, P Trown, J U Gutterman
Journal: Journal of Clinical Oncology (1985)

Fifty-six patients with metastatic renal cell carcinoma (RCC) were treated with recombinant DNA-derived interferon alpha (rIFN alpha A). The first 30 patients were randomized between doses of 2 X 10(6) U/m2 and 20 X 10(6) U/m2 intramuscularly daily. No complete (CR) or partial (PR) remissions were achieved in 15 patients receiving the low dose. In contrast, 27% of those receiving the high dose achieved CR or PR. Subsequently, 26 additional patients were given the high dose and achieved a 31% response rate. Remissions lasted from 1 to more than 12 months (median, 3 months). Responses occurred predominantly in lung parenchyma or mediastinal node metastases. Toxicity of the high dose required dose reduction in 50% of the patients. Neutralizing antibodies to rIFN alpha A developed in seven of 12 responsive (58%) and nine of 29 (31%) nonresponsive patients (P = greater than .5). The median duration of remission among the antibody-positive and antibody-negative patients were 2 and 10 months, respectively (P = .009). The clinical significance of the antibodies to rIFN alpha A remains unclear, but the coincidence between the detection of antibodies and the early relapse of the disease in some responsive patients suggests that these antibodies may abrogate the biologic activity of rIFN alpha A. This effect, however, was not associated with adverse clinical sequelae.
Incorporation of 17β-Estradiol-6,7-&lt;sup&gt;3&lt;/sup&gt;H Into the Anterior Pituitary Gland of Rats Bearing a Hormone-Secreting Pituitary Tumor&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Thomas E. Williams, Robert M. MacLeod
Journal: JNCI Journal of the National Cancer Institute (1970)

Female Buffalo rats were implanted subcutaneously with a prolactin- and adrenocorticotropin-secreting pituitary tumor, 7315a, and were ovariectomized-adrenalectomized or ovariectomized 3–6 weeks later. The rats were inoculated once intraperitoneally or intravenously with 0.1 μg 17β-estradiol-6,7-3H/100 g body weight 4 days or 5 weeks after endocrine ablation and killed 1 hour later. The amount of isotope bound to the nucleus of the anterior pituitary gland was not statistically different between the tumor-bearing and non-tumor-bearing controls. The hypothalamus and uterus of tumor-bearing rats bound less radioactive estradiol than control tissues, but the data were not statistically different. When estradiol was administered intravenously, plasma values were significantly lower in the tumor-bearing than in control rats. This was associated with considerable incorporation of the radioactive estradiol into the tumor. When incubated in vitro with radioactive estradiol, pituitary glands from tumor-bearing and control rats bound similar amounts of isotope. These data show that under the conditions of these experiments, pituitary glands from tumor-bearing and non-tumor-bearing rats could bind comparable amounts of radioactive estradiol, and, therefore, the inhibition of prolactin synthesis in pituitary glands from tumor-bearing animals, previously described, cannot be due to a pituitary tumor hormone-induced inhibition of estrogen binding by the pituitary gland.
Regional lung ventilation distribution among individuals with chronic heart failure after an inspiratory muscle training programm: A randomized controlled clinical trial
Authors: Daniella Brandão, Shirley Campos, Jasiel Frutuoso, Larissa Carvalho, Andrea Aliverti, Cyda Reinaux, Sílvia Marinho, Wilson Oliveira, Inês Remígio, Fabiana Vieira, Armèle Dornelas de Andrade
Journal: European Respiratory Journal (2012)

Objectives: To evaluate regional lung ventilation distribution in patients suffering from chronic heart failure (CHF) after completing inspiratory muscle training (IMT) and correlate it with functional capacity and quality of life among these individuals. Methods and Results: Nineteen CHF patients were randomly assigned to two groups: Control and IMT. Before and after muscle training, subjects were submitted to assessment protocol for respiratory muscles, digital spirometry, optoelectronic plethysmography (OEP), the six-minute walk test (6MWT) and a quality of life questionnaire (MLHFQ). There was no difference in lung function following the 12-week training period in either group. However, the IMT group showed an increase in actual and predicted MIP, higher MLFHQ score and greater distance walked in the 6MWT, as well as a reduction in the Borg scale after the 6 MWT in relation to the control. For the OEP, IMT group members exhibited higher values for total chest wall volume (Vcw), abdominal rib cage volume (Vrc,a) and abdominal volume (Vab) when compared to the control. Conclusions: For patients with CHF, IMT proved efficient in improving muscle strength, functional capacity and quality of life. The present study also analyzed the distribution behavior of lung volumes for the thoracoabdominal system in this population, showing that larger abdominal rib cage and abdomen volumes may result in more effective diaphragmatic contraction.
Potential angiogenic biomarkers in patients with non small cell lung cancer: Possible implications
Authors: Soad Abdel Ghani, Nagla Elmelegy, Aliae Mohamed-Hussein, Randa Hanna
Journal: European Respiratory Journal (2012)

To date, no single agent has gained a sufficient prognostic significance for NSCLC patients. So, there is an urgent need for new innovative biomarkers in NSCLC.  The present study was designed to: 1) Evaluate the role of Nitric Oxide (NO), Sialic Acid (SA) and Glutathione S-Transferase (GST) as prognostic indicators in NSCLC.2) Correlate the above parameters levels with the clinicopathological status of the patients.  The study included 30 patients with newly diagnosed histopathologically confirmed NSCLC, as well as 10 healthy volunteers with matched age and sex as controls. Blood samples and lung tissue biopsies were taken from all subjects on admission and after chemotherapy with and without Nimesolide (Cox-2 inhibitor).  Results: Serum and tissue levels of NO, SA and GST activities were significantly higher in NSCLC patients compared to controls. These levels decreased significantly after chemotherapy (specially if Cox-2 inhibitors were added). The serum and tissue levels of the studied parameters decreased significantly in the responders compared to resistant cases.  In conclusion, NO, SA, besides GST correlated significantly with the clinicopathological status of NSCLC patients and are considered cheap sensitive prognostic biochemical indices.
Predictive capacity of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma.
Authors: S M Ansell, T M Habermann, P J Kurtin, T E Witzig, M G Chen, C Y Li, D J Inwards, J P Colgan
Journal: Journal of Clinical Oncology (1997)

The International Prognostic Factor Index has been shown to predict the outcome of patients with predominantly B-cell lymphomas classified using traditional classifications, including the Working Formulation, but its prognostic importance has not been tested in a cohort of patients with exclusively T-cell lymphomas. This study was conducted to evaluate the prognostic significance of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma (PTCL).Seventy-eight patients (48 men and 30 women) with PTCL seen at a single institution between 1985 and 1995 were included in the analysis. The morphology and immunocytochemistry of all the original biopsy specimens were reviewed by a single pathologist and classified using the Revised European-American Lymphoma (REAL) classification. The International Prognostic Factor Index, as well as clinical and biochemical parameters, were evaluated by univariate and multivariate analyses to determine their association with patient outcome.The International Prognostic Factor Index strongly predicted survival when all patients were included in the analysis (P < .001). For patients < or = 60 years, the age-adjusted International Index significantly predicted long-term survival (P = .0218). For patients older than 60 years, the age-adjusted International Index also significantly predicted survival (P = .002). Liver involvement (P = .006) and bone marrow involvement (P = .014) were also significant prognostic factors in the univariate analysis, but only the International Index remained significant in the multivariate analysis (P = .001).The International Prognostic Factor Index, which significantly predicts outcome in patients with aggressive/intermediate-grade B-cell lymphomas, has similar prognostic importance in patients with PTCL.
Modifications of Gait as Predictors of Natural Osteoarthritis Progression in STR/Ort Mice
Authors: Blandine Poulet, Roberto de Souza, Chancie B. Knights, Clive Gentry, Alan M. Wilson, Stuart Bevan, Yu‐Mei Chang, Andrew A. Pitsillides
Journal: Arthritis & Rheumatology (2014)

Objective Osteoarthritis (OA) is a common chronic disease for which disease‐modifying therapies are not currently available. Studies to seek new targets for slowing the progress of OA rely on mouse models, but these do not allow for longitudinal monitoring of disease development. This study was undertaken to determine whether gait can be used to measure disease severity in the STR/Ort mouse model of spontaneous OA and whether gait changes are related to OA joint pain. Methods Gait was monitored using a treadmill‐based video system. Correlations between OA severity and gait at 3 treadmill speeds were assessed in STR/Ort mice. Gait and pain behaviors of STR/Ort mice and control CBA mice were analyzed longitudinally, with monthly assessments. Results The best speed to identify paw area changes associated with OA severity in STR/Ort mice was found to be 17 cm · seconds −1 . Paw area was modified with age in CBA and STR/Ort mice, but this began earlier in STR/Ort mice and correlated with the onset of OA at 20 weeks of age. In addition, task noncompliance appeared at 20 weeks. Surprisingly, STR/Ort mice did not show any signs of pain with OA development, even when treated with the opioid antagonist naloxone, but did exhibit normal pain behaviors in response to complete Freund's adjuvant–induced arthritis. Conclusion The present results identify an animal model in which OA severity and OA pain can be studied in isolation from one another. The findings suggest that paw area and treadmill noncompliance may be useful tools to longitudinally monitor nonpainful OA development in STR/Ort mice. This will help in providing a noninvasive means of assessing new therapies to slow the progression of OA.
Adrenocortical Control of the Biosynthesis of Epinephrine and Proteins in the Adrenal Medulla
Authors: R.J. Wurtman, L.A. Pohorecky, B.S. Baliga
Journal: Pharmacological Reviews (1972)

The activity of phenylethanolamine-N-methyl transferase (PNMT) in the adrenal medulla declines markedly after hypophysectomy. Enzyme activity is restored if animals are treated with ACTH or very large doses of glucocorticoids, but not by replacement doses of glucocorticoids or by other pituitary or adrenal hormones. These observations indicate that basal levels of PNMT activity require that the medulla receive the very high concentrations of hydrocortisone or corticosterone that are available to it by virtue of its unique location within an envelope of adrenal cortex.

The resotration by dexamethasone treatment of the PNMT activity in medullas of hypophysectomized animals is blocked by concurrent administration of actinomycin D or puromycin. Moreover, hypophysectomy is associated with decreases in the quantity of immunochemically assayable PNMT protein in the medulla and in the rate at which PNMT is synthesized from isotopically labeled amino acid precursors. These changes are also reversed by dexamethasone. Adrenomedullary polysomes are markedly disaggregated after hypophysectomy; however, polysome patterns revert to normal if animals are treated with ACTH or dexamethasone. These observations all suggest that glucocorticoids stimulate the synthesis not only of PNMT, but also of a wide variety of medullary proteins.

The decrease in adrenal PNMT activity caused by hypophysectomy is associated with corresponding decreases in the mass of chromaffin cells and in the amounts of epinephrine stored in the adrenal medulla and secreted in response to physiological stimuli. After the induction of insulin hypoglycemia, adrenals of hypophysectomized dogs release considerably less epinephrine, and more norepinephrine, than those of control animals. Inasmuch as norepinephrine is far less potent than epinephrine in accelerating the breakdown of glycogen, the impairment in epinephrine synthesis caused by pituitary insufficiency may be related to the insulin sensitivity that often characterizes this disease.
OSU-03012, a novel celecoxib derivative, induces a unique autophagy-like cell death in human hepatocellular carcinoma cells
Authors: Ming Gao, Pei-Yen Yeh, Chih-Hung Hsu, Jen-Min Feng, Ching-Shih Chen, Min-Liang Kuo, Ann-Lii Cheng
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4662 

Hepatocellular carcinoma (HCC) is one of the most common and lethal solid tumors in the world. HCC is typically refractory to almost all cytotoxic chemotherapeutic agents. OSU-03012 is a derivative of celecoxib, a cyclooxygenase (COX)-2 inhibitor. However, its primary mechanism of action is known as 3-phosphoinositide-dependent kinase-1 (PDK-1) inhibition and by which it induces apoptosis in certain cancer cells[Zhu J et al. , Cancer Res. 64:4309-18, 2004; Hsu AL et al. , J Biol. Chem . 275:11937-403. 2000]. This study sought to investigate if OSU-03012 may be effective in the treatment of HCC. OSU-03012 inhibited cell growth of Huh7, a human HCC cell line, in a dose-dependent manner, with IC50 at 1μM, which is well below the non-toxic serum concentration (5-20μM) in mice. Surprisingly, in this Huh7 cell model, western blotting analysis demonstrated that neither pPDK1 nor pAkt was suppressed by OSU-03012. Cell cycle analysis by flow cytometry indicated that OSU-03012 (5μM, 24h) significantly increased S-phase population, while did not alter sub-G1 population, suggesting that apoptosis is not a major mechanism of cell growth suppression. Western blotting analysis showed that OSU-03012 reduced protein level of cyclin D1. Furthermore, OSU-03012-treated cells exhibited cytoplasmic vacuoles which were positively stained by acridine orange and monodansylcadaverine, a phenomenon mimicking cell autophagy. The content in the OSU-03012-induced autophagosomes and its mechanistic linkage with the occurrence of autophagy-like cell death of Huh7 cells are under investigation. Together, our preliminary results indicate that OSU-03012 might be an effective therapeutic agent for HCC, but the mechanisms of action of this drug in HCC cells need to be further clarified. (This study was supported by grant DOH94-TD-B-111-001 from Department of Health, R.O.C. to National Clinical Research Center at National Taiwan University)
Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience.
Authors: J D Hainsworth, D H Johnson, F A Greco
Journal: Journal of Clinical Oncology (1992)

We previously reported excellent responses to cisplatin-based chemotherapy in a minority of patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA) of unknown primary site. We have continued to study and to treat these patients, and now report clinical characteristics, treatment results, and prognostic factors in a large group of patients identified prospectively.Between February 1978 and December 1989, we treated 220 patients with PDC or PDA of unknown primary site. The median age was 39 years; 48% of patients had predominant tumor location in the mediastinum, retroperitoneum, or peripheral lymph nodes. Specialized pathologic studies resulted in the identification of specific tumor types in only a few cases. All patients received cisplatin-based chemotherapy; between 1978 and 1984, 116 patients received cisplatin, vinblastine, and bleomycin (PVeB) +/- doxorubicin, and 104 patients treated since January 1985 received cisplatin and etoposide +/- bleomycin.One hundred thirty-eight patients (63%) had objective responses to therapy, and 58 (26%) had complete response. Thirty-six patients (16%) are currently disease-free at a median of 61 months following therapy (range, 11 to 142 months). Actuarial 10-year survival is 16%. Favorable prognostic factors identified by Cox regression analysis include: (1) predominant tumor location in the retroperitoneum or peripheral lymph nodes, (2) tumor limited to one or two metastatic sites, (3) no history of cigarette use, and (4) younger age.Patients with PDC or PDA of unknown primary site represent another group of patients for whom potentially curative therapy is available. Patients with this syndrome should be distinguished from patients with well-differentiated adenocarcinoma of unknown primary site, and should receive a trial of cisplatin-based chemotherapy.