tbuckley/cabot-search huggingface dataset:
Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03.
Authors: W U Shipley, K A Winter, D S Kaufman, W R Lee, N M Heney, W R Tester, B J Donnelly, P M Venner, C A Perez, K J Murray, R S Doggett, L D True
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess the efficacy of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation. PATIENTS AND METHODS One hundred twenty-three eligible patients with tumor, node, metastasis system clinical stage T2 to T4aNXMO bladder cancer were randomized to receive (arm 1, n=61 ) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m2 for two courses 3 weeks apart. Patients assigned to arm 2 (n=62) did not receive MCV before concurrent cisplatin and radiation therapy. Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin. Those with less than a CR underwent cystectomy. The median follow-up of all patients who survived is 60 months. RESULTS Seventy-four percent of the patients completed the protocol with, at most, minor deviations; 67% on arm 1 and 81% on arm 2. The actuarial 5-year overall survival rate was 49%; 48% in arm 1 and 49% in arm 2. Thirty-five percent of the patients had evidence of distant metastases at 5 years; 33% in arm 1 and 39% in arm 2. The 5-year survival rate with a functioning bladder was 38%, 36% in arm 1 and 40% in arm 2. None of these differences are statistically significant. CONCLUSION Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our standard induction therapy or to increase freedom from metastatic disease. There was no impact on 5-year overall survival.
Association between ADAM33 polymorphisms and asthma control
Authors: Guergana Petrova, Hisako Matsumoto, Yoshihiro Kanemitsu, Kenji Izuhara, Yuji Tohda, Hideo Kita, Takahiko Horiguchi, Kazunobu Kuwabara, Keisuke Tomii, Kojiro Otsuka, Masaki Fujimura, Noriyuki Ohkura, Katsuyuki Tomita, Akihito Yokoyama, Hiroshi Ohnishi, Yasutaka Nakano, Tetsuya Oguma, Soichiro Hozaqa, Tadao Nagasaki, Isao Ito, Tsuyoshi Oguma, Hideki Inoue, Tomoko Tajiri, Toshiyuki Iwata, Yumi Izuhara, Junya Ono, Shoichiro Ohta, Akio Niimi, Michiaki Mishima
Journal: European Respiratory Journal (2013)

Background: A disintegrin and metalloproteinase 33 (ADAM33) has been reported to play an important role in asthma.  Objective: To evaluate the potential influence of ADAM33 single nucleotide polymorphisms (SNPs) on asthma control.  Methods: In a cohort of 224 Japanese asthmatics (mean age 62.3 years, never- or ex-smokers with 10 pack-years or less; on inhaled corticosteroids for more than 4 years), 4 ADAM33 SNPs (V4, T2, T1 and S2) were analyzed to examine the associations with asthma control test (ACT). We assessed detailed disease history, pulmonary function tests, serum biomarkers and ACT results.  Results: T2 AA/AG genotype (n=66) had lower scores of components “impaired daily activity”(p=0.002) and “shortness of breath” (p=0.033) than GG (n=158), and showed higher neutrophil counts (p=0.038). When patients were stratified into two groups according to their serum levels of periostin, a marker of Th2 inflammation, T2 AA/AG (n=28) showed significantly lower scores of component “impaired daily activity” (p=0.0008) and higher neutrophil counts (p=0.023) than GG (n=57) in high periostin group (≥ 95 ng/ml, n=85). In the same group, patients with poorly controlled asthma (ACT ≤ 19) were more frequently observed in T2 AA/GA than in GG (p=0.05). These differences were not observed in low periostin group (  T1 GG/AG (n=57) showed lower scores of component “impaired daily activity” than AA (n=167) (p=0.012). As in T2, the difference was only observed in high periostin group (p=0.003). There were no associations between ACT scores and V4 or S2.  Conclusion: Minor allele of ADAM33 T2 may be involved in poor asthma control, potentially causing neutrophilic inflammation in patients with Th2 dominant inflammation.
Phase I and pharmacologic study of high doses of the topoisomerase I inhibitor topotecan with granulocyte colony-stimulating factor in patients with solid tumors.
Authors: E K Rowinsky, L B Grochow, S E Sartorius, M K Bowling, S H Kaufmann, D Peereboom, R C Donehower
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate the feasibility of escalating doses of the topoisomerase I (topo I) inhibitor topotecan (TPT) with granulocyte colony-stimulating factor (G-CSF) in minimally pretreated adults with solid tumors and to study whether G-CSF scheduling variably affects the ability to escalate TPT doses. MATERIALS AND METHODS Thirty-six patients received 121 courses of TPT as a 30-minute infusion daily for 5 days every 3 weeks at doses that ranged from 2.0 to 4.2 mg/m2/d. G-CSF 5 microg/kg/d subcutaneously (SC) was initiated concurrently with TPT (starting on day 1). Because the concurrent administration of TPT and G-CSF resulted in severe myelosuppression at the lowest TPT dose level, an alternate posttreatment G-CSF schedule in which G-CSF dosing began after TPT (starting on day 6) was subsequently evaluated. Plasma sampling was performed to characterize the pharmacologic behavior of high-dose TPT and to determine whether G-CSF altered the pharmacokinetic profile of TPT. RESULTS Severe myelosuppression precluded the administration of TPT at the first dose, 2.0 mg/m2/d, with G-CSF on the concurrent schedule. However, dose escalation of TPT with G-CSF on a posttreatment schedule proceeded to 4.2 mg/m2/d. The dose-limiting toxicities (DLTs) were thrombocytopenia and neutropenia. One partial response was noted in a patient with colorectal carcinoma refractory to fluoropyrimidines. Pharmacokinetics were linear within the dosing range of 2.0 to 3.5 mg/m2/d, but TPT clearance was lower at the 4.2-mg/m2/d dose level. At 3.5 mg/m2/d, which is the maximum-tolerated dose (MTD) and recommended dose for subsequent-phase studies of TPT with G-CSF, the area under the concentration-versus-time curves (AUCs) for total TPT and lactone averaged 2.2- and 2.3-fold higher, respectively, than the AUCs achieved at the lowest TPT dose, 2.0 mg/m2/d. The pharmacologic behavior of high-dose TPT was not significantly altered by the scheduling of G-CSF. CONCLUSION G-CSF administered after 5 daily 30-minute infusions of TPT permits a 2.3-fold dose escalation of TPT above the MTD in solid-tumor patients, whereas concurrent therapy with G-CSF and TPT results in severe myelosuppression.
Updated Overall Survival (Os) from the Phase 3 Trial, Ca184-043: Ipilimumab (Ipi) Vs Placebo (Pbo) in Patients with Post-Docetaxel Metastatic Castration-Resistant Prostate Cancer (Mcrpc)
Authors: K. Fizazi, C.G. Drake, E.D. Kwon, A. Bossi, A.J. van den Eertwegh, H.I. Scher, T.M. Beer, M.B. McHenry, D. Liu, W.R. Gerritsen, C. Logothetis
Journal: Annals of Oncology (2014)
Costimulation of cutaneous T-cell lymphoma cells by interleukin-7 and interleukin-2: potential autocrine or paracrine effectors in the Sézary syndrome.
Authors: F M Foss, Y Koc, M A Stetler-Stevenson, D T Nguyen, M C O'Brien, R Turner, E A Sausville
Journal: Journal of Clinical Oncology (1994)

PURPOSE To examine interleukin-7 (IL7)- and interleukin-2 (IL2)-induced proliferation of Sézary lymphoma cells and to consider if an autocrine or paracrine growth-stimulatory circuit involving IL7 exists in the Sézary syndrome (SS). MATERIALS AND METHODS Fresh Sézary lymphoma cells were maintained in short-term culture in the presence of cytokines, and growth was measured by incorporation of (3H)-thymidine (TdR). Expression of IL7 and IL7 and IL2 receptors (IL7-R and IL2-R, respectively) was assessed by polymerase chain amplification of first-strand complementary DNA (RT-PCR), by affinity cross-linking of radioactive iodine-125-IL7, and by dual-color fluorescence-activated cell analysis. IL-7 production was measured by immunoassay. RESULTS Sézary lymphoma cells from seven patients showed synergistic (five of seven) or additive (two of seven) proliferation when cultured in the presence of IL2 and IL7, as compared with culture with either cytokine alone. Two patients with evidence of synergistic stimulation of [3H]-TdR incorporation showed IL7-R gene expression by RT-PCR and IL7 affinity cross-linking. Incubation of all seven patients' cells with IL7 induced coexpression to varying degrees of IL7-R and IL2-R. Sézary lymphoma cells from at least three of five patients studied expressed IL7 mRNA, and skin from three of five patients studied, as well as normal skin, expressed IL7 mRNA by RT-PCR. CONCLUSION Sézary lymphoma cells respond by proliferation to IL7 plus IL2, and in some instances produce IL7. Therapeutic maneuvers should be pursued to take advantage of this potential autocrine or paracrine growth-stimulatory mechanism.
Effect of Retinyl Acetate on the Incidence of Mammary Carcinomas and Hepatomas in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Antonio Maiorana, Pietro M. Gullino
Journal: JNCI Journal of the National Cancer Institute (1980)

Studies were designed to determine the efficacy of retinyl acetate (RA) in preventing mammary tumorigenesis in C3H-Avy female mice. Mice were fed a stock diet supplemented with RA beadlets at concentrations of 83, 41, and 21 mg/kg diet. Control animals received stock diet supplemented with placebo beadlets. The RA diet was started at conception in 1 group of animals whose mothers were fed RA from the time of mating. Two other groups of animals were placed on the RA diet at weaning or at 3 months of age. Mice were killed and necropsied 1 month after the appearance of the first mammary tumor or at 15 months of age if no tumor developed. No significant difference in incidence of mammary carcinomas was found between control and RA-fed mice. The incidence was 80--90% in all groups. The number of tumors per mouse (1.6--2.1) and the tumor latency period (10.2--11.6 mo) were not influenced by RA in the diet. Two unexpected observations were made: 1) Control mice autopsied at 12 months of age or older showed a 70% incidence of hepatomas, whereas the incidences were approximately 11, 17, and 46% in mice fed 83, 41, and 21 mg RA/kg diet, respectively. 2) Severe damage to most articulations was induced by RA, even at the dose of 21 mg/kg diet, which failed to cause any other sign of toxicity.
Histopathology of Liver Carcinomas in (C57BL/6N × C3H/HeN)F&lt;sub&gt;1&lt;/sub&gt; Mice Ingesting Chlordane&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M D Reuber, J M Ward
Journal: JNCI Journal of the National Cancer Institute (1979)

(C57BL/6N X C3H/HeN)F1 male mice that ingested 30 or 56 ppm chlordane and female mice that ingested 30 or 64 ppm chlordane in the diet had highly significant incidences of carcinomas of the liver. The carcinomas varied from well differentiated to poorly differentiated and undifferentiated and were capable of invasion and metastasis. They were more poorly differentiated in mice receiving chlordane than in controls.
Tissue and Cellular Distribution of Tritium-Labeled AET in Mice2
Authors: J. R. Maisin, A. Léonard, J. Hugon
Journal: JNCI Journal of the National Cancer Institute (1965)

We demonstrated that 2-β-aminoethylisothiourea (AET) penetrates easily and without discrimination into all tissues of mice, regardless of whether they are normal or cancerous. During the first hour after administration, AET appreciably decreased the incorporation of thymidine into DNA but, on the other hand, these substances induced mitochondrial lesions 30 minutes after injection. Also, the diminution of incorporation of3H-thymidine into the DNA was more pronounced after the simultaneous administration of AET, glutathione, and serotonin than after administration of AET alone. This mixture of compounds also offered a better chemical protection against X-radiation damage than AET alone.
Difference in the dynamic state between SP-A and SP-D in the IPF lung
Authors: Hirotaka Nishikiori, Hirofumi Chiba, Mitsuo Otsuka, Kimiyuki Ikeda, Hiroki Takahashi
Journal: European Respiratory Journal (2013)

Background: Surfactant protein (SP)-A and SP-D are useful biomarkers for the diagnosis and evaluation of the activity of interstitial lung diseases. Although the concentration of both proteins in sera from idiotathic pulmonary fibrosis (IPF) patients are increased, the degree of values and the ratio of SP-A/SP-D vary according to each patient. The dynamic states of these proteins may differ in IPF lungs.  Methods: We investigated lungs of 18 IPF patients who underwent surgical open-biopsy. We stained the lung tissues using anti-human mouse monoclonal antibodies for SP-A (PE10) and SP-D (10H11). Moreover, we performed double immunostaining with CD34 which stains capillary endothelial cells or D2-40 which stains the endothelium of lymph ducts.  Results: The type II alveolar epithelial cells were hyperplastic in the IPF lung, whose cytoplasm were positive for SP-A and SP-D. Capillary vessels had developed in close contact with alveolar surface and regenerated type II alveolar epithelial cells, while lymph ducts were distributed in the center of fibrous interstinum where both proteins were negative. SP-A was not distributed in capillary vessels where only SP-D was observed. SP-A was distributed in thick mucus inside of honeycomb-cysts and ectatic respiratory tracts, but SP-D was not.  Conclusion: The difference of dynamic states between SP-A and SP-D in the lungs of patients with IPF was suggested in this study. It was thought that the export pathway to circulation of these proteins was mainly capillary vessels which distributed close to alveolar space and producing cells. SP-D might be delivered to serum more easily, while SP-A seems to be trapped by mucus inside of honeycomb-cysts and ectatic respiratory tracts.
Identifying the Most Informative Prediction Tool for Cancer-specific Mortality After Radical Prostatectomy: Comparative Analysis of Three Commonly Used Preoperative Prediction Models
Authors: Katharina Boehm, Alessandro Larcher, Burkhard Beyer, Zhe Tian, Derya Tilki, Thomas Steuber, Pierre I. Karakiewicz, Hans Heinzer, Markus Graefen, Lars Budäus
Journal: European Urology (2015)
The current situation and the perspective of respiratory care in Japanese COPD patients revealed by Japanese White Paper on home respiratory care 2010 – COPD subgroup analysis
Authors: Jun Ueki, Michiaki Mishima, Koichiro Tatsumi, Kazuhisa Takahashi, Hideki Ishihara, Hajime Kurosawa, Keisaku Fujimoto, Mariko Koyama, Kazuko Toyama
Journal: European Respiratory Journal (2011)

To assess the current situation and the perspective of respiratory care of outpatients with chronic respiratory diseases, the nationwide survey was conducted. In the patient survey, the questionnaires were sent to 3090 patients (JFPORD) and the return rate was 27%. Of the 338 COPD patients, 73% were receiving LTOT (LTOT and HMV 24%). With regard to the pharmacological treatment, Tiotropium, LABAs, ICSs, mucolytic agents, macrolides were prescribed in 57%, 72%, 50%, 51%, and 20%, respectively. Those receiving pulmonary rehabilitation (PR) and nutritional guidance accounted for 63% and 42%, which was 60% and 28% in the 2005 White Paper, respectively. Among the LTOT/HMV group, 31% had been hospitalized more than once in the past year due to exacerbation. Concerning wishes for medical staffs, the most common reply was they wanted to be taught more about the skills for self-management, which were 78% and 83% in 2010 and 2005, respectively. The most common concrete examples of this concerned PR. The three most common demands concerning LTOT were a wish for subsidy of electricity cost of the concentrator (45%), for distribution or rental of oximeters (41%), and better explanation of the response of the LTOT/HMV providers in the time of natural disaster (35%). It is suggested that there are demands regarding the needs of patients for more information about the self-management skills and an increase in opportunity to receive PR. To achieve anxiety-free respiratory care for LTOT/HMV, the reimbursement policy for the providers has to be made, especially for handling of patients in the time of natural disaster.
Analysis of the Involvement of the von Willebrand Factor–Glycoprotein Ib Interaction in Platelet Adhesion to a Collagen-Coated Surface Under Flow Conditions
Authors: Masaaki Moroi, Stephanie M. Jung, Shosaku Nomura, Sadayoshi Sekiguchi, Antonio Ordinas, Maribel Diaz-Ricart
Journal: Blood (1997)
Natural Cytotoxic Reactivity of Rat Lymphocytes Against Syngeneic Gross Virus-Induced Lymphoma2
Authors: Myrthel E. Nunn, Julie Y. Djeu, Moshe Glaser, David H. Lavrin, Ronald B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Natural Cytotoxic Reactivity of Rat Lymphocytes Against Syngeneic Gross Virus-Induced Lymphoma Get access Myrthel E. Nunn, Myrthel E. Nunn 3Laboratory of Immunodiagnosis, NCI, National Institutes of Health (NIH), Public Health Service, U.S. Department of Health Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar Julie Y. Djeu, Julie Y. Djeu 4Litton Bionetics Inc., 5516 Nicholson Lane Kensington Md 20795. Search for other works by this author on: Oxford Academic PubMed Google Scholar Moshe Glaser, Moshe Glaser 3Laboratory of Immunodiagnosis, NCI, National Institutes of Health (NIH), Public Health Service, U.S. Department of Health Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar David H. Lavrin, David H. Lavrin 4Litton Bionetics Inc., 5516 Nicholson Lane Kensington Md 20795. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald B. Herberman Ronald B. Herberman 3Laboratory of Immunodiagnosis, NCI, National Institutes of Health (NIH), Public Health Service, U.S. Department of Health Education, and Welfare, Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 2, February 1976, Pages 393–399, https://doi.org/10.1093/jnci/56.2.393 Published: 01 February 1976 Article history Received: 25 June 1975 Accepted: 12 September 1975 Published: 01 February 1976
Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance
Authors: A. Mebazaa, H. Tolppanen, C. Mueller, J. Lassus, S. DiSomma, G. Baksyte, M. Cecconi, D. J. Choi, A. Cohen Solal, M. Christ, J. Masip, M. Arrigo, S. Nouira, D. Ojji, F. Peacock, M. Richards, N. Sato, K. Sliwa, J. Spinar, H. Thiele, M. B. Yilmaz, J. Januzzi
Journal: Intensive Care Medicine (2015)
Influence of anxiety on the quality of life of people with bronchial asthma (BA)
Authors: Natalia L. Perelman, Victor P. Kolosov
Journal: European Respiratory Journal (2012)

Background. The prevalence of anxiety in BA patients is considerably higher than in healthy people. It is little known how negative emotions can influence the quality of life (QL) of BA patients with cold airway hyperresponsiveness (CAHR) in winter.

Aim. To study the influence of anxiety on the QL of BA patients in the cold season of the year.

Methods. 111 BA patients were studied in winter. They were divided into two groups: with anxiety (68) and without it (43). To estimate QL a questionnaires SF-36 and AQLQ were used. «Hospital Anxiety and Depression Scale» was applied to find out anxiety. CAHR was estimated by the results of 3-minute isocapnic hyperventilation with cold air.

Results. In the group of patients with anxiety in comparison with the patients without it there was a decrease of QL in domains PF (52.7±3.1 and 65.0±4.4, p<0.05), VT (45.3±2.3 and 59.2±2.8, p<0.001), SF (48.3±3.0 and 64.6±3.5, p<0.001) and MH (56.6±2.3 and 71.2±2.7, p<0.001) by SF-36, and in domains «Environment» (3.4±0.2 and 4.5±0.2, p<0.001) and «General Qol» (3.3±0.1 and 3.9±0.1, p<0.01) by AQLQ. The direct correlation was found out between FEV1 and «Environment» in the group without anxiety (r=0.41, p<0.01), whereas patients with anxiety did not have it. Hence, anxiety but not lung dysfunction is a dominating factor of QL decline in the latter case. The QL of patients with CAHR and anxiety gets considerably worse. The decline of QL of these patients in all domains except «Emotion» was revealed by AQLQ. The most significant worsening was obtained in domain «Environment».

Conclusion. Anxiety in BA patients has a negative influence on QL mainly on the psychosocial status. CAHR in winter also affects physical aspects of QL.
Analysis of comorbidities and treatment patterns by GOLD 2013 criteria: Pooled data from Phase III aclidinium bromide studies
Authors: David Price, Mike Thomas, Rosa Lamarca, Esther Garcia Gil
Journal: European Respiratory Journal (2014)

Background 

Inhaled corticosteroids (ICS) are overused in patients with COPD despite recommendations since 2011 limiting their use to patients at high risk of exacerbation (GOLD Groups C and D).

Aim 

To examine COPD medication use by patients before entering Phase III aclidinium studies.

Methods 

Baseline data were pooled from the placebo and aclidinium arms of three, 6-month, placebo-controlled studies evaluating aclidinium mono- or combination therapy in patients with moderate-to-severe COPD, stratified to GOLD 2013 group using SGRQ total score (surrogate for CAT). Patients with asthma were excluded.

Results 

Of 1787 patients with stable COPD (mean±SD: age 63.3±8.4 years, 63.0% male, 54.2±13.1% predicted FEV1), 56.3% were classified as low risk (Group A+B). The proportion of patients receiving ICS therapy (alone or combination) at baseline by GOLD group was assessed (Table); 41.3% and 43.5% of patients in Groups A and B, respectively, received ICS therapy (alone or combination). Overall, 93.8% patients had co-morbidities (range 91.3–98.1%), 5.7% prior history of pneumonia, 5.8 % diagnosed osteoporosis and 11.2% diabetes.

Conclusions 

Prescribing patterns for patients with COPD did not reflect guidelines, with frequent ICS use in Groups A and B. Patients in all groups had co-morbidities potentially affected by ICS use; these need to be considered before prescribing ICSs to patients with COPD.

![Figure][1]  [1]: pending:yes
Research as part of routine care
Authors: J G Williams
Journal: Journal of the Royal Society of Medicine (2001)

The Clinical Standards Advisory Group report on urgent and emergency admissions to hospital identified several important issues regarding emergency care. This paper examines what we know about the costs of a quality emergency service. Estimating the cost of a quality emergency service is not yet possible, but ongoing and future research should be capable of highlighting the costs of important service improvements. It must, however, be recognized that such work by itself will not automatically lead to increased funding within emergency care. Further consideration must be given to the funding arrangements for emergency care if long-term improvements are to be secured.