tbuckley/cabot-search huggingface dataset:
Updated results of a multicenter phase II trial of neoadjuvant docetaxel, carboplatin and capecitabine for inflammatory and locally advanced breast cancer (LABC)
Authors: S. X. Franco, A. Perez, E. Tan-Chiu, F. Gokce, C. Frankel, L. S. Schwartzberg, E. Krill, J. Jakub, N. Abramson, C. Vogel
Journal: Journal of Clinical Oncology (2006)

10685 Background: Neoadjuvant chemotherapy for the treatment of LABC has become the standard of care but the best combination is not established. The combination of docetaxel and capecitabine demonstrates synergism in patients(pts) with metastatic breast cancer (MBC). Recent studies support the value of platinum salts in LABC and MBC. Methods: pts with stage IIA-IIIC or inflammatory BC, EGOG PS 0–1, are eligible.We are evaluating the combination of weekly docetaxel 30mg/m 2 , carboplatin AUC2 on D1, 8,15 of a 4-week cycle plus capecitabine 625 mg/m 2 BID given on days 5–18 (based on the upregulation of thymidine phosphorylase) for 4 cycles prior to surgery. The primary objective of this phase II trial is pCR rate in breast. Results: 39 of 48 pts have been enrolled from 7 centers. Median age 46 (range 26–75), stage II 41%, stage III 59%. Median baseline tumor is 5.4cm (range 2.1–15); 1pt inflammatory BC; 10 pts N2 disease (36%); 12 tumors were ER+, 20 ER-, and 5 Her-2+. To date, 2,377 doses (including daily capecitabine doses) were administered out of a total of 2,560 (93% of intended doses) with only 10 dose delays and 8 dose reductions. 37 pts are evaluable for toxicities. No grade IV toxicities were seen, grade III neutropenia was seen in 3/37(8%) and grade III fatigue in 1/37(3%). There were no episodes of neutropenic fever.The most common grade I/II toxicities were nausea in 57%, diarrhea 38%, fatigue 43%, epiphora 24%, mucositis 24% and hand-foot syndrome 3%. No death related treatments have been reported. 32 pts have completed definitive surgery. Objective clinical response is 94% with 53% cCR. 5 patients had pCRs in breast(16%) and 5 pCR in breast and axilla(16%). 9 pts (28%) have microscopic residual disease in the breast (&lt;3mm). 14 pts had complete axillary clearance (44%). Conclusions: The preoperative combination of docetaxel, carboplatin and capecitabine is feasible with very good response rate and a very acceptable toxicity profile. Accrual is ongoing. No significant financial relationships to disclose.
Abstract P047: The Role of the Healthy Heart Score in the Primordial Prevention of CVD Among Women
Authors: Mercedes Sotos-Prieto, Josiemer Mattei, Frank B Hu, Andrea K Chomistek, Eric B Rimm, Walter C Willett, A H Eliassen, Stephanie E Chiuve
Journal: Circulation (2015)

Background:  Currently, clinical practice focuses on primary prevention of CVD by treating individuals at high risk of CVD based on the presence of clinical risk factors, rather than preventing the development of clinical risk factors through maintenance or adoption of a healthy lifestyle. We recently derived and validated the Healthy Heart Score, which estimates the 20-year risk of CVD based on modifiable lifestyle factors. The Healthy Heart Score in mid-adulthood effectively predicted CVD events; however whether this risk score can play an important role in the prevention of clinical CVD risk factor development, or primordial prevention of CVD, is not known.   Methods:  We conducted a prospective analysis among 69,264 women, in the Nurses’ Health Study II, aged 26-45 years at study baseline in 1991 and free of CVD, diabetes, hypertension and hypercholesterolemia. Diet and lifestyle factors were first assessed in 1991 and were updated by questionnaires every 2-4 years. The Healthy Heart Score was calculated at study baseline as the 20-year risk of CVD, based on a prediction model that includes age, smoking, BMI, hours of moderate to vigorous exercise, alcohol intake and a composite diet score (fruit & vegetables, sugar-sweetened beverages, red/processed meats, cereal fiber, nuts). Self-reported diabetes was validated by supplementary questionnaires. Physician-diagnosed hypertension and hypercholesterolemia were self-reported from biennial questionnaires. Cox proportional hazards models were used to calculate hazard ratio (HR) for developing clinical CVD risk factors (diabetes, hypertension, hypercholesterolemia), adjusting for parental history of MI, aspirin use, menopausal status, postmenopausal hormone use, parity, and oral contraceptive use.   Results:  Through 2011 (996,553 person-years of follow-up), we documented 2,745 diabetes, 16,605 hypertension and 20,926 hypercholesterolemia cases. The median 20 year risk of CVD based on the Healthy Heart Score was 0.8% at baseline (mean age 36). Compared to women in the lowest quintile of the Healthy Heart Score (median CVD risk: = 0.35%), women in the highest quintile (median CVD risk: 2.5%) had a HR (95%CI) of 5.1 (4.2, 6.2) for diabetes; 2.1 (1.9, 2.2) for hypertension and 1.4 (1.3, 1.5) for high cholesterol. The HR (95%CI) for developing ≥1 risk factor across quintiles was Q1: 1.0 (ref); Q2: 1.22 (1.16, 1.28); Q3: 1.34 (1.27, 1.40); Q4:1.48 (1.41, 1.56); Q5: 1.51 (1.43, 1.58); P-trend   Conclusion:  The Healthy Heart Score in early adulthood was strongly associated with the development of CVD risk factors among middle-aged women. Therefore, the Healthy Heart Score may be a useful tool in the clinic or community-based setting to evaluate the primordial prevention of CVD and help maintain ideal cardiovascular health among women.
Rapidly alternating chemotherapy and hyperfractionated radiotherapy in the management of locally advanced head and neck carcinoma: four-year results of a phase I/II study.
Authors: S Leyvraz, P Pasche, J Bauer, S Bernasconi, P Monnier
Journal: Journal of Clinical Oncology (1994)

PURPOSE Treatment of locally advanced head and neck carcinoma by surgery and/or radiotherapy is associated with a high recurrence rate, poor survival, and, often, limitation in speech and swallowing functions. Because prolonged time of treatment might be detrimental for tumor control, we designed a study to develop a schedule of alternating radiotherapy and chemotherapy that should be administered over the shortest period of time and with the highest dose of radiotherapy as possible. PATIENTS AND METHODS Following four successive steps of schedule modifications, regimens alternating split hyperfractionated radiotherapy (2.0 Gy/d times three over 30 to 40 days, to a total of 48 Gy to 60 Gy) and chemotherapy (cisplatin 80 to 100 mg/m2 and fluorouracil 1,000 mg/m2 by continuous infusion for 3 to 4 days, +/- vindesine 8 mg/m2 for two cycles) were administered in 91 patients with advanced squamous cell carcinoma of the head and neck. Adenectomy was performed for residual nodes and major surgery for progression only. RESULTS The overall response rate was 95.6% (95% confidence interval [CI], 89.1 to 98.8), with 69.2% complete and 26.4% partial responses. Among partial responders, two patients were converted into complete responders by resection of a residual node. With a median follow-up duration of 45 months, distant mestastases occurred in 18% and a second primary tumor in 7.7% of patients. The median overall survival (OS) and progression-free survival (PFS) durations were 24 months and 17 months, respectively. At 4 years, the survival rate was 40%. All of the locoregional recurrences occurred within the first 15 months, in 14% and 73% of the complete and partial responders, respectively. Mucositis was the dose-limiting toxicity, with a World Health Organization (WHO) grade III and IV rate of 81% at a 60-Gy dose of radiotherapy, compared with 65% at 48 Gy or 54 Gy, which precluded further dose escalation. Leukopenia was severe in the first two steps of treatment, with WHO grade IV toxicity occurring in 41% of patients; however, this decreased to 10% when vindesine was deleted from the chemotherapy regimen in the last two steps. Late toxicity in 29% of patients was not different from that expected with radiotherapy alone. Among patients with resectable tumors, a 64% rate of organ preservation was obtained. CONCLUSION We demonstrated that a full dose of hyperfractionated radiotherapy alternated with chemotherapy over 40 days could produce high antitumor activity. Mucositis was the dose-limiting toxicity, but this resolved completely within a median period of 6 weeks.
Studying General Practice in the Inner City — A Model for Linking Available Sources of Data: Preliminary Communication
Authors: Peter Fitton, Paul Freeling
Journal: Journal of the Royal Society of Medicine (1982)

The effect of implementing proposals intended to improve general practice primary care in inner London is not known. To test it requires a model of how general practice works and methods of measuring appropriate variables. The methods must be sufficiently simple to allow measurement prior to, as well as during, change. This paper presents such a model, describes methods used to measure some of those variables, and illustrates the results.
Gender differences of predictors of health status in patients with COPD
Authors: Mihaela Coliba, Alexandru Corlateanu, Victor Botnaru
Journal: European Respiratory Journal (2011)

Background:  In recent years there has been an increase in the incidence, prevalence and mortality of COPD in women. The influence of gender on the health status of COPD patients is studied rather superficially.   The aim  of the study was to to evaluate the health status of COPD patients and to identify the main predictors of quality of life in these patients according to the gender.   Methods:  80 consecutive COPD patients were enrolled into the study. Spirometric data were analyzed (FEV1, FVC, FEV1/FVC) and BODE index (BMI, FEV1, MRC, 6 MWD). Health-related quality of life was assessed by the Clinical COPD Questionnaire (CCQ) and the St. George Respiratory Questionnaire (SGRQ).   Results:  The cohort consisted of 40 women with mean age 65±8.3 years and 40 men with mean age 64±8 years. Patients in both groups had the similar severity of COPD by GOLD/ATS/ERS: FEV1,% was 46.27±15% versus 44.9±9.5% (p= 0.62). Patients in both groups had similar scores of all domains of the SGRQ: total 62.23 vs 65.01, p= 0.29; symptoms 76.46 vs 80.63, p=0.29; activity 57.49 vs 59.35, p=0.58; impact 60.49 vs 63.35, p=0.29. There were no significant differences in CCQ total score 2.96 vs 2.8, p=0.38. The forward stepwise regression analysis shows that the BODE index, severity of obstruction and comorbidities are the important predictors of health related quality of life in men, which explain 55% of the total score of SGRQ (p   Conclusion:  BODE index, degree of obstruction and comorbidities were found to be the major determinats of quality of life in men, meanwhile age, exercise capacity and level of arterial oxygenation in women.
Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor infusion makes high-dose etoposide a safe outpatient regimen that is effective in lymphoma and myeloma patients.
Authors: A M Gianni, M Bregni, S Siena, M Magni, M Di Nicola, F Lombardi, C Tarella, A Pileri, G Bonadonna
Journal: Journal of Clinical Oncology (1992)

PURPOSE This study assessed the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or recombinant human granulocyte colony-stimulating factor (rhG-CSF) in ameliorating the extent and duration of hematologic toxicity after high-dose etoposide cancer therapy. PATIENTS AND METHODS Thirty-two non-Hodgkin's lymphoma and myeloma patients were treated with 2 to 2.4 g/m2 etoposide infused intravenously (IV) during a 10- to 12-hour period, followed 72 hours later by subcutaneous administration of rhGM-CSF or rhG-CSF. Hematologic toxicity was compared with that observed in 29 patients who were treated with high-dose etoposide without growth factors. RESULTS The median duration of grade 4 neutropenia in growth factor-treated patients was 3 days, and granulocyte counts never decreased to less than 100/microL in approximately half of the patients. The corresponding figures in the control patients were 8 and 3 days, respectively (P &lt; .0001). No effect was observed in platelet and RBC recovery. Growth factor-treated patients became eligible to receive additional myelotoxic chemotherapy a median of 5 days earlier than controls. Nonhematologic toxicity was minimal. Grade 1 mucositis was observed in two of 61 patients (3%). Antitumor activity assessed within 1 month after etoposide administration was documented in 58% of 38 assessable patients. Finally, high-dose etoposide expanded and mobilized the pool of peripheral-blood hematopoietic progenitors. CONCLUSION The use of rhGM-CSF or rhG-CSF makes high-dose etoposide a safe outpatient regimen and should encourage the inclusion of this highly effective and well-tolerated drug in novel treatment strategies that use high-dose therapy early in the clinical course of chemosensitive tumors.
Ontario suspends unvaccinated children from school and proposes mandatory classes for parents
Authors: Owen Dyer
Journal: BMJ (2015)

A new law proposed by Ontario’s health minister would require parents seeking their children’s exemption from being vaccinated on religious or philosophical grounds to first attend an education session on the risks of avoiding vaccination.

The province, Canada’s largest, has struggled for years with low vaccine coverage among schoolchildren, particularly in and around Toronto, where in many schools less than 70% of students are up to date with their recommended vaccination schedule.

In recent years public health authorities have instructed schools across the province to suspend children who are seriously behind in their vaccination schedule or cannot provide evidence of being up to date. This week Ottawa …
Liposomes loaded with P. falciparum merozoite-derived proteins are highly immunogenic and produce invasion-inhibiting and anti-toxin antibodies
Authors: Wesley L. Fotoran, Rachele M. Santangelo, Márcia M. Medeiros, Marcelle Colhone, Pietro Ciancaglini, Renato Barboza, Claudio Romero Farias Marinho, Rodrigo Guerino Stábeli, Gerhard Wunderlich
Journal: Journal of Controlled Release (2015)
Evaluation of the association between anticarbamylated protein antibodies and the longitudinal course of functional ability in rheumatoid arthritis
Authors: S Ajeganova, B Svensson, T W J Huizinga, A H M van der Helm-van Mil, H W van Steenbergen
Journal: Annals of the Rheumatic Diseases (2015)

Clinically relevant joint destruction has now become infrequent in patients with newly diagnosed rheumatoid arthritis (RA), while other disease outcomes such as functional ability and disease persistence have become more important. Recently, novel auto-antibody reactivities have been identified in RA, with the ultimate aim to better characterise patients with RA. Anticarbamylated protein (anti-CarP) antibodies were recently identified and associated with more severe radiographic progression,1 but the association with other outcomes was unexplored. With great interest we read the study by Humphreys et al ,2 reporting more severe functional disability in anti-CarP positive patients with inflammatory polyarthritis. According to the reported unadjusted β-coefficient (95% CI), patients with anti-CarP antibodies had 0.21 (0.14 to 0.29) higher scores on the Health Assessment Questionnaire (HAQ) during a median follow-up duration of 8 years. This association was statistically independent of the presence of anticitrullinated peptide antibodies (ACPA) and rheumatoid factor (RF). In general replication …
Efficient isolation of monocytes from PBMCs utilizing a newly developed material
Authors: Xue Zhang, Takayuki Miyamoto, Yoshiko Miura
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Recent years immunotherapy has been used to treat various diseases especially cancer. The dendritic cell therapy has been one of the most widely practiced therapies in clinics and usually monocytes are isolated as the source of dendritic cells. However, although dendritic cell
Rho-kinase inhibitor ameliorates bleomycin-induced chronic lung injury in neonatal rats
Authors: Alvin H. Lee, Crystal Kantores, Julijana Ivanovska, Charlotte Sewing, Robert P. Jankov
Journal: European Respiratory Journal (2011)

Bleomycin (BLEO) induces a chronic neonatal lung injury (CNLI) in rats that is characterized by inflammation, arrest of lung development and pulmonary hypertension (PHT), similar to severe bronchopulmonary dysplasia. Increased Rho-kinase (ROCK) signaling contributes to experimental inflammatory lung injury in adult animals but its role during early life remains unknown.

Methods: Rat pups received BLEO (1 mg/kg/d i.p.) or saline vehicle from postnatal days 1-14 ± Y27632 (a ROCK inhibitor; 10 mg/kg/d i.p.). Inflammation was assessed by tissue counts of immunoreactive macrophages (CD68) and neutrophils (MPO). Chronic PHT was assessed by right ventricle/left ventricle+septum weight ratio and% medial wall thickness of pulmonary resistance arteries. Markers of lung growth, injury and alveolarization included weight, tissue fraction, mean linear intercept and secondary crest counts.

Results: Lungs of BLEO-exposed pups had up-regulated ROCK activity, as evidenced by increased phosphorylation of ROCK targets, MYPT-1 and LIMK1, which was completely inhibited by Y27632. Treatment with Y27632 completely prevented neutrophil influx to the BLEO-exposed lung while having no effect on increased macrophages. Y27632 completely prevented BLEO-induced PHT and partially improved septal thinning, but did not affect inhibited lung growth or alveolarization. Complete abrogation of BLEO-mediated neutrophil influx by treatment with SB265610 (a CXCR2 antagonist; 4 mg/kg/d) had no effect on parenchymal or vascular injury.

Conclusions: ROCK inhibition prevented chronic PHT and improved parenchymal injury (septal thinning) in BLEO-mediated CNLI, independent of changes in inflammatory cells. Funded by the CIHR.
US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary
Authors: R Andres Floto, Kenneth N Olivier, Lisa Saiman, Charles L Daley, Jean-Louis Herrmann, Jerry A Nick, Peadar G Noone, Diana Bilton, Paul Corris, Ronald L Gibson, Sarah E Hempstead, Karsten Koetz, Kathryn A Sabadosa, Isabelle Sermet-Gaudelus, Alan R Smyth, Jakko van Ingen, Richard J Wallace, Kevin L Winthrop, Bruce C Marshall, Charles S Haworth
Journal: Thorax (2015)

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with pre-existing inflammatory lung disease, such as cystic fibrosis (CF). Pulmonary disease (PD) caused by NTM has emerged as a major threat to the health of individuals with CF, but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened a panel of 19 experts to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM-PD in individuals with CF. PICO (population, intervention, comparison, outcome) methodology and systematic literature reviews were employed to inform draft recommendations, which were then modified to achieve consensus and subsequently circulated for public consultation within the USA and European CF communities. We have thus generated a series of pragmatic, evidence-based recommendations as an initial step in optimising management for this challenging condition.
High-purity magnesium interference screws promote fibrocartilaginous entheses regeneration in the anterior cruciate ligament reconstruction rabbit model via accumulation of BMP-2 and VEGF
Authors: Pengfei Cheng, Pei Han, Changli Zhao, Shaoxiang Zhang, Hongliu Wu, Jiahua Ni, Peng Hou, Yuanzhuang Zhang, Jingyi Liu, Haidong Xu, Shen Liu, Xiaonong Zhang, Yufeng Zheng, Yimin Chai
Journal: Biomaterials (2015)
Repeated In Vitro Fertilization Cycles for Infertility
Authors: Evan R. Myers
Journal: JAMA (2015)

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Cold agglutinin titers in psychiatric patients
Authors: B Spivak, M Radwan, D Elimelech, A Molcho, G Avidan, R Ohring, S Tyano
Journal: American Journal of Psychiatry (1988)

Cold agglutinin titers were obtained from the serum of 41 psychiatric patients. The 21 chronic schizophrenic patients tended to have positive cold agglutinin titers; the authors suggest that this immunological finding may be associated with long-term neuroleptic treatment.
A "Combination Method" of Family Planning
Authors: M O Kepler
Journal: New England Journal of Medicine (1971)

It is recommended by the physician writer that mechanical contraception be combined with legal abortion for a combination method that has 100% efficacy and a 7-fold lower maternal mortality than any single method of family planning except  sterilization or abstinence.  This method would have a maternal mortality rate of 3 per million compared with a rate of 21 per million annually for oral contraceptive users.  In looking at other maternal mortality rates it appears that a saving of human lives would be derived from use of the combination methods that include abortion as an integral component of family planning.  The psychological social and behavioral impact of a decision to abort upon the mental and emotional health of either the woman or her family has not been studied.  Difficulties of a legal economic cultural moral religious and administrative nature are likewise to be expected if combination methods that include abortion are employed on a widespread basis before prospective scientific evaluation.