tbuckley/cabot-search huggingface dataset:
Phase II study of pazopanib with weekly paclitaxel in refractory urothelial cancer.
Authors: Sandy Srinivas, Sujata Narayanan, Lauren Christine Harshman, Russell Kent Pachynski, Anthony P. Lam, Alice C. Fan, Shermeen Poushnejad, Denise Haas, Ulka N. Vaishampayan
Journal: Journal of Clinical Oncology (2015)

294 Background: Currently, there are no standard treatments for relapsed or refractory urothelial carcinoma (UC). Discouraging results have been observed in trials evaluating established chemotherapeutics as single agents or in combination regimens. Paclitaxel has moderate activity when used alone and in combination in UC. Pazopanib is active in other solid tumors secondary to its potent anti-angiogenic effects. We report the results of a multi-center phase II study evaluating the combination of paclitaxel with pazopanib in refractory UC. Methods: Eligible patients (pts) had histologically confirmed UC, with disease that progressed on upto 2 chemotherapeutic regimens. Pazopanib (800 mg) was administered daily, with weekly paclitaxel (80mg/m2) for 3 weeks in a 28 day cycle. Treatment was continued until disease progression or unacceptable toxicity. The primary endpoint of the study was response-rate (RR) based on RECISTv 1.1 criteria. Secondary endpoints included safety, and progression free-survival (PFS). Results: From April 2010 to September 2014, 32 patients were enrolled. Median age was 67 years (29-89) and median ECOG performance status was 1 (0-2). 17 pts (54%) had UC of the upper urinary tract disease and 15(47%) had primary bladder tumors. All pts had multiple metastatic sites, including 9 (28%) with liver metastases. Median number of prior cytotoxic regimens was 2, and 50% were considered cisplatin responsive. Objective responses were observed in 58% with 3 (12%) complete responses (CR), and 12 pts (46%) with partial responses (PR). Another 9 (35%) acheived stable disease (SD). High grade toxicities included grade 3 hypertension (n=2), grade 3 fatigue (n=4), grade 3 thrombosis (n=2) and grade 4 neutropenia (n=2). Nearly half of the patients( n= 14 ) required growth factor support. Conclusions: Our phase II study combining paclitaxel and pazopanib demonstratedsignificant anti-tumor activity in relapsed/refractory UC. This combination is safe, effective and is worthy of evaluation in randomized phase 3 study. Clinical trial information: NCT01108055.
Reevaluation of the Effect of Mouse Mammary Tumor Virus Infection on the BALB/c Mouse Hyperplastic Outgrowth&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Rhoda L. Ashley, Robert D. Cardiff, Thomas G. Fanning
Journal: JNCI Journal of the National Cancer Institute (1980)

The BALB/c (C-) mouse hyperplastic outgrowth line (D1) was used to study murine mammary tumor virus (MuMTV) expression in both D1 and tumors derived from D1. D1 was transplanted into virus-infected BALB/cfC3H (C+) and virus-uninfected C- animals. In duplicate studies, tumor incidence was the same in both groups. However, the tumor latency period was longer for D1 transplanted into C+ mice (D1/C+) than for D1 transplanted into C- mice (D1/C-). MuMTV was detected in 85% of D1/C+ outgrowths and in 29% of D1/C+ tumors but was never detected in D1/C- outgrowths or tumors. D1/C- outgrowth and tumors and most of the D1/C+ tissues expressed little or no MuMTV RNA. Some D1/C+ tumors expressed substantial levels of MuMTV RNA. These same tumors also had MuMTV antigen and contained the exogenously acquired C3H-MuMTV provirus in the cellular DNA as shown by DNA fragment patterns following cleavage with Pst I and Eco RI endonucleases. D1/C+ tumors containing no viral RNA were also antigen-negative and lacked the acquired C3H provirus. These studies indicate that D1 has substantially changed in its incidence and in its response to MuMTV. MuMTV infection was not tumorigenic in the traditional sense, a finding that has led to a reevaluation of our current models of virus-host relationships and the biology of precancerous conditions.
Combination therapy (beta-lactam+macrolide) vs fluoroquinolone monotherapy for the treatment of CAP
Authors: Charalampos Triantafyllidis, Vasilios Kapordelis, Elissavet-Christina Philippidou, George Papaetis, Maria Apostolidou, Ioannis Nikolopoulos, Dora Orfanidou, Angelos Pefanis
Journal: European Respiratory Journal (2012)

BACKGROUND: According to the 2007 IDSA/ATS guidelines for the treatment of CAP monotherapy with fluoroquinolones is the first choice and combination therapy remains an alternative treatment option. Combination therapy was the first recommended treatment option by the 2003 IDSA update of practice guidelines for the treatment of CAP.

AIM OF STUDY: The aim of this study was to assess whether any of the two proposed alternative treatment options for CAP is statistically superior and related with advanced clinical course.

MATERIAL AND METHODS: A prospective observational study which incorporated 300 immunocompetent adults, who referred to the ER of Sotiria General Hospital for Thoracic Diseases and after diagnosed with CAP, were all hospitalized.

RESULTS: 250 patients (83.33%) received combination therapy and 50 patients (16.67%) received monotherapy with fluoroquinolone. 235 (94%) out of the 250 patients who received combination therapy had a favourable clinical course (survived) and 15 (6%) had an unfavourable clinical course (died). 42 (85%) out of the 50 pts who received monotherapy with fluoroquinollone survived and 8 (15%) of them died. The mortality rate of the second group was significantly higher than the mortality rate of the first group (15% vs 6% respectively, p=0.033).

CONCLUSION: The mortality rate of hospitalized patients with CAP receiving monotherapy with fluoroquinolones was significantly higher compared to patients receiving combination therapy. There are a few other studies supporting these results and one possible explanation could be the immunomodulating activity of macrolides, which is verified but still a field of detailed, extended and persistent investigation.
HELPing people with very severe COPD: Feasibility study of a novel holistic intervention
Authors: Susan Buckingham, Marilyn Kendall, Susie Ferguson, Aziz Sheikh, Scott A. Murrray, William MacNee, Patrick White, Allison Worth, Kirsty Boyd, Hilary Pinnock
Journal: European Respiratory Journal (2013)

Background  Identifying a point of transition to palliative care in COPD is problematic. We thus propose linking proactive holistic assessment of supportive care needs with milestones throughout a patient’s journey.   Aim  To pilot HELP-COPD: holistic intervention delivered at home after hospital admission with COPD.   Method  We recruited 30 inpatients at two NHS Lothian hospitals. After discharge a respiratory nurse assessed social/psychological/spiritual/physical needs, provided advice/information and made further clinical/social care referrals. A summary was given to the patient and their general practitioner. Follow-up included three phone calls over six months. A researcher interviewed participating patients, lay-carers and health professionals to assess feasibility and acceptability.   Results  Patients were generally positive about the assessment, openly discussing concerns and coping strategies in all domains and appreciating the opportunity for conversation as opposed to completing forms. Professionals considered that the intervention was feasible but identified fewer unmet needs than expected, and some patients were reluctant to access proffered services/information. Participants highlighted overlap with discharge planning and case management provided by community teams.   Conclusion  The HELP COPD holistic assessment was feasible and generally welcomed by patients. Fewer actions were identified than anticipated; perhaps due to a combination of inappropriate timing, reluctance to accept social services, long-term adaptation reducing recognition of need, duplication by existing services.   Funding  Dunhill Medical Trust.
Action and Interaction of Hormones and 3-Methylcholanthrene on the Ventral Prostate Gland of the Rat &lt;italic&gt;In Vitro&lt;/italic&gt;. II. Hydrocortisone and Methylcholanthrene
Authors: Ilse Lasnitzki
Journal: JNCI Journal of the National Cancer Institute (1965)

The action and interaction of hydrocortisone and 3-methyl-cholanthrene (MCA) were studied in organ cultures of the ventral prostate gland of the rat, grown in natural and semidefined medium. Hydrocortisone alone attenuated the regression of the alveolar epithelium that occurs in medium without added hormones. In natural medium MCA alone stimulated mitosis and induced rapid and extensive hyperplasia of the alveolar epithelium. After transfer to control medium this process was at first halted but then resumed. In the semidefined medium the hyperplasia was less extensive. Hydrocortisone, if combined with MCA, almost completely suppressed the epithelial hyperplasia in both media. If administered to explants pretreated with the carcinogen, the hormone partially inhibited the hyperplasia. Possible mechanisms for the modification of the carcinogen's effect by hydrocortisone are discussed.
Phase I study of docetaxel with concomitant thoracic radiation therapy.
Authors: A M Mauer, G A Masters, D J Haraf, P C Hoffman, S M Watson, H M Golomb, E E Vokes
Journal: Journal of Clinical Oncology (1998)

PURPOSE The taxanes have demonstrated activity as radiation sensitizers in preclinical studies. This study was designed to determine the maximum-tolerated dose (MTD), optimal schedule, and toxicities of docetaxel in combination with concomitant standard chest radiotherapy. PATIENTS AND METHODS Twenty-nine patients with advanced non-small-cell lung or esophageal cancer enrolled in this phase I study to evaluate escalating docetaxel doses at three schedules. Docetaxel was administered as two 21-day cycles at doses of 40, 60, and 75 mg/m2 per cycle. Docetaxel administration schedules were as follows: schedule A, once every 3 weeks; schedule B, 2 of 3 weeks; or schedule C, weekly. Six weeks of concomitant standard chest radiotherapy in 1.8- to 2.0-Gy daily fractions was delivered to 60 Gy total. RESULTS Dose-limiting esophagitis and neutropenia were encountered with schedules A and B at docetaxel doses of 60 mg/m2 per cycle. The docetaxel MTD for schedules A and B was 40 mg/m2 per cycle. Dose-limiting esophagitis was also observed with schedule C; however, there was no neutropenia. For schedule C, we identified the MTD as 60 mg/m2 per cycle (20 mg/m2/wk). Other toxicities encountered included thrombocytopenia, hypersensitivity reaction, and pulmonary infiltrates (fatal in two patients). Late toxicity of esophageal stricture occurred in five patients. CONCLUSION Esophagitis and neutropenia are the dose-limiting toxicities of docetaxel administered with concomitant chest radiotherapy. Weekly administration of docetaxel allows for the highest total docetaxel dose during chest radiotherapy. We identified the recommended phase II docetaxel dose as 20 mg/m2 administered weekly with concomitant chest radiotherapy for 6 weeks.
Factors Influencing the Quantitative Estimation of the &lt;italic&gt;In Vivo&lt;/italic&gt; Survival of Cells From Solid Tumors&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: R. F. Kallman, G. Silini, L. M. van Putten
Journal: JNCI Journal of the National Cancer Institute (1967)
Fibroblast growth factor 23 (FGF23) and hypophosphatemia in patients with COPD
Authors: Mohamed Elsammak, Adel Attia, Moosa Suleman
Journal: European Respiratory Journal (2011)

Introduction: Previous studies highlighted the importance of phosphate depletion in COPD patients and the association between correction of hypophosphatemia and improvement in respiratory muscle function. Fibroblast Growth Factor 23 (FGF23) is a recently discovered circulating protein that plays a crucial role in renal phosphate reabsorption and body phosphate regulation. FGF23 has been investigated in several diseases but there is currently no published data about FGF23 in COPD.

Aims and objectives: The aim of this study was to evaluate whether FGF23 levels correlate with serum phosphate levels and disease severity in COPD patients.

Methods: 70 COPD patients aged 63.0±4.6 years and 34 age and sex matched randomly selected controls were studied. Criteria for diagnosing COPD and assessing severity were according to GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines. Serum samples were analyzed for routine tests including calcium, phosphate, renal/lytes, and FGF23 levels were measured by a commercially available Eliza kit.

Results: There were no differences in serum calcium and Vitamin D levels in COPD patients and controls (P > 0.05). COPD patients had significantly lower serum phosphate levels compared to controls (P< 0.01). Plasma FGF23 was significantly higher in patients compared to controls: 280 (51-968) versus 140 (21-200) RU/ml (P < 0.001). As expected plasma FGF23 levels correlated negatively with serum phosphate (r = -0.799 & P< 0.001). Furthermore plasma FGF23 correlated negatively with FEV1 (r = -0.352 & P = 0.003)

Conclusion: This study illustrates a significant increase in plasma FGF23 levels that may contribute to low phosphate levels and disease severity in COPD patients.
Hard diagnosis of intrathoracic sarcoidosis in male patients
Authors: Mourad Zarrouk, Nawel Ben Salem, Nawel Chaouch, Manel Loukil, Sana Cheikh Rouhou, Hajer Racil, Kamel Marnich, Abdellatif Chabbou
Journal: European Respiratory Journal (2011)

Typical presentations of sarcoidosis are easily diagnosed. Atypical forms have unusual presentation making diagnosis hard.  We studied four cases with unusual presentations of thoracic sarcoidosis.  Over a period of 7 years we diagnosed intrathoracic sarcoidosis in four male patients. Clinical and radiological characteristics were reviewed.  The mean age was 40 years. All cases had fever, sweat and respiratory symptoms including dyspnea, cough and chest pain. Chest X ray and CT scan showed bilateral hilar lymphoma in all cases, with multiple large lung nodules in one case, cavitation in one case and large alveolar opacity in another case. Tissue biopsy showed in all cases non-caseating granuloma, by bronchial lung biopsy in one case, peripheral lymph node in one case, skin biopsy in one case and by mediastinoscopy in another case.  Diagnosis of tuberculosis was initially evoqued in two cases but the outcome was non favorable under antituberculous therapy and diagnosis was revised. In one case, diagnosis of BOOP was suspected but skin biopsy confirmed sarcoidosis. In another case, multiple large disseminated lung nodules led for a rather neoplasic diagnosis.  Diagnosis of unusual presentations of sarcoidosis requires the association of clinical features, evidence of non caseating granuloma in histologica and exclusion of infection, malignancy and other granulomatous diseases.
Improving adult asthma care in England: Emerging learning from a programme of national improvement projects
Authors: Hannah Wall, Phil Duncan, Alex Porter
Journal: European Respiratory Journal (2012)

Introduction : Asthma is a long-term respiratory condition affecting up to 5.9% of the England population. There have been between 1000 and 1200 deaths a year since 2000 with almost 40% of these under 75 years old. Asthma is responsible for large numbers of emergency attendances to Emergency Departments and emergency admissions.   Aims : To use service improvement approaches to define the patient pathway in order to improve the patients experience and outcomes of care – and reduce overall variation.   Method : Seven improvement projects from primary and secondary care used improvement methodologies to analyse the existing patient pathway, implement service redesign and assess the impact for patients with asthma in relation to: diagnosis and medicines optimisation, chronic disease management and acute care. Primary care data was used to identify cohorts of patients eligible for diagnosis and review and secondary data was used to demonstrate areas of duplication and gaps in service provision.   Results : Implementation of principles such as: primary care register reviews, self-management support, medicines optimisation, standardised care in acute settings and primary care follow-up on discharge have demonstrated cost savings and increased productivity in a number of improvement projects. Project data on reduction in admissions and Emergency Department attendances demonstrates improved outcomes. Patient feedback highlights a positive experience of redesigned services.   Conclusion : There is variation in the delivery and quality of asthma services in England. Systematic improvement approaches reduces variation and increase productivity as well as delivering a positive experience of care.
Social consequences of psychiatric disorders, I: Educational attainment
Authors: R C Kessler, C L Foster, W B Saunders, P E Stang
Journal: American Journal of Psychiatry (1995)

This is the first in a series of investigations of the social consequences of psychiatric disorders based on the National Comorbidity Survey. Data on the relationship between preexisting psychiatric disorders and subsequent educational attainment are presented.The National Comorbidity Survey is a nationally representative survey of 8,098 respondents in the age range 15-54 years. A subsample of 5,877 respondents completed a structured psychiatric interview and a detailed risk factor battery. Diagnoses of DSM-III-R anxiety disorders, mood disorders, substance use disorders, and conduct disorder were generated, and survival analyses were used to project data on school terminations to the total U.S. population.Early-onset psychiatric disorders are present in more than 3.5 million people in the age range of the National Comorbidity Survey who did not complete high school and close to 4.3 million who did not complete college. The most important disorders are conduct disorder among men and anxiety disorders among women. The proportion of school dropouts with psychiatric disorders has increased dramatically in recent cohorts, and persons with psychiatric disorders currently account for 14.2% of high school dropouts and 4.7% of college dropouts.Early-onset psychiatric disorders probably have a variety of adverse consequences. The results presented here show that truncated educational attainment is one of them. Debate concerning whether society can afford universal insurance coverage for the treatment of mental disorders needs to take these consequences into consideration.
Neoplastic Transformation of Mouse and Hamster Cells &lt;italic&gt;In Vitro&lt;/italic&gt; With and Without Polyoma Virus
Authors: Katherine K. Sanford, Robert E. Hoemann
Journal: JNCI Journal of the National Cancer Institute (1967)

Several cell lines were examined under different culture conditions in an effort to find one that would not undergo "spontaneous" neoplastic transformation but could be transformed by polyoma virus. With such a cell line, large numbers of neoplastic and non-neoplastic cultures might be obtained for comparative studies. Four cell lines derived from different tissues of 2 strains of mice and all 8 lines of cells from 5 different pools of hamster embryo cells underwent spontaneous neoplastic transformation without polyoma virus. However, certain of these lines might be useful, since neoplastic conversion occurred only after prolonged culture. Fairly reproducible neoplastic transformations could be induced by polyoma virus with high multiplicities of infection and rather drastic treatment of cells, including trypsinization. Although it has been postulated that normal Syrian hamster embryo cells have a finite lifespan in vitro, we found that under our culture conditions, continuously growing, non-neoplastic cell lines could be routinely established.
Reference values for the 6-min walk test in healthy subjects 25-55 years old in Bangladesh
Authors: A.K.M. Mosharraf-Hossain, Mohammed Atiqur Rahman
Journal: European Respiratory Journal (2013)

Introduction: The six minute walk test (6MWT) is increasingly accepted worldwide to assess functional exercise capacity of cardiac and pulmonary diseases for its simplicity. Aims and objectives: The aim of the present study was to provide reference values for 6MWD and other primary variables such as oxygen saturation (SpO2), pulse rate (PR) and breathlessness perception done in 6MWT. Methods: We studied a sample of 190 healthy subjects (53 females) of age between 20-50 years (37.9±8.5 years). Baseline lung functions including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio were measured by a flow sensing spirometer. All subjects performed 6MWT according to standard protocol provided by the American Thoracic Society (ATS) guidelines (Am J Respir Crit Care Med 2002;166:111-7). The fatigue and dyspnoea was measured before and after 6MWT by modified Borg scale. The SpO2 and PR were measured also by a light weight pulse oxymeter. Results: The mean 6MWD was 466.7±69.4m, ranging from 213 to 659m and the mean DW was 28732±7024 kg-m. Dyspnoea status and oxygen saturation remained unaltered throughout the walk. Mean resting and walking SpO2 values were, respectively, 97.1±1.3% and 96.8±1.5%. The mean change in SpO2 was .3±1.5%. PR was significantly affected by the walk. Mean resting and maximum PR after walking were respectively, 80±7 and 103±12 bpm (p<.01). Gender significantly affected the 6MWD (p<.01). In all subjects, the 6MWD was inversely and directly related, respectively, to age (r=-.15; P<.05) and height (r=.41; P<.01). Conclusion: This study showed reference values for the 6MWT variables of subjects in Bangladeshi population.
Role of computed tomography in the staging of patients with local-regional metastases of melanoma.
Authors: A C Buzaid, L Tinoco, M I Ross, S S Legha, R S Benjamin
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the value of computed tomographic (CT) scans in the staging of asymptomatic melanoma patients who presented with or developed local-regional disease as the first site of recurrence and had both a normal chest radiograph and serum lactate dehydrogenase (LDH) level. PATIENTS AND METHODS The records of 99 patients with local-regional disease were reviewed. Of these, 89 met the study criteria and are the subjects of this analysis. Radiologic findings were categorized into the following four groups: (1) true-positive (TP), when the scan identified either regional or distant disease that was not appreciated on physical examination; (2) false-positive (FP), when the scan showed a radiologic abnormality that either did not change for at least 6 months or was proven to be histologically benign; (3) false-negative (FN), when a patient had symptoms suggestive of or suspicious for metastases and was subsequently found to have metastases, but all imaging studies were nondiagnostic; and (4) true-negative (TN), when all imaging studies were negative for metastases in an asymptomatic patient. RESULTS Findings on CT scan were TP for six patients (7%), FP for 20 (22%), and TN for 63 (71%). Of the six patients with TP findings, CT of the chest identified disease that was not visible on chest radiograph in only one and CT of the abdomen or pelvis showed metastases in five. CT or magnetic resonance imaging (MRI) of the brain showed no evidence of brain metastases in any patient, although it showed asymptomatic skull metastases in one patient. The most common FP findings were hypodense hepatic lesions and noncalcified lung nodules. CONCLUSION TP findings are observed in approximately 7% of patients with local-regional disease, which indicates a low yield but definite usefulness of CT scans in this subset of patients. Because FP are more common than TP findings, histologic diagnosis of recurrence is advisable. CT scan or MRI of the brain is not necessary in asymptomatic patients. CT of the chest adds little to a chest radiograph. In light of today's more cost-conscious health-care environment, our results are of practical importance.