tbuckley/cabot-search huggingface dataset:
Short burst oxygen therapy after activities of daily living in the home in chronic obstructive pulmonary disease
Authors: S J Quantrill, R White, A Crawford, J S Barry, S Batra, P Whyte, C M Roberts
Journal: Thorax (2007)

Short burst oxygen therapy (SBOT) is widely prescribed in the UK with little evidence of benefit. A study was performed to examine whether SBOT benefits patients when undertaking normal activities at home among those who already use it.Twenty-two patients with chronic obstructive pulmonary disease (COPD) were included in the study. All regularly used SBOT at home and claimed that it helps them. Each patient chose two daily living activities for which they used SBOT for relief of breathlessness. Patients were then randomised to use either an air or oxygen gas cylinder. At least 15 min later the same activity was performed using the other gas cylinder. The same process was then repeated for the second chosen activity. The main endpoints were subjective and objective times to recovery, analysed for each activity separately or taking the average over the two activities. A paired statistical analysis was performed.All patients used SBOT with nasal prongs after exercise. Using the average recovery time over two activities for each patient, the mean objective recovery time was 38 s lower (95% CI -81 to +5) using oxygen and the mean subjective recovery time was 34 s lower (95% CI -69 to +2). Five patients were correctly able to distinguish oxygen from air after both activities and there was a suggestion that their recovery times were shorter than those who did not correctly identify the gases (91 s vs 20 s using objective recovery times, and 80 s vs 22 s using subjective recovery times), although this was a subgroup analysis based on only five patients with non-significant results.There is some evidence that SBOT shortens recovery time after activities of daily living in a selected group of patients with COPD, but the effect is small. There appears to be a subgroup of patients who may benefit to a much greater degree.
The effect of nanoparticles on airway allergy in mice
Authors: K-I. Inoue, H. Takano
Journal: European Respiratory Journal (2011)

To the Editors:

We read with great interest a recent experimental ( in vivo ) study by Hussain et al. 1 and would like to comment on that article. First of all, we were very interested in the overall results that a single airway exposure to relatively low dose (16 μg·mouse−1) of nanoparticles facilitates allergic airway inflammation. We have previously examined several types of nanoparticles/nanomaterials on ovalbumin-induced airway inflammation 2–5. However, the doses were higher (25–100 μg·mouse−1 administered weekly a total of seven times) and provoked a more moderate increase in the number of inflammatory leukocytes into bronchoalveolar spaces in the absence of allergen than that in the present study by Hussain et al. …
Future Directions of Next-Generation Novel Therapies, Combination Approaches, and the Development of Personalized Medicine in Myeloma
Authors: Constantine S. Mitsiades, Faith E. Davies, Jacob P. Laubach, Douglas Joshua, Jesus San Miguel, Kenneth C. Anderson, Paul G. Richardson
Journal: Journal of Clinical Oncology (2011)

Despite tangible progress in recent years, substantial therapeutic challenges remain in multiple myeloma (MM), particularly for patients at high risk for early relapse or death and for those with advanced multi-drug resistant disease and refractoriness to currently available combination regimens. Addressing these challenges requires identification of novel classes of anti-MM agents, their incorporation into safe and more effective combination regimens, and development of efficient algorithms to select the most appropriate therapeutic options for the clinical and molecular features of individual patients at a given time during their disease. Ideally, these goals can be facilitated by preclinical identification of the "driver" molecular lesions on which different myeloma subtypes exquisitely depend, and by informative preclinical models simulating the clinical setting(s) in which trials will be conducted. Large prospective studies of patients treated uniformly with contemporary clinical regimens are essential, but there is also a major need for flexibility in studying new regimens in the future. Long-term patient follow-up and integrated annotation of clinical (safety and efficacy) and correlative (molecular, biochemical, etc) data are also critical. Novel molecular profiling techniques will likely identify more clinically and biologically discrete subsets of patients with recurrent, even if infrequent, lesions. This molecular heterogeneity, combined with the increasing numbers of candidate therapeutic targets and respective investigational agents, may pose formidable challenges for the development and implementation of personalized medicine in MM. This review discusses these challenges, as well as potential strategies to address them, with the aim of making significant improvement in the clinical outcome of patients with MM.
Phase II Trial of Weekly Bortezomib in Combination With Rituximab in Relapsed or Relapsed and Refractory Waldenström Macroglobulinemia
Authors: Irene M. Ghobrial, Fangxin Hong, Swaminathan Padmanabhan, Ashraf Badros, Meghan Rourke, Renee Leduc, Stacey Chuma, Janet Kunsman, Diane Warren, Brianna Harris, Amy Sam, Kenneth C. Anderson, Paul G. Richardson, Steven P. Treon, Edie Weller, Jeffrey Matous
Journal: Journal of Clinical Oncology (2010)

Purpose This study aimed to determine activity and safety of weekly bortezomib and rituximab in patients with relapsed/refractory Waldenström macroglobulinemia (WM). Patients and Methods Patients who had at least one previous therapy were eligible. All patients received bortezomib intravenously weekly at 1.6 mg/m 2 on days 1, 8, and 15, every 28 days for six cycles and rituximab 375 mg/m 2 weekly on cycles 1 and 4. The primary end point was the percentage of patients with at least a minor response. Results Thirty-seven patients were treated. The majority of patients (78%) completed treatment per protocol. At least minimal response (MR) or better was observed in 81% (95% CI, 65% to 92%), with two patients (5%) in complete remission (CR)/near CR, 17 patients (46%) in partial response, and 11 patients (30%) in MR. The median time to progression was 16.4 months (95% CI, 11.4 to 21.1 months). Death occurred in one patient due to viral pneumonia. The most common grade 3 and 4 therapy-related adverse events included reversible neutropenia in 16%, anemia in 11%, and thrombocytopenia in 14%. Grade 3 peripheral neuropathy occurred in only two patients (5%). The median progression-free (PFS) is 15.6 months (95% CI, 11 to 21 months), with estimated 12-month and 18-month PFS of 57% (95% CI, 39% to 75%) and 45% (95% CI, 27% to 63%), respectively. The median overall survival has not been reached. Conclusion The combination of weekly bortezomib and rituximab showed significant activity and minimal neurologic toxicity in patients with relapsed WM.
Coffee, alcohol and other beverages in relation to cirrhosis mortality: The Singapore Chinese Health Study
Authors: George Boon-Bee Goh, Wan-Cheng Chow, Renwei Wang, Jian-Min Yuan, Woon-Puay Koh
Journal: Hepatology (2014)

Limited experimental and epidemiologic data suggest that coffee may reduce hepatic damage in chronic liver disease. The association between consumption of coffee and other beverages and risk of cirrhosis mortality was evaluated in the Singapore Chinese Health Study. This is a prospective population-based cohort of 63,275 middle-aged and older Chinese subjects who provided data on diet, lifestyle, and medical histories through in-person interviews using a structured questionnaire at enrollment between 1993 and 1998. Mortality from cirrhosis in the cohort was ascertained through linkage analysis with nationwide death registry. After a mean follow-up of 14.7 years, 114 subjects died from cirrhosis; 33 of them from viral hepatitis B (29%), two from hepatitis C (2%), and 14 from alcohol-related cirrhosis (12%). Compared to nondrinkers, daily alcohol drinkers had a strong dose-dependent positive association between amount of alcohol and risk of cirrhosis mortality. Conversely, there was a strong dose-dependent inverse association between coffee intake and risk of nonviral hepatitis-related cirrhosis mortality ( P for trend = 0.014). Compared to non-daily coffee drinkers, those who drank two or more cups per day had a 66% reduction in mortality risk (hazard ratio [HR] = 0.34, 95% confidence interval [CI] = 0.14-0.81). However, coffee intake was not associated with hepatitis B-related cirrhosis mortality. The inverse relationship between caffeine intake and nonviral hepatitis-related cirrhosis mortality became null after adjustment for coffee drinking. The consumption of black tea, green tea, fruit juices, or soft drinks was not associated with risk of cirrhosis death. Conclusion : This study demonstrates the protective effect of coffee on nonviral hepatitis-related cirrhosis mortality, and provides further impetus to evaluate coffee as a potential therapeutic agent in patients with cirrhosis. (Hepatology 2014;60:661–669)
The Serum Glycoprotein Fetuin-A Promotes Lewis Lung Carcinoma Tumorigenesis via Adhesive-Dependent and Adhesive-Independent Mechanisms
Authors: Madappa N. Kundranda, Melodie Henderson, Kathy J. Carter, Lee Gorden, Awadh Binhazim, Sanhita Ray, Trevor Baptiste, Masih Shokrani, Maria L. Leite-Browning, Willi Jahnen-Dechent, Lynn M. Matrisian, Josiah Ochieng
Journal: Cancer Research (2005)

Fetuin-A is a serum glycoprotein in the cystatin family associated with the regulation of soft tissue calcification. We tested the role of systemic fetuin in tumor cell growth and metastasis by injecting Lewis lung carcinoma (LLC) cells into fetuin-A null and their wild-type (WT) littermate control C57BL/6 mice via the tail vein, s.c., and intrasplenic routes. In the experimental metastasis assay, the lungs of the WT mice were filled with metastatic nodules, whereas the lungs of the fetuin-A null mutant mice were virtually free of colonies at the end of 2 weeks. Lung colonization responded to the levels of serum fetuin-A in a dose-dependent manner, as observed by the formation of half as many colonies in mice heterozygous for the fetuin-A locus compared with homozygous WT mice and restoration of lung colonization by the administration of purified fetuin-A to fetuin-A-null mice. Serum fetuin-A also influenced the growth of LLC cells injected s.c.: fetuin-A-null mice developed small s.c. tumors only after a substantial delay. Similarly, intrasplenic injection of LLC cells resulted in rapid colonization of the liver with metastasis to the lungs within 2 weeks in the WT but not fetuin-A null mice. To examine the mechanism by which fetuin-A influences LLC colonization and growth, we showed that LLC tumor cells adhere to fetuin-A in a Ca(2+)-dependent fashion, resulting in growth of the tumor cells. These studies support the role of fetuin-A as a major growth promoter in serum that can influence tumor establishment and growth.
Expression of biomarkers modulating prostate cancer angiogenesis: differential expression of annexin II in prostate carcinomas from India and USA.
Authors: Abhijit G Banerjee, Jie Liu, Yawei Yuan, Velliyur K Gopalakrishnan, Sonny L Johansson, Amit K Dinda, Narmada P Gupta, Lindsey Trevino, Jamboor K Vishwanatha
Journal: Molecular Cancer (2003)

Prostate cancer (PCa) incidences vary with genetic, geographical and ethnic dietary background of patients while angiogenesis is modulated through exquisite interplay of tumor-stromal interactions of biological macromolecules. We hypothesized that comprehensive analysis of four biomarkers modulating angiogenesis in PCa progression in two diverse populations might explain the variance in the incidence rates. Immunohistochemical analysis of 42 PCa biopsies reveals that though Anx-II expression is lost in both the Indian and American population with Gleason scores (GS) ranging between 6 and 10, up to 25 % of cells in the entire high grade (GS > 8) PD PCa samples from US show intense focal membrane staining for Anx-II unlike similarly graded specimens from India. Consistent with this observation, the prostate cancer cell lines PC-3, DU-145 and MDA PCa 2A, but not LNCaP-R, LNCAP-UR or MDA PCa 2B cell lines, express Anx-II. Transcriptional reactivation of Anx-II gene with Aza-dC could not entirely account for loss of Anx-II protein in primary PCa. Cyclooxygenase-2 (COX-2) was moderately expressed in most of high grade PIN and some MD PCa and surrounding stroma. COX-2 was not expressed in PD PCa (GS ~7–10), while adjacent smooth muscles cells stained weakly positive. Decorin expression was observed only in high grade PIN but not in any of the prostate cancers, atrophy or BPH while stromal areas of BPH stained intensively for DCN and decreased with advancing stages of PCa. Versican expression was weak in most of the MD PCa, moderate in all of BPH, moderately focal in PD PC, weak and focal in PIN, atrophy and adjacent stroma. Expression of pro- and anti-angiogenic modulators changes with stage of PCa but correlates with angiogenic status. Focal membrane staining of Anx-II reappears in high grade PCa specimens only from US indicating differential expression of Anx-II. COX-2 stained stronger in American specimens compared to Indian specimens. The sequential expression of DCN and VCN in progressive stages was similar in specimens from India and USA indicating no population-based differences. The mechanistic and regulatory role of Anx-II in PCa progression warrants further investigation.
Molecular Profiling of Tumor Cells in Cerebrospinal Fluid and Matched Primary Tumors from Metastatic Breast Cancer Patients with Leptomeningeal Carcinomatosis
Authors: Mark Jesus M. Magbanua, Michelle Melisko, Ritu Roy, Eduardo V. Sosa, Louai Hauranieh, Andrea Kablanian, Lauren E. Eisenbud, Artem Ryazantsev, Alfred Au, Janet H. Scott, John W. Park
Journal: Cancer Research (2013)

Although leptomeningeal carcinomatosis is a well-established clinical syndrome, virtually nothing is known about the tumor cells responsible for this particularly aggressive metastatic process. To isolate cerebrospinal fluid-derived tumor cells (CSFTC) from 15 patients with metastatic breast cancer diagnosed with leptomeningeal carcinomatosis, CSF samples were subjected to a two-step method involving immunomagnetic enrichment and fluorescence-activated cell sorting (IE/FACS), a technique previously used for isolating circulating tumor cells (CTC) from blood. CSFTCs were subjected to genome-wide copy number analysis by array comparative genomic hybridization. Genomic profiling was successfully performed for 13 of 15 patients (87%). Copy number analysis in CSFTCs revealed genomic alterations commonly observed in primary breast cancer and CTCs, indicating their malignant origin. Interestingly, 12 (92%) harbored high-level gains on the 8q24 locus, which includes the MYC oncogene. Comparison of CSFTCs against corresponding archival primary tumors in six patients revealed clonal relationships with some divergence. Good concordance among serial samples attested to the reproducibility of the assay. Our approach for isolation and molecular analysis of CSFTCs yielded new insights into the molecular nature of these cells. Further genomic and functional analyses may help elucidate mechanisms by which tumor cells metastasize to the central nervous system.
Spontaneous pneumomediastinum in patients with severe acute respiratory syndrome
Authors: C.M. Chu, Y.Y. Leung, J.Y.H. Hui, I.F.N. Hung, V.L. Chan, W.S. Leung, K.I. Law, C.S. Chan, K.S. Chan, K.Y. Yuen
Journal: European Respiratory Journal (2004)

Spontaneous pneumomediastinum (SP) unrelated to assisted ventilation is a newly recognised complication of severe acute respiratory syndrome (SARS). The objective of the present study was to examine the incidence, risk factors and the outcomes of SP in a cohort of SARS victims from a community outbreak. Data were retrieved from a prospectively collected database of virologically confirmed SARS patients. One hundred and twelve cases were analysable, with 13 patients developing SP (11.6%) at a mean +/- SD of 19.6 +/- 4.6 days from symptom onset. Peak lactate dehydrogenase level was associated with the development of SP. SP was associated with increased intubation and a trend towards death. Drainage was required in five cases. For patients who survived, the SP and/or the associated pneumothoraces took a median of 28 days (interquartile range: 15-45 days) to resolve completely. In conclusion, spontaneous pneumomediastinum appeared to be a frequent complication of severe acute respiratory syndrome. Further research is needed to investigate its pathogenesis.
Mycosis fungoides in young patients: Clinical characteristics and outcome
Authors: Jeffrey J. Crowley, Anthony Nikko, Anna Varghese, Richard T. Hoppe, Youn H. Kim
Journal: Journal of the American Academy of Dermatology (1998)

<h2>Abstract</h2> <b>Background:</b> Mycosis fungoides (MF) can begin as early as the first decade of life. Few studies have reviewed MF in younger patients and none has been large enough to assess prognosis and outcome. <b>Objective:</b> We reviewed the clinical characteristics, prognosis, factors related to disease progression, and therapy in patients with MF younger than 35 years of age. <b>Methods:</b> Fifty-eight patients were entered into this retrospective cohort analysis. <b>Results:</b> Significantly fewer patients with MF who are younger than 35 years presented with erythroderma (T4) and more with limited patch/plaque (T1) disease than older patients. Duration of skin disease before diagnosis of MF did not vary between the two groups. The long-term survival of younger patients with MF is significantly decreased when compared with a race-, age-, and sex-matched control population (<i>p</i> < 0.001). Disease-specific survivals (DSS) of younger and older patients are similar, but young patients show a slight but significantly better overall DSS (<i>p</i> < 0.02). However, DSS comparison of generalized patch/plaque (T2) and tumor stage (T3) patients with MF showed no significant difference between young and old patients (<i>p</i> = 0.47, <i>p</i> = 0.59). Patient age was not a significant predictor of survival when controlled for T-stage. Sixteen of 58 young patients with MF have died, 13 because of MF (22%), compared with 138 of 500 older patients (28%) who died as a result of MF. All younger patients with MF who progressed had at least T2 disease at presentation. Fifty of 56 young patients with MF and T1-T3 disease were treated initially with total skin electron beam or topical nitrogen mustard. The response to therapy was similar in younger and older patients with MF. <b>Conclusion:</b> T1 disease is more common and T4 disease is unusual in young patients with MF compared with an older population of patients with MF. Young patients with T1 disease, all of whom were treated with either topical nitrogen mustard or total skin electron beam therapy, or both therapies, showed no disease progression. Overall, young patients with MF showed slightly better DSS, but this was because of differences in stage distribution.(J Am Acad Dermatol 1998;38:696-701.)
rhDNase in cystic fibrosis
Authors: J C TYRRELL, P A LEWIS, C D SHELDON, G CONNETT
Journal: Thorax (1999)

We agree with Richard Coker 1 that the vast majority of non-compliant cases of tuberculosis can be dealt with by a mixture of directly observed therapy (DOT) and inducements.However, when DOT fails in a few cases each year, despite intensive team eVort and carrots such as housing or food vouchers, the Public Health Act may have to be invoked.We have had recourse to this measure four times in the past six months but, though providing valuable breathing space, it is extremely costly and proved ineVectual as a solution each time.Once the patient is admitted there are still potential problems.Treatment cannot be enforced and patients can abscond.There have also been instances of patients assaulting staV, physically and sexually, issuing death threats, breaking hospital property, and terrorising other patients, even interfering with others' oxygen therapy.Dealing with such patients puts hospital staV and patients under unacceptable pressure and requires extra staYng for security purposes.NHS hospitals were not designed for, nor are they staVed adequately for, custodial purposes.There is an urgent need to review the Public Health Act and make provisions for small specialist units staVed by nurses with training in and an aptitude for interpersonal skills.Admission to the unit would usually only be required for short periods of time until precipitating circumstances were resolved and alternative arrangements made.The threat of compulsory admission, or a short period thereof, may induce a behavioural change in the patient, allowing DOT to be successful after failing previously.In addition, a centrally based mobile unit of trained staV could be available to help tide teams over emergencies and could reduce the need for the specialist unit, enabling more non-adherent patients to be managed in the community.We call upon the Department of Health to examine and implement these proposals.
CD40 activation of BCP-ALL cells generates IL-10–producing, IL-12–defective APCs that induce allogeneic T-cell anergy
Authors: Giovanna D'Amico, Marisa Vulcano, Cristina Bugarin, Giancarlo Bianchi, Gisella Pirovano, Martin Bonamino, Virna Marin, Paola Allavena, Ettore Biagi, Andrea Biondi
Journal: Blood (2004)
Effects of upper respiratory tract infections in patients with cystic fibrosis.
Authors: J Collinson, K G Nicholson, E Cancio, J Ashman, D C Ireland, V Hammersley, J Kent, C O'Callaghan
Journal: Thorax (1996)

The polymerase chain reaction has improved the detection of picornaviruses and rhinoviruses and our understanding of their role in reversible airways disease. The effects of colds on lower respiratory morbidity and bacterial colonisation in cystic fibrosis remain uncertain.Children with cystic fibrosis were evaluated regularly in the clinic and the parents notified the investigators when their child developed a cold. Nasopharyngeal specimens were collected at the start of the infection for polymerase chain reaction, bacteriology was also undertaken and again three weeks later, and pulmonary function was measured in children aged > or = 6 years at four day intervals for three weeks. The effects of colds on rate of progression of cystic fibrosis were assessed by pulmonary function, Shwachman scores, and radiology.Thirty eight children suffered 147 colds over 17 months. Picornaviruses were detected in 51 (43%) of 119 nasopharyngeal specimens, and 21 of the 51 were further identified as rhinoviruses. Pulmonary dysfunction was similar following picornavirus and non-picornavirus infections; the mean change from baseline in forced expiratory volume in one second (FEV1) was -16.5% and -10.3% at 1-4 days and 21-24 days, respectively, after onset of a cold. Children who experienced more colds than average had evidence of disease progression with reduction in Shwachman score, increasing Chrispin-Norman score, and greater deterioration in FEV1 per annum. Ten of 12 new bacterial infections were associated with a cold.Picornavirus and non-picornavirus colds are associated with pulmonary function abnormalities and disease progression in patients with cystic fibrosis, and predispose to secondary bacterial infection and colonisation.
Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study
Authors: Luke Hunt, Ankur Gupta-Wright, Victoria Simms, Fayia Tamba, Victoria Knott, Kongoneh Tamba, Saidu Heisenberg-Mansaray, Emmanuel Tamba, Alpha Sheriff, Sulaiman Conteh, Tom Smith, Shelagh Tobin, Tim Brooks, Catherine Houlihan, Rachael Cummings, Tom Fletcher
Journal: The Lancet Infectious Diseases (2015)