tbuckley/cabot-search huggingface dataset:
Effect of Tumor Host Microenvironment on Photodynamic Therapy in a Rat Prostate Tumor Model
Authors: Bin Chen, Brian W. Pogue, Xiaodong Zhou, Julia A. O'Hara, Nicolas Solban, Eugene Demidenko, P. Jack Hoopes, Tayyaba Hasan
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Tumor host microenvironment plays an important role in tumor growth, metastasis, and response to cancer therapy. In this study, the influence of tumor host environment on tumor pathophysiology, photosensitizer distribution, and photodynamic therapy (PDT) treatment effect was examined in the metastatic at lymph node and lung (MatLyLu) rat prostate tumor. Experimental Design: MatLyLu tumors implanted in different host environment [i.e., orthotopically (in the prostate) or s.c.] were compared for difference in vessel density, average vessel size, vascular permeability, tumor vascular endothelial growth factor production, and tumor oxygenation. Uptake of photosensitizer verteporfin in tumors in both sites was determined by fluorescence microscopy. To compare tumor response to PDT, both orthotopic and s.c. MatLyLu tumors were given the same doses of verteporfin and laser light treatment, and PDT-induced tumor necrotic area was measured histologically. Results: Orthotopic MatLyLu tumors were found to grow faster, have higher vessel density and more permeable vasculature, have higher vascular endothelial growth factor protein levels, and have lower tumor hypoxic fraction than the s.c. tumors. Uptake of photosensitizer verteporfin in the orthotopic tumor was higher than in the s.c. tumors at 15 minutes after injection (1 mg/kg, i.v.), and became similar at 3 hours after injection. For the vascular targeting PDT treatment (0.25 mg/kg verteporfin, 50 J/cm2 at 50 mW/cm2, 15 minutes drug-light interval), there was no significant difference in PDT-induced tumor necrotic area between the orthotopic and s.c. tumors, with 85% to 90% necrosis in both types of tumors. However, tumor necrosis induced by the cellular targeting PDT (1 mg/kg verteporfin, 50 J/cm2 at 50 mW/cm2, 3 hours drug-light interval) was significantly different in the orthotopic (64%) versus the s.c. (29%) tumors. Conclusions: Tumor host environment can significantly affect photosensitizer verteporfin distribution and PDT treatment effect. Verteporfin-PDT regimen targeting tumor cells is more sensitive to such influence than the vascular targeting PDT. Our study showed the importance of tumor host environment in determining tumor physiologic properties and tumor response to PDT. To obtain clinically relevant information, orthotopic tumor model should be used in the experimental studies.
Phase III, Multicenter, Double-Blind, Randomized Study of Letrozole, an Aromatase Inhibitor, for Advanced Breast Cancer Versus Megestrol Acetate
Authors: A. Buzdar, J. Douma, N. Davidson, R. Elledge, M. Morgan, R. Smith, L. Porter, J. Nabholtz, X. Xiang, C. Brady
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To compare two doses of letrozole (0.5 mg and 2.5 mg every day) and megestrol acetate (40 mg qid) as endocrine therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: This double-blind, randomized, multicenter, multinational study enrolled 602 patients, all of whom were included in the primary analysis in the protocol. Patients had advanced or metastatic breast cancer with evidence of disease progression while receiving continuous adjuvant antiestrogen therapy, had experienced relapse within 12 months of stopping adjuvant antiestrogen therapy given for at least 6 months, or had experienced disease progression while receiving antiestrogen therapy for advanced disease. Tumors were required to be estrogen receptor– and/or progesterone receptor–positive or of unknown status. Confirmed objective response rate was the primary efficacy variable. Karnofsky Performance Status and European Organization for Research and Treatment of Cancer quality-of-life assessments were collected for 1 year. RESULTS: There were no statistically significant differences among the three treatment groups for overall objective tumor response. Patients treated with letrozole 0.5 mg had improvements in disease progression (P = .044) and a decreased risk of treatment failure (P = .018), compared with patients treated with megestrol acetate. Letrozole 0.5 mg showed a trend (P = .053) for survival benefit when compared with megestrol acetate. Megestrol acetate was more likely to produce weight gain, dyspnea, and vaginal bleeding, and the letrozole groups were more likely to experience headache, hair thinning, and diarrhea. CONCLUSION: Given a favorable tolerability profile, once-daily dosing, and evidence of clinically relevant benefit, letrozole is equivalent to megestrol acetate and should be considered for use as an alternative treatment of advanced breast cancer in postmenopausal women after treatment failure with antiestrogens.
Do Routine Clinic Visits Prevent De-Stabilization in Patients Awaiting Coronary Revascularization?
Authors: R Lim, I Kreidieh, D S Dymond
Journal: Journal of the Royal Society of Medicine (1991)

We examined retrospectively the usefulness of routine clinic visits in preventing adverse cardiac events in 115 patients awaiting coronary surgery or angioplasty. Mean waiting time from angiography to revascularization was 126 days. A total of 126 visits were made by 80 patients. No deaths occurred, but one patient, despite three visits, suffered myocardial infarction at 316 days post-angiography. Eight patients required admission for unstable angina, five having been on the waiting list for less than 5 weeks. The mean number of clinic visits, number of diseased vessels and proportion on triple anti-ischaemic therapy were similar in the patients suffering such events and those remaining stable. In conclusion, the inherent unpredictability of coronary disease greatly limits the role of interim clinic visits in the prevention of adverse cardiac events in patients awaiting revascularization.
Medicare outcomes have improved markedly over past two decades, study indicates
Authors: Michael McCarthy
Journal: BMJ (2015)

Over the past two decades mortality and admissions to hospital have fallen markedly among Medicare patients, while health outcomes have improved, a new study has reported.1 The study appears in this week’s issue of the Journal of the American Medical Association ( JAMA ), which features articles marking Medicare’s 50th anniversary.

In an audio summary accompanying the paper, the lead author, Harlan M Krumholz, of Yale University School of Medicine in New Haven, Connecticut, said that the report “suggests we are in the midst of a remarkable improvement in health and healthcare.” 

“The improvements we observed were extraordinarily broad based,” Krumholz added. “We looked at various different subgroups: we looked by age, we looked by sex, …
Recombinant Human Gamma-Interferon in Primary Hepatocellular Carcinoma
Authors: Alastair Forbes, Philip J Johnson, Roger Williams
Journal: Journal of the Royal Society of Medicine (1985)

A phase II trial of recombinant human gamma-interferon in the treatment of unresectable primary hepatocellular carcinoma is reported. The trial was terminated prematurely after recruitment of only 7 patients because of unacceptable toxicity, predominantly renal. There was no evidence of response in any of the 7 patients but some evidence that disease progression was more rapid during the treatment period.
Optimal Medical Therapy With or Without Percutaneous Coronary Intervention in Older Patients With Stable Coronary Disease
Authors: Koon K. Teo, Steven P. Sedlis, William E. Boden, Robert A. O'Rourke, David J. Maron, Pamela M. Hartigan, Marcin Dada, Vipul Gupta, John A. Spertus, William J. Kostuk, Daniel S. Berman, Leslee J. Shaw, Bernard R. Chaitman, G.B. John Mancini, William S. Weintraub
Journal: Journal of the American College of Cardiology (2009)
Candidaemia in a European Paediatric University Hospital: a 10-year observational study
Authors: A. Tragiannidis, W. Fegeler, G. Rellensmann, V. Debus, V. Müller, I. Hoernig-Franz, K. Siam, Z.-D. Pana, H. Jürgens, A.H. Groll
Journal: Clinical Microbiology and Infection (2011)
Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer.
Authors: D C Ihde, J L Mulshine, B S Kramer, S M Steinberg, R I Linnoila, A F Gazdar, M Edison, R M Phelps, M Lesar, J C Phares
Journal: Journal of Clinical Oncology (1994)

PURPOSE We performed a prospective randomized clinical trial to determine whether higher doses of etoposide and cisplatin (EP) yield more complete responses or longer survival in small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS Ninety patients with previously untreated extensive-stage SCLC fulfilled criteria for randomization to standard-dose versus high-dose EP. Another 25 patients at risk of excessive toxicity from high-dose treatment were given standard-dose therapy. During cycles 1 and 2 of EP, patients on standard-dose treatment received intravenous etoposide 80 mg/m2 on days 1 to 3 and cisplatin 80 mg/m2 on day 1 every 3 weeks; high-dose treatment consisted of etoposide 80 mg/m2 on days 1 to 5 and cisplatin 27 mg/m2 on days 1 to 5 every 3 weeks. All patients received standard-dose EP in cycles 3 and 4. In cycles 5 through 8, completely responding patients continued standard-dose EP; all other patients received either cyclophosphamide, doxorubicin, and vincristine, or (if possible) a combination drug program based on in vitro drug sensitivity testing of tumor-cell lines established from individual patients. RESULTS Despite 68% higher doses and a 46% higher dose-rate intensity actually given to patients randomized to receive high-dose relative to those randomized to receive standard-dose EP, complete response rates (23% v 22%; P = .99) and median survival durations (10.7 and 11.4 months, respectively; P = .68) were virtually identical. Complete responses occurred in 4% of patients and the median survival duration was 5.8 months in nonrandomized patients. Leukopenia (P &lt; .0001), thrombocytopenia (P &lt; .0001), febrile neutropenia (P = .01), and weight loss (P = .02) were significantly more common in patients randomized to receive high-dose compared with standard-dose EP. CONCLUSION No therapeutic benefits resulted from increasing planned doses by 67% for the first two cycles of EP in patients with extensive-stage SCLC. Higher doses were associated with substantially worse toxicities.
Outcome of patients with interstitial lung disease admitted into ICU
Authors: Amandine Vial-Dupuy, Olivier Sanchez, Liath Guetta, Benoit Douvry, Karine Juvin, Delphine Wermert, Emmanuel Guerot, Dominique Israel-Biet
Journal: European Respiratory Journal (2011)

Background:  Limited data are available on the clinical course of patients with Interstitial Lung Disease (ILD) and acute respiratory failure requiring admission to ICU.   Objectives:  To investigate the outcome of patients with ILD and acute respiratory failure with special attention to Idiopathic Pulmonary Fibrosis (IPF) or Drug-induced ILD (DI-ILD).   Methods:  Retrospective identification of patients with ILD admitted into ICU between 1993 and 2009. Primary end-point was in-hospital mortality.   Results:  72 subjects could be included, divided into 3 groups: IPF, n=28; DI-ILD, n=20 and Miscellaneous, n=24. The in-hospital mortality rates were 68, 40 and 25% for IPF, DI-ILD and Miscellaneous, respectively, (p=0.006) and reached 100, 64 and 60%, respectively, in those receiving mechanical ventilation (p=0.007).  On multivariate analysis, the need for invasive or non invasive ventilation (OR= 35; [95% IC, 5-255]), the type of ILD (IPF vs Miscellaneous) (OR=22; [95% IC, 3-147]), and high-dose steroids during ICU stay (OR=0.19; [95% IC, 0.04-0.99]) were found to be independent determinants of in-hospital mortality.   Conclusion:  This study highlights the poor prognosis of IPF in ICU particularly if mechanical ventilation is required. DI-ILD and Miscellaneous with comparable severity criteria have a better prognosis than IPF. High-dose steroids appear as a protective factor whatever the type of ILD.
Are we recording peak flows properly in young children?
Authors: A Greenough, L Everett, JF Price
Journal: European Respiratory Journal (1990)

Peak flow rate is used in young children to assess bronchodilator response and monitor asthma status at home. Frequently the best of only three peak flow manoeuvres is reported. The aim of this study was to assess if this was sufficient to give the maximum peak flow rate and to determine the reproducibility of the measurement. Thirty nine children aged between three and ten years were recruited. Peak expiratory flow rate (PEFR) was measured six times in each child at two minute intervals. Less than half (13 of 39) of the children made their maximum blow in the first three manoeuvres. The maximum peak flow from the second set of three blows was a median of 7% greater than that from the first three blows. The coefficient of variation of the measurement was 8.8% suggesting a change in PEFR greater than 17.6% is necessary to demonstrate a response to bronchodilator. We conclude three peak flow manoeuvres are insufficient in the majority of young children to demonstrate the maximum peak flow.
Prospective Study of <i>Helicobacter pylori</i> Eradication Therapy in Stage I<sub>E</sub> High-Grade Mucosa-Associated Lymphoid Tissue Lymphoma of the Stomach
Authors: Li-Tzong Chen, Jaw-Town Lin, Rong-Yaun Shyu, Chang-Ming Jan, Chi-Long Chen, I-Ping Chiang, Shiang-Ming Liu, Ih-Jen Su, Ann-Lii Cheng
Journal: Journal of Clinical Oncology (2001)

PURPOSE: High-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach are generally believed to be Helicobacter pylori–independent, autonomously growing tumors. However, anecdotal cases of regression of high-grade lymphomas after the cure of H pylori infection had been described. The present prospective study was conducted to evaluate the effect of anti–H pylori therapy in stage I E high-grade gastric MALT lymphomas. PATIENTS AND METHODS: Sixteen patients with H pylori infection and stage I E gastric high-grade MALT lymphoma consented to a brief antibiotic therapy as first-line treatment from June 1995 through April 2000. Then, patients underwent intensive endoscopic follow-up examinations (± endoscopic ultrasonography) with biopsy to evaluate tumor response. Patients with significant improvement of gross lesions that accompanied regression of large cells were followed up without additional treatment. Patients without significant improvement were immediately referred to systemic chemotherapy. RESULTS: Eradication of H pylori was achieved in 15 patients and was accompanied by rapid gross tumor regression and disappearance of large cells in 10. All 10 of these patients with early response had subsequent complete histologic remission of lymphoma. The complete remission rate was 62.5% (95% confidence interval, 35.8% to 89.1%). The response rate was not affected by the tumor grading (proportion of large blast cells within the tumor) but was adversely affected by the depth of tumor invasion. At a median follow-up of 43.5 months (range, 21.1 to 67.4 months), all 10 of these patients remained lymphoma-free. The median duration of complete response was 31.2 months (range, 14.4 to 49.1 months). CONCLUSION: These results suggest that high-grade transformation is not necessarily associated with the loss of H pyloridependence in early-stage MALT lymphomas of the stomach.
Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer.
Authors: D Fennelly, C Aghajanian, F Shapiro, C O'Flaherty, M McKenzie, C O'Connor, W Tong, L Norton, D Spriggs
Journal: Journal of Clinical Oncology (1997)

Paclitaxel has shown significant activity in advanced ovarian cancer. In vitro studies with paclitaxel have suggested that fractionated brief infusion schedules may be more effective than the standard 24-hour infusion. We commenced a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m2) administered weekly as a 1-hour infusion in patients with recurrent ovarian cancer. All patients had received prior paclitaxel and cisplatin therapy. All patients received standard premedication.Eighteen patients are assessable on this phase I study. The mean age was 54 years (range, 48 to 74). The median number of prior chemotherapy regimens was three (range, two to five). The mean paclitaxel-free interval was 10.1 months (range, 1 to 24).A total of 194 cycles of therapy were administered, with a mean of 10 (range, one to 12) per patient. No mucositis or grade III neuropathy was seen. Alopecia occurred in one out of 18 assessable patients. The mean neutrophil nadir was 4.0 x 10(9)/L. At the top dose level (100 mg/m2) delivered, dose-intensity was 90.75% of that planned and greater than two fold the standard dose-intensity. Partial responses were seen in four of 13 assessable patients (30%). Two patients with progression of disease on standard three-week paclitaxel schedules switched to a weekly schedule with demonstrated response. Increasing paclitaxel dose correlated with measured area under the curve (AUC) (R2 = .614). Dose-limiting toxicity was reached at 100 mg/m2 with two of three patients experiencing a treatment delay, thus defining a maximum-tolerated dose of 80 mg/m2 in this group of heavily pretreated patients on this weekly schedule.(1) Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule of administration does not result in cumulative myelosuppression; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile.
Blinded by the light.
Authors: P McCrory
Journal: British Journal of Sports Medicine (2004)

A recent American film— 21 grams —made the assertion that at the precise moment of death each of us loses 21 grams of weight. My curiosity was aroused by this startling claim. Given that more than 2 million Americans claim to have been abducted by aliens at some stage in their lives, I assumed that this rather extraordinary statement was simply more American bunkum.

Believe it or not, such an experiment was actually carried out. In 1907, Duncan MacDougall MD of Haversham, Massachusetts performed a series of extraordinary experiments on dying patients. 1 He reported six …
Persistent asthma, comorbid conditions and the risk of work disability: a prospective cohort study
Authors: R. Hakola, P. Kauppi, T. Leino, A. Ojajärvi, J. Pentti, T. Oksanen, T. Haahtela, M. Kivimäki, J. Vahtera
Journal: Allergy (2011)

This study examined whether asthma alone or together with chronic comorbidity is associated with an increased risk of long-term work disability.We examined data from 2332 asthmatic and 66 354 nonasthmatic public sector employees in Finland who responded to a survey between 1997 and 2004. Respondents were coded as persistent asthmatics based on the special reimbursement for continuous asthma medication by the Social Insurance Institution. Data on long-term work disability (sickness absences or disability pensions > 90 days) were obtained from national registers. The risk of work disability was examined by Cox proportional hazard models adjusted for age, gender, socioeconomic status, type of employment contract, and type of employer.Asthma increased the risk of all-cause long-term work disability with hazard ratio (HR) 1.8 (95% CI 1.62-2.09) compared with controls (no asthma). Asthma and one other chronic comorbidity increased the risk of long-term all-cause work disability with HR 2.2 (95% CI 1.78-2.83). Asthma together with two or more other chronic conditions increased the risk with HR 4.5 (95% CI 2.98-6.78). Asthma and depression increased the risk with HR 3.6, and the risk was especially high for permanent work disability (HR 6.8). Among those with asthma, there were more women, obese individuals (BMI ≥ 30), ex-smokers, and lower-grade nonmanual workers.Asthma is associated with an increased risk of long-term all-cause work disability. The risk increases further with chronic comorbidities and is especially high in patients with asthma and depression.
Screening for alpha-1 antitrypsin deficiency in Polish lung or liver disease patients
Authors: Radoslaw Struniawski, Pawel Kuca, Adam Szpechcinski, Michal Skronski, Malgorzata Czajkowska-Malinowska, Jerzy Kozielski, Pawel Sliwinski, Katarzyna Gόrska, Piotr Korczynski, Rafal Krenke, Ryszarda Chazan, Urszula Oldakowska-Jedynak, Marek Krawczyk, Ewa Jassem, Halina Batura-Gabryel, Joanna Chorostowska-Wynimko
Journal: European Respiratory Journal (2011)

Background:  In Poland, the overwhelming majority of individuals with alpha-1 antitrypsin (AAT) deficiency still remains undiagnosed. We estimated the AAT gene frequency and prevalence in a large cohort of Polish chronic lung or liver disease patients eligible for AAT testing.   Methods:  Blood samples were collected prospectively from 419 respiratory patients (COPD, emphysema, bronchiectasis, asthma) and 281 patients referred for liver transplantation due to cirrhotic and non-cirrhotic chronic disease. AAT serum concentration was measured by turbidimetry and PI-phenotype identified by isoelectrofocusing. The PI*S and PI*Z alleles were confirmed by real-time PCR; rare phenotypes were identified by sequencing.   Results:  53 (12.6%) lung disease patients and 18 (6.4%) liver disease patients demonstrated AAT deficiency phenotypes. Calculated frequencies expressed per 1000 were for PI*Z 46.6 (95% CI: 32.3-60.8), PI*S 20,3 (95% CI: 10.8-29.8) in respiratory patients and PI*Z 19.6 (95% CI: 8.1-31), PI*S 10.7 (95% CI: 2.2-19.2) in liver disease patients. The AAT gene prevalence calculated by Hardy-Weinberg equilibrium were: 1/1.16 for MM, 1/26 for MS, 1/2429 for SS, 1/11 for MZ, 1/530 for SZ and 1/462 for ZZ in respiratory patients and 1/1.07 for MM, 1/48 for MS, 1/8773 for SS, 1/26 for MZ, 1/2393 for SZ and 1/2610 for ZZ in liver disease patients.   Conclusion:  Our results show relatively high frequency of AAT deficiency among Polish patients with chronic obstructive respiratory disorders. Estimated frequency for PI*Z and PI*S allele in respiratory group was about two-fold higher than in liver disease patients and four-fold higher than estimated prevalence in healthy Polish population.
High Resolution Imaging of the Upper Respiratory Tract with Optical Coherence Tomography
Authors: COSTAS PITRIS, MARK E. BREZINSKI, BRETT E. BOUMA, GARY J. TEARNEY, JAMES F. SOUTHERN, JAMES G. FUJIMOTO
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

A need exists in respiratory medicine for a technology capable of identifying airway pathology on a micron scale. This study has demonstrated the feasibility of optical coherence tomography (OCT) for ultrahigh resolution imaging of the upper respiratory tract by in vitro studies of human tissue. OCT is a relatively new technique that can be used to noninvasively collect tomographic images of tissue microstructure with micron-scale resolution. OCT is analogous to ultrasound, measuring the intensity of infrared light rather than acoustical waves. Samples throughout the upper respiratory tract, from the epiglottis to the secondary bronchi, were imaged. The resulting images were compared with histopathology and verified the ability of OCT to delineate relevant structures such as the epithelium, mucosa, cartilage and its sublayers, and glands at a resolution higher than any clinical imaging technology. The ability of OCT to generate image resolution in the range close to that of histopathology in real time, as well as easy integration with small, relatively inexpensive endoscopes, low cost, and lack of a need for a transducing medium, supports the hypothesis that this optical technology could become a powerful modality in the diagnosis and management of a wide range of clinical respiratory pathology.