tbuckley/cabot-search huggingface dataset:
Treatment of cancer with radiation and drugs.
Authors: I F Tannock
Journal: Journal of Clinical Oncology (1996)

PURPOSE To review the current status and future prospects of combined treatment of cancer with radiation and drugs. DESIGN A review of (1) mechanisms whereby combined use of radiation and drugs might lead to improved therapeutic benefit for the treatment of cancer; (2) problems related to the design and analysis of clinical trials that evaluate combined modality treatment; and (3) clinical results of larger randomized trials that have compared combined versus single modality treatment for various types of cancer. RESULTS Improvement in the therapeutic index depends on exploitation of the biologic properties that differ between tumors and normal tissues; such properties may include mechanisms of resistance to radiation and drugs, tissue microenvironment, and cell proliferation or repopulation during radiotherapy. To detect or rule out the small but clinically important differences in outcome that might occur will require the performance of large, randomized, controlled trials or patient-based meta-analyses; single-arm studies, small randomized trials, and subgroup analyses of larger trials can generate hypotheses. Clinical gains from combined treatment have been demonstrated in a few sites, with disappointing results in others. In general, more promising results have accrued from concurrent treatment, despite greater toxicity, than from sequential use of drugs and radiation. CONCLUSION Clinical gains from combined treatment with radiation and drugs have been small. New, mechanistically based approaches to combined treatment are required.
Reduced incidence of pneumonia in influenza-vaccinated solid organ transplant recipients with influenza disease
Authors: P. Perez-Romero, T.A. Aydillo, A. Perez-Ordonez, P. Mufioz, A. Moreno, F. Lopez-Medrano, M. Bodro, M. Montejo, J. Gavalda, M. Carmen Fariñas, J. Pachon, E. Cordero
Journal: Clinical Microbiology and Infection (2012)
Assessment of a Combined Panel of Six Serum Tumor Markers for Lung Cancer
Authors: Rafael Molina, Ramon M. Marrades, Josep Maria Augé, Jose M. Escudero, Nuria Viñolas, Noemi Reguart, Jose Ramirez, Xavier Filella, Laureano Molins, Alvar Agustí
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: We have previously identified six serum tumor markers (TMs) (carcinoembryonic antigen, carbohydrate antigen 15.3, squamous cell carcinoma–associated antigen, cytokeratin-19 fragment, neuron-specific enolase, and pro–gastrin-releasing peptide) related to the presence of lung cancer (LC).Objectives: To validate their individual performance in an independent cohort, and to explore if their combined assessment (≥1 abnormal TM value) is a more accurate marker for LC presence.Methods: We determined these six TMs in 3,144 consecutive individuals referred to our institution by their primary care physician because of the clinical suspicion of LC.Measurements and Main Results: LC was excluded in 1,316 individuals and confirmed in 1,828 patients (1,563 with non–small cell LC and 265 with small cell LC). This study validated the previously reported performance of each individual TM. We also showed that their combined assessment (≥1 abnormal TM) had a better sensitivity, specificity, negative predictive value, and positive predictive value (88.5, 82, 83.7, and 87.3%, respectively) than each TM considered individually and that it increased the diagnostic performance (area under the curve) of a clinical model that included tumor size, age, and smoking status. In patients with radiographic nodules less than 3 cm, the negative predictive value of the TM panel was 71.8%, hence providing some support for a more conservative diagnostic approach. Finally we identified two TMs (neuron-specific enolase and pro–gastrin-releasing peptide) that differentiate the risk of non–small cell LC from that of small cell LC.Conclusions: The combined assessment of a panel of six serum TMs is a more accurate marker for LC presence than these same TMs considered individually. The potential of these TMs in the diagnostic and screening settings deserves further research.
Randomized short-term trial of high span versus low span APAP for the treatment of obstructive sleep apnea
Authors: Helder Novais e Bastos, Ana Sofia Castro, Tiago Pinto, Anabela Marinho, Maria Sucena, Marta Drummond, João Almeida, João Winck
Journal: European Respiratory Journal (2013)

Background: Auto-titrating continuous positive airway pressure (APAP) devices have been developed to improve efficacy and compliance to treatment of patients with obstructive sleep apnea syndrome (OSAS). Since there are insufficient data on the optimal pressure range setting, we aimed in this study to compare the efficacy of treatment with high span versus low span APAP.  Methods: Fifty-three newly diagnosed OSAS patients fulfilling the treatment criteria were randomized to receive high span (HS, range 4-15 cmH2O, n=25) or low span (LS, range 8-12 cmH2O, n=28) APAP. Patients were assessed at 1 and 3 months.  Results: Mean (±SD) Epworth Sleepiness Scale (ESS) was 10.5±6.2 and median apnea-hypopnea index (AHI) was 31.9 (IQR, 23.1-46.4). There were no significant differences in gender distribution, age, body-mass index, cervical perimeter, ESS and AHI between groups. Overall, no significant differences were found at the 1st month assessment. After 3 months of APAP therapy, we again found no differences in air leakage or residual AHI. However, HS group proved less adherent than LS group, respectively with median 69.5% (IQR, 44-96) vs 96% (IQR, 83.5-98) of the nights using at least 4h (p=0.008) and mean usage 5.4±1.8 h/night vs 6.5±1.2 h/night (p=0.022). In LS group, 83.3% patients had 95th percentile pressure >11 cmH2O, although only 7.7% required to change maximum pressure setting beyond 12 cmH2O.  Conclusions: Both pressure ranges appear to be equally effective to correct AHI and improve symptoms. However patients with high span APAP were less compliant to treatment, raising issues about the tolerability of wide pressure range settings of these devices.
Loss of Epithelial Membrane Protein 2 Aggravates Podocyte Injury via Upregulation of Caveolin-1
Authors: Xiaoyang Wan, Zhaohong Chen, Won-Il Choi, Heon Yung Gee, Friedhelm Hildebrandt, Weibin Zhou
Journal: Journal of the American Society of Nephrology (2015)

Nephrotic syndrome is a CKD defined by proteinuria with subsequent hypoalbuminemia, hyperlipidemia, and edema caused by impaired renal glomerular filtration barrier function. We previously identified mutations in epithelial membrane protein 2 (EMP2) as a monogenic cause of this disease. Here, we generated an emp2-knockout zebrafish model using transcription activator-like effector nuclease–based genome editing. We found that loss of emp2 in zebrafish upregulated caveolin-1 (cav1), a major component of caveolae, in embryos and adult mesonephric glomeruli and exacerbated podocyte injury. This phenotype was partially rescued by glucocorticoids. Furthermore, overexpression of cav1 in zebrafish podocytes was sufficient to induce the same phenotype observed in emp2 homozygous mutants, which was also treatable with glucocorticoids. Similarly, knockdown of EMP2 in cultured human podocytes resulted in increased CAV1 expression and decreased podocyte survival in the presence of puromycin aminonucleoside, whereas glucocorticoid treatment ameliorated this phenotype. Taken together, we have established excessive CAV1 as a mediator of the predisposition to podocyte injury because of loss of EMP2, suggesting CAV1 could be a novel therapeutic target in nephrotic syndrome and podocyte injury.
Ventilatory inefficiency relative to oxygen uptake and carbon dioxide output are independent predictors of mortality in pulmonary arterial hypertension
Authors: Maria Clara N. Alencar, Roberta Pulchieri Ramos, Eloara V.M. Ferreira, Flávio Ferlin Arbex, Luiz Eduardo Nery, Jaquelina S. Ota Arakaki, J. Alberto Neder
Journal: European Respiratory Journal (2013)

Background: Exercise intolerance is a well-established prognostic marker in a number of cardiopulmonary diseases. In pulmonary arterial hypertension (PAH), excessive ventilatory (VE) response relative to metabolic demand associated with insufficient O2 delivery are important factors impairing patients' exercise capacity. We therefore investigated whether the dynamic relationship between VE and both pulmonary carbon dioxide output (VCO2) and O2 uptake (VO2) would constitute negative prognostic markers in this patient population. Methods: Eighty-one patients (36 idiopathic and 45 with associated conditions) were followed-up for up to 5 yrs. VE/VCO2 slope (rest-to-peak data) and VO2 efficiency slope (OUES) were calculated and analyzed in association with traditional cardiopulmonary exercise test (CPET)-based measurements. Results: Fourteen patients (17 %) died during the follow-up period. Resting variables were not related to prognosis ( p >0.05). Univariate analysis indicated that peak VO2, ΔVO2/Δ work rate, ΔV’E/ΔV’CO2 and OUES were associated with lower survival ( p <0.05). A multiple regression analysis of dichotomized data obtained after a ROC curve analysis showed that ΔV’E/ΔV’CO2 ≥ 55 [hazard ratio (HR) (95% CI)= 11.16 (1.4-86.6); p = 0.02] and OUES ≤ 0.56 [HR 11.24 (3.5-35.8); p = 0.02] were independent predictors of mortality. Association of these findings increased OR for mortality to 18.2 (5.8-57.3), p <0.01. Conclusion: Ventilatory inefficiency relative to pulmonary gas exchange during rapidly-incremental CPET is a marker of poor prognosis in patients with PAH.
Studies of EN-1639A (Naltrexone): A New Narcotic Antagonist
Authors: RICHARD B. RESNICK, JAN VOLAVKA, ALFRED M. FREEDMAN, MURIEL THOMAS
Journal: American Journal of Psychiatry (1974)

The narcotic antagonist EN-1639A (naltrexone) was studied in 37 heroin addicts and found to be clinically useful, with a low incidence of side effects, lack of toxicity, high degree of acceptability to the patient, and capacity to antagonize the euphoric effects of heroin for up to 72 hours after a single oral dose. These findings provide a basis for expanding studies of the clinical efficacy of naltrexone in the treatment of opiate dependence.
CD30 (Ki-1)-positive anaplastic large-cell lymphomas in 13 patients with and 27 patients without human immunodeficiency virus infection: the first comparative clinicopathologic study from a single institution that also includes 80 patients with other human immunodeficiency virus-related systemic lymphomas.
Authors: U Tirelli, E Vaccher, V Zagonel, R Talamini, D Bernardi, M Tavio, A Gloghini, M C Merola, S Monfardini, A Carbone
Journal: Journal of Clinical Oncology (1995)

PURPOSE CD30 (Ki-1)-positive anaplastic large-cell lymphoma (Ki-1 ALCL) rarely has been described in patients with human immunodeficiency virus (HIV) infection. The purpose of this study was to characterize further the clinicopathologic features of Ki-1 ALCL in patients with HIV infection and, for the first time, to make a comparison with Ki-1 ALCL in patients without HIV infection. PATIENTS AND METHODS From September 1987 to April 1993, 93 patients with HIV infection and systemic non-Hodgkin's lymphoma (NHL) were treated at the Cancer Center of Aviano, Italy; in 13 (14%), the diagnosis was of Ki-1 ALCL subtype. This group of patients was compared with the remaining 80 patients who had other HIV-related NHL and with another group of 27 patients with Ki-1 ALCL who were without a diagnosis of HIV infection. RESULTS There was no case of a T-cell phenotype in the 13 HIV-positive Ki-1 ALCL patients, whereas there was such a phenotype in six of 27 (22%) HIV-negative Ki-1 ALCL patients. In regard to the general characteristics of the two groups with Ki-1 ALCL, more patients with stage IV, two or more extranodal sites at presentation, treatment-related leukopenia, and opportunistic infections as the cause of death were observed in the HIV-positive Ki-1 ALCL group. When these variables were compared with those of the other HIV-related NHL group, such differences were not present. CONCLUSION Ki-1 ALCL is not a rare clinicopathologic entity among NHL in patients with HIV infection. The differences observed within the two Ki-1 ALCL groups of patients may be because of factors related to the HIV infection alone.
Inhaled steroids modify bronchial responses to hyperosmolar saline
Authors: LT Rodwell, SD Anderson, JP Seale
Journal: European Respiratory Journal (1992)

We investigated the effects of inhaled beclomethasone dipropionate (BDP) on airway sensitivity (provocative dose producing a 20% fall in forced expiratory volume in one second (FEV1) from baseline (PD20)) and reactivity (slope of the dose-response curve) to inhaled aerosols of hyperosmolar (4.5%) saline, and histamine or methacholine. This was an open study on 13 patients referred to the laboratory by their respiratory physician for investigation of their asthma. These challenges were performed on separate days before (initial visit) and 8.8 +/- 0.8 (SD) weeks (range 5.6-12.4 weeks) after (visit 1) a treatment period with BDP (dose range 600-1,500 micrograms.day-1). At visit 1 there was a significant reduction in sensitivity to 4.5% NaCl and histamine/methacholine and in reactivity. The PD20 increased 5.6 fold for 4.5% NaCl and 4.1 fold for histamine/methacholine. All patients remained responsive to histamine/methacholine and a fall in FEV1 &gt; 20% to 4.5% saline was documented in 10 of the 13 patients. We conclude that treatment with BDP reduces sensitivity and reactivity to both osmotic and pharmacological challenge.
Stepping determines greater oxygen desaturation than cycling in patients with COPD
Authors: Simone Dal Corso, Carla Malaguti, Anderson Alves de Camargo, Anderson Jose, Luiz Eduardo Nery
Journal: European Respiratory Journal (2011)

Background: It has been shown that walking is more sensitive to detect exercise-induced desaturation than cycling in patients with COPD. However, it is unknown whether the same phenomenon occurs between stepping and cycling.

Objective: To compare exercise-induced desaturation and metabolic and ventilatory adaptations during stepping and cycling.

Methods: Twenty-one patients with COPD (FEV1: 47±13% predicted) underwent, on different days, the maximal cardiopulmonary exercise testing (CPET) and incremental step test (IST) performed on a cycle ergometer and a 20-cm bench, respectively. During CEPT, the work rate (WR) was continuously increased (5–15 W.min-1). IST started with 10 steps/minute and increments of one step every 30 seconds until the tolerance limit. Pulse oximetric saturation (SpO2) was recorded every minute in both tests and desaturation was considered a fall ≥ 4% from resting SpO2.

Results: IST induced a higher desaturation compared to CEPT (-6±4.5% vs -3±3%). Seven patients presented desaturation at IST but not at CPET while two patients showed the opposite. Desaturation in both tests and non desaturation in either tests were observed in five and seven patients, respectively. Among the metabolic and ventilatory variables measured at peak exercise, higher oxygen uptake and lower ventilatory equivalent for oxygen were observed for IST as compared with CEPT (1.3±0.4 L/min vs 1.2±0.4 L/min and 33.5±7.4 vs 36.3±7.8; P < 0.05).

Conclusion: The desaturation was detected only during IST in 33% of patients. VO2 peak is higher, ventilatory demand is lower and desaturation more pronounced during stepping than cycling.
Peptidoglycans Extracted From Gram-Positive Bacteria: Expression of Antitumor Activity According to Peptide Structure and Route of Injection&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: A F Goguel, G Lespinats, C Nauciel
Journal: JNCI Journal of the National Cancer Institute (1982)

The antitumor effect of peptidoglycans of various structures extracted from different gram-positive bacteria was studied, on chemically induced fibrosarcomas, in C3H/He, C57BL/6, and (C57BL/6 X C3H/He)F1 mice. When given sc admixed with tumor cells, only some peptidoglycans (those extracted from Bacillus megaterium and Staphylococcus aureus) enhanced tumor resistance in syngeneic and semiallogeneic hosts, whereas other peptidoglycans (those extracted from Micrococcus lysodeikticus and Corynebacterium poinsettiae) possessed no antitumor effect. When tumor cells were given ip, administration of peptidoglycans by the same route was either without effect on tumor growth or it induced tumor enhancement. Enhancement could be observed with all of the peptidoglycans tested. The antitumor effect when given sc and the ability to stimulate the proliferation of B-lymphocytes were shared by the same two peptidoglycans, while the other two peptidoglycans were devoid of both activities. It appears that these biological activities depend on the structure of the peptide moiety of peptidoglycans and that mitogenic and antitumor responses are stimulated by similar structures.
Impact on survival of surgically defined favorable responses to salvage intraperitoneal chemotherapy in small-volume residual ovarian cancer.
Authors: M Markman, B Reichman, T Hakes, J L Lewis, W Jones, S Rubin, R Barakat, J Curtin, L Almadrones, W Hoskins
Journal: Journal of Clinical Oncology (1992)

PURPOSE To evaluate the impact on survival of the attainment of surgically defined favorable responses (S-R) to salvage intraperitoneal (IP) chemotherapy after initial systemic cytotoxic drug delivery. PATIENTS AND METHODS We examined the survival of patients who were treated on one of three phase II IP trials that were conducted at the Memorial Sloan-Kettering Cancer Center. A total of 58 patients whose largest residual tumor masses measured less than or equal to 0.5 cm in maximum diameter at the initiation of this salvage therapy were assessable for response, 28 of whom (48%) demonstrated a S-R, which included 19 (33%) who achieved a surgically defined complete response (S-CR). RESULTS With a median follow-up of 43+ months (range, 33+ to 58+ months) from the initiation of IP therapy, 12 of 19 (63%) have recurred. The median duration of S-CR for the 10 patients with microscopic residual disease was 32 months compared with 15 months for the nine patients with macroscopic residual disease (largest tumor mass less than or equal to 0.5 cm; P greater than .1). For patients with microscopic residual disease who experienced a S-CR (n = 10) after salvage IP therapy, the median overall survival from the initiation of therapy has not been reached, but will exceed 4 years compared with a 25-month median survival for the nonresponding patients (n = 13; P = .004). The median survival for the 18 patients with small-volume macroscopic disease who responded to therapy was 40 months compared with 19 months for the nonresponders (P = .009). CONCLUSION Although the results of this evaluation are encouraging and suggest that the attainment of a S-R, particularly a S-CR, after IP chemotherapy may result in a clinically meaningful favorable impact on survival, a randomized controlled trial will be required to address definitively this important issue.
Inhibition of phosphodiesterase 4B enhances glucocorticoid-dependent gene transcription in human airway epithelial cells: Implications for the treatment of COPD
Authors: Pawan Sharma, Sylvia Wilson, Robert Newton, Mark Giembycz
Journal: European Respiratory Journal (2013)

Clinical trials involving severe COPD patients showed that PDE4 inhibitor, roflumilast (ROF) reduced exacerbations in patients taking inhaled corticosteroids (ICS) concomitantly. We hypothesised that this clinical benefit is due, in part, to the ability of ROF to  augment  the ability of glucocorticoids to induce anti-inflammatory genes. Using a glucocorticoid response element (GRE) luciferase reporter stably transfected into human airway epithelial cells, fluticasone propionate (FP) induced GRE-dependent transcription in a concentration-dependent manner. However, concurrent addition of ROF with FP enhanced transcription above that produced by FP alone. Similarly, silencing  PDE4B , one of the four PDE4 isogenes, also augmented FP-induced transcription above that produced by FP alone whereas silencing  PDE4A ,  PDE4C  &  PDE4D  was ineffective. Selective PDE4B inhibitor augmented FP-induced transcription in a concentration-dependent manner where a selective PDE4D inhibitor had no effect. We have shown that the β2-adrenoceptor agonist, formoterol, enhanced GRE-dependent transcription. In presence of low concentrations of PDE4B inhibitor, formoterol concentration-response curve was displaced to the left indicating that cells had become more sensitive to β2-adrenoceptor agonist-induced-GRE-dependent transcription whereas the PDE4D inhibitor was inactive. Our data support the tenet that an ICS and PDE4 inhibitor in combination imparts clinical benefit in COPD beyond that provided by an ICS alone. Our data also suggest that inhibition of PDE4B is a primary target that mediates the anti-inflammatory effect of PDE4 inhibitors like ROF.
Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study.
Authors: J Pullen, J Boyett, J Shuster, W Crist, V Land, L Frankel, R Iyer, L Backstrom, J van Eys, M Harris
Journal: Journal of Clinical Oncology (1993)

PURPOSE The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis. PATIENTS AND METHODS With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype. RESULTS The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P &lt; .001 overall). The difference is statistically significant for good-risk patients (P &lt; .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome. CONCLUSION TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.