tbuckley/cabot-search huggingface dataset:
Topotecan Versus Cyclophosphamide, Doxorubicin, and Vincristine for the Treatment of Recurrent Small-Cell Lung Cancer
Authors: Joachim von Pawel, Joan H. Schiller, Frances A. Shepherd, Scott Z. Fields, J.P. Kleisbauer, Nick G. Chrysson, David J. Stewart, Peter I. Clark, Martin C. Palmer, Alain Depierre, James Carmichael, Jacqueline B. Krebs, Graham Ross, Stephen R. Lane, Richard Gralla
Journal: Journal of Clinical Oncology (1999)

Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-cell lung cancer (SCLC) who had relapsed at least 60 days after completion of first-line therapy.Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg) infused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic review.Response rate was 26 of 107 patients (24.3%) treated with topotecan and 19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The proportion of patients who experienced symptom improvement was greater in the topotecan group than in the CAV group for four of eight symptoms evaluated, including dyspnea, anorexia, hoarseness, and fatigue, as well as interference with daily activity (P< or =.043). Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P<.001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P<.001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both regimens.Topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC and resulted in improved control of several symptoms.
Association between plasma haemoglobin A1c (HbA1c) concentration and overnight desaturation in obstructive sleep apnoea (OSA) patients without diabetes
Authors: Robert Plywaczewski, Przemyslaw Bielen, Anna Czyzak-Gradkowska, Monika Targowska, Pawel Sliwinski
Journal: European Respiratory Journal (2013)

OSA is recognized as an risk factor for insulin resistance and diabetes. Plasma HbA1c concentration is an indicator of mean glycaemia over 2-3 month period (increased HbA1c may precede diabetes). We aimed to assess relationships between plasma HbA1c and OSA severity and complications in subjects without diabetes. We studied 455 OSA pts, mean age=56.3±11 years with moderate to severe OSA (AHI=40.5±21.4) and obesity (BMI=33.2±5.9 kg/m2). Normal HbA1c was found in 240 pts (52.75%), increased HbA1c (≥ 6%) was found in 215 pts (47.25%). Comparison of these groups is shown in the table.

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Multiple linear regression analysis confirmed significant correlation between plasma HbA1c and T90 (β=0.25; p=0.03) and Epworth score (β=0.12; p=0.01). Elevated plasma concentration of HbA1c in OSA pts without diabetes was related to some markers of body oxygenation: significantly lower mean overnight saturation, higher T90 and lower daytime PaO2.

Conclusions: Increased plasma HbA1c concentration was very frequent (in about 50%) in a group of moderate to severe OSA pts without diabetes. Overnight desaturation time (T90) was mainly responsible for HbA1c elevation in this group.
Health-related quality of life in emphysema due to alpha-1-antitrypsin deficiency
Authors: Sandra Manca, Esther Rodriguez, Arturo Huerta, Maria Torres, Lázaro Lourdes, Sergio Curi, Pietro Pirina, Marc Miravitlles
Journal: European Respiratory Journal (2013)

Alpha-1-antitrypsin deficiency (AATD) is an autosomic codominant inherited disorder associated to early onset development of emphysema, that results in significant impairment of health-related quality of life (HRQoL).The aim of this study was to assess the quality of life of patients with emphysema-related AATD compared with a group of patients with smoking COPD.  Methods: Observational, cross-sectional study in patients with a severe alpha1-antitrypsin deficiency (phenotype PI*ZZ) and a control group of COPD. All patients completed the mMRC dyspnea scale, the COPD severity score (COPDSS) and the quality of life questionnaires EQ-5D, LCOPD and CAT.  Results: A total of 35 PI*ZZ patients were included (mean age 56.5 yrs (SD=10.6)), 57.1% male and mean FEV1(%)= 48.7% (SD=17.9%), and 61 COPD (70.3 yrs (9.2)), 80.3% men and FEV1(%)= 47% (16.4%). Scores of the severity and HRQoL questionnaires were similar, with a tendency towards worse scores in PI*ZZ for the EQ-5D (VAS) 64.8 (20.2) vs 71.6 (17.1); p=0.08. Correlations of HRQoL scores and FEV1(% predicted) were significant in both groups for COPDSS and LCOPD, but not for CAT and EQ-5D index. Correlations were stronger for AATD patients: r= -0.570, p  Conclusions: The relationship between severity of lung disease and HRQoL, both generic and specific, is stronger in emphysema associated with AATD compared with smokers COPD. The different impact of the disease may be related to the differential characteristics of AATD patients (younger age, lower smoking consumption and less comorbidities).
Respiratory muscle insufficiency in acute respiratory failure of subjects with severe COPD: treatment with intermittent negative pressure ventilation
Authors: A Corrado, G Bruscoli, E De Paola, GF Ciardi-Dupre', A Baccini, M Taddei
Journal: European Respiratory Journal (1990)

Nine subjects with severe chronic obstructive pulmonary disease (COPD) in acute respiratory failure (ARF) and with marked weakness of the respiratory muscles (Group A) underwent intermittent negative pressure ventilation by means of an iron lung (8 h daily for 7 days). Seven subjects with COPD in stabilized chronic respiratory failure (Group B) were studied as controls and submitted to the same medical therapy without ventilator treatment. Functional respiratory tests were performed before and after 7 days of treatment. After ventilatory treatment, Group A showed an increase of maximum inspiratory pressure (PImax), maximum expiratory pressure (PEmax), vital capacity (VC), arterial oxygen tension (PaO2), pH and a decrease of residual volume (RV), total lung capacity of (TLC) and arterial carbon dioxide tension (PaCO2) (all statistically significant). No improvement was ascertained in the functional parameters of Group B. The expiratory muscles seem to play a determining role in ARF. We conclude that the iron lung is a useful therapeutic defence in removing muscular fatigue and in restoring a good level of respiratory compensation of ARF in severe COPD.
Observation cohort study of outcome of patients referred to a UK regional weaning centre
Authors: Thomas Sanctuary, Denise Camilleri, Sam Goodhand, Natalie Grey, Kelly Stewart, Craig Davidson, Nicholas Hart
Journal: European Respiratory Journal (2012)

Data on referral pattern and outcome of weaning failure patients referred to weaning and rehabilitation centres are limited. We evaluated the outcome of patients between 2006 and 2011 from the clinical database. Of 369 patients referred, 298 were accepted and 194 were eventually admitted to the unit. 63 (32.5%) had neuromuscular disease or chest wall deformity (NMD/CWD), 40 (20.6%) were post surgery, 37 (19.1%) has chronic obstructive pulmonary disease (COPD), 7(3.6%) had obstructive sleep apnoea/obesity hypoventilation (OSA/OHS) and 47 (24.3%) had other neurological or spinal conditions (Other). 87(44.9%) were completely weaned from ventilation and 42 (21.7%) were weaned from invasive to non-invasive. Median time from admission to weaning (TTW) was 18 days. 36 (18.6%) remained dependent on tracheostomy ventilation (TV) and 29 (15.0%) died before discharge. This compares with a mortality rate of 25% in the group of patients accepted, but not transferred.

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Weaning outcomes at the LFU





Mortality has decreased by 12% compared to previous data (Pilcher et al Thorax 2005). Mortality is lowest in the NMD and other neurological conditions groups. Complete ventilator independence was most common in the COPD and post surgery groups. The data indicates improved survival and weaning success in the group admitted to the LFU compared to those accepted but not transferred.
Uremic Toxicity of Advanced Glycation End Products in CKD
Authors: Andréa E.M. Stinghen, Ziad A. Massy, Helen Vlassara, Gary E. Striker, Agnès Boullier
Journal: Journal of the American Society of Nephrology (2015)

Advanced glycation end products (AGEs), a heterogeneous group of compounds formed by nonenzymatic glycation reactions between reducing sugars and amino acids, lipids, or DNA, are formed not only in the presence of hyperglycemia, but also in diseases associated with high levels of oxidative stress, such as CKD. In chronic renal failure, higher circulating AGE levels result from increased formation and decreased renal clearance. Interactions between AGEs and their receptors, including advanced glycation end product-specific receptor (RAGE), trigger various intracellular events, such as oxidative stress and inflammation, leading to cardiovascular complications. Although patients with CKD have a higher burden of cardiovascular disease, the relationship between AGEs and cardiovascular disease in patients with CKD is not fully characterized. In this paper, we review the various deleterious effects of AGEs in CKD that lead to cardiovascular complications and the role of these AGEs in diabetic nephropathy. We also discuss potential pharmacologic approaches to circumvent these deleterious effects by reducing exogenous and endogenous sources of AGEs, increasing the breakdown of existing AGEs, or inhibiting AGE-induced inflammation. Finally, we speculate on preventive and therapeutic strategies that focus on the AGE-RAGE axis to prevent vascular complications in patients with CKD.
Improved right ventricular function after substantial afterload reduction in patients with pulmonary arterial hypertension
Authors: Marielle van de Veerdonk, Tim Marcus, Harm-Jan Bogaard, Nico Westerhof, Anton Vonk-Noordegraaf
Journal: European Respiratory Journal (2012)

Introduction

In pulmonary arterial hypertension (PAH), increased load leads to right ventricular (RV) dysfunction. We showed that despite a modest reduction in pulmonary vascular resistance (PVR) after treatment, RV function can decrease resulting in poor prognosis1.

Aims

We hypothesize that RV function can be sustained when therapies reduce RV load to a larger extent. We will compare RV load in PAH patients with improved/stable RV function to patients with decreased RV function during follow-up.

Methods

76 patients underwent right heart catheterization to measure mean pulmonary artery pressure (mPAP) and PVR and MRI to assess RV ejection fraction (RVEF) at baseline and after 1 year of therapy. During a subsequent follow-up of 47months, 17 patients died.

Results

After therapy, 61% of the patients showed an improved/stable RVEF and had a better prognosis than patients with decreased RVEF (p=0.01). Patients with improved/stable RVEF showed a larger reduction in load (ΔmPAP: -9±12mmHg; ΔPVR: -231±301dyne·s·cm-5) than patients with decreased RVEF (ΔmPAP: 3±10mmHg; ΔPVR: 20±313dyne·s·cm-5, both p<0.001). Cardiac output (CO) increased in case of improved/stable RVEF (0.9±2.1L/min) and declined in case of decreased RVEF (0.4±1.8L/min, p=0.01). No differences were observed in 6-min walk distance or NT-proBNP.

Conclusions

PAH patients with sustained RV function showed a substantial load reduction after therapy and had a better prognosis than patients with decreased RV function. This might imply that preserved RV function and improved survival can be achieved if mPAP is substantially reduced, which requires a strong decrease in PVR.

References

1vd Veerdonk et al. JACC 2011.
Low-dose 5-fluorouracil in combination with salicylic acid as a new lesion-directed option to treat topically actinic keratoses: histological and clinical study results
Authors: E. Stockfleth, H. Kerl, T. Zwingers, C. Willers
Journal: British Journal of Dermatology (2011)

Actinic keratoses (AKs) arise after chronic sun exposure. Because long-term ultraviolet (UV) damage may induce proliferation of atypical keratinocytes, treatment of AKs is recommended.To compare 5-fluorouracil 0·5%/salicylic acid 10·0% [low-dose 5-FU/SA (Actikerall®)] with diclofenac 3% in hyaluronic acid (diclofenac HA) and vehicle for the treatment of AKs.This was a randomized, placebo-controlled, double-blind, parallel-group, multicentre trial. Patients received topical low-dose 5-FU/SA once daily, its vehicle or diclofenac HA twice daily for a maximum of 12 weeks. The final evaluation was at week 20. The primary objectives were to demonstrate the histological clearance rate of one predefined lesion. The secondary objectives were the improvement of treated lesions, tolerability and safety.There were 470 patients with 4-10 AK lesions each (grade I or II) on the face/forehead or bald scalp included in the study. Low-dose 5-FU/SA was superior to diclofenac HA (P < 0·01) and vehicle (P < 0·0001) for histological clearance of one representative lesion 8 weeks post-treatment. In 72·0%, 59·1% and 44·8% of patients in the low-dose 5-FU/SA, diclofenac HA and vehicle groups, respectively, the week-20 biopsy revealed no AKs. Significantly more lesions were cleared with low-dose 5-FU/SA (74·5%) compared with diclofenac HA (54·6%; P < 0·001) or vehicle (35·5%; P< 0·001). Low-dose 5-FU/SA was superior in terms of complete clinical clearance: 55·4%, vs. diclofenac HA (32·0%, P < 0·001) and vehicle (15·1%P < 0·001). Application-site disorders (mainly burning and inflammation) were more frequent with low-dose 5-FU/SA but mainly of mild to moderate intensity.Topical low-dose 5-FU/SA demonstrated higher histological and clinical clearance rates vs. diclofenac HA or vehicle. Low-dose 5-FU/SA is an effective lesion-directed treatment for AKs.
Indices from flow-volume curves in relation to cephalometric, ENT- and sleep-O2 saturation variables in snorers with and without obstructive sleep-apnoea
Authors: JM Bogaard, FG van der Meche, RM Poublon, AZ Ginai, PI Schmitz, A Bubberman, AM Slappendel, H Boot
Journal: European Respiratory Journal (1995)

In a group of 37 heavy snorers with obstructive sleep apnoea (OSA, Group 1) and a group of 23 heavy snorers without OSA (Group 2) cephalometric indices, ENT indices related to upper airway collapsibility, and nocturnal O2 desaturation indices were related to variables from maximal expiratory and inspiratory flow-volume (MEFV and MIFV) curves. The cephalometric indices used were the length and diameter of the soft palate (spl and spd), the shortest distance between the mandibular plane and the hyoid bone (mph) and the posterior airway space (pas). Collapsibility of the upper airways was observed at the level of the tongue base and soft palate by fibroscopy during a Müller manoeuvre (mtb and msp) and ranked on a five point scale. Sleep indices measured were the mean number of oxygen desaturations of more than 3% per hour preceded by an apnoea or hypopnoea of more than 10 s (desaturation index), maximal sleep oxygen desaturation, baseline arterial oxygen saturation (Sa,O2) and, in the OSA group, percentage of sleep time with Sa,O2 < 90%. The variables obtained from the flow-volume curves were the forced vital capacity (FVC), forced expiratory and inspiratory volume in 1 s (FEV1 and FIV1), peak expiratory and peak inspiratory flows (PEF and PIF), and maximal flow after expiring 50% of the FVC (MEF50). The mean of the flow-volume variables, influenced by upper airway aperture (PEF, FIV1) was significantly greater than predicted.(ABSTRACT TRUNCATED AT 250 WORDS)
A rapid chemokine response of macrophage inflammatory protein (MIP)-1α, MIP-1β and the regulated on activation, normal T expressed and secreted chemokine is associated with a sustained virological response in the treatment of chronic hepatitis C
Authors: J. Florholmen, M.G. Kristiansen, S.E. Steigen, S.W. Sørbye, E.J. Paulssen, J.M. Kvamme, Z. Konopski, T. Gutteberg, R. Goll
Journal: Clinical Microbiology and Infection (2010)

The role of chemokines in chronic hepatitis C virus (HCV) infection is not fully understood. The present study aimed to characterize the baseline serum concentrations and the initial β-chemokine response to treatment with interferon-α and ribavirin with respect to the final clinical outcome of virological response to treatment. Serum concentrations of alanine aminotransferase (ALT) and of the CC subfamily chemokines [macrophage inflammatory protein (MIP)-1α, MIP-1β, monocyte chemoattractant protein (MCP)-1 and the regulated on activation, normal T expressed and secreted (RANTES) chemokine] were measured in patients with chronic HCV infection and in healthy individuals. Necroinflammation and fibrosis were scored in liver biopsies. Treatment outcomes were classified as with or without a sustained virological response after a full-course treatment according to the genotypes. The main treatment group consisted of 72 patients with chronic hepatitis C, whereas 24-h blood samples were available for 42 patients. Increased baseline levels of all CC chemokines were found in the two responder groups compared to the healthy controls, although significant levels were reached only for MIP-1α and MCP-1. No correlation was observed between chemokine levels and serum ALT levels, any histological necroinflammatory parameters, or the fibrosis grade. After 24 h of treatment, increases in MIP-1α, MIP-1β and RANTES levels were exclusively observed in the group with sustained virological response. MCP-1 was also significantly increased after 24 h in both responder groups, although no differences were observed between the two responder groups. In conclusion, an early MIP-1α, MIP-1β, and RANTES response may predict a sustained response to virological treatment.
Characterization of a Cell Line From Human Transitional Cell Cancer of the Urinary Tract 2
Authors: A. Y. Elliott, P. Cleveland, J. Cervenka, A. E. Castro, Nell Stein, T. R. Hakala, E. E. Fraley
Journal: JNCI Journal of the National Cancer Institute (1974)

A cell line designated 253J was established from a biopsy specimen of retroperitoneal metastasis in a man with multiple transitional cell cancers of the urinary tract. The cells in early and late passages were small and epithelial and had a doubling time of 48 hours. The growth of these cells in culture was characterized by the absence of contact inhibition as evidenced by multilayering. There were virus-like particles in both the original surgical specimen and in cells in culture. The particles were in cytoplasmic vesicles, free in the cytoplasm, or outside both normal and degenerating cells. These particles, varying in size from 30 to 130 nm, had an electron-dense nucleoid and were bounded by a unit membrane. Karyotypic analysis showed the presence of a hyperdiploid stemline with persistent marker chromosomes and chromosomes with multiple rearrangements resulting in unusual G and C banding patterns. The malignant nature of the line was verified by 1) the production of transplantable tumors in immune-depressed hamsters after inoculation with 253J cell suspension and 2) the growth of 253J cells in agar. These cells, in culture over 24 months, have been subcultured over 60 times and continue to retain their epithelial morphology and malignancy.
The role of BLIMP1 in lymphomagenesis
Authors: Junli Yan, Jianming Jiang, Cheng Aeng Lim, Qiang Wu, Patrick Tan, Keh Chuang Chin, Huck Hui Ng
Journal: Clinical Cancer Research (2007)

C75   The discovery of frequent inactivation of  BLIMP1  in activated B cell-like DLBCL  indicates that BLIMP1 has an important role in the pathogenesis  of this lymphoma subtype  , and possibly functions as a tumor suppressor gene. However a recent report shows that the presence of variable percentages of BLIMP1-positive tumor cells in about half of DLBCL cases, and patients with higher BLIMP1 expression are significantly correlated with shorter failure free survival. This raises the possibility that higher BLIMP1 expression could possibly promote the development of lymphoma. Deregulated  BCL-6  expression contributes to lymphomagenesis in part by functional inactivation of p53. We found that BLIMP1 acts in an auto-regulatory feedback loop that controls p53 activity through repression of  p53  transcription.  Our finding that BLIMP1 represses  p53  expression suggests that high expression of BLIMP1 might also promote the development of tumor by suppression of p53 activation. It would be of interest to study the relationship between BLIMP1 and p53 status along with patient survival in DLBCL.
Brittle Diabetes in the Elderly
Authors: Susan J Benbow, Angela Walsh, Geoffrey V Gill
Journal: Journal of the Royal Society of Medicine (2001)

Severely unstable, or brittle, diabetes can be disruptive to patients, carers and diabetes care teams. The peak age-group for brittle diabetes is 15-30, but there are reports of its occurrence in much older patients. To explore the characteristics and cause of brittle instability perceived by diabetologists in elderly patients we circulated a questionnaire to all UK hospital diabetic clinics for adults. 130 (56%) of 231 replied. Reports were obtained on 55 patients fulfilling our criteria for 'elderly brittle diabetes'--namely, age > or =60 years, on insulin treatment, and experiencing life-disrupting glycaemic instability of any kind associated with frequent or long admissions to hospital. Further information was obtained by a research nurse who visited the relevant clinics. The mean age of patients was 74 years (range 60-89) and 71% were female. The brittleness was classed as mixed glycaemic instability in 22 (44%), recurrent ketoacidosis in 16 (29%) and recurrent hypoglycaemia in 15 (27%). In 2 cases there was insufficient information for classification. The diabetes care team judged the brittleness to have multiple origins in two-thirds of the cases: problems with memory or behaviour were rare, and in only 4 cases was deliberate manipulation of therapy considered a possibility. 84% of the patients were living independently. In younger patients the principal manifestation of brittle diabetes is recurrent ketoacidosis. The present survey, though possibly subject to ascertainment bias, indicates that the patterns of instability and their causation may be different in elderly patients. With the growing use of insulin in the elderly, brittle diabetes is likely to be encountered increasingly often in this age-group.
Radiation leukemia in C57BL/6 mice. III. Correlation of altered expression of terminal deoxynucleotidyl transferase to induction of leukemia.
Authors: N H Pazmiño, R McEwan, J N Ihle
Journal: The Journal of Experimental Medicine (1978)

The expression of terminal deoxynucleotidyl transferase (TdT) in the thymus and bone marrow of irradiated mice has been examined. Mice given the leukemogenic regimen of irradiation of four weekly doses of 175 rads starting at 1 mo of age show a long-term elimination of TdT activity in the bone marrow and a reduction of TdT activity in thymocytes. In such mice, the reappearance of normal levels of TdT in the thymus appears to only be associated with the onset of overt leukemia. This effect on TdT expression was shown to be uniquely associated with the leukemogenic regimen of irradiation in that nonleukemogenic irradiation or variations such as bone marrow reconstitution or age which reduce leukemias did not show the same phenotypic effects on TdT expression. The basis for the loss of TdT-positive cells was shown not to be due to the lack of the requisite factors involved in differentiation, but rather to the ability of leukemogenic doses of irradiation to reduce or eliminate an inducible bone marrow stem cell. These results are discussed with respect to the possible mechanisms involved in radiation-induced leukemias in mice.