tbuckley/cabot-search huggingface dataset:
Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment.
Authors: E J Shpall, R B Jones, S I Bearman, W A Franklin, P G Archer, T Curiel, M Bitter, H N Claman, S M Stemmer, M Purdy
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate the capacity of enriched CD34-positive (CD34+) progenitor cells to reconstitute hematopoiesis in poor-prognosis breast cancer patients following administration of a high-dose alkylating agent chemotherapy regimen. PATIENTS AND METHODS Forty-four breast cancer patients received high-dose chemotherapy followed by autologous bone marrow support (ABMS) with CD34+ hematopoietic progenitor cells in five sequentially treated cohorts. Following infusion of CD34+ marrow, cohort no. 1 received no growth factor, cohort no. 2 received granulocyte colony-stimulating factor (G-CSF), and cohort no. 3 received granulocyte-macrophage colony-stimulating factor (GM-CSF). Cohort no. 4 received the CD34+ fractions of both marrow and peripheral-blood progenitor cells (PBPCs) plus G-CSF. Cohort no. 5 received only the CD34+ PBPCs plus G-CSF. Immunohistochemical staining for breast cancer was performed on all hematopoietic cell products before and after the positive selection procedure, to assess quantitatively the level of tumor-cell contamination. RESULTS Cohorts no. 1, 2, 3, 4, and 5 achieved a granulocyte count &gt; or = 500 x 10(9)/L in a median of 23, 10, 16, 11, and 11 days, with a platelet count greater than 20,000 x 10(9)/L documented in a median of 22, 23, 32, 12, and 10 days, respectively. The time to granulocyte reconstitution was significantly shorter for patients who received CD34+ PBPCs alone (cohort no. 5), or in combination with CD34+ marrow (cohort no. 4), when compared with those who received only the CD34+ marrow fraction (P &lt; .01). From 1 to greater than 4 logs of breast cancer cell depletion were documented after CD34-selection, for patients in whom tumor was initially detected. CONCLUSION CD34+ marrow and/or PBPCs provide reliable and timely hematopoietic reconstitution in breast cancer patients receiving high-dose chemotherapy. Contamination of both marrow and PBPCs with breast cancer cells was reduced using this positive selection technique.
A potential new therapy for pulmonary hypertension with the use of compound 21, an angiotensin type 2 receptor (AT2R) agonist
Authors: Erin Bruce, Vinayak Shenoy, Anandharajan Rathinasabapathy, U. Muscha Steckelings, Thomas Unger, Colin Sumners, Mohan K. Raizada, Michael J. Katovich
Journal: European Respiratory Journal (2012)

Pulmonary hypertension (PH) is a debilitating, chronic lung disease that often leads to right-heart failure and death. Currently available therapies are ineffective in significantly improving the quality of life and reducing mortality rates, thereby necessitating the discovery of novel therapeutic interventions. The renin-angiotensin system (RAS) has been associated with the pathophysiology of PH, via increased activity of the deleterious ACE/ANGII/AT1R axis. It has been suggested that AT2R are upregulated in response to cardiovascular injury, and subsequent stimulation of this receptor may oppose the deleterious actions of the RAS axis. However, the role of AT2R in PH has yet to be investigated. We propose that non-peptide AT2R agonist, Compound-21 (C21), will attenuate the progression of monocrotaline (MCT)-induced PH in 8-week-old Sprague Dawley rats. Four weeks post a subcutaneous injection of MCT (50mg/Kg), the rats displayed marked elevation in right ventricular systolic pressure (RVSP, Control: 31.5±0.78; MCT: 82.2±4.52mmHg; p
KPC-2 and OXA-48 carbapenemase-harbouring Enterobacteriaceae detected in an Austrian wastewater treatment plant
Authors: H. Galler, G. Feierl, C. Petternel, F.F. Reinthaler, D. Haas, A.J. Grisold, J. Luxner, G. Zarfel
Journal: Clinical Microbiology and Infection (2013)
Arterial stiffness and endothelial dysfunction in stable COPD patients
Authors: Marina Makarova, Sergey Avdeev, Alexander Chuchalin
Journal: European Respiratory Journal (2012)

Cardiovascular disease is common in COPD patients and is associated with poorer prognosis. Arterial stiffness (AS) is a validated measure of cardiovascular risk.  Aim: To assess AS and endothelial dysfunction (ED) in COPD patients, to determine thier association with other clinical and cardiopulmonary functional parameters.  Methods: We enrolled 41 COPD patients (64.5±7.6 yrs, FEV1 37.7±14.1%) and 34 normal control subjects (CS). Lung function, blood gases, six-minute walking distance (6MWD), nocturnal pulseoximetry, serum C-reactive protein (CRP) were measured. Assessment of AS was performed by use of digital photoplethysmography (Pulse Trace PCA 2 Micro Medical). Change in reflection index (RI) of the digital volume pulse in response to salbutamol (RISALB) and serum endotelin-1 (ET-1) were used to assess ED.  Results: In COPD patients stiffness index (SI) was higher than in CS: 11.3±3.3 vs 6.9±0.9 m/s, p 0,05. The ET-1 levels were elevated in COPD patients and correlated with RISALB (r=-0.46, p=0.03). RISALB was significantly associated with mean nocturnal SpO2 (r=0.38), DLCO (r=0.45).  Conclusion: AS and ED are significantly impaired in COPD patients. Decreased FEV1, 6MWD and systemic inflammation were associated with ED. Hypoxemia, elevated ET-1 level and decreased DLCO have an association with both AS and ED.
Bioavailability of Digoxin Tablets
Authors: John Lindenbaum
Journal: Pharmacological Reviews (1973)

Digoxin tablets are incompletely absorbed by human subjects. Substantial differences in the bioavailability of currently marketed digoxin products have been demonstrated repeatedly. Differing pharmacokinetic patterns have been observed with various preparations. The variation in absorption is not due to lack of tablet content uniformity. Therapeutic ineffectiveness has been noted with products of inferior bioavailability. Establishment of bioavailability standards, and governmental regulation of the problem, are urgently needed. A digoxin preparation that was 100% absorbed would not necessarily be ideal. Urinary digoxin excretion 24-hr after a single dose may prove to be a useful screening test for bioavailability. The cause of variation in the absorption of digoxin tablets remains to be established, but differences in the rate at which such tablets dissolve may be important.
Relative contribution of cytological specimen type in the determination of lung cancer histologic identity – Analysis of one year's comparative data
Authors: Stylianos Michaelides, Aphrodite Emmanouelidou, George Goulas, Ageliki Lazaratou, Despina Melemeni, Aikaterini Blana, Vassilios Handrinos
Journal: European Respiratory Journal (2011)

We retrospectively evaluated the relative contribution of cytological specimens in identifying the histologic type of lung cancer. Seventy-four patients (50 male & 24 female) aged 63±8.9 years (mean±SD), eventually diagnosed to have lung cancer were studied. Diagnosis was established by either bronchoscopic or surgical biopsy.The spectrum of cytological specimens included: simple sputum smear (SP), bronchial washings (BW), post-bronchoscopy sputum (PB), brushing smears (BS) and transthoracic fine needle aspirates (FNA). The distribution of histologic types was as follows: Small Cell Lung Cancer (SCLC) 24 pts (32.4%), Squamous Cell Carcinoma 20 pts. (27%), Adenocarcinoma 14 pts. (18.9%), Undifferentiated Carcinoma 6pts (12.3%), Large cell Carcinoma 2 pts. (0.28%). Analysis of data showed that simple sputum cytology was diagnostic in 24.3% (relative contribution 66.6% for SCLC and 33.4% for NSCLC). Success rate of BW was 42% (almost equally partioned between SCLC & NSCLC 52% & 48% respectively). BS diagnosed 23% of lung cancer, of which 56.3% was the yield for adenocarcinoma. The contribution of FNA smears cannot be evaluated due to the very small sample size (only 2 patients which was successful in both).The overall contribution of cytology in the diagnosis among all types of lung cancer cases studied was 57 pts among a total of 74 (77%). We conclude that simple sputum cytology should not be neglected (having a diagnostic rate of 25% of patients) while the significance of BS in adenocarcinoma (56.3%) should be emphasized given its frequent peripheral location that does not allow obtaining tissue for histologic diagnosis.
Anti-epidermal growth factor (EGFR) antibody, cetuximab, in patients with stage IV colorectal carcinoma who failed all standard therapy: Final report of an access protocol
Authors: G. Spitzer, I. Zackon, P. Stella, L. Zehngebot, C. Henderson
Journal: Journal of Clinical Oncology (2005)

3646 Background: Irinotecan, oxaliplatin, and fluoropyrimidine based regimens have been the mainstay of therapy for metastatic colorectal cancer (mCRC) and options are limited in patients who fail the standard regimens. Final data from a previously reported access study with single agent cetuximab for mCRC patients failing all standard therapy (Zehngebot et al, abstract 3753, ASCO 2004) is now available. Methods: Safety was evaluated in patients with EGFR detectable mCRC and an ECOG PS of ≤ 2. Patients must have exhausted all standard therapies and received at least two chemotherapy regimens for metastatic disease or adjuvant therapy plus one chemotherapy regimen for metastatic disease if the patient progressed within 6 months of completing adjuvant therapy. Patients received an initial cetuximab dose of 400 mg/m2 on Day 1 followed by 250 mg/m2 weekly until disease progression or unacceptable toxicity. Results: : A total of 743 patients were enrolled in the study in approximately 30 sites across the country. The median age was 60 years (range 26–90), 35.9% of pts were ≥ 65 yrs, and 56.1% were male. The median duration of disease from the time of initial diagnosis to study entry was 30 months. The median number of infusions was 11 (range 1–56) and the median duration of therapy was 11.4 weeks (range 1–56), with 11.7% of patients continuing on therapy beyond six months. 44% of the patients experienced no cetuximab delay. Reasons for discontinuation included: progressive disease (61.6%); clinical deterioration (8.0%), patient request (6.9%), death (5.6%), toxicity (2.8%), and other (10.3%). The most commonly reported adverse event was rash 69% (5.5% grade 3/4). Grade 3/4 events included asthenia/malaise (7.9%), fatigue (5.8%), dyspnea (3.8%), nausea/vomiting (3.4%), dehydration (3.4%), and infusion reactions (2.4%). Conclusions: This study identified no unexpected toxicities related to single agent cetuximab and showed cetuximab to be an option for this pretreated population with mCRC who had exhausted all standard therapies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb ImClone Bristol-Myers Squibb
Is controlled oxygen therapy in COPD patients presenting in acute respiratory failure sub-optimal prior to commencement of NIV?
Authors: Shamir Karmali, Thida Win
Journal: European Respiratory Journal (2012)

Introduction: 

Controlled oxygen delivery with target oxygen saturations is a key aim in managing COPD patients in respiratory failure.

Aims: 

This audit assessed if controlled oxygen therapy is utilised on these patients on admission to hospital and prior to NIV in line with British Thoracic Society guidance.

Methods: 

In a district general hospital, case notes for twenty patients with COPD requiring NIV between April 2011 - February 2012 were analysed retrospectively.

FIO2, SpO2 and arterial blood gas values (pH, PaO2, PaCO2 and HCO3) were analysed on admission and prior to commencing NIV (if not started immediately on admission). SpO2 >94% and/or PaO2 >9 kPa were used to indicate 'relative overoxygenation'.

HCO3 > 26 mmol/L on admission was taken to suggest chronic hypercapnia and risk of oxygen sensitivity.

Results: 

65% of patients were admitted with 'relative overoxygenation' (figure 1) of which 54% were immediately started on NIV. However in 46% of patients not immediately started on NIV, over 80% had attempted reduction in oxygenation.

85% of patients had elevated bicarbonate on admission.

![Figure][1] 



Conclusion 

This audit found 'relative overoxygenation' in the majority of our patients on admission to hospital with some correction prior to NIV. Efforts to limit initial overoxygenation may reduce need for NIV in some patients and should be reinforced to first responders.

 [1]: pending:yes
In vivo imaging and tracking of host–microbiota interactions via metabolic labeling of gut anaerobic bacteria
Authors: Naama Geva-Zatorsky, David Alvarez, Jason E Hudak, Nicola C Reading, Deniz Erturk-Hasdemir, Suryasarathi Dasgupta, Ulrich H von Andrian, Dennis L Kasper
Journal: Nature Medicine (2015)
A severity-of-illness score for tuberculosis in the intensive care unit
Authors: Coenraad Koegelenberg, Cecile Balkema, Ynishia Jooste, Jantjie Taljaard, Elvis Irusen
Journal: European Respiratory Journal (2014)

Background: There is a paucity of data on the determinants of mortality of tuberculosis (TB) in the intensive care unit (ICU).The aim of this study was to develop a simple severity-of-illness score for the use in patients with TB necessitating ICU admission.  Methods: All patients admitted to the ICU with TB from January 2012 until May 2013 were prospectively enrolled in order to identify potential parameters of poor outcome. Disease severity, co-morbid diagnoses, clinical features, radiological and laboratory investigations and outcomes were recorded. In addition, we performed an extensive literature review in order to devise a simple scoring system .   Results: 83 patients (44 HIV-positive) were admitted with pulmonary (n=69) and/or extrapulmonary (n=37) tuberculosis. 39 (44.2%) patients died in the ICU. A CD 4   4  140 µmol/L (male) or >120 µmol/L (female), (3) diffuse parenchymal infiltrates / milliary pattern on x-ray, (4) a P:F ratio   Conclusion: Our scoring system can potentially identify patients at higher risk of mortality. Further prospective studies are indicated to validate its use.
Use of immune cell function assay in immune surveillance of lung transplant recipients: Correlations with clinical outcome and other immune assays
Authors: Francesco Bini, Annamaria Grasso, Simona Miserere, Rita Di Domenica, Monica Morosini, Tiberio Oggionni, Manuela Cova, Luisetti Maurizio, Federica Meloni
Journal: European Respiratory Journal (2012)

Introduction : Infection still remains a significant cause of morbidity after lung transplantation. The Cylex ImmuKnow assay (IKA), provides a global assessment of CD4 T cell immune function to help monitor the immune reactive capacity of graft recipients. We use IKA in the immunological follow-up of lung recipients. We assess clinical utility of IKA and correlate its results with other immunological parameters.   Methods : IKA was always performed on clinical demand. From October 2008 to February 2012 we performed IKA on 110 samples. The values of CD4+ T cell activation were classified as strong (> than 525ng/mL of ATP), moderate (525 225) and low ( high CD127 -/dim cells in blood and BAL.   Results : High correlation between lower values and the occurrence of infectious episodes was observed (p  Instead, no correlation was found with the biopsy confirmed diagnosis of acute rejection.  Values of IKA did not correlate with levels of tacrolimus (P=0,8).  Similarly, only a trend toward an inverse relationship was present with CD4+ cell counts.  As for Treg cells counts, again no significant correlation was present.  Of note in 81% of low IKA results, the test was the basis of a change in the immunosuppressive regimen.   Conclusion : IKA values are helpful in identifying patients at high infectious risk and can be used to adapt IS regimen to patient need.
Prevention of gram-positive infections after bone marrow transplantation by systemic vancomycin: a prospective, randomized trial.
Authors: M Attal, D Schlaifer, H Rubie, F Huguet, J P Charlet, E Bloom, J Lemozy, P Massip, J Pris, G Laurent
Journal: Journal of Clinical Oncology (1991)

Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.
Immediate and long-term outcome of left-sided infective endocarditis. A 12-year prospective study from a contemporary cohort in a referral hospital
Authors: N. Fernandez-Hidalgo, B. Almirante, P. Tornos, M.T. González-Alujas, A.M. Planes, M. Galiñanes, A. Pahissa
Journal: Clinical Microbiology and Infection (2012)

The aim of this study was to describe the immediate and long-term prognosis of a contemporary cohort of patients with left-sided infective endocarditis (LSIE). A prospective observational cohort study was conducted in a referral centre. Between January 2000 and December 2011, all consecutive adult patients with LSIE were followed-up until death, relapse, recurrence, need for late surgery, or last control. During the active phase of IE, 174 of 438 patients underwent surgery (40% overall; 43% native valve (NVIE), 30% prosthetic valve (PVIE)) and 125 died (29% overall; 26% NVIE, 39% PVIE). The median follow-up in survivors was 3.2 years (interquartile range (IQR) 1.0-6.0 years). Relapses occurred in seven patients (2.2%; 95% CI, 1.1-4.5) and recurrences in eight (2.6%; 95% CI, 1.3-5.0), with an incidence density of 0.0067 per patient-year (95% CI, 0.0029-0.0133) and high mortality (75% of recurrences). Only four of 130 survivors (3.1%; 95% CI, 1.2-7.6) who were treated surgically during the active phase of the disease, and 14/183 (7.7%; 95% CI, 4.6-12.4) of those not undergoing surgery needed operation during follow-up (p 0.09). In the 313 survivors, actuarial survival was 86% at 1 year (87% NVIE, 83% PVIE), 79% at 2 years (81% NVIE, 72% PVIE) and 68% at 5 years (71% NVIE, 57% PVIE). At 1 year, 115 of 397 patients (29.0%; 95% CI, 24.7-33.6) remained alive, with no surgery requirement, relapse or recurrence. LSIE is associated with considerable in-hospital and long-term mortality, especially PVIE. However, relapses, recurrences and the need for late surgery are uncommon.
Tumors of the Respiratory System Induced in the Common European Hamster by &lt;italic&gt;N&lt;/italic&gt;-Diethylnitrosamine&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Ulrich Mohr, Jurgen Althoff, Norbert Page
Journal: JNCI Journal of the National Cancer Institute (1972)

Male common European hamsters, captured from the wild, were subcutaneously treated once weekly for life with N-diethylnitrosamine at a dose of 20 mg/kg body weight. All animals developed tumors in the respiratory system, with the main target organ being the nasal cavities. Squamous cell papillomas were also seen in the larynx, trachea, and stem bronchi. Two bronchogenic squamous cell carcinomas were found in the animals surviving the longest time after the beginning of treatment.
Activity of imipenem against VIM-1 metallo-β-lactamase-producing Klebsiella pneumoniae in the murine thigh infection model
Authors: G.L. Daikos, A. Panagiotakopoulou, E. Tzelepi, A. Loli, L.S. Tzouvelekis, V. Miriagou
Journal: Clinical Microbiology and Infection (2006)
Longitudinal Study of Cognitive Function in First-Episode and Recent-Onset Schizophrenia
Authors: Sherri Gold, Stephan Arndt, Peg Nopoulos, Daniel S. O’Leary, Nancy C. Andreasen
Journal: American Journal of Psychiatry (1999)

Whether cognitive function in schizophrenia deteriorates, improves, or remains stable is a crucial question. Few studies have examined the longitudinal stability of cognitive function and the relationship between cognitive performance and clinical symptoms over time in a cohort of well-treated patients with schizophrenia.In the present study, 54 patients with first-episode and recent-onset schizophrenia completed a comprehensive cognitive test battery and were rated on symptom measures at index hospitalization and again after 5 years.Performance IQ and full-scale IQ significantly improved, whereas verbal IQ did not change. Group performance improved on some of the neuropsychological tests, including the Circle A letter-cancellation task, free recall of logical memory test score, and the Wisconsin Card Sorting Test. Mean finger-tapping performance worsened over time, whereas performance on other neuropsychological tests did not change. Negative, psychotic, and disorganized symptoms significantly improved over the time period. Changes in negative symptoms were correlated with performance changes in verbal IQ and full-scale IQ but not performance IQ. Improvement in verbal cognition was observed when negative symptoms improved. Psychotic and disorganized symptom dimensions were not correlated with any IQ measure.These results indicate that in a cohort of young patients receiving neuroleptic treatment early in their illness, cognitive performance does not deteriorate--and may improve. Only one of the three symptom dimensions--negative--was associated with change in cognitive performance. This study supports the view that negative symptoms are associated with a poor long-term cognitive outcome and may be closely related to the primary cognitive deficit in schizophrenia.
Respiratory variation of the ballistocardiogram during increased respiratory load and voluntary central apnoea
Authors: O Polo, M Tafti, M Hamalainen, K Vaahtoranta, J Alihanka
Journal: European Respiratory Journal (1992)

Heavy snoring is associated with increased respiratory variation of the ballistocardiogram (BCG). The cause for this association is not known. Although the BCG is a sensitive method to measure myocardial performance, the validity of the signal as a marker of snoring-related haemodynamic changes has not been tested. The aim of this study was to investigate whether ballistocardiographic respiratory variation (BRV) correlates with intrathoracic pressure variation (IPV). The BRV and the IPV were measured in five healthy, normal-weight, awake adults during normal breathing, during breath-holding with constant intrathoracic pressure, and during breathing against increased respiratory resistance (high IPV). The BCG was recorded with the static charge-sensitive bed (SCSB) and the intrathoracic pressure with an oesophageal balloon. The mean BRV was significantly lower during central apnoea than during free breathing (8.2 versus 29.4% p less than 0.0001). When breathing against increased respiratory load, the BRV increased in a linear manner as function of the IPV (r = 0.68, p less than 0.01). There was significant interindividual variation in the response. We conclude that changes in the BRV reflect changes in the IPV. Further studies are needed to evaluate whether the BCG could be used as a noninvasive alternative to the oesophageal balloon in monitoring changes of respiratory resistance during heavy snoring.