tbuckley/cabot-search huggingface dataset:
Bronchodilator treatment response mapping in COPD using hyperpolarised gas ventilation MRI
Authors: Felix Horn, Helen Marshall, David Barber, Juan Parra-Robles, David Lipson, Rod Lawson, Jim Wild
Journal: European Respiratory Journal (2013)

Lung imaging using hyperpolarised ³He gas MRI (HP-MRI) [ Wild J., et al., Mag. Reson. in Medicine 2002; 47:687-95] is able to regionally resolve changes in lung ventilation in response to therapy in obstructive airways diseases such as COPD.

A novel way to quantitatively map regional treatment response with ventilation difference mapping of the lungs of patients pre- and post-therapy using HP-MRI was designed and evaluated.

The method was tested with COPD patient datasets. Ventilation images were acquired using HP-MRI; A baseline scan before application of standard prescription bronchodilator and one after. The post treatment datasets were registered [ Barber D.C. et al., Medical image analysis 2007; 11:648-62] to the baseline image and segmented. All datasets were normalised and smoothed. The treatment response map was generated as the difference between baseline and post treatment image.

![Figure][1] 



Figure 1(G) shows the treatment response map of a COPD patient. Green represents increased ventilation post bronchodilator, red areas show a decrease in ventilation. This method enables a direct mapping of ventilation changes pre and post-treatment.

Treatment response mapping provides a novel way to quantify and visualise regional differences in lung ventilation pre- and post-treatment as shown here in a COPD patient dataset.

Funding by EU FP7 Airprom & PInet

GSK Study RES111175 is also acknowledged as a co-sponsor of this research.

 [1]: pending:yes
Oxygen kinetics during 6-minute walk tests using mobile telemetric cardiopulmonary monitoring
Authors: Lukas Kern, Sophie Condrau, Florent Baty, Wiegand Jan, Andrea Azzola, Michael Tamm, Martin Brutsche
Journal: European Respiratory Journal (2011)

Background & aim: Mean response time (MRT) is a prognostic factor for patients with congestive heart failure (CHF). With the current project we sought to validate the assessment of MRT using Mobile Telemetric Cardiopulmonary Monitoring (MOB) during a conventional 6-minute walk test (6MWT).

Material and methods: Oxygen uptake profiles of 203 patients and 16 healthy controls were obtained using MOB (Oxycon Mobile®) during a 6MWT. Curves were fitted using asymptotic regression models. The following parameters were assessed: O2-deficit, baseline and peak O2-uptake, MRT. MOB does not provide information on work load. Therefore, MRT was reparametrized (MRT*=MRT/dVO2) to correct for this variable. Differences in MRT* between disease categories were tested using ANOVA F-test. Associations between MRT* and patient outcome (hospitalisation and/or death) was tested using Cox proportional hazards regression.

Results: O2-deficit and MRT* were significantly increased in patients compared to healthy controls (p<0.001). There was no significant difference between other disease categories. MRT* significantly predicted the patient outcome only in patients with CHF (p=0.004, Figure 1).

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Figure 1





Conclusion: Compared to healthy controls MRT* was prolonged in all patient groups. MRT* was a significant prognostic factor for patients with CHF. We could therefore reproduce previous results obtained with cardiopulmonary exercise testing using MOB during a 6MWT.

 [1]: pending:yes
Assembly and characterization of heterochromatin and euchromatin on human artificial chromosomes.
Authors: Brenda R Grimes, Jennifer Babcock, M Katharine Rudd, Brian Chadwick, Huntington F Willard
Journal: Genome biology (2004)

Human centromere regions are characterized by the presence of alpha-satellite DNA, replication late in S phase and a heterochromatic appearance. Recent models propose that the centromere is organized into conserved chromatin domains in which chromatin containing CenH3 (centromere-specific H3 variant) at the functional centromere (kinetochore) forms within regions of heterochromatin. To address these models, we assayed formation of heterochromatin and euchromatin on de novo human artificial chromosomes containing alpha-satellite DNA. We also examined the relationship between chromatin composition and replication timing of artificial chromosomes.Heterochromatin factors (histone H3 lysine 9 methylation and HP1alpha) were enriched on artificial chromosomes estimated to be larger than 3 Mb in size but depleted on those smaller than 3 Mb. All artificial chromosomes assembled markers of euchromatin (histone H3 lysine 4 methylation), which may partly reflect marker-gene expression. Replication timing studies revealed that the replication timing of artificial chromosomes was heterogeneous. Heterochromatin-depleted artificial chromosomes replicated in early S phase whereas heterochromatin-enriched artificial chromosomes replicated in mid to late S phase.Centromere regions on human artificial chromosomes and host chromosomes have similar amounts of CenH3 but exhibit highly varying degrees of heterochromatin, suggesting that only a small amount of heterochromatin may be required for centromere function. The formation of euchromatin on all artificial chromosomes demonstrates that they can provide a chromosome context suitable for gene expression. The earlier replication of the heterochromatin-depleted artificial chromosomes suggests that replication late in S phase is not a requirement for centromere function.
Abstract P106: Cerebral Health Index as a Measure of Neurological Recovery in an Asphyxial Cardiac Arrest Model
Authors: David L Sherman, Xiaofeng Jia, Nhu-An T Le, Manan Hathi, Nitish V Thakor, Romergryko G Geocadin
Journal: Circulation (2008)

Background Cardiac arrest (CA) can lead to significant neurological damage following resuscitation. A real-time tool for monitoring of neurological status in CA survivors is likely to have a significant impact on post-CPR therapy. To avoid typical subjective prediction of outcome, we have developed a quantitative EEG-based Cerebral Health Index (CHI), a multiparametric algorithm combining several separate spectral, temporal and probabilistic features. CHI is a measure of outcome that evaluates and scores the EEG post-resuscitation from CA. In the present study, we compared CHI to a species-specific behavioral outcome scoring measure, the Neurological Deficit Scores (NDS). Previously calibrated and tested, NDS includes multiple generalized neural, motor, sensory and behavioral subscores. We demonstrated the utility of CHI as a measure of monitoring neurological status as given by NDS. Methods CHI is an empirically trained algorithm that allows for parameter weighting to uniquely characterize the recovering EEG. We investigated the utility of CHI by comparing 72-h CHI values to 72-h of an asphyxial CA rodent model. Sixteen rats underwent a baseline EEG recording followed by 7- or 9-min asphyxia and anesthesia washout which led to CA. The NDS was scored at 72 hr after CA with concurrent 30-min EEG recording. The rats were divided into two groups: 8 rats with known NDS outcomes were used for training the CHI algorithm and 8 rats were used for testing the algorithm in a single blinded fashion. CHI values of the testing group were then compared to their corresponding NDS outcomes via Receiver Operator Characteristic (ROC) curve calculation. Results Physiological measures and arrest times were comparable in both poor and good outcome animals. On a scale basis of 0–80, average CHI values were 70 (±3.8) and 51 (±4.4) for the good and bad outcome animals, respectively. This translated to respective t-test p-values of p≤0.05. ROC analyses on testing cohorts at 72 hr showed an average area under the curve of 0.9. Conclusion CHI is a multi-feature index for accurately describing neurological status after CA in rats. CHI can potentially be used to supplement the traditional neurological exam to make EEG characterization a routine part of post-CA assessments.
Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease
Authors: B von Lampe
Journal: Gut (2000)

<h3>BACKGROUND/AIMS</h3> Alterations in synthesis and breakdown of extracellular matrix components are known to play a crucial role in tissue remodelling during inflammation and wound healing. Degradation of collagens is highly regulated by a cascade of matrix metalloproteinases (MMPs). The current study was therefore designed to determine gene expression patterns of MMPs and their tissue inhibitors (TIMPs) in single endoscopic biopsies of patients with inflammatory bowel disease (IBD). <h3>PATIENTS/METHODS</h3> mRNA expression was measured by quantitative competitive polymerase chain reaction (PCR) in biopsies from patients with ulcerative colitis (n=21) and Crohn9s disease (n=21). Protein expression was analysed by western blotting and immunohistochemistry. <h3>RESULTS</h3> MMP-2, MMP-14, and TIMP-1 mRNAs were marginally increased in inflamed, but 9–12-fold increased in ulcerated colonic mucosa in IBD whereas TIMP-2 mRNA expression remained unchanged. MMP-1 and MMP-3 mRNA expression correlated well with the histological degree of acute inflammation, resulting in more than 15-fold increased MMP-1 and MMP-3 mRNA levels in inflamed versus normal colon samples from patients with ulcerative colitis and Crohn9s disease. <h3>CONCLUSION</h3> Profound overexpression of MMP-1 and MMP-3 mRNA transcripts suggests an important role for these enzymes in the process of tissue remodelling and destruction in inflammatory bowel disease.
Lysosomal hydrolases of the epidermis
Authors: P.D MIER, JOSÉ J.M.A. VAN DEN HURK
Journal: British Journal of Dermatology (1975)

SUMMARY Five distinct ester hydrolases (EC 3.1) have been characterized in guinea-pig epidermis. These are carboxylic esterase, acid phosphatase, pyrophosphatase, and arylsulphatases A and B. Their properties are consistent with those of lysosomal enzymes.
Palmitate transport by rat renal basolateral membrane vesicles in the presence of albumin.
Authors: M E Trimble
Journal: Journal of the American Society of Nephrology (1993)

Long chain fatty acids are an important metabolic fuel for renal proximal tubules. Because of their insolubility, they are carried in the blood primarily bound to albumin. Processes involved in the cellular uptake of albumin-bound ligands are incompletely understood. To determine how fatty acids enter renal tubular cells when substrate was presented primarily bound to albumin (molar ratio albumin:palmitate = 1.0), [3H]palmitate uptake by basolateral membrane vesicles (BLMV) isolated from rat renal cortex was measured by a rapid filtration technique. The pattern of uptake was strikingly affected by buffer composition. In low-ionic-strength buffer (300 mM mannitol, 20 mM Tris-N-hydroxethylpiperazine-N'-2-ethanesulfonic acid [HEPES]), [3H]palmitate uptake plateaued in less than 1 min. The calculated volume of distribution of [3H]palmitate indicated extensive binding. In high-ionic-strength buffer with an inwardly directed NaCl, sodium gluconate, or KCl concentration gradient (100 mM) or equal intravesicular and extravesicular NaCl concentration (100 mM), uptake was biphasic with peak values 1.4- to 3-fold higher than plateau values. To test whether uptake could be specifically inhibited, phloretin (200 microM), probenecid (500 microM), or 4,4'-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS; 500 microM) was added to NaCl uptake buffer. These agents were without effect on initial uptake but inhibited the normal biphasic pattern. The biphasic uptake pattern suggested binding followed by translocation to the interior of BLMV with subsequent mediated efflux. Medicated palmitate efflux was demonstrated in BLMV preloaded with [3H]-palmitate in NaCl buffer by: (1) phloretin inhibition of efflux and (2) trans-stimulation of efflux by p-aminohippurate. Results suggest that the translocation of fatty acids derived from albumin:fatty acid complexes occurs only in the presence of high external ion concentration. Subsequent equilibration of fatty acids between albumin, BLMV, and vesicle interior is mediated by the organic anion transport system.
Immunotoxin therapy of small-cell lung cancer: a phase I study of N901-blocked ricin.
Authors: T J Lynch, J M Lambert, F Coral, J Shefner, P Wen, W A Blattler, A R Collinson, P D Ariniello, G Braman, S Cook, D Esseltine, A Elias, A Skarin, J Ritz
Journal: Journal of Clinical Oncology (1997)

PURPOSE Immunotoxins could improve outcome in small-cell lung cancer (SCLC) by targeting tumor cells that are resistant to chemotherapy and radiation. N901 is a murine monoclonal antibody that binds to the CD56 (neural cell adhesion molecule [NCAM]) antigen found on cells of neuroendocrine origin, including SCLC. N901-bR is an immunoconjugate of N901 antibody with blocked ricin (bR) as the cytotoxic effector moiety. N901-bR has more than 700-fold greater selectivity in vitro for killing the CD56+ SCLC cell line SW-2 than for an antigen-negative lymphoma cell line. Preclinical studies suggested the potential for clinically significant cardiac and neurologic toxicity. We present a phase I study of N901-bR in relapsed SCLC. PATIENTS AND METHODS Twenty-one patients (18 relapsed, three primary refractory) with SCLC were entered onto this study. Successive cohorts of at least three patients were treated at doses from 5 to 40 microg/kg/d for 7 days. The initial three cohorts received the first day's dose (one seventh of planned dose) as a bolus infusion before they began the continuous infusion on the second day to observe acute toxicity and determine bolus pharmacokinetics. Toxicity assessment included nerve-conduction studies (NCS) and radionuclide assessment of left ventricular ejection fraction (LVEF) before and after N901-bR administration to fully assess potential neurologic and cardiac toxicity. RESULTS The dose-limiting toxicity (DLT) of N901-bR given by 7-day continuous infusion is capillary leak syndrome, which occurred in two of three patients at the dose of 40 microg/kg (lean body weight [LBW])/d. Detectable serum drug levels equivalent to effective in vitro drug levels were achieved at the 20-, 30-, and 40-microg/kg(LBW)/d dose levels. Specific binding of the immunotoxin to tumor cells in bone marrow, liver, and lung was observed. Cardiac function remained normal in 15 of 16 patients. No patient developed clinically significant neuropathy. However, a trend was noted for amplitude decline in serial NCS of both sensory and motor neurons. One patient with refractory SCLC achieved a partial response. CONCLUSION N901-bR is an immunotoxin with potential clinical activity in SCLC. N901-bR is well tolerated when given by 7-day continuous infusion at the dose of 30 microg/kg(LBW)/d. Neurologic and cardiac toxicity were acceptable when given to patients with refractory SCLC. A second study to evaluate this agent after induction chemoradiotherapy in both limited- and extensive-stage disease was started following completion of this study.
Respiratory resistance and intrinsic positive end-expiratory pressure (PEEPi) in patients with the adult respiratory distress syndrome (ARDS)
Authors: C Broseghini, R Brandolese, R Poggi, M Bernasconi, E Manzin, A Rossi
Journal: European Respiratory Journal (1988)

Fourteen consecutive ARDS patients were examined within 24 h from the onset of mechanical ventilation to determine respiratory resistance (Rrs) and compliance (Cstrs), and to assess the influence of "intrinsic" positive end-expiratory pressure (PEEPi) on the measurement of Cstrs. Flow, pressure, and changes in lung volume were measured with the transducers of the Servo 900C Siemens ventilator. Airway occlusion was performed with the end-inspiratory and end-expiratory buttons of the ventilator. We found PEEPi (3.0 +/- 2.6 cm H2O) in ten of the fourteen patients. Without the correction for PEEPi, Cstrs was underestimated by 13.9 +/- 10% on average in the group as a whole (fourteen patients), and by 19.5 +/- 5.9% in the ten ARDS patients with PEEPi. Maximum and minimum respiratory resistance (Rrsmax and Rrsmin), and frequency-dependence of Rrs were also measured. On average, there was a marked frequency-dependence of resistance, as manifested by the difference between Rrsmax and Rrsmin, with an increase of both Rrsmin (7.7 +/- 4.2 cm H2O.l-1.s) and Rrsmax (14.3 +/- 5.0 cm H2O.l-1.s). The added resistance of the endotracheal tubes and ventilator tubings was flow dependent, and averaged 13.2 +/- 2.9 cm H2O.l-1.s.(ABSTRACT TRUNCATED AT 250 WORDS)
Report of the working party of the "UEMS Monospeciality Section on Pneumology" on training requirements and facilities in Europe
Authors: JH Dijkman, J Martinez Gonzales del Rio, R Loddenkemkper, K Prowse, N Siafakas
Journal: European Respiratory Journal (1994)

<h3>Introduction</h3> Multiple nutritional risk assessment tools are available, but there are limited data on their application in the acute setting. We explored the validity of two tools in a tertiary Children9s Hospital9s acute unit and the cohort9s nutritional status using WHO definitions. <h3>Methods</h3> Prospective study n=300 (median 38 months; 44.6% female; 25.7% ≤12 months). Participants had standard anthropometry measured, all were screened using the Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP), the Paediatric Malnutrition Screening Tool (PMST) (modified STAMP) and 125 were additionally screened using the Paediatric Yorkhill Malnutrition Screening (PYMS) tool. <h3>Results</h3> The percentages with medium/high nutritional risk were as follows: STAMP 73.1%, PMST 79.3% and PYMS 30%. Height/weight were normally distributed with: 3.4% stunted (height-for-age z-score &lt;−2); aged ≤ 5 years, 6.8% wasted (weight-for-height z-score (WHZ) &lt;−2), 17.9% overweight (WHZ 1–2) and 6.2% obese (WHZ &gt;2); aged &gt;5 years, 5.8% thin (body mass index (BMI)-z-score (BAZ) &lt;−2), 17.3% overweight (BAZ 1–2) and 5.8% obese (BAZ &gt;2). The tools showed poor specificity and variable sensitivities when compared with WHO malnutrition criteria, with positive predictive values of &lt;50%. κ-Analysis also showed poor agreement between the tools and the WHO cut-offs. <h3>Conclusion</h3> These results suggest that nutritional screening tools have poor sensitivity and are difficult to interpret in the acute setting. It may be more effective to include the assessment of weight and height and nutritional intake in the context of the acute presentation as part of routine clinical assessment rather than relying on screening tools to identify those at risk.
Omentoplasty for managing post-surgery complications of aspergilloma in a case of right pulmonary artery agenesis
Authors: Ramona Miron, Cristina Grigorescu, Violeta Cojocariu
Journal: European Respiratory Journal (2011)

Background:  The greater omentum pedicle flap transposition is not an uncommon treatment approach in thoracic surgery. This method is described as the final solution to save patient9s life, after right pneumonectomy with subsequent complications.   Case report:  A 32 years old woman admitted in our clinic in April 2010 for severe dyspnea, hemoptysis was diagnosed with right pulmonary artery agenesis and aspergillum cavity. The patient had a sinuous clinical evolution: in 1999, she presented right infiltrative tuberculosis healed after six months treatment, but in the same year, when investigated again because of persistent lesions revealed on X-ray and CT, she was treated in ambulatory for repeated lower airways infections. On June 2010, the patient suffered a right pneumonectomy for aspergilloma complicating right pulmonary artery agenesis. Four weeks after surgery, she developed bronchial fistula and relapsed after a month. Two surgical interventions were necessary to resolve the bronchial fistula. The only solution to stop the recurrent complications was to use a greater omentum flap to cover the bronchial fistula. This surgical technique has proved effective for the first time with no complications after 5 months.   Conclusions:  Omentoplasty allows improvement of treatment results, decrease of the complication frequency due to the anatomical, functional and vascular particularities of greater omentum.
The Dynamics of Glomerular Filtration after Caesarean Section
Authors: RICHARD A. LAFAYETTE, TAHIRA MALIK, MAURICE DRUZIN, GERALDINE DERBY, BRYAN D. MYERS
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The objective of this study was to determine whether the glomerular hyperfiltration of pregnancy is maintained even after Caesarean section and, if so, to define the responsible hemodynamics. The dynamics of glomerular filtration were evaluated in 12 healthy women who had just completed an uncomplicated pregnancy and were delivered by Caesarean section. Age-matched but non-gravid female volunteers ( n = 22) served as control subjects. GFR in postpartum women was elevated above control values by 41%; 149 ± 10 versus 106 ± 3 ml/min per 1.73 m 2 , respectively ( P &lt; 0.001). In contrast, corresponding renal plasma flow was the same in the two groups, such that the postpartum filtration fraction was significantly elevated by 20%. Computation of glomerular intracapillary oncotic pressure (π GC ) from knowledge of plasma oncotic pressure and the filtration fraction revealed this quantity to be significantly reduced in postpartum women, 20.6 ± 1.7 versus 26.1 ± 2.0 mmHg in control subjects ( P &lt; 0.001). A theoretical analysis of glomerular ultrafiltration suggests that depression of π GC , the force opposing the formation of filtrate, is predominantly or uniquely responsible for the observed postpartum hyperfiltration.
Epidemiology and management of Pierre Robin sequence in East Scotland: 10-year retrospective review
Authors: Marie Wright, Felicity Mehendale, Don Urquhart
Journal: European Respiratory Journal (2014)

Pierre Robin Sequence (PRS) is a congenital disorder characterised by micrognathia, glossoptosis and cleft palate. Sequelae include upper airway obstruction (UAO) and feeding difficulties. Epidemiological data are sparse, but available evidence suggests incidence is 1:8500-1:14000 live births. No consensus exists regarding optimal management. We describe its incidence and management in East Scotland over a 10-year period.  We reviewed data from a cohort of PRS cases (2004-2013) identified by searching a regional cleft patient database and national clinical coding data. A denominator was obtained from annually published national birth statistics.  105 PRS cases were identified, giving an incidence of 1:2670 live births over a 9-year period (2013 denominator awaited). Incidence varied from 1:1260-1:4390 live births within the region, with a trend of increasing incidence with decreasing latitude. We found no incidence trends over time (median 9 cases/year, range 4-19). PRS was an isolated finding in 75%. Most prevalent syndromes were Stickler (n=7) and Treacher Collins (n=3).  Signs of UAO were present in 93%, of whom 84% were managed conservatively or with a nasopharyngeal airway (46%, median duration 4.5 months). 7% required tongue-lip adhesion or tracheostomy. 64% required nasogastric feeding (mean 13 weeks) and 8% a surgical feeding tube.  We report an incidence of PRS 3-5 times higher than previously described, validated by the presence of UAO in 93% cases. UAO can be managed non-surgically in most cases, and NPA use appeared effective within our cohort.  Funding has been granted for a national surveillance study to investigate incidence, aetiology and management across a wider population.