tbuckley/cabot-search huggingface dataset:
Caring for the orphan's orphan: treatment of patients with portopulmonary hypertension
Authors: S. M. Kawut
Journal: European Respiratory Journal (2007)

Patients with portopulmonary hypertension (PPHTN) are incredibly unfortunate. By definition, these patients have portal hypertension, leading to well-known life-threatening gastrointestinal, neurological, infectious, haematological and renal complications requiring liver transplantation for cure.

If this were not enough, these patients also have pulmonary arterial hypertension (PAH). The coexistence of portal hypertension and PAH frequently makes patients with this rare (or “orphan”) condition medical “untouchables”. PPHTN patients with progressive hepatic dysfunction and other complications are often deemed to be too “high-risk” for placement of a transjugular intrahepatic portosystemic shunt or liver transplantation, making them destined for a poor outcome. Even those who may be acceptable candidates for liver transplantation commonly face a complicated perioperative course.

The situation is not much better from the vantage of their lung disease, despite these patients having the third most common form of PAH in a recent population-based epidemiological study from France 1. While there is some evidence regarding medications which should be avoided in PPHTN 2, therapeutic approaches used to treat other forms of PAH have never been trialled in PPHTN, are potentially complicated by coexistent liver disease, and are used in PPHTN without the evidence base which now exists for other types of PAH.

Many individuals with PPHTN have a history of (or are currently) using alcohol or illicit drugs, addictions commonly linked to the aetiology of their liver disease, and some have HIV infection, all accompanied by significant social stigma. These comorbidities often further limit access to specialised centres and available treatments. The sum of these burdens and the high toll of the disease have proved significant obstacles to successful advocacy on behalf of this patient group. Who can blame industry sponsors, scientific advisory committees and regulatory boards for excluding these patients from clinical trials of new therapies for PAH?

It is against …
Intracolonic administration of zileuton, a selective 5-lipoxygenase inhibitor, accelerates healing in a rat model of chronic colitis.
Authors: X Bertran, J Mane, F Fernandez-Banares, E Castella, R Bartoli, I Ojanguren, M Esteve, M A Gassull
Journal: Gut (1996)

BACKGROUND: 5-Lipoxygenase products play a part in inflammatory response. AIMS: The effect of intracolonic administration of zileuton (a 5-lipoxygenase inhibitor) on colonic damage and eicosanoid local release was assessed in a rat model of colitis. METHODS: Ninety rats with trinitrobenzenesulphonic acid induced colitis were randomised to receive placebo, 5-aminosalicylic acid (50 mg/kg), or zileuton (50 mg/kg) intracolonically for four weeks. Local eicosanoid release was monitored by intracolonic dialysis throughout the study. The colon was removed for macroscopic and histological assessment at weeks 1, 2, and 4 after colitis induction in 10 rats of each group. RESULTS: Zileuton significantly reduced macroscopic damage score after four weeks of treatment in comparison with the other two groups (p = 0.034). In addition, zileuton administration significantly increased the intracolonic release of both thromboxane B2 at week 1 (p = 0.05) and prostaglandin E2 at weeks 2 and 4 (p &lt; 0.05). Zileuton and 5-aminosalicylic acid decreased leukotriene B4 release by 90% at day 3. CONCLUSIONS: Intracolonic zileuton, compared with 5-aminosalicylic acid and placebo, seems to improve the course of the disease in a model of chronic colitis. This effect may be related to an increased and maintained production of prostaglandin E2 together with inhibition of leukotriene B4 synthesis.
Effect of environmental tobacco smoke on cough in children with a history of tonsillectomy or adenoidectomy
Authors: Y Chen, DC Rennie, LA Lockinger, JA Dosman
Journal: European Respiratory Journal (1998)

We examined the possible impact of tonsillectomy or adenoidectomy (T/A) on the relationship between environmental tobacco smoke (ETS) exposure and respiratory outcomes. This study was conducted in Humboldt, Saskatchewan, in 1993. The target population included all residents aged 6-17 yrs. Of the 1,019 eligible subjects, 892 participated (88%). Estimates of ETS exposure were based on the reported smoking habits of the children's household members. We defined current cough as a positive response to the question: "Does this child usually have a cough?". Information also included morning cough, night cough and a history of T/A. For children with no history of T/A, the prevalence of current cough was 8.9%, 12.2% and 14.5% for those living in families with 0, 1, and 2+ smokers respectively. The corresponding prevalence was 7.0%, 30.2% and 36.8% for children with history of T/A. Similar effects of ETS exposure were observed on morning cough and night cough. The results did not change significantly when we used various ETS measures and controlled for confounding factors. Compared to children living in nonsmoking families and without history of T/A, the adjusted odds ratio for children with a history of T/A was 7.19 (p&lt;0.001) if they were living in families smoking &gt;20 cigarettes x day(-1) at home. The corresponding odds ratio was only 1.64 (p=0.11) for children without a history of T/A. We concluded that children living in smoking family were more likely to cough than those living in nonsmoking families and tonsillectomy or adenoidectomy increased the apparent influence of environmental tobacco exposure on cough.
Loperamide has antisecretory activity in the human jejunum in vivo.
Authors: S Hughes, N B Higgs, L A Turnberg
Journal: Gut (1984)

We investigated the possibility that loperamide might influence absorption and secretion in the human jejunum in vivo. Using a triple lumen tube perfusion technique in healthy normal volunteers we showed that loperamide did not affect net absorption of water or electrolytes under basal condition. When secretion was induced by prostaglandin E2, however, loperamide significantly reduced that secretion and in three out of six subjects secretion was abolished. Loperamide was effective when it was given either before or after secretion had been initiated. The results lend support to the suggestion that the antidiarrhoeal activities of loperamide may include an antisecretory effect.
Cetuximab Plus Irinotecan in Heavily Pretreated Metastatic Colorectal Cancer Progressing on Irinotecan: MABEL Study
Authors: Hansjochen Wilke, Robert Glynne-Jones, Josef Thaler, Antoine Adenis, Peter Preusser, Enrique Aranda Aguilar, Matti S. Aapro, Regina Esser, Anja H. Loos, Salvatore Siena
Journal: Journal of Clinical Oncology (2008)

Purpose This large, multinational study aimed to confirm in a community practice setting the efficacy and safety of cetuximab plus irinotecan in patients with epidermal growth factor–expressing metastatic colorectal cancer (mCRC) who had recently failed an irinotecan-containing regimen. Patients and Methods The primary objective was to determine the progression-free survival (PFS) rate at 12 weeks. The initial cetuximab dose was 400 mg/m 2 and was followed weekly by 250 mg/m 2 ; irinotecan (according to prestudy regimen) was given weekly (125 mg/m 2 weekly for 4 of 6 weeks), every 2 weeks (180 mg/m 2 each), or every 3 weeks (350 mg/m 2 each). Results The intention-to-treat/safety population comprised 1,147 treated patients who received irinotecan weekly (n = 93); every 2 weeks (n = 670); every 3 weeks (n = 356); or another dose (n = 28). The PFS rate at 12 weeks was 61%, and the median survival was 9.2 months. Treatment was generally well tolerated. The most common treatment-related grades 3 to 4 adverse events were diarrhea (19%), neutropenia (10%), rash (7%), and asthenia (6%). The rate of grades 3 to 4 infusion-related reactions (IRRs; composite adverse event category) was 1% for patients who received both antihistamine and corticosteroid premedication. Conclusion Tolerability (except IRR incidence), PFS rate, and overall survival rate were in line with previous results. At 1%, the rate of IRRs in patients who received prophylactic premedication with both antihistamine and corticosteroid is lower than previously reported. MABEL clearly confirms in a community practice setting the efficacy and safety of cetuximab plus irinotecan in the treatment of mCRC.
Cultured keratinocyte allografts and wound healing in severe recessive dystrophic epidermolysis bullosa
Authors: John A. McGrath, Olivia M.V. Schofield, Akemi Ishida-Yamamoto, Anthony O’Grady, Bryan J. Mayou, Harshad Navsaria, Irene M. Leigh, Robin A.J. Eady
Journal: Journal of the American Academy of Dermatology (1993)
Comprehensive genotyping of the USA national maize inbred seed bank
Authors: Maria C Romay, Mark J Millard, Jeffrey C Glaubitz, Jason A Peiffer, Kelly L Swarts, Terry M Casstevens, Robert J Elshire, Charlotte B Acharya, Sharon E Mitchell, Sherry A Flint-Garcia, Michael D McMullen, James B Holland, Edward S Buckler, Candice A Gardner
Journal: Genome biology (2013)

Genotyping by sequencing, a new low-cost, high-throughput sequencing technology was used to genotype 2,815 maize inbred accessions, preserved mostly at the National Plant Germplasm System in the USA. The collection includes inbred lines from breeding programs all over the world.The method produced 681,257 single-nucleotide polymorphism (SNP) markers distributed across the entire genome, with the ability to detect rare alleles at high confidence levels. More than half of the SNPs in the collection are rare. Although most rare alleles have been incorporated into public temperate breeding programs, only a modest amount of the available diversity is present in the commercial germplasm. Analysis of genetic distances shows population stratification, including a small number of large clusters centered on key lines. Nevertheless, an average fixation index of 0.06 indicates moderate differentiation between the three major maize subpopulations. Linkage disequilibrium (LD) decays very rapidly, but the extent of LD is highly dependent on the particular group of germplasm and region of the genome. The utility of these data for performing genome-wide association studies was tested with two simply inherited traits and one complex trait. We identified trait associations at SNPs very close to known candidate genes for kernel color, sweet corn, and flowering time; however, results suggest that more SNPs are needed to better explore the genetic architecture of complex traits.The genotypic information described here allows this publicly available panel to be exploited by researchers facing the challenges of sustainable agriculture through better knowledge of the nature of genetic diversity.
HIV-1 Drug Resistance Emergence among Breastfeeding Infants Born to HIV-Infected Mothers during a Single-Arm Trial of Triple-Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission: A Secondary Analysis
Authors: Clement Zeh, Paul J. Weidle, Lillian Nafisa, Humphrey M. Lwamba, Jully Okonji, Emily Anyango, Philip Bondo, Rose Masaba, Mary Glenn Fowler, John N. Nkengasong, Michael C. Thigpen, Timothy Thomas
Journal: PLoS Medicine (2011)

Nevirapine and lamivudine given to mothers are transmitted to infants via breastfeeding in quantities sufficient to have biologic effects on the virus; this may lead to an increased risk of a breastfed infant's development of resistance to maternal antiretrovirals. The Kisumu Breastfeeding Study (KiBS), a single-arm open-label prevention of mother-to-child HIV transmission (PMTCT) trial, assessed the safety and efficacy of zidovudine, lamivudine, and either nevirapine or nelfinavir given to HIV-infected women from 34 wk gestation through 6 mo of breastfeeding. Here, we present findings from a KiBS trial secondary analysis that evaluated the emergence of maternal ARV-associated resistance among 32 HIV-infected breastfed infants.All infants in the cohort were tested for HIV infection using DNA PCR at multiple study visits during the 24 mo of the study, and plasma RNA viral load for all HIV-PCR-positive infants was evaluated retrospectively. Specimens from mothers and infants with viral load >1,000 copies/ml were tested for HIV drug resistance mutations. Overall, 32 infants were HIV infected by 24 mo of age, and of this group, 24 (75%) infants were HIV infected by 6 mo of age. Of the 24 infants infected by 6 mo, nine were born to mothers on a nelfinavir-based regimen, whereas the remaining 15 were born to mothers on a nevirapine-based regimen. All infants were also given single-dose nevirapine within 48 hours of birth. We detected genotypic resistance mutations in none of eight infants who were HIV-PCR positive by 2 wk of age (specimens from six infants were not amplifiable), for 30% (6/20) at 6 wk, 63% (14/22) positive at 14 wk, and 67% (16/24) at 6 mo post partum. Among the 16 infants with resistance mutations by 6 mo post partum, the common mutations were M184V and K103N, conferring resistance to lamivudine and nevirapine, respectively. Genotypic resistance was detected among 9/9 (100%) and 7/15 (47%) infected infants whose mothers were on nelfinavir and nevirapine, respectively. No mutations were detected among the eight infants infected after the breastfeeding period (age 6 mo).Emergence of HIV drug resistance mutations in HIV-infected infants occurred between 2 wk and 6 mo post partum, most likely because of exposure to maternal ARV drugs through breast milk. Our findings may impact the choice of regimen for ARV treatment of HIV-infected breastfeeding mothers and their infected infants.
TCT-581 Multislice Computed Tomography Angiography as a Non-invasive Angiographic and Functional Assessment of the 18-Months Performance of a Novel Radiolucent Bio-resorbable Coronary Scaffolding Device (ABSORB Cohort B Trial)
Authors: Koen Nieman, Yoshinobu Onuma, Robert-Jan van Geuns, Bernard De Bruyne, Leif Thuesen, Peter Smits, Jacques Koolen, Dougal McCLean, Bernard Chevalier, Ian Meredith, John Ormiston, Patrick Serruys
Journal: Journal of the American College of Cardiology (2012)
Mechano‐physical and biophysical properties of power‐driven scalers: driving the future of powered instrument design and evaluation
Authors: Simon C. Lea, A. Damien Walmsley
Journal: Periodontology 2000 (2009)

This review has highlighted the importance of standardizing future investigations to enable more meaningful interstudy comparisons to be made. This report also makes recommendations for factors that should be considered and incorporated into future investigations, both in vitro and in vivo, in order to achieve more standardization. These recommendations are listed below.
Two-Dimensional in-Vitro Studies of Femoral Arterial Walls of the Dog
Authors: FRANÇoise M. L. ATTINGER
Journal: Circulation Research (1968)

Analyses of the vascular system have characteristically been based on assumptions that the vessel wall is isotropic and that its properties and behavior can be linearized. To test the validity of these assumptions, excised arteries of dogs were submitted to stepwise strains tangentially and longitudinally during conditions of control, vasoconstriction, and inhibition of muscle metabolism. These strains were recorded simultaneously with the associated stresses, and the relations between stress and strain were studied during both dynamic-and steady-strain states. The vessels were anisotropic within most of the physiological ranges of tangential and longitudinal stress and strain. During control conditions the tangential modulus of elasticity was higher than the longitudinal; during vasoconstriction the situation was reversed for wall tensions corresponding to a blood pressure equal to or smaller than 190 mm Hg; however, above this value isotropic behavior prevailed. Vasoconstriction increased the non-linearity of the stress-strain relation, and decreased the modulus of elasticity of the arterial wall. The viscoelastic properties of the femoral artery were found to be different tangentially and longitudinally, as evidenced by a much larger amount of stress relaxation in the former direction than in the latter.
Potentiation by Nitric Oxide of Cyclosporin A and FK506-Induced Apoptosis in Renal Proximal Tubule Cells
Authors: SONSOLES HORTELANO, MANUELA CASTILLA, ANA M. TORRES, ALBERTO TEJEDOR, LISARDO BOSCA[Combining Acute Accent]
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Proximal tubular epithelial cells (PTEC) exhibit a high sensitivity to undergo apoptosis in response to proinflammatory stimuli and immunosuppressors and participate in the onset of several renal diseases. This study examined the expression of inducible nitric oxide (NO) synthase after challenge of PTEC with bacterial cell wall molecules and inflammatory cytokines and analyzed the pathways that lead to apoptosis in these cells by measuring changes in the mitochondrial transmembrane potential and caspase activation. The data show that the apoptotic effects of proinflammatory stimuli mainly were due to the expression of inducible NO synthase. Cyclosporin A and FK506 inhibited partially NO synthesis. However, both NO and immunosuppressors induced apoptosis, probably through a common mechanism that involved the irreversible opening of the mitochondrial permeability transition pore. Activation of caspases 3 and 7 was observed in cells treated with high doses of NO and with moderate concentrations of immunosuppressors. The conclusion is that the cooperation between NO and immunosuppressors that induce apoptosis in PTEC might contribute to the renal toxicity observed in the course of immunosuppressive therapy.
Unacceptable variation in abdominoperineal excision rates for rectal cancer: time to intervene?
Authors: E Morris, P Quirke, J D Thomas, L Fairley, B Cottier, D Forman
Journal: Gut (2008)

<h3>Objective:</h3> To determine the variation in the rates of use of abdominoperineal excision (APE) by cancer network, hospital trust and surgeon across England between 1998 and 2004 and determine if any variation could be explained by differences in patient characteristics such as stage of disease, age, gender or socioeconomic deprivation. <h3>Design:</h3> Retrospective study of a population-based dataset comprised of cancer registry and hospital episode statistics data. <h3>Setting:</h3> All NHS providers of rectal cancer surgery within England. <h3>Patients:</h3> 31 223 patients diagnosed with rectal cancer and receiving a major abdominal procedure within the NHS in England between 1998 and 2004. <h3>Main outcome measure:</h3> Rates and odds of use of APE were determined in relation to patient case-mix and each patient’s managing surgeon, trust and cancer network. <h3>Results:</h3> The rate of use of APE decreased from 30.5% in 1998 to 23.0% in 2004. Males, the economically deprived and those managed by surgeons operating on fewer than seven rectal cancer cases per year were all significantly more likely to receive an APE. There were also significant variations in the odds of receiving an APE over time and between individual surgeons and hospital trusts independently of patient case-mix. <h3>Conclusions:</h3> Over the study period the use of APE decreased but statistically significant variation was observed in its application independently of case mix. Reducing this variation will remove inequalities, reduce colostomy rates, and improve outcomes in rectal cancer. Rates of APE use could be a national performance measure.
A blueprint for symptom scales and responses: measurement and reporting
Authors: K W Wyrwich
Journal: Gut (2004)

Measurement of symptom status among patients with GORD has, to date, been conducted in a variety of ways. We applied a cognitive psychology framework, as well as reviewed the current psychometric literature, to develop a blueprint for the best methods of measuring and reporting symptoms of patients with gastro-oesophageal reflux disease (GORD). Our review suggests that the seven point scale with word anchors for each point is likely to afford better reliability, improved sensitivity to change in GORD symptoms, and greater ease in administration compared with visual analogue or other types of response scales.
Economic evaluation of antibiotic prophylaxis in small-cell lung cancer patients receiving chemotherapy: an EORTC double-blind placebo-controlled phase III study (08923)
Authors: V.C.G. Tjan-Heijnen, S. Caleo, P.E. Postmus, A. Ardizzoni, J.T.M. Burghouts, E. Buccholz, B. Biesma, T. Gorlia, R. Crott, G. Giaccone, C. Debruyne, C. Manegold
Journal: Annals of Oncology (2003)
The effect of pulmonary rehabilitation on health-related quality of life in asthmatic children
Authors: Katerina Neumannova, Jakub Zatloukal, Dana Dvorakova, Jana Rydlova
Journal: European Respiratory Journal (2013)

Introduction  Bronchial asthma disease (BA) can lead to decreased quality of life, which can negatively influence children’s activity of daily living and their participation in various activities and for that reason complex treatment is essential for minimizing physical, emotional and social impairments resulting from BA.  Aim  To evaluate an effect of a 4-week pulmonary rehabilitation (PR) during inpatient spa treatment on health-related quality of life (HRQL) in children with BA.  Methods  Forty seven children (aged 12.7±2.7 years) with mild intermittent BA attended the 4-week PR including education, respiratory physiotherapy and exercise training in group sessions during the inpatient spa treatment. Children underwent lung function test (LFT), 6-minute walking test (6MWT), assessment of HRQL with Paediatric asthma quality of life questionnaire (PAQLQ) at baseline and at the end of treatment.  Results  Although values of LFT were normal in BA children, HRQL was lower at baseline. After completing the 4-week PR a significant improvement was achieved in all PAQLQ domains and also in vital capacity and 6MWT [tab.1].  Conclusion  PR led to a significant improvement in physical conditioning, health and functional status of BA children. Therefore, PR is an important part of complex treatment in children with mild BA.  Supported by grant of the Palacky University: FTK_2012:023.
Reverse transcriptase-dependent and -independent phases of infection with mouse mammary tumor virus: implications for superantigen function.
Authors: W Held, G A Waanders, H Acha-Orbea, H R MacDonald
Journal: The Journal of Experimental Medicine (1994)

Mouse mammary tumor virus (MMTV) encodes a superantigen (SAg) that promotes stable infection and virus transmission. Upon subcutaneous MMTV injection, infected B cells present SAg to SAg-reactive T cells leading to a strong local immune response in the draining lymph node (LN) that peaks after 6 d. We have used the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (AZT) to dissect in more detail the mechanism of SAg-dependent enhancement of MMTV infection in this system. Our data show that no detectable B or T cell response to SAg occurs in AZT pretreated mice. However, if AZT treatment is delayed 1-2 d after MMTV injection, a normal SAg-dependent local immune response is observed on day 6. Quantitation of viral DNA in draining LN of these infected mice indicates that a 4,000-fold increase in the absolute numbers of infected cells occurs between days 2 and 6 despite the presence of AZT. Furthermore MMTV DNA was found preferentially in surface IgG+ B cells of infected mice and was not detectable in SAg-reactive T cells. Collectively our data suggest that MMTV infection occurs preferentially in B cells without SAg involvement and is completed 1-2 d after virus challenge. Subsequent amplification of MMTV infection between days 2 and 6 requires SAg expression and occurs in the absence of any further requirement for reverse transcription. We therefore conclude that clonal expansion of infected B cells via cognate interaction with SAg-reactive T cells is the predominant mechanism for increasing the level of MMTV infection. Since infected B cells display a memory (surface IgG+) phenotype, both clonal expansion and possibly longevity of the virus carrier cells may contribute to stable MMTV infection.