tbuckley/cabot-search huggingface dataset:
Metabolism and aerobic capacity of skeletal muscle in chronic respiratory failure related to chronic obstructive pulmonary disease
Authors: B Wuyam, JF Payen, P Levy, H Bensaidane, H Reutenauer, JF Le Bas, AL Benabid
Journal: European Respiratory Journal (1992)

The calf muscle energy metabolism of 8 stable chronic obstructive pulmonary disease (COPD) patients with chronic respiratory failure (arterial oxygen tension (Pao2) 7.7 +/- 0.4 kPa or 58 +/- 3 mmHg) was studied, using 31-phosphorus magnetic resonance spectroscopy (31P MRS). MRS spectra were acquired at rest and during the course of 360 pedal movements at 20, 35 and 50% of the maximal voluntary contraction (MVC) and during recovery. Eight healthy age-matched subjects served as the control group. No significant differences between groups were observed in resting muscle, as regards intracellular pH, Pi/PCr ratio (Pi: inorganic phosphate; PCr: phosphocreatine) and the relative ATP expressed as the ratio beta ATP/PCr + Pi + PME (PME: phosphomonoester). Although effective power outputs were similar for both groups at each work level, COPD patients exhibited a higher Pi/PCr ratio than health controls (3.34 +/- 0.89 vs 0.49 +/- 0.05 at 50% MVC; p less than 0.01) and a lower pHi (6.65 +/- 0.11 vs 7.06 +/- 0.02 at 50% MVC; p less than 0.01). PCr resynthesis during recovery was slower in patients than in control subjects (t1/2 PCr 1.27 +/- 0.26 min vs 0.47 +/- 0.05 min; p less than 0.05). These results suggest impairment of aerobic capacity in a non-ventilatory working muscle, which may be due to hypoxaemia in patients with chronic respiratory failure.
Intestinal failure. Diagnosis, management and transplantation
Authors: Alastair Forbes
Journal: Gut (2008)

Edited by Langnas A, Goulet O, Quigley EMM, Tappenden KA. . Blackwell Publishing Massachusetts & Oxford, 2008, pp 390, £75.00 (Hard). ISBN 9781 4051 46371

In his complimentary foreword the intestinal failure guru Professor Stanley Dudrick describes this book as unique. While I agree with many of his positive comments, I must take him to task on this. Naturally all medical texts have a quality of uniqueness, but I think the general reader will assume uniqueness to mean that it is the only book in the field, or at least the only one of its type. This is not true given the existence of a book with the same title edited by Dr Jeremy Nightingale. This was published in California and in the UK so we cannot excuse Professor Dudrick on geographical grounds!

The two books cover similar ground, have a similar number of authors, are drawn from a similarly wide range of disciplines and are of very similar size. Admittedly one leans towards …
Imipramine in the treatment of agoraphobia: dose-response relationships
Authors: M Mavissakalian, J Perel
Journal: American Journal of Psychiatry (1985)

The authors examined dose-response relationships in 62 agoraphobic patients receiving either imipramine or placebo under double-blind conditions in conjunction with behavioral interventions. At the end of 12 weeks, patients treated with imipramine had improved significantly more than placebo patients. Results revealed that the beneficial therapeutic effect of imipramine was dose dependent and suggested that optimal response in agoraphobia may require doses of 150 mg/day or more. The results also indicated that side effects can significantly interfere with the buildup of optimal dose in agoraphobic patients treated with imipramine. The authors briefly discuss the implications of these findings for clinical practice and future research.
Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis
Authors: Taylor A. Doherty, Rachel Baum, Robert O. Newbury, Tom Yang, Ranjan Dohil, Melissa Aquino, Ashmi Doshi, Hannah H. Walford, Richard C. Kurten, David H. Broide, Seema Aceves
Journal: Journal of Allergy and Clinical Immunology (2015)
Rauscher Viral Leukemogenesis in BALB/c Mice Treated With Rabbit Antimouse Thymocyte Serum&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Benjamin V. Siegel, Jane I. Morton
Journal: JNCI Journal of the National Cancer Institute (1970)

A regimen of multiple injections of a highly immunodepressive antithymocyte serum (ATS) was effective in delaying splenomegaly in Rauscher virus-infected BALB/c mice. Whereas extensive antiserum treatment proved toxic to virus-inoculated animals, a program of 6 injections, 3 administered prior and 3 subsequent to viral inoculation, delayed the onset of deaths of infected animals by about 1–2 weeks and gave significantly increased survivals. A single injection of 0.5 ml ATS given 2 days before Rauscher virus infection had no significant effect on the leukemic process. These observations suggest that the influence of antithymocyte serum on Rauscher leukemogenesis may be a consequence of changes in numbers and properties of viral target cells.
Association of lung function and body composition in patients with metabolic syndrome
Authors: Cemile Bozdemir Ozel, Hulya Arikan, Raziye Nesrin Demirtas, Ozgen Celer, Aysen Akalin, Fusun Alatas, Melda Saglam, Naciye Vardar-Yagli, Ebru Calik-Kutukcu
Journal: European Respiratory Journal (2014)

Introduction: Metabolic syndrome (MS) has become more common relating to changes of body composition (BC) in sedantary lifestyle.

Aim: The purpose of the study was to evaluate whether BC is associated with lung function (LF) in MS.

Methods: The BC including body mass index (BMI), fat free mass (FFM), body fat (BF) and body fat percentage (BF%) was evaluated with bioelectrical impedance analysis. MIP, MEP and LF were assessed with spirometry and body plethysmography. The participants completed the International Physical Activity Questionnaire and performed a 6-minute walk test (6MWT).

Results: Of the 29 subjects (mean age: 44.03±9.7 years) in this study, 11 (37.9%) were inactive and 18 (62.1%) were minimal active. The BMI was correlated with IC (p=0.005), and negatively with FVC (p=0.031), FEV1 (p=0.025), 6MWT (p=0.017). There were positive associations of FFM with %MIP (p=0.040), MEP (p=0.033), VC (p=0.000), FVC (p=0.000), FEV1 (p=0.000), MEF75 (p=0.000), MEF50 (p=0.000) and 6MWT (p=0.003). The BF was adversely related to TLC (p=0.007), FVC (p=0.029), FEV1 (p=0.022) and 6MWT (p=0.028). The %BF was also negatively correlated to MIP (p=0.001), MEP (p=0.041), TLC (p=0.000), VC (p=0.000), IC (p=0.011), FVC (p=0.000), FEV1 (p=0.000), MEF75 (p=0.001), MEF50 (p=0.004), MEF25-75 (p=0.023) and 6MWT (p=0.000).

Conclusions: We found significant negative relationships between the different parameters of lung function with body composition, physical activity level and functional capacity in subjects with metabolic syndrome. The negative effects ofsedentary lifestyle on body composition can be reduced increasing physical activity. Therefore, lung function and functional capacity can be improved.
Bone mass after treatment for acute lymphoblastic leukemia in childhood.
Authors: K Nysom, K Holm, K F Michaelsen, H Hertz, J Müller, C Mølgaard
Journal: Journal of Clinical Oncology (1998)

PURPOSE To study bone mass after childhood acute lymphoblastic leukemia (ALL) and determine if reduced bone mass is related to previous therapy or endocrine status at follow-up. PATIENTS AND METHODS We studied 95 survivors of childhood ALL who were in first remission a median of 11 years (range, 3 to 23 years) after diagnosis and who had never been irradiated outside a cranial field. The bone mass was measured by dual-energy x-ray absorptiometry. The results were compared with data on 396 local controls. RESULTS Adjusted for sex and age, the mean whole-body bone mineral content (BMC) and bone mineral areal density (BMDA) were both significantly reduced (0.4 SDs less than the predicted mean value). This was mainly caused by reduced bone mass in the 33 participants who were aged 19 years or older at follow-up. In these young adults, the mean height for age, bone area for height, and BMC for bone area were all significantly reduced. This indicated that the reduced whole-body bone mass was caused by both reduced bone size and reduced size-adjusted bone mass. Reduced bone size was related to previous cranial irradiation. Reduced size-adjusted bone mass was not significantly related to age at diagnosis or at follow-up, length of follow-up, cranial irradiation, cumulative dose of methotrexate or corticosteroids, or endocrine status at follow-up. CONCLUSION The whole-body bone mass was reduced 11 years after diagnosis of childhood ALL. If these abnormalities remain, survivors of childhood ALL will have an increased risk for osteoporotic fractures later in life.
Severity of airways obstruction and severity of COPD, which one?
Authors: Sonia Coton, Louisa Gnatiuc, Peter Burney
Journal: European Respiratory Journal (2013)

Background 

Current guidelines define COPD in terms of obstruction (FEV1/FVC) but most scores define severity using the FEV1 which is associated with both obstruction and restriction. We have used the BOLD data to construct a severity score based on FEV1/FVC and compared this to the equivalent score using FEV1 and tested their relative ability to predict symptoms and quality of life.

Methods 

Subjects with post-BD FEV1/FVC<0.70 were classified as moderate, severe and very severe COPD using the GOLD cut-offs of post-BD FEV1 % predicted <80, <50 and <30 respectively and using the BOLD alternative cut-offs of post-BD FEV1/FVC % predicted <86, <69 and <46 respectively.

Agreement of the two classifications was assessed using a Kappa statistic. We estimated sensitivity and specificity of the GOLD criteria as a test for identifying severity of obstruction and we assessed how the two classifications correlate with reported dyspnoea, quality of life and exacerbations in subjects with obstruction.

Results 

The quadratic weighted Kappa displayed moderate agreement between the two classifications (kappa=0.6). The two classifications identify different individuals as moderate, severe and very severe as obstruction becomes more severe: sensitivity=0.7, specificity=0.9 for moderate; sensitivity= 0.6, specificity=0.9 for severe; sensitivity= 0.5, specificity=0.9 for very severe.

The two classifications had the same ability to predict dyspnoea, MMRC score, QoL and increased frequency of exacerbations among those with obstruction.

Conclusion 

Among those with airway obstruction low FEV1 and low FEV1/FVC identify different groups. Both scores predict similar levels of dyspnoea, QoL and exacerbations.
High prevalence of multidrug-resistant Pneumococcal molecular epidemiology network clones among Streptococcus pneumoniae isolates from adult patients with community-acquired pneumonia in Japan
Authors: S. Imai, Y. Ito, T. Ishida, T. Hirai, I. Ito, K. Maekawa, S. Takakura, Y. Iinuma, S. Ichiyama, M. Mishima
Journal: Clinical Microbiology and Infection (2009)
Textiloma mimicking recurrent glioblastoma: A case report.
Authors: Pedro Garciarena, Mark Daniel Anderson, Jackson Hamilton, Dawid Schellingerhout, Gregory N Fuller, Raymond Sawaya, Mark R. Gilbert
Journal: Journal of Clinical Oncology (2013)

e13044 Background: Although uncommon, materials used for dissection or to achieve hemostasis during neurosurgical procedures can cause an inflammatory reaction called textiloma that can mimic recurrent tumor. We report a case where advanced magnetic resonance (MR) imaging suggested tumor, further mimicking previous reports of clinical and conventional MR patterns of tumor progression. Methods: A 61 year-old woman underwent an initial resection of a temporal lobe glioblastoma, followed by conventional chemoradiation, although maintenance temozolomide was stopped secondary to myelotoxicity. A nodular enhancing mass near to the surgical cavity was noted 10 months after diagnosis, leading to further evaluation with advanced MR imaging. Results: Brain MRI with advanced imaging studies including MR Spectroscopy (MRS), and perfusion imaging by dynamic contract-enhanced (DCE), and dynamic contrast susceptibility (DSC) were performed. There was progressive enlargement of an enhancing nodule in the wall of the resection cavity. MRS demonstrated an elevated choline-to-creatine ratio (approximately 2:1), while the DSC imaging demonstrated a mild amount of leak with a corrected cerebral blood volume value of about 1.93, and negative enhancement integral value 1.67. DCE demonstrated mild vascularity and mild-to-moderate leak, with an elevated peak enhancement integral value of ~22%. These imaging findings suggested recurrent GBM rather than post-treatment change. The mass was resected. Pathologic review showed both textiloma and radiation necrosis. Recurrent glioblastoma was not identified. Conclusions: Although very unusual, textiloma should be considered in the differential diagnosis of any growing mass lesion close to a surgical bed. Reparative granulomata show many of the hallmarks of cancer, including neovascularization, rapid growth and high lipid turnover, making it difficult to distinguish such lesions from true neoplasm, even with advanced imaging, without resorting to histology. Advanced imaging performs best in distinguishing conventional post-treatment change from tumor recurrence. This case highlights the major influence of surgical technique on postoperative imaging appearance.
Population pharmacokinetics (PK) of riociguat in patients (pts) with renal and hepatic impairment
Authors: Soundos Saleh, Corina Becker, Reiner Frey, Wolfgang Mueck
Journal: European Respiratory Journal (2014)

Background:  Riociguat, an oral soluble guanylate cyclase stimulator, is approved for the treatment of pulmonary arterial hypertension and persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) after surgical treatment or inoperable CTEPH.   Aims:  To characterize the population PK (PopPK) of riociguat in pts with renal and hepatic impairment.   Methods:  Plasma and urine samples were collected from pts in four Phase I studies; two renal impairment (n=64) and two hepatic impairment (n=64) studies, including smokers (n=56) and non-smokers (n=72). A single oral dose of riociguat 1.0 or 0.5 mg was administered. Nonlinear mixed-effects modeling was used to develop a PopPK model for riociguat and its metabolite M1. A combined, two-compartment model for riociguat and M1 was developed. Riociguat and M1 clearance (CL) was split into a renal part (filtration and excretion) and a non-renal part; the non-renal part for riociguat was split into its metabolism to M1 and a remaining non-renal part.   Results:  The PK of riociguat was described well by a two-compartment model. Total riociguat CL (1.912 L/h) was dominated by its metabolism to M1 (1.2 L/h). Renal CL (0.242 L/h) was mainly determined by filtration (0.174 L/h). Renal impairment reduced riociguat and M1 renal CL. Smoking increased riociguat metabolism to M1 by 3.5-fold. No effect of hepatic function biomarkers and Child–Pugh classification was found on riociguat or M1 CL.   Conclusions:  Riociguat and M1 renal CL was reduced by renal impairment. Similar values for the non-renal (non-metabolism) CL of riociguat were estimated in all groups; non-renal CL was increased in smokers.
The role of regional distribution (RD) of body fat mass (BFM) in fat-bone interactions in men with chronic obstructive pulmonary disease (COPD)
Authors: Sviatlana Lemiasheuskaya, Alexander Makarevich, Alla Shepelkevich, Natalia Vasileva
Journal: European Respiratory Journal (2012)

The aim: Evaluation of the relationships between RD of BFM and TNF-α, some hormones and markers of bone metabolism.

Methods: We used DEXA to analyze RD of BFM. We determined: serum leptin (L), testosterone free (TF), TNF-α, parathyroid hormone (PTH), beta-crosslaps (beta-CTX) and osteocalcin. We examined 83 COPD pts (40-70 yrs old) and control group – 15 healthy comparable men. The COPD pts were subdivided into 3 groups (GOLD).

Results: Fat mass (FM) in Android region (A) positively correlated with TNF-α (r=0.33, p=0.02) in all pts group. Trunk and Arms FM were positively related to L (r=0.36 and r=0.35; respectively) in all pts group. L level exerted negative influence on bone mineral density (BMD) in lumbar spine (r=-0.43, p=0.001), but not at femoral necks in total group. We found the positive correlations between beta-CTX and total FM (r=0.33) and FM in A (r=0.32) in all pts group. The total, arms, legs and trunk FM, FM in Android and Gynoid (G) regions were increased in pts with a lower level of TF (p<0.05). Loss of BMD positively correlated (p<0.05) to loss of BMI, A/G ratio, FM in all body regions, PTH, calcium ionized and was inversely related with L level in all pts group. Although these pts had decrease of BMD, BMI was increased (29.4 in pts with osteopenia and 24.7 kg/m2 – with osteoporosis). Lowering of BMD might result from other factors, such as TNF-α and some hormones which are produced by the adipose tissue.

Conclusion: The study of RD of adipose tissue in the patient's body is more informative than BMI for assessing the likelihood of developing osteoporosis in men with COPD.
Chemokine profiles of A549 human alveolar epithelial cells that underwent epithelial-mesenchymal transition by TGF-b and/or TNF-a
Authors: Masafumi Horie, Yasuhiro Yamauchi, Akira Saito, Taisuke Jo, Yu Mikami, Hajime Takizawa, Takahide Nagase, Tadashi Kohyama
Journal: European Respiratory Journal (2012)

Rationale: Epithelial-mesenchymal transition (EMT) is supposed to be implicated in the pathogenesis of lung fibrosis through enhanced TGF-b1 signaling. TNF-a has also been implicated in tissue fibrosis. Recently, TGF-b induced EMT is augmented by TNF-a, suggesting that enhanced EMT by TNF-a may be important in the pathological processed of lung diseases. However, the mechanism of enhanced EMT by TNF-a has not been fully elucidated. Therefore, we evaluated the cytokine/ chemokine profiles of the cells that underwent EMT by TGF-b and/or TNF-a.  Methods: A549 cells were incubated for 48 hours with 5 ng/ml of TGF-b1, 10 ng/ml of TNF-a, or TGF-b1 and TNF-a to undergo EMT. After 48 hours incubation, growth medium was changed to serum-free medium, and the supernatants were collected at 48 hours. Cytokine/ chemokine array was performed using Ray Bio human cytokine array V. Relative values were quantified by densitometry, and normalized to that obtained in non-treated sample.  Results: TNF-a induced production of inflammatory chemokines, such as RANTES and MCP-1. TGF-b induced production of inflammatory chemokines, including GM-CSF, GRO, GRO-a, MCP-2, and MCP-3. Simultaneous stimulation with TNF-a and TGF-b induced production of GM-CSF, GRO, GRO-a, IL6, MCP-1, RANTES, and these effects were enhanced on the production of GRO, GRO-a, IL-8, and MCP-1.  Conclusion: The cells treated with TGF-b1 or TNF-a have different chemokine profile, and the effect on chemokines production was enhanced by the combination with TGF-b1 and TNF-a. This study might contribute to understanding mechanism of EMT enhanced by TNF-a and pathogenesis of lung fibrosis.
Emerging role of microRNAs to tackle drug resistance in pancreatic cancer
Authors: Albrecht Neesse, Thomas M Gress
Journal: Gut (2015)

Despite the recent emergence of novel chemotherapy regimen such as nab-paclitaxel/gemcitabine and FOLFIRINOX (folinic acid, fluorouracil, irinotecan and oxaliplatin), pancreatic ductal adenocarcinoma (PDA) is characterised by a poor response to chemotherapy and radiotherapy. Therefore, it remains a challenge for clinicians and scientists likewise to overcome resistance to treatment. PDA silently develops from preneoplastic lesions (PanINs I–III) to invasive cancer over a long period of time. A number of genetic mutations have been identified and well characterised during the evolution of PDA, such as the Kras oncogene, and tumour suppressor genes p16 , p53 and DPC4 . In addition to genetic mutations, epigenetic modifications and complex alterations within the tumour microenvironment give rise to cell autonomous and non-cell autonomous mechanisms of therapy resistance. Over the past years, it has emerged that therapeutic resistance is, at least in part, mediated by cancer stem cells (CSCs) that are perpetuated within a small fraction of cells within the tumour bulk.1 Stemness and epithelial to mesenchymal transition are closely related on a molecular level and …
Communicating About Chemotherapy-Induced Nausea and Vomiting: A Comparison of Patient and Provider Perspectives
Authors: John M. Salsman, Steven M. Grunberg, Jennifer L. Beaumont, Miriam Rogers, Diane Paul, Marla L. Clayman, David Cella
Journal: Journal of the National Comprehensive Cancer Network (2012)

Despite recent progress, chemotherapy-induced nausea and vomiting (CINV), especially delayed CINV, continues to be a problem. Delayed CINV is underestimated and perceived differently by providers and patients. Communication between providers and patients about this side effect may help improve outcomes. This study identifies patients' and providers' perceptions of management and barriers to quality CINV care. Provider and patient versions of a Nausea and Vomiting Management Barriers Questionnaire were developed to address potential barriers. Providers and patients were given opportunities to add detail in open-ended questions. Providers were recruited through the NCCN and the Oncology Nursing Society mailing lists. Patients who received at least 2 cycles of chemotherapy and experienced CINV were recruited through a consortium of advocacy groups. Both providers (n = 141) and patients (n = 299) completed the survey. Providers (41%) and patients (42%) agreed medication side effects were a concern, but more patients (63%) than providers (36%) tried to limit the number of medications taken (P < .0001). Many providers (67%) spontaneously reported barriers to managing CINV, with financial and patient-related factors among the most common. Few patients (10%) reported cost as a barrier, but 37% endorsed the desire "to be strong by not complaining." Barriers to communication and quality care of CINV differ between caregivers and patients. Addressing misconceptions and establishing mutually consistent goals will lead to more effective overall care.
Accused Alabama doctors each wrote an opioid prescription every four minutes on average
Authors: Owen Dyer
Journal: BMJ (2015)

Federal prosecutors have disclosed the indictment against two Alabama partners who wrote tens of thousands of prescriptions for opioid painkillers each year, many of which, the government alleges, went to people with no medical need for the drugs. But the prosecutors have redacted the names of the drug companies that paid the doctors for their services.

Xiulu Ruan and John Patrick Couch were charged two months ago with conspiracy to distribute controlled substances not for a legitimate medical purpose and conspiracy to commit healthcare fraud.

Their practice, which operated its own pharmacy on the premises, was in the top 10 buyers nationally for several commonly misused opioids, including oxymorphone, fentanyl, morphine, and methadone.

In 2014 Ruan wrote 34 883 prescriptions for controlled substances, which would represent more than one every four minutes if …
Gates funds surveillance site to prevent next big epidemic
Authors: A. Gulland
Journal: BMJ (2015)

The US philanthropist Bill Gates has announced a $75m (£50m; €67m) grant to fund six disease surveillance sites in poor countries, aimed at catching the next large scale epidemic early.

Gates, a big funder of global health projects through his eponymous foundation, told BBC Radio 4’s Today news program that the grant would fund laboratories in sub-Saharan Africa and Asia.

He said, “[They] will do very in-depth analysis of what’s killing children and mothers. The beauty of this endeavor is that it really …