tbuckley/cabot-search huggingface dataset:
Traditional Chinese Medicine and the House of Lords
Authors: X P Zhai
Journal: Journal of the Royal Society of Medicine (2001)

Professor Ernst categorizes the House of Lords Science and Technology Select Committee report on complementary and alternative medicine as ‘something for everyone’ (February 2001 JRSM, pp. 55-56); but the report perpetrates a contradictory and ill-informed assessment of traditional Chinese medicine (TCM). The Committee's assessment is contradictory because, while the report affirms that there is scientific evidence for acupuncture and herbal medicine, it claims there is none for TCM. Acupuncture and herbal medicine form the basis of TCM, so how can this be?

The Select Committee did not seek evidence from a professionally qualified practitioner of TCM; indeed, in some instances it chose to listen to less than reliable witnesses and as a result received misleading and inaccurate information. There is a vast amount of pharmacological and clinical research into the therapeutic properties of Chinese herbs. They contain many of the active compounds found in Western pharmacopoeias.

The first controlled clinical trial of traditional Chinese medical plants in widespread non-exudative atopic eczema took place back in 1989. It was conducted in the UK and demonstrated a credible scientific base for the clinical efficacy of TCM1,2. The evidence from this clinical trial not only proved the effectiveness of treatment, but also indicated that Chinese herbs have platelet antiaggregatory, analgesic and antipyretic properties3. Chinese herbs are also associated with immunological changes4. Furthermore, a vast number of scientific articles support TCM with evidence of efficacy based on the results of well designed trials in the USA. Many of these have been set up or endorsed by the World Health Organization.

The effectiveness of TCM in treating infertility is also creating much interest in the UK, from both patients and fertility specialists. A controlled clinical study is urgently required. Without it, bodies like the Select Committee will continue to deem TCM unscientific and therefore unprofessional. But if they believe that science is about experience and discovery, research and confirmation then it follows that every discipline should be treated fairly.

Of course, safety is of prime importance in any clinical practice. It is therefore particularly distressing to know that people without a high standard of training are being allowed to practise complementary and alternative medicine (CAM) legally. If the Lords' report really is intended to protect the health of the public, it is indeed essential that CAM becomes well regulated, with good educational standards and training. As part of the process, the committee should revise its classification of both Chinese herbal medicine and TCM without delay.
Maxillo-mandibular surgery for obstructive sleep apnoea
Authors: C Guilleminault, M A Quera-Salva, N B Powell, R W Riley
Journal: European Respiratory Journal (1989)

Many therapeutic approaches, including mandibular surgery, have been proposed for the treatment of obstructive sleep apnoea syndrome. In the largest study of its type yet reported, 54 patients (population A) underwent mandibular surgery: 36 had palato-pharyngoplasty and inferior sagittal osteotomy of the mandible with hyoid myotomy and resuspension, and 18 (population B) had maxillo-mandibular hyoid advancement, a procedure consisting of palato-pharyngoplasty, inferior sagittal osteotomy of the mandible with hyoid myotomy and, several months later, a maxillo-mandibular osteotomy. Criteria for procedure selection and for evaluation of results were pre-set, and clinical and polygraphic follow-up occurred 6-8 months after final surgery. In population A, 32 of the 36 patients had improved; but only 20 were evaluated as "satisfactory". In contrast, all of the population B patients were judged satisfactory. Four of the population B patients received nasal continuous positive airway pressure (CPAP) before any surgery, and both approaches gave similar good polygraphic results. The degree of skeletal cranio-facial deficiencies, particularly retrognathia, is crucial for procedure selection. We describe potential procedural risks and problems.
Indium-III octreotide scintigraphy of Merkel cell carcinomas and their metastases
Authors: P. Guitera-Rovel, J. Lumbroso, M.S. Gautier-Gougis, A. Spatz, S. Mercier, A. Margulis, G. Mamelle, F. Kolb, E. Lartigau, M.F. Avril
Journal: Annals of Oncology (2001)
A TDO2-AhR Signaling Axis Facilitates Anoikis Resistance and Metastasis in Triple-Negative Breast Cancer
Authors: Nicholas C. D'Amato, Thomas J. Rogers, Michael A. Gordon, Lisa I. Greene, Dawn R. Cochrane, Nicole S. Spoelstra, Travis G. Nemkov, Angelo D'Alessandro, Kirk C. Hansen, Jennifer K. Richer
Journal: Cancer Research (2015)

The ability of a cancer cell to develop resistance to anoikis, a programmed cell death process triggered by substratum detachment, is a critical step in the metastatic cascade. Triple-negative breast cancers (TNBC) exhibit higher rates of metastasis after diagnosis, relative to estrogen-positive breast cancers, but while TNBC cells are relatively more resistant to anoikis, the mechanisms involved are unclear. Through gene expression and metabolomic profiling of TNBC cells in forced suspension culture, we identified a molecular pathway critical for anchorage-independent cell survival. TNBC cells in suspension upregulated multiple genes in the kynurenine pathway of tryptophan catabolism, including the enzyme tryptophan 2,3-dioxygenase (TDO2), in an NF-κB-dependent manner. Kynurenine production mediated by TDO2 in TNBC cells was sufficient to activate aryl hydrocarbon receptor (AhR), an endogenous kynurenine receptor. Notably, pharmacologic inhibition or genetic attenuation of TDO2 or AhR increased cellular sensitivity to anoikis, and also reduced proliferation, migration, and invasion of TNBC cells. In vivo, TDO2 inhibitor-treated TNBC cells inhibited colonization of the lung, suggesting that TDO2 enhanced metastatic capacity. In clinical specimens of TNBC, elevated expression of TDO2 was associated with increased disease grade, estrogen receptor-negative status, and shorter overall survival. Our results define an NF-κB-regulated signaling axis that promotes anoikis resistance, suggest functional connections with inflammatory modulation by the kynurenine pathway, and highlight TDO2 as an attractive target for treatment of this aggressive breast cancer subtype.
Costs of Treating and Preventing Nausea and Vomiting in Patients Receiving Chemotherapy
Authors: David J. Stewart, Simone Dahrouge, Doug Coyle, William K. Evans
Journal: Journal of Clinical Oncology (1999)

To evaluate the effect of ondansetron availability on the costs of managing nausea and vomiting.We retrospectively assessed antiemetic costs (drug costs, nursing time, pharmacy time, physician's time, supplies, and facility "hotel" costs, in 1991 Canadian dollars) for all patients who received moderately or highly emetogenic chemotherapy from 6 months before to 6 months after ondansetron became commercially available in September 1991. We compared the costs for treating patients who received ondansetron versus those who received other antiemetic regimens, the costs for treating patients in the 6 months before versus the 6 months after ondansetron commercial availability, and the costs for treating patients in the first 4 months versus the last 4 months of the study period.We found no cost differences for patients treated with ondansetron versus other antiemetic regimens. However, there was a significant reduction in emesis management costs for patients treated after versus before the availability of ondansetron: for patients treated in the last third versus first third of the study period, there was a decrease in cost per patient per month of treatment of $374 (95% confidence interval, $243 to $505). These savings were achieved through a reduction in hospital bed days and other costs associated with the prevention and more effective management of nausea and vomiting. At the same time, the number of patients who received emetogenic chemotherapy and their average age increased, presumably because of the better control of gastrointestinal toxicity.Ondansetron availability has been associated with changes in the clinical management of cancer patients receiving chemotherapy and with overall cost savings compared with previously available antiemetic therapy.
Importance of nutrition status in lung function of infants born preterm with or without bronchopulmonary dysplasia
Authors: Manuel Sánchez-Solís, Luis García-Marcos, Virginia Pérez Fernández
Journal: European Respiratory Journal (2012)

Aims: To know if nutrition status (as measured by BMI) is associated to lung function of infants born preterm (PT) with or without bronchopulmonary dysplasia (BPD)

Methods: By means of the raised volume rapid thoracoabdominal compression (RVRTC) technique, FVC, FEV0.5, FEF50, FEF75, and FEF25-75 were measured in 61 PT without BPD (65.6% male; corrected age 7.2±0.7 mo.) and in 55 PT with BPD (59.8% male; corrected age 7.75±0.9 mo.). A multiple regression analysis -stratified for BPD- was performed for BMI z-score (as calculated according to WHO values) and each lung function parameter (dependent variable), controlling for gender, gestational age, current corrected age, height, birth weight, smoking exposure in pregnancy.

Results: The coefficients of the regression analyses and their significance are shown in table.

View this table:



Conclusions: Lung function of infants 7-8 months of age, born PT without BPD, increases with BMI. This does not seem to be the case in infants of similar age born PT but with BPD.
Mitochondrial DNA Copy Number in Peripheral Blood Cells and Risk of Developing Breast Cancer
Authors: Alina Lemnrau, Mark N. Brook, Olivia Fletcher, Penny Coulson, Katarzyna Tomczyk, Michael Jones, Alan Ashworth, Anthony Swerdlow, Nick Orr, Montserrat Garcia-Closas
Journal: Cancer Research (2015)

Abstract Increased mitochondrial DNA (mtDNA) copy number in peripheral blood cells (PBC) has been associated with the risk of developing several tumor types. Here we evaluate sources of variation of this biomarker and its association with breast cancer risk in a prospective cohort study. mtDNA copy number was measured using quantitative real-time PCR on PBC DNA samples from participants in the UK-based Breakthrough Generations Study. Temporal and assay variation was evaluated in a serial study of 91 women, with two blood samples collected approximately 6-years apart. Then, associations with breast cancer risk factors and risk were evaluated in 1,108 cases and 1,099 controls using a nested case–control design. In the serial study, mtDNA copy number showed low assay variation but large temporal variation [assay intraclass correlation coefficient (ICC), 79.3%–87.9%; temporal ICC, 38.3%). Higher mtDNA copy number was significantly associated with younger age at blood collection, being premenopausal, having an older age at menopause, and never taking HRT, both in cases and controls. Based on measurements in a single blood sample taken on average 6 years before diagnosis, higher mtDNA copy number was associated with increased breast cancer risk [OR (95% CI) for highest versus lowest quartile, 1.37 (1.02–1.83); P trend = 0.007]. In conclusion, mtDNA copy number is associated with breast cancer risk and represents a promising biomarker for risk assessment. The relatively large temporal variation should be taken into account in future analyses. Cancer Res; 75(14); 2844–50. ©2015 AACR.
Invasive infections caused by Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae among children in St Petersburg, Russia
Authors: T. Kaijalainen, S.M. Kharit, A.S. Kvetnaya, K. Sirkiä, E. Herva, O.V. Parkov, H. Nohynek
Journal: Clinical Microbiology and Infection (2008)
Nucleotide sequence, function, activation, and evolution of the cryptic asc operon of Escherichia coli K12.
Authors: B G Hall, L Xu
Journal: Molecular Biology and Evolution (1992)

The cryptic asc (previous called "SAC") operon of Escherichia coli K12 has been completely sequenced. It encodes a repressor (ascG); a PTS enzyme IIasc for the transport of arbutin, salicin, and cellobiose (ascF); and a phospho-beta-glucosidase that hydrolyzes the sugars which are phosphorylated during transport (ascB). ascG and ascFB are transcribed from divergent promoters. The cryptic operon is activated by the insertion of IS186 into the ascG (repressor) gene. The ascFB genes are paralogous to the cryptic bglFB genes, and ascG is paralogous to galR. The duplications that gave rise to these paralogous genes are estimated to have occurred approximately 320 Mya, a time that predates the divergence of E. coli and Salmonella typhimurium.
Clinical profile and early follow-up of patients receiving pirfenidone in the PIONEER observational study
Authors: Raja Dhar, K.S. Satish, Sujeet Rajan, R. Vijai Kumar, Zarir Udwadia, Harjit Dumra, Murali Mohan, Rahul Namjoshi, Namita Ghag, Jaideep Gogtay
Journal: European Respiratory Journal (2014)

BACKGROUND:  PIONEER is an observational, PractIce based, Open label, Non-comparative, multicEnter study to Evaluate the efficacy, toleRability and safety of pirfenidone in idiopathic pulmonary fibrosis (IPF) patients from India.   OBJECTIVES:  To understand the clinical profile of patients prescribed pirfenidone therapy.   METHODS:  In this interim analysis, clinical profile of 90 patients on pirfenidone treatment is reported.   RESULTS:  Mean age was 60.95±11.13 years (46 males). Mean dose and duration of treatment on pirfenidone was 1031.06±360.2 mg and 29.26±20.00 weeks. Clinical features at baseline were dry cough 70 (77.78%), dyspnea on exertion 65 (72.22%), desaturation on exercise 26 (28.89%), clubbing 12 (13.33%), crackles 13 (14.44%) and crepitations/rales in 39 (43.33%) patients. High resolution computed tomography (HRCT) data was available in 88 patients, 62(70.45%) patients showed usual interstitial pneumonia (UIP)-IPF pattern and the rest had an “off-label prescription” of pirfenidone for non UIP-IPF pattern. Mean± SD baseline values of forced vital capacity (FVC) (n=74), six minute walk test (6MWT) (n=36) and diffusion capacity DL CO  (n=36) were 1.58± 0.663 L, 365.79±130.65 meters and 48.32±26.76 %. Mean change± SD in FVC (n=13 with FVC data for 48 weeks) was 0.09±0.27 L. Most common adverse events reported (5 each) were gastrointestinal, skin-related and respiratory.   CONCLUSION:  We present the baseline data for patients on pirfenidone in the PIONEER study. In a small subgroup of patients who had FVC data at 24 and 48 weeks, pirfenidone appears to stabilize lung function. Further results from the study are awaited.
Modeling of exhaled nitric oxide in relation to smoking history - A population based study
Authors: Björn Bake, Kjell Torén, Anna-Carin Olin
Journal: European Respiratory Journal (2012)

Smokers produce less NO in central airways compared to nonsmokers whereas the effect of smoking on NO concentration in the peripheral alveolar regions remain unclear, particularly if axial diffusion of NO is considered. It is also unclear to what extent exhaled NO recover among ex-smokers.  We have measured exhaled NO (FENO) at three flow rates in a population sample of 3968 subjects and the aim of the present analysis has been to try and clarify effects of current and previous smoking on exhaled NO and its central and alveolar origin and to provide reference equations for exhaled NO for healthy smokers.  The essential findings are 1) FENO of ex-smokers and nonsmokers are indistinguishable, 2) the apparent association between FENO and time since smoking cessation in ex-smokers disappears when age is taken into account, 3) smokers have higher NO concentration in the alveolar region than nonsmokers as detected when axial diffusion is considered, 4) the higher limit normal of healthy smokers is considerably lower than the corresponding limit of normal healthy nonsmokers.
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Authors: James Varani, Edmund J. Lovett
Journal: JNCI Journal of the National Cancer Institute (1982)

Murine fibrosarcoma cells that vary in their transplantability in syngeneic mice were isolated from a heterogeneous parent tumor (induced in a female C57BL/6 inbred mouse) and maintained in culture by serial passage. Several biologic properties that discriminate between the high- and low-transplantable lines (including adhesiveness, motility, and levels of chymotrypsin-like esterase activity), as well as properties that do not separate these lines (e.g., in vitro growth rates and levels of protease and glycosidase activities), were measured at periodic intervals over 2 years. Ability to induce primary tumors and to induce metastases from these tumors were evaluated at the same intervals. The high- and low-transplantable lines were also transplanted into syngeneic mice at tumorigenic doses. Isolates from primary and metastatic tumors induced in the animals were reestablished in culture and examined for the various characteristics at passages 5, 10, 20, and 30. The properties of the cells maintained continually in culture remained stable throughout the 2-year observation period. Tumor isolates showed some evidence of modulation immediately after reestablishment in culture, but by passage 10 they appeared to be identical to the prototype parent lines. These data show that the fibrosarcoma cells do not undergo continual phenotypic “drift” as has been suggested to occur with other tumor lines maintained by serial passage in animals or in culture.
Long-term changes in the COPD assessment test (CAT) after pulmonary rehabilitation
Authors: Phillippa Marns, Karen Ingram, Ria Fowler, Claire Nolan, Amy Clark, Nicholas Hopkinson, Michael Polkey, Jane Canavan, William Man
Journal: European Respiratory Journal (2011)

Introduction: The COPD assessment test (CAT) is a recently introduced, validated, patient-completed quality of life instrument that is immediately responsive to pulmonary rehabilitation (PR) [1]. The long-term effects of PR on the CAT, and whether these changes relate to more established health status instruments, are not known. We hypothesised that long-term improvements in CAT (reduced score) following PR would correlate with improvements in the self-report Chronic Respiratory Disease Questionnaire (CRDQ-SR) total score (increased score).

Method: The CAT and CRDQ-SR were recorded in 39 COPD patients before (T1), immediately after (T2) and 6-months after (T3) an 8 week outpatient PR program. On completion of the PR course, patients were offered individualised exercise advice and goal-setting, but no formal supervised exercise training. Changes in CAT and CRDQ-SR were compared from T1 to T2 and from T1 to T3. Spearman's Rank correlation was used to assess the relationship between changes in CAT and CRDQ-SR between T1 and T3.

Results: Mean (SD) age was 72 (7) and FEV1%predicted was 47 (19)%. CAT and CRDQ-SR scores at T2 and T3 were significantly improved compared to corresponding scores at T1.

![Figure][1] 



T1-T3 changes in CAT correlated significantly with changes in CRDQ-SR: r= -0.40; p=0.01.

Conclusion: Following PR, short and long-term changes in CAT score mirror the CRDQ-SR.

References: 

*   1. Dodd, JW. Thorax 2011, accepted for publication.

 [1]: pending:yes
Hypoxia-Inducible Factor 1α in Clear Cell Renal Cell Carcinoma
Authors: Tobias Klatte, David B. Seligson, Stephen B. Riggs, John T. Leppert, Maria K. Berkman, Mark D. Kleid, Hong Yu, Fairooz F. Kabbinavar, Allan J. Pantuck, Arie S. Belldegrun
Journal: Clinical Cancer Research (2007)

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays an important role in tumoral adaptation to hypoxic conditions by serving as a transcription factor for several crucial proteins, including vascular endothelial growth factor and carbonic anhydrase IX (CAIX). Here, we evaluated the significance of HIF-1 alpha in renal cell carcinoma (RCC).Immunohistochemical analysis was done on a tissue microarray constructed from paraffin-embedded primary tumor specimens from 357 patients treated by nephrectomy for RCC. Nuclear expression was evaluated by a single pathologist who was blinded to outcome. The expression levels were associated with pathologic variables and survival.HIF-1 alpha expression was greater in RCC than in benign tissue. Clear cell RCC showed the highest expression levels. In clear cell RCC, HIF-1 alpha was significantly correlated with markers of apoptosis (p21, p53), the mammalian target of rapamycin pathway (pAkt, p27), CXCR3, and proteins of the vascular endothelial growth factor family. HIF-1 alpha was correlated with CAIX and CAXII in localized, but not in metastatic RCC. HIF-1 alpha expression predicted outcome in metastatic patients: patients with high HIF-1 alpha expression (>35%) had significantly worse survival than patients with low expression (< or =35%); median survival, 13.5 versus 24.4 months, respectively (P = 0.005). Multivariate analysis retained HIF-1 alpha and CAIX expression as the strongest independent prognostic factors for patients with metastatic clear cell RCC.HIF-1 alpha is an important independent prognostic factor for patients with metastatic clear cell RCC. Because HIF-1 alpha and CAIX are independently and differentially regulated in metastatic clear cell RCC, both tumor markers can be complementary in predicting prognosis.
Is there ever a truth in evidence based medicine?
Authors: Gavan White
Journal: British Journal of Sports Medicine (2015)

Sports Doctors Australia have compiled this issue to highlight the fact that several important aspects of clinical practice in sports and exercise medicine remain unresolved and confused. Changes in ‘evidence’ can occur abruptly so that clinical practise becomes confused and confusing. Not only do clinicians feel confused about change, but imagine the plight of the patients, who get different advice from different people. There is significant concern that this will show exercise and sports medicine to have less credibility than other areas of medicine.

Dr Lorenzo Masci ( see page 1030 ) comments on the state of play with tendinopathy research and clinical application. It is thought provoking and a great example of the evolution of research and practice in tendinopathy diagnosis and management. Mr Jorgen Jevne ( see page 1031 ) presents a similarly passionate editorial …
Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese
Authors: Bo Wang, Haixia Zhou, Jun Xiao, Jing Yang, Chun Wan, Ting Yang, Xuemei Ou, Yulin Feng
Journal: European Respiratory Journal (2013)

Background: Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Genome-wide association studies (GWAS) and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and FAM13A polymorphisms in non-Asian populations.

Objectives: To investigate whether FAM13A polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in Han Chinese.

Methods: Seven single nucleotide polymorphisms (SNPs) in FAM13A gene were genotyped in a case-control study (680 COPD patients and 687 controls).

Results: Statistical analysis revealed that SNP rs7671167 was associated with COPD in former smokers with adjusted P -value of 0.026. Five SNPs (rs7671167, rs2869966, rs2869967, rs2045517, and rs6830970) were associated with FEV1/FVC ratio in the entire cohort and rs6830970 was associated with FEV1/FVC ratio in COPD cases ( P range 0.003-0.034). Six SNPs (rs7671167, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) showed strong linkage disequilibrium (r2 ≥ 0.9). Four major haplotypes were observed but showed no significant difference between case and control groups ( P = 0.2356, 0.1273, 0.6266 and 0.3006 respectively).

Conclusions: The current study suggests that the FAM13A locus might be a contributor to COPD susceptibility in Han Chinese.