tbuckley/cabot-search huggingface dataset:
Comparison of the acute effects on gas exchange of nasal ventilation and doxapram in exacerbations of chronic obstructive pulmonary disease.
Authors: R. M. Angus, A. A. Ahmed, L. J. Fenwick, A. J. Peacock
Journal: Thorax (1996)

BACKGROUND: Nasal intermittent positive pressure ventilation (NIPPV) is useful in exacerbations of chronic obstructive pulmonary disease (COPD) complicated by ventilatory failure. The effects of NIPPV were compared with those of the respiratory stimulant doxapram on gas exchange in patients with COPD and acute ventilatory failure. METHODS: Patients admitted with acute exacerbations of COPD and type 2 respiratory failure (Pao2 &lt; 8 kPa and PaCO2 &gt; 6.7 kPa) who did not improve with conventional treatment were randomised to receive either NIPPV or intravenous doxapram. Blood gas tensions were monitored for four hours. RESULTS: In nine patients who received NIPPV the arterial PaO2 improved from a mean (SE) of 5.9 (0.4) kPa to a maximum of 8.1 (0.6) kPa which was maintained at four hours. Eight patients who received doxapram had a similar baseline Pao2 of 5.6 (0.4) kPa which rose to a maximum of 7.3 (0.5) kPa but this was not maintained at four hours. The improvement in Pao2 in patients on NIPPV was accompanied by a fall in Paco2 but, in contrast, in those who received doxapram there was no improvement in Paco2. CONCLUSIONS: NIPPV may be more effective than doxapram in the management of acute ventilatory failure complicating COPD.
Impairment of heart action following various methods of surgical denervation
Authors: T. J. Otto, P. C. Cheah
Journal: Thorax (1970)

Surgical cardiac denervation was carried out in 25 greyhounds and their responses to exercise, propranolol, and atropine were observed between one and three months afterwards. Our experiments confirm that a denervated heart shows delayed and diminished response to exercise and no response to atropine and propranolol. We found that no cardio-circulatory mechanism seems to be present in the cavae and that hearts can be `selectively9 denervated to produce an isolated increase in right ventricular pressure which is presumably due to severance of inhibitory fibres leading to the right ventricle, so that the augmentory fibres are unopposed.
Preventing Future Cancers by Testing Women With Ovarian Cancer for<i>BRCA</i>Mutations
Authors: Janice S. Kwon, Molly S. Daniels, Charlotte C. Sun, Karen H. Lu
Journal: Journal of Clinical Oncology (2009)

Women with ovarian cancer have a 10% probability of carrying a BRCA mutation. If a mutation is identified, unaffected family members can undergo genetic testing and cancer risk-reducing strategies. We estimated the net health benefits and cost-effectiveness of different criteria for BRCA mutation testing in women with ovarian cancer, and the downstream benefits for their first-degree relatives (FDRs).We developed a Markov Monte Carlo simulation model to compare four criteria for BRCA testing in women with ovarian cancer: no testing (reference); only if personal history of breast cancer, family history of breast/ovarian cancer, or Ashkenazi Jewish ancestry; only if invasive serous cancer; any invasive nonmucinous epithelial cancer. Net health benefit was life expectancy for FDRs and primary outcome was the incremental cost-effectiveness ratio (ICER). The model estimated the number of future breast and ovarian cancer cases in FDRs.BRCA testing based on personal/family history and ancestry could prevent future cases in FDRs with an ICER of $32,018 per year of life (LY) gained compared with the reference strategy. BRCA testing based on serous or any nonmucinous epithelial ovarian cancer could prevent more cancer cases, but at ICERs of $128,465 and $148,363 per LY gained, respectively.BRCA testing of women with ovarian cancer based on personal/family history of cancer or Ashkenazi Jewish ancestry is a cost-effective strategy to prevent future breast and ovarian cancers among FDRs. More inclusive testing strategies prevent additional cancer cases but at significant cost.
Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance
Authors: Masashi Yano, Noriyuki Kuroda, Hongwei Han, Makiko Meguro-Horike, Yumiko Nishikawa, Hiroshi Kiyonari, Kentaro Maemura, Yuchio Yanagawa, Kunihiko Obata, Satoru Takahashi, Tomokatsu Ikawa, Rumi Satoh, Hiroshi Kawamoto, Yasuhiro Mouri, Mitsuru Matsumoto
Journal: The Journal of Experimental Medicine (2008)

The roles of autoimmune regulator (Aire) in the expression of the diverse arrays of tissue-restricted antigen (TRA) genes from thymic epithelial cells in the medulla (medullary thymic epithelial cells [mTECs]) and in organization of the thymic microenvironment are enigmatic. We approached this issue by creating a mouse strain in which the coding sequence of green fluorescent protein (GFP) was inserted into the Aire locus in a manner allowing concomitant disruption of functional Aire protein expression. We found that Aire(+) (i.e., GFP(+)) mTECs were the major cell types responsible for the expression of Aire-dependent TRA genes such as insulin 2 and salivary protein 1, whereas Aire-independent TRA genes such as C-reactive protein and glutamate decarboxylase 67 were expressed from both Aire(+) and Aire(-) mTECs. Remarkably, absence of Aire from mTECs caused morphological changes together with altered distribution of mTECs committed to Aire expression. Furthermore, we found that the numbers of mTECs that express involucrin, a marker for terminal epidermal differentiation, were reduced in Aire-deficient mouse thymus, which was associated with nearly an absence of Hassall's corpuscle-like structures in the medulla. Our results suggest that Aire controls the differentiation program of mTECs, thereby organizing the global mTEC integrity that enables TRA expression from terminally differentiated mTECs in the thymic microenvironment.
Retinoic acid controls the homeostasis of pre-cDC–derived splenic and intestinal dendritic cells
Authors: Christopher A. Klebanoff, Sean P. Spencer, Parizad Torabi-Parizi, John R. Grainger, Rahul Roychoudhuri, Yun Ji, Madhusudhanan Sukumar, Pawel Muranski, Christopher D. Scott, Jason A. Hall, Gabriela A. Ferreyra, Anthony J. Leonardi, Zachary A. Borman, Jinshan Wang, Douglas C. Palmer, Christoph Wilhelm, Rongman Cai, Junfeng Sun, Joseph L. Napoli, Robert L. Danner, Luca Gattinoni, Yasmine Belkaid, Nicholas P. Restifo
Journal: The Journal of Experimental Medicine (2013)

Dendritic cells (DCs) comprise distinct populations with specialized immune-regulatory functions. However, the environmental factors that determine the differentiation of these subsets remain poorly defined. Here, we report that retinoic acid (RA), a vitamin A derivative, controls the homeostasis of pre-DC (precursor of DC)–derived splenic CD11b+CD8α−Esamhigh DCs and the developmentally related CD11b+CD103+ subset within the gut. Whereas mice deprived of RA signaling significantly lost both of these populations, neither pre-DC–derived CD11b−CD8α+ and CD11b−CD103+ nor monocyte-derived CD11b+CD8α−Esamlow or CD11b+CD103− DC populations were deficient. In fate-tracking experiments, transfer of pre-DCs into RA-supplemented hosts resulted in near complete conversion of these cells into the CD11b+CD8α− subset, whereas transfer into vitamin A–deficient (VAD) hosts caused diversion to the CD11b−CD8α+ lineage. As vitamin A is an essential nutrient, we evaluated retinoid levels in mice and humans after radiation-induced mucosal injury and found this conditioning led to an acute VAD state. Consequently, radiation led to a selective loss of both RA-dependent DC subsets and impaired class II–restricted auto and antitumor immunity that could be rescued by supplemental RA. These findings establish a critical role for RA in regulating the homeostasis of pre-DC–derived DC subsets and have implications for the management of patients with immune deficiencies resulting from malnutrition and irradiation.
THE AETIOLOGY OF HEART DISEASE
Authors: C. B. Perry
Journal: BMJ (1934)

JOURINALhouse, this would suggest that in the smaller type of house girls are more liable to infection than boys, while the reverse is the case in the larger houses.TABLE V.-Size of House and Sex Incidence inz Children C7 { I III IV Over IV Percentage number of 7.8 53.3 20.1 8.0 10.8 boy-s Percenitage number of 8.5 57.2 18 0 7.8 8.5 girls VARIATI,ON OF INCIDENCE WITH SEX AND AGETABLE VI.-Sex and Age I1ncidence I ;1 *F gl ol fl $ gl gl g! uo o c c| 0 P-.0 o oZolio °E °E °E .E+ °c,e cd Cl 'r Ca e £z!d T, Ca r £rr.ce X C dC c. irCa S a) Q4 p, -4.1 >_ oH i5 IO .
Lifestyle Intervention for Prevention of Type 2 Diabetes in Primary Health Care
Authors: Timo Saaristo, Leena Moilanen, Eeva Korpi-Hyövälti, Mauno Vanhala, Juha Saltevo, Leo Niskanen, Jari Jokelainen, Markku Peltonen, Heikki Oksa, Jaakko Tuomilehto, Matti Uusitupa, Sirkka Keinänen-Kiukaanniemi
Journal: Diabetes Care (2010)

OBJECTIVE To investigate 1-year outcomes of a national diabetes prevention program in Finland. RESEARCH DESIGN AND METHODS Altogether 10,149 individuals at high risk for diabetes were identified with the Finnish Diabetes Risk Score (FINDRISC; scoring ≥15 points), by a history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), cardiovascular disease, or gestational diabetes mellitus in 400 primary health care centers. One-year follow-up data were available for 2,798 participants who were nondiabetic at baseline (919 men and 1,879 women, aged 56.0 ± 9.9 and 54.0 ± 10.7 years [mean ± SD] with BMI 30.9 ± 4.6 and 31.6 ± 5.4 kg/m2). RESULTS The incidence of diabetes was 2.0 and 1.2% in men and women with normal glucose tolerance at baseline, 13.5 and 7.4% in those with IFG, and 16.1 and 11.3% in those with IGT, respectively. Altogether 17.5% of the subjects lost ≥5% weight with no sex difference. The relative risk of diabetes was 0.31 (95% CI 0.16–0.59) in the group who lost ≥5% weight, 0.72 (0.46–1.13) in the group who lost 2.5–4.9% weight, and 1.10 (0.77–1.58) in the group who gained ≥2.5% compared with the group who maintained weight. CONCLUSIONS The FIN-D2D was the first national effort to implement the prevention of diabetes in a primary health care setting. Methods for recruiting high-risk subjects were simple and easy to use. Moderate weight loss in this very high-risk group was especially effective in reducing risk of diabetes among those participating in the program.
Asthma mortality in Danish children and young adults, 1973-1994: epidemiology and validity of death certificates
Authors: I.M Jorgensen, S Bulow, V.B Jensen, T.L Dahm, P Prahl, K Juel
Journal: European Respiratory Journal (2000)

Several reports indicate that asthma mortality has increased during the last few decades. International comparisons reveal some striking differences in the pattern of asthma mortality. The authors investigated the asthma mortality rate in the Danish child and youth population 1973-1994 and studied the validity of death certificates. The authors reviewed all death certificates coded as asthma death in the International Classification of Diseases (ICD 8-ICD 10 (1994)) and adjacent respiratory code numbers for the age group 1-19 yrs. Hospital records and autopsy reports were assessed to validate the cause of death. Age-standardized and age-specific mortality rates were calculated. From 1973 to 1987 there was a significant upward trend in the mortality. On subdivision, this trend was limited to the age group 15-19 yrs. Generally the mortality rate decreased from 1988 to 1994. Four per cent coded as asthma were false positive. Twelve per cent were false negative asthma deaths, wrongly coded as due to other causes. Only 62% of all true positive death caused by asthma were appropriately coded. The number of false negative certifications increased with increasing autopsy frequency. Asthma mortality rates in Denmark increased in adolescents during 1973-1987 and decreased from 1988 to 1994. A possible explanation may be an increased awareness of asthma symptoms combined with a steadily improved treatment of asthma. Even in children and young adults under the age of 20 yrs, validity problems still make comparisons between countries difficult; even interpretation of national trends requires caution.
Acetazolamide for Monge's Disease
Authors: Jean-Paul Richalet, Maria Rivera-Ch, Maxime Maignan, Catherine Privat, Isabelle Pham, Jose-Luis Macarlupu, Olivier Petitjean, Fabiola León-Velarde
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Monge's disease is characterized by an excessive erythrocytosis, frequently associated with pulmonary hypertension, in high-altitude dwellers. It has a considerable impact on public health in high-altitude regions. A preliminary study demonstrated the efficiency of acetazolamide (Acz) (250 mg/d for 3 wk) in reducing serum erythropoietin and hematocrit.Objectives: Evaluate the efficacy and tolerance of a 6-month treatment with 250 mg Acz that could be chronically implemented and its effects on pulmonary artery pressure and cardiac function.Methods: A two-phase study was performed in patients (hematocrit ⩾ 63%) from Cerro de Pasco, Peru (4,300 m). First phase: a double-blind, placebo-controlled study in 55 patients who received a single dose of either 250 mg Acz (n = 40) or placebo (n = 15) by daily oral administration for 12 weeks. Second phase (open label): after a 4-week washout period, all patients received 250 mg Acz for 12 weeks. Hematocrit, blood gases, clinical outcome, and pulmonary artery circulation were evaluated.Measurements and Main Results: First phase: Acz decreased by 44% the number of polycythemic subjects (P = 0.02), decreased hematocrit from 69 to 64% (P < 0.001), and increased arterial O2 pressure from 42 to 45 mm Hg (P < 0.001). No severe adverse effect or hypokalemia was recorded. The second phase reproduced the effects observed during the first phase, without cumulative effects on hematocrit. A 4-week washout restored basal hematocrit. Only patients who received Acz for 6 months showed a clear reduction in pulmonary vascular resistance.Conclusions: Acz reduces erythrocytosis and improves pulmonary circulation in Monge's disease without adverse effects. Its implementation as a chronic treatment for this disease appears efficient and safe.Clinical trial registered with www.clinicaltrials.gov (NCT 00424970).
Microsatellite Size Homoplasy, SSCP, and Population Structure: A Case Study in the Freshwater Snail Bulinus truncatus
Authors: B. Angers, A. Estoup, P. Jarne
Journal: Molecular Biology and Evolution (2000)

The extent of microsatellite size homoplasy, as well as its effect on several population genetics statistics, was investigated in natural populations using the single-strand conformation polymorphism (SSCP) method. The analysis was conducted using 240 individuals from 13 populations of the freshwater snail Bulinus truncatus at a GTnCTm compound microsatellite locus. We showed that SSCP can be used to uncover, at least partly, size homoplasy in the core sequence of this category of loci. Eight conformers (SSCP variants) were detected among the three size variants (electromorphs). Sequencing revealed that each conformer corresponded to a different combination of repeats in the GTn and CTm arrays. Part of this additional variability was detected within populations, resulting in a substantial increase in gene diversity in four populations. Additional variability also changed the values of parameters used to analyze population differentiation among populations: pairwise tests of differentiation were significant much more often with conformers than with electromorphs. On the other hand, pairwise estimates of Fst were either smaller or larger with conformers than with electromorphs, depending on whether or not electromorphs were shared among populations. However, estimates of Fst (or analogs) over all populations were very similar, ranging between 0.66 and 0.75. Our results were consistent with the theoretical prediction that homoplasy should not always lead to stronger population structure. Finally, conformer sequences and electromorph size distribution suggested that single-point and/or stepwise mutations occurring simultaneously in the different repeated arrays of compound microsatellites produce sequence variation without size variation and hence generate more size homoplasy than expected under a simple stepwise mutation model.
Pathobiont hypnotises enterocytes to promote tumour development
Authors: Benoit Chassaing, Andrew T Gewirtz
Journal: Gut (2014)

The relative contribution of thromboxane (TX)A2/prostaglandin (PG)H2 and ADP to platelet shape change was determined using the specific TXA2/PGH2 antagonist, 13-azaprostanoic acid (13-APA) and the ADP antagonist, ATP. Shape change was induced in human platelet-rich plasma with doses of arachidonic acid (AA) or the PG endoperoxide analog U46619, which did not cause measurable ATP/ADP release. Pretreatment of platelet-rich plasma with 13-APA completely inhibited shape change to AA or U46619 but did not inhibit ADP-induced shape change. In contrast, ATP completely blocked shape change to ADP but not to AA or U46619. In addition, 13-APA and ATP also selectively reversed shape change. Thus, 13-APA added 1.5 min subsequent to AA or U46619 resulted in almost complete reversal of the shape change response. However, 13-APA did not reverse ADP-induced shape change. A similar selectivity was observed with ATP which reversed shape change to ADP but not to AA or U46619. These findings provide evidence that the interaction of TXA2/PGH2 with its receptor results in the direct stimulation of shape change independent of secreted ADP. Furthermore, maintenance of this shape change response appears to require continued occupation of the TXA2/PGH2 receptor.
Plugging the Posterior Nares in Cases of Persistent Epistaxis
Authors: J. I. Mackenzie
Journal: BMJ (1868)

XSS.TAM BRIShF MfED CAL 7OURWAL.s15 and sy that they ol difer in the atcks beig multiple, and in the ancsms ad wb they o .Neiiher of these features seem to me to establish any material distinction between the two classes.Multiple attacks ae, we well know, met with every now and then in cronsc epilepsy.As to,the attendat and originating circumstances, chen the iblC result s so simila, it seems to me very much like ng the uestion at ine, to afirm that the condition of brain they prbdce is ulike that which preils in all cases of essential epilepsy.
Evolutionary rates of insertion and deletion in noncoding nucleotide sequences of primates.
Authors: N Saitou, S Ueda
Journal: Molecular Biology and Evolution (1994)

Insertions and deletions are responsible for gaps in aligned nucleotide sequences, but they have been usually ignored when the number of nucleotide substitutions was estimated. We compared six sets of nuclear and mitochondrial noncoding DNA sequences of primates and obtained the estimates of the evolutionary rate of insertion and deletion. The maximum-parsimony principle was applied to locate insertions and deletions on a given phylogenetic tree. Deletions were about twice as frequent as insertions for nuclear DNA, and single-nucleotide insertions and deletions were the most frequent in all events. The rate of insertion and deletion was found to be rather constant among branches of the phylogenetic tree, and the rate (approximately 2.0/kb/Myr) for mitochondrial DNA was found to be much higher than that (approximately 0.2/kb/Myr) for nuclear DNA. The rates of nucleotide substitution were about 10 times higher than the rate of insertion and deletion for both nuclear and mitochondrial DNA.
Lack of association between hepatotropic transfusion transmitted virus infection and oral lichen planus in British and Italian populations.
Authors: C. Bez, R. Hallett, M. Carrozzo, G. Lodi, S. Gandolfo, A. Carrassi, C. Scully, S.R. Porter
Journal: British Journal of Dermatology (2001)

A possible association between oral lichen planus (OLP) and chronic hepatic disease has been found in some populations, although this is probably geographically influenced. In 1997 a new hepatotropic virus, transfusion transmitted virus (TTV), was identified but has not been studied in relation to OLP.The present investigation evaluated the genoprevalence of TTV DNA in the sera of British and Italian patients suffering from OLP using two different sets of primers to identify TTV subgenomic DNA.Study groups comprised 40 adult subjects (21 British, 19 Italian) with OLP. For each country, two control groups, a disease-control group and a healthy-control group, were included. The presence of TTV DNA in the sera of patients and control subjects was assessed using two different polymerase chain reactions (PCR) and DNA sequence analysis.Statistical analysis did not reveal evidence of any association between TTV infection and OLP or country of residence.An association between TTV and OLP is unlikely.
Endurance in sport, 2nd edn.: Edited by R J Shephard, P O Astrand. Blackwell Science, Oxford, 2000, pound85.00, pp 987. ISBN 0632053488
Authors: K Fallon
Journal: British Journal of Sports Medicine (2002)

Generally when faced with encyclopaedic texts, I become fearful of superficial coverage of a wide variety of subjects with which I soon lose interest. Happily I can report that this volume, of almost 1000 pages, maintained my interest in chapters about which I had some knowledge and stimulated interest in areas about which I knew little.

As may be expected, the range of subjects is enormous and can best be described as falling into the following areas which are, indeed, …
GPs must see NICE guidance as relevant and essential, says potential new NICE chairman
Authors: A. O'Dowd
Journal: BMJ (2012)

Steps must be taken to convince GPs that guidance from the UK National Institute for Health and Clinical Excellence (NICE) is relevant and useful to them, MPs have been told.

The man likely to be the new chairman of the NHS’s drug watchdog has outlined plans to ensure that NICE produces guidance in the future that is more relevant to GPs.

David Haslam, former president and chairman of the Royal College of General Practitioners, a GP in Cambridgeshire until last year, and a past BMA president, appeared before the parliamentary health select committee on 11 December.

The committee was holding a pre-appointment scrutiny hearing, after Haslam was nominated as …
Chronic Lymphocytic Leukemia Is Associated With Decreased Survival of Patients With Malignant Melanoma and Merkel Cell Carcinoma in a SEER Population-Based Study
Authors: Jerry D. Brewer, Tait D. Shanafelt, Clark C. Otley, Randall K. Roenigk, James R. Cerhan, Neil E. Kay, Amy L. Weaver, Timothy G. Call
Journal: Journal of Clinical Oncology (2012)

To delineate outcomes of malignant melanoma (MM) and Merkel cell carcinoma (MCC) in patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin's lymphoma (NHL).We identified patients with MM or MCC reported to the Surveillance, Epidemiology, and End Results program and analyzed the effects of history of CLL/NHL on overall (OS) and cause-specific survival after MM or MCC. Expected survival was derived from patients with MM or MCC without CLL/NHL.From 1990 to 2006, 212,245 patients with MM and 3,613 patients with MCC were identified, of whom 1,246 with MM and 90 with MCC had a prior diagnosis of CLL/NHL. Patients with MM and a history of CLL/NHL had worse-than-expected OS as measured by standardized mortality ratio (SMR; SMR for CLL, 2.6; 95% CI, 2.3 to 3.0; SMR for NHL, 2.3; 95% CI, 2.1 to 2.6). MM cause-specific survival was worse than expected for patients with a history of CLL (SMR, 2.8; 95% CI, 2.2 to 3.4) or NHL (SMR, 2.1; 95% CI, 1.7 to 2.6). Among patients with MCC, OS was worse than expected for those with a history of CLL (SMR, 3.1; 95% CI, 2.2 to 4.3) or NHL (SMR, 1.9; 95% CI, 1.3 to 2.8). MCC cause-specific survival was worse than expected for patients with a history of CLL (SMR, 3.8; 95% CI, 2.5 to 5.9), but no difference was observed for NHL (SMR, 0.9; 95% CI, 0.4 to 2.1).Patients with CLL before diagnosis of MM or MCC have significantly worse OS and MM or MCC cause-specific survival than those without a history of CLL/NHL.