tbuckley/cabot-search huggingface dataset:
Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in taiwan
Authors: Hong-Yuan Hsu, Mei-Hwei Chang, Shwu-Huey Liaw, Yen-Hsuan Ni, Huey-Ling Chen
Journal: Hepatology (1999)

Mutants of a determinant of hepatitis B surface antigen (HBsAg) identified in vaccinated children pose a potential threat to long-term success of vaccination programs. We examined the mutants of a determinant (residues 110-160) of HBsAg in hepatitis B virus (HBV) DNA-positive children identified during previous serosurveys in Taipei undertaken just before (1984), 5 years after (1989), and 10 years after (1994) universal vaccination began. In HBV DNA-positive children from 3 surveys, the prevalence of a determinant mutants increased from 8 of 103 (7.8%) in 1984 to 10 of 51(19.6%) in 1989 and 9 of 32 (28.1%) in 1994 and was higher in those fully-vaccinated than unvaccinated (12/33 vs. 15/153, P = .0003). Most amino acid changes of the variants clustered in residues 125-129 and 140-149. In all 27 children with detectable mutants, the mean age of those vaccinated was younger than those unvaccinated (4.8 ± 3.8 vs. 7.9 ± 2.3 yrs, P &lt; .05); and mutations occurred in a region with greatest local hydrophilicity (residues 140-149) more frequently in those vaccinated than in those unvaccinated (10/12 vs. 6/15, P = .0253). More mutated residues and more mutations at neutralizing epitopes, such as N146, C147, T148, and C149, were found in the 1994 survey. Vaccinated children may contract variant infections through vertical or horizontal transmission. Universal vaccination has accelerated an accumulation of HBsAg a determinant mutants with amino acid changes critical for immune escape in vaccinated children who became carriers, suggesting that new vaccination strategies should be considered.
THE P53 PATHWAY AND ANCESTRAL PROGENITORS ARE ASSOCIATED WITH TUMOR RECURRENCE IN GLIOBLASTOMA
Authors: R. G. W. Verhaak, H. Kim, S. Zheng, S. S. Amini, S. M. Virk, T. Mikkelsen, D. J. Brat, J. Grimsby, C. Sougnez, F. Muller, J. Hu, A. E. Sloan, M. L. Cohen, E. G. Van Meir, L. Scarpace, P. W. Laird, J. N. Weinstein, E. Lander, S. Gabriel, G. Getz, M. Meyerson, L. Chin, J. S. Barnholtz-Sloan
Journal: Neuro-Oncology (2014)

BACKGROUND: The mechanisms driving glioblastoma (GBM) relapse remain elusive. To investigate evolutionary patterns in recurrence and therapy-resistance of GBM, we analyzed the genomic profiles from 252 primary GBM and 60 biopsy samples taken from 23 pairs of pre- and post-treatment GBM tumors. METHODS: We integrated mutation allele fraction, DNA copy number and genotype information to determine the cellular frequencies of all mutations and found that 70.5% of mutations were classified as clonal and 30.5% as subclonal. We validated our classification approach through multi-sector sequencing of 13 GBM tumors. RESULTS: Separating patients into discrete age groups by an interval of 10 years, we observed a significant linear correlation between clonal mutations and age (P < 3.69x10−7), but no correlation between age and subclonal mutations (P = 0.62). This result suggested that clonal mutations predominantly accumulated over the life span of the cell population that gave rise to the cell of origin before neoplastic onset, whereas_ENREF_22 subclonal mutations were acquired during tumorigenesis and may reflect intratumor heterogeneity. Interestingly, mutation or aneuploidy of p53 pathway members strongly correlated with increased fraction of subclonal mutations (P = 6 × 10−5, Wilcoxon rank test), unrelated to patient age. To further evaluate the association between TP53 mutation status, intratumoral heterogeneity and clonal evolution, we analyzed exome sequencing and DNA copy number data from 23 pairs of first and recurrent GBM tumors. We found that TP53 mutant GBM showed a significant increase in subclonal mutation frequency relative to the matched primary tumor (P = 0.0015). The clonal mutation frequency was unaffected (P = 0.23). These data suggested that TP53 mutant GBM became increasingly clonally complex at time of recurrence, whereas TP53 wildtype GBM showed a reduced level of intratumoral heterogeneity. To comprehensively investigate tumor recurrence we performed whole genome sequencing of seven primary-recurrent tumor pairs. We found that major clones in the tumor recurrence resembled major clones in the matching primary, and were both derived from an ancestral cell population. The same applied to minor clones, suggesting that multiple types of ancestral cells existed. CONCLUSIONS: We showed that mutations in the p53 pathway resulted in increased intratumoral heterogeneity at time of diagnosis and after tumor recurrence. Disease relapse was fueled by ancestral cell populations. Further research is needed to determine the impact of intratumoral heterogeneity on treatment response. Our study provides a molecular snapshot of tumor evolution in glioblastoma. SECONDARY CATEGORY: Neuropathology and Tumor Biomarkers.
Studies Examine Inflammatory Biomarker in Prevention and Prediction of Heart Disease
Authors: Mike Mitka
Journal: JAMA (2009)

NEW ORLEANS—Researchers have demonstrated that a new primary prevention strategy may reduce cardiovascular events in certain patients at risk of cardiovascular disease. At the Scientific Sessions of the American Heart Association (AHA) held here in November, scientists reported that among apparently healthy patients with elevated levels of high-sensitivity Creactive protein (hsCRP, an inflammatory biomarker) but without elevated low-density lipoprotein cholesterol (LDL-C) levels ( 130 mg/dL), using a statin reduced the LDL-C levels and significantly reduced the risk of myocardial infarction, stroke, and death. In addition, findings from other studies presented at the meeting suggested that hsCRP may improve cardiovascular risk stratification beyond such traditional factors as age, blood pressure, total cholesterol, smoking status, and diabetes mellitus. These results about the potential utility of hsCRP in risk assessment most likely will be considered in updates of guidelines for the assessment and management of cardiovascular risk factors. Committees writing such updates are already convening and are expected to publish their revisions in early 2010.
How to meet the challenge of ageing populations
Authors: N. Fahy, M. McKee, R. Busse, E. Grundy
Journal: BMJ (2011)

EU countries need to work together with health professionals and other stakeholders



The EU partnership aims to add two years of healthy life to the European average by 2020



One of the main arguments used to justify major reform of the NHS is the potential cost of an ageing population. The United Kingdom is not alone; the number of people aged over 65 in the European Union will almost double over the next 50 years,1 and there will be only two people of “working age” for each person over 65 compared with four today. It is estimated that this could cost EU countries as much as 15-40% on top of current expenditure to maintain existing health services. So how is Europe collectively responding?

EU leaders (including those from the UK) are pinning much hope on “innovation”—speeding up the process of bringing new ideas from research to practical application.2 As part of this “innovation union” initiative, the European Commission has proposed a “pilot partnership on active and healthy ageing.”3 By bringing together government officials, industry, health professionals, and other stakeholders from across Europe, the commission hopes to find …
THE TREATMENT OF UTERINE FIBROIDS BY MYOMECTOMY
Authors: P. L. Giuseppi
Journal: BMJ (1925)

CHARLES DAV~ID) in a Paris thiesis (1908), described a method of endoscopy of the uterus, in which he employed an instrument consisting of a sheath into which fitted the cystoscope, closed at the far end by a glass crystal and coiltaining near it an incandescent lamp.By enclosing
444 SVR FOR CONTROLLED-RELEASE INTERFERON ALPHA-2B (CR2B) +RIBAVIRIN COMPARED TO PEGYLATED INTERFERON ALPHA-2B (PEG2B) +RIBAVIRIN IN TREATMENT-NAIVE GENOTYPE-1 (G1) HEPATITIS C: FINAL RESULTS FROM SELECT-2
Authors: E. Lawitz, Z. Younossi, R. Mehra, A. Rigney, Z. Krastev, K. Tchernev, D. Takov, W.A. Long
Journal: Journal of Hepatology (2011)
Legionnaire's Disease
Authors: William R. Barclay
Journal: JAMA (1978)

Description of a new infectious disease is now a rare event. When such a disease is discovered and when it is of relatively common occurrence, it justifiably generates both excitement and interest within the medical profession. Legionnaire's disease was not only newly recognized in 1976, it also presented on the medical horizon in a dramatic fashion. Although the clinical features and the epidemic nature of the outbreaks left no doubt that we were witnessing a specific clinical entity, it was almost a year and a half before the specific agent, a Gram-negative bacterium, was identified and isolated.  Following the initial outbreak of cases in Philadelphia in the summer of 1976, sporadic outbreaks occurred in other parts of the country. Identification of cases of Legionnaire's disease has been considerably simplified by the development of an indirect immunofluorescence test for a rise in specific serum antibodies. A specific diagnosis can also be
Lymphocyte subpopulation abnormalities in sickle cell anemia: A distinctive pattern from that of AIDS
Authors: Oscar F. Ballester, Jorge M. Abdallah, Ananda S. Prasad
Journal: American Journal of Hematology (1986)

Abstract In this study, we evaluated lymphocyte subpopulations in 23 adults with SCA. When compared to controls, SCA patients had higher lymphocyte counts with normal numbers of T101+ cells (T‐lymphocytes) and T4 + cells. T8+ cells were significantly increased in SCA patients in comparison to controls (1684 ± 243 vs 980 ± 367, p &lt; .001). This increment was largely dependent on a T101 ‐, T8+ cell population. The SCA patients as a group had significantly decreased T4/T8 ratio (p &lt; .0001). The SCA patients with history of blood transfusions had higher T4+ cells numbers and higher T4/T8 ratio, but no other significant differences from nontransfused patients were noted. Our results are different from those reported for nontransfused children with SCA who showed normal T4/T8 ratio. Thus, a distinct pattern of abnormalities is seen in the lymphocyte subpopulations of adult SCA patients, unrelated to their exposure to blood transfusions.
Adding metformin to insulin did not improve a composite of microvascular and macrovascular disease in type 2 diabetes
Authors: Vivian Fonseca
Journal: Annals of Internal Medicine (2009)

Source Citation Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med. 2009;169:616-25. 19307526
More pain, more tender points: is fibromyalgia just one end of a continuous spectrum?
Authors: P Croft, J Burt, J Schollum, E Thomas, G Macfarlane, A Silman
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVES: To investigate the hypothesis that fibromyalgia represents one end of a spectrum in which there is a more general association between musculoskeletal pain and tender points. METHODS: The subjects studied were 177 individuals selected from a population based screening survey for musculoskeletal pain. All subjects completed a pain mannikin and were examined for the presence of tender points at the nine American College of Rheumatology bilateral sites. RESULTS: There were moderately strong associations (odds ratios range 1.3-3.1) between the reported presence of pain in a body segment and the presence of a tender point within that segment. Further, there was evidence of a trend of increasing number of tender points with increasing number of painful segments. The reporting of non-specific pain, aching, or stiffness, was also associated with high tender point counts. CONCLUSION: This study illustrates that the association between tender points and pain is not restricted to the clinically defined subgroup with chronic widespread pain. Given that widespread pain and tender points have previously been linked with distress, this might reflect lesser degrees, or earlier phases of the somatisation of distress.
Inflammation, atrophy, and gastric cancer
Authors: James G. Fox, Timothy C. Wang
Journal: Journal of Clinical Investigation (2007)

The association between chronic inflammation and cancer is now well established. This association has recently received renewed interest with the recognition that microbial pathogens can be responsible for the chronic inflammation observed in many cancers, particularly those originating in the gastrointestinal system. A prime example is Helicobacter pylori, which infects 50% of the world’s population and is now known to be responsible for inducing chronic gastric inflammation that progresses to atrophy, metaplasia, dysplasia, and gastric cancer. This Review provides an overview of recent progress in elucidating the bacterial properties responsible for colonization of the stomach, persistence in the stomach, and triggering of inflammation, as well as the host factors that have a role in determining whether gastritis progresses to gastric cancer. We also discuss how the increased understanding of the relationship between inflammation and gastric cancer still leaves many questions unanswered regarding recommendations for prevention and treatment.
Donors raise 3.2bn for free health care in world's poorest countries
Authors: P. Moszynski
Journal: BMJ (2009)

A £3.2bn (€3.5bn; $5.1bn) funding initiative to expand free health care and improve maternal health was launched at the United Nations General Assembly in New York on 23 September.

Behind the initiative is the UN taskforce on innovative international financing for health systems, which is chaired by the UK prime minister, Gordon Brown, and president of the World Bank, Robert Zoellick. It will focus on “finding innovative financing mechanisms to strengthen health systems in the poorest countries in the world.”

Announcing the taskforce’s proposals, Mr Brown said: “We cannot let mothers and children die through lack of finance and through the persistence of user fees.” The £3.2bn raised …
Breast-Conserving Surgery and Radiation Therapy: Are They Underused?
Authors: Michael G. Sarr, John H. Donohue, Clive S. Grant, Jon A. van Heerden, Donald C. McIlrath
Journal: JAMA (1992)

<h3>To the Editor.</h3> —We have three objections to the article by Lazovich and colleagues.<sup>1</sup>Our first concern is the title that suggests that general surgeons "underutilize" conservative breast surgery and "mistreat" many women. The implication is that general surgeons should advise the use of breast-preserving surgery as opposed to mastectomy for the majority of patients with breast cancer. No mention is made of the inconvenience of 5 to 6 weeks of irradiation for a woman who lives a long distance from a qualified treatment center. Breast irradiation is time-consuming and expensive (as suggested in the article); many women have fears of recurrence in the preserved breast. These factors are downplayed, minimized, or ignored in the design, data acquisition, and discussion of the article by Lazovich et al. Many of our patients choose not to pursue adjuvant radiotherapy. Many view mastectomy as dealing with the problem immediately and completely, without
Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation.
Authors: C Chen, L Rodriguez, R A Levine, A E Weyman, J D Thomas
Journal: Circulation (1992)

BACKGROUND The time constant of isovolumic relaxation (tau) is an important parameter of ventricular diastolic function, but the need for invasive measurement with high-fidelity catheters has limited its use in general clinical cardiology. The Doppler mitral regurgitant velocity spectrum can be used to estimate left ventricular (LV) pressure throughout systole and may provide a new noninvasive method for estimating tau. METHODS AND RESULTS Mitral regurgitation was produced in nine dogs, and ventricular relaxation was adjusted pharmacologically and with hypothermia. High-fidelity ventricular pressures were recorded, and tau was calculated from these hemodynamic data (tau H) assuming a zero-pressure asymptote. Continuous-wave mitral regurgitant velocity profiles were obtained, and the ventriculo-atrial (VA) pressure gradient was calculated by the simplified Bernoulli equation; tau was calculated from the Doppler data from the time of maximal negative dP/dt until LV-LA pressure crossover. Three methods were used to correct the Doppler VA gradient to better approximate the LV pressure before calculating tau: 1) adding actual LA V wave pressure (to yield tau LA); 2) adding 10 mm Hg (tau 10); and 3) no adjustment at all (actual VA gradient used to calculate tau 0). The agreement between tau H and the three Doppler estimates of tau was assessed by linear regression and by the mean and standard deviation of the error between the measurements (delta tau). the measurements (delta tau). tau H ranged from 29 to 135 msec. Without correction for LA pressure, the Doppler estimate of tau seriously underestimated tau H: tau 0 = 0.30 tau H + 9.4, r = 0.79, delta tau = -35 +/- 18 msec. This error was almost completely eliminated by adding actual LA pressure to the VA pressure gradient: tau LA = 0.92 tau H + 7.6, r = 0.95, delta tau = 2 +/- 7 msec. Addition of a fixed LA pressure estimate of 10 mm Hg to the VA gradient yielded an estimate that was almost as good: tau 10 = 0.89 tau H + 4.9, r = 0.88, delta tau = -2 +/- 12 msec. In general, tau was overestimated when actual LA pressure was below this assumed value, and vice versa. Numerical analysis demonstrated that assuming LA pressure to be 10 mm Hg should yield estimates of tau accurate to +/- 15% between true LA pressures of 5 and 20 mm Hg. CONCLUSIONS This study demonstrates that the Doppler mitral regurgitant velocity profile can be used to provide a direct and noninvasive measurement of tau. Because mitral regurgitation is very common in cardiac patients, this method may allow more routine assessment of tau in clinical and research settings, leading to a better understanding of the role of impaired ventricular relaxation in diastolic dysfunction and the effect of therapeutic interventions.
TCT-887 TAVR– 3 year results of transapical versus transfemoral approach in a real world population of 1000 patients with severe aortic stenosis
Authors: G. Schymik, T. Herbinger, A. Wuerth, J.-S. Schymik, P. Bramlage, M. Heimeshoff, T. Sueselbeck, R. Kiefer, B.-D. Gonska, H. Posival, C. Schmitt, H. Schroefel
Journal: Journal of the American College of Cardiology (2012)
Advanced Dermatologic Diagnosis
Authors: William P. Coleman
Journal: JAMA (1993)

One night 20 years ago, when I was still trying to decide whether or not to study dermatology, I read a book entitled<i>Consultations in Dermatology</i>by Dr Walter Shelley. His writing and his breadth of knowledge made dermatology come alive for me. Reading his book was pivotal in my decision to choose a dermatology residency. Since then I have always been enthralled by the writings of Dr Shelley and more recently by his collaborations with his wife Dorinda. Their prose is a perfect blend of Arthur Conan Doyle and James Thurber. This is not the usual stuffy language of medical literature but a seductive dialogue, which draws the reader into the Shelleys' fascination with the intriguing world of dermatology. Their newest book,<i>Advanced Dermatologic Diagnosis</i>, is their finest effort to date. It is difficult to believe that a 1300-page textbook is as hard to put down as a fine
Research progress in the phytochemistry and biology of Ilex pharmaceutical resources
Authors: Dacheng Hao, Xiaojie Gu, Peigen Xiao, Zhanguo Liang, Lijia Xu, Yong Peng
Journal: Acta Pharmaceutica Sinica B (2013)

Ilex is a botanical source for various health-promoting and pharmaceutically active compounds that have been used in traditional Chinese medicine and food for thousands of years. Increasing interest in Ilex pharmaceutical and food resources has led to additional discoveries of terpenoids, saponins, polyphenols (especially flavonoids), glycosides, and many other compounds in various Ilex species, and to investigation of their chemotaxonomy, molecular phylogeny and pharmacology. In continuation of our studies on Ilex pharmacology and phylogeny, we review the phytochemistry, chemotaxonomy, molecular biology and phylogeny of Ilex species and their relevance to health-promotion and therapeutic efficacy. The similarity and dissimilarity between Ilex paraguariensis, the source plant of mate tea, and the source plants of large-leaved Kudingcha (e.g., Ilex kudingcha and Ilex latifolia) are discussed. It is essential to utilize emerging technologies in non-Camellia tea studies to promote the sustainable utilization of Ilex resources and the identification and development of novel compounds with potential health and clinical utility. Systems biology and "-omics" technologies will play an increasingly important role in pharmaceutical and food research on the bioactive compounds of Ilex species.
Demonstration of free radical generation in the "stunned" myocardium in the conscious dog and identification of major differences between conscious and open-chest dogs.
Authors: X Y Li, P B McCay, M Zughaib, M O Jeroudi, J F Triana, R Bolli
Journal: Journal of Clinical Investigation (1993)

Conscious dogs undergoing a 15-min coronary occlusion were given alpha-phenyl N-tert-butyl nitrone (PBN) and the local coronary venous plasma was analyzed by electron paramagnetic resonance spectroscopy. A prolonged myocardial release of PBN radical adducts was observed, which exhibited a burst in the initial minutes of reflow (peaking at 3 min) and then abated but continued for 1-3 h after reperfusion. Computer simulation revealed the presence of at least two PBN adducts (aN = 15.2 G and a beta H = 6.0 G; aN = 14.6 G and a beta H = 3.0 G), both consistent with the trapping of secondary carbon-centered radicals. No appreciable PBN adduct production was observed when collateral flow exceeded 30-40% of nonischemic flow, indicating that a flow reduction of at least 60% is necessary to trigger free radical reactions. There was a direct relationship between the magnitude of PBN adduct production and the severity of contractile dysfunction (r = 0.77), suggesting that the radicals generated upon reperfusion play a causal role in the subsequent stunning. The total release of PBN adducts after 3 h of reperfusion following a 15-min coronary occlusion was found to be approximately five times greater in open-chest compared with conscious dogs; at the same time, the recovery of wall thickening was markedly less in open-chest dogs. This study represents the first application of spin trapping to a conscious animal model of myocardial ischemia. The results demonstrate (a) that free radicals are generated in the stunned myocardium in the absence of the artificial or abnormal conditions associated with previously used models (isolated hearts, open-chest preparations), and (b) that both the severity of postischemic dysfunction and the magnitude of the attendant free radical production are greatly exaggerated in the open-chest dog, implying that previous conclusions derived from this model may not be applicable to conscious animals or to humans. This investigation also provides a method to measure free radicals in awake animals.