tbuckley/cabot-search huggingface dataset:
Dlastolic Pressure-Volume Relationship in the Canine Left Ventricle
Authors: George Diamond, James S. Forrester, James Hargis, William W. Parmley, Ronald Danzig, H. J. C. Swan
Journal: Circulation Research (1971)

Analysis of the passive pressure-volume filling curve of the left ventricle demonstrates that heart size and ventricular geometry exert major effects on the pressure-volume curve in the absence of changes in intrinsic muscle stiffness. Because the pressure-volume relationship is curvilinear, both quantitative and qualitative comparison of pressure-volume curves from different hearts is difficult. In the fresh isolated canine left ventricle, the pressure-volume relation was found to be almost perfectly exponential throughout a range of filling pressures from 5 to 30 mm Hg. Therefore, a precise linear and quantitative expression of the pressure-volume relation (dP/dV=aP+b) was developed (r=0.995). The effect of isolated changes in either initial ventricular volume (mean δa=3.1%) or ventricular geometry (mean δa=27.1%) upon the slope, or a constant of this function was small in comparison to changes induced by rigor mortis (mean δa =45%). It was concluded that the a constant was primarily affected by changes in left ventricular wall stiffness. In this manner, comparison of the pressure-volume relationship from different hearts is possible, and the contribution of changes in wall stiffness may be quantified.
Regulation of follicle development and novel approaches to ovarian stimulation for IVF
Authors: N. S. Macklon
Journal: Human Reproduction Update (2000)

Current ovarian stimulation regimens for IVF are complex and not without risk. Increasing our knowledge of the physiology of follicle development and dominant follicle selection may enable the design of less complex, safer and cheaper ovarian stimulation regimens for IVF. Decremental serum FSH concentrations during the follicular phase of the menstrual cycle are required for single dominant follicle selection. Only the most mature follicle will continue its development due to increased sensitivity for stimulation by FSH. FSH stimulation becomes insufficient for less mature follicles and remaining cohort follicles will therefore go into atresia. The number of days during which FSH is above the threshold for stimulation of follicle development is limited, resulting in a narrow FSH window. More medium sized and large pre-ovulatory follicles and increased oestradiol output can be induced by the administration of small doses of exogenous FSH during the mid- to late follicular phase, preventing the physiological decrease in FSH stimulation. Intervention with decremental serum FSH concentrations in combination with gonadotrophin-releasing hormone (GnRH) antagonists to prevent a premature rise in serum LH may induce ongoing growth of multiple follicles sufficient for IVF. The benefits and risks of these minimal hyperstimulation protocols require further evaluation.
Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study
Authors: Heather J Zar, Lesley Workman, Washiefa Isaacs, Keertan Dheda, Widaad Zemanay, Mark P Nicol
Journal: The Lancet Global Health (2013)

BackgroundIn children admitted to hospital, rapid, accurate diagnosis of pulmonary tuberculosis with the Xpert MTB/RIF assay is possible, but no paediatric studies have been done in the primary care setting, where most children are given care, and where microbiological diagnosis is rarely available. We assessed the diagnostic accuracy of Xpert MTB/RIF in children in primary care.MethodsFor this prospective study, we obtained repeat induced sputum and nasopharyngeal aspirate specimens from children (<15 years) with suspected pulmonary tuberculosis at a clinic in Khayeliwtsha, Cape Town, South Africa. We compared the diagnostic accuracy of Xpert MTB/RIF with a reference standard of culture and smear microscopy on induced sputum specimens. For the main analysis, specificity of Xpert MTB/RIF versus liquid culture, we included only children with two interpretable Xpert MTB/RIF and induced sputum culture results.FindingsBetween Aug 1, 2010, and July 30, 2012, we enrolled 384 children (median age 38·3 months, IQR 21·2–56·5) who had one paired induced sputum and nasopharyngeal specimen, 309 (81%) of whom had two paired specimens. Five children (1%) tested positive for tuberculosis by smear microscopy, 26 (7%) tested positive by Xpert MTB/RIF, and 30 (8%) tested positive by culture. Xpert MTB/RIF on two induced sputum specimens detected 16 of 28 culture-confirmed cases (sensitivity of 57·1%, 95% CI 39·1–73·5) and on two nasopharyngeal aspirates detected 11 of 28 culture-confirmed cases (sensitivity of 39·3, 23·6–57·6; p=0·18). The specificity of Xpert MTB/RIF on induced sputum was 98·9% (95% CI 96·9–99·6) and on nasopharyngeal aspirates was 99·3% (97·4–99·8).InterpretationOur findings suggest that Xpert MTB/RIF on respiratory secretions is a useful test for rapid diagnosis of paediatric pulmonary tuberculosis in primary care.FundingNational Institutes of Health, National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, the National Research Foundation South Africa, the European and Developing Countries Clinical Trials Partnership.
Different Activation of Mitogen-Activated Protein Kinase and Akt Signaling Is Associated with Aggressive Phenotype of Human Meningiomas
Authors: Christian Mawrin, Tina Sasse, Elmar Kirches, Siegfried Kropf, Thomas Schneider, Christoph Grimm, Claudia Pambor, Christian K. Vorwerk, Raimund Firsching, Uwe Lendeckel, Knut Dietzmann
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Activation of intracellular signaling cascades has been implicated in the growth control of benign meningiomas, but their role for meningioma progression and outcome is unknown. Here we determined the expression and function of proteins involved in mitogen-activated protein kinase (MAPK) and phosphinositol-3 kinase (PI3K)/Akt signaling in benign, atypical, and malignant meningiomas and studied their association with clinicopathologic data including meningioma recurrence. Experimental Design: Expression of various MAPK and PI3K signaling proteins was determined in 70 primary meningiomas and, if present, in recurrent tumors by immunohistochemistry and Western blotting. The expression patterns in primary and recurrent tumors were related to clinical data. The effect of MAPK and PI3K pathway inhibition on cell proliferation and apoptosis was determined using a primary malignant meningioma cell culture. Results: Atypical and malignant meningiomas showed higher levels of phospho-Akt compared with benign tumors, and their proliferation could be inhibited by PI3K blocking using wortmannin. PI3K inhibition did not induce apoptosis in malignant meningioma cells. In contrast, expression of phospho-Raf and phospho-MAPK was decreased in aggressive meningiomas compared with benign tumors, but MAPK inhibition by PD98059 resulted in tumor cell apoptosis and decreased proliferation. Reduced MAPK activation was associated with meningioma recurrence, and PI3K activation was associated with poor preclinical condition and brain invasion of malignant meningiomas. Conclusions: Both MAPK and PI3K/Akt pathways are activated at different levels in benign and malignant meningiomas. Activation of PI3K/Akt signaling contributes to the aggressive behavior of malignant meningiomas, whereas MAPK activation is involved in both proliferation and apoptosis of malignant meningiomas.
The effect of resveratrol on the inflammatory response and delayed onset muscle soreness after a marathon in male athletes: a randomised, double-blind, placebo-controlled pilot study
Authors: Markus W Laupheimer
Journal: British Journal of Sports Medicine (2011)

Objectives Resveratrol, a natural polyphenolic flavonoid antioxidant is known to have numerous health benefits and to act as a potent anti-inflammatory substance. This study was undertaken to investigate the inflammatory responses and delayed onset of muscle soreness after the London Marathon, and whether it is altered by Resveratrol. Design and setting Double placebo-controlled randomised trial conducted at the London Marathon, 2010. Methods Seven healthy male athletes were recruited for the study. Participants were randomised to either Resveratrol or placebo. The Resveratrol group was treated with 600 mg Resveratrol daily for 7 days immediately before the marathon. Blood was taken 48 h before the marathon and 18–32 h after the marathon. Samples were analysed for white blood cell count (WBC) and C reactive protein (CRP). To assess delayed onset muscle soreness a visual analogue scale (VAS) score was taken at the same times as the blood samples. The prepost changes were compared between the groups using the Mann–Whitney U test. Results There was no significant difference between the two groups in terms of changes occurring between pre and post-tests for WBC, CRP or VAS (p=0.857, 0.629 and 0.70 respectively). Conclusion This pilot study could not find a difference in immune response or delayed onset of muscle soreness between Resveratrol and placebo after the London Marathon 2010. Further investigations are needed with longer treatment time and higher doses, analysing additional parameters like interleukins for a possible effect of Resveratrol on the inflammatory response due to extensive exercise.
A STRIKING CASE OF CHICKEN-POX SIMULATING SMALL-POX: CHARACTERISTICS WHICH DISTINGUISHED IT
Authors: W. M. Wanklyn
Journal: BMJ (1924)

CHICKENjL-POX S11ULTN SMALL-POX.IMEDICAL JOcNaIAS -blood pressure is tlhe important factor.This is what oone would expect.In cases of tuberculosis, in which the blood pressure is low, inidicating poor power of resistanice, we may presumie that sufficient antibodies are not beinig formed, and tlhe patient demands and responids to the stimiiulating action of the tuberculin.Wheni the blood pressure is higher probably sufficient antibodies are beinig formed, and therefore there is less need for, and conise-
Molecular analysis of the induction of immunoglobulin E synthesis in human B cells by interleukin 4 and engagement of CD40 antigen.
Authors: S K Shapira, D Vercelli, H H Jabara, S M Fu, R S Geha
Journal: The Journal of Experimental Medicine (1992)

The molecular events leading to immunoglobulin E (IgE) synthesis in human sIgE- B cells stimulated with interleukin 4 (IL-4) and anti-CD40 monoclonal antibody (mAb) 626.1 were analyzed. Anti-CD40 mAb increased the levels of IL-4-induced germline C epsilon transcripts and induced the production of mature C epsilon mRNA. These effects were dependent on the presence of IL-4. Nested primer PCR revealed deletional switch recombination occurring only in B cell stimulated with both IL-4 and anti-CD40 mAb. DNA sequence analysis of switch fragments showed direct S mu/S epsilon joining, without the deletions or duplications within S mu often found in B cells stimulated with IL-4 and Epstein-Barr virus. Analysis of the switch junction map sites showed "hot spots" for recombination within S mu, but not within S epsilon. These findings indicate that IL-4 provides a signal to B cells to induce germline C epsilon transcription and concurrent CD40 engagement induces S mu/S epsilon deletional switch recombination, production of mature C epsilon mRNA, and IgE synthesis.
Randomized trial of high-dose chemotherapy and hematopoietic progenitor-cell support in operable breast cancer with extensive lymph node involvement: final analysis with 7 years of follow-up
Authors: J.G. Schrama, I.F. Faneyte, J.H. Schornagel, J.W. Baars, J.L. Peterse, M.J. van de Vijver, O. Dalesio, H. van Tinteren, E.J.T. Rutgers, D.J. Richel, S. Rodenhuis
Journal: Annals of Oncology (2002)

BackgroundThe aim of this study was to present an update of overall (OS) and disease-free survival (DFS) and to evaluate the correlation between outcome and pathological findings at surgery in a randomized trial of high-dose chemotherapy following neoadjuvant chemotherapy and surgery in high-risk breast cancer patients.Patients and methodsNinety-seven women <60 years of age with breast cancer and extensive axillary lymph node involvement received three courses of FE120C (5-fluorouracil 500 mg/m2, epirubicin 120 mg/m2, cyclophosphamide 500 mg/m2) followed by surgery. Eighty-one patients were randomized to receive either a fourth FE120C course alone or a fourth FE120C course followed by high-dose chemotherapy (cyclophosphamide 6 g/m2, thiotepa 480 mg/m2, carboplatin 1600 mg/m2). We performed a univariate analysis on possible prognostic factors and analyzed the sites of relapse.ResultsAfter a median follow-up of 6.9 years, 47 (48%) patients were alive, of whom 36 (38%) were without disease. Sixty patients relapsed after treatment. One patient died of myelodysplastic syndrome, without a relapse. In intention-to-treat analysis, the 5-year DFS rates were 47.5% in the conventional treatment arm and 49% in the high-dose arm, and the 5-year OS rates were 62.5% and 61%, respectively. In the univariate analysis, the clinical T-stage before chemotherapy and the number of tumor-positive axillary lymph nodes after induction chemotherapy (P = 0.027) were significant prognostic factors for OS. The same factors (both P = 0.06) plus the estrogen receptor (P = 0.08) were borderline significant factors for DFS.ConclusionsAfter a median follow-up of 6.9 years there was no difference in OS or DFS rates between the two treatment groups. The number of tumor-positive axillary lymph nodes after induction chemotherapy and the clinical T-stage before chemotherapy were significant factors for OS.
Cystic fibrosis: current survival and population estimates to the year 2000.
Authors: J S Elborn, D J Shale, J R Britton
Journal: Thorax (1991)

BACKGROUND: Survival from cystic fibrosis is increasing rapidly. Estimates of the extent of this improvement should allow health care facilities to be planned to deal with the expanding population of patients with cystic fibrosis. Estimates of life expectancy are also essential if accurate information on current prognosis is to be given to parents of an affected child, or to prospective parents deciding whether to proceed with a pregnancy where the fetus may be affected. METHODS: Survival trends in the national data on cystic fibrosis have been analysed to produce estimates of the likely size of the cystic fibrosis population over the next decade and to predict the life expectancy of children born with cystic fibrosis in the years up to 1990. RESULTS: In England and Wales the estimated number of patients with cystic fibrosis is at present about 5200, of whom 3300 (63%) are aged under 16 years. By the year 2000 the total population will increase to 6000, with 3400 (57%) aged under 16. Thus the number of children with cystic fibrosis will remain fairly constant over the next 10 years, whereas adult numbers will increase by about 36% (from 1901 to 2577). The median life expectancy of children with cystic fibrosis born in 1990 is estimated to be 40 years, double that of 20 years ago. CONCLUSION: This study suggests that health service provision for children will not need to change substantially over the next 10 years whereas services for adults will need to increase by about a third. Parents can be counselled that the median life expectancy of a newborn child with cystic fibrosis is currently likely to be of the order of 40 years.
STUDIES ON THE CELLULAR IMMUNOLOGY OF ACUTE BACTERIEMIA
Authors: W. Barry Wood, Mary Ruth Smith, William D. Perry, John W. Berry
Journal: The Journal of Experimental Medicine (1951)

Evidence has been presented that the introduction of large numbers of bacteria into the blood stream causes a widespread intravascular reaction, characterized by the sticking of leucocytes to the endothelium of capillaries, arterioles, and venules. The adherent granulocytes promptly become motile and thus potentially phagocytic. This intravascular leucocytic response affords a rapid and efficient mobilization of a vast number of active phagocytes within the blood stream. In some of the smaller vessels of both the systemic and pulmonary circulation the reaction is accompanied by the deposition of what appears to be intravascular fibrin. Direct observation by the rabbit ear chamber technique has revealed that leucocytes thus mobilized in small peripheral vessels are capable of phagocyting fully encapsulated Friedländer’s bacilli in the absence of antibody. Ingestion of the encapsulated blood-borne bacteria results from surface phagocytosis and occurs primarily in those vessels in which the flow of blood is either slowed or has temporarily stopped altogether. Leucocytes can be seen to phagocyte the organisms by first trapping them against the walls of the vessels or against adjacent leucocytes. Bacteria caught in the interstices of the intravascular "fibrin" may likewise be immobilized and readily phagocyted. Thus granulocytes, without the aid of opsonins, are able to ingest and destroy encapsulated blood-borne bacteria by the same mechanisms that operate in extravascular tissues. It is concluded from these studies that intravascular surface phagocytosis by polymorphonuclear leucocytes supplements the well known phagocytic activities of the reticulo-endothelial cells and therefore serves as an important defense of the host in acute infections caused by encapsulated bacteria and complicated by bacteriemia.
Lactose digestion by human jejunal biopsies: the relationship between hydrolysis and absorption.
Authors: D J Dawson, R W Lobley, P C Burrows, V Miller, R Holmes
Journal: Gut (1986)

The relationship between lactose hydrolysis and absorption of released glucose was investigated by determining the kinetics of lactose digestion by jejunal biopsies incubated in vitro. Lactase activity in intact biopsies correlated with conventional assay of tissue homogenates (r = 0.85, p less than 0.001), and glucose uptake from 28 mM lactose was directly proportional to lactase activity (r = 0.95, p less than 0.001) in 21 subjects with normal lactase levels, six with hypolactasia (primary or secondary to coeliac disease) and two with lactose intolerance but normal lactase activity. Kinetic analysis at 0.56-56 mM lactose in five normal subjects showed saturable kinetics for hydrolysis (app Km = 33.9 +/- 2.2 mM; app Vmax = 26.5 +/- 1.1 nmol/min/mg dry weight) but glucose uptake could be fitted to a model either of saturable uptake (app Kt = 47.2 +/- 0.3 mM; app Jmax = 14.1 +/- 0.2 nmol/min/mg) or saturable uptake plus a linear component (app Kt = 21.3 +/- 1.15; app Jmax = 4.59 +/- 0.12; app Kd = 0.093 +/- 0.010 nmol/min/mg/mM). The proportion of glucose taken into the tissue did not significantly exceed 50% of the total released at any lactose concentration suggesting the lack of an efficient capture mechanism for the released glucose. The results suggest that lactose hydrolysis is the rate limiting step in the overall absorption of glucose from lactose in vitro, and that the relationship between hydrolysis and absorption is the same in normal subjects and in hypolactasic subjects.
Clonidine, Depression, and Smoking Cessation
Authors: J R Hughes
Journal: JAMA (1988)

Pharmacologic treatment of smoking is not a new idea.<sup>1</sup>However, the search for effective pharmacologic treatments for smoking has increased dramatically in the last ten years due to the realization that smoking is a dependence disorder<sup>2</sup>; that behavioral strategies are not having a large effect on the prevalence of smoking<sup>3</sup>; and that nicotine dependence is becoming more prevalent in smokers due to a selection process.<sup>4</sup>This latter process is occurring because smokers who are quitting appear to be smokers who are less dependent on nicotine. Thus, if this trend continues, in ten to 20 years the population of smokers will be almost exclusively smokers who are highly dependent on nicotine. See also page 2863. Nicotine gum was introduced in 1984 as the first proven pharmacologic aid for smoking cessation.<sup>5</sup>Encouraged by this success, other nicotine replacement therapies, eg, nicotine patch<sup>6</sup>and nicotine nasal spray,
ON THE MODE OF PRESENTATION OF DEAD CHILDREN IN LABOUR
Authors: J. M. Duncan
Journal: BMJ (1855)

on Midwifery, etc. IT is wel known that death of the fetus in utero is a frequent cause of malpresentation.In other words, dead fcstuses much more fequently present the breech or shoulder than the living.This is eaily proved by statis- tics.For instance, "during the seven years that Dr.Collins had charge of the Dublin Lyig-in-Hospital, 16,654 children were born within the house.Of these 16,654 children, 15,533 were born alive, and 1,121 dead.Of the 1,121 dead children, many no doubt died during labour; but 527 of them were in a putrid state, and, consequently, may be correctly regarded as having perished in utero, and before labour commenced.Among the 15,533 children bo alive, 278 presented preternaturally, or 1 in 67; 250 presented by the pelvic extremity, or 1 in 62; 28 presented by the upper extremity, or 1 in 555; 15,255 presented by the head, or 98 in 100.On the other hand, among the 527 children born putrid, as many as 94 presented preterna- turally, or 1 in 5; 88 presented by the pelvic extremity, or 1 in 6; 6 presented by the upper extremity, or I in 88; 433 presented by the head, or 83 in 100."*Presentations of Liring and of Dead Children.Presentations.Living.
Circumventing genetic restriction of protection against malaria with multigene DNA immunization: CD8+ cell-, interferon gamma-, and nitric oxide-dependent immunity.
Authors: D L Doolan, M Sedegah, R C Hedstrom, P Hobart, Y Charoenvit, S L Hoffman
Journal: The Journal of Experimental Medicine (1996)

Despite efforts to develop vaccines that protect against malaria by inducing CD8+ T cells that kill infected hepatocytes, no subunit vaccine has been shown to circumvent the genetic restriction inherent in this approach, and little is known about the interaction of subunit vaccine-induced immune effectors and infected hepatocytes. We now report that immunization with plasmid DNA encoding the plasmodium yoelii circumsporozoite protein protected one of five strains of mice against malaria (H-2d, 75%); a PyHEP17 DNA vaccine protected three of the five strains (H-2a, 71%; H-2k, 54%; H-2d, 26%); and the combination protected 82% of H-2a, 90% of H-2k, and 88% of H-2d mice. Protection was absolutely dependent on CD8+ T cells, INF-gamma, or nitric oxide. These data introduce a new target of protective preerythrocytic immune responses, PyHEP 17 and its P. falciparum homologue, and provide a realistic perspective on the opportunities and challenges inherent in developing malaria vaccines that target the infected hepatocyte.
Exhale airway bypass stents for emphysema
Authors: Zaid Zoumot
Journal: Thorax (2011)

Existing treatment options for severe homogenous emphysema are limited, with dynamic airways collapse and gas trapping minimising the benefits of drug therapy. There has been interest in therapies that address these features more directly. The bronchoscopic lung volume reduction with Exhale airway stents for emphysema trial study group recently reported their findings in The Lancet . The group undertook a multicentre, double-blind, randomised, sham-controlled trial at 38 specialist respiratory centres worldwide. Three hundred and fifteen …