tbuckley/cabot-search huggingface dataset:
GELATIN AS A PLASMA SUBSTITUTE: THE EFFECTS OF INTRAVENOUS INFUSION OF GELATIN ON CARDIAC OUTPUT AND OTHER ASPECTS OF THE CIRCULATION OF NORMAL PERSONS, OF CHRONICALLY ILL PATIENTS, AND OF NORMAL VOLUNTEERS SUBJECTED TO LARGE HEMORRHAGE
Authors: A. G. Fletcher, James D. Hardy, C. Riegel, C. E. Koop
Journal: Journal of Clinical Investigation (1945)

Recent experimental and clinical studies have demonstrated that especially prepared ossein gelatin, administered intravenously, is a safe and effective plasma substitute for use in the treatment of shock and is useful in certain hypoproteinemic states in man (I to 3).Other investigators have suggested that gelatin shows some promise as a source of nutritional protein for intravenous administration (4, 5).It has seemed important to us that these studies should be extended to in- clude observations on the dynamics of the circu- lation as affected by the intravenous infusion of the gelatin colloid in man.There are available a number of reports on the circulatory effects of the intravenous infusion of saline or glucose solutions (6 to 11) and of colloidal solutions such as whole blood, plasma, or acacia (12 to 15).We have observed the changes in pulse rate, blood pressure, blood volume, venous pressure, cardiac output, hematocrit, and plasma protein produced by the intravenous infusion of gelatin in normal subjects, chronically ill patients, and volunteers subjected to experimental hemor- rhage.The effect of hemorrhage per se proved to be of particular interest and has been the subject of a separate paper prepared in collaboration with others who were concurrently engaged in the study of this problem (16,17).Of the work reported here, the clinical studies carried out on normal persons, on patients, and on the volunteers after hemorrhage, recorded in Tables II, III, and IV, were made by Doctors Fletcher and Hardy.Unfortunately, these au- thors were inducted into the armed forces before the study was quite completed.The chemical analyses were all performed by Dr. Riegel.The estimations of blood volume were all made by Dr.Koop.The special study on venous pressure after gelatin infusion was carried out by Dr. Koop with the kind assistance of Dr. R. L. Mayock.
REJECTION OF ASCITES TUMOR ALLOGRAFTS
Authors: Gideon Berke, Karen A. Sullivan, Bernard Amos
Journal: The Journal of Experimental Medicine (1972)

Peritoneal exudate cells (PEC), obtained after the rejection of EL4 leukemia by BALB/c mice, are much more effective in the specific in vitro destruction of 51Cr-labeled EL4 cells than are spleen, thymus, lymph node, or peripheral blood lymphocytes. The presence of a large number of effector cells at the site of graft rejection is reflected in the potent cytolytic activity seen in vitro. Effector cells temporarily lose cytolytic reactivity when treated with trypsin but regain reactivity with time. This recovery occurs in normal as well as in immune serum. The destructive reactivity of PEC is increased when macrophages are removed. The remaining population of nonadherent PEC is composed primarily of small- to medium-sized lymphocytes. Complex tissue culture media are not needed, but there is a definite requirement for serum. The required serum component is heat stable, nondialyzable, and is not consumed during the reaction. The use of an ascites allograft system made these observations possible and permitted the isolation of those host cells intimately associated with rejection.
Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis
Authors: L. H. D. van Tuyl, M. Boers, W. F. Lems, R. B. Landewe, H. Han, S. van der Linden, M. van de Laar, R. Westhovens, J. C. van Denderen, M.-L. Westedt, A. J. Peeters, P. Jacobs, T. W. J. Huizinga, H. van de Brink, B. A. C. Dijkmans, A. E. Voskuyl
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Background</h3> COBRA (for 'COmbinatie therapie Bij Rheumatoide Artritis') combination therapy is effective for the treatment of rheumatoid arthritis (RA), but long-term safety is unknown. This study evaluates survival, comorbidities and joint damage in the original COBRA trial cohort. <h3>Methods</h3> In the COBRA trial, 155 patients with early RA were treated with sulfasalazine (SSZ) monotherapy (SSZ group) or a combination of step-down prednisolone, methotrexate (MTX) and SSZ (COBRA group). The current 11-year follow-up study of the COBRA trial invited all original patients and performed protocollised scrutiny of clinical records, questionnaires, physical examination, laboratory and imaging tests. <h3>Results</h3> In all, 152 out of 155 patients yielded at least partial data. After a mean of 11 years follow-up, 18 (12%) patients had died, 6 COBRA patients and 12 SSZ patients, HR 0.57 (95% CI 0.21 to 1.52). Treatment for hypertension was significantly more prevalent in the COBRA group (p=0.02) with similar trends for diabetes and cataract. Conversely, hypercholesterolaemia, cancer and infection showed a trend in favour of COBRA. Other comorbidities such as cardiovascular disease and fractures appeared in similar frequency. Radiographic findings suggest as a minimum sustained benefit for COBRA therapy, that is, difference in joint damage but similar subsequent progression rates after 5 years. Imputation to compensate for selective dropout suggests increasing benefit for COBRA, that is, difference in yearly progression rates similar to that seen in the first 5 years of follow-up. <h3>Conclusions</h3> After 11 years, initial COBRA combination therapy resulted in numerically lower mortality and similar prevalence of comorbidity compared with initial SSZ monotherapy. In addition, lower progression of joint damage suggests long-term disease modification.
Membranoproliferative Glomerulonephritis Type II (Dense Deposit Disease)
Authors: Gerald B. Appel, H. Terence Cook, Gregory Hageman, J. Charles Jennette, Michael Kashgarian, Michael Kirschfink, John D. Lambris, Lynne Lanning, Hans U. Lutz, Seppo Meri, Noel R. Rose, David J. Salant, Sanjeev Sethi, Richard J.H. Smith, William Smoyer, Hope F. Tully, Sean P. Tully, Patrick Walker, Michael Welsh, Reinhard Wu[Combining Diaeresis]rzner, Peter F. Zipfel
Journal: Journal of the American Society of Nephrology (2005)

Membranoproliferative glomerulonephritis type II (MPGN II) is a rare disease characterized by the deposition of abnormal electron-dense material within the glomerular basement membrane of the kidney and often within Bruch's membrane in the eye. The diagnosis is made in most patients between the ages of 5 and 15 yr, and within 10 yr, approximately half progress to end-stage renal disease, occasionally with the late comorbidity of visual impairment. The pathophysiologic basis of MPGN II is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade. In most patients, loss of complement regulation is caused by C3 nephritic factor, an autoantibody directed against the C3 convertase of the AP, but in some patients, mutations in the factor H gene have been identified. For the latter patients, plasma replacement therapy prevents renal failure, but for the majority of patients, there is no proven effective treatment. The disease recurs in virtually all renal allografts, and a high percentage of these ultimately fail. The development of molecular diagnostic tools and new therapies directed at controlling the AP of the complement cascade either locally in the kidney or at the systemic level may lead to effective treatments for MPGN II.
A Trial of Intraoperative Low-Tidal-Volume Ventilation in Abdominal Surgery
Authors: Emmanuel Futier, Jean-Michel Constantin, Catherine Paugam-Burtz, Julien Pascal, Mathilde Eurin, Arthur Neuschwander, Emmanuel Marret, Marc Beaussier, Christophe Gutton, Jean-Yves Lefrant, Bernard Allaouchiche, Daniel Verzilli, Marc Leone, Audrey De Jong, Jean-Etienne Bazin, Bruno Pereira, Samir Jaber
Journal: New England Journal of Medicine (2013)

Lung-protective ventilation with the use of low tidal volumes and positive end-expiratory pressure is considered best practice in the care of many critically ill patients. However, its role in anesthetized patients undergoing major surgery is not known.In this multicenter, double-blind, parallel-group trial, we randomly assigned 400 adults at intermediate to high risk of pulmonary complications after major abdominal surgery to either nonprotective mechanical ventilation or a strategy of lung-protective ventilation. The primary outcome was a composite of major pulmonary and extrapulmonary complications occurring within the first 7 days after surgery.The two intervention groups had similar characteristics at baseline. In the intention-to-treat analysis, the primary outcome occurred in 21 of 200 patients (10.5%) assigned to lung-protective ventilation, as compared with 55 of 200 (27.5%) assigned to nonprotective ventilation (relative risk, 0.40; 95% confidence interval [CI], 0.24 to 0.68; P=0.001). Over the 7-day postoperative period, 10 patients (5.0%) assigned to lung-protective ventilation required noninvasive ventilation or intubation for acute respiratory failure, as compared with 34 (17.0%) assigned to nonprotective ventilation (relative risk, 0.29; 95% CI, 0.14 to 0.61; P=0.001). The length of the hospital stay was shorter among patients receiving lung-protective ventilation than among those receiving nonprotective ventilation (mean difference, -2.45 days; 95% CI, -4.17 to -0.72; P=0.006).As compared with a practice of nonprotective mechanical ventilation, the use of a lung-protective ventilation strategy in intermediate-risk and high-risk patients undergoing major abdominal surgery was associated with improved clinical outcomes and reduced health care utilization. (IMPROVE ClinicalTrials.gov number, NCT01282996.).
Allergy to bumblebee venom I. Occupational anaphylaxis to bumblebee venom: diagnosis and treatment
Authors: H. de Groot, C. de Graaf‐in‘t Veld, R. Gerth van Wijk
Journal: Allergy (1995)

We describe six patients with severe occasional anaphylaxis, caused by stings of bumblebees. Sensitization to bumblebee venom was confirmed by intracutaneous tests and RAST with purified bumblebee venom. Three patients changed their occupation and will probably not be stung by bumblebees in the future. The other patients started immunotherapy with newly purified bumblebee venom extract. After 1 year of treatment, no severe side‐effects had occurred and clinical benefit in two patients could be demonstrated, as both skin sensitivity or serum IgE to bumblebee venom had decreased. Moreover, both patients were unresponsive to in‐hospital sting challenge.
Optimal Windows of Statin Use for Immediate Infarct Limitation
Authors: Shoji Sanada, Hiroshi Asanuma, Tetsuo Minamino, Koichi Node, Seiji Takashima, Hiroko Okuda, Yoshiro Shinozaki, Akiko Ogai, Masashi Fujita, Akio Hirata, Jiyoong Kim, Yoshihiro Asano, Hidezo Mori, Hitonobu Tomoike, Soichiro Kitamura, Masatsugu Hori, Masafumi Kitakaze
Journal: Circulation (2004)

Background— Although statins are reported to have a cardioprotective effect, their immediate direct influence on ischemia-reperfusion injury and the underlying mechanisms remain obscure. We investigated these issues an in vivo canine model. Methods and Results— Dogs were subjected to coronary occlusion (90 minutes) and reperfusion (6 hours) immediately after injection of pravastatin (0.2, 2, or 10 mg/kg), pitavastatin (0.01, 0.1, or 0.5 mg/kg), or cerivastatin (0.5, 5, or 50 μg/kg). Then myocardial phosphatidylinositol 3-kinase (PI3-K) and 5′-nucleotidase activities were measured, as well as infarct size. After 15 minutes of reperfusion, pravastatin caused dose-dependent activation of Akt and ecto-5′-nucleotidase in the ischemic zone, and the effect was significant at higher doses. Pitavastatin also significantly increased these activities, and its optimal dose was within the clinical range, whereas cerivastatin caused activation at the lowest dose tested. In all cases, both Akt and ecto-5′-nucleotidase showed activation in parallel, and this activation was completely abolished by wortmannin, a PI3-K inhibitor. The magnitude of the infarct-limiting effect paralleled the increase in Akt and ecto-5′-nucleotidase activity and was blunted by administration of wortmannin, α,β-methyleneadenosine-5′-diphosphate, or 8-sulfophenyltheophylline during reperfusion. Both collateral flow and the area at risk were comparable for all groups. Conclusions— Activation of ecto-5′-nucleotidase after ischemia by PI3-K activation may be crucial for immediate infarct-size limitation by statins. There seems to be an optimal dose for each statin that is independent of its clinical cholesterol-lowering effect.
<i>PIK3CA</i>and<i>PIK3CB</i>Inhibition Produce Synthetic Lethality when Combined with Estrogen Deprivation in Estrogen Receptor–Positive Breast Cancer
Authors: Robert J. Crowder, Chanpheng Phommaly, Yu Tao, Jeremy Hoog, Jingqin Luo, Charles M. Perou, Joel S. Parker, Melinda A. Miller, David G. Huntsman, Li Lin, Jacqueline Snider, Sherri R. Davies, John A. Olson, Mark A. Watson, Anthony Saporita, Jason D. Weber, Matthew J. Ellis
Journal: Cancer Research (2009)

Several phosphoinositide 3-kinase (PI3K) catalytic subunit inhibitors are currently in clinical trial. We therefore sought to examine relationships between pharmacologic inhibition and somatic mutations in PI3K catalytic subunits in estrogen receptor (ER)-positive breast cancer, in which these mutations are particularly common. RNA interference (RNAi) was used to determine the effect of selective inhibition of PI3K catalytic subunits, p110alpha and p110beta, in ER(+) breast cancer cells harboring either mutation (PIK3CA) or gene amplification (PIK3CB). p110alpha RNAi inhibited growth and promoted apoptosis in all tested ER(+) breast cancer cells under estrogen deprived-conditions, whereas p110beta RNAi only affected cells harboring PIK3CB amplification. Moreover, dual p110alpha/p110beta inhibition potentiated these effects. In addition, treatment with the clinical-grade PI3K catalytic subunit inhibitor BEZ235 also promoted apoptosis in ER(+) breast cancer cells. Importantly, estradiol suppressed apoptosis induced by both gene knockdowns and BEZ235 treatment. Our results suggest that PI3K inhibitors should target both p110alpha and p110beta catalytic subunits, whether wild-type or mutant, and be combined with endocrine therapy for maximal efficacy when treating ER(+) breast cancer.
The frequency and significance of thiopurine <i>S</i> -methyltransferase gene polymorphisms in azathioprine-treated renal transplant recipients
Authors: F.J. Moloney, P. Dicker, P.J. Conlon, D.C Shields, G.M. Murphy
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Sir, Interindividual variation in the metabolism of azathioprine, commonly used post‐transplant, can be due to the presence of genetic polymorphisms affecting the thiopurine S‐methyltransferase gene (TPMT).1 Standard dosing of azathioprine can expose patients with TPMT variants to a larger burden of immunosuppression over the duration of transplant.2 The aim of this retrospective study was to define the frequency and significance of TPMT nonfunctional mutations in a renal transplant population. This study was primarily carried out in Beaumont Hospital, the national renal transplant centre in Ireland. Additional patients were recruited from the Adelaide and Meath Hospital, Tallaght, Dublin. Ethical approval for this study was received. Patients older than 16 years of age were interviewed and examined by one observer (F.J.M.). Data were collected using a standardized questionnaire as previously described.3 Renal transplant recipients (RTR) with and without skin cancer were genotyped for TPMT*2 (G238C), TPMT*3A (G460A, A719G), TPMT*3B (G460A) and TPMT*3C (A719G). Genomic DNA was isolated from a peripheral venous blood sample and genotyping was performed using the AmplifluorTM method by K Biosciences (http://www.kbioscience.co.uk). Categorical variables were tested using χ2 and Mantel–Haenszel statistics while continuous variables were tested using Student's t‐test and Wilcoxon two‐sample test. In the analyses, older age, longer duration since transplantation, fairer skin type and higher total sun exposure score (P < 0·0001) were shown to be predictors of increased skin cancer risk. The association of TPMT variants with skin cancer risk was therefore initially tested using a Cochrane–Armitage trend test and adjusted odds ratios (ORs) were then calculated based on a logistic regression, factoring in the above covariates.
Local Excision Alone Without Irradiation for Ductal Carcinoma In Situ of the Breast: A Trial of the Eastern Cooperative Oncology Group
Authors: Lorie L. Hughes, Molin Wang, David L. Page, Robert Gray, Lawrence J. Solin, Nancy E. Davidson, Mary Ann Lowen, James N. Ingle, Abram Recht, William C. Wood
Journal: Journal of Clinical Oncology (2009)

To determine the risk of ipsilateral breast events in patients with ductal carcinoma in situ (DCIS) treated with local excision without irradiation.Patients with either low- or intermediate-grade DCIS measuring 2.5 cm or smaller, or high-grade DCIS measuring 1 cm or smaller who had microscopic margin widths of 3 mm or wider and no residual calcifications on postoperative mammograms were eligible for a prospective trial conducted from 1997 to 2002 by the Eastern Cooperative Oncology Group and North Central Cancer Treatment Group. Patients entered in 2000 and later could take tamoxifen if they wished. Median age at last surgery for the entire population was 60 years (range, 28 to 88 years), and median tumor sizes in the two strata were 6 mm and 5 mm, respectively.With a median follow-up of 6.2 years, the 5-year rate of ipsilateral breast events in the 565 eligible patients in the low/intermediate grade stratum was 6.1% (95% CI, 4.1% to 8.2%). With a median follow-up of 6.7 years, this incidence for the 105 eligible patients in the high-grade stratum was 15.3% (95% CI, 8.2% to 22.5%).Rigorously evaluated and selected patients with low- to intermediate-grade DCIS with margins 3 mm or wider had an acceptably low rate of ipsilateral breast events at 5 years after excision without irradiation. Patients with high-grade lesions had a much higher rate, suggesting that excision alone is inadequate treatment. Further follow-up is necessary to document long-term results.
Oesophageal pH monitoring in Barrett's oesophagus
Authors: C S Neumann
Journal: Gut (2002)

We wish to comment on an interesting paper published previously in Gut which we inadvertently overlooked at the time. Fass et al ( Gut 2001; 48 :310–13) reported that there was a positive correlation between percentage time that oesophageal pH was less than 4 in 24 hours and the length of the columnar lined segment in 15 patients with long segment Barrett's oesophagus. Some years ago, we published data concerning 24 hour ambulatory oesophageal pH monitoring in untreated patients with Barrett's oesophagus and compared the results with those obtained in patients with reflux oesophagitis but no Barrett's oesophagus.1 pH monitoring was performed within one week of endoscopy. We found overlap in the 24 hour pH results between Barrett's patients and patients with reflux oesophagitis. However, among Barrett's patients, those with moderate to severe reflux oesophagitis above Barrett's segment had more acid reflux than those with mild reflux oesophagitis or none. At the time we did not correlate pH monitoring results with the length of the Barrett's segment but have now reviewed our pH data and have been able to correlate these results with the length of the columnar lined …
Ankylosing spondylitis is associated with the anthrax toxin receptor 2 gene (<i>ANTXR2</i>)
Authors: T Karaderi, S M Keidel, J J Pointon, L H Appleton, M A Brown, D M Evans, B P Wordsworth
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> <i>ANTXR2</i> variants have been associated with ankylosing spondylitis (AS) in two previous genome-wide association studies (GWAS) (p∼9×10<sup>−8</sup>). However, a genome-wide significant association (p&lt;5×10<sup>−8</sup>) was not observed. We conducted a more comprehensive analysis of <i>ANTXR2</i> in an independent UK sample to confirm and refine this association. <h3>Methods</h3> A replication study was carried out with 2978 cases and 8365 controls. Then, these were combined with non-overlapping samples from the two previous GWAS in a meta-analysis. Human leukocyte antigen (HLA)-B27 stratification was also performed to test for <i>ANTXR2</i>-HLA-B27 interaction. <h3>Results</h3> Out of nine single nucleotide polymorphisms (SNP) in the study, five SNPs were nominally associated (p&lt;0.05) with AS in the replication dataset. In the meta-analysis, eight SNPs showed evidence of association, the strongest being with rs12504282 (OR=0.88, p=6.7×10<sup>−9</sup>). Seven of these SNPs showed evidence for association in the HLA-B27-positive subgroup, but none was associated with HLA-B27-negative AS. However, no statistically significant interaction was detected between HLA-B27 and <i>ANTXR2</i> variants. <h3>Conclusions</h3> <i>ANTXR2</i> variants are clearly associated with AS. The top SNPs from two previous GWAS (rs4333130 and rs4389526) and this study (rs12504282) are in strong linkage disequilibrium (r<sup>2</sup>≥0.76). All are located near a putative regulatory region. Further studies are required to clarify the role played by these <i>ANTXR2</i> variants in AS.
Perceived Risks of Heart Disease and Cancer Among Cigarette Smokers
Authors: J Z Ayanian, P D Cleary
Journal: JAMA (1999)

ContextCigarette smoking causes more preventable deaths from cardiovascular disease and cancer than any other modifiable risk factor, but smokers may discount the increased personal risk they face from continued smoking.ObjectiveTo assess smokers' perceptions of their risks of heart disease and cancer.Design and SettingTelephone and self-administered survey in 1995 of a probability sample of US households with telephones.ParticipantsA total of 3031 adults aged 25 to 74 years, including 737 current smokers (24.3%).Main Outcome MeasuresRespondents with no history of myocardial infarction (MI) (96.2%) or cancer (92.9%) assessed their risk of these conditions relative to other people of the same age and sex. Among current smokers, perceived risks were analyzed by demographic and clinical factors using logistic regression.ResultsOnly 29% and 40% of current smokers believed they have a higher-than-average risk of MI or cancer, respectively, and only 39% and 49% of heavy smokers (≥40 cigarettes per day) acknowledged these risks. Even among smokers with hypertension, angina, or a family history of MI, 48%, 49%, and 39%, respectively, perceived their risk of MI as higher than average. In multivariate analyses, older (≥65 years), less educated (< high school graduate), and light smokers (1-19 cigarettes per day) were less likely than younger, more educated, and heavy smokers to perceive an increased personal risk of MI or cancer.ConclusionsMost smokers do not view themselves at increased risk of heart disease or cancer. As part of multifaceted approaches to smoking cessation, physicians and public health professionals should identify and educate smokers who are not aware of smoking-related health risks.