tbuckley/cabot-search huggingface dataset:
Polymorphisms A1026G and G369C of CDKN1A/p21 and p53 genes in lung cancer
Authors: Alla I. Dmitrieva, Irina A. Kuznetsova, Sergei S. Rakitin, Vjacheslav V. Novitskiy
Journal: European Respiratory Journal (2011)

In this study, we analyzed the polymorphisms of genes regulating the cell cycle and p53 CDKN1A/p21 as factors of genetic predisposition to lung cancer in patients with lung cancer. We examined 65 patients with lung cancer (average age 54±8 years) and 100 healthy blood donors (average age 52±6 years). Diagnosis of lung cancer was confirmed morphologically, endoscopically and radiologically. The study of these genes was performed by PCR/RFLP analysis.

72-G/C- polymorphism analysis of p53 gene has revealed a slight increase in the frequency of the variant G72C-genotype of the p53 gene in lung cancer patients compared with those in healthy (38 and 32% respectively, P = 0,695).

We have analyzed two polymorphisms CDKN1A/p21: 1026 A/G and 369 G/C-polymorphism in the 5$'$-gene promoter. In analyzing the 1026-AG-p21 gene polymorphism was found halving the frequency of AG-genotype in lung cancer patients compared with those in healthy individuals (38 and 77%, respectively; OR = 0,72, CI95%0,081–3,95). The frequency of AA-genotype of p21 gene in patients and healthy was respectively 50 and 19% for the GG-genotype of p21 gene was respectively 10 and 4% (OR=5,39, CI95%1,27–24,29). This enabled us to assume that the AG-genotype performs protective and AA-genotype - the role of predisposing to cancer of the lung. The frequency of A-allele in lung cancer patients was higher than in healthy individuals (70 and 57,5%, respectively). OR of lung cancer for carriers of the A-allele was 1,72 (CI95%1,05-2,83).

In the analysis of G369C-gene polymorphism in p21 is shown, the frequency of C-allele in lung cancer patients significantly exceeded that in healthy individuals (20,77 and 11%, respectively; OR=2,12 CI95%1,10-4,09).
Ventricular Dynamics in Atrial Fibrillation
Authors: HAROLD T. DODGE, FREDERIC T. KIRKHAM, CLARA V. KING
Journal: Circulation (1957)

During atrial fibrillation there are beat-to-beat changes of ventricular rate, end-diastolic volume, end-diastolic pressure, and arterial pressure or resistance to ventricular ejection. The effect of these variables on left ventricular dynamics in man has been approached by studying single sequences of beats in patients with atrial fibrillation. An index of changes of left ventricular volume has been determined from the electrokymogram of left cardiac border. Left ventricular pressures have been measured at surgery or by the transbronchial technic. These studies provide a better understanding of the hemodynamics of the left ventricle during atrial fibrillation and demonstrate another approach to the study of left ventricular function in man.
The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3-L1 cells and human mesenchymal stem cells
Authors: Tsai-Hua Chung, Si-Han Wu, Ming Yao, Chen-Wen Lu, Yu-Shen Lin, Yann Hung, Chung-Yuan Mou, Yao-Chang Chen, Dong-Ming Huang
Journal: Biomaterials (2007)
The Role of the Liver in Glucagon Metabolism
Authors: Jonathan B. Jaspan, Alice H-J. Huen, Colin G. Morley, A. Rahim Moossa, Arthur H. Rubenstein
Journal: Journal of Clinical Investigation (1977)

Total plasma immunoreactive pancreatic glucagon (IRG) was measured in samples taken simultaneously from the proximal portal vein and superior vena cava of 26 healthy rats. The portal-peripheral ratio of IRG was 2.80±0.25, the portal-peripheral difference (Δ) 124±15 pg/ml, and percentage extraction 58±3. Gel filtration of paired portal and peripheral vein samples showed that reduction in the 3,500-dalton IRG component (glucagon) in peripheral samples accounted for almost all the differences, there being minimal and inconsistent changes in the high molecular weight (>40,000) fraction. The portal-peripheral ratio of the 3,500-dalton glucagon was 5.24±1.10, the portal-peripheral difference 130±33 pg/ml, and the percentage extraction 81±5.
Cancer of the ampulla of Vater: chromosome 17p allelic loss is associated with poor prognosis
Authors: A Scarpa
Journal: Gut (2000)

<h3>BACKGROUND</h3> Cancer of the ampulla of Vater kills 60% of affected patients. Local spread of the tumour (T stage) is the only reliable prognostic factor. Nevertheless, any cancer stage includes long term survivors and patients dying from the disease. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. <h3>AIM</h3> To evaluate if allelic losses (LOH) of chromosomes 17p and 18q may be of prognostic value in multivariate survival analysis. <h3>METHODS</h3> We examined 53 ampullary cancers for chromosome 17p and 18q LOH using microsatellite markers and DNA from paraffin embedded tumours. All patients were treated by surgery alone (pancreaticoduodenectomy). Multivariate survival analysis included age, sex, tumour size, macroscopic appearance, grade of differentiation, T stage, lymph node metastasis, and chromosome 17p and 18q status. <h3>RESULTS</h3> Chromosome 17p and 18q LOH were detected in 28 (53%) and 18 (34%) cancers, respectively. Multivariate survival analysis indicated chromosome 17p status as an independent prognostic factor together with T stage. The five year survival for chromosome 17p retention and 17p loss was 80% and 7%, respectively. The risk of death from cancer within the five year follow up period for patients with cancers harbouring chromosome 17p LOH was 11 times higher than that of patients with cancers retaining chromosome 17p (p&lt;0.0001), regardless of the tumour stage at diagnosis. <h3>CONCLUSIONS</h3> Chromosome 17p status is an independent prognostic factor among ampullary cancers at the same stage. The combined use of T stage and chromosome 17p status may help in deciding whether ampullary cancer patients require additional therapy other than surgery alone.
Prognostic Relevance of Treatment Response Measured by Flow Cytometric Residual Disease Detection in Older Patients With Acute Myeloid Leukemia
Authors: Sylvie D. Freeman, Paul Virgo, Steve Couzens, David Grimwade, Nigel Russell, Robert K. Hills, Alan K. Burnett
Journal: Journal of Clinical Oncology (2013)

Older patients with acute myeloid leukemia (AML) have a high relapse rate after standard chemotherapy. We investigated whether measuring chemotherapy sensitivity by multiparameter flow cytometric minimal residual disease (MFC-MRD) detection has prognostic value in patients older than age 60 years or is simply a surrogate for known age-related risk factors.Eight hundred ninety-two unselected patients treated intensively in the United Kingdom National Cancer Research Institute AML16 Trial were assessed prospectively for MFC-MRD during treatment. Eight hundred thirty-three patients had leukemia-associated immunophenotypes (LAIPs) identified by pretreatment screening. Four hundred twenty-seven patients entered complete remission (CR) after one or two courses (designated C1 and C2, respectively) and were MFC-MRD assessable by LAIP detection in CR bone marrow for at least one of these time points. MRD positivity was defined as residual disease detectable by LAIP.MFC-MRD negativity, which was achieved in 51% of patients after C1 (n = 286) and 64% of patients after C2 (n = 279), conferred significantly better 3-year survival from CR (C1: 42% v 26% in MRD-positive patients, P < .001; C2: 38% v 18%, respectively; P < .001) and reduced relapse (C1: 71% v 83% in MRD-positive patients, P < .001; C2: 79% v 91%, respectively; P < .001), with higher risk of early relapse in MRD-positive patients (median time to relapse, 8.5 v 17.1 months, respectively). In multivariable analysis, MRD status at the post-C1 time point independently predicted survival, identifying a subgroup of intermediate-risk patients with particularly poor outcome. However, survival benefit from gemtuzumab ozogamicin was not associated with MFC-MRD chemotherapy sensitivity.Early assessment of treatment response using flow cytometry provides powerful independent prognostic information in older adults with AML, lending support to the incorporation of MRD detection to refine risk stratification and inform clinical trial design in this challenging group of patients.
The minimally important difference and patient acceptable symptom state for the Raynaud's condition score in patients with Raynaud's phenomenon in a large randomised controlled clinical trial
Authors: Puja P Khanna, Paul Maranian, Jeff Gregory, Dinesh Khanna
Journal: Annals of the Rheumatic Diseases (2009)

Background The Raynaud's condition score (RCS) is a validated outcome measure for Raynaud's phenomenon (RP). Objective To assess the minimally important difference (MID) and patient acceptable symptom state (PASS) for RCS in patients with RP. Subjects and methods Patients with active RP (n=162) (mean RCS &gt;25 (0–100 visual analogue scale) participated in a placebo-controlled, crossover randomised clinical trial (RCT). Data from the two treatment groups were combined for this analysis. Retrospective and prospective anchors were administered during the RCT. MID groups were defined as the group who reported being somewhat better (anchor #1) and a one-step change from “unbearable” to “very severe”, etc (anchor #2). Patients were considered to have achieved PASS if they rated their Raynaud's condition as “ very mild ” or “ mild ” at the last study visit. Results The mean age of participants was 48.9 years and the mean baseline RCS was 46.4 points. The RCS change score for the MID improvement group ranged from −13.9 to −14.3 points and PASS estimate was 34.0 points. Conclusion The MID and PASS estimates for RCS are 14–15 points for improvement and 34 points, respectively, on a 0–100 scale in a large RCT of patients with active RP. This information can aid in interpreting RCS in future RP trials.
Intracoronary Doppler– and Quantitative Coronary Angiography–Derived Predictors of Major Adverse Cardiac Events After Stent Implantation
Authors: Michael Haude, Dietrich Baumgart, Edoardo Verna, Jan J. Piek, Chris Vrints, Peter Probst, Raimund Erbel
Journal: Circulation (2001)

Background —Distal coronary flow velocity reserve (CVR) is significantly improved after a successful balloon angioplasty (PTCA). Furthermore, a postinterventional CVR &gt;2.5 and a percent diameter stenosis (%DS) ≤35% are predictive for a low incidence of major adverse cardiac events (MACE) at 6 months of 16%. Similar results are lacking for coronary stenting. Methods and Results —In 150 patients, baseline and hyperemic coronary flow velocities were recorded with a Doppler guidewire distal to the target lesion and in an unobstructed reference artery before and after PTCA, after stenting, and at 6 months. Distal CVR and relative CVR (CVR rel ) were calculated. Logistic regression and receiver operating characteristic analyses were applied to determine prognostic cutoff values of CVR, CVR rel , %DS, and minimal lumen diameter separately and in combination to predict MACE at 6 months. After stenting, CVR (2.96±0.87 versus 2.40±0.7; P =0.001), CVR rel (1.02±0.24 versus 0.81±0.24; P =0.001), and minimal lumen diameter (2.98±0.56 versus 2.11±0.74 mm; P =0.001) were significantly higher than after PTCA. Thirty-three patients developed MACE. A postinterventional CVR rel &gt;0.88 was the best single predictor of MACE, with an incidence of 6.8%, whereas the combination of a CVR rel &gt;0.88 and a %DS ≤11.2% predicted an incidence of MACE of 1.5%. Conclusions —Measurement of CVR rel and %DS after stent implantation are best suitable to predict MACE at 6 months.
Emergency Department Recognition of Mental Disorders and Short-Term Outcome of Deliberate Self-Harm
Authors: Mark Olfson, Steven C. Marcus, Jeffrey A. Bridge
Journal: American Journal of Psychiatry (2013)

Objective The authors sought to characterize the short-term risks of repeat self-harm and psychiatric hospital admission for deliberate self-harm patients discharged from emergency departments to the community, focusing on recognition of mental disorders in the emergency department. Method A retrospective longitudinal cohort analysis of national Medicaid claims data was conducted of adults 21–64 years of age with deliberate self-harm who were discharged from emergency departments (N=5,567). Rates and adjusted risk ratios are presented of repeat self-harm visits and inpatient psychiatric admission during the 30 days following the initial emergency visit. Results Approximately 9.7% of self-harm visits were followed by repeat self-harm visits and 13.6% by inpatient psychiatric admissions within 30 days after the initial emergency visit. The rate of repeat self-harm visits was inversely related to recognition of a mental disorder in the emergency department (adjusted risk ratio [ARR]=0.66, 95% CI=0.55–0.79) and directly related to recent diagnosis of anxiety disorders (ARR=1.56, 95% CI=1.30–1.86) or personality disorders (ARR=1.67, 95% CI=1.19–2.34). Recognition of a mental disorder in the emergency department was inversely related to repeat self-harm among patients with no recent mental disorder diagnosis (ARR=0.57, 95% CI=0.41–0.79); any recent mental disorder diagnosis (ARR=0.70, 95%=0.57–0.87); and depressive (ARR=0.71, 95% CI=0.54–0.94), bipolar (ARR=0.70, 95% CI=0.51–0.94), and substance use (ARR=0.71, 95% CI=0.53–0.96) disorder diagnoses. Recognition of a mental disorder was also inversely related to subsequent inpatient psychiatric admission (ARR=0.81, 95% CI=0.71–0.93). Conclusions Adults who are discharged to the community after emergency visits for deliberate self-harm are at high short-term risk of repeat deliberate self-harm and hospital admission, although these risks may be attenuated by clinical recognition of a mental disorder in the emergency department.
Pharmacokinetics and Tissue Distribution of a Ribozyme Directed Against Hepatitis C Virus RNA Following Subcutaneous or Intravenous Administration in Mice
Authors: Patrice A. Lee, Lawrence M. Blatt, Karin S. Blanchard, Karyn S. Bouhana, Pamela A. Pavco, Laurent Bellon, Jennifer A. Sandberg
Journal: Hepatology (2000)

A nuclease resistant ribozyme targeting the 5′ untranslated region (5′ UTR) of hepatitis C virus (HCV) at site 195 has been identified. To investigate the therapeutic utility of this ribozyme, we evaluated the pharmacokinetics and tissue distribution with two labeled forms of this ribozyme. [ 32 P]-labeled ribozyme was administered as a single subcutaneous (SC) or intravenous (IV) bolus at a dose of 10 mg/kg or 30 mg/kg in C57Bl/6 mice. Regardless of route of administration, peak liver concentrations achieved were greater than the concentration necessary to inhibit HCV-IRES-luciferase expression in cell culture. The ribozyme was well absorbed after SC administration (89%) and had an elimination half-life of 23 minutes. To show intracellular localization of the ribozyme in target tissue, a tetramethyl rhodamine (TMR)-labeled ribozyme was administered as a single SC or IV bolus at a dose of 30 mg/kg in C57Bl/6 mice. Mice treated SC or IV with TMR-labeled ribozyme had positive fluorescence in the liver from 15 minutes to 48 hours after dosing. Definite positive fluorescence was still present at 72 hours in the mice dosed via the IV route. At early time points (15 and 30 minutes postinjection), nuclear and possibly cytoplasmic fluorescence was present in the hepatocytes, and sinusoidal fluorescence was intense. At the later time points, fluorescence became more punctate. Abundant staining was often present in Kupffer cells. This study confirms the retention of ribozyme in liver cells and supports the potential of an anti-HCV ribozyme as a therapeutic agent for treatment of chronic hepatitis C. (Hepatology 2000;32:640-646.)
Bevacizumab, Capecitabine, and Oxaliplatin As Neoadjuvant Therapy for Patients With Potentially Curable Metastatic Colorectal Cancer
Authors: Brigit Gruenberger, Dietmar Tamandl, Johannes Schueller, Werner Scheithauer, Christoph Zielinski, Friedrich Herbst, Thomas Gruenberger
Journal: Journal of Clinical Oncology (2008)

Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis, but can benefit from perioperative chemotherapy and disease resection. Bevacizumab improves outcomes in patients with metastatic CRC; however, its impact on surgical complications and hepatic regeneration after liver resection remains to be determined.Fifty-six patients with metastatic CRC with liver metastases potentially curable by resection were eligible for this single-center, nonrandomized phase II trial. Eligibility criteria defined patients at high risk of early recurrence. Patients received biweekly bevacizumab plus capecitabine and oxaliplatin for six cycles. The sixth cycle of therapy did not include bevacizumab, resulting in 5 weeks between the last administration of bevacizumab and surgery.Objective response to neoadjuvant chemotherapy was achieved in 41 patients (73%). Fifty-two patients underwent liver resection including 11 with synchronous primary tumor resection. No increased intraoperative bleeding events or wound-healing complications were observed and only three patients (6%) required perioperative blood transfusions. Further surgery was necessary in a single patient. Postoperative liver function and regeneration were normal in all but one patient. No postoperative mortality occurred and morbidity was encountered in 11 patients (20%). The mean length of postoperative hospitalization was 9 days (+/- 4.0).These data suggest that bevacizumab can be safely administered until 5 weeks before liver resection in patients with metastatic CRC without increasing the rate of surgical or wound healing complications or severity of bleeding. To our knowledge, they are also the first to show that neoadjuvant bevacizumab does not affect liver regeneration after resection.
Extroversion of Bladder
Authors: A. W. M. Robson
Journal: BMJ (1885)

98:8°, and the pulse was seldom as high as 100, and never above it.The child is now a sturdy little boy over twelve months old.'I fear Dr. Godson must add this case as an unsuccessful one to his list.Yet I think the death would be more fairly credited to the disease that remained than to the operation, though at the time it was ascribed, in part -at least, to carbolic acid poisoning.It was, of coumre, unsatisfactory to be obliged to leave the epitheliomatous cervix, but the patient was in such an exhausted condition, that to have removed it would have been immediately fatal.Even Porro's operation had to be performed with a rapidity which, without effi- cient assistance, would have been impossible.
Early T Cell Activation Correlates with Expression of Apoptosis Markers in Patients with End-Stage Renal Disease
Authors: Pascal Meier, Eric Dayer, Edouard Blanc, Jean-Pierre Wauters
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. End-stage renal failure (ESRF) and chronic hemodialysis (HD) induce a state of immunodeficiency that involves T cell-mediated responses. A decreased T cell number combined with a reduced T cell lifespan and an increased T cell activation might play a role in the immune impairment associated with ESRF and chronic HD. Increased T cell activation associated with immunodeficiency suggests that activated T cells may be driven to apoptosis. To test this hypothesis, CD3+ T cell activation (CD69) and apoptosis (annexin V, CD95 (Fas), and DNA fragmentation) were analyzed in a case control study after blood draw sampling (ex vivo), in culture conditions, and after phytohemagglutinin or anti-CD3 stimulation. Ex vivo evaluation of T cells showed an increased number of activated CD69+ T cells in chronic HD patients (142 +/- 5 cells/mm3) compared with patients with ESRF (115 +/- 2 cells/mm3, P = 0.04) and controls (74 +/- 2 cells/mm3, P = 0.0006). These data were confirmed in culture conditions and after stimulation. Similarly, annexin V and CD95 (Fas)-positive T cells were more numerous in both patient groups than in controls, irrespective of the experimental conditions (P < or = 0.005 for both markers), and their percentage was always significantly higher in chronic HD patients than in patients with ESRF. The amount of DNA fragmentation was also significantly higher in the cultured resting T cells of chronic HD patients (37 +/- 3%) than in those of patients with ESRF (25 +/- 3%) and controls (20 +/- 2%) (P = 0.01). Percentage of cultured resting T cells expressing both CD69 and annexin V markers was higher in chronic HD patients (17 +/- 4%) than in patients with ESRF (10 +/- 4%) and controls (6 +/- 2%), (P = 0.005). After stimulation (phytohemagglutinin or anti-CD3), CD69+ T cell apoptosis increased by 2.4-fold in chronic HD patients compared with 1.8-fold in patients with ESRF and only 1.2-fold in controls (P = 0.001). T cells from chronic HD patients and patients with ESRF thus showed an aberrant state of early activation that contrasted with an increased proportion of annexin V and CD95 (Fas)-positive T cells engaged in apoptosis, as confirmed by DNA fragmentation. Increased susceptibility to early activated T cell apoptosis is not only associated with uremia, but is also enhanced by HD procedure. This may account for the T lymphopenia, progressive immunodeficiency, and increased infection risk seen in these patients.
A polyarticular onset predicts erosive and deforming disease in psoriatic arthritis
Authors: R Queiro-Silva
Journal: Annals of the Rheumatic Diseases (2002)

To analyse the factors predicting erosive-deforming arthropathy in patients with psoriatic arthritis (PsA).A prospective cohort study was undertaken with 71 patients diagnosed as having PsA (44 men and 27 women, mean age 47 (SD 12) years). At the recruitment period patients had disease without evidence of radiological damage. Patients were studied and followed up according to a standard protocol from January 1991 to June 2001. Erosive and deforming disease was defined by the presence of erosions, joint space narrowing, subluxation, and/or ankylosis of peripheral joints. Univariate and multivariate analyses were performed to evaluate factors predicting erosive and deforming disease.At the end of the study 32 of 71 (45%) patients had developed erosive and deforming disease. Among them, 18 of 32 (56%) had a polyarticular onset, two of 32 (6%) showed a distal interphalangeal joint disease onset, six of 32 (19%) presented with oligoarthritis, and six of 32 (19%) presented with axial disease as the form of disease onset (p=0.001). Mean time to detect erosions or joint space narrowing was 20 (SD 4) months. Men showed fewer erosions than women (p=0.05). Patients who carried the HLA-B27 antigen showed less erosive disease than patients who lacked it (p=0.05). Patients with erosive and deforming disease had poorer functional performance than those without it as measured with the Health Assessment Questionnaire (HAQ) and the American College of Rheumatology (ACR) criteria (p<0.05 with both measurements). In multivariate analysis, only a polyarticular onset remained as an indicator of erosive and deforming disease (odds ratio (OR) 37, 95% confidence interval (95% CI) 3.6 to 88, p=0.025).A polyarticular onset (five or more swollen joints) of PsA was the unique independent risk factor which predicted the appearance of erosive and deforming disease over time. These data may be useful for clinicians treating patients with PsA, as it may guide treatment towards a more aggressive and earlier intervention.
FULL-TERM EXTRAUTERINE PREGNANCY WITH LIVING CHILD
Authors: W. A. Steel
Journal: BMJ (1934)

ConclusionThere was no apparent cause, and this case must be considered as primary or idiopathic agranulocytic angina.It would appear that in any case of ulceration of the mouth, tongue, fauces, or -any other mucous membrane without definite cause, yet with severe constitutional disturbance, an examination of the blood should be carried out to exclude the possibility of agranulocytic angina.My thanks are due to Dr. \VT.F.