tbuckley/cabot-search huggingface dataset:
Endoscopic screening of relatives of patients with colorectal cancer
Authors: L M Hunt, P S Rooney, J D Hardcastle, N C Armitage
Journal: Gut (1998)

The risk of colorectal cancer is higher among relatives of those affected. The neoplastic yield reported from screening such individuals varies enormously between studies and depends on the age and strength of the family history of those screened.To ascertain the neoplastic yield of endoscopic screening of first degree relatives of patients with colorectal cancer by age and familial risk.A total of 330 individuals with a family history of colorectal cancer.Endoscopic screening conducted according to a protocol.Adenomas were found in 12%, and adenomas larger than 1 cm in 8%, of "high risk" individuals screened primarily by colonoscopy. Of those with neoplasia, 26% had lesions at or proximal to the splenic flexure. Neoplasia was found in 9.5% of individuals at lower familial risk, screened primarily by 60 cm flexible sigmoidoscopy, 4% of whom had neoplasia larger than 1 cm in size or cancer. Neoplastic yield was greatest in the fourth and fifth decades in those at highest risk, but increased with age in those at lower risk.For individuals with two or more first degree relatives, or relatives who have developed colorectal cancer at a young age, colonoscopy appears to be the only satisfactory method of screening, but 60 cm flexible sigmoidoscopy may be useful in those at lower levels of risk.
MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases
Authors: Minjia Yu, Hao Zhou, Junjie Zhao, Nengming Xiao, Sanjoy Roychowdhury, David Schmitt, Bingqing Hu, Richard M. Ransohoff, Clifford V. Harding, Amy G. Hise, Stanley L. Hazen, Anthony L. DeFranco, Paul L. Fox, Richard E. Morton, Paul E. Dicorleto, Maria Febbraio, Laura E. Nagy, Jonathan D. Smith, Jian-an Wang, Xiaoxia Li
Journal: The Journal of Experimental Medicine (2014)

Low-grade systemic inflammation is often associated with metabolic syndrome, which plays a critical role in the development of the obesity-associated inflammatory diseases, including insulin resistance and atherosclerosis. Here, we investigate how Toll-like receptor–MyD88 signaling in myeloid and endothelial cells coordinately participates in the initiation and progression of high fat diet–induced systemic inflammation and metabolic inflammatory diseases. MyD88 deficiency in myeloid cells inhibits macrophage recruitment to adipose tissue and their switch to an M1-like phenotype. This is accompanied by substantially reduced diet-induced systemic inflammation, insulin resistance, and atherosclerosis. MyD88 deficiency in endothelial cells results in a moderate reduction in diet-induced adipose macrophage infiltration and M1 polarization, selective insulin sensitivity in adipose tissue, and amelioration of spontaneous atherosclerosis. Both in vivo and ex vivo studies suggest that MyD88-dependent GM-CSF production from the endothelial cells might play a critical role in the initiation of obesity-associated inflammation and development of atherosclerosis by priming the monocytes in the adipose and arterial tissues to differentiate into M1-like inflammatory macrophages. Collectively, these results implicate a critical MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.
HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies
Authors: Michael B. Maris, Dietger Niederwieser, Brenda M. Sandmaier, Barry Storer, Monic Stuart, David Maloney, Effie Petersdorf, Peter McSweeney, Michael Pulsipher, Ann Woolfrey, Thomas Chauncey, Ed Agura, Shelly Heimfeld, John Slattery, Ute Hegenbart, Claudio Anasetti, Karl Blume, Rainer Storb
Journal: Blood (2003)
Factor-Xa-induced mitogenesis and migration require sphingosine kinase activity and S1P formation in human vascular smooth muscle cells
Authors: Andreas Böhm, Anja Flößer, Swen Ermler, Anke C Fender, Anja Lüth, Burkhard Kleuser, Karsten Schrör, Bernhard H Rauch
Journal: Cardiovascular Research (2013)

Sphingosine-1-phosphate (S1P) is a cellular signalling lipid generated by sphingosine kinase-1 (SPHK1). The aim of the study was to investigate whether the activated coagulation factor-X (FXa) regulates SPHK1 transcription and the formation of S1P and subsequent mitogenesis and migration of human vascular smooth muscle cells (SMC).FXa induced a time- (3-6 h) and concentration-dependent (3-30 nmol/L) increase of SPHK1 mRNA and protein expression in human aortic SMC, resulting in an increased synthesis of S1P. FXa-stimulated transcription of SPHK1 was mediated by the protease-activated receptor-1 (PAR-1) and PAR-2. In human carotid artery plaques, expression of SPHK1 was observed at SMC-rich sites and was co-localized with intraplaque FX/FXa content. FXa-induced SPHK1 transcription was attenuated by inhibitors of Rho kinase (Y27632) and by protein kinase C (PKC) isoforms (GF109203X). In addition, FXa rapidly induced the activation of the small GTPase Rho A. Inhibition of signalling pathways which regulate SPHK1 expression, inhibition of its activity or siRNA-mediated SPHK1 knockdown attenuated the mitogenic and chemotactic response of human SMC to FXa.These data suggest that FXa induces SPHK1 expression and increases S1P formation independent of thrombin and that this involves the activation of Rho A and PKC signalling. In addition to its key function in coagulation, this direct effect of FXa on human SMC may increase cell proliferation and migration at sites of vessel injury and thereby contribute to the progression of vascular lesions.
Possible interaction between ionizing radiation, smoking, and gender in the causation of meningioma
Authors: P. Flint-Richter, L. Mandelzweig, B. Oberman, S. Sadetzki
Journal: Neuro-Oncology (2011)

Data on the association between smoking and meningioma are inconsistent. The aim of this study was to assess the role of smoking in radiation- and non-radiation-related meningiomas. The study was designed as a 4-group case-control study, balanced for irradiation, including 160 irradiated meningioma case patients, 145 irradiated control subjects, 82 nonirradiated case patients, and 135 nonirradiated control subjects. The sources of these groups included a cohort of individuals who underwent radiotherapy (mean dose, 1.5 Gy to the brain) during childhood for treatment of tinea capitis, claims filed for radiation damage in the framework of a compensation law, and the Israel Cancer Registry. All tests of statistical significance were 2-sided. A statistically significantly elevated risk of meningioma was found among men who had ever smoked, compared with those who were never smokers (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.09-4.15), increasing with smoking pack-years from 1.67 to 2.69 for <10 to >20 pack-years, respectively. Among women, an interaction between radiation and smoking was observed, expressed by a significant protective effect for meningioma (OR, 0.32; 95% CI, 0.14-0.77), with a strong dose-response association (P < .01) in non-irradiated women and a nonsignificant increased risk of meningioma among those who were irradiated (OR, 1.23; 95% CI, 0.68-2.23). Variation in the association between smoking and meningioma may be explained by effects of distinct host factors, such as past exposure to ionizing radiation and/or hormonal factors.
The interaction of human plasma glycosaminoglycans with plasma lipoproteins. II. Hemagglutination studies.
Authors: P V Donnelly, N Di Ferrante, R L Jackson
Journal: Circulation Research (1978)

Formalinized, tannic acid-treated sheep erythrocytes coated with low density lipoproteins (LSL) or apoprotein B (apo-B) are are agglutinated by anti-apo-B immunserum. Those coated with high density lipoproteins (HDL) or apoprotein A-I(apo-A-I) are agglutinated by anti-apo-A-I immunserum. These coated formocells have been used to study the interactions of lipoproteins and apoproteins with plasma glycosaminoglycans (GAG). The sulfate-rich species of plasma GAG agglutinates cells coated with LDL, HDL, apo-B, and apo-A-I at ionic concentrations above 0.15 M. The less-sulfated species of plasma GAG does not agglutinate the coated cells but inhibits the agglutination caused by the sulfate-rich species. Treatment of the sulfate-rich GAG with papain causes a reduction in molecular weight by one-half and also causes a loss of its agglutinating activity. These results suggest that the sulfate-rich plasma GAG, consisting of two glycan chains linked to a peptide backbone, cause agglutination by binding to two or more formocells. In contrast, the less-sulfated plasma GAG, consisting of single, short glycan chains, are incapable of causing agglutination but may prevent it by covering specific binding sites present on the coated cells.
Contribution of lymphatic absorption to loss of ultrafiltration and solute clearances in continuous ambulatory peritoneal dialysis.
Authors: R A Mactier, R Khanna, Z Twardowski, H Moore, K D Nolph
Journal: Journal of Clinical Investigation (1987)

The contribution of peritoneal cavity lymphatic absorption to ultrafiltration kinetics and solute clearances in continuous ambulatory peritoneal dialysis was evaluated in patients with normal (group 1) and high (group 2) peritoneal permeability X area during 4-h exchanges using 2 liters 2.5% dextrose dialysis solution with 30 g added albumin. Cumulative lymphatic drainage in all continuous ambulatory peritoneal dialysis (CAPD) patients averaged 358 +/- 47 ml per 4-h exchange and reduced cumulative net transcapillary ultrafiltration at the end of the exchange by 58 +/- 7.2%. The peak ultrafiltration volume was observed before osmotic equilibrium between serum and dialysate was reached and occurred when the net transcapillary ultrafiltration rate had decreased to equal the lymphatic absorption rate. Thereafter the lymphatic absorption rate exceeded the net transcapillary ultrafiltration rate, and intraperitoneal volume decreased. Extrapolated to 4 X 2 liters, 2.5% dextrose, 6-h exchanges per d, lymphatic drainage reduced potential daily net ultrafiltration by 83.2 +/- 10.2%, daily urea clearance by 16.9 +/- 1.9%, and daily creatinine clearance by 16.5 +/- 1.9%. Although lymphatic absorption did not differ between the two groups, lymphatic drainage caused a proportionately greater reduction in net ultrafiltration in group 2 (P less than 0.025), because these patients had more rapid dialysate glucose absorption (P less than 0.05) and less cumulative transcapillary ultrafiltration (P less than 0.01). These findings indicate that cumulative lymphatic drainage significantly reduces net ultrafiltration and solute clearances in CAPD and that ultrafiltration failure in CAPD occurs when daily lymphatic absorption equals or exceeds daily transcapillary ultrafiltration. Reduction of lymphatic absorption may provide a means for future improvement in the efficiency of CAPD.
Hip Osteoarthritis and the Risk of All‐Cause and Disease‐Specific Mortality in Older Women: A Population‐Based Cohort Study
Authors: Kamil E. Barbour, Li‐Yung Lui, Michael C. Nevitt, Louise B. Murphy, Charles G. Helmick, Kristina A. Theis, Marc C. Hochberg, Nancy E. Lane, Jennifer M. Hootman, Jane A. Cauley
Journal: Arthritis & Rheumatology (2015)

Objective To determine the risk of all‐cause and disease‐specific mortality among older women with hip osteoarthritis (OA) and to identify mediators in the causal pathway. Methods Data were from the Study of Osteoporotic Fractures, a US population‐based cohort study of 9,704 white women age ≥65 years. The analytic sample included women with hip radiographs at baseline (n = 7,889) and year 8 (n = 5,749). Mortality was confirmed through October 2013 by death certificates and hospital discharge summaries. Radiographic hip OA (RHOA) was defined as a Croft grade of ≥2 in at least 1 hip (definite joint space narrowing or osteophytes plus 1 other radiographic feature). Results The mean ± SD followup time was 16.1 ± 6.2 years. The baseline and year 8 prevalence of RHOA were 8.0% and 11.0%, respectively. The cumulative incidence (proportion of deaths during the study period) was 67.7% for all‐cause mortality, 26.3% for cardiovascular disease (CVD) mortality, 11.7% for cancer mortality, 1.9% for gastrointestinal disease mortality, and 27.8% for all other mortality causes. RHOA was associated with an increased risk of all‐cause mortality (hazard ratio 1.14 [95% confidence interval 1.05–1.24]) and CVD mortality (hazard ratio 1.24 [95% confidence interval 1.09–1.41]) adjusted for age, body mass index, education, smoking, health status, diabetes, and stroke. These associations were partially explained by the mediating variable of physical function. Conclusion RHOA was associated with an increased risk of all‐cause and CVD mortality among older white women followed up for 16 years. Dissemination of evidence‐based physical activity and self‐management interventions for hip OA in community and clinical settings can improve physical function and might also contribute to lower mortality.
The effect of the pattern of cardiac sympathetic activity on myocardial contractile force and norepinephrine overflow in the dog heart.
Authors: M N Levy, B Blattberg
Journal: Circulation Research (1976)

The left of right cardiac sympathetic nerves in open-chest, anesthetized dogs were stimulated at mean frequencies of 2 or 4 Hz. The stimuli were applied intermittently, in patterns with repetition rates or either 60/min or 15/min, to simulate the spontaneous patterns of sympathetic neural activity that occur synchronously with the cardiac or respiratory cycles, respectively. With either repetition rate, intermittent stimulation of the left sympathetic nerves was about 10-20% less effective in enhancing myocardial contractile force (CF) and about 10% less effective in increasing coronary sinus blood flow than was steady stimulation at the same mean frequency. With right-sided stimulation, there was no appreciable difference between steady and intermettent stimulation patterns with respect to the effect on heart rate. With either left-or right-sided stimulation, the rate of norepinephrine (NE) overflow into the coronary sinus blood was 20-40% less with intermittent than with steady stimulation. Cocaine administration did not materially affect this difference in NE overflow. It was concluded that the higher instantaneous frequencies that prevail during intermittent stimulation result in a reduction in the rate of NE release at the sympathetic postganglionic nerve endings in the heart.
Further evidence for an association between LCI and FEV<sub>1</sub>in patients with PCD: Figure 1
Authors: Sylvia Nyilas, Anne Schlegtendal, Sophie Yammine, Carmen Casaulta, Philipp Latzin, Cordula Koerner-Rettberg
Journal: Thorax (2015)

Further evidence for an association between LCI and FEV 1 in patients with PCDWe have taken keen interest in the current discussion on the meaning of the lung clearance index (LCI) in patients with primary ciliary dyskinesia (PCD).In patients with cystic fibrosis (CF), LCI from the nitrogen multiple-breath gas washout (N 2 -MBW) test has become a sensitive marker for detection of ventilation inhomogeneity with a good correlation between LCI and FEV 1 . 1 However, in patients with PCD, two studies failed to find a correlation for the FEV 1 and LCI. 1 2 This difference in functional measures between CF and PCD was recently challenged by Boon et al, 3 showing a robust correlation between LCI and FEV 1 in patients with PCD.In the carefully written accompanying editorial, several factors were given to explain, among others these, differences between studies. 4 Our aim is now to add further data to this discussion.We performed N 2 -MBW measurements and spirometry in 47 patients with PCD at a mean (SD; range) age of 14.7 (6.9; 4.0-42.3)years, using an Exhalyzer D (EcoMedics, Duernten, Switzerland) and Jaeger MasterScreen body plethysmograph (CareFusion, Höchberg, Germany) on the same day.z-Scores were defined of a healthy reference population for FEV 1 5 and from an in-house healthy population (n=46) measured with the same equipment for LCI.We found a good correlation between LCI and FEV 1 z-scores (coefficient: -2.95, 95% CI -3.92 to -1.97, p<0.001,R 2 0.45, r -0.67, see figure 1).Using absolute values adjusted for age, gender and height, the correlation between LCI and FEV 1 remained significant in a robust way (coefficient: -3.24, 95% CI -4.51 to -1.97, p<0.001,R 2 0.49, r-0.70).In our cohort, the association was independent of age (coefficient: -2.88 for <14 years and -2.70 for >14 years) and disease severity (coefficient: -3.36 for those with FEV 1 <-1 z-score and -3.42 for those with FEV 1 >-1 z-score).This suggests that it is neither the use of z-scores nor the different age or disease severity that leads to the discrepant findings of previous studies.Taken together, we confirm results from Boon et al of a good correlation between LCI and FEV 1 in patients with PCD.This association was independent of age or disease severity.Besides different pieces of equipment and tracer gases used, 4 another reason for discrepancies between studies 1 3 might still be the different genetic background leading to distinct PCD phenotypes between regions and centres.
Brief adrenomedullin inhalation leads to sustained reduction of pulmonary artery pressure
Authors: K. von der Hardt, M.A. Kandler, M. Chada, A. Cubra, E. Schoof, K. Amann, W. Rascher, J. Dötsch
Journal: European Respiratory Journal (2004)

The effect of aerosolised adrenomedullin (ADM), a potent vasodilator peptide, on pulmonary artery pressure was studied for 24 h in a surfactant-depleted piglet model. Animals received either aerosolised ADM (50 ng·kg −1 ·min −1 , ADM, n=6), or aerosolised normal saline solution (control, n=6). Aerosol therapy was performed for a 2 h treatment period followed by a 22 h observation period. Ventilator settings were adapted to keep arterial oxygen tension and carbon dioxide arterial tension between 13.3–14.6 kPa and 4.9–5.7 kPa, respectively. Aerosolised ADM reduced mean pulmonary artery pressure (MPAP) compared with the control group (end-point median 24 h after therapy start: ΔMPAP −14.0 versus −8.0 mmHg; 23.5 h after therapy start). After therapy start, mean systemic arterial pressure (MAP) was not significantly different between the groups (end-point median: MAP ADM 70 (61/74) versus control 72 (54/81) mmHg). Endothelin-1, a potent pulmonary vasoconstrictor, is regulated by ADM via cAMP. Twenty two hours after inhalation of aerosolised ADM, endothelin-1 mRNA in lung tissue and endothelin-1 protein expression in pulmonary arteries was reduced compared with controls (median semi-quantitative immunhistochemical score: ADM 0.21, control 0.76). Aerosolised adrenomedullin significantly reduced mean pulmonary artery pressure independently of arterial oxygen tension.
Prolonged vasoconstriction of resistance arteries involves vascular smooth muscle actin polymerization leading to inward remodelling
Authors: Marius C. Staiculescu, Edgar L. Galiñanes, Guiling Zhao, Uri Ulloa, Minshan Jin, Mirza I. Beig, Gerald A. Meininger, Luis A. Martinez-Lemus
Journal: Cardiovascular Research (2013)

Inward remodelling of the resistance vasculature is predictive of hypertension and life-threatening cardiovascular events. We hypothesize that the contractile mechanisms responsible for maintaining a reduced diameter over time in response to prolonged stimulation with vasoconstrictor agonists are in part responsible for the initial stages of the remodelling process. Here we investigated the role of vascular smooth muscle (VSM) actin polymerization on agonist-induced vasoconstriction and development of inward remodelling.Experiments were conducted in Sprague-Dawley rat resistance vessels isolated from the cremaster and mesentery. Within blood vessels, actin dynamics of VSM were monitored by confocal microscopy after introduction of fluorescent actin monomers through electroporation and by differential centrifugation to probe globular (G) and filamentous (F) actin content. Results indicated that 4 h of agonist-dependent vasoconstriction induced inward remodelling and caused significant actin polymerization, elevating the F-/total-actin ratio. Inhibition of actin polymerization prevented vessels from maintaining prolonged vasoconstriction and developing inward remodelling. Activation of the small GTPases Rho/Rac/Cdc42 also increased the F-/total-actin ratio and induced inward remodelling, while inhibition of Rho kinase or Rac-1 prevented inward remodelling. Disruption of the actin cytoskeleton reversed the inward remodelling caused by prolonged vasoconstriction, but did not affect the passive diameter of freshly isolated vessels.These results indicate that vasoconstriction-induced inward remodelling is in part caused by the polymerization of actin within VSM cells through activation of small GTPases.
Flutamide withdrawal syndrome: its impact on clinical trials in hormone-refractory prostate cancer.
Authors: H I Scher, W K Kelly
Journal: Journal of Clinical Oncology (1993)

PURPOSE To evaluate the effect of discontinuation of the antiandrogen, flutamide, in patients with metastatic prostate cancer who are progressing on hormonal therapy. PATIENTS AND METHODS Thirty-six patients with progressive disease on hormonal treatment that included flutamide had discontinuation of the antiandrogen. Thirty-five (95%) had progressive increases in prostate-specific antigen (PSA) levels, despite castrate levels of testosterone. Twenty-five patients (69%) were treated with combined androgen blockade (orchiectomy or gonadotropin-releasing hormone [GnRH] analog plus flutamide) as initial therapy and 11 (31%) were started on monotherapy alone. Patients who had not undergone a previous orchiectomy were continued on the GnRH analog. Patients were monitored clinically and with serial PSA measurements, radionuclide scans, and radiographs as indicated to assess response. RESULTS Considering the 35 patients with increasing PSA values, 10 (29%) showed a significant decline (&gt; or = 80% in seven, and &gt; or = 50% in three) in PSA from baseline. All 10 had received combined androgen blockade as initial therapy. The duration of decline was short (median, 5+ months; range, 2 to 10+), but was associated with improvement in clinical symptoms, while one patient had a partial response in an epidural mass with parallel decline in PSA. None of the patients started on single hormone therapies responded. CONCLUSION Discontinuation of flutamide was associated with a significant decrease in PSA values in 10 of 25 patients (40%; 95% confidence interval, 21% to 59%) and clinical improvement in a subset of patients who had an initial response, but later progressive disease on combined androgen blockade. A trial of flutamide withdrawal should be considered in patients progressing on total androgen blockade before the initiation of more toxic therapies. It is likely that flutamide withdrawal has contributed to the observed responses in phase II trials of both second-line hormonal therapies and new cytotoxic agents. Future phase II trials in hormone-refractory prostatic cancer must control for this observation, and insure that progression off flutamide is documented before initiation of alternative treatment.
TREATMENT OF POST-PARTUM HAEMORRHAGE
Authors: W. H. Cory
Journal: BMJ (1907)

Among the various accidents and emergencies which a medical man has to treat, few make more demand upon his readiness and resource than does the occurrence of serious post-partum haemorrhage.It may not often happen, nay, in well managed labours it is a very rare event, hut its very rarity makes individual ex-