tbuckley/cabot-search huggingface dataset:
Assessing Individual Risk for Prostate Cancer
Authors: Robert K. Nam, Ants Toi, Laurence H. Klotz, John Trachtenberg, Michael A.S. Jewett, Sree Appu, D. Andrew Loblaw, Linda Sugar, Steven A. Narod, Michael W. Kattan
Journal: Journal of Clinical Oncology (2007)

To construct a clinical nomogram instrument to estimate individual risk for having prostate cancer (PC) for patients undergoing prostate specific antigen (PSA) screening, using all risk factors known for PC.We conducted a cross-sectional study of 3,108 men who underwent a prostate biopsy, including a subset of 408 volunteers with normal PSA levels. Factors including age, family history of PC (FHPC), ethnicity, urinary symptoms, PSA, free:total PSA ratio, and digital rectal examination (DRE) were incorporated in the model. A nomogram was constructed to assess risk for any and high-grade PC (Gleason score >or= 7).Of the 3,108 men, 1,304 (42.0%) were found to have PC. Among the 408 men with a normal PSA (< 4.0 ng/mL), 99 (24.3%) had PC. All risk factors were important predictors for PC by multivariate analysis (P, .01 to .0001). The area under the curve (AUC) for the nomogram in predicting cancer, which included age, ethnicity, FHPC, urinary symptoms, free:total PSA ratio, PSA, and DRE, was 0.74 (95% CI, 0.71 to 0.81) and 0.77 (95% CI, 0.74 to 0.81) for high-grade cancer. This was significantly greater than the AUC that considered using the conventional screening method of PSA and DRE only (0.62; 95% CI, 0.58 to 0.66 for any cancer; 0.69; 95% CI, 0.65 to 0.73 for high-grade cancer). From receiver operating characteristic analysis, risk factors including age, ethnicity, FHPC, symptoms, and free:total PSA ratio contributed significantly more predictive information than PSA and DRE.In a PC screening program, it is important to consider age, family history of PC, ethnicity, urinary voiding symptoms, and free:total PSA ratio, in addition to PSA and DRE.
The Possible Protective Role of Glucagon-Like Peptide 1 on Endothelium During the Meal and Evidence for an “Endothelial Resistance” to Glucagon-Like Peptide 1 in Diabetes
Authors: Antonio Ceriello, Katherine Esposito, Roberto Testa, Anna Rita Bonfigli, Maurizio Marra, Dario Giugliano
Journal: Diabetes Care (2011)

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion. However, GLP-1 also improves endothelial function in diabetes.Sixteen type 2 diabetic patients and 12 control subjects received a meal, an oral glucose tolerance test (OGTT), and two hyperglycemic clamps, with or without GLP-1. The clamps were repeated in diabetic patients after 2 months of strict glycemic control.During the meal, glycemia, nitrotyrosine, and plasma 8-iso prostaglandin F2α (8-iso-PGF2a) remained unchanged in the control subjects, whereas they increased in diabetic patients. Flow-mediated vasodilation (FMD) decreased in diabetes, whereas GLP-1 increased in both groups. During the OGTT, an increase in glycemia, nitrotyrosine, and 8-iso-PGF2a and a decrease in FMD were observed at 1 h in the control subjects and at 1 and 2 h in the diabetic patients. In the same way, GLP-1 increased in both groups at the same levels of the meal. During the clamps, in both the control subjects and the diabetic patients, a significant increase in nitrotyrosine and 8-iso-PGF2a and a decrease in FMD were observed, effects that were significantly reduced by GLP-1. After improved glycemic control, hyperglycemia during the clamps was less effective in producing oxidative stress and endothelial dysfunction and the GLP-1 administration was most effective in reducing these effects.Our data suggest that during the meal GLP-1 can simultaneously exert an incretin effect on insulin secretion and a protective effect on endothelial function, reasonably controlling oxidative stress generation. The ability of GLP-1 in protecting endothelial function seems to depend on the level of glycemia, a phenomenon already described for insulin secretion.
Review of Evidence-Based Support for Pretreatment Imaging in Melanoma
Authors: Michael S. Sabel, Sandra L. Wong
Journal: Journal of the National Comprehensive Cancer Network (2009)

When making a new diagnosis of melanoma, clinicians often obtain imaging studies to rule out clinically occult distant disease. These studies range from inexpensive tests, such as chest radiographs, to more expensive studies, such as PET/CT. The impetus for ordering these studies is usually the desire to identify potentially resectable distant disease, avoid surgery when curative resection is not possible, and assuage patient anxiety by showing that no evidence of distant disease is present. However, some detrimental aspects to these studies are less apparent, including cost and potential for false-positive findings. Although routine use seems reasonable, the true benefit of these studies depends on the probability of clinically occult disease being present, likelihood that disease will be detected with the available technology, and impact of earlier detection on outcome. Contrary to current practice patterns, available evidence suggests that preoperative imaging studies are associated with significant costs and minimal benefit in most patients with melanoma. This article reviews available literature on the role of pretreatment imaging in patients with newly diagnosed cutaneous melanoma.
The role of superoxide anion generation in phagocytic bactericidal activity. Studies with normal and chronic granulomatous disease leukocytes.
Authors: R B Johnston, B B Keele, H P Misra, J E Lehmeyer, L S Webb, R L Baehner, K V RaJagopalan
Journal: Journal of Clinical Investigation (1975)

The capacity of human phagocytes to generate superoxide anion (O2-), a free radical of oxygen, and a possible role for this radical or its derivatives in the killing of phagocytized bacteria were explored using leukocytes from normal individuals and patients with chronic granulomatous disease (CGD). Superoxide dismutase, which removes O2-, consistently inhibited phagocytosis-associated nitroblue tetrazolium (NBT) reduction indicating the involvement of O2- in this process. Similarly, superoxide dismutase inhibited the luminescence that occurs with phagocytosis, implicating O2- in this phenomenon, perhaps through its spontaneous dismutation into singlet oxygen. Subcellular fractions from homogenates of both normal and CGD leukocytes generated O2- effectively in the presence of NADH as substrate. However, O2- generation by intact cells during phagocytosis was markedly diminished in nine patients with CGD. Leukocytes from mothers determined to be carriers of X-linked recessive CGD by intermediate phagocytic reduction of NBT elaborated O2- to an intermediate extent, further demonstrating the interrelationship between NBT reduction and O2- generation in phagocytizing cells. Activity of superoxide dismutase, the enzyme responsible for protecting the cell from the damaging effects of O2-, was approximately equal in homogenates of normal and CGD granulocytes. Polyacrylamide electrophoresis separated this activity into a minor band that appeared to be the manganese-containing superoxide dismutase associated with mitochondria and a more concentrated, cyanide-sensitive, cytosol form of the enzyme with electrophoretic mobility that corresponded to that of erythrocyte cuprozinc superoxide dismutase. Superoxide dismutase inhibited the phagocytic killing of Escherichia coli, Staphylococcus aureus, and Streptococcus viridans. A similar inhibitory effect was noted with catalase which removes hydrogen peroxide. Neither enzyme inhibited the ingestion of bacteria. Peroxide and O2- are believed to interact to generate the potent oxidant, hydroxyl radical (.OH). A requirement for .OH in the phagocytic bactericidal event might explain the apparent requirement for both O2- and H2O2 for such activity. In agreement with this possibility, benzoate and mannitol, scavengers of .OH, inhibited phagocytic bactericidal activity. Generation of singlet oxygen from O2- and .OH also might explain these findings. It would seem clear from these and other studies that the granulo cyte elaborates O2- as a concomitant of the respiratory burst that occurs with phagocytosis. To what extent the energy inherent in O2- is translated into microbialdeath through O2- itself, hydrogen peroxide, .OH, singlet oxygen, or some other agent remains to be clearly defined.
Activities of antistaphylococcal antibiotics towards the extracellular and intraphagocytic forms of Staphylococcus aureus isolates from a patient with persistent bacteraemia and endocarditis
Authors: S. Lemaire, K. Kosowska-Shick, K. Julian, P.M. Tulkens, F. Van Bambeke, P.C. Appelbaum
Journal: Clinical Microbiology and Infection (2008)
Indoor rock climbing: who gets injured?
Authors: D M Wright, T J Royle, T Marshall
Journal: British Journal of Sports Medicine (2001)

To determine the frequency of overuse injury in indoor climbers, the common sites of such injury, and the factors that influence the probability that a climber will have sustained an overuse injury while climbing indoors.A semisupervised questionnaire was used to survey overuse injury in 295 spectators and competitors at the Entre-Prises World Climbing Championships held in Birmingham 3-5 December 1999. Statistical analysis included simple cross tabulations, calculation of odds ratios, and multiple logistic regression to explore the effect of several factors simultaneously.Some 44% of respondents had sustained an overuse injury, 19% at more than one site. The most common site of injury was the fingers. Univariate analysis showed that the probability of having sustained a climbing injury is higher in men (p = 0.009), those who have climbed for more than 10 years (p = 0.006), those who climb harder routes (p<0.0005), and those who boulder or lead more than they top rope (p<0.0005). The relation between lead grade and climbing injury is linear. Multivariate analysis removed the effect of sex as an independent predictor.Many climbers sustain overuse injury. The most at risk are those with the most ability and dedication to climbing. Climbers should be aware of the risk factors that influence injury and be able to spot the signs and symptoms of injury once they occur.
A qualitative systematic review of coasting, a procedure to avoid ovarian hyperstimulation syndrome in IVF patients
Authors: A. Delvigne
Journal: Human Reproduction Update (2002)

'Coasting', a method which consists of stopping exogenous gonadotrophins and postponing HCG administration until the patient's serum estradiol (E2) level decreases, is often used to prevent ovarian hyperstimulation syndrome (OHSS). We conducted a systematic review to analyse whether there is sufficient evidence to justify the general acceptance of coasting. The studies, which involved 493 patients in 12 studies, are very heterogeneous in the characteristics and number of patients in the ovulation stimulation schemes. The study designs, control groups, selection criteria for coasting and the OHSS classifications were variable. In most studies a threshold value of E2 was used (often 3000 pg/ml) and/or the number of follicles were considered. The fertilization rates (36.7–71%) and the pregnancy rates (20–57%) were acceptable in terms of IVF results in comparison with those of other large IVF databanks. In 16% of the cycles, ascites was described and 2.5% of the patients required hospitalization. In conclusion, while coasting does not avoid totally the risk of OHSS, it decreases its incidence in high-risk patients. Many questions remain unanswered about how coasting should be managed, and we suggest that a randomized prospective multicentre study is required.
Bias Correction Methods Explain Much of the Variation Seen in Breast Cancer Risks of <i>BRCA1/2</i> Mutation Carriers
Authors: Janet R. Vos, Li Hsu, Richard M. Brohet, Marian J.E. Mourits, Jakob de Vries, Kathleen E. Malone, Jan C. Oosterwijk, Geertruida H. de Bock
Journal: Journal of Clinical Oncology (2015)

Recommendations for treating patients who carry a BRCA1/2 gene are mainly based on cumulative lifetime risks (CLTRs) of breast cancer determined from retrospective cohorts. These risks vary widely (27% to 88%), and it is important to understand why. We analyzed the effects of methods of risk estimation and bias correction and of population factors on CLTRs in this retrospective clinical cohort of BRCA1/2 carriers.The following methods to estimate the breast cancer risk of BRCA1/2 carriers were identified from the literature: Kaplan-Meier, frailty, and modified segregation analyses with bias correction consisting of including or excluding index patients combined with including or excluding first-degree relatives (FDRs) or different conditional likelihoods. These were applied to clinical data of BRCA1/2 families derived from our family cancer clinic for whom a simulation was also performed to evaluate the methods. CLTRs and 95% CIs were estimated and compared with the reference CLTRs.CLTRs ranged from 35% to 83% for BRCA1 and 41% to 86% for BRCA2 carriers at age 70 years width of 95% CIs: 10% to 35% and 13% to 46%, respectively). Relative bias varied from -38% to +16%. Bias correction with inclusion of index patients and untested FDRs gave the smallest bias: +2% (SD, 2%) in BRCA1 and +0.9% (SD, 3.6%) in BRCA2.Much of the variation in breast cancer CLTRs in retrospective clinical BRCA1/2 cohorts is due to the bias-correction method, whereas a smaller part is due to population differences. Kaplan-Meier analyses with bias correction that includes index patients and a proportion of untested FDRs provide suitable CLTRs for carriers counseled in the clinic.
Platelet <sup>3</sup>H‐Serotonin Releasing Immune Complexes Induced by <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis
Authors: H. Permin, P. Stahl Skov, S. Norn, N. Høiby, P. O. Schiøtz
Journal: Allergy (1982)

In vitro formation of immune complexes was studied by 3 H‐serotonin release from human platelets by P. aeruginosa antigens in the presence of serum From 22 cystic fibrosis patients. chronically infected with mucoid P. aeruginosa (CF + P) and with a pronounced antibody response against these bacteria, and in 24 patients without P. aeruginosa (CF‐P). All CF + P patients responded with 3 H ‐serotonin release (16–34%), whereas CF‐P patients released less than 15%. In the group of CF4‐P patients the number of P. aeruginosa precipitins was correlated to the serotonin liter. Time courses indicated that SH‐serotonin release was maximal between 2 and 5 min, and that no further release was observed up to 20 min. There was a gradual increase in 3 H ‐serotonin release with higher platelet concentrations The response was not changed by complement inactivation. and fractionation of serum demonstrated that the serotonin release was dependent on the presence of the immuno‐globulin fraction. These experiments support the suggestion of a type 111 reaction being invoked in the lung damage in CF + P patients and also suggest a possible involvement of serotonin in the inflammatory reaction during chronic P. aeruginosa lung infection.
Somatostatin inhibits the effect of secretin on bile flow and on hepatic bilirubin transport in the rat.
Authors: G L Ricci, J Fevery
Journal: Gut (1989)

Increasing amounts of porcine secretion (0.05 to 2.00 clinical units/h/100 g body wt) given to rats during a continuous infusion of bilirubin, increased bile flow and the apparent maximal biliary excretion of bilirubin (9Tm9). This increment was caused by an enhanced biliary output of bilirubin monoconjugates. The effect was dose dependent but maximal at a secretin infusion of 0.80 CU. Somatostatin 0.2 and 0.8 microgram/h/100 g body wt caused a dose related inhibition of the hepatic effects of secretin both on bile flow and on biliary output of bilirubin conjugates. As secretin elicits the release of somatostatin, a feed-back system could be envisaged whereby the somatostatin released stops the effects of secretin.
Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis: report of five cases and review of published reports.
Authors: M R Hargreaves, A G Mowat, M K Benson
Journal: Thorax (1992)

BACKGROUND: Low dose methotrexate has become established in the treatment of refractory rheumatoid arthritis. Until recently it has been considered that the use of a low dose regimen (&lt; 20 mg/week) would avoid the pulmonary toxicity associated with the higher doses prescribed in malignant disease. Although initial experience with low dose methotrexate was encouraging, an increasing number of cases of an acute, life threatening pneumonitis are being reported in patients with refractory rheumatoid arthritis. PATIENTS: Since 1984 43 patients with refractory rheumatoid arthritis have been established on low dose methotrexate in the Oxford Health District. Five of these patients have subsequently developed acute methotrexate induced pneumonitis. The clinical and radiological features of these cases are described and previous reports reviewed. RESULTS: Five patients having low dose methotrexate treatment developed acute pneumonitis. Presentation was subacute and dominated by constitutional features. Respiratory symptoms developed insidiously but progressed rapidly with increasing dyspnoea associated with severe hypoxia. Chest radiographs were non-specific, showing diffuse interstitial infiltration and alveolar shadowing. Microbiological investigation gave negative results. In all cases methotrexate was discontinued and high dose corticosteroids started, with rapid clinical and radiological improvement. After withdrawal of steroid both clinical and radiological resolution was maintained at follow up. CONCLUSION: Acute pneumonitis is an uncommon but serious adverse effect of low dose methotrexate treatment for refractory rheumatoid arthritis. The initial presentation is non-specific and a high index of suspicion is required as respiratory failure may develop rapidly. Management depends on exclusion of infection, withdrawal of methotrexate, and high dose corticosteroid treatment. Full supportive treatment is indicated as the prognosis in such patients is good.
Effects of potassium on isolated canine coronary arteries. Modulation of adrenergic responsiveness and release of norepinephrine.
Authors: L Borda, R Shuchleib, P D Henry
Journal: Circulation Research (1977)

We studied effects of changes in the extracellular potassium concentration (|K* ]") on the mechanical responsiveness of canine coronary artery preparations.Four different contractile behaviors were delineated between | K *),, = 0 and 40 HIM: (1) at [K + ] o < 1 mu, a contracture developed which was augmented by /3-adrenergic stimulation and inhibited by propranolol, 1 x 10~7M; (2) at |K*| (I between 1 and 2.5 mti, arterial tone was minimum and propranolol acted as a potent constrictor.Within this range of [K + ],,, arteries exhibited calciuminduced relaxations and verapamil-induced contractions; (3) at |K* |,, between 5 and 15 mM there was a steep rise in force which was increased by isoproterenol (/3-adrenergic contraction), almost completely blocked by L-propranolol, but not attenuated by a-adrenergic blockade with phentolamine; (4) at |K' ]« > 30 mM, effects of /3-adrenergic stimulation and blockade became very small.Steady increases in force elicited by isoproterenol and by sudden increases in [K + ] o were preceded by transient relaxations.Effects of exogenous and endogenous (tyramine, nerve stimulation) norepinephrine paralleled those of isoproterenol and were blocked by propranolol but not attenuated by phentolamine.In contrast, modulation of the effects of phenylephrine by potassium consisted of monotonicaUy increasing constrictor responses over the whole range of |K'| 0 tested.Arteries labeled with ( 3 H)-norepinephrine showed substantial changes in ( 3 H)-efTlux with relatively small changes in [K + ] o .Maximum releases were observed with |K* I,, ranging between 10 and 25 mM.The smallest releases were observed at the highest (K + | o (40 mM).Thus, changes in [K + ] o influence arterial tone by modulating or-and /3-adrenergic effects and by regulating the release of neurotransmitter from the coronary nerves.IT IS generally accepted that acute myocardial ischemia and hypoxia result in acute coronary vasodilation. 1However, effects of prolonged ischemia on coronary vascular tone have been less well defined. 2In conscious dogs subjected to acute coronary ligation, collateral flow may increase substantially after a few hours of ischemia, suggesting that dynamic factors may limit effective collateral perfusion temporarily. 3-4 One possible pathophysiological mechanism is that prolonged ischemia may lead to coronary arterial constriction.Among the vasoactive substances that are released from the ischemic myocardium
Sleep disturbance in adults with cancer: a systematic review of evidence for best practices in assessment and management for clinical practice
Authors: D. Howell, T.K. Oliver, S. Keller-Olaman, J.R. Davidson, S. Garland, C. Samuels, J. Savard, C. Harris, M. Aubin, K. Olson, J. Sussman, J. MacFarlane, C. Taylor
Journal: Annals of Oncology (2013)
Activation of ischemia- and reperfusion-sensitive abdominal visceral C fiber afferents. Role of hydrogen peroxide and hydroxyl radicals.
Authors: G L Stahl, H L Pan, J C Longhurst
Journal: Circulation Research (1993)

Abdominal ischemia and reperfusion evoke reflex excitation of the cardiovascular system and generate reactive oxygen species. We have shown previously that the reactive oxygen species hydrogen peroxide (H2O2) elicits reflex excitation of the cardiovascular system after serosal application to abdominal organs. However, it is not known if ischemia-sensitive afferents respond to reactive oxygen species or if scavengers such as dimethylthiourea (DMTU) inhibit the response of these afferents to ischemia or reperfusion. Therefore, to provide more information on the neurophysiological mechanisms underlying the activation of these afferents, we studied their responses to H2O2 applied to the receptive field during recordings of single-unit activity of ischemia-insensitive or -sensitive abdominal visceral C fiber afferents in anesthetized cats. Additionally, we recorded single-unit activity of ischemia and reperfusion-sensitive afferents before and after treatment with DMTU (10 mg/kg), which scavenges H2O2 and hydroxyl radicals or the iron chelator deferoxamine (DEF, 10 mg/kg), which inhibits hydroxyl radical formation. Application of 44 mumol H2O2 to afferent endings increased the discharge frequency in nine of 11 ischemia-sensitive units, from 0.01 +/- 0.01 to 0.67 +/- 0.16 impulses per second. In contrast, only one of 10 ischemia-insensitive C fibers responded to H2O2 application. In an additional 13 ischemia-sensitive C fibers, DMTU significantly (p &lt; 0.05) attenuated ischemia-induced increases in discharge frequency from 0.42 +/- 0.18 to 0.24 +/- 0.1 impulses per second (ischemia versus DMTU + ischemia, respectively). In eight additional C fibers, we found that reperfusion after 5 minutes of ischemia was associated with an increase in discharge activity from a baseline activity of 0.02 +/- 0.01 to 0.44 +/- 0.07 impulses per second. DMTU significantly attenuated the reperfusion-induced increases in discharge frequency from 0.08 +/- 0.04 to 0.18 +/- 0.06 impulses per second. DEF significantly (p &lt; 0.05) attenuated the increased discharge activity from 0.39 +/- 0.07 to 0.10 +/- 0.04 impulses per second (ischemia versus DEF + ischemia, respectively) in an additional 11 ischemia-sensitive C fibers. In contrast, iron-saturated DEF did not attenuate ischemia- and reperfusion-induced increases in impulse activity. Thus, ischemia-sensitive but not ischemia-insensitive abdominal visceral afferents respond to H2O2. Furthermore, ischemia- and reperfusion-sensitive afferents decreased their impulse activity to a repeated period of ischemia or reperfusion after DMTU or DEF treatment. These data suggest that reactive oxygen species, particularly H2O2 and hydroxyl radicals, activate abdominal visceral C fibers in the cat during brief periods of ischemia and reperfusion.