tbuckley/cabot-search huggingface dataset:
Microvessel Density and Distribution in Ductal Carcinoma In Situ of the Breast
Authors: A. J. Guidi, L. Fischer, J. R. Harris, S. J. Schnitt
Journal: JNCI Journal of the National Cancer Institute (1994)

Background : Prior studies have suggested that microvessel density is an important prognostic factor in invasive breast cancer. However, the extent and distribution of microvessels in association with ductal carcinoma in situ (DCIS) have not been well defined. Purpose : Our goal was to determine the density and distribution of stromal microvessels in DCIS and to investigate the relationships among microvessel density, histopathologic features, HER2/neu oncogene expression, and tumor proliferation rate. Methods : Of 61 consecutive cases of DCIS identified from hospital pathology reports, 55 cases were evaluated. Breast biopsy specimens had been preserved in paraffin blocks for each DCIS case. Histologic sections of formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin and immunostained for factor VIII-related antigen, the HER2/neu oncoprotein, and the proliferative-associated antigen detected by the Ki-Sl antibody. Factor VIII-stained sections from each case were independently examined by two pathologists and overall tumor-associated stromal microvessel density was scored semiquantitatively on a 1+ to 3+ scale by each observer. Quantitative microvessel counts of DCIS-associated stromal microvessel density were performed. The presence or absence of a cuff of microvessels in immediate apposition to the basement membrane of involved spaces was also evaluated. Results : A variable number of microvessels were found to be present in a diffuse pattern surrounding spaces involved with DCIS. Semiquantitative microvessel scores were 2+ in the majority of cases (53%); 22% of cases were 1+, and 25% were 3+. Quantitative microvessel counts ranged from 17 to 80 vessels per 100× field (0.45 mm 2 ), with a mean ± SD of 42.9 ± 16.6. Comedo-type lesions were significantly ( P =.004) more often associated with 3+ microvessel density than non-comedo-type lesions by semiquantitative assessment. As determined by both semiquantitative and quantitative analysis, respectively, the presence of prominent microvessel density was significantly associated with marked stromal desmoplasia ( P =.05 and P =.04), HER2/neu expression ( P =.03 and P =.0002), and high Ki-S1 proliferation index ( P =.05 and P =.01). Vascular cuffing around involved spaces was identified in 21 of the 55 cases (38%) and was not significantly associated with histologic features, HER2/neu expression, or Ki-S1 proliferation index. Conclusions : DCIS of the breast is characterized by two patterns of stromal microvessels. The first pattern is a diffuse increase in stromal microvessels surrounding involved spaces. This pattern is particularly prominent in comedo-type lesions with marked stromal desmoplasia. The second pattern is microvessel cuffing of involved spaces that is present in only a minority of cases and appears unrelated to histologic features evaluated, including DCIS subtype. [J Nat Cancer Inst 86: 614–619, 1994]
Early life risk factors for obesity in childhood: cohort study
Authors: John J Reilly, Julie Armstrong, Ahmad R Dorosty, Pauline M Emmett, A Ness, I Rogers, Colin Steer, Andrea Sherriff
Journal: BMJ (2005)

To identify risk factors in early life (up to 3 years of age) for obesity in children in the United Kingdom.Prospective cohort study.Avon longitudinal study of parents and children, United Kingdom.8234 children in cohort aged 7 years and a subsample of 909 children (children in focus) with data on additional early growth related risk factors for obesity.Obesity at age 7 years, defined as a body mass index (3) 95th centile relative to reference data for the UK population in 1990.Eight of 25 putative risk factors were associated with a risk of obesity in the final models: parental obesity (both parents: adjusted odds ratio, 10.44, 95% confidence interval 5.11 to 21.32), very early (by 43 months) body mass index or adiposity rebound (15.00, 5.32 to 42.30), more than eight hours spent watching television per week at age 3 years (1.55, 1.13 to 2.12), catch-up growth (2.60, 1.09 to 6.16), standard deviation score for weight at age 8 months (3.13, 1.43 to 6.85) and 18 months (2.65, 1.25 to 5.59); weight gain in first year (1.06, 1.02 to 1.10 per 100 g increase); birth weight, per 100 g (1.05, 1.03 to 1.07); and short (< 10.5 hours) sleep duration at age 3 years (1.45, 1.10 to 1.89).Eight factors in early life are associated with an increased risk of obesity in childhood.
Two drugs show promising results for treating hyperkalemia in US study
Authors: J. Wise
Journal: BMJ (2015)

The UDP-glucuronosyltransferase (UGT) enzymes are critical for regulating nutrients, hormones, and endobiotics, as well as for detoxifying xenobiotics. Human and murine fetuses are known to express glucuronidation enzymes, but there are currently no data prior to implantation. Here we addressed this gap in knowledge and tested whether Ugt enzymes are already present in preimplantation-stage embryos. Blastocysts were obtained after in vitro fertilization with gametes from B6D2F1 hybrid mice and from embryo culture. Protein expression and localization were determined using pan-specific UGT1A and UGT2B, as well as anti-human isoform-specific antibodies. Immunofluorescence analysis showed that blastocysts expressed Ugt1a globally, in the cytoplasm and nuclei of all of the cells. Western blots demonstrated the presence of Ugt1a6 but not Ugt1a1, Ugt1a3, Ugt1a4, or Ugt1a9. The Ugt2b proteins were not detected by either assay. The level of Ugt activity in murine blastocysts was comparable with that of the adult human liver (per milligram of protein), but the activity of <i>β</i>-glucuronidase, an Ugt-partnering enzyme responsible for substrate regeneration, was lower. Altogether, these data confirm that Ugt1a proteins are present and active in preimplantation murine embryos and point to a potential role for these proteins in implantation and early embryonic and fetal development.
Patterns of quantitative food‐specific IgE‐antibodies and reported food hypersensitivity in 4‐year‐old children
Authors: E. Östblom, G. Lilja, S. Ahlstedt, M. Van Hage, M. Wickman
Journal: Allergy (2007)

Diagnosis of food hypersensitivity (FHS) is difficult and interpretation of food allergy tests is complicated.To investigate the probability of reported FHS in relation to levels of food-specific IgE-antibodies (AB) in a population-based setting of 4-year-old children (n = 2336).Information on FHS was obtained from a questionnaire and specific IgE-AB to milk, egg, fish, peanut, soy and wheat were analysed.Thirty-one per cent of the children with reported FHS (n = 284) were sensitized (> or =0.35 kU(A)/l) to at least one of the tested foods compared with 11% of children without FHS (n = 2052). Furthermore, the probability of reported symptoms to milk, egg and fish increased with increasing levels of food-specific IgE-AB to the same food allergens. A similar trend was seen for peanut and wheat, but not for soy. Increasing levels of specific IgE-AB to milk or egg were also associated with an increasing risk of reported symptoms caused by other foods.Quantitative measurements of IgE-AB to milk, egg and fish are useful to evaluate IgE-associated FHS in preschool children also in a population based sample. Such measurements appear to be of limited value for soy bean and wheat, in particular as a screening method.
Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia
Authors: Amy Holleman, Monique L. den Boer, Karin M. Kazemier, H. Berna Beverloo, Anne R. M. von Bergh, Gritta E. Janka-Schaub, Rob Pieters
Journal: Blood (2005)
Search for a retroviral cause for sarcoidosis: no evidence from peripheral blood studies
Authors: DJ Lyons, A Sinclair, HG Smith, DN Mitchell, AG Dalgleish
Journal: European Respiratory Journal (1991)

Twenty six patients with sarcoidosis of recent onset or with severe progressive disease were studied for evidence of retroviral infection. Peripheral blood mononuclear cells (PBMC) were cultured in vitro and stimulated with phytohaemagglutinin and interleukin-2. Induction of syncytia (SI) and production of reverse transcriptase (RT) were sought as indicators of possible retroviral infection. PBMC from two patients showed syncytia formation and in one of these two there was associated production of low levels of reverse transcriptase. The remaining patients showed neither RT nor SI activity. The predominantly negative results of this study indicate that sarcoidosis is unlikely to be of retroviral aetiology; however, cell populations from sites of active disease should be studied before drawing this conclusion.
Cardiorespiratory fitness, pulmonary function and C-reactive protein levels in adults with diabetes
Authors: Cristina Oliveira Francisco, Aparecida Maria Catai, Silvia C.G. Moura, Sérgio L.B. Lopes, Adriano M. Del Vale, Angela M.O. Leal
Journal: European Respiratory Journal (2012)

Background/Aim: Diabetes Mellitus (DM) is associated with impairment of cardiorespiratory fitness and pulmonary function; increasing evidences have suggested that comorbidities and systemic inflammation may be involved. The objective of this study was evaluate changes in metabolic variables, C-reactive protein (CRP) levels, cardiorespiratory fitness and pulmonary function in DM patients compared with healthy subjects. Methods: 19 men with diabetes (49±2 years) and 19 healthy control subjects (51±1 years) were studied. All subjects performed a spirometry and an incremental cardiopulmonary exercise test on a cycloergometer with electromagnetic breaking (workload increases, range 13-22W/min). Cardiopulmonary data were continuously collected with a metabolic unit. Heart rate (HR) was continuously monitored. Results: are presented in table 1.  Conclusion: The cardiorespiratory fitness is reduced in patients with diabetes but the spirometric values are preserved, and the CRP did not differ of the control subjects.  Financial support: Capes, FAPESP.
Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: A placebo-controlled trial
Authors: Thomas Berg, Bernd Kronenberger, Holger Hinrichsen, Tilman Gerlach, Peter Buggisch, Eva Herrmann, Ulrich Spengler, Tobias Goeser, Samer Nasser, Karsten Wursthorn, Gerd R. Pape, Uwe Hopf, Stefan Zeuzem
Journal: Hepatology (2003)

The antiviral efficacy of amantadine in patients with chronic hepatitis C is controversial. In this randomized, prospective, placebo–controlled, multicenter trial, triple therapy with interferon alfa (IFN–α)–2a plus ribavirin and amantadine (amantadine group) was compared with combination therapy IFN–α plus ribavirin (control group). Four hundred previously untreated patients with histologically proven chronic hepatitis C were randomly allocated to treatment with amantadine sulphate (100 mg twice daily orally) or a matched placebo together with IFN–α induction plus ribavirin (1,000–1,200 mg/day orally) for 48 weeks. The primary end point was sustained virologic response (SVR) defined as undetectable serum hepatitis C virus (HCV) RNA (&lt;100 copies/mL) 24 weeks after the end of treatment. SVR was observed in 52% of the amantadine group and in 43.5% of the control group ( P = .11). Among patients with HCV genotype 1 infection, the corresponding SVR rates were 39% and 31%, respectively. The virologic on–treatment response rate in week 24 was significantly higher in the amantadine group as compared with the control group (70% vs. 59%, respectively, P = .016). This beneficial effect was mainly related to HCV type 1–infected patients (63% vs. 47%, respectively, P = .012). Independent factors associated with SVR, according to multiple logistic regression analysis, were amantadine treatment, low baseline HCV RNA, platelet counts (≥250/nL), pretreatment ALT quotient ≥3, and GGT level (&lt;28 U/L) as well as HCV genotypes other than 1. In conclusion, although we could not demonstrate a significant advantage of the triple regimen in univariate analysis, multivariate analysis offers arguments that amantadine should be considered as a potential anti–HCV drug in future studies.
THE PSYCHIATRIST IN GROUP MEDICAL PRACTICE
Authors: J. E. TYLER, TOM R. TURNER
Journal: American Journal of Psychiatry (1952)

1. During the past 10 years there has been a marked increase in the number of psychiatrists in group medical clinics, the number of such clinics having psychiatrists having doubled since 1946. 2. Although there is reluctance on the part of many clinics to add psychiatrists to their medical staffs, the psychiatrist has demonstrated his value to those group clinics with psychiatric departments, as indicated by the fact that one-third of such clinics have shown an increase in the size of this department. 3. The benefits to the patient resulting from the association of a psychiatrist in a group medical clinic are discussed. Such an association enables the psychiatrist and his medical colleagues to utilize the medical skills of each other in offering over-all medical care to the patient. 4. The psychiatrist in the group medical clinic is in an excellent position to counteract some of the negative feelings held by medicine in regard to his specialty and to further the integration of his specialty into the whole of medical practice.
Incontinentia Pigmenti (Bloch-Sulzberger)
Authors: A. P. Roberts
Journal: BMJ (1958)

INFUSIONSW (l953), Brande et al. (1953), McEntegwt (1956), and thers after the trassfusion of contaminated blood.The blood in those ca: wa contamninatd by cold-rowing micro- orpanisms, most of them.Grain-negative-The effet of emdotoxias of Gram-negative baceria have been extensively stuied in animals.The main manifestations-were fever, diarrhoea and vomiting, hypoglycaemia, changes in leuco- cyte distbutio, and shock, resulting im death.Ebert et al.(1955) injected meningococu toxins intravenously into dog, prodcing a preciptous fall in blood preure.They cocluded thal this wa due to venous pooling of the blood in the viscera.The shock ras treated successfully with noradrenaline.Augmentation of the blood volume was less effective, and cortisone was of no kelp.Weit et al. (1956) produced shock in dog with coNi endotoxin.They also
Preoperative apolipoprotein CI levels correlate positively with the proinflammatory response in patients experiencing endotoxemia following elective cardiac surgery
Authors: Emile F. Schippers, Jimmy F. P. Berbée, Inge M. van Disseldorp, Michael I. M. Versteegh, Louis M. Havekes, Patrick C. N. Rensen, Jaap T. van Dissel
Journal: Intensive Care Medicine (2008)

Experimental models show that apolipoprotein CI (apoCI) binds and enhances the inflammatory response to endotoxin. We studied in patients undergoing cardiopulmonary bypass surgery (CPB) and experiencing endotoxemia during reperfusion whether plasma apoCI levels correlate with the inflammatory response and perioperative cytokine release.Prospective, observational, clinical cohort study.Operating room (OR) and intensive care unit (ICU) of a university hospital.One hundred fifty-nine consecutive patients > 18 years of age (66% males =105), median age 65 and 67 years for males and females, respectively) undergoing elective cardiothoracic surgery with cardiopulmonary bypass.None.Baseline apoCI, apoCIII, total cholesterol and triglyceride levels, and perioperative endotoxin and TNF-alpha levels were determined.High preoperative plasma apoCI, but not apoCIII, levels were associated (p < 0.05) with increased perioperative levels of TNF-alpha in patients experiencing endotoxemia. This association was not observed in patients without endotoxemia.High plasma apoCI is positively related to proinflammatory response in patients experiencing endotoxemia and confirms the observations in animal models.
Incidence and risk factors of running-related injuries during preparation for a 4-mile recreational running event
Authors: I Buist, S W Bredeweg, B Bessem, W van Mechelen, K A P M Lemmink, R L Diercks
Journal: British Journal of Sports Medicine (2008)

Objective In this study, the incidence and the sex-specific predictors of running-related injury (RRI) among a group of recreational runners training for a 4-mile running event were determined and identified, respectively. Design Prospective cohort study. Methods Several potential risk factors were prospectively measured in 629 novice and recreational runners. They were observed during an 8-week training period for any running-related musculoskeletal injuries of the lower limbs and back. A running-related injury was defined as any musculoskeletal pain of the lower limb or back causing a restriction of running for at least 1 day. Results At least one RRI was reported by 25.9% of the runners during the 8-week observation period. The incidence of RRI was 30.1 (95% CI 25.4 to 34.7) per 1000 h of running exposure. Multivariate Cox regression showed that male participants were more prone to sustain a RRI than female participants (HR 1.4; 95% CI 1.0 to 2.0). No previous running experience was the most important risk factor in male (HR 2.6; 95% CI 1.2 to 5.5) and female (HR 2.1; 95% CI 1.2 to 3.7) participants. Conclusions The incidence of running-related injuries in recreational runners preparing for a 4-mile running event is substantially high. Male and female participants have different risk profiles. Furthermore, the findings suggest that novice runners may benefit the most out of preventive interventions for RRI.
Biologic sequelae of IκB kinase (IKK) inhibition in multiple myeloma: therapeutic implications
Authors: Teru Hideshima, Dharminder Chauhan, Tanyel Kiziltepe, Hiroshi Ikeda, Yutaka Okawa, Klaus Podar, Noopur Raje, Alexei Protopopov, Nikhil C. Munshi, Paul G. Richardson, Ruben D. Carrasco, Kenneth C. Anderson
Journal: Blood (2009)
Multigene Targeting with Antisense Oligodeoxynucleotides: An Exploratory Study Using Primary Human Leukemia Cells
Authors: Joanna B. Opalinska, Boguslaw Machalinski, Janina Ratajczak, Mariusz Z. Ratajczak, Alan M. Gewirtz
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We previously reported that the c-myb and Vav proto-oncogenes are amenable to silencing with antisense oligodeoxynucleotides and that inhibition of either impairs leukemic cell growth. Because the expression of these genes is not known to be linked, we sought to determine the therapeutic value of silencing both genes simultaneously in K562 and primary patient (n = 9) chronic myelogenous leukemia cells. Experimental Design: K562 and primary chronic myelogenous leukemia cells were exposed to antisense oligodeoxynucleotides (alone or in combination) for 24 or 72 hours and then cloned in methylcellulose cultures. Effects on K562 cluster, and blast-forming unit–erythroid colonies and granulocyte-macrophage colony-forming units were determined and correlated with the ability to down-regulate the targeted mRNA. Results: After 24-hour exposure, K562 cell growth was inhibited in a sequence specific, dose-responsive manner with either c-myb or Vav antisense oligodeoxynucleotides. Exposure to both oligodeoxynucleotides simultaneously considerably enhanced growth inhibition and accelerated apoptosis. Primary cell results were more complex. After 24- and 72-hour exposures to either anti–vav or anti–myb antisense oligodeoxynucleotides, equivalent colony-forming unit inhibition was observed. Exposing cells to both antisense oligodeoxynucleotides simultaneously for 24 hours did not result in additional inhibition of colony formation. However, after 72-hour incubation with both oligodeoxynucleotides, colony formation was diminished significantly when compared with either oligodeoxynucleotides alone (from ∼30% to ∼78% for granulocyte-macrophage colony-forming unit; ∼50% to ∼80% for blast-forming unit–erythroid). Conclusions: We hypothesize that exposing primary leukemic cells to antisense oligodeoxynucleotides targeted to two, or possibly more, genes might significantly augment the therapeutic utility of these molecules.
Raised serum concentrations of pancreatic enzymes in cigarette smokers.
Authors: M A Dubick, C N Conteas, H T Billy, A P Majumdar, M C Geokas
Journal: Gut (1987)

Circulating concentrations of digestive enzymes, certain lysosomal hydrolases and protease inhibitors were measured in 19 heavy smokers and 13 non-smokers before (basal) and at 15, 30, and 60 minutes after a single intravenous injection of secretin (75 CU). In smokers, basal serum amylase and immunoreactive pancreatic elastase 2 (IRE2) concentrations were about 100% and 25% higher respectively, than in the non-smokers, whereas, no differences were observed in basal immunoreactive cationic trypsinogen (IRCT) concentrations and in acid phosphatase and beta-glucuronidase activities between the two groups. Furthermore, a single injection of secretin to cigarette smokers significantly increased serum amylase, IRCT and IRE2 by 155%, 200%, and 100%, respectively when compared with their corresponding basal levels. No such increment was observed in the non-smokers. In addition, there were no significant differences in serum trypsin or elastase inhibitory capacity or immunoreactive alpha 1-protease inhibitor and alpha 2-macroglobulin levels between smokers and non-smokers. The levels and inhibitory capacity of these protease inhibitors was also not affected by secretin injection. These data suggest that cigarette smoking enhances the responsiveness of the exocrine pancreas to a physiological stimulus such as secretin, with resultant substantial increase in the concentrations of pancreatic hydrolases in blood.
Surgical Intervention for Peripheral Arterial Disease
Authors: Shant M. Vartanian, Michael S. Conte
Journal: Circulation Research (2015)

The prevalence of peripheral arterial disease (PAD) is increasing worldwide, with recent global estimates exceeding 200 million people. Advanced PAD leads to a decline in ambulatory function and diminished quality of life. In its most severe form, critical limb ischemia, rest pain, and tissue necrosis are associated with high rates of limb loss, morbidity, and mortality. Revascularization of the limb plays a central role in the management of symptomatic PAD. Concomitant with advances in the pathogenesis, genetics, and medical management of PAD during the last 20 years, there has been an ongoing evolution of revascularization options. The increasing application of endovascular techniques has resulted in dramatic changes in practice patterns and has refocused the question of which patients should be offered surgical revascularization. Nonetheless, surgical therapy remains a cornerstone of management for advanced PAD, providing versatile and durable solutions to challenging patterns of disease. Although there is little high-quality comparative effectiveness data to guide patient selection, existing evidence suggests that outcomes are dependent on definable patient factors such as distribution of disease, status of the limb, comorbid conditions, and conduit availability. As it stands, surgical revascularization remains the standard against which emerging percutaneous techniques are compared. This review summarizes the principles of surgical revascularization, patient selection, and expected outcomes, while highlighting areas in need of further research and technological advancement.