tbuckley/cabot-search huggingface dataset:
Icodextrin Improves the Fluid Status of Peritoneal Dialysis Patients
Authors: Simon J. Davies, Graham Woodrow, Kieron Donovan, Jörg Plum, Paul Williams, Ann Catherine Johansson, Hans-Peter Bosselmann, Olof Heimbürger, Ole Simonsen, Andrew Davenport, Anders Tranaeus, Jose C. Divino Filho
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Worsening fluid balance results in reduced technique and patient survival in peritoneal dialysis. Under these conditions, the glucose polymer icodextrin is known to enhance ultrafiltration in the long dwell. A multicenter, randomized, double-blind, controlled trial was undertaken to compare icodextrin versus 2.27% glucose to establish whether icodextrin improves fluid status. Fifty patients with urine output <750 ml/d, high solute transport, and either treated hypertension or untreated BP >140/90 mmHg, or a requirement for the equivalent of all 2.27% glucose exchanges, were randomized 1:1 and evaluated at 1, 3, and 6 mo. Members of the icodextrin group lost weight, whereas the control group gained weight. Similar differences in total body water were observed, largely explained by reduced extracellular fluid volume in those receiving icodextrin, who also achieved better ultrafiltration and total sodium losses at 3 mo (P < 0.05) and had better maintenance of urine volume at 6 mo (P = 0.039). In patients fulfilling the study's inclusion criteria, the use of icodextrin, when compared with 2.27% glucose, in the long exchange improves fluid removal and status in peritoneal dialysis. This effect is apparent within 1 mo of commencement and was sustained for 6 mo without harmful effects on residual renal function. E-mail: [email protected]
Adrenergic coronary vasoconstriction helps maintain uniform transmural blood flow distribution during exercise.
Authors: A H Huang, E O Feigl
Journal: Circulation Research (1988)

The hypothesis that alpha-adrenergic coronary vasoconstriction helps maintain a uniform transmural distribution of myocardial blood flow during exercise was tested in dogs. Carotid artery loops were surgically constructed and a splenectomy performed three weeks prior to study. On the day of study, the dog was anesthetized briefly (fentanyl and nitrous oxide) for percutaneous catheterization, and alpha-receptors in one myocardial region were blocked with phenoxybenzamine (0.25 mg/kg) infused selectively into the left circumflex coronary artery. Recirculation of phenoxybenzamine was minimized by drainage of coronary sinus outflow during the infusion. After the dog recovered from the anesthesia, regional blood flow was measured at rest and during graded treadmill exercise with the microsphere technique calibrated by reference blood samples. Average transmural flow was limited by alpha-vasoconstriction and was less in the region where alpha-receptors were intact than in the region where they were blocked, as has been described by others. The ratio of inner layer myocardial blood flow to outer layer flow was better maintained in the region with alpha-receptors intact than in the region with alpha-receptors blocked when myocardial oxygen consumption was 150 microliter/min/g or greater (p less than 0.001). Even though average transmural flow was limited by alpha-receptor activation, inner layer myocardial blood flow was greater in the region with alpha-receptors intact than in the region with alpha-receptors blocked when myocardial oxygen consumption was 500 microliter/min/g or more (p less than 0.05). In conclusion, adrenergic coronary vasoconstriction mediated by alpha-receptors helps to maintain a uniform transmural distribution of myocardial blood flow during exercise in spite of limiting average transmural flow.
Physician, Organizational, and Patient Factors Associated With Suboptimal Blood Pressure Management in Type 2 Diabetic Patients in Primary Care
Authors: Carel F. Schaars, Petra Denig, Willeke N. Kasje, Roy E. Stewart, Bruce H.R. Wolffenbuttel, Flora M. Haaijer-Ruskamp
Journal: Diabetes Care (2004)

OBJECTIVE—To assess the quality of hypertension care in patients with type 2 diabetes in general practice and identify physician, organizational, and patient factors associated with suboptimal care. RESEARCH DESIGN AND METHODS—Data from 895 randomly selected diabetic patients were extracted from the electronic medical records of 95 general practitioners. Physician and organizational characteristics were collected with a questionnaire. We conducted a multilevel analysis to identify associations with blood pressure registration, hypertension treatment, and achievement of target blood pressure levels. RESULTS—For 652 patients (73%), a blood pressure measurement was recorded in the last year. Of these patients, 132 (20%) reached a target level of 135/85 mmHg. In total, 595 patients were classified as having hypertension, of whom 192 received no treatment (32%), 193 received an ACE inhibitor (32%), and 210 received other antihypertensives. Patients visiting a diabetes facility, referred to a specialist, with a female general practitioner, or with a general practitioner with ≤10 years work experience had better recordings of their blood pressure. Suboptimal treatment was higher in older patients and smoking patients. Treatment was better in patients with coronary comorbidity, hyperlipidemia, or those referred to a specialist. Not achieving the blood pressure target was related to older age of the patients. CONCLUSIONS—Hypertension management of type 2 diabetic patients in primary care is suboptimal. Characteristics of general practitioners as well as additional care provided by a diabetes facility or a specialist are associated with better processes of care, but blood pressure outcomes are not as clearly related to these factors.
Identification of a Novel 14-3-3ζ Binding Site Within the Cytoplasmic Domain of Platelet Glycoprotein Ibα That Plays a Key Role in Regulating the von Willebrand Factor Binding Function of Glycoprotein Ib-IX
Authors: Yanhong Yuan, Weilin Zhang, Rong Yan, Yi Liao, Lili Zhao, Changgeng Ruan, Xiaoping Du, Kesheng Dai
Journal: Circulation Research (2009)

Rationale: The interaction between platelet glycoprotein (GP) Ib-IX and von Willebrand factor (VWF) is initiated by conformational changes in immobilized VWF and is also regulated by the intraplatelet proteins 14-3-3ζ and filamin A. Both 14-3-3ζ and filamin A associate with the cytoplasmic domain of GPIbα, whereas little is known about their relationship in regulating the VWF binding function of GPIb-IX. Objective: To explore the mechanism underlying the roles of 14-3-3ζ and filamin A in regulating the VWF binding function of GPIb-IX. Methods and Results: A truncation mutant of GPIbα (Δ565) deleting the C-terminal 14-3-3ζ binding sites retained 14-3-3ζ binding function, in contrast, deletion of the C-terminal residues 551 to 610 of GPIbα totally abolished 14-3-3ζ binding, indicating that the residues 551 to 564 of GPIbα are important in the interaction between 14-3-3ζ and GPIb-IX. An antibody recognizing phosphorylated R557GpSLP561 sequence reacted with GPIbα suggesting phosphorylation of a population of GPIbα molecules at Ser559, and a membrane permeable phosphopeptide (MP-P), R557GpSLP561 corresponding to residues 557 to 561 of GPIbα eliminated the association of 14-3-3ζ with Δ565. MP-P also promoted GPIb-IX association with the membrane skeleton, and inhibited ristocetin-induced platelet agglutination, VWF binding to platelets and platelet adhesion to immobilized VWF. Furthermore, a GPIb-IX mutant replacing Ser559 of GPIbα with alanine showed an enhanced association with the membrane skeleton, reduced ristocetin-induced VWF binding, and diminished ability to mediate cell adhesion to VWF under flow conditions. Conclusions: These data suggest a phosphorylation-dependent binding of 14-3-3ζ to central filamin A binding site of GPIbα, and the dimeric 14-3-3ζ binding to both the C-terminal site and central RGpSLP site inhibits GPIb-IX association with the membrane skeleton and promotes the VWF binding function of GPIb-IX.
Evolution of the Androgen Receptor Pathway during Progression of Prostate Cancer
Authors: Peter J.M. Hendriksen, Natasja F.J. Dits, Koichi Kokame, Antoine Veldhoven, Wytske M. van Weerden, Chris H. Bangma, Jan Trapman, Guido Jenster
Journal: Cancer Research (2006)

Abstract The present work focused on the potential involvement of selective adaptations of the androgen receptor pathway in the initiation and progression of prostate cancer. We defined the androgen receptor pathway by selecting 200 genes that were androgen responsive in prostate cancer cell lines and/or xenografts. This androgen receptor pathway gene signature was then used for profiling prostate cancer xenografts and patient-derived samples. Approximately half of the androgen receptor pathway genes were up-regulated in well-differentiated prostate cancer compared with normal prostate. Functionally distinct parts of the androgen receptor pathway were specifically down-regulated in high-grade cancers. Unexpectedly, metastases have down-regulated the vast majority of androgen receptor pathway genes. The significance of this progressive down-regulation of androgen receptor pathway genes was shown for a few androgen receptor–regulated genes. Lower mRNA expression of HERPUD1, STK39, DHCR24, and SOCS2 in primary prostate tumors was correlated with a higher incidence of metastases after radical prostatectomy. HERPUD1 mRNA expression predicted the occurrence of metastases almost perfectly. In vitro experiments showed that overexpression of the stress response gene HERPUD1 rapidly induces apoptosis. Based on the functions of the genes within the distinct subsets, we propose the following model. Enhanced androgen receptor activity is involved in the early stages of prostate cancer. In well-differentiated prostate cancer, the androgen receptor activates growth-promoting as well as growth-inhibiting and cell differentiation genes resulting in a low growth rate. The progression from low-grade to high-grade prostate carcinoma and metastases is mediated by a selective down-regulation of the androgen receptor target genes that inhibit proliferation, induce differentiation, or mediate apoptosis. (Cancer Res 2006; 66(10): 5012-20)
Time trends and demography of mortality after fractured neck of femur in an English population, 1968-98: database study
Authors: S. E Roberts
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To investigate time trends in mortality after admission to hospital for fractured neck of femur from 1968 to 1998, and to report on the effects of demographic factors on mortality. <b>Design</b> Analysis of hospital inpatient statistics for fractured neck of femur, incorporating linkage to death certificates. <b>Setting</b> Four counties in southern England. <b>Subjects</b> 32 590 people aged 65 years or over admitted to hospital with fractured neck of femur between 1968 and 1998. <b>Main outcome measures</b> Case fatality rates at 30, 90, and 365 days after admission, and standardised mortality ratios at monthly intervals up to one year after admission. <b>Results</b> Case fatality rates declined between the 1960s and the early 1980s, but there was no appreciable fall thereafter. They increased sharply with increasing age: for example, fatality rates at 30 days in 1984–98 increased from 4% in men aged 64–69 years to 31% in those aged ≥ 90. They were higher in men than women, and in social classes IV and V than in classes I and II. In the first month after fracture, standardised mortality ratios in women were 16 times higher, and those in men 12 times higher, than mortality in the same age group in the general population. <b>Conclusions</b> The high mortality rates, and the fact that they have not fallen over the past 20 years, reinforce the need for measures to prevent osteoporosis and falls and their consequences in elderly people. Whether post-fracture mortality has fallen to an irreducible minimum, or whether further decline is possible, is unclear.
FRI0397 Relationship between Igg Anti-Nr2 Glutamate Receptor Antibodies and Depressive/Anxiety Symptoms in Patients with Systemic Lupus Erythematosus
Authors: C.C. Mok, K.L. Chan, B. Diamond
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To study the relationship between anti-NR2 glutamate receptor antibodies (anti-NR2) and depressive/anxiety symptoms in patients with systemic lupus erythematosus (SLE). <h3>Methods</h3> Consecutive Chinese patients who fulfilled ≥4 ACR criteria for SLE were recruited. Depressive/anxiety symptoms were assessed by the validated Chinese version of the Hospital Anxiety and Depression scale (HADS) (0-21 points). Serum samples were taken at 10am in the morning for the assay of anti-NR2 antibodies (in-house ELISA using peptide adsorbed to plate and serum diluted 1:100, developed with an anti-human IgG antibody). Disease activity of patients recruited was assessed by SLEDAI and physicians9 global assessment (PGA), whereas organ damage since SLE diagnosis was assessed by the ACR/SLICC damage index (SDI). Correlation among anti-NR2 titer, age, sex, HADS-depression score, HADS-anxiety score, SLEDAI, PGA and SDI in various systems was studied by linear regression models. <h3>Results</h3> 285 SLE patients were studied (95% women; age 38.9±12.6 years; SLE duration 9.0±7.0 years). At the time of study, 57 (20%) patients had clinically active SLE (SLEDAI ≥5); and 106 (37%) patients had organ damage (SDI score ≥1). The mean SLEDAI was 3.9±4.6 and the mean PGA was 0.36±0.66. Forty-four (15%) patients had HADS-anxiety score of &gt;10 and 28 (9.8%) of patients had HADS-depression score of &gt;10. Anti-NR2 antibodies were present in 154 (54%) patients, defined as titers of greater than the mean+2SD (standard deviation) of healthy controls. Strongly positive values of anti-NR2 (defined as mean+4SD of controls) were found in 90 (32%) patients. Linear regression revealed that anti-NR2 reactivity correlated with SLEDAI score (Beta 0.25; p&lt;0.001), PGA score (Beta 0.31; p&lt;0.001), mean SLEDAI in the preceding 12 months (Beta 0.18; p=0.003), C3 level (Beta -0.25; p&lt;0.001), HADS-depression score (Beta 0.14; p=0.022) and HADS-anxiety score (Beta 0.14; p=0.023), adjusted for age and sex. There was no relationship between anti-NR2 titers and anti-dsDNA titer, total SDI damage score (Beta 0.09; p=0.14), neuropsychiatric damage (Beta 0.06; p=0.32) or SDI scores in other systems. <h3>Conclusions</h3> Anti-NR2 antibodies are prevalent in patients with SLE. Anti-NR2 reactivity correlated with disease activity and depressive/anxiety symptoms in SLE patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2633
Evidence based medicine: a movement in crisis?
Authors: T. Greenhalgh, J. Howick, N. Maskrey
Journal: BMJ (2014)

<b>Trisha Greenhalgh and colleagues</b> argue that, although evidence based medicine has had many benefits, it has also had some negative unintended consequences. They offer a preliminary agenda for the movement’s renaissance, refocusing on providing useable evidence that can be combined with context and professional expertise so that individual patients get optimal treatment
Microfluidic CD4 <sup>+</sup> and CD8 <sup>+</sup> T Lymphocyte Counters for Point-of-Care HIV Diagnostics Using Whole Blood
Authors: Nicholas N. Watkins, Umer Hassan, Gregory Damhorst, HengKan Ni, Awais Vaid, William Rodriguez, Rashid Bashir
Journal: Science Translational Medicine (2013)

A microfluidic biochip enumerates CD4 + or CD8 + T lymphocytes in whole blood of healthy and HIV-infected donors.
Clonal nature of the immune response. II. The effect of immunization on clonal commitment.
Authors: D E Briles, J M Davie
Journal: The Journal of Experimental Medicine (1980)

An inbred strain can produce several hundred different anti-group A carbohydrate (GAC) antibodies, as analyzed by isoelectric focusing. However, each individual mouse produces the bulk of its anti-GAC antibody as only one or two different spectrotypes, which appear to be randomly chosen. By using adoptive transfer techniques, we have observed that clonal commitment occurs very early in immunization, sometimes even before immunization, and thus does not result from competition among B cells for antigen. X
Survival for Patients With Single and Multiple Primary Melanomas
Authors: Anne Kricker
Journal: JAMA Dermatology (2013)

Objective-Little is known about survival after a diagnosis of a second or higher order (multiple) primary melanoma.We aimed to determine whether survival after diagnosis was better in patients with multiple primary melanomas (MPM) than with single primary melanomas (SPM), as suggested in a recent study.Design-Survival analysis with median follow-up of 7.6 years (range 0.4-10.6).Setting-The Genes, Environment and Melanoma (GEM) study enrolled incident cases of melanoma notified to population-based cancer registries in Australia, Canada, Italy and the USA.MPM were ascertained over a longer period than SPM.Participants-2372 patients with SPM and 1206 with MPM.Main outcome measures-Melanoma-specific fatality hazard ratios (HR) and confidence intervals (CI) associated with clinical and pathologic characteristics of SPM, MPM and both together in Cox regression models.Results-Thickness was the main determinant of fatality (HR for >4mm=7.68,95% CI 4.46 to 13.23); other independent predictors were ulceration, mitoses and scalp location.After adjustment for these other predictors, there was little difference in fatality between MPM and SPM (HR for MPM relative to SPM=1.24, 95% CI 0.91 to 1.69; P = .18).Thicker SPM, however, had higher fatality (HR for >4mm=13.56,95% CI 6.47-28.40)than thicker MPM (HR for >4mm=2.93,95% CI 1.17-7.30). Conclusion-Whileoverall fatalities from SPM and MPM were similar, relative fatality for thick SPM was greater than for thick MPM.This finding may offer support for a difference in outcome between patients with SPM and MPM that is worth further exploration.
PTX3 predicts severe disease in febrile patients at the emergency department
Authors: Martijn D. de Kruif, Maarten Limper, Karlien Sierhuis, Jiri F.P. Wagenaar, C. Arnold Spek, Cecilia Garlanda, Alessia Cotena, Alberto Mantovani, Hugo ten Cate, Pieter H. Reitsma, Eric C.M. van Gorp
Journal: Journal of Infection (2009)
Targeting the Tumor Microenvironment in Cancer: Why Hyaluronidase Deserves a Second Look
Authors: Clifford J. Whatcott, Haiyong Han, Richard G. Posner, Galen Hostetter, Daniel D. Von Hoff
Journal: Cancer Discovery (2011)

Increased extracellular matrix (ECM) deposition is a characteristic observed in many solid tumors. Increased levels of one ECM component-namely, hyaluronan (HA)-leads to reduced elasticity of tumor tissue and increased interstitial fluid pressure. Multiple initial reports showed that the addition of hyaluronidase (HYAL) to chemotherapeutic regimens could greatly improve efficacy. Unfortunately, the bovine HYAL used in those studies was limited therapeutically by immunologic responses to treatment. Newly developed recombinant human HYAL has recently been introduced into clinical trials. In this article, we describe the role of HA in cancer, methods of targeting HA, and clinical studies performed to date, and we propose that targeting HA could now be an effective treatment option for patients with many different types of solid tumors.
[597] EVOLUTION OF LIVER STIFFNESS MEASUREMENT DURING ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: C. Hezode, I. Rosa, L. Castera, D. Roulot, V. Leroy, M. Bouvier-Alias, F. Roudot-Thoraval, C. Douvin, A. Mallat, J.-M. Pawlotsky
Journal: Journal of Hepatology (2007)
Perifolliculitis capitis abscedens et suffodiens successfully controlled with infliximab
Authors: H.R.C. Brandt, A.P.R. Malheiros, M.G. Teixeira, M.C.R. Machado
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, Perifolliculitis capitis abscedens et suffodiens (dissecting cellulitis or dissecting folliculitis) manifests with perifollicular pustules, nodules, abscesses and sinus tracts on the scalp, eventually resulting in extensive scarring alopecia. When it is associated with acne conglobata and hidradenitis suppurativa the syndrome is referred to as the follicular occlusion triad, and when also with pilonidal cysts as a tetrad.1 The frequent association of these diseases suggests a common pathogenesis. Its course is chronic and relapsing, and treatment is frequently difficult. Therapies include isotretinoin, antibiotics, prednisone, X‐ray therapy, surgical excision and skin grafting.2 Tumour necrosis factor (TNF) is a proinflammatory cytokine that seems to play an important role in the pathogenesis of these diseases. Infliximab is a chimeric monoclonal antibody that binds specifically to TNF‐α, decreasing the effect of the cytokine in inflammatory diseases. Infliximab monotherapy has been shown to be an effective therapeutic alternative for severe extensive forms of hidradenitis suppurativa.3
Sex-Related Differences Between Adiponectin and Insulin Resistance in Schoolchildren
Authors: Pei-Ling Tsou, Yi-Der Jiang, Ching-Chung Chang, Jung-Nan Wei, Fung-Chang Sung, Chau-Ching Lin, Chuan-Chi Chiang, Tong-Yuan Tai, Lee-Ming Chuang
Journal: Diabetes Care (2004)

OBJECTIVE—To study the effect of body composition and adiponectin on insulin resistance and β-cell function in schoolchildren during puberty. RESEARCH DESIGN AND METHODS—Plasma adiponectin level and its relationships with insulin sensitivity and β-cell function were analyzed in 500 randomly recruited nondiabetic Taiwanese schoolchildren (245 boys and 255 girls) aged 6–18 years in a national survey program for diabetes in 1999. Insulin resistance and β-cell function were evaluated by homeostasis model assessment (HOMA). Plasma adiponectin concentrations were determined with radioimmunoassay. RESULTS—Plasma glucose levels remained stable, whereas insulin resistance increased with a compensatory rise in β-cell function during this period. A transient drop of adiponectin level with a trough at 10–12 years was found in boys but not in girls. This pubertal drop of adiponectin levels in boys coincides with the sharp rise in testosterone concentration. A negative correlation between testosterone levels and adiponectin concentration was also noted in boys (r = −0.142, P = 0.032). Plasma adiponectin levels correlated inversely with relative body weight, fasting insulin concentrations, and insulin resistance index by HOMA in boys aged 15–18 years and in girls aged 11–14 years. No association was observed between adiponectin levels and β-cell function by HOMA. CONCLUSIONS—There is a transient drop in the level of adiponectin during male puberty, correlated with the increase in testosterone level in boys. Plasma adiponectin levels were inversely correlated with obesity and insulin resistance in boys and girls during the pubertal period.