tbuckley/cabot-search huggingface dataset:
Reflex anal dilatation: effect of parting the buttocks on anal function in normal subjects and patients with anorectal and spinal disease.
Authors: N W Read, W M Sun
Journal: Gut (1991)

Anal dilatation in response to gentle parting of the buttocks has been advocated as a sign of sexual abuse in children, but nothing is known of the physiology of this response or its existence in normal subjects, in patients with spinal disease, and in patients with a weak sphincter and whether it can be elicited after training. To answer these questions we investigated the effect of parting the buttocks on anal function. Combined anal manometry and electromyography was conducted in six normal subjects (five men, one woman, aged 19-53 years), in 18 patients with faecal incontinence (three men, 15 women, aged 30-80 years), and in seven paraplegic patients (six men, one woman, aged 25-36 years), in four of whom the posterior sacral roots had been cut. Parting the buttocks in normal subjects reduced the pressure in the anal canal from 102 (20) to 14 (3) cm H2O (mean (SEM), p less than 0.00001), but did not cause the anus to gape. This drop in pressure was associated with increased electrical activity in the external anal sphincter. Normal subjects could consciously relax the external anal sphincter and reduce the anal pressure but not so as to result in anal gaping during traction on the buttocks, even after anal dilatation. Stimulation of the anal lining by moving a probe in and out of the anal canal increased the activity of the external anal sphincter, raising anal pressures. Paraplegic patients who had lost conscious control of their external sphincters showed anal gaping when the buttocks were parted. A similar phenomenon was seen in patients with faecal incontinence who had weakness of the external anal sphincter, while incontinent patients with weakness of both sphincters showed anal gaping even at rest. Inasmuch as the results of our study can be applied to children, the data suggest that reflex anal dilatation should only be used to support a diagnosis of sexual abuse if sphincter function is otherwise normal and there is no evidence of cerebrospinal disease. Although our results do not support the notion that children could become so conditioned to repeated digital or penile penetration of the anus that they can cause the anus to gape when the buttocks are parted, neither do they exclude it.
Association Between the Prevalence of Symptoms and Health-Related Quality of Life in Adult Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study
Authors: I-Chan Huang, Tara M. Brinkman, Kelly Kenzik, James G. Gurney, Kirsten K. Ness, Jennifer Lanctot, Elizabeth Shenkman, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull
Journal: Journal of Clinical Oncology (2013)

We investigated the association between prevalence of symptoms and health-related quality of life (HRQOL) in adult survivors of childhood cancer enrolled in the St Jude Lifetime Cohort study.
Autologous Stem-Cell Transplantation Can Be Performed Safely Without the Use of Blood-Product Support
Authors: Karen K. Ballen, Pamela S. Becker, Beow Yong Yeap, Barbara Matthews, David H. Henry, Patricia A. Ford
Journal: Journal of Clinical Oncology (2004)

Purpose Autologous stem-cell transplantation has been shown to be a curative procedure for a variety of leukemias and lymphomas. Most transplants require RBC and platelet support. We report the ability to perform autologous transplantation without blood-product support. Subjects and Methods In this study, we treated 26 patients with religious objection to blood products with autologous stem-cell support without the use of any blood products. Patients received a combination of granulocyte colony-stimulating factor (G-CSF), erythropoietin, and interleukin-11 or G-CSF alone to mobilize stem cells. Post-transplant patients received intravenous iron, erythropoietin, G-CSF, and epsilon aminocaproic acid. Results There were two major bleeding complications (8%), with two treatment-related deaths (8%). There were three minor bleeding complications (12%). The median fall in hemoglobin level was 4.7 g/dL; the median hemoglobin level 30 days after transplantation was 9.2 g/dL. The median total number of days with platelet count less than 10 × 10 9 /L was 4 days; the median days to platelet recovery greater than 20 × 10 9 /L was 12 days. Conclusion Autologous stem-cell transplantation can be performed safely without the use of any blood products.
Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma
Authors: Ann-Lii Cheng, Chao A. Hsiung, Ih-Jen Su, Pei-Jer Chen, Ming-Chih Chang, Chao-Jung Tsao, Woei-Yao Kao, Wu-Ching Uen, Chih-Hung Hsu, Hwei-Fan Tien, Tsu-Yi Chao, Li-Tzong Chen, Jacqueline Whang-Peng
Journal: Hepatology (2003)

Reactivation of hepatitis is one of the most serious complications of chemotherapy in lymphoma patients who are carriers of the hepatitis B virus (HBV). Glucocorticoids are linked to increased risk of HBV reactivation. This study seeks to clarify whether removal of glucocorticoids from chemotherapy regimens may decrease the risk of HBV reactivation. Eligible patients were seropositive for hepatitis B surface antigen (HBsAg) and had histologically proven non-Hodgkin's lymphomas for which intensive chemotherapy was indicated. Patients were randomized to receive either ACE (epirubicin, cyclophosphamide, and etoposide) or PACE (prednisolone + ACE). A total of 50 patients were enrolled, 25 each for the ACE and PACE arms. The cumulative incidence of HBV reactivation at 9 months after starting chemotherapy was 38% and 73% for ACE and PACE arm, respectively (P =.03). The degree of clinical hepatitis was significantly more severe in the PACE arm: 11 patients (44%) in the PACE and 3 patients (13%) in the ACE arm had ALT elevation more than 10-fold of normal (P =.025), and 7 patients (28%) in the PACE and 1 patient (4%) in the ACE arm had icteric hepatitis (P =.049). Complete remission of tumors occurred in 11 (46%) patients in the PACE and 8 (35%) patients in the ACE arm (P =.556). The estimated overall survival rate at 46 months was 68% in the PACE arm and 36% in the ACE arm, respectively (P =.18). In conclusion, steroid-free chemotherapy decreases the incidence and severity of HBV reactivation in HBsAg-positive lymphoma patients. However, further research is needed to evaluate whether steroid-free chemotherapy may confer a less satisfactory control of lymphoma.
Postmarketing Drug Surveillance
Authors: E. K. Borden
Journal: JAMA (1984)

<h3>To the Editor.—</h3> We concur with Rossi et al<sup>1</sup>that alert physicians and others spontaneously reporting their suspicions of adverse drug reactions is critical to the discovery of rare effects of marketed drugs. Spontaneous reporting is an essential element of the multicomponent postmarketing surveillance systems established by pharmaceutical manufacturers and the Food and Drug Administration. However, we disagree with the assumption that the reason for conducting systematic postmarketing drug surveillance is to identify unusual or unexpected adverse effects. The purpose of systematic surveillance is to quantify the occurrence of both beneficial and adverse effects, which is not possible with spontaneous reporting systems. Even expected effects that are occurring with reasonable frequency need to be quantified, particularly if they occur with a different frequency among previously unidentified subgroups of users. Furthermore, the failure of adversity to appear at a statistically significant level in the observation of 10,000 persons does not
Hibernating Myocardium Retains Metabolic and Contractile Reserve Despite Regional Reductions in Flow, Function, and Oxygen Consumption at Rest
Authors: James A. Fallavollita, Brian J. Malm, John M. Canty
Journal: Circulation Research (2003)

Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during stress. To test this hypothesis, pigs were chronically instrumented with a proximal left anterior descending artery stenosis for 3 months, resulting in severe anteroapical hypokinesis with reduced resting perfusion (0.78±0.05 versus 0.94±0.07 mL · min −1 · g −1 in remote, P &lt;0.01; and 0.99±0.08 in controls, P &lt;0.05). Open-chest studies confirmed resting dysfunction compared with normal controls (segment shortening 9.2±2.2% versus 23.5±1.1%, P &lt;0.05). Resting myocardial oxygen consumption was reduced (63±3 versus 77±6 μL · g −1 · min −1 in controls, P &lt;0.05), yet lactate consumption was normal. Although subendocardial perfusion failed to increase during graded, intravenous epinephrine infusion (n=8), peak segment shortening (to 17.3±3.1%, P &lt;0.05) and oxygen consumption (to 90±6 μL · g −1 · min −1 , P &lt;0.01) increased from the depressed resting levels. There was no lactate production in hibernating myocardium, and lactate uptake increased during stress (0.7±0.1 to 1.2±0.1 μmol · g −1 · min −1 , P &lt;0.05). The absence of metabolic evidence of ischemia was also confirmed during atrial pacing to a rate of 120 bpm (n=8). Thus, despite reductions in function and oxygen consumption at rest, hibernating myocardium retains the ability to increase metabolism without the development of acute ischemia. This supports the hypothesis that the downregulation of oxygen consumption and function in hibernating myocardium is an adaptive response that prevents a supply-demand imbalance during submaximal increases in cardiac workload when coronary flow reserve is limited.
A lower ratio of AT1/AT2 receptors of angiotensin II is found in female than in male spontaneously hypertensive rats
Authors: Michele Melo Silva-Antonialli, Rita C A Tostes, Lílian Fernandes, Débora Rejane Fior-Chadi, Eliana Hiromi Akamine, Maria Helena C Carvalho, Zuleica Bruno Fortes, Dorothy Nigro
Journal: Cardiovascular Research (2004)

Sexual dimorphism has been observed in arterial hypertension. Blood pressure levels are lower in female than in male spontaneously hypertensive rats (SHR). Angiotensin II (Ang II) plays a major role in the regulation of blood pressure. The aim of this study was to compare Ang II vascular reactivity and AT(1) and AT(2) receptor gene expression in female and male SHR.SHR animals were divided into four groups: (I) male, (II) female in physiological estrus, (III) ovariectomized and (IV) ovariectomized treated with estrogen. Arterial blood pressure, AT(1) and AT(2) mRNA expression were determined. Ang II responses in aorta and mesenteric vessels were also evaluated.In female SHR, aorta and mesenteric microvessels were hyporeactive to Ang II in comparison to male SHR. In ovariectomized females, Ang II vasoconstriction was similar to that of males. Estrogen treatment abolished this difference. The mRNA expression for AT(1) was higher in aorta and mesenteric vessels from males than in females. In ovariectomized SHR, mRNA expression for AT(1) was comparable to that of males. Treatment with estrogen reversed the over expression observed. Whereas AT(2) gene expression did not differ, a lower ratio AT(1)/AT(2) was found in female than in male vessels. A higher mRNA expression for AT(1) was observed in kidney from male than in female. Ovariectomy resulted in up-regulation of this subtype receptor. Treatment with estrogen reversed the overexpression. AT(2) gene expression was higher in kidney from female than male SHR. Ovariectomy reduced AT(2) gene expression and estrogen treatment reversed the alteration observed in kidney.There is sexual dimorphism in vascular reactivity and in receptor gene expression to Ang II in SHR. We conclude that estrogen modulates AT(1) and AT(2) receptor gene expression and that this might explain at least partially the lower blood pressure observed in female SHR.
Congenital Cardiovascular Anomalies Induced by Pteroylglutamic Acid Deficiency during Gestation in the Rat
Authors: CATHERINE D. C. BAIRD, MARJORIE M. NELSON, IAN W. MONIE, HERBERT M. EVANS
Journal: Circulation Research (1954)

Congenital cardiovascular anomalies were observed in the offspring when rats were placed on a dietary regimen deficient in pteroylglutamic ("folic") acid during gestation. These cardiovascular malformations occurred only when the mothers were given this diet for specific periods, as short as two or three days, in early pregnancy, at a time when the heart and aortic arches were in the initial stages of development.
Apoptotic Cells Initiate Endothelial Cell Sprouting via Electrostatic Signaling
Authors: Zhang Weihua, Rachel Tsan, Alan J. Schroit, Isaiah J. Fidler
Journal: Cancer Research (2005)

Abstract Angiogenesis, the development of new blood vessels from preexisting vessels, is crucial to tissue growth, repair, and maintenance. This process begins with the formation of endothelial cell sprouts followed by the proliferation and migration of neighboring endothelial cells along the preformed extensions. The initiating event and mechanism of sprouting is not known. We show that the phenotypic expression of negatively charged membrane surface in apoptotic cells initiates the formation of directional endothelial cell sprouts that extend toward the dying cells by a mechanism that involves endothelial cell membrane hyperpolarization and cytoskeleton reorganization but is independent of diffusible molecules. (Cancer Res 2005; 65(24): 11529-35)
S81 A randomised controlled study comparing the outcomes of pleural nurse practitioner versus doctors trained to perform pleural procedures for management of pleural effusions
Authors: ER Reid, PR Sivasothy, S Chatterji
Journal: Thorax (2013)

<h3>Background</h3> Following the National Patient Safety Agency alert in the UK thoracic ultrasound (TUS) is strongly recommended for all pleural procedures. This places strains on clinical service delivery. The role of the Nurse Practitioner (NP) in this setting is not established. We undertook a randomised control study to test the hypothesis that a Nurse Practitioner trained to Royal College of Radiologist level 1 TUS and in performing pleural procedures independently is equivalent to doctors trained in undertaking pleural procedures. <h3>Method</h3> In this prospective ethically approved un-blinded non-inferiority study we assessed pleural procedures as carried out by a Nurse Practitioner (Group A) in comparison with doctors trained in pleural procedures (Group B) in 32 patients. Primary endpoints were success of the pleural procedure, procedural pain using visual analogue score (VAS), patient anxiety using short form State Trait Anxiety Index (STAI). Secondary outcome measures were complications. Non parametric statistical tests were used for analysis. <h3>Results</h3> There was no statistically significant (NS) difference between groups as assessed by primary endpoints (Table 1). There was one failure to undertake therapeutic pleural aspiration in Group B. Delayed complications were drain dislodgement in Group A and re-expansion pulmonary oedema in Group B. <h3>Conclusion</h3> We believe this is the first randomised control study to test if after appropriate training a Pleural Nurse Practitioner is able to safely and effectively undertake pleural procedures with equivalence in practice to trained doctors.
Yes-Associated Protein 1 Exhibits Oncogenic Property in Gastric Cancer and Its Nuclear Accumulation Associates with Poor Prognosis
Authors: Wei Kang, Joanna H.M. Tong, Anthony W.H. Chan, Tin-Lap Lee, Raymond W.M. Lung, Patrick P.S. Leung, Ken K.Y. So, Kaichun Wu, Daiming Fan, Jun Yu, Joseph J.Y. Sung, Ka-Fai To
Journal: Clinical Cancer Research (2011)

Yes-associated protein 1 (YAP1) is a multifunctional protein that can interact with different transcription factors to activate gene expression. The role of YAP1 in tumorigenesis is unclear. We aimed to investigate the functional role of YAP1 in tumorigenesis of gastric cancer.YAP1 expression in gastric adenocarcinoma was evaluated. The biological function was determined by proliferation assay, colony formation, cell invasion, and flow cytometric analysis through knocking down or ectopic expressing YAP1 in gastric cancer cell lines coupled with in vivo study. The possible downstream effectors of YAP1 were investigated by expression microarray.YAP1 protein expression was upregulated in gastric cancer. Nuclear accumulation of YAP1 was associated with poor disease-specific survival (P = 0.021), especially in patients with early-stage diseases (P < 0.001). Knockdown YAP1 resulted in a significant reduction in proliferation, anchorage-dependent colony formation, cell invasion, and cell motility. Ectopic YAP1 expression promoted anchorage-independent colony formation, induced a more invasive phenotype, and accelerated cell growth both in vitro and in vivo. Microarray analysis highlighted the alteration of MAPK (mitogen-activated protein kinase) pathway by YAP1. We confirmed a constitutive activation of RAF/MEK/ERK (extracellular signal-regulated kinase) in YAP1-expressing MKN45 cells and further showed that YAP1 enhanced serum/epidermal growth factor-induced c-Fos expression in gastric cancer cells.Our findings supported that YAP1 exhibits oncogenic property in gastric cancer. We provided the first evidence that YAP1 exerted the oncogenic function by enhancing the capacity to activate the early-response gene pathway. YAP1 could be a prognostic biomarker and potential therapeutic target for gastric cancer.
T cell education dictates function
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2007)

How a young T cell is educated may dictate its future function, according to a new report by Li et al. (page 2145).

Young T cells receive survival signals through their T cell receptors during development. These signals are normally provided by epithelial cells in the thymus. But recent reports show that CD4+ thymocytes also signal to each other.

When stimulated by antigen, epithelium-educated CD4+ thymocytes can become helper T cells of all varieties—T helper (Th)-1, Th2, or Th17 cells—depending largely on the surrounding cytokines. But self-educated thymocytes, Li et al. now find, fail to make this lineage choice. These cells rapidly generated both interferon (IFN)-γ and interleukin (IL)-4, even when stimulated under conditions that normally inhibit IL-4 production. A ready-to-fire IL-4 locus and preformed IL-4 mRNA in the developing cells explained their tendency to continue synthesizing IL-4.

Mice whose thymocytes were forced to signal to each other to survive were less likely to develop allergic inflammation than were mice whose T cells developed normally. This protective effect might be due, the authors speculate, to the suppression of pro-allergic IL-4 by the IFNγ produced by these cells. Thus, people who have more self-educated T cells may be less allergy prone. But assessing the relative numbers of the two cell types in humans is difficult, as distinguishing surface markers have yet to be identified.

The team is now investigating how T cells decide between a thymocyte- and an epithelial cell–based education and how thymocyte-to-thymocyte signals set the cells up for an IL-4–producing future.
First-time prescriptions of biological disease-modifying antirheumatic drugs in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis 2002–2011: data from the NOR-DMARD register
Authors: Elisabeth Lie, Karen M Fagerli, Knut Mikkelsen, Erik Rødevand, Åse Lexberg, Synøve Kalstad, Till Uhlig, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2014)

Biological disease-modifying antirheumatic drugs (bDMARD) have constituted a major advance in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). In Norway, access to these therapies has been good since their introduction, with full reimbursement and no requirements of disease activity measures above certain cut-offs. With increasing focus on early and aggressive therapy, one could expect increasing prescription of bDMARDs, including use in patients with moderate disease activity. Our objectives were to examine if prescription rates of bDMARDs in RA, PsA and axSpA continue to increase or have reached a plateau, and whether disease activity at initiation of therapy has changed over the years.

Data for these analyses were provided by the NOR-DMARD register, which was established by three Norwegian rheumatology departments in 2000, with two more centres joining in 2002. The register has aimed for longitudinal follow-up of all patients with inflammatory joint diseases starting a new DMARD regimen.1 For the current analyses we included all prescriptions of bDMARDs in previously bDMARD-naive patients with …
Pregnancy in primary sclerosing cholangitis
Authors: B. E. Wellge, M. Sterneck, A. Teufel, C. Rust, A. Franke, S. Schreiber, T. Berg, R. Gunther, W. Kreisel, C. zu Eulenburg, F. Braun, U. Beuers, P. R. Galle, A. W. Lohse, C. Schramm
Journal: Gut (2011)

<h3>Background</h3> There is a paucity of data on fertility or pregnancy in patients with primary sclerosing cholangitis (PSC). <h3>Objective</h3> To assess fertility in PSC by comparing the number of children in a large cohort of PSC patients to healthy controls and to investigate the outcome of pregnancy, as well as the influence of pregnancy on the disease course. <h3>Design</h3> Case series. <h3>Setting</h3> Germany. <h3>Participants</h3> 229 PSC patients and 569 healthy controls were evaluated for the number of children. 17 patients with PSC and at least one pregnancy, or who received a diagnosis of PSC within 6 months after delivery, were included in the more detailed analysis. <h3>Main outcome measures</h3> Number of children per patient and control; disease activity during pregnancy and after delivery including maternal complications; long-term development of live births, fetal loss rate and the influence of medication on fetal and maternal outcome. <h3>Results</h3> Fertility did not seem to be reduced in PSC since the number of children did not differ between PSC patients and healthy controls. 25 pregnancies in 17 female PSC patients (median age at conception 31 years) were investigated in detail. An increase in liver enzymes was documented during five pregnancies (20%) and eight times (32%) post-partum. There were no serious maternal complications. All 21 live births presented with a normal perinatal and postnatal development over a median observation time of 50 months. Two pregnancies were delivered pre-term and four fetal losses occurred early in pregnancy (&lt;12 wk). Continuation of treatment with ursodeoxycholic acid (15/21) or azathioprine (2/21) had no negative effects on pregnancy outcome. <h3>Conclusions</h3> Fertility does not seem to be reduced in patients with PSC, who are able to deliver healthy children without an apparent increase in risk for mother or child.