tbuckley/cabot-search huggingface dataset:
Endothelin is an important determinant of renal function in a rat model of acute liver and renal failure
Authors: R Anand
Journal: Gut (2002)

Background and aims: Renal failure occurs in approximately 55% of patients with acute liver failure. We have previously shown that plasma endothelin 1 concentrations are elevated in patients with acute liver failure and the hepatorenal syndrome. There are few reported satisfactory animal models of liver failure together with functional renal failure. In this study, a rat model of acute liver failure induced by galactosamine that also develops renal failure was first characterised. This model was used to investigate the hypothesis that endothelin 1 is an important mediator involved in the pathogenesis of renal impairment that occurs in acute liver failure. Methods: Acute liver failure was induced in male Sprague-Dawley rats by intraperitoneal injection of galactosamine together with treatment with the endothelin receptor antagonist Bosentan. Twenty four hour urine collections were made using a metabolic cage. Renal blood flow was measured in anaesthetised animals. Results: This model developed renal failure and liver failure in the absence of any significant renal pathology, and with an accompanying fall in renal blood flow. Plasma concentrations of endothelin 1 were increased twofold following the onset of liver and renal failure (p&lt;0.05), and there was significant upregulation of the endothelin receptor A (ET<sub>A</sub>) in the renal cortex (p&lt;0.05). Administration of Bosentan prevented the development of renal failure when given before or 24 hours after the onset of liver injury (p&lt;0.05) but had no effect on liver injury itself, or on renal blood flow. Conclusions: This study demonstrates that this animal model has many of the features needed to be regarded as a model of renal failure that occurs in acute liver failure. The observation that plasma levels of endothelin 1 and ET<sub>A</sub> receptors are increased and upregulated, and that renal failure is prevented by an endothelin antagonist supports the hypothesis originally put forward that ET<sub>A</sub> is important in the pathogenesis of renal failure that occurs in patients with acute liver failure.
STUDIES OF THE FATE OF TYPE 1 POLIOVIRUSES IN FLIES
Authors: Margrét G. Gudnadóttir
Journal: The Journal of Experimental Medicine (1961)

Studies on the fate of type 1 polioviruses in two common species of flies were carried out. The amount of virus in carcasses and excreta at different times was determined by the plaque assay method. Flies and their excreta remained infective for 11 days when kept at room temperature or when incubated at 36 degrees C. for 2 hours a day. Flies remained infective for 3 months when kept in hibernation. A relative increase in titer was found to occur between 9 and 18 hours after feeding if the flies were incubated at 36 degrees C. for 5 to 15 hours a day. The peak occurred later, at 40 to 52 hours after feeding if less incubation was used. Titers in excreta were parallel to titers in carcasses. A twofold increase in titer over the initial feeding was observed on 3 occasions with type 1 Mahoney but not with the LSc strain of virus.
Can a rescuer or simulated patient accurately assess motion during cervical spine stabilisation practice sessions?
Authors: I Shrier, P Boissy, L Fecteau, J Mellete, R Steele, G O Matheson, D Garza, W H Meeuwisse, E Segal, J Boulay
Journal: British Journal of Sports Medicine (2011)

Background Proper stabilisation of suspected unstable spine injuries is necessary to prevent (worsen) spinal cord damage. Almost all training relies on subjective reports from the simulated patient or observations from an independent person. The reliability and validity of these measures remains unknown. Objective To determine 1) how accurately rescuers and simulated patients assess motion during cervical spine (c-spine) stabilisation practice, and 2) if providing feedback on performance influences behaviour preferences. Design Cross-over design. Setting and Participants 12 experienced therapists. Assessment Head Squeeze and Trap Squeeze (random order) c-spine stabilisation during four test scenarios: lift-and-slide (L&amp;S) and log-roll (LR) placement on spinal board, and agitated patient trying to sit up (AGIT-SIT) or rotate head (AGIT-ROT). Main outcome measurements Inter-rater reliability between rescuer and simulated patient quality scores for subjective evaluation of c-spine stabilisation during trials (0=best, 10=worst), correlation between rescuers' quality score and objective measure of motion with inertial measurement units (IMU), and frequency of change in preference for Head Squeeze vs Trap Squeeze. Results Although the weighted-kappa for inter-rater reliability was acceptable (0.71–0.74), scores varied by more than one points between rescuers/simulated patients for ∼10–15% of trials. Rescuers' scores correlated with objective measures but with large variability. For example, 38% of trials scored as almost perfect (0–1) by the rescuer actually had &gt;10° of motion in at least one direction. In general, feedback did not affect preference for L&amp;S. For the LR, 6/8 subjects preferring Head Squeeze at baseline preferred Trap Squeeze after feedback. For the confused patient, 5/5 subjects preferring Head Squeeze at baseline preferred Trap Squeeze after feedback. Conclusion Rescuers and simulated patients could not adequately assess performance during c-spine stabilisation without objective measures. Providing immediate feedback is a promising tool for teaching proper technique and for changing preferences of behaviour in this context.
Sonographically guided intratendinous injections of hyperosmolar dextrose/lidocaine: a pilot study for the treatment of chronic plantar fasciitis
Authors: M B Ryan, A D Wong, J H Gillies, J Wong, J E Taunton
Journal: British Journal of Sports Medicine (2008)

To report on the effectiveness of sonographically guided injections of hyperosmolar dextrose at reducing the pain associated with chronic plantar fasciitis.Case series.Ultrasound division of St Paul's Hospital.20 referrals (3 men, 17 women; age 51 (SD 13) years) from local sports medicine primary care practitioners who had failed previous conservative treatments.A 27-gauge needle administered a 25% dextrose/lidocaine solution under sonographic guidance at 6 week intervals returning for a median of three consultations.Visual analogue scale (VAS) items for pain levels at rest (VAS1), activities of daily living (VAS2), and during or after physical activity (VAS3) were recorded at baseline and at the final treatment consultation (post-test). A telephone interview conducted an average of 11.8 months after the post-test consultation provided a measure of long-term follow-up.16 patients reported a good to excellent outcome, while the symptoms in 4 patients were unchanged. There was a significant decrease (p<0.001) in all mean VAS items from pre-test to post-test: VAS1 (36.8 (SD 25.6) to 10.3 (10.9)), VAS2 (74.7 (20.8) to 25.0 (27.7)) and VAS3 (91.6 (9.2) to 38.7 (35.1)) and there were no apparent changes after the follow-up interview.Sonographically guided dextrose injections showed a good clinical response in patients with chronic plantar fasciitis insofar as pain was reduced during rest and activity. Further studies including a control group are needed to validate these outcomes.
Cisplatin plus doxorubicin plus cyclophosphamide in metastatic or recurrent thymoma: final results of an intergroup trial. The Eastern Cooperative Oncology Group, Southwest Oncology Group, and Southeastern Cancer Study Group.
Authors: P J Loehrer, K Kim, S C Aisner, R Livingston, L H Einhorn, D Johnson, R Blum
Journal: Journal of Clinical Oncology (1994)

PURPOSE The purpose of this study was to evaluate the impact of cisplatin, doxorubicin, and cyclophosphamide (PAC) in patients with advanced thymoma with respect to response rate, duration of remission, and overall survival. PATIENTS AND METHODS Assessable patients with thymoma (n = 29) or thymic carcinoma (n = 1) with metastatic or locally progressive recurrent disease following radiotherapy were treated with intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) with normal saline hydration. Courses were repeated every 3 weeks for a maximum of eight cycles of therapy. RESULTS Toxicity, which was primarily hematologic, was mild, with only one patient developing a fever associated with neutropenia. Three complete responses (CRs) and 12 partial responses (PRs) were observed (CR+PR rate, 50%; 95% confidence interval, 31.3% to 68.7%). Ten patients had stable disease. The median duration of response was 11.8 months (range, 0.9 to 70.5+), the time to treatment failure 18.4 months (range, 0.8 to 91.9+), and median survival time 37.7 months (range, 2 to 91.9+). CONCLUSION This trial demonstrates that objective response rates and prolonged survival can be achieved in patients with advanced thymoma.
Boosting innate immunity in cancer
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Boosting innate immunity in cancerMature DCs and the NKT cell ligand ␣ -galactosyl ceramide ( ␣ -GalCer) are a promising combination for boosting immunity in humans, according to a study on page 1503.Chang and colleagues used ␣ -GalCer-pulsed DCs to immunize cancer patients and showed that the treatment resulted in long-term expansion of both NKT cells and virus-specific CD8 ϩ T cells.␣ -GalCer, a glycolipid derived from marine sponges, was identified based on its antitumor properties.This foreign glycolipid was later found to be presented to NKT cells by DCs.NKT cells activated by this glycolipid can promote tumor regression in mice.Attempts to extend this work to humans, however, have met with limited success.␣ -GalCer treatment alone decreased NKT cell numbers in patients with solid tumors, and vaccination with ␣ -GalCer-pulsed immature DCs induced only modest and transient NKT cell expansion.Maturation of the DCs-treatment with cytokines that enhance the expression of MHC and costimulatory molecules-was the key to the approach used by Chang and colleagues.They immunized five advanced cancer patients, none of whom had detectable NKT cells in their blood before treatment.But with ␣ -GalCer-pulsed mature DCs, all patients had a rapid and sustained increase in NKT cell numbers.Surprisingly, CD8 ϩ T cells specific for cytomegalovirus were also expanded by ␣-GalCer-pulsed DCs activate NKT cells and antiviral T cells in advanced cancer patients.
Laminar Shear Stress Inhibits Vascular Endothelial Cell Proliferation by Inducing Cyclin-Dependent Kinase Inhibitor p21 <sup> <i>Sdi1/Cip1/Waf1</i> </sup>
Authors: Shigeo Akimoto, Masako Mitsumata, Toshiyuki Sasaguri, Yoji Yoshida
Journal: Circulation Research (2000)

Abstract —Alterations in the functions of vascular endothelial cells (ECs) induced by fluid shear stress may play a pivotal role in both the development and prevention of vascular diseases. We found that DNA synthesis of bovine aortic and human umbilical vein ECs, determined by [ 3 H]thymidine incorporation, was inhibited by steady laminar shear stress (5 and 30 dyne/cm 2 ). This growth inhibition due to shear stress was associated with suppression of cell transition from the G 1 to S phase of the cell cycle. Therefore, we studied G 1 -phase events to find the molecules responsible for this cell cycle arrest. Shear stress inhibited the phosphorylation of a retinoblastoma protein (pRb) and the activity of cyclin-dependent kinase (cdk) 2 and cdk4, which phosphorylate pRb. The level of cdk inhibitor p21 Sdi1/Cip1/Waf1 protein, but not that of p27 Kip1 , increased as a result of shear stress, and the amount of p21 protein associated with cdk2 also increased, although the protein level of cdk2 was unchanged. Shear stress markedly elevated the mRNA level of p21, and this elevation in mRNA faded after the release of cells from shear stress, concomitant with a recovery of DNA synthesis. These results suggest that steady laminar shear stress induces cell cycle arrest by upregulating p21. Derangement of the steady laminar flow may release cells from this inhibition and induce cell proliferation, which, in turn, may cause atherosclerosis through the induction of EC stability disruption.
Hypoglycemia: From the Laboratory to the Clinic
Authors: Stephanie A. Amiel
Journal: Diabetes Care (2009)

Hypoglycemia is the major, and most feared, complication of the pharmacological therapies for diabetes. In health, hypoglycemia sufficient to cause clinically relevant impairment of cognitive function or cardiac rhythm is prevented by highly efficient counterregulatory mechanisms that culminate in restoration of circulating glucose concentrations. In the accompanying article, McCrimmon (1) has summarized our current understanding of how these mechanisms may be initiated and coordinated by central glucose sensing, described the possible molecular mechanisms of neuronal glucose sensing, and alluded to the defective performance of these mechanisms in insulin-treated diabetes.

The principle clinical correlate of defective brain glucose sensing in diabetes is the change in the patient's awareness of the plasma glucose concentration. The clinical phenomenon of loss of awareness of hypoglycemia, and its associated increase in risk of severe hypoglycemia, is accompanied by measurable defects in the counterregulatory stress responses attributed at least in part to failure of central glucose sensing. As McCrimmon explains, the main determinant of the plasma glucose concentrations at which the brain responds actively to hypoglycemia appears to be the recent antecedent glucose exposure. Thus, people accustomed to chronic hyperglycemia may activate symptomatic stress responses as the glucose concentration falls within the physiological range—a barrier for some to tighten glucose control effectively. More extensively explored is the phenomenon of hypoglycemia unawareness, in which the body only mounts a protective counterregulatory response to falling blood glucose at glucose concentrations well below the physiologic norm. Added to the failure of glucagon responses to hypoglycemia that occurs early in type 1 diabetes, such additional counterregulatory failure may leave the patient symptom free and defenseless until plasma glucose concentrations are insufficient to support normal higher brain function. Confusion becomes the first sign of the hypoglycemia, and severe episodes (those in which the person is rendered incapable of self-treatment) ensue. In …
Effect of Late Night Calcium Supplements on Overnight Urinary Calcium Excretion in Premenopausal and Postmenopausal Women
Authors: P. E. Belchetz, M. H. Lloyd, R. G. S. Johns, R. D. Cohen
Journal: BMJ (1973)

The overnight urinary calcium/creatinine ratio is higher in the early years after the menopause than before it. However, the increment of urinary calcium/creatinine after a late evening calcium supplement is less in early postmenopausal than in premenopausal women. It is suggested that calcium therapy in postmenopausal osteoporosis may be best administered as a single late evening dose rather than in divided doses throughout the day.
Dronedarone for Atrial Fibrillation
Authors: Primiano Iannone, Enrico Haupt, Gaddo Flego, Paola Truglio, Monica Minardi, Simon Clarke, Nicola Magrini
Journal: JAMA Internal Medicine (2014)

Concerns have been expressed about the reliability of clinical practice guidelines. We analyzed 3 guidelines from medical specialty societies about dronedarone hydrochloride, an antiarrhythmic drug related to amiodarone hydrochloride, for treatment of patients with atrial fibrillation. We compared the recommendations in these guidelines with the conclusions about dronedarone that we reached by applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Method to the same evidence base. In our analysis, as a rate control drug, dronedarone was better than placebo only for a surrogate outcome (heart rate). As a rhythm control drug, dronedarone was associated with 13 (95% CI, -15 to 61) excess deaths per 1000 patients treated as compared with placebo. Compared with amiodarone, dronedarone was less effective (214 [95% CI, 130 to 294] more recurrences of atrial fibrillation per 1000 patients treated) and similarly tolerated (-28 [95% CI, -69 to 33] more serious adverse events requiring drug suspension per 1000 patients treated). Despite the limits of the evidence, all 3 guidelines recommended dronedarone for prevention of recurrences of atrial fibrillation; 2 of the guidelines recommended it as a rate control agent. Our findings raise questions about the reliability of these clinical practice guidelines, as well as the financial associations between many of the panel members and the manufacturer of dronedarone.
The Role of Surgery in N2 Non–Small Cell Lung Cancer
Authors: Malcolm M. DeCamp, Simon Ashiku, Robert Thurer
Journal: Clinical Cancer Research (2005)

Abstract Historical series document the poor survival (7-16% at 5 years) for patients with N2-positive, stage IIIA non–small cell lung cancer (NSCLC) treated with primary surgery. In 1994, two small randomized trials showed the superiority of induction chemotherapy followed by surgery over surgery alone for stage IIIA NSCLC. These findings, as well as subsequent studies showing the superiority of chemoradiotherapy over chemotherapy alone in nonoperable stage III disease, prompted investigations of preoperative chemoradiotherapy for N2-positve patients. As induction therapy improved, the use of resection in stage IIIA NSCLC was called into question. An Intergroup trial addressing this issue randomized 392 patients to induction chemoradiotherapy followed by surgery versus definitive chemoradiotherapy. Surgery following induction chemoradiotherapy was associated with a significant improvement in progression-free survival and almost a 50% reduction in local failure. As distant relapse is common, survival is likely to be enhanced only in those patients who respond to the systemic arm of treatment. Identification of genetic or biochemical markers of response, minimally invasive techniques to pathologically restage, or improved statistical or chemosensitivity analyses are needed to enhance our ability to select patients who will benefit from resection.
Localization of Pacemaker Channels in Lipid Rafts Regulates Channel Kinetics
Authors: Andrea Barbuti, Biagio Gravante, Monica Riolfo, Raffaella Milanesi, Benedetta Terragni, Dario DiFrancesco
Journal: Circulation Research (2004)

Lipid rafts are discrete membrane subdomains rich in sphingolipids and cholesterol. In ventricular myocytes a function of caveolae, a type of lipid rafts, is to concentrate in close proximity several proteins of the β-adrenergic transduction pathway. We have investigated the subcellular localization of HCN4 channels expressed in HEK cells and studied the effects of such localization on the properties of pacemaker channels in HEK and rabbit sinoatrial (SAN) cells. We used a discontinuous sucrose gradient and Western blot analysis to detect HCN4 proteins in HEK and in SAN cells, and found that HCN4 proteins localize to low-density membrane fractions together with flotillin (HEK) or caveolin-3 (SAN), structural proteins of caveolae. Lipid raft disruption by cell incubation with methyl-β-cyclodextrin (MβCD) impaired specific HCN4 localization. It also shifted the midpoint of activation of the HCN4 current in HEK cells and of I f in SAN cells to the positive direction by 11.9 and 10.4 mV, respectively. These latter effects were not due to elevation of basal cyclic nucleotide levels because the cholesterol-depletion treatment did not alter the current response to cyclic nucleotides. In accordance with an increased I f , MβCD-treated SAN cells showed large increases of diastolic depolarization slope (87%) and rate (58%). We also found that the kinetics of HCN4- and native f-channel deactivation were slower after lipid raft disorganization. In conclusion, our work indicates that pacemaker channels localize to lipid rafts and that disruption of lipid rafts causes channels to redistribute within the membrane and modifies their kinetic properties.
Clinical study of liver blood flow in man measured by 133Xe clearance after portal vein injection.
Authors: S B Sherriff, R C Smart, I Taylor
Journal: Gut (1977)

During the course of a clinical trial to assess the value of adjuvant liver perfusion of 5-fluorouracil after surgery for colorectal cancer, liver blood flow was measured in 14 patients. Access to the portal circulation was achieved by dilatation and cannulation of the obliterated umbilical vein. The clearance from the liver of a bolus of 133Xe was monitored using a gamma-ray camera so that blood flow from different areas of the liver could be calculated. The clearance curve of 133Xe was a double exponential of which the initial fast component accounted for a consistently high proportion of the total clearance. The perfusion studies have shown wide differences in blood flow to the various areas of the liver in the same patient, in addition to a wide variation in perfusion rate between the 14 patients. This technique of quantitative estimations of liver blood flow to different areas of the liver may have importance in planning operative procedures and understanding the haemodynamic mechanisms involved in liver disease.
Diagnosis and management of dysmenorrhoea
Authors: Michelle Proctor, Cynthia Farquhar
Journal: BMJ (2006)

The prevalence of dysmenorrhoea (painful menstrual cramps of uterine origin) is difficult to determine because of different definitions of the condition—prevalence estimates vary from 45% to 95%. However, dysmenorrhoea seems to be the most common gynaecological condition in women regardless of age and nationality.1 2 Absenteeism from work and school as a result of dysmenorrhoea is common (13% to 51% women have been absent at least once and 5% to 14% are often absent owing to the severity of symptoms).3 Dysmenorrhoea, especially when it is severe, is associated with a restriction of activity and absence from school or work. Yet despite this substantial effect on their quality of life and general wellbeing, few women with dysmenorrhoea seek treatment as they believe it would not help.w1

We used Medline (1966 to March 2006) to conduct a literature search of the Cochrane Database of Systematic Reviews on the Cochrane Library, issue 1, 2006, and we searched citation lists of relevant publications, including studies for randomised controlled trials (RCTs) and review articles. We used the following subject headings and keywords: dysmenorrhoea, dysmenorrhea, menstrual pain, period pain, and pelvic pain.

Dysmenorrhoea is commonly divided into two categories based on pathophysiology (table). Primary dysmenorrhoea is menstrual pain without organic disease, and secondary dysmenorrhoea is menstrual pain associated with an identifiable disease. Common causes of secondary dysmenorrhoea include endometriosis, fibroids (myomas), adenomyosis, endometrial polyps, pelvic inflammatory disease, and the use of an intrauterine contraceptive device.

View this table:

Differential diagnosis of primary and secondary dysmenorrhoea



Until recently, many medical and gynaecological texts ascribed the source of dysmenorrhoea to emotional or psychological problems—for example, anxiety, emotional instability, a faulty outlook on sex and menstruation, and imitation of the mother's feelings about menstruation.w2 However, experimental and clinical research has identified a physiological reason for dysmenorrhoea—the production of …
Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001
Authors: N Mauritzson, M Albin, L Rylander, R Billström, T Ahlgren, Z Mikoczy, J Björk, U Strömberg, PG Nilsson, F Mitelman, L Hagmar, B Johansson
Journal: Leukemia (2002)