tbuckley/cabot-search huggingface dataset:
Reticulon 4B (Nogo-B) facilitates hepatocyte proliferation and liver regeneration in mice
Authors: Lili Gao, Teruo Utsumi, Keitaro Tashiro, Bo Liu, Dahai Zhang, Scott E. Swenson, Yasuko Iwakiri
Journal: Hepatology (2013)

Nogo-B, also known as reticulon 4B, promotes liver fibrosis and cirrhosis by facilitating the transforming growth factor β (TGF-β) signaling pathway in activated hepatic stellate cells. The aim of this study was to determine the role of Nogo-B in hepatocyte proliferation and liver regeneration. Partial hepatectomy (PHx, 70% resection) was performed in male wild-type (WT) and Nogo-A/B knockout mice (referred to as Nogo-B KO mice). Remnant livers were isolated 2 hours, 5 hours, and 1, 2, 3, 7, and 14 days after PHx. Hepatocyte proliferation was assessed by Ki67 labeling index. Quantitative real-time polymerase chain reaction was performed for genes known to be involved in liver regeneration. Hepatocytes isolated from WT and Nogo-B KO mice were used to examine the role of Nogo-B in interleukin-6 (IL-6), hepatocyte growth factor (HGF), epidermal growth factor (EGF), and TGF-β signaling. Nogo-B protein levels increased in the regenerating livers in a time-dependent manner after PHx. Specifically, Nogo-B expression in hepatocytes gradually spread from the periportal toward the central areas by 7 days after PHx, but receded notably by 14 days. Nogo-B facilitated IL-6/signal transducer and activator of transcription 3 signaling, increased HGF-induced but not EGF-induced hepatocyte proliferation, and tended to reduce TGF-β1–induced suppression of hepatocyte proliferation in cultured hepatocytes. Lack of Nogo-B significantly induced TGF-β1 and inhibitor of DNA binding expression 1 day after PHx and IL-6 and EGF expression 2 days after PHx. Lack of Nogo-B delayed hepatocyte proliferation but did not affect the liver-to-body ratio in the regenerative process. Conclusion: Nogo-B expression in hepatocytes facilitates hepatocyte proliferation and liver regeneration.
From whom do children catch pertussis?
Authors: M G Thomas, H P Lambert
Journal: BMJ (1987)

Enquete sur 26 familles (90 personnes au total) dans lesquelles 1 enfant au moins a ete atteint de coqueluche. La contamination se fait frequemment par un des parents atteint soit de coqueluche typique, soit de coqueluche atypique, soit d'infection asymptomatique par Bordetella pertussis
Women's Mental Health in Africa
Authors: Leslie Hartley Gise
Journal: JAMA (1992)

The topics in the important book Wo<i>men's Mental Health in Africa</i>range from spirit possession to the acquired immunodeficiency syndrome (AIDS), and the contributors are from countries representing both East Africa and West Africa. The book is short, informative, interesting, and readable, so if any of the following questions interests you, you should read it. How have psychiatric problems of women in Nigeria become associated with increased education? How is it that both traditional cultural values and modernization have become stressful for African women today? How is the ancient cult of Zar similar to conventional, Western mental health treatment? How do the ceremonies of Zar work among Sudanese women in treating mental health problems, such as pain or depression? Why are Zar ceremonies becoming more popular among the literate, urban, middle and upper classes? What is the background and training of the sheikha, priestess, or leader in the Zar
NHS managers add voice to calls for changes to health bill
Authors: A. Gulland
Journal: BMJ (2011)

NHS managers have called for a major overhaul of plans to reform the NHS in their response to the government’s listening exercise.

The NHS Confederation, which represents health service managers, said in its submission to the NHS Future Forum, which is conducting the listening exercise, that reform of the NHS was needed. It added, however, that the government had not made the case for such major change and that reforms were not sufficiently focused on the difficulties facing the NHS such as the financial squeeze, variability in standards of care, …
Results of a Placebo-Controlled Study of the Metabolic Effects of the Addition of Metformin to Sulfonylurea-Treated Patients: Evidence for a central role of adipose tissue
Authors: Fahim Abbasi, Vinaya Kamath, Ali A Rizvi, Marcello Carantoni, Y D I Chen, Gerald M Reaven
Journal: Diabetes Care (1997)

OBJECTIVE To define the metabolic effects of metformin in the treatment of NIDDM and to evaluate potential mechanisms for its ability to improve glycemic control. RESEARCH DESIGN AND METHODS Sulfonylurea-treated patients, with inadequate glycemic control, were treated with metformin in either a placebo-controlled or open fashion. Measurements were made of 1) fasting and postprandial plasma glucose, insulin, and free fatty acid (FFA) concentrations; 2) glucose appearance and disappearance rates measured overnight with 3-[3H]glucose; and 3) plasma FFA concentrations during a 45-min infusion period at relatively low (∼ 60 pmol/l) insulin concentrations. RESULTS Mean ± SE hourly plasma glucose, insulin, and FFA concentrations were similar before and after treatment in the placebo group. In contrast, mean hourly plasma glucose concentrations were significantly lower (P &amp;lt; 0.005) after metformin treatment in both the placebo-controlled and open-label groups (−3.9 ± 1.0 and −4.4 ± 0.8 mmol/l, respectively). Similarly, day-long hourly FFA levels were lower (P &amp;lt; 0.005) following metformin in the placebo-controlled and open-label groups (−87 ± 35 and −136 ± 31 μmol/l, respectively). Plasma insulin concentrations did not change with treatment in any group. Overnight glucose turnover studies indicated that neither the rate of glucose appearance (hepatic glucose production) or glucose disappearance changed significantly with treatment in the placebo or metformin groups. Because plasma glucose concentration was much lower after metformin treatment, overnight glucose metabolic clearance rate was significantly (P &amp;lt; 0.001) lower in this group. Finally, plasma FFA concentrations in response to a low-dosage insulin infusion (5 mU · m−2 · min−1) were significantly lower after metformin as compared with the placebo-treated group (P &amp;lt; 0.001). CONCLUSIONS Metformin treatment was associated with significantly lower day-long plasma glucose and FFA concentrations. Although overnight hepatic glucose production was unchanged following treatment with metformin, the overnight glucose metabolic clearance rate significantly increased. Given these findings, it is suggested that at least part of the antihyperglycemic effect of metformin is due to an increase in glucose uptake, secondary to a decrease in release of FFA from adipose tissue, and lower circulating FFA concentrations.
The Articular Manifestations of Chronic Ulcerative Colitis
Authors: Luis Fernandez-Herlihy
Journal: New England Journal of Medicine (1959)

IT appears to be a well established belief that arthritis is an occasional complication of chronic ulcerative colitis, that its presence is an additional indication for surgical management of the colitis, and that removal of the diseased colon results in remission of the arthritic symptoms. The literature is vague, however, regarding the type of arthritis involved and its rate of occurrence.It is the purpose of this paper to attempt a classification of the articular manifestations of chronic ulcerative colitis, to estimate their frequency in a large group of patients and to correlate them to the activity of the colitis. . . .
The significance of the bone marrow biopsy pattern in chronic lymphocytic leukemia: A prognostic dilemma
Authors: Nurullah Zengin, Ay?e Kars, Arzu Sungur, Neslihan ?nci Zengin, Mutlu Hayran, G�lten Tekuzman, Emin Kansu, ?evket Ruacan, Din�er F?rat
Journal: American Journal of Hematology (1999)

Although bone marrow biopsy pattern (BMBP) has long been suggested to be an independent prognostic factor in chronic lymphocytic leukemia (CLL), conflicting reports continue to appear in the literature. To investigate this issue we retrospectively reviewed 70 CLL patients who had undergone bone marrow biopsy at the time of diagnosis in a multivariate Cox regression analysis together with other prognostic factors. There were 51 (72.8%) males and 19 (27.2%) females with a median age of 60 years (range, 38-77). The median follow-up time was 24 months (range, 1-76), and median survival was 44 months. Thirtyfour patients (48.6%) had diffuse and 36 patients (51.4%) had nondiffuse BMBP (14 nodular, 11 interstitial, and 11 mixed). The median survival for diffuse and nondiffuse BMBP groups were 17 and 53 months, respectively (P= 0.05). Sixteen patients (22. 9%) had stage A, 28 (40.0%) stage B, and 26 (37.1%) stage C disease according to the Binet system, and four patients (5.7%) had low-risk, 39 (55.7%) intermediate-risk, and 27 (38.6%) high-risk disease according to the modified Rai staging system. The difference between the median survivals of patients in different stages was statistically significant (P < 0.0001). The BMBP and staging systems that are thought to be significant predictors of prognosis were used to build a multivariate Cox proportional hazard model. BMBP was not found to add additional information to the prognostic value of the staging systems. Our results underline two points: first, the significance of BMBP must be investigated in multivariate analysis including the stage, and second, BMBP is not a dynamic prognostic parameter, it is an index of tumor burden and does not add any prognostic information beyond that provided by clinical stage.
Hedgehog pathway activation parallels histologic severity of injury and fibrosis in human nonalcoholic fatty liver disease
Authors: Cynthia D. Guy, Ayako Suzuki, Marzena Zdanowicz, Manal F. Abdelmalek, James Burchette, Aynur Unalp, Anna Mae Diehl
Journal: Hepatology (2011)

The Hedgehog (HH)-signaling pathway mediates several processes that are deregulated in patients with metabolic syndrome (e.g., fat mass regulation, vascular/endothelial remodeling, liver injury and repair, and carcinogenesis). The severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome generally correlate. Therefore, we hypothesized that the level of HH-pathway activation would increase in parallel with the severity of liver damage in NAFLD. To assess potential correlations between known histologic and clinical predictors of advanced liver disease and HH-pathway activation, immunohistochemistry was performed on liver biopsies from a large, well-characterized cohort of NAFLD patients (n = 90) enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Database 1 study. Increased HH activity (evidenced by accumulation of HH-ligand–producing cells and HH-responsive target cells) strongly correlated with portal inflammation, ballooning, and fibrosis stage (each P &lt; 0.0001), supporting a relationship between HH-pathway activation and liver damage. Pathway activity also correlated significantly with markers of liver repair, including numbers of hepatic progenitors and myofibroblastic cells (both P &lt; 0.03). In addition, various clinical parameters that have been linked to histologically advanced NAFLD, including increased patient age ( P &lt; 0.005), body mass index ( P &lt; 0.002), waist circumference ( P &lt; 0.0007), homeostatic model assessment of insulin resistance ( P &lt; 0.0001), and hypertension ( P &lt; 0.02), correlated with hepatic HH activity. Conclusion: In NAFLD patients, the level of hepatic HH-pathway activity is highly correlated with the severity of liver damage and with metabolic syndrome parameters that are known to be predictive of advanced liver disease. Hence, deregulation of the HH-signaling network may contribute to the pathogenesis and sequelae of liver damage that develops with metabolic syndrome.
Thrombolytic Therapy and Fatal Pulmonary Emboli
Authors: J. HIRSH
Journal: Annals of Internal Medicine (1971)

Letters and Comments1 July 1971Thrombolytic Therapy and Fatal Pulmonary EmboliJ. HIRSH, M.D., F.R.A.C.P.J. HIRSH, M.D., F.R.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-1-140 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: May I comment on the letter to the Editor by Dr. Jerzy Gajewski, in the March issue of the ANNALS, on "Thrombolytic Therapy and Fatal Massive Pulmonary Emboli." The possibility that treatment of venous thrombosis with thrombolytic agents may induce pulmonary embolism is often raised, but, as Dr. Gajewski points out, the reported incidence of this association is low (1). We have previously noted evidence of rethrombosis in patients with deep-vein thrombosis treated with streptokinase. This tends to occur when the plasminogen falls to low levels, at which time the thrombin time begins to return to normal...References1. SCHMUTZLERKOLLER RF: Thrombolytic therapy, in Recent Advances in Blood Coagulation. London, J. & A. Churchill Ltd., 1969, p. 299 Google Scholar2. HIRSHMCDONALDHALE JIG: Comparison of the effects of streptokinase and heparin on the early rate of resolution of major pulmonary embolism. Canad Med Assoc J 104:488, 1971 MedlineGoogle Scholar3. JOHNSONMCCARTHY AW: The lysis of artificially induced intravascular clots in man by intravenous infusions of streptokinase. J Clin Invest 38:1627, 1959 CrossrefMedlineGoogle Scholar1. NIEWIAROWSKIGUREWICH SV: Platelets in the fibrinolytic state, in Proceedings of the 9th Annual Symposium on Blood, Detroit, 1971, p. 8 Google Scholar2. HUMEGUREWICHDEALY MVJ: Streptokinase for chronic arterial disease: effective lysis and thromboembolic complications. Thromb Diath Haemorrh. In press Google Scholar3. GAJEWSKI J: Thrombolytic therapy and fatal massive pulmonary emboli. Ann Intern Med 74:450, 1971 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAnticoagulants 1 July 1971Volume 75, Issue 1Page: 140-141KeywordsFallsPulmonary embolismThrombinThrombosis ePublished: 1 December 2008 Issue Published: 1 July 1971 PDF downloadLoading ...
The New Era of Cardioversion
Authors: Sidney Alexander
Journal: JAMA (1986)

WITH the publication of this important article, describing the first clinical application of synchronized capacitor direct current (DC) discharge, the era of elective electrical treatment of cardiac arrhythmias began. The development of this method, so commonly used we tend to take it for granted, is a paradigm of the brilliant wedding of clinical acumen and profound understanding of good basic science, when chance did indeed favor the prepared mind. Its history is worth reviewing. <h3>A Signal Patient</h3> On Dec 1, 1960, a 59-year-old man was admitted to Bernard Lown's service at the Peter Bent Brigham Hospital in Boston with chief complaints of sweating, palpitations, and shortness of breath. Eleven years before, he had sustained an acute myocardial infarction. Several years later, episodes of atrial and ventricular rhythm disturbances began. The night before this admission, he had developed severe palpitations. Treatment elsewhere over the next 24 hours with 3.5 g of
Faecal peritonitis induced by picolax.
Authors: R F Phipps, S Fraser
Journal: BMJ (1987)

relaxation phases.He was given plentiful fluids and nutritious food and sedated with haloperidol 5 mg eight hourly.Within 48 hours his mental state was much improved and regular sedation was stopped.In view of the hypertensive heart disease thyroxine replacement was started cautiously-25 ,g on alternate days, increasing weekly by 25 mg on alternate days to 50 mg daily.Transaminase activities became normal within a week, but renal impairment persisted (see table ).The patient spent one month in hospital, during which his mental state settled gradually and was normal by the time of discharge without psychoactive drugs.
Electron-Beam Computed Tomography, Coronary Artery Calcium, and Evaluation of Patients with Coronary Artery Disease
Authors: Anthony S. Fiorino
Journal: Annals of Internal Medicine (1998)

Purpose: To briefly review the role of calcium in the pathophysiology of atherosclerosis and to comprehensively review and analyze studies of coronary artery calcium detected by electron-beam computed tomography (CT). Data Sources: The English-language literature located through MEDLINE and Current Contents. Study Selection: All studies of electron-beam CT in symptomatic and asymptomatic patients with and without known coronary artery disease were selected. Data Extraction: Significant findings on the association of cardiac risk factors and angiographically evident coronary artery disease with coronary artery calcium detected on electron-beam CT were compared. Prospective data on clinical outcomes in patients with coronary artery calcium were assessed. Data Synthesis: Coronary artery calcium is common in patients with known coronary artery disease or risk factors for coronary artery disease, and it becomes more common with increasing age. Coronary artery calcium detected by electron-beam CT is a sensitive but not a specific indicator of angiographically evident atherosclerosis; sensitivity is increased and specificity is decreased for angiographically significant disease. Test characteristics can be adjusted to improve specificity at the cost of sensitivity. Very limited data suggest that patients with coronary artery calcium are more likely to have cardiac events. Conclusions: Electron-beam CT is a promising new tool for the evaluation of coronary artery disease because patients who have coronary artery calcium are likely to have angiographically evident atherosclerosis. However, too few data currently exist to support the broad use of this tool in clinical decision making during the evaluation of patients with known or suspected coronary artery disease.
US journal embroiled in another conflict of interest scandal
Authors: D. Josefson
Journal: BMJ (1998)

The New England Journal of Medicine is facing criticism for publishing a scathing review of a book which claimed that industrial and environmental pollutants may be responsible for outbreaks of cancer.

The review was written by Dr Jerry Berke, the medical director of W R Grace, a chemical company currently being blamed for polluting drinking water in a Boston suburb and for contaminating soils in Maryland with thorium.

The review of the book ( Living Downstream: An Ecologist Looks at Cancer and the Environment by Sandra Steingraber) appears in the issue of 20 November (1997;337:1562). In his review Dr Berke calls the book …
Effectiveness of long term oral anticoagulation treatment in preventing venous thrombosis in hereditary protein S deficiency.
Authors: J J Michiels, J Stibbe, R Bertina, A Broekmans
Journal: BMJ (1987)

In eight of 14 patients who were deficient in protein S and who belonged to two unrelated families thrombosis presented as thrombophlebitis in seven and deep vein thrombosis in six, complicated by pulmonary embolism in four and leg ulcers in two. In four patients superficial thrombophlebitis preceded deep vein thrombosis by one to 11 years. Post-thrombotic varicose veins and venous insufficiency had developed in four patients. In three of those and in a fourth patient symptomatic superficial thrombophlebitis, deep vein thrombosis, and pulmonary embolism did not recur while they were taking oral anticoagulant treatment for six to 12 years. The anticoagulation intensity corresponded to international normalised ratio values of over 2.5. It is concluded that the benefits of anticoagulant treatment for patients with congenital thrombotic disease are great, and thus it is necessary to make an early diagnosis and treat patients at risk of developing thrombosis.
Patient-Reported Outcomes Assessment in Cancer Trials: Taking Stock, Moving Forward
Authors: Joseph Lipscomb, Bryce B. Reeve, Steven B. Clauser, Jeffrey S. Abrams, Deborah Watkins Bruner, Laurie B. Burke, Andrea M. Denicoff, Patricia A. Ganz, Kathleen Gondek, Lori M. Minasian, Ann M. O'Mara, Dennis A. Revicki, Edwin P. Rock, Julia H. Rowland, Maria Sgambati, Edward L. Trimble
Journal: Journal of Clinical Oncology (2007)

To evaluate and improve the use of cancer trial end points that reflect the patient's own perspective, the National Cancer Institute organized an international conference, Patient-Reported Outcomes Assessment in Cancer Trials (PROACT), in 2006. The 13 preceding articles in this special issue of the Journal were commissioned in preparation for or in response to the PROACT conference, which was cosponsored by the American Cancer Society. Drawing from these articles and also commentary from the conference itself, this concluding report takes stock of what has been learned to date about the successes and challenges in patient-reported outcome (PRO) assessment in phase III, phase II, and symptom management trials in cancer and identifies ways to improve the scientific soundness, feasibility, and policy relevance of PROs in trials. Building on this synthesis of lessons learned, this article discusses specific administrative policies and management procedures to improve PRO data collection, analysis, and dissemination of findings; opportunities afforded by recent methodologic and technologic advances in PRO data collection and analysis to enhance the scientific soundness and cost efficiency of PRO use in trials; and the importance of better understanding the usefulness of PRO data to the full spectrum of cancer decision makers, including patients and families, health providers, public and private payers, regulatory agencies, and standards-setting organizations.
Neutrophil Cytoskeletal Rearrangements during Capillary Sequestration in Bacterial Pneumonia in Rats
Authors: Kazuo Yoshida, Ryoichi Kondo, Qin Wang, Claire M. Doerschuk
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Neutrophils accumulate in pulmonary capillaries during acute inflammation. Initial events in injury recognition and sequestration do not occur through selectin-mediated rolling. Cytoskeletal rearrangements, as assessed by submembrane F-actin rims, result in poorly deformable neutrophils that may not pass through capillaries.Objective: To test the hypothesis that neutrophils sequestering during pneumonia contain F-actin rims and to determine the roles of CD11/CD18, L-selectin expression, and neutrophil-platelet adhesion in neutrophil sequestration.Methods: Neutrophils were compared in blood obtained simultaneously from venous and arterial sites before and 4 h after instillation of Streptococcus pneumoniae or Escherichia coli in rats.Measurements and Main Results: At 4 h of pneumonia, the number of neutrophils was greater in the venous blood entering the lungs than in the arterial blood leaving the lungs, indicating that neutrophil sequestration was occurring. More neutrophils entering the lungs contained F-actin rims than did neutrophils exiting, and the venous–arterial difference in F-actin–rimmed neutrophil counts completely accounted for sequestration. In E. coli pneumonia, in which neutrophil adhesion is mediated by CD11/CD18, CD18 blockade 15 min before blood samples were obtained did not prevent this sequestration of F-actin–rimmed neutrophils. Neutrophils expressing high or low levels of L-selectin or of neutrophils that bound platelets while circulating did not preferentially sequester.Conclusions: Neutrophils with cytoskeletal rearrangements preferentially sequester within the lungs during pneumonia, and this sequestration is not due to CD11/CD18-mediated adhesion, L-selectin expression, or platelet adhesion to neutrophils, suggesting that cytoskeletal rearrangements result in sequestration of neutrophils.