tbuckley/cabot-search huggingface dataset:
Urinary sodium balance in patients with cirrhosis: Relationship to quantitative parameters of liver function
Authors: G Wensing, E Lotterer, I Link, E G Hahn, W E Fleig
Journal: Hepatology (1997)

The relationship between the impairment in hepatic and renal function in cirrhosis has not been well established. This study investigated urinary sodium excretion in comparison with quantitative parameters of liver function in 75 patients with various degrees of cirrhosis kept on a constant salt diet of 120 mmol/d for 5 days before the start of the study. The aminopyrine breath test (ABT), indocyanine green (ICG) elimination, galactose elimination capacity (GEC), and hepatic sorbitol elimination (HSE) served as quantitative parameters of liver function. Results for the quantitative tests were compared with those for the Child-Pugh score. Urinary sodium excretion showed a significant nonlinear relationship to ABT (r = .70; P &lt; .0001). Less-significant correlations were observed for ICG (r = .60), the Child-Pugh score (r = -.57), GEC (r = .44), and HSE (r = .34). Because a number of significant correlations were observed between the different liver function tests, multivariate analysis was used to further elucidate the relationship between hepatic function and sodium excretion. Only one independent predictor of urinary sodium excretion could be identified, and that was the ABT ( P &lt; .02). More than half of the nonascitic patients showed a urinary sodium excretion of less than 80% of dietary sodium intake, indicating impaired renal sodium handling in preascitic cirrhosis. Based on the 95% confidence interval (CI) for ABT of nonascitic patients with normal (mean ABT 0.56% dose × kg/mmol CO 2 ; 95% CI: 0.44 to 0.69) and reduced urinary sodium excretion (mean ABT 0.26% dose × kg/mmol CO 2 ; 95% CI: 0.18 to 0.35), a threshold level of ABT of about 0.4 (% dose × kg/mmol CO 2 ) for conservation of normal urinary sodium excretion in cirrhosis can be defined. This ABT value reflects an approximate 50% reduction in function compared with the mean of cirrhotic patients with normal liver and kidney function (0.81% dose × kg/mmol CO 2 ). The presence of ascites was also associated with a reduction in ABT to below 0.4 (% dose × kg/mmol CO 2 ), while, for all other parameters, either the cut-off point was close to the lower limit of normal or no cut-off level could be detected. In conclusion, the results of the present study provide further evidence that the impairment in urinary sodium excretion in cirrhosis is related to hepatic function. The data suggest a nonlinear relationship. Because ABT has been shown to reflect functional hepatocellular mass, the occurrence of sodium retention and ascites appears to be related to a threshold of an approximate 50% reduction in functional liver cell mass.
Abstract LB-397: Functional characterization of IGF-1R antibodies and possible implications for clinical safety and efficacy
Authors: Klaus-Peter Kuenkele, Marco H. Hofmann, Stefan Scheiblich, Katharina Wartha, Christian Klein
Journal: Cancer Research (2011)

Abstract Background This is the first study performing a head to head comparison of monoclonal IGF-1R antibodies (mAb) based on published sequences for therapeutic mAbs from Pfizer (CP751,871, IgG2 kappa), Amgen (AMG479, IgG1 lambda), Merck (h7C10, cloned to R1507 backbone), Imclone (IMC-A12, IgG1 lambda) and Roche (R1507, IgG1). Methods In this study, sequence information for IGF-1R mAbs was extracted from patents and used to clone and transiently express IgGs (*=re-synthesized) in HEK293F cells. In vitro assays for ligand binding, IGF-1R auto-phosphorylation, IGF-1R downregulation, IR co-downregulation, and affinity analyses (Biacore) were used. In vivo comparison was done in BxPC3 xenograft mouse model. Results All antibodies inhibit IGF-1 binding and signaling at low nanomolar levels. While IMC-A12* and R1507 also prevent IGF-2 binding to IGF-1R and subsequent receptor activation, CP751,871* and h7C10* do not inhibit IGF-2 binding and have only limited impact (55%/30% inhibition) on IGF-2 signaling. Analysis of IGF-1R phosphorylation in 0.5 % FCS medium revealed that all antibodies except R1507 exert agonistic activity. Interestingly, Fab fragments of agonistic mAbs became antagonistic, indicating that bivalent binding is necessary for agonistic effects. All mAb (200nM, 24h treatment of MCF-7 cells) with the exception of AMG479* efficiently downregulated 78–82% the IGF-1R. Analysis of the same cell lysates revealed however striking differences in IR co-downregulation, a mechanism discussed as possible cause of clinical hyperglycemia. R1507 had the least side effects on Insulin co-downregulation (9%) compared to h7C10* (15%), CP751,871* (23%) and IMC-A12* (46%). Differences were also seen in the binding kinetics. Both AMG479* and R1507 showed faster koff rates resulting in shorter retention times at the receptor. Since kon/koff rates are discussed to influence tumor penetration (1), we compared downregulation of IGF-1R by R1507 and CP751,871* in xenograft tumors. Although both mAbs downregulate IGF-1R in vitro to the same extent, R1507 was significantly more effective in the in-vivo setting. Conclusion The head to head comparison of IGF-1R mAbs revealed differences in regard to binding properties, tumor penetration, IR codownregulation, and inhibition of signaling via the ligand IGF-2. Reference List 1. Adams, G. P., Schier, R., McCall, A. M., Simmons, H. H., Horak, E. M., Alpaugh, R. K., Marks, J. D., and Weiner, L. M. (2001) Cancer Res. 61, 4750–4755 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-397. doi:10.1158/1538-7445.AM2011-LB-397
Large scale food retail interventions and diet
Authors: Steven Cummins, Mark Petticrew, Leigh Sparks, Anne Findlay
Journal: BMJ (2005)

The ways in which nursing teams in the nurse led units make decisions about discharge also need to be explored.Nurses may, rightly or wrongly, be more conservative in discharging patients.They may err on the side of caution, but the benefits of these conservative decisions can only be judged with longer term follow up.Do these two new studies help us understand the differences between medical and nursing care?We think they usefully remind us that nursing care is not necessarily less costly and that the extra costs may be worth the benefits but that health outcomes need to be measured carefully in studies of sufficient power.It should not be assumed that the outcomes of nursing and medical care are equivalent.The skills of healthcare professionals and their assistants are much in demand and constitute a limited resource that needs to be deployed in the most cost effective way.Although UK health policy supports the development of nursing roles, as nurses take on more duties and responsibilities we must also question what, if anything, is being lost from nursing, to whom and does it matter?
Ascites and renal failure in primary liver cell carcinoma.
Authors: A Mas, V Arroyo, J Rodes, J Bosch
Journal: BMJ (1975)

Ascites and Renal Failure in Primary Liver Cell Carcinoma Ascites appears in 50-75% of patients with primary liver cell carcinoma (P.L.C.C.)' but there have been few investigations of its cause.We studied 25 patients with P.L.C.C. and ascites to assess any renal disturbances present.
After Bangkok — Expanding the Global Response to AIDS
Authors: Robert Steinbrook
Journal: New England Journal of Medicine (2004)

The progress that has been made in the global response to AIDS is real — but inadequate. An estimated 1 million people throughout the world are now using antiretroviral medications for human immunodeficiency virus (HIV) infection — double the number who were receiving such treatment two years ago. As of June 2004, 440,000 people from low- and middle-income countries were being treated.1 About 125,000 were from sub-Saharan Africa, where the burden is the greatest, an increase of 100,000 in two years. Spending on AIDS in low- and middle-income countries has increased from $1.0 billion in 2000 to $3.9 billion in . . .
Managing chronic diseases
Authors: John Reiss
Journal: BMJ (2005)

Managing chronic diseases Palliative care spectrum starts early onEditor-Palliative care does not start when a patient is dying. 1 A whole spectrum of palliation begins from the day of diagnosis of a potentially terminal disease, such as soft tissue sarcoma.Palliation, in the sense of needing to absorb what this means for the patient, becomes even then a medical imperative.The "How long have I got, Doc?" question may not be articulated, but it will be there and needs an empathetic response.Curative treatment is sought, but-with sarcoma-lung metastases signal the end of that phase and the beginning of palliative treatment.The doctor and the patient know the dragon can be disabled but never slain.Palliation is then partnership, working to decide what may be gained at what cost.(This may apply during curative treatment: to take chemotherapy drugs now "just in case," or to keep them for later?)Palliative treatment can be long (in sarcoma up to 20 years or more), or it can be brief.Its ending is not solely a medical judgment.Doctors may decide they can do no more, but active patients use online support groups, seeking new treatment options across the world.Patients may decide to end palliative treatment.Grown weary of painful chemotherapy offering diminishing returns, they may prefer a shorter but better life.Making that choice together is an aspect of palliation.When death is near, palliative care becomes terminal care.If throughout doctors and patients have aligned their understanding of the disease, and have taken decisions jointly, have explored the holistic meaning of disease in life and death, the palliative spectrum may offer healing if not cure.If, however, being palliative begins only when the patient is dying doctors cannot then meet patients, where they are most needed, in the ground of their being and their not being.
CELLULAR RECOGNITION BY MOUSE LYMPHOCYTES IN VITRO
Authors: W. H. Adler, T. Takiguchi, B. Marsh, R. T. Smith
Journal: The Journal of Experimental Medicine (1970)

The media and culture conditions required for in vitro stimulation of mouse lymphoid cells are described. The medium was arginine-rich and contained heat-inactivated human serum. A component of the human sera necessary for stimulation of the cells was a natural mouse cell agglutinin, which affected both background stimulation and the degree of induced stimulation with phytohemagglutinin (PHA). Absorption of the agglutinin from the human serum rendered the medium incapable of sustaining DNA synthesis in the presence of PHA. The response to PHA of mouse spleen and thymus cells was age-dependent and, although this response was not present at birth, it rapidly rose to adult levels. Spleen cells from mice immunized with bacillus Calmette-Guérin (BCG) or sheep erythrocytes (SRBC) showed increased in vitro reactivity to added purified protein derivative (PPD) or SRBC stroma, dependent on the time of immunization. The dose response curve for the SRBC stroma stimulated, immune spleen cells is compatible with a theory of cell to cell interaction being necessary for an in vitro reaction to antigen. The possible role of the mouse cell agglutinin (AMLG) is discussed.
HuR regulates gap junctional intercellular communication by controlling β-catenin levels and adherens junction integrity
Authors: Niloofar Ale-Agha, Stefanie Galban, Christiane Sobieroy, Kotb Abdelmohsen, Myriam Gorospe, Helmut Sies, Lars Oliver Klotz
Journal: Hepatology (2009)

Gap junctional intercellular communication (GJIC) plays a critical role in the regulation of tissue homeostasis and carcinogenesis and is modulated by the levels, subcellular localization, and posttranslational modification of gap junction proteins, the connexins (Cx). Here, using oval cell-like rat liver epithelial cells, we demonstrate that the RNA-binding protein HuR promotes GJIC through two mechanisms. First, HuR silencing lowered the levels of Cx43 protein and Cx43 messenger RNA (mRNA), and decreased Cx43 mRNA half-life. This regulation was likely due to the direct stabilization of Cx43 mRNA by HuR, because HuR associated directly with Cx43 mRNA, a transcript that bears signature adenylate-uridylate-rich (AU-rich) and uridylate-rich (U-rich) sequences in its 3'-untranslated region. Second, HuR silencing reduced both half-life and the levels of beta-catenin mRNA, also a target of HuR; accordingly, HuR silencing lowered the levels of whole-cell and membrane-associated beta-catenin. Coimmunoprecipitation experiments showed a direct interaction between beta-catenin and Cx43. Small interfering RNA (siRNA)-mediated depletion of beta-catenin recapitulated the effects of decreasing HuR levels: it attenuated GJIC, decreased Cx43 levels, and redistributed Cx43 to the cytoplasm, suggesting that depletion of beta-catenin in HuR-silenced cells contributed to lowering Cx43 levels at the membrane. Finally, HuR was demonstrated to support GJIC after exposure to a genotoxic agent, doxorubicin, or an inducer of differentiation processes, retinoic acid, thus pointing to a crucial role of HuR in the cellular response to stress and in physiological processes modulated by GJIC.HuR promotes gap junctional intercellular communication in rat liver epithelial cells through two related regulatory processes, by enhancing the expression of Cx43 and by increasing the expression of beta-catenin, which, in turn, interacts with Cx43 and is required for proper positioning of Cx43 at the plasma membrane.
Polyglandular Failure Syndrome
Authors: NADIR R. FARID
Journal: Annals of Internal Medicine (1980)

Letters1 March 1980Polyglandular Failure SyndromeNADIR R. FARID, M.B.B.S.NADIR R. FARID, M.B.B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-92-3-442_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The interesting article by Eisenbarth and colleagues (1) on the polyglandular failure syndrome raises a number of issues that bear discussion. First, because this clinical entity is rare, a variable degree of bias in the selection of a series of patients for study is unavailable. If large series of patients suffering from one autoimmune endocrine disease are examined, as we and Bottazzo (2) have done, for the concurrence of other disorders, a tendency towards ascertainment of a high proportion of patients suffering from insulin-dependent diabetes mellitus is seen. This may be due to selection bias or may...References1. EISENBARTHWILSONWARDBUCKLEYLEBOVITZ GPFCH. The polyglandular failure syndrome: disease inheritance, HLA type, and immune function. Ann Intern Med. 1979;91:528-33. LinkGoogle Scholar2. BOTTAZZOCUDWORTHMOULDONIACHFESTENSTEIN GADDH. Evidence for a primary autoimmune type of diabetes mellitus. Br Med J 1978;2:1253-5. CrossrefMedlineGoogle Scholar3. FARID N. Human leukocyte antigens (HLA) in endocrine disease. Can Med Assoc J. In press. Google Scholar4. UNGARMATHEWSTAITCOWLING BJBD. HLA patterns in pernicious anaemia. Br Med J. 1977;1:798-800. CrossrefMedlineGoogle Scholar5. FARIDMOENS NH. HLA haplotypes in familial Graves' disease. In: Proceedings of the Symposium on Autoimmune Aspects of Endocrine Disorders. New York: Academic Press; 1979: In press. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: NADIR R. FARID, M.B.B.S.Affiliations: Health Sciences Center St. John's NF A1B 3V6 Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEndocrinology 1 March 1980Volume 92, Issue 3Page: 442-443KeywordsAutoimmune diseasesDiabetes mellitusInsulin ePublished: 1 December 2008 Issue Published: 1 March 1980 PDF downloadLoading ...
Educational Programs in US Medical Schools, 2002-2003
Authors: Barbara Barzansky
Journal: JAMA (2003)

To better provide medical students with the knowledge, skills, attitudes, and values they will need as physicians, US medical schools continue to make ongoing changes to their staffing and curricula.To review the status of US medical education in the 2002-2003 academic year, compared with 1997-1998.The Liaison Committee on Medical Education (LCME) Annual Medical School Questionnaire, the Association of American Medical Colleges (AAMC) Databook, and the AAMC Data Warehouse: Applicant Matriculant File. Data evaluated included those on medical school faculty, applicants, and students; curriculum hours devoted to new multidisciplinary or nontraditional subject areas (eg, cultural diversity, evidence-based medicine, medical ethics, medical informatics); and methods used to evaluate student learning.The number of full-time faculty members in the 126 LCME-accredited medical schools increased from 96 773 in 1997-1998 to 109 526 in 2002-2003 (+13.2%). The number of applicants entering decreased from 43 016 in 1997-1998 to 33 625 in 2002-2003 (-21.8%). The number of enrollees remained virtually unchanged from 1997-1998 (66 748) to 2002-2003 (66 677). Most medical schools have incorporated new subject areas into their curricula, although time devoted to these areas varies across schools. Schools typically use written examinations (National Board of Medical Examiners subject tests and/or internally prepared examinations) to assess factual knowledge, and observations by faculty members and residents to assess clinical skills. Use of standardized methods (eg, an objective structured clinical examination [OSCE]) to assess clinical skills is variable; 82 schools use a final third- or fourth-year comprehensive OSCE; 53 require a passing OSCE score for graduation.While the number of applicants to US medical schools has continued to decline, student numbers are constant. The number of full-time faculty members has increased. Schools are incorporating new subject areas into their curricula, and the use of standardized methods of assessing clinical skills, while variable, is generally increasing.
Prevalence of hereditary hemochromatosis in a Massachusetts corporation: Is Celtic origin a risk factor?
Authors: B N Smith, W Kantrowitz, N D Grace, M S Greenberg, T J Patton, R Ookubo, K Sorger, J G Semeraro, J R Doyle, A G Cooper, B R Kamat, L M Maregni, W M Rand
Journal: Hepatology (1997)

The prevalence of homozygous hereditary hemochromatosis (HHC) is estimated at 1:250 in Caucasian adults. Little is known about ethnic subpopulations that might be at increased risk for this disease. HLA data have suggested a Celtic origin for HHC. Screening for HHC was offered to all employees of the Massachusetts Polaroid Corporation. Participants with a transferrin saturation of >55% or >45% and an elevated serum ferritin concentration on two screenings were referred for liver biopsy. The diagnosis of HHC was based on histological criteria, quantitative hepatic iron determination, hepatic iron index, and the phlebotomy requirement for iron depletion. Participants completed a questionnaire regarding their ethnic background. Two thousand two hundred ninety-four employees were screened, and 5 cases of HHC were detected. All 5 cases involved Caucasian men, yielding a prevalence of 1:395 for the Caucasian population. Four of the 5 cases were of 100% British-Irish ancestry based on the country of origin of their grandparents. Additional analysis revealed that the majority of grandparents of all 4 individuals came from Ireland or Wales. The exact two-tailed trend test showed a significant association of HHC with Celtic background (P = .012). The estimated cost of screening per patient identified was $18,041. Polaroid Corporation has a high representation of employees of British-Irish ancestry. Our data suggest that they are at high risk for developing HHC. A significant association of HHC with Celtic ancestry was found in this subpopulation, supporting the concept of a Celtic origin for this disease.
The Challenges of Intracranial Revascularization for Stroke Prevention
Authors: Joseph P. Broderick
Journal: New England Journal of Medicine (2011)

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial1 (SAMMPRIS, ClinicalTrials.gov number, NCT00576693), as reported by Chimowitz et al. in this issue of the Journal, showed that aggressive medical management alone was superior to intracranial arterial stenting with the use of the Wingspan stent system in addition to aggressive medical therapy in patients with a recent transient ischemic attack or stroke attributed to 70 to 99% stenosis of the diameter of a major intracranial artery. Three key lessons can be gleaned from the SAMMPRIS trial and previous trials of revascularization for stroke prevention: the challenges . . .
Understanding the role of the doctor
Authors: F. Godlee
Journal: BMJ (2008)

A united view from the profession brings us closer

What is the role of the doctor? So asked Sir John Tooke, chair of the Medical Schools Council, in last year’s inquiry into UK doctors’ specialist training.1 As Tooke said, without clarity on the doctor’s role, we can’t know how best we should select, educate, and train doctors, or plan the future medical workforce. We have now received the profession’s answer—a consensus statement endorsed by a consortium of leaders of UK medicine.2

This isn’t the first attempt to define what it means to be a doctor. Nor will it be the last. The International Labour Organisation (ILO) is updating its definition (box), and the World Health Organization and the Organisation for Economic Cooperation and Development are drawing up their own. Many forces have converged to prompt these efforts: sociopolitical changes; scientific and technical progress; the end of deference and the democratisation of knowledge; the rise of chronic disease; and the shift to multidisciplinary working, including role substitution and the extended role of nurses.

These were among the factors that prompted the Royal College of Physicians’ 2005 inquiry into the meaning of professionalism. Its report defined professionalism as “a set of values, behaviours, and relationships that underpins the trust the public has in doctors.”3 …
VI. University of Kansas Medical Center Family Practice Residency
Authors: Jesse D. Rising
Journal: JAMA (1961)

THE FAMILY practice residency at the University of Kansas Medical Center is designed to provide training for future family physicians in accordance with the philosophy and recommendations of the Committee on Preparation for General Practice as approved by the American Medical Association. It is important to recognize that this basic program is conceived in its entirety, and that it emphasizes experience in a few broad areas with sufficient time devoted to each to give experience in depth. The concept of continuity on a service and continuity in patient care is stressed. The program, in order to stay within the 2-year time limit, and in order to remain a basic one meeting the needs of all family physicians, does not include experience in some areas. This is, then, a basic, minimal program which represents an extension of only one year over the time currently spent in the internship. It is patently
New medical bill could tackle education
Authors: J. Warden
Journal: BMJ (1994)

Legislation to protect patients in Britain from doctors who perform badly is likely to be shelved for another year. Instead of a bill being introduced this autumn, the NHS Executive now gives October 1995 as the target date for amending the 1983 Medical Act. The amendments will give the General Medical Council (GMC) statutory powers to deal with incompetent doctors whose performance does not amount to serious professional misconduct.

But the planned new bill will go beyond the original GMC proposals. It will also implement changes in medical education …