tbuckley/cabot-search huggingface dataset:
Can Postprandial Blood Glucose Excursion Be Predicted in Type 2 Diabetes?
Authors: Sylvia Franc, Dured Dardari, Caroline Peschard, Jean-Pierre Riveline, Magdalena Biedzinski, Beatrix Boucherie, Catherine Petit, Elisabeth Requeda, Frederic Mistretta, Michel Varroud-Vial, Guillaume Charpentier
Journal: Diabetes Care (2010)

We investigated the relationship between carbohydrate intake and postprandial blood glucose (BG) levels to determine the most influential meal for type 2 diabetic subjects treated with basal insulin and needing prandial insulin.Three-day BG profiles for 37 type 2 diabetic subjects, with A1C levels of 7.7%, treated with sulfonylurea and metformin, and well titrated on insulin glargine, were analyzed using a continuous glucose monitoring system. Food intake from 680 meals was recorded and quantified during continuous glucose monitoring.The median BG excursion (DeltaBG) was higher at breakfast than at lunch or dinner (111 [81; 160] vs. 69.5 [41.5; 106] and 82.5 mg/dl [53; 119] mg/dl, P < 0.0001). There was a weak overall correlation between DeltaBG and carbohydrate intake. Correlation improved when mealtime was taken into account. Simple relationships were established: DeltaBG (mg/dl) = 65 x carbohydrate/body weight + 73 for breakfast (R(2) = 0.20, P < 0.0001); the slope was reduced by half at lunch and by one-third at dinner. Twelve relevant variables likely to affect DeltaBG were integrated into a polynomial equation. This model accounted for 49% of DeltaBG variability. Two groups of patients were identified: responders, in whom DeltaBG was well correlated with carbohydrate intake (R(2) >or= 0.30, n = 8), and nonresponders (R(2) < 0.30, n = 29). Responders exhibited a greater insulinopenic profile than nonresponders.The carbohydrate intake in responders clearly drives DeltaBG, whereas, in nonresponders, other factors predominate. This sort of characterization should be used to guide therapeutic choices toward more targeted care with improved type 2 diabetes management.
Ethanol impairs post-prandial hepatic protein metabolism.
Authors: P De Feo, E Volpi, P Lucidi, G Cruciani, F Monacchia, G Reboldi, F Santeusanio, G B Bolli, P Brunetti
Journal: Journal of Clinical Investigation (1995)

The effects of acute ethanol ingestion on whole body and hepatic protein metabolism in humans are not known. To simulate social drinking, we compared the effects of the association of a mixed meal (632 kcal, 17% amino acids, 50% glucose, 33% lipids) with a bottle of either table wine (ethanol content 71 g) or water on the estimates ([1-14C]-leucine infusion) of whole body protein breakdown, oxidation, and synthesis, and on the intravascular fractional secretory rates (FSR) of hepatically (albumin, fibrinogen) and extrahepatically (IgG) synthesized plasma proteins in two randomized groups (ethanol n = 7, water n = 7) of healthy nonalcoholic volunteers. Each study was carried out for 8 h. Protein kinetics were measured in the overnight post-absorptive state, over the first 4 h, and during a meal infusion (via a nasogastric feeding tube at constant rate) combined with the oral ingestion of wine or water, over the last 4 h. When compared with water, wine ingestion during the meal reduced (P < 0.03) by 24% the rate of leucine oxidation, did not modify the estimates of whole body protein breakdown and synthesis, reduced (P < 0.01) by approximately 30% the FSR of albumin and fibrinogen, but did not affect IgG FSR. In conclusion, 70 g of ethanol, an amount usual among social drinkers, impairs hepatic protein metabolism. The habitual consumption of such amounts by reducing the synthesis and/or secretion of hepatic proteins might lead to the progressive development of liver injury and to hypoalbuminemia also in the absence of protein malnutrition.
Series on education: How should we be teaching our undergraduates?
Authors: J. E Dacre
Journal: Annals of the Rheumatic Diseases (2000)

Medical education has changed significantly over the past two decades in many European countries. Rheumatologists have kept up to date with this change by becoming involved in curricular reform, and with the development of national,1 and European2 rheumatology curricula for undergraduate and postgraduate education Most of the examples of change cited in this article are based on the UK medical schools, but it is likely that these changes are reflected in other European countries. In addition, medical schools are in the midst of the implementation of substantial reforms of their own curricula after the General Medical Council recommendations.3 The quality of rheumatology teaching is in the process of being evaluated as part of the Quality Assurance Agency visits, and there is likely to be an increasing demand for teachers in higher education (including medicine) to be trained following the Dearing report.4 Provided that we can continue to keep abreast of these changes the standard of undergraduate teaching in rheumatology will improve considerably.

One of the current themes of medical education is that it has become recognised as a lifelong process.5 Our undergraduates need to acquire learning skills that will take them from their undergraduate experience, through their general clinical training, specialist registrar training, and continuing medical education as consultant rheumatologists. Another theme is the shift from a teacher centred approach, where the emphasis is on the teachers and what they do, to a learner centred approach, where the emphasis is on what the students learn. To achieve this shift, a learning facilitator replaces the traditional didactic teacher, and traditional didactic teaching methods are replaced by interactive teaching in smaller groups.

The principles behind these methods are based on a body of educational research that has identified characteristics related to effective university teaching and learning. The …
EXPERIMENTAL YAWS IN THE MONKEY AND RABBIT
Authors: Henry J. Nichols
Journal: The Journal of Experimental Medicine (1910)

1. Rabbits can be infected in the testicle with the spirochetæ of yaws as well as with those of syphilis and the infection can be continued through successive generations in pure culture. 2. The infection shows itself by enlargement of the testicle and the presence of a nodule varying in size from that of a pea to that of an olive. The infection consists in a necrosis of the tubules, an infiltration of round cells and the new formation of an edematous connective tissue. 3. The complement fixation reaction occurs in rabbits infected with the spirochetæ of yaws as well as in those infected with the spirochetæ of syphilis. 4. This lesion makes possible the investigation of the problems of cultivation, of immunity and of treatment.
Risk of serious adverse reactions during the treatment of new tuberculosis patients
Authors: Diana Ivanova, Serge Borisov, Alexander Ryzhov
Journal: European Respiratory Journal (2012)

Background:  Treatment of tuberculosis (TB) may be complicated by serious adverse reactions (SADRs). Correct risk assessment before the start of treatment enables to choose the right preventive strategy and thereby to reduce a frequency of SADRs. The aim was to determine the rates of and risk factors for SADRs during treatment of new TB patients.  Methods  200 HIV-uninfected new pulmonary TB patients admitted to Research and Clinical Center for TB control 2009 to 2011 were monitored for ADRs during the intensive phase of treatment. The median age was 28.0 (IQR 22-44) yrs, 93 were female, 108 were smear-positive, 172 received only first-line anti-TB drugs. ADRs having NCI CTCAE Grade 3-4 were recorded as serious. Multivariate logistic regression was used for risk assessment.  Results  Seventy-six (37.8%) experienced at least one SADR, to a total of 95 events (47 - hepatitis, 19 – allergic reactions, 14 - hyperuricemia, 7 – deafness). Female sex (OR = 2,11, 95%CI: 1.08-4.12), a smear-positive TB (OR = 2.08, 95%CI: 1.05-4.13), a cavity diameter > 30 mm (OR = 5.11, 95%CI: 1.44-18.12), a body mass index (BMI)   Conclusion  During anti-TB treatment more than the third part of new TB patients experienced SADRs (more often hepatitis and allergy). Female sex, a history of drug/food allergy, low BMI, smear-positive TB and large cavities are the risk factors associated with SADRs.
The Response to and Repair of RAG-Mediated DNA Double-Strand Breaks
Authors: Beth A. Helmink, Barry P. Sleckman
Journal: Annual Review of Immunology (2012)

Developing lymphocytes must assemble antigen receptor genes encoding the B cell and T cell receptors. This process is executed by the V(D)J recombination reaction, which can be divided into DNA cleavage and DNA joining steps. The former is carried out by a lymphocyte-specific RAG endonuclease, which mediates DNA cleavage at two recombining gene segments and their flanking RAG recognition sequences. RAG cleavage generates four broken DNA ends that are repaired by nonhomologous end joining forming coding and signal joints. On rare occasions, these DNA ends may join aberrantly forming chromosomal lesions such as translocations, deletions and inversions that have the potential to cause cellular transformation and lymphoid tumors. We discuss the activation of DNA damage responses by RAG-induced DSBs focusing on the component pathways that promote their normal repair and guard against their aberrant resolution. Moreover, we discuss how this DNA damage response impacts processes important for lymphocyte development.
Elimination of Neuroblastoma and Small-Cell Lung Cancer Cells With an Anti-Neural Cell Adhesion Molecule Immunotoxin
Authors: D. C. Roy, S. Ouellet, C. Le Houillier, P. D. Ariniello, C. Perreault, J. M. Lambert
Journal: JNCI Journal of the National Cancer Institute (1996)

The development of immunotoxins has been hampered by difficulties, particularly in solid tumors, of finding appropriate target antigens and of linking sufficiently potent toxins. We evaluated the tissue specificity of an immunotoxin, N901-blocked ricin (N901-bR), and assessed its potential for eliminating neural cell adhesion molecule (NCAM)-positive tumor cells in conditions appropriate for in vitro purging, prior to autologous stem cell transplantation, and its potential for myelosuppression. N901-bR consists of a monoclonal antibody (MAb), N901, directed against CD56, an antigen of the family of NCAMs, covalently linked to blocked ricin as the cytotoxic effector moiety. The tissue specificity of the N901 MAb and the N901-bR immunotoxin was tested against a wide array of human tumor tissues and normal human tissues by immunohistochemical staining. The cytotoxic activity of N901-bR was tested against both small-cell lung cancer (SCLC) cells and neuroblastoma cells, either alone or among normal bone marrow mononuclear cells, and the efficacy of this treatment to specifically eliminate these cells was evaluated in a limiting dilution assay. In addition, normal bone marrow mononuclear cells were incubated with N901-bR, and the toxic effects of the immunotoxin on normal hematopoietic progenitors was evaluated. N901 and N901-bR exhibited specificity for several neoplasms of neuroectodermal origin, including SCLC and neuroblastoma. Staining of normal tissues was essentially limited to various neuroendocrine cells, cardiac muscle cells, and cells in peripheral nerve tissue. We observed a time- and dose-dependent elimination of tumor cells in vitro, with three logs (i.e., >99.9%) of malignant cells being killed following only 5 hours of exposure to 10 n M N901-bR. Unconjugated N901 MAb specifically blocked the elimination of NCAM-positive cells by N901-bR, whereas neither an isotype-matched control MAb nor galactose (the ligand of native ricin) had any effect on the activity of the immunotoxin, confirming the specificity of its cytotoxic activity. Importantly, N901-bR used under optimal conditions for in vitro tumor cell depletion was not toxic to hematopoietic precursors. N901-bR has the properties required to target CD56, an antigen present not only on cells from a large number of cancers of neuroendocrine origin, but also on some important normal tissues. In addition, treatment with this immunotoxin results in the highly effective and specific elimination of neuroblastoma and SCLC cells and does not affect normal hematopoietic progenitors. N901-bR may have clinical utility for purging of neuroblastoma cells and SCLC cells before autologous stem cell transplantation. Further toxicology studies are warranted to assess the potential of N901-bR for in vivo administration.
Effects of Prostaglandin A <sub>1</sub> on the Systemic and Coronary Circulations in the Conscious Dog
Authors: CHARLES B. HIGGINS, STEPHEN F. VATNER, DEAN FRANKLIN, THOMAS PATRICK, EUGENE BRAUNWALD, DANIEL P. MCKOWN, DAVID HENDRICK
Journal: Circulation Research (1971)

The effects of intravenous prostaglandin A 1 (PGA 1 ) on systemic and coronary hemodynamics were studied in 13 intact, conscious dogs after recovery from operation for implantation of Doppler ultrasonic flow probes on the ascending aorta and left circumflex coronary artery. Graded doses of PGA 1 (0.01 to 1.0 µg/kg) caused arterial pressure and total systemic resistance to decrease progressively and heart rate and cardiac output to increase progressively. At the maximum dose administered (1.0 µg/kg), arterial pressure and systemic resistance decreased by averages of 30% and 51% below control, respectively, and heart rate and cardiac output rose 64% and 47%, respectively. After beta-receptor blockade with propranolol, PGA 1 still caused a similar increase in cardiac output. In spite of arterial hypotension, PGA 1 produced a progressive increase in coronary flow, with a peak increase of 74% above control with 1.0 µg/kg and a corresponding graded decrease in coronary resistance, with a decrease of 61% below control with 1.0 µg/kg. Marked increases occurred in systolic as well as diastolic coronary flow. The coronary vasodilation was not abolished by preventing the PGA 1 -induced tachycardia with electrical pacing, by beta-receptor blockade, or by combined blockade of beta receptors and cholinergic nerve fibers. While arterial Po 2 remained constant, coronary sinus Po 2 rose when coronary flow was increased by PGA 1 . Thus PGA 1 is both a primary and secondary coronary vasodilator which increases cardiac output and decreases total systemic resistance.
Rice bodies in the pleural aspirate of a patient with rheumatoid arthritis.
Authors: D Kassimos, E George, J R Kirwan
Journal: Annals of the Rheumatic Diseases (1994)

Frequencies ofHLA-A, B, C and DR antigens in patients with or without anti-Sm antibodies HLA Group A (Sm (+))Group B (Sm () Healthy controls antigens number (%)
A Genome-wide Pleiotropy Scan for Prostate Cancer Risk
Authors: Orestis A. Panagiotou, Ruth C. Travis, Daniele Campa, Sonja I. Berndt, Sara Lindstrom, Peter Kraft, Fredrick R. Schumacher, Afshan Siddiq, Stefania I. Papatheodorou, Janet L. Stanford, Demetrius Albanes, Jarmo Virtamo, Stephanie J. Weinstein, W. Ryan Diver, Susan M. Gapstur, Victoria L. Stevens, Heiner Boeing, H. Bas Bueno-de-Mesquita, Aurelio Barricarte Gurrea, Rudolf Kaaks, Kay-Tee Khaw, Vittorio Krogh, Kim Overvad, Elio Riboli, Dimitrios Trichopoulos, Edward Giovannucci, Meir Stampfer, Christopher Haiman, Brian Henderson, Loic Le Marchand, J. Michael Gaziano, David J. Hunter, Stella Koutros, Meredith Yeager, Robert N. Hoover, Stephen J. Chanock, Sholom Wacholder, Timothy J. Key, Konstantinos K. Tsilidis
Journal: European Urology (2014)
CD74: A New Candidate Target for the Immunotherapy of B-Cell Neoplasms
Authors: Rhona Stein, M. Jules Mattes, Thomas M. Cardillo, Hans J. Hansen, Chien-Hsing Chang, Jack Burton, Serengulam Govindan, David M. Goldenberg
Journal: Clinical Cancer Research (2007)

Abstract CD74 is an integral membrane protein that functions as a MHC class II chaperone. Moreover, it has recently been shown to have a role as an accessory-signaling molecule and has been implicated in malignant B-cell proliferation and survival. These biological functions combined with expression of CD74 on malignant B cells and limited expression on normal tissues implicate CD74 as a potential therapeutic target. The anti-CD74 monoclonal antibody LL1 has been humanized (hLL1 milatuzumab or IMMU-115) and can provide the basis for novel therapeutic approaches to B-cell malignancies, particularly because this antibody shows rapid internalization into CD74+ malignant cells. This article reviews the preclinical evaluations of LL1, its humanized form, and isotope, drug, and toxin conjugates. These studies show that unconjugated hLL1 and conjugates of hLL1 constructs with radioisotopes, doxorubicin, and frog RNase have high antitumor activity in non–Hodgkin's lymphoma and multiple myeloma in vitro and in tumor xenograft models. Single-dose studies of hLL1 in monkeys showed no adverse effects but did decrease circulating B and T lymphocytes and natural killer cells. When evaluated in combination with rituximab, either equivalent or improved efficacy, compared with either antibody alone, was observed. CD74 is a new candidate target for the immunotherapy of neoplasms expressing this antigen, which can be exploited using either a naked antibody or conjugated to isotopes, drugs, or toxins.
Male hormonal contraception: concept proven, product in sight?
Authors: Kati L. Matthiesson, Robert I. McLachlan
Journal: Human Reproduction Update (2006)

Current male hormonal contraceptive (MHC) regimens act at various levels within the hypothalamic pituitary testicular axis, principally to induce the withdrawal of the pituitary gonadotrophins and in turn intratesticular androgen production and spermatogenesis. Azoospermia or severe oligozoospermia result from the inhibition of spermatogonial maturation and sperm release (spermiation). All regimens include an androgen to maintain virilization, while in many the suppression of gonadotrophins/spermatogenesis is augmented by the addition of another anti-gonadotrophic agent (progestin, GnRH antagonist). The suppression of sperm concentration to 1 × 106/ml appears to provide comparable contraceptive efficacy to female hormonal methods, but the confidence intervals around these estimates remain relatively large, reflecting the limited number of exposure years reported. Also, inconsistencies in the rapidity and depth of spermatogenic suppression, potential for secondary escape of sperm into the ejaculate and onset of fertility return not readily explainable by analysis of subject serum hormone levels, germ cell number or intratesticular steroidogenesis, are apparent. As such, a better understanding of the endocrine and genetic regulation of spermatogenesis is necessary and may allow for new treatment paradigms. The development of an effective, consumer-friendly male contraceptive remains challenging, as it requires strong translational cooperation not only between basic scientists and clinicians but also between public and private sectors. At present, a prototype MHC product using a long-acting injectable testosterone and depot progestin is well advanced.
The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti–multiple myeloma (MM) activity and overcome bortezomib resistance
Authors: Dharminder Chauhan, Guilan Li, Klaus Podar, Teru Hideshima, Reshma Shringarpure, Laurence Catley, Constantine Mitsiades, Nikhil Munshi, Yu Tzu Tai, Nanjoo Suh, Gordon W. Gribble, Tadashi Honda, Robert Schlossman, Paul Richardson, Michael B. Sporn, Kenneth C. Anderson
Journal: Blood (2003)
HBsAg seroprevalence among Senegalese militaries
Authors: Abdoul A Ndiaye, Ibrahima Socé Fall, Gora Lo, Sidy Mouhamed Seck, Alioune Badara Tall, Boubacar Gueye, Amady Barro Mbodj, Anta Tal-Dia
Journal: Military Medical Research (2015)

Chronic hepatitis is a major public health problem. Hepatitis B virus is the primary cause, and Hepatitis B and C together are responsible for 60% of cirrhosis and 80% of hepatocellular carcinomas. This study measured the prevalence of HBsAg among Senegalese military to develop an appropriate strategy to prevent cirrhosis and hepatocellular carcinoma.We conducted a descriptive cross-sectional study among Senegalese military aged 25 to 60 years. A sample of 1224 participants was selected following a two-level-stratification. The mark of surface HBs antigen using chemiluminescence concerned 1195 participants. The presence of HBsAg was analyzed according to age, marital status, alcohol consumption and glomerular filtration rate. Epi-info6fr and R software were used, respectively, for data capture and analyses. A Chi-square test was performed to compare proportions considering a significance level of 5% and a confidence interval of 95%.The average age was 39.8 ± 9.2 years. Participants in the age groups of 25-34 years, 45-60 years and 35-44 years were respectively 30.7%, 34.4% and 34.9% of the sample. Married persons represented 82.6% of participants and 17.08% were single. Most participants were educated (99%), and 56% had reached at least secondary school level. Alcohol consumption was at 11.5%. The HBsAg prevalence rate was 10.8% [9.1% to 12.7%] with a significant difference between age groups (P < 0.001), which ranged from 5.6% for 45-60 years, 9.62% for 25-34 years to 16.9% for 35-44 years. Marital status and alcohol consumption did not affect the carriage of HBsAg. HBsAg prevalence was more common among participants who had a glomerular filtration rate greater than 90 ml/min. Transaminases rate exceeded the normal threshold for 43 participants (3.6%); the increase was 6.6% [2.7% to 11.8%] for HBsAg carriers and 3.2% [1.2% to 6.7%] for alcohol users.The high prevalence of HBsAg in the military requires the implementation of an effective prevention and care program to reduce the risk of cirrhosis and hepatocellular carcinoma and contribute to reducing the burden of communicable diseases, such as hepatitis and HIV/AIDS, and non-communicable diseases.
Epidemiology of rubella in Finland
Authors: I Davidkin, H Peltola, P Leinikki
Journal: Eurosurveillance (2004)

Before rubella vaccination programmes began, rubella infection was prevalent in Finnish children. The disease occurred as epidemics at intervals of a few years. Rubella infection was most often contracted between the ages of 2 and 12 years. Vaccinations specifically aimed at eradicating rubella were begun with monocomponent vaccine in the mid-1970s, and the measles, mumps and rubella (MMR) vaccination programme with two injections got underway in 1982. A clear reduction in rubella cases was evident a few years after the launch of the MMR programme. Owing to a sufficiently high vaccination coverage (>95% since 1987), circulation of the indigenous rubella virus in the Finnish population ceased in the late 1990s. Some rubella cases have been imported to Finland since elimination, but they have not caused any secondary cases. This shows unambiguously that protection against rubella continues to be effective, although our cohort studies imply that the vaccine induced antibody levels do decrease with time. The MMR programme has also eliminated congenital rubella syndrome (CRS) from the country. The last CRS case was recorded in 1986. As a result of the high coverage two dose MMR vaccination programme, rubella was successfully eliminated from Finland. How long the acquired protection will last remains to be seen.