tbuckley/cabot-search huggingface dataset:
Safety and Efficacy of a Soluble P75 Tumor Necrosis Factor Receptor (Enbrel, Etanercept) in Patients With Advanced Heart Failure
Authors: Anita Deswal, Biykem Bozkurt, Yukihiro Seta, Semahat Parilti-Eiswirth, F. Ann Hayes, Consuelo Blosch, Douglas L. Mann
Journal: Circulation (1999)

Background —Although previous studies suggested that TNF may contribute to heart failure progression, it is unclear whether antagonizing TNF is beneficial in heart failure patients. Methods and Results —Eighteen NYHA class III heart failure patients were randomized into a double-blind dose-escalation study to examine the safety and potential efficacy of etanercept, a specific TNF antagonist (Enbrel). Patients received placebo (6 patients) or an escalating dose (1, 4, or 10 mg/m 2 ) of etanercept (12 patients) given as a single intravenous infusion. Safety parameters and patient functional status were assessed at baseline and at days 1, 2, 7, and 14. There were no significant side effects or clinically significant changes in laboratory indices. There was, however, a decrease in TNF bioactivity and a significant overall increase in quality-of-life scores, 6-minute walk distance, and ejection fraction in the cohort that received 4 or 10 mg/m 2 of etanercept; there was no significant change in these parameters in the placebo group. Conclusions —A single intravenous infusion of etanercept was safe and well tolerated in patients with NYHA class III heart failure. These studies provide provisional evidence that suggests that etanercept is sufficient to lower levels of biologically active TNF and may lead to improvement in the functional status of patients with heart failure.
Neural Control of Counter-Regulatory Events during Glucopenia in Man
Authors: Robert G. Brodows, F. Xavier Pi-Sunyer, Robert G. Campbell
Journal: Journal of Clinical Investigation (1973)

The effect of autonomic denervation on the metabolic and hormonal responses during intracellular glucopenia in man was investigated. 2-Deoxy-d-glucose (2 DG), a competitive inhibitor of glucose metabolism, was administered intravenously to nine normal volunteers and to five patients, three with complete cervical cord transection (C-6) and two with idiopathic orthostatic hypotension. Before, during, and after a 20 min infusion of 2 DG (50 mg/kg) plasma concentrations of glucose, lactate, FFA, total catecholamines, immunoreactive insulin (IRI), human growth hormone (HGH), and cortisol were determined for periods up to 150 min. In control subjects, the initial elevation of FFA, glucose. HGH, and cortisol corresponded with the rise in total catecholamines, with maximal levels attained at 60 min, lactate rose at a slower rate, reaching peak levels at 150 min: although no change in IRI was noted. In contrast, 2 DG-induced glucopenic stress in the autonomic denervated subjects was characterized by no detectable catecholamine release or significant rise in glucose, FFA, lactate, or IRI. However, HGH and cortisol responses in four of the five patients were of a similar or greater magnitude than controls.These studies demonstrate that the integrity of the sympathoadrenomedullary axis is essential for the counter-regulatory response to intracellular glucopenia in man. Cortisol and HGH have no apparent role in these events.
Change of Command in Combat: A Locus of Stress
Authors: DOUGLAS R. BEY
Journal: American Journal of Psychiatry (1972)

In the military a change of command is particularly stressful for the members of the unit involved. A comparison of units, some of which showed few increases in the indices of organizational stress and some of which showed great increases, revealed a relationship between the administrative style of the departing commander and the amount of stress experienced by the unit. The author describes methods used in the Army's First Infantry Division to help prevent excessive stress during the replacement period.
Long term effect of renal transplantation on dialysis-related amyloid deposits and symptomatology
Authors: Si-Yen Tan, Ashley Irish, Christopher G. Winearls, Edwina A. Brown, Peter E. Gower, Elaine J. Clutterbuck, Sheril Madhoo, J. Peter Lavender, Mark B. Pepys, Philip N. Hawkins
Journal: Kidney International (1996)
Mediastinitis After Coronary Artery Bypass Graft Surgery
Authors: Carmelo A. Milano, Karen Kesler, Nancy Archibald, Daniel J. Sexton, Robert H. Jones
Journal: Circulation (1995)

Background Mediastinitis is a severe complication of coronary artery bypass graft surgery (CABG). The purpose of the present study was to determine preoperative and intraoperative variables that predict mediastinitis and to determine the impact of this complication on long-term survival. Methods and Results Data on 20 preoperative and intraoperative variables were collected prospectively on 6459 consecutive patients who underwent CABG between January 1987 and January 1994. Eighty-three patients (1.3%) developed mediastinitis postoperatively, and a total of 24 patients (29%) died. Multivariate analysis identified 4 of the 20 variables as highly significant independent predictors for the development of mediastinitis: obesity ( P =.0002), New York Heart Association congestive heart failure class ( P =.002), previous heart surgery ( P =.008), and duration of cardiopulmonary bypass ( P =.05). A comprehensive review of the literature identified 13 other studies that evaluated 48 factors as predictors of mediastinitis; these data were critically analyzed and compared with the results from this series. In this series, postoperative interval mortality during the first 90 days after surgery for the patients with mediastinitis was 11.8% compared with 5.5% for the patients without mediastinitis. Interval mortality between 1 and 2 years after surgery remained high for the mediastinitis group (8.1%) relative to the nonmediastinitis group (2.3%). These differences were not eliminated by adjusting for important variables that influenced late survival in this population. Conclusions The present study and a review of the literature suggest that obesity and duration of surgery are the most important predictors of mediastinitis. Furthermore, although the early increase in mortality has been well described, the present study documents for the first time that mediastinitis has a significant negative influence on long-term survival independent of the patient’s preoperative condition.
Oral Contraceptives and Cardiovascular Disease
Authors: Bruce V. Stadel
Journal: New England Journal of Medicine (1981)

WHEN oral contraceptives became generally available during the early 1960s, their use increased rapidly, initially in North America and then elsewhere. By 1965, approximately 15 per cent of all married women 15 to 44 years of age in the United States were taking oral contraceptives; by 1973, this figure had increased to 25 per cent, or about 6.6 million.1 Use in the United States peaked during the mid-1970s but has continued to increase in many other countries.2 Worldwide, it is estimated that about 54 million women were using oral contraceptives by 1977. 2 Evidence suggesting that oral contraceptives might have effects . . .
The dependence of autologous chondrocyte transplantation on varying cellular passage, yield and culture duration
Authors: Gian M. Salzmann, Martin Sauerschnig, Markus T. Berninger, Theresa Kaltenhauser, Martin Schönfelder, Stephan Vogt, Gabriele Wexel, Thomas Tischer, Norbert Sudkamp, Philipp Niemeyer, Andreas B. Imhoff, Philip B. Schöttle
Journal: Biomaterials (2011)
Declining CD4 T-Cell Counts in a Person Infected with<i>nef</i>-Deleted HIV-1
Authors: Thomas C. Greenough, John L. Sullivan, Ronald C. Desrosiers
Journal: New England Journal of Medicine (1999)

To the Editor: We have recently seen declining CD4 T-lymphocyte counts in a man with long-term, nonprogressive infection with only nef-deleted forms of human immunodeficiency virus type 1 (HIV-1). ...
P10 Carboplatin and gemcitabine impair neutrophil phagocytic function
Authors: CR Popplewell, M-H Ruchaud-Sparagano, J Scott, PA Corris, AJ Simpson
Journal: Thorax (2013)

<h3>Background</h3> Lung cancer causes 6% of UK deaths with 20% due to infection<sup>1,2</sup>. The reason is multifactorial with myelosuppression secondary to chemotherapy being a contributor. However, the effect of chemotherapy drugs on the function of peripheral neutrophils has rarely been explored. It is proposed carboplatin and gemcitabine may decrease the function of circulating neutrophils that are present, causing a poorer response to infection by neutrophils that are present. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is used to stimulate neutrophil production in febrile neutropenic patients on chemotherapy, however studies show it also improves mature neutrophil function<sup>3,4</sup>. The aim was to research the effect of carboplatin and gemcitabine on neutrophil phagocytic function and to determine whether GM-CSF reverses any deficit seen in phagocytosis. <h3>Methods</h3> Neutrophils isolated from healthy donor blood by dextran sedimentation followed by discontinuous Percoll gradient. Untreated neutrophils compared with those pre-incubated with carboplatin, gemcitabine or both drugs (10<sup>-4</sup> mM). Phagocytosis assessed by ingestion of serum-opsonised zymosan. Repeated with 30 minute GM-CSF (5 ng/ml) pre-incubation. Apoptosis analysed by flow cytometry. All cells incubated for 2 hours untreated or with single or both chemotherapeutic agents (10<sup>-4</sup> mM) or phorbol 12-myristate 13-acetate (PMA) for 30 minutes. Cells stained with APC-Annexin V to detect apoptosis and propidium iodide to distinguish early and late apoptotic cells. <h3>Results</h3> A significant decrease in percentage phagocytosis occurred with chemotherapy drugs compared to untreated neutrophils: carboplatin p = &lt; 0.001, gemcitabine p = &lt; 0.01, carboplatin and gemcitabine p = &lt; 0.05. GM-CSF caused a significant increase in percentage phagocytosis when gemcitabine caused a deficit (p = &lt; 0.05) with a 9–13% increasing trend seen in other conditions. No difference in apoptosis occurred between untreated (median 3.9%) and chemotherapy treated neutrophils (median: carboplatin 4.4%, gemcitabine 4.9%, carboplatin and gemcitabine 3.6%). <h3>Conclusions</h3> This study demonstrated that phagocytosis is impaired by carboplatin and gemcitabine in healthy volunteer blood. Therefore it is proposed a reduced response to infection may also occur in lung cancer patients given these drugs, contributing to mortality. There was no difference in apoptosis, suggesting an alternative mechanism of action. Further study is required to explore the mechanism of action and the effect of GM-CSF on phagocytosis following chemotherapy. <h3>References</h3> Cancer Research UK. 2012 http://www.cancerresearchuk.org/cancer-info/cancerstats/types/lung/mortality/ Nichols L <i>et al</i>. <i>Arch Path Lab Med</i> 2012;136:1552–7 American Society of Clinical Oncology. <i>JCO</i> 2006;24:3187–205 Bober LA <i>et al.</i><i>Immunopharmacology</i> 1995;29:111–9
Control of Population
Authors: F. Roberts
Journal: BMJ (1961)

In the early years of this century it became obvious to demographers that the population of Western Europe was increasing only because of longer survival, and that if the continuing fall in the birth rate was not reversed a decline was inevitable. This prediction was most forcibly expressed by Spengler (1917), who saw in this metaphysical turn towards death a portent of the eventual extinction of Western civilization. Many British writers supported Spengler's contention. During the first world war public meetings were held urgently advocating the production of more children, but a people disillusioned as to the worth of human life by the holo caust then occurring on the Western Front received this exhortation with cynical derision.
Biochemical Tests and Pulmonary Infarction
Authors: L. A. otuama
Journal: BMJ (1966)

BEIAL JOURAL 1539scoliosis by a group, including an orthopaedic surgeon, an anatomist, a neurologist, a path- ologist, a radiologist, and perhaps an engineer with knowledge of the properties of materials and of stresses and strains.When the distorting forces causing scoliosis are further understood it will be much easier to determine their origin.The beginnings of such a study have already been started at the Brompton Hospital, and will soon be extended.I would welcome hearing from anyone interested in these wider aspects of this problem.-I am, etc.,
Use of secondary prophylaxis against myocardial infarction in the north of England.
Authors: M. Eccles, C. Bradshaw
Journal: BMJ (1991)

OBJECTIVE--To record the use of secondary prophylactic drugs in patients discharged from hospital having had a myocardial infarction. DESIGN--Prospective postal questionnaire survey of a random one in two sample of general practitioners in the region. SETTING--The nine family practitioner committee areas within the Northern Regional Health Authority. PATIENTS--Patients who had had a myocardial infarction and were discharged to their general practitioner. MAIN OUTCOME MEASURE--Whether beta blockers or aspirin, or both, were given on discharge. RESULTS--Of 267 patients, 158 (59%) were treated suboptimally in that they did not receive a secondary prophylactic drug to which they had no contraindication. For most patients this entailed underuse of one drug, but 17 (6%) of patients received no treatment. beta Blockers were 2.5 times less likely to be used than aspirin. Treatment was not associated with the age or sex of the patient, risk of further infarction, or hospital of discharge. CONCLUSIONS--Secondary prophylaxis after myocardial infarction is practised haphazardly. It should be offered to all patients who can tolerate it, after a trial period to assess any side effects of the drugs if necessary.
Cross-resistance between cisplatin, antimony potassium tartrate, and arsenite in human tumor cells.
Authors: P Naredi, D D Heath, R E Enns, S B Howell
Journal: Journal of Clinical Investigation (1995)

Cross-resistance between cisplatin (DDP) and metalloid salts in human cells was sought on the basis that mechanisms that mediate metalloid salt cross-resistance in prokaryotes are evolutionarily conserved. Two ovarian and two head and neck carcinoma cell lines selected for DDP resistance were found to be cross-resistant to antimony potassium tartrate, which contains trivalent antimony. The DDP-resistant variant 2008/A was also cross-resistant to arsenite but not to stibogluconate, which contains pentavalent antimony. A variant selected for resistance to antimony potassium tartrate was cross-resistant to DDP and arsenite. Resistance to antimony potassium tartrate and arsenite was of a similar magnitude (3-7-fold), whereas the level of resistance to DDP was greater (17-fold), irrespective of whether the cells were selected by exposure to DDP or to antimony potassium tartrate. In the resistant sublines, uptake of [3H]-dichloro(ethylenediamine) platinum(II) was reduced to 41-52% of control, and a similar deficit was observed in the accumulation of arsenite. We conclude that DDP, antimony potassium tartrate, and arsenite all share a common mechanism of resistance in human cells and that this is due in part to an accumulation defect.
Specific removal of in vivo antibody by extracorporeal circulation over an immunoadsorbent in gel
Authors: Isaac Schenkein, Jean-Claude Bystryn, Jonathan W. Uhr
Journal: Journal of Clinical Investigation (1971)

A method is described for preparation of a solid immunoadsorbent suspended in an agar gel. The immunoadsorbent in gel retains its specificity. Rabbits were injected with antibody or antigen, and an extracorporeal circulation was established through columns or funnels coated with such immunoadsorbents. It was shown that either antibody or antigen can be specifically and rapidly removed, and that no measurable amounts of antigen from the immunoadsorbent were released into the animals.
Physical Performance as Influenced by Oxygen and Fructose
Authors: L. M. Hursh
Journal: JAMA (1965)

Today, many athletic teams attempt to improve performance by using oxygen during rest periods of games. Fructose, though still used by some, is much less popular today than in the past. For the most part, data supporting both practices are subjective. However, the demonstration by Weinstein et al 1 of the direct utilization of fructose by the muscle of an extremity, and the demonstration by Corkill and Nelson 2 of the enhanced utilization of glucose in the presence of fructose, lend credibility to this concept. The purpose of this study was to obtain objective data on the influence of oxygen and fructose.  Methods  The three-minute Harvard step-test 3 and the endurance step-test were utilized. The latter test correlates well with other measurements of performance, such as oxygen consumption and blood lactate levels. Motivation is not a factor with the three-minute test but does influence the endurance test. The subject stepped
FOCAL INTERSTITIAL NEPHRITIS IN THE CALF FOLLOWING INTERFERENCE WITH THE NORMAL INTAKE OF COLOSTRUM
Authors: Theobald Smith
Journal: The Journal of Experimental Medicine (1925)

An interstitial focal nephritis found in young calves during the 1st or later months of life, associated with or preceded by the invasion of a special, virulent type of Bacillus coli, may be produced by postponing the feeding of colostrum 24 to 36 hours, or by withholding it altogether. In the presence of a virulent type of Bacillus coli few calves completely deprived of colostrum survive the 1st week. Among the survivors, the spotted kidney, the result of Bacillus coli bacteriemia, is frequently encountered. Calves normally fed have not shown the spotted kidney, and such as have been killed early have had uniformly sterile kidneys.
Levels and Concentration Ratios of Polychlorinated Biphenyls and PolybrominatedDiphenyl Ethers in Serum and Breast Milk in Japanese Mothers
Authors: Kayoko Inoue, Kouji Harada, Katsunobu Takenaka, Shigeki Uehara, Makoto Kono, Takashi Shimizu, Takumi Takasuga, Kurunthachalam Senthilkumar, Fumiyoshi Yamashita, Akio Koizumi
Journal: Environmental Health Perspectives (2006)

Blood and/or breast milk have been used to assess human exposure to various environmental contaminants. Few studies have been available to compare the concentrations in one matrix with those in another. The goals of this study were to determine the current levels of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in Japanese women, with analysis of the effects of lifestyle and dietary habits on these levels, and to develop a quantitative structure-activity relationship (QSAR) with which to predict the ratio of serum concentration to breast milk concentration. We measured PBDEs and PCBs in 89 paired samples of serum and breast milk collected in four regions of Japan in 2005. The geometric means of the total concentrations of PBDE (13 congeners) in milk and serum were 1.56 and 2.89 ng/g lipid, respectively, whereas those of total PCBs (15 congeners) were 63.9 and 37.5 ng/g lipid, respectively. The major determinant of total PBDE concentration in serum and milk was the geographic area within Japan, whereas nursing duration was the major determinant of PCB concentration. BDE-209 was the most predominant PBDE congener in serum but not in milk. The excretion of BDE 209 in milk was lower than that of BDE 47 and BDE 153. QSAR analysis revealed that two parameters, calculated octanol/water partition and number of hydrogen-bond acceptors, were significant descriptors. During the first weeks of lactation, the predicted partitioning of PBDE and PCB congeners from serum to milk agreed with the observed values. However, the prediction became weaker after 10 weeks of nursing.
Complement-Mediated Mechanisms in Anti-GD2 Monoclonal Antibody Therapy of Murine Metastatic Cancer
Authors: Masaki Imai, Charles Landen, Rieko Ohta, Nai-Kong V. Cheung, Stephen Tomlinson
Journal: Cancer Research (2005)

The role of complement in antibody therapy of cancer is in general poorly understood. We used the EL4 syngeneic mouse model of metastatic lymphoma to investigate the role of complement in immunotherapy directed against GD2, a target of clinical relevance. IgG2a and IgM anti-GD2 therapy protected EL4-challenged mice from metastases and prolonged survival. Expression of CD59, an inhibitor of direct complement-mediated cytotoxicity (CMC), effectively protected EL4 cells from CMC in vitro but did not affect the outcome of monoclonal antibody therapy. Protection by IgG therapy was also unaffected in mice deficient in C3 or complement receptor 3 (CR3) but was almost completely abrogated in FcgammaR I/III-deficient mice. These data indicate a crucial role for antibody-dependent cell-mediated cytoxicity (ADCC). However, at lower doses of IgG, therapeutic effect was partially abrogated in C3-deficient mice, indicating complement-mediated enhancement of ADCC at limiting IgG concentration. In contrast to IgG, the therapeutic effect of IgM was completely abrogated in C3-deficient mice. High level expression of CD59 on EL4 did not influence IgM therapy, suggesting IgM functions by complement-dependent cell-mediated cytotoxicity (CDCC), a mechanism thought to be inactive against tumor cells. Thus, IgG and IgM can operate via different primary mechanisms of action, and CDCC and complement-dependent enhancement of ADCC mechanisms are operative in vivo. The effects of complement can be supplemental to other antibody-mediated mechanisms and likely have increased significance at limiting antibody concentration or low antigen density.
STUDIES IN RESPONSIVITY OF THE ADRENAL CORTEX IN SCHIZOPHRENIA
Authors: ROBERT DICKES, GERALD H. FLAMM, WENDELL BOWMAN, EDWARD B. HOLLANDER, HOWARD W. POTTER
Journal: American Journal of Psychiatry (1953)

Eleven chronically hospitalized schizophrenic patients, in good physical and nutritional health, were studied by hourly eosinophile and lymphocyte counts after injections of saline and ACTH on consecutive days. Wide variations in the fasting levels of these blood elements existed among different patients and in the same patients from day to day. Saline elicited variations in eosinophile counts so that 5 of 11 subjects showed decreases of 50% or more after 4 hours. The lymphocytes varied by at least 29% for each subject at some point in the study after saline was injected. The response of the eosinophiles to ACTH was greatest 3 hours after injection. Ten of the 11 subjects showed a 50% or more variation in eosinophiles at some point in the procedure. All 11 subjects had more than a 50% variation in their lymphocyte counts. The adrenal cortical response of the schizophrencis we have studied, as measured by the eosinophile and lymphocyte responses to ACTH and by physiological variation, falls within the normal range. Studies of the 17-ketosteroid and corticosteroid excretion after ACTH in 11 cases of acute schizophrenia also showed varying responses in different subjects.