tbuckley/cabot-search huggingface dataset:
Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating-factor support for dose-intensive cyclophosphamide, etoposide, and cisplatin
Authors: Jonathan C. Yau, James A. Neldhart, Pierre Triozzi, Shailendra Verma, John Nemunaitis, Donald P. Quick, David G. Mayernik, Dagmar H. Oette, Ann F. Hayes, John Holcenberg
Journal: American Journal of Hematology (1996)

This is a double-blind randomized placebo-controlled trial to evaluate the efficacy and safety of granulocyte-macrophage colony-stimulating-factor (GM-CSF) after dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). Fifty-six patients with lymphoma or breast carcinoma were randomized to receive GM-CSF 250 μg/m2 or placebo subcutaneously (SC) every 12 hr after each course of DICEP until recovery of absolute neutrophil count (ANC) of 1.5 × 109/L. Each patient was to receive three courses of DICEP. There were 28 patients in each group. The median duration of ANC below 0.5 × 109/L was 10 versus 12 days for Course 1 (P = 0.010), 10 versus 12 days for Courses 2 (P = 0.248), and 16.5 versus 15 days for Course 3 (P = 0.126); platelet counts below 20 × 109/L was 4 versus 4 days for Course 1 (P = 0.586), 8.5 versus 7 days for Course 2 (P = 0.013), and 23.5 versus 10.5 days for Course 3 (P = 0.104); hospitalization for patients readmitted with cytopenic fever were 4 versus 8 days for Course 1 (P = 0.035); 7 versus 6 days for Course 2 (P = 0.692); and 8 versus 12 days for Course 3 (P = 0.884) in the GM-CSF and placebo group, respectively. GM-CSF significantly shortens the duration of neutropenia and readmission only during the first course of DICEP. There was a delay in platelet recovery and an increase in transfusion requirement during subsequent courses in the GM-CSF group. The result cautions the routine use of lineage specific hematopoietic growth factors in supporting repeated cycles of dose-intensive chemotherapy. © 1996 Wiley-Liss, Inc.
Cutaneous Larva Migrans
Authors: Chia Chun Ang
Journal: New England Journal of Medicine (2010)

A 42-year-old man presented with a 1-week history of intensely pruritic eruption on the dorsum of his right foot. He had gone for a barefoot stroll on the beach a few days before the onset of serpiginous, erythematous raised tracts with bulla formation.
Myocardial ischemia induces differential regulation of KATP channel gene expression in rat hearts.
Authors: M Akao, H Otani, M Horie, M Takano, A Kuniyasu, H Nakayama, I Kouchi, T Murakami, S Sasayama
Journal: Journal of Clinical Investigation (1997)

The cardiac ATP-sensitive potassium (KATP) channel is thought to be a complex composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the sulfonylurea receptor (SUR2). This channel is activated during myocardial ischemia and protects the heart from ischemic injury. We examined the transcriptional expression of these genes in rats with myocardial ischemia. 60 min of myocardial regional ischemia followed by 24-72 h, but not 3-6 h, of reperfusion specifically upregulated Kir6.1 mRNA not only in the ischemic (approximately 2.7-3.1-fold) but also in the nonischemic (approximately 2.0-2.6-fold) region of the left ventricle. 24 h of continuous ischemia without reperfusion also induced an increase in Kir6.1 mRNA in both regions, whereas 15-30 min of ischemia followed by 24 h of reperfusion did not induce such expression. In contrast, mRNAs for Kir6.2 and SUR2 remained unchanged under these ischemic procedures. Western blotting demonstrated similar increases in the Kir6.1 protein level both in the ischemic (2.4-fold) and the nonischemic (2.2-fold) region of rat hearts subjected to 60 min of ischemia followed by 24 h of reperfusion. Thus, prolonged myocardial ischemia rather than reperfusion induces delayed and differential regulation of cardiac KATP channel gene expression.
Effects of inspiratory flow waveforms on arterial blood gases and respiratory mechanics after open heart surgery
Authors: G Polese, P Lubli, R Poggi, A Luzzani, J Milic-Emili, A Rossi
Journal: European Respiratory Journal (1997)

The clinical usefulness of inspiratory flow pattern manipulation during mechanical ventilation remains unclear. The aim of this study was to investigate the effects of different inspiratory flow waveforms, i.e. constant, sinusoidal and decelerating, on arterial blood gases and respiratory mechanics, in mechanically ventilated patients. Eight patients recovering after open heart surgery for valvular replacement and/or coronary bypass were studied. The ventilator inspiratory flow waveform was changed according to a randomized sequence, keeping constant the other variables of the ventilator settings. We measured arterial blood gases, flow, volume and pressure at the proximal (airway opening pressure (Pao)) and distal (Ptr) ends of the endotracheal tubes before and after 30 min of mechanical ventilation with each inspiratory flow waveform. We computed breathing pattern, respiratory mechanics (pressures and dynamic elastance) and inspiratory work, which was then partitioned into its elastic and resistive components. We found that: 1) arterial oxygen tension (Pa,O2) and arterial carbon dioxide tension (Pa,CO2) were not affected by changes in the inspiratory flow waveform; and 2) peak Pao and Ptr were highest with sinusoidal inspiratory flow, whilst mean Pao and Ptr and total work of breathing were least with constant inspiratory flow, mainly because of a concomitant decrease in resistive work during constant flow inflation. The effects of the inspiratory flow profile on Pao, Ptr and total inspiratory work performed by the ventilator were mainly due to the resistive properties of the endotracheal tubes. We conclude that the ventilator inspiratory flow waveform can influence patients' respiratory mechanics, but has no impact on arterial oxygen and arterial carbon dioxide tension.
Primary Immunodeficiency Diseases
Authors: Jennifer M. Puck
Journal: JAMA (1997)

Primary immunodeficiencies are rare, but important for 3 reasons. First, a high index of suspicion and prompt diagnosis can lead to lifesaving treatment or significant improvement in quality of life. Second, appreciation of the genetic nature of a host defense defect makes possible family counseling and carrier and prenatal diagnosis. Finally, the large and growing list of human genetic defects in immune pathways provides an important tool for understanding human immunoregulation. Many inherited immunodeficiency diseases have had their genetic cause proven with the discovery of their disease genes within the past 5 years. These diseases provide a framework into which additional diseases and disease gene discoveries can be added as the rapid progress in molecular immunology and genetics continues.
P8 3D BIOLOGICAL SCAFFOLDS OBTAINED FROM DISCARDED HUMAN LIVERS AS A PLATFORM FOR TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Authors: G. Mazza, K. Rombouts, M. Malago', D. Dhar, A. Hall, P. Dhillon, M. Crawford, J. Godovac-Zimmermann, B. Fuller, B. Davidson, P. De Coppi, M. Pinzani
Journal: Journal of Hepatology (2014)
Long-term treatment of NZB mice with anti-CD4 results in wasting disease, lymphoid atrophy and chronic diarrhea
Authors: Geraldo Oliveira, John Holton, Peter Lydyard
Journal: Gut Microbes (2010)

In this paper, we have shown that long-term treatment of NZB mice with anti-CD4 antibody results in four major pathological effects: firstly the development of a severe wasting disease; secondly lymphoid atrophy of the thymus, spleen, mesenteric lymph node and Peyers patches (PP); thirdly, severe chronic ulcerative colitis and fourthly a neutrophilia with neutrophil infiltration in the spleen, liver and mesenteric lymph nodes. At the same time, mice subjected to anti-CD4 treatment showed a reduction in the microbial diversity in ileal walls and contents, as well as in colonic contents, together with overgrowth of E. coli in the intestinal lumen and wall. In addition, there was the appearance of large numbers of spiral shaped bacteria on the mucosal surface often associated with colonic ulceration.
Molecular basis for congenital deficiency of alpha 2-plasmin inhibitor. A frameshift mutation leading to elongation of the deduced amino acid sequence.
Authors: O Miura, S Hirosawa, A Kato, N Aoki
Journal: Journal of Clinical Investigation (1989)

The present study was designed to elucidate the molecular genetic basis of a familial deficiency of alpha 2-plasmin inhibitor (alpha 2PI). Southern blot hybridization analysis with human alpha 2PI cDNA and genomic DNA probes demonstrated no gross deletion or rearrangement of the gene. By sequencing all the coding exons and exon-intron boundaries of the gene of a homozygote, we identified a single cytidine nucleotide insertion in the exon coding for the carboxyl-terminal region. This frameshift mutation leads to an alteration and elongation of the carboxyl-terminal portion of the deduced amino acid sequence. Synthetic oligonucleotide probes confirmed this frameshift mutation in all the affected family members including both heterozygous parents. In a transient expression assay, the alpha 2PI level in the culture medium of the cells transfected with the mutated alpha 2PI expression vector was very low and only 4% of that of the cells transfected with the normal vector, although the transcript levels and the cellular contents of alpha 2PIs did not differ significantly. Elongation of amino acid sequence in the mutant alpha 2PI was confirmed by an analysis of alpha 2PI in a transient expression experiment. These data indicate that this mutation is the cause of alpha 2PI deficiency in this pedigree.
American countries face major health problems because of aging and obesity, report says
Authors: S. Arie
Journal: BMJ (2012)

The Americas region faces extraordinary challenges to its health systems as its population ages and puts on weight at an unprecedented pace, a new report from the Pan American Health Organization (PAHO) warns.

Some 39% of the population of the Americas is expected to be overweight or obese by 2015, and the number of people aged over 60 years is expected to double (to 200 million) between 2006 and 2020, says the organization’s five yearly report on the region, Health In the Americas 2012 .1

These trends are among the most striking to emerge from the comprehensive report on the combination of political, economic, …
Adeno-associated Viral (AAV) Serotype 5 Vector Mediated Gene Delivery of Endothelin-converting Enzyme Reduces Aβ Deposits in APP + PS1 Transgenic Mice
Authors: Niki C Carty, Kevin Nash, Daniel Lee, Mary Mercer, Paul E Gottschall, Craig Meyers, Nicholas Muzyczka, Marcia N Gordon, Dave Morgan
Journal: Molecular Therapy (2008)

Reduction of Aβ deposition is a major therapeutic strategy in Alzheimer's disease (AD). The concentration of Aβ in the brain is modulated not only by Aβ production but also by its degradation. One of the proteases involved in the degradation of Aβ peptides is endothelin-converting enzyme (ECE). In this study, we investigated the effects of an intracranial administration of a seroptype 5 recombinant adeno-associated viral vector (rAAV) containing the ECE-1 synthetic gene on amyloid deposition in amyloid precursor protein (APP) plus presenilin-1 (PS1) transgenic mice. The rAAV vector was injected unilaterally into the right anterior cortex and hippocampus of 6-month-old mice, while control mice received an AAV vector expressing green fluorescent protein (GFP). Immunohistochemical testing for the hemagglutinin (HA) tag appended to ECE revealed strong expression in areas surrounding the injection sites but minimal expression in the contralateral regions. Immunohistochemical tests showed that Aβ decreases in the anterior cortex and hippocampus in mice receiving the ECE synthetic gene. Further, decreases in Congo red positive deposits were also observed in both regions. These results indicate that increasing the expression of β-amyloid degrading enzymes through gene therapy is a promising approach to the treatment of AD.
Bush says he will veto stem cell funding, despite vote in favour in Congress
Authors: Jeanne Lenzer
Journal: BMJ (2007)

The US Congress passed a controversial bill last week to allow federal funding of research that uses embryonic stem cells.

However, George Bush issued a statement immediately after the bill was passed saying that he will veto the bill on his return from the G8 summit in Germany. “If this bill were to become law,” said President Bush, “American taxpayers would for the first time in our history be compelled to support the deliberate destruction of human embryos.”

Although the bill was passed by a wide margin, it did not meet the two thirds majority needed to override any veto. Nevertheless, politicians who favour stem cell research are hoping to rally enough votes to override the anticipated presidential veto.

Pro-life advocates oppose …
Selection of antigen-specific, idiotype-positive B cells in transgenic mice expressing a rearranged M167-mu heavy chain gene.
Authors: J J Kenny, C O'Connell, D G Sieckmann, R T Fischer, D L Longo
Journal: The Journal of Experimental Medicine (1991)

Flow cytometric analysis of antigen-specific, idiotype-positive (id+), B cell development in transgenic mice expressing a rearranged M167-mu gene shows that large numbers of phosphocholine (PC)-specific, M167-id+ B cells develop in the spleen and bone marrow of these mice. Random rearrangement of endogenous V kappa genes, in the absence of a subsequent receptor-driven selection, should give rise to equal numbers of T15- and M167-id+ B cells. The observed 100-500-fold amplification of M167-id+ B cells expressing an endogenous encoded V kappa 24]kappa 5 light chain in association with the M167 VH1-id transgene product appears to be an antigen driven, receptor-mediated process, since no amplification of non-PC-binding M167 VH1/V kappa 22, T15-id+ B cells occurs in these mu-only transgenic mice. The selection and amplification of antigen-specific, M167-id+ B cells requires surface expression of the mu transgene product; thus, no enhancement of M167-id+ B cells occurs in the M167 mu delta mem-transgenic mice, which cannot insert the mu transgene product into the B cell membrane. Surprisingly, no selection of PC-specific B cells occurs in M167-kappa-transgenic mice although large numbers of B cells expressing a crossreactive M167-id are present in the spleen and bone marrow of these mice. The failure to develop detectable numbers of M167-id+, PC-specific B cells in M167-kappa-transgenic mice may be due to a very low frequency of M167-VH-region formation during endogenous rearrangement of VH1 to D-JH segments. The somatic generation of the M167 version of a rearranged VH1 gene may occur in less than one of every 10(5) bone marrow B cells, and a 500-fold amplification of this M167-Id+ B cell would not be detectable by flow cytometry even though the anti-PC antibody produced by these B cells is detectable in the serum of M167-kappa-transgenic mice after immunization with PC.
Case Mix in End-Stage Renal Disease
Authors: Alonzo L. Plough, Susanne R. Salem, Michael Shwartz, John M. Weller, C. William Ferguson
Journal: New England Journal of Medicine (1984)

This study examines the mix of cases in facilities for the treatment of end-stage renal disease in Michigan during the period January 1973 through September 1981. We compared 3135 patients treated in 29 hospital-based facilities with 307 patients treated in five proprietary, free-standing facilities. Patients were assigned to one of five severity groups on the basis of age, race, primary renal diagnosis, and accompanying conditions. The five severity groups were differentiated by the probability of death in the first year of treatment and the risk of death over the course of treatment. We then compared the distribution of patients in the five severity groups in hospital-based facilities with that in free-standing facilities. Hospital-based facilities had a higher percentage of patients in the higher-severity groups. When severity was measured by one-year survival, the difference was statistically significant. Sixty per cent of hospital-based patients were in the three highest severity groups, as compared with 50 per cent of patients in free-standing facilities. Within each severity group, hospital-based patients had a lower five-year survival rate than patients in free-standing facilities. Our findings suggest that the case mix in hospital-based facilities may include more severe cases than that in proprietary, free-standing facilities, but more data from more facilities will be needed before firm conclusions can be drawn. If the cost of providing services is related to case-mix severity, such data could have implications for federal reimbursement policies.
Reactivity of primary biliary cirrhosis sera with a human fetal liver cDNA clone of branched-chain α-keto acid dehydrogenase dihydrolipoamide acyltransferase, the 52 kD mitochondrial autoantigen
Authors: Charles D. Surh, Dean J. Danner, Aftab Ahmed, Ross L. Coppel, Ian R. Mackay, E. Rolland Dickson, M. Eric Gershwin
Journal: Hepatology (1989)

Antimitochondrial autoantibodies recognizing 68 to 74 and 50 to 52 kD inner membrane mitochondrial antigens are characteristically present in sera of patients with primary biliary cirrhosis. The biochemical identification of the antigens, however, has remained elusive. We report herein that the 52 kD antigen is the dihydrolipoamide acyltransferase of the branched-chain α-keto acid dehydrogenase complex. This was demonstrated by three experiments through the use of recombinant fusion protein expressed in Escherichia coli from a cDNA insert encoding the human autoantigen. First, 36 of 37 primary biliary cirrhosis patients exhibiting reactivity toward the 50 to 52 kD mitochondrial antigen by immunoblotting also showed reactivity toward the recombinant fusion protein. Second, absorption of primary biliary cirrhosis sera with recombinant fusion protein, but not with an irrelevant recombinant clone, the F-specific rat liver antigen, was effective in absorbing out reactivity against the 50 to 52 kD mitochondrial antigen but not the 68 to 74 kD antigen. Third, complete removal of reactivity toward all four different isoelectric point polypeptides at 50 to 52 kD was observed in two-dimensional gel analysis. Furthermore, primary biliary cirrhosis sera were analyzed with mitochondria from three sources, rat liver, human placenta and bovine heart, in order to compare reactivity patterns and to determine precisely the comparative molecular weights of the autoantigens in the three species. The availability of recombinant autoantigens will provide improved diagnostic tests and, more importantly, will allow definite issues in primary biliary cirrhosis to be studied, including identification of immunodominant epitopes, the significance of autoantigen recognition and the establishment of autoreactive T cell clones.
Hypersplenic Thrombocytopenia Differentiated from Increased Peripheral Destruction by Platelet Volume
Authors: SIMON KARPATKIN
Journal: Annals of Internal Medicine (1978)

Platelet volume distribution was examined in 16 patients with hepatosplenomegaly and platelet counts of 45 000 to 90 000/mm3; 12 patients with autoimmune thrombocytopenia and randomly matched platelet counts; and 20 normal subjects. Five platelet volume variables of increasing platelet size were defined from the averages of 20 normal curves. Patients with hypersplenism had decreased volume values of 78% to 87% (mean, 83%) of the average normal population (P < 0.001). Patients with autoimmune thrombocytopenic purpura had values significantly greater than normal by 124% to 149% (mean, 134%) (P < 0.001). Patients with autoimmune thrombocytopenic purpura, when compared with hypersplenic patients, had significantly greater platelet volume values ranging from 154% to 174% (mean, 161%), P < 0.001. We concluded that patients with hepatosplenomegaly have smaller platelets in their peripheral blood and a platelet volume distribution that can be distinguished easily from patients with autoimmune thrombocytopenic purpura, despite comparable platelet counts.
Psychological Bases of War
Authors: Marshall F. Gilula
Journal: JAMA (1974)

Behavioral scientists have grasped at many explanations for man's warring nature. Man's ability to rationalize any behavior is at best a weak justification. Many causes of war have been suggested: contiguity, habituation, social learning, predation, psychological defenses (eg, rationalization, blaming, denial, projection), the host of fears associated with the human condition, territoriality and power, intolerable frustration, biologically rooted aggressive instincts, and sadism. As a polished book, these conference proceedings between American and Israeli psychoanalysts represent another rationalization that illuminates yet hardly justifies the continuing existence of war. Obviously, interesting material includes thoughts of many participants who had recently lived with war. The chief weakness of applying psychoanalytic thought to social problems such as war lies in moving from individual pathology and its solutions to the group situation. War is not a "proper" object for psychoanalytic study. Conference participants demonstrate one reason for this that making war is an activity of
Former staff at <i>CMAJ</i> launch open access journal
Authors: David Spurgeon
Journal: BMJ (2007)

Canada's first paperless, open access, online medical journal was launched last week (www.openmedicine.ca). Its origins lie in a dispute about editorial independence that led to the firing of senior editors at CMAJ , the journal of the Canadian Medical Association, and the resignation of most of its editorial board ( BMJ 2006;332:687, doi: 10.1136/bmj.332.7543.687-a).

The new journal's mission is “to facilitate the equitable global dissemination of high-quality health research; to promote international dialogue and collaboration on health issues; to improve clinical practice; and to deepen the understanding of health and health care.” It is not for profit, editorially independent, and will not charge subscription fees or run advertisements for drugs or medical devices.

Six of the editorial team at Open Medicine were formerly editors at CMAJ and left after the dispute. Ten editorial board members at …
The kangaroo as a model for the study of hypertrophic cardiomyopathy in man
Authors: M F O'ROURKE, A P AVOLIO, W W NICHOLS
Journal: Cardiovascular Research (1986)

In experiments in 14 anaesthetised kangaroos, 10 developed unexpected ventricular fibrillation and died. In seeking a cause for this, similarities were noted with hypertrophic cardiomyopathy (HC) in man. Like patients with this condition, kangaroos have unexplained left ventricular hypertrophy and are known to be susceptible to sudden death with excitement and exertion. Retrospective analysis of all data showed other features of hypertrophic cardiomyopathy: unusually rapid left ventricular pressure development in systole (peak dP/dt: kangaroo 3602 (SEM472); HC 1947(SEM172) mmHg X s-1), unusually slow left ventricular relaxation (exponential time constant: kangaroo 54(SEM7); HC 63 (SEM5) ms; relaxation time: kangaroo 128(SEM7); HC 112(SEM7) ms), and inappropriately long duration of mechanical systole in relation to ventricular depolarisation (393(SEM21) ms and 214(SEM15) ms respectively). A disparity between the duration of mechanical systole and electrical activation caused a type of incomplete tetanus to develop with ventricular extrasystoles, a phenomenon previously seen in patients with hypertrophic cardiomyopathy. These findings suggest that the kangaroo may be a useful experimental model for studying the fatal rhythm disturbances and abnormal ventricular dynamics in human hypertrophic cardiomyopathy.