tbuckley/cabot-search huggingface dataset:
Galactosamine-induced fulminant hepatic necrosis in unanesthetized canines
Authors: J A Diaz-Buxo, S Blumenthal, D Hayes, P Gores, B Gordon
Journal: Hepatology (1997)

A large animal model of fulminant hepatic necrosis is necessary to test the efficacy of artificial liver support systems. A recent model was developed using D-galactosamine in anesthetized dogs. Because of the difficulties encountered with prolonged anesthesia, a similar protocol was used in 10 unanesthetized dogs. Intravenous infusions of D-galactosamine (1.0 to 1.5 gm/kg) did not result in uniform death of all animals at 72 hours or development of hypoglycemia. Severe hepatic necrosis was observed in all animals, but residual hepatocyte viability was evident in some. All animals developed severe consumption coagulopathy with histological evidence of disseminated intravascular coagulation (DIC) in four. A clinical picture characteristic of endotoxic shock was observed in most animals as a terminal event. The presence of endotoxin was confirmed in all dogs tested after 12 hours (7/10). The differences observed between this model and the anesthetized model are probably because of the toxic synergism between halothane and D-galactosamine. Neither model seems satisfactory for the testing of artificial liver support systems. The halothane model requires extremely long periods of anesthesia and mechanical ventilation. The present model does not cause uniform or universal death of the animals within 3 days. Foremost, both models result in DIC and endotoxic shock, neither of which is likely to respond to bioartificial liver support or treatment with conventional dialysis membranes.
Metabolomics Applied to Exhaled Breath Condensate in Childhood Asthma
Authors: Silvia Carraro, Serge Rezzi, Fabiano Reniero, Károly Héberger, Giuseppe Giordano, Stefania Zanconato, Claude Guillou, Eugenio Baraldi
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Metabolomic analysis provides biochemical profiles of low-molecular-weight endogenous metabolites in biological fluids.Objectives: The aim of this study was to assess the feasibility of nuclear magnetic resonance (NMR)–based metabolomic analysis applied to exhaled breath condensate (“breathomics”). Information coming from NMR spectra was analyzed with a view to establish the NMR variables that best discriminate between children with asthma and healthy children.Methods: Twenty-five children with asthma (17 with persistent asthma treated with inhaled corticosteroids, 8 with intermittent asthma inhaled corticosteroid naive; age, 7–15 yr) and 11 healthy age-matched control subjects were enrolled. Every child performed exhaled nitric oxide measurement, spirometry, and condensate collection. Condensate samples were analyzed by means of NMR spectroscopy. Linear and partial least squares discriminant analyses were applied to data obtained from the NMR spectra.Measurements and Main Results: The combination of exhaled nitric oxide and FEV1 discriminates children with asthma and healthy children with a success rate of approximately 81%, whereas selected signals from NMR spectra offer a slightly better discrimination (∼ 86%). The selected NMR variables derive from the region of 3.2 to 3.4 ppm, indicative of oxidized compounds, and from the region of 1.7 to 2.2 ppm, indicative of acetylated compounds.Conclusions: Metabolomics can be applied to exhaled breath condensate, leading to the characterization of airway biochemical fingerprints. The presence of acetylated compounds suggests new metabolic pathways that may have a role in asthma pathophysiology.
The effects of suramin on human adrenocortical cells in vitro: Suramin inhibits cortisol secretion and adrenocortical cell growth
Authors: K. Dorfinger, H. Vierhapper, A. Wilfing, S. Czernin, B. Niederle, P. Nowotny, M. Peterlik, W. Waldhäust, B. Grubeck-Loebenstein
Journal: Metabolism (1991)
Efficient Peripheral Clonal Elimination of B Lymphocytes in MRL/<i>lpr</i> Mice Bearing Autoantibody Transgenes
Authors: Jennifer A. Kench, David M. Russell, David Nemazee
Journal: The Journal of Experimental Medicine (1998)

Peripheral B cell tolerance was studied in mice of the autoimmune-prone, Fas-deficient MRL/ lpr.H-2d genetic background by introducing a transgene that directs expression of membrane-bound H-2Kb antigen to liver and kidney (MT-Kb) and a second transgene encoding antibody reactive with this antigen (3-83μδ, anti-Kk,b). Control immunoglobulin transgenic (Ig-Tg) MRL/lpr.H-2d mice lacking the Kb antigen had large numbers of splenic and lymph node B cells bearing the transgene-encoded specificity, whereas B cells of the double transgenic (Dbl-Tg) MRL/lpr.H-2d mice were deleted as efficiently as in Dbl-Tg mice of a nonautoimmune B10.D2 genetic background. In spite of the severely restricted peripheral B cell repertoire of the Ig-Tg MRL/lpr.H-2d mice, and notwithstanding deletion of the autospecific B cell population in the Dbl-Tg MRL/lpr.H-2d mice, both types of mice developed lymphoproliferation and exhibited elevated levels of IgG anti-chromatin autoantibodies. Interestingly, Dbl-Tg MRL/lpr.H-2d mice had a shorter lifespan than Ig-Tg MRL/lpr.H-2d mice, apparently as an indirect result of their relative B cell lymphopenia. These data suggest that in MRL/lpr mice peripheral B cell tolerance is not globally defective, but that certain B cells with receptors specific for nuclear antigens are regulated differently than are cells reactive to membrane autoantigens.
Anatomy and physiology for students of physiotherapy, occupational therapy and gymnastics.
Authors: Lester S. King
Journal: JAMA (1963)

<b>Human anatomy and physiology</b>. By Barry G. King and Mary Jane Showers. 5th ed. 469 p. $6. W. B. Saunders Co., W Washington Sq, Philadelphia 5, 1963 <b>Dynamic anatomy and physiology</b>. By L. L. Langley et al. 2nd ed. 802 p. $7.95. Blakiston Division, McGraw-Hill Book Co., 330 W 42nd St, New York 36, 1963 There are many groups which require texts on human anatomy and physiology discussed at a level lower than that demanded at medical schools. The almost simultaneous appearance of three separate volumes in this area, one representing a second edition, one a fourth edition, and one a fifth edition, illustrates the great demand. These books indicate how important it is that an author keep in mind the audience to which he is directing his efforts. Correlatively, a book can be evaluated only in reference to the audience for which it is designed. Smout and McDowall have
PROGNOSIS OF HYPERTHYROIDISM TREATED BY ANTITHYROID DRUGS
Authors: David H. Solomon
Journal: JAMA (1953)

Hyperthyroidism can regularly be controlled by the administration of antithyroid drugs, and a euthyroid or hypothyroid state can be maintained for as long as treatment is continued. The optimal therapeutic schedules and the expected sequence of events during treatment have been determined.<sup>1</sup>There remains, however, considerable divergence of opinion on the incidence of prolonged remission after cessation of a course of therapy with an antithyroid compound.<sup>2</sup>This may in part be attributed to the many reports based on observation of patients for only a short time after the conclusion of treatment. Where this objection does not apply, the published rates of remission are nonetheless difficult to interpret, since they have been determined by giving equal weight to patients with a wide range of post-therapeutic periods of observation. This procedure introduces an obvious source of error into the data and also makes it impossible to derive the incidence of
Patients with RA in remission on TNF blockers: when and in whom can TNF blocker therapy be stopped?
Authors: B. Saleem, H. Keen, V. Goeb, R. Parmar, S. Nizam, E. M. A. Hensor, S. M. Churchman, M. Quinn, R. Wakefield, P. G. Conaghan, F. Ponchel, P. Emery
Journal: Annals of the Rheumatic Diseases (2010)

Combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockade has increased remission rates in patients with rheumatoid arthritis. However, there are no guidelines regarding cessation of therapy. There is a need for markers predictive of sustained remission following cessation of TNF blocker therapy.Patients in remission (DAS28 <2.6) treated with a TNF blocker and MTX as initial or delayed therapy were recruited. Joints were assessed for grey scale synovitis and power Doppler (PD) activity. Immunological assessment involved advanced six-colour flow cytometry.Of the 47 patients recruited, 27 had received initial treatment and 20 delayed treatment with TNF blocking drugs. Two years after stopping TNF blocker therapy, the main predictor of successful cessation was timing of treatment; 59% of patients in the initial treatment group sustained remission compared with 15% in the delayed treatment group (p=0.003). Within the initial treatment group, secondary analysis showed that the only clinical predictor of successful cessation of treatment was shorter symptom duration before receiving treatment (median 5.5 months vs 9 months; p=0.008). No other clinical features were associated with successful cessation of therapy. Thirty-five per cent of patients had low PD activity but levels were not informative. Several immunological parameters were significantly associated with sustained remission including abnormal differentiation subset of T cells and regulatory T cells. Similar non-significant trends were observed in the delayed treatment group.In patients in remission with low levels of imaging synovitis receiving combination treatment with a TNF blocker and MTX, immunological parameters and short duration of untreated symptoms were associated with successful cessation of TNF blocker therapy.
The practice of ultraviolet phototherapy in the United Kingdom
Authors: G. DOOTSON, P.G. NORRIS, C.J. GIBSON, B.L. DIFFEY
Journal: British Journal of Dermatology (1994)

A survey, using a postal questionnaire, was carried out to examine the current practice of UVB phototherapy in dermatology centres in the U.K. The questionnaire was sent to 115 dermatology departments, and sought information regarding the type and age of each machine used for ultraviolet B (UVB) phototherapy, methods of prescribing, recording and terminating patient exposure, and the skin conditions treated. Completed questionnaires were received from 87 of the 115 centres, giving a response rate of 76%. The survey showed that an appreciable number of U.K. phototherapy centres are using equipment which is both old, and suboptimal in producing a therapeutic response. There appeared to be a wide variation in the approach to phototherapy, both in terms of prescribing initial and incremental exposure, and in terminating treatment. The findings suggest that effectiveness and efficiency might be improved, and the risk/benefit ratio of phototherapy further reduced, by some rationalization of treatment protocols.
Serial computed tomography scanning in acute pancreatitis: a prospective study.
Authors: N J London, J P Neoptolemos, J Lavelle, I Bailey, D James
Journal: Gut (1989)

One hundred and two patients with acute pancreatitis had abdominal computed tomography (CT) scans within 72 hours of admission, at one week and at six weeks. Twenty eight attacks were clinically severe, 74 clinically mild. Ninety three (91%) admission scans, 85 (84%) one week scans, and 52 (51%) six week scans were abnormal. The aetiology of the pancreatitis could be inferred from 28 (27%) of admission scans, the CT sign of fatty liver having a sensitivity of 21% and specificity of 100% for alcoholic aetiology. The sensitivity of CT for gall stone aetiology was 34%, specificity 100%. The pancreatic size indices (max anteroposterior measurement of head x max anteroposterior measurement of body) of those patients with severe attacks were significantly greater than those with mild attacks on admission, at one week and at six weeks (p less than 0.004). Fourteen pseudocysts were detected by CT, five (36%) of which were clinically apparent. The pseudocyst size indices (max anteroposterior x max transverse measurement) of the pseudocysts which were clinically apparent were significantly greater than those which were not apparent (p less than 0.01) and only those pseudocysts with a size index greater than or equal to 15 cm2 required treatment.
Tobacco-addiction-death link shown but labels don't tell it
Authors: M. F. Goldsmith
Journal: JAMA (1986)

The enthusiasm for the positive results of antismoking campaigns since 1964 in the US needs to be tempered with concern about the future impact of cigarettes on the populations of less developed nations according to Dr. William B. Foege the former director of the Centers for Disease Control (CDC) in Atlanta and currently special assistant for policy development at CDC.  Foege cites the role that declining smoking rates may have played in the documented decrease in fatal heart attacks reported at the 1985 American Public Health Association meeting and the leveling off of rates of lung cancer in men -- but not in women -- in this country.  In the US there are marked changes and smoking is now becoming a lower-class habit.  Also tobacco use is increasing in the poorest nations.  William U. Chandler in the publication Banishing Tobacco writes that antismoking efforts achieve only limited success in industrial nations and are failing in developing countries.  Chandler advocates a strategy of banishing tobacco by means of informational campaigns and a ban on smoking in the workplace restaurants and public buildings.  In only 4 countries -- Great Britain Norway Zambia and Zimbabwe -- are fewer cigarettes smoked than in 1964 according to Chandler.  He agrees with Foeges contention that smoking prevalence has gone down in the US (from 43% to 32%) but points out that persons who do smoke cigarettes now smoke more heavily than they used to.  According to the Worldwatch study Greece leads the world in cigarette use per capita followed closely by Japan and the US.  Hungary and Poland also rank high on the list.  Worldwide tobacco consumption has gone up 75% in the last 2 decades and Chandler warns that lung cancer from smoking will increase 50% worldwide by the end of the century unless stronger measures are taken to control tobacco use.  He claims that no country is taking action against tobacco commensurate with its cost in human lives.  Some antismoking activists have advocated directing specific economic sanctions against cigarette manufacturers.  This seems reasonable but organized boycotts are illegal and due to the widespread diversification of the tobacco industry they would have little or no effect on the companies overall profit picture.  Foege proposes that the health professions support the idea of a time-limited subsidy for small tobacco farmers to help them convert to other crops if they want to do so.
Expression and characterization of a truncated murine Fc gamma receptor.
Authors: Z X Qu, J Odin, J D Glass, J C Unkeless
Journal: The Journal of Experimental Medicine (1988)

We have isolated a recombinant secreted Fc gamma R beta molecule by deletion of the transmembrane and cytoplasmic domains encoding sequence from a Fc gamma R beta 1 cDNA clone, and insertion of the truncated cDNA into a eukaryotic expression vector, pcEXV-3. To express and amplify the production of the truncated Fc gamma R beta molecule, we transfected the truncated cDNA plasmid into a dihydrofolate reductase-minus CHO cell line along with a dhfr minigene, and amplified the gene products with methotrexate. The resulting cell line secretes 2-3 micrograms/ml/24 h of truncated Fc gamma R beta, which can be readily purified by affinity chromatography on IgG-Sepharose. The truncated Fc gamma R beta has a Mr of 31-33,000 on SDS-PAGE and is glycosylated. N-glycosidase F cleavage reduces the Mr to 19,000, consistent with the size of the truncated product, 176 amino acid residues. There are two disulfide bonds in the protein. Binding of immune complexes formed between DNP20BSA and anti-DNP mAbs reveals better binding of IgG1 aggregates than that of IgG2b and IgG2a aggregates. The binding of the immune complexes was somewhat better at more acidic pH, in contrast to previous experiments with binding of purified Fc gamma R to immune complex-coated beads. We were surprised to observe that the truncated Fc gamma R beta did not react with the anti-Fc gamma R mAb 6B7C. Previous work had shown that 6B7C reacts with Fc gamma R on immunoblots, fails to bind to the surface of resting B cells and peritoneal macrophages, but does bind to macrophage cell lines and LPS-stimulated B cells. We show, by binding of mAb 6B7C to a peptide conjugate, that the 6B7C epitope lies within residues 169-183 of the intact Fc gamma R beta, which is just outside the plasma membrane. The availability of the truncated Fc gamma R beta in microgram quantities should facilitate further analysis of structure and function of these receptors.
P17.20 * PATTERNS OF CARE AND OUTCOME FOR PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: L. De Cock, Q. Sala, M. Barrie, C. Boucard, P. Metellus, E. Tabouret, L. Padovani, D. Figarella-Branger, H. Dufour, O. Chinot
Journal: Neuro-Oncology (2014)

BACKGROUND: Access to salvage treatment for patients with recurrent GB is poorly documented in daily practice. Our objective was to assess patterns of care and outcome in patients with recurrent GB. METHODS: A retrospective analysis of consecutive patients with histologically proven GB treated in 2008 and 2011 at Timone University Hospital was performed. Clinical, therapeutic and outcome data were collected. RESULTS: 207 patients were identified (2008: n = 99; 2011: n = 108). Patient's characteristics, pattern of care and outcome were similar between 2008 and 2011 and, therefore analyzed together. Overall survival from initial diagnosis (OSI) was 15.0 months (95% CI 12.9-17.1). Recurrence was diagnosed in 158 pts (76.3%). Overall survival from recurrence (OSR) was 6.6 months (95% CI 5.6-7.5). 117/158 pts (74%) of them received salvage treatment; 41 (26%) received no trt. 53, 48, and 16 pts received 1, 2 and > 2 lines at recurrence respectively. 2line treatment consist of chemotherapy (CT), n = 23 (19.7%), bevacizumab (BEV) +/- CT, n = 63 (53.8%), surgery +/- carmustine wafer (CW), n = 16 (10.1%), reirradiation (RRT) (1) and inclusion in clinical trials, n = 16 (9.5%). OSR in patient treated with CT + /-BEV was 8.0 months (95% CI 6.9-9.1) and OSI was 18.9 months (95% CI 16.3-21.5). OSR in patients with local treatment (surgery +/-CW, RRT) was 10.8 months (95% CI 7.7-13.8); OSI was 29.7 months (CI 95% 10.5-39). In pts who received no salvage trt, OSR and OSI were 1.8 (95% CI 1.4-2.1) and 7.5 (95% CI 6.4-8.6) months respectively. In patients aged over 70 years (n = 76), recurrence was determined in 50 of whom 30 (60%) received a salvage treatment. OSR was 5.2 months (95% CI 3.9-6.6) and OSI was 8.9 months (95% CI 7.5-10.4). In pts aged ≤70 years (n = 131), recurrence was determined in 108 of whom 87 (81%) received a treatment at progression. OSR was 7.1 months (95% CI 5.9-8.4) and OSI was 18.1 months (95% CI 15.2-21.0). CONCLUSION: In a center assuming mainly primary care of patients, 75% of the pts identified with recurrent GB received salvage treatment. Differences in outcome associated to systemic treatment, second surgery, and no treatment could be related to pts/tumor heterogeneity and treatment. Access to and results of salvage treatment in elderly are limited.
Primary myelofibrosis: 2014 update on diagnosis, risk‐stratification, and management
Authors: Ayalew Tefferi
Journal: American Journal of Hematology (2014)

Disease overview : Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell‐derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival. Diagnosis : Diagnosis is based on bone marrow morphology. The presence of JAK2 , CALR , or MPL mutation is supportive but not essential for diagnosis; approximately 90% of patients carry one of these mutations and 10% are “triple‐negative.” None of these mutations are specific to PMF and are also seen in essential thrombocythemia (ET). Prefibrotic PMF mimics ET in its presentation and the distinction, enabled by careful bone marrow morphological examination, is prognostically relevant. Differential diagnosis also includes chronic myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. Risk Stratification : The Dynamic International Prognostic Scoring System‐plus (DIPSS‐plus) uses eight predictors of inferior survival: age &gt;65 years, hemoglobin &lt;10 g/dL, leukocytes &gt;25 × 10 9 /L, circulating blasts ≥1%, constitutional symptoms, red cell transfusion dependency, platelet count &lt;100 × 10 9 /L, and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, −7/7q−, i(17q), inv(3), −5/5q−, 12p−, or 11q23 rearrangement). The presence of 0, 1, “2 or 3,” and ≥4 adverse factors defines low, intermediate‐1, intermediate‐2, and high‐risk disease with median survivals of approximately 15.4, 6.5, 2.9, and 1.3 years, respectively. High risk disease is also defined by CALR − / ASXL1 + mutational status. Risk‐Adapted Therapy : Observation alone is adequate for asymptomatic low/intermediate‐1 risk disease, especially with CALR + / ASXL1 − mutational status. Stem cell transplant is considered for DIPSS‐plus high risk disease or any risk disease with CALR − / ASXL1 + mutational status. Investigational drug therapy is reasonable for symptomatic intermediate‐1 or intermediate‐2 risk disease. Splenectomy is considered for drug‐refractory splenomegaly. Involved field radiotherapy is most useful for post‐splenectomy hepatomegaly, non‐hepatosplenic EMH, PMF‐associated pulmonary hypertension, and extremity bone pain. Am. J. Hematol. 89:916–925, 2014. © 2014 Wiley Periodicals, Inc.
Mast cells in the brain: evidence and functional significance
Authors: Rae Silver, Ann-Judith Silverman, Ljubiša Vitković, Israel I Lederhendler
Journal: Trends in Neurosciences (1996)

For the past two decades the brain has been considered to be an immune-privileged site that excludes circulating cells from the parenchyma. New evidence indicates that some hematocytes reside in the brain, while others traffic through it. Mast cells belong to both of these functional types. Moreover, the appearance of mast cells in the CNS can be triggered behaviorally. After a brief period of courtship, for example, there is a marked increase in mast cells in the medial habenula of sexually active doves compared with controls. Exposure to gonadal steroids that occur endogenously or that are administered exogenously increases both the number of mast cells and their state of activation in the brain. These results show that hematopoietic cells can provide targeted delivery of neuromodulators to specific regions of the brain, thereby influencing neural-endocrine interactions. Trends Neurosci. (1996) 19, 25–31
The Judicial Council.
Authors: John B. Roberts
Journal: JAMA (1895)

Philadelphia, April 10, 1895. <h3>To the Editor:</h3> —TheJournalof the 6th inst. contains a criticism of the circular, relative to advertisements, recently sent to all members of theAmerican Medical Associationby the Philadelphia County Medical Society. In the criticism occurs a personal allusion which impels me to request the publication of this letter. TheJournalsays: "There are two direct mis-statements in the committee's report which we are sure they will be glad to have corrected; one is that the decision of the Judicial Council was not given to them or published. We notice that Dr. John B. Roberts has signed this document, and that he was also Secretary of the Judicial Council. If he failed to notify his associates on the committee of the action of the Council surely theJournalis not to blame." It is true that I was a delegate of the Philadelphia County