tbuckley/cabot-search huggingface dataset:
Rituximab and Subcutaneous 2-Chloro-2′-Deoxyadenosine Combination Treatment for Patients With Waldenström Macroglobulinemia: Clinical and Biologic Results of a Phase II Multicenter Study
Authors: Daniele Laszlo, Giovanna Andreola, Luigi Rigacci, Alberto Fabbri, Cristina Rabascio, Patrizia Mancuso, Giancarlo Pruneri, Davide Radice, Antonello Pinto, Ferdinando Frigeri, Liliana Calabrese, Atto Billio, Francesco Bertolini, Giovanni Martinelli
Journal: Journal of Clinical Oncology (2010)

Purpose To assess the efficacy of 2-chloro-2′-deoxyadenosine (2-CdA) given subcutaneously (SC) in combination with rituximab in the treatment of newly diagnosed/pretreated patients with Waldenström macroglobulinemia (WM) and to correlate the response to treatment with biologic findings (immunophenotypic and pharmacogenomic analysis). Patients and Methods From December 2003 to February 2007, 29 patients were enrolled. Intended therapy consisted of a combination of rituximab (375 mg/m 2 ) on day 1 followed by 2-CdA 0.1 mg/kg (SC injection) for 5 consecutive days, administered monthly for four cycles. Anemia (n = 16), neurologic symptoms (n = 6), symptomatic cryoglobulinemia (n = 4), and thrombocytopenia (n = 3) represented the reasons for starting treatment. The expression of ζ chain–associated protein kinase 70 (Zap-70) and of seven genes involved in 2-CdA metabolism as markers of response to the combination treatment was evaluated. Results With a median follow-up of 43 months, the overall response rate observed was 89.6%, with seven complete responses (CR), 16 partial responses, and three minor response, without any difference between newly or pretreated patients (P = .522). The therapy was well tolerated, except for transitory cardiac toxicity (n = 2) and intolerance to rituximab (n = 2). No major infections were observed despite the lack of antimicrobial prophylaxis. No patients developed transformation to high-grade non-Hodgkin's lymphoma nor myelodysplasia. Low expression levels of human concentrative nucleoside transporter 1 (hCNT1) were correlated with the failure to achieve a CR (P = .024), whereas no association with Zap-70 expression was found. Conclusion The combination of rituximab and SC 2-CdA is safe and effective in patients with WM requiring treatment. The pharmacogenomic analysis associated with the study suggests hCNT1 might be beneficial in predicting clinical response to such a combination treatment.
An office-place stepping device to promote workplace physical activity
Authors: David A McAlpine, Chinmay U Manohar, Shelly K McCrady, Donald Hensrud, James A Levine
Journal: British Journal of Sports Medicine (2007)

Objective: It was proposed that an office-place stepping device is associated with significant and substantial increases in energy expenditure compared to sitting energy expenditure. The objective was to assess the effect of using an office-place stepping device on the energy expenditure of lean and obese office workers. Methods: The office-place stepping device is an inexpensive, near-silent, low-impact device that can be housed under a standard desk and plugged into an office PC for self-monitoring. Energy expenditure was measured in lean and obese subjects using the stepping device and during rest, sitting and walking. 19 subjects (27±9 years, 85±23 kg): 9 lean (BMI&lt;25 kg/m 2 ) and 10 obese (BMI&gt;29 kg/m 2 ) attended the experimental office facility. Energy expenditure was measured at rest, while seated in an office chair, standing, walking on a treadmill and while using the office-place stepping device. Results: The office-place stepping device was associated with an increase in energy expenditure above sitting in an office chair by 289±102 kcal/hour (p&lt;0.001). The increase in energy expenditure was greater for obese (335±99 kcal/hour) than for lean subjects (235±80 kcal/hour; p = 0.03). The increments in energy expenditure were similar to exercise-style walking. Conclusion: The office-place stepping device could be an approach for office workers to increase their energy expenditure. If the stepping device was used to replace sitting by 2 hours per day and if other components of energy balance were constant, weight loss of 20 kg/year could occur.
Thoracic Radiation Therapy Alone Compared with Combined Chemoradiotherapy for Locally Unresectable Non-Small Cell Lung Cancer
Authors: Roscoe F. Morton, James R. Jett, William L. McGinnis, John D. Earle, Terry M. Therneau, James E. Krook, Thomas E. Elliott, James A. Mailliard, Robert A. Nelimark, Andrew W. Maksymiuk, Ronald G. Drummond, John A. Laurie, John W. Kugler, Richard T. Anderson
Journal: Annals of Internal Medicine (1991)

▪ Objective: To compare the survival of patients with medically inoperable or unresectable stage III non-small cell lung cancer treated with thoracic radiotherapy alone or in combination with chemotherapy. ▪ Design: Randomized, prospective phase III trial. ▪ Setting: Multi-institutional cooperative oncology group. ▪ Patients: A total of 121 patients were enrolled in the study, of whom 7 (5.8%) were ineligible. All patients were ambulatory and had measurable or evaluable disease. Before they were randomized, patients were stratified by ECOG performance score, histologic type, maximum tumor diameter, and NCCTG institution. ▪ Interventions: Radiotherapy consisted of a total of 5000 cGy in 5 weeks with a 1000 cGy boost in 5 fractions to a small tumor field. Combined modality therapy was MACC which is intravenous methotrexate, intravenous doxorubicin, intravenous cyclophosphamide, and oral lomustine (CCNU), on day 1 and 28. Chemotherapy was followed by identical thoracic radiotherapy 4 weeks after the second cycle of chemotherapy. Four weeks after thoracic radiotherapy was completed, patients received another two cycles of identical chemotherapy. Patients who had progression of disease after chest irradiation only were treated with MACC chemotherapy. ▪ Main Results: Major clinical responses were observed in 31 of 56 (55%; 95% Cl, 42% to 68%) patients treated with combination therapy and 37 of 58 (64%; Cl, 51 % to 76%) treated with radiation only (P > 0.2). The median time to progression was 192 days with radiotherapy only compared with 199 days for combined modality therapy (P > 0.2). The median survival time was 313 days compared with 317 days, respectively (P > 0.2). The 1-, 2-, and 5-year survival rates after thoracic radiation only were 45% (Cl, 32% to 58%), 16% (Cl, 6% to 25%), and 7%. With chemoradiotherapy, the survival rates were 46% (Cl, 33% to 60%), 21% (Cl, 11% to 32%), and 5%, respectively. Myelosuppression was significantly greater for the combined modality therapy arm (P = 0.002). ▪ Conclusion: Chemotherapy with MACC, in combination with thoracic radiotherapy, did not result in significant survival advantage compared with radiation alone (P > 0.2) in patients with medically inoperable or unresectable stage III non-small cell lung cancer.
Ectopic Production of the Isolated Beta Subunit of Human Chorionic Gonadotropin
Authors: Bruce D. Weintraub, Saul W. Rosen
Journal: Journal of Clinical Investigation (1973)

A material similar to the beta subunit of human chorionic gonadotropin (hCG-beta) was detected in serum (300 ng/ml) and tumor extract from a 75-yr-old man with pancreatic adenosquamous carcinoma. This material was indistinguishable from hCG-beta in three different types of radioimmunoassay that displayed widely varying reactions with glycoprotein trophic hormones and their subunits. In gel chromatography there appeared to be heterogeneity of the serum beta-like immunoactivity, including one component that coeluted with standard hCG-beta tracer and another immunologically indistinguishable component that displayed a slightly lower elution volume. Neither complete human chorionic gonadotropin (hCG) nor its alpha subunit was detected in radioimmunoassays of serum, before or after fractionation, or in tumor extract. The absence of complete hCG was confirmed in a gonadotropin bioassay sensitive to 15 ng of hCG, which showed no bioactivity in serum or tumor extract containing 450 and 90 ng of hCG-beta, respectively. This case probably represents the first demonstration of isolated polypeptide subunit production of ectopic origin and suggests that hCG-beta, as well as other subunits, may prove useful as cancer markers.
Social deprivation increases workload in palliative care of terminally ill patients
Authors: C R Clark
Journal: BMJ (1997)

Editor-I was interested to read Worrall et al 's study of workload and social disadvantage.1 A reported limitation of their study was the absence of terminally ill patients. At St Christopher's Hospice, we have analysed workload and found substantial differences in palliative care provided in the community that support their findings.

We provide …
THE OXYGEN SATURATION OF HEMOGLOBIN IN THE ARTERIAL BLOOD OF EXERCISING PATIENTS
Authors: Harold E. Himwich, Robert O. Loebel
Journal: Journal of Clinical Investigation (1927)

SATURATION IN ARTERIAL BLOOD hemoglobin occurring in the lungs when the various factors involved in the process are changed by disease. EXPERIMENTALThe present report is concerned with the response of several abnormal individuals to exercise.Nine patients were studied, one with Oxygen content, TABLE 1 oxygen capacity, and saturation of hemoglobin, before, during and after short periods of exercise in patients Oxygen Oxygen Percentage content of capacity saturation arterial of arterial of hemoblood blood globin Disease Patient Date f WilliamR.
Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study
Authors: Katarina Le Blanc, Francesco Frassoni, Lynne Ball, Franco Locatelli, Helene Roelofs, Ian Lewis, Edoardo Lanino, Berit Sundberg, Maria Ester Bernardo, Mats Remberger, Giorgio Dini, R Maarten Egeler, Andrea Bacigalupo, Willem Fibbe, Olle Ringdén
Journal: The Lancet (2008)
Cardiovascular and metabolic effects of CPAP in obese males with OSA
Authors: S. R. Coughlin, L. Mawdsley, J. A. Mugarza, J. P. H. Wilding, P. M. A. Calverley
Journal: European Respiratory Journal (2007)

Obstructive sleep apnoea is associated with increased blood pressure and other features of the metabolic syndrome. The aim of the present study was to determine the relative effectiveness of continuous positive airway pressure (CPAP) in modifying these outcomes. A randomised placebo-controlled blinded crossover trial comparing cardiovascular and metabolic outcomes after 6 weeks of therapeutic and sham CPAP was performed in 34 CPAP-naïve patients (mean±sd body mass and respiratory disturbance indices were 36.1±7.6 and 39.7±13.8, respectively). Mean waking systolic and diastolic blood pressure fell by 6.7 and 4.9 mmHg, respectively, when compared with sham CPAP. No change was observed in glucose, lipids, insulin resistance or the proportion of patients with metabolic syndrome. In CPAP-compliant patients the fall in blood pressure was greater and the baroreceptor sensitivity improved significantly but no metabolic variable changed. In obese Caucasians with untreated obstructive sleep apnoea, continuous positive airways pressure can improve baroreceptor responsiveness and reduce waking blood pressure within 6 weeks, but this treatment period was insufficient to modify insulin resistance or change the metabolic profile. The mechanisms underlying this difference in the time course of blood pressure and metabolic response to continuous positive airway pressure in obstructive sleep apnoea requires further exploration.
Object recognition is not predication
Authors: Jean-Louis Dessalles, Laleh Ghadakpour
Journal: Behavioral and Brain Sciences (2003)

Predicates involved in language and reasoning are claimed to radically differ from categories applied to objects. Human predicates are the cognitive result of a contrast between perceived objects. Object recognition alone cannot generate such operations as modification and explicit negation. The mechanism studied by Hurford constitutes at best an evolutionary prerequisite of human predication ability.
Central Sleep Apnea Induces Ventricular Bigeminus
Authors: Jan Börgel, Andreas Mügge
Journal: Circulation (2008)

V entricular ectopy 1 and central sleep apnea 2 are indepen- dent negative predictors of excess mortality in patients with heart failure.Recent studies have established an association between central sleep apnea and ventricular ectopy. 3ecause the 2 conditions share many common risk factors, however, a causal relationship remains unclear.Here, we present images of a nocturnal polygraphy that provide evidence for a causal relationship between central sleep apnea and ventricular ectopic beats.A 79-year-old man (body mass index, 24.8 kg/m 2 ; height, 1.74 m) with known ischemic heart failure (ejection fraction, 30%) was admitted with suspected cardiac syncopes.The 24-hour ECG revealed frequent monomorphic ventricular ectopic beats with intermittent episodes of a bigeminus.
Tunbridge Wells Infirmary and Dispensary
Authors: J. M. Barry
Journal: BMJ (1858)

THE following cases of dipbtheritis are reported for the purpose of directing attention to the post mortem appearances in the fatal cases, more especially to the presence of fibrinous concre- tions in the right cavities of the heart, and also to illustrate the treatment that has been found most successful.I am indebted to Arthur J. Cribb, M.B., our house-surgeon, for the notes of some of the cases which were more peculiarly under his care.CASE i. Fanny Knight, aged 5, a lively, intelligent girl, previously in the enjoyment of good health, was admitted, on March 1st, 1858.On the 24th of February, she had some cough and hoarseness.On the 25th, she was considered to be better.On Feb. 26th, she had more cough, and oppression of breathing, and had a restless night.On the 27th, she appeared to be better.On the morning of the 28th, she had violent fits of coughing, attended with expectoration of " thick phlegm."At 11 A.M. she was seen for the first time by Mr. Cribb, our house-surgeon, who found the neck swollen externally; some greyish exudation on the tonsils and back of the throat; a sanious discharge from the nostrils occasionally; cough occurring at rare intervals when excited by the presence of the membranous exudation, and relieved by its expulsion; ap- parently not any dyspnoma, no complaint of pain; the respira- tions slow and prolonged, the air entering feebly but freely into the lungs; pulse rapid, very feeble.The throat was sponged with strong solution of nitrate of silver, and stimulants and nourishment freely administered.She died suddenly, about 2 P.M., the same day.SECTIO CADAVERIs,,March 1st, 24 hours after death.The
Rapidly Alternating COPP/ABV/IMEP Is Not Superior to Conventional Alternating COPP/ABVD in Combination With Extended-Field Radiotherapy in Intermediate-Stage Hodgkin's Lymphoma: Final Results of the German Hodgkin's Lymphoma Study Group Trial HD5
Authors: M. Sieber
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To investigate whether treatment results in intermediate-stage Hodgkin’s lymphoma can be improved by rapid application of non–cross-resistant drugs, the 10-drug regimen cyclophosphamide, vincristine, procarbazine, and prednisone (COPP), doxorubicin, bleomycin, and vinblastine (ABV), and ifosfamide, methotrexate, etoposide, and prednisone (IMEP), repeated every 6 weeks, was compared with conventional alternating COPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) administered every 8 weeks. PATIENTS AND METHODS: From January 1988 to January 1993, 996 patients in stage I or II Hodgkin’s lymphoma with at least one risk factor (massive mediastinal tumor, massive spleen involvement, extranodal disease, elevated ESR, or more than two lymph node areas involved) and all patients in stage IIIA Hodgkin’s lymphoma were randomized to receive two cycles of COPP/ABVD or COPP/ABV/IMEP followed by extended-field radiotherapy. RESULTS: Both regimens produced similar rates for treatment responses (com...
Cardiotrophin-1 (CT-1) can protect the adult heart from injury when added both prior to ischaemia and at reperfusion
Authors: Z Liao
Journal: Cardiovascular Research (2002)

Objectives: To determine whether the cytokine cardiotrophin-1 (CT-1) can protect the adult heart against ischaemia/reperfusion when added either prior to ischaemia or at reperfusion. Background: CT-1 has previously been shown to protect cultured embryonic or neonatal cardiocytes from cell death. To assess the therapeutic potential of CT-1, it is necessary to determine whether this effect can be observed in adult cardiac cells both in culture and most importantly in the intact heart. Methods: We examined the protective effect of CT-1 both in cultured adult rat cardiocytes and in the rat intact heart. In both cases, the cardiac cells were exposed to hypoxia/ischaemia followed by reoxygenation/reperfusion and CT-1 was administered either prior to hypoxia/ischaemia or at reoxygenation/reperfusion. Results: CT-1 has a protective effect in reducing ischaemic damage in the intact heart ex vivo as assayed by infarct size to area at risk ratio (20% compared to 35%). Similar protective effects against cell death were noted in adult cells in vitro. Both in vitro and ex vivo CT-1 can exert a protective effect when added at the time of reoxygenation/reperfusion as well as prior to the hypoxic/ischaemic stimulus (cell death reduced from 50 to 20% in TUNEL assay, infarct size to zone at risk ratio reduced from 35 to 20%). These protective effects are blocked by an inhibitor of the p42/p44 MAPK pathway. Conclusion: CT-1 can protect adult cardiac cells both in vitro and in vivo when added both prior to or after the hypoxic/ischaemic stimulus. The potential therapeutic benefit of CT-1 when added at the time of reperfusion following ischaemic damage is discussed.
ETIOLOGY OF OROYA FEVER
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1926)

1. Animals immunized with the formalinized filtrates of young toxic cultures of B. botulinus produce an antitoxic serum poor in precipitins. 2. Animals immunized with the formalinized filtrates of old and partly autolyzed toxic cultures produce an antitoxic serum containing precipitins. 3. Animals immunized with toxin-free autolyzed bacteria produce a serum free from antitoxin but rich in specific precipitins. 4. Animals immunized with the filtrates of an atoxic variant produce a serum free from antitoxin but rich in precipitins for the homologous toxin. 5. Animals immunized with the washed bacteria of the atoxic variant produce a serum that contains no antitoxin, but is rich in precipitins for the homologous toxin. 6. Removal of the precipitins by flocculation with a non-toxic antigen does not materially reduce the antitoxic value of a serum. 7. Removal of the proteins of the antigen by add coagulation removes the specific precipitable substance. 8. All the sera that contain precipitins produce the specific flocculus when combined with homologous toxins, anatoxins, or with the filtrates of the atoxic variant. The flocculation is restricted within the type. The amount of the precipitate and the width of the zone vary approximately with the estimated amount of bacterial protein in the antigen that is used for the immunization of animals. We conclude, therefore, that the toxin-antitoxin flocculation is a specific bacterial precipitation phenomenon.
Spirochaetosis of the human rectum associated with an intraepithelial mast cell and IgE plasma cell response.
Authors: J O Gebbers, D J Ferguson, C Mason, P Kelly, D P Jewell
Journal: Gut (1987)

In two patients presenting with mild intestinal symptoms, rectal spirochaetosis was the only morphological abnormality diagnosed by light microscopy. A re-evaluation of the morphological changes using electron microscopy and immunohistochemistry showed certain unusual features: the microorganisms were observed within epithelial cells and in subepithelial macrophages; there were numerous partially degranulated intraepithelial mast cells; and there was a marked increase in the proportion of IgE plasma cells within the lamina propria. Mucosal penetration by the organisms may be responsible for the unusual immune response. In one patient, treatment with antibiotics eliminated the spirochaetes and resulted in a clinical improvement. Spirochaetes should not always be considered as harmless commensals in the colon.
Curcumin improves sclerosing cholangitis in Mdr2-/- mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation
Authors: A. Baghdasaryan, T. Claudel, A. Kosters, J. Gumhold, D. Silbert, A. Thuringer, K. Leski, P. Fickert, S. J Karpen, M. Trauner
Journal: Gut (2010)

Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. Curcumin, the yellow pigment of the spice turmeric, has pleiotropic actions and attenuates hepatic damage in animal models of chemically-induced liver injury. Whether curcumin has beneficial effects in cholangiopathies is unknown.Potential anticholestatic, anti-inflammatory and antifibrotic mechanisms of curcumin were explored in vivo in Mdr2(-/-) mice as a murine model of chronic cholangiopathy; as well as in vitro in a cholangiocyte cell line (HuCCT1) and portal myofibroblasts (MFBs) isolated from Mdr2(-/-) mice.Liver damage, cholestasis and fibrosis were reduced in Mdr2(-/-) mice after curcumin feeding. Moreover, curcumin inhibited cholangiocyte proliferation and expression of activation marker vascular cell adhesion molecule-1 in Mdr2(-/-) mice. Curcumin-similar to PPARgamma synthetic agonist troglitazone-directly inhibited TNF-alpha-induced inflammatory activation of cholangiocytes in vitro, whereas these beneficial effects of curcumin were largely blocked by a PPARgamma synthetic antagonist. In addition, curcumin blocked proliferation and activation of portal MFBs by inhibiting ERK1/2 phosphorylation, thus contributing to reduced fibrogenesis.These results show that curcumin may have multiple targets in liver including activation of PPARgamma in cholangiocytes and inhibition of ERK1/2 signalling in MFBs, thereby modulating several central cellular events in a mouse model of cholangiopathy. Targeting these pathways may be a promising therapeutic approach to cholangiopathies.