tbuckley/cabot-search huggingface dataset:
Abstract 9579: Inhibition of Adverse Myocardial Remodeling and Improvement of Cardiac Function with Postconditioning: Comparison with Preconditioning
Authors: Ning-Ping Wang, Zhang-Feng Wang, Tiji Philip, Zhi-Qing Zhao
Journal: Circulation (2011)

We have reported that postconditioning (Postcon) reduces infarct size and preserves cardiac function during extended reperfusion. This study tested the hypothesis that modulation of adverse cardiac remodeling with Postcon is associated with enhancement of angiogenesis and prevention of fibrosis by recruiting host myofibroblasts. Fifty-eight rats were subjected to 45 min ischemia followed by 7 and 42 d reperfusion, respectively. Four cycles of 10/10 s Postcon or two cycles of 5/5 min preconditioning (Precon) were applied at the onset of reperfusion or before ischemia, respectively. At 7 d reperfusion, expression of collagen I and III (Western blot) was significantly down-regulated (85±8* and 89±6* vs. 128±10 Abr. u), and MMP2/TIMP4 ratio (Zymography) was reduced (0.9±0.2* and 1.0±0.6* vs. 4.1±0.8) in the Postcon and Precon groups relative to the Control. The population of myofibroblasts (immunohistological staining) within the infarct area increased significantly relative to the Control (78±9* and 69±10* vs. 45±3//HPF) in these two groups, consistent with significantly enhanced immunoreactivity of VEGF. Along with these changes, angiogenesis was significantly enhanced relative to the Control, evidenced by increased number of α-smooth muscle actin-positive vessels (38±4*, 31±8* vs. 12±3/HPF) and vWF-positive vessels (45±4*, 41±7* vs. 22±5/HPF), respectively. At 42 d reperfusion, histological examination with Masson Trichome staining revealed that the extension of fibrotic zone was markedly reduced with increased mass of viable myocardium in the Postcon and Precon groups. Furthermore, echocardiography showed improvements in end-systolic volume (0.5±0.1*, 0.4±0.2* vs. 0.8±0.3 ml), fractional shortening (29±5*, 27±7* vs. 22±4%) and ejection fraction (56±9*, 50±6* vs. 39±7%) in the Postcon and Precon groups compared with the Control. The wall thickness of the infarct middle anterior septum in the Postcon and Precon was significantly greater than that in the Control (1.7±0.01*, 1.6±0.02* vs. 1.1±0.01 mm). We conclude that Postcon and Precon inhibit adverse myocardial remodeling and preserve cardiac function, potentially mediated by proliferated myofibroblasts and enhanced angiogenesis. * P&lt;0.05 Postcon and Precon vs. Control.
Cognitive functioning in late-life schizophrenia: a comparison of elderly schizophrenic patients and patients with Alzheimer's disease
Authors: M Davidson, P Harvey, K A Welsh, P Powchik, K M Putnam, R C Mohs
Journal: American Journal of Psychiatry (1996)

Previous studies have suggested that geriatric inpatients with chronic schizophrenia manifest profound cognitive impairments. This study investigated how these cognitive impairments resemble those seen in degenerative dementing conditions.The neuropsychological battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), widely used to characterize the cognitive deficits of patients with Alzheimer's disease, was used to compare patterns of cognitive impairment in 66 triads of subjects consisting of one elderly patient with Alzheimer's disease, one elderly, institutionalized patient with chronic schizophrenia, and one elderly, cognitively normal comparison subject who were matched on age, gender, and education. For some analyses, the two groups of patients were divided into subgroups according to the degree of their cognitive impairment (mild, moderate, or severe) as determined by their scores on the Mini-Mental State examination.Relative to the comparison subjects, both groups of patients showed cognitive deficits on each of the neuropsychological measures. The schizophrenic patients performed worse than the patients with Alzheimer's disease on tests of naming and constructional praxis but were less impaired on the test of delayed word recall. These differences were consistent across all levels of severity of globally measured cognitive impairment.Consistent with earlier findings from postmortem studies, these findings suggest that major differences exist in the neurobiologic mechanisms responsible for cognitive impairment in schizophrenia and Alzheimer's disease. Effects directly attributable to social and environmental differences between these two groups of patients may also play a role.
El valor de captacion estandarizado (SUVmax) del tumor primario medido con tomografia de emission de postrones con fluorodesoxiglucosa (FDG-PET) tiene valor pronostico para la supervivencia en el cancer de pulmon no microcitico (CPNMC): Una revision sistematica y metaanalisis (MA) del European Lung Cancer Working Party para el IASLC Lung Cancer Staging Project
Authors: Thierry Berghmans, Michèle Dusart, Marianne Paesmans, Claude Hossein-Foucher, I Buvat, Catherine Castaigne, Arnaud Scherpereel, Céline Mascaux, Michel Moreau, Marcel Roelandts, Serge Alard, Anne-Pascale Meert, E.J. Patz, Jean-Jacques Lafitte, Jean-Paul Sculier
Journal: Journal of Thoracic Oncology (2008)
Methadone treatment can reduce mortality
Authors: W. Poser, J. Koc, H. Ehrenreich
Journal: BMJ (1995)

<b>Background</b> Autoantibodies specific for the acetylcholine receptor (AChR) of skeletal muscle (containing the α1 subunit) impair neuromuscular transmission in myasthenia gravis (MG). AChRs mediating fast synaptic transmission through autonomic ganglia are structurally similar to muscle AChR, but contain the α3 subunit. We propose that ganglionic AChR autoimmunity may cause dysautonomia. <b>Objective</b> To test serum of patients with autonomic neuropathy for autoantibodies of neuronal ganglionic AChR specificity. <b>Methods</b> We developed an immunoprecipitation radioassay by complexing epibatidine (<sup>125</sup>I-labeled high affinity agonist) to a Triton X-100-solubilized AChR antigen from peripheral neuroblastoma membranes. Monoclonal rat immunoglobulins (IgG) specific for muscle or neuronal AChRs validated the assay9s specificity. We tested serum from 52 healthy subjects, 12 patients with subacute autonomic neuropathy, and 248 patients with other neurologic disorders. <b>Results</b> Twelve patients had antibodies that bound unequivocally to ganglionic AChR. Five had subacute autonomic neuropathy, and three (of six tested) had Isaacs9 syndrome; four of these eight had a carcinoma (lung, bladder, rectum, thyroid). The remaining four seropositive patients (two Lambert-Eaton syndrome, one dementia, one sensory neuronopathy) all had Ca<sup>2+</sup> channel antibodies and three had small cell lung carcinoma. No healthy subject had ganglionic AChR antibodies, nor did 62 patients with MG and muscle AChR antibodies. <b>Conclusion</b> Neuronal AChR antibodies are a novel serologic marker of neurologic autoimmunity. The pathogenicity of neuronal AChR autoantibodies in autonomic neuropathy, Isaacs9 syndrome, or other neurologic disorders remains to be shown, as has been demonstrated for muscle AChR antibodies in MG. An autoimmune and potentially paraneoplastic etiology is implicated in seropositive patients.
Phase I study of pemetrexed in patients with relapsed or refractory acute leukemia or lymphoid blast phase chronic myelogenous leukemia
Authors: W. Plunkett, D. A. Thomas, S. M. O'Brien, S. Federl, F. J. Giles, S. J. Nicol, J. Gill, L. Zhao, F. Ravandi, H. Kantarjian
Journal: Journal of Clinical Oncology (2009)

7068 Background: Pemetrexed is a folate antimetabolite that is clinically active in a number of different cancers. The purpose of this phase I trial was to define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended phase II dose (RP2D) of pemetrexed given with vitamin supplementation to patients with relapsed or refractory leukemia. Secondary objectives were pharmacokinetic (PK) and pharmacodynamic (PD) analyses of pemetrexed. Methods: Patients ≥15 years of age were enrolled with relapsed or refractory leukemia, Eastern Cooperative Oncology Group performance status ≤2, adequate renal and hepatic function, and life expectancy of ≥6 weeks. Enrollment was planned using a 3+3 dose escalation design. Intravenous pemetrexed was given at a starting dose of 900 mg/m 2 over 1 hour every 3–4 weeks. Doses were escalated to 1,200, 1,500, 2,000, 2,700, and 3,600 mg/m 2 . Folic acid and Vitamin B 12 were given with pemetrexed. Response was assessed by standard blood and bone marrow criteria. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0. Results: Twenty-two patients entered the trial; median age was 50 years (range: 18–75); 15 patients had acute myeloid leukemia and 7 patients had acute lymphocytic leukemia (ALL). Two patients were ineligible and did not receive study drug. At the 1,200 and 1,500 mg/m 2 dose levels, 1 patient per level developed grade (G) 3–4 liver enzyme and bilirubin elevations attributed to sepsis. At the 3,600 mg/m 2 dose level, 1 patient had a G3 liver enzyme elevation and 2 added patients also had G3 liver toxicity. In addition, 2 patients in the 3,600 mg/m 2 cohort developed G2 liver abnormalities. Based on liver toxicities, the DLT dose level was established at 3,600 mg/m 2 . Two patients died during the study due to disease progression and 1 patient discontinued due to a subdural hematoma of unknown cause. One patient with ALL achieved a partial response. There were no other objective responses. PK and PD data were not available for this report. Conclusions: The MTD and RP2D of pemetrexed were determined to be 2,700 mg/m 2 . Due to limited observed efficacy, a planned phase II trial was canceled. [Table: see text]
Venous Thromboembolic Disease
Authors: Lawrence D Wagman, Melissa F Baird, Charles L Bennett, Paula L Bockenstedt, Spero R Cataland, John Fanikos, Patrick F Fogarty, Samuel Z Goldhaber, Tejpal S Grover, William Haire, Hani Hassoun, Suzanne Hutchinson, Mohammad Jahanzeb, Jason Lee, Michael L Linenberger, Michael M Millenson, Thomas L Ortel, Riad Salem, Judy L Smith, Michael B Streiff, Suresh Vedantham
Journal: Journal of the National Comprehensive Cancer Network (2008)

Venous thromboembolism (VTE) is a common, life-threatening condition in patients with cancer, which includes both deep venous thrombosis (DVT) and pulmonary embolism. The occurrence of VTE has been reported to increase the likelihood of death for cancer patients by 2- to 8-fold. Pathophysiologic explanations for VTE in cancer include known hypercoagulability, vessel wall damage, and vessel stasis from direct compression, and the incidence of VTE in cancer is increased by additional risks factors. The NCCN guidelines specifically outline strategies to prevent and treat VTE in adult cancer patients. These guidelines are characterized by evaluations of the therapeutic advantages of pharmacologic anticoagulation measures based on both perceived risk for bleeding (i.e., contraindications to anticoagulation) and cancer status. Important updates for 2008 include new work-up recommendations and changes in the recommendations for outpatient prophylaxis and diagnosis and for treatment of heparin-induced thrombocytopenia. For the most recent version of the guidelines, please visit NCCN.org
G11 : Microbial translocation in liver fibrosis induces chronic IFNAR signaling that impairs innate immunity against bacterial infection
Authors: Z. Abdullah, P. Hackstein, M. Beyer, J. Trebicka, T. Sauerbruch, U. Spengler, J.L. Schultze, C. Kurts, W. Kastenmüller, P.A. Knolle
Journal: Journal of Hepatology (2015)
More on Subgroup Analyses in Clinical Trials
Authors: Stuart J Pocock, Jacobus Lubsen
Journal: New England Journal of Medicine (2008)

To the Editor: With regard to the article by Wang et al. (Nov.22 issue), it is increasingly recognized that subgroup analyses in clinical trials are sometimes misused and require appropriate presentation and cautious interpretation. 1,2However, we would recommend that one type of subgroup analysis (in large "positive" trials or metaanalyses) be performed more often.That is, from a prognostic model, one categorizes patients into several ordered risk groups and estimates the absolute risk reduction in each group.For instance, the Third Randomized Intervention Treatment of Angina (RITA-3) trial, 3 involving patients with acute coronary syndromes, showed an overall reduction in the risk of myocardial infarction or death associated with an invasive strategy as compared with conservative management.Such a riskstratified subgroup analysis then usefully clarified that this benefit was mainly in patients at high risk for myocardial infarction or death.In general, such an approach can be an important aid for clinical practice, so that for any specific patient, one can judge the absolute benefit of a new treatment (set against the absolute risk of side effects, as well as costs if relevant) and decide whether the treatment is warranted for that patient.This approach is also applicable when, with regard to relative risk, there is no evidence of subgroup interactions with treatment.The question of whether prasugrel is preferable to clopidogrel in acute coronary syndromes 4 is an interesting example; it may be that the absolute benefit of the reduced risk of ischemic events outweighs the increased risk of bleeding only for high-risk patients.Similarly, if the absolute risk of myocardial infarction due to rofecoxib (Vioxx) had been properly quantified in appropriate risk-stratified subgroup analyses, the benefits of pain relief and reduced gastrointestinal bleeding might have been more clearly seen to outweigh the low absolute risk of myocardial infarction in a substantial proportion of patients, thus permitting the continued prescription of rofecoxib with appropriately restrictive labeling.
China rejects patent on hepatitis C drug sofosbuvir
Authors: Z. Kmietowicz
Journal: BMJ (2015)

The Chinese patent office has rejected a patent application for the blockbuster hepatitis C treatment sofosbuvir, increasing the possibility of a generic version of the drug to become available in China.

The decision comes after a challenge by the Initiative for Medicines, Access and Knowledge (I-MAK), a US based group that campaigns for better access to affordable drugs. The group claimed that Gilead Sciences, the US biotechnology company that makes sofosbuvir, which recorded sales of more than $10bn in 2014, was seeking “illegitimate patents” for sofosbuvir and “blocking millions …
Preexposure Prophylaxis for HIV Prevention
Authors: Salim S Abdool Karim, Glenda E Gray, Neil Martinson
Journal: New England Journal of Medicine (2012)

c ase vignet tes The first patient, a 46-year-old sexually active man who has sex with men, presents for routine primary care. He lives in New York City and reports that he is in a long-term, stable, open relationship with a male partner and that he has had multiple recent sexual encounters with acquaintances. A recent HIV test was negative. He has seasonal allergies, for which he occasionally takes antihistamines, and chronic lower back pain, for which he takes nonsteroidal antiinflammatory drugs on a regular basis. Otherwise he takes no medications and has no known allergies to medications. He had syphilis 10 years earlier for which he was successfully treated. His physical examination is notable only for the fact that he is uncircumcised. You review HIV prevention strategies in detail with him, including the potential benefits of circumcision and of the use of condoms. He has been reading information on the Internet, including information about preexposure prophylaxis (PrEP), and asks whether he should be receiving this therapy. The second patient, an 18-year-old heterosexual woman in South Africa who has recently become sexually active, presents for voluntary HIV testing. She does not know the HIV status of her male partners. She reports no medical problems, is taking no medications, and has no known allergies to medications. She reports that her older sister recently received a diagnosis of HIV infection. Her physical examination is unremarkable. Testing for sexually transmitted infections is performed. A pregnancy test is negative. She would like to initiate birth control and elects to start taking oral contraceptive pills. She returns to the clinic the following week and is informed that all the tests for sexually transmitted infections, including the HIV test, were negative. She thinks that she had received the hepatitis B vaccination series. She is negative for hepatitis B surface antigen. She is given extensive HIV counseling, and the various HIV prevention strategies are reviewed in detail.
Abstract 209: Role Of Apoptosis Inducing Factor In Caspase-independent Apoptosis In Hypertrophic Cardiomyocytes
Authors: Sangita Choudhury, Soochan Bae, Sheetal R Kumar, Qingen Ke, Bhargavi Yalamarti, Lorrie A Kirshenbaum, Peter M Kang
Journal: Circulation (2008)

Caspases are thought to be central mediators of the apoptotic program, but recent data indicate that apoptosis can also be activated by caspase-independent mechanisms, such as via apoptosis inducing factor (AIF). We and others have shown that the hypertrophic heart may be more prone to apoptotic insult. Thus, we seek to investigate the characteristics of AIF-induced cardiac apoptosis in hypertrophic cardiomyocytes  in vitro  and describe its role.   Method:  Hypertrophic (H-CMs) and non-hypertrophic cardiomyocytes (N-CMs) were isolated from Dahl salt sensitive rats fed a high salt or a normal diet for 6 weeks, respectively; exposed to apoptotic stimulation, such as hypoxia/reoxygenation (H/R) or staurosporine (ST); and analyzed for the activation of caspases, AIF and cytochrome c release from mitochondria, and the rate of apoptosis.   Results:  Both H-CMs and N-CMs responded to H/R and ST with a significant release of AIF (evidence of AIF activation), cytochrome c (evidence of caspase-dependent apoptosis), and apoptosis. Apoptotic stimuli did not cause significant caspase activation in H-CMs, but the release of AIF from the mitochondria in these cells was a significant 2.5 times greater than in N-CMs. These results suggest that AIF-induced apoptosis is more prominent in H-CMs. We also found that in N-CMs, inhibiting caspase by adenoviral overexpression of CrmA (a known caspase inhibitor), or pre-treatment with zVAD-fmk (a pan-caspase inhibitor) significantly blocked apoptosis after H/R and ST (39% and 66%, p   Conclusion:  Apoptotic mechanisms in hypertrophic cardiomyocytes appear to be biased towards caspase independent pathways, and therefore the inhibition of AIF-induced apoptosis may be an effective anti-apoptotic therapy in hypertrophic heart.
Getting our house in order
Authors: T. Delamothe
Journal: BMJ (2015)

Anyone with even a fleeting acquaintance with The BMJ will have noticed the words “oseltamivir” (Tamiflu) and “statins” appearing a lot recently. With two online collections devoted to the drugs (thebmj.com/tamiflu and thebmj.com/statins), it may seem that we’ve developed an unhealthy obsession with them. What we’re obsessed with is getting sight of the evidence for oseltamivir’s efficacy and statins’ adverse effects. It could have been any drug; it’s just that these showed up on our radar first.

Alteplase would make an equally worthy candidate for closer scrutiny of both risks and benefits, as our News story shows (doi:10.1136/bmj.h3301). Roger Shinton and three other senior clinicians have called on …
Preliminary safety results from a multicenter phase II trial of nanoparticle albumin-bound paclitaxel/cyclophosphamide in early stage breast cancer plus trastuzumab in HER-2+ patients (pts)
Authors: E. Raefsky, R. Inhorn, M. Lange, N. Peacock, M. Shastry, E. Vazquez, V. Priego, L. Franco, J. D. Hainsworth, D. A. Yardley
Journal: Journal of Clinical Oncology (2009)

e11509 Background: Docetaxel/cyclophosphamide has demonstrated superior disease free and overall survival compared to doxorubicin/cyclophosphamide in the treatment of early stage breast cancer with an acceptable safety profile, with grade (G) 3/4 neutropenia of 61% and no cardiotoxicity. Nanoparticle albumin-bound (nab tm )-paclitaxel (nab-P) is a novel formulation with demonstrated superior efficacy to conventional paclitaxel (P) in treatment of metastatic breast cancer with a comparable safety profile. We therefore conducted a multicenter phase II pilot trial of weekly nab-P/cyclophosphamide to assess the safety and tolerability of this combination in early stage breast cancer. Methods: Eligibility: T1–4pN0–3M0, ECOG PS 0–2, normal organ function, normal LVEF for pts receiving trastuzumab (T). Treatment consisted of nab-P 100 mg/m 2 day (D) 1, 8, 15 with cyclophosphamide (C) 600 mg/m 2 D1 q 21 days x 4 cycles. T was given in IHC 3+ or FISH HER2+ pts with an 8 mg/kg loading dose followed by 6mg/kg q21D x 52 weeks. Results: 63 pts enrolled from April 2008 through September 2008; 33 pts are evaluable for safety with a median of 2 cycles. Baseline characteristics: median age 57 years (range 33–76); ECOG PS 0–94%, T1-T2 tumors - 100%, node negative 61%, hormone receptor negative 33%, HER 2+ 15%, triple negative 27%, ductal histology 73%, premenopausal 37 %. nab-P dose modifications occurred in 10 of 33 pts with nab-P reductions in 2 pts: 1 each due to G3 neutropenia- cycle 2 and G3 neuropathy- cycle 4. All 8 nab-P treatment delays were due to G3 neutropenia at D15. G3/4 neutropenia was present in 30% with only 1 G4 episode. 1 pt utilized myeloid colony stimulating factors. There were no G3/4 non-heme toxicities present in &gt; 5 % of pts and no LVEF declines in pts receiving T. 17 pts remain on study with 3 pts receiving T. Conclusions: The combination of weekly nab-P with cyclophosphamide is feasible and well tolerated with an acceptable safety profile as adjuvant therapy for early stage breast cancer. The addition of T to this combination did not create any safety concerns. Full safety data for the 63 pts will be updated at the time of the meeting. [Table: see text]
Abstract 10954: Magnetocardiography Can Disclose Left Intraventricular Conduction Delay in Patients with Left Ventricular Dysfunction and Complete Right Bundle Branch Block
Authors: Shoji Kawakami, Hiroshi Takaki, Shuji Hashimoto, Yuko Yamada, Hideo Okamura, Takashi Noda, Kazuhiro Satomi, Takeshi Aiba, Wataru Shimizu, Naohiko Aihara, Shiro Kamakura, Masaru Sugimachi
Journal: Circulation (2011)
Clusters of infectious diseases in German nursing homes – observations from a prospective infection surveillance study, October 2008 to August 2009
Authors: M Schulz, M Mielke, N Wischnewski
Journal: Eurosurveillance (2011)

A prospective infection surveillance study was carried out among residents of seven nursing homes in and around Berlin, Germany, from October 2008 to August 2009. A considerable number of infections were found to occur in clusters. Active surveillance was carried out using pre-established case definitions of infections in nursing homes (McGeer criteria). Case finding was based on routine nursing files. Infection rates were calculated per 1,000 resident days. Clusters were identified using a pre-established definition. In total 511 residents were observed during 74,626 resident days (rd), and 393 infections occurred in 243 participants, giving an overall incidence of infection of 5.3 per 1,000 rd. The most common infections were gastrointestinal infections (n=122; 1.6/1,000 rd), acute respiratory disease (n=86; 1.2/1,000 rd) and urinary tract infections (n=71; 1.0/1,000 rd). Seven clusters involving 74 infections in 57 residents were observed: three of acute respiratory disease, three of acute gastrointestinal disease and one of conjunctivitis. Attack rates varied between 11% and 61%. Clusters occurred frequently in the observed nursing homes and could be detected by infection surveillance based on routine documentation.