tbuckley/cabot-search huggingface dataset:
The Surgical Relief of Pain
Authors: L. Rogers
Journal: BMJ (1952)

Remembering that pain is but a symptom and its bio- logical purpose for the most part protective, we must seek to allay its cause.This may, however, be unknown or imperfectly understood, as in trigeminal neuralgia, or well known but no longer within the range of effective local treatment, as in myocardial ischaemia or inoperable malignant disease.In such cases our efforts must be wholly directed to relieving the symptom of pain.Sur- gical methods for its relief will usually be considered only after lesser measures in the form of anodynes have failed or for any reason are no longer advisable.Pain may be relieved or abolished by:(1) Removing its source, thereby eliminating the noxious impulses which are giving rise to it-for example, the pain of appendicitis by appendicectomy, of gallstones or renal colic by getting rid of the offending calculi.(2) The administration of anaesthetics-for example, in tetanic spasms-or analgesic drugs-for example, morphine in cardiac infarction.(3) The interruption of the pathways of the painful impulses in order to abolish or modify their effects on the sensorium, either before they reach it or in the brain itself, by operations such as neurotomy, rhizotomy, chordotomy, medullary or mesencephalic tractotomy, or frontal lobotomy.(4) Increasing the blood supply to the painful part so as to reduce or abolish the pain of ischaemia.We should also remember that irradiation will sometimes diminish the pain of malignant disease, though for a time it may make the patient feel very ill.
Abstract 17489: Regional Strain Shows Greater Interplatform Variability Than Global Strain
Authors: Shafkat Anwar, Patrick Gladding, Kazuaki Negishi, Zoran Popovic, James D Thomas
Journal: Circulation (2011)

Introduction: Strain (S) analysis is a useful adjunct to conventional echocardiography but is limited by vendor-specific restrictions. Analysis of DICOM (D) images enables extraction of S regardless of image source. Existing data show good agreement in Global (G) Longitudinal S values between native polar (P) and processed D images. To further evaluate agreement we compared Regional S (RS) values from the same images in P &amp; D formats. Hypothesis: RS values will have variability between P &amp; D analysis. We will accept good agreement if there is no significant difference in mean RS values in P and D analysis, and if the correlation coefficient (r) is ≥ 0.85. Methods: 20 patients (54 +/− 12 years) had echocardiograms with a General Electric (GE) Vivid 7 scanner: 7 normals, 13 cardiomyopathies. 4,3 &amp; 2-chamber LV apical views yielding 60 datasets were analyzed using EchoPAC (GE, version 10.8.1) in P format and Velocity Vector Imaging (VVI, Siemens, version 3.5) in D format by 3 blinded observers. RS data was analyzed using an 18-segment LV model. Results: While agreement for GS was good (r=0.90, p&lt;0.0001), there was low (though generally significant, p&lt;0.05) correlation between P &amp; D RS. 1 segment showed r ≥ 0.85, with 6 segments showing r ≥ 0.75 (Table 1). D images yielded lower S in magnitude in 13 of 18 segments (mean P-D -2.1, range -5.0 to 1.47). There was low inter-observer agreement for RS (Table 2). Conclusion: LV Longitudinal RS from DICOM images do not agree well with native Polar S for the majority of cardiac segments, with fairly high inter-observer variability. Higher agreement for GS is likely due to averaging of RS across LV segments. Standardization efforts are essential to address this issue.
Abstract 3636: Ekg Left Ventricular Hypertrophy And Cardiovascular Events In Patients With Type 1 And Type 2 Diabetes Mellitus
Authors: Massimo Salvetti, Maria Lorenza Muiesan, Barbara Stanga, Antonio Cimino, Umberto Valentini, Anna Paini, Eugenia Belotti, Linda Micheletti, Carlo Aggiusti, Claudia Agabiti Rosei, Valentina Paderno, Enrico Agabiti Rosei
Journal: Circulation (2007)

Background: A large number of studies have demonstrated that LVH detected with standard electrocardiography is an independent predictor of future cardiovascular complications in various subsets of patients. Despite the fact that ECG represents the first cardiovascular test performed in diabetics, few data are available on the prognostic significance of EKG LVH in these patients. Aim of this study was to evaluate the relationship between EKG LVH and the risk of future cardiovascular events in a wide group of patients with diabetes mellitus (DM). Methods A total of 1131 prospectively identified patients with type 1 (n=613, age 36 ± 13 years, 40 % women, BP 127 ± 16/79 ± 8 mmHg, total cholesterol 196 ± 43 mg/dl, HbA1C 7.81 ± 1.67%) and with type 2 DM (n=618, age 53 ± 11 years, 34 % women, BP 137 ± 18/82 ± 8 mmHg, total cholesterol 208 ± 41 mg/dl, HbA1C 7.97 ± 1.72%) were studied. At baseline all subjects underwent baseline clinical examination with blood pressure measurement according to current guidelines, standard laboratory examinations and a 12 leads electrocardiogram. LVH was defined as the presence of a “Sokolow-Lyon” voltage &gt;38 mm and/or a “Cornell voltage QRS duration product” &gt;2440 mm* msec. Treatment was not standardized. Results LVH prevalence was 8.3 % in type 2 DM and 6.4 % in type 1 DM. Patients were followed for 63 ± 27 months (range 1–126). A first non fatal cardiovascular event occurred in 62 patients. Kaplan-Meyer analysis revealed a higher risk of cardiovascular events in patients with LVH both with type 1 and type 2 DM (Log Rank Mantel Cox p&lt;0.01). In Cox analysis, controlling for age, gender, BMI, history of cardiovascular disease, systolic blood pressure, heart rate, total plasma cholesterol, HbA1c, albuminuria and antihypertensive treatment, the presence of LVH was associated with an increased risk of cardiovascular events in all patients (odds ratio 2.96, 95% CI 1.39 to 6.32, p&lt;0.01) and separately in DM type 1 (odds ratio 5.71, 95% CI 1.29 to 25.17, p=0.02) and in type 2 DM (odds ratio 2.92, 95% CI 1.02 to 8.35, p=0.05). Conclusions: Our data demonstrate that in patients with DM the detection of LVH by EKG is associated to an increased risk of cardiovascular events, independently of other risk factors and represent the first demonstration of the prognostic significance of EKG-LVH in patients with type 1 diabetes
Treatment of hepatitis C infection
Authors: K. Agarwal, D. D E Jones, M McCarthy, M Wilkinson
Journal: BMJ (1999)

Editor—We were disappointed that McCarthy and Wilkinson’s review of recent advances in hepatology underplayed important public health issues and treatment options surrounding hepatitis C virus.1 In Western Europe about 5 million people are chronic carriers of hepatitis C virus, and in industrialised countries the virus accounts for 40% of cases of end stage cirrhosis and 30% of liver transplants.2 Hepatitis C is thus an important health problem.

Recent data confirm that combination antiviral treatment with ribavirin and interferon is better than interferon alone, with a 38-43% sustained response rate (polymerase chain reaction negative) with 12 months of combination treatment compared with 13-19% with interferon alone.3,4 Although ribavirin has been supplied for use only in trials in the United Kingdom, it is imminently to be licensed for patients who relapse after interferon alone and is already licensed for this indication in the United States and other European countries.

Moreover, a recent international consensus conference on hepatitis C recommended that interferon and ribavirin be first line treatment for previously untreated (naive) patients without contraindication to ribavirin. Duration of treatment should be tailored to viral load and viral genotype. It was suggested that patients with viral genotype 1 should have a six month course of combination treatment before viral response to treatment is assessed compared with three months for those infected with other viral genotypes. These recommendations (drawn from a panel of experts) have important public health and economic implications.

Lastly, we are not aware of any large trials using ribavirin alone in patients with recurrent hepatitis C infection after transplantation as it has little in vitro activity against the virus. Preliminary data on 122 patients with chronic recurrent infection after transplantation from Italy suggest that sustained response rates of up to 50% (similar to that in chronic non-immunocompromised hepatitis C infection) can be obtained safely in selected groups without precipitating graft rejection.5 Patients with coexistent HIV infection should be considered for antiviral treatment of hepatitis C if HIV disease activity is stable. We must be aware of improvements in treatment options for hepatitis C and the public health issues surrounding these advances, particularly in an environment where health resources are finite.
Addition of Inhaled Treprostinil to Oral Therapy for Pulmonary Arterial Hypertension
Authors: Vallerie V. McLaughlin, Raymond L. Benza, Lewis J. Rubin, Richard N. Channick, Robert Voswinckel, Victor F. Tapson, Ivan M. Robbins, Horst Olschewski, Melvyn Rubenfire, Werner Seeger
Journal: Journal of the American College of Cardiology (2010)
The plasma membrane calcium pump in MCF-7 breast cancer cells
Authors: Won Jae Lee, Sarah J. Roberts-Thomson, Jodie A. Robinson, Gregory R. Monteith
Journal: Cancer Research (2005)

3666  In these studies we assessed the consequences of inhibition of the plasma membrane calcium-ATPase (PMCA) in MCF-7 breast cancer cells and the expression of PMCA isoforms in a bank of breast cell lines. Calcium (Ca2+) as an intracellular messenger is essential for countless cellular processes. An increasing awareness of the importance of Ca2+ signaling in the regulation of the cancerous phenotype is emerging. The PMCA is an influential modulator of Ca2+ signals and may have roles in regulating lactation and differentiation of the breast. The existence of four PMCA isoforms and alternative splice variants with different biochemical properties also suggests that PMCA expression is tailored to suit specific functional roles. In order to understand the potential importance of the PMCA in breast cancer we generated stable MCF-7 Tet-off cell lines that were designed to express antisense transcripts targeting all PMCA isoforms and assessed the expression of PMCA isoforms in a bank of normal and tumorigenic breast cell lines. We assessed PMCA expression using western blotting and PMCA-mediated Ca2+ efflux, by assessing the recovery of intracellular free Ca2+ in cells loaded with a Ca2+-sensitive dye in buffer designed to inhibit sarco/endoplasmic reticulum ATPase-mediated Ca2+ sequestration and Na+/Ca2+-exhanger-mediated Ca2+ efflux. Cellular proliferation was assessed using an MTS assay and cell cycle changes were assessed using fluorescence activated cell sorting. PMCA isoform mRNA was quantitated using real time RT-PCR for PMCA1, PMCA2 and PMCA4. We found that PMCA antisense produced significant alterations in PMCA protein expression, PMCA-mediated intracellular Ca2+ efflux and cell proliferation upon antisense induction. In addition, PMCA antisense expression mediated effects on cell proliferation may involve changes in cell cycle kinetics. Significant differences in PMCA1, PMCA4 and most notably PMCA2 (an isoform abundantly found in neurons and other excitable cells) were detected between the breast cell lines examined. A clear correlation between levels of PMCA isoform expression and tumorigenicity did not exist. However, differential expression levels of PMCA isoforms may be linked with mammary gland differentiation status. Together, our data point to the important effects modulation of PMCA expression and activity may have in regulating proliferation and differentiation in the breast. Thus, the PMCA may represent a viable drug target for the adjuvant treatment of breast cancer and future studies should evaluate this potential.
Abstract 9673: Mesenchymal Stem Cells Modulate Inflammatory Responses in Murine Heart by Inhibition of the TNF System
Authors: Alessandra Martire, Fikru Belema Bedada, Shizuka Uchida, Joechen Poeling, Astrid Wietelmann, Markus Krueger, Thomas Kubin, Marten Szibor, Henning Warnecke, Thomas Braun
Journal: Circulation (2011)

Mesenchymal stem cells have been used to treat numerous different clinical conditions, although the mechanisms by which pathogenetic processes are affected are still poorly understood. We have recently demonstrated the homing of murine long-term renewing adult bone marrow-derived multipotent mesenchymal stem cells (BM-MASCs) to diseased tissues and postulated that BM-MASCs might modulate inflammatory reactions. We here show that administration of BM-MASCs modulates adverse cardiac remodeling inhibiting the TNF system in a transgenic mouse model of cardiac-specific expression of MCP-1-induced inflammatory dilative cardiomyopathy. Four-months old MCP-1 mice were analyzed before and after 4-week administration of MASCs, Etanercept (Amgen), Pentoxifylline (Sanofi-Aventis), or NaCl (sham). MRI, Histological (Masson's thricromic), immunofluorescent (CD45 and Collagen VI antibodies, and Lectin from Bandeiraera Simplicifolia), Western blot (sTNFR-I, TNF-β, Phosphorylated-nuclear factor k (NFkBp65), and Collagen VI), SILAC-base mass spectrometry, cytokine arrays, Mission shRNA system (NM_011609.2-1538s1c1, NM_011609.2-996s1c1, and NM_011609.2-1652s1c1), and survival analysis were performed. Our results show that administration of BM-MASCs to MCP-1 mice significantly reduced cardiac accumulation of infiltrating cells and fibrosis, improved capillary density and function, and extended lifespan. Comprehensive analysis of the secretome of MASCs unveiled the release of soluble tumor necrosis factor receptor I (sTNFR-I), which significantly suppressed activation of the NFκBp65 signaling pathway in MCP-1 hearts in vivo. Administration of TNFRI-knock-down BM-MASCs yielded no positive effects demonstrating the requirement of sTNFR-I for BM-MASCs-mediated improvement of inflammatory dilative cardiomyopathy. Substitution of BM-MASCs by recombinant soluble TNFR recapitulated several effects of BM-MASCs including lifespan expansion. We conclude that BM-MASCs suppress local inflammatory processes by release of numerous signaling molecules including sTNFR-I, which makes them useful tools for various clinical applications.
Abstract 17103: VEGF-Mimicking Nanostructures for Ischemic Tissue Repair
Authors: Jörn Tongers, Matthew J Webber, Christina J Newcomb, Johann Bauersachs, Samuel I Stupp, Douglas W Losordo
Journal: Circulation (2011)

Purpose: Repair of ischemic tissue remains an unsolved goal. Current strategies aim to enhance perfusion and, thereby, overcome dysfunction of ischemic tissue. Neovascularization can be achieved via pro-angiogenic agents that enhance sprouting from preexisting vessels (angiogenesis). Due to practical limitations, therapeutic angiogenesis has not shown convincing results in patients. Advances in bionanotechnology, however, enable the development of specific biomaterials to therapeutically improve recovery. Methods/Results: We chose the self-assembling peptide amphiphile (PA) nanofiber platform to design a pro-angiogenic nanofiber that mimics the activity of a pro-angiogenic factor VEGF (VEGF-PA) to enhance angiogenesis. Incubation of human umbilical vein endothelial cells (HUVECs) with VEGF-PA induced cellular functions important for angiogenesis: Compared to untreated control cells, HUVECs treated with VEGF-PA were more resistant to serum-starvation (Annexin staining: VEGF-PA 10±3%, control 32±3, n=6, P&lt;0.001), more mitogenic (CyQuant proliferation assay: VEGF-PA 137±2%, control 100±1%, n=8, P&lt;0.001), and migrated better (scratch assay, reduction of denuded area: VEGF-PA 69±4, control 25±13%, n=6, P&lt;0.05). In a chicken embryo angiogenesis assay, VEGF-PA showed a substantial pro-angiogenic activity (VEGF-PA 229±19%, saline 132±5%, n=16, P&lt;0.001). Local injection of VEGF-PA enhanced limb recovery after surgical hind-limb ischemia in 8-week-old, male FVB/N mice. At day 28, VEGF-PA treated animals showed better perfusion (laser Doppler, ischemic/non-ischemic limb ratio: VEGF-PA 0.7±0.1, saline 0.5±0.1, P&lt;0.05), less tissue damage (score: VEGF-PA 4.2±0.2, saline 3.5±0.2, P&lt;0.05), and better motor function (score: VEGF-PA 4.2±0.2, saline 3.4±0.2, P&lt;0.01) of the ischemic limb. Better recovery after VEGF-PA treatment is associated with more CD31+ capillaries in the ischemic muscle (VEGF-PA 1582±76/mm2, saline 93±53/mm2, P&lt;0.001). Conclusion: Self-assembling, pro-angiogenic PA nanofibers mimicking VEGF enhance ischemic tissue repair and thereby constitute a novel therapeutic alternate to overcome practical limitations in therapeutic angiogenesis.
Methadone maintenance outcome as a function of detoxification phobia
Authors: J B Milby, A A Hohmann, M Gentile, N Huggins, M K Sims, A T McLellan, G Woody, N Haas
Journal: American Journal of Psychiatry (1994)

Methadone maintenance outcome as a function of detoxification phobia was examined.Opiate addicts (N = 271) in a 1983 random sample of methadone maintenance patients from three diverse populations were studied. Subjects from an individually assessed follow-up sample (N = 102) were compared on detoxification phobia. Logistic regression analysis yielded best predictors of the phobia.Phobic patients were more likely to be white, female, and abstinent; to have had fewer detoxification attempts and longer periods on maintenance; to show persistence of the phobia; to meet diagnostic criteria for depressive or anxiety disorders; and to have Addiction Severity Index scores above the 75th percentile for psychological problems.Detoxification phobia has a complex relationship to methadone maintenance outcome. It is associated with greater abstinence for patients in methadone maintenance treatment. However, for rehabilitated phobic patients it presents a barrier to successful detoxification and a drug-free adjustment that is often associated with other psychopathology but could be ameliorated by targeted assessment and treatment.
Abstract 860: Alteration In Blood Pressure Monitoring Technique Impacts Hypertension Treatment
Authors: Gretchen M Ray, Joe R Anderson, James J Nawarskas
Journal: Circulation (2008)

Objectives : Our study investigated the hypothesis that current methods of blood pressure (BP) assessment in an ambulatory clinic result in significantly different BP measurements than those obtained by following the American Heart Association (AHA) recommendations as well as the hypothesis that these BP differences result in treatment variation. Methods: This was a randomized, cross-over study in 40 patients with hypertension presenting to the UNMH Adult Internal Medicine Clinic. BP was measured in all patients in random order by the clinic staff using the traditional triage method and by the Principal Investigator using the AHA-recommended method. Trained observers documented BP techniques used. Two complete patient profiles were constructed for each patient one with the AHA BP and one with the triage BP. A panel of blinded providers including internists, a cardiologist, and a clinical pharmacist was asked to provide hypertensive treatment recommendations for each profile. Results: Only DBP differed significantly (77.6 mmHg ± 11.9 vs. 80.4 mmHg ± 10.5; p=0.02) between the triage and AHA methods, respectively. However, individual BP results varied greatly between the two methods. SBP readings differed by ≥5 mmHg in either direction for 68% of patients while 78% of patient’s DBP readings differed by ≥2 mmHg in either direction. Overall, 65% of patients were not at their goal BP when measured with the AHA method compared to 52% with the triage method (p&lt;0.001). Multiple technical errors were seen during the triage method that likely accounted for the variation. Significant differences in treatment between profiles existed. The number of patients with treatment variations between their two profiles ranged from 13% to 23% (p&lt;0.01 for all providers). Kappa scores indicated moderate to substantial clinical agreement between the physicians but only slight agreement between the pharmacist and physicians. Conclusions: When comparing the two methods of BP measurement, clinically significant differences were observed in a large percentage of patients. This difference significantly impacted hypertension treatment recommendations. Inaccurate BP assessment may lead to inappropriate treatment of hypertension.
Long-Term Follow-up of a Phase 1 Study of Ponatinib in Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML)
Authors: Moshe Talpaz, Jorge E. Cortes, Hagop Kantarjian, Neil P. Shah, Dale Bixby, Ian Flinn, Thomas O'Hare, Simin Hu, Victor M. Rivera, Tim Clackson, Christopher D. Turner, Frank G. Haluska, Brian J. Druker, Michael W. Deininger, Michael J. Mauro
Journal: Blood (2014)
Comorbid association of autism and schizophrenia
Authors: F R Volkmar, D J Cohen
Journal: American Journal of Psychiatry (1991)

In the last several decades, considerable evidence has suggested that autism and schizophrenia are unrelated. However, recent reports have suggested that individuals with autism may be at greater risk for schizophrenia and that the conditions may be more closely related than generally believed.The authors examined detailed case records of 163 adolescents and adults with well-documented histories of autism. These cases included 139 males and 24 females.Only one individual had an unequivocal history of schizophrenia.If the present study group is taken to be representative, it appears that the frequency of schizophrenia among autistic patients (0.6%) is roughly comparable to the frequency of schizophrenia in the general population. It does not appear that the two conditions are more commonly observed together than would be expected on a chance basis; therefore, the current (DSM-III-R) approach to dual diagnosis of these conditions appears reasonable.