tbuckley/cabot-search huggingface dataset:
THE MECHANISM OF FRACTURES OF THE VERTEBRAL BODIES
Authors: A. M. RECHTMAN
Journal: American Journal of Psychiatry (1940)

1. A study of the anatomy and of the practical considerations of the spine shows that fractures of the vertebral bodies are usual at those areas of the spine that are mechanically weak or exposed to the effects of traumatism. 2. Metrazol acts to cause convulsions attendant with very forcible muscular contractions sufficient to fracture the bodies of the vertebræ in the mid-dorsal region which is anatomically and dynamically vulnerable. The localization differs from the more usual sites of fracture because of a modification of the type of stress and strain peculiar to the muscular contractions caused by metrazol injections and their effects on the anatomy of the parts affected. The degree of injury varies directly with the force of the muscular contractions and inversely with the resistance offered by, or the strength of, the vertebral bodies. The force of the muscular contractions and the energy expended is so great that a convulsion continuing for 90 seconds may exhaust the patient for 8 to 24 hours. 3. The mid-dorsal area of the spine is anatomically vulnerable and fractures occur at this site following metrazol therapy because the site is midway between the forward physiological curves of the cervical area above and the lumbar below. The degree of flexion occurs through an arc sufficiently small to make the mid-dorsal spine the recipient of its greatest effects. The vertebral bodies are here wider anteriorly while the discs are smaller, less resilient and more narrow anteriorly; and the dynamic center of the flexor contracting force of the trunk muscles is at this level. 4. The number of metrazol injections has no relation to the number of vertebral bodies fractured or to the degree of wedging. The extent and degree of injury are rather dependent upon the intensity of the muscular contractions, due to any one particular convulsive treatment, and the strength of the spine to withstand the shock. Undoubtedly if a fracture occurs early in the course of treatment and if treatments continue without the prophylactic measures recommended, increased wedging of the vertebræ may obtain. 5. Rupture of the nucleus pulposus with protrusion into the neural canal is most unusual following fractures of the vertebral body. 6. No practical type of mechanical fixation can prevent injury to the vertebral bodies. 7. Prophylaxis is possible, and the use of spinal anesthesia given prior to the metrazol injections as suggested by Hamsa and Bennett is recommended. 8. If fracture occur, immobilization of the trunk between treatments and reduction of the deformity, if it is present, with fixation in a plaster jacket for six months after the treatments are completed should result in entire healing of the fractures.
Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes
Authors: Nahuel A. Garcia, Javier Moncayo-Arlandi, Pilar Sepulveda, Antonio Diez-Juan
Journal: Cardiovascular Research (2015)

Cardiomyocytes (CMs) and endothelial cells (ECs) have an intimate anatomical relationship, which is essential for maintaining the metabolic requirements of the heart. Little is known about the mechanisms that regulate nutrient flow from ECs to associated CMs, especially in situations of acute stress when local active processes are required to regulate endothelial transport. We examined whether CM-derived exosomes can modulate glucose transport and metabolism in ECs. In conditions of glucose deprivation, CMs increase the synthesis and secretion of exosomes. These exosomes are loaded with functional glucose transporters and glycolytic enzymes, which are internalized by ECs, leading to increased glucose uptake, glycolytic activity, and pyruvate production in recipient cells. These findings establish CM-derived exosomes as key components of the cardio-endothelial communication system which, through intercellular protein complementation, would allow a rapid response from ECs to increase glucose transport and a putative uptake of metabolic fuels from blood to CMs. This CM–EC protein complementation process might have implications for metabolic regulation in health and disease.
Abstract 13853: Biological Action of ABCA1 Ligand Peptide ATI-5261 and its Analogs With Improved Safety Features
Authors: John K Bielicki, Stefanie Bittner, Juveria Tabassum, Anouar Hafiane, Jacques Genest, Salman Azhar, Jan Johansson
Journal: Circulation (2013)

Recent studies have produced apolipoprotein (apo) mimetic peptides that reduce substantial atherosclerosis in animal models when given orally, subcutaneously or intravenously in lipid-free form and composed of L-amino acids. These findings suggest small peptides may represent a viable approach for the treatment of acute coronary syndrome and atherosclerosis in humans. Despite these favorable features, several adverse effects have been noted in preclinical studies, including elevations in blood triglycerides (TG) and cytotoxic responses (ALT, AST and creatine kinase) at high doses. To address these issues, we established a screening paradigm involving >200 analogs of ATI-5261, a novel apoE mimetic peptide and ABCA1 ligand that stimulates cellular cholesterol efflux with high potency. Safety profiles of peptides were evaluated in mice and rats, and anti-atherosclerosis effects in apoE deficient (apoE-/-) mice fed high-fat western-diet (HFWD) for 14 weeks. These studies revealed the TG elevating effects and cytotoxic responses of class A a-helical peptides were governed by a different set of molecular determinants apart from those of ABCA1 mediated cholesterol efflux. A lead peptide (CS6253) emerged with improved safety features that retained the favorable drugability properties (i.e. solubility), potent and selective cholesterol efflux activity via ABCA1 (km= 0.26±0.14 vs. 0.25±0.04 uM for ATI-5261, respectively), and mediated high affinity binding to ABCA1 as well as produced nascent HDL similar to full-length apoA-I. In vivo CS6253 stimulated macrophage specific RCT and reduced (32%) substantial atherosclerosis in apoE-/- mice when administered (SQ or IP) at a dose of 30 mg/kg over 6 weeks. These structure-activity studies from lead optimization of the ATI-5261 peptide series provide new and exciting insights for improving the therapeutic potential of apo mimetic peptides.
p73 and IGF1R Regulate Emergence of Aggressive Cancer Stem–like Features via miR-885-5p Control
Authors: Claudia Meier, Philip Hardtstock, Sophie Joost, Vijay Alla, Brigitte M. Pützer
Journal: Cancer Research (2015)

Abstract Cancer stem–like cells (CSC) have been proposed to promote cancer progression by initiating tumor growth at distant sites, suggesting that stem-like cell features can support metastatic efficiency. Here, we demonstrate that oncogenic DNp73, a dominant-negative variant of the tumor-suppressor p73, confers cancer cells with enhanced stem-like properties. DNp73 overexpression in noninvasive melanoma and lung cancer cells increased anchorage-independent growth and elevated the expression of the pluripotency factors CD133, Nanog, and Oct4. Conversely, DNp73 depletion in metastatic cells downregulated stemness genes, attenuated sphere formation and reduced the tumor-initiating capability of spheroids in tumor xenograft models. Mechanistic investigations indicated that DNp73 acted by attenuating expression of miR-885-5p, a direct regulator of the IGF1 receptor (IGF1R) responsible for stemness marker expression. Modulating this pathway was sufficient to enhance chemosensitivity, overcoming DNp73-mediated drug resistance. Clinically, we established a correlation between low p73 function and high IGF1R/CD133/Nanog/Oct4 levels in melanoma specimens that associated with reduced patient survival. Our work shows how DNp73 promotes cancer stem–like features and provides a mechanistic rationale to target the DNp73–IGF1R cascade as a therapeutic strategy to eradicate CSC. Cancer Res; 76(2); 197–205. ©2015 AACR.
Autoantibodies to citrullinated proteins may induce joint pain independent of inflammation
Authors: Gustaf Wigerblad, Duygu B Bas, Cátia Fernades-Cerqueira, Akilan Krishnamurthy, Kutty Selva Nandakumar, Katarzyna Rogoz, Jungo Kato, Katalin Sandor, Jie Su, Juan Miguel Jimenez–Andrade, Anja Finn, Alex Bersellini Farinotti, Khaled Amara, Karin Lundberg, Rikard Holmdahl, Per-Johan Jakobsson, Vivianne Malmström, Anca I Catrina, Lars Klareskog, Camilla I Svensson
Journal: Annals of the Rheumatic Diseases (2015)

Objective An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation. Methods Antibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin. Results Mice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin. Conclusions The data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation.
Unusual Forms of Insulin Resistance
Authors: S I Taylor, D Accili, A Cama, E Imano, H Kadowaki, T Kadowaki
Journal: Annual Review of Medicine (1991)

Insulin resistance is an important feature in the pathogenesis of noninsulin-dependent diabetes mellitus. Some rare patients have syndromes associated with a severe form of insulin resistance, usually involving acanthosis nigricans and, in premenopausal females, hyperandrogenism. This review discusses two of the causes of insulin resistance: mutations in the insulin receptor gene and autoantibodies directed against the insulin receptor.
Instrumental psychosis: the Good Soldier Svejk syndrome
Authors: Peter Tyrer, Nicholas Babidge, Jo Emmanuel, Nishi Yarger, Maya Ranger
Journal: Journal of the Royal Society of Medicine (2001)

The possession of severe mental illness, mainly schizophrenia and affective psychosis, may be perceived in positive terms. We have identified a group of patients, most of them with a history of previous psychotic disorder, who present with deliberately created symptoms and behaviour, and who are defined as having instrumental psychosis. Because most such patients have had a psychotic disorder in the past the symptoms are very like those of a real psychosis. A parallel is drawn with the fictional anti-hero of the Czech nation, the Good Soldier Svejk, who demonstrated both real and instrumental psychosis. A rating scale, the 'pseudopsychosis inventory', was devised to identify the main components of this disorder and was applied in 15 consecutive patients presenting with putative psychotic disorders in whom assessment could be made by two raters within five days. The inter-rater reliability of the items of the scale was good (intra-class correlation coefficient 0.68). An epidemiological study with this scale in 45 patients with a putative psychotic disorder suggested the presence of instrumental psychosis in 2.
Static and dynamic prognostic factors for hepatitis-B-related acute-on-chronic liver failure
Authors: Jung Min Ha, Won Sohn, Ju Yeon Cho, Jeung Hui Pyo, Kyu Choi, Dong Hyun Sinn, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Chul Koh, Seung Woon Paik, Byung Chul Yoo, Yong-Han Paik
Journal: Clinical and Molecular Hepatology (2015)

Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission.Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals.A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (≥28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (≥grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016).Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
Population tailored modification of tuberculosis specific interferon-gamma release assay
Authors: Kata Horvati, Szilvia Bősze, Hannah P. Gideon, Bernadett Bacsa, Tamás G. Szabó, Rene Goliath, Molebogeng X. Rangaka, Ferenc Hudecz, Robert J. Wilkinson, Katalin A. Wilkinson
Journal: Journal of Infection (2015)
Cisplatin-based chemotherapy in advanced basal and squamous cell carcinomas of the skin: results in 28 patients including 13 patients receiving multimodality therapy.
Authors: T H Guthrie, E S Porubsky, M N Luxenberg, K J Shah, K L Wurtz, P R Watson
Journal: Journal of Clinical Oncology (1990)

This study reports the results of cisplatin (CDDP)-based chemotherapy (CT) as sole therapy and as neoadjuvant (NA) therapy in 28 consecutive patients (pts) with advanced basal cell (BC) and squamous cell (SC) cancers of the skin. CT in 24 pts consisted of CDDP 75 mgm/m2 and doxorubicin (Dox) 50 mg/m2 intravenously (IV) every 3 weeks with Dox being omitted in four pts due to severe preexisting cardiac disease. Thirteen of the 28 pts received CT in the NA setting, five before surgery and eight before radiation therapy (RT). Response rates to CT were complete remission (CR) in eight of 28 (28%) pts, partial remission (PR) in 11 of 28 (40%) for an overall response rate of 68%. Thirteen pts received a second treatment modality with five of 13 pts having a CR to CT alone before the second modality and seven converting to CR postsecond modality for a total CR rate of 12 of 13 (92%) in the multimodality group. Duration of responses in the CT-only group ranged from 4 to 82 months; however, only two patients remain in remission in this group. Of the twelve CRs from the multimodality therapy group, 11 of 12 (91%) pts remain in CR with duration of response ranging from 3 to 81 months. Toxicities were manageable, with no toxic deaths and only five pts stopped CT secondary to side effects. This study suggests the combination of CDDP and Dox is highly effective in BC and SC cancers of the skin and by itself can produce long unmaintained remissions, but when combined with a second modality of therapy, it is capable of producing not only long unmaintained CRs but probable cures in the majority of pts.
Immunotherapy for Lung Cancer
Authors: Rebecca Voelker
Journal: JAMA (2015)

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Abstract 16530: Post-exercise Flow-mediated Dilation is augmented in Highly Trained Female Athletes
Authors: Daniela K Andaku, Bruno Archiza, Flavia C Caruso, Katiany T Zangrando, Humberto Lanzotti, André C Amaral, José Carlos Bonjorno Jr, Cláudio R de Oliveira, Shane A Phillips, Ross Arena, Audrey Borghi-Silva
Journal: Circulation (2015)

Background: Recent evidence has indicated a ceiling to the benefits of exercise training that, if chronically surpassed, may have a negative effect on cardiac function. Conversely, improvements in peripheral arterial function may respond positively to chronic high volume training. Recent studies have shown that flow-mediated dilation (FMD) is decreased immediately after maximal exercise in sedentary subjects and is unaltered in subjects who participate in moderate volume exercise. We investigated the acute effects of maximal exercise on vascular function of elite female athletes with a high-volume training history. Methods: Fifteen elite female soccer players (mean age: 22.1 ± 4.4 years; BMI: 20.76 ± 1.75 kg/m2), with a high volume/intensity training history (4-6 hours per day) were evaluated. Subjects underwent maximal cardiopulmonary exercise testing (CPX) on a treadmill (VO2max 41.1 ± 3.9 mLO2•kg-1•min-1). Brachial artery FMD was determined using high-resolution ultrasound before and immediately after CPX. Flow velocity were measured at baseline (BSL) and during reactive hyperemia (RH) both prior to and following exercise. Results: Brachial artery diameter increased during RH before (3.42 ± 0.38mm vs. 3.03 ± 0.28mm, p&lt;0.001) and after CPX (3.61 ± 0.44mm vs. 3.10 ± 0.37mm, p&lt;0.001). Importantly, FMD was increased following CPX compared to BSL (16.86 ± 9.04% vs. 12.95 ± 7.03%, p=0.027). There was significant increase in peak flow velocity during RH before (135.28 ± 42.19cm/s vs. 79.19 ± 28.14cm/s, p=0.001) and after CPX (139.15 ± 41.07cm/s vs. 87.64 ± 21.23cm/s, p&lt;0.001) (Table). Conclusion: The results of the current study indicate that arterial function is improved following acute aerobic exercise in elite female athletes with a chronic high volume training history. These findings deviate from the emerging literature suggesting chronic high volume training may be detrimental to cardiovascular function in the long term.
Predictors of Long-Term Healthy Arterial Aging
Authors: Seamus P. Whelton, Michael G. Silverman, John W. McEvoy, Matthew J. Budoff, Ron Blankstein, John Eng, Roger S. Blumenthal, Moyses Szklo, Khurram Nasir, Michael J. Blaha
Journal: JACC. Cardiovascular imaging (2015)
Screening for Cervical Cancer: Review of Administrative Arrangements
Authors: M J Pye
Journal: Journal of the Royal Society of Medicine (1988)

In 1980 a working party was established in Cambridge Health District to review the administrative arrangements for cervical cytology recall using the National Health Service Central Register at Southport. As a result of a number of surveys and ad hoc enquiries it was decided not to continue with the central recall scheme (which was subsequently withdrawn) and not to replace it with any formal centralized local scheme. The decision was based on the apparent failure of the central scheme, the effectiveness of informal systems already in operation locally, and the need to place cervical cancer amongst competing priorities for prevention.
Are there three main subgroups within the patellofemoral pain population? A detailed characterisation study of 127 patients to help develop targeted intervention (TIPPs)
Authors: James Selfe, Jessie Janssen, Michael Callaghan, Erik Witvrouw, Chris Sutton, Jim Richards, Maria Stokes, Denis Martin, John Dixon, Russell Hogarth, Vasilios Baltzopoulos, Elizabeth Ritchie, Nigel Arden, Paola Dey
Journal: British Journal of Sports Medicine (2016)

Background Current multimodal approaches for the management of non-specific patellofemoral pain are not optimal, however, targeted intervention for subgroups could improve patient outcomes. This study explores whether subgrouping of non-specific patellofemoral pain patients, using a series of low cost simple clinical tests, is possible. Method The exclusivity and clinical importance of potential subgroups was assessed by applying à priori test thresholds (1 SD) from seven clinical tests in a sample of adult patients with non-specific patellofemoral pain. Hierarchical clustering and latent profile analysis, were used to gain additional insights into subgroups using data from the same clinical tests. Results 130 participants were recruited, 127 had complete data: 84 (66%) female, mean age 26 years (SD 5.7) and mean body mass index 25.4 (SD 5.83), median (IQR) time between onset of pain and assessment was 24 (7–60) months. Potential subgroups defined by the à priori test thresholds were not mutually exclusive and patients frequently fell into multiple subgroups. Using hierarchical clustering and latent profile analysis three subgroups were identified using 6 of the 7 clinical tests. These subgroups were given the following nomenclature: (1) ‘strong’, (2) ‘weak and tighter’ and (3) ‘weak and pronated foot’. Conclusions We conclude that three subgroups of patellofemoral patients may exist based on the results of six clinical tests which are feasible to perform in routine clinical practice. Further research is needed to validate these findings in other data sets and, if supported by external validation, to see if targeted interventions for these subgroups improve patient outcomes.