tbuckley/cabot-search huggingface dataset:
Survey of intensive care of severely head injured patients in the United Kingdom
Authors: D R Jeevaratnam, D K Menon
Journal: BMJ (1996)

To study practice in intensive care of patients with severe head injury in neurosurgical referral centres in United Kingdom.Structured telephone interview of senior nursing staff in intensive care unit of adult neurosurgical referral centre.39 intensive care units in hospitals that accepted acute head injuries for specialist neurosurgical management, identified from Medical Directory and information from professional bodies.Details of organisation and administration of intensive care and patterns of monitoring and treatment for patients admitted with severe head injury.Patients were managed in specialist neurosurgical intensive care units in 21 of the centres and in general intensive care units in 18. Their intensive care was coordinated by an anaesthetist in 25 units and by a neurosurgeon in 12. Annual case-load varied between units: 20 received > 100 patients, 12 received 50-100, and seven received 25-49. Monitoring and treatment varied considerably between centres. Invasive arterial pressure monitoring was used routinely in 36 units, but central venous pressure monitoring was routinely used in 24 and intracranial pressure was routinely monitored in only 19. Corticosteroids were used to treat intracranial hypertension in 19 units. Seventeen units routinely aimed for arterial carbon dioxide pressure of 3.3-4.0 kPa, and one unit still used severe hyperventilation to a pressure of < 3.3 kPa.The intensive care of patients with acute head injuries varied widely between the centres surveyed. Rationalisation of the intensive care of severe head injury with the production of widely accepted guidelines ought to improve the quality of care.
Raymond Henry Jones
Authors: S. Emerson, N. Statham
Journal: BMJ (2012)

Raymond Henry Jones (“Ray”) was born in Pontyberem, Carmarthenshire on 27 December 1949, the eldest of two boys. His mother died when he was 7 years old, but as he was exceptionally bright he gained a place at Llandovery College, sponsored by Carmarthenshire County Council, where he excelled not only at his studies but also at rugby and cricket. He became the …
Smokescreen: The Truth Behind the Tobacco Industry Cover-up
Authors: Robert N. Proctor
Journal: JAMA (1996)

On December 15, 1953, in Manhattan's luxurious Plaza Hotel, executives of America's most lucrative tobacco companies sat down to plan a strategy to combat the growing animal and epidemiologic evidence of a tobacco hazard. Cigarette consumption in the United States had suffered its first major decline in decades, falling from 418 billion in 1952 to 384 billion. John Hill of the public relations firm Hill &amp; Knowlton proposed a massive campaign to counter reports of the hazards, and the chief executive officers from Philip Morris, RJ Reynolds, Brown &amp; Williamson, American Tobacco, US Tobacco, and Benson &amp; Hedges gave the go-ahead. The result was the establishment of the Tobacco Industry Research Committee (TIRC), a triumph of deception in the guise of research. In the words of H. Lee Sarokin, a New Jersey judge who reviewed the history of the TIRC for a case in 1988, the organization " 'was nothing but
Enzyme Enhancers for the Treatment of Fabry and Pompe Disease
Authors: Jan Lukas, Anne-Marie Pockrandt, Susanne Seemann, Muhammad Sharif, Franziska Runge, Susann Pohlers, Chaonan Zheng, Anne Gläser, Matthias Beller, Arndt Rolfs, Anne-Katrin Giese
Journal: Molecular Therapy (2014)

Lysosomal storage disorders (LSD) are a group of heterogeneous diseases caused by compromised enzyme function leading to multiple organ failure. Therapeutic approaches involve enzyme replacement (ERT), which is effective for a substantial fraction of patients. However, there are still concerns about a number of issues including tissue penetrance, generation of host antibodies against the therapeutic enzyme, and financial aspects, which render this therapy suboptimal for many cases. Treatment with pharmacological chaperones (PC) was recognized as a possible alternative to ERT, because a great number of mutations do not completely abolish enzyme function, but rather trigger degradation in the endoplasmic reticulum. The theory behind PC is that they can stabilize enzymes with remaining function, avoid degradation and thereby ameliorate disease symptoms. We tested several compounds in order to identify novel small molecules that prevent premature degradation of the mutant lysosomal enzymes α-galactosidase A (for Fabry disease (FD)) and acid α-glucosidase (GAA) (for Pompe disease (PD)). We discovered that the expectorant Ambroxol when used in conjunction with known PC resulted in a significant enhancement of mutant α-galactosidase A and GAA activities. Rosiglitazone was effective on α-galactosidase A either as a monotherapy or when administered in combination with the PC 1-deoxygalactonojirimycin. We therefore propose both drugs as potential enhancers of pharmacological chaperones in FD and PD to improve current treatment strategies.
Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 5 (Nox5) Regulation by Angiotensin II and Endothelin-1 Is Mediated via Calcium/Calmodulin-Dependent, Rac-1-Independent Pathways in Human Endothelial Cells
Authors: Augusto C. Montezano, Dylan Burger, Tamara M. Paravicini, Andreia Z. Chignalia, Hiba Yusuf, Mahmoud Almasri, Ying He, Glaucia E. Callera, Gang He, Karl-Heinz Krause, David Lambeth, Mark T. Quinn, Rhian M. Touyz
Journal: Circulation Research (2010)

Although Nox5 (Nox2 homolog) has been identified in the vasculature, its regulation and functional significance remain unclear.We sought to test whether vasoactive agents regulate Nox5 through Ca(2+)/calmodulin-dependent processes and whether Ca(2+)-sensitive Nox5, associated with Rac-1, generates superoxide (O(2)(*-)) and activates growth and inflammatory responses via mitogen-activated protein kinases in human endothelial cells (ECs).Cultured ECs, exposed to angiotensin II (Ang II) and endothelin (ET)-1 in the absence and presence of diltiazem (Ca(2+) channel blocker), calmidazolium (calmodulin inhibitor), and EHT1864 (Rac-1 inhibitor), were studied. Nox5 was downregulated with small interfering RNA. Ang II and ET-1 increased Nox5 expression (mRNA and protein). Effects were inhibited by actinomycin D and cycloheximide and blunted by diltiazem, calmidazolium and low extracellular Ca(2+) ([Ca(2+)](e)). Ang II and ET-1 activated NADPH oxidase, an effect blocked by low [Ca(2+)](e), but not by EHT1864. Nox5 knockdown abrogated agonist-stimulated O(2)(*-) production and inhibited phosphorylation of extracellular signal-regulated kinase (ERK)1/2, but not p38 MAPK (mitogen-activated protein kinase) or SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase). Nox5 small interfering RNA blunted Ang II-induced, but not ET-1-induced, upregulation of proliferating-cell nuclear antigen and vascular cell adhesion molecule-1, important in growth and inflammation.Human ECs possess functionally active Nox5, regulated by Ang II and ET-1 through Ca(2+)/calmodulin-dependent, Rac-1-independent mechanisms. Nox5 activation by Ang II and ET-1 induces ROS generation and ERK1/2 phosphorylation. Nox5 is involved in ERK1/2-regulated growth and inflammatory signaling by Ang II but not by ET-1. We elucidate novel mechanisms whereby vasoactive peptides regulate Nox5 in human ECs and demonstrate differential Nox5-mediated functional responses by Ang II and ET-1. Such phenomena link Ca(2+)/calmodulin to Nox5 signaling, potentially important in the regulation of endothelial function by Ang II and ET-1.
Malignant Sadness: The Anatomy of Depression
Authors: T L Chambers
Journal: Journal of the Royal Society of Medicine (2002)

A pastime of doctors is to rate the diseases they would wish not to have. Depression invariably comes high on the list. A colleague of mine, prone to recurrent episodes, remarked on the special bitterness of being a doctor-victim; and, in Malignant Sadness, Professor Wolpert (a research biologist) acknowledges that the burden on physicians is particularly high. The book, originally published in 1999 and now reissued with a new introduction, is derived from his own experience of depression. Responses to his personal revelations, in newspapers and in a television series, indicated that many people still hesitate to seek treatment because of the stigma attached to this condition. Wolpert himself, before his severest breakdown, subscribed to the ‘sock’ school of psychiatry—pull them up.
Pulmonary perfusion abnormalities and ventilation-perfusion imbalance in children after total repair of tetralogy of Fallot.
Authors: P O Alderson, S Boonvisut, R C McKnight, A F Hartman
Journal: Circulation (1976)

The pulmonary perfusion of 25 children who had total surgical correction of tetralogy of Fallot was evaluated by radionuclide perfusion scans. In addition, 18 had 133Xe ventilation studies. Eighteen of the children previously had palliative systemic-pulmonary shunts; 14 had aortic-pulmonary shunts (Waterston or Potts-Smith) and four had Blalock-Taussig shunts. Seven children had single stage total corrections. An asymmetric perfusion pattern was found in 13 of 18 children who previously had systemic-pulmonary shunts, including 12 of 14 with previous aortic-pulmonary shunts (P less than 0.05). The most common finding was relative hypoperfusion of the lung which had received the palliative shunt (P less than 0.001). The distribution of ventilation remained relatively symmetric, even when perfusion was markedly abnormal, and this resulted in ventilation-perfusion imbalance in several patients. Asymmetric perfusion was significantly less common in patients who had undergone single stage corrections (P less than 0.05). The findings document the frequent occurrence of residual abnormalities of pulmonary perfusion and ventilation-perfusion imbalance in patients who have palliative aortic-pulmonary shunts prior to total repair, and support the position that single stage correction is preferable to aortic-pulmonary shunting in the surgical management of tetralogy of Fallot.
RETRACTED: Methylation Mediated Silencing of MicroRNA-1 Gene and Its Role in Hepatocellular Carcinogenesis
Authors: Jharna Datta, Huban Kutay, Mohd W. Nasser, Gerard J. Nuovo, Bo Wang, Sarmila Majumder, Chang-Gong Liu, Stefano Volinia, Carlo M. Croce, Thomas D. Schmittgen, Kalpana Ghoshal, Samson T. Jacob
Journal: Cancer Research (2008)

Abstract MicroRNAs (miR) are a class of small (∼21 nucleotide) noncoding RNAs that, in general, negatively regulate gene expression. Some miRs harboring CGIs undergo methylation-mediated silencing, a characteristic of many tumor suppressor genes. To identify such miRs in liver cancer, the miRNA expression profile was analyzed in hepatocellular carcinoma (HCC) cell lines treated with 5-azacytidine (DNA hypomethylating agent) and/or trichostatin A (histone deacetylase inhibitor). The results showed that these epigenetic drugs differentially regulate expression of a few miRs, particularly miR-1-1, in HCC cells. The CGI spanning exon 1 and intron 1 of miR-1-1 was methylated in HCC cell lines and in primary human HCCs but not in matching liver tissues. The miR-1-1 gene was hypomethylated and activated in DNMT1−/− HCT 116 cells but not in DNMT3B null cells, indicating a key role for DNMT1 in its methylation. miR-1 expression was also markedly reduced in primary human hepatocellular carcinomas compared with matching normal liver tissues. Ectopic expression of miR-1 in HCC cells inhibited cell growth and reduced replication potential and clonogenic survival. The expression of FoxP1 and MET harboring three and two miR-1 cognate sites, respectively, in their respective 3′-untranslated regions, was markedly reduced by ectopic miR-1. Up-regulation of several miR-1 targets including FoxP1, MET, and HDAC4 in primary human HCCs and down-regulation of their expression in 5-AzaC–treated HCC cells suggest their role in hepatocarcinogenesis. The inhibition of cell cycle progression and induction of apoptosis after re-expression of miR-1 are some of the mechanisms by which DNA hypomethylating agents suppress hepatocarcinoma cell growth. [Cancer Res 2008;68(13):5049–58]
Hyperbaric Oxygen Therapy
Authors: LAWRENCE W. RAYMOND
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 July 1973Hyperbaric Oxygen TherapyLAWRENCE W. RAYMOND, M.D.LAWRENCE W. RAYMOND, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-1-138_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The Glausers have presented a reasonable estimate of the amount of tissue that can be expected to be saved by hyperbaric oxygen therapy after acute coronary arterial occlusion (Ann Intern Med78:77-80, 1973). Their conclusion is, however, unwarranted, for they have addressed themselves only to a single aspect of a complex process. It is clear that cardiac arrhythmias and shock can accompany infarctions related to focal large-vessel or diffuse small-vessel occlusion. Both complications have a high mortality. Thus the conclusion that hyperbaric oxygen is of no value in large-vessel occlusion—although it may ultimately prove true—is not adequately...References1. CHARDACKGAGEFEDERICO WAA: Reduction by hyperbaric oxygenation of the mortality from ventricular fibrillation after coronary artery ligation. Circ Res 15:497-502, 1964 CrossrefMedlineGoogle Scholar2. PIFARREYOKOYAMAILANO RTA: The role of controlled ventilation in the treatment of acute myocardial infarction. J Thorac Cardiovasc Surg 53:781-788, 1967 CrossrefMedlineGoogle Scholar3. PIFARRERAGHUNATHVANECKO RTR: Effect of oxygen and helium mixtures on ventricular fibrillation. J Thorac Cardiovasc Surg 60:648-652, 1970 CrossrefMedlineGoogle Scholar4. RAYMONDWEISKOPFHALSEY LRM: Possible mechanism for the antiarrhythmic effect of helium in anesthetized dogs. Science 176:1250-1252, 1972 CrossrefMedlineGoogle Scholar5. ASHFIELDGAVEY RC: Severe acute myocardial infarction treated with hyperbaric oxygen—report on 40 patients. Postgrad Med J 45:648-654, 1969 CrossrefMedlineGoogle Scholar1. CHARDACKGAGEFEDERICO WAA: Reduction by hyperbaric oxygenation of the mortality from ventricular fibrillation following coronary artery ligation. Circ Res 15:497-502, 1964 CrossrefMedlineGoogle Scholar2. HOLLOWAYWHALENSALTZMAN DRH: Hyperbaric oxygenation in the treatment of acute coronary artery embolization in dogs. J Lab Clin Med 66:596-603, 1965 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1973Volume 79, Issue 1Page: 138-139KeywordsArrhythmiaHyperbaric oxygenInfarctionMortalityShock Issue Published: 1 July 1973 PDF DownloadLoading ...
Metabolic Memory in the Autonomic Neuropathy of Diabetes
Authors: Nishi Chaturvedi
Journal: Circulation (2009)

M etabolic memory, the concept that historical glycemic control is a major determinant of diabetes complications, is of considerable interest not only to those involved in the care of people with diabetes mellitus but also to a wider audience, those wishing to understand the pathogenesis of hyperglycemia-related target organ damage.2][3] An article in this issue of Circulation from the DCCT/EDIC Research Group demonstrates the same phenomenon for cardiac autonomic neuropathy (CAN). 4In the DCCT, intensive glycemic control over an average of 6.5 years achieved a marked reduction in hemoglobin A 1c , 1.7% lower than that achieved on conventional therapy, and a reduction in CAN incidence of 53%. 5 At the termination of DCCT, all participants were encouraged to adopt intensive glycemic control such that 5 years after DCCT termination, there was no significant difference in hemoglobin A 1c between the originally randomized groups.At 13 to 14 years of follow up, CAN incidence subsequent to DCCT termination in those initially randomized to intensive control was reduced by a third compared with those randomized to conventional therapy, even though glycemic control had been identical in these groups for decade before the CAN assessment.Statistical adjustment for historical glycemic control, specifically that achieved during the DCCT itself, abolished the group difference in CAN, supporting the assertion that metabolic memory explained the persistent lower risk of CAN in those originally randomized to intensive glycemic control.
REMARKS ON APPENDICITIS.
Authors: J. H. CARSTENS
Journal: JAMA (1895)

Appendicitis is talked of and written about a great deal, and when I go around with my professional friends who practice in the small cities and villages, they all say: "Appendicitis is a great fad. We seldom see a case; why is it that you see so much and operate on so many, while we rarely see a case?" Some of them even, who look at everything with a pessimistic eye, say that many cases are operated upon and reported that are not cases of appendicitis at all. Some of them have quite a large practice and only once in a while do they see a case that they call appendicitis, and how others can see dozens and hundreds a year is utterly beyond their comprehension. But the solution is very easy; from what I am able to find out, from the number of cases of appendicitis occurring in the
Antiglomerular basement membrane antibody mediated disease in the British Isles 1980-4.
Authors: C O Savage, C D Pusey, C Bowman, A J Rees, C M Lockwood
Journal: BMJ (1986)

Clinical and pathological data on 71 patients from throughout the British Isles who developed antiglomerular basement membrane antibody mediated nephritis in the period 1980-4 were studied. Two principle patterns of disease were recognised: young men presenting in their 20s with Goodpasture's syndrome (glomerulonephritis and lung haemorrhage) and women presenting in their 60s with glomerulonephritis alone. The effect of treatment on prognosis of a total of 108 patients was also reviewed (the 71 patients plus patients seen before 1980 at Hammersmith Hospital). Treatment with prednisolone, cytotoxic drugs, and plasma exchange hastened the time to clearance of autoantibody and improved the outlook of patients who were not dependent on dialysis and those with lung haemorrhage.
505 Conversion of liver transplant recipients with hepatitis B virus from hepatitis B immune globulin (HBIG) and lamivudine (LAM) to adefovir dipivoxil (ADV) and LAM
Authors: G.W. Neff, V.C. Zacharias, M. Alonzo, N. Kenner, E. Weber, T.E. Kaiser, K. Safdar, E. Rideman, M. Thomas, J. Martin, S. Rudich, A. Tevar, J. Buell
Journal: Journal of Hepatology (2006)
Does Stringent Restrictive Annuloplasty for Functional Mitral Regurgitation Cause Functional Mitral Stenosis and Pulmonary Hypertension?
Authors: Satoshi Kainuma, Kazuhiro Taniguchi, Takashi Daimon, Taichi Sakaguchi, Toshihiro Funatsu, Haruhiko Kondoh, Shigeru Miyagawa, Koji Takeda, Yasuhiro Shudo, Takafumi Masai, Shinichi Fujita, Masami Nishino, Yoshiki Sawa
Journal: Circulation (2011)

Background— It remains controversial whether restrictive mitral annuloplasty (RMA) for functional mitral regurgitation (MR) can induce functional mitral stenosis (MS) that may cause postoperative residual pulmonary hypertension (PH). Methods and Results— One hundred eight patients with left ventricular (LV) dysfunction and severe MR underwent RMA with stringent downsizing of the mitral annulus. Systolic pulmonary artery pressure (PAP) and mitral valve performance variables were determined by Doppler echocardiography prospectively and 1 month after RMA. Fifty-eight patients underwent postoperative hemodynamic measurements. Postoperative echocardiography showed a mean pressure half-time of 92±14 ms, a transmitral mean gradient of 2.9±1.1 mm Hg, and a mitral valve effective orifice area of 2.4±0.4 cm 2 , consistent with functional MS. Doppler-derived systolic PAP was 32±8 mm Hg, which correlated weakly with the transmitral mean gradient (ρ=0.23, P =0.02). Postoperative cardiac catheterization also showed significant improvements in LV volume and systolic function, pulmonary capillary wedge pressure, cardiac index, and systolic PAP; the latter was associated with LV end-diastolic pressure [standardized partial regression coefficient (SPRC)=0.51], pulmonary vascular resistance (SPRC=0.47), cardiac index (SPRC=0.37), and transmitral pressure gradient (SPRC=0.20). In a multivariate Cox proportional hazard model, postoperative PH (systolic PAP &gt;40 mm Hg), but not mitral valve performance variables, was strongly associated with adverse cardiac events. Conclusions— RMA for functional MR resulted in varying degrees of functional MS. However, our data were more consistent with the residual PH being caused by LV dysfunction and pulmonary vascular disease than by the functional MS. The residual PH, not functional MS, was the major predictor of post-RMA adverse cardiac events.
Clinico-pathological, immunological and virological characteristics of patients transplanted for cryptogenic cirrhosis
Authors: Jean-Charles Duclos-Vallee, Catherine Johanet, Anne-Marie Roque, Michele Gigou, Cyrille Feray, Jean-Francois Emile, Mylene Sebagh, Henri Bismuth, Didier Samuel, Catherine Guettier
Journal: Journal of Hepatology (2002)