tbuckley/cabot-search huggingface dataset:
Location of Diastolic Potentials in Reentrant Circuits Causing Sustained Ventricular Tachycardia in the Infarcted Canine Heart
Authors: Candido Cabo, Heiko Schmitt, Gregory Masters, James Coromilas, Andrew L. Wit, Melvin M. Scheinman
Journal: Circulation (1998)

The complete reentrant circuit for ablation of reentrant ventricular tachycardia (VT) in humans can rarely be localized by mapping. As a result, surrogate markers, such as diastolic electrical activity, subsequently confirmed by entrainment, have been used. However, ablation at those sites has had variable efficacy. The reasons for this variability are not clear.We correlated activation maps of reentrant circuits in the epicardial border zone of 4-day old infarcted dog hearts with the corresponding ECGs for 45 VTs to determine the regions of the reentrant circuits activated during diastole. In VTs with a figure-8 reentrant pattern, the center point of the central common pathway, the part of the circuit critical for the maintenance of reentry, was activated in early diastole in 32 of 35 VTs (91.4%), in late diastole in 1 (2.9%), and in systole in 2 (5.7%). Regions outside the circuit were rarely activated in diastole. In 10 VTs, the reentrant circuit was characterized by a single reentrant loop. In these circuits, no one region was predicted to be critical for maintenance of reentry, and a segment of the circuits was activated during diastole. However, regions peripheral to the circuit were also activated during diastole.The pattern of reentrant activation determines the specificity of diastolic activity for locating critical sites for ablation of VT.
CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection
Authors: Kevin D. Pavelko, Michael J. Hansen, Larry R. Pease
Journal: Cancer Research (2009)

Abstract Vaccine strategies for cancer immunotherapy have focused on peptide ligands with high affinity for MHC class I. Largely, these vaccines have not been therapeutic. We have examined the peptide specificity of a strongly protective T-cell response that eradicates established B16 melanoma and find that the recognized epitope is generated by a low-affinity MHC class I ligand from tyrosinase-related protein 1 (TRP1). Cytotoxic T-cell responses are induced against TRP1222-229 by several vaccination schemes using a Toll-like receptor agonist, T regulatory cell depletion, or the immune modulator B7-DCXAb to drive immunity. TRP1222 CTL are generated from multiple antigen sources, including antigens expressed by tumors growing in situ, tumor cell lysates, and peptide vaccines. The key finding in this study is that protection from freshly implanted or established B16 tumors is primarily mediated by TRP1222-specific CTL and not by CTL specific for more traditional melanoma antigens such as TRP2 or gp100. This finding challenges the assumption that the optimal peptide antigens for cancer vaccines are high-affinity MHC ligands. We propose that when administered appropriately, native low-affinity MHC ligands are optimal inducers of immunotherapeutic CTL. [Cancer Res 2009;69(7):3114–20]
The Language of Case Histories
Authors: Xavier Bosch
Journal: Annals of Internal Medicine (1998)

Letters15 May 1998The Language of Case HistoriesXavier Bosch, MD, PhDXavier Bosch, MD, PhDHospital Casa Maternitat; 08028 Barcelona, SpainSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-10-199805150-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I agree with most aspects of Dr. Donnelly's essay on questionable language of medical case histories [1]. Dr. Donnelly wonders why the seven practices (or maladies) continue despite extensive criticism. He cites two main reasons: that sickness is considered a matter of disordered biology and, accordingly, that physicians adopt the viewpoint and methods of natural scientists. Thus, he states that a conventional, biomedically oriented history of present illness just reflects the facts and that more attention should be paid to the patient's personal experience. In discussing the remedies to correct the language maladies, he suggests that a ...References1. Donnelly WJ. The language of medical case histories. Ann Intern Med. 1997; 127:1045-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: Hospital Casa Maternitat; 08028 Barcelona, Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 May 1998Volume 128, Issue 10Page: 876-877KeywordsDo not resuscitate ordersEmotionsFearHospitalizationsOutpatient clinicsOutpatientsScientists Issue Published: 15 May 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Tracheal gas insufflation-pressure control versus volume control ventilation. A lung model study.
Authors: H Imanaka, R M Kacmarek, R Ritz, D Hess
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Tracheal gas insufflation (TGI) has been recommended as an adjunct to mechanical ventilation in the presence of elevated Pa CO2. Based on our initial clinical experience with continuous flow TGI and pressure control ventilation (PCV), we were concerned about elevation in peak airway pressure as TGI was applied. In a lung model, we evaluated the effects of continuous flow TGI during both PCV and volume control ventilation (VCV). A single compartment lung model was configured with an artificial trachea into which an 8-mm endotracheal tube was positioned. TGI was established with a 16-G catheter positioned 2 cm beyond the tip of the endotracheal tube. Ventilation was provided by a Puritan-Bennett 7200ae ventilator with PCV 20 cm H2O or VCV with a tidal volume (VTt) similar to that with PCV. A rate of 15 breaths/min and PEEP of 10 cm H2O were used throughout. Inspiratory times (TI) of 1.0, 1.5, 2.0, and 2.5 s were used with TGI of 0, 4, 8, and 12 L/min. Lung model compliance (ml/cm H2O) and resistance (cm H2O/L/s) combinations of 20/20, 20/5, and 50/20 were used. Auto-PEEP, VT, and peak alveolar and airway opening pressures increased as TGI and Ti increased, regardless of lung mechanics settings (p<0.01). All increases were greater with VCV than PCV (p<0.05). Continuous flow TGI with both PCV and VT-uncorrected VCV may result in marked increases in Vt and system pressures, especially at long TI.
Lack of bleeding in patients with severe factor VII deficiency
Authors: J. Mark Barnett, Kurt C. Demel, Anthony E. Mega, James N. Butera, Joseph D. Sweeney
Journal: American Journal of Hematology (2005)

Factor VII deficiency, although rare, is now recognized as the most common autosomal recessive inherited factor deficiency. It is usually considered to be associated with bleeding only in the severely affected subject and heterozygotes (>10%) are not considered at risk. The general recommendation for surgery is to achieve a FVII level in excess of 15% (0.15 1U/mL). We present three cases of severe factor VII deficiency, each of whom appeared hemostatically competent based on clinical history. Subject 1 is a 33 year-old African-American female with a baseline FVII of <1%, who had a fractured tibia requiring open reduction with internal fixation without any FVII replacement and subsequently underwent successful laparoscopic knee surgery with a factor VII level measured at 6%. Subject 2 is a 58 year-old African-American female with a factor VII level of 9% who underwent an elective left total hip replacement without any factor replacement and had no excessive bleeding, but who sustained a pulmonary embolism postoperatively. Subject 3 is a 19-year-old African-American male with a baseline FVII of 1% with a history of active participation in football without noticeable injury and who underwent an emergent appendectomy without bleeding. These three cases represent individuals with the severe form of FVII deficiency who did not exhibit excessive bleeding when challenged with surgical procedures. The clinical history would appear the most valuable tool in predicting the likelihood of bleeding in these patients, and we suggest that the presumption that all patients with severe FVII deficiency should receive replacement therapy before surgical procedures may not be valid in all cases. Am. J. Hematol. 78:134–137, 2005. © 2005 Wiley-Liss, Inc.
Heterozygote Screening — A Social Challenge
Authors: Michael M. Kaback
Journal: New England Journal of Medicine (1973)

The technical capability to identify accurately healthy persons who carry deleterious recessive genes (heterozygotes) poses important new challenges for the medical, public-health and social science professions. Carrier detection provides the foundation for the potential prevention and control of many human genetic diseases. In the families in which individuals have been identified with recessive disorders, carrier detection may greatly improve the accuracy of genetic counseling for unaffected relatives. In a larger sense, carrier identification for genes that have a particular predilection for a defined subpopulation may enable the identification of individuals or couples at risk for such genetic disease in their . . .
Topical Application of Cream-emulsified CD86 siRNA Ameliorates Allergic Skin Disease by Targeting Cutaneous Dendritic Cells
Authors: Patcharee Ritprajak, Masaaki Hashiguchi, Miyuki Azuma
Journal: Molecular Therapy (2008)

Induction of the co-stimulatory molecule CD86 on dendritic cells (DCs) in the peripheral tissues is a critical event in triggering antigen-specific immune responses. In this study, we propose a new small interfering RNA (siRNA)-based therapy using cream-emulsified CD86 siRNA, targeting DCs for murine contact hypersensitivity (CH) and atopic dermatitis (AD)-like disease. Topical application of CD86 siRNA efficiently inhibited CH and markedly decreased the numbers of infiltrating CD86(+) or major histocompatibility complex (MHC) class II(+) cells in murine ear skin. The total number of cells, the percentage of hapten-carrying DCs, and their CD86 expression in the regional lymph nodes (RLNs) also significantly decreased. These results suggest that the silencing of CD86 in local DCs inhibits the recruitment and migration of DCs into the skin and RLNs, respectively, resulting in reduced antigen-specific local inflammation. The therapeutic efficacy of the CD86 siRNA was confirmed in AD-prone NC/Nga mice. Treatment produced marked amelioration in the clinical manifestations of AD and reduced the antigen-specific production of interleukin-4 (IL-4) and serum immunoglobulin E (IgE) and IgG1. Our results suggest that the targeting of cutaneous DCs by CD86 siRNA may be a promising strategy in the treatment of allergic skin disease.
Improvement in bronchial hyper-responsiveness in patients with moderate asthma after treatment with a hypnotic technique: a randomised controlled trial.
Authors: T C Ewer, D E Stewart
Journal: BMJ (1986)

We had previously shown that the in vitro antibody response to a single epitope (ese; extra sheep E Ag) present on some sheep E but absent from others could be monitored by assay of the plaque-forming cell response on both Lo3 and Hi SRBC. We had shown also that the response was seen only in certain strains of mice and that the gene(s) controlling the response mapped to the IgH V region of the IgH chain complex. An additional feature of the response is that it is only seen in vitro and is absent and, we hypothesize, is suppressed in vivo. The strain distribution of the response to the ese determinant suggested that the response may only use one V gene (or a small set of closely related V genes) that would be present in the responder strains and absent from the nonresponder strains. To test this hypothesis, we made hybridomas with specificity for the ese determinant and for the shared determinants. cDNA from these hybridomas were sequenced. All four anti-ese hybridomas were almost identical in V region sequence, but varied considerably in D and J segment usage, thus confirming the hypothesis that the ese response would be limited at the V segment. The four anti-ese hybridomas used two Vh J558 genes that differed only by one, or possibly two, nucleotide(s). Importantly, these genes are quite different from most other published J558 sequences. The sequence is very similar to an unexpressed sequence from a C57Bl/6 perinatal mouse and slightly less similar to two other Vhb sequences. It was quite similar to two sequences from autoantibodies, one an anti-DNA hybridoma antibody, BXW-14, isolated from an NZB x NZWF1 mouse, and the other, an NZB hybridoma, G8, with specificity for a mouse E Ag. We speculate that the Ig encoded by the V ese gene react with an autoantigen, that the B cells persist in the animal, but that the secretion of Ig is somehow suppressed.
Stability of Specialty Preferences Among Medical School Graduates
Authors: Robert G. Petersdorf
Journal: JAMA (1988)

<h3>To the Editor.—</h3> In a recent article on stability of specialty preferences, Babbott et al<sup>1</sup>included within their definition of primary care the subspecialties of internal medicine and pediatrics. With this unconventional definition, the authors report that 47.5% of the male graduates and 55.7% of the female graduates planned to enter primary care specialties. It seems unjustified to count the subspecialties under primary care medicine. With this revision, fewer than 40% of our graduates will end up as generalists, a figure well below that endorsed by the academic establishment 15 years ago. It is not a salubrious picture.
Wartime Arrangements for International Biological Standards
Authors: H. H. Dale
Journal: BMJ (1942)

The International Standards for l emedies of which the strength has to be measured by biological methods came into being between the two world wars, through action by the Health Organization of the League of Nations.The work was by no means limited, however, to the nations that had joined the League.Important shares in the enter- prise, which began in 1921 on Dr. Madsen's initiative, were taken at the outset by experts from the countries that had not yet been admitted, and during the whole period by those from the United States of America.Even when Germany and her associates later withdrew from the League the international standards remained in use among their men of science, though without official recognition, and German industry continued to make important contri- butions to the materials required for the preparation of new standards.There could be no doubt that these international standards were worth preserving for their value to research as well as to practical therapeutics, and it was clearly imperative that war should not endanger the existence of materials which embodied so much work of investigation, freely given to this common enterprise by leading experts of many nationalities.Steps were, in fact, very promptly taken by Dr. Hartley, Director of the Department of Biological Standards at the National Institute for Medical Research, to see that adequate quantities of the international standards held in that department were sent to the control centres of other countries, to meet any probable interruption of normal distribution; while the main stocks were so distributed as to minimize the risk of their destruction.
Personality in epilepsy.
Authors: Samuel Livingston
Journal: JAMA (1963)

Much has been written in the past about the existence of an "epileptic personality." Almost every type of behavioral and personality aberration has been assigned to the epileptic as a manifestation of his "epileptic personality." Even today, many laymen, and also some physicians, express the attitude that most epileptics have or will subsequently develop "psychopathic personalities." None of these attitudes, however, is based on scientifically valid information. Guerrant and co-workers present the first comprehensive, controlled study relative to the personality of the epileptic. Their study is based on three groups of patients: one with psychomotor epilepsy, one with grand mal epilepsy, and the third with chronic illnesses, such as diabetes mellitus, coronary artery disease, and bronchiectasis. It is well known that many epileptics present emotional problems. The findings of these workers corroborate this fact. However, they demonstrated that the two epileptic groups (psychomotor and grand mal) were only slightly more
Transplantation: The Problem of Limited Resources
Authors: John K. Iglehart
Journal: New England Journal of Medicine (1983)

A congressional inquiry, designed originally to evaluate current methods of securing human organs for transplantation, has helped alert federal policy makers to inadequacies in that system. But along the way, the inquiry also uncovered some other serious aspects of the profound dilemma that third parties will increasingly face in deciding whether to pay for costly new transplantation procedures and also involving the chaotic process by which emerging technologies are evaluated for their medical efficacy.The interest of the legislators who were party to the inquiry, undertaken by the House Science and Technology Subcommittee on Investigations and Oversight, was provoked by . . .
The contribution of genetic risk factors other than the HLA shared epitope alleles to the genetic variance of rheumatoid arthritis
Authors: Diane van der Woude, Jeanine J Houwing-Duistermaat, Ann Morgan, Jane Worthington, Tom W J Huizinga, Bart O Roep, René E M Toes, René R P de Vries
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> Genetic factors explain 66% of susceptibility to rheumatoid arthritis, but it is unclear how much of this genetic risk can be explained by the genetic risk factors known to date. In addition to the contribution of the HLA shared epitope (SE) alleles which the authors have quantified previously, the authors now investigated the contribution of the protective HLA-DRB1*13 alleles and of 12 replicated single nucleotide polymorphisms (SNPs), to the genetic variance of total, anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA. <h3>Methods</h3> A cohort of 148 twin pairs, of which at least one twin had RA, were tested for ACPA. The contribution of the HLA-DRB1 alleles and SNPs to the genetic variance was assessed by a logistic regression model with genotype-specific parameters and a random effect model representing the contribution of unobserved genetic factors. <h3>Results</h3> In the ACPA-positive subset, the HLA SE alleles contributed 19.2% to the genetic variance, while the contribution of the protective HLA-DRB1*13 alleles was very small: 0.13%. Both SE and DRB1*13 alleles hardly contributed to ACPA-negative RA (1.52%). The contributions of the separate SNPs to the different subsets of RA were small with an average of below 1%. <h3>Conclusion</h3> A modest amount of the genetic variance of ACPA-positive, but not ACPA-negative RA can be explained by the HLA SE alleles, while the contribution of the protective HLA-DRB1*13 alleles and non-HLA loci is very small. These results indicate that the largest part of the genetic contribution to RA remains unexplained.
How protective is the working time directive?: … but Australia may have a way forward
Authors: Cameron Burrows
Journal: BMJ (2004)

Cholesterol values seem to divergeEditor-The targets for cholesterol management seem to be ever decreasing, but I cannot get my head around the fact that in the new guidelines from the British Hypertension Society box 8 suggests we should consider treatment if the 10 year risk of cardiovascular disease is > 20% and the total cholesterol level is > 3.5 mmol/l but the target to be attained, which is printed beside box 8, is higher, 4 mmol/l. 1 Can someone explain this anomaly to a simple general practitioner who will have to explain it to patients?
Stored tissue may be important for the future care of families
Authors: N. Haites
Journal: BMJ (2001)

EDITOR—Obtaining informed consent for storing tissue is problematic. Which normal clinical practices need written consent and what material constitutes tissue? In how much detail should a practitioner obtain consent for a blood sample taken for a full blood count or for biochemical analysis, and what information can or should be given about the ultimate fate of samples such as tumours removed at surgery?

These are not trivial questions: their answers lie at the heart of good clinical practice. …
Late incomplete stent apposition following sirolimus-eluting stent: Serial quantitative intravascular ultrasound analysis from the SIRIUS trial
Authors: Junya Ako, Yoshihiro Morino, Yashuhiro Honda, Shinjo Sonoda, Mitsuyasu Terashima, Ali Hassan, Martin B. Leon, Jeffrey W. Moses, Steve Osterle, Charles L. Brown, Donald S. Baim, Paul G. Yock, Peter J. Fitzgerald
Journal: Journal of the American College of Cardiology (2003)
Improved Tissue Repair in Articular Cartilage Defects in Vivo by rAAV-Mediated Overexpression of Human Fibroblast Growth Factor 2
Authors: Magali Cucchiarini, Henning Madry, Chunyan Ma, Tanja Thurn, David Zurakowski, Michael D. Menger, Dieter Kohn, Stephen B. Trippel, Ernest F. Terwilliger
Journal: Molecular Therapy (2005)

Therapeutic gene transfer into articular cartilage is a potential means to stimulate reparative activities in tissue lesions. We previously demonstrated that direct application of recombinant adeno-associated virus (rAAV) vectors to articular chondrocytes in their native matrix in situ as well as sites of tissue damage allowed for efficient and sustained reporter gene expression. Here we test the hypothesis that rAAV-mediated overexpression of fibroblast growth factor 2 (FGF-2), one candidate for enhancing the repair of cartilage lesions, would lead to the production of a biologically active factor that would facilitate the healing of articular cartilage defects. In vitro, FGF-2 production from an rAAV-delivered transgene was sufficient to stimulate chondrocyte proliferation over a prolonged period of time. In vivo, application of the therapeutic vector significantly improved the overall repair, filling, architecture, and cell morphology of osteochondral defects in rabbit knee joints. Differences in matrix synthesis were also observed, although not to the point of statistical significance. This process may further benefit from cosupplementation with other factors. These results provide a basis for rAAV application to sites of articular cartilage damage to deliver agents that promote tissue repair.