tbuckley/cabot-search huggingface dataset:
Paucity of TEL‐AML 1 translocation, by multiplex RT‐PCR, in B‐lineage acute lymphoblastic leukemia (ALL) in Indian patients
Authors: S. Sazawal, K. Bhatia, M.I. Gutierrez, R. Saxena, L.S. Arya, M. Bhargava
Journal: American Journal of Hematology (2004)

A total of 69 patients of B lineage ALL, 35 children (32 males, 3 females) and 34 young adults (27 males, 7 females) were studied by multiplex RT-PCR to determine the relative frequency of t(9;22), t(12;21), t(1;19), and t(4;11,). Translocation (9;22) was seen in 1/35 (2.8%) and t(1;19) in 2/35 (5.7%) children. None of the children showed t(12;21) and t(4;11) translocations. In young adults, t(9;22) and t(1;19) were seen in 5/34 (14.7%) and 2/34 (5.8%) patients, respectively. None of the latter showed t(12;21) or t(4;11) translocations. Thus, there appears to be a significant under representation of the fusion transcripts for TEL-AML, a good prognostic marker, in this study, unlike in the West, where it is seen in 35% of children with ALL. This, together with the generally increased leukemic burden seen in Indian patients, may explain in part, the poor treatment outcome reported.
Cytochrome c Oxidase Assembly in Primates is Sensitive to Small Evolutionary Variations in Amino Acid Sequence
Authors: Antoni Barrientos, Stefan Müller, Runu Dey, Johannes Wienberg, Carlos T. Moraes
Journal: Molecular Biology and Evolution (2000)

Respiring mitochondria require many interactions between nuclear and mitochondrial genomes. Although mitochondrial DNA (mtDNA) from the gorilla and the chimpanzee are able to restore oxidative phosphorylation in a human cell, mtDNAs from more distant primate species are functionally incompatible with human nuclear genes. Using microcell-mediated chromosome and mitochondria transfer, we introduced and maintained a functional orangutan mtDNA in a human nuclear background. However, partial oxidative phosphorylation function was restored only in the presence of most orangutan chromosomes, suggesting that human oxidative phosphorylation-related nuclear-coded genes are not able to replace many orangutan ones. The respiratory capacity of these hybrids was decreased by 65%–80%, and cytochrome c oxidase (COX) activity was decreased by 85%–95%. The function of other respiratory complexes was not significantly altered. The translation of mtDNA-coded COX subunits was normal, but their steady-state levels were ∼10% of normal ones. Nuclear-coded COX subunits were loosely associated with mitochondrial membranes, a characteristic of COX assembly-defective mutants. Our results suggest that many human nuclear-coded genes not only cannot replace the orangutan counterparts, but also exert a specific interference at the level of COX assembly. This cellular model underscores the precision of COX assembly in mammals and sheds light on the nature of nuclear-mtDNA coevolutionary constraints.
Abstract 2941: Inhibition of proteasome deubiquitinating activity as a novel cancer therapy
Authors: Pádraig D'Arcy1, Slavica Brnjic1, Maria H. Olofsson, Marten Fryknas, Rolf Larsson, Stig T. Linder
Journal: Cancer Research (2012)

Abstract Tumor cells display enhanced sensitivity to disruptions in the ubiquitin-proteasome system making this an attractive target for the development of anti-cancer therapies. Ubiquitin-tagged substrates are degraded by the 26S proteasome; a multisubunit complex comprising a proteolytic 20S core particle (20S CP) capped by 19S regulatory particles (19S RP). The 20S CP has evolved as an important target for anti-cancer drug development, resulting in the approval of bortezomib (Velcade®) for the treatment of multiple myeloma. We have identified the small molecule b-AP15 as a novel class of proteasome inhibitor that functions by abrogating the deubiquitinating (DUB) activity of the 19S RP (D'Arcy, Brnjic et al., Nature Medicine Epub Nov 6 2011). b-AP15 inhibits the activity of two 19S RP-associated DUBs, UCHL5 and USP14. Consistent with DUB inhibition, treatment with b-AP15 caused the accumulation of polyubiquitinated proteins with higher molecular weight compared to bortezomib treatment and induced a stronger proteotoxic response. Short exposures were sufficient for induction of apoptosis by the compound. Importantly, apoptosis induction by b-AP15 differed from that of bortezomib by being insensitive to disruptions of the p53 tumor suppressor and insensitive to overexpression of the intrinsic apoptotic suppressor Bcl-2. b-AP15 shows strongest activity on colon and glioma tumor cell lines and is less active on non-transformed cells. Treatment with b-AP15 inhibited tumor progression in human and mouse tumor in vivo models of breast, lung, colon, head &amp; neck carcinoma and inhibited organ infiltration in an acute myeloid leukemia (AML) model. Our results suggest that inhibiting the DUB activity of the 19S RP may be a novel target for the treatment of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2941. doi:1538-7445.AM2012-2941
THE VAGINAL DOUCHE IN ITS RELATIONS TO BLENNORRHEA IN THE FEMALE.
Authors: E. R. PALMER
Journal: JAMA (1895)

To be concise, to avoid irrelevancy, to be up to date, to be orthodox, is the aim of this paper. What is blennorrhea or gonorrhea, as you may please to call it? The following quotations from Finger<sup>1</sup>embody my answer of this question and will be the basis of my argument: "So many positive inoculations have been made that doubt of the pathogenic character of the gonococci is hardly possible at the present time; in fact its etiologic significance is not recognized universally except by a small group of French writers." Further on, after viewing the full history of laboratory research in this matter he says: "If we make a résumé, the following facts may be regarded as well established: "1. The gonococcus is found in all cases of suppuration of the mucous membranes, especially of the genitalia and conjunctiva which are described clinically as gonorrheal. "2. It is
Deviations From Guideline-Based Therapy for Febrile Neutropenia in Cancer Patients and Their Effect on Outcomes
Authors: Jason D. Wright, Alfred I. Neugut, Cande V. Ananth, Sharyn N. Lewin, Elizabeth T. Wilde, Yu-Shiang Lu, Thomas J. Herzog, Dawn L. Hershman
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3>Although febrile neutropenia (FN) is a major source of morbidity and mortality for patients with solid tumors, little is known about the use of guideline-based care.<h3>Objectives</h3>To examine compliance with guideline-based recommendations for FN treatment, explore the factors that influence adherence to consensus guidelines, and analyze how the use of guideline-based care affects the outcomes.<h3>Design</h3>The Perspective database was used to examine the treatment of cancer patients with FN from January 1, 2000, through March 31, 2010. To capture initial decision making, we examined treatment within 48 hours of hospital admission. We determined use of guideline-based antibiotics and nonguideline-based treatments, vancomycin, and granulocyte colony-stimulating factors (GCSF). Hierarchical models were developed to examine the factors associated with treatment. Patients were stratified into low- and high-risk groups, and the effect of the initial treatment on outcome (nonroutine hospital discharge and death) was examined.<h3>Setting and Participants</h3>Twenty-five thousand two hundred thirty-one patients with solid tumors hospitalized for neutropenia.<h3>Main Outcome Measure</h3>Use of guideline-based antibiotics, vancomycin, and GCSF and their affect on outcome.<h3>Results</h3>Among 25 231 patients admitted with FN, guideline-based antibiotics were administered to 79%, vancomycin to 37%, and GCSF to 63%. Patients treated at high FN-volume hospitals (odds ratio [OR], 1.56; 95% CI, 1.34-1.81) by high FN-volume physicians (OR, 1.19; 95% CI, 1.03-1.38) and patients managed by hospitalists (OR, 1.49; 95% CI, 1.18-1.88) were more likely to receive guideline-based antibiotics (P &lt; .05). Vancomycin use increased from 17% in 2000 to 55% in 2010, while GCSF use only decreased from 73% to 55%. Among low-risk patients with FN, prompt initiation of guideline-based antibiotics decreased discharge to a nursing facility (OR, 0.77; 95% CI, 0.65-0.92) and death (OR, 0.63; 95% CI, 0.42-0.95).<h3>Conclusions and Relevance</h3>While use of guideline-based antibiotics is high, use of the nonguideline-based treatments, vancomycin, and GCSF is also high. Physician and hospital factors are the strongest predictors of both guideline- and nonguideline-based treatment.
Iatrogenic spreading of liver derived cells by liver resection and needle biopsy in patients with primary liver cancer
Authors: M. Louha, J. Nicolet, M. Sabile, H. Zylberberg, C. Vons, G. Vona, F. Capron, K. Poussin, S. Pol, S.B. Nalpas, D. Franco, C. Bréchot, P. Paterlini
Journal: Journal of Hepatology (1998)
The Migratory Needle Story.
Authors: L. D. Wilson.
Journal: JAMA (1906)

Wheeling, W. Va., Nov. 17, 1906. <h3>To the Editor:</h3> —The editorial with the above caption, inThe Journal, November 17, prompts the relation of the following circumstance: About 20 years ago a woman, aged 60, consulted me in regard to an obscure discomfort, amounting at times to pain, which she experienced in one of her legs. As there existed a moderate varicose condition of the veins, and as there did not appear to be any other probable cause for the trouble, I suggested that she try an elastic bandage. Instead of relief, this caused a considerable increase in the degree of discomfort. Having worn the bandage for a few days only, she took it off one day to take a bath. While in the bathtub, on passing her hand over the outer aspect of the upper third of the thigh, where she felt a little soreness, she was startled and
Three Successive Attacks of Subacute Bacterial Endocarditis Due to Different Organisms
Authors: M. Hallowell
Journal: BMJ (1958)

OBJECTIVE: To describe our experience with low dose weekly methotrexate (MTX) in the management of immune mediated cochleovestibular disorder (IMCVD). METHODS: Between 1991 and 1999, we treated 53 patients with IMCVD with MTX. Patients were selected on the basis of progressive vestibular symptoms that had responded to corticosteroids and in most cases, relapsed. MTX was initiated at a dose of 7.5 mg weekly and increased to doses up to 25 mg weekly as needed. Response was assessed by audiologic studies and history of change in tinnitus and vertigo. MTX was discontinued after 4-6 mo in patients showing no improvement, and after 12-18 mo in patients with improved and stable symptoms. RESULTS: Three patients were still in early therapy and had not improved. Of the 50 remaining patients, significant improvement was seen in vertigo in 27/39 (69%) patients, hearing loss in 25/47 (53%), and tinnitus in 11/42 (26%). Overall improvement in symptoms was seen in 35/50 (70%) patients. Four patients stopped MTX due to toxicity, and 11 due to lack of response. In 28 patients, MTX was stopped after 12-18 mo when symptoms had stabilized, and restarted in 5 of these after relapse. Seven patients remain on therapy with improved and stable symptoms after 17.3 mo. CONCLUSION: In this open label experience, a majority of patients with IMCVD improved with weekly low dose MTX therapy with minimal toxicity.
Paradoxical Pulse in Constrictive Pericarditis-Reply
Authors: E. William Hancock
Journal: JAMA (1975)

In Reply.—  Paradoxical pulse undoubtedly does occur in some instances of inactive chronic constrictive pericarditis. Dr Sasse makes an interesting and useful point that analysis of the respiratory changes in timing of A2and P2may show correlations with various degrees of paradoxical pulse. The relationship of inspiratory variations in venous return to paradoxical pulse in various types of pericardial disease is not completely elucidated and should be studied further, perhaps with Doppler flow-pattern studies and with echocardiographic studies of cardiac dimensions.
Dasatinib as first-line treatment for adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia
Authors: Robin Foà, Antonella Vitale, Marco Vignetti, Giovanna Meloni, Anna Guarini, Maria Stefania De Propris, Loredana Elia, Francesca Paoloni, Paola Fazi, Giuseppe Cimino, Francesco Nobile, Felicetto Ferrara, Carlo Castagnola, Simona Sica, Pietro Leoni, Eliana Zuffa, Claudio Fozza, Mario Luppi, Anna Candoni, Ilaria Iacobucci, Simona Soverini, Franco Mandelli, Giovanni Martinelli, Michele Baccarani
Journal: Blood (2011)
THE THERAPEUTIC VALUE OF NEPHROPEXY
Authors: W. Billington
Journal: BMJ (1928)

society entitled " The indicationis for nephropexy,'" a paper whiclh n-as subsequenitly publislhed in the British Mledical Jouriial.At that time the subject was a very live one in Birmiiinghanm; the meetinig was largely attended, and very strong views were expressed both for and against the
Blunt Hepatic and Splenic Trauma: Where Have All the Surgeons Gone?
Authors: Christopher C. Baker
Journal: Hepatology (1990)

To further define the computed tomographic (CT) criteria on which to guide the nonsurgical treatment of adult patients with blunt hepatic injury, the authors retrospectively reviewed abdominal CT scans obtained before surgery during a 35–month period. Blunt hepatic injury was diagnosed in 187 patients, and review revealed 37 patients in whom the liver was the site of sole or principal intraabdominal injury detected with the help of CT before surgery. A CT–based hepatic injury classification system partly derived from similar systems established with surgical assessment was devised to grade the severity of hepatic injury. CT–based injury scores ranging from grade 1 to 5 were compared with the clinical outcome in patients treated surgically and nonsurgically. Thirty–one patients (83.7%) were successfully treated without surgery, and four patients (10.8%) had findings at celiotomy that did not require further surgery. No patient who was initially treated without surgery required delayed celiotomy due to hepatic injury. The results indicate that even major hepatic injury up to and including grade 4 severity assessed with preoperative CT can usually be managed without surgery in hemodynamically stable patients. Nonsurgical management of blunt splenic injury in children is a well–established method to salvage splenic function; however, nonsurgical management of adult blunt splenic trauma remains controversial. To assess the value of preoperative abdominal CT in predicting the outcome of blunt splenic injury in adults, a CT based injury–severity score consisting of four grades was devised and applied in 39 adult patients with blunt splenic injury as the sole or predominant intraperitoneal injury detected with preoperative CT. While patients with high grades of splenic injury generally required early surgery, eight (35%) of 23 patients with initial grade 3 or 4 injury were treated successfully without surgery, and four (29%) of 15 patients with grade 1 or 2 injury initially treated nonsurgically required delayed celiotomy (n = 3) or emergency rehospitalization. Results show that while CT remains an accurate method of identifying and quantifying initial splenic injury, as well as documenting progression or healing of critical injury, CT cannot reliably help predict the outcome of blunt splenic injury in adults. Treatment choices should therefore be based on the hemodynamic status of the patient and results of serial laboratory and bedside assessments.
Government looks at ways to reduce the cost of NHS negligence claims
Authors: C. Dyer
Journal: BMJ (2011)

<h3>ABSTRACT</h3> A classic example of antibiotic inactivating function in bacteria is the <i>Mycobacterium smegmatis</i> (<i>Msm</i>) encoded rifampicin-inactivating mono-ADP-ribosyl transferase (<i>arr</i>). Since its probable biological role has been proposed to be in DNA damage response, which is inflicted by reactive oxygen species (ROS), in the present study, we examined whether <i>Msm</i> Arr influences ROS levels. For this purpose, the levels of the ROS, hydroxyl radical and superoxide, were determined in the mid-log phase (MLP) cells of <i>Msm arr</i> knockout (<i>arr</i>-KO) strain, in comparison to those in the equivalently grown <i>Msm arr</i><sup>+</sup> wild-type (WT) strain. The MLP <i>arr</i>-KO cells generated significantly elevated levels of superoxide and hydroxyl radical, unlike the equivalently grown WT MLP cells. Complementation of <i>arr</i>-KO with <i>arr</i>, but not with empty vector, restored the ROS levels comparable to those in the WT strain. Elevated ROS levels in the <i>arr</i>-KO strain enabled selection of rifampicin-resistant mutants at 10<sup>-7</sup> cfu/ml from the rifampicin-unexposed MLP cells of <i>arr</i>-KO, which is one-log<sub>10</sub> higher than that for WT cells (10<sup>-8</sup>). Upon prolonged exposure to rifampicin, the susceptibility, persister formation, generation of elevated levels of hydroxyl radical by the persisters, rifampicin-resister generation frequency of the persisters and regrowth of the rifampicin-resistant mutants from the respective persisters were all comparable between the <i>arr</i>-KO and WT strains. These observations revealed that Arr influences ROS levels in the actively growing <i>M. smegmatis</i> cells but not in the rifampicin-exposed cells. We proposed the probable pathway through which Arr might be influencing ROS levels in the actively growing <i>M. smegmatis</i> cells. <h3>IMPORTANCE</h3> Diverse genera of bacteria consisting of pathogens, opportunistic pathogens and non-pathogens, possess Arr-type activities that confer equally efficient rifampicin resistance, thereby posing serious health hazard. Acquisition of this function by other bacteria through horizontal gene transfer enhances the hazard posed by the bacteria possessing it. <i>M. smegmatis</i> is an opportunistic human pathogen that causes infections of skin and soft tissues. Moreover, <i>M. smegmatis</i> is a genetically tractable model organism for <i>M. tuberculosis</i> with the potential to function even as tuberculosis vaccine. In view of these significant aspects of Arr and <i>M. smegmatis</i>, the study to find out the natural physiological role of Arr in <i>M. smegmatis</i>, gains importance for designing strategies to prevent antibiotic inactivation and to target the cellular function to contain the bacterium. Above all, the three-dimensional structure of <i>M. smegmatis</i> Arr reveals significant structural homology with eukaryotic ADP-ribosyltransferases and bacterial toxins, thereby giving the study broad significance.
Magnetic resonance imaging and different levels of Iron overload in chronic liver disease
Authors: Emilio Rocchi, Marco Cassanelli, Athos Borghi, Franco Paolillo, Marcello Pradelli, Giovanna Casalgrandi, Aldo Burani, Ennio Gallo
Journal: Hepatology (1993)

The need for accurate and noninvasive evaluation of liver iron stores prompted us to evaluate the reliability of high-field magnetic resonance imaging equipment in liver patients with low or moderate siderosis, given the poor results obtained using systems operating at low field strength in such cases. Twenty patients with sporadic porphyria cutanea tarda and 28 with comparable chronic liver diseases (chronic hepatitis or cirrhosis) and moderate siderosis were compared with 10 patients with idiopathic or secondary hemochromatosis and 10 healthy controls. Plasma iron profile, ferritin concentration and liver iron concentration, determined with atomic absorption spectroscopy, were matched with the magnetic resonance parameters-namely, transverse relaxation time and the signal intensity for a given proton amount, obtained with equipment operating at a field strength of 1.5 T. Hemochromatosis patients with mean liver iron concentrations of 550 mumol/gm dry wt (vs. 10 mumol of controls) exhibited an impressive reduction in the signal intensity with respect to the other three groups, and this reduction prevented any further comparison with the same porphyria cutanea tarda and chronic liver disease groups, whose liver iron level was twice that of the controls. The signal intensity remained almost unchanged in the latter groups, whereas the transverse relaxation time was significantly reduced. Moreover, correlation with liver iron was significantly inverse in the case of the transverse relaxation time (n = 17, r = 0.62, p = 0.008) and direct in the case of the transverse relaxation rate. The transverse relaxation time values returned to normal in five patients who had completed an iron-depletion program.(ABSTRACT TRUNCATED AT 250 WORDS)
Characteristics of sinoatrial conduction in patients with coronary artery disease.
Authors: J Jordan, I Yamaguchi, W J Mandel
Journal: Circulation (1977)

Electrophysiologic studies were performed in 32 patients with angiographically documented coronary artery disease (CAD). Group I was composed of ten patients (31%) with severe stenosis (greater than or equal to 75%) proximal to the origin of the sinus node artery (SNA); group II was composed of five patients (16%) with moderate (50--75%) proximal stenosis; and group III was composed of 17 patients (53%) with insignificant (0--50%) proximal stenosis. The mean sinoatrial conduction time (SACT) for group I was 119 +/- 18 msec; group II was 84+/- 16 msec; and group III was 72 +/- 5 msec. The SACT was significantly longer in group I than in group III (P less than 0.005). In conclusion 1) in patients with CAD, SACT greater than 72 +/- 5 msec is abnormal; 2) the results suggest a pathogenetic role of CAD in the development of sinus node dysfunction; 3) the SACT is a more sensitive indicator of subtle sinus node dysfunction in CAD patients than is heart rate, sinus node response to artrial extrastimuli, or sinus node recovery time; and 4) the ability to diagnose sinus node dysfunction in its early stages and recognition that coronary artery disease is an etiologic factor may allow for the elucidation of the natural history of the sick sinus syndrome.
Thyroid function tests and hypothyroidism: Restoring serum TSH to reference range should be goal of replacement
Authors: M. P Vanderpump
Journal: BMJ (2003)

EDITOR—The article from Meier et al concludes that judicious initiation of thyroxine treatment in overt hypothyroidism should be guided by clinical and metabolic presentation and thyroid hormone concentrations and not by serum thyroid stimulating hormone concentrations.1 This conclusion seems to contradict overwhelming evidence that serum thyroid stimulating hormone represents the most sensitive …
Quality of care and mortality in pediatric intensive care units
Authors: B. D. Kan
Journal: JAMA (1995)

To the Editor.  —I agree with Dr Pollack and his colleagues' 1 major finding that variations in mortality rates in pediatric intensive care units (ICUs) may be partially explained by variables such as presence of a pediatric intensivist and teaching hospital status. However, I do not agree with the authors' post hoc analysis, which suggests that care by pediatric residents is associated with increased mortality. The authors fail to point out alternative explanations for their analysis, and their data are not entirely consistent with their conclusions.  The authors found that teaching hospital status was significantly associated with increased mortality rates, even after adjusting for case mix severity. It is not surprising that the presence of pediatric residents was also a predictor of mortality since they are highly correlated variables (teaching hospitals are the primary sites for training pediatric residents). The authors' statistical model found that the presence of pediatric residents