tbuckley/cabot-search huggingface dataset:
NEPHRECTOMY and its RELATION to PREGNANCY
Authors: G. E. Twynam
Journal: BMJ (1898)

NEPHRECOCOMY AND PREGNANCY.Tk'Bt 423 do not quickly become alarming, and cases of this kind may last a fortnight or more before death occurs, as it invariably does unless relief is given by operation.The following is the history of such a case: CASE III.-On July 16th, I897, a boy aged iT, apparently in good health, Cell from a wall.During the whole of the following week he complained frequently of pains in the belly.On July 22nd, as the pain was worse and he began to vomit and to pass slimy, offensive motions, a doctor was summoned.Under srmall doses of morphine he at first greatly improved, but on July 27th, eleven days after the fall from which ¶he dated the first symptoms, he seemed worse, and I saw him in consultation, The boy was slightly flushed.but had a perfectly tranquil expression.Just before my arrival he had got out of bed and passed a normal motion.'The mouth was dry; the abdomen showed slight general distension and marked rigidity and tenderness, the latter chiefly on the left side, to which most of the pain had also been referred.There was no localised swelling in the right iliac region, ard no tenderness of McBurney's point.Per rectum there was a tense.elastic swelling in the recto-vesical ouch.The diagnosis hesitated between general peritonitis arising from the appendix, and intussusception only partially strangulated.On opening the abdomen, a large quantity of stinking pus was found in the ,pelvis and in both flanks.The appendix was perforated, and a small concretion which had escaped from it was found in the pelvic pouch.The appendix and a large piece of infiltrated omentum were removed.?he boy made an excellent recovery, and is now quite well.
Loss of Epigenetic Modification Driven by the Foxp3 Transcription Factor Leads to Regulatory T Cell Insufficiency
Authors: Matthew L. Bettini, Fan Pan, Maria Bettini, David Finkelstein, Jerold E. Rehg, Stefan Floess, Bryan D. Bell, Steven F. Ziegler, Jochen Huehn, Drew M. Pardoll, Dario A.A. Vignali
Journal: Immunity (2012)
Low rates of naturally occurring resistant variants to the NS5A inhibitor daclatasvir in HCV-1 null responders
Authors: Enrico Galmozzi, Alessio Aghemo, Massimo Colombo
Journal: Hepatology (2012)

We read with interest the article by Sun et al.1 evaluating the influence of naturally occurring polymorphisms on the potency of the hepatitis C virus (HCV) nonstructural protein 5A (NS5A) replication complex inhibitor BMS-790052 (daclatasvir). To date, all substitutions resistant to Daclatasvir have been mapped to the first 100 amino acids of NS5A.2 The authors replaced the NS5A coding region of the HCV-1a and HCV-1b laboratory strains, H77c and Con1, with the corresponding regions of baseline (BL) specimens of 10 HCV-1a and HCV-1b-infected subjects. By this method the authors found that the BL-linked variant, Q30R-E62D, was responsible for the resistant phenotype of one HCV-1a subject, whereas the linked variant Q54H-Y93H displayed minimal resistance in one HCV-1b subject. Therefore, the authors suggest that BL polymorphisms in NS5A may significantly affect the emergence of resistance, providing additional challenges for the evaluation of variants associated with clinical failures. To assess the naturally occurring rate of these resistant variants, we analyzed a cohort of HCV-1 null responders to pegylated-interferon (PegIFN) plus ribavirin (RBV) therapy. These patients are optimal candidates for a daclatasvir regimen as shown by phase II studies.3 By direct sequencing we analyzed the N-terminal region of the NS5A protein in 8 HCV-1a and 28 HCV-1b subjects. Viral RNA was isolated from the plasma and the NS5A gene was amplified by reverse transcriptase (RT) nested-polymerase chain reaction (PCR) using genotype-specific primers and Platinum Taq high-fidelity DNA polymerase (Invitrogen, Carlsbad, CA). Then, bidirectional DNA sequencing was performed using the BigDye Terminator v. 3.1 Cycle Sequencing Kit and ABI PRISM 310 Genetic Analyzer (Applied Biosystems, Foster City, CA). We found multiple substitutions in the first 129 amino acids of NS5A with no known resistance to daclatasvir (Table 1). No HCV-1a subject had the Q30R-E62D linked variant identified by Sun et al., while we found the Q54H-Y93H linked variant in one HCV-1b subject. Finally, all NS5A sequences from HCV-1b patients harbored changes at codon 28 and 30, which are of unknown significance.4 In conclusion, due to the low rates of naturally occurring resistant variants in the NS5A region found in HCV-1 null responders to PegIFN plus RBV, we do not support routine direct sequencing of HCV before starting daclatasvir. Enrico Galmozzi Ph.D.*, Alessio Aghemo M.D.*, Massimo Colombo M.D.*, * First Division of Gastroenterology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
Informing Physicians About Promising New Treatments for Severe Disease
Authors: Jack R. Harnes
Journal: JAMA (1990)

To the Editor.—  In their Special Communication, Drs Steinbrook and Lo 1 state: At minimum, we suggest that unconventional communications contain as much detail as a structured abstract in a medical journal.  I note that Dr Steinbrook is associated with the Los Angeles Times and I am aware that other major newspapers and television networks have physician or science reporters.  I suggest that, at minimum, the media have a responsibility to the public, including physicians, to critique medical news releases. When studies have inadequate numbers of subjects, have no control groups, or follow-up is inadequate, to cite but a few examples that should be apparent to any physicianreporter, the information provided in the news release should be commented on to alert the public of any possible deficiencies in the reports. When appropriate, the criticisms of other physician experts should be quoted in the articles.  Some years ago I discussed this
Enhancement by Recombinant Human Interferon Alfa of the Reversal of Multidrug Resistance by MRK-16 Monoclonal Antibody
Authors: W. E. Fogler, J. W. Pearson, K. Volker, K. Ariyoshi, H. Watabe, C. W. Riggs, R. H. Wiltrout, D. L. Longo
Journal: JNCI Journal of the National Cancer Institute (1995)

The anti-P-glycoprotein monoclonal antibody MRK-16 mediates the reversal of multidrug resistance. Recombinant human interferon alfa (rHuIFN alpha) enhances the cytotoxic activity of diverse chemotherapeutics and may modulate multidrug resistance.Our purpose was to determine the outcome of combination treatment with MRK-16, rHuIFN alpha-2a, and cytotoxic agents on tumor cells that express P-glycoprotein (Pgp).Three Pgp-expressing, multidrug-resistant human tumor cell lines were used: the MDR1 retrovirus-infected HT-29 colon adenocarcinoma (HT-29mdr1), the doxorubicin (Adriamycin)-resistant MCF-7 (AdrR MCF-7) breast carcinoma, and the de novo Pgp-acquired, HCT-15 colon carcinoma. The parental cell lines HT-29par and MCF-7 were used as controls. The in vitro effects of MRK-16 and rHuIFN alpha-2a were studied on: (a) chemosensitivity of parental and multidrug-resistant cell lines to vincristine, doxorubicin, or paclitaxel (Taxol); (b) intracellular drug concentrations; and (c) Pgp expression. The efficacy of vincristine alone or in combination with MRK-16 and/or rHuIFN alpha-2a was assessed against HT-29mdr1 cells in female, athymic NCr-nu/nu mice.For vincristine, the IC50 (i.e., the concentration that causes 50% inhibition of cell growth) was 7.0 ng/mL in HT-29mdr1 cells. Pretreatment of HT-29mdr1 cells with MRK-16 partially restored vincristine sensitivity (IC50 = 4.8 ng/mL), which was enhanced by noncytotoxic concentrations of rHuIFN alpha-2a (IC50 = 2.9 ng/mL) via a mechanism independent of Pgp modulation or [3H]vincristine efflux. rHuIFN alpha-2a potentiated MRK-16 reversal of multidrug resistance with both doxorubicin and paclitaxel on HT-29mdr1 cells and with vincristine on AdrR MCF-7 and HCT-15 tumor cells. Treatment of mice with 1 mg/kg vincristine weekly for 3 weeks, beginning 10 days after tumor injection, significantly increased the median survival times of the HT-29par tumor-bearing mice (60 days versus 35 days; P < .0001) but was only marginally therapeutic for HT-29mdr1 tumor-bearing mice (52 days versus 46 days). Pretreatment with MRK-16 (500 micrograms) and rHuIFN alpha-2a (5 x 10(4) U), alone or in combination, 24 hours before vincristine therapy did not affect the survival of HT-29par tumor-bearing mice. In contrast, the survival of mice bearing HT-29mdr1 tumors was significantly increased following treatment with MRK-16 before vincristine (80 days; P < .0001). Administration of a nontherapeutic dose of rHuIFN alpha-2a (5 x 10(4) U) with MRK-16 before vincristine treatment further increased the median survival times of HT-29mdr1 tumor-bearing mice (116 days; P < .0001).MRK-16 used in combination with rHuIFN alpha-2a was significantly more effective than MRK-16 in overcoming multidrug resistance.
Effects of maximal exercise stress on left ventricular function in patients with coronary artery disease using first pass radionuclide angiocardiography: a rapid, noninvasive technique for determining ejection fraction and segmental wall motion.
Authors: J A Jengo, V Oren, R Conant, M Brizendine, T Nelson, J M Uszler, I Mena
Journal: Circulation (1979)

Angiographically determined changes in segmental wall motion (SWM) and ejection fraction (EF) are sensitive indices of left ventricular (LV) function. To compare the effects of exercise on LV function, first pass radionuclide angiocardiography was used before and during maximal upright bicycle stress in patients with nonsignificantly stenosed coronary arteries, and in those with greater than 75% stenosis. Gamma camera acquisitions were made in the 30 degree RAO projection using a 20 mCi I.V. bolus of 99mTc-pertechnetate. In the control group (seven normals, one nonsignificant (CAD) the EF significantly increased between rest and exercise (0.65 +/- 0.03 to 0.81 +/- 0.03 (mean +/- SEM), p less than 0.005). In this group SWM measured over the two anterior and two inferoposterior segments uniformly increased. In the 11 patients with a history of angina and significant coronary artery obstruction, the EF did not change in three and significantly decreased in the remaining eight (0.57 +/- 0.04 to 0.45 +/- 0.03, p less than 0.005). In all 11 patients SWM either decreased or did not increase in the areas supplied by the significantly stenosed coronary arteries. Upright maximal stress angiocardiography appears to be well-suited for diagnosing ischemic heart disease and localizing the area of ischemic dysfunction.
SIMPLE OPERATION FOR RELIEF OF MILD TYPES OF ENTROPION AND ECTROPION OF LOWER LID
Authors: J. E. JENNINGS
Journal: JAMA (1924)

Among the cases of functional and organic entropion and ectropion seen by the ophthalmic surgeon, there are quite a few of such a mild type that they do not seem to justify a radical operation. Notwithstanding the irritation and annoyance they cause, these patients are often allowed to drift along with negative rather than positive treatment. For example, there is the type of entropion frequently seen in elderly people with flabby lids who develop a spasmodic contraction of the lower lid after the eye has been bandaged for a few days. The treatment that naturally suggests itself to the surgeon is to draw out the lid and fix it in position by means of flexible collodion or a strip of adhesive plaster. When these methods fail to give permanent relief, as they often do, then there are a variety of more radical operations to choose from; among these are Snellen's
Doctors support embryo selection to help ill siblings
Authors: L. Beecham
Journal: BMJ (2003)

We investigated the potential of dietary saturated fatty acids to reverse alcoholic liver injury despite continued administration of alcohol. Five groups (six rats/group) of male Wistar rats were studied. Rats in groups 1 and 2 were fed a fish oil-ethanol diet for 8 and 6 weeks, respectively. Rats in groups 3 and 4 were fed fish oil and ethanol for 6 weeks before being switched to isocaloric diets containing ethanol with palm oil (group 3) or medium-chain triglycerides (MCTs, group 4) for 2 weeks. Rats in group 5 were fed fish oil and dextrose for 8 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, nuclear factor-κB (NF-κB) activation, and mRNAs for cyclooxygenase-2 (Cox-2) and tumor necrosis factor-α (TNF-α). Endotoxin in plasma was determined. The most severe inflammation and fibrosis were detected in groups 1 and 2, as were the highest levels of endotoxin, lipid peroxidation, activation of NF-κB, and mRNAs for Cox-2 and TNF-α. After the rats were switched to palm oil or MCT, there was marked histological improvement with decreased levels of endotoxin and lipid peroxidation, absence of NF-κB activation, and reduced expression of TNF-α and Cox-2. A diet enriched in saturated fatty acids effectively reverses alcohol-induced necrosis, inflammation, and fibrosis despite continued alcohol consumption. The therapeutic effects of saturated fatty acids may be explained, at least in part, by reduced endotoxemia and lipid peroxidation, which in turn result in decreased activation of NF-κB and reduced levels of TNF-α and Cox-2.
THE ANTE-NATAL CLINIC
Authors: G. B. Smith
Journal: BMJ (1925)

ACH 7, '94] THE ANTE-NATAL CLINIC.tMEMCAL rJO in which respect this disease resembles poliomyelitis, and incidentally tuberculous meningitis-a disease wlhich often causes a good deal of difficulty in diagnosis.The protein content of the cerebro-spinal fluid rarely slhows any marked increase, whilst the reverse is the case in meniingitis, but 0.03 per cent. is sometimes met with.The chlorides are not altered-another point which in a doubtful case may prove of use in making a diagnosis of encephalitis as against meningitis.In the latter the clhlorides constantly show a small reduction.Any figure belo-w 0.68 per cent.would suggest meningitis very strongly.So, too, with the glucose content.In encephalitis tills is unaltered, or even slightly increased, whilst in cases of meningitis, and more particularly tuberculous meniingitis, the quantity is substantially diminished or absent.Changes in the blood are not striking-a small leucocytosis with a total count of 10,000 to 12,000 may be expected. DIFFERENTIAL DIAGNOSIS.Encephalitis may be extremely easy or impossible to diagnose.Ofteni it is much easier to recogniize fiom its sequels than during the initial stages.Whilst it is true that in many cases the disease has escaped recognitioni, it is no doubt also true that in the interest aroused by the advent of a new disorder-at any rate new withini our experience-many cases have been labelled encephalitis lethargica which were nothing of the kind.Of acute infec- tions, those most likely to cause trouble in diagnosis are influenza and tuberculous meningitis.The formier suggests encephalitis in those cases in which headache, prostration, drowsiness, anid fever are the prominent symptoms, wlhilst the latter may exactly reproduce the clinical picture of enicephalitis.The absence of such signs as retraction-of the abdomen, rigidity of the neck, Kernig's sign, and tache ere'brale
Extrasynaptic glutamate release through cystine/glutamate antiporter contributes to ischemic damage
Authors: Federico N. Soria, Alberto Pérez-Samartín, Abraham Martin, Kiran Babu Gona, Jordi Llop, Boguslaw Szczupak, Juan Carlos Chara, Carlos Matute, María Domercq
Journal: Journal of Clinical Investigation (2014)

During brain ischemia, an excessive release of glutamate triggers neuronal death through the overactivation of NMDA receptors (NMDARs); however, the underlying pathways that alter glutamate homeostasis and whether synaptic or extrasynaptic sites are responsible for excess glutamate remain controversial. Here, we monitored ischemia-gated currents in pyramidal cortical neurons in brain slices from rodents in response to oxygen and glucose deprivation (OGD) as a real-time glutamate sensor to identify the source of glutamate release and determined the extent of neuronal damage. Blockade of excitatory amino acid transporters or vesicular glutamate release did not inhibit ischemia-gated currents or neuronal damage after OGD. In contrast, pharmacological inhibition of the cystine/glutamate antiporter dramatically attenuated ischemia-gated currents and cell death after OGD. Compared with control animals, mice lacking a functional cystine/glutamate antiporter exhibited reduced anoxic depolarization and neuronal death in response to OGD. Furthermore, glutamate released by the cystine/glutamate antiporter activated extrasynaptic, but not synaptic, NMDARs, and blockade of extrasynaptic NMDARs reduced ischemia-gated currents and cell damage after OGD. Finally, PET imaging showed increased cystine/glutamate antiporter function in ischemic rats. Altogether, these data suggest that cystine/glutamate antiporter function is increased in ischemia, contributing to elevated extracellular glutamate concentration, overactivation of extrasynaptic NMDARs, and ischemic neuronal death.
Gene expression–based classification and regulatory networks of pediatric acute lymphoblastic leukemia
Authors: Zhigang Li, Wei Zhang, Minyuan Wu, Shanshan Zhu, Chao Gao, Lin Sun, Ruidong Zhang, Nan Qiao, Huiling Xue, Yamei Hu, Shilai Bao, Huyong Zheng, Jing-Dong J. Han
Journal: Blood (2009)
Inhibition of Platelet Aggregation by AZD6140, A Reversible Oral P2Y12Receptor Antagonist, Compared With Clopidogrel in Patients With Acute Coronary Syndromes
Authors: Robert F. Storey, Steen Husted, Robert A. Harrington, Stanley Heptinstall, Robert G. Wilcox, Gary Peters, Mark Wickens, Håkan Emanuelsson, Paul Gurbel, Peer Grande, Christopher P. Cannon
Journal: Journal of the American College of Cardiology (2007)
Safety and Efficacy of Noninvasive Cardiac Pacing
Authors: Rodney H. Falk, Paul M. Zoll, Ross H. Zoll
Journal: New England Journal of Medicine (1983)

EXTERNAL cardiac pacing for asystole was introduced in 1952.1 Before then there was no effective method of restoring the heartbeat during complete heart block, and the annual mortality after a Stokes-Adams attack was 50 per cent. Although external cardiac pacing produced effective cardiac rhythm for prolonged periods, the associated stimulation of skin and skeletal muscle was painful and made recognition of cardiac responses difficult. With the development of transvenous approaches to cardiac pacing, this method was generally abandoned.Although temporary transvenous pacing is well tolerated by patients, it requires considerable skill and time for electrode insertion and is associated with . . .
Escherichia Coli Bacteremia in the Squirrel Monkey I. EFFECT OF COBRA VENOM FACTOR TREATMENT
Authors: David N. Gilbert, Jack A. Barnett, Jay P. Sanford
Journal: Journal of Clinical Investigation (1973)

Squirrel monkeys were significantly depleted of complement by a nontoxic protein constituent of cobra venom, and the influence of cobra factor (CoF) treatment on the course of Escherichia coli bacteremia was studied. Striking neutropenia occurred rapidly in control animals while the rate of occurrence of neutropenia was 20 to 30 times slower in the CoF-treated animals, suggesting that the E. coli-induced neutropenia was at least partially a complement-mediated response. In the CoF-treated monkeys, the initial rate of clearance of the E. coli from the circulation tended to be slower and the resultant levels of bacteremia were higher than in control animals. These observations are consistent with a hypothesis that complement-mediated neutrophilic leucocyte function is an important host defense mechanism in gram-ngeative bacillary bacteremia.
Dual function of MyD88 in RAS signaling and inflammation, leading to mouse and human cell transformation
Authors: Isabelle Coste, Katy Le Corf, Alain Kfoury, Isabelle Hmitou, Sabine Druillennec, Pierre Hainaut, Alain Eychene, Serge Lebecque, Toufic Renno
Journal: Journal of Clinical Investigation (2010)

Accumulating evidence points to inflammation as a promoter of carcinogenesis. MyD88 is an adaptor molecule in TLR and IL-1R signaling that was recently implicated in tumorigenesis through proinflammatory mechanisms. Here we have shown that MyD88 is also required in a cell-autonomous fashion for RAS-mediated carcinogenesis in mice in vivo and for MAPK activation and transformation in vitro. Mechanistically, MyD88 bound to the key MAPK, Erk, and prevented its inactivation by its phosphatase, MKP3, thereby amplifying the activation of the canonical RAS pathway. The relevance of this mechanism to human neoplasia was suggested by the finding that MyD88 was overexpressed and interacted with activated Erk in primary human cancer tissues. Collectively, these results show that in addition to its role in inflammation, MyD88 plays what we believe to be a crucial direct role in RAS signaling, cell-cycle control, and cell transformation.
Opera: Desire, Disease, Death
Authors: Richard E. Peschel
Journal: JAMA (1997)

The great opera masterpieces are among the most enduring artistic treasures in human history. Opera endures because it portrays universal human desires, experiences, and emotions. In live performance the best music and storytelling combine to produce a profound emotional and intellectual encounter. In<i>Opera: Desire, Disease, Death</i>, Linda and Michael Hutcheon have combined medical and musical history to produce a unique perspective "on illness and death as represented on the operatic stage of Europe and North America in the nineteenth and twentieth centuries." Illnesses, including tuberculosis, the plague, syphilis, cholera, and AIDS, are discussed in the context of operatic portrayals of their social importance and human suffering and of contemporary medical knowledge. In addition, a significant portion of the book is devoted to smoking. The authors successfully illustrate how the symbolic portrayal of disease and smoking changed in opera as more scientific knowledge was accumulated and disseminated throughout society.
Balloon-Protected Carotid Artery Stenting
Authors: Thilo Tübler, Michael Schlüter, Olaf Dirsch, Horst Sievert, Ilka Bösenberg, Eberhard Grube, Jürgen Waigand, Joachim Schofer
Journal: Circulation (2001)

Background Carotid artery stenting (CAS) has been advocated as an alternative to endarterectomy. To prevent cerebral atheroembolism during CAS, distal balloon occlusion of the target artery increasingly is employed during the procedure. A correlation of the size of captured particles with the incidence of periprocedural neurological complications (PNCs) has not been attempted. Methods and Results In a 4-center, phase-1 trial, 54 patients (46 men; age, 69±8 years) underwent 58 CAS procedures using the PercuSurge GuardWire system for distal protection. Aspirated debris was sent for histological/cytological analysis. Stent placement was successful in all cases. Mean balloon occlusion time was 10.4±4.0 minutes (range, 3.0 to 22.0 minutes). Three patients (5.2%) experienced PNCs: 1 prolonged reversible ischemic neurological deficit that resolved in ≤48 hours, 1 stroke, and 1 transient ischemic attack. Relevant particles (those with an area ≥10 000 μm 2 ) were found in 48 aspirates (83%). The median number of particles, their maximum diameter, and their maximum area were all significantly higher in the aspirates obtained during procedures associated with PNCs than in aspirates obtained during procedures not associated with PNCs. However, pronounced overlap in the distributions (PNCs versus no PNCs) of the number and maximum diameter of particles precluded any predictive inferences. In contrast, a maximum particle area &gt;800 000 μm 2 (&gt;0.8 mm 2 ) was associated with a 60% chance of having a PNC. Conclusions Despite balloon protection, PNCs occurred in 5.2% of patients who underwent CAS procedures. The maximum area of aspirated particles seems to be an indicator of increased risk for PNCs.