tbuckley/cabot-search huggingface dataset:
Nanocapsule-delivered Sleeping Beauty mediates therapeutic Factor VIII expression in liver sinusoidal endothelial cells of hemophilia A mice
Authors: Betsy T. Kren, Gretchen M. Unger, Lucas Sjeklocha, Alycia A. Trossen, Vicci Korman, Brenda M. Diethelm-Okita, Mark T. Reding, Clifford J. Steer
Journal: Journal of Clinical Investigation (2009)

Liver sinusoidal endothelial cells are a major endogenous source of Factor VIII (FVIII), lack of which causes the human congenital bleeding disorder hemophilia A. Despite extensive efforts, gene therapy using viral vectors has shown little success in clinical hemophilia trials. Here we achieved cell type-specific gene targeting using hyaluronan- and asialoorosomucoid-coated nanocapsules, generated using dispersion atomization, to direct genes to liver sinusoidal endothelial cells and hepatocytes, respectively. To highlight the therapeutic potential of this approach, we encapsulated Sleeping Beauty transposon expressing the B domain-deleted canine FVIII in cis with Sleeping Beauty transposase in hyaluronan nanocapsules and injected them intravenously into hemophilia A mice. The treated mice exhibited activated partial thromboplastin times that were comparable to those of wild-type mice at 5 and 50 weeks and substantially shorter than those of untreated controls at the same time points. Further, plasma FVIII activity in the treated hemophilia A mice was nearly identical to that in wild-type mice through 50 weeks, while untreated hemophilia A mice exhibited no detectable FVIII activity. Thus, Sleeping Beauty transposon targeted to liver sinusoidal endothelial cells provided long-term expression of FVIII, without apparent antibody formation, and improved the phenotype of hemophilia A mice.
Remarks on Fractures of the First Cervical Vertebra
Authors: G. Jefferson
Journal: BMJ (1927)

IN a previous paper I described at some length the patlho-!logical anatomy, mechanism, and symptomatology of frac- tures of the atlas vertebrae.Having now three more recent examples of this injury to add to the four published tlhen, Imay take this opportuniity of bringing the hlistor-y of the subject up to date, anid of making such amplifica- tions or amenidments as further experience seems to demanid.The w-liole question of atlas fractuire is, in reality, indis- solubly bound up with thematter of injuries to thie occipitoatlanto-axial component of the vertebral column, both bones and ligaments.I shall be compelled by thenecessary limits of space to confine my observations strictly to the atlas, and will hlaxve to reserve for another occasion the many fields through which a fascinating subjectmight well tempt us to wanlder.So much that is dramatic but untrue, so much tlhat is interesting yet founded on legend, obscures the facts in this corner of suirgery that it is imipossible to take ul) the thriead of the narrative in moderl i tirr.es.A complete surv ey of the history of thlo various lesions is required before we can go forward along a sure pat}}.As regards atlantal injury I have previously sketched in the necessary-background, but will once more outline tIme chief features after describing the new cases. MATERIAL.In 1920 I described four examples of atlas fracture- two clinical examples and two museum sl)ecimens--and collected forty-two other cases from the literature.I have omitted cases of gunshot injury in the present conmmuniication.The total material, personal anid otherwise, n1ow amouints to sixty-five cases.I am indebted to Dr. Arniison anid Dr. Forbes for two of them (see Tables I and11).CASE i.-Fracture of the Posterior Arch of the Atla(s.A man, aged 57, was sent to see me in 1920,.somo five months after an accident which had left his neck very painful and stiff.He was unable to describe the exact facts, but was drawing water in a slightly stooping position when a telegraph pole, blown over by the wind, struck him on the back of the head.The scalp was not cut, there was no bleeding from the nose, mouth, or ears.He was stunned for a short time and when he became conscious he had great pain in the neck, in ,1/ the shoulders, and in the arms as bed for eight weeks.His arms, he ///'/'////B/ \ said, were still weak so that he could IK0///X/, \ not raise them hiigh above his head or get his hands easily into his trouser pockets.He had had no ////,.Zi tiSi difficulty in walking.The outstand- ing feature of the case had been the -.X,;zjy//J% > pain in the occipital i-egion of the scalp, and although thlis was im- proving, it was still very tr oublesome-so muclh so, indeed, that he
REPEATED SUCCESSFUL AORTIC EMBOLECTOMY
Authors: Herbert E. Gude
Journal: JAMA (1960)

Without surgical intervention the catastrophe of aortic bifurcation or saddle embolus results in an immediate mortality of 75%, but surgical removal of the embolus within 6 to 10 hours will usually restore the arterial flow. Embolism implies serious systemic disease. Although most patients survive aortic embolectomy, few of them are alive after five years. They die subsequently from further embolic episodes or from cardiac failure. <h3>Previous Reports</h3> Bauer performed the first successful aortic embolectomy in 1913. In 1943, McClure and Harkins,<sup>1</sup>in a review of the literature, reported that 21 aortic emboli had been successfully removed. Thiessen and Marxen,<sup>2</sup>in 1952, reported that 34 successful aortic embolectomies had been performed, and by 1958 Dale and Mahoney<sup>3</sup>had counted 64 successful embolectomies at the bifurcation. Since 1958 six more reports of this operation have appeared in the literature. With the advancements in arterial surgery, it is probable that
Computerized Axial Tomography in Syringomyelia
Authors: Giovanni Di Chiro, Stewart P. Axelbaum, Dieter Schellinger, Homer L. Twigg, Robert S. Ledley
Journal: New England Journal of Medicine (1975)

The ACTA-scanner, a device for computerized axial tomography, permits cross-sectional radiographic study of the entire human body, including the spine. In the ACTA-scan, the spinal cord appears as a roundish formation surrounded by the less dense subarachnoidal cerebrospinal fluid. The spines of 18 patients with verified (nine cases) or suspected (nine cases) syringomyelia were studied by ACTA-scanning. In seven of the verified and in four of the nonverified cases, some evidence of cord cavitation was shown. The cystic part of a cervical-cord ependymoma was also demonstrated. ACTA-scanning is an easily performed, noninvasive, innocuous procedure. This technic, which complements other radiographic methods of evaluating the spinal cord, is particularly suitable for screening and follow-up study of patients with syringomyelia. The easily accomplished recognition of a possible associated hydrocephalus is an added advantage of ACTA-scanning.
The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives
Authors: Andre F. Carvalho, Michael Berk, Thomas N. Hyphantis, Roger S. McIntyre
Journal: Psychotherapy and Psychosomatics (2014)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Major depressive disorder is a prevalent and disabling illness. Notwithstanding numerous advances in the pharmacological treatment of depression, approximately 70% of patients do not remit after first-line antidepressant treatment. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; The MEDLINE/PubMed, EMBASE and ClinicalTrials.gov electronic databases were searched from inception to October 1, 2013, for randomized controlled trials (RCT), relevant open-label trials, meta-analyses and ongoing trials of pharmacological and psychotherapeutic approaches to treatment-resistant depression (TRD). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Switching to a different antidepressant is a useful option following nonresponse to a first-line agent. Although widely used in clinical practice, there is limited evidence to support antidepressant combination for TRD. Notwithstanding evidence for lithium or T&lt;sub&gt;3&lt;/sub&gt; augmentation to be successful in TRD, most studies were carried out when participants were treated with tricyclic antidepressants (TCA). Of the available strategies to augment the response to new-generation antidepressants, the use of some atypical antipsychotics is best supported by evidence. Several novel therapeutic options are currently discussed. Evidence suggests that cognitive therapy (CT) is an effective strategy for TRD. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The success of switching to a different antidepressant following a first-line agent is supported by evidence, but there is limited evidence for effective combination strategies. Lithium and T&lt;sub&gt;3&lt;/sub&gt; augmentation of TCA have the strongest evidence base for successful treatment of TRD. The use of augmentation of newer-generation antidepressants with atypical antipsychotics is supported by a growing evidence base. Current evidence supports CT as an effective strategy for TRD. There is a need for additional large-scale RCT of TRD. The development of new antidepressants targeting novel pathways opens a promising perspective for the management of TRD.
ON THE COLLAPSE OF BACTERIAL ENDOTOXIN RESISTANCE FOLLOWING HEMORRHAGE
Authors: Sheldon E. Greisman
Journal: The Journal of Experimental Medicine (1960)

Unanesthetized immature albino rabbits exposed to 2 hours of severe but reversible hemorrhagic shock induced with aseptic precautions by multiple cardiac bleedings exhibited no increase in susceptibility to single intravenous injections of 200 microg./kg. E. coli endotoxin administered 4 hours post retransfusion, a quantity of endotoxin that was found to be the largest dose uniformly non-lethal to normal rabbits. Paired and randomly selected rabbits treated identically except for the additional procedure of a femoral arterial cutdown and ligation (without aseptic precautions) exhibited increases in susceptibility to the same endotoxin of several hundredfold. This effect could not be attributed to the femoral cutdown and arterial ligation alone since such trauma when coupled with sham cardiac bleedings failed to increase susceptibility to 200 microg./kg. of endotoxin. These data appear valid since sham cardiac bleedings produced no detectable impairment of myocardial contractility, while 2 hours of hemorrhagic shock at 50 mm. Hg with the Lamson reservoir technique caused an increase in endotoxin susceptibility comparable to that seen when cardiac bleedings were combined with a non-sterile femoral arterial cutdown and ligation. The mechanisms increasing the susceptibility to E. coli endotoxin were investigated. It was found that (a) rabbit femoral skeletal muscle is normally contaminated with clostridia, (b) the use of aseptic femoral wounding precautions exerted some suggestive protective influence, (c) the use of aseptic wounding precautions combined with immediate topical sulfanilamide and wound closure exerted a significant protective influence, and (d) prophylactic polyvalent gas gangrene antitoxin protected in a manner not demonstrable when diphtheria antitoxin was employed as a control. These observations suggest that clostridial wound infection is one mechanism whereby a femoral arterial cutdown lowers endotoxin resistance of the rabbit following hemorrhagic shock. It is, however, not the only mechanism since the ligation of a femoral artery during hemorrhagic shock led to edema following retransfusion equivalent to a mean of approximately 30 per cent of the original circulating plasma volume. The intensification of shock caused by this transudation presumably intensified reticulo-endothelial injury, and thus further lowered the resistance of the rabbit to an intravenous injection of endotoxin 4 hours following retransfusion.
Abnormal megakaryocyte development and platelet function in Nbeal2−/− mice
Authors: Walter H. A. Kahr, Richard W. Lo, Ling Li, Fred G. Pluthero, Hilary Christensen, Ran Ni, Nima Vaezzadeh, Cynthia E. Hawkins, Andrew S. Weyrich, Jorge Di Paola, Carolina Landolt-Marticorena, Peter L. Gross
Journal: Blood (2013)
Sleep related vehicle accidents
Authors: C C H Cook, I P Albery
Journal: BMJ (1995)

differing natural courses,' and their inclusion could require intolerable variations in manage- ment.The hospice environment may seem more dis- tressing for patients with diseases other than cancer; moreover, if such patients were treated in hospices, patients with cancer might have greater difficulties with body image and in accepting the inconsistency of more active management being given for non-malignant diseases.5Hospices are deliberately not generally equipped to deliver such management so that overmedicalisation of terminal care is avoided.Presently hospices see only about half of patients with cancer, which leaves little scope for the needs of a wider population (estimated at 150% extra bed days required for patients with diseases other than cancer6).Hospice-style input for non-malignant diseases remains equally important but requires appro- priate provision in addition to traditional hospices.Adequate community services could also meet much of this need.Hospices offer quality rather than quantity and should not be seen as an easy and cheaper option for providing care for patients with terminal disease as if they were a homogeneous group.
Direct evidence for presence of Ph-1 chromosome in erythroid cells.
Authors: J. M. Rastrick, P. H. Fitzgerald, F. W. Gunz
Journal: BMJ (1968)

the present patient the daily output of potassium in the faeces represented one-half of the total sensible loss of potassium from the body. SummaryIn a patient with primary hyperaldosteronism the rates of net transport and of unidirectional fluxes of sodium, potassium, and water in the intact colon were measured before and after removal of the adrenocortical turnour, by perfusing the colon with an isotopically labelled test solution introduced into the caecum through a tube passed by mouth.The results in this patient were compared with those in eight control subjects.Before removal of the aldosterone-producing turnour the colon of the patient secreted potassium at four to five times the rate in control subjects.The unidirectional flux of potassium into the colonic lumen was greatly enhanced and the daily loss of potassium in the faeces increased.The rates of potassium transport returned to within the range observed in control subjects after the removal of the tumour.
Glasgow gang members offered way out of violent lifestyle
Authors: Z. Kmietowicz
Journal: BMJ (2008)

Strathclyde police have launched a scheme that they hope will see up to 500 young men reject gang violence in Glasgow’s east end. 

Under the initiative, men who promise to give up their gang membership are given the chance of a new life—a personal care worker along with access to health services, education, careers’ advice, leisure and other diversion activities, and housing. 

The £5m (€6m; $7m) initiative, which is funded by the Scottish government, is based on the Cincinnati Ceasefire …
Rupture of Diaphragm
Authors: H. L. Laws, M. L. Waldschmidt
Journal: JAMA (1980)

<h3>To the Editor.—</h3> We appreciated the article (241:1929, 1979) entitled "Isolated Rupture of the Right Hemidiaphragm With Eventration of the Liver," by Neal W. Salomon, MD, and Charles F. Zukoski, MD, and believe that it does seem to emphasize an important diagnosis—rupture of the right diaphragm. In recent scrutiny of our patients, we noted rupture of the right diaphragm to be as frequent as rupture of the left diaphragm inblunt injury. In two other recent articles, the disparity was also small (Table). The group from Minnesota' found peritoneal lavage to be highly inaccurate in the diagnosis of diaphragmatic rupture, as noted by Salomon and Zukoski in their patients.
Reported euthanasia cases in Hollnd fall for second year
Authors: T. Sheldon
Journal: BMJ (2002)

For the second year running, Dutch doctors have reported fewer cases of euthanasia and assisted suicide, raising questions over whether mercy killing is declining or doctors are failing to fulfil their legal obligation to notify the authorities.

In 2001 the five regional euthanasia assessment committees received 2054 reports, compared with 2216 in 1999.

The committees, comprising a doctor, a lawyer, and an ethicist, replaced the system of reporting to a local magistrate in 1998. This followed a national study of euthanasia in 1995 that estimated that the 1466 …
Legacies of Nuremberg. Medical ethics and human rights
Authors: M. A. Grodin
Journal: JAMA (1996)

The 50th anniversary of the Doctors Trial at Nuremberg provides an important opportunity to reflect on its legacy to both medical ethics and human rights. While many contemporary physicians view medicine's involvement in Nazi Germany as of only historical interest, the articles by Katz, 1 Sidel, 2 Barondess, 3 Faden et al, 4 Harkness, 5 Sonis et al, 6 and Seidelman 7 eloquently demonstrate that there is much we can learn by confronting the crimes committed by the Nazi physicians.  After World War II, the Allies prosecuted the major surviving Nazi war criminals in an international military tribunal before judges from the United States, the United Kingdom, France, and the former Soviet Union. That trial resulted in making new international law and can properly be seen, together with the promulgation of the 1948 Universal Declaration of Human Rights, as the birth of the international human rights movement. The trial
816-5 Progression of coronary artery disease in diabetics demonstrated by single isotope rest/stress Tc-99m sestamibi myocardial perfusion imaging: More rapid than nondiabetics?
Authors: Gavin L Noble, Sachin M Navare, Syed A Hussain, Deborah M Katten, Alan W Ahlberg, Jacob Calvert, William E Boden, Gary V Heller
Journal: Journal of the American College of Cardiology (2004)
BLASTOMYCOSIS AND THE BLASTOMYCOSIS-LIKE INFECTIONS
Authors: LESLIE M. SMITH
Journal: JAMA (1941)

The clinical entity known since 1894 as Gilchrist's disease or American blastomycosis has usually been thought of as a mycologic entity as well. The subject has been complicated, however, by the incrimination of a number of different fungi as the causes of quite similar lesions. It seems best, as Benham<sup>1</sup>has suggested, to reserve the name blastomycosis for lesions caused by the species of fungus described by Gilchrist and named Blastomyces dermatitidis and to apply appropriate names to the other somewhat similar diseases caused by other species of fungi. The latter may be collectively designated as the blastomycosis-like infections. This term will be applied here to the mycotic granulomas in which yeastlike cells are found, whether or not they are characterized by budding. My purpose in this paper is to present these more or less similar diseases as a group and to emphasize their similarity and the importance of
Case 25-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Bernard M. Jacobson, Thomas McC. Chesney
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 65-year-old man was admitted to the hospital because of ascites.Ten years previously a pre-employment physical examination revealed a barrel chest and dorsal scoliosis, without other abnormality. The patient was well until three years before admission, when he went to his physician because of a back strain and was found to have polycythemia. He was referred to this hospital, where examination revealed mild plethora and minimal cyanosis. The edge of the liver was felt at the right costal margin, and the splenic tip was palpable. The hematocrit was 61 per cent, the white-cell count 14,550, and . . .
Global Theme Issue on Poverty and Human Development
Authors: Annette Flanagin, Margaret A. Winker
Journal: JAMA (2007)

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Vesnarinone Prolongs Action Potential Duration Without Reverse Frequency Dependence in Rabbit Ventricular Muscle by Blocking the Delayed Rectifier K <sup>+</sup> Current
Authors: Junji Toyama, Kaichiro Kamiya, Jianhua Cheng, Jong-Kook Lee, Ryoko Suzuki, Itsuo Kodama
Journal: Circulation (1997)

Background Methanesulfonanilide derivatives, selective inhibitors of the rapidly activating component ( I Kr ) of the delayed rectifier potassium current ( I K ), prolong action potential duration (APD) of cardiac muscles with reverse frequency dependence, which limits their clinical use because of proarrhythmia. Vesnarinone, a quinolinone derivative developed as a cardiotonic agent, has complex pharmacological properties, but its clinical efficacy is explained in part by I K reduction. Therefore, we investigated the mode of I K block by vesnarinone. Methods and Results I K of the rabbit ventricular myocyte was activated by voltage-clamp steps applied from a holding potential to various depolarizing levels. The development of I K block at depolarization (+10 mV) and its recovery process at hyperpolarization (−75 mV) were compared between vesnarinone and E-4031. The I K block by vesnarinone (3 μmol/L) developed and recovered monoexponentially, with time constants of 361 ms (n=5) and 1.87 seconds (n=4), respectively. I K block by E-4031 (0.3 μmol/L) developed instantaneously, with no recovery from the block at hyperpolarization. The I K block by vesnarinone, estimated by I K tail after a train of depolarizing pulses (for 30 seconds at 0.2 to 2 Hz), was increased with increasing frequency (twofold at 2 from 0.2 Hz), but that by E-4031 was unchanged. In rabbit papillary muscles, vesnarinone (10 μmol/L) prolonged APD at stimulation frequencies &gt;0.2 Hz, whereas E-4031 (0.3 μmol/L) prolonged that in a reverse frequency-dependent manner. Conclusions Vesnarinone may prolong the repolarization of human cardiac muscle without reverse frequency dependence, because I Kr is expressed in humans as well as in the rabbit. Thus, this drug may be a model for an ideal class III drug without the risk of proarrhythmia.