tbuckley/cabot-search huggingface dataset:
The Therapeutic Nightmare
Authors: Jean K. Weston
Journal: JAMA (1966)

Our first careful reading of<i>The Therapeutic</i><i>Nightmare</i><sup>1</sup>by Morton Mintz, undertaken when we were asked to review the book, resulted in amazed and pained unbelief. Allowing a week's interval for recovery, another careful reading only intensified our first impression. We found little recognizable as therapeutic—much as nightmare. There has been a surfeit in our time of ill-conceived (though sometimes clever) and inadequately researched publications on drugs (though presented with an aura of scientific and/or medical credibility); slanted (though paying minimal lip service to objectivity by choice of verbatim quotations from appropriately selected sources—in fact, such quotations from the Kefauver hearings make up a large percentage of Mintz's book); inferentially presented as "authoritative" (even if, in some cases, the identity of the "authorities" consulted must be kept "confidential"); arbitrarily and slyly indicting individuals and groups as consistently being in active and continuous collusion against the "public interest" (by stressing
Sensibility of the rectum to distension and the anorectal distension reflex in ulcerative colitis.
Authors: M J Farthing, J E Lennard-jones
Journal: Gut (1978)

The maximum volume of air tolerated within a rectal balloon was less in colitic patients than in normal subjects (P less than 0.001). Smaller volumes were tolerated by patients with a spontaneously bleeding mucosa than by those with less severe inflammation (P less than 0.001). Severe urgency of defaecation with incontinence was experienced by about half those with spontaneous mucosal haemorrhage but was infrequent among other colitics. Those patients with inactive colitis and a reduced maximum tolerable volume tended to have a smaller rectal size than those who could tolerate a normal volume within the rectum. Reflex relaxation of the internal anal sphincter on distension of the rectum appeared normal in patients with colitis.
Tyloxapol inhibits NF-kappa B and cytokine release, scavenges HOCI, and reduces viscosity of cystic fibrosis sputum.
Authors: A J Ghio, B C Marshall, J L Diaz, T Hasegawa, W Samuelson, D Povia, T P Kennedy, C A Piantodosi
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Cystic fibrosis (CF) patients develop progressive cytokine-mediated inflammatory lung disease, with abundant production of thick, tenacious, protease- and oxidant-rich purulent airway secretions that are difficult to clear even with physiotherapy. In the search for a potential treatment, we have tested tyloxapol, an alkylaryl polyether alcohol polymer detergent previously used as a mucolytic agent in adult chronic bronchitis. Tyloxapol inhibits activation of the transcription factor nuclear factor-kappa B (NK-kappa B), reduces resting secretion of the cytokine interleukin-8 (IL-8) in cultured human monocytes, and inhibits lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and the eiconsanoids thromboxane A2 and leukotriene B4 (LTB4). We have previously shown that tyloxapol is a potent antioxidant for hydroxyl radicals ( OH). Tyloxapol (0.05 to 0.1% wt/vol) effectively scavenges the oxidant hypochlorous acid (HOCl; 1 to 7.5 mM) in vitro, and protects from HOCl-mediated lung injury in rats. Tyloxapol also reduces the viscosity of CF sputum (from 463 +/- 133 to 128 +/- 52 centipoise). We conclude that tyloxapol is potentially useful as a new antiinflammatory therapy for CF lung disease, and could possibly promote clearance of secretions in the CF airway.
391. Effective Gene Therapy with Non-Integrating Lentivirus Vectors
Authors: Rafael J. Yáñez-Muñoz, Kamaljit S. Balaggan, Angus MacNeil, Alexander J. Smith, Prateek Buch, Steven Howe, Yanaí Durán, Robert E. MacLaren, Patrick N. Anderson, Christine Kinnon, Robin R. Ali, Adrian J. Thrasher
Journal: Molecular Therapy (2005)

Gene therapy strategies need to achieve efficient transgene expression whilst minimizing toxic effects. Retrovirus vectors are very effective in several systems, but they have been shown to cause malignancies through insertional mutagenesis, one of the most serious side-effects identified to date in pre-clinical studies and clinical trials. The risk of insertional mutagenesis has been considered unavoidable because no gene expression has been demonstrated in vivo in the absence of retroviral integration. However, retrovirus and lentivirus vectors can be rendered integration-defective by mutation in the integrase coding sequence. Following reverse transcription, mutant vectors fail to integrate and instead accumulate in transduced cells as double-stranded DNA circles. These circular forms are non-replicating but very stable and will persist if not diluted by cell division. Contrary to the results from previous in vivo studies, recent reports have shown efficient transgene expression in vitro from integration-deficient lentivirus vectors in post-mitotic and growth-arrested cells. These vectors also led to transient transgene expression or, in combination with episomal systems, to stable expression in proliferating cells in vitro. Given these developments we decided to re-evaluate the proficiency of integration-defective lentiviral vectors for in vivo expression in rodents. We now show that integration-deficient HIV-1 vectors lead to highly efficient, long-term marker gene expression in post-mitotic ocular and brain tissues. We also demonstrate efficient rescue in two rodent models of retinal degeneration, the Rpe65rd12/rd12 mouse and the Mertk-deficient Royal College of Surgeons (RCS) rat. The relevance of these studies for clinical application is highlighted by the fact that we have been able to transduce excised human retinal pigment epithelium with integration-deficient vectors. In conclusion, we demonstrate that integration-deficient HIV-1 vectors transduce post-mitotic tissues in vivo as efficiently as their integrating counterparts. For clinical applications in quiescent tissues these non-integrating vectors should virtually abolish the risk of insertional mutagenesis-induced malignancy.
CD59 incorporation protects hepatitis C virus against complement-mediated destruction
Authors: Tohti Amet, Marwan Ghabril, Naga Chalasani, Daniel Byrd, Ningjie Hu, Ayslinn Grantham, Ziqing Liu, Xuebin Qin, Johnny J. He, Qigui Yu
Journal: Hepatology (2011)

Several enveloped viruses including human immunodeficiency virus type 1 (HIV-1), cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), Ebola virus, vaccinia virus, and influenza virus have been found to incorporate host regulators of complement activation (RCA) into their viral envelopes and, as a result, escape antibody-dependent complement-mediated lysis (ADCML). Hepatitis C virus (HCV) is an enveloped virus of the family Flaviviridae and incorporates more than 10 host lipoproteins. Patients chronically infected with HCV develop high-titer and crossreactive neutralizing antibodies (nAbs), yet fail to clear the virus, raising the possibility that HCV may also use the similar strategy of RCA incorporation to escape ADCML. The current study was therefore undertaken to determine whether HCV virions incorporate biologically functional CD59, a key member of RCA. Our experiments provided several lines of evidence demonstrating that CD59 was associated with the external membrane of HCV particles derived from either Huh7.5.1 cells or plasma samples from HCV-infected patients. First, HCV particles were captured by CD59-specific Abs. Second, CD59 was detected in purified HCV particles by immunoblot analysis and in the cell-free supernatant from HCV-infected Huh7.5.1 cells, but not from uninfected or adenovirus serotype 5 (Ad5) (a nonenveloped cytolytic virus)-infected Huh7.5.1 cells by enzyme-linked immunosorbent assay. Last, abrogation of CD59 function with its blockers increased the sensitivity of HCV virions to ADCML, resulting in a significant reduction of HCV infectivity. Additionally, direct addition of CD59 blockers into plasma samples from HCV-infected patients increased autologous virolysis.Our study, for the first time, demonstrates that CD59 is incorporated into both cell line-derived and plasma primary HCV virions at levels that protect against ADCML. This is also the first report to show that direct addition of RCA blockers into plasma from HCV-infected patients renders endogenous plasma virions sensitive to ADCML.
NHS patients who do not want their information shared will have to opt out of IT system
Authors: Michael Cross
Journal: BMJ (2006)

Leaders of the NHS information technology (IT) programme said last week that they will stick to a controversial policy on patients' consent. The policy will require that patients who do not want their data on the new system to be shared to actively opt out.

Mike Pringle, one of the programme's clinical leads, said last week that the alternative “opt in” policy proposed by the BMA's General Practitioners Committee would jeopardise the quality of care.

However, in response to concerns about confidentiality the leaders …
Letter: Starving children before operation.
Authors: E N Fry, A A Ibrahim
Journal: BMJ (1974)

tical solution.Mr. Illich foresees a cata- clylmic collapse of our present institutionalized values and Dr. Bradshaw envisages a similar end.One would like to think that this particular era of La condition humaine will end "not with a bang but with a sigh."There may be many small but vital pockets of hope and resistance standing out in the Western world.Let us hope that some of these have among their numtber "men of medicine."-Iam, etc.,
Canada tries once more to set public health goals
Authors: Barbara Kermode-Scott
Journal: BMJ (2005)

Canada's latest attempt to set up nationwide goals for public health was on the agenda at the annual meeting of the Canadian Medical Association in Edmonton, Alberta, this week.

In the past 30 years various efforts have been made to develop health goals for Canada, but none reached fruition.

Doctors from across Canada gathered at the meeting to learn why hope is now renewed for a plan to improve the length and quality of life of Canadians and eliminate health inequalities.

Canada is a big country with some serious challenges (such as differences in access to …
Time on the Gulf of Mexico
Authors: Joshua Latzman
Journal: Annals of Internal Medicine (2007)

Ad Libitum7 August 2007Time on the Gulf of MexicoJoshua LatzmanJoshua LatzmanFrom Manhasset, NY 11030.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-3-200708070-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail As peaceful air ravaged the tranquil slumberocean swells fell on primitive smoothtungsten shells which melt the time,churn the tide as my cracked lips fell on herdelicate shell—smooth, pure, subordinate.Melt the day for the time the grainsscattered like infinitesimal rain, infinite likethe wake of a ship sailing seaward orthe mangrove leaf soaring upwardtwirling ever through a torrent night.Something kind and gentle about theebbs and flows a gulf wind brings sendsdistant worlds ... Author, Article, and Disclosure InformationAffiliations: From Manhasset, NY 11030.Current Author Address: Joshua Latzman, MD, 321 Thompson Shore Road, Manhasset, NY 11030. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 August 2007Volume 147, Issue 3Page: 210KeywordsThorax ePublished: 7 August 2007 Issue Published: 7 August 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Treatment of Chronic Depression
Authors: Jeffrey E. Kelsey
Journal: JAMA (1996)

To the Editor.  —Dr Goodwin 1 raises numerous important points concerning the intricacies of managing depression in an era of increased managed care. However, Goodwin's suggestions for pharmacotherapy were somewhat surprising. Mr N apparently showed a partial response to imipramine, but did not do well on fluoxetine; we are unclear as to his response to bupropion. It also appears that Mr N's medications will have to be managed to a certain extent by his primary care physician.  Given this, the rationale is not clear for retrying bupropion and then engaging in augmentation therapy, which is usually not a part of routine primary care practice. A different approach would be to try venlafaxine as a first choice, rather than as a second- or third-line agent, since it is a mixed reuptake inhibitor 2 like imipramine, but as Goodwin mentioned, has a favorable adverse effect profile. This approach also would simplify treatment
A prospective study of large vs. small burrs: Intravascular ultrasound findings in the coronary angioplasty and rotablator atherectomy trial (CARAT)
Authors: Barry M. Kaplan, Richard E. Stewart, Venu M. Reddy, William W. O'Neill, Cindy L. Grines, Keith H. Benzuly, Robert D. Safian
Journal: Journal of the American College of Cardiology (1996)
A man with a mass in the thigh
Authors: R. Bodington, P. R. W. Stanley
Journal: BMJ (2014)

A 54 year old man presented to his general practitioner because of a fullness in his left lateral thigh that he first noticed while playing golf, although it was not related to an identifiable injury. He had a history of hypertension and fibromyalgia and was taking atenolol, ramipril, pregabalin, and tramadol but was otherwise well. The GP thought that the swelling was caused by a muscular injury, but the patient re-presented four months later because the mass had grown from a small bump to a swelling of 8 cm in diameter. It was also beginning to cause some knee stiffness but no pain. On examination he had a large firm swelling in his lateral thigh. On this occasion his GP referred him on a two week wait to the regional plastic surgery department. An ultrasound scan showed a 6 × 8 cm intramuscular mass with cystic changes and patchy neovascularity, but no inguinal or pelvic lymphadenopathy. Ultrasonography was followed by magnetic resonance imaging, with and without gadolinium contrast (fig 1⇓). 



Fig 1 Magnetic resonance imaging scan with gadolinium contrast 





### 1. What is the differential diagnosis?

#### Short answer

Benign causes of a large lump in an extremity include haematoma, chronic muscle tear, an abscess, and lipoma. Malignant causes include sarcoma, lymphoma, and soft tissue metastasis from an occult tumour.

#### Long answer

This mass could be malignant or benign. Benign soft tissue lumps outnumber malignant ones in a ratio of at least 100:1.1 Benign causes of a large lump in the extremity include haematoma, chronic muscle tear, an abscess, and lipoma. In this case, the long slow growth pattern with no history of trauma make haematoma and a …
Assisted Ventilation of the NeonateAssisted Ventilation of the Neonate
Authors: Tiffany L. Brainerd
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Ketanserin in the treatment of Raynaud's phenomenon associated with generalized scleroderma
Authors: M. ENGELHART
Journal: British Journal of Dermatology (1988)

The efficacy of the 5‐HT‐2‐receptor antagonist, ketanserin, in the treatment of Raynaud's phenomenon was assessed in a double‐blind, placebo‐controlled, crossover trial in nine patients with generalized scleroderma (GS). Each patient received ketanserin 20 mg or placebo three times a day in the 1st week and 40 mg ketanserin or placebo three times a day for the remaining 4 weeks, and was then crossed over for 5 weeks. Measurements were made of finger blood pressure and flow during a cold challenge test and patients recorded numbers of Raynaud's attacks. No significant improvement was found in reactions to cold provocation or in numbers of Raynaud's attacks during ketanserin treatment, but intolerable side‐effects were common. Interactions with concomitant medication might be a possible explanation for this. We conclude that ketanserin in the dose given, is not effective in the treatment of Raynaud's phenomenon in GS.
Fetal cardiac morphology of tetralogy of Fallot with absent pulmonary valve in the rat.
Authors: K Momma, M Ando, A Takao
Journal: Circulation (1990)

Fetal in situ cardiovascular and bronchial morphologies were studied in rats with tetralogy of Fallot and absent pulmonary valve to clarify the prenatal pathology of this complex. There were 42 fetal rats with this complex among 300 fetuses treated with N,N'-bis-(dichloroacetyl)-1,8-octamethylenediamine (bis-diamine) (200 mg) on the 10th day of pregnancy. After undergoing rapid whole-body freezing on the 21st day, they were studied by means of serial cross-sectional photographs of the frozen thorax. Fetuses with normal heart treated with bis-diamine served as control. Tetralogy of Fallot and absent pulmonary valve in the fetus was associated with absence of the ductus arteriosus, enlargement and hypertrophy of both ventricles, and enlargement of the pulmonary arteries that compressed the bronchial trees. These abnormalities were inversely correlated with the degree of pulmonary stenosis. Milder stenosis (pulmonary valve ring greater than 50% of control, n = 28) was associated with larger pulmonary arteries (250 +/- 12% of control) (mean +/- SEM) and larger ventricles (volume, 200 +/- 15%; mass, 130 +/- 4%). Severe stenosis (pulmonary valve ring less than 50% of control, n = 14) was associated with mildly enlarged pulmonary arteries and mild bronchial compression. We concluded that enlargement of the pulmonary arteries and bronchial compression develop in fetal life and are associated with mild pulmonary stenosis in tetralogy of Fallot and absent pulmonary valve.
Efficacy and Safety of Imatinib Mesylate in Advanced Gastrointestinal Stromal Tumors
Authors: George D. Demetri, Margaret von Mehren, Charles D. Blanke, Annick D. Van den Abbeele, Burton Eisenberg, Peter J. Roberts, Michael C. Heinrich, David A. Tuveson, Samuel Singer, Milos Janicek, Jonathan A. Fletcher, Stuart G. Silverman, Sandra L. Silberman, Renaud Capdeville, Beate Kiese, Bin Peng, Sasa Dimitrijevic, Brian J. Druker, Christopher Corless, Christopher D.M. Fletcher, Heikki Joensuu
Journal: New England Journal of Medicine (2002)

Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors.
I and II generation anti-HCV testing in thalassemic patients
Authors: G. Taliani, R. Lecce, M.C. Badolato, A. Vania, M.C. Aliquò, S. Maiozzi, G. Nigro, R. Bruni, G. Poliandri, A. Bozza, C. De Bac
Journal: Journal of Hepatology (1991)
Letter: Facial flushing in acute pancreatitis.
Authors: C W Imrie
Journal: BMJ (1974)

E.B. virus, like other viruses, sometimes does produce lymphomas in animals.I would not be frightened by the prospect of developing infectious mononucleosis after E.B. virus in- oculation and I would discount the danger of developing a Burkitt tumour in the short span of life left to me.The question I would regard as of the utmost importance to me is whether, by E.B. virus inoculation, my tumour could be made once more drugsensitive.The answer to this question is un- known but could, like many another scienti- fic problem, be elucidated by being put to the test.-I am, etc.,
Maintenance of Therapeutic Phenytoin Plasma Levels via Intramuscular Administration
Authors: DONALD PERRIER
Journal: Annals of Internal Medicine (1976)

A parenteral dosing regimen was designed for the immediate attainment and maintenance of therapeutic plasma levels of Phenytoin in patients requiring anticonvulsant therapy, but not able to tolerate oral medication. An intravenous dose of 10.7 mg/kg body weight infused at a rate of 25 mg/min immediately followed by an intramuscular dose of 12.7 mg/kg body weight were administered initially. This was followed by daily intramuscular maintenance doses, generally 8.6 mg/kg body weight, until oral medication could be tolerated. Due to variability between subjects, primarily in metabolism, the predicted maintenance doses had to be adjusted in approximately one third of the patients. This regimen for the dosing of Phenytoin was evaluated in 98 patients and consistently yielded therapeutic levels.
Sun Exposure, Vitamin D Receptor Genetic Variants, and Risk of Breast Cancer in the Agricultural Health Study
Authors: Lawrence S. Engel, Jaya Satagopan, Camelia S. Sima, Irene Orlow, Urvi Mujumdar, Joseph Coble, Pampa Roy, Sarah Yoo, Dale P. Sandler, Michael C. Alavanja
Journal: Environmental Health Perspectives (2013)

Background: Epidemiologic evidence suggests a negative relation between sunlight exposure and breast cancer risk. The hypothesized mechanism is sunlight-induced cutaneous synthesis of vitamin D.Objectives: Our goal was to examine sun exposure and its interaction with vitamin D receptor (VDR) gene variants on breast cancer risk.Methods: We examined sun exposure and breast cancer incidence among 31,021 private pesticide applicators’ wives, including 578 cases, enrolled in the prospective Agricultural Health Study cohort and followed 8.6 years on average. We estimated interactions between sun exposure, VDR variants, and breast cancer in a nested case–control study comprising 293 cases and 586 matched controls. Information on sun exposure was obtained by questionnaire at cohort enrollment. Relative risks were estimated using Cox proportional hazards regression for the cohort data and conditional logistic regression for the nested case–control data.Results: We observed a small decrease in breast cancer risk in association with usual sun exposure of ≥ 1 hr/day (versus &lt; 1 hr/day) 10 years before the start of follow-up among all participants [hazard ratio (HR) = 0.8; 95% CI: 0.6, 1.0]. The association appeared to be slightly stronger in relation to estrogen receptor–positive tumors (HR = 0.7; 95% CI: 0.5, 0.9) than estrogen receptor–negative tumors (HR = 1.1; 95% CI: 0.6, 2.1). The HR for joint exposure ≥ 1 hr/day of sunlight and one VDR haplotype was less than expected given negative HRs for each individual exposure (interaction p-value = 0.07).Conclusion: Our results suggest that sun exposure may be associated with reduced risk of breast cancer, but we did not find clear evidence of modification by VDR variants. Larger studies are warranted, particularly among populations in whom low levels of usual sun exposure can be more precisely characterized.Citation: Engel LS, Satagopan J, Sima CS, Orlow I, Mujumdar U, Coble J, Roy P, Yoo S, Sandler DP, Alavanja MC. 2014. Sun exposure, vitamin D receptor genetic variants, and risk of breast cancer in the Agricultural Health Study. Environ Health Perspect 122:165–171; http://dx.doi.org/10.1289/ehp.1206274