tbuckley/cabot-search huggingface dataset:
Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient<i>PEX2</i>Zellweger mice
Authors: Megan H. Keane, Henk Overmars, Thomas M. Wikander, Sacha Ferdinandusse, Marinus Duran, Ronald J. A. Wanders, Phyllis L. Faust
Journal: Hepatology (2007)

The marked deficiency of peroxisomal organelle assembly in the PEX2(-/-) mouse model for Zellweger syndrome provides a unique opportunity to developmentally and biochemically characterize hepatic disease progression and bile acid products. The postnatal survival of homozygous mutants enabled us to evaluate the response to bile acid replenishment in this disease state. PEX2 mutant liver has severe but transient intrahepatic cholestasis that abates in the early postnatal period and progresses to steatohepatitis by postnatal day 36. We confirmed the expected reduction of mature C24 bile acids, accumulation of C27-bile acid intermediates, and low total bile acid level in liver and bile from these mutant mice. Treating the PEX2(-/-) mice with bile acids prolonged postnatal survival, alleviated intrahepatic cholestasis and intestinal malabsorption, reduced C27-bile acid intermediate production, and prevented older mutants from developing severe steatohepatitis. However, this therapy exacerbated the degree of hepatic steatosis and worsened the already severe mitochondrial and cellular damage in peroxisome-deficient liver. Both untreated and bile acid-fed PEX2(-/-) mice accumulated high levels of predominantly unconjugated bile acids in plasma because of altered expression of hepatocyte bile acid transporters. Significant amounts of unconjugated bile acids were also found in the liver and bile of PEX2 mutants, indicating a generalized defect in bile acid conjugation.Peroxisome deficiency widely disturbs bile acid homeostasis and hepatic functioning in mice, and the high sensitivity of the peroxisome-deficient liver to bile acid toxicity limits the effectiveness of bile acid therapy for preventing hepatic disease.
Website of the week: Asylum seekers
Authors: D. Carnall
Journal: BMJ (2000)

This week the BMJ considers the health of asylum seekers, which, unsurprisingly, is problematic. “There is no greater loss on earth than the loss of one's native land.” So begins the site of the United Nations High Commissioner for Refugees (www.unhcr.ch/), with a quote from Euripides. Not having read Euripides in the original (though of course, there's nothing to stop me: classics.mit.edu/Browse/browse-Euripides.html) I don't know whether this was a reference to the experience of exile or displacement from agricultural land.

In Britain, the contemporary debate is dominated by the distinction between “economic migrants” and “genuine refugees.” Access to the economic literature that lies behind the jargon lies at ideas.uqam.ca/ideas/data/JEL/F22.html. Few of the articles are available in full text, but just skimming the titles and abstracts is informative. Migrants invest in “language capital” and lead transnational lives.

Officials who attempt to make the distinction between migrant and refugee no doubt have a difficult task, but Britain's current policies are explained on a well designed Home Office site (www.homeoffice.gov.uk/ind/asylum/asylum_home.html), which explains Britain's current legislation, clearly designed to ensure that there are no financial incentives to being a refugee. There is a country by country guide to the 35 countries from which Britain receives most asylum applications; the explanation of the conditions that lead to refugee applications makes for harrowing reading.

The International Organisation for Migration (www.iom.int/) attempts to bridge the gap between the refugee and migrant policy: plainly the long term answers to such problems are to end the human rights abuses and wars that lead to forced migration.

Most British doctors will probably be most interested in the issue when they have patients to serve who fall into this category. The Refugee Council of England has an acceptable one page site with an address, phone number, and a little introductory information (www.gn.apc.org/brcslproject/), but if you want more than this, you'll have to write to them.
CIIA Is a Novel Regulator of Detachment-Induced Cell Death
Authors: Kwang Je Kim, Je-Wook Yu, Hyun Sub Hwang, Eui-Ju Choi
Journal: Cancer Research (2010)

Abstract Detachment-induced cell death, or anoikis, is a type of apoptosis that occurs when epithelial cells lose their attachment to the extracellular matrix. Anoikis serves as a physiologic barrier to metastasis. Deviation from the tightly regulated mechanism of detachment-induced cell death might result in progression to metastatic cancer. Here, we investigated the function of CIIA in the regulation of anoikis. CIIA protein was upregulated in colon cancer tissue samples. Knockdown of CIIA in metastatic colorectal carcinoma SW620 and KM12SM cells promoted detachment-induced cell death through the regulation of caspase activation. Knockdown of CIIA also inhibited anchorage-independent growth in soft agar and colony formation after suspension stress. These observations suggest that CIIA is a novel negative regulator of anoikis. Cancer Res; 70(15); 6352–8. ©2010 AACR.
Effect of Potassium on A-V Conduction
Authors: CHARLES FISCH
Journal: Circulation (1970)

"When the potassium is injected slowly, after a time the heart gradually slows to perhaps half its normal rate, the auricle and ventricle being markedly dilated but still contracting synchronously. This is an example of sinus slowing, and is probably due to the direct action of the salt upon what Lewis has termed the `pace-maker' of the heart; it is not due to stimulation of the vagus endings, since it is still produced after administration of atropine. . . . "In other cases an abrupt slowing of the pulse rate occurs, due to dissociation of the auricular and the ventricular rhythms, a condition of 2:1 or of complete heart block being produced. This dissociation is sometimes seen in a heart that is in quite good condition and, upon discontinuing the injection of potassium salts, recovery soon takes place. It cannot be produced with any degree of certainty; since marked sinus slowing, stoppage in diastole, or ventricular fibrillation frequently ensue without this type of heart block being manifested. . . . "In the present state of our knowledge it is legitimate to infer from these results that the block is due to a depression of the conductivity of the auriculoventricular connections from the direct action of the potassium salts upon the musculature. The block is produced in the hearts of animals that have been treated with atropine, so that stimulation of the vagus mechanism is not an essential factor."— Mathison. 1
Musculoskeletal disorders and disability in persons aged 85 and over: a community survey.
Authors: D van Schaardenburg, K J Van den Brande, G J Ligthart, F C Breedveld, J M Hazes
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To study the prevalences of musculoskeletal disorders and disability in the elderly, and the relationship between them. METHODS--A community sample of 73 females and 32 males aged 85 and over underwent a standardised examination at home. Musculoskeletal disorders were classified according to published clinical criteria. The relative effects on disability (a walking distance of &lt; 500 m or dependency in activities of daily living (ADL)) of musculoskeletal disorders and comorbidity were analysed by logistic regression. RESULTS--Musculoskeletal pain was reported by 57% of those interviewed. A major restriction of joint movement range was frequent in the shoulder but uncommon in other joints. A shoulder disorder was found in 27% of subjects, rheumatoid arthritis in 1% and osteoarthritis (OA) of the hand, hip, and knee in five, seven, and 18% of subjects, respectively. Disability was frequent: a walking distance of &lt; 500 m was found in 60% and ADL dependency in 40% of the group. Factors related to one or both of these disability measures included female gender, hip and knee OA, impaired vision, cognitive impairment and neurological disease. CONCLUSION--Musculoskeletal pain and disorders, in addition to disability were frequent in this very elderly population. However, as a cause of disability, other disorders were at least as important as musculoskeletal disorders.
Assisted Suicide: Sheer Cliff or Clinical Reality?-Reply
Authors: Timothy E. Quill
Journal: JAMA (1994)

<h3>In Reply.</h3> —Dr Holt speaks for the many compassionate mainstream physicians who skillfully use palliative care and privately struggle with the agonizing dilemmas still faced sometimes by dying patients and their families. Such physicians often express frustration about the reprimands and abstract, overly simplified solutions espoused by ethicists who seem to ignore the clinical realities that they face.<sup>1</sup>We need to create an open environment that encourages physician compassion and creativity and provides physicians with consultation and support rather than simple proscriptions. The voice of these physicians has been largely missing from the debate about physician-assisted suicide. Dr King reminds us that assisted death should never be a substitution for good palliative care. The criteria proposed by Drs Cassel, Meier, and me attempt to ensure that hospice care has been fully utilized, depression has been treated, and patient judgment is clear and unwavering.<sup>2</sup>Assisted death is not an
Adults With Diabetes Hospitalized With Pandemic Influenza A(H1N1)pdm09—U.S. 2009
Authors: Rahul B. Ganatra, John J. McKenna, Anna M. Bramley, Jacek Skarbinski, Alicia M. Fry, Lyn Finelli, Seema Jain
Journal: Diabetes Care (2013)

In the U.S., diabetes was common among adults hospitalized with pandemic influenza A(H1N1)pdm09 virus (pH1N1) infection, with a prevalence of 15–25% in national case series (1–3). Despite the influenza burden among patients with diabetes, clinical data are limited.

Through two U.S. pH1N1 hospitalizations case series conducted during the spring and fall of 2009 (1,2), medical records of adults ≥18 years old hospitalized with laboratory-confirmed pH1N1 infection were reviewed. Data were collected as part of public health emergency response and deemed not to be research. We compared clinical features between patients with and without diabetes and performed a Mantel-Haenszel analysis, controlling for obesity (BMI ≥30 kg/m2).

Among 319 adults hospitalized with pH1N1 infection, 72 (23%) had diabetes, including 33 of 169 patients (20%) in the spring and 39 of 150 patients (26%) in the fall of 2009. Patients …
cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene
Authors: Javed Khan, Michael L. Bittner, Lao H. Saal, Alicia J. Faller, Ulrike Teichmann, David O. Azorsa, Gerald C. Gooden, William J. Pavan, Jeffrey M. Trent, Paul S. Meltzer
Journal: Nature Genetics (1999)
Reat-time inferior vena caval ultrasonography: normal and abnormal findings and its use in assessing right-heart function.
Authors: G S Mintz, M N Kotler, W R Parry, A S Iskandrian, S A Kane
Journal: Circulation (1981)

We studied the inferior vena cava (IVC) as an index of right-heart function in 111 patients. A two-dimensional echocardiographic sector was used to visualize the IVC, and its M-mode cursor was used to generate a time-motion record of the IVC size and pulsation. Normal subjects had a small presystolic A wave (less than 125% of the end-diastolic IVC dimension), a small systolic V wave (less than 140% of the end-diastolic IVC dimension), and a 50% inspiratory decrease in IVC dimension. The A wave was absent in patients with atrial fibrillation. When normalized for body surface area, mean end-diastolic IVC dimension correlated with mean right atrial pressure (r = 0.72, p less than 0.001). An A wave greater than or equal to 125% of end-diastolic IVC dimension was recorded in 71% of patients with sinus rhythm and an elevated right ventricular end-diastolic pressure of 10 mm Hg or greater, but in no patient with right ventricular end-diastolic pressure of less than 10 mm Hg (p less than 0.001). A V wave greater than or equal to 140% of end-diastolic IVC dimension was recorded in 75% of patients with severe tricuspid insufficiency, but in no patient with mild or no tricuspid insufficiency (p less than 0.001). The inspiratory decrease in IVC dimension correlated with radionuclide right ventricular ejection fraction (r = 0.75, p less than 0.001); no respiratory variation in end-diastolic IVC dimension occurred in patients with significant right ventricular dysfunction (right ventricular ejection less than 25%) or in patients with constrictive pericarditis.
Pleuropulmonary infection with chest wall infiltration by Eikenella corrodens.
Authors: J. W. Killen, G. L. Swift, R. J. White
Journal: Thorax (1996)

Eikenella corrodens is a facultative anaerobic bacillus which is part of the normal flora of the oral cavity and has an unusual antibiotic sensitivity for an anaerobe. The case history is presented of a young man with chest wall infiltration by Eikenella corrodens.
My Name Is Bill: Bill Wilson--His Life and the Creation of Alcoholics Anonymous
Authors: B. I. Liskow
Journal: JAMA (2004)

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
NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS)
Authors: Friederike Schneider, Eva Hoster, Michael Unterhalt, Stephanie Schneider, Annika Dufour, Tobias Benthaus, Gudrun Mellert, Evelin Zellmeier, Stefan K. Bohlander, Michaela Feuring-Buske, Christian Buske, Jan Braess, Susanne Fritsch, Achim Heinecke, Maria C. Sauerland, Wolfgang E. Berdel, Thomas Buechner, Bernhard J. Woermann, Wolfgang Hiddemann, Karsten Spiekermann
Journal: Blood (2009)
Cathepsin D, but not cathepsin E, degrades desmosomes during epidermal desquamation
Authors: S. Igarashi, T. Takizawa, T. Takizawa, Y. Yasuda, H. Uchiwa, S. Hayashi, H. Brysk, J.M. Robinson, K. Yamamoto, M.M. Brysk, T. Horikoshi
Journal: British Journal of Dermatology (2004)

We previously reported that an ambient aspartic proteinase is crucial to desquamation of the stratum corneum at pH 5. Identification of this aspartic proteinase by using enzyme inhibitors suggested it to be cathepsin D, although we could not exclude cathepsin E.To determine the identity of this aspartic proteinase and its distribution within the stratum corneum.We measured enzyme activities of cathepsin D and cathepsin E in the salt and detergent extracts from callus stratum corneum, using a fluorogenic peptide as a substrate and comparing the effect of addition of Ascaris pepsin inhibitor (specific for cathepsin E) with that of pepstatin A (which inhibits both cathepsin D and cathepsin E). Both enzymes were then extracted and purified from plantar stratum corneum samples and identified by Western blotting. Immunofluorescence microscopy was used to investigate the localization of proteinases within human plantar stratum corneum sample sections.We found that 20% of total aspartic proteinase activity could be attributed to cathepsin E, the remainder to cathepsin D. Two subunits of cathepsin D were identified, a mature active form at 33 kDa and an intermediate active form at 48 kDa; cathepsin E was also identified at 48 kDa, although in a stained band 10-fold weaker in the immunoblot. Immunofluorescence microscopy showed the antibody to cathepsin D to be localized in the lipid envelopes of the stratum corneum, whereas that to cathepsin E stained the tissue diffusely. The labelling for cathepsin D was similar to that observed for desmosomes, and immunoelectron microscopy confirmed that cathepsin D was present on desmosomes. On the other hand, cathepsin E occurred intracellularly within the squames.We conclude that cathepsin D, and not cathepsin E, causes desquamation by degrading desmosomes.
A New Diagnostic Test for Pulmonary Embolism: How Good and How Costly?
Authors: S. James Adelstein, Barbara J. McNeil
Journal: New England Journal of Medicine (1978)

Pulmonary embolism is said to be an underdiagnosed disease, an overdiagnosed disease, a life-threatening entity and a masquerader. Little wonder that there is intense interest in developing technics to diagnose it more accurately. Dalen and Alpert estimate that there are over 600,000 new cases of pulmonary embolism in the United States annually.1 Three quarters of these cases lack a correct diagnosis, and among these patients, the mortality is 30 per cent. Of those in whom the diagnosis is made and treatment instituted, the mortality rate is estimated as 8 per cent. Although these mortality figures are skewed by a preponderance . . .
College repays a favor to medicine—two centuries later
Authors: Phil Gunby
Journal: JAMA (1984)

Medicine apparently did Dickinson College a favor more than 200 years ago. Now, Dickinson's president in a sense may be able to repay that favor through an unofficial "National Advisory Council on Premedical Education" that the college will support initially. The council will first meet on the campus in October. Samuel A. Banks, PhD, Dickinson's president since 1975, will chair the nine-member panel. Dickinson, which is located in Carlisle in southeastern Pennsylvania, has an enrollment of about 1,800 students. Medicine figures favorably in its history because Benjamin Rush, MD, prominent in the patriotic cause during the American Revolution, is said to have "persuaded the Presbyterians to found Dickinson [College]" and to have served as a trustee (<i>Dictionary of American Biography</i>, New York, Charles Scribner's Sons, 1965, pp 227-234). (Scholars have noted that "although five signers of the Declaration [of Independence] are known to have practiced medicine, Rush was the only
ANTIBIOTIC AND CHEMOTHERAPEUTIC AGENTS IN INFECTIONS OF THE BLOOD STREAM AND HEART
Authors: Wallace E. Herrell
Journal: JAMA (1952)

Recent developments in therapy for infections of the blood stream and heart have proved the value of the sulfonamides and the antibiotics. But it must be realized that their use also serves to complicate the condition in some cases.  BACTEREMIA  Before the introduction of sulfonamide compounds, patients with either staphylococcic or streptococcic bacteremia, who were 50 years of age or older, had only 1 chance in 10 to recover. Intensive use of the sulfonamides raised the rate of recovery from bacteremia to as high as 50 or 60%. Of those types of bacteremia caused by gram-positive micro-organisms, probably the two most commonly encountered are those caused by Micrococcus pyogenes and Streptococcus pyogenes. The etiological organism next in order of frequency is Diplococcus pneumoniae, followed by the indifferent strains and anaerobic strains of streptococci. Bacteremia caused by gram-negative organisms is also encountered fairly frequently. The commonest infection of this type is
AB0562 A double-blind, placebo-controlled, multicenter trial of tocilizumab in moderate to severe active RA patients with inadequate response to methotrexate in korean population:
Authors: M.J. Lim, S.H. Park, S.-C. Shim, H.J. Baek, D.-H. Yoo, H.A. Kim, S.K. Lee, Y.J. Lee, Y.E. Park, H.-S. Cha, W. Park, Y.-W. Song
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Interleukin-6 (IL-6), a proinflammatory cytokine, is thought to play a major pathological role in rheumatoid arthritis (RA). Tocilizumab is humanized anti IL-6 receptor monoclonal antibody which has been shown to improve signs and symptoms of RA. <h3>Objectives</h3> To investigate the efficacy and safety of tocilizumab in a Korean population. <h3>Methods</h3> This clinical trial was a 24-week phase III, randomized, double-blind, placebo-controlled, multicenter trial with two treatments arms and conducted from October, 2009 to October, 2010. The eligible patients had moderate to severe active RA, inadequately responding to MTX (or DMARDs). Tocilizumab at a dose of 8mg/kg or placebo were administered in a blinded manner, intravenously every 4 weeks, with stable dose of methotrexate (MTX) or other DMARDs. <h3>Results</h3> Total of 80 patients completed 24 week’s treatment with 40 patients in each treatment arm. At week 24, proportions of ACR 20, ACR 50, DAS28 remission and EULAR response were significantly higher in Tocilizumab group than in placebo group (<i>p</i> &lt;0.0001, <i>p</i>=0.0002, <i>p</i>=0.0002 and <i>p</i>&lt;0.0001, respectively as shown in Table 1). The mean hemoglobin level was increased and the rheumatoid factor titer was decreased in Tocilizumab group, compared to those of placebo group (<i>p</i>=0.0002, <i>p</i>=0.0055, respectively). Adverse drug reactions were more frequent in Tocilizumab group than in placebo group as follows; increased SGPT (21%), granulocytopenia (17%), leukocytopenia (15%), hypercholesterolemia (13%), pharyngitis (13%), and increased SGOT (10%). There were more incidences of serious adverse drug reactions in Tocilizumab group than in placebo group, but it was not significant (<i>p</i>=0.0548). <h3>Conclusions</h3> In Korean population, administration of tocilizumab 8 mg/kg in combination with MTX (with or without other DMARDs) reduced RA activity significantly. Most of RA activity parameters including ACR 20, ACR 50, DAS 28 remission and EULAR response were achieved more frequently in Tocilizumab group than in placebo group. Tocilizumab was generally well tolerated since no safety issue was observed during the study. This study was financially supported by JW Pharmaceutical Co. (KFDA clinical trial-146). <h3>References</h3> Maini RN, et al. Arthritis Rheum. 2006;54(9):2817-29. Jones G, et al. Ann Rheum Dis. 2010;69(1):88-96. <h3>Disclosure of Interest</h3> None Declared