tbuckley/cabot-search huggingface dataset:
Coexistent Felty's syndrome and palindromic rheumatism.
Authors: R E Alvillar, L O'Grady, D Robbins
Journal: Annals of the Rheumatic Diseases (1991)

Palindromic rheumatism is a syndrome of intermittent abrupt onset monoarthritis with asymptomatic intercritical periods of variable duration, which commonly evolves into rheumatoid arthritis. Felty's syndrome consists of leucopenia (selective neutropenia) and splenomegaly, usually occurring in longstanding classic rheumatoid arthritis. Felty's syndrome can be confused with the more recently recognised rheumatoid arthritis associated large granular lymphocyte proliferative disease. This paper describes a patient with palindromic rheumatism presenting with Felty's syndrome in whom large granular lymphocyte proliferative disease was ruled out by lymphocyte phenotyping.
Diet and Diabetes
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2004)

This is the second of a series of articles on presentations at the American Diabetes Association Annual Meeting, Orlando, Florida, 4–8 June 2004, addressing issues related to diet and current approaches of surgical treatment of obesity.

John Miles (Rochester, MN) discussed effects of meal ingestion on protein metabolism, acute effects of dietary protein and amino acids on glucose metabolism, and effects of protein in persons with diabetes, noting that insulin decreases endogenous proteolysis during a mixed meal. In a study of protein ingestion in persons with diabetes, plasma amino acids and, subsequently, urea levels increased. Usually, increasing protein ingestion is associated with protein oxidation, which is important as there is no physiologic mechanism for accumulation of protein stores, while conversely we adapt to decreasing dietary protein by decreasing amino acid oxidation. The effect of protein on glucose metabolism can be studied by measurement of arterial-venous balance, with evidence that amino acids displace glucose as metabolic fuels. Assessing independent effects of protein and of insulin on systemic and regional glucose metabolism, Miles showed evidence that insulin decreases circulating amino acid levels, and that with addition of amino acid infusion, there is decreased insulin-mediated glucose uptake and decreased insulin-mediated suppression of hepatic glucose output. Thus, amino acids cause a form of insulin resistance. Following acute protein ingestion in normal persons, however, there is little change in glucose homeostasis, presumably reflecting increases in insulin and in glucagon levels. As far as chronic effects of isocaloric high- or low-protein diets administered for 5 weeks in persons with diabetes, there is evidence of a decrease in glucose and triglyceride levels with a high-protein diet, as well as a trend to weight loss. The energy cost of fat ingestion and storage is low, and that for carbohydrate is modest, but there is a 25–30% thermic effect …
Value of examining buffy coats for intragranulocytic micro-organisms in patients with fever.
Authors: J P Studer, M P Glauser, M Schapira
Journal: BMJ (1979)

To determine the significance of the presence of intragranulocytic micro-organisms in the blood buffy coat in patients with suspected infection, buffy coat examination and blood cultures were simultaneously performed in 455 consecutive patients with fever. There was no general correlation between the finding of intragranulocytic micro-organisms in the buffy coat and positive blood cultures. Patients with persistent bacteraemia and sterile blood cultures were, however, shown to have persistently positive buffy coat findings on repeated examination. These patients, who had culture-negative endocarditis or catheter-associated infections, had sterile blood cultures because of antibiotic treatment. Repeated positive findings in the buffy coat may therefore be valuable in detecting patients with persistent bacteraemia, but sporadic findings of micro-organisms in the buffy coats of acutely ill patients seem to have little diagnostic value.
Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study.
Authors: J L Jenner, J M Ordovas, S Lamon-Fava, M M Schaefer, P W Wilson, W P Castelli, E J Schaefer
Journal: Circulation (1993)

BACKGROUND Lipoprotein(a) [Lp(a)] is an atherogenic particle that structurally resembles a low density lipoprotein (LDL) particle but contains a molecule of apolipoprotein(a) attached to apolipoprotein B-100 by a disulfide bond. Because elevated plasma levels of Lp(a) have been shown to be an independent risk factor for coronary artery disease, it is important to define normal ranges for this lipoprotein. METHODS AND RESULTS We have measured Lp(a) in 1,284 men (mean age, 48 +/- 10 years) and 1,394 women (mean age, 48 +/- 10 years) free of cardiovascular and cerebrovascular disease and not on medications known to affect lipids who were seen at the third examination cycle of the Framingham Offspring Study. Plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay, which uses a "capture" monoclonal anti-apo(a) antibody that does not cross-react with plasminogen, and a polyclonal anti-apo(a) antibody conjugated to horseradish peroxidase. The assay was calibrated to total Lp(a) mass. The Lp(a) frequency distribution was highly skewed to the right, with 56% of the values in the 0-10-mg/dL range. Mean plasma Lp(a) concentrations were 14 +/- 17 mg/dL in men and 15 +/- 17 mg/dL in women. Values of more than 38 mg/dL were above the 90th percentile and values of more than 22 mg/dL were above the 75th percentile in both men and women. CONCLUSIONS We have determined mean Lp(a) levels for men and women participating in the Framingham Offspring Study. In this population, there was an inverse association between plasma levels of Lp(a) and triglycerides for both sexes (p &lt; 0.006), but triglycerides accounted for only approximately 0.5% of the variation in Lp(a) levels. Associations of Lp(a) levels with total and LDL cholesterol levels were not significant after correction for the estimated contribution of Lp(a) cholesterol to total and LDL cholesterol. After controlling for age, Lp(a) values were 8% greater in postmenopausal women than in premenopausal women, but this difference was not statistically significant. Body mass index, alcohol consumption, cigarette smoking, use of beta-blockers or cholesterol-lowering medications, and use of drugs for the treatment of diabetes and hypertension were not correlated with Lp(a) levels.
<i>Clostridium difficile</i>binary toxin CDT
Authors: Dale N Gerding, Stuart Johnson, Maja Rupnik, Klaus Aktories
Journal: Gut Microbes (2013)

Binary toxin (CDT) is frequently observed in Clostridium difficile strains associated with increased severity of C. difficile infection (CDI). CDT belongs to the family of binary ADP-ribosylating toxins consisting of two separate toxin components: CDTa, the enzymatic ADP-ribosyltransferase which modifies actin, and CDTb which binds to host cells and translocates CDTa into the cytosol. CDTb is activated by serine proteases and binds to lipolysis stimulated lipoprotein receptor. ADP-ribosylation induces depolymerization of the actin cytoskeleton. Toxin-induced actin depolymerization also produces microtubule-based membrane protrusions which form a network on epithelial cells and increase bacterial adherence. Multiple clinical studies indicate an association between binary toxin genes in C. difficile and increased 30-d CDI mortality independent of PCR ribotype. Further studies including measures of binary toxin in stool, analyses of CDI mortality caused by CDT-producing strains, and examination of the relationship of CDT expression to TcdA and TcdB toxin variants and PCR ribotypes are needed.
Did Health Care Injustice Fuel Rage, Riots?
Authors: Stuart M. Copperman
Journal: JAMA (1992)

To the Editor.  —The article by Paul Cotton 1 was biased and inflammatory and did little to promote understanding of either our current health care access problem or racial unrest. Cotton uses terms like abysmal to describe health care access, and political constipation that allows this crisis to persist. He implies that physicians, like the caring physician whose records were burned during Los Angeles' wanton disorder and destruction, merely say (MediCal's) meager payments do not meet even their overhead costs on a quoted $12 to $16 per visit. You're darn right they do not meet their overhead costs! And no one can lose money on every patient and make it up in volume. That's elementary economics.  I must remind Cotton that it was not the dedicated physicians who burned whole blocks of businesses destroying 30 000 jobs and concomitant health insurance for many workers and their families. It is inflammatory
Prognostic Value of Myocardial Contrast Delayed Enhancement With 64-Slice Multidetector Computed Tomography After Acute Myocardial Infarction
Authors: Akira Sato, Toshihiro Nozato, Hiroyuki Hikita, Daiki Akiyama, Hidetaka Nishina, Tomoya Hoshi, Hideaki Aihara, Yuki Kakefuda, Hiroaki Watabe, Michiaki Hiroe, Kazutaka Aonuma
Journal: Journal of the American College of Cardiology (2012)
Surgeon jailed for infecting patients
Authors: C Dyer
Journal: BMJ (1994)

A surgeon infected with hepatitis B virus who lied about his condition and knowingly put hundreds of patients at risk was jailed for a year last week, in a case that made legal history. Umesh Gaud, aged 41, of Bethnal Green, east London, pleaded guilty at Southwark Crown Court in London to the common law charge of causing a public nuisance. The closest precedent is thought to be the prosecution of a woman for wheeling her baby, infected with smallpox, through the streets in 1815.

Dr Gaud, who was educated in Calcutta, falsified his curriculum vitae to secure jobs at the Royal London and London Chest Hospitals and submitted patients' blood instead of his own when …
Formation and Antitumor Activity of PNU-159682, A Major Metabolite of Nemorubicin in Human Liver Microsomes
Authors: Luigi Quintieri, Cristina Geroni, Marianna Fantin, Rosangela Battaglia, Antonio Rosato, William Speed, Paola Zanovello, Maura Floreani
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Nemorubicin (3′-deamino-3′-[2″(S)-methoxy-4″-morpholinyl]doxorubicin; MMDX) is an investigational drug currently in phase II/III clinical testing in hepatocellular carcinoma. A bioactivation product of MMDX, 3′-deamino-3″,4′-anhydro-[2″(S)-methoxy-3″(R)-oxy-4″-morpholinyl]doxorubicin (PNU-159682), has been recently identified in an incubate of the drug with NADPH-supplemented rat liver microsomes. The aims of this study were to obtain information about MMDX biotransformation to PNU-159682 in humans, and to explore the antitumor activity of PNU-159682. Experimental Design: Human liver microsomes (HLM) and microsomes from genetically engineered cell lines expressing individual human cytochrome P450s (CYP) were used to study MMDX biotransformation. We also examined the cytotoxicity and antitumor activity of PNU-159682 using a panel of in vitro-cultured human tumor cell lines and tumor-bearing mice, respectively. Results: HLMs converted MMDX to a major metabolite, whose retention time in liquid chromatography and ion fragmentation in tandem mass spectrometry were identical to those of synthetic PNU-159682. In a bank of HLMs from 10 donors, rates of PNU-159682 formation correlated significantly with three distinct CYP3A-mediated activities. Troleandomycin and ketoconazole, both inhibitors of CYP3A, markedly reduced PNU-159682 formation by HLMs; the reaction was also concentration-dependently inhibited by a monoclonal antibody to CYP3A4/5. Of the 10 cDNA-expressed CYPs examined, only CYP3A4 formed PNU-159682. In addition, PNU-159682 was remarkably more cytotoxic than MMDX and doxorubicin in vitro, and was effective in the two in vivo tumor models tested, i.e., disseminated murine L1210 leukemia and MX-1 human mammary carcinoma xenografts. Conclusions: CYP3A4, the major CYP in human liver, converts MMDX to a more cytotoxic metabolite, PNU-159682, which retains antitumor activity in vivo.
O58 RESULTS FROM THE PHASE 2 PEARL-I STUDY: INTERFERON-FREE REGIMENS OF ABT-450/R + ABT-267 WITH OR WITHOUT RIBAVIRIN IN PATIENTS WITH HCV GENOTYPE 4 INFECTION
Authors: C. Hezode, P. Marcellin, S. Pol, T. Hassanein, K. Fleischer-Stepniewska, T. Baykal, T. Wang, S.S. Lovell, T. Pilot-Matias, R.A. Vilchez
Journal: Journal of Hepatology (2014)
Exercise Capacity in Hypertrophic Cardiomyopathy
Authors: Suhas S. Lele, Helen L. Thomson, Hiromi Seo, Israel Belenkie, William J. McKenna, Michael P. Frenneaux
Journal: Circulation (1995)

Background We previously showed that exercise capacity in patients with hypertrophic cardiomyopathy (HCM) is related to peak exercise cardiac output. Cardiac output augmentation during exercise is normally dependent on heart rate (HR) response and stroke volume (SV) augmentation by increased left ventricular end-diastolic volume and/or increased contractility. We hypothesized that in contrast to normal subjects, peak exercise capacity in patients with HCM is determined by the diastolic filling characteristics of the left ventricle during exercise, which would in turn determine the degree to which SV is augmented, and that HR is a relatively unimportant determinant of peak exercise capacity. Methods and Results Twenty-three patients with HCM underwent invasive hemodynamic evaluation and measurement of maximal oxygen consumption (V̇ o 2max ) during erect treadmill exercise to assess the relative importance of changes in HR and SV in determining exercise capacity. Hemodynamic responses to erect and supine exercise were compared in 10 of these patients. In a separate group of 46 patients with HCM, the relation between V̇ o 2max and exercise diastolic filling indexes was assessed. Peak HR during erect exercise was 92±8% of predicted maximum. V̇ o 2max was 29.0±6.4 mL · kg −1 · min −1 and was related significantly to peak exercise cardiac index and SV index ( r =.71, P &lt;.0001 and r =.66, P =.001, respectively) but not to peak HR, HR deficit, or resting or peak pulmonary capillary wedge pressure. Peak cardiac output during erect exercise was not related to peak HR ( r =.13, P =NS). When erect and supine exercise were compared, peak HR was lower in the supine position (153.3±19.9 beats per minute supine versus 172.0±17.6 beats per minute erect, P =.003), but peak exercise cardiac index was similar (7.9±2.6 L · min −1 · m −2 supine versus 7.5±2.8 L · min −1 · m −2 erect). Pulmonary capillary wedge pressure was higher at rest in the supine versus erect position (15.3±5.2 versus 8.1±6.1 mm Hg) but was not significantly higher at peak exercise in the supine versus erect position (28.5±8 versus 22.4±11.6 mm Hg erect, P =NS). In the separate group of 46 patients with HCM, V̇ o 2max was significantly inversely related to time to peak filling at peak exercise ( r =−.60, P &lt;.0001) but did not correlate with time to peak filling at rest, resting ejection fraction, peak filling rate, or peak exercise peak filling rate. Conclusions SV is the major determinant of peak exercise capacity in the erect position in patients with hypertrophic cardiomyopathy. This in turn is determined by the exercise left ventricular diastolic filling characteristics. HR augmentation does not appear to be a major determinant of peak cardiac output in the erect position.
On the Symmetry of the Pancreas and Spleen
Authors: D. Embleton
Journal: BMJ (1873)

IN a paper read at the Newcastle meeting of the British Medical Asso- ciation, in August, and printed in the JOURNAI in October and November, I870, I endeavonired to explain the mode in which, as it occur- red to me, the above-named pains arise in diseases of the liver, and to enumerate the diseases of that organ in which the pains occur.In the present paper I wish to fulfil a promise made in the former, that I would endeavour to show that similar pains occur at the shoulder-tip, and in other parts, in diseases of other organs of the pneumogastric set ies.Under this term I comprise, of course, all those viscera that receive a supply of nerves from the medulla oblongata through the par vagum.They all lie in the neck, chest, and abdomen; and it is only sith regard to some of those in the latter cavity that any doubt exists as to their really belonging to the series, for anatomists differ as to the distribution of the abdominal branclhes of the par vagum.The majority agree that the stomach, liver, spleen, and pancreas, receive pneumogastric nerves, although the lhepatic and splenic branches are variously described by different authors; some exclude from the series the pancreas, the kid- neys, and suprarenal bodies; whilst otlhers include in it not only these organs, but a considerable, though unascertained extent, of the small and large intestines.To fix the exact inferior limits of the wandering pair is a matter of great difficulty, perhaps of impossibility, on account of the complexity of the abdominal nervous system, throuah the intricate interlacement of the branches of the par vagum with those of the sympathetic system.There is good evidence, from our latest anatomists, that the pancreas receives nerves from the par vagum, and that the kidneys and supra- renial bodies, and a considerable extent of the alimentary canal below the stomach, also receive branches from the same source.All the vis- cera receive, together with their pneumogastric branches, a copious supply of plexuses of nerves and ganglia from the sympathetic system, and a few small tsw igs from the spinal cord.
Endoscopy to endocytoscopy to endopathology: Are we ready?
Authors: A. Chak
Journal: Endoscopy (2007)

The 21st century has ushered in an astonishing, even dizzying, number of new endoscopic imaging modalities - high magnification endoscopy, high definition endoscopy, autofluorescence endoscopy, endoscopic optical coherence tomography, narrow band imaging, confocal endoscopy, and now endocytoscopy. In the United States and Western Europe, Barrett’s esophagus has become the ”model disease” for the application of these developing technologies.
Surgeons' Hall — The Story of the First Medical-School Building in the United States
Authors: Lawrence C. Parish, Thomas N. Haviland
Journal: New England Journal of Medicine (1965)

THE following notice appeared in Franklin's Pennsylvania Gazette 1:Dr. Shippen's course of anatomical lectures will begin on Thursday, the 14th of November, 1765; it will consist of about sixty lectures, in which the situation, figure, and structure of all parts of the human body will be demonstrated on the fresh subject....Two months before, William Shippen, Jr. (1736–1808), recently returned from Edinburgh and the Monros' tutelage, petitioned the trustees of the College of Philadelphia, setting forth his qualifications and requesting a position in the newly organized medical faculty. That august body unanimously elected him to the professorship of anatomy . . .
Abstract 5558: Interplay between BRAF, p16, p53, and MIB1 in pediatric low grade gliomas
Authors: Craig Horbinski, Marina N. Nikiforova, Jill Hagenkord, Ronald L. Hamilton, Ian F. Pollack
Journal: Cancer Research (2012)

Abstract BRAF rearrangements and BRAF V600E point mutations are recurring events in pediatric low-grade gliomas. However, their clinical significance, including possible interactions between these markers and other glioma biomarkers, is unclear. In this study a retrospective cohort of 198 pediatric low-grade gliomas (including 40 treated with adjuvant therapy) was analyzed for BRAF rearrangements, BRAF V600E, p16/CDKN2A deletion, p53 expression, and MIB1 proliferation index. In tumors with BRAF rearrangement, homozygous p16 deletion correlated with shorter PFS (P = 0.04). High MIB1 proliferation index strongly trended toward correlating with worse response to adjuvant therapy (P = 0.06). On multivariate analyses, the two most consistently powerful independent adverse prognostic markers were midline location (P = 0.0001) and p16 deletion (P = 0.03). Tumors with BRAF V600E had a strong trend toward an increased risk for progression (hazard ratio = 2.48, P = 0.07), whereas those with BRAF rearrangement had a milder trend toward reduced risk (hazard ratio = 0.54, P = 0.15). These data suggest that p16 deletion adversely impacts the outcomes of BRAF-driven gliomas; that high proliferation index may be a better marker of progression risk than BRAF; that BRAF rearrangement and BRAF V600E might not necessarily produce comparable outcomes; and that none of these markers is stronger than tumor location in determining prognosis in pediatric low-grade gliomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5558. doi:1538-7445.AM2012-5558
Little evidence that primary care providers stop child and teen drug use, US task force says
Authors: M. McCarthy
Journal: BMJ (2014)

There is little evidence that interventions by primary care providers can prevent or reduce drug use in children and adolescents under age 18, a systematic review by the US Preventive Services Task Force has found.1

It has been estimated that 1 in 10 adolescents uses illicit, prescription, or over-the-counter drugs for non-medical purposes—misuse that …
The double-RNA-specific adenosine deaminase (DSRAD) gene in dyschromatosis symmetrica hereditaria patients: two novel mutations and one previously described
Authors: X-K. Sun, A-E. Xu, J-F. Chen, X. Tang
Journal: British Journal of Dermatology (2005)

Dyschromatosis symmetrica hereditaria (DSH, MIM 127400) is an autosomal dominant pigmentary genodermatosis. Pathogenic mutations in the double-RNA-specific adenosine deaminase (DSRAD) gene encoding an RNA editing enzyme have recently been identified.To identify gene mutations of DSRAD in Chinese patients with DSH.Three unrelated Chinese patients with DSH were subjected to mutation detection in DSRAD. Two had family histories of DSH. All the coding exons and their flanking sequences were amplified and sequenced.All three patients had heterozygous mutations including one non-sense, one frameshift and one missense mutation in DSRAD.Two novel mutations, c.3169delC (p.L1057fs) and c.3247C-->T (p.R1083C), and one recurrent mutation c.1420C-->T (p.R474X), were found in this series of Chinese patients with DSH.