tbuckley/cabot-search huggingface dataset:
PTH-041 Polyp Cancers: When is Surgical Resection Needed ?
Authors: R Rameshshanker, A King, S Catnach, S Cerys, B Macfarlane
Journal: Gut (2013)

<h3>Introduction</h3> The Bowel Cancer Screening Program (BCSP) has been successful in detecting early stage bowel cancer, including polyp cancers. Most polyp cancers are not recognised as such at the index colonoscopy and are managed initially with endoscopic resection. There are histological criteria to predict high risk polyp cancers and need for further surgical resection. The decision is not always clear cut, and who to refer for surgery is difficult. A single centre experience is reported <h3>Methods</h3> Polyp cancers detected through the BCSP at West Herts NHS Trust between August 2008 and December 2011 were identified. Endoscopy reports, polyp histology, surgical referrals and surgical histology were analysed. <h3>Results</h3> 1334 colonoscopies were performed and 25 polyp cancers which had been managed initially with endoscopic resection were identified. Twenty four were within recto-sigmoid area, size range 1–4 cm. No polyp cancers were poorly differentiated. Patient age range was 60–74 yrs, median 66 yrs. Fourteen patients had endoscopic resection (ER) alone: thirteen remain disease free at 1 year endoscopic follow up, one patient did not attend. Of the pedunculated polyp cancers, two were Haggitt 1 (H1), four Haggitt 2 (H<sub>2</sub>) and three Haggitt 3 (H3). The resection margin (RM) ranged from 1.5 to 12 mm. There was tumour budding in just one, but the RM was 12 mm. No case had lympho vascular invasion (LVI). Of the sessile polyp cancers there were two Kikuchi 1 (K1), two Kikuchi 2 (K2) and one Kikuchi 3(K3). There was budding in one case, a K1 polyp, and one LVI in a K2 polyp but with 4 mm RM. The K3 polyp had budding, no LVI and RM 0.5-MRI and CT scans were negative in this patient. Eleven patients were referred for surgery post ER. Nine patients had no residual tumour. In these nine patients, polyp features dictating referral were: one H<sub>2</sub> with budding and 0.5 mm RM, one H3 with LVI and 1 mm RM, one H3 with budding and 1 mm RM, one H3 with 0.5 mm RM, one H3 RM not clear, one H3 with 2mm RM no LVI or budding, one K2 with budding LVI and 0.5 mm RM, two K3 RM not clear. Two patients had cancer: one pT1pN1Mx (polyp cancer: H3 no budding or LVI RM 1mm) and pT1pN0Mx (polyp cancer: K2 with budding RM 0.5) <h3>Conclusion</h3> When all three high risk histological features (budding, LVI, RM &lt; 1mm) are absent or present a decision re surgical referral can be straightforward. Using these parameters, in our study, probably one patient more should have been referred for surgical resection, and one patient less. The decision challenge lies when just one or two parameters are present. A pessimistic view is that 82% of our patients had unnecessary surgery, an optimistic one that 18% had appropriate surgery. Age and associated morbidity are also important factors illustrating the value of the MDT in these challenging decisions <h3>Disclosure of Interest</h3> None Declared.
Abstract 5517: Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-α signal transduction in CD4+ T cells from patients with gastrointestinal malignancy
Authors: Bethany L. Mundy, Gregory S. Young, Todd Bauer, Elaine Binkley, Mark Bloomston, Matthew A. Bill, Tanios Bekaii-Saab, William E. Carson, Gregory B. Lesinski
Journal: Cancer Research (2011)

Abstract Interferon-alpha (IFNα) can promote anti-tumor immunity through its actions on immune cells. We have shown in murine models that a class of immune suppressor cells known as myeloid-derived suppressor cells (MDSC) have inhibitory effects on IFN signal transduction and gene regulation. Interleukin (IL)-6 and IL-10 are produced by tumor cells in cancer patients and can regulate the survival and function of MDSC. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets and IFNα-induced signal transduction in 40 patients with gastrointestinal (GI) malignancies. Plasma IL-6 and IL-10 levels were significantly higher in patients versus normal donors. CD33+HLADR−CD11b+CD15+ and CD33+HLADR−/lowCD14+ MDSC were also elevated in patients versus normal donors (p&amp;lt;0.0001). Prior studies suggest that CD15 divides human MDSC into granulocytic (CD15+) and monocytic (CD15−) subsets. Therefore relationships between CD15 expression on MDSC and cytokines elevated in GI patients were examined. A significant correlation between plasma IL-6 with CD33+HLADRCD15+ MDSC (p=0.008) and IL10 with CD33+HLADR−CD15− MDSC (p=0.002) was observed. The level of CD15+ and CD15− but not CD14+ MDSC subsets were inversely correlated with IFNα-induced STAT1 phosphorylation in CD4+ T cells, while co-culture with in vitro generated MDSC led to reduced IFNα-responsiveness in PBMC from normal donors. In a multivariable Cox proportional hazards model, an increased percentage of the CD33+HLADR−CD15− MDSC subset was associated with reduced overall survival (hazard ratio = 1.43; p = 0.049) while an increased percentage of the CD33+HLADR−/lowCD14+ subset was associated with greater overall survival (hazard ratio = 0.69, p=0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets and IFNα responsiveness in patients with GI malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5517. doi:10.1158/1538-7445.AM2011-5517
Cachectin/tumor necrosis factor-alpha formation in human decidua. Potential role of cytokines in infection-induced preterm labor.
Authors: M L Casey, S M Cox, B Beutler, L Milewich, P C MacDonald
Journal: Journal of Clinical Investigation (1989)

This study was conducted as part of an investigation to evaluate the hypothesis that bacterial toxins (LPS or lipoteichoic acid), acting on macrophage-like uterine decidua to cause increased formation of cytokines, may be involved in the pathogenesis of infection-associated preterm labor. We found that cachectin/tumor necrosis factor-alpha (TNF-alpha) was synthesized and secreted into the culture medium by human decidual cells and explants in response to treatment with LPS. LPS treatment also caused an increase in PGF2 alpha production by decidual cells and explants. In amnion cells in monolayer culture, TNF-alpha stimulated PGE2 formation, and TNF-alpha was cytostatic (inhibited [3H]thymidine incorporation into DNA) but not cytolytic in amnion cells. TNF-alpha was not detectable (less than 0.34 ng/ml) in the amniotic fluid of normal pregnancies at midtrimester or at term before or after the onset of labor (n = 44); but TNF-alpha was present at concentrations between 2.8 and 22.3 ng/ml in amniotic fluids of 4 of 20 pregnancies with intact membranes complicated by preterm labor (less than 34 wk gestational age). LPS was present in 10 of the 20 amniotic fluids of preterm labor pregnancies, including all four in which TNF-alpha was present. Bacteria were identified in only one of the four LPS-positive, TNF-alpha-positive fluids. Cytokine formation in macrophage-like decidua may serve a fundamental role in the pathogenesis of preterm labor, including increased prostaglandin formation and premature rupture of the membranes.
Tracking Drug Quality
Authors: M. J. Friedrich
Journal: JAMA (2011)

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
I certified deaths after judicial executions--and I believe capital punishment should be abolished
Authors: A. E. Joseph
Journal: BMJ (2014)

Working in forensic medicine in Sri Lanka included gruesome duties for Anton E Joseph 

Many people have raised justifiable concerns about the use of inappropriate drugs to try to achieve a humane way of carrying out capital punishment, as well as about botched executions.1 2 3 Society seems undecided about the legal justification to take away human life as a punishment. My opinion is that death sentences are legalised murder. I would rather not enter into this controversy, but I do wish to share my unusual professional experience of capital punishment.

When I was employed as a lecturer in forensic medicine in Sri Lanka in the 1960s, my duties included being present at executions by hanging, declaring death before the body was taken down, and performing an autopsy (don’t ask me why)—which I limited to a dissection of the neck to assess damage to the spinal cord and vertebrae. The bodies were not released to relatives but were given state burials in unmarked graves.

At the four executions I witnessed, three …
Major Depression, Antidepressant Medication and the Risk of Obesity
Authors: Scott B. Patten, Jeanne V.A. Williams, Dina H. Lavorato, Lauren Brown, Lindsay McLaren, Michael Eliasziw
Journal: Psychotherapy and Psychosomatics (2009)

Cross-sectional studies have reported an association between major depressive episode (MDE) and obesity. The objective of this longitudinal analysis was to determine whether MDE increase the risk of becoming obese over a 10-year period.We used data from the Canadian National Population Health Survey (NPHS), a longitudinal study of a representative cohort of household residents in Canada. The incidence of obesity, defined as a body mass index (BMI) of > or =30, was evaluated in respondents who were 18 years or older at the time of a baseline interview in 1994. MDE was assessed using a brief diagnostic instrument.The risk of obesity was not elevated in association with MDE, either in unadjusted or covariate-adjusted analyses. The strongest predictor of obesity was a BMI in the overweight (but not obese) range. Effects were also seen for (younger) age, (female) sex, a sedentary activity pattern, low income and exposure to antidepressant medications. Unexpectedly, significant effects were seen for serotonin-reuptake-inhibiting antidepressants and venlafaxine, but neither for tricyclic antidepressants nor antipsychotic medications.MDE does not appear to increase the risk of obesity. The cross-sectional associations that have been reported, albeit inconsistently, in the literature probably represent an effect of obesity on MDE risk. Pharmacologic treatment with antidepressants may be associated with an increased risk of obesity, and strategies to offset this risk may be useful in clinical practice.
Erythrocyte deformation in duchenne muscular dystrophy.
Authors: E M Lumb, A E Emery
Journal: BMJ (1975)

The Detector Circuit Description.-Twotransistors are used in a Darlington connection to provide a high gain.When the resistance between the input terminals Ti and T2 (see fig.) is lowered the transistor collector currents increase and one coil of the remanent relay RL is energized and opens both sets of contacts.The relay remains in this state even if the coil current returns to zero.The contacts RL2 are connected in series with the battery supply to an electric clock and contacts RL1 are connected in series with the internal batteries.The unit, therefore, consumes no current except during the very short time that the relay contacts are actually changing over.When the resistance at the input terminals is raised again the contacts of the remanent relay may be closed by pressing the reset button, which switches the relay back to its resting state.Operating Instructions.-Thesensing pad is connected to push-type terminals on one side of the unit and the clock battery supply is broken through a two-pin plug.If the pad is dry the input terminal resistance is high and the clock will start when the reset button is pressed.The sensitivity control VRI sets the terminal resistance at which the unit operates.
Increased ultrasonic myocardial reflectivity in patients with thalassemia major and iron overload
Authors: Paolo Bellotti, Fabio Lattanzi, Eugenio Picano, Francesco Chiarella, Alessandro Mazzarisi, Cristina Melevendi, Gianluca Forni, Luigi Landini, Carlo Vecchio
Journal: Journal of the American College of Cardiology (1991)
Hematopoietic Cell-Specific Deletion of Toll-like Receptor 4 Ameliorates Hepatic and Adipose Tissue Insulin Resistance in High-Fat-Fed Mice
Authors: Maziyar Saberi, Niels-Bjarne Woods, Carl de Luca, Simon Schenk, Juu Chin Lu, Gautam Bandyopadhyay, Inder M. Verma, Jerrold M. Olefsky
Journal: Cell Metabolism (2009)
ETIOLOGY OF CHRONIC NEPHRITIS.
Authors: ARTHUR R. ELLIOTT
Journal: JAMA (1902)

Premise: All nephritis is toxic in origin, produced by the action on the kidneys of chemical or microbial toxins. Under the name chronic nephritis are described slow inflammatory processes affecting both kidneys, due to a pathologic condition of the blood and leading to destruction of the parenchyma, with eventual shrinking of the organs. The most characteristic phenomenon of this affection, as pointed out by Senator, is not its termination in atrophy, but its casual relationship with hematic dyscrasia, for atrophy is met in other renal disease, as, for instance, in ascending nephritis. The cleansing of the blood of its impurities devolves mainly on the kidneys and it seems, therefore, evident that an abnormal condition of that fluid must be the chief source of renal affections. What the special form of hematic dyscrasia is that gives rise to lesions of the kidney, remains as yet unknown. It seems plain that the
ON THE INFLUENCE OF THE REACTION AND OF DESICCATION UPON OPSONINS
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1907)

Opsonins reveal their maximum action in a medium of neutral reaction. No opsonization takes place in a serum which contains an amount of alkali corresponding to more than 1.6 c.c. of a 1/20 N. solution, or acid more than 0.5 c.c. of this concentration per 1 c.c. of serum. Of several normal blood serums titrated (lacmoid used as indicator) the average alkalinity was found to be equivalent to about 0.8 c.c. of 1/20 N. solution. The opsonic index obtained in the native serums is not the expression of the action of the whole content of opsonins, but only so much as the degree of optimum of the reaction permits to come into action. Estimation of the opsonic power should, therefore, be made in a medium of neutral reaction and in diluted serum. All serums have their opsonic power increased by diminishing the native alkalinity. Opsonins whose activity is suspended by an unfavorable reaction become immediately active as soon as the reaction is brought back to the neutral point, unless the acid or alkali employed approaches the strength of 1 N., at which point the alteration becomes permanent. Treatment of a serum with alcohol robs it of its opsonic power. The opsonic power of serum remains unaltered upon desiccation at 23 degrees C. In the dry state opsonins are preserved for two years. The temperatures of 100 degrees , 120 degrees , 135 degrees and 150 degrees C. do not destroy opsonins of the dried serum. Complements of serum are also siccostabile and are preservable in that state for several months. Dry heat of 135 degrees C. reduces but does not destroy the complementary power of the dried serum. The opsonins and complements of the dried serum regain their original thermolability when they are dissolved in a proper amount of water. Lastly, it may be emphasized that opsonins exhibit in their sensitiveness to reaction and resistance in the dry state to high temperatures certain properties characteristic of the ferments.
Correction of interleukin-2 production in patients with systemic lupus erythematosus by removal of spontaneously activated suppressor cells.
Authors: M Linker-Israeli, A C Bakke, F P Quismorio, D A Horwitz
Journal: Journal of Clinical Investigation (1985)

Interleukin-2 (IL-2) production in vitro is depressed in systemic lupus erythematosus (SLE) patients. It is not known whether this abnormality is caused by a defect in the producer lymphocytes or by excessive suppression. We report that removal of OKT8 (Leu 2a)+ cells increased the IL-2 production by in vitro-stimulated lymphocytes to normal or above normal levels in 19 of 21 SLE patients. This increase was more apparent in those patients with clinically inactive disease and/or receiving less than 7.5 mg of prednisone. Removal of OKT8+ cells from normals did not significantly increase IL-2 activity. SLE, but not normal, OKT8+ cells decreased IL-2 production when added back to autologous OKT8-depleted cells. In some experiments, OKT8+ cells from normal donors also suppressed IL-2 production in SLE. This result suggests that the defect in IL-2 production is complex and may involve multiple cell interactions. Three lines of evidence suggest that the SLE OKT8+ cells actively inhibit the production of IL-2 rather than passively absorb this lymphokine: (a) only 3.2% of SLE lymphocytes expressed IL-2 receptors as detected with anti-Tac; (b) freshly prepared SLE lymphocytes did not absorb IL-2; and (c) cell-free supernatants from SLE OKT8+ cells inhibited IL-2 production, but not IL-2 activity. Double-labeling studies by flow cytometry revealed that 19.3% of SLE OKT8+ cells were also Ia-positive, and approximately 33% co-expressed the natural killer cell marker, HNK-1 (Leu 7). Removal of Leu 7+ cells also significantly elevated IL-2 production in SLE. These studies suggest that one or more circulating mononuclear cell subsets in SLE patients can suppress IL-2 production and that one subset may possibly belong to a non-T, non-B "third mononuclear population."
Meta-analysis: Effect of Monotherapy and Combination Therapy with Inhibitors of the Renin–Angiotensin System on Proteinuria in Renal Disease
Authors: Regina Kunz, Chris Friedrich, Marcel Wolbers, Johannes F.E. Mann
Journal: Annals of Internal Medicine (2008)

Background: Reduction of proteinuria is associated with delayed progression of chronic kidney disease. Reports suggest that angiotensin-receptor blockers (ARBs) reduce proteinuria, but results are variable. The relative effect of ARBs and angiotensin-converting enzyme (ACE) inhibitors, and their combined administration, remains uncertain. Purpose: To establish the effect of ARBs versus placebo and alternative treatments, and the effect of combined treatment with ARBs and ACE inhibitors, on proteinuria. Data Sources: English-language studies in MEDLINE and the Cochrane Library Central Register of Controlled Trials (January 1990 to September 2006), reference lists, and expert contacts. Study Selection: Randomized trials of ARBs versus placebo, ACE inhibitors, calcium-channel blockers, or the combination of ARBs and ACE inhibitors in patients with or without diabetes and with microalbuminuria or proteinuria for whom data were available on urinary protein excretion at baseline and at 1 to 12 months. Data Extraction: Two investigators independently searched and abstracted studies. Data Synthesis: Forty-nine studies involving 6181 participants reported results of 72 comparisons with 1 to 4 months of follow-up and 38 comparisons with 5 to 12 months of follow-up. The ARBs reduced proteinuria compared with placebo or calcium-channel blockers over 1 to 4 months (ratio of means, 0.57 [95% CI, 0.47 to 0.68] and 0.69 [CI, 0.62 to 0.77], respectively) and 5 to 12 months (ratio of means, 0.66 [CI, 0.63 to 0.69] and 0.62 [CI, 0.55 to 0.70], respectively). The ARBs and ACE inhibitors reduced proteinuria to a similar degree. The combination of ARBs and ACE inhibitors further reduced proteinuria more than either agent alone: The ratio of means for combination therapy versus ARBs was 0.76 (CI, 0.68 to 0.85) over 1 to 4 months and 0.75 (CI, 0.61 to 0.92) over 5 to 12 months; for combination therapy versus ACE inhibitors, the ratio of means was 0.78 (CI, 0.72 to 0.84) over 1 to 4 months and 0.82 (CI, 0.67 to 1.01) over 5 to 12 months. The antiproteinuric effect was consistent across subgroups. Limitations: Most studies were small, varied in quality, and did not provide reliable data on adverse drug reactions. Proteinuria reduction is only a surrogate for important progression of renal failure. Conclusion: The ARBs reduce proteinuria, independent of the degree of proteinuria and of underlying disease. The magnitude of effect is similar regardless of whether the comparator is placebo or calcium-channel blocker. Reduction in proteinuria from ARBs and ACE inhibitors is similar, but their combination is more effective than either drug alone. Uncertainty concerning adverse effects and outcomes that are important to patients limits applicability of findings to clinical practice.
Modifications of myelin basic protein in DM20 transgenic mice are similar to those in myelin basic protein from multiple sclerosis.
Authors: F G Mastronardi, B Mak, C A Ackerley, B I Roots, M A Moscarello
Journal: Journal of Clinical Investigation (1996)

Transgenic mice containing different numbers of transgenes (2-70) of the myelin proteolipid protein DM20 were phenotypically normal up to 3 mo of age, after which the mice containing 70 copies of the transgene spontaneously demyelinated and died at 10-12 mo. Since we demonstrated that demyelination in multiple sclerosis involved specific chemical changes in myelin basic protein (MBP), we investigated the MBP in our transgenic line for similar changes. Both the total amount of MBP in brain and the MBP mRNA levels were unaffected at the different ages. All the isoforms (14-21 kD) of MBP were present, but the microheterogeneity (a posttranslational event) was changed resulting in a higher proportion of the less cationic components reminiscent of the changes in MBP found in multiple sclerosis. An increased amount of the citrullinated form of MBP was found by Western blot analysis. Immunogold labeling of cryosections of brain revealed a greater density of particles with the anticitrulline antibody at 10 mo and that the levels of peptidylarginine deiminase (which deiminates protein-bound arginine to citrulline) were increased. This stable transgenic line represents a useful animal model for the human disease multiple sclerosis.