tbuckley/cabot-search huggingface dataset:
Miliary tuberculosis following homograft valve replacement.
Authors: C H Anyanwu, E Nassau, M Yacoub
Journal: Thorax (1976)

Postoperative septicaemia with infective endocarditis is a recognized complication of open-heart surgery, in particular homograft or prosthetic replacement of cardiac valves. Several infective organisms, both bacterial and fungal, have been incriminated but infection due to tubercle bacilli has not, to our knowledge, been reported. The clinicopathological features of this condition are discussed. During a five-year period, over 800 homograft replacements in the aortic and/or mitral positions have been performed at Harefield Hospital. Seven cases of miliary tuberculosis following homograft valve replacement are descrbied here. In three, there was a past history suggestive of tuberculosis infections but necropsy failed to reveal any caseous or other tuberculous lesion apart from recent miliary tuberculosis. Vegetations on the homograft valves contained microcolonies of acid-fast bacilli in most cases. Tubercle bacilli of the human type were recovered by culture or guinea-pig inoculation in six of the seven cases, and in three the diagnosis was established during life; two of these survived on antituberculosis chemotherapy. The onset of symptoms varied from a few weeks to 12 months after operation. The main presenting symptom was intermittent pyrexia. In two patients the diagnosis was made on radiological and clinical grounds and in both, tubercle bacilli were grown from drill biopsy specimens of lung tissue. The source of infection was presumed to be the homograft valves contaminated in the postmorten room. The antibiotic mixture used in the sterilization of the homografts was not effective against tubercle bacilli.
Abatacept in subjects who switch from intravenous to subcutaneous therapy: results from the phase IIIb ATTUNE study
Authors: Edward Clark Keystone, Joel M Kremer, Anthony Russell, Jane Box, Carlos Abud-Mendoza, Mario Garza Elizondo, Allison Luo, Richard Aranda, Ingrid Delaet, Rene Swanink, Sheila Gujrathi, Michael Luggen
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To assess safety, immunogenicity and efficacy in rheumatoid arthritis (RA) patients switched from long-term intravenous to subcutaneous (SC) abatacept. <h3>Methods</h3> In this phase IIIb, open-label, single-arm trial, patients who completed ≥4 years of intravenous abatacept (in long-term extensions of two phase III studies) were enrolled to receive SC abatacept (125 mg/week). The primary objective was safety during the first 3 months after switching from intravenous therapy. <h3>Results</h3> 123 patients entered the study (mean Disease Activity Score 28 (based on C reactive protein) and HAQ-DI of 3.4 and 0.94, respectively). At month 3, 120 (97.6%) patients were continuing to receive SC abatacept; no patients discontinued due to lack of efficacy. Adverse events (AEs) were reported in 49 (39.8%) patients through month 3. One patient (0.8%) discontinued due to an AE and one patient (0.8%) experienced a serious AE. Two (1.6%) patients had SC injection site reactions (erythema, pain), both with mild intensity. Clinical efficacy was maintained throughout. Limited impact on immunogenicity was observed when switching routes of administration. <h3>Conclusion</h3> These data demonstrate that patients can switch from long-term monthly intravenous abatacept to a weekly fixed dose of 125 mg SC abatacept with no increased safety concerns. This study further supports SC abatacept as an alternative treatment option for patients with RA.
Pilot Study of Televideo Psychiatric Assessments in an Underserviced Community
Authors: Annette Stevens, Norman Doidge, David Goldbloom, Peter Voore, John Farewell
Journal: American Journal of Psychiatry (1999)

The goal of this study was to evaluate patient and physician acceptance of televideo interviews for general psychiatric assessments.DSM-III-R diagnoses for axes I and II were made for 40 patients by using the Structured Clinical Interview for DSM-III-R. The patients were then randomly assigned to face-to-face or televideo interviews for general psychiatric assessments conducted by psychiatrists. After each interview the patient and psychiatrist completed measures evaluating perceived rapport and level of satisfaction with the interview.The patients gave high ratings to both satisfaction and ability to develop rapport for both the televideo and face-to-face interviews. The psychiatrists expressed significantly less satisfaction with the televideo interviews, but their actual ratings were positive.Despite geographic distance, televideo interviews allow a sense of connection between patient and psychiatrist. Lower-cost technology may increase the use of televideo to extend psychiatric service to geographically isolated communities.
Origin of Parietal Podocytes in Atubular Glomeruli Mapped by Lineage Tracing
Authors: Kevin Schulte, Katja Berger, Peter Boor, Peggy Jirak, Irwin H. Gelman, Kenton P. Arkill, Christopher R. Neal, Wilhelm Kriz, Jürgen Floege, Bart Smeets, Marcus J. Moeller
Journal: Journal of the American Society of Nephrology (2013)

Parietal podocytes are fully differentiated podocytes lining Bowman's capsule where normally only parietal epithelial cells (PECs) are found. Parietal podocytes form throughout life and are regularly observed in human biopsies, particularly in atubular glomeruli of diseased kidneys; however, the origin of parietal podocytes is unresolved. To assess the capacity of PECs to transdifferentiate into parietal podocytes, we developed and characterized a novel method for creating atubular glomeruli by electrocoagulation of the renal cortex in mice. Electrocoagulation produced multiple atubular glomeruli containing PECs as well as parietal podocytes that projected from the vascular pole and lined Bowman's capsule. Notably, induction of cell death was evident in some PECs. In contrast, Bowman's capsules of control animals and normal glomeruli of electrocoagulated kidneys rarely contained podocytes. PECs and podocytes were traced by inducible and irreversible genetic tagging using triple transgenic mice (PEC- or Pod-rtTA/LC1/R26R). Examination of serial cryosections indicated that visceral podocytes migrated onto Bowman's capsule via the vascular stalk; direct transdifferentiation from PECs to podocytes was not observed. Similar results were obtained in a unilateral ureter obstruction model and in human diseased kidney biopsies, in which overlap of PEC- or podocyte-specific antibody staining indicative of gradual differentiation did not occur. These results suggest that induction of atubular glomeruli leads to ablation of PECs and subsequent migration of visceral podocytes onto Bowman's capsule, rather than transdifferentiation from PECs to parietal podocytes.
Phase I Clinical Trial of Cilengitide in Children With Refractory Brain Tumors: Pediatric Brain Tumor Consortium Study PBTC-012
Authors: Tobey J. MacDonald, Clinton F. Stewart, Mehmet Kocak, Stewart Goldman, Richard G. Ellenbogen, Peter Phillips, Deborah Lafond, Tina Young Poussaint, Mark W. Kieran, James M. Boyett, Larry E. Kun
Journal: Journal of Clinical Oncology (2008)

Purpose A phase I trial of the antiangiogenesis agent cilengitide (EMD 121974), an alpha v beta 3,5 integrin antagonist, was performed to estimate the maximum-tolerated dose (MTD) and describe dose-limiting toxicities (DLTs) and the incidence and severity of other toxicities when administered to children with refractory brain tumors. Patients and Methods Thirty-one assessable patients received intravenous cilengitide over 1 hour twice a week for up to 52 weeks at dosages from 120 to 2,400 mg/m 2 . Serial blood and urine samples for clinical pharmacology studies were obtained in a subset of consenting patients. Results No DLTs were observed, and thus, the MTD was not estimated. Three of 13 patients at the dosage level of 2,400 mg/m 2 experienced grade 3 or 4 intratumoral hemorrhage (ITH) possibly related to the study drug; however, two of the ITH events were asymptomatic and, by the current toxicity criteria, would be classified as grade 1. For patients treated at cilengitide 2,400 mg/m 2 , the 6-month cumulative incidence estimate of ITH is 23% (SE = 13%). No ITH was observed at 1,800 mg/m 2 . Three patients completed 1 year of protocol therapy; one patient with glioblastoma multiforme demonstrated complete response, and two patients had stable disease (SD). An additional patient had SD for more than 5 months. Conclusion The phase II dosage of intravenous cilengitide in children with refractory brain tumors is 1,800 mg/m 2 . A phase II trial to assess the efficacy of cilengitide therapy for children with refractory brain tumors is being developed by the Children's Oncology Group.
Plasma atrial natriuretic factor and cyclic GMP in mitral stenosis treated by balloon valvulotomy. Effect of atrial fibrillation.
Authors: J C Dussaule, A Vahanian, P L Michel, I Soullier, S Czekalski, J Acar, R Ardaillou
Journal: Circulation (1988)

To study the relation between plasma atrial natriuretic factor (ANF) and cardiac pressures, we measured plasma ANF in 24 patients with mitral stenosis 30 minutes before and 20 minutes after balloon mitral valvulotomy. All patients were without physical signs of congestive heart failure. Normal sinus rhythm was present in 15 (group 1), whereas the other nine (group 2) had permanent atrial fibrillation. There were no significant differences between groups for basal mean pressures in right atrium (RA), left atrium (LA), and pulmonary artery (PA). Valvulotomy resulted in a fall in both groups (p less than 0.001) in LA and PA mean pressures, whereas heart rate, cardiac index, and RA and aorta (AO) pressures did not change significantly. Basal ANF was not different in either group in RA (240 +/- 43 vs. 266 +/- 35 pg/ml) or AO (441 +/- 92 vs. 643 +/- 70 pg/ml) but tended to be higher in group 2 in LA (428 +/- 88 vs. 682 +/- 84 pg/ml; p = 0.059) and PA (488 +/- 93 vs. 759 +/- 92 pg/ml; p = 0.057). Plasma ANF was the highest in PA, and about 50% ANF was extracted in the systemic circulation. After valvulotomy, plasma ANF was greater (p less than 0.05) in group 2 (372 +/- 90, 755 +/- 152, 805 +/- 134, and 707 +/- 144 pg/ml) than in group 1 (206 +/- 36, 386 +/- 47, 429 +/- 66, and 421 +/- 49 pg/ml), regardless of the site of blood collection (RA, LA, PA, and AO, respectively). PA ANF was correlated with LA pressure (p less than 0.05) in group 1 before as well as after valvulotomy, whereas there was no such correlation in group 2. Cyclic GMP (cGMP) in LA was correlated (p less than 0.01) with PA ANF in group 1, and LA cGMP (10.0 +/- 1.2 and 9.1 +/- 1.8 pmol/ml in groups 1 and 2, respectively) was higher (p less than 0.05) than PA cGMP (9.1 +/- 1.0 and 8.0 +/- 1.5 pmol/ml in groups 1 and 2, respectively) before valvulotomy, which suggests the presence of ANF receptors in the pulmonary circulation. Taken together, these results indicate that in patients in sinus rhythm with mitral stenosis, there is an increase in ANF secretion depending on LA pressure. ANF secretion is also high in patients with mitral stenosis and atrial fibrillation but does not respond appropriately to changes in LA pressure.(ABSTRACT TRUNCATED AT 400 WORDS)
Temporary Hemiplegia from Cerebral Injection of Diodrast during Catheter Aortography
Authors: E. CONVERSE PEIRCE
Journal: Circulation (1953)

Brain damage manifested by convulsions, hemiplegia, or death may result whenever concentrated Diodrast is injected into the cerebral circulation. Reactions are fairly common following cerebral giography but may follow contrast visualization of the thoracic aorta by any method. The greatest danger is in aortography when the maximum dye concentration is in the aortic arch. The reactions probably do not result from vascular spasm but from an alteration in the blood-brain barrier. It is possible to minimize the danger of reactions in aortography by observing certain simple precautions. Treatment of brain damage when it occurs, however, is not satisfactory.
Akt Mediates the Cross-Talk Between β-Adrenergic and Insulin Receptors in Neonatal Cardiomyocytes
Authors: Carmine Morisco, Gerolama Condorelli, Valentina Trimarco, Alessandro Bellis, Chiara Marrone, Gianluigi Condorelli, Junichi Sadoshima, Bruno Trimarco
Journal: Circulation Research (2005)

Upregulation of the sympathetic nervous system plays a key role in the pathogenesis of insulin resistance. Although the heart is a target organ of insulin, few studies have examined the mechanisms by which β-adrenergic stimulation affects insulin sensitivity in cardiac muscle. In this study, we explored the molecular mechanisms involved in the regulation of the cross-talk between β adrenergic and insulin receptors in neonatal rat cardiomyocytes and in transgenic mice with cardiac overexpression of a constitutively active mutant of Akt (E40K Tg). The results of this study show that β-adrenergic receptor stimulation has a biphasic effect on insulin-stimulated glucose uptake. Short-term stimulation induces an additive effect on insulin-induced glucose uptake, and this effect is mediated by phosphorylation of Akt in threonine 308 through PKA/Ca 2+ -dependent and PI3K-independent pathway, whereas insulin-evoked threonine phosphorylation of Akt is exclusively PI3K-dependent. On the other hand, long-term stimulation of β-adrenergic receptors inhibits both insulin-stimulated glucose uptake and insulin-induced autophosphorylation of the insulin receptor, and at the same time promotes threonine phosphorylation of the insulin receptor. This is mediated by serine 473 phosphorylation of Akt through PKA/Ca 2+ and PI3K-dependent pathways. Under basal conditions, E40K Tg mice show increased levels of threonine phosphorylation of the β subunit of the insulin receptor and blunted tyrosine autophosphorylation of the β-subunit of the insulin receptor after insulin stimulation. These results indicate that, in cardiomyocytes, β-adrenergic receptor stimulation impairs insulin signaling transduction machinery through an Akt-dependent pathway, suggesting that Akt is critically involved in the regulation of insulin sensitivity.
Racial/Ethnic Differences in Functional Outcomes in the 5 Years After Diagnosis of Localized Prostate Cancer
Authors: Terri Kang Johnson, Frank D. Gilliland, Richard M. Hoffman, Dennis Deapen, David F. Penson, Janet L. Stanford, Peter C. Albertsen, Ann S. Hamilton
Journal: Journal of Clinical Oncology (2004)

We investigated racial/ethnic differences in functional outcomes up to 5 years after diagnosis among men with aggressively treated localized prostate cancer.Patients were from the Prostate Cancer Outcomes Study, a population-based cohort study that surveyed patients at 6, 12, 24, and 60 months after diagnosis. Analyses were stratified by primary treatment. Racial/ethnic differences at each time point were assessed using Generalized Estimating Equations, adjusting for pretreatment function, age at diagnosis, secondary treatment, and other confounders. An adjusted summary score for each functional domain was calculated for each time period.Patients included 1,475 non-Hispanic white, 321 African-American, and 279 Hispanic prostate cancer patients. After 60 months, among prostatectomy patients, African-Americans had significantly higher sexual function scores than non-Hispanic whites (43.9 v 36.1; P = .02), but were more likely to have a moderate to big problem with sexual function (50.6% v 44.4%; P = .04). African-Americans also had higher urinary function scores at 5 years than non-Hispanic whites (78.5 v 72.4; P = .04) and were less likely to have problems with incontinence. Changes in sexual and bowel function after radiotherapy showed no significant racial/ethnic differences.This long-term cohort study found that, among prostatectomy patients, African-Americans had better recovery of sexual and urinary function at 60 months after diagnosis that was likely to be of mild clinical significance, despite reporting more problems with sexual function than non-Hispanic whites. More study is necessary to understand reasons for these differences. In contrast, no racial/ethnic differences in recovery from radiotherapy were found.
Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials
Authors: J. A. C. Sterne, A. J. Sutton, J. P. A. Ioannidis, N. Terrin, D. R. Jones, J. Lau, J. Carpenter, G. Rucker, R. M. Harbord, C. H. Schmid, J. Tetzlaff, J. J. Deeks, J. Peters, P. Macaskill, G. Schwarzer, S. Duval, D. G. Altman, D. Moher, J. P. T. Higgins
Journal: BMJ (2011)

Funnel plots, and tests for funnel plot asymmetry, have been widely used to examine bias in the results of meta-analyses. Funnel plot asymmetry should not be equated with publication bias, because it has a number of other possible causes. This article describes how to interpret funnel plot asymmetry, recommends appropriate tests, and explains the implications for choice of meta-analysis model
In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling
Authors: Satoshi Nishimura, Ichiro Manabe, Mika Nagasaki, Shigeru Kakuta, Yoichiro Iwakura, Naoya Takayama, Jun Ooehara, Makoto Otsu, Akihide Kamiya, Brian G. Petrich, Tetsumei Urano, Takafumi Kadono, Shinichi Sato, Atsu Aiba, Hiroshi Yamashita, Seiryo Sugiura, Takashi Kadowaki, Hiromitsu Nakauchi, Koji Eto, Ryozo Nagai
Journal: Blood (2011)
Systematic review and evaluation of physiological track and trigger warning systems for identifying at-risk patients on the ward
Authors: Haiyan Gao, Ann McDonnell, David A. Harrison, Tracey Moore, Sheila Adam, Kathleen Daly, Lisa Esmonde, David R. Goldhill, Gareth J. Parry, Arash Rashidian, Christian P Subbe, Sheila Harvey
Journal: Intensive Care Medicine (2007)
Phase II Study of Temsirolimus in Women With Recurrent or Metastatic Endometrial Cancer: A Trial of the NCIC Clinical Trials Group
Authors: Amit M. Oza, Laurie Elit, Ming-Sound Tsao, Suzanne Kamel-Reid, Jim Biagi, Diane Michele Provencher, Walter H. Gotlieb, Paul J. Hoskins, Prafull Ghatage, Katia S. Tonkin, Helen J. Mackay, John Mazurka, Joana Sederias, Percy Ivy, Janet E. Dancey, Elizabeth A. Eisenhauer
Journal: Journal of Clinical Oncology (2011)

Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene, and loss of function mutations are common and appear to be important in the pathogenesis of endometrial carcinomas. Loss of PTEN causes deregulated phosphatidylinositol-3 kinase/serine-threonine kinase/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling which may provide neoplastic cells with a selective survival advantage by enhancing angiogenesis, protein translation, and cell cycle progression. Temsirolimus, an ester derivative of rapamycin that inhibits mTOR, was evaluated in this setting.Sequential phase II studies evaluated single-agent activity of temsirolimus in women with recurrent or metastatic chemotherapy-naive or chemotherapy-treated endometrial cancer. Temsirolimus 25 mg intravenously was administered weekly in 4-week cycles.In the chemotherapy-naive group, 33 patients received a median of four cycles (range, one to 23 cycles). Of the 29 patients evaluable for response, four (14%) had an independently confirmed partial response and 20 (69%) had stable disease as best response, with a median duration of 5.1 months (range, 3.7 to 18.4 months) and 9.7 months (range, 2.1 to 14.6 months). Only five patients (18%) had progressive disease. In the chemotherapy-treated group, 27 patients received a median of three cycles (range, one to six cycles). Of the 25 patients evaluable for response, one (4%) had an independently confirmed partial response, and 12 patients (48%) had stable disease, with a median duration of 4.3 months (range, 3.6 to 4.9 months) and 3.7 months (range, 2.4 to 23.2 months). PTEN loss (immunohistochemistry and mutational analysis) and molecular markers of PI3K/Akt/mTOR pathway did not correlate with the clinical outcome.mTOR inhibition with temsirolimus has encouraging single-agent activity in endometrial cancer which is higher in chemotherapy-naive patients than in chemotherapy-treated patients and is independent of PTEN status. The difference in activity according to prior therapy should be factored into future clinical trial designs.
Meta-Analysis of the Association Between Cigarette Smoking and Incidence of Hodgkin's Lymphoma
Authors: Jorge J. Castillo, Samir Dalia, Helen Shum
Journal: Journal of Clinical Oncology (2011)

Previous studies have suggested a relationship between smoking and Hodgkin's lymphoma (HL). The main objective of this study was to evaluate this potential association with a meta-analysis of observational studies.A literature search was undertaken through December 2010 looking for observational studies evaluating the association between smoking and HL. From 714 articles, 17 were included in this study. Outcome was calculated and reported as odds ratio (OR). Heterogeneity was assessed by using the I(2) index. Publication bias was evaluated by trim-and-fill analysis. Quality assessment was performed with the Newcastle-Ottawa scale.Our analysis showed an OR of developing HL of 1.35 (95% CI, 1.17 to 1.56; P < .001) in current smokers. Former smokers did not have an increased risk of HL. In subset analyses of current smokers, men and older individuals had ORs of HL of 1.78 (95% CI, 1.46 to 2.17; P < .001) and 1.77 (95% CI, 1.23 to 2.54; P = .002), respectively. In addition, the OR of HL was increased in individuals who smoke more than 20 cigarettes per day, have smoked more than 20 years, or have smoked more than 15 pack-years at 1.51 (95% CI, 1.16 to 1.98; P = .002), 1.84 (95% CI, 1.47 to 2.32; P < .001), and 1.97 (1.53 to 2.54; P < .001), respectively. Meta-regression analyses showed a relative OR of HL of 1.007 (95% CI, 1.001 to 1.013; P = .025) per cigarette per day and of 1.013 (95% CI, 1.006 to 1.019; P < .001) per year of smoking.Smoking seems to increase the odds of developing HL in current smokers. The risk of HL is higher in men and older individuals and increases with higher intensity and longer duration of smoking.
Immune monitoring technology primer: clinical validation for predictive markers
Authors: Kevin K. Dobbin
Journal: Journal for ImmunoTherapy of Cancer (2015)

Recent biotechnological developments have resulted in increasing interest in immunology biomarkers. These biomarkers have potential clinical utility in the near future as predictors of treatment response. Hence, clinical validation of these predictive markers is critical.The process of clinically validating a predictive biomarker is reviewed. Validation of a predictive biomarker requires quantifying the strength of a statistical interaction between marker and a treatment. Different study designs are considered.Clinical validation of immunology biomarkers can be demanding both in terms of time and resources, and careful planning and study design are critical.