tbuckley/cabot-search huggingface dataset:
Mersey has changed its policy
Authors: R. C Worth, J N McGalliard, A Harley
Journal: BMJ (1995)

ED1TOR,-We agree with Helen Ward and John S Yudkin that diabetic retinopathy should not be a contraindication to the use of thrombolysis in myocardial infarction.'In September 1991 one of us (RCW) expressed concern locally that the practical difficulty of excluding diabetic retino- pathy could easily lead to diabetic patients being denied thrombolysis.The need for a rapid decision, often without the benefit of case notes and after opiate analgesia, posed particular problems for the receiving team.Subsequently, discussion took place in Mersey region among diabetologists, ophthalmologists, and cardiologists in their respective subcommittees of the regional medical committee.It was agreed that diabetic retinopathy should no longer be regarded as a contraindication to thrombolysis for two reasons: firstly, the potential benefits of a
A phase 1 dose escalation and pharmacokinetic (PK) trial of weekly docetaxel combined with daily erlotinib in adult cancer patients
Authors: C. Sweeney, J. Porter, L. Mann, C. Yoder, K. Fife, D. Murry
Journal: Journal of Clinical Oncology (2005)

2038 Background: This study aimed to define the maximum tolerated dose (MTD) of weekly docetaxel combined with daily erlotinib. Methods: 25 patients (pts) with no more than one prior therapy for metastatic disease and no prior taxane exposure were enrolled. All pts received 150 mg of oral erlotinib daily and docetaxel over 30 mins on days 1, 8 and 15 every 28 days with oral dexamethasone premedication (4 mg day before, of and after infusion). Plasma for PK of doecetaxel and erlotinib were obtained on day 1 of cycle (C) 2. A “3+3” design was used. In addition to the standard definitions of dose limiting toxicity (DLT) occurring in cycle 1, inability to give two docetaxel doses in C1 was deemed dose limiting. Erlotinib was given for a maximum of 12 cycles and docetaxel up to 6 cycles. Results: 91 cycles (Range: 1 to 12) have been administered to 22 evaluable pts. DLT in cycle 1: 0 of 3 pts treated at 20 mg/m2; 1 of 6 pts at 25 mg/m2: Grade (Gde) 4 enterocolitis with small bowel perforation; Another pt developed Gde 3 pulmonary toxicity (interstitial pneumonitis) in C3 that responded to corticosteroids. 0 of 3 pts treated at 30 mg/m2 had a DLT in cycle 1. 0 of 3 pts treated with 35 mg/m2 experienced a DLT and this cohort was then expanded to 10 pts. At this dose level, 3 pts required dose reduction in C2 (2 for Gde 3 neutropenia and one for Gde 3 mucositis), 1 pt was dose reduced in C 4 due to chronic diarrhea and 1 pt required a dose reduction in C3 due to Gde 1 elevation of bilirubin. 1 pt at this dose level was not evaluable due to Gilbert’s disease and was removed from study. Of the 22 evaluable pts, Gde 1/2 acneiform rash occurred in 8/12 pts respectively. The rash was ameliorated by dexamethasone premedication. Gde 1/2/3 diarrhea was observed in 10/8/2 pts. PK evaluation of docetaxel and erlotinib are ongoing. Activity included a partial response (PR) lasting 6+ months in a pt with non-small lung cancer, a PR lasting 12 + months in a pt with hepatoma and PR in 2 of 2 pts with cholangiocarcinoma lasting 4+ and 8+ months. Conclusion: Docetaxel at 35 mg/m2 and erlotinib at 150 mg daily can be given in combination but many patients require docetaxel reduction to 30 mg/m2 for subsequent cycles. Interesting activity has been seen in hepatobiliary carcinomas. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis
Buschke-Ollendorff syndrome: a novel case series and systematic review
Authors: V. Pope, L. Dupuis, P. Kannu, R. Mendoza-Londono, D. Sajic, J. So, G. Yoon, I. Lara-Corrales
Journal: British Journal of Dermatology (2015)

Buschke–Ollendorff syndrome (BOS) is a rare, often benign, autosomal skin disorder. BOS commonly presents with nontender connective tissue naevi and sclerotic bony lesions (osteopoikilosis [OPK]). Herein, we summarize the presenting features of BOS and potential associations by conducting a systematic review of the literature and summarizing a cohort seen at the Hospital for Sick Children (HSC), Toronto, Canada. PubMed was searched using the following terms: ‘BOS’; ‘dermatofibrosis lenticularis’; ‘OPK’; ‘LEMD3’; ‘elastoma’; ‘collagenoma’. Only case reports were included, without date or language restrictions. Cases were further narrowed to those where patients or their families had a combination of skin and bony lesions, or a positive genetic test. Data were summarized using frequencies. In total, 594 reports were discovered, of which 546 (92%) were excluded. The remaining 48 accounted for 164 cases. Skin lesions were noted in 24% of cases and bony lesions in 20%, while 54% of patients had both. In 1% of cases the diagnosis was made on genetic testing alone. A family history was noted in 92% of cases. All patients with spinal stenosis (2%) or shortened status (7%) had OPK. Six per cent of patients had neurological problems. However, 50% of the cohort from HSC had cognitive delays, and only cases from 2007 onwards reported cognitive delays (the prevalence was 17% among those cases). This review confirms the classical diagnostic features of BOS. In addition, it highlights a previously unreported association between a shortened stature and OPK, as well as a possible association with cognitive delays.
Multicentric penumonia caused by intravenous substances, a series of three cases
Authors: Raluca Geamalinga, Dragos Zaharia, Stefan Dumitrache-Rujinski, Miron Bogdan
Journal: European Respiratory Journal (2011)

Background:  In the past 2 years, we have encountered in our clinic an increased number of patients with multicentric pneumonia related to non-heroin intravenous drug use (so-called “ethnobotanic substances”), probably favorised by the low cost and legal status of these substances. We present three clinical cases with this pathology, in the attempt not only to describe the well-known clinical picture, but to warn about the severity of this community problem related to the usage of legal etnobotanic drugs.   The clinical cases:  The three patients had a very similar clinical picture: poor social background (disorganized families, homeless, prisoners), history of intravenous drug use (especially heroin), recently using etnobotanic powders intravenously, positive HCV, negative HIV and VHB, multiple bilateral lung opacities on X-Ray, similar symptomatology (fever, dyspnea, cough with mucopurulent sputum), tricuspid valve endocarditis (confirmed by echocardiography). The bacteriological exam (hemocultures and sputum) were negative probably related to the empirical antibiotic usage prior hospitalisation. Two patients improuved slowly with antibiotic treatment. One critically ill patient died with septic shock and multiple organ insufficiency.   Conclusions:  The increased number of cases with multicentric pneumonia and endocarditis related to the usage of the ethnobotanic drugs of legal status reveal their harmful effect when used intravenously.
Heparanase enhances ERK signaling and invasion of endothelial cells
Authors: Toru Uyama, Ralph Sanderson
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3099 

Heparan sulfate proteoglycans (HSPG) are ubiquitous molecules expressed on the cell surface and in extracellular matrices, and play diverse roles in a number of biological events by regulating growth factors and adhesion molecules. Recently, the importance of HSPG and its modifying enzyme, heparanase (HPSE), have been implicated in the development of cancers such as multiple myeloma. HPSE is a heparan sulfate degrading-enzyme that generates small but still active heparan sulfate fragments, and the expression level of HPSE correlates with poor prognosis of several cancers. Our lab has demonstrated that when myeloma cells are engineered to express high levels of HPSE, they exhibit a dramatic increase in tumor size and in the number and size of microvessels as compared to controls. However, the mechanism by which HPSE regulates myeloma tumor behavior remains unclear. To examine this, conditioned media from the CAG myeloma cell line expressing either HPSE or a enzymatically inactive mutant form of HPSE were harvested and incubated with human umbilical vein endothelial cells (HUVEC). The conditioned media from HPSE-expressing cells significantly enhanced ERK signaling and promoted the invasion of endothelial cells in boyden chamber assays. These effects were abolished by treatment of conditioned media with bacterial enzymes that extensively degrade heparan sulfate, suggesting that the heparanase generated fragments of heparan sulfate present in the media are at least in part responsible for stimulation of the HUVEC cells. This is also supported by the finding that conditioned media from cells bearing HPSE lacking enzyme activity do not stimulate the HUVECs. In addition, use of heparin-agarose to remove heparan sulfate-binding growth factors from conditioned media of HPSE-expressing cells completely abolished ERK signaling and invasion of endothelial cells. Together these results indicate that the dramatic increase in myeloma tumor size and microvessel density occuring in mice inoculated with cells expressing high levels of HPSE are likely due to fragments of heparan sulfate generated by HPSE. These fragments appear to regulate ERK signaling and invasion of endothelial cells by facilitating the activity of heparan sulfate-binding growth factors.
Sepsis and the Global Burden of Disease in Children
Authors: Niranjan Kissoon, Timothy M. Uyeki
Journal: JAMA Pediatrics (2015)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
An approach to conducting epidemiologic research within cooperative clinical trials groups.
Authors: S Grufferman, E Delzell, E R Delong
Journal: Journal of Clinical Oncology (1984)

Cooperative clinical trials groups offer exciting opportunities for conducting epidemiologic research for several reasons: they facilitate accrual of sufficient numbers of subjects in a short period of time, even for studies of rare diseases; they provide uniform pathologic review and uniform collection of subjects' entry data; and they provide a more representative sample of cases than a single-institution study. Despite these advantages, few epidemiologic studies of etiologic factors have been done through these groups because methods for selecting appropriate control subjects and for obtaining information from geographically scattered subjects have not been available. An approach that can serve as a model for this type of research has been developed. A collaborative case-control study of childhood rhabdomyosarcoma (RMS) with the Intergroup Rhabdomyosarcoma Study (IRS) was recently begun. The study, which is independently funded, evaluates the role of environmental factors in the etiology of RMS. Parents of subjects were interviewed by telephone and control subjects were selected from the same communities as patients by random digit dialing . Interview data are supplemented by information from birth certificates and, for patients, by IRS data. This new methodology permits a large study of a rare tumor in a relatively short period of time.
DoesHelicobacter pyloriinfection modify lung development, height or simply reflect shared environmental exposures?
Authors: Andrew W Fogarty
Journal: Thorax (2015)

The identification of Helicobacter pylori as a pathogen associated with gastric disease has led to serological assays that can establish exposure in larger study populations and hence exploration of associations with diseases epidemiologically. The paper by Sze et al ,1 is an elegant example of this process. The authors have used the data from the Lung Health Study, which is a large prospective cohort based on a randomised trial of a smoking cessation intervention coupled with an ipratropium inhaler2 that evaluated data on 4765 patients with mild to moderate COPD at baseline, who were followed up for 11 years. The ascertainment of H. pylori status was made serologically after 5 years of follow-up, and then cross-sectional associations and longitudinal changes in lung function over 11 years were examined stratified by H. pylori status. The results are that absolute lung function is lower in individuals with evidence of exposure to H. …
Abstract 19397: Poor Appetite or Overeating Predict Shorter Survival in Chronic Systolic Heart Failure
Authors: Bodo Warrings, Stefan Störk, Götz Gelbrich, Stefan Frantz, Roland Jahns, Sven Piepenburg, Ilknur Saglam, Georg Ertl, Christiane Angermann, Hermann Faller
Journal: Circulation (2012)

Introduction: Chronic systolic heart failure (CHF) is a major cause of death and hospitalization. There is growing interest in psychosomatic factors impacting on outcome in CHF. Both obesity and cachexia were shown to influence the outcome of CHF patients. We investigated the prevalence and prognostic impact of eating disorders (reduced appetite or overeating) on mortality risk in CHF. Hypothesis: Reduced appetite or overeating predict reduced survival in CHF. Methods: 864 patients hospitalized for cardiac decompensation with left ventricular ejection fraction &lt;40% (mean age 67 years, 72% male,) were examined after best possible recompensation prior to discharge using the Patient Health Questionnaire (PHQ-9). The PHQ-9 is a 9-item self-administered questionnaire for identification and semi-quantitative assessment of suspected depression. Question #5 addresses poor appetite or overeating. The survival status was reassessed after a median follow-up of 18 months. Cox proportional hazards regression was used to determine the relationship between reported poor appetite or overeating and survival. Results: At baseline, poor appetite or overeating were reported “not at all” by 403 patients (figure, line 1), “on several days” by 272 patients (line 2), “more than half of all days” by 81 patients and (line 3), “nearly every day” by 101 patients (line 4). At follow-up, 156 patients (18%) had died. All-cause mortality risk was increased in all patient groups with eating disorders: hazard ratio(line 4) 2.7 (95%CI 1.7-4.2; p&lt;0.001), HR(line 3) 2.6 (95%CI 1.6-41.2; p&lt;0.001), HR(line 2) 1.5 (95%CI 1.0-2.3; p=0.03). These results remained significant also in multivariable analysis adjusting for the other 8 PHQ-9 items. Conclusion: Eating disorders with reduced or absent appetite or overeating represent powerful prognostic indicators regarding all-cause mortalityrisk in patients with CHF hospitalized for cardiac decompensation.
Factors associated with implausible estimates of alveolar nitric oxide concentration
Authors: Sandrah Eckel, Noa Molshatzki, Edward Rappaport, Rima Habre, William Linn, Kiros Berhane, Yue Zhang, Frank Gilliland
Journal: European Respiratory Journal (2014)

INTRODUCTION: The fractional concentration of exhaled nitric oxide (FeNO) is a biomarker of airway inflammation, typically measured at a 50 ml/s flow rate (FeNO 50 ). FeNO measured at multiple flow rates can be used to non-invasively estimate the concentration of NO in the distal alveolar region (C A NO). Regardless of estimation method, researchers consistently have problems estimating C A NO for some study subjects. Non-physiologic negative C A NO estimates are often set to 0 or excluded.  AIMS: To identify factors associated with implausible estimates of C A NO.  METHODS: In March-June 2010, multiple flow FeNO was assessed in 1507 schoolchildren, ages 12-15, from the Southern California Children9s Health Study using 3 EcoMedics analyzers (CLD88-SP with DeNOx). C A NO was estimated using 3 methods. An estimate of C A NO was “problematic” if negative or 0 (for constrained methods). Associations between an indicator of problematic C A NO and testing factors/patient characteristics were evaluated using logistic regression.  RESULTS: 131 children (8.7%) had problematic C A NO for ≥ 1 method and 77 children (5.1%) had problematic C A NO for all methods. While problematic C A NO was associated with avoidable testing factors (e.g., 1 analyzer with known zero instability) there were also robust associations with: body mass index (odds ratio (OR) of 2.2 per 10 kg/m2 increase, 95% CI: 1.2, 3.9), level of FeNO 50  (OR of 1.3 per 10 ppb increase, 95% CI: 1.2, 1.45), and the slope of the 3-second “plateau” of NO concentration versus time at 300 ml/s.  CONCLUSIONS: Exclusion of subjects with negative C A NO may induce selection bias. The study of problematic C A NO may aid the development of guidelines for multiple flow FeNO assessment.
Young Age Increases Risk of Lymph Node Positivity in Early-Stage Rectal Cancer
Authors: Joshua E. Meyer, Steven J. Cohen, Karen J. Ruth, Elin R. Sigurdson, Michael J. Hall
Journal: JNCI Journal of the National Cancer Institute (2015)

The risk of lymph node positivity (LN+) in rectal cancer is a parameter that impacts therapeutic recommendations. We aimed to quantify the effect of younger age on LN+ in rectal cancer. Using the Surveillance, Epidemiology, and End Results (SEER) database, patients with rectal cancer diagnosed between 1988 and 2008 were identified. Patients were stage I-III, without preoperative radiotherapy, at least one lymph node examined, and a standard rectal cancer operation performed. The association of age and LN+ status was examined with logistic regression separately for each T stage, adjusting for multiple covariates. Poisson regression was used to evaluate age and number of positive lymph nodes (LNs). All statistical tests were two-sided. Fifty-six thousand seventy-six patients were identified, including 1194 (2.1%) patients age 20 to 39 years at diagnosis and 4199 (7.5%) patients age 40 to 49 years (defined as young). For each T stage, LN+ was inversely associated with age (all P < .001). For T1, T2, and T3, age remained predictive of LN+ status after adjustment for number of LNs examined and other covariates (P < .001 for each stage). Adjusted odds ratios (ORs) for LN+ for age 20 to 39 vs 60 to 69 were: T1: 1.97 (95% confidence interval [CI] = 1.36 to 2.86); T2: 1.48 (95% CI = 1.13 to 1.95); T3: 1.30 (95% CI = 1.10 to 1.53). Young age was a statistically significant predictor of an increased number of LNs positive for stage T2 (P = .042) and T3 (P = .002). In this large national dataset, young age at diagnosis is associated with an increased risk of LN+. This finding merits further investigation and may ultimately impact treatment decision-making for young early-stage patients.
Biomarker development for immuno-oncology and cancer immunotherapy: simultaneous digital counting of nucleic-acids and proteins at 800-plex
Authors: Alessandra Cesano, Joseph M Beechem
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The ability of mutated cells to give rise to pathological cancer relies upon the capability of these cells to interact with the immune system and ultimately evade immune recognition and suppress immune activity through multiple (differently expressed) mechanisms. Although our
Abstract 12325: Compensatory Increase of Left Atrial External Work to Left Ventricular Dysfunction During Afterload Increase: Insights Into the Mechanism of Decompensation in Heart Failure With Preserved Ejection Fraction
Authors: Katsuji Inoue, Toshihiko Asanuma, Kasumi Masuda, Daisuke Sakurai, Masamichi Oka, Koichiro Kotani, Jitsuo Higaki, Satoshi Nakatani
Journal: Circulation (2014)

Introduction: Afterload mismatch is considered as a cause of acute decompensation in patients with heart failure with preserved ejection fraction (HFPEF). However, behaviors of left atrium (LA) and ventricle (LV) to afterload increase have not been fully elucidated. We investigated how LA and LV acted to acute increase in afterload using speckle tracking echocardiography. Methods: Serial echocardiographic and hemodynamic data were acquired in 10 dogs during banding of the descending aorta (AoB). LA pressure was measured by a micromanometer via left pulmonary vein. As shown in Figure, peak negative strain during LA contraction and strain change during LA relaxation (early reservoir strain) and that during systole (late reservoir strain) were generated by simultaneous acquisition of LA longitudinal strain and volume. Pressure-strain curve showed 2 loops (A-loop, V-loop) and areas in A-loop and V-loop were computed as the work during active contraction and relaxation (A-work) and that during passive filling and emptying (V-work), respectively. Results: AoB increased LV systolic pressure by about 60 mmHg, mean LA pressure (3.8±1.3 vs. 7.1±2.0 mmHg) and LV end-diastolic pressure (4.5±1.7 vs. 10.7±4.0 mmHg, all p &lt; 0.01). LV global circumferential strain decreased (-18.8±3.5 vs. -13.2±3.5%, p &lt; 0.01) but LV stroke volume was maintained (8.4±2.3 vs. 9.6±3.6 ml). LA peak negative strain (-2.9±2.3 vs. -9.8±4.0%, p &lt; 0.01) and early reservoir strain (3.4±1.1 vs. 7.8±2.6%, p &lt; 0.01) increased substantially by AoB, but late reservoir function did not change (9.3±3.5 vs. 6.1±2.0%). A-work significantly increased (3.2±2.0 to 19.2±15.1 mmHg %, p &lt; 0.01), while V-work did not change (13.3±7.1 vs. 13.6±8.0 mmHg %). Conclusions: During aortic banding, LA contraction, early reservoir function and thereby external work during the phase increased as a compensation to LV dysfunction. The failure of this mechanism may lead to decompensation in HFPEF.