tbuckley/cabot-search huggingface dataset:
Role of procalcitonin and granulocyte colony stimulating factor in the early prediction of infected necrosis in severe acute pancreatitis
Authors: C A Muller
Journal: Gut (2000)

<h3>BACKGROUND</h3> Infected pancreatic necrosis (IPN) is the main cause of death in patients with severe acute pancreatitis. Therefore an early prediction of IPN is of utmost importance. <h3>AIM</h3> Analysis of new blood variables as potential early predictors to differentiate between IPN and sterile pancreatic necrosis (SPN). <h3>PATIENTS</h3> 64 consecutive patients with acute pancreatitis were enrolled in this prospective study; 29 were suffering from acute oedematous pancreatitis (AIP), and 35 from necrotising disease (NP) as diagnosed by contrast enhanced computed tomography. <h3>METHODS</h3> Procalcitonin (PCT) and granulocyte colony stimulating factor (G-CSF) in the serum were examined and compared with C reactive protein (CRP). CRP was measured with a turbidimetric immunoassay (Autokit CRP; Wako, Osaka, Japan), and PCT and G-CSF by ELISA (Lumitest PCT; Brahms Diagnostica, Berlin, Germany; G-CSF-Elisa; R&amp;D Systems, Abingdon, Oxon, UK). Monitoring was performed daily and related to the onset of symptoms. <h3>RESULTS</h3> Within the first week, all three variables (CRP, PCT, and G-CSF) were significantly higher in patients with NP than in those with AIP (CRP, p&lt;0.001; G-CSF, p&lt;0.001; PCT, p&lt;0.001). During the course of the study, 12 of the 35 patients with NP developed late IPN after a median of 20.5 (range 3–49) days. Neither the peak nor the lowest concentrations during the monitoring period were of any value for predicting IPN (median peak values in SPN <i>v</i>IPN: PCT, 0.93 <i>v</i> 1.93 ng/ml; G-CSF, 347<i>v</i> 421 pg/ml; CRP, 270<i>v</i> 325 mg/l). <h3>CONCLUSIONS</h3> Serum PCT, G-CSF, and CRP concentrations are of similar value for early differentiation between mild and severe acute pancreatitis. However, these variables are not suitable for the early prediction of IPN.
Proliferation of Ductal Outgrowths by Carcinogen-Induced Rat Mammary Tumors in Gland-Free Mammary Fat Pads&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: E M Rivera, S Vijayaraghavan
Journal: JNCI Journal of the National Cancer Institute (1982)

The purpose of this study was to evaluate the gland-free mammary fat pad as a preferential site for transplantation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors, since previous studies indicated their frequent failure to grow when transplanted in ectopic sites. Accordingly, samples from 14 primary mammary tumors (9 randomly selected and 5 ovarian-independent) were transplanted into the inguinal pairs of gland-free mammary fat pads of syngeneic female Lewis rats (9-12 wk of age). Although the percentage of takes was high (88%), the growth and morphogenetic capabilities of the transplants were strikingly different. Whereas transplants of ovarian-independent tumors consistently developed palpable carcinomas, transplants of all but 1 of the tumors selected at random (most of which were presumably ovarian-dependent) gave rise mainly to apparently normal ductal and hyperplastic outgrowths. The growth behavior of the transplants could not be correlated with the presence or absence in the tumors of mononuclear cells of the immune system. Unless the mammary fat pad selected against the growth of tumor cells, it seemed that the main alternative to tumor formation by the transplants was the proliferation of nontumorous outgrowths. These results draw attention to differences in the phenotypic stability of primary mammary tumors induced by DMBA and open up for further study the question of whether these differences reflect their cellular heterogeneity or their potential to undergo differentiation.
Phase II Trial of Neoadjuvant Vincristine, Ifosfamide, and Doxorubicin With Granulocyte Colony-Stimulating Factor Support in Children and Adolescents With Advanced-Stage Nonrhabdomyosarcomatous Soft Tissue Sarcomas: A Pediatric Oncology Group Study
Authors: Alberto S. Pappo, Meenakshi Devidas, Jessee Jenkins, Bhaskar Rao, Robert Marcus, Patrick Thomas, Mark Gebhardt, Charles Pratt, Holcombe E. Grier
Journal: Journal of Clinical Oncology (2005)

To describe the response rate and survival of children and adolescents with unresected or metastatic nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) treated with vincristine, ifosfamide, and doxorubicin.Between September 1996 and June 2000, 39 eligible patients received vincristine (1.5 mg/m(2) weekly for 13 doses), ifosfamide (3 g/m(2) daily for 3 days every 3 weeks for seven cycles), doxorubicin (30 mg/m(2) daily for 2 days for six cycles), and mesna (750 mg/m(2) for four doses after ifosfamide). Granulocyte colony-stimulating factor was administered daily (5 mug/kg) after each cycle of chemotherapy. Radiotherapy was administered from weeks 7 through 12.The median patient age at diagnosis was 11.7 years; the most common primary tumor site was lower extremity (36%); and synovial sarcoma was the predominant histology. More than three fourths of all tumors were 5 cm or greater at their largest diameters. The overall objective combined partial and complete response rate was 41% (95% CI, 25.7% to 56.7%). The estimated 3-year overall survival and progression-free survival rates (+/- standard deviation) for eligible patients were 59% +/- 8.2% and 43.6% +/- 7%, respectively. Patients with clinical group III disease had significantly better 3-year and progression-free survival rates compared with patients who presented with metastatic disease.The vincristine, ifosfamide, and doxorubicin regimen was moderately active against pediatric NRSTS. Patients with synovial sarcoma had higher response rates than other patients, and patients with unresected disease had improved outcomes. Patients with metastatic disease continue to fare poorly, and newer approaches are indicated for these patients.
LSC 2011 Abstract: Role of mast cells and chymase in idiopathic pulmonary fibrosis
Authors: Djuro Kosanovic, Bhola Kumar Dahal, Josef Messinger, Yvan Fischer, Katrin Hoffmann, Jochen Antel, Bettina Husen, Nina Hanke, Stephanie Mayet, Hossein Ardeschir Ghofrani, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Ralph Theo Schermuly
Journal: European Respiratory Journal (2011)

Rationale: Mast cell (MC) activation has been implicated in the pathogenesis of inflammatory lung diseases. Among the MC-derived mediators, MC chymase is involved in the processes such as activation of TGF-β and formation of collagen fibrils. The literature suggests that chymase may contribute to the pathogenesis of pulmonary interstitial remodeling; however, a systematic investigation is still missing.

Methods: Lung tissues obtained from donors and patients with idiopathic pulmonary fibrosis (IPF) were formalin-fixed and paraffin-embedded, followed by toluidine blue staining for MCs and by immunostaining for chymase. The total, perivascular and interstitial MC and chymase-positive MC (CMC) number in each section was evaluated by using a light microscopy and computerized morphometric system. Also, MCs were separated as granulated and degranulated (activated) and index of granulation (IOG) (number of granulated/number of degranulated MCs) was determined.

Results: The quantification of pulmonary MCs and CMCs revealed that their population was about 6 and 8 folds higher in IPF patients, as compared with donors. There was a preponderance of perivascular MCs and CMCs in IPF lungs (p<0.05 versus donor lungs). Furthermore, we found that there was about 8 fold decrease of IOG in IPF patients as compared with donors. Finally, there was a strong accumulation of both MCs and CMCs in interstitial regions of the tissues (∼65%) in comparison with other regions of the lungs.

Conclusion: The findings suggest that chymase released from activated MCs may be involved in the pathogenesis of IPF. Further investigations will unravel the underlying pathomechanism and substantiate chymase as a potential target for future therapeutic strategies.
Multicenter study evaluating a dual policy of postorchiectomy surveillance and selective adjuvant single-agent carboplatin for patients with clinical stage I seminoma
Authors: J. Aparicio, X. García del Muro, P. Maroto, L. Paz-Ares, E. Alba, A. Sáenz, J. Terrasa, A. Barnadas, D. Almenar, J.A. Arranz, M. Sánchez, A. Fernández, J. Sastre, J. Carles, J. Dorca, J. Gumà, A.L. Yuste, J.R. Germà
Journal: Annals of Oncology (2003)
Bone-Derived IGF Mediates Crosstalk between Bone and Breast Cancer Cells in Bony Metastases
Authors: Toru Hiraga, Akira Myoui, Nobuyuki Hashimoto, Akira Sasaki, Kenji Hata, Yoshihiro Morita, Hideki Yoshikawa, Clifford J. Rosen, Gregory R. Mundy, Toshiyuki Yoneda
Journal: Cancer Research (2012)

Abstract The continuous release of bone-stored growth factors after bone resorption promotes the colonization of circulating cancer cells. However, the precise role of each of the various growth factors remains unclear. In this study, we investigated the role of bone-derived insulin-like growth factor (IGF) in the development of bone metastases in an animal model of breast cancer. We found that local stimulation of calvarial bone resorption before cell inoculation stimulated subsequent bone metastases to that site in vivo, although inhibition of bone resorption inhibited bone metastases. Anchorage-independent growth of cancer cells was stimulated by the culture supernatants from resorbed bones, which contained elevated levels of IGF-I. This stimulation was blocked by IGF type I receptor (IGF-IR) neutralizing antibody, but not antibody targeting other bone-stored growth factors including TGF-β, fibroblast growth factors, and platelet-derived growth factors. Although recombinant human IGF-I caused IGF-IR tyrosine autophosphorylation, followed by activation of Akt and NF-κB in cancer cells, dominant-negative inhibition of IGF-IR, Akt, or NF-κB significantly reduced bone metastases with increased apoptosis and decreased mitosis in metastatic cells. Together, our findings suggest that bone-derived IGF-I bridges the crosstalk between bone and metastasized cancer cells via activation of the IGF-IR/Akt/NF-κB pathway. Disruption of this pathway therefore may represent a promising therapeutic intervention for bone metastasis. Cancer Res; 72(16); 4238–49. ©2012 AACR.
The Initiation of Ventricular Tachycardia and Fibrillation by Procaine in the Isolated-Perfused Rabbit Heart
Authors: LEONARD GRUMBACH, V. I. Merrill
Journal: Circulation Research (1956)

An accelerating ventricular tachycardia ending in fibrillation can be initiated in isolated hearts by procaine injections after the administration of epinephrine, but not in untreated hearts. The run of tachycardia consists of a supraventricular or idioventricular impulse followed by an accelerating train of premature systoles coupled to it. Fibrillation results when the train reaches a frequency of 10 to 12 per second. In hearts with their bundles of His cut, epinephrine injections alone cause only a ventricular tachycardia of constant frequency. Therefore, the initiation of ventricular arrhythmias by procaine must entail the production of A-V blockade and some process which causes the tachycardia to accelerate.
A clone-specific monoclonal antibody that inhibits cytolysis of a cytolytic T cell clone.
Authors: D W Lancki, M I Lorber, M R Loken, F W Fitch
Journal: The Journal of Experimental Medicine (1983)

Monoclonal antibody 384.5 specifically inhibited cytolysis of P-815 target cells by cloned L3 cytotoxic T lymphocyte (CTL) effector cells. The lytic activity of other cloned CTL that have other distinct specificities was not affected. Antibody 384.5 did not inhibit the cytolytic activity of bulk populations of C57BL/6 mixed lymphocyte culture (MLC) cells. Concanavalin A-facilitated cytolysis by T cell clone L3 but not T cell clone B18 was inhibited by antibody 384.5, whereas phytohemagglutinin-facilitated cytolysis by L3 cells was not strongly inhibited. Antibody 384.5 binds specifically to L3 cells but not to several other T lymphocytes clones, or to a detectable portion of populations of primary MLC cells, normal spleen, thymus, lymph node, or bone marrow cells. In contrast, C57BL/6 anti-B10.A(5R) secondary MLC cells (genetically enriched for reactivity against the H-2Dd region gene products) contained a small population which reacted with the antibody 384.5. The determinant detected by antibody 384.5 was susceptible to trypsin treatment, and was reexpressed after overnight incubation. These results suggest that the monoclonal antibody 384.5 detects an endogenously synthesized clone-specific determinant associated with the cytolytic activity of the L3 CTL clone. These properties make antibody 384.5 an attractive candidate for an antibody that reacts with the antigen-recognition site of a cytolytic T cell antigen receptor.
Electrocardiography in suspected angina
Authors: B. Abramson
Journal: BMJ (2008)

Is poor at predicting future events, but still an essential part of assessment

In the linked cohort study (doi:10.1136/bmj.a2240), Sekhri and colleagues assess whether resting and exercise electrocardiograms (ECGs) provide superior prognostic value to that obtained from the clinical history in ambulatory patients with suspected angina.1 The study indicates that the clinical assessment accounts for most of the prognostic information provided by resting and exercise ECGs.

Other studies and algorithms have used the patient’s pretest probability to help with diagnosis,2 but long term prediction of risk and the incremental usefulness of the ECG have not been evaluated in this way. 

The study is a reminder of the importance of taking a …
Swimming and grommets.
Authors: M. B. Pringle
Journal: BMJ (1992)

Swimming and grommetsChildren with grommets should be allowed to swim Nearly 40 years after the technique of grommet insertion was than non-swimmers.Ear plugs seem to confer no extra reintroduced by Armstrong' otolaryngological advice about benefit, and the muffling of sound and the necessary adult whether children with grommets should be allowed to swim supervision decrease both the fun and the enjoyment of still varies from total prohibition to total licence.The swimming.'5The question ofwhether bath water increases the theoretical risk is that water will pass through the grommet risk of ear infection in children with grommets has not been and infect the middle ear.But does this happen?studied, though high concentrations of bacteria and irritative Morgan found that after the ears were submerged in a bath substances have been shown in bath water.'6for four minutes in only half the cases was there water on the Chapman wrote that the advice to forbid swimming in tympanic membrane.2Calculating that water pressures of children with grommets "causes distress, delays the acquisi- 12 5-22-5 cm would be needed to push water through a tion of a life-saving skill and is based on no published grommet, several authors concluded that contamination of evidence."8Twelve years and numerous studies later, this the middle ear was unlikely with normal swimming, hair statement remains true.washing, and bathing but that the risk would be increased M B PRINGLE with diving.34They suggested that the eustachian tube had to ENT Registrar, be functioning before water would pass though a grommet,5 Royal National Throat, Nose, and Ear Hospital, and Myerhoff et al confirmed this with animal experiments.6London WClX 8DAChildren with glue ear often have impaired function of the I Armstrong BW.A new treatment for chronic secretory otitis media.Arch Otolaryngol eustachian tube, thus making contamination of the middle ear 1954;49:653-4.less likely.
Declining Insulin Requirement in the Late First Trimester of Diabetic Pregnancy
Authors: Lois Jovanovic, Robert H. Knopp, Zane Brown, Mary R. Conley, Eunsik Park, James L. Mills, Boyd E. Metzger, Jerome H. Aarons, Lewis B. Holmes, Joe L. Simpson
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement. RESEARCH DESIGN AND METHODS—We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements. RESULTS—In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7–8 and ending weeks 11–12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: &amp;lt;2 SDs above the mean of a normal population (subgroup 1), 2–4 SDs (subgroup 2), and &amp;gt;4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI &amp;gt;27.0 had a greater initial insulin rise and then fall compared with leaner women. CONCLUSIONS—Observations in the DIEP cohort disclose a mid–first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation.
Emotion Regulation and Psychopathology
Authors: Gal Sheppes, Gaurav Suri, James J. Gross
Journal: Annual Review of Clinical Psychology (2015)

Emotional problems figure prominently in many clinical conditions. Recent efforts to explain and treat these conditions have emphasized the role of emotion dysregulation. However, emotional problems are not always the result of emotion dysregulation, and even when emotional problems do arise from emotion dysregulation, it is necessary to specify precisely what type of emotion dysregulation might be operative. In this review, we present an extended process model of emotion regulation, and we use this model to describe key points at which emotion-regulation difficulties can lead to various forms of psychopathology. These difficulties are associated with (a) identification of the need to regulate emotions, (b) selection among available regulatory options, (c) implementation of a selected regulatory tactic, and (d) monitoring of implemented emotion regulation across time. Implications and future directions for basic research, assessment, and intervention are discussed.
Clinical judgement on top of CURB65-score in predicting 30 days clinical outcome in patients with community acquired pneumonia (CAP) admitted to the hospital
Authors: Ruud Duijkers, Dominic Snijders, Wim Boersma
Journal: European Respiratory Journal (2014)

Background: Several scoring systems exist to determine severity and clinical outcome of CAP. Amongst those is the CURB65 score, a well established tool to guide therapy and predict mortality in these patients. We wanted to see if adding the clinical judgement of the attending physician (not ill, moderately ill, severely ill) would improve the predictive capabilities of the CURB65-score.  Methods: We used retrospective data derived from the CAPISCE study, which was a randomised controlled trial in a large teaching hospital in the Netherlands to assess the benefit of corticosteroid treatment in patients with CAP. Patients were scored ill or not ill at the time of admission by the attending physician. The CURB65 score was recorded as well. Clinical outcome was scored at day 30 as either cure or failure.  Results: Data from 197 patients was available for analysis. Below are the Area Under the Curves for the CURB65 score, CURB65 score with clinical judgement and clinical judgement alone. Adding clinical judgement to the CURB65 score did not show any benefit in predicting clinical outcome at day 30. The AUC went from 0.741 (CURB65 score alone) to 0.746 (CURB65 score and clinical judgement) with a p value of 0.93.  Conclusion: These results show that clinical judgement at time of admission is a poor predictive value for clinical outcome at day 30.
Down-regulation of c-Myc following MEK/ERK inhibition halts the expression of malignant phenotype in rhabdomyosarcoma and in non muscle-derived human tumors
Authors: Francesco Marampon, Carmela Ciccarelli, Bianca M Zani
Journal: Molecular Cancer (2006)

Expression of c-myc proto-oncogene is inappropriate in a wide range of human tumors, and is a downstream target of Ras/Raf/ERK pathway, which promotes c-Myc stability by enhancing c-Myc expression and activity. The aim of this study was to investigate whether the oncogenic phenotype in the human muscle-derived Rhabdomyosarcoma (RD) cell line and in non muscle-derived human tumor cell lines (SW403, IGR39 and PC3) can be blocked by disrupting the c-Myc pathway either by means of pharmacological MEK/ERK inhibition or by direct inactivation of the c-Myc protein.We demonstrate that, in all the tumor cell lines used, the MEK/ERK inhibitor U0126 rapidly induces c-Myc de-phosphorylation, which is followed by a marked reduction in its expression level, by inhibition of proliferation and by reversion of anchorage-independent growth. These data suggest that the targeting of pathways controlling c-Myc expression or stability reverses deregulated growth of different tumor-derived cell lines. Indeed, in RD cells, we found a marked down-regulation of cyclins E2, A and B and CDK2, all of which are known to be targets of c-Myc. Moreover, ectopic MadMyc chimera, a c-Myc function antagonist, causes dramatic growth arrest, CDK and cyclin modulation as well as inhibition of anchorage-independent growth in RD cells, as occurs in U0126-treated cells. In particular, we found that the mere inhibition of c-Myc by MadMyc chimera rescues the myogenic program, MHC expression and the acquisition of the myogenic-like phenotype in RD cells.Our data provide evidence of the key role played by the MEK/ERK pathway in the growth arrest and transformation phenotype of Rhabdomyosarcoma and of non muscle-derived tumor cell lines. In fact, MEK/ERK inhibitor, U0126, induces growth arrest, anchorage-dependent growth of these cell lines. In addition, the results of this study demonstrate that the direct inactivation of c-Myc by Mad/Myc chimera rescues myogenic program and leads to the reversal of the Rhabdomyosarcoma phenotype. In conclusion these data strongly suggest that the targeting of c-Myc by means of the MEK inhibitor can be tested as a promising strategy in anti-cancer therapy.