tbuckley/cabot-search huggingface dataset:
Prospective Multicenter Validation Confirms the Prognostic Superiority of the Endometrial Carcinoma Prognostic Index in International Federation of Gynecology and Obstetrics Stage 1 and 2 Endometrial Carcinoma
Authors: Jan P.A. Baak, Wim Snijders, Bianca van Diermen, Paul J. van Diest, Fred W. Diepenhorst, Jantine Benraadt
Journal: Journal of Clinical Oncology (2003)

To validate the prognostic value of the endometrial carcinoma prognostic index (ECPI; combined myometrium invasion, flow cytometric DNA ploidy, and morphometric mean shortest nuclear axis [MSNA]) versus classic prognosticators.Prospective multicenter ECPI analysis was conducted in 463 endometrial carcinomas with a median of 6.5 years (range, 1 to 10 years) follow-up, review of pathology features, and univariate (Kaplan-Meier) and multivariate (Cox) analyses.Initial routine and review diagnoses varied considerably (invasion depth, 11%; type, 20%; grade, 34%; vessel invasion, 72%); the review diagnoses were stronger prognostically. In International Federation of Gynecology and Obstetrics stage 1 (after histopathologic examination; pFIGO-1; n = 372; 38 deaths occurred as a result of disease [10.2%]), DNA ploidy was prognostic in hysterectomies (P <.00001) but not in curettages (P =.06). ECPI was a stronger prognostic indicator than other features. ECPI, MSNA, and DNA ploidy were also prognostic in pFIGO-1B and -1C subgroups. Multivariate analysis in pFIGO-1 showed that uterine MSNA < or = versus > 7.93 microm (hazard ratio [HR], 3.4) and grade (as 1 + 2 v 3; HR, 2.6) added to the ECPI (HR, 32), but only in patients with an unfavorable ECPI of > 0.87. Adjuvant radiotherapy was not an independent prognostic factor in any of the subgroups. In pFIGO-2 (n = 46), ECPI, DNA-ploidy, and age (< or = 64, > 64 years) were significant. In FIGO-3 (n = 31) and FIGO-4 (n = 14), none of the classic or other features analyzed was of prognostic value, which explains why in previous studies using different mixtures of FIGO stages, DNA ploidy prognostic results varied.In endometrial carcinoma, DNA-ploidy is prognostic in hysterectomy and not in curettage samples. The ECPI is prognostically much stronger than the classic features widely used for therapy triage in pFIGO-1 and -2.
International prevalence of recurrent wheezing during the first year of life: variability, treatment patterns and use of health resources
Authors: J. Mallol, L. Garcia-Marcos, D. Sole, P. Brand
Journal: Thorax (2010)

Kupffer cells protect liver from bacterial infections. In the current study, we compared <i>Mycobacterium tuberculosis</i> (M.tb) growth and cytokine production by mice kupffer cells and alveolar macrophages. M.tb H37Rv infected kupffer cells and alveolar macrophages produced equal amounts of TNF-α, IL-6, IL-10 &amp; IL-1β. In contrast, kupffer cells restricted M.tb growth better than alveolar macrophages (1 ± 0.346×10<sup>6</sup> CFU vs. 4 ± 0.916×10<sup>6</sup> CFU, p&lt;0.03). There is no significant difference in the apoptosis of M.tb infected kupffer cells and alveolar macrophages. In contrast, M.tb infected kupffer cells expressed significant higher amounts of autophagy molecules LC-3B, ATG-7, ATG-5 and Beclin-1 (p&lt;0.005, p&lt;0.002, p&lt;0.0032 &amp; p&lt;0.004 respectively) compared to M.tb infected alveolar macrophages as determined by real-time PCR. This was confirmed by Western blot and confocal microscopy. Our results suggest autophagy is involved in better restriction of M.tb growth by kupffer cells. Prime PCR analysis for 35 intracelluar signaling molecules those are involved in autophagy as well as in cytoskeleton indicated that M.tb infected kupffer cells significantly express higher levels of VASP (Vasodilator-stimulated phosphoprotein), RhoA (Ras homolog gene family member A) and Arp3 (Actin–related protein 3) genes (two fold, p&lt;0.01, p&lt;0.02&amp;p&lt;0.02 respectively) compared to M.tb infected alveolar macrophages. Studies are underway 1. To confirm whether autophagy is involved in better restriction of M.tb growth in kupffer cells. 2. Determine the role of cytoskeleton proteins those are involved in enhanced autophagy and M.tb growth inhibition in kupffer cells. 3. Determining <i>in vivo</i> relevance to our current findings using mouse model of M.tb infection.
G-CSF influences mouse skeletal muscle development and regeneration by stimulating myoblast proliferation
Authors: Mie Hara, Shinsuke Yuasa, Kenichiro Shimoji, Takeshi Onizuka, Nozomi Hayashiji, Yohei Ohno, Takahide Arai, Fumiyuki Hattori, Ruri Kaneda, Kensuke Kimura, Shinji Makino, Motoaki Sano, Keiichi Fukuda
Journal: The Journal of Experimental Medicine (2011)

After skeletal muscle injury, neutrophils, monocytes, and macrophages infiltrate the damaged area; this is followed by rapid proliferation of myoblasts derived from muscle stem cells (also called satellite cells). Although it is known that inflammation triggers skeletal muscle regeneration, the underlying molecular mechanisms remain incompletely understood. In this study, we show that granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) is expressed in developing somites. G-CSFR and G-CSF were expressed in myoblasts of mouse embryos during the midgestational stage but not in mature myocytes. Furthermore, G-CSFR was specifically but transiently expressed in regenerating myocytes present in injured adult mouse skeletal muscle. Neutralization of endogenous G-CSF with a blocking antibody impaired the regeneration process, whereas exogenous G-CSF supported muscle regeneration by promoting the proliferation of regenerating myoblasts. Furthermore, muscle regeneration was markedly impaired in G-CSFR–knockout mice. These findings indicate that G-CSF is crucial for skeletal myocyte development and regeneration and demonstrate the importance of inflammation-mediated induction of muscle regeneration.
1202 SEQUENCE ANALYSIS OF HCV VARIANTS FROM A PHASE IIA TRIAL OF MIRAVIRSEN (MIR), AN OLIGONUCLEOTIDE TARGETING MIR-122, IN TREATMENT NAIVE PATIENTS WITH CHRONIC HCV INFECTION
Authors: A.K. Patick, A. Chen, L.J. van Doorn, E. van der Veer, K. Zeh, A.K. Raney, M.R. Hodges
Journal: Journal of Hepatology (2012)
Induction of Thyroid Cancer Cell Apoptosis by a Novel Nuclear Factor κB Inhibitor, Dehydroxymethylepoxyquinomicin
Authors: Dmitriy V. Starenki, Hiroyuki Namba, Vladimir A. Saenko, Akira Ohtsuru, Shigeto Maeda, Kazuo Umezawa, Shunichi Yamashita
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The objective of the study was to determine the effects of a novel selective nuclear factor κB (NF-κB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in thyroid carcinoma cells in vitro and in vivo and to additionally elucidate the molecular mechanisms underlying the action of this chemotherapeutic agent. Experimental Design: In the in vitro experiments, the induction of apoptosis by DHMEQ in various human thyroid carcinoma cell types was determined by flow cytometry analysis of annexin-V binding and the caspase activation by Western blotting. For the in vivo study, female nu/nu mice were xenografted with s.c. FRO thyroid tumors. DHMEQ solution was injected i.p. at a dose of 8 mg/kg/day for two weeks. Tumor dimensions were monitored twice weekly, and apoptosis in tumor specimens was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. Results: Treatment with DHMEQ substantially inhibited the translocation of p65 and p50 NF-κB subunits to the nucleus, the DNA-binding activity of the RelA/p65, NF-κB-dependent expression of the inhibitor of apoptosis (IAP)-family proteins, cIAP-1, cIAP-2, and XIAP, and the de novo synthesis of inhibitor of nuclear factor κB α. At concentration levels ranging from 0.1 to 5 μg/ml, DHMEQ induced a caspase-mediated apoptotic response that could be abrogated by the c-Jun NH2-terminal kinase inhibitor SP600125 but not by either mitogen-activated protein/extracellular signal-regulated kinase kinase or p38 inhibitors. In contrast, normal human thyrocytes were resistant to DHMEQ-induced apoptosis. At higher doses of DHMEQ we observed the necrotic-like killing of both normal and malignant thyrocytes, which was resistant to mitogen-activated protein kinase inhibitors. In nude mice DHMEQ substantially inhibited tumor growth without observable side effects, and increased numbers of apoptotic cells were observed in the histologic sections of tumors treated with DHMEQ. Conclusions: Our results show the potential usefulness of the novel NF-κB inhibitor, DHMEQ, in future therapeutic strategies for the treatment of thyroid cancers that do not respond to conventional approaches.
HYPERNEPHROMA OF THE OVARY
Authors: A. K. Gordon
Journal: BMJ (1920)

<h3>Objectives</h3> To identify current ‘gaps’ in clinical practice or therapeutic knowledge of the care of neonatal neurointensive care patients and to determine the impact healthcare technologies can have on improving outcomes. <h3>Design</h3> The Cambridge Institute for Manufacturing’s (IfM) roadmapping methodology. <h3>Setting</h3> Cambridge, UK. <h3>Participants</h3> 16 delegates were selected through professional networks. They provided coverage of academia and clinical skills, as well as expertise in neonatology, engineering and technology development. <h3>Main outcome measures</h3> A ‘strategic landscape’ has been developed with ‘landmarks’ identified as ‘trends or drivers’, ‘patient pathway experience and unmet needs’ and ‘enabling project or resources’. Priorities were voted on by delegates. <h3>Results</h3> 26 strategic ‘landmarks’ were identified, and of these 8 were considered ‘trends or drivers’, 8 ‘patient pathway experience and unmet needs’ and 10 as ‘enabling project or resources’. Of these, five priorities for the future of neonatal neurocritical care were identified by a voting process: real-time video monitoring for parents; individualised management of preterm infants in neonatal neurocritical care based on real-time multimodal monitoring; continuous electroencephalogram monitoring for early seizure diagnosis; neuroprotection: understanding basic mechanisms; and sleep measurement. <h3>Conclusions</h3> Through the use of the IfM methodology, a list of priorities has been developed for future work into improving the experience and possible outcomes of newborn infants with brain injuries and their families. While not an exhaustive list, it provides the beginning for a national conversation on the topic.
Zosteriform lentiginous naevus with ipsilateral rigid cavus foot
Authors: MARTIN PORT, JAMES COURNIOTES, MARK PODWAL
Journal: British Journal of Dermatology (1978)

A patient is presented with a rigid cavus deformity associated with a painful linear keratotic lesion on the lateral plantar border. A unilateral zosteriform lentiginous naevus is found on the same side as the foot deformity. Electrodiagnostic evaluation suggests the presence of a non-specific neuromuscular process on the affected side. This association has not previously been reported.
Effect of Apheresis of Low-Density Lipoprotein on Peripheral Vascular Disease in Hypercholesterolemic Patients with Coronary Artery Disease
Authors: Abraham A. Kroon
Journal: Annals of Internal Medicine (1996)

Background: Apheresis of low-density lipoprotein (LDL) is an effective lipid-lowering treatment in hypercholesterolemic patients who have coronary artery disease and are refractory to drugs. More aggressive lipid-lowering therapy may further slow the progression of atherosclerosis. Objective: To compare the effect of LDL apheresis and simvastatin therapy with the effect of simvastatin therapy alone on the progression of peripheral vascular disease. Design: Open, randomized, single-center study. Setting: University hospital. Patients: 42 men with primary hypercholesterolemia (total cholesterol level > 8.0 mmol/L) and extensive coronary atherosclerosis. Intervention: Biweekly apheresis of LDL plus simvastatin, 40 mg/d (n = 21), or simvastatin, 40 mg/d (n = 21), for 2 years. Measurements: Lipid and lipoprotein levels, changes in hemodynamically significant stenoses in the aortotibial tract (measured by ankle:arm systolic blood pressure ratio combined with Doppler spectrum analysis of the femoral artery), and changes in the mean intima-media thickness of three carotid artery segments. Results: Mean baseline LDL cholesterol levels decreased from 7.8 to 3.0 mmol/L in the apheresis and simvastatin group and from 7.9 to 4.1 mmol/L in the simvastatin-only group; mean lipoprotein(a) levels decreased from 57.0 to 44.5 mg/dL (change, −19%)in the former group and increased from 38.4 to 44.5 mg/dL (change, 15%) in the latter group. In the apheresis group, the number of patients with hemodynamically significant stenoses in the aortotibial tract decreased from 9 to 7; in the simvastatin-only group, the number increased from 6 to 13 (P = 0.002). Mean intima-media thickness decreased by a mean ±SD of 0.05 ± 0.34 mm in the apheresis group and increased by 0.06 ± 0.38 mm in the simvastatin-only group (P < 0.001). According to multiple regression analysis, changes in apolipoprotein B, total cholesterol, and lipoprotein(a) levels accounted for changes in the aortotibial tract (R2 = 0.36); changes in lipoprotein(a) and apolipoprotein A1 levels accounted for changes in the intima-media thickness of the carotid artery (R2 = 0.49). Conclusions: Aggressive lipid lowering with simvastatin and LDL apheresis decreased the intima-media thickness of the carotid artery and prevented an increase in the number of hemodynamically significant stenoses in the lower limbs. Therapy with simvastatin alone did not prevent progression of carotid or aortotibial vascular disease.
Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research
Authors: C Salliot, D van der Heijde
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To perform a systematic literature review of the long-term safety of methotrexate (MTX) monotherapy in rheumatoid arthritis (RA). <h3>Methods:</h3> A search was performed in Medline, Cochrane and EMBASE. Adults with RA who had received MTX monotherapy for more than 2 years were studied. <h3>Results:</h3> 88 published studies were included. Over 12 years of treatment, the termination rate of MTX due to toxicity was less than for sulfasalazine, gold, d-penicillamine and higher than for hydroxychloroquine (level of evidence 2a–2b). Long-term use of MTX does not appear to be a risk factor for serious infections, including herpes zoster (2b–4), and could provide a survival benefit by reducing cardiovascular mortality (2b). The prevalence of raised liver enzymes (more than twice the upper limit of normal) is close to 13% of patients; 3.7% of patients stopped MTX permanently owing to liver toxicity (2b). Data on the risk for liver fibrosis/cirrhosis are conflicting: a meta-analysis showed an incidence of fibrosis of 2.7% after 4 years of MTX (2a). However, two other studies on sequential liver biopsies did not show evidence for developing severe damage (2b). Insufficient data are available to fully assess the risk of lymphoma and malignancies, although there is no strong evidence of increased risk (2b–4). <h3>Conclusion:</h3> This systematic literature search on MTX monotherapy with relatively low-dose use during at least 2 years shows favourable long-term safety.
Higher Mortality After Allogeneic Peripheral-Blood Transplantation Compared With Bone Marrow in Children and Adolescents: The Histocompatibility and Alternate Stem Cell Source Working Committee of the International Bone Marrow Transplant Registry
Authors: Mary Eapen, Mary M. Horowitz, John P. Klein, Richard E. Champlin, Fausto R. Loberiza, Olle Ringdén, John E. Wagner
Journal: Journal of Clinical Oncology (2004)

Peripheral-blood stem cells (PBSC) may be used as an alternative to bone marrow (BM) for allogeneic transplantation. Despite lack of data on PBSC transplantation in children, there has been a change in clinical practice, with increasing numbers of children receiving PBSC allografts.We compared the results of 143 PBSC and 630 BM transplants from human leukocyte antigen-identical sibling donors in children aged 8 to 20 years with acute leukemia. PBSC transplant recipients were older, and were more likely to have advanced leukemia, receive growth factors post-transplantation, and have undergone transplantation more recently. Risks of acute and chronic graft-versus-host disease (GVHD), treatment-related mortality, relapse, treatment failure (relapse or death), and overall mortality were compared using Cox proportional hazards regression to adjust for potentially confounding factors.Hematopoietic recovery was faster after PBSC transplantation. Risks of grade 2 to 4 acute GVHD were similar, but chronic GVHD risk was higher after PBSC transplantation (relative risk [RR], 1.85; 95% CI, 1.28 to 2.66; P = .001). In contrast to reports in adults, treatment-related mortality (RR, 1.89; 95% CI, 1.28 to 2.80; P = .001), treatment failure (RR, 1.31; 95% CI, 1.03 to 1.68; P = .03), and mortality (RR, 1.38; 95% CI, 1.07 to 1.79; P = .01) were higher after PBSC transplantation. Risks of relapse were similar.These data suggest poorer outcomes after PBSC compared with BM transplantation in children after adjusting for relevant risk factors. Given the trend toward increased use of PBSC allografts in children, prospective clinical trials are required to determine their appropriate role in this group of patients.
Post-irradiation surgery for bronchogenic carcinoma
Authors: L. Smith, T. Parnsingha
Journal: Thorax (1969)

In an attempt to improve both the resectability and survival rates for bronchogenic carcinoma, pre-operative supervoltage radiotherapy was introduced in 1961 and continued for a period of three years. Patients with either a histological or cytological diagnosis were given a tumour dose of 4,500 r over six weeks and then a two-month period elapsed before surgery. A follow-up of cases treated during the period revealed a five-year survival rate of 15·7%. This rate is low when compared with the results achieved at this hospital with surgery alone. This finding is attributed to the harmful effects of radiotherapy which have led to a high bronchopleural fistula rate of 15·5%. A single case of myocardial radionecrosis also occurred. No improvement is noted in the resectability rate. An overall assessment is that radiotherapy has provided no benefits but has in fact greatly increased both the morbidity and mortality rates.
Genotype differences in susceptibility and resistance development of hepatitis C virus to protease inhibitors telaprevir (VX-950) and danoprevir (ITMN-191)
Authors: Ingrid Imhof, Peter Simmonds
Journal: Hepatology (2011)

Protease inhibitors (PIs) have proven to be effective adjuncts to interferon/ribavirin treatment of hepatitis C virus (HCV) infections. Little clinical or in vitro data exists, however, on their effectiveness for nontype 1 genotypes that predominate in Europe, the Middle East, Africa, and most of Asia. NS3 protease and NS4A genes from genotypes 1-6 were inserted into the JFH clone to generate replication-competent intergenotype chimeras. Susceptibility to PIs was determined by replication and infectivity assays. To study resistance development, chimeras were cultured in subinhibitory concentrations of PIs and mutations phenotypically characterized. Marked differences in susceptibility of different genotypes to danoprevir (ITMN-191) and telaprevir (VX-950) were observed. Genotypes 1, 4, and 6 showed median inhibitory concentration (IC50) values of 2-3 nM, &gt;100-fold lower than genotypes 2/3/5 (250-750 nM). Telaprevir susceptibilities varied over a 4-fold range, with genotypes 1 and 2 being most susceptible and genotypes 4 and 5 most resistant. Culture of genotypes 1-6 in PIs induced numerous mutations in the NS3 protease domain, highly variable between genotypes. Introduction of danoprevir and BILN 2061-induced mutations into the original clones by site-directed mutagenesis (n = 29) all conferred resistant phenotypes, with particularly large increases (1-2 log greater IC50 values) in the initially susceptible genotypes 1/4/6. Most introduced mutations and showed little or no effect on replicative fitness. Conclusion: Major differences were found between genotypes in their susceptibility and resistance development to PIs. However, equal sensitivities of genotypes 1, 4, and 6 to danoprevir and a broader efficacy range of telaprevir between genotypes than initially conceptualized provide strong evidence that PIs might be effectively used beyond their genotype 1 target group. (HEPATOLOGY 2011;)
Assessing the Association of Pioglitazone Use and Bladder Cancer Through Drug Adverse Event Reporting
Authors: Carlo Piccinni, Domenico Motola, Giulio Marchesini, Elisabetta Poluzzi
Journal: Diabetes Care (2011)

To analyze the association between pioglitazone use and bladder cancer through a spontaneous adverse event reporting system for medications.Case/noncase bladder cancer reports associated with antidiabetic drug use were retrieved from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) between 2004 and 2009 and analyzed by the reporting odds ratio (ROR).Ninety-three reports of bladder cancer were retrieved, corresponding to 138 drug-reaction pairs (pioglitazone, 31; insulin, 29; metformin, 25; glimepiride, 13; exenatide, 8; others, 22). ROR was indicative of a definite risk for pioglitazone (4.30 [95% CI 2.82-6.52]), and a much weaker risk for gliclazide and acarbose, with very few cases being treated with these two drugs (6 and 4, respectively).In agreement with preclinical and clinical studies, AERS analysis is consistent with an association between pioglitazone and bladder cancer. This issue needs constant epidemiologic surveillance and urgent definition by more specific studies.
Intervertebral discitis presenting as oligoarthritis
Authors: A T Marshall
Journal: Annals of the Rheumatic Diseases (2004)

The symptoms of intervertebral discitis may be indistinct, making diagnosis difficult. The onset may be acute or insidious, and radicular or spinal compressive symptoms and signs may be present. Purulent infection may spread to surrounding soft tissues, and epidural abscess formation is recognised. Long term neurological sequelae may result, and mortality of between 7% and 18% has been reported.1,2 Vigilance is required if the diagnosis is to be made early, and treatment should be of adequate duration to reduce the rate of recurrent infection. To our knowledge, this is the first report of a case of intervertebral discitis in a patient presenting with an oligoarthritis.

A 62 year old woman was referred with a 2 week history of oligoarthritis and fever. She had developed acute back pain with fever 12 hours after visiting a spa in Italy. On returning home, her back symptoms resolved, but she developed persistent fever with pain and swelling of both knees, left ankle, and left hip. There was no significant past medical history. On examination, her temperature was 39°C. She had a full range of spinal movements and no spinal tenderness, but had synovitis of both knees, left hip, and left ankle. Her throat was hyperaemic. Examination was otherwise unremarkable. …