tbuckley/cabot-search huggingface dataset:
Neuropathy in Non-Freezing Cold Injury (Trench Foot)
Authors: Michael S Irwin, Roy Sanders, Colin J Green, Giorgio Terenghi
Journal: Journal of the Royal Society of Medicine (1997)

Non-freezing cold injury (trench foot) is characterized, in severe cases, by peripheral nerve damage and tissue necrosis. Controversy exists regarding the susceptibility of nerve fibre populations to injury as well as the mechanism of injury. Clinical and histological studies (n=2) were conducted in a 40-year-old man with severe non-freezing cold injury in both feet. Clinical sensory tests, including two-point discrimination and pressure, vibration and thermal thresholds, indicated damage to large and small diameter nerves. On immunohistochemical assessment, terminal cutaneous nerve fibres within the plantar skin stained much less than in a normal control whereas staining to von Willebrand factor pointed to increased vascularity in all areas. The results indicate that all nerve populations (myelinated and unmyelinated) were damaged, possibly in a cycle of ischaemia and reperfusion.
Natural selection on the gag, pol, and env genes of human immunodeficiency virus 1 (HIV-1).
Authors: S A Seibert, C Y Howell, M K Hughes, A L Hughes
Journal: Molecular Biology and Evolution (1995)

Natural selection on polymorphic protein-coding loci of human immunodeficiency virus-1 (HIV-1), the more geographically widespread of the two viruses causing human acquired immune deficiency syndrome (AIDS), was studied by estimating the rates of nucleotide substitution per site in comparisons among alleles classified in families of related alleles on the basis of a phylogenetic analysis. In the case of gag, pol, and gp41, the rate of synonymous substitution generally exceeded that of nonsynonymous substitution, indicating that these genes are subject to purifying selection. However, in the case of several of the variable (V) regions of the gp120 gene, especially V2 and V3, comparisons within and between families often showed a significantly higher rate of nonsynonymous than of synonymous nucleotide substitution. This pattern of nucleotide substitution indicates that positive Darwinian selection has acted to diversify these regions at the amino acid level. The V regions have been identified as probable epitopes for antibody recognition; therefore, avoidance of such recognition seems likely to be the basis for positive selection on these regions. By contrast, regions of HIV-1 proteins identified as epitopes for T cell recognition show no evidence of positive selection and are often highly conserved at the amino acid level. These results suggest that selection favoring avoidance of T cell recognition has not been a major factor in the history of HIV-1 and thus that avoidance of T cell recognition is not likely to be a major factor in the pathogenesis of AIDS.
临床证据（六）儿童心跳呼吸停止
Authors: 王槿芳
Journal: BMJ (2001)

背景知识定义 非溺水性医院外儿童心跳呼吸停止是指发生在医疗机构之外的无脉搏和无呼吸的状态 ,而且不是由于溺水引起的。婴儿猝死综合征这一术语是指突然的、意想不到的儿童死亡 ,通常发生于 1个月至 1岁 ,死后全面检查不能找出确切死亡原因1。近似婴儿猝死综合征患儿是指发生意想不到的、病因不明的心跳呼吸停止后存活的儿童。发病率 /患病率 11项研究报告了非溺水性医院外儿童心跳呼吸停止的发病率 (表 1) 2 12 。这其中 3项研究是前瞻性的 ,其他研究是回顾性的2 9。 9项研究报告了整个人群的发病率 (包括成人及儿童 ) 2 8,10 ,11,7项研究报告了儿童人群的发病率2 ,3,6
Residual mass in lymphoma may not be residual disease.
Authors: G P Canellos
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.6.931 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3373263 Residual mass in lymphoma may not be residual disease. G P CanellosxG P CanellosSearch for articles by this author https://doi.org/10.1200/JCO.1988.6.6.931 First Page PDF © 1988 by American Society of Clinical Oncology
WP744, an novel anthracycline highly active against wild-type and doxorubicin-resistant bladder cancer cell lines
Authors: Sangkyou Lee, Izabela Fokt, H. Barton Grossman, Bogdan Czerniak, Colin Dinney, Waldemar Priebe
Journal: Cancer Research (2005)

2389   The lack of availability of effective drugs and acquired drug resistance are two significant problems in the treatment of bladder cancer. WP744 is a novel DNA binder that is structurally related to doxorubicin (DOX) and highly apoptotic and active against multidrug-resistant tumors of several types. We tested WP744 activity against a panel of sensitive and DOX-resistant human bladder cancer cell lines. WP744 showed 3 to 5 times the cytotoxicity of DOX against human bladder cancer cell lines UM-UC-6, UM-UC-2, UM-UC-3, and UM-UC-14. WP744 was still more cytotoxic (78-fold greater than DOX) and an effective inducer of apoptosis in the DOX-resistant variant UM-UC-6dox. WP744-induced cell growth inhibition and apoptosis seem to result from cell cycle arrest at G2/M phase. The uptake of WP744 was much faster than DOX in the both sensitive and resistant cell lines (UM-UC-6 and UM-UC-6dox). The cellular localization of WP744 was similar to that of DOX, but the nuclear concentrations of WP744 were much higher than those of DOX. We conclude that WP744 is a potent cytotoxin and inducer of apoptosis in human bladder cancer cells and can overcome resistance to DOX. These results warrant further evaluation in in vivo tumor models. This work was supported, in part, The University of Texas Genitourinary Cancer SPORE Grant (Grant NO. P50 CA91846), and by the Grant from the Welch Foundation.
Management of adverse skin reactions to anticancer agents: The Gustave Roussy Institute experience
Authors: D. Giacchero, C. Mateus, F. Frigui, J. P. Arnault, L. Maksimovic, B. Thuillier, A. Celebic, A. Auperin, B. Escudier, C. Robert
Journal: Journal of Clinical Oncology (2009)

e20638 Background: Anticancer therapies are associated with various and multiple cutaneous side effects frequently impacting patients’ quality of life and sometimes impairing treatment continuation. Some new skin syndromes and their potential relationship with drug efficacy have been the subject of hundreds of publications over the last few years. Methods: All physicians in our institution were informed by mail about the creation of a weekly consultation and the availability of an emergency call number specifically devoted to the management of adverse cutaneous reactions to anticancer agents. Patients could be referred to us from our institute or from other french institutes. All cutaneous side effects were recorded. Type, severity, and duration of symptoms were described. Imputability of the drugs was evaluated according to semiological, chronological and bibliographical criteria. Results: Over a 4 months period, 215 visits have been performed for a total of 128 patients. 169 events were reported among which 123 were considered to be imputable to the drugs. Several new cutaneous side effects were identified. Hiring a beautician and a pedicure for aesthetic complaints or hand foot skin reactions has been necessary in several cases. Causative agents were mostly targeted therapies (76.4%). Topical (n=132) or systemic treatments (n=45) were prescribed. Temporary dose reduction or treatment interruption was recommended in 18 cases (10.6%). This pilot experience was highly appreciated by both patients and physicians. It was consolidated as a permanent organization at the frontier between oncology and dermatology with the creation of an adapted case report form (CRF). Conclusions: There is a real need for dermatological management of skin side effects in a cancer institute, especially if early trials testing new agents are performed. Dedicated collaboration between oncologists and dermatologists should be promoted as well as the creation of a global skin-oriented CRF in order to facilitate international collaborations and to evaluate the impact of this dermatological management on compliance to treatment. No significant financial relationships to disclose.
India sees progress in child health but rising obesity, shows health survey
Authors: Sophie Cousins
Journal: BMJ (2016)

Some states in India have made great strides in improving maternal and child health over the past decade, the fourth National Family Health Survey has found.

The findings of the first phase of the survey for 2015-16, which covered 13 states and two union territories, also showed vast improvements in immunisation coverage and some improvement in nutrition among children.1

The survey found that states including Andhra Pradesh, Bihar, Goa, and West Bengal had infant mortality rates of fewer than 51 deaths per 1000 live births. This is an improvement compared with the last survey in …
Patient participation in clinical decision-making for treatment of T3 laryngeal cancer: a comparison of state and process utilities.
Authors: J van der Donk, P C Levendag, A J Kuijpers, F H Roest, J D Habbema, C A Meeuwis, P I Schmitz
Journal: Journal of Clinical Oncology (1995)

PURPOSE To study the use of two different approaches, and feasibility of four commonly used utility assessment methods to assess preferences for treatment of T3-laryngeal cancer by surgery or radiation therapy (RT). METHODS Utility assessment methods, namely, time trade-off (TTO), standard reference gamble (SRG), rating scale (RS), and direct comparison (DC), were used to assess utilities in two groups of former cancer patients (n = 10 for both), a group of clinicians (n = 9), and a group from the general population (n = 10). For the treatment modalities, ie, surgery and RT, two types of scenarios were developed and used: the state scenario, which describes a stable health state after treatment, and the process scenario, which describes a dynamic process. First, utilities were assessed based on state scenarios. Next, respondents were thoroughly informed and educated with respect to the relevant aspects of both treatment modalities. Subsequently, utilities were again assessed, but now based on the process scenarios. The outcome of each approach was calculated and expressed in a quality-adjusted life-expectancy (QALE) score for each treatment modality, and the treatment with the highest outcome was said to be the preferred treatment modality. RESULTS In general, a higher QALE score for each treatment modality was found for clinicians and for the general population as compared with the former-cancer-patient groups. When the outcome of both approaches was compared on an individual level dependent on the utility assessment method, 32% to 43% of respondents showed an inconsistent treatment preference. CONCLUSION The approach to assess utilities and the extent to which respondents are informed about treatment modalities have a major effect on individual treatment preferences.
Histologic Variation Among Poorly Differentiated Invasive Carcinomas of the Human Uterine Cervix2
Authors: N. Auersperg, H. Erber, A. Worth
Journal: JNCI Journal of the National Cancer Institute (1973)

Patterns of growth and invasion were correlated with ultrastructural evidence of squamous, basal, or glandular differentiation in 17 cervical carcinomas classified as poorly differentiated by histopathologic criteria. Traits of the spinous stage of differentiation (e.g., tonofibrils, glycogen, desmosomes) were retained predominantly by tumors that grew as compact, expanding masses, showed central necrosis, and elicited leukocytic responses, whereas traits of basal or glandular differentiation (e.g., basement membranes, secretory activlty) were retained predominantly by carcinomas characterized by diffuse invasion, extensive associations with connective tissues, and vascularization. Only 1 carcinoma lacked all ultrastructural evidence of differentiation, while spinous and glandular characteristics coexisted in cells of some tumors. Secretory activity, deposition of extracellular materials, and the accumulation of cortical cytofilaments by cancer cells at the interface with connective tissues seemed to be interrelated processes and possibly associated with invasiveness. Fibrillar nuclear inclusions werefound in 13 tumors. The results indicate that traits of differentiation, retained to a fragmentary degree not immediately obvious histologically, may greatly influence the growth pattern of apparently undifferentiated carcinomas and that definite correlations exist between some common histopathologic characteristics of these tumors and specific retained normal cell properties.
Smoking and mortality--beyond established causes.
Authors: Claudio Pedone, Raffaele Antonelli Incalzi
Journal: New England Journal of Medicine (2015)

To the Editor: The longitudinal cohort study by Carter et al. (Feb. 12 issue)(1) provides evidence of new causes of death associated with smoking. We were surprised by the authors' statement that among the deaths that were associated with smoking, a small proportion was due to other, less plausibly causal, associations with outcomes, such as suicide and accidents. The tables in the Supplementary Appendix of the article (available at NEJM.org) show that for current smokers who were 55 years of age or older, the relative risk of death was 4.4 from suicide and 1.6 from accidents among women and 3.2. . . Language: en
Secondary Tumors Arising in Patients Undergoing BRAF Inhibitor Therapy Exhibit Increased BRAF–CRAF Heterodimerization
Authors: Lise Boussemart, Isabelle Girault, Hélène Malka-Mahieu, Christine Mateus, Emilie Routier, Margot Rubington, Nyam Kamsu-Kom, Marina Thomas, Gorana Tomasic, Sandrine Agoussi, Marie Breckler, Mélanie Laporte, Ludovic Lacroix, Alexander M. Eggermont, Andrea Cavalcanti, Florent Grange, Julien Adam, Stéphan Vagner, Caroline Robert
Journal: Cancer Research (2016)

BRAF inhibitors (BRAFi) elicit therapeutic responses in metastatic melanoma, but alarmingly, also induce the formation of secondary benign and malignant skin tumors. Here, we report the emergence and molecular characterization of 73 skin and extracutaneous tumors in 31 patients who underwent BRAFi therapy. The majority of patients presented with classic epidermal tumors such as verrucous papillomas, keratoacanthomas, and squamous cell carcinomas (SCC). However, 15 patients exhibited new or rapidly progressing tumors distinct from these classic subtypes, such as lymph node metastasis, new melanomas, and genital and oral mucosal SCCs. Genotyping of the tumors revealed that oncogenic RAS mutations were found in 58% of the evaluable tumor samples (38/66) and 49% of the control tumors from patients not treated with BRAFi (30/62). Notably, proximity ligation assays demonstrated that BRAF-CRAF heterodimerization was increased in fixed tumor samples from BRAFi-treated patients compared with untreated patients. Our findings reveal that BRAF-CRAF complex formation is significantly associated with BRAFi treatment, and may therefore serve as a useful biomarker of BRAFi-induced cutaneous and extracutaneous tumor formation.
Paclitaxel, cisplatin, and cyclophosphamide (PCC) first-line chemotherapy for advanced ovarian carcinoma: Long-term results of a phase II study
Authors: A. García-Velasco, S. Hernando, C. Mendiola, D. Castellano, A. Sánchez-Muñoz, O. Del Val, L. Manso, M. Quintela, H. Cortés-Funes
Journal: Journal of Clinical Oncology (2004)

5135 Background: Despite high responses to cisplatin-based combination chemotherapy, the overall survival rate for advanced ovarian cancer remains poor. The combination of PCC as 1st-line treatment for ovarian cancer (OC) has significant activity with high primary response rates. To evaluate long-term results and to assess prognostic factors which have an impact on overall survival we analysed the data from a prospective phase II trial of this treatment combination Methods: 54 patients with OC ( FIGO IIc n=9, IIIc the n=38, IV n=7) were treated between January 1997 and December 2000 with six cycles of P (175mg/m2), C (75mg/m2) and C (600mg/m2) after optimal (n=22) or suboptimal (n=32) debulking surgery. Median age at treatment was 52 years. Tumour histology was adenocarcinoma in all cases (34 of endometrioid subtype, 6 clear cells, and 4 undifferentiated). CA 125 was elevated after surgery in 44 patients and at the end of chemotherapy in 6 patients. A second laparotomy was performed after chemotherapy to 14 patients with macroscopic disease Results: Of 30 evaluable patients for response, 15 achieved a clinical complete response (50%), 12 a partial response (40%), and 3 disease stabilization (10%). With a median follow-up of 56 months (range: 28–153), 26 patients remain alive (49%) and 15 free of recurrence (28%). Median progression-free survival (PFS) was 19 months, and median overall survival (OS) 46 months. 5 years rates of PFS and OS were 26% and 43% respectively. OS rate for FIGO IIIc-IV patients was 35%. In a multivariate analysis, the only negative prognostic factors for survival were: FIGO stage IIIc-IV (p<0.04), suboptimal debulking surgery (p<0.001), and elevated CA 125 at the end of chemotherapy (p<0.05) Conclusions: Our study confirms the effectiveness of PCC regimen in the treatment of epithelial OC in the long term. FIGO stage, extend of debulking surgery, and CA 125 at the end of chemotherapy, are independent prognostic factors for overall survival. These long-term results support the conduct of randomised studies to determine the impact of this triplet in the treatment of advanced ovarian cancer No significant financial relationships to disclose.
Context-specific interactions between Notch and ALK1 cannot explain ALK1-associated arteriovenous malformations
Authors: Elizabeth R. Rochon, Daniel S. Wright, Max M. Schubert, Beth L. Roman
Journal: Cardiovascular Research (2015)

Notch and activin receptor-like kinase 1 (ALK1) have been implicated in arterial specification, angiogenic tip/stalk cell differentiation, and development of arteriovenous malformations (AVMs), and ALK1 can cooperate with Notch to up-regulate expression of Notch target genes in cultured endothelial cells. These findings suggest that Notch and ALK1 might collaboratively program arterial identity and prevent AVMs. We therefore sought to investigate the interaction between Notch and Alk1 signalling in the developing vertebrate vasculature.We modulated Notch and Alk1 activities in zebrafish embryos and examined effects on Notch target gene expression and vascular morphology. Although Alk1 is not necessary for expression of Notch target genes in arterial endothelium, loss of Notch signalling unmasks a role for Alk1 in supporting hey2 and ephrinb2a expression in the dorsal aorta. In contrast, Notch and Alk1 play opposing roles in hey2 expression in cranial arteries and dll4 expression in all arterial endothelium, with Notch inducing and Alk1 repressing these genes. Although alk1 loss increases expression of dll4, AVMs in alk1 mutants could neither be phenocopied by Notch activation nor rescued by Dll4/Notch inhibition.Control of Notch targets in arterial endothelium is context-dependent, with gene-specific and region-specific requirements for Notch and Alk1. Alk1 is not required for arterial identity, and perturbations in Notch signalling cannot account for alk1 mutant-associated AVMs. These data suggest that AVMs associated with ALK1 mutation are not caused by defective arterial specification or altered Notch signalling.
Upregulated expression of interleukin-33 and alternative activation of macrophages in a model of an acute exacerbation of asthma
Authors: Rakesh Kumar, Melissa Scott, Rylie Keogh, Cristan Herbert, Jessica Siegle, Nicodemus Tedla
Journal: European Respiratory Journal (2011)

The role of alveolar macrophages (AM) in the pathogenesis of an acute exacerbation of asthma is poorly understood. In a clinically relevant mouse model, we have shown that AM are activated to secrete pro-inflammatory cytokines, and that these activated AM can stimulate primed CD4+ T cells to secrete Th2 cytokines (Am J Pathol 2010; 177:1657). We sought to further characterise the nature of these activated macrophages and the mechanism of activation. Female BALB/c mice were systemically sensitised to ovalbumin (OVA) and received chronic low-level challenge with aerosolised OVA for 4 weeks. Following this, mice received a single moderate-level challenge to induce airway inflammation simulating an acute exacerbation. AM and tissues were collected 4 hours later. Control groups included naive animals, and mice that only received either chronic challenge or a single moderate-level challenge. AM from an acute exacerbation exhibited significantly enhanced expression of markers of alternative activation, including mRNA for arginase-1, FIZZ1, Ym1 and eotaxin-2. These AM also exhibited elevated expression of cell surface proteins associated with antigen presentation to T cells, including CD86 and MHC class II. In parallel, expression of mRNA for IL-33 in the airway wall was strikingly increased, with evidence of enhanced immunoreactivity for IL-33 in the cytoplasm of airway epithelial cells and plasma cells within the airway wall. Collectively, these data imply an important role for alternatively activated AM in the pathogenesis of an acute exacerbation of asthma, and suggest that IL-33 may contribute to the activation of these cells.
Cochlear Implants in Children: Principles, Practice and Predictions
Authors: Gerard M O'Donoghue
Journal: Journal of the Royal Society of Medicine (1996)

An audit was undertaken of the first 36 children who had received cochlear implants in Nottingham. These children had previously derived no benefit from prolonged trials of powerful hearing aids. Following implantation, all children could hear warble tones at all audiometric frequencies from 500 to 4000 Hz at sound pressure levels between 30 and 50 dB. The majority of children implanted below the age of 5 years developed intelligible spoken language after 3 years. The outcomes for children born deaf and those who acquired deafness under the age of 3 years were substantially similar. The best results were obtained in those children who were implanted before the age of 5 years or in whom the deafness was of short duration. The needs of implanted children continue over many years. A small number of dedicated, well-funded multidisciplinary teams are needed to meet the growing demand nationally.
Abnormalities in Na+/H+ antiporter activity in diabetic nephropathy.
Authors: L L Ng, J E Davies
Journal: Journal of the American Society of Nephrology (1992)

In hypertensive humans and the spontaneously hypertensive rat, increased cellular Na+/H+ antiport activity has been demonstrated in leukocytes, platelets, skeletal muscle, and vascular smooth muscle cells. This membrane abnormality may be associated with medial thickening of resistance vessels. A similar membrane transport abnormality has also been demonstrated in leukocytes and fibroblasts from type 1 diabetic patients with nephropathy. This membrane transport marker of hypertension may indicate a predisposition to essential hypertension in such patients and may lead to diabetic nephropathy, possibly from mesangial expansion.