tbuckley/cabot-search huggingface dataset:
Biopsy and non-invasive methods for the diagnosis of liver fibrosis: does it take two to tango?
Authors: L. Castera, M. Pinzani
Journal: Gut (2010)

The birth of Hepatology as a defined clinical discipline coincides with the introduction of Menghini's needle in the late 1950s.1 In those days, very little was known about the aetiology of liver disease and in the majority of patients diagnosis was mainly based on the morphological examination of liver specimens obtained with a biopsy. Features such as necrosis, inflammation and fibrosis were not precisely categorised, and the final label was merely descriptive—that is, chronic persistent, chronic active hepatitis and cirrhosis. In these terms, liver biopsy was the only available diagnostic means, and truly represented a gold standard. The introduction of the so-called ‘one second needle biopsy of the liver’ was characterised since the beginning by a significant cooperative effort between the clinician and the pathologist. Clinical hepatologists were trained in liver pathology and this led to the foundation of the main academic schools of Hepatology in Europe and the USA.

The introduction of scoring systems represented a step forward in the use of liver biopsy. This introduction implied the necessity for more precision in the evaluation of liver biopsy specimens that was beyond the description and, in many instances, the opinion of the pathologist. Overall, the introduction of scoring systems was supposed to facilitate the comparison between samples and the communication of the results according to a global agreement. However, this obvious advantage, once analysed by statistical studies, started to be criticised in term of reproducibility, intraobserver and interobserver agreement, etc. For these and other reasons (sampling error, lack of standards, etc.), the value of liver biopsy as gold standard started to become questionable for clinicians. These issues started to be quite evident when liver biopsy was used to assess the extent of disease progression in terms of fibrotic transformation of the liver tissue, and even more when the …
Increased Activity of Type I Regulatory Subunit of Cyclic Adenosine 3', 5'- Monophosphate-Dependent Protein Kinase in Estrogen- Induced Pituitary Tumors
Authors: G. Piroli, O. Pignataro, A. F. D. Nicola
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Previous studies have shown that binding of [ 3 H]cyclic adenosine 3‘, 5’- monophosphate(cAMP) is increased in cytosol of diethylstilbestrol (DES)- induced pituitary tumors. In tumor cells, the cAMP-binding proteins that stimulate cell proliferation have been shown to predominate over those that inhibit it. Purpose : This study was designed to determine the type of regulartory subunit(R) of cAMP- depentent protein kinase (PK) responsible for this binding by determining the type of subunit that is incerased in DES-induces pituitary tumors. Methods : Experiments were carried out on three groups of Fischer 344 rats: 1) rats with DES-induced pituitary tumors, 2) ovariectomized rats receiving short- term estrogen trestment with estradiol benzoate (E 2 ) for 4 days, and 3) ovariectomized control rats. We performed immunoprecipitation of RI and RII subunits with polyclonal antibodies in pituitary cytosol (direct method) or after separation of subunits by DEAE- cellulose chromatography (indirect method). The concentration of cAMP was also quantifeid by radioimmunoassay in pituitaries from the three gruoups. Results : Direct immunoprecipitation with RI antibody demonstrated a statistically signficant increase in [ 3 H]cAMP bound to RI in rats receiving E 2 for 4 days over that for control rats and an even more significant increase in rats with DES- induced pituitary tumors. There was little change in the nucleotide [ 3 ]HcAMP bound to RII. Immunoprecipitation of the eluted fractions after chromatography demonstrated an RI subunit in peaks 1 AND 2. whereas RII was contained almost exlusively in peak 2. After chromatography (indirect method), immunoprecipitation with RI and RII antibody indicated an overall increase in the level of binding to RI protein in tumors. Levels of cAMP in DES-induced pituitary tumors were also high compared with levels in controls or in glands from estrogen- treated rats. Conclusions : In DES- induced pituiary tumors, cAMP may be preferentially bound to one isozyme of PK, which supports current theories that cell proliferation and tumor growth correlate with high expression of the RI subunit. Impications : We plan studies to investigate the effects on tumor growth of the site-selective analogue 8-chloro-cAMP, which binds to RII and causes the elevated levels of the RI subunit of the tumor cells to return to normal levels. [J Natl Cancer Inst 84:1565–1571, 1992]
A national study on adherence to a basal cell carcinoma guideline; development of a tool to assess guideline adherence
Authors: R.J. Borgonjen, J.J.E. van Everdingen, C.A.F.M. Bruijnzeel-Koomen, P.C.M. van de Kerkhof, Ph.I. Spuls
Journal: British Journal of Dermatology (2014)

Clinical practice guideline implementation may be at variance with actual daily practice, as guideline adherence is a complex process depending on many actors and factors. Feedback regarding adherence is essential to monitor the effect that a guideline has in clinical practice and whether or not the quality of care is raised by implementation. Developing a tool for obtaining and giving nationwide feedback regarding adherence. From February 2010 to June 2013, a 32‐item questionnaire was used as an audit tool during committee visits to assess adherence across 37 dermatological centres in the Netherlands. The questions were derived from the recommendations by the Dutch Dermatological and Venereological Society (NVDV) in the Dutch Basal Cell Carcinoma (BCC) guideline. Five selected medical records per dermatologist were audited and the results were discussed with the audited centre. Data were pooled to calculate the compliance with each recommendation across all participating centres. Adherence to recommended actions varied considerably (20·2–100%) across the domains of prevention, diagnostics, treatments and aftercare. Using and reporting surgical margins, giving patient advice, restricting the use of cryosurgery for certain BCCs and reporting on prognostic factors all failed to reach a threshold of 80%. Nonadherence to recommended actions proved to be related to whether or not a dermatologist was directly involved. The findings emphasize the importance of direct feedback to practitioners regarding adherence. Furthermore, together with existing frameworks, the method described could be used by developers in a guideline update to identify and anticipate barriers to successful implementation.
Platelet Behaviour and Drugs Used in Cardiovascular Disease
Authors: J. R. Hampton, M. J. G. Harrison, A. J. Honour, J. R. A. Mitchell
Journal: Cardiovascular Research (1967)

A group of vasoactive drugs, commonly used in vascular disease, have been shown to affect human platelet behaviour. Glyceryl trinitrate, propranolol, tolazoline, phentolamine, and intensain inhibit platelet aggregation in vitro, and both in vitro and in vivo prevent adenosine diphosphate and noradrenaline from altering platelet electrophoretic mobility. The theoretical and practical implications are discussed.
Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience
Authors: U. De Giorgi, T. Demirer, H. Wandt, C. Taverna, W. Siegert, M. Bornhauser, T. Kozak, G. Papiani, M. Ballardini, G. Rosti
Journal: Annals of Oncology (2004)
Neurostimulation for Parkinson's Disease with Early Motor Complications
Authors: W.M.M. Schuepbach, J. Rau, K. Knudsen, J. Volkmann, P. Krack, L. Timmermann, T.D. Hälbig, H. Hesekamp, S.M. Navarro, N. Meier, D. Falk, M. Mehdorn, S. Paschen, M. Maarouf, M.T. Barbe, G.R. Fink, A. Kupsch, D. Gruber, G.-H. Schneider, E. Seigneuret, A. Kistner, P. Chaynes, F. Ory-Magne, C. Brefel Courbon, J. Vesper, A. Schnitzler, L. Wojtecki, J.-L. Houeto, B. Bataille, D. Maltête, P. Damier, S. Raoul, F. Sixel-Doering, D. Hellwig, A. Gharabaghi, R. Krüger, M.O. Pinsker, F. Amtage, J.-M. Régis, T. Witjas, S. Thobois, P. Mertens, M. Kloss, A. Hartmann, W.H. Oertel, B. Post, H. Speelman, Y. Agid, C. Schade-Brittinger, G. Deuschl
Journal: New England Journal of Medicine (2013)

Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease.In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia.For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group.Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).
Diabetes Incidence in 0- to 14-Year Age-Group in Italy
Authors: Flavia Carle, Rosaria Gesuita, Graziella Bruno, Giovanni V. Coppa, Alberto Falorni, Renata Lorini, Marco E. Martinucci, Paolo Pozzilli, Francesco Prisco, Marco Songini, Maria T. Tenconi, Valentino Cherubini
Journal: Diabetes Care (2004)

OBJECTIVE—The Registry for Type 1 Diabetes Mellitus in Italy (RIDI) Study Group was established to coordinate the registries of type 1 diabetes in Italy. This report is based on 3,606 children younger than 15 years diagnosed with type 1 diabetes and prospectively registered during 1990–1999 by nine centers, covering &amp;gt;35% of the Italian population. RESEARCH DESIGN AND METHODS—Registries were pooled in four geographic macro-areas: north, central, south, and insular. The completeness of registration was assessed by the capture-recapture method. Poisson regression analysis was used to evaluate temporal trend in incidence. RESULTS—Large variations in incidence were confirmed not only between Sardegna and the mainland but also among peninsular areas. In Sardegna, there was an excess of boys (the boy-to-girl incidence ratio was 1.4). The overall incidence showed average increases of 3.6% (P &amp;lt; 0.001) and 3.7% (P &amp;lt; 0.001) per year in peninsular Italy and in Sardegna, respectively. Significant increases in incidence rates were found in boys aged 10–14 years (6.7%, 95% CI 0.5–13.3) and in girls aged 5–9 years (6.6%, 0.5–13.1) living in the southern area. The incidence rate also increased in boys aged 10–14 years (5.0%, 0.3–10) and in girls aged 0–4 years (4.9%, 0.8–9.1) living in Sardegna. CONCLUSIONS—Italy is a country with large geographical variations in incidence rates of type 1 diabetes. However, the rates are evenly increasing both in the mainland and Sardegna, suggesting that similar environmental factors are operating over populations that have different genetic backgrounds.
The insulin ball
Authors: Terumasa Nagase, Yoshiya Katsura, Yoshiki Iwaki, Kenji Nemoto, Hidenori Sekine, Kazuhiro Miwa, Tsunao Oh-i, Keni Kou, Keiichi Iwaya, Masayuki Noritake, Takeshi Matsuoka
Journal: The Lancet (2009)
Adducin- and Ouabain-Related Gene Variants Predict the Antihypertensive Activity of Rostafuroxin, Part 2: Clinical Studies
Authors: Chiara Lanzani, Lorena Citterio, Nicola Glorioso, Paolo Manunta, Grazia Tripodi, Erika Salvi, Simona Delli Carpini, Mara Ferrandi, Elisabetta Messaggio, Jan A. Staessen, Daniele Cusi, Fabio Macciardi, Giuseppe Argiolas, Giovanni Valentini, Patrizia Ferrari, Giuseppe Bianchi
Journal: Science Translational Medicine (2010)

Five genetic variants that affect Na,K-ATPase interactions predict the blood pressure response to rostafuroxin but not to losartan and hydrochlorothiazide.
Loss of Integrin α1β1 Ameliorates Kras-Induced Lung Cancer
Authors: Ines Macias-Perez, Corina Borza, Xiwu Chen, Xuexian Yan, Raquel Ibanez, Glenda Mernaugh, Lynn M. Matrisian, Roy Zent, Ambra Pozzi
Journal: Cancer Research (2008)

Abstract The collagen IV binding receptor integrin α1β1 has been shown to regulate lung cancer due to its proangiogenic properties; however, it is unclear whether this receptor also plays a direct role in promoting primary lung tumors. To investigate this possibility, integrin α1-null mice were crossed with KrasLA2 mice that carry an oncogenic mutation of the Kras gene (G12D) and develop spontaneous primary tumors with features of non–small cell lung cancer. We provide evidence that KrasLA2/α1-null mice have a decreased incidence of primary lung tumors and longer survival compared with KrasLA2/α1 wild-type controls. Tumors from KrasLA2/α1-null mice were also smaller, less vascularized, and exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen and terminal deoxynucleotidyl-transferase–mediated dUTP nick-end staining, respectively. Moreover, tumors from the KrasLA2/α1-null mice showed diminished extracellular signal-regulated kinase (ERK) but enhanced p38 mitogen-activated protein kinase activation. Primary lung tumor epithelial cells isolated from KrasLA2/α1-null mice showed a significant decrease in anchorage-independent colony formation, collagen-mediated cell proliferation, ERK activation, and, most importantly, tumorigenicity when injected into nude mice compared with KrasLA2/α1 wild-type tumor cells. These results indicate that loss of the integrin α1 subunit decreases the incidence and growth of lung epithelial tumors initiated by oncogenic Kras, suggesting that both Kras and integrin α1β1 cooperate to drive the growth of non–small cell lung cancer in vivo. [Cancer Res 2008;68(15):6127–35]
Acute cholesterol reduction decreases leukocyte adhesiveness and improves peripheral microcirculatory function in patients with familial hypercholesterolemia
Authors: T. Sampletro, C. Palombo, G. Bigalli, M. Ferdeghini, A. Clardi, M. Kozàkovà, M. Taddei, M. Tuoni, A. Blonda
Journal: Journal of the American College of Cardiology (1998)
Associations of glutathione S‐transferase P1, M1, and environmental tobacco smoke with wheezing illness in school children
Authors: Y.‐L. Lee, Y.‐C. Lee, Y. L. Guo
Journal: Allergy (2007)

Background: Polymorphisms at the glutathione S‐transferase (GST) were associated with asthma‐related phenotypes. We hypothesized that the GSTP1 and GSTM1 genotypes could modify the effects of household environmental tobacco smoke (ETS) on childhood wheezing illness. Methods: We conducted a case‐control study comprised of 216 lifetime wheezing children and 185 nonwheezing controls, all of whom were selected from 2524 fourth‐ to ninth‐grade school children in southern Taiwan. Results: Homozygous GSTP1 Ile‐105 was significantly associated with current wheezing (OR = 1.78, 95% CI 1.04–3.12), but insignificantly associated with ever wheezing (OR = 1.26, 95% CI 0.82–1.94). The risks of ever or current wheezing on GSTM1 null genotype were positive but not statistically significant. Although household ETS exposure was not associated with wheezing illness, after excluding subjects having in utero ETS or active smoking habits, the adverse effects of household ETS exposure differed significantly by GSTP1‐105 genotypes. In children without any ETS exposure at home, GSTP1 Ile‐105 homozygosity was significantly related to increased risks for both ever wheezing (OR = 2.29, 95% CI 1.17–4.49) and current wheezing (OR = 4.86, 95% CI 1.86–12.70). In children with household ETS exposure, the risks of wheezing illness did not increase for those carrying two GSTP1 Ile‐105 alleles. Children carrying any GSTP1 Val‐105 allele were at a significantly greater risk of both ever and current wheezing when exposed to ETS, with a clear dose‐response relationship to the number of smokers at home. Conclusion: Household ETS exposure is a modifiable cause of wheezing illness in a genetically susceptible subpopulation.
Effect of the oral application of a highly selective MMP-13 inhibitor in three different animal models of rheumatoid arthritis
Authors: A. Jungel, C. Ospelt, M. Lesch, M. Thiel, T. Sunyer, O. Schorr, B. A. Michel, R. E. Gay, C. Kolling, C. Flory, S. Gay, M. Neidhart
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Introduction</h3> Chronic anal fissures (CAF) are frequently encountered in coloproctology clinics. Chemical sphincterotomy with pharmacological agents is recommended as first-line therapy. Topical nitrates (TN) are effective at healing CAF but recurrences are common. An alternative treatment modality is injection of botulinum toxin (BT) into the anal sphincter. We aimed to perform a systematic review and meta-analysis to compare the effectiveness of BT and TN in the management of CAF. <h3>Method</h3> The online published literature was searched for relevant articles from inception till January 2017. All published randomised trials (RCTs) that reported direct comparisons of BT and TN were included. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates. <h3>Results</h3> Five RCTs describing 313 patients (154 in BT, 159 in TN) were included. There was significant heterogeneity among the trials. On random effects analysis, there were no significant differences in incomplete fissure healing (OR=0.47, 95% CI=0.13 to 1.67, p=0.24) or recurrence (OR=0.61, 95% CI=0.26 to 1.43, p=0.26) between BT and TN, respectively. BT was associated with a higher rate of transcient anal incontinence (pooled OR=2.53, 95% CI=0.98 to 6.57, p=0.06) but significantly fewer side effects (OR=0.09, 95% CI=0.01 to 0.72, p=0.02) and headache (OR=0.10, 95% CI=0.01 to 0.77, p=0.03)) compared to TN. <h3>Conclusion</h3> BT is associated with fewer side effects when compared to TN but there is no difference in fissure healing. However, well-designed RCTs with adequate follow-up are needed to definitively answer this important clinical question. <h3>Disclosure of Interest</h3> None Declared
Using one-step nucleic acid amplification (OSNA) for intraoperative detection of lymph node metastasis in breast cancer patients avoids second surgery and accelerates initiation of adjuvant therapy
Authors: S. Klingler, F. Marchal, P. Rauch, O. Kenouchi, A.S. Chrétien, P. Genin, A. Leroux, J.L. Merlin
Journal: Annals of Oncology (2013)
DNA Damage–Induced Protein 14-3-3 σ Inhibits Protein Kinase B/Akt Activation and Suppresses Akt-Activated Cancer
Authors: Huiling Yang, Yu-Ye Wen, Ruiying Zhao, Yu-Li Lin, Keith Fournier, Heng-Yin Yang, Yun Qiu, Jose Diaz, Christine Laronga, Mong-Hong Lee
Journal: Cancer Research (2006)

Abstract 14-3-3 σ is induced by tumor suppressor protein p53 in response to DNA damage. p53 can directly transactivate the expression of 14-3-3 σ to cause a G2 cell cycle arrest when cell DNA is damaged. The expression of 14-3-3 σ protein is down-regulated in various tumors, but its function has not been fully established. Protein kinase B/Akt, a crucial regulator of oncogenic signal involved in cell survival and proliferation, is deregulated in many types of cancer. Akt activation can enhance p53 degradation, but its role in DNA damage response is not clear. Here, we show that Akt activation is diminished when p53 and 14-3-3 σ is up-regulated in response to DNA damage. Evidence is provided that 14-3-3 σ binds and inhibits Akt. In keeping with this concept, Akt-mediated cell survival is inhibited by 14-3-3 σ. Significantly, we show that 14-3-3 σ inhibits Akt-mediated cell growth, transformation, and tumorigenesis. Low expression of 14-3-3 σ in human primary breast cancers correlates with Akt activation. These data provide an insight into Akt regulation and rational cancer gene therapy by identifying 14-3-3 σ as a molecular regulator of Akt and as a potential anticancer agent for Akt-activated cancers. (Cancer Res 2006; (66)6: 3096-105)
Distinctive Features of Melanoma and Its Management in Elderly Patients
Authors: Dragos Ciocan, Coralie Barbe, Francois Aubin, Florence Granel-Brocard, Dan Lipsker, Michel Velten, Sophie Dalac, François Truchetet, Catherine Michel, Audrey Mitschler, Gwendoline Arnoult, Antoine Buemi, Stéphane Dalle, Philippe Bernard, Anne-Sophie Woronoff, Florent Grange
Journal: JAMA Dermatology (2013)

Life expectancy is increasing in most developed countries, and elderly people have the highest incidence of melanoma.To identify characteristics of melanoma and its management in the elderly compared with younger patients.Retrospective population-based study of incident cases of primary melanoma in 1621 patients with stage I or II melanoma in 2004 and 2008. Questionnaires administered to physicians and a survey of cancer registries and pathology laboratories were used to obtain data. The study was conducted in 5 regions in northeastern France.Characteristics of patients and tumors, circumstances of diagnosis, and further management in older patients (≥70 years, 487 patients [30.0%]) compared with younger ones (<70 years, 1134 [70.0%]).Older patients had more frequent melanomas of the head and neck (29.4% vs 8.7%; P < .001) and of the nodular, lentigo maligna, or acral lentiginous histologic subtypes. They had thicker and more frequently ulcerated tumors, categorized as T3 or T4 in 36.7% of cases vs 20.1% in younger patients. Diagnosis of melanoma occurred more frequently in a general practice setting and less frequently in direct consultation with a dermatologist or regular screening for skin cancer. Time to definitive excision was longer in older patients, and 16.8% of them compared with 5.0% of the younger population had insufficient excision margins (P < .001). A sentinel lymph node biopsy was performed in 23.3% of the older patients with melanoma thicker than 1 mm vs 41.4% in the younger patients (P < .001). Adjuvant therapy was less frequently started in older patients and was prematurely stopped in a higher proportion of that population.Age-related variations are observed at every step of melanoma management. The most important concerns are access of elderly people to settings for early diagnosis and excision with appropriate margins.