Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001.

PURPOSE: To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. RESULTS: Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05). CONCLUSION: There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.

Hepatitis G virus infection in primary Sjögren's syndrome: analysis in a series of 100 patients.

OBJECTIVE To determine the prevalence and clinical significance of hepatitis G virus (HGV) infection in a large cohort of patients with primary Sjögren¿s syndrome (SS). PATIENTS AND METHODS The study included 100 consecutive patients (92 female and eight male), with a mean age of 62 years (range 31¿80) that were prospectively visited in our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Two hundred volunteer blood donors were also studied. The presence of HGV-RNA was investigated in the serum of all patients and donors. Aditionally, HBsAg and antibodies to hepatitis C virus were determined. RESULTS Four patients (4%) and six volunteer blood donors (3%) presented HGV-RNA sequences in serum. HGV infection was associated with biochemical signs of liver involvement in two (50%) patients. When compared with primary SS patients without HGV infection, no significant differences were found in terms of clinical or immunological features. HCV coinfection occurs in one (25%) of the four patients with HGV infection. CONCLUSION The prevalence of HGV infection in patients with primary SS is low in the geographical area of the study and HCV coinfection is very uncommon. HGV infection alone does not seen to be an important cause of chronic liver injury in the patients with primary SS in this area.

[Phot. d'un noir albinos du Sénégal par J. Barbier, photographe à Dakar, Saint-Louis et Lyon, à l'occasion de l'exposition coloniale de Lyon, en 1894, don de C. Lacoste]

Donateur : Lacoste, C. (18..-19..?)

Bioavailability of repeated oral administration of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase in healthy volunteers.

BACKGROUND: MDL 100,240 (pyrido[2,1-a] [2]benzazepine-4-carboxylic acid,7-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-1,2,3,4,6,7,8, 12b-octahydro-6-oxo, [4S-[4alpha,7alpha(R(*)),12bbeta]]-) is a molecule possessing an inhibiting ability on both angiotensin converting enzyme (ACE) and neutral endopeptidase, the enzyme responsible for atrial natriuretic peptide (ANP) degradation. Such a dual mechanism of action presents a potential clinical interest for the treatment of hypertension and congestive heart failure. OBJECTIVES: To evaluate the bioavailability of MDL 100,240 and its accumulation over repeated oral administration, using ACE inhibition as a surrogate for plasma drug level and determining its profile after oral and i.v. administration. METHODS: First, in an open, one-period, single-dose study, the ACE inhibition profile was characterised following a 12.5 mg MDL 100,240 i.v. infusion. Second, in a three-group, parallel, randomised, double-blind study, each group of four subjects received q.d., over 8 days, 2.5, 10 or 20 mg of MDL 100,240 orally. The ACE inhibition profile was determined on day 1 and day 8. Trough plasma ACE was measured on days 2, 3 and 4. The recovery of ACE activity was monitored up to 72 h after the last dose of MDL 100,240. RESULTS: ACE inhibition profile was similar on day 1 and day 8, and trough inhibition remained unchanged after the 8 days of treatment with 10 mg or 20 mg. Following repeated 2.5-mg ingestion, trough inhibition increased from 33% to 44% after the eighth dose. The oral bioavailability of MDL 100,240 was estimated at 85%, not statistically different from 100%. The accumulation ratio at steady state was estimated at 112%. Expressing the accumulation ratio in terms of half-life, a t(1/2) of 0.31 days or 7. 5 h was estimated. CONCLUSION: MDL 100,240 (oral solution) has a good bioavailability, as estimated by ACE inhibition, and no drug accumulation seems to occur over 8 days with the 10-mg and 20-mg doses, but a slight rise in the trough level is observed with the 2. 5-mg dose.

Viscoelasticity in Achilles Tendonopathy: Quantitative Assessment by Using Real-time Shear-Wave Elastography.

Purpose To investigate the differences in viscoelastic properties between normal and pathologic Achilles tendons ( AT Achilles tendon s) by using real-time shear-wave elastography ( SWE shear-wave elastography ). Materials and Methods The institutional review board approved this study, and written informed consent was obtained from 25 symptomatic patients and 80 volunteers. One hundred eighty ultrasonographic (US) and SWE shear-wave elastography studies of AT Achilles tendon s without tendonopathy and 30 studies of the middle portion of the AT Achilles tendon in patients with tendonopathy were assessed prospectively. Each study included data sets acquired at B-mode US (tendon morphology and cross-sectional area) and SWE shear-wave elastography (axial and sagittal mean velocity and relative anisotropic coefficient) for two passively mobilized ankle positions. The presence of AT Achilles tendon tears at B-mode US and signal-void areas at SWE shear-wave elastography were noted. Results Significantly lower mean velocity was shown in tendons with tendonopathy than in normal tendons in the relaxed position at axial SWE shear-wave elastography (P < .001) and in the stretched position at sagittal (P < .001) and axial (P = .0026) SWE shear-wave elastography . Tendon softening was a sign of tendonopathy in relaxed AT Achilles tendon s when the mean velocity was less than or equal to 4.06 m · sec(-1) at axial SWE shear-wave elastography (sensitivity, 54.2%; 95% confidence interval [ CI confidence interval ]: 32.8, 74.4; specificity, 91.5%; 95% CI confidence interval : 86.3, 95.1) and less than or equal to 5.70 m · sec(-1) at sagittal SWE shear-wave elastography (sensitivity, 41.7%; 95% CI confidence interval : 22.1, 63.3; specificity, 81.8%; 95% CI confidence interval : 75.3, 87.2) and in stretched AT Achilles tendon s, when the mean velocity was less than or equal to 4.86 m · sec(-1) at axial SWE shear-wave elastography (sensitivity, 66.7%; 95% CI confidence interval : 44.7, 84.3; specificity, 75.6%; 95% CI confidence interval : 68.5, 81.7) and less than or equal to 14.58 m · sec(-1) at sagittal SWE shear-wave elastography (sensitivity, 58.3%; 95% CI confidence interval : 36.7, 77.9; specificity, 83.5%; 95% CI confidence interval : 77.2, 88.7). Anisotropic results were not significantly different between normal and pathologic AT Achilles tendon s. Six of six (100%) partial-thickness tears appeared as signal-void areas at SWE shear-wave elastography . Conclusion Whether the AT Achilles tendon was relaxed or stretched, SWE shear-wave elastography helped to confirm and quantify pathologic tendon softening in patients with tendonopathy in the midportion of the AT Achilles tendon and did not reveal modifications of viscoelastic anisotropy in the tendon. Tendon softening assessed by using SWE shear-wave elastography appeared to be highly specific, but sensitivity was relatively low. © RSNA, 2014.

Nanometer-scale oxidation of Si(100) surfaces by tapping mode atomic force microscopy

The nanometer¿scale oxidation of Si(100) surfaces in air is performed with an atomic force microscope working in tapping mode. Applying a positive voltage to the sample with respect to the tip, two kinds of modifications are induced on the sample: grown silicon oxide mounds less than 5 nm high and mounds higher than 10 nm (which are assumed to be gold depositions). The threshold voltage necessary to produce the modification is studied as a function of the average tip¿to¿sample distance.

La mania de les llistes: 100 biblioteques digitals i 'recol·lectors' de llibres electrònics

Selecció personal de 100 projectes de digitalització internacionals i locals actualment en funcionament. La tria s'ha fet seguint l'interès que poden tenir les obres incloses i en altres ocasions pels serveis, les eines i les aplicacions diferents que s'hi proposen. La major part dels recursos tenen com a objectiu oferir una còpia digital de llibres però també s'hi inclouen altres tipologies documentals: publicacions periòdiques, tesis, literatura grisa, fotografies, gravats, enregistraments sonors¿ Hi abunden els projectes fets per les biblioteques nacionals i universitàries, els projectes comercials més representatius i les col·leccions col·laboratives. Una tipologia a destacar és la de les plataformes que pretenen recuperar i difondre una cultura o una llengua. La llista inclou preferentment projectes de biblioteques digitals amb obres de domini públic, les obres de les quals es poden descarregar i imprimir; també hi són inclosos però materials de pagament. L'ordenació de la selecció està presentada alfabèticament.

La manía de las listas: 100 bibliotecas digitales y 'recolectores' de libros electrónicos

Selección personal de 100 proyectos de digitalización internacionales y locales actualmente en funcionamiento. La elección se ha hecho siguiendo el interés que pueden tener las obras incluidas y en otras ocasiones por los servicios, las herramientas y las aplicaciones diferentes que se proponen. La mayor parte de los recursos tienen como objetivo ofrecer una copia digital de libros pero también se incluyen otras tipologías documentales: publicaciones periódicas, tesis, literatura gris, fotografías, grabados, grabaciones sonoras... Abundan los proyectos realizados por las bibliotecas nacionales y universitarias, los proyectos comerciales más representativos y las colecciones colaborativas. Una tipología a destacar es la de las plataformas que pretenden recuperar y difundir una cultura o una lengua. La lista incluye preferentemente proyectos de bibliotecas digitales con obras de dominio público, las obras de las que se pueden descargar e imprimir, también están incluidos pero materiales de pago. La ordenación de la selección está presentada alfabéticamente.

Brevia de fide catholica (f. 1-52v). Acta paparum (f. 53-139v).

F. 1-52v. Recueil de textes de piété, en italien sauf le premier. « Confiteor Deo omnipotenti Patri et Filio et Spiritui sancto (...) martiribus tuis Grisanto et Darie, confessoribus tuis Prospero et Venerio atque beato Francisco... - ... eternam amen » (1). — [Rubrique :] « Quisti son li X comandam. de la leze ». « Primo non adorare altro che uno solo dio et per questo commandamento se veta le idole... - ... non e » (1v-3v). — [Rubrique :] « Quisti son li XII articoli de la fede ». « Credo in Dio padre omnipotente creatore del celo et de la terra. 1. S. Petro. Et in Yesu... - ... alli boni. 11. S. Thadeo. 12. S. Mathia » (3v). — [Rubrique :] « Quisti son li septe peccati mortali. Lo primo Elatio ». « Superbia cio e reputare de havere bene per propria virtu et non da Dio... - ... tante fiade pecca mortalmente » (3v-10). — [Rubriques :] « Quisti son li dexe comandamenti soto brevita » (...) « Quisti sono li septe sacramenti » (...) « Que son le VII opere de la misericordia temporale » (...) « Queste son le spirituale » (...) « Questi son li setti peccati mortali » (...) « Circha de sopra in li dexe comandamenti. Quista sun li V sentimenti de lo corpo » (...) « Quisti sono li septi doni del Spirito sancto che sono contra li VII peccati mortali » (...) « Queste sono le III virtu theologie » (...) « Quatuor sono le cardinale » (...) « Queste son le conditione de la confessione » (...) « Quisti son li casi de la papa sive papali » (...) « Casus exclusi » (...) « Quisti sun li cassi de lo episcopo sive episcopali » (...) (10-12). — [NICOLAUS DE AUXIMO, O. F. M. (Nicolò da Osimo), Compendio de salute], cf. Umberto Picciafuoco, Fr. Nicolò da Osimo: vita, opera, spiritualità, 1980 ; « Per dare breve introductione delle cose necessarie ad la salute ad ciaschuno simplice lo quale desidera de salvarse, me sono studiato de redirre le dicte cose sotto breve compendio, retracto de uno libro dicto Quadriga spirituale... - ... molto cose secondo li doctori » (12-52v).F. 53-139v. Actes pontificaux et varia. EUGENIUS IV papa, Bulla [ad Jacobum de Primadiciis de Bononia, O. F. M. (Giacomo Primadizzi) ?], de communione pascali, [07/07/1446], cf. Archivum Franciscanum Historicum, 21, 1928, p. 270 n. 1, 282-283 « Eugenius papa IIIIus. Dilecte fili salutem et apostolicam benedictionem. Fidedigna relatione percepimus in civitate Licii non parvam... - ... VIII kal. julii 1446, po. no. anno XVI° » (éd. ibid., p. 282-283, avec une date corrigée) (53-54). — [PAULUS II papa], Bulla, 14/04/1469 « I ». [Rubrique :] « Bulla que quotannis in cena Domini publicari per summum pontificem consuevit ». « Dilecti filii salutem et apostolicam benedictionem. Consueverunt predecessores nostri romani pontifices annis singulis in die cene Domini sedentes...-... die XIIII° aprilis 1469 p. n. anno quinto. L. Dathus » (55-56). — PAULUS II papa, Bulla, 30/03/1469 « 2. Bulla. Paulus (...). Consueverunt sancte memorie romani pontifices predecessoris [sic] nostri ad retinendam puritatem... - ... tertio kal. aprilis, p. n. anno quinto. De curia. Signata A. Ingherannus, L. Dathus » (56v-64). — PAULUS II papa, Bulla, 06/06/1469 « 3. Paulus (...). Decet romanum pontificem sic in suis fore gratiis liberalem quod in ecclesiarum... - ... octavo id. junii, p. n. anno quinto. De curia, B. Lunensis » (64v-67). — PAULUS II papa, Bulla, 02/07/1469 « Paulus papa II. 4. [Rubrique :] Presidenti monasteriorum Sancte Justine de Padua ». « Dilecte fili salutem et apostolicam benedictionem. Bullam presentibus alligatam constitutionis et decreti nostri circa annexa et juncta beneficia... - ... die IIa julii M° CCCC LXVIIII p. n. anno quinto. L. Dathus » (67v-68). — PAULUS II papa, Bulla, de casibus reservatis, [03/03/1470] cf. Cesare Censi, Manoscritti francescani della Biblioteca Nazionale di Napoli, 2 vol., 1971 (Spicilegium bonaventurianum, VII-VIII), t. I, p. 222, qui renvoie au ms. Napoli, Biblioteca Nazionale, V H 33 (n° 125 a de la liste de Cenci) ; incomplet de la fin « 5. [Rubrique :] Bulla pro casibus reservatis ». « Paulus (...). Etsi dominici gregis saluti semper intenti singulis cum humilitate poscentibus ea benigne... - ... omnipotentis Dei et beatorum » [Petri et Pauli...] (68v-70). — PAULUS II papa, Bulla, 23/11/1464 « 6. [Rubrique :] Contra symoniacos ». « Paulus (...). Cum detestabile scelus simoniace pravitates tam divinorum quam sacrorum canonum... - ... nono kal. decembres, p. n. anno primo » (70v-72). — PAULUS II papa, Bulla, [01/03/1468], cf. C. Censi, op. cit., ms. Napoli, Bibl. Naz., I H 43 et V H 33 (n° 50 ap et 125 d) « 7. [Rubrique :] Bulla prohibens ne bona ecclesiarum et Dei alienari possint ultra triennium ». « Paulus (...). Ambitiose perversorum cupiditati illorum precipue qui divinis et humanis legibus affectata... - ... M° CCCC LXVII kalendis martii p. n. anno quarto » (72v-74). — PAULUS II papa, Bulla, 31/01/1468 « 8. [Rubrique :] De celebratione dierum festorum in terris ecclesie ». « Paulus (...). Perniciosa consuetudo aut verius corruptela que in gravem divine majestatis ac sanctorum... - ... M° CCCC LXVII pridie kal. febr. anno p. n. IIII° » (74v-76v). — Exemplum de Raymundo cardinale nepote Honorii pape et beata Maria virgine et Annunciatione ejus. [Rubrique :] « Pro jejunio domine nostre ». « Honorius summus pontifex habuit ex sorore nepotem Raymundum nomine tituli sanctorum Johannis et Pauli cardinalem libidini ita deditum... - ... regna migravit » (77-79). — PAULUS II papa, Bulla, de jubilaeo, 19/04/1470 « 10 ( ?). [Rubrique :] De publicatione anni jubilei redacti ad M CCCC LXXV ». « Paulus (...). Ineffabilis providentia summi patris qui pro redemptione humani generis ejusque reconcilianda natura... - ... tertiodecimo kalendas maii p. n. anno sexto » (79-85). — PAULUS II papa, Breve, ad episcopum Cumanensem, 22/04/1471 « Breve pontificis ad episcopum Cumanensem. Paulus II. Venerabilis frater (...). Expositum fuit nobis nonnullos istius civitatis Cumane ejusque diocesis existere qui contra libertatem... - ... XXII aprilis 1471 p. n. anno septimo » (86-86v). — PAULUS II papa, Breve, ad episcopum Cumanensem, 07/06/1471 « Suprascriptum breve non habuit locum sed reformatum fuit in formam infrascriptam : Paulus II. Ven. (...). Expositum nobis fuit pro parte dilecti filii nobilis viri Galeaz Marie ducis Mediolani nonnullos istius civitatis Cumane... - ... 7° junii 1471 p. n. anno 7° » (86v-87v). — PAULUS II papa, Breve, [ad Galeazzum Mariam Sforza ducem Mediolanensem], 31/05/1471 « Dilecte fili (...). Diligenter exposuit nobis dilectus filius Augustinus de Rubeis eques et doctor Parmensis consiliarius et orator ad nos tuus... - ... ultimo maii 1471, p. n. anno septimo » (87v-88v). — NICODEMUS [TRANCHEDINI], Littera ad Galeazzum Mariam Sforza ducem Mediolanensem, 13/05/1471, cf. Paola Sverzelatti, « Per la biografia di Nicodemo Tranchedini [1413-1481] di Pontremoli, ambasciatore sforzesco », Aevum, 1998, LXII, 485-557 [4° Z 4794] « Littere Nicodemi ad illustrissimum d. ducem. El papa me ha dicto questa sera che heri sera deputo et immediate hebbe ad se li inferri... - ... Johachinus et Franciscus de Padua advocati consistoriales ». « Suprascriptis videnda commissa fuit bulla pontificis » (89-89v). — AUGUSTINUS DE RUBEIS (Agostino de’Rossi) et NICODEMUS [TRANCHEDINI], Littera ad Galeazzum Mariam Sforza ducem Mediolanensem, 25/05/1471 « Littere d. Augustini et Nicodemi ad principem. Illustrissimo (...). Questi xi sonno mo stati piu volte insieme et col papa anchora et heri se fece el consistorio... - ... XXV maii 1471. Augustinus et Nicodemus » (89v-91). — Iidem ad eumdem, 27/05/1471 « Eorundem. Illustrissimo (...). Credace la vestra signoria per cosa se havesse ad agitar. qua postquam questo nostro sancto patre fu facto papa... - ... XXVII maii 1471 » (91-94v). — [EUGENIUS IV papa, Gratiae concessae Francisco de Platea de Bononia, O. F. M., 01/1440], cf. Cesare Censi, Manoscritti francescani della Biblioteca Nazionale di Napoli, 2 vol., 1971 (Spicilegium bonaventurianum, VII-VIII), t. II, p. 1060, qui renvoie à deux exemplaires du texte, mss. Napoli, Biblioteca Nazionale, cod. VII G 50 et VII G 66 [n° 371 et 383 de la liste de Cenci] « Copia. Ego frater Franciscus de Bononia frater venerabilis viri fratris Jacobi de Primidiciis de Bononia Florentiam accessi... - ... M CCCC XL die III et die decima januarii » (95-98v). — PAULUS II papa, Breve ( ?), ad Julium Cesari de Varano domicellum, incomplet de la fin « Paulus episcopus (...) dilecto filio nobili viro Julio Cesari de Varano domicello civitatis nostre Camerini et pro nobis (...) gubernatori (...). Inter cura multiplices quibus assidue permimur illa precipue sollicitat mentem nostram... - ... merito commendari » (100-106v). — NICOLAUS V papa, Breve ( ?), ad Franciscum Sforza, 24/07/1447 « Nicolaus (...) dilecto filio nobili viro Francisco Sfortie vicecomiti, comiti et marchioni (...). Sedes apostolica pia mater recurrentibus ad eam cum humilitate filiis post excessum libenter... - ... nono kal. augusti, p. n. anno primo. Pe. de Noxeto » (107-111v). — FRANCISCUS PHILELPHUS ( ?), [De Sacerdotio Christi (extractum et translatum e graeco Souda), versio italica], cf. Giovanni Mercati, Ultimi contributi alla storia degli Umanistici, 1939, I, p. 74-76 (4° Z 1722 (90)) « Tractatello traducto per messere Francescho Philelpho singularissimo poetha de greco in latino per luy trovato presso autentici et antiqui autori, reducto in volgare ad contemplatione d’alcuni devoti cortesani del illustrissimo signiore duca di Milano, ad confirmatione de la fede nostra et confusione de Judei. Regnando Justiniano imperatore clementissimo fo uno homo principe de Judei chiamato Theodosio... - ... teneva occulto » (112-118v). — « Electi beneficii et superni doni data ad quella anima che oldira la sancta messa integramente monifestati per li sancti doctori... - ... ligno de la vita » (118v-119). — MARTINUS V papa, Bulla, de excommunicatione hereticorum, [28/03/1426 ?], incomplète de la fin ; cf. C. Censi, op. cit., I, p. 501-502 (n° 304 f) « 1. Excommunicationes plures contente in processu qui fit annuatim in curia in cena Domini. Martinus (...). Excommunicamus et anathematizamus ex parte omnipotentis Dei Patris et Filii et Spiritus sancti auctoritate Petri... - ... incursurum. Datum Rome etc » (120-122v). — « Item excommunicamus et anathematizamus omnes illos qui per se vel per alium vel alios directe vel indirecte... - ... cautione prestitis » (122v-123v). — PAULUS II papa, Bulla, 11/04/1471 « 2. Paulus (...). Consueverunt sancte memorie romani pontifices predecessores nostri ad retinendam puritatem... - ... tertio idus aprilis, p. n. anno VII° » (124-130v). — SIXTUS IV papa, Bulla, de excommunicatione hereticorum, 26/03/1472 « 2. Sixtus (...). Excommunicamus et anathematizamus ex parte omnipotentis Dei Patris et Filii et Spiritus sancti auctoritate quoque beatorum... - ... septimo kal. aprilis etc. anno primo » (131-134v). — SIXTUS IV papa, Breve ( ?), ad Ferdinandum I regem Sicilie, 01/03/1472 « 4. Sixtus (...) carissimo in Christo filio Ferdinando regi Sicilie illustri (...). Dum eximie fidelitatis devotionis atque prudentie tue ceterasque tibi a Domino traditas virtutes...-... kalendis martiis [sic] p. n. anno primo. M. Milinus » (135-139v).

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.

Gómez Santacruz, Julio: La Meseta Superior Hispana durante la Época Antonina. Universidad de Valladolid, 1993

El conocimiento de la Meseta Superior en la Antigüedad es muy desigual y obras como la presente, que sintetizan y reúnen aspectos dispersos en multitud de publicaciones, cubren un importante hueco. Por diversas causas la investigación venía atendiendo con mayor interés las etapas de cambio histórico, los pueblos prerromanos y los primeros tiempos de la implantación romana, la crisis del siglo III y su transformación posterior, etc. Se echaba en falta una obra monotemática sobre la maduración romanizadora, que indagara en los motivos de crisis que ya en ella se intuyen, durante ese siglo falsamente "anodino", es decir, el espacio de tiempo comprendido entre los años 96-198.

Canakinumab vs triamcinolone acetonide for treatment of acute flares and prevention of recurrent flares in "difficult to treat" gouty arthritis

Monosodium urate crystal deposition seen in gout stimulates IL-1 beta OR IL-1_; release. Canakinumab, a long-acting, fully human anti- IL-1 beta OR IL-1_; monoclonal antibody, effectively neutralizes IL-1 beta OR IL-1_;. Methods: This was an 8-week, dose-ranging, multi-center, blinded, doubledummy, active-controlled trial. Patients (aged 18-80 years) with an acute gout flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to one dose of canakinumab 10, 25, 50, 90, 150 mg s.c. or triamcinolone acetonide (TA) 40 mg i.m. Primary variable was assessed as pain intensity at 72 h post-dose (0-100 mm VAS). Secondary variables included pain intensity 24 and 48 h post-dose, time to 50% reduction in pain intensity, time to recurrence of gout flares up to 8 weeks post-dose, and rescue medication use. Results: 191/200 enrolled patients (canakinumab, n_143; TA, n_57) completed the study. Canakinumab showed significant dose-dependent pain reduction at 72 h. Canakinumab 150 mg showed superior pain relief versus TA starting from 24 h: estimated mean difference in pain intensity on VAS was -11.5 (24 h), -18.2 (48 h), and -19.2 (72 h) (all p_0.05). Canakinumab 150 mg provided a rapid onset of pain relief: median time to 50% reduction in pain was reached at 1 day with canakinumab 150 mg versus 2 days with TA (p_0.0006). At Week 8, recurrent flares occurred in 1 patient (3.7%) on canakinumab 150 mg versus 25 (44.6%) patients on TA (relative risk reduction, 94%; p_0.006). During 7 days post-dose, 6 patients (22.2%) on canakinumab 150 mg, and 31 patients (55.4%) on TA, took rescue medication. Time to first rescue medication was significantly longer with canakinumab 150 mg versus TA (hazard ratio, 0.36; p_0.02). Serious adverse events (canakinumab _lsqb_n_4_rsqb_ and TA _lsqb_n_1_rsqb_) were considered not treatment-related by investigators and no patient discontinued due to adverse events. Conclusions: Canakinumab 150 mg was well-tolerated, provided rapid and sustained pain relief in patients with acute gout flares, and significantly reduced the recurrent flare risk by 94% at 8-weeks post-dose compared with triamcinolone acetonide.