Refrakter pyoderma gangraenosum sikeres visilizumabkezelése colitis ulcerosás betegben = Pyoderma gangrenosum treated successfully with visilizumab in patients with ulcerative colitis

A pyoderma gangraenosum a legismertebb IBD-vel asszociált bőrbetegség, leggyakrabban az IBD aktív fázisában alakul ki. A visilizumab (Nuvion, PDL Bio Pharma, Amerikai Egyesült Államok) egy IgG2 típusú monoklonális antitest, amely a T-lymphocyták felszíni CD3 receptorának epszilon-láncához kötődik, csökkenti a perifériás vérben lévő nyugvó T-sejteken a CXCR-3-mediált kemotaxist, valamint az aktivált T-sejtek gyors apoptózisát idézi elő. Esetismertetés: a 40 éves férfi beteget az utóbbi közel 20 évben több mint 30 alkalommal kezelték bőrgyógyászaton ekzemának, illetve mycosisnak vélt alsó végtagi bőrelváltozások miatt. 1996 óta ismert colitis ulcerosája. Orális vagy szisztémás szteroidkezelésben 1997 óta részesül, amelynek az évek során számos szövődménye alakult ki. A pyoderma gangraenosum diagnózisát 2005-ben állították fel. 2006-ban a beteg egy gyógyszervizsgálatban vett részt, amelynek során két alkalommal 375 mcg visilizumabot kapott (5 mcg/ttkg) intravénásan. Hat hónappal a kezelés után a bőrelváltozások csaknem teljesen behámosodtak. Pyodermás bőrtünetek azóta sem jelentkeztek. Következtetés: az eset alapján felmerül, hogy a pyoderma gangraenosum etiológiájában kóros T-sejt-válasz játszhat szerepet. Súlyos colitis ulcerosa kezelésében a visilizumab nem váltotta be a hozzá fűzött reményeket, azonban a pyoderma gangraenosum esetében egy új terápiás lehetőséget jelenthet. | Pyoderma gangrenosum is a misleading designation for an idiopathic ulcerating cutaneous disease. The activity of pyoderma gangrenosum may or may not follow the activity of the inflammatory bowel disease. Visilizumab (Nuvion, PDL Bio Pharma, USA), a humanized IgG2 monoclonal antibody that binds to the human CD3 epsilon chain expressed on human T cells, induces the rapid production of selective chemokines, and reduces the CXCR3-mediated chemotaxis of the resting peripheral blood lymphocytes. In activated, but not resting T cells, visilizumab leads to rapid apoptosis. Case report: During a period of 20 years, a 40-year-old male took part in more than 30 courses of treatment for a dermatological condition misdiagnosed as crural eczema, mycosis and infected wounds. This ulcerative process was very severe in both crural regions. Ulcerative colitis was diagnosed a decade ago. He has been steroid-dependent since 1997. In 2005, pyoderma gangrenosum was diagnosed. In 2006, the patient participated in the visilizumab study and received 2x375 mcg study drug (5 mcg/kg/dose) intravenously. Six months after visilizumab administration, his leg ulcers healed. After the administration of visilizumab, pyoderma gangrenosum had not relapsed. Conclusion: In this severe pyoderma case, visilizumab also treated the skin disease. Although the colitis later worsened, the pyoderma gangrenosum has not recurred to date in this steroid-dependent patient. Pyoderma gangrenosum may be a T cell-mediated disease. The fact that biological therapy proved dramatically effective in this patient may suggest the use of these agents as first line of therapy in such cases

[1,5]-Hydride Shift-Cyclization versus C(sp2)-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines

Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp2)-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp3)-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp2)-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 uM IC50 value

Folyóirat-referátumok = From the literature

Alvászavarok: 1. M. Orth [et al.]: Alvásapnoe nôknél? – Az elfelejtett nem = Schlafapnoe bei Frauen? – Das vergessene Geshlecht Egészségmegőrzés: 1. R. H. Striegel-Moore [et al.]: Serdülő leányok üdítőital-fogyasztásának összefüggései: a nemzeti szív, tüdő és hematológiai intézet növekedésre és egészségi állapotra vonatkozó tanulmánya = Correlates of beverage intake in adolescent girls: The nation health, lung, and blood institute growth and health study 2. W. H. Dietz: Cukrozott italok, tejfogyasztás és a gyermekkori, ifjúkori elhízás = Sugar-sweetened beverages milk intake, and obesity in children and adolescents Gasztroenterológia: 1. T. A. Sentongo - V. Cohran - S. Korff [et al.]: A bél permeábilitásának változása és a Lactobacillus rhamnosuskezelés hatása rövidbél-szindrómás gyerekekben = Intestinal Permeability and Effects of Lactobacillus rhamnosus Therapy in Children with Short Bowel Syndrome Gyermekgyógyászat: 1. P. Lai [et al.]: Egy csecsemő kétfázisú stridorának szokatlan oka: suprasternalis bronchogén ciszta = An unusual case of biphasic stridor in an infant: suprasternal bronchogenic cyst Kardiológia: 1. T. Rowland - B. Fernhall: Cardiovascularis válaszok statikus terhelésre = Cardiovascular responses to static exercise: a reappraisa

Management of Peptic Ulcer Bleeding in Different Case Volume Workplaces: Results of a Nationwide Inquiry in Hungary

The aim of this study was to conduct a national survey to evaluate the recent endoscopic treatment and drug therapy of peptic ulcer bleeding (PUB) patients and to compare practices in high and low case volume Hungarian workplaces. A total of 62 gastroenterology units participated in the six-month study. A total of 3033 PUB cases and a mean of 8.15±3.9 PUB cases per month per unit were reported. In the 23 high case volume units (HCV), there was a mean of 12.9±5.4 PUB cases/month, whereas in the 39 low case volume units (LCV), a mean of 5.3±2.9 PUB cases/month were treated during the study period. In HCV units, endoscopic therapies for Forrest Ia, Ib, and IIa ulcers were significantly more often used than in LCV units (86% versus 68%; P=0.001). Among patients with stigmata of recent haemorrhage (Forrest I, II), bolus + continuous infusion PPI was given significantly more frequently in HCV than in LCV units (49.6% versus 33.2%; P=0.001). Mortality in HCV units was less than in LCV units (2.7% versus 4.3%; P=0.023). The penetration of evidence-based recommendations for PUB management is stronger in HCV units resulting lower mortality