U radu se istražuju prve prionske bolesti od kojih je većina genetskog podrijetla. Uključuju točkaste mutacije (promjena jedno baznog para, change in a single base pair Adenine/Guanine, ...Thymin/Cytosine) DNA, insercija oktapeptida u N-ti dio prionskog proteina (3 do 216 oktapeptida), delecije (samo dva ili tri su poznata do sada). Tri ili više insercija potrebna za ovu bolest. To je 35 točkastih mutacija (najčešće su na kodonima 102, 178 i 200). Najnovija varijanta CJB, koja nastaje konzumacijom mesa zaraženog goveda, karakterizira polimorfizam Metionin/Metionon (M/M) na kodonu 129 u 98 posto slučajeva. U ostalih oblika prionske bolesti nema zabilježenih promjena u prionskom genomu. Točkaste mutacije karakterizira jedna promjena u jednom baznom paru od 109 postojećih u ljudskom genomu. Genetske prionske bolesti čine 10-15 posto svih slučajeva prionske bolesti. Ne-genetske prionske bolesti čine 85-90 posto slučajeva, a zajedno se javljaju u 1,5-2,5 slučaja na milijun stanovnika. Genetske prionske bolesti su istovremeno i infektivne. Patološki prionski protein (PrPSc) potreban je za postavljanje dijagnoze. Klinička dijagnoza genetskih i ne-genetskih prionskih bolesti čini se vrlo kompliciranom. U bolesnika s genetskim prionskim bolestima ponekad postoje anamnestički podaci o sličnim slučajevima koji su se pojavili u ovoj ili prijašnjim generacijama. Genetske prionske bolesti mogu se dijagnosticirati analizom baznih parova laboratorijskom metodom ili automatskim uređajem ili citokemijom, metodom lančane reakcije polimerazom, Western blot metodom, imunoenzimskim testom (ELISA). Za izvođenje ovih metoda potrebno je konstruirati tzv. „primere“ ili početnice za kodone 102, 178 i 200. Rade se i obdukcije, biopsije, elektroneurodijagnostika i analiza cerebrospinalnih markera prionskih bolesti. Diferencijalna dijagnostika na druge bolesti je također vrlo važna. Najviše publikacija objavio je Prusiner, koji je dobio i Nobelovu nagradu. On je nedavno promijenio svoje mišljenje o eliminaciji proteina X i prihvatio tezu o utjecaju stranih čimbenika. Patološki prionski protein PrPSc ne može nastati iz prionskog proteina PrPC jer PrPSc, kao protein, ne može stvarati nove proteine. PrPSc je proizvod gena, što znači da je nukleoprotein. U radu smo sažeto prikazali njegove ideje o genetskim prionskim bolestima. Infektivnost genetskih i ne-genetskih prionskih bolesti čini se vrlo niska. U posljednjih 40 godina analizirana je kultura tkiva: mnogo puta je bila pozitivna i uzročnik je mogao proći “pasaže”. Godine 2007. objavljen je rad o virusnoj etiologiji prionskih bolesti. Međutim, mnogi sojevi otkriveni do danas mogli su se uspoređivati samo elektronskim mikroskopiranjem. Pronađene su čestice veličine 20 do 50 nanometra, koje su se smatrale virusima, ali usporedba nije bila moguća. Nekoliko drugih neurotropnih virusa također je detektirano, čime se zakomplicirala dijagnostika prionskog uzročnika. Potrebna su daljnja istraživanja kulture tkiva, što je razvidno iz brojne do sada objavljene literature.
Bovina spongiformna encefalopatija (BSE) je prionska bolest goveda, koja se pojavila 1985. godine u Velikoj Britaniji i izazvala veliku epidemiju izrokovanu hranom. Oboljelo je više od milijun ...životinja. Bolest se širila izvozom britanskih prehrambenih proizvoda za goveda (mesno i koštano brašno), najviše u europske zemlje, zatim Kanadu, Sjedinjene Američke Države i Japan. BSE je prenosiva na ljude konzumacijom inficiranog mesa; više od 160 slućajeva ove »varijante« Creutzfeldt-Jacobove bolesti je bila potvrđena u Velikoj Britaniji, 26 u Francuskoj i rijetki slučajevi u drugim zemljama. Konatalna infekcija u potomaka inficiranih goveda se javlja u nekih 10 %. Mlijeko je od ogromne važnosti u ljudskoj prehrani, osobito djece, a infektivnost mlijeka u ovom času još nije sasvim jasna, i premda je malo vjerojatna, ipak najnovija istraživanja pokazuju, da je moguća u određenim uvjetima, i stoga su potrebna dalja istraživanja, te epidemiološke mjere za izolaciju mogućih rizičnih životinja. Za jednu drugu sličnu prionsku bolest, a to je scrapie, infektivnost mlijeka je dokazana. Situacija na svjetskom tržištu mlijeka je danas kaotična i zahtijevala bi usku suradnju odgovornih političara i ekonomista, uz stručni nadzor veterinara i liječnika u svijetu i u Hrvatskoj.
Iatrogenic diseases are disorders caused by the treatment of physician or surgeon (iatros from Greek "healer"). The disease develops by transmission of prion-infected material from the (clinically ...inapparent) donor to the recipient. First case significantly confirmed by animal bioassay was described in a corneal transplant 1974 and another following a neurosurgical procedure in 1977. Over one hundred of cases were detected in recipients of cadaveric, prion infected pituitary hormones (mostly growth hormone or, significantly less, gonadotrophins); the majority in France, UK and USA. Over one hundred of cases were detected following transplantation of prion-infected dura mater (mostly lyophilized commercial preparations) mostly in Japan. Some hormonal as well dura mater cases still occur because of an enormously prolonged incubation period. There are no fresh cases because cadaveric hormones were replaced by synthetic preparations and cadaveric dura mater by autologous tissue (fascia lata, fascia temporalis). Actual problems of iatrogenic prion infections are confined to surgery/neurosurgery, ophthalmology, otorhinolaryngology and dental surgery. Prions have also been detected outside the central nervous system, posterior eye, peripheral nerves, muscles, spleen, lymphoreticular system as tonsils and appendix, intestine, urine (?), olfactory cilia and central olfactory pathway representing a route of infection (nasal secretions). General anaesthesia may also be involved. Medical devices in contact with infected tissues became contaminated within minutes. Iatrogenic infections may occur thereafter incubating for years or decades. They are difficult to register because the hospital documentation has been actually kept for ten years only. It is evident that prion diseases have frequently a surgical history, according to some authors in one third of patients. Another problem of greatest importance is the prion decontamination of infected medical devices that is really difficult at present and rarely, if ever, properly performed in greatest majority of world hospitals. The decontamination methods will be presented in the second part of this article.
We have by now methods for the safe decontamination of medical devices. They include (a) NaOH, preferably combined with autoclaving in a simultaneous process at 121-134 C (b) NaOCl, alone at ambient ...temperature for some delicate instruments or combined with autoclaving (but separately); (c) autoclaving alone at 134 C for 18 minutes (Consensus in most European countries); (d) chemical decontamination using alkaline detergents (pH 11-12), proteases (properase, proteinase K, pronase or others) in combination with SDS for temperature-sensitive instruments, i.e. endoscopes and (e) combination of chemicals with autoclaving for temperature-resistant devices. The way of instruments from the operation room to the department of sterilisation (decontamination) is of considerable importance to avoid dessication and fixation of proteins onto instrument surfaces. For these purpose polypropylene pans willed with 0.1N NaOH or appropriate chemicals are very useful for immersion of devices immediately after being used-and then, after transport, transferred into the autoclave using the same fluid, with some fluid added, if necessary for instruments to be immersed. Temperature-sensitive devices in pans with chemicals must not be autoclaved but treated as proposed by the chemicals producer-at ambient or low temperature. In any case devices must not be cleaned in automated washers if not previously decontaminated. The empty pans must finally be autoclaved at 134 C 18 minutes as well.
A new calculation using off-shell matrix elements with TMD parton densities supplemented with a newly developed initial state TMD parton shower is described. The calculation is based on the
KaTie
...package for an automated calculation of the partonic process in high-energy factorization, making use of TMD parton densities implemented in TMDlib. The partonic events are stored in an LHE file, similar to the conventional LHE files, but now containing the transverse momenta of the initial partons. The LHE files are read in by the
Cascade
package for the full TMD parton shower, final state shower and hadronization from
Pythia
where events in HEPMC format are produced. We have determined a full set of TMD parton densities and developed an initial state TMD parton shower, including all flavors following the TMD distribution. As an example of application we have calculated the azimuthal de-correlation of high
p
t
dijets as measured at the LHC and found very good agreement with the measurement when including initial state TMD parton showers together with conventional final state parton showers and hadronization.
The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many ...established and emerging applications.
The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many ...established and emerging applications.
Introduction
Cardiac arrest is the major cause of sudden death in developed countries. Extracorporeal cardiopulmonary resuscitation (ECPR) employs extracorporeal membrane oxygenation (ECMO) in ...patients without return of spontaneous circulation (ROSC) by conventional cardiopulmonary resuscitation (CPR). Aim of the current study was to assess short- and long-term outcome in patients treated with ECPR in our tertiary center and to identify predictors of outcome.
Methods
We retrospectively collected data of all patients treated with ECPR at our institution from 2002 to 2013. Outcome was assessed according to patient records; good neurological outcome was defined as cerebral performance category 1 or 2. Quality of life data was collected using EQ-5 questionnaire. Uni- and multivariate analysis was applied to identify predictors of outcome.
Results
One-hundred and seventeen patients were included into the study. Weaning from ECMO was successful in 61 (52 %) patients. Thirty-day survival endpoint was achieved by 27 (23 %) patients. Good neurological outcome was present in 17 (15 %) patients. Multivariate analysis revealed baseline serum lactate as the strongest predictor of outcome, whereas age and out-of-hospital CPR did not predict outcome. The optimal lactate cut-off to discriminate outcome was determined at 4.6 mmol/l HR 3.55 (2.29–5.49),
p
< 0.001, log-rank test.
Conclusion
ECPR represents a treatment option in patients without ROSC after conventional CPR rescuing 15 % of patients with good neurological outcome. Serum lactate may play a crucial role in patient selection for ECPR.