Diss.--Philosophische Fakultät--Hamburg, 1967. / Bibliogr. p. 182-189. Index.

Abstract not available

Texte remanié de: Th. Etat--Tours, 2004. / Bibliogr. p. 273-298.

Diss.--Tübingen--Eberhard-Karls-Univ., 2007. / Sources et bibliogr. p. 443-475.

<p> Dicobalt octacarbonyl reacts with a wide variety of molecules containing trichloromethyl functionalities to yield carbynyl tricobalt nonacarbonyl clusters of the general formula R-CCo 3 (CO) 9 . While these clusters have been shown to undergo many reactions, mechanistic studies on these systems are sparse. In particular, their rather facile decarbonylation processes are not well understood. </p> <p> Complexes of the type Ar-CO-CCo 3 (CO)9 readily lose CO to produce the corresponding Ar-CCo 3 (C0) 9 clusters but the origin of the carbon monoxide extruded was not known . Speculation had focussed on two possibilities: firstly, direct elimination of the ketonic carbonyl - perhaps via radical intermediates - and, secondly, via initial loss of a cobalt carbonyl ligand (to produce a 16-electron cobalt vertex) with subsequent migration of the original ketonic group onto the coordinatively unsaturated cobalt center. These two mechanistic possibilities are differentiable by labelling either the cobalt carbonyl sites or the ketonic position with carbon-13 and then examining the decarbonylated product to locate the isotopically enriched positions by 13c NMR spectroscopy. It is shown that the carbon monoxide initially eliminated is a cobalt carbonyl and the ketonic CO migrates from its apical position onto a cobalt atom. </p> <p> A second project involves the synthesis and characterization of a cobalt cluster derived from the reaction of dicobalt octacarbonyl with the insecticide DDT . This cluster contains the bis(4-chlorophenyl)methylcarbynyl capping group which is so bulky that it has the potential to stop the rotation of the carbynyl ligand and also prevent carbonyl exchange on the metal triangle. The DDT-tricobalt cluster was characterized by X-ray crystallography. The compound crystallizes in the space group P21/n: the monoclinic cell has dimensions a = 13.083 A, b = 14.222 A, c = 14.165 A, B = 95.871 degrees and Z = 4. The molecule adopts almost Cs symmetry except that the phenyl rings are twisted slightly so as to destroy the potential mirror plane. At low temperature, the cobalt carbonyl ligands are non-equivalent on the NMR time-scale and the possible causes for this behaviour are discussed. </p> / Thesis / Master of Science (MSc)

<p>Veno-arterijski gradijent ugljen-dioksida (Pv-aCO2) se smatra pokazateljem adekvatnosti microcirculatornog venskog protoka. U stanjima usporenog protoka dolazi do povećavanja Pv-aCO2 zbog fenomena zadržavanja CO2. Vrednost Pv-aCO2 predložena je kao dodatni cilj rane usmerene terapije kod pacijenata sa septičnim &scaron;okom. Cilj rada bilo je utvrditi postojanje korelacije promene Pv-aCO2 s promenom SOFA (&ldquo;Sequential Organ Failure Assessment&rdquo;) skora (delta SOFA) nakon primene rane ciljane terapije, kao i korelacije vrednosti različitih pokazatelja krvnog protoka unutar prvih 12 sati od početka lečenja pacijenata sa sepsom. Sekundarni cilj bilo je utvrditi postojanje korelacije Pv-aCO2 6 sati nakon početka rane ciljane terapije (T6) s dužinom boravka u intenzivnoj jedinici i ishodom lečenja. Prospektivnim, neintervencijskim ispitivanjem obuhvaćeno je 150 pacijenata sa sepsom ili septičnim &scaron;okom. Merenja serumskog laktata, saturacije kiseonikom me&scaron;ane venske krvi (ScvO2) i Pv-aCO2 vr&scaron;ena su na početku rane ciljane terapije (T0), posle 6 i 12 sati (T6, T12). Pv-aCO2 se računao kao razlika između parcijalnog pritiska ugljen dioksida arterijske i me&scaron;ane venske krvi. Vrednost SOFA skora određivana je u vremenu T0 i nakon 48 časova (T48). Pacijenti su za potrebe analize podeljeni u dve grupe na osnovu promene SOFA skora [(1) pacijenti kod kojih je do&scaron;lo do smanjenja SOFA skora (delta SOFA &lt; 0); (2) pacijenti kod kojih je smanjenje SOFA skora izostalo (delta SOFA &ge; 0)] i na osnovu vrednosti Pv-aCO2 u vremenu T6 [(1) pacijenti sa visokim Pv-aCO2 (&ge; 0.8 kPa); (2) pacijenti sa normalnim Pv-aCO2 (&lt; 0.8 kPa)]. Između dve grupe pacijenata, sa normalnim i visokim Pv-aCO2, statistički značajne razlike uočene su samo u odnosu na najvi&scaron;u vrednost respiratorne komponente SOFA skora (p=0.01). Uočena je statistički značajna korelacija između vrednosti Pv-aCO2 i laktata u vremenu T6 (r=0.2), Pv-aCO2 i ScvO2 u vremenu T0 (r=-0.4) i T12 (r=-0.24) kao i laktata i ScvO2 u vremenu T0 (r=-0.26) i T12 (r=-0.18). Analizom ponavljanih merenja nije utvrđena statistički značajna korelacija između promene vrednosti Pv-aCO2 unutar prvih 6 sati s promenom SOFA skora unutar prvih 48 sati nakon početka rane ciljane terapije (p=0.12). Utvrđeno je da su vrednosti Pv-aCO2 u vremenu T6 bile lo&scaron; prediktor smrtnog ishoda. Nisu utvrđene statistički značajne razlike u dužini boravka u intenzivnoj jedinici i ishodu lečenja u zavisnosti od vrednosti Pv-aCO2.</p> / <p>Central venous-arterial CO2 difference (Pv-aCO2) reflects adequacy of microcirculatory venous flow. Widening of Pv-aCO2 due to CO2-stagnant phenomenon is described in the low flow states. Pv-aCO2 was proposed as an additional resuscitation target for patients with septic shock.The aim of this study was to examine correlation between changes in Pv-aCO2 and SOFA score as well as different blood flow indices (lactate, mixed venous oxygen saturation) 12 hours after onset of resuscitation in patients with sepsis or septic shock. Secondary aim was to evaluate association of delta CO2 6 hours after onset of resuscitation and patient outcomes (length of stay in the ICU, mortality). Prospective observational study included 150 patients with sepsis. Simultaneous measurements of lactate, mixed venous oxygen saturation (ScvO2) and delta PCO2 were performed at onset of resuscitation (T0) and after 6 hours (T6). Delta PCO2 was calculated as a difference between arterial PCO2 and PCO2 from mixed venous blood. Organ dysfunction was evaluated with the Sequential Organ Failure Assessment (SOFA) score at T0 and after 48 hours (T48). Mortality was assessed after 28 days. For data analysis purposes two groups were created based on delta SOFA [(1) patients with SOFA score decrease (delta SOFA &lt;0); (2) patients without SOFA score decrease (delta SOFA &ge; 0)] and based on Pv-aCO2 [(1) patients with high Pv-aCO2 (&ge;0.8 kPa); (2) patients with normal Pv-aCO2 (&lt;0.8 kPa). Patients with high and normal Pv-aCO2 differed only with respect to highest respiratory SOFA score (p=0.01) Change in Pv-aCO2 between T0 and T6 was not in correlation with change in SOFA score between T0 and T48 (p=0.12). Moderate statistically significant correlation was found between Pv-aCO2 and lactate at T6 (r=0.2), and moderate inverse correlation between Pv-aCO2 and ScvO2 at T0 (r=-0.4) and T12 (r=-0.25) and ScvO2 and lactate at T0 (r=-0.27) and T12 (r=-0.18). Pv-aCO2 at T6 was not associated with 28-day mortality and length of stay in the ICU.</p>

<p>UVOD: Maligni tumori reproduktivnih organa nalaze se među vodećim uzrocima obolevanja i umiranja od malignih bolesti žena, kako u svetu, tako i u Srbiji. Jedan od najvažnijih puteva &scaron;irenja ovih bolesti je limfogeni, a konvencionalna radiolo&scaron;ka dijagnostika limfnih čvorova kod ovih pacijentkinja je neprecizna. Funkcionalna radiolo&scaron;ka dijagnostika, uključujući i magnentno rezonantnu sekvencu difuzionog kretanja (DWI) i iz nje izvedenu ADC mapu koja omogućava kvantitativnu analizu difuzionih osobina unutar limfnog čvora, daju obećavajuće rezultate u mogućnosti razlikovanja benignih od maligno izmenjenih limfnih čvorova male karlice i ingvinuma kod pacijentkinja obolelih od malignih tumora ženskih polnih organa. CILJ: Cilj studije je 1. utvrđivanje dijagnostičkih mogućnosti magnetnorezonantne sekvence difuzionog kretanja (DWI) u razlikovanju benignih od maligno izmenjenih limfnih čvorova male karlice i ingvinuma kod pacijentkinja obolelih od malignih tumora ženskih polnih organa, poređenjem preoperativno načinjenog magnetnorezonantnog pregleda i postoperativnog patohistolo&scaron;kog nalaza; 2. analiza povezanosti osobina metastatski izmenjenih limfnih čvorova na sekvenci difuzionog kretanja (DWI) i gradusa primarnog tumora, i 3. utvrđivanje uticaja tehničkih karakteristika sekvenci difuzinonog kretanja (DWI) na magnetnorezonantu procenu metastatske infiltracije karličnih i ingvinalnih limfnih čvorova i postoperativnog patohistolo&scaron;kog nalaza. MATERIJAL I METODE: Istraživanje je sprovedeno u periodu od 2013. do 2016.godine, kao prospektivna klinička studija u Centru za radiologiju, na Operativnom odeljenju Zavoda za ginekologiju, Klinike za ginekologiju i aku&scaron;erstvo i u Zavodu za patologiju Kliničkog Centra Vojvodine u Novom Sadu. Studija je obuhvatila 80 pacijentkinja obolelih od malignih tumora vulve, vagine, grlića materice, tela materice i jajnika. Na osnovu lokalizacije malignog tumora sve ispitanice su razvrstane u 5 grupa: grupa A- 3 žene obolele od carcinoma vulve, grupa B- 1 žena obolela od karcinoma vagine, grupa C-32 pacijentkinje obolele od karcinoma grlića materice, grupa D- 30 pacijentkinja obolelih od malignih tumora tela materice i grupa E- 14 žena obolelih od malignih tumora jajnika. Procena stadijuma bolesti definitivno je izvr&scaron;ena posle operacije na osnovu histopatolo&scaron;kog pregleda kompletnog hirur&scaron;kog materijala uključujući i pregled uklonjenih limfnih čvorova na osnovu aktuelne FIGO klasifikacije stadijuma bolesti zasebno za svaku pojedinačnu lokalizaciju malignog tumora. Svim pacijentkinjama je preoperativno načinjen magnetnorezonantni pregled male karlice na uređaju za magnetnu rezonancu 1.5 T General Electric Signa HDx u Centru za radiologiju, Kliničkog centra Vojvodine. Kod istih pacijentkinja naknadno je sprovedeno standardno hirur&scaron;ko lečenje po protokolu hirur&scaron;kog lečenja za dato maligno ginekolo&scaron;ko oboljenje sa karličnom i/ili ingvinalnom limfadenektomijom. Postoperativno je izvr&scaron;ena patohistolo&scaron;ka analiza hirur&scaron;ki uklonjenog materijala i limfnih čvorova razdvojenih po anatomskim grupama u karlici i ingvinalnoj regiji. REZULTATI: Ukupno 2320 limfnih čvorova je mapirano i patohistolo&scaron;ki pregledano kod 80 pacijenata. Metastaze u limfnim čvorovima patohistolo&scaron;ki su verifikovane kod 28 pacijenata (35%). Kod ovih 28 (35%) pacijentkinja, 152 (27,28%) od ukupno 557 limfnih čvorova bilo je metastatski izmenjeno na patohistolo&scaron;kom pregledu. Metastaze u limfnim čvorovima utvrđene su kod 2 pacijentkinje (7,14%) sa karcinomom vulve, 11 (39,28%) sa karcinomom cerviksa, 9 (32,14%) sa tumorima tela materice, te 6 (21,42%) sa tumorima jajnika. Od 28 pacijentkinja kod kojih su utvrđeni pozitivni limfni čvorovi, 14 pacijentkinja (50%) imalo je dobro diferentovan primarni tumor, 8 (28,57%) srednje diferentovan, dok je 6 (21,42%) imalo lo&scaron;e diferentovan primarni tumor. Od ukupno 152 metastatski izmenjena limfna čvora u na&scaron;oj studiji, 8 limfnih čvorova (5,26%) pripadalo je ingvinalnoj grupi od čega 5 (3,289%) povr&scaron;noj ingvinalnoj, a 3 ( 1,97%) dubokoj ingvinalnoj grupi, 8 (5,26%) parametrijalnoj grupi, 48 (31,58%) opturatornoj grupi, 40 (26,31%) spolja&scaron;njoj ilijačnoj grupi, 36 (23,684%) unutra&scaron;njoj ilijačnoj grupi, dok je 12 (7,89%) pripadalo zajedničkoj ilijačnoj grupi karličnih limfnih čvorova. Kraći prečnik limfnog čvora nije pokazao značajnu razliku između metastatskih ( mean &plusmn; SD, 8,3 &plusmn; 5.4 mm, raspon , 4.5-30 mm ) i limfnih čvorova koji nisu bili metastatski izmenjeni ( 6,3 mm &plusmn; 1,5 , 4,5-9,6 mm ; P= 0,191 ). Izmerena ADC vrednost bila je značajno niža kod metastatski izmenjenih limfnih čvorova (mean &plusmn; SD , ADC: 0,8725 x 10-3 mm2/s &plusmn; 0,0125) nego kod limfnih čvorova koji nisu bili metastatski izmenjeni (mean &plusmn; SD, ADC: 1,116 x 10- 3 mm2/s &plusmn; 0,1848; P=0,001). Prosečne vrednosti ADC kod b =800 s/mm2 i b =1200 s/mm2 nisu se značajno razlikovale između metastaski izmenjenih limfnih čvorova (mean &plusmn; SD, ADC: 0,8575 &plusmn; 0,0125 x 10-3 mm2/s, ADC:0,8859 &plusmn; 0,0125 x 10-3 mm2/s) i limfnih čvorova koji nisu metastatski izmenjeni (mean &plusmn; SD, ADC:1,0345 &plusmn; 0,1222 x 10-3 mm2/s, ADC:1,1125 &plusmn; 1638 x 10-3 mm2/s; P =0,657 i P = 0,877). Ako se koristi vrednost ADC od 0,860 x 10- 3 mm2 / s kao kritična vrednost za razlikovanje metastatskih od limfnih čvorova koji nisu metastatski izmenjeni, senzitivnost DWI MR iznosila je 89%, specifičnost 85% i ukupna tačnost 86%. Pozitivna prediktivna vrednost (PPV) DWI MR u detekciji limfnih metastaza u karličnoj i ingvinalnoj regiji iznosila je 30%. Negativna prediktivna vrednost (NPV) testa iznosila je 99%. Pozitivna prediktivna vrednost (PPV) MR zasnovana na kriterijumu ADC vrednosti značajno je veća u odnosu na sve kriterijuma veličine (P &lt; 0,001). Negativna prediktivna vrednost MR zasnovanoj na kriterijumima veličine limfnog čvora i na ACD vrednosti nisu se međusobno statistički značajno razlikovali (P&lt;0,05). Performanse dijagnostičke metode (MR) bile su značajno bolje za minimalnu ADC vrednost od svih kriterijuma baziranih na veličini limfnih čvorova ( P=0.001 za minimalnu ADC vrednost u odnosu na sve druge kriterijume). MRI na osnovu definisanog modela koji kombinuje kriterijum ADC vrednosti sa kriterijumom veličine ima sledeće dijagnostičke performanse za diferencijaciju malignih od benignih limfnih čvorova: senzitivnost od 95%, specifičnost 92%, sveukupna tačnost od 92,5%, pozitivnu prediktivnu vrednost od 46% i negativnu prediktivnu vrednost od 99.6%. ZAKLJUČAK: Kriterijum veličine limfnog čvora nije dovoljno precizan pokazatelj metastatske invazije limfnih čvorova. Sekvenca difuzionog kretanja (DWI) uvek se mora analizirati zajedno sa ADC mapom i visoko rezolutivnim T1 i T2 otežanim magnetnorezonantnim sekvencama. Studijom je dokazan visok stepen povezanosti između preoperativnog određivanja metastaske infiltracije karličnih i ingvinalnih limfnih čvorova malignih tumora ženskih polnih organa primenom sekvence difuzionog kretanja (DWI) i postoperativnog patohistolo&scaron;kog nalaza. Uz graničnu ADC vrednost od 0,860 x 10-3 mm2/ s, senzitivnost MRI DWI u otkrivanju metastatskih limfnih čvorova iznosi 89%, a specifičnost 85%. Kombinacija ADC vrednosti i morfolo&scaron;kih karakteristika limfnih čvorova konvencionalnim magnentno rezonantnim pregledom je najprecizniji prediktor postojanja metastatske infiltracije karličnih i ingvinalnih limfnih čvorova kod pacijentkinja sa malignim tumorima ženskih polnih organa. Tehničke karakteristike sekvenci difuzionog kretanja (DWI) u smislu razlike u visokim b vrednostima ne utiču na magnentno rezonantnu procenu metastatske infiltracije karličnih i ingvinalnih limfnih čvorova kod pacijentkinja sa malignim tumorima ženskih polnih organa. Studijom nije utvrđena statistički značajna razlika između preoperativno utvrđenih ADC vrednosti metastatski izmenjenih limfnih čvorova i stepena histolo&scaron;ke diferencijacije ovih tumora. Sekvenca difuzionog kretanja (DWI) je brza, jednostavna, neinvazivna metoda koja značajno doprinosi dijagnostičkim mogućnostima magnetne rezonance u razlikovanju benignih od malignih limfnih čvorova male karlice i ingvinuma.</p> / <p>INTRODUCTION: Malignant tumors of reproductive organs are among the leading causes of morbidity and mortality in women, both in Serbia and worldwide. Lymphatic spread is one of the most important pathways of tumor dissemination. However, conventional lymph node imaging in these patients is imprecise. Functional imaging, including diffusion-weighted magnetic resonance imaging (DWI MRI) and derived ADC map which allows quantitative analysis of diffusion parameters within a lymph node, provide promising results in discrimination benign from malignant pelvic and inguinal lymph nodes in patients with gynecological malignancies. AIM: Aim of the study was: 1. To assess diagnostic performances of DWI MRI in differentiation between benign and malignant pelvic and inguinal lymph nodes in patients with gynecological malignancies, by comparison of preoperative magnetic resonance and postoperative histopathological findings. 2. To analyze correlation between DWI characteristics of metastatic lymph nodes and grade of the primary tumor, and 3. To evaluate the influence of technical characteristics of DWI sequences on MR assessment of metastatic pelvic and inguinal lymph node and postoperative histopathological findings. MATERIAL and METHODS: The prospective clinical study was conducted in Center for Radiology, Surgery Department of Clinic for Gynecology and Obstetrics and Pathology Department of Clinical Center of Vojvodina from 2013 to 2016. It comprised 80 patients with malignant tumors of vulva, vagina, uterine cervix and body and ovaries. Based on the localization of the tumor, all patients were divided into 5 groups: group A-3 patients with vulvar cancer, group B- 1 patient with vaginal cancer, group C- 32 patients with cervical cancer, group D- 30 patients with uterine body tumors and group E- 14 patients with malignant ovarian tumors. Staging of the disease was performed after surgery based on histopathological examination of complete surgical specimen, including examination of removed lymph nodes, based on current FIGO classification separately for each primary tumor location. Preoperatively, all patients underwent MRI examination (1.5 T General Electric Signa HDx) at Center for Radiology, Clinical Center of Vojvodina. The same patients underwent standard surgical treatment according to the treatment protocol regarding the tumor type and stage, with complete pelvic and/or inguinal lymphadenectomy. Histopathological examination of surgically removed material and lymph nodes separated in pelvic and inguinal anatomic groups was performed after the surgery. RESULTS: The total of 2320 of lymph nodes were mapped and histopathologically examined in 80 patients included in the study. Metastases in lymph nodes were histopathologically confirmed in 28 patients (35%). In these 28(35%) patients, in 152 (27,28%) out of 557 lymph nodes histopathological examination confirmed metastases. Lymph node metastases were confirmed in 2 patients (7.14%) with vulvar cancer, 11 (39.28%) with cervical cancer, 9 (32.14%) with uterine body tumors and 6 (21.42%)patients with ovarian tumors. In 28 patients with positive lymph nodes, 14 patients (50%) had well differentiated primary tumor, 8 (28.57%) moderately differentiated, while 6 (21.42%) patients had poorly differentiated primary tumor. Out of 152 metastatic lymph nodes in our study, 8 lymph nodes (5.26%) were inguinal ( 5 (3.289%) superficial inguinal and 3 ( 1.97%) deep inguinal group), 8 (5.26%) were parametrial, 48 (31. 58%) obturatory, 40 (26.31%) external iliac, 36 (23.684%) internal iliac, while 12 (7. 89%) belonged to common iliac pelvic lymph nodes group. Shorter lymph node axis did not show significant difference between metastatic ( mean &plusmn; SD, 8.3 &plusmn; 5.4 mm, range , 4.5-30 mm ) and benign lymph nodes ( 6.3 mm &plusmn; 1.5 , 4.5-9.6 mm ; P= 0.191 ). Measured ADC values were significantly lower in metastatic (mean &plusmn; SD , ADC: 0.8725 x 10-3 mm2/s &plusmn; 0.0125) than benign lymph nodes (mean &plusmn; SD, ADC: 1.116 x 10-3 mm2/s &plusmn; 0.1848; P=0.001). Mean ADC values at b =800 s/mm2 and b =1200 s/mm2 did not differ significantly between metastatic (mean &plusmn; SD, ADC: 0.8575 &plusmn; 0.0125 x 10-3 mm2/s, ADC:0.8859 &plusmn; 0,0125 x 10-3 mm2/s) and benign lymph nodes (mean &plusmn; SD, ADC:1.0345 &plusmn; 0.1222 x 10-3 mm2/s, ADC:1.1125 &plusmn; 1638 x 10-3 mm2/s; P =0.657 i P = 0.877). If ADC value of 0.860 x 10- 3 mm2 / s is determined as a cut off value for discrimination of benign and malignant lymph nodes, DWI MRI sensitivity was 89%, specificity 85% and overall accuracy was 86%. Positive predictive value (PPV) of DWI MR in detection of pelvic and inguinal lymph node metastases was 30%. Negative predictive value (NPV) of the test was 99%. MRI PPV based on ADC value criteria was significantly higher compared to all size-based criteria (P &lt; 0,001). MRI NPV based on size based and ADC values criteria did not differ significantly (P&lt;0,05). Performances of diagnostic method (MRI) were significantly better for minimal ADC value compared to all lymph node size-based criteria ( P=0.001 for minimal ADC value compared to all other criteria). Combination of ADC value criteria and size-based criteria yields MRI the following diagnostic performances in discrimination between benign and malignant lymph nodes: sensitivity 95%, specificity 92%, overall accuracy 92.5%, positive predictive value 46% and negative predictive value 99.6%. CONCLUSION: Lymph node size is not sufficiently precise criteria for determination of metastatic lymph node involvement. DWI sequence always needs to be evaluated together with ADC map and high resolution T1W and T2W magnetic resonance sequences. The study shows high correlation between preoperative assessment of pelvic and inguinal lymph node metastases from gynecological malignancies using MRI DWI and postoperative histopathological findings. With a cut off ADC value of 0.860 x 10-3 mm2/ s, sensitivity of MRI DWI in metastatic lymph node detection is 89%, while specificity is 85%. Combination of ADC values and morphological lymph nodes characteristics assessed by conventional MRI is the most precise predictor of metastatic pelvic and inguinal lymph node invasion in patients with gynecological malignancies. Technical characteristics of DWI i.e. different high b-values do not influence MR assessment of metastatic pelvic and inguinal lymph node involvement in patients with gynecological malignancies. The study did not confirm statistically significant difference between preoperatively measured ADC valued of metastatic lymph nodes and histological grade of primary tumors. DWI MRI sequence is fast, simple, noninvasive method which aids significantly to MRI diagnostic performances in discrimination between benign and malignant pelvic and inguinal lymph nodes.</p>