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Purpose: The impact of acute changes in atrial loading conditions and the influence of atrial fibrosis on it’s function is not well understood. We aimed to study the effects of acute reversal of LA volume overload and the relation between atrial fibrosis and echo indices of LA function in patients with mitral regurgitation (MR). Methods: We studied 13 patients in sinus rhythm undergoing cardiac surgery for severe MR. An intraoperative TEE exam including Tissue Doppler Imaging (TDI) was acquired pre- and immediately post-procedurally. LA biopsies were obtained during surgery and stained with Mallory’s trichrome to assess for fibrosis. Results: A nonsignificant reduction in LA volumes occurred after surgery. The LA emptying index (EI) (151.8±93.0 vs. 87.6±34.1%, p=0.02) and LA passive emptying fraction (39.5±14.3 vs 23.2±9.3%, p

Ascending colon cancer as a colocutaneous fistula to the abdominal wall at the site of a previous postoperative scar is extremely rare. A 69 year old male presented with five day history of pain and foul smelling discharge from right subcostal scar from elective cholecystectomy performed 8 years ago. Last three days, he had fever up to 39 degrees C, with mild pain in right upper abdominal quadrant without vomiting, diarrhea, bloody stools or weight loss. Computed tomography, with peroral contrast, revealed extralumination into abdominal wall with several fistulas reaching the skin. Emergency median laparotomy found infiltrating tumor of ascending colon into abdominal wall. A right hemicolectomy and complete thickness abdominal wall excision (7 x 10 cm) was performed. The abdominal wall defect was too extensive for primary closure and two 20 x 20 cm moist gauzes were placed to cover the defect and were fixed with stitches to the skin. On second postoperative day, due to contamination, porcine dermal collagen implant was placed intraperitoneally. Such emergency presentations and therapeutic options are discussed.

After RFA surgery conversion to SR is not synonymous with normal atrial contraction as described by reduced wall motion velocities and low velocity of atrial transport. Our results imply that long term postinterventional SR maintenance improves coordinated atrial activation with enhancement of contraction over time. Fibrosis which is a hallmark of adverse atrial tissue remodeling, proved to be a negative precursor of impaired atrial contractile and reservoir function.

Hodgkinova bolest razlikuje se od svih drugih bolesti na temelju svojeg celularnog sastava:manjine neoplastičkih stanica (RS stanice i njihove varijante u upalnoj pozadini) i većine stanica ove pozadine (limfocita). U ovoj pilot studiji provedena je analiza ekspresije kaspaze 3 metodama imunohistokemije u kohorti od 29 bolesnika liječenih od MH NS1 stadija inicijalnom kemoterapijom i konsolidacijskom radioterapijom regija limfonoda zahvaćenih bolešću, u periodu od 1983-1999. godine u KBC Zagreb. Analizom preživljenja bolesnika ustanovljeno je postojanje tendencije razlika u skupinama bolesnika u kojih su Hodgkinovi limfomi imali različiti ekspresiju ovog izvršnog efektora apoptoze. Navedena pilot studija sugerira potrebu provođenja ovog translokacijskog istraživanja na većoj skupini bolesnika, kako bi se nevedene uočene razlike potvrdile.

Impact of current treatment protocol on survival of high-risk patients with isolated congenital diaphragmatic hernia (CDH) – experience without extracorporeal membrane oxygenation

Outcome of postoperative treatment in newborns with congenital anomalies of digestive system and abdominal wall - 16 years of experience

Diferencijalna dijagnoza novorođenačke dispneje obuhvaća mnoge plućne bolesti, sistemne bolesti, neuromišićne bolesti te prirođene anomalije pluća, dišnih putova, koštanog dijela prsnog koša i dijafragme koje ugrožavaju izmjenu plinova smanjujući respiracijsku površinu.Prikazujemo novorođenče koje je zbog krajnje velike cistične duplikacije ileuma u prvim satima života razvilo dispneju i zatajenje disanja. Značajno smanjenje plućne rastezljivosti u ovom je slučaju bilo posljedica kompresivnog efekta crijevne duplikature na normalan prenatalni plućni razvoj i postnatalnu plućnu ekspanziju. Ovakva klinička slika dosad je isključivo opisivana u slučajevima intratorakalnog prisustva abdominalnih organa. Predlažemo da se i duplikacije crijeva uvrste u stanja koja mogu uzrokovati tešku dispneju i u najranijoj novorođenačkoj dobi.

Lipid peroxidation (LPO) has important role in colon carcinogenesis, while acrolein was found to be associated with transition of benign into malignant colon tumors. Our recent findings also show the increase of acrolein-protein adducts in the non-malignant colon epithelium in the vicinity of colon carcinomas. To see if this process of aldehyde based LPO damage affects also nucleic acids we used recently developed monoclonal antibody (mAb21) against the acrolein-modified DNA, which recognizes mostly acrolein modified 2'-deoxyadenosin (dA). Following tumors were analyzed: 1) tubular adenomas (N=10), 2) villotubular low grade adenomas (N=23), 3) villotubular high grade adenomas (N=18), 4) Duke's A carcinomas (N=19), Duke's B carcinomas (N=10) and Duke's C carcinomas (N=12) as well as 9 samples of normal colon and 33 colon tissue samples around carcinomas. In normal colon epithelium nuclear acrolein-dA positivity could hardly be found at all, while weak cytoplasmic immunopositivity was noticed often. In tumorous epithelium cytoplasmic acrolein-dA immunopositivity increased gradually with grade of dysplasia from benign tubular adenomas to carcinomas. Cytoplasmatic immunopositivity was high in carcinomas irrespective of the tumor grade (Dukes A, B or C). On the contrary, the level of nuclear acrolein-dA was higher in less dysplastic adenomas (tubular adenomas and low-grade villotubular adenomas), than in high-grade villotubular adenomas and colon carcinomas. Consequently, for advanced carcinomas (Dukes B and C) identical raise of both cytoplasmatic and nuclear acrolein-dA adducts was observed. As in case of previously described acrolein-protein aducts, acrolein-dA adducts confirmed the spread of LPO from carcinoma into adjacent non-malignant colon epithelium.

One of prognostic factors known as Nottingham Prognostic Index (NPI), which is combination of known prognostic factors such as tumor size, grade and axillary node status, is recently in usage in some European countries in clinical practice in prediction of breast carcinoma patients' survival. Therefore, the aim of this study was to verify, according to our experience, the prognostic significance of Nottingham Prognostic Index (NPI) in breast carcinoma patients in association with other new prognostic factors. In this study 148 consecutive specimens of breast carcinoma patients were analyzed. The following data for each patient were collected: age, tumor size, histological grade, axillary lymph node status, overall survival, estrogen (ER), progesterone (PR) receptor expression as well as expression of bcl-2, Ki-67, nm23, HER-2/neu, and p53. The Nottingham Prognostic Index (NPI) was calculated from the pathological information and patients were grouped according to the standard NPI index into: good prognostic group (GPG), moderate prognostic group (MPG), and poor prognostic group (PPG). The correlation of prognostic groups according to the NPI with other prognostic and predictive factors such as age, ER, PR, p53, bcl-2, Ki-67, nm23, Ki-67, Cathepsin D and HER-2/neu on overall survival was analyzed. The results of univariate analysis showed statistically significant correlation between patients' age, NPI prognostic groups and stage of disease with patients survival. When other prognostic factors were correlated with NPI prognostic groups there was not additional prognostic discrimination in given prognostic groups. Only marginally statistically significant influence of p53 expression was found on patient survival between MPG and PPG. It seems that other prognostic factors in combination with NPI prognostic groups do not have in our group of patients practical clinical relevance for the management of patients with breast carcinoma.

From 1991-2004, 4452 newborns were admitted in our NICU. Surgica procedures were performed for abdominal wall and alimentary system anomalies in 283 (6, 4%). Duration of their postoperative treatment was 8916 days (mean duration was 31, 5 days, 35 days for survivors, 23 days for deceased). 214 (78%) newborns were healed or recovered and 59 (22%) died. This is the largest group of patients with congenital anomalies of alimentary system and abdominal wall treated in the single hopital in Croatia. These results of short-term survival (to discharge from hospital) are encouraging, and we have followed improvement of survival thought these years. The investigations on prenatal diagnosis of anomalies and the impact of place of birth (level of neonatal care) on final outcomes in these patients are in process.

Aim To assess the frequency and types of histopathological changes in placentas from pregnancies complicated by preeclampsia/eclampsia. Methods Placentas routinely sent for pathological examination (n=1, 689) were studied microscopically and compared to findings of 50 placentas from uncomplicated pregnancies. Results Out of 1, 689 placentas from singleton pregnancies, 279 (16.5%) were from pregnancies complicated by preeclampsia/eclampsia. Seventy five placentas (26.8%)were appropriate for gestational age ; other findings included: infarcts of various stage and volume in 63 cases (22.6%), minimal hypoxic damage in 27 cases (9.7%), accelerated maturation in 42 cases (15.1%), chronic villitis in 18 cases (6.5%), mixed findings in 18 cases (6.5%), intervillous thrombosis in 15 cases (5.4%), subchorial thrombosis in 9 cases (3.2%), immaturity of the villi in 6 cases (2.1%), and findings suggestive of placental insufficiency in 6 cases (2.1%). Normal findings were significantly more frequent in the control group (P

Recent investigations found that acrolein, a lipid peroxidation product, could be rapidly incorporated into proteins, generating a carbonyl derivative as a marker of oxidative stress to proteins. Acrolein, an aldehyde that can be ubiquitously generated in biological systems, is extremely reactive and accumulates in a form covalently bound to proteins in vivo. Due to its biological effects it is considered to be a potent factor of carcinogenesis in particular if based on exogenous or iatrogenic pathology (cigarette smoking, dietary factors, etc.). As it is well known the colon carcinogenesis is influenced strongly by oxidative stress and lipid peroxidation, which was especially well documented for 4-hydroxynonenal, we studied possible differences in distribution of acrolein-protein adducts in human colon tissue and different types of tumors. Monoclonal antibody (acrolein-KLH antibody mAb5F6) was used at 2  g/ml on tissue sections of formalin-fixed paraffin embedded specimens that were deparaffinized, hydrated, and stained using a modified avidin– biotin peroxidase immunohistochemistry. Following tumors were analyzed: 1) tubular adenomas (N=24), 2) vilotubular low grade adenomas (N=24), 3) vilotubular high grade adenomas (N=20), 4) Duke’ s A carcinomas (N=19), Duke’ s B carcinomas (N=11) and Duke’ s C carcinomas (N=15) as well as 13 samples of normal colon tissues samples. The results obtained have shown that normal colon tissue, both epithelium and stroma are occasionally positive for acrolein. However, acrolein positivity was significantly less frequent in tubular and vilotubular low grade adenomas increasing gradually to normal distribution in high grade vilotubular adenomas and Duke’ s A stage carcinomas. Advanced stages of carcinomas (Duke’ s B and C) were again associated with less obvious acrolein presence in the tissues. Interestingly in Duke’ s A carcinomas the incidence of acrolein in malignant cells’ nuclei was more pronounced than in advanced stages of carcinomas (B & C). According to these findings we assume that, similar to 4-hydroxynonenal, acrolein may also play an important role in colon carcinogenesis both in early stage tumor development and its further progression. To understand further role of the aldehydes, both acrolein and 4-hydroxynonenal in colon carcinogenesis additional studies also on their physiological roles in cell growth control are needed.

Naši rezultati podržavaju postojanje premalignih žljezdanih promjena, a koji se mogu potvrditi imunohistološkim promjenama. Pri tom je vrlo bitan nalaz odnosno potvrditi postojanje c-myc protoonkogena u slučaju određivanja ne samo zloćudnih stanica nego i utvrditi displastične promjene endocervikalnih struktura.

Do danas još nije dokazano postojanje prekursora endocervikalnih žljezdanih promjena. Ova studija pokušala je određivanjem statusa ploidnosti, proliferativne aktivnosti i prisutnosti c-myc onkoproteina u morfološkom normalnom kao i u displastičnom i zloćudno promjenjenom tkivu vrata maternice odrediti postojanje zloćudnog potencijala. Analizirano je 49 reprezentativnih histološki uzoraka vrata maternice kojji na istom mjestu imaju normalne endocervikalne žlijezde kao i displastično i maligno promjenjeni endocervikalni epitel. Rezultati ove studije pokazali su da su morfološki normalne endocervikalne stanice diploidne, da imaju normalnu proliferativnu aktivnost i nemaju prisutan c-myc onkoprotein. Statistička analiza hi kvadratom pokazala je značajnu povezanost zloćudno promjenjenih endocervikalnih stanica s aneuploidnošću /p=0.008/ i povišenom proliferativnom aktivnošću /p=0.0042/. Kako je 1/3 displastičnih stanica diploidna i ima povišenu mitotsku aktivnost, vrlo je vjerojatno da imaju zloćudni potencijal u sebi. Statistička analiza hi kvadratom također je pokazala značajnu povezanost displastičnog endocervikalnog epitela s prisutnošću c-myc onkoproteina /p=0.028/. Dobiveni rezultati podupiru postojanje prekursorskih promjena adenokarcinoma vrata maternice, te naglašavaju potencijalnu ulogu imunohistokemijskog određivanja prisutnosti c-myc onkoproteina u određivanju displastičnog promijenjenog endocervikalnog epitela sa zloćudnim potencijalom.

An increased incidence of cervical invasive primary adenocarcinoma has been noted. The malignat potential was determined by assesing the ploidy status, proliferative activity and c-myc expression separately in normal, dysplastic and malignant endocervical cells from 49 patients. Statistics showed a significant association between dysplastic and malignant cells in ploidy status, proliferative activity and c-myc oncogene expression.

Prognostičko značenje TGF beta u fokalnoj segmentalnoj glomerulosklerozi

Although the patients with diploid and lower S-phase have higher survival, statistically significant difference even in regard to histological type of carcinoma have not been found

Pathogenesis of focal segmental glomerulosclerosis(FSGS)is not resolved.It is assumed that TGF-beta might be involved in the formation of extracellular matrix resulting in interstitial fibrosis and glomerular lesions of FSGS.The aim of our study was to analyze TGF-beta expression considering pathohistological findings and clinical course.TGF-beta expression was determined using mouse monoclonal antibodies and estimated semiquantitively in 51 patients with biopsy proven FSGS.The degree of tissue damage was determined morphometrically as degree of glomerular sclerosis and interstitial fibrosis.Significantly positive correlation was found between TGF-beta expression and irreversible histological changes of glomeruli(R=0.414 ; p=0.024).Also the patients with severe degree of interstitial fibrosis showed significantly greater TGF-beta expression than those with mild or moderate fibrotic changes(R=0.531 ; p=0.0061).Greater TGF-beta expression was found in patients with severe proteinuria(>3.5 g/day)which is one of the indicators of unfavorable prognosis(p>0.05). On the basis of our results it could be concluded that TGF-beta is a cytokine that might influence natural course of FSGS.It is speculative whether increased expression of TGF-beta might be of prognostic value in individual cases.The greater expression of TGF-beta was found in the patients with clinical and histological signs of advanced disease.

Does TGF-ß play a role in the pathogenesis of idiopathic focal segmental glomerulosclerosis

Electron microscopy(EM)has quite often an essential role in the diagnosis of certain tumours and some other diseases, for example Langerhans cell histiocytosis.Ultrastructural analysis is especially important in the differential diagnosis of poorly differentiated mesenchymal and occasionally epithelial tumours, when immunohistochemistry is negative or dubious. This study is based on the investigation of over 250 various tumours that have been sent to our laboratory during the period of the last 15 years.All the material was primarily fixed in 10% buffered formaldehyde, postfixed in 1% osmium tetroxyde for 2 hours and then left overnight in 3% uranyl acetate(UA)for better contrast.For rinsing of tissue phosphate buffer with pH 7.3 was used in all cases.Dehydration was performed in series of acetones and then the tissue was embedded in Durcupan.Ultrathis sections were stained with 4% UA and lead citrate, or by hot UA at 90 oC(When we wanted to study microfilaments), and then analyzed and photographed by electron microscope OPTON EM 9A. We wanted to show the cytoplasmic organelles and various components of cytosceleton and extracellular matrix which are specific for certain tumours or represent the ultrastructural signs of tumour differentiation.They include some typical organelles and modifications of tumour cell surface, various types of microfilaments and some characteristic cytoplasmic or extracellular inclusion bodies that were in most cases the crucial finding for the final diagnosis.

TGF-ß is a multifactorial cytokine with an important role in formation of extracellular matrix whose over-expression results in glomerulosclerosis and tubulointerstitial fibrosis accelerating renal disease progression. ACE gene polymorphism can be assumed to affect it since angiotensin II stimulates its expression. The aim of the study was to analyze TGF-ß expression with regard to the rate of histologic changes and ACE gene polymorphism. The TGF-ß expression determined using murine monoclonal antibodies was estimated semiquantatively (no expression-N, weak-W, moderate/strong-M) in 21 patients with FSGS. Histologic changes were classified as mild, moderate and severe. ACE gene polymorphism was determined by PCR method. TGF-ß expression was not found in 4 out of 5 patients with mild lesion, but it was found in 5 out of 9 patients with moderate lesion. M was present in 3 out of 7 patients with severe lesion, and W was present in 4 patients. DD genotype was found in 6 patients, with the following TGF-ß expression:N-1, W-3, M-2, while the distribution in 11 patients with ID genotype was N-1, W-3, and M-4. N-1, W-2 and M-1 were established in 4 patients with II genotype. Increased TGF-ß expression was observed in patients with FSGS and severe histologic changes. ACE gene polymorphism does not show clear correlation with TGF-ß expression, which is possibly a consequence of a low number of patients.

The study analyzed of 113 patients with invasive carcinoma of cervix treated in the period 1980-1995. Only lymph node metastases significantly influenced survival.

Karcinom želuca spada među najčešće maligne bolesti u svijetu i treći je na svjetskoj ljestvici uzroka smrti od malignih oboljenja. Iako se ukupna incidencija karcinoma želuca smanjuje unazad proteklih nekoliko desetljeća, zabrinjava porast incidencije difuznog podtipa kod kojeg unatoč značajnom napretku u dijagnostici i liječenju nažalost nije postignut značajniji pomak u pronalasku učinkovite terapije. Iako je patogeneza adenokarcinoma želuca predmet mnogobrojnih istraživanja, molekularni profil difuznih karcinoma želuca još uvijek predstavlja veliku zagonetku. Cilj disertacije bio je istražiti promjene proteina obitelji Dishevelled, Secreted frizzled-related proteina i čimbenika transkripcije TCF-1, molekularnih komponenti signalnog puta Wnt, u difuznim karcinomima želuca i usporediti rezultate s patološkim i kliničkim parametrima. Učinjenom imunohistokemijskom i stereološkom kvantitativnom analizom na 62 uzorka difuznih karcinoma želuca i 62 kontrolna uzorka zdravog tkiva želuca utvrđena je statistički značajna razlika u izraženosti proteina SFRP1, SFRP3, TCF-1, DVL2 i DVL3. Izraženost SFRP1, SFRP3 u tumorskom tkivu bila je značajno manja odnosu na zdravo tkivo, dok je izraženost DVL2, DVL3 i TCF-1 u tumorskom tkivu bila značajno veća u odnosu na zdravo tkivo. Za niti jedan protein nije utvrđena statistički značajna razlika u izraženosti u odnosu na kliničke i patološke karakteristike pacijenata. Dobiveni rezultati ukazuju na značajnu ulogu komponenti signalnoga put Wnt u razvoju difuznog kracinoma želuca te predstavljaju temelj za daljnja istraživanja., Gastric cancer is one of the most common malignancies in the world and the third leading cause of cancer-associated death worldwide. Although the overall incidence of gastric cancer has declined rapidly over the recent few decades, increase in the incidence of the diffuse subtype is concerning in which, despite significant advances in diagnosis and treatment, no significant progress has unfortunately been made in finding an effective therapy. Although the pathogenesis of gastric adenocarcinoma is the subject of numerous studies, the molecular profile of diffuse gastric cancer is still a big mystery. The aim of this dissertation was to investigate changes in protein expression of Dishevelled family, Secreted frizzled-related protein (SFRP) and transcription factor TCF-1, the molecular components of the Wnt signaling pathway, in diffuse gastric cancers and compare results with pathological and clinical parameters. Immunohistochemical and stereological quantitative analysis of 62 samples of diffuse gastric cancer and 62 control samples of healthy gastric tissue revealed a statistically significant difference in the expression of SFRP1, SFRP3, TCF-1, DVL2 and DVL3 proteins. The expression of SFRP1, SFRP3 in tumor tissue was significantly lower compared to healthy tissue, while the expression of DVL2, DVL3 and TCF-1 was significantly higher in tumor tissue compared to healthy tissue. No statistically significant difference in expression was found for any of the proteins in relation to the clinical and pathological characteristics of the patients. The obtained results indicate a significant role of the Wnt signaling pathway components in the development of diffuse gastric carcinoma and represent the basis for further research.