Ecstasy tablets intoxication with lethal autcome

Background. Ecstasy, 3,4-methylenedioxymethamphetamine (MDMA), is a synthetic compound increasingly popular as a recreational drug. Tablets known as ecstasy contain MDMA, but may also contain caffeine, ephedrine, paramethoxyamphetamine, 3,4-methylenedioxyamphetamine (MDA), amphetamine, methamphetamine, and ketamine. After absorption MDMA is metabolized to MDA, 4-hydroxy-3- metoxymetamphetamine (HMMA) and 4-hydroxy-3- metoxyamphetamine (HMA). After that HMMA and HMA are conjugated and excreted by urine. The aim of this report was to confirm by toxicological post mortem analyses of poisoned person organs that ecstasy had been the cause of his death. Case report. We reported the death of a 17-year-old boy after the ingestion of ecstasy. MDMA and metabolites were determined by multicolumn high performance liquid chromatography with UV spectral detection (HPLC-UV). Toxicological tests showed the presence of MDMA in all samples. When examining post mortem material (the organs), the highest concentrations were measured in the stomach (835,97 μg/g) and kidney (801,14 μg/g). The minimal concentration was in the liver (22,26 μg/g). Conclusion. The obtained results of MDMA and its metabolites concentrations showed abuse of a high dose of ecstasy.

The impact of architectural and urban patterns on the behaviour of an exhibited angular size-illusion

This paper continues a research in which it has been confirmed that the angular size-illusion underpins a contradictory effect related to a seeming size-decrease of focused architectural and urban objects as the observer approaches them. It explores the impact of various architectural and urban patterns on the behavior of an angular size-illusion noticeable during movement. To obtain sustainable conclusions, real locations are selected and simplified. Simplification criteria are defined respecting the preconditions necessary to trigger such an illusion. Also, two groups of parameters are formulated, both as illusion quantifiers and illusion qualifiers (such as descriptors and determinants). By analyzing the illusion quantifier's conduct, the established valorization criteria allowed the methodological investigation of influences of illusion determinants on the descriptor's behavior. The outputs-based conclusions are generalized in a form applicable to contemporary architectural and urban practice, making it possible to estimate and control the behavior of the illusion in reality

Regulacijski mehanizmi ekspresije vaskularnoga endotelnog čimbenika rasta u karcinomu bubrega : doktorska disertacija

Uvod: Angiogeneza, ili stvaranje novih krvnih i limfnih žila, je neophodna za rast i progresiju tumora, a karcinom bubrežnih stanica idealan model za evaluaciju novih strategija antiangiogene terapije zbog njegove bogate vaskularizacije i visoke ekspresije angiogenih čimbenika. Jedan od najvažnijih promotora angiogeneze je vaskularni endotelni čimbenik rasta ( VEGF) i njegove srodne molekule. VEGF je prekomjerno eksprimiran i na razini mRNA i na proteinskom nivou u humanim tumorima, a brojni čimbenici kroz intracelularne signalne puteve mogu regulirati njegovu pojavnost uključujući hipoksiju i regulatorni transkripcijski faktor HIF1 α, citokine , hormone te modulatore protein kinaze C. Mehanizmi VEGF ekspresije uz sudjelovanje tumor supresorskih gena kao što je p53 ili čimbenika rasta kao na primjer epidermalnog čimbenika rasta (EGF) samo su djelomično poznati. Cilj ovog istraživanja je određivanje imunohistokemijskog izražaja VEGF-A i VEGF-C u svijetlostaničnim karcinomima bubrežnih stanica ( SKBS) u usporedbi s okolnim normalnim tkivom bubrega, te utvrđivanje ekspresije regulacijskih čimbenika HIF1 α, receptora za epidermalni čimbenik rasta (EGFR), p53 tumor supresorskog proteina u tumorskom tkivu uz utvrđivanje odnosa ovih proteina sa angiogenim faktorima VEGF-A i C te odnosa VEGF-A sa gustoćom novostvorenih patoloških krvnih žila. Cilj je također utvrditi metodom fluorescentne in situ hibridizacije da li postoji amplifikacija gena za EGFR u SSKBS te napokon usporediti angiogenezu i ove čimbenike regulacije angiogeneze s kliničko-patološkim parametrima kao što su nuklearni gradus, Ki67 indeks proliferacije tumorskih stanica, veličina tumora, patološki stadij i petogodišnje preživljenje. Materijal i postupci: Na standardnim rezovima 93 SKBS određena je gustoća krvnih žila imunohistokemijskom metodom uz korištenje antitijela CD31 za endotel i na istim rezovima uspoređena sa imunohistokemijskim izražajem VEGF-A.. Izražaj proteina VEGF-A, VEGF-C, HIF1 α, EGFR 1, p53, istražen je metodom imunohistokemije na tkivnim mikroarejima (TMA) istih SKBS-a te uspoređen standardnim statističkim metodama međusobno kao i s kliničkopatološkim parametrima. Metodom fluorescentne in situ hibridizacije (FISH) vizualizirana je amplifikacija EGFR gena u 43 odabrana tumora koji su pokazivali različitu ekspresiju ovog receptora na razini proteina u tumorskim stanicama. Rezultati: Gradus tumora i stadij bolesti su kao glavni prognostički faktori pokazali inverznu korelaciju u odnosu na preživljenje. Studija gustoće krvnih žila u usporedbi s ekspresijom VEGF-A na standardnim rezovima pokazala je da su tumori s vrlo visokom ekspresijom VEGF-A (>75%) povezani s manjim brojem krvnih žila (p=0,034). Na TMA je potvrđena promjenjiva ekspresija sva tri analizirana proteina u tumorskim stanicama SSKBS-ova. Angiogeni čimbenici pokazali su međusobnu povezanost (p<0,031), a njihova ekspresija se uočavala kao perimembranozno ili difuzno citoplazmatsko obojenje. Nuklearna ispoljenost HIF1α (n HIF1α) pokazivala je obrnutu povezanost s difuznim citoplazmatskim obojenjem VEGF-A (p=0,002) i VEGF-C (p=0,053), dok je citoplazmatska ekspresija HIF1α ( cHIF1α) pokazivala pozitivnu korelaciju s difuznim obojenjem oba angiogena čimbenika (p<0,001 odnosno p<0,001). U usporedbi s kliničkopatološkim parametrima, prekomjerna ispoljenost citoplazmatskog cHIF1α i difuznog citoplazmatskog VEGF-A bila je udružena s višim nuklearnim gradusom (p=0,006 odnosno p<0,001), većim tumorima (p<0,001 odnosno p<0,001), višim stadijem bolesti (p=0,023, odnosno p=0,0027) te kraćim preživljenjem (p=0,018, odnosno, p=0,024). Nasuprot tome prekomjerna ekspresija nHIF1α kao i perimembranozna ispoljenost VEGF-C su bili povezani s boljim dijagnostičkim parametrima kao što su niži nuklearni gradus (p=0,006, odnosno, p<0,001 ), manji tumori (p=0,057, odnosno, p= 0,007) i dulje preživljenje ( p=0,005, odnosno,p=0,008). Nadalje, ispoljenost nHIF1α je pokazivala pozitivnu korelaciju s indeksom proliferacije (p=0,022). Veća ekspresija tumor supresorskog proteina p53 bila je povezana sa većim tumorima (p=0,007),višim nuklearnim gradusom ( p=0,048) i stadijem bolesti (p=0,036), kao i veći izražaj EGFR koji je kroz histoskor korelirao s višim nuklearnim gradusom ( p=0,0002) s većim tumorima (p=0,018) višim pT(p=0,036) te kraćim preživljenjem (p=0,046) kod tumora koji su pokazivali samo kontinuirano membransko bojenje. p53 je pokazivao pozitivnu povezanost sa postotkom ekspresije VEGF-C ( (p=0,037), a EGFR je bio proporcionalan sa postotkom difuznog izražaja VEGF-A/C te obrnuto proporcionalno povezan sa postotkom perimembranoznog izražaja. FISH metoda je uočila povezanost polizomije 7 i prekomjerne membranske ekspresije EGFR u SSKBS. Zaključak: Rezultati studije na TMA ukazali su na agresivniji subtip SSKBS-a višeg nuklearnog gradusa koji pokazuje prekomjernu ekspresiju VEGF –A i cHIF1α i na razini multrivarijantne analize što se može smatrati neovisnim prognostičkim značenjem sa mogućim kliničkim implikacijama. Značenje nHIF1α ekspresije povezane sa bolje diferenciranim tumorima i višim proliferativnim indeksom trebalo bi bolje istražiti. Nadalje, subcelularna lokalizacija angiogenih proteina kao i njihovog transkripcijskog faktora pokazala se važnom u odnosu na prognozu bolesti. Naš tumorski model nije potvrdio jednostavnu povezanost VEGF-A i angiogeneze kroz gustoću krvnih žila, ali se i na standardnim rezovima pokazalo da njegova prekomjerna ekspresija predstavlja lošiji prognostički parametar. Difuzna subcelularna lokalizacija VEGF-A i VEGF-C povezana s EGFR najvjerojatnije je povezana sa mehanizmima tumorigeneze.AIM: The role of angiogenesis in the pathogenesis of renal cell carcinoma is well recognized, however the influence of tumor cells in this activity is still not well-known. First, the purpose of this investigation was to analyze and correlate the immunohistochemical pattern of vascular endothelial growth factor (VEGF) expression with the average of microvessel density (MVD) and other clinicopathologic parameters in clear cell renal cell carcinoma (CCRCC) in order to determine its prognostic significance. Secondly we wanted to expand our knowledge on expression of VEGF-A and to compare its value with the VEGF-C expression recognized to be involved in lymph vessel neoangioegenis. Furthermore, the aim was to analyze expression of both angiogenic factors in comparison to Hypoxia inducible factor-1α ( HIF-1α), a regulatory factor of angiogenic switch, p53 tumor supresor protein and epidermal growth factor receptor (EGFR) which are involved in tumor pathogenesis, and finally all analyzed parameters were compared with clinicopathological characteristics of CCRCC including the patients’ survival. We also wanted to investigate the role of EGFR gene copy number changes in relation to EGFR overexpression by means of fluorescence in situ hybridization (FISH). MATERIAL AND METHODS: This study includes tumor specimens of CCRCC obtained from patients undergoing nefrectomy at the Department of Urology, Clinical Hospital Center Rijeka from 1989-1994. All cases were reviewed using WHO tumor classification criteria. First part of our investigation was performed on surgical specimens of 93 CCRCC wich were immunohistochemically analyzed on parafine embedded , whole slide, standard sections for VEGF expression, MVD with anti-CD31, and Ki 67 proliferative index. Then, the tissue microarrays (TMA) were built from the same reviewed cohort of 94 archive formalin fixed and paraffin embedded CCRCC. Immunohistochemistry was performed on tissue microarrays for VEGF-A, VEGF-C, HIF- 1α and Ki67,p53 and EGFR expression. The staining was evaluated as a percentage of cytoplasmic, membranous or nuclear positive tumor cells, and as a histoscore (HS). Clinicopathologic data obtained from patient medical records and from files of the Department of Pathology, Rijeka University School of Medicine, Rijeka, Croatia included sex, age, tumor size, TNM stage, histologic subtype and nuclear grade as assessed using Fuhrman nuclear grading system. RESULTS: On the whole tumor slides, VEGF expression was recorded as the percentage of positive tumor cells(≥75% and ≤75%) and as diffuse or perimembranous VEGF expression according to cytoplasmic distribution. Statistical analysis showed that tumors with ≥75% of VEGF expression were characterized by lower MVD value (p = 0.034), higher nuclear grade(p = 0.018), and higher Ki 67 proliferation index (p = 0.023). Moreover, a higher nuclear grade of tumor cells was characterized by diffuse cytoplasmic VEGF distribution (p = 0.005). The TMA analysis showed the variable expression of analyzed protein in tumor cells among different CCRCC. Both angiogenic factors demonstrated perimembranous or diffuse cytoplasmic staining, with diffuse pattern positively associated (p<0.001). Nuclear HIF-1α expression (nHIF-1α) showed inverse correlation with diffuse cytoplasmic VEGF-A (p=0.002) and VEGF-C (p=0.053), while cytoplasmic HIF-1α expression (cHIF-1α) showed positive correlation with diffuse staining of both angiogenic factors (p<0.001; p<0.001, respectively). In comparison to clinicopathological characteristics, a higher nuclear grade (p=0.006; p<0.001, respectively), larger tumor size (p=0.009; p=0.015, respectively), higher stage (p=0.023; p=0.027, respectively) and shorter survival (p=0.018; p=0.024, respectively) were associated with overexpression of diffuse cytoplasmic VEGF-A and cytoplasmic HIF-1α expression. In contrary, overexpression of nHIF-1α was associated with better diagnostic parameters i.e. lower nuclear grade (p=0.006), smaller tumor size (p=0.057), and longer survival (p=0.005). Expression of p53 protein was recorded as percentage of nuclear positivity /500 tumor celss. Overexpression (≥ of median score 40.5%) was connected with biger tumors, higher NG and pT stage (p=0.007, p=0.048, p=0.036 respectively). Intesive membranous EGFR expression in tumors was also related to worse prognostic parameters and lower overal survival (Hscore p=0.046) EGFR showed higher expression in relation to diffuse cytoplasmic distribution of VEGF-A/C but was negatively associated with perimembranous expression of VEGF-A/C. FISH method revealed polisomy 7 associated with protein EGFR overexpression in CCRCC tumor cells. Multivariate analysis underline NG and diffuse cytoplasmic HIF-1α as an independent prognostic factors. CONCLUSION: Study on standard CCRCC tumor slides did not confirm the postulated simple relationship between VEGF overexpression and angiogenesis through high microvessel count. However, the study results indicated that overexpression of VEGF was a worse histologic prognostic parameter in CCRCC. Survey of CCRCC with TMA technique highlights more aggressive subtype of CCRCC with overexpression of VEGF-s and cHIF- 1α, p53 and EGFR in tumors cells that might have some clinical implication. A significance of nHIF-1α expression, associated with better differentiated tumors should be further better understood. FISH analysis showed that EGFR gene dosage can influence on protein ekspresion through polisomy rather than amplification

Uticaj demografskih i socioekonomskih nejednakosti na reproduktivno zdravlje žena

SAŽETAK- Uvod: Zdravstveno stanje žena rezultat je složene interakcije mnogobrojnih faktora. Identifikacija tih faktora, analiza zdravlja žena, rana dijagnoza i pravovremeno, adekvatno, efikasno lečenje i upravljanje kvalitetom zdravlja i kvalitetom života su odlučujići činioci koji utiču na smanjenje nejednakosti u reproduktivnom zdravlju žena. Cilj: Cilj studije je ispitivanje demografskih i socioekonomskih nejednakosti u reproduktivnom zdravlju žena starosti 15 i više godina u Srbiji. Materijal i metod: Za rezultate ove doktorske disertacije korišćen je uzorak od 7864 osoba ženskog pola starosti ≥15 godina iz Nacionalnog istraživanja zdravlja stanovništva Srbije tokom 2013. godine sprovedenog od strane Ministarstva zdravlja i Republičkog instituta za javno zdravlje Srbije, a poštujući metodologiju Evropskog istraživanja zdravlja – drugi talas (EHIS-wave 2). Rezultati: Rezultati istraživanja pokazali su da 62,8% žena u Srbiji ima svog ginekologa. U ukupnom uzorku žena 56,2% njih je bilo seksualno aktivno. Posmatrano prema demografskim i socioekonomskim karakteristikama, žene reproduktivne dobi, iz vangradskih naselja (39,2%), udate (45,0%) i zaposlene (39,1%) značajno češće koriste nesigurne metode kontracepcije. Analiza pokazuje statističku značajnost povezanosti unutar demografskih i socio-ekonomskih karakteristika i poseta ginekologu kao i inicijative za skrining preglede. Viši stepen obrazovanja udatih žena, dobra procena sopstvenog zdravlja, zaposlenost i mesto stanovanja u gradu, pozitivni su aspekti reproduktivnog zdravlja žena naših područja, dok su negativni gojaznost i prisustvo hroničnih bolesti. Zaključak: Utvrđivanje i značaj relevantnih činilaca za reproduktivno zdravlje, definisano u granicama savremenog shvatanja reproduktivnog zdravlja, veoma je bitno sa stanovišta zdravstvene politike koja se vodi u uslovima ograničenih resursa. U našoj zemlji to ima poseban značaj, kako zbog negativnog nataliteta, tako i zbog ograničenih resursa.ABSTRACT- Introduction: Women's health is the result of a complex interaction of many factors. Identification of these factors, analysis of women's health, early diagnosis and timely, adequate, effective treatment and management of health and of quality of life are decisive factors influencing the reduction of inequalities in women's reproductive health. Aim: The aim of the study is to examine demographic and socioeconomic inequalities in the reproductive health of women aged 15 and older in Serbia. Material and method: For the results of this doctoral dissertation, a sample of 7 864 females aged 15 and older from the National Survey of Health of the Population of Serbia from 2013 conducted by the Ministry of Health and the Republic Institute of Public Health of Serbia was used, respecting the methodology of the European Health Survey – second wave (EHIS-wave 2). Results: The results of the research showed that 62.8% of women in Serbia have their own gynecologist. In the total sample of women, 56.2% of them were sexually active. Observed according to demographic and socio-economic characteristics, women of reproductive age from suburban settlements (39.2%), married (45.0%) and employed (39.1%) use insecure methods of contraception significantly more often. The analysis shows that there is a statistically significant correlation between demographic and socio-economic characteristics, and gynecologist visits as well as screening initiatives. Highly educated respondents, employed, of good financial status and from urban areas visited gynecologists more often and most often performed screening examinations on their own initiative, compared to the poorest who were most often tested on the advice of a doctor. Conclusion: Determining the relevant factors and their importance for reproductive health defined within the limits of the modern understanding of reproductive health is very important from the point of view of health policy conducted in conditions of limited resources. In our country, this has a special significance, both due to the negative birth rate and due to limited resources

TETRALOGY OF FALLOT: REPORT OF TWO CASES IN OUTPATIENT PRACTICE

Tetralogy of Fallot or Tetras Fallot is a congenital heart disease with cyanosis, which involves four associated anomalies of the heart. As physicians in primary health care of children, we treat and monitor the growth and development of children at risk with special attention. Among them are also the children with tetralogy of Fallot. The aim of this report was to present and compare postnatal status of two children with tetralogy of Fallot. We presented the girl and a boy, approximately the same age, operated at the same surgical clinic. Both patients were without hereditary load. The girl had a milder clinical course without complications. The boy had associated anomalies, cerebrovascular insult, and a reoperation. After complete surgical correction of congenital heart disease, both children are progressing and developing within the normal range for age. ECG of both children showed the signs of right bundle branch block. Our mission is to continue to closely monitor these children and react in case of complications or worsening of recent findings.Key words: Tetralogy of Fallot, postnatal course, pediatric patient, outpatient car

Use of Marlex mesh with methylmethacrylate to repair large full-thickness defects after subtotal sternectomy caused by chondroma

Background. Sternal benign neoplasms are extremely rare. Chondroma is a benign tumor of cartilage and can be single or multiple. Case report. We presented a case of 28-year-old woman with chondroma of the sternum treated by "en bloc" resection of the tumor (subtotal sternectomy). The chest wall defect was repaired by the placement of Marlex mesh and metylmethacrylate ("sandwich method") for stabilization of the thoracic wall. This place was covered with pectoralis major muscle and skin. The postoperative course was uneventful and the wounds healed by primary intention. Conclusion. The functional and cosmetic results in the usage of Marlex mesh with metylmethacrylate to repair a large full-thickness defect after subtotal sternectomy caused by chondroma were good and the patient was able to resume her preoperative level of activity

New WHO histological classification of renal epithelial tumors

Napredak u dijagnostici proveden na temelju morfologije, imunohistokemije i molekularnih metoda doveo je do identifikacije novih entiteta u patologiji bubrežnih tumora. Iz tih je razloga Međunarodno društvo za urološku patologiju (ISUP) preporučilo izmjene klasifikacije tumora bubrega SZO-a 2004. pod nazivom ISUP Vancouver Modifikacija SZO histološke klasifikacije bubrega tumora koja je i službeno, s manjim izmjenama ove, 2016. godine, predstavljena u 4. izdanju SZO-ove klasifikacije tumora mokraćnog sustava i muških spolnih organa. Cilj je ovoga članka kroz pregled literature ukratko predstaviti novu podjelu karcinoma bubrežnih stanica i nove entitete prepoznate po histološkim i genetskim karakteristikama te usmjeriti pažnju na važnost onih osobina tumora koje određuju stupanj i stadij bolesti, a imaju velik prognostički značaj. Nova će klasifikacija omogućiti patolozima da usuglase svoje izvještaje, a ostalim strukama dati uvid u promjene u nalazima patologa.Progress in the diagnostics based on morphology and immunohistochemistry, genetic and molecular methods has led to the identification of new entities in renal tumor pathology. Therefore the International Society of Urological Pathology (ISUP) recommended modifications of the WHO 2004 renal tumor classification and called it ISUP Vancouver Modification of WHO (2004) Histologic Classification of Kidney Tumors which is officially published in new“ blue book“, The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs. The aim of this article was to briefly introduce a new classification of renal cell carcinoma and new tumor entities identified by their histological and genetic characteristics. We also wanted to focus attention on the importance of those characteristics that determine the tumor grade and the stage of the disease, which have prognostic significance. The new classification will allow pathologists to harmonize their reports, and other disciplines to understand the changes in the findings of the pathologist

Chemical Analysis of Mortars of Archeological Samples form Mediana

The aim of this study was mineralogical and chemical analysis of mortar from the floor, ceiling and wall of Stibadium B, from the archaeological site of Mediana. ICP-OES and FTIR-spectroscopy were used to determine chemical composition and some major mineralogical species. The obtained results show that lime mortar is probably used. Large contribution of silicon- and aluminum-oxides, indicate the presence of quartz and clay minerals derived from the aggregate, river sand and crushed bricks. The obtained results also show large amount of iron, manganese and copper. The determinated metals in samples from floor and wall of Stibadium B, are mostly present in oxide fraction, while in sample from ceiling, they are mostly found in silicate fraction

Breast Infiltrating Ductal Carcinoma: Analysis of Hormone, HER-2 Receptors and Ki-67 Proliferation Marker

The aim of this study was to analyse breast carcinomas with discordant receptor status, probably hormonal dependent (estrogen receptor (ER) positive, progesterone receptor (PR) negative or ER-PR+ subgroup profile) infiltrating ductal breast carcinomas not otherwise specified (IDC NOS). Specimens from 90 IDC NOS were grouped into three categories according to hormonal status: dependent (D) (ER+PR+), probably dependent (PD) (ER+PR- or ER-PR+) and non-dependent (ND) (ER-PR-); they were evaluated considering some established prognostic parameters in breast carcinomas. Statistically significant difference was found between tumor receptor status distribution and menopausal status (p= 0.0235), age of the patients (p=0.000467), histological grade (p=0.000003), vascular invasion (p=0.006), HER-2 status (p=0.0039) and Ki-67 proliferation rate (p=0.000311). D tumors were found exclusively in post-menopausal patients (average age 68.9 years), most of which had intermediate (II) grade, without vascular invasion, with HER-2 status score predominantly 0 or 1+ and lower Ki-67 proliferation rate. PD tumors were found predominantly in younger post-menopausal patients (average age 57.5 years), with vascular invasion found in 23% of the cases. ND tumors mostly had higher histological grade, showed the highest percentage of the Ki-67 positive tumor cells and vascular invasion in 30% of the cases. We conclude that the patients with PD breast carcinomas were younger post-menopausal women with the tumors moderately differentiated, HER-2 score 0 or 1+ and with lower Ki-67 proliferation rate