Electrochemical Reduction of Intermediates in the Vitamin B6 Production. II. Reduction of 2-Methoxymethyl-3-nitro-4-methyl- 5-cyano-6-chloropyridine

2-Methoxymethyl-3-nitro-4-methyl-5-cyano-6-chloropyridine (I) was reduced on a mercury-pool in an electrolytic cell with a diaphragm. A mixture of acetic and hydrochloric acid was used as catholyte and diluted hydrochloric acid as anolyte. Compound I was reduced at - 0.5 V to 2-methoxymethyl-3-amino-4-methyl- 5-cyano-6-chloropyridine (II) (yield 67-820/o). Compound II was reduced at - 0.9 V to 2-methoxymethyl-3-amino-4-methyl-5- cyanopyridine (Ill) (yield 54-83-0/o). Compound III was reduced at -1.1 V to 2,4-dimethyl-3-amino-5-cyanopyridine (IV) (yield 48-660/o Compound IV was reduced at constant current density to 2,4-dimethyl-3-amino-5-aminomethylpyridine (V) (yield 82,40/o). Polarographic waves of I, II, and III are defined and character of limiting currents was determined according to the usual criteria

Electrochemical Reduction of Intermediates in the Vitamin B6 Production. II. Reduction of 2-Methoxymethyl-3-nitro-4-methyl- 5-cyano-6-chloropyridine

2-Methoxymethyl-3-nitro-4-methyl-5-cyano-6-chloropyridine (I) was reduced on a mercury-pool in an electrolytic cell with a diaphragm. A mixture of acetic and hydrochloric acid was used as catholyte and diluted hydrochloric acid as anolyte. Compound I was reduced at - 0.5 V to 2-methoxymethyl-3-amino-4-methyl- 5-cyano-6-chloropyridine (II) (yield 67-820/o). Compound II was reduced at - 0.9 V to 2-methoxymethyl-3-amino-4-methyl-5- cyanopyridine (Ill) (yield 54-83-0/o). Compound III was reduced at -1.1 V to 2,4-dimethyl-3-amino-5-cyanopyridine (IV) (yield 48-660/o Compound IV was reduced at constant current density to 2,4-dimethyl-3-amino-5-aminomethylpyridine (V) (yield 82,40/o). Polarographic waves of I, II, and III are defined and character of limiting currents was determined according to the usual criteria

Potential Years of Life Lost Due to Premature Mortality from Cancer in Karlovac County (Croatia), 2006–2010

The aim of this paper was to estimate cancer burden in the Karlovac County using potential years of life lost due to cancer and contribute to setting priorities in cancer control at the local level. Potential years of life lost (PYLL) is an important public health mortality indicator that goes into the category of social indicators and has a great role in the process of health care planning in defi ning priorities for the prevention of premature death. In this paper PYLL is defi ned as the number of years of life lost by persons who died in the age of 1–75. In the period 2006–2010 there were 4118 death in Karlovac County in the 1–75 age group which makes 48204 potential years of life lost, where 33856.5 (70.24%) PYLL referred to men, and 14347.5 (29.76%) PYLL to women. Cancer was responsible for the largest proportion of premature death (33.17%), in which 62.90% of premature death referred to men and 37.10% to women. Lung cancer was the leading cause of premature death due to cancer for men (31.04% of PYLL due to cancer) and the breast cancer for women (17.95% PYLL due to cancer). In the observed period cancer caused the shortening of the average life span of 11.9 years, out of which the biggest loss was caused by melanoma (18.7 years). Population health measures based on PYLL are useful for measuring and monitoring the impact of local efforts to reduce premature mortality

Dipyridamole stress echo – the next step in evolution of stress imaging in the Echocardiography Laboratory at the Čakovec County Hospital

Introduction: Stress echocardiography is the combination of 2D echocardiography with physical, pharmacological or electrical stress. The diagnostic endpoint of the detection of myocardial ischemia is the induction of a transient change in regional function during stress.1 Myocardial ischemia results in a typical “cascade” of events in which the various markers are hierarchically ranked in a well-defined time sequence. Flow heterogeneity between subendocardial and subepicardial perfusion is the forerunner of ischemia, followed by metabolic changes, alteration in regional mechanical function, and only at a later stage by electrocardiographic (ECG) changes, global left ventricular dysfunction (LV) and pain.2 Wall motion and perfusion or coronary flow reserve (CFR) changes are highly accurate, and more accurate than ECG changes for detection and location of underlying coronary artery disease. However, wall motion is more specific and requires ischemia; perfusion changes are more sensitive and may occur in the absence of true ischemia (microvascular disease, or LV hypertrophy).1 The three most common ischemic stressor are exercise, dobutamine, and vasodilators (dipyridamole, adenosine). They are equally potent for inducing wall abnormalities in the presence of a critical epicardial coronary artery stenosis. Dobutamine and exercise manly act through increased myocardial oxygen demand. Vasodilators act by stimulating A2 adenosinergic receptors present on the endothelial and smooth muscle cells of coronary arterioles and induce ischemia due to reduced subendocardial flow supply subsequent to inappropriate arteriolar vasodilatation and steal phenomena.1 Dipyridamole was the first pharmacological stress agent used for the diagnosis of coronary artery disease, with a pioneering indication proposed in Europe for the identification of ischemia during 12-lead ECG3, and later in the USA by Lance Gould as hyperemic stress perfusion imaging.4 Dipyridamole stress echocardiography pioneered in the year of 1985 (Picano et al). The safety record of high dose dipyridamole is well established on the basis of large scale multicentric studies with data from thousands of patients. The incidence of major complications, i.e. myocardial infarction, atrioventricular block, cardiac asystole, sustained ventricular tachycardia, is about 1/1500 cases. The mortality rate is about 1/10000 cases, similar to that of the exercise stress test. Dipyridamole has a better safety profile than when stress testing with dobutamine, where the incidence of major adverse reactions is about 1/300 studies.5 Many centers from 1988 until today, have used high doses administered in a short time (syringe-based infusion of 0.84 mg/kg). Later, some studies were reproduced with these doses, and today, most centers worldwide use high dose delivered in 4-6 min.6 Center experience: In 2017 we started to perform stress echocardiography in Čakovec County Hospital. The first method was exercise echocardiography using treadmill protocol, with imperative do accomplish postexercise imaging as soon as possible (<1 min from the cessation of exercise) where patient moved immediately from treadmill to imaging bed. With this method we have information from exercise stress testing combined with echocardiographic wall motions analysis to make final interpretation. The second method and most used until recently in our echo lab is standard dobutamine stress protocol, starting with 5 ug/kg/min and increasing 10, 20, 30 and 40 ug/kg/min. If no endpoint is reached, atropine, usually in dose 0.25 mg, is added to maximal dobutamine dose infusion. We are using this method for coronary disease detection, but also low dose protocol, to asses myocardial viability, valvular pathology (low-flow aortic stenosis) and other indications. Recently we started vasodilator stress echocardiography using dipyridamole, and until today, we performed a test on 15 patients. Protocol diagram is showed in Figure 1. The dipyridamole dose employed for stress testing was 0.84 mg/kg administered in short time (syringe-based infusion at a rate of 0.21 mg/kg/min during 4 minutes). A fast protocol is embraced because is known that high dose protocols in short time causes a three- to fourfold increase in coronary blood flow in normals and give best sensitivity and specificity for coronary pathology detection7. Peak vasodilatation occurs 1 to 2 minutes after the end of infusion and the dipyridamole elimination half-time is 40 minutes which enables us enough time for imaging in the period of maximum stress. After image completion we give the antidote aminophylline (blocks adenosine receptors) even in negative cases. The antidote can also be used for emergent reversal of adverse dipyridamole-related events which we have not encountered in this limited series of tests. If technically feasible due to image quality, we perform measurement of coronary flow reserve in mid to distal left anterior descending artery (LAD) using pulse doppler (Figure 2 and Figure 3) before and after vasodilatation. CFR in many cases adds additional diagnostic value when combined with conventional wall motion analysis. Another tool to increase diagnostic accuracy, especially when image quality is impaired, are contrast agents (i.e. Optison) which help to delineate endocardial borders. All caffeine-containing foods (coffee, tea, chocolate, bananas, cola drinks) should be avoided for 12 hours before test and all theophylline- containing drugs (aminophylline) should be discontinued for at least 24 hours before test. Very low dose protocols can be used (0.28 ug/kg) to identify myocardial viability and have high specificity (higher than dobutamine) but lower sensitivity8. Absolute contraindications for dipyridamole stress test are active bronchospasm, 2nd or 3rd degree AV block and systolic blood pressure <90 mmHg. Relative contraindications are methylxanthine use and remote history of restrictive airway disease. Conclusion: Dipyridamole stress echocardiography can be used as a preferred stress test for the detection of coronary artery disease in patients unable to exercise and with contraindications to dobutamine (tachyarrhythmias, uncontrolled blood pressure). It is technically easier than exercise or dobutamine stress tests since image quality is less degraded by tachycardia, hyperventilation and hypercontractility. The test is equally accurate in comparison with dobutamine, but technically easier and safer9. In the future, dipyridamole test is planned to be the default method for pharmacological stress in our laboratory supported with contrast agents when necessary. Contrast perfusion stress echocardiography is the next planned step in years to come

Tumori i pseudotumori orbite

Twenty-four orbital tumors and 4 pseudotumors diagnosed in biopsy material among 596 ophthalmic tumors examined during the 1998-2003 period are presented according to patient age and sex, tumor histology and immunohistochemistry. The most common orbital tumors were lipomas, meningiomas and lymphomas, with a peak incidence in the seventh decade of life. Most orbital tumors of childhood are distinguished from those occurring in adults. Most pediatric orbital tumors are benign (developmental cysts, capillary hemangioma, hamartoma), with a peak incidence in the first decade of life. Orbital tumors show a bimodal age distribution. Benign orbital tumors are more common than the malignant ones. Rhabdomyosarcoma (embryonal type) is the most common orbital malignancy in childhood, and lymphoma in adults. Orbital pseudotumors are a term that has been widely accepted to describe inflammatory lesions of the orbital tissue with a mixed inflammatory infiltrate with a varying grade of fibrosis. Histologic classification of orbital pseudotumors is presented. Orbital pseudotumors occur predominantly in older individuals and are infrequent in children and young individuals. These imply a nonspecific inflammatory process of unknown etiology, and have been included as part of the differential diagnosis of orbital tumors.Opisuju se 24 tumora i 4 pseudotumora orbite prema njihovim histološkim i imunohistokemijskim obilježjima, dobi i spolu, dijagnosticirani u biopsijskom materijalu među 624 oftalmičnih tumora u razdoblju od 1998. do 2003. godine. Najčešći orbitalni tumori bili su lipomi, meningeomi i limfomi s vršnom učestalošću u sedmom desetljeću života. Većina orbitalnih tumora dječje dobi razlikuje se od tumora koji se javljaju u odraslih. Tumori dječje dobi većinom su benigni (ciste, kapilarni hemangiomi i hamartomi) s vršnom učestalošću u prvom desetljeću života. Orbitalni tumori imaju bimodalni oblik rasporeda učestalosti. Najčešći zloćudni tumor dječje dobi je rabdomiosarkom (embrionalni tip), a u odraslih limfom. Orbitalni pseudotumori su prihvaćen izraz koji opisuje lezije orbitalnog tkiva s miješanim upalnim infiltratom s različitim stupnjem fibroze. Prikazana je histološka klasifikacija orbitalnih pseudotumora. Orbitalni pseudotumori javljaju se pretežito u starijih osoba, a rijetko u djece i mladih. To su nespecifične upale nepoznatog uzroka koje su uključene kao dio diferencijalne dijagnoze orbitalnih tumora

Neuroblastoma in children

Neuroblastom je najčešći ekstrakranijalni solidni tumor dječje dobi i četvrti po redu od svih pedijatrijskih tumora. Potječe od neuroblasta, pluripotentnih stanica simpatičkog živčanog sustava. Najčešće se primarni tumor nađe u abdomenu, zatim u prsnom košu, a vrat i zdjelica su rjeđe lokalizacije. Bolest se u većine djece prezentira s palpabilnom abdominalnom masom kao prvim znakom bolesti. Ostali znakovi i simptomi bolesti su: kašalj, dispneja, Hornerov sindrom, disfunkcija mokraćnog mjehura i crijeva, neurološki ispadi, bolovi u kostima, orbitalne ekhimoze, povremene temperature, anemija, generalizirana bol itd. Nažalost se, otprilike 70-80% pacijenata starijih od 18 mjeseci prezentira s metastatskom bolešću u limfnim čvorovima, jetri, koži, kostima i koštanoj srži. U dijagnostici neuroblastoma koriste se laboratorijski testovi i slikovne metode za evaluaciju primarne bolesti i njene diseminacije. Dob, stadij i biološke karakteristike tumora su važni prognostički čimbenici koji se koriste u stratifikaciji rizika i u odabiru odgovarajućeg liječenja. Razlike u ishodu bolesti među pacijentima s neuroblastomom su upečatljive. Pacijenti s niskim i intermedijarnim rizikom bolesti imaju odličnu prognozu i ishod. Međutim, oni s visokim rizikom bolesti i dalje imaju vrlo lošu prognozu usprkos intenzivnoj terapiji. Čak i s primjenom visokih doza kemoterapije i autolognom transplantacijom matičnih stanica, manje od polovice pacijenata se izliječi.Neuroblastoma is the most common extracranial solid tumor in children and fourth of all pediatric cancers. It originates from neuroblasts, pluripotent cells of the sympathetic nervous system. The majority of primary tumors occur in the abdomen, then in thorax, seldom in neck and pelvis. Neuroblastoma usually presents with palpable abdominal mass as the first sign of the disease. Other signs and symptoms include: cough, dyspnea, Horner's syndrome, bladder and bowel dysfunction, neurologic disorders, bone pain, orbital ecchymosis, occasional temperature, anemia, generalized pain, etc. Unfortunately, approximately 70-80% of patients older than 18 months present with metastatic disease, usually in the lymph nodes, liver, bone, and bone marrow. The diagnosis of neuroblastoma consists of lab tests and imaging techniques for the evaluation of the primary tumor and its extension. Age, stage and biological features encountered in tumor are important prognostic factors and are used for risk stratification and treatment assignment. The differences in outcome for patients with neuroblastoma are striking. Patients with low- and intermediate-risk neuroblastoma have excellent prognosis and outcome. However, those with high-risk disease continue to have very poor outcomes despite intensive therapy. Less than half of these patients are cured, even with the use of high-dose therapy followed by autologous bone marrow and stem cell rescue

Report on the compliance of concrete with structural design requirements

Donošenjem novog Tehničkog propisa za betonske konstrukcije mijenjaju se postupak i podaci za donošenje završne ocjene kvalitete betona ugrađenog u betonsku konstrukciju. Uspoređeni su postupci prema starom i novom propisu. Vidi se da se postupak po starom propisu bazira više na rezultatima ispitivanja na mjestu ugradnje, a po novom propisu na procedurama i dokumentiranom upravljanju procesima. Donošenje je završne ocjena kvalitete ugrađenog betona po novom propisu zahtjevnije.The approval of the new Technical Regulations for concrete structures has brought some changes in the procedure and the data for the final quality assessment of concrete placed in concrete structures. Procedures based on the new and old regulations are compared. It can be seen that the procedure based on the old regulations is more reliant on in-situ test results, while new regulations rely more on the procedures and on the documented management of procedures. The final assessment of concrete quality after placing is more demanding when based on the new regulations

Development of a capillary electrophoretic method for simultaneous determination of gemcitabine and its impurity

Gemcitabin, 2',2'-difluoro-2'-deoksicitidin, antimetabolit pirimidina, je antineoplastični lijek koji se koristi u liječenju brojnih uznapredovalih ili metastatskih karcinoma kao monoterapija ili u kombinaciji s drugim citostaticima, ovisno o indikaciji. Cilj je ovog istraživanja bio razviti novu, brzu, jednostavnu i ekološki prihvatljivu kapilarnoelektroforetsku metodu za istovremenu analizu gemcitabina i njegovog onečišćenja cizotina. Kao prikladna tehnika odabrana je kapilarna elektroforeza kao "zelena" alternativa već razvijenoj HPLC metodi za određivanje sadržaja gemcitabina i određivanje onečišćenja uvrštenoj u 8. izdanje Europske farmakopeje. Analiza je vršena u kapilari duljine 35 cm (27 cm) pri temperaturi od 25 °C, na valnoj duljini detekcije od 275 i 237 nm. Tijekom razvoja nove metode ispitane su različite vrste radnih pufera: boratni (pH 9,3), fosfatni (pH 7,0) i acetatni (pH 3,0). Na temelju rezultata eksperimenata najbolji puferom pokazao se fosfatni pufer (pH 7,0), dok je bolje razdvajanje i oblik pikova postignut dodatkom veće koncentracije SDS-a. Optimalnim se pokazala 50 mM koncentracija SDS-a. Ispitan je i utjecaj napona na vrijeme analize te razlučivanje između analita. Kod napona od 10 kV postignuto je bolje razdvajanje gemcitabina i citozina. Međutim, primjenom nižeg napona produljuje se vrijeme putovanja analita kroz kapilaru pa je potrebno voditi računa o tome da je razlučivanje između analita što bolje, no istovremeno uz što kraće vrijeme analize. Predlaže se daljnja optimizacija metode kako bi se postiglo prikladno razlučivanje pikova te njihov odgovarajući oblik i simetrija uz što kraće vrijeme analize.Gemcitabine, 2', 2'-difluoro-2'-deoxycytidine, pyrimidine antimetabolite, is an antineoplastic drug used to treat many advanced or metastatic cancers as monotherapy or in combination with other cytostatics, depending on the indication. The aim of this study was to develop a new, fast, simple and environmentally friendly capillary electrophoretic method for simultaneous identification and determination of gemcitabine and its impurity cytosine. Capillary electrophoresis was chosen as a suitable "green" alternative to an already developed HPLC method for the determination of gemcitabine and its impurities included in the 8th edition of European Pharmacopoeia. The analysis was carried out in 35 cm (27 cm) capillary at a temperature of 25 ° C and detection was at 275 i 237 nm. Three different buffers were studied while developing the method: borate (pH 9.3), phosphate (pH 7.0) and acetate (pH 3.0). Based on the experimental results, best buffer was shown to be the phosphate buffer (pH 7.0), while a better separation and peak shape were achieved by adding a higher concentration of SDS. 50 mM SDS was chosen as the optimal concentration. The effect of voltage on the analysis time and resolution between the analytes was investigated. It has been shown that a better separation of gemcitabine and cytosine was achieved at 10 kV. However, applying a lower voltage is prolonging the migration time of the analytes through the capillary. Therefore, it is necessary to take into account that a good resolution is achieved but that the analysis time is not too long. Further method optimization is required to achieve the appropriate peak separation, shape and symmetry with as short analysis time as possible

The Basic Traits and an Analysis of Some Structural Changes among Croats from Žumberak in Cleveland

Prvi hrvatski doseljenici u Cleveland, Ohio, kao dio hrvatskog migracijskog vala u SAD krajem prošlog stoljeća, bili su porijeklom iz gorovitog predjela zapadne Hrvatske zvanog Žumberak. Žumberčani su u svijet odlazili iz specifičnih lokalnih razloga u području porijekla. Kao subetnička skupina Hrvata s vrlo razvijenom nacionalnom sviješću, čvrsto povezani mitom ili realnošću o uskočkom porijeklu i pripadnošću grkokatoličkoj vjeri, u novoj su domovini stvorili svoju naseobinu koja je imala identična obilježja žumberačke zajednice u starom kraju. (Podaci o nupcijalitetu i natalitetu iznijeti u ovom radu vrlo su indikativni u tom smislu.) Na osnovi izvornih podataka iz crkvenih knjiga hrvatske grkokatoličke župe Sv. Nikola u Clevelandu autorica u ovom radu analizira neke promjene u društvenoj strukturi te homogenizirane i zatvorene žumberačke naseobine u vremenu od prvih doseljavanja pa do tridesetih godina ovoga stoljeća. Podaci i izračunate stope nupcijaliteta, nataliteta i mortaliteta tog prvog i dijela drugog naraštaja žumberačkih doseljenika u Cleveland daju relativno točnu sliku o bitnim obilježjima i nekim strukturalnim promjenama njihove naseobine. U radu autorica govori još o tipu žumberačkih migracija u Cleveland, o njihovu prostornom rasporedu u tom gradu, o društvenom okupljanju te o ulozi hrvatske grkokatoličke župe Sv. Nikola u životu clevelandskih Žumberčana.The first Croatian immigrants in Cleveland (Ohio), coming as part of the migration wave to the USA at the end of the 19th century, originated from the mountainous region of western Croatia called Žumberak. The people of Žumberak emigrated due to specific local reasons at home. As a subethnic Croatian group with a highly developed national consciousness, closely bound together by the myth (or reality) of their origin as Uskoks fleeing from the Ottoman advance, as by their Eastern-Rite Catholic religion, in their new homeland they created settlements with identical features as in the land from which they originated. Data on marriages and natality are very indicative in this sense. On the basis of original records from the parish books of the Eastern-Rite Catholic parish of Saint Nicholas in Cleveland, the author analyses some changes in the social structure of this homogeneous and closed settlement of people from Žumberak in the period from the time of the first immigration till the 1930s. The data and calculated rates of marriages, natality and mortality of the first and a part of the second generation of migrants from Žumberak in Cleveland provide a relatively exact picture of the essential traits and some structural changes among them. In the paper, the author also notes the types of migration from Žumberak to Cleveland, the spatial distribution of the immigrants in this city, their social organisation and the role of the parish of Saint Nicholas in their lives

Cerebelarni meduloblastom u muškarca starije životne dobi: neočekivan nalaz

Medulloblastoma is one of the most common primary tumors of the central nervous system in children and quite uncommon in adult age. Clinically, medulloblastomas may be difficult to recognize in the elderly because of their rarity and histologic similarity to common metastatic tumors. Medulloblastomas arising earlier in life occur close to the midline, whereas those arising later in life are located more laterally within a cerebellar hemisphere. This case report presents an unusual appearance of medulloblastoma in an elderly man.Meduloblastom je jedan od najčešćih primarnih tumora središnjeg živčanog sustava u dječjoj dobi, a rijedak u odraslih osoba. Meduloblastome koji se pojavljuju u odrasloj dobi teško je klinički prepoznati zbog njihove rijetke pojavnosti i histološke sličnosti s metastatskim tumorima. Meduloblastomi koji se pojavljuju u dječjoj dobi smješteni su bliže medijalnoj liniji, dok se oni koji se pojave u starijoj životnoj dobi nalaze lateralno unutar hemisfera maloga mozga. Prikazani slučaj predstavlja iznimno rijetku pojavu meduloblastoma u muškarca starije životne dobi, koji je zahvatio gornju površinu maloga mozga i pinealno područje. Većina istraživanja ukazuje na to da radikalan kirurški zahvat i poslijeoperacijsko zračenje imaju najbolji učinak na preživljenje