Nova generacija cepiv HEPAGERIX B® injekcije cepivo proti hepatitisu 8, izdelano z genetskim inženiringom • metoda genetskega inženiringa .izkljucuje prisotnost cloveške krvi • popolnoma varno in široko preizkušeno cepivo • visoko ucinkovito cepivo, ki varuje pred vsemi znanimi podvrstami hepatitisa B in pred hepatitisom D • dosega skoraj' 100 % serokonverzijo_ • lahkp ga dajemo v vseh starostnih obdobjih • vsi ga dobro prenašajo Bazicno cepljenje opravimo s 3 intramuskularnimi dozami po eni izmed shem (O, 1, 6) ali (O, 1, 2): a) osebe, ki so izpostavljene manjšemu ali zmernemu tveganju infekcije: prva doza: dan po izbiri (O) druga doza: mesec dni po prvi dozi (1) , tretja doza: 6 mesecev po prvi dozi (6) b) osebe, ki potrebujejo hitro zašcito ali so pogosteje izpostavljene infekciji: prva doza: dan po izbiri (O) druga doza: mesec dni po prvi dozi (1) tretja doza: 2 meseca po prvi dozi (2) Odrasli in otroci starejši od 1 O let: 20 /-l9 proteina površinskega antigena v 1 ml suspenzije. Novorojencki in otroci do 1 O let: .10 /-lg proteina površinskega antigena v 0,5 ml suspenzije. Podrobnejše informacije in literaturo dobite pri proizvajalcu. .(. KRK. tovarna zdravil, p. o., Novo mesto RADIOLOGY AND ONCOLOGY Established in 1964 as Radiologia Iugoslavica in Ljubljana, Slovenia. Radiology and Oncology is a journal devoted to publication of original contributions in diagnostic and interventional radiology, computerized tomography, ultrasound, magnetic resonance, nuclear medicine, radiotherapy, clinical and experimental oncology, radiophysics and radiation protection. Editor in chief Tomaž Benulic Ljubljana, Slovenia Associate editors Gregor Serša Ljubljana, Slovenia Viljem Kovac Ljubljana, Slovenia Editorial board Marija Auersperg Andrija Hebrang Branko Palcic Ljubljana, Slovenia Zagreb, Croatia Vancouver, Canada Sonja Bebar Ljubljana, Slovenia Duriltt Horvat Zagreb, Croatia ]urica Papa Zagreb, Croatia Matija Bistrovic Zagreb, Croatia Berta Jereb Ljubljana, Slovenia Dušan Pavcnik Ljubljana, Slovenia Haris Boko Zagreb, Croatia Vladimir Jevtic Stojan Plesnicar Malte Clausen Ljubljana, Slovenia Ljubljana, Slovenia Kiel, German y H. Dieter Kogelnik Ervin B. Podgoršak Christoph Clemm Salzburg, Austria Montreal, Canada Miinchen, Germany Ivan Lovasic Miran Porenta Christian Dittrich Rijeka, Croatia Ljubljana, Slovenia Vienna, Austria Marijan Lovrencic Jan C. Roos Ivan Drinkovic Zagreb, Croatia Amsterdan, The Nederlands Zagreb, Croatia Bela Fornet Luka Mi/as Slavko Šimunic Budapest, Hungary Houston, USA Zagreb, Croatia Tullio Giraldi Maja Osmak Andrea Veronesi Udine, ltaly Zagreb, Croatia Gorizia, Jtaly Publishers Slovenian Medica[ Society ­Section of Radiology, Croatian Medica[ Association ­Croatian Society of Radiology Correspondence address Radiology and Oncology Institute of Oncology Vrazov trg 4 61000 Ljubljana Slovenia Phone: + 38 61 314 970 Fax: + 38 61 329 177 Reader f or English language Olga Shrestha Design Monika Fink-Serša Key words und UDC Eva Klemencic Secretaries Milica Harisch Betka Savski Printed by Tiskarna Tone Tomšic, Ljubljana, Slovenia Published quarterly Bank account number 50101 678 48454 Foreign currency account number 50101 620 010 27621 5130/6 LB -Gospodarska banka -Ljubljana Subscription fee for institutions 100 USD, individuals 50 USD. Single issue for institutions 30 USD, individuals 20 USD. 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Indexed and abstracted by: BIOMEDICINA SLOVENICA CHEMICAL ABSTRACTS EXCERPTA MEDICAIELECTRONIC PUBLISHING DIVISION TABLE OF CONTENTS DIAGNOSTIC RADIOLOGY AND ULTRASOUND Radiological aspects of hypertrophic pyloric stenosis Frkovic M, Mandic A 113 Ultrasound guided percutaneous pancreatography (UPP) lvaniš N, Fuckar Ž, Depo/o A, Peric R, Rubinic M, Banic D,Prica M 120 COMPUTERIZED TOMOGRAPHY AND MAGNETIC RESONANCE Possibilities and limitations of computed tomography in diagnosis of thoracic organs Bešlic Š, Dalagija F, Lovrincevic A, lbralic M, Merhemic Z 125 Clinical advances of contrast-enhanced MR imaging Kristl V 130 EXPERIMENTAL ONCOLOGY The response of two vincristine resistant chemotherapeutic drugs Osmak M, Eljuga D human Iarynx carcinoma cell clones to 140 Stability of complex compounds distinguished by different levels in tumorous identical healthy tissues Huljev D, Džajo M, Košutic K, Rajkovic-Huljev Z vs. 145 RADIATION PROTECTION Personnel exposure to radiation at biliary interventional radiological procedures with an overhead tube K6nya A, Vigvdry Z HISTORY OF NUCLEAR MEDICINE AND RADIOLOGY Nuclear medicine in Macedonia -A continous adaptation to the challenge of medical practice Tadžer I The beginnings of radiology in Rijeka Lovasic I 165 REPORTS The 6th postgraduate course on thoracic radiology Debevec M Libri Oncologici -Croation Journal of Oncology Kolaric K 167 169 NOTICES 170 Radio! Onco/ 1992; 26: 113-9. Radiological aspects of hypertrophic pyloric stenosis Marija Frkovic and A. Mandic Clinical Hospital Center Rebro, Department of Radiology, Zagreb, Croatia The authors analyze radiologic methods and diagnostic parameters with special regard to their possibilities and diagnostic characteristics by analyzing hypertrophic pyloric stenosis (HPS) and its differentation from simi/ar pathologic conditions of the aboral part of the stomach in newborns. Key words: pyloric stenosis-radiography Introduction Hypertrophic pyloric stenosis is an acquired obstructive anomaly of the aboral part of the stomach. It is not yet known whether the etio­logic factors already exist during intrauterine development. It is rarely present in the first week of life, more frequently it occurs in the 3 period from 2nd to 8th week after birth. 1­ A congenital anomaly of structure or inade­quate number of ganglionic cells of myenteric plexus of antropyloric part of the stomach4-6 or the enlargement of parietal celi mass of the stomach with hypersecretion1 • 7 are considered to be the etiologic cause of HPS. 8 The stress reactor theory based on the hereditary disposi­tion to react excessively on gastrin1 shows that the etiologic cause of HPS is hypersecretion of gastric acid. Correspondence to: Marija Frkovic, M. D., Clinical Hospital Center Rebro, Department of Radiology, Kišpaticeva 12, 41000 Zagreb, Croatia. UDC: 616.334-007 .271-073.75 The clinical symptoms of hypertrophic pyloric stenosis are non-bile-stained vomiting, regurgi­tation, difficulties with feeding, failure 1o thrive or weight loss. More rare finding is an olive-like palpable "tumor" mass in the epigastric region, and sometimes peristaltic waves on the abdomi­nal wall are seen. Since these clinical signs are not constant nor strictly specific to differentiate hypertrophic ste­nosis from other pathologic conditions of this part of the stomach and to confirm the diagno­sis, radiologic examination is necessary. Radiologic methods and diagnostic parameters The diagnosis of HPS with more or Iess persi­stent clinical symptoms can be made on the basis of the following radiological examinations: ultrasound, plain x-ray roentgenograms of the abdomen and contrast study of the upper ga­ strointestinal tract. Ultrasound shows extended, liquid-content­filled stomach. If the diameter of the pyloric muscle on transversal sections is greater than 11 mm, and is more than 2.5 mm thick ("target Frkovic M and Mandic A 1a 1b tening of the entire pyloric canal, with contrast medium accumulating at one side of the flatte­ rlY:J 1g­ n!:J J Figure l. Radiological diagnostical signs of HPS (16). la -"string sign" and aditional "beak sign" and "tit sign" ( .). lb -"double track sign". "spicula sign" and variations: le -"spicula sign" or "pyloric niche", ld -"diamond sign", le -"spiculated antrum sign". 1f -"lasser curve identation". lg -"funnel-shaped antrum" or "burned-out sign". ( d-duodenum, g-ga­ster). sign") and if on longitudinal sections the canal length is greater than 16 mm, pyloric stenosis is present. 9-11 On plain roentgenogram, a distended sto­mach with unproportionally small amount of gas in the small bowel is often present.12 At barium examination of the upper gastroin­testinal tract in about 70 % of patients, gastroin­testinal reflux is found. 13 A great amount of residual content is present in the stomach and emptying of the stomach is delayed. Typical features of HPS include a narrow, band like, upward directed contrast track in the pyloric lumen ("string sign"), with a peak at the base of the pyloric canal ("beak sign") with peristal­tic tension of the antral wall at the edge of hypertrophied pyloric muscle ("tit sign"). Fur­ther progression results in contraction and fiat-ned lumen, which gives the picture of "double track sign". If muscle hypertrophy is atypical or partial, less characteristic pyloric deforma­tions are found: pyloric ulcus like deformations and their variations ("pyloric niche" or "spicula sign", "diamond sign", "spiculated antrum"), "lesser curve indentation" and "funnel-shaped antrum" or "burned-out pyloric stenosis", 2• 14• 15 schematically presented in Figure l. Diagnostic difficulties can occur due to the fact tha:t in a shorter period one form can change into another, progressive or regressive. In cases of atypical or incomplete hypertrophy it is important to prove that during the passage of peristaltic wave a specific deformity of antro­pyloric area is constant from one roentgeno­gram to the other, and from one examination to the other. Atypical forms regularly develop into complete forms of hypertrophied pylorus. In radiological finding it is important to dif­ferentiate HPS from pylorospasm, partial antral web, ulcer niche and pyloric duplication. Pylorospasm is the narrowing and the defor­mation of pyloric canal, it is not fixed, and it changes during the passage of peristaltic wave. Glucagon test will eliminate possible diagnostic difficulties. Glucagon given i. v. or i. m. during examination of the upper gastrointestinal tract leads to relaxation of pyloric muscle and con­ 17 firms the diagnosis of pylorospasm. 15­ Partial antral web is a duplication of mucosa with smaller or larger orifice which narows the antral part of the stomach so that the part of antrum aborally from the web to pylorus can be deformed similarly as in atypical form of hypertrophied pylorus type "burned out pyloric stenosis" or "funnel-shaped antrum". 17-23 So­metimes it is difficult to differentiate these cases even with directoscopic examinations.23 Pyloric or prepyloric ulcer accompanied by regurgitation, gastroesophageal reflux and pe­riulcer edema, can be endoscopically confir­med. In clinical picture in a newborn this pat­hologic status presents with vomiting or hema­ Radiological aspects of hypertrophic pyloric stenosis 27 temesis or periodical bleeding per rectum.25­More constant findings at barium examination of the upper gastrointestinal tract are marked deformity, fixed spasm and edema, while ulcer crater itself sometimes may be visualized and sometimes not. Chronic fibrotic changes in new­borns are not seen. The described changes in radiologic picture can be very similar to pyloric stenosis of short segment marked as "lesser curve indentation". 26 Bleeding ulcer can be confirmed endoscopically and angiographically, and possible perforation will be seen as extralu­mination of contrast medium.27• 28 Duplication of the pylorus is a very rare congenital anomaly.29 In radiological picture it can be similar to atypical presentation of HPS which gives picture of "double track sign" .14 Table l. Demonstration of patients with HPS Patients and methods Due to the pathology of gastrointestinal tract, 141 infants were hospitalized and surgically treated in the Department of Pediatrics in the period from 1987 to 1991. Sixteen of them (11.4 % ) in the age range of 12 days to 8 months underwent surgery due to HPS (Table 1). In ali patients the radiologic diagnosis of HPS was made on the basis of barium examina­tion of gastrointestinal tract. Under TV control we followed perorally given barium to the distal part of the stomach and spot roentgenograms of pyloric region were done. Specific radiologi­cal signs of this pathology were then analyzed and divided into 5 groups: Num-Name Sex Age / Clinical Gastroesopha-RTG signs Radiological ber days diagnosis geal reflux ofHSP diagnosis 1 BM M 31 HPS + string sign HPS 2 CH M HPS + string sign HPS 3 RM M HPS string sign HPS FM M HPS string sign HPS 5 PL M 21 HPS + spicula sign HPS Ulcus 6 PM M 41 HPS string sign HPS 7 JA M 39 HPS + double Pylorospasm track sign" HPS 8 PA M 32 HPS + string sign HPS 9 RJ F 26 HPS + string sign HPS 10 TN M 28 HPS + lesser curve HPS indentation 11 DM F 31 High ileus + lesser curve HPS indentation 12 HD M 24 HPS + string sign HPS 13 KA M 28 HPS + funnel shaped Antral web antrum HPS 14 ZJ M 236 High ileus + spicula sign HPS 15 KM M 31 HPS funnel shaped HPS antrum 16 SD M 12 High ileus + string sign HPS male: female = 1: 2 p = 2/16 = 0.125 q = 14/16 x 0.875 ll6 Frkovic M and Mandic A Figure 2. Specific radiological signs of HPS: "string sign" (.A..A..A.), "tit sign" (.A..A.) and "beak sign" (.A.). l. "string sign" and accompanied "tit" and "beak" signs, Figure 2. 2. "double track sign", Figure 3. 3. "spicula sign" -"pyloric niche", Figure 4, and etiologically identical variations of this sign "diamond sign", "spiculated antrum", Figure 5. 4. "lesser curve indentation" 5. "funnel shaped antrum" or "burned-out sign", Figure 6. The appearance of these signs and their varia­tions are presented in Figure 1, 16 whereas the analysis of their incidence in radiological fin­dings is given in Table 2. The incidence of gastroesophageal reflux as a less specific, but often present symptom was also analyzed, as well as the relation between clinical diagnosis, results obtained from radiolo­gical examinations and operative diagnosis. Radiological aspects of hypertrophic pyloric stenosis Figure 5. "Spiculated antrum" -atypical form of HPS. Results and discussion HPS is one of the most common diseases in 31 infants which requires surgical treatment.Therefore, our 16 (11.4 % ) patients are repre­sentative sample in a group of children operated on due to gastrointestinal tract pathology. The disease more often appears in male in­fants. The proportion of female diseased infants (p) is 0.125 in the total number of infants with HPS, and the proportion of male infants (q) in the total number of these patients is 0.875. This ratio of 14: 2 according to the relative number of coordination shows that in the total number of 70 boys with HPS there were only 10 girls with the same pathology. Our results correlate 16 with the results presented in literature.3· The symptoms of HPS most frequently occur from 2nd to 8th week of life.3• 16 The average age of our patients was 44 days or 6 weeks respec­tively. Figure 6. "Funnel shaped antrum" (.a. .a.) -it is necessary to differentiate it from partial antral web. Very rarely this condition can present as early as the first week of life of a neonate. In such cases it is more difficult to make correct diagnosis. Such condition is characterized by less specific picture of pyloric stenosis of short segment with mi nima] muscle hypertrophy, Table 2. The incidence of radiological signs of HPS RTG finding Number % gastroesophageal reflux 12 75 string sign and additional signs (tit and beak signs) 9 56.25 double track sign 1 6.25 spicula sign and variations 2 12.5 lesser curve indentation 2 12.5 funnel shaped antrum 2 12.5 Frkovic M and Mandic A which later on develops into a typical pyloric stenosis.17 Etiologically, these forms of HPS are connected with persistent pylorospasm which is a result of neonatal hyperacidity or it is consi­dered to be a secondary manifestation of gastric ulcer which causes antral deformity and which is difficult to differentiate from the real pyloric stenosis.26 Our youngest patient underwent sur­gery at the age of 12 days. Opposite to these newborns are infants which in the neonatal period presented as healthy and 25 HPS developed later.15··28 The finding in these cases is very similar to other typical cases. Also in these infants HPS can be a secondary conse­quence of ulcer disease. The coincidence of the appearance of these 2 conditions together sug­gests that they have etiologically the same cau­se. 26-28 In our opinion it explains HPS findings in our patient Z. J. (No 14, Table 1). It also explains clinically and radiologically evident re­lapse of the disease in patient B. M. (No 1, Table 1) who underwent surgery at the age of 1 month and who was reoperated on when he was 10.5 months old. The relapse of HPS has not been published in literature yet, and it is difficult to explain its etiology under assumption that surgical treatment was correct. However, the recurrence of clinical and radiological fin­ding of "double track sign" which did not respond to drug therapy indicate that if partial pyloromyotomy was done and if the circumstan­ces which caused the first appearance of the disease persist, the recurrence of "phenotype" occurs. The clinical picture is very specific, it deve­lops gradually, and at the tirne of hospitalization it is fully developed. This is confirmed by almost exact clinical diagnosis with which the patient is referred to radiologic examination. Namely, the diagnosis of "high ileus" also inclu­des HPS. Gastroesophageal reflux, often present in pa­tients with HPS, was found in 75 % of our patients, which corresponds to the data known from literature.22 However, we are not inclined to attribute significance to this symptom, be­cause in our opinion it will also occur in iden­tical percentage in all other cases of obstruction at the gastroduodenal level. Analyzing radiological signs of HPS found at barium examination of gastroduodenum, our conclusion is that the finding of the "string sign" (trias of symptoms: "string", "tit" and "beak sign") is absolutely reliable in making the diagnosis of HPS. This sign was found in 56.25 % of our cases. lts finding gives the correct radiological diagnosis. Analagous to the "string sign", very relable and more exact is the parameter of the length of the pyloric canal measured by ultrasonography.9 A deformation which we have marked as "spine sign" results in the cases of partial muscle hypertrophy. For more or less progressive, etiologically identical variations, the variations of these signs ("dia­mond sign", "spiculated antrum ") are being used. These and other radiological signs fre­quently found on examinations of our patients, are not pathognomonic and require certain dif­ferential diagnostic freedom, or additional diag­nostic examinations -glucagon test in the cases suspective of pylorospasm, endoscopic exami­nation in the cases suspective of antral diap­ 16 23 hragm, ulcus and double pylorus.14, , Ali of our patients underwent pyloromyoto­my31 and operative diagnosis of HPS confirmed the clinical and radiological diagnosis. Other pathologic conditions which presented additio­nal cause of high ileus were also treated surgi­cally, but they are not the subject of discussion in this report. Clinically clear cases with specific symptoma­tology can be simply diagnosed at ultrasound.9­ 11 It is not necessary to submit such patients to barium examination of gastroduodenum. How­ever, ultrasound can not sol ve less specific cases of HPS, which at barium examination present with rare signs of HPS. In all unclear cases barium examination of gastroduodenum is necessary because for such rare signs of HPS there are no specific US signs. The possibility of association of another anomalies,32 Figure 4, and preoperative differentiation of HPS from 24 other similar conditions19 -· 29 justify the use of barium examination in newborns in spite of irradiation risk. Radiological aspects of hypertrophic pyloric stenosis References l. Rogers IM, Macgillion F, Drainer IK. Congenital hypertrophic pyloric stenosis: a gastrin hypothesis pursued. 1 Pediatr Surg 1976; 11: 173-6. 2. Schuman FI, Darling DB, Fisher JH. Radiogra­phic diagnosis of congenital hypertrophic pyloric stenosis. 1 Pediatr 1967; 71: 70-4. 3. Mardešic D, Kacic M. Prehrana i bolesti probav­nih organa u pedijatriji. JUMENA Zagreb 1979; 193-200. 4. Day LR. Medica! management of pyloric stenosis. JAMA 1969; 207: 948-50. 5. Friesen SR, Pearse AGE. Pathogenesis of conge­nital pyloric stenosis; histochemical analyses of pyloric ganglion cells. Surgery 1963; 53: 604-8. 6. Rintoul JR, Kirkman NF. The myenteric plexus in infantile hypertrophic pyloric stenosis. Arch Dis Child 1961; 36: 474-80. 7. Spitz L, Zail SS. Serum gastrin levels in congenital hypertrophic pyloric stenosis. 1 Pediatr Surg 1976; 11: 33-5. 8. Karim AA, Morrison JE, Parks TG. The role of pentagastrin in production of canine hypertrophic pyloric stenosis and pyloroduodenal ulceration. Br 1 Surg 1974; 61: 327-32. 9. Stunden RJ, Le Quesne GW, Little KET. The improved ultrasound diagnosis of hypertrophic pyloric stenosis. Pediatr Radio/ 1986; 16: 200-5. 10. Strauss S, Itzchak Y, Manor A, Heyman Z, Graif M. Sonography of hypertrophic pyloric stenosis. AJR 1981; 136: 1057-61. 11. Wilson DA, Vanhoutte JJ. The reliable sonogra­phic diagnosis of hypertrophic pyloric stenosis. 1 Ciin U/trasound 1984; 12: 201-7. 12. Riggs WJr, Long L. The value of the olain film roentgenogram in pyloric stenosis. AJR 1971; 112: 77-82. 13. Shopfner CE, Kalmon EHJr, Coin CG. The diag­nosis of hypertrophic pyloric stenosis. AJR 1964; 91: 796-800. 14. Haran PJJr, Darling DB, Sciammas F. The value of the double track sign as a differentiating factor between pylorospasm and hypertrophic pyloric stenosis in infants. Radiology 1966; 86: 723-5. 15. Swischunk LE, Hayden CKJr, Tyson KR. Atypi­cal muscle hypertrophy in pyloric stenosis. AJ R 1980; 134: 481-4. 16. Swischuk LL. Radiology of the Newborn and Young lnfant. Ilnd Ed. Williams and Wilkins, Baltimore/London 1984; 364-81. 17. Swischuk LE, Hayden CKJr, Tyson KR. Short segment pyloric narrowing. Pylorospasm or pyloric stenosis? Pediatr Radio/ 1981; 10: 201-5. 18. Swischuk LE, Tyson KR. "Burned-out" pyloric stenosis: an elusive gastric outlet obstruction. Ra­diology 1975; 117: 373-79. 19. Campbell DP, Vanhoutte 11, Smith EJ. Partially obstructing antral web -a distinct clinical entity. 1 Pediatr Surg 1973; 8: 723-8. 20. Robinson K. Pyloric stenosis due to a mucosal diaphragm. Br 1 Surg 1967; 54: 397-9. 21. Keramidas DC. Congenital incomplete prepyloric diaphragm in infants and children. Surgery 1974; 75: 690-4. 22. Jinkins JR, Bali TI, Clements JL Jr, Elmer RA, Weens HS: Antral mucosal diaphragms in infants and children. Pedici/ Radio/ 1980; 9: 69-72. 23. Fujioka M, Fisher S, Young LW. Pseudoweb of the gastric antrum in infants. Pediatr Radiol 1980; 9: 73-5. 24. Bell MJ, Ternberg JL, Keating JP, Moedjona S, McAlister W, Shackeford GD. Prepyloric gastric antral web: A puzzling epidemic. 1 Pediatr Surg 1978; 13: 307-10. 25. Bremner CG. The lesser curve pyloric niche. Br 1 Radio/ 1968; 41: 291-5. 26. Mendl K, Jenkins RT, Penlington ER. Gastric ulcer in the newborn and its association with antral spasm resulting in hypertrophic pyloric ste­nosis. Br 1 Radio/ 1962; 35: 831-5. 27. Si tka U, Kosti er J. Akutes Pneumoperitoneum in der Neugeborenenperiode. Z Kinderchir 1974; 14: 382-90. 28. Kelsey D, Stayman JWJr, McLaughlin ED, Me­bane W. Massive bleeding in a newborn infant from a gastric ulcer associated with hypertrophic pyloric stenosis. Surgery 1968; 64: 979-82. 29. Grosfeld J, Boles EJr, Reiner C. Duplication of pylorus in the newborn, a rare cause of gastric outlet obstruction. 1 Pediatr Surg 1970; 5: 365-9. 30. Gysler R, Kundert JG. Pyloric stenosis in an eightmonth-old child. Z Kinderchir 1973; 13: 263-7. 31. Rickham PP. Congenital hypertrophic pyloric ste­nosis. In: Rickham PP and Johnston JH eds. Neonatal Surgery. London: Butterworths, 1970; 271-85. 32. Koch A, Rehbein F. Hypertrophische Pylorusste­nose und bedeutende Fehlbildungen des Magen­Darm-Traktes. Z Kinderchir 1974; 15: 163-8. Radio/ Oncol 1992; 26: 120-4. Ultrasound guided percutaneous pancreatography (UPP) Nikola lvaniš, Željko Fuckar, Arsen Depolo, Relja Peric, Milivoj Rubinic, Duško Banic, Milan Prica Clinical Medica! Center Rijeka, Department of Gastroenterology, Croatia The ultrasound pereutane panereatography (UPP) is a eombination of the ultrasound and radiologieal methods. The use of UPP is indieated in the patients suffering from panereatie deseases sueh as segmentary or eompletely dilated panereatie duet, previously diagnosed by the eonventional ultra sound examination. The method is also indieated in the eases where it is not possible to diagnose the pancreatie duet by endoscopic retrograde panereatography (ERP). This method is extremely important when dealing with deseased panereas, espeeially in planning the surgieal drainage treatment. In the last ten months our hospital has suceessfully dealt with ten guided UPP proeedures without any post-treatment eomplieations or mortality. Key words: panereatie diseases-radiography; ultrasonography Introduction Visualization of the panereatie duet is made posible by means of endoscopie retrograde pan­ereatography (ERP), in eombination with en­doscopic radiologieal methods, first reported by Rabinov in 1965. 1 During the past 25 years, ERP has been introdueed into clinical praetice as a routine diagnostic procedure. Indications for ERP are suspected chronie panereatitis, pancreatic carci­noma and haemorrhagie neerotie panereatitis.2 For ali modem diagnostie proeedures it is often difficult to differentiate ehronic panerea­titis frorn panereatic careinoma. Diagnostie methods in use for this purpose are: conventional ultrasound guided biopsy, Correspondence to: Dr. Nikola lvaniš, Vladivoja Milivoja Lenca 48, 51000 Rijeka, Croatia. UDC: 616.37-073.75:534-8 eomputerized tomography, endoseopie retro­grade panereatography (ERP), cytologieal exa­mination of panereatie juiee, funetional tests, biochemieal examination of blood, determining the concentration of tumour antigens in the blood and ultrasound guided pereutaneous pan­ereatography (UPP). In 1977, Copeberg reported on ultrasono­graphieally guided pereutaneous panereatogra­phy, presenting seans of pancreatic ducts of two cases obtained by this methods. 3 Methods and patients Methods Ultrasound guided percutaneous pantography (UPP) is a eombined ultrasonographic and ra­diologieal method. UPP is praetieable with pa­tients with affeeted pancreas. The entire pan­creas is imaged by eonventional ultrasound exa­mination and the panereatie duet dilated in its U/1rasound guided percu1aneous pancrealography (UPP) entirety or only partly. This is done in patients in whom adequate ERP representation is not possible.4-7 Normal diameter of the pancreatic duet is 3.5 mm in its head and up to 2.5 mm in 9 the body and tail of the pancreas.8• At the Gastroenterology Department of the Interna! Medicine Clinical Hospital in Rijeka UPP is indicated in patients whose pancreatic duet has a diameter of 3 mm or more and in whom ERP has failed. First the patient has to be subjected to complete Iaboratory tests and there must be no counterindication for punctu­re. When the epigastric skin gas been sterilized the pancreas and dilated pancreatic duet are exposed, the puncture point fixed on the skin, anaesthesia administered to the future puncture canal (5 ccm of lidocaine), and then a skin incision of 5 mm is made. The needle is introduced transepigastrically under the guidance of ultrasound. While puncturing, the point of the needle is monitored on the screen of the ultrasound apparatus. When the needle has pierced the pancreatic tissue it is introduced into the pancreatic duet with a short thrust, 2 ccm of pancreatic juice are aspirated, and then 5 ccm of iodic contrast medium instilled (Omnipaq 240). The mandren is reinserted into the needle to prevent regurgitation of the contrast medium and the image of the pancreatic duet is radiolo­gically verified. If necessary, another 2 to 4 ccm of contrast medium are instilled, with repeated radiological scanning of the ductus pancreati­cus, screening the passage of the contrast me­dium through the duodenum. Then the needle is deftly extracted and subsequent radiological seans of the pancreatic duet made in a number of modes. Patients In the period from December 1989 to Septem­ber 1990 11 UPP-s had been carried out. First the patients had to undergo complete clinical examinations and Iaboratory tests, with no diag­noses made. A satisfactory ERP scan of ductus pancreaticus could not be obtained in these patients. By means of conventional sonography of the pancreas a scan of the duet dilatation was obtained. Out of the 11 patients subjected to UPP, there were 8 men and 3 women. Their average age was 44. Results The results obtained by UPP are shown in Table l. Out of the 11 UPP-s, 10 were success­ful, whereas in one patient percutaneous puncturing of the pancreatic duet had not suc­ceeded and the duet could not be scanned. Of the successful UPP-s, in 7 patients the scan shows the pancreatic duet and in other 3 pa­tients the scan shows a small pancreatic pseudo­cyst not communicating with the pancreatic duet. In a previousely taken conventional ultra­sound scan the latter had been interpreted as a dilated part of the pancreatic duet. Of the 7 patients whose pancreatic duet seans are shown, in 5 cases the obtained scan was typical of chronic steno-dilating pancreatitis, and in two cases a scan characteristic of pan­creatic head carcinoma was obtained. Including the 3 patients with seans of minor inflammatory pancreatic pseudocysts, 8 patients in the group suffered from chronic pancreatitis and 2 of them had carcinoma of the pancreatic head. With the UPP-s performed up to now no complications have been observed. After being subjected to UPP-s, for the first 24 hours the patients had been protected by 3 x 750 mg i. m. of Cefuroxim. Table l. Rcsults of 11 UPP UPP (total) II Successfully 10 Unsuccessfully 1 Pancrcatic duet 7 Small pscudocyst 3 Chronic pancrcatitis 8 Pancrcatic carcinoma 2 lvaniš N et a/. Discussion A detailed scan of the entire pancreatic duet is the basic requirment of modem diagnostic pro­cedure for patients with pancreatic complaints. The patients are subjected to the usual proce­dure, including the possibility of ERP use. With some patients, however, there are con­traindications for this kind of endoscopy, the impossibility of inserting cannulae into pupilae Vateri or if due to the stenosis of the pancreatic duet in the pancreatic head instillation of the 27 contrast medium into the duet is not feasible. ­ In these cases attempts have to be made to find the part of the pancreatic duet accessible to the puncture line of the ultrasound appara­tus, and by means of UPP scan of the pancreatic duet, make a radiological image in different planes, and make a detailed analysis of it. Direct instillation of a contrast medium into the pancreatic duet yields very clear seans of the entire duet, its ramifications, places of stenosis and any accessory canals, at the same tirne providing important information on the passage of the contrast medium into the duodenum, or complete obstruction of the canal in the pan­creatic head_3-7 Examples of these seans of the pancreatic duet are shown in Figures 4, 5, 6, 7 and 8 while Figure 2. UPP -tip of the needle in the panereatie duet. Figure 1, 2 and 3 show the point of the needle in the pancreatic duet. Seans of the ductus pancreaticus by means of ultrasound guided percutaneous pancreato­graphy (UPP) are invaluable to patients suffer­ing from chronic steno-dilating pancreatitis, in preoperative planning of drainage procedures (pancreaticojejunostomy). 10 The patients are examined by two doctors and a medica! technician. The doctors must Ultrasound guided percutaneous pancreatography (UPP) Figure 4. UPP steno-dilated pancreatitis. have wide experience in interventional ultra­sound and interventional radiology. The 11 UPP-s described have been made under the control of ultrasound apparatus HI­TACHI EUB 410, with Convex probe of 3.5 MHz and lateral adapter for puncture. The needles used were Angiomed IPS 1.3 and SBK 0.95. By means of this method high-quality images of the pancreatic duet are obtained. Besides other findings they make possible differentia­tion between chronic pancreatitis and pancrea­tic carcinoma. The method is indicated in strictly limited cases. With an expert and skilled team it is carried out with ease. According to our expe­rience, so far the method has not been associa­ted with morbidity and mortality. We believe Figure 6. UPP steno-dilated pancreatitis. it will find application in highly developed and adequately equipped institutions dealing with the diagnostics and treatment of pancreatic complaints. References l. Rabinov KR, Simon M. Peroral cannulation of ampulla of Vater for direct cholangiography. Pre­liminary report of a new method. Radiology 1965; 85: 693-7. 2. Rubinic M, Švalba B. Endoskopska retrogradna holangiopankreatografija (ERHP). Radio! Jugosl 1984; 18: 95-8. 3. Copeberg PL, Cohen MM, Grahman M. Ultraso­nographically guided percutaneous pancreatogra­phy: "Report of two cases". AJR 1977; 132: 622. 4. Ohto T, Saotome N, Saicho N, Tsuchiya X, Ono T, Okuda K, Karasawa E. Real-Time Sonography_ of the pancreatic duet. Application to percutaneus Pancreatic ductography. AJR 1980; 134: 647. Ivani.;;: N et al. 5. Maruuchi M, Bandai X, !to I, Wada T. Ultraso­nically guided Percutaneus transhepatic cholangio­graphy and Percutaneus Pancreatography. Radio­logy 1980; 134 (3): 767. 6. Davcev P, Serafimovski V, Neškovski M, Bidikov V. Percutaneous transabdominal Real-Time sono­graphy of the Pancreatic duet. The third sympo­ sium of hepatology, Book of Abstracts. Ohrid, 1982. 7. Sutton D. A textbook of radiology an.d imagin.g. 1987: 1030. 8. Schwerk WB: Gastroen.terologische Ultraschall­ diagn.ostik in. Internist. 1981: 23. 9. Meckler U, Hennermann KH, Caspary WF. Ul­traschal des Abdomens. Koln: 1984. 10. Puestow Ch B, Gillesby WJ. Retrograde surgical drainage of pancreas for chronic relapsing pan­creatitis. AMA Arch Surg 1958; 76: 898. Radio/ Oncol 1992; 26: 125-9. Possibilities and limitations of computed tomography m diagnosis of thoracic organs Šerif Bešlic, F. Dalagija, A. Lovrincevic, M. Ibralic, Z. Merhemic University Medica! Center, Institute of Radiology and Oncology, Sarajevo, Bosnia and Hercegovina During a period of 6 years and based on own material and experience with 1012 examined patients, the authors have presented the contribution of computed tomography (CT). The examinations were performed on Somatom SF "Siemens" unit. According to the coded CT diagnoses stored at computer in the Department of lnformatics, CT showed the important contribution in the diagnosis of fluid, solid, cystic and jat formations in the chest. A considerable part of the findings, about 16.5 % related to the mediastinal and hilar adenopathies. The diagnostic role of CT in the analysis of vascular mediastinal structures is interesting. Key words: thoracic radiography; tomography; x-ray computed Introduction CT is a new, relatively expensive diagnostic method. It changed our previous practice and algorithm of diagnostic methods and enabled improved analysis of the mediastinum, Jung parenchyma, pleura and phrenico-costal sinus­es. Since the end of 1978, it has been performed at our Institute. On the basis of our clinic material and data from literature, we tried to present the pathology which can be proved by this method, as well as the problems related to this diagnostics. Correspondence to: dr. Šerif Bešlic, Institute of Radio­logy and Oncology, University Medica! Center, Moše Pijade 25, 71000 Sarajevo, Bosnia and Hercegovina. Material and method Clinical material From the end of 1986 to January 1, 1992, we investigated 1012 patients. Out of this number, the clinicians requested the examination in: 686 cases -CT of lungs, 227 cases -CT of mediastinum, 78 cases -CT of thorax, 28 cases -CT of other chest organs, 12 cases -CT of the heart etc. The analysis included patients of ali ages and both sexes. Method of work Since 1978, we have worked on the third gene­ration Somatom SF "Siemens" scanner with 512 detectors and 2.6 and 4.8 sec. scan tirne, 4 and 8 mm thick slices and immediate image UDC: 616.2-073.756.8 reconstruction. Density leve! is measured Bešlic š et a/. aeeording to Hounsfield: -1024 to + 1024 HU, where water is O. Eleetronie image enlargement is 2.5 times. The tube is pulsed superrotalix with graphite anode, eooled by oil. The image analysis has been performed at two levels, with the window for the analysis of mediastinum and eostal pleura in one, and for the analysis of parenehyma in another. Plain images were ob­tained in the first series, the seeond after in­fusion of water-soluble eontrast material ( 60 ml. i. v. in bolus and 100 ml in perfusion), for a better presentation of vaseular struetures. Rarely, a reinjeetion of eontrast material in the area of speeial interest was performed. After i. v. applieation of eontrast material fast mood seanning was performed in the following positions: deeubitus, lateral deeubitus and proeubitus. We applied eontrast material perorally ( esophagus). The thorax was investigated from the apex to the phrenieoeostal sinuses (20 seans). The suspeeted regions required additional seans with eontrast bolus. Seanning was made after eonventional radio­graphy with possible additions. The results were evaluated surgieally, by CT­guided transthoraeie biopsy, clinieally and by laboratory data. Results Out of the total number of examined patients CT findings showed as follows: The most of our CT diagnoses related to pleural exudations (25 % ) , mediastinal and hilar adenopathies (16.5 % ) , lung tumors (12.5 % ) , thymus diseases (2.47 % ), esophageal neo­plasms (1.97 % ), solitary metastases, infiltra­tions and eehinoeeoeal lung eysts (1.9 % ), fat deposits in mediastinum and retrosternal struma (1.48 % ) ete. In those eases, CT made the deeisive eontri­bution. Our results are presented on Tables 1 and 2, showing that besides the mentioned pathology, CT enabled the diagnosing of eysts and pulmonary abseesses, perieardial effusions diaphragmatie hernia, pleural tumors, traeheal Figure l. Echinococcus cyst left ( density leve! + 14 HU). neoplasms, eongenital vaseular malformations and aortie aneurysms. Discussion The analysed material shows that CT offers speeial possibilities in the analysis of all thoraeie struetures (ribs, spine, mediastinum, Jung pa­renehyma ete.) in the transversal plane. It is possible to analyse bony and museular struetures of the ehest (meta ehanges in ribs), with the advantage in the presentation of nor­mally radiotransparent struetures, as in lesions of the ehondrosternal joint ( abseess) .1-4 Compuled lomography in diagnosis of thoracic organs Transversal seans enable a good analysis of Jung parenchyma with confirmed solid, cystic 25 and liquid metastatic formations.1•·-10 (Figure 1,2). Our material includes mediastinal and hilar adenopathies in 16.5 % , solitary meta of the lungs (1-2 metastases) in 1.9 % , pulmonary tumors in 12.5 % , pulmonary cysts in 3.08 % ( out of that echinoccocal cysts in l. 9 % ) , whe­reas pleural effusions were diagnosed most fre­quently -in 25 % , in the total material. This shows the CT sensitivity which depends on the type of pathologic changes. In the changed anatomic relations in the thorax, CT improves the explanation of the conventional radiography, eliminating the su­perposition.1 · 2 CT enables a precise evaluation of the expan­sive process border, with possible analysis of its relation with the surrounding, especially vasculary structures.1•9• 11 It enables the evaluation of loco­regional (skin metastases) and metastatic expan­sion of the malignant process in the mediastinum, with good presentation of the retrosternal, retro­caval (Barety louge), subcarinal, back retrobron­chal, posteroinferior mediastinal space (sign "ice hi!!" Felson), azygoesophageal recessus and phre­ 2 1115 nicocostal sinuses.1 ·· ­ Our material includes: thymus pathology in 2.47 % retrosternal struma 1.48 % , esophageal neoplasms 1.97 % , fat collections in mediasti­ num 1.48 % , diaphragmatic hernia 0.39 % (Fi­gure 3). An adequate analysis of pleura and pleural cavity is possible.12 · 16 • 17 Pleural effusions are found in 25 % , and pleural tumors in 0.29 % of the total material. After intravenous application of contrast ma­terial, CT shows the vascular nature of tumo­rous formations in the mediastinum found by 18,19 conventional radiography . Aortic aneurysms were found in 6 cases (0.59 % ), and aberrant right subclavian artery in one case (Figure 4). It is also possible to check the graft and endarterectomized vascular segment, and to analyse the pericard and heart, as well as to measure heart dimensions.18· 20 Pericardial ex­udations were presented in 0.49 % of the cases. The scanner enables a supreme visualization of calcifications, invisible by the conventional radiography. 1 ·18 In some cases CT is suggestive of the tumor _ type histology (fat, liquid, vascular, convolute 12-1418 etc. ). 2·9 • ·It simplifies the diagnostic pro­cedures by making some investigations op­tional ( angiography, tomography, endosco­ 1 , 13 ,14 ,18 ,19 PY) _ CT helps the surgeon in the selection of surgical approach and technique, and offers additional possibility of the therapeutic follow- Bešlic š et al. Table l. Distribution of positive and normal CT findings No of positive CT findings 731 72.2% Normal CT findings 281 27.8% Total 1012 100.0% Table 2. Distribution of positive CT findings by diag­ noses No. of Percen­ 0rdinal CT diagnosis examined tage nurneral patients % l Pleural effusions 253 25 2 Mediastinal and hilar adenopathies 167 16.5 3 Pulmonary tumors 127 12.5 4 Thymoma and thymus hyperplasia 25 2.47 5 Esophageal neoplasms 20 14 Aortic aneu1ysm 6 0.59 15 Pericardial exudation 5 0.49 16 Diaphragmatic hernia 4 0.39 17 Pleural tumor 3 0.49 18 Tracheal neoplasms 1 0.098 19 Aortic dextroposition 1 0.098 20 Aberrant right subclavian a1te1y 1 0.098 21 Cystic teratoma 0.098 Total 731 72.2 up.1• 11 Transthoracic biopsy is also performed 2 under the guidance of CT.1· Diagnostic limitations Besides various advantages, CT fails to define the pathologic nature of the lesion (benign or malignant), but enables the prediction of this possibility (lypoma, cyst, Jung sequestra­ 613 l4 19 tion)1····CT is unable to define the struc­tures (lymphnodes) or diffuse infiltrations of organs (!iver, spleen).1 • 12 It is difficult to differentiate tumors from the near adenopathies (skin metastasis).1 • 11 The evaluation of bacillosis, pneumoconiosis or pul­monary infarction is stili performed by the conventional radiography, whereas analysis by CT has been discussed (the expensiveness of CT).1 During its first phase prehernial lypoma can be misinterpreted for intrathoracic fat collec­tions.14 It is impossible to differentiate between 16 17 a primary and a secondary pleural tumor.9·, There is a possibility of false positive and false negative results (cervical lymphnode con­sidered as parathyroid adenoma; undetected tuberculoma and metastasis under 1 cm of size, due to the Jack of axial cross-section.1 There are limitations of the technical nature (impossibility of apnea, thin patients and child­ren, metallic protheses, partial vol ume effect etc.) which can change the image quality and 6 Solitaiy meta of the lung (1 to 2) 19 densitometric values.1•5• 18 7 Pulmona1y infiltration 19 1.9 8 Pulmona1y echinoccocosis 19 9 Fat deposits in mediastinum 15 1.48 10 Retrosternal struma 15 1.48 Conclusion 11 Pulmona1y cysts 12 1.18 12 Pulmona1y tuberculosis 11 1.08 CT is a 11011-invasive technique indispensable in Pulmonary abscess 7 0.69 the modem diagnostics. It is frequently the method of choice in the diagnosis of pulmonary and mediastinal diseases, especially in the re­gions traditionally inaccessible by the conven­tional radiography. It simplifies the diagnostic procedure ( excluding the angiographies and to­mographies). Without CT, diagnostics becomes more complex, which is the best defence for this technique. CT does not replace conventional radio­graphy or other techniques, but it is comple­mentary. References l. Treut A, Guibert JL, Dilhuydy MH. Les bonnes indications de la tomodensitometrie en cancerolo­gie. Rev Prat 1987; 37 (36): 2153. 2. Chalaoui J, Barral V, Simard P, Lefebvre R, Sylvestre J. Mesotheliome pleural: trois forms evolutives. Ann Radio! 1982; 25 (3): 191--4. 3. Prija J, Larde D, Katz M, Yasile N, Vadrot D, Utzmann O. Le diagnostic tomodensitometrique des anomalies des arcs chez l'adulte. J Radio/ 1982; 63 (3): 159-65. Computed tomography in diagnosis of thoracic organs 4. Smoger BR, Rosenberg HK, Koss J, et al. La recherche de metastases pulmonaires en pediatrie: la tomodensitometrie face aux techniques radiolo­giques conventionnelles. Ann Radio/ 1982; 25 (1): 47-53. 5. Spiro S, Edwards D, Harper PG, et. al. Computed tomography of the thorax in the diagnosis and management of malignant disease. Br J Dis Ches 1982; 76 (3): 209-22. 6. Belloir C, Larde D, Vasile N, Frija J, Ferrane J. Apport de la tomodensitometrie dans le diagnostic et le bilan des anevrysmes de !'aorte. l. Radio/ 1980; 61 (8-9): 521-6. 7. Frija J, Abadie E, Fisch A, et al. Le diagnostic des hematomes de la parni du tronc par la tomo­densitometrie. Ann Radio/ 1982; 25 (8): 528-31. 8. Kalifa G, Lalande G, Larde D, Bennet J, Kalifa C. Les fibromes desmoides chez l'enfant. Ann Radio! 1982; 25 (1): 25-33. 9. Collard M, Brasseur P, Sukkarieh F. Les indica­tions et les limites de la tomodensitometrie thora­cique. Ann Radio/ 1980; 23 (8): 629-38. 10. Tschappeler H, Yock P. Computed tomography and bone tumors in children. Ann Radio! 1982; 25 (1): 19-24. 11. Browu RL, Muhm JR. Computed Tomography of the Thorax Current Perspectives. Chest 1983; 83 (5): 806-8. 12. Tschappeler H. Computed tomography (CT) and lymphoma in children. Ann Radio/ 1980; 23 (2): 87-91. 13. Caron-Poitreau C, Mainchain HN, Rieux D, Vialle M, Caron J. Examen Tomodensitometrique des piliers du diaphragme. Apport a !'etude du mediastin postero-inferieur . .! Radiol 1980; 61 (1): 1-11. 14. Caron-Poitreau C, Delumeau J, Dabouis G, Peti­tier H, Rieux D. Apport de la Tomodensitometrie a !'etude des tumeurs primitives de la plevre. Ann Radio! 1981; 24 (4): 247-53. 15. Frija J. Princips de la tomodensitometrie. Rev Prat 1987; 7: 30. 16. Coulomb M, Terraube Ph, Vincent J, Lebas JF. Les arnas graisseux du mecliastin. Apropos de 21 abservations, dont 16 avec tornodensitornetrie . .l Radio/ 1980; 61 (1): 13-26. 17. Coulomb M, Terraube Ph, Lebas JF, Chouteau H, Geiudre M. Amas graisseux intra-thoraciques symptomatiques d'une hernie diaphragmatique chez l'adulte. A propos de 11 observations avec etude tomodensitometrique . .! Radio/ 1981; 62 (2): 85-95. 18. Coulomb M, Spinelli G, Lebas JF, Terraube Ph, Sarrazin R, Geinclre M. Apport de la tomodensi­tometrie au diagnostic des kystes derrnoides. A propos de 5 observations. J Radiol 1982; 63 (12): 729-37. 19. Coulomb M, Lebas JF, Sarrazin R, Geindre M. L'apport de la tomodensitometrie au bilan d'ex­tension des cancers de l'oesophage. Incidences therapeutiques. A propos de 40 observations . ./ Radio/ 1981; 62 (10): 475-87. Radio! Oncol 1992: 26: 130-9. Clinical advances of contrast-enhanced MR imaging A review Vinko Kristl Institute far Diagnostic and lnterventional Radiology, University Clinical Centre, Ljubljana Slovenia The review shows clinical use and some results obtained with contrast agent gadopentetate dimeglu­mine (Gd-DTPA). It may improve the diagnostic capability of MR imaging. The contrast-enhanced MR imaging is relatively new diagnostic modality and has rapidly evolved from an experimental field to a widely used clinical technique. Further studies are needed to confirm most of potential indications. Key words: magnetic resonance imaging; gadolinium; gadolinium-DTPA, diagnostic approach. Introduction differentiating lesions such as neoplasms or In a relatively short tirne, MR imaging became an essential diagnostic tool for the practice of medicine. Tissue relaxation times (T1, T2), pro­ton density and flow are the principal intrinsic factors, that determine signal intensity on MR images. During the early development of MR imaging there was no exogenously administered contrast material. Anatomic regions that can be immobilized, such as the head, spine and extre­mities present few obstacles to MR imaging. Routine technique produces excellent images of these regions. MR images of the body, on the other hand, have suffered from low spatial resolution, low signal -to -noise rations and motion -related artifacts. With greater clinical use of MR imaging, however, the difficulty in Correspondence to: Vinko Kristl, MD, IDIR, Univer­sity Clinical Center, Zaloška 7, 61000 Ljubljana, Slo­venia. UDC: 539.143.43 abscesses of the central nervous system and other organs from surrounding edema became apparent. Intensive efforts to improve the diag­nostic utility of body MR imaging have resulted in a variety of specialized approaches: pharma­ceutical manipulation of signal-to-noise ra­tions, tissue contrast improved data acquisition, and image processing. Contrast agents alter the tissue signal intensity by either decreasing pro­ton relaxation times or by altering proton den­sity. Now it is known that MR contrast agents improve the usefulness of MR imaging which plays an increasingly important role in clinical practice. Contrast -enhanced MR imaging can simultaneously provide dynamic physiologic in­formation (anatomic and/or biochemical) and high anatomic detail, thereby overcoming the major limitations of both nuclear scintigraphy (poor anatomic resolution) and CT (limited physiologic information). 1 Thus, in both physio­logic and pathologic situations where contrast enhancement is seen with CT, a similar result should be expected with MR imaging. There Clinical ac/va11ces of con1ras1-enhancec/ M R imaging are major differences with MR imaging depen­ding on the pulse sequence used. T 1 dependent pulse sequences show the greatest enhancement and T2 dependent pulse sequences show the least enhancement. Differences in CT and MR imaging are also in display of calcified tissue, flow effects. 1 • 2 Gadolinium diethylene triamine pentaacetic acid in form dimeglumine salt (Gd-DTPA) is the first MR contrast agent which received Food and Drug Administration approval in June 1988, and is used in clinical practice. Gd-chelated to DTP A molecules make up a contrast agent which has no tissue specificity. Metal ion is chelated to reduce biologic toxicity, biodistribution and pharmacokinetics are li­gands dependent. Toxicologically Gd-DTP A is similar to a common iodinated contrast agent. Pharmacology of Gd-DTPA After i. v. injection, Gd-DTPA has a plasma half-life of 90 min. This biodistribution follows a two compartment model. It is rapidly redistri­buted from the vascular compartment into the extracellular space and undergoes renal elimina­tion by passives glomerular filtration. 1 The kid­neys concentrate Gd-DTP A and over 90 % of it is excreted unchanged with urine within 3 hours. A very small amount of it is excreted through the gastrointestinal tract. Gd-DTP A does not cross the normal blood-brain barrier. Gd-DTPA produces changes in tissue T1 and T2. There is no direct relationship between the concentration of Gd-DTP A and the observed signal intensity. Toxicity of Gd-DTPA Immediate short-time side effects have not represented a problem; for example blood pres­sure and pulse rate have been stable. There are some increased or decreased values in some parameters noted in hematologic testing. There is 15 -30 % incidence of transient increase in serum iron concentration. This bas generally persisted for less than 24 hours and has returned to normal. A transient rise in serum bilirubin has also been observed in a few cases, although no significant clinical sequelae developed. No evidence of in vivo dissociation of the Gd­DTP A complex exists, and further trials have been planned on the assumption that these side 34 effects are not of major clinical importance. 1• , Gd-DTPA ejfects on T1 and T2 Gd-DTP A produces a change in ralaxation rates, which are reciprocal of T 1 or T2 relaxation time. Increasing of Gd-DTPA concentration produces a decrease in both T1 and T2 . This reduction will be greater in absolute terms for T 1 than for T2. Protons within fat are not as accessible to Gd-DTP A as protons in free water, thus the changes to protons in fat would be expected to be less than those for protons in water. The term "negative enhancement" is used to describe the situation where tissue signal intensity is decreased by a contrast agent. By using Gd-DTP A, a great change in signal intensity is seen in the inversion recovery se­quence (IR). The overall effect of Gd-DTP A depends on the dosage of contast agent. Dosages of 0.1 ­ 0.2 mmol/kg body weight are used. Delayed examinations of the brain may show a greater effect than immediate examinations because transport of Gd-DTP A across the blood-brain barrier may take tirne. The reverse may be true with very vascular lesions. It must also be remembered that although many pathologic processes increase T1 and T2, Gd-DTPA de­creases T1 and T2. Thus considerable potential exists for "isointense" behaviour, whereby the contrast agent reduces tissue T1 and T2 values back to those of the adjecent normal tissue, producing a net loss of tissue conspicuity. Clinical studies investigating the use of con­trast agent in MR imaging of the body are few in comparison to studies of contrast -enhanced MR imaging of the brain and spina! canal. 1 This fact is attributable in part to the relatively greater complexity associated with contrast-en­hanced MR imaging of non-neurologic disor­ders. For example, Gd-DTPA induced signal enhancement can result in more pronounced 132 Kris1/ V motion artifacts, and the rapid diffusion of contrast into the extracellular space may neutra­lize soft-tissue contrast between healthy and diseased tissues. From this point of view it is sensible to presenet separately neurologic and non neurologic applications of Gd-DTP A in MR imaging. I. Neurologic Gd-DTP A applications Gd-DTP A does not cross the normal blood­brain barrier but is present in higher concentra­tion in the gray matter as compared with the white matter, reflecting the different vascularity of these tissues. Owing to differences in perfu­sion, the gray matter will enhance more than the white matter, resulting in a loss of gray­white soft tissue contrast on postcontrast ima­ges. The pituitary stalls, pituitary gland, caver­nous sinus and choroid plexus enchance also. Because of flow, vascular enhancement is more variable than it is with CT and is most obvious in the structures. During spina! imaging the normal cord, nerve roots, and intervertebral disks do not enhance.2 The blood-brain barrier is generally imper­meable to Gd-DTP A. In a variety of patholo­gical conditions including tumors, infections and demyelinating diseases it becomes permeable (vascular permeability), and Gd-DTPA accu­mulates in an extravascular location. For scree­ning examination of the brain highly T2 weig­hted spin echo (SE) sequences (these are insen­sitive to contrast enhancement) and T1 weighted sequence (either IR or SE) are used for better anatomic details. T1 weighted sequences are sensitive to contrast enhancement. Benign tumors Meningioma exhibits an increase in T1 and T2 (Figure 1).5 Some meningiomas display only a slight increase in T1 as compared with the white matter, and have T2 values within the normal range for the brain. Calcifications and bony changes are poorly shown by MR imaging. It is possible to predict meningioma (histologic a b Figure l. Meningioma without contrast agent: a -SE 2800/30, b -SE 600/20, Gd-DTPA enhanced. subtypes) on signal intensity (SI) changes5 . Gd­DTP A is most useful in the detection and characterization of small meningiomas. In a case of meningioangiomatosis (rare cor­tical hamartomatous Iesion) Gd-DTPA can show no lesion enhancement, which suggests an intact blood-brain barrier.6 Acoustic neuroma shows an increase in T1 and T2 . It is located within the interna! auditory canal, within the cerebellar pontine angle or within the posterior cranial fossa. With larger tumors contrast between the brain and cerebral edema is important. Sequences of T1 and T2 weighting are used. Contrast enhancement is of great value. Extravasation of the contrast agent molecules through the blood-brain barrier into a brain lesion results in a focal contrast enhan­cement. Characteristic tirne dependent contrast enhancement of cerebral lesions is helpful in differentiation between meningiomas and neuri­nomas. 7 MR imaging with Gd-DTP A enhancement is the preferred method for depicting intracanali­cular acoustic or facial neuromas, but enhance­ment of the nerve, even focal enhancement, is not diagnostic for the neuroma (nonneoplastic Jesions, and neuritis may mimic a small acoustic neuroma on MR imaging). 8 Other benign tumors Enhancement has been seen with pituitary tu­mors, chordomas, glomus jugular tumors, and epidermoid tumors. C!inical advances of contrast-enhanced M R imaging Malignant tumors It is difficult to separate edema from tumor because both processes produce an increase in T 1 and T2 . Differences between them depend only on exploiting relative differences in the degree of these changes. With more imaging sequences, there is more chance to separate the tumor from edema. Highly malignant tumors show greatest enhancement with Gd-DTP A contrast. Enhancement within cystic tumors has a\so been seen. Sometimes enhancement of areas of apparent edema can be seen with Gd-DTP A where it probably represents tumor infiltration.2 Enhancement on MR imaging may be espe­cially valuable in low grade tumors and may be an important guide to biopsy when no enhance­ment is seen on CT. With noncontrast imaging using a selection of T1 and T2 weighted pulse sequences it is not possible to obtain the same separation level of tumor from edema achieved with Gd-DTP A. So is Gd-DTP A helpful in identifying the nidus of tumor, and contrast agent clearly improves the diagnostic sensitivity of T1 weighted pulse sequences. It is important to remember that Gd-DTP A enhancement does not delineate the borders of tumors, but rather the side of maximal blood-brain barrier breakdown. Gd-DTPA should be used for scan­ning tumors of the fronta!, ethmoid, and sphe­noid sinuses for the evaluation of intracranial spread extension of disease. Reactive edema in the inferior fronta! ]obes can be seen. 9 Mild focal or diffuse dura] enhancement with Gd­DTP A is a normal finding on enhanced MR imaging in the pediatric patient who bas under­gone biopsy, craniotomy or intraventricular shunt placement for an intracranial neoplasm or associated hydrocephalus.10 Gd-DTP A enhanced examination is very use­ ful in patients with metastatic disease, where it is possible to identify more lesions. After cere­ bral tumor resection, enhancement of residual or recurrent tumor is readily separated from postoperative changes such as encephalomala­ cia or gliosis. The value of Gd-DTP A in sepa­ rating radiation necrosis from a residual tumor is unclear. 2 Cerebrovascular diseases With the use of contrast agent in MR imaging luxory perfusion is noted in the cases of cerebral infarction. Contrast agent is of diagnostic value in differentiating subacute from chronic cere­bral infarctions to predict the age of the lesion. Most of the subacute lesions showed the signs of mass effect (increased blood flow represents a luxury perfusion due to collateral formation or reopening of occluded vessels) (Figure 2).11 Furthermore, Gd-DTPA appers to be useful in the MR evaluation of early ishemia and its response to intervention.12 Arteriovenous malformations show a diffe­rent pattern. Slowly flowing blood has great enhancement and rapidly flowing blood has no enhancement. The type of venous drainage, either superficial or deep, could be determined by contrast enhanced MR imaging. The intrave­nous administration of contrast adds significant information in the MR study of venous angio­ma.13 Ring enhancement in contrast MR imaging has been identified at the margin of giant aneurysms (probably reflecting proliferation of the vasa vasorum). Enhancement of the membrane associated with subdural hematomas may be visualised. 134 Kristl Demyelinating diseases Multiple sclerosis was the first disease in which MR imaging was demonstrated to have signifi­cant advantages over X-ray and CT. Multiple sclerosis is the major indication for MR imag­ing. lts sensitivity is increased by the use of Gd-DTPA and by delayed examination.2 Non­contrast MR imaging is very sensitive in detec­ting demyelinating diseases, especially on T2­weighted images. 14 However, gadopentetate dimeglumine enhan­ced MR has been shown to be more sensitive than contrast enhanced CT for identifying re­gions of abnormal blood-brain barrier that may correlate with clinical activity. In patients with chronic partial epilepsy Gd­DTP A should be used selectively to clarify or better define the nature of abnormalities en­countered on unenhanced seans. The likelihood of missing an important abnormality by per­forming unenhanced imaging alone is sma!!. 15 Infections Ring enhancement is a well known feature of cerebral abscess and other patterns of enhance­ -ment may a!so be seen both with abscess and other forms of CNS ( central nervous system) infections. MR has been demonstrated to be sensitive for the detection of CNS involvement with vira! infections. In case of acute dissemina­ted encephalomyelitis MR typically demonstra­tes multiple focal areas of increased signal on T2 weighted images within the brain stem, cerebrum and cerebellum. Predominant patho­logic finding with this disorder are focal areas of demyelinization. MR abnormalities are typi­cally Jocated within the white matter. 16 In a case of parasitic desease (neurocysticer­cosis) contrast enhancement around the cysti­cerci seems to occur when there are both sur­rounding edema and signal intensity of the cyst contents higher than cerebrospinal fluid on T1 and proton density-weighted images. Such en­hancement probably reflects degeneration of the worms and an inflammatory reaction of the adjacent brain tissue. The degree of contrast V enhancement on MR imaging may indicate the degree of focal parenchymal inflammatory reac­tion around the cysts. 17 Orbit The advantages of MR imaging in this site are as follows: there radiation on the lens, high soft-tissue contrast visualizing of the optic nerve within the optic canal. The abundant orbita! fat leads to chemical shift misregistration artefacts. In the cases of optic neuritis, the abnormally enhanced nerve is often masked by the surrounding high signal fat on T 1 weighted images. Post Gd-DTPA fat suppresion T1 weig­hted images clearly identified the shaggy, en­hanced inflammatory perioptic lesions with or 18 without an enhanced optic nerve. With this finding we can differentiate perineuritis from the smoothly outlined enhancing perioptic me­ningioma. Soft tissues, nasopharynx and soft tissue of the neck We can see differential enhancement between the lesion and normal mucosa. Mucosa has high leve! of vascularity and high water content so it displays a moderately high leve! of enhance­ ment with Gd-DTP A. Gd-enhanced MR ima­ ging of the cranial nerves (fifth nerve) is recom­ mended in patients with cranial nerve sensory or motor deficit or neuralgia. Contrast enhanc­ ed MR imaging appears to be superior to noncontrast imaging, as it is possible by means of imaging characteristics, to separate benign from malignant disease. 19 Spinal cord With MR imaging it is possible to visualize the spina! cord directly without intrathecal contrast agents. Parenchymal changes within the cord can also be seen directly. Gd-DTP A is used for defining extramedullary lesions and for dis­tinguishing tumor from edema, and defining the extent of metastatic spread. It is possible to differentiate scar from a recurrent disk Clinical advances of' contrast-enhanced M R imaging following surgery. Overall, the spina! cord has been one of the most promising sites for the use of Gd-DTP A. Three dimensional gradient echo steady state sequence and postprocessing gives a view of the thecal sac and the dura! root sleeves.20 It may provide enough informa­tion to eliminate the need for contrast myelo­graphy in the evaluation of extradural disease. Gd-DTP A provides conspicuity of tumors, in­flammatory and infective processes. It anables differentiation of cystic tumors from syringo­myelia and post-radiation cord damage, and epidural fibrosis from recurrent disc. II. Non-neurologic applications Thorax Flow properties of MR imaging enable differen­tiation between masses and vascular structures. The indications for Gd-DTP A in MR imaging might be expected to be fewer than the indica­tions for iodine based agents in CT. Mediastinal masses have displayed enhancement and the pattern of the proximal pulmonary vasculature can be demonstrated with them. Contrast enhacement has been seen in the margin of areas of myocardial infarction. There are two or three zones identified in acute, subacute or chronic stages of myocardial infarc­tion. Greater enhancement is produced in the peri-infarction zone than in the normal or infar­ 22 cted myocardium.21, By diagnostic MR it is possible to determine pseudoaneurysms of the heart.23 MR can detects intramural and intraca­vitary cardiac tumors which are bigger than 5 mm. MR imaging can also provide essential information on tumor extent, location, and relation to the cardiac and paracardiac structu­res. 24 Gd-DTP A has proved valuable in separating neoplastic from fibrotic lesions within the breast, although difficulties in distinguishing benign and malignant tumors remain. In the case of bronchus tumor or mesothelioma the major use of MR is in the evaluation of media­stinal involvement, the relationship of the tu­mor to the great vessels, and the presence of chest wall involvement. 25 MR imaging is similar to CT in its ability to evaluate normal and abnormal hila and mediastina.26 MR is superior to CT in showing enlarged hilar lymph nodes, but CT is better for demonstrating bronchial abnormalities. 27 Because of the contrast resolution between static and flowing blood, pulmonary emboli can be demonstrated non-invasively, but the que­stion remains whether the increased signal in­tensity depends only on slow flow or on the embolus itself. 28 The central vasculature in the mediastinum can be evaluated by means of MR angiography. Two dimensional FLASH angiography (a fast low angle shot two-dimensional pulse sequen­ce) can be postprocessed into a three-dimensio­nal MR angiography by a maximum intensity projection algorithm.29 Alterations in both T 1 and T 2 reflect changes in water content of inflammatory alveolitis to fibrotic lungs.30 Abdomen Liver: The normal !iver parenchyma shows mar­ked enhancement soon after an intravenous injection of Gd-DTP A but this decreases with its redistribution and excretion. The !iver, pan­creas, and adrenal gland enhance homogeneou­sly, whereas the spleen, kidney and the abdomi­nal aorta and inferior vena cava enhance hete­rogenously with dynamic gadolinium-enhanced MR imaging. 31 Liver tumors show variable enhancement but may also have greater enhancement than nor­mal !iver so that they become isointense (Figure 3). Gd-DTPA enables better differentiation between necrotic and other areas of tumor, more precision in defining tumors and differen­tiation between portal veins and dilated bile ducts. MR correctly localized 90 % of the !iver metastatic lesions. MR represents an ideal mo­dality for lesion localization because it accure­tely depicts hepatic vessels fissures that define segmenta! boudaris. The flow void phenomenon causes the hepatic veins to be strikingly low in 136 Kristl V signal. Because the hepatic veins act to separate the hepatic segments, lesion site can be easily assessed. 32 The appearance of hemangiomas in dynamic gadopentetate dimeglumine enhanced MR imaging is characterized by hyperintense perip­herial enhancement followed by a fill-in pheno­menon. This is quite distinct from the enhance­ment behaviour of !iver metastases, and hepato­cellular carcinomas. The difference in SI bet­ween hemangiomas and metastases is most stri­king on delayed images. Hypervascular meta­stases do not show the homogenous high SI typical of hemangiomas. Focal-nodular hyper­plasia is characterized in dynamic contrast-en­hanced MR imaging by a strong contrast enhan­cement with a peak during the first 30 seconds after contrast administration, and by a rapid decrease in SI. 1 Turbo FLASH (fast low angle shot) dynamic scanning of !iver with Gd-DTPA enhancement significantly improves lesion-liver contrast particularly in the cases of focal nodu­lar hyperplasia of the liver.33 Improved !iver-to lesion contrast is possible with intraarterial por­tography with Gd-DTPA.34 Spleen: The sensitivity of MR imaging in the detection of tumorous lesions of the spleen is low because relaxation times and SI of normal spleen and intraspleenic tumors are very simi­lar. Contrast agents can dramatically improve tumor detection. Normal spleenic enhancement pattern during dynamic gadolinium-enhanced T1 weighted spin-echo MR imaging is heteroge­neous, with conversion to homogeneous enhan­cement one minute later.35 Prolonged enhance­ment on postcontrast MR imaging is a useful finding in differentiation of spleenic hamartoma (rare benign lesion) from malignant lesions of the spleen ( especially from nodular lesions af malignant · lymphoma). 36 Pancreas: In evaluating diseases of the pan­creas, MR is stili inferior to CT. Development of oral contrast agents is a first step toward improving the usefulness of MR imaging of the pancreas, because the pancreas must be first differentiated from the gastrointestinal tract. In cases of pancreatic transplant dysfunction Gd­DTP A enhanced MR imaging is a very sensitive technique. 37 Adrenals: Malignant tumors and pheochromo­cytomas show a significantly greater SI than adenomas in precontrast images. After admini­stration of Gd-DTP A only moderate enhance­ment and quick washout is observed in adeno­mas, whereas malignant tumors and pheochro­mocytomas show strong enhancement and slo­wer washout. 1 With gradient echo sequences adrenocortical adenomas display a lower SI than other adrenal lesions on T2 weighted ima- Figure 3. Hepatocelullar carcinoma a -short TRITE (700/20) SE sequence, b -short TRITE (700/20) SE seguence after Gd-DTPA injection. C/inical advances of co11trast-enlwnced M R imaging ges. Pheochromocytomas, metastases, and car­cinomas of the adrenals show a high SI. Addi­tional dynamic contrast enhanced studies allow further classification. The physiopathologic mechanism of different enhancement patterns is based on the strong perfusion of malignant tumors. A disturbed penneability of the capilla­ries of malignant lesions leads to an increased diffusion of the contrast agent into the intersti­tial space. In the case of metastases and carci­nomas, the contrast agent is retained in the extravascular space for a longer period of ti­me. 38 Additional advantage of MR images is that multiplanar sections allow a better over­view of the topographic relationships. Kidney: In the kidney Gd-DTPA is concentra­ted and sharp differentiation between the cortex and medula can be produced. The concentra­tion of Gd-DTP A in the collecting system is usually sufficient for reduction in the T2 of urine to dominate the reduction in T1 producing a zero signal with ali sequences using the con­ventional doses. If a low dose is given and the patient is scanned quickly, however, an increa­sed SI may be seen in the collecting system. Contrast-enhanced MR imaging for both tumor diagnosis and functional assessment is best achi­ved when dynamic studies are performed in combination with a bolus injection of gadopen­tetate dimeglumine. Gadolinium-enhanced MR imaging is an effective method for characteri­zing renal lesions in patients with renal insuffi­ciency. At the usual dosage there appears to be no nephrotoxic reaction in these patients.39 Retroperitoneum: A variety of retroperitoneal lesions have displayed enhancement which may produce a better deffinition of the extent of particular lesions. MR imaging bas proved un­reliable in the distinction of normal and neopla­stic nodes by means of SI characteristics, be­cause the relaxation times and proton densities 1 of normal and metastatic nodes overlap. Pelvis: General considerations applicable to imaging of soft tissue outside the CNS apply to the pelvis. Pelvic tumors display enhancement and similar parallels have been seen with other pathologic processes. The bladder shows con­centration phenomena, whereby a signal from the posterior bladder (concentrated Gd-DTPA) may be zero with a zone of enhancement bet­ween lower and upper zones where the concen­tration is optimal with essentilly normal urine above. Contrast-enhanced MR imaging appears to allow better bladder tumor staging than do precontrast T1 and/or T2 weighted pulse sequen­ces. This is especially trne for the distinction of superficial tumors from those infiltrating the muscle, because noninvolvement of the muscle layer is visualized as an intact hypointense line in the region underlying the tumor. The applica­tion of Gd-DTPA proved valuable in detecting small bladder tumors and in differentiating bet­ween necrotic and vita] tissue within large ones. Tumors are generally characterized by a very inhomogeneous perfusion with an augmented vascularization along the edges of the tumor and a rarified capillary network within the tumor center. This probably causes an U11even distribution of contrast medium within bladder tumors. Neurofibromas show a markedly in­creased SI on T2 weighted images relative to the surrounding soft tissues with marked enhan­cement following Gd-DTP A administra­tion.40,41 Reports of MR imaging for staging of bladder neoplasms have been encouraging owing to its inherent soft tissue contrast as well as the advantage of multiplanar applicability. How­ever, some authors suggest that the accuracy of MR imaging performed without a contrast me­dium in determining the depth of tumor inva­sion is only slightly better or even worse than that of CT.42 However, both precontrast and postcontrast T1 weighted images of the bladder should be obtained. In the diagnosis of tumors of the uterus, Gd-DTP A enhanced MR imaging can yield additional information in patients with endome­trical carcinoma. Viable and necrotic areas are easier to distinguish on postcontrast than on T2 weighted precontrast images. In the evaluation of ovarian masses, Gd-DTPA improves the 138 Kristl V visualization of the tumor structure and may al1ow better distinction of inflammatory adnexal processes from malignant tumors. 1 M uscle-skeletal system Contrast enhanced MR imaging with T1 weight­ed echo pulse sequences is more variable in distinguishing different tumor components, ne­crosis, peritumoral edema and viable tumor tissue, than is precontrast imaging. Marked improvement occurs after contrast application compared with the T1 weighted precontrast image, the contrast is never as strong as in T2 weighted precontrast sequences. Application of Gd-DTP A reduces the contrast between enhancing tumor and signal-intensive fatty tis­sue and bone marrow. This is used for charac­terization and evaluation of tumors before and 43 after treatment.Gd-DTPA MR imaging is used also in the joints for delineation of carti­lage and tendon tears, for differentiation bet­ween pannus and joint effusion and for the delineation of infection processes.44 Conclusion Administration of Gd-DTP A has pointed out that MR imaging in no longer nonivasive in the strict sense, and the duration of the examina­tions may be increased. Once Gd-DTPA has been accepted, the question concerning its strict clinical indications needs to be solved. As with other aspects of MR imaging, the options are wide, and the principal agent in use at the present tirne, Gd-DTP A is one of the most obvious choices. Much more effort will undoub­telly be expended on developing other contrast agents, some of which will find application in clinical practice. Without a gastrointestinal con­trast agent, MR imaging wil1 be unable to provide globa! examination of the abdomen. With novel formulations such as the nonionic isoosmolar preparations, higher doses or pro­longed infusion may further improve diagnostic information. References l. Saini S, Modic MT, Hamm B, Hahn PF. Advances in contrast-enhanced MR imaging. AJR 1991; 156: 235-54. 2. Stark DD, Bradley WG. Magnetic resonance imag­ing. St. Louis: The C. V. Mosby Company, 1988. 3. Kristl V. Contrast agents in MR imaging. Radio/ !ugasi 1991; 25: 355-9. 4. Laniado M, Claussen C, Weinmann HJ, Schroeder W. Paramagnetic contrast media in magnetic reso­nance imaging of the brain. In: Taveras JM, Ferrucci JT. Radiology. Lippincott, Philadelphia. Vol. 3, part 59, 1989. 5. Kaplan RD, Coons S, Drayer BP, Roger Bird C, Johnson PC. MR characteristics of meningioma subtypes at 1.5 tesla. J Comput Assist Tomogr 1992; 16: 366-71. 6. Tien RD, Osumi A, Oakes JW, Madden JF, Burger PC. Meningioangiomatosis: CT and MR findings. J Comput Assist Tomogr 1992; 16: 361-5. 7. Felix R, Schoerner W, Sander B, et al. Contrast­enhanced MR brain studies: clinical experience with Gd-DTPA over four years. Diagnostic lmag­ing 1988; Supl. 13-5. 8. Han MH, Jabour BA, Andrews JC at ali. Nonneo­plastic enhancing lesions mimicking intracanalicu­lar acoustic neuroma on gadolinium-enhanced MR images. Radiology 1991; 179: 795--{5. 9. Tasse! P, Ya-Yen Lee. Gd-DTPA enhanced MR for detecting intracranial extension of sinonasal malignancies. J Comput Assist Tomogr 1991; 15: 387-92. 10. Hudgins AP, Davis PC, Hoffman JC. Gadopent­etate dimeglumine enhanced MR imaging in chil­dren following surgery for brain tumor: spectrum of meningeal findings. AJR 1991; 156: 1237-43. 11. Cordes M, Henkes H, Roli D, Eichstaedt H, Christe W, Langer M, Felix R. Subacute and chronic cerebral infarction: SPECT and Gadoli­nium-DTPA enhanced MR imaging. J Comput Assist Tomogr 1989; 13: 567-71. 12. Crain Mr, Yuh WTC, Greene GM, Loes DJ, Ryals TJ, Sato Y, Hart MN. Cerebral ischemia: evaluation with contrast-enhanced MR imaging. 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J Comput Assist Tomogr 1991; 15: 223-7. 19. Sevick RJ, Dillon WP, Engstrom J, Bergman WG, Ric Harnsberg H. Trigeminal neuropathy: Gd-DTP enhanced MR imaging. J Comput Assist Tomogr 1991; 15: 605-11. 20. VanDyke CW, Modic MT, Beale SM, Amartur S, Ross JS. 3D MR myelography. J Comput Assist Tomogr 1992; 16: 497-500. 21. Saeed M, Wendland MF, Masui T, Connolly AJ, Derugin N, Brash RC? Higgins CB. Myocardial infarction: assessment with an intravascular MR contrast medium. Radiology 1991; 180: 153-60. 22. van Dijkman PRM, van der Wall EE, de Roos A, Matheijssen NAA, van Rossum AC, Doornbos J, van der Laarse A, van Voorthuisen AE, Brusch­ke AVG. Acute, subacute and chronic myocardial infarction: quantitative analysis of gadolinium-en­hanced MR images. Radiology 1991; 180: 147­150. 23. Duvernoy O, Wikstrom G, Mannting F, Larson SG, Andren B, Dubiel T. Pre-and postoperative CT and MR in pseudoaneurysms of the heart. J Comput Assist Tomogr 1992; 16: 401-9. 24. Rienmueller R, Lloret JL, Tiling R, Grah J, Manert W, Mueller DK, Seifert K. MR imaging of pediatric cardiac tumors previously diagnosed by echocardiography. .1 Comput Assist Tomogr 1989; 13: 621-6. 25. Lorigan JG, Libshitz HI. MR imaging of malig­nant pleural mesothelioma. J Comput Assist To­mogr 1989; 13: 617-20. 26. Heelan RT, Martini N, Westcott JW, et al. Car­cinomatous involvement of the hilum and media­stinum: Computed tomographic and magnetic re­sonance evaluation. Radiology 1985; 156: 111-5. 27. Webb WR, Jensen BG, Sollitto R, de Geer G, McCowin M, Gamsu G, Moore E. Bronchogenic carcinoma: staging with MR compared with stag­ing with CT and surgery. Radiology 1985; 156: 117-24. 28. Ovenfors CO, Batra P. Diagnosis of peripheral pulmonary emboli by MR imaging: an experimen­tal study in dogs. Magn Reson lmag 1988; 6: 487-91. 29. Kauczor HU, Layer G, Schad LR, et al. Clinical application of MR angiography in intrathoracic masses . .1 Comput Assist Tomogr 1991; 15: 409-17. 30. Vinitski S, Pearson MG, Karlik SJ, et al. Differen­tiation of paarenchymal lung disorders with in vitro proton nuclear magnetic resonance. Magn Reson Med 1986; 3: 120-5. 31. Mirowitz SA, Gutierrez E, Lee JKT, Brown JJ, Heiken JP. Normal abdominal enhancement pat­terns with dynamic gadolinium-enhanced MR imaging. Radiology 1991; 180: 637-40. 32. Zeman RK, Dritschilo A, Silverman PM, et al. Dynamic CT vs 0.5T MR imaging in the detection of surgically praven hepatic metastases . .1 Comput Assist Tomogr 1989; 13: 637-44. 33. Mathieu D, Rahmouni A, Anglade MC, et al. Focal nodular hyperplasia of the !iver: assesment with contrast-enhanced Turbo FLASH MR imag­ing. Radiology 1991; 180: 25-30. 34. Pavone P, Giuliani S, Cardane G, et al. lntraar­terial portography with gadopentetate dimeglumi­ne: improved liver-tolesion contrast in MR imag­ing. Radiology 1991; 179: 693-7. 35. Mirowitz SA, Brown JJ, Lee JKT, Heiken JP. Dynamic gadolinium-enhanced MR imaging of the spleen: normal enhancement patterns and evaluation of splenic lesions. Radiology 1991; 179: 681-6. 36. Ohtomo K, Fukuda H, Mori K, Minabi M, ltai Y, lnoue Y. CT and MR Appearances of splenic hamartoma. J Comput Assist Tomogr 1992; 16: 425-8. 37. Fernandez MP, Bernardino ME, Neylan JF, Olson RA. Diagnosis of pancreatic transplant dysfunc­tion: value of gadopentetate dimeglumine-enhanc­ed MR imaging. AJR 1991; 156: 1171-6. 38. Krestin GP, Friedmann G, Fischbach R, Neufang KFR, Allolio B. Evaluation of adrenal masses in oncologic patients: dynamic contrast-enhanced MR vs CT. .1 Comput Assist Tomogr 1991; 15: 104-10. 39. Rofsky NM, Weinreb JC, Bosniak MA, Libes RB, Birnbaum BA. Rena! lesions characterization with gadolinium-enhanced MR imaging: efficacy and safety in patients with renal insufficiency. Radiology 1991; 180: 85-9. 40. Neuerburg JM, Bohndorf K, Sohn M, Teufl F, Guenther RW, Daus Hj. Urinary bladder neo­plasms: evaluation with contrast-enhanced MR imaging. Radiology 1989; 172: 739-43. 41. Shonnard KM, Jelinek JS, Benedikt RA, Krans­dorf MJ, CT and MR of neurofibromatosis of the bladder. J Comput Assist Tomogr 1992, 16: 433-8. 42. Neuerburg JM, Bohndorf K, Sohn M, et al. Staging of urinary bladder neoplasms with MR imaging: Is Gd-DTP A helpful? J Comput Assist Tomogr 1991; 15: 780-6. 43. Beltran J, Chandnani V. McGhee RA? Kursuno­glu-Brahme S. Gadopentetate dimegumine-en­hanced MR imaging of the musculoskeletal sy­stem. AJR 1991; 156: 457-66. 44. Seeger LL, Widoff BE, Bassett LW, Rosen G, Eckardt JJ. Preoperative evaluation of osteosarco­ma: value of gadopentetate dimeglumine-enhanc­ed MR imaging. AJR 1991; 157: 347-51. Radio/ Oncol 1992; 26: 140-4. The response of two vincristine resistant human larynx carcinoma celi clones to chemotherapeutic drugs Maja Osmak1 and Damir Eljuga2 1 Ruder Boškovic Institute, Department of Experimental Biology and Medicine, Zagreb, Republic of Croatia 2 Central Institute for Tumors and Allied Diseases, Department of Gynaecology, Zagreb, Republic of Croatia We selected two vincristine (VCR) resistant elones: VAJ and VK2 obtained from human larynx carcinoma cel/s through two different resistance development shedule (acute or continuous), and determined their sensitivity to severa! cytostatic drugs widely used in cancer treatment. Both elones were reisistant to VCR, but VAJ was more resistant than VK2 elane. The resistance to VCR was partially reversed by addition of verapamil indicating that some additional mechanism, beside the increased activity of P-glycoprotein, has to be involved in resistance to VCR. Selected elones change their sensitivity to examined drugs. They became resistant to Adriamycin (VK2 elane), 5-fluorouracil (VK2 elane) and methotrexate (both elones). They did not change their sensitivity to vinblastine, etoposide (Et) or mitomycin C (MMC), except for low concentrations of Et (resistance of VK2 elane) and MMC (sensitivity of VAJ elane). Both elones became sensitive to cis-diamminedichloro­platinum (II), especially VK2 elane. Our results show that drug sensitivity of resistant elones depends on the VCR resistance development schedule. They empasize the complexity and difficulties of judicious choice of agents given in combined tumor therapy. Key words: vincristine; drug resistance; celi cultures; drug therapy Introduction The major problem in cancer chemotherapy is the ability of tumor cells to develop resistance to chemotherapeutic drugs. While some mecha­nisms of resistance allow cells to survive expo­sure to a single agent, the phenomonom of multidrug resistance (MDR) confers upon cells Corespondence to: dr. Osmak M the ability to withstand exposures to many structurally unrelated antineoplastic drugs. The MDR phenotype can be obtained when the cells are selected with: Vinca alkaloids, antibo­tics and anthracyclines.1' 2 However, MDR does not result from selection with antimetabolites, most alkylating agents or bleomycin. The MDR process has been extensively stu­died in animal and human celi lines.3-9 MDR cells are characterized by reduction in intracel­lular drug accumulation, that correlates with UDC: 616.22-006.6-085-092.4:615.277.3 overexpression of a highly conserved 170 kDa Multidrug resistance plasma membrane glycoprotein, termed P-gly­coprotein, an energy dependent efflux pump. The mdrl gene coding for this glycoprotein has been isolated and sequenced. This gene is usually amplified and overexpressed in many MDR cells lines, although in some cases the overexpression of mdr gene with no DNA am­plification was observed. In spite of the fact that mechanims that contribute to MDR phenotype is known today, it is not possible to judge precisely and comple­tely for the cells from each tumor, how the chemotherapy will influence the resistance de­velopment to drugs used, as well as their cross­resistance to other therapeutic agents. The drug resistant sublines of human cells developed in vitro may contribute to the knowledge concern­ing this subject. In my previous study I reffered the resistance development of human larynx carcinoma HEp2 cells to vincritine sulfate (VCR) by two schedu­les: ie. by acute or chronic repeated treat­ments.10 VCR resistant cells were doned, and two dones were selected. VA3 done was obtained from acute treated cells and VK2 from chronic treated cells. The aim of this study was to determine the sensitivity of these dones to severa! widely used chemotherapeutic drugs, that kili cells through different mechanisms: vincristine, vinblastine (VBL), Adriamycin (Adr), mitomycin C (MMC), etoposide (Et), 5-fluorouracil (5-FU), methotrexate (MTX), and cis -dichlorodiammineplatinum(II) (cis­DDP). Materials and methods Cell line Human larynx carcinoma HEp2 cells were used in this study. They were grown as a monolayer culture in Eagle's minimum essential medium (GIBCO) supplemented with 10 % fetal bovine serum (GIBCO) and antibiotics in a humid atmosphere containing 5 % CO2 . Drugs Vincristine sulfate (Oncovin; Eli & Lilly, India­napolis, USA), vinblastine (Velbe, Eli&Lilly, Indianapolis, USA), verapamil (Isoptin; Lek, Ljubljana, Slovenia), 5-fluorouracil (SBS, Bo­snalijek, Sarajevo, Bosnia and Herzegovina) and etoposide (Etopol, Krka, Novo mesto, Slovenia) were dissolved in physiological saline. Cis-dichlorodiammineplatinum(II) (Johnson­Mathey Research Center, U. K.), methotrexate (Roger Belon Laboratories, France), mitomi­cyn C (Sigma Chemical Co., St. Louis, USA) and Adriamycin (Farmitalia Carlo Erba, Italy) were dissolved in water. Stock solutions were stored at -200 C ( except 5-FU stored at room temperature and etoposide at 4° C) and kept in the dark. Drugs were diluted with medium to appropriate concentration just before use. MTT (3-( 4,5-dimenthylthiazol-2-yl)-2,5-dip­henyltetrazolium bromide) (Sigma Chemical Co.) was dissolved in phosphate buffered saline and stored at 4° C protected from light. Resistance development The development of resistance was described in details previously. JO Briefly, the cells resistant to vincristine sulfate (VCR) were obtained due to two drug treatment schedule: they were treated for 1 h in serum-free medium with step­wise increased concentrations of VCR (from 1 to 8 µM) for V A15 cells, or incubated for 24 h in medium supplemented with serum with in­creased concentrations of VCR (from 0.05 to 0.4 µM) for VK15 cells. VCR resistant cells were doned and two dones were selected for futher investigation: V A3 done from V A15 cells, and VK2 done from VK15 cells. MTT microculture assay Chemosensitivity of VCR resistant dones and control cells to different chemotherapeutic drugs was determined using a modified MTT dye assay . 11 This is a colorimetric assay based on the ability of viable cells to reduce a soluble yellow tetrazolium salt to purple colored forma­zon cristals due to mitochondrial enzyme succi­nate dehydrogenase. The cristals can be dissol­ved and quantified by measuring the absorbance of the resultant solutions indicating the number of live cells.12 Osmak M and Eljuga D The cells were plated into tissue culture 96­well microtiter plates at 5 x 103 celi in 0.08 ml medium/well. Next day appropriate concentra­tions of different drugs were added in 0.02 ml/ well ( each concentration was tested in quadripli­cate), and were present contineously for 48 h at 37 ° C. After this incubation period the me­di um was aspirated, 20 µg of MTT dye/0.04 ml medium added to each well and incubated for 4 h. Dimethyl sulfoxid was added to each well (0.170 ml), plates were mechanically agitated for 5 min and optical density at 540 nm determi­ned on a microculture plate reader. Each expe­riment was repeated at least twice. Statistics Significance of the differences in sens1t1V1ty between control cells and resistant dones was assessed by Student's t-test. The leve! of signi­ficance was set at 0.05. Results and discussion In the present study we examined the sensitivity of two vincristine resistant dones of human larynx carcinoma HEp 2 cells, obtained by two different resistance development procedures, to severa! chemotherapeutic drugs widely used in cancer patients treatment. We found that VINCRISTINE . 100 (f) 80 o CONTROL ..J ..J o V K 2 60 w ¦ VA 3 u 40 20 ..J CD o _µg /ml Figure l. Dose response curves of human larynx carcinoma HEp2 control cells and vincristine resistant clones VK2 and V A3 treated with vincristine sulfate. The data are presented as the percent of corresponding control optical density. Pooled data from three expe­riments (mean at each point ± S D). both, VA3 and VK2 dones exhibit, as expec­ted, resistance to VCR. However, cells treated by acute schedule with VCR -V A3 done, were more resistant to this drug than VK2 done obtained by continuous treatment (Figure 1). Therefore, the degree of resistance to VCR was influenced by procedure of resistance develop­ment. The mechanisms involved in resistance to VCR was explained due to addition of verapa­mil. Verapamil binds directly to plasma mem­brane P-glycoprotein. 13 Presumably by blocking cytotoxic drug binding and efflux through com­petitive inibition mechanism, it reverses the MDR resistance.14 In our study addition of verapamil reversed the VCR resistance of V A3 and VK2 dones, but only partially (Figure 2). These data indicate that some additional mecha­nisms, beside the increased activity of P-glyco­protein, have to be involved in this phenome­ nom. The cross-resistance of V A3 and VK2 dones to drugs which can induce MDR phenotype, ie. Adriamycin, vinblastine and mitomycin C, are presented in Figure 3. Both VCR resistant dones were cross-resistant to Adriamycin (with more resistant VK2 done), as published pre- VINCRISTINE C ONT ROL 100 100 .----------. "' .. 60 40 40 ­ 20 20 (J) o+-.-.-..-.--1 o ...J o 0.002 ao2 0.2 2 20 O 0.002 0.02 0.2 2 20 ...J µg/ml µg/ml UJ VK2 U 100-­ UJ O CONTROL ...J • CONTROL , Ver (D 60 C VAJ ¦ VAJ •Vtr - 40 4 VK 2 20 • VK 2 • Ver •+-...--...-.... O 0002 0.02 0.2 2 20 µg/ml Figure 2. Dose response curves of control HEp2 cells and YCR resistant clones VK2 and V A3 following treatment with vincristine sulfate alone or in combina­tion with verapamil. Pooled data from three experi­ments (mean at each point ± S D). Multidrug resistance viously in the literature.9• 15-18 They did not, 5-FLUOROURACIL METHOTREXATE however change their sensitivity to VBL or MMC (V A3 done exhibits even increased sen­sitivity to low concentrations of this drug). It must be pointed out, that establishment of resistance and cross-resistance are distinct phe­ 10 100 ,ooo 10.000 O 0.01 0.1 1 10 100 u nomena. In fact, in multidrug resistant cells, )Jg/ml )Jg/ml the resistance is almost always greatest to the drug used for initial challenge. In our study we used low concentrations of VCR for resistance development, similar to those, which are used in dinical treatment. Therefore, the resistance to challenging agent was much lower than pu­blished in the literature, 15-17 probably too low to induce cross-resistance to VBL or MMC. Similarly, the cross-resistance to etoposide was found only for low concetrations of this drug in VK2 done. It should be mentioned, how­ever, that MDR phenotype of etoposide resi­stant cells involve altered activity of DNA-to­poisomerase II enzymes, not increased activity 46 of P-glycoportein. 3•• The sensitivity of V A3 and VK2 done to: 5-fluorouracil, methotrexate and cis-dichloro­diammineplatinum (II), which do not induce MDR phenotype, were also examined, and the ADRIAMYCIN VINBLASTINE ,OQ ,oo 80 80 o' 60 60 40 40 (/) 20 20 ...J ...J o ,1 ' ' w 002 0.2 2 20 200 µg/ml u MITOMYC w,oo ,oo 00 '° (l) 40 20 20 O 0.02 0.2 2 20 200 )JQ / ml Figure 3. Dose response curves of control HEp2 cells and VCR resistant clones VK2 and V A3 following treatment with Adriamycin, vinblastin, etoposide and mitomycin C. Pooled data from at least two experi­ments (mean at each point ± S D). w "° CISPLATIN ...J O CONTROL 00 []J O VK2 40 o n2 2.0 20 200 2.000 µg /ml Figure 4. Dose response curves of control HEp2 cells and VCR resistant clones VK2 and V A3 following treatment with 5-fluorouracil, methotrexate, and cis­dichlorodiammineplatinum(TI). Pooled data from at least two experiments (mean at each point ± S D). results are presented in Figure 4. VK2 done exhibited cross-resistance to 5-FU, and both dones became cross-resistant to MTX, althoug the mechanisms involved in resistance to these drugs do not involve increased activity of P-gly­coprotein. 4·6·7 Both dones exhibited collateral sensitivity to cis-DDP, especially VK2 done. We can condude that there is a great variety in cross-resistance pattern of human MDR li­nes. The basis for this diversity is not yet fully understood. It appears that factors such as tumor celi type, primary selection agent and resistance development schedule, method of assessment of cytotoxicity and variability in P-glycoprotein (in a paper published recently the diversity of cross-resistance profiles was found to depend on alternative splicing of mdrl gene product in different VCR resistant dones -19) may all contribute to this subject. The finding that VCR resistant cells may ( depending on resistance development schedule) exhibit cross-resistance to different anticancer drugs, which are not able to induce over-expression of P-glycoprotein, emphasize the complexity, difficulty and importance of judicious choice of agents that would be used in the combined therapy of tumors. Osmak M and Eljuga D Acknowledgement We thank Mrs. Lj. Krajcar for her excellent technical assistance. This project was supported by the Ministry of Science and Technology of the Republic of Croatia and by Croatian League against Cancer. References l. Biedler JL, Chang TD, Meyers MB, Peterson RHF, Spengler BA. Drug resistance in Chinese hamster lung and mouse tumor cells. Cancer Treat Rep 1983; 67: 859-67. 2. Riordan .IR, Deuchars K, Kartner N, Alan N, Trent JM, Ling V. Amplification of P glycoprotein genes in multidrug-resistant mammalian cel! lines. Nature (London) 1985; 316: 817-9. 3. Moscow JA, Cowan KH. Review. Multidrug resi­stance . .l Natl Cancer lnst 1988; 80: 14-20. 4. Osmak M. Molecular mechanisms of chemothera­peutic drug-resistance. A review. Radio! !ugasi 1990; 24: 65-70. 5. Kaye SB. Multidrug resistance. Oncology Today 1990; 2: 4-7. 6. Borst B. Genetic mechanisms of drug resistance. A review. Acta Oncol. 1991; 30: 87-105. 7. Dietel M. What's new in cytostatic drug resistance and pathology. Path Res Practl 99l; 187: 892-905. 8. Beck WT, Danks MK. Characteristics of multi­drug resistance in human tumor cells. In: l. B. Roninson, ed., Molecular and Cellular Biology of Multidrug Resistance in Tumor Cells, 1991, Ple­num Publishing Corporation, 3-55. 9. Melera PW, Biedler JL. Molecular and cytogene­tic analysis of multidrug resistance associated gene amplification in Chinese hamster, mouse sarcoma, and human neuroblastoma cells. In: l. B. Ronin­son, ed., Molecular and Cellular Biology of Mul­ tidrug Resistance in Tumor Cells, 1991, Plenum Publishing Corporation, 117-45. 10. Osmak M. Collateral resistance or sensitivity of human larynx carcinoma HEp2 cells resistant to cis-dichlorodiammineplatinum(II) or vincristine sulfate. Neoplasma 1992; 39: 197-202. 11. Mickisch G, Fajta S, Keilhauer G, Schlick E, Tschada R, Alken P. Chemosensitivity testing of primary human renal celi carcinoma by tetrazo­lium based microculture assay (MTT). Uro! Res 1990; 18: 131-6. 12. Mosmann T. Rapid colorimetric assay for cellural growth and survival: application to proliferation and cytotoxicity assays . .l lmmunol Methods 1983; 65: 55-65. 13. Safa AR, Glover CJ, Sewell JL, Meyers MB, Biedler JL, Felsted RL. Identification of the mul­tidrug-resistance related membrane glycoprotein as an acceptor for calcium channel blockers . .l Biol Chem. 1987; 262: 2166-70. 14. Tsuruo T, lida H, Tsukagoshi S, Sakurai Y. Overcoming vincristine resistance in P388 leuke­mia in vivo and in vitro through enhanced cytoto­xicity of vincristine and vinblastine by verapamil. Cancer Res 1981; 41: 1967-72. 15. Tsuruo T, lida H, Ohkochi E, Tsukagoshi S, Sakurai Y. Establishment and properties of vincri­stine-resistant humsan myelogenous leukemia K562 . .lpn .l Cancer (Gann) 1983; 74: 751-8. 16. Conter V, Beck WT Acquisition of multiple drug resistance by CCRF-CEM cells selected for diffe­rent degrees of resistance to vincristine. Cancer Treat Rep 1984; 68: 831-9. 17. Lemontt JF, Azzaria M, Gros P. Increased mdr gene expression and dereased drug accumulation in multidrug resistant human melanoma cells. Can­cer Res 1988; 48: 6348-53. 18. Bradly G, Naik M, Ling V. P-glycoprotein expres­sion in multidrug-resistant human ovarian carci­noma celi lines. Cancer Res 1989; 49: 2790-6. 19. Devine SE, Hussain A, Davide JP, Melera PW. Full lenhgt and alternatively spliced pgp 1 tran­script in multidrug-resistant Chinese hamster lung cells . .T Biol Chem 1991; 266: 4545-55. Radio/ Oncol 1992; 26: 145-9. Stability of complex compounds distinguished by different levels in tumorous vs. identical healthy tissues Damir Huljev,1 M. Džajo2 , K. Košufo?, Z. Rajkovic-Huljev3 1 Središnji institut za tumore i slicne bolesti, Laboratorij za eksperimentalnu kancerologiju, Zagreb Institut »Ructer Boškovic«, Laboratorij za nuklearnu kemiju i radioekologiju, Zagreb 3 Bolnica za tuberkulozu pluca, Zagreb, Croatia Formation constants of metals (11) complexes with severa! amina acids, sugars and acids have been investigated by applying Schubert's method and using 65Zn, 57Co, 89 • 90Sr and 55• 59Fe as the radioactive tracers. Experiments were performed at pH 7.8 which was adjusted by the additio of barbital bujfered solution. Experiments were carried out at constant ionic strenght (1 = 0.16), T = 298 K and ali systems were 0.125 M NaCl. Ali the complex ions formecl were of the 1:1 type. Formation constants (log Kf in brackets) were determined for: Zn-glycine (3.0), Zn-serine (3.3), Zn-aspartic acid (3.4), Zn-methionine (2.2), Zn-cysteine (3.3); Co-glycine (2.5), Co-serine (2.2), Co-aspartic acid (3.6), Co-acetic acid (0.9); Sr-glutamic acid (O. 7), Sr-acetic acid ( 0.04), Sr-ascorbic acid (0.4), Sr-diethyl barbituric acid (0.5); Fe-glycine (3.8), Fe-glucose-1-phosphate (4.0), Fe-amino glucose (3.5), Fe-ascorbic acid (2.5), and Fe-acetic acid (2.2). Key words: organometallic compounds neoplasms-analysis; radioactive tracers Introduction The capacity of amina acids, sugars and organic acids to form metal complexes is of theoretical and practical significance in understanding the biological action of these metal ions. Though there is considerable information about forma­tion constants of metal complexes of amina acids1 • 2 and sugars.3 The physical chemistry of amina acid, sugar and organic acid compounds containing zine, cobalt, strontium and iron has Correspondence to: Dr. Damir Huljev, Central Insti­tute for Tumors and Allied Diseases, Ilica 197, 41000 Zagreb, Croatia not been thoroughly investigated. Therefore, data on the formation of such componds, their stability and structure are of general interest. Previously it has been shown how ion ex­change reactions, in combination with radiotra­cers, can be used for measuring the dissociation constants of complex ions.4• 5 Quantitative measurements of the stability of the complex ions formed between trace metals and the compounds involved in the tricarboxylic acid cycle are of fundamental importance for the elucidation of many biochemical problems.4 Complex organometal compounds are molecu­les containing an organic and an inorganic com­ponent bound to a metal as the central atom. UDC: 616-006.6-074:547.447 The organic part can be an amina acid, sugar, Huljev D et al. methyl group etc., the inorganic component is accounted for by chlorine, bromine, iodine and other atoms or ions, whereas the usual metal atoms are Fe, Co, Zn, Cu, Mg, Se, Pt, Pd, etc. A chelate is a metal complex in which one or more ligands (attached groups) are bound to the metal atom via 2 or more donor atoms. A carrier-free radioactive element is one which does not have weighable or visible amounts of inactive isotopes of that element associated with it. It is believed that many complex compounds and chelates may cause a malignant process in experimental animals. These compounds can also have an antitumorigenic activity. 6 The cytostatic activity of complex compounds depends on the type of organic and inorganic ligands bound to the central metal atom, on the metal present in the complex as well as on the type of the treated tumor. This investigation was concerned with the determination of the chemical stability of com­plex compounds -organic molecules bound to essential metal -present in the human body. Their leve! increases or decreases as the tumor disease progresses. It is stili not clear if the development of such complex compounds is due to the tumorigenic process or, conversely, if the latter is due to the development of such complex compounds in the body. Tests have shown considerable differences between stabi­lity constants of complex compounds of the same metals with different ligands, and of the same ligands with different metals, the influence of the organic ligand functional groups being nevertheless dominant. 7 Materials and methods The synthetic organic cation exchanger, Dowex­50, was used particularly because its capacity is independent of pH over a wide pH range. The universal veronal buffer devised by Michaelis was employed. All reagents were analytical grade. Twelve reaction flasks were prepared according to the data listed in Table l. Flask 1 contained no ion exchanger, NaCl or ligand and was used to determine radionuclide adsor­ption on glass. Flask 2 contained no exchanger or ligand, and was used to determine radionu­clide adsorption on glass in the presence of Na + ions. Flask 3 contained no Na + ions or ligands, and served to determine the maximum percentage of radionuclide binding to the ion exchanger without the influence of Na + ions and the ligand. Flask 4 was used to determine the magnitude of radionuclide adsorption on the exchanger under the influence of Na + ions, and it therefore contained no ligand. The remai­ning flasks contained all the components, the ligand concentration having been progressively higher from flask 5 through 12. The data obtai­ned in this way can be used to calculate the percentage of radionuclide binding to the ion exchanger (Dowex 50, Na + form) as influenced by increasing ligand concentrations. Such data and the listed forrnulae can be used for calcula­ting the stability constants of the used and obtained complex compounds. As indicated in Table 1, specific quantities of different substan­ces were added to each of the 12 Erlenmayer flasks with ground stoppers. The flasks were sealed with paraffin coated stoppers and mixed intensely for 1 hour on an electric shaker. When equilibrium was reached, 1 ml of solution was withdrawn from each flask and the radioac­tivity measured on a single-channel scintillation counter. This procedure provided data on radionuclide quantity in the reaction solution. By deducing this activity from the totally added activity (flask 2), radioactivity bound to the ion exchanger was obtained. A detailed explanation with diagrams and mathematical operations has already been presented.3•8 By introducing the value for the radioactivity of the solution and of the ion exchanger into equation (a), the constant stability of the developed complex compounds can be calculated. The results obta­ined are reviewed in Table 2. Results Formation constants (1/stability constants) Kr were calculated from the equation: Stability constants of meta/s complexes Kr = (Kd0/Kd)-1/(A)" (a) where Kd0 and Kd are distribution coefficients obtained in the absence and presence, respecti­vely, of the ligand A, and n is the number of moles of A relative to the metal ion M. The distribution coefficient for the cation M is defi­ned as: Kd = (% M in exchanger) X (volume of solu­tion-ml)/(% M in solution) x (mass of exchan­ger-mg) the term Kd0 can be obtained directly or from Kd by graphical or analytical means. It is con­venient to plot 1/Kd versus (A)" and to extra­polate the straight line for proper n values to zero concentration of A, as indicated by the relation: 1/Kd = l/Kd0 + (N) x Kf/ Kd0 Equation(a) can be rewritten: log(Kd0/Kd-1) = n log(A) + log Kf Table l. Components of Erlenmayer flasks in the determination of stability complex compouncls Flask Dowex-50 (Na + -form) Raclionuclicle (carrier-free) 0.125 MNaCI ml Ligands ml Distillecl water ml mg ml 1 / 10 / / 90 2 / 10 80 / 10 3 100 10 / / 90 4 100 10 80 / 10 5 100 10 89 1 o 6 100 10 88 2 o 7 100 10 87 3 o 8 100 10 85 5 o 9 100 10 82 8 o 10 100 10 78 12 o 11 100 10 65 25 o 12 100 10 50 40 o Table 2. Formation (1/stability) constants of complex Zn, Co, Sr ancl Fe compouncls Organic compouncls Metals Formation (1/stability) Metal : ligancl (ligancls), L M constants, Kf log Kf M:L glycine (gly) Zn 3.0 1: 1 serine (ser) Zn 3.3 1:1 aspartic acicl ( asp) Zn 3.4 1:1 methionine (met) Zn 2.2 1: 1 cysteine ( cySH) Zn 3.3 1:1 acetic acid (aca) Co 0.9 1: 1 gly Co 2.5 1:1 asp Co 3.6 1:1 ser Co 2.2 1:1 . glutamin acid (glu) Sr 0.7 1:1 aca Sr 0.04 l.: 1 ascorbic acicl (asa) Sr 0.4 1:1 diethylbarbituric acicl Sr O.S 1:1 gly Fe 3.8 1:1 glucose-1-phosphate Fe 4.0 1:1 amino glucose Fe 3.5 1:1 asa Fe 2.5 1:1 aca Fe 2.2 1:1 H uljev D et al. A plot of log (Kd0/Kd-l) versus log (A) should be straight with slope n. The value of log Kf is the intercept of the straight line. Plots of 1/Kd vs. (A) were linear, indicating that ali the complexes were of the 1: 1 type, i. e. n = l. The results are summarized in Table 2. Discussion The Schubert method can also be used to determine the stability of inorganic complex compounds which also play an important role in celi and tissue composition. Ali the tests are run at constant temperature, ion strength and pH values, because these fac­tors influence the stability constants of complex ions.5 As shown by Table 2, the Zn and Fe complexes are the most stable, followed by Co; the Sr complex is the least stable, which con­forms to the data reported in the listed referen­ces. The results of our experirnents show the stability constants of the tested compounds to be fairly high, meaning that these molecules are pennanent components of the cells and tissues of living beings and humans. The determination of the stability constant of complex organic and inorganic compounds is of a manyfold importance. It is well known that compounds displaying a higher stability constant in the physiological medium are gene­rally more stable and have a longer biological half-life. Such determinations have become even more important after the discovery that many complex compounds may cause certain disturbances, malignant processes included, in the body. Some complex compounds have also been found to possess an antitumorigenic acti­vity. 6 Ali this has very much enhanced the interest in synthesis of many complex com­pounds and in the measurement of their stabi­lity in physiological circumstances. Conclusions The following conditions must be fulfilled for the method described: a. l. Formation of anionic or neutral comple­xes which do not exchange on the cation exchanger. 2. Use of a very low concentration of metal ions (Amersham) less than 10-8M. 3. Use of an excess concentration of the ligands (amino acids, sugars and acids). 4. Measurements made at high and constant ion strength. 5. No significant interaction between metals (Zn, Co, Sr and Fe) and the buffer compo­nents. 6. Most of the metal ions were bound to the resin. 7. Adsorption of a complex ion on the ion exchanger was not significant. b. Radioactivity was measured by a 3 x 3 inch Nal (TI) well type crystal, scintillation coun­ter attached to an automatic present tirne counter (LKB compugama, gamma-tipe no. 1282-002). c. Due to the high and constant ionic strength, it is possible that Zn, Co, Sr and Fe have to compete with the excess of sodium ions in complex formation. For this reason the results for the stability constants are signifi­cantly lower than in literature. d. Relative errors: range (2-10 % ). References l. Sillen LG, Martell AE. Stability constants of metal ion complexes. The Chemical Society, Special publi­cation, No. 17, 1964. 2. Sillen LG, Martell AE. Stability constants of metal ion complexes. The Chemical Society, Special publi­cation, No. 25, 1971. 3. Huljev D, Džajo M, Kristic N, Strohal P. The interaction of mercury(II) ions with sugars and amino acids. Jntern J Environ Ana! Chem 1983; 15: 53-9. 4. Schubert J, Lindenbaum A. Complexes of calcium with citric acid and tricarballylic acids measured by ion exchange. Nature 1950; 166: 913-4. Stability constants of meta/s complexes 5. Schubert J. Complexes of alkaline earth cations 7. Pauling L. Metal-metal bond lengths in complexes including radium with amino acids and related of transition metals. Proc Nat Acad Sci USA 1976; compounds. J Amer Chem Soc 1954; 76: 3442-4. 73: 4390-3. 6. Das M, Livingstone SE. Cytotoxic action of some 8. Huljev D, Spaventi Š, Strohal P, Maricic Ž. Izracu­transition metal chelates of Schiff bases derived navanje konstanti stabilnosti helata metodom radio­from s-methyl-dithiocarbazate. Br J Cancer 1978; trasera. Radio! lugosl 1971; 5: 201--6. 37: 466-9. Radio/ Onco/ 1992; 26: 150-6. Personnel exposure to radiation at biliary interventional radiological procedures with an overhead tube Andras K6nya and Z. Vigvary Department of Radiology, Semmelweis University of Medicine, Budapest, Hungary Personnel exposure to radiation was investigated during percutaneous biliary interventions (PTBD ). In this study TLDs were used for each of the following sites: radiologist's eyes, thyroid, hands and assisting nurse's hand and thyroid without shielding apron, as well as radiologist's gonads under the apron. Dose during 6 PTBD sessions (68 min.) was measured by TLDs; from these data the dose!min values relevant to the given regions were calculated. In the course of 9 months during 69 interventions performed by the same staff, the fluoroscopy tirne necessary for the manipulation was measured, so the dose x tirne products relevant to the different regions could be determined. The radiologist's dose!min values were 0.17, 0.28, 0.092, 0.057 mGys/min to the right hand, left hand, thyroid and forehead, respectively, during PTBD sessions. The relative values expressing the relationship between the absorbed doses of the unprotected regions and the gonad dose measured under the shielding apron were the following: 172, 281, 91, 56 to the radiologist's right hand, left hand, thyroid and forehead, respectively. The overhead position of the X-ray tube is radiohygienically rather unfavourable and therefore it should not be used as a regular tool in interventional radiology. Key words: biliary tract diseases, interventional radiology; radiation dosage Introduction At the majority of interventional radiological procedures the lengthy fluoroscopy necessary for the required manipulations exposes the per­sonnel to considerable radiation. The more important portion of the radiation exposure is not the whole body dose measured under the protective apron but irradiation of the unprotec­ted parts of the body (arms, hands, head and Correspondence to: Andras K6nya, MD, PhD, Department of Radiology, Semmelweis University of Medicine, H-1082 Olloi ut 78/a, Budapest, Hungary. UDC: 616.361-002-073.75 neck). During the last one and a half decade it bas been a matter of debate whether the radiation dose suffered by such personnel could be adequately monitored by a single filmdose­meter, and if one employs a single dosemeter, where should it be worn, dosemeters under or above the apron are more suitable for the evaluation of the received radiation dose with respect to the differences in maximal yearly acceptable doses of different body areas. 1 In the case of interventional radiologists the under the apron received doses are numerically reported above the value of 0.4 mGy, but in such cases in the unprotected regions very sig­nificant doses go unregistered . 1 As for the determination of the maximal yearly permissi­ Personnel exposure 10 radia/ion ble dose the most exposed and most sensittve parts of the body (lens, thyroid, hands) should be taken into consideration, absorbed radiation doses of the different regions of the body should be determined separately, because the radiation field is not uniform, and therefore, exposures incurred by different portions of the body cannot be even approximatively estimated from the whole body absorbed dose measure­ments. 2--4 Our studies were designed to estimate the exposure incurred by certain, significantly expo­sed body portions of the radiologist and the assisting nurse during percutaneous biliary in­terventions. For dose determinations we em­ployed thermoluminescent dosemeters (TLD). Radiation burden of the two-men team during 9 months of study period (69 interventions) was determined as the product of fluoroscopy tirne and doses-output, with regard to different parts of the examiners bodies. Materials and methods We monitored absorbed doses of the personnel (above all of the radiologist) during percuta­neous biliary interventions. Detailed data are given in Table 1. The TLD dosemeters were prepared either in the form of a disc or a capsule on a ring, attached to the proximal phalanx of the third finger of the radiologist's right and left hands, his collar, outside the apron, to the centre of his forehead and at the leve! of gonads, under the apron. The assisting nurse was provided with only two TLDs, one on the third finger of her hand proximal to the tube, another on the collar, outside the apron. From these data we calculated the dose/min values relevant to the given regions (Table 2). As all the procedures were performed by the same person (A. K.), who is an interventional radiologist with 12 years' experience, the requi­red tirne was not influenced by interpersonal variations of skill, experience or technique. Interventions were performed with an over­head x-ray tube and undercouch image intensi­fier (Siemens Biangulix 125/12/50 tube, focus diameter 1.3. mm, with 4mm aluminium filtra­tion, Tridoros 5S basic equipment with dose automatics). The measured doses were solely due to fluoroscopy as manual contrast injection was never performed in the course of these interventions. Dosimetry was realized through the thermo­luminescent method (TL). The small LiF tablets could be located on different body areas of the radiologist or the technician without hindering the execution of the interventions. The received doses were determined by a comparative met­hod. Tablets used for the interventions were compared to other ones which received known doses from a reference irradiation source (Co­60), according to the following formula: Table l. Percutaneous biliary interventions Patient Radiation field Body diameter kV mA Focus-film distance Fluoroscopy tirne lntervention (cm) (cm) (cm) (min) l. 2. 10 X 12.5 10 X 12.5 14 21 95 110 4 S.S 90 90 14 17 PTBD interna! drainage transformation of external 2/a. 3. 10 X 12.5 10 X 12 21 22 110 110 s.s 6 90 90 10 3 drainage into interna] drainage endoprosthesis implantation control PTBD 1/a. 10 X 12.5 14 95 4 90 11 control PTBD with adjustment of drain 2/b. 10 X 12.5 21 110 S.S 90 13 control PTBD, external drain removal, its tract embolization Tota!: 6 sessions/3 patients 68 minutes K6nya A and Vigvciry Z DR Di = Ti , where DR : reference dose, Di : unknown dose, TR : emitted light intensity of reference tablets, and Ti: emitted light intensity of tablets Ir­ radiated with unknown dose. Under 200 keV the TL materials' sensitivity increases, so that at lower energy levels the same dose elicits greater signal than above 200 keV. This effect of sensitivity increased in the x-ray zone was taken into account as a 35 % increase of absorbed doses. Results Absorbed doses in different regions of the radiologist are presented in Table 2. For the radiologist, the registered doses were the highest on both hands (19.2 mGy and 11.8 mGy respectively). These high doses can be explained by the very unfavourable radiohygie- Table 2. Dose-values in different regions measured (fluoroscopy tirne: 68') R. band 3rd finger L. band 3rd finger Gonad (under tbe apron) Jugulum Forebead Radiologist measured dose/time dose 11.8 10.4 mGy/b = 0.17 19.2 16.9 mGy/b = 0.28 0.068 60.0 µGy/b = 1.0 nic conditions of the percutaneous biliary inter­ventions: the radiologist has to work in the immediate neighbourhood of the primary x-ray beam. That is why both his left hand, holding the needle, and his right band, manipulating the catheter, are exposed to very high doses of scattered radiation. The overhead position of the x-ray tube is radiohygienically rather unfa­vourable which only multiplies these disadvan­tages. As the assisting nurse is positioned at a certain distance (usually 1-1.5 m) from the x-ray tube, she can be regarded as being in a homo­geneous radiation field. The doses measured on the band proximal to the tube and on the juguJum were practically identical (0.028 and 0.027 mGy/min). Since the assistant is standing further away frorn the x-ray tube than the radiologist, and as the dose of radiation decreases by the second power to the distance, she receives significantly lower doses. The absorbent capacity of the protective apron, i.e. its actual radioprotective effect can be estimated from the differences in radiation witb TLDs (mGy). Percutaneous biliary interventions Assisting n ur se measured dose/time dose mGy/min mGy/min 1.9 1.7 mGy/b = 0.028 mGy/min µGy/min 6.2 5.5 mGy/b = 0.092 mGy/min 1.8 1.6 mGy/b = 0.027 mGy/min 3.9 3.4 mGy/b = 0.057 mGy/min Table 3. Radiation exposures of different body portions of tbe radiologist expressed in relative values compared to tbe corresponding gonad doses Gonad (under tbe Absolute value R. band L. band Jugulum Forebead apron, 0.5 mm Pb of tbe dose equivalent) output Percutaneous biliary interventions 172 281 91 56 1 1.0 µGy/min Personnel exposun: to radiation exposure between the covered and uncovered areas; the data are detailed in Table 3. Con­sidering these data, one has to take into account that the differences are to be ascribed not only to the apron's radioabsorption, but also to the differences in distances from the x-ray tube. Hand doses increase in proportion with gonad during the biliary interventions. If we take into account that doses registered with a film dosemeter, under the apron, at the heart leve! do not significantly differ from gonad doses, we can conclude that the radiologist receives unregistered irradiation in doses appro­ximately by two orders of magnitude higher (at least 100 limes higher!) than the values inferred from the evaluation of the dosemeter-film. The data on radiation exposures of certain unprotected body areas of the radiologist during biliary interventions are especially important (Table 4). For the evaluation of these data it is worth mentioning that the same radiologist during the preceeding twelve years has perfor­med severa] thousands of selective catheteriza­tions and has a personal series of about two hundred percutaneous biliary interventions. This extensive experience excludes the possible counterargument that the long fluoroscopy-ti­mes could be explained by the lack of appro­priate experience. It can be read from the table that one intervention consisted of four sessions on average, and a single sessions's average duration was 13.3 minutes. Fluoroscopy tiine in one patient ranged between 12 and 156 minutes (average 51 min). It is evident that in technically complicated obstructions and stenoses fluoro­scopy took much longer than the average (e.g. multiple stenoses treated by double drainage or endoprostheses). It can be seen from these data that the radiologist exhausted more than half of his yearly dose equivalent limit of his left band (259.1 6 mGy) and more than one third of the same for his lens (52.11 mGy) (500 mGy and 150mGy, respectively).2•3 These great doses were received during inter­ventions perfonned in only 18 patients! Discussion As most of the procedures of interventional radiology can be performed only under fluoro­scopic guidance this results in a significant in­crease in radiation burden of both the patient, Table 4. Calculated radiation exposures in percutaneous biliary drainages Patient No. Tota! fluoroscopy . . Exposures of the radiologist (mGy) . . Type of 111tervent10n (n = 18) of sessions tune ( mm. ) r. hand l. hand jugulum forehead l. 2 22 internat drainage 3.74 6.16 2.02 1.25 2. 4 endoprosthesis 8.12 2.67 1.65 3. 3 41 interna! drainage 6.97 11.48 3.77 2.34 4. 3 62 double drainage 10.54 17.36 5.70 2 28 external drainage 4.76 7.84 2.58 1.59 6. 15 156 double prosthesis 26.52 43.68 14.35 7.98 7. 1 17 external drainage 2.89 4.76 1.56 0.97 8. 7 150 external drainage 25.50 42.00 13.80 7.25 1 36 external drainage 6.12 10.08 3.32 1.95 10. 7 71 prosthesis + drainage 12.07 19.07 6.53 4.05 11. 3 38 internat drainage 6.46 10.64 3.50 2.07 12. 3 20 interna! drainage 3.40 5.60 1.84 1.14 13. 1 12 extermal drainage 2.04 3.36 1.93 0.68 14. 4 34 double drainage 5.78 9.52 3.13 1.94 15. 5 75 endoprosthesis 12.75 21.00 6.20 4.27 16. 3 41 endoprosthesis 6.97 11.48 3.77 2.34 17. 1 22 external drainage 3.74 6.16 2.02 1.25 18. 4 59 endoprosthesis 10.03 16.52 5.43 3.36 Tota! 18 69 919 min. 158.99 259.16 84.27 52.11 K6nya A and Vigvary Z and the personnel, with ali its inherent risks. One has to take into consideration that body portions not protected by the apron, e.g. hands and arms, and the head and neck region are exposed unprotected to the scattered radiation. Thus 18 % of the red marrow has no protec­tion. 5 It is sure that as the radiation field is not humogenous, and the yearly limit of different regions' is not the same, the single film-doseme­ter worn under the apron is not an adequate tool for the determination of actually received doses. 1•6 Data in Table 5, with the exception of Cruik­shank's results demonstrate radiation doses re­ceived during interventions with undercouch tubes.7 Faulkner experimentally demonstrated, that if the radiologist is to be positioned in the close proximity of the patient, undercouch tubes are much more favourable, as the examiner's absorbed radiation dose is significantly lower than when the same interventions are perfor­med with overhead tubes.8 Scattered radiation measured at the leve! of thorax and waist, in the immediate vicinity of the table can be reduced to at least one fourth and one sixth of the original value, respectively, simply by inverting the position of the x-ray tube and the image intensifier. In certain re­gions (e.g. the forehead and the lens) overhead position of the x-ray tube increases the scattered radiation leve! to 30 times that received with the undercouch position of the same tube.9 These data explain why our irradiation doses so significantly exceed the similar (sometimes even with one or two orders of magnitude!) values published in the literature. An important aggravating factor in the radia­tion burden is the old age of the equipment, as with our present tube adequate fluoroscopic images could be obtained only by an exceptio­nally high milliamperage (4-7mA). The do­seautomat prevented the manual reduction of these high values. Drainage techniques, such as the percuta­neous biliary drainage and the percutaneous nephrostomy ensuring free urine flow are espe­cially unfavourable with regard to radiation protection, and therefore these interventions deserve special attention. During these inter­ventions the radiologist is standing in the imme- Table 5. Radiation doses incurred by different body portions of radiologists performing percutaneous drainages Author Intervention Average Do ses (mGy) Technical fluoroscopy r. hand l. hand neck fore- characteristics tirne (min.) head Cruikshank PTC l. 13.8 5.15 Overhead tube 1980 (0.373/min) field: 100 cm2 2. 14.0 3.96 (0.295/min) Gustafsson PTC 35.0 1.5 4.0 0.11 0.12 Undercouch tube 1981 70-90 kV,< 1.5 mA PTC 13.0 0.55 1.5 0.04 0.04 2.5 mm AI filtration field: 100 cm2 LePage Endoprosthe­ 35.0 25.0 1.7 No data 1984 sis PTBD ex­ 11.68 8.35 0.57 ternal/internal Geterud Nephrostomy 11.6 0.34 0.63 0.13 Undercouch tube 1989 Percutaneous 70-90 kV, 1-3.6 mA stone extraction 3.5 mm Al filtration K6nya PTBD 36.0 6.12 10.08 3.32 1.95 Overhead tube (external) 95-110 kV, 4-6 mA PTBD 12.0 2.04 3.36 1.93 0.68 field: 125 cm2 (external) 4 mm Al filtration Personnel exposure to radiation diate proximity of the patient, and thus also of the radiation source, while in the course of manipulation his hands are quite close to the primary beam of radiation. These interventions are rather time-consuming and require quite complicated manipulation, so the absorbed dose from fluoroscopy is considerably high. Cruikshank reports on doses received during interventions with overhead x-ray tubes.7 As our data were gathered under similar circum­stances, our results are in accordance with the aforementioned data of Cruikshank. It is rather conspicuous that with the more optimal under­couch position of x-ray tubes the doses in the various regions significantly decreased, al­though the fluoroscopy times did not differ significantly. Compared to the data of Gustafsson, our doses measured on the right and left hands were 2.5 and 4 times higher, respectively.9 The same ratio was strikingly higher for the neck and head (forehead) region; 30-48 and 16-17, respectively. These data support Hoffman's above cited data, according to which the over­head positioning of the x-ray tube can multiply the lens-dose even by a factor of 30 .10 LePage reported exceedingly high doses for the right hand.11 Presumably these results are to be ascribed to the fact that the radiologist had to manipulate even in the primary beam as he performed the biliary drainages from an epiga­strial approach. Based on the above published radiation doses and on the literature the following conclusions can be drawn: l. The problem of personal dosimetry of full­time interventional radiologists has not been solved as yet. Film dosemeters worn under the apron do not correctly inform us about the radiologist's and the assisting nurse's real exposure, since at the same tirne the doses received by different regions with va­rious radiosensitivity remain unknown. Buc­hen found the attenuation factor of the pro­tective apron to be 0.04--0.005, or, in other words, areas left unprotected receive 25-200 times higher doses than the areas under the apron. These data are clearly supported by our own observations.1 2. Equipment with overhead x-ray tubes is un­doubtedly obsolete and from the viewpoint of radiation protection does not fulfil even the minimal requirements, so these devices should not be used as regular tool in interven­tional radiology. We strongly disapprove of such practices. Especially strong is our disap­proval in such cases where special techniques are employed, e.g. drainages (PTBD, percu­taneous nephrostomy), as in these situations the radiologist is positioned in the close vicinity of the tube and the primary beam, and has to manipulate in this area. Today the advantages of interventional radio­logy are indisputable, and one can anticipate that progress in this direction will continue. Personnel has to answer the challenges of ever­growing demands, so the health risks of the increased x-ray exposure should be minimized (using pulse generator, image manipulations, individual protective devices). An important prerequisite of this is the use of reliable local, personal dosemeters. References l. BIR. Recommended position for wearing of per­sonal dosemeters. Statement of the British Insti­tute of Radiology Brit J Radiol 1988; 61: 349-50. 2. ICPR. Recommendations of the lnternational Co­mission on Radiological Protection (ICPR Publica­tion 26) Annals of the ICPR 1977; Vol. 1, No. 3. 3. ICPR. Statement and recommendations of the 1980 Brighton Meeting of the ICPR. Annals of the ICPR 1980; Vol. 4, No. 3/4. 4. NCPR. National Council on Radiation Protection and Measurements: basic radiation protection cri­teria. NCPR. 1971; Report No. 39, Washington. 5. Riley RC, Birks JW, Palacios E, Templeton A W. Exposure of radiologists during special procedu­res. Radiology 1972; 104: 679-83. 6. Law J. Doses to head and arms of radiologists during fluoroscopy (Short communication) Brit J Radio/ 1985; 58: 187-8. 7. Cruikshank JG, Fraser GM, Law J. Finger doses received by radiologists during Chiba needle per­cutaneous cholangiography. Brit J Radio/ 1980; 53: 584-5. K6nya A and Vigvdry Z 8. Faulkner K, Moores BM. An assesment of the 10. Hoffman JR, Staiger JW, Wollan RO et al. The radiation dose received by staff using fluoroscopic Minnesota Special procedure room. Radiology equipment. Brit J Radio/ 1982; 55: 272---6. 1971; 98: 551-9. 11. LePage JR. Failures, complications and interven­ 9. Gustaffson M, Lunderquist A. Personnel exposure tionalist radiation exposures in 108 cases of at­to radiation at some angiographic procedures. tempted biliary endoprostheses. Ann Radiol 1984; Radiology 1981; 140: 807-11. 27(4): 366-70. Radio/ Oncol 1992; 26: 157-64. Nuclear medicine in Macedonia -A continous adaptation to the challenge of medica) practice lsak Tadžer Macedonian Academy of Science and Arts The development of nuclear medicine (NM) in Macedonia started in 1955 after the writer of this paper as a fellow of the WHO visited Russel Fraser' Department of endocrinology at the Postgraduate medica! School, Hammersmith Hospital, London. 1-131 thyroid uptake was assessed there in a small closet. This gave the idea to measure uptake in goitrous patients in Macedonia particulary originating in the western parts where the endemic rate of goiter was up to 80 %. Figure 1 shows the first G.M. set (Philips) in use till now. The beginnings of NM as a convergence of many other scientific disciplines with those of medicine, as an interdependence of basic sciences, medicine and technology8 could not be continued on an amateur basis. The Federal authority for Nuclear energy (SKNE) provided the necessary basis for professional application of NM. A special commission at this authority provided educational and financial help. After the constitution of national (republican) laboratories for NM (1959) regular work started. In the first period, problems of NM per se and safety control were a joint establishment. Very soon safety was separated as an independent entity belonging to the authority of Health and Welfare in Macedonia. Key words: nuclear medicine-trends; Macedonia Radiation protection In 1966 the department of radiation protection started with regular monitoring of radioactive emitters in the environment, in atmospheric aerosols, polution of drinking water, rainfall, milk, foodstuffs, periodical measurements of water resources in rivers and lakes. In 1977 and 1986 monitoring of the ecosystem was upgraded using a 8192-channel semiconductor system (PC-AT 1MB, 16-MHz-processor). The detec­tion of H-3 and C-14, cosmogenic and from reactor (nuclear) was included. At the Veterina­rian Institute where measurement facilities were installed about at the same time the research was focused on imported food and ecological problems. NM in Macedonia Correspondence to: Prof. dr. Tadžer lsak, Macedo­nian Academy of Science and Arts, Bul. Krste Misir­ The Central laboratory for NM started regular kov br. 2, pošt. fah 428, 91000 Skopje, Macedonia. thyroid uptake studies and PBI-131/D/L in UDC: 616-073:539.163 1959. 158 Tadžer I fi,,p ., Figure l. G. M. SET "PHILIPS" since 1956. In 1980 a radionuclide laboratory was organi­zed at the Military Hospital in Skopje in the new central building. In 1983 a new laboratory was opened at the General Hospital "Dr. Trifun Panov" in the very south of Macedonia, in Bitolj. The first nuclear medicine course (1984) in the laboratory of Skopje conveyed enthusiasm to many men and convinced them that future Lies in this speciality. The principals of the laboratories in Skopje and Bitolj were among the first participants of those courses. (Figure 2). The laboratory in Skopje was a real central laboratory providing NM diagnostics and treat­ment to the patients of the General Hospital in Skopje (1500 beds), in the out-patients clinics with a turnover (in some days) of 3000 patients coming from ali parts of Macedonia (population about 2.2 mil.) and from the south parts of Serbia including the whole of the province Kosovo. The use of RIA-programs and ELISA-tech­niques spread very fast in many clinics in inde­pendend units. The detection of hepatitis mar­kers in vitro was transferred from our labora­tory to the department of infectious diseases and to the central blood bank. Macedonia had in some years up to 6 %o of cases with A and B hepatitis and an uknown rate of non-A and non-B (HVC) and hepatitis D cases (Sympo­sium on hepatitis, Macedonian Academy of Sciences, 1991). The search for hepatitis in the blood of donors became compulsory for the whole teritory of Macedonia employing in vitro RIA or ELISA tests. Premises and equipment In 1961 the new premises of the laboratory for NM financed by the Ministry of Health and Welfare of Macedonia and SKNE were ready. The funds for equipment (specific and general) were pending so we had to wait for investment. The earthquake in July 1963 which destroyed the city of Skopje damaged considerably the building. In 1965 the renovation was roughly completed. Most of the work was done in a hurry in unsatisfactory conditions due to ex­treme building difficulties experienced by the whole city ( after the devastating earthquake) and other priorities in this renovation. The laboratory was transfered from the basement of the general hospital in to the nearby new laboratory (Figure 3, 4). The equippment re­mained incomplete, the funds were given for the purchase of a cobalt machine and accelera­tor for the Department of Oncology which badly needed this equipment (Figure 5). Gradually the laboratory was equiped with cameras (a. processors). The staff is stil lob­bying for advanced technology competing with our collegues who introduced CT and favoured the echotomographic explosion in allmost every department. Figure 2. First course in Nuclear Medicine in Skopje 1968. Nuclear medicine in Macedonia The first imaging device in late 1959 was a 4 cm G. M. lead cathode tube enclosed in a "pistole like" thick shield with a narrow cylin­drical collimator (Figure 6). The instrument was produced by a commercial G. M. supplier for manual thyroid seans after a reasonable uptake of 1-131 in the gland with the intent to make a plot of determined isoresponse settings of surface. The next scanner in 1960 was designed and constructed by the Institute of Nuclear Sciences "Jožef Štefan" (Ljubljana) (Figure 7) as the first Yugoslav scanner. The Nal crystal of 1" was shielded for the use of higher photon energies (above 0.2MeV). Thicker septa of the focussing collimator gave satisfactory 1-131 thy­roid seans. The first autonomic nodule was detected in Macedonia by this scanner. Autono­mic thyroid nodule(s) belong to one of the typical thyroid deviations in an iodopenic envi­ronment (water supply in Macedonia has a content of 2-4 gama/L).14 Ali parts of this ·,1; ; : :) Figure 4. Specific equipment (old) in the new labora­tory, RING counter: Twelve LEAD CATHODE G. M. tubes (24cm) used for radioactivity measure­ments in feces and urine in 2-3 L beakers. scanner were constructed or assembled on an artisan basis. The chassis of a typewriter was employed to type analogue images. Thyroid seans were clinical useful. Adjustment for line spacing, spectrometer window setting, distance between the collimator and the patient were learned by experience. NM practice The diagnostic procedures at the General Ho­spital during the first decades underwent an Figure 3. The new Isotope laboratory after renovation following the devastating earthquake in 1963 in Skopje. Figure 5. Gamma counter "wll type" EKCO. 160 Tadžer I .. "' ..: Figure Sa. Thyroicl uptake set since 1962 with a home macle collimator consisting of leacl rings. Designecl in „ the institute of Nuclear sciences "Boris KidricYinca, Belgraclc. uninterrupted adaptation to the requirements of specialists and general practitioners. Table 1 shows the present state of some NM methods today. The previous importance of any particu­lar method is arbitrarily considered as maximal ( 4 points). Placentography with In-113 m labe­led RBC had been important (4 points) until the department of obstetrics acquired an ultra­sound instrument. Over 20 years placentography, in particular the radioisotopic exploration of placenta previa, has been totally abandoned (O points). The number of brain scannings (4 points) has been decreased soon after the introduction of CT brain scan. Dynamic studies of the brain are done occasionally (1 point), whereas cysterno­graphy using DTPA-Tc-99m has remained a method of choice in the evaluation and follow up of hydrocephaLic children (4 points). The application of radionuclides in hemato­logy interested many clinical people. Ferrokine­tic studies with Fe-59 were much used for the diagnosis of anemic patients. The myelopoiesis activity assessment using surface counting with one or severa! detectors was quietly replaced by RES skeleta! Tc-99 m colloid studies; peri­pherisation of bone marrow activity is reserved only for myelofibrosis and patients with aplastic syndromes. Blood volume studies with Cr-51 RBC or Tc-99 m-RBC have been done (about 10-15 yearly) exclusively for the diagnosis and follow up tests in patients suffering from polycythae­mia. The interest for volume studies in surgical practice faded substantially although one of the inventors of simultaneous labeling of plasma volume and RBC volume is a member of the staff of NM.6 '"'j Figure Sb. Gamma probe with 2" crystal for surfacc counting in the extremities using Fe-59. The shielcling is enforcecl by aclclitional leacl coating. Nuclear medicine in Macedonia The determination of life span of Cr-51 RBC has been in steady demand. Macedonia is a well known endemic zone of Cooley's anemia.3 The secondary hypersplenic destruction of RBC in homozygote cases with thalassaemia is regularly tested with Cr-51-autologous RBC; enhanced splenic activity leads to splenectomy. When splenic Cr-51 RBC trapping is enhanced in Minkovsky-Chauffard's disease, splenectomy is the method of choice. Orthojod-hippurate-1-131 renography is stili used in daily practice old gamma counter twin­set constructed in our laboratory from commer­cial parts examines the patients in supine posi­tion (Figure 8). OIH-1-131 is in-house prepared autoclaving radioiodine and OIH. This labeling procedure was introduced by copying the metod of Pinhas Czerniak's (Tei Hashomer Hospital, Israel, Tel-Aviv) in 1961. The rate of use is stili " Figure 6. Manual lead cathode (4cm) G. M. tube with lead shielding and cylindrical collimator for thyroid scanning. 1d: . : .. IJ-i : .. u • Figure 7. and 7-a: Rcctilincar scanner, l" crystal, designed and constructcd in the Nuclcar Institute "JO­ŽEF ŠTEFAN", Ljubljana. maximal (4 points; Table 1). Probably cost/be­ nefit is one of the important assets. The urolo­ gists prefer the screening information of sepa­ rate kidney function. Cost/benefit problems The general economic situation of Macedonia imposed from the beginning austere introduc­tion of NM in ali phases of development. This led to "in house preparation" of many radiola­beled radiopharmaceuticals as OIH-1-131, Rose-Bengale-1-131 which was replaced also by interna! preparation of Tc-99 m-sulfur colloid, Pyrrhophosphate-SnC12 , DTPA-SnC12 . Some N. M. labelings had an ephemeral use. The application of home-made labeled fibrinogen (1-131) for the detection of thromboses particu­larly in the lower extremities was introduced 162 Tadžer I Figure 8. »Twin« gamma set for radiorenography in supine position using OIH-1-'13]. with great success,4 but abandoned by surgeons in spite of fact that a portable garnrna-detector was brought to the patient's bedside (Figure 9. PITMAN battery detector). Kladnik (Ljublja­na) succeded to synthesize an irninodiacetic compound which we had used for biligraphic scaning until the Laboratory for Nuclear Phar­maceuticals, Institute "Boris Kidric", Vinca, started commercial production. On the other hand, some elswhere obsolete and abandoned radio nuclide techniques are stili in use because of the demand of the practitioners: detection of "Resturine" employing OIH-131, radioreno­graphy even radionephrography with a fast moving rectilinear scanner. The daily work on thyroid in vitro tests has increased to 80-100 tests. This forced the intro­duction of total thyroxin and trojodthyroninup­take assay in vitro by a dornestic modification of Murphy's technique. 1 Training in NM Training of the staff was not the usual way of specialisation established by tradition and curri­culum in other medica! specialities. The nucleus of the assistance finished first a 4 rnonth English course at the School for Foreign Languages, than began training at the School for application of radionuclides (Institute of Nuclear Sciences "Boris Kidric", Vinca) where a basic course consisting of over 8 weeks of lectures and Figure 9. PITMAN (U. K.) manual battery gamma ratemeter for bedside body suface counting. laboratory work acquainted physicians, biolo­gists, veterinarians, physicists, chernists etc. with application of radioisotopes. For the first and following generations these courses were indispensable and very useful. At the same period parallel and complementary courses or specialisation were of great help: through the IAEA in Moscow ("Botkin" postgraduate me­dica! school, prof. Modestov), British Council courses in Sheffeld and Leeds, Harnmersrnith -London, Radioisotopes laboratory at Bartho­lomew hospital (Dr. K. Britton), Ville-Juif (Tu­biana), Hospital Pitie Paris and Tours (Therese Planiol), National Institute of Health and Wel­fare (MIT, Boston, J. Stanbury), the Laborato­ries of Nuclear Medicine and Biology (Baltimo­re, Dr. H. Wagner, Jr.), Klinikum Berlin Ste­glitz (Dr. Oef), Berlin-Buch (Laboratory of prof. Dr. Deckart) and many short visits in Europe, SSSR, USA, CSR. Of great help was the infonnal and warm reception of the cowor­kers at the laboratory of the Institute of N uclear Sciences, "Boris Kidric" (Vinca), the Laborato­ries for Nucelar Medicine in Belgrade (Prof. Dr. P. Milutinovic), Ljubljana (prof. Dr. B. Varl, prof. dr. M. Erjavec). Zagreb (prof. Dr. I. Šimunovic). The yearly rneetings of the So­ciety of Nuclear Medicine on a rotating basis in ali important laboratories in Yugoslavia, gave additional impetus for presentation of current results and achievements. There discus­sions and informal contacts at ali levels provi­ Nuclear medicine in Macedonia Table 1. Rating of Requests for Radionuclide Proceclures by Medica! Practice in Maceclonia (rating O, 1. 2. 3. 4 points) Diagnostic methocl ancl Average daily Average daily therepeutic application work ( 1960-75) work ( 1990/91) 11-131 thyroicl uptake 24h 1-131 thyroicl uptake 3-6h PBl-I3I/DOSE/L Te-99 mm thyroid scanning Thyroid echotomegraphy Ferrokintic studies Fe-59 CR-5I RBC life span OIH-I-I3I radiorenography radiorenographic stuclies DMSpTc-99 m renal scanning Cardiac tests-Tc-99 m first pass and venticulographic stuclies Tc-99 rn polyphosphate bone and joint scanning 1-131 treatment of Graves· disease 1-131 treatrnent of toxic thyroicl aclenoma Au-I98-colloicl treatrnent of pleural rnesotheliorna Au-colloid treatrnent of peritoneal malignancies Au-I98-colloicl treatment of chronic rheurnatoid arthritis by synoviexeriesis P-32 treatment of polycythernia prirnaria 4 0-1 4 o 4 o 4 2 o 4 4 o 3 2 o 4 o 4 o 4 4 4 2 3 3 4 1 4 o 4 o 3 4 ded the opportunity for getting acquainted with useful as well as futile methods in NM, which was essential in the view of vigurous, incessant changes of technology, electronics, radiophar­maceutics, dynamic and processing procedures and even scopes in NM. Thus, systematic and incessant exchange of knowledge and experience was crucial at the very beginning and later on. Expansion of NM From its start in 1956 until nowadays the activity of the NM laboratory has been centred on the problems of NM routine considering the de­mands of the practice. Thyroid pathology ini­tially representing about 90 % of the whole work, in use now involved 40-50 % , the next by the frequency of demand are bone scinti­graphies and kidney studies (20-30 % ) whereas the rest goes to cardiology, !iver, cysternogra­phy, adrenal glands lymphography etc. (Table 1). On the other hand, part of the work could be classified as work in connection with some of the acute health problems in Macedonia: programmed thyroid studies in our typical iodo­penic region: although since 1956 the federal law makes the iodination of salt compulsory (10 mgr KJ/1 kg NaCl) the water supply in ali sources is under 4 gama/L. The consumption of salt decreased substantially, and some noniodi­nated salt is avaible in the rural regions and in the food industry. The typical expression of the thyroid pathology observed previously in io­dine-deficient (former) West-Germany was con­firmed in this region: autonomic toxic and non­toxis nodules, dysfunction of the thyroid after iodine contamination, familiarly iodopenic goi­ter in children living in isolated highland villages consuming only iodinefree salt,9 palpable thy­roid grade I in over 8 % of population.7 The quest for scanning hydatid cysts in the !iver disappeared because of the efficient erradica­tion of the disease by the veterinary authority and, second, by the very efficient ultrasound visualisation of cysts. 164 Tadžer I Imaging of posthepatitic sequelae and non­aggressive flow studies are currently on the program imposed by the great number of pa­tients with previous history of viral hepatitis. NM at the University in Skopje The staff is engaged in severa] curricula for undergraduate students at the School of Medi­cine, Dentistry and Pharmacology. Short pre­sentations and educational courses for physi­cians undergoing training in different speciali­ties are on the agenda. Education of medica! technicians and biologists competing for Ma­ster's Degree are also included. Close work with different departments of medicine and surgery brought to attention some previously unobserved phenomena which resul­ted in a number original papers: detection of Milroy's disease using labelled colloid, 10 iodine fractions influencing thyroid tests,1 1 "hot nodu­le" turning cold during methimazole treat­ment,12 labelling of platelets using acetyl ace­tone complexion of In-133 m.13 It is hardly possible to illustrate the merits and endeavours of ali collagues who have hel­ped, contributed and worked on the early deve­lopment of NM in Macedonia. Let me conclude by quoting G. C. Heveshy in his5 Faraday Lecture given on March 29 1950, in Edinburgh: "The application of isotopic indicators in biology opened new lines of ap­proach, not only to the solution of known problems, but also by directing our attention to trains of thoughts not considered previou­sly ... " perhaps this kind of thinking gave a particular stimulus for work in NM. References l. Aleksic Ž, Šestakov G. Kompetitivno odredivanje tiroksina RIA-metodom i kornpetitivnom meto­dom, Radio/ lugosl 1978; 12(2) 451-2. 2. Czerniak Pinhas -person. communic. (SHIBA hospital, Tel-Ashorner, Tel-Aviv, Israel/). 3. Efremov G, Huysman TA, Dirnovski et al. Beta thalassaemia in Yugoslavia. Hemoglobin 1990; 4(1) 15-20. 4. Georgievska B. Detekcija na cllabokite venski trombozi so radiofibrinogen. Medicinski fakultet, Univerzitet »Kiril i Metodij«, Skopje (Doktorska disertacija, 1979). 5. Heveshy GC. The Application of Radioactive Indicators in Biochemistry . ./ Chemical Safety 195]; 1918-39. 6. Korubin V, Brozovic B, Lewis GM, Szur l. Simul­taneous reci celi and plasma volume determination by differential absorption methocl . ./ Lab & Ciin Med 1966; 68: 142-5. 7. Korubin-Dolgova V, Vandevska M et al. Rezi­dium endernske strume u Makedoniji. TV. Jugosl. Sirnpoz. o štitastoj žlezdi. Zlatibor, Zbornik ra­dova 1980, 361-4. 8. Meyer W, Wagner Jr. Nuclear rnedicine -How it Began Hospital Practice book. Nuclear Medicine 1973: 1-14, Baltirnore, John Hopkins University. 9. Siinova N i sar. Pojava gušavosti kot dece usled jodnog deficita. JV. sirnpoziurn štitaste žlezde. Zbornik radova, Zlatibor 1980; 343-5. 10. Tadžer IS. A Sirnple Test for Milroy's Disease. Year book of Nuclear Medicine, Chicago, 1973; 159-60. 11. Tadžer IS, Šestakov G et al. Das Verhalten der Nicht als Jodid Vorliegende Radiojodfraktionen bei Isotopendiagnostik der Schilddri.ise. Nuklear Medizin, veri. Schattauer, Stuttgart, 1975; (6): 411-6. 12. Tadžer IS, Sirnova N. "Hot" Nodule (autonornous nonproliferative) Turning Cold during Methirna­zole treatrnent. Proc. XIII Intern. Annual Mee­ting. Soc Nucl Med, Kopenhagen Proceeclings ed. Fade Kopenhagen 1975; 168: 1-4. 13. Tadžer IS. Oznacuvanje trombocita ln-113 rn i TC-99 rn. Radio/ !ugosl 1980; 14: 240-1. 14. Tošev D i sar. Odreduvanje na sodržinata na jod vo pitkite vodi na Makedonija, trudovi 1970-1980 vo Godišen Zbornik na Prirodno-maternatickiot fakultet na Univerzitetot »Kiril in Metodij«. Sko­pje. Radio/ Oncol 1992; 26: 165-6. The beginnings of radiology in Rijeka Ivan Lovasic Clinical Hospital Center Rijeka, Medica/ Faculty of Rijeka, Institute of Radiology, Croatia The encl of the 19th century represents a great progress for the city of Rijeka. The Holy Spirit Hospital achievecl its autonomy ancl hecame a puhlic health facility; sewage system, water mains ancl electrification were accomplishecl, huilcling of schools ancl the theatre startecl, ancl many puhlic lihraries ancl various societies macle their appearance cluring the last two clecacles. The Natura! Sciences Ciuh, the memhers of which were physicians of Rijeka, teachers ancl other eclucatecl classes, as well as industrialists, wholesalers and proprietors, should he specially pointed out. Through the lectures helcl there, the puhlic was informed ahout the most recent scientific ancl technical achievements in the worlcl. At that time, Military Naval Academy had the most selected teaching staff for the sons of archdukes, counts and ministers from Vienna and Budapest, who attended their lessons there. Among the teachers there was a man of high standing, Prof. Dr. Peter Salcher, Austrian hy origin, horn on August 10, 1848 in Kreuzin-Ehen near Peternion, who was the president and vice-president of the Ciuh severa! times. Key words: radiology; Rijeka Not a full month from Roentgen's lecture held at the session of Physico-Medical Society in Wuertzburg on January 23, 1896, precisely on February 20, 1896, Prof. Peter Salcher held a lecture in Rijeka on roentgen ray discovery and the first radiography was made. On February 24, 1896, daily paper La Bilan­cia reported about Dr. Salcher's lecture held at the Club (nowadays Italian Secondary School in Rijeka). In the lecture the observation that the momentous significance of Roentgen's dis- Correspondence to: prof. dr. I. Lovasic, Medica! Faculty in Rijeka, Clinical Hospital Center Rijeka, Tome Strižica 3, 51000 Rijeka, Croatia. UDC: 615.849 covery was not only to make photos without light and lens, but to image body interior by means of x-rays was pointed out. The light was replaced by electricity in this case and the word "electrography" or even better "roentgenography" should be more logi­cally used instead of photography. Afterwards, the lecturer carried out the following two experiments: First, he conducted e!ectric current from a galvanic battery via Rhumkorff's coil to Hit­torf's tube, i.e. Crookes' tube. He placed a cassette with a sensitive photo plate on the table underneath, and asked one of the present ladies for her assistance in the historical "hand experiment". The greenish fluorescent light ap­ 166 Lovasic I peared inside the tube and the "electrography" of the hand started. In the second experiment the electric current was conducted for Crookes' tube from an in­fluencing apparatus. Coins wrapped in paper and a cardboard box were under the tube. By the end of the lecture the photo plate had been developed. One of them revealed osseous strne­ture of the hand skeleton with a ring shade on the finger. The coin shades and an oval plate with the inscription "Roentgen" could be seen on the other one. Dr. Petar Salcher, the vice-president of the Club at that tirne, strove to establish the Com­mittee for x-ray apparatus purchase. The elec­ted Committee started to organize voluntary fund-raising campaign among the Club mem­bers and the apparatus was bought in Chemnitz in April 1897. A proposal was submitted to the Municipal Council and an annual subvention in the amount of 300 florins was approved for wear and tear and maintenance expenses. Demonstration of the apparatus, accompa­nied with a detailed lecture, took place on June 22, 1897. Ali the physicians from Rijeka, Opa­tija, Volosko and the Croatian coastal region were invited and 22 of them attended the presentation. Another important date was November 17, 1899, when the roentgen apparatus was handed out by the Club and installed in the Holy Spirit Town Hospital. Namely, the Hospital suggested the Club to lend the apparatus to it against a certain fee, and the Club Committee made a hire contract for 50 florins annual compensa­tion. Using its funds, the Committee took care of adaptations of the aparatus to electric current to avoid the use of battery-powered system. The apparatus was returned to Committee and Max Kohl was asked to perform the required modifications. Having been taken to Rijeka, it was assembled in Bacteriological laboratory of the aforementioned hospital together with ma­nual for Dr. Izidor Garafolo. Six years later, on November 10, 1908, the Hospital Council and the management asked the town authorities to approve a purchase of another apparatus, and the request was solved positively. Siemens-Halske firm from Budapest agreed to payment one year after delivery in the amount of 5,999.73 crowns, other expenses 1,291.52 crowns, totalling to 7,291.25 crowns. Probably they had not been experienced in handling the machine, for the hospital manage­ment submitted the town authorities another request for the new apparatus on December 23, 1914, because the previous one was completely ruined, and by the opinion of technical experts irreparable. According to ample documentation used by the authors of the book "Ars aesculapii -sup­plements to the history of health culture in Rijeka and Croatian coast", my teacher and predecessor retired in 1985, longtime head of the Institute of Radiology in Rijeka and full tirne Professor at Medica! Faculty Rijeka Dr. Marjan Matejcic and his wife Dr. Radmila Matejcic, full-time professor at Teacher-Training Faculty in Rijeka, whose work was used as the source of the presented historical review on the deve­lopment of radiology in Rijeka, the following could be deduced: Prof. Dr. Petar Salcher has been considered the first roentgenographer in Rijeka and Prof. Salvatore Bratanic and Milan Gorup the first roentgenological technicians, whereas Dr. Izi­dor Garafolo should be unofficially regarded as the first "radiologist" in Rijeka. Naturally, the Committee president baron Juraj Vranyczany played very significant role in obtaining a roentgen apparatus for Rijeka among the first Central European towns already by the end of the 19th century when Wilhelm Conrad Roentgen discovered x-rays. References l. Matejcic M. Pokusi dra Petra Salchera s rendgen­skim zrakama u Rijeci 1896. godine. Medicina 1974; 11-116. 2. Matejcic M. Pokusi dra Petra Salchera s rendgen­skim zrakama u Rijeci 1896. godine i prvi rendgen­ski aparat u rijeckoj bolnici »Sv. Duh«. In: Radmila i Marijan Matejcic: Ars Aesculapii -prilozi za povijest zdravstvene kulture Rijeke i Hrvatskog primorja. Rijeka, 1982; 117-33. Radio/ Oncol 1992; 26: 167-8. The 6th postgraduate course on thoracic radiology Jone 11-13, 1992, Salzburg, Austria The course was organized by the Department of Radiology, John Hopkins University in Bal­timore (Maryland, USA), and the Eberhard Karl University in Tuebingen (Germany), un­der the auspices of the European Society of Radiology. Half the invited speakers were from the Unit­ed States. The course took place in the Con­gress Centre and was attended by more than 500 participants. Thirty-minute lectures follo­wed by a discussion were intended to present the main diagnostic methods used in the up-to­date radiology of the chest organs. The intro­ductory lectures dealt with classical radiography in P-A and lateral projection, followed by CT, MR, radionuclide and interventional diagno­stics and also by the evaluation of surgical treatment of lung and esophageal cancer. When associated with good technique and correct interpretation, classical radiography in P-A and laterni projection is considered to be the basic examination providing a sufficiently good image of most pathology always when unnecessary exposure to X-rays should be avo­ided. As in children the presence of overt pathological processes in the shadow of the heart or mediastinum is less probable, lateral view imaging can be omited if the P-A radio­gram is unsuspicious and there is no clinical symptoms requiring a lateral view. As expected, most of the tirne and program was dedicated to CT. Technically improved HRCT (high resolution CT) enables imaging of 1-3 mm thick sections of the chest on which lesions 250-300 microns of size can be detected. Thus, pathological changes associated with di­seases of the pulmonary interstice, bronchiecta­sies and emphysema can be detected and their clinical and laboratory properties explained even when the chest radiograms are normal. The authors claimed that, using this method, a fairly reliable differentiation between carcino­matous lymphangiosis, interstitial fibrosis and diffuse sarcoidosis is possible, which renders biopsy often unnecesary. U nfortunately, the precise CT images were mostly shown in corre­lation with histologic samples of the same chan­ges, and not also with classical radiograms; being used to establishing most pathology from radiograms, we found this to be a considerable drawback. It has been easy to note the prevail­ing tendency to avoid biopsy and microscopic diagnosis by means of accurate CT findings, the approach which is in western countries apparen­tly considered cheaper and simpler, whereas here it is just the opposite: with only 3 CT machines available for the whole Slovenia, it is often faster, more rational and also economical to perform a biopsy rather than waste tirne in waiting for CT. Perhaps, by purchase of new CT machines the situation will change also in our country. A special lecture was dedicated to pulmonary changes in AIDS. Thus, such changes were established in as many as 60 % of AIDS pa­tients. They appear as a result of pulmonary parenchyme infections (most frequently caused by Pneumocystis carinii and mycobacteria), lymph node conditions (reactive hyperplasias and lymphomas), neoplasms (Kaposi's sarcoma, metastases) as well as premature emphysema and changes associated with drug abuse. PCP (Pneumocystis carinii pneumonia) was found in more than 85 % of patients with AIDS, and is generally the first sign of the disease. In these cases CT is much more reliable than classical radiography which failed to evidence the disease in 5-10 % . The signs of prema ture aging seen in AIDS patients manifest themselves in cystic pulmonary changes which often lead to a spon­taneous pneumothorax. Frequent exacerbations of tuberculosis and the consequences of pulmo­ 168 Debevec M, nary embolisms result in additional pulmonary changes in patients with this disease. As we expect to obtain magnetic resonance imaging (MR) facilities in Ljubljana next year, we found the comparison of CT and MR possi­bilities very interesting. Thus, in the detennina­tion of lung cancer stage, MR proved more accurate in the evaluation of soft tissue of the mediastinal organs such as large vessels, eso­phagus, pericardium and the external part of the tracheal bifurcation, whereas it showed no advantages over CT in the evaluation of media­stinal lymph node involvement. In the diagnosis of primary lung tumors both examinations have proved equally accurate although for the eva­luation of hilar lymph nodes MR is more effect­ive. Therefore, the \atter investigation is indica­ted in Pancoast's tumors, suspicious hilar lymph nodes, unexplained involvement of the thoracic wall in peripheral tumors, and in the cases of enlarged suprarenal gland which are in two thirds due to benign changes. As to the eva\ua­tion of mediastinal lymph nodes, the following procedures are suggested: in nodes up to 1 cm of size -thoracotomy, and in nodes larger than 1 cm -mediastinoscopy, and provided that the site allows for it, transbronchial punction biop­sy. In general, in the evaluation of mediastinal lymph nodes both CT and MR yield equal rate of sensitivity and specificity, i. e. they are suc­cessful in approximately 2/3 cases. Otherwise, 17 % of enlarged mediastinal lymph nodes are found to be free of metastases. A combination of CT and MR does not improve the diagnostic reliability in pulmonary carcinoma. In congenital diseases of the lung, such as pulmonary sequestration, cysts, emphysema, arterio-venous malformations and scimitar syn­drome, MR has some advantages over CT. Central pulmonary carcinomas bleed more frequently from the bronchial arteries, whereas peripheral ones generally bleed from the pulmo­nary arteries. Hemophthysis can be stopped by Report the embolisation of a corresponding bronchial artery. The dilatation of collaterals from other arteries, which occurs after embolisation, gene­rally does not lead to necrosis. Nevertheless, complications due to fistulae, as well as spina! ischemia with resulting neurological disorders and even embolisms of the aorta and lower extremities are also possible. Considering the small number of embolisations performed so far, this type of hemophthysis treatment cer­tainly cannot be regarded as a part of routine therapy. With the exception of perfusion and ventila­tion scintigraphy in the diagnosis of embolism or evaluation of pulmonary function, the pre­sented radionuclide examinations of the lung and mediastinum, though interesting, are of no particular value for the selection of therapy. Among other things, they showed increased uptake of gallium-67 in non-small celi lung cancer -the pathophysiology of this entity has not been fully explained yet -(sensitivity 91 % ) , but not in small celi cancer!? In lymphomas gallium is supposed to be useful for the asses­sment of tumor vitality. In the surgery for lung cancer, attention is paid to the thoracoscopic removal of smaller superficial tumors in patients with contraindica­tions for thoracotomy. The course proved useful so for the diagnostic radiologists as well as for clinicians. The former could follow the advances in CT and MR diag­nostics, whereas the latter could find this know­ledge helpful in selecting indications for indivi­dual investigations. We believe that by the access to new HRCT and MR units which will be available in the University Clinical Center in Ljubljana next year we shall get the opportu­nity to make use of the knowledge acquired at the course. Prof. Miha Debevec MD, PhD. Institute of Oncology Ljubljana Radio/ Oncol 1992; 26: 169. Libri Oncologici Croatian J ournal of Oncology It has been 20 years since Prof. Padovan and his coworkers established the journal "Libri Oncologici" in 1972 in Zagreb. The journal covered the territory of former Yugoslavia. Its publishers were the Central Institute for Tu­mors and Allied Diseases in Zagreb, Croatian League Against Cancer, Pharmaceutical Com­pany "Pliva" Zagreb, and the Association of Yugoslav Cancerologists. The journal appeared quarterly and was managed by the Editorial Board and Prof. Predrag Keros, MD, as the editor-in-chief. There have been XX volumes published so far. The articles of both national and foreign authors covered ali fields of expe­rimental and clinical oncology and allied specia­li ties. After the Xth volume English has become the official language of the journal, so that papers could be published either in Croatian or Eng­lish. By recent geopolitical changes having ta­ken place in the territory of the former Yugo­slavia, i.e. by 1992, the journal continued to appear under the same title of "Libri Oncologi­ci", though with a new publisher: thus it has become the official journal of Croatian Oncolo­gists (Croatian Journal of Oncology). On that occasion a new editorial board was selected and Prof. Dr. Krsto Kolaric was appointed the editor-in-chief. It has been agreed that the change calls for a new scientific scope of the journal to be defined and its graphic design changed in accordance with modem styles. The editorial board will stick to its policy of covering the multimodal aspects of oncology, thus enabling the presence of both basic and clinical research in this field on an equal foot­ing. Our further aim is to encompass new allied fields such as immunology, genetics, molecular biology, biochemistry and others, in order to give the most comprehensive overview of the trends in present oncological research. Another new line in the editorial policy is also to strive that a larger number of foreign authors would be attracted to collaborate in the journal, which would enable its promotion beyond the national borders in the neighbouring European coun­tries. In order to help young perspective resear­chers to have their papers published without delay, the functioning of the editorial office will be organized so that the period from receipt of manuscript to its publication will not exceed 6-8 months, including the tirne needed for double peer review. Summarizing, the main objective of our journal is to promote a compre­hensive and fruitful scientific collaboration at the international leve!. The presented issue is therefore No. 1 of the XXIth volume of our journal with an up-to­dated contents and form. We leave it up to our readers to decide to what extents our new editorial policy will have been justified. Prof. Krsto Kolaric, MD, Editor-in-Chief of Libri Oncologici Radio! Oncol 1992; 26: 170-1. Notices Notices submitted for publication should contain a mailing address and phone number of a contact person or department. Reconstruction in surgical oncology The congress will take place in Genova, Italy, Decem­ber 3-5, 1992. Contact Congress Management Service, Italiana Congressi, Via Bensa, 2/6 -16124 Genova, Italy; or call +3910 202541 or 280924. Fax: +3910 299382. Breast cancer 15th The Annual San Antonio symposium will be offered in Texas, USA, December 9-10, 1992. Contact Cancer Therapy and Research Center, 4450 Medica! Drive, San Antonio, TX 78229, USA. Celi biology The regular staff meetings at the Netherlands Cancer Institute will be offered in Amsterdam, The Nether­lands, December 14, 1992. Contact Ms. P. I. W. Sobels, The Netherlands Can­cer Institute; or call + 31 20 5121970. Nausea and vomiting The seminar will be organised by European Cancer Centre and held in Amsterdam, The Netherlands, December 15, 1992. Contact Robert van Bokhoven, IKA; or call +3120 617 2903. lmmunology The 5th annual meeting on the "Current Status and Future Directions of Immunoconjugates -Diagnostic and Therapeutic Applications in Benign and Malignant Disorders" will be offered in Key Biscayne, Florida, USA, January 14-17, 1993. Contact Lidia Gutierrez, Division of Continuing Medica! Education, University of Miami School of Medicine; or call + 1305 547 6716. Fax: + 1 305 547 5613. Oncology 3th The European winter oncology conference (E­WOC) will take place in Meribel, France, January 23-29, 1993. Contact Federation of European Cancer Societies, University Hospital St. Rafael, Radiotherapy Depar­tment, Capucijnenvoer 35, 3000 Leuven, Belgium; or call +3216 21-22-15. Fax: +3216 212241. Anti-cancer chemotherapy The 4th international congress will be held in Paris, France, February 2-5, 1993. Contact Prof. David Khayat, 4th International Con­gress on Anti-cancer Chemotherapy, SOMPS-Hopital de la Pitie-Salpetriere, 47, Bd de I'Hopital, 75651 Paris Cedex 13-France. Breast cancer The EUSOMA consensus conference on screening methology and management of occult breast carcino­mas will take pJace in Paris, France, February 4-5, 1993. Contact EUSOMA secretariat, Piazza Tricolore 2, 20129 Milan, Italy; or call + 39 2 780488. Fax: +39 2 781019. Notices 171 Colorectal cancer The conference "Towards Reducing the lncidence of Colorectal Cancer: The Role of Inheritance and Diet" will be offered in Auckland, New Zealand, February 16-19, 1993. Contact Dr. L. R. Ferguson, Conference Convenor, Cancer Society, P O Box 1724 , Auckland, New Zea­land. Oncology The teaching course on "The importance of Oxygen and other Micro-environmental factors in clinical chemotherapy and radiotherapy of cancer" will be held in Los Gigantes, Tenerife, February 22-24, 1993. Contact Dr. A. Yillar Rodriguez, Manuel Garcia Calveras 27, 38008 Santa Cruz de Tenerife, Spain. Supportive care in cancer The 4 th international symposium will take place in St Gallen, Switzerland, February 24-27, 1993. Contact Mrs. Beatrice Nair, Conference Manager SUP-93, c/0 Prof. H. J. Senn, Dept Medicine C (Onco­logy), Kantonsspital, CH-9007 St Gallen, Switzerland. Fax: +4 171256 805. AIDS-related tumours The ESO seminar will be held in Venice, Italy, March 4-5, 1993. Contact European School of Oncology, Via Yene­zian, 1820133 Milan, ltaly; or call +392 706 35923 or 2364283. Fax: +3922664662. Medica! oncology The ESO training course for the Balkans and Middle East will take place in Athens, Greece, March 4-6, 1993. Contact European School of Oncology -Athens Office, 2 Adrianiu St. & Papada St., 11825 Athens, Greece; or call +30 164 96620. Fax: +30 16 924 372. Oncology The ESO seminar "Minimal residual disease: detection and management" will take place in Yenice, Italy, March 26-27, 1993. Contact European School of Oncology, Via Yene­zian, 1820133 Milan, ltaly; or call +392 706 35923 or 2364283. Fax: +3922664662. Brachyradiotherapy The ESTRO teaching course will take place in Athens, Greece, March 28 -April 1, 1993. Contact the ESTRO Secretariat -University Hospi­tal St. Rafael, Radiotherapy Department, Capucijnen­voer 35, 3000 Leuven, Belgium; or call +32 16 21-22­13. Fax: +32 16 212228. Medica! oncology The postgratuate course will be organised by European Cancer Centre and held in Amsterdam, The Nether­ lands, March 28 -April 3, 1993. Contact Robert van Bokhoven, IKA; or call +3120 6172903. Melanoma The 3th international conference on melanoma will be held in Yenice, Italy, March 31 -April 3, 1993. Contact European School of Oncology, Via Yene­zian, 18 20133 Milan, Italy; or call + 39 2 706 35923 or 2364283. Fax: +3922664662. SIEMENS SOMATOM AR.T SIC 212 Ganzkorper-Computertomograph l. 0J I® tablets 400 mg Ab a kt a . ampoules 400 mg (pefloxacin) A new potent drug against infections • May be given orally and parenterally • Effecive in life-threatening infections caused by nosocomial strains resistant to many drugs • May be given to patients hypersensitive to penicillins and cephalosporins • lts favourable pharmacokinetic properties allow twice-a-day dosage • 1s very well tolerated Contraindications Pefloxacin is contraindicated in patients with known hypersensitivity to quinolones, in preg­nant women, nursing mothers, children under 15 years of age, and patients with inborn glucose-6-phosphate dehydrogenase deficiency. Precautions During pefloxacin therapy exposure to strong sunlight should be avoided because of the risk of photosensitivity reactions. In patients with a severe liver disorder dosage of pefloxa­cin should be adjusted. Side effects Gastro-intestinal disturbances, muscle and/or connective tissue pains, photosensitivity reactions, neurologic disturbances (headache, insomnia), and thrombocytopenia (at doses of 1600 mg daily) may occur. Dosage and administration The average daily dosage for adults and children over 15 years of age is 800 mg. Oral: 1 tablet twice daily after meals. Parenteral: the content of 1 ampoule 400 mg diluted in 250 ml of 5 % glucose as a slow 1-hour infusion twice daily. The maximum daily dosage is 8 mg of pefloxacin per kg body­weight. In severe hepatic insufficiency pefloxacin is administered only once daily (jaundice), once every 36 hours (ascites), and once every 48 hours (jaundice and ascites). ®lek Pharmaceutical and Chemical Works Ljubljana Klimicin ® (Clindamycin) Klimicin is an effective It stimulates the action bactericidal or of polymorphonuclear bacteriostatic as leukocytes (PMN) evidenced by the principal factors in MIC/MBC ratio. host immune system. 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The posibility of pseudo­ membranous colitis must be ruled out. @ Lek, Pharmaceutical and Chemical works Ljubljana Bacteroides spp. (including Bacteroides fragilis) Fusobacterium spp. Propionibacterium Eubacterium Actinomyces spp. Peptococcus spp. Peptostreptococcus spp. Clostridium perfringens © Eastman Kodak Company, 1990 Kodak systems provide dependable performance for advanced diagnostic imaging. Our qua/ity components are made to work together from exposure to viewbox. Kodak X-Omat processors are the most respected in the field. Kodak X-Omatic cassettes are known the world over for unexcelled screen-film contact and dura­bility. Kodak multiloaders have earned an enviable reputation for reliability. The Kodak Ektascan laser printer is changing the look of digital imaging. The list goes on. There are quality Kodak products throughout the imaging chain. Equally important, they are made to work together to achieve remarkable performance and diagnostic quality. 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Prestilix DRS Advantx AFM Vectra VMX GENERAL ELECTRIC CGR: Zagreb, Croatia Tei /041) 43 71 59-Fax: /041) 42 55 12 ® SOLVOLAN(ambroksol) tablete, sirup nov sinteticni mukolitik in bronhosekretolitik • uravnava intracelularno patološko spremenjeno sestavo izlocka v dihalih • stimulira nastajanje in izlocanje surfaktanta iz celic pljucne strukture • povecuje baktericidnost alveolarnih makrofagov • zmanjšuje adhezijo bakterij in levkocitov na sluznico dihalnih poti • sprošca zastojni in žilavi izlocek s stene bronhijev in olajšuje izkašljevanje • odstranjuje bronhialni izlocek s spodbujanjem mukociliarnega prenosnega sistema in neposrednim vplivom na delo cilij • zmanjšuje viskoznost bronhialne sluzi • ublažuje neproduktivni kašelj • olajšuje dihanje Oprema 20 tablet 100 ml sirupa Podrobnejše informacije in literaturo dobite pri proizvajalcu. ... KRK. tovarna zdravil, p.o., Novo mesto Il®.rnftmru LESNINA ZDRUŽENA PODJETJA ZA TRGOVINO, INŽENIRING IN PROIZVODNJO, n.sub.o. OSEBNA IZKAZNICA LESNINE JE: -ena najvecjih in najstarejših trgovskih organizacij v lesni stroki z dolgo­letno tradicijo, saj posluje že vec kot štirideset let -organizacija, ki prodaja pohištvo, notranjo opremo ter gradbeni material -organizacija, ki opravlja celoten inženiring v notranji opremi in opremi lesno predelovalnih tovarn doma in v tujini -proizvajalec ekskluzivnega pohištva, pohištva po meri in druge notranje opreme ter proizvodov iz aluminija -organizacija, ki združuje enajst podjetij ter tri družbe -izvaža v štirideset držav po vseh celinah in je tretji najvecji izvoznik pohištva -ima sedem lastnih in mešanih podjetij ter predstavništev v tujini in sedem montažnic pohištva v ZDA -organizacija, ki ima financno poslovanje urejeno v lastni interni banki -organizacija, ki zaposluje 2.100 ljudi. TOSAMA Tovarna sanitetnega materiala p.o. 6123Q Domžale p.p. 128 Vir, Saranoviceva 35 telefon: (061) 714-611 telefax: (061) 714-660 telex: 39-804 IZDELUJE: SANITETNI PROGRAM -tkane, rezane, elasticne povoje -mavcne in sadrona povoje -sanitetno mrežo Virfix -konfekcionirano gazo -konfekcionirano vato -celulozno vato in izdelke -obliže -sanitetne torbice, omarice -avtomobilske in motorske apoteke PROGRAM IZDELKOV ZA OSEBNO HIGIENO -higienski vložki VIR -higienski tamponi VIRT AMP -higiensko in cik-cak vato -Jasmin vato -Jasmin blazinice -bebi palcke OTROŠKI PROGRAM -tekstilne plenice -nocne plenice TOSAMA -hlacne plenice SAMO Super -bebi plenicne predloge -povijalne rutice -zašcitne hlacke PROGRAM MEDICINSKE PLASTIKE -Virko! vrecke -urinske vrecke VIRTEKS PROGRAM -posteljno perilo -zdravniške maske -kape -bolniške, ortopedske, zdravniške -operacijski plašci, halje, predpasniki -prevleke za obuvala -rute za operirance -operacijska pregrinjala INKO PROGRAM -Inko podloge -Inko povijalne rute -Inko hlacke -podloge za bolnike PROGRAM IZDELKOV ZA DOM -vecnamenska krpa Bistrica -polirna vata -vrteks -vrtnarska vlaknovina 5 s::I L U !5i LJUBLJANA D. D. 61000 LJUBLJANA, MAŠERA-SPASICEVA ul. 10 Telefoni: n.c. (061) 181-144 -direktor: 182-069 -prodaja: 181-031, 181-130, 182-001, 181-041 -Fax: 181-022 OSKRBUJE lekarne, bolnišnice, zdravstvene domove ter druge ustanove in podjetja s farmacevtskimi, medicinskimi in drugimi proizvodi domacih proizvajalcev, s proizvodi tujih proizvajalcev pa s pomocjo lastne zunanjetrgovinske službe. Proizvaja: ALLIVIT PLUS® Kapsule cesna z dodatkom zdravilnih zelišc. Prodajna in dostavna služba posluje vsak dan neprekinjeno od 7. do 16. ure, razen sobote. !:SANOLABOR IZVOZNO UVOZNO PODJETJE ZA PROMET Z MEDICINSKIMI INSTRUMENTI, APARATI, OPREMO ZA BOLNICE, LABORATORIJE IN LEKARNE LJUBLJANA, Cigaletova 9 Telefon: (061) 317-355 Telex: 31-668 sanlab yu Telefax: 325-395 Iz prodajnega programa trgovine na debelo nudimo široko izbiro domacega in uvože­nega blaga po konkurencnih cenah in sicer: -rentgenske filme in kemikalije pro­izvajalcev »Fotokemika«, »KODAK«, »3 M -TRIMAX«, »AGFA GEVAERT« in drugih ter kontrastna sredstva firme »NICHOLAS«, -medicinske instrumente, specialno medi­cinsko in sanitetno blago, potrošno blago za enkratno uporabo, -medicinske aparate in rezervne dele zanje ter drugo bolniško opremo, -tekstilne izdelke, konfekcijo in obutev za potrebe zdravstvenih, proizvodnih in var­stvenih organizacij, Predstavništvo: ZAGREB, Koturaška 73 Telefon: (041) 614-877 Telefax: (041) 513-385 -laboratorijske aparate, opremo, laborato­rijsko steklovino, reagente, kemikalije in pribor, -aparate, instrumente in potrošno blago za zobozdravstvo V Ljubljani imamo dve prodajalni: -na Cigaletovi 9 prodajamo izdelke iz asor­timana trgovine na debelo, s posebnim poudarkom na izdelkih za nego bolnikov, ortopedskih pripomockih in ostalemu blagu za široko potrošnjo vsak dan od 9h do 18h, ob sobotah od 9h do 13h , -v prodajalni na Njegoševi 15 nudimo opremo, instrumente in potrošne mate­riale za zobozdravstvene ordinacije in tehnike vsak dan od gh do 15h, ob sobo­tah od 8h do 12h . The publication of the journal is subsidized by the Ministry of Science and Technology of the Republic Slovenia. CONTRIBUTIONS OF INSTITUTIONS: Inštitut za diagnosticno in intervencijsko radiologijo, UKC Ljubljana Klinika za otorinolaringologijo in maksilofacialno kirurgijo, UKC Ljubljana Klinicki zavod za dijagnosticku i interventno radiologijo, KBC Rebro, Zagreb Onkološki inštitut, Ljubljana Organizacijski odbor Desetog znanstvenog skopa Hrvatskog društva radiologa (Varaždin, 1992) DONATORS ANO ADVERTISERS: ACTIV A International S.r .I., Trieste, Italy AGOREST S.r.I., Gorizia, Italy ANGIOMED Karlsruhe, Germany General Electric -CGR Representative Otlice Zagreb, Croatia KRKA p.o. Novo mesto, Slovenia LECLERC & CO Schaffhausen, Switzerland LEK d.d. Ljubljana, Slovenia LESNINA INTERNA BANKA d.o.o. Ljubljana, Slovenia MEDITRADE-KODAK, Ljubljana, Slovenia SALUS d.d. Ljubljana, Slovenia SANOLABOR p.o. Ljubljana, Slovenia SIEMENS d.o.o., 'Ljublj.na, Slovenia TOSAMA p.o. Domžale, Slovenia Radio/ Oncol 1992; 26: 188. Instructions The journal Radiology and Oncology publishes ori­ginal scientific papers, professional papers, review ar­ticles, case reports and varia (reviews, short communi­cations, professional information, ect.) pertinent to diagnostic and interventional radiology, computerised tomography, magnetic resonance, nuclear medicine, radiotherapy, clinical and experimental oncology, ra­diobiology, radiophysics and radiation protection. Submission of manuscript to Editorial Board implies that the paper has not been published or submitted for publication elsewhere: the authors are responsible for ali statements in their papers. Accepted articles become the property of the journal and therefore cannot be published elsewhere without written permis­sion from the Editorial Board. Manuscripts written in English should be sent to the Editorial Office: Radiology and Oncology, Institute of Oncology, Vrazov trg 4, 61000 Ljubljana, Slovenia; Phone; + 38 61314 970; Fax: + 38 61329177. Radiology and Oncology will consider manuscripts prepared according to the Vancouver Agreement (N Engl .-Med 1991; 324: 424-8.; BMJ 1991; 302: 6772.). Ali articles are subjected to editorial review and review by two independent referees selected by the Editorial Board. Manuscripts which do not comply with the technical requirements stated here will be returned to the authors for correction before the review of the referees. Rejected manuscripts are gene­rally returned to authors, however, the journal cannot be held responsible for their loss. The Editorial Board reserves the right to require from the authors to make appropriate changes in the content as well as gramma­tical and stylistic corrections when necessary. The expenses of additional editorial work and requests for reprints will be charged to the authors. General instructions: Type the manuscript double spa­ced on one side with a 4 cm margin at the top and left hand side of the sheet. Write the paper in grammati­cally and stylistically correct language. Avoid abbrevia­tions unless previously explained. The technical data should confirm to the SI system. The manuscript, including the references may not exceed 15 typewritten pages, and the number of figures and tables is limited to 4. If appropriate, organise the text so that it includes: Introduction, Material and methods, Results and Discussion. Exceptionally, the results and discus­sion can be combined in a single section. Start each section on a new page and number these consecutively with Arabic numerals. Authors are encouraged to submit their contributions besides three typewritten copies also on diskettes (5 1/4") in standard ASCI format. to authors First page: -name and family name of ali authors, -a brief and specific title avoiding abbreviations and colloquialisms, -complete address of institution for each author, -in the abstract of not more than 200 words cover the main factual points of the article, and illustrate them with the most relevant data, so that the reader may quickly obtain a general view of the material. lntroduction is a brief and concise section stating the purpose of the article in relation to other already published papers on the same subjects. Do not presen! extensive reviews of the literature. Material and methods should provide enough informa­ tion to enable experiments to be repeated. Write the Results clearly and concisely and avoid repeating the data in the tables and figures. Discussion should explain the results, and not simply repeat them, interpret their significance and draw conclusions. Graphic material (figures and tables). Each item should be sent in triplicate, one of them marked original for publication. Only high-contrast glossy prints will be accepted. Line drawings, graphs and charts should be done professionally in lndian ink. Ali lettering must be legible after reduction to column size. In photo­ graphs mask the identities of patients. Labe! the figures in pencil on the back indicating author's name, the first few words of the title and figure number: indicate the top with and arrow. Write legend to figures and illustrations on a separate sheet of paper. Omit vertical lines in tables and write the next to tables overhead. Labe! the tables on their reverse side. References should be taped in accordance with Van­couver style, double spaced on a separate sheet of' paper. Number the references in the order in which they appear in the text and quote their corresponding numbers in the text. Following are some examples of references from articles, books and book chapters: l. Dent RG, Cole P. In vitro maturation of monocy­tes in squamous carcinoma of the lung. Br J Cancer 1981; 43: 486-95. 2. Chapman S, Nakielny R. A guide to radiological procedures. London: Bailliere Tindall, 1986. 3. Evans R, Alexander P. Mechanisms of extracellu­lar killing of nucleated mammalian cells by macropha­ges. In: Nelson DS ed. lmmunobiology of macrophage New York: Academic Press, 1976: 45-74. For reprint information in Norih America Contact: fnlernational reprint Corporation 968 Admiral Callag­han Lane, # 268 P. O. Box 12004, Vallejo, CA 94590, Tel.: (707) 553 9230, Fax: (707) 552 9524. INTERNATIONAL Y our Partner in Radiology ACTIV A International Sri Tel. 040-212856 Via di Prosecco, 2 Telefax 040-213493 34016 Opicina -Trieste Telex 460250 I ltaly