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Antibiotic ceftriaxone enhances the expression of GLT1 glutamate membrane transporter in the brain and decreases the availability of synaptic glutamate. To investigate whether this anti glutamate effect of ceftriaxone could modulate anxiety, we used elevated plus maze (EPM) and elevated T maze (ETM) tests. EPM is a plus sign shape elevated 60 cm from the floor with two opposite enclosed arms (50x10 cm with 30 cm high walls) vertical to two opposite open arms (50x10 cm) and intersection zone (10x10 cm). The individual rat was left in the intersection zone to investigate EPM for 5 minutes. Avoidance of open, unsafe arms in EPM suggests anxiety. ETM is the same as EPM with one blocked enclosed arm. ETM measure avoidance behaviour in 4 subsequent avoidance sessions and escape behaviour in 4 escape sessions. In the avoidance ETM session, the rat starts at the distal end of the enclosed arms. But in the escape ETM session at the distal end of the open arms. Both avoidance and escape individual sessions last 5 minutes. We assigned 21 or 22 male Wistar rats for ETM or EPM in groups treated with ceftriaxone (200 mg/kg IP., 1 x daily in 9 days) or saline (5mL/kg IP.). Behavioural data were collected and analysed by camera and video tracking software Any maze 4.82. Results revealed that ceftriaxone significantly increases exploration behaviour (number of head dipping) in unsafe zones of EPM (open arms and intersection zone) without influencing avoidance, escape, locomotion or defensive behaviour in EPM or ETM.

To find out whether different testing periods during an active (dark) phase of the day might modulate anxiety-like behaviour in an elevated C maze (ECM), we assigned 30 male Wistar rats to groups of 10 animals tested in ECM during the morning (10-12 hrs), early afternoon (14-16 hrs) or late afternoon (18-20 hrs). ECM have the shape of the letter C, it is 80 cm elevated from the floor, enclosed in the middle third (22 cm long, 15 cm wide) with two side walls of 30 cm in height. Two-thirds of the maze (each 22 x15 cm) are open, without walls. For testing, individual rats were allowed to freely explore ECM for 5 minutes. Behaviour data were collected and analysed by camera and video tracking software Any maze 4.82. Results showed that independent of testing time, rats had a significantly higher number of entrances, spend more time and travel a longer distance in the safe, enclosed zone of ECM as compared to unsafe open zones. Also, we found no differences in horizontal or vertical rat locomotion in ECM or ECM zones. But freezing time (defensive behaviour) was longer in the morning and early afternoon than in the late afternoon for ECM. In the enclosed ECM zone, the number of faecal boli (a sign of emotionality), the number of head dipping (exploration) and the number of entrances (avoidance) were lower during the morning and early afternoon testing period. In conclusion, testing of Wistar rats during different periods within the active (dark) phase of the day might modulate anxiety-like behaviour in ECM.

To investigate whether Wistar rats habituate to predator stress test based on cat odour, we assigned 12 Wistar male rats to the group exposed to cat bedding dirtied with cat excretions (cat odour) and to the group exposed to clear, unused cat bedding (false cat odour). Animals were tested in a square arena virtually divided by video tracking software in an unsafe, smaller zone containing a beaker filled with cat odour and a safe, large area with a cup filled with false cat odour. Individual rats could freely explore the arena for 10 minutes in habituation (it was empty), test (scants were in it) and retest session (same as test session). During the habituation session, we didn’t find differences between experimental groups in the behavioural data collected. But, during the test session, the number of contacts with the beakers and rearing decreased in the cat odour group, while the number of stretches increased in this group compared to the false cat odour group. Also, the number of entries and time spent in the unsafe zone declined, and the total distance travelled in the arena enlarged in rats exposed to cat odour compared to rats exposed to the false scent. Behavioural and locomotor differences described above vanish during the retest session. Stretch attending number was an exception. In rats exposed to cat odour, stretches still increased. Here we demonstrate that a predator stress test based on cat odour is functional in our hands and susceptible to one trial habituation.

Cilj: Cilj istraživanja je prikazati epidemiološke, kliničke i laboratorijske karakteristike B.henselae infekcije u djece liječene u Klinici za infektivne bolesti “Dr. Fran Mihaljević”, Zagreb, u razdoblju od siječnja 2014. do lipnja 2019. godine. Materijali i metode: Retrospektivno smo istražili kliničke karakteristike, epidemiologiju i laboratorijske parametre u bolesnika mlađih od 18 godina kod kojih je infekcija potvrđena indirektinim imunoflorescentnim testom za IgM i IgG na B.henselae ili detekcijom B.henselae lančanom reakcijom polimerazom (PCR) iz punktata limfnog čvora. Rezultati: Od ukupno 104 bolesnika, 47 (45, 1%) je bilo ženskog i 57 (54, 8%) muškog spola. Medijan dobi iznosio je 9, 7 godina (raspon, 1, 1 do 17, 3 godina). Kontakt s mačkom zabilježen je u 101 bolesnika (97, 1%). Infekcija je potvrđena serološki u 87 (83, 6%), metodom PCR-a u 5 (4, 8%), a kombinacijom obje metode u 12 (11, 5%) bolesnika. Najčešća manifestacija infekcije bila je regionalna limfadenopatija u 92 (88, 4%) bolesnika, a slijede diseminirani oblik bolesti u 5 (4, 8%), neurološke manifestacije koje su uključivale encefalitis, meningoencefalitis ili encefalopatiju u 4 (3, 8%) i vrućica nepoznatog porijekla u 3 (2, 8%) bolesnika. U 53, 6% bolesnika limfadenopatija nije bila praćena vrućicom. U 12 (13%) bolesnika s limfadenopatijom došlo je do razvoja supurativne upale koja je potvrđena citološki. Uz limfadenopatiju u 5 bolesnika (5, 4%) uočena je hepatosplenomegalija te u jednog bolesnika (1, 08%) Parinaudov sindrom. Ukupan broj leukocita prosječno je iznosio 9, 9 x 109/L, dok je prosječna vrijednosti C-reaktivnog proteina bila 23, 02 mg/L. Liječenje azitomicinom provedeno je u 77 (74, 0%), a kombinacija azitromicina, rifampicina i doksiciklina u 11 (10, 5%) bolesnika. U 10 (9, 6%) bolesnika učinjena je drenaža limfnog čvora. U 100 (96, 1%) bolesnika došlo je do izlječenja. Zaključak: Infekcija B.henselae u djece najčešće je blaga bolest koja se manifestira regionalnom limfadenopatijom. Serologija i PCR metode su izbora za dijagnozu bolesti. Duljina liječenja i izbor terapije ovise o kliničkoj manifestaciji infekcije uz vrlo visoku stopu izlječenja.

In several models of anxiety-like behaviour sublines of WZ-5HT rats with extremely low levels of platelet serotonin (low-5HT subline) showed less anxious behaviour than rats with extremely high platelet serotonin (high-5HT subline). To further investigate phenotype differences among WZ-5HT sublines in the domain of anxiety, we compared high-5HT (n=9) with low-5HT male rats (n=15) for a total number of grooming and rearing episodes during 10 minutes of the open field test and for the incidence to appear on rims of the open-top home cage during 5 minutes of the emergence test. Rats were tested in three subsequent sessions. In comparison to high 5HT rats, low-5HT rats had a significantly lower number of grooming episodes during all open field test sessions (p

In our new experimental model of cervical stenosis without inflammation we have tested hypothesis that cranio-spinal communication impairment could lead to hydrocephalus development. Spinal and cranial cerebrospinal fluid (CSF) space separation was obtained with positioning of plastic semiring in epidural space at C2 level in cats. Brain ventricles planimetry, and CSF pressure recording in lateral ventricle (LV) and lumbar subarachnoid space (LSS) were performed in acute and subchronic experiments. In all experiments opening CSF pressures were normal. However, in acute experiments, an infusion of artificial CSF into the LV led to increase of CSF pressure and significant gradient pressure development between LV and LSS due to limited pressure transmission. After 3 or 6 weeks spinal cord atrophy was observed at the site of cervical stenosis, and pressure transmission from LV to LSS was improved as a consequence of spinal tissue atrophy. Planimetry of both the coronal brain slices and the ventricles’ surface showed that control ventricular surface was 0.6 ± 0.1% (n = 5), and 1.6 ± 0.2% (n = 4) in animals with subchronic cervical stenosis (P < 0.002). These results support the mentioned hypothesis claiming that CSF volume cranio-spinal displacement impairment could start pathophysiological processes leading to development of hydrocephalus.

Svrha studije je bila procijeniti rizik nastanka urolitijaze u djece liječene ceftriaksonom. Retrospektivno je analizirano 238-ero djece s cistopijelonefritisom, liječene u 2011. godini, ceftriaksonom u standardnoj dozi od 60 mg/kg/dan kroz 10 dana. Slikovnom obradom u 74-ero djece nađene su anomalije mokraćnog sustava, od čega u njih 66-ero vezikoureteralni refluks, a u 7- ero hidronefroza. Ni u jednog djeteta nije nađena urolitijaza. Kliničkim praćenjem kroz mjesec dana nije bilo kliničkih i/ili laboratorijskih indirektnih znakova urolitijaze. Može se zaključiti da je liječenje ceftriaksonom u standardnoj dozi i dužini trajanja sigurno. Oprez je nužan ako su potrebne više doze i/ili produženo davanje. U tom slučaju preporučujemo pregled mokraćnog sustava i žučnjaka, probir na hiperkalciuriju i alkalinizaciju urina.

Neisseria meningitidis uzrokuje široki spektar infekcija od asimptomatskog kliconoštva do fulminantne sepse. Bitno je rano prepoznati i liječiti invazivne oblike bolesti kako bi se smanjio mortalitet i komplikacije. Kao rani dijagnostički pokazatelj invazivne bolesti navode se simptomi i znakovi sepse (bolovi u nogama, hladne okrajine, promjena boje kože). Osip se javlja kasnije i u početku ne mora biti hemoragičan. Odsutan je u značajnog broja bolesnika, pogotovo s meningitisom. Brzo započinjanje antimikrobnog i suportivnog liječenja ključno je za ishod. Antibiotici izbora su penicilin, ceftriakson ili cefotaksim. Odlučne suportivne mjere su izdašna nadoknada tekućine u šoku te mjere snižavanja intrakranijskog tlaka u meningitisu.

Akutni transverzni mijelitis (ATM) rijetka je bolest u dječjoj i adolescentnoj dobi. U SAD-u učestalost se procjenjuje oko 1-4 na 1 000 000 ljudi na godinu, ali ne postoji specifična procjena pedijatrijske incidencije. Bolest je klinički obilježena bilateralnom disfunkcijom kralježnične moždine, koja se očituje simetričnom mlohavom slabošću donjih ekstremiteta praćenom poremećajem osjeta i disfunkcijom mjehura. Opisali smo slučaj dječaka s tipičnim, longitudinalno ekstenzivnim ATM-om, naglim i promjenjivim nastupom paralize i progresijom unutar nekoliko sati. Dijagnoza je postavljena temeljem kliničke slike i tijeka bolesti, analizom cerebrospinalnog likvora (CSL), elektrofiziološkim pretragama kao i nalazom magnetske rezonancije (MR), koja je pokazala longitudinalno ekstenzivnu leziju medule spinalis. Unatoč rano uvedenim visokim dozama kortikosteroida u kombinaciji s plazmaferezom, njegov oporavak je spor i nakon 3 mjeseca ima još ozbiljne sekvele, te je i dalje na intenzivnoj fizikalnoj terapiji i kontinuirano će se pratiti.

Respiratorni sincicijski virus (RSV) uzrokuje akutne respiratorne infekcije u osoba svih dobnih skupina. Donji dišni putovi češće su zahvaćeni u dojenčadi i male djece s primoinfekcijom te u starijih i imunokompromitiranih, dok su u ostalih obično zahvaćeni samo gornji dišni putovi. Većina djece preboli primoinfekciju do druge godine života, dok su reinfekcije uobičajene tijekom života. RSV je najvažniji uzročnik infekcija donjega respiratornog trakta, a pogotovo bronhiolitisa, u dojenčadi. Karakteristična je sezonska pojavnost od kasne jeseni do ranoga proljeća s vrhuncem tijekom siječnja i veljače. RSV uzrokuje febrilni respiratorni katar, otitis, traheobronhitis, bronhiolitis i pneumoniju. Virus se može dokazati izolacijom iz respiratornih sekreta, a danas se rutinski koriste brzi testovi visoke osjetljivosti i specifičnosti kojima se dokazuje antigen. Liječenje je simptomatsko (adekvatna hidracija, antipireza, kisik, dekongestija nosne sluznice). U liječenju bronhiolitisa koriste se inhalacijski bronhodilatatori (albuterol, salbutamol, racemični epinefrin) i kortikosteroidi iako kliničke studije nisu dokazale njihovu djelotvornost. Ribavirin u obliku aerosola preporučuje se u djece kod koje očekujemo težu bolest. U dijela bolesnika nakon preboljele RSV infekcije zaostaje pojačana reaktivnost dišnih putova. Primjena palivizumaba, monoklonskog antitijela protiv RSV-a, indicirana je kao profilaksa kod djece s rizikom za tešku RSV infekciju. U našoj Klinici tijekom razdoblja od šest godina liječeno je 422 djece zbog bronhiolitisa uzrokovanog RSV-om. Dobna, spolna i sezonska raspodjela odgovaraju očekivanima. U 17 djece (4% hospitaliziranih) provođena je mehanička ventilacija, dok je jedno dijete umrlo (smrtnost 0, 24%). Više od polovice mehanički ventiliranih imalo je neki čimbenik rizika za težu bolest. Na varijacije u udjelu mehanički ventiliranih među hospitaliziranima vjerojatno utječe virulencija tipa virusa koji kruži u populaciji.

Background: Detection of enteroviral RNA (EV RNA) in the cerebrospinal fluid (CSF) of patients with aseptic meningitis (AM) by real-time polymerase-chain reaction (PCR) has become a part of routine diagnostic work-up. Rapid detection of EV RNA enables physicians to diagnose patients with EV AM within a clinically relevant time-frame (usually 24 h). Objective: The aim of this study was to describe the monthly distribution of EV RNA positive real-time PCR results obtained from CSF samples taken at the University Hospital for Infectious Diseases in Zagreb (UHID) during 2008 season. Materials and methods: Detection of EV RNA in the CSF was performed by using a standardized pan-enteroviral real-time PCR Cepheid ASR Enterovirus assay (Cepheid, USA). CSF samples were tested for the presence of EV RNA as a part of routine diagnostics in pediatric patients with presumed diagnosis of AM. Results: Children aged 7 days to 13 years (median 7.2 years) were included in the study. Enteroviral RNA was detected in 38 out of 95 CSF samples (40 %) tested. The first patients with PCR-positive results were detected in April (n=2) and May (n=2). Between June and September, a total of 15 PCR-positive results were obtained. The highest number of PCR-positive results within one month were obtained during October (n=11) which can be attributed to a localized outbreak. Conclusion: Pan-enteroviral PCR-positive results can be found throughout the majority of the year (between April and December). PCR Cepheid ASR Enterovirus assay is suitable for rapid detection of EV RNA in the CSF of patients with clinical symptoms and laboratory parameters suggestive of AM.

Nocardiosis is an opportunistic infection that might be associated with systemic lupus erythematosus (SLE). Lungs are the commonest site of infection, while central nervous system involvement is less common and is mostly due to haematogenous spread. We present a 13 year-old boy with SLE complicated with primary nocardial brain abscesses associated with meningitis which is extremely rare, especially in childhood. Three days after we started therapy of SLE with pulse doses of steroids, the patient presented with headache, seizures, diplopia, paresis of the right abducens nerve and anisocoria. CT scan of the brain revealed multiple abscesses. Laboratory findings indicated possible microbial infection but at first all attempts to detect the possible cause of infection were unsuccessful. Repeated stereotactic biopsy after three weeks of the symptoms onset revealed the presence of Nocardia spp. Owing to the poor tolerance and side-effects of antibiotics (trimethoprim/sulfamethoxazole and linezolid), the patient was treated successfully by two switching of one drug to another. The complete resolution of brain abscesses and meningitis followed two months after the therapy was started. The relapse did not occur after 24 months of follow-up and SLE went into complete remission, due to continuous steroid therapy which was gradually reduced. Conclusion: In this case, it was very difficult to diagnose cerebral nocardiosis, and the definitive diagnosis was made after second stereotactic biopsy. We managed nocardial brain abscesses with antibiotic therapy, but the relevant improvement of patient’ s condition was noticed after the second stereotactic biopsy when a large abscess was drained, so we suggest that for the treatment of cerebral nocardiosis only antibiotic therapy would not be enough.

Prikazali smo slučaj trogodišnje djevojčice s laboratorijski potvrđenim tuberkuloznim meningoencefalitisom i neurološkim komplikacijama koje su se razvile u kliničkom tijeku bolesti unatoč primjeni antituberkulozne terapije. Prikazana je CT evaluacija tuberkuloznog meningoencefalitisa koja je u početku bolesti pokazivala samo edem mozga, a u daljnjem tijeku i znakove meningitisa s hiperdenznim subarahnoidalnim bazalnim prostorima. U subakutnoj fazi CT-om su se verificirali ishemijski infarktni procesi bazalnih ganglija te znaci cerebritisa i ventrikulitisa. Neurokirurška intervencija pridonijela je regresiji hidrocefalusa, koji postaje normotenzijski uz razvoj frontalnih efuzija. Evaluacija tuberkuloznog meningoencefalitisa kompjuteriziranom tomografijom u Hrvatskoj je relativno rijetka te želimo kliničare podsjetiti na mogućnosti aplikacije CT-a i njegovu vrijednost u sličnim slučajevima.

The purpose of our retrospective 3-year study was to analyse and compare clinical and epidemiological characteristics in hospitalized patients older than 6 years with community-acquired pneumonia (CAP) caused by Chlamydia pneumoniae (87 patients) and Mycoplasma pneumoniae (147 patients). C. pneumoniae and M. pneumoniae infection was confirmed by serology. C. pneumoniae patients were older (42.12 vs. 24.64 years), and were less likely to have a cough, rhinitis, and hoarseness (P

McKittrick-Wheelock syndrome is a rare disorder caused by fluid and electrolyte hypersecretion from the rectal tumor. The most reported were villous adenomas. Dehydration with severe hyponatremia, hypokalemia, metabolic acidosis, acute renal failure and watery diarrhea is typical. The authors present a case of McKittrick-Wheelock syndrome due to rectal adenocarcinoma.

Experimental models of hydrocephalus.

In University Hospital for Infectious Diseases in Zagreb, in the period from 1988-1998, one hundred (100) children 0-6 years of age with Haemophilus influenzae type b (Hib) meningitis were treated (average 9 patients per year), so the presumed incidence of Hib meningitis in Zagreb and Zagreb county was 10-14/100000 children aged 0-6 years. The incidence of Hib meningitis in other European countries in prevaccination era was 15-26/100000 children aged 0-6 years, and in the United States and Canada 40-69/100000 children. Routine vaccination of children with conjugated Hib vaccines in the USA and some European countries resulted in high decrease in morbidity of Hib meningitis. In the last several years there was a possibility in Croatia for non-obligatory vaccination against Hib. Routine, obligatory vaccination against Hib for children in Croatia started on January 1st, 2002. Because of possible non-obligatory vaccination against Hib in the last few years, we expected a graduate decrease in the incidence of Hib meningitis in Zagreb and Zagreb county, but data from our Hospital did not confirm our hypothesis. In the period from 1999-2001, a total of twenty-seven (27) children with Hib meningitis were treated (average 9 patients per year), so the incidence practically remained the same as in the 11-years period before. However, with the introduction of routine, obligatory Hib vaccination for children in our country, we expect a significant decrease of incidence of Hib meningitis in Zagreb and Croatia. We think that expected decrease in Hib meningitis incidence will occur in the next few years, which correllates with the results from the countries that introduced routine Hib vaccination earlier.

Procjena vrijednosti imunofenotipizacije periferne krvi u dijagnostici sindroma mononukleoze.