Lažno pozitivni nalaz metadona u mokraći bolesnika liječenog kvetiapinom

We present a case of T.M. admitted to University Department of Psychiatry, Split University Hospital Center, in Croatia, because of the acute psychotic reaction (F23.9). The patient’s urine tested positive for methadone without a history of methadone ingestion. Urine drug screen was performed with the COBAS Integra Methadone II test kit (kinetic interaction of microparticles in solution /KIMS/ methodology) by Roche. Drugs that have been shown to cross-react with methadone feature a tricyclic structure with a sulfur and nitrogen atom in the middle ring, which is common for both quetiapine and methadone. Therefore, it is plausible that this structural similarity between quetiapine and methadone could underlie the cross-reactivity on methadone drug screen. Besides quetiapine, a number of routinely prescribed medications have been associated with triggering false-positive urine drug screen results. Verification of the test results with a different screening test or additional analytical tests should be performed to avoid adverse consequences for the patients.Testovi probira mokraće široko su prihvaćena metoda brzog otkrivanja moguće zloporabe psihoaktivnih supstanca. Najčešće korišteni testovi analize mokraće na droge su imunokemijske metode, unatoč činjenici da su prijavljeni brojni slučajevi lažno-pozitivnih rezultata za mnoge od testova za brzo otkrivanje. Potvrda mogućih pozitivnih probira mokraće na lijekove, koja je neophodna kako bi se smanjio broj prijava lažno pozitivnih rezultata, može biti skupa i zahtijevati veći utrošak vremena za analizu. Prikazuje se slučaj bolesnika T.M. zaprimljenog u Kliniku za psihijatriju Kliničkog bolničkog centra Split poradi akutne psihotične reakcije (F23). U mokraći bolesnika testiranog na metadon isti je otkriven, ali bez potvrde konzumacije istog. Analiza mokraće provedena je testom COBAS Integra Methadone II (kinetička interakcija mikročestica u otopini, metoda KIMS) tvrtke Roche. Lijekovi koji su pokazali križnu reaktivnost s metadonom sadrže tricikličnu strukturu s atomima sumpora i dušika u srednjem prstenu, što je zajedničko i kvetiapinu i metadonu. Stoga je za pretpostaviti da je strukturna sličnost kvetiapina i metadona uzrokom križne reaktivnosti u testu probira na metadon. Uz kvetiapin, velik broj rutinski propisivanih lijekova pokazao je povezanost s pojavom lažno-pozitivnih rezultata u testovima mokraće. Kako bi se izbjegle neželjene posljedice za bolesnike potrebna je verifikacija rezultata dodatnim metodama potvrde

Effect of involuntary respiratory muscle contractions on cerebral oxygenation during apnea in breath-hold divers

Relativno veliki postotak vrhunskih ronilaca na dah tijekom svoje karijere (na treningu ili natjecanju) izgubi svijest. To je skoro isključivo uzrokovano ekstremnom hipoksijom. Budući da je natjecateljsko ronjenje na dah povezano s dubokom moždanom hipoksijom, a u nekim slučajevima i moždanom hipoperfuzijom, vrlo je važno istražiti fiziološke mehanizme kojima se zaštićuje mozak u okolnostima iznimne hipoksije i hiperkapnije koje se javljaju pri ovakvim iznimno dugim apnejama. Maksimalna voljna apneja se sastoji od dvije faze; prva, „mirna faza“ (engl. easy-going phase), traje do tzv. fiziološke točke prijeloma, u kojoj je PpCO2 u arterijskoj krvi dosegnuo razinu na kojoj počinje, zbog stimulacije kemoreceptora, podraživati centar za disanje, i druga, „borbena faza“ (engl. struggle phase), tijekom koje osoba osjeća rastući poriv za udahom i iskazuje nevoljne kontrakcije dišnih mišića (IBM). Nedavno je dokazano da IBM doprinose oporavljanju hemodinamike. Međutim, još se ne zna utječu li IBM i na moždanu oksigenaciju, odnosno, moždani krvni volumen, tj. imaju li zaštitno djelovanje na funkciju neurona, čime bi se uvrstili u čimbenike koji dovode do produljenja trajanja apneje. Cilj ove doktorske disertacije jest testirati hipotezu da IBM, zajedno sa simpatički posredovanom perifernom vazokonstrikcijom i napredujućom hiperkapničkom moždanom vazodilatacijom, doprinose poboljšanju moždane oksigenacije, čime ju se uspijeva, i tijekom dugih apneja, održati na zadovoljavajućoj razini. Dodatni je cilj proučiti i kvantificirati IBM svojstva (trajanje, amplitudu i prosječnu frekvenciju izbijanja) u raznim dijelovima druge faze (borbene faze) maksimalne voljne apneje u suhim uvjetima. U tu svrhu, ispitivali smo promjene centralne hemodinamike, zasićenost arterijske krvi kisikom, promjene regionalnoga moždanog i mišićnog oksihemoglobina, deoksihemoglobina i ukupnoga hemoglobina, te svojstva IBM-a tijekom maksimalne voljne apneje u suhim uvjetima u jedanaest (11) vrhunskih ronilaca na dah. Rezultati su pokazali da se, u usporedbi s početnim dijelom borbene faze, prosječna frekvencija izbijanja IBM-a povećala (približno 100%), a trajanje pojedinog IBM-a smanjilo (~ 30%), dok se amplituda nije značajno mijenjala. U svih je ispitanika bio vidljiv stalan porast moždanoga deoksihemoglobina (bdHb) i moždanoga ukupnog hemoglobina (bTHb) tijekom cijele borbene faze, dok se vrijednost moždanoga oksihemoglobina (bO2Hb) mijenjala dvojako; rasla je od početka do sredine borbene faze, te postupno padala pri kraju apneje. Tijekom borbene faze, srednji arterijski tlak (MAP) je rastao iako se ukupni periferni otpor nije povećavao, što upućuje na to da se nije mijenjala periferna vazokonstrikcija i podrazumijeva da su IBM pozitivno utjecali na oporavak srčanoga minutnog volumena (primarno, oporavljanjem srčanoga udarnog volumena). Kratke i iznenadne poraste MAP-a, potaknute IBM-om, su pratila slična kolebanja bO2Hb. Ovi rezultati upućuju na zaključak da su porast moždanoga krvnog volumena, a time i moždane oksigenacije, tijekom borbene faze apneje u suhim uvjetima, najvjerojatnije uzrokovali IBM, te periferna vazokonstrikcija i hiperkapnijom potaknuta moždana vazodilatacija.Relatively large percentage of elite breath-hold divers experience loss of consciousness (during training or competition) troughout their career. The loss of consciousness is almost always a result of extreme hypoxia. Since competitive free-diving is associated with profound hypoxia of the brain tissue, and in some cases with cerebral hypoperfusion, it is very important to investigate physiological mechanisms which protect brain in these conditions which are found in extremely long breath-holds. Maximal voluntary apnea is divided into two phases; the initial or easy-going phase, that lasts until the physiological breaking point, when the accumulated carbon dioxide (CO2) stimulates the respiratory drive, and the struggle phase, during which the subject feels a growing urge to breathe and shows progressive involuntary breathing movements (IBM). Recently it was shown that IBM are involved in restoration of hemodynamics. However, it is still unknown wheter the IBM influence the cerebral oxygenation, i. e. do they have a protective effect on neuronal function, which would incorporate them in group of factors that are helping to prolong the maximal apneic time. The aim of this doctoral dissertation is to test the hypotesis that IBM, together with peripheral vasoconstriction and progressive hypercapnia, have a beneficial influence on the brain oxygenation, and therefore may help to maintain it, even during long breath-holds. An additional aim is to study and to quantify the IBM characteristics (duration, amplitude and average frequency) during different parts of the struggle phase of maximal voluntary breath-hold in dry conditions. The central hemodynamics, arterial oxygen saturation, muscular and brain regional oxyhemoglobin, deoxyhemoglobin and total hemoglobin changes and IBM characteristics were monitored during maximal breath-hold in dry conditions in eleven (11) elite divers. The results showed that, compared to the beginning of the struggle phase, the average frequency of IBM increased (by approximately 100%) and their duration decreased (~ 30%) towards the end of the struggle phase, whereas the amplitude was unchanged. In all subjects a consistent increase in brain deoxyhemoglobin (bdHb) and brain total hemoglobin (bTHb) was also found during whole struggle phase, whereas brain oxyhemoglobin (bO2Hb) changed biphasically; it initially increased until the middle of the struggle phase, with the subsequent relative decline at the end of the breath-hold. Mean arterial pressure (MAP) was elevated during the struggle phase although there was no further rise in the peripheral resistance, suggesting unchanged peripheral vasoconstriction and implying the beneficial influence of the IBM on the cardiac output recovery (primarily by restoration of the stroke volume). The IBM induced short lasting sudden increases in MAP were followed by similar oscillations in bO2Hb. These results suggest that an increase in the cerebral blood volume and therefore in the brain oxygenation, observed during the struggle phase of maximal voluntary apnea in dry conditions, is most likely caused by the IBM at the time of the hypercapnia-induced cerebral vasodilatation and peripheral vasoconstriction

Effect of involuntary respiratory muscle contractions on cerebral oxygenation during apnea in breath-hold divers

Relativno veliki postotak vrhunskih ronilaca na dah tijekom svoje karijere (na treningu ili natjecanju) izgubi svijest. To je skoro isključivo uzrokovano ekstremnom hipoksijom. Budući da je natjecateljsko ronjenje na dah povezano s dubokom moždanom hipoksijom, a u nekim slučajevima i moždanom hipoperfuzijom, vrlo je važno istražiti fiziološke mehanizme kojima se zaštićuje mozak u okolnostima iznimne hipoksije i hiperkapnije koje se javljaju pri ovakvim iznimno dugim apnejama. Maksimalna voljna apneja se sastoji od dvije faze; prva, „mirna faza“ (engl. easy-going phase), traje do tzv. fiziološke točke prijeloma, u kojoj je PpCO2 u arterijskoj krvi dosegnuo razinu na kojoj počinje, zbog stimulacije kemoreceptora, podraživati centar za disanje, i druga, „borbena faza“ (engl. struggle phase), tijekom koje osoba osjeća rastući poriv za udahom i iskazuje nevoljne kontrakcije dišnih mišića (IBM). Nedavno je dokazano da IBM doprinose oporavljanju hemodinamike. Međutim, još se ne zna utječu li IBM i na moždanu oksigenaciju, odnosno, moždani krvni volumen, tj. imaju li zaštitno djelovanje na funkciju neurona, čime bi se uvrstili u čimbenike koji dovode do produljenja trajanja apneje. Cilj ove doktorske disertacije jest testirati hipotezu da IBM, zajedno sa simpatički posredovanom perifernom vazokonstrikcijom i napredujućom hiperkapničkom moždanom vazodilatacijom, doprinose poboljšanju moždane oksigenacije, čime ju se uspijeva, i tijekom dugih apneja, održati na zadovoljavajućoj razini. Dodatni je cilj proučiti i kvantificirati IBM svojstva (trajanje, amplitudu i prosječnu frekvenciju izbijanja) u raznim dijelovima druge faze (borbene faze) maksimalne voljne apneje u suhim uvjetima. U tu svrhu, ispitivali smo promjene centralne hemodinamike, zasićenost arterijske krvi kisikom, promjene regionalnoga moždanog i mišićnog oksihemoglobina, deoksihemoglobina i ukupnoga hemoglobina, te svojstva IBM-a tijekom maksimalne voljne apneje u suhim uvjetima u jedanaest (11) vrhunskih ronilaca na dah. Rezultati su pokazali da se, u usporedbi s početnim dijelom borbene faze, prosječna frekvencija izbijanja IBM-a povećala (približno 100%), a trajanje pojedinog IBM-a smanjilo (~ 30%), dok se amplituda nije značajno mijenjala. U svih je ispitanika bio vidljiv stalan porast moždanoga deoksihemoglobina (bdHb) i moždanoga ukupnog hemoglobina (bTHb) tijekom cijele borbene faze, dok se vrijednost moždanoga oksihemoglobina (bO2Hb) mijenjala dvojako; rasla je od početka do sredine borbene faze, te postupno padala pri kraju apneje. Tijekom borbene faze, srednji arterijski tlak (MAP) je rastao iako se ukupni periferni otpor nije povećavao, što upućuje na to da se nije mijenjala periferna vazokonstrikcija i podrazumijeva da su IBM pozitivno utjecali na oporavak srčanoga minutnog volumena (primarno, oporavljanjem srčanoga udarnog volumena). Kratke i iznenadne poraste MAP-a, potaknute IBM-om, su pratila slična kolebanja bO2Hb. Ovi rezultati upućuju na zaključak da su porast moždanoga krvnog volumena, a time i moždane oksigenacije, tijekom borbene faze apneje u suhim uvjetima, najvjerojatnije uzrokovali IBM, te periferna vazokonstrikcija i hiperkapnijom potaknuta moždana vazodilatacija.Relatively large percentage of elite breath-hold divers experience loss of consciousness (during training or competition) troughout their career. The loss of consciousness is almost always a result of extreme hypoxia. Since competitive free-diving is associated with profound hypoxia of the brain tissue, and in some cases with cerebral hypoperfusion, it is very important to investigate physiological mechanisms which protect brain in these conditions which are found in extremely long breath-holds. Maximal voluntary apnea is divided into two phases; the initial or easy-going phase, that lasts until the physiological breaking point, when the accumulated carbon dioxide (CO2) stimulates the respiratory drive, and the struggle phase, during which the subject feels a growing urge to breathe and shows progressive involuntary breathing movements (IBM). Recently it was shown that IBM are involved in restoration of hemodynamics. However, it is still unknown wheter the IBM influence the cerebral oxygenation, i. e. do they have a protective effect on neuronal function, which would incorporate them in group of factors that are helping to prolong the maximal apneic time. The aim of this doctoral dissertation is to test the hypotesis that IBM, together with peripheral vasoconstriction and progressive hypercapnia, have a beneficial influence on the brain oxygenation, and therefore may help to maintain it, even during long breath-holds. An additional aim is to study and to quantify the IBM characteristics (duration, amplitude and average frequency) during different parts of the struggle phase of maximal voluntary breath-hold in dry conditions. The central hemodynamics, arterial oxygen saturation, muscular and brain regional oxyhemoglobin, deoxyhemoglobin and total hemoglobin changes and IBM characteristics were monitored during maximal breath-hold in dry conditions in eleven (11) elite divers. The results showed that, compared to the beginning of the struggle phase, the average frequency of IBM increased (by approximately 100%) and their duration decreased (~ 30%) towards the end of the struggle phase, whereas the amplitude was unchanged. In all subjects a consistent increase in brain deoxyhemoglobin (bdHb) and brain total hemoglobin (bTHb) was also found during whole struggle phase, whereas brain oxyhemoglobin (bO2Hb) changed biphasically; it initially increased until the middle of the struggle phase, with the subsequent relative decline at the end of the breath-hold. Mean arterial pressure (MAP) was elevated during the struggle phase although there was no further rise in the peripheral resistance, suggesting unchanged peripheral vasoconstriction and implying the beneficial influence of the IBM on the cardiac output recovery (primarily by restoration of the stroke volume). The IBM induced short lasting sudden increases in MAP were followed by similar oscillations in bO2Hb. These results suggest that an increase in the cerebral blood volume and therefore in the brain oxygenation, observed during the struggle phase of maximal voluntary apnea in dry conditions, is most likely caused by the IBM at the time of the hypercapnia-induced cerebral vasodilatation and peripheral vasoconstriction