31 Objectives Previous studies on addiction suggest disturbances in the dopamine transmission system. This [18F]FDOPA-PET investigation aims to detect nicotine related changes during continued smoking, after acute withdrawal, and after long-term abstinence. The latter condition should simulate the situation before the substance-dependent behaviour became apparent. The reversible inlet/outlet model for [18F]FDOPA-PET analysis was applied for characterization of divers presynaptic kinetic parameters. Methods 30 male nicotine dependent subjects (28.3±7.0 yrs) and 15 non-smoking subjects (27.9±7.5 yrs) were included. Half of the patients underwent a first scan under acute withdrawal the other half under smoking conditions. Afterwards, all patients attended at a smoking cessation program. 16/30 patients remained abstinent for at least 3 months. This group underwent a second [18F]FDOPA scan (124 min., bolus infusion 228±32 MBq [patients]; arterial blood withdrawal; metabolite detection). The reversible inlet/outlet model of Kumakura et al. (2005) was applied in order to obtain the net blood/brain clearance (K), the loss of fluorinated metabolites (kloss), and the total distribution volume (VD). Results Positive correlations between the dopamine transmission and cognitive performance could be replicated (TMT-B vs. VD in vNC: r=-0.631, p=0.016). Smoking patients showed a reduced dopamine synthesis capacity in particular in the right (-16%, p=0.045) and left ventral caudate nucleus (-16%, p=0.050). The kloss sowed a reduction on trend-level. The long-term smoking cessation, nevertheless, normalized all presynaptic dopaminergic parameters. The state of acute withdrawal showed a tendency toward reduced K and kloss. Conclusions Ongoing nicotine consumption results in a down-regulation of dopamine-synthesis capacity and turn-over. The complete normalization after 3 months of abstinence, however, was unexpected and does not claim an inefficient dopamine system to be a strong trait toward nicotine dependence.
We describe the experience from a single institution with the Norwood sequence of palliation for hypoplasia of the left heart, emphasizing complications related to placement of a conduit from the right ventricle to the pulmonary arteries and their management.Between November, 2002 and January, 2006, we palliated 32 patients with hypoplastic left heart syndrome or its variants by placing a conduit from the right ventricle to the pulmonary arteries. We reviewed retrospectively the charts and angiograms from these patients.Hospital survival after construction of the conduit was 90.6%. There were 3 interstage deaths, of which 2 were likely due severe obstruction of the conduit. Stents were implanted into the proximal or medial portions of the conduits of 3 patients. Early revision of the distal anastomosis, and shortening the conduit, was performed early postoperatively in 2 patients. So far, 24 out 26 survivors of the first stage underwent a bi-directional cavopulmonary anastomosis after a mean interval of 4.3 plus or minus 1.4 months. Of these, 3 required a semi-urgent second stage of palliation because of worsening cyanosis, with one patient dying after the second stage. Completion of the Fontan circulation by insertion of an extracardiac conduit was performed in 8 patients at the mean age of 19.8 plus or minus 2.2 months. We were able to achieve biventricular repair in 1 patient, with aortic atresia, hypoplastic arch and ventricular septal defect, 4.3 months after the initial palliative procedure. Overall survival of the whole cohort of 32 patients was 78.9%, plus or minus 7.8%, at 5 months, and 74.3%, plus or minus 8.6%, up to 25 months.The introduction of the conduit placed from the right ventricle to the pulmonary arteries has led to an improved outcome in the complex entity of hypoplastic left heart syndrome and its variants. Stenosis of the conduit, nonetheless, may account for significant interstage morbidity, and often requires intervention or early installation of the second stage of palliation.
Methylphenidate (MPH) inhibits the reuptake of dopamine and noradrenaline. PET studies with MPH challenge show increased competition at postsynaptic D 2/3 -receptors, thus indirectly revealing presynaptic dopamine release. We used [ 18 F]fluorodopamine ([ 18 F]FDOPA)-PET in conjunction with the inlet–outlet model (IOM) of Kumakura et al. (2007) to investigate acute and long-term changes in dopamine synthesis capacity and turnover in nigrostriatal fibers of healthy subjects with MPH challenge. Twenty healthy human females underwent two dynamic [ 18 F]FDOPA PET scans (124 min; slow bolus-injection; arterial blood sampling), with one scan in untreated baseline condition and the other after MPH administration (0.5 mg/kg, p.o.), in randomized order. Subjects underwent cognitive testing at each PET session. Time activity curves were obtained for ventral putamen and caudate and were analyzed according to the IOM to obtain the regional net-uptake of [ 18 F]FDOPA ( K ; dopamine synthesis capacity) as well as the [ 18 F]fluorodopamine washout rate ( k loss , index of dopamine turnover). MPH substantially decreased k loss in putamen (−22%; p = 0.003). In the reversed treatment order group (MPH/no drug), K was increased by 18% at no drug follow-up. The magnitude of K at the no drug baseline correlated with cognitive parameters. Furthermore, individual k loss changes correlated with altered cognitive performance under MPH. [ 18 F]FDOPA PET in combination with the IOM detects an MPH-evoked decrease in striatal dopamine turnover, in accordance with the known acute pharmacodynamics of MPH. Furthermore, the scan-ordering effect on K suggested that a single MPH challenge persistently increased striatal dopamine synthesis capacity. Attenuation of dopamine turnover by MPH is linked to enhanced cognitive performance in healthy females.
