Test-retest reproducibility of extrastriatal dopamine D2 receptor imaging with [123I]epidepride SPECT in humans.

This study evaluated the test-retest reproducibility of D2 receptor quantification in the thalamus and temporal cortex using [123I]epidepride SPECT. METHODS: Ten healthy volunteers (4 men, 6 women; age range, 19-46 y) underwent 2 SPECT studies (interval, 2-26 d) using a bolus-plus-constant-infusion paradigm (bolus-to-infusion ratio = 6 h; infusion time = 9 h). Plasma clearance (in liters per hour) and free fraction (f1) of the parent tracer were measured. Radioactivity (in becquerels per gram) in the thalamus, temporal cortex, and cerebellum were normalized to the infusion rate (in becquerels per hour). Normalized striatal radioactivity was also measured to assess reproducibility in regions with a high density of receptors and better counting statistics. The outcome measures obtained were V3 (receptor density [Bmax]/equilibrium dissociation constant [KD]), V3' (f1 x Bmax/KD), and RT (specific-to-nondisplaceable tissue ratio). RESULTS: Test-retest variability and reliability (intraclass correlation coefficient) were 10.8% and 0.88, respectively, for plasma clearance and 15.3% and 0.77, respectively, for f1. The test-retest variability of brain-specific (target minus nondisplaceable) radioactivity was higher in the thalamus and temporal cortex than in the striatum, although reliability was comparable. Among the outcome measures, V3' showed better test-retest variability and reliability in the thalamus (13.3% and 0.75, respectively) and temporal cortex (13.4% and 0.86, respectively). CONCLUSION: Brain radioactivity was the main source of variability for quantification of extrastriatal D2 receptors with [123I]epidepride. The reproducibility of outcome measures in extrastriatal regions was good. However, because receptor density was lower in extrastriatal regions than in the striatum, the counting statistics in these regions were low and reproducibility was affected by the higher test-retest variability of brain-specific radioactivity. Compared with V3 and V3', RT showed less test-retest variability in the thalamus and temporal cortex but lower reliability. Moreover, measurement of RT may be affected by the presence of potential lipophilic metabolites entering the brain.     

Plasticity of inhibitory synaptic network interactions in the lateral amygdala upon fear conditioning in mice

After fear conditioning, plastic changes of excitatory synaptic transmission occur in the amygdala. Fear‐related memory also involves the GABAergic system, although no influence on inhibitory synaptic transmission is known. In the present study we assessed the influence of Pavlovian fear conditioning on the plasticity of GABAergic synaptic interactions in the lateral amygdala (LA) in brain slices prepared from fear‐conditioned, pseudo‐trained and naïve adult mice. Theta‐burst tetanization of thalamic afferent inputs to the LA evoked an input‐specific potentiation of inhibitory postsynaptic responses in projection neurons; the cortical input was unaffected. Philanthotoxin (10 µm ), an antagonist of Ca²⁺‐permeable AMPA receptors, disabled this plastic phenomenon. Surgical isolation of the LA, extracellular application of a GABA_B receptor antagonist (CGP 55845A, 10 µm ) or an NMDA receptor antagonist (APV, 50 µm ), or intracellular application of BAPTA (10 mm ), did not influence the plasticity. The plasticity also showed as a potentiation of monosynaptic excitatory responses in putative GABAergic interneurons. Pavlovian fear conditioning, but not pseudo‐conditioning, resulted in a significant reduction in this potentiation that was evident 24 h after training. Two weeks after training, the potentiation returned to control levels. In conclusion, a reduction in potentiation of inhibitory synaptic interactions occurs in the LA and may contribute to a shift in synaptic balance towards excitatory signal flow during the processes of fear‐memory acquisition or consolidation.     

Theta resynchronization during reconsolidation of remote contextual fear memory

We have recently demonstrated high theta-phase synchronization between the lateral amygdala and CA1 area of the hippocampus during retrieval of long-term (1 day) fear memory, and not during short-term (2 h) or remote memory retrieval (30 days). These results indicated that the amygdalo-hippocampal interaction reflects a dynamic change of ensemble activities related to various stages of fear memory storage. In this study, we investigated theta activity during the reconsolidation of a remote contextual fear memory by re-exposing animals to the shock context 30 days after training. Consistent with our previous results, high theta synchronization was no longer apparent during re-exposure to the shock context, but was significantly higher 1 day after context re-exposure. These data indicate that the reconsolidation of remote contextual fear memory includes changes in ensemble activities between the lateral amygdala and CA1.     

Detection of hypoventilation during thoracoscopy: combined cutaneous carbon dioxide tension and oximetry monitoring with a new digital sensor

BACKGROUND: Changes in Paco(2) have not been described during thoracoscopy under sedation-assisted local anesthesia. We hypothesized that hypoventilation might occur secondary to administration of sedatives and decreased ventilation in one lung.Aim: Prospectively measure cutaneous carbon dioxide tension (Pcco(2)) in addition to pulse oximetric saturation (Spo(2)) using a new combined digital sensor to examine the occurrence of hypoventilation during thoracoscopy under sedation-assisted local anesthesia. SETTING: University hospital. METHODS: Following validation studies, Pcco(2) was prospectively measured in 16 consecutive patients undergoing thoracoscopy under sedation-assisted local anesthesia using a combined digital earlobe sensor measuring Spo(2) (percentage) and Pcco(2) (millimeters of mercury). All patients received supplemental oxygen. Routine BP monitoring and Spo(2) was continued. Patients received IV hydrocodone, 5 mg, and intermittent boluses or IV midazolam and pethidine. RESULTS: Mean baseline Pcco(2) measurement was 39.1 +/- 7.2 mm Hg (+/- SD) [range, 27.5 to 50.5 mm Hg], and peak measurement during the procedure was 52.3 +/- 10.3 mm Hg (range, 37.2 to 77 mm Hg) [p < 0.001]. Median and mean changes in Pcco(2) measurement from baseline were 13.0 mm Hg and 13.2 +/- 5.3 mm Hg (range, 5.5 to 27.8 mm Hg), respectively. Mean fall in Spo(2) during the procedure was 4.6 +/- 3.2% (range, 1 to 14%). CONCLUSIONS: Thoracoscopy performed under sedation-assisted local anesthesia is associated with significant hypoventilation. Combined measurement of Spo(2) and Pcco(2) during thoracoscopy is a novel approach in the monitoring of ventilation, enhancing patient safety, and might allow to guide the administration of sedation in a better way.     

Effect of garlic (Allium sativum) oil on exercise tolerance in patients with coronary artery disease

The effect of six weeks garlic oil administration was observed on cardiac performance and exercise tolerance in 30 patients of coronary artery disease. After initial treadmill stress test, they were administered garlic oil in the dose of four capsules twice a day for 6 weeks and treadmill stress test was repeated. Garlic significantly (P<0.01) reduced heart rate at peak exercise and also significantly reduced the work load upon the heart resulting in better exercise tolerance (P<0.05) as compared to the initial test. It appears to be a good adaptogen to be utilized in patients with coronary artery disease.     

123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia

Deficient inhibitory neurotransmission of gamma-aminobutyric acid (GABA) has been implicated in the pathophysiology of schizophrenia based on postmortem studies. However, in vivo studies have shown predominantly negative or conflicting results. The goal of this study was to better characterize possible changes of the regional GABA(A)-benzodiazepine receptor distribution volume (BZR V3-p) in schizophrenia in vivo, using a larger sample size than previous studies. Single photon emission computed tomography (SPECT) with [123I]iomazenil was used with a constant infusion paradigm to measure the BZR V3-p under sustained radiotracer equilibrium conditions. Twenty-five patients with schizophrenia and 24 matched healthy control subjects were studied. Positive and Negative Syndrome Scale (PANSS) ratings were done in all subjects. Statistical parametric mapping (SPM) 96 was used to compare patients and control subjects as well as to study the relationship between SPECT results and composite PANSS scores based on two factorial models: the pentagonal model (positive, negative, dysphoric mood, activation, and autistic preoccupation factors) and the taxometric model (disorganized dimension). On the basis of 'absolute' values of V3-p with no normalization for total brain uptake, the schizophrenic patients showed no significant differences in BZR levels compared to the healthy control subjects. With a global normalization procedure, which is more sensitive to relative regional differences in activity, BZR V3-p was significantly decreased in the patients in the left precentral gyrus (BA 6). The relative BZR V3-p showed a significant positive correlation with duration of illness in the superior occipital gyri (BA 19). No significant correlations were observed between either absolute or relative BZR V3-p and either age or any of the composite PANSS scores based on any of the two factorial models in either patients or control subjects. No significant differences were observed between cigarette smoking vs. non-smoking patients, nor between the patients on atypical antipsychotics vs. on typical antipsychotics vs. not on any antipsychotics. In general, no significant differences in BZR V3-p were observed between patients and control subjects, except for a decrease in relative BZR V3-p in the left precentral gyrus. Grey matter atrophy is unlikely to be the cause for this decrease. However, we could not exclude that possibility. The positive correlation with duration of illness might reflect the relative preservation of neurons expressing BZR in the superior occipital gyri as compared to other cortical brain regions in schizophrenia.