The transjugular intrahepatic portosystemic shunt (TIPS) is an important treatment for complications of portal hypertension. As some authors have suggested that TIPS may facilitate liver ...transplantation technically, the objective of this study was to determine the impact of TIPS on the liver transplant operation and its outcome. The analysis was designed as a retrospective cohort study using a multicenter database. Fifty-five patients with TIPS were matched with 55 controls on the basis of 10 pretransplant laboratory, clinical, and demographic features. TIPS patients and control patients were compared with regard to duration of surgery, intraoperative blood product usage, liver and renal function, volume of ascites, survival, and hospital stay. For confirmatory purposes, a parallel analysis using linear regression methods was performed. By matched analysis, TIPS patients had less ascites at surgery (mean 0.9 plus or minus 0.20 vs. 2.2 plus or minus 0.37 L, P=0.005) and a slightly shorter time from incision to cross-clamp (mean 2.1 plus or minus 0.10 vs. 2.5 plus or minus 0.15 hr, P=0.03). However, there were not significant differences for total operative time (mean 6.0 plus or minus 0.17 vs. 6.3 plus or minus 0.25 hr, P=1.00), blood product usage, or any other outcome variable. Regression analysis confirmed these results. TIPS does not significantly impact the course of liver transplantation surgery. Therefore, preoperative portal decompression solely to facilitate liver transplantation is not an appropriate indication for TIPS.
The link between the human sympathoadrenalmedullary system and the adipocyte hormone leptin is controversial. We measured total and regional norepinephrine spillover, epinephrine secretion rate, and ...extra-adipocyte leptin release in 22 lean body mass index (BMI) <26 and 20 obese (BMI >28) normotensive men who underwent arterial and central venous catheterization. Because plasma clearance of leptin is primarily by renal removal, for men at steady state we could estimate whole body leptin release to plasma from renal plasma leptin extraction. Whole body leptin release was 1,950 +/- 643 (means +/- SE) ng/min in obese men and 382 +/- 124 ng/min in lean men (P < 0.05). Total and renal norepinephrine spillover rates correlated directly with whole body leptin secretion rate. Leptin is released from multiple nonadipocyte sites, which we tested by use of simultaneous arteriovenous blood sampling. We found a surprisingly large contribution of brain leptin release to the plasma leptin pool, 529 +/- 175 ng/min (>40% whole body leptin release), with greater leptin release in obese than in lean men, 935 +/- 321 vs. 160 +/- 59 ng/min (P = 0.045). In parallel with leptin measurements, we also quantified brain serotonin turnover and jugular overflow of neuropeptide Y (NPY). Brain serotonin turnover was higher in obese than in lean men, 227 +/- 112 vs. 21 +/- 14 ng/min (P = 0.019), as was overflow of NPY from the brain, 12.9 +/- 1.4 vs. 5.3 +/- 2.2 ng/min (P = 0.042). These results suggest that leptin is released within the brain and at an increased rate in obese humans, in whom activation of brain serotonergic and NPY mechanisms also exists. PUBLICATION ABSTRACT
Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a ...panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated.
Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain serotonin turnover most likely derived not from impaired serotonin reuptake, but from increased firing in serotonergic midbrain raphe neurons projecting to both subcortical brain regions and the cerebral cortex.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
CONTEXT The biological basis for the development of major depressive disorder (MDD) remains incompletely understood. OBJECTIVE To quantify brain serotonin (5-hydroxytryptamine 5-HT) turnover in ...patients with MDD. DESIGN Patients with depression were studied both untreated and during administration of a selective serotonin reuptake inhibitor (SSRI)
in an unblinded study of sequential design. Healthy volunteers were examined on only 1 occasion. Direct internal jugular venous blood sampling was used to directly quantify brain serotonin turnover. The effect of serotonin transporter (5-HTT) genotype on brain serotonin turnover was evaluated and the influence of SSRI therapy on serotonin turnover was investigated. SETTING Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the research catheterization laboratory of a major training hospital and medical research institute. PARTICIPANTS Studies were performed in 21 patients fulfilling the DSM-IV and International Statistical Classification of Diseases, 10th Revision diagnostic criteria for MDD and in 40 healthy volunteers. INTERVENTIONS Treatment for patients consisted of SSRI administration for approximately 12 weeks. MAIN OUTCOME MEASURES Brain serotonin turnover before and after SSRI therapy. RESULTS Brain serotonin turnover was significantly elevated in unmedicated patients with MDD compared with healthy subjects (mean SD internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 4.4 4.3 vs 1.6 2.4 nmol/L, respectively; P = .003). Analysis of the influence of the 5-HTT genotype in MDD indicated that carriage of the s allele compared with the l allele was associated with greater than a 2-fold increase in brain serotonin turnover (mean SD internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.5 4.7 vs 2.7 2.9 nmol/L,
respectively; P = .04). Following SSRI therapy, brain serotonin turnover was substantially reduced (mean SD internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.0 4.0 nmol/L prior to treatment vs 2.0
3.3 nmol/L following therapy; P = .008). CONCLUSIONS Brain serotonin turnover is elevated in unmedicated patients with MDD and is influenced by the 5-HTT genotype. The marked reduction in serotonin turnover following SSRI treatment and the accompanying improvement in symptoms suggest that high brain serotonin turnover may be a biological substrate of MDD.Arch Gen Psychiatry. 2008;65(1):38-46-->
The biological basis for the development of major depressive disorder (MDD) remains incompletely understood. To quantify brain serotonin (5-hydroxytryptamine 5-HT) turnover in patients with MDD. ...Patients with depression were studied both untreated and during administration of a selective serotonin reuptake inhibitor (SSRI) in an unblinded study of sequential design. Healthy volunteers were examined on only 1 occasion. Direct internal jugular venous blood sampling was used to directly quantify brain serotonin turnover. The effect of serotonin transporter (5-HTT) genotype on brain serotonin turnover was evaluated and the influence of SSRI therapy on serotonin turnover was investigated. Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the research catheterization laboratory of a major training hospital and medical research institute. Studies were performed in 21 patients fulfilling the DSM-IV and International Statistical Classification of Diseases, 10th Revision diagnostic criteria for MDD and in 40 healthy volunteers. Treatment for patients consisted of SSRI administration for approximately 12 weeks. Brain serotonin turnover before and after SSRI therapy. Brain serotonin turnover was significantly elevated in unmedicated patients with MDD compared with healthy subjects (mean SD internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 4.4 4.3 vs 1.6 2.4 nmol/L, respectively; P = .003). Analysis of the influence of the 5-HTT genotype in MDD indicated that carriage of the s allele compared with the I allele was associated with greater than a 2-fold increase in brain serotonin turnover (mean SD internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.5 4.7 vs 2.7 2.9 nmol/L, respectively; P = .04). Following SSRI therapy, brain serotonin turnover was substantially reduced (mean SD internal jugular venoarterial 5-hydroxyindoleacetic acid plasma concentration difference, 6.0 4.0 nmol/L prior to treatment vs 2.0 3.3 nmol/L following therapy; P = .008). Brain serotonin turnover is elevated in unmedicated patients with MDD and is influenced by the 5-HTT genotype. The marked reduction in serotonin turnover following SSRI treatment and the accompanying improvement in symptoms suggest that high brain serotonin turnover may be a biological substrate of MDD.