Platelet-poor Plasma Serotonin Research Articles

Plasma Serotonin and Cardiovascular Outcomes in Chronic Kidney Disease.

Background Platelet-poor plasma serotonin levels are associated with adverse cardiovascular outcomes. Although plasma serotonin levels increase in chronic kidney disease, the cardiovascular implications remain unknown. Methods and Results In 1114 participants from the prospective CRIC (Chronic Renal Insufficiency Cohort) Study, we evaluated the association between plasma serotonin, categorized as undetectable, intermediate, and high (≥20 ng/mL) levels, and cross-sectional findings on echocardiography, including left ventricular hypertrophy, left ventricular ejection fraction, and pulmonary hypertension. We also analyzed whether serotonin was associated with time-to-event cardiovascular outcomes, including heart failure hospitalization and atherosclerotic cardiovascular disease (ASCVD) events, in addition to mortality. Because selective serotonin reuptake inhibitors decrease plasma serotonin levels, we specifically evaluated the influence of selective serotonin reuptake inhibitor use in the relationship between serotonin and outcomes. Plasma serotonin level inversely correlated with estimated glomerular filtration rate and directly correlated with blood pressure. High plasma serotonin was associated with left ventricular hypertrophy (adjusted odds ratio, 2.74 [95% CI, 1.11-7.41]). In contrast, undetectable plasma serotonin level was associated with the highest risk of heart failure (adjusted hazard ratio [HR], 2.26 [95% CI, 1.40-3.66]) and ASCVD events (adjusted HR, 1.96 [95% CI, 1.15-3.32]). Conclusions In a large chronic kidney disease cohort, plasma serotonin levels correlated with blood pressure, and elevated serotonin levels were associated with left ventricular hypertrophy. In contrast, undetectable plasma serotonin was associated with the highest risk of heart failure and ASCVD events.

Comparison of pre-analytical conditions for quantification of serotonin in platelet-poor plasma

BackgroundReported concentrations of serotonin in platelet-poor plasma (PPP) in healthy subjects vary widely due to different pre-analytical procedures. AimTo examine how different pre-analytical conditions affect the measured concentration of serotonin in PPP. MethodSix pre-analytical protocols were compared for preparation of PPP from EDTA whole blood for quantification of serotonin from nine healthy individuals. Three combinations of centrifugation with a mild centrifugation of gel-free EDTA tubes followed by a stronger centrifugation were compared to single-stage centrifugation of EDTA tubes with separator gel and heat shock treatment of blood prior to centrifugation. All samples were analysed using the same enzyme linked immunosorbent assay (ELISA) method. ResultsFindings show that two consecutive centrifugations; first a mild centrifugation at 100 or 200×g followed by centrifugation at 4500 or 14500×g resulted in the lowest serotonin concentration in PPP. ConclusionTwo successive centrifugations to produce PPP for serotonin analysis; first a mild centrifugation to avoid mechanical stress on the platelets, and next a stronger centrifugation to remove platelets, is superior to the use of gel tubes and heat shock treatment.

Abstract 12834: Increased Plasma Serotonin and Circulating microRNA-1914 Reflect Oxidative Stress and Play Crucial Roles in Atherosclerosis

Introduction: Serotonin, synthesized from enterochromaffin cells, modulates vascular tonus and thrombus formation, and mediates development of atherosclerotic plaque. Oxidative stress is involved in vascular inflammation and progression of atherosclerosis. Hypothesis: We hypothesized that plasma serotonin plays a crucial role in increasing oxidative stress and aimed to identify the circulating microRNA(s) associated with serotonin ratio for coronary artery disease (CAD). Methods: Blood was sampled from 120 outpatients with cardiovascular risk factors but without a history of previous cardiovascular events. Serotonin levels both in platelet poor plasma (PPP) and whole blood (WB) were measured with HPLC, and the ratio of serotonin in PPP to that in WB (PPP/WB) was used as an index of platelet activation. For assessment of oxidative stress, serum levels of derivative reactive oxygen metabolites (d-ROM) were measured. Total RNA was isolated from subjects who were scheduled for coronary angiography with suspicion of CAD and a microRNA array analysis was performed. The expression levels of microRNAs were scaled by global normalization. Results: Serotonin levels in both PPP and PPP/WB ratio were significantly correlated with the d-ROM levels. Among enrolled patients, 25 subjects were diagnosed as having CAD. The levels of the PPP/WB ratio of serotonin, d-ROM, and CRP were significantly higher in subjects with CAD than in those without CAD. Logistic regression analysis performed with endpoint of having CAD revealed that the PPP/WB ratio of serotonin was independently associated with CAD. In subjects with CAD, 5 increased microRNAs and 30 decreased microRNAs were identified among more than 2000 microRNAs as compared to those without CAD. Among candidate microRNAs, expression of microRNA-1914 showed significant inverse correlation with PPP/WB ratio (r=-0.61, P<0.05) and d-ROM levels (r=-0.63, P<0.05). Conclusions: A significant association among platelet activation assessed by PPP and PPP/WB ratio and oxidative stress assessed by d-ROM, was detected in individuals with cardiovascular risk factors. Targeting serotonin-oxidative stress axis, and circulating microRNA-1914 may serve as novel strategy for diagnosis of atherosclerotic CAD.

Serotonin in peripheral blood reflects oxidative stress and plays a crucial role in atherosclerosis: Novel insights toward holistic anti-atherothrombotic strategy

We enrolled 132 outpatients with cardiovascular risk factors to evaluate the serotonin levels in platelet-poor plasma (PPP) and whole blood (WB). PPP serotonin levels and PPP/WB serotonin ratio were significantly correlated with levels of oxidative stress measured by derivative reactive oxygen metabolites (d-ROM). Twenty-five subjects were revealed to have stable coronary artery disease (CAD), and the levels CRP, d-ROM, and PPP/WB serotonin ratio were significantly higher in subjects with CAD than in those without CAD. Logistic regression analysis performed with the endpoint of having CAD revealed that the PPP/WB serotonin ratio was independently associated with CAD (odds ratio 3.37, 95% confidence interval 1.04–10.9, P = 0.04). Receiver operating characteristic (ROC) curve analyses to discriminate subjects with CAD from those without CAD indicated that combining PPP/WB serotonin ratio and d-ROM improved diagnostic utility. Targeting the serotonin–oxidative stress axis as part of a holistic anti-atherothrombotic strategy could be beneficial for patients with atherosclerosis.

Measurement of Plasma, Serum, and Platelet Serotonin in Individuals With High Bone Mass and Mutations in LRP5

It has recently been suggested that the low-density lipoprotein receptor-related protein 5 (LRP5) regulates bone mass by suppressing secretion of serotonin from duodenal enterochromaffin cells. In mice with targeted expression of a high bone mass-causing (HBM-causing) LRP5 mutation and in humans with HBM LRP5 mutations, circulating serotonin levels have been reported to be lower than in controls whereas individuals with loss-of-function mutations in LRP5 have high blood serotonin. In contrast, others have reported that conditionally activating a knock-in allele of an HBM-causing LRP5 mutation in several tissues, or genetic deletion of LRP5 in mice has no effect on serum serotonin levels. To further explore the possible association between HBM-causing LRP5 mutations and circulating serotonin, levels of the hormone were measured in the platelet poor plasma (PPP), serum, and platelet pellet (PP) of 16 affected individuals from 2 kindreds with HBM-causing LRP5 mutations (G171V and N198S) and 16 age-matched controls. When analyzed by HPLC, there were no differences in levels of serotonin in PPP and PP between affected individuals and age-matched controls. Similarly, when analyzed by ELISA, there were no differences in PPP or PP between these two groups. By ELISA, serum levels of serotonin were higher in the affected individuals when compared to age-matched controls. A subgroup analysis of only the G171V subjects (n=14) demonstrated that there were no differences in PPP and PP serotonin between affected individuals and controls when analyzed by HPLC. PP serotonin was lower in the affected individuals when measured by ELISA but serum serotonin levels were not different. We conclude that there is no change in PPP serotonin in individuals with HBM-causing mutations in LRP5.

Cigarette smoking induces vascular damage of both conduit arteries and small vessels and persistent elevation of plasma serotonin unresponsive to 8 weeks of smoking cessation

Purpose: Cigarette smoking is one of the major risk factors of cardiovascular diseases and induces deleterious vascular damages. Whereas serotonin released to plasma upon platelet activation modulates vascular tonus and thrombus formation. The purpose of this study was to examine the plasma levels of serotonin in habitual cigarette smokers and the kinetics of plasma serotonin after smoking cessation, and their association with endothelial function. Methods: In study 1, clinical profiles including endothelial function were compared between apparently healthy male smokers (n=27, 40±8 years) and age-adjusted non-smokers (n=21, 40±7 years). In study 2, smokers were instructed to stop smoking and clinical profiles and laboratory findings including serum level of cotinine, principal metabolite of nicotine, were investigated before and after 8 weeks of smoking cessation. Strict precautions were taken to obtain platelet poor plasma (PPP). Serotonin levels in PPP were measured by HPLC. Endothelial function was assessed by 2 distinct techniques, namely flow-mediated dilation (FMD) using ultrasound system for conduit arteries and peripheral arterial tonometry (PAT) using End-PAT 2000 for peripheral small vessels. Results: In Study 1, levels of PPP serotonin and serotonin corrected by platelets number (serotonin/plt) in smokers were higher than those in non-smokers (6.90±2.91 vs 4.60±2.32 nmol/L, P<0.01; and 31.3±16.6 vs 20.6±11.9 x10-9 pmol/plt, P<0.05; respectively), and FMD in smokers was lower than that in non-smokers (3.12±1.15 vs 4.11±1.93%, P<0.05). In study 2, serotonin/plt in PPP (33.5±19.4 x10-9 pmol/plt) correlated positively with serum level of cotinine (152±140 ng/ml, r=0.45, P<0.05) and inversely with HDL cholesterol (61±16 mg/dl, r=-0.46, P<0.05) and PAT ratio (0.25±0.10, r=-0.45, P<0.05). Smokers who completely attained smoking cessation indicated significantly increased PAT ratio (P<0.05) although serotonin and serotonin/plt in PPP were not significantly changed. Conclusions: Cigarette smoking is associated with increase of plasma serotonin and impaired endothelial function in middle-aged healthy subjects. Moreover, the change was unresponsive to 8 weeks of smoking cessation, suggesting that caution should be taken during plasma serotonin levels are not decreased even after improvement of endothelial function.

Serotonin in blood: Assessment of its origin by concomitant determination of β-thromboglobulin (platelets) and chromogranin A (enterochromaffin cells)

Background. Serotonin is produced in enterochromaffin (EC) cells, taken up and stored in platelets and released during platelet activation. Measurement of platelet-poor plasma serotonin is difficult, mainly due to platelet activation during blood sampling. We aimed to establish a method to assess the influence of platelet release upon platelet-poor plasma serotonin measurement by concomitant determination of serotonin, β-thromboglobulin (β-TG) and chromogranin A (CgA). Methods. Blood samples from patients with thrombocytosis, thrombocytopenia and small intestinal neuroendocrine (EC-cell) tumors (SI-NETs) as well as healthy volunteers were analyzed. We also measured serotonin in venous and arterial samples from patients undergoing coronary angiography to evaluate peripheral serotonin metabolism. Results. Serotonin and CgA were significantly higher in patients with SI-NETs compared to all other groups implying EC cell origin of serotonin in patients with SI-NETs. We found that the serotonin concentration was similar in patients with thrombocytosis and thrombocytopenia, whereas plasma β-TG was higher and lower respectively. A high EDTA concentration in the sampling tubes gave significantly lower serotonin concentrations. Serotonin concentrations did not differ between arterial and venous blood. Conclusions. Our methodology to measure platelet-poor plasma serotonin was appropriate. Blood platelet numbers did not affect the level of serotonin in contrast to β-TG.

The Measurement of Platelet-Poor Plasma Serotonin: A Systematic Review of Prior Reports and Recommendations for Improved Analysis

Recent reports of new and important roles for serotonin (5-hydroxytryptamine, 5-HT) in the periphery have substantially increased interest in measuring peripheral serotonin. Nearly all circulating serotonin is found within platelets and this pool has been assessed by measuring serotonin in whole blood or in platelet-rich plasma. Measurement of the much smaller but potentially critically important pool of human free plasma serotonin in platelet-poor plasma (PPP) has proven much more difficult, with a wide range of reference values reported. To characterize the available data we carried out a systematic literature search of previous reports of PPP serotonin and attempted to determine the best estimate of true PPP serotonin concentration in humans. A total of 101 published reports that included PPP serotonin values in healthy controls were found and included in the summary statistical analyses. The distribution of PPP serotonin values demonstrated high skewness (+1.98), and the reported values ranged from 0.6 to 179 nmol/L, with a mean of 31.6 nmol/L, an SD of 38.9 nmol/L, and a median of 14.8 nmol/L. Reported concentrations for human PPP or free plasma serotonin were highly discrepant, with most reports giving erroneously high values that should be disregarded. Inherent difficulties in selectively measuring the extremely low concentrations of serotonin present in PPP and in preparing PPP without contamination from platelet-derived serotonin contributed to the problem, as did the failure of researchers to compare their results with those from prior studies. There is a clear and pressing need for reference materials for the measurement of plasma (PPP) serotonin.

Serotonin Levels in Platelet-Poor Plasma and Whole Blood from Healthy Subjects: Relationship with Lipid Markers and Coronary Heart Disease Risk Score

The serotonin level in platelet-poor plasma (PPP) is an important clinical marker for monitoring platelet activation accompanying vascular endothelial injury. We previously developed an HPLC method that combines column-switching with a post-column reaction to measure serotonin in PPP. This study determined serotonin levels in healthy volunteers and evaluated the possible relationship of serotonin levels with lipid markers and Framingham 10-year risk scores (FRS) for coronary heart disease. Serotonin was isolated from samples using our HPLC method and converted into a fluorescent derivative with benzylamine for specific and sensitive detection. Lipid fractionation was also performed by HPLC. FRS was calculated using the following: age, sex, LDL cholesterol, HDL cholesterol, blood pressure, and smoking and diabetes status. The PPP serotonin to whole blood serotonin ratio (PPP/WB) and the PPP serotonin level correlated significantly with HDL cholesterol levels: r= 0.187, p< 0.05 and r= 0.184, p< 0.05, respectively. The PPP/WB ratio also correlated significantly with FRS (r= 0.176, p< 0.05). The reference range (95% confidence interval) of PPP and WB serotonin levels in healthy subjects were 0.86-16.96 and 385-1319 nmol/L, respectively. Significant positive correlations between the serotonin PPP/WB ratio and FRS suggest that the PPP/WB ratio can serve as a biomarker for estimating atherosclerotic cardiovascular risk.

Platelet poor plasma serotonin level in delinquent adolescents diagnosed with conduct disorder

Objective Accumulating data indicate the involvement of the serotonergic system in adolescent aggression. The aim of this study was to examine the platelet-poor plasma (PPP) serotonin (5-HT) levels among delinquent adolescent boys with conduct disorder (CD) in comparison with normal controls. Method PPP 5-HT levels were measured in 16 male delinquent CD adolescents from a correctional facility and in 14 normal male adolescent controls. Severity of aggressive behavior was assessed by the Child Behavior Checklist (CBCL) and the Overt Aggression Scale (OAS). Results Delinquent CD adolescents had higher PPP 5-HT levels (about 3-fold) than the normal controls (27.68 ± 32.29 vs. 7.76 ± 4.23 ng/ml, respectively, p = 0.027). In the delinquent CD adolescents a significant correlation was found between the PPP 5-HT levels and the CBCL and OAS aggressive scores ( r = 0.68, p = 0.0034 and r = 0.59, p = 0.016, respectively). Conclusions Juvenile delinquency is associated with high PPP 5-HT levels. Modulation of 5-HT neurotransmission may have a role in the symptomatology and treatment of severe adolescent CD.

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We thank Dr. Anderson for his comments regarding our article on plasma serotonin in autism [ [1] Connors S.L. Matteson K.J. Sega G.A. Lozzio C.B. Carroll R.C. Zimmerman A.W. Plasma serotonin in autism. Pediatr Neurol. 2006; 35: 182-186 Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar ], and recognize that we obtained much higher levels than those reported by Cook et al. [ [2] Cook Jr, E.H. Leventhal B.L. Freedman D.X. Free serotonin in plasma: Autistic children and their first-degree relatives. Biol Psychiatr. 1988; 24: 488-491 Abstract Full Text PDF PubMed Scopus (71) Google Scholar ]. Our intent in doing the study was not to replicate previous methodology to obtain free plasma serotonin or to focus on obtaining the exact range of values reported for platelet-poor plasma serotonin. Rather, we wanted to develop a replicable method that could clearly determine if any correlations existed between serotonin levels in the plasma of parents of autistic children and the autistic children themselves, and if differences existed between autism mothers and mothers of normal children. Also, we wanted the method to be one that was easily adapted and practical for the clinical laboratory. Measurement of Plasma Serotonin in AutismPediatric NeurologyVol. 36Issue 2PreviewIn the September 2006 issue of Pediatric Neurology, Connors et al. report observing substantially lower plasma serotonin levels in mothers of children with autism compared with control mothers [1]. Based on these observations, they conclude that “Low maternal plasma serotonin may be a risk factor for autism through effects on fetal brain development.” Unfortunately, the median values reported for controls and mothers of autistic children (∼250 ng/mL and 50 ng/mL, respectively) appear to be more than 100 times too high. Full-Text PDF

Plasma and platelet serotonin levels in patients with liver cirrhosis

To analyze the relationship between plasma and platelet serotonin levels and the degree of liver insufficiency. The prospective study included 30 patients with liver cirrhosis and 30 healthy controls. The degree of liver failure was assessed according to the Child-Pugh classification. Platelet and platelet poor plasma serotonin levels were determined. The mean plasma serotonin level was higher in liver cirrhosis patients than in healthy subjects (215.0 +/- 26.1 vs 63.1 +/- 18.1 nmol/L; P < 0.0001). The mean platelet serotonin content was not significantly different in patients with liver cirrhosis compared with healthy individuals (4.8 +/- 0.6; 4.2 +/- 0.3 nmol/platelet; P > 0.05). Plasma serotonin levels were significantly higher in Child-Pugh grade A/B than in grade C patients (246.8 +/- 35.0 vs 132.3 +/- 30.7 nmol/L; P < 0.05). However, platelet serotonin content was not significantly different between Child-Pugh grade C and grade A/B (4.6 +/- 0.7 vs 5.2 +/- 0.8 nmol/platelet; P > 0.05). Plasma serotonin levels are significantly higher in patients with cirrhosis than in the controls and represent the degree of liver insufficiency. In addition, platelet poor plasma serotonin estimation is a better marker for liver insufficiency than platelet serotonin content.

High-performance liquid chromatographic method with column-switching and post-column reaction for determination of serotonin levels in platelet-poor plasma

Objectives: Measurement of serotonin concentrations in blood is considered to be important for the clinical studies of diseases involving vascular endothelial injury. We have developed a high-performance liquid chromatographic (HPLC) method for measurement of serotonin level in platelet-poor plasma (PPP). Methods: Venous blood samples were collected using vacuum tubes containing ethylenediaminetetraacetic acid (EDTA) dipotassium salt; the optimum concentration in blood was 7.4 mmol/l. Serotonin in samples was separated by HPLC with a column-switching system, and was specifically converted into a fluorescent derivative with benzylamine for convenient detection. Results: The between-day assay coefficient of variation for a serotonin level (5.1 nmol/l) in PPP was 6.2%. The mean concentration of serotonin in PPP in healthy subjects was 5.7 ± 3.0 nmol/l. The serotonin levels in PPP in patients with ischemic heart disease were significantly higher than those in healthy subjects ( P = 0.001). Conclusions: The developed method had sufficient performance to determine serotonin levels in PPP from patients with ischemic heart disease.

A Novel Reporter Gene Assay to Determine Estrogen Receptor Activity in Primary Breast Cancer Cells

diarrhoea-predominant IBS with increased 5HT release but whether reduced release plays a role in causing constipation has not been examined. Aims: To determine the relationship between postprandial plasma serotonin release and colonic transit in C-IBS compared with PI-IBS and healthy controls. Methods: 15 C-IBS, 15 PI-IBS with diarrhoea predominant symptoms, and 15 healthy volunteers recruited through advertisement, underwent serial plasma serotonin measurement after a standard 520 kcal meal for 3 hours. Blood was taken through an 18G cannula into a syringe containing citrate, adenosine, dipyrimadole and theophylline to inhibit platelet activation. Platelet poor plasma (PPP) and platelet rich plasma (PRP) was assessed for 5-HT using H P K with electrochemical detection. Colonic transit was measured using marker pellets. Results: Mean (SEM) colonic transit was prolonged in C-IBS (49.4i3.8hrs) compared to PI-IBS (26.7e4.5) and controls (34.1d.5) ( ~ 4 . 0 0 2 ) . The area under the curve (AUC) of PPP serotonin from immediately after the meal to 180 minutes was lower in C-IBS (2593009nmoVL.min) compared to PI-IBS (5623i721) and controls (4822698) (p<O.OOI). Although PI-IBS showed increased AUC compared to controls these differences were not significant owing to substantial variability. There was a negative correlation between AUC and transit in all subjects ( ~ 0 . 3 5 4 , p=0.02). Platelet 5HT was greater in C-IBS (652k56.1) compared to PI-IBS (PRP= 484.1dO.7 ng/109 platelets), ~ 4 . 0 3 9 ) but not significantly different from controls (598.5i36.4) Conclusions: Reduced 5-HT release may be an important contributor to slow intestinal transit in C-IBS.

Psychopathology measured by established self-rating scales and correlated to serotonin measures in patients with fibromyalgia

The objective of the study was to evaluate the presence of psychopathology in fibromyalgia patients compared to a control group of rheumatic patients with pain. Forty-nine fibromyalgia patients and 33 controls were evaluated using established self-rating scales. Serotonin was determined using a radioenzymatic method. Fibromyalgia patients scored significantly higher than the controls on the majority of the subscales on the SCL-90, the two subscales on the Spielberger State and Trait Anxiety Inventory, the GHQ 12 scale and on a visual analogue pain scale. In a multivariate analysis the somatization dimension followed by the state anxiety accounted for the highest difference. Platelet-poor plasma serotonin, platelet serotonin and platelet uptake index were not significantly different between the groups. In conclusion, fibromyalgia patients presented quantitatively more psychopathology than the control group on a wide range of psychopathologic axes, and this cannot solely be accounted for by their higher level of pain.

Platelet-poor plasma serotonin in normal and preeclamptic pregnancy

We determined serotonin concentrations in platelet-poor plasma (PPP) from 11 preeclamptic pregnant women and 11 normal pregnant women by HPLC with electrochemical detection after a concentration step. Serotonin concentrations in PPP are very low in comparison with those in platelets, so it is very important to avoid in vitro release of serotonin from platelets. We therefore investigated three types of anticoagulants, the method of blood sampling, and the influence of whether the first or second 10 mL of blood is assayed. The type of anticoagulant proved to be important, K3-EDTA giving the best results. The serotonin concentrations in PPP from the preeclamptic pregnant women were significantly higher (P = 0.0001) than in the normal pregnant women: mean values +/- SD were 27.0 +/- 13.5 and 2.8 +/- 1.4 nmol/L, respectively. We suggest that the measurement of serotonin in PPP might be helpful in study of the role of serotonin in the development of preeclampsia.

Food preferences, body weight, and platelet-poor plasma serotonin and catecholamines

The possible relationship between body weight, food preferences, and plasma neurotransmitters was investigated in 96 healthy volunteers. The volunteers were divided into groups according to sex, body mass index, and food preferences. In all groups fasting platelet-poor plasma (PPP) norepinephrine and serotonin (5-HT) were examined. PPP-5-HT was low in obese individuals (mean +/- SD: 51.7 +/- 34.6 nmol/L) in comparison with lean individuals (94.31 +/- 85.2 nmol/L; P < 0.01), in lean male carbohydrate cravers (22.7 +/- 16.4 nmol/L) in comparison with protein cravers (132.9 +/- 80.6 nmol/L; P < 0.005) and noncravers (64.7 +/- 51.7 nmol/L; P < 0.05), and in obese male carbohydrate cravers (34 +/- 22.7 nmol/L) in comparison with obese male protein cravers (98.8 +/- 28.4 nmol/L; P < 0.001). In conclusion, PPP-5-HT might be seen as a peripheral indicator of processes linked with food consumption and food preferences.

Serotonin Concentrations in Plasma and Variations During the Menstrual Cycle

We used a specific and sensitive radioenzymatic method to establish a reference interval for the concentration of serotonin in platelet-poor plasma in 98 healthy volunteers (49 men, 49 women). The interval was 0-11 nmol/L with a median of 2.8 nmol/L. No difference in concentration in relation to sex or age was observed. In a group of eight very old volunteers (ages 86-92 years), however, concentrations were increased. In addition, we monitored the plasma concentrations of serotonin in 20 healthy women (ages 26-45 years) through two menstrual cycles. Periovulatory and premenstrual concentrations were greater than the serotonin concentration at the start of menstruation.

Evaluation of temporary liver dearterialization and embolization in patients with metastatic carcinoid tumour.

Patients with serotonin-containing metastatic midgut carcinoid tumours were treated with temporary liver dearterialization (19 patients) or liver embolization (8 patients). After 3, 6 and 12 months the effects of treatment were registered in changes in serotonin in platelet-poor plasma and blood, in urinary 5-HIAA, in tumour extent in the liver and in symptomatic relief. Seventeen patients, who underwent the dearterialization procedure survived the operation, while 2 patients who had a concomitant small bowel resection died of complications. Tumour response was obtained in 8 patients after 6 months and in 9 patients after 12. Stable disease was noted in 5 patients after 6 months and 3 patients after 12 months. Progressive disease was seen in 4 patients. All 19 patients except one exhibited the carcinoid syndrome prior to operation and 11 patients were free from symptoms for at least 12 months postoperatively. The gelatine foam powder liver embolization was performed uneventfully in all 8 patients. Tumour response was obtained in 3 patients at both 3 and 12 months. Stable disease was noted in 5 patients at 3 months and 4 patients at 12 months. Before embolization the patients suffered from the carcinoid syndrome and the treatment resulted in the immediate disappearance of the syndrome in 5 patients. After 12 months one patient was still free from obvious carcinoid symptoms. In one patient the disease aggravated in spite of treatment and he died 5 months after embolization. Thus, temporary liver dearterialization and liver embolization in midgut carcinoid patients resulted in tumour regression and symptomatic relief in 9 out of 19 patients and 3 out of 8 patients respectively. The complication rate was low.