Plant sterols cause macrothrombocytopenia in a mouse model of sitosterolemia.

Mutations in either ABCG5 or ABCG8 cause sitosterolemia, an inborn error of metabolism characterized by high plasma plant sterol concentrations. Recently, macrothrombocytopenia was described in a number of sitosterolemia patients, linking hematological dysfunction to disturbed sterol metabolism. Here, we demonstrate that macrothrombocytopenia is an intrinsic feature of murine sitosterolemia.

Persistent low urinary excretion of 5-HIAA is a marker for favourable survival during follow-up in patients with disseminated midgut carcinoid tumours.

Survival of patients with disseminated midgut carcinoid tumours varies. We investigated which factors predict survival at referral and during follow-up, with emphasis on urinary 5-hydroxyindolacetic acid (5-HIAA) levels. Between 1992 and 2003, 76 patients were studied; urine was prospectively collected over a 24 h period every 3 months in order to measure 5-HIAA levels.

Angptl4 upregulates cholesterol synthesis in liver via inhibition of LPL- and HL-dependent hepatic cholesterol uptake.

Background: Dysregulation of plasma lipoprotein levels may increase the risk for atherosclerosis. Recently, angiopoietin-like protein 4, also known as fasting-induced adipose factor Fiaf, was uncovered as a novel modulator of plasma lipoprotein metabolism. Here we take advantage of the fasting-dependent phenotype of Angptl4-transgenic (Angptl4-Tg) mice to better characterize the metabolic function of Angptl4.

Plasma free metanephrine measurement using automated online solid-phase extraction HPLC tandem mass spectrometry.

Background: Quantification of plasma free metanephrine (MN) and normetanephrine (NMN) is considered to be the most accurate test for the clinical chemical diagnosis of pheochromocytoma and follow-up of pheochromocytoma patients. Current methods involve laborious, time-consuming, offline sample preparation, coupled with relatively nonspecific detection. Our aim was to develop a rapid, sensitive, and highly selective automated method for plasma free MNs in the nanomole per liter range.

Brief report: normal intestinal permeability at elevated platelet serotonin levels in a subgroup of children with pervasive developmental disorders in Curaçao (The Netherlands antilles).

This study investigated the relationship between platelet (PLT) serotonin (5-HT) and intestinal permeability in children with pervasive developmental disorders (PDD). Differential sugar absorption and PLT 5-HT were determined in 23 children with PDD. PLT 5-HT (2.

Apparent loss of urinary albumin during long-term frozen storage: HPLC vs immunonephelometry.

Background: Urinary albumin detection by immunonephelometry is decreased by approximately 30% in samples that have been frozen at -20 degrees C. An HPLC method for assessment of urinary albumin that detects immunoreactive and immunochemically nonreactive albumin has been introduced as an alternative to immunonephelometry. We investigated whether this technique is affected by sample temperature, particularly freezing.

Catechol-o-methyltransferase polymorphism and susceptibility to major depressive disorder modulates psychological stress response.

Objectives: The stress response is related to both physiological and psychological factors and is strongly marked by a neuroendocrine component. Genetic factors are believed to underlie individual differences in the degree of stress resilience and thereby contribute in determining susceptibility to stress-related pathologies like major depressive disorder (MDD). Little, however, is known about the genetic influence on the endocrine and behavioural stress response in relation to MDD.

Biochemical markers in the follow-up of medullary thyroid cancer.

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard tumor marker calcitonin, plasma carcino-embryonic antigen (CEA), plasma catecholamines, (platelet) serotonin, chromogranin A, tryptase, and urinary markers of catecholamine, histamine, and serotonin metabolism were prospectively determined in 46 patients with histologically proven MTC.

Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study.

Background: To assess individual treatment options for patients with carcinoid tumours, accurate knowledge of tumour localisation is essential. We aimed to test the diagnostic sensitivity of 6-[fluoride-18]fluoro-levodopa ((18)F-DOPA PET), compared with conventional imaging methods, in patients with carcinoid tumours.

Methods: In a prospective, single-centre, diagnostic accuracy study, (18)F-DOPA PET with carbidopa pretreatment was compared with somatostatin-receptor scintigraphy (SRS), CT, and combined SRS and CT in 53 patients with a metastatic carcinoid tumour.

Intravenous tissue plasminogen activator in patients with stroke increases the bioavailability of insulin-like growth factor-1.

Background And Purpose: Insulin-like growth factor (IGF)-1 has potent neuroprotective properties. We investigated the effects of intravenous administration of tissue plasminogen activator (tPA) on serum levels of IGF-1 and IGF-binding protein (IGFBP)-3 in patients with acute ischemic stroke.

Methods: Serum levels of total IGF-1, free IGF-1, and IGFBP-3 were measured by radioimmunoassay in 10 patients with ischemic stroke treated with intravenous tPA (0.

Iodine-123 metaiodobenzylguanidine scintigraphy in localising phaeochromocytomas--experience and meta-analysis.

Background: Recommendations on the use of I-123 metaiodobenzylguanidine (MIBG) scintigraphy in localising phaeochromocytomas vary. The accuracy of I-123 MIBG scintigraphy was determined by evaluating our own I-123 MIBG scans and performing a meta-analysis.

Materials And Methods: Between January 1992 and May 2002, the I-123 MIBG scans of consecutive patients suspected of a phaeochromocytoma were re-evaluated.

Clinical utility of an automated immunochemiluminometric thyroglobulin assay in differentiated thyroid carcinoma.

Background: Thyroglobulin (Tg) measurements are important in the follow-up of patients with differentiated thyroid carcinoma (DTC). We evaluated the analytical and clinical performance of a new automated immunochemiluminometric assay for Tg (Tg-ICMA; Nichols Advantage Tg; Nichols Institute Diagnostics).

Methods: We used the Tg-ICMA to measure Tg concentrations in serum samples from 110 Tg antibody-negative DTC patients undergoing thyroid-hormone suppression therapy.

Irritability rather than depression during interferon treatment is linked to increased tryptophan catabolism.

Objective: Treatment with recombinant interferon is associated with high rates of psychiatric comorbidity. We investigated the relation between catabolism of the essential amino acid tryptophan, being rate-limiting of peripheral and cerebral serotonin formation, and psychiatric symptoms in patients undergoing combination treatment with interferon-alpha and ribavirin.

Patients And Methods: Eighteen patients with viral hepatitis C who received interferon were included.

Abdominal angina in patients with a midgut carcinoid, a sign of severe pathology.

In 36 consecutive patients with a foregut carcinoid with extensive local tumor growth and liver metastases with a carcinoid syndrome, six patients had complaints of postprandial abdominal pain and attacks of subileus based on segmental intestinal ischemia. A diagnosis of abdominal angina was supported by a positive response to nitroglycerin in two and ischemia of the ileum demonstrated by angiography in two other patients. Complaints were reduced in all patients after surgery.

Automated on-line solid-phase extraction coupled with HPLC for measurement of 5-hydroxyindole-3-acetic acid in urine.

Background: Quantification of 5-hydroxyindole-3-acetic acid (5-HIAA) in urine is useful in diagnosing and monitoring of patients with carcinoid tumors and in the study of serotonin (5-hydroxytryptamine) metabolism in various disorders. We describe an automated method that incorporates on-line solid-phase extraction (SPE) and HPLC to measure urinary 5-HIAA.

Methods: Automated prepurification of urine was accomplished with HySphere-resin GP SPE cartridges containing strong hydrophobic polystyrene resin.

Protease activity of plasma hemopexin.

Background: Previous studies into the relevance of a putative circulating factor in the pathogenesis of minimal change nephrotic syndrome have opened the possibility that plasma hemopexin might be an important effector molecule in this disorder. Thus, intra renal infusion of isolated plasma hemopexin into rats induced minimal change like glomerular lesions and proteinuria. Both, in vivo and in vitro effects of the active isoform of hemopexin could be attributed to protease activity of this molecule.

Carcinoid crisis after injection of 6-18F-fluorodihydroxyphenylalanine in a patient with metastatic carcinoid.

A carcinoid crisis is a severe complication of the carcinoid syndrome that can arise in patients with advanced metastatic neuroendocrine tumors. It can be initiated by stress, catecholamines, and tumor manipulation. In this article, we report a case in which an injection with the catecholamine tracer 6-18F-fluorodihydroxyphenylalanine, used for PET, induced a carcinoid crisis.

Discovery and consequences of apolipoprotein-epsilon(3Groningen): a G-insertion in codon 95/96 that is predicted to cause a premature stop codon.

Background: We found an unexplained, persistent discrepancy between the outcomes of two apolipoprotein-E (apo-E) genotyping methods for a patient with features of familial dysbetalipoproteinaemia (FD). Polymerase chain reaction - restriction fragment length polymorphism resulted in the apo-epsilon(2)/epsilon(2) genotype, whereas minisequencing indicated apo-epsilon(2)/epsilon(3). The discrepancy was predicted to derive from a novel mutation.

Serotonin signaling is a very early step in patterning of the left-right axis in chick and frog embryos.

Background: Consistent left-right (LR) asymmetry is a fascinating problem in developmental and evolutionary biology. Conservation of early LR patterning steps among vertebrates as well as involvement of nonprotein small-molecule messengers are very poorly understood. Serotonin (5-HT) is a key neurotransmitter with crucial roles in physiology and cognition.

Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder.

Two putatively functional polymorphisms of the serotonin transporter gene (HTT, SLC6A4) were examined for associations with risk for pervasive developmental disorders (PDDs) and specific autism phenotypes. Dutch patients diagnosed with PDD (N = 125, age range 5-20 years, DSM-IV-TR based criteria, ADI-R and ADOS behavioral assessments) and their parents (N = 230) were genotyped for promoter ins/del (5-HTTLPR) and intron 2 variable number of tandem repeats (VNTR) alleles. Using the transmission disequilibrium test (TDT), no disorder-specific preferential transmission of promoter (long and short) or intron 2 (10- and 12-repeat) alleles was observed.

Which method for quantifying urinary albumin excretion gives what outcome? A comparison of immunonephelometry with HPLC.

Background: Microalbuminuria has recently been identified as an independent risk factor for cardiovascular disease in the general population. Immunochemical urinary albumin assays only detect immunoreactive intact albumin. High performance liquid chromatography (HPLC) is able to detect both immunoreactive and immunounreactive intact albumin.

Complications of midgut carcinoid tumors and carcinoid syndrome.

The carcinoid syndrome, associated with carcinoid tumors of the midgut, consists of symptoms such as diarrhea, flushing, wheezing and cardiovascular symptoms. This review focuses on these symptoms and discusses therapeutic options. The symptoms are caused by the secretion of biogenic amines, polypeptides and other factors of which serotonin is the most prominent.