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 (2.0–7.1 nmol/109 PLT) was elevated in 4/23 patients. None exhibited elevated intestinal permeability (lactulose/mannitol ratio: 0.008–0.035 mol/mol). PLT 5-HT did not correlate with intestinal permeability or GI tract complaints. PLT 5-HT correlated with 24 h urinary 5-hydroxyindoleacetic acid (5-HIAA; p = .034). Also urinary 5-HIAA and urinary 5-HT were interrelated (p = .005). A link between hyperserotonemia and increased intestinal permeability remained unsupported. Increased PLT 5-HT in PDD is likely to derive from increased PLT exposure to 5-HT. Longitudinal studies, showing the (in)consistency of abnormal intestinal permeability and PLT 5-HT, may resolve present discrepancies in the literature

Over de grens: Nederlands extreem geweld in de Indonesische onafhankelijkheidsoorlog, 1945-1949

Op 17 augustus 1945, twee dagen na de Japanse capitulatie, verklaarde Indonesië zich onafhankelijk. Nederland erkende dit niet en trachtte met geweld zelf de regie te voeren over het onvermijdelijke proces van dekolonisatie. Dit leidde tot vier jaren van moeizame onderhandelingen en bittere oorlogvoering. In 2005 verklaarde de Nederlandse regering dat Nederland die oorlog niet had moeten voeren. Over het geweld dat de Nederlandse militairen tijdens deze oorlog hadden toegepast, staat echter nog altijd het regeringsstandpunt uit 1969 overeind: er waren wel ‘excessen’, maar de krijgsmacht had zich in de regel ‘correct’ gedragen.Naarmate de aanwijzingen van extreem Nederlands geweld zich opstapelden, bleek dit officiële standpunt steeds moeilijker vol te houden. De Nederlandse regering besloot daarom in 2016 tot financiering van een groot onderzoeksprogramma. De belangrijkste conclusies daarvan zijn in dit boek te vinden. De auteurs maken aannemelijk dat de Nederlandse krijgsmacht op structurele basis extreem geweld toepaste en dat dit toen en ook lang daarna op allerlei manieren werd toegedekt. Dit alles past slecht bij een rooskleurig nationaal zelfbeeld – zoals eigenlijk de hele koloniale geschiedenis met dat zelfbeeld schuurt.Colonial and Global Histor

Long-term culture of genome-stable bipotent stem cells from adult human liver

Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy

The influence of ketoacids on plasma creatinine assays in diabetic ketoacidosis

OBJECTIVE: Analysis of the interference of ketoacids on various routine plasma creatinine assays during a clinical episode of diabetic ketoacidosis (DKA). DESIGN: Observational study. Blood samples were drawn before, during and after standard in-hospital treatment. Plasma creatinine was measured with two dissimilar enzymatic assays (creatininase PAP + and creatinine iminohydrolase Serapak), a kinetic alkaline picrate method (Jaffé) and a high-performance liquid chromatography (HPLC) procedure. Acetoacetate and beta-hydroxybutyrate were analysed by enzymatic methods. SETTING: Department of Medicine, University Hospital. SUBJECTS: Nine patients who experienced 10 episodes of DKA. MAIN OUTCOME MEASURES: Agreement of the routine plasma creatinine assays with HPLC and analysis of possible interferents. RESULTS: At presentation, the Jaffé assay gave falsely high values of plasma creatinine (median 99 micromol L(-1)), in contrast to the PAP+ (median 60.5 micromol L(-1)) and HPLC assays (median 67.5 micromol L(-1)). This positive error decreased during treatment. This was due to a decrease in acetoacetate, as the positive error by the Jaffé method correlated with the acetoacetate concentration (r = 0.79, P < 0.0001). In the multiple regression analysis, beta-hydroxybutyrate caused no additional interference by the Jaffé assay, confirmed by in vitro experiments. Analysis of agreement showed that the difference between PAP+ and HPLC creatinine was -4.6 +/- 3.0 micromol L(-1) (mean +/- SD), and 2.0 +/- 5.3 micromol L(-1) between Serapak and HPLC. This was statistically significant, but clinically negligible. CONCLUSION: Acetoacetate caused severe interference of the alkaline picrate (Jaffé) assay, which might influence therapeutic decisions at the start of diabetic ketoacidosis. Enzymatic assays lack this interferenc

Follow-up of GFR estimated from plasma creatinine after cimetidine administration in patients with diabetes mellitus type 2

BACKGROUND: The glomerular filtration rate (GFR) can be estimated from plasma creatinine according to the formula of Cockcroft and Gault (CG). When tubular secretion of creatinine is inhibited by cimetidine the mean difference between the Cockcroft-Gault clearance (CG(Cim) and GFR approximates zero, but there is still some interindividual difference, especially in type-2-diabetic patients. We studied during longitudinal follow-up, whether the discrepancies between CG(Cim) and GFR per patient are consistent in time in type-2-diabetic patients. PATIENTS AND METHODS: In 1996 and 1998 (interval 20-26 months) GFR was measured in 21 patients as the urinary clearance of continuously infused 125I-iothalamate. Plasma creatinine was analyzed with an enzymatic assay before and after oral cimetidine 800 mg t.i.d. during 24 hours. GFR estimations were calculated with the Cockcroft-Gault formula before (CG) and after cimetidine (CG(Cim)) and expressed as means +/- SEM. RESULTS: GFR deteriorated from 89.7 +/- 5.7 to 81.3 + 5.8 ml/min/1.73 m2 and CG(Cim) from 85.3 +/- 5.7 to 81.1 +/- 6.6 ml/min/1.73 m2, whereas CG decreased from 102.4 +/- 6.8 to 98.4 +/- 7.0 ml/min/1.73 m2. Changes in GFR and changes in CG(Cim) were correlated (r = 0.72, p < 0.001) and were not significantly different from each other. The discrepancy between CG(Cim) and GFR per patient in 1996 also correlated with the discrepancy between CG(Cim) and GFR in 1998 (r = 0.85, p < 0.001 ). CONCLUSIONS: In individual patients the discrepancies between the CG(Cim) and GFR are consistent in time and the change in GFR is reflected by the change in CG(Cim). This small variability means that CG(Cim), based on an enzymatic plasma creatinine assay, would be suitable for follow-up of GFR in type-2-diabetic patients, independent of albuminuri

Continuous ambulatory peritoneal dialysis (CAPD) in patients with diabetic nephropathy

A 3-centre study was done to analyse the results of 70 patients with end-stage renal disease caused by diabetic nephropathy and treated with CAPD. Fifty patients had insulin-dependent diabetes (mean age 42, mean duration of diabetes 24 yr); 20 had non-insulin-dependent diabetes (mean age 61, mean duration 15 yr). Total treatment time was 1563 months and ranged from one to 83 months (median 18). Patient survival was 86% at 1 yr and 33% at 4 yr. Technique survival was 87% and 63%. Cox's multiple hazard regression analysis showed that age above 45 yr (relative risk 2.2), systolic hypertension (2.6) and cardiac disease (2.2) at the start of CAPD were associated with shorter patient survival. Metabolic control was good. Haemoglobin rose during the first 3 months. Plasma creatinine concentration increased with time, probably due to the loss of residual renal function. HbA1c levels were in the normal range for 60% of the patients. Mean hospital stay was 42 days per year, 26 as a consequence of vascular complications and 16 due to peritonitis and catheter-related problems. We conclude that CAPD is a good renal replacement modality for patients with diabetic renal failure. The patient survival is dependent on age, systolic hypertension and cardiac disease at the start of CAP