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Biomedical subjects

J Møller

Publications and source records attributed to J Møller.

At least 37 records · Page 2Linked to original sources

Effects of oral glucose on systemic glucose metabolism during hyperinsulinemic hypoglycemia in normal man.

The widespread use of oral glucose in the treatment of hypoglycemia is mainly empirically based, and little is known about the time lag and subsequent magnitude of effects following its administration. To define the systemic impact and time course of effects following oral glucose during hypoglycemia, we investigated 7 healthy young men twice. On both occasions, a 6-hour hyperinsulinemic (1.5 mU/kg/min)-hypoglycemic clamp was performed to ensure similar plasma glucose profiles during a stepwise decrease toward a nadir less than 50 mg/100 mL after 3 hours. On the first occasion, subjects ingested 40 g glucose and 4 g 3-ortho-methylglucose ([3-OMG] to trace glucose absorption) dissolved in 400 mL tap water after 3.5 hours. The second examination was identical except for the omission of 40 g oral glucose, and glucose levels were clamped at hypoglycemic concentrations similar to those recorded on the first examination. Plasma glucose curves were superimposable, and all participants reached a nadir less than 50 mg/100 mL. Similar increases in growth hormone (GH) and glucagon were observed in both situations. The glucose infusion rates (GIRs) were lower after oral glucose, with the difference starting after 5 to 10 minutes, being statistically significant after 20 minutes, and reaching a maximum of 8.5 +/- 1.6 mg/kg/min after 40 minutes. Circulating 3-OMG increased after 20 minutes. In both situations, infusion of insulin resulted in insulin levels of approximately 150 microU/mL and a suppression of C-peptide levels from 2.0 to 1.1 nmol/L (P < .01). After glucose ingestion, both serum C-peptide and glucagon-like peptide-1 (GLP-1) increased (C-peptide from 1.1 +/- 0.05 to 1.4 +/- 0.05 nmol/L and GLP-1 from 3.2 +/- 0.8 to 18.1 +/- 3.3 pmol/L), in contrast to the situation without oral glucose (P < .05). Isotopically determined glucose turnover was similar. In conclusion, our data suggest that oral glucose affects systemic glucose metabolism rapidly after 5 to 10 minutes. Quantitatively, the immediate impact is relatively small, with the gross impact observed after approximately 40 minutes. Future studies aiming to identify therapeutic oral agents with prompt effect seem warranted.

Administration, Oral↗

A meta-analysis of cerebrovascular disease and hyperhomocysteinaemia.

Hyperhomocysteinaemia has been identified as a risk factor for stroke and cerebrovascular disease in several studies. To evaluate the evidence we performed a meta-analysis. We found 21 studies searching Medline from 1966-July 1999 using the key words homocysteine, homocystine and cerebrovascular disease or stroke combined with a search of Embase, Science Citation Index and Biological Abstract. In 17 of these studies the populations were comparable. The studies were divided into two groups, cross-sectional studies and longitudinal studies where a pre-insult plasma or serum total homocysteine was used. The reports on 8 cross-sectional and 4 longitudinal studies gave data on the mean and standard deviations of plasma or serum homocysteine for both cases and controls, and these studies were included in the meta-analysis. The results of the 5 excluded studies all pointed to a positive relationship between hyperhomocysteinaemia and cerebrovascular disease. For each study, the expected fractions of the cases with total homocysteine higher than the 95-percentile for the controls were calculated, using the means and standard deviations, assuming a log-normal distribution, and the odds-ratios for disease with total homocysteine above the 95-percentile were computed. The overall weighted odds-ratio for disease with a concentration of homocysteine in plasma or serum above the 95-percentile (95% confidence interval) for the cross-sectional studies was 4.12 (2.94-5.77), for the longitudinal studies 3.74 (2.53-5.54), and for all 12 studies 3.97 (3.07-5.12). In conclusion, the results support the case for a strong relation between hyperhomocysteinaemia and cerebrovascular disease.

Cerebrovascular Disorders↗

Adenosine is an agonist of the growth hormone secretagogue receptor.

Growth hormone secretagogues (GHSs) are synthetic compounds that induce GH release in several species, including man. The aim of the current study was to identify hypothalamic GHS receptor (GHS-R) agonists. This led to the discovery of adenosine as a GHS-R agonist. We demonstrate that adenosine as well as the A1 adenosine receptor agonist N6-R-phenylisopropyladenosine (R-PIA) induce calcium responses, with EC50 values of 50 nM and 0.5 nM, respectively, in cells which express recombinant human GHS-R. However, neither compound induces a calcium response in nontransfected cells. Binding experiments show that adenosine and the GHS compound MK-0677 bind to membranes from GHS-R expressing cells with nearly identical Bmax values (2.6 +/- 0.1 x 10(-10) mol/mg protein for adenosine and 2.0 +/- 0.3 x 10(-10) mol/mg protein for MK-0677). However, no binding to membranes from nontransfected cells could be detected. Furthermore, we show that the IC50 values for inhibition of the adenosine, R-PIA, and GHS induced calcium responses by the GHS-R antagonist [D-Arg1, D-Phe5, D-Trp7,9, D-Leu11]-substance P are similar. These findings strongly suggest that adenosine and R-PIA are agonists of the GHS-R. Interestingly, neither adenosine nor R-PIA were able to induce GH release from rat pituitary cells in vitro. The implications of the latter finding is discussed.

Adenosine↗

Evaluation of novel assays in clinical chemistry: quantification of plasma total homocysteine.

BACKGROUND: There is a need for systematic evaluation of methods before their release to the market. We addressed this problem in novel homocysteine assays as part of an European Demonstration Project involving six centers in four countries. METHODS: Two immunological methods for measurement of plasma total homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas chromatography-mass spectrometry (GC-MS). All laboratories performed the following procedures: (a) familiarization; (b) determination of linearity and precision by analyzing five plasma samples with interrelated concentrations for 20 days; (c) correlation using patients' samples; and (d) assessment of long-term performance. RESULTS: Both immunological methods were linear for P-tHcy between 5 and 45 micromol/L. The intralaboratory imprecision (CV) was <5% for FPIA and <9% for EIA used with a sample processor. The bias was -2% to 3% for FPIA and 2-4% for EIA used with a sample processor. CONCLUSIONS: The immunological methods provide results with little bias compared with HPLC and GC-MS. The imprecision of the assays must be considered in the context of their intended use(s).

Fluorescence Polarization Immunoassay↗

Effects of a 7-day continuous infusion of octreotide on circulating levels of growth factors and binding proteins in growth hormone (GH)-treated GH-deficient patients.

In patients with acromegaly, clinical improvement has been reported after octreotide (OCT) treatment, even in cases of only a moderate suppression of growth hormone (GH) levels. In rats, OCT suppresses IGF-I mRNA expression and generation of serum and tissue IGF-I levels. A direct effect of OCT on the IGF system could have therapeutical implications in diabetes mellitus, cardiovascular disease, and certain malignancies in which IGF-I might be involved. The aim of this study was to examine possible GH-independent effects of OCT on IGF components in humans. Six GH-deficient (GHD) patients were studied for 24 h after each of the following treatment regimens (each of 1 weeks duration): (a) daily s.c. GH injection (2 IU/m(2)); (b) as (a) + continuous s.c. infusion of OCT (200 microg/24 h) by means of a portable pump (Nordic Infuser); (c) no treatment. Serum GH binding protein (GHBP) levels tended to be lower after GH and OCT than after GH alone (P =0.10). OCT reduced the GH induced increase in serum IGF-I levels (P<0.05, ANOVA). Mean integrated levels (microg/l) were 359.1+/-49.6 (GH), and 301.6+/-58.9 (GH+OCT). OCT did not significantly reduce serum IGFBP-3 levels (microg/l) [3460+/-270 (GH), and 3112+/-435 (GH+/-OCT);P =0.14]. Serum levels of free IGF-I (P =0.39), IGF-II (P =0.54), and of the acid-labile subunit (ALS) of the ternary complex (P =0.50) were similar during GH+/-OCT as compared with GH alone. After 1 week off GH treatment, significantly lower levels of IGF-I, IGF-II, IGFBP-3, and ALS were recorded (P<0.001). Serum IGFBP-1 levels were significantly higher after GH+OCT than after GH alone (P<0.0001), and levels were even higher without GH. Serum insulin levels (pmol/l) were significantly higher after GH alone as compared with no GH (P<0.05, ANOVA), whereas OCT partly suppressed the insulinotropic effect of GH (P<0. 05) [mean: 114.5+/-33.0 (GH), 91.3+/-29.6 (GH+OCT), 65.9+/-22.5 (no GH)]. This was also reflected in higher blood glucose levels during GH+OCT. Finally, GH+OCT reduced glucagon levels significantly as compared with GH alone (P =0.02). In conclusion, 7 days' administration of OCT to GH-treated GHD patients slightly attenuated serum IGF-I generation, and tended to decrease levels of the other components of the 150 kDa ternary complex. Whether these effects are mediated directly by OCT or indirectly via the accompanying changes in insulin levels remains to be investigated.

Adult↗

Thrombophilic predisposition in stroke and venous thromboembolism in Danish patients.

The present study describes 403 patients with thrombosis, from a uniform ethnic and geographical background. Two-hundred-and-seven individuals had suffered mild or moderate stroke and 196 individuals suffered venous thromboembolism. We recorded levels of antithrombin, protein C and protein S, plasminogen and plasma homocysteine, and the presence of the factor V Leiden mutation, the prothrombin 20210G-->A variant, and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism. Controls for the mutation frequencies consisted of Guthrie card blood spots from a cohort of new-born babies. The cumulative prevalence of deficiencies in antithrombin, protein C, protein S or plasminogen was 2.4% in patients with stroke and 11.2% in patients with venous thrombosis. The factor V Leiden mutation was present in 11.1% of patients with stroke and 26.5% of patients with venous thrombosis, compared with 6.6% of controls (n = 4188; P < 0.05 and P < 0.0001, respectively). The prevalence of the prothrombin 20210A variant was 3.1% in patients with venous thrombosis, 1.9% in patients with stroke and 2.0% in controls (n = 500; P > 0.05). Hyperhomocysteinemia was present in 16.0% of patients with stroke and 17.6% of patients with venous thrombosis. The prevalence of the MTHFR 677T/T genotype was no different in patients with stroke (10.6%) and venous thrombosis (8.7%) than in controls (8.3%; n = 1084; P > 0.05); thus, it apparently contributed to thrombosis only via its influence on total plasma homocysteine, which was significantly increased in patients with the T/T genotype (P < 0.001). The MTHFR T/T genotype did not further increase the risk for thrombosis in carriers of the factor V Leiden mutation. Overall, thrombotic events were associated with a known risk factor in 27% of patients with stroke and 55% of patients with venous thrombosis.

Adolescent↗

Growth hormone and fluid retention.

A major side effect of growth hormone (GH) administration is fluid retention. Most data indicate that adult GH-deficient patients are dehydrated, i.e. they have low total body water, low extracellular water and low plasma volume. When GH substitution is initiated in these patients their body fluid compartments are restored to normal. The fluid retaining capacity of GH should therefore be regarded as a desirable physiological normalization of fluid homeostasis rather than an unpleasant side effect.

Adult↗

Long-term effects of growth hormone (GH) on body fluid distribution in GH deficient adults: a four months double blind placebo controlled trial.

OBJECTIVE: Short-term growth hormone (GH) treatment normalises body fluid distribution in adult GH deficient patients, but the impact of long-term treatment on body fluid homeostasis has hitherto not been thoroughly examined in placebo controlled trials. To investigate if the water retaining effect of GH persists for a longer time we examined the impact of 4 months GH treatment on extracellular volume (ECV) and plasma volume (PV) in GH deficient adults. DESIGN: Twenty-four (18 male, 6 female) adult GH deficient patients aged 25-64 years were included and received either GH (n=11) or placebo (n=13) in a double blind parallel design. METHODS: Before and at the end of each 4 month period ECV and PV were assessed directly using 82Br- and 125I-albumin respectively, and blood samples were obtained. RESULTS: During GH treatment ECV increased significantly (before: 20.48+/-0.99 l, 4 months: 23.77+/-1.38 l (P<0.01)), but remained unchanged during placebo administration (before: 16.92+/-1.01 l, 4 months: 17.60+/-1.24 l (P=0.37)). The difference between the groups was significant (P<0.05). GH treatment also increased PV (before: 3.39+/-0.27 l. 4 months: 3.71+/-0.261 (P=0.01)), although an insignificant increase in the placebo treated patients (before: 2.81+/-0.18 l, 4 months: 2.89+/-0.20 l (P=0.37)) resulted in an insignificant treatment effect (P=0.07). Serum insulin-like growth factor-I increased significantly during GH treatment and was not affected by placebo treatment. Plasma renin (mIU/l) increased during GH administration (before: 14.73+/-2.16, 4 months: 26.00+/-6.22 (P=0.03)) and remained unchanged following placebo (before: 20.77+/-5.13, 4 months: 20.69+/-6.67 (P=0.99)) leaving no significant treatment effect (P=0.08). CONCLUSION: The long-term impact of GH treatment on body fluid distribution in adult GH deficient patients involves expansion of ECV and probably also PV. These data substantiate the role of GH as a regulator of fluid homeostasis in adult GH deficiency.

Adult↗

External quality assessment of methylmalonic acid and total homocysteine.

BACKGROUND: The use of analyses for methylmalonic acid (MMA) and total homocysteine (HCY) in plasma has become widespread. Realizing the need for external quality assessment for these measurements, we started a program in 1997. The results for 1998 are reviewed in this report. METHODS: Fourteen laboratories participated with 15 sets of results for MMA, and 28 laboratories participated with 34 sets of results for HCY. Results for four identical samples, made up from the same unmodified serum (MMA) or EDTA-plasma (HCY) pool, sent out under different identifications, were used for assessing the imprecision. Samples made up from the same pools supplemented with MMA or L-HCY to three concentrations were used for assessing the recovery. By using literature data for the biological variation, quality goals for both analytes were calculated. RESULTS: The overall within-laboratory CV was 12% for MMA and 7.5% for HCY. Gas chromatography-mass spectrometric HCY results had lower imprecision than the HPLC or immunoassay results. For MMA, no significant between-laboratory component of variance was found. Only results for HCY obtained with HPLC methods showed significant between-laboratory variance. CONCLUSIONS: Eight of the 15 participants achieved the minimum imprecision goal for MMA vs 9 of the 34 participants for HCY. The minimum quality goals for bias as approximated by the recovery were achieved by 13 participants for MMA and 26 for HCY.

Chromatography, High Pressure Liquid↗

Growth hormone treatment improves body fluid distribution in patients undergoing elective abdominal surgery.

OBJECTIVE: To investigate the possible beneficial effects of growth hormone (GH) in catabolic patients we examined the impact of GH on body fluid distribution in patients with ulcerative colitis undergoing elective abdominal surgery. DESIGN AND MEASUREMENTS: Twenty-four patients (14 female, 10 male) aged 19-47 years were in a double-blinded study randomly assigned to receive either placebo (n = 12) or GH (n = 12) 6 i.u. s.c. twice daily from 2 days before until 7 days after ileo-anal J pouch surgery. Extracellular and plasma volume (ECV, PV) were determined using 82Br and 125I albumin dilution at day -2 and at day 7, and body composition was estimated by dual X-ray absorptiometry and bioimpedance. Changes in body weight and fluid balance were recorded and hence intracellular volume was assessed. RESULTS: During placebo treatment body weight decreased 4.3 +/- 0.6 kg; during GH treatment body weight was constant (P < 0.01). There was a positive fluid balance in the GH-treated patients compared to the placebo group (GH: 3.6 +/- 0.7 l; plc: -0.7 +/- 1.2 l, P < 0.01). ECV increased 2.12 +/- 0.70 l during GH and was unaffected during placebo (P = 0.02). PV was unchanged by GH and decreased 0.39 +/- 0.08 l during placebo administration (P = 0.03). Intracellular volume (ICV) decreased less during GH than during placebo (GH: -1.42 +/- 0.45; plc: -3.70 +/- 0.76; P = 0.02). Bioimpedance remained constant during GH administration and increased 60 +/- 9 ohm in the placebo-treated group (P < 0.05). Plasma renin and aldosterone remained unchanged in both study groups. CONCLUSION: Body weight, plasma volume and intracellular volume is preserved during GH treatment in catabolic patients and ECV is increased. From a therapeutic point of view these effects may be desirable under conditions of surgical stress.

Adult↗

An outbreak of Pontiac fever among children following use of a whirlpool.

We investigated an outbreak of fever, most likely due to a contaminated whirlpool, among nine adults and six children residing in a summerhouse. The outbreak was characterized by a high attack rate, short incubation periods, influenza-like symptoms, and rapid recoveries, all features typical of Pontiac fever. However, the children had less-characteristic symptoms than the adults, and they did not have any sequelae. Findings on the children's chest radiographs were unremarkable, and none of the children had leukocytosis. Evidence of Legionella pneumophila infection was found in six cases: in one case by isolation of L. pneumophila serogroup 1 and detection of legionellae by PCR, and in five cases by seroconversion to the clinical isolate. Six additional cases had presumptive evidence of legionella infection, with seroconversion to Legionella micdadei antigen; a PCR assay was also positive for legionellae for one of these cases. In contrast, two adult nonusers of the whirlpool had no symptoms and no serological evidence of infection. Serological testing and cultures for other pathogens, as well as cultures of all environmental samples, were negative. This investigation demonstrates the differences between adults and children with respect to the clinical picture of Pontiac fever; furthermore, it shows that culture and PCR assay of tracheal aspirates for legionellae can be performed in a hospital setting for rapid diagnosis, although the sensitivities of these methods are low.

Adult↗

Percutaneous dilatational tracheostomy versus conventional surgical tracheostomy. A clinical randomised study.

BACKGROUND: As no clinical randomised studies have previously been performed comparing complications with the Ciaglia Percutaneous Dilatational Tracheostomy Introducer Set (PDT) and conventional surgical tracheostomy (TR), we designed a study with the aim of comparing the efficacy and safety of the two techniques. METHODS: Sixty patients selected for elective tracheostomy were randomised for either PDT (30 patients) or TR (30 patients). All patients had general anaesthesia and were ventilated with 100% oxygen. Furthermore, lidocaine with epinephrine 1% (3-5 ml) was used for local analgesia and to minimise bleeding during the procedure. RESULTS: The median time for insertion of the tracheostomy tube was 11.5 min (range 7-24 min) in the PDT group and 15 min (range 5-47 min) in the TR group (P<0.01). Complications during the procedure were cuff puncture of the endotracheal tube in 5 cases in the PDT group. Minor bleeding was encountered in 6 cases in the PDT group as opposed to 24 cases in the TR group (P<0.01), major bleeding in none versus 2 cases, respectively. In 8 cases in the PDT group, increased resistance to insertion of the tracheostomy tube was met by further dilatation. During the post-tracheostomy period, complications occurred with minor bleeding in 2 cases in the PDT group as opposed to 9 cases in the TR group (P<0.05), and major bleeding was encountered in 1 case in each group. Minor infections were encountered in 3 cases in the PDT group as opposed to 11 cases in the TR group (P<0.01). Major infection was encountered in none versus 8 cases, respectively (P<0.01). CONCLUSION: Our results indicate that the percutaneous dilatational tracheostomy technique performed with the Ciaglia Introducer Set is effective, safe and superior to conventional surgical tracheostomy as immediate complications as well as complications with the tracheostomy tube in situ are fewer and of less severity.

Adolescent↗

No effect of growth hormone on serum insulin-like growth factor binding protein-3 proteolysis.

Increased proteolysis of insulin-like growth factor binding protein (IGFBP)-3 is seen in several pathophysiological conditions and may represent an important mechanism for the regulation of insulin-like growth factor bioavailability. It has previously been suggested that proteolysis of IGFBP-3 is dependent on the GH status. To investigate this, IGFBP-3 proteolysis was measured in three groups of subjects: 1) GH-deficient patients before and after GH replacement (n = 14); 2) healthy subjects before and after 14 days of GH administration (n = 7); and 3) acromegalic patients before and after treatment with a long-acting SRIH analogue (octreotide; n = 14). In vivo IGFBP-3 proteolysis was investigated by Western immunoblotting. No difference was detected in pretreatment samples, and GH treatment in GH-deficient subjects or octreotide treatment in acromegalic subjects had no impact on in vivo proteolysis. In contrast, GH administration to healthy subjects caused a 21% increase in in vivo proteolysis (P = 0.0008). In vitro IGFBP-3 proteolysis was investigated by incubation of serum with 125I-rhIGFBP-3, followed by SDS-PAGE. In pretreatment samples, the percentage of proteolyzed 125I-rhIGFBP-3 was 13 +/- 1% (acromegalic subjects), 11 +/- 1% (healthy subjects), and 9 +/- 1% (GH-deficient subjects) (P < 0.009, GH-deficient vs. acromegalic subjects). Treatment had no effect on in vitro proteolysis. We conclude that GH status has no major impact on IGFBP-3 protease activity in serum.

Acromegaly↗

Immunephenotyping of T lymphocytes from patients after allogeneic bone marrow transplantation.

The relative distribution of T cell subsets as defined by MABs was analyzed in PBMCs from 56 patients with various hematologic diseases. The percentage of PBMCs expressing the CD5 antigen revealed normal values shortly after transplantation. In most patients lymphocytes expressing CD8 were found in high proportion and CD4 in a low percentage. This resulted in a low CD4/CD8 ratio compared with that of lymphocytes from normal controls. In the course of time, a trend toward normalization was observed for all parameters investigated, however the kinetics of the recovery showed a marked heterogeneity. Nevertheless, we found a statistical correlation between the CD4+ cell count and the PHA transformation response. This could however, not be shown in ConA and PWM stimulated proliferation. No other correlation was found between any lymphocyte phenotype, as defined by MABs, and proliferative responses in vitro.

Bone Marrow Transplantation↗

Fish consumption, n-3 fatty acids in cell membranes, and heart rate variability in survivors of myocardial infarction with left ventricular dysfunction.

To elucidate a possible antiarrhythmic effect of long-chained n-3 polyunsaturated fatty acids, heart rate variability was assessed in 52 patients with a previous myocardial infarction and left ventricular dysfunction. The content of n-3 polyunsaturated fatty acids in platelets was closely associated with the patient's fish-consuming habits, and a significant positive correlation was observed between the n-3 fatty acid docosahexaenoic acid and heart rate variability.

Aged↗

Blockade of the renin-angiotensin-aldosterone system prevents growth hormone-induced fluid retention in humans.

To test if the renin-angiotensin-aldosterone system (RAAS) is involved in growth hormone (GH)-associated fluid retention, we examined the effect of GH administration in the presence or absence of RAAS blockade at different levels on body fluid homeostasis. Eight subjects were examined in a controlled, randomized double-blinded trial. During four 6-day periods they received subcutaneous GH (6 IU-m-2) or placebo injections and tablets as follows: 1) placebo and placebo, 2) GH and placebo, 3) GH and captopril, and 4) GH and spironolactone. GH increased extracellular volume (liters; placebo 18.87 +/- 0.85; GH + placebo 20.43 +/- 1.01) but this effect was abolished by captopril (GH + captopril 18.82 +/- 0.67) and spironolactone (GH + spironolactone 18.99 +/- 0.85). Correspondingly, the GH-induced reduction in bioimpedance was blocked by captopril and spironolactone. Plasma renin and angiotensin II concentrations increased during all three GH treatment regimens, whereas plasma aldosterone was increased only after GH plus spironolactone. The data demonstrate that GH activates the RAAS and that blockade of the RAAS by two separate mechanisms prevents fluid retention normally encountered after GH exposure. These observations suggest that the RAAS plays a key role in GH-induced regulation of fluid homeostasis.

Adult↗

An external quality assessment study on the analysis of methylmalonic acid and total homocysteine in plasma.

In spite of the increasing interest in the analysis of methylmalonic acid and total homocysteine in plasma, data on interlaboratory variation is lacking. We report the results of an external quality assessment study with the participation of 15 laboratories in the Scandinavian countries performing these analyses on a regular basis. For methylmalonic acid, using serum, heparin fluoride plasma and an aqueous sample, CVs were found in the range of 11-17%. For total homocysteine using EDTA plasma, heparin fluoride plasma and an aqueous sample, CVs were in the range of 6-12%. For both analytes, a significant correlation between the individual recoveries of added analyte and the results for the aqueous sample was found, suggesting that the use of inconsistent calibrations in the participating laboratories are contributing to the interlaboratory variation. An acceptable range for results from the individual laboratory was calculated using data on the biological within-subject and between-subject variations reported in the literature. These ranges were violated by several laboratories when using the consensus mean or median as target values. Even if the results of the present study document a reasonable standard in the measurement of methylmalonic acid and total homocysteine in plasma in the participating laboratories there is room for improvement and a permanent scheme of external quality assessment using relevant samples is essential. From 1997, a regular scheme has been available from our laboratory.

Anticoagulants↗