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J Lindemans

Publications and source records attributed to J Lindemans.

At least 37 records · Page 2Linked to original sources
PubMed1999

Optimization of apolipoprotein(a) genotyping with pulsed field gel electrophoresis.

BACKGROUND: Increased lipoprotein(a) is a risk factor for atherosclerosis, and its concentration in serum is inversely correlated with the size of the apoliprotein(a) [apo(a)] component. The size of the apo(a) gene is determined mainly by the Kringle IV size polymorphism. We have optimized and characterized pulsed field gel electrophoresis (PFGE) for apo(a) genotyping. METHODS: Established PFGE protocols were adjusted. The changes included the following: (a) increased DNA yields by the use of all leukocytes for isolation from either 3 mL of fresh EDTA whole blood or 250 microL of frozen buffy coats; (b) increased efficiency of Kpn1 digestion by the inclusion of a digestion buffer wash; (c) reduction of assay time by the use of capillary blotting; (d) increased sensitivity by the use of four digoxigenin-labeled apo(a) probes; and (e) identification using a single film by the inclusion of a digoxigenin-labeled lambda marker probe in addition to apo(a) probes in the hybridization mix. RESULTS: In older Caucasians, 93% (buffy coats, n=468) were heterozygous for apo(a) gene size. An inverse correlation between serum lipoprotein(a) and the sum of Kringle IV alleles was found (y = -23x + 1553; r = -0.442; n = 468). Gel-to-gel variation was minimal (3%). Imprecision (SD) was one Kringle IV repeat (control sample containing eight fragments of 72-233 kb; n=34 electrophoretic runs). CONCLUSIONS: The practicality and sensitivity of the apo(a) genotyping technique by PFGE were improved, and accuracy and reproducibility were preserved. The optimized procedure is promising for apo(a) genotyping on frozen buffy coats from large epidemiological studies.

Alleles↗
PubMed1999

Serum caeruloplasmin as a coronary risk factor in the elderly: the Rotterdam Study.

Serum Cu and caeruloplasmin levels have been suggested to be independent risk factors for CHD operating through oxidative modification of LDL. However, given its function as an acute-phase protein, the question has been raised whether an elevated caeruloplasmin level is not merely an indicator of inflammation. In the current study, we investigated whether serum caeruloplasmin was associated with subsequent myocardial infarction, taking into account indices of inflammation. The study population consisted of 210 cases of first myocardial infarction and controls, frequency-matched on age (5-year categories) and sex, selected from the population-based cohort of the Rotterdam Study. Serum caeruloplasmin levels were significantly elevated in cases of myocardial infarction compared with controls (510 (SD 110) v. 470 (SD 100) mg/l; P = 0.007). Risk of myocardial infarction for the highest compared with the lowest quartile of caeruloplasmin was 2.46 (95% CI 1.04, 6.00; Ptrend = 0.043) after adjustment for age, sex, BMI, pack-years smoked, serum cholesterol, systolic blood pressure, and income. The relative risk was most evident in current smokers. Adjustment for C-reactive protein and leucocyte count reduced the excess risk by 33%. This suggests that a substantial part of the observed association between serum caeruloplasmin and CHD may be attributed to inflammation processes rather than to the pro-oxidant activity of caeruloplasmin.

Aged↗
PubMed1999

Portable blood gas and electrolyte analyzer evaluated in a multiinstitutional study.

A recently introduced blood gas/electrolyte analyzer (SenDx 100((R)), renamed ABL70) intended for point-of-care, near-patient, or stat laboratory use was evaluated simultaneously in four different institutions and compared with three different laboratory bench analyzers with respect to imprecision, inaccuracy (assessed by tonometry), and patient-sample analyses. The analyzer is equipped with a sensor cassette and a reagent cartridge for 50, 100, or 200 analyses and 100 or more traditional quality-control measurements. One analysis requires 170 microL of whole blood and takes <90 s. Statistically, the instrument performed somewhat better (lower CVs) for PO2 and potassium and somewhat worse for pH, PCO2, and ionized calcium than the respective comparison analyzers. However, the overall performance (in terms of CV and accuracy) was satisfactory in terms of clinical (e.g., CLIA '88) goals in all institutions. The mean difference and the CV of that difference in some 400 patient-sample comparisons were as follows: 0.010 (+/- 0.002%) for pH, -0.65 mmHg (+/- 4%) for PCO2, -0.49 mmHg (+/- 6%) for Po2, 0.44 mmol/L (+/- 1.2%) for sodium, -0.013 mmol/L (+/- 2.9%) for potassium, -0.016 mmol/L (+/- 2.6%) for ionized calcium, and -0.016 L/L (+/- 7. 1%) for the hematocrit. Its acceptable analytical performance and ease of operation make the SenDx 100 suitable for the analysis of blood gases and electrolytes.

Blood Chemical Analysis↗
PubMed1998

Combined use of erythrocyte zinc protoporphyrin and mean corpuscular volume in differentiation of thalassemia from iron deficiency anemia.

In a retrospective study the diagnostic value of erythrocyte zinc protoporphyrin (ZPP) measurement as a means of distinguishing iron deficiency anemia from thalassemia syndromes in patients with microcytosis was explored. ZPP values were increased in all patients with iron deficiency and in part of the patients with thalassemia. The combined measurement of erythrocyte mean corpuscular volume (MCV) and ZPP resulted in a correct classification of patients with iron deficiency and with thalassemia in more than 95%. The predictive value of this method is better than the results obtained by using formulae derived from red cell indices. In population screening programs for thalassemia syndromes, in which MCV determination is used as the initial test, the ZPP test is recommended as a second test, in order to discriminate between patients with microcytosis due to iron deficiency and patients with microcytosis due to thalassemia syndromes.

Adult↗
PubMed1998

Zinc protoporphyrin as screening test in female blood donors.

Erythrocyte zinc protoporphyrin (ZPP) was measured in 102 women blood donors to evaluate its usefulness in screening for evolving iron deficiency anemia, a reason for the deferral of donors. The results were compared with serum ferritin determinations. Five women were deferred before their first donation and eight women were deferred after one or two donations. Women with increased ZPP values all had low serum ferritin concentrations, indicating iron-deficient erythropoiesis that was caused by iron depletion. The positive predictive value of an increased ZPP in predicting deferral of the donor after one or two donations was 75%, whereas a serum ferritin concentration < or = 12 microg/L predicted deferral in 26% of the donors. The results indicate that the ZPP test can be recommended as a feasible and inexpensive predonation test to determine a subset of donors with iron-deficient erythropoiesis at risk of developing iron deficiency anemia.

Adult↗
PubMed1997

Modulation of lipoprotein(a) atherogenicity by high density lipoprotein cholesterol levels in middle-aged men with symptomatic coronary artery disease and normal to moderately elevated serum cholesterol. Regression Growth Evaluation Statin Study (REGRESS) Study Group.

OBJECTIVES: This study sought to examine whether lipoprotein(a) levels predict coronary artery lumen changes in patients with symptomatic coronary artery disease (CAD) and normal to moderate hypercholesterolemia. BACKGROUND: Recent conflicting reports have confirmed or refuted the association of lipoprotein(a) with clinical events or angiographically verified disease progression. METHODS: The association between serum lipoprotein(a) and changes in coronary artery lumen was studied in 704 men entered into the Regression Growth Evaluation Statin Study (REGRESS), a double-blind, placebo-controlled, quantitative angiographic study that assessed the effect of 2 years of pravastatin treatment. The primary end points were changes in average mean segment diameter (MSD) and average minimal obstruction diameter (MOD). Pravastatin- and placebo-treated patients were classified as having progressing, regressing or stable CAD, and median lipoprotein(a) concentrations were compared. Bivariate and multivariate regression analyses were performed in the overall patient group and in high risk subgroups. RESULTS: Pravastatin treatment did not affect serum apolipoprotein(a) levels. Median in-trial (sampled at 24 months) apolipoprotein(a) levels for regressing, stable and progressing CAD were, respectively, 130, 162 and 251 U/liter in placebo-treated patients and 143, 224 and 306 U/liter in pravastatin-treated patients. Predictors of MSD and MOD changes were baseline MSD and MOD, in-trial apolipoprotein(a), in-trial high density lipoprotein (HDL) cholesterol and baseline use of long-acting nitrates. The multivariate models predicted 14% of MSD changes and 12% of MOD changes; apolipoprotein(a) predicted only 2.6% and 4.8%, respectively. However, in patients with in-trial HDL cholesterol levels <0.7 mmol/liter, apolipoprotein(a) predicted up to 37% of the arteriographic changes. CONCLUSIONS: Serum lipoprotein(a) levels predict coronary artery lumen changes in normal to moderately hypercholesterolemic white men with CAD; its atherogenicity is marked in the presence of concomitant hypoalphalipoproteinemia.

Anticholesteremic Agents↗
PubMed1997

Thermolabile methylenetetrahydrofolate reductase in coronary artery disease.

BACKGROUND: Hyperhomocysteinemia, an independent and graded risk factor for coronary artery disease (CAD), may result from both environmental and hereditary factors. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of methylenetetrahydrofolate to methyltetrahydrofolate, the methyl donor in the remethylation of homocysteine to methionine. A 677C-->T mutation in the MTHFR gene has been associated with elevated homocysteine concentrations in homozygous (+/+) individuals. METHODS AND RESULTS: We assessed the frequency of this common mutation in 735 CAD patients from the Regression Growth Evaluation Statin Study (REGRESS), a lipid-lowering coronary-regression trial, and in 1250 population-based control subjects. Furthermore, the association between the mutation and serum homocysteine concentrations was studied. The frequency of the homozygous (+/+) mutation was 9.5% among patients versus 8.5% among control subjects, resulting in an odds ratio of 1.21 (95% confidence interval [CI], 0.87 to 1.68), relative to the (-/-) genotype. Homocysteine concentrations were significantly elevated in both (+/+) and (+/-) individuals compared with (-/-) individuals (median homocysteine levels, 15.4, 13.4, and 12.6 micromol/L, for (+/+), (+/-), and (-/-) individuals, respectively). For a summary estimation of the risk of the (+/+) genotype for CAD, we performed a meta-analysis on 8 different case-control studies on thermolabile MTHFR in CAD. In the meta-analysis, the homozygous (+/+) genotype was present in 299 of 2476 patients (12.1%) and in 257 (10.4%) of 2481 control subjects, resulting in a significant odds ratio of 1.22 (95% CI, 1.01 to 1.47) relative to the (-/-) genotype. CONCLUSIONS: Both the homozygous (+/+) and heterozygous (+/-) genotype result in elevated homocysteine concentrations. From our meta-analysis, we conclude that the homozygous (+/+) genotype is a modest but significant risk factor for CAD.

Coronary Disease↗
PubMed1997

Methionine synthase deficiency without megaloblastic anaemia.

UNLABELLED: We report findings on a child presenting with neonatal homocystinuria, hypomethioninaemia and severe neurological symptoms, including developmental delay and seizures. Methylmalonic aciduria was not present. The activity of methionine synthase in fibroblasts was severely deficient and formation of methylcobalamin from 57Co labelled cyanocobalamin was very low. The patients cells complemented with those of a cblE patient but not with those of two cblG patients. No biochemical or clinical response to injections of hydroxycobalamin was found. Both off treatment and on betaine and methionine supplementation the patient, at age 8 years, has not developed megaloblastic anaemia. In addition, the patient is homozygous for the C677T polymorphism in the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene and the concomitant existence of this mutation with the methionine synthase defect may prevent folate < > and thus anaemia. CONCLUSION: We report the lack of megaloblastic anaemia in a patient with severe methionine synthase deficiency who is also homozygous for C677T in MTHFR, hypothesize that the MTHFR polymorphism protects the patient against anaemia and speculate that homozygosity for MTHFR C677T could cause the dissociation between haematological and neurological disease seen in some patients with vitamin B12 deficiency.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1997

A computer program for constructing multivariate reference models.

From a statistical point of view the simultaneous interpretation of multiple variables should be performed with a multivariate reference model rather than with multiple univariate reference intervals. A computer program for constructing and testing multivariate reference models is described. The use of the computer program is illustrated with a data set of total serum calcium concentrations and serum albumin concentrations from 222 2nd year medical students. Using a single univariate reference interval for total serum calcium, 17 students were classified as having an abnormal calcemic status while using a bivariate reference model for total serum calcium and serum albumin, 13 of these 17 students had in fact normal total serum calcium concentrations, taking into account their serum albumin concentrations.

Biometry↗
PubMed1997

Serum LP(a) levels in African aboriginal Pygmies and Bantus, compared with Caucasian and Asian population samples.

Serum lipoprotein(a) (Lp(a)) and its correlates were studied in African Aboriginal Pygmies (n = 146) and Bantus (n = 208) from Cameroon. Geometric mean Lp(a) levels were 274 and 289 mg/l in Bantu males and females, respectively, and 220 and 299 mg/l in Pygmy males and females, the gender difference being significant in Pygmies (p = 0.024). In Pygmies 41% and 52% of the males and females, respectively, had Lp(a) levels above 300 mg/l, compared with 47% and 55% in Bantus. Overall, Lp(a) levels did not significantly differ between Pygmies and Bantus, and did not correlate with age, body mass index (BMI), systolic and diastolic blood pressure. Compared with healthy Asian and Caucasian population samples, age- and BMI-adjusted geometric Lp(a) means were 2.3- to 5.0-fold higher in Pygmy and Bantu males, and 2.9- to 3.6-fold higher in Pygmy and Bantu females (p < or = 0.05). Across the population samples studied ethnicity predicted 12% and 17% of serum Lp(a) variance in males and females, respectively.

Adult↗
PubMed1997

Folate-responsive homocystinuria and megaloblastic anaemia in a female patient with functional methionine synthase deficiency (cblE disease).

This first detailed report of a female patient with functional methionine synthase deficiency due to the cblE defect describes treatment with several vitamins and cofactors and clinical progress for 17 years. Before treatment, major findings were microcephaly, psychomotor retardation, episodic reduced consciousness, megaloblastic anaemia, increased plasma free homocystine (> 20 mumol/L), low plasma methionine (< 10 mumol/L) and increased excretion of formiminoglutamate. On high-dose folic acid, biochemical abnormalities such as formiminoglutamate excretion and homocystinuria nearly normalized, but clinical and haematological abnormalities remained. On replacement of folate with methylcobalamin, alertness, motor function, speech and the electroencephalogram improved, biochemical features were similar, but the mean corpuscular volume increased. The best control was observed on a combination of folate and methylcobalamin. At 17 years of age she remains severely mentally retarded. In cultured fibroblasts methionine synthesis was reduced (0.03 nmol/mg/per 16 h, controls 2.4-6.9); methionine synthase activity was normal under high reducing conditions but decreased on limiting the reducing agent, dithiothreitol, to 5 mmol/L (18% of total, controls 51-81%); formation of methylcobalamin was low (4.5% of total cobalamins, control 57.5%) and complementation studies indicated the cblE defect. Methionine formation showed only minor increases in cells grown in folate- or cobalamin-supplemented medium. Serine synthesis, which was low in normal medium, increased with cobalamin supplementation. These studies suggest further heterogeneity within cblE mutants, show the difficulty of establishing the enzyme defect in vitro, and indicate a role for folate in addition to cobalamin in treatment.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed1997

Homocysteine, atherosclerosis and prevalent cardiovascular disease in the elderly: The Rotterdam Study.

OBJECTIVES: Elevated homocysteine increases the risk of vascular disease, in particular amongst younger subjects (< 60 years). Very few studies have been performed amongst older subjects. We evaluated the relation of plasma total homocysteine (tHcy) to atherosclerosis and symptomatic cardiovascular disease amongst older men and women. DESIGN: A cross-sectional study. SETTING: General population. SUBJECTS: A random sample of 630 men and women, participating in the Rotterdam Study, a prospective population-based cohort study amongst 7983 subjects aged 55 years and over residing in the Ommoord district of Rotterdam, the Netherlands. MAIN OUTCOME MEASURES: Carotid atherosclerosis (carotid plaques and common carotid intima-media thickness) assessed by ultrasonography; lower extremity (peripheral) artery atherosclerosis measured by the ratio of the ankle to arm systolic blood pressure; prevalent cardiovascular disease assessed as a history of myocardial infarction or stroke. RESULTS: Subjects, 55-74 years of age, with elevated tHcy levels (+/- 18.6 mumol L-1) had a thicker common carotid intima-media (difference 0.037 mm; 95% CI 0.001, 0.073), a lower ankle-arm index (-0.054; -0.104, -0.004), and an increased risk of cardiovascular disease (odds ratio 3.0; 1.5, 6.1), after adjusting for sex and age. There was no appreciable association of tHcy levels to atherosclerosis and cardiovascular disease in subjects aged 75 years and older. CONCLUSIONS: In subjects aged 55-74 years elevated tHcy is associated with an increased risk of atherosclerosis and cardiovascular disease. The lack of association in those aged > or = 75 years most probably reflect selective mortality.

Aged↗
PubMed1997

Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones.

Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use.

Adult↗
PubMed1997

Significance of various parameters derived from biological variability of lipoprotein(a), homocysteine, cysteine, and total antioxidant status.

Analytical and biological components of variability and various derived indices have been determined for lipoprotein(a) [Lp(a)], homocysteine (Hcy), cysteine (Cys), and total antioxidant status (TAOS) in ostensibly healthy adult Caucasians and in stable outpatients with an increased serum Lp(a). In healthy Caucasians, average intraindividual biological CVs (CVb) were 20.0% for Lp(a), 9.4% for Hcy, 5.9% for Cys, and 2.8% for TAOS, CVbs being similar in men and women. In the outpatient group, CVbs were comparable for Hcy, Cys, and TAOS, but significantly lower for Lp(a) (7.5% vs 20.0%; P <0.0001). Moreover, a significant inverse relation between both biological and analytical CVs (CVa) and serum Lp(a) concentrations was demonstrated. We conclude that average CVa and CVb values, and hence average derived indices, are adequate for Hcy, Cys, and TAOS, whereas individual values should be used for Lp(a).

Adult↗
PubMed1996

Erythromelalgic, thrombotic and hemorrhagic manifestations in 50 cases of thrombocythemia.

Fifty consecutive patients with thrombocythemia (35 men and 15 women) were diagnosed as primary thrombocythemia (PT) in 30 and thrombocythemia associated with polycythemia vera (PV) in 20. The symptoms were platelet-mediated erythromelalgia in 16 PT and 15 PV, coronary artery disease in 3 PT and 2 PV, atypical cerebral ischemic attacks in 8 PT and 3 PV, paradoxical thrombosis and bleeding in 3 PT and 2 PV and hemorrhages alone in 6 PT and 2 PV patients. Erythromelalgia was localized in the forefoot sole and toes in 28, the fingertips in 9, the handpalm in 2. Untreated erythromelalgia progressed to acrocyanosis or peripheral ischemia with necrosis in a toe or fingertip in 14 cases. Painful red, warm and indurated erythromelalgic hot spots in the skin of the upper legs were misdiagnosed as superficial thrombophelebitis in 5 PT and 2 PV patients. Erythromelalgia in thrombocythemia already occurred at slightly increased platelet counts above 400 x 10(9)/l. The curative effect of aspirin on erythromelalgia in thrombocythemia was consistently accompanied by a significant increase of platelet counts. Erythromelalgia and bleeding paradoxically occurred in 5 patients at platelet counts between 1000 and 2000 x 10(9)/l. In this situation aspirin prevents erythromelalgic and microcirculatory circulation disturbances, but further increases the risk of serious bleeding complications. Presenting hemorrhagic manifestations in thrombocythemia were observed at platelet counts in excess of 1000 x 10(9)/l in 9 PT and 4 PV patients as severe epistaxis in 5, atypical ecchymoses in 3, gastrointestinal bleeding in 2 and secondary bleeding in 3. The concept of platelet-mediated erythromelalgia, thrombosis and hemorrhages in thrombocythemia is discussed.

Adult↗
PubMed1996

Phenotyping and genotyping of coagulation factor V Leiden.

The currently used activated Protein C resistance test demonstrated to be of limited diagnostic value for the detection of the mutant Factor V Leiden. Moreover, this assay is not useful for patients under anticoagulant therapy. A modification of the APC resistance test, applying Factor V deficient plasma is described which demonstrates a specificity and sensitivity of 1.0. The superiority of the modified APC resistance test over the existing APC resistance test was verified by genotyping. For that purpose, the Amplification Refractory Mutation System (ARMS) was applied to the detection of the G to A mutation at position 1691 in the gene encoding coagulation Factor V. The mutation at that position could be easily detected by using each of two allele-specific oligonucleotide primers concomitantly with one common primer in two separate polymerase chain reactions, thereby amplifying a fragment of 186 base-pairs of the Factor V gene.

Base Sequence↗
PubMed1995

Design and representation of multivariate patient-based reference regions for arterial pH, PCO2 and base excess values.

OBJECTIVES: To determine and compare the shape and location of three data sets of arterial pH, PCO2, and BE values from intensive care patients in a new acid-base chart for the purpose of deriving multivariate reference regions. DESIGN AND METHODS: The new chart is constructed by applying a statistical technique called principal component analysis (PCA). Three different data sets, each comprised of 1500 arterial pH, PCO2, and BE values, were subjected to PCA. The 3 data sets were collected in a respiratory intensive care unit (ICU) of a University Hospital, in a general ICU of a District Hospital, and in a neonatal ICU of a Children's Hospital. RESULTS: The outlines of the resulting charts are similar for all 3 data sets, but the representations of the three distributions in the new chart are highly dissimilar, both in shape and in location. CONCLUSIONS: PCA can be used to derive a patient-based reference region for arterial pH, PCO2, and BE values. Furthermore, the new chart may be useful for the graphical monitoring of acid-base data because distances between consecutive observations are faithfully represented.

Acid-Base Imbalance↗