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A van den Ende

Publications and source records attributed to A van den Ende.

At least 19 recordsLinked to original sources
PubMed1999

The 20210 G-->A mutation in the 3'-untranslated region of the prothrombin gene and the risk for arterial thrombotic disease.

A sequence variation in the 3'-untranslated region of the prothrombin (PT) gene (20210 G-->A) was recently claimed to be associated with elevated plasma prothrombin levels and an increased risk for venous and arterial thrombosis. We examined the prevalence of the 20210 A allele in the prothrombin gene in 400 healthy controls and in 263 patients with proven premature atherosclerotic disease. In addition, we measured prothrombin, prothrombin fragment 1 + 2, thrombin-antithrombin (TAT) complex and D-dimer levels in plasma from carrier and non-carrier patients. The frequency of the variant allele was 1% in the control subjects and 2.7% in the patient group, yielding a relative risk (RR) for the 20210 A allele of 2.7 (95% CI 0.8-9.4). All heterozygotes in the patient group were found to have had a myocardial infarction (MI), yielding a RR for MI of 4.2 (95% CI 1.2-14.6). Plasma prothrombin levels in carriers (126+/-10) were higher than in non-carriers (103+/-1, P=0.02). The levels of TAT complexes (16+/-9 v 6+/-1 microg/ml, P=0.02) as well as of prothrombin fragment 1 + 2 (1.5+/-0.3 v 1.0+/-0.1 nmol/l, P=0.02) were also elevated in carriers of the mutation. Our findings suggest that the 20210 G-->A mutation in the prothrombin gene is a genetic risk factor for MI. In addition, our data provide evidence for an association of the mutation with excessive thrombin generation, which may contribute to the understanding of its role in venous and arterial disease.

Adult↗
PubMed1998

Prevalence of hereditary haemochromatosis in premature atherosclerotic vascular disease.

It has been proposed that iron accumulation may contribute to atherogenesis by increasing free radical formation and oxidative stress. Epidemiological studies in which the association of iron status with atherosclerosis was assessed raised conflicting results. To test whether genetic haemochromatosis is associated with increased atherosclerosis, we determined the prevalence of two mutations in the HFE gene related to haemochromatosis (845G-->A; Cys282Tyr. and 187 C-->G, His63Asp) in 265 consecutive patients with premature (<50 years of age) angiographically-proven atherosclerotic disease (coronary and/or peripheral), and in 272 healthy controls. PCR amplification followed by RsaI (Cys282Tyr analysis) and BclI (His63Asp analysis) restriction digestion was employed to define the genotypes. The mutant Cys282Tyr allele had a frequency of 0.07 among controls and 0.04 among patients (carrier frequency of 14.0% and 8.3%, respectively). The frequency of the His63Asp mutant allele was 0.14 (28.6% of carriers) in controls and 0.11 (22.2% of carriers) in patients. Five of 265 patients (1.1%) and 9/272 controls (3.3%) were compound heterozygotes. In conclusion, a lower prevalence of the Cys 282Tyr mutation and a similar frequency of the His63Asp mutation was observed in patients with atherosclerotic disease in comparison with normal controls. These findings do not support an association between haemochromatosis and atherogenesis.

Adolescent↗
PubMed1997

Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia.

Interleukin-10 (IL-10) has been found to inhibit lipopolysaccharide (LPS)-induced tissue factor expression by monocytes in vitro. To determine the effects of IL-10 on LPS-induced activation of the hemostatic mechanisms in vivo, we performed a placebo-controlled, cross-over study of human endotoxemia. Two groups of eight volunteers were challenged with LPS (4 ng/kg) on two occasions: once in conjunction with placebo, and once with recombinant human IL-10 (rhIL-10; 25 microg/kg). In group 1, placebo or rhIL-10 was given 2 minutes before LPS challenge, group 2 received placebo or rhIL-10 1 hour after LPS administration. Pretreatment with rhIL-10 reduced both LPS-induced activation of the fibrinolytic system (plasma concentrations of tissue type plasminogen activator, plasmin-alpha2-antiplasmin complexes, and D-dimer), and inhibition of fibrinolysis (plasma levels of plasminogen activator inhibitor 1), whereas posttreatment only inhibited the latter response. Both IL-10 pre- and posttreatment attenuated activation of the coagulation system (plasma levels of prothrombin fragment F1 + 2 and thrombin-antithrombin complexes). These results indicate that rhIL-10, besides its well-described inhibitory effects on cytokine release, potently modulates the fibrinolytic system and inhibits the coagulant responses during endotoxemia.

Adult↗
PubMed1997

Magnesium pyridoxal-5'-phosphate glutamate, "A vitamin B6 derivative", does not affect lipoprotein levels in patients with familial hypercholesterolaemia.

OBJECTIVE: In this double-blind, randomized, placebo-controlled, dose-finding study we assessed the short-term efficacy and safety of increasing dosages of magnesium pyridoxal-5'-phosphate glutamate (MPPG) compared to placebo in patients with familial hypercholesterolaemia (FH). Twenty-three patients of either sex, over the age of 18 years and suffering from heterozygous FH, were treated with MPPG for a period of 16 weeks. RESULTS: Baseline characteristics and lipoprotein profiles of the patients were comparable in the two treatment groups. Overall compliance was 90%. Neither after the first 8 weeks treatment period with 450 mg MPPG daily nor after the second 8 weeks treatment period with 600 mg MPPG daily were statistically significant changes in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol or triglyceride levels observed between the treatment and placebo groups. Plasma levels of lipoprotein (Lp)(a), apolipoprotein (apo) A1, apo B100, very low density lipoprotein (VLDL) cholesterol and VLDL triglyceride also did not change. CONCLUSION: Although it has been demonstrated that MPPG improves lipoprotein levels in patients with different forms of dyslipidaemia, MPPG is not effective for the treatment of FH patients.

Adult↗
PubMed1997

A randomized cross-over study comparing pharmacodynamic and metabolic variables of a new combiphasic and a well-established triphasic oral contraceptive.

In an open-label, randomized, cross-over study in 20 subjects, the short-term effects were investigated of Gracial (DSG/EE 7 x 25/40 micrograms/day + 15 x 125/30 micrograms/day) and Trigynon (LNG/EE 6 x 50/30 micrograms/day + 5 x 75/40 micrograms/day + 10 x 125/30 micrograms/day) on plasma concentrations of 17 beta-estradiol and progesterone as well as on carrier proteins (SHBG, CBG, ceruloplasmin), AT-III, carbohydrate metabolism (insulin, glucose, glycosylated proteins) and lipid metabolism (total cholesterol, triglycerides, phospholipids, HDL-C, LDL-C, HDL2-C, HDL3-C, HDL2-C/HDL3-C ratio, Apo A1, Apo B, Apo A1/Apo B ratio). Both preparations adequately and similarly inhibited ovulation in all subjects. Serum levels of carrier proteins were significantly higher with DSG/EE than with LNG/EE, whereas no between-group differences were observed with respect to fasting glucose and insulin, glycosylated proteins (mainly glycosylated albumin) and AT-III activity. DSG/EE showed significantly higher plasma levels than LNG/EE of estrogen-dependent lipid parameters such as triglycerides, HDL-C, HDL2-C, Apo A1, HDL2-C/HDL3-C ratio and Apo A1/Apo B ratio, whereas the levels of LDL-C and Apo B were significantly lower. Both oral contraceptive preparations were equally effective in suppression of follicular development, but combiphasic DSG/EE induced higher plasma levels of carrier proteins and higher plasma levels of potentially anti-atherogenic lipid parameters than did triphasic LNG/EE.

Antithrombin III↗
PubMed1997

Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia.

High-density lipoproteins (HDL) can bind and neutralize lipopolysaccharides (LPS) in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation. In this study, the effects of reconstituted HDL (rHDL) on LPS-induced coagulation, fibrinolysis and platelet activation in humans were investigated. In a double-blind, randomized, placebo-controlled, cross-over study, eight healthy male volunteers were injected with LPS (4 ng/kg) on two occasions, once in conjunction with rHDL (40 mg/kg, given as a 4 h infusion starting 3.5 h prior to LPS injection), and once in conjunction with placebo. rHDL significantly reduced LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1 + 2) and fibrinolysis (plasma levels of tissue type plasminogen activator antigen, t-PA). No effect was observed on LPS-induced inhibition of the fibrinolytic pathway (PAI-1) or on the transient thrombocytopenia elicited by LPS. Furthermore, rHDL treatment significantly enhanced the inhibition of collagen-stimulated inhibition of platelet aggregation during endotoxemia, but had no such effect on arachidonate-stimulated platelet aggregation. rHDL treatment per se also reduced collagen-induced platelet aggregation. These results indicate that rHDL modifies the procoagulant state associated with endotoxemia.

Adult↗
PubMed1997

Effects of heparin therapy on fibrinolysis in patients with pulmonary embolism.

Previous investigations suggested that heparin administration to humans enhances the tissue type plasminogen activator (tPA) levels in blood, but it remains uncertain whether this effect induces fibrinolysis. We studied the effect of therapeutic levels of heparinization on plasma markers for fibrinolysis in patients suspected of pulmonary embolism (PE). Blood samples were taken from 49 consecutive patients; 28 had confirmed PE, 21 had PE excluded. On admission, the plasma levels of plasmin-alpha 2antiplasmin complexes and D-dimer were significantly higher in the patient group with PE compared to those in whom PE was excluded. After heparinization the tPA levels increased in both groups, showing that this effect was not dependent on the initial level of activity of fibrinolysis. In spite of this increment in tPA levels, the concentrations of plasmin-alpha 2antiplasmin complexes and D-dimer decreased. In conclusion, although heparinization in patients with or without pulmonary embolism does lead to elevated tPA:Ag levels, this is not accompanied by enhanced fibrinolysis.

Adult↗
PubMed1996

Lipoprotein [a].

Explore the source record for details and available documents.

Alleles↗
PubMed1996

Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia.

The safety, tolerability, and efficacy of a 12-wk treatment with pravastatin, 5, 10, and 20 mg/d, was evaluated in 72 children with heterozygous familial hypercholesterolemia (FH) in a double-blind, randomized and placebo-controlled study. The results show that pravastatin was well tolerated and that adverse events were mild and equally distributed among the three treatment groups. Plasma total and LDL cholesterol levels were significantly reduced in all pravastatin treatment groups, in comparison with the control group; -24.6% (-28.1 to 21.0) and -32.9% (-37.0 to -28.6), for mean change and 95% confidence interval, respectively. In four children plasma LDL cholesterol levels were reduced within normal limits for sex and age. HDL cholesterol increased in the pravastatin 20-mg group, +10.8% (+3.4 to +18.8), whereas plasma apo B100 and very LDL (VLDL) cholesterol levels were reduced within all pravastatin-treated groups -26.8% (-31.2 [corrected] to -21.7) and -24.5% (-35.0 to -12.3). These data show that short-term pravastatin treatment of children with FH is safe and effective, although long-term dose titration studies with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors need to be performed, to reduce plasma LDL cholesterol levels below a predefined level. The results of these studies have to be awaited before new treatment strategies are to be considered in these children.

Adolescent↗
PubMed1995

Experience in the long-term treatment of patients with hirsutism and/or acne with cyproterone acetate-containing preparations: efficacy, metabolic and endocrine effects.

The effects and side effects of long-term treatment with cyproterone acetate (CPA) are described. Hammerstein's reverse sequential regimen (10 days 100 mg CPA, 21 days 50 micrograms ethinylestradiol (EE)) was used in most cases, although postmenopausal and hysterectomized women received 50 mg CPA/day continuously as monotherapy. The degree of androgenization was assessed in 143 of a total group of 188 women treated from 1968 to the present. The results of the treatment were good or very good in about 75% of hirsutism patients and in more than 90% of acne patients. Adverse events were recorded in 23% of cases. Most were mild and transient, and caused discontinuation of the therapy in only 9% of patients. From this population representing all cases treated and analysed retrospectively, a subgroup of patients was selected for a prospective investigation. Thirty-five patients with good response to CPA and longlasting therapy were included into this 2-year follow-up study; of these, 24 had previously received CPA for 5 or more years, 9 for more than 10 years and 2 for more than 15 years. Treatment in these patients consisted of 5 different regimens of various doses of CPA combined with EE and CPA alone in order to evaluate possible effects of concomitant estrogen treatment as well as a possible dose- or time-dependency of potential side effects. Clinicochemical, metabolic and endocrine parameters were determined at the start and end of the study. The hematological and clinicochemical parameters were within the normal ranges. There was a slight decrease of glucose tolerance and a moderate increase of insulin and C peptide after oral glucose loading. The effects of CPA and EE on lipometabolism were slight and apparently dependent on the dose of CPA and the therapeutic regimen. No suppression of adrenal function or of responsiveness to ACTH was seen. Fasting prolactin levels and serum prolactin concentrations after provocation with metoclopramide did not show any gross deviations. Sonography of the breast and liver did not show any abnormalities apart from adenofibrosis or mastopathy in 2 patients. In conclusion, CPA with or without EE was in our hands an effective and safe method of long-term treatment of hirsutism and/or acne in women.

Acne Vulgaris↗
PubMed1994

Serum distribution of two contraceptive progestins: 3-ketodesogestrel and gestodene.

A cross-over study of two oral contraceptive formulations, containing 30 micrograms ethinylestradiol in combination with 150 micrograms desogestrel (Marvelon) or 75 micrograms gestodene (Femovan), has been performed to compare the serum distribution and pharmacokinetics of gestodene and the active metabolite of desogestrel, namely 3-ketodesogestrel. Serum concentrations of both sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) were also measured and were increased more than 3-fold and 2-fold, respectively, on day 21 of the treatment cycle, with no statistically significant difference between treatment groups. In addition, 35 days after ingestion of either oral contraceptive had ceased, the serum SHBG and CBG concentrations were similar to the pretreatment values. During treatment cycles, increased serum SHBG levels were associated with a redistribution of 3-ketodesogestrel and gestodene such that the non-protein-bound (NPB) and albumin-bound fractions were reduced in concert with an increase in the relative proportions bound to SHBG. The proportion of gestodene bound to SHBG was consistently higher than that observed for 3-ketodesogestrel, and this undoubtedly reflects the higher affinity of SHBG for gestodene (Kd = 1.2 nM at 37 degrees C) when compared to 3-ketodesogestrel (Kd = 4.7 nM at 37 degrees C). It also probably accounts, in part, for the much higher total serum levels of gestodene (8.58 nmol/L) when compared to 3-ketodesogestrel (2.37 nmol/L) during the treatment cycles. Consequently, the absolute amounts of NPB, non-SHBG-bound, and SHBG-bound gestodene are significantly higher than those measured for 3-ketodesogestrel. It is concluded that ethinylestradiol-induced increases in serum SHBG levels during treatment with Marvelon or Femovan, influenced the distribution and total amount of 3-ketodesogestrel and gestodene in serum, respectively, and that this, combined with the higher affinity of SHBG for gestodene, results in a greater amount of bioavailable gestodene compared to 3-ketodesogestrel, despite the smaller dose of gestodene administered.

Adult↗
PubMed1994

The effect of two regimens of hormone replacement therapy on the haemostatic profile in postmenopausal women.

The effect of two different regimens of hormone replacement therapy on coagulation and fibrinolysis was measured in 30 women taking Tibolone (Livial) and 30 taking oestradiol valerate, sequentially combined with cyproterone acetate (Climen). Blood samples were taken before the beginning of the medication, then six and twelve months afterwards. The Livial group showed a rise of fibrinolytic activity as measured by the alpha 2-antiplasmin-plasmin complexes. Tissue plasminogen activator antigen and plasminogen activator inhibitor-1 decreased simultaneously. No effect was seen in the coagulation variables. In the Climen group no significant alterations were noticed, either in the coagulation or in the fibrinolysis variables. In the direct comparison of both substances only factor VII appeared to be significantly higher in the Climen group after six months and one year of treatment.

Anabolic Agents↗
PubMed1990

Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer.

Lumbar bone mineral density (BMD) determination by dual photon absorptiometry was used to study the influence of adjuvant chemotherapy for premenopausal breast cancer on the risk of premature osteoporosis. Six cycles of combination chemotherapy caused ovarian failure in 31 of 44 (71%) women, amenorrhoea mostly already beginning during treatment. In contrast, only seven of 44 (16%) women, who were pair-matched for age and year of breast cancer surgery and had not been treated with chemotherapy, were post-menopausal at the time of measurement. The mean interval after breast surgery was 3.5 years. The significantly decreased BMD in the treated group (1.17 compared to 1.29 g cm-2) could only be explained by the high incidence of menopause in these women, which on average occurred 10 years prematurely. Extrapolation of these findings suggests that adjuvant chemotherapy may precipitate osteoporotic fractures by some 10 years in a considerable proportion of women cured of premenopausal breast cancer.

Adult↗
PubMed1989

Storage of whole blood for up to 24 hours at ambient temperature prior to component preparation.

The effect of rapid cooling to 20-24 degrees C of whole blood immediately after collection, using 'cooling units' with butane-1,4-diol and prolonged storage up to 24 h at ambient temperature was investigated in the whole blood and the subsequently prepared plasma, buffy coat and buffy-coat-poor red cell concentrate (BC-poor RCC) in saline-adenine-glucose-mannitol (SAG M) solution. Factor VIII:C content of the plasma (n = 10), after 24 h storage was 80 +/- 3% of the initial value. In routine procedures factor VIII:C content in the plasma (n = 129 pools of 20 donor units plasma) was 0.77 +/- 0.078 IU/ml, after storage of the whole blood for 16-20 h. In whole blood (n = 10), the 2,3-diphosphoglycerate (2,3-DPG) content of the red cells decreased from 4.36 +/- 0.55 to 1.47 +/- 0.6 mumol/ml red cells after 24 h storage at 20-24 degrees C. After storage of the BC-poor RCC (n = 10) at 2-6 degrees C for 1 week, the 2,3-DPG had dropped to 0.76 +/- 0.46 mumol/ml red cells. During the first 24 h of storage of whole blood, the adenine triphosphate (ATP) levels of the red cells remained stable. A mean increase of 20% of the initial value was observed after addition of SAG M solution. In the BC-poor RCC the ATP slowly decreased to 81 +/- 5% after 5 weeks and to 68 +/- 6.6% of the initial value after 6 weeks storage.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3-Diphosphoglycerate↗
PubMed1989

Storage of leukocyte-poor red cell concentrates: filtration in a closed system using a sterile connection device.

Storage of leukocyte-poor red cell concentrates (LP-RCC) was investigated after filtration in a closed system that was assembled using a Sterile Connection Device (SCD). The LP-RCC were stored for up to 6 weeks following filtration with either 0.9% saline solution (n = 14) or saline-adenine-glucose-mannitol (SAG M) solution (n = 15) to prime and rinse the cellulose acetate filter. The results were compared with the data of nonfiltered buffy-coat-poor red cell concentrates (BC-poor RCC) stored in SAG M solution (n = 10). All LP-RCC contained less than 10(6) leukocytes whereas the nonfiltered BC-poor RCC contained 675 +/- 286 X 10(6) leukocytes at day 1, decreasing to 83 +/- 49 x 10(6) at day 42. Although glucose consumption, lactic acid production and decrease in pH was similar from day 7 through 28 in both groups of LP-RCC, a significantly steeper decline of ATP values as well as a higher hemolysis and LDH release was observed in the LP-RCC filtered with saline. During storage of the nonfiltered BC-poor RCC in SAG M, significantly higher glucose consumption (p less than 0.01), LDH release (p less than 0.001), rate of hemolysis (p less than 0.001) and a lower pH (p less than 0.001) were found, compared to the filtered units. It is postulated that the leukocytes present in the nonfiltered BC-poor RCC were responsible for these differences. The ATP values in the SAG-M-filtered and nonfiltered BC-poor RCC in SAG M were comparable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine↗
PubMed1988

Preparation of leukocyte-poor platelet concentrates from buffy coats. III. Effect of leukocyte contamination on storage conditions.

To study the influence of contaminating leukocytes on the storage conditions of platelet concentrates (PC), various amounts of leukocytes were added to identical PC. From 12 blood donations, 12 leukocyte-poor PC were prepared and pooled. Subsequently, the pool was divided into 12 identical PC. The plasma volume of the PC was 58.6 +/- 0.6 ml, the platelet concentration was 1.01 +/- 0.04 x 10(9)/ml (mean +/- SD) and the red cell contamination did not exceed 10(7) per PC. To 4 groups of 3 PC, pooled leukocytes were added from the same 12 blood donations. The leukocyte contamination for each group of 3 PC was 0.14 +/- 0.05, 1.96 +/- 0.09, 5.53 +/- 0.98 and 13.0 +/- 0.93 x 10(6)/ml (mean +/- SD) for groups I-IV, respectively. The PC were stored for 7 days at 22 degrees C in normal polyvinylchloride bags. A significant correlation was found between increasing concentrations of leukocytes in the PC and the drop in pH (r = -0.93), glucose consumption (r = -0.91), lactic acid production (r = 0.93) and release of lactate dehydrogenase (r = 0.92) during storage of the PC. The excretion of beta-thromboglobulin, depletion of platelet adenine nucleotides, decreased ability to incorporate 3H-adenosine into metabolic nucleotides and poor morphology of the platelets were also significantly correlated with an increased number of leukocytes in the PC. These data show that high concentrations of leukocytes in PC have a significant detrimental effect on the viability of platelets during storage at 22 degrees C. We conclude that for good storage conditions of PC, the upper limit of leukocytes per PC should not exceed 10(7).

Blood Platelets↗
PubMed1987

Determination of urinary cystine for monitoring anticystinuric therapy.

Cystine is assayed in urine by a method adapted from the procedure of Haux and Natelson (Clin Chem 1970;16:366-369) and modifications of the method, which improved its specificity, are presented. Assay imprecision (CV) at four different cystine concentrations (range: 0.042-1.658 mmol/l) varied from 23.1% to 3.7%. Analytical recovery was 94.6 +/- 6.0%. D-Penicillamine, alpha-mercaptopropionylglycine, L-glutamine and metabolites, added to urine, had negligible effect on the results of the cystine assay. Samples were stable for 3 wk when stored at 4 degrees C or frozen. Cystine excretion (mmol/24 h) in apparently healthy persons ranged from 0.041 to 0.170 (mean +/- SD: 0.099 +/- 0.039). Cystine excretions are presented in patients treated with anticystinuric drugs.

Amino Acids↗