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Biomedical subjects

M Jansen

Publications and source records attributed to M Jansen.

At least 37 records · Page 2Linked to original sources
PubMed2001

STK11/LKB1 Peutz-Jeghers gene inactivation in intraductal papillary-mucinous neoplasms of the pancreas.

Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of the STK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as well as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1 gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of the STK11/LKB1 gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1 gene. These results suggest that the STK11/LKB1 gene is involved in the pathogenesis of some IPMNs.

AMP-Activated Protein Kinase Kinases↗
PubMed2001

Atorvastatin improves blood rheology in patients with familial hypercholesterolemia (FH) on long-term LDL apheresis treatment.

To determine the effect of atorvastatin on blood rheology in patients with familial hypercholesterolemia (FH) on regular LDL apheresis, we prospectively studied the rheological variables fibrinogen, plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit and platelet aggregation in 12 patients (two homozygous, ten heterozygous) before and during treatment with atorvastatin. Baseline values of red cell aggregation and whole blood viscosity were increased in FH patients on regular LDL apheresis compared with healthy controls (P<0.05), whereas fibrinogen, plasma viscosity and hematocrit were similar in the two groups. Treatment with atorvastatin reduced red cell aggregation (P<0.01), whole blood viscosity (P<0.01), plasma viscosity (P<0.01) and platelet aggregation (P<0.05), but caused a slight increase in plasma fibrinogen (by 5%; P<0.01). Our findings suggest that atorvastatin improves blood rheology in patients with FH on regular LDL-apheresis. This improvement in blood flow properties may contribute to the well-known beneficial effects of atorvastatin on cardiovascular risk in patients with severe hyperlipidemia and atherosclerotic vascular disease.

Adult↗
PubMed2001

Protection of hematopoietic cells from O(6)-alkylation damage by O(6)-methylguanine DNA methyltransferase gene transfer: studies with different O(6)-alkylating agents and retroviral backbones.

Overexpression of O(6)-methylguanine DNA methyltransferase (MGMT) can protect hematopoietic cells from O(6)-alkylation damage. To identify possible clinical applications of this technology we compared the effect of MGMT gene transfer on the hematotoxicity induced by different O(6)-alkylating agents in clinical use: the chloroethylnitrosoureas ACNU, BCNU, CCNU and the tetrazine derivative temozolomide. In addition, various retroviral vectors expressing the MGMT-cDNA were investigated to identify optimal viral backbones for hematoprotection by MGMT expression. Protection from ACNU, BCNU, CCNU or temozolomide toxicity was evaluated utilizing a Moloney murine leukemia virus-based retroviral vector (N2/Zip-PGK-MGMT) to transduce primary murine bone marrow cells. Increased resistance in murine colony-forming units (CFU) was demonstrated for all four drugs. In comparison to mock-transduced controls, after transduction with N2/Zip-PGK-MGMT the IC50 for CFU increased on average 4.7-fold for ACNU, 2.5-fold for BCNU, 6.3-fold for CCNU and 1.5-fold for temozolomide. To study the effect of the retroviral backbone on hematoprotection various vectors expressing the human MGMT-cDNA from a murine embryonic sarcoma virus LTR (MSCV-MGMT) or a hybrid spleen focus-forming/murine embryonic sarcoma virus LTR (SF1-MGMT) were compared with the N2/Zip-PGK-MGMT vector. While all vectors increased resistance of transduced human CFU to ACNU, the SF1-MGMT construct was most efficient especially at high ACNU concentrations (8-12 microg/ml). Similar results were obtained for protection of murine high-proliferative-potential colony-forming cells. These data may help to optimize treatment design and retroviral constructs in future clinical studies aiming at hematoprotection by MGMT gene transfer.

Alkylating Agents↗
PubMed2001

Treatment of coagulation inhibitors with extracorporeal immunoadsorption (Ig-Therasorb).

Coagulation inhibitors may occur as alloantibodies in patients with congenital factor deficiencies or as autoantibodies in patients with a previously normal coagulation. We treated 10 patients with factor VIII inhibitors (three haemophiliacs and seven patients with acquired factor VIII inhibitors) and one patient with a factor V inhibitor using extracorporeal immunoadsorption to immobilized antibodies against human immunoglobulins (Ig-Therasorb). The initial inhibitor titre was between 18 BU/ml and 540 BU/ml. Nine patients had signs of bleeding. Eighty-nine immunoadsorption sessions were performed in the 11 patients (8.1 +/- 5.1 per patient), each processing 6980 +/- 880 ml of plasma in 3.8 +/- 0.5 h. The mean reduction of the inhibitor titre was 71.9 +/- 19.4% per session. Serum IgG, IgA and IgM levels decreased by 68.7 +/- 10.1%, 55.7 +/- 12.7% and 48.6 +/- 11.1% respectively. In two haemophiliac patients, an initial titre reduction prior to an immune tolerance protocol was performed. Another haemophiliac patient was treated because of acute cerebral bleeding. In six out of eight patients with acquired inhibitors, a durable elimination was achieved within a median of 18 d. Treatment was safe and well-tolerated and seems to be a promising method in the treatment of patients with coagulation inhibitors, especially when a fast inhibitor titre reduction is necessary.

Adult↗
PubMed2001

Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age.

OBJECTIVE: To assess possible side-effects of long-term continuous growth hormone (GH) treatment on carbohydrate (CH) metabolism in children with short stature born small for gestational age. DESIGN: In a prospective, randomised double-blind, dose-response multicentre trial, the effect of GH treatment on CH metabolism was evaluated, comparing two GH dosages [3 vs. 6 IU/(m(2) body surface.day)]. PATIENTS: Seventy-eight children with short stature (height SD-score < - 1.88) born small for gestational age (birth length SD-score < - 1.88) being all prepubertal with a mean (SD) chronological age of 7.3 (2.2) years before start of treatment. MEASUREMENTS: Glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) and glycosylated haemoglobin (HbA(1c)) were measured before and during 6 years of GH treatment. RESULTS: Before treatment, the glucose response to oral glucose after 120 min was in six of the 78 children (8%) above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance (IGT), whereas after 6 years of GH treatment, IGT was found in 4% of the children. None of the children developed diabetes mellitus. Mean fasting glucose levels had increased significantly by 0.5 mmol/l after 1 year of GH treatment, without a further increase thereafter. The 2-h area under the curve adjusted for fasting levels (AUCab) for glucose and the HbA(1c) levels were lower after 6 years of GH treatment compared to baseline. During GH treatment, all HbA(1c) levels were in the normal range. In contrast to the effects on glucose levels, GH treatment induced considerably higher fasting insulin levels and glucose-stimulated insulin levels. The increase in AUCab for insulin occurred particularly during the first year of treatment, whereas the fasting insulin levels showed a further increase from one to six years. As a result, the 30- and 120-min ratios of insulin to glucose were higher during GH treatment compared to the start of treatment. The children who remained prepubertal during the entire study period showed similar patterns in glucose and insulin levels compared to the children who entered puberty. None of the observed changes were different between the GH dosage groups. CONCLUSIONS: Continuous GH treatment during 6 years in children with short stature born small for gestational age has no adverse effects on glucose levels, even with dosages up to 6 IU/(m(2) d). However, as has been reported in other patient groups, GH treatment induces higher fasting insulin levels and glucose-stimulated insulin levels, indicating relative insulin resistance. Since the consequences of long-term hyperinsulinism during childhood are unknown, careful follow-up of these GH-treated children born small for gestational age is required.

Area Under Curve↗
PubMed2001

Long-term follow-up of percutaneous transhepatic therapy (PTT) in patients with definite benign anastomotic strictures after hepaticojejunostomy.

BACKGROUND AND STUDY AIMS: Percutaneous transhepatic therapy (PTT) is a promising minimally invasive procedure for benign stenosis of the anastomosis after hepaticojejunostomy. In this prospective study, the effectiveness and safety of this technique were investigated. PATIENTS AND METHODS: Between October 1995 and May 2000 34 consecutive patients were referred for treatment of symptomatic cholestasis due to anastomotic strictures after hepaticojejunostomy. In all patients percutaneous transhepatic cholangioscopic (PTCS) drainage and bougienage of the stenosis up to 16 Fr were performed. Associated bile duct stones were fractured using PTCS laser lithotripsy and removed into the jejunum. Afterwards, patients received transhepatic drainage for 3 months initially. The tubes were replaced in case of persistent strictures every 3 months up to 1 year. Patients in whom treatment failed underwent surgery or received biliary metal stents, depending on risk factors and individual anatomy. RESULTS: The procedure was performed in 34 patients (mean age 57 +/- 15) with cholestasis (alkaline phosphatase 691 +/- 485 U/l, bilirubin level mean 3.2 +/- 3.1 mg/dl). The transhepatic tube was successfully positioned into the right hepatic bile duct (n = 25), into the left (n = 3), or into both (n = 3) after 4 +/- 1 sessions, except in two patients in whom an external drainage was used and another patient in whom the procedure had to be stopped due to a bleeding complication. In 14 patients bile duct stones were successfully treated by PTCS laser lithotripsy before the placement of a transhepatic tube. The 30-day morbidity and mortality rates were 23.5% and 0% respectively. In 23 patients, the transhepatic tube could be removed after 212 +/- 122 days, with no evidence of cholestasis during a further follow-up of 736 +/- 479 days. Four patients received metal stents because of persistent strictures after transhepatic intubation. Surgery had to be performed in a total of five patients, because of recurrent bile duct stones or recurrent strictures, in one patient with previous implantation of a metal stent, and in two patients with bile duct disconnection. Two patients died, one 1.5 years after surgery and one 427 days after metal stent implantation. None of these cases was related to the procedure. In two patients, the transhepatic tube is still in situ. CONCLUSIONS: Percutaneous transhepatic treatment of anastomotic strictures after hepaticojejunostomy is safe and highly effective in achieving internal biliary drainage. Temporary transhepatic intubation seems to be a promising minimally invasive alternative to surgery.

Adult↗
PubMed2001

Modulation of the cytochrome P450-mediated metabolism of ifosfamide by ketoconazole and rifampin.

BACKGROUND: The autoinducible metabolic transformation of the anticancer agent ifosfamide involves activation through 4-hydroxyifosfamide to the ultimate cytotoxic ifosforamide mustard and deactivation to 2- and 3-dechloroethylifosfamide with concomitant release of the neurotoxic chloroacetaldehyde. Activation is mediated by cytochrome P450 (CYP) 3A4 and deactivation by CYP3A4 and CYP2B6. The aim of this study was to investigate modulation of the CYP-mediated metabolism of ifosfamide with ketoconazole, a potent inhibitor of CYP3A4, and rifampin (INN, rifampicin), an inducer of CYP3A4/CYP2B6. METHODS: In a double-randomized, 2-way crossover study a total of 16 patients received ifosfamide 3 g/m(2) per 24 hours intravenously, either alone or in combination with 200 mg ketoconazole twice daily (1 day before treatment and 3 days of concomitant administration) or 300 mg rifampin twice daily (3 days before treatment and 3 days of concomitant administration). Plasma pharmacokinetics and urinary excretion of ifosfamide, 2- and 3-dechloroethylifosfamide, and 4-hydroxyifosfamide were assessed in both courses. Data analysis was performed with a population pharmacokinetic model with a description of autoinduction of ifosfamide. RESULTS: Rifampin increased the clearance of ifosfamide at the start of therapy at 102%. The fraction of ifosfamide metabolized to the dechloroethylated metabolites was increased, whereas exposure to the metabolites was decreased as a result of increased elimination. The fraction metabolized and the exposure to 4-hydroxyifosfamide were not significantly influenced. Ketoconazole did not affect the fraction metabolized or the exposure to the dechloroethylated metabolites, whereas both parameters were reduced with 4-hydroxyifosfamide. CONCLUSIONS: Coadministration of ifosfamide with ketoconazole or rifampin did not produce changes in the pharmacokinetics of the parent or metabolites that may result in an increased benefit of ifosfamide therapy.

Adult↗
PubMed2001

Zinc cyanamide, Zn(CN2).

Single crystals of the title compound have been grown by annealing microcrystalline zinc cyanamide at 843 K in silver crucibles. Zn(CN(2)) crystallizes as colourless prisms. The crystal structure is composed of corner-linked ZnN(4/2) tetrahedra. Carbon and nitrogen form (CN(2))(2-) dumb-bells with the C atom on a twofold axis. Nitrogen is approximately trigonally planar, coordinated by two Zn atoms and one C atom.

Journal Article↗
PubMed2001

Reversible phase transitions in Na2S under pressure: a comparison with the cation array in Na2SO4.

The structural behavior of the antifluorite Na(2)S, disodium sulfide, has been studied under pressure up to 22 GPa by in situ synchrotron X-ray diffraction experiments in a diamond anvil cell at room temperature. At approximately 7 GPa, Na(2)S undergoes a first phase transition to the orthorhombic anticotunnite (PbCl(2)) structure (Pnma, Z = 4). The lattice parameters at 8.2 GPa are a = 6.707 (5), b = 4.120 (3), c = 8.025 (4) A. At approximately 16 GPa, Na(2)S undergoes a second transition adopting the structure of the Ni(2)In-type (P6(3)/mmc, Z = 2). The lattice parameters at 16.6 GPa are a = 4.376 (18), c = 5.856 (9) A. Both pressure-induced phases have been confirmed by full Rietveld refinements. An inspection of the cation array of Na(2)SO(4) reveals that its Na(2)S subarray is also of the Ni(2)In-type. This feature represents a new example of how the cation arrangements in ternary oxides correspond to the topology of the respective binary compounds. We discuss analogies between the insertion of oxygen and the application of pressure.

Journal Article↗
PubMed2001

Non-growth-associated demethylation of dimethylsulfoniopropionate by (homo)acetogenic bacteria.

The demethylation of the algal osmolyte dimethylsulfoniopropionate (DMSP) to methylthiopropionate (MTPA) by (homo)acetogenic bacteria was studied. Five Eubacterium limosum strains (including the type strain), Sporomusa ovata DSM 2662(T), Sporomusa sphaeroides DSM 2875(T), and Acetobacterium woodii DSM 1030(T) were shown to demethylate DMSP stoichiometrically to MTPA. The (homo)acetogenic fermentation based on this demethylation did not result in any significant increase in biomass. The analogous demethylation of glycine betaine to dimethylglycine does support growth of acetogens. In batch cultures of E. limosum PM31 DMSP and glycine betaine were demethylated simultaneously. In mixed substrates experiments with fructose-DMSP or methanol-DMSP, DMSP was used rapidly but only after exhaustion of the fructose or the methanol. In steady-state fructose-limited chemostat cultures (at a dilution rate of 0.03 h(-1)) with DMSP as a second reservoir substrate, DMSP was biotransformed to MTPA but this did not result in higher biomass values than in cultures without DMSP; cells from such cultures demethylated DMSP at rates of approximately 50 nmol min(-1) mg of protein(-1), both after growth in the presence of DMSP and after growth in its absence. In cell extracts of glycine betaine-grown strain PM31, DMSP demethylation activities of 21 to 24 nmol min(-1) mg of protein(-1) were detected with tetrahydrofolate as a methyl acceptor; the activities seen with glycine betaine were approximately 10-fold lower. A speculative explanation for the demethylation of DMSP without an obvious benefit for the organism is that the DMSP-demethylating activity is catalyzed by the glycine betaine-demethylating enzyme and that a transport-related factor, in particular a higher energy demand for DMSP transport across the cytoplasmic membrane than for glycine betaine transport, may reduce the overall ATP yield of the fermentation to virtually zero.

Acetyl Coenzyme A↗
PubMed2001

Dehydroepiandrosterone sulfate treatment for atrichia pubis.

OBJECTIVE: To evaluate the efficacy of oral dehydroepiandrosterone sulfate (DHEAS) treatment for atrichia pubis in female adolescents. STUDY DESIGN: Two XY female adolescents with 17-hydroxylase deficiency and 2 XX females with panhypopituitarism presenting with atrichia pubis were treated with a daily dosage of DHEAS 10 mg/m2 body surface in addition to their regular substitution therapy. The dosage was increased according to clinical response. Pubic hair stages, growth and serum DHEAS were evaluated and in 1 case also serum IGFs and IGFBPs. RESULTS: A dosage of 10 mg/m2 for 1 year led to serum DHEAS levels at the lower limit of the normal range. 15 mg/m2 was needed to achieve pubic hair stage 4-5 and axillary hair in patients with 17-hydroxylase deficiency. In panhypopituitarism, pubic hair developed at a slower pace and reached stage 4 on a dosage of 25-30 mg/m2. Baseline serum IGF-I SDS was -0.67 and did not change on the initial dosage of DHEAS, in combination with submaximal estrogen substitution (10 microg ethinyl estradiol). On the combination of 15 mg/m2 DHEAS and full estrogen substitution, IGF-I SDS increased to an average of -0.15. IGFBP-3 SDS increased from 1.4 to a mean of 2.6 in the first year, and went back to 1.4 in the second year. IGFBP-6 SDS was low at baseline (-2.5) and rose to -1.9 and -1.7 IGF-II and IGFBP-1 showed an irregular pattern. CONCLUSIONS: Oral administration of DHEAS in a dosage of 15 mg/m2 o.d. is an efficacious treatment for atrichia pubis. For females with a panhypopituitarism a higher dosage appears needed. Given this and other biological actions of DHEAS, substitution therapy with DHEAS or DHEA to females with adrenal androgen deficiency appears rational.

Administration, Oral↗
PubMed2001

Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene.

The POU homeodomain containing transcriptional activator POU1F1, formerly called Pit1 or GHF-1, is required for the embryological determination and postnatal secretory function of the GH-, PRL-, and TSH-producing cells in the anterior pituitary. Several mutations in the gene encoding POU1F1 have been described, resulting in a syndrome of combined pituitary hormone deficiency involving these three hormones. Most of the patients with this phenotype have either a dominant negative mutation in codon 271 (R271W) or are homozygous for a recessive mutation in the POU1F1 gene; to date only one case has been reported with compound heterozygosity for two point mutations. Here, we describe a boy with severe deficiencies of GH, PRL, and TSH who had compound heterozygosity for two novel point mutations in the POU1F1 gene: a 1-bp deletion frameshift mutation (747delA), the first one described to date in this gene, which leads to a nonfunctional truncated protein lacking the entire DNA recognition helix of the POU homeodomain, and a missense mutation in the C-terminal end of the fourth alpha-helix of the POU-specific domain (W193R),which causes a 500-fold reduction in the ability to bind to DNA and activate transcription.

Cell Line↗
PubMed2001

A randomized controlled trial of three years growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stature and intrauterine growth retardation.

We assessed the effectiveness and safety of 3 yr combined GH and GnRH agonist (GnRHa) treatment in a randomized controlled study in children with idiopathic short stature (ISS) or intrauterine growth retardation (IUGR). Gonadal suppression, GH reserve, and adrenal development were assessed by hormone measurements in both treated children and controls during the study period. Thirty-six short children, 24 girls (16 ISS/8 IUGR) and 12 boys (8 ISS/4 IUGR), with a height SD score of -2 SD or less in early puberty (girls, B2-3; boys, G2-3), were randomly assigned to treatment (n = 18) with GH (genotropin 4 IU/m(2). day) and GnRHa (triptorelin, 3.75 mg/28 days) or no treatment (n = 18). At the start of the study mean (SD) age was 11.4 (0.56) or 12.2 (1.12) yr whereas bone age was 10.7 (0.87) or 10.9 (0.63) yrs in girls and boys, respectively. During 3 yr of study height SD score for chronological age did not change in both treated children and controls, whereas a decreased rate of bone maturation after treatment was observed [mean (SD) 0.55 (0.21) 'yr'/yr vs. 1.15 (0.37) 'yr'/yr in controls, P < 0.001, girls and boys together]. Height SD score for bone age and predicted adult height increased significantly after 3 yr of treatment; compared with controls the predicted adult height gain was 8.0 cm in girls and 10.4 cm in boys. Furthermore, the ratio between sitting height/height SD score decreased significantly in treated children, whereas body mass index was not influenced by treatment. Puberty was effectively arrested in the treated children, as was confirmed by physical examination and prepubertal testosterone and estradiol levels. GH-dependent hormones including serum insulin-like growth factor I and II, carboxy terminal propeptide of type I collagen, amino terminal propeptide of type III collagen, alkaline phosphatase, and osteocalcin were not different between treated children and controls during the study period. Thus, a GH dose of 4 IU/m(2) seems adequate for stabilization of the GH reserve and growth in these GnRHa-treated children. We conclude that 3 yr treatment with GnRHa was effective in suppressing pubertal development and skeletal maturation, whereas the addition of GH preserved growth velocity during treatment. This resulted in a considerable gain in predicted adult height, without demonstrable side effects. Final height results will provide the definite answer on the effectiveness of this combined treatment.

Adolescent↗
PubMed2000

Studies on the interaction between TWEAK and the death receptor WSL-1/TRAMP (DR3).

WSL-1/TRAMP (DR3) is a member of the tumour necrosis factor (TNF) receptor superfamily which exhibits effects on NF-kappaB activation and apoptosis. TWEAK, a novel TNF-related molecule, has been proposed as the ligand for this receptor. Utilising both human and murine TWEAK ligand, it is shown that TWEAK and WSL-1/TRAMP do not interact in an in vitro binding assay and that TWEAK binds strongly to cells that do not express WSL-1/TRAMP on the cell surface. Biological activity of TWEAK is also observed in these cells. Finally, cells isolated from WSL-1/TRAMP knockout mice are shown to retain their ability to interact with TWEAK. These results suggest that WSL-1/TRAMP is not the major receptor for TWEAK

Animals↗
PubMed2000

Inorganic yellow-red pigments without toxic metals

Inorganic pigments have been utilized by mankind since ancient times, and are still widely used to colour materials exposed to elevated temperatures during processing or application. Indeed, in the case of glasses, glazes and ceramics, there is no alternative to inorganic pigments for colouring. However, most inorganic pigments contain heavy metals or transition metals that can adversely effect the environment and human health if critical levels are exceeded. Cadmium-based pigments in particular are a cause of concern: although the pigments are not toxic due to their very low solubility in water and dilute mineral acids, cadmium itself is toxic and can enter the environment in a bioavailable form through waste-disposal sites and incineration plants. This has led to regulations, based on the precautionary principle, that strongly restrict the use of cadmium pigments. And even though recent assessments have concluded that the risk to humans or the environment might be not as significant as originally feared, a strong demand for inherently safer substitutes remains. Here we demonstrate that solid solutions of the perovskites CaTaO2N and LaTaON2 constitute promising candidates for such substitutes: their brilliance, tinting strength, opacity, dispersability, light-fastness and heat stability rival that of the cadmium pigments, while their colour can be tuned through the desired range, from yellow through orange to deep red, by simple composition adjustments. Because all the constituent elements are harmless, this perovskite-based inorganic pigment system seems a promising replacement that could eliminate one of the sources for cadmium emissions to the environment and some of the remaining concerns about pigment safety.

Journal Article↗
PubMed2000

Direct adsorption of lipoproteins (DALI) from whole blood: first long-term clinical experience with a new LDL-apheresis system for the treatment of familial hypercholesterolaemia.

BACKGROUND: The DALI (direct adsorption of lipoproteins) LDL-apheresis system is a novel device for the removal of lipoproteins from whole blood. METHODS: We report the first long-term treatment experience (16.7 +/- 12.6 months; 57 +/- 43 treatments/patient) using different DALI adsorber sizes (DALI-500, DALI-750, DALI-1000) in seven patients with homozygous (n = 1) and severe heterozygous familial hypercholesterolaemia. For each treatment, 1.6 fold of the calculated blood volume was processed. Treatments were scheduled at weekly or two-weekly intervals. RESULTS: The smallest DALI-500 configuration was unable to achieve sufficient removal of LDL cholesterol, with the adsorber being exhausted already at desorption of 65% of the calculated blood volume. In contrast, both larger adsorber systems effectively removed lipoproteins until the end of treatment. Therefore, the DALI-750 device was used for long-term treatment. LDL cholesterol (mean pretreatment value: 179 +/- 44 mg/dl) was reduced by 73.4 +/- 7.7% and Lp(a) levels (mean pretreatment value: 43 +/- 33 mg/dl) by 69.5 +/- 8.3%. HDL cholesterol (mean pretreatment value: 47 +/- 15 mg/dl) was reduced by 16.3 +/- 8.0% during the treatment. In the long term, LDL cholesterol was reduced by 54.0 +/- 10.5%--from 259 +/- 101 mg/dl to 119 +/- 19 mg/dl. No serious side effects occurred during the treatment. Long-term evaluation of other laboratory parameters showed a reduction in haemoglobin due to treatment-associated blood loss despite frequent iron supplementation. CONCLUSION: Sufficient reductions in LDL cholesterol and Lp(a) were achieved using the DALI-750 system and the treatment was well tolerated. The easy use and short period of 153 +/- 22 minutes required for each treatment are the major advantages of the DALI system as compared to other available LDL-apheresis devices. Potential particle release from the adsorber into the circulation must be ruled out before the system can be introduced in clinical routine.

Adult↗