Search PubMed⌕ Search

Biomedical subjects

A Mertens

Publications and source records attributed to A Mertens.

At least 19 recordsLinked to original sources

Survival of He+ ions during grazing scattering from a Ag(111) surface.

He+ ions as well as neutral He atoms with keV energies are scattered under a grazing angle of incidence from a clean and atomically flat Ag(111) surface. From a comparison of ion fractions observed after scattering of He+ ions and He atoms we find for energies below some keV small but defined fractions of ions that have survived the complete scattering event with the surface. This feature allows us to clear up the microscopic interaction scenario for Auger neutralization of He+ ions at a Ag(111) surface. The Auger neutralization rates are 2 to 3 orders of magnitude smaller than conventional rates derived from experiments for He+-metal systems and agree with recent calculations.

Journal Article↗

Evidence for F(-) formation by simultaneous double-electron capture during scattering of F(+) from a LiF(001) surface.

Slow F(+) ions (v<0.1 a.u.) scattered from a clean and flat LiF(001) surface under a grazing angle of incidence exhibit a high probability for forming F(-) ions in the reflected beam, whereas no negative ions are found for neutral F(0) projectiles. From detailed studies of projectile energy loss and charge transfer, we find evidence for a correlated double-electron capture process in the formation of the F(-) ions.

Journal Article↗

Adenovirus-mediated gene transfer of human platelet-activating factor-acetylhydrolase prevents injury-induced neointima formation and reduces spontaneous atherosclerosis in apolipoprotein E-deficient mice.

BACKGROUND: Atherosclerosis is characterized by an early inflammatory response involving proinflammatory mediators such as platelet-activating factor (PAF)-like phospholipids, which are inactivated by PAF-acetylhydrolase (PAF-AH). The effect of adenovirus-mediated expression of PAF-AH on injury-induced neointima formation and spontaneous atherosclerosis was studied in apolipoprotein E-deficient mice. METHODS AND RESULTS: Intravenous administration of an adenovirus (5 x 10(8) plaque-forming units) directing liver-specific expression of human PAF-AH resulted in a 3.5-fold increase of plasma PAF-AH activity at day 7 (P<0.001); this was associated with a 2.4- and 2.3-fold decrease in malondialdehyde-modified LDL autoantibodies and the lysophosphatidylcholine/phosphatidylcholine ratio, respectively (P<0.001 for both). Non-HDL and HDL cholesterol levels in PAF-AH-treated mice were similar to those of control virus-treated mice. Seven days after virus injection, endothelial denudation of the common left carotid artery was induced with a guidewire. Neointima formation was assessed 18 days later. PAF-AH gene transfer reduced oxidized lipoproteins by 82% (P<0.001), macrophages by 69% (P=0.006), and smooth muscle cells by 84% (P=0.002) in the arterial wall. This resulted in a 77% reduction (P<0.001) of neointimal area. Six weeks after adenovirus-mediated gene transfer, spontaneous atherosclerotic lesions in the aortic root were analyzed. PAF-AH gene transfer reduced atherosclerotic lesions by 42% (P=0.02) in male mice, whereas a nonsignificant 14% reduction was observed in female mice. Basal and PAF-AH activity after gene transfer were higher in male mice than in female mice (P=0.01 and P=0.04, respectively). CONCLUSIONS: Gene transfer of PAF-AH inhibited injury-induced neointima formation and spontaneous atherosclerosis in apolipoprotein E-deficient mice. Our data indicate that PAF-AH, by reducing oxidized lipoprotein accumulation, is a potent protective enzyme against atherosclerosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Slow-release tramadol for treatment of chronic malignant pain--an open multicenter trial.

Patients with moderate to severe cancer pain and insufficient pain relief from nonopioid analgesics were treated with slow-release tramadol for initial dose finding and as a long-term treatment. Immediate-release tramadol was provided for the treatment of breakthrough pain and a standard nonopioid analgesic (1000 mg naproxen daily) was given as suggested for step 2 of the WHO analgesic ladder. Ninety of 146 patients (62%) completed the 6-week trial period. Drop-outs were due to adverse events (20%), inadequate pain relief (9%), or both (2.5%), death due to the underlying disease (4%), low patient compliance (2%) or other reasons. Average and maximal pain intensity decreased from day 1 to day 4. The number of patients with good and complete pain relief increased from 43% after week 1 to 71% after week 6 with maximum daily doses of tramadol up to 650 mg. However, 70% of the patients still needed less than 400 mg tramadol per day in week 6. Most patients (86%) experienced adverse events during the study period. Some common side effects of opioids, such as fatigue, dizziness, and constipation, decreased in frequency over the 6 weeks. The frequency of other adverse events such as nausea, vomiting and sweating did not change. Slow-release tramadol provided fast and efficient pain relief in almost two-thirds of patients both during initial dose finding and during long-term treatment, improving treatment options in step 2 of the WHO analgesic ladder.

Adult↗

Oxidized LDL and HDL: antagonists in atherothrombosis.

Increased LDL oxidation is associated with coronary artery disease. The predictive value of circulating oxidized LDL is additive to the Global Risk Assessment Score for cardiovascular risk prediction based on age, gender, total and HDL cholesterol, diabetes, hypertension, and smoking. Circulating oxidized LDL does not originate from extensive metal ion-induced oxidation in the blood but from mild oxidation in the arterial wall by cell-associated lipoxygenase and/or myeloperoxidase. Oxidized LDL induces atherosclerosis by stimulating monocyte infiltration and smooth muscle cell migration and proliferation. It contributes to atherothrombosis by inducing endothelial cell apoptosis, and thus plaque erosion, by impairing the anticoagulant balance in endothelium, stimulating tissue factor production by smooth muscle cells, and inducing apoptosis in macrophages. HDL cholesterol levels are inversely related to risk of coronary artery disease. HDL prevents atherosclerosis by reverting the stimulatory effect of oxidized LDL on monocyte infiltration. The HDL-associated enzyme paraoxonase inhibits the oxidation of LDL. PAF-acetyl hydrolase, which circulates in association with HDL and is produced in the arterial wall by macrophages, degrades bioactive oxidized phospholipids. Both enzymes actively protect hypercholesterolemic mice against atherosclerosis. Oxidized LDL inhibits these enzymes. Thus, oxidized LDL and HDL are indeed antagonists in the development of cardiovascular disease.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease.

Our aim was to determine the usefulness of circulating oxidized low density lipoprotein (LDL) in the identification of patients with coronary artery disease (CAD). A total of 304 subjects were studied: 178 patients with angiographically proven CAD and 126 age-matched subjects without clinical evidence of cardiovascular disease. The Global Risk Assessment Score (GRAS) was calculated on the basis of age, total and high density lipoprotein cholesterol, blood pressure, diabetes mellitus, and smoking. Levels of circulating oxidized LDL were measured in a monoclonal antibody 4E6-based competition ELISA. Compared with control subjects, CAD patients had higher levels of circulating oxidized LDL (P<0.001) and a higher GRAS (P<0.001). The sensitivity for CAD was 76% for circulating oxidized LDL (55% for men and 81% for women) compared with 20% (24% for men and 12% for women) for GRAS, with a specificity of 90%. Logistic regression analysis revealed that the predictive value of oxidized LDL was additive to that of GRAS (P<0.001). Ninety-four percent of the subjects with high (exceeding the 90th percentile of distribution in control subjects) circulating oxidized LDL and high GRAS had CAD (94% of the men and 100% of the women). Thus, circulating oxidized LDL is a sensitive marker of CAD. Addition of oxidized LDL to the established risk factors may improve cardiovascular risk prediction.

Aged↗

Arg123-Tyr166 domain of human ApoA-I is critical for HDL-mediated inhibition of macrophage homing and early atherosclerosis in mice.

Atherosclerosis was studied in apolipoprotein E (apoE) knockout mice expressing human apolipoprotein A-I (apoA-I) or an apoA-I/apolipoprotein A-II (apoA-II) chimera in which the Arg123-Tyr166 central domain of apoA-I was substituted with the Ser12-Ala75 segment of apoA-II. High density lipoprotein (HDL) cholesterol levels were identical in apoA-I and apoA-I/apoA-II mice, but at 4 months, plaques were 2.7-fold larger in the aortic root of the apoA-I/apoA-II mice (P<0.01). The macrophage-to-smooth muscle cell ratio of lesions was 2.1-fold higher in apo-I/apoA-II mice than in apoA-I mice (P<0.01). This was due to a 2.7-fold higher (P<0.001) in vivo macrophage homing in the aortic root of apoA-I/apoA-II mice. Plasma platelet-activating factor acetyl hydrolase activity was lower (P<0.01) in apoA-I/apoA-II mice, resulting in increased oxidative stress, as evidenced by the higher titer of antibodies against oxidized low density lipoprotein (P<0.01). Increased oxidative stress resulted in increased stimulation of ex vivo macrophage adhesion by apoA-I/apoA-II beta-very low density lipoprotein and decreased inhibition of beta-very low density lipoprotein-induced adhesion by HDL from apoA-I/apoA-II mice. The cellular cholesterol efflux capacity of HDL from apoA-I/apoA-II mice was very similar to that of apoA-I mice. Thus, the Arg123-Tyr166 central domain of apoA-I is critical for reducing oxidative stress, macrophage homing, and early atherosclerosis in apoE knockout mice independent of its role in HDL production and cholesterol efflux.

Animals↗

The effect of atorvastatin on postprandial lipaemia in overweight or obese women homozygous for apo E3.

OBJECTIVE: To determine the effect of atorvastatin on postprandial lipaemia in overweight or obese women with the apoprotein (apo) E3/E3 genotype. DESIGN: Double-blind randomised, placebo-controlled 8-week single-centre study. SUBJECTS: Twenty-two healthy women, homozygous for apo E3 with a BMI ranging from 27.6 to 41.1 kg/m2 and normal or moderately elevated fasting triglycerides (53-184 mg/dl). TREATMENT: After a 4-week isocaloric single-blind, placebo lead-in period, subjects were randomly assigned to receive either placebo (n = 7) or atorvastatin 20 mg once daily in the evening (n = 15) for 4 weeks. RESULTS: Atorvastatin significantly reduces fasting total cholesterol, LDL-cholesterol and postprandial triglycerides in obese women, homozygous for apo E3 with normal or near-normal fasting triglyceride levels. No significant effect on fasting triglycerides was observed. CONCLUSION: Atorvastatin decreases postprandial hyperlipidaemia, an independent cardiovascular risk factor, in normolipidaemic obese women. This effect of atorvastatin may, therefore, represent a cardioprotective mechanism.

Adult↗

Adipose tissue expression of gelatinases in mouse models of obesity.

Following the observation by Brown et al. (Am J Physiol 1997; 272: C937-49) that primary rat adipocytes in culture secrete gelatinase A (MMP-2), we have evaluated gelatinase expression in adipose tissue with the use of mouse models of obesity. Wild-type mice were kept on a standard fat diet (SFD) or on a high fat diet (42% fat, HFD) and- genetically obese db/db mice were kept on SFD; gonadal and subcutaneous fat pads were removed and analysed ex vivo. These studies revealed that: 1) the HFD induced adipocyte hypertrophy; 2) after 32 weeks, significantly higher levels of 70 kDa (p <0.05) and 65 kDa proMMP-2 (p <0.01) were observed in extracts of gonadal fat pads of mice on HFD; 3) the contribution of active MMP-2 to the total level was comparable in SFD and HFD groups (20 to 30%); and 4) gelatinase B (MMP-9) was not consistently detected. These findings were confirmed by gelatin zymography and by mRNA determination using competitive RT-PCR. The presence of MMP-2 in the adipose tissue was confirmed immunologically and its localization in adipocytes revealed by immunogold electron microscopy. The potential functional role of MMP-2 in adipose tissue remains to be determined.

Adipose Tissue↗

Corneal opacifications in a low high density lipoprotein syndrome: suspicion of fish eye disease: a case report.

A 49 year old patient with progressive massive bilateral corneal opacifications associated with a HDL (high-density-lipoprotein) deficiency is described. The opacifications started at the age of twenty and progressed slowly. They were found diffusely over the cornea, though more in the corneal periphery. A penetrating keratoplasty at the right eye was performed. The diagnosis of Fish Eye Disease was put forward on the basis of the ophthalmological, clinical, biochemical and pathological appearance. After 2 year follow-up, the graft was clear. The final distance and near vision of the right eye was 8/10 and Snellen 1 respectively.

Adult↗

Energy transfer from fast atomic projectiles to a crystal lattice under channeling conditions

Neutral Ne atoms with keV energies are scattered under channeling conditions, i.e., at a glancing angle of incidence, from a LiF(001) surface. By means of a time-of-flight method with a pulsed neutral beam, energy distributions for scattered projectiles are obtained. We find for this specific system that the small energy transferred to the crystal lattice during channeling via binary collisions with large impact parameters dominates the dissipation of projectile energy, whereas all other excitations of the solid can be brought to a negligible level.

Journal Article↗

Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study.

Treatment for Hodgkin's disease (HD) is associated with a variety of thyroid abnormalities, including hypothyroidism, hyperthyroidism, and thyroid neoplasms. Due to the small sample size and short follow-up time of most published studies, it has been difficult to appreciate the full extent of the problem and to characterize the interaction between various patient and treatment variables. To overcome these limitations we have assessed thyroid status in 1,791 (959 males) HD survivors from among 13,674 participants in the Childhood Cancer Survivor Study, a cohort of 5-yr survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. Thyroid abnormalities were ascertained as part of a 22-page questionnaire sent to participants. Survivors were a median of 14 yr (range, 2-20 yr) at diagnosis of HD and a median of 30 yr (range, 12-47 yr) at follow-up. Seventy-nine percent of subjects were treated with radiation (median dose of radiation to the thyroid, 3,500 cGy; range, 0.37-5,500 cGy). Control data were available from 2,808 (1,346 males) sibling controls. Thirty-four percent of the entire cohort has been diagnosed with at least one thyroid abnormality. Hypothyroidism was the most common disturbance, with a relative risk of 17.1 (P < 0.0001) compared to sibling controls. Increasing dose of radiation, older age at diagnosis of HD, and female sex were all independently associated with an increased risk of hypothyroidism. Actuarial risk of hypothyroidism for subjects treated with 4,500 cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism was reported by 5% of survivors, which was 8-fold greater (P < 0.0001) than the incidence reported by the controls. Thyroid dose of 3,500 cGy or more was the only risk factor identified for hyperthyroidism. The risk of thyroid nodules was 27 times (P < 0.0001) that in sibling controls. Female sex and radiation dose to the thyroid of 2,500 cGy or more were independent risk factors for thyroid nodules. The actuarial risk of a female survivor developing a thyroid nodule is 20% at 20 yr from diagnosis. Thyroid cancer was diagnosed in 20 survivors, which is 18 times the expected rate for the general population. After taking into account the possibility that some of the relative risk estimates may be exaggerated due to ascertainment bias, abnormalities of the thyroid are still extremely common in young adult survivors of childhood HD, particularly among females treated with high doses of radiation to the neck.

Adolescent↗

Marriage in the survivors of childhood cancer: a preliminary description from the Childhood Cancer Survivor Study.

BACKGROUND: The goal of this paper is to provide a preliminary description of the marital status for a large number of childhood cancer survivors participating in the Childhood Cancer Survivor Study (CCSS). PROCEDURE: This report includes children and adolescents (< 21 years of age) diagnosed with cancer between 1970 and 1986 at 25 oncology centers in the United States and Canada who survived at least 5 years from diagnosis. Self-reported data from 10,425 survivors are used in this preliminary descriptive summary. The proportion of survivors ever married and divorced/separated is compared to the U.S. population according to age-specific groups. The median age of the survivor population at diagnosis was 7 years and 26 years at the time martial status was ascertained. Excluded from this assessment are children < 15 years of age at the time of study, those whose martial status was unknown, and those married prior to diagnosis. Data for marital status of the U.S. population, as tabulated in the Bureau of Census 1995 Update, is used as a general comparison to the survivor population. RESULTS: Overall, 32% of the survivors reported being married or living as married, 6% being divorced or separated, 0% being widowed, and 62% having never been married. In general, compared to the U.S. population, survivors were less likely to have ever married, particularly females and whites, but, once married, were less likely to divorce/separate, again particularly females and whites. Black survivors were generally found to be more likely to have married, with males and blacks more likely to divorce/separate once married. Comparison of childhood tumor types suggested that survivors of CNS tumors, particularly males, were less likely to have ever married and more likely to divorce/separate compared to those with other cancer diagnoses and the general U.S. population. CONCLUSIONS: This interim evaluation of the CCSS cohort provided preliminary data describing a suggested decreased likelihood of marriage, which may be influenced by gender and/or race. These patterns must be confirmed within the entire CCSS cohort and comparisons made with an appropriate sibling comparison group before making final conclusions.

Adolescent↗

Determinants of postprandial lipemia in obese women.

OBJECTIVE: To quantify the effects of fasting lipids, age, apolipoprotein (apo) E polymorphism, insulin resistance, body fat and abdominal fat distribution, on postprandial lipemia (PPL) in non-diabetic obese women. DESIGN: Cross-sectional, prospective. SUBJECTS: A total of 93 obese women (mean +/- s.d. age 39+/-13y; body mass index (BMI) 38.3+/-4.9 kg/m2) and 16 nonobese women (25+/-8y; BMI 22.7+/-3.2 kg/m2). MEASUREMENTS: Body fat distribution was determined by the ratio of waist-to-hip circumferences (WHR) and by computed tomography (CT) at the L4-L5 level. Apo E genotyping was performed by restriction isotyping. Insulin resistance was calculated from fasting glucose and insulin concentrations. PPL was evaluated using the vitamin A-fat tolerance test (1.0 g fat/kg body weight and 7.0 mg cholesterol/kg body weight+300000 IU vitamin A palmitate). Blood samples were drawn before, and every 1.5 h for 7.5 h plus 24 h after ingestion of the fat meal. Areas under the response curves (AUC) for triglycerides (TG) and retinyl palmitate (RP) were calculated using the geometrical method for two time intervals, that is, 0-7.5 h and 0-24 h. RESULTS: Incremental AUCs TG, but not AUCs RP, were increased in the obese women. Apo E polymorphism, BMI, WHR and menopausal state did not influence PPL in the obese women. Fasting TG, age, the intra-abdominal to subcutaneous abdominal fat ratio (IA/SC ratio) and insulin resistance were independent determinants of PPL. Together, fasting TG, IA/SC ratio and insulin resistance, explained 38% of the variance in AUC TG 0-7.5 h (P = 0.0001). CONCLUSION: Alterations in PPL are to be added to the increasing number of components of the plurimetabolic syndrome.

Adolescent↗

Epidemiologic study of Langerhans cell histiocytosis in children.

OBJECTIVE: The etiology and pathogenesis of Langerhans cell histiocytosis (LCH) remain poorly understood. We conducted an exploratory epidemiologic study to investigate potential risk factors associated with LCH. STUDY DESIGN: We used a case-control study design to obtain data from parents of children with LCH (n = 459) who were members of the Histiocytosis Association of America and Canada. The two control groups consisted of 683 community control subjects and 3719 children with childhood cancers treated at participating Children's Cancer Group institutions. RESULTS: The median age at diagnosis of LCH was 1.8 years (range 0.1 to 14.6 years). Cases were categorized as multisystem LCH (MS-LCH) (n = 208) and single-system LCH (SS-LCH) (n = 198). Statistically significant associations included the following: infections in the neonatal period (MS-LCH, odds ratio (OR) = 2.2), solvent exposure (SS-LCH, OR = 54.9), childhood vaccinations (MS-LCH and SS-LCH, OR = 0.4), thyroid disease in the proband (MS-LCH and SS-LCH, OR = 21.6), and family history of thyroid disease (MS-LCH and SS-LCH, OR = 1.4). The association with thyroid disease in the proband was explained partially by the involvement of the pituitary, with the relative risk decreasing when patients with diabetes insipidus and thyroid involvement were excluded from analysis. CONCLUSIONS: This large hypothesis-generating study provides directions for future investigations in well-designed population-based or hospital-based epidemiologic studies.

Adolescent↗