Characterization of the

The isotope ^{163}Ho is in many ways the best candidate to perform experiments to investigate the value of the electron neutrino mass. It undergoes an electron capture process to ^{163}Dy with an energy available to the decay, Q_{EC}, of about 2.8 keV. According to the present knowledge, this is the lowest Q_{EC} value for such transitions. Here we discuss a newly obtained spectrum of ^{163}Ho, taken by cryogenic metallic magnetic calorimeters with ^{163}Ho implanted in the absorbers and operated in anticoincident mode for background reduction. For the first time, the atomic deexcitation of the ^{163}Dy daughter atom following the capture of electrons from the 5s shell in ^{163}Ho, the OI line, was observed with a calorimetric measurement. The peak energy is determined to be 48 eV. In addition, a precise determination of the energy available for the decay Q_{EC}=(2.858±0.010_{stat}±0.05_{syst}) keV was obtained by analyzing the intensities of the lines in the spectrum. This value is in good agreement with the measurement of the mass difference between ^{163}Ho and ^{163}Dy obtained by Penning-trap mass spectrometry, demonstrating the reliability of the calorimetric technique.

Visualization of spin dynamics in single nanosized magnetic elements.

The design of future spintronic devices requires a quantitative understanding of the microscopic linear and nonlinear spin relaxation processes governing the magnetization reversal in nanometer-scale ferromagnetic systems. Ferromagnetic resonance is the method of choice for a quantitative analysis of relaxation rates, magnetic anisotropy and susceptibility in a single experiment. The approach offers the possibility of coherent control and manipulation of nanoscaled structures by microwave irradiation. Here, we analyze the different excitation modes in a single nanometer-sized ferromagnetic stripe. Measurements are performed using a microresonator set-up which offers a sensitivity to quantitatively analyze the dynamic and static magnetic properties of single nanomagnets with volumes of (100 nm)(3). Uniform as well as non-uniform volume modes of the spin wave excitation spectrum are identified and found to be in excellent agreement with the results of micromagnetic simulations which allow the visualization of the spatial distribution of these modes in the nanostructures.

Magnetism of single-crystalline Fe nanostructures.

The quantitative investigation of magnetic nanostructures by means of ferromagnetic resonance is demonstrated for single-crystalline iron nanostructures. It is shown that the single-crystalline nature leads to effects not being present in polycrystalline ones and helps to quantitatively interpret the results. First a method is presented that enables one to fabricate epitaxial Fe nanowires starting from a thin film of Fe grown under ultrahigh vacuum conditions on GaAs (110). The system allows, due to the combination of cubic and twofold magnetic anisotropy, to prepare wires whose easy axis in remanence is oriented perpendicular to the wires axis. This unique feature is only achievable in epitaxial systems. Furthermore, nearly perfect Fe nanocubes with 13.6 nm edge length prepared by wet-chemical methods are studied. While the shell of the particles is composed of either Fe3O4 or gamma-Fe2O3, the core consists of metallic Fe. Oxygen and hydrogen plasma are used to remove the ligand system and the oxide shell. The single-crystalline nature of the cubes enables one to quantitatively determine the magnetic properties of the individual particle by means of ferromagnetic resonance measurements on an ensemble together with a model based on the Landau-Lifshitz equation. The measurements reveal a magneto-crystalline anisotropy of K4 = 4.8. 10(4) J/m3 being equal to bulk value and a saturation magnetization which is reduced to M(5K) = (1.2 +/- 0.12). 10(6) A/m (70% of bulk value). The effective damping parameter alpha = 0.03 is increased by one order of magnitude with respect to bulk Fe, showing that magnetic damping in nanostructures differs from the bulk.

Resistance of a single domain wall in (Co/Pt)7 multilayer nanowires.

Single (Co/Pt)_{7} multilayer nanowires prepared by electron beam lithography with perpendicular magnetic anisotropy are locally modified by means of Ga-ion implantation generating 180 degrees domain walls which are pinned at the edges of underlying thin Pt wires. Since we can exclude contributions from the anisotropic and the Lorentz magnetoresistance this allows us to determine the resistance of a single domain wall at room temperature. We find a positive relative resistance increase of DeltaR/R=1.8% inside the domain wall which agrees well with the model of Levy and Zhang [Phys. Rev. Lett. 79, 5110 (1997)10.1103/PhysRevLett.79.5110].

Impact of hospital-wide surveillance on hospital-acquired infections in an acute-care hospital in the Netherlands.

The goal of surveillance is to identify hospital-acquired infections (HAI) and risk factors, to apply targeted interventions and to evaluate their effect in an ongoing system. Continuing active surveillance in a 270-bed acute-care hospital is being performed on clinical patients, excluding day-care. The period 1984-1997 is described here. Specific surveillance-based interventions included the introduction of antimicrobial prophylaxis in gynaecology patients with postoperative urinary tract catheters and inpatients scheduled for appendicectomy and hysterectomy. General measures included education, implementation of protocols, feedback of surgeon-specific infection rates. In total, 3545 HAI were found in 13 years of surveillance. The incidence was 4.7/100 admissions and 4. 5/1000 patient days. Age-specific incidences ranged from 1.3 in the age-category 1-14 years, to 10.2 in patients aged 75 years and above. If age-specific incidences had remained at their 1984 level, over 3000 additional infections would have occurred, affecting all age groups except those up to 14 years. The distribution of types of infections differed between services. Following the targeted interventions, the rate of infections in gynaecology decreased from 19.4 per 1000 patient days in 1984 to 2.4 per 1000 patient days in 1996. The rates of wound infection following appendicectomy and hysterectomy decreased by 69% and 82%, respectively, in the period following the institution of antimicrobial prophylaxis. Over 4000 micro-organisms were isolated from the HAI; multi-resistant strains were isolated sporadically. We conclude that hospital-wide surveillance of hospital-acquired infections provides appropriate targets for interventions tailored to the specific needs of the hospital. The impact of such interventions can readily be documented from the surveillance data.

Animal models: new cholesterol raising and lowering nutrients.

Most reports reviewed here have used animal models to investigate the cholesterolemic effects of phytochemicals, herbal extracts, probiotic microorganisms, and plant constituents, including fibers. These compounds represent examples of what are termed 'functional foods' in that they elicit physiologic responses with implications for chronic disease prevention. These reports are examined in light of criteria developed from animal model experiments investigating fatty acid effects in order to aid the task of appropriate extrapolation of the results to humans.

Dietary stearic acid reduces plasma and hepatic cholesterol concentrations without increasing bile acid excretion in cholesterol-fed hamsters.

Although there is general agreement that saturated fatty acids elevate plasma cholesterol concentrations, the relative effects of individual fatty acids on cholesterol and bile acid metabolism are less clear. In this study, cholesterol and bile acid responses to diets enriched in different saturated fatty acids were investigated in hamsters. The six diets examined were as follows: 5% fat (g/100 g) enriched in palmitic acid (16:0) with no cholesterol, 5% fat 16:0-enriched, 0.05% cholesterol (wt/wt), and four diets containing 0.05% cholesterol and 15% fat with each diet enriched in lauric (12:0), myristic (14:0), palmitic (16:0), or stearic acid (18:0). Total plasma cholesterol concentration was significantly greater in hamsters fed the 14:0-enriched diet relative to those fed the 18:0-enriched diet (P < 0.05). Both plasma and liver cholesterol concentrations of hamsters fed 18:0 did not differ from those of the group fed no dietary cholesterol. In all instances, differences in total plasma cholesterol were accounted for within the HDL fraction; no significant treatment differences in VLDL or LDL cholesterol were found. Total daily fecal bile acid excretion was higher in hamsters fed the 15% fat 16:0 diet compared with those fed no dietary cholesterol (P < 0.05), but not significantly different from other treatment groups. There was greater deoxycholic acid excretion (P < 0.05) from hamsters fed the 14:0 and 16:0 diets compared with those fed the 18:0-enriched diet. Small intestinal + gallbladder bile acids, an index of pool size, did not differ significantly among the groups. The observed relative hypocholesterolemic effect of stearic acid was not mediated by increased bile acid excretion.

Cholesterol-lowering effects of modified animal fats in postmenopausal women.

OBJECTIVE: In an attempt to improve the nutritional value of animal fats (including milkfat and lard), two technological approaches (i.e., cholesterol removal by steam distillation and linoleic acid enrichment by addition of safflower oil) were tested for cholesterolemic effects in a cohort of 29 older women (age 68 +/- 7 years). METHODS: Test fat sources were incorporated into crackers, cookies, cheese, ice cream, whipped topping, sour cream, baking shortening, and table spreads. Subjects were permanent residents of a convent where meals were prepared in a centralized kitchen, allowing test fats to be provided in daily food menu items. The foods containing test fats were introduced into three sequential dietary treatment periods, each lasting 4 weeks, in the following order: cholesterol-reduced animal fat (CRAF): fatty-acid modified, cholesterol-reduced animal fat (FAMCRAF); and-unaltered animal fat (AF). Subjects were offered menu items cafeteria style and encouraged to make food selections consistent with their habitual diets, which were recorded daily. RESULTS: Fasted blood lipid profiles determined at the end of each treatment period showed that FAMCRAF reduced mean plasma total cholesterol, LDL cholesterol, and apolipoprotein B concentrations relative to AF (p < 0.05). Mean HDL cholesterol concentrations were not influenced by diet. DISCUSSION: Relative to native products, animal fats modified by cholesterol removal and linoleic acid enrichment reduced plasma total and LDL cholesterol concentrations in a predictable manner similar to that based on studies of men.

Increased intestinal contents viscosity reduces cholesterol absorption efficiency in hamsters fed hydroxypropyl methylcellulose.

This study was conducted to test the hypothesis that increased intestinal contents viscosity lowers plasma cholesterol concentrations by decreasing cholesterol absorption. Male Golden Syrian hamsters were fed for 4 wk diets containing 0.12% cholesterol, and either 4% cellulose or four different viscosity grades of hydroxypropyl methylcellulose (HPMC). Dietary HPMC confers viscosity in the small intestine but is resistant to fermentation. Cholesterol absorption efficiency was measured using the dual isotope ratio method, and plasma and liver cholesterol concentrations were determined enzymatically. Ex vivo viscosity of intestinal contents supernatants was measured using a Wells-Brookfield cone/plate viscometer, and the means of treatment groups ranged from 6 to 6532 mPa.s. Relative to dietary cellulose, all viscosity grades of HPMC resulted in significantly lower cholesterol absorption efficiency, lower plasma cholesterol concentration, and lower liver cholesteryl ester content. The logarithm of intestinal contents ex vivo viscosity was inversely correlated with dietary cholesterol absorption (r2 = 0.84, P = 0.028). Furthermore, dietary cholesterol absorption was positively correlated with plasma cholesterol concentration (r2 = 0.89, P = 0.017) and liver cholesteryl ester content (r2 = 0.96, P = 0.0031). Thus, the data suggest an independent role of intestinal contents viscosity in lowering plasma cholesterol concentration and liver cholesteryl ester content by reducing cholesterol absorption efficiency.

Atherogenic and anti-atherogenic factors in the human diet.

New atherosclerosis causative factors and preventive modalities have been identified. Atherogenic factors include lipid oxidation products, such as cholesterol oxidation products, malonaldehyde and other aldehydes; trans-fatty acids; some saturated fatty acids (lauric, myristic and possibly palmitic acids); and myristic acid plus cholesterol. Lipid oxidation products are well suited to induce arterial damage, based on their known cytotoxic effects; evidence also indicates the possibility of plaque promotion and stimulation of thrombogenesis. Anti-atherogenic factors include antioxidants, fish oils and other polyunsaturates (if protected from oxidation), fibre and trace minerals such as copper, manganese, selenium and zinc. Iron is unique, being considered as both a potential promoter of atherosclerosis (component of ferritin, conceivably inducing lipid oxidation) and a possible anti-atherogenic component (of antioxidant enzyme catalase). It is apparent that an entire new series of research challenges has been uncovered.

Relationships between viscosity of hydroxypropyl methylcellulose and plasma cholesterol in hamsters.

Dietary high viscosity hydroxypropyl methylcellulose (HPMC) lowered plasma and liver cholesterol concentrations in cholesterol-fed hamsters. To determine the level of viscosity needed to effect a significant reduction in total plasma cholesterol, hamsters were fed for 3 wk diets containing 0.12% cholesterol and either 4% cellulose or one of four preparations of HPMC that varied in viscosity between 14 and 1698 centipoise (cP), as estimated in vitro. Blood was collected for plasma cholesterol determination, and intestinal contents were obtained by finger-stripping of the excised small intestine. Contents were centrifuged and the supernatant (ex vivo) viscosity determined. In vitro and ex vivo viscosities were correlated (R2 = 0.96). Plasma cholesterol concentrations declined as in vitro or ex vivo viscosity increased. Maximal plasma cholesterol reduction occurred at an ex vivo viscosity of approximately 150 cP. There was a linear relationship between plasma cholesterol and the logarithm of ex vivo viscosity (R2 = 0.98). Our results suggest that materials that increase the viscosity of intestinal contents can be effective in reducing plasma cholesterol and that only moderate increases in viscosity are necessary to achieve this effect.

Viscosity and fermentability as attributes of dietary fiber responsible for the hypocholesterolemic effect in hamsters.

The attribute(s) of soluble dietary fibers responsible for cholesterol lowering is currently uncertain. A series of experiments were conducted in which viscosity and fermentability was assessed independently for their effect on plasma and liver cholesterol concentration. Hamsters were divided into four dietary groups and fed diets containing 0.12% cholesterol and 5% fiber as high viscosity hydroxypropyl methylcellulose (HV-HPMC group), low viscosity hydroxypropyl methylcellulose (LV-HPMC group), high viscosity guar gum (HV-GG group) or low viscosity guar gum (LV-GG group). Hydroxypropyl methylcellulose is essentially nonfermentable, whereas guar gum is highly fermentable. Plasma cholesterol concentrations at 3, 6 and 11 wk and liver cholesterol concentrations at 6 and 11 wk were significantly lower in the HV-HPMC group relative to the LV-HPMC group (P < 0.05). Intestinal content viscosities of the LV-HPMC and HV-GG groups were similar; consequently, these two groups were compared to examine the independent effect of fermentation. Plasma and liver cholesterol were significantly lower in the HV-GG group compared with the LV-HPMC group at 6 wk (P < 0.05), but not at 3 or 11 wk. Hepatic sterol synthesis rates were not affected by any of the diets. This study shows that greater viscosity of intestinal contents is strongly associated with cholesterol reduction, but that the contribution of fiber fermentation remains uncertain.

Nitrogen metabolism in the facultative methylotroph Arthrobacter P1 grown with various amines or ammonia as nitrogen sources.

The metabolism of trimethylamine (TMA) and dimethylamine (DMA) in Arthrobacter P1 involved the enzymes TMA monooxygenase and trimethylamine-N-oxide (TMA-NO) demethylase, and DMA monooxygenase, respectively. The methylamine and formaldehyde produced were further metabolized via a primary amine oxidase and the ribulose monophosphate (RuMP) cycle. The amine oxidase showed activity with various aliphatic primary amines and benzylamine. The organism was able to use methylamine, ethylamine and propylamine as carbon- and nitrogen sources for growth. Butylamine and benzylamine only functioned as nitrogen sources. Growth on glucose with ethylamine, propylamine, butylamine and benzylamine resulted in accumulation of the respective aldehydes. In case of ethylamine and propylamine this was due to repression by glucose of the synthesis of the aldehyde dehydrogenase(s) required for their further metabolism. Growth on glucose/methylamine did not result in repression of the RuMP cycle enzyme hexulose-6-phosphate synthase (HPS). High levels of this enzyme were present in the cells and as a result formaldehyde did not accumulate. Ammonia assimilation in Arthrobacter P1 involved NADP-dependent glutamate dehydrogenase (GDH), NAD-dependent alanine dehydrogenase (ADH) and glutamine synthetase (GS) as key enzymes. In batch cultures both GDH and GS displayed highest levels during growth on acetate with methylamine as the nitrogen source. A further increase in the levels of GS, but not GDH, was observed under ammonia-limited growth conditions in continuous cultures with acetate or glucose as carbon sources.

Alterations in lipid composition and fluidity of liver plasma membranes in copper-deficient rats.

In view of the importance of membrane fluidity on cell functions, the influence of phospholipid acyl groups on membrane fluidity, and the changes in lipid metabolism induced by copper (Cu) deficiency, this study was designed to examine the influence of dietary Cu on the lipid composition and fluidity of liver plasma membranes. Male Sprague-Dawley rats were divided into two dietary treatments, namely Cu deficient and Cu adequate. After 8 weeks of treatment, liver plasma membranes were isolated by sucrose density gradient centrifugation. The lipid fluidity of plasma membranes, as assessed by the intramolecular eximer fluorescence of 1,3-di(1-pyrenyl) propane, was significantly depressed by Cu deficiency. In addition, Cu deficiency significantly reduced the content of arachidonic and palmitoleic acids but increased the docosatetraenoic and docosahexaenoic acids of membrane phospholipids. This alteration in unsaturated phospholipid fatty acid composition, especially the large reduction in arachidonic acid, may have contributed to the depressed membrane fluidity. Furthermore, Cu deficiency also markedly altered the fatty acid composition of the triacylglycerols associated with the plasma membranes. Thus, the lipid composition and fluidity of liver plasma membranes are responsive to the animal's Cu status.

Apolipoprotein E-rich HDL binding to liver plasma membranes in copper-deficient rats.

Copper deficiency in rats raises plasma cholesterol concentration while reducing live cholesterol concentration. One consequence of this cholesterol redistribution is the accumulation of a large high-density lipoprotein (HDL) particle rich in apolipoprotein E (apo E). The purpose of this study was to determine, using an in vitro binding assay, if the interaction of apo E-rich HDL with hepatic lipoprotein binding sites may be affected by copper deficiency. Male Sprague-Dawley rats were divided into two dietary treatments (copper-deficient and -adequate) and placed on a dietary regimen for 8 weeks. Subsequent to exsanguination, hepatic plasma membranes were prepared and apo E-rich HDL was isolated from rats of each treatment by ultracentrifugation, agarose column chromatography, and heparin-Sepharose affinity chromatography. Total binding and experimentally derived specific binding of 125I-apo E-rich HDl to hepatic plasma membranes indicated greater binding when lipoproteins and membranes from copper-deficient animals were used in the assay compared to controls. Scatchard analysis of specific binding data indicated that equilibrium binding affinity (Kd) was also affected by copper deficiency. The hepatic binding sites recognizing apo E-rich HDL were not affected by EDTA or pronase, of relatively high capacity, and recognized a variety of other rat lipoproteins.

Lipoprotein receptors in copper-deficient rats: apolipoprotein E-free high density lipoprotein binding to liver membranes.

Twenty-four male weanling Sprague-Dawley rats were randomly and equally divided into two dietary treatments, copper-deficient and adequate (0.7 mg and 8.0 mg Cu/kg diet, respectively). Deionized water and diet were provided ad libitum. After 8 weeks, rats were exsanguinated, membranes prepared from livers, and plasma high density lipoproteins (HDL) isolated by ultracentrifugation and agarose column chromatography. Heparin-sepharose affinity chromatography was used to isolate subfractions of HDL devoid of apolipoprotein E (apo E-free HDL). The apo E-free HDL derived from rats of each dietary treatment were iodinated and bound to liver membranes prepared from rats of both treatment groups. Total binding data, specific binding data, and computer derived estimates of maximum equilibrium binding (Bmax) indicate less binding was observed when lipoproteins and membranes from copper-deficient animals were used in the binding assay compared to controls. In addition, a 2 X 2 factorial analysis of binding parameters derived from all experiments demonstrated a significant lipoprotein effect, indicating the reduction in binding may be associated with apo E-free HDL obtained from copper-deficient rats. The present findings suggest a reduction in binding of apo E-free HDL to their binding sites may contribute to the hypercholesterolemia and hyperlipoproteinemia observed in copper deficiency.

[Monitoring of heart function in the treatment with cardiotoxic cytostatic drugs]. / Uberwachung der Herzfunktion bei der Behandlung mit kardiotoxisch wirkenden Zytostatika.

UNLABELLED: It is the purpose of this paper to show the concept of noninvasive assessment of cardiomyopathy (CM) in cytostatic treatment, esp. with daunorubicin A (A). Our follow-up study during therapy with A shows 255 patients, examined by ECG, by systolic time intervals (STI)-PEP/LVET (normal value less than or equal to 0.44) and PEPI (normal value less than or equal to 148 ms) by echocardiography (UCG) with measurement of shortening fraction (SF), normal value less than or equal to 30% and in 6 cases by microcatheter with exercise test. RESULTS: (1) ECG does not predict CM. (2) 23 patients (8%) had abnormal SF in UCG, 6 patients of these having no symptoms of cardiac failure. These patients were examined by microcatheter, all 6 having abnormal values during exercise. So all patients with abnormal SF had objective signs of latent or over CM. (3) PEP/LVET was abnormal in all patients with CM, but false positive in 22% of all investigations, mostly by shortening of LVET. PEPI, abnormal in all patients with CM, was false positive only in 8.8. UCG is the most specific noninvasive method for assessment of CM in cytostatic treatment. STI are less specific, but highly sensitive to CM and therefore a useful screening method. PEPI gives the highest specificity, allowing a better selection than PEP/LVET. STI in contrast to UCG can easily be obtained outside cardiologic centers, ie., in the oncologic department itself. UCG by cardiologic units are needed only about 10-15% of investigations. If all values are abnormal, cardiotoxic treatment should be stopped, even when patients are asymptomatic.

Impaired glucose tolerance in copper-deficient rats.

Forty-eight male weanling Sprague-Dawley rats were randomly and equally divided into two dietary treatments (copper-deficient and adequate: 0.85 mg and 8 mg of Cu/kg diet). Deionized water and diet were provided ad libitum. After 5 weeks, the rats were fasted for 18 hours, anesthetized with sodium pentobarbitol and injected intravenously with glucose (1 g/kg body wt in a 50% wt/vol solution). Six rats from each treatment were killed by exsanguination at 0, 30, 60 and 120 minutes after glucose injection. Liver copper was measured by atomic absorption spectrophotometry. Reduction in liver copper content and elevation in heart weight confirmed that the rats fed the test diet were copper-deficient. Plasma glucose levels in copper-deficient rats were significantly higher at 30 and 60 minutes compared to controls. After 2 hours there were no significant differences between treatments. Plasma insulin levels measured by radioimmunoassay were significantly lower at 30 minutes, but higher at 60 and 120 minutes in rats fed the test diet as compared to controls. It would thus appear likely that copper deficiency interferes with normal glucose utilization.

Function of pituitary-thyroid axis in copper-deficient rats.

Thirty male weanling Sprague-Dawley rats were fed either a copper deficient diet (0.85 mg Cu/kg) or a copper-adequate diet (8 mg Cu/kg). After 7 weeks, the rats were fasted for 12 hours, and injected intravenously with thyrotropin-releasing hormone (TRH, 30 ng/100 g body weight). Six rats from each treatment were killed at 0, 0.5, 1, 2 and 4 hours after TRH injection. Sera obtained at 0, 0.5 and 1 hour, and at 0.2 and 4 hours were used for the radioimmunoassay of thyroid-stimulating hormone (TSH) and thyroxine (T4), respectively. Reduction in liver copper content confirmed that the rats fed the test diet were copper-deficient. Serum TSH levels appeared to have peaked at 30 minutes but declined to a level higher than basal at 1 hour. No difference in TSH response was observed between the 2 treatments. Serum T4 response to TRH was reduced in the copper-deficient as compared to the adequate rats at all time intervals. After 2 hours a slight elevation was observed in the controls, but marked elevations in T4 were observed in both treatments at 4 hours. This reduction in T4 levels could be due to an impaired T4 synthesis or release in copper-deficient rats.