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Biomedical subjects

N Weber

Publications and source records attributed to N Weber.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Controlled inhalation of beta2-sympaticomimetica after bronchial provocation].

The results of several studies indicate that controlling the breathing pattern (inhaled volume and flow rate) during inhalation increases the efficacy of drug delivery to the lungs. By inhaling slowly, deeply and under controlled conditions, intrapulmonary deposition of aerosol and its reproducibility can be increased. However, it has not yet been proven that such inhalations are well tolerated by patients, especially those with airway obstructions. In this study 12 patients with mild asthma underwent a bronchial provocation test. The following broncholysis was performed with controlled, slow, and deep inhalation using the AKITA-device. The patients were asked about the convenience of this inhalation using a questionnaire. In 80 % the controlled inhalation was judged as convenient, neither as too slow nor as too fast, neither as too deep nor as too shallow. Thus it turned out that controlled deep and slow inhalations are convenient even for patients with mild airway obstruction.

Administration, Inhalation↗
PubMed2003

Peripheral deposition of alpha1-protease inhibitor using commercial inhalation devices.

Patients with hereditary alpha1-proteinase inhibitor (alpha1-PI) deficiency are at risk of developing lung emphysema. To prevent the development of this disease, alpha1-PI replacement therapy via inhalation may be a more convenient and effective therapy than the intravenous administration of the drug. In order to optimise this treatment approach, lung deposition of inhaled radiolabelled alpha1-PI (Prolastin) was studied using four different commercial inhalation devices (PARI-LC Star, HaloLite, and AKITA system in combination with LC Star and Sidestream) in six patients with alpha1-PI deficiency and mild-to-severe chronic obstructive pulmonary disease. The time required to deposit 50 mg of the Prolastin (5% solution) in the lung periphery was used as a measure for the efficiency of delivery. The time was calculated from measurements of total and peripheral lung deposition of the radiolabelled alpha1-PI. This time was shortest for the AKITA system (18-24 min) and significantly higher for the PARI-LC Star (44 min) and the HaloLite (100 min). The higher efficiency of drug delivery using the AKITA system is due to the fact that this device controls breathing patterns, which are optimised for each patient individually.

Administration, Inhalation↗
PubMed2001

Bethesda guidelines: relation to microsatellite instability and MLH1 promoter methylation in patients with colorectal cancer.

BACKGROUND: Microsatellite instability is a hallmark of mismatch repair deficiency in hereditary nonpolyposis colorectal cancer and results from mutations in the mismatch repair genes MLH1 or MSH2 or from gene inactivation associated with DNA methylation. The Bethesda guidelines were established to identify patients with colorectal cancer who should be tested for microsatellite instability. OBJECTIVE: To assess the Bethesda guidelines for detection of microsatellite instability and to determine the role of MLH1 promoter methylation in colorectal cancer. DESIGN: Prospective cohort study. SETTING: Tertiary care referral center in Frankfurt, Germany. PATIENTS: 125 consecutive patients with colorectal cancer. MEASUREMENTS: Patients were assessed according to the Bethesda guidelines, and tumor specimens were analyzed for microsatellite instability. Patients with microsatellite instability were tested for MLH1 promoter methylation and MLH1 and MSH2 germline mutations. RESULTS: Microsatellite instability was detected in 17 of 58 patients who fulfilled and 5 of 67 patients who did not fulfill criteria of the Bethesda guidelines. In 11 of 17 patients with microsatellite instability who fulfilled Bethesda guidelines, an MLH1 (n = 3), MSH2 (n = 7), or combined MLH1 and MSH2 (n = 1) mutation was found. Among the patients with microsatellite instability who did not fulfill Bethesda guidelines, no mutations were observed; MLH1 promoter methylation was observed in 6 of 11 patients with an MLH1 or MSH2 mutation and 5 of 11 patients without an MLH1 or MSH2 mutation. CONCLUSIONS: The Bethesda guidelines are useful for selecting patients for microsatellite instability testing. MLH1 and MSH2 testing should be recommended in all patients with colorectal cancer and microsatellite instability who fulfill at least one Bethesda criterion. MLH1 promoter methylation may accompany rather than initiate carcinogenesis in patients with colorectal cancer who have mismatch repair gene defects.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Gene monitoring of surface-activated monocytes in circulating whole blood using duplex RT-PCR.

Previous studies have shown that blood-contacting materials activate blood monocytes. The aim of this study is to evaluate a highly sensitive technique for detecting changes at the mRNA level in circulating monocytes and to find suitable "gene markers" for assessing the hemocompatibility of biomaterials. Human blood was recirculated in a modified Chandler Loop formed of test tubes. Five groups of biomaterials were compared. Monocytes were separated by using magnetic beads, and gene expression analyses were performed using RT-PCR. We investigated the mRNA expression of stress proteins (hsp70) and inflammatory markers (IL-1alpha, IL-1beta, IL-6, TNF-alpha). mRNAs for cytokines were highly upregulated in LPS-stimulated monocytes. Hsp70 transcripts were upregulated after heat shock but were not influenced by treatment with LPS. The gene expression of the cytokines was affected by various biomaterials. The intensity of the inflammatory response increased in the following order: heparin coatings (PVC) < uncoated PVC < silicone, polypeptide-coated PVC. No change was seen in the expression of the hsp70 genes. An inhibitory effect of systemic heparin on surface-activated monocytes was observed for the mRNA expression of the cytokines. The recirculation of human blood in an in vitro model in combination with the immunomagnetic separation of monocytes and the Duplex RT-PCR method is a powerful tool for getting reliable results. Our data demonstrate that hsp70 genes cannot be recommended for short-term, biomaterial-induced mRNA expression studies. Conversely, mRNAs for IL-1alpha, IL-1beta, IL-6, and TNF-alpha were expressed in a material-dependent manner. Thus our model provides an effective tool for assessing the hemocompatibility of biomaterials before their clinical application and it also can serve as a safety control during the industrial manufacturing process. This method can be applied to various blood cell populations and numerous gene expression studies and may enable a more fundamental understanding of the biologic processes involved in blood-material interactions.

Biocompatible Materials↗
PubMed2001

Increased sputum IL-8 and IL-5 in asymptomatic nonspecific airway hyperresponsiveness.

Since asymptomatic, nonspecific airway hyperresponsiveness (BHR) may be due to an enhanced local inflammatory response, we studied molecular markers of inflammation in induced sputum from subjects with asymptomatic BHR (n = 14) compared with control subjects (n = 13) and patients with chronic obstructive pulmonary disease (COPD) (n = 10). Pulmonary lung function parameters were measured by spirometry and body plethysmography. Hyperresponsiveness was defined based on histamine challenge. Induced sputum samples were collected and the solid phase was isolated and analyzed for leukocyte numbers and differential and for cytokines (ELISA). IL-8 was 2.4-fold increased (p = 0.036) in the sputum of subjects with asymptomatic BHR (24.8 +/- 22.0 ng/mL; +/- SD) and 11.2-fold enhanced in patients with COPD (117.8 +/- 106.3 ng/mL) as compared with control subjects (10.5 +/- 7.7 ng/mL). In control subjects, no IL-5 was measured, however, sputum of those with asymptomatic BHR contained IL-5 at 0.044 +/- 0.090 ng/mL fluid and COPD patients at 1.00 +/- 2.01 ng/mL. GM-CSF could not be detected in sputum samples of any subjects investigated. Number of total leukocytes was higher in those with asymptomatic BHR and COPD (with BHR: 9.4 +/- 10.8 x 10(5); COPD: 83.5 +/- 182.5 x 10(5)) compared with persons without BHR (2.9 +/- 3.4 x 10(5)). PMN were increased in patients with asymptomatic BHR (4.1 +/- 5.3 x 10(5)) (38.8 +/- 24.7%) and COPD (32.9 +/- 71.0 x 10(5)) (75.4 +/- 18.6%) compared with controls (0.7 +/- 0.9 x 10(5)) (25.8 +/- 25.7%). In contrast to PMN counts in those with asymptomatic BHR (0.06 +/- 0.11 x 10(5)) (1.5 +/- 3.7%), eosinophil counts were only slightly increased compared with control subjects (0.01 +/- 0.02 x 10(5)) (0.6 +/- 0.9%). This study supports the hypothesis that BHR in asymptomatic people is associated with airway inflammation that may predispose to development of chronic diseases such as COPD.

Adult↗
PubMed2001

In vitro test for the effectiveness of antioxidants as inhibitors of thiyl radical-induced reactions with unsaturated fatty acids.

Attacks of thiyl radicals on the double bonds of unsaturated fatty acids lead to stereomutation (cis-, trans-isomerization without double-bond migration) and addition reactions (thioether formation). On the basis of these findings, an in vitro test system has been developed which allows the study of the effectiveness of specific antioxidants in preventing thiyl radical-induced attacks on unsaturated fatty acids. The test involves thermal treatment of a mixture of oleic (cis-9-octadecenoic) acid and 1-tetradecanethiol with the antioxidant, followed by measurement of the extent of formation of the products of stereomutation and addition (i.e., elaidic (trans-9-octadecenoic) acid and isomeric 9(10)-S-tetradecylstearic acids, respectively) by gas chromatography of their methyl esters as a function of antioxidant concentration. Antioxidants such as octyl gallate, ascorbic acid 6-O-palmitate, ubiquinone 50 (coenzyme Q(10)), rac-alpha-tocopherol, and 2,6-di-tert-butyl-4-methylphenol (BHT) were tested for their ability to protect the >C=C< double bond of oleic acid against attacks of thiyl radicals generated from 1-tetradecanethiol by heating. The results show that octyl gallate, ascorbic acid 6-O-palmitate and, to some extent, ubiquinone 50 (coenzyme Q(10)) were highly effective in preventing reactions of free thiyl radicals with oleic acid, whereas rac-alpha-tocopherol and BHT were moderately effective.

Antioxidants↗
PubMed2001

Fatty acid steryl, stanyl, and steroid esters by esterification and transesterification in vacuo using Candida rugosa lipase as catalyst.

Sterols (sitosterol, cholesterol, stigmasterol, ergosterol, and 7-dehydrocholesterol) and sitostanol have been converted in high to near-quantitative yields to the corresponding long-chain acyl esters via esterification with fatty acids or transesterification with methyl esters of fatty acids or triacylglycerols using lipase from Candida rugosa as biocatalyst in vacuo (20-40 mbar) at 40 degrees C. Neither organic solvent nor water is added in these reactions. Under similar conditions, cholesterol has been converted to cholesteryl butyrate and steroids (5alpha-pregnan-3beta-ol-20-one or 5-pregnen-3beta-ol-20-one) have been converted to their propionic acid esters, both in moderate to high yields, via transesterification with tributyrin and tripropionin, respectively. Reaction parameters studied in esterification include the temperature and the molar ratio of the substrates as well as the amount and reuse properties of the C. rugosa lipase. Lipases from porcine pancreas, Rhizopus arrhizus, and Chromobacterium viscosum are quite ineffective as biocatalysts for the esterification of cholesterol with oleic acid under the above conditions.

Candida↗
PubMed2001

Steryl and stanyl esters of fatty acids by solvent-free esterification and transesterification in vacuo using lipases from Rhizomucor miehei, Candida antarctica, and Carica papaya.

Sitostanol has been converted in high to near-quantitative extent to the corresponding long-chain acyl esters via esterification with oleic acid or transesterification with methyl oleate or trioleoylglycerol using immobilized lipases from Rhizomucor miehei (Lipozyme IM) and Candida antarctica (lipase B, Novozym 435) as biocatalysts in vacuo (20-40 mbar) at 80 degrees C, whereas the conversion was markedly lower at 60 and 40 degrees C. Corresponding conversions observed with papaya (Carica papaya) latex lipase were generally lower. High conversion rates observed in transesterification of sitostanol with methyl oleate at 80 degrees C using Lipozyme IM were retained even after 10 repeated uses of the biocatalyst. Saturated sterols such as sitostanol and 5alpha-cholestan-3beta-ol were the preferred substrates as compared to Delta(5)-unsaturated cholesterol in transesterification reactions with methyl oleate using Lipozyme IM. Transesterification of cholesterol with dimethyl 1,8-octanedioate using Lipozyme IM in vacuo yielded methylcholesteryl 1,8-octanedioate (75%) and dicholesteryl 1,8-octanedioate (5%). However, transesterification of cholesterol with diethyl carbonate and that of oleyl alcohol with ethylcholesteryl carbonate, both catalyzed by Lipozyme IM, gave ethylcholesteryl carbonate and oleylcholesteryl carbonate, respectively, in low yield (20%). Moreover, cholesterol was transesterified with ethyl dihydrocinnamate using Lipozyme IM to give cholesteryl dihydrocinnamate in moderate yield (56%), whereas the corresponding reaction of lanosterol gave lanosteryl oleate in low yield (14%).

Candida↗
PubMed2001

Oxygenator thrombosis: worst case after development of an abnormal pressure gradient--incidence and pathway.

The development of an abnormally high pressure gradient (APG) before the membrane oxygenator (MO) is a complication that occurs during some extracorporeal circulation (ECC) procedures. The present study deals with the incidence of an APG and discusses a probable causative pathway by comparing surface-coated and uncoated oxygenation systems. Five thousand six hundred and seventeen adult ECCs were carried out (2,581 without and 3,036 with surface coatings). The incidence of an APG, therefore, amounted to 0.03% in the group with coated systems and 4.3% in the uncoated group. In addition, an in vitro study demonstrated significantly reduced adhesion and activation of platelets and leucocytes when the surfaces of the MOs were coated with heparin or polypeptides. The advantages of coating surfaces of ECC devices possibly depend on the selective adsorption of particular plasma proteins. These will presumably form a biocompatible membrane on the surface, and minimize pathological deposit of fibrin, platelets and other blood cells, and, therefore, implicate the prevention of an oxygenator failure.

Blood Platelets↗
PubMed2000

Adaptation to the edge of chaos in the self-adjusting logistic map.

Self-adjusting, or adaptive, systems have gathered much recent interest. We present a model for self-adjusting systems which treats the control parameters of the system as slowly varying, rather than constant. The dynamics of these parameters is governed by a low-pass filtered feedback from the dynamical variables of the system. We apply this model to the logistic map and examine the behavior of the control parameter. We find that the parameter leaves the chaotic regime. We observe a high probability of finding the parameter at the boundary between periodicity and chaos. We therefore find that this system exhibits adaptation to the edge of chaos.

Adaptation, Biological↗
PubMed2000

Simultaneous derivatization of acyl and S-alkyl moieties of acyl thioesters by using trimethylsulfonium hydroxide for gas chromatographic analysis.

The reaction of long-chain acyl thioesters, viz. lauric acid dodecyl thioester, 1,8-di-S-palmitoyl octanedithiol, and tristearoyl alpha-monothioglycerol, with trimethylsulfonium hydroxide in the presence of methanol leads to simultaneous derivatization of acyl moieties and S-alkyl moieties of acyl thioesters to the corresponding fatty acid methyl esters and methyl alkylsulfides, respectively. These derivatized products were analyzed by gas chromatographic technique.

Chromatography, Gas↗
PubMed2000

Antioxidants eliminate stereomutation and thioether formation during lipase-catalyzed thioesterification and transthioesterification for the preparation of uniform cis- and trans-unsaturated thioesters.

The lipase-catalyzed preparation of acyl thioesters from unsaturated fatty acids and alkanethiols is accompanied by the formation of geometrical isomers via stereomutation and of thioether derivatives via addition at the olefinic bond, both induced by thiyl radicals. Therefore, a method was developed in order to inhibit radical generation by the addition of antioxidants and thus prevent the formation of geometrical isomers and thioether derivatives during the lipase-catalyzed preparation of unsaturated acyl thioesters. In the presence of antioxidants such as 2,6-di-t-butyl-4-methylphenol (BHT) and octyl gallate thioesterification of oleic and elaidic acids with 1-tetradecanethiol as well as transthioesterification of methyl linoleate with 1-tetradecanethiol led to the corresponding geometrically uniform thioesters without radical-induced side reactions. In the absence of antioxidants rapid stereomutation of unsaturated acyl moieties as well as formation of high proportions of thiyl radical-induced addition products such as isomeric 9(10)-S-tetradecyl stearic acids and 9(10)-S-tetradecyl stearic acid tetradecyl thioesters were observed.

Antioxidants↗
PubMed2000

Response to criticisms of the US FDA parametric approach for withdrawal time estimation: rebuttal and comparison to the nonparametric method proposed by Concordet and Toutain.

The benefits and drawbacks of using nonparametric methods for estimating product withdrawal times have been debated for many years. This issue was recently revived by Concordet & Toutain (1997a, b) when they described a nonparametric method for withdrawal time estimation. The authors urged the international adoption of this approach, basing their recommendation on three fundamental concerns: (1) the lack of a consistent official procedure for determining a withdrawal time within the European Union (EU); (2) the need to identify a statistical method for improving the international harmonization of withdrawal times for new chemical entities; and (3) a lack of confidence in the robustness of the US Food and Drug Administration/Center for Veterinary Medicine (US FDA) procedure, particularly with respect to minor violations in the underlying parametric assumptions. Due to the critical nature of these issues, the US FDA considers it vital to respond to these concerns. This paper provides a description of the US FDA parametric procedure. We also examine the statistical concerns expressed by Concordet and Toutain, identifying the reasons for our confidence in the US FDA parametric approach. Finally, using their Monte Carlo simulation models, we generate additional datasets to explore the behaviour of their nonparametric procedure and evaluate its ability to support US FDA regulatory activities.

Animal Diseases↗
PubMed2000

Quality assessment of heparin coatings by their binding capacities of coagulation and complement enzymes.

In vitro testing of blood contacting materials before clinical application is generally advisable. Four heparin coatings from different manufacturers were tested for adsorbed proteins and soluble activation markers. The surface with the highest antithrombin, thrombin, high-molecular-weight-kininogen (HMWK) and the lowest fibrinogen binding capacity (Carmeda, Medtronic) showed significantly lower levels of granulocytes and platelet activation (beta-TG, PMN-elastase release). No statistically significant differences in soluble markers of the coagulation system could be detected (F1 + 2, TAT). Interestingly, complement activation (TCC) was significantly reduced within the group of the lowest adsorption of the complement factor C3. Our data demonstrate that there is a relation between the binding affinity of proteins (C1-inhibitor, C3-complement) and the consecutive changes in complement activation (TCC). Therefore, measuring adsorbed proteins on artificial surfaces is a suitable, sensitive and very reproducible method for assessing the thrombogenicity of biomaterials.

Adsorption↗
PubMed2000

An empirical test of a self-care model of women's responses to battering.

A model of women's responses to battering was constructed based on Orem's theory of self-care deficit and on empirical and clinical observations. The model proposed that the age, educational level, and cultural influences as basic conditioning factors would all be directly related to relational conflict, which would be negatively related to self-care agency (as a mediator) and indirectly related to both outcomes of health and well-being. Using simultaneous structural equation modeling with specification searching, a modified model was derived that eliminated the mediation path but supported direct effects of both abuse and self-care agency on health. The derived model was found to be only a borderline fit with the data, probably due to measurement problems, lack of inclusion of important variables, and small sample size (N = 117). However, there was support for several of the relationships deduced from and/or congruent with Orem's theory.

Adaptation, Psychological↗
PubMed2000

[Comparative studies of the adsorption behavior of plasma proteins to heparin-coated surfaces].

Over the past 10 years, investigations have shown that heparin coating optimizes haemocompatibility in extracorporeal circulation systems. To date, however, the mechanisms involved have not been identified. 20 ml of fresh human blood were circulated in an in vitro closed-loop model with and without heparin coating. Using a newly developed ELISA, a quantitative analysis of the adsorbed plasma proteins was done. In addition, changes in coagulation, complement and blood cell releasing factors were measured by ELISA methods: prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin-III complex (TAT), PMN-elastase, beta-thromboglobulin (beta-TG) and terminal complement-complex (TCC). In uncoated tubing, high concentrations of fibrinogen, fibronectin, prothrombin, vitronectin, alpha 2-macroglobulin, von Willebrand factor and complement factor C3 were found. Large amounts of antithrombin-III, HMWK and C1-esterase inhibitor were found on the heparinized surfaces. In addition, the concentrations of the soluble plasma protein markers F1 + 2, FPA, PMN-elastase, TCC and beta-TG were significantly lower (p < 0.05) in the presence of heparin coating. The haemocompatibility of "foreign" surfaces depends largely on the extent to which the processes of activation and inhibition of humoral and cellular mediators permanently occurring at the natural endothelium can be simulated. Owing to the low adsorption of procoagulatory and proinflammatory enzymes, heparin-coated surfaces demonstrate significantly improved haemocompatibility.

Adsorption↗