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Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

589 records · Page 33Linked to original sources
PubMedDate not supplied

Technical aspects of plasma leakage prevention in microporous capillary membrane oxygenators.

A limiting factor in using microporous capillary membrane oxygenators (CMO) for long-term extracorporeal lung support is leakage. Application of heparin-coated CMO requires additional examination because leakage is probably caused by the temperature conditions of the gas, the blood and the circuit environment, and the surface tension phenomenon at the micropores. The authors designed a thermostatized box in which the temperature of flowing gas (Tg) and blood (Tb), and the interior temperature of the box (Ti) could be regulated independently. Tb was adjusted to the animal's body temperature, and Tg was kept about 2 degrees C higher to prevent condensation of the evaporated fluid from the blood side, through the micropores, into the gas phase. Ti was maintained between Tg and Tb. The saturated outlet gas could therefore condense only outside the box. This system was used during 5 days of venovenous bypass using a covalently heparin-bonded (Carmeda) CMO (Maxima, Medtronic) in four adult sheep. No plasma leakage occurred, the surface tension of condensate water remained constant, and the gas exchange capacity of CMO was unchanged.

Animals↗
PubMedDate not supplied

Effects of the optical isomers of D 600 on cardiovascular parameters and on arrhythmias caused by aconitine and coronary artery ligation in anesthetized rats.

We examined the effects of the optical isomers of D 600 on cardiovascular parameters and on arrhythmias caused by aconitine infusion and ligation of left coronary artery in urethane-anesthetized rats. (-)-D 600 decreased blood pressure and LV dP/dtmax with respective Ed30% of 0.045 and 0.018 mg/kg i.v.; increased PQ duration with an ED20% of 0.045 mg/kg i.v.: and caused AV-block with an ED50 of 0.07 mg/kg i.v., thereby showing a potency 20--50 times that of (+)-D 600 and about twice that of the racemate. (+)-D 600 in the effective dose range additionally widened QRS complex (ED20%, 2.44 mg/kg i.v.) and increased arrhythmogenic aconitine dose (ED75% 4.97 mg/kg i.v.) with a potency about equal to quinidine. In contrast to the (-)-isomer and the racemate of D 600 and to (+/-)-verapamil, (+)-D 600, at a dose slightly below AV block-generating ED50 of 2.15 mg/kg i.v., significantly attenuated ventricular arrhythmias following left coronary artery ligation with a potency similar to 4.64 mg/kg i.v. quinidine but inferior to 4.64 mg/kg i.v. lidocaine. It is concluded that the optical isomers of D 600 exert stereospecific actions in vivo with respect to Ca2+-antagonistic potency. While (-)-D 600 in the effective dose range shows cardiovascular actions indicative of pure Ca2+-antagonistic properties, and activity of the racemate resides in the Ca2+-antagonistic properties of the (-)-isomer, cardiovascular effects of (+)-D 600 and its effectiveness against ventricular arrhythmias are indicative of parallel Ca2+-antagonistic and membrane-stabilizing properties.

Aconitine↗
PubMedDate not supplied

Studies on proteins identical to male and female genital tract secretions.

Rabbit seminal plasma and rabbit uterine fluid six days post coitum were used for disc-electrophoretical and immunological studies. With an antiserum, that was partially neutralized with normal rabbit serum and the uterine fluid, in the seminal plasma four groups of antigens could be demonstrated: antigens of type E, occurring in the seminal plasma only, antigens of type EU, occurring in the seminal plasma and the uterine fluid, antigens of type ES, occurring in the seminal plasma and the serum, and antigens of type EUS, occurring in the seminal plasma, the uterine fluid and the serum. Special consideration of the EU-antigen group exhibited five proteins: with biochemical methods four of them could be identified as uteroglobin, seminal plasma acid glycoprotein, a proteinase, and an alkaline phosphatase.

Alkaline Phosphatase↗
PubMedDate not supplied

Genital tract proteins in the male rabbit: I. Localization of uteroglobin.

Uteroglobin synthesis in reproductive and non-reproductive tissues of male and female rabbit was screened by means of double-diffusion tests and immunohistochemical studies. Immunoprecipitates were observed when homogenates of male accessory were incubated with a monospecific antiserum against uteroglobin; in the female the antigen occurred in the uterine secretion and in homogenates of the oviduct, six days post coitum. In nonreproductive tissue, the antigen appeared both in the male and in the female, in the homogenate of trachea and lung. The immunofluorescence technique exhibited the paraprostate gland as the site of synthesis of uteroglobin in the male genital tract. Moreover, the distribution of the fluorescence within the cells was identical to the distribution observed in the female genital tract.

Animals↗
PubMedDate not supplied

Genital tract proteins in the male rabbit: II. Alkaline phosphatase--enzyme action and site of synthesis.

An alkaline phosphatase was isolated from rabbit seminal plasma by ion-exchange chromatography, gel-filtration and preparative isoelectric focusing. Enzyme inhibition with Na2-EDTA was mostly effectively reverted by means of Mg2+, Zn2+ and Ca2+ in the incubation medium. The use of a monospecific antiserum against the seminal plasma alkaline phosphates permitted to identify through immunofluoresceine the ductus epididymis, deferens and its ampullae as the main site of synthesis of this protein.

Alkaline Phosphatase↗
PubMedDate not supplied

An evaluation of FASTMAP with emphasis on fine-mapping.

We present an evaluation of the FASTMAP method with special reference to the issue of fine-mapping, using both 'real-life' and constructed data, and demonstrate some of the shortcomings of the method. Since the advantages of FASTMAP in terms of savings in computer resources compared to LINK-MAP are enormous, further improvements of the FASTMAP method would be highly desirable.

Chromosome Mapping↗
PubMedDate not supplied

Second-line treatment with high-dose 5-fluorouracil and folinic acid in advanced colorectal cancer refractory to standard-dose 5-fluorouracil treatment.

Results with second-line treatment of advanced colorectal cancer are poor. Preliminary phase I/II results suggest encouraging response rates to high-dose 5-fluorouracil (FU) (2,600 mg/m2) combined with folinic acid (FA) in pretreated patients with advanced colorectal cancer. To determine the significance of weekly high-dose FU/FA in colorectal cancer refractory to weekly standard doses of FU/FA, a phase II study was initiated. 69 patients with metastatic colorectal cancer refractory to first-line weekly standard-dose FU/FA were treated with weekly high-dose FU 2,600 mg/m2 combined with FA 500 mg/m2 as a 2-hour infusion prior to FU application. Pretreatment was highly homogenous and consisted of weekly FU 500 mg/m2 combined with FA 500 mg/m2 or FA 20 mg/m2 or the pure stereoisomer of FA (6S-FA) 250 mg/m2. At the time of disease progression under first-line therapy, patients were transferred to high-dose FU/FA within 4 weeks. Treatment was continued until tumor progression under therapy was documented. Of the 69 evaluable patients, 17 (24.6%) achieved partial response (PR), 42 (60.9%) had no change (NC) and 10 (14.5%) had progressive disease under therapy. The median duration of PR was 7 months, the median time to progression of NC was 4 months. Median survival of all patients was 9 months, of patients with PR, 11.5 months. 33/38 patients with tumor-related pain experienced impressive relief under therapy. Prognostic factors for a beneficial outcome were complete response/PR under first-line therapy, a small number of metastatic sites and a good Karnofsky performance status. Moderate toxicity was observed, and the pattern of toxic events and severity did not differ from standard-dose FU regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Pharmacology of thromboxane A2, prostacyclin and other eicosanoids in the cardiovascular system.

The eicosanoids, a group of endogenous metabolites of the cell membrane phospholipid-derived fatty acid arachidonic acid (AA), are formed from AA via three main enzymatic pathways (cyclooxygenase, lipoxygenase, cytochrome P450) and include the classical prostaglandins (PGF2 alpha, E2, D2), TxA2, PGI2, the leukotrienes and HETEs/HPETEs, the lipoxins and various epoxy metabolites. In the cardiovascular system the current interest is focussed on TxA2 and PGI2. TxA2 is released from activated platelets, shows potent platelet aggregating and vasoconstricting properties and is therefore considered to be important in thrombotic and ischaemic diseases. Therapeutic strategies directed at interfering with endogenous TxA2 include inhibition of synthesis (aspirin, selective TxA2 synthase inhibitors) and, more recently, specific blockade of TxA2 receptors. PGI2 is released mainly from the vascular intima, potently inhibits platelet aggregation and shows vasodilator and cytoprotective properties. PGI2 and chemically stable PGI2-derivatives have been shown to be effective in the treatment of severe peripheral ischaemic diseases and offer further interesting prospectives like prevention of vascular reocclusion in bypass surgery and balloon catheter angioplasty as well as organ preservation in transplant surgery. Other eicosanoids like PGD2 and the leukotrienes may also be important mediators in cardiovascular disease. Whether they represent targets for innovative drug therapy in cardiovascular disease remains to be investigated.

Cardiovascular System↗
PubMedDate not supplied

Neuraminidase antibodies in serum and nasal washings after immunization by means of live and killed whole virion, split virion and subunit (HA and N) influenza vaccines.

Anti-neuraminidase antibody (ANAB) formation was determined in serum and nasal washing fluids pre- and post-vaccination in 278 adult healthy volunteers vaccinated with different types of current experimental and conventional influenza vaccines. The best systemic ANAB formation expressed as conversion rate (CR) was observed with the subunit vaccine "Sandovac" (CR = 90%) followed by the split virion vaccine "Begrivac S" (CR = 66%), the whole virion vaccine "Alorbat" (CR = 65%) and the live attenuated vaccine "Alice" (CR = 58%). The best local ANAB formation was obtained with live attenuated vaccines (CR = 47-50%) followed by "Begrivac S" (CR = 34%) and "Alorbat" (CR = 17%). The subunit vaccine, unfortunately, could not be tested for ANAB formation. On the basis of this data the optimal method of immunization against influenza would consist of simultaneous topical and parenteral application of live attenuated and inactivated subunit or split vaccine.

Administration, Intranasal↗
PubMedDate not supplied

[Early attachment experiences and behavioral problems in young children in a social and cognitive test situation].

In this article, the influence of quality of attachment (Ainsworth Strange Situation at 21 months) and of the intensity of attachment insecurity on test performance and emotional state in the test situation (Bayley-test at 20 months) are analyzed. The quality of attachment of 75 infants was classified according to Crittenden's PAA (Preschool Assessment of Attachment) as: secure (B), insecure defended (A) and insecure-coercive (C). Alternately, the infants were classified according to their intensity of insecurity of attachment across subtypes of qualities (secure, insecure, highly insecure). Securely attached (B) infants had the best Bayley Mental scores, were socially open and bodily relaxed. The insecure-defended (A) infants had moderate test results, were moderately open and tense, whereas the insecure-coercive (C) infants showed not only the worst test-results but were often withdrawn, fearful, tense, and poorly coordinated. Additional clinical signs of disorganization were spread unspecifically over all attachment groups particularly those of the insecure children. In the classification of children according to intensity of insecurity, these signs of disorganization accumulated particularly in the group of highly insecure infants. Children with highly insecure attachment who also exhibited unusual test situation behavior also had the lowest Bayley-test scores in the Mental Scale. These results are interpreted in the sense of balance between test engagement and emotional cost.

Arousal↗
PubMedDate not supplied

Design, synthesis and characterization of bradykinin antagonists via cyclization of the modified backbone.

With the aim of synthesizing cyclic antagonists of the nonapeptide hormone bradykinin with minimal side chain modification, we performed backbone to backbone and backbone to side chain cyclization. To probe and compare different strategies for this new kind of cyclization, the branched peptide bonds were formed by both reductive alkylation on the solid phase and by using preformed building units. Lactam bridges between the modified amide groups were formed by the use of the phenylalanine derivatives N(CH2COOH)Phe and N(CH2CH2NH2)Phe. The best results in the formation of the N-alkylamide bond were obtained with the coupling reagent PyBrop. The coupling rate was monitored by estimation of the N-terminal Fmoc-group. The cyclization was performed on the solid support. Unexpected difficulties resulted from the instability of the N-alkylamide bond under strong acidic conditions, as used for deprotection and for removal from the resin. We synthesized peptides with backbone to backbone cyclization between positions 2 and 5, as well as backbone to side chain cyclizations between positions 0 and 5, and between 2 and 6. The relatively high biological activities of some of the cyclic analogues support the supposed receptor-bound conformation of bradykinin antagonists with a beta-turn in the N-terminal sequence.

Animals↗