Search PubMed⌕ Search

Biomedical subjects

G Wagner

Publications and source records attributed to G Wagner.

At least 91 records · Page 5Linked to original sources
PubMed2000

[Semi-invasive cardiac output measurement using a combined transesophageal ultrasound device. Early experiences].

OBJECTIVE: Measurement of cardiac output (CO) with pulmonary artery catheter (PAC) is currently item of many discussions. We investigated the reliability of results using the noninvasive measurement of aortic blood flow (ABF) (combined Doppler- and M-Mode transesophageal ultrasound, Dynemo 3000, Sometec Inc, Paris, France). METHODS: In 75 patients during cardiac or major abdominal surgery we performed 313 simultaneous measurements of CO and ABF. RESULTS: Placement of ultrasound probe into correct position took less than 2 min. Quality and stability of ultrasound signals were good. The coefficient of correlation between ABF and CO was found to be 0.89 with CO = 0.97 x ABF + 1.1, Bland-Altman-Test positive. CONCLUSION: Results of ABF detected by combined Doppler- and M-Mode-Echography are comparable with results of CO obtained by PAC. Therefore we are convinced that this noninvasive method will find its place in clinical situations of compromised CO.

Abdomen↗
PubMed2000

Aberrant right pulmonary artery and double outlet ventricle: one-stage repair.

We report a 13-month-old male child with anomalous origin of the right pulmonary artery from the ascending aorta and a double outlet right ventricle. Aortic wall was used for elongation of the pulmonary artery and side-to-end connection to the pulmonary trunk. Special emphasis is made on this particular operative technique for strictly laterally originating right pulmonary artery that requires no prosthetic material, avoids extreme stretching, and may enable normal growth potential.

Aorta↗
PubMed2000

Temporal evolution of traditional versus transformed ECG-based indexes in patients with induced myocardial ischemia.

The time course of changes in the electrocardiogram as a result of myocardial ischemia induced during prolonged coronary angioplasty has been studied. We have analyzed the electrocardiogram evolution during the occlusion in terms of the Ischemic Changes Sensor, which is a parameter that describes the capacity of different indexes to detect induced changes. Traditional indexes at specific time locations (ST level, T wave amplitude and position, and durations of QT interval and QRS complex) and global indexes (based on the Karhunen-Loève transform as applied to the QRS complex, ST-T complex, ST segment and T wave) have been considered. The global indexes better detected ischemic changes than the traditional indexes. The most sensitive were the index for the ST-T complex (89%) in the Karhunen-Loève transform-derived group and for the ST level (61%) in the traditional group. Changes in the ventricular repolarization period usually appeared earlier (77% of patients) than changes in the depolarization period (23% of patients). A similar percentage of patients exhibited the earliest ischemic changes in the T wave (41%) and in the ST segment (36%). The evolution of the Ischemic Changes Sensor parameters showed that the majority (60%) of the total changes occurred during the first minute of occlusion. The results suggest that the use of global electrocardiogram indexes better reflect ischemic changes than do traditional indexes, such as the ST segment deviation.

Angioplasty, Balloon, Coronary↗
PubMed2000

Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy.

This investigation of fluvoxamine and fluoxetine-norfluoxetine distributions in vivo at steady-state and of quantitative kinetics in brain and plasma after drug therapy interruption was performed by fluorine nuclear magnetic resonance spectroscopy (19F MRS), spectroscopic imaging (MRSI), and plasma HPLC on 12 subjects treated for depression. MRSI suggests a homogeneous distribution of 19F MRS visible fluvoxamine mainly in brain. Fluvoxamine steady-state brain concentrations (12 +/- 5 microM; n = 13) and brain-to-plasma concentration ratios (10 +/- 2; n = 12) were similar to those of combined fluoxetine-norfluoxetine (CF-norfluoxetine) (13 +/- 6 microM; n = 4 and 10 +/- 6; n = 4). Fluvoxamine brain elimination half-life (79 +/- 24 hours; n = 4) was significantly shorter than that of CF-norfluoxetine (382 +/- 48 hours; n = 2). Fluvoxamine brain-to-plasma-half-life-ratio was 2.2 +/- 0.3 (n = 4), contrarily to CF-norfluoxetine (1.0 +/- 0.3; n = 2). This study shows that quantitative pharmacokinetics in target organs by 19F MRS in vivo should prove useful for understanding and investigating outcome of treatment modifications and side effects.

Adult↗
PubMed2000

The eIF1A solution structure reveals a large RNA-binding surface important for scanning function.

The translation initiation factor eIF1A is necessary for directing the 43S preinitiation complex from the 5' end of the mRNA to the initiation codon in a process termed scanning. We have determined the solution structure of human eIF1A, which reveals an oligonucleotide-binding (OB) fold and an additional domain. NMR titration experiments showed that eIF1A binds single-stranded RNA oligonucleotides in a site-specific, but non-sequence-specific manner, hinting at an mRNA interaction rather than specific rRNA or tRNA binding. The RNA binding surface extends over a large area covering the canonical OB fold binding site as well as a groove leading to the second domain. Site-directed mutations at multiple positions along the RNA-binding surface were defective in the ability to properly assemble preinitiation complexes at the AUG codon in vitro.

Amino Acid Sequence↗
PubMed2000

Structure of the Mad2 spindle assembly checkpoint protein and its interaction with Cdc20.

The checkpoint protein Mad2 inhibits the activity of the anaphase promoting complex by sequestering Cdc20 until all chromosomes are aligned at the metaphase plate. We report the solution structure of human Mad2 and its interaction with Cdc20. Mad2 possesses a novel three-layered alpha/beta fold with three alpha-helices packed between two beta-sheets. Using deletion mutants we identified the minimal Mad2-binding region of human Cdc20 as a 40-residue segment immediately N-terminal to the WD40 repeats. Mutagenesis and NMR titration experiments show that a C-terminal flexible region of Mad2 is required for binding to Cdc20. Mad2 and Cdc20 form a tight 1:1 heterodimeric complex in which the C-terminal segment of Mad2 becomes folded. These results provide the first structural insight into mechanisms of the spindle assembly checkpoint.

Amino Acid Sequence↗
PubMed2000

Impact of erectile dysfunction on quality of life: patient and partner perspectives.

Quality of life (QoL) has become one of the important parameters in the evaluation of treatment and assessment of medical conditions, and it may be an important tool in determining the urgency of the need for therapeutic intervention for erectile dysfunction (ED). It is important to evaluate QoL of the couple, because men and women alike will suffer because of male erectile disability. Future drug trials, as well as studies of sexological intervention programs, should involve both partners. International Journal of Impotence Research (2000) 12, Suppl 4, S144-S146.

Erectile Dysfunction↗
PubMed2000

Cultured human keratinocytes on type I collagen membranes to reconstitute the epidermis.

The development of new techniques and modifications to overcome some of the disadvantages in cultured keratinocyte grafting has been motivated by several well-known drawbacks in the use of cultured epithelial autografts such as long culture periods, lack of adherence, difficulty in handling, lack of dermal substrates, and high costs. Two recent insights have influenced further research. On the one hand, it has been shown that the use of undifferentiated proliferative cells in fibrin glue suspensions is effective in epithelial reconstitution. On the other hand, the enzymatic release of cells from the culture surfaces is a critical step leading to at least temporary destruction of anchoring structures of the cultured cells. In this study, we tried to combine these two aspects in an attempt to modify common modalities of keratinocyte transplantation. To avoid dispase dissolving of the cultured cells, keratinocytes were seeded onto bovine collagen type I membranes without feeder layers and under serum-free culture conditions. Subconfluent monolayers of cultured human keratinocytes were transplanted as an upside-down graft on collagen membranes (keratinocyte collagen membrane grafts [KCMG], n = 12) after 3 days of culture or as membrane grafts alone (n = 12) onto standard nude mice full-thickness wounds. Fully differentiated epidermis was found at 21 days after grafting KCMG with persistence of human keratinocytes. This study demonstrates that upside-down grafts of undifferentiated monolayers of keratinocytes on non-cross-linked bovine type I collagen membranes do lead to an early reconstitution of multilayered squamous epithelium with enhanced wound healing compared to the control group. The upside down KCMG grafting technique is able to transfer actively proliferative keratinocytes and simplifies the application compared to conventional epithelial sheet grafting.

Animals↗
PubMed2000

Recombinant decorsin: dynamics of the RGD recognition site.

Decorsin is an antagonist of integrin alphaIIbbeta3 and a potent platelet aggregation inhibitor. A synthetic gene encoding decorsin, originally isolated from the leech Macrobdella decora, was designed, constructed, and expressed in Escherichia coli. The synthetic gene was fused to the stII signal sequence and expressed under the transcriptional control of the E. coli alkaline phosphatase promoter. The protein was purified by size-exclusion filtration of the periplasmic contents followed by reversed-phase high-performance liquid chromatography. Purified recombinant decorsin was found to be indistinguishable from leech-derived decorsin based on amino acid composition, mass spectral analysis, and biological activity assays. Complete sequential assignments of 1H and proton bound 13C resonances were established. Stereospecific assignments of 21 of 25 nondegenerate b-methylene groups were determined. The RGD adhesion site recognized by integrin receptors was found at the apex of a most exposed hairpin loop. The dynamic behavior of decorsin was analyzed using several independent NMR parameters. Although the loop containing the RGD sequence is the most flexible one in decorsin, the conformation of the RGD site itself is more restricted than in other proteins with similar activities.

Amino Acid Sequence↗
PubMed2000

Adrenergic and cholinergic regulation of in vitro melatonin release during ontogeny in the pineal gland of Long Evans rats.

Melatonin, produced by the pineal gland, plays an important role in a great variety of neuroendocrine functions. The rhythmic release of melatonin by the mammalian pineal gland is regulated by norepinephrine (NE) acting via alpha- and beta-adrenergic receptors utilizing distinct signal transduction pathways. Acetylcholine has been demonstrated to exert various effects in the mammalian pineal gland, including an inhibitory action on the NE-induced stimulation of melatonin production. However, data obtained by different laboratories on the interaction of adrenergic receptors are not consistent and whether muscarinic and/or nicotinic receptors participate in the various effects of acetylcholine is still contradictory. To investigate noradrenergic as well as cholinergic mechanisms during ontogeny, we have investigated in vitro melatonin release from isolated pineal glands of Long Evans rats of different ages. NE as well as the beta-adrenergic receptor agonist isoproterenol (ISO) significantly elevated the melatonin release in pineal glands from postnatal week 2 on. In pineal glands originating from 2- to 4-week-old rats, simultaneous activation of alpha- and beta-adrenergic receptors by ISO and the alpha-adrenergic receptor agonist methoxamine (MET) or NE resulted in significantly weaker stimulation of melatonin production than beta-receptor activation alone. Acetylcholine evoked a significant increase in melatonin release in pineal glands from 2- to 4-week-old rats. In pineal glands from 8- to 20-week-old animals, ISO, ISO + MET or NE stimulated pineal melatonin release to comparable maxima, whereas acetylcholine was without effect. Our data indicate (1) that the adrenergic stimulation of pineal melatonin production in Long Evans rats is dominated by a beta-adrenergic mechanism, (2) that additional alpha-adrenergic receptor activation is inhibitory and (3) dependent on the developmental status of the animal, and (4) that acetylcholine acting via muscarinic receptors has the capacity to stimulate melatonin release during early ontogeny. These data suggest that the melatonin-generating system of the pineal gland of Long Evans rats undergoes substantial functional changes during early postnatal development, including adrenergic as well as cholinergic mechanisms.

Acetylcholine↗
PubMed2000

Report of the international consensus development conference on female sexual dysfunction: definitions and classifications.

PURPOSE: Female sexual dysfunction is highly prevalent but not well defined or understood. We evaluated and revised existing definitions and classifications of female sexual dysfunction. MATERIALS AND METHODS: An interdisciplinary consensus conference panel consisting of 19 experts in female sexual dysfunction selected from 5 countries was convened by the Sexual Function Health Council of the American Foundation for Urologic Disease. A modified Delphi method was used to develop consensus definitions and classifications, and build on the existing framework of the International Classification of Diseases-10 and DSM-IV: Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, which were limited to consideration of psychiatric disorders. RESULTS: Classifications were expanded to include psychogenic and organic causes of desire, arousal, orgasm and sexual pain disorders. An essential element of the new diagnostic system is the "personal distress" criterion. In particular, new definitions of sexual arousal and hypoactive sexual desire disorders were developed, and a new category of noncoital sexual pain disorder was added. In addition, a new subtyping system for clinical diagnosis was devised. Guidelines for clinical end points and outcomes were proposed, and important research goals and priorities were identified. CONCLUSIONS: We recommend use of the new female sexual dysfunction diagnostic and classification system based on physiological as well as psychological pathophysiologies, and a personal distress criterion for most diagnostic categories.

Female↗
PubMed2000

Abanoquil, a new alpha-1 adrenoceptor antagonist. In vitro and in vivo effect on erectile tissue.

Using an organ bath model with porcine cavernosal tissue strips and an in vivo monkey model we demonstrated that abanoquil, a novel alpha adrenoceptor antagonist, is able to relax contracted tissue strips and induce erectile response when injected intracorporally. The erectile response in the monkeys was not dose-related and compared to the effect of papaverine injections, abanoquil induced a lower level of tumescence and rigidity. Hence, abanoquil might be useful as a facilitator of erection in the pharmacological treatment of erectile dysfunction.

Adrenergic alpha-Antagonists↗
PubMed2000

Abanoquil, a new alpha-1 adrenoceptor antagonist. In vitro and in vivo effect on erectile tissue.

Using an organ bath model with porcine cavernosal tissue strips and an in vivo monkey model we demonstrated that abanoquil, a novel alpha adrenoceptor antagonist, is able to relax contracted tissue strips and induce erectile response when injected intracorporally. The erectile response in the monkeys was not dose-related and compared to the effect of papaverine injections, abanoquil induced a lower level of tumescence and rigidity. Hence, abanoquil might be useful as a facilitator of erection in the pharmacological treatment of erectile dysfunction. International Journal of Impotence Research (2000) 12, Suppl 1, S37-S40

Journal Article↗
PubMed2000

Biotransformation of the anti-angiogenic compound SU5416.

SU5416 [3-(3,5-dimethyl-1H-pyrrol-2-ylmethylene)-1, 3-dihydro-indol-2-one], an inhibitor of VEGF (vascular endothelial growth factor) receptor tyrosine kinase, Flk-1/KDR (fetal liver kinase 1/kinase insert domain-containing receptor), also known as VEGF receptor 2 (VEGFR2) is in advanced clinical trials for treatment of AIDS-related Kaposi's sarcoma and colorectal and nonsmall cell lung cancers. Since this chemical class has not been studied previously with therapeutic intent, the present study was designed to investigate the in vitro metabolism of SU5416 by mouse, rat, dog, monkey, and human liver microsomes and to identify the major metabolites of SU5416. An HPLC procedure was developed and validated to resolve and quantify SU5416 and its metabolites. To evaluate the in vitro metabolism of SU5416, pooled liver microsomes from mice, rats, dogs, monkeys, and humans were incubated with SU5416 (25 microM) in the presence of an NADPH-generating system. In the presence of NADPH, mouse, rat, dog, monkey, and human liver microsomes converted SU5416 to at least 12, 9, 9, 7, and 6 polar metabolites, respectively. Microsomal metabolism of SU5416 showed marked species differences in the levels of different metabolites formed. The overall rate of SU5416 metabolism by liver microsomes from the species examined followed the rank order: monkey > or = mouse approximately rat > dog > human. Two major metabolites of SU5416 were identified, a hydroxymethyl derivative of SU5416 (M12) and a carboxylic acid derivative of SU5416 (M6), by spectroscopic methods and comparison with authentic compounds. Both of these oxidative metabolites were further metabolized in vivo through glucuronidation. The metabolic fate of SU5416 in microsomes from various species as well as data from in vivo biotransformation in the rat are discussed.

Angiogenesis Inhibitors↗