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Biomedical subjects

W Schmidt

Publications and source records attributed to W Schmidt.

At least 109 records · Page 6Linked to original sources

Enoximone maintains intestinal villus blood flow during endotoxemia.

BACKGROUND: The objective of this study was to determine the effects of a continuous infusion of the phosphodiesterase inhibitor enoximone on mucosal villus blood flow in a normotensive model of endotoxemia. METHODS: Twenty-four anesthetized and ventilated rats underwent laparotomy and a ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without phosphodiesterase inhibitor pretreatment (LPS group); or infusion of LPS with enoximone pretreatment (10 microg x kg(-1) x min(-1), start 30 min before LPS infusion, enoximone group), or infusion of an eqivalent volume of NaCl 0.9% (control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = DA, and mean erythrocyte velocity within the arterioles = VE) were measured 30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal villus blood flow was calculated from DA and VE. RESULTS: In this normotensive endotoxemia model MAP remained stable in the control and the LPS group but significantly decreased in the enoximone group. The endotoxin-induced decrease of VE and DE of central arterioles of mucosal villi could be prevented. Thus, mucosal villus blood flow did not decrease compared to the LPS group. CONCLUSIONS: Our results indicate that enoximone during an early stage of sepsis contributes to systemic hypotension but prevents mucosal hypoperfusion.

Analysis of Variance↗

Discovery of a comet by its Lyman-alpha emission

Several searches for near-Earth objects have recently been initiated, as a result of increased awareness of the hazard of impacts on the Earth. These programs mainly search for asteroids, so amateur astronomers can still contribute to the discovery of comets, especially out of the orbital plane of the Solar System. An ideal way to search for comets would be to use a spaceborne instrument capable of imaging the whole sky on a daily basis in a systematic and repeatable way. Such an instrument already exists on the solar observatory SOHO; it operates at the Lyman-alpha wavelength of neutral hydrogen, which is the main component of the emission cloud of a comet. Here we report the discovery, using archival data from this satellite, of a hitherto unnoticed comet which reached a perihelion of 1.546 a.u. on 26 June 1997. We derive the water production rate of the comet as a function of time and find that it increases after perihelion, like that of comet Halley.

Journal Article↗

Regulatory science: a special update from the United States Food and Drug Administration: Preclinical issues and status of investigation of botanical drug products in the United States.

A recent survey was conducted across the therapeutic divisions within the CDER, U.S. FDA regarding the number of submissions related to botanical drug products over the past ten years. The overall number of botanical submissions as expressed in the parenthesis are as follows: 1990 (1), 1991 (4), 1992 (4), 1993 (5), 1994 (6), 1995 (5), 1996 (13), 1997 (16), 1998 (10). In the total of 64 counted, 50 of them are submitted in original IND and the rest (14) in pre-IND format. The therapeutic categories are focused on dermatological and topical (19), anti AIDS/antiviral (12), oncologic (13), neuropharmacologic (8), endocrine and metabolic (3), urologic (2), tobacco (2), and cardio-renal products (1). The regulatory actions taken on these submissions showed that 68% of them are evaluated as safe to proceed for the human trials, while the rest (32%) of submissions required agency's regulatory guidance. Among the submissions that required further guidance, 81% were deficient in preclinical pharmacology/toxicology information and the rest (19%) lacks information in other areas (chemistry, clinical protocols). Following agency's guidance, 93% of the submissions that were put on hold were allowed to proceed. In summary, a total of 94% of all the botanical INDs submitted to the agency were allowed to proceed without additional animal toxicity studies conducted. In conclusion, this survey indicates that the growing public interest in botanical supplements has prompted more formal evaluation of the efficacy/safety claims of these products.

Databases, Factual↗

Design and dosimetry of a novel 90Y beta source to prevent restenosis after angioplasty.

PURPOSE: Post-dilatation irradiation of the vessel wall is currently under investigation for prevention of restenosis after balloon dilatation. For the irradiation, special sources were designed for animal experiments which would give equivalent irradiation conditions and doses to the vessel wall that would later be employed for human application. METHODS AND MATERIALS: For the planned irradiations, a specially designed yttrium-wire of 0.45-mm diameter coated with a thin shrink tube to prevent contamination was deployed. Several leakage tests applied before and after application proved that the irradiation source was leakproof. Dosimetry was performed by using 0.1-mm-thick thermoluminescent dosimeters (TLD-100) calibrated against a primary standard. A shielding transport and application container was designed to facilitate the handling of the source during use, while reducing exposure of the medical personnel. RESULTS: The designed source proves to be flexible for the insertion into proximal coronary vessels, and positioning at the site of stenosis. It provides an optimum protection of the animal and requires little radiation protection efforts on behalf of the medical staff. Dosimetric calculations and measurements showed that a centering of the source inside the vessel could be achieved with a maximum deviation of 50% between maximum and average dose levels. CONCLUSION: A yttrium-90 beta brachytherapy source was designed which provides high flexibility within proximal coronary arteries, ensures an adequate centering inside the artery, and provides irradiation conditions to the vessel wall of the experimental animal comparable to the application inside a human artery.

Angioplasty, Balloon, Coronary↗

Statoliths in Phycomyces: characterization of octahedral protein crystals.

To identify the molecular mechanisms of gravitropism in the fungus Phycomyces blakesleeanus we determined several biochemical and physical parameters of paracrystalline protein bodies, so-called octahedral crystals. The crystals, which are present throughout the central vacuoles of the sporangiophore, function as statoliths (Schimek et al., 1999a,b). They possess an average volume of 9.96 microm(3) and a specific mass of 1.26 g cm(-3). SDS-PAGE of purified crystals shows three major proteins with relative molecular masses of 16, 46.5, and 55 kDa. These proteins are absent in gravitropism mutants which lack the crystals. Phototropism mutants (genotype mad) which are graviresponsive (class 1) and those which are defective in gravitropism (class 2) contain the crystals and the three associated proteins. Absorption spectra of isolated crystals and in situ absorption spectra of growing zones indicate the presence of chromophores, probably oxidized and reduced flavins. The flavin nature of the chromophores is also indicated by their fluorescence properties. It appears likely that the chromophores represent an essential part of the statoliths and thus the gravitropic transduction chain.

Crystallization↗

Effect of endotoxemia on hepatic portal and sinusoidal blood flow in rats.

A decrease in liver blood flow leads to dysfunction of hepatocytes and Kupffer cells, with subsequent local and systemic liberation of proinflammatory mediators that may maintain systemic inflammatory response syndrome (SIRS) and may lead to multiple organ dysfunction syndrome (MODS). There is only limited knowledge on the hepatic micro- and macrocirculation during sepsis or endotoxemia. Therefore, the aim of our study was to investigate alterations in hepatic portal blood flow (PBF) and sinusoidal blood flow (SBF) during endotoxemia. In male Wistar rats endotoxemia was induced by continuous infusion of 2 mg/kg/h lipopolysaccharides from Escherichia coli 026:B6 immediately after baseline measurements (n = 8). The control group (n = 8) received an equivalent volume of Ringer's solution. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), PBF, and SBF were measured at baseline and 60 and 120 min after induction of endotoxemia. PBF was measured using an ultrasonic flow probe that was positioned around the portal vein. SBF was detected by in vivo videomicroscopy of the left liver lobe. In the LPS group MAP decreased, but CO remained at baseline values. During endotoxemia PBF decreased significantly from 23 +/- 3 to 15 +/- 4 mL/min (60 min) and 16 +/- 3 mL/min (120 min). SBF also significantly decreased to 68.5% (60 min) and 57.1% (120 min) of baseline value. Our results demonstrate that during early endotoxemia hepatic macro- and microcirculatory perfusion is significantly decreased despite unchanged CO. This early reduction of hepatic perfusion might be caused by an increased hepatic vessel resistance as a consequence of liberation of vasoconstrictive mediators or/and by a decrease in intestinal perfusion.

Animals↗

Influence of amrinone on tissue oxygenation of jejunal mucosa during endotoxemia.

BACKGROUND: The intestinal mucosa is the portion of the gut most susceptible to impaired perfusion and oxygen delivery. The phosphodiesterase (PDE) inhibitor amrinone has been proposed to improve oxygen delivery and tissue perfusion during sepsis. The objective of this study was to investigate the effects of amrinone on arterial oxygenation (Pao(2)) and tissue oxygenation (Ptio(2)) of jejunal mucosa during endotoxemia. MATERIALS AND METHODS: Forty anesthetized and ventilated rats were laparotomized and a jejunal portion was exteriorized and fixed on a plexiglass stage. The jejunum was punctured and a Clark-type microcatheter Po(2) probe and a microthermocouple were placed on the mucosa to measure Ptio(2). The animals were randomly assigned to receive one of the four treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without amrinone pretreatment (LPS group); infusion of LPS with amrinone pretreatment (40 microg/kg/min, start 30 min before LPS infusion, amrinone + LPS group); no treatment with either amrinone or LPS (control group); treatment with amrinone without LPS infusion (amrinone group). Mean arterial pressure (MAP), heart rate (HR), Pao(2), and Ptio(2) were measured 30 min before and 0, 60, and 120 min after induction of endotoxemia. RESULTS: MAP remained stable in the control and LPS groups. In the amrinone + LPS group MAP decreased within the first 30 min of amrinone infusion and decreased further during endotoxemia. Pao(2) remained stable in the control group and decreased in the LPS group. This endotoxin-induced decrease in Pao(2) was attenuated in the amrinone + LPS group. The mucosal Ptio(2) decreased in the LPS group but remained stable in both the control and amrinone + LPS groups. CONCLUSIONS: Pretreatment with amrinone was able to diminish a decrease in Pao(2) during endotoxemia, indicating that pulmonary dysfunction was attenuated. Endotoxin-induced tissue hypoxia of the intestinal mucosa, however, could be fully prevented, indicating that an additional improvement in compromised tissue perfusion had occurred.

Amrinone↗

Role of platelet-activating factor in leukocyte-independent plasma extravasation and mast cell activation during endotoxemia.

BACKGROUND: Independently from leukocyte adherence, endothelial factors and mast cell activation seems to promote microvascular permeability. Platelet-activating factor (PAF) has been shown to play a significant role in endotoxin-induced leukocyte adherence. The aim of our study was to investigate if there is also a role for PAF in mediating leukocyte-independent microvascular permeability changes and activation of mast cells during endotoxemia. Therefore, during endotoxemia microvascular permeability and mast cell activation were determined after inhibition of L-selectin-mediated leukocyte adherence by fucoidin and after inhibition of PAF effects by the PAF receptor antagonist BN52021. MATERIALS AND METHODS: In male Wistar rats, red cell velocity (V(RBC)), venular wall shear rate, microvascular permeability, leukocyte adherence, and mast cell activation were determined in mesenteric postcapillary venules using intravital microscopy at baseline and 60 and 120 min after start of a continuous infusion of endotoxin (ETX; 2 mg/kg/h, Escherichia coli O26:B6) (ETX group). Animals in the FUCO/ETX group received fucoidin (25 mg/kg body wt) in addition to the procedure described above. Animals in the FUCO/ETX/PAF-ANT group received fucoidin and the PAF receptor antagonist BN52021 (5 mg/kg body wt) prior to the continuous endotoxin infusion. Control animals (control group) received only equivalent volumes of NaCl 0.9%. RESULTS: There were no microhemodynamic and macrohemodynamic differences between groups. In all endotoxin-challenged groups macromolecular leakage and mast cell activity increased significantly, starting at 60 min. Both macromolecular leakage and mast cell activity were significantly higher in the FUCO/ETX group than in the FUCO/ETX/PAF-ANT group and control group. Differences in macromolecular leakage between groups were significant at 120 min. Differences in mast cell activity between groups were significant at 60 and 120 min. CONCLUSIONS: The results of our study demonstrate a leukocyte-independent plasma extravasation that can be inhibited by the PAF receptor antagonist BN52021, indicating the involvement of PAF in the pathophysiology of leukocyte-independent microvascular damage during early endotoxemia. Mast cell activity seems to precede leukocyte-independent macromolecular leakage.

Animals↗

Is absolute noninvasive temperature measurement by the Pr[MOE-DO3A] complex feasible.

Recently, the feasibility of the praseodymium complex of 10-(2-methoxyethyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7-tr iacetate (Pr[MOE-DO3A]) for non-invasive temperature measurement via 1H spectroscopy has been demonstrated. Particularly the suitability of the complex for non-invasive temperature measurements including in vivo spectroscopy without spatial resolution as well as first spectroscopic imaging measurements at low temporal resolution (> or = 4 min) and high temporal resolution (breath hold, approximately 20 s) has been shown. As of today, calibration curves according to the particular experimental conditions are necessary. This work aims to clarify whether the Pr[MOE-DO3A] probe in conjunction with 1H-NMR spectroscopy allows non-invasive absolute temperature measurements with high accuracy. The measurement results from two different representative media, distilled water and human plasma, show a slight but significant dependence of the calibration curves on the surrounding medium. Calibration curves in water and plasma were derived for the temperature dependence of the chemical shift difference (F) between Pr[MOE-DO3A]'s OCH3 and water with F = -(27.53 +/- 0.04) + (0.125 +/- 0.001) x T and F = -(27.61 +/- 0.02) + (0.129 +/- 0.001) x T, respectively, with F in ppm and T in degrees C. However, the differences are minuscule even for the highest spectral resolution of 0.001 ppm/pt, so that they are indistinguishable under practical conditions. The estimated temperature errors are +/- 0.18 degrees C for water and +/- 0.14 degrees C for plasma and with that only slightly worse than the measurement accuracy of the fiber-optical temperature probe (+/- 0.1 degrees C). It can be concluded that the results obtained indicate the feasibility of the 1H spectroscopy method in conjunction with the Pr[MOE-DO3A] probe for absolute temperature measurements, with a maximum accuracy of +/- 0.2 degrees C.

Agar↗

Milrinone improves intestinal villus blood flow during endotoxemia.

PURPOSE: To determine whether the compromised intestinal villus blood flow in a rat model of endotoxemia could be improved by continuous infusion of the phosphodiesterase (PDE) inhibitor milrinone. METHODS: Twenty-four anesthetized and ventilated rats were laparotomized and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides without phosphodiesterase inhibitor pretreatment (=LPS group); or infusion of LPS with milrinone pretreatment (= milrinone group), or without infusion of LPS or milrinone (=control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) and mean erythrocyte velocity within the arterioles= V(E)) were measured 30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal villus blood flow was calculated from D(A) and V(E). RESULTS: In the milrinone group MAP decreased 60 min after induction of endotoxemia whereas it remained stable in the control and the LPS group. In both groups given endotoxin V(E) decreased after start of LPS infusion. In contrast, D(A) decreased in the LPS group, but increased in the milrinone group after 120 min of endotoxemia. Thus, the endotoxin-induced decrease of intestinal villus blood flow was diminished but not fully restored by milrinone infusion. CONCLUSION: Our results indicate that milrinone has some beneficial microcirculatory effects during endotoxemia. Although it contributed to systemic hypotension, it attenuated intestinal mucosal hypoperfusion.

Animals↗

Uterine rupture in pregnancy subsequent to previous laparoscopic electromyolysis. Case report and review of the literature.

Reports about uterine rupture in pregnancy subsequent to previous laparoscopic surgery are not frequent. This may be due to the lack of long term follow up of patients who had undergone this surgery rather than the rarity of this complication. A case of uterine rupture subsequent to laparoscopic myomectomy is reported. An increasing rate of the occurrence of this complication is reviewed in current literature, thus reiterating the need for more stringent selection criteria for patients who benefit from this surgical technique.

Adult↗

Gravity-induced absorbance changes in Phycomyces: a novel method for detecting primary responses of gravitropism.

The negative gravitropism of the sporangiophores of Phycomyeces blakesleeanus Burgeff is elicited by different sensory inputs, which include flexure of the growing zone, buoyance of lipid globules and sedimentation of paracrystalline proteins, so-called octahedral crystals (C. Schimek et al., 1999a, Planta 210: 132-142). Gravity-induced absorbance changes (GIACs), which are associated with primary events of gravity sensing, were detected in the growing zones of sporangiophores. After placing sporangiophores horizontally, GIACs were detected after a latency of about 5 min, i.e. 15-25 min prior to gravitropic bending. The spectroscopic properties of the GIACs indicate that gravitropic stimulation could imply the reduction of cytochromes. The GIACs were spectrally distinct from light-induced absorbance changes (LIACs), showing that the primary responses of the light and gravity transduction chains are different. A dual stimulation with gravity and light generated GIAC-LIACs which were distinct from the absorbance changes occurring after the single stimuli and which indicate that light and gravity interact early in the respective transduction chains.

Cytochromes↗

Xanthone 6-hydroxylase from cell cultures of Centaurium erythraea RAFN and Hypericum androsaemium L.

Xanthone 6-hydroxylase activity was detected in the microsomal fractions from two plant cell cultures. The enzyme from cultured cells of Centaurium erythraea (Gentianaceae) exhibited absolute specificity for 1,3,5-trihydroxyxanthone as substrate, whereas xanthone 6-hydroxylase from cell cultures of Hypericum androsaemum (Hypericacaea) preferred the isomeric 1,3,7-trihydroxyxanthone but used 1,3,5-trihydroxyxanthone also to a small extent. Both xanthones were regioselectively hydroxylated in position 6. The xanthone 6-hydoxylases are cytochrome P450 monooxygenases, as shown by their dependence on NADPH and molecular oxygen and their inhibition by carbon monoxide and typical P450 inhibitors. In both cell cultures, xanthone accumulation was preceded by an increase in xanthone 6-hydroxylase activity.

Cells, Cultured↗

Influence of amrinone on intestinal villus blood flow during endotoxemia.

PURPOSE: The objective of this study was to determine the effects of a continuous infusion of the phosphodiesterase (PDE) inhibitor amrinone on mucosal villus blood flow in a normotensive model of endotoxemia. MATERIALS AND METHODS: Twenty-four anesthetized and ventilated rats underwent laparotomy, and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without phosphodiesterase inhibitor pretreatment (LPS group); or infusion of LPS with amrinone pretreatment (40 microg/kg/min, start 30 minutes before LPS infusion) (amrinone group), or infusion of equivalent volumes of NaCl 0.9% (control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) and mean erythrocyte velocity within the arterioles = VE) were measured 30 minutes before and at 0, 60, and 120 minutes after induction of endotoxemia. Mucosal villus blood flow was calculated from D(A) and VE. RESULTS: In this normotensive endotoxemia model, MAP remained stable in the control and the LPS group but significantly decreased in the amrinone group.The endotoxin-induced decrease of V(E) and D(A) of central arterioles of mucosal villi could be attenuated and prevented, respectively. Thus, the endotoxin-induced decrease of mucosal villus blood flow was diminished but not fully restored by amrinone infusion. CONCLUSION: Our results indicate that amrinone during an early stage of sepsis is of limited value. It attenuates mucosal hypoperfusion but contributes to systemic hypotension.

Amrinone↗

[Results of different incisions in treatment of carpal tunnel syndrome].

Various surgical techniques are used to treat the carpal tunnel syndrome. Besides the endoscopic technique, the "open-standard-technique" and the "Millesi technique" are very common. The success and the complication rate of all these techniques are discussed controversially. However, the aim of the current prospective study was to investigate the various open techniques to find the most successful method with the least complications. Therefore, 64 patients (20 male, 44 female) were examined after surgery. 23 patients were operated with an "Open-Standard-Technique" (OST) including long incision, 22 patients were treated according to the "Millesi-Technique", and 19 patients with the "Short-Incision-Technique" (SIT). All patients were evaluated using a prospectively designed examination check-list. Comparing these various techniques, the OST and the SIT yielded the best results with regard to complications, the SIT seems to be the most successful technique.

Adult↗

Xanthones in cell cultures of Hypericum androsaemum.

Cell cultures of Hypericum androsaemum contain an array of prenylated xanthone aglycones and their glucosides, when grown in modified B5 medium in the dark. Derivatives of 1,3,6,7-tetrahydroxyxanthone prevail over compounds with the 1,3,5,6-oxygenation pattern. 1,7-Dihydroxyxanthone was also isolated. Xanthone accumulation parallels cell growth, is repressed by light and strongly influenced by the culture medium used.

Cells, Cultured↗