Biomedical subjects

M Hofer

Publications and source records attributed to M Hofer.

At least 73 records · Page 4Linked to original sources

PubMed1999

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine act additively to enhance the hemopoietic spleen colony formation in irradiated mice.

The effects of combined administration of two drugs elevating extracellular adenosine, namely dipyridamole (DP) and adenosine monophosphate (AMP), and granulocyte colony-stimulating factor (G-CSF) on hemopoietic stem cells in vivo were investigated. The experiments were performed on mice using the endogenous spleen colony formation in gamma-irradiated animals as an endpoint. The results have shown that DP and AMP act additively with G-CSF to enhance spleen colony formation and thus the erythroid repopulation of the spleen. These findings indicate that the signaling pathways of G-CSF and drugs elevating extracellular adenosine can interact at the level of primitive hemopoietic stem cells. The enhancement of hemopoiesis-stimulating effects of G-CSF by DP and AMP, which are low-priced and clinically available drugs, could improve the cost-effectiveness of the therapy with G-CSF.

Adenosine↗

PubMed1998

Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only. Swiss HIV Cohort Study.

Persons with immune deficiency may present with atypical results in serological tests for hepatitis B virus (HBV). Frozen serum specimens that were sequentially obtained over time from a cohort of 57 HIV-infected patients, all of whom tested positive only for antibody to hepatitis B core antigen (anti-HBcAg), were therefore retested for HBV markers, including HBV DNA. The results were assessed for their time course and correlated with clinical data and alanine aminotransferase (ALT) values. Forty-eight patients were male; intravenous drug users constituted the principal risk group (n = 30), followed by homosexual men (n = 22). Thirty-three persons tested positive for antibody to hepatitis C virus (anti-HCV). During a median of 31 months from the first to the last serum, anti-HBcAg remained the sole marker of HBV infection in 98.2% of the patients. Polymerase chain reaction (PCR) to detect DNA for HBV core and HBV surface gene was positive in 126 (62.4%) and 121 (59.9%) of all 202 serum samples, respectively. Over time, HBV DNA was detected at least once in 51 (89.5%) patients. In contrast, decomplexed hepatitis B surface antigen (HBsAg) was detected at least once in 14 (24.6%) patients. Among patients positive for HBV DNA and negative for anti-HCV, eight (36.4%) of 22 had chronic hepatitis (ALT elevation > or = 6 months) that was attributable only to persisting HBV infection. Similarly, 12 (41.4%) of 29 patients positive for both HBV DNA and anti-HCV had chronic viral hepatitis, but their ALT values were significantly higher. In HIV-infected patients, anti-HBcAg as the sole serological HBV marker detected must be considered indicative of chronic HBV infection and is in part associated with chronic hepatitis and ALT elevation.

Adult↗

PubMed1998

Validated computation of physiologic flow in a realistic coronary artery branch.

The pulsatile flow field in an anatomically realistic model of the bifurcation of the left anterior descending coronary artery (LAD) and its first diagonal branch (D1) was simulated numerically and measured by laser Doppler anemometry. The inlet velocity profiles used in the computer simulation and in the physical experiments were physiologically realistic. The computational geometric model was developed on the basis of a digitized arterial cast. The curvature of the LAD over the cardiac surface leads to axial velocity profiles which are slightly skewed towards the epicardial wall. Downstream of the bifurcation, a strong skewing occurs towards the flow divider walls as a result of branching. Locally, the wall shear stress component caused by the complex secondary velocity can be as high as the axial component. The wall shear stress representation from a cell-based perspective exhibits low shear stress and large deviation from the time-averaged shear stress direction during systole. In diastole, the instantaneous wall shear stress direction nearly corresponds to the mean direction. The comparison of computed and measured axial velocity results shows generally good agreement. In contrast to computed flow patterns in simpler geometries constructed from cylindrical tubes, the flow field is found to be smoother, presumably reflecting the adaptation of the vascular contour to the contained flow.

Algorithms↗

PubMed1998

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice.

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multilineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive states induced by radiation exposure.

Adenosine↗

PubMed1998

Transjugular intrahepatic portosystemic shunts: improved evaluation with echo-enhanced color Doppler sonography, power Doppler sonography, and spectral duplex sonography.

OBJECTIVE: We assessed the feasibility of contrast-enhanced color Doppler, power Doppler, and spectral duplex sonography for visualization and quantification of flow through transjugular intrahepatic portosystemic shunts (TIPS) in patients in whom the baseline sonographic evaluation was unsatisfactory. SUBJECTS AND METHODS: Thirty-three patients underwent color Doppler, power Doppler, and spectral duplex sonography after TIPS insertion or before TIPS revision (mean time interval +/- SD, 1 +/- 1 day). All sonograms were obtained before and after patients received echo-enhancing contrast material. Sonography was evaluated with regard to presence or absence of flow in the mid portion, portal segment, and hepatic segment of the shunt. The maximal peak velocity was measured in the mid portion of the shunt. For identifying and quantifying stenoses, the percentage of luminal diameter reduction was calculated at the tightest part of the shunt. Shunt angiography and measurements of portosystemic pressure gradients were independently evaluated and compared with the sonographic findings. RESULTS: Flow visualization on unenhanced color Doppler sonography was significantly improved through the use of power Doppler sonography and contrast-enhanced color Doppler and power Doppler sonography (p < .01). Between contrast-enhanced power Doppler and contrast-enhanced color Doppler sonography, a significant difference was found in the portal and hepatic segments (p < .05). All shunt stenoses (n = 8) and occlusions (n = 3) were revealed by power Doppler sonography, whereas color Doppler sonography failed to reveal six of eight stenoses. Compared with unenhanced sonography, the quality of spectral duplex sonography was improved in eight patients after contrast enhancement (p < .05). Maximal peak velocity ranged from 54 to 252 cm/sec (mean +/- SD, 132.7 +/- 52.1 cm/sec) in normal shunts and from 24.5 to 70.0 cm/sec (mean +/- SD, 45.0 +/- 18.9 cm/sec) in stenosed shunts. No correlation was found between maximal peak velocity and portosystemic pressure gradients (r = .28). CONCLUSION: Unenhanced power Doppler and contrast-enhanced color and power Doppler sonography can be helpful in the assessment of TIPS status in patients who previously underwent unsatisfactory sonography. These techniques may allow anatomic evaluation and quantification of shunt stenosis in most patients. Contrast enhancement may also considerably improve the quality of spectral duplex sonography.

Adult↗

PubMed1998

Radioprotective effects of flurbiprofen and its nitroderivative.

Radioprotective effects of two non-steroidal anti-inflammatory drugs, flurbiprofen (FBP) and its novel nitroderivative flurbiprofen 4-nitroxybutylester (NO-FBP), which exhibits decreased gastrointestinal toxicity, were compared in mice. The drugs were administered in equimolar single doses, 2 hours before whole-body gamma-irradiation of the animals. After a sublethal radiation dose of 6.5 Gy, significantly increased numbers of endogenous haemopoietic spleen colonies and enhanced granulopoiesis were found in mice given either FBP or NO-FBP, when compared to vehicle-treated controls. There were no differences in the effectiveness of either drug to enhance postirradiation haemopoietic recovery. Survival of FBP- or NO-FBP-treated mice subjected to a lethal dose of 9.5 Gy was slightly but insignificantly enhanced, both drugs showing the same effect. These results clearly indicate the ability of both drugs to enhance haemopoietic recovery after sublethal radiation exposure and the absence of unfavourable effects under higher radiation doses. Because of its lower potential for gastrointestinal damage, NO-FBP seems to be a promising drug, which can find a use in the protection of postirradiation myelosuppression.

Animals↗

PubMed1997

1H T1 and T2 measurements of the MR imaging contrast agents Gd-DTPA and Gd-DTPA BMA at 1.5T.

We report in vitro T1 and T2 relaxation studies for the open-chain complexes Gd-DTPA and Gd-DTPA BMA. Measurements were performed on phantoms containing aqueous and plasma solutions of different concentrations by MR imaging in a 1.5T superconducting whole-body scanner. Longitudinal relaxation times T1 were evaluated from serial turbo-FLASH experiments for concentrations less than 1 mM, whereas for larger concentrations the values were obtained from a standard inversion recovery (IR) sequence. Transverse relaxation times T2 were determined using multi-echo spin-echo MRI protocols. The T1 and T2 relaxivities of the nonionic Gd-DTPA BMA are similar to those of the Gd-DTPA. The temperature dependencies of the relaxivities were determined over a temperature interval ranging from 21 to 50 degrees C and were found to be slightly different for the two contrast agents. In the case of Gd-DTPA BMA a larger deviation of the expected temperature behavior of the relaxivities was observed as compared with Gd-DTPA. Deviations from a strictly linear dependence of relaxation times on temperature were found at lower concentrations in aqueous solutions. In plasma solutions a high T1/T2 ratio was observed for low concentrations, which decreased monotonically with increasing concentrations.

Contrast Media↗

PubMed1997

Reliability and practicability of bacteriological monitoring of beef carcass contamination and their rating within a hygiene quality control programme of abattoirs.

A total of 9600 swab samples from 900 carcasses originating from ten different abattoirs were subjected to bacteriological examination. Two sampling sites, brisket and forearm, consistently showed the highest contamination rates. The following sites are recommended for sampling: on the lateral side of the carcass neck, forearm, shoulder, brisket and abdomen. The neck is recommended for the medial side. Compared to the large variance of contamination either on individual carcasses or between different carcasses, the differences in the variance of results between double swab and incision sampling techniques should be of minor importance. Considering this big variance of colony counts, it is suggested to take five to six swab samples from each of at least ten to 15 carcasses once a month. With a view to a more differentiated and evident evaluation the results should be recorded in a 'box plots' and not in the form of mean values and standard deviations. The data confirms bacteriological monitoring of beef carcasses as a useful tool for the verification of slaughter hygiene.

Animals↗

PubMed1997

Stimulation of hemopoietic colony formation from mouse marrow cells in vitro using human dialyzable leukocyte extracts-IMMODIN-SEVAC.

The influence of dialyzable extract from human leukocytes (DLE) on the in vitro growth of the granulocyte-macrophage colony-forming cell (GM-CFC) colonies from progenitors of mouse bone marrow cells was studied. DLE alone did not induce the colony growth but it modulated the number of colonies if administered together with a colony-stimulating factor (CSF). The costimulatory effect prevailed in a broad range of DLE dilution and the index of increase was enhanced with the lowering of the CSF concentration. The costimulatory augmentation of clonal proliferation of GM-CFC with DLE was further strengthened by addition of indomethacin, thus indicating an intervening role of prostaglandins in the modulatory influence of DLE.

Animals↗

PubMed1997

Enhancement of haemopoietic spleen colony formation by drugs elevating extracellular adenosine: effects of repeated in vivo treatment.

The potential role of adenosine receptor signalling in the amplification of haemopoietic stem cells in vivo was investigated. Elevation of extracellular adenosine in mice was induced by the joint administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, an adenosine prodrug. The response of haemopoietic stem cells to the drug treatment was measured by endogenous spleen colony-forming assay in sublethally gamma-irradiated animals. The combination of drugs was administered before irradiation either singly or repeatedly at 24 h intervals. The results demonstrated the possibility of enhancing the spleen colony formation by the drug treatment. The highest stimulatory effect on spleen colony counts and on the colony sizes occurred after 3-4 injections of the drugs. Higher spleen colony responses were observed under injection regimens terminated 3 h before irradiation, as compared to those terminated 24 h before the radiation exposure. The results are interpreted as an evidence of the expansion of the stem cell pool. A tolerance to this stimulatory action developed after more than 3 injections of the drugs.

Adenosine↗

PubMed1996

Numerical study of wall mechanics and fluid dynamics in end-to-side anastomoses and correlation to intimal hyperplasia.

In order to analyse the wall mechanics and the flow dynamics in compliant vascular distal end-to-side anastomoses, computer simulation has been performed. In a model study the effect of compliance mismatch on the wall displacements and on the intramural stresses as well as the influence of wall distensibility on the flow patterns are demonstrated applying two distensible models with different graft elasticity. In addition, the flow in a rigid model simulating a vein graft without adaption of the venous lumen has been investigated. The geometries for these models were obtained from a concurrent experimental study, where the formation of distal anastomotic intimal hyperplasia (DAIH) was studied in untreated and externally stiffened autologous venous grafts in sheep. In the flow study the time-dependent, three-dimensional Navier-Stokes equations describing the motion of an incompressible Newtonian fluid are applied. The vessel wall is modelled using a geometrically non-linear shell structure. In an iteratively coupled approach the transient shell equations and the governing fluid equations are solved numerically using the finite element method. In both compliant models maximum displacement and areas of steep stress gradients are observed in the junction region along the graft-artery intersection. The comparison of the normal deformations and the distribution and magnitude of intramural stress shows quantitative differences. The graft elasticity acts as a regulating factor for the deformability and the stress concentration in the junction area: In the model with high graft-elasticity maximum normal deformation at the side wall is 17%. This is twice as large as in the stiff graft model and maximum principle stress at the inner surface differs by one order of magnitude. The numerical results concerning the flow patterns indicate strongly skewed axial velocity profiles downstream of the junction, large secondary motion, flow separation and recirculation on the artery floor opposite the junction and at the inner wall downstream of the toe. In these regions a correlation between the time-averaged fluid wall shear stress and intimal thickening found in the animal experiment can be observed, whereas the pronounced formation of DAIH at the suture line seems to be mainly dependent on wall mechanical factors such as intramural stress and strain.

Adaptation, Physiological↗

PubMed1996

Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells.

In the neurological mutant mouse weaver, granule cell precursors proliferate normally in the external germinal layer of the cerebellar cortex, but fail to differentiate. Granule neurons purified from weaver cerebella have greatly reduced G protein-activated inwardly rectifying K+ currents; instead, they display a constitutive Na+ conductance. Expression of the weaver GIRK2 channel in oocytes confirms that the mutation leads to constitutive activation, loss of monovalent cation selectivity, and increased sensitivity to three channel blockers. Pharmacological blockade of the Na+ influx in weaver granule cells restores their ability to differentiate normally. Thus, Na+ flux through the weaver GIRK2 channel underlies the failure of granule cell development in situ.

Animals↗

PubMed1996

[MRI tomographic blood volume measurements in the diagnosis of a stroke: the results of a clinical pilot study].

PURPOSE: In this study the sensitivity of proving a stroke using regional cerebral blood volume (rCBV) maps were investigated. Another aim was to evaluate the strength of the ischaemia. METHODS: Seven patients were examined during the acute phase of a stroke, eight during the subacute or chronically stage. To calculate rCBV-maps of one slice low dosed Gd-DTPA was injected as a bolus. Using the relaxation-effect the obtained signal intensity-time curves were converted pixel-wise to rCBV images. For the region of the infarction rCBV ratios were calculated relative to the corresponding area in the contralateral hemisphere. RESULTS: Only 63% of the investigations carried out during the acute phase were utilizable. In all those cases a decrease of rCBV was found. The infarct area could only visually recognized if the rCBV ratio was lower than 0.7. The ratios of completely and partial necrotic areas of the infarctions were 0.481 and 1.028 respectively. With a p = 0.0015 these values are even statistically different. CONCLUSIONS: During the acute stage the sensitivity of the rCBV measurement was not as high as that of morphological MR imaging. However, rCBV maps make it possible to estimate the strength of the ischaemia even during the first hours.

Adult↗

PubMed1996

Measurement of cerebral blood volume via the relaxing effect of low-dose gadopentetate dimeglumine during bolus transit.

PURPOSE: To quantify regional cerebral blood volume (rCBV) on the basis of the enhancement of blood proton relaxation rates after intravenous administration of gadopentetate dimeglumine. METHODS: A series of sequential MR images on one section was recorded during bolus transit with a standard fast low-angle shot sequence. The signal-intensity curves were converted into corresponding concentration-time curves from which rCBV images were calculated. RESULTS: The functional parameter images of rCBV were calculated pixel-by-pixel for two patients who had received a 1-second bolus injection of 1 mmol of gadopentetate dimeglumine. In a larger series of 62 patients, a mean blood volume of 4.6 +/- 1.6 vol% was determined for normal brain tissue. CONCLUSIONS: The relaxing effect of a contrast agent can be used to determine blood volume quantitatively. The results are in agreement with those obtained by nuclear medicine techniques. The proposed method requires no special hardware, and can thus be implemented on clinical MR scanners.

Aged↗

PubMed1996

Intracranial stenoocclusive disease: MR angiography with magnetization transfer and variable flip angle.

PURPOSE: To assess time-of-flight MR angiography that uses magnetization transfer contrast (MTC) pulses, tilted optimized nonsaturating excitation (TONE), and a 256 x 512 image matrix for the detection of small intracranial arteries and for the detection and quantification of intracranial arterial stenoocclusive disease. METHODS: To assess anatomic sensitivity, six interpreters, in a blinded fashion, reviewed the MTC/TONE MR angiograms and selective intraarterial angiograms obtained in 70 patients within a mean interval of 5.5 days (SD, 1.5). In addition, all intracranial angiograms were evaluated with regard to presence and degree of arterial stenosis and anatomic variants. RESULTS: Interobserver correlations for determining vessel length were comparably high for both methods. A strong correlation was found between measurements obtained on MR angiograms and those obtained on intraarterial angiograms. The mean vascular length averaged across all arteries was 34.8 mm (SD, 28.1) on MR angiograms and 53.2 mm (SD, 36.8) on intraarterial angiograms. Forty-one stenoses and occlusions and 30 anatomic variants were identified with intraarterial angiography. All arterial variants and 100% of occluded vessels were graded correctly. Moreover, 80% of stenoses greater than 70% and 88% of stenoses less than 70% were quantified correctly at MR angiography. Specificity for identifying stenotic disease was 99%. CONCLUSION: Despite inferior display of vessel length, MTC/TONE MR angiography with increased spatial resolution was able to show the vast majority of high grade lesions visible at selective intraarterial angiography and may suffice for clinical decision making in many patients.

Adolescent↗

PubMed1996

Radioprotective properties of flurbiprofen.

Repeated administration of flurbiprofen, an inhibitor of prostaglandin synthesis (IPS), was found to enhance haemopoiesis in mice exposed to a sublethal dose of fractionated gamma-irradiation (5 x 3 Gy, intervals between fractions 24 h). In lethally irradiated animals (5 x 3 Gy and an additional "top-up" dose of 3.5 Gy), a significantly better survival was found in mice given flurbiprofen than in control animals receiving saline. The latter result is a new positive phenomenon not observed in earlier experiments with other IPS. The findings suggest a possibility to extend the radiation dose range, in which the administration of IPS leads to radioprotective effects, also to higher, lethal radiation doses, by administering flurbiprofen instead of previously studied IPS indomethacin or diclofenac.

Animals↗

PubMed1996

Modulation of haemopoietic radiation response of mice by diclofenac in fractionated treatment.

The effects of diclofenac, an inhibitor of prostaglandin synthesis, were studied on the acute radiation syndrome elicited in mice by fractional irradiation. Several haematological parameters were evaluated in mice irradiated with 5x2 Gy and 3x, 4x, or 5x3 Gy (intervals between fractions 24 h) from a 60Co gamma-ray source. The animals were treated with diclofenac either before each fraction or only once before the last fraction. The survival of mice was recorded after the irradiation regimen of 5x3 Gy followed by a "top-up" dose of 3.5 Gy given 24 h after the last radiation fraction. Statistically significant enhancement of the endogenous spleen colony formation and of leukopoiesis was found in mice treated with diclofenac repeatedly, as compared with both saline-treated irradiated controls and animals administered a single diclofenac dose, if a sublethal total radiation dose had been accumulated. However, following accumulation of a lethal total radiation dose, slightly impaired survival was observed in mice given diclofenac. It follows from the results that diclofenac is a suitable drug for enhancing leukopoiesis impaired by sublethal fractionated irradiation. Nevertheless, undesirable side effects of this drug negatively influence the survival of experimental animals following a lethal accumulated radiation dose.

Animals↗

PubMed1995

Synergistic effect of granulocyte colony-stimulating factor and drugs elevating extracellular adenosine on neutrophil production in mice.

Experimental evidence suggests that the activation of purinoceptors by extracellular adenosine can modulate proliferation and/or differentiation of hematopoietic cells. The present study was undertaken to investigate the potential interactions of this system of intercellular signaling with the effects of granulocyte colony-stimulating factor (G-CSF) on granulopoiesis in vivo. Elevation of extracellular adenosine in normal mice was induced by the joined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole, AMP, and G-CSF, administered either alone or in combinations, were evaluated. The agents were injected to mice in a 4-day regimen, and the hematologic endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, ie, increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC), and morphologically determined granulocytic cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of dipyridamole plus AMP administered 30 minutes before G-CSF. Furthermore, it was ascertained that the stimulatory action of dipyridamole plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 micrograms/d). At higher doses of G-CSF (6 and 9 micrograms/d), the interactions were no more evident. When combining dipyridamole, AMP, and 3 micrograms of G-CSF, peripheral neutrophils increased approximately 3.9- to 4.5-fold compared with an approximate 2.2-fold increase induced by G-CSF alone. The results indicate the possible therapeutic potential of combination therapy with G-CSF and drugs increasing extracellular adenosine.

Adenosine↗