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Biomedical subjects

R Brunner

Publications and source records attributed to R Brunner.

At least 19 recordsLinked to original sources

Improvement of macular function by membrane differential filtration in diabetic retinopathy.

BACKGROUND: Alterations of blood rheology are assumed to substantially contribute to the pathogenesis of diabetic retinopathy. Membrane differential filtration (MDF) is an extracorporeal treatment which is able to optimize rheological parameters by eliminating high molecular weight proteins and lipoproteins from the blood. The present study was designed to investigate the effects of repetitive MDF on visual function in diabetic retinopathy. METHODS: 11 patients (11 eyes) with nonproliferative or inactive proliferative diabetic retinopathy underwent three treatment cycles during a mean period of 18 weeks. The best corrected visual acuity served as the main parameter of the study. The measurement of visual acuity, visual field, biochemical and rheological parameters was carried out 24 hours pre and post each treatment cycle and at follow up. The mean follow up time was 9 weeks during the post treatment period. RESULTS: Compared to baseline examination the visual acuity improved stepwise by a mean value of 1.4 lines (p = 0.02) after the last treatment and remained stable at follow up (1.3 lines, p < 0.001). The mean defect of the visual field was reduced by 2.8 dB (p = 0.13) after the treatment period and by 2.5 dB (p = 0.016) at follow up, respectively. CONCLUSIONS: Repetitive treatment with membrane differential filtration is able to improve visual function in patients with diabetic retinopathy. The present study suggests that repetitive membrane differential filtration treatment could be a useful adjunct along with laser treatment to influence the clinical course of diabetic maculopathy.

Blood Proteins↗

The current state of extracorporeal haemorheotherapy: from haemodilution via cascadefiltration to rheohaemapheresis.

Rheological therapy aims at an improvement of organ perfusion however, it has to be stressed that the tonus of the blood vessels also plays an important role for both the blood distribution and the rheology in the micro- and the macrocirculation. Conventional rheotherapy consists of attempts to influence nutrition and life style, to apply drugs such as purin derivatives, vasodilatating or defibrinising substances and hypervolaemic (using infusion therapy), hypovolaemic, e.g., blood letting, erythrocytapheresis and--the most widely distributed- -isovolaemic haemodilution. With the introduction of centrifugal devices, and approximately 10 years later with the introduction of hollow fibre and flat sheet membrane techniques, a considerable increase of therapeutical efficacy was achieved. These technologies were successfully applied for the treatment of cellular and plasmatic hyperviscosity syndromes. The treatment of less severe diseases of the micro- and macrocirculation, vessel stenosis, vessel wall sclerosis, malformation of the blood vessel architecture, pathological clinical-chemical blood parameters and maldistribution have hardly been taken into consideration. Our group at Köln investigated different plasma differential separation techniques and demonstrated, that adsorption as well as filtration could be applied. These different techniques being 6-10 times more effective as conventional haemodilution techniques have in common high molecular weight proteins determining the viscosity of plasma and thus whole blood viscosity is removed, however differences among the different elimination techniques do exist. The rheological and clinical importance of such differences has to be determined. Applying filtration techniques for both primary and secondary separations, the concept of Rheohaemapheresis was developed. A corresponding quality program was also introduced into our clinical routine. Rheohaemapheresis is supported from the currently introduced concept of the synergetic consideration of the microcirculation. Age related macular degeneration, so far without generally accepted therapy, is a most advanced indication based on several pilot studies and a prospective, randomised controlled trial. Other diseases of the microcirculation have also successfully been treated.

Blood Component Removal↗

First experience with a ready-for-use rheohemapheresis system.

Rheohemapheresis is increasingly being used for the improvement of microcirculation in numerous diseases. The method is based on the constant-flow separation of plasma by a cell separator and the secondary filtration of plasma through a hollow-fiber membrane. A new CE-marked system has recently been launched for an improved continuous flow blood separator (dideco Excel Pro) that contains a connection kit between the cell separator and a secondary filter and software which includes differential filtration as a standard protocol. The new system was used in our center using ethylenevinylalcohol secondary filters (Evaflux LA4 or LA5). 99 procedures were completed in 47 patients. A median of 2.7 (1.6-4.2) 1 of plasma were processed via the secondary filter in 109 (41-218) min. The values in peripheral blood before and after the treatment were total protein 6.7 (5.8-8.9)/ 5.3 (4.4-6.7) g/dl, fibrinogen 215 (118-480)/110 (37-275) mg/dl and cholesterol 200 (134-254)/92 (69 149) mg/dl. A median platelet loss of 30% in the peripheral blood of the patients was observed partly by platelet content of the separated plasma of 30 g/l after 500 ml of treatment and 10 g/l after 2,500 ml. Major side effects in the patients were not observed. The new differential filtration system already fulfills the demands of a ready-to-use CE-marked rheohemapheresis system but improvements in the details of the treatment protocol are still required and under way.

Adult↗

The role of rheology in hemapheresis.

Rheological therapy attempts to favorably influence the blood flow mechanics for the treatment of diseases, mainly of the microcirculation but also of the macrocirculation. Hemapheresis, originally used only for the elimination of an excess of cellular or plasmatic components, was shown to also influence the hemorheology favorably. As extracorporeal therapy affects the rheology much more than conventional hemorheotherapy, not only cellular or plasmatic hyperviscosity syndromes but also many more diseases associated with organ perfusion problems due to diseases of the micro- and macrocirculation, especially in the elderly, were and are increasingly considered to be indicated. Technical progress led away from plasma exchange as an unspecific and unselective procedure to plasma differential separation using precipitation. adsorption, and filtration. With our recent development, we demonstrated that rheohemapheresis is the most advanced technical procedure. The mechanism of action can well be related to a synergetic consideration of rheology. However. one has to keep in mind that the elimination of blood components such as lipids, immunoglobulins, and endothelial factors may well contribute to the explanation and understanding of the positive clinical effects observed. These speculative aspects need further investigation.

Adult↗

Effects of protein tyrosine kinase inhibitor genistein on retinal function in superfused vertebrate retina.

The aim of this study was to evaluate safe concentrations of genistein for a potential intraocular application using the isolated retina technique on bovine retina preparations. Bovine retinas were isolated and perfused with an oxygen pre-equilibrated standard solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver-chloride electrodes. After recording of stable ERG amplitudes, genistein was added to the solution in different concentrations. The percentage of b-wave reduction under the drug was calculated. We also studied the influence of genistein on the a-wave amplitude. After the addition of aspartate, the b-wave amplitude was reduced continuously until unmasked a-wave amplitudes were reached. Genistein was then added to the aspartate containing perfusate. The percentage of a-wave amplitude reduction under the drug was calculated. Concentrations of 3.3 microMol/l and higher were found to reduce the b-wave amplitude. The a-wave amplitude was not changed by the applied concentrations. The ERG only showed toxic effects from genistein beyond concentrations that were found to inhibit endothelial cell growth in vitro. In previous studies, beneficial effects on trabecular meshwork cells were present for genistein concentrations which are distinctly higher than the maximum nontoxic concentration reported here. It was shown that the photoreceptor layer is not affected at the examined concentration range. Therefore, we attribute the toxic effects to postsynaptic interaction of genistein. Intraocular application of genistein in a sufficient concentration seems possible.

Animals↗

The suitability of the ultrasound biomicroscope for establishing texture in giant cell arteritis.

AIM: To establish whether ultrasound biomicroscope (UBM) is a helpful tool in locating the arterial segment responsible in patients with segmental attacks in giant cell arteritis METHODS: The superficial temporal arteries of 19 patients with suspected giant cell arteritis were examined with the UBM before biopsy. RESULTS: 20 specimens provided the histological proof of giant cell arteritis in five patients. Side differences, a dark perivascular halo, and high reflexivity of the intra-arterial space were found. CONCLUSION: it is assumed that there are two types of arteritic inflammation: (1) the occlusion of intra-arterial space due to intimal fibrosis (UBM: high reflexive "filling"), and (2) inflammation of the perivascular zone with oedematous thickening and infiltration of the media (UBM: dark halo) and its combination. UBM is helpful in obtaining an indication of the side and segment for biopsy.

Aged↗

A Definitive Optical Detection of a Supercluster at z approximately 0.91.

We present the results from a multiband optical imaging program that has definitively confirmed the existence of a supercluster at z approximately 0.91. Two massive clusters of galaxies, Cl 1604+4304 at z=0.897 and Cl 1604+4321 at z=0.924, were originally observed in the high-redshift cluster survey of Oke, Postman, & Lubin. They are separated by 4300 km s-1 in radial velocity and 17&arcmin; on the plane of the sky. Their physical and redshift proximity suggested a promising supercluster candidate. Deep BRi imaging of the region between the two clusters indicates a large population of red galaxies. This population forms a tight, red sequence in the color-magnitude diagram at (R-i&parr0; approximately 1.4. The characteristic color is identical to that of the spectroscopically confirmed early-type galaxies in the two member clusters. The red galaxies are spread throughout the 5 h-1 Mpc region between Cl 1604+4304 and Cl 1604+4321. Their spatial distribution delineates the entire large-scale structure with high concentrations at the cluster centers. In addition, we detect a significant overdensity of red galaxies directly between Cl 1604+4304 and Cl 1604+4321 which is the signature of a third, rich cluster associated with this system. The strong sequence of red galaxies and their spatial distribution clearly indicate that we have discovered a supercluster at z approximately 0.91.

Journal Article↗

[Tibial torsion deformities].

Tibial torsion defects are usually not clinically evident and, hence, are often overlooked. Clinical examination and CT scan have proved to be the best ways of measuring static tibial torsion, whereas dynamic measurements are usually performed in the clinic and the "gait laboratory." Only few studies have determined there to be a connection between a torsion defect in the lower leg and expected pathological conditions of the knee and ankle joints. However, patellofemoral instability, Osgood-Schlatter disease, osteochondrosis dissecans are increasingly being found in cases of increased external tibial torsion and arthrosis in reduced torsion. Although spontaneous correction may occur in certain cases, in others the only way to correct the condition is by employing physiologic torsion. Conservative treatment methods such as bandages or orthosis have been shown to not have any effect on torsion; thus, surgical treatment is the only successful way to correct a pathologic angle of rotation of the tibia. For this, supramalleolar osteotomy with fixation using Kirscher wires and plaster or an external fixator are the most common treatments.

Adolescent↗

[Torsion deformities in the lower extremities in patients with infantile cerebral palsy: pathogenesis and therapy].

Patients with spastic cerebral palsy often develop torsional deformities at the level of hip, shank or foot. The abnormal muscle activity such as spasticity or the increase of tone are considered as the major cause. The present study shows that the gait pattern is another cause which may lead to deformities. The study is based on gait analysis of 13 patients and 8 normal controls. The major and significant differences in gait kinematics were toe walking, toeing-in and internal rotation at the hip in the patients whereas the unaffected control group had a physiological heel-toe gait. The difference in torsional moments at the hip, knee and ankle were statistically significant. At the knee and the ankle a decrease in the internal rotation moment was found, whereas at the hip a paradoxical curve pattern with a more externally directed rotation moment was seen. These differences in torsional moments can explain the external rotation at the foot and/or shank as well as the increase in femoral anteversion, although they might be primarily caused by the deformity itself. Because a constantly acting force, however, changes the bony form and/or shape, the abnormal moments can be considered as a factor leading to deformities. A heel-toe gait seems to be mandatory for an efficient prophylaxis. Torsional deformities at the shank require a corrective osteotomy which is performed at the supramalleolar site and fixed by an unilateral, external fixator. Malrotations at the hip usually show two components: the functional part can be corrected by lengthening and weakening the tensor fasciae latae and the ventral parts of the glutei, using stretching exercises, botulinum toxin A or operative lengthening and releases. The increased femoral anteversion needs to be corrected by a femoral derotation osteotomy. Patients with cerebral palsy show a reduced control of their legs; therefore, balance internal torsion should not be corrected to neutral and overcorrection must be avoided. A remaining slight internal rotation after correction will help to spontaneously stabilize the leg if it gives way at initial contact, by "falling underneath the centre of gravity". If the leg is in neutral or external rotation, the patient needs to realign the centre of gravity over the dynamically unstable leg, showing a trunk-lean over the leg, the Duchenne limp.

Adolescent↗

Near-field scanning optical microscopy of zinc-porphyrin crystals.

Using a near-field scanning optical microscope (NSOM), crystals of zinc-porphyrin network materials are characterized with respect to morphology and fluorescence. Needle-shaped crystals are observed. While the topography is flat, the fluorescence intensity profile in the width direction is approximately triangular. A numerical calculation shows that differences between the topographic and optical images cannot be due to an artifact. In some needle-shaped crystals, the fluorescence emission is strongly peaked at one or both ends, possibly indicating a polar crystal structure.

Crystallization↗

Acute and long-term effects on muscle force after intramuscular aponeurotic lengthening.

Intramuscular aponeurotic lengthening of muscles or intramuscular tenotomy involves bisecting the connective tissue fibers of the aponeurosis or tendon within the muscle belly. Because of its superficial location in the muscle, the aponeurosis may be bisected without damaging muscle fibers. Despite the existence of common operative methods for gaining length in short muscles, the effects on force and muscle function have not been studied. For this purpose animal experiments were performed. The medial gastrocnemius muscle of six male Wistar rats was lengthened by cutting the proximal aponeurosis at 50% of its length perpendicularly to the collagen fibers. The length gain was maintained by 3 days of cast immobilization at maximal dorsiflexion of the ankle. The long-term effect of the treatment was studied after 6 weeks and compared with 10 untreated controls and with six sham operated animals. The muscle was isolated in situ, and the force length characteristics were determined. In the untreated controls, the aponeurotomy was performed and the length force experiment was repeated to study the acute effects. The aponeurotic lengthening led acutely to a temporary loss of force because of an incomplete connection of the distal part of the muscle to the proximal insertion, but force recovered completely within 6 weeks. Although results from animal experiments cannot be transferred directly to humans, the principles of physiology are similar. Thus, for clinical use, aponeurotic lengthening should be considered if muscle force needs to be preserved. However, the drop of muscle force after surgery must be respected when mobilizing the patient during the postoperative rehabilitation program.

Animals↗

Dissociative symptomatology and traumatogenic factors in adolescent psychiatric patients.

This study describes the relation of different types of childhood trauma to the degree of dissociative experiences. Subjects were 198 consecutively admitted adolescent psychiatric patients, 11 to 19 years old (89 inpatients and 109 outpatients). All patients completed the Adolescent Dissociative Experiences Scale. A Checklist of Traumatic Childhood Events was filled out by clinicians. The results showed an increase in the degree of dissociative experiences in patients with a history of sexual abuse, physical abuse, neglect, and stressful life events. With the exception of life events, a moderate form of traumatic experience had the same effect on dissociative experiences as severe forms. The strongest effect was found for emotional neglect, which seems to be an important pathogenic risk factor. The results suggest that therapists and researchers should be aware that even less severe forms of abuse and neglect may have a significant impact on the development of dissociative psychopathology in adolescents.

Adolescent↗

Influence of membrane differential filtration on the natural course of age-related macular degeneration: a randomized trial.

PURPOSE: Membrane differential filtration is able to optimize rheologic parameters by eliminating high molecular weight proteins and lipoproteins from the blood. Following the hypothesis that these changes result in an improvement of the microcirculation, the authors tested the efficacy of membrane differential filtration in improving visual function in patients with age-related macular degeneration (ARMD). METHODS: Forty patients (40 eyes) were randomized into two groups. The treatment group was treated five times over a period of 21 weeks. In both groups, 9/20 of the eyes showed subfoveolar subretinal neovascularization. The main parameter of the study was visual acuity (VA). Electroretinogram (ERG), electrooculogram, and macular visual evoked potentials were also recorded. Plasma and whole blood viscosity and erythrocyte aggregation were measured. RESULTS: The 20 patients treated repeatedly over a period of 21 weeks showed a mean improvement of 0.63 lines (SD 1.8) of VA on Early Treatment Diabetic Retinopathy Study charts. The control group showed a deterioration of 0.94 lines (SD 1.7) compared to VA at baseline examination. The amplitude of the ERG photopic a-wave and the flicker ERG was significantly increased. The rheologic parameters were lowered in all treated patients. CONCLUSION: Repetitive treatment with membrane differential filtration is able to improve visual acuity of patients with ARMD and the natural course of this disease. Several questions arise from the results of this study. Further research will show if it is possible to optimize the selection of patients for subgroups with predictive responses through morphologic and functional tests and how to create an optimized and individual treatment strategy determined by the quality, intensity, and frequency of treatment sessions.

Aged↗

The structure of chromatophores from purple photosynthetic bacteria fused with lipid-impregnated collodion films determined by near-field scanning optical microscopy.

Lipid-impregnated collodion (nitrocellulose) films have been frequently used as a fusion substrate in the measurement and analysis of electrogenic activity in biological membranes and proteoliposomes. While the method of fusion of biological membranes or proteoliposomes with such films has found a wide application, little is known about the structures formed after the fusion. Yet, knowledge of this structure is important for the interpretation of the measured electric potential. To characterize structures formed after fusion of membrane vesicles (chromatophores) from the purple bacterium Rhodobacter sphaeroides with lipid-impregnated collodion films, we used near-field scanning optical microscopy. It is shown here that structures formed from chromatophores on the collodion film can be distinguished from the lipid-impregnated background by measuring the fluorescence originating either from endogenous fluorophores of the chromatophores or from fluorescent dyes trapped inside the chromatophores. The structures formed after fusion of chromatophores to the collodion film look like isolated (or sometimes aggregated, depending on the conditions) blisters, with diameters ranging from 0.3 to 10 microm (average approximately 1 microm) and heights from 0.01 to 1 microm (average approximately 0.03 microm). These large sizes indicate that the blisters are formed by the fusion of many chromatophores. Results with dyes trapped inside chromatophores reveal that chromatophores fused with lipid-impregnated films retain a distinct internal water phase.

Bacterial Chromatophores↗

MRP expression in acute myeloid leukemia. An update.

To determine the clinical significance of the multidrug resistance protein (MRP) in patients with de novo AML, we have studied MRP expression of leukemic cells at diagnosis and its association with clinical outcome in 127 patients. MRP expression was determined by immunocytochemistry by means of monoclonal antibodies QCRL-1/QCRL-3. MRP expression was low, intermediate and high in 30%, 46% and 24% of the patients, respectively. MRP expression was independent of age and sex of the patients, white blood cell count, FAB subtype, serum lactate dehydrogenase levels and karyotype aberrations. MRP expression had no impact no response to induction chemotherapy. The complete remission rates were 75%, 70% and 64% for patients with low, intermediate and high expression, respectively. Patients with intermediate or high MRP expression showed a trend toward shorter overall survival (p = 0.09) as compared to patients with low MRP expression. MRP does not predict for response to induction chemotherapy but intermediate or high MRP expression might be associated with shorter overall survival of the patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗