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Biomedical subjects

M Siebert

Publications and source records attributed to M Siebert.

At least 37 records · Page 2Linked to original sources
PubMed1999

Technical developments in intra-operative monitoring for the preservation of cranial motor nerves and hearing in skull base surgery.

Although EMG recordings from mimic muscles have become the standard for intra-operative facial nerve monitoring, few data are available concerning other motor cranial nerves (MCN). Auditory brainstem responses (ABR) are a proven tool for intra-operative hearing preservation, but have their limitations, suggesting the application of supplementary methods. This paper describes new developments of MCN and cochlear nerve monitoring in skull base surgery. Up to 2 x 8 EMG channels were recorded after bipolar stimulation of MCN using concentric coaxial probes. A special software enabled event-dependent registrations of all signals exceeding a definable threshold level. Selective recordings from masticatory muscles (N.V) were obtained using rectangular Teflon-insulated needle electrodes. For oculomotor (Nn.III/ VI) nerve recordings bipolar needle electrodes were precisely placed by orbital ultrasound guidance. Lower cranial nerves were monitored inserting needle electrodes into the soft palate (N.IX), tongue (N.XII) and vocal muscles (N.X) during laryngoscopy using a special applicator. For ABR recordings, click stimuli (95 dB HL) were applied monaurally through insert earphones. Electrocochleography was simultaneously recorded as a near-field potential without averaging after promontory (transtympanic) electrode placement using otomicroscopy. Regarding the ABR biosignal, a characteristic response pattern was detected following bipolar electrical stimulation of the auditory nerve possibly useful for its intra-operative identification.

Cochlear Nerve↗
PubMed1997

Identification of novel graded polarity actin filament bundles in locomoting heart fibroblasts: implications for the generation of motile force.

We have determined the structural organization and dynamic behavior of actin filaments in entire primary locomoting heart fibroblasts by S1 decoration, serial section EM, and photoactivation of fluorescence. As expected, actin filaments in the lamellipodium of these cells have uniform polarity with barbed ends facing forward. In the lamella, cell body, and tail there are two observable types of actin filament organization. A less abundant type is located on the inner surface of the plasma membrane and is composed of short, overlapping actin bundles (0.25-2.5 microm) that repeatedly alternate in polarity from uniform barbed ends forward to uniform pointed ends forward. This type of organization is similar to the organization we show for actin filament bundles (stress fibers) in nonlocomoting cells (PtK2 cells) and to the known organization of muscle sarcomeres. The more abundant type of actin filament organization in locomoting heart fibroblasts is mostly ventrally located and is composed of long, overlapping bundles (average 13 microm, but can reach up to about 30 microm) which span the length of the cell. This more abundant type has a novel graded polarity organization. In each actin bundle, polarity gradually changes along the length of the bundle. Actual actin filament polarity at any given point in the bundle is determined by position in the cell; the closer to the front of the cell the more barbed ends of actin filaments face forward. By photoactivation marking in locomoting heart fibroblasts, as expected in the lamellipodium, actin filaments flow rearward with respect to substrate. In the lamella, all marked and observed actin filaments remain stationary with respect to substrate as the fibroblast locomotes. In the cell body of locomoting fibroblasts there are two dynamic populations of actin filaments: one remains stationary and the other moves forward with respect to substrate at the rate of the cell body. This is the first time that the structural organization and dynamics of actin filaments have been determined in an entire locomoting cell. The organization, dynamics, and relative abundance of graded polarity actin filament bundles have important implications for the generation of motile force during primary heart fibroblast locomotion.

Actin Cytoskeleton↗
PubMed1997

An evaluation of salmeterol in the treatment of chronic obstructive pulmonary disease (COPD)

The objectives of this study were to compare the efficacy and safety of salmeterol xinafoate (50 and 100 microg b.i.d.) with that of placebo, when added to existing therapy, in the treatment of patients with chronic obstructive pulmonary disease (COPD). Six hundred and seventy four patients were randomized to receive either salmeterol 50 microg b.i.d., salmeterol 100 microg b.i.d., or placebo treatment for a period of 16 weeks. The results showed a significant improvement in daily symptom scores noted for patients taking either 50 microg (p=0.043) or 100 microg b.i.d. salmeterol (p=0.01) compared with placebo, with a corresponding decrease in additional daytime salbutamol requirements for both salmeterol groups. The same pattern was reflected for night-time symptoms and additional salbutamol use. During treatment, forced expiratory volume in one second (FEV1) measurements improved significantly in each salmeterol group, with up to a 7% improvement observed at the end of the study. Although no difference was observed between treatment groups for the distance walked in 6 min, patients treated with salmeterol 50 microg b.i.d. were significantly less breathless than those treated with placebo after their 6 min walk, after 8 weeks (p=0.024) and 16 weeks (p=0.004) of therapy. Adverse events were similar in all three groups except for tremor, which was significantly higher in the 100 microg b.i.d. salmeterol group (p=0.005) compared both with 50 microg b.i.d. salmeterol and placebo. Salmeterol offered further positive improvement to the effect of therapy in patients with chronic obstructive pulmonary disease when added to their existing regimens. This clinical improvement was similar both with 50 and 100 microg b.i.d. dosage, although the group receiving 50 microg b.i.d. tolerated the drug better than those receiving 100 microg b.i.d. salmeterol.

Adult↗
PubMed1996

Genetic engineering of plant secondary metabolism. Accumulation of 4-hydroxybenzoate glucosides as a result of the expression of the bacterial ubiC gene in tobacco.

The ubiC gene of Escherichia coli encodes chorismate pyruvatelyase, an enzyme that converts chorismate into 4-hydroxybenzoate (4HB) and is not normally present in plants. The ubiC gene was expressed in Nicotiana tabacum L. plants under control of a constitutive plant promoter. The gene product was targeted into the plastid by fusing it to the sequence for the chloroplast transit peptide of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase. Transgenic plants showed high chorismate pyruvate-lyase activity and accumulated 4HB as beta-glucosides, with the glucose attached to either the hydroxy or the carboxyl function of 4HB. The total content of 4HB glucosides was approximately 0.52% of dry weight, which exceeded the content of untransformed plants by at least a factor of 1000. Feeding experiments with [1,7-13C2]shikimic acid unequivocally proved that the 4HB that was formed in the transgenic plants was not derived from the conventional phenylpropanoid pathway but from the newly introduced chorismate pyruvate-lyase reaction.

Amino Acid Sequence↗
PubMed1995

[Comparison of the measurement values of the laser tomography scanner and optic nerve head analyzer. A clinical study].

INTRODUCTION: With the Laser Tomographic Scanner (LTS) and the Optic Nerve Head Analyzer (ONHA) a quantifying investigation of the optic disc is possible. Both work with different principles: The LTS receives the information about the three dimensional structure with 32 transversal cuts, taken with the confocal principle, the ONHA with simultan stereopictures, taken from a different point of view. PATIENTS AND METHODS: We examined 36 eyes (18 patients) with the LTS and the ONHA. The aim of the study is to examine, whether there are differences in the measurement values taken with the LTS and the ONHA investigating the same optic disc. RESULTS: 1. There are no significant differences in the measurement value of the area of the total disc and the horizontal and vertical diameter of the optic disc. 2. The measurement values of the area of the excavation and the quotient of the area of excavation to the area of the total disc are systematically greater in investigation with the LTS than in investigation with the ONHA. This is explained by the different definition of the boundary of the excavation. 3. There are significant differences in the measurement values of the volume of the excavation, the upper volume of the optic disc, and the maximum depth of the excavation. The measurement value of the volume of the excavation is systematically greater in investigation with the ONHA than in investigation with the LTS. CONCLUSION: Measurement values of the parameters of the optic disc, which have the same definition in the LTS and the ONHA--such as the area of the total disc and the horizontal and vertical diameter of the optic disc--show no significant differences. Thus these parameters are comparable in the LTS and the ONHA.

Glaucoma↗
PubMed1995

[High mean pallor value--a risk factor for deterioration of the visual field in glaucoma and ocular hypertension. A pilot study using the optic nerve head analyzer].

UNLABELLED: Does the disc parameter "mean pallor value" suggest a risk for further deterioration of visual field defects? PATIENTS: In 10 patients with ocular hypertension and 23 patients with primary open-angle glaucoma (Octopus 201, Humphrey perimeter) disc pallor was calculated by double examinations with the ONHA in 1987-1988, and a long-term follow-up of the visual field was performed. In all patients we also acquired information about the IOP level and visual field during the observation time from the ophthalmologists. Only one eye per patient was evaluated after randomized selection. RESULTS: In ocular hypertensive patients only 1 of 10 eyes showed deterioration of the visual field. In the glaucoma group 4 eyes out of 23 showed an increase in visual field loss. The eyes with a tendency to deteriorate had a higher mean pallor value compared with the mean value of the corresponding group [ocular hypertensives: 0.40 compared to 0.31 +/- 0.07 (0.02); POAG: 0.50 +/- 0.06 (0.03) compared to 0.33 +/- 0.08 (0.02); mean value +/- SE (SEM)]. The difference was statistically significant in the glaucoma group; Wilcoxon, Mann and Whitney U-test; P < 0.005. CONCLUSIONS: Taking into consideration all risk factors, the mean pallor value might help additionally to prognosticate the risk of deterioration of the visual field as far as 5-year follow-up allows this preliminary conclusion. The pallor value alone is not suitable for the follow-up of glaucoma patients because of the influence of increasing lens opacities and changes in the video system of the ONHA over years.

Follow-Up Studies↗
PubMed1994

Formation of 4-hydroxybenzoate in Escherichia coli: characterization of the ubiC gene and its encoded enzyme chorismate pyruvate-lyase.

Chorismate pyruvate-lyase from Escherichia coli converts chorismate to 4-hydroxybenzoate. The enzyme was enriched 3000-fold by overexpression and chromatographic purification. It has an apparent Km value for chorismate of 6.1 microM and an isoelectric point of pH 6.45. The enzyme activity did not require metal cofactors. Promoter sequences in the 5' flanking sequences of the ubiCA operon were localized by transcription and translation of active chorismate pyruvate-lyase in vitro from different PCR fragments. Sequencing of the ubiC gene of the mutant strain AN244 revealed a G-->A transition resulting in a change from glutamic acid to lysine. A feeding experiment with [1,7-13C2]shikimate confirmed the chorismate pyruvate-lyase as the sole enzymic source of 4-hydroxybenzoate in vivo.

Bacterial Proteins↗
PubMed1992

Ubiquinone biosynthesis. Cloning of the genes coding for chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyl transferase from Escherichia coli.

Chorismate pyruvate-lyase activity was detected in extracts of Escherichia coli. 4-Hydroxybenzoate was identified as the product of the enzymatic reaction by chemical derivatization and GC-MS analysis. The ubiC gene, coding for the chorismate pyruvate-lyase, was cloned and sequenced. The molecular weight of the gene product was calculated as 18,776 Da and confirmed by expression of the protein in E. coli minicells. The ubiA gene, coding for the 4-hydroxybenzoate octaprenyl transferase, was identified by sequence homology and complementation of a ubiA- strain. It is located directly downstream of ubiC in a typical operon structure.

Alkyl and Aryl Transferases↗
PubMed1991

[Sensitivity of noise field campimetry as a screening method for glaucoma].

The glaucoma patient can perceive his or her visual field loss subjectively with snow field campimetry with the Tübingen electronic campimeter (TEC). The sensitivity of this new method of examination for glaucoma has not previously been evaluated. We were interested in finding whether absolute and relative scotomas could be detected with such high probability that snow field campimetry could be used as a screening method for the early detection of glaucoma. Analysis of the severity of scotoma is not possible, so that snow field perimetry can indeed by regarded as a screening procedure. A total of 76 eyes of 76 patients with glaucoma and stage I-IV visual field loss and 20 eyes of 20 patients with ocular hypertension were examined with threshold determining static perimetry (Octopus or Humphrey perimeter) and with the snow field of the TEC in controlled conditions. A qualitative comparison was drawn to evaluate how often a pathologic or normal finding was confirmed by snow field campimetry: of the 76 eyes affected by scotoma, 65 eyes (85.5%) showed pathologic findings consistent with the result of snow field campimetry, and 11 eyes showed normal findings. The visual field loss was 63.6% for glaucomatous visual field loss stage I: 90.9% for glaucomatous visual field loss stage II, and 95% for visual field loss stages III and IV. For 16 of the 20 eyes with ocular hypertensions normal findings were reported with snow field campimetry. Snow field campimetry is suitable for use as a quick screening procedure, but only for absolute glaucomatous scotomas.

Adult↗
PubMed1990

Development of monoclonal antibodies for therapeutic drug monitoring.

For the development of multilayer fluorescent immunoassays to determine directly a variety of therapeutic drugs high specific monoclonal antibodies against the anticonvulsants carbamazepine, phenobarbital, phenytoin and valproic acid have been prepared. For each antibody a standard curve could be established showing good linearity and a suitable sensitivity scope. To validate the eligibility of the desired antibodies a variety of drugs and metabolites sharing structural similarities to the individual drugs were tested for their cross-reactivity. It could be shown that only a few very closely related compounds exhibited substantial cross-reactivity. These monoclonal antibodies are therefore assumed to be suitable for a TDM-assay development.

Antibodies, Monoclonal↗
PubMed1989

Optic nerve head measurements: the optic nerve head analyzer--its advantages and its limitations.

The Optic Nerve Head Analyzer (ONHA) calculates by means of computer-assisted analysis of stereo images different parameters of the optic disc: disc diameter, disc size, cup/disc ratio (CDR), neuroretinal rim area, and excavation volume for the disc quadrants and for the total disc. To obtain first indications of the clinical value of ONHA measurements for diagnosis and follow-up in glaucoma we examined the reproducibility of measurement results for different diseases. Furthermore, we studied the mean values of the different disc parameters in healthy eyes. It was investigated: 1) whether the reproducibility is different in the different disc parameters; 2) whether the reproducibility in different eye diseases is different as compared to healthy eyes; 3) by which criteria the reproducibility is influenced; 4) whether there is a correlation between disc size and size of rim area. The reproducibility was studied in 178 eyes of 178 patients, who were all examined twice with the ONHA. The mean difference between the results of first and second measurement was calculated for the different disc parameters. Differences were found in the reproducibility of the parameters: e.g., the mean difference between first and second measurement was 1.8 percent for the disc size, and 5.6 percent for the neuroretinal rim area. For the disc quadrants, the reproducibility of values was worse than for the total disc. No marked differences of reproducibility of disc parameters were found for different diseases. Reproducibility depends, for instance, upon correct determination of the disc margin. In healthy eyes, a significant correlation was found between rim area and disc size: larger discs have a larger neuroretinal rim area than smaller discs. Thus, the rim areas of different eyes are only comparable for equally sized discs. Relative values, as for instance, cup/disc ratio, or the quotient of rim area and disc size, are therefore better suited for comparison of different eyes than absolute values. The recent developments in automatic disc analysis equipment and the clinical relevance of the results for diagnosis and follow-up in glaucoma are discussed.

Diagnosis, Computer-Assisted↗
PubMed1989

[The prospective value of Doppler blood flow measurement in uteroplacental and fetal blood vessels--a comparative study of multiple parameters].

Doppler blood flow parameters of uteroplacental and fetal vessels (umbilical artery, fetal aorta, fetal common carotid artery) were tested to determine their clinical value in predicting IUGR or fetal hypoxia, considering the time interval from the examination to the delivery. More than 2 weeks before the delivery, only Doppler parameters of uteroplacental vessels revealed a sensitivity of detecting IUGR of above 50%, using the resistance index. In the last two weeks before the delivery, there was a significant increase of the clinical value of fetal blood flow parameters. The sensitivity of the ratio of the mean blood flow velocity of the fetal common carotid artery to the fetal aorta with a view to detecting a pathological CTG was 94% with a specificity of 60%. In summary, we conclude that blood flow parameters of uteroplacental vessels can be used for screening examinations. Blood flow parameters of fetal vessels are indicated for the supervision of risk pregnancies. The redistribution of the fetal circulation is reflected in the ratio of blood flow parameters of the common carotid artery to the umbilical artery or to the fetal aorta. These parameters seem to be helpful for the early detection of imminent fetal hypoxia in cases with risk pregnancy. Even when a suspicious or pathological CTG does not allow an exact diagnosis of fetal hypoxia, this does not change the basic meaning of this study.

Blood Flow Velocity↗
PubMed1989

[Pallor of the optic papilla--an early sign of glaucoma. A clinical controlled study of optic disk pallor and papillar cupping in glaucoma simplex, ocular hypertension and normal eyes with the optic nerve head analyzer].

Double examinations of 99 eyes (34 healthy, 12 with ocular hypertension, 53 with primary open-angle glaucoma) were performed with the Optic Nerve Head Analyzer to evaluate whether an increase in disk pallor or in the cup-disk ratio (CDR) is the earlier sign of glaucoma. In eyes with primary open-angle glaucoma the CDR and the mean optic disk pallor value are significantly higher than in healthy eyes. There is no significant difference in the CDR of patients with ocular hypertension as compared to normals. However, the mean pallor value is significantly higher in eyes with ocular hypertension than in healthy eyes. Therefore, an increase in pallor may precede a significant increase in the CDR or detectable visual field defects.

Glaucoma, Open-Angle↗
PubMed1988

An in vivo study on the synchronizing effect of hydroxyurea.

The effect of hydroxyurea (HU; 0.5 mg/g body wt) on L 1210 ascites tumor cells has been studied using various cell kinetic methods. In contrast to the general assumption that HU blocks cells at the G1/S boundary [J. Brachet (1985) Molecular Cytology, Vol. I, p. 266, Academic Press, New York], the present results show that the cells are not held at G1/S but enter S at about the normal rate and are accumulated in early S phase due to a dose-dependent inhibiting effect of HU on DNA synthesis. Partial synchronization of the cells demonstrated by a distinct mitotic peak 10 h after HU application is not due to a G1/S block of the cells and their subsequent synchronous passage through the cycle after release from the block but is due to rather complex mechanisms of action of HU: a differential cytocidal effect and an effect on the passage of the cells through the cycle, both depending on the position of the cells throughout the cycle. HU kills S-phase cells, mainly cells in early S phase; i.e., a great portion of the cells "accumulated" in early S phase is killed by the drug, while G1-phase cells are almost not affected by the lethal effect of HU. These G1-phase cells pass through the cycle more rapidly after cessation of the HU effect. The same is true for the surviving cells accumulated in early S phase, while part of the cells in the remaining S phase are delayed in their passage through the cycle. This causes partial synchronization, since a great portion of all cells that survive HU treatment reach mitosis at the same time.

Animals↗
PubMed1988

[Optic papilla parameters in healthy subjects--quantified with the optic nerve head analyzer].

The cup-disk ratio (CDR), the size of the neuroretinal rim area as well as the other disk parameters investigated with the Optic Nerve Head Analyzer (ONHA) were measured in double examinations of 32 healthy eyes in 32 patients. Thus, "normal" values were determined for the various disk parameters. A new method is presented for calculating one average pallor value for the disk. The mean value for disk pallor in healthy eyes is determined. Examination of the CDR in the quadrants of the disk reveals significant differences. According to the results of a multi-regressional analysis of the various disk parameters, the size of the neuroretinal rim area in healthy eyes is influenced by the size of the disk, the disk volume and the elevation volume. The correlation between the size of the neuroretinal rim area and the size of the disk reveals a significant interdependence: a larger disk also has a greater neuroretinal rim area as compared to a smaller disk. This means that sizes of neuroretinal rim areas of different disk should only be compared when the disks are the same size. Relative values, such as the CDR or the ratio between the size of the neuroretinal rim area and disk size (rim area/disk area), are therefore better suited for comparison.

Humans↗
PubMed1988

Obstetrical characteristics of a loss of end-diastolic velocities in the fetal aorta and/or umbilical artery using Doppler ultrasound.

In 30 of 137 high-risk pregnancies we observed absent end-diastolic velocities indicating a high downstream impedance, which could be proved by histomorphological findings of the placenta. On the average the loss of end-diastolic velocities occurred 2-3 days before suspicious and nearly 8 days before pathological cardiotocographic findings. The perinatal mortality was high when absent velocities had been observed before the 32nd week, a cesarean section was obligatory in all but 1 case. All fetuses were growth-retarded. In 9 cases we were able to determine the ratio of blood flow volume in the common carotid arteries to that of the fetal aorta. The values were significantly increased as compared to values of undisturbed pregnancies, demonstrating a redistribution of fetal blood in favor of cerebral circulation.

Aorta↗