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Biomedical subjects

M Hahn

Publications and source records attributed to M Hahn.

At least 181 records · Page 10Linked to original sources

Three-dimensional analysis of the spine in autopsy cases with renal osteodystrophy.

The spinal column was removed from nine autopsy cases with chronic maintenance dialysis and sectioned in the sagittal plane to a thickness of 1 millimeter using a surface-stained block grinding technique. A combination of two- and three-dimensional analysis included an evaluation of the spine deformity index (SDI), the bone volume (BV/TV), the trabecular interconnection (TBPf), the trabecular thickness (Tb.Th), the trabecular number (Tb.N) as well as a qualitative investigation of the structure of cancellous bone. The control group consisted of 26 autopsy cases with intact skeletons. An iliac crest biopsy made a direct comparison of the diagnostic biopsy location and the spinal column possible. The SDI showed vertebral fractures in renal osteodystrophy (ROD) of types I and II, in spite of a trabecular bone volume within normal limits. The trabecular bone volume showed mean values and a distribution throughout the spinal column familiar in the skeletally-intact control group. Those cases with a longer history of hemodialysis showed higher BV/TV values regardless of age and sex. A trabecular volume within normal limits did not mean physiological trabecular interconnection. Perforations were commonly observed with ROD. Classical, hidden and tunnelling perforations were distinguished. Microcallus formations were frequently seen in the periphery of vertebrae at rod nodes, rods and plate intersections. Three-dimensional analysis in ROD shows a greater alteration in architecture than can be assumed from the two-dimensional histological sections.

Autopsy↗

The microarchitecture of the axis as the predisposing factor for fracture of the base of the odontoid process. A histomorphometric analysis of twenty-two autopsy specimens.

The axis from twenty-two cadavera was removed at autopsy and was sectioned in the sagittal plane to a thickness of one millimeter with use of a surface-stained block-grinding technique. Combined two and three-dimensional analysis included an evaluation of the volume of the trabecular bone, the trabecular interconnection, and the cortical thickness as well as qualitative investigation of the structure of the cancellous bone. The body of the axis, the base of the odontoid process, and the odontoid process were analyzed separately. The base of the odontoid process is a region of least resistance for fractures because of its unique microarchitecture. The mean volume of trabecular bone of the base of the odontoid process is 55 per cent less than that of the axis and the odontoid process. The base also has a markedly poorer trabecular interconnection and a cortical thickness that is one-third that of the odontoid process. In all of the specimens, trabeculae that were disconnected from the trabecular lattice (trabeculae with free ends) were demonstrated in the base of the odontoid process. The formation of microcallus in six (27 per cent) of the specimens supports the hypothesis that microfractures occur as a result of stress peaks, mechanical fatigue, and the relative insufficiency of bone in the static condition. Therefore, the base of the odontoid process can be considered as a site of predilection for fractures.

Adolescent↗

Evaluation of conventional press-and-breathe metered-dose inhaler technique in 501 patients.

Conventional press-and-breathe metered dose inhalers (MDIs) are widely prescribed but are often difficult for many patients to properly use. A total of 501 patients from different medical specialties were enrolled in this study, which evaluated how the patients used their MDIs. Using a conservative method (minimum number of errors) of determining errors, we found that 388 (77.5%) of the patients made at least one error when demonstrating how they use their MDI for two observers. Using a liberal (maximum number of errors) method of analysis, we found that 447 (89.2%) of the patients made at least one error. There was no difference in errors made stratified by patient gender, patient age, or the medical specialty that treated the patient's pulmonary disease. The two most common errors made by patients were failure to breathe out to functional residual capacity before actuation (225 by minimum method, 280 by maximum method) and not actuating the canister at the start of inhalation (207 by minimum method, 323 by maximum method). Of the patients with improper timing of actuation, the majority (121 patients by minimum method and 187 patients by maximum method) actuated the canister early. In this large patient sample, regardless of which medical specialty provided the treatment, the majority of the patients evaluated had less than optimal MDI technique. Routine assessment of MDI technique should be instituted as standard practice care.

Adolescent↗

[Intraoperative leg length measurement in total hip endoprosthesis].

Preservation or restoration of the equal length of both legs after total hip arthroplasty is best achieved by direct intraoperative measurement. The measuring instruments designed for this purpose are presented and their application described for the posterior approach to the hip. The instruments are easy and quick to use. They can also be used for other approaches to the hip and in addition they are a valuable aid when estimating the angles of anteversion and inclination of the acetabular component. The high degree of accuracy and the significant improvement in results when this instrument was used intraoperatively was confirmed by comparison of radiographic measurements of two operation series.

Anthropometry↗

[Structure of the axis--key to the etiology of the dens fracture].

Fractures of the dens are seen especially in young adolescents but also in individuals after the sixth decade of life. The etiology of these fractures and the occurrence of non-union after initial treatment is still discussed controversially. To address these issues, the axis was removed from thirty-seven autopsy cases for histomorphometric analysis. The base of the dens is a region of least resistance for fractures due to its reduced trabecular bone volume, a poorer trabecular interconnection and a cortical thickness one third that of the axis. In all of the cases, trabeculae disconnected from the trabecular lattice, and in 30% microcallus formations were demonstrated in the base of the dens. In osteoporotics the microarchitectural differences of cancellous bone between the base of the dens and the other regions of the axis are increased markedly. The obtained data suggest that the bone structure of the axis is responsible for the location, the distribution and the frequency of fractures of the odontoid process. The deficiency of bone mass within the base also offers a new explantation for the occurrence of non-unions even after treatment of fractures of the base of the dens.

Adolescent↗

[Significance of cutaneous microangiopathy for the pathogenesis of dermatitis in venous congestion due to chronic venous insufficiency].

Skin damage due to chronic venous insufficiency is preceded by severe microangiopathy of skin. With increasing clinical symptoms like edema, hyperpigmentation, induration, ulcer and atrophy blanche number of nutritive capillaries and transcutaneous oxygen-tension decreases, transcapillary, and interstitial leakage increases and cutaneous vascular reserve disappears. These congruent results were found by means of capillaroscopy, fluorescence-videomicroscopy, transcutaneously measured oxygen partial pressure and Laser Doppler Fluxmetry. Most of capillaries are elongated and tortuous, especially in ulcer stage they look glomerular. Compared to pin-shaped capillaries glomerular capillaries contribute less to nutrition because of functional AV-shunts. As dilated capillaries are already seen in skin areas without any trophic skin changes, cutaneous microangiopathy seems to be first consequence of venous hemodynamic disturbances which then is followed by skin disease. As severe microangiopathy still remains after healing of ulcer, it explains frequent recurrencies.

Blood Flow Velocity↗

Significant association of lipid peroxidation products with high density lipoproteins.

In this study the role of high density lipoproteins in lipoprotein peroxidation process was investigated. Under basal conditions, HDL isolated from human plasma or from total lipoprotein fraction (density > 1.21) using precipitation technique carried nearly 35-40% of the total plasma fatty acid peroxidation product (measured as malonaldehyde, MDA). HDL associated MDA was reduced to < 20% when HDL was isolated by ultracentrifugation from plasma treated with Cu++. Under these conditions, 45% of the cholesterol peroxidation products (oxysterols) were associated with HDL. HDL isolated from Cu++ treated plasma significantly lost its ability to inhibit LDL peroxidation. These results suggest that HDL plays an important role in lipid peroxidation a) by carrying significant amounts of cholesterol and lipid peroxidation products, and b) its ability to inhibit LDL oxidation is compromised when HDL itself is oxidized.

Blood↗

Quantitative polymerase chain reaction with oligodeoxynucleotide ligation assay/enzyme-linked immunosorbent assay detection.

Quantitation of nucleic acids by the polymerase chain reaction (PCR) requires coamplification of a control nucleic acid, usually a variant of the sequence to be analyzed, which is added to the sample DNA and amplified in competition. Following PCR, amplified sample and control DNAs are separated by electrophoresis and quantitated, for example by measuring the radioactivity incorporated into the products during the PCR. The need for both electrophoretic separation and radioactive labeling has considerably impeded the use of PCR for routine purposes, e.g., in the clinical laboratory, which requires automatic processing of many samples in parallel. We describe here a quantitative PCR procedure which circumvents electrophoretic separation and detection by radioactivity. It uses a point mutated version of the sample DNA as an internal control. After competitive PCR, amplified sample and control DNA are distinguished by an oligodeoxynucleotide ligation assay (OLA) (Landegren et al., Science 241, 1077-1080, 1988) using two oligodeoxynucleotides, one carrying a biotin-group at the 5'-end and another one with either a digoxigenin (specific for sample DNA) or fluorescein moiety (specific for control DNA), respectively, incorporated close to the 3'-end. Biotinylated oligodeoxynucleotides, educts as well as products of the ligation reaction, are immobilized on avidin-coated microtiter plates. Quantitation of digoxigenin and fluorescein-labeled oligodeoxynucleotide ligation products is achieved by an enzyme-linked immunosorbent assay. This method is very well suited for fast automated or semiautomated PCR.

Base Sequence↗

DNA helix structure and refinement algorithm: comparison of models for d(CCAGGCm5CTGG) derived from NUCLSQ, TNT and X-PLOR.

In an earlier study [Heinemann & Hahn (1992). J. Biol. Chem. 267, 7332-7341], the crystal structure of the double-stranded B-DNA decamer d(CCAGGCm(5)CTGG) was refined with NUCLSQ to R = 17.4% against 3799 2sigma structure amplitudes in the resolution range 8-1.7 A. This structure has now been re-refined against the same diffraction data using either TNT or X-PLOR in order to determine to what extent the resulting DNA conformations would differ and to examine the suitability of these programs for the refinement of oligonucleotide structures. The R value from the NUCLSQ refinement could not be reached with either TNT or X-PLOR, although both programs yield reasonably refined DNA models showing root-mean-square deviations against the NUCLSQ model of the decamer duplex of 0.25 and 0.32 A, respectively. Some derived local structure parameters differ depending on the refinement procedure used. This holds true for several exocyclic torsion angles of the sugar-phosphate backbone, whereas sugar puckers as well as helical and base-pair stacking parameters are only weakly influenced. A subset of 15 solvent sites with low temperature factors is conserved in all three models.

Journal Article↗

Human beta 2-adrenergic receptor produced in stably transformed insect cells is functionally coupled via endogenous GTP-binding protein to adenylyl cyclase.

Spodoptera frugiperda insect cells (Sf9) containing the stably integrated human beta 2-adrenergic receptor gene under the control of the baculovirus IE1 promoter expressed up to 350,000 human receptors/cell. The number of receptors did not change with cell density or age of culture. The adrenergic receptors overexpressed in the insect cells were functional with respect to their ligand binding and signalling properties. Coupling of the receptors to endogenous GTP-binding proteins is demonstrated by hormone-dependent stimulation of GTPase and adenylyl cyclase activity in the transformed insect cells. Western-blot analysis revealed that the endogenous GTP-binding protein appears to be of the heterotrimeric type. Antibodies raised against the mammalian alpha subunit of stimulatory GTP-binding proteins cross-react with the insect alpha subunit of GTP-binding proteins, which also exhibits the same apparent molecular mass as its mammalian counterpart. The beta subunit of GTP-binding proteins from insect cells reacts with anti-peptide serum directed against the C-terminal amino acids of the mammalian beta subunit of GTP-binding proteins, but is about approximately 2 kDa larger than that of the beta subunit of GTP-binding proteins from bovine brain. Exposure of the transformed insect cells to L-isoproterenol rapidly induces uncoupling and internalization of 30% of the heterologously expressed receptors. In contrast to the situation in mammalian cells, prolonged exposure of the agonist (24 h) does not result in down regulation of the remaining 70% of the receptors.

Adenylyl Cyclases↗

Pharmacokinetics of etoposide: correlation of pharmacokinetic parameters with clinical conditions.

The pharmacokinetic parameters of etoposide were established in 35 patients receiving the drug parenterally within the framework of different polychemotherapy protocols. A total of 62 data for 24-h kinetics were analysed. After sample extraction and high-performance liquid chromatography (HPLC) or thin-layer chromatographic (TLC) separation, etoposide was measured by means of [252Cf]-plasma desorption mass spectrometry (PDMS). This highly specific detection system proved to be very practicable and reproducible. The present study comprised two parts that were absolutely comparable in terms of clinical and pharmacokinetic parameters. In part II of the study, sensitivity was improved by modifying the analytical technique. After the exclusion of patients who had previously been given cisplatin or who exhibited renal impairment and of one patient who showed extremely high levels of alkaline phosphatase, gamma-GT and SGPT, the mean values calculated for the pharmacokinetic parameters evaluated were: beta-elimination half-life (t 1/2 beta), 4.9 +/- 1.2 h; mean residence time (MRT), 6.7 +/- 1.4 h; area under the concentration-time curve (AUC), 5.43 +/- 1.74 mg min ml-1; volume of distribution at steady state (Vdss), 6.8 +/- 2.7 l/m2; and clearance (Cl), 18.8 +/- 5.3 ml min-1 m-2. The pharmacokinetic parameters were correlated with 12 different demographic or biochemical conditions. Impaired renal function, previous application of cisplatin and the age of patients were found to influence etoposide disposition to a statistically significant extent. We suggest that the dose of etoposide should be reduced in elderly patients and/or in individuals with impaired renal function, especially in those exhibiting general risk factors such as reduced liver function with regard to the polychemotherapy.

Adult↗

A device for overcoming discoordination with metered-dose inhalers.

BACKGROUND: Despite widespread acceptance of metered-dose inhalers (MDIs) in the treatment of asthma, many patients fail to operate these devices correctly. Inability to properly coordinate activation with onset of inhalation is regarded as the major factor in suboptimal MDI therapy. METHODS: We evaluated Autohaler Inhalation Device (3M Pharmaceuticals, St. Paul, Minn.), a breath-activated MDI that is typically activated at a triggering flow rate of approximately 0.5 L/sec. We compared bronchodilator effect of pirbuterol acetate (Maxair), inhaled from Autohaler and a standard MDI, under conditions that ensured optimal technique in 20 patients with asthma. Spirometric variables (forced expiratory volume in 1 second [FEV1], forced expiratory flow between 25% and 75% of vital capacity [FEF25-75], forced vital capacity [FVC]) were measured before and at 15, 30, 60, and 90 minutes after two inhalations of full inspiratory reserve volume for each device. RESULTS: Both devices produced significant and similar bronchodilation. Mean FEV1 increased 32% above baseline 60 minutes after use of Autohaler and 31% after use of a standard MDI. Similar changes were noted in FEF25-75 and FVC for the two devices. Differences between devices for all spirometric variables were not statistically significant. CONCLUSION: Autohaler provides a promising alternative to the standard MDI by overcoming breath-hand discoordination.

Adolescent↗

High spatial resolution imaging of bone mineral using computed microtomography. Comparison with microradiography and undecalcified histologic sections.

RATIONALE AND OBJECTIVES: The application of various high-resolution (< 100 microns) imaging techniques for in vitro bone mineral analysis is explored. METHODS: The techniques of contact microradiography and microtomography, using the x-ray spectrum filtered out of synchrotron radiation (SR) and conventional staining techniques, are compared to each other by presenting a variety of different samples. The relationship between radiation exposure and spatial resolution micro-computed tomography (CT) images of a finger bone is explored. The relevant properties of SR are explained. RESULTS: In CT images, a spatial resolution of 100 microns was obtained. New bone mineral induced by mechanical periosteal irritation in a rabbit tibia was quantified. In one case a microradiogram and a microtomogram of the same slice were taken for comparison. Histologic sections and microradiograms taken from a specimen of a human femur for comparison are presented. CONCLUSIONS: Microradiography and staining techniques require rather sophisticated sample preparation; quantitative image analysis is more difficult as the resulting image must be digitized. The CT technique requires almost no sample preparation and allows for accurate bone mineral quantification. However, CT images with a resolution of several microns limit the sample size to a few mm. Micro-CT and microradiography can be performed with conventional x-ray sources, but the use of SR is of particular interest in high resolution imaging, because its white spectrum allows for optimum x-ray energy selection and its high intensity for short scan times.

Absorptiometry, Photon↗

Structure of the rat aromatic L-amino acid decarboxylase gene: evidence for an alternative promoter usage.

Aromatic L-amino acid decarboxylase catalyzes the biosynthesis of the neurotransmitters dopamine and serotonin. This enzyme is also expressed in nonneuronal tissues. Two reported cDNA sequences show that the pheochromocytoma message differs from the liver message only at the 5' untranslated region. We present the complete exonal organization and promoter sequences of the rat gene encoding this enzyme. The rat aromatic L-amino acid decarboxylase gene is composed of two promoters and 16 exons spanning more than 80 kb in the genome. The first exon carries the majority of the 5' untranslated sequence of the liver cDNA, and the second exon carries that of the pheochromocytoma cDNA. In the third exon, there are two alternatively utilized splicing acceptors specific to the first and second exons. Therefore, both alternative promoter usage and alternative splicing are operative for the differential expression of this gene. The sequence of each promoter region shows putative binding sites for octamer factors and AP-2.

Animals↗

Ease-of-use study of pirbuterol acetate in the Autohaler actuator in three countries: the United States, Germany, and France.

The preferred form of acute bronchodilator therapy is to administer aerosolized beta-agonist by a metered-dose inhaler. Many patients cannot use this device efficiently, the major problem being coordination of dose release with inspiration. A new breath-actuated inhaler (the Autohaler actuator) has been developed to overcome this problem. The objective of this study was to evaluate patient's and staff's perceptions of this device. Ninety-eight percent of patients rated the device easy to use and 83% rated the overall use as excellent or good. The staffs rated it as excellent or good for 93% of patients. It was concluded that patients would accept this device, and greater patient compliance could be realized.

Adult↗